Journal of Obstetrics and Gynaecology Research

Zimberelimab combined with systemic therapy extended tumor control in post‐radiotherapy cervical cancer with brain metastases: A case report

AbstractOut of the total cases of cervical cancer, brain metastases (BMs) are relatively rare, with an estimated incidence rate of 0.63% (range: 0.1%–2.2%). Additionally, BMs prognosis remains poor, and the average patient survival time following a BM diagnosis is 3 to 5 months. Few studies have addressed the effect of programmed cell death‐1 inhibitors against BMs in cervical cancer, although they are an established option for recurrent/metastatic disease. Hence, we report a case involving a 54‐year‐old post‐surgery patient with cervical cancer with a body mass index of 19.5 kg/m2 and Eastern Collaborative Oncology Group (ECOG) performance status of 3; the disease recurred with BMs 1 year later. Intensity‐modulated radiation therapy concurrent with temozolomide and bevacizumab was initiated, following which zimberelimab immunotherapy combined with anlotinib was administered to extend tumor control. The patient had a progression‐free survival duration of 10 months, the tumor response was assessed as a partial response based on the evaluation criteria for solid tumors (RECIST1.1), and the ECOG status improved to 1 after therapy. These findings suggest that immunotherapy‐based combination therapy following radiotherapy may be a good choice for patients with cervical cancer and BMs.

Impact of obesity on surgical and oncologic outcomes in patients with endometrial cancer treated with a robotic approach

AbstractAimThe surgical treatment of endometrial cancer (EC) can be more complicated in obese patients. Robotic surgery could simplify the surgical approach in these patients. The aim of our study was to compare the outcomes of robotic surgery in obese (body mass index ≥30 kg/m2) and nonobese patients.MethodsWe performed a retrospective study on patients with EC benefitting from a robotic approach in our institution. The primary outcome was the 5‐year overall survival (OS). We also assessed the 5‐year recurrence‐free survival (RFS), type of surgery, laparotomy conversion rate, adjuvant treatment and postoperative morbidity.ResultsWe analyzed 175 consecutive patients with EC who underwent robotic surgery, 42 patients with obesity and 133 patients without. The median follow‐up length was 37 months [1–120]. The OS rate was 97% in the whole population and the RFS was 74%. Obesity did not impact prognosis. Laparotomy conversion rate was low in both groups (5% in patients with obesity vs 3%, P = 0.619). There were no significant differences in terms of postoperative complications (5 vs 9%, P = 0.738). There were significantly less pelvic lymphadenectomies in patients with obesity (5 vs 12%, P = 0.005). In the subgroup of patients with high‐risk EC, rate of lymphadenectomy and of adjuvant treatments did not differ between patients with or without obesity.ConclusionObese patients with EC can be safely treated with a robotic approach, with a low complication rate and similar oncological outcomes compared to nonobese patients.

The giant steps in surgical downsizing toward a personalized treatment of vulvar cancer

AbstractThe present article aims to highlight the importance of changes of personalized surgical treatment for vulvar cancer. Current international literature regarding surgical treatment of vulvar cancer was evaluated. This included several studies and systematic reviews. Radical surgery approach, such as en bloc resection, was the first therapeutic option and the standard care for many years, even if burdened with a high complication rate and frequently disfiguring. Taussing and Way introduced radical vulvectomy approach with en bloc bilateral inguinal‐femoral lymphadenectomy; modified radical vulvectomy was developed, with a wide radical excision of the primary tumor. The role of inguinofemoral lymphadenectomy (mono or bilateral) changed in the years too, particularly with the advent of SLN biopsy as minimally invasive surgical approach for lymph node staging, in patients with unifocal cancer <4 cm, without suspicious groin nodes. More personalized and conservative surgical approach, consisting of wide local or wide radical excisions, is necessary to reduce complications as lymphedema or sexual disfunction. The optimal surgical management of vulvar cancer needs to consider dimensions, staging, depth of invasion, presence of carcinoma at the surgical margins of resection and grading, with the goal of making the treatment as individualized as possible.

Oral retinoid, acitretin, is effective in the management of resistant recurrent vulval verrucous carcinoma: A case report

AbstractVerrucous carcinomas are a rare variant of squamous cell carcinoma. Vulval verrucous carcinoma comprises only 1% of vulval malignancies. This case report discusses the successful management of aggressive recurrent vulval verrucous carcinoma with acitretin, an oral synthetic retinoid used to manage severe psoriasis, after multiple surgical interventions and radiotherapy had failed. This is the first reported case in which verrucous carcinoma had recurred in a musculocutaneous graft. To manage the recurrence, the patient underwent radiotherapy, which did not resolve the condition. The patient was then administered acitretin 25 mg once daily, which successfully resolved the condition, and the patient has been symptom free for 6 months. This report aims to propose the use of acitretin as a management option for recurrent verrucous carcinomas.

Effects of pretreatment radiological and pathological lymph node statuses on prognosis in patients with ovarian cancer who underwent interval debulking surgery with lymphadenectomy following neoadjuvant chemotherapy

AbstractAimTo analyze whether radiological and pathological lymph node statuses affected prognosis in patients with epithelial ovarian cancer who underwent neoadjuvant chemotherapy followed by interval debulking surgery.MethodsIn total, 82 patients undergoing interval debulking surgery, including systematic retroperitoneal lymphadenectomy, were eligible for this study. We retrospectively analyzed the association among radiological diagnosed retroperitoneal lymphadenopathy by computed tomographic scan before (rLN) and after (yrLN) neoadjuvant chemotherapy, pathological lymph node metastasis (pLN) and prognosis. Patient survival distribution was calculated using the Kaplan–Meier method.ResultsThere were 36 rLN+ cases (44%); there were no significant differences between rLN+ and rLN− with respect to progression‐free survival and overall survival. Progression‐free survival and overall survival did not differ between yrLN+ cases and yrLN− cases. Thirty‐nine cases (47.5%) were pLN+, and both progression‐free survival and overall survival were significantly shorter in pLN+ cases than in pLN− cases (P < 0.001 and P = 0.004, respectively). In univariate analysis, FIGO stage, pLN and surgical completion were prognostic factors for overall survival. Moreover, in multivariate analysis, pLN+ was the independent prognostic factor for progression‐free survival (P = 0.001, 95% confidence interval: 1.911–15.69), and pLN and surgical completion were the only independent prognostic factors for overall survival (P = 0.046, P = 0.012).ConclusionRadiological lymph node status may not be a prognostic factor in patients with ovarian cancer who underwent neoadjuvant chemotherapy followed by interval debulking surgery. Pathological lymph node metastasis affects progression‐free survival and overall survival.

Preoperative Magnetic Resonance Imaging versus Intraoperative Frozen Section Diagnosis for Predicting the Deep Myometrial Invasion in Endometrial Cancer: Our Experience and Literature Review

AbstractAimThe present study was designed to directly compare the diagnostic performance of preoperative magnetic resonance imaging (MRI) and intraoperative frozen section (FS) diagnoses in predicting deep myometrial invasion (MI) of endometrial cancer.MethodsUsing MRI findings and FS diagnoses, 194 patients with surgically staged endometrial cancer were evaluated for deep MI between 2006 and 2018. Definitive histological diagnosis of paraffin sections of excised tissues was used as the gold standard approach.ResultsOf 194 cases, 53 (27.3%) cases were finally diagnosed as having deep MI (≥50%). There was 82% total agreement between MRI and FS diagnoses in predicting deep MI, with a kappa value of 0.54 (95% confidence interval [CI] = 0.40–0.67, moderate agreement). The sensitivity of FS diagnosis (0.66, 95% CI = 0.52–0.78) for predicting deep MI was lower than that of MRI (0.77, 95% CI = 0.63–0.87; p = 0.21), while the specificity of FS (0.98, 95% CI = 0.93–0.99) was significantly higher than that of MRI (0.88, 95% CI = 0.81–0.93; p = 0.001). Overall, the accuracy of FS (0.89, 95% CI = 0.84–0.93) was higher than that of MRI (0.85, 95% CI = 0.79–0.90), although the difference did not reach statistical significance (p = 0.23). The accuracy (0.95, 95% CI = 0.90–0.97) was very high in cases with concordant MRI and FS results.ConclusionsMRI and FS showed different diagnostic characteristics for predicting deep MI, with a higher specificity observed for FS and the greatest accuracy obtained in concordant cases. Thus, our findings recommend the addition of FS diagnosis, either alone or in conjunction with MRI, to MI evaluation.

Health outcomes in women attending with clinical guideline PROGYNE to a primary care center for cervical cancer prevention

AbstractAimThe objective of the current study was to analyze the health outcomes of women attending with a clinical guideline to consultations for cervical cancer (CC) prevention in a primary care center.MethodsA cross‐sectional design was used, and data were collected from March to July 2016 with a sample of 87 women in Fortaleza, Brazil.ResultsThe following correlations were found: previous history of sexually transmitted infection (p = 0.025), women who used oral contraceptives (p = 0.035), and undergo the Papanicolaou test annually; having black skin color (p = 0.031) and attending to the first gynecological consultation; being single (p = 0.031), family history of cancer (p < 0.001), and undergoing the first Papanicolaou test within the first 3 years of sexual activity; age up to 30 years and positive colposcopy (p = 0.027); and being single and positive colposcopy (p = 0.021). CC was characterized by the presence of intraepithelial lesion detected on colposcopy (gold standard). Receiver operating characteristic curves were used to evaluate the diagnostic accuracy of visual inspection with Lugol's iodine, digital cervicography, and Papanicolaou test. The area under the curve values were as follows: digital cervicography: 0.558, p = 0.509; Lugol's iodine: 0.491, p = 0.919; and Papanicolaou test: 0.697, p = 0.024.ConclusionColposcopy in primary care provided a faster diagnosis of pre‐cancerous lesions. Understanding the health outcomes of women who underwent consultations for CC prevention, as well as the screening and diagnosis methods used, is essential to the service and national health system of the less developed countries.

Comparison of survival outcomes between laparoscopic surgery and abdominal surgery for radical hysterectomy as primary treatment in patients with stage IB2/IIA2 cervical cancer

AbstractObjectiveTo investigate the long‐term oncological outcomes of laparoscopic radical hysterectomy (LRH) and abdominal radical hysterectomy (ARH) for the treatment of stage IB2/IIA2 cervical cancer without preoperative adjuvant therapy.MethodsWe conducted a multicenter, retrospective, case‐matching study. The differences in overall survival (OS) and disease‐free survival (DFS) between the LRH and ARH were compared under the conditions of real‐world study and case–control matching (1:1 matching).ResultsThere was no significant difference in the outcomes of LRH (n = 580) and ARH (n = 1653) in 5‐year OS and DFS (OS: 80.6% vs. 86.1%, p = 0.421; DFS: 78.6% vs. 80.7%, p = 0.376). After 1:1 matching, there was no difference in 5‐year OS and DFS between LRH (n = 554) and ARH (n = 554) (OS: 80.4% vs. 84.5%, p = 0.993; DFS: 79.0% vs. 78.8%, p = 0.695). Before and after matching, the surgical approach was not an independent risk factor for 5‐year OS and DFS, and postoperative adjuvant therapy affected patient prognosis. Further subgroup analysis suggested that there was no difference in LRH (n = 313) and ARH (n = 1092) in 5‐year OS or DFS in patients who underwent standard postoperative adjuvant therapy (OS: 83.0% vs. 87.7%, p = 0.992; DFS: 79.0% vs. 82.5%, p = 0.323). After 1:1 pairing, the 5‐year OS and DFS in LRH (n = 295) and ARH (n = 295) showed no difference. Before and after matching, the surgical approach was not an independent risk factor affecting the 5‐year OS and DFS.ConclusionsThere was no difference in the oncological outcomes between laparoscopic and abdominal surgery in patients with stage IB2/IIA2 cervical cancer without preoperative adjuvant therapy.Clinical TrialsThe ethical approval number is NFEC‐2017‐135, and the clinical research registration number is CHiCTR1800017778 (International Clinical Trials Registry Platform Search Port, http://apps.who.int/trialsearch/).

Histological classification of uterine cervical adenocarcinomas: Its alteration and current status

AbstractAdenocarcinomas (ADCs) of the uterine cervix are relatively minor compared to squamous cell carcinomas. However, ADCs are histologically and histogenetically unique, especially because they can be with or without human papillomavirus (HPV) infection. At present, ADCs are divided into tumors as HPV‐associated ADCs (HA‐ADCs) and HPV‐independent ADCs (HI‐ADCs), including adenocarcinomas in situ (AIS) as their precursor, both of which consist of variable histological types. The usual‐type accounts for the majority of HA‐ADCs, and the gastric‐type is a representative of HI‐ADCs. Notably, it is clinicopathologically significant to differentiate between HA‐ADCs and HI‐ADCs because of the discrepancy in prognosis between them. Although relatively rare in comparison with HPV‐associated AIS (HA‐AIS), HPV‐independent AIS (HI‐AIS) has gradually attracted attention since gastric‐type ADC (g‐ADC) was introduced in the World Health Organization Classification 4th ed. (2014). Occasional HA‐ADCs and HI‐ADCs, including HA‐AIS and HI‐AIS, require p16 immunostaining, in situ hybridization, or HPV testing to differentiate between them because morphological features alone cannot often be conclusive for the diagnosis. A system focusing on the infiltrative pattern has been introduced due to its clinicopathological value. Staging criteria of HA‐ADCs with polypoid/exophytic growth, recommended by the International Collaboration on Cancer Reporting, may supplement the International Federation of Gynecology and Obstetrics staging system for clinical management and treatment.

LncRNA LINC00649 aggravates the progression of cervical cancer through sponging miR‐216a‐3p

AbstractAimIncreasing studies have revealed the participation of lncRNAs in the occurrence and development of cervical cancer. This study explored the influence of lncRNA LINC00649 in cervical cancer.MethodsExpression of LINC00649 and miR‐216a‐3p in cervical cancer was detected by reverse transcription quantitative real‐time polymerase chain reaction (RT‐qPCR). The Kaplan–Meier curve and Cox regression analyses were conducted to evaluate the clinical value of LINC00649 in cervical cancer. The roles of LINC00649 in cervical cancer cells were detected by transfecting siRNA through cellular function assays.ResultsLINC00649 expression was increased in cervical cancer tissues, especially in squamous histology, positive lymph node metastasis, and high‐FIGO stage tissues. The higher expression of LINC00649 predicted a shorter survival rate for patients. LINC00649 could bind directly with miR‐216a‐3p. Silence of LINC00649 could enhance the expression of miR‐216a‐3p and suppress the cervical cancer cell proliferation abilities, migration capacities, and invasion power. Whereas, transfection of miR‐216a‐3p inhibitor partially reverses the above cellular activities changes in cervical cancer cells.ConclusionsThe LINC00649 expression may act as a prognostic predictor and may aggravate cervical cancer progression by targeting miR‐216a‐3p, providing potential therapeutic targets for patients with cervical cancer.

Malignant struma ovarii: From case to analysis

AbstractAimTo evaluate the clinico‐pathologic features, treatment options, prognostic factors, and survival outcomes of malignant struma ovarii based on a systematic literature review in association with our case study.MethodsA systematic review of the medical literature was performed to identify articles about malignant struma ovarii from January 1983 until July 2020. We evaluated 178 cases.ResultsThe 5‐year progression‐free survival (PFS) and overall survival (OS) of the entire cohort was 72.5% and 91%, respectively. In univariate analysis, younger age (<43 years), whole strumal cyst diameter >95 mm, presence of a histologic type other than papillary classic‐type thyroid carcinoma within the tumor and lymphovascular space invasion were related to poor PFS. Patients who received radioactive iodine ablation (RIA) before the treatment failure had significantly higher PFS than those who did not receive RIA (94.9% vs. 64.8%, p = 0.041, respectively). In univariate analysis, PFS was significantly higher in patients who underwent gynecologic surgery followed by thyroidectomy and RIA compared with those who had surgical treatment only (94.5% vs. 64.3%, p = 0.05, respectively). However, this result could not be identified as an independent prognostic factor in multivariate analysis (p = 0.207). Younger age and absence of capsular involvement were related to significantly increased OS. Histologic type was the only independent prognostic factor for PFS (hazard ratio: 3.30, 95% confidence interval: 1.122–9.748; p = 0.030)ConclusionThe most common histologic subtype was the papillary classic type. The presence of a histologic type other than the classic papillary thyroid carcinoma within the tumor was an independent adverse prognostic factor.

A case of transient hyperthyroidism induced by placental site trophoblastic tumor

AbstractWe report a case of placental site trophoblastic tumor (PSTT) with transient hyperthyroidism. A 29‐year‐old gravida 2 para 2 woman presented with abnormal genital bleeding 6 months after delivery. Endometrial histology suggested PSTT. Serum human chorionic gonadotropin (hCG) was 117 mIU/mL and serum estradiol (E2) were 51 pg/mL. She reported increased appetite, sweating, fatigue, and 7‐kg weight loss within 3 months. Blood samples showed a thyroid‐stimulating hormone (TSH) level <0.01 μIU/mL, FT3: 24.3 pg/mL, FT4: 5.3 ng/mL. The patient was diagnosed with hyperthyroidism. After thyroid function normalized, laparoscopic hysterectomy and bilateral salpingectomy were performed. Two years postsurgery, there was no recurrence, and thyroid function improved. The hCG produced from gestational trophoblastic disease has stronger TSH activity than that from gestational trophoblasts. However, in PSTT, the E2 level, which increases thyroid‐binding proteins and suppresses elevated thyroid hormone levels, is low and may induce hyperthyroidism. In cases of suspected PSTT, thyroid function should be evaluated when hyperthyroid symptoms are present.

Regional Heterogeneity and Future Challenges in Ovarian Cancer Burden in Asia

ABSTRACT Background Ovarian cancer (OC) is a growing public health challenge in Asia, with rising incidence and regional disparities. Using the Global Burden of Disease (GBD) 2021 dataset, this study assessed temporal trends, spatial patterns, and determinants of OC burden in Asia from 1990 to 2021, with projections to 2036. Methods Data were extracted from GBD 2021 for all Asian regions. Three indicators were analyzed: age‐standardized incidence rate (ASIR), mortality rate (ASMR), and disability‐adjusted life years rate (ASDR). Trends were evaluated using estimated annual percentage change (EAPC) and Joinpoint regression. Decomposition analysis examined contributions of population aging, growth, and epidemiological shifts. Age–period–cohort (APC) analysis was performed to disentangle the effects of age, period, and cohort on OC incidence. Future burden (2022–2036) was projected with an autoregressive integrated moving average (ARIMA) model. Results From 1990 to 2021, OC burden increased markedly. Southeast, South, and Central Asia had the greatest rises in ASIR, ASMR, and ASDR, while East Asia and high‐income Asia Pacific showed stable or declining trends, likely due to healthcare advances and early detection. Higher sociodemographic index (SDI) correlated with greater incidence and mortality. Decomposition revealed aging as the main driver in East Asia and high‐income Asia Pacific, while population growth dominated in South Asia. APC analysis highlighted age as the primary risk factor, with a rising period effect and a declining cohort effect. ARIMA projections (2022–2036) show steady ASIR growth and U‐shaped trajectories (initial decline then rise) for ASMR and ASDR. Conclusion The increasing OC burden in Southeast, South, and Central Asia underscores the urgent need for region‐specific strategies. Interventions focusing on early diagnosis, equitable healthcare, and addressing demographic and epidemiological drivers are essential to mitigate the projected rise by 2036.

Underrecognized diagnostic discordance and delay in endometrial dedifferentiated and undifferentiated carcinoma

AbstractAimDedifferentiated and undifferentiated endometrial carcinoma (DC/UC) is a rare subtype of endometrial cancer characterized by undifferentiated carcinoma components. This study aimed to investigate diagnostic discrepancies and delays in DC/UC and compare them with low‐grade endometrioid carcinoma (LGEC).MethodsWe retrospectively analyzed 20 DC/UC and 40 LGEC cases finally diagnosed at our hospital (2016–2024). We compared the data of the two groups, including clinicopathologic characteristics and diagnostic intervals defined as the time from the date of initial biopsy to the date of definitive diagnosis. We assessed diagnostic discordances between preoperative diagnoses, including radiological, clinical, and biopsy, and final diagnoses with immunohistochemical analyses.ResultsDC/UC cases exhibited significantly longer diagnostic intervals (median 46 vs. 5 days, p = 0.037) and required more biopsy attempts (median two vs. 1, p = 0.002) and immunohistochemical tests (median 19 vs. 6, p = 0.001) than LGEC cases. In preoperative diagnoses, 60% of DC/UC cases showed diagnostic discrepancies. Radiological findings frequently suggested uterine sarcoma in DC/UC (30%, 6/20). Only 50% of DC/UC were suggested via initial biopsy. Immunohistochemistry revealed mismatch repair deficiency in 70% of DC/UC cases.ConclusionsFrequent diagnostic discrepancies and delays were observed in DC/UC, possibly due to its atypical imaging and histopathological features. Raising awareness of DC/UC's clinical and pathological characteristics is crucial to minimizing diagnostic delays. Given its frequency (at least 1% of endometrial cancers) and eligibility for emerging therapies, prioritizing DC/UC in differential diagnoses and improving diagnostic workflows through interdisciplinary collaboration are required for timely and effective treatment.

Psychosocial Burden of Women With Cervical Intraepithelial Neoplasia in Japan: Results of A Web‐Based Survey

ABSTRACT Aim Human papillomavirus (HPV) infection carries a high risk of developing cervical intraepithelial neoplasia (CIN) and cancer in women. For women with CIN, follow‐up examinations and treatment are necessary and pose a psychosocial burden. This study investigated the psychosocial burden among women with CIN in Japan. Methods This observational, cross‐sectional, online survey enrolled women aged 20–49 years in Japan who used a mobile health app (Kencom) linked to an employment‐based health insurance association database. Participants completed a screening questionnaire on cervical screening history and CIN status. Eligible women then completed the HPV Impact Profile (HIP) to assess their psychosocial burden. CIN status was confirmed using diagnostic codes recorded in the Kencom database. Results A total of 404 women were eligible for the study, comprising 121 with confirmed CIN and 283 without CIN. The baseline characteristics were similar, although women with CIN were slightly younger (39.8 vs. 41.5 years) and less likely to be married (55.4% vs. 70.0%). Women with CIN had significantly higher total HIP scores, indicating greater burden than those without CIN (42.2 vs. 24.5; p  < 0.001). The burden was evident in women with CIN grade 1 ( p  < 0.001) and more pronounced in younger women (trend for age groups; p  < 0.001). Conclusions This study is the first to report a significant psychosocial burden of CIN in Japan, irrespective of CIN severity, with a greater impact in younger women. This psychosocial burden can be alleviated by HPV vaccination with evidence of preventing CIN.

Bilateral adrenal metastases of endometrial cancer with adrenal insufficiency

AbstractAdrenal metastasis from endometrial cancer is extremely rare and has a poor prognosis, especially for bilateral adrenal metastases. It is usually asymptomatic without any adrenal hormonal abnormalities. A 50‐year‐old postmenopausal woman presented with acute right‐sided back pain and history of occasional abnormal uterine bleeding. She was diagnosed with endometrial cancer with ruptured bilateral adrenal metastases. She underwent total hysterectomy and bilateral salpingo‐oophorectomy, and the pathological findings revealed dedifferentiated carcinoma. After three courses of adjuvant chemotherapy, the bilateral adrenal metastases had increased in size, with worsening back pain and adrenal hormone insufficiency. The patient died 6 months after the identification of adrenal tumors. Acute back pain may lead to the identification of a ruptured adrenal metastasis. The possibility of gradual adrenal insufficiency should be considered in bilateral adrenal metastases. Although the prognosis is poor, tumor debulking surgery followed by adjuvant chemotherapy could be suggested to improve the prognosis.

Radical hysterectomy versus simple hysterectomy and brachytherapy for stage II endometrial cancer

AbstractPurposeTo compare the survival outcome between radical hysterectomy and simple hysterectomy with radiation therapy in patients with stage II endometrial cancer.Materials and MethodsThis is a retrospective cohort study based on the SEER database from January 1, 1988 to December 31, 2015.ResultsOf 577 patients were enrolled in the study, 117 patients received radical hysterectomy and 460 patients received simple hysterectomy combined with vaginal brachytherapy. All patients received external beam radiation therapy after the surgery. The median follow‐up duration was 82.77 ± 1.44 months. No differences were found on the baseline information between two groups. Both the 5‐year overall survival (62.31% vs. 78.48%, p < 0.001) and 5‐year cause‐specific survival (74.60 vs. 85.38%, p = 0.01) were shorter in radical hysterectomy than in simple hysterectomy combined with vaginal brachytherapy group. However, the positive outcomes were further validated in patients with high‐risk endometrial cancer, not in patients with grade 1–2 low‐risk endometrial cancer both on cause‐specific survival and overall survival. In patients with grade 3 low‐risk endometrial cancer, the tendency was only found with lower overall survival not cause‐specific survival.ConclusionsThis study revealed that in patients' high‐risk stage II endometrial cancer, radical hysterectomy was associated with shorter survival outcome than simple hysterectomy combined with vaginal brachytherapy.

Current state of management of struma ovarii and preoperative imaging features: A retrospective case series study of 18 patients at a single institution

AbstractAimEven though 95% of struma ovarii are benign, it is often overtreated because of the difficulty to distinguish it from malignancy. In this study, our aim was to evaluate the current state of the preoperative diagnosis and the selection of the surgical procedure, and to improve preoperative diagnostic accuracy by retrospectively reviewing imaging findings.MethodsWe retrospectively reviewed the clinical course and imaging characteristics of 18 patients who were diagnosed postoperatively with struma ovarii, pathologically, at our institution between 2015 and 2021.ResultsThe preoperative diagnoses included benign ovarian tumor in eight cases, borderline in four cases, and malignant in six cases. None of the cases were diagnosed as struma ovarii preoperatively. Of the seven patients who had confirmed a desire for future childbearing, four patients were suspected for borderline or malignant tumor preoperatively, and underwent abdominal adnexectomy. In patients without a desire for childbearing, laparoscopic surgery was performed in only 45% of the patients whose preoperative diagnosis was benign. On magnetic resonance imaging (MRI), 54% of the cases showed enhanced solid components, which is characteristic of malignant tumors, but diffusion restriction was observed in only 11%. On computed tomography (CT), 78% of the cases showed a high attenuation lesion reflecting thyroid tissue.ConclusionsStruma ovarii is difficult to distinguish from malignancy preoperatively, making the choice of surgical approach complicated. A comprehensive evaluation of diffusion‐weighted MRI and CT findings may improve the accuracy of preoperative diagnosis of struma ovarii.

Prognostic significance of co‐existent adenomyosis on outcomes and tumor characteristics of endometrial cancer: A meta‐analysis

AbstractObjectivePublished data on the impact of co‐existent adenomyosis on the prognosis of patients with endometrial cancer remains elusive, with studies reporting conflicting results. We conducted this meta‐analysis to evaluate the prognostic significance of co‐existent adenomyosis on clinical outcomes and tumor characteristics of endometrial cancer patients.MethodsA comprehensive literature review of multiple databases was conducted; quality assessment of eligible studies was performed by the Newcastle‐Ottawa scale (NOS). The outcomes of interest were compared in endometrial cancer patients with or without adenomyosis. Hazards ratios (HR) and Odds ratios (OR) with 95% confidence interval (CI) were calculated as a measure of effects.ResultsFourteen retrospective observational studies comprising 1308 endometrial cancer patients with adenomyosis and 3734 patients without adenomyosis were included in this meta‐analysis. Results indicated that endometrial cancer patients with adenomyosis was significantly associated with an increased overall survival rate (HR = 0.51; 95% CI = 0.38–0.69; P < 0.00001), but not with disease‐free survival rate (HR = 0.68; 95% CI = 0.30–1.53; P = 0.35); besides, significantly associated with decreased ratio of deep myometrial invasion (OR = 0.45; 95% CI = 0.33–0.60; P < 0.00001), lymphovascular space invasion (OR = 0.44; 95% CI = 0.29–0.68; P = 0.0002), an increased ratio of histological grade 1 (OR = 1.84; 95% CI = 1.34–2.53; P = 0.0002) and FIGO I‐II (OR = 1.85; 95% CI = 1.49–2.30; P < 0.00001). However, there was no significant difference in pathological type and lymph node metastasis. There was a low to high heterogeneity with I2 ranging from 0 to 67%.ConclusionThis meta‐analysis indicated that co‐existent adenomyosis with endometrial cancer is associated with favorable tumor characteristics and could serve as a potential protective factor for the prognosis of endometrial cancer.

Tumor growth direction predicts surgical difficulty in large uterine fibroids: A retrospective imaging‐based study

Abstract Objective To identify preoperative imaging features associated with retroperitoneal growth of large uterine fibroids and evaluate their impact on surgical outcomes. Methods This retrospective study included 20 patients who underwent hysterectomy for uterine fibroids measuring ≥10 cm between 2014 and 2024. Preoperative CT or MRI was evaluated for four features: bladder displacement, sigmoid colon deviation, cecal displacement, and hydronephrosis. Tumor growth direction (intraperitoneal vs. retroperitoneal) was determined intraoperatively. Operative time, blood loss, and complications were compared between groups. Results Eight tumors exhibited retroperitoneal growth. Bladder displacement, cecal shift, sigmoid colon deviation, and hydronephrosis were significantly more common in retroperitoneal cases (all p  < 0.05). Retroperitoneal tumors were associated with significantly greater median blood loss (1591 mL vs. 651 mL, p  = 0.043), although operative time did not differ significantly (301 vs. 232 min, p  = 0.237). Organ injury or resection occurred only in the retroperitoneal group. A bubble plot illustrated the trend of increased surgical burden in retroperitoneal cases. Conclusion Retroperitoneal growth of large uterine fibroids is associated with increased intraoperative blood loss and surgical complexity. Four simple imaging features may serve as reliable indicators of growth direction and help guide preoperative planning.

Carcinogenesis and epidemiology of cervical cancer: The hallmark of human papillomavirus‐associated cancer

AbstractCervical cancer affects women worldwide and is the most common human papillomavirus (HPV)‐associated cancer. Carcinogenesis caused by HPV results in specific cancer behavior because of the underlying viral infection. The mechanism and timing of the transformation from viral infection to cancer cells have been elucidated in detail. Treatments for this cancer are based on its characteristics and are being implemented. Moreover, HPV infection is widespread worldwide and is transmitted through sexual activity. Although the HPV vaccination is the most effective strategy of preventing cervical cancer, it is not feasible to vaccinate the entire human population especially in low‐ and middle‐income countries. In order to consider the next step for HPV vaccination, we need to understand the characteristics of HPV carcinogenesis and cervical cancer. Additionally, treatment aimed at preservation of reproductive function in patients with cervical cancer is often required, as the cervix is a reproductive organ and because the disease is more prevalent in the adolescent and young adult generation. Thus, there are still many challenges in the diagnosis, treatment, and prevention of cervical cancer.

Thermocoagulation versus cryotherapy for the treatment of cervical precancers

AbstractAimTo compare thermocoagulation and cryotherapy for treatment of high‐grade cervical intraepithelial neoplasia (CIN).MethodsFrom May 2017 to May 2018, women with CIN2/3 were randomized to thermocoagulation or cryotherapy at Peking University Shenzhen Hospital. Follow‐up at 4 and 8 months included cytology and human papillomavirus (HPV) testing. Women who were HPV‐positive or had atypical squamous cells of undetermined significance or higher‐grade disease underwent colposcopy/biopsy.ResultsAmong 149 women enrolled, 74 were randomized to thermocoagulation, and 75 to cryotherapy (excluded four were immediately referred for thermocoagulation due to large lesions). At follow‐up, there was no difference between the thermocoagulation and cryotherapy groups in HPV‐negative (4/8 months: 72.5%/86.2% vs 68.6%/80.6%) and pathology‐negative (97.1%/98.5% vs 94.3%/92.3%) rates (all P > 0.05). The cytology‐negative rate was similar for thermocoagulation and cryotherapy at 4 months (79.7% vs 78.9%, P > 0.05), but higher for thermocoagulation at 8 months (100% vs 88.7%, P < 0.05). No lesions were observed among the four referral women at follow‐up. As compared with cryotherapy, thermocoagulation was associated with shorter duration of treatment and less vaginal discharge, but higher pain during application and longer bleeding after treatment.ConclusionThermocoagulation was as effective and safe as cryotherapy and might be easily applied to treat high‐grade cervical lesions.

Impact of Prolonged Surgical Waiting Time on 5‐Year Progression‐Free Survival in Patients With Endometrial Cancer

ABSTRACT Aim To evaluate the impact of surgical waiting time (SWT) on 5‐year progression‐free survival (PFS). Secondary objectives were to evaluate 5‐year overall survival (OS) and prognostic factors for recurrence and OS in endometrial cancer (EC), considering Thailand's Key Performance Indicator (KPI) recommending surgery within 4 weeks. Methods This retrospective cohort study included 377 patients with histologically confirmed EC who underwent primary surgery at Hatyai Hospital between October 2016 and September 2024. SWT was defined as the time from diagnostic biopsy to definitive surgery and categorized as early (≤ 4 weeks) or delayed (> 4 weeks). Survival outcomes were assessed using Kaplan–Meier curves and log‐rank tests. Prognostic factors were analyzed using Cox proportional hazards models. Results The median SWT was 32 days. Median follow‐up was 23 months. Delayed surgery correlated with higher BMI, larger tumors, and increased recurrence (12.7% vs. 4.9%, p  = 0.010). Advanced FIGO stage, non‐endometrioid histology, grade 3 tumors, LVSI, and delayed SWT were significant recurrence risk factors. Multivariate analysis confirmed advanced stage (HR: 5.15, p  < 0.001) and SWT > 4 weeks (HR: 3.22, p  = 0.011) as independent predictors. Recurrence risk increased with longer delays (> 6 weeks: HR: 3.22; > 8 weeks: HR: 3.16). Kaplan–Meier curves showed significantly reduced PFS with prolonged SWT, while its effect on 5‐year OS was not significant ( p  = 0.1). Conclusions Surgical delays beyond 4 weeks were associated with reduced PFS and increased recurrence, supporting Thailand's KPI and underscores the importance of timely surgery. The short follow‐up may limit interpretation of long‐term outcomes. Longer follow‐up is warranted to confirm these results.

Endometrial stromal sarcoma: A review of rare mesenchymal uterine neoplasm

AbstractObjectiveThis review aims to analyze the pathological aspects, diagnosis and treatment of rare mesenchymal uterine tumors.MethodsOn August 2019, a systematic review of the literature was done on Pubmed, MEDLINE, Scopus, and Google Scholar search engines. The systematic review was carried out in agreement with the Preferred Reporting Items for Systematic Reviews and Meta‐Analyzes statement (PRISMA). The following words and key phrases have been searched: “endometrial stromal sarcoma”, “low‐grade endometrial stromal sarcoma”, “high‐grade endometrial stromal sarcoma”, “uterine sarcoma”, “mesenchymal uterine tumors” and “uterine stromal sarcoma”. Across these platforms and research studies, five main aspects were analyzed: the biological characteristics of the neoplasms, the number of cases, the different therapeutic approaches used, the follow‐up and the oncological outcomes.ResultsOf the 94 studies initially identified, 55 were chosen selecting articles focusing on endometrial stromal sarcoma. Of these fifty‐five studies, 46 were retrospective in design, 7 were reviews and 2 randomized phases III trials.ConclusionEndometrial stromal sarcomas are rare mesenchymal uterine neoplasms and surgery represents the standard treatment. For uterus‐limited disease, the remove en bloc with an intact resection of the tumor (without the use of morcellation) is strongly recommended. For advanced‐stage disease, the standard surgical treatment is adequate cytoreduction with metastatectomy. Pelvic and para‐aortic lymphadenectomy is not recommended in patients with Low‐grade Endometrial Stromal Sarcoma (ESS), while is not clear whether cytoreduction of advanced tumors improves patient survival in High‐grade ESS. Administration of adjuvant radiotherapy or chemotherapy is not routinely used and its role is still debated.

Positive peritoneal cytology is an independent risk factor in endometrial cancer

AbstractObjectiveWe aimed to investigate whether positive peritoneal cytology could serve as a prognostic factor in endometrial cancer (EC).MethodsFrom patients with EC surgically treated at Peking University People's Hospital between 2006 and 2016, 520 patients were selected for retrospective investigation. Clinical and pathologic factors associated with positive peritoneal cytology were assessed using univariate and multivariate logistic regressions model. Disease‐free survival (DFS) and overall survival (OS) were evaluated using Kaplan–Meier estimation and multivariate Cox regressions model.Results(i) The incidence of positive peritoneal cytology in EC patients was 9.0% (47/520). (ii) Multivariate analysis showed that the independent risk factors of positive peritoneal cytology were nonendometrioid carcinoma (odds ratio [OR] = 4.0, 95% confidence interval [CI], 1.8–8.8, P = 0.001), tumor diameter ≥2 cm (OR = 3.2, 95% CI, 1.2–8.7, P = 0.023), cervical stromal invasion (OR = 2.9, 95% CI, 1.3–6.6, P = 0.009) and distant metastasis (OR = 6.5, 95% CI, 1.7–25.4, P = 0.007). (iii) The 5‐year DFS and 5‐year OS of the positive peritoneal cytology group were significantly lower compared with the negative group (54.0% vs 93.2%, P < 0.001; 63.6% vs 94.6%, P < 0.001). (iv) After other contributing factors were adjusted in the multivariable model, positive peritoneal cytology remained an independent predictor of decreased DFS (OR = 2.8, 95% CI, 1.3–6.0, P = 0.007) and OS (OR = 2.8, 95% CI, 1.0–7.2, P = 0.035).ConclusionPositive peritoneal cytology was an independent risk factor in EC patients. Even though it is no longer an indicator according to the current International Federation of Gynecology and Obstetrics staging system, the peritoneal cytology status should still be considered for accurate risk stratification in EC.

Choice for prophylactic antibiotics: Cefazolin plus metronidazole or cefoxitin alone for endometrial cancer surgical staging

AbstractAimThe use of prophylactic antibiotics has greatly reduced the incidence of surgical site infections after hysterectomy. It is worth discussing which antibiotic is better. The purpose of this study was to investigate the role of the combined utilization of cefazolin and metronidazole for the prevention of surgical site infection in laparoscopic staging surgery of endometrial cancer.MethodsA retrospective analysis was performed on the incidence of surgical site infection in patients with endometrial cancer who underwent laparoscopic surgical staging from January 2000 to June 2019 within 1 month after surgery. Logistic regression model was used for univariate and multivariate analysis.ResultsA total of 1783 patients were included in this study, of which 641 were treated with cefazoline plus metronidazole (group 1) as a prophylactic antibiotic, while the other 1142 were treated with cefoxitin (group 2). There was no difference in clinical characteristics between the two groups. The rates of surgical site infection in groups 1 and 2 were 3.6% (n = 23) and 5.7% (n = 65), respectively. The most common site of infections was vaginal, with the incidence of 1.7% (n = 11) and 3.3% (n = 38) in groups 1 and 2, respectively. The multivariate analysis disclosed that cefazoline plus metronidazole significantly reduced the incidence of surgical site infections compared with cefoxitin (logistic, odds ratio = 2.213, 95% confidence interval 1.193 to 4.107).ConclusionCefazolin plus metronidazole as prophylactic antibiotics for surgical staging of endometrial cancer can more effectively reduce the incidence of surgical site infections than cefoxitin.

Assessment of thiol disulfide balance in early‐stage endometrial cancer

AbstractAimWe carried out this research to assess thiol disulfide balance in patients with early‐stage endometrial cancer.MethodsFifty‐seven endometrial cancer patients and 60 age‐matched healthy subjects volunteered for this study. Thiol disulfide parameters and the ratios of these parameters were examined using a colorimetric system. We also evaluated total antioxidant capacity, total oxidant capacity and oxidative stress index.ResultsSubjects with endometrial cancer had statistically significantly lower serum native thiol and total thiol levels (224.2 [122.8–267.5] and 270.5 [171.6–323.2], respectively) than healthy subjects (281.35 [213.45–358.9] and 339.55 [274.1–425.95], respectively) (P = 0.001, P < 0.001). Subjects with endometrial cancer had statistically significantly higher serum disulfide/native thiol and disulfide/total thiol ratios (12.22 [8.77–17.61] and 9.82 [7.46–13.02], respectively) than healthy subjects (8.9 [6.79–16.35] and 7.36 [5.9–12.32], respectively) (P = 0.038, P = 0.028). Disulfide/native thiol ratio appeared to be strongly and positively correlated with the stage of endometrial cancer (r = 0.827, P < 0.001).ConclusionThis is an initial report related to thiol disulfide balance in endometrial cancer patients. We believe that oxidative stress contributes both to the evolution and to the progression of the disease. We conclude that deterioration of thiol disulfide balance due to oxidative stress is likely to contribute to the etiopathogenesis of endometrial cancer.

New therapeutic approaches for the fertility‐sparing treatment of endometrial cancer

AbstractThis review seeks to describe new fertility‐sparing endometrial cancer (EC) treatment strategies that take into consideration the medical and general health background of patients. We particularly focus on the application of metformin, which is a biguanide widely prescribed for treatment of type 2 diabetes mellitus. Fertility‐sparing treatment using progestin is considered a standard treatment option for patients with atypical endometrial hyperplasia (AEH) and EC who desire to conceive. A previous meta‐analysis of fertility‐sparing treatments revealed a high remission rate; however, high rates of relapse persisted. Most young patients with AEH and EC who are subjected to fertility‐sparing treatment have a background of obesity, insulin resistance and abnormal glucose tolerance complicated with polycystic ovary syndrome. Recently, metformin has been attracting more attention in the field of cancer research. Several in vitro and in vivo reports regarding the efficacy of metformin in EC management have accumulated. Thus far, the efficacy of combining metformin with progestin has been revealed in a single phase II study of medroxyprogesterone acetate in combination with metformin as a fertility‐sparing treatment for patients with AEH or EC. In addition to improving the metabolic profile of patients with EC having metabolic disorders, metformin supplementation may improve the long‐term oncological outcome of these patients. To date, many clinical trials employing progestin and metformin as a fertility‐sparing treatment of AEH and EC are ongoing. In the near future, it is expected that the clinical advantage of metformin progestin combination therapy will be clarified.

Olaparib maintenance therapy for recurrent adult granulosa cell tumors: A case report

Abstract Poly (ADP‐ribose) polymerase inhibitors (PARPi) are now available for advanced or recurrent epithelial ovarian cancer after platinum‐based chemotherapy; however, there is little known concerning the use of PARPi for adult granulosa cell tumors (AGCT). A 49‐year‐old woman, who previously had primary debulking surgery and a second surgery for a first intraperitoneal recurrence, received a surgery for a second intraperitoneal recurrence of AGCT. Although she received paclitaxel–carboplatin combination chemotherapy and a combination of bleomycin, etoposide, and cisplatin after the surgeries for the first and the second recurrences, respectively, the risk of a third recurrence was considered very high due to microscopic peritoneal dissemination. Olaparib administration was initiated based on a FANCA mutation, which results in homologous recombination deficiency. The patient has been recurrence‐free for over 4 years since the initiation of olaparib. This case highlights the possibility of using olaparib for AGCT with a homologous recombination gene mutation.

Impact of tumor necrosis factor‐alpha and lysophosphatidic acid on the behavior of ovarian cancer cells in a three‐dimensional collagen hydrogel

Abstract Background Advanced ovarian cancer involves tumor cells proliferating within ascitic fluid, which is rich in chemokines, cytokines, growth factors, and phospholipids essential for tumor progression. Tumor necrosis factor‐alpha (TNF‐α) and lysophosphatidic acid (LPA) are critical components that modulate ovarian tumor cell behavior in vivo, though most in vitro studies have relied on cell monolayers that do not accurately represent the tumor microenvironment. We thus investigated TNF‐α and LPA effects on ovarian tumor cells cultured in collagen scaffolds, which are a model more reflective of in vivo conditions. Methods Ovarian cancer cell lines SKOV‐3, OVCAR‐8, OVCAR‐5, and OVCAR‐4 were cultured in collagen I hydrogels at various concentrations of TNF‐α and LPA for 2–8 days. Outcomes included cell morphology, collagen topography, secretion of vascular endothelial growth factor (VEGF), interleukin‐8 (IL‐8), interleukin‐6 (IL‐6), and cell survival endpoints, with comparisons to collagen topography observed in ovarian tumor tissue. Results Collagen I fiber topography in 3D hydrogels remodeled over time, resembling the ovarian cancer tissue. LPA significantly reduced hydrogel size in SKOV‐3 cells. While LPA modestly altered VEGF secretion, both LPA and TNF‐α increased IL‐8 secretion over time, with TNF‐α also elevating IL‐6 levels. TNF‐α reduced cell survival in OVCAR‐8 and OVCAR‐5, while LPA promoted cell growth in SKOV‐3, OVCAR‐8, and OVCAR‐5. Conclusions TNF‐α and LPA have diverse, cell line‐specific effects on ovarian cancer cells in collagen hydrogels, underscoring cell line heterogeneity and the utility of 3D models.

Sertoli cell tumor associated with ovarian sex cord tumor with annular tubules in a patient with 46 XY disorder of sex development and 9p24.3 deletion, case report

Abstract We report a rare case involving a 22‐year‐old phenotypically female patient who presented to our care with primary amenorrhea and spontaneous breast development. Hormonal analysis indicated hypergonadotropic hypogonadism, and imaging revealed a hypoplastic uterus and calcified ovaries. Karyotyping was 46, XY and the presence of the SRY gene was confirmed. The patient underwent laparoscopic bilateral salpingo‐oophorectomy due to the high risk of malignancy development. Histopathological analysis revealed bilateral Sertoli cell tumors and a sex cord tumor with annular tubules in the right gonad. Next generation sequencing genetic testing identified a 1.24 Mb deletion on chromosome 9p24.3, which included the DMRT1, DMRT2, and DMRT3 genes, as well as a partial deletion of KANK1. Hormonal replacement therapy was not initiated due to the potential risk of tumor recurrence, and follow‐up imaging was scheduled every 6 months for the first 2 years and then annually. No recurrence was observed at 24 months.

A case of ovarian carcinosarcoma with germline BRCA2 pathogenic variant

AbstractOvarian carcinosarcoma in hereditary breast and ovarian cancer syndrome is rare. A 43‐year‐old woman with a family history of prostate and uterine or ovarian cancer had an 8‐cm mass in the right ovary. Although computed tomography suggested peritoneal dissemination to the Douglas pouch, she wanted to preserve her fertility; therefore, she underwent a right salpingo‐oophorectomy. Histopathological diagnosis was carcinosarcoma consisting of high‐grade serous carcinoma and sarcomatous components, including cartilage. Three weeks later, she underwent radical surgery. The disease was classified as advanced stage IIIB (FIGO 2014). A germline BRCA2 pathogenic variant was identified. After postoperative adjuvant chemotherapy, maintenance therapy with a poly(adenosine diphosphate‐ribose) polymerase (PARP) inhibitor was continued for 25 months without recurrence. A detailed examination of a mass in her left breast at her first visit revealed a ductal carcinoma in situ. PARP inhibitors may be effective as maintenance therapy for advanced ovarian carcinosarcoma with germline BRCA mutations.

Assessment of tissue factor pathway inhibitor 2 (TFPI2) as a novel serum marker for malignant tumors of the ovary before and after treatment: A case‐control study

AbstractAimTissue factor pathway inhibitor 2 (TFPI2) is a preoperative biomarker that was developed to discriminate ovarian benign tumors from cancer and is covered by health insurance in Japan. The purpose of this study was to evaluate how the TFPI2 changes after treatment.MethodsSerum levels of TFPI2 (cut off 191 pg/mL) and CA125 (cut off 35 U/mL) before and after primary debulking surgery in patients with ovarian malignant tumors were evaluated among recurrent and nonrecurrent cases, respectively.ResultsA total of 46 cases were analyzed, including 11 borderline tumors, 13 clear cell carcinomas, 15 serous carcinomas, 4 endometrioid carcinomas, and 3 mucinous carcinomas. Among 37 patients without recurrence, the preoperative mean levels of TFPI2 (235.3 pg/mL, range: 78.3–607.7) and CA125 (1125.5 U/mL, range: 6.2–6272.0) were higher than the cutoff values. The mean minimum level of TFPI2 decreased to below the cutoff (150.2 pg/mL, range 56.4–471.1) at 3 months or more after primary debulking surgeries. The postoperative TFPI2 level exceeded the cutoff in 11 out of 37 patients without recurrence (29.7%); however, the postoperative TFPI2 level decreased in 8 patients. The mean maximum levels of TFPI2 and CA125 in 9 patients after recurrence were 492.6 pg/mL and 727.4 U/mL, respectively. Moreover, the mean TFPI2 level was higher than the preoperative one (421.5 pg/mL), different from CA125 (2903.8 U/mL).ConclusionsOur results suggest the clinical validity of TFPI2 as a serum tumor marker for postoperative recurrence screening among malignant ovarian tumors.

Transvaginal natural orifice transluminal endoscopic surgery hysterectomy in patients with body mass index >50: An Asian experience

AbstractWe present two cases of patients with body mass index (BMI) >50 undergoing transvaginal natural orifice transluminal endoscopic surgery (vNOTES) hysterectomy for gynecological indications. Case 1 involves a 52‐year‐old woman with post‐menopausal bleeding and suspicion of ovarian torsion, while case 2 describes a patient with newly diagnosed endometrial adenocarcinoma. Both cases highlight the feasibility and challenges of vNOTES in this patient population. To date, this is the first paper to describe the use of vNOTES in patients of Asian ethnicity, with BMI >50.

The current state and future perspectives of radiotherapy for cervical cancer

AbstractRadiotherapy is an effective treatment method for cervical cancer and is typically administered as external beam radiotherapy followed by intracavitary brachytherapy. In Japan, center shielding is used in external beam radiotherapy to shorten treatment time and reduce the doses delivered to the rectum or bladder. However, it has several challenges, such as uncertainties in calculating the cumulative dose. Recently, external beam radiotherapy has been increasingly performed with intensity‐modulated radiotherapy, which reduces doses to the rectum or bladder without center shielding. In highly conformal radiotherapy, uncertainties in treatment delivery, such as inter‐fractional anatomical structure movements, affect treatment outcomes; therefore, image‐guided radiotherapy is essential for appropriate and safe performance. Regarding intracavitary brachytherapy, the use of magnetic resonance imaging‐based image‐guided adaptive brachytherapy is becoming increasingly widespread because it allows dose escalation to the tumor and accurately evaluates the dose delivered to the surrounding normal organs. According to current evidence, a minimal dose of D90% of the high‐risk clinical target volume is significantly relevant to local control. Further improvements in target coverage have been achieved with combined interstitial and intracavity brachytherapy for massive tumors with extensive parametrical involvement. Introducing artificial intelligence will enable faster and more accurate generation of brachytherapy plans. Charged‐particle therapies have biological and dosimetric advantages, and current evidence has proven their effectiveness and safety in cervical cancer treatment. Recently, radiotherapy‐related technologies have advanced dramatically. This review provides an overview of technological innovations and future perspectives in radiotherapy for cervical cancer.

Impact of human papillomavirus types on uterine cervical neoplasia

AbstractHuman papillomavirus (HPV) is a major cause of cervical cancer. As the natural history of HPV‐associated cervical lesions is HPV genotype‐dependent, it is important to understand the characteristics of these genotypes and to manage them accordingly. Among high‐risk HPVs, HPV16 and 18 are particularly aggressive, together accounting for 70% of HPV genotypes detected in cervical cancer. Other than HPV16 and 18, HPV31, 33, 35, 45, 52, and 58 are also at a high risk of progression to cervical intraepithelial neoplasia (CIN)3 or higher. Recent studies have shown that the natural history of HPV16, 18, 52, and 58, which are frequently detected in Japan, depends on the HPV genotype. For example, HPV16 tends to progress in a stepwise fashion from CIN1 to CIN3, while HPV52 and 58 are more likely to persist in the CIN1 to CIN2 state. Among the high‐risk HPVs, HPV18 has some peculiar characteristics different from those of other high‐risk HPV types; the detection rate in precancerous lesions is much lower than those of other high‐risk HPVs, and it is frequently detected in highly malignant adenocarcinoma and small cell carcinoma. Recent findings demonstrate that HPV18 may be characterized by latent infection and carcinogenesis in stem cell‐like cells. In this context, this review outlines the natural history of HPV‐infected cervical lesions and the characteristics of each HPV genotype.

The AOFOG recommendations on human papillomavirus vaccination in the Asia‐Pacific region

AbstractCervical cancer remains a disease burden in Asia. The Asia and Oceania Federation of Obstetrics and Gynecology envisages a need to produce a set of recommendations on the implementation of human papilloma virus vaccination program for both lower‐middle‐income countries (LMICs) and high‐income countries (HICs), with an attempt to harmonize the practices yet allow flexibility to cater for different cultures, religions, needs and background of individual countries/cities. International guidelines and literature were sought, and recommendations were made in seven selected areas, including (i) the target groups for vaccination, (ii) the doses of vaccination including the use of single‐dose vaccination, (iii) the types of vaccines, (iv) suggestions for special populations including those with previous HPV infection, human immunodeficiency virus carriers, and lesbian, gay, bisexual, transgender, questioning/queer group, (v) inter‐changeability and the need of revaccination/booster, (vi) novel technologies and vaccines, and (vii) public education.

Prospective comparative trial comparing O‐RADS, IOTA ADNEX model, and RMI score for preoperative evaluation of adnexal masses for prediction of ovarian cancer

AbstractIntroductionPreoperative assessment of ovarian tumors to distinguish between benign and malignant is important. At this time, many diagnostic models were available and the popularity of the risk of malignancy index (RMI) in Thailand is still high. The IOTA Assessment of Different NEoplasias in adneXa (ADNEX) model and the Ovarian‐Adnexal Reporting and Data System (O‐RADS) model were both new models with good performance.ObjectivesThe purpose of this study was to compare O‐RADS, RMI, and ADNEX models.DesignThis diagnostic study was performed using data from the prospective study.MethodsData from 357 patients from a previous study were included and calculated using the RMI‐2 formula then applied to the O‐RADS system and the IOTA ADNEX model. The diagnostic significance of the results was evaluated by receiver operating characteristic (ROC) analysis and pairwise comparison between models was made.ResultsThe area under the receiver operating characteristic curve (AUC) to distinguish an adnexal mass as a benign or malignant tumor was 0.975 (95% CI, 0.953–0.988) for the IOTA ADNEX model; 0.974 (95% CI, 0.960–0.988) for O‐RADS; 0.909 for RMI‐2 (95% CI, 0.865–0.952). There were no differences in pairwise AUC comparisons between the IOTA ADNEX and O‐RADS models, and both were better than those of RMI‐2.ConclusionsThe IOTA ADEX and O‐RADS models are excellent tools for distinguishing the adnexal mass in the preoperative assessment and were better than RMI‐2. The use of one of these models is recommended.

Spatial distribution of tumor‐resident macrophages as predictive biomarkers in endometrial cancer

Abstract Background To investigate the role of CD47 expression and its relationship with tumor‐resident macrophages, specifically at the tumor margin, in patients with type II endometrial cancer. This study aims to elucidate whether CD47 could serve as a prognostic marker and to understand the dynamics between CD47 and macrophages, which could inform new therapeutic strategies. Methods A retrospective cohort study was conducted involving 75 patients of type II endometrial. Immunohistochemical analysis was performed to assess CD47 expression and macrophage markers (CD68 and CD163). Results The study found no direct correlation between CD47 expression levels and overall survival ( p  = 0.32), challenging its role as an independent prognostic marker in type II endometrial cancer. The higher expression of CD47 had significantly less incidence of endometrioid carcinoma G3 ( p  = 0.047). The negative correlation between CD47 H‐score and the density of CD68‐positive macrophages at tumor margin was statistically significant ( p  = 0.049). A high density of CD68‐positive macrophages at the tumor margin but a low density of CD163‐positive macrophages at the tumor margin were associated with poorer prognosis ( p  = 0.036). Conclusions The complex interaction between CD47 and macrophages, particularly at the tumor margin, suggests new avenues for targeted therapy in type II endometrial cancer.

Quality of care measurement for patients with ovarian cancer in Japan

Abstract Aim Quality of care is important to reduce disease progression, and improve both survival and quality of life. The Japan Society of Gynecologic Oncology has published treatment guidelines to promote standardized high‐quality care for ovarian cancer in Japan. We developed quality indicators based on the guideline recommendations and used them on large datasets of health service use to examine the quality of ovarian cancer care. Methods A panel of experts developed the indicators using a modified Delphi method. Adherence to each indicator was evaluated using data from a hospital‐based cancer registry of patients diagnosed in 2018. All patients receiving first‐line treatment at participating facilities were included. The adherence rates were returned to participating hospitals, and reasons for nonadherence were collected. A total of 580 hospitals participated, and the study examined the care received by 6611 patients with ovarian cancer and 1879 with borderline tumors using 11 measurable quality indicators. Results The adherence rate ranged from 22.6% for “Estrogen replacement within 6 months of operation” to 93.5% for “Bleomycin, etoposide, and cisplatin for germ cell tumor more than Stage II.” Of 580 hospitals, 184 submitted the reasons for nonadherence. Conclusions The quality of ovarian cancer care should be continuously assessed to encourage the use of best practices. These indicators may be a useful tool for this purpose.

Niraparib as a therapeutic agent for the treatment of ovarian cancer meningeal dissemination with BRCA1 mutation

AbstractThis study analyzed a 63‐year‐old woman with hereditary BRCA1 mutation. She underwent interval debulking surgery after neoadjuvant chemotherapy for high‐grade serous ovarian carcinoma (HGSOC). After 2 years of postoperative chemotherapy, she developed headache and dizziness, and a suspected metastatic cerebellar mass in left ovary was detected. Pathological analysis of the mass revealed HGSOC, which was removed surgically. Eight months and another 6 months after the surgery, local recurrence was noted; hence, she underwent CyberKnife treatment. After 3 months, cervical spinal cord metastasis was found, evidenced by left shoulder pain. Moreover, meningeal dissemination was present around the cauda equina. Chemotherapy treatment, including bevacizumab, was ineffective and increased lesions were observed. After CyberKnife treatment for the cervical spinal cord metastasis, niraparib was initiated for the meningeal dissemination. The cerebellar lesions and meningeal dissemination improved within 8 months of niraparib treatment. Although meningeal dissemination is challenging to treat, niraparib may be useful in BRCA‐mutated HGSOC.

Analysis of risk factors for patients with early‐stage cervical cancer: A study of 374 patients

AbstractAimThis study aimed to identify the postoperative histological features affecting the prognosis of patients with early‐stage cervical cancer who underwent open radical hysterectomy.MethodsThis retrospective study enrolled 374 patients with pT1a, 1b1 and 2a1 early‐stage cervical cancer who underwent open radical hysterectomy between 2001 and 2018. Survival outcomes were analyzed by Kaplan–Meier method and compared with log‐rank test. Using the Cox proportional hazards regression test, we conducted a multivariate analysis for disease‐free survival and overall survival.ResultsOthers histology, including other epithelial tumors and neuroendocrine tumors, had a significantly worse prognosis in both disease‐free survival and overall survival than those of squamous cell carcinoma and adenocarcinoma (hazard ratio, 4.37 and 11.76; P = 0.006 and P = 0.002, respectively), along with lymph node metastasis (hazard ratio, 2.99 and 7.03; P = 0.009 and P = 0.001, respectively).ConclusionOthers histology including adenosquamous carcinoma had a poor prognosis in early‐stage cervical cancer as with high‐risk factors.

Hyperammonemic encephalopathy associated with post‐radiotherapy vesicointestinal fistula following cervical cancer

AbstractThe majority of hyperammonemic encephalopathy is due to liver cirrhosis. However, urinary tract infection caused by urease‐producing bacteria increases ammonia in urine and can lead to hyperammonemic encephalopathy, especially in cases with obstructive uropathy and vesicointestinal fistula. This is the first case report of hyperammonemic encephalopathy in a cervical cancer patient associated with postradiotherapy vesicointestinal fistula. A 52‐year‐old woman developed diarrhea due to vesicosigmoidal fistula 14 years after radical hysterectomy and radiotherapy to treat cervical cancer. She refused urinary and/or fecal diversion. Twelve months after the diagnosis of fistula, she was admitted due to somnolence. Blood examination showed hyperammonemia without liver dysfunction. Urine culture showed Proteus rettgeri and Klebsiella pneumoniae. She recovered after intravenous antibiotics. Eight months after recovery, she was readmitted due to somnolence reoccurring with failed intravenous, but successful oral antibiotic treatment. She finally agreed to undergo percutaneous nephrostomy and hyperammonemia never recurred during 7 years of follow‐up.

Prognostic Significance of Actinin‐4 Protein Expression and Gene Amplification in Endometrial Carcinoma

ABSTRACT Objective This study aimed to investigate the clinical significance of actinin‐4 in endometrial carcinoma. Actinin‐4, an actin‐binding protein involved in cytoskeletal dynamics, has been implicated in the progression of various cancers; however, its precise role in endometrial carcinoma is not fully understood. This research sought to evaluate actinin‐4 protein expression and gene amplification and correlate these findings with clinicopathological parameters and patient survival to determine its prognostic value. Methods A retrospective analysis was conducted on endometrial carcinoma patients who underwent surgical resection. Actinin‐4 protein expression was assessed using immunohistochemical staining (IHC), and ACTN4 gene amplification was evaluated by fluorescence in situ hybridization (FISH). The intensity of actinin‐4 staining was graded, and gene amplification of ACTN4 was defined using the ACTN4 / CEP19 ratio. Statistical analysis, including Kaplan–Meier survival analysis and Cox proportional hazards modeling, was performed to correlate actinin‐4 expression with clinicopathological features and survival outcomes. Results Overexpression of actinin‐4 protein by IHC was significantly associated with advanced clinical stage and histological subtypes. While no significant difference was observed in overall survival (OS), patients with high actinin‐4 IHC demonstrated significantly poorer progression‐free survival (PFS). ACTN4 gene amplification by FISH was significantly associated with poorer prognosis for both OS and PFS compared to the group without amplification. Conclusion This study suggests that actinin‐4 plays a role in the progression of endometrial carcinoma, particularly influencing tumor aggressiveness and progression‐free survival.

A Survey of Current Practice and Perspectives on Lymphadenectomy in Minimally Invasive Surgery for Endometrial Cancer in Japan

ABSTRACT Objective This study investigated the reasons behind the decreasing trend of lymph node dissection for endometrial cancer (EC) in Japan, focusing on the impact of minimally invasive surgery (MIS) adoption, evolving clinical guidelines, and physician work‐style reform. Methods A cross‐sectional survey of the Japan Society of Gynecologic Oncology and Endoscopy (JSGOE) members was conducted to investigate facility demographics, MIS adoption, lymphadenectomy practices, factors influencing omission, impact of work‐style reform, and perspectives on future EC management, such as molecular classification and sentinel lymph node biopsy (SLNB). Results In total, 424 responses were received, representing a response rate of 67.8%. MIS adoption for EC is widespread in Japan, with laparoscopy preferred over robotic surgery. Lymphadenectomy is commonly performed; however, the criteria for omission varied among institutions, with clinical guidelines published by the Japanese Society of Gynecologic Oncology having the greatest impact. Physician work‐style reform significantly affected surgical practices such as surgical scheduling, adherence to time limits, and the number of surgeons participating in surgeries, while it had little impact on the criteria for lymphadenectomy omission. The adoption of molecular classifications is increasing with approximately half of the institutions planning to implement or having partially implemented them, while SLNBs remained relatively low. Conclusion This study highlights the significant impact of evolving clinical guidelines on lymphadenectomy practices for MIS for EC in Japan, and the limited impact of physician work‐style reform.

Long Term Disease Control of Brain Metastases From Chemotherapy‐Resistant Endometrial Cancer With Lenvatinib and Pembrolizumab: A Case Report

ABSTRACT Brain metastases from endometrial carcinoma are extremely rare and associated with poor prognosis. We present a 43‐year‐old woman with mismatch repair deficient endometrial cancer who developed multiple brain metastases refractory to cytotoxic chemotherapy and without extracranial involvement. After stereotactic radiotherapy, combination therapy with lenvatinib and pembrolizumab resulted in sustained partial remission for 16 months, with no evidence of brain hemorrhage. This case demonstrates that lenvatinib plus pembrolizumab may offer an effective and safe therapeutic option for brain metastases from endometrial cancer, even in patients resistant to conventional therapy. Remarkably, this outcome challenges the traditionally poor prognosis of such cases and underscores the potential for novel targeted and immunotherapeutic strategies to redefine the standard of care for this rare and devastating complication.

The role of the microbiome in endometrial carcinoma: Pathogenesis, biomarkers, and therapeutic prospects

Abstract Aim Recent studies show that human microbiomes play a significant role in the development of endometrial carcinoma, which is a common gynecological cancer affecting women of reproductive age. This review provides an extensive analysis of how the microbiome interacts with endometrial carcinoma while focusing on its impact on disease progression and potential therapeutic advancements. Methods Extensive literature research was conducted to examine how microbial dysbiosis affects endometrial cancer development. The research analyzed both animal model studies and clinical cohort data to assess how microbiome composition influences cancer risk and progression alongside treatment outcomes. The research explored possible microbiome interventions alongside the translational challenges they present. Results New research findings demonstrate that microbial imbalance contributes to endometrial cancer development through chronic inflammatory processes and estrogen metabolism changes while affecting immune system behavior in the tumor microenvironment. Scientists are exploring unique microbial patterns to serve as biomarkers for detecting diseases and predicting treatment outcomes. Microbiome‐targeted strategies, including probiotics and diet changes, demonstrate the potential to enhance treatment results for individuals receiving immunotherapy and chemotherapy. Conclusions This review examines the detailed interactions between the microbiome and endometrial carcinoma and outlines their importance in developing predictive models and innovative treatments. We explore both the obstacles faced in applying microbiome research to clinical settings and potential research paths that could speed up the integration of microbiome‐based therapies into patient healthcare.

Successful treatment of chylous leakage with delayed presentation after endometrial cancer surgery using dietary therapy, octreotide, and computed tomography‐guided lymphangiography: A case report and literature review

Abstract Objective Chylous ascites (CA) is a rare yet clinically significant complication following gynecologic cancer surgery, with incidence rates of 0.17 % to 9%. We aimed to describe a case of CA with a delayed clinical presentation nearly 100 days postoperatively in a patient with advanced endometrial cancer and to review the management strategies. Methods We retrospectively evaluated a 75‐year‐old patient who underwent radical hysterectomy, bilateral salpingo‐oophorectomy, extended lymphadenectomy (pelvic and para‐aortic), and partial omentectomy for stage IIIB endometrial cancer. Data collected included onset timing, ascitic fluid analysis, imaging findings, and treatment responses. Additionally, a narrative review identified 13 relevant studies discussing the onset, risk factors, diagnosis, and therapies for post‐operative CA in gynecologic oncology. Results Although CA typically appears within 4 to 21 days, our patient developed CA at approximately post‐operative day 99. Diagnostic paracentesis confirmed triglyceride‐rich ascitic fluid, establishing the diagnosis of CA. Dietary modification (fasting followed by medium‐chain triglyceride diet), octreotide therapy, and computed tomography (CT)‐guided lymphangiography effectively controlled the chylous leakage without requiring surgery. Conservative measures—low‐fat or medium‐chain triglyceride diets, total parenteral nutrition, and somatostatin analogs—are considered first‐line, while lymphangiography/embolization and eventual surgical ligation may be needed for refractory cases. Conclusions This case illustrates that CA with a delayed clinical presentation can be successfully treated with a stepwise conservative approach comprising dietary therapy, octreotide, and CT‐guided lymphangiography, even when presenting more than 3 months postoperatively. Moreover, our patient remained free of disease recurrence at 1 year and 8 months postoperatively, underscoring that timely management of CA can avoid delays in adjuvant therapy.

High‐grade vaginal intraepithelial neoplasia after hysterectomy for high‐grade cervical intraepithelial neoplasia: Is hysterectomy a “definitive” treatment compared to conization?

AbstractAimWe investigated the frequency of early recurrence of vaginal intraepithelial neoplasia grade 2/3 (VaIN 2/3) (within 2 years) after hysterectomy for cervical intraepithelial neoplasia grade 3 (CIN3). The characteristics of the clinicopathological factors common to them were explored including different surgical methods.MethodsAs a retrospective observational study, a total of 647 CIN3 patients were divided into a conization and hysterectomy group (C group, n = 492; H group, n = 155), and HSIL (CIN2/3 or VaIN2/3) recurrence within 2 years after surgery was evaluated. A stratified analyses was performed. Surgical methods were divided into trans‐abdominal, trans‐vaginal, and laparoscopic.ResultsThe recurrence of VaIN3 was detected in four cases (2.6%) in the H group, which was similar to that of CIN2/3 in the C group, 12 out of 491 patients (2.4%). The patients who developed VaIN3 were significantly older than those who did not (median, VaIN3: 71.0; VaIN1 and less: 48.0; p < 0.0001). All VaIN3 cases were detected within 5 months, although majority of cases were negative in the margin (3/4 cases; margin negative). The method of hysterectomy was not related to the VaIN3 recurrence.ConclusionFor CIN3 patients for whom hysterectomy is the main treatment, VaIN3 can develop in 2.6% within very shortly after operation even if surgical margin was negative. The elder the age, the higher the risk of early recurrence could be. Laparoscopic surgery is considered to be acceptable methods of hysterectomy.

Raynaud's phenomenon as a presenting manifestation of ovarian cancer: A case report

AbstractRaynaud's phenomenon (RP) is characterized by episodes of vasospasm affecting the hands and feet. Paraneoplastic RP, as a single presenting symptom is rarely seen in cases of ovarian cancer (OC), and thus may lead to misdiagnosis. We present a case of paraneoplastic RP in a patient with high‐grade serous OC. A 66‐year‐old female presented with dyspnea and bilateral peripheral cyanosis involving her fingers. CA125 was elevated (423 U/mL). CT revealed a pleural effusion on the left side, suspicious omental lesions and ascites. Omental biopsy and pleural cytology demonstrated high‐grade serous OC. Neoadjuvant chemotherapy (carboplatin/paclitaxel) resulted in objective improvement in finger ischemia and complete regression of vasospastic features. However, the patient's disease was refractory to post‐surgical treatment and eventually she deceased of multiple organ failure. To conclude, RP may be a presenting symptom of OC. It is important to determine the underlying disease and develop an effective treatment strategy.

Endometrial cancer and simultaneous pregnancy, an unusual combination. Case report

AbstractUterine cancer is the fourth most common cancer in women. Declining fertility, combined with increasing overweight and diabetes, might be some of the causes accountable for the rapid increase in the incidence of endometrial cancer (EC). Around 5% of EC are diagnosed in women aged under 40 years. We present a case of EC in a 36‐year‐old woman confirmed by hysteroscopy‐directed biopsy, who became pregnant before receiving any primary treatment. She had no other significant medical or family history of interest. Image staging found a uterine‐confined disease. The pregnancy had a normal course. The patient refused any type of treatment after delivery; thus, she was closely monitored every 3 months. No signs of disease recurrence were detected during the follow‐up. Pregnancy may be possible with early EC and it might an effective treatment for the disease in this case. The pregnancy acts as treatment and the gestation could continue until term without complications, in this patient diagnosed with EC.

A potential inflammatory biomarker for advanced endometrial cancer treated with lenvatinib plus pembrolizumab

AbstractIntroductionTo identify prognostic biomarkers that could predict how well patients will respond to lenvatinib/pembrolizumab (LEN/PEM). The utility of certain inflammatory biomarkers in endometrial liquid‐based cytology (LBC) or peripheral blood samples, such as neutrophil counts, lymphocyte counts, and neutrophil‐to‐lymphocyte ratio (NLR) were explored.MethodsThe study included 25 patients with advanced or recurrent endometrial cancer who had received LEN/PEM between August 2018 and March 2024. Predictors for overall response (OR), disease control, and progression‐free survival, based on neutrophil/lymphocyte counts, NLR scores of the endometrial LBC prior to initial treatment, and peripheral blood prior to initial treatment and prior to LEM/PEM treatment were compared using a receiver operating characteristic curve. Significant predictors were evaluated using the log‐rank test, and multivariate analysis.ResultsAlthough neutrophil counts and NLR score in endometrial LBC prior to initial treatment were better effective predictors for OR, the most accurate predictor of a progression‐free status was NLR score in peripheral blood prior to LEM/PEM (0.722, 95% CI: 0.45–0.99, sensitivity: 57.1%, specificity: 94.4%). In peripheral blood prior to LEN/PEM, the lower NLR (NLR <5.39) group had a significantly longer PFS than the higher NLR (5.39 ≤ NLR) group (p = 0.023, median survival: 13.5 vs. 3.0 months), and tended to be independently correlated with PFS (hazard ratio = 2.571; 95% CI = 0.857–7.719; p = 0.092).ConclusionInflammatory biomarkers in endometrial LBC failed to predict the efficacy of LEN/PEM, while peripheral blood NLR score sampled prior to LEN/PEM potentially could be a significant predictor.

Questionnaire survey regarding current status of minimally invasive surgery for endometrial cancer in Japan: A cross‐sectional survey for JSGOE members

AbstractAimMinimally invasive surgery (MIS) has been introduced as an alternative to more radical surgical procedures. The Japan Society of Gynecologic and Obstetric Endoscopy and Minimally Invasive Therapy conducted a cross‐sectional questionnaire survey to ascertain the status of MIS for endometrial cancer.MethodsThe survey was conducted between May 10 and June 30, 2022. The questionnaire included information on personal attributes, academic affiliations, qualifications, hysterectomies, and intraoperative procedures performed.ResultsThe total number of questionnaire respondents was 436 (9.2% of the membership). The hysterectomy methods and percentage performed were as follows: simple total hysterectomy (equivalent to benign surgery), 3%; simple total hysterectomy with care to avoid shaving the cervix, 31%; extended total hysterectomy, 48%; and modified radical hysterectomy, 15%. An analysis of hysterectomies performed using MIS for endometrial cancer by qualified gynecologists of endoscopy or board‐certified gynecologic oncologists showed a tendency not to choose simple total hysterectomy compared to the gynecologists who did not hold certification (p = 0.019, p = 0.045, and p = 0.010, respectively). Additionally, 67% of respondents did not use uterine manipulators, and 59% of the respondents did not perform lymph node dissection following the guidelines for treating endometrial cancer in Japan.ConclusionThis study provided the current status of MIS for endometrial cancer in Japan. The hysterectomy method, use of uterine manipulators, and criteria for omitting lymph node dissection were generally in agreement with the guidelines. Currently, an extra‐fascial simple hysterectomy, including at least not shaving the cervix, was a major method for early invasive endometrial cancer using MIS.

Efficacy and toxicity of pegylated liposomal doxorubicin as therapy for recurrent ovarian cancer in relation to the number of previous chemotherapy regimens: Comparison with gemcitabine

AbstractAimPegylated liposomal doxorubicin (PLD) is one of the second‐line chemotherapy regimens for platinum‐resistant recurrent ovarian cancer, but in clinical practice, it is also used for third or subsequent lines of chemotherapy. There is no report on the efficacy and toxicity of PLD in relation to the number of previous chemotherapy regimens. The purpose of this study was to clarify these points and compare with the results of gemcitabine (GEM) therapy we reported previously.MethodsWe retrospectively reviewed the medical records of patients with platinum‐resistant recurrent ovarian cancer who underwent two or more cycles of PLD therapy between July 2009 and March 2017 at our institution. We used our reported data of GEM for comparison analysis.ResultsSeventy‐eight patients were enrolled in this study. The overall response rate was 19.2% and the disease control rate (DCR) was 53.8%. The DCR with 1, 2, 3, and 4 or more previous regimens was 53.8%, 48.6%, 63.6% and 66.7%, respectively. Grade 3/4 neutropenia and anemia developed in 59.0% and 12.8%, respectively. Grade 2 or higher hand ‐foot syndrome, stomatitis, and liver dysfunction developed in 25.6%, 25.6% and 2.6%, respectively. When the number of previous regimens was 3 or higher, the DCR of PLD was significantly higher than that of GEM (64.7% vs 30.8%, P = 0.037).ConclusionThe DCR did not decrease with a greater number of previous regimens. When the number of previous regimens was 3 or higher, PLD therapy had a superior DCR to GEM therapy. Toxicity was tolerable in PLD therapy.

Management of recurrent granulosa cell tumor of the ovary: Contemporary literature review and a proposal of hyperthermic intraperitoneal chemotherapy as novel therapeutic option

AbstractGranulosa cell tumors of the ovary (GCT) are the most common type of sex cord stromal tumors. Although most of patients are diagnosed at early stage and has favorable 5‐year overall survival rate, 16–23% of GCT ultimately develop recurrent disease. Recurrences are characterized by disseminated peritoneal metastasis. The treatment options include systemic chemotherapy, secondary CRS or palliative localized radiation therapy have not yet standardized due to the rarity of disease. Aggressive CRS followed up by hyperthermic intraperitoneal chemotherapy (HIPEC) has been shown to provide benefit in other peritoneal disease but limited data available for recurrent GCT. We have a case of recurrent Adult‐type GCT (AGCT) who was treated with CRS followed by HIPEC with mitomycin C and doxorubicin. The patient has no evidence of recurrence for approximately 11 years. An electronic search of the PubMed database with the following search terms: GCT, HIPEC showed that there were total 21 patients with recurrent GCT treated in seven different studies and 13 of 21 (61.9%) patients had no evidence of disease during follow‐up ranging from 6 to 100 months. Three patients (14.2%) died of the disease. Six studies used cisplatin for HIPEC. At least 76.2% (16 of 21, data not available for five patients) had complete cytoreduction with total 16 cases of perioperative complications but no perioperative mortality was observed. Although further investigation is needed, we propose that CRS and HIPEC can be an effective therapeutic option for recurrent GCT at experienced institutions.

Hyperthermic intraperitoneal chemotherapy (HIPEC) for gynecological cancer

AbstractAimHyperthermic intraperitoneal chemotherapy (HIPEC) is a method of administering anticancer agents directly while heating the abdominal cavity. The aim of this review is to know the current position of HIPEC in ovarian cancer and uterine sarcoma and its future prospects.MethodsThis article reviews the current literature and evidence for the clinical trial of HIPEC in ovarian cancer and uterine sarcoma with consideration of the cases treated in our department.ResultsIn January 2018, van Driel et al. reported the results of their phase 3, randomized, controlled trial and the usefulness of neoadjuvant chemotherapy followed by interval debulking surgery. With respect to greater than grade 3 complications, such as suture failure, intestinal perforation, postoperative bleeding, wound issues and death, there were no significant differences between the HIPEC group and the no‐HIPEC group. In a meta‐analysis including two randomized, controlled studies and 11 observational studies in 2019, the addition of HIPEC to cytoreductive surgery significantly improved overall survival of ovarian cancer patients. Moreover, growing evidence of the efficacy of cytoreductive surgery with HIPEC has also been reported in uterine sarcoma with peritoneal sarcomatosis in a multi‐institutional study. HIPEC could be one of the new therapeutic strategies for such disseminated peritoneal lesions.ConclusionSince the usage regimen and temperature setting of HIPEC are not standardized, and its effectiveness and adverse events are greatly affected by the time of administration, it is necessary to consider clinical trials for the optimization and establishment of HIPEC in Japan in the future.

Mechanisms to increase cascade testing in hereditary breast and ovarian cancer: Impact of introducing standardized communication aids into genetic counseling

AbstractAimPrecancer identification of women with hereditary breast and ovarian cancer (HBOC) could prevent 20% of these ovarian cancers. The objective was to determine whether standardized Facing Our Risk of Cancer Empowered (FORCE) materials are acceptable, improve knowledge of HBOC and increase disclosure to family members.MethodsA prospective cohort of women with breast or ovarian cancer was identified prior to genetic testing. Subjects completed a baseline knowledge survey and were provided three communication aids. Knowledge, acceptability and communication to family members were reassessed at 6 months and compared to a retrospective cohort who had undergone genetic testing for breast or ovarian cancer prior to the intervention. The primary outcome was increase in HBOC knowledge, requiring 20 pre‐ and postknowledge scores to detect a 10% difference.ResultsForty women were enrolled. The median age at cancer diagnosis was 50 years and 55% had a family history of breast or ovarian cancer. Though subjects found the resources acceptable, knowledge scores did not improve after their use. Disclosure rates were of no different between cohorts (83% preintervention vs 77% postintervention, P = 0.26) though there was an increase in deleterious mutation carriers, 0% (0/6) preintervention vs 100% (22/22) postintervention. Rates of subsequent testing in relatives were low in both preintervention and postintervention cohorts (0% vs 4.5%).ConclusionInclusion of standardized communication tools is acceptable to patients. Knowledge did not improve after their use. In deleterious mutation carriers, disclosure rates increased postintervention.

Fertility‐sparing treatment for early‐stage epithelial ovarian cancer: Contemporary oncologic, reproductive and endocrinologic perspectives

AbstractAimEpithelial ovarian cancer (EOC) can be a devastating diagnosis in women of reproductive age who desire future fertility. However, in early‐stage disease, fertility‐sparing surgery (FSS) can be considered in appropriately selected patients.MethodsThis is a narrative descriptive review of the recent literature on FSS for EOC from oncologic, reproductive and endocrinologic perspectives.ResultsThe recurrence rate following FSS performed for stage I EOC in published retrospective studies collectively is 13% but ranges from 5 to 29%, while mortality ranges from 0 to 18%. Five‐year disease‐free survival following FSS is over 90% but decreases with higher stage and grade. Recurrences following FSS are more likely to be localized with a more favorable prognosis compared to recurrences following radical surgery. Adjuvant chemotherapy is recommended in women with high‐risk disease, and strategies to minimize gonadotoxicity during chemotherapy such as gonadotropin‐releasing hormone (GnRH) agonists may be considered. Oocyte, embryo and/or ovarian cryopreservation can also be offered to patients desiring future biologic children. Reproductive outcomes following FSS, including pregnancy and miscarriage rates, resemble those of the general population, with a chance of successful pregnancy of nearly 80%.ConclusionIn retrospective data, FSS appears to be oncologically safe in stage IA and IC grade 1–2 non‐clear cell EOC. In patients with grade 3 tumors or clear cell histology, treatment can be individualized, weighing a slightly higher risk of recurrence with fertility goals. A multidisciplinary approach with oncology and reproductive endocrinology may be of utility to help these patients achieve their fertility goals.

Case of ovarian steroid cell tumor diagnosed after presenting acute heart failure

AbstractWe report a rare case of an ovarian steroid cell tumor with a diagnosis prompted by heart failure symptoms. A 28‐year‐old Japanese nulligravida/nullipara with a chief complaint of respiratory discomfort during physical exertion and exhibiting heart failure symptoms was referred to our hospital. She also had signs of virilization, including secondary menorrhea since the age of 20, hirsutism and balding. Cushing's syndrome was suspected, and further examinations showed hypertestosteronemia and right ovarian tumor. Symptomatic treatment for heart failure with diuretics and antihypertensives was followed by abdominal right adnexectomy performed due to the androgen‐producing ovarian tumor. The tumor was solid and larger than a fist, and confirmed as a steroid cell tumor through postoperative histopathology. Serum total testosterone levels normalized at day 3 postoperatively, and menstruation resumed 2 months later. Our case was diagnosed due to heart failure symptoms, and its treatment resulted in improvement in virilization signs.

Manual vacuum aspiration (women's MVA) for endometrial biopsy for patients with suspected endometrial malignancies

AbstractAimEndometrial biopsy is generally performed with a metal uterine curette sonde; however, recently, many types of vacuum aspirators are available, including the manual vacuum aspiration (MVA) system. We used the women's MVA system for endometrial sampling and evaluated its effectiveness in determining the presence of endometrial malignancy.MethodsForty‐seven samples were examined using the following procedures after measuring endometrial thickness by transvaginal ultrasonography: fractional curettage biopsy (Bx; 20 samples), total curettage under general anesthesia (T/C; 13 samples), and MVA (14 samples). The quality of the endometrial samples was classified into four types: 1–4, where 1 denoted poor and 4, good quality.ResultsThe mean score of the MVA group was significantly higher than that of the partial curettage biopsy group (p = 0.0065). No differences were observed between the MVA and total curettage groups (p = 1.00). When patients were divided into two groups according to endometrial thickness (<10 mm or ≥10 mm) and analyzed, both the MVA and T/C groups did not show a significant difference in their scores compared to the Bx group when the endometrial thickness was <10 mm. However, when the endometrial thickness was ≥10 mm, the MVA and T/C groups had significantly better scores than the Bx group (p = 0.0225 and p = 0.0244, respectively). Vagal reflex, as an adverse event, was observed only in two patients in the Bx group (2/20, 10%).ConclusionConsidering its quality and safety, Karman‐type MVA for endometrial sampling could be an alternative to fractional curettage using a metallic uterine curette sonde.

Clinical characteristic and prognostic factors in high‐grade endometrial neuroendocrine carcinoma

AbstractAimThe aim of the present study was to summarize the clinical characteristics and analyze the independent prognostic factors in patients with high‐grade endometrial neuroendocrine carcinoma (ENC).MethodsPatients diagnosed with ENC, endometrioid adenocarcinoma (EAC), endometrial clear‐cell carcinoma (ECC), endometrial serous carcinoma (ESC), endometrioid carcinoma with mucinous features (EMC) from 1987 to 2016 were screened from the National Cancer Institute database (surveillance, epidemiology, and end results [SEER]). Kaplan–Meier were used to assess survival. Univariate and multivariate Cox proportional hazards analysis were done to examine factors affecting survival.ResultsThe median survival times of ENC were 11 months, shorter than that of EAC, ECC, ESC, and EMC (p < 0.01). There was no significant difference in ages, survival rate, and median survival time between large‐cell ENC (LCENC) and small‐cell ENC (SCENC), which were all belong to ENC. In a multivariable model, the hazard ratio (HR) of death for women with Federation International of Gynecology and Obstetrics (FIGO) stage I‐II of ENC was 0.37 compared to FIGO stage III‐IV (p < 0.01). The HR of patients who under the surgery was 0.39 compared to the patients who without surgery (p < 0.01), and the HR of patients who received chemotherapy was 0.51 compared to the patients who did not received chemotherapy (p < 0.01). Radiotherapy did not significantly reduce the mortality risk of patients.ConclusionENC was a kind of devastating endometrial cancers with the poorest prognosis. Surgical treatment and chemotherapy were necessary for improving prognosis of ENC. Early diagnosis favored better prognosis. There was no prognostic difference between with and without radiotherapy.

Huge broad ligament leiomyoma with cystic degeneration: A diagnostic and surgical challenge

AbstractBroad ligament is the common extrauterine site for fibroid. We present a case of huge broad ligament fibroid with cystic degeneration. Patient presented with abdominal swelling and mild pain abdomen. On abdominal examination, a large tense cystic mass of 34 weeks gravid uterus size arising from pelvis was noted. Cervix was pulled up and all fornices were full with mass on pelvic examination. Ultrasound suggested adnexal mass as ovaries were not seen. Contrast‐enhanced computed tomography abdomen too reported adnexal mass likely of ovarian origin. On laparotomy, 6 L of straw color fluid drained from the mass which was seen arising from left broad ligament, bilateral ovaries were separate from the mass and appeared healthy. Enucleation of mass was done to ease the hysterectomy and careful evaluation of ureteric course was done throughout the surgery to avoid its injury. Total hysterectomy with bilateral salpingo‐opherectomy and pelvic lymphadenectomy was performed. This case is being reported for its rare incidence, diagnostic dilemma and surgical challenge.

Therapeutic potential of combination therapy of soluble VEGF receptor 1 and conventional chemotherapy for ovarian cancer growth

AbstractAimThis study aimed at evaluating the additional anti‐tumor effects of exogenous rVEGFR1 (sFlt1) on conventional chemotherapy in ovarian cancer cell lines.MethodsWe utilized cells from two ovarian cancer cell lines, SKOV3 and HeyA8, and treated them with a combination of rVEGFR1 (sFlt1) and carboplatin as well as rVEGFR1 (sFlt1) alone. First, we evaluated cell survival after treatment by using cell counting and MTS assays. Next, we performed Ki67 staining for evaluating the inhibitory effects of the treatment on cell proliferation, and a lactate dehydrogenase (LDH) assay for evaluating cytotoxicity. Finally, to determine whether MAP kinase signaling is involved in this process, we performed western blot analysis of extracellular signal‐regulated kinase (ERK), phospho‐ERK, c‐jun n‐terminal kinase (JNK) and phospho‐JNK.ResultsThe cytotoxic and growth‐restriction effects were more pronounced in the group co‐administered with rVEGFR1 (sFlt1) and carboplatin than in cells treated with either rVEGFR1 (sFlt1) or carboplatin alone. Quantitative analysis of Ki67‐positive cells also showed a decreased proportion of Ki67‐positive cells in SKOV3 cells treated with a combination of exogeneous rVEGFR1 (sFlt1) and carboplatin compared to that in cells treated with either rVEGFR1 (sFlt1) or carboplatin alone. In the LDH assay, we also found significantly enhanced cell toxicity from the combination therapy. Finally, western blotting analysis showed that the MAPK signaling pathway was not affected by sFlt1 treatment.ConclusionThis study confirmed the additive effects of rVEGFR1 (sFlt1) combined with conventional chemotherapy for ovarian cancer growth in in vitro assays, thus suggesting the combination of rVEGFR1 (sFlt1) and carboplatin as a potential novel therapeutic option for ovarian cancer.

Relationship between ascites volume and clinical outcomes in epithelial ovarian cancer

AbstractObjectiveAscites is a tumor microenvironment, ascites and massive ascites‐induce compression could promote the progression of epithelial ovarian cancer (EOC); however, the impact of ascites volume on clinical outcomes has not been studied extensively. We aimed to investigate the association between ascites volume and clinical outcomes especially platinum resistance in EOC.MethodsWe retrospectively evaluated a total of 546 EOC patients with respect to the amount of ascites, clinicopathologic factors, and survival. Using the threshold of 1500 ml to classify patients into small‐ and large‐volume ascites groups, we analyzed the correlation between ascites volume and clinicopathological factors, including platinum‐free interval (PFI), and prognosis.ResultsPatients with large volume ascites were more likely to present with later stage disease, primary platinum‐resistant (PPR) cancer, and suboptimal cytoreduction. Prolonged PFI was associated with decreased ascites volume. The large‐volume ascites group showed worse progression‐free survival (PFS) and overall survival (OS). An increase in ascites volume was associated with an increased risk of disease recurrence (hazard ratio [HR] = 1.115, 95% confidence interval [CI]: 1.035–1.200) and death (HR = 1.213, 95% CI: 1.090–1.350).ConclusionsAscites was an independent predictor of PFS and OS in EOC patients. A large volume of ascites predicated a shortened PFI, an increased incidence of PPR and suboptimal cytoreduction. Thus, the volume of ascites is a simply available clinical parameter, which could be used to evaluate the prognosis and platinum resistance of EOC patients early, it contributes to formulate individualized treatment plan and improve the outcome of EOC patients.

Quantitative analysis of ovarian cysts and tumors by using T2 star mapping

AbstractAimThe aim of this study was to investigate the efficacy of T2 star (T2*) mapping in diagnosing ovarian cysts/ tumors.MethodsPelvic magnetic resonance examinations including T2*WI were performed before surgery in 35 patients. The region of interest, consisted of a 10 mm2 diameter circle, was set as much as possible inside ovarian tumors/cysts to measure T2*values, and mean T2* values were compared in ovarian cyst/tumor types, retrospectively. Diagnoses of 40 ovarian cysts/tumors were determined by pathological reports, in which 17 were endometriomas, 13 were mature cystic teratomas, 6 were mucinous cystadenomas and 4 were serous cystadenomas.ResultsThe average T2* values of endometrioma was 56.8 ± 8.7 ms (mean ± SEM), which was significantly lower than that of mucinous cystadenoma (334.2 ± 58.5 ms, mean ± SEM) or serous cystadenoma (237.0 ± 45.4 ms, mean ± SEM). There was no difference in T2* values between endometrioma and mature cystic teratoma (64.1 ± 22.6 ms, mean ± SEM).Receiver operating characteristics curve analysis revealed that optimal cut‐off value for differential diagnosis of endometrioma and mucinous or serous cystadenoma was 149.2 ms as T2* value, which has an area under the curve of 0.95 (sensitivity = 92.4%, specificity = 78.6%).ConclusionT2* values were useful to diagnose various types of ovarian cyst/tumor.

Endometrioid adenocarcinoma arising from abdominal wall endometriosis: A case report and literature review

AbstractEndometriosis, affecting 6%–10% of women of reproductive age, can lead to severe symptoms such as chronic pelvic pain and infertility. Among its rarer manifestations is abdominal wall endometriosis (AWE), which has been increasingly reported following cesarean deliveries. This case discusses a 39‐year‐old woman who presented with a 13‐year history of cyclical pain at her cesarean section scar, exacerbated over the last year by the development of a painful abdominal mass. Medical evaluations indicated endometriosis at the scar, with further investigations including ultrasound and magnetic resonance imaging showing involvement of the rectus abdominis muscle. Elevated tumor markers HE4 and CA‐125, along with a biopsy, confirmed adenocarcinoma. The patient underwent extensive surgical treatment, including the resection of the mass, hysterectomy, bilateral salpingo‐oophorectomy, and lymphadenectomy. Pathology confirmed moderately differentiated infiltrative adenocarcinoma originating from endometriosis. Despite the absence of postoperative chemotherapy, the patient showed no recurrence, emphasizing the effectiveness of comprehensive surgical management. This case highlights the critical importance of recognizing the potential for malignant transformation in AWE, particularly following cesarean deliveries, and underscores the necessity for vigilant monitoring and personalized treatment strategies. The management of AWE, especially when malignant transformation is suspected, necessitates a multidisciplinary approach similar to that used in ovarian cancer, focusing on rigorous surgical intervention and the potential for adjuvant therapies.

Prognostic significance of Ki67 during neoadjuvant chemotherapy in primary unresectable ovarian cancer

AbstractAimThe purpose of this study was to investigate whether the Ki67 values were associated with survival for predicting prognosis in patients with advanced ovarian cancer receiving neoadjuvant chemotherapy (NACT).MethodsAmong 17 patients treated with NACT, 13 patients were available for tissue samples from matched pre‐ and post‐therapy tissues. Ki67 scores were transformed to a logarithmic scale for the statistical analyses. The optimal cutoff values of the log‐phase Ki67 were assessed by receiver operating characteristic (ROC) analysis. Kaplan–Meier analysis, the log‐rank test, and Cox regression analysis were carried out to analyze survival.ResultsThe Ki67‐decrease and post‐NACT Ki67 were the independent factors associated with relapse‐free survival (RFS) (p < 0.001 and p = 0.003). No association was observed on overall survival. The optimal cutoff values for the Ki67‐decrease and the post‐NACT Ki67 were 6.67% and 5.46 based on ROC where the area under ROC curves (AUC) were 1.00 (p < 0.001) with the 100% sensitivity and specificity. The median RFS was 537 days in patients showing Ki67‐decrease >6.66% or post‐NACT Ki67 level <5.46, while it was 224 days in those with Ki67 decrease ≤6.66% or post‐NACT Ki67 level ≥5.46 (p = 0.001).ConclusionsThe Ki67‐decrease and the lower post‐NACT Ki67 are independent factors associated with favorable RFS, indicating that they could be precise biomarker candidates for prognosis in NACT‐administered patients with advanced ovarian cancer.

Annual report of the Committee on Gynecologic Oncology, the Japan Society of Obstetrics and Gynecology: Annual patient report for 2017 and annual treatment report for 2012

AbstractAimTo provide information including the trend of gynecological malignancies in Japan, we hereby present the Annual Patient Report for 2017 and the Annual Treatment Report for 2012, on the outcomes of patients who started treatment in 2012.MethodsThe Japan Society of Obstetrics and Gynecology maintains an annual tumor registry, where information on gynecological malignancies from various participating institutions is gathered. The data of patients whose treatment with gynecologic malignancies was initiated in 2017 were analyzed retrospectively. Survival of the patients who started treatment with cervical, endometrial and ovarian cancer in 2012 was analyzed by using the Kaplan‐Meier, log‐rank and Wilcoxon tests.ResultsTreatment was initiated in 2017 for 7710 patients with cervical cancer; 11 120 with endometrial cancer; 7029 with ovarian, tubal and peritoneal cancer; 2164 with ovarian borderline tumors; and with the others (213 vulvar cancer, 139 vaginal cancer, 366 uterine sarcoma, 41 uterine adenosarcoma and 131 trophoblastic diseases). This clinicopathological information was summarized as the patient annual report. The 5‐year survival rates of the patients with cervical cancer were 92.9, 75.5, 58.2 and 26.7% for stages I, II, III and IV, respectively. The 5‐year survival rates for the patients with endometrial cancer were 93.6, 85.6, 72.6 and 27.3% for stages I, II, III and IV, respectively. The 5‐year survival rates for the patients with ovarian cancer (surface epithelial‐stromal tumors) were 92.5, 83.5, 49.5 and 30.8% for stages I, II, III and IV, respectively.ConclusionThe annual tumor report is an important survey that provides knowledge on gynecological malignancy trends in Japan.

Research progress in teratoma‐associated anti‐N‐methyl‐D‐aspartate receptor encephalitis: The gynecological perspective

AbstractAimAnti‐N‐methyl‐D‐aspartate receptor (NMDAR) encephalitis is one of the autoimmune encephalitis, which often occurs in children and young adults, especially in young women. In addition to viral infection, teratoma is an important causative factor. Anti‐NMDAR encephalitis is well known to neurologist. However, this is less well known to gynecologists, who may have a decisive role in etiological management. Therefore, from the perspective of gynecologists, we provide an overview of the relationship between the encephalitis and ovarian teratoma, the clinical features and treatment of this disease, and prognosis of pregnant women with this encephalitis.MethodsWe searched the PubMed database using the search terms in various combinations “teratoma,” “dermoid cyst,” “ovary,” “ovarian,” “anti‐NMDAR encephalitis,” and “N‐methyl‐D‐aspartate receptor.”ResultsAccording to the current literature, the mechanism of anti‐NMDAR encephalitis is probably due to the ectopic expression of the NMDAR in the teratomas tissue. The disease has a high mortality rate if not treated promptly and effectively. An important way to improve patients' outcome is to remove the ovarian tumor in time. Pregnant women are also at risk of developing anti‐NMDAR encephalitis during pregnancy. The fetal outcome is usually better in patients with mid‐ to late‐pregnancy onset than in early pregnancy, and patients are often able to maintain their pregnancies into late pregnancy.ConclusionYoung women with sudden onset of abnormal psychiatric behavior should be actively screened for ovarian tumors and, if confirmed to be teratoma‐associated anti‐NMDAR encephalitis, should undergo gynecologic surgery as early as possible, which can help improve their prognosis.

Global, regional, and national burden of ovarian cancer and the attributable risk factors in all 194 countries and territories during 2007–2017: A systematic analysis of the Global Burden of Disease Study 2017

AbstractBackgroundWe estimated the global burden of ovarian cancer (OC) in 194 countries and territories between 2007 and 2017.MethodsData were extracted from the Global Burden of Disease (GBD), Injuries, and Risk Factors 2017 study.ResultsGlobally, 286 126.80 (95% UI = 278 075.38–295 311.41) incident cases, 4.67 million (4.53–4.83) disability‐adjusted life‐years (DALYs), and 175 981.99 (171 384.15–181 198.43) deaths were reported in 2017. The age‐standardized incidence and DALY rates increased by 2.05% and 1.34% during 2007–2017, respectively, while the age‐standardized mortality rate decreased by −0.14%. The age‐standardized incidence, DALY, and mortality rates in 2017 were the highest in the high socio‐demographic index (SDI) quintile, but the largest percentage increase during 2007–2017 was in the low‐SDI quintile. Among regions, Central Europe showed the highest 2017 age‐standardized incidence, DALY, and mortality rates, whereas South Asia and East Asia showed the largest percentage increases in both rates during 2007–2017. Among countries, India showed the largest percentage increase in age‐standardized incidence and DALY rates, whereas Iran showed the largest percentage increase in age‐standardized mortality rates. Globally, the largest percentage increase in risk‐attributable DALYs was associated with metabolic risk factors (e.g., high fasting plasma glucose levels).ConclusionThe global age‐standardized incidence, DALYs, and mortality rates of OC remain stable during 2007–2017. However, the low SDI quintile and the greatest burden in South and East Asia, India, and Iran suggested that more targeted strategies should be performed in those regions and countries.

A report on the 73th Annual Congress of the Japan Society of Obstetrics and Gynecology International Workshop for Junior Fellows: Risk‐reducing surgery for hereditary breast and ovarian cancer

AbstractAt the 73rd Annual Congress of the Japan Society of Obstetrics and Gynecology, young doctors from Japan and South Korea made presentations on the present condition of risk‐reducing surgery for hereditary breast and ovarian cancer (RRSO) in their respective country. RRSO was insured in Japan in April 2020, whereas in South Korea, it was insured 7 years earlier in 2013. In Japan, certification criteria have been set for facilities that perform RRSO, and the number of facilities is increasing, but regional disparities still exist in its distribution. The number of gBRCA1/2 testing facilities is larger, and the cost is more affordable in South Korea than in Japan. Additionally, South Korea provides genetic counseling to a wider range of relatives compared to Japan. In the future, as the indications for the gBRCA1/2 test have expanded as a companion diagnostic for the use of PARP inhibitors, it is expected that the number of candidates for the gBRCA1/2 mutation test and RRSO will increase in Japan. It is important to increase the number of BRCA tests while maintaining the quality of genetic counseling in order to provide adequate information on BRCA mutations and RRSO for patients to support their decision. For the development of hereditary breast and ovarian cancer (HBOC) medical care, it is necessary to publish a nationwide database in Japan and continue to analyze and discuss the data based on the results.

Usefulness of the ‘cosmos pattern’ for differentiating between cervical gastric‐type mucin‐positive lesions and other benign cervical cystic lesions in magnetic resonance images

AbstractAimTo evaluate the usefulness of the ‘cosmos pattern’ (CP) on magnetic resonance (MR) images for differentiating between gastric‐type mucin‐positive lesions (GMPL) and gastric‐type mucin‐negative lesions (GMNL).MethodsThis study included 131 patients with clinical suspicion of lobular endocervical glandular hyperplasia (LEGH) who underwent pelvic MR imaging and a Pap smear and/or latex agglutination assay. Differences in MR findings, such as cyst and solid component patterns, cervical location and T1‐weighted image (T1WI) signal intensity, were compared between GMPL and GMNL. The diagnostic performances of the findings were assessed.ResultsThe frequencies of CP (63.1%), upper part (UP) lesions (72.3%) and hypointense area compared with the cervical stroma on T1WI (61.3%) were significantly greater in GMPL than in GMNL (P < 0.05). The sensitivity, specificity, positive predictive value, negative predictive value and odds ratio of the CP for diagnosis of GMPL were 63.1%, 87.9%, 83.7%, 70.7% and 12.4, respectively. In GMNL, a ‘macrocystic pattern’ was observed in 65.2% of patients; an isointense or hyperintense area on T1WI was observed in 86.4% of patients. The sensitivity was highest (90.8%) when one or more of the following were observed: CP, UP lesion, or hypointense area on T1WI. The specificity was highest (95.5%) when the CP was observed as a hypointense area on T1WI.ConclusionThe CP is a highly specific finding for diagnosis of GMPL. If the CP is observed as a hypointense area compared with the cervical stroma on T1WI, GMPL (i.e., LEGH or gastric‐type mucinous carcinoma) should be strongly suspected.

Erastin synergizes with cisplatin via ferroptosis to inhibit ovarian cancer growth in vitro and in vivo

AbstractAimCisplatin‐based chemotherapy is the first‐line treatment for ovarian cancer. However, acquired resistance to cisplatin treatment or serious side effects often occurs in ovarian cancer, and thus, there is an urgent need for effective and combined therapies to overcome such obstacles. In the present study, we aimed to uncover synergistic effects between erastin and cisplatin (CDDP) in inhibiting ovarian cancer cell growth by inducing ferroptosis in vitro and in vivo.MethodsWe performed a CCK‐8 assay to detect cell viability in response to erastin alone or in combination with cisplatin and provided further confirmation by western blotting analysis. Transmission electron microscopy and flow cytometry analysis were used to depict the characteristics of ferroptosis. In addition, an ovarian cancer tumor xenograft was built to verify the effects in vivo.ResultsCDDP induced multiple modes of cell death‐including ferroptosis in ovarian cancer cell lines. Mechanistically, erastin triggered ferroptosis and increased the levels of reactive oxygen species (ROS) so as to augment the cytotoxic effect of cisplatin. Combination therapy based on CDDP and erastin appeared to maximize the therapeutic effects while minimizing side effects in ovarian cancer both in vitro and in vivo.ConclusionCollectively, our results indicate that erastin works synergistically with cisplatin to inhibit ovarian cancer cell growth, which may be manipulated by a ROS‐mediated mechanism that enhances cisplatin therapy, and offers a novel strategy for overcoming cisplatin therapy resistance.

Clinical management of chemotherapy for elderly gynecological cancer patients

AbstractAimSince there are no established guidelines for the treatment of gynecological cancer in the elderly, medical treatment policy is currently decided by discussion with patients and their families based on doctors' experiences, referring to data from nonelderly patients and healthy elderly patients. The aim of this review was to clarify the current position of chemotherapy for elderly gynecological cancer patients and discuss the problems to be addressed in the future.MethodsLittle evidence has been accumulated for anticancer drug treatment in elderly individuals with gynecological cancer. This review presents outlines and representative papers on general cancer chemotherapy for the elderly, and problems that need to be solved in gynecological cancer fields in the future are identified.ResultsIn 2018, the American Society of Clinical Oncology (ASCO) published guidelines for “Practical Assessment and Management of Vulnerabilities in Older Patients Receiving Chemotherapy: ASCO Guideline for Geriatric Oncology Summary”. This guideline emphasizes that, when administering chemotherapy to patients over 65 years of age, vulnerabilities should be identified using geriatric assessment (GA). However, there have been no reports of clinical studies using GA in patients with cervical or uterine cancers, and only a few clinical studies using GA have been reported in patients with ovarian cancer.ConclusionsScoring systems suitable for elderly Japanese patients remain lacking. A Japanese gynecological GA needs to be developed in cooperation with other disciplines.

Role of FOXO protein's abnormal activation through PI3K/AKT pathway in platinum resistance of ovarian cancer

AbstractAimPlatinum‐based chemotherapy is the standard treatment for ovarian cancer. However, tumor cells' resistance to platinum drugs often occurs. This paper provides a review of Forkhead box O (FOXO) protein's role in platinum resistance of ovarian cancer which hopefully may provide some further guidance for the treatment of platinum‐resistant ovarian cancer.MethodsWe reviewed a 128 published papers from authoritative and professional journals on FOXO and platinum‐resistant ovarian cancer, and adopts qualitative analyses and interpretation based on the literature.ResultsOvarian cancer often has abnormal activation of cellular pathways, the most important of which is the PI3K/AKT pathway. FOXOs act as crucial downstream factor of the PI3K/Akt pathway and are negatively regulated by it. DNA damage response and apoptosis including the relationship between FOXOs and ATM‐Chk2‐p53 are essential for platinum resistance of ovarian cancer. Through gene expression analysis in platinum‐resistant ovarian cancer cell model, it was found that FoxO‐1 is decreased in platinum‐resistant ovarian cancer, so studying the role of FOXO in the pathway on platinum‐induced apoptosis may further guide the treatment of platinum‐resistant ovarian cancer.ConclusionsThere are many drug resistance mechanisms in ovarian cancer, wherein the decrease in cancer cells apoptosis is one of the important causes. Constituted by a series of transcription factors evolving conservatively and mainly working in inhibiting cancer, FOXO proteins play various roles in cells' antitumor response. More and more evidence suggests that we need to re‐understand the role that FOXOs have played in cancer development and treatment.

Estrogen‐related receptor alpha copy number variation is associated with ovarian cancer histological grade

AbstractAimCopy number variations (CNVs) are related to the genetic and phenotypic diversity of cancers and identifying genetic alterations could improve treatment strategies. Here, we used The Cancer Genome Atlas (TCGA) to explore associations between estrogen‐related receptor alpha (ESRRA) CNVs and histological grade in patients with ovarian cancer (OC).MethodsGene expression data and clinical information of 620 OC patients were obtained from The Cancer Genome Atlas）TCGA and associations between ESRRA CNVs and clinical characteristics were evaluated. Multivariate logistic regression analyses to obtain odds ratios (ORs) using a 95% confidence interval (CI) were performed, adjusting for race, age, histological grade, and tumor size.ResultsESRRA CNVs were associated with histological grade (OR 0.6235 [95% CI, 0.3593–0.8877]; p < 0.05) and peroxisome proliferator‐activated receptor gamma coactivator 1‐alpha (PPARGC1A) CNVs (OR −0.6298 [95% CI, −0.9011 to −0.3585]; p < 0.05). In multivariate analyses, ESRRA CNVs remained significantly associated with histological grade (OR 0.6492 [95% CI, 0.3549–0.9435]; p < 0.05) and PPARGC1A CNVs (OR −0.6236 [95% CI, −0.9269 to 0.3203]; p < 0.05).ConclusionThere was a significant association between ESRRA CNVs in patients with OC and histological grade of the cancer.

Diagnostic performance of immediate colposcopy among women with high‐risk human papillomavirus (HPV) other than HPV 16/18 and normal cytology

AbstractAimPersistent infection with 1 of 14 high‐risk genotypes human papillomavirus (HPV) genotypes is the crucial for the development of high‐grade cervical cancer precursors. The reassuring management of women with cytology negative, high‐risk HPV (HrHPV) positive is important especially after the widespread use of HPV testing either as a cotest. The aim of our study was to compare the colposcopic biopsy results of women with HPV 16/18 with other Hr‐HPV genotypes and determine positive predictive values (PPV) for CIN2+ of other HR HPV genotypes.MethodsWe prospectively had included the women with negative cytology and positive Hr‐HPV test other than HPV 16/18. Control group was composed of women with negative cytology positive test results for either HPV 16 or HPV 18. Women with HrHPV positive, cytology negative referred to immediate colposcopy.ResultsThe prevalence of CIN1 and CIN2 is significantly higher in HPV 16/18 group than pooled other HrHPV group (34.1% vs 17.5%, P = 0.01 for CIN 1+; 14.8% vs 5.2%, P = 0.03 for CIN 2+). The prevalence of CIN3 was almost three fold in women with HPV 16/18 (9.1% vs 3.1%). PPV for CIN 2+ was 16.4 (9.1–27.3) for HPV 16, 11.7 (2–37.7) for HPV 18, 20 (3.5–55.7) for HPV 31, 11.1 (0.6–49.3) for HPV 51, 12.5 (0.6–53.3) for HPV 58 and 59.ConclusionWe showed the relative high PPV for CIN2+ in OHrHPV other than HPV 16/18 positive group among cytology negative population. HPV 33, 51, 58, 59 and 18 had similar PPV for CIN2+ in basal cytology negative population.

Hypersensitivity reaction to pegylated liposomal doxorubicin administration for Mullerian carcinoma in Japanese women

AbstractAimPEGylated liposomal doxorubicin (PLD) is a therapeutic agent for gynecological malignancy. Hypersensitivity reaction (HSR) is a major adverse effect that usually disappears after halting administration of PLD. Premedication is usually not necessary before administration of PLD to prevent HSR. Here, we evaluated the frequency of HSR during administration of PLD following premedication in Japanese women.MethodsWe performed PLD administration in 78 patients (386 cycles) between 2013 and 2018. Granisetron hydrochloride and dexamethasone sodium phosphate were administered 30 min before PLD administration. Then, PLD (40 or 30 mg/m2 combined usage with carboplatin) was administered. We retrospectively reviewed the medical records of 78 patients and examined the frequency of HSR.ResultsSeven of 78 (9%) patients showed HSR by PLD administration following premedication. One patient showed cardiopulmonary arrest in 13 min after PLD administration (grade 4). The other six patients showed grade 2 HSR. All patients developed HSR in the first course. The incidence of HSR was significantly higher in patients with allergic history than in patients without allergic history (p = 0.0151).ConclusionsClinicians should be aware of the potential for HSR in patients administered PLD, particularly those with allergic history and those receiving the first cycle of PLD, even following premedication.

Application of serum markers in diagnosis and staging of ovarian endometriosis

AbstractAimsLaparoscopic surgery is widely used for diagnosing ovarian endometriosis but it has medical risks. This study explored the application of blood indicators in diagnosis and staging of ovarian endometriosis, aiming to develop a noninvasive diagnostic method.MethodsA total of 190 ovarian endometriosis patients were included in observation group, among these participants, 77 patients among them were stages I–II, and the rest 113 patients were stages III–IV, and a total of 103 healthy women as control group. Serum biochemical indexes, tumor markers, and cytokines levels in two groups were used for the diagnosis and staging of the disease. Area under the receiver operating characteristic (ROC) curve (AUC) predicted the value of individual and joint tests for indicators.ResultsBiochemical indexes, namely, alkaline phosphatase (ALP), total protein (TP), and glucose (Glu) could distinguish patients from normal women; and that ALP and Glu could indicate disease staging. In tumor markers, alpha fetoprotein (AFP), carcinoembryonic antigen (CA) 125, CA199 and human epididymis protein 4 (HE4) helped to diagnose endometriosis; CA125, HE4, and cytokeratin 19 fragment (CYFRA21‐1) could differentiate stages. In cytokines, vascular endothelial growth factor (VEGF), tumor necrosis factor (TNF)‐α, interleukin (IL)‐6, soluble fms‐like tyrosine kinase receptor 1 (sflt‐1), monocyte chemoattractant protein (MCP)‐1 therefore, have values to diagnose endometriosis; VEGF, TNF‐α, IL‐6, and sflt‐1 helped to differentiate disease staging.ConclusionSerological indicators in ovarian endometriosis patients were different from healthy women, which were of certain differential values in diagnosis and disease staging. The current study provided a novel strategy for endometriosis diagnosis.

Clinical Utility of the REM Score in Stratifying Endometrial Malignancy Risk: Insights From a Tertiary Care Centre in South India

ABSTRACT Objective To evaluate the performance of the risk of endometrial malignancy (REM) scoring system using its existing cut‐off value (0.3185) in stratifying risk for endometrial malignancy and to determine an optimal cut‐off value in a tertiary care setting in South India. Methods This cross‐sectional diagnostic accuracy study enrolled 220 women aged 40–80 years who underwent surgical interventions for abnormal uterine bleeding (AUB), postmenopausal bleeding (PMB), or ultrasonographic abnormalities. Data on clinical, ultrasonographic, and biochemical parameters (including HE4 levels) were collected, and REM scores were calculated. Histopathological outcomes served as the gold standard for assessing performance. Results The median REM score was significantly higher in women with malignancy (0.5581, IQR: 0.3442–0.7489) compared to those without (0.1709, IQR: 0.0993–0.3628, p  < 0.001). At the existing cut‐off value (0.3185), the sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were 79.6%, 72.67%, 51.65%, and 90.7%, respectively. An optimal cut‐off value of 0.3348 demonstrated improved sensitivity and specificity in the study population. Conclusion The REM scoring system effectively stratifies patients at high risk for endometrial malignancy. Adjusting the cut‐off value for this population may further enhance its diagnostic utility.

What is the impact of corpus uterine invasion on oncologic outcomes in surgically treated cervical cancer?

AbstractAimTo investigate the clinical significance of uterine corpus involvement in patients with surgically treated cervical cancer.MethodsPatients (n = 354) with clinical early‐stage (stage IB1‐IIA2) cervical cancer who underwent radical hysterectomy and pelvic ± paraaortic lymphadenectomy were evaluated.ResultsUterine invasion was detected in 60 (16.9%) patients. Patients with uterine invasion had a higher rate of pelvic lymph node metastasis than those without uterine invasion (35% vs 22.8%, p = 0.046). In multivariate analysis, no statistically significant difference was identified between patients with and without uterine invasion for pelvic lymph node metastasis (p = 0.953). Uterine invasion was identified as an independent risk factor for paraaortic lymph node metastasis in multivariate analysis (p = 0.012). The presence of pelvic lymph node metastasis was found to be another significant predictor of paraaortic lymph node involvement (p = 0.022). In addition, uterine invasion and lymph node metastasis were identified as an independent risk factors regarding poor prognosis in cancer‐specific survival (hazard ratio [HR]: 4.537; 95% confidence interval [CI], 1.304–15.782; p = 0.017 and HR: 5.598; 95% CI, 1.581–19.823; p = 0.008, respectively).ConclusionsUterine invasion is an independent predictor of decreased survival and the presence of paraaortic lymph node metastasis in cervical cancer. The presence of the uterine invasion in cervical cancer should be considered as a poor prognostic factor in the decision of treatment.

Study on the effect and mechanism of NFKBIA on cervical cancer progress in vitro and in vivo

AbstractAimNFKBIA is frequently encountered. However, its expression and relevance of the proliferation, invasion, and migration in human cervical cancer (CC) remain unclear. The role and novel mechanism of NFKBIA in CC progression were investigated in this study.MethodsWe analyzed the expression of NFKBIA in CC and adjacent normal tissues and explored the proliferation, migration, and invasion of HeLa cells by treating with either wild‐type NFKBIA plasmid or NFKBIA siRNA. Effect of NFKBIA on the epithelial‐mesenchymal transition (EMT) and the β‐catenin‐mediated transcription of target genes were evaluated subsequently.ResultsNFKBIA expression was lower in CC tissues than that of adjacent tissues. An obvious dysregulation of NFKBIA overexpression was revealed in CC cell proliferation, invasion, and migration, which differed from the effect of knockdown NFKBIA. NFKBIA overexpression facilitated the expression of both phosphorylated β‐catenin and E‐cadherin protein. It inhibited the expression of vimentin, TWIST, as well as downstream targets of β‐catenin including c‐MYC, TCF‐4 and MMP14. Conversely, NFKBIA silencing elevated the expression of c‐MYC, TCF‐4, and MMP14, and promoted the EMT in HeLa cells. Both endogenous and exogenous NFKBIA interacted with β‐catenin. Moreover, β‐catenin overexpression stemmed effects of NFKBIA on the proliferation, migration, and invasion of HeLa cells. By overexpressing NFKBIA in vivo, the volume and size of tumors were notably decreased, while no obvious alteration was found in mice body weight.ConclusionBy inhibiting β‐catenin‐mediated transcription, NFKBIA functioning as a tumor suppressor might be introduced as a novel anti‐metastatic agent for the treatment of targeted CC.

Laparoscopic repair of segmental obturator nerve injury defect using an artificial nerve conduit: A case report

AbstractObturator nerve injury is an uncommon complication frequently associated with pelvic gynecologic or urologic cancer surgery. It can lead to disability or adversely affect quality of life. Large segmental defects are particularly difficult to manage as the limited mobility of the nerve prevents tension‐free direct end‐to‐end anastomosis. A 36‐year‐old woman with cervical cancer underwent sentinel lymph node biopsy, laparoscopic radical hysterectomy, and bilateral adnexectomy. During the procedure, the sentinel lymph node (right obturator node) adherent to the obturator nerve was resected together with the nerve segment leaving a 3 cm defect. Immediate laparoscopic obturator nerve repair was performed using an artificial nerve conduit leading to successful recovery. We report this unique case due to rarity of large segmental obturator nerve defects and present laparoscopic nerve repair with artificial nerve conduits as a useful treatment alternative of these important injuries, without nerve donor site morbidity.

Human papillomavirus genotyping predicts residual/recurrent disease after local treatment for cervical intraepithelial neoplasia better than viral DNA testing

AbstractAimType‐specific persistent infection (TSPI) of human papillomavirus (HPV) is reportedly associated with a high risk of residual/recurrent disease after local treatment for cervical intraepithelial neoplasia (CIN). This study aimed to evaluate whether HPV genotyping is more accurate in detecting residual/recurrent disease than HPV DNA testing and identify which HPV genotype can predict a high risk of residual/recurrent disease.MethodsWe retrospectively reviewed patient outcomes and results of HPV DNA testing and genotyping at 6–12 months after local treatment for CIN2/3 for 439 women. We investigated residual/recurrent disease occurrence according to the TSPI and new infections. Sensitivity, specificity, and positive and negative predictive values (PPV and NPV, respectively) of the two testing methods for predicting residual/recurrent diseases were also evaluated.ResultsEighty‐five (19.4%) patients were positive for HPV DNA testing after treatment, of which 74 (87.1%) had TSPI. Residual/recurrent disease was identified in 34 (7.7%) patients, of which 30 were positive for HPV DNA testing and had TSPI of HPV16, 18, 31, 33, 52, and 58 (six HPV genotypes). The sensitivity and NPV of HPV DNA testing and TSPI were equal at 88.2% and 98.9%, respectively. The specificity and PPV of TSPI were higher than those of HPV DNA testing (89.1% vs. 86.4%, 40.5% vs. 35.2%, respectively). Furthermore, the TSPI of the six HPV genotypes further improved specificity (90.6%) and PPV (44.1%) with the same sensitivity and NPV.ConclusionHPV genotyping is more useful than HPV DNA testing for determining TSPI, especially of the six HPV genotypes.

Human papillomavirus sequencing reveals its usefulness for the management of HIV‐infected women at risk for developing cervical cancer

AbstractAimNext‐generation sequencing (NGS) is able to describe the composition of human papillomaviruses (HPVs) as percent (%) reads rather than positive/negative results. Therefore, we used this unique approach to assess the prevalence of cervical HPVs of HIV infected (HIV+) in order to understand the determinants of being infected with higher % reads of high risk (HR)‐HPVs and cervical abnormalities of atypical squamous cells of unknown significance or higher (ASCUS+).MethodsStudy included 66 women characterized for relevant risk factors/cytology. Receiver‐operating curve curve was used to derive the optimal % read cut point to identify ASCUS+ in relation to any HR‐HPV genotype or other specific HPV genotypes. The determinants of ASCUS+ and HR‐HPVs were tested using logistic regression.ResultsWomen with >20% reads of any HR‐HPV or >12% any HR‐HPV other than HPV 16/18 were 5.7 and 12.6 times more likely to be diagnosed with ASCUS+, respectively. Lower CD4 count was a significant determinant of >20% reads of HR‐HPV (odds ratio [OR] = 4.1) or >12% any HR‐HPV other than HPV 16/18 (OR = 4.5).ConclusionWe envision that the NGS‐based HPV detection will be more accurate for screening and management of HIV+ at risk for developing cervical cancer (CC). We raise concerns regarding the limitations of 16/18‐based HPV testing for triage and the efficacy of current HPV vaccines for preventing CC in HIV+.

Uterine Mapping for Lymph Node Metastasis in Endometrial Cancer: A Multicenter Retrospective Cohort Study

ABSTRACT Aim To evaluate the association between uterine tumor localization and lymph node metastasis (LNM) in endometrial cancer through pathological uterine mapping. Methods This multicenter retrospective cohort study included 427 patients with endometrial carcinoma who underwent total hysterectomy, bilateral salpingo‐oophorectomy, and systematic lymphadenectomy. Tumor localization was classified based on a six‐site pathological mapping model: isolated lower uterine segment (LUS), LUS + corpus, corpus‐only, corpus+fundus, fundus‐only, and total uterine cavity. LNM patterns and pathological features were compared across sites. Logistic regression was used to determine independent predictors of LNM. Results The highest LNM rates were observed in tumors involving the LUS + corpus (37.0%) and total uterine cavity (32.4%), whereas the lowest rate was seen in corpus‐only tumors (10.2%) ( p  < 0.001). Tumors in high‐risk sites featured significantly higher rates of deep myometrial invasion, substantial LVSI, and high‐grade histology. In multivariate analysis, substantial LVSI (OR: 9.2, p  < 0.001), any LUS involvement (OR: 2.6, p  = 0.001), aggressive histology (OR: 2.1, p  = 0.017), and BMI (OR: 1.08, p  = 0.025) independently predicted LNM. Conclusions Pathological uterine mapping reveals that LUS involvement is an independent risk factor for lymphatic dissemination in endometrial cancer. Tumor site classification may enhance preoperative risk stratification and guide individualized surgical strategies.

High neutrophil‐to‐lymphocyte ratio is a predictor of short‐term survival for patients with recurrent cervical cancer after radiation‐based therapy

AbstractAimPatients with recurrent cervical cancer after radiotherapy have poor prognoses because of the lack of effective treatment options. Biomarkers to predict survival outcomes for recurrent cervical cancer are warranted because patients with limited life expectancy sometimes benefit from less aggressive treatment in combination with early palliative care. Therefore, we aimed to explore a predictive biomarker for the outcomes of patients with recurrent cervical cancer.MethodsWe retrospectively investigated 231 patients initially treated with radiation‐based therapy between January 2004 and December 2015. The associations between clinicopathological features at the time of relapse and overall survival after relapse were assessed. As factors which reflect patients' conditions, we particularly focused on C‐reactive protein‐to‐albumin ratio (CAR) and neutrophil‐to‐lymphocyte ratio (NLR) at the time of relapse. Additionally, we investigated biomarkers predictive of short‐term survival.ResultsAmong 231 patients, 91 patients experienced relapse and 74 patients died during the follow‐up period. Multivariate analysis revealed that treatment after relapse, CAR, and NLR was significantly associated with overall survival. Among them, treatment after relapse significantly affected survival outcomes, and patients who received definitive local treatment had a better 3‐year survival rate than those who received other treatments. Conversely, NLR was the most influential biomarker for short‐term survival, and the prognosis of patients with high NLRs was much worse than those with low NLRs.ConclusionsThis study thus demonstrated that, for the patients with recurrent cervical cancer who received radiation‐based therapy, definitive local treatment can provide long‐term survival and extremely high NLRs are predictive of short‐term survival.

Validation of the FIGO 2018 staging system of cervical cancer: Retrospective analysis of FIGO 2009 stage IB1 cervical cancer with tumor under 2 cm

AbstractAimThe International Federation of Gynecology and Obstetrics (FIGO) revised the cervical cancer staging system in 2018. This study aims to validate the revised staging system in patients with tumors <2 cm in size who were classified as FIGO 2009 stage IB1.MethodsWe evaluated 62 women with stage IB1 cervical cancer (FIGO 2009) who underwent radical hysterectomy as the initial treatment between November 2004 and August 2018 in our institution. The patients with FIGO 2009 stage IB1 and tumors <2 cm in size were enrolled. We reclassified their stage according to the FIGO 2018 staging system and analyzed their clinicopathological data retrospectively.ResultsTwenty‐five patients met the inclusion criteria. According to the FIGO 2018 classification, 9 (36.0%) patients were classified as stage IA, 13 (52.0%) as stage IB1, and 3 (12.0%) as stage IIIC, respectively. One (11.1%), six (46.2%), and three (100%) patients with lymphovascular space invasion were classified as stage IA, IB1, and IIIC, respectively. No significant differences were found in the 5‐year overall survival or progression‐free survival among the three stages.ConclusionsAs many as 36.0% of patients classified as FIGO 2009 stage IB1 with a tumor <2 cm in size were classified as stage IA in the FIGO 2018 classification. For these cases, a treatment less invasive than radical hysterectomy or radiotherapy might be sufficient. Our results suggest that cervical cancer patients with tumors <2 cm should be carefully diagnosed by performing cervical conization and assessed the pathological findings before hysterectomy.

Clinical characteristics of bowel mucosal invasion in epithelial ovarian cancer

Abstract Aim Bowel mucosal invasion in epithelial ovarian cancer (EOC) is classified as stage IVB disease. However, the reason for this classification remains unclear, and the clinical outcomes of bowel mucosal invasion in EOC warrant further investigation. Therefore, we aimed to examine patients with EOC presenting with bowel mucosal invasion and evaluate the validity of the current classification. Methods We retrospectively reviewed data from patients with stage IVB EOC who presented with bowel mucosal invasion at our hospital between January 2015 and September 2023. Patients with bowel mucosal invasion and other factors associated with stage IVB EOC were excluded. The primary and secondary endpoints were progression‐free survival (PFS) and overall survival (OS), respectively. Results Among 226 patients diagnosed with stage IVB EOC, 22 (9.7%) exhibited bowel mucosal invasion and 13 (5.8%) were diagnosed with stage IVB EOC based solely on the presence of bowel mucosal invasion. The median follow‐up period was 40.5 months (range, 14.9–81.6 months). Primary debulking surgery was performed in nine patients (69.2%) and neoadjuvant chemotherapy‐interval debulking surgery in four (30.8%). Complete resection was achieved in all 13 patients without other stage IVB‐related factors. Among them, the 3‐year PFS and OS rates were 54.9% and 82.1%, respectively. Conclusion In cases of bowel mucosal invasion, complete resection appears feasible and may be associated with a more favorable prognosis compared with that of the overall stage IVB population. Therefore, bowel mucosal invasion alone may not represent a potential prognostic factor for stage IVB ovarian cancer.

Novel Subtype Classification of Diffuse Uterine Leiomyomatosis Based on a Nationwide Survey in Japan

ABSTRACT Aim Diffuse uterine leiomyomatosis (DUL) is characterized by numerous uterine leiomyomas within and diffusely replacing the myometrium. However, because of its rarity, the prevalence, diagnostic criteria, and standard treatment for patients with DUL who wish to preserve their fertility remain unknown. This study aimed to clarify the current status of the diagnosis of DUL in Japan. Methods We conducted a web‐based survey targeting 1080 Obstetrics and Gynecology training institutions registered with the Japanese Medical Specialty Board. We asked them whether they had treated patients with DUL over the past 10 years (2013–2022). We obtained magnetic resonance imaging (MRI) scans from institutions that reported clinical experience with DUL, and conducted a central review to determine whether each case was consistent with DUL. We also investigated whether DUL could be classified into subtypes. Results Responses were obtained from 428 institutions, of which 128 reported clinical experience with DUL or DUL‐like multiple uterine leiomyomas, totaling 653 cases. MRI scans from 408 cases were centrally reviewed by a subcommittee, and 307 cases were confirmed as DUL. Based on the imaging characteristics, DUL was classified into three subtypes: total replacement, myometrial replacement, and submucosal‐dominant. Conclusions This survey revealed that 653 cases of DUL or DUL‐like multiple uterine leiomyomas were managed over a 10‐year period in Japan. Based on a central review of MRI scans, DUL can be classified into three distinct subtypes. Given the differences between these subtypes, treatment approaches for patients wishing to preserve fertility may vary, highlighting the need for further investigation.

Low erythrocyte folate levels and increased risk of invasive cervical cancer in Chinese women

AbstractAimTo investigate the relationship between erythrocyte folate levels and cervical lesions.MethodsUsing a case–control method, patients with cervical lesions from September 2021 to February 2022 in the Department of Obstetrics and Gynecology, Jiangnan University Hospital were selected as study subjects. After cervical biopsy, 40 cases of cervical intraepithelial neoplasia (CIN) CIN3 and 65 cases of cervical cancer as case group. The normal population of 120 cases attending the same period served as the control group. A competitive model was used to establish a chemiluminescence immunoassay (CLIA) for human erythrocyte folate. Erythrocyte folate levels of 225 subjects were determined.ResultsSerum folate levels were 7.82 ± 3.13, 8.04 ± 3.58, and 7.58 ± 4.30 ng/ml in the control, CIN3, and cervical cancer groups, with no statistically significant differences (p = 0.959). Erythrocyte folate levels were 307.27 ± 122.95, 306.52 ± 189.77, and 285.42 ± 125.74 ng/ml, respectively, with statistically significant differences (p = 0.03).ConclusionsIn a population of middle‐aged Chinese women, the lower the erythrocyte folate value, the greater the risk of cervical cancer. In addition, serum folate levels were not associated with cervical lesions.

Machine Learning–Predictive Models for Survival in Uterine Cancer Patients With Type 2 Diabetes: A Territory‐Wide Cohort Study

ABSTRACT Aim This study aimed to develop predictive models and establish a risk scoring system to identify risk factors associated with survival in uterine cancer patients with type 2 diabetes (T2D) and estimate their survival probabilities. Methods Data were collected from the Hong Kong Hospital Authority Data Collaboration Laboratory (HADCL) from 2000 to 2020. Cox proportional hazards regression, survival tree, LASSO Cox regression, boosting, and random survival forest (RSF) were utilized to develop predictive models for survival. Key risk factors were identified through Shapley Additive Explanations analysis, whereas the AutoScore‐Survival package facilitated the development of a risk scoring system. Results This cohort study included 2047 uterine cancer patients with T2D. The average survival time was 100.82 (standard deviation: 72.75) months. The RSF model demonstrated the strongest predictive performance, achieving a time‐dependent area under the curve (AUC) of 0.823 and a C ‐index of 0.90. A risk scoring system was created based on several criteria: age at cancer diagnosis, duration of T2D, creatinine levels, serum potassium level, low‐density lipoprotein cholesterol level (LDL‐C) level, body mass index (BMI), and triglycerides level. This scoring system classified 31.4% of patients as high‐risk, resulting in a 5‐year survival probability of 43.5%, about 1.7 times lower than that of the low‐risk group. Conclusion This study leveraged machine learning to identify key survival predictors and develop a clinically interpretable risk scoring system for uterine cancer patients with T2D. Key predictors, including age at cancer diagnosis, duration of T2D, creatinine levels, serum potassium levels, LDL‐C levels, BMI, and triglycerides levels, effectively stratified survival risk. These findings demonstrate the potential of data‐driven models to enhance individualized prediction and inform targeted clinical management.

Management of diffuse uterine leiomyomatosis for fertility preservation: Case series and systematic literature review

AbstractAimThe aim of this study was to evaluate the surgical, reproductive, and perinatal outcomes of patients with diffuse uterine leiomyomatosis desiring fertility preservation.MethodsPatients diagnosed with diffuse uterine leiomyomatosis based on magnetic resonance imaging at Kindai University Hospital between 2017 and 2024 were included in a case series. A systematic literature review on diffuse uterine leiomyomatosis desiring fertility preservation was carried out.ResultsThe case series showed that fertility preservation was desired in 8 of 18 cases, of which 1 was conceived after assisted reproductive technology and underwent cesarean section at 34 weeks of gestation for placenta previa accreta. A systematic literature review identified 31 cases from descriptive observational studies (1–8 cases per study). Although more fibroids (n = 87) were enucleated by extensive myomectomy than by hysteroscopic myomectomy (n = 33) (p < 0.0001), extensive myomectomy was often associated with massive blood loss and blood transfusion. Perinatal complications were more frequent in extensive myomectomy (5/7) compared to hysteroscopic myomectomy (2/12, p = 0.04). Preterm delivery before 36 weeks was more frequent in extensive myomectomy (4/6 cases) than in hysteroscopic myomectomy (1/11 cases, p = 0.03).ConclusionFertility preservation in diffuse uterine leiomyomatosis was previously considered difficult, but it is now recognized to be possible. Hysteroscopic myomectomy is a minimally invasive option. If conception is not achieved, extensive myomectomy may be considered. However, extensive myomectomy is more invasive, with a higher risk of perinatal complications. Large‐scale clinical trials are required to establish a management standard for diffuse uterine leiomyomatosis.

LncRNA TTC28‐AS1 promotes the progression of cervical cancer by targeting miR‐377‐3p

AbstractAimCervical cancer (CC) is the fourth most common malignancy affecting women worldwide and has a poor prognosis. The aim of this study was to investigate the clinical significance and mechanism of TTC28‐AS1 in CC.MethodsA total of 120 individuals suffering from CC were included in this study. RT‐qPCR was used to detect the level of TTC28‐AS1, and the prognostic value of TTC28‐AS1 was analyzed by Kaplan–Meier curve and Cox regression analyses. Dual‐Luciferase reporter assay was used to verify the targeting relationship between TTC28‐AS1 and miR‐377‐3p. The proliferative ability of CC cells was detected by CCK‐8 kit. The migration and invasion of CC cells were detected by transwell system.ResultsThe expression level of TTC28‐AS1 was elevated in patients with CC, serving as an indicator of unfavorable clinical outcome. TTC28‐AS1 may promote the proliferation, migration, and invasion of CC cells by targeting miR‐377‐3p.ConclusionsTTC28‐AS1 has the potential to promote the malignant progression of CC by targeting miR‐377‐3p, thus emerging as a promising therapeutic target for the treatment of CC.

Lack of knowledge, not vaccine hesitancy, is the main cause of low human papilloma virus vaccination rate among systemic lupus erythematosus patients in Japan after suspension of proactive recommendation: Analysis of a patients' survey

AbstractObjectiveTo identify the factors that inhibit human papilloma virus (HPV) vaccination to improve the high HPV infection rate and cervical cancer incidence among SLE patients.MethodsWe conducted a questionnaire survey of female SLE patients aged 18–45 years attending our hospital to analyze factors related to HPV vaccination.ResultsWe obtained responses of 88 participants. Only 5 (5.7%) were received HPV vaccination, 15 (17.0%) were uncertain of their vaccine history, and 27 (30.7%) had never even heard of HPV vaccination. The reasons for unvaccinated against HPV were “don't know” with 24 participants, “missed opportunity” with 15, and “troublesome, somehow” with 8. The most trusted source of medical information for the unvaccinated was their physician (69, 60.2%). Among the unvaccinated, those who wished to be vaccinated in the future were positively correlated with “trust of vaccine benefit” (r = 0.561, p = 0.005) and “general knowledge about HPV vaccine” (r = 0.512, p = 0.013), and negatively correlated with “negative attitudes toward vaccination and vaccine policy” (r = −0.547, p = 0.007).ConclusionHPV vaccination rate among SLE patients in Japan was extremely low. The main reason was lack of knowledge. The most effective solution is considered to provide accurate information and adequate recommendations of HPV vaccination by attending physicians.

Short‐term relugolix use for rapidly growing uterine fibroids before uterus‐preserving surgery in women seeking to conceive: Two case reports

AbstractLarge uterine fibroids that grow rapidly over a short period should be differentiated from uterine leiomyosarcoma, and their treatment remains controversial in women seeking to conceive. Here, we report two cases of uterine fibroids treated with short‐term relugolix administration followed by myomectomy. Needle biopsy specimens obtained before relugolix administration showed no malignancy, and significant tumor shrinkage was observed following treatment. Both patients subsequently underwent myomectomy. One patient achieved a live birth 14 months after myomectomy, whereas the other experienced improvement in severe anemia, allowing her to prepare for pregnancy. Histological examination after relugolix administration revealed atrophic changes in spindle cells within the fibroids, characterized by nuclear crowding and decreased immunoreactivity for desmin and α‐smooth muscle actin. The significant fibroid shrinkage observed after the short‐term administration of relugolix provided a rationale for myomectomy, improved anemia, and facilitated appropriate uterine reconstruction, ensuring structural integrity for future pregnancies in women of reproductive age.

Uterine Tumor Resembling Ovarian Sex Cord Tumor ( UTROSCT ) With a GREB1 ‐ NCOA2 Fusion: A Case Report and Diagnostic Considerations

ABSTRACT Uterine Tumor Resembling Ovarian Sex Cord Tumor (UTROSCT) is a rare mesenchymal neoplasm with uncertain malignant potential. We report a 37‐year‐old woman with menorrhagia, initially suspected as a leiomyoma on MRI. Hysteroscopic resection revealed an infiltrative tumor with cords, glands, and spindle cells showing mild‐to‐moderate atypia. Immunohistochemistry was positive for ER, PR, WT‐1, Calretinin, and FOXL2. RNA‐based NGS identified the GREB1‐NCOA2 fusion. Despite treatment, the patient died from metastases within 24 months. This case highlights UTROSCT's aggressive potential in young patients and underscores the diagnostic utility of molecular testing (e.g., GREB1 rearrangements) to distinguish it from mimics like LG‐ESS. The fatal outcome suggests GREB1‐NCOA2 may correlate with high‐risk behavior, warranting close follow‐up.

Retrospective analysis of treatment and prognosis for clear cell carcinoma of the uterine cervix: 15‐year experience at a single institution

AbstractAimClear cell carcinoma of the uterine cervix (CCCUC) is a rare disease, accounting for 4% to 9% of cervical adenocarcinomas. Because it is so rare, its pathogenesis is largely unknown, and the standard treatment is unclear due to a lack of prospective studies. Our aim is to investigate the clinical features, treatment, and prognosis of CCCUC.MethodsWe retrospectively evaluated the clinical characteristics, treatment choices, and outcomes of 12 patients with CCCUC treated at our institution between January 2009 and July 2024.ResultsThe median patient age was 62.5 years (range, 14–90 years). The most common stage was IB (IA, n = 3; IB, n = 4; IIB, n = 1; IIIC, n = 2; IVB, n = 2). Ten patients underwent surgery as initial treatment: 6 underwent radical hysterectomy plus pelvic lymphadenectomy (PLD) or sentinel lymph node biopsy (SLNB), with or without para‐aortic lymphadenectomy (PALD); 3 underwent modified radical hysterectomy plus PLD with or without PALD; and 1 underwent radical trachelectomy with SLNB as fertility‐preserving surgery. All patients underwent bilateral salpingo‐oophorectomy except for the patient who opted for radical trachelectomy. Five patients received adjuvant treatment: 3 received platinum‐based systemic chemotherapy (2 of whom had combination therapy with bevacizumab), and 2 received concurrent chemoradiotherapy. The median follow‐up was 43.5 months (range, 1–123 months). The 5‐year progression‐free survival rate was 64.5%.ConclusionSystemic platinum‐based chemotherapy with bevacizumab may be more effective than concurrent chemoradiotherapy as adjuvant therapy for CCCUC.

Association between low‐grade cervical cytology and histological cervical intraepithelial neoplasia concurrent vaginal intraepithelial neoplasia among outpatient colposcopy: A retrospective study

AbstractBackgroundThere is evidence that cytological low‐grade squamous intraepithelial lesion (LSIL) is associated with cervical intraepithelial neoplasia (CIN) in colposcopy, but its link to cervical intraepithelial neoplasia concurrent vaginal intraepithelial neoplasia (VaIN) remains unclear.MethodsA retrospective chart review was performed that encompassed patients who were pathologically diagnosed with CIN at a single center from 2017 to 2021. Demographics, referring cytology, HPV genotype, and histologic information were recorded. The primary outcome was CIN coexisted with VaIN.ResultsAmong 5488 patients included in this study (mean age, 37.0 years [SD 10]; 1376 [25.4]) had low‐grade cervical cytology positive. A total of 458 participants were classified as having histologically CIN concurrent VaIN. Compared with participants without LSIL cytology, those with LSIL cytology had a higher prevalence of histological CIN concurrent VaIN (38.1% [172] vs. 24.2% [1204]). After adjusting for potential confounders, we found an association between LSIL cytology and histological CIN concurrent VaIN (odds ratio [OR], 3.28; 95% confidence interval [CI], 1.84–5.82). In subgroup analyses, LSIL cytology was associated with histological CIN concurrent VaIN among participants sexual life year 10 to 19 years (OR, 5.35; 95% CI, 1.58–18.04), gravidity 1–2 fetus (OR, 5.49; 95% CI, 1.62–18.61), HPV33 positive (OR, 90.06; 95% CI, 2.27–3579.46), HPV52 positive (OR, 9.09; 95% CI, 1.96–42.12).ConclusionsIn this cross‐sectional study, LSIL cytology was associated with histological CIN concurrent VaIN in the outpatient colposcopy in adjusted models. This association may be important to consider in the colposcopy for the early detection of CIN concurrent VaIN.

A rare case of numerous parasitic myomas after laparoscopic myomectomy

AbstractParasitic myoma is a relatively rare disease in which one or more leiomyomas form outside the uterus; however, the detailed causes are unknown. Few sporadic reports are available, and per our research, the maximum number of parasitic myomas reported to date was 26, and almost all cases were treated by surgical resection. We report a rare case of numerous parasitic myomas in the abdominal cavity, possibly including an intrathoracic lesion, which could not be resected completely. The patient was a 42‐year‐old, gravid 2, para 0, artificially aborted 2, and not yet menopausal woman. She had undergone laparoscopic myomectomy at a different hospital 6 years prior. Laparoscopically, numerous hard white masses, ranging from 1 mm to approximately 55 mm in size, were found in the abdominal cavity. The masses were particularly numerous in the omentum and mesentery but were also found on the diaphragm, abdominal peritoneum, and intestinal surface. The patient was pathologically diagnosed with multiple benign leiomyomas. On computed tomography, a similar nodule was observed in the right lower lobe of the lung. Despite using in‐bag morcellation, as in this case, numerous parasitic myomas occurred, suggesting that greater caution should be exercised when explaining laparoscopic myomectomy to patients.

The relationship between imaging‐based body composition parameters and disease prognosis in patients with endometrial cancer

Abstract Background Obesity is known as a risk factor for endometrial cancer (EC). Only a few studies investigate the relationship between sarcopenia and sarcopenic obesity and EC. In this study, our aim was to investigate the relationship between the cross‐sectional imaging‐based body composition parameters and the disease prognosis in low‐grade (LG) and high‐grade (HG) EC. Materials and Methods We conducted a retrospective study in women diagnosed with low and high‐grade EC between January 2014 and May 2022 who had abdominal MRI and thorax CT as a part of routine staging workup. We used the skeletal muscle index (SMI) at the level of the third lumbar vertebra to assess sarcopenia on CT. The T2‐weighted sequence at the level of the L2–L3 intervertebral disc is used for visceral fat area (VFA), subcutaneous fat area (SFA), and total fat area (TFA). Two radiologists in consensus, calculated the parameters. Results A total of 250 EC patients (144 low‐grade EC, 106 high‐grade EC).Sarcopenia was observed in 122 (48.8%) patients, and sarcopenic obesity was found in 82 (32.8%) patients. Although there was an increase in VFA in cases with high‐grade EC, there was no significant difference in terms of SFA. Additionally, the frequency of sarcopenia and sarcopenic obesity was higher in cases with high‐grade EC. There was no association between sarcopenia and age, histological type, FIGO staging, or comorbidity in the univariate analysis. However, BMI was found to be associated with sarcopenia. Conclusions Quantitative radiological measurement of sarcopenia, sarcopenic obesity, and body fat composition can be used as novel parameters in the prediction of disease prognosis in endometrial cancer.

ZC3H13‐induced the m6A modification of hsa_circ_0081723 promotes cervical cancer progression via AMPK/p53 pathway

AbstractBackgroundN6‐methyladenosine (m6A) modification and circular RNAs (circRNAs) have been confirmed to participate in cervical cancer (CC) progression. However, the function of a novel circRNA, hsa_circ_0081723, has not yet been explored in CC. Therefore, this study aimed to investigate the potential role of hsa_circ_0081723 and its m6A modification in CC.MethodsThe hsa_circ_0081723 and ZC3H13 expressions were examined by qRT‐PCR in the CC tissues, and their prognostic significance was evaluated via Kaplan–Meier Plotter. The role of hsa_circ_0081723 in CC progression was checked by loss‐of‐function assays. The relative protein levels of AMPK/p53 pathway were determined by western blotting. The interactions of hsa_circ_0081723 and ZC3H13 were verified via MeRIP and RNA stability assays.ResultsThe hsa_circ_0081723 expression was elevated in CC samples, and its higher levels indicated high histological grade, high FIGO stage, poor differentiation, and poor prognosis. Functionally, silencing hsa_circ_0081723 impaired the malignant behavior of CC cells and enhanced the protein levels of key molecules of the AMPK signaling pathway. Moreover, ZC3H13 was also elevated in CC samples and demonstrated a positive association with hsa_circ_0081723. The relative enrichment of hsa_circ_0081723 m6A and its stability were enhanced in ZC3H13 overexpressed CC cells. Mechanically, ZC3H13 overexpression partially reversed the antitumor effects caused by hsa_circ_0081723 knockdown in CC cells.ConclusionsThis study innovatively demonstrates that ZC3H13‐mediated m6A modification of hsa_circ_0081723 promotes CC progression by modulating AMPK/p53 pathway. Our findings may contribute to the understanding of the molecular mechanisms underlying CC and offer potential therapeutic targets for clinical treatment.

MiR‐326 regulates the proliferation and apoptosis of endometrial cancer by targeting Bcl‐2

AbstractAimMiR‐326 has been investigated to be correlated with multiple types of malignancies; however, the role of miR‐326 in endometrial cancer (EC) remains rarely reported. The aim of our research is to investigate the functions of miR‐326 in EC and the potential molecular mechanism.MethodsRT‐qPCR was performed to compare the expression of miR‐326 and Bcl‐2 in normal endometrial epithelial cell line (End1/e6e7) and EC cells lines (HEC‐1A, Ishikawa), respectively. Bioinformatic analysis and luciferase assay verified the relationship between miR‐326 and the 3’‐UTR of Bcl‐2. 3‐(4,5‐dimethyl‐2‐thiazolyl)‐2,5‐diphenyl‐2‐H‐tetrazolium bromide (MTT) assay, soft agar colony formation assay and the flow cytometry were performed to investigate the functions of miR‐326 and Bcl‐2 on proliferation and apoptosis in EC. Western blotting was employed to explore the expression of Bcl‐2, Bcl2‐associated X (Bax) and caspase‐3.ResultsThe expression of miR‐326 decreased in EC cell lines compared to normal endometrial epithelial cell line, while Bcl‐2 expression was increased in EC cells. Results of MTT and soft agar colony formation assays showed that miR‐326 suppressed proliferation in EC cells. In addition, flow cytometry revealed that miR‐326 promoted apoptosis in EC cells. Western blotting showed that silencing miR‐326 promoted the expression of Bcl‐2. Bioinformatics analysis and luciferase assay verified the 3’‐UTR of Bcl‐2 was a target of miR‐326. Furthermore, MTT assay, soft agar colony formation assay and the flow cytometry proved that miR‐326 acts as tumor suppressor via inhibiting the expression of Bcl‐2.ConclusionMiR‐326 acts as a cancer suppressor to inhibit proliferation and promote apoptosis via targeting Bcl‐2 axis in EC.

Clinical pathological characteristics and survival of high‐grade endometrioid carcinoma

AbstractObjectiveThe molecular features of high‐grade endometrioid carcinoma (HGEC) are more akin to nonendometrioid high‐grade carcinoma (NEHC). This study aims to explore whether HGEC also has similar clinical pathology and prognosis similar to NEHC.MethodsUsing the SEER database (Surveillance, Epidemiology, and End Results), a retrospective study of the clinical‐pathological data and prognosis was carried out.Result(1) Compared with LGEC (low‐grade endometrioid carcinoma), HGEC patients were older with larger tumor size and a higher proportion of stage III–IV disease. However, the young had a lower proportion of stage III–IV disease than NEHC. (2) Postoperative pathological examination revealed that the positive rate of peritoneal cytology, pelvic lymph nodes and para‐aortic lymph nodes in HGEC were significantly higher than LGEC, but lower than NEHC. LGEC, HGEC, and NEHC, all showed distant organ metastases such as brain metastases, bone metastases, liver metastases, and lung metastases. Notably, the metastasis rates between HGEC and NEHC were not significantly different but were higher than LGEC. (3) The five‐overall survival rates of LGEC, HGEC, and NEHC were 95.1%, 73.2%, and 54.8%, respectively. Notably, the survival rates decreased significantly in stage IV. There were no significant differences between HGEC and NEHC in stage IV (p = 0.665) and both were associated with worsened survival. Also, HGEC survival prognosis was similar to NEHC.ConclusionHGEC presents mixed or overlapping clinical–pathological features of NEHC. Therefore, based on the unique pathological and prognostic features, HGEC could be classified as an intermediate between LGEC and NEHC.

Combination therapy with paclitaxel and trastuzumab for human epidermal growth factor receptor 2‐positive recurrent serous carcinoma of the uterine cervix: A case report

Abstract Recent studies show increased expression of human epidermal growth factor receptor 2 (HER2) in cervical cancer, but the efficacy of anti‐HER2 therapy remains under‐researched. Here, we present a case of recurrent HER2‐positive serous carcinoma, presumably arising in the cervix, diagnosed by comprehensive genomic profiling, which responded to trastuzumab. The patient underwent a radical hysterectomy with concurrent adjuvant chemoradiotherapy. One year after surgery, the patient experienced recurrence (multiple lymph node metastases). She underwent chemotherapy and subsequent comprehensive genomic profiling, which revealed HER2 positivity. Despite treatment, the lymph node and peritoneal metastases progressed. Therefore, combination chemotherapy with paclitaxel and trastuzumab was initiated. Subsequently, the patient's clinical symptoms improved considerably, and good health was maintained for 8 months. This report highlights the importance of comprehensive genomic profiling and targeted therapies when standard treatments fail.

Perivascular Epithelioid Cell Neoplasm of the Uterus: A Case Report

ABSTRACT Perivascular epithelioid cell neoplasms (PEComas) represent a rare category of mesenchymal tumors, with the gastrointestinal and gynecological systems being the most frequently affected sites. A 46‐year‐old patient was referred to our clinic due to prolonged menstrual bleeding, without additional symptoms. Histopathological analysis of the specimens collected through exploratory curettage demonstrated the presence of uterine PEComa, characterized by positive immunohistochemical markers including HMB‐45, TFE3, Cathepsin K, and ER. The patient underwent laparoscopic hysterectomy with bilateral adnexectomy. No recurrence of the disease was observed during the subsequent examinations. This case underscores a common diagnostic pitfall: the absence of a distinct mass on imaging. It highlights that a PEComa can present with only non‐specific endometrial thickening, making preoperative diagnosis exceptionally challenging and reliant on histopathology. Laparoscopic surgery in our case provided the patient with quick recovery and a less invasive approach with satisfying results and the absence of recurrent disease during a one‐year follow‐up period. Future multicenter studies should facilitate a deeper comprehension and undoubtedly lead to a more effective management of a rare and enigmatic condition that is uterine PEComa.

lncRNA RHPN1‐AS1 promotes the progression of endometrial cancer through the activation of ERK/MAPK pathway

AbstractAimThis study aimed to investigate the function of long noncoding RNA RHPN1 antisense RNA 1 (lncRNA RHPN1‐AS1) in the progression of endometrial cancer (EC) and its underlying molecular mechanisms.MethodsThe RHPN1‐AS1 expression was measured by quantitative reverse transcriptase‐polymerase chain reaction (qRT‐PCR) in EC tissues and cells. The cell clones, proliferation, cell cycle, apoptosis, migration and invasion in Ishikawa and HEC‐1A cells were respectively measured by colony formation assay, cell counting kit‐8 assay (CCK‐8) assay, flow cytometry, wound healing assay and transwell assay. In addition, the protein expressions in Ishikawa and HEC‐1A cells were measured using western blot and Immunofluorescence assay.ResultsOur data showed the RHPN1‐AS1 expression was significantly upregulated in both EC tissues and cells. The expression of RHPN1‐AS1 was significantly correlated with FIGO stage, histological grade, and lymph node metastasis. Additionally, silencing RHPN1‐AS1 could inhibit proliferation, cell cycle progression, migration and invasion, and also promote apoptosis in Ishikawa and HEC‐1A cells. Moreover, silencing RHPN1‐AS1 could markedly elevate the expressions of caspase‐3 and Bax, but reduce the Bcl‐2 expression in Ishikawa and HEC‐1A cells. We also found that silencing RHPN1‐AS1 could significantly inhibit the phosphorylation of MEK and ERK in Ishikawa and HEC‐1A cells. After U0126 pretreatment, the inhibition effect of silencing RHPN1‐AS1 on the phosphorylation of MEK and ERK was strengthened.ConclusionOur study demonstrated that RHPN1‐AS1 could facilitate cell proliferation, migration and invasion, as well as inhibit apoptosis via activating ERK/MAPK pathway in EC.

Validation of the 2023 FIGO staging system and its concordance with the JSGO guidelines in endometrial cancer: A multi‐institutional retrospective study in Japan

Abstract Aim To validate the prognostic accuracy of the 2023 FIGO staging system and assess its alignment with the Japan Society of Gynecologic Oncology (JSGO) guidelines for endometrial cancer treatment. Methods This retrospective cohort study included 1207 patients with endometrial cancer treated at four academic hospitals in Kanagawa, Japan, between 2018 and 2022. Patients were reclassified according to the FIGO 2023 system and the JSGO recurrence risk categories. Primary endpoints included stage migration, recurrence risk (RR), overall survival (OS), and concordance between the two classification systems. Results Under FIGO 2023, the stage distribution was: I, 741 (61.4%); II, 203 (16.8%); III, 149 (12.3%); and IV, 114 (9.4%), with stage migration observed in 36.3% of cases. The FIGO 2023 system provided clearer stratification of 3‐year RR than FIGO 2009, with the RR gap widening from 80.0% to 90.1%. Sixteen patients (3.5%) with stage IA3 were classified as high risk by JSGO criteria, while 14.4% of patients considered high risk by JSGO were downstaged under FIGO 2023. Additionally, 46 patients (19.6%) with FIGO stage IA were reclassified as intermediate risk owing to focal lymphovascular space invasion (LVSI). Substantial LVSI was significantly associated with recurrence and poor prognosis (3‐year OS rates: none 94.3%, focal 89.9%, and substantial 40.7%; p  < 0.05). Molecular testing was limited: p53 in 30.2%, MSI in 5.9%, and POLE was not available. Conclusions FIGO 2023 improves prognostic precision. Incorporating LVSI extent and molecular data may refine JSGO classifications and support more individualized adjuvant therapy strategies.

A retrospective observational study of changes in uterine fibroid blood flow and fibroid diameter after administration of gonadotropin‐releasing hormone agonists and antagonists using superb microvascular imaging

Abstract Aim The relationship between the changes in fibroid blood flow and fibroid diameter during the administration of GnRH agonists and antagonists was examined using superb microvascular imaging (SMI). Methods Changes in the maximum fibroid blood flow and diameter at weeks 0, 2, 4, and 8 were compared between the relugolix, a GnRH antagonist, and leuprolide, a GnRH agonist, groups. Results Data were collected for 16 fibroids from 12 patients in the relugolix group and 12 fibroids from 9 patients in the leuprorelin group. A significant decrease was observed in the fibroid diameter at 8 weeks in the relugolix group, but no significant change was observed at any time point in the leuprorelin group. In the relugolix group, a significant correlation were observed between changes in blood flow at 2 weeks and fibroid diameter changes at 2 and 4 weeks, and between changes in blood flow at 4 weeks and fibroid diameter changes at 4 weeks. No significant correlation was observed in the leuprorelin group. Conclusion In the treatment of uterine fibroids with relugolix, a reduction in fibroid blood flow assessed by SMI may suggest a subsequent reduction in fibroid size. These results provide useful insights when making the decision whether or not to continue relugolix administration.

The role of serum inflammatory markers in determining the severity of cervical lesions

AbstractObjectiveTo evaluate the role of serum inflammatory markers in determining colposcopy indications more accurately, reducing unnecessary colposcopy requests, and preventing overtreatment.Materials and MethodsIn our study, the data of 218 patients who were followed up in our hospital's oncology outpatient clinic between April 2017 and November 2023 and who underwent colposcopy and biopsy for suspected cervical lesions due to Papanicolaou smear test abnormalities or the presence of human papillomavirus were evaluated retrospectively. The parameters of patients with and without cervical lesions were compared. Patients with cervical lesions were compared according to lesion type.ResultsNeutrophil/lymphocyte ratio and platelet/lymphocyte ratio levels were significantly higher in the cervical lesions (+) group compared with the cervical lesions (−) (p < 0.001 and p < 0.001, respectively). Systemic immuno‐inflammation index and systemic inflammatory response index levels were significantly higher in the cervical lesions (+) group compared with the cervical lesions (−) group (p < 0.001 and p < 0.001, respectively). Mean platelet volume level was significantly lower in the cervical lesions (+) group compared with the cervical lesions (−) group (p < 0.001). In the group with cervical lesions, no significant relationship was found between the severity of the cervical lesions and serum inflammatory marker levels.ConclusionAccording to the results of our study, although there were significant differences between the serum inflammatory marker levels of patients with and without cervical lesions, their importance in predicting cervical lesions could not be clearly demonstrated. The importance of serum inflammatory markers should be evaluated in prospective studies with larger patient numbers and longer follow‐up periods.

Awareness and attitude toward cardio‐oncology among Japanese gynecologic oncologists in managing patients with endometrial cancer: The Japanese Gynecologic Oncology Group (JGOG) questionnaire surveys

AbstractAimThis study aimed to assess the awareness of the concept of “cardio‐oncology” and cardiovascular disease (CVD) in patients with endometrial cancer (EC) among the Japanese Gynecologic Oncology Group members.MethodsAn online anonymous survey, which consisted of questions about respondent attributes and cardio‐oncology, was conducted twice, in 2022 and 2024. During these surveys, guidelines for the treatment of uterine body neoplasm were published in July 2023.ResultsIn 2022, significantly numerous physicians were unaware of cardio‐oncology or the increased risk of developing CVD in patients with EC, and 25.3% of them answered that they had no idea about cardio‐oncology at all. However, in 2024, the percentage significantly dropped to 8.7%. The number of physicians who were aware that CVD is more common as the cause of death in patients with low‐grade EC than the cancer itself was significantly higher in 2024 than in 2022. Similarly, the number of physicians who were aware that the usage of platinum agents could become a risk factor for CVD was significantly higher in 2024. Furthermore, this study reported challenges in the collaboration between oncologists and primary care physicians in the region and in the provision of guidance for preventing metabolic syndrome.ConclusionJapanese Gynecologic Oncology Group members' awareness of cardio‐oncology was inadequate, but it seemed to be improving, especially after publishing the guideline for the treatment of uterine body neoplasm. Thus, raising awareness of cardio‐oncology and managing CVD risk in patients with EC are necessary to improve long‐term survival after cancer diagnosis.

Clinical outcomes after 2‐year follow‐up of transvaginal radiofrequency ablation of symptomatic uterine fibroids

AbstractAimThe aim of this study was to evaluate the efficacy after 2 years follow‐up of transvaginal radiofrequency ablation (TVRA) to treat myomas, and to identify factors predictive of the response to the treatment.MethodsThis is a prospective cohort study of a 2‐year follow‐up of 65 patients who underwent TVRA for the treatment uterine fibroids at Virgen de las Nieves University Hospital in Granada, Spain. Ultrasound mean fibroid volume, symptom severity scale, total bleeding days, complications, pregnancy outcomes were recorded.ResultsStatistically significant improvements in symptoms and bleeding were observed at 6, 12, and 24 months after the procedure. The mean myoma volume (cc) was significantly lower (p < 0.05) at 12 and 24 months, with a mean reduction in myoma volume of more than 80% and 60%, respectively. After a 24‐month follow‐up, 5 patients (7.7%) required additional surgical treatment to control symptoms. Patient age (>40 years), initial myoma size, and the timing of radiofrequency were identified as factors related to outcomes in the bivariate analysis.ConclusionsTransvaginal radiofrequency ablation is an effective and safe technique for the treatment of myomas after 2 years of follow‐up, which improves the symptoms of the patients and decreases the final volume of the myoma.

Are all vulvar masses Bartholin cysts? A series of cases

AbstractIntroductionWhile vulvar masses are not prevalent in society, they are one of the reasons for complaints that arise during visits to gynecology outpatient clinics. An excision is typically necessary for both the purpose of diagnosing and treating the condition.MethodsWe documented three exceptional instances with distinct histopathological diagnoses and varying presentations, as well as a consecutive series of five patients, including one Bartholin abscess and one labia major abscess.ResultsDuring the compilation of this article, we intended to show that vulvar masses can manifest in various forms. It is important not to overlook pathologies other than Bartholin cysts and abscesses, which are commonly encountered reasons for admission to gynecology clinics. Additionally, it is crucial to always consider the possibility of malignant pathologies.DiscussionClinicians' expertise and understanding of vulvar masses are comparatively inferior to their knowledge of other gynecological disorders. This case series presents the uncommon vulva masses that we found in our clinic.

Comparison of laparoscopy and vNOTES in early‐stage endometrial cancer

Abstract Aim To compare the demographic, clinical, surgical, histopathological, and oncological outcomes of vNOTES and conventional laparoscopy (CL)for early‐stage endometrial cancer. Methods A retrospective study was carried out in the Gynecologic Clinic of a tertiary hospital from January 2019 to November 2020. Patient demographic characteristics, surgical outcomes, histopathological characteristics, visual analog scale (VAS) pain scores at postoperative 6th, 12th, and 24th, intra‐ and postoperative complications, and follow‐up results were noted. Results A total of 45 patients enrolled, of which 16 underwent CL and 29 were vNOTES. The operative time and decrease in hemoglobin levels were similar for both groups ( p  = 0.202, p  = 0.699). Postoperative hospital stay did not differ between the vNOTES group and the CL group ( p  = 0.549). VAS pain scores at postoperative 6th, 12th, and 24th h were significantly lower in vNOTES group than in the CL group ( p  < 0.001). The requirement for additional opioid/narcotic analgesic was lower in the vNOTES group than in the CL group ( p  = 0.037). Conclusion vNOTES may be a safe and feasible option in early‐stage endometrial cancer, having less postoperative pain and less requirement of opioid/narcotic analgesic compared with laparoscopy.

A single institutional clinical outcome for stages III and IV ovarian cancer patients treated with dose‐dense TC therapy in the frontline or first platinum‐sensitive relapse setting

Abstract Aim Dose‐dense paclitaxel /carboplatin (ddTC) therapy was shown to be more effective against ovarian cancer than conventional tri‐weekly TC in the JGOG3016 study. However, two phase III studies performed after JGOG3016 did not show the same positive results. Because we have been using ddTC in the frontline or first platinum‐sensitive relapse of ovarian cancer, we investigated the clinical outcome of the patients treated with ddTC. Methods We retrospectively examined the response rate (RR), progression free survival (PFS) and adverse events of the patients who were treated with ddTC for stage III and IV epithelial ovarian, tubal and peritoneal cancer from January 2012 to December 2018. Results We analyzed 50 patients for frontline treatment and 11 patients for first platinum‐sensitive relapse treatment, excluding those receiving maintenance therapy. Among the patients that received frontline ddTC treatment, RR was 82.9% for those in a neo‐adjuvant chemotherapy (NACT) setting and 85.0% for those in an adjuvant setting. The median progression‐free survival (PFS) was 20 months after initial therapy. Among 31 cases that achieved remission by frontline surgery and the following ddTC, 22 had a platinum‐sensitive relapse. RR of 11 patients treated with ddTC therapy alone for the first platinum‐sensitive relapse was 81.8%, and the median PFS of these patients was 22 months after the first recurrence. Conclusions ddTC therapy for advanced ovarian cancer achieved high response rates in all settings (NACT, adjuvant or platinum‐sensitive relapse). ddTC therapy was effective for improving the prognosis of patients with stages III and IV of ovarian cancer.

Olaparib maintenance therapy for platinum‐sensitive relapsed ovarian cancer at a single institution: A retrospective study

Abstract Aim In this study, we aimed to investigate patient characteristics, efficacy, prognostic factors, and safety of olaparib maintenance therapy for platinum‐sensitive recurrent ovarian cancer at our institution. Methods Patients responding to platinum‐based therapy and starting olaparib maintenance therapy for recurrent epithelial ovarian, fallopian tube, or peritoneal cancer at Kurume University Hospital between January 2018 and November 2021 were enrolled in the study. Their data were extracted retrospectively from medical records. Results In all, 50 patients were included. The median (range) age of the patients, follow‐up time, and duration of olaparib maintenance therapy were 62 (39–87) years, 21.6 (2.2–45.9) months, and 7.2 (2–45.9) months, respectively. Among the 29 patients tested for homologous recombination (HR) status, 22 (75.9%) were positive for HR deficiency (HRD), 12 (54.5%) of whom had BRCA ‐positive tumors. The median progression‐free survival was 8.9 months (95% confidence interval: 6.2–12.6), and the median overall survival was 27.1 months (95% confidence interval: 22.5–40.3). Multivariate analysis of prognostic factors revealed that HRD was an independent prognostic factor for both progression‐free survival and overall survival. The most common adverse event was nausea (any grade, n  = 30, 60%), resulting in drug interruption ( n  = 23, 46%), dose reduction ( n  = 17, 34%), and discontinuation of treatment ( n  = 1, 2%). Conclusion Olaparib maintenance therapy for recurrent platinum‐sensitive ovarian cancer at our institution was effective, with acceptable adverse events. HRD was the most significant prognostic factor for patients with recurrent platinum‐sensitive ovarian cancer.

Defining the relationship between ovarian adult granulosa cell tumors and synchronous endometrial pathology: Does ovarian tumor size correlate with endometrial cancer?

Abstract Objective The main feature of adult granulosa cell tumors (AGCT) is their capacity to secrete hormones, with nearly all of them capable of synthesizing oestradiol. The primary goal of this study is to identify synchronized endometrial pathologies, particularly endometrial cancer, in AGCT patients who had undergone a hysterectomy. Materials and Methods The study cohort comprised retrospectively of 316 AGCT patients from 10 tertiary gynecological oncology centers. AGCT surgery consisted of bilateral salpingo‐oophorectomy, hysterectomy, peritoneal cytology, omentectomy, and the excision of any suspicious lesion. The median tumor size value was used to define the relationship between tumor size and endometrial cancer. The relationship between each value and endometrial cancer was evaluated. Results Endometrial intraepithelial neoplasia, or hyperplasia with complex atypia, was detected in 7.3% of patients, and endometrial cancer in 3.1% of patients. Age, menopausal status, tumor size, International Federation of Gynecology and Obstetrics stage, ascites, and CA‐125 level were not statistically significant factors to predict endometrial cancer. There was no endometrial cancer under the age of 40, and 97.8% of women diagnosed with endometrial hyperplasia were over the age of 40. During the menopausal period, the endometrial cancer risk was 4.5%. Developing endometrial cancer increased to 12.1% from 3.2% when the size of the tumor was >150 mm in menopausal patients ( p  = 0.036). Conclusion Endometrial hyperplasia, or cancer, occurs in approximately 30% of AGCT patients. Patients diagnosed with AGCT, especially those older than 40 years, should be evaluated for endometrial pathologies. There may be a relationship between tumor size and endometrial cancer, especially in menopausal patients.

Dose reduction of olaparib in older patients: Insights from an analysis of a National Database in Japan

AbstractAimAlthough the advent of a poly polymerase inhibitors has greatly advanced the tailoring of cancer treatment, there is a dearth of real‐world evidence on the actual use of olaparib in aging populations, especially those using national‐level data.MethodsWe extracted and analyzed all prescriptions of olaparib in female outpatients from the National Database Open Data Japan (NDB Open Data) from April 2019 to March 2021. The recommended standard dose of olaparib is four tablets of the 150 mg formulation per day, while the 100 mg formulation of olaparib can be considered as an alternative dose in the occurrence of hematologic toxicity. We calculated the proportion of 100 mg compared to the 150 mg prescriptions across age groups. A Cochrane–Armitage trend test was used to examine the association of age groups with the proportion of 100 mg prescriptions.ResultsThe total number of prescriptions of the 100 mg formulation and the 150 mg formulation were 1449 222, and 4233 625, respectively. Overall, 45.1% (2567 513/5682 847 prescriptions) of olaparib were prescribed for patients 65 years of age or older in females. Stratified by age group, the proportion of 100 mg compared to the 150 mg prescriptions significantly increased with age (p < 0.0001).ConclusionsGiven that the 100 mg formulation of olaparib can be considered as an alternative dose in Japan in the occurrence of hematologic toxicity, our observations indicate the dose reduction of olaparib in older patients in Japan. Further investigations are necessary to assess its efficacy and safety at a reduced dose.

BRCA1 expression, its correlation with clinicopathological features, and response to neoadjuvant chemotherapy in high‐grade serous ovarian cancer

AbstractAimIn high‐grade serous ovarian cancers (HG‐SOC), BRCA1 mutation is one of the predominant mutations reported by various studies. However, the non‐mutational mechanisms of BRCA pathway inactivation in HG‐SOC are unclear. We evaluated BRCA1 inactivation by estimating its expression with its repressor, ID4, in primary and neoadjuvant chemotherapy (NACT)‐treated HG‐SOC tumors with known therapeutic responses.MethodsWe evaluated the expression pattern of BRCA1 protein by immunohistochemistry in 119 cases of HG‐SOC from a hospital cohort consisting of primary (N = 69) and NACT‐treated (N = 50) tumors. Histological patterns (SET), stromal infiltration by lymphocytes (sTILs), and chemotherapy response score (CRS) were estimated by microscopic examination. Gene expression levels of BRCA1, and its repressor ID4, were estimated by qPCR. The association of BRCA1 protein and mRNA with clinicopathological features was studied. The relevance of the BRCA1/ID4 ratio was evaluated in tumors with different CRS.ResultsBRCA1 protein expression was observed in 12% of primary and 19% of NACT‐treated HG‐SOC tumors. We observed moderate concordance between BRCA1 protein and mRNA expression (AUC = 0.677). High BRCA1 mRNA expression was significantly associated with a more frequent SET pattern (p = 0.024), higher sTILs density (p = 0.042), and increased mitosis (p = 0.028). BRCA1‐negative tumors showed higher expression of ID4 though not statistically significant. A higher BRCA1/ID4 ratio was associated with high sTILs density in primary (p = 0.042) and NACT‐treated tumors (p = 0.040).ConclusionOur findings show the utility of the BRCA1/ID4 ratio in predicting neoadjuvant therapy response, which needs further evaluation in larger cohorts with long‐term outcomes.

Endometrial polyps effect on pregnancy outcomes in infertile women with minimal/mild endometriosis: A retrospective study

AbstractObjectiveTo assess the pregnancy outcomes and associated influencing factors of pregnancy after hysteroscopy combined with laparoscopy treatment in infertile patients with minimal/mild endometriosis.DesignA retrospective study.SettingWest China Second University Hospital of Sichuan University.PatientsWe enrolled 898 infertile women who had their minimal/mild endometriosis lesions removed by laparoscopy, including 271 patients additionally diagnosed with endometrial polyps who also underwent hysteroscopic polypectomy.MethodsBased on the existence of endometrial polyps, patients with minimal/mild endometriosis were enrolled and divided into polyps group and non‐polyps group.Main Outcome MeasuresPregnancy outcomes.ResultsA total of 271 women with minimal/mild endometriosis were included in polyps group while 491 women with minimal/mild endometriosis were included in non‐polyps group. The pregnancy rate of polyps group was not statistically significant compared with non‐polyp group (60.15% vs. 58.25%). The pregnancy rate was higher among patients with polyps ≥1 cm (76.06%, 54/71) than patients with polyps <1 cm (54.50%, 109/200) or patients without polyps (58.25%, 286/491) (p = 0.006). The pregnancy rate was higher for patients with multiple polyps (67.86%, 95/140) than for patients with single polyp (51.91%, 68/131) or without polyps (p = 0.025).ConclusionsAmong women with minimal/mild endometriosis, hysteroscopic polypectomy did significantly increase fertility in infertile patients with multiple polyps or size of polyp ≥1 cm compared with those without endometrial polyps, single polyp, and size of polyp <1 cm. The size and number of polyps were independently associated with the reproductive ability of women with minimal/mild endometriosis.

FIGO Session

Thiol‐disulfide status of patients with cervical cancer

AbstractAimThe evaluation of dynamic thiol‐disulfide homeostasis among patients with the cancer of the uterine cervix.MethodsThe study was conducted in 62 cervical cancer patients and 61 healthy women who had been followed up in an obstetrics and gynecology clinic between September 2018 and April 2020. Serum disulfide, native thiol, total thiol, ischemia modified‐albumin, total antioxidant and oxidant capacities, and oxidative stress index values were measured in all participants.ResultsThe mean plasma disulfide levels of the cervical cancer group was statistically significantly higher than that of the control group (25.79 ± 6.90 μmol/L, 22.31 ± 6.11 μmol/L, respectively) (P = 0.004). Plasma native thiol and total thiol levels were lower in cervical cancer patients (299.27 ± 99.05 μmol/L and 350.86 ± 102.72 μmol/L, respectively) compared to controls, but no statistically significant difference was observed (318.00 ± 93.75 μmol/L and 376.44 ± 98.51 μmol/L, respectively) (P = 0.284, P = 0.161). With respect to the ischemia modified‐albumin level, no statistically significant difference was observed between two groups. There were statistically significant positive association between disulfide level and both the stage of cervical cancer (r = 0.278, P = 0.029) and total oxidant capacity level (r = 0.256, P = 0.046).ConclusionDynamic thiol‐disulfide homeostasis may participate in the pathophysiological mechanisms of cervical cancer and may be a potential biomarker for early identification of cervical cancer in future.

Temporal changes in magnetic resonance imaging appearance of adult granulosa cell tumor

AbstractGranulosa cell tumors (GCTs) can have a wide variety of appearances on magnetic resonance imaging (MRI), ranging from entirely solid to multilocular cystic, suggesting that GCTs undergo remarkable morphological changes during growth. These temporal changes in MRI appearance of individual GCTs have not been documented. A 54‐year‐old asymptomatic postmenopausal woman was referred to our department for a small ovarian mass. This 3‐cm solid mass showed high intensity on diffusion‐weighted MRI and low intensity on apparent diffusion coefficient mapping. Close clinical follow‐up was recommended, but she did not return to our hospital until the age of 63, when she was referred for a large ovarian tumor. MRI showed a 15‐cm multilocular cyst containing a solid component with hemorrhaging. Postoperative diagnosis was adult GCT (AGCT). These temporal changes demonstrate a possible reason why GCTs can have such a wide range of MRI appearance. This knowledge might promote accurate preoperative diagnosis of AGCTs.

The efficacy of anti‐angiogenic drugs in gastric‐type endocervical adenocarcinoma: A retrospective study

AbstractObjectivesGastric‐type endocervical adenocarcinoma (GEA) is a rare malignant tumor that is not associated with high‐risk HPV infection, known for its high invasiveness and resistance to current treatments. This study assessed the effectiveness of anti‐angiogenic regimens in real‐world GEA patients.MethodsPatients with GEA were enrolled between February 2012 and March 2023, and their clinicopathological characteristics were collected from their medical records. The patients were categorized into groups based on whether they received anti‐angiogenic treatments or not. Survival analysis was conducted using the Kaplan–Meier method.ResultsA total of 43 GEA patients were enrolled in this study, with 23 cases who received anti‐angiogenic drugs (nine received them as the primary treatment, 12 as first‐line therapy after recurrence/metastasis, and two as second‐line therapy) as the observation group. The other 20 patients who received similar treatments without the anti‐angiogenic regimens serve as the control group. Compared to the control group, the addition of anti‐angiogenic drugs as the primary treatment mildly extended progression‐free survival (PFS) while not being statistically significant (16 months vs 11 months, p = 0.744). The negative results were also observed in 12 patients who started anti‐angiogenic therapy as first‐line therapy after recurrence/metastasis (8.5 months vs 9 months, p = 0.518). As for the overall survival (OS), no benefits were detected in either patients who started the anti‐angiogenic therapy as primary or subsequent treatments (p = 0.499 and 0.450, respectively).ConclusionWe firstly evaluated the efficacy of anti‐angiogenic drugs in treating patients with GEA. Although with a small sample size, our preliminary results clearly proposed that the anti‐angiogenic therapy failed in suppressing tumors and should not be a preferred choice for GEA. As a much rarer tumor without standard treatments, we herein warned of a pitfall for gynecologic oncologists when facing this malignancy.

Tumor diameter as a predictor of lymph node involvement in endometrioid type endometrial adenocarcinomas

AbstractAimTo analyze the risk factors of lymph node involvement in pure endometrioid type endometrial cancer and assess factors that necessitate lymphadenectomy.MethodsPatients who had been operated on due to endometrial cancer and whose final pathology was reported as pure endometrioid carcinoma between January 2014 and January 2020 were assessed. Hysterectomy, bilateral salpingo‐oophorectomy, and systematic lymphadenectomy were performed in all patients. All specimens were reported by expert gynecopathologists.ResultsThe lymph node positivity rate was 14.4%. When the study population was classified according to the Mayo risk criteria; lymph node involvement in the low‐risk and high‐risk groups was 9.1% and 14.8%, respectively and there was no statistically difference (p > 0.05). The median of tumor size and the rate of deep myometrial invasion, lymphovascular space invasion, adnexal involvement, FIGO grade 3 tumor were found significantly higher in the positive lymph node group in univariate analysis. In the receiver operating characteristic curve analysis, the cut‐off value of the tumor diameter was determined as 47.5 mm (sensitivity 85%, specificity 62%). Every 10 mm increase in tumor diameter increased the risk of lymph node involvement 10 times.ConclusionThis study defined that the tumor diameter is an independent predictor for lymphatic dissemination. In the future, it could be shown that even with new modeling based on tumor diameter, lymphadenectomy or adjuvant radiotherapy requirements would be reevaluated.

Survival and reproductive outcomes after fertility‐sparing surgery performed for borderline epithelial ovarian tumor in Japanese adolescents and young adults: Results of a retrospective nationwide study

AbstractObjectiveEpithelial borderline ovarian tumor (BOT) frequently occurs in young women. Because progression‐free survival, overall survival, and reproductive function are important outcomes, BOT is often treated by fertility‐sparing surgery (FSS). We conducted a Japan‐wide study to understand post‐FSS prognosis in relation to clinical characteristics and types of FSS performed.MethodsWe analyzed clinical and outcome data pertaining to 531 adolescent and young adult (AYA) patients (aged 15–39 years) who underwent FSS for BOT between 2009 and 2013.ResultsMedian (range) age was 30 (15–39) years, and median observation time was 70 (2–120) months. The disease was of FIGO stage I in 492 (93%) patients. Histopathologically, tumors were of the mucinous (n = 372, 70%), serous (n = 120, 23%), seromucinous (n = 23, 4%), and other (n = 16, 3%) types. Five‐year overall survival was 99.5% among patients with stage I and 100% among those with stage II–IV. Five‐year progression‐free survival was 96.7% and 69.3%, respectively. Multivariate analysis in cases of stage I showed a positive peritoneal cytology to be a significant risk factor for recurrence (HR, 5.199; p = 0.0188). The post‐FSS pregnancy rate was relatively low for patients aged ≥30 years (OR, 0.868; 95% CI, 1.16–3.00; p = 0.0090).ConclusionPost‐FFS outcomes in terms of overall and progression‐free survival are favorable, especially for AYA patients with stage I BOT. However, the relapse rate is high for patients with FIGO stage II–IV and for those with stage I but a positive peritoneal cytology. A long‐term prospective observation is needed before reproductive outcomes can be fully established.

Extremely high anti‐Mullerian hormone levels detected during infertility workup revealing sex cord tumor with annular tubules and underlying Peutz–Jeghers syndrome: A case report

AbstractWe report an infertile, but otherwise asymptomatic woman, whose extremely high anti‐Mullerian hormone (AMH) level detected during infertility investigation led to the diagnosis of sex cord tumor with annular tubules (SCTAT) which is a very rare sex cord‐stromal tumor (SCST) and eventually revealed a previously undiagnosed hereditary cancer syndrome, Peutz–Jeghers syndrome (PJS). A 33‐year‐old woman attended Kocaeli University ART Clinic for infertility evaluation. Her AMH level was 319.63 ng/ml. Detection of bilateral ovarian cysts required surgical evaluation. The histopathological examination of ovaries revealed SCTAT. The strong association of SCTAT with PJS raised the suspicion of this syndrome. Whole STK11 gene sequencing confirmed PJS diagnosis. AMH has become a widely used tool in the evaluation of infertile women. Clinicians dealing with infertility should be familiar with the utility of AMH measurement besides being a marker of ovarian reserve. Detection of high AMH concentrations should raise the suspicion of an SCST.

Chemotherapy for ovarian cancer during pregnancy: A systematic review and meta‐analysis of case reports and series

AbstractAimThis study aims to investigate the safety and efficacy of chemotherapy in ovarian cancer patients in pregnancy.MethodsIn this study, eligible studies were searched on PubMed, Embase, and Cochrane Library databases up to December 31, 2020. Data were calculated and presented by frequency and percentage, mean ± standard deviation (SD), and median (range), respectively. Kaplan–Meier survival analysis was performed to estimate overall survival (OS) and progression‐free survival (PFS).ResultsFinally, 34 studies including 40 ovarian cancer cases receiving chemotherapy during pregnancy were included. All 40 patients received chemotherapy during pregnancy. During the follow‐up, seven of 37 (18.9%) women had a relapse and four of them (4/7, 57.1%) died of recurrence. Survival analysis failed to reach median OS and PFS within the follow‐up (range 3–72 months). Better OS and PFS after chemotherapy in pregnancy were obtained in women with early‐stage ovarian cancer (I) compared with those with advanced stage (III–IV). Neither OS nor FS differed between women treated with multi‐drugs and those with monotherapy. Forty‐one newborns were delivered from 40 pregnant women. Thirty‐four (34/41, 82.9%) were completely healthy at birth and the end of follow‐up (range 0.18–160 months). However, one newborn died 5 days after birth due to multiple congenital malformations, and another one developed Tourette's syndrome, aphasia, Asperger's syndrome as well as speech delay.ConclusionsThis meta‐analysis first reveals the efficacy and safety of chemotherapy for ovarian cancer during pregnancy, especially for early‐stage patients. Cisplatin or carboplatin is suggested to be used as monotherapy to reduce adverse effects.

Ovarian mass combined with pancreatic neoplasm in pregnancy: A rare case report and literature review

AbstractA 35‐year‐old woman presented with abdominal discomfort at 26 weeks gestation. The magnetic resonance imaging demonstrated a huge unilocular cystic mass with mural nodules originated from body and tail of pancreas. There was also a cystic mass in the left ovary with suppressed intensity on fat saturated image. One week later, she complained of worsening left lower abdominal pain and dyspnea as a new symptom. Hence, distal pancreatectomy with splenectomy and left ovarian cystectomy were performed. The huge cystic mass of pancreas was compressing the diaphragm, and left tubo‐ovarian torsion was observed. This is the second case wherein an MCN of the pancreas with mature cystic teratoma of the ovary caused different symptoms. The management of MCNs in pregnant women should consider multiple aspects such as the malignancy potential of imaging findings, severity of symptoms, and fetal well‐being.

Toward an understanding of tissue factor pathway inhibitor‐2 as a novel serodiagnostic marker for clear cell carcinoma of the ovary

AbstractAimsTissue factor pathway inhibitor (TFPI)‐2 has recently emerged as a serodiagnostic marker for patients with epithelial ovarian cancer (EOC), especially clear cell carcinoma (CCC). This review discusses the biological properties of TFPI‐2 and why serum levels are elevated in CCC patients.MethodsA comprehensive literature search was conducted in PubMed up until March, 2021.ResultsTFPI‐2 is a Kunitz‐type protease inhibitor and negatively regulates the enzymatic activities, such as plasmin. TFPI‐2 has been characterized as a tumor suppressor gene and was frequently downregulated through promoter hypermethylation in various human cancers. In contrast, TFPI‐2 was overexpressed only in CCC. TFPI‐2 may be involved in the pathophysiology of CCC, possibly through regulation of coagulation system, stabilization of extracellular matrix (ECM), and induction of intracellular signal transduction. TFPI‐2 suppresses tissue factor‐induced hypercoagulation in a hypoxic environment. TFPI‐2, secreted by CCC cells, platelets, and adjacent vascular endothelial cells, may suppress tumor growth and invasion through ECM remodeling. Nuclear TFPI‐2 may suppress matrix metalloproteinase production via transcription factors and modulate caspase‐mediated cell apoptosis. CCC cells may upregulate the TFPI‐2 expression to adapt to survival in the demanding environment. TFPI‐2 is secreted by CCC cells and enters the systemic circulation, resulting in elevated blood levels.DiscussionSerum TFPI‐2 reflects the overexpression of TFPI‐2 in CCC tissues and is a potential serodiagnostic marker. Further research is needed to explore the expression, clinical significance, biological function, and potential mechanism of TFPI‐2 in CCC.

Precision medicine for hereditary tumors in gynecologic malignancies

AbstractGenomic medicine for gynecologic tumors is characterized by hereditary breast and ovarian cancer (HBOC) and Lynch syndrome (LS). Poly ADP‐ribose polymerase (PARP) inhibitor, olaparib, and the immune checkpoint inhibitor, pembrolizumab, which are drugs that show sensitivity to each hereditary tumor, have begun to spread in clinical practice for gynecologic malignancies. In clinical use, platinum sensitivity is used as a clinical surrogate marker for olaparib sensitivity, and microsatellite instability is used as a biological surrogate marker for pembrolizumab sensitivity. BRCA genetic testing and microsatellite instability test have been used as companion diagnostics before starting olaparib and pembrolizumab treatment, respectively. Homologous recombination deficiency test could be used for companion diagnostic of olaparib combination with bevacizumab in first‐line maintenance treatment and niraparib without re‐administration of platinum agents in the treatment of recurrence. The approval of the three drugs has been changing the treatment of gynecologic malignancies. Furthermore, preventive medical care has been covered by insurance since April 2020 for breast and/or ovarian cancer patients with germline BRCA1/2 mutation in Japan. This review article outlines the current status and future prospects of precision medicine for gynecologic hereditary tumors focusing on HBOC and LS.

Vaginal malignant peripheral nerve sheath tumor treated with complete surgical resection and postoperative radiation therapy

AbstractMalignant peripheral nerve sheath tumors (MPNSTs) are neoplasms originating from or differentiating into nerve sheaths of peripheral nerves. Vaginal origin is rare, with only six vaginal primary cases reported to date. A 55‐year‐old woman presented to our hospital with a 7 cm vulvar mass. Tumor biopsy results were suspicious of sarcoma, and pelvic magnetic resonance imaging and hysterofiberscopy showed that the tumor originated from the lower vagina. The mass was transvaginally excised, and histological examination confirmed the diagnosis of a vaginal MPNST with negative surgical margins. The patient underwent radiotherapy because the risk of recurrence was high, owing to the large tumor size and high mitotic index. The patient remained recurrence‐free for 1 year after the primary treatment. This is the first case of a high‐risk vaginal MPNST that avoided early disease recurrence with additional radiotherapy after complete tumor resection.

Retrospective analysis of clinicopathological characteristics of 19 ovarian juvenile granulosa cell tumor cases

AbstractAimTo describe the clinical and pathological characteristics, diagnosis, treatment, and outcomes of juvenile granulosa cell tumor (JGCT).MethodsWe retrospectively analyzed the data of 19 patients with histopathologically confirmed juvenile granulosa cell tumors treated in two medical centers in Wuhan city of China between 1999 and 2019.ResultsTotally, 19 patients were included during the period. The median age at diagnosis was 8.25 years (range, 0.25–28 years). The most common clinical presentation was abdominal pain, five out of 10 prepubertal children presented with precocious puberty. Three patients underwent radical surgery (including total hysterectomy, bilateral salpingo‐oophorectomy, omentectomy, and pelvic and para‐aortic lymphadenectomy), the other 16 patients had fertility‐sparing surgery (cystectomy or ipsilateral salpingo‐oophorectomy with or without omentectomy and lymphadenectomy). Eighteen patients had the international federation of gynecology and obstetrics (FIGO) stage I tumors, one patient had FIGO stage II disease. Twelve patients received postoperative adjuvant chemotherapy. The median follow‐up time from the time of diagnosis was 35 months (range, 13–250 months). One patient experienced relapse and died of the disease 32 months after the initial diagnosis. Eighteen patients were alive and had not experienced recurrence during the follow‐up period. The reproductive age patients that received fertility‐sparing surgery had regular menstruation.ConclusionsA majority of JGCTs are diagnosed as FIGO stage I tumors and have favorable clinical outcomes. Adjuvant chemotherapy seems to improve outcomes for patients with advanced‐stage JGCTs; however, the value of chemotherapy in stage Ic patients is still unknown. Fertility sparing surgery should be considered in young patients who wish to bear children.

Treatment‐related leukemia after taxane and platinum therapy in gynecological cancer patients (Gynecologic Oncology Trial and Investigation Consortium 011)

AbstractAimTo clarify incidence and clinical features of treatment‐related leukemia (TRL) due to taxane/platinum therapy in gynecological cancer patients.MethodsWe conducted a retrospective study of gynecological cancer patients who were diagnosed at facilities participating in the Gynecologic Oncology Trial and Investigation Consortium and started only taxane/platinum therapy as chemotherapy between 2002 and 2006.ResultsThe site of the primary lesion was the ovary in 124, endometrium in 37, and uterine cervix in 4. The regimen of chemotherapy was paclitaxel (T) + carboplatin (C) therapy in 134 and others in 31 patients. The cumulative incidence was 2.4% (4/165), and the incidence was 2.9/1,000 person‐years. All four cases were acute myeloid leukemia. The average total doses of T and C in patients without TRL were 1,693 (SD 1,050) and 4,170 (SD 2,423) mg. For TRL patients, the total T and C doses were, respectively, 1,555 and 3,540 mg, 1,620 and 4,200 mg, 2,130 and 4,700 mg, 3,220 mg and 8,310 mg. The fourth patient received additional 2,415 mg of docetaxel and 2,155 mg of nedaplatin. The intervals from the primary chemotherapy to the onset of TRL were 27, 34, 67, and 114 months. Three patients had no evidence of ovarian cancer. Three patients died of TRL at 4 days, 5 months, and 11 months, one patient remained in remission at 25 months after diagnosis of TRL.ConclusionPatients receiving taxane/platinum therapy should undergo long‐term follow‐up with attention to the development of TRL, even if the gynecologic malignant cancer is in remission.

Case of fetal ovarian juvenile granulosa cell tumor: Complications and management

AbstractA prenatal ovarian juvenile granulosa cell tumor (JGCT) is a rare entity which may present as an intra‐abdominal cyst. Due to its low incidence, optimal management and timing for intervention remain uncertain. This report presents a case of an intra‐abdominal cystic structure in a female fetus, one of the two fetuses in a dichorionic‐diamniotic twin pregnancy, detected during routine fetal sonographic surveillance at 30 weeks of gestation. Further fetal evaluation detected the sonographic triad of an ovarian cystic mass, polyhydramnios and signs of fetal virilizations, requiring us to consider the presence of an atypical, ovarian androgen secreting tumor. Following delivery, acute ovarian torsion and intracystic hemorrhage required emergent surgical intervention, confirming the diagnosis of JGCT. Following surgical treatment, laboratory, clinical, and morphological features improved progressively.

Non‐cancer death causes after ovarian cancer diagnosis: A population‐based cohort

AbstractBackgroundResearch on non‐cancer death causes in ovarian cancer (OC) patients remains limited. We aim to focus on and evaluate the non‐cancer death causes after OC diagnosis.MethodsWe studied 82 590 OC patients diagnosed between 2000 and 2016, using the Surveillance, Epidemiology, and End Results (SEER) Program. Risks of death causes were calculated as standardized mortality ratios.ResultsOf included patients, 48 125 (58.3%) died during the follow‐up period. The highest number of deaths, 21 722 (45.1%), occurred within 1–5 years after OC diagnosis. On the other hand, 19 992 (41.5%) of deaths occurred within a year from ovary cancer diagnosis, 5255 (10.9%) occurred within 5–10 years, and 1156 (2.4%) deaths occurred after more than 10 years following OC diagnosis. Non‐cancer death causes comprise a significant percentage of deaths in OC patients, increasing with time after diagnosis.ConclusionsCardiac diseases, cerebrovascular diseases, and COPD were among the most common non‐cancer death causes after OC diagnosis. Other critical non‐cancer death causes include septicemia and benign neoplasms. Mortality risk differences based on race and age were also highlighted. These findings provide critical insights into how OC survivors should be followed‐up and counseled for relevant future health risks.

Letter to “The application of PAX1 methylation detection and HPV E6/E7 mRNA detection in cervical cancer screening”

Quality of life assessment of cell‐free and concentrated ascites reinfusion therapy during initial treatment for advanced ovarian cancer: A prospective cohort study

AbstractAimCell‐free and concentrated ascites reinfusion therapy (CART) is applied to relieve symptoms in patients with malignant ascites. We performed a prospective cohort study to evaluate the efficacy and safety of CART performed on patients with advanced ovarian and peritoneal cancers with massive ascites during the initial treatment.MethodsFrom April 2018 to July 2020, CART was performed during the initial treatment of 31 patients with advanced ovarian and peritoneal cancers with cancerous ascites. Patient characteristics and clinical information before and after CART were collected. We performed quality of life assessment using the Japanese version of the M.D. Anderson Symptom Inventory (MDASI‐J) 24 h before and after CART.ResultsCART was performed 38 times in 24 patients before or during neoadjuvant chemotherapy and 11 times in 11 patients prior to surgery. Four patients underwent CART before primary surgery and before and/or during chemotherapy. Grade 1–2 fever was observed in 18 of 31 cases (58%), and all were controllable by nonsteroidal anti‐inflammatory drugs. CART did not adversely affect the main treatment, chemotherapy, or surgery. CART significantly improved the MDASI‐J symptom and interference scores within 24 h after the procedure. The symptom and interference scores decreased from 2.4 to 1.8 and from 4.8 to 3.0, respectively.ConclusionsCART can be safely performed and is useful for symptom relief and improvement of general condition prior to initial surgery and during initial chemotherapy in ovarian and peritoneal cancers. Performing CART at the time of initial treatment may facilitate initiation of the main treatment.

DNA methylome profiling identifies novel methylated genes in epithelial ovarian cancer patients with platinum resistance

AbstractAimPlatinum‐based chemotherapy is widely used for epithelial ovarian cancer (EOC). As high as 20–25% of EOC patients will not respond to the initial chemotherapy. Accumulated evidences have implied that DNA methylation may serve as a potential bio‐marker for chemotherapy‐resistant phenotypic screening; however, the pattern underlying primary platinum resistance remains unclear.MethodsReduced representation bisulfite sequencing (RRBS) analysis was performed to identify differences in methylation status between primary platinum‐resistant patients Progression free survival (PFS) (PFS < 6 months, n = 8) and extreme sensitive patients (PFS ≥ 24 months, n = 8). The Qubit 3.0 Fluorometer was used for the quantification of RRBS library. The RRBS library was sequenced on Illumina HiSeq2500 sequencer as 50 bp paired‐end reads.ResultsAfter screening, 94 valid hyper‐/hypo‐methylated regions were identified to be located within 94 gene promoter and exon regions (adjusted q ≤ 0.5), which were primarily associated with cell–cell adhesion, B cell activation and lymphocyte activation according to GO analysis. The 19 differentially methylated regions (DMR) located in the promoter region including TRC‐GCA11‐1, LOC105370912, ANO7P1, DHX4,MSH2, CDCP2, CCNL1, ARHGAP42P2, PRDM13, LOC101928344, USP29, ZIC5,IL1RAPL1, EVX2, ABR, MGRN1, UBALD1, LINC00261, and ISL2 were identified according to the order of P‐values from low to high, of which MSH2, LINC00261, MGRN1, ZIC5, EVX2, CCNL1, and DHX40 were presented to play a variety of roles in cancers process based on the previous studies.ConclusionDNA methylome profiling based on RRBS assay is an effective method for screening aberrantly methylated genes in primary platinum‐resistant patients, which may serve as a potential epigenetic bio‐marker for the prediction of primary platinum resistance.

Annual report of the Committee on Gynecologic Oncology, the Japan Society of Obstetrics and Gynecology: Annual Patient Report for 2018 and Annual Treatment Report for 2013

AbstractTo provide information including the trend of gynecological malignancies in Japan, we hereby present the Annual Patient Report for 2018 and the Annual Treatment Report for 2013, on the outcomes of patients who started treatment in 2013. The Japan Society of Obstetrics and Gynecology maintains an annual tumor registry, where information on gynecological malignancies from various participating institutions is gathered. The data of patients whose treatment with gynecologic malignancies was initiated in 2018 were analyzed retrospectively. Survival of the patients who started treatment with cervical, endometrial, and ovarian cancer in 2013 was analyzed by using the Kaplan–Meier, log‐rank, and Wilcoxson tests. Treatment was initiated in 2018 for 7304 patients with cervical cancer; 11 230 with endometrial cancer; 7031 with ovarian, tubal, and peritoneal cancer; 2072 with ovarian borderline tumors; and with the others (222 vulvar cancer, 159 vaginal cancer, 413 uterine sarcoma, 54 uterine adenosarcoma, and 135 trophoblastic diseases). This clinicopathological information was summarized as the Patient Annual Report. The 5‐year survival rates of the patients with cervical cancer were 93.1%, 75.9%, 59.1%, and 31.2% for Stages I, II, III, and IV, respectively. The 5‐year survival rates for the patients with endometrial cancer were 94.1%, 89.2%, 73.6%, and 25.8% for Stages I, II, III, and IV, respectively. The 5‐year survival rates for the patients with ovarian cancer (surface epithelial‐stromal tumors) were 89.7%, 76.8%, 49.1%, and 32.4% for Stages I, II, III, and IV, respectively. The annual report is important to provide knowledge on gynecological malignancy trends in Japan.

Malignant transformation of mature cystic teratoma of the ovary

AbstractMature cystic teratoma is the most common ovarian germ cell neoplasm. Malignant transformation is a rare occurrence, accounting for 1.5%–2% of cases. Malignant changes can arise from any constituent tissue of a teratoma; however, squamous cell carcinoma is the most common histologic type seen, followed by adenocarcinoma and sarcoma respectively. Tumor marker concentration levels, age, and the tumor maximum diameter are predictive indicators for malignant transformation. Proper diagnosis includes recognizing the possibility of malignant transformation versus excluding other differential options, such as metastasis. Primary cytoreductive surgery, adjuvant chemotherapy, and radiotherapy are the current treatment methods. The aim of the review is to discuss the clinical and pathologic features of malignant transformation within mature cystic teratomas, while reviewing the reported malignant types, differential diagnoses, and treatment options. Data sources include review of pertinent peer‐reviewed literature on malignant transformation of mature cystic teratoma and cases seen in authors' institutional practice. Mature cystic teratomas are a commonly encountered benign ovarian tumor. However, the possibility of malignant transformation should remain in consideration, especially with given clinical or pathologic features: increased patient age, tumor size, or tumor marker levels. Thorough sampling of solid tumor foci can help identify malignant components. Awareness and proper diagnosis, along with early detection and clinical management, shows improved patient outcomes.

Strongyloides stercoralis infestation mimicking recurrence of ovarian cancer in the liver

AbstractOvarian cancer is the most lethal gynecological cancer and can recur in most cases. Surgery is an option for recurrent ovarian cancer. Parasitic infestation disseminated in an immunocompromised host can be fatal. The case is here presented of a female patient diagnosed with early‐stage ovarian cancer. Chemotherapy was initiated for treatment. At the follow‐up examination, masses in the liver suggestive of recurrence were detected on positron emission tomography computed tomography. Surgery was performed. A Strongyloides stercoralis infestation mimicking relapsing ovarian cancer in the liver was diagnosed.

The safety and effectiveness of elective laparoscopic surgery for benign ovarian cysts during pregnancy—Comparison with emergency surgery

AbstractAimRelatively small benign ovarian cysts are conservatively managed in early pregnancy. However, emergency surgery is required should acute abdomen occur. Our study aimed to examine and compare the outcomes of benign ovarian cysts treated with elective laparoscopic surgery or emergency surgery during pregnancy.MethodsFrom 2004 to 2017, we treated 135 pregnant patients (110 elective and 25 emergencies) with benign ovarian cysts at our tertiary perinatal center and compared their surgical and perinatal outcomes.ResultsThere was no significant difference in cyst diameter (7.6 ± 2.5 vs. 6.8 ± 2.1 cm), but cysts <6 cm were significantly more common in emergency (36%) than in elective (15%) cases. Mature teratomas were significantly more common in elective cases (89% vs. 52%) but corpus luteum cysts were more common in emergency cases (0% vs. 32%). The rates of laparoscopic surgery (98.2% vs. 52.0%) and ovarian conservation (99.1% vs. 80.0%) were significantly higher, and post‐surgical hospitalization (4.6 ± 1.3 vs. 9.8 ± 10.5 days) was significantly shorter in elective than in emergency cases. There was no significant difference in the gestational age for delivery (38.9 ± 1.9 vs. 38.4 ± 2.7 weeks), preterm birth rate (12% vs. 20%), or birth weight (2939 ± 469 vs. 3019 ± 510 g).ConclusionsWe cannot state that an emergency surgery during pregnancy is rarely required for small benign ovarian cysts. However, the surgical outcomes were significantly better for elective than for emergency surgery, with no difference in perinatal outcomes. If a benign ovarian cyst is found early in pregnancy, elective laparoscopic surgery may be considered with adequate informed consent.

A patient with a mucinous borderline ovarian tumor after fertility‐sparing surgery in whom puncture fluid cytology on oocyte retrieval led to a diagnosis of recurrence

AbstractThe patient was an unmarried nulliparous 21‐year‐old female who was referred to our hospital with an abdominal mass. Bilateral ovarian tumors with a solid component were detected and both were suspected to be ovarian cancer. Since the patient strongly wished to preserve fertility, we performed left salpingo‐oophorectomy, right cystectomy, and omentectomy. A postoperative histopathological examination revealed that the bilateral ovarian tumors were mucinous borderline tumors. The patient selected oocyte cryopreservation. Oocyte retrieval from the right ovary was performed 2 years after surgery, and six oocytes were obtained. The puncture of a small cyst revealed mucinous fluid, not normal follicular fluid; therefore, puncture fluid cytology was performed. A recurrent mucinous borderline ovarian tumor was suspected. Right salpingo‐oophorectomy was performed and a recurrent mucinous borderline ovarian tumor was diagnosed. Puncture fluid properties need to be considered when there is an opportunity for oocyte retrieval after fertility‐sparing surgery.

Tissue factor pathway inhibitor 2: A potential diagnostic marker for discriminating benign from malignant ovarian tumors

AbstractObjectivesCarbohydrate antigen 125 (CA125), CA19‐9, carcinoembryonic antigen (CEA), human epididymis protein 4 (HE4), and the Risk of Ovarian Malignancy Algorithm (ROMA) are widely used as tumor markers and algorithms for the diagnosis of ovarian cancer (OC). Tissue factor pathway inhibitor 2 (TFPI2) has been developed as a potential serodiagnostic marker for OC in Japan. The aim of this study is to evaluate the diagnostic accuracy of the six markers alone and in combination to find the best marker for discriminating between benign and malignant ovarian tumors.MethodsFrozen serum samples collected from 484 patients were divided into three groups based on histopathological results: OC (n = 119), borderline ovarian tumors (BR) (n = 48), and benign ovarian tumors (BN) (n = 317). Diagnostic accuracy was calculated with an area under a receiver operating characteristic (AUC) curve.ResultsTFPI2 achieved the highest discrimination between the OC + BR group versus the BN group (AUC 0.8076). ROMA values best discriminated patients with OC from those with BN (AUC, 0.8966), which was equivalent to TFPI2 (AUC, 0.8937). For discriminating the OC group from the BR + BN group, the highest AUC value was achieved by ROMA values (AUC, 0.8884), and TFPI2 also showed comparable diagnostic accuracy (AUC, 0.8845). Combining TFPI2 with ROMA had the highest AUC (0.8420–0.9357).ConclusionTFPI2 may be a clinically useful single marker comparable to conventional ROMA values for discriminating between benign and malignant ovarian tumors.

Association of BRCA1/2 mutations with prognosis and surgical cytoreduction outcomes in ovarian cancer patients: An updated meta‐analysis

AbstractAimThis meta‐analysis was conducted to evaluate the impact of BRCA mutations on survival outcomes of ovarian cancer patients and assess whether the BRCA status was an independent predictor of complete cytoreduction.MethodsWe searched the PubMed, Cochrane, EMBASE, Scopus, Web of Science, and Google Scholar databases for studies that evaluated the associations among BRCA mutations, ovarian cancer survival and surgical cytoreduction before August 2021 based on specific inclusion and exclusion criteria.ResultsWe identified 61 articles that compared the clinical features, survival outcomes, and optimal surgical cytoreduction rates between BRCA‐positive patients and BRCA‐negative patients. The results showed that BRCA mutation carriers were diagnosed with ovarian cancer at a younger age than the age at which nonmutation carriers were diagnosed. In addition, BRCA mutation carriers were more likely to be in the International Federation of Gynecology and Obstetrics (FIGO) stage III‐IV, and the pathological grade was commonly grade 3. The pathological type of BRCA mutation carriers was more likely to be high‐grade serous carcinoma. Patients with BRCA mutations had higher response rates to platinum‐based chemotherapy than the noncarriers. However, patients in both groups had equivalent rates of surgical cytoreduction, and BRCA‐positive patients had longer overall survival (OS) time (HR = 0.65; 95% confidence interval [CI]: 0.59, 0.73; p < 0.001) and longer progression‐free survival (PFS) (HR = 0.72; 95% CI: 0.63, 0.82; p < 0.001).ConclusionBRCA mutations appear to be associated with improved OS and PFS in patients with ovarian cancer. However, we did not find any difference in the surgical resection rate between participants in the two groups.

Clinical outcomes of transarterial chemotherapy and embolization for vaginal cancer

AbstractAimWe report clinical outcomes of transarterial embolization in 19 cases of vaginal cancer.MethodsFrom August 2011 to October 2019, 19 patients with histologically diagnosed vaginal cancer were identified in our department. Transarterial chemotherapy and embolization was performed for all patients. Patient characteristics, treatment plans and the clinical outcomes, were recorded.ResultsAmong 19 identified cases, nine of them are squamous cell carcinoma, five of adenocarcinoma, one of adenosquamous carcinoma, two of vaginal malignant melanoma, one leiomyosarcoma and one of stromal sarcoma. Transarterial chemotherapy and embolization was successfully performed in all patients. No related complication was found after intervention treatment. Besides, eight patients received adjuvant chemotherapy, four received both adjuvant chemotherapy and radiotherapy and seven received no therapies. Four patients were cured and seven were stable during follow‐up.ConclusionTransarterial embolization appears safe and effective for vaginal cancer, with a currently acceptable prognosis.

Pseudo‐pseudo Meig's syndrome presenting as an acute surgical abdomen: A rare entity and review of the literature

AbstractAimPseudo‐pseudo Meigs' syndrome is a rare entity of systemic lupus erythematosus, which is defined with the combination of pleural effusion, elevated serum CA‐125 levels, and ascites. It has similar clinical aspects with gynecological malignancies which may lead gynecologists to perform unnecessary surgeries and lab workouts. This review seeks to point out the importance of diagnosing pseudo‐pseudo Meig's syndrome (PPMS) and endeavors to inform gynecologists about the differential diagnoses.MethodsThis article includes a review of the literature on different cases of PPMS. We searched the PubMed database using the search terms in various combinations “Pseudo‐pseudo Meig's syndrome,” “Tjalma syndrome,” and “SLE.”ResultsAccording to the current literature, a majority of internal medicine specialists recognized this clinical condition in the past few years and discussed PPMS as a new onset of systemic lupus erythematosus. PPMS is one of the disregarding entities where gynecologists do not consider it as a differential diagnosis in case of less awareness. When a gynecologist evaluates ascites manifesting as acute abdomen; ectopic pregnancy, ovarian hyperstimulation syndrome, cyst rupture, and malignancy come to mind first. Four‐thirds of those patients evaluated by gynecologists were performed hysterectomy leading to unnecessary interventions and economic burden on the health system.ConclusionAlthough the mechanism is unrevealed and remains unclear, PPMS has been noticed in the literature for the past few years. In order to prevent unnecessary interventions, this syndrome should be considered as a differential diagnosis.

Recurrent primary ovarian leiomyosarcoma preconception, pregnancy, delivery, and puerperal management: A case report and literature review

AbstractA primary ovarian leiomyosarcoma (POLMS) is a rare malignant tumor of the ovary. Herein, we report a patient with an early‐stage POLMS who underwent unilateral adnexectomy in our department with a subsequent pregnancy, delivery, and tumor recurrence. In this case, the patient was a 29‐year‐old female with a complaint of abdominal distention who underwent a right adnexectomy for a solid tumor in the right ovary. The pathological diagnosis was a stage IA leiomyosarcoma of the right ovary. One month later, a recurrence in the left ovary tumor was diagnosed. The patient did not agree to further treatment. She subsequently achieved a spontaneous pregnancy and had an uneventful pregnancy and delivery at term. During the puerperium, she underwent radical surgery and chemotherapy with the recommended follow‐up evaluation. The literature review shows the pathogenesis of POLMS has not been established. There are no specific tumor markers, and it is difficult to distinguish the nature and origin of the tumor with imaging modalities, thus, early diagnosis is difficult. The malignancy rate is high, and the prognosis of advanced tumors is poor. To properly counsel patients to optimize treatment, more reports of cases, the disease course, treatments, and outcomes are needed.

Optimizing regional chemotherapy for epithelial ovarian cancer

AbstractAimThe response with intravenous chemotherapy using cisplatin and paclitaxel in patients with advanced ovarian cancer is often substantial. However, this regression of the malignancy is not durable, and a majority of patients succumb to this disease process. It is possible that alternative types of chemotherapy and alternative routes of chemotherapy administration can improve the results of treatment and perhaps, reduce the morbidity and mortality that patients experience.MethodsRegional chemotherapy treatments previously presented in the ovarian cancer literature were reviewed and critically analyzed. New methods for chemotherapy delivery for both advanced primary and recurrent ovarian cancer were reviewed. This included hyperthermic intraperitoneal chemotherapy (HIPEC), early postoperative intraperitoneal chemotherapy (EPIC), and normothermic intraperitoneal chemotherapy (NIPEC) long‐term.ResultsAn important addition to perioperative chemotherapy delivery is the simultaneous use of heat with intraperitoneal drug delivery after a complete cytoreductive surgery. Drugs to be considered for HIPEC are cisplatin, gemcitabine, and melphalan. For EPIC, chemotherapy agents to consider include paclitaxel, pemetrexed, gemcitabine, and liposomal doxorubicin. For NIPEC, paclitaxel is the drug of choice usually combined with a systemic agent as bidirectional chemotherapy. Also, pemetrexed, gemcitabine, and liposomal doxorubicin are drugs to be considered for NIPEC in phase I/II trials.ConclusionsInnovative regimens of regional chemotherapy may improve the outcome of patients with advanced ovarian cancer. These chemotherapy treatments must be integrated with complete cytoreductive surgery and the availability of peritoneal access for repeated delivery of chemotherapy solutions.

T‐cell activation is associated with high‐grade serous ovarian cancer survival

AbstractAimHigh‐grade serous ovarian cancer (HGSOC) is an aggressive disease that is largely resistant to today's immunotherapies. Here, we aimed to investigate the prognostic significance of CTLA4, PD‐1, and T‐cell activation status in HGSOC.MethodsUsing a publicly accessed microarray dataset including 260 HGSOC samples, we calculated Kaplan–Meier survival curves for overall survival (OS), evaluated associations with multivariate Cox regression models to evaluate the associations, and summarized using a hazard ratio (HR). The correlations between PD‐1 gene expression and that of other genes were calculated by Pearson correlation.ResultsMultivariate survival analyses showed that high PD‐1 expression but not CTLA4 was associated with longer OS (HR = 0.69; 95% confidence interval [CI] = 0.52–0.91; p = 0.01), and that higher T‐cell activation score was associated with better outcome (HR = 0.74; 95% confidence interval [CI] = 0.58–0.95; p = 0.02). The top three PD‐1 highly correlated genes were SIRPG (r = 0.90, p < 2E‐16), FASL (r = 0.89, p < 2E‐16), and CD8a (r = 0.87, p < 2E‐16). HGSOC patients' OS is positively associated T‐cell activation score and PD‐1 expression but not CTLA4.ConclusionT cell activation score may serve as a candidate for personalized immunotherapy in HGSOC. The application of anti‐PD‐1 therapy to HGSOC should be cautious.

CTLA‐4 polymorphism contributes to the genetic susceptibility of epithelial ovarian cancer

AbstractAimCytotoxic T‐lymphocyte antigen‐4 (CTLA‐4), an inhibitory molecule on T‐cells, plays a key role in tumorigenesis and progression. In the present study, we investigated the effects of three polymorphisms in the CTLA‐4 gene on the risk of epithelial ovarian cancer and the clinical outcomes of patients.MethodsA case–control study was performed in 527 epithelial ovarian cancer patients and 532 controls. Genotypes of three polymorphisms were determined by polymerase chain reaction/ligase detection reaction. A survival analysis was performed in 346 patients who were followed up for more than 3 years and 208 patients who were followed up for more than 5 years.ResultsThere were significant differences in the genotype and allele distribution frequencies of the rs5742909 C/T polymorphism in CTLA‐4 between patients and controls (p = 0.009 and p = 0.04, respectively). Compared with the CC genotype, the CT + TT genotype may significantly decrease the risk of developing epithelial ovarian cancer (OR = 0.69, 95% CI = 0.52–0.91). However, no significant association between the rs231775 G/A and rs3087243 G/A polymorphisms and epithelial ovarian cancer risk was observed. The survival analysis showed that three polymorphisms may not be related to the clinical outcomes of patients.ConclusionOur results suggested that the rs5742909 C/T polymorphism of CTLA‐4 may decrease the genetic susceptibility to epithelial ovarian cancer among northern Chinese women.

LncRNA HCG11 represses ovarian cancer cell growth via AKT signaling pathway

AbstractAimOvarian cancer is a main contributor of cancer‐relevant deaths among women worldwide due to high incidence and mortality. Mounting evidence has unveiled that lncRNAs play critical roles in malignancies, including ovarian cancer. Although the tumor suppressor function of HCG11 in prostate cancer and glioma has been proved, investigations on HCG11 role in ovarian cancer are still scarce.MethodsGene or protein expression was quantified by RT‐qPCR or western blot. HCG11 effects on ovarian cancer were assessed by functional assays. Bioinformatics analysis and mechanism experiments were implemented to identify the association among HCG11, miR‐1270, and PTEN.ResultsHCG11 was weakly expressed in ovarian cancer and functioned as a tumor suppressor in ovarian cancer by retarding cell proliferation, migration, and EMT. Besides, HCG11 could bind to miR‐1270 and PTEN was a target gene of miR‐1270. Mechanically, HCG11 competitively bound with miR‐1270 to upregulate PTEN. From rescue experiments, HCG11 impeded AKT/mTOR pathway to retard ovarian cancer cell growth by miR‐1270/PTEN.ConclusionsHCG11 was a tumor suppressor in ovarian cancer cells and additionally, HCG11 regulated AKT/mTOR pathway to hinder ovarian cancer cell growth via modulating miR‐1270/PTEN, indicating that HCG11 may represent a promising target for effective treatment of ovarian cancer patients.

Primary malignant melanoma of the uterine cervix or vagina which were successfully treated with nivolumab

AbstractPrimary malignant melanomas (MM) originating from the gynecological tract are rare. They respond poorly to immunotherapy when compared with cutaneous MM. This study reports two cases. The first is of a 54‐year‐old woman with a cervical amelanotic polypoid mass who was diagnosed as having stage IB1 cervical melanoma according to the International Federation of Gynecology and Obstetrics system. At 17 months post‐surgery, a computed tomography examination revealed recurrence of a 68 mm pelvic tumor. The second case is of a 37‐year‐old woman with a 7 cm hemorrhagic mass on the vaginal wall. The patient was diagnosed as having stage IV vaginal melanoma according to the American Joint Committee on Cancer definition. Both patients received nivolumab therapy, programmed cell death receptor 1 monoclonal antibodies, and the tumors almost disappeared. These cases may add the possibility of using colposcopy with narrow‐band imaging and positron‐emission tomography to diagnose and evaluate primary MM.

Rare case of uterine cervix lymphoma with spontaneous regression: Case report

AbstractPrimary malignant lymphoma rarely occurs in the female reproductive tract, because of that they are often misdiagnosed. Lymphoma spontaneous regression is even rarer, but it is possible behavior of this disease. A case of 54‐year‐old female patient with a primary diffuse large B‐cell lymphoma of the cervix is presented. First assumption was sarcoma or atypical adenocarcinoma; biopsies have been inconclusive and, after a partial spontaneous regression, diagnosis of lymphoma was possible only after surgery. The diagnosis was a real challenge for clinicians, radiologists and pathologists for both localization and behavior. Difficulties in diagnosis led to an over‐treatment: a laparotomic bilateral hysteron salpingectomy with lymphadenectomy was performed, while chemotherapy alone would have been the right approach. Considering that prognosis and treatment of primary malignant lymphoma of the cervix are completely different than those of other malignant tumors of the uterus, this disease should be considered in the differential diagnosis.

Uterine cervical squamous cell carcinoma with reactive multinucleated giant cells expressing cluster of differentiation 204: A case report and literature review

AbstractUterine cervical squamous cell carcinoma (SCC) with reactive multinucleated giant cells (MGC) is extremely rare. Here we present the case of a 49‐year‐old woman treated with radical hysterectomy, bilateral adnexectomy and lymph node dissection. Histologically, the cervical tumor was diagnosed as nonkeratinizing SCC of pT1b1N0M0, with negative surgical margin. Many MGC including osteoclast‐like giant cells with immunohistochemical expression of cluster of differentiation 204, a marker for the M2 macrophage, were present around the tumor nests. The patient received postoperative radiation therapy and achieved 22 months of disease‐free survival after the surgery. M2 macrophages promote aggressiveness of the carcinoma and it is suggested that SCC of the cervix with reactive MGC might have poor prognosis; however, our case paradoxically showed a favorable course. From literature review of six cases, including our case, the effect of MGC‐reaction may vary with respect to other factors, such as age, cancer stage or histological type.

The application of PAX1 methylation detection and HPV E6/E7 mRNA detection in cervical cancer screening

AbstractAimWe aimed to explore the application of PAX1 methylation and human papillomavirus (HPV) E6/E7 mRNA detection in cervical cancer screening and to compare the efficacy with high‐risk (HR)‐HPV detection.Patients and methodsThe cervical exfoliative cytology samples of 337 patients were collected, including 70 cases of cervical inflammation, 72 cases of low‐grade squamous intraepithelial lesions, 97 cases of high‐grade squamous intraepithelial lesions, and 98 cases of cervical carcinoma. The PAX1 gene methylation (PAX1) status was detected by multiple quantitative PCR, HPV E6/E7 mRNA (E6/E7) was detected by QuantiVirus detection, and HR‐HPV (HPV) was detected by the Cobas 4800 detection system. The sensitivities, specificities, and accuracies were validated in the testing set.ResultsThe sensitivities of the HPV, HPV E6/E7, and PAX1 testing were 89.23%, 84.10%, and 86.67%, respectively, which all maintained a high level. In contrast, the specificities of the HPV, E6/E7, and PAX1 testing were only 19.10%, 37.32%, and 97.18% (in pairwise comparisons, p = 0.000). The AUC of PAX1 (0.919) was significantly larger than that of HPV (0.541) and E6/E7 detection (0.607) (p < 0.0001). In addition, the AUC areas of all combined parallel testing were lower than that of single PAX1 test (p < 0.05).ConclusionThe diagnostic efficacy of E6/E7 detection and PAX1 detection was better than that of HPV detection, especially for PAX1 detection.

Human papillomavirus vaccination: Good clinical practice recommendations from the Federation of Obstetric and Gynecological Societies of India

AbstractHuman papillomavirus (HPV) vaccination offers an excellent prospect for the primary prevention of cervical cancer. The bivalent and quadrivalent vaccines are both available in India. The nonavalent vaccine is licensed but not yet available. However, there still remain controversies regarding the vaccination of older women, immunocompromised females and other special groups. To provide recommendations for HPV vaccination in India. The Federation of Obstetric and Gynecological Societies of India (FOGSI) convened an expert group on cervical cancer prevention to formulate good clinical practice recommendations (GCPR) with respect to vaccine efficacy and safety, target groups, optimal timing and dosing schedules. HPV vaccines are licensed for females aged 9–45 years in India and have been seen to be safe and effective. FOGSI recommends HPV vaccination of all girls <15 years of age as the best target group, in whom two‐doses at an interval of 6 months, extendable to 18 months, are recommended. Three‐doses are recommended in girls >15 years of age, immunocompromised persons and sexual assault survivors. Older women and women with abnormal screening results may be vaccinated with an understanding that vaccination does not protect against already acquired infections and screening has to continue. Single‐dose vaccination results are promising. Increased awareness is required to reduce vaccine hesitancy. HPV vaccination should be the priority to achieve the elimination of cervical cancer. The introduction of affordable HPV vaccines and reduced dose schedules will improve coverage.

Rare case of tonsillar and subcutaneous metastasis from neuroendocrine cervical cancer

AbstractNeuroendocrine cervical carcinoma (NECC) is a rare type of cervical cancer, with high tendency of lymphatic and distant metastasis and poor prognosis. Herein, we reported a rare case of relapsed NECC metastasizing to palatine tonsil and subcutaneous adipose tissue in multiple regions, which reflects the aggressive biological behavior of NECC.

Knowledge about the human papillomavirus among high school and university students a comprehensive questionnaire study from Southeast Turkey

AbstractAimTo investigate the level of knowledge among high school and university students about the human papillomavirus (HPV) and its vaccine.MethodsOur study included 3039 Grade 9–12 students from 12 high schools and university students enrolled in medical and non‐medical departments. The students completed a 30‐item questionnaire, which included three demographic items (sex, age and grade) and measured knowledge regarding HPV, HPV vaccine, smear test and cervical cancer. Students responded by selecting one of the choices “true/false/I don't know.”ResultsOne thousand seven hundred and forty eight high school students (57.5%) and 1291 university students (42.5%) completed the questionnaire. One thousand three hundred and fourty one students were male (44.1%) and 1698 were female (55.9%). Mean age was 18.8 (min: 14 max: 33). The university group had significantly more correct responses (P = 0.001). The high school group had significantly more unknown responses (P = 0.001). In both groups, female and male students had comparable correct responses (High school; female: 25.28%, male: 24.45%, P = 0.42; University; female: 62.46%, male: 63.09%, P = 0.35). While medical students had more correct responses than both nursing students and students from non‐medical university departments, nursing students had more correct responses than students from the non‐medical university departments (P = 0.001).ConclusionKnowledge about HPV is limited in adolescence, which marks the beginning of sexual activity. Educational programs targeted at adolescents are needed to negate the increasing rate of HPV‐related gynecological cancers in our population. The HPV vaccine should urgently be introduced to the routine immunization schedule.

Reconstructed uterine length is critical for the prevention of cervical stenosis following abdominal trachelectomy in cervical cancer patients

AbstractAimAlthough the procedure of abdominal trachelectomy has been remarkably improved, preventing subsequent cervical stenosis remains challenging. In this study, we analyzed the clinicopathological risk factors for cervical stenosis to explore the appropriate surgical procedures for the prevention of cervical stenosis following trachelectomy.MethodsThirty‐two patients who underwent abdominal extended and radical trachelectomy were assessed retrospectively (median follow‐up period = 33 months). To evaluate the risk factors, the clinicopathological factors were analyzed by univariate and multivariate analyses. The reconstructed uterine length (UtL), that is, the length between the vaginal end of the neo‐cervix and the uterine fundus, was measured by transvaginal ultrasound after surgery. The cut‐off value for the UtL was assessed by a receiver operating characteristic (ROC) curve analysis.ResultsCervical stenosis of any grade was observed in 12 patients (grade 1 = 9, grade 3b = 3). Among the various clinicopathological factors, the UtL and cervical length (CL) were significantly related to cervical stenosis following trachelectomy. The multivariate analysis revealed that the UtL, but not CL, is an independent risk factor for stenosis. The ROC curve analysis revealed that stenosis was significantly more likely to occur in patients with a UtL shorter than 53 mm (area under the ROC curve = 0.902). UtL in the patients who became pregnant was longer than that in the patients who did not. No evidence of recurrent cancer was observed during the follow‐up period.ConclusionOur proposed method may provide a functional reconstructed uterus with preserving fertility by remaining UtL more than 53 mm.

A case of cervical adenocarcinoma arising from endometriosis in the absence of human papilloma virus infection

AbstractEndometriosis‐related cervical neoplasms are rare, and their clinicopathological features and association with human papilloma virus infection are unclear. A postmenopausal woman with recently diagnosed cervical adenocarcinoma was referred to our hospital. After further investigation, we suspected a stage IIB neoplasm that originated from endometriosis of the cervix or left parametrium. A radical hysterectomy was performed, and pathological examination confirmed a stage IIB cervical endometrioid carcinoma arising from the endometriosis in the cervix to the left parametrium that invaded the cervix; human papilloma virus infection of tumor cells was not detected. Endometriosis‐related neoplasms can occur in the cervix or parametrium and present as cervical cancer. The neoplasm described here was not associated with human papilloma virus infection.

Thermo‐coagulation versus cryotherapy for treatment of cervical precancers: A prospective analytical study in a low‐resource African setting

AbstractAimsTo evaluate the outcomes of cryotherapy and thermo‐coagulation in the treatment of cervical precancers.MethodProspective analytical study. Women who screened positive to visual inspection with acetic acid and confirmed by colposcopy using the Swede's score were randomized to receive either cryotherapy or thermo‐coagulation. Participants were re‐evaluated 6 months later.ResultsA total of 11 124 women were screened. Only 1023 of the 1294 colposcopically confirmed positive cases were eligible for ablative therapy. Five hundred and twelve women received cryotherapy while 511 women received thermo‐coagulation. Cryotherapy had similar cure rate with thermo‐coagulation (85.5 vs 89.2%, P = 0.09). The mean patient satisfaction score for thermo‐coagulation was higher than that for cryotherapy (3.9 ± 1.3 vs 2.8 ± 1.7; P < 0.0001). The mean duration of treatment per patient was higher for cryotherapy than thermo‐coagulation (660.0 ± 0.0 vs 50.9 ± 15.3 s, P < 0.0001). The mean cost of treatment per patient was significantly higher for cryotherapy than for thermo‐coagulation (2613.1 ± 254.9 vs 533.2 ± 45.2 Nigerian Naira, P < 0.0001). Higher proportion of women who had thermo‐coagulation reported no side effect (55.2 vs 12.5%, P < 0.0001).ConclusionCryotherapy and thermo‐coagulation have similar efficacy in the treatment of cervical precancers. Thermo‐coagulation offers lower cost and lower duration of treatment, less side effects and higher patient satisfaction than cryotherapy. Thermo‐coagulation should be the recommended ablative treatment method for low‐resource settings of the world.

Retrospective Study of the Risk of Progression to Squamous Cell Carcinoma of Vulvar Lichen Planus Forms Isolated or Associated With Other Dermatoses

ABSTRACT Aims The aim of the study was to examine the potential risk of vulvar lichen planus (LP), alone or associated with lichen sclerosus (LS) or lichen simplex chronicus (LSC), to evolve towards vulvar cancer (VSCC). Methods We retrospectively investigated the incidence of vulvar cancer in women diagnosed with LP, alone or associated with LS and LSC, between 2007 and 2022. Results We retrieved the data of 77 women with LP with a mean age of 63.5 ± 11.9 years old. Of these, 53 had LP, 19 had LP+LS, and 5 had LP+LSC. Ultrapotent topical corticosteroids were the first‐line treatment. The mean follow‐up time was 45 ± 30.14 months, during which four patients developed VSCC (5.19%). All four cases were found to be associated with the presence of multiple lichen, and the frequency of developing a neoplasm in the presence of LS or LSC superimposed on LP was found to be significant with Fisher's exact test ( p  = 0.0079). Conclusion Analyzing our data, we can point out a concrete possibility regarding the relationship between multiple lichen and VSCC compared to LP alone. However, the sample size is too small to allow definitive conclusions to be drawn, and multicenter studies would, therefore, be desirable in the future both to examine more thoroughly and in large numbers the relationship between LP, multiple lichen, and vulvar cancer and to find new treatment and follow‐up strategies for pathogenesis.

Clinical characteristics and survival outcome of vulvar cancer in South Korea: A nationwide study from the Cancer Public Library Database

Abstract Objective Vulvar cancer, although rare, presents clinical challenges due to diverse histological subtypes and varying prognoses. This study aimed to examine the clinical characteristics and survival outcomes of vulvar cancer in South Korea. Methods A retrospective cohort study was conducted using data from the Cancer Public Library Database, which includes information from the Korea National Cancer Incidence Database, Statistics Korea, and National Health Insurance databases. The study analyzed data from South Korean women diagnosed with vulvar cancer between 2014 and 2016. Results Out of 1242 initial patients, 292 met the inclusion criteria. The untreated group ( n  = 62) had a higher proportion of patients aged 80 and above (35.5%) and a higher mean Charlson Comorbidity Index (CCI) score compared to the treatment group ( n  = 230). The treatment group showed significantly higher survival probability (adjusted HR 0.358, 95% CI: 0.24–0.54) compared to the untreated group. Surgical intervention alone reduced mortality risk significantly (adjusted HR 0.20, 95% CI: 0.12–0.33), particularly among those diagnosed at an earlier clinical stage. Histologically, basal cell carcinoma had the highest survival probability with a significantly lower mortality risk than squamous cell carcinoma (adjusted HR 0.11, 95% CI: 0.02–0.82). Adenocarcinoma also showed improved survival outcomes (adjusted HR 0.42, 95% CI: 0.19–0.94). Conclusion The study emphasizes the importance of early diagnosis and surgical treatment in improving survival outcomes for vulvar cancer patients. It also highlights the need to consider demographic and clinical factors in treatment planning and calls for region‐specific studies to address unique epidemiological patterns.

Sub‐regional skin grafting for perineal resurfacing after excision of superficial vulvar tumors: An excellent method to achieve an aesthetically pleasing appearance

AbstractObjectiveTo investigate the effect of sub‐regional split‐thickness skin grafting in perineal resurfacing.MethodsA single‐center retrospective study was conducted in the Genital Plastic Surgery Center. Detailed clinical data of 14 consecutive patients who underwent split‐thickness skin grafting after vulvar tumor resection from February 2013 to June 2022 were analyzed. Clinical data, postoperative photographs, scoring of vulvar appearance, and questionnaire results of the Female Sexual Function Index before and after surgery were analyzed.ResultsThe patients had sub‐regional split‐thickness skin grafting ranging from 7 × 8 cm to 11 × 12 cm (88.86 ± 24.99 cm2). After a follow‐up of 8.21 ± 2.22 months (mean ± SD), all patients had a three‐dimensional and aesthetically pleasing vulva and high scoring of vulvar appearance (mean ± SD, 4.43 ± 0.65). All patients had good healing of both the recipient and donor sites without major complications. Only one patient had minor dehiscence in the perineal region and recovered soon after proper treatment. The scores of the Female Sexual Function Index were significantly improved after surgery. Among the included domains, scores of “desire,” “arousal,” “orgasm” and “satisfaction” increased significantly after surgery (p value <0.05).ConclusionsSub‐regional split‐thickness skin grafting could achieve excellent cosmetic outcomes with few complications in perineal reconstruction after the excision of superficial vulvar tumors. It can provide an aesthetically pleasing appearance in the vulvar region and improve female sexual function to some extent. In general, sub‐regional split‐thickness skin grafting could be a recommended reconstructive option to repair vulvar defects.

Postpartum regression of human papillomavirus‐related vulvar cancer: A case report

AbstractWe report a case of a 23‐year‐old pregnant woman (gravida 2 para 0, pregnancy 33 weeks and 3 days) with a history of laser ablation for cervical intraepithelial neoplasia‐3 at 22 years. At initial visit, a 2 × 2 × 1‐cm elevated mass was found on right labia majora. Biopsy results revealed squamous cell carcinoma of right labia; immunostaining revealed p16 positivity. Patient was diagnosed with human papillomavirus‐related vulvar cancer. Selective cesarean section was performed at 36 weeks and 4 days of gestation. Postoperative histopathological diagnosis of squamous cell carcinoma, and 1.7‐mm deep infiltrations led to vulvar cancer stage IB diagnosis. Reduction operation was performed, and postoperative follow‐up of 1 year and 8 months revealed no recurrence. These results emphasize that small vulvar tumors during pregnancy should not be underestimated and histological examinations should be performed without hesitation. Careful observation and evaluation of tumors is necessary during pregnancy and after delivery because they may shrink postdelivery.

Myoepithelioma‐like tumors of the vulvar region: A case report and review of the literature

AbstractMyoepithelioma‐like tumors of the vulvar region (MELTVR) is a kind of solid tumor newly recognized in recent years, which is characterized by mesenchymal tumors of adult female vulva. The histopathology is similar to myoepithelioma, but the immunohistochemical phenotype and genetic changes are different from myoepithelioma. It usually has clear boundary and partial capsule, mixed with two forms of cells (epithelioid and spindle), the cells are mild, the nucleoli are clear, mitoses are rare, some cases have myxoid differentiation. In this article, a case of MELTVR diagnosed in our hospital is discussed. The patient was a 43‐year‐old female who finds a neoplasm in the pubic tubercle 4 months ago. Local resection was performed. Pathological examination showed that the boundary of the tumor was clear with partial capsule. The cells were arranged in cords or nests, and partially infiltrated the surrounding adipocytes. The tumor cells had two morphologies, epithelioid or spindle shaped. The spindle type cells were dominant, with bright cytoplasm, obvious nucleoli, rare nuclear mitosis (about 1/10HPF), and no necrosis was observed. Immunohistochemically, the tumor cells were positive for vimentin, epithelial membrane antigen, estrogen receptor, progestogen receptor, calponin and were partially positive for cathepsin k. INI1/SMARCB1 expression was deficient. There was no recurrence or metastasis during the 8‐month‐long follow‐up. The unique feature of this case was that the site of the disease was not the vulva, but in front of the pubic tubercle, there was no large amount of mucus production, and the cytoplasm of most tumor cells was transparent. Due to our limited knowledge of MELTVR, its pathogenesis and tissue origin are not clear. Clinicians should be aware of such potential patients.

Impact of COVID‐19 on cervical cancer screening in Japan: A survey of population‐based screening in urban Japan by the Japan Society of Gynecologic Oncology

AbstractAimTo assess the impact of COVID‐19 on cervical cancer screening.MethodThe Japanese Society of Gynecologic Oncology launched COVID‐19 Task Force surveyed the municipalities in urban areas of Japan. Questionnaires were sent to 20 ordinance‐designated cities and 23 wards of Tokyo metropolitan area in Japan via telephone and mail in January 2021. An additional survey was conducted in March and April 2021, counted the monthly checkups in 2020 and, as a control data, the number of monthly checkups in 2019. “The State of Emergency” between April 7 and May 25, 2020, included 13 prefectures. The data collected in this research involved the number of screenings only. The chi‐square test was performed for statistical analysis.ResultsThe number of cancer screenings from March to August, with May being the month with the lowest number of screenings, was less than 50% of that in the previous year. In particular, the drop in the number of cancer screenings in the “Prefectures operating under special safety precautions” was remarkable and significantly lower than that in other Prefectures. However, after August, the number recovered to the usual level, despite the second wave of the pandemic occurring nationwide. The initial “the State of Emergency” caused a significant decrease in the number of people receiving population‐based screenings, but the recovery has been remarkable, and the total number is expected to be the same as in previous years.ConclusionThe initial “the State of Emergency” caused a significant decrease in the number of people receiving population‐based screenings.

Rethinking the significance of surgery for uterine cervical cancer

AbstractBackgroundTreatment strategies based on histological subtypes are unestablished.AimsRethinking the significance of surgery for uterine cervical cancer.MethodsUsing the database of cervical cancer stages IB–IIB with extensive hysterectomy (Federation of Gynecology and Obstetrics [FIGO] 2008) established by the Japanese Gynecologic Oncology Group network, we conducted a clinicopathological study of cervical cancer cases reclassified according to the FIGO 2018 staging. In stage IB (FIGO 2018) cervical cancer patients, there was no significant difference in treatment outcome according to histological type, but in stages IIA, IIB, and IIIC1 (FIGO 2018), the treatment outcome of nonsquamous cell carcinoma was significantly worse than that of squamous cell carcinoma. Considering post‐treatment health care, it is important to consider ovarian preservation in young patients with cervical cancer, up to stage IIA (FIGO 2018) for squamous cell carcinoma and stage IB1 (FIGO 2018) for nonsquamous cell carcinoma, after careful evaluation of clinicopathological factors before surgery.DiscussionLocally advanced adenocarcinoma of the cervix is a rare and refractory cancer that has been shown to have low radiosensitivity, and its treatment outcome is still unsatisfactory. A new therapeutic strategy involving multidisciplinary treatment in combination with perioperative chemotherapy at a facility that can provide highly curative surgical treatment is desired.ConclusionMinimally invasive surgery is being introduced for the treatment of early‐stage cervical cancer. However, the number of eligible cases should be expanded in a phased manner, based on an objective evaluation of surgical outcomes at the facilities. Omics analysis may be useful to develop a new treatment for human papillomavirus nonrelated cervical cancer, represented by gastric mucinous carcinoma.

Inhibition of monoacylglycerol lipase restrains proliferation, migration, invasion, tumor growth and induces apoptosis in cervical cancer

AbstractAimCervical cancer is one of common diseases among women. There are limited therapies for patients with metastatic or recurrent cervical cancer. This study sought to explore the role of monoacylglycerol lipase (MAGL), an important metabolic enzyme, in cervical cancer progression.MethodsIn in vitro experiments, MAGL expression was inhibited by si‐MAGL or JZL184 in cervical cancer cells. Quantitative real‐time polymerase chain reaction and western blotting were performed to measure the expression of target molecules. Proliferation of cervical cancer cells was assessed by CCK‐8 and colony formation assays. Apoptosis and cell cycle progression were evaluated by flow cytometry. The migration and invasion were detected by transwell assay. The in vivo tumor growth was detected in nude mice. TUNEL was utilized to observe apoptotic cells in tumor tissues.ResultsMAGL was upregulated in cervical cancer tissues and cells. Further, MAGL inhibition suppressed the growth of cervical cancer cells in vitro and in vivo. In addition, apoptosis and G1‐phase cell cycle arrest were induced by MAGL knockdown. MAGL silencing‐mediated upregulation of Bax and cleaved caspase‐3, and downregulation of Bcl‐2 was responsible for triggering apoptosis. More importantly, the migration and invasion of cervical cancer cells were restrained by MAGL depletion.ConclusionsMAGL drives the progression of cervical cancer, which can be a promising candidate to identify effective therapy for cervical cancer.

A comparison of high‐risk human papillomavirus DNA detection between urine and cervical sample testing in women with abnormal Pap smears

AbstractAimsTo compare the clinical performance of high‐risk human papillomavirus (hrHPV) DNA detection between urine and cervical samples collected from the same patient for the detection of CIN2+ lesions (high‐grade squamous intraepithelial lesions or cervical cancer lesions). The secondary objectives were to evaluate agreement among hrHPV genotypes and to compare patient satisfaction between urine and cervical sample collection.MethodsThis prospective cross‐sectional study enrolled 96 women with abnormal cervical cytology who attended the colposcopy clinic at Siriraj Hospital (Bangkok, Thailand) between July 2016 and January 2017. Self‐collected random‐voiding and first stream urine samples were collected into a universal sterile urine container and immediately mixing with preservative before the pelvic examination. Cervical tissue sampling was performed according to standard treatment guidelines. Both specimens were sent for extraction and detection of hrHPV by Anyplex II HPV high‐risk testing. Study patients were surveyed to compare patient satisfaction between urine and cervical sample collection.ResultsCarcinogenic hrHPV positive rate was 73% in urine samples and 81% in cervical samples. The sensitivity for HPV in the detection CIN2+ was high in both the urine and cervical groups at 86.2% and 94.8%, respectively. Agreement between the urine and cervical groups for HPV 16 or 18 detection was high, with kappa values of 0.86 for subtypes 16/18. Urine specimen collection had significantly higher satisfaction and acceptability than cervical specimen collection.ConclusionUrine hrHPV testing by real‐time polymerase chain reaction demonstrated high sensitivity and accuracy for the detection of CIN2+ lesions, with very good agreement when compared with cervical sample testing.

Comparative performance of various human papillomavirus assays available in Korea for detecting cervical intraepithelial neoplasia

AbstractAimThe aim of this study was to evaluate the clinical performance for detecting cervical intraepithelial neoplasia (CIN) 2 or higher lesions among available human papillomavirus infection (HPV) genotyping tests in Korea.MethodsEligible patients visited 13 tertiary hospitals for colposcopic biopsy following cervical cytology and HPV genotyping test between January and December 2018. Baseline characteristics including age, body mass index (BMI), and parity were collected from 3798 patients. The performance of the Roche Cobas HPV 4800 was evaluated against other domestic HPV assays to detect CIN2 or higher.ResultsA total of seven types of HPV genotyping tests were analyzed in the research institutes. A total of 1358 patients (35.8%) tested Anyplex II HPV 28 and 701 patients (18.5%) tested Cobas 4800 HPV. The overall sensitivity in the detection of CIN2 or higher was 41.5% (38.9–44.1) in patients positive for HPV 16/18.The Cobas test for HPV 16/18 was concordant with other assays evaluated for detection of CIN2 or higher and showed sensitivity of 46.6%, which was not significantly different from other assays. Although Anyplex II HPV28 (Seegene) showed slightly decreased sensitivity for detecting CIN2 or higher lesion with HPV 16/18 positive (39.8%, p < 0.05) compared to Cobas 4800, in aspect of high‐risk HPV positive, Anyplex II HPV28 showed increased sensitivity (96.9%, p < 0.05).ConclusionThe performance of the HPV genotype test that were commonly used in Korea was concordant with Cobas HPV test. Further studies are needed to evaluate the safety, efficiency, and cost‐effectiveness of the various commercially available domestic HPV assays.

The prognosis of “sandwich” mode of postoperative chemotherapy and radiation in patients with locally advanced cervical cancer

AbstractObjectiveThis study aims to evaluate the survival outcome between different postoperative radiation and chemotherapy modes in locally advanced cervical cancer (LACC).MethodsThis study is a retrospective cohort study. A total of 150 patients with LACC underwent radical hysterectomy combined with postoperative radiation and /or chemotherapy from October 2009 to October 2019. Of those, 101 patients who received “sandwich” adjuvant chemotherapy and radiation (SCR) were enrolled into group A and 49 patients who received simple radiation were enrolled into group B. The primary outcome was the rates of progression‐free survival (PFS) and overall survival (OS).ResultsOf 150 patients, 95.3% (143/150) patients complete the study. The rates of deep myometrial invasion (92% and 72.9%, p = 0.007), lymph vascular invasion positive (74.3% and 26.5%, p = 2.59 × 10−8), positive surgical margin (11.9% and 0%, p = 0.012), and lymph‐node involvement (40.6% vs. 4.1%, p = 4.0 × 10−6) at baseline were higher in the group A than group B. There was no difference between the follow‐up time of group A and group B (45.81 ± 16.83 vs. 45.81 ± 16.84 months, p = 0.665). After the postoperative adjuvant, group A achieved the comparable PFS to group B [p = 0.40; hazard ratio (HR), 1.45; 95% CI, 0.62–3.38]. The cumulative rate of OS in group A was comparable in group B (p = 0.31; HR, 1.53; 95% CI, 0.68–3.45).ConclusionsPostoperative ‘sandwich’ chemotherapy and radiation could yield a similar survival rate to radiation alone in LACC women with high‐risk factors such as deep interstitial infiltration, lymphatic vascular space infiltration, positive resection margin, and lymph‐node metastasis.

Visual inspection with acetic acid screening for cervical cancer among women receiving anti‐retroviral therapy for human immunodeficiency virus infection in northern Tanzania

AbstractAimTo evaluate visual inspection with acetic acid (VIA) screening for cervical cancer among human immunodeficiency virus (HIV)‐positive patients in an East African community.MethodsDuring a July 2018 cervical cancer screen‐and‐treat in Mwanza, Tanzania, participants were offered free cervical VIA screening, cryotherapy when indicated, and HIV testing. Acetowhite lesions and/or abnormal vascularity were designated VIA positive in accordance with current guidelines. The association between VIA results and HIV status was compared using Chi‐square and Fisher exact tests.ResultsEight hundred and twenty‐four of 921 consented participants underwent VIA screening and 25.0% (n = 206) were VIA positive. VIA‐positive nonpregnant women (n = 147) received cryotherapy and 15 (1.8%) with cancerous‐appearing lesions were referred to Bugando Hospital. Sixty‐six women were HIV‐positive and included 25 diagnosed with HIV at the cervical cancer VIA screening and 41 with a prior diagnosis of HIV who were receiving antiretroviral therapy (ART) at the time of cervical cancer VIA screening. Sixty‐four of these 66 patients, were screened with VIA. HIV infection was not associated with VIA findings. Abnormal VIA positive screening was observed in 20.3% (n = 13) of HIV‐positive patients and in 24.4% (n = 145) of HIV‐negative patients (p = 0.508). A nonsignificant trend of higher VIA positive screens among newly diagnosed HIV patients of 26.1% (n = 6) versus patients with preexisting HIV on ART of 17.1% (n = 7) was observed (p = 0.580).ConclusionThe unexpected lack of correlation between HIV infection and VIA positivity in a community with access to ART warrants additional research regarding the previously described role of ART in attenuating HPV‐mediated neoplasia.

Association between inflammatory bowel disease and risk of abnormalities of uterine cervix

AbstractBackgroundPrevious studies provided inconsistent results regarding the association between inflammatory bowel disease (IBD) and risk of abnormalities of uterine cervix. The study aimed to make a meta‐analysis to evaluate the association between IBD and risk of abnormalities of uterine cervix.MethodsArticles published until April 2021 and regarding the association between IBD and risk of abnormalities of uterine cervix were searched in the following databases: PubMed, Web of Science, EMBASE, Medline, and Google Scholar. Odds ratios (ORs) from case–control studies and relative risks (RRs) from cohort studies with their 95% confidence intervals (CIs) were computed to generate a pooled effect size and 95% CI using STATA 12.0 software.ResultsThe present study finally included seven cohort studies (including 94 144 IBD patients and 53 661 004 HC) and four case–control studies (including 20 267 cases and 60 034 matched controls). The meta‐analysis indicated a positive association between IBD and risk of abnormalities of uterine cervix with a random‐effects model (OR/RR = 2.46, 95% CI 1.55–3.91, I2 = 91.8%, p < 0.001). However, no significant association between IBD and risk of cervical cancer was showed in the study with a random‐effects model (OR/RR = 1.54, 95% CI 0.83–2.85, I2 = 82.2%, p < 0.001).ConclusionIn conclusion, IBD is associated with a 146% higher risk of abnormalities of uterine cervix. However, the study demonstrated no significant association between IBD and risk of cervical cancer. Thus, a conventional screening for abnormalities of uterine cervix is essential for IBD patients.

The influence process of sarcopenia on female cancer: A systematic review and meta‐analysis

AbstractBackgroundSarcopenia is one of the early pathological manifestations of cancer cachexia. This change in quality and function has a general and special impact on the prognosis of many types of tumors. However, there are few studies to evaluate the overall impact of sarcopenia on the prognosis of gynecological tumors in sufficient follow‐up period.MethodsThis study systematically searched PubMed, EMBASE, web of science, and MEDLINE databases for related studies and related references since April 15, 2021. The 1‐year, 5‐year overall survival (OS), progression‐free survival (PFS), hazard ratio (HR), and 95% confidence interval (CI) were analyzed by Stata 14.0.(CRD 42021236036).ResultsA total of 23 observational studies involving 3495 female patients were included in the analysis, with an average prevalence of 46.9% (38.5%–55.3%). Meta‐analysis showed that the 1‐year OS (RR: 1.60, 95% CI = [1.04, 2.46]) of patients with sarcopenia was significantly lower than that of patients without sarcopenia, and then this effect gradually decreased. The results showed that sarcopenia was an independent predictor of OS (HR: 1.78, 95% CI = [1.38, 2.30]) and PFS (HR: 1.32, 95% CI = [1.02, 1.70]) in gynecological cancer patients. Subgroup analysis showed that sarcopenia was significant in Asian population (HR: 1.93, 95% CI = [1.18, 3.17]) and cervical cancer patients (HR: 5.07, 95% CI = [2.82, 9.56]).ConclusionThe survival and recurrence outcome of patients with sarcopenia independently related to surgery, and its impact is very obvious in the short term. In addition, Asian participants with sarcopenia face a greater risk of death than Western participants.

Crizotinib‐induced anti‐cancer activity in human cervical carcinoma cells via ROS‐dependent mitochondrial depolarization and induction of apoptotic pathway

AbstractIntroductionCervical cancer is one of the leading causes of mortality among women population worldwide. In spite of recurrent screening, vaccination, and chemotherapeutic interventions, combating cervical cancer still remains a challenge. Crizotinib is a small molecule inhibitor that targets mesenchymal epithelial transition factor (c‐MET) and has been successfully studied for its anti‐cancer effects in non‐small cell lung cancer, pancreatic, gastric, renal, prostate, and breast carcinomas. Although c‐MET is a well‐known prognostic, diagnostic, and therapeutic target in cervical cancer, anti‐cancer properties of its inhibitor crizotinib against cervical carcinoma, has not been explored yet.MethodsIn the present study, the anti‐cancer effects of crizotinib on cervical cancer cells were evaluated using various in vitro cell‐based assays, such as labelling drug‐treated cells with MTT, H2DCFDA, Annexin V5‐fluorescein isothiocyanate (FITC) antibody, JC‐1, PI, and analysis using fluorescence‐activated cell sorting (FACS).ResultsThe molecule was found to effectively inhibit proliferation of cervical cancer cells HeLa and SiHa with an IC50 of 0.641 ± 0.0724 and 0.871 ± 0.104 μM, respectively, and induce apoptosis in a dose‐dependent manner. Further investigations showed that crizotinib‐induced production of reactive oxygen species (ROS) with increasing concentrations further resulted in mitochondrial membrane depolarization. However, the drug had no effect on cell cycle progression of HeLa and SiHa cells.ConclusionThus, the study elucidates the cytotoxic effects of crizotinib in cervical cancer cells by activation of ROS‐dependent apoptotic pathway via mitochondrial depolarization. These findings will further aid the evaluation of other molecular mechanisms of crizotinib and would pave the way for its implication as a chemotherapeutic option in cervical cancer.

Downregulation of GTSE1 leads to the inhibition of proliferation, migration, and Warburg effect in cervical cancer by blocking LHDA expression

AbstractAimG2 and S phase‐expressed‐1 (GTSE1) has been identified to play a vital role in several kinds of cancers, but its role in cervical cancer development remains unknown. Herein, we aimed to reveal the role and underlying mechanism of GTSE1 in cervical cancer cell growth, migration, and aerobic glycolysis.MethodsGTSE1 expression levels in cervical cancer tissues and normal cervical tissues were determined by real time PCR and immunohistochemistry. Human short hairpin RNA was used to downregulate GTSE1 level in cervical cancer cells SiHa and HeLa cells. Colony formation, cell counting kit‐8, and wound‐healing assays were used for cell function evaluation. Lactate production, lactate dehydrogenase activity, and glucose concentration were tested to assess the Warburg effect.ResultsGTSE1 expressions at both mRNA and protein levels were significantly elevated in cervical cancer tissues compared with normal tissues. Downregulation of GTSE1 induced significant repressions in cell colony formation, viability and migration, and Warburg effect, as well as reduced expression of lactate dehydrogenase isoform A (LDHA) at mRNA and protein levels. Additionally, downregulation of GTSE1 weakened the tumorigenesis of HeLa and SiHa cells in vivo.ConclusionThis study demonstrated that downregulation of GTSE1 led to significant inhibitions in cell proliferation, migration, tumorigenesis, and Warburg effect in cervical cancer by blocking the expression of LHDA.

Laparoscopic retroperitoneal para‐aortic lymph node biopsy in advanced cervical cancer with pelvic lymph node metastases: A single‐center prospective study

Abstract Aim Extended‐field concurrent chemoradiation therapy (Ex‐CCRT) has been widely used for para‐aortic lymph node (PAN) metastases confirmed by radiographic assessment without surgical exploration. The objective of this prospective study was to evaluate the clinical value of laparoscopic retroperitoneal PAN biopsy in locally advanced cervical cancer (LACC) with pelvic lymph node (PLN) metastases. Methods From May 2017 to March 2020, stage IIB–IIIB cervical cancer patients who were diagnosed with PLN metastasis using positron emission tomography‐computed tomography (PET‐CT) with maximum standardized uptake value (SUVmax) ≥2.0 underwent laparoscopic retroperitoneal PAN biopsy. The radiation fields were extended to PAN areas with pathological metastases. Results Fourteen patients were diagnosed with cervical squamous cell carcinoma of the International Federation of Gynecology and Obstetrics (FIGO) stage IIB ( n  = 7) and IIIB ( n  = 7). The median operating time was 138 min (range, 104–184 min). The median number of harvested PANs was 19 (range, 6–36). Three patients were positive for PAN metastasis on histological analysis. In this study, the sensitivity and specificity of PET‐CT were 66.7% and 90.9%, respectively. Conclusion Our study is characterized by the use of more appropriate eligibility criteria for LACC with PLN metastases. Our results revealed that laparoscopic retroperitoneal PAN biopsy may be a useful approach to determine the radiation field for PANs during standard radiotherapy planning.

Lymphoepithelioma‐like carcinoma of uterine cervix: Preoperative diagnosis and course in three cases

AbstractLymphoepithelioma‐like carcinoma of the uterine cervix is a rare variant of squamous cell carcinoma. Herein, we describe three cases of lymphoepithelioma‐like carcinoma of the uterine cervix and review relevant literature. All three patients initially presented with postmenopausal bleeding. Gross appearances were endophytic with ulcerated mucosa in case 1, exophytic with polypoid morphology in case 2, and unremarkable even using colposcopy and hysteroscopy in case 3. Magnetic resonance imaging demonstrated well‐demarcated cervical masses with high‐intermediate intensity on T2‐weighted images and high intensity on diffusion‐weighted images in all three cases. In case 3, biopsy referring to local information from magnetic resonance images was required for preoperative diagnosis. We reviewed the literature of 59 lymphoepithelioma‐like carcinoma cases in 19 papers published between 2001 and 2020. Preoperative diagnosis of lymphoepithelioma‐like carcinoma is sometimes challenging, although magnetic resonance imaging findings may help determine the location of the tumor and obtain a successful biopsy.

Recurrence pattern and prognostic factors for survival in cervical cancer with lymph node metastasis

AbstractAimThe aim of this study is to evaluate the recurrence pattern and oncological outcomes in cervical cancer (CC) patients with lymph node metastasis.MethodsThis study included 224 International Federation of Gynecology and Obstetrics (FIGO) 2009 stage IB1‐IIIB CC patients with pathologically proven lymph node metastasis. Surgical intervention was grouped as hysterectomy performed/not performed. Adjuvant therapy decision was made by the tumor board. Radiotherapy was applied to all patients with lymph node metastasis.ResultsOnly paraaortic lymph node metastasis was determined as an independent prognostic factor for recurrence. Presence of paraaortic lymph node metastasis increased the risk of recurrence more than two times (odds ratio: 2.129; 95% confidence interval: 1.011–4.485; p = 0.047). An independent prognostic factor for death because of disease was age only. Risk of death was nearly doubled with younger age (odds ratio: 2.693; 95% confidence interval: 1.064–6.184; p = 0.037).ConclusionThe most of recurrences were located at distant sites and multiple regions. Paraaortic lymph node metastasis was the only independent prognostic factor for recurrence, in spite of that age was an independent predictor for risk of death in patients with early stage or locally advanced CC and also with surgically proven metastatic lymph nodes. Furthermore, the presence of the paraaortic lymph node metastasis was significantly associated with distant recurrence. Therefore, more appropriate and individualized therapy strategy focusing on intenser systemic chemotherapy options in addition to radiotherapy should be taken into consideration according to paraaortic lymph node metastasis and age.

Diagnostic performance of HPV E6/E7 mRNA testing towards HPV‐DNA testing and p16/Ki67 immunostaining as a biomarker of high‐risk HPV recurrence in Greek women surgically treated for their cervical lesions

AbstractAimTo evaluate the diagnostic performance of E6/E7 HPV‐mRNA overexpression towards HPV‐DNA testing and p16/Ki67 immunocytochemistry in a post‐op population to verify if this biomarker can be effectively used as indicator of successful cervical intraepithelial neoplasia (CIN) treatment.MethodsOur study retrospectively analyzed 197 patients of our Colposcopy Clinic between January 2013 and September 2020 coming with an abnormal Pap smear suggestive for colposcopy, and after a series of follow‐ups including liquid‐based cytology (LBC) and punch‐biopsy sampling, there were surgically treated. LBC was used for cytology and molecular analysis of the three HPV‐related biomarkers.ResultsSix months after treatment, 93% of the HPV‐mRNA‐positive women became negative while this applied to only 80.2% of the HPV‐DNA‐positive women. HPV persistence was 6.9% at 6–12 months after treatment. The comparison among cytology, colposcopy, HPV‐DNA test, and HPV‐mRNA test after treatment revealed that the last one is the only with a strong correlation with actual severity (histology during treatment) (ρ = 0.345, p = 0.006) implying that clinical cases with more severe CIN may have higher chances of unsuccessful treatment. HPV‐mRNA test had higher sensitivity (100%), specificity (96.88%), and positive predictive value (45.45%) for CIN2+ recurrent lesions when compared with HPV‐DNA testing (80%, 82.81%, 10.81% respectively) and p16/Ki67 immunocytochemistry (80%, 95.83%, 33.33% respectively) while their negative predictive values were similar.ConclusionsE6/E7 mRNA detection has higher diagnostic values for the prediction of treatment failure compared with HPV‐DNA testing and p16/Ki67 immunocytochemistry, and as an outcome could be used as predictive indicator of CIN‐treatment status.

Diagnostic Use of the Combination of CA72 ‐4 and Tumor Volume in Mucinous Ovarian Tumors

ABSTRACT Objective Mucinous ovarian cancer (MOC) is a rare epithelial ovarian cancer subtype with poor prognosis, particularly in advanced stages. Differentiating MOC from mucinous borderline ovarian tumor (MBT) remains clinically challenging, often leading to delayed or inadequate treatment. Accurate preoperative diagnosis is crucial for guiding surgical strategies and improving patient outcomes. This study evaluated preoperative clinical factors that can distinguish MOC from MBT. Methods We retrospectively analyzed 46 ovarian mucinous tumors diagnosed between 2017 and 2021, including 15 MOC and 31 MBT cases confirmed by histopathology. Patient age, tumor laterality, tumor size, tumor markers (CA125, CA19‐9, CA72‐4, CEA), and tumor volume were assessed. Tumor size was measured as the maximum magnetic resonance imaging diameter, whereas volume was calculated using three‐dimensional imaging. Statistical analyses included the Mann–Whitney U test and receiver operating characteristic curve analysis, with AUC as a measure of diagnostic accuracy. Results Among the tumor markers, CA72‐4 exhibited the highest diagnostic accuracy (area under the curve [AUC]: 0.834), with significantly higher levels in MOC than in MBT ( p  < 0.001). Tumor size alone was an unreliable discriminator (AUC: 0.42). The tumor volume tended to be larger in MBT than in MOC (median: 2 362 878 cm 3 vs. 1 262 436 cm 3 ; p  = 0.77). However, the combination of CA72‐4 and tumor volume improved the diagnostic performance (AUC: 0.875). Conclusion The combination of CA72‐4 levels and tumor volume enhances preoperative differentiation between MOC and MBT. This combined approach may optimize surgical planning and improve patient outcomes.

Identification and construction of a prognostic risk model based on multi‐RNA methylation regulators in cervical cancer

AbstractAimCervical cancer is one of the most aggressive female cancers. RNA methylation is a necessary epigenetic modification in biological process. This study aimed to construct an RNA methylation regulator‐based risk model for predicting the prognosis of cervical cancer patients.MethodsThe transcriptome profiles of cervical cancer data were obtained from The Cancer Genome Atlas (TCGA) and GSE44001. An RNA methylation‐related risk model was constructed and assessed by the Least absolute shrinkage and selection operator (Lasso)‐penalized Cox regression model and receiver operating characteristic (ROC). Kaplan–Meier and Cox regression analyses were used to evaluate the prognostic effect of the risk model and calculated scores. The immune infiltration difference was further analyzed between the subgroups with a single‐sample gene set enrichment analysis (ssGSEA).ResultsA total of 63 methylation modulators were included in this study, and 618 cervical cancer patients were identified from TCGA and GSE44001. Differential expression genes profiling RNA methylation regulators between normal and tumor samples were distinct. A four‐gene signature panel was constructed to predict the prognostic risk. The predictive ability was satisfactory. Cervical cancer patients were classified into high‐ or low‐risk subgroups according to the median risk score. Moreover, the immune infiltration patterns between them differed.ConclusionsA risk model including four RNA methylation regulators was constructed, which will provide new perspectives for further investigation of the relationship between RNA methylation and cervical cancer.

Oncologic outcome in patients with 2018 FIGO stage IB cervical cancer: Is tumor size important?

AbstractBackgroundTo evaluate the prognostic factors and oncologic outcome in patients with 2018 International Federation of Gynecology and Obstetrics (FIGO) stage IB cervical cancer (CC) after radical hysterectomy and lymphadenectomy.Materials and MethodsThis study included 290 patients with type II or III radical hysterectomy + pelvic ± para‐aortic lymphadenectomy and 2018 FIGO stage IB1‐3 epithelial CC. Disease‐free survival (DFS) estimates were determinate by using the Kaplan–Meier method. Survival curves were compared using the log‐rank test. Multivariate analysis was performed using a Cox proportional hazards models.ResultsThe mean age of study cohort was 52 ± 10.25 years. Five‐year DFS was 93% in entire cohort. On univariate analysis, surgical border involvement (p = 0.007), lymphovascular space invasion (LVSI) (p = 0.040), uterine involvement (p = 0.040), and depth of cervical stromal invasion (p = 0.007) were found to have statistical significance for DFS. However, none of them were independent prognostic factors for the risk of recurrence. Tumor size according to 2018 FIGO staging criteria was not related with recurrence.ConclusionsSurgical border involvement, LVSI, depth of cervical stromal invasion, and uterine involvement were predictors for DFS on univariate analysis. Tumor size was not predicting to recurrence in patient with 2018 FIGO stage IB1‐3 CC.

Impact of lymphadenectomy in patients with locally recurrent or persistent cervical cancer treated with salvage hysterectomy

AbstractAimTo investigate the role of lymphadenectomy (LND) in locally recurrent or persistent cervical cancer patients treated with salvage hysterectomy.MethodsLocally recurrent or persistent cervical cancer patients treated with salvage hysterectomy, with or without LND, were identified. Patients were divided into two groups according to the status of radiologic evidence of lymph node metastasis, and the impact of LND was investigated by evaluating postoperative survival.ResultsThis study included 72 patients; 48 did not show radiological evidence of lymph node metastasis (Group 1) while 24 did (Group 2). Overall, the addition of LND to salvage hysterectomy resulted in increased postoperative complications. In Group 1, salvage hysterectomy plus LND resulted in the identification of five cases with false‐negative lymph nodes (19.2%), but showed no advantage over salvage hysterectomy alone in terms of postoperative survival. In Group 2, all patients underwent LND, which resulted in the identification of eight cases with false‐positive nodes (33.3%), and reasonably long postoperative survival. The estimated 3‐year postoperative survival rate in this group was 39.7%.ConclusionIncluding LND in salvage hysterectomy allows for precise lymph node staging but increases risk of postoperative complications. However, considering the inability to improve survival, LND should not be performed during salvage hysterectomy in patients without radiological evidence of lymph node metastasis. In patients with radiological evidence of lymph node metastasis, salvage hysterectomy plus LND can only be performed in those who understand the risk of postoperative complications and the limited evidence supporting its survival advantage.

Overview of laparoscopic surgery for cervical cancer in Japan: Updates after the laparoscopic approach to cervical cancer trial

AbstractLaparoscopic radical hysterectomy (LRH) for cervical cancer has been reported to be similar oncologic outcome compared to abdominal radical hysterectomy (ARH) in many retrospective studies. In Japan, LRH has been covered by insurance since April 2018. In 2018, the same year that LRH became covered by insurance, Ramirez et al. at MD Anderson Cancer Center reported the results of a large phase III laparoscopic approach to cervical cancer trial (LACC trial) on the prognosis of open versus laparoscopic/robot‐assisted minimally invasive radical hysterectomy. The results showed that minimally invasive approaches were associated with a higher rate of recurrence and death. At this point, it is not clear what is wrong with LRH and why it has a poorer prognosis compared to ARH. In this report, after the LACC report, we would like to review the current status of minimally invasive surgery for cervical cancer and future directions.

Construction of a diagnostic classifier for cervical intraepithelial neoplasia and cervical cancer based on XGBoost feature selection and random forest model

AbstractBackgroundThe pathological phenotype of early‐stage cervical cancer (CC) is similar to that of cervical intraepithelial neoplasia (CIN), which provides a challenge for the diagnosis of cervical precancerous lesions. Meanwhile, the existing diagnostic methods have certain subjectivity and limitations, resulting in the possibility of misdiagnosis or missed diagnosis. Hence, some methods are needed to assist diagnosis of CC and CIN.MethodsBased on the data of CIN and CC in gene expression omnibus (GEO) dataset, the eXtreme Gradient Boosting (XGBoost) algorithm was used to screen the feature genes between CIN and CC for constructing the classifier. Incremental feature selection (IFS) curve was also used for screening. The classifier was validated for reliability using principal component analysis (PCA) dimensionality reduction analysis and heat map analysis of gene expression. Then, differentially expressed genes of CIN and CC were intersected with the classifier genes. Genes in the intersection were used as seeds for protein–protein interaction network construction and restart random walk analysis. And the genes with the top 50 affinity coefficients were selected for gene ontology (GO) and kyoto encyclopedia of genes and genome (KEGG) enrichment analyses to observe the biological functions with differences between CIN and CC.ResultsThe peripheral blood genes of CIN and CC were analyzed, and seven genes were screened. Using this gene for classifier construction, IFS curve screening revealed that the three‐feature gene classifier constructed according to the random forest model had the best effect. The results of PCA dimensionality reduction analysis and gene expression heat map analysis showed that the three‐gene classifier could effectively distinguish CIN from CC.ConclusionA three‐gene diagnostic classifier can effectively distinguish CIN patients from CC patients and provide a reference for the clinical diagnosis of early CC.

Identification of novel genetic and epigenetic regulators of different tissue types of cervical cancer

AbstractObjectivesThe study aimed to find differential gene mutations, DNA methylation, and expression profiles among different categories of cervical cancer samples.MethodsThe study was based on freely available gene mutations, promoter methylation, and gene expression status of The Cancer Genome Atlas (TCGA) cervical cancer samples and adjacent normal tissues in the Genomic Data Commons (GDC) portal. The association of CpG island methylation with gene expression was determined through negative correlation analysis.ResultsWe identified that the ErbB signaling pathway and proteoglycans pathway was significantly associated with adenocarcinoma cervical cancers patients. In these pathways, missense mutation especially S310F in theERBB2gene as well as G12D and A146T in theKRASgene were significantly associated with adenocarcinoma cases. Furthermore, a comparison of SCC cases with adjacent control tissues revealed differential hypermethylation of two CpG positions of theKAAG1gene and differential downregulation ofNPY1RandNPY5Rgenes in cervical squamous cell carcinoma compared to cervical adenocarcinoma cases and adjacent normal tissues. Specifically, the hypermethylation of the promoter region of theKAAG1gene might be responsible for the carcinogenesis of cervical squamous cells exclusively and methylation marks can be reversible by the widely used drug, azacytidine. In contrast, adenocarcinoma cervical cancer cases may be treated with floxuridine which is successfully utilized for other tissue‐specific adenocarcinoma cases.ConclusionsThese results provide valuable insight into the differential molecular markers among the categories of cervical cancer, which helps our ability to classify these cancers and for targeted therapy.

Patterns and predictors of site‐specific recurrence in cervical cancer after radical hysterectomy

AbstractAimThis study examines patterns and predictors of site‐specific recurrence to explore the causes of local recurrence of cervical cancer.MethodsRadical hysterectomy was performed in 121 patients (stage IB–IIB). Nerve‐sparing was performed whenever possible. The first recurrence in local, regional, and distant areas was examined. We investigated the possibility of nerve involvement in local recurrence, focusing on paravaginal tissues containing the pelvic plexus. We provide Supporting Information on local recurrence in the paravaginal area.ResultsLocal recurrence was an independent event from regional or distant recurrence. Local recurrence was seen only in high‐risk patients, while regional and distant recurrences were not or less related to the risk category. The independent risk factors by logistic regression for local, regional, and distant recurrence were parametrial invasion, vaginal invasion, and lymph node metastasis, respectively. Local recurrence showed a comparable or more significant negative impact on survival than distant recurrence. Among seven patients with local recurrences, five had a recurrence in the paravagina. The rate of paravaginal recurrence was one in 76 early‐stage and four in 45 locally advanced diseases. Four sites of paravaginal recurrence occurred on the nerve‐sparing side and two on the non‐nerve‐sparing side. Supporting Information demonstrated histological evidence of perineural spread into the pelvic plexus and perineural invasion of the primary tumor.ConclusionsA high percentage of local recurrences are in paravaginal tissue containing the pelvic plexus. The causal association of nerve‐sparing surgery and perineural invasion with local recurrence needs to be investigated in large prospective studies.

Biology and management of lobular endocervical glandular hyperplasia

AbstractAimLobular endocervical glandular hyperplasia (LEGH) is a multicystic proliferative disorder of the uterine cervix. The aim of this review was to clarify the current understanding of this unique tumor.MethodThis article reviews the chronological progress of research regarding clinico‐pathological and genetic aspects of LEGH and related cervical cystic diseases such as Nabothian cyst and adenocarcinoma of gastric type (GAS), using the literature and data from our institute. We also describe clinical management including preoperative diagnosis and adequate surgical/expectant treatment based on the biological features.ResultsRecent studies revealed several unique aspects of LEGH, that is, (i) production of gastric mucin, (ii) symptomatic and histological similarity with minimal deviation adenocarcinoma (MDA), and (iii) frequent association with GAS, including MDA. These findings indicated that LEGH is a gastric metaplasia, as well as pre‐cancerous neoplasia. For the preoperative diagnosis of LEGH, the combination of “cosmos” sign on magnetic resonance imaging, detection of gastric mucin, and lack of nuclear atypia on cytology is important. Cone biopsy is effective for pathological diagnosis. Simple hysterectomy is indicated as surgical treatment for LEGH; however, meticulous follow‐up is also an option, especially for young patients, because the rate of malignant transformation was reported to be 1%–2%. For LEGH patients who selected follow‐up, a worsening cytology and increase in lesion size were important signs of malignant change of LEGH for safe follow‐up.ConclusionProper understanding of the characteristics of LEGH is important for adequate management.

LncRNA LAMTOR5‐AS1 sponges miR‐210‐3p and regulates cervical cancer progression

AbstractAimCervical cancer has attracted increasing attention in recent years, and the incidence has shown a trend of younger age. Therefore, it is an effective method to regulate the progression of cervical cancer through new prognostic biomarkers. The purpose of this study was to evaluate the potential of lncRNA LAMTOR5‐AS1 (LAMTOR5‐AS1) as a prognostic biomarker and reveal its regulatory role in cervical cancer.MethodsA total of 120 patients with cervical cancer were selected as research subjects to verify the prognostic effect of LAMTOR5‐AS1 in a series of experiments. The expression of LAMTOR5‐AS1 in cervical cancer tissues and cells was determined by polymerase chain reaction assay. The proliferation, migration, and invasion ability of cervical cancer cells were evaluated by Cell Counting Kit‐8 (CCK‐8) and Transwell assay. Luciferase reporter gene detection was used to determine the mechanism of LAMTOR5‐AS1 targeting miR‐210‐3p, and to reflect the prognostic value of LAMTOR5‐AS1 according to statistical methods.ResultsLAMTOR5‐AS1 decreased in cervical cancer tissues, while miR‐210‐3p expression increased. In the study of cervical cancer cells, it was found that the LAMTOR5‐AS1 sponge miR‐210‐3p was associated with the malignant progression of cervical cancer. Overexpression of LAMTOR5‐AS1 could effectively inhibit the development of cervical cancer cells and might be chosen as a prognostic biomarker of cervical cancer.ConclusionsLAMTOR5‐AS1 sponges miR‐210‐3p and modulates the progression of cervical cancer, which predict the prognosis of cervical cancer patients.

Cerclage in surgically shortened uterine cervix and pregnancy outcome: A retrospective comparison between the abdominal and vaginal procedures

AbstractBackgroundCerclage for uterine cervical incompetence can be performed by the transabdominal or transvaginal approach. Transabdominal cerclage (TAC) is indicated for women with a short cervix or a cervical laceration who are inapplicable to transvaginal cerclage (TVC). The larger the volume of tissue removed in cervical conization, the greater the rate of miscarriage or preterm delivery in the subsequent pregnancy.AimsThe aim of this study was to compare TAC and TVC in post‐cervical conization pregnancies.MethodsA retrospective, two‐group, comparative study was conducted involving subjects who underwent cervical cerclage (TAC, n = 14; TVC, n = 18) following cervical conization and who were cared for at the University of Miyazaki Hospital between 2008 and 2020. We compared study subject characteristics and outcomes between the two groups. Primary outcome was incidence of preterm labor <37 weeks of gestation between the two groups.ResultsThe preoperative median cervical length was significantly shorter in the TAC group (20.0 mm) than in the TVC group (31.0 mm; p < 0.01). Preoperative vaginal discharge cultures positive for Gardnerella showed a tendency to be greater in the TAC group (p = 0.073). There was no significant difference in the preterm delivery rate < 37 weeks of gestation between TAC (1/14, 7.1%) and TVC (6/18, 33.3%) groups, p = 0.10. Noninferiority test using multiple regression analysis showed that TAC is not inferior to TVC regarding gestational age at delivery, even though cervical length of TAC was significantly shorter.ConclusionWomen who were inapplicable to TVC due to a short cervix still achieved an equivalent outcome with TAC.

Safety and efficacy of a modified technique of laparoscopic radical hysterectomy for cervical cancer

AbstractAimObjective to investigate the feasibility, safety, and short‐term efficacy of laparoscopic radical hysterectomy without uterine lifter combined with self‐locking nylon band.MethodsThe clinical data of 152 patients who underwent a laparoscopic radical hysterectomy in the Department of gynecology and oncology of Changzhou maternal and child health hospital from January 2017 to June 2020 were analyzed retrospectively, including 97 patients who used uterine lifter (traditional laparoscopic radical hysterectomy) and 55 patients who underwent operation without uterine lifter but combining with self‐locking nylon band (modified laparoscopic radical hysterectomy). The differences in operation time, intraoperative blood loss, the width of excised parauterine tissue, the length of the excised vaginal wall, postoperative pathology and short‐term prognosis between the two groups were compared and analyzed.ResultsThere were no significant differences between the two groups in operation time, intraoperative blood loss, the width of parauterine tissue, and the length of the vaginal wall (p > 0.05). There were no significant differences in the number of lymph nodes, pelvic lymph node metastasis rate and depth of cervical interstitial infiltration between the two groups (p > 0.05), the infiltration rate of lymphatic vascular space in the traditional group was higher than that in the improved group (p < 0.05).ConclusionIt is feasible and safe for laparoscopic radical hysterectomy without uterine lifter combining with a self‐locking nylon band to seal the vaginal wall. The uterine lifter may lead to lymphatic vascular space infiltration of tumor cells.

Postsurgical urodynamic study of total laparoscopic nerve‐sparing radical hysterectomy for uterine cervical cancer

AbstractAimTo evaluate the impact on urodynamic results between the laparoscopic nerve‐sparing radical hysterectomy (LRH) following a step‐by‐step procedure and abdominal nerve‐sparing radical hysterectomy (ARH) for patients with uterine cervical cancer.MethodsThis retrospective study enrolled 76 patients with cervical cancer: 35 in the LRH group and 41 in the ARH group. We analyzed their postoperative bladder function in a urodynamics study and examined the volume of resected pelvic nerves contained in parametrial sections using S‐100 antibody staining.ResultsEstimated blood loss and hospital stay after operation for the LRH group were significantly better than those in the ARH group (p < 0.0001). As well, the number of harvested lymph nodes was significantly higher in the LRH group (p = 0.044). There was no difference in perioperative complications between the two groups in this study. The 5‐year disease‐free survival rates and overall survival rates were 91.2% and 94.0% in the LRH group and 87.8% and 95.1% in the ARH group, both respectively. Although the median residual urine volume were no statistical differences between the LRH group and the ARH group, the recovery of postoperative bladder function (uroflowmetry) in the LRH group rapidly reached presurgery levels at 1 month, and the LRH group had a smaller number of s‐100 antibody stained nerves contained the parametrial sections.ConclusionWe demonstrated that LRH following a step‐by‐step procedure could achieve a higher level of prevention of damage to the bladder branch of the pelvic splanchnic nerve plexus and thus restore bladder function more rapidly.

Attitudes towards prevention of cervical cancer and early diagnosis among female academicians

AbstractBackgroundIt is important for public health to determine the awareness of cervical cancer, which is preventable and treatable when detected at an early stage.AimThis study was conducted to determine female academicians' attitudes towards prevention and early diagnosis of cervical cancer and the factors affecting them.MethodsThis descriptive study was conducted with 211 female academicians working in all departments of a university. In the study, the data were collected using questionnaire form, the attitude scale for early diagnosis of cervical cancer, and the attitudes towards prevention of cervical cancer scale.ResultsIt was determined that 68.2% of the female academicians had knowledge about the pap smear test; however, 41.0% of them did not have the test because they could not find time, and 56.4% had the knowledge about the pap smear test from a healthcare professional. It was determined that academicians had lower scores from the Attitude Scale for Early Diagnosis of Cervical Cancer (88.55 ± 9.75) and above‐average scores from the Attitudes Towards Prevention of Cervical Cancer Scale (74.30 ± 15.92). It was found that area of expertise, income status, history of infectious disease, and vaginal douching affected both the early diagnosis of cervical cancer and the attitudes towards prevention of it.ConclusionThe female academicians inadequate attitudes towards early diagnosis of cervical cancer and better attitudes towards prevention. Nurses and administrators should encourage female academics and all women to screen for cervical cancer.

Prognostic value of lncRNA HOXA‐AS3 in cervical cancer by targeting miR‐29a‐3p and its regulatory effect on tumor progression

AbstractBackgroundWith the promotion of human papillomavirus (HPV) vaccine, cervical cancer has become a current research hotspot, and lncRNA has been confirmed to be used in the research of different diseases. This article systematically expounds the regulation and potential mechanisms of HOXA cluster antisense RNA 3 (HOXA‐AS3) in cervical cancer, and discusses its possibility as a prognostic biomarker for cervical cancer.MethodsRelative expression levels of HOXA‐AS3 and miR‐29a‐3p in tissues and cells were determined by real‐time quantitative polymerase chain reaction (RT‐qPCR). The survival of cervical cancer patients was analyzed by Kaplan–Meier method and the cumulative survival function table was drawn. The proliferation, migration, and invasion levels of HOXA‐AS3 in cells were detected according to cell counting kit‐8 (CCK‐8) and transwell method. The dual‐luciferase reporter gene assay confirmed the mechanism of action between HOXA‐AS3 and miR‐29a‐3p.ResultsHOXA‐AS3 was elevated and miR‐29a‐3p was decreased in tissues and cells of cervical cancer patients. Knockdown of HOXA‐AS3 could inhibit the progression of cervical cancer and was more conducive to patient survival. Bioinformatics analysis confirmed that HOXA‐AS3 negatively regulates cervical cancer development by sponging miR‐29a‐3p.ConclusionIn this research, knockdown of HOXA‐AS3 could alleviate the process of cervical cancer by sponging miR‐29a‐3p, suggesting that HOXA‐AS3 may be a potential prognostic target of cervical cancer, which could provide a theoretical basis for future clinical research of cervical cancer.

The role of vaginal microecology in the cervical cancer

AbstractAimTo explore the role of vaginal microecology in cervical cancer, so as to increase the understanding of cervical cancer and lay a foundation for future large‐sample clinical trials.MethodsWe reviewed and summarized the literature comprehensively, and discussed the relationship between vaginal microecology and HPV infection, CIN progression and cervical cancer, as well as the potential molecular mechanism and the prospects of probiotics and prebiotics in future cancer treatments.ResultsWith the popularization of high‐throughput sequencing technology and the development of bioinformatics analysis technology, many evidences show that the increase in the diversity of the bacterial community in the vaginal microecological environment and the decrease in the number of Lactobacilli are associated with the continuous infection of HPV and the further development of CIN, cervical cancer‐related.ConclusionsVaginal microecological imbalance has an important impact on the occurrence and development of cervical cancer. However, the pathogenesis is not completely clear, and more high‐level basic research and longitudinal clinical studies are needed to verify.

SPI1‐related protein inhibits cervical cancer cell progression and prevents macrophage cell migration

AbstractAimThe functions and molecular mechanisms of SPI1‐related protein (SPIB) were examined in cervical cancer (CC) cells.MethodsGenes related to miscarriage and prognosis in CC were identified by Kaplan–Meier and differential expression analysis, respectively. Cell proliferation, apoptosis, migration, and invasion were examined by cell counting kit‐8, flow cytometry, transwell migration, and transwell invasion assays, respectively. The potential functions and molecular mechanisms of SPIB in CC were speculated by gene set enrichment analysis (GSEA) analysis. The mRNA and protein levels of genes were examined by RT‐qPCR and western blot assays, respectively. The effect of SPIB on macrophage cells was tested by macrophage recruitment assay and bioinformatics analysis.ResultsA total of 753 dysregulated genes were identified in 88 TCGA CC samples with a history of one or more miscarriages versus 208 CC samples with no miscarriage history. Also, 91 genes related to CC prognosis were identified. SPIB, a gene related to both miscarriage and CC prognosis, inhibited Hela cell proliferation, migration, and invasion, and facilitated Hela cell apoptosis. GSEA analysis disclosed that SPIB might play vital roles in immunity, chemokine signaling pathway, and macrophage chemotaxis/activation in CC. Moreover, SPIB inhibited C‐X‐C motif chemokine ligand 8 (CXCL8), C‐C motif chemokine ligand 17 (CCL17), and C‐C motif chemokine ligand 25 (CCL25) expression in Hela cells, and SPIB overexpression in Hela cells hampered THP‐1 cell migration. Higher SPIB expression was associated with less M2 macrophage infiltration in CC.ConclusionsSPIB inhibited CC‐cell progression and hindered macrophage cell migration in CC.

Genetic polymorphisms in DNA repair genes and their association with risk of cervical cancer: A systematic review and meta‐analysis

AbstractBackgroundThere have been a large number of epidemiologic studies regarding the association between genetic polymorphisms in DNA repair genes and onset of cervical cancer. However, results are inconsistent.MethodsArticles published before June 2021 and regarding genetic polymorphisms in DNA repair genes and cervical cancer were searched in following databases: PubMed, Web of Science, Google Scholar, and CNKI. With at least three articles for each polymorphism, we made meta‐analysis to compute multivariate odds ratios (ORs) and their 95% confidence intervals (CIs).ResultsThe present study showed significant associations between XRCC1 Arg399Gln polymorphisms and risk of cervical cancer in Asian, whereas no significant association between them were showed in Caucasian (Asian: GA vs. GG: OR = 1.27, 95%CI 1.06–1.52; AA vs. GG: OR = 1.91, 95%CI 1.29–2.83; GA + AA vs. GG: OR = 1.36, 95%CI 1.12–1.65; AA vs. GG + GA: OR = 1.66, 95%CI 1.17–2.37; Caucasian: GA vs. GG: OR = 1.08, 95%CI 0.83–1.41; AA vs. GG: OR = 2.18, 95%CI 0.75–6.31; GA + AA vs. GG: OR = 1.23, 95%CI 0.85–1.78; AA vs. GG + GA: OR = 1.70, 95%CI 0.69–4.18). In addition, there were significant associations between ERCC2 rs13181 polymorphisms and risk of cervical cancer in Asian (AC vs AA: OR = 0.53, 95%CI 0.37–0.75, I2 = 0.0%, p value of Q test = 0.847; AC + CC vs AA: OR = 0.50, 95%CI 0.36–0.70, I2 = 0.0%, p value of Q test = 0.856).ConclusionsThe meta‐analysis showed that there were significant associations between XRCC1 Arg399Gln and ERCC2 rs13181 polymorphisms and risk of cervical cancer.

Round ligament suspension and vaginal purse‐string suture: Newly optimized techniques to prevent tumor spillage in laparoscopic radical trachelectomy for cervical cancer

AbstractAimThe purpose of this study was to investigate the surgical techniques and clinical feasibility of nonuterine manipulator and enclosed colpotomy to avoid cancer cell spillages in laparoscopic radical trachelectomy (LRT) for patients with early‐stage cervical cancer.MethodsWe performed the newly optimized surgical techniques of round ligament suspension and vaginal purse‐string suture in LRT in 12 patients with early‐stage cervical cancer from May 2019 to October 2020. Surgical information and postoperative results were recorded.ResultsAll 12 patients successfully underwent LRT with round ligament suspension and vaginal purse‐string suture, and no conversion to laparotomy was required. The median operation time was 268.5 min (range 200–320 min), including 5 min of round ligament suspension, and the median blood loss was 20 mL (range 5–50 mL). The median number of pelvic lymph nodes removed was 27 (range 19–35), and median amounts of paracervical tissue was 24 mm (range 21–26 mm) and vaginal tissue was 18 mm (range 16–26 mm). No intraoperative complication or serious postoperative complications were reported.ConclusionRound ligament suspension and vaginal purse‐string suture techniques are feasible and effective in LRT. They can replace uterine manipulator and unprotected colpotomy with satisfactory perioperative outcomes.

Differentially expressed EREG and SPP1 are independent prognostic markers in cervical squamous cell carcinoma

AbstractAimsCervical squamous cell carcinoma (SCC) is one of the most frequent malignancies of the female reproductive system. The malignant mechanism of SCC has not been totally clarified. We aimed to discover a list of differentially expressed genes (DEGs) to identify the malignant mechanism of cervical SCC.MethodThree expression chips (GSE7803, GSE9750, and GSE64217) were downloaded from gene expression omnibus (GEO) datasets. After standardization, 50 cervical SCC tumor tissues and 33 normal cervical tissues (NCTs) were included for DEGs and clustering analysis. RobustRankAggreg (RRA) algorithm was used to extract the overlapping DEGs. Gene function and signaling pathway analysis was implemented based on Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway databases. Protein–protein interaction (PPI) analysis and prognostic analysis were also carried out to identify the DEGs as prognostic markers for cervical SCC.ResultsTotally 100 DEGs were obtained from GSE7803, 319 DEGs from GSE9750, and 1639 DEGs from GSE64217. RRA analysis uncovered 17 upregulated DEGs and 25 downregulated DEGs. GO and KEGG analysis showed DEGs were involved in the mediation of extracellular functions, cell–cell interactions, and cell metabolism. PPI network showed a close interaction among the integrated DEGs. Prognostic analysis showed gene secreted phosphoprotein 1 (SPP1) and epiregulin (EREG) genes were independent prognostic predictors of cervical SCC.ConclusionThe gene expression profile was changed in cervical SCC tumor tissues compared to NCTs. SPP1 and EREG were postulated as prognostic markers for cervical SCC, which might be potential targets for clinical therapy of cervical SCC.

lncRNA DLG1‐AS1 promotes cervical cancer cell gemcitabine resistance by regulating miR‐16‐5p/HDGF

AbstractAimTo investigate the long non‐coding RNA DLG1 Antisense RNA 1 (lncRNA DLG1‐AS1) mechanism in cervical cancer cells with gemcitabine (GEM) resistance.MethodsQuantitative real‐time polymerase chain reaction (qRT‐PCR) was used to detect DLG1‐AS1, miR‐16‐5p, and hepatoma‐derived growth factor (HDGF) expression in cervical cancer cells. The effects of DLG1‐AS1 knockdown on cell viability, proliferation, and apoptosis were investigated in GEM‐resistant cervical cancer cells. The binding of DLG1‐AS1 with miR‐16‐5p and of miR‐16‐5p with HDGF was confirmed through dual‐luciferase reporter assays. HDGF expression was detected through Western blotting. A xenograft model was established using stably transfected GEM‐resistant cervical cancer cells to detect the role of DLG1‐AS1 in tumorigenesis in vivo.ResultsDLG1‐AS1 expression was significantly elevated in HeLa/GEM and SiHa/GEM cells. DLG1‐AS1 silencing significantly reduced the viability and proliferation of GEM‐resistant cervical cancer cells. DLG1‐AS1 also promoted GEM sensitivity in cervical cancer cells by inhibiting miR‐16‐5p. Moreover, the tumor volume in nude mice in the DLG1‐AS1 knockdown group decreased after GEM treatment. In addition, DLG1‐AS1 targeted miR‐16‐5p, and miR‐16‐5p targeted HDGF. The miR‐16‐5p inhibitor reversed the DLG1‐AS1 knockdown effect in GEM‐resistant cervical cancer cells.ConclusionKnockdown of DLG1‐AS1 promoted GEM sensitivity in cervical cancer cells by regulating miR‐16‐5p/HDGF.

Recurrent cervical cancer with PD‐L1 amplification treated with nivolumab: A case enrolled in the BELIEVE trial

AbstractPatients with cervical cancer benefiting from immune checkpoint inhibitors (ICIs) are limited. Recently, PD‐L1 amplification has been attracted attention as a reliable marker of ICIs. A 47‐year‐old woman with stage IIB cervical cancer experienced disease progression during postoperative adjuvant chemotherapy. Cancer genomic profiling revealed that the tumor was microsatellite stable with PD‐L1 amplification, therefore, nivolumab was administered by enrolling in the BELIEVE trial. Despite nivolumab treatment, remarkable disease progression was observed. At the beginning of nivolumab treatment, the patient already had multiple liver metastases with severe systemic inflammation as indicated by a high neutrophil‐to‐lymphocyte ratio (NLR), both of which are negative predictive markers for ICI. Despite the presence of PD‐L1 amplification, nivolumab was ineffective in cancer progression, which may be attributable to the presence of liver metastasis and high NLR. ICI is recommended to be administered at an early stage of cancer treatment to enhance its effectiveness.

Fertility‐sparing surgery for early‐stage cervical cancer: A case series study on the efficacy and feasibility of cervical conization followed by pelvic lymphadenectomy

AbstractObjectivesTo evaluate the oncologic and obstetric outcomes of cervical conization followed by pelvic lymphadenectomy, which is used as a fertility‐sparing procedure, in reproductive‐aged patients with early‐stage cervical cancer.MethodsWe performed a retrospective study of patients with stage IA1–IB1 cervical cancer who underwent cervical conization followed by pelvic lymphadenectomy from 2011 to 2020 at Kumamoto University Hospital.ResultsIn total, eight patients underwent conization followed by pelvic lymphadenectomy. The median age of the patients was 33 (range: 28–36) years. Four (50.0%) patients were nulliparous. Seven (87.5%) patients were diagnosed with squamous cell carcinoma (87.5%) and one (12.5%) with adenocarcinoma. Five (62.5%), two (25.0%), and one (12.5%) presented with stage IA1, IA2, and IB1 disease, respectively. Five (62.5%) patients had lymphovascular space invasion (LVSI) based on the assessment of specimens obtained via conization. However, none had lymph node metastasis based on pelvic lymphadenectomy. Regarding long‐term oncologic outcomes, recurrence was not observed at a median follow‐up of 60 (range: 8–107) months. In addition, obstetric outcomes were consistently favorable in terms of achieving pregnancy, preterm delivery, and live birth. During the study period, two patients who actively attempted to conceive had four pregnancies, resulting in full‐term deliveries, and one was on her first trimester of pregnancy.ConclusionCervical conization combined with pelvic lymphadenectomy represents a feasible conservative management for histologically well‐selected patients with early‐stage cervical cancer. Furthermore, an optimal histopathological evaluation of conization specimens will contribute to decision‐making regarding the use of this fertility‐sparing procedure.

Challenge to improve Japan's deplorable HPV vaccination rate by local government actions

AbstractAimIn Japan, in 2013, following reports of several alleged adverse reactions in young girls following vaccination, the previously successful national human papillomavirus infection (HPV) vaccination program collapsed rapidly. In the 8 years since vaccination rates have hovered near zero. In October of 2020, in an attempt to mitigate this lingering disaster, the Japanese Ministry of Health, Labor, and Welfare (MHLW) agency finally revised its HPV vaccination informational leaflet that was designed to be distributed by local governments nationwide. Prior to this revision, Toyonaka City, in Japan's Osaka province, had already begun sending out their own unique leaflet to girls in the targeted 6th–10th grades. As a preview of how MHLW's revised leaflet might eventually succeed, we have studied the HPV vaccination results from Toyonaka City's experiment.MethodThis study was a population‐based analysis that compared the monthly rates of new vaccinations in girls of a targeted grade school age group. We looked at rates before and after the leaflets were sent by Toyonaka City's Division of Health Promotion and Senior Services.ResultsThe vaccination rates between April 2020 and March 2021 were improved across all grades; 1.2% in 6th grade (p = 0.000185), 2.5% in 7th grade (p < 0.0001), 3.5% in 8th grade (p < 0.0001), 6.8% in 9th grade (p < 0.0001), and a remarkable 16.5% in 10th grade (p < 0.0001).ConclusionWhen a local government sends an HPV informational leaflet targeted at young girls, it can significantly improve their HPV vaccination rates.

LncRNA Opa interacting protein 5‐antisense RNA 1 (OIP5‐AS1) promotes the migration, invasion and epithelial‐mesenchymal transition (EMT) through targeting miR‐147a/insulin‐like growth factor 1 receptor (IGF1R) pathway in cervical cancer tissues and cell model

AbstractBackgroundTwo factors involved in regulation, long noncoding RNA Opa interacting protein 5‐antisense RNA 1 (lncRNA OIP5‐AS1) and microRNA‐147a, were found in cervical cancer. Therefore, the investigation of the specific regulation of miR‐147a by OIP5‐AS1 was performed in cervical cancer.MethodThe cervical cancer tissues were collected from patients with cervical cancer (n = 50). The expression of OIP5‐AS1, miR‐147a, proteins in epithelial‐mesenchymal transition (EMT) process and insulin‐like growth factor 1 receptor (IGF1R) were measured by quantitative real‐time polymerase chain reaction (qRT‐PCT) or western blotting. Cell motility and the relationship between OIP5‐AS1 and miR‐147a were detected or analyzed by wound healing test, Transwell assay, dual‐luciferase reporter assay, RNA binding protein immunoprecipitation assay or Pearson correlation in OIP5‐AS1, or miR‐147a over‐expressed and/or suppressed cervical cancer cells.ResultsOIP5‐AS1 showed the high‐expression and miR‐147a showed the low‐expression in tumor tissues collected from patients with cervical cancer and cell lines Hela, CaSki, Siha, and ME‐180. The low‐expression of OIP5‐AS1 suppressed the motility of Caski cells, as well as up‐regulated the level of E‐cadherin, which a key protein in EMT. There were targeting sites between miR‐147a and OIP5‐AS1. OIP5‐AS1 induced the down‐regulation of miR‐147a, so miR‐147a was inversely correlated with OIP5‐AS1. The down‐regulation of miR‐147a increased IGF1R and E‐cadherin, and these increases were alleviated by OIP5‐AS1 knockdown.ConclusionLncRNA OIP5‐AS1 promotes the migration, invasion and EMT of cervical cancer cells via targeting miR‐147a/IGF1R pathway.

A simplified procedure of nerve‐sparing radical hysterectomy

AbstractAimWe devised a simplified nerve‐sparing radical hysterectomy that is simpler than commonly used procedures.MethodsWe retrospectively examined 16 cases of classical non‐nerve‐sparing radical hysterectomy (non‐nerve‐sparing group) and 16 cases of simplified nerve‐sparing radical hysterectomy (nerve‐sparing group) performed between 2019 and 2020. We examined and compared the duration of surgery, blood loss, perioperative complications, postoperative urinary function (presence or absence of urinary sensation, number of days with residual urine measurement, and frequency and duration of oral sustained release urapidil capsules and self‐catheterization), and short‐term prognosis between the two groups.ResultsCompared to conventional non‐nerve‐sparing radical hysterectomy, the duration of surgery for nerve‐sparing radical hysterectomy was significantly shorter (407 [339–555] min vs. 212 [180–356] min; p < 0.001), and blood loss was significantly less. Compared to the nerve‐sparing group, the non‐nerve‐sparing group had more cases of oral urapidil use and a higher frequency of clean intermittent catheterization. Clean intermittent catheterization was required in two cases in the nerve‐sparing group; however, it was withdrawn at 180 and 240 days. Conversely, clean intermittent catheterization was still required in three cases in the non‐nerve‐sparing group. There were no statistically significant differences in progression‐free survival and overall survival between the two groups.ConclusionThe simple nerve‐sparing radical hysterectomy resulted in shorter duration of surgery and less blood loss as well as in a clear improvement in the postoperative urinary status and short‐term prognosis. This technique simplifies nerve‐sparing radical hysterectomy, which is commonly thought to be complicated, making it easier to understand.

Synchronous Presentation of Gastric‐Type Adenocarcinoma In Situ of Cervix and Vagina in a Young Adult Female: A Precursor Seldom Seen

ABSTRACT Synchronous human papillomavirus‐independent gastric‐type adenocarcinoma in situ affecting both cervical and vaginal epithelium constitutes an ultrarare preinvasive disease. The diagnostic complexity arises from asymptomatic presentation and skip lesions that obscure the true extent of the disease. We report the case of a 26‐year‐old woman diagnosed with atypical glandular cells during routine cervical cancer screening. Sequential conizations consistently demonstrated gastric‐type adenocarcinoma in situ with persistently positive surgical margins. Post‐conization colposcopic assessment and histopathology revealed extensive multifocal disease involving residual cervix and vaginum. Considering the substantial disease burden and potential for occult invasion, surgical intervention was undertaken, including type B1 radical hysterectomy, bilateral salpingectomy, bilateral ovarian tissue cryopreservation, total vaginectomy, and vaginal reconstruction. At 20 months of follow‐up, the patient remains completely disease‐free with no evidence of recurrence.

Efficacy of Postoperative Para‐Aortic and Pelvic Lymphadenectomies for Intermediate‐ to High‐Risk Endometrial Cancer

ABSTRACT Purpose A two‐stage surgery for endometrial cancer is associated with a high physical and psychological burden on the patient and possibly increases the risk of subsequent abdominal surgeries. In this study, we aimed to characterize the oncological features of endometrial cancer patients with lymph node‐positive and lymph node‐recurrent disease who underwent two‐stage lymphadenectomy after initial hysterectomy without pelvic and para‐aortic lymphadenectomy and were at intermediate or high risk for postoperative recurrence. Methods This single‐center retrospective study evaluated a total of 37 patients with endometrial cancer who underwent postoperative para‐aortic lymphadenectomy between April 2020 and March 2023. Results The median follow‐up duration was 42 months. The 3‐year survival rate was 90%, and the 3‐year recurrence‐free survival rate was 80%. Lymph node metastasis occurred in 13.5% of the patients, of whom 2.7% had skip metastases in the para‐aortic lymph nodes only. Histologically, most patients (80%) had endometrioid carcinoma grade 1. Overall recurrence was observed in 16.2%. The median recurrence‐free survival time was 20.5 months. Poorly differentiated or non‐endometrioid histology was found in 66.6% of the patients. All patients with low‐grade endometrioid carcinoma with lymph node metastasis or recurrence had p53 mutations. Conclusion No patients with lymph node metastasis relapsed during the follow‐up period. Two‐stage lymphadenectomy may have contributed to the favorable outcomes. However, it is difficult to perform molecular pathological evaluation in all cases preoperatively. Therefore, it is acceptable to perform a hysterectomy and undergo a two‐stage lymphadenectomy in minimally invasive surgery according to risk classification.

Associations of Lipid Metabolism Abnormalities and Obesity With Endometriosis‐Associated Ovarian Cancer

ABSTRACT Aim To investigate the differences in lipid metabolism and obesity between patients with ovarian endometrioid carcinoma (OEC) and ovarian clear cell carcinoma (OCCC), both of which are classified as endometriosis‐associated Type I ovarian cancers. Methods This retrospective study included 133 patients who underwent surgery for OEC ( n  = 50) or OCCC ( n  = 83) between 2010 and 2022. Preoperative serum lipid markers (total cholesterol [TC], low‐density lipoprotein cholesterol [LDL‐C], and high‐density lipoprotein cholesterol [HDL‐C]) and body mass index (BMI) were compared between the two groups. Associations with menopausal status and disease stage were examined, and independent predictors were evaluated by multivariate logistic regression. Results Patients with OEC had significantly higher TC (215 vs. 199.5 mg/dL, p  = 0.040), LDL‐C (139 vs. 120.6 mg/dL, p  = 0.026), and BMI (22.1 vs. 20.4 kg/m 2 , p  = 0.020) compared with those with OCCC. No significant differences were observed for HDL‐C. In premenopausal women, TC and LDL‐C were significantly higher in patients with OEC, whereas no intergroup differences were found in postmenopausal women. Among patients with OEC, those with advanced‐stage disease had higher TC and LDL‐C, whereas no stage‐related differences were observed in patients with OCCC. Multivariate analysis identified BMI and LDL‐C as independent factors associated with OEC. Conclusion Lipid metabolism abnormalities and obesity were more strongly associated with OEC than with OCCC, suggesting subtype‐specific metabolic mechanisms of carcinogenesis and progression. These findings highlight the importance of metabolic factors in OEC, warranting further prospective studies.

Current Status of Fertility‐Sparing Treatment for Gynecological Cancers in Japan: A Nationwide Survey

ABSTRACT Aim There is an increasing demand for fertility‐sparing treatment (FST) among young women with gynecological cancer. This study aimed to clarify the current status of FST implementation across Japan by focusing on institutional practice patterns and clinical protocols for cervical, endometrial, and ovarian cancers. Methods A nationwide cross‐sectional survey was conducted between August and September 2024. An online questionnaire was distributed to 481 gynecologic tumor registry institutions through the Japan Society of Obstetrics and Gynecology mailing list. Data on institutional characteristics, specific FST eligibility criteria, treatment methods, and post‐treatment management were collected. Results Responses were received from 226 institutions (response rate: 47.0%), and all respondent institutions (100%) performed FST for at least one gynecological cancer. Although FST is widely available, significant heterogeneity in clinical protocols was observed across all three cancers. Key variations among respondent institutions included a low implementation rate of radical trachelectomy for cervical cancer (20.8%), a high rate of post‐FST hysterectomy for endometrial cancer (63.6%) compared to cervical cancer and ovarian cancer, and exclusion criteria for patients with hereditary cancer syndromes. Conclusion FST is an established practice in Japan; however, there is a lack of consensus regarding its clinical application. These findings provide a critical benchmark for future efforts to standardize care and develop collaborative networks to optimize this essential treatment modality for young patients with gynecological cancer.

Resolution of pelvic postoperative spindle cell nodule with sarcomatous onset after 9 years of follow‐up

AbstractIntroductionPostoperative spindle cell nodules are benign and reactive lesions that occur at the previous surgical site. It often develops like a sarcoma and is resected via highly invasive procedures. To date, there have been no published reports on the natural progression of postoperative spindle cell nodules without surgical intervention.CaseA 45‐year‐old woman underwent a total abdominal hysterectomy for leiomyoma. A 5‐cm pelvic mass exposed in the vaginal stump developed 7 weeks later, causing genital bleeding. Positron emission tomography–computed tomography revealed a pelvic mass and an enlarged pelvic lymph node with high uptake. We suspected an invasive sarcoma in the pelvis. However, through a transvaginal needle biopsy, the mass was diagnosed as a postoperative spindle cell nodule posthysterectomy. The nodule slowly reduced in size and completely disappeared 9 years posthysterectomy.ConclusionsCorrect diagnosis of this nodule with sarcomatous onset based on biopsy was important to avoid unnecessary surgeries. The lesion completely disappeared spontaneously after long‐term follow‐up.

Correlation of PD‐L1 Expression With Microsatellite Instability and p53 Status in Endometrial Cancer: A Clinicopathological and Molecular Analysis

ABSTRACT Aim This study aimed to evaluate the correlations between programmed death‐ligand 1 ( PD‐L1 ) expression, the mismatch repair system, and p53 status in endometrial cancer, considering tumor stage. Methods A retrospective analysis of clinicopathological and immunohistochemical data was conducted on 254 patients treated at Holy Cross Cancer Centre (Poland). The majority of patients had endometrioid adenocarcinoma (89.8%) and FIGO stage I disease (69.7%). Results Positive PD‐L1 expression (threshold ≥ 1%) was observed in only 3.9% of cases, while mismatch repair system deficiency and aberrant p53 expression were present in 18.1% and 17.3%, respectively. No significant correlations were found between PD‐L1 expression and clinicopathological parameters, repair system status, or p53 ( p  = 0.328 and p  = 0.359, respectively). However, a significant association ( p  = 0.046) was noted between PD‐L1 positivity and the microsatellite‐unstable/hypermutated molecular subtype, with 30% of PD‐L1 positive tumors exhibiting this subtype compared to 10.2% of PD‐L1 negative tumors. Conclusions No molecular marker demonstrated a significant association with recurrence risk ( p  > 0.05), in contrast to the FIGO stage, which showed a significant correlation ( p  < 0.001). Although PD‐L1 expression was rare, it was significantly associated with microsatellite instability, highlighting the potential of molecular classification to identify candidates for immunotherapy. However, the low frequency of PD‐L1 positivity and the small sample size warrant caution in interpreting these findings, and further research is needed to confirm the clinical relevance of PD‐L1 in endometrial cancer.

Novel Approaches for Detecting TP53 Mutations and Targeted Therapeutic Strategies: Emerging Insights Into Cytoplasmic p53 Aggregates in Ovarian Cancer

ABSTRACT Background Ovarian cancers have been the most lethal gynecologic malignancies worldwide, with survival outcomes remaining poor despite therapeutic advances. Since TP53 is the most frequently mutated gene in ovarian cancers, it highlights the central role of p53 dysfunction in promoting tumor initiation, genomic instability, and progression. Beyond classical loss of transcriptional activity, mutant p53 may exert dominant‐negative effects on residual wild‐type protein and acquire oncogenic gain‐of‐function properties that promote invasion, metastasis, and resistance to chemotherapy. Nevertheless, despite extensive efforts, effective therapeutic agents targeting TP53 ‐mutant tumors remain elusive, representing a major unmet medical need. Methods The published articles were reviewed. Results To detect the TP53 mutations, driven by recent technological innovations, circulating tumor DNA has emerged as a powerful and minimally invasive biomarker that enables the detection of gene mutations and the real‐time monitoring of tumor evolution, minimal residual disease, and therapeutic resistance. Bridging diagnostics and therapy, recent discoveries highlight that cytoplasmic p53 aggregates as a clinically adverse phenotype in high‐grade serous ovarian cancers, elucidating mechanisms of aggregate formation and propagation. By restoring p53 conformation and transcriptional activity through distinct molecular mechanisms, pharmacologic reactivation of mutant p53 holds promise as a novel therapeutic strategy. Conclusion These advances indicate that TP53 disruption, once deemed untargetable, may become a new cornerstone of precision oncology in ovarian cancer.

Association Between Adipose Tissue Distribution and Survival in Recurrent Ovarian Cancer Patients Treated With Anti‐ VEGF Therapy: A Retrospective CT ‐Based Analysis

ABSTRACT Objective The aim of this study was to evaluate the effect of visceral, subcutaneous and intermuscular adipose tissue areas measured by computed tomography at diagnosis on survival in ovarian cancer patients receiving second‐line bevacizumab treatment. Materials and Methods This retrospective study included 41 ovarian cancer patients who received second‐line bevacizumab treatment at Istanbul University Oncology Institute between 2009 and 2024. Visceral, subcutaneous and intermuscular adipose tissue areas at the L3 and T12 vertebral levels were measured from the computed tomography images of the patients at the time of diagnosis, and these areas were normalized by the square of body height and index values (cm 2 /m 2 ) were calculated. The effect of adipose tissue parameters on overall survival and disease‐free survival was analyzed. Results In multivariate analysis, only subcutaneous adipose tissue at the T12 level was found to be an independent predictor of overall survival. Subgroup analyses also showed that survival was significantly shorter in patients with low subcutaneous fat area or index. Similarly, low body mass index was also associated with unfavorable survival outcomes. Visceral and intermuscular adipose tissue parameters had no significant effect on survival. Conclusion Subcutaneous adipose tissue measured by diagnostic computed tomography may serve as a potential prognostic biomarker in ovarian cancer patients. These findings support the integration of body composition analysis into clinical decision‐making processes.

Retrospective comparative study of robot‐assisted surgery, laparoscopic surgery, and laparotomy for endometrial cancer in patients with a low risk of recurrence

AbstractAimMinimally invasive surgeries for endometrial cancer are increasing worldwide. In Japan, some articles have examined surgical outcomes, but only a few have addressed oncological outcomes. This study aims to compare robot surgery, laparoscopic surgery, and laparotomy in terms of surgical and oncological outcomes within a low‐risk group for endometrial cancer recurrence.MethodsThis study included patients with endometrial cancer deemed to be at low risk of recurrence and who underwent surgery between January 2011 and December 2020. We studied 99 patients who underwent robot surgery, 85 patients who underwent laparotomy, and 77 patients who underwent laparoscopic surgery. Surgical and oncological outcomes were compared retrospectively for these groups of patients.ResultsThe median follow‐up period was 47, 61, and 60 months in the laparotomy, laparoscopy, and robotic groups, respectively. The three groups had similar perioperative and pathological data. No significant differences in overall survival and disease‐free survival were observed among the groups. Univariate and multivariate analyses conducted on the overall study population for disease‐free survival and overall survival showed that the surgical approach did not have any influence. Minimally invasive surgery groups had longer operating times compared to the laparotomy group, but they had significantly less blood loss. The number of resected pelvic lymph nodes was similar, and the complication rate was not significant.ConclusionsRobot‐assisted surgery and laparoscopic surgery were found to be less invasive and showed similar oncologic outcomes compared to laparotomy surgery for endometrial cancer in patients with a low risk of recurrence.

Smoking and Ovarian Cancer Awareness: Assessing the Impact on Knowledge and Perception Among Adult Women

ABSTRACT Background The effects of smoking status, which is a risk factor for many cancers, on ovarian cancer awareness in women has not yet been adequately investigated. Aims The aim of this study was to determine the relationship between smoking status and ovarian cancer awareness levels in women. Methods This descriptive study was conducted with the help of an online questionnaire form between 22.03.2023 and 22.05.2023 among volunteer women over the age of 18. No sample calculation was made. The questionnaire included 15 questions about sociodemographic and health‐related data and the Ovarian Cancer Awareness Scale (Cronbach's alpha = 0.768). Results 228 women participated in the study. The mean age of the participants was 36.71 ± 11.59 years, 85.5% were university graduates, 21.9% were health personnel and 26.8% were smokers. It was determined that 44.3% of the participants had a family history of cancer and 32.7% of them had gynecologic cancer. In our study, the mean score of the ovarian cancer awareness scale was 47.75 ± 14.62. The level of ovarian cancer awareness was found to be statistically significantly higher in university graduates, health personnel and non‐smokers ( p  < 0.001, p  < 0.001, p  = 0.003, respectively). A weak negative correlation was observed with age and smoking duration and ovarian cancer awareness scores ( p  = 0.001, r  = −0.212; p  = 0.037, r  = −0.274, respectively). Conclusion In conclusion, the findings suggest that smoking may have a negative impact on ovarian cancer awareness and suggest that efforts to increase women's awareness of ovarian cancer through smoking cessation campaigns and health education programs may be more effective, with a particular focus on smokers.

Annual Report of the Committee on Gynecologic Oncology, the Japan Society of Obstetrics and Gynecology: Annual Patient Report for 2022 and Annual Treatment Report for 2017

ABSTRACT Aim To provide information including the trend of gynecological malignancies in Japan, we hereby present the Annual Patient Report for 2022 and the Annual Treatment Report for 2017, on the outcomes of patients who started treatment in 2017. Methods The Japan Society of Obstetrics and Gynecology maintains an annual tumor registry, where information on gynecological malignancies from various participating institutions is gathered. The data of patients whose treatment with gynecologic malignancies was initiated in 2022 were analyzed retrospectively. Survival of the patients who started treatment with cervical, endometrial, and ovarian cancer in 2017 was analyzed by using the Kaplan–Meier, log–rank, and Wilcoxson tests. Results Treatment was initiated in 2022 for 8039 patients with cervical cancer, 14 518 with endometrial cancer, 8524 with ovarian, tubal, and peritoneal cancer, 2360 with ovarian borderline tumors, and with the others (270 vulvar cancer, 179 vaginal cancer, 539 uterine sarcoma, 48 uterine adenosarcoma, 158 trophoblastic diseases). This clinicopathological information was summarized as the Patient Annual Report. The 5‐year survival rates of the patients who initiated treatment in 2017 were as follows. For cervical cancer, the rates were 93.0%, 76.1%, 59.5%, and 28.3% for Stages I, II, III, and IV, respectively. For endometrial cancer, the rates were 94.9%, 88.8%, 72.7%, and 28.9% for Stages I, II, III, and IV, respectively. For ovarian cancer, the rates were 91.7%, 76.6%, 54.4%, and 45.2% for Stages I, II, III, and IV, respectively. Conclusion The annual tumor report is an important survey that provides knowledge on gynecological malignancy trends in Japan.

The Expression and Clinical Significance of C1orf106 in Low‐Grade Serous Ovarian Cancer

ABSTRACT Aim Low‐grade serous ovarian cancer (LGSOC) is a rare subtype of ovarian cancer with distinct biological behavior. This study aimed to identify new biomarkers with potential diagnostic and prognostic value for LGSOC. Methods Gene‐expression data were downloaded from the Gene Expression Omnibus (GEO). Differentially expressed genes (DEGs) were identified using R. Functional enrichment analyses were conducted to determine the biological functions and signaling pathways associated with DEGs. The mitogen‐activated protein kinase (MAPK) pathway‐related gene, chromosome 1 open reading frame 106 ( C1orf106 ), was selected as the target gene. Immunohistochemistry and quantitative real‐time polymerase chain reaction (qRT‐PCR) were performed to verify its expression. Associations between C1orf106 expression and the clinical features of patients were analyzed using the chi‐square ( χ 2 ) test. Prognostic significance was evaluated with survival analyses. Results A total of 3099 upregulated and 4968 downregulated genes were identified in LGSOC. Gene set enrichment analysis (GSEA) demonstrated significant alterations in KRAS signaling and metabolic pathways between LGSOC and healthy controls. Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO) analyses revealed enrichment in immune response and MAPK pathway alterations. Immunohistochemistry and qRT‐PCR confirmed that C1orf106 expression in LGSOC tissues was significantly higher than in normal ovarian tissues. Clinically, high C1orf106 expression was associated with lower BMI (< 25 kg/m 2 ), the absence of visible residual disease, and improved progression‐free survival (PFS) and overall survival (OS) in univariate Cox and Kaplan–Meier analyses. Conclusions C1orf106 may serve as a promising marker for the diagnosis and prognosis of LGSOC.

Preoperative Diagnosis of Small Bowel Metastasis of Ovarian Clear Cell Carcinoma Using Capsule and Double‐Balloon Endoscopy: A Case Report

ABSTRACT We present a rare case of small bowel metastasis of ovarian clear cell carcinoma, successfully diagnosed preoperatively using capsule and double‐balloon endoscopy. The patient was a 62‐year‐old woman who underwent primary surgery for stage IIB ovarian clear cell carcinoma followed by six cycles of adjuvant chemotherapy. Six years later, she developed iron‐deficiency anemia with melena, but conventional upper and lower endoscopy failed to identify the source of bleeding. Subsequent capsule endoscopy revealed a tumor in the distal ileum, and a biopsy was taken using double‐balloon endoscopy. Pathological and immunohistochemical findings supported a diagnosis of recurrent ovarian clear cell carcinoma. Surgical resection was performed, followed by chemotherapy, and the patient remains recurrence‐free. This is the first case of small bowel metastasis of ovarian clear cell carcinoma diagnosed preoperatively with endoscopic biopsy. It highlights the criticality of advanced endoscopic modalities for evaluating unexplained anemia in patients with a history of ovarian cancer.

Premature mortality due to cervical and ovarian cancers in Japan, 2000 to 2020

AbstractAimUsing the national Japanese mortality data, we investigated whether there has been an improvement in the lifespan among Japanese women who died from cervical and ovarian cancers from the years 2000 through 2020.MethodsThe number of deaths due to cervical and ovarian cancers in Japan was obtained from the World Health Organization mortality database. We calculated age standardized rates (ASR) using the direct method adjusted to the World Standard Population. Years of life lost (YLL) due to those cancers were calculated using Japanese life tables. Average lifespan shortened (ALSS) measure was calculated as a ratio of YLL to the expected lifespan. We used the bootstrap method to calculate the 95% confidence interval (95% CI) for the ALSS measure.ResultsThe ASR for death remained mostly stable over the study at about two deaths per 100 000 women for cervical cancer, and three deaths for ovarian cancer. The ALSS values report that women who died from cervical cancer lost on average 28.3% of their lifespan (95% CI: 27.7–28.9) in 2000 and 26.6% (26.1–27.2) in 2020. Women who died from ovarian cancer lost on average 26.9% (26.5–27.4) and 23.5% (23.1–23.9) of their lifespan in 2000 and 2020, respectively.ConclusionThe ALSS results show that over a 20‐year period, women who died of cervical and ovary cancers in Japan had their lifespans prolonged by about two and three percentage points, respectively.

Annual report of the committee on gynecologic oncology, the Japan Society of Obstetrics and Gynecology: Annual patient report for 2021 and annual treatment report for 2016

AbstractAimTo provide information including the trend of gynecological malignancies in Japan, we hereby present the Annual Patient Report for 2021 and the Annual Treatment Report for 2016, on the outcomes of patients who started treatment in 2016.MethodsThe Japan Society of Obstetrics and Gynecology maintains an annual tumor registry, where information on gynecological malignancies from various participating institutions is gathered. The data of patients whose treatment with gynecologic malignancies was initiated in 2021 were analyzed retrospectively. Survival of the patients who started treatment with cervical, endometrial, and ovarian cancer in 2016 was analyzed by using the Kaplan–Meier, log‐rank, and Wilcoxson tests.ResultsTreatment was initiated in 2021 for 8006 patients with cervical cancer, 13 912 with endometrial cancer, 8337 with ovarian, tubal, and peritoneal cancer, 2375 with ovarian borderline tumors, and with the others (226 vulvar cancer, 161 vaginal cancer, 437 uterine sarcoma, 47 uterine adenosarcoma, 160 trophoblastic diseases). This clinicopathological information was summarized as the Patient Annual Report. The 5‐year survival rates of the patients with cervical cancer were 92.3%, 77.0%, 56.1%, and 30.3% for stages I, II, III, and IV, respectively. The 5‐year survival rates for the patients with endometrial cancer were 94.1%, 88.8%, 71.2%, and 24.5% for stages I, II, III, and IV, respectively. The 5‐year survival rates for the patients with ovarian cancer (surface epithelial‐stromal tumors) were 91.3%, 78.8%, 54.3%, and 36.8% for stages I, II, III, and IV, respectively.ConclusionThe annual tumor report is an important survey that provides knowledge on gynecological malignancy trends in Japan.

A case of BRAF mutation‐positive recurrent ovarian high‐grade serous carcinoma with remarkable response to combined dabrafenib and trametinib therapy

Abstract Comprehensive genomic profiling (CGP) testing is increasingly used to identify new treatment options for solid tumors lacking standard therapies. While dabrafenib and trametinib combination therapy has shown efficacy in BRAF mutation‐positive solid tumors, reports in gynecologic cancers are limited. We report a case of a patient with BRAF mutation‐positive recurrent ovarian high‐grade serous carcinoma who showed a remarkable response to dabrafenib and trametinib. The patient initially received monotherapy but experienced disease progression. CGP testing revealed a BRAF mutation, leading to the initiation of combination therapy. Tumor markers significantly decreased, and the recurrent pelvic lesion shrank markedly, resulting in a complete response. The patient remains recurrence‐free after 9 months of treatment. This case underscores the importance of CGP testing in identifying targeted therapies for solid tumors without standard treatment options.

A live birth after bilateral salpingo‐oophorectomy for seromucinous borderline ovarian tumor

AbstractBorderline ovarian tumors primarily affect younger women and are associated with favorable prognosis, making fertility‐sparing surgery a viable option. However, owing to recurrence and malignant transformation risks, careful monitoring is required. Seromucinous borderline ovarian tumors, a rare subtype that is often associated with endometriosis, lack standardized guidelines for fertility‐sparing surgery or infertility management following bilateral salpingo‐oophorectomy with uterine preservation. We present a case of bilateral seromucinous borderline ovarian tumors stage IC3 managed with bilateral salpingo‐oophorectomy, without observed recurrence, resulting in a live birth after frozen–thawed embryo transfer using embryos preserved before surgery. This case highlights the feasibility of bilateral salpingo‐oophorectomy with uterine preservation and hormone replacement therapy‐assisted frozen–thawed embryo transfer for seromucinous borderline ovarian tumors, emphasizing the importance of long‐term surveillance and multidisciplinary management. Further research is required to establish evidence‐based guidelines for seromucinous borderline ovarian tumor treatment and infertility care post‐bilateral salpingo‐oophorectomy.

Primary chondrosarcoma of the ovary

AbstractOvarian heterologous sarcoma is a rare malignancy. Only three cases of ovarian chondrosarcoma have been reported in the literature, and almost all of these were components of ovarian teratomas. Herein, we report the clinicopathological characteristics of an ovarian chondrosarcoma in a 68‐year‐old woman who had previously undergone total hysterectomy. She had no subjective symptoms, and the tumor was unexpectedly found by further examination of osteoarthritis of the hip joint. Preoperative magnetic resonance imaging revealed curious findings of a lobulated high‐intensity component with a leaf‐vein‐like low‐intensity component. Computed tomography revealed irregularly distributed ossification extending to the entire tumor. Preoperative levels of CA125, CA19‐9, carcinoembryonic antigen, α‐fetoprotein, and lactic dehydrogenase were all within normal limits. Macroscopic findings of the surgically resected tumor and pathologic findings revealed no teratoma component in the tumor. Finally, we diagnosed the tumor as a primary chondrosarcoma of the ovary.

Updates and advances for gynecologic imaging

Abstract A gynecologic malignancy is one of the most common cancers affecting females and is responsible for significant rates of morbidity and mortality throughout the world. Early discovery and accurate staging, as well as early recurrence detection and correct assessment of therapeutic response, are important factors for patient management and survival. For detection and characterization, as well as staging and restaging of gynecologic conditions most commonly encountered, that is, cervical, endometrial, and ovarian malignancy, the usage of ultrasound, analysis of images obtained with computed tomography (CT), magnetic resonance imaging, and positron emission tomography–CT has critical roles. Recently, artificial intelligence used to extract quantitative information from radiological imaging has become an important factor for treatment decisions. The present review article provides important information related to recent advances in gynecologic malignancy imaging options, with a focus on findings related to cervical, endometrial, and ovarian neoplasms.

Synchronous endometrial and ovarian cancers originating from distinct clonal lineages in Lynch syndrome: A case report and review of the literature

Abstract Recent next‐generation sequencing (NGS) studies have shown that synchronous endometrial and ovarian cancers (SEOCs) are often derived from the same clone. However, the clonal relationship in Lynch syndrome remains unclear. A 45‐year‐old woman was diagnosed with grade 2 endometrial endometrioid carcinoma and an ovarian yolk sac tumor with clear cell carcinoma. Genetic testing revealed different MLH1 variants in the endometrial and ovarian cancers, and peripheral blood analysis identified an exon 5 deletion in MLH1 , confirming Lynch syndrome. The somatic variants in the tumors were distinct. A review of the literature found six cases of SEOC in Lynch syndrome with NGS‐based clonal analysis, four of which (67%) showed independent cancers with different somatic profiles. These findings suggest that, unlike sporadic SEOC, synchronous cancers in Lynch syndrome are more likely to arise from separate clones.

The involvement of ribonucleoproteins in promoting epithelial ovarian cancer through a systems biology approach

Abstract Background Epithelial ovarian cancer (EOC), originating from the ovarian epithelial cells, represents approximately 90% of all ovarian cancer cases and includes several subtypes. Aim This study investigates the role of hub ribonucleoprotein genes in EOC progression. Methods Microarray datasets GSE28799 and GSE54388 from GEO were analyzed using Transcriptome Analysis Console (TAC) software for differential expression ( p  ≤ 0.05, LogFC ≥4). Upregulated RNP genes, including FBL and HNRNPC, were identified. Protein–protein interactions were analyzed using STRING and visualized in Cytoscape. Clustering was performed with Gephi software. Gene expression and alterations were validated using the HPA and cBioPortal databases. Results FBL and HNRNPC were significantly upregulated in EOC, playing key roles in tumor progression. Network analysis showed close interactions within the same gene cluster. Pathway enrichment linked them to spliceosome and ribosome biogenesis, affecting gene regulation and cellular function. Samples with FBL and HNRNPC deletions showed lower mRNA expression. Survival analysis indicated that their upregulation negatively affects patient survival, suggesting that disrupting these genes could slow cancer progression. Conclusion This study highlights the crucial role of FBL and HNRNPC in EOC. These genes are significantly upregulated and actively contribute to key cellular processes like spliceosome function and ribosome biogenesis, which help sustain tumor growth. Through network and pathway analyses, researchers have uncovered their strong functional connection, further emphasizing their importance in cancer biology. Notably, higher expression levels of these genes are linked to poorer patient survival. Targeting and disrupting their expression may provide new strategies to slow tumor progression and improve patient outcomes.

Diagnostic challenges in uterine tumor resembling ovarian sex cord tumor: Two case reports

Abstract Uterine tumors resembling ovarian sex cord tumors (UTROSCTs) are rare neoplasms, with cervical involvement posing exceptional diagnostic challenges. We report two cases: Case 1: a 43‐year‐old woman presenting with abnormal uterine bleeding and a cervical mass. An initial biopsy misinterpreted the lesion as a perivascular epithelioid cell tumor (PEComa), resulting in modified radical hysterectomy, bilateral salpingo‐oophorectomy, and pelvic lymphadenectomy. Subsequent multi‐institutional histopathological consultation confirmed cervical UTROSCT. Case 2: a 53‐year‐old postmenopausal woman underwent hysteroscopic resection for endometrial thickening revealing UTROSCT, prompting total hysterectomy with bilateral salpingo‐oophorectomy. Both patients remain disease‐free at 72 and 3 months postoperatively. These cases highlight UTROSCT's non‐specific imaging features and frequent histomorphologic overlap with other benign and malignant entities, particularly in the cervix, necessitating immunohistochemical differentiation. Case 1 underscores how diagnostic error can lead to overtreatment. Comprehensive immunohistochemical evaluation is critical for accurate diagnosis. Although total hysterectomy remains standard management, fertility‐sparing options may be appropriate for select patients. Long‐term surveillance is recommended due to the risk of recurrence.

Pathogenesis and MRI findings in two cases of seromucinous borderline tumors coexisting with carcinoma in endometriotic cysts: Case reports and literature review

Abstract Seromucinous borderline tumors (SMBTs) generally have a favorable prognosis, and fertility‐preserving surgery may be indicated. However, SMBT may occasionally coexist with carcinoma, necessitating careful management. This report presents two cases of SMBT coexisting with carcinoma within endometriotic cysts and reviews pathogenesis mechanisms with MRI‐pathological correlations. In both cases, SMBT components appeared as papillary or nodular projections with prominent high signal intensity on T2WI, no diffusion restriction on DWI, and gradual, weak enhancement on dynamic contrast‐enhanced (DCE) MRI. In contrast, coexisting carcinoma components showed intermediate signal intensity on T2WI, diffusion restriction on DWI, and rapid, intense enhancement on DCE‐MRI. As it affects prognosis and treatment strategy, assessing the coexistence of carcinoma with SMBT is essential. This is the first report to demonstrate the usefulness of multiparametric MRI, including DWI and DCE‐MRI, in evaluating SMBT and coexisting carcinoma in endometriotic cysts.

The peripheral cysts sign of ovarian thecoma‐fibroma groups: Incidence and diagnostic value

Abstract Aims To investigate the incidence of the peripheral cysts sign of ovarian thecoma‐fibroma groups (OTFGs), and to discuss the value of the peripheral cysts sign in the diagnosis of OTFGs. Methods A total of 112 patients with surgically proven fibromas and fibrothecomas were screened consecutively from January 2016 to December 2022. Peripheral cysts were recognized in 25 patients (Group A) but were absent in the remaining 87 patients (Group B). Clinical data (including age, menopausal state, incidence of vaginal bleeding, and thickening of the endometrium) were recorded and compared between the two groups. Preoperative images of Group A and 50 matched patients with other ovarian solid and cystic tumors were combined (test group, 75 patients) and reviewed by two radiologists before and after learning about the sign. The diagnostic accuracy of OTFGs with peripheral cysts was compared. Results Preoperative imaging revealed that 22.3% (25/112) of patients with OTFGs presented with peripheral cysts. Age (56.4 ± 15.1 years vs. 43.3 ± 16.2 years, p  = 0.02), postmenopausal status (84% vs. 48%, p =  0.002), and presence of thickening of the endometrium (39% vs. 7%, p =  0.001) were significantly different between Groups A and B. The diagnostic accuracy of OTFGs was significantly improved after learning about the sign [radiologist 1, 16% (4/25) vs. 84% (21/25), p  < 0.001; radiologist 2, 32% (8/25) vs. 88% (22/25), p  < 0.001, respectively]. Conclusion The presence of peripheral cysts was not uncommon in patients with OTFGs, especially in postmenopausal patients. Familiarity with the sign could help avoid misdiagnosing solid and cystic‐like ovarian OTFGs as other ovarian solid and cystic tumors.

Association between coffee drinking and endometrial cancer risk: A meta‐analysis

AbstractAimCoffee drinking is considered as a risk factor of endometrial cancer (EC). Here, we conducted a meta‐analysis of observational study to evaluate the relationship between coffee drinking and the risk of EC.MethodsThe MEDLINE and EMBASE databases were searched until July 2018. Pooled relative risks (RRs) with 95% confidence intervals (CIs) were calculated using a random‐effects model.ResultsA total of 24 studies (12 case–control and 12 cohort studies) on coffee intake with 9833 incident cases of EC and 699 234 subjects were included in the meta‐analysis. The pooled RR of endometrial cancer for the highest versus the lowest categories of coffee intake was 0.71 (95% CI: 0.65–0.77; I2 = 14%, p for heterogeneity = 0.26). By study design, the pooled RRs were 0.68 (95% CI: 0.56–0.83) for case–control studies and 0.70 (95% CI: 0.63–0.77) for cohort studies. For different regions, the pooled RRs were 0.74 (95% CI: 0.62–0.88) in Europe, 0.71 (95% CI: 0.64–0.79) in United States/Canada, and 0.40 (95% CI: 0.28–0.57) in Japan. By additional subgroup analysis, a stronger inverse association was shown in caffeinated coffee drinkers (RR 0.66, 95% CI: 0.52–0.83), individuals with the higher body mass index (BMI) (RR 0.65, 95% CI: 0.54–0.79), never smokers (RR 0.68, 95% CI: 0.56–0.84), ever smokers (RR 0.56, 95% CI: 0.45–0.70), and those who never used hormone replacement therapy (HRT) (RR 0.88, 95% CI: 0.79–0.98). The consumption of filtered or boiled coffee showed no significant association.ConclusionsIncreased coffee intake is associated with a reduced risk of EC.

Extraskeletal myxoid chondrosarcoma mimicking mucinous ovarian cancer: A case report

AbstractPelvic masses can represent various etiologies, including gynecologic and non‐gynecologic conditions. As discussed in this paper, among all pathologies, intraabdominal dissemination of an extraskeletal myxoid chondrosarcoma (ESMC) presenting as a pelvic mass is a rare condition. The case is a 58‐year‐old woman with a history of soft tissue sarcoma who presented to the gynecologic oncology department with a pelvic mass and was operated on with the suspicion of mucinous ovarian cancer. She underwent complete cytoreductive surgery, and her final pathology was reported as ESMC. Due to several numbers of metastases shown in positron emission tomography‐computed tomography, she had chemotherapy and then operated on for tumorectomy from the right leg. ESMC is a rare, aggressive soft tissue neoplasm that rarely has metastasis to the abdomen. This unique case presents a late recurrence of the disease to the pelvis, which can mimic mucinous ovarian cancer.

Risk and survival of third primary cancers in a population‐based cohort of patients with a cervical, endometrial, or ovarian cancer

AbstractPurposeMultiple primary cancers are relevant outcomes among survivors of gynecological cancers, contributing to the overall cancer burden and having a potential impact on the management of each primary cancer. This study aimed to estimate the risk and survival of third primary cancers (TPCs) among females with a cervical, endometrial, or ovarian first primary cancer (FPC).MethodsPatients with a cervical, endometrial, or ovarian FPC from the Portuguese North Region Cancer Registry, diagnosed between 2000 and 2010 (n = 5846), were followed for a TPC (December 31, 2015) and death from any cause (December 31, 2023). The cumulative incidence of TPCs and mortality was estimated. Patients with a TPC were matched (1:1) to patients without a TPC (FPC + second primary cancer [SPC] only) to compare survival.ResultsOverall, 29 (0.5% of FPCs and 5.4% of SPCs) TPCs were diagnosed. The most common sites were digestive organs (n = 9) followed by breast and urinary tract cancers (n = 4 each). Among all FPCs, the 10‐year cumulative incidence (95% confidence interval [CI]) of a TPC was 0.5% (0.3%–0.7%) and among SPCs, it was 5.8% (3.3%–8.2%). For TPCs, compared to matched patients, the age‐adjusted hazard ratio (95% CI) for death was 3.0 (1.39–6.50). The 10‐year cumulative mortality of TPCs and matched patients was 75.7% and 42.0%, respectively.ConclusionsIn Northern Portugal, TPCs occurred mainly in digestive organs, followed by the breast and urinary tract, with a 10‐year cumulative incidence of 0.5% among all FPCs. TPCs had a worse long‐term survival compared to patients with an SPC only.

CD1a affects the recurrence and prognosis of ovarian cancer

AbstractObjectiveExplored the correlation between CD1a expression in recurrence and prognosis of ovarian cancer (OV).MethodsThe CD1a expression profile in OV, recurrent OV, and normal tissues, as well as corresponding clinical data, were obtained from The Cancer Genome Atlas (TCGA), International Cancer Genome Consortium (ICGC), Gene Expression Omnibus (GEO), and Genotype Tissue Expression (GTEx) databases. Meanwhile, immunohistochemical detection of CD1a expression in normal and OV tissues. Kaplan–Meier curves were plotted to estimate the hazard ratio (HR) of survival in OV. In addition, the correlation between CD1a and immune cells in OV, as well as the CD1a expression profile and corresponding survival time in pan‐cancer were obtained from TCGA database.ResultsCD1a was overexpressed in OV and was significantly under‐expressed in recurrent OV (TCGA‐OV, p < 0.0001 and ICGC‐OV, p < 0.0001). CD1a immunohistochemistry is significantly overexpressed in OV compared to normal tissue (p < 0.05). Recurrent OV (ICGC, p < 0.001; GSE17260, p < 0.001; GSE32062, p < 0.05). The prognosis in OV was significantly better when CD1a is overexpressed compared to under‐expressed (HR [low], 1.426: 95% confidence interval [CI], 0.912–2.128; p = 0.050). Meanwhile, the overexpression of CD1a has a better prognosis than low expression in OV and recurrent OV (p = 0.004, HR [low] = 2.462, 95%CI [1.346–4.504] and p = 0.011, HR [low] = 2.199, 95%CI [1.202–4.024]). In addition, CD1a expression was closely correlated with immune cells, the CD8+ T cells, macrophages, and NK cells, while uncharacterized cells were significantly different (p = 2.65e−6, p = 7.52e−13, p = 8.28e−12, and p = 5.89e−8, respectively). Moreover, CD1a expression affected the prognosis in various other cancers.ConclusionsCD1a expression affected the recurrence and prognosis of OV and is closely related to various immune cell levels.

Trends of minimally invasive surgery in the primary treatment of cervical cancer

AbstractMinimally invasive surgery (MIS), including laparoscopic and robot‐assisted procedures, has rapidly advanced in the treatment of gynecologic malignancies worldwide. However, its adoption and insurance coverage in AOFOG countries remain limited, particularly for advanced uterine and ovarian cancers. This limitation poses a challenge to the widespread use of MIS, highlighting the need for a more comprehensive evaluation of its role and the skills required by gynecologic oncologists to ensure safe and effective treatment. Furthermore, the Laparoscopic Approach to Cervical Cancer trial significantly impacted perceptions of MIS, revealing higher recurrence rates and inferior overall survival for minimally invasive radical hysterectomy (MIS‐RH) compared to abdominal radical hysterectomy. Subsequent studies confirmed these findings, raising questions about the suitability of MIS‐RH, particularly in centers with limited experience. Key issues affecting MIS outcomes include surgical expertise and tumor spillage prevention. As the landscape of cervical cancer treatment evolves, the integration of radiotherapy, chemotherapy, and immune therapies has challenged the traditional reliance on surgical monotherapy. There also exists ongoing debate over the optimal use of MIS in primary treatment and salvage surgery for cervical cancer to refine MIS techniques and explore their role in preserving fertility and managing residual disease post‐chemoradiotherapy. For ensuring MIS as a viable treatment option, it is continuously necessary accumulating real‐world data and reassessing surgical strategies to balance efficacy, safety, and patient preferences.

Assessment of textbook oncologic outcome after neoadjuvant chemotherapy and interval debulking surgery for advanced ovarian cancer

AbstractAimTo examine the prognostic impact of textbook oncologic outcome (TOO) in patients with advanced ovarian cancer undergoing primary chemotherapy, along with identifying the risk factors for TOO failure.MethodsPatients who underwent neoadjuvant chemotherapy followed by interval debulking surgery for advanced ovarian cancer at a tertiary center between 2014 and 2019 were retrospectively reviewed. TOO was defined as complete cytoreduction, no severe complications, no prolonged hospital stay, no readmission, no delayed initiation of adjuvant chemotherapy, and no 90‐day mortality. The associations between TOO and clinical characteristics (survival) were examined using logistic and Cox regression analyses.ResultsAmong 165 patients, 65 (39.4%) achieved TOO. The most common reason for TOO failure was incomplete cytoreduction (n = 46, 27.9%). Older age (p = 0.049) and visceral obesity (p = 0.030) were independently associated with TOO failure. Patients who achieved TOO had significantly prolonged overall survival (OS; median: 52 vs. 31 months, p = 0.010) and progression‐free survival (PFS; median: not reached vs. 19 months, p = 0.006) compared to those who did not achieve TOO. Multivariate analysis revealed that TOO achievement was an independent protective factor for OS (hazard ratio [HR] 0.591, 95% confidence interval [CI] 0.387–0.905, p = 0.015) and PFS (HR 0.626, 95% CI 0.410–0.956, p = 0.030).ConclusionsTOO is an effective predictor of favorable outcomes in patients with advanced ovarian cancer undergoing interval debulking surgery. Factors such as older age and visceral obesity may hinder the achievement of TOO.

Endometrial cancer with para‐aortic lymph node metastasis following medroxyprogesterone acetate therapy: A case report

AbstractMedroxyprogesterone acetate (MPA) is a promising fertility‐sparing treatment for early stage endometrial cancer; however, it has a high recurrence rate and is inferior to surgery. Although the site of recurrence is mostly the endometrium, we here report a case of metastatic recurrence to the para‐aortic lymph node with endometrial recurrence despite a careful follow‐up. A 31‐year‐old woman was diagnosed with grade 1 endometrioid carcinoma, stage IA without myometrial invasion. She requested fertility‐sparing treatment and underwent a 48‐week MPA therapy with complete remission. Follow‐up continued with ultrasonography and endometrial biopsy every 3 and 6 months, respectively; however, at 10 months following MPA therapy, cancer recurrence was detected in the endometrium and para‐aortic lymph node, requiring hysterectomy, bilateral adnexectomy, and lymph node dissection, followed by paclitaxel/carboplatin chemotherapy. This case report highlights that lymph node recurrence can develop despite careful follow‐up following complete remission with MPA therapy for stage IA endometrial cancer.

Uterine Smooth Muscle Tumors of Uncertain Malignant Potential ( STUMP ): Clinical Course and Follow‐Up Outcomes After Surgery

ABSTRACT Background Uterine smooth muscle tumor of uncertain malignant potential (STUMP) is a rare “gray‐zone” entity characterized by unpredictable postoperative behavior and the absence of standardized surveillance strategies. Objective To describe postoperative clinical course, recurrence patterns, and fertility‐related outcomes in patients with STUMP managed at a tertiary center. Methods We conducted a retrospective observational study including 27 patients with a final pathology diagnosis of STUMP who underwent surgery and had postoperative follow‐up available between 2009 and 2025. Clinical, surgical, and pathological variables were collected from hospital records. Recurrence was defined as radiologic evidence of a new lesion during follow‐up and categorized by anatomic site. Outcomes included recurrence status, time to recurrence, recurrence histology, subsequent management, and pregnancy outcomes after uterus‐sparing surgery. Results Median follow‐up was 58 months (IQR 17–79; range 4–136). Recurrence occurred in six patients (22.2%), with a median time to recurrence of 36 months (IQR 8–66.3). Recurrences were local ( n = 4) or pulmonary ( n = 2); one patient with lung recurrence also had wrist soft‐tissue involvement. Histology at recurrence included leiomyosarcoma ( n = 2), STUMP ( n = 2), and leiomyoma ( n = 2). All recurrent cases underwent secondary surgery. One death occurred during follow‐up. Uterus‐sparing surgery was performed in nine patients (33.3%); recurrence occurred in four, all local. Two pregnancies were recorded, including one live birth. Conclusion STUMP shows heterogeneous postoperative behavior, including late and occasionally malignant or distant recurrences. Long‐term surveillance is warranted, and uterus‐sparing management may be considered in carefully selected patients with fertility goals under close follow‐up.

LncRNA LINC00261 associates with chemoresistance and clinical prognosis in patients with epithelial ovarian cancer

AbstractObjectiveThe purpose of this experiment is to explore the role of long intergenic noncoding RNA 261 (LINC00261) gene in the chemoresistance and clinical prognosis of epithelial ovarian cancer (EOC).MethodsWe used matrix‐assisted laser desorption ionization time‐of‐flight (MALDI‐TOF) mass spectrometry to detect the methylation levels of the LINC00261 promoter region in EOC patient specimens. The expression levels of LINC00261, miR‐545‐3p, and MT1M in EOC patients were evaluated by quantitative real‐time reverse transcriptase PCR (RT‐qPCR). Spearman's correlation analysis was used for relevance analyses and clinical prognosis was counted by Kaplan–Meier analysis. Stable overexpressed LINC00261 SKOV3 cells were established to test the influence of LINC00261 on proliferation, platinum sensitivity, migration, and invasion.ResultsThe promoter region methylation level of the LINC00261 was hypermethylated and LINC00261 was significantly downregulated in platinum‐resistant EOC tissues. The methylation level of LINC00261was significantly negative correlated with its RNA expression in EOC. Moreover, hypermethylation and lower expression of LINC00261 in EOC patients were related to shorter progression‐free survival (PFS) and overall survival (OS). Furthermore, Spearman's correlation analysis showed that the expression of miR‐545‐3p had a negative relevance with LINC00261. According to the website prediction, MT1M might be the downstream target gene of LINC00261. Expression of MT1M was negatively correlated with miR‐545‐3p and positively with LINC00261 in EOC tissues. And lower MT1M mRNA expression was correlated with chemotherapy resistance and worse prognosis. In vitro, overexpression of LINC00261 could inhibit cisplatin resistance, proliferation, and suppression of migration and invasion in SKOV3 cells.ConclusionsThis research indicates that the aberrant hypermethylation and low expression of LINC00261 were associated with platinum resistance and adverse outcomes in EOC patients.

The efficacy, safety, and beneficiary population of angiogenesis inhibitor apatinib plus chemotherapy in recurrent platinum‐resistant ovarian cancer patients: A comparative cohort study

AbstractAimAngiogenesis inhibitor apatinib targets vascular endothelial growth factor receptors and improves the outcomes of patients with gynecologic malignancy. This study aimed to evaluate the efficacy and safety of angiogenesis inhibitor apatinib plus chemotherapy in recurrent platinum‐resistant ovarian cancer (RPR‐OC) patients.MethodsThis study retrieved 67 RPR‐OC patients who received apatinib plus chemotherapy or chemotherapy alone and divided them into apatinib + chemo (N = 30) and chemo alone (N = 37) groups according to the actual medication.ResultsObjective response rate (36.7% vs. 16.2%, p = 0.056) and disease control rate (80.0% vs. 59.5%, p = 0.072) showed an increased trend in apatinib + chemo group versus chemo alone group. The progression‐free survival (PFS) (p = 0.010) and overall survival (OS) (p = 0.042) were prolonged in apatinib + chemo group versus chemo alone group. The median (95%confidence interval [CI]) PFS was 5.9 (5.5–6.3) months in apatinib + chemo group and 3.8 (2.0–5.6) months in chemo alone group. The median (95%CI) OS was 20.5 (16.5–24.5) months in apatinib + chemo group and 13.6 (8.6–18.6) months in chemo alone group. Apatinib plus chemotherapy was independently related with better PFS (hazard ratio [HR]: 0.354, p < 0.001) and OS (HR: 0.116, p < 0.001). Subgroup analyses indicated that patients with a more serious disease condition might benefit more from apatinib plus chemotherapy. No difference was found in adverse events of all grade or grade ≥3 between the two groups (all p > 0.05).ConclusionAngiogenesis inhibitor apatinib plus chemotherapy shows better treatment efficacy than chemotherapy alone with controllable safety profile in RPR‐OC patients.

Endometrial cancer and endometrial changes in transgender men: Insights from Japanese individuals on testosterone

AbstractAimEndometrial changes in Japanese transgender men (TGM) on testosterone use remain elucidated. This study aims to present TGM with endometrial cancer and insights from a literature review of similar cases. Furthermore, we investigated the correlation between endometrial cancer and severe obesity in TGM who underwent gender‐affirming surgery.MethodsBetween July 2020 and April 2023, two groups were assessed: 2 TGM with endometrial cancer and 43 TGM without cancer who underwent gender‐affirming surgery. A literature review for TGM with endometrial cancer was conducted. Clinical data were retrospectively collected, and histopathological evaluation of female genital organs was performed.ResultsTwo TGM with endometrial cancer and an additional four similar cases were identified through a literature search. These TGM had severe obesity (body mass index [BMI] ≥30 kg/m2) and long‐term testosterone use, indicating a possible link between endometrial cancer and these factors. Subsequently, we investigated the 43 TGM without cancer. We revealed 30% with obesity (BMI ≥25), only three cases of severe obesity (BMI ≥30), and a significant correlation between testosterone use duration and BMI in TGM without cancer. Histological examination revealed focal proliferative endometrium in 51% of cases and polycystic ovarian changes in 77%.ConclusionsOur observations suggest a potential link between severe obesity, prolonged testosterone use, and endometrial cancer in transgender men. Histological changes in the female genital tract highlighted frequent focal proliferative endometrium, even under testosterone therapy. Further research should focus on larger, multi‐institutional studies to confirm these findings and establish endometrial cancer screening for Japanese TGM.

Oncological outcomes and risk factors for recurrence of mucinous borderline ovarian tumors: A 15‐year experience at a tertiary center

AbstractBackgroundThe most common subtype of borderline ovarian tumors in Asia is mucinous borderline ovarian tumors (mBOTs). Intraoperative distinction from mucinous carcinoma can be difficult. Despite the indolent behavior of mBOTs, recurrence or metastases may occur. The objectives of this study were to determine the oncological outcomes of mBOTs and the risk factors for their recurrence.ResultsThis retrospective study enrolled patients with mBOTs treated or referred to our institution between January 2005 and December 2019. Histological reviews of the recurrent cases (primary and recurrent or metastatic tumors) were performed. Patients with other tumor subtypes, pseudomyxoma peritonei, or no in‐house operation were excluded. Two hundred thirty‐two patients were diagnosed with mBOTs. The median follow‐up was 52 months. Six patients (2.58%) had tumor recurrence or metastasis. The risk factors for recurrence were a ruptured tumor, residual tumor after an operation, high serum CA19‐9 level, and stage of the disease. The recurrence rates of fertility‐sparing and radical surgery were not significantly different. Detailed surgical staging, intraepithelial carcinoma, and microinvasion were also not associated with disease recurrence.ConclusionsmBOTs have an excellent prognosis. Currently, fertility‐sparing surgery is the standard treatment, showing no significant difference in oncological outcomes compared to radical surgery. Patients with risk factors should be closely monitored.

Portal vein thrombosis and hepatic infarction due to hepatic mobilization after primary debulking surgery for advanced ovarian cancer: A case report

AbstractHepatic mobilization is essential in debulking surgery for resecting diaphragmatic lesions in advanced ovarian cancer. However, hepatic mobilization potentially induces postoperative portal vein thrombosis and hepatic infarction. No reports exist regarding these postoperative complications of gynecological surgeries. Thus, we reported a case of portal vein thrombosis and hepatic infarction after ovarian cancer surgery with upper abdominal surgery. The 51‐year‐old female patient who had been diagnosed with advanced ovarian and early endometrial cancer underwent primary debulking surgery. Ultimately, she underwent the following surgical procedures: a hysterectomy, bilateral salpingo‐oophorectomy, total parietal peritonectomy, low anterior resection, ileostomy, and appendicectomy. The hepatic enzymatic and D‐dimer levels were elevated, postoperatively. Contrast‐enhanced computed tomography revealed portal vein thrombosis and an infarction of the hepatic S3 region. The portal vein thrombosis resolved post‐administration of unfractionated heparin. The hepatic infarction improved. Meticulous intra‐ and postoperative management should encompass the deliberation of the potential risk of these postoperative complications.

Four cancer cases with pathological germline variant RAD51D c.270_271dup

Abstract Pathological germline variants (PGVs) of RAD51D increase the risk of breast and ovarian cancer. In East Asia, c.270_271dup is the most frequently detected PGV of RAD51D ; however, only a few cases have been reported in Japan. We report four cancer cases with a germline RAD51D c.270_271dup PGV. Three of them (lung cancer: 2, oral cancer: 1) were incidentally identified by whole genome sequencing in patients negative for the associated cancer histories, homologous recombination (HR) deficiency, or a second hit of RAD51D in the cancer DNA. For genetic counseling, we provided information on surveillance and cascade testing based on Western guidelines. The PGVs of moderate‐risk HR‐related genes are difficult to detect based on phenotype, especially in male‐predominant pedigrees. The current spread of cancer genomic analysis will increase opportunities for incidental variant identification. The establishment of Japanese guidelines is expected to aid in the management of PGV carriers of moderate‐risk genes.

Extraovarian seromucinous borderline tumor: Case report and literature review

Abstract Seromucinous borderline tumors (SMBT) are papillary neoplasms without invasive capabilities. Originally categorized as ovarian tumors, SMBT, being an endometriosis‐related tumor, can manifest beyond the ovaries. To date, only four cases of extraovarian SMBT have been documented in literature. In this report, we present our experience with the first case of SMBT in the uterine cervix, which exhibited highly elevated CA19‐9 levels. The patient, initially clinically diagnosed with cervical cancer, underwent treatment with radical hysterectomy and was later pathologically diagnosed with SMBT of the uterine cervix. While extraovarian SMBT, especially in the uterine cervix, is extremely rare, this condition should be considered in patients with cervical masses lacking pathological evidence of malignant disease but displaying elevated CA19‐9 levels.

Construction and validation of a prognostic model for overall survival time of patients with ovarian cancer by metabolism‐related genes

Abstract Background Ovarian cancer is a female‐specific malignancy with high morbidity and mortality. The metabolic reprogramming of tumor cells is closely related to the biological behavior of tumors. Methods The prognostic signature of the metabolism‐related gene (MRGs) was established by LASSO‐Cox regression analysis. The prognostic signature of MRGs was also prognosticated in each clinical subgroup. These genes were subjected to functional enrichment analysis and tissue expression exploration. Analysis of the MRG prognostic signature in terms of immune cell infiltration and antitumor drug susceptibility was also performed. Results A MRG prognostic signature including 21 genes was established and validated. Most of the 21 MRGs were expressed at different levels in ovarian cancer than in normal ovarian tissue. The enrichment analysis suggested that MRGs were involved in lipid metabolism, membrane organization, and molecular binding. The MRG prognostic signature demonstrated the predictive value of overall survival time in various clinical subgroups. The monocyte, NKT, Tgd and Tex cell scores showed differences between the groups with high‐ and low‐risk score. The antineoplastic drug analysis we performed provided information on ovarian cancer drug therapy and drug resistance. In vitro experiments verified that PLCH1 in 21 MRGs can regulate the apoptosis and proliferation of ovarian cancer cells. Conclusion This metabolism‐related prognostic signature was a potential prognostic factor in patients with ovarian cancer, demonstrating high stability and accuracy.

Update on the oncologic and obstetric outcomes of medroxyprogesterone acetate treatment for atypical endometrial hyperplasia and endometrial cancer

Abstract Aims To evaluate the safety and effectiveness of high‐dose oral medroxyprogesterone acetate (MPA) therapy as a fertility‐sparing treatment for patients diagnosed with atypical endometrial hyperplasia (AEH) and endometrioid carcinoma G1 without myometrial invasion (G1EC). Particular attention was given to the extended administration and readministration of MPA for patients with persistent disease following initial treatment and those with recurrence. Methods We conducted a retrospective analysis of data from 79 patients who underwent daily oral MPA treatment between 2005 and 2024 at Nagoya University Hospital. Patient characteristics, treatment outcomes, factors contributing to recurrence, and post‐MPA therapy pregnancies were examined. Results MPA therapy achieved a remarkable complete response (CR) rate of 91.1%. The median time to achieve CR was 26.0 and 40.0 weeks for AEH and G1EC patients, respectively. Importantly, 27 patients (39.7%) attained CR after more than 6 months of treatment, including 8 patients (11.8%) who achieved CR after more than a year of treatment. The recurrence rates were 52.9% for AEH and 64.7% for G1EC. Twenty eight patients resumed MPA treatment, and 23 achieved second CR. Notably, recurrence was not associated with clinical factors such as age, body mass index, or post‐CR pregnancy. Among patients who attempted pregnancy after achieving CR, 22 live births were successfully achieved. Conclusions High‐dose oral MPA therapy demonstrated both safety and efficacy for preserving fertility in patients with AEH and G1EC, resulting in a high CR rate. MPA extension and readministration proved to be beneficial strategies for managing patients with recurrence and persistent disease following initial treatment.

Multi‐gene panel analysis in BRCA1/2 ‐negative patients suspected of hereditary breast and ovarian cancer syndrome: Real‐world data from a single institution

Abstract Aim Although BRCA1/2 is most frequently associated with hereditary breast and ovarian cancer (HBOC), many other related genes have been implicated. Therefore, we investigated the prevalence of non‐ BRCA1/2 genes associated with hereditary cancer predisposition in BRCA1 /2‐negative patients from the Department of Genetic Medicine and Services with breast and ovarian cancer using a multi‐gene panel (MGP) analysis. Methods We conducted a retrospective MGP analysis (National Cancer Center Onco‐Panel for Familial Cancer; NOP_FC) in BRCA1/2 ‐negative patients with breast, ovarian, and overlapping breast/ovarian cancers who visited our genetic counseling between April 2004 and October 2022. Results NOP_FC was performed in 128 of the 390 BRCA test‐negative cases (117 breast cancer, 9 ovarian cancer, and 2 overlapping breast/ovarian cancer cases). Among the BRCA1/2 ‐negative patients, nine (7.7%) with breast cancer and one (11%) with ovarian cancer had pathogenic variants (PVs) in non‐ BRCA1/2 genes associated with breast and ovarian cancers, respectively. Five patients had PVs in RAD51D , two in PALB2 , one in BARD1 , one in ATM , and one in RAD51C . Conclusions Additional MGP testing of germline genes associated with hereditary cancer predisposition syndrome in BRCA1/2 ‐negative breast and ovarian cancer patients revealed PVs in non‐ BRCA1/2 breast cancer‐ and ovarian cancer‐related genes in 7.7% of breast cancer and 11% of ovarian cancer. Therefore, additional testing may provide useful information for subsequent risk‐reducing surgery and surveillance in BRCA1/2 ‐negative patients.

Knockdown of sulfotransferase 2B1 suppresses cell migration, invasion and promotes apoptosis in ovarian carcinoma cells via targeting annexin A9

AbstractBackgroundSulfotransferase family 2B member 1 (SULT2B1) has been reported to play oncogenic role in many types of cancers. Nevertheless, the role that SULT2B1 played in ovarian cancer (OC) and the hidden molecular mechanism is obscure.MethodsExpression of SULT2B1 in OC was analyzed by GEPIA database. qRT‐PCR and western blot (WB) was applied for the appraisement of SULT2B1 and Annexin A9 (ANXA9) in OC cell lines. The capabilities of cells to proliferate, migrate and invade were assessed with CCK‐8 assay, wound healing assay, along with transwell assay. Cell apoptotic level was estimated utilizing flow cytometry. WB was employed for the evaluation of migration‐ and apoptosis‐related proteins. Bioinformatic analysis and co‐immunoprecipitation were used to predict and verify the combination of SULT2B1 and ANXA9.ResultsThe data showed that SULT2B1 and ANXA9 were upregulated in OC cells. SULT2B1 depletion suppressed the proliferative, migrative, and invasive capabilities of SKOV3 cells but facilitated the cell apoptosis. SULT2B1‐regulated ANXA9 expression and were proved to bind to ANXA9. Additionally, ANXA9 deficiency exhibited the same impacts on cell migrative, invasive capability and apoptotic level as SULT2B1 silencing. Moreover, ANXA9 overexpression reversed the inhibitory impacts of SULT2B1 silencing on the proliferative, migrative, invasive, and apoptotic capabilities of SKOV3 cells.ConclusionIn summary, SULT2B1 silencing repressed OC progression by targeting ANXA9.

Ovarian fibromatosis associated with large pedunculated fibroma in a 30‐year‐old woman: A rare coincidence or variant?

AbstractA 30‐year‐old nulligravida was referred under suspicion of large subserosal myoma. T2‐weighted magnetic resonance imaging revealed multilobulated solid mass in the left lower abdomen measuring 16 cm in longitudinal diameter. The ovarian surface was covered with a marked T2‐hypointense thick rim called “black garland sign,” forming multiple nodular masses ranging from 1 to 5 cm in diameter in some portions of the bilateral ovaries. By laparoscopic‐assisted minilaparotomy, the stalk of pedunculated mass originating from the left ovarian hilum was excised, followed by carrying out of the body after in‐bag morcellation using a surgical scalpel. Right ovarian exophytic nodular masses larger than 1 cm were excised using monopolar electrode needle. Pathological examination of excised right and left masses showed fibroblast‐like spindle cell proliferation with collagenous stroma; however, differences between right and left masses cannot be distinguished on a histological level. Postoperative diagnosis was ovarian fibromatosis coexisting with large pedunculated fibroma.

Honokiol regulates ovarian cancer cell malignant behavior through YAP/TAZ pathway modulation

AbstractBackgroundOvarian cancer (OVCA) stands as one of the most fatal gynecological malignancies. Honokiol (HNK) has been substantiated by numerous studies for its anti‐tumor activity against malignancies including OVCA. Consequently, this work was designed to elucidate the impact of HNK‐mediated modulation of the YAP/TAZ pathway on the biological functions of OVCA cells.MethodsOVCA cells were subjected to treatment with varying concentrations (0, 25, 50, 75, and 100 μM) of HNK, concomitant with the administration of YAP agonist (XMU). Assessment of cellular viability was executed employing the CCK‐8 assay, while quantification of cellular proliferation transpired via colony formation assays. Apoptosis was ascertained using flow cytometry, and expression of apoptosis‐related proteins (caspase‐3, Bcl‐2, Bax), EMT‐related proteins (E‐cadherin, N‐cadherin), migration‐associated proteins (MMP‐2, MMP‐9), and YAP/TAZ pathway‐related proteins was evaluated by western blot. Transwell experiments were conducted to assess cellular migratory and invasive propensities. Xenograft tumor models were built to observe tumor growth (volume and weight), apoptosis was assessed by TUNEL staining, and Ki67 expression was evaluated through IHC.ResultsHNK exerted inhibitory effects on the viability and proliferative capacity of OVCA cells, elicited apoptotic responses, curtailed the migratory and invasive tendencies of cells, and downregulated the YAP/TAZ pathway. Stimulation with YAP agonist (XMU‐MP‐1) partially attenuated the impacts of HNK on OVCA cell biology. Experiments in vivo confirmed that HNK inhibited OVCA tumor growth.ConclusionThe outcomes of this investigation conclusively established that HNK orchestrated the modulation of the YAP/TAZ pathway, thereby exerting control over the malignant phenotypic manifestations of OVCA cells. The ascertained function of HNK in restraining cellular proliferation and tumor progression provided novel evidence of its anti‐proliferative activity within OVCA cells.

Therapy‐related myeloid neoplasms after treatment for ovarian cancer: A retrospective single‐center case series

Abstract Objective Therapy‐related myeloid neoplasms (t‐MNs) are often fatal and arise as late complications of previous anticancer drug treatment. No single‐center case series has examined t‐MNs in epithelial ovarian cancer (EOC). Methods All patients with EOC treated at Chiba University Hospital between 2000 and 2021 were included. We retrospectively analyzed the characteristics, clinical course, and outcomes of patients who developed t‐MNs. Results Among 895 cases with EOC, 814 cases were treated with anticancer drugs. The median follow‐up period was 45 months (interquartile range, 27–81) months. Ten patients (1.2%) developed t‐MNs (FIGO IIIA in one case, IIIC in three, IVA in one, and IVB in five). Nine patients were diagnosed with myelodysplastic syndrome and one with acute leukemia. One patient with myelodysplastic syndrome developed acute leukemia. The median time from the first chemotherapy administration to t‐MN onset was 42 months (range, 21–94 months), with t‐MN diagnoses resulting from pancytopenia in four cases, thrombocytopenia in three, and blast or abnormal cell morphology in four. The median number of previous treatment regimens was four (range, 1–7). Paclitaxel + carboplatin therapy was administered to all patients, gemcitabine and irinotecan combination therapy to nine, bevacizumab to eight, and olaparib to four. Six patients received chemotherapy for t‐MN. All patients died (eight cancer‐related deaths and two t‐MN‐related deaths). None of the patients was able to restart cancer treatment. The median survival time from t‐MN onset was 4 months. Conclusions Patients with EOC who developed t‐MN were unable to restart cancer treatment and had a significantly worse prognosis.

Robotic salvage radical hysterectomy for locally recurrent cervical cancer: A comparison with open surgery in a single‐surgeon series

AbstractAimTo compare the surgical and oncologic outcomes between patients with locally recurrent cervical cancer undergoing robotic‐assisted salvage radical hysterectomy (RH) and those undergoing conventional open salvage RH, performed by a single surgeon.MethodsThis retrospective comparative observational study utilized data obtained from consecutive patients with locally recurrent cervical cancer, developed after definitive radiotherapy. These patients either underwent robot‐assisted RH (robotic group) or conventional open RH (open group). Clinicopathological characteristics, surgical outcomes, and oncological outcomes were compared between the two groups.ResultsThe operative time was slightly longer in the robotic group; however, this difference was not statistically significant. Estimated blood loss was significantly lower in the robotic group (median; 0 mL [robotic group] vs. 700 mL [open group]: p < 0.01). The incidence of intraoperative and early and late complications did not statistically differ between the two groups. The mean follow‐up was 29.0 and 17.1 months in the open and robotic groups, respectively. Disease recurrence rates were similar between the two groups (40% [robotic group] vs. 44.4% [open group]). Kaplan–Meier survival analysis for progression‐free survival and overall survival did not show statistically significant differences between the two groups.ConclusionRobot‐assisted salvage RH in women with locally recurrent cervical cancer showed perioperative and oncological outcomes comparable to those of the open procedure. Although our results suggest that the robot‐assisted approach is as good as or better than the open approach, further investigation is required to establish a more robust conclusion.

Honokiol induces ferroptosis in ovarian cancer cells through the regulation of YAP by OTUB2

AbstractBackgroundOvarian cancer (OVCA) is prevalent in female reproductive organs. Despite recent advances, clinical outcomes remain poor, warranting fresh treatment avenues. Honokiol has an inhibitory effect on proliferation, invasion, and survival of cancer cells in vitro and in vivo. Therefore, this study intended to explore specific molecular mechanism by which honokiol affected OVCA progression.MethodsBioinformatics analyzed the drug honokiol that bound to OTU deubiquitinase, ubiquitin aldehyde binding 2 (OTUB2). Cellular thermal shift assay (CETSA) verified the binding relationship between honokiol and OTUB2. Cell counting kit 8 (CCK‐8) tested the IC50 value and cell viability of OVCA cells after honokiol treatment. Corresponding assay kits determined malonic dialdehyde (MDA) and Fe2+ levels in OVCA cells. Flow cytometry measured reactive oxygen species levels. Western blot detected OTUB2, SLC7A11, and transcriptional co‐activators Yes‐associated protein (YAP) expression, and quantitative polymerase chain reaction (qPCR) detected OTUB2 expression. Immunohistochemistry (IHC) detected the expression level of Ki67 protein in tumor tissues.ResultsHonokiol was capable of inducing ferroptosis in OVCA cells. CETSA confirmed that honokiol could bind to OTUB2. Further cell functional and molecular experiments revealed that honokiol induced ferroptosis in OVCA cells via repression of YAP signaling pathway through binding to OTUB2. In addition, in vivo experiments have confirmed that honokiol could inhibit the growth of OVCA.ConclusionHonokiol induced ferroptosis in OVCA cells via repression of YAP signaling pathway through binding to OTUB2, implicating that OTUB2 may be an effective target for OVCA treatment, and our study results may provide new directions for development of more effective OVCA treatment strategies.

Real‐world study of lymphadenectomy in patients with advanced epithelial ovarian cancer

AbstractBackgroundThe evidence on the role of retroperitoneal lymphadenectomy is limited to less common histology subtypes of epithelial advanced ovarian cancer.MethodsThis retrospective cohort study utilized data from the Surveillance, Epidemiology, and End Results Program from January 1, 2010, to December 31, 2019. Patients with stage III–IV epithelial ovarian cancer were included and divided into two groups based on whether they received retroperitoneal lymphadenectomy. The primary outcomes are overall survival (OS) and cause‐specific survival (CSS).ResultsAmong the 10 184 included patients, 5472 patients underwent debulking surgery with retroperitoneal lymphadenectomy, while 4712 patients only underwent debulking surgery. No differences were found in the baseline information between the two groups after propensity score matching. Retroperitoneal lymphadenectomy during debulking surgery was associated with improved 5‐year OS (43.41% vs. 37.49%, p < 0.001) and 5‐year CSS (46.43% vs. 41.79%, p < 0.001). Subgroup analysis further validate the retroperitoneal lymphadenectomy increased the 5‐year OS and CSS in patients with high‐grade serous cancer. Although the results were not validated in the less common ovarian cancer (including endometrial cancer, mucinous cancer, low‐grade serous cancer, and clear cell cancer), the tendency showed patients with the above four subtypes may benefit from the lymphadenectomy which is restricted for small sample size after propensity score matching.ConclusionsThis study revealed that retroperitoneal lymphadenectomy could further improve the survival outcome during debulking surgery in patients with advanced epithelial ovarian cancer. The conclusion was affected by the histology subtypes of ovarian cancer and further studies are needed to validate the conclusion in less common ovarian cancer.

Increase in creatinine levels associated with niraparib maintenance therapy in ovarian cancer

AbstractAimIn Japan, Niraparib maintenance therapy for primary and recurrent ovarian cancer was approved in September 2020 and is expected to improve the prognosis of ovarian cancer. However, the safety of niraparib maintenance therapy in Japanese patients has not been fully evaluated.MethodsPatients with ovarian cancer (including fallopian tube and peritoneal cancer) treated with niraparib at Jichi Medical University Hospital from September 2020 to August 2022 were enrolled in this study. Patient background, starting dose, rates of interruption, reduction, or discontinuation, adverse events (AEs) during treatment, and estimated glomerular filtration rate (eGFR) trends were retrospectively analyzed.ResultsTwenty‐nine patients received niraparib maintenance therapy during the study period, including 21 with primary cancer and 8 patients with recurrent cancer. Seventeen patients (58.6%) required dose interruptions and 16 patients (55.2%) required dose reductions. Only two patients (6.9%) discontinued treatment due to fatigue and nausea. The most frequent AE was creatinine increases in 18 patients (62.1%, all grades). Although eGFR levels decreased significantly after niraparib therapy compared to before niraparib therapy (59.3 vs. 50.3 mL/min/1.73 m2, p < 0.001), the levels returned to pre‐niraparib initiation levels after discontinuation of niraparib (64.6 vs. 64.6 mL/min/1.73 m2, p = 0.96). Multivariate regression analysis showed that diabetes was independently associated with decreased eGFR (p = 0.013).ConclusionsNiraparib maintenance therapy frequently increased serum creatinine, but the change was reversible. Further studies are needed to determine the effects of niraparib on renal function in Japanese patients.

Sertoli–Leydig tumor and DICER1 gene mutation: A case series and literature review

Abstract Objective Sertoli–Leydig cell tumors (SLCTs) are rare neoplasms occurring in young women with 60% associated with DICER1 mutations. This is only the second published case series of patients with SLCTs with associated DICER1 gene alterations. DICER1 syndrome is a rare inherited tumor‐susceptibility syndrome affecting organs such as the ovaries. We use this case series to inform readers on this increasingly important condition in gynecology. Methods and Results We present three young females presenting with secondary amenorrhoea, hirsutism, acne and in one case tonic–clonic seizures. All cases had high testosterone levels and an adnexal mass on ultrasound. Following surgical removal, pathology confirmed SLCTs and genetic testing followed. All three patients had DICER1 syndrome with two patients subsequently found to be related. Discussion The prevalence of DICER1 syndrome in the population is estimated to be 1 in 10 000 with a spectrum of sex cord stromal tumors affecting young women. The associated pathological classifications and management. This paper describes the DICER1 gene and the associated tumor predisposition syndrome alongside a surveillance protocol for use in clinical practice. It promotes discussion over the importance of early clinical genetics involvement in sex‐cord stromal tumors and the associated difficulties in counseling in a young patient population. Genetic testing and early detection are imperative for targeted surveillance of at‐risk organs to be performed but despite this there is no international guidance. The cases highlight the psychological impact of tumors in young patients and provokes an ethical discussion over DICER1 gene's inclusion in preimplantation genetics. Conclusions DICER1 syndrome is a rare but increasingly important condition in pediatric and adolescent gynecology with a paucity of published data and case reports. This makes international consensus on management and surveillance difficult.

Impact of molecular and histopathological findings on FIGO 2009 stage I endometrial cancer: Transition to FIGO 2023 staging system

Abstract Aim This study aims to investigate the impact of integrating molecular and histopathological findings into the revised International Federation of Gynecology and Obstetrics (FIGO) 2023 staging system on patients initially diagnosed with stage I endometrial cancer (EC) according to the FIGO 2009 criteria. Methods A cohort of 197 EC patients, initially classified as stage I under FIGO 2009, underwent restaging based on the updated FIGO 2023 criteria. The patients' molecular and histopathological characteristics were documented, and their impact on upstaging was analyzed. Results Molecular profiling was conducted for 81.2% (160/197) of the patients, revealing that 55.3% (109/197) were classified as non‐specific molecular profile, 14.7% (29/197) as mismatch repair deficiency, 11.2% (22/197) as p53 abnormality (p53abn), and 18.8% (37/197) as unknown. Upstaging was identified in 26.9% (43/160) of the 160 patients with known molecular profiles. Among the upstaged patients, 51.2% experienced upstaging due to p53 abnormality, 20.9% due to substantial lymphovascular space invasion (LVSI), 20.9% due to aggressive histological types, and 6.9% due to high grade. Conclusions The introduction of the molecular profile into the revised FIGO 2023 staging system for stage I EC has led to notable changes in the staging of approximately one‐fifth of patients. While p53 abnormalities have emerged as the most influential factor contributing to the upstaging, LVSI and aggressive histological types also represent significant contributing factors.

Development and validation of a nomogram for predicting specific mortality risk: A study of competing risk model based on real endometrial cancer patients

Abstract Objective This study aimed to construct a competing risk prediction model for predicting specific mortality risks in endometrial cancer patients from the SEER database based on their demographic characteristics and tumor information. Methods We collected relevant clinical data on patients with histologically confirmed endometrial cancer in the SEER database between 2010 and 2015. Univariate and multivariate competing risk models were used to analyze the risk factors for endometrial cancer‐specific death, and a predictive nomogram was constructed. C‐index and receiver operating characteristic curve (ROC) at different time points were used to verify the accuracy of the constructed nomogram. Results There were 26 109 eligible endometrial cancer patients in the training cohort and 11 189 in the validation cohort. Univariate and multivariate analyses revealed that Age, Marriage, Grade, Behav, FIGO, Size, Surgery, SurgOth, Radiation, ParaAortic_Nodes, Peritonea, N positive, DX_liver, and DX_lung were independent prognostic factors for specific mortality in endometrial cancer patients. Based on these factors, a nomogram was constructed. Internal validation showed that the nomogram had a good discriminative ability (C‐index = 0.883 [95% confidence interval [CI]: 0.881–0.884]), and the 1‐, 3‐, and 5‐year AUC values were 0.901, 0.886 and 0.874, respectively. External validation indicated similar results (C‐index = 0.883 [95%CI: 0.882–0.883]), and the 1‐, 3‐, and 5‐ AUC values were 0.908, 0.885 and 0.870, respectively. Conclusion We constructed a competing risk model to predict the specific mortality risk among endometrial cancer patients. This model has favorable accuracy and reliability and can provide a reference for the development and update of endometrial cancer prognostic risk assessment tools.

Effect of low uterine segment involvement on prognosis of early stage endometrial cancer

AbstractAimOur aim is to investigate the effect of uterine lower segment involvement on prognosis of early‐stage endometrial cancer cases diagnosed and treated in our clinic.Materials and MethodsThe file records of 316 cases reviewed retrospectively.Only stage I (a and b, n=209) cases were investigated, because they were more homogeneous group.ResultsThe lymphovascular invasion rate was found to be higher in patients with stage Ia and uterine lower segment involvement (p < 0.001). Adjuvant treatment requirement was higher in patients with stage Ia and uterine lower segment involvement (p < 0.001). Among stage Ia cases, the recurrence rate between 1 and 3 years was found to be higher in cases with uterine lower segment involvement (p = 0.001). Among the stage Ib cases, lymphovascular invasion was found to be higher in cases with uterine lower segment involvement (p < 0.001). The recurrence rate between 1 and 3 years was found to be higher in stage Ib compared to Ia (p = 0.01). Uterine lower segment involvement was found to be associated with high lymphovascular invasion rate in all stage I cases (p < 0.001). It was determined that the need for adjuvant treatment was higher in cases with uterine lower segment involvement (p < 0.001). It was determined that the probability of recurrence between 1 and 3 years was higher in cases with uterine lower segment involvement (p = 0.007).ConclusionUterine lower segment involvement is associated with increased lymphovascular invasion even in the early stages. It is an important risk factor for systemic spread such as lymphovascular invasion, myometrial invasion, and lymph node involvement.

Synchronous ovarian and uterine mesonephric‐like carcinoma that potentially arose from endometrioid adenofibroma: A case report

AbstractMesonephric‐like carcinoma histologically resembles mesonephric adenocarcinoma (MA) of the cervix. MA arises from mesonephric duct remnants. However, the origin of mesonephric‐like carcinoma is not extensively studied because of its rarity. Here, we present a case of synchronous ovarian and uterine mesonephric‐like carcinoma that potentially arose from endometrioid adenofibroma. A 69‐year‐old woman presented with an abdominal mass with no genital bleeding. She underwent simple total abdominal hysterectomy and bilateral adnexal resection. Histological and immunohistochemical analyses were consistent with mesonephric‐like carcinoma involving both ovaries and the uterus. Endometrioid adenofibroma was present in both ovaries, while adenomyosis was observed in the uterus. The glandular duct of the endometrioid adenofibroma in the right ovary had areas suggestive of precursor lesions of mesonephric‐like carcinoma. All tumors exhibited the KRAS G12D mutation. These findings suggest that the origin of the mesonephric‐like carcinoma was the Müllerian duct, and that the ovarian and uterine tumors were monoclonal.

Lenvatinib plus pembrolizumab in the patients with advanced previously treated endometrial cancer: A cost‐effectiveness analysis in the United States and in China

AbstractPurposeTo investigate the cost‐effectiveness of lenvatinib plus pembrolizumab (LP) compared to chemotherapy as a second‐line treatment for advanced endometrial cancer (EC) from the United States and Chinese payers' perspective.MethodsIn this economic evaluation, a partitioned survival model was constructed from the perspective of the United States and Chinese payers. The survival data were derived from the clinical trial (309‐KEYNOTE‐775), while costs and utility values were sourced from databases and published literature. Total costs, quality‐adjusted life years (QALYs) and incremental cost‐effectiveness ratio (ICER) were estimated. The robustness of the model was evaluated through sensitivity analyses, and price adjustment scenario analyses was also performed.ResultsBase‐case analysis indicated that LP wouldn't be cost‐effective in the United States at the WTP threshold of $200 000, with improved effectiveness of 0.75 QALYs and an additional cost of $398596.81 (ICER $531392.20). While LP was cost‐effective in China, with improved effectiveness of 0.75 QALYs and an increased overall cost of $62270.44 (ICER $83016.29). Sensitivity analyses revealed that the above results were stable. The scenario analyses results indicated that LP was cost‐effective in the United States when the prices of lenvatinib and pembrolizumab were simultaneously reduced by 61.95% ($26.5361/mg for lenvatinib and $19.1532/mg for pembrolizumab).ConclusionLP isn't cost‐effective in the patients with advanced previously treated endometrial cancer in the United States, whereas it is cost‐effective in China. The evidence‐based pricing strategy provided by this study could benefit decision‐makers in making optimal decisions and clinicians in general clinical practice. More evidence about budget impact and affordability for patients is needed.

Severe Lymphorrhea Mimicking Hypovolemic Shock Following Retroperitoneal Lymphadenectomy for Endometrial Cancer: A Case Report

ABSTRACT We present a rare case of severe lymphatic leakage resembling hypovolemic shock following retroperitoneal lymphadenectomy for endometrial cancer. A 62‐year‐old female developed massive lymphorrhea and chylous ascites following total abdominal hysterectomy, bilateral salpingo‐oophorectomy, and pelvic and para‐aortic lymphadenectomy. Immediately postoperatively, massive lymphatic leakage caused hypotension and oliguria necessitating vasopressor support. Conservative management, including fasting and octreotide, was unsuccessful. Lymphangiography with Lipiodol and subsequent embolization using N‐butyl cyanoacrylate were performed but did not achieve hemodynamic stabilization. Re‐laparotomy was undertaken, and indocyanine green injection into the bilateral inguinal lymph nodes, along with oral milk ingestion, enabled precise intraoperative identification of leakage sites. These were successfully ligated with adjunctive fibrin glue and oxidized cellulose. Hemodynamics rapidly improved following repair. Although most lymphatic leakages resolve conservatively, severe cases can cause life‐threatening circulatory failure. This case highlights the importance of a multidisciplinary approach, including interventional radiology and surgical repair, to achieve successful outcomes.

Simple radiologic assessment of visceral obesity and prediction of surgical morbidity in endometrial cancer patients undergoing laparoscopic aortic lymphadenectomy: A reliability and accuracy study

AbstractAimTo evaluate the reliability of sagittal abdominal diameter (SAD)—a surrogate of visceral obesity—in magnetic resonance imaging, and its accuracy to predict the surgical morbidity of aortic lymphadenectomy.MethodsWe conducted a multicenter reliability (phase 1) and accuracy (phase 2) cohort study in three Spanish referral hospitals. We retrospectively analyzed data from the STELLA‐2 randomized controlled trial that included high‐risk endometrial cancer patients undergoing minimally invasive surgical staging. Patients were classified into subgroups: conventional versus robotic‐assisted laparoscopy, and transperitoneal versus extraperitoneal technique. In the first phase, we measured the agreement of three SAD measurements (at the umbilicus, renal vein, and inferior mesenteric artery) and selected the most reliable one. In phase 2, we evaluated the diagnostic accuracy of SAD to predict surgical morbidity. Surgical morbidity was the main outcome measure, it was defined by a core outcome set including variables related to blood loss, operative time, surgical complications, and para‐aortic lymphadenectomy difficulty.ResultsIn phase 1, all measurements showed good inter‐rater and intra‐rater agreement. Umbilical SAD (u‐SAD) was the most reliable one. In phase 2, we included 136 patients. u‐SAD had a good diagnostic accuracy to predict surgical morbidity in patients undergoing transperitoneal laparoscopic lymphadenectomy (0.73 in ROC curve). It performed better than body mass index and other anthropometric measurements. We calculated a cut‐off point of 246 mm (sensitivity: 0.56, specificity: 0.80).Conclusionsu‐SAD is a simple, reliable, and potentially useful measurement to predict surgical morbidity in endometrial cancer patients undergoing minimally invasive surgical staging, especially when facing transperitoneal aortic lymphadenectomy.

A Novel Nomogram for Predicting Endometrial Malignancy in Postmenopausal Women

ABSTRACT Aim To identify clinical risk factors for endometrial malignancy in postmenopausal women and develop a predictive model for early detection and personalized intervention. Methods This study analyzed 1146 postmenopausal women undergoing diagnostic hysteroscopy. Inclusion required: confirmed menopause (age ≥ 40) with recent endometrial thickness measurement, successful hysteroscopy, histopathological verification, and complete records. Exclusions involved incomplete data, type II carcinoma, hormonally active tumors, or prior hysteroscopy indications. Demographics, clinical features, comorbidities, imaging data, and biomarkers were analyzed. Histology was confirmed via standard pathology. Risk factors were identified through univariate and multivariate logistic regression. The resultant predictive nomogram for endometrial malignancy risk stratification underwent rigorous validation using: (1) receiver operating characteristic curve analysis (discriminative power); (2) calibration plotting (prediction accuracy); and (3) decision curve analysis (clinical net benefit). Results Among 1146 postmenopausal women undergoing diagnostic hysteroscopy, histopathological analysis identified 69 cases (6.0%) of endometrial carcinoma (EC) and 15 cases (1.3%) of atypical endometrial hyperplasia, with the remaining cases (92.7%) demonstrating benign pathology. Multivariate analysis identified seven independent risk factors for EC: elevated fibrinogen and D‐dimer levels, hypertriglyceridemia, decreased high‐density lipoprotein, postmenopausal bleeding, ultrasonography blood‐flow signals, and increased endometrial thickness. The predictive nomogram incorporating these parameters demonstrated outstanding diagnostic performance, with area under the curve values of 0.955 in the training cohort and 0.960 in the validation cohort, indicating excellent discriminative ability for EC risk stratification. Conclusion We developed and validated a novel 7‐indicator prediction model for assessing endometrial malignancy risk in postmenopausal women undergoing hysteroscopy biopsy.

Combined Oral Contraceptives and Endometrial Cancer Among Southeast Asian Women: A Secondary Analysis of Multicenter Case–Control Study

ABSTRACT Aim To determine the association of combined oral contraceptives (COCs) use and endometrial cancer risk in Southeast Asian women. Methods This is a secondary analysis of a previously conducted multicenter case–control study with the recruitment between 2015 and 2021. Cases were women with histologically confirmed diagnoses of endometrial cancer. Controls were women admitted to different wards for other medical conditions and were individually matched to cases by age and admission date, at a ratio of three controls per case. Data regarding contraception practices were collected through interviews conducted by trained personnel using a standardized questionnaire. Conditional logistic regression models were used to calculate adjusted odds ratios (aORs) and 95% confidence intervals (CIs). Results In total, 115 (30.4%) out of 378 cases and 574 (50.6%) out of 1134 controls reported a history of COCs use. The odds of endometrial cancer were lower in women who had ever used COCs than those who reported never use (aOR 0.60; 95% CI 0.44–0.82). For every additional 12 months of COCs use, the odds of endometrial cancer decreased by 10% (aOR 0.90; 95% CI 0.86–0.93). Former COCs users had a reduced odds of endometrial cancer for up to 30 years after discontinuation (aOR 0.44; 95% CI 0.25–0.77). Conclusion A noticeable trend was observed indicating a decline in the odds of endometrial cancer with increasing duration of COCs use. COCs users continued to receive long‐term protection against endometrial cancer after discontinuation.

Successful Multidisciplinary Management of Uterine Carcinoma Treated With Chemotherapy Under Mechanical Ventilation

ABSTRACT We report a rare case of stage IVB endometrial carcinoma complicated by respiratory failure requiring mechanical ventilation. A 61‐year‐old woman with severe obesity developed bilateral pleural effusions and was admitted to the intensive care unit (ICU) for respiratory management. Because the organ failure was considered primarily tumor‐related and hepatic and renal functions were preserved, weekly paclitaxel–carboplatin chemotherapy was initiated under mechanical ventilation through close multidisciplinary collaboration. The treatment was effective, leading to improvement in the pleural effusions and oxygenation, and the patient was successfully extubated and discharged after 4 months of hospitalization. Although the disease eventually progressed, the chemotherapy administered in the ICU achieved temporary tumor control and functional recovery. This case suggests that ICU‐based chemotherapy for gynecologic malignancies, while nonstandard, may be feasible and beneficial in carefully selected patients with preserved organ function and potentially reversible, tumor‐related organ failure.

Combined Large Cell Neuroendocrine Carcinoma of the Endometrium Treated With Paclitaxel, Carboplatin, and Durvalumab, Followed by Maintenance Therapy With Durvalumab and Olaparib ( DUO ‐E Regimen): A Case Report

ABSTRACT Combined large cell neuroendocrine carcinoma (LCNEC) of the endometrium is rare and carries a poor prognosis. A 61‐year‐old woman with suspected endometrial serous carcinoma was referred to our hospital. Imaging studies staged the disease as stage IIIC1. We performed a total hysterectomy, bilateral salpingo‐oophorectomy, omentectomy, and retroperitoneal lymph node dissection. Histopathological examination revealed a combination of LCNEC, endometrioid carcinoma, and multiple lymph node metastases. Postoperative computed tomography showed multiple pulmonary metastases not detected preoperatively. Given the advanced and recurrent nature of the disease, treatment with paclitaxel, carboplatin, and durvalumab was initiated. After the first cycle, the pulmonary metastases disappeared. Maintenance therapy with durvalumab and olaparib was continued because of proficient mismatch repair status. This case demonstrates that durvalumab may be a viable treatment option for endometrial LCNEC, as it is also approved for small cell lung cancer, which shares similarities with neuroendocrine carcinoma.

Clinical translation of metabolomics markers in endometrial carcinoma

AbstractObjectiveThis comprehensive review highlights the current research on metabolomics and the metabolic pathways involved in endometrial cancer (EC), offering potential non‐invasive biomarkers for EC.MethodsThe data was extracted from published manuscripts between 2015 and 2024 using the reputed search engine “Pubmed.” All gathered data were organized into a single table, facilitating a comparison with earlier findings.ResultsThe results of this study revealed most metabolites identified in previous metabolomic research on EC are associated with lipid, glucose, and amino acid metabolism.ConclusionTherefore, understanding these metabolic pathway alterations in EC is crucial for improving diagnosis, prognosis, and treatments by specially targeting these metabolic pathways.

Successful Rechallenge With Pembrolizumab After a Grade 3 Infusion Reaction With a Far Slower Infusion Rate and Premedication: A Case Report

ABSTRACT Patients who experience grade 3 and 4 infusion reactions during pembrolizumab treatment should discontinue treatment, per the prescribing guidelines. We report a case of successful rechallenge with pembrolizumab after a grade 3 infusion reaction with a slow infusion rate and premedication. A Japanese woman in her 60s with recurrent endometrial cancer was treated using a combination of pembrolizumab and lenvatinib. During the second cycle of pembrolizumab treatment, delayed and recurrent grade 3 infusion reactions associated with systematic flushes and elevated body temperature occurred. Pembrolizumab rechallenge was performed, accompanied by the administration of premedication (histamine receptor inhibitors and acetaminophen) and reduction of the infusion rate. The flow rate was reduced to 25% of the normal rate, followed by a 50% reduction of the normal infusion rate; no recurrence of the infusion reaction was noted. Proper management of severe‐grade infusion reactions may allow the continuation of pembrolizumab treatment, thereby improving patient prognosis.

The relationship between lymph node metastasis and immunohistochemical molecular subtypes in endometrial cancer: A cohort study of 339 patients

Abstract Aim This study evaluated the association between immunohistochemically (IHC) molecular subtypes and lymph node metastasis (LNM) in endometrial cancer. Methods The study included 339 patients diagnosed with endometrial cancer (EC) confined to the uterus and treated with pelvic ± para‐aortic lymph node dissection (LND), who were included in the study. Patients were divided into two groups: LNM‐negative (Group 1, n  = 289) and LNM‐positive (Group 2, n  = 50). All patients underwent IHC‐based molecular subtype analysis. Demographic, clinical, and histopathological characteristics were evaluated. Results The median age was 62 years (34–79) in Group 1 and 64 years (48–79) in Group 2 ( p  = 0.022). Body mass index (BMI) and parity were similar between the groups ( p  > 0.05). LNM was detected in 14.7% of patients (50/339). Among Group 1, 64.4% (186/289) had a non‐specific molecular profile (NSMP), 20.1% (58/289) had mismatch repair deficiency (MMRd), and 15.5% (45/289) had the p53 abnormal (p53abn) subtype. In contrast, in Group 2, 44% (22/50) were NSMP, 24% (12/50) were MMRd, and 32% (16/50) were p53abn ( p  = 0.008). A statistically significant association was observed between LNM and the p53abn subtype. LNM was present in 26% (16/61) of patients with the p53abn subtype, compared to 17% (12/70) in the MMRd group and 11% (22/208) in the NSMP group. Conclusion While our study identified an association between the p53abn subtype and lymph node metastasis, this finding alone does not support using p53 status in isolation to determine lymphatic staging; instead, it should be considered a complementary marker alongside established clinicopathologic factors.

Surveillance of laparoscopic systemic para‐aortic lymphadenectomy for patients with intermediate‐ and high‐risk endometrial cancer in Japan

Abstract Aim To evaluate the feasibility and safety of laparoscopic systemic para‐aortic lymphadenectomy (PALN) for endometrial cancer in a multicenter setting. Methods Clinical data from 403 patients who underwent laparoscopic PALN for intermediate‐ and high‐risk endometrial cancer under Japan's advanced medical care procedure between July 2017 and March 2020 were prospectively collected. Clinical background, surgical outcome, perioperative complications, and prognosis were analyzed. Results Histological subtype was 219 (54.4%) G1 or G2 endometrioid carcinoma, 64 (15.9%) G3 endometrioid carcinoma, 64 (15.9%) serous carcinoma, 24 (6.0%) carcinosarcoma, 15 (3.7%) clear cell carcinoma, and 17 (4.2%) others. Simple hysterectomy was performed in 180 cases (44.7%) and modified radical hysterectomy (mRH) in 213 cases (52.9%). Median intraoperative blood loss was 110 mL (range: 0–2092), and 7 (1.7%) received blood transfusions. Intraoperative complications occurred in 20 cases (5.0%) including ureteral injuries (1.7%), vascular injuries (1.0%), and bowel injuries (0.5%). High‐volume facilities performing more than 15 PALN procedures harvested significantly more para‐aortic nodes than facilities performing fewer procedures. Four cases (1.0%) converted to laparotomy. Postoperative complications occurred in 53 cases (13.2%), with approximately related to lymphadenectomy. Multivariate analysis identified intraoperative blood loss, number of pelvic lymph node (PLN) removed, and radical hysterectomy (RH) as risk factors for urological complications. The number of PLNs removed and mRH were associated with lymphadenectomy‐related complications. Over a median follow‐up of 14 months (1–39), 20 patients (5.0%) experienced recurrence, and 7 (1.7%) died of the disease. Conclusion Laparoscopic PALN for intermediate‐ and high‐risk endometrial cancer could be performed safely.

Characteristic hysteroscopy appearance considerations for detecting uterine endometrial malignancies

AbstractAimThe effectiveness of hysteroscopy in diagnosing endometrial lesions has been demonstrated, showing high diagnostic accuracy for malignant endometrial lesions. Although the characteristic appearances of atypical and malignant endometria have been reported, they are not definitive and sometimes complicated. This study aimed to identify a small number of characteristic features to detect endometrial abnormalities using a simple judgment system and analyze the diagnostic characteristics and their accuracy in endometrial malignancy diagnosis.MethodsWe performed a retrospective analysis of hysteroscopy video data of 250 patients, of which we selected for analysis based on pathology examination 152 cases with benign changes, 16 with atypical endometrium, and 18 with carcinoma in situ or endometrial cancer. Endometrial characteristics assessed included protrusion, desquamation, extended vessel, atypical vessel, and white/yellow lesion.ResultsMultivariable analysis revealed that desquamation (p = 0.001, odds ratio [OR] 5.28), atypical vessels (p < 0.001, OR 8.50), and white/yellow lesions (p = 0.011, OR 1.37) were significant predictors for endometrial malignancy. From their contribution status, scoring points of 4, 6, and 1 were settled according to the odds ratio proportions. When scores ≥5 (at least both desquamation and white/yellow lesions or only atypical vessels) were used to define endometrial malignancy, sensitivity and specificity were 100% and 92%, respectively. When detecting cancer, atypical, and benign cases, sensitivity and specificity were 88% and 90%, respectively.ConclusionOur characteristics hysteroscopic findings showed a higher predictive ability in detecting endometrial malignancies. However, further examination with more cases would be needed to accurately diagnose endometrial malignancy by hysteroscopy.

Oncologic, fertility, and obstetric outcomes with MPA therapy in women with endometrial cancer and atypical endometrial hyperplasia

AbstractAimMedroxyprogesterone acetate (MPA) is one of the treatments of atypical endometrial hyperplasia (AEH) and endometrial cancer (EC) to preserve the fertility. Efficacy of MPA therapy and fertility and obstetric outcomes after remission were evaluated in EC or AEH patients.MethodsAmong patients diagnosed with EC or AEH at Tokushima University Hospital between January 2002 and October 2020, we retrospectively analyzed patients, ages range from 26 to 40, who underwent conservative management using MPA (400–600 mg/day).ResultsIn total, 19 patients underwent MPA therapy. The 18 (94%) patients achieved complete response (CR), and 1 (5%) patient achieved partial response (PR). Relapse occurred in 6 (32%) patients who had achieved CR. Of the patients who relapsed, 4 patients resumed MPA therapy and were in remission. Among 19 patients, 13 patients attempted pregnancy after CR. All of them underwent ovulation induction or assisted reproductive technology. As a result, 20 pregnancies in 10 (77%) patients and 12 live births in 9 (69%) patients were achieved. Rate of spontaneous abortion was 35% (7/20).ConclusionsMPA therapy can produce a high remission rate, and be considered an effective treatment for patients who wish fertility preservation. Around 70% patients who attempt to pregnancy can have at least one baby by infertility treatments. Because recurrence rate after MPA therapy is high, it may be desirable to aim for early pregnancy by active intervention.

D&C has the best concordance between preoperative and postoperative grades among morbidly obese endometrial cancer patients

AbstractAimEndometrial cancer is diagnosed by obtaining uterine biopsies by pipelle, dilatation and curettage (D&C), or hysteroscopy. In 15%–25% of the cases, the preoperative and postoperative grades do not match. This discrepancy may carry significant clinical and prognostic consequences. We aimed to assess how body mass index (BMI) affects preoperative and postoperative grade mismatches and whether biopsy methods mitigate this effect.MethodsWe conducted a retrospective review of patients with endometrial cancer who underwent surgery at our center between 2014 and 2022. We stratified patients into six classes of BMI based on the WHO classification. Preoperative and postoperative grades were compared for concordance with regards to patient BMI and sampling method.ResultsA total of 158 patients were included, diagnosed by pipelle (n = 99), hysteroscopy (n = 15), or D&C (n = 44). For all methods, every unit increase in BMI increased the odds of having a gap between histology grades by 5.2%. In the pipelle group, the odds of a larger gap between the histology grades was 62% higher than that of women in the other groups. Among the D&C group, the odds of having a bigger difference between histology grades were 91.8% lower compared to the other groups. Patients with BMI over 30 had nearly 50% discrepancy when diagnosed with pipelle or hysteroscopy, but less than 10% with D&C.ConclusionsIncreasing BMI is associated with decreasing concordance between preoperative and postoperative grades in endometrial cancer, especially when it exceeds 30. This effect is much less pronounced, however, when the diagnostic method is D&C.

Effects of vaginal dilation therapy on vaginal condition and sexual function of endometrial cancer patients treated with radiotherapy after surgery

AbstractObjectiveThis study aimed to evaluate the effect of vaginal dilation therapy on vaginal length, vaginal stenosis, vaginal elasticity, and sexual function of endometrial cancer patients treated with radiotherapy after surgery.MethodsA total of 117 women were enrolled in this study. They received 6 months of vaginal dilation therapy. We evaluated their vaginal length, vaginal diameter, vaginal elasticity, and sexual function before radiotherapy, after radiotherapy, and after 6 months of vaginal dilation therapy. Their vaginal condition was assessed by customized vaginal dilating molds. Their sexual function was assessed by female sexual function index. The SPSS 25 software was used to analyze all the data.ResultsAccording to multivariate analysis, vaginal diameter (β = 0.300, 95% CI [0.217–1.446], p = 0.010) and sexual intercourse frequency before diagnosis (β = 0.424, 95% CI [0.164–0.733], p = 0.006) were significantly correlated with female sexual function after radiotherapy. Vaginal dilation therapy helped increase vaginal length, improve vaginal stenosis and sexual function (p < 0.05), though most of the figures at the end of the intervention did not fully return to those before radiotherapy. Noticeably, vaginal dilation therapy was ineffective in improving vaginal elasticity and the incidence rate of female sexual dysfunction (p > 0.05). Moreover, patients with medium or good vaginal elasticity benefited more from vaginal dilation therapy than patients with poor vaginal elasticity (p < 0.05).ConclusionVaginal dilation therapy should be carried out timely and preventatively in endometrial cancer patients treated with radiotherapy after surgery to improve their vaginal condition and sexual function.

Evaluation of the usefulness of sentinel lymph node mapping using indocyanine green in patients with cervical and endometrial cancers: A single‐center prospective exploratory study

AbstractAimSentinel lymph node (SLN) mapping using indocyanine green (ICG) is an alternative for reducing comprehensive lymph node dissection and its associated morbidity. This trial aimed to assess the efficacy and safety of ICG for SLN detection in patients with cervical and endometrial cancers at a single academic teaching hospital.MethodsThis single‐arm, open‐label trial conducted at Chiba University Hospital included patients with endometrial or cervical cancer, aged 20–70 years, with an Eastern Cooperative Oncology Group performance status of 0 or 1. ICG was injected into the uterine cervix after anesthesia induction. For patients with endometrial cancer, ICG was additionally injected into the uterine myometrium after laparotomy. Imaging‐assisted surgery was then performed to locate and remove the SLNs. Systematic pelvic lymph node dissection was performed as the standard procedure, with additional para‐aortic lymph node dissection in selected cases.ResultsThe overall and bilateral SLN detection rates were 80.4% (37/46) and 50.0% (23/46), respectively. SLN identification was successful in 37 patients. Of these, 34 had pathologically negative SLNs, and all of them showed no lymph node metastasis in the backup dissection (negative predictive value: 100%). The remaining three cases had pathologically positive SLNs. No adverse events were observed in a total of 49 enrolled patients.ConclusionsICG injection was found to be safe. SLN mapping using ICG has demonstrated significant potential in reducing surgical interventions and associated complications in the treatment of early‐stage gynecological cancers.

Nomograph of cancer‐specific survival in elderly patients with endometrial cancer based on SEER database

AbstractObjectiveThis study aims to identify prognostic factors for elderly patients with endometrial cancer and to develop a nomogram for predicting cancer‐specific survival in this population.MethodsClinicopathological data of elderly patients diagnosed with endometrial cancer between 2004 and 2015 were extracted from the SEER database. Patients were randomly assigned to either a training cohort or a validation cohort at a ratio of 7:3. Univariate and multivariable Cox regression analyses were performed to identify independent prognostic factors. A nomogram was then constructed based on these factors, and its predictive accuracy and discriminative ability were assessed using the C‐index, receiver operating characteristic (ROC), and calibration curve.ResultsMultivariate analysis identified age, marital status, grade, Federation of International of Gynecology and Obstetrics, surgery, chemotherapy, radiation, and tumor size as independent prognostic factors for elderly patients with endometrial carcinoma. Nomograms derived from these factors demonstrated excellent calibration and discrimination. The C‐indexes were 0.83 for the training set and 0.82 for the validation set. The area under the curve (AUC) values for the training set were 0.88, 0.87, and 0.86 at 1, 3, and 5 year respectively. Corresponding AUC values for the validation set were 0.89, 0.86, and 0.86. Calibration curves for both cohorts demonstrated close alignment with the diagonal, indicating robust agreement between nomogram predictions and actual outcomes.ConclusionA novel nomogram has been developed for personalized prognosis assessment in elderly patients with endometrial carcinoma, aiming to enhance tailored treatment strategies and clinical management.

Three‐year questionnaire study on human papillomavirus vaccination targeting new female college school students: Follow‐up to a 2021 report to reveal the impact of a policy change in Japan

Abstract Aim The purpose of this study was to examine the trend in human papillomavirus (HPV) vaccination rates in Japan before and after a policy change in 2022, involving resumption of active recommendation and start of catch‐up vaccination. Methods From 2021 to 2023, a web‐based questionnaire survey was administered to newly enrolled female college students in Yokohama, Japan. The questionnaire included items such as age, HPV vaccination status, HPV vaccine awareness, and awareness of catch‐up vaccination. We compared knowledge about the HPV vaccine and cervical cancer in 2021 and 2023, before and after resumption of the national vaccination program. Results The HPV vaccination rates were 5.4% in 2021, 7.5% in 2022, and 35.3% in 2023, with a significant upward trend ( p  < 0.001). A similar upward trend was observed for HPV vaccine awareness (p  < 0.001). Comparing 2022 and 2023 after the start of catch‐up vaccination, there was no significant difference in awareness of catch‐up vaccination ( p  = 0.669), but there was a significant increase in awareness of free vaccination tickets ( p  < 0.001). After resumption of the national vaccination program with adoption of the catch‐up vaccination program, there was no difference in knowledge of cervical cancer, but there was a difference in knowledge of the HPV vaccine. Conclusions Although the HPV vaccination rate has increased after the policy change, it has not recovered to the level before the suspension of active recommendation. It is important for healthcare providers and school educators to actively communicate the safety and effectiveness of the HPV vaccine.

Minimally invasive surgery versus open surgery in advanced stage endometrial cancer

AbstractAimStaging surgery in early stage endometrial cancer has been shown to be feasible and safe with minimally invasive surgery (MIS) in many previous studies. However, there is limited literature on MIS's safety in advanced stages. This study aims to identify factors associated with survival in stage III endometrial cancer and investigate survival differences based on surgical approach.MethodsPatients with stage III endometrial cancer who underwent staging surgery from March 2002 to March 2023 were included in this study. Various clinicopathological features, disease‐free survival (DFS), and overall survival (OS) were evaluated.ResultsAmong the 79 patients included in this study, 20 patients underwent MIS (25.3%) and 59 patients underwent open surgery (74.7%). The open surgery group had a higher prevalence of aggressive histology, a higher median pretreatment CA‐125 level, and a greater number of harvested lymph nodes compared to the MIS group. Five‐year OS and DFS was higher in the open surgery group than in the MIS group (DFS: 67.9% vs. 59.9%, p = 0.046; OS: 74.3 vs. 50.6%, p = 0.008). In multivariate analysis, younger than 55 years old (OR, 2.778; 95% CI, 1.078–7.156; p = 0.034), and open surgery (OR, 3.671; 95% CI, 1.581–8.522; p = 0.002) was related to improved OS.ConclusionsOpen staging surgery showed better survival outcomes when compared to MIS in stage III endometrial cancer patients in our study. For patients who are older than 55 years old and have aggressive histology in endometrial biopsy, considering open surgery may help improve their prognosis, even if preoperative MRI suggests early‐stage endometrial cancer.

Data‐independent acquisition for proteomic applications in early‐stage endometrial cancer progression

AbstractAimMost endometrial cancer (EC) patients are diagnosed at an early‐stage (FIGO stage I or II), with a favorable prognosis. However, some high‐grade, early‐stage EC patients have unexpected recurrences and undesirable results, the molecular alterations that underlie these tumors are far from being fully understood. Our goal was to use proteome analysis to examine dysregulated pathways in this specific subgroup of EC.MethodsWe used data‐independent acquisition (DIA) quantitative proteomics to analyze cancer and matched paracancerous tissues from 20 EC patients (10 high‐grade and 10 low‐grade). Immunohistochemistry (IHC) analysis was used to validate protein expression of six hub genes.ResultsIn total, 7107 proteins were quantified, while 225 downregulated and 366 upregulated proteins in high‐grade cancer tissues, 130 downregulated and 413 upregulated proteins in high‐grade paracancerous tissues. The pathway associated with oxidative phosphorylation (OXPHOS) was upregulated and have similar expression patterns in high‐grade EC tissues and matched paracancerous tissues. OXPHOS‐related protein, ATP5F1D showed the best classification and diagnostic ability in distinguishing high‐grade from low‐grade EC. In both cancer and paracancerous tissues, double‐label immunofluorescence demonstrated ITGA4 and COL4A1 co‐localized at the basal membrane.ConclusionsOur present works elucidate that metabolism reprogramming is associated with high‐grade, early‐stage EC, particularly OXPHOS is upregulated. Noticeably, the paracancerous tissues have undergone molecular changes similar to cancer tissues, maybe they have signal exchange via secreted proteins (ITGA4 and COL4A1). The upregulation of OXPHOS‐related proteins may be the potential biomarker for EC diagnosis, and targeting OXPHOS metabolism might be an effective treatment for high‐grade, early‐stage EC.

Treatment outcomes of early‐stage endometrial cancer patients: A propensity score matching of vaginal brachytherapy versus pelvic radiotherapy

AbstractObjectivesThis study aimed to report the treatment outcomes of radiation therapy for early‐stage endometrial cancer patients. In addition, this study intended to identify high‐risk factors that require pelvic radiotherapy (PRT) in addition to vaginal brachytherapy (VBT) for intermediate‐risk endometrial cancer patients.MethodsPatients with early‐stage endometrial cancer receiving postoperative VBT alone or with PRT were included. Propensity score matching was used to balance the two study groups. The primary endpoint was locoregional recurrence (LRR). Age‐adjusted Charlson comorbidity index and substantial lymphovascular space invasion were selected for subgroup analyses to identify the benefits of PRT over VBT alone.ResultsFrom 2005 to 2017, a total of 288 patients underwent analysis following propensity score matching. Of these, 144 received VBT and 144 received PRT. There was no significant difference in 5‐year LRR between VBT and PRT for both intermediate (0% vs. 0%) and high‐intermediate risk patients (3.5% VBT vs. 5.4% PRT; HR 0.54: 0.05–6.00; p = 0.616). The subgroup analyses revealed no significant factors favoring PRT over VBT. Patients with high comorbidities may have higher risks of non‐cancer death after receiving PRT.ConclusionsPostoperative VBT alone is sufficient for early‐stage intermediate‐risk endometrial cancer patients.

Rate of occult atypical hyperplasia or endometrial cancer in women of older age groups with nonatypical endometrial hyperplasia (KGOG 2026)

Molecular biological analysis revealed a case of synchronous endometrial and ovarian cancer with different histological grade as metastatic ovarian cancer from endometrial cancer: Case report and review of literature

AbstractThe diagnosis of synchronous endometrial and ovarian cancer or metastatic cancer of the same histological type is difficult. In this study, molecular biology analysis was performed to determine ovarian metastasis from endometrial cancer. A 38‐year‐old woman had pathological evidence of endometrial cancer (endometrioid carcinoma, grade 1) and ovarian cancer (endometrioid carcinoma, grade 3); a disseminated nodule in the serosa uteri was also diagnosed as endometrioid carcinoma (grade 3). Customized panel sequencing revealed a common mutation pattern in ovarian cancer and disseminated nodules. Furthermore, endometrial cancer showed the same mutation patterns for FGFR3 and PTEN as ovarian cancer and disseminated nodules. All tumors were microsatellite instability high. Clinicopathological and molecular biology analyses suggested that the patient had ovarian metastasis from endometrial cancer. The patient underwent adjuvant chemotherapy with paclitaxel and carboplatin, with no recurrence. Molecular biology techniques may enable appropriate treatment based on clinically accurate diagnosis.

Do hematologic malignancies cause a barrier for sentinel lymph node mapping in endometrial cancer? A case report

AbstractSentinel lymph node (SLN) mapping has changed the way of lymph node assessment and provided a minimal invasive option that lessens the negative effects of a full lymphadenectomy, has become a crucial tool in the treatment of endometrial cancer. Chronic lymphocytic leukemia (CLL) and endometrial cancer diagnosis at the same is a rare condition. This case report presents a 66‐year‐old woman admitting to the hospital with the complaint of postmenopausal bleeding. After hysteroscopic evaluation and Magnetic Resonance imaging confirming the endometrial cancer, total laparoscopic hysterectomy and bilateral salphingo‐ooferectomy with SLN mapping operation was planned. In the preoperative preparation she was also diagnosed with CLL. Considering the possible lymphatic obstruction, the risk of SLN mapping failure was foreseen, yet still the operation was performed as planned. This report will highlight a case where endometrial cancer and CLL were identified simultaneously, along with successful SLN mapping.

SOX4 inhibits ferroptosis and promotes proliferation of endometrial cancer cells via the p53/SLC7A11 signaling

AbstractAimSex‐determining region Y‐related high‐mobility group box 4 (SOX4) has been reported to play a carcinogenic role in endometrial cancer (EC). However, the biological function and regulatory mechanisms of SOX4 in ferroptosis during the progression of EC are still unknown.MethodsThe mRNA and protein levels were scrutinized by quantitative reverse‐transcription polymerase chain reaction and western blot, respectively. The cell viability and proliferative capability were determined by cell counting kit‐8 assay and 5‐ethynyl‐2′‐deoxyuridine (EdU) assay. Transcriptional regulation of gene expression was investigated by dual‐luciferase reporter assay and chromatin immunoprecipitation. Ferroptosis was evaluated by detection of reactive oxygen species, malondialdehyde, Fe2+, and ferroptosis‐related proteins. The mice test was implemented to confirm the influence of SOX4 on EC tumor growth and ferroptosis in vivo.ResultsWe here discovered the elevation of SOX4 in EC tissues and cells. Functionally, SOX4 knockdown hampered proliferation and promoted ferroptosis of EC cells. Mechanistically, SOX4 bound to p53 promoter and inhibited its transcriptional activity in EC cells. In addition, p53 transcriptionally suppressed SLC7A11 expression in EC cells. Downregulation of p53 reverses the effect of SOX4 knockdown on proliferation and ferroptosis of EC cells. Finally, in vivo experiments demonstrated that SOX4 depletion hindered tumor growth and triggered ferroptosis in EC.ConclusionsThese findings collectively suggested that SOX4 inhibited ferroptosis and promoted proliferation of EC cells via the p53/SLC7A11 signaling. Our research unveiled a novel regulatory mechanism of ferroptosis in EC, offering promising perspectives for the development of EC therapies.

Annual report of the Committee on Gynecologic Oncology, the Japan Society of Obstetrics and Gynecology: Annual Patient Report for 2020 and Annual Treatment Report for 2015

AbstractAimTo provide information including the trend of gynecological malignancies in Japan, we hereby present the annual patient report for 2020 and the Annual Treatment Report for 2015, on the outcomes of patients who started treatment in 2015.MethodsThe Japan Society of Obstetrics and Gynecology maintains an annual tumor registry, where information on gynecological malignancies from various participating institutions is gathered. The data of patients whose treatment with gynecologic malignancies was initiated in 2020 were analyzed retrospectively. Survival of the patients who started treatment with cervical, endometrial, and ovarian cancer in 2015 was analyzed by using the Kaplan–Meier, log‐rank, and Wilcoxson tests.ResultsTreatment was initiated in 2020 for 7689 patients with cervical cancer, 13 113 with endometrial cancer, 8004 with ovarian, tubal, and peritoneal cancer, 2152 with ovarian borderline tumors, and with the others (260 vulvar cancer, 157 vaginal cancer, 464 uterine sarcoma, 50 uterine adenosarcoma, 136 trophoblastic diseases). This clinicopathological information was summarized as the patient annual report. The 5‐year survival rates of the patients with cervical cancer were 92.3%, 76.2%, 56.5%, and 32.2% for Stages I, II, III, and IV, respectively. The 5‐year survival rates for the patients with endometrial cancer were 93.9%, 87.6%, 71.4%, and 29.3% for Stages I, II, III, and IV, respectively. The 5‐year survival rates for the patients with ovarian cancer (surface epithelial‐stromal tumors) were 91.7%, 80.6%, 50.8%, and 39.7% for Stages I, II, III, and IV, respectively.ConclusionThe annual tumor report is an important survey that provides knowledge on gynecological malignancy trends in Japan.

Prospective evaluation of uterine artery Doppler for prognosis in endometrial cancer: A tertiary single‐center experience

AbstractAimsOur research aims to shed light on the connection between histopathological differences that affect the prognosis of endometrial cancer and Doppler indices measured in the uterine arteries.MethodsSeventy‐four women with a confirmed diagnosis of endometrial cancer participated in this prospective study. The flow characteristics of the bilateral uterine arteries were evaluated and recorded using color Doppler sonography. After hysterectomy, a correlation analysis was performed between these factors and histological findings.ResultsPatients who complained of menometrorrhagia had significantly higher uterine artery peak systolic flow (p = 0.020) than those who had postmenopausal vaginal bleeding. Endometrioid adenocarcinoma was the most common type (71.4%). Doppler pulsatility index and resistance index in the uterine arteries didn't show statistically significant differences between histologic subtypes, tumor grade, myometrial invasion, lymphovascular invasion, lymph node involvement, malignant peritoneal cytology, genetic mutation, or extrauterine involvement. Those without cervical involvement had higher uterine artery Doppler peak systolic flow/end diastolic flow (p = 0.024).ConclusionsEndometrial cancer made uterine artery, myometrium and endometrium less resistant to blood flow. However, these blood flow indices have not been standardized enough to be utilized as diagnostic tests just yet. Standardization based on more advanced studies would make it possible to use ultrasonography for non‐invasive diagnosis and would accelerate and facilitate clinical management.

vNOTES scarless and painless endometrial cancer staging surgery

AbstractAimsSentinel lymph node dissection is performed in endometrial cancer surgery instead of staging surgery, particularly when the disease is advanced and confined to the uterus. The aim of this study is to share our sentinel lymph node detection rates via the vaginal natural orifice transluminal endoscopic surgery method with the literature and to demonstrate a safer and more comfortable surgical treatment process.MethodsThe analysis includes the patients who underwent surgery sentinel lymph node dissection for endometrial cancer utilizing indociyanin green in our center between January 2022 and June 2024.ResultsIn all, of 24 endometrial cancer patients underwent surgery sentinel lymph node dissection, nonendometrioid (serous) pathology was observed in only 1 (4%) patient, our other patients (96%) had endometrioid adenocarcinoma pathology. The rates of our sentinel lymph node dissection bilateral and symmetric are 96% (23/24), 94% (22/24), and 79% (19/24), respectively. We would like to emphasize that we successfully used vaginal natural orifice transluminal endoscopic surgery approach on four of our patients who were unsuitable for laparoscopic and robotic surgery due to pain scores of 2 at the 12th hour after surgery and low lung capacity.ConclusionsVaginal natural orifice transluminal endoscopic surgery and sentinel lymph node dissection will be considered as surgical options in other gynecological cancers due to the comfort it brings to the patient in endometrial cancer.

Potential serum metabolites and long‐chain noncoding RNA biomarkers for endometrial cancer tissue

AbstractBackgroundEndometrial carcinoma (EC) is one of the most common tumors in the female reproductive system. There are nearly 200 000 new cases every year. It is the third most common gynecological malignant tumor leading to female death. The incidence rate is closely related to lifestyle, and the incidence rate varies in different regions. The incidence rate of EC is ranking the first in the female reproductive system cancer just second only to breast, lung, and colorectal cancer in North America and Europe and the incidence rate of EC is only second, followed by breast cancer and cervical cancer in China.PurposeThe potential metabolic markers of endometrial cancer were screened by liquid chromatograph mass spectrometer (LC‐MS), and the tissues of patients with hysteromyoma and endometrial cancer were sequenced to explore the relationship between the disease and change in the content of long‐chain noncoding RNA (lncRNA).MethodsSerum and tissue samples were collected from patients with endometrial dysplasia, endometrial cancer stage I, and endometrial cancer stage III. The metabolites in all serum samples were extracted, and the metabolites in all samples were detected by LC–MS/MS technology. The Pareto‐scaling method was used for normalization, and the MetaboAnalyst 4.0 software was used for different analyses. The T test between groups showed that p ≤ 0.05 was regarded as the metabolite with a difference. Further, the function of differential metabolites was determined by metabolite function enrichment and co‐expression analysis. Meanwhile, the differentially expressed lncRNA was detected by Illumina second‐generation high‐throughput sequencing technology, and the expression was analyzed by DEGseq software. Different lncRNA were screened according to p < 0.05. LncRNA with significant differences were screened by p < 0.01, q < 0.001, fold change ≥2, and false discovery rate (FDR) ≤0.001.ResultsThrough synthesis of T test, cluster heatmap, and ROC curve analysis, five biomarkers with potential diagnostic ability were obtained, including 2,3‐Pyridinedicarboxylic acid (area under the curve (AUC) = 0.69), Hematommic acid, ethyl ester (AUC = 0.69), Maltitol (AUC = 0.69), 13(S)‐HODE (AUC = 0.88), and D‐Mannitol (AUC = 0.69) had potential diagnostic ability between EC phase I versus EC phase III. At the same time, lncRNA sequencing results showed that when endometrial atypical hyperplasia continued to change, including LINC00511, PVT1, and IQCH‐AS1 (downregulated), and only changed significantly in the endometrial dysplasia group, including MALAT1, CARMN (downregulated) and LINC00648, BISPR, LINC01534, and LINC00930 (upregulated). Moreover, both differential metabolites and differential lncRNA were annotated to the lipid metabolism pathway, suggesting that this pathway played an important role in the occurrence and development of endometrial carcinoma.ConclusionsIt can combine the results of metabolomics and lncRNA sequencing to assist in the early diagnosis of endometrial precancerous lesions and endometrial cancer patients, to enhance the sensitivity and specificity of diagnosis, which has a certain clinical application prospect.

Incidence and characteristics of ovarian cancer following endometrial cancer in the emerging era of conservative management of endometrial cancer—Implications for counseling—A SEER analysis

AbstractObjectiveTo assess the ovarian cancer (OC) risk following endometrial cancer (EC) in patients who underwent ovarian preservation as part of the EC staging.Study DesignWith permission of the Surveillance, Epidemiology and End Results (SEER) program of the United States National Cancer Institute, clinicopathological information of women diagnosed with EC and following OC were analyzed. Incidence of OC and survival according to the surgical approach were studied. Primary analysis was conducted in women up to and including the age of 49 years.ResultsA total of 116 patients up to the age of 49 years were diagnosed with EC and following OC. In this group of patients, no differences in incidence (IRR 0.9, CI 0.56–1.49, p = 0.66) or survival rates (p = 0.71) were found comparing ovarian preservation and bilateral salpingo‐oophorectomy (BSO) performance. In an overall analysis of women diagnosed with EC and following OC at any age, incidence of OC did not differ between groups (IRR 1.07, CI 0.83–1.39, p = 0.59) yet when including patients older than 49 years old survival rates were shorter in ovarian preservation patients compared to patients with BSO performed as part of their EC treatment.ConclusionOvarian preservation in EC patients under the age of 49 years may be considered safe, with no impact on OC incidence or survival, benefiting longer natural hormonal status.

Comparison of oncological outcomes between sentinel lymph node biopsy and complete lymphadenectomy for endometrial cancer

AbstractAimSentinel lymph node (SLN) mapping allows node‐negative patients to be spared from the surgical comorbidities associated with total lymphadenectomy. This study aimed to evaluate the oncological outcomes of SLN biopsy versus complete lymph node dissection in patients with early‐stage endometrial carcinoma.MethodsRetrospective analyses were performed in patients with pathologically confirmed endometrioid endometrial carcinoma, who underwent minimally invasive surgical staging with SLN biopsy or complete lymph node dissection at Yonsei Cancer Center between 2015 and 2019.ResultsA total of 301 patients were included in this study. Eighty‐two patients underwent SLN biopsy, while 219 underwent complete lymph node dissection. There were no significant differences in patient characteristics between the two groups. In terms of operative characteristics, the SLN biopsy‐only group had a significantly shorter surgical duration (p < 0.001) than the lymphadenectomy group. The mean follow‐up period was 41.4 months. There were no differences in progression‐free survival (PFS) and overall survival (OS) between the two groups (SLN biopsy vs. complete lymph node dissection; p = 0.798 and 0.301, respectively). Multivariate analysis revealed that SLN biopsy was not an independent prognostic factor for PFS or OS.ConclusionOur results showed that SLN biopsy provided oncological outcomes similar to those of lymphadenectomy.

Application of sentinel lymph node mapping in endometrial cancer: A survey among Chinese gynecological oncologists

AbstractAimTo gain a better understanding of the use of sentinel lymph node mapping by Chinese oncologists for endometrial cancer staging and analyze factors influencing its application.MethodsQuestionnaires were collected online before and by phone after the symposium to evaluate the general characteristics of oncologists who participated in the endometrial cancer seminar and factors associated with the application of sentinel lymph node mapping in endometrial cancer patients.ResultsGynecologic oncologists from 142 medical centers participated in the survey. 35.4% of doctors employed sentinel lymph node mapping for endometrial cancer staging, 57.3% chose indocyanine green as the tracer. Multivariate analysis revealed that cancer research center (odds ratio = 4.229, 95% CI 1.747–10.237), physician familiarity with sentinel lymph node mapping (odds ratio = 126.188, 95% confidence interval 43.220–368.425) and the use of ultrastaging (odds ratio = 2.657, 95% confidence interval 1.085–6.506) were related to the doctors' selection of sentinel lymph node mapping. There was a significant difference in the surgical procedure for early endometrial cancer, the number of removed sentinel lymph node, and the reason for not adopting sentinel lymph node mapping before and after the symposium.ConclusionsThe theoretical knowledge of sentinel lymph node mapping, the use of ultrastaging, and cancer research center are related to a higher acceptance of sentinel lymph node mapping. Distance learning is conducive to the promotion of this technology.

The role of poly (ADP‐ribose) glycohydrolase in phosphatase and tensin homolog deficiency endometrial cancer

AbstractAimTo explore the relationship between poly(ADP‐ribose) glycohydrolase (PARG) and the occurrence, development, and prognosis of endometrial carcinoma (EC), and investigate whether the PARG inhibitor PDD0017273 could increase the sensitivity of EC cells to cisplatin.MethodsThe expression of PARG, phosphatase and tensin homolog (PTEN), and p53 in normal endometrial tissues (NE), endometrial hyperplasia without atypia (EH), atypical endometrial hyperplasia (AH), and EC was detected by immunohistochemistry. AN3CA EC cells with PTEN deficiency were treated with different cisplatin and PDD0017273, alone or in combination. Cell proliferation was detected by MTT method, apoptosis was detected by flow cytometry, and the expression of PARG in EC cells after treatment with different drugs was detected by western blot and immunohistochemistry.ResultsExpression of PARG in NE, EH, AH, and EC increased gradually. In addition, compared with low PARG expression in PTEN‐positive EC, patients who had high PARG expression in PTEN‐negative EC had more advanced clinical stages (r = −0.399, p = 0.032) and shorter overall survival time (p = 0.037). A dose of 40 μM PDD0017273 effectively inhibited PARG expression, increased the sensitivity of AN3CA cells to cisplatin.ConclusionsThe findings suggest that PARG overexpression is a promising immunohistochemical marker to predict the occurrence and prognosis of EC. Moreover, PARG inhibition produced antitumor effects and increased the sensitivity of EC cells with PTEN deficiency to cisplatin.

Atypical vessels in hysteroscopy: Usefulness in prediction of malignant diseases in patients treated with tamoxifen

AbstractAimTamoxifen (TAM) is widely used in adjuvant endocrine therapy for invasive breast cancer as a selective estrogen modulator, but this treatment has a risk of developing endometrial malignancy. However, hysteroscopic findings during or after TAM treatment are unclear. The aim of this study is to examine the association between hysteroscopic patterns and malignant histological findings during or after treatment with TAM.MethodsThe subjects were patients who received TAM after surgery for breast cancer and underwent hysteroscopy at our institution from January 2016 to December 2019. Clinicopathological factors and hysteroscopic findings were collected from medical records and investigated retrospectively. Histologically, atypical endometrial hyperplasia, endometrial cancer, and carcinosarcoma were classified as malignant diseases.ResultsA total of 26 patients were eligible for the study. Hysteroscopic findings included an irregular surface of the endometrium (n = 3, 11.5%), atypical vessels (n = 10, 38.5%), papillary structure (n = 3, 11.5%), and polypoid structure (n = 18, 69.2%). Histological examination revealed malignancy in six patients (23.0%). The percentage of atypical vessels in patients with malignancies was significantly higher than that in patients with a normal endometrium or benign lesion (100% vs. 20%, p = 0.0009). The sensitivity and specificity of atypical vessels in hysteroscopy for diagnosis of malignant diseases were 100% and 80%, respectively.ConclusionsHysteroscopic findings of atypical vessels may be useful for prediction of malignant diseases in patients treated with TAM.

Significance of positive peritoneal cytology for recurrence and survival in patients with endometrial cancer

AbstractAimThis study aims to examine the association between malignant peritoneal cytology and prognosis in women with endometrial cancer.MethodsWe retrospectively analyzed the records of patients with endometrial cancer who underwent surgery with intraoperative peritoneal cytology at our hospital between January 1988 and December 2012. All results were reclassified according to the 2009 International Federation of Gynecology and Obstetrics (FIGO) system, and the relation between intraoperative peritoneal cytology results and recurrence and prognosis was examined.ResultsOf the 908 patients analyzed, 205 (22.6%) had positive peritoneal cytology. Patients with positive peritoneal cytology had significantly lower rates of recurrence‐free survival (RFS) and overall survival (OS) than those in the negative cytology group (both p < 0.001). Subgroup analysis of patients with FIGO stage I/II showed significantly lower RFS in the positive‐cytology group (p = 0.005), but there was no significant difference in OS (p = 0.637). In the patients with FIGO stage III/IV or patients classified as “high risk,” the RFS and OS were significantly lower in the positive‐cytology group (both p < 0.001). Cox regression analysis identified positive peritoneal cytology as a significant predictor of recurrence in patients with FIGO stage I/II disease.ConclusionsPatients with positive peritoneal cytology for endometrial cancer have a high risk of recurrence, regardless of histopathologic type or FIGO stage. Peritoneal cytology has already been removed from the 2009 FIGO classification of endometrial cancer, but it may deserve reconsideration.

Impact of obesity on robotic‐assisted surgery in patients with stage IA endometrial cancer and a low risk of recurrence: An institutional study

AbstractAimWesternization of lifestyle has increased the numbers of patients with endometrial cancer and obesity. This study aimed to compare the clinical outcomes of robotic‐assisted surgery according to whether patients are obese, morbidly obese, or nonobese.MethodsSixty‐three patients with endometrial cancer who underwent robotic‐assisted surgery between March 2014 and June 2022 were categorized according to whether they had a body mass index (BMI) <30 (group A, nonobese, n = 40), ≥30 and <35 (group B, obese, n = 13), or ≥35 (group C, morbidly obese, n = 10). Operation time, blood loss, perioperative complications, and recurrence rate were investigated.ResultsConversion to laparotomy was required in one case in group A and one in group C. There was no difference in total operation time, time for setting (including trocar installation and docking of the da Vinci robot), console time, or time for wound closure between the groups; however, there was a significant between‐group difference in the total time for setting and wound closure. There was no significant difference in blood loss or complications between the groups. Three patients in group A and two in group B received adjuvant treatment; none have shown evidence of recurrent disease during a mean observation time of 21 months (range, 2–29). Two cases in group A and one in group B had recurrence during a mean observation time of 38 months (range, 19–46).ConclusionPatients with endometrial cancer who are obese can be treated safely by robotic‐assisted surgery with a low risk of complications and few relapses.

Safety and efficacy of levonorgestrel‐releasing intrauterine device in the treatment of atypical endometrial hyperplasia and early endometrial cancer

AbstractAimTo investigate the recurrence rate, live‐birth rate, and treatment outcomes of levonorgestrel‐releasing intrauterine device (LNG‐IUD) for the management of atypical endometrial hyperplasia (AEH) or Grade‐1 endometrial cancer (EC) in patients who desire fertility‐sparing treatment and those seeking conservative treatment without fertility preservation.MethodsWe prospectively enrolled nine patients from a single institution between April 2009 and September 2013 who were followed up for 60 months after LNG‐IUD insertion.ResultsThe median patient age was 35 (range: 29–39) years. The overall recurrence rate was 56% (5/9). The median interval between removal of the LNG‐IUD and recurrence was 20.5 (range: 2–30) months. Three of the nine patients had Grade‐1 EC, and six had AEH. The response rates to the LNG‐IUD in patients with Grade‐1 EC and AEH were 66% and 100%, respectively. Four patients (three with AEH, one with Grade‐1 EC) experienced recurrence 6 months after MPA treatment and all 4 (100%) had complete response. Eight patients desired fertility preservation, of which 37% (3/8) conceived after receiving fertility treatment and 25% (2/8) had a live birth; the remaining three had previously received MPA for 6 months and had a recurrence; of these, 1 had a live birth.ConclusionLNG‐IUD is effective for the management of AEH and EC in young patients who desire fertility‐sparing treatment, including those ineligible for MPA owing to the presence of comorbidities and those with recurrence after MPA treatment (6‐month treatment), and patients seeking conservative treatment without fertility preservation.

Prognostic values of human epididymis protein 4 expression in patients with endometrial cancer: A systematic review and meta‐analysis

AbstractBackgroundThere is no consensus on the correlation between human epididymis protein 4 (HE4) and prognosis of endometrial cancer (EC). Therefore, we performed a meta‐analysis to assess the relationship between HE4 and prognosis of EC.MethodsIn this systematic review and meta‐analysis, the databases were searched. Correlation of serum or tissue HE4 with clinicopathological characteristics was determined by odds ratio (OR) or standardized mean difference (SMD) with 95% confidence interval (CI), respectively. The hazard ratio (HR) with 95% CI was calculated to evaluate the correlation between HE4 and survival outcome.ResultsA total of 38 published studies were eligible. We found that high levels of serum HE4 were associated with FIGO III‐IV stage (SMD = 1.58, 95%CI: 1.18–1.98, p < 0.001), grade 3 (SMD = 0.66, 95%CI: 0.39–0.93, p = 0.001), ≥50% myometrial invasion (SMD = 0.78, 95%CI: 0.58–0.99, p < 0.001), lymphovascular space invasion (SMD = 0.82, 95%CI: 0.54–1.11, p = 0.001), lymph node metastasis (SMD = 1.27, 95%CI: 0.84–1.69, p < 0.001), cervical involvement (SMD = 0.71, 95%CI: 0.43–0.98, p = 0.003), parametrial involvement (SMD = 1.03, 95%CI: 0.71–1.35, p < 0.001) and peritoneal cytology (SMD = 0.49, 95%CI: 0.22–0.75, p < 0.001). High expression of tissue HE4 was only significantly associated with lymph node metastasis (OR = 6.19, 95%CI: 2.07–18.50, p = 0.001). High levels of serum HE4 were significantly associated with poor overall survival (univariate: HR = 3.77, 95%CI: 1.94–7.32, p < 0.001; multivariate: HR = 2.15, 95%CI: 1.65–2.80, p < 0.001) and disease‐free survival (univariate: HR = 2.89, 95%CI: 2.14–3.88, p < 0.001; multivariate: HR = 2.31, 95%CI:1.20–2.67, p < 0.001) in EC. Compared with cancer antigen 125, serum HE4 may be a better prognostic indicator for EC.ConclusionsHigh HE4 expression is associated with poor prognosis of EC and may be a potential prognostic biomarker for EC.

Clinicopathologic association and prognostic impact of microcystic, elongated and fragmented pattern invasion, combined with tumor budding in endometrioid endometrial cancer

AbstractAimAs a special invasive pattern seen in low‐grade endometrial carcinoma, microcystic, elongated and fragmented (MELF) pattern is related to lymph node metastasis. Tumor budding (TB) is another histological marker in many cancers associated with tumor aggressiveness. Herein, we evaluated the impact of MELF pattern combined with TB about clinicopathological features and prognosis in endometrioid endometrial cancer (EEC). To verify the relationship between the two morphological markers and microsatellite status in EEC, the primary mismatch repair (MMR) proteins were detected by immunohistochemistry.MethodsOne hundred and seventy‐two cases of ECC diagnosed between 2011 and 2016 were reviewed with a median follow up of 47.5 months. MELF pattern and TB were examined on all H&E‐stained slides. Primary MMR proteins (MLH1, MSH2, MSH6, and PMS2) were also detected.ResultsBased on MELF pattern and TB, 172 patients were divided into the following four groups: MELF(−)/TB(+) (n = 41), MELF(+)/TB(−) (n = 15), MELF(+)/TB(+) (n = 20), and MELF(−)/TB(−) (n = 96). Adverse pathological features were observed in the MELF(+)/TB(+) group: 70% presented deep muscular infiltration, 65% were lymphovascular space invasion, and 25% suffered lymph node metastasis. The proportion of MMR deficient in MELF(+)/TB(−) group was the highest (66.7%). The progression‐free survival (PFS) and overall survival (OS) among the four groups were significantly different. MELF(+)/TB(+) group showed the worst PFS and OS. As univariate and multivariate survival analyses revealed, the combination of MELF pattern and TB was confirmed as an independent predictor of poor prognosis.ConclusionsOur research demonstrates that MELF pattern combined with TB, as an independent predictor of adverse outcome, is associated with adverse pathological features, which facilitates better understanding of EEC tumor behavior and more precise prognosis without additional medical expense.

Analysis of vanishing endometrial cancer by pathological types

AbstractPurposeWe asked why endometrial cancer sometimes vanishes.MethodsA total of 454 patients diagnosed with endometrioid‐type endometrial cancer (EC) (via endometrial sampling) and treated in our clinic over the past 5 years were enrolled. The patients were divided into two groups: vanishing and residual, depending on whether a tumor was detected in the postoperative hysterectomy specimen. Patient age, numbers of pregnancies and deliveries, menopausal status, systemic disease status, hemogram parameters, International Federation of Gynecology and Obstetrics (FIGO) grade, and invasion status (evident on magnetic resonance imaging [MRI]) were compared between the groups.ResultsECs vanished in 42 (9.25%) patients. The vanishing rates were 19.7% (37/187) in FIGO grade 1 patients, 2.1% (5/238) in grade 2 patients, and 0% (0/29) in grade 3 patients. The average age was lower in the vanishing than the residual group, but the premenopausal status and grade 1 tumor rates were higher (both p < 0.001). An absence of invasion (as revealed by MRI) was more common in the vanishing group (p < 0.001). No recurrence developed in the vanishing group, but recurrences were noted in 3.3% (14/412) of the residual group. There were no significant between‐group differences in any of the numbers of pregnancies or births, systemic disease status, or hemogram parameters (all p > 0.05).ConclusionVanishing EC is more likely in premenopausal women with endometrioid grade 1 EC (as revealed by endometrial biopsy) who lack myometrial invasion on MRI.

Annual report of the committee on gynecologic oncology, the Japan Society of Obstetrics and Gynecology: Annual patient report for 2019 and annual treatment report for 2014

AbstractAimTo provide information including the trend of gynecological malignancies in Japan, we hereby present the Annual Patient Report for 2019 and the Annual Treatment Report for 2014, on the outcomes of patients who started treatment in 2014.MethodsThe Japan Society of Obstetrics and Gynecology maintains an annual tumor registry, where information on gynecological malignancies from various participating institutions is gathered. The data of patients whose treatment with gynecologic malignancies was initiated in 2019 were analyzed retrospectively. Survival of the patients who started treatment with cervical, endometrial, and ovarian cancer in 2014 was analyzed by using the Kaplan–Meier, log‐rank, and Wilcoxson tests.ResultsTreatment was initiated in 2019 for 7983 patients with cervical cancer, 12 631 with endometrial cancer, 7737 with ovarian, tubal, and peritoneal cancer, 2222 with ovarian borderline tumors, and with the others (251 vulvar cancer, 148 vaginal cancer, 476 uterine sarcoma, 43 uterine adenosarcoma, 175 trophoblastic diseases). This clinicopathological information was summarized as the Patient Annual Report. The 5‐year survival rates of the patients with cervical cancer were 92.5%, 76.8%, 58.6%, and 29.5% for stages I, II, III, and IV, respectively. The 5‐year survival rates for the patients with endometrial cancer were 94.5%, 87.3%, 70.2%, and 26.5% for stages I, II, III, and IV, respectively. The 5‐year survival rates for the patients with ovarian cancer (surface epithelial‐stromal tumors) were 90.72%, 80.4%, 53.4%, and 31.6% for stages I, II, III, and IV, respectively.ConclusionThe annual tumor report is an important survey that provides knowledge on gynecological malignancy trends in Japan.

The clinical features and management of Lynch syndrome‐associated ovarian cancer

AbstractAimLynch syndrome (LS) is one of the most common hereditary cancer syndromes, characterized by mutations in mismatch repair genes and autosomal dominant inheritance. Women with LS have an additional increased risk of gynecologic malignancies, including endometrial cancer (EC) and ovarian cancer (OC). Compared with EC, OC is relatively under investigation. This review thoroughly summarizes the current clinical evidence of surveillance, screening, and prevention strategies, and describes the molecular and clinical characteristics of LS‐associated OC.MethodsAn electronic search from databases of PubMed and Google Scholar was carried out using key words pertaining to Lynch syndrome and ovarian cancer. A review of the literatures including review articles, experimental, and observational studies published between 2000 and 2021 was conducted.ResultsThe lifetime risk of OC in women with LS of MLH1, MSH2, and MSH6 mutations is approximately 7%, with the median age at onset being 46 years, 10–15 years earlier than that in sporadic cases. Histologically, LS‐associated OCs are primarily endometrioid (40%), high‐grade (25%), and low‐grade (11%) serous, or clear cell (6%) in nature. Eighty‐five percent of patients are diagnosed at an early stage, presenting with a good prognosis at 84% 5‐year survival. Optimal screening strategies for OC in LS are controversial; combined screening of patients' clinical and family history, immunohistochemical analysis, and microsatellite instability testing for mismatch repair deficiency have been proven efficient.ConclusionThe clinical features were different between ovarian cancer in Lynch syndrome and sporadic cases. More research are needed for a greater understanding of the prevention and medical treatment of LS‐associated OC.

Adjuvant chemoradiotherapy versus chemotherapy alone in stage III endometrial cancer: A systematic review and meta‐analysis

AbstractObjectiveTo discuss the impact of chemoradiotherapy (CRT) on the survival of patients with stage III endometrial cancer (EC) compared with chemotherapy (CT) alone.MethodsArticles involving adjuvant CRT versus CT on survival in stage III EC were retrieved from PubMed and EMBASE. Hazard ratios (HRs) of overall survival (OS) and relapse‐free survival (RFS) were collected and pooled, and publication bias was measured by Begg's and Egger's test. Quality of researches was measured by the Newcastle–Ottawa scale and the modified Jadad scale.ResultsEleven were included in the statistical analysis. A significant advantage of CRT over CT on OS was shown (HR 0.59, 95% CI 0.49–0.70). Further subgroup analysis suggested the advantage was mostly associated with stage IIIC (HR 0.63, 95% CI 0.52, 0.76]). A similar result favoring CRT was also reached on RFS (HR 0.66, 95% CI 0.47–0.93). No significant publication bias was observed.ConclusionCRT was associated with a better OS and RFS than CT alone in stage III EC patients.

Expression of extracellular matrix proteins nidogen‐1 and legumain in endometrial carcinomas

AbstractPurposeOur purpose was to comparatively investigate the expressions of nidogen‐1 (NID1) and legumain (LGMN) in patients with endometrial cancer, endometrial intraepithelial neoplasia, and proliferative endometrium.MethodsA cross‐sectional, single‐center study was performed by the obstetrics and gynecology and pathology departments of our institution. The relationships between descriptive data, clinicopathologic information, and immunohistochemical expressions of NID1 and LGMN were investigated.ResultsThe histological grades of endometrial cancers (n = 124) as classified by FIGO included 1 (41, 21.1%), 2 (48, 24.7%), and 3 (35, 18.0%). The medians and ranges of deep and superficial NID1 expressions were 50.00 (0–285) and 5.00 (0–100), respectively. The intensity of legumain expression was noted as negative (30, 24.2%), mild (16, 12.9%), moderate (27, 21.8%), or strong (51, 41.1%). Median disease‐free survival and overall survival were 75.00 (range: 1 to 170) months and 77.00 (range: 1 to 170) months, respectively. Patients with more intense expression of NID1 and LGMN displayed a higher histological grade. These patients were more likely to have a positive peritoneal cytology, larger tumor size, higher tendency for myometrial or lymphovascular invasion, involvement of ovaries, cervix, omentum, as well as lymph node metastasis, and recurrence.ConclusionOur data indicated that the expressions of NID1 and LGMN may have important diagnostic implications in endometrial pathologies. Further studies should be performed to understand the significance of NID1 and LGMN in the pathogenesis of endometrial tumors.

Conservative management of grade 2 stage IA endometrial carcinoma and literature review

AbstractPurposeTo explore the clinical outcomes of megestrol acetate alone or plus metformin in young women with grade 2 stage IA endometrial carcinoma who ask for preserved fertility.MethodsPatients with stage IA grade 2 endometrial carcinoma who asked for fertility‐sparing treatment in the Obstetrics and Gynecology Hospital of Fudan University between 2015 and 2017 were enrolled and retrospectively reviewed.ResultsFour patients were included and treated with oral megestrol acetate (160 mg per day), while metformin (500 mg, thrice daily) was added for patients with metabolic syndrome. Regular hysteroscopic examination was performed every 3 months during the conservative treatment. Overall, 75% (3/4) of the patients had a complete response, one relapsed and achieved a complete response after changing the therapy plan, and one patient had an indication of myometrial invasion during fertility‐sparing treatment and chose to remove uterus.ConclusionsFertility‐sparing treatment for stage IA grade 2 endometrial carcinoma patients is worth exploration. Megestrol acetate with or without metformin combined with hysteroscopic lesion ablation may be an effective therapy.

Prophylactic ligation of uterine arteries at its origin in laparoscopic surgical staging for endometrial cancer

AbstractAimThe aim of this study was to compare the surgical outcomes between patients who were staged laparoscopically for early‐stage endometrioid‐type endometrial cancer (EC) between those who underwent prophylactic ligation of uterine arteries (UAs) prior to pelvic lymphadenectomy and the patients who were operated with standard procedure.MethodsThis retrospective study was conducted in women diagnosed with early‐stage and low/intermediate‐risk endometrioid‐type EC. The control group included patients who underwent standard laparoscopic pelvic lymphadenectomy and the study group concerned patients who underwent prophylactic ligation of UA prior to pelvic lymphadenectomy. The prophylactic ligation of UA procedure was performed at a point just proximal to its origin.ResultsThe mean lymph node count dissected in the study group was higher in terms of statistical significance (17.5 ± 2.2 vs. 19.8 ± 3.6, p = 0.003 and p ˂ 0.05). The rate of the patients who had a positive pelvic lymph node detected did not differ between groups (7.4% vs. 16.7%, p = 0.258 and p ˂ 0.05). The operation time (OT) of the patients in the study group did not differ between groups (p = 0.546 and p ˂ 0.05). Hemoglobin drop (−0.5 ± 0.7) and hematocrite drop (−0.8 ± 0.9) values in the study group were found to be lower in the study group (p = 0.000, p = 0.000, and p ˂ 0.05).ConclusionsPerforming prophylactic ligation of UA at its origin prevents unwanted bleeding and facilitates the laparoscopic pelvic lymphadenectomy procedure.

Inspection for micrometastasis is essential for predicting the prognosis of serous endometrial intraepithelial carcinoma: Case report and literature review

AbstractSerous endometrial intraepithelial carcinoma is the precursor of invasive uterine serous carcinoma. Here, we present two cases of serous endometrial intraepithelial carcinoma with omental micrometastasis and discuss their clinical significance. Two menopausal patients with abnormal endometrial biopsy findings underwent hysterectomy and comprehensive surgical staging (bilateral salpingo‐oophorectomy, omentectomy, and pelvic and para‐aortic lymphadenectomy). Although gross examination failed to detect tumors, the pathological diagnosis was serous endometrial intraepithelial carcinoma. Both patients had omental micrometastasis; they were diagnosed with International Federation of Gynecology and Obstetrics stage IVB disease and received postoperative chemotherapy. One patient died of the carcinoma 9 months after the hysterectomy, and the other had a recurrence of carcinoma 17 months after the end of the initial therapy. The present cases and literature review highlight the importance of meticulous inspection for micrometastasis in the abdominal cavity, including the omentum and peritoneum, for predicting prognosis.

Achievement of live birth after overcoming two gynecological malignancies treated with radical trachelectomy and medroxyprogesterone acetate therapy

AbstractCervical cancer is a human papilloma virus‐related disease, whereas endometrial cancer and atypical endometrial hyperplasia (AEH) are hormone‐related diseases, so co‐occurrence of the two is possible. However, scientific studies about such cases are rare. We encountered a case of cervical adenocarcinoma and AEH in a 33‐year‐old nulliparous woman. Two fertility‐sparing treatments were performed, a radical trachelectomy for the cervical cancer and high‐dose medroxyprogesterone acetate treatment for the AEH. After remission of the diseases, the patient became pregnant by in vitro fertilization and delivered a baby at 36 weeks' gestation by cesarean section. Although the patient had two uterine malignancies, proper evaluation of the diseases, consultation with the patient and her husband, and appropriate management led to fertility preservation, and live birth was achieved.

Prognostic significance of tumor budding, poorly differentiated cluster, and desmoplastic reaction in endometrioid endometrial carcinomas

AbstractAimsThe tumor budding (TB); poorly differentiated cluster (PDC); desmoplastic reaction (DR); and microcystic, elongated, and fragmented (MELF) patterns of invasion are pathological findings at the tumor invasion front associated with epithelial‐to‐mesenchymal transition. This study aimed to clarify the clinical significance of the TB, PDC, DR, and MELF patterns in endometrioid endometrial carcinomas (EEC).MethodsTwo hundred and eight cases of histologically proven EEC retrieved from the archives of the Department of Pathology, Fukui Prefectural Hospital, and diagnosed between January 2000 and August 2020 were retrospectively analyzed.ResultsThe TB, PDC, DR, and MELF patterns were identified in 29 (13.9%), 47 (22.6%), 45 (21.6%), and 23 (11.1%) cases, respectively. Kaplan–Meier curve analysis with log‐rank test demonstrated that TB, PDC, and DR were associated with a lower progression‐free survival (p = 0.010, 0.002, and <0.0001, respectively), whereas the MELF pattern did not show any association (p = 0.668). In multivariate analyses, only DR was significantly associated with lower progression‐free survival (p = 0.034). Moreover, only PDC was associated with lower overall survival in univariate analysis (p = 0.018), but the association lost significance in multivariate analysis.ConclusionsThe present study revealed that the histological confirmation of TB, PDC, and DR at the tumor invasive front predicts poor prognosis in EEC. However, the MELF pattern was not a predictor of poor prognosis in EEC.

Dipeptidyl peptidase IV is required for endometrial carcinoma cell proliferation and tumorigenesis via the IL‐6/STAT3 pathway

AbstractAimTo study the functions and signaling pathways controlled by dipeptidyl peptidase IV (DPPIV) in endometrial carcinoma (EC).MethodsDPPIV expression in EC cells was detected by flow cytometry, reverse transcription‐polymerase chain reaction analysis and Western blot. Interleukin‐6 (IL‐6) expression in the supernatant was measured by enzyme‐linked immunosorbent assay. The protein levels of signal transducers and activators of transcription‐3 (STAT3), phosphorylate STAT3, cellular Myc, and vascular endothelial growth factor in EC cells were measured by Western blot. Colony formation assays were used to assess the clonogenicity of EC cells. Ki67 immunostaining and cell counting were used to test the proliferative ability of EC cells. Nude mouse tumorigenicity assay was used to confirm DPPIV promotes the tumorigenicity of EC cells. A cell counting kit‐8 assay was used to determine the half‐maximal inhibitory concentration of sitagliptin.ResultsOverexpression of DPPIV in EC cells with low DPPIV expression promoted cell proliferation in vitro (p < 0.01) and enhanced tumorigenicity in vivo (p < 0.05). Conversely, knocking down DPPIV expression in EC cells with high DPPIV expression inhibited cell proliferation (p < 0.01) and in vivo tumorigenicity (p < 0.01). DPPIV promoted EC cell proliferation via activation of IL‐6/STAT3 signaling pathway, and that IL‐6 could trigger a positive feedback loop that increased DPPIV expression (p < 0.01). Furthermore, the DPPIV inhibitor reduced STAT3 expression (p < 0.01) and inhibited growth of EC cells (p < 0.001).ConclusionDPPIV enhances the properties that allow tumorigenesis in EC via IL‐6 and STAT3 signaling.

Knockdown of long non‐coding RNA small nucleolar RNA host gene 9 or hexokinase 2 both suppress endometrial cancer cell proliferation and glycolysis

AbstractAimEndometrial cancer (EC) is a common type of malignant gynecological cancer. Small nucleolar RNA host gene 9 (SNHG9) has been discovered to serve a role in several types of cancer; however, the role of SNHG9 in EC remains unclear. The present study aimed to investigate the effects of lncRNA SNHG9 on cell proliferation and glycolysis in EC cells.MethodsSNHG9 and hexokinase 2 (HK2) mRNA expression levels were measured by reverse transcription‐quantitative PCR. Glucose consumption and lactate production were detected by the glycolysis cell‐based assay kit. Cell Counting Kit‐8 and colony formation assays were conducted to detect cell proliferation. The knockdown experiments of SNHG9 and HK2 were carried out by transfection of corresponding small interference RNAs (siRNA). The SNHG9‐overexpressed plasmid was transfected into the cells to upregulate SNHG9. HK2 protein levels were analyzed by western blotting assay.ResultsSNHG9 expression levels were significantly upregulated in EC tissues and cells. The knockdown of SNHG9 subsequently effectively attenuated cell proliferation and glycolysis in vitro, while SNHG9 overexpression reported the opposite effects. Notably, the transfection of 2‐DG partially reversed the promoting effect of SNHG9 on glycolysis. Downregulation of HK2 markedly decreased cell proliferation and glycolysis in EC cells antagonized SNHG9.ConclusionEither downregulation of SNHG9 or HK2 inhibits EC cell proliferation and glycolysis via repressing EC cell proliferation and glycolysis.

ES Sampler, a minimally invasive endometrial sampling tool that obtains specimens suitable for both cytological and histological analysis

AbstractAimConventional endometrial examination by dilatation and curettage (D&C) is not accepted by many patients because it is associated with pain and risk of injury and typically requires anesthesia and hospitalization. While several less invasive endometrial screening tools have been developed, their diagnostic value is generally inferior to D&C. Therefore, the purpose of this study was to evaluate the effectiveness of a new, minimally invasive device, called the ES Sampler, for outpatient endometrial screening.MethodsThis was a single‐blind study of 96 patients (age: 36.8 ± 8.1 years) who attended Peking Union Medical College Hospital from March 2015 to August 2016. Specimens were collected from each participant using the ES Sampler, followed by traditional D&C by hysteroscopy, and evaluated by histology and/or cytology. The sampling adequacy, sensitivity, specificity, positive and negative predictive value, and diagnostic accuracy were compared, and patient acceptability was assessed.ResultsCompared to traditional D&C, the ES Sampler exhibited 99.0% sampling adequacy, and the combined (histology and cytology) results demonstrated 88.9% sensitivity, 95.6% specificity, 88.9% positive predictive value, 95.6% negative predictive value, and 93.7% accuracy. Moreover, the majority of study participants reported mild or no pain associated with the ES Sampler, and blood loss was minimal.ConclusionsOur findings suggest that the minimally invasive ES Sampler is a reliable and accurate endometrial screening tool that is easily accepted by patients. The ES Sampler could be useful for screening high‐risk patients who may need further, more invasive examination, thereby conserving medical resources and minimizing patient discomfort.

Establishment and evaluation of a risk‐scoring system for lymph node metastasis in early‐stage endometrial carcinoma: Achieving preoperative risk stratification

AbstractAimTo establish a risk‐scoring system for lymph node metastasis (LNM) of early‐stage endometrial carcinoma (EC), and to stratify the preoperative risk of LNM.MethodsWe retrospectively analyzed the clinical data of 507 patients diagnosed with the early‐stage EC (i.e., confined to the uterine corpus). We determined the risk factors for LNM by logistic regression analysis; then constructed a simple logistic scoring system, and an additive scoring system based on the regression coefficient (β), and odds ratio, of each variable, respectively.ResultsThe overall rate of LNM was 9.1% (46/507). Multivariate analysis showed that preoperative serum cancer antigen 125 (CA125) ≥35 U/mL, histopathology of grade 3 and/or type II, depth of myometrial invasion ≥1/2 and positive immunostaining for Ki‐67 ≥50%, were independent risk factors for LNM (P < 0.05). The simple logistic and additive scoring systems exhibited good predictive ability (area under the curve [AUC] >0.8). Based on the additive scoring system, the risk of LNM in patients with early‐stage EC was classified into three groups: a low‐risk group (total score: <5), an intermediate‐risk group (total score: 5–10) and a high‐risk group (total score: >10). The incidence of LNM differed significantly across these three groups (P < 0.05).ConclusionThe risk‐scoring system constructed in this study can effectively predict the risk of LNM in patients with early‐stage EC, achieve preoperative risk stratification and provide a reference guideline for the use of lymphadenectomy.

The evaluation of laparotomy results in breast cancer patients with gynecological pathologies

AbstractAimThe aim of the study was to evaluate the results of the laparotomies due to gynecological pathologies in breast cancer patients and to assess the distribution of gynecological pathologies and the clinical and laboratory findings contributing to the diagnosis.MethodsThis study was conducted between years 2002 and 2011 at Hacettepe University Hospital. We obtained information about 86 consecutive breast cancer patients, including age, time of diagnosis and pathology of breast cancer, hormone receptor status, history of endocrine therapy, presenting symptoms, ultrasonography findings, CA 125 levels, endometrial biopsy results, type of gynecological surgery and pathology results. Data were analyzed with the use of SPSS software.ResultsTwenty‐one (24.4%) out of 86 patients had endometrial pathology, and 24 (27.9%) had adnexal pathology. Fourteen patients (16.2%) had malignant pathology, and of them, 11 had ovarian cancer 3 had endometrial cancer. There were five abnormal cytological findings: 2 ASCUS, 1 LSIL, 1 ASC‐H and 1 adenocarcinoma. The patient with the cytology report of adenocarcinoma had the final diagnosis of endometrial cancer. Of the patients, 67 (77.9%) used tamoxifen, whereas 19 (22.1%) did not. Thirty‐three patients (38.4%) with gynecological pathologies were detected incidentally during routine follow‐up of breast cancer.ConclusionThis study supports the increase of the gynecological pathology incidence in breast cancer patients and the recommendation of close gynecological follow‐up in these patients. Asymptomatic patients might also develop genital cancer. The ultrasonographic appearance of the adnexal masses or endometrial thickness and any abnormal vaginal bleeding or high CA 125 levels are important parameters for evaluating breast cancer patients.

Endometrial cancer patients have high affinity antibodies for estrogen metabolite–receptor aggregate: A potential biomarker for EC

AbstractAimElevated levels of 16α‐hydroxyestrone (16α‐OHE1) have been described in endometrial cancer (EC) and estrogen receptors (ER) expressed in endometrial tissue, but research on their combined role is lacking. We aimed to investigate the affinity and binding specificity of EC antibodies against the 16α‐OHE1‐ERα aggregate in the serum of EC patients. Specificities of EC antibodies were also evaluated according to various clinical characteristics found in these cancer patients.MethodsThe binding specificity and affinity of EC antibodies against 16α‐OHE1‐ERα in the serum of 120 EC patients were evaluated by direct binding and competition ELISA and quantitative precipitation titration. Binding of EC antibodies was also determined according to various clinical characteristics in EC patients through competition ELISA.ResultsAntibodies from EC patients demonstrated high recognition of 16α‐OHE1‐ERα compared to ERα (P < 0.05) or 16α‐OHE1 (P < 0.001). The relative affinity of EC IgG was 1.49 × 10−7 M, 1.34 × 10−6 M and 1.13 × 10−6 M for 16α‐OHE1‐ERα, ERα and 16α‐OHE1, respectively. Several factors, such as obesity, postmenopausal status, use of hormonal therapy, ER and progesterone receptor (PR) status, low 2‐OHE1/16α‐OHE1 ratio, chemotherapy and hypertension, augment the production of antibodies against 16α‐OHE1‐ERα in EC patients.Conclusion16α‐OHE1‐ERα is a high‐affinity antigen for EC antibodies in the serum of EC patients and might function as a biomarker for this disease. Furthermore, several factors enhanced the production of antibodies against 16α‐OHE1‐ERα in the sera of these EC patients.

Can preoperative inflammatory markers differentiate endometrial cancer from complex atypical hyperplasia/endometrial intraepithelial neoplasia?

AbstractAimThe aim of this study was to identify the differences between complex atypical hyperplasia/endometrial intraepithelial neoplasia (CAH/EIN) and endometrioid‐type grade 1 endometrial cancer in terms of preoperative systemic inflammatory markers and to evaluate the effectiveness of such markers in predicting cancer.MethodsBetween January 2005 and September 2018, a total of 372 patients with final histopathologic diagnoses of CAH/EIN (n = 143) and endometrioid‐type grade 1 endometrial cancer (n = 229) were included in the study. Neutrophil/lymphocyte ratio (NLR), platelet/lymphocyte ratio (PLR) and platelet distribution width (PDW) were used as preoperative inflammatory markers. Receiver operating characteristics (ROC) analysis was used to assess the diagnostic prediction of NLR, PLR and PDW values to distinguish the two groups. Univariate and multivariate logistic regression analysis was performed by regrouping the patients according to the cut‐off values found in the ROC analysis.ResultsThe univariate analysis revealed that advanced age, decreases in PDW and also PLR could be predictors of cancer. The cut‐off values were as ≤48.9% for PDW and ≤133.3 for PLR. The values defined using ROC analysis were found to be statistically significant for PDW and PLR in identifying endometrioid grade 1 endometrial cancer. For PDW, sensitivity, specificity, positive predictive value and negative predictive value were 52.8%, 62.2%, 68.9% and 45.5%, respectively (P = 0.001); for PLR, those were 55.9%, 59.4%, 68.8% and 45.7%, respectively (P = 0.005). In multivariate analysis, advanced age (>53 years), low PDW (≤48.9%) and low PLR (≤133.3) were related to statistically significant odds ratio for diagnostic prediction to differentiate endometrioid grade 1 cases from CAH/EIN of 8.01 (P < 0.001), 1.79 (P = 0.019) and 1.73 (P = 0.025), respectively.ConclusionsThe PLR and PDW values in the preoperative blood parameters could be used to differentiate endometrial cancer from precancerous lesions.

Short‐term outcomes of robot‐assisted versus conventional laparoscopic surgery for early‐stage endometrial cancer: A retrospective, single‐center study

AbstractAimWe compared the short‐term outcomes between conventional laparoscopic surgery (CLS) and robot‐assisted surgery (RAS) to assess the technical feasibility of the latter for early‐stage endometrial cancer.MethodsWe retrospectively compared the perioperative outcomes between two groups of 223 patients (CLS group, n = 102; RAS group, n = 121) with early‐stage endometrial cancer. Surgical procedures included hysterectomy, bilateral salpingo‐oophorectomy and retroperitoneal lymphadenectomy. We analyzed the data from intrapelvic surgery alone because para‐aortic lymphadenectomy was performed via conventional endoscopic extraperitoneal approach without robot for both groups.ResultsNo differences were identified in patients' age and body mass index. The mean operative time was 133 ± 28 versus 178 ± 41 min (P < 0.01), mean blood loss was 196 ± 153 versus 237 ± 146 mL (P = 0.047), mean length of postoperative hospital stay was 9 ± 4 versus 8 ± 3 days (P = 0.01) and mean rate of perioperative complications of Clavien‐Dindo grade III or higher was 2.0 versus 3.4% (P = 0.53) for the CLS versus RAS groups, respectively. There was no significant difference in the number of resected lymph nodes.ConclusionThe operative time was significantly longer and blood loss was significantly greater in the RAS group than in the CLS group, without a significant difference in the number of resected lymph nodes. These differences are within an acceptable clinical range, showing that RAS is feasible and safe for early‐stage endometrial cancer, providing short‐term outcomes comparable to those of conventional surgery. Future studies are warranted to compare the long‐term oncological outcomes by extending the observation period and including para‐aortic lymphadenectomy data.

Cancers associated with extraovarian endometriosis at less common/rare sites: A nationwide survey in Japan

AbstractAimEndometriosis mostly affects the ovary but can also be present outside of the ovary including the pelvic peritoneum, intestine, urinary tract and lung. In case of ovarian endometriotic cyst, an increased risk of ovarian cancer, especially of clear cell and endometrioid histology, has been reported. However, because of the rarity, cancer occurrence from endometriosis at less common sites/rare sites is poorly understood.MethodsWe conducted a nationwide survey on the less common/rare site endometriosis in 3539 authorized facilities in Japan. We requested to complete a case report form for each case, including information on the history of endometriosis, treatment for endometriosis, type of surgery, involved site(s) of cancer and endometriosis, histology of cancer, chemotherapy and outcome.ResultsOut of 1397 confirmed cases of less common/rare site endometriosis, 11 cases of rare site endometriosis‐associated cancer (RSEAC) were reported: seven of them were associated with intestinal endometriosis, three were associated with urinary tract endometriosis and one was associated with umbilical endometriosis. Interestingly, the histology was endometrioid in seven (64%) cases, and serous, seromucinous borderline, clear cell and mucinous in one case each (10%), differing from the case of ovarian endometriosis‐associated cancer, in which clear cell carcinoma are more common.ConclusionOur nationwide survey on RSEAC has revealed that: (i) the incidence of malignant transformation may be lower than ovarian endometriosis, (ii) malignant transformation from endometriosis outside the abdominal cavity may be extremely rare and (iii) the histology of RSEAC is predominantly endometrioid type, suggesting an association of a hormonal effect.

Prevalence of venous thromboembolism at pretreatment screening and associated risk factors in 2086 patients with gynecological cancer

AbstractAimPostoperative pulmonary embolism can be a fatal surgical complication and is thought to occur secondary to asymptomatic venous thromboembolism (VTE) that exists preoperatively in some patients. The purpose of this study was to clarify the frequency and risk factors of pretreatment VTE in gynecological cancer patients.MethodsThis study investigated 2086 patients with gynecological cancer (cervix, n = 754; endometrium, n = 862; ovary, n = 470) who underwent initial treatment between 2004 and 2017. Pretreatment VTE screening was performed with D‐dimer (DD) levels in these patients. Based on this, the associated risk factors were retrospectively analyzed.ResultsPretreatment VTE was discovered in 7.3% of patients with cervical cancer, 11.5% of those with endometrial cancer and 27.0% of those with ovarian cancer. Significant independent risk factors were: age greater than or equal to 60 years and tumor long diameter greater than or equal to 40 mm for cervical cancer; age greater than or equal to 60 years, stage III/IV advanced disease, clear cell carcinoma and tumor long diameter greater than or equal to 60 mm for endometrial cancer; and age greater than or equal to 60 years, clear cell carcinoma and massive ascites for ovarian cancer.ConclusionPretreatment asymptomatic VTE is very frequent in gynecological cancer patients. It may be beneficial to consider measuring DD or performing venous ultrasonography in patients with the above risk factors.

A risk nomogram for assessing complications in patients undergoing surgical procedures for cervical cancer. Does baseline quality of life play a role?

AbstractObjectiveSurgery for cervical cancer is a known risk factor for hospital readmission, often due to urological, lymphovascular, or neurological complications. While comorbidities are commonly used to assess surgical risk, patient‐reported measures like baseline quality of life (QoL) may also help predict complications. This study aimed to estimate how often surgical complications occur and what factors predict them, with a focus on baseline QoL.MethodsWe conducted a prospective observational study of 100 cervical cancer patients who had surgery at a tertiary hospital between January 2010 and January 2019. A binary logistic regression model was used to predict surgical complications. Baseline QoL was measured with the Functional Assessment Cancer Therapy‐cervix questionnaire. Data were analyzed using R software.ResultsSurgical complications occurred in 54% of patients, most of them after surgery. There was no significant difference in QoL scores between patients with and without complications (p = 0.753). The prediction model showed good calibration (Hosmer–Lemeshow p = 0.999), no multicollinearity (variance inflation factor = 1.01), and moderate accuracy (C‐index = 0.67). A history of cesarean section and pelvic lymphadenectomy was significant predictors.ConclusionsSurgical complications were common in this group. Cesarean section history and pelvic lymphadenectomy were linked to a higher risk. However, baseline QoL did not predict complications. Further research is needed to test this model in other patient groups.

Reirradiation for Recurrent Cervical Cancer Within the Previous Radiation Field Using a Bioabsorbable Spacer: A Case Report

ABSTRACT Reirradiation for cervical cancer recurrence in previously irradiated fields is challenging due to dose limitations. To our knowledge, this is the first case report describing successful reirradiation using a bioabsorbable spacer for vaginal cuff recurrence after initial concurrent chemoradiotherapy (CCRT) and hysterectomy. A 70‐year‐old woman with cervical cancer Stage IIIC2r initially received CCRT and chemotherapy. Three years later, uterine recurrence led to hysterectomy. Eighteen months post‐surgery, vaginal cuff recurrence was diagnosed by imaging and tumor biopsy. A bioabsorbable spacer was surgically placed around the vaginal cuff tumor via an open abdominal approach. Reirradiation (55 Gy in 22 fractions) was started 23 days postoperatively. Use of the spacer provided adequate dose reduction to the small bowel, sigmoid colon, and rectum, with the rectal D1cc reduced to 37.9 Gy. Mild paralytic ileus occurred, but resolved conservatively, and there were no severe complications. The patient remains disease‐free at 6 months post‐treatment. In this case, bioabsorbable spacer placement allowed safe reirradiation for cervical cancer vaginal cuff recurrence. This technique may represent a promising approach for selected patients with in‐field recurrent cervical cancer, although further accumulation of cases and longer follow‐up are required.

Application of Manual Lymph Drainage Combined With Complex Decongestive Therapy in Lower Limb Lymphedema After Cervical Cancer Surgery and Its Impact on Quality of Life

ABSTRACT Objective This paper aims to evaluate the effectiveness of manual lymph drainage (MLD) and complex decongestive therapy (CDT) in managing lower limb lymphedema (LLL) following cervical cancer surgery and its impact on patient quality of life. Methods Patients with postoperative LLL following cervical cancer surgery were included. A total of 57 patients in the control group received pneumatic compression therapy, while 57 patients in the CDT group received additional CDT. Outcomes included symptom relief rates, maximum limb circumference, tissue water content, and Gynecologic Cancer Lymphedema Questionnaire (GCLQ), Visual Analog Scale (VAS), and EORTC QLQ‐C30 score. Results Posttreatment, the CDT group had a higher total remission rate, smaller affected limb circumference, less extracellular and truncated water, lower GCLQ, VAS, and QLQ‐C30 symptom scores, and higher 50 kHz bioelectrical impedance and QLQ‐C30 health/function scores than the control group ( p  < 0.05). Conclusion CDT combined with pneumatic compression therapy was effective in treating LLL after cervical cancer surgery, reducing edema and pain in the lower limbs, and improving patients' quality of life.

HE4 is associated with clinical risk prognostic factors and survival outcome in primary fallopian tube carcinoma patients

AbstractAimTo explore whether HE4 was associated with clinical risk prognostic factors and survival outcome in primary fallopian tube carcinoma patients.MethodsNinety‐six primary fallopian tube carcinoma (PFTC) patients from March 2011 to June 2019 were enrolled in this study. Serum CA125 and HE4 concentrations were measured at four time points including primary diagnosis, postsurgery, pre‐recurrence, and recurrence. The relations between clinical risk prognostic factors with HE4 concentrations were investigated, and multivariate survival analysis was used to calculate the hazard ratios between HE4 levels with recurrence‐free survival and overall survival.ResultsHE4 were significantly elevated in poor performance status, advanced stage, high histological grade and residual tumor diameter >1 cm, and positive lymph node status, respectively, compared with those in well performance status, early stage, low histological grade, residual tumor diameter ≤1 cm, and negative lymph node status, respectively. Multivariate survival analysis indicated serum HE4 can predict outcome of recurrence‐free survival and overall survival with hazard ratios of 9.92 (95% confidence interval [CI]: 2.95–33.32) and 3.12 (95% CI: 1.07–9.08), respectively.ConclusionHE4 is associated with clinical risk prognostic factors in PFTC and contributes to predict survival outcome in PFTC cases.

Therapeutic impact of neoadjuvant chemotherapy on lymph node metastasis in locally advanced cervical cancer

Abstract Background Cervical cancer remains a global health concern. Lymph node (LN) metastasis, especially para‐aortic LN (PAN) involvement, is a critical prognostic factor. While neoadjuvant chemotherapy (NAC) followed by radical hysterectomy (RH) is used for locally advanced cervical cancer, its therapeutic effect on LN metastases remains uncertain. Method This retrospective study analyzed 110 patients treated with NAC followed by RH. Patients were grouped into nine cIIIC2 cases with PAN metastasis, 81 non‐cIIIC2 squamous cell carcinoma (SCC) cases, and 20 non‐squamous cell carcinoma (non‐SCC) cases. Non‐cIIIC2 SCC cases were further divided into four subgroups by LN status: cN1ypN1 ( n  = 16), cN1ypN0 ( n  = 24), cN0ypN1 ( n  = 10), and cN0ypN0 ( n  = 31). Tumor and LN size changes by NAC and survival outcomes were analyzed. Results In cIIIC2 cases, ypPAN‐negative patients showed significantly better 5‐year progression‐free survival (PFS) compared to ypPAN‐positive cases (100% vs. 0%, p  < 0.0001). Among non‐SCC cases, ypN1 patients ( n  = 9) had poorer outcomes than ypN0 cases ( n  = 11) (5‐year PFS: 25% vs. 90%, p  = 0.0005). As for non‐cIIIC2 SCC cases, tumor shrinkage rates varied among SCC subgroups: cN0ypN0 (−58.3%), cN1ypN0 (−45.5%), cN1ypN1 (−36.4%), and cN0ypN1 (−29.6%). cN0ypN1 cases also showed distinct recurrence patterns, with 66.7% experiencing distant metastases; however, prognosis did not differ among four LN‐related groups. Conclusion NAC can significantly improve prognosis in selected cases where LN metastases are eliminated, particularly in PAN and non‐SCC pelvic region metastasis cases. However, such cases are rare, emphasizing the need for better candidate selection and enhanced treatment strategies.

Impact of Power Morcellation and Histopathological Subtypes on the Development of Peritoneal Leiomyomatosis Following Laparoscopic Myomectomy

ABSTRACT Aim Laparoscopic myomectomy with power morcellation is a common approach for the management of uterine myomas. However, besides myoma recurrence, rare complications such as peritoneal leiomyomatosis may arise postoperatively. The histopathological subtype of fibroids—particularly cellular leiomyoma—may impact the risk of recurrence and dissemination, though current evidence remains limited. The aim of this study is to evaluate the impact of power morcellation on the development of disseminated peritoneal leiomyomatosis and to assess the association between the histopathological subtype of myoma and patient outcomes during follow‐up. Methods This retrospective cohort study analyzed 997 patients who underwent laparoscopic myomectomy with power morcellation at a single tertiary center between 2012 and 2024. Patients were followed through clinical evaluations and ultrasonography. Peritoneal leiomyomatosis was evaluated in relation to surgical technique (confined vs. unconfined morcellation) and histopathological subtype. Results Of the 553 patients with available follow‐up, myoma recurrence was observed in 130 (23.5%), reoperation in 53 (9.6%), and peritoneal leiomyomatosis in 8 patients (1.4%). All peritoneal leiomyomatosis cases occurred in the unconfined morcellation group. Cellular leiomyoma was identified in 5 of the 8 peritoneal leiomyomatosis cases (62.5%). One peritoneal leiomyomatosis case was diagnosed as leiomyosarcoma after surgery for disseminated leiomyomatosis. Overall myoma recurrence was significantly higher in patients with multiple myomas and in those with cellular leiomyoma. Conclusion Peritoneal leiomyomatosis is a rare complication of laparoscopic myomectomy and increased incidence after unconfined morcellation is a serious concern. Confined (in‐bag) morcellation appears to reduce the risk of peritoneal leiomyomatosis and should be the standard of care. Diagnosis of myomas as cellular leiomyoma subtype on histopathology merits high clinical suspicion for possibility of subsequent peritoneal leiomyomatosis in patients with unconfined morcellation. Therefore, close and long‐term follow‐up of these patients is essential.

Efficacy of Sentinel Lymph Node Sampling for Early Cervical Cancer: A Single Institute Study

ABSTRACT Aim Radioisotope (RI) tracers were approved for use in gynecological cancers in Japan in 2023, and their application in sentinel lymph node (SLN) biopsy for cervical cancer is expected to expand. Our institution has been performing SLN biopsies for cervical cancer since 2009. This study aimed to evaluate the efficacy and safety of SLN biopsy in patients with early‐stage cervical cancer. Methods This study included 136 patients with FIGO 2008 stage IA1 to IB1 cervical cancer who underwent hysterectomy with SLN mapping between January 2009 and December 2023. The SLNs were identified using a combination of RI and dye (patent blue) methods. Systematic pelvic lymph node dissection (PLND) was performed during the initial introduction period. Patients were divided into two groups: the PLND group ( n  = 50), who underwent systematic dissection until August 2012, and the sentinel node navigation surgery (SNNS) group ( n  = 86), who underwent SLN biopsy with systematic dissection only when SLN metastasis was detected. Recurrence, prognosis, and complications were compared between the groups. Results In the PLND group, the SLN detection rate was 84%, and the sensitivity for detecting lymph node metastasis was 100%. Lymphedema occurred in 5.8% and 20.0% of patients in the SNNS and PLND groups, respectively. The 5‐year progression‐free survival rates in the SNNS and PLND groups were 88.6% and 92.2% respectively. The 5‐year overall survival rates were 95.5% and 97.8%, respectively, with no significant differences observed. Conclusion SLN biopsy can improve the quality of life without compromising oncologic outcomes in early‐stage cervical cancer.

Effect of hemoglobin, albumin, lymphocyte, and platelet score on prognosis in intermediate‐risk endometrial cancer according to molecular‐based classification

AbstractObjectiveThe aim of this study is to compare the relationship between molecular classification and HALP score in endometrial cancer (EC).MethodsPatients who were operated with the diagnosis of EC 2014 and 2024 were included in our study. 150 patients were included in the study. We divided the patients into three groups in terms of molecular classification; group 1 was the patients with POLE mutation, group 2 was the patients with MMRd and NSMP (intermediate prognosis), and group 3 was the patients with p53 mutation. Group 2 participants were divided into two groups, a low HALP score group and a high HALP score group, according to the HALP score cut‐off value.ResultsUsing the value with the highest Youden's index (0.306) as a basis, it was demonstrated that the HALP score with a cut‐off value of 33.735 has a sensitivity of 61.86% and a specificity of 68.75% in intermediate‐risk EC. The 5‐year overall survival (OS) was found to be 75.4% in intermediate‐risk EC patients with low HALP scores and 91.5% in intermediate‐risk EC patients with high HALP scores (p = 0.008). The 5‐year progression‐free survival (PFS) was found to be 86% in intermediate‐risk EC patients with low HALP scores and 94.4% in intermediate‐risk EC patients with high HALP scores (p = 0.089). MMR deficiency and NSMP have been considered intermediate‐risk groups for endometrial cancer and are a heterogeneous group. Although the use of the HALP score to reduce this heterogeneity is successful in predicting OS, it is not sufficient for PFS.

Painless ruptured pyomyoma causing an abdominal abscess in a postmenopausal woman with abdominal hypoesthesia

Abstract Pyomyoma is a rare condition caused by an infection within a uterine leiomyoma. When ruptured, it can cause peritonitis with continuous abdominal pain, potentially leading to life‐threatening conditions. However, abdominal pain may be absent in patients with abdominal hypoesthesia. We report a case of painless ruptured pyomyoma causing an abdominal abscess in a 60‐year‐old woman with abdominal hypoesthesia. The patient with a T4‐level sensory deficit due to an acute disseminated encephalomyelitis sequela presented with persistent fever but no abdominal pain. She was initially diagnosed with appendicitis and received antibiotics; however, the inflammatory response and fever persisted. Further investigations revealed a ruptured pyomyoma forming an intra‐abdominal abscess. Additional antibiotic administration and extensive surgeries, including hysterectomy, bilateral salpingo‐oophorectomy, and ileocecal excision, resolved the severe peritonitis. The postoperative course was uneventful without any relapse. Lack of abdominal pain related to abdominal hypoesthesia can mask the severity of peritonitis.

Attitudes Towards Early Diagnosis of Cervical Cancer Among Women Applying to a Health Institution in Turkey

ABSTRACT Background Cervical cancer is one of the most common preventable gynecologic cancers, yet it remains a major public health problem worldwide. Objective This study was conducted to assess women's attitudes towards early detection of cervical cancer and to determine the factors affecting these attitudes. Methods A descriptive cross‐sectional study was conducted with 290 women admitted to a university hospital in Turkey between March and May 2025. Data were collected using a Personal Information Form and the Cervical Cancer Early Detection Attitude Scale Attitude Scale for Early Diagnosis of Cervical Cancer. Results The mean age of the participants was 40.86 ± 10.80 years. 84.1% of the women had heard of the Pap smear test, and 61.7% had this test. The mean total attitude score was 102.53 ± 10.46, indicating generally positive attitudes. Conclusion Women had positive attitudes towards early detection of cervical cancer. Improving access to counseling and screening services is necessary to reduce the burden of cervical cancer.

Obstetric Outcome After Trachelectomy for Cervical Cancer Without Uterine Artery Preservation

ABSTRACT Aim A trachelectomy is a fertility‐preserving surgery that is performed for cervical cancer. Transecting the uterine arteries (UAs) during abdominal radical trachelectomy (ART) or abdominal modified radical trachelectomy (AmRT) has the advantage of simplifying other surgical procedures. However, the effect of UA transection on subsequent pregnancy outcome is unknown. The purpose of this study was to clarify the pregnancy outcomes in post‐RT pregnancies in which the UAs were not preserved. Methods This was a retrospective cohort study of electronic case records involving pregnant women after ART and AmRT, which were managed at Kyushu University Hospital from January 2008 to July 2024. Results Complications that often occur in pregnancies after ART and AmRT, such as antepartum bleeding, premature birth, and preterm premature rupture of membranes, were noted to the same degree after UA‐sparing ART. In contrast, abnormalities related to placental attachment, such as placenta previa and adherent placenta, occurred at a high rate after UA transection. Furthermore, compared to pregnancies with normal placentation, pregnancies with abnormal placentation had more blood loss during cesarean section (1150 g vs. 2289 g; p  = 0.0004) and required blood transfusion more frequently (5.7% vs. 64.2%; p  < 0.0001). Conclusions Although ART and AmRT with UA transection may increase the risk of abnormal placentation and bleeding‐related complications during cesarean section, UA transection may not increase the risk of major obstetric complications after ART and AmRT. Therefore, UA transection should be considered during ART and AmRT due technical advantages.

Predictive value of abnormal expression of MPHOSPH9 in reintervention after high intensity focused ultrasound treatment of uterine fibroids

AbstractAimsAberrantly expressed MPHOSPH9 has been reported to be associated with poor prognosis in many diseases. Previous study indicates that MPHOSPH9 is abnormally expressed in patients with uterine fibroids (UFs). This study focused on the possible prognostic value of MPHOSPH9 in UFs patients after high intensity focused ultrasound (HIFU) treatment.MethodsA total of 455 UFs patients participated in the study, including 95 patients who needed reintervention (Reintervention group) and 360 patients who did not need reintervention (Non‐reintervention group) after HIFU treatment. They volunteered blood samples before HIFU treatment. The relative expression of MPHOSPH9 was assessed by qRT‐PCR. Cox regression analysis was performed to assess the prognostic value of MPHOSPH9 and risk factors of postoperative reintervention.ResultsThe expression of MPHOSPH9 was markedly elevated in Reintervention, compared to that of the Non‐reintervention group (p < 0.001). Five‐year follow‐up results showed that among these postoperative patients, 95 patients required reintervention and the reintervention time mainly occurred during 10–40 months after surgery. The Cox regression analysis demonstrated that UFs size (hazard ratio = 2.769, 95% confidence interval: 1.366–5.610) and the high MPHOSPH9 expression level (hazard ratio = 3.160, 95% confidence interval: 1.506–6.630) were independent risk factors for postoperative reintervention.ConclusionsThe enhanced MPHOSPH9 was a potential candidate for predicting postoperative reintervention in UFs patients.

Fertility Preservation in Extramedullary Plasmacytoma of the Uterine Cervix: Global Literature Synthesis and First Case From Iran

ABSTRACT Aim Extramedullary plasmacytoma ( EMP ) most commonly arises in the head and neck, with exceedingly rare involvement of the uterine cervix. Only 16 published cases of cervical EMP have been reported since 1949. This study presents the first documented case from Iran and synthesizes all reported cases to analyze clinical patterns, diagnostic pitfalls, and management strategies. Methods A 32‐year‐old Iranian woman presented with postcoital bleeding after years of intermittent spotting. Comprehensive workup in March 2024, excluded multiple myeloma. Due to her desire for pregnancy, she declined hysterectomy and radiotherapy and underwent cervical conization in June 2024, with concurrent endocervical and endometrial sampling. We also conducted a systematic review of all published cervical EMP cases. Results Our analysis of 16 published cervical EMP cases (including present case) demonstrates that clinical presentations are nonspecific, commonly postcoital bleeding or abnormal Pap smears, often leading to initial misdiagnosis. Treatment was highly individualized: 9 patients underwent surgery, 6 received radiotherapy (± surgery), and outcomes were generally favorable. Notably, fertility‐sparing conization alone was associated with disease‐free survival in three young patients, including ours, supporting the feasibility of fertility‐sparing strategies under strict surveillance. Conclusions This case contributes critical evidence that organ‐sparing management can be oncologically appropriate. Cervical EMP should be considered in differential diagnosis of atypical cervical lesions. In the absence of standardized guidelines, management must be tailored to patient values and anatomical context, not based on general EMP guidelines. Continued reporting of well‐documented cases is critical to refine prognostic and therapeutic insights for this ultra‐rare entity.

Cellular leiomyoma: A 10‐year retrospective analysis of clinical features, and recurrence risk

Abstract Objectives In this study, we aimed to compare the clinical characteristics of cellular leiomyoma (CL) with those of typical uterine leiomyoma (UL) and explore recurrence risk factors in patients with CL myomectomy. Study Design In this retrospective cohort study, we analyzed medical records of patients diagnosed with CL ( n  = 102) and UL ( n  = 105) who underwent surgery between January 2013 and May 2023. Postoperative prognosis was assessed through patient follow‐up until June 2024. Results Patients with CL were likelier to have adenomyosis (odds ratio [OR], 4.06; 95% confidence interval [CI], 1.28–12.88; p  = 0.017) and late‐age menarche (OR, 1.50; 95% CI, 1.15–1.95; p  = 0.002). A uterus that has three or fewer fibroids (OR, 2.14; 95% CI, 1.05–4.37; p  = 0.037) was more likely to develop into CL than the control group. Concerning the predictive aspect, more than three fibroids are associated with a higher risk of recurrence (OR, 5.33; 95% CI, 1.02–27.76; p  = 0.047). The use of hysteroscopy to remove submucosal fibroids is associated with a lower risk (OR, 0.08; 95% CI, 0.01–0.78; p  = 0.030). Conclusions This study confirms that CL exhibits distinct clinical characteristics from ULs, with a higher postoperative recurrence rate and risks of malignant transformation and abdominal dissemination. Our study identified for the first time that adenomyosis is an independent risk factor for CL. Additionally, submucous fibroids tend to be resected while still small, allowing for more complete removal and reducing recurrence risk. An increased number of fibroids was also identified as a risk factor for recurrence.

Fertility‐Sparing Trachelectomy With Sentinel Node Mapping in Early‐Stage Cervical Cancer: Oncological Safety and Obstetric Outcomes From a Single‐Institution Study

ABSTRACT Aim Trachelectomy is a fertility‐preserving surgical approach for early‐stage cervical cancer. To enhance oncological safety, intraoperative sentinel lymph node (SN) evaluation has been incorporated. This study aimed to evaluate the long‐term oncological and obstetric outcomes of trachelectomy with SN biopsy. Methods We enrolled 53 patients who underwent trachelectomy with intraoperative SN assessment at Kagoshima University Hospital between 2014 and 2022. The preoperative and intraoperative eligibility criteria were strictly applied. Surgical and obstetric outcomes were evaluated, and recurrence‐free survival (RFS) and overall survival (OS) were calculated using the Kaplan–Meier analysis. Results Among the 78 candidates, 53 met all criteria and successfully underwent trachelectomy. The 5‐year RFS and OS rates were both 98%. Bilateral SNs were detected in 98% of patients, and intraoperative SN biopsy‐guided surgical decisions were made. Postoperative complications occurred in 6% of the patients. Of the 19 patients who attempted conception, 10 (53%) became pregnant, leading to 8 live births (five preterm, three term). In vitro fertilization and embryo transfer were used in 60% of the pregnancies. Pregnancy was associated with a high risk of preterm delivery. Conclusions Trachelectomy with intraoperative SN biopsy is a feasible and safe treatment option for appropriately selected patients with early‐stage cervical cancer. It offers excellent oncological outcomes and acceptable fertility potential. However, the risk of obstetric complications, particularly preterm births, remains high. Structured postoperative and perinatal management is crucial. Further prospective multicenter studies are warranted to validate and refine this approach.

The association between age and re‐intervention rates in uterine fibroid patients after UsgHIFU therapy: A cohort study

Abstract Aim To investigate the correlation between patient age and long‐term re‐intervention requirements for symptomatic uterine fibroids through stratified age‐group analysis following ultrasound‐guided high‐intensity focused ultrasound (UsgHIFU) ablation therapy. Methods This retrospective cohort study evaluated 443 uterine fibroids from the Liuzhou Maternal and Child Healthcare Hospital (2018–2020). Post‐ablation re‐intervention trajectories were monitored over 36 months following UsgHIFU. Age‐stratified analyses included analysis of variance for continuous parameters and χ 2 tests for categorical variables. Nonlinear dynamics were modeled using multivariable adaptive regression splines, with threshold regression identifying clinically significant transition points. Results Among the 443 patients who underwent UsgHIFU, 35 (7.9%) required re‐intervention within 36 postoperative months. Adjusted odds ratio (OR) analysis revealed distinct age‐dependent patterns. For patients below the 39‐year threshold, each additional year demonstrated a positive association with re‐intervention risk (OR = 1.20, 95% confidence interval [CI] 1.05–1.37; p  = 0.0079). Conversely, in patients aged ≥39 years, each additional year showed a statistically significant negative association with re‐intervention (OR = 0.70, 95% CI 0.56–0.87; p  = 0.0012). Conclusions In patients with uterine fibroids undergoing UsgHIFU, the correlation between age and the risk of re‐intervention after treatment follows an inverted U‐shaped curve. Both older and younger age groups are associated with a reduced risk of re‐intervention. UsgHIFU is a noninvasive and effective method for treating uterine fibroids. Patients who undergo UsgHIFU treatment experience a low re‐intervention rate, with younger patients or those closer to menopause achieving better treatment outcomes.

Laparoscopic management of symptomatic uterine myoma in pregnancy: A case report and critical analysis of literature

Abstract Abdominal pain during pregnancy poses diagnostic and management challenges. Uterine leiomyomas complicate 2 to 10% of pregnancies, with severe pain in some cases necessitating surgical intervention. While myomectomy during pregnancy is generally avoided due to increased vascularity and risk of hemorrhagic complications, specific indications warrant consideration, such as severe pain from torsion, hemoperitoneum, or red degeneration. We describe a case of acute abdominal pain at 19 weeks of pregnancy caused by acute uterine myoma degeneration, detailing the diagnostic process, differential diagnosis, and treatment. Our case, along with a discussion of the scarce available literature, highlights that laparoscopic myomectomy during pregnancy is a feasible option for managing symptomatic fibroids. Timely diagnosis, centralized care, and tailored surgical planning are critical to optimizing maternal and fetal outcomes.

A case of uterine liposarcoma with PLAG1 rearrangement that was difficult to classify into established subtypes

Abstract Herein, we present a case of International Federation of Gynecology and Obstetrics stage IIIB (pT3bNxM0) uterine liposarcoma. Although intensive tumor resection was performed, the patient died 53 days after surgery. The resected surface of the tumor showed a yellowish hemorrhagic infarction. Histologically, adipocytes and lipoblasts were observed in the myxoid stroma. Immunohistochemical examination revealed that the tumor was diffusely positive for PLAG1 (pleomorphic adenoma gene 1) and focally positive for S100 protein and CDK10. The tumor was negative for smooth muscle actin, desmin, MDM2, CDK4, ER, ALK, STAT6, NKX2.2, SS18, DDIT3, BCOR, and pan‐TRK. Fluorescence in situ hybridization showed that the tumor had a PLAG1 gene rearrangement. However, further examination using RNA sequencing analysis failed to identify specific sequences. As the tumor was difficult to classify into the four subtypes of liposarcoma, the current disease might be a new type of uterine liposarcoma.

Diagnostic and prognostic values of serum insulin‐like growth factor binding protein 4 expression in cervical cancer

Abstract Objective Insulin‐like growth factor binding protein 4 (IGFBP4) is lowly expressed in cervical cancer (CC) cells. However, it remains unclear about its expression and diagnostic and prognostic values in CC. Therefore, this research probed the serum expression of IGFBP4 in CC patients and its diagnostic and prognostic values. Methods This study prospectively included 146 CC patients admitted to our hospital (the CC group) from January 2018 to June 2020 and 146 patients with cervical intraepithelial neoplasia (CIN) admitted to the hospital (the CIN group) and 146 normal women receiving health checkups during the same period (the normal group). Serum IGFBP4 expression in CC patients was detected with quantitative reverse transcription‐polymerase chain reaction. Receiver‐operating characteristic (ROC) curves were utilized to evaluate whether serum IGFBP4 expression could assist in predicting CC occurrence. Kaplan–Meier survival analysis and Cox regression analysis were utilized to assess the significance of serum IGFBP4 expression in the prognosis of CC patients. Results IGFBP4 was downregulated in serum from CIN and CC patients, with lower expression in CC patients. Marked differences were noted in histologic differentiation, FIGO stage, and lymph node metastasis between the high and low IGFBP4 expression groups. The area under the ROC curve of serum IGFBP4 expression to assist in CC diagnosis was 0.9206 (cut‐off, 0.8450; sensitivity, 86.30%; specificity, 81.51%). Low serum expression of IGFBP4 augmented the risk of poor prognosis in CC patients and was an independent risk factor for poor prognosis. Conclusion Low serum expression of IGFBP4 can assist in CC diagnosis and is an independent risk factor for the dismal prognosis of CC patients.

Comparison of outcomes between laparoscopic and open radical hysterectomy for early‐stage cervical cancer in women with body mass index greater than 24

Abstract Aim This is a retrospective cohort study to compare outcomes of laparoscopic radical hysterectomy (LRH) and open radical hysterectomy (ORH) in overweight and obese women with early‐stage cervical cancer. Methods The study included 112 patients, with 50 undergoing LRH and 62 undergoing ORH; these were overweight or obese women (BMI ≥24 kg/m 2 ) diagnosed with stage IB–IB2 cervical cancer from 2015 to 2022 Baseline characteristics, including age, smoking status, alcohol consumption, BMI, number of pregnancies, history of abortion, previous abdominal surgeries, menopausal status, radiation therapy, neoadjuvant chemotherapy, clinical tumor stage, tumor grade, or histological subtype, were comparable between the ORH and LRH groups. Results LRH was associated with significantly lower intraoperative blood loss (165 mL vs. 604 mL, p  < 0.001) and shorter hospital stays (9 vs. 11.5 days, p  < 0.001). No significant differences were observed in overall survival and disease‐free survival of 1‐year, 3‐year, and total between the two groups. Complication rates were similar; though, LRH resulted in significantly fewer incidences of wound fat liquefaction. Conclusion Despite the technical challenges associated with LRH in obese patients, the procedure demonstrated clear benefits in terms of reduced blood loss and quicker postoperative recovery. The oncological safety of LRH was comparable to ORH, supporting its use as a viable and potentially preferable option for surgical management of early‐stage cervical cancer in overweight and obese women.

Vaginal metabolic profiling reveals biomarkers characteristics of high‐risk HPV infection and cervical lesions

Abstract Objective This study aimed to identify potential biomarkers in high‐risk human papillomavirus (HR‐HPV) infections and related cervical lesions through the analysis of vaginal metabolic profiles. Patients and methods Forty cervicovaginal secretion samples were collected from healthy individuals, HR‐HPV‐positive individuals, low‐grade squamous intraepithelial lesion patients, high‐grade squamous intraepithelial lesion patients, and cervical cancer (CC) patients. All samples were analyzed using liquid chromatography–mass spectrometry (LC–MS). Metabolites with significant differences were identified using the variable importance in projection (VIP > 1) derived from the orthogonal least partial squares discriminant analysis (OPLS‐DA) model and the p ‐value ( p  < 0.05) of the Student's t test. Utilizing hierarchical cluster analysis and receiver operating characteristic curve analysis, the optimal biomarkers were identified, and the diagnostic potential of these biomarkers was evaluated. Significantly enriched pathways of the differential metabolites were explored using metabolic pathway analysis. Results LC–MS analysis of the vaginal metabolomic profiles revealed unique molecular characteristics of different states of HR‐HPV infection. Based on persistent HR‐HPV infection, 3‐Isochromanone increased, and DG(2:0/5‐iso PGF2VI/0:0) and (4R,5S,7R,11x)‐11,12‐Dihydroxy‐1(10)‐spirovetiven‐2‐one 12‐glucoside decreased ( p  < 0.05) with the aggravation of cervical lesions, suggesting their potential as biomarkers to predict various stages of cervical lesions. Additionally, analysis of metabolic pathway enrichment for differential metabolites identified the phenylalanine, tyrosine, and tryptophan biosynthesis pathways as the key metabolic pathways in the progression of cervical lesions. Conclusion By measuring the metabolome of vaginal secretions, specific metabolites can effectively distinguish persistent HR‐HPV infections and different grades of cervical lesions, which may become an important means for the early screening and diagnosis of CC.

Concurrent cisplatin chemotherapy with intensity‐modulated radiotherapy followed by consolidation chemotherapy in early‐stage cervical cancer patients with high‐risk factors after radical hysterectomy

AbstractObjectivesTo evaluate the efficacy and toxicity of consolidation chemotherapy (C‐CT) following concurrent cisplatin chemotherapy combined with intensity‐modulated radiotherapy (IMRT) in patients with early‐stage cervical cancer who present high‐risk factors (HRFs).MethodsBetween 2013 and 2023, a total of 190 women were included in this retrospective study. Among these, 82 patients received postoperative concurrent chemoradiotherapy (CCRT) with weekly cisplatin and IMRT (45.0–50.4 Gy), followed by C‐CT, while 108 patients received CCRT alone. A propensity score matching (PSM) was performed with a ratio of 1:1. Clinical parameters, overall survival (OS), and relapse‐free survival (RFS) were analyzed for both groups.ResultsThe median follow‐up duration was 50.2 months. The 4‐year OS rates were 88.7% in the C‐CT group and 87.9% in the CCRT‐only group (p = 0.886). The 4‐year RFS rates were 76.3% for the C‐CT group and 80.5% for the CCRT‐only group (p = 0.289). In patients with three or more positive lymph nodes, C‐CT was associated with significantly improved OS compared to the CCRT‐only group (HR 0.14, 95% CI 0.02–0.88, p = 0.036), while RFS showed no significant difference (HR 0.80, 95% CI 0.27–2.32, p = 0.676). However, the incidence of grade 3/4 hematologic toxicity was higher in the C‐CT group (16.8% vs. 1.7%, p = 0.009).ConclusionsOur study found that C‐CT following concurrent cisplatin chemotherapy with IMRT did not confer additional benefits over CCRT alone in the majority of early‐stage cervical cancer patients with HRFs, except in those with three or more positive lymph nodes.

Comparison of the risk of ovarian malignancy algorithm and Copenhagen Index for the preoperative assessment of Japanese women with ovarian tumors

AbstractObjectiveTo compare the risk of ovarian malignancy algorithm (ROMA) and Copenhagen Index (CPH‐I) in their ability to distinguish epithelial ovarian cancer (EOC) and malignant ovarian tumors (MLOT) from benign ovarian tumors (BeOT) in Japanese women.MethodsPatients with pathologically diagnosed ovarian tumors were included in this study. The study validated the diagnostic performance of ROMA and CPH‐I.ResultsAmong the 463 Japanese women included in this study, 312 had BeOT, 99 had EOC, and 52 had other MLOT. The receiver‐operator characteristic (ROC) area under the curve (AUCs) of ROMA (0.89) and CPH‐I (0.89) for distinguishing EOC from BeOT were significantly higher than that of CA125 (0.82) (CA 125 vs. ROMA; p = 0.002, vs. CPH‐I; p < 0.001). The ROC‐AUCs of ROMA (0.82) and CPH‐I (0.81) for distinguishing MLOT from BeOT were significantly higher than that of CA125 (0.75) (CA 125 vs. ROMA: p = 0.003, vs. CPH‐I: p < 0.001). The sensitivity (SN)/specificity (SP) of ROMA and CPH‐I for distinguishing EOC from BeOT at standard cut‐off points were 69%/90%, and 69%/90%, respectively, those for distinguishing MLOT from BeOT were 54%/90%, and 55%/90%, respectively.ConclusionROMA and CPH‐I performed comparably well and better than CA125 in distinguishing EOC from BeOT in Japanese women. ROMA and CHP‐I should be used with caution in practical situations, where all histological possibilities for must be considered, because the SNs of ROMA and CPH‐I were only 54% and 55%.

Concurrent chemoradiotherapy for advanced cervical cancer during second trimester pregnancy: A case report

AbstractIn Japan, pregnancies complicated by cervical cancer are rising due to the higher incidence of cervical cancer among younger women, coupled with an increase in maternal age. Evidence regarding the treatment of cervical cancer during pregnancy is limited, especially for advanced cases that cannot be managed surgically. We present a case of stage IIIC1r cervical cancer in a 30‐year‐old woman, in which concurrent chemoradiotherapy (CCRT) was initiated at 15 weeks of gestation, with the fetus remaining in utero. Intrauterine fetal death was confirmed on the 21st day of treatment, and the fetus was delivered at 38 days. The patient completed CCRT with minimal delay and achieved complete tumor remission, with no recurrence observed at 1 year. This case also highlights the importance of early multidisciplinary intervention.

Comparison of oncological outcomes between radical hysterectomy and radiochemotherapy for International Federation of Gynecology and Obstetrics 2018 stage IIIC1 cervical adenocarcinoma: A retrospective multicenter cohort study

AbstractBackgroundTo compare oncological outcomes of radical hysterectomy (RH) and radiochemotherapy (R‐CT) for stage IIIC1 (FIGO 2018) cervical adenocarcinoma patients.MethodsBased on the Chinese Cervical Cancer Clinical Diagnosis and Treatment Project Database, we retrospectively reviewed 236 cases of FIGO stage IIIC1 cervical adenocarcinoma diagnosed between 2005 and 2019. The 5‐year overall survival (OS) and 5‐year disease‐free survival (DFS) rates were compared between the two treatment groups using multivariate Cox regression models and the log‐rank test, both in the overall study population and after propensity score matching (PSM).ResultsFrom 63 926 patients, we selected 236 cases, including 203 in the RH group and 33 in the R‐CT group. In the overall study population, R‐CT was associated with significantly worse 5‐year OS (51.8% vs. 67.2%, p < 0.05) and 5‐year DFS (43.1% vs. 60.1%, p < 0.05) compared to RH. Multivariate analysis revealed that R‐CT was an independent risk factor for 5‐year DFS (hazard ratio [HR] = 2.226, 95% confidence interval [CI] 1.141–4.343, p < 0.05) but not for 5‐year OS (HR = 1.834, 95% CI: 0.829–4.061, p > 0.05) in FIGO stage IIIC1 cervical adenocarcinoma. After matching (n = 26 in R‐CT group vs. 73 in RH group), the R‐CT group showed significantly lower 5‐year OS (50.3% vs. 77.4%, p < 0.05) and DFS (38.2% vs. 65.0%, p < 0.05) compared to the RH group. In the matched cohort, R‐CT remained an independent risk factor for 5‐year DFS (HR = 2.299, 95% CI: 1.113–4.750, p < 0.05) but not for 5‐year OS (HR = 1.926, 95% CI: 0.792–4.682, p > 0.05).ConclusionAmong patients with stage FIGO 2018 IIIC1 cervical cancer adenocarcinoma, R‐CT was not associated with better oncological outcomes than RH. Radiotherapy should not be the only recommended treatment.

Fertility‐sparing management of stage IIIC serous borderline ovarian tumor: A case report of a 20‐year follow‐up

AbstractMultimodal treatment, including assisted reproductive technology, is necessary in young patients with advanced borderline ovarian tumors. However, the details of long‐term follow‐up cases have not been reported. In this report, a 19‐year‐old patient presented with a stage IIIC serous borderline tumor. The patient underwent five fertility‐sparing surgeries. The tumor did not respond to any of the three lines of chemotherapy administered. Serological and radiological responses were observed following hormonal treatment with leuprorelin, followed by a fourth surgery. Before the planned fifth surgery for complete resection of both adnexa, cryopreservation of the fertilized eggs was performed. At age 36, when the disease‐free interval exceeded the previous one, we proposed embryo transfer; however, she declined fertility treatment. The patient had developed rheumatoid arthritis and childbirth not a priority. The patient had lived without any evidence of disease for 7 years following the last surgery and 20 years after the initial visit.

The persistence of HPV type‐specific infections in patients following colposcopic examination: An observational study

AbstractAimHigh‐risk HPV infection is a necessary but not sufficient factor for the development of precancerous lesions and cervical cancer. Beyond mere HPV positivity, the persistence of infection over time plays a crucial role. This study aims to evaluate the clearance and persistence rates of HPV 16 and 18 genotypes.MethodsThe cervical cytology results were reported using the 2014 Bethesda System classification. The cervical cytology samples were analyzed using the Roche Cobas® 4800 HPV tests. Patients with any HPV genotype other than 16 or 18, those with missing data, those who were lost to follow‐up, those who underwent excisional procedures or hysterectomy, and those with high‐grade cervical dysplasia were excluded from this study.ResultsAmong 191 patients (mean age: 41.2 ± 0.6 years, 16.8% postmenopausal), the mean follow‐up was 21.6 ± 0.7 months. No significant differences were found between the clearance and persistence groups in age, follow‐up duration, cervical biopsy, or endocervical curettage results. However, HPV 16 had a higher persistence rate (28.2%), and abnormal cytology was more frequent in the persistence group (p = 0.038).ConclusionsAround 25% of patients had persistent HPV infection. Close monitoring is essential for those with CIN 1 on initial colposcopy, as they may have a higher risk of progressing to high‐grade dysplasia compared to those without dysplasia.

Long‐term impact of lymphadenectomies in patients with low‐grade, early‐stage uterine endometrial stroma sarcoma

AbstractAimThe aim of our study was to investigate the lymph node metastasis (LNM) rate and effect of lymph node dissection (LND) in patients with stage I, low‐grade endometrial stromal sarcoma (LGESS).MethodsPatients with stage I LGESS (n = 119) that underwent surgery from July 1969 to July 2017, following up over 48 years at the China National Cancer Center were retrospectively analyzed in this study.ResultsSurgical records and consulting data for patients with LGESS were analyzed to find that 47 patients received systematic pelvic LND. The number of patients with menopause in the LND(+) group were significantly lower than those in LND(−) group (2.1% vs 22.2%, P = 0.005), meanwhile, patients received bilateral salpingo‐oophorectomy procedure in LND(+) group were significantly higher than LND(−) (97.9% vs 58.3%, P < 0.001). Neither progression‐free survival nor overall survival was significantly improved in the LND(+) group even after propensity score matching although the progression‐free survival has a stronger trend in LND(+) population.ConclusionA systematic LND was not significantly associated with prognosis for patients with early‐stage LGESS. There is no sufficient indication for a systematic LND for patients with early‐stage LGESS. A systematic LND might be necessary if enlarged lymph nodes were detected by image graphology or observation during surgery.

Challenges in managing atypical glandular cells in cervical smears: Insights from real‐world data and clinicians' perspectives

AbstractObjectiveThis study evaluates clinicopathological outcomes and clinicians' awareness regarding the management of atypical glandular cells (AGC).MethodsWe analyzed 98 AGC cases, excluding known endometrial cancer, from 238 initial cases, with a median age of 42 years (range 20–82). Cytological findings, including NOS and FN subcategories, diagnostic tests, treatments, and outcomes were evaluated. A survey on AGC awareness and practices was conducted among 134 obstetrician‐gynecologists.ResultsOf 98 cases (AGC‐FN: 19.8%, AGC‐NOS: 13.2%, unspecified: 67.3%), 44.9% initially showed no neoplasia; this dropped to 38.8% following up, identifying 11 additional AIS or cervical adenocarcinomas. Overall, 28.5% had AIS or more, 18% had CIN, and 13.3% had other malignancies, indicating some over/underdiagnosis. HPV testing in 79 cases showed a 48.1% positivity rate, including 14 type‐18 and 12 type‐16 cases. Among clinicians surveyed, 25% were aware of AGC subcategories, and only 11.9% were well‐versed. Approximately 65% associated AGC with malignancy or precancerous lesions, and 52.6% used multiple diagnostic methods simultaneously. Even in the absence of neoplasia, 80% continued cytological examinations every 3–4 months.ConclusionThis study underscores the challenges in AGC management, highlighting the importance of follow‐up and collaboration between clinicians and cytopathologists to detect significant lesions. It also emphasizes the need for providing learning opportunities for clinicians to address over/undertreatment.

Epithelioid trophoblastic tumor diagnosed during a thorough examination of recurrent implantation failure: A case report

AbstractWe describe an exceptionally rare case of epithelioid trophoblastic tumor (ETT) in a patient with recurrent implantation failure (RIF). A 38‐year‐old Japanese woman, gravida 1, para 1, was diagnosed with RIF following three unsuccessful cryopreserved morphologically good embryo transfers with hormone replacement cycles after thawing. She underwent hysteroscopy and endometrial biopsy to exclude chronic endometritis but was referred because ETT was strongly suspected. Following a preoperative diagnosis of stage I ETT, she underwent laparoscopic total hysterectomy and bilateral salpingo‐oophorectomy. A yellowish elevated lesion was observed in the lower uterine body. Immunohistochemical staining was negative for human chorionic gonadotropin and human placental lactogen and positive for p63, with a Ki‐67 proliferation index of >10%. She was diagnosed with stage I ETT, but postoperative chemotherapy was not administered because of the lesion location and occurrence within 48 months of the prior term delivery. She had no recurrence at 24 months postoperatively.

Utility of manual vacuum aspiration followed by curettage in the treating hydatidiform mole: A retrospective analysis

AbstractAimWhile manual vacuum aspiration (MVA) is commonly employed for early first‐trimester abortions, its effectiveness in treating hydatidiform mole is still unclear. This study sought to evaluate the efficacy and safety of MVA in comparison to dilation and curettage (D&C) for managing hydatidiform mole.MethodsWe conducted a retrospective review of medical records for 198 patients with hydatidiform mole treated at Nagoya University Hospital between 2004 and 2023. After excluding cases with incomplete data, we compared 106 patients who underwent D&C with 60 patients treated with MVA followed by curettage. We evaluated the surgical duration, intraoperative blood loss, and the occurrence of post‐molar gestational trophoblastic neoplasia (GTN) in both groups.ResultsThe surgical duration and blood loss were similar between the MVA and D&C groups. The average surgical time was 13.2 min for D&C and 11.8 min for MVA (p = 0.145). Most cases in both groups experienced blood loss of less than 10 mL, with no significant difference (p = 0.066). Over a median follow‐up period of 33.4 months, 25 cases developed post‐molar GTN. All GTN cases originated from complete hydatidiform mole (25 of 132 cases, 18.9%), and none were from partial hydatidiform mole. Kaplan–Meier analysis, focusing only on patients with complete hydatidiform mole, indicated no significant difference in the time to onset of GTN between the D&C and MVA groups (p = 0.632).ConclusionsMVA followed by curettage is a viable approach for treating molar pregnancy.

Latest findings in chemotherapy

AbstractRadiotherapy and surgery are the two pivotal curative treatments for cervical cancer. Although cervical cancer is relatively sensitive to chemotherapy, chemotherapy is not included in the curative treatment of cervical cancer and has a role in limited medical conditions. Chemotherapy used to treat cervical cancer can be divided into four categories: (1) preceding chemotherapy (neoadjuvant chemotherapy) to augment the effects of radical therapy (surgery or radiation therapy), (2) chemotherapy administered concurrently with radiation therapy, and (3) adjuvant chemotherapy administered after radical therapy. In addition, (4) chemotherapy is used to prolong survival and alleviate symptoms in patients who cannot be radically cured. Recently, molecular targeted agents, angiogenesis inhibitors, and immune checkpoint inhibitors have been incorporated into existing chemotherapy regimens. This review summarizes these trends along with the history of chemotherapy for cervical cancer.

Asia Oceania Federation of Obstetrics and Gynecology (AOFOG)'s efforts in the cervical cancer elimination program in the Asia‐Pacific

AbstractCervical cancer poses a significant health burden, particularly in low‐ and middle‐income countries, where access to screening and treatment remains limited. Asia Oceania Federation of Obstetrics and Gynecology (AOFOG)'s response, guided by the World Health Organization's global strategy, emphasizes three key targets: achieving high HPV vaccination coverage among girls, ensuring widespread screening with high‐performance tests, and guaranteeing timely treatment for precancerous and cancerous lesions. AOFOG supports member countries through initiatives such as educational campaigns, guidelines development, and collaboration with local and international partners. Variations in screening methods across AOFOG member countries reflect diverse socioeconomic contexts and healthcare infrastructures, ranging from HPV testing in countries like Australia and Malaysia to cytology and visual inspection methods in others. Innovations such as HPV self‐testing and AI‐enhanced screening are emerging to improve accessibility and accuracy, addressing barriers like stigma and resource scarcity. Despite challenges, AOFOG remains committed to reducing cervical cancer incidence and mortality through coordinated regional efforts, aiming for equitable access to preventive measures and treatment across the diverse landscape of the Asia‐Pacific region.

A study on the efficacy and safety of long‐term adjusted low‐dose gonadotropin‐releasing hormone agonist therapy for uterine fibroids and adenomyosis

AbstractAimTo investigate the efficacy and safety of long‐term adjusted low‐dose gonadotropin‐releasing hormone agonist therapy (GnRH agonist drawback therapy) with nafarelin acetate in patients with uterine fibroids and/or adenomyosis with menstrual symptoms.MethodsThis single‐center, retrospective, observational study initially included 118 patients with uterine fibroids and/or adenomyosis with menstrual symptoms who had received GnRH agonist (nafarelin acetate) drawback therapy for at least 7 months between 2010 and 2020.Blood hemoglobin level, maximum fibroid diameter, area of the corpus uteri, blood estradiol level, daily dosage of nafarelin acetate, and bone density in the lumbar spine and femoral neck were assessed before and after the treatment initiation.ResultsThe median treatment period was 28 months. Menstruation had ceased in all patients. The median hemoglobin level significantly increased from 8.6 to 13.2 g/dL before treatment and at 12 months after the treatment initiation in patients with fibroids and from 8.8 to 13.3 g/dL in patients with adenomyosis, respectively. Although the treatment did not exert a significant shrinking effect on the fibroids and adenomyosis, an increase in their size was not observed in any patient. The initial dose of nafarelin acetate was 400 μg/day and was lowered to 130 μg/day at 12 months. Only 29 patients (25%) had an estradiol level <30 pg/mL. The average rate of bone density change over 6 months was −1.23% in the lumbar spine and −1.12% in the femoral neck in patients with fibroids and −1.06% in the lumbar spine and −0.14% in the femoral neck in patients with adenomyosis, which were lower than the previously reported rates.ConclusionsGnRH agonist drawback therapy was found to be useful for the long‐term conservative treatment of uterine fibroids and adenomyosis. The treatment was safely and inexpensively performed with few adverse events.

Safety and efficacy of tisotumab vedotin with cervical cancers: A systematic review and meta‐analysis

AbstractBackgroundTisotumab vedotin (TV) holds promise for treating recurrence or metastatic cervical cancer (r/mCC), with recent FDA approval for second‐line use in recurrent or metastatic cases. Our research aims to evaluate TV's efficacy and safety in these patients, focusing on overall survival (OS) and progression‐free survival (PFS) outcomes.MethodsWe searched five electronic databases in February 2024, retrieved articles, screened them based on inclusion and exclusion criteria, and assessed their quality. A meta‐analysis of the extracted data was performed and applied a random‐effects model for our analysis.ResultsThe search identified 86 articles, with six meeting the inclusion criteria. Meta‐analysis revealed 80.8% and 48.0% OS at 6 and 12 months, and a 29.9% PFS at 6 months. Combined treatment with carboplatin or pembrolizumab showed 33.0% PFS at 1 year and 15.1% at 2 years. The objective response rate (ORR) was 21.0%, reaching 43.3% with combined treatment. Confirmed disease control rate (CDCR) was 70.0% overall and in combination. The median duration of response (DOR) was 6.1 months, increasing to 9.5 months in combined treatment, with a consistent time to response (TTR) of 1.4 months. Adverse events included ocular issues (conjunctivitis 30.3%, dry eye 18.7%) and common side effects (nausea 38.4%, epistaxis 35.7%).ConclusionThis systematic review and meta‐analysis highlights the potential of TV as a treatment option for r/mCC patients. However, healthcare providers must communicate safety profiles and recommend prophylactic measures for optimal patient outcomes. Further studies, particularly assessing combination treatments, are needed to clarify TV's role in treatment algorithms and improve clinical outcomes.

Incidence and risk factors of parasitic myoma after laparoscopic myomectomy using uncontained power morcellation: Retrospective analysis of 87 patients who had a subsequent second laparoscopic surgery

AbstractAimStudies on parasitic myomas after laparoscopic morcellation are mainly limited to case reports, and the incidence and risk factors have not yet been well‐understood. We aimed to clarify the actual incidence and risk factors of parasitic myoma after laparoscopic myomectomy using uncontained power morcellation by reviewing cases with subsequent laparoscopic surgery.MethodsThis retrospective study included 87 patients who had laparoscopic myomectomy using uncontained power morcellation, followed by subsequent second laparoscopic surgery for gynecological disease between 2008 and 2021. First, the incidence and characteristics of parasitic myomas detected at the second laparoscopic surgery were reviewed. Second, patients were stratified according to the presence of parasitic myoma (PM+ and PM− groups), and risk factors were analyzed by comparing the background, intraoperative findings, and clinical course after laparoscopic myomectomy.ResultsOf the 87 patients, parasitic myomas were detected in 16 (18.4%). Twelve patients (75.0%) were asymptomatic and diagnosed incidentally during surgery. Two patients presented with acute abdomen requiring emergency surgery. Comparing the PM+ and PM− groups, the total weight of the enucleated myomas and the diameter of the largest myoma at the initial laparoscopic myomectomy were significantly greater in the PM+ group. Other factors, including age and number of enucleated myomas did not differ between the groups.ConclusionsThe actual incidence of parasitic myoma after laparoscopic myomectomy using uncontained power morcellation is higher than that previously reported. In laparoscopic power morcellation, large myomas increase the risk of developing parasitic myoma, and a containment bag system is expected to minimize this complication.

Human papillomavirus self‐sampling and urine‐sampling tests and the management and short‐term outcomes of cervical intraepithelial neoplasia: A prospective observational study

AbstractAimThe importance of human papillomavirus (HPV) co‐testing using physician‐, self‐, and urine‐collected samples to predict cervical intraepithelial neoplasia (CIN) grade 1–2 prognoses has not been previously reported. Therefore, this study aimed to investigate outcomes of patients with CIN 1–2 who simultaneously underwent physician‐, self‐, and urine‐collection sampling tests.MethodsThis study was conducted in Japan between October 2019 and November 2022 and examined the proportion of cases with CIN 1–2 progressions, the percentage of cases with persistent CIN 1–2, and the outcome differences according to the results of physician‐, self‐, and urine‐sampling tests.ResultsThere were 105 and 59 CIN 1 and 2 cases, respectively, with progression or persistence in 27 (29.3%) and 21 (50.0%) cases, respectively. The median follow‐up was 20 and 12 months, respectively. Progression and persistence of CIN 1 were significantly associated with HPV‐positive physician‐ and self‐collected samples. No significant difference was observed between cases with CIN 2 who had HPV‐positive and HPV‐negative results using any sampling method.ConclusionsPhysician‐ and self‐testing for HPV are crucial for predicting disease progression risk in CIN 1 cases. Future research with an extended observation period and consideration of the progression risks is warranted.

Comparative study on the mutation spectrum of L‐MYC and C‐MYC genes of blood cfDNA in patients with ovarian cancer and healthy females

AbstractBackgroundThis study aimed at detecting the mutations of L‐MYC and C‐MYC genes in ovarian cancer (OC) patients and healthy female volunteers using cell‐free DNA (cfDNA).MethodsWe evaluated cfDNA of 50 OC patients with different stages (I–IV) and 50 age‐matched healthy female volunteers (controls) in order to access mutations in exon‐1 of L‐MYC (198 bp) and exon‐3 of C‐MYC (165 bp) genes using Sanger sequencing.ResultsThe total mutations reported were 43 and 7 in exon‐1 of L‐MYC and exon‐3 of C‐MYC genes, respective. The C‐MYC and L‐MYC gene mutational status recorded in both cases and controls were compared with the already available data on mutations in c‐myc and L‐myc databases viz SNP db—NCBI, ClinVar db, COSMIC, PubMed, and LitVar which suggested that the detected mutations in exon‐1 of L‐MYC and exon‐3 of C‐MYC genes are novel.ConclusionOur study showed that cfDNA might be used for noninvasive detection of clinico‐genomic profiles of OC patients and as a prognostic biomarker for the disease.

Cervical cancer in Malaysia

AbstractCervical cancer is preventable due to effective screening to detect pre‐malignant lesion, and vaccination against its causative organism namely human papillomavirus (HPV). This review article described current situation of cervical cancer in Malaysia. There is decreasing cervical cancer incidence in the country, with age‐standardized rate of 10.3, versus 14.1 and 7.5 per 100 000 for worldwide and high‐income countries, respectively. School‐based HPV vaccination is part of national immunization since 2010, with yearly coverage rate of 83%–91%. The figure declined during coronavirus disease‐19 pandemic due to scarce vaccine supply and movement‐control order, resulting in about 500 000 students missing their course, with catch‐up program currently onboard. Opportunistic cervical screening program started in 1960s with cervical smear cytology, which is succeeded by HPV DNA screening since 2020. Cervical cytology remains indispensable  screening method in healthcare facility without access to HPV test kit, and used to triage high‐risk HPV positive with abnormal cytology that require urgent colposcopy. Computed tomography is the main imaging modality to assess local and distal extent of cervical cancer. Primary surgical treatment for early‐stage cancer is performed by trained gynecologic oncologist, with long waiting list for radiation therapy in locally advanced disease due to limited available public facility. There is restricted access to targeted therapy due to high treatment cost. In conclusion, Malaysia is heading toward cervical cancer elimination through rigorous investment in primary and secondary prevention, and increase in public engagement with the support of government policy enforcement.

Investigation of the clinical implications of anterior cervical invasion in locally advanced cervical squamous cell carcinoma

Abstract Purposes This study investigates the clinical significance of the anterior parametrical invasion in surgically treated patients with cervical squamous cell carcinoma (SCC). Methods We included patients diagnosed with cervical SCC with local lesions classified as T2b, who were treated at our department between January 2006 and December 2020. We evaluated the degree of anterior invasion using pretreatment magnetic resonance imaging and divided patients into three groups: partial, equivocal, and full invasion. The frequency of recurrence within 3 years (early recurrence) and overall prognosis were assessed. Results There were 12, 24, and 46 cases in the partial equivocal, and full invasion groups, respectively. Neoadjuvant chemotherapy followed by surgery and adjuvant chemotherapy was the mainstay of treatment across all groups (7, 17, and 27 cases, respectively). Although the frequency of early recurrence tended to be worse in the full group (partial; 2/7 cases, equivocal; 3/17 cases and full; 9/27 cases), all early local recurrence cases in the full group (four cases) responded well to the subsequent treatment. As for overall survival, the full invasion group had the best prognosis among the three groups. Conclusions In surgical treatment, although full anterior invasion may increase the risk of early local recurrence, it was considered to have little prognostic impact.

Pulmonary metastasectomy for recurrent metastatic ovarian cancer

AbstractAimThe prognosis of patients with ovarian cancer with lung metastasis is poor; data on pulmonary metastasectomy for such patients are lacking. This study aimed to determine the safety and feasibility of pulmonary resection as part of cytoreductive surgery for recurrent metastatic ovarian cancer.MethodsMedical records of patients with ovarian cancer, who underwent pulmonary resection for lung metastasis in our hospital from April 2012 to February 2022, were retrospectively reviewed.ResultsTen patients were included (median age, 53 years). Five patients had metastatic disease limited to the lungs. Additional surgeries included diaphragm resection, partial hepatectomy, para‐aortic lymph node dissection, and cytoreduction. We achieved complete cytoreduction for all patients without severe complications, and the 30‐day mortality was zero. After a median follow‐up of 23 months, four of the patients experienced recurrence. One patient recurred 9 months after the operation and was lost to follow‐up at 17 months, two died at 68 and 26 months respectively, one is alive with disease (23 months), and six are alive without recurrence, among whom two have survived for 56 and 124 months.ConclusionsPulmonary resection for recurrent metastatic ovarian cancer seems safe and feasible, with long‐term survival observed in certain patients. Pulmonary metastasectomy can be performed as part of the debulking surgery for selected patients with relapsed metastatic ovarian cancer. Both the patient lost to follow‐up and the one who died at 26 months, had two lung metastatic nodules and did not receive postoperative chemotherapy, which might have led to relatively poor prognosis.

A predictive study of genes related to lactic acid metabolism in cervical carcinoma

Abstract Objectives Lactic acid metabolism, a hallmark of carcinogenesis, may play potential roles in cervical carcinoma, assisting the prognosis prediction. Materials and Methods A regression analysis was conducted to identify the ones with the most frequent variation in mutations and CNV changes in lactate metabolism‐related (L‐related) genes, after which a prognostic nomogram was built based on selected genes and clinical features by machine learning methods. Results EGLN1 , IL1 , IL12RB1 , ENO1 , and 10 other genes had the most frequent changes and prognostic differences in overall survival (OS). The lactated associated risk (LAR) score model can distinguish the patients in OS ( p  = 0.046, HR = 101.9, 95%CI 1.1–9447.6), and together with clinical features has a higher AUC (AUC = 0.839). Furthermore, CD8 + T, activated CD4 + memory T and resting mast cells were significantly negatively associated with the LAR score. Conclusions Lactic acid metabolism is closely related to the prognosis of cervical carcinoma, where the immune microenvironment may play an important role.

The association between human papillomavirus infection, vaginal microecology, and cervical intraepithelial neoplasia in women from Xinjiang, China

AbstractPurposeThis study analyzes the relationship between human papillomavirus (HPV) infection, vaginal microecology, and cervical lesions to provide a basis for the prevention and treatment of cervical cancer (CC) in the Xinjiang region.MethodsReal‐time quantitative PCR was used for HPV genotyping and viral load. The Gram staining and dry biochemical enzyme kit were utilized to diagnose vaginal secretions. The χ2 test and Logistic regression analysis were used for statistical analysis.ResultsThe HPV infection rate among women in the Xinjiang region was 30.29%, of which the single HPV infection accounts for 77%. HPV16 and HPV52 were the main infection types. There was significant differences in the HPV infection rate and infection types among the Han, Uighur, Hui, and Kazakh ethnic groups. The viral load of HPV16 and HPV52 increases with the upgrade of cervical lesions. There were significant differences in vaginal microecology evaluation indicators H2O2, SNA, LE, GUS, trichomonas, clue cells, and lactobacilli among different ethnic groups. HPV negative patients with varying grades of cervical lesions exhibit a notable variance in H2O2 and LE, which is statistically significant. Single HPV infection and high viral load HPV significantly increase the risk of CC.ConclusionsThis study indicates that HPV infection and vaginal microecology differ among ethnic groups, which have a strong correlation with the progression of CC, offering guidance on CC screening and interventions in the Xinjiang area.

Serum CA125 level as predictors of the efficacy of olaparib maintenance therapy for platinum‐sensitive relapsed ovarian cancer

AbstractAimOvarian cancer is a gynecological malignancy with a poor prognosis. For platinum‐sensitive relapsed ovarian cancer, maintenance therapy with poly‐ADP ribose polymerase (PARP) inhibitors after chemotherapy is considered; however, olaparib treatment does not always lead to sufficient progression‐free survival (PFS). This study aimed to identify factors that predict the efficacy of maintenance therapy using olaparib in platinum‐sensitive relapsed ovarian cancer.MethodsTwenty‐seven patients with platinum‐sensitive relapsed ovarian cancer, who received initial treatment and showed complete or partial response to prior chemotherapy at our hospital, were included. The primary outcome was the time from the end of previous platinum‐based chemotherapy to disease progression (PFS). The Kaplan–Meier method was used to generate time‐to‐event curves for PFS; multivariate analysis was performed using the Cox proportional hazards regression model.ResultsThe median PFS was 12 months (95% confidence interval [CI]: 8.3–15.8). Before olaparib administration, the median PFS was 12 months in the <4.1 neutrophil‐to‐lymphocyte ratio group and 4 months in the ≥4.1 group, with PFS being significantly better in the <4.1 group (log‐rank: p = 0.023). When comparing serum cancer antigen 125 (CA125) levels, the median PFS was 13 months in the <18 U/mL group and 6 months in the >18 U/mL group (log‐rank: p = 0.022). Multivariate Cox regression analysis revealed that CA125 was the factor affecting PFS (hazard ratio: 4.85; 95% CI: 1.53–15.38).ConclusionsSerum CA125 levels at olaparib initiation in patients with platinum‐sensitive relapsed ovarian cancer may predict PFS as an effect of maintenance therapy using olaparib to treat recurrent disease.

Psychometric properties of the Turkish version of the Cervical Cancer Knowledge Scale

AbstractAimThis study aimed to investigate the psychometric properties of the Turkish adaptation of The Cervical Cancer Knowledge Scale (CCKS‐T). This scale was designed for the assessment of cervical cancer knowledge levels among women in the screening period.MethodsResearch was conducted with 307 women aged 21–65 years, who satisfied the eligibility criteria and agreed to participate. Data were collected via an online survey conducted during July and August 2023, utilizing both a Descriptive Information Form and the CCKS‐T. To confirm the validity of the scale, language and content validity assessments were conducted, in addition to confirmatory factor analysis. The scale's reliability was evaluated using Cronbach's alpha, item‐total correlation analysis, and a test–retest analysis. The scale consisted of eight items.ResultsThe content validity index of the scale items was found to be 1.0 with excellent sensitivity. Confirmatory factor analysis showed that the item factor loadings varied between 0.31 and 0.81 and the model had a good fit (x2/df = 2.200; GFI = 0.96; CFI = 0.96; RMSEA = 0.063). Cronbach's alpha of the Turkish version of the scale was found to be 0.80.ConclusionThe CCKS‐T demonstrates both validity and reliability as an instrument for the assessment of Turkish women's knowledge about cervical cancer.

A case of a blind‐ending right ureter first identified intraoperatively during total laparoscopic hysterectomy for uterine adenomyosis and fibroids in a woman with severe ipsilateral kidney hypoplasia

AbstractDetecting ureteral injury—a serious intraoperative and postoperative complication of hysterectomy—is a high level of difficulty if ureteral malformations are not identified preoperatively. A 39‐year‐old Japanese woman underwent total laparoscopic hysterectomy for uterine adenomyosis. During surgery, ureteral peristalsis was absent on the right side, whereas the left ureter was visible under the peritoneum. Transabdominal ultrasonography failed to locate the right kidney, with cystoscopy showing no flow from the right ureteral orifice. The ureteral tunnel was identified by tracing the vascular path of the internal iliac and uterine arteries, confirming that the corded tissue was the right ureter. Postoperative contrast‐enhanced CT revealed severe right kidney atrophy with no contrast effect or connected ureter. Based on intraoperative laparoscopy and postoperative examination, a diagnosis of a unilateral ureteral scar with a proximal blind end and ipsilateral renal dysgenesis was established, marking the first reported instance of endoscopic visualization of this anomaly. In addition to normal pelvic anatomy, surgeons must consider embryological abnormalities to prevent intraoperative complications.

Prediction of benign and malignant ovarian tumors using Resnet34 on ultrasound images

AbstractObjectiveTo develop deep learning (DL) prediction models using transvaginal ultrasound (TVS), transabdominal ultrasound (TAS), and color Doppler flow imaging (CDFI) of TVS (CDFI_TVS) to automatically predict benign or malignant ovarian tumors.MethodsThis retrospective study included women with ovarian tumors who underwent ultrasound between August 2018 and October 2022. Histopathological analysis was used as a reference standard. The dataset was preprocessed by clipping, flipping, and rotating images to generate a larger, more complicated, and diverse dataset to improve accuracy and generalizability. The dataset was then divided into training (80%) and test (20%) sets. The weights of the models, modified from the residual network (ResNet) with the TVS, TAS, and CDFI_TVS images (hereafter, referred to as DLTVS, DLTAS, and DLCDFI_TVS, respectively) were developed. The area under the receiver operating characteristic curve (AUC) analysis in the test set was used to compare the predictive value of DL for malignancy.ResultsA total of 2340 images from 1350 women with adnexal masses were included. DLTVS had an AUC of 0.95 (95% CI: 0.93–0.97) for classifying malignant and benign ovarian tumors, comparable with that of DLTAS (AUC, 0.95; 95% CI: 0.91–0.98; p = 0.96) and DLCDFI_TVS (AUC, 0.88; 95% CI: 0.84–0.93; p = 0.02). Decision curve analysis indicated that DLTVS performed better than DLTAS and DLCDFI_TVS.ConclusionWe developed DL models based on TVS, TAS, and CDFI_TVS on ultrasound images to predict benign and malignant ovarian tumors with high diagnostic performance. The DLTVS model had the best prediction compared with the DLTAS and DLCDFI_TVS models.

AEBP1 upregulation contributes to cervical cancer progression by facilitating cell proliferation, migration, and invasion

Abstract Background Aberrant expression of adipocyte enhancer‐binding protein 1 (AEBP1) has been demonstrated to be involved in the tumorigenesis and progression of numerous cancers. This study was aimed to investigate the mechanism of AEBP1 in the development of cervical cancer. Methods The expression of AEBP1 in cervical cancer was assessed by immunohistochemistry. The function of AEBP1 on cell proliferation, migration, and invasion was determined by methyl thiazolyl tetrazolium assay, colony formation, and transwell assay. The activation of related signaling pathway was determined by western blot. The bioinformatics analysis was performed by Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis. Results Higher protein expression of AEBP1 was observed in patients with cervical cancer. Overexpressed AEBP1 promoted cell proliferation, migration, and invasion abilities in cervical cancer cells. Moreover, the research manifested that AEBP1 activated the phosphorylation of STAT3. GO and KEGG analysis showed that genes positively related to AEBP1 were highly enriched in functions like epithelial cell proliferation, muscle cell migration, myoblast migration, smooth muscle tissue development, ECM–receptor interaction, transcriptional misregulation in cancer, and proteoglycans in cancer. While genes negatively related to AEBP1 were associated with immunity, including inflammatory response, external‐stimulus response, neutrophil, granulocyte, and macrophage chemotaxis. Conclusions This study suggested that AEBP1 acts as an oncogened and might be a potential therapeutic target for the treatment of cervical cancer.

Prediction of the survival of patients with advanced‐stage ovarian cancer patients undergoing interval cytoreduction with the use of computed tomography reevaluation after neoadjuvant chemotherapy

AbstractPurposeTo predict ovarian cancer patients' survival by computed tomography (CT) reevaluation after neoadjuvant chemotherapy.Patients and MethodsIn this retrospective single‐center cohort study, all patients with advanced epithelial ovarian cancer underwent platinum‐based chemotherapy followed by interval cytoreductive surgery. Assessment of abdominal and pelvic lesions before and after chemotherapy using CT scoring criteria. Meanwhile, the progression‐free survival and overall survival times were obtained. The Kaplan–Meier method was used to estimate survival curves. Univariate analysis of continuous and categorical variables was performed for prognostic significance using the Cox proportional hazards model. Variables with p < 0.10 on univariate analysis were then included in a multivariate forward stepwise Cox regression analysis.ResultsA total of 162 patients were included, with a median age of 52 years (range, 20–72 years). One hundred seven patients (66.0%) underwent suboptimal cytoreduction, and there was no statistically significant difference in patient survival between surgical procedures (log‐rank p = 0.092). Six radiographic features were hazard factors for suboptimal cytoreduction. Four features in the postchemotherapy CT images were assigned as predictive criteria by the stepwise regression model (area under the curve [AUC] = 0.689). As compared with a higher AUC (0.713) in the model involving two clinical variables (age and postsurgery CA‐125) and two postchemotherapy CT features, the model considering the CT score changes before and after chemotherapy had the highest diagnostic accuracy (AUC = 0.843).ConclusionCT reevaluation after neoadjuvant chemotherapy is essential for ovarian cancer, the changes of CT feature and score are potential great tools to predict patient survival.

A case of ovarian carcinosarcoma with a germline pathogenic variant of BRCA2 involving a perforated appendix with an abscess

AbstractWe report a case of rare and aggressive ovarian carcinosarcoma with a germline pathogenic BRCA2 variant. A patient with a history of breast cancer who developed an inflammatory ovarian tumor with peritonitis carcinomatosis involving the appendix suffered from cachexia. Following three cycles of weekly paclitaxel and carboplatin chemotherapy, emergency surgery was required owing to sepsis. Bilateral salpingo‐oophorectomy, total hysterectomy, appendectomy, and small intestine adhesiolysis were performed. Histologically, the tumor comprised an admixture of carcinomatous and sarcomatous components, with involvement of the appendix, which had caused perforation and abscess formation. The final diagnosis was ovarian carcinosarcoma with a germline pathogenic BRCA2 variant, c.658_659del (p.Val220fs). The patient responded completely to adjuvant chemotherapy. A combination of chemotherapy and surgery might be beneficial to patients with ovarian carcinosarcoma and germline pathogenic BRCA2 variants with a poor general condition. This is the first report of ovarian carcinosarcoma with a germline pathogenic BRCA2 variant that responded favorably to chemotherapy.

Identification of N1 methyladenosine‐related biomarker predicting overall survival outcomes and experimental verification in ovarian cancer

AbstractAimThis study aimed to construct a N1‐methyladenosine (m1A)‐related biomarker model for predicting the prognosis of ovarian cancer (OVCA).MethodsOVCA samples were clustered into two subtypes using the Non‐Negative Matrix Factorization (NMF) algorithm, including TCGA (n = 374) as the training set and GSE26712 (n = 185) as the external validation set. Hub genes, which were screened to construct a risk model, and nomogram to predict the overall survival of OVCA were explored and validated through various bioinformatic analysis and quantitative real‐time PCR.ResultsFollowing bootstrap correction, the C‐index of nomogram was 0.62515, showing reliable performance. The functions of DEGs in the high‐ and low‐risk groups were mainly enriched in immune response, immune regulation, and immune‐related diseases. The immune cells relevant to the expression of hub genes were explored, for example, Natural Killer (NK) cells, T cells, activated dendritic cells (aDC).ConclusionsAADAC, CD38, CACNA1C, and ATP1A3 might be used as m1A‐related biomarkers for OVCA, and the nomogram labeled with m1A for the first time had excellent performance for predicting overall survival in OVCA.

Mini‐review: Immunology in ovarian cancer

AbstractImmunotherapy for ovarian cancer has been studied for many years and programmed cell death protein 1 ligand/programmed cell death protein 1 (PD‐L1/PD‐1) blockade has been attempted in several clinical trials; however, the expected therapeutic effect has not been achieved. In contrast, the PD‐L1/PD‐1 blockade has been clinically applied to endometrial and cervical cancers, and a certain therapeutic effect has been observed. In endometrial cancer, promising outcomes have been achieved with a combination of an anti‐PD‐1 antibody and lenvatinib, regardless of the number of regimens, even in cases of recurrence after platinum administration. Therefore, immunotherapy is expected to have a therapeutic effect on ovarian cancer regardless of platinum resistance. In this review, considering immunotherapy for ovarian cancer, we discuss the immune mechanisms that exist in ovarian cancer and the immunotherapeutic strategies that should be developed.

Identification and validation of shared genes and key pathways in endometriosis and endometriosis‐associated ovarian cancer by weighted gene co‐expression network analysis and machine learning algorithms

AbstractBackgroundEpidemiological studies reported that patients with endometriosis had an increased risk of developing endometriosis‐associated ovarian cancer (EAOC). The present study aimed to identify shared genes and key pathways that commonly interacted between EAOC and endometriosis.MethodsThe expression matrix of ovarian cancer and endometriosis were collected from the Gene Expression Omnibus database. The weighted gene co‐expression network analysis (WGCNA) was used to construct co‐expression gene network. Machine learning algorithms were applied to identify characteristic genes. CIBERSORT deconvolution algorithm was used to explore the difference in tumor immune microenvironment. Furthermore, diagnostic nomogram was constructed and evaluated for supporting clinical practicality.ResultsWe identified 262 shared genes between EAOC and endometriosis via WGCNA analysis. They were mainly enriched in cytokine–cytokine receptor interaction. After protein–protein interaction network and machine learning algorithms, we recognized two characteristic genes (EDNRA, OCLN) and established a nomogram that presented an outstanding predictive performance. The hub genes demonstrated remarkable associations with immunological functions. Survival analysis indicated that dysregulated expressions of EDNRA and OCLN were closely correlated with prognosis of ovarian cancer patients. gene set enrichment analyses revealed that the two characteristic genes were mainly enriched in the cancer‐ and immune‐related pathways.ConclusionOur findings pave the way for further investigation of potential candidate genes and will aid in improving the diagnosis and treatment of EAOC in endometriosis patients. More research is required to determine the exact mechanisms by which these two hub genes affecting the development and progression of EAOC from endometriosis.

SIK2: A critical glucolipid metabolic reprogramming regulator and potential target in ovarian cancer

AbstractAimTo explore the role of salt‐inducible kinase 2 (SIK2) on glucose and lipid metabolism in ovarian cancer (OC), so as to increase the understanding of potential inhibitors targeting SIK2 and lay a foundation for future precision medicine in OC patients.MethodsWe reviewed and summarized the regulation effect of SIK2 on glycolysis, gluconeogenesis, lipid synthesis, and fatty acids β‐oxidation (FAO) in OC, as well as the potential molecular mechanism and the prospects of potential inhibitors targeting SIK2 in future cancer treatments.ResultsMany pieces of evidence show that SIK2 is closed associated with glucose and lipid metabolism of OC. On the one hand, SIK2 enhances the Warburg effect by promoting glycolysis and inhibiting oxidative phosphorylation and gluconeogenesis, on the other hand, SIK2 regulates intracellular lipid metabolism through promoting lipid synthesis and FAO, all of which ultimately induces growth, proliferation, invasion, metastasis, and therapeutic resistance of OC. On this basis, SIK2 targeting may become a new solution for the treatment of a variety of cancer types including OC. The efficacy of some small molecule kinase inhibitors has also been demonstrated in tumor clinical trials.ConclusionSIK2 displays significant effects in OC progression and treatment through regulating cellular metabolism including glucose and lipid metabolism. Therefore, future research needs to further explore the molecular mechanisms of SIK2 in other types of energy metabolism in OC, based on this to develop more unique and effective inhibitors.

Rosline promotes p21 expression to inhibit ovarian cancer cell proliferation via p53‐independent pathway

AbstractAimTo investigate the effect of benzothiazole derivatives (Rosline) on ovarian cancer and the potential mechanism.MethodsOvarian cancer tissues were collected clinically and immunohistochemistry was used to detect the expression of p53 and p21. Ovarian cancer cells were exposed to 0, 2.5, 5, 10 μmol/L Rosline for 24 h. 100 nmol/L Pifithrin‐α pre‐incubation was used to inhibit the transcriptional activity of p53. CCK‐8 and BrdU assays were used to detect the effects of different concentrations of rosline on the proliferation and cell cycle of OVCAR420 and SKOV3 cells. Flow cytometry assay was used to detect cell cycle. The transcriptional and translational expression of p21 and p53 were detected by RT‐qPCR and Western blot.Resultsp21 was expressed in ovarian cancer tissues without p53 expression. Rosline inhibits the proliferation of ovarian cancer cells and blocks the cell cycle progression. Meanwhile, Rosline promotes p21 expression in ovarian cancer cells at both mRNA and protein levels, but with no significant effect on p53 expression. Besides, Rosline promotes p21 expression, inhibits cell proliferation, and blocks the cell cycle via the p53‐independent pathway.ConclusionRosline promoted p21 expression thereby inhibiting cell proliferation and blocks the cell cycle via p53‐independent pathway.

Comparison of the efficacy and safety of total laparoscopic hysterectomy without and with uterine manipulator combined with pelvic lymphadenectomy for early cervical cancer

AbstractObjectiveSome studies have reported that the prognosis of total laparoscopic hysterectomy (TLH) for early‐stage cervical cancer (CC) is worse than that of open surgery. And this was associated with the use of uterine manipulator or not. Therefore, this study retrospectively analyzes the efficacy and safety of TLH without uterine manipulator combined with pelvic lymphadenectomy for early‐stage CC.MethodsFifty‐eight patients with CC (stage IB1‐IIA1) who received radical hysterectomy from September 2019 to January 2020 were divided into no uterine manipulator (n = 26) and uterine manipulator group (n = 32). Then, clinical characteristics were collected and intraoperative/postoperative related indicators were compared.ResultsPatients in the no uterine manipulator group had significantly higher operation time and blood loss than in the uterine manipulator group. Notably, there was no significant difference in hemoglobin change, blood transfusion rate, number of pelvic nodules, anal exhaust time, complications and recurrence rate between the two groups. Additionally, patients in the uterine manipulator group were prone to urinary retention (15.6%) and lymphocyst (12.5%), while the no uterine manipulator group exhibited high probability of bladder dysfunction (23.1%) and urinary retention (15.4%). Furthermore, the 1‐year disease‐free survival rate and the 1‐year overall survival rate were not significantly different between the two groups.ConclusionThere was no significant difference in the efficacy and safety of TLH with or without uterine manipulator combined with pelvic lymphadenectomy in the treatment of patients with early‐stage CC. However, the latter requires consideration of the negative effects of high operation time and blood loss.

Identification of predictive biomarkers for diagnosis and radiation sensitivity of uterine cervical cancer using wide‐targeted metabolomics

AbstractAimUterine cervical cancer (UCC) is the fourth most common cancer in women, responsible for more than 300 000 deaths worldwide. Its early detection, by cervical cytology, and prevention, by vaccinating against human papilloma virus, greatly contribute to reducing cervical cancer mortality in women. However, penetration of the effective prevention of UCC in Japan remains low. Plasma metabolome analysis is widely used for biomarker discovery and the identification of cancer‐specific metabolic pathways. Here, we aimed to identify predictive biomarkers for the diagnosis and radiation sensitivity of UCC using wide‐targeted plasma metabolomics.MethodsWe analyzed 628 metabolites in plasma samples obtained from 45 patients with UCC using ultra‐high‐performance liquid chromatography with tandem mass spectrometry.ResultsThe levels of 47 metabolites were significantly increased and those of 75 metabolites were significantly decreased in patients with UCC relative to healthy controls. Increased levels of arginine and ceramides, and decreased levels of tryptophan, ornithine, glycosylceramides, lysophosphatidylcholine, and phosphatidylcholine were characteristic of patients with UCC. Comparison of metabolite profiles in groups susceptible and non‐susceptible to radiation therapy, a treatment for UCC, revealed marked variations in polyunsaturated fatty acid, nucleic acid, and arginine metabolism in the group not susceptible to treatment.ConclusionsOur findings suggest that the metabolite profile of patients with UCC may be an important indicator for distinguishing these patients from healthy cohorts, and may also be useful for predicting sensitivity to radiotherapy.

Immature teratoma arising from uterine corpus in an 11‐year‐old girl: Case report and review of the literature

AbstractTeratomas are one of the most common germ cell tumors, and they usually occur in ovaries. Extragonadal teratomas are rare, especially immature ones. Only several cases of primary teratomas of the uterus have been reported since 1929. Here, the case of an 11‐year‐old patient who had a 6‐month history of sustained abnormal vaginal discharge is presented. Transabdominal ultrasonography revealed a solid mass in her uterus, resulting in the patient undergoing surgery. Examination of PET‐CT scans revealed a mass in the right ovary of the patient 20 days after surgery. The patient underwent a second surgery followed by chemotherapy. This is the youngest case among reported patients of primary immature uterine teratoma, and this patient showed no evidence of recurrence during 2 years of follow‐up.

Perioperative outcomes in patients with very low‐risk endometrial cancer undergoing surgery without lymph node dissection: Results from KGOG 2021

AbstractAimTo evaluate the perioperative outcomes of patients with endometrial cancer meeting the Korean Gynecologic Oncology Group (KGOG) criteria who underwent surgery without lymph node dissection.MethodsThis study included 153 patients who met the KGOG criteria: (1) endometrioid histology, (2) myometrial invasion <50%, (3) tumor confined to the corpus, (4) no lymph node >1 cm, and (5) serum CA125 ≤ 35 U/mL. The patients underwent surgery without lymph node dissection at 11 hospitals in Korea between February 2020 and May 2024. Perioperative outcomes were collected prospectively.ResultsAmong the 153 patients, 89 (58%) underwent surgery without lymph node removal, while 64 (42%) underwent surgery with lymph node removal. Minimally invasive surgery was performed in >90% of cases, with a conversion rate to laparotomy of 1%. The mean surgery time was 109.37 ± 37.67 min. Estimated blood loss was minimal (93.74 ± 93.13 mL), with a mean hemoglobin drop of 1.32 ± 1.01 g/dL. Transfusions were required in only three patients (2%). Postoperative hospital stays exceeded 2 days in 51% of cases. Lymph node metastasis was observed in just one case (1%). Adverse events included 52 grade 1 and 2 grade 2 events (e.g., headache, paresthesia). Patients undergoing lymph node removal (primarily sentinel lymph node biopsy) had significantly longer surgery times and postoperative hospital stays compared to those without lymph node removal.ConclusionSurgery without lymph node dissection demonstrated excellent perioperative outcomes and minimal adverse events in patients meeting KGOG criteria.

Feasibility of anticancer treatment using scalp cooling for patients with gynecological cancer in Japan: A case series study

AbstractAimTo evaluate the safety and efficacy of scalp cooling in preventing chemotherapy‐induced alopecia among Japanese patients with gynecological cancer.MethodsA retrospective study was conducted involving 16 patients with gynecological cancer who underwent chemotherapy with scalp cooling at our institution between January 2021 and April 2024. The completion rate of the planned regimens, the success rate (defined as hair loss ≤50%), hair volume recovery 8–12 weeks after chemotherapy, and adverse events were assessed. Additionally, patient satisfaction was measured using the net promoter score (NPS) following chemotherapy completion.ResultsOf the 16 patients included in the study, chemotherapy regimens comprised six courses of combination therapy with paclitaxel plus carboplatin in 11 cases, three courses of the same regimen in three cases, and three courses of combination therapy with docetaxel plus carboplatin in two cases. The overall completion rate of the planned regimens was 75% (12/16 cases). Among the 12 cases, nine were evaluable for alopecia, with a success rate of 33.3%. The proportion of the patients who recovered hair volume from ≤50% to >50% was 83.3% in the occipital region. Adverse events were reported as follows: chills in 75.0%, jaw pain in 68.8%, headache in 31.3%, nausea in 18.8%, and hypertension and hunger in 12.5% each. The NPS for scalp cooling was 26.7 points.ConclusionScalp cooling is effective and safe in preventing hair loss and restoring hair volume in Japanese patients with gynecological cancer, suggesting high patient satisfaction with this treatment.

Assessment of magnetic resonance imaging findings in ovarian granulosa cell tumors along with clinical prognostic factors

AbstractAimTo determine the role of preoperative MRI in the diagnosis and treatment of patients with granulosa cell tumors (GCTs) of the ovary.Materials and MethodsTwenty‐four patients who were operated on between 2018 and 2022 and who were pathologically diagnosed with GHT and met the inclusion criteria were retrospectively examined. The findings were compared with the patients' demographic data, symptoms, surgical findings (laterality, stage, lymph node involvement, endometrial pathology, tumor size), and CA‐125 levels.ResultsThe final cohort included 24 patients with a mean age of 54.71 ± 16.52. All the patients had the pathological diagnosis of adult type GCT. In the morphological evaluation, the most common finding was a solid‐cystic mixed type (14 patients, 58.3%), while intratumoral hemorrhage signal was observed in 10 patients (41.7%). In the majority of cases (91.7%), the mass showed regular contours. The honeycomb/Swiss cheese sign was detected in 54.2% of the cases. When the T1 and T2 signal of the solid component of the mass were examined relative to the myometrium, the majority of GCTs appeared isointense on both sequences (83.3% and 62.5%, respectively). The mean ADC value of the solid component obtained from diffusion‐weighted imaging was 0.78 ± 0.15 × 10−3. Pelvic fluid was observed in 41.7% of the cases. The average endometrial thickness was 9.74 ± 6.43 mm. Thickened endometrium more than 9 mm was observed in 9 out of the remaining 21 patients (42.9%).ConclusionUnderstanding the key imaging features for GCTs plays an essential role in the diagnosis and guiding the treatment effectively.

A case of ovarian serous cystadenofibroma with scattered lesions in pelvic cavity, like malignant disseminations

AbstractOvarian serous cystadenofibroma is a relatively rare subtype of serous cystadenoma classified as ovarian benign epithelial tumor. We report a rare case of ovarian serous cystadenofibroma with scattered lesions in pelvic cavity, like malignant disseminations. The patient was 22 years old, gravida 0, para 0. In the laparoscopic surgery, numerous hard yellowish‐white solid masses of various sizes were present in the bilateral ovaries. Grossly similar masses were scattered in the fimbria of the fallopian tubes, peritoneum, and great omentum. Because the intraoperative rapid histological diagnosis was benign tumor, surgery was completed for only tumor excision. Postoperative histopathological diagnosis is serous cystadenofibroma. Similar pathological findings were noted in the scattered lesions in the peritoneum and great omentum. No malignant or borderline malignant finding was observed. Because of a benign disease, careful treatment taking fertility preservation into consideration is necessary, especially for young patients.

Mechanical dilatation of the stenosed cervix under local anesthesia: A prospective case series

AbstractAimCervical stenosis is traditionally managed by mechanical dilatation under general anesthesia (GA). We aimed to assess the safety, effectiveness, and patient acceptability of dilatation in the outpatient setting under local anesthesia (LA).MethodsData were collected prospectively from all patients attending the outpatient department with cervical stenosis from March 20, 2015 to September 23, 2020. Mechanical dilatation of the cervix was performed using Hegar dilators under LA. Subsequent colposcopic assessment, cytology, histology, and management were recorded.ResultsOne hundred forty‐nine cases were referred for cervical dilatation, 63 (43%) of which had complete stenosis. One hundred eighteen (79%) patients had previously undergone cervical procedures. Successful dilatation under LA was achieved in 119 (83%) patients; 5 (3%) declined (requesting GA), 6 (4%) did not tolerate speculum examination, and 19 (13%) had unsuccessful procedures. The median Hegar size used was 8 mm. Dilatation under LA was acceptable in 93% attempted procedures. Thirteen episodes of restenosis were recorded with no major adverse events. Younger age (p = 0.045) and severe (compared to complete) stenosis (p < 0.0001) were associated with procedure success, with improved results over time (p = 0.003). Successful dilatation permitted cervical assessment; eight patients required cervical excisions, two underwent hysterectomies, with one confirmed case of adenocarcinoma.ConclusionRigid cervical dilatation in the outpatient setting provides effective, instantaneous treatment for women who have failed cytological or colposcopic assessment. For the vast majority of women, the procedure was well tolerated and preferred to using GA. However, given that 1 in 10 women experienced restenosis, patients should be counseled about the possibility of requiring further management.

Real‐world clinical outcomes of patients with high‐risk endometrial cancer or endometrial carcinosarcoma in England: A retrospective cohort study

Abstract Aim The objectives of this study were to describe patient characteristics and estimate real‐world disease‐free survival (rwDFS) and overall survival (OS) from initiation of first adjuvant therapy among patients with high‐risk endometrial cancer (EC) in England. Methods This was a retrospective cohort study based on data from Public Health England's National Cancer Registration and Analysis Service (NCRAS) between 2014 and 2023. Adult women with EC or endometrial carcinosarcoma at high risk of recurrence who received adjuvant therapy within 90 days after surgery were eligible for inclusion. We operationalized rwDFS as time to next treatment or death. Results In total, 6036 women (mean age: 67 years; 86% White) were eligible for inclusion, with a mean follow‐up of 48 months. During the study period, 45% of patients experienced recurrence and 39% of patients died due to any cause. Median rwDFS and OS from initiation of adjuvant therapy were estimated at 4.56 years (95% CI: 4.14–5.12) and 8.85 years (95% CI: 8.15–9.82), respectively. Estimated 2‐year and 5‐year probabilities were 0.64 (95% CI: 0.63–0.65) and 0.49 (95% CI: 0.48–0.50) for rwDFS, and 0.78 (95% CI: 0.77–0.79) and 0.60 (95% CI: 0.58–0.61) for OS, respectively. Disease recurrence was associated with a 3.23‐fold higher risk of death ( p  < 0.001). Kendall's τ correlation coefficient between rwDFS and OS was 0.75 (95% CI: 0.69–0.80, p  < 0.001). Conclusions The results from our study underscore the substantial clinical burden and unmet medical need of women with high‐risk EC and the validity of rwDFS as a surrogate for OS.

Potential drug repurposing of ruxolitinib to inhibit the JAK/STAT pathway for the treatment of patients with epithelial ovarian cancer

AbstractAimThis review aimed to describe the potential for therapeutic targeting of the JAK/STAT signaling pathway by repurposing the clinically‐approved JAK inhibitor ruxolitinib in the patients with epithelial ovarian cancer (OC) setting.MethodsWe reviewed publications that focus on the inhibition of the JAK/STAT pathway in hematological and solid malignancies including OC.ResultsPreclinical studies showed that ruxolitinib effectively reduces OC cell viability and metastasis and enhances the anti‐tumor activity of chemotherapy drugs. There are a number of recent clinical trials exploring the role of JAK/STAT inhibition in solid cancers including OC. Early results have not adequately supported efficacy in solid tumors. However, there are preclinical data and clinical studies supporting the use of ruxolitinib in combination with both chemotherapy and other targeted drugs in OC setting.ConclusionInflammatory conditions and persistent activation of the JAK/STAT pathway are associated with tumourigenesis and chemoresistance, and therapeutic blockade of this pathway shows promising results. For women with OC, clinical investigation exploring the role of ruxolitinib in combination with chemotherapy agents or other targeted therapeutics is warranted.

Ovarian cancer: Novel mechanisms and therapeutic targets regarding the microenvironment in the abdominal cavity

AbstractOvarian cancer is an intractable disease that is mostly diagnosed at an advanced stage and has a high recurrence rate. The early development of characteristic peritoneal dissemination via ascites contributes to a poor prognosis. Based on the “seed and soil” theory, ovarian cancer is considered to form a disseminated tumor that interacts with the peritoneum; superficial mesothelial cells are structurally important. Thus far, we have reported that peritoneal mesothelial cells, which originally are ecological defenses, transform into ovarian cancer‐associated mesothelial cells, which are allies of cancer. They are found to be actively involved in the formation of a friendly “soil” that promotes the survival of “seeds” of ovarian cancer cells. We also demonstrated that the progression of ovarian cancer and the induction of its refractory nature are partially mediated through competition and cooperation between ovarian cancer and mesothelial cells. We believe that it is necessary to shift the aim of treatment strategies from solely targeting cancer cells to focusing on the crosstalk between the surrounding environment and ovarian cancer, an approach that ultimately aims to achieve “coexistence” with cancer through disease control.

Epidemiology of cervical cancer and HPV infection in Asia and Oceania

AbstractCancer will continue to be a major source of morbidity and mortality globally during the foreseeable future. Human papillomavirus (HPV)‐related cancer is now a serious problem in both women and men. The most common HPV‐related cancer is cervical cancer in females and oropharyngeal cancer in males. Eastern Africa has a high age‐standardized incidence of HPV‐related cancers, followed in order by Southern Africa, Central Africa, and then the rest of Africa. Among Asian and Oceania countries, Fiji, Papua New Guinea, Solomon Islands, Indonesia, Maldives, and Myanmar have extremely high age‐standardized incidences and mortality. Oropharyngeal cancer is less common than cervical cancer, but the age‐standardized incidence, for both females and males, is higher in Western Europe, Northern Europe, North America, and Australia/New Zealand. Oropharyngeal cancer incidence rates differ significantly from the rates of cervical cancer within the same countries. In Asia and Oceania, the incidence of oropharyngeal cancer is particularly high among females in Bhutan, Bangladesh, and Australia, and it is highest among males in Bangladesh, New Caledonia, Australia, and French Polynesia. To a certain extent, cervical cancer can be reduced through the development of cervical screening programs and improvements in screening uptake. On the other hand, for oropharyngeal cancer, as of yet, no effective means of cancer screening has been established. Widespread uptake of HPV vaccine will contribute to the reduction of HPV‐related cancers in Asia and Oceania, but also in the rest of the world.

Marked urinary retention: Potentially misleading gynecologists into diagnosing the condition as a giant ovarian cyst

A retrospective analysis of secondary cytoreductive surgery plus hyperthermic intraperitoneal chemotherapy in patients with recurrent ovarian cancer

AbstractAimTo evaluate the effect of secondary cytoreductive surgery (SeCRS) plus hyperthermic intraperitoneal chemotherapy (HIPEC) in recurrent epithelial ovarian cancer patients.MethodsThis retrospective study analyzed a prospective database. We collected information of 389 patients who were diagnosed with recurrent epithelial ovarian cancer. All patients underwent SeCRS with or without HIPEC. Overall survival and progression‐free survival (PFS) were used to evaluate the treatment effectiveness.ResultsOf the 389 patients collected, 123 underwent primary or interval cytoreductive surgery at initial treatment and SeCRS at recurrence (Group A), 130 underwent primary or interval cytoreductive surgery at initial and SeCRS plus HIPEC at recurrence (Group B), and 136 underwent primary or interval cytoreductive surgery plus HIPEC at initial and SeCRS plus HIPEC at recurrence (Group C). The median overall survival for Groups A, B, and C were 49.1 months (95% confidence interval [CI]: 47.6–50.5), 56.0 months (95% CI: 54.2–57.7), and 64.4 months (95% CI: 63.1–65.6), respectively. The median PFS for Groups A, B, and C were 13.1 months (95% CI: 12.6–13.5), 15.0 months (95% CI: 14.2–15.7), and 16.8 months (95% CI: 16.1–17.4), respectively. There were no significant difference in incidence and grade of adverse events among groups.ConclusionsThis study suggested that SeCRS plus HIPEC followed by chemotherapy resulted in longer overall survival and PFS than only SeCRS followed by chemotherapy in patients with recurrent ovarian cancer, especially in patients who were treated with repeat HIPEC.

Neuroendocrine carcinoma of the uterine cervix with extensive pagetoid spread pattern

AbstractThere have been no reported cases of neuroendocrine carcinoma (NEC) of the cervix with pagetoid spread (Pag‐S). A 44‐year‐old woman came to our department because of abnormal cytology that persisted immediately after a radical hysterectomy for NEC of the cervix. A mapping biopsy in a large area from the vaginal wall to the vulva revealed that synaptophysin/Ki‐67‐positive tumor cells were scattered within the epithelium in multiple areas, suggesting a wide Pag‐S of NEC. Because tumor cells were found beyond the vaginal wall, the anterior pelvic exenteration was performed. Since we could pathologically confirm the complete resection and no distant metastases were detected, no adjuvant therapy was performed. Four years have passed since the initial treatment without any tumor recurrence. It is known that the prognosis of NEC of the cervix that invades beyond the cervix is poor; however, if there is a Pag‐S pattern, a radical surgical treatment can be considered.

Pseudo‐pseudo Meigs syndrome in systemic lupus erythematosus misdiagnosed as pseudo‐Meigs' syndrome: A case report

AbstractSymptoms of pelvic masses, elevated serum CA125 levels, massive ascites, and pleural effusion in female patients are usually associated with malignancy. Some benign ovarian tumors or other nonmalignant tumors may also produce similar symptoms, called Meigs syndrome or pseudo‐Meigs' syndrome, which should be one of the differential diagnoses. However, there is an extremely rare form of SLE called pseudo‐pseudo Meigs syndrome (PPMS), which may also present with the above symptoms, but is not associated with any of the tumors. In this paper, we report a case of a 47‐year‐old woman who presented with abdominal distention. The patient was found to have elevated serum CA125 levels to 182.9 U/mL before the operation. Her PET‐CT suggested a large heterogeneous mass in the pelvis measuring 8.2 × 5.8 cm with a large amount of ascites. She was initially diagnosed with ovarian cancer and underwent exploratory laparotomy. Pathology of the surgical specimen revealed a uterine leiomyoma. Two months after discharge, the patient's ascites reappeared along with recurrent intestinal obstruction. After ascites and serological tests, she was eventually diagnosed with systemic lupus erythematosus and received systemic hormonal therapy.

Efficacy and safety of apatinib combined with liposomal doxorubicin or paclitaxel versus liposomal doxorubicin or paclitaxel monotherapy in patients with recurrent platinum‐resistant ovarian cancer

AbstractAimApatinib is an effective treatment for patients with gynecological cancers. This study aimed to further explore the efficacy and safety of apatinib plus chemotherapy in patients with recurrent platinum‐resistant ovarian cancer (PROC).MethodsTotally, 105 patients with recurrent PROC receiving apatinib plus chemotherapy (N = 51) and chemotherapy alone (N = 54) were retrospectively enrolled in this cohort study.ResultsObjective response rate (37.3% vs. 14.8%) (p = 0.009) and disease control rate (80.4% vs. 61.1%) (p = 0.030) were increased in the apatinib plus chemotherapy group versus the chemotherapy group. The median (95% confidence interval [CI]) progression‐free survival (PFS) and overall survival (OS) were 5.5 (3.4–7.6) and 21.4 (16.2–26.6) months in the apatinib plus chemotherapy group, and they were 3.8 (3.0–4.6) and 14.8 (11.9–17.7) months in the chemotherapy group. Meanwhile, the Kaplan–Meier curves revealed that PFS (p = 0.008) and OS (p = 0.012) were prolonged in the apatinib plus chemotherapy group versus the chemotherapy group. This finding was confirmed by multivariate Cox's proportional regression analyses: enter method (hazard ratio [HR] = 0.515, p = 0.007 for PFS; HR = 0.222, p < 0.001 for OS) and step‐forward method (HR = 0.608, p = 0.019 for PFS; HR = 0.346, p = 0.001 for OS). Additionally, the incidence of hypertension was increased in the apatinib plus chemotherapy group versus the chemotherapy group (p = 0.038), while others were not different between the two groups (all p > 0.05). Grades 3 and 4 adverse events were neutropenia, hypertension, leukopenia, hand–foot syndrome, nausea and vomiting, fatigue, thrombocytopenia, and anemia in the apatinib plus chemotherapy group.ConclusionApatinib combined with chemotherapy is a superior choice over chemotherapy alone for recurrent PROC management.

Comparison of older and younger patients with ovarian cancer: A post hoc study (JGOG3016‐A3) of the treatment strength and prognostic outcomes of conventional or dose‐dense chemotherapy

AbstractAimTo evaluate changes of treatment strength and its impact on prognosis in older patients with ovarian cancer.MethodsWe compared relative dose intensity (RDI) as a representative of treatment strength, prognosis, and other features between older (≥65 years) and younger patients (<65 years) retrospectively. Seventy‐seven older patients of 301 who received dose‐dense‐paclitaxel‐carboplatin (dTC) and 93 older patients of 304 who received conventional‐paclitaxel‐carboplatin (cTC) from the Japanese Gynecologic Oncology Group (JGOG) 3016 clinical trial were analyzed.ResultsThe RDI of older patients was lower than that of younger patients in cTC (87.4% vs. 90.8%, p = 0.009) but not in dTC (79.0% vs. 81.2%, p = 0.205). In both regimens, older patients had worse overall survival than younger patients: hazard ratio [HR] = 1.80; 95% confidence interval [CI]: 1.25–2.59; p = 0.001 for dTC, and HR = 1.59; 95% CI: 1.15–2.19; p = 0.04 for cTC. However, the RDI was not determined as a prognostic factor statistically. The prognostic factors identified by multivariate analysis for both regimens were clinical stage and residual disease; for dTC were age, performance status, and serum albumin; and for cTC was white blood cell count. There was no difference in neutropenia observed between age groups in either regimen.ConclusionsThe RDI of older patients varies according to the administered schedule and is not always lower than that of younger patients. Older patients with comparable treatment strength to younger patients in the dTC group did not accomplish the same level of prognosis as younger patients. Other biologic factors attributable to aging may affect prognosis.

Computed tomography, magnetic resonance imaging, and positron emission tomography/computed tomography findings for the diagnosis of malignant struma ovarii: A case report

AbstractMalignant struma ovarii (MSO) is an extremely rare disease arising from struma ovarii. Preoperative diagnosis is still challenging due to the lack of criteria for imaging findings. Herein, we report a case of MSO with suggestive imaging findings for a 50‐year‐old woman who presented with a pelvic tumor. The tumor did not typically show characteristic imaging findings of struma ovarii; however, the findings implied colloids of thyroid tissue within solid components on the magnetic resonance imaging (MRI) and computed tomography. Additionally, the solid components showed hyperintensity on diffusion‐weighted image and hypointensity on apparent diffusion coefficient maps. Total abdominal hysterectomy, bilateral salpingo‐oophorectomy, and omentectomy were performed. Histopathological examination revealed MSO of the right ovary, pT1aNXM0. The distribution of papillary thyroid carcinoma tissue corresponded to restricted diffusion area on MRI. In conclusion, the coexistence of imaging findings suggesting thyroid tissue and restricted diffusion in the solid component on MRI could indicate MSO.

Sexual quality of life between healthy women and women with gynecological cancer: Results of a hospital‐based case–control study in Türkiye

AbstractBackgroundGynecological cancers among women were both chronic and vitally health problems. The increasing prevalence of women with surviving gynecological cancers and the receiving treatments of cancer negatively affected the sexual quality of life.AimThe study was conducted to determine the sexual quality of life of healthy women and women with gynecological cancer and to determine the predictors of sexual quality of life in women with gynecological cancer.MethodsThe research is a hospital‐based case–control study was conducted. The study was carried out with 65 patients with histologically confirmed gynecological cancer were compared with 75 controls, who were admitted to the different departments of the same hospital in the Izmir, in western Türkiye.ResultsThe Sexual Quality of Life Questionnaire score (SQOL) of cases was 60.12 ± 9.01 and controls was 78.92 ± 7.08. SQOL scores of cases were significantly lower than controls (p < 0.05). Multiple linear regression analysis results showed that age (B = −0.295, p = 0.072), working (B = 4.981, p = 0.016), smoking (B = −4.590, p = 0.035), diagnosed with cervical cancer (B = −4.214, p = 0.045), and receiving chemotherapy (B = −4.722, p = 0.028) were associated with sexual quality of life in women with gynecological cancer (p < 0.05, R2: 0.40).ConclusionWomen with gynecological cancer had lower quality of sex life compared with healthy women. Gynecological cancers negatively affect women's sexual quality of life. Health professionals (especially nurses) should be aware of the potential problems that women with gynecological cancer may experience with their sexual lives. They should develop coping strategies and offer solutions for the problems experienced by women with gynecological cancer.

Factors associated with human papillomavirus persistence after loop electrosurgical excision procedure in patients with cervical squamous intraepithelial lesion

AbstractAimTo seek the high‐risk factors of human papillomavirus (HPV) persistence and residual lesion or recurrence after loop electrosurgical excision procedure (LEEP) focus on the predictive value of intraoperative human papilloma virus (IOP‐HPV) testing.MethodsIntraoperative endocervical sample was obtained with a cytobrush from the remained cervix of 292 patients immediately after LEEP. HPV Genotyping was performed using a polymerase chain reaction technique. All patients followed by HPV genotyping and cytology every 3–6 months. The IOP‐HPV testing results and possible risk factors such as age, cytology grade, menopause status, margin involvement, preoperative HPV status, and cervical lesion grade were assessed in predicting persistence of HPV and residual lesion or recurrence after surgery.ResultsThere were 61 (20.9%) patients presented persistent HPV infection. Multivariate analyses showed that IOP‐HPV positive, post‐menopause and preoperative HPV multiplex infection was strongly associated with HPV persistence after LEEP, IOP‐HPV positive and post‐menopause was also associated with residua or recurrent disease after LEEP.ConclusionsIOP‐HPV positive, post‐menopause, and preoperative HPV multiplex infection are independent predictors of HPV persistence in patients with cervical squamous intraepithelial lesion treated by LEEP. IOP‐HPV test is a new approach that may potentially allow for early identification of patients at high risk of HPV persistence and residua or recurrent disease after LEEP, thereby possibly facilitate an attenuated follow‐up schedule for negative patients those at low risk of persistent HPV infection.

Assessment of the differences in oncologic outcomes between patients with high‐grade serous ovarian carcinoma and uterine serous carcinoma

AbstractAimTo evaluate whether the recurrence rates, recurrence patterns, and survival outcomes differed according to the primary site of the tumor in patients with high‐grade serous ovarian carcinoma (HGSOC) and uterine serous carcinoma (USC).MethodsThe population of this multicenter retrospective study consisted of patients who had USC or HGSOC. Progression‐free survival (PFS) and disease‐specific survival (DSS) estimates were determined using the Kaplan–Meier method. Survival curves were compared using the log‐rank test.ResultsThe study cohort consisted of 247 patients with HGSOC and 34 with USC. Recurrence developed in 118 (51.1%) in the HGSOC group and 14 (42.4%) in the USC group (p = 0.352). The median time to recurrence was 23.5 (range, 4–144) and 17 (range, 4–43) months in the HGSOC and USC groups, respectively (p = 0.055). The 3‐year PFS was 52% in the HGSOC group and 47% in the USC group (p = 0.450). Additionally, 3‐year DSS was 92% and 82% in the HGSOC and USC groups, respectively (p = 0.060).ConclusionsHGSOC and USC are aggressive tumors with high recurrence and mortality rates in advanced stages. These two carcinomas, which are similar in molecular features and clinical management, may also have similar recurrence patterns, disease failure, and survival rates.

A rare case of signet ring cell carcinoma with diffuse cutaneous systemic sclerosis: A case report

AbstractSystemic sclerosis, an autoimmune disease characterized by fibrosis and vasculopathy of the skin and other multiple organs has been associated with an increased risk of malignancy. We present the case of a 74‐year‐old woman who had diffused cutaneous systemic sclerosis and uterine cervical cancer. The patient was initially diagnosed with stage IIB squamous cell carcinoma and concurrent chemoradiotherapy was planned. However, cisplatin could not be administered due to acute renal failure, so the patient was treated solely with radiotherapy. However, complications of systemic sclerosis progressed rapidly, and the patient died 63 days later from pulmonary edema. An autopsy later revealed that uterine cervix had primary signet ring cell carcinoma. We suspected that this patient had a combination of signet ring cell carcinoma and squamous cell carcinoma, with squamous cell carcinoma disappearing after radiotherapy. This case highlighted the importance of systemic management for cancers associated with systemic sclerosis.

Role of systematic pelvic and para‐aortic lymphadenectomy in delayed debulking surgery after six neoadjuvant chemotherapy cycles for high‐grade serous ovarian carcinoma

AbstractIntroductionWe analyzed the role of systematic pelvic and para‐aortic lymphadenectomy in delayed debulking surgery after six neoadjuvant chemotherapy (NACT) cycles for advanced high‐grade serous ovarian carcinoma.Materials and MethodsWe retrospectively reviewed patients with advanced ovarian carcinoma who underwent NACT with carboplatin‐paclitaxel between 2008 and 2016. Patients were included only if they had FIGO IIIC‐IVB high‐grade serous carcinoma with clinically negative lymph nodes after six NACT cycles (carboplatin‐paclitaxel) and underwent complete or near complete cytoreduction. Patients with partial lymphadenectomy or bulky nodes were excluded. Patients who underwent systematic pelvic and aortic lymphadenectomy and those who did not undergo lymph node dissection were compared. Progression‐free and overall survivals were analyzed using the Kaplan–Meier method.ResultsTotally, 132 patients with FIGO IIIC‐IVB epithelial ovarian carcinoma were surgically treated after NACT. Sixty patients were included (39 and 21 in the lymphadenectomy and nonlymphadenectomy group, respectively); 40% had suspicious lymph nodes before NACT. Patient characteristics, blood transfusion numbers, and complication incidence were similar between the groups. In the lymphadenectomy group, 12 patients (30.8%) had histologically positive lymph nodes and the surgical time was longer (229 vs. 164 min). The median overall survival in the lymphadenectomy and nonlymphadenectomy groups, respectively, was 56.7 (95% CI 43.4–70.1) and 61.2 (21.4–101.0) months (p = 0.934); the corresponding disease‐free survival was 8.1 (6.2–10.1) and 8.3 (5.1–11.6) months (p = 0.878). Six patients exclusively presented with lymph node recurrence.ConclusionsSystematic lymphadenectomy after six NACT cycles may have no influence on survival.

Colposcopic scoring indexes in the evaluation of cervical lesions with the cytological result of atypical squamous cells, cannot exclude high‐grade lesion

AbstractAimColposcopic indexes including Reid index and Swede score were developed to make the colposcopy more objective. The aim of our study was to evaluate the significance of colposcopic indexes in the evaluation of ASC‐H cervical lesions.MethodsWe carried out a cross‐sectional study in the Clinic of Obstetrics and Gynecology between January 2013 and December 2018. The study included 535 women, from which 66 women had a cytological result ASC‐H. Scoring of all colposcopic findings was assessed according to Reid modified index and Swede score and a composite score was determined. Frequency distributions were compared using χ2/Fisher exact test. Spearman rank correlation coefficient was computed between RCI and Swede score.ResultsSensitivity, specificity, positive and negative predictive value and positive likelihood ratio of modified Reid colposcopic index at a cutoff of ≥4 for the detection of HSIL+ lesions were: 86.11% (95% CI: 70.5–95.3), 83.33% (95% CI: 65.3–94.4), 86.11% (95% CI: 69.7–94.8), 83.33% (95% CI: 64.5–93.7) and 5.17 (95% CI: 2.3–11.6). Swede score with the cutoff value ≥5 showed comparable results to modified Reid index with the increased sensitivity: 94.44% (95% CI: 81.3–99.3).ConclusionASC‐H category represents the trickiest cytological diagnosis as it is underlined with the high risk of severe cervical dysplasia. Evaluating the cervical lesion by the use of colposcopic indices helps the gynecologist to objectively evaluate all the pathologies of uterine cervix. Swede score with the cutoff value 8 also enables a ‘see and treat’ option in management of atypical squamous cells, cannot exclude high‐grade lesions.

Smartphone‐assisted tele‐gynepathology: A pilot study

AbstractIntroductionTraditional telepathology techniques like whole slide imaging require expensive equipment and are currently out of reach of the developing countries. However, the improvements in smartphone camera resolution and availability of faster internet have made smartphone‐assisted telepathology possible.MethodsA total of 186 cases pertaining to gynecologic pathology reported by single consultant (NT) were retrieved from the records of the histopathology department. A trained histopathologist then photographed representative areas of each case by using the smartphone camera. After a wash off period of 6 months, the images along with the clinical details were sent by Whatsapp Messenger to the same reporting pathologist. The reporting pathologist replied with the diagnosis of each case by using Whatsapp.ResultsThe smartphone diagnosis was concordant in 179/186 (96.2%) cases. The intraobserver concordance rates varied with the organ involved – it was highest for endometrial and myometrial pathology (123/126, 97.6%) lowest for ovarian lesions (08/10, 80%). For cervical pathology, it was 97.2% (35/36) and for fallopian tube pathology it was 92.9% (13/14).ConclusionAlthough the initial results of this pilot study are encouraging, there is a long way to go before smartphone‐assisted telepathology can be put to routine use for the second opinion. More experience of the pathologists with this technique and faster internet and better smartphone cameras will further improve the concordance of smartphone‐assisted telepathology diagnosis with conventional microscopy diagnosis.

Evaluation of American College of Radiology Ovarian‐Adnexal Reporting and Data System ultrasound to predict malignancy risk in adnexal lesions

AbstractAimsTo validate the diagnostic performance of Ovarian‐Adnexal Reporting and Data System (O‐RADS) ultrasound for preoperative adnexal lesions in an external center. The secondary aim was to evaluate the performance of a strategy test including O‐RADS ultrasound evaluation and subjective assessment of higher malignant risk lesions.MethodsOne hundred thirty patients with 158 ovarian‐adnexal lesions were enrolled in the study. Each lesion was assigned an O‐RADS score after real‐time ultrasound examination by one experienced radiologist. A second subjective assessment by an expert was performed for O‐RADS 4 and O‐RADS 5 lesions. The histopathological diagnosis was used as the reference standard.ResultsA total of 126 benign and 32 malignant adnexal masses were included in the study. The area under the receiver operating characteristic curve of O‐RADS ultrasound was 0.950, with a cutoff value > O‐RADS 3. The sensitivity, specificity, and negative and positive predictive values were 100% (95% confidence interval [CI], 0.867–1), 83.3% (95% CI, 0.754–0.892), 60.4% (95% CI, 0.460–0.732), and 100% (95% CI, 0.956–1), respectively. For the strategy test, the sensitivity, specificity, negative and positive predictive values were 100% (95% CI, 0.867–1), 92.1% (95% CI, 0.855–0.959), 76.2% (95% CI, 0.602–0.874), and 100% (95% CI, 0.960–1), respectively. In comparison with O‐RADS ultrasound, the specificity and negative predictive value of the strategy test were slightly higher (p < 0.05).ConclusionsGood diagnostic performance of the O‐RADS ultrasound in adnexal lesions can be achieved by experienced radiologists in clinical practice. A second subjective assessment of sonographic findings can be applied to O‐RADS 4 and 5 lesions.

Giving birth after fertility‐sparing treatment for primary leiomyosarcoma of the fallopian tube

AbstractPrimary leiomyosarcoma of the fallopian tube (PLFT) is an extremely rare gynecological malignancy that has only been described in case reports. Fertility‐sparing treatment for PLFT has not been reported previously. A 24‐year‐old nulligravida woman was diagnosed with stage IC1 PLFT in the right fallopian tube after experiencing right lower quadrant pain for 2 weeks. She underwent laparoscopic right salpingectomy to preserve fertility followed by adjuvant chemotherapy with gemcitabine/docetaxel. She subsequently became pregnant spontaneously, delivering a term baby 27 months after treatment. This appears to be the only report of the use of fertility‐preserving treatment for PLFT. The success of the treatment provides valuable information on the preservation of fertility in young women with PLFT.

The influence of radical trachelectomy on endometrial thickness in in vitro fertilization‐embryo transfer

AbstractAimBoth morbidity and mortality rates of cervical cancer are increasing, especially in reproductive‐aged women. Radical trachelectomy (RT) is an effective fertility‐preserving surgery for early‐stage cervical cancer. This study aimed to determine the influence of RT on endometrial thickness during in vitro fertilization‐embryo transfer (IVF‐ET).MethodsForty‐four patients had undergone RT, and 23 women undergoing IVF‐ET treatment (105 ET cycles) were included. Endometrial thickness during hormone replacement therapy (HRT) was retrospectively evaluated and compared between patients with and without RT.ResultsEleven patients (50 ET cycles) in the RT group and 12 (52 ET cycles) in the control group were investigated. Compared with the control group, higher ET cancellation rates were observed in patients in the RT group (1 of 52 cycles [control group] vs. 8 of 50 cycles [RT group], p < 0.01). Endometrial thinning was not affected by patient age at first IVF‐ET treatment, history of artificial abortion, preservation of uterine arteries during RT, or postoperative chemotherapy (p = 0.27, 1, 1, and 1, respectively).ConclusionsOur data revealed that RT influenced endometrial thickness in IVF‐ET. This was not affected by the background of the patients or perioperative management in this study. We could not reveal the underlying mechanism, but it is postulated that the transient postoperative uterine blood flow status and postoperative infections may have some effect on the endometrium. To resolve these issues, accumulation of evidences are required. We recommend informing patients about the impact of RT on IVF‐ET before starting assisted reproductive technology (ART).

An update of oncologic and obstetric outcomes of radical trachelectomy for early‐stage cervical cancer: The need for further minimally invasive treatment

AbstractAimsTo investigate the oncologic and obstetric outcomes of radical trachelectomy (RT) in patients with early‐stage cervical cancer and to evaluate the potential role of fertility‐preserving treatments in improving pregnancy outcomes while oncologic status is stable.MethodsIn this single‐institution study, we analyzed the oncologic and obstetric outcomes of 67 patients with early‐stage cervical cancer who underwent RT at Nagoya University Hospital.ResultsThe cancer recurrence rate (6.0%) and the mortality rate (1.5%) were comparable with those of previous studies. Of the 46 patients who attempted to conceive after RT, 19 (41.3%) became pregnant, and 16 gave birth. Of these 37.5% delivered at term, and delivery at less than 28 weeks of gestation occurred in 31.3% of pregnancies.ConclusionsRT is a viable treatment option for selected patients with early‐stage cervical cancer. However, the use of less invasive techniques, such as conization/simple trachelectomy and pelvic lymph node dissection, may improve pregnancy outcomes while oncologic status is stable.

Malignant peripheral nerve sheath tumor of the cervix in an adolescent with neurofibromatosis type 1: A case report and review of literature

AbstractMalignant peripheral nerve sheath tumors (MPNSTs) of the cervix are rare, particularly in patients with neurofibromatosis type 1 (NF1). This report describes a cervical MPNST in an 18‐year‐old patient with no history of sexual activity, abnormal vaginal discharge, and prolonged menstruation. She had more than six café‐au‐lait spots on her body since birth and was diagnosed with NF1 at 2 years of age. Positron emission tomography‐computed tomography revealed a large pelvic mass and lung and bone metastases. Biopsy confirmed MPNST. Immunohistochemical staining showed diffuse positivity for CD10, approximately 30% positivity for cyclin D1, partial positivity for α‐SMA, desmin, and MyoD1, and negativity for myogenin, S‐100, and SOX‐10. A cancer gene panel identified several genetic abnormalities, but none were actionable mutations. Despite systemic chemotherapy, the tumor progressed rapidly, and the patient died 8 weeks post‐admission. Early diagnosis of MPNST is crucial. In patients with NF1, even mild symptoms can indicate MPNST.

Telomerase reverse transcriptase gene polymorphisms and cervical cancer susceptibility in high‐risk human papillomavirus‐infected women

AbstractObjectiveTo investigate the relationship between Human telomerase reverse transcriptase (hTERT) gene polymorphisms and the susceptibility and clinicopathological parameters of cervical cancer in women infected with high‐risk human papillomavirus (HR‐HPV).MethodA total of 380 patients with HPV‐infected cervical cancer who were admitted to the Jilin province Maternal and Child Health Care Hospital (Jilin province Obstetrics Quality Control Center) from July 2019 to July 2023 were selected as case group, and 408 women with negative HPV results in the cervical cancer screening results of the physical examination in the same hospital were selected as the control group. Restriction fragment length polymorphisms polymerase chain reaction was used to detect the polymorphisms of hTERT, and its relationship with the susceptibility to high‐risk HPV infection and clinicopathological parameters in patients with cervical cancer was analysed.ResultsIndividuals carrying the GA and AA genotypes of rs2736122 were significantly associated with an increased risk of cervical cancer when compared with the GG genotype and the adjusted ORs were 0.53 (0.37–0.79) for the AA genotype and 0.73 (0.59–0.88) for the A allele genotype. Besides, GG genotype or G allele of rs2853677 presented a significant influence on cervical cancer, with ORs of 0.59 (0.41–0.86) and 10.77 (0.63–0.94), respectively, when compared with the AA genotype. And rs2853677 have statistically significant difference in tumour diameter and degree of differentiation subgroup(p < 0.05).ConclusionThe results of this study indicate that the hTERT gene rs2736122AA and rs2853677 GG genotypes can increase the susceptibility of high‐risk HPV infection in cervical cancer patients. And rs2853677 is related to tumours above 4 cm and highly differentiated tumours. But both have nothing to do with the patient's chemotherapy sensitivity.

Are HPV‐negative lesions concerned for the introduction of primary HPV testing for cervical cancer screening in Japan?

AbstractAimIn Japan, primary human papilloma virus (HPV) testing has not been introduced for cervical cancer screening due to concerns that HPV‐negative lesions may be missed and a lack of Japanese data. The purpose of this study was to evaluate the validity of primary HPV testing in Japan by analyzing cervical intraepithelial neoplasia 2 (CIN2) or more/high‐risk HPV− (CIN2+/hrHPV−) cases in cervical cancer screening.MethodsData from 35 525 cervical cancer screenings with HPV testing and cervical cytology from 2011 to 2019 in Saga City, Japan, were reviewed. The cases with low‐grade squamous intraepithelial lesion (LSIL+)/hrHPV− were analyzed in detail.ResultsThe results of the 35 525 examinees were as follows: 31 123 were negative for intraepithelial lesion or malignancy (NILM)/hrHPV–, 2612 were NILM/hrHPV+, 262 were atypical squamous cells of undetermined significance (ASC‐US)/hrHPV–, 213 were ASC‐US/hrHPV+, 291 were LSIL+/hrHPV−, and 1024 were LSIL+/hrHPV+. Of the 256 LSIL+/hrHPV− examinees for whom histology was available, CIN2+ were CIN2 9.4% (24/256), CIN3 3.9% (10/256), cervical adenocarcinoma 0.4% (1/256), uterine corpus cancer 1.2% (3/256), and uterine sarcoma 0.4% (1/256). Overall, the rate of LSIL+/hrHPV− was 0.82% (291/35.525), 0.1% (36/35525) of which were cervical lesions with CIN2+. Only one cervical adenocarcinoma was detected, but gastric‐type adenocarcinoma was not included.ConclusionHPV‐negative CIN2+ or cervical adenocarcinoma is not a concern for the introduction of primary HPV screening in Japan. Primary HPV testing in cervical cancer screening is considered a feasible method that can be used in Japan, although an algorithm suitable for Japan and a national‐level management system need to be established.

Paclitaxel‐carboplatin plus bevacizumab therapy for advanced neuroendocrine carcinoma of the uterine cervix: A retrospective case series

AbstractAimThere is no conclusive data on the prognosis of patients who receive paclitaxel‐carboplatin (TC) plus bevacizumab therapy for advanced neuroendocrine carcinoma (NEC) of the uterine cervix, a rare histological subtype of cervical cancer. Thus, the aim of this study was to determine the efficacy of TC chemotherapy plus bevacizumab and bevacizumab single maintenance therapy for advanced NEC of the cervix.MethodsThis was a retrospective review of patients who received TC plus bevacizumab therapy for metastatic, recurrent, or persistent NEC of the cervix at seven institutions between 2015 and 2020. Relevant data were extracted from the patients' medical records and analyzed.ResultsSeven patients, including six with small‐cell NEC and one with large‐cell NEC, were included for analysis. Three patients received bevacizumab single maintenance therapy following TC plus bevacizumab therapy, whereas four patients did not receive bevacizumab single maintenance therapy. The median overall survival and progression‐free survival of the patients who received bevacizumab single maintenance therapy were longer than those of the patients who did not receive the therapy (34 months vs. 10.5 months and 19 months vs. 5 months, respectively). However, the patients who received bevacizumab single maintenance therapy had received cisplatin‐based chemotherapy previously.ConclusionsOn the premise that cisplatin‐based chemotherapy is administered as the first‐line treatment for advanced NEC of the cervix, bevacizumab single maintenance therapy following TC plus bevacizumab may be considered the second‐ or third‐line treatment. However, the risk of adverse events, such as intestinal perforation, should be discussed with patients.

Laparoscopic versus open radical hysterectomy in FIGO 2018 early‐stage cervical adenocarcinoma: Long‐term survival outcomes after propensity score matching

AbstractObjectiveTo compare the long‐term survival outcomes of laparoscopic radical hysterectomy (LRH) and open radical hysterectomy (ORH) in International Federation of Gynecology and Obstetrics (FIGO) 2018 early‐stage cervical adenocarcinoma.MethodsBased on the clinical diagnosis and treatment for cervical cancer in mainland China (Four C) database, the medical records of 1098 patients with FIGO 2018 early‐stage cervical adenocarcinoma were retrospectively reviewed. Long‐term and short‐term survival outcomes of the two groups were compared using a multivariate Cox regression model and the log‐rank method in the whole study population and after propensity score matching.ResultsThere was no difference in disease‐free survival (hazard ratio [HR] 0.921, 95% confidence interval [CI]: 0.532–1.595, p = 0.770) and overall survival (HR 1.168, 95% CI: 0.526–2.592, p = 0.702) between LRH (n = 468) and ORH (n = 468) in the risk‐adjusted analysis. LRH resulted in significantly lower estimated blood loss (342.7 vs. 157.5 mL, p < 0.001) and shorter postoperative anal exhaust time (2.8 vs. 2.5 days, p < 0.001) in risk‐adjusted analysis. The overall rates of intraoperative complications (2.4% vs. 4.3%, p = 0.100) and postoperative complications (7.5% vs. 6.2%, p = 0.437) showed no significant difference between the two groups. However, the LRH group had a significantly higher incidence of ureter injury (0.4% vs. 2.4%, p = 0.012) and great vessel injury (0.0% vs. 0.9%, p = 0.045) compared to the other group. No statistical variation in the site of recurrence was observed between the two groups (p = 0.613).ConclusionsLRH has comparable survival outcomes with ORH and was associated with earlier recovery in FIGO 2018 early‐stage adenocarcinoma of the uterine cervix. However, the LRH group had higher risk of ureter injury and great vessel injury.

Investigation of human papilloma virus frequency in pregnant women

AbstractObjectiveThe aim of this study was to determine the frequency of human papillomavirus (HPV), HPV types, and the association with age, pregnancy, and childbirth in pregnant women.MethodFour hundred and forty‐eight pregnant women who visited our clinic were enrolled in the study. Polymerase chain reaction was used to determine HPV DNA and typing by cervical smear in the initial applications of patients with detailed history. Statistical Package for the Social Sciences (SPSS) 13.0 was used to analyze the data.ResultsHPV DNA was positive in 26 (5.8%) of 448 patients who participated in the study. High‐risk HPV types were detected in 77% of HPV‐positive cases and low‐risk HPV types in 23% of cases. Only one HPV type was detected in 13 patients (50%), while multiple HPV types were detected in 13 patients (50%) of the HPV‐positive cases. A significant negative association was found between gravidity and positivity of HPV DNA. HPV is more common in women with lower parity and gravidity.ConclusionStudies conducted in different populations in different regions of Turkey have shown that the incidence of HPV in women ranges from 2.2% to 26%. In our study, the incidence of HPV DNA in pregnant women was 5.8%. It was found that there was an inverse relationship between parity and HPV DNA positivity. The HPV DNA positivity decreased with the number of births.

Knowledge levels and community guidance of doctors working in family health centers on HPV screening and HPV vaccination

AbstractAimOur aim is to evaluate the level of knowledge, compliance with the screening program, and tendency to inform patients of the doctors working in FHCs where HPV testing is performed within the scope of the cervical cancer screening program in our country.MethodsThis cross‐sectional study was performed between June and September 2022 with 113 family physicians working in different FHCs in different provinces in Turkey. Questionnaires prepared by the researchers were delivered to family physicians via online platforms.ResultsWhen the different age groups were evaluated, in two of the 24 knowledge‐level questions (How many types of HPV are there? Can HPV infect men?) the rate of correct answers for participants under the age of 35 years was statistically significantly higher (p = 0.007; p = 0.032). With regard to professional experience, the group with fewer than 10 years of experience gave a statistically significant correct answer to two questions (How many types of HPV are there? Can HPV infect men?; p = 0.008; p = 0.037). It was observed that 107 (94.7%) of the 113 family physicians who participated in the survey recommended that their patients use condoms during intercourse, 110 (97.3%) recommended cervical cancer screening tests to patients who applied for another reason, 105 (92.9%) recommended the HPV vaccine to patients and their relatives and 60 (53.1%) recommended the HPV vaccine to patients who applied for another reason.ConclusionsThe success of HPV vaccination programs is directly related to the beliefs of health personnel and their recommendations to the general population.

Reduced 2,4‐dienoyl‐CoA reductase 1 is served as an unfavorable biomarker and is related to immune infiltration in cervical cancer

AbstractBackgroundWorldwide, cervical cancer (CC) remains the most prevalent malignancy of the female reproductive system, posing a threat to women's life and health, and increasing the medical and economic burden on society. Therefore, the search for tumor biomarkers for CC remains an important research direction. Immunotherapy has significantly improved patient outcomes, and genes related to tumor immune infiltration have been clinically relevant and highly reproducible biomarkers that affect the prognosis and response to treatment of CC. 2,4‐dienoyl‐CoA reductase 1 (DECR1) was considered to be an oncogene in a previous study, but relationship between DECR1 and immune infiltration was not mentioned. Our study aimed to reveal the clinical value of DECR1 in CC and to investigate its relationship with immune infiltration.MethodsHuman Protein Atlas was used to identify the localization of DECR1. The Ualcan database, TCGA, and IHC were used to assess the prognostic value of DECR1. GSEA was used to assess the possible signaling pathways of DECR1 in CC. The TIMER database was applied to reveal the relevance between DECR1 and immune infiltration. GEPIA was conducted to detect the co‐relationship among DECR1, immune markers, and typical molecules of apoptosis.ResultsDECR1 was mainly distributed in the cytoplasm and overlapped with the endoplasmic reticulum. DECR1 was downregulated in CC compared to adjacent tissue. Survival analysis showed that patients with lower expression of DECR1 have a worse prognosis in CC. GSEA suggested that DECR1 was closely related to apoptosis signaling. TIMER showed that DECR1 was positively correlated with CD8+ T cell and CD4+ T cell but not with B cell in CC.ConclusionDECR1 may be a potential cancer suppressor in CC and may be involved in apoptotic pathways and associated with immune infiltration.

Development and internal validation of a multivariable prediction model for the quality of life of cervical cancer survivors

AbstractPurposeTo elaborate a prediction model for quality of life of cervical cancer survivors.MethodsWe conducted a prospective cohort study on 229 cervical cancer survivors. The quality of life measures included the Functional Assessment Cancer Therapy‐Cervix version 4.0 and the World Health Organization Quality of Life‐brief version self‐administered questionnaires. We imported the data into the statistical software program R and developed a gamma generalized linear model.ResultsOur internally validated predictive model for the Functional Assessment Cancer Therapy‐Cervix total score was composed of the following predictors: pain, appetite, vaginal bleeding/discharge/odor, and WHOQOL‐BREF social relationships domain. The Harrell's concordance index was 0.75.ConclusionsWe developed a solid and internally validated predictive model in cervical cancer survivors based on predictors, such as pain, appetite, vaginal bleeding/odor/discharge, and WHOQOL‐BREF social relationships subscale score that contribute significantly to quality of life as targets for potential intervention.

The significance of nonsurgical therapies for cervical infection of high‐risk human papilloma virus: A systematic review and meta‐analysis

AbstractObjectiveTo assess whether nonsurgical therapies were related with clearance of cervical infection of high‐risk human papilloma virus (hr‐HPV) or regression of mild abnormal cytology related with hr‐HPV.MethodsUntil March 2023, we identified a total of 10 424 women with cervical infection of hr‐HPV and 1966 women with mild abnormal cytology related with hr‐HPV from 44 studies that met the inclusion criteria.ResultsAfter systematically retrieving literature, we identified 2317 citations and 44 randomized controlled studies (RCT) were enrolled. Cumulative results suggested women with cervical infection of hr‐HPV might benefit from nonsurgical therapies. Both the clearance of hr‐HPV (OR: 3.83, I2 = 99%, p < 0.00001) and regression of mild abnormal cytology related with hr‐HPV (OR: 3.12, I2 = 63%, p < 0.00001) were significantly higher than control group. Subgroup analysis stratified by systematic therapy, topical therapy, traditional Chinese medicines (TCMs), and presistent hr‐HPV got consistent results. There was substantial heterogeneity between trials (I2 = 87% for clearance of hr‐HPV and 63% for regression of cytology), sensitivity analysis was performed by excluding single study one by one, and found the cumulative results were stable and dependable. Both the funnel plots for clearance of hr‐HPV and regression of abnormal cytology were asymmetrical, significant publication bias might exist.ConclusionNonsurgical therapies might benefit women who had a cervical infection of hr‐HPV with/without mild abnormal cytology related with hr‐HPV. Both the clearance of hr‐HPV and regression of abnormal cytology were significantly higher than control group. More studies with less heterogeneity were needed urgently to draw concrete conclusion.

Risk factors for recurrence of cervical intraepithelial neoplasia after loop electrosurgical excisional procedure in patients with positive margins

AbstractAimLoop electrosurgical excisional procedure (LEEP) is a major treatment method for cervical precancerous lesions. However, recurrence rates were estimated to be 15%, and the risk is increased if a surgical margin is involved by dysplastic cells. This study aimed to identify the risk factors for recurrence of cervical precancerous lesions in patients with positive margins.MethodsWe retrospectively reviewed medical records of patients who underwent LEEP between 2012 and 2014 and had a positive surgical margin. Clinicopathologic factors were collected, including age, parity, menopausal status, smoking, human papilloma virus infection, results of cytology/biopsy/LEEP, and specimen size and volume.ResultsA total of 117 patients with positive margins were included, and 26 (22.2%) patients had recurrence. According to a multivariate analysis, the recurrence rates were significantly higher in parous women (adjusted hazard ratio [HR], 2.92; 95% confidence interval [CI], 1.00–8.49), but positive margins at the exocervix (adjusted HR, 0.39; 95% CI, 0.17–0.91) and volume ≥4000 mm3 (adjusted HR, 0.36; 95% CI, 0.16–0.82) showed negative correlation.ConclusionsThe risk of recurrence for cervical precancerous lesions increased in patients with a history of previous delivery, positive margin at the endocervix, and specimen volume of LEEP <4000 mm3. These results could help gynecologists determine optimal treatment options for patients with positive margins.

Cytomorphology and immunocytochemical features of ovarian granulosa cell tumors in ascites or peritoneal washings: A retrospective review

AbstractAimTo summarize the cytomorphology and immunocytochemistry features of OGCT in ascites or peritoneal washings.MethodsAll cases of histology sections, cytology smears, cell block slides and immunohistochemical staining were reviewed. A panel of immunohistochemistry antibodies consisting of Inhibin, Calretinin, BerEP4 and MC was performed for diagnosis and differential diagnosis.ResultsSeven positive cases (21.2%) in ascites and peritoneal washings were identified in 33 patients with OGCT, which is higher than early studies with positive rate of 7.4%. Clinicopathologic features including tumor size and the incidence of endometrial atypical hyperplasia or carcinoma (EAH/EC) displayed no statistical difference between groups with positive and negative cytology. Immunocytochemical results usually showed typical staining pattern with α‐inhibin, calretinin positive and BerEP4, MC negative. Features of granulosa cells, including nuclear hyperplasia and overlapping, can be observed in all seven positive cases. Nuclear grooves or small conspicuous nucleoli were occasionally observed in the smear. However, features of cell clusters mimicking Call‐Exner bodies, cytoplasmic vacuoles or single cell necrosis were not found on smear. Call‐Exner bodies and mitosis can only be found on cell blocks. All cases of follow‐up information were available and three cases displayed progression and there was a statistical difference between groups with positive and negative cytology.ConclusionOGCT with positive cytology in ascites and peritoneal washings tend to have a larger tumor size and higher rates of disease progression. A panel of complementary biomarkers can greatly increase the detection rate and help in differential diagnosis in ascites or peritoneal washings of OGCT.

Diagnostic performance of CA125, HE4, ROMA, and CPH‐I in identifying primary ovarian cancer

AbstractAimsTo evaluate the ability of carbohydrate antigen 125 (CA125), human epididymis protein 4 (HE4), risk of ovarian malignancy algorithm (ROMA), and Copenhagen Index (CPH‐I) to identify primary ovarian cancer (OC) from borderline and benign ovarian tumors (OTs) and explore ideal cutoff points.MethodsA total of 684 OTs containing 276 OC patients, 116 ovarian borderline OTs and 292 benign OTs patients who underwent surgery in our hospital were included. We retrospectively searched the results of CA125 and HE4 before patients' surgery from the hospital's electronic medical records system. ROMA and CPH‐I were calculated according to their menopausal status and age, respectively. Diagnostic performance of these four were assessed by drawing receiver operating characteristic (ROC) curves.ResultsCA125, HE4, ROMA, and CPH‐I were all significantly higher in OC women compared with borderline OTs (p < 0.001), followed by benign OTs (p < 0.001). Area under the curves (AUCs) for distinguishing OC were 0.850 (0.818–0.882), 0.891 (0.865–0.916), 0.910 (0.888–0.933) and 0.906 (0.882–0.930), respectively, and the corresponding ideal cutoff values for CA125, HE4, ROMA, and CPH‐I were 132.5, 68.6, 23.8, and 6.4, respectively. The difference between ROMA and CPH‐I was not significant (p = 0.97), but both were higher than CA125 and HE4 (p < 0.05). HE4 showed a significantly higher AUC than CA125 (p < 0.05). For postmenopausal women, CA125 performed equivalently to ROMA (p = 0.73) and CPH‐I (p = 0.91).ConclusionsIn identifying patients with OC, ROMA and CPH‐I outperformed single tumor marker. The diagnostic performance of HE4 was significantly higher than that of CA125. CA125 was more suitable for postmenopausal women.

A comparison of the associations of Reid Colposcopic Index and Swede Score with cervical histology

AbstractAimCervical cancer, the fourth most common cancer in women, is preventable. Colposcopy and colposcopic scoring systems are helpful tools to guide the treatment of precancerous lesions. This study was done to compare the association between Reid colposcopic index (RCI) and Swede score.MethodsThis prospective study enrolled 159 subjects aged 18 years or over with abnormal pap smears or high‐risk HPV (types 16 and/or 18). All women underwent colposcopies, and the findings were classified by RCI and Swede score. Biopsies were done in all cases. The performance of both scores was evaluated.ResultsA total of 43 (27.0%) high‐grade lesions were detected. AUC of ROC of both tests showed excellent performance with 0.906 for RCI and 0.902 for Swede score. The correlation coefficient was 0.986. At a cutoff of 5, RCI had a sensitivity, specificity, positive predictive value, and negative predictive value for detected CIN2+ lesions of 83.7%, 89.7%, 75.0%, and 93.7%, respectively. At a cutoff of 7 for RCI score, the corresponding figures were 46.5%, 99.1%, 95.2%, and 83.3%. At a cutoff of 5, Swede score had a sensitivity, specificity, positive predictive value, and negative predictive value of 88.4%, 87.1%, 71.7%, and 95.3%. At a cutoff of 9 for Swede score, those values were 14.0%, 99.1%, 85.7%, and 75.7%.ConclusionThere was a good association between RCI and Swede score. Both scoring systems had the good performance. Swede score is effective for practical use and applied in Thailand.

Mesonephric‐like adenocarcinoma of the ovary in an elderly woman: A case report and a review of the literature

AbstractMesonephric‐like adenocarcinoma (MLA) is a rare tumor that occurs in the uterine endometrium and ovary. It morphologically and immunohistochemically resembles cervical mesonephric adenocarcinoma (MA). Here, we present a case of MLA of the ovary along with a literature review. An asymptomatic 84‐year‐old woman presented with a pelvic mass, detected by computerized tomography. Magnetic resonance imaging demonstrated a polycystic mass with a solid component in the left adnexal region. The solid component showed low signal intensity on T2‐weighted imaging and high signal intensity on diffusion‐weighted imaging. We strongly suspected an ovarian malignant tumor; therefore, surgical resection of the uterus and adnexa was performed. Macroscopically, the tumor was predominantly solid with yellowish‐tan cut surface. Microscopically, it showed a tubular pattern with intraluminal colloid‐like material resembling MA. The tumor cells were negative for estrogen receptor, calretinin, and CD10 and positive for PAX8 and TTF‐1. These findings are consistent with those of MLA.

Factors associated with the inconsistent diagnosis between frozen section and permanent pathologic examination in borderline ovarian tumors

AbstractAimThe predictive accuracy of frozen sections for borderline ovarian tumors (BOTs) is suboptimal. The aim of this study was to determine the diagnostic accuracy of BOTs and factors associated with an upgrade to a permanent pathological diagnosis of invasive carcinoma in patients diagnosed with BOTs by frozen section.MethodsWe conducted a retrospective study between 2011 and 2018 at Kaohsiung Chang Gung Memorial Hospital (KCGMH). Two hundred and twenty‐five records of eligible patients with a diagnosis of BOT by frozen section or permanent diagnosis were reviewed. Positive predictive value and the diagnostic accuracy of frozen sections were calculated. Univariate and multivariate analyses were used to determine the clinicopathological factors associated with an upgrade of the diagnosis from a borderline tumor to malignancy.ResultsThe agreement between frozen section and permanent pathological diagnoses was 63.1%, and the positive predictive value was 72.1%. The multivariate analysis revealed that CA‐125 level > 136 U/mL (odds ratio [OR] = 2.96, 95% confidence interval [CI] = 1.3–6.9; p = 0.012), and tumor histologic type (clear cell/endometrioid vs. mucinous; OR:32.8, 95% CI = 6.9–154.8, p < 0.001; clear cell/endometrioid vs. serous: OR 48.1, 95% CI = 8.8–261.8, p < 0.001) were independent risk factors for an upgrade of the permanent diagnosis from a BOT to ovarian carcinoma.ConclusionAn elevated CA‐125 level (over 136 U/mL) and tumor histologic type (clear cell and endometrioid subtypes) were associated with an upgrade in the diagnosis of ovarian tumor from a BOT on frozen section to a permanent diagnosis of malignancy.

Current and future strategies for treatment of ovarian clear cell carcinoma

AbstractOvarian clear cell carcinoma (OCCC) is one of the five histological types of epithelial ovarian cancer (EOC). OCCC comprises 23% of all EOC cases in Japan, whereas the rate of OCCC in North America and Europe is much lower. OCCC is generally categorized as a rare gynecologic malignancy, and there is limited evidence for specific treatment. The clinical basis for treatment of OCCC is mostly based on retrospective studies, many of which were performed in Japan. Until recently, most randomized clinical trials for EOC have included OCCC; therefore, current treatment for OCCC is basically the same as that for other histologic types of EOC. However, the clinical characteristics of OCCC differ from those of high‐grade serous carcinoma, particularly for chemosensitivity, and there is a need to develop new treatment for OCCC. The molecular background of OCCC has unique features: tumors are usually negative for p53 mutations and positive for ARID1A and/or PIK3CA mutations, whereas p53 mutations are common in high‐grade serous or endometrioid carcinomas. These features may help in development of new treatment for OCCC. In this review, we described the current evidence for treatment of OCCC, including surgery, radiotherapy, chemotherapy, molecular targeted therapy and immunotherapy, and we discuss ongoing clinical trials and preclinical studies of new treatment approaches for OCCC.

Reduced levels of actin gamma 1 predict poor prognosis in ovarian cancer patients

AbstractAimTo investigate the expression and function of actin gamma 1 (ACTG1) in ovarian cancer.MethodsWe performed immunohistochemical staining of 176 ovarian cancer tissue samples in a human tissue microarray to detect expression of ACTG1. Staining intensity was examined in relation to clinicopathological parameters. To investigate the prognostic value of ACTG1, ACTG1 mRNA data from 300 ovarian cancer patients in The Cancer Genome Atlas database were examined.ResultsThe immunohistochemical results demonstrated that levels of ACTG1 were reduced in the samples of human ovarian cancer tissue that were examined, and the levels negatively correlated with various clinicopathological parameters. Levels of ACTG1 mRNA also negatively correlated with clinical stage. In Kaplan–Meier survival analysis, higher levels of ACTG1 mRNA were associated with improved overall survival. In multivariate analysis by Cox regression, ACTG1 expression was identified as an independent prognostic marker of favorable overall survival.ConclusionACTG1 may represent a valuable marker for the prognosis of ovarian cancer, and further studies of ACTG1 are warranted.

Management of advanced ovarian cancer in Leicester: The benefits of a paradigm shift in surgical approach

AbstractAimSurgery for advanced ovarian cancer (AOC) has evolved over the past decade to ingeminate the need to offer maximum effort surgery (MES). The aim of this study is to analyze the implementation of a paradigm shift in the surgical management of women with AOC at the University Hospitals of Leicester NHS Trust (UHL) in 2015, until 2020, compared to 2011–2014.MethodsRetrospective cohort study of women with AOC who underwent cytoreductive surgery (CRS) in the UHL. The two groups were: 153 women from January 2011 to December 2014 (group 1), 136 women from January 2015 to January 2020 (group 2).ResultsIn group 1, the 1, 3, and 5 years overall survival rates (OS) were, 90.4%, 33.7%, and 19.3%, compared to 90.2%, 55.4%, and 29.7%, respectively, in group 2 (p = 0.012). Significantly more women had CRS in group 2: 45—Primary debulking surgery (PDS) and 57—interval debulking surgery (IDS) versus 17—PDS & 67—IDS in group 1 (p < 0.001). Surgical complexity score (modified Aletti score) was higher in group 2 compared to group 1 (p = <0.001). No significant difference was noted in the postoperative complications, in group 2, in women who underwent PDS versus IDS, yet PDS was associated with higher OS.ConclusionsMES/CRS in women with AOC significantly improves OS. Our data highlights the importance of a dedicated team to implement this change in cancer centers. Where possible, suitable women with AOC likely to have complete cytoreduction based on preoperative assessment, should be offered PDS.

Circular RNA PVT1 enhances cell proliferation but inhibits apoptosis through sponging microRNA‐149 in epithelial ovarian cancer

AbstractAimThis study aimed to investigate the influence of circular RNA PVT1 (circ‐PVT1) on epithelial ovarian cancer (EOC) cell proliferation and apoptosis, more importantly, to identify the target microRNAs (miRNA) of circ‐PVT1 in EOC.MethodsCirc‐PVT1 expression in EOC cell lines and nonmalignant control cells was detected. Cell proliferation, apoptosis and candidate target miRNA (miR‐149, miR‐183 and miR‐194) expressions were detected in circ‐PVT1 overexpression treated CAOV3 cells and circ‐PVT1 knock‐down treated SKOV3 cells. Furthermore, miR‐149 overexpression and miR‐149 knock‐down plasmids were transfected into circ‐PVT1 dysregulated CAOV3 cells and SKOV3 cells, respectively, and cell proliferation as well as apoptosis were detected.ResultsCirc‐PVT1 expression was increased in human EOC cell lines (CAOV3, SKOV3, SNU119 and OVCAR3) compared to human normal ovary surface epithelial cell line (HOSEpiC). In SKOV3 cells, cell proliferation was reduced at 48 and 72 h but cell apoptosis rate was increased at 48 h by circ‐PVT1 knock‐down. In CAOV3 cells, cell proliferation was increased at 48 and 72 h but cell apoptosis rate was decreased at 48 h by circ‐PVT1 overexpression. Besides, circ‐PVT1 negatively regulated miR‐149 but not miR‐183 or miR‐194 in SKOV3 and CAOV3 cells. Rescue experiments showed that miR‐149 knock‐down increased cell proliferation but decreased apoptosis in circ‐PVT1 knock‐down treated SKOV3 cells, while miR‐149 overexpression reduced cell proliferation but enhanced apoptosis in circ‐PVT1 overexpression treated CAOV3 cells.ConclusionCirc‐PVT1 enhances cell proliferation but inhibits cell apoptosis through sponging miR‐149 in EOC cells, which suggests that circ‐PVT1 may serve as a treatment target in EOC.

Mucinous borderline ovarian tumors with and without Intraepithelial Carcinoma: Differences in clinicopathologic features and fertility results

AbstractAimTo investigate the clinicopathologic characteristic and fertility results of patients with mucinous borderline ovarian tumors (MBOTs), and the effects of intraepithelial carcinoma (IECA) on them.MethodsFifty‐two patients treated for MBOTs with or without IECA were retrospectively analyzed.ResultsPatients with IECA were more frequently observed at stage Ic (3/12 vs 1/40, P = 0.034) and accompanied by microinvasive carcinoma (3/12 vs 1/40, P = 0.034). The detected rate of IECA by intraoperative frozen section (5/12, 41.7%) was much lower than that of MBOTs (82.5%, P = 0.010). About 61.5% patients in our study underwent fertility‐sparing surgery. Follow‐up information was retained completely in 41 patients. And all four tumor recurrences were observed (9.8%) in conservative surgery group in 66 months, though there was no statistical association (P = 0.280). There were three patients who recurred more than once, even one occurred tumor‐related death. Only one recurrent patient was in IECA group (P > 0.05). However, patients with IECA were more likely to receive adjuvant chemotherapy (3 of 12 vs 0 of 40, P = 0.010) and surgical staging (75% vs 52.5%, P = 0.200). As for fertility results, nine patients wished to be pregnant and seven of them (77.8%) were successful.ConclusionFor young patients with MBOTs, fertility results are satisfactory after conservative surgery. But patients should be fully informed about the relative high recurrent rate. And IECA has no statistical negative effects on MBOTs till now, but a long‐term follow‐up is required.

Navigating the landscape of cervical cancer in India: Epidemiology, prevention, current status, and emerging solutions

AbstractCervical cancer poses a significant health burden for women worldwide, particularly in India. Despite global progress, India's mortality rate, with 79 906 deaths, remains disproportionately high at approximately 11.2 per 100 000 women compared to the global average of 7.1 per 100 000 women. India's NPCDCS and other initiatives focus on VIA screening for women aged 30–65. The National Health Policy 2017 emphasizes primary healthcare enhancement, allocating two‐thirds of the budget. Ayushman Bharat promotes universal health coverage, including Health and Wellness Centers and PM‐JAY. Initiatives like Ayushman Bharat and the National Cancer Grid offer hope for improved cancer care. Leveraging technology, strengthening infrastructure, integrating services, promoting awareness, and enhancing HPV vaccination are crucial. By addressing barriers, improving access, and fostering collaboration, the cervical cancer burden can be reduced, ensuring better health outcomes for women nationwide.

Influence of COVID‐19 on the clinical characteristics of patients with uterine cervical cancer in Japan: A single‐center retrospective study

AbstractAimThis study investigated the impact of coronavirus disease 2019 (COVID‐19) on the clinical characteristics and interregional movement of patients with uterine cervical cancer.MethodsThis study included 1189 patients who underwent treatment for cervical cancer, including cervical intraepithelial neoplasm and adenocarcinoma in situ, at our hospital in Tokyo, Japan, in 2017–2018 and in 2021, before and after the pandemic, respectively. The patients' clinical information was compared during both periods. The clinical stage was unified using the International Federation of Gynecology and Obstetrics (FIGO) 2008 staging.ResultsThe number of patients treated for cervical cancer was 355, 420, and 414 in 2017, 2018, and 2021, respectively. The percentage of invasive carcinomas significantly increased from 158 (44.5%) and 196 (46.7%) to 219 (52.9%) (p = 0.049). In all periods, no significant differences were observed in median age, histological type, and treatment. The proportions of FIGO Stage IA1 were significantly elevated from 3.9% and 3.8% to 11.4% (p < 0.001). The percentage of patients from prefectures other than Tokyo significantly increased from 34.9% to 40.8% (p = 0.049). Furthermore, the proportion of patients with invasive carcinoma in private clinics increased from 28.0% to 37.9% (p = 0.014).ConclusionsThe number of patients with invasive carcinoma and the percentage of patients with invasive carcinoma referred from private clinics increased, indicating that the COVID‐19 pandemic influenced patients to delay consultations. Furthermore, the surge in patients from other prefectures indicates that medical resources were more limited in rural areas, another impact of COVID‐19.

Carcinomatous meningitis from recurrent glassy cell carcinoma of the uterine cervix—A case report

AbstractCarcinomatous meningitis presents with a variety of neurological symptoms and has a poor prognosis. We encountered a case of carcinomatous meningitis from cervical cancer. A 30‐year‐old patient was diagnosed with cervical cancer (glassy cell carcinoma), stage IIB. She underwent radical hysterectomy and chemoradiotherapy. Nine months later, the disease recurred with iliac lymph node and right lung metastases. The patient received chemotherapy; however, after seven cycles, the lung lesions increased. The patient responded to supportive care; nevertheless, symptoms including headaches developed and were followed by diplopia. A contrast‐enhanced magnetic resonance image of the head confirmed the diagnosis of carcinomatous meningitis. She was transferred to the palliative care unit and died approximately 1 week later. Carcinomatous meningitis has a poor prognosis and is difficult to treat; however, early diagnosis may provide meaningful time to patients. Therefore, attention must be paid to meningeal irritation and neurological symptoms.

Clinical presentation, treatment, and outcomes associated with vaginal intraepithelial neoplasia: A retrospective study of 118 patients

AbstractThe incidence of vaginal intraepithelial neoplasia (VAIN) is increasing annually; however, the reported values are likely underestimated. Risk factors for VAIN include advanced age, human papillomavirus (HPV) infection, history of hysterectomy, and simultaneous or previous cervical intraepithelial neoplasia (CIN) or cervical cancer cervical cancer. The most common presentation is abnormal cytology without clinical symptoms. Despite various treatment modalities available, the rate of disease recurrence is high, and its malignant potential has been documented. This study aimed to examine demographic and clinical characteristics and associated treatment outcomes of patients with VAIN. We retrospectively reviewed clinicopathologic data and clinical outcomes of patients diagnosed with VAIN at a single center between January 2010 and December 2017. Overall, 118 patients were included (average age 49.81 ± 9.77 years; range, 26–70 years). The distribution of the histologic grade was as follows: VAIN1, 30.5%; VAIN2, 41.5%; and VAIN3, 28.0%. In total, 97 (82.2%) patients had either prior or simultaneous cervical lesions, CIN (35.6%), or cervical cancer (55, 46.6%). A total of 100 cases (84.7%) were diagnosed using colposcopy and 18 (15.3%) were diagnosed by pathological accident after hysterectomy. Thin‐prep cytology test (TCT) results were available for 112 (94.9%) patients, and 111 (94.1%) patients had abnormal cytology findings. Most patients were confirmed as HPV positive (115, 97.5%), and 84 (71.2%) patients were confirmed as positive for high‐risk HPV types. Forty‐two (35.6%) patients underwent hysterectomy before VAIN diagnosis, and the median interval between hysterectomy and VAIN diagnosis was 26.5 (range: 3–68) months. Most surgical indications were HPV‐related diseases (34, 80.9%), such as CIN (8, 19.0%) or cervical cancer (26, 61.9%). Eight patients had no history of cervical lesions. A total of 100 patients underwent initial treatment. During the median follow‐up period of 29 (range: 9–96) months, 78 (78%) patients experienced disease remission after initial treatment, 7 (7%) experienced disease recurrence, 10 (10%) had persistent disease, and 5 (5%) had progressive disease. Finally, two patients developed vaginal cancer without death. Colposcopy should be performed before vaginal hysterectomy for VAIN, particularly HPV‐related cases. The incidence of VAIN was 20% after hysterectomy owing to non‐HPV‐related lesions; thus, this part of the screening should not be discontinued. VAIN grade 2,3 and VAIN associated with CIN or cervical cancer are disease types more likely to recur and progress to invasive cancer; active medical intervention is recommended.

Symptomatic and asymptomatic venous thromboembolism after minimally invasive surgery for gynecological cancers

Abstract Aims To clarify the frequency of postoperative symptomatic and asymptomatic venous thromboembolism (VTE) in patients who underwent minimally invasive surgery (MIS) for gynecological cancers; and to identify the risk factors associated with pulmonary embolism (PE). Methods We analyzed data for patients with endometrial, cervical, or ovarian cancers who underwent MIS or open surgery between February 2012 and December 2021 at Mie University Hospital, Japan. Patients who required conversion to open surgery were excluded. We treated deep vein thrombosis (DVT), including distal DVT, with preoperative anticoagulation. In all cases, intra‐ and postoperative VTE prophylaxis with anticoagulation, intermittent pneumatic compression, and compression stockings were provided. Results Overall, 382 patients with gynecological cancers who underwent MIS were included. Approximately 90% of patients had stage I disease. Symptomatic and asymptomatic PE occurred in 0.2% and 1.5% of patients who underwent MIS, respectively. All patients who developed PE had DVT. In the MIS group, both DVT and PE occurred in seven cases each (1.8%). Conversely, in the open surgery group ( n  = 817), there were 19 (2.3%) and 13 (1.6%) cases of DVT and PE, respectively. DVT and PE incidence rates did not significantly differ between the MIS and open surgery groups (DVT: p  = 0.67, PE: p  = 0.80). Uni‐ and multivariate analyses revealed that an operative time >6 h was associated with PE ( p  = 0.034). Conclusions VTE incidence was low among patients with gynecological cancers who underwent MIS. VTE rates remained low following open surgery or MIS when appropriate anticoagulation was administered. However, caution should be exercised during prolonged surgeries.

Predictors of treatment failure after top‐hat procedure in squamous intraepithelial lesion

AbstractAimThe value of top‐hat procedure during loop electrosurgical excision procedure (LEEP) for squamous intraepithelial lesions had remained controversial. This study aimed to evaluate whether top‐hat specimens positive for cervical intraepithelial neoplasia (CIN) on histopathology can serve as an independent risk factor to predict treatment failure.MethodsWe reviewed the medical records of patients who underwent LEEP and top‐hat procedures in Peking University First Hospital between 2011 and 2016 and collected their follow‐up data until January 2019. We compared the pathological risk factor of treatment failure. Multivariate analysis was carried out to clarify the independent determinant of treatment failure. A Cox model was used to assess the influence of different variables on cumulative treatment failure rates.ResultsThis study included 295 cases for short‐term treatment failure, and among them, 178 cases were used to study the long‐term. The presence of CIN in top‐hat was relevant to short‐term treatment failure (OR = 9.64, 95% CI 2.55–36.4) despite a clear margin. On multivariate analysis, top‐hat result (OR = 3.58, 95% CI 1.30–9.89), age ≥ 50 (OR = 10.2, 95%CI 3.64–28.3) and post‐treatment HPV 16/18 infection (OR = 2.35, 95%CI 1.19–4.63) were independent risk factors in predicting short‐term failure. In the Cox model, these factors were also associated with higher cumulative failure rates.ConclusionThe current study supported the predictive value of top‐hat procedure in short‐term failure after LEEP. Typically, women with positive top‐hat need closer follow‐up despite their negative margin status. Older women with positive top‐hat findings and HPV 16/18 infections after the treatment suffer a higher risk of short‐term failure.

The difficulty to diagnose cervical cancer developing in the perinatal period with the first‐trimester cytology: A retrospective study

AbstractAimCytological cervical cancer screening for pregnant women is routinely performed and still plays an essential role in Japan because of the considerably low rate of human pappillomavirus (HPV) vaccination. Though almost all pregnant women undergo cytological screening at their first trimester, we experienced invasive cervical cancers (ICC) diagnosed during pregnancy or postpartum period. We investigated the characteristics of perinatally diagnosed ICCs to clarify the difficulty in diagnosis during the pregnancy.MethodsWe retrospectively reviewed the clinical data on ICC diagnosed during pregnancy or within 1 year after delivery from 2010 to 2018 at Hokkaido University Hospital.ResultsWe identified 18 ICC patients, and the median follow‐up period was 46.5 months. Among eight patients with negative for intraepithelial lesion or malignancy (NILM), the mean duration to reach ICC diagnosis was 10.7 months, seven had stage IB1 or worse, and one was dead. On the other hand, among 10 women with abnormal cytology, the mean duration for diagnosis was 1.4 months, and 6 had stage IB1 or worse, and 1was dead. In terms of the timing of the final diagnosis, 8 were during pregnancy and 10 in the postpartum periods. Among eight pregnant patients, three resulted in a preterm delivery (33, 34, and 35 gestational weeks), and four terminated their pregnancies. One decided to continue the pregnancy until the term period. We performed conization in one patient and hysterectomy in seven.ConclusionA part of cytological examinations of pregnant women may result in presumed false‐negative or underestimation, which keeps them away from the additional examination to find ICC.

Incidence and univariate models for lymphatic drainage disorders following management for cervical cancer

AbstractAimTo clarify the incidence of lymphatic drainage disorders (LLD) after treatment for cervical cancer (CC) and to establish univariate models for their occurrence.MethodsA total of 263 eligible patients with CC were identified between 2010 and 2019. We conducted a case–control study and divided the study population into two subsamples of 12 and 251 CC survivors based on the presence/absence of LLD, respectively. The cumulative incidence was evaluated using the Kaplan–Meier method. Univariate models based on Pearson correlation coefficient were used to evaluate associations between explanatory variables and LLD.ResultsThe cumulative incidence of LLD began at 3.3% after the 7‐month follow‐up, reaching a plateau of 21.2% between 130 and 250 months of follow‐up.We detected correlation between LLD and number of removed para‐aortic lymph nodes (r = −0.39), number of pelvic lymphadenopathies (r = 0.16), pelvic lymphadenectomy (PL) (r = 0.16), age at diagnosis of CC (r = −0.1) and primary surgery (r = 0.1).ConclusionWe observed a cumulative incidence of LLD of 21.2%, which is in accord with other retrospective studies. Number of removed para‐aortic lymph nodes, number of pelvic lymphadenopathies, PL, age at diagnosis of CC and primary surgery were the most influential clinical factors associated with the occurrence of LLD in CC survivors.

Global research trends and focus areas in gynecologic oncology education: A bibliometric and network visualization study

Abstract Background Gynecologic cancers, comprising 14.4% of newly diagnosed cancer cases in women globally, are substantial causes of both mortality and morbidity, with a profound impact on the quality of life (QoL) of survivors. Therefore, it is crucial to strengthen education for both healthcare providers and patients. However, there remains a limited amount of comprehensive, systematic analysis on global research trends and key developments in this area, so this study aims to investigate global research trends and key focus areas in gynecologic oncology education through bibliometric analysis and network visualization, providing data‐driven support and valuable academic insights for future research. Method Articles on gynecologic oncology education published between 2014 and 2024 were retrieved from the Web of Science Core Collection database. We used bibliometric software (VOSviewer and CiteSpace) for quantitative analysis of co‐citation, co‐authorship, and co‐occurrence patterns, focusing on geographical distribution, key authors, references, and keywords. Results Research in this field has grown modestly since 2014, with annual publications exceeding 10 only after 2018. The author's analysis indicates that Ignacio Zapardiel, Lisa Singer, Manchanda, Ranjit and others are the core authors in this field. Western nations such as the United States and Germany lead in publication volume and citation impact, while Asian countries rarely appear in leading rankings. Keyword analysis indicates a recent focus on “education” within training frameworks. Conclusion Gynecologic oncology education remains nascent yet promising. Fostering international interdisciplinary collaboration—especially with Asian nations—is critical. Future priorities include high‐fidelity bioprinting, intraoperative navigation systems, multicenter technology standardization, specialized sexual health rehabilitation, and culturally adapted interventions.

A case of nasal septal perforation caused by bevacizumab for advanced cervical cancer

AbstractNasal septal perforation caused by bevacizumab is rarely reported in other cancers such as ovarian cancer and breast cancer, but it has not been reported in cervical cancer. A 48‐year‐old woman with a medical history of chronic allergic rhinitis was diagnosed stage 4B (T2bN1M0) cervical cancer and paclitaxel and carboplatin along with bevacizumab (triweekly) were administered. After eight courses of chemotherapy, nasal septal perforation was noted. The possibility of nasal septal perforation by bevacizumab was considered by excluding other causes. We report the first case of nasal septal perforation caused by bevacizumab for advanced cervical cancer.

Ovarian surveillance including endometrial cytology for patients with hereditary breast and ovarian cancer before risk‐reducing salpingo‐oophorectomy: A retrospective analysis

AbstractAimOvarian surveillance in women with hereditary breast and ovarian cancer who do not undergo risk‐reducing salpingo‐oophorectomy has been controversial. Therefore, this study aimed to demonstrate the clinical features of ovarian surveillance at our institution using a technique that combines serum cancer antigen 125 measurements, transvaginal ultrasonography, and uterine endometrial cytology.MethodsWe retrospectively examined 65 women, who had not undergone risk‐reducing salpingo‐oophorectomy diagnosed with hereditary breast and ovarian cancer between 2000 and 2021 at our hospital. Clinical information was obtained and analyzed through a chart review. The details of the treatment course were reviewed for patients who had developed ovarian cancer.ResultsOverall, 5 of the 65 women were diagnosed with ovarian cancer based on abnormal findings during periodic surveillance. All patients who developed ovarian cancer were asymptomatic, even if the cancer was at an advanced stage. Two of the 65 patients had endometrial cytology abnormalities, both of whom had ovarian cancer. All patients who developed ovarian cancer underwent primary debulking surgery, and complete gross resection was achieved. None of the patients experienced ovarian cancer recurrence.ConclusionsThe ovarian surveillance strategy at our institution for women with hereditary breast and ovarian cancer who do not undergo risk‐reducing salpingo‐oophorectomy can identify asymptomatic ovarian cancer and contribute to achieving complete gross resection during primary surgery. Ovarian surveillance may contribute to a reduction in ovarian cancer mortality.

Potential preoperative three‐dimensional computed tomography for para‐aortic lymphadenectomy in gynecological malignancies

Abstract Background The evaluation of anatomical abnormalities involving urinary vessel variations prior to para‐aortic lymphadenectomy in gynecological malignancies is challenging. In this context, the utility of preoperative three‐dimensional (3D) computed tomography (3DCT) angiography in improving surgical outcomes was examined. Methods This retrospective study evaluated the utility of 3DCT in patients who underwent para‐aortic lymphadenectomy between January 2023 and November 2024. 3D fusion images were constructed from the arterial phase, CT‐venography, and CT‐urography. A total of 72 patients were included and divided into two groups: non‐3DCT and 3DCT. Outcomes included detection rates of arterial, venous, or urinary tract variations and surgical outcomes, including complications, in both groups. Results The 3DCT group included 14/34 (41.2%) cases with renal vessel variations and two cases (5.9%) with double ureters; the non‐3DCT group did not detect any anatomical abnormalities. In the 3DCT group, renal vessel and urinary tract variations were clearly shown. Postoperative complications tended to be slightly higher in the non‐3DCT group, including lymphocyte infection, chylous leakage, and bowel obstruction. Postoperative CT revealed reduced contrast in the lower pole of the right kidney in the 3DCT case with the most complex urinary vessel variations. Furthermore, in the 3DCT group, 8/34 (23.5%) unilateral or bilateral renal arteries were located caudally to the lower edge of the renal vein. Conclusion In gynecological malignancies, 3DCT before para‐aortic lymphadenectomy seems superior in identifying urinary vessel variations over conventional contrast‐enhanced CT; thus, aiding realistic preoperative simulations and potentially reducing surgeons' burden and perioperative complications.

Overexpression of VEGF165 is associated with poor prognosis of cervical cancer

AbstractBackgroundCervical cancer is a major health hazard to Indian women. Human papillomavirus (HPV) infection is an established risk factor for cervical carcinogenesis. However, understanding the cervical cancer biology beyond HPV infection is very crucial to predict aggressive behavior, prognosis, treatment response and survival. In the present study, we explored the role of vascular endothelial growth factor A (VEGFA) isoforms, VEGFC and VEGFD in cervical cancer progression and its association with HPV 16 and 18 infections.Material and MethodsA total of 110 cervical cancer tissues and 50 normal cervical tissues were collected for the study. Reverse transcription‐polymerase chain reaction was employed to analyze tissue VEGFA isoforms, VEGFC and VEGFD expression.ResultsVEGF165 was significantly higher, whereas VEGFC and VEGFD were significantly lower in malignant cervical carcinoma tissues as compared to normal cervix tissues. Expression levels of VEGF121 and VEGFC were significantly associated with type of tumor growth while VEGF165 was significantly associated with lymph node metastasis. VEGF165 transcript levels were significantly higher in patients with squamous cell carcinoma (SCC) and developed recurrence. Most strikingly, higher VEGF165 expression was significantly associated with worst disease‐free survival (DFS) specifically in patients with SCC.ConclusionAssociation of VEGF165 with lymph node metastasis, disease recurrence and worst DFS indicated that VEGF165 is an important prognostic factor in cervical carcinogenesis.

Defecation disorder after anterior pelvic exenteration

Abstract Aim Anterior pelvic exenteration preserves rectal function. However, we observed postoperative defecation disorders, mainly frequent, divided, and watery stools, that are not transient and persist even after hospital discharge. No reports of defecation problems after anterior pelvic exenteration for gynecological malignancies exist. Therefore, we evaluated defecation status after anterior pelvic exenteration for gynecological malignancies. Methods Sixteen patients who underwent anterior pelvic exenteration in our department between 2012 and 2022 were included. For comparison, 132 radical hysterectomy and 13 radical cystectomy cases were also included. The postoperative defecation frequency and stool form were retrospectively evaluated. Results Patients who underwent rectal mobilization, laparoscopy, and prior hysterectomy had more frequent defecation 8–14 days postoperatively than those who did not. Laparoscopy and rectal mobilization were plausible causes of increased defecation frequency after anterior pelvic exenteration. Anterior pelvic exenteration with rectal mobilization was associated with more frequent defecation than radical hysterectomy and radical cystectomy, and laparoscopic‐anterior pelvic exenteration was associated with more frequent stools than laparoscopic‐ radical hysterectomy and laparoscopic‐radical cystectomy. However, there was no difference in defecation frequency among laparotomic‐anterior pelvic exenteration, laparotomic‐radical hysterectomy, and laparotomic‐radical cystectomy. Anterior pelvic exenteration with rectal mobilization and laparoscopic‐anterior pelvic exenteration had higher Bristol Stool Form Scale scores than radical hysterectomy and laparoscopic‐radical hysterectomy, respectively. Conclusions In anterior pelvic exenteration requiring the preservation of defecatory function, patients can experience postoperative frequent watery stools. Prospective studies are needed to validate these findings in larger cohorts.

Long‐term evaluation of renal function and neurogenic bladder following radical hysterectomy in patients with uterine cervical cancer

AbstractObjectiveThis study aimed to determine whether radical hysterectomy (RH) affects renal function.MethodsRenal function was followed up in 83 patients with stage IB1–IIB cervical cancer who underwent RH during 2006–2015. Serum creatinine (sCre) levels were measured preoperatively and every year postoperatively. Estimated glomerular filtration rate (eGFR) was calculated using sCre levels. Patients who were unable to urinate by themselves or whose residual urine was ≥100 mL were referred to a urologist with the diagnosis of neurogenic bladder (NB). The relationship between NB occurrence and changes in sCre level or eGFR was evaluated respectively.ResultsUrological intervention was required in 45 patients (54.2%), and self‐urethral catheterization was performed in 41 (49.3%) patients. The NB and clean intermittent catheterization (CIC) groups exhibited significant increases in sCre levels, which were not observed in the non‐NB or non‐CIC groups. In the non‐NB group, eGFR did not change following surgery. However, in the NB group, significant decreases in eGFRs were observed at postoperative 2 and 3 years and at final follow‐up. There was no difference in the incidence of cardiovascular events between patients with and without NB.ConclusionIn patients with NB following RH, a significant decrease in renal function was observed after postoperative 2 years.

Williams syndrome transcription factor promotes proliferation and invasion of cervical cancer cells by regulating PI3K/Akt signaling pathway

AbstractObjectiveThis study aimed to investigate the expression of Williams Syndrome transcription factor (WSTF) in cervical cancer (CC) tissues and cells, the effect on the proliferation, migration, invasion, and the molecular mechanism of WSTF in CC cells to find a new biomarker.Materials and MethodsThe expression of WSTF in tissues was detected by real‐time quantitative polymerase chain reaction (RT‐qPCR) and/or immunohistochemistry. Human CC cell lines and human normal cervical epithelial cell lines were detected by RT‐qPCR. Lentivirus‐mediated gene transfected in Siha/CaSki cells. The transfection efficiency of lentivirus was observed by a fluorescence microscope, RT‐qPCR, and western blot. After transfection, the proliferation of Siha/CaSki cells was detected by CCK‐8 assay and colony formation assay. The migration and invasion of Siha/CaSki cells were detected by transwell assay and wound healing assay. Western blot assay were used to detect the expression of WSTF and PI3K/Akt‐related proteins in Siha/CaSki cells.ResultsThe expression of WSTF in CC tissues was higher than that in adjacent tissues (p < 0.05). The expression of WSTF in CC cells was higher than that in normal cervical epithelial cells (p < 0.01). Downregulation of WSTF expression could inhibit the proliferation, migration, and invasion of CC cells (p < 0.01). WSTF overexpression activates PI3K/Akt signaling pathway (p < 0.01).ConclusionWSTF is highly expressed in CC tissues and cells, and downregulation of WSTF can inhibit the proliferation, invasion, and migration of CC cells by activating the PI3K/Akt signaling pathway. WSTF is a very promising new biomarker for CC.

Advances in therapeutic vaccines for treating human papillomavirus‐related cervical intraepithelial neoplasia

AbstractAimHuman papillomavirus (HPV) is the etiologic agent of the majority of cervical intraepithelial lesions (CIN) and cervical cancers. While prophylactic HPV vaccines prevent infections from the main high‐risk HPV types associated with cervical cancer, alternative nonsurgical and nonablative therapeutics to treat HPV infection and preinvasive HPV diseases have been experimentally investigated. Therapeutic vaccines are an emerging investigational strategy. This review aims to introduce the results of the main clinical trials on the use of therapeutic vaccines for treating HPV infection and ‐related CIN, reporting the ongoing studies on this field.MethodsData research was conducted using MEDLINE, EMBASE, Web of Sciences, Scopus, ClinicalTrial.gov, OVID and Cochrane Library querying for all articles related to therapeutic vaccines for the treatment of HPV‐related CIN. Selection criteria included randomized clinical trials, nonrandomized controlled studies and review articles.ResultsPreliminary data are available on the evaluation of therapeutic vaccines for treating cervical HPV infections and CIN. Despite having in vitro demonstrated to obtain humoral and cytotoxic responses, therapeutic vaccines have not yet clinically demonstrated consistent success; moreover, each class of therapeutic vaccines has advantages and limitations. Early clinical data are available in the literature for these compounds, except for MVA E2, which reached the phase III clinical trial status, obtaining positive clinical outcomes.ConclusionDespite promising results, to date many obstacles are still present before hypothesize an introduction in the clinical practice within the next years. Further studies will draw a definitive conclusion on the role of therapeutic vaccines in this setting.

Prognostic factors in women with cervical cancer stage IIIC1r treated with concurrent chemoradiotherapy

AbstractAimThe purpose of this study was to evaluate the prognostic factors of patients with stage IIIC1r cervical cancer who underwent concurrent chemoradiotherapy.MethodsA total of 134 patients treated with chemoradiotherapy for cervical cancer with pelvic and/or paraaortic lymph node metastasis (PALNM) were enrolled in this study. Clinical variables were investigated through review of the patients' medical records.ResultsThe 5‐year overall survival (OS) rate in patients with stage IIICr cervical cancer was 70.5%. Age, PALNM, parametrial invasion, T stage, pelvic side wall invasion, differentiation, lymphovascular space involvement and high squamous cell carcinoma antigen level (>8 ng/mL) were prognostic factors for survival. The 5‐year OS rate of patients with stage IIIC1r was 74.5%, and that of stage IIIC2r was 38.1% (P‐value = 0.012). The 5‐year OS rate of patients with stage IIIC1r with the presence of pelvic side wall invasion was 48.3% and that in its absence was 83.0% (P‐value < 0.001). The 5‐year OS rate of patients with stage IIIC1r with the presence of parametrial invasion was 68.9% and that in its absence was 82.4% (P‐value = 0.031). In multivariable analysis via backward conditional modeling, age, PALNM and pelvic side wall invasion were independent prognostic factors for survival of stage IIICr. Age and pelvic side wall invasion were independent prognostic factors for survival of stage IIIC1r cervical cancer.ConclusionIn stage IIICr cervical cancer, patients with PALNM, and/or pelvic side wall invasion can expect to have a poor prognosis. Particularly, pelvic side wall invasion in stage IIIC1r is an independent prognosis factor.

Treatment strategy for locally advanced squamous cell cervical cancer with clinically positive pelvic lymph nodes metastasis

AbstractAimTo determine the optimal treatment for locally advanced squamous cell cervical cancer with clinical positive pelvic lymph nodes metastasis (cN1).MethodsWe enrolled patients with squamous cell cervical cancer with 2008 FIGO stages IB, IIA, or IIB diagnosed with cN1, who were treated at Hyogo Cancer Center between April 2010 and December 2016. Patients with para‐aortic lymph nodes metastasis were excluded.ResultsOf the 69 eligible patients, 24 underwent concurrent chemoradiotherapy (CCRT), 11 underwent radical hysterectomy with pelvic lymphadenectomy (RH) with or without adjuvant RT, and 34 underwent neoadjuvant chemotherapy (NAC) followed by RH as initial treatment. The regimens of NAC included dose‐dense TC (paclitaxel 80 mg/m2, days 1, 8, 15; and carboplatin at an area under the curve = 6 on day 1, every 3 weeks) and dose‐dense TP (paclitaxel 80 mg/m2 on days 1, 8, 15; and cisplatin 75 mg/m2 on day 1, every 3 weeks). The median observation period was 57 (12–107) months. The 5‐year disease‐free survival rates of the CCRT, RH, and NAC groups were 78.7%, 63.6%, and 88.2%, respectively (p = 0.14). The 5‐year overall survival rates of the CCRT, RH, and NAC groups were 78.6%, 70.1%, and 94.1%, respectively (p = 0.11).ConclusionsWe recommend avoiding RH as primary treatment for cN1 with locally advanced squamous cell cervical cancer. Although CCRT should be considered for cN1, further studies are required to determine if NAC followed by RH will serve as an effective option.

Leptomeningeal metastasis from cervical cancer: Report of two cases and a review of the literature

AbstractLeptomeningeal metastases from cervical cancer are extremely rare, with only 24 cases reported in the English‐language literature. Leptomeningeal metastasis (LM) is usually a late event, but it can develop at any stage. A 44‐year‐old woman presented with vertigo, tinnitus, diminution of hearing, and a cervical tumor at the initial visit. She underwent whole brain radiotherapy and systemic chemotherapy. Five months after the initial visit, her condition deteriorated rapidly and she died. A 49‐year‐old woman underwent surgery and pelvic radiotherapy for cervical cancer. She underwent resection of lung metastases 2 years later and received systemic chemotherapy for lymph node metastases 4 years later. Five years after the initial visit, the patient suddenly presented with diplopia, headache, and vomiting; her clinical course was fulminant and she died. Most patients with LM present with diverse clinical manifestations and deteriorate rapidly despite multiple treatment modalities. Gynecologic oncologists should be aware of this rare complication.

Serous carcinoma of the uterine cervix: Clinicopathological features differing from serous carcinomas of other female organs

AbstractAimSerous carcinoma of the uterine cervix (USCC) is a very rare malignant tumor, while this histological subtype is common in the ovary, fallopian tube, uterine corpus and peritoneum. Because of its rarity, details of the clinicopathological features of USCC are largely unknown. We retrospectively analyzed the clinicopathological characteristics of five cases of pure USCC.MethodsWe reviewed the medical records and pathological specimens of five USCC cases who were treated at the Gynecology Service of the National Hospital Organization Kyushu Cancer Center, Japan, between 2000 and 2017. The clinicopathological features were also compared with those of serous carcinomas of the endometrium and ovary who were treated during the same period.ResultsFive patients were treated at our hospital between 2000 and 2017. Three tumors were stage IB1, one was stage IIB, and one was stage IVB. The median follow‐up time was 104 months (range 26–210). Four patients other than stage IVB were treated with radical hysterectomy and have been free of relapse. One patient with stage IVB tumor was treated with platinum‐based combination chemotherapy and is currently on maintenance therapy with bevacizumab and remains free of relapse.ConclusionUSCC has a distinctive clinicopathological feature that differentiates it from serous carcinomas of other female organs. USCC had been thought to be a poor prognostic disease; however, it could be curable if it is not accompanied by lymph node metastasis or peritoneal dissemination. We might conquer USCC even if it is accompanied by lymph node metastasis with the use of multimodal therapy.

High post‐treatment serum soluble receptor‐binding cancer antigen expressed on SiSo cells (sRCAS1) levels is associated with poor survival of patients with cervical cancer

AbstractAimReceptor‐binding cancer antigen expressed on SiSo cells (sRCAS1) is responsible for induction of selective immunosuppression. In addition, preclinical studies have shown that sRCAS1 levels may reflect cancer aggressiveness. The main aim of our study was to analyze pre‐ and post‐treatment levels of sRCAS1 in the sera of patients treated for cervical cancer and to evaluate whether the levels change during treatment and their impact on patient prognosis.MethodsThe study included 49 patients suffering from cervical cancer. The early stage cervical cancer patients (14) were treated surgically, while the advanced stage patients (35) underwent radiochemotherapy. Serum sRCAS1 levels were evaluated both before and after intervention with the use of the ELISA method.ResultsWe have found that median serum sRCAS1 levels of patients before intervention were not significantly different from the levels assessed after intervention. There were also no differences when pre‐ and post‐treatment levels were compared within the group of early and of advanced stage patients. Serum sRCAS1 levels were not influenced by either the histopathological type of the tumor or the methods of treatment. High post‐intervention sRCAS1 levels indicated shortened OS when compared to low sRCAS1 levels. Neither pre‐intervention sRCAS1 levels nor the alteration in sRCAS1 levels during treatment were associated with patient prognosis. In multivariate analysis, post‐treatment sRCAS1 levels and clinical stage of cervical cancer remained as independent predictors of survival.ConclusionHigh post‐treatment serum sRCAS1 level in cervical cancer patients seems to be a negative prognostic factor for patient overall survival.

Depth of Invasion of 13 mm or Greater Accurately Predicted the Risk of Having a Node Positivity in Lymphadenectomy for Squamous Vulvar Cancer

ABSTRACT Aim To analyze factors related to lymph node involvement in patients with squamous vulvar cancer undergoing lymphadenectomy and wide local excision at the University Hospital in Campinas, Brazil. Methods A retrospective study involving 56 women treated between 2010 and 2022. The primary outcome was inguinal lymph node involvement (positive or negative). Clinical, operative, and pathologic variables were analyzed by appropriate tests. Kaplan–Meier curves were used to determine overall survival rate (OS). A receiver operating characteristic (ROC) curve was created to determine the optimal value of the depth of invasion for predicting node positivity. Results Of the 56 women who underwent surgery, node involvement was positive in 18 (32.1%). Where node was positive, the tumors were over 5 cm in 22.2% (versus 2.7%, p  = 0.035), had an depth of invasion equal to or deeper than 13 mm (13 mm+) in 62.5% (versus 14.3%, p  < 0.001), lymphovascular invasion in 33.3% (versus 11.8%, p  = 0.024), presented disease progression in 44.4% (versus 11.8%, p  = 0.019), and death in 77.8% (versus 31.6%, p  = 0.001). The 5‐year OS was 57.1% in the node‐negative and 8.6% in the node‐positive group, with most events occurring within the first 24 months. Depth of invasion 13 mm + increased the risk of node‐positivity 11 times (11.37;1.85–69.82), showing a predictive negative value of 83.3%, and accuracy of 78.4%. Conclusion The 13.0 mm cutoff for depth of invasion was independently associated with the risk of having a positive node, with an accuracy of 78.4%. The 5‐year OS was 8.6% in the node‐positive group, with most events within the first 24 months.

Screening and management of preinvasive lesions of the cervix: Good clinical practice recommendations from the Federation of Obstetrics and Gynaecologic Societies of India (FOGSI)

AbstractIn India, there are marked variations in resources for cervical cancer screening. For the first time, resource‐stratified screening guidelines have been developed that will be suitable for low middle‐income countries with similar diversities. The current article describes the process and outcomes of these resource stratified guidelines for screening and treatment of preinvasive lesions of cervix. Evidence from literature was collated and various guidelines were reviewed by an expert panel. Based on the level of evidence, guidelines were developed for screening by human papillomavirus (HPV) testing, cytology and visual inspection after application of acetic acid (VIA), and management of screen positive lesions in different resource settings. Expert opinion was used for certain country‐specific situations. The healthcare system was stratified into two resource settings – good or limited. The mode of screening and treatment for each was described. HPV testing is the preferred method for cervical cancer screening. VIA by trained providers is especially suitable for low resource settings until an affordable HPV test becomes available. Healthcare providers can choose the most appropriate screening and treatment modality. A single visit approach is encouraged and treatment may be offered based on colposcopy diagnosis (‘see and treat’) or even on the basis of HPV test or VIA results (‘screen and treat’), if compliance cannot be ensured. The Federation of Obsterician and Gynaecologists of India Good Clinical Practice Recommendations (FOGSI) GCPR are appropriately designed for countries with varied resource situations to ensure an acceptable cervical cancer prevention strategy.

Hysterectomy and bilateral adnexectomy using transvaginal natural orifice transluminal endoscopic surgery: The role of multichannel abdominal PORT and vaginal support ring

AbstractBackgroundAlthough transvaginal natural orifice transluminal endoscopic surgery (NOTES) is gaining importance, knowledge on transvaginal NOTES procedures in gynecologic practice is limited.ObjectiveWe aimed at evaluating the feasibility and safety of performing hysterectomy and bilateral adnexectomy (or bilateral salpingectomy) via transvaginal NOTES using a self‐developed multichannel abdominal port and vaginal support ring.Study DesignA prospective, single‐center, cohort pilot study was conducted from May to December 2017 in patients with benign uterine diseases or endometrial atypical hyperplasia or cervical intraepithelial neoplasia (n = 30) scheduled for laparoscopic hysterectomy. The procedure was performed using a self‐developed five‐channel port and a vaginal support ring.ResultsHysterectomy and bilateral adnexectomy (or bilateral salpingectomy) in all 30 cases (mean age: 51.43 ± 4.60 years and body mass index: 23.42 ± 1.45 kg/m2) were successfully performed completely under transvaginal NOTES. Mean operation time was 95.90 ± 14.60 minutes and mean blood loss during the procedure was 52.50 ± 19.20 mL. Average weight of specimen was 79.97 ± 35.48 g. Only one complication of bladder injury was noted and was rectified accordingly. Visual Analog Score (VAS) at first day after operation was 2.70 ± 0.72. After follow‐up for 4.50 ± 1.85 months, all the patients' vaginal stump healed well without scar formation.ConclusionOur study showed that use of multichannel abdominal port could make laparoscopic instruments easier to fix and operate wherein the vaginal support ring reduces the leakage of carbon dioxide pneumoperitoneum. There was no scar on the abdomen and VAS was much lower. This study also demonstrated cosmetic benefits and rapid postoperative recovery.

A case of synchronous high‐grade cervical intraepithelial neoplasia and metastatic squamous cell carcinomas of unknown primary in rectum

AbstractWe report a case of synchronous high‐grade cervical intraepithelial neoplasia (CIN) and metastatic squamous cell carcinomas (SCCs) of unknown primary in the rectum. A 74‐year‐old woman was diagnosed with CIN3 by biopsy of the uterine cervix. Magnetic resonance imaging showed two masses in the outer rectal wall. They were diagnosed as SCCs by transrectal biopsy from one mass. On surgical treatment, CIN3 and SCCs in the rectum were identified, respectively. Pathological analysis revealed that SCCs were observed in serosa of the rectum, not mucosa, indicating that these tumors were metastatic SCCs. Gene analysis showed HPV31‐positive and TP53 mutation in CIN3, and HPV16‐positive in rectal SCCs. Pretreatment examination did not detect the primary site of metastatic SCCs in the rectum. We diagnosed the patient with synchronous CIN3 and metastatic SCCs of unknown primary in the rectum. In this case, gene analysis was useful to clarify the relationship between CIN3 and SCCs.

A case of cervical clear cell carcinoma with serous component

AbstractCervical clear cell carcinoma (CCCC) is rare. This report describes the case of CCCC with a serous component. A 22‐year‐old woman presented with vaginal bleeding. A cervical tumor was discovered: pelvic magnetic resonance imaging revealed a tumor measuring 46 mm. Radical hysterectomy was performed based on the diagnosis of stage IB2 cervical cancer. After histological examination of the specimen revealed a coexisting invasive clear cell carcinoma (95%) and serous carcinoma (5%), five cycles of nedaplatin and irinotecan therapy were administered as postoperative adjuvant chemotherapy. Local recurrence in the vaginal vault was observed at 7 months after surgery. Radiation therapy and chemotherapy were administered. The patient is alive without evidence of recurrence at 26 months after surgery.

Positive surgical margin is an independent predictor of overall survival of patients with vulvar squamous cell carcinoma

AbstractAimIt is uncertain whether curative surgical treatment or a less radical surgery with adjuvant treatment should be provided to preserve function in patients with vulvar squamous cell carcinoma (SCC) that is adjacent to the urethra, anus, and vagina. The aim of this study was to investigate the surgical margin in patients with vulvar SCC with regard to local recurrence and overall survival.MethodsThirty‐four patients were identified as having a diagnosis of vulvar SCC without distant metastasis. They had been treated surgically with curative intent at the Cancer Institute Hospital. Clinical data were analyzed retrospectively.ResultsRates of 5‐year local recurrence‐free survival among patients with positive, <3‐mm, <5‐mm, <8‐mm, and ≥8‐mm surgical margins were 32%, 30.3%, 42.5%, 55.5%, and 73%, respectively. Rates of 5‐year overall survival of patients with positive, <3‐mm, <5‐mm, <8‐mm, and ≥8‐mm surgical margins were 15.5%, 53.8%, 58.8%, 67.6%, and 83.3%, respectively. In the multivariable analysis, a tumor size of more than 2‐cm (hazard ratio [HR] = 17.7, 95% confidence interval [CI] = 1.39–226) and a positive surgical margin (HR = 0.0092, 95% CI = 0.011–0.53) were risk factors for local recurrence, and a lymph node involvement (HR = 1.41, 95% CI = 0.31–6.43) and a positive surgical margin (HR = 0.0046, 95% CI = 0.011–0.53) were significant risk factors for overall mortality.ConclusionsTo improve the prognosis, thorough resection with an adequate surgical margin is needed. But narrow surgical margin may be acceptable, particularly to preserve the function of adjacent organs.

Prognostic factors and surgical treatment in vulvar carcinoma: Single center experience

AbstractAimVulvar carcinoma represents 3–5% of all female genital cancers; the main surgical treatment is radical vulvectomy and inguinal lymphadenectomy. The aim of this study is to analyze prognostic factors in the patients underwent to primary surgery for vulvar carcinoma.MethodsOne hundred and eighteen cases of vulvar carcinoma underwent surgery between 2006 and 2016 at Operative Unit of Gynecology and Obstetrics of Cannizzaro Hospital (Catania, Italy) were retrospective analyzed. Risk factors for relapse (age, tumor size, FIGO stage, type of surgery, lymphadenectomy, margins status, metastatic nodes and radiotherapy) were evaluated by logistic regression. Univariate analysis of prognostic factors (age, tumor size, FIGO stage, metastatic inguinal nodes and type of surgery) was obtained by Cox proportional hazard model. Overall survival was calculated by Kaplan–Meier curves either for the entire population and for comparison between positive and negative variables (margin status, nodes and radiotherapy) with log‐rank test to determine significance. Statistical significance was reached for P < 0.05.ResultsType of surgery (radical local excision vs. radical vulvectomy) and positive inguinal nodes were identified as risk factors for relapse. Positive inguinal nodes and positive margins were identified as prognostic factors either for overall survival and disease specific survival; tumor size greater than 4 cm was identified as prognostic factors for overall survival. Overall survival was 38.4% and it was significantly higher in the patients with negative margins and nodes.ConclusionsNodes status, resection margins, age and type of surgery represent prognostic factors have to be considered for adjuvant treatment in the patients affected from vulvar carcinoma.

Ovarian clear cell carcinoma with an immature teratoma component showing ARID1A deficiency and an identical PIK3CA mutation

AbstractWe herein report a case of ovarian clear cell carcinoma with an immature teratoma component that exhibited aggressive behavior. A 47‐year‐old woman presented with abdominal distention, and computed tomography detected a cystic mass on the right ovary. The resected mass had mural nodules, most of which showed a pale‐yellow appearance; some nodules had a heterogeneous cut surface with bright yellow and white areas. Histologically, the former nodules were composed of clear cell carcinoma, while the latter contained teratomatous tissues, such as immature skeletal muscle, adipose tissue, and enteric glands. The tumor was staged as pT1c. Despite adjuvant chemotherapy and additional lymph node dissection, she had local recurrence and multiple liver metastasis 6 months after the first surgery. The disease rapidly progressed, and she died 9 months after the first surgery. Clear cell carcinoma and immature teratoma both showed ARID1A deficiency and an identical PIK3CA mutation, which suggested their clonal relationship.

Evaluation of the feasibility of human papillomavirus sponge‐type self‐sampling device at Japanese colposcopy clinics

AbstractAimSelf‐sampling human papillomavirus (HPV) testing has been introduced for cervical cancer screening worldwide. In Japan, there are two types (brush and sponge) of HPV self‐sampling devices. However, the recommended type for cervical cancer screening remains unclear. This study aimed to evaluate the feasibility of the HPV self‐sampling device–sponge type (HSD‐ST). Additionally, we aimed to examine the positive rate (sensitivity) for cervical intraepithelial neoplasia (CIN) 2 or worse using the HSD‐ST. Finally, we aimed to perform a questionnaire survey regarding the usability of the HSD‐ST.MethodsWe included 165 women who underwent HPV testing at one of three gynecologic clinics. First, the women used the HSD‐ST and completed a questionnaire regarding its usability. Subsequently, they underwent physician‐sampling HPV testing and cytology. We examined the agreement rate of HPV positivity between self‐ and physician‐sampling HPV testing.ResultsThe HPV‐positive rates of self‐ and physician‐collected samples were 59.4% and 62.4%, respectively, with an overall concordance rate of 88.5% and a calculated kappa coefficient of 0.76, indicating high concordance. Moreover, the positive (sensitivity) rates for CIN2 or worse were 81.4% and 89.8% in the self‐ and physician‐collected samples, respectively.ConclusionsOur findings demonstrated the feasibility and usability of the HSD‐ST.

Assessment of long‐term sexual function of cervical cancer survivors after treatment: A cross‐sectional study

AbstractObjectivesThis study aimed to investigate the long‐term sexual function of patients with cervical cancer who underwent treatment and to explore influential factors.MethodsThis retrospective cross‐sectional study was conducted at Peking University First Hospital in (Beijing, China). A total of 207 patients, who were diagnosed with Stage IA‐IIA cervical cancer and had undergone surgical treatment (some patients had also been treated with adjuvant radiotherapy and chemotherapy) between January 2010 and August 2020, completed questionnaires via telephone. The median time since diagnosis was 54 (range, 13–138) months. Sexual function was assessed using the validated short form of Pelvic Organ Prolapse/Urinary Incontinence Sexual Questionnaire (PISQ‐12). The multivariate logistic regression analysis was performed to determine factors influencing sexual function after treatment.ResultsThe mean preoperative PISQ‐12 score was 39.42 ± 3.922, and the mean postoperative PISQ‐12 score was 32.60 ± 6.592, indicating a significant decrease in postoperative PISQ‐12 score compared with preoperation (p < 0.001). In total, 49.8% of the patients had sexual dysfunction after treatment. According to the results of the multivariate logistic regression analysis, longer follow‐up (months), ovariectomy, lack of hormone replacement therapy after ovariectomy and adjuvant radiotherapy were significantly associated with sexual dysfunction after treatment (p < 0.05). There was no significant correlation among surgical method, tumor stage, adjuvant chemotherapy, and sexual dysfunction after treatment.ConclusionsThe sexual function of cervical cancer survivors significantly decreased after treatment, which was related to the length of follow‐up, ovariectomy, and adjuvant radiotherapy. Hormone replacement therapy after ovariectomy can help patients to improve their sexual function.

The incidence of cervical cancer in women with postcoital bleeding and abnormal appearance of the cervix referred through the 2‐week wait pathway in the United Kingdom: A retrospective cohort study

AbstractAimTo determine the incidence of cervical cancer in women referred through the 2‐week‐wait pathway for postcoital bleeding and abnormal appearance of the cervix.MethodsA retrospective cohort study was conducted of women with postcoital bleeding, or abnormal appearance of the cervix referred to colposcopy clinics through the 2‐week‐wait pathway for suspected cervical cancer at Cambridge University Hospitals in the United Kingdom over 5 years. Women were identified from a departmental database. Clinical and demographic data were collected. Categorical data was analyzed with chi‐squared or Fisher's exact tests and predictive values were calculated.ResultsOf the 604 women referred, 1.16% were diagnosed with cervical cancer. None of the women who were up‐to‐date with cervical screening were diagnosed with cervical cancer, while 6.25% of women out‐of‐date with cervical screening or outside the screening age group were diagnosed with cervical cancer (p < 0.001). The positive predictive value for diagnosing cervical cancer was 1.70% for postcoital bleeding (95% confidence interval [CI] 0.64–3.7) and 0.31% for abnormal appearance of the cervix (95% CI 0.0008–1.7).ConclusionsThe incidence of cervical cancer in women referred through the 2‐week‐wait pathway for postcoital bleeding and abnormal appearance of the cervix is low. These referrals have considerable implications for both patients and clinicians, and have a low predictive value for diagnosing cervical cancer. In light of emerging evidence and changing practices, referral guidelines should be reviewed based on up‐to‐date data and current practices.

Whether preoperative hysteroscopy increases the dissemination of endometrial cancer cells: A systematic review and meta‐analysis

AbstractAimTo determine whether hysteroscopy (HSC) increases the risk of intraperitoneal dissemination in endometrial cancer patients.MethodsWe conducted a comprehensive review of multiple databases. Quality assessments of eligible studies were performed using the Newcastle‐Ottawa and Jadad scales. Positive peritoneal cytology (PPC) as the outcome of interest was compared between endometrial cancer patients with and without HSC. Odds ratios (ORs) with 95% confidence intervals (CIs) were calculated as a measure of effects.ResultsThree case–control studies and eight retrospective cohort studies included 3364 patients, of whom 1116 underwent preoperative HSC, which resulted in a significantly higher PPC rate (OR, 1.82; 95% CI, 1.31–2.54; p = 0.0004). I2 was 11%, and the heterogeneity was acceptable. The difference between the groups with stages I–II was statistically insignificant (OR, 1.50; 95% CI, 0.75–2.99; p = 0.25). When liquid was used as the uterine distension medium during HSC and the intrauterine pressure was controlled under 80 mmHg, the difference between the two groups was also insignificant (OR, 1.18; 95% CI, 0.50–2.79; p = 0.71). However, when the intrauterine pressure exceeded 80 mmHg, the difference between the two groups was statistically significant (OR, 2.18; 95% CI, 1.28–3.73; p = 0.004).ConclusionThis meta‐analysis indicates that preoperative HSC in patients with endometrial cancer may increase the risk of intraperitoneal dissemination of malignant cells, which may be associated with intrauterine pressure >80 mmHg but not with stages I–II. There is no reason to avoid HSC for the diagnosis of endometrial cancer, especially in early stages, but intrauterine pressure should possibly be controlled below 80 mmHg.

ITGA7, CD133, ALDH1 are inter‐correlated, and linked with poor differentiation, lymph node metastasis as well as worse survival in surgical cervical cancer

AbstractAimIntegrin alpha 7 (ITGA7) regulates cancer stemness and metastasis in several malignancies, while its role in cervical cancer is obscure. Therefore, the current study aimed to investigate the correlation among ITGA7, cluster of differentiation 133 (CD133), and aldehyde dehydrogenase isoform 1 (ALDH1), as well as their relation to tumor features and survival in cervical cancer patients.MethodsA total of 133 surgical cervical cancer patients were enrolled. Tumor ITGA7, CD133, and ALDH1 expressions were determined by immunohistochemistry (IHC). Furthermore, the clinicopathological features, disease‐free survival (DFS), and overall survival (OS) were collected.ResultsITGA7 expression positively related to CD133 expression (p = 0.040) and ALDH1 expression (p < 0.001). Besides, ITGA7 (p = 0.001), CD133 (p = 0.016), and ALDH1 (p = 0.009) high expressions linked with poor tumor differentiation; meanwhile, ITGA7 (p = 0.010) and ALDH1 (p = 0.004) high expressions correlated with more prevalence of lymph node metastasis. However, ITGA7, CD133, or ALDH1 expression was not associated with other clinicopathological features. Inspiringly, it was worth noting that ITGA7 (p = 0.009), CD133 (p = 0.041), and ALDH1 (p = 0.035) high expressions predicted unfavorable DFS; meanwhile, both ITGA7 (p = 0.021) and ALDH1 (p = 0.023) high expressions but not CD133 expression (p = 0.169) forecasted exasperated OS.ConclusionITGA7, CD133, ALDH1 are inter‐correlated, and linked with poor differentiation, lymph node metastasis as well as worse survival in surgical cervical cancer.

Is the extent of lymphadenectomy a prognostic factor in International Federation of Gynecology and Obstetrics stage II endometrioid endometrial cancer?

AbstractAimThis study aimed to evaluate the prognostic significance of adequate lymph node dissection (LND) (≥10 pelvic lymph nodes (LNs) and ≥ 5 paraaortic LNs removed) in patients with International Federation of Gynecology and Obstetrics (FIGO) stage II endometrioid endometrial cancer (EEC).MethodsA multicenter department database review was performed to identify patients who had been operated and diagnosed with stage II EEC at seven centers in Turkey retrospectively. Demographic, clinicopathological, and survival data were collected and analyzed.ResultsWe identified 284 women with stage II EEC. There were 170 (59.9%) patients in the adequate lymph node dissection (LND) group and 114 (40.1%) in the inadequate LND group. The 5‐year overall survival (OS) rate of the inadequate LND group was significantly lower than that of the adequate LND group (84.1% vs. 89.1%, respectively; p = 0.028). In multivariate analysis, presence of lymphovascular space invasion (LVSI) (hazard ratio [HR]: 2.39, 95% confidence interval [CI]: 1.23–4.63; p = 0.009), age ≥ 60 (HR: 3.30, 95% CI: 1.65–6.57; p = 0.001], and absence of adjuvant therapy (HR: 2.74, 95% CI: 1.40–5.35; p = 0.003) remained as independent risk factors for decreased 5‐year disease‐free survival (DFS). Inadequate LND (HR: 2.34, 95% CI: 1.18–4.63; p < 0.001), age ≥ 60 (HR: 2.67, 95% CI: 1.25–5.72; p = 0.011), and absence of adjuvant therapy (HR: 4.95, 95% CI: 2.28–10.73; p < 0.001) were independent prognostic factors for decreased 5‐year OS in multivariate analysis.ConclusionAdequate LND and adjuvant therapy were significant for the improvement of outcomes in FIGO stage II EEC patients. Furthermore, LVSI was associated with worse 5‐year DFS rate in stage II EEC.

Changes in Epithelial Ovarian Cancer Recurrence and Survival According to Treatment Paradigm Shifts

ABSTRACT Aim To evaluate oncologic outcomes in patients with epithelial ovarian cancer (EOC) amid evolving surgical and systemic therapy paradigms. Methods This retrospective cohort study included patients diagnosed with EOC from June 2003 to December 2020 at a single tertiary center, grouped by diagnosis period. Overall survival (OS) and progression‐free survival (PFS) were analyzed using the Kaplan–Meier and Cox regression analyses. Results A total of 763 patients were classified as 2003–2008 (Group 1, n  = 101), 2009–2013 (Group 2, n  = 207), and 2014–2020 (Group 3, n  = 455), reflecting changes in cytoreductive surgery and targeted therapies (bevacizumab and PARP inhibitors). Early‐stage diagnoses increased over time without statistical significance (Stage I–II: Group 1, 37.6% vs. Group 3, 46.6%; p  = 0.200). Group 2 showed greater use of interval debulking surgery (IDS), higher complete cytoreduction rates, and more first‐line chemotherapy cycles (all p  < 0.001). Group 3 represented the introduction of targeted therapies ( p  < 0.001 for both). IDS with residual (< 1 cm) was associated with poorer outcomes than complete/optimal primary debulking surgery (PDS) (hazard ratio 2.94, 95% confidence interval 1.5–5.8). Despite unchanged PFS, the 5‐year OS improved from 64.0% to 82.5% among patients with advanced‐stage disease ( p  = 0.024). Conclusions Over two decades, with the advent of targeted therapies, complete cytoreduction (especially in PDS) has increased. Although the use of IDS also increased, residual disease (< 1 cm) after IDS was associated with poorer outcomes. While PFS remained unchanged, 5‐year OS significantly improved among patients with advanced‐stage disease diagnosed in the most recent period.

Transvaginal natural orifice endoscopic surgery for extremely obese patients with early‐stage endometrial cancer

AbstractAimThe purpose of this study was to assess the feasibility and efficacy of transvaginal natural orifice transluminal endoscopic surgery (v‐NOTES) staging surgery for extreme obese patients with early‐stage type‐1 endometrial cancer.MethodsStudy included cases of extreme obese patients with early‐stage endometrial cancer who underwent v‐NOTES between January 2019 and June 2019 at a tertiary referral medical center. The following parameters were noted: patient age, body mass index (BMI), operating time, conversion to conventional laparoscopy or laparotomy, any intraoperative or postoperative complications, estimated blood loss, pre‐ and postoperative hemoglobin levels, postoperative pain scores of the patients using visual analogue scale (VAS) at 6th, 12th and 24th h, length of hospital stay and final pathology report.ResultsSix cases of extreme obese patients with early‐stage endometrial cancer underwent hysterectomy and bilateral salpingo‐oophorectomy via the transvaginal NOTES. These six patients had a mean body mass index of 51.4 kg/m2 (SD = 6,13). No conversion to conventional laparoscopy or even laparotomy was needed in any of these patients. No adjuvant therapy was needed since all of the patients had early‐stage endometrial carcinoma.ConclusionGiven the increased risk of surgical morbidity and mortality associated with increasing BMI, it is paramount importance to establish safe surgical approaches to gynecological pathologies. We think that v‐NOTES offers greater benefit to obese patients when performed by an experienced surgeon and v‐NOTES is a safe, effective and feasible minimally invasive surgery in extreme obese patients with early endometrial cancer.

Live Birth Outcomes After Extended or Repeated High‐Dose Medroxyprogesterone Acetate Therapy for Fertility‐Sparing Management of Endometrial Neoplasia: A Single‐Center Retrospective Case Series

ABSTRACT Aim To clarify live birth outcomes among women receiving extended or repeated high‐dose medroxyprogesterone acetate (MPA) therapy for fertility‐sparing management of atypical endometrial hyperplasia or endometrioid carcinoma grade 1. Methods We conducted a single‐center retrospective case series of 53 patients undergoing MPA therapy between 2005 and 2023. Patients were stratified into three groups: (i) complete response (CR) within 6 months (standard group), (ii) CR after extended treatment beyond 6 months (extended group), and (iii) CR after MPA retreatment for first intrauterine recurrence (retreatment group). Primary outcome was the live birth rate (LBR). Secondary outcomes included the effect of initial reproductive intentions, interval from CR to conception, recurrence rates, and recurrence‐free interval (RFI). Results LBRs were 33% (10/30) in the standard group, 8% (1/12) in the extended group, and 17% (2/12) in the retreatment group. Among eight patients undergoing MPA retreatment for a second or subsequent recurrence, none achieved live birth. Patients with an initial desire for prompt conception had significantly higher LBRs than those without (38% vs. 5%, p < 0.01). Median time from CR to conception leading to live birth was 12 months. Patients achieving live birth had significantly longer RFIs than those without ( p < 0.01). Conclusions Live birth is most likely when CR is achieved within 6 months of MPA therapy; nonetheless, extended or repeated MPA treatment may still result in live birth. These findings suggest the importance of appropriate patient selection and careful monitoring during extended or repeated therapy and attempting conception promptly in fertility‐sparing management of endometrial neoplasia.

Value of preoperative neutrophil–lymphocyte ratio and human epididymis protein 4 in predicting lymph node metastasis in endometrial cancer patients

AbstractAimTo investigate the value of pretreatment neutrophil–lymphocyte ratio (NLR), platelet–lymphocyte ratio (PLR), serum cancer antigen 125 (CA125) and human epididymis protein 4 (HE4) in predicting lymph node metastasis in patients with endometrial cancer.MethodsA retrospective analysis of 145 patients with endometrial cancer who were treated at the Peking University Cancer Hospital and Institute between October 2010 and November 2013 was performed. Preoperative NLR, PLR, serum CA125 and HE4 were assessed. Clinicopathological parameters were evaluated for LN metastasis using logistic regression. Receiver operating characteristic (ROC) curves were plotted and the optimal cut‐off values of NLR, PLR, CA125 and HE4 were calculated for predicting lymph node metastasis.ResultsThe levels of NLR, PLR, serum CA125 and HE4 were significantly higher in patients with lymph node metastasis than those without lymph node metastasis. Multivariate analysis showed that only the higher NLR and HE4 were independent predictors for lymph node metastasis (odds ratio, OR = 3.509, P = 0.016; OR = 1.446, P = 0.016). The optimal cut‐off values of NLR and HE4 for predicting lymph node metastasis were 2.50 (area under the curve, AUC = 0.809) and 80.4 pmol/L (AUC = 0.713). The sensitivity and specificity were 75.0% and 84.9% for NLR, 86.7% and 73.8% for HE4, respectively. When HE4 was combined with NLR to predict lymph node metastasis, the sensitivity and specificity were significantly improved.ConclusionPreoperative higher NLR and serum HE4 are predictors of lymph node metastasis in endometrial cancer, and the predictive value was superior to that of serum CA125.