Journal

Archives of Gynecology and Obstetrics

Papers (422)

Preoperative assessment of tumor size by MRI and ultrasound in cervical cancer: a large-scale retrospective comparative study

Abstract Purpose Accurate preoperative evaluation of tumor sizes is essential for guiding optimal treatment planning in cervical cancer. This study aimed to compare the accuracy of preoperative tumor size measurement between magnetic resonance imaging (MRI) and ultrasound. Methods A retrospective study was performed involving 925 patients diagnosed with cervical cancer who underwent primary surgical treatment between January 2020 and June 2025. The accuracy of these two imaging modalities was assessed by comparing their measurements to the maximum tumor diameter determined through postoperative pathological analysis. Results The Bland–Altman analysis showed that both ultrasound (mean difference: 1.50 mm) and MRI (mean difference: 0.61 mm) overestimated tumor size. In the paired subgroup of 757 patients who underwent both imaging modalities, the agreement rates between imaging and pathology for categorizing tumors into size groups were 65.8% for ultrasound and 67.6% for MRI ( p  = 0.360). Although MRI showed a significantly smaller mean measurement bias than ultrasound (0.73 mm vs. 1.37 mm; p  = 0.012), the proportion of large errors (> 10 mm) was not significantly different. Multivariate analysis indicated that tumors > 40 mm assessed by ultrasound (OR = 2.85) or MRI (OR = 2.72) were significantly associated with increased likelihood of measurement discrepancies > 10 mm. Conclusion While MRI exhibited a lower measurement error compared to ultrasound, both modalities showed comparable performance in tumor size staging. Furthermore, for tumors exceeding 40 mm in diameter as determined by preoperative imaging, clinicians are advised to integrate clinical examination to enhance the accuracy of staging.

Burden of CIN2+ diagnoses and conizations in women aged 18–45 years—a retrospective secondary data analysis of German statutory health insurance claims data

Abstract Purpose High grade cervical intraepithelial neoplasia (CIN2+) may progress to cervical cancer. They may be detected by screening and are usually treated by conization. This study aimed at assessing annual proportions of screening, prevalent and incident CIN2+ diagnoses, as well as proportions of (re-)conizations during 24 months follow-up after conization in Germany. Methods A descriptive retrospective claims data analysis of the years 2013–2018 was conducted using the InGef Research Database. Women aged 18–45 years with CIN2+ diagnoses were identified by ICD-10-GM codes (N87.1, N87.2, D06.-, and C53.-). Cervical conizations were identified by OPS codes (5–671.0* or 5–671.1*). Screening participation was identified by EBM codes (01730, 01733, 32819 or 32820). Annual proportions were calculated as women with the respective documented codes divided by all women in the respective age group per calendar year. Results Overall annual proportions of screened women spanned from 60.01 to 61.33% between 2013 and 2018. The overall annual prevalence of CIN2+ diagnoses (regardless of screening participation) ranged from 0.72 to 0.84% between 2013 and 2018, with highest proportions observed in women aged 27–45 years. Also, CIN2+ incidence was highest in women 27–45 years. Annual proportion of women undergoing conization was 0.24% in 2013 and 0.21% in 2018. During a 24-month follow-up period after conization, 2.91% of women underwent a re-conization 3 months or later after the initial conization. Conclusion This analysis demonstrates a considerable burden of CIN2+, conizations and re-conizations in Germany, especially in women aged 27–45 years. This highlights the need for intensified prevention efforts such as expanding human papillomavirus (HPV) vaccination.

Comparison of surgical and oncologic outcomes in patients with clear cell ovarian carcinoma associated with and without endometriosis

To compare clinical characteristics, surgical and oncologic outcomes of clear cell ovarian cancer among patients with cancer arising from endometriosis, cancer coexisting with endometriosis, and cancer without endometriosis. A retrospective chart review of patients diagnosed with clear cell ovarian cancer during January 1998-March 2013 was performed. All histopathology specimens were reviewed by a gynecologic pathologist and classified into one of the three following endometriosis status groups: arising group, coexisting group, or without group. The primary outcome was disease-specific survival (DSS). The secondary outcomes were progression-free survival, surgical morbidities, response rate, recurrence rate, and cancer-specific death. Finally, 249 patients were included. There were 82, 96, and 71 patients in the arising, coexisting, and without groups, respectively. Regarding baseline characteristics among groups, the without group was significantly older and had more advanced diseases. There was a significant difference in progression-free survival between the arising group and the without group (p = 0.003). Five-year progression-free survival rates were 62.8% in the arising group, 50.2% in the coexisting group, and 38.3% in the without group. DSS was not significantly different among groups. Multivariate analysis revealed ovarian surface invasion (HR = 2.76) and pelvic lymphadenectomy (HR = 0.39) to be independent prognostic factors for progression-free survival, whereas no remission after primary treatment (HR = 8.03) and pelvic lymphadenectomy (HR = 0.21) were prognostic factors for DSS. Intraoperative blood loss and residual tumor were significantly higher in the without group. Endometriosis status was found not to significantly influence surgical and oncologic outcomes in patients with clear cell ovarian cancer.

Development and psychometric properties of the human papillomavirus-quality of life (HPV-QoL) questionnaire to assess the impact of HPV on women health-related-quality-of-life

Abstract Purpose The HPV-Quality-of-Life (HPV-QoL) questionnaire was developed to determine the impact of Human-Papillomavirus (HPV) infection and related interventions on women health-related quality-of-life. This study provides the development and preliminary psychometric properties of a novel HPV-QoL questionnaire for adult women with HPV. Methods After reviewing literature and cognitive debriefing interviews in women who had experienced HPV-related conditions, instrument items and domains were developed. A draft questionnaire was pilot tested for comprehension and ease of completion. Psychometric evaluation of the final HPV-QoL scale was conducted in a psychometric study including 252 adult women derived to our centre by a positive HPV test in the cervical cancer screening program and/or presenting genital warts. Results The present study reveals that the HPV-QoL questionnaire, structured in four domains: general well-being [including psychological well-being and social well-being subdomains], health, contagiousness and sexuality, showed good metric properties of feasibility irrespective of age or educational level, and time to administer was less than 5 min. Internal consistency and temporal stability (reliability) showed values above the acceptable standards. The instrument showed its concurrent validity by means of a significant correlation with mental and sexual existing instruments; GHQ-12 and FSFI questionnaires, respectively, and also known groups validity showing significant differences among the subgroups regarding either sexual dysfunction or mental deterioration. Conclusion This study provides an HPV-QoL questionnaire with an innovative patient-reported outcomes specific measurement tool to assess HRQoL in women with HPV infection. The present study suggests this questionnaire has satisfactory psychometric properties, including validity and reliability. Results support the use of the HPV-QoL questionnaire as a HRQoL measurement instrument for daily medical practice and clinical research.

Vaginal natural orifice transluminal endoscopic surgery for malignant ovarian tumors: a single-institution study

Vaginal natural orifice transluminal endoscopic surgery (vNOTES) is an established access technique for gynecological surgeries, but its utility in ovarian cancer surgery is not well-established. This was a single-institution retrospective cohort study of patients who underwent vNOTES surgery and had malignant tumors arising from or involving the ovary on final histology. Preoperative, intraoperative and immediate postoperative outcomes were collected. Oncological outcomes of recurrence and overall survival were also analyzed. A total of 19 patients were included for analysis: 4 patients had fertility-sparing surgery, 12 had primary staging surgery, 1 had restaging surgery and 2 patients had interval debulking surgery. In the primary staging surgery group, hysterectomy was performed in all patients, omentectomy in a third of the patients, and pelvic lymph node dissection in a quarter of the patients. Only one intraoperative complication of high blood loss was seen, in a patient who was a known hemophilia carrier. Pain scores were mostly zero at 12 and 24 h post-operatively, and most patients were discharged on postoperative day 1 or 2. There were no readmissions for postoperative complications or disease recurrence within 30 days. Median follow-up time was 26.4 months in the whole cohort (interquartile range, 6.3 to 30 months), during which there were 4 cases of recurrence and no deaths. vNOTES is a feasible and versatile technique for ovarian cancer surgery, with low rates of intraoperative and postoperative complications, short length of stay, and favorable short- to medium-term oncological outcomes.

Loop electrosurgical excision procedure (LEEP) under local anesthesia: a retrospective analysis of 435 subsequent cases under a quality assurance program

Abstract Purpose The aim of this study is to analyze a quality assurance program regarding the switch from loop electrosurgical excision procedure (LEEP) in general anesthesia (GA) to local anesthesia (LA) regarding patients’ perioperative pain levels, patients´ satisfaction, as well as resection margins. Methods We performed a single-center retrospective analysis of our quality assurance program including all patients undergoing LEEP at the Department of Obstetrics and Gynecology, Ordensklinikum Linz and Konventhospital Barmherzige Brueder Linz, from January 2021 to June 2024. 435 patients were questioned postoperatively after being treated with LEEP in LA regarding the perioperative pain as measured by a numeric rating scale (NRS) and patients’ satisfaction. Clinical data were collected from the patients’ electronic chart to investigate further parameters. Results Mean perioperative pain levels were stated as 1.3 (1.9). Five perioperative complications were reported. In seven out of 435 cases (1.6%) an inpatient readmission or a revision surgery under GA had to be performed. A R0 resection rate of 81.4% could be achieved. In 9.7% and 8.3% a R1 resection rate was reported on the ectocervix and on the endocervix, respectively. 95.3% of patients would choose LEEP in LA as their preferred method of anesthesia for a possible subsequent surgical LEEP procedure. Conclusions Our study showed that the implementation of LEEP in LA was successful at our department as a new standard of care, resulting in a high R0 resection status and a high level of patients’ satisfaction. We encourage physicians and organizations to switch from GA to LA when performing LEEP for cervical dysplasia.

TCGA molecular subgroups and FIGO grade in endometrial endometrioid carcinoma

International Federation of Gynecology and Obstetrics (FIGO) grade is a crucial factor in the current system for the risk stratification of endometrial endometrioid carcinoma (EC). The Cancer Genome Atlas (TCGA) demonstrated four molecular prognostic subgroups for EC: POLE (good prognosis), microsatellite-instable (MSI, intermediate prognosis), copy-number-high (CNH, poor prognosis), and copy-number-low (CNL, variable prognosis). To assess how the prevalence of the TCGA molecular subgroups changes from low-grade (G1-2) to high-grade (G3) EC, to understand how it may affect the current risk-assessment system. A systematic review and meta-analysis was carried out by searching seven electronic databases from January 2013 to September 2019 for studies assessing the TCGA classification G1-2 and G3 EC. Pooled prevalence of the TCGA subgroups was calculated in EC. The association of each subgroup with grade was assessed using odds ratio (OR), with a significant p value < 0.05. Nine studies with 3185 patients were included. G3 EC showed significantly higher prevalence of the POLE subgroup (12.1% vs 6.2%; OR = 2.13; p = 0.0001), of the MSI subgroup (39.7% vs 24.7%; OR = 2.15; p = 0.0003) and of the CNH subgroup (21.3% vs 4.7%; OR = 5.25; p < 0.00001), and significantly lower prevalence of the CNL subgroup (28% vs 63.5%; OR = 0.2; p < 0.00001) than G1-2 EC. The prevalence of the TCGA subgroups is not in accordance with the prognostic value of FIGO grade, indicating that the current risk stratification of EC will be heavily affected by molecular signature.

Prognostic factors for malignant tumors arising from mature cystic teratomas: a study involving the Kansai Clinical Oncology Group (KCOG-G1305s study)

Current data regarding prognostic factors for malignant tumors arising from mature cystic teratomas (MT-MCTs) and effective treatments are insufficient. This study aimed to identify risk factors for MT-MCTs of the ovary. Tumor samples diagnosed as MT-MCTs were collected from 13 institutions that participated in the Kansai Clinical Oncology Group. Based on the clinicopathological features and prognoses of the tumors, risk factors for progression and death were statistically assessed using univariable and multivariable analyses. Among the 60 tumor samples collected, 56 were diagnosed as MT-MCTs. Four samples were excluded based on the results of a central pathological review. Nine histological types, including squamous cell carcinoma, were diagnosed. Thirty of the 56 included samples were classified as International Federation of Gynecology and Obstetrics (FIGO) stage I, seven were classified as FIGO stage II, 18 were classified as FIGO stage III, and one was classified as FIGO stage IV. The 5-year progression-free survival and overall survival probabilities for stage I disease were significantly higher than those for stages II-IV disease (p < 0.001). In the multivariable analysis, surgery with residual tumor margins was a prognostic factor for progression, and FIGO stages I-IV and the absence of adjuvant therapy were prognostic factors for death. Surgery without residual tumor margins and adjuvant therapy may be promising treatments for advanced-stage MT-MCTs.

Fertility-sparing surgery upon reproductive and oncologic results in ovarian cancer patients stage I (FIGO): a systematic review

Abstract Purpose This systematic review evaluates the oncologic and reproductive outcomes of fertility-sparing surgery (FSS) in women diagnosed with stage I ovarian cancer, as classified by the International Federation of Gynecology and Obstetrics (FIGO). This study aimed to assess the safety and effectiveness of FSS in preserving fertility without compromising survival outcomes. Methods A systematic search was conducted in MEDLINE (PubMed), SCOPUS, and Google Scholar for studies published in English from 2014 onward. Studies involving women under 50 with stage I ovarian cancer who opted for FSS were included. Data extraction focused on oncologic outcomes (recurrence and survival rates) and reproductive outcomes (pregnancy and live birth rates). Study selection followed PRISMA guidelines. The primary outcomes evaluated in this review were reproductive outcomes (pregnancy and live birth rates, including use of assisted reproductive technologies) and oncologic outcomes (recurrence rates, overall survival, and disease-free survival) following fertility-sparing surgery in women with FIGO stage I ovarian cancer. Results Seventeen studies comprising 1030 patients met the inclusion criteria. Pregnancy success rates ranged from 25% to 91.3%, with live birth rates exceeding 80% in most studies. Spontaneous conception was predominant, though 3.7% to 28% of patients required assisted reproductive technologies (ARTs). Despite 58% of patients expressing a desire for future pregnancy, only 13% actively attempted conception. Recurrence rates varied from 3% to 33.3%, with most studies reporting between 8 and 15%. Overall survival ranged from 88 to 100%, and disease-free survival remained above 90%. The highest recurrence was observed in mucinous ovarian carcinoma and FIGO Stage IC2/IC3 subtypes. Conclusion FSS in stage I ovarian cancer is a viable alternative to radical surgery in carefully selected patients, with favorable oncologic and reproductive outcomes. However, recurrence risks and fertility challenges highlight the need for multidisciplinary counseling, long-term surveillance, and further research to refine selection criteria and optimize fertility preservation techniques.

The Charité protocol for surveillance, treatment and after-care management in women with Lynch syndrome

Abstract Background Lynch syndrome (LS) is the most common inherited cancer syndrome, caused by germline mutations in mismatch repair (MMR) genes such as MLH1, MSH2, MSH6, and PMS2. While primarily associated with colorectal cancer, LS significantly impacts gynecological oncology, with increased risks for endometrial and ovarian cancers. Despite its clinical relevance, structured counseling and surveillance programs tailored to LS patients in gynecology are lacking. Objective and methods This study presents the first structured gynecological outpatient consultation program for LS patients in Germany, established at Charité—Universitätsmedizin Berlin in August 2021. The aim was to develop an individualized, multidisciplinary framework for surveillance, therapy, and follow-up care, addressing the specific needs of different patient cohorts. Between August 2021 and December 2023, clinical data from 40 LS patients were collected and analyzed descriptively. From this experience, we furthermore concluded a guideline for the care of individuals with Lynch syndrome. Results Among the 40 patients, 21 had been diagnosed with cancer (affected group), while 19 were cancer-free and undergoing routine surveillance (non-affected group). The distribution of MMR gene mutations was 40% MSH2, 25% MSH6, 25% PMS2, and 15% MLH1. In the non-affected group, the median age was 38 years, with a BMI of 21.4. Surveillance identified one urothelial carcinoma and one case of endometrial hyperplasia. In the affected group, the mean age was 55.2 years, and the BMI was 24.7. Twenty-three gynecological cancers were diagnosed, of which 52% were endometrial, 26% ovarian, and 18% breast cancers. 61.1% of tumors were MSI-positive, and 33.3% of patients received immunotherapy. Conclusion A holistic, multidisciplinary approach is essential for the management of LS patients in gynecological oncology. The structured consultation model developed at Charité facilitates personalized surveillance, risk-adapted prevention, and evidence-based therapy strategies. Future studies and clinical trials should further investigate screening protocols, therapeutic interventions, and the role of LS patients in targeted treatment approaches. This guideline serves as a preliminary framework and will be continuously adapted as new research emerges.

Obstacles in genetic testing for germline BRCA1/2 pathogenic mutations in patients with primary breast and ovarian cancer in Switzerland

Approximately 5-10% of breast and up to 25% of ovarian cancer cases are hereditary, predominantly associated with germline BRCA1/2 pathogenic variants. Identifying these mutations is essential for personalized treatment, prevention strategies, and cascade testing in families. However, integrating genetic testing into routine care faces substantial barriers globally and within Switzerland. This retrospective, quantitative study analyzed 209 patients treated for non-mucinous ovarian carcinoma or primary breast cancer at the Women's Cantonal Hospital, Lucerne (2017-2022). All patients met Swiss clinical (SAKK) criteria for genetic testing, and recommendations for counseling were documented. Data were collected via anonymized questionnaires evaluating demographics, counseling experiences, emotional responses, and testing barriers. Statistical analyses examined factors influencing counseling uptake, including timing, referral source, education, and informational resources. Out of 73 respondents (32.6% response rate), 70 questionnaires were analyzed. Acceptance of genetic counseling was 81.4%. Recommendations by gynecologists significantly enhanced uptake (p = 0.002), especially when provided postoperatively or at diagnosis (p = 0.011). Higher education levels (p = 0.009) and prior informational materials (p = 0.014) positively influenced acceptance. Emotional responses differed, with breast cancer patients reporting more fear, whereas ovarian cancer patients reported greater curiosity. Family involvement supported patient engagement, while perceptions of minimal personal benefit and family disinterest were common reasons for declining. Timely, well-communicated recommendations and informational resources significantly improve genetic counseling uptake among breast and ovarian cancer patients. Addressing systemic and patient-specific barriers will enhance equitable access, optimize targeted therapies and preventive strategies, and should be supported by national registries, qualitative research, and digital integration.

Efficacy and safety of pressurized intraperitoneal aerosol chemotherapy (PIPAC) in ovarian cancer: a systematic review of current evidence

Abstract Background PIPAC is a recent approach for intraperitoneal chemotherapy with promising results for patients with peritoneal carcinomatosis. A systematic review was conducted to assess current evidence on the efficacy and outcomes of PIPAC in patients affected by ovarian cancer. Methods The study adhered to the PRISMA guidelines. PubMed, Google Scholar and ClinicalTrials.gov were searched up to December 2023. Studies reporting data on patients with OC treated with PIPAC were included in the qualitative analysis. Results Twenty-one studies and six clinical trials with 932 patients who underwent PIPAC treatment were identified. The reported first access failure was 4.9%. 89.8% of patients underwent one, 60.7% two and 40% received three or more PIPAC cycles. Pathological tumour response was objectivated in 13 studies. Intra-operative complications were reported in 11% of women and post-operative events in 11.5% with a 0.82% of procedure-related mortality. Quality of life scores have been consistently stable or improved during the treatment time. The percentage of OC patients who became amenable for cytoreductive surgery due to the good response after PIPAC treatment for palliative purposes is reported to be 2.3%. Conclusion The results showed that PIPAC is safe and effective for palliative purposes, with a good pathological tumour response and quality of life. Future prospective studies would be needed to explore the role of this treatment in different stages of the disease, investigating a paradigm shift towards the use of PIPAC with curative intent for women who are not eligible for primary cytoreductive surgery. Graphical abstract

The prognostic importance of features of myometrial invasion in endometrial endometrioid carcinoma

Abstract Purpose The depth of myometrial invasion (MI) is known to have a prognostic value in endometrial carcinoma (EC), and the FIGO 50% cutoff is widely accepted; however, recent studies have suggested other measurements such as the absolute depth of invasion and tumor-free distance (TFD) from the serosal surface to also be predictive. The aim of this study was to assess the association between the FIGO cutoff and other measures with overall survival and disease-free survival of patients. Methods This is a retrospective analysis of a cohort of 248 women diagnosed with stage I endometrioid endometrial carcinoma, treated at Soroka University Medical Center between 2006 and 2020. Clinical and pathological data were collected and analyzed. ROC analysis was used to define the best cutoffs in all three categories (MI, absolute depth and TDF). Survival analyses were then conducted using Kaplan–Meier curves, log-rank tests, and Cox proportional hazards regression. Results Absolute myometrial invasion (MI) to the depth of 1 cm significantly predicted overall survival (log-rank, p  = 0.009) in univariate analysis; however, this significance was not maintained in multivariate analysis. Additionally, a 33% MI cutoff demonstrated potential for better outcome prediction as compared to the commonly used 50% MI threshold, though it did not reach statistical significance. Tumor-free distance (TFD) from the serosal surface was not significantly associated with outcome. Conclusions MI depth of more than 1 cm may serve as a meaningful prognostic indicator. Additionally, a cutoff of 33% MI probably has a better prognostic value than the current 50% cutoff. These findings show a promising direction for future research, emphasizing the need for larger cohorts and multicenter studies to confirm our findings.

Evaluation of adnexal masses with ultrasonographic parameters and magnetic resonance imaging

Abstract Purpose Adnexal masses (AMs) are commonly seen gynecological problems. Most of the AMs of women in reproductive period are physiologic. A rare but lethal cause of AMs is ovarian cancer. It is important to distinguish benign and malignant AMs. In this study, two scoring systems named “Evaluation of Different Neoplasms in Adnexa (ADNEX)” model and “Ovarian-Adnexal Reporting Data System MR (O-RADS MR)” were examined in terms of diagnostic performance in distinguishing benign or malignant AMs. Methods Patients undergone surgery due to AMs were involved in this retrospective study. ADNEX risk model scores and MRI results of patients were re-evaluated for calculating O-RADS MRI scores. Results 284 patients enrolled in this study. ADNEX risk model had a 93.8% (95% CI: 90.9–96.7%) of area under the ROC curve (AUC) for malignancy risk ( p  &lt; 0.001). O-RADS risk model had a 95.7% (95% CI: 92.8–98.6) of AUC ( p  &lt; 0.001). When cut-off value was set as 42%, sensitivity and specificity of ADNEX risk model were 87% and 88.6, respectively. Sensitivity and specificity of O-RADS MRI risk scoring system were 93.8% and 93.2 when cut-off value was set as ≥ 4, respectively. AUC values of ADNEX risk model and O-RADS MRI scores were not significantly different in terms of differentiating between benign and malignant cases ( p  = 0.218). Conclusion ADNEX risk model and O-RADS MRI score are successful in terms of identifying benign and malign cases for evaluation of AMs. There was no significant difference in the ability of these two methods to distinguish benign and malignant cases.

Evaluation of pelvic floor muscle function (PFMF) in cervical cancer patients with Querleu–Morrow type C hysterectomy: a multicenter study

To evaluate the pelvic floor muscle function (PFMF) of cervical cancer patients after type QM-C hysterectomy and to explore the relationship between decreased PFMF and related factors. This was a multi-centered retrospective cohort study. 181 cervical cancer patients who underwent type QM-C hysterectomy were enrolled from 9 tertiary hospitals. Strength of PFMF were measured using neuromuscular apparatus (Phenix U8, French). Risk factors contributing to decreased PFMF were analyzed by univariate and multivariate ordinal polytomous logistic regression. Totally 181 patients were investigated in this study. 0-3 level of type I muscle fibre strength (MFSI) was 52.6% (95/181), 0-3 level of type IIA muscle fibre strength (MFSIIA) was 50% (91/181). Subjective stress urinary incontinence was 46% (84/181), urinary retention was 27.3% (50/181), dyschezia was 41.5% (75/181), fecal incontinence was 9% (18/181). ① MFSI: Multivariate ordinal polytomous logistic regression shows that the follow-up time (p < 0.05), chemotherapy and radiotherapy (p = 0.038) are independent risk factors of MFSI's reduction after type QM-C hysterectomy. ② MFSIIA: multivariate ordinal polytomous logistic regression shows that the follow-up time (p < 0.05) are independent risk factors of MFSIIA's reduction after type QM-C hysterectomy. The pelvic floor muscle strength (PFMS) increased after 9 months than in 9 months after operation, which showed that the PFMS could be recovered after operation. We advocate for more attention and emphasis on the PFMF of Chinese female patients with cervical cancer postoperation. PFMF after QM-C hysterectomy has not been analyzed by current study. The contribution is that patients with radical hysterectomy should do pelvic floor rehabilitation exercises in 3 months after operation. Clinical Trails NCT number of this study is 02492542.

Cervical injection as an alternative to the utero-ovarian ligament for mapping pelvic sentinel lymph node in early-stage ovarian cancer

Abstract Purpose In early-stage ovarian cancer, sentinel lymph node (SLN) mapping using double injection into the utero-ovarian and infundibulo-pelvic ligaments has been postulated. Cervical injection, commonly used in other gynaecologic tumors, may provide a simpler alternative to utero-ovarian injection for pelvic-SLN detection. This study aims to demonstrate whether cervical and utero-ovarian injections drain to the same pelvic SLN using different tracers for each injection site: technetium-99m (99mTc) at cervix and indocyanine green into the utero-ovarian ligament. Methods This prospective trial enrolled endometrial cancer patients scheduled for SLN biopsy from July 2023 to May 2024. Each hemipelvis was considered a case. 99mTc was injected at the cervix preoperatively. If 99mTc migration occurred, indocyanine green was injected into the utero-ovarian ligament intraoperatively. Concordance of migration was determined in those hemipelvis with both 99mTc-cervical and indocyanine green utero-ovarian migration. Results Seventeen patients (34 hemipelvis) were included. Migration from both injection sites occurred in 17 hemipelvis, identifying the same pelvic-SLN in all cases, being the concordance rate of 100%. Migration of 99mTc or indocyanine green from cervical injection was detected in 91.2% (95% CI 81.6–100%), whereas migration of indocyanine green injection from the utero-ovarian ligament was detected in 73.9% (95% CI 56–91.9%); these detection rates were not significantly different (p = 0.077). Conclusions Lymphatic migration from the cervix to the pelvis seems to be comparable to the migration from the utero-ovarian ligament to the pelvis, with both pathways converging at the same SLN.

Surgical parameters affecting procedure duration of hysteroscopic fibroid resection: results of a retrospective longitudinal study

To identify and analyze the main surgical parameters affecting the operative time of hysteroscopic fibroid resection. This retrospective observational study included 65 cases of outpatient hysteroscopic fibroid resection performed between March 2021 and May 2023 in outpatient office setting. Patients aged 18-50 with various indications such as infertility, recurrent pregnancy loss, or abnormal uterine bleeding (AUB) were included. The operative time, fibroid size, FIGO classification, and fibroid localization were recorded and analyzed using ANOVA, Chi-square test, and linear regression models. The average operative duration for all surgeries was 557.41 (± 449.52) s. A significant correlation between fibroid size and operative time was found in FIGO 0 (p = 0.0003) and FIGO 1 (p < 0.0001) subgroups, with weaker correlation in FIGO II (p = 0.039). FIGO I surgeries took significantly longer than FIGO 0 (p = 0.044), and fundal fibroids were associated with longer operative times compared to posterior fibroids (p = 0.0329). The size and FIGO classification of fibroids significantly influence operative time during hysteroscopic resection. Smaller and more accessible fibroids (FIGO 0 and 1) are resected faster than those embedded deeper in the uterine wall (FIGO 2). Detailed preoperative evaluation of fibroid characteristics can better predict operative time, aiding in patient preparation and optimized analgesia and perioperative planning as well as optimizing the use of operating theater. Further studies with larger sample sizes are recommended to validate these findings and explore additional influencing factors.

Association of ovarian teratoma with anti-N-methyl-D-aspartate receptor encephalitis: a case report and narrative review

Abstract Background Anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis is a potentially life-threatening autoimmune disorder which is strongly associated with ovarian teratomas in young female patients. The primary aim is to highlight the importance of considering NMDAR encephalitis in the differential diagnosis of young female patients presenting with acute or subacute neuropsychiatric symptoms, especially when accompanied by ovarian teratomas. Case description This case report and literature review detail the presentation, diagnosis, and treatment of a 35-year-old G4P3 Indigenous woman who initially presented with neuropsychiatric symptoms and fever, having a history of extensive drug and alcohol use. Misdiagnosed initially, the patient's lack of response to standard treatments led to further investigations, revealing paraneoplastic anti-NMDAR encephalitis secondary to a left ovarian teratoma. The report examines the treatment regimen followed, including prednisolone, intravenous immunoglobulin, rituximab injections, and laparoscopic bilateral salpingo-oophorectomy. Conclusions This case underscores the critical need for increased clinical vigilance for anti-NMDAR encephalitis in patients, particularly young females, presenting with neuropsychiatric symptoms and potential ovarian teratomas. The literature review accompanying the case report provides valuable insights into the presentation, diagnosis, and management of this complex condition. Lastly, this study emphasised the diagnostic challenges inherent in paraneoplastic neuropsychiatric syndromes, advocating for a multidisciplinary approach in similar clinical scenarios.

Predictors of quality of life and resilience in patients with ovarian cancer during the COVID-19 pandemic: a cross-sectional study

Abstract Purpose The aim of this cross-sectional study was to investigate the psychosocial burdens of patients with ovarian cancer during the COVID-19 pandemic. Methods Ovarian cancer patients answered a quantitative survey assessing their resilience (BRS) and quality of life (FACT-G7) as well as clinical (first- vs. ≥ second-line treatment), demographic (age &lt; 65 vs. ≥ 65 years) and COVID-19 pandemic-related psychosocial impairment, i.e. anxiety (GAD7); depression (PHQ2); global physical, mental, and social health (PROMIS items). Analyses of variance were applied to compare psychological impairment between patients on first- vs. ≥ second-line treatment and between patients aged &lt; vs. ≥ 65 years at start of treatment. Multiple linear regression analyses were performed to evaluate predictors of patients' resilience and quality of life based on demographic, clinical, and psychosocial variables. Results Most of the 93 patients rated their physical and mental health, and satisfaction with social activities as good. Eighty-seven (91.4%) were somewhat or very concerned about the pandemic. Patients on first-line therapy reported a better quality of life ( p  = 0.03) and better general health ( p  = 0.014) than those on at least second-line therapy. Patients &lt; 65 years old reported significantly more concern about the pandemic than older patients ( p  = 0.008). Predictors of resilience were severity of anxiety (GAD-7) and mental health. Predictors of quality of life were general health, severity of depression (PHQ-2), and type of therapy. Conclusions Patients in first line of treatment and younger patients could benefit from support in coping with pandemic-related burdens, meaning that attention should be paid to potential psychological distress, which should be treated alongside the cancer.

The prognostic influence of hospital type, method of first histological confirmation and time to chemotherapy in patients with advanced primary ovarian cancer

Abstract Purpose Ovarian cancer is the fifth most common cancer in women and the leading cause of death of all gynecological malignancies. Prognosis is determined by optimal surgical outcome (macroscopic complete resection) most commonly achieved in tertiary hospitals. We investigated whether tertiary versus non-tertiary hospital as the location of an initial diagnostic intervention for histological confirmation before cytoreductive surgery versus immediate primary debulking surgery impacts outcome in patients with advanced ovarian cancer. Methods We analyzed 115 patients who underwent cytoreductive surgery at a German tertiary center: 60 patients underwent primary debulking surgery (PDS) and 55 patients had a diagnostic intervention for histological confirmation before debulking surgery (PHC). Results Although there was no prognostic difference between the two subgroups, the median time to chemotherapy was longer in the PHC group (46 days) compared to the PDS group (26 days; p &lt; 0.0001), equally seen comparing non-tertiary versus tertiary PHC groups (p: 0.0001), its impact confirmed in a multivariate analysis (PFS: HR: 1.03, 95%CI: 1.01–1.05, p: 0.007; OS: HR: 1.04, 95%CI: 1.02 –1.06, p: &lt; 0.001) of the PHC group only. In total, 9/10 patients with port-site metastases after diagnostic laparoscopy were initially treated at non-tertiary hospitals, resulting in a lower PFS compared to patients without port-site metastases after laparoscopy (HR 0.21, 95%CI 0.06–0.733, p: 0.014). Conclusions In conclusion, patients with ovarian cancer undergoing treatment solely at a tertiary center have some clinical benefits and improved outcome, given the shorter time to chemotherapy and potential impact of port-site metastases. This supports centralization of oncological treatment.

Prognostic impact of microscopic residual disease after neoadjuvant chemotherapy in patients undergoing interval debulking surgery for advanced ovarian cancer

Abstract Purpose To determine the prognostic impact of microscopic residual disease after neoadjuvant chemotherapy (NACT) in patients undergoing interval debulking surgery (IDS) for advanced epithelial ovarian cancer (AEOC). Methods Patients affected by FIGO stage IIIC–IV ovarian cancer undergoing IDS between October 2010 and April 2016 were selected. Progression-free survival (PFS) and overall survival (OS) were estimated using the Kaplan–Meier analysis. Results In total, 98 patients were identified. Four patients (4.1%) were considered inoperable. Overall, 67 patients (out of 94; 71.3%) had macroscopic disease, equating Chemotherapy Response Score (CRS) 1 and 2, 7 (7.4%) had microscopic residuals, equating CRS3, rare CRS2, while 20 (21.3%) had both microscopic and macroscopic disease. Median OS and PFS were, respectively, 44 and 14 months in patients with no macroscopic residual disease (RD = 0) compared to 25 and 6 months, in patients with RD &gt; 0 (OS: p = 0.001; PFS: p = 0.002). The median PFS was 9 months compared to 14 months for patients with more or less than 3 areas of microscopic disease at final pathologic evaluation (p = 0.04). The serum Ca125 dosage after NACT was higher in patients with RD &gt; 0 compared to those without residue (986.31 ± 2240.7 µg/mL vs 215.72 ± 349.5 µg/mL; p = 0.01). Conclusion Even in the absence of macroscopic disease after NACT, the persistence of microscopic residuals predicts a poorer prognosis among AEOC patients undergoing IDS, with a trend towards worse PFS for patients with more than three affected areas. Removing all fibrotic residuals eventually hiding microscopic disease during IDS represents the key to improving the prognosis of these patients.

Real-life clinical benefit of oral metronomic cyclophosphamide administration in elderly and heavily pretreated epithelial ovarian cancer patients

Abstract Purpose Oral metronomic cyclophosphamide (OMC) implicates the daily administration of low doses of chemotherapy. Its antitumor activity combined with an oral administration route and a good toxicity profile makes OMC an attractive option for heavily pretreated patients. We retrospectively evaluated OMC’s clinical benefit and objective response in recurrent ovarian cancer patients. Methods This is a retrospective observational study involving patients treated with OMC (50 mg daily) from 2017 to 2022 at the Academic Division Gynaecology, Mauriziano Hospital, Torino, Italy. Clinical benefit assessment included CA125 response, radiological response, and reported symptomatic improvement. Toxicities were reported using Common Terminology Criteria for Adverse Events version 5.0. Results Thirty-eight patients (average age 72, range 49–88) were included. 90% had FIGO stage III/IV at diagnosis and 64% underwent ≥ 3 previous lines of chemotherapy. Before OMC, 79% had ECOG 1 or 2. 8.6% of patients had a partial response (PR), and 40% a stable disease (SD). Median duration of response was 7.4 months. After 3 months on OMC, 51% experienced symptom improvement, and 53.3% experienced Ca125 reduction or stabilization. 66.7% of patients older than 75 responded to treatment; in 40% of cases, responses lasted ≥ 6 months (p = 0.08). No G3-4 hematological toxicities occurred. Nausea and fatigue G1–G2 were reported in 5 (13%) and 13 (34%) cases, respectively. Conclusion OMC is a feasible therapeutic option for recurrent ovarian cancer, providing satisfying clinical responses with a good toxicity profile, even in elderly and heavily pretreated patients with a suboptimal performance status.

Could uterine conservation be an option in presumed early-stage epithelial ovarian cancer?

In early-stage epithelial ovarian cancer (EOC), patients usually undergo a hysterectomy. However, in fertility sparing surgery (FSS), carefully selected patients could conserve their uterus. The aim of our study was to evaluate the incidence and epidemiologic characteristics associated with uterine involvement in patients with early-stage EOC, outside of FSS. We conducted a retrospective, monocentric, study from 2003 to 2019 and included all patients with a presumed early-stage EOC (FIGO I) who underwent a hysterectomy. The incidence of uterine involvement, predictive factors of uterine involvement, and the impact of uterine involvement on survival (recurrence-free survival and overall survival) were analyzed. Eighty-five patients had an early-stage EOC. Of these, six had an uterine involvement (7%). The populations of patients with or without uterine involvement did not differ except for CA 125 at diagnosis (136 ± 138 versus 356 ± 723, p = 0.04, respectively). No patient or tumor characteristics were predictive of uterine involvement. Uterine involvement was not associated with recurrence-free survival (HR = 1.26, IC95% 0.36-4.4, p = 0.72) or overall survival (HR = 0.7, IC95% 0.1-6.1, p = 0.77). Due to the small size of our sample, no conclusion can be drawn, yet it could be hypothesized that, for selected patients, a systematic hysterectomy could be discussed, notably in restaging surgery.

Association between BMI and oncologic outcomes in epithelial ovarian cancer: a predictors-matched case-control study

Abstract Objective We aimed to study the association between obesity and survival in ovarian cancer (OC) patients, accounting for confounders as disease stage, histology, and comorbidities. Methods Retrospective matched case-control study of consecutive patients, with epithelial OC. Obese (body mass index [BMI] ≥ 35 kg m−2) patients were matched in a 1:4 ratio with patients having lower BMIs (BMI &lt; 35 kg m−2) based on disease stage, cytoreduction state, tumor histology and ASA score. We compared the 3-year and total recurrence-free survival and overall survival through Kaplan–Meier survival curves and Cox proportional hazards. Results Overall, 153 consecutive patients were included, of whom 32 (20.9%) had a BMI ≥ 35. and 121 a BMI &lt; 35. The median follow-up time was 39 months (interquartile range 18–67). Both study groups were similar in multiple prognostic factors, including American Society of Anesthesiologists physical status, completion of cytoreduction, histology and stage of disease (p = 0.981, p = 0.992, p = 0.740 and p = 0.984, respectively). Ninety-five (62.1%) patients underwent robotic surgery and conversion rate from robotic to laparotomy was similar in both groups 2 (6.3%) in obese group vs. 6 (5.0%) in lower BMI patients, p = 0.673. During the follow-up time, the rate of recurrence was similar in both groups; 21 (65.6%) in obese group vs. 68 (57.1%), p = 0.387 and the rate of death events was similar; 16 (50.0%) in obese group vs. 49 (40.5%), p = 0.333). The 3-year OS was higher in the obese group (log rank p = 0.042) but the 3-year RFS was similar in both groups (log rank p = 0.556). Median total OS was similar in both groups 62 months (95% confidence interval 25–98 months) in obese vs. 67 months (95% confidence interval 15–118) in the lower BMI group, log rank p = 0.822. Median RFS was similar in both groups; 61 months (95% confidence interval 47–74) in obese, vs. 54 (95% confidence interval 43–64), log rank p = 0.842. In Cox regression analysis for OS, including obesity, age, laparotomy and neoadjuvant treatment – only neoadjuvant treatment was independently associated with longer OS: odds ratio 1.82 (95% confidence interval 1.09–3.05) and longer RFS: odds ratio 2.16 (95% confidence interval 1.37–3.41). Conclusions In the present study on consecutive cases of ovarian cancer, obesity did not seem to be associated with outcome, except for an apparent improved 3-year survival that faded away thereafter.

Predictors of significant distress in cervical cancer patients: a cross sectional study

Abstract Purpose This cross-sectional study aims to investigate parameters that predict relevant levels of distress in women in a perioperative setting undergoing treatment for cervical cancer. Materials and methods Data from 495 patients with cervical cancer that were treated at the university hospital Aachen between 2010 and 2022 were analysed based on their respective National Comprehensive Cancer Network (NCCN) Distress Thermometer score (DT) and Problem List (PL) and their clinical history. 105 patients were enrolled in the study. 18 medical and demographic variables were analysed using multivariate logistic regression. Results Three variables contributed significantly to the prediction of a DT score ≥ 5. Significant distress was defined as a DT score of ≥ 5, which was observed in 70.5% of the participants (mean: 5.58 ± 2.892). Women who chose to receive psycho-oncological counselling were more likely to have a DT score ≥ 5 (Odds Ratio(OR) = 3.323; Confidence Interval (CI95%): 1.241–8.900; p-value: 0.017). In addition, women who did not receive chemoradiation had significantly higher DT scores (OR = 3.807; CI 95%:1.185–12.236; p-value: 0.025), as did women whose Distress Thermometer was assessed in the first month after their initial diagnosis (OR = 3.967; CI 95%:1.167–13.486; p-value: 0.027). Conclusion Increased distress in women with cervical cancer is common especially in the first month after diagnosis, in patients who do not receive chemoradiation and in patients who seek psycho-oncological counselling. Surgical factors do not play a major role in patient distress.

Health-related quality of life after robotic surgery for endometrial cancer: a prospective longitudinal one-year follow-up study

AbstractPurposeThis study aimed to explore how patients treated for endometrial cancer (EC) with robotic surgery are affected in symptoms of anxiety and depression and HRQoL in the long term.MethodsWomen scheduled for primary robotic surgery for EC were included (n = 64), in this single-center study. Socioeconomic variables were obtained at baseline. The European Organization for Research and Treatment of Cancers Quality of Life Questionnaire Core 30 (QLQ-C30), its module for EC (EN24), the Generalized Anxiety Disorder Scale (GAD-7), and the Patient Health Questionnaire Depression Scale (PHQ-9) were followed prospectively from baseline to 2 weeks, 3 months and 1 year postoperatively.ResultsThe number of patients scoring above the clinical threshold for anxiety decreased from 17 (27.0%) at baseline to 4 (7.0%) at 2 weeks (p = 0.012). Depressive symptoms were reported in 20% of patients at baseline and did not change significantly during the one-year follow-up (p = 0.58). A significant decrease in Global health status was seen at 2 weeks (from 69.8 to 62.7;p = 0.048), with return to baseline levels after 3 months (68.5;p = 0.32) and stable at 1 year. Unemployment, low income, and adjuvant therapy correlated with lower Global health status at 3 months.ConclusionThe significant proportion of patients with anxiety symptoms preoperatively reduced prompt after surgery, while the proportion with depression remained constant, indicating that the primary treatment has no long-term negative effect on patients’ mental health. At 3 months, there is no obvious remaining negative impact on patients’ HRQoL, and these results are consistent after 1 year.

New online dynamic nomograms to predict recurrence-free and overall survival after resection of endometrial cancer: a single-institution retrospective cohort study

Abstract Purpose The significant global burden of endometrial cancer (EC) and the challenges associated with predicting EC recurrence indicate the need for a dynamic prediction model. This study aimed to propose nomograms based on clinicopathological variables to predict recurrence-free survival (RFS) and overall survival (OS) after surgical resection for EC. Methods This single-institution retrospective cohort study included patients who underwent surgical resection for EC. Web-based nomograms were developed to predict RFS and OS following resection for EC, and their discriminative and calibration abilities were assessed. Results This study included 289 patients (median age, 56 years). At a median follow-up of 51.1 (range, 4.1–128.3) months, 13.5% (39/289) of patients showed relapse or died, and 10.7% (31/289) had non-endometrioid tumors (median size: 2.8 cm). Positive peritoneal cytology result (hazard ratio [HR], 35.06; 95% confidence interval [CI], 1.12–1095.64; P = 0.0428), age-adjusted Charlson comorbidity index (AACCI) (HR, 52.08; 95% CI, 12.35–219.61; P &lt; 0.001), and FIGO (Federation of Gynecology and Obstetrics) stage IV (HR, 138.33; 95% CI, 17.38–1101.05; P &lt; 0.001) were predictors of RFS. Similarly, depth of myometrial invasion ≥ 1/2 (HR, 1; 95% CI, 0.46–2.19; P = 0.995), AACCI (HR, 93.63; 95% CI, 14.87–589.44; P &lt; 0.001), and FIGO stage IV (HR, 608.26; 95% CI, 73.41–5039.66; P &lt; 0.001) were predictors of OS. The nomograms showed good predictive capability, positive discriminative ability, and calibration (RFS: 0.895 and OS: 0.891). Conclusion The nomograms performed well in internal validation when patients were stratified into prognostic groups, offering a personalized approach for risk stratification and treatment decision-making.

Laparoscopic surgery for endometrial cancer is oncologically safe and improves hospital stay duration: a retrospective single-center study over a 16-year period

Abstract Objective To investigate changes in surgical procedures and patient outcomes of patients diagnosed with endometrial cancer (EC) at a German university hospital between 1998 and 2014. Methods A monocentric, retrospective review was conducted to identify patients diagnosed and treated with EC during the aforementioned period at the Department of Gynecology and Obstetrics at the University Hospital Kiel, Germany. Results 303 patients were identified. Patient demographics, risk factors, histological subtypes and stages of EC remained consistent over time. The most common surgical procedure was total abdominal hysterectomy (TAH) (81.9%). In 2011, the institution carried out its first total laparoscopic hysterectomy (TLH) for EC, resulting in a significant increase in laparoscopic surgical procedures (2011–2014: N = 70; TAH 44.2%; TLH 51.4%). Although the total number of lymph node stagings remained consistent over time, there was a significant increase in the performance of simultaneous pelvic and para-aortic lymphonodectomy (LNE) compared to pelvic LNE alone (2.6 in 2001–2005 vs. 18.0% in 2011–2014, p ≤ 0.001). The duration of hospital stays significantly decreased over time, with a mean of 20.9 days in the first and 8.5 days in the last period. When comparing surgical procedures, TLHs resulted in significantly shorter postoperative stays with an average of 6.58 vs. 13.92 days for TAH. The surgical procedure performed did not affect 5-year overall survival rates in this study (84.9% for TAH and 85.3% for TLH, p = 0.85). Conclusions Our retrospective single-center study demonstrates that laparoscopic surgery for endometrial cancer is oncologically safe and shortens hospital stays.

Real-world prevalence of microsatellite instability testing and related status in women with advanced endometrial cancer in Europe

Abstract Purpose To assess the real-world prevalence of microsatellite instability (MSI)/mismatch repair (MMR) testing and related tumor status in recurrent/advanced endometrial cancer patients in Europe. Methods Data were from two multi-center, retrospective patient chart review studies conducted in the United Kingdom, Germany, Italy, France and Spain: The Endometrial Cancer Health Outcomes-Europe-First-Line (ECHO-EU-1L) study and the ECHO-EU-Second-Line (ECHO-EU-2L) study. ECHO-EU-1L included recurrent/advanced endometrial cancer patients who received first-line systemic therapy between 1/JUN/2016 and 31/MAR/2020 after recurrent/advanced diagnosis. ECHO-EU-2L included patients with recurrent/advanced endometrial cancer who progressed between 1/JUN/2016 and 30/JUN/2019 following prior first-line systemic therapy. Data collected included patient demographics, MSI/MMR tumor testing and results, and clinical/treatment characteristics. Results ECHO-EU-1L included 242 first-line patients and ECHO-EU-2L included 475 s-line patients. For all patients, median age at recurrent/advanced diagnosis was 69 years, roughly half had endometrioid carcinoma histology and over 75% had Stage IIIB-IV disease at initial diagnosis. The prevalence of MSI/MMR testing in the first-line and second-line cohorts was similar (36.4 and 34.9%, respectively). Among those tested, a majority had non-MSI-high/MMR proficient tumors (80.7 and 74.7% among first- and second-line patients, respectively). About 15% had MSI-high/MMR deficient tumors in both cohorts, and a few patients had discordant results (3.4 and 10.8% among first- and second-line patients, respectively). Conclusion Prior to the approvals of biomarker-directed therapies for recurrent/advanced endometrial cancer patients in Europe, there were low MSI/MMR testing rates for these patients of just over one-third. Given the availability of biomarker-directed therapies, increased MSI/MMR testing may help inform treatment decisions for recurrent/advanced endometrial cancer patients in Europe.

Distinct endometriosis involvement confers divergent oncologic outcomes in ovarian clear cell carcinoma

To evaluate the clinicopathologic characteristics and survival outcomes of ovarian clear cell carcinoma (OCCC) patients with different endometriosis statuses. This retrospective study included OCCC patients diagnosed between 2012 and 2021, classified into three groups based on the Sampson and Scott criteria: Without (no endometriosis), Arising (OCCC arising from endometriosis), and Coexisting (OCCC coexisting with endometriosis). Clinical and pathological characteristics were compared across groups, and survival outcomes were analyzed using Kaplan-Meier methods. Prognostic factors for progression-free survival (PFS) and overall survival (OS) were identified through univariate and multivariate analyses. Among 242 patients, 53.7% were in the Without group, 29.3% in the Arising group, and 16.9% in the Coexisting group. The Arising group had the highest prevalence of early FIGO stage disease (91.6%) compared to the Coexisting (75.6%, p = 0.041) and Without (67.7%, p = 0.000) groups. Lymph-node metastasis was significantly lower in the Arising group (2.8%) than in the Coexisting (19.5%, p = 0.010) and Without (10%, p = 0.011) groups. Notably, the Arising group demonstrated unique atypical endometriosis features. In univariate analysis, the presence of endometriosis (either arising from or coexisting with endometriosis) was associated with improved PFS (p = 0.004 and p = 0.009, respectively); however, multivariate analysis confirms only coexisting with endometriosis as an independent factor (HR: 0.11, 95% CI: 0.01-0.84). For OS, the Arising group demonstrated the most significant benefit, with a 5-year OS of 92.4% compared to the Coexisting group (83.9%, p = 0.293) and the Without group (62.6%, p = 0.023). Multivariate analysis identified only FIGO stage (HR: 5.89, 95% CI: 2.06-16.82) as an independent prognostic factor for OS, while endometriosis did not reach statistical significance (HR: 0.62, 95% CI: 0.26-1.53). Classifying OCCC with endometriosis statuses reveals distinct prognostic patterns. Coexisting with endometriosis positively impacts PFS, while the Arising subgroup shows the most significant OS benefit but may be confounded with other factors.

Peritoneal mesometrial resection with lymphadenectomy following prior hysterectomy in intermediate/high-risk endometrial cancer: feasibility and safety

Abstract Objective Peritoneal mesometrial resection (PMMR) plus targeted compartmental lymphadenectomy (TCL) aims at removal of the locoregional cancer field in endometrial cancer (EC). Optimal locoregional control without adjuvant radiotherapy should be achieved concomitantly sparing systematic lymphadenectomy (LNE) for most of the patients. However, intermediate/high-risk EC is often definitely diagnosed postoperatively in simple hysterectomy specimen. Our aim was to evaluate feasibility and safety of a completing PMMR + TCL in patients following prior hysterectomy. Methods We evaluated data from 32 patients with intermediate/high-risk EC treated with PMMR + TCL or systematic pelvic and periaortic LNE following prior hysterectomy. Perioperative data on disease characteristics and morbidity were collected and patients were contacted for follow-up to determine the recurrence and survival status. Results We report data from 32 patients with a mean follow-up of 31.7 months. The recurrence rate was 12.5% (4/32) without any isolated locoregional recurrences. Only 21.9% of patients received adjuvant radiotherapy. Rates of intra- and postoperative complications were 6.3% and 18.8%, respectively. Conclusion Our data suggest that robotic PMMR can be performed following prior hysterectomy when previously unknown risk factors arise, albeit with a moderate increase in morbidity. Moreover, despite a relevant reduction of adjuvant radiotherapy, follow-up data suggest an excellent locoregional control even without adjuvant radiotherapy.

Radiotherapy improves stress urinary incontinence but impairs pelvic floor function in endometrial cancer patients: a prospective cohort study

Abstract Purpose Investigating the impact of radiotherapy on urinary incontinence and pelvic floor dysfunction in endometrial cancer patients. Method A comparative study was conducted between endometrial cancer patients who underwent radiotherapy and those who did not receive adjuvant therapy. Patients were assessed during their first follow-up visit at third month post-radiotherapy or post-surgery. Demographic data and physical examinations were conducted, along with the administration of validated questionnaires. Turkish validated Incontinence Severity Index (ISI), Incontinence Impact Questionairre-7 (IIQ-7) and 20 ıtem Pelvic Floor Dysfunction Index (PFDI-20) were applied to the all patients. Results The study comprised 37 patients in the non-radiotherapy group and 41 patients in the radiotherapy group. Comparable demographics were observed between the two groups. Vaginal length was notably longer in the non-radiotherapy group, and the Q-tip test angle was significantly greater in this group. A higher incidence of stress urinary incontinence and higher scores on the Incontinence Severity Index were noted in the non-radiotherapy group. Conversely, the radiotherapy group exhibited significantly higher scores on the Pelvic Floor Dysfunction Index components and total score. Urogenital Distress Inventory scores were similar between the groups. Conclusion Radiotherapy showed mixed effects on pelvic floor function in endometrial cancer patients. While it potentially improved stress urinary incontinence, it was associated with unfavorable outcomes in overall pelvic floor dysfunction.

Association of body mass index with pathologic agreement of preoperative and postoperative tumor grade in endometrial cancer

Abstract Objective We aim to study association of BMI of EC patients, with the level of agreement between preoperative and postoperative tumor grade. Methods A retrospective study. We included patients with EC diagnosed in an outpatient clinic which had surgical staging as in our division. We categorized patients into BMI categories according to the World Health Organization; (BMI &lt; 18.5 kg/m2), (BMI 18.5–24.9 kg/m2), (BMI 25–29.9 kg/m2), (BMI 30–34.9 kg/m2), (BMI 35–39.9 kg/m2), and (BMI ≥ 40 kg/m2). We further dichotomized the study population for obesity, defined as BMI ≥ 30.0. We analyzed agreement between preoperative and postoperative tumor grade, stratified by patient’s BMI. Results Overall, 623 women met study inclusion criteria, with a median age of 64 [interquartile range (IQR) 57–72]. Among the study cohort, the median BMI was 30.7 [IQR 25.6–38.8], with 330 (53.0%) patients being obese. EC grade 1 was diagnosed preoperatively in 353 (56.7%), grade 3 in 148 (23.8%), and grade 2 in 122 (19.6%). Endometrioid histology was diagnosed in 463 (74.3%), serous in 78 (12.5%), mixed histotype in 51 (8.2%), clear cell in 20 (3.2%) and carcinosarcoma in 11 (1.8%). In 68.7% (n = 428), there was no change in postoperative grade, and in 24.9% (n = 155), there was upgrading of tumor, and in 6.4% (n = 40), there was a tumor downgrade. There were 3 (0.5%) cases in which no tumor was found on final pathology. The rate of no change was higher in preoperative grade 3 (89.9%) vs. grades 1 (63.5%) and grade 2 (58.2%), p &lt; .001). There was no difference in grading agreement when obese patients were compared to non-obese, p = .248. There was no difference in grading agreement when comparing the various BMI categories, with no change proportion ranging between 58.2% in BMI 30.0–34.9 mg/kg2 and 79.7% in BMI 35.0–39.9 mg/kg2, p = .104. ROC analysis of BMI as predictor of no-change yielded an area under the curve of 0.466 (95% confidence interval 0.418–0.515) with a maximal performance at a BMI of 33.8 mg/kg2. The agreement between preoperative and postoperative tumor grade among all patients was kappa = 0.517. The agreement did not differ when compared between obese patients (kappa = 0.456) and non-obese (kappa = 0.575). Conclusion Our study found no significant association between BMI and the agreement between preoperative and postoperative tumor grading in EC.

Segmented in vitro fertilization and frozen embryo transfer in levonorgestrel-releasing intrauterine device treated patients with endometrial cancer

Abstract Purpose To evaluate the efficacy of levonorgestrel-releasing intrauterine device (LNG-IUD) during controlled ovarian stimulation (COS) in patients with early-stage endometrioid endometrial cancer (EEC). Methods A retrospective study was conducted on patients with stage IA1 EEC who achieved complete response after fertility-sparing treatment from December 2018 to December 2021, with all the women who underwent COS having LNG-IUDs inserted in their uterine cavity. Results 16 patients were enrolled who underwent 26 COS cycles and average age was 33.19 ± 4.04 years. 12 patients had 19 subsequent frozen-thawed embryo transfer (FET) cycles. Among the other four patients, no embryos were obtained in 1 patient, 1 patient got pregnancy spontaneously with term delivery after COS, 1 patient relapsed before FET, and 1 patient did not receive embryo transfer for personal reason. Among 19 FET cycles, the clinical pregnancy and live birth rates in each ET cycle were 36.84% (7/19) and 26.32% (5/19), respectively. 7 clinical pregnancies resulted in 2 miscarriages (28.6%), and 5 live births (71.4%). Totally 6 patients achieved 7 live births, and the cumulative live birth rate was 37.5% (6/16). Three (18.75%) out of 16 patients relapsed after COS during the follow-up period (31.31 ± 15.89 months) and two of them were initially diagnosed with moderately differentiated EEC. Time interval from COS to relapse was 6.63,11.67 and 16.23 months, respectively. Conclusion The combination of LNG-IUD treatment and segmented IVF may be a viable treatment strategy to improve oncological and reproductive outcomes for patients with early-stage EEC.

Prognosis of patients with endometrial cancer or atypical endometrial hyperplasia after complete remission with fertility-sparing therapy

Abstract Purpose Although many patients with endometrial cancer (EC) or atypical endometrial hyperplasia (AEH) achieve complete remission (CR) after high-dose medroxyprogesterone acetate (MPA) treatment, no consensus has been reached on management after CR. Currently, patients receive estrogen-progestin maintenance therapy, but no recommendations exist regarding the duration of maintenance therapy or whether hysterectomy should be considered. This study aimed to provide insights into the management of EC/AEH after achieving CR. Methods We retrospectively investigated the prognosis of 50 patients with EC or AEH who achieved CR after MPA therapy. We assessed the association between disease recurrence and clinicopathological features and the pre- and post-operative histological diagnoses of patients who underwent hysterectomy. Results The median follow-up duration was 34 months (range: 1–179 months). Recurrence was observed in 17 patients. Among the clinical characteristics investigated, only the primary disease was significantly associated with disease recurrence; patients with EC had a higher risk of recurrence than those with AEH (p = 0.037). During the observation period, 27 patients attempted pregnancy, and 14 pregnancies resulted in delivery. Patients who gave birth had significantly longer relapse-free survivals than those who did not (p = 0.031). Further, 16 patients underwent hysterectomies, and AEH was detected postoperatively in 4 of 11 patients (36.4%) with no preoperative abnormalities. Conclusions We identified several clinical features of patients with EC and AEH after CR. Given the high probability of endometrial abnormalities detected postoperatively, hysterectomy may be considered for patients who no longer want children.

MSX1-expression during the different phases in healthy human endometrium

Abstract Purpose The human endometrium consists of different layers (basalis and functionalis) and undergoes different phases throughout the menstrual cycle. In a former paper, our research group was able to describe MSX1 as a positive prognosticator in endometrial carcinomas. The aim of this study was to examine the MSX1 expression in healthy endometrial tissue throughout the different phases to gain more insight on the mechanics of MSX-regulation in the female reproductive system. Materials and methods In this retrospective study, we investigated a total of 17 normal endometrial tissues (six during proliferative phase and five during early and six during late secretory phase). We used immunohistochemical staining and an immunoreactive score (IRS) to evaluate MSX1 expression. We also investigated correlations with other proteins, that have already been examined in our research group using the same patient collective. Results MSX1 is expressed in glandular cells during the proliferative phase and downregulated at early and late secretory phase ( p  = 0.011). Also, a positive correlation between MSX1 and the progesterone-receptor A (PR-A) (correlation coefficient (cc) = 0.0671; p  = 0.024), and the progesterone receptor B (PR-B) (cc = 0.0691; p  = 0.018) was found. A trend towards negative correlation was recognized between MSX1 and Inhibin Beta-C-expression in glandular cells (cc = − 0.583; p -value = 0.060). Conclusion MSX1 is known as a member of the muscle segment homeobox gene family. MSX1 is a p53-interacting protein and overexpression of homeobox MSX1 induced apoptosis of cancer cells. Here we show that MSX1 is expressed especially in the proliferative phase of glandular epithelial tissue of the normal endometrium. The found positive correlation between MSX1 and progesterone receptors A and B confirms the results of a previous study on cancer tissue by our research group. Because MSX1 is known to be downregulated by progesterone, the found correlation of MSX1 and both PR-A and -B may represent a direct regulation of the MSX1 gene by a PR-response element. Here further investigation would be of interest.

Awareness, knowledge and attitudes of human papillomavirus infection, screening and vaccination: a survey study in Greece

Abstract Purpose To evaluate the awareness and existing knowledge of a portion of the Greek population about prevention, screening, and HPV vaccination. Methods A questionnaire designed in Google forms has been distributed through social media between June 2021 and December 2021 in men and women aged &gt; 16 years old. Statistical analysis was performed using the SPSS 20.0 program. Inferential analysis was performed to evaluate differences in responses among men and women. Results We enrolled 2685 participants. Of those, 2285 were women, 386 were men, while 14 respondents chose not to respond to this question. Various age groups were detected with those aged between 26 and 30 years old being the predominant one. Participants with a higher education constituted 36.5% of the population. Most respondents were married (59.8%). In socioeconomic terms 75.5% of participants were employed whereas, monthly income ranged between 1000 and 1500 euros in the predominant group (36.8%). Only 40% of females and 3.9% of males were vaccinated against HPV. Adolescent immunization, acceptability rates reached 92.7% among female and 82.1% among male responders. Although, only a small proportion of the participants were not aware of the existence of HPV, 24.1% of males and 23.4% of females had the impression that condom use may provide absolute immunity to HPV and only 51.6% of males and 60.4% of females were aware about the high prevalence of HPV in the general population. Logistic regression analysis indicated that male participants as well as those aged &gt; 50 years and those choosing to reject vaccination had decreased knowledge of the basic pathophysiology of HPV infection, as well as knowledge related to the existence and use of HPV DNA as a screening tool and the existence and efficacy of HPV vaccination. Conclusion Our results indicate that although awareness of the existence of HPV infection is high in Greek general population, the actual perception of the pathophysiology of transmission and importance of HPV testing and vaccination is low. Targeting specific population groups is essential to help increase HPV coverage and screening.

Tubal ligation during cesarean delivery and future risk for ovarian cancer: a population-based cohort study

Data regarding the effect of post-partum bilateral tubal ligation (BTL) on future risk for ovarian cancer (OC) is lacking. In the current study, we aimed to evaluate the effect of BTL during cesarean delivery (CD) on the long-term risk for OC. A population-based cohort analysis of women above the age of 35 that underwent CD in their last delivery, comparing the long-term risk for OC between patients that had a Pomeroy excisional BTL and those that did not. OC diagnosis was pre-defined based on ICD-9 codes. Procedures occurred between the years 1991-2017. Kaplan-Meier survival curve was used to compare the cumulative incidence of OC over time and Cox proportional hazards model was constructed to control for confounders. During the study period 13,124 women met the inclusion criteria; 9438 (71.9%) of which had only CD and 3686 (28.1%) underwent CD with BTL. Despite the significantly higher incidence of maternal factors that might increase the long-term risk for OC in the BTL group (advanced maternal age, obesity, hypertensive diseases during pregnancy and diabetes mellitus), the cumulative incidence of OC cases was not significantly different between the two groups (Log-rank test p = 0.199). Likewise, when performing a Cox regression model controlling for maternal age, obesity, hypertensive diseases and diabetes, OC risk was not significantly different between the groups (adjusted HR 2.36, 95% CI 0.73-7.62; p = 0.149). Despite an increased incidence of known risk factors for OC, patients that underwent BTL during CD did not have increased long-term risk for OC.

The differential diagnostic value and clinical significance of serum HE4 in ovarian disease with elevated CA125

To determine the diagnostic value and clinical significance of serum HE4 levels in differentiating between benign and malignant ovarian disease in patients with elevated CA125 levels. The levels and positive expression rate of HE4 were compared between 371 patients with elevated CA125 levels and benign ovarian disease, and 132 patients with epithelial ovarian cancer to determine the diagnostic value of HE4. The level and positive expression rate of HE4 differed significantly between the benign and malignant groups, in that, there was no significant difference in HE4 expression between CA125 low- and high-level groups within the benign ovarian disease group, with levels of HE4 being in the normal range in both groups. However, the positive expression rates and levels of HE4 in the malignant group were significantly different between the serum CA125 low- and high-level groups. ROC curve analysis showed that optimal HE4 cutoff values for increased accuracy in diagnosis were 78.03 pmol/L and 119.70 pmol/L before and after menopause, respectively. Serum HE4 levels can potentially be used as a marker to differentiate between benign and malignant ovarian disease with elevated serum CA125 levels. The high specificity of HE4 was superior in identifying benign ovarian disease. We recommend increasing the cutoff values of HE4 in premenopausal patients and decreasing the cutoff values in postmenopausal patients for increased accuracy in the differential diagnosis of patients with elevated CA125 levels.

Advanced stage primary mucinous ovarian carcinoma. Where do we stand ?

To evaluate factors associated with survival of patients with advanced stage mucinous ovarian carcinoma (MOC) using a large multi-institutional database. Patients diagnosed between 2004 and 2014 with advanced stage (III-IV) MOC were identified within the National Cancer Database. Those without a personal history of another primary tumor who received cancer-directed surgery with a curative intent were selected for further analysis. Overall survival (OS) was evaluated with Kaplan-Meier curves, and compared with the log-rank test. Multivariate Cox analysis was performed to identify independent predictors of survival. A total of 1509 patients with a median age of 59 years (IQR 20) met the inclusion criteria: stage III (n = 1045, 69.3%) and stage IV disease (n = 464, 30.7%). Patients who received chemotherapy (n = 1065, 70.6%) had better OS compared to those who did not (n = 385, 25.5%), (median OS 15.44 vs 5.06 months, p < 0.001). The type of reporting facility (p = 0.65) and the year of diagnosis (p = 0.27) were not associated with OS. Presence of residual disease was strongly associated with OS (p < 0.001). After controlling for confounders, the administration of chemotherapy (HR 0.63, 95% CI 0.55, 0.72) was associated with better survival. Advanced stage MOC has an extremely poor prognosis. Patients who received chemotherapy had a small improvement in survival. Every effort to achieve complete gross resection should be performed. Given no improvement in survival outcomes over time, there is an eminent need for novel treatment options.

Prognostic factors and survival of patients with uterine sarcoma: a German unicenter analysis

Abstract Purpose Uterine sarcoma (US) as a histologically heterogeneous group of tumors is rare and associated with poor prognosis. Prognostic factors based on systematic data collection need to be identified to optimize patients’ treatment. Methods This unicenter, retrospective cohort study includes 57 patients treated at the University Hospital Freiburg, Germany between 1999 and 2017. Progression-free survival (PFS) and overall survival (OS) were calculated and visualized in Kaplan–Meier curves. Prognostic factors were identified using log-rank test and Cox regression. Results 44 Leiomyosarcoma (LMS), 7 low-grade endometrial stromal sarcoma (LG-ESS), 4 high-grade ESS and 2 undifferentiated US patients were identified. The median age at time of diagnosis was 51.0 years (range 18–83). The median follow-up time was 35 months. PFS for the total cohort was 14.0 (95%-Confidence-Interval (CI) 9.7–18.3) and OS 36.0 months (95%-CI 22.1–49.9). Tumor pathology was prognostically significant for OS with LG-ESS being the most favorable (mean OS 150.3 months). In the multivariate analysis, patients over 52 years showed a four times higher risk for tumor recurrence (hazard ratio (HR) 4.4; 95%-CI 1.5–12.9). Progesterone receptor negativity was associated with a two times higher risk for death (HR 2.8; 95%-CI 1.0–7.5). For LMS patients age ≥ 52 years (p = 0.04), clear surgical margins (p = 0.01), FIGO stage (p = 0.01) and no application of chemotherapy (p = 0.02) were statistically significant factors for OS. Conclusion Tumor histology, age at time of diagnosis and progesterone receptor status were prognostic factors for US. Unfavorable OS in LMS patients was associated with advanced FIGO stage, suboptimal cytoreduction and application of chemotherapy.

Clinical implications of morular metaplasia in fertility-preserving treatment for atypical endometrial hyperplasia and early endometrial carcinoma patients

Abstract Objective Morular metaplasia (MM) is a benign epithelial metaplasia that sometimes appears in atypical endometrial hyperplasia (AEH) and endometrioid endometrial carcinoma (EEC). However, the clinical implications of MM for fertility-preserving treatment in AEH and EEC patients are unclear. This study investigated the clinical features and impact of MM on the efficacy of fertility-preserving treatment. Methods We retrospectively studied 427 AEH and EEC patients who received fertility-preserving treatment. Clinical features, treatment efficacy, and onco-fertility results were compared between patients with and without MM. Results MM appeared in 147 of 427 (34.4%) patients. Among them, 49 (33.3%) had MM only before treatment (BEF group), 32 (21.8%) had sustained MM before and during treatment (SUS group), and 66 (44.9%) had MM only during treatment (DUR group). The BEF group had a higher 12-month CR rate (98.0% vs 85.7%, p = 0.017) and shorter therapeutic duration to achieve CR (4.0 vs 5.7 months, p = 0.013) than the non-MM group had. In comparison with the non-MM group, the SUS and DUR groups had a lower CR rate after 7 months of treatment (SUS vs non-MM, 37.5% vs 61.1%, p = 0.010; DUR vs non-MM 33.3% vs. 61.1%, p &lt; 0.001), and a longer median therapeutic duration to achieve CR (SUS vs non-MM, 7.6 vs. 4.0 months, p = 0.037; DUR vs non-MM, 7.9 vs. 4.0 months, p &lt; 0.001). Conclusion Appearance of MM only before treatment was positively correlated with outcome of fertility-preserving treatment, while sustained MM or appearance of MM only during treatment implied poorer outcome of fertility-preserving treatment in AEH and EEC patients.

Prognostic significance of CTNNB1 mutation in early stage endometrial carcinoma: a systematic review and meta-analysis

Abstract Background In the last years, mutations in the exon 3 of CTNNB1 have emerged as a possible prognostic factor for recurrence in early stage endometrioid endometrial carcinoma, especially in cases with no specific molecular profile (NSMP). Objective To define the prognostic value of CTNNB1 mutations in early stage endometrioid endometrial carcinoma, through a systematic review and meta-analysis. Methods Electronic databases were searched from their inception to November 2020 for all studies assessing the prognostic value of CTNNB1 mutation in early stage (FIGO I–II) endometrioid endometrial carcinoma. Odds ratio (OR) for tumor recurrence and hazard ratio (HR) for disease-free survival (DFS) were calculated with a significant p value &lt; 0.05. Results Seven studies with 1031 patients were included. Four studies were suitable for meta-analysis of OR and showed significant association between CTNNB1 mutation and the absolute number of recurrence (OR = 3.000; p = 0.019); the association became stronger after excluding patients with known molecular status other than NSMP (HR = 5.953; p = 0.012). Three studies were suitable for meta-analysis of HR and showed no significant association between CTNNB1 mutation and decreased DFS (HR = 1.847; p = 0.303); the association became significant after excluding patients with known molecular status other than NSMP (HR = 2.831; p = 0.026). Conclusion CTNNB1 mutation is significantly associated with recurrence in early stage endometrioid endometrial carcinomas, especially in the NSMP, appearing potentially useful in directing adjuvant treatment.

Impact of lymphadenectomy on short- and long-term complications in patients with endometrial cancer

Abstract Introduction Early endometrial cancer is primarily treated surgically via hysterectomy, adenectomy and, depending on tumor stage and subtype, lymphadenectomy. Systematic lymph node dissection is known to cause surgical complications. The aim of the present study was to investigate morbidity and mortality rates associated with lymphadenectomy in patients with endometrial cancer who underwent surgery in a routine clinical setting. Methods We collected data from 232 patients who were operated for endometrial carcinoma between 2006 and 2018 at the University of Lubeck, Germany. Surgical complications were viewed in relation to surgical risk factors. Additionally, a questionnaire concerning long-term lymphatic complications and survival was completed. Survival was compared between patients who underwent lymphadenectomy (group I) and those who did not (group II). Results Patients in group I needed revision surgery significantly more often due to postoperative complications (such as lymphoceles) compared to those in group II ( p  = 0.01). The results indicate more serious complications in patients who underwent a systematic lymphadenectomy and in those with lymph node metastases. 15% of patients who underwent a systematic lymphadenectomy had lymph node metastases. Recurrences occurred in 12.5% of cases and were significantly more frequent in patients who had undergone a lymphadenectomy, even if the lymph nodes were negative ( p  = 0.02). A comparison of survival data during the follow-up period revealed no significant difference. The study highlighted the need for a better preoperative risk stratification and the avoidance of lymphadenectomy for surgical staging alone.

A questionnaire-based survey on the diagnostic and therapeutic approaches for patients with STIC in Germany

Abstract Purpose Despite the growing understanding of the carcinogenesis of pelvic high-grade serous carcinoma (HGSC) of the ovary and peritoneum and its precursor lesion serous tubal intraepithelial carcinoma (STIC), evidence-based proven recommendations on the clinical management of patients with STIC are lacking so far. Methods A questionnaire containing 21 questions was developed to explore the clinical experience with patients with the diagnosis of STICs and the diagnostic, surgical and histopathological approaches in Germany. Overall, 540 clinical heads of department in all German gynaecological centres were asked to participate. Results 131 questionnaires (response rate 24.3%) were included in this survey. 45.8% of the respondents had treated one to three STIC patients during their career. 75.6% of the respondents performed opportunistic bilateral salpingectomies during other gynaecological surgeries. Most of the participants (31.3%) started with the SEE-FIM (Sectioning and Extensively Examining the FIMbria) protocol in 2014. It was requested by 39.7% centres for prophylactic salpingectomies, by 13.7% for both prophylactic and opportunistic salpingectomies and by 22.1% for neither of both. 38.2%, 1.5% and 24.4% of the participants would use the laparoscopic, transverse and midline laparotomic approach for a surgical staging procedure, respectively. 25.6% (54.7%) of the respondents recommended a hysterectomy in premenopausal (versus postmenopausal) patients with a STIC, 24.4% (88.4%) a bilateral oophorectomy and 50.0% (4.7%) an affected side oophorectomy (all p values &lt; 0.001). Omentectomy, pelvic and para-aortic lymphadenectomy would be performed by 60.5% (64.0%), 9.3% (11.6%) and 9.3% (11.6%) of respondents in premenopausal (versus postmenopausal) patients (all p values &gt; 0.05). Conclusion Our survey highlights significant inconsistency in the management of patients with STIC. Prospective data are urgently needed to elucidate the clinical impact of a STIC lesion and its clinical management.

Patient-initiated follow-up of early endometrial cancer: a potential to improve post-treatment cardiovascular risk?

Abstract Purpose Is patient-initiated follow-up, post-surgical treatment of early endometrial cancer safe and can it be used holistically to improve cardiovascular health? What are the cost implications of this model of follow-up? Methods Retrospective data of 98 patients discharged to patient-initiated scheme since 2012. Service evaluation by anonymous patient feedback including physical health effects of the programme including weight loss. Financial cost was compared to traditional hospital-based follow-up over five years. Results No evidence of recurrence over 54 months median follow-up in low-risk endometrioid endometrial cancer. Patient feedback indicates that the exercise course helped women reduce their BMI. Over one third women felt happier and one fifth felt more confident and had a better ability to cope with stress. Total of 91% patients would recommend this model of follow-up to friends or family in the same circumstance. European Society for Medical Oncology guidance suggests the number of hospital-based follow-up appointments required for this cohort would cost £109,760. Calculations in this paper examine the cost of patient-initiated follow-up and reflect an overall saving of around 96.5%. Conclusion This service evaluation supports the claim that patient-initiated follow-up represents a safe alternative to the traditional hospital-based protocol. There is a potential for additional services to be offered to encourage and promote a healthy lifestyle linked to improving quality of life and cardiovascular survival following surgery for endometrial cancer. Implications for cancer survivors Cardiovascular morbidity is the most common cause of death in endometrial cancer survivors. Incorporating an exercise course as part of routine follow-up can help reduce this risk. The friendships formed by this communal follow-up can contribute towards emotional health and recovery. This holistic approach should be incorporated into novel follow-up strategies to help reduce patient BMI and reduce cardiovascular risk.

Clinical features of ProMisE groups identify different phenotypes of patients with endometrial cancer

Abstract Background The Proactive Molecular Risk Classifier for Endometrial Cancer (ProMisE) groups has identified four molecular prognostic groups of endometrial cancer (EC): POLE-mutated (POLE-mt), mismatch repair-deficient (MMR-d), p53-abnormal (p53-abn), p53-wild-type (p53-wt). These groups might have different pathogenesis and risk factors, and might occur in different phenotypes of patients. However, these data are still lacking. Objective To provide a clinical characterization of the ProMisE groups of EC. Methods A systematic review and meta-analysis was performed by searching seven electronic databases from their inception to December 2020, for all studies reporting clinical characteristics of EC patients in each ProMisE group. Pooled means of age and BMI and pooled prevalence of FIGO stage I and adjuvant treatment in each ProMisE group were calculated. Results Six studies with 1, 879 women were included in the systematic review. Pooled means (with standard error) and prevalence values were: in the MMR-d group, age = 66.5 ± 0.6; BMI = 30.6 ± 1.2; stage I = 72.6%; adjuvant treatment = 47.3%; in the POLE-mt group, age = 58.6 ± 2.7; BMI = 27.2 ± 0.9; stage I = 93.7%; adjuvant treatment = 53.6%; in the p53-wt group, age = 64.2 ± 1.9; BMI = 32.3 ± 1.4; stage I = 80.5%; adjuvant treatment = 45.3%; in the p53-abn group, age = 71.1 ± 0.5; BMI = 29.1 ± 0.5; stage I = 50.8%; adjuvant treatment = 64.4%. Conclusion The ProMisE groups identify different phenotypes of patients. The POLE-mt group included the youngest women, with the lower BMI and the highest prevalence of stage I. The p53-wt group included patients with the highest BMI. The p53-abn group included the oldest women, with the highest prevalence of adjuvant treatment and the lowest prevalence of stage I. The MMR-d group showed intermediate values among the ProMisE groups for all clinical features.

Sentinel lymph node biopsy versus pelvic lymphadenectomy for early-stage cervical cancer: a retrospective institutional review

Abstract Objective To evaluate the oncologic and survival outcomes in patients diagnosed with early-stage cervical cancer who underwent both sentinel lymph node (SLN) and pelvic lymphadenectomy (PLD) compared with those who underwent SLN alone at primary surgery. Methods From 2001 to 2022, women who underwent SLN biopsy for nodal staging were recruited. The group of women who underwent SLN biopsy and PLD (SLN + PLD group) was compared with the group who underwent SLN mapping alone (SLN group). Results 210 patients were evaluated (98 and 112 in each group). The overall SLN detection rate was 97.6%. Lymph node involvement was detected in 23 patients (11%), and the rate of positive SLN increased from 6.2 to 11% after final pathological examination. At a median follow-up of 80 months, the recurrence and mortality rates were 6.2 and 2.4%, respectively. The 3-year progression-free survival (PFS) rate was 93.7 and 97.2%, and the overall survival (OS) rate was 98.9 and 99.0% in the SLN + PLD and SLN group, respectively. There were no significant differences in the Kaplan–Meier PFS (p = 0.471; HR 0.66; 95% CI 0.22–2.04) and OS (p = 0.228; HR 0.28; 95% CI 0.03–2.53) curves between the groups. Conclusion Pending further confirmation from prospective trials, SLN biopsy appears to be an effective method of nodal assessment in early-stage cervical cancer. This technique does not appear to increase the risk of recurrence compared with complete PLD in selected patients and may offer a viable, less invasive alternative for accurate nodal staging.

Comparison of surgical and postoperative pregnancy outcomes between electrotomy and cold instruments for hysteroscopic myomectomy: a single-center, 3-year retrospective study

Abstract Purpose To compare and analyze surgical outcomes and postoperative pregnancy outcomes between electrotomy and cold instruments for hysteroscopic myomectomy. Methods This study included patients who were diagnosed with submucosal fibroids (FIGO 0-2) in our center and underwent hysteroscopic myomectomy from January 2022 to November 2024. Hysteroscopic myomectomy was performed by either bipolar system or cold instruments. Surgical and postoperative pregnancy outcomes were recorded and analyzed. Results A total of 36 patients underwent hysteroscopic myomectomy at our center during the 3-year period, 21 in the cold instruments group and 15 in the electrotomy group. The mean age of the patients in the cold instruments group was significantly higher than that of the electrotomy group (39.00 ± 5.18 vs 35.20 ± 3.45, P = 0.019). In the electrotomy group, four patients found residual fibroids and required a second surgery. The incidence of residual fibroids and a second procedure were significantly higher than those in the cold instruments group (4/15(26.67%) vs 0, P = 0.023). The postoperative biochemical pregnancy rate and clinical pregnancy rate were higher in patients in the cold instruments group, but the difference was not statistically significant (14/21 (66.67%) vs 8/15 (53.33%), P = 0.644; 10/21(47.62%) vs 5/15(33.33%), P = 0.607). Conclusion Cold instruments for hysteroscopic myomectomy seem to be a safe and feasible surgical procedure. It has an advantage over electrotomy in terms of complete removal of submucosal fibroids. Moreover, cold instruments for hysteroscopic myomectomy have no electrothermal damage to normal endometrium, which is favorable for pregnancy as soon as possible after surgery.

Safety and effectiveness of transcervical radiofrequency ablation for uterine fibroids in patients with obesity: a retrospective cohort study

Abstract Key message Transcervical radiofrequency ablation is a low-risk, uterus-preserving option for symptomatic fibroids in women with obesity with significant improvement of bleeding disorder, including ≥ 40 kg/m 2 . Obesity should not preclude offering TFA. Objective To evaluate the safety and effectiveness of transcervical radiofrequency ablation (TFA) for uterine fibroids in women with obesity. Methods Retrospective multicenter cohort at two German Fibroid Centers. From 574 consecutive TFA cases, we included patients with BMI ≥ 30 kg/m 2 and ≥ 6-month follow-up; those with incomplete data were excluded. Fibroids were characterized by ultrasound. TFA (Sonata®) was performed per instructions for use. Outcomes were perioperative complications and patient-reported improvement in abnormal uterine bleeding (AUB). Results Sixty patients were analyzed (age 43.59 ± 6.52 years; BMI 35.72 ± 6.72 kg/m 2 ). Mean operative and ablation times were 33.65 and 9.91 min, respectively. One intraoperative bleeding event (1.7%) was controlled with a balloon catheter; no postoperative complications occurred. Mean follow-up was 17.08 months (6–54). Overall, 42/60 (70.0%) reported AUB improvement. By BMI category: 30–34.9 kg/m 2 25/39 (64.1%), 35–39.9 kg/m 2 5/7 (71.4%), ≥ 40 kg/m 2 12/14 (85.7%) (p = 0.3168). Considering the initial assessment, 48/60 (80.0%) improved; six later recurred, yielding 42/60 (70.0%) at last follow-up. Conclusion TFA showed a very low complication rate and clinically meaningful bleeding improvement in women with obesity, with comparable outcomes across BMI strata, including ≥ 40 kg/m 2 . Obesity is not a barrier to safe, effective TFA. Prospective, BMI-stratified studies with validated bleeding measures and objective endpoints are warranted.

Impact of diagnostic laparoscopy on resectability and treatment strategy in FIGO III–IV ovarian cancer

Abstract Objective To investigate the clinical utility of diagnostic laparoscopy in guiding treatment strategy and surgical outcomes for patients with advanced-stage ovarian cancer, specifically regarding operability assessment and the likelihood of complete cytoreduction. Methods This retrospective cohort study analyzed 183 patients with histologically confirmed International Federation of Gynecology and Obstetrics (FIGO) stage III–IV ovarian cancer treated with curative intent between January 2018 and December 2023 at a tertiary referral center. Patients were divided into two groups: those who underwent diagnostic laparoscopy prior to primary treatment ( n  = 80) and those managed without laparoscopy ( n  = 103). Laparoscopy was selectively employed when operability was uncertain. The primary outcome was the rate of complete macroscopic tumor resection. Secondary endpoints included intraoperative inoperability, neoadjuvant chemotherapy (NACT) rates, and surgical complexity. Statistical analyses included chi-square tests and predictive value calculations. Results Complete macroscopic resection was achieved in 57.5% of patients in the laparoscopy group compared to 68.0% in the control group. Among FIGO III cases, complete resection was lower in the laparoscopy group (63.0% vs. 77.0%), while rates were similar for FIGO IV (53.8% vs. 54.8%). Diagnostic laparoscopy had a positive predictive value of 59% and was a statistically significant, albeit weak, predictor of operability ( p  = 0.003, phi = 0.13). Patients in the laparoscopy group were more frequently triaged to NACT (78.8% vs. 50.5%). Intraoperative inoperability was also higher (29% vs. 14%). Conclusion Diagnostic laparoscopy influenced treatment strategy by increasing NACT use and reducing non-beneficial surgeries. Though it did not improve overall cytoreduction rates, it enabled personalized treatment planning, especially in patients with ambiguous resectability, thereby potentially lowering surgical morbidity.

Combined transcervical radiofrequency ablation and hysteroscopic myomectomy: expanding treatment to diverse fibroid types

Abstract Introduction Uterine fibroids are highly prevalent and often symptomatic, leading to abnormal uterine bleeding (AUB) and impaired quality of life. While hysteroscopic myomectomy (HSC) is the gold-standard treatment for submucosal fibroids, it is limited in addressing deeper lesions. Transcervical radiofrequency ablation (TFA) offers a minimally invasive alternative for intramural and transmural fibroids. This study evaluated the safety and effectiveness of combining TFA with HSC in a single session compared to HSC alone. Study design We conducted a retrospective multicenter analysis of 127 women with symptomatic fibroids and AUB. Patients underwent either combined TFA + HSC (n = 75) or HSC alone (n = 52). Outcomes included intraoperative bleeding, complications, and symptom improvement. Results The combined group treated a broader range of fibroid types (FIGO 0–6) and larger fibroids (mean size 2.86 cm vs. 2.23 cm; p = 0.0013). Intraoperative bleeding was significantly lower in the combined group (0% vs. 9.6%; p = 0.0102), with no increase in total complication rates (8% vs. 15%; p = 0.2512). Among patients with follow-up data, 85.1% reported symptom improvement after combined treatment. Conclusion Combining TFA with hysteroscopic myomectomy is a safe and effective approach that expands the range of treatable fibroids, reduces intraoperative bleeding, and maintains high patient satisfaction. This integrated strategy offers advantages in tissue diagnosis, potential cost savings, and uterine preservation, making it a valuable addition to minimally invasive fibroid management.

Preoperative colonoscopy in ovarian cancer: impact on surgical planning and outcomes: results from a retrospective, single-center study

Abstract Background Diagnosis and management of ovarian cancer remain complex due to the overlap of symptoms with other malignancies and the variability in preoperative diagnostic approaches. While histological confirmation is crucial, the role of preoperative colonoscopy in improving surgical planning and patient outcomes remains unclear. Objective This study aims to evaluate the impact of preoperative colonoscopy on surgical outcomes, peri-operative complications and interdisciplinary coordination in ovarian cancer patients. Methods A retrospective, single-center study was conducted at the University Medical Center Freiburg, including 306 patients diagnosed with malignant ovarian tumors between 2016 and 2023. Patients were stratified into two groups: those who underwent preoperative colonoscopy (n=104) and those who did not (n=202). Tumor characteristics, diagnostic findings, and surgical outcomes were compared. Primary endpoints included the detection of abnormal colonoscopic findings and their correlation with intraoperative interventions. Secondary endpoints assessed the impact of colonoscopy on macroscopic complete resection rates and peri-operative complications. Results Patients undergoing preoperative colonoscopy exhibited higher rates of advanced tumor stages (FIGO III/IV: 84.5% vs. 47.5%). Abnormal colonoscopic findings were observed in 38.8% of cases, yet colorectal resections were performed in only 53% of these patients. Despite a higher frequency of neoadjuvant chemotherapy in the colonoscopy group (57.3 vs. 33.7%), macroscopic complete resection rates were lower (67.0 vs. 79.2%). Sensitivity and specificity analyses indicated moderate predictive accuracy of colonoscopy for colorectal involvement (67 and 74%, respectively). In advanced ovarian cancer, preoperative colonoscopy influenced colorectal surgery decisions, with higher resection rates but minimal impact on neoadjuvant chemotherapy rates, despite moderate sensitivity and specificity. Conclusion While preoperative colonoscopy identified colorectal involvement in a subset of ovarian cancer patients, particularly in advanced tumor stages, its impact on surgical decision-making, oncological outcomes, and physicians' choice for neoadjuvant chemotherapy was limited. The findings suggest that intraoperative assessments remain the primary determinant for colorectal interventions. Future prospective studies are warranted to clarify the clinical utility of colonoscopy in preoperative evaluation and its potential influence on interdisciplinary surgical strategies. Retrospectively registered study 24-1364-S1-retro

Timing and survival benefits of cytoreduction in patients with recurrent leiomyosarcoma

Leiomyosarcoma is characterized by its aggressive behavior, poor prognosis, resistance to chemotherapeutic drugs, and high recurrence rate. This study aimed to identify prognostic factors affecting the effectiveness of cytoreductive surgery (CRS) on overall survival (OS) in patients with recurrent leiomyosarcoma (LMS). A retrospective analysis was conducted at Başkent University Ankara Hospital from 2007 to 2016, involving 59 patients with uterine LMS who underwent surgery. We assessed demographic and clinical variables, disease recurrence intervals, and treatment outcomes. The median age of the patients was 50.0 (23-78) years, and the median follow-up time was 25.0 (2-87) months. Median disease-free survival (DFS) and OS were 15.0 and 37.0 months, respectively. Disease recurrence occurred in 44 patients (74.6%). After recurrence, 34 (77.3%) patients underwent CRS and chemotherapy (CT), while 10 (22.7%) patients received only CT. The median OS was 19.0 months for patients who underwent CRS and received CT and 15.0 months for those who received only CT (p = 0.132). Notably, OS was significantly longer for patients whose recurrence occurred after 6 months compared to those with early recurrence (19 versus 8 months, p = 0.049). CRS provided a modest survival benefit for patients with recurrent LMS, although statistical significance was not achieved. The results of this study indicate that the timing of recurrence plays a crucial role in survival.

Mini-laparotomic-assisted laparoscopic radical hysterectomy: an innovative technique for cervical cancer surgery—a case series

Abstract Purpose To assess the feasibility, safety, and short-term surgical outcomes of mini-laparotomic-assisted laparoscopic radical hysterectomy in the treatment of early-stage cervical cancer. This pilot feasibility case series is the first to provide a detailed description of the technique and its initial clinical results. Methods A retrospective case series of seven women with early-stage cervical cancer underwent mini-laparotomic-assisted laparoscopic radical hysterectomy at a single tertiary care center between November 2023 and October 2024. The surgical procedure included laparoscopic pelvic lymphadenectomy, radical hysterectomy, and salpingectomy, followed by colpotomy and uterine extraction through a mini-laparotomy (4–8 cm). Data on baseline characteristics, intraoperative parameters, and postoperative outcomes were collected and analyzed retrospectively. Results The median age was 50 years (range 42–76), and the median BMI was 27.9 kg/m 2 (range 20–43). Histological subtypes included five cases of squamous cell carcinoma, one case of adenocarcinoma, and one case of adenosquamous carcinoma. Pathological staging revealed IB2 in three patients, IA1 in two, and one each for IB1 and IA2. The median operative time was 345 min (range 295–395), and the median estimated blood loss was 500 mL (range 200–700). No intraoperative or postoperative complications were reported. Conclusion Mini-laparotomic-assisted laparoscopic radical hysterectomy appears to be a feasible and safe surgical option for early-stage cervical cancer. This technique combines the oncologic rigor of open surgery with the advantages of minimally invasive methods, addressing significant limitations of conventional laparoscopy, including tumor manipulation and intracorporeal colpotomy performed under CO₂ pneumoperitoneum. As the initial report describing this approach, the findings support its potential as an effective alternative to the traditional open radical hysterectomy. Further studies involving larger cohorts and long-term follow-up are needed to validate its oncologic and perioperative benefits.

The role of computed tomography in the assessment of tumour extent and the risk of residual disease after upfront surgery in advanced ovarian cancer (AOC)

Abstract Purpose Epithelial ovarian cancer is usually diagnosed in the advanced stages. To choose the best therapeutic approach, an accurate preoperative assessment of the tumour extent is crucial. This study aimed to determine whether the peritoneal cancer index (PCI), the amount of ascites, and the presence of cardiophrenic nodes (CPLNs) visualized by computed tomography (CT) can assess the tumour extent (S-PCI) and residual disease (RD) for advanced ovarian cancer (AOC) patients treated with upfront surgery. Methods In total, 118 AOC cases were included between January 2016 and December 2018 at Skåne University Hospital, Lund, Sweden. Linear regression and interclass correlation (ICC) analyses were used to determine the relationship between CT-PCI and S-PCI. The patients were stratified in complete cytoreductive surgery (CCS) with no RD or to non-CCS with RD of any size. The amount of ascites on CT (CT-ascites), CA-125 and the presence of radiological enlarged CPLNs (CT-CPLN) were analysed to evaluate their impact on estimating RD. Results CT-PCI correlated well with S-PCI (0.397; 95% CI 0.252–0.541; p &lt; 0.001). The risk of RD was also related to CT-PCI (OR 1.069 (1.009–1.131), p &lt; 0.023) with a cut-off of 21 for CT-PCI (0.715, p = 0.000). The sensitivity, specificity, positive predictive value and negative predictive value were 58.5, 70.3, 52.2 and 75.4%, respectively. CT-ascites above 1000 ml predicted RD (OR 3.510 (1.298–9.491) p &lt; 0.013). Conclusion CT is a reliable tool to assess the extent of the disease in advanced ovarian cancer. Higher CT-PCI scores and large volumes of ascites estimated on CT predicted RD of any size.

Removal of FIGO V and VI fibroids with a combined size greater than 5 cm quadruples spontaneous fecundity relative to myomectomy for those with smaller fibroids

Abstract Purpose Fibroids are the most common gynecological pathology in reproductive aged women and contribute to 2–3% of infertility cases. After hysteroscopic removal of submucosal FIGO 0 and I fibroids, pregnancy rates of 60% to 90% can be achieved. Pregnancy rates after non-hysteroscopic removal of subserosal FIGO V and VI fibroids remain controversial. Methods We examined all myomectomies per laparoscopy/laparotomy for FIGO V and VI fibroids performed at the Clinical Division of Gynecological Endocrinology and Reproductive Medicine, Medical University of Vienna, from 2012 to 2021. All women with primary and secondary infertility between the ages of 18 and 40 years with 1–3 subserous fibroids without additionally identified causes for infertility were included. The outcome was the clinical pregnancy rate within 12 months after a postoperative non-conception window. A logistic regression model was used to assess associations between patient characteristics and postoperative pregnancy rates. The association was estimated as odds ratio (OR) with the respective 95% confidence interval (CI). Results We included a total of 80 women with a median age of 34.5 years (IQR, 31.4–37.8). Of those, 42 patients (52.5%) had primary infertility and 38 patients (47.5%) had secondary infertility. Fibroid size ranged from 2 to 30 cm with a median size of 7.5 cm. Pregnancy occurred in 36 patients (45.0%) at a median of 4 months (IQR 3.0–7.0) after initial postoperative 6 months, where pregnancy was permitted. Age (OR 0.77, 95% CI 0.67–0.88) and fibroid size (OR 1.25; 95% CI 1.072–1.446) were significantly associated with the occurrence of a clinical pregnancy. Conclusion In this cohort of infertile women of reproductive age with FIGO V and VI fibroids, almost half became spontaneously pregnant within 12 months after a postoperative non-conception window of myomectomy per laparoscopy/laparotomy. Patients with larger fibroids were more likely to conceive after myomectomy.

Clinical routine care for choriocarcinoma: a descriptive analysis of data from the Baden-Wuerttemberg Cancer Registry (BWCR)

Choriocarcinoma is a rare tumour. In Germany, due to its low incidence and lack of centralisation in care, only limited data are available on real-world clinical practice. This study aims to analyse tumour characteristics, treatment, and outcomes of patients with gestational choriocarcinoma using data from the Baden-Wuerttemberg Cancer Registry (BWCR), Germany. We included patients aged 18-50 years diagnosed with choriocarcinoma between 2015 and 2023, reported to the BWCR. The cases were identified using ICD-O-3 codes 9100/3, 9101/3 and ICD-10-GM code C58.9. Diagnostic and treatment information was derived from standardised registry entries and pathology reports. First-line treatment was defined as therapy initiated within 120 days of diagnosis. Data were analysed using descriptive statistics. 38 patients (mean age 33.4 years) were included; 39% presented with metastatic disease, predominantly isolated lung metastases (67%). Systemic therapy was reported in 28 cases: MTX (n = 10), EMA-CO (n = 12), and - due to timecourse or substance - other regimens (n = 6). The reported treatment duration ranged from 20 - 120 days (MTX) and 50 -154 days (EMA-CO). One MTX-treated patient (10%) required escalation to EMA-CO. Among EMA-CO cases, therapy was discontinued in three patients and one second-line treatment reported. The reported adverse events were in line with published data. This population-based analysis provides real-world insights into choriocarcinoma care in Baden-Wuerttemberg. While outcomes align with current guidelines, observed resistance to MTX and EMA-CO highlights the need for individualised treatment and closer monitoring. These findings underline the value of registry data in guiding therapy optimization-even in rare diseases like choriocarcinoma.

Prognostic and predictive value of supradiaphragmatic lymph node involvement detected by 18F-FDG PET/CT in advanced ovarian cancer: a systematic review and meta-analysis

Abstract Objective To evaluate the prognostic and predictive significance of supradiaphragmatic lymph node (SDLN) positivity detected by 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) in patients undergoing primary cytoreductive surgery for advanced epithelial ovarian cancer. Methods A systematic review and meta-analysis was conducted according to PRISMA 2020 guidelines and registered with PROSPERO. Studies reporting on overall survival (OS), progression-free survival (PFS), and complete cytoreduction (R0) in patients with and without 18F-FDG PET/CT-detected SDLN metastases were identified through comprehensive database searches conducted on December 18, 2024. Data from five retrospective, single-center studies comprising a total of 605 patients were included in the quantitative synthesis. Meta-analyses were performed using a random-effects model. Results SDLN positivity on 18F-FDG PET/CT was significantly associated with worse survival outcomes and lower resection rates. The pooled hazard ratio (HR) for OS was 1.60 (95% CI 1.19–2.25, p  = 0.002) and for PFS 1.53 (95% CI 1.19–1.96; p  = 0.0009), indicating poorer prognosis in SDLN-positive patients. The odds of achieving complete cytoreduction were significantly reduced in this group (OR = 0.32, 95% CI 0.15–0.68, p  = 0.003). While heterogeneity was low for progression-free and overall survival ( I 2  = 0%), moderate heterogeneity was observed in the analysis of complete cytoreduction ( I 2  = 54%). None of the included studies provided histologic confirmation of 18F-FDG PET/CT-positive SDLNs. Conclusions 18F-FDG PET/CT-detected SDLN positivity is associated with worse survival and lower resectability in advanced ovarian cancer. Due to lacking histologic confirmation and retrospective data, prospective validation is needed.

The efficacy of progestins in managing pain associated with endometriosis, fibroids and pre-menstrual syndrome: a systematic review

Abstract Purpose Alongside being contraceptives, progestins have been investigated as potential anti-inflammatory and analgesic therapies for use in painful gynaecological conditions. This review aims to synthesise evidence pertaining to the efficacy of progestins as analgesics for use in endometriosis, fibroids and pre-menstrual syndrome (PMS). Methods We conducted a systematic review of the extant literature investigating the analgesic efficacy of progestins compared to any comparator interventions for individuals with the three specified gynaecological conditions. The search was carried out across the PubMed and CENTRAL databases on 7 April 2024 for randomised control trials (RCTs) published in the peer-reviewed literature from 2000 onwards. Data pertaining to analgesic efficacy, assessed by changes in pain indices/scores before and after treatment, were synthesised narratively. Data pertaining to adverse effect frequency and changes in bone mineral density (BMD) were also synthesised narratively. Risk of bias was assessed using the Cochrane risk of bias 2 tool. Results The primary search identified 1220 potentially eligible RCTs of which 21 were ultimately included; 19 RCTs related to endometriosis, two related to fibroids and zero related to PMS. Quality assessment identified nine studies to be at a low risk of bias, nine studies with some concerns surrounding bias and three studies to be at a high risk of bias. The included studies represented a total of 2745 participants of whom 1317 were treated with a progestin and 1428 received a comparator intervention. In 18 of the 19 studies concerning endometriosis, progestins produced a statistically significant reduction in pain, further, in five instances progestins were more efficacious in reducing pain than comparator interventions. In both studies on fibroids, progestins produced significant reductions in pain, however, statistically significant differences compared to comparator interventions were not demonstrated. The most frequently cited adverse effect of progestins was spotting/irregular bleeding whilst those receiving comparator interventions most often reported hot flushes; cited in 12 and seven studies respectively. Five studies assessed the impact of progestins and comparators on BMD. Three studies found progestins significantly reduced BMD, however, in these instances reductions were significantly lower than those produced by comparator interventions and in two studies were not statistically significant after 12 months of follow-up. Conclusion Our review demonstrates the potential scope for the use of progestins as analgesics in the management of pain associated with endometriosis. Further research will need to be conducted to identify their efficacy in the management of pain associated with fibroids and PMS.

Efficacy of GnRH antagonists in the treatment of uterine fibroids: a meta-analysis

Uterine fibroids are the most common pelvic tumors in women, representing the primary indication of hysterectomy. Gonadotropin-releasing hormone (GnRH) antagonists represent a new therapeutic option for premenopausal women. The aim of this review is to evaluate the efficacy and safety of GnRH antagonists in the treatment of uterine fibroids (size reduction and symptom control). A review of studies from electronic databases (PubMed and Cochrane Central) published up to December 2023 was performed. Eleven randomized clinical trials with a total of 4164 patients were included in the review, which evaluated GnRH antagonists (Relugolix, Elagolix, Linzagolix and Cetrorelix) against placebo or GnRH agonists in premenopausal women with uterine fibroids and heavy menstrual bleeding. The results of the measures evaluated to determine the efficacy and safety of GnRH antagonists versus placebo are favorable for the variables of control of uterine bleeding (Relative risk (RR) = 5.09; 95% CI 3.19 to 8.14), percentage reduction of fibroid volume (Mean difference (MD) = -27.36; 95% CI -38.89 to -15.83) and lower reduction of bone density (MD -0.35; 95% CI -0.47 to -0.24). The results do not allow us to conclude whether there are differences between the alternatives compared in the control of vasomotor symptoms. GnRH antagonists represent an effective alternative for uterine fibroids treatment as they allow a superior reduction in menstrual bleeding and uterine fibroid volume compared to the placebo group.

Factors affecting gasless reduced-port laparoscopic myomectomy (GRP-LM) using a subcutaneous abdominal wall lifting method: a retrospective analysis of a large cohort of 966 cases in Japan

Abstract Objective To evaluate the usefulness of gasless reduced-port laparoscopic myomectomy (GRP-LM) using a subcutaneous abdominal wall lifting method. Methods In GRP-LM, after lifting the abdominal wall by a subcutaneous abdominal wall lifting method, a 1.5-cm incision is made in the lateral abdomen, Lap Protector® is placed. The operation is performed by two surgeons, one who inserts multiple forceps from the Lap Protector and performs the operation, and an assistant who operates the laparoscope and uterine manipulator. The surgical outcome of GRP-LM and the factors that affect it were investigated. Results GRP-LM was performed in 966 patients. Complications (0.5%) and blood transfusions (0.3%) were remarkably rare, and there were no cases of conversion to open surgery. With regard to the correlation between the number of fibroids extracted and each factor, the number of fibroids extracted correlated with fibroid weight and operation time, but not with blood loss. The average number of sutures per case was 21, and the average suture and ligation time per suture was 77 s. Comparing the cost of GRP-LM with that of the conventional insufflation LM, a saving of $875 was possible with GRP-LM. Conclusion GRP-LM is a suitable for multiple fibroids, and is cosmetic and economical, because it allows rapid and reliable suture and ligation, despite having only one port for the procedure.

Quality assurance using quality indicators for prevention and early detection of cervical cancer in certified gynaecological dysplasia units and consultancies

Abstract Purpose Cervical cancer is the fourth most common cancer in women worldwide. A successful screening concept for cervical cancer reduces the incidence and mortality of cervical cancer. Quality indicators (QIs) derived from the screening guidelines for cervical cancer and used by the certified dysplasia units and dysplasia consultancies are evaluated in this paper. The aim of this paper is to present the current data from the annual reports of these units and consultancies. Methods The results of the basic data and indicators for the audit year 2022 in the gynaecological dysplasia consultancies and units are presented. In 2022, 84 dysplasia consultancies and 42 units were audited. 40 units and 84 consultancies are included in the annual report. QI outcomes for patients treated in certified dysplasia units and dysplasia consultancies are analysed. Median, overall proportion, and standard deviation were calculated for each QI. Results The indicator year 2021 was analysed, which was audited in 2022 and evaluated in 2023. A total of nine QIs were analysed. Most target goals were met by the 84 certified dysplasia consultancies and by the 40 dysplasia units. The QIs evaluated are implemented to a very high degree. The targets for the three QIs were achieved by both the dysplasia consultancies and the units in at least 95% of the certified centres (QI 1: 100%, QI 2: 95%, QI 3: 100%; QI 1: 100%, QI 2: 97%, QI 3: 100%, respectively). The presentation of patients to the tumour board by the consultancies/units is working; the units are attending the tumour board more regularly than in previous years. Where the target was not met, the auditors issued deviations or reduced the duration of the certificate. The cases are discussed intensively in the sense of an individual case analysis and with the determination of measures on-site. Conclusions The targets for the various indicators were largely met by the dysplasia consultancies and units in the 2022 audit year. The certification of gynaecological dysplasia consultancies/units which have to cooperate with certified gynaecological cancer centres, has for the first time ensured the continuity of healthcare from prevention and early diagnosis to treatment of gynaecological cancers.

Assessment of psychological distress in patients with cervical dysplasia according to age, education, information acquisition and information level

Abstract Purpose This study aims to investigate the psychological distress experienced by patients with an initial diagnosis of abnormal Pap smears or dysplastic changes of the cervix uteri. It investigated whether patients’ age, education, information level and approach to information acquisition have an impact on their psychological distress. Methods A total of 364 female patients, aged 20–80 years, referred to the special dysplasia consultation hour at the Department of Obstetrics and Gynecology, Wuerzburg, completed a questionnaire containing validated items to assess information level, information acquisition, information needs and psychological distress, including a distress thermometer. Data from questionnaires and medical reports were used for analysis. Results The study found that 56.9% of patients experienced psychological distress before their first visit. Patients under 44 years of age, especially those with concerns about fertility and sexuality, and those with lower levels of education showed higher levels of distress ( p -value = 0.018 and p -value = 0.037). 40.9% of patients felt poorly informed and 53.7% of patients wanted more information before their visit. Correlational analysis showed that the method of obtaining information correlated with the desire for more information ( p -value &lt; 0.001). Those who received information via the Internet felt less informed, wanted more information and experienced more anxiety. Conclusion These findings highlight the need for improved patient education strategies and effective doctor-patient communication to address the knowledge gap and reduce patient distress. In addition, healthcare providers should ensure that patients have access to reliable online resources for accurate information.

Value of endometrial biopsy in patients with hysteroscopically atrophic endometrium in patients with postmenopausal bleeding

Abstract Purpose To determine the rate of precancer and cancer in women presenting with PMB who have a visually atrophic endometrium at hysteroscopy and assess the value of endometrial biopsy in this situation and the adequacy of the samples obtained. Methods Retrospective reviews of all patients with a visually atrophic endometrium at hysteroscopy who had presented with PMB and had an ET &gt; / = 4 mm or ET &lt; 4 mm with focal changes or irregular features between 2013 and 2024 at University Hospitals of Derby and Burton were included (n = 1096). Patients who had previously had cancer or precancer or had unclear hysteroscopy findings were excluded. The endometrial biopsy histology result was considered the main outcome measure. Results 188 patients did not have a biopsy performed (17.15%), 660 patients had benign pathology (60.22%), and 239 patients had an inadequate sample result (21.81%). Nine patients had precancerous changes (0.82%). The rate of cancer was 0.00% (n = 0). The NPV of a visually atrophic endometrial cavity at hysteroscopy in detecting precancer or cancer was 99.2%. Patients with an ET &lt; 4 mm pre-hysteroscopy and an atrophic endometrial cavity at hysteroscopy were 2.25 times more likely than those whose ET is &gt; 4 mm to have an inadequate sample (p &lt; 0.001, 95% CI 1.61–3.16). 10 patients who had an inadequate sample at initial biopsy had a repeat inadequate sample (n = 23, 43.48%). Conclusions The incidence of precancer/cancer in patients presenting with PMB with a visually atrophic endometrium at hysteroscopy is low. Many patients within this cohort have an inadequate sample at biopsy, and therefore, repeat sampling is of questionable value.

Predicting recurrence in adult granulosa cell tumors: the role of Ki67, p53, and TERT mutations

Adult granulosa cell tumors (aGCTs) are a rare type of ovarian malignancy. While most aGCTs have an indolent course, up to 25% experience recurrence. Identifying markers for disease recurrence is crucial for optimal management. Our study consisted of a total of 55 patients, comprising primary non-recurrent aGCTs (n = 30), aGCT recurrences without corresponding primary tumors (n = 19), and primary aGCTs which later recurred along with their matched recurrences (n = 6). Immunohistochemical analysis was conducted for CD73, Ki67, and p53, along with TERT mutation analysis on selected tissue samples. Immunohistochemical analysis revealed higher Ki67 proliferation index in recurrent aGCTs compared to non-recurrent cases. Mutational p53 staining was only present in recurrent cases. CD73 expression did not differ significantly between primary non-recurrent and recurrent aGCTs. A notably increased occurrence of TERT promoter mutations was identified in recurrent aGCTs (14/25, 56%) in contrast to primary non-recurrent instances (8/27, 29.6%) (p = 0.05). In primary non-recurrent aGCTs with identified TERT mutations, the C250T locus was impacted in 2 cases, while the C228T locus was affected in 6 cases. Recurrent aGCT cases predominantly exhibited TERT C228T mutation in 13 out of 14 patients. Among the six pairs of primary and recurrent aGCTs studied, four pairs displayed TERT mutations in both primary and recurrence samples. Moreover, cases with TERT mutations exhibited a higher Ki67 index. Identifying patients with high Ki67 and mutational p53 together with TERT mutations may help predict potential recurrence in aGCT cases.

Secondary cytoreductive surgery in platinum-sensitive relapsed ovarian cancer: a meta-analysis of randomized controlled trials

To evaluate the role of secondary cytoreduction in patients with platinum-sensitive recurrent ovarian cancer. The PubMed, Medline, Embase, Cochrane Library and Web of Science databases were searched. Randomized controlled trials (RCTs) that compare secondary cytoreduction plus chemotherapy with chemotherapy alone in patients with platinum-sensitive relapsed ovarian cancer were selected. Pooled hazard ratios (HR) with 95% confidence intervals (CIs) were calculated. There was no difference in overall survival (OS) between the surgery group and no surgery group (HR = 0.89; 95% CI 0.77, 1.04; p = 0.14), but secondary cytoreduction showed a significant improvement in progression-free survival (PFS) (HR = 0.67; 95% CI 0.54, 0.76; p < 0.00001). A subgroup analysis comparing the complete gross resection subpopulation with the no surgery group achieved a significant longer OS (HR = 0.70, 95% CI 0.58-0.85; p = 0.0003) and a greater PFS benefit (HR = 0.56, 95% CI 0.48-0.66; p < 0.00001). In addition, as compared with incomplete resection, the OS benefit of complete gross resection was more evident (HR = 0.51, 95% CI 0.37-0.69; p < 0.0001). In women with platinum-sensitive recurrent ovarian cancer, although secondary cytoreduction followed by chemotherapy resulted in longer PFS than chemotherapy alone, it did not lead to significant benefit in OS. However, when complete gross resection was achieved, it significantly prolonged OS and provided a greater PFS benefit.

Exploratory study on the enhancement of O-RADS application effectiveness for novice ultrasonographers via deep learning

The study aimed to create a deep convolutional neural network (DCNN) model based on ConvNeXt-Tiny to identify classic benign lesions (CBL) from other lesions (OL) within the Ovarian-Adnexal Reporting and Data System (O-RADS), enhancing the system's utility for novice ultrasonographers. Two sets of sonographic images of pathologically confirmed adnexal lesions were retrospectively collected [development dataset (DD) and independent test dataset (ITD)]. The ConvNeXt-Tiny model, optimized through transfer learning, was trained on the DD using the original images directly and after automatic lesion segmentation by a U-Net model. Models derived from both training paradigms were validated on the ITD for sensitivity, specificity, accuracy, and area under the curve (AUC). Two novice ultrasonographers were assessed in O-RADS with and without assistance from the model for Application Effectiveness. The ConvNeXt-Tiny model trained on original images scored AUCs of 0.978 for DD and 0.955 for ITD, while the U-Net segmented image model achieved 0.967 for DD and 0.923 for ITD; neither showed significant differences. When assessing the malignancy of lesions using O-RADS 4 and 5, the diagnostic performances of two novice ultrasonographers and senior ultrasonographer, as well as model-assisted classifications, showed no significant differences, except for one novice's low accuracy. This approach reduced classification time by 62 and 64 min. The kappa values with senior doctors' classifications rose from 0.776 and 0.761 to 0.914 and 0.903, respectively. The ConvNeXt-Tiny model demonstrated excellent and stable performance in distinguishing CBL from OL within O-RADS. The diagnostic performance of novice ultrasonographers using O-RADS is essentially equivalent to that of senior ultrasonographer, and the assistance of the model can enhance their classification efficiency and consistency with the results of senior ultrasonographer.

A comprehensive diagnostic approach to differentiate intrauterine arteriovenous malformation in cases of enhanced myometrial vascularity

The differentiation between conditions such as uterine arteriovenous malformation, pseudoaneurysm, gestational trophoblastic disease, and retained trophoblastic tissue can be challenging. Ultrasound imaging and Doppler interrogation are the primary diagnostic tools to assess cases of enhanced myometrial vascularity and differentiate intrauterine vascular anomalies. However, some cases remain of difficult differentiation. This study aims to analyze suspected cases and describe their diagnostic management and outcomes. We reviewed post-abortion cases that underwent pelvic transvaginal U/S imaging and Doppler examinations due to suspected uterine vascular anomalies. CT scans were performed in cases in which ultrasound did not reach a diagnosis. Simple follow-up, medical or surgical therapy, or embolization of uterine arteries were performed according to the final diagnosis. From 2015 to 2022, we retrieved from electronic ultrasound records 22 cases of suspected vascular malformations. In eight cases, first-line U/S at admission excluded the suspected anomaly. In Five of the remaining 14 patients, uterine vascular anomalies were excluded upon a second-level  U/S based on angio-Doppler imaging and Doppler peak velocity interrogation. Nine cases underwent CT scan, and a digital angiography and embolization were performed in eight of these cases, of whom only two had a documented uterine arteriovenous malformation. Our triage proved that only two out of 22 suspected cases had a uterine arteriovenous malformation. This diagnosis is frequently misused in clinical practice. Our data confirm that enhanced myometrial vascularity should be used to encompass the spectrum of possible differential diagnosis. A precise step-by-step diagnostic method is of paramount importance to prevent unnecessary interventions.

Periostin’s role in uterine leiomyoma development: a mini-review on the potential periostin poses as a pharmacological intervention for uterine leiomyoma

Uterine leiomyomas, also known as fibroids or myomas, occur in an estimated 70-80% of reproductive aged women. Many experience debilitating symptoms including pelvic pain, abnormal uterine bleeding (AUB), dyspareunia, dysmenorrhea, and infertility. Current treatment options are limited in preserving fertility, with many opting for sterilizing hysterectomy as a form of treatment. Currently, surgical interventions include hysterectomy, myomectomy, and uterine artery embolization in addition to endometrial ablation to control AUB. Non-surgical hormonal interventions, including GnRH agonists, are connotated with negative side effects and are unacceptable for women desiring fertility. Periostin, a regulatory extra cellular matrix (ECM) protein, has been found to be expressed in various gynecological diseases including leiomyomas. We previously determined that periostin over-expression in immortalized myometrial cells led to the development of a leiomyoma-like cellular phenotype. Periostin is induced by TGF-β, signals through the PI3K/AKT pathway, induces collagen production, and mediates wound repair and fibrosis, all of which are implicated in leiomyoma pathology. Periostin has been linked to other gynecological diseases including ovarian cancer and endometriosis and is being investigated as pharmacological target for treating ovarian cancer, post-surgical scarring, and numerous other fibrotic conditions. In this review, we provide discussion linking pathological inflammation and wound repair, with a TGF-β-periostin-collagen signaling in the pathogenesis of leiomyomas, and ultimately the potential of periostin as a druggable target to treat leiomyomas.

The role of cervical elastography in the differential diagnosis of preinvasive and invasive lesions of the cervix

This study aims to evaluate the role of cervical elastography in the differential diagnosis of preinvasive and invasive lesions of the cervix. A total of 95 women participated in this prospective study and were divided into the following groups: 19 healthy subjects (group 1) with normal cervicovaginal smear (CVS) and negative human papillomavirus test (HPV DNA), 19 women with normal cervical biopsy and normal final pathological result of cervical biopsy (group 2), 19 women with low-grade squamous intraepithelial lesion (LSIL) (group 3), 19 women with high-grade squamous intraepithelial lesion (HSIL) (group 4), and 19 women with cervical cancer (group 5). Clinical, demographic, histopathological, and elastographic results were compared between these groups. Comparing groups, age (40.42 ± 8.31 vs. 39.53 ± 8.96 vs. 38.79 ± 9.53 vs. 40.74 ± 7.42 vs. 54.63 ± 12.93, p  0.05) (Table  2. As a result of the applied roc analysis, mean cervical elastographic stiffness degree (ESD) was found to be an influential factor in predicting cervical cancer (p < 0.05). The mean cut-off value was 44.65%, with a sensitivity of 94.7% and a specificity of 96.1% (Table 7). Measurement of ESD by elastography is a low-cost, easily applicable, and non-invasive indicator that can distinguish cervical cancer from normal cervical and preinvasive lesions. However, it is unsuitable for determining preinvasive cervical lesions from normal cervix.

The use of colposcopy for triage in HPV-positive women aged 65 years and older

Abstract Purpose Persistent high-risk HPV infection is associated with an elevated risk for prevalent CIN II + despite normal cytology (NILM). Our study aims to evaluate the clinical relevance of a persistent high-risk HPV infection without cytologic changes in women aged ≥ 65 and to determine the role of colposcopy for triage in these cases. Methods 211 patients aged ≥ 65 with persistent HPV infection and normal cytology (NILM) who presented for colposcopy at five certified centers between January 2021 and April 2022 were included in the study. Colposcopic findings, HPV subtypes, when available, histology and p16/Ki67 staining were assessed as well as individual risk factors such as smoking and previous HPV-related surgery. Results 87.7% (185/211) of the included women had a type 3 transformation zone. In 83.4% (176/211), a biopsy was taken [thereof 163 endocervical curettages (ECC)]. In 35/211 women (16.6%), sampling was not possible during colposcopy due to an inaccessible cervix, pain during examination or obliteration of the cervical canal. Out of these, 6 women received a diagnostic excision. CIN II + was detected in 10.6% of all histologies (excisional or biopsy) (20/182). 50% of the women with a CIN II + where HPV 16 positive. Taking only the women diagnosed with CIN III or AIS into account, (n = 12) 75% were HPV 16 positive. Interestingly, 80% of the women with CIN II + had an abnormal cytology when repeatedly taken during colposcopy, vice versa an endocervical lesion was diagnosed in 53% of women with abnormal repeat cytology (27/51). Conclusion The prevalence of CIN II + in women is ≥ 65 with persistent hr HPV infection but NILM cytology is similar to that in younger women. However, more than 85% of the women have a type 3 transformation zone. Colposcopy is, therefore, not helpful to diagnose the women who need treatment in this age group.

Application of transabdominal ultrasound- and laparoscopy-guided percutaneous microwave ablation for treating uterine fibroids: 24-month follow-up outcomes

To determine the ablation efficacy of transabdominal ultrasound- and laparoscopy-guided percutaneous microwave ablation (PMWA), to investigate whether the risk of damage to adjacent organs and endometrium due to this technique can be reduced or even avoided. We also evaluated the clinical efficacy of this technique in the treatment of uterine fibroids of different sizes and at different locations over a 24-month follow-up period. This study included 50 patients with uterine fibroids who underwent transabdominal ultrasound- and laparoscopy-guided PMWA from August 2018 to July 2020. Lesions were confirmed by pathology. The technical efficacy and complications of PMWA were assessed. The lesion diameter, lesion volume, lesion location, and contrast-enhanced ultrasound (CEUS) features before PMWA and within 24 h after PMWA were recorded. Magnetic resonance imaging (MRI) was used for follow-up at 3 and 6 months after PMWA. Transvaginal ultrasound was used for follow-up at 24 months after PMWA. A total of 50 patients with uterine fibroids received treatment. The median ablation rate of uterine fibroids was 97.21%. The mean lesion volume reduction rates were 32.63%, 57.26%, and 92.64% at 3, 6, and 24 months after treatment, respectively. The size and location of uterine fibroids did not significantly affect the ablation rate and the rate of lesion volume reduction. No major complication was found during and after the procedure. Transabdominal ultrasound- and laparoscopy-guided PMWA can be utilized to safely enhance the ablation rate while minimizing ablation time and avoiding harm to adjacent organs and the endometrium. This technique is applicable for treating uterine fibroids of different sizes and at varying locations. ChiCTR-IPR-17011910, and date of trial registration: 08/07/2017.

The impact of epigallocatechin gallate, vitamin D, and D-chiro-inositol on early surgical outcomes of laparoscopic myomectomy: a pilot study

A prospective investigation to assess the impact of 3 months of treatment with epigallocatechin gallate (EGCG), vitamin D and D-chiro-inositol (DCI) in the treatment of uterine fibroids (UF) with laparoscopic myomectomy as evidenced by surgical outcomes and effect on liver function. Non-pregnant or lactating women aged between 30 and 40 years were scheduled for laparoscopic myomectomy to treat symptoms or looking to conceive. After enrollment, patients were assigned to either (1) intervention group, assuming a total of 300 mg EGCG, 50 μg vitamin D, and 50 mg DCI divided in 2 pills per day for 3 months, or (2) control group, including untreated women scheduled to undergo laparoscopic myomectomy after 3 months. 91 patients completed the study. The comparison of the surgical outcomes between the intervention (n = 44) and the control (n = 47) groups revealed that the treatment significantly reduces the duration of surgery (41.93 ± 7.56 min vs 56.32 ± 10.63 min, p < 0.001). Moreover, the treatment also reduced blood loss during surgery (149.09 ± 25.40 mL vs 168.41 ± 21.34 mL, p < 0.001), resulting in treated patients having higher Hb levels at discharge 11.27 ± 0.82 mL vs 10.56 ± 0.82 mL, p < 0.01). The surgery induced an increase in AST and in total bilirubin regardless of the assigned group, and the treatment induced no change in liver function. Our data suggest that EGCG plus vitamin D, and DCI could represent a safe option for women with UF scheduled for laparoscopic myomectomy, improving surgical outcomes without affecting liver functionality.

Smooth muscle tumours of the uterus: MR imaging malignant predictive features—a 12-year analysis in a referral hospital in Portugal

To evaluate the magnetic resonance imaging (MRI) features that may help distinguish leiomyosarcomas from atypical leiomyomas (those presenting hyperintensity on T2-W images equal or superior to 50% compared to the myometrium). The authors conducted a retrospective single-centre study that included a total of 57 women diagnosed with smooth muscle tumour of the uterus, who were evaluated with pelvic MRI, between January 2009 and March 2020. All cases had a histologically proven diagnosis (31 Atypical Leiomyomas-ALM; 26 Leiomyosarcomas-LMS). The MRI features evaluated in this study included: age at presentation, dimension, contours, intra-tumoral haemorrhagic areas, T2-WI heterogeneity, T2-WI dark areas, flow voids, cyst areas, necrosis, restriction on diffusion-weighted imaging (DWI), apparent diffusion coefficient (ADC) values, signal intensity and heterogeneity after contrast administration in T1-WI, presence and location of unenhanced areas. The association between the MRI characteristics and the histological subtype was evaluated using Chi-Square and ANOVA tests. The MRI parameters that showed a statistically significance correlation with malignant histology and thus most strongly associated with LMS were found to be: irregular contours (p < 0.001), intra-tumoral haemorrhagic areas (p = 0.028), T2-WI dark areas (p = 0.016), high signal intensity after contrast administration (p = 0.005), necrosis (p = 0.001), central location for unenhanced areas (p = 0.026), and ADC value lower than 0.88 × 10 With our work, we demonstrate the presence of seven MRI features that are statistically significant in differentiating between LMS and ALM.

Hysteroscopic diode laser myolysis: from a case series to literature review of incisionless myolysis techniques for managing heavy menstrual bleeding in premenopausal women

Abstract Purpose This case series examined the safety and effectiveness of hysteroscopic myolysis using laser-induced interstitial thermo-therapy (LITT) for treating heavy menstrual bleeding (HMB) in premenopausal women with FIGO type 1 or 2 uterine fibroids, not planning for future fertility. Additionally, a comprehensive review of innovative, minimally invasive, incisionless myolysis techniques was conducted. Methods Women with HMB, sonographically diagnosed with a single FIGO type 1 or 2 fibroid, underwent hysteroscopic myolysis using the Leonardo® diode laser. Effectiveness was assessed via transvaginal ultrasound measurement of myoma size, volume and vascularization pre and post-procedure. Moreover, we also evaluated any improvements in symptoms using the Pictorial Blood Loss Assessment Chart (PBAC score) scores. Results The procedure resulted in significant HMB reductions and noticeable fibroid size, volume, and vascularization decrease in all three patients, with no reported complications. The literature review revealed both advantages and limitations of the minimally invasive, incisionless myolysis techniques. Conclusions Hysteroscopic laser myolysis is a safe and effective therapeutic intervention for patients experiencing HMB, diagnosed with FIGO type 1 or 2 fibroids, and not planning for future fertility. The procedure resulted in significant reductions in menstrual blood loss and fibroid size. Despite the promising results, it is essential to note the limitations of this report, including its case series design, a small number of patients, and a short follow-up period. Further research is necessary to confirm these results.

Loss of stromal CD73 expression plays a role in pathogenesis of polypoid endometriosis

To investigate whether CD73 had a role in the pathogenesis of polypoid endometriosis. Our study included 15 cases of polypoid endometriosis, which were diagnosed between 2005 and 2019. Clinical findings were gathered from archive files of relevant clinics and pathology reports. All glass slides were re-examined for confirmation of the diagnosis and the detection of additional microscopic findings. An immunohistochemical examination was performed using anti CD73 antibodies in 15 cases of polypoid endometriosis, and also in a control group that contained 9 cases of endometrial polyps and 9 cases of ovarian conventional endometriosis. In addition to standard gynecologic operations, major non-gynecologic procedures had to be performed in 7 cases. In two cases, the surgical team comprised only general surgeons, and a misdiagnosis of carcinoma was made during the frozen section in one case. The majority of the cases displayed gross polypoid lesions that measured 0.7-13 cm. The most common sites were the ovary and rectosigmoid colon. Microscopically, all lesions exhibited a fibrovascular stroma reminiscent of endometrial stroma, whereas glandular features varied. Immunohistochemical examinations revealed a significant loss of CD73 expression in the stroma of polypoid endometriosis in contrast to the control cases, which retained stromal CD73 expression (p < 0.0001). Both pathologists and surgeons performing abdominal surgeries should be aware of polypoid endometriosis because it mimics malignancy with its clinical, gross, and microscopic features. We also conclude that loss of stromal CD73 expression, due to its effect on the extracellular ATP/adenosine balance, may contribute to the pathogenesis of this rare form of endometriosis.

Survival impact of number of removed para-aortic lymph nodes in stage I epithelial ovarian cancer

The survival effect of presence or absence of lymphadenectomy in early-stage epithelial ovarian cancer (EOC) was priorly shown but the effect of number of removed lymph nodes kept in background. We aimed to evaluate the survival impact of number of removed lymph nodes and their localizations in stage I EOC. This study included 182 patients. The best cut-off levels for number of pelvic and para-aortic lymph nodes (PaLN) were 24 and 10, respectively. Univariate and multivariate survival analyses were performed for these cut-offs and other prognostic factors. The median age of the patients was 49. The median number of removed pelvic and paraartic lymph nodes were 29 and 9, respectively. The median overall (OS) and progression-free survival (PFS) were 67 and 50 months, respectively. The 5-year OS rate was 89.6%. Recurrence occured in 24 (19.5%) patients. In univariate analyses tumor grade (p: 0.005), pelvic LN number (p: 0.041) and PaLN number (p: 0.004) were the factors that were significantly associated with PFS. Tumor grade and PaLN number were independently and significantly associated with PFS in multivariate analyses (p: 0.015 and p: 0.017, respectively). In OS analyses, age, tumor grade, presence of LVI, number of pelvic and PaLNs were the significantly associated factors (p < 0.05 for all). In multivariate analyses, age and PaLN number were independently and significantly associated with OS (p: 0.011 and p: 0.021, respectively). The number and localizations of removed lymph nodes may have a survival affect in stage I EOC. We also think that this study may constitute a kernel point for larger prospective series on lymph node number and lymphatic regions.

What is behind the fear of cancer during menopausal hormone therapy in China?

The application of menopausal hormone therapy (MHT) is generally restricted most likely due to limited prescriptions by doctors. Fear of cancer risk may be a critical factor. We investigated the views of Chinese obstetricians and gynecologists on the relationship between hormone therapy and cancer risk. A self-administered web-based nationwide cross-sectional questionnaire. In total, 5243 medical workers responded to the questionnaire (response rate 94.5%); 4995 were certified obstetricians and gynecologists. Most were aged 36-55 years (70.9%), had > 10 years of working experience (68.5%), and worked at tertiary (34.8%) and secondary hospitals (49.1%); 70% of the clinicians were aware of the endometrial cancer risk caused by estrogen, and 20% considered progestogen to cause the same risk. Regarding breast cancer, while 67.9 and 74.8% of the clinicians viewed natural and synthetic estrogens as risk factors, respectively, only 41.7% identified the carcinogenic effect of progestins as higher than that of progesterone (26.7%). Approximately 75% of the participants believed synthetic estrogens and progestins constituted a risk for ovarian cancer (higher than the percentages for their natural counterparts); 13.0-21.1% of the respondents were worried about choriocarcinoma due to hormone treatment. Finally, 86.8% of obstetricians and gynecologists claimed to have poor knowledge regarding this field. Misconceptions and a lack of knowledge in this regard may result in the fear of cancer and could be the underlying causes of limited MHT prescriptions. We believe that scientific research, continued education, and the media all have roles to play in changing preconceived ideas regarding MHT prescriptions.

New biomarkers in peripheral blood of patients with ovarian cancer: high expression levels of miR-16-5p, miR-17-5p, and miR-638

Ovarian cancer is one of the most fatal gynecologic malignities. miR-16-5p, miR-17-5p, and miR-638 genes were found to have been associated with ovarian cancer in accordance with the data obtained from the previous microarray research performed by Tuncer et al. (J Ovarian Res 13(1):99, 2020). The expression levels of these miRNAs in the peripheral blood samples of 142 ovarian cancer patients, and 97 healthy controls were investigated for performing the validation, and to identify whether these genes were the possible biomarkers to be used in the early diagnosis of high-risk ovarian cancer patients, and in the prognosis of patients. The miRNA expression analysis was performed using the miRNA-specific cDNA synthesis, and real-time PCR methods following the RNA isolation from the peripheral blood lymphocytes. miR-16-5p, miR-17-5p, and miR-638 miRNA gene expression levels were found to have twofold higher expression levels in patient groups compared with the gene expression levels in healthy controls, and were statistically significant (p < 0.05). In addition, the comparison of the miRNA expression levels with the clinical data of patients showed that there was a significant difference with smoking history and the increased expression level of miR-17-5 (p: 0.007). There was a significant difference between the increased expression level of miR-638 with the locally advanced stage, and abdominal/pelvic metastatic patients (p: 0.03). The obtained data suggest that miR-16-5p, miR-17-5p, and miR-638 molecules might be the noninvasive biomarkers in identifying the ovarian cancer. However, the investigation and monitoring of the changeability of these biomarkers in benign ovarian diseases, and during the treatment must be performed in future studies for identifying the accurate diagnostic, and prognostic features of miRNAs.

Clinical indicators useful in decision-making about palliative chemotherapy for end-of-life ovarian cancer patients

Chemotherapy for end-of-life ovarian cancer patients is a complex and delicate problem. We evaluated whether active palliative chemotherapy is beneficial for such patients using inflammatory parameters, nutritional indicators, and the PPI (Palliative Prognostic Index), which predicts short-term prognosis. Thirty-six patients among 49 patients who died from ovarian cancer from 2014 to 2019 at our hospital were enrolled, whom clinical and laboratory data just before starting their final chemotherapy regimen could be obtained. Associations between the time from last chemotherapy to death and the following parameters were investigated: age, performance status, neutrophil/lymphocyte ratio (NLR), platelet/lymphocyte ratio, Modified Glasgow Prognostic Score (mGPS), Prognostic Nutritional Index (PNI) score, and PPI score. The median age was 57 (range 19-80) years. The median time from last chemotherapy to death was 45.5 (range 11-110) days. Eight patients (22%) died within 30 days of their last chemotherapy regimen. In univariate analysis, median survival time was significantly shorter in patients with higher NLR, mGPS 2, and higher PPI values; NLR (≥ median vs. < median): 32 (range 11-80) days vs. 54 (range 35-110) days, p = 0.008; mGPS (2 vs. 0-1): 42 (range 11-80) days vs. 96 (range 49-110) days, p = 0.012; and PPI score (≥ median vs. < median): 38 (range 11-74) days vs. 60 (range 18-110) days, p = 0.005. However, in multivariate analysis, no factors were identified as independent prognostic factors for survival. Parameters, such as NLR, mGPS, and PPI score, may be indicators for discontinuation of palliative chemotherapy, and may be useful for maximizing end-of-life care for ovarian cancer patients.

ERRα expression in ovarian cancer and promotes ovarian cancer cells migration in vitro

Ovarian cancer is the leading cause of death from a gynaecological malignancy in the developed world, and is characterized by invasion and metastasis and thus causes a high fatality rate. Estrogen-related receptor alpha (ERRα) has been demonstrated to play a widespread and pathophysiological relevant role in tumourigenesis and development. The aim of this study was to investigate the effect of ERRα expression on the progression of ovarian cancer. The correlation between ERRα expression level and clinical pathological parameters in ovarian cancer tissues were analysed via cancer public database CPTAC. The expression level of ERRα in ovarian cancer cells were confirmed by RT-qPCR and Western blot methods. The cellular ERRα expression was up-regulated by lentivirus transfection and down-regulated by specific antagonist. The invasion and metastasis capabilities of ovarian cancer cells were characterized by wound healing assay and trans-well chamber assay. The CPTAC database showed that the ERRα expression levels were higher in the late-stage and high-grade ovarian cancer tissues than in early-stage and low-grade tissues. Ovarian cancer cells with higher-expression ERRα exhibited stronger invasion and metastasis capabilities in vitro. After up-regulating the ERRα expression level, the invasion and metastasis capabilities of ovarian cancer cells were enhanced, while down-regulation weakened. Moreover, the wound sealing rate was positively correlated with the expression of ERRα mRNA expression level (r = 0.921, P < 0.01), and the cell invasiveness was also positively correlated with the cellular ERRα mRNA expression level (r = 0.926, P < 0.01). Our results suggest that ERRα may promote the progression of ovarian cancer, and may serve as a promising predictive biomarker.

Bioinformatic analysis of key pathways and genes shared between endometriosis and ovarian cancer

The purpose of the study is to identify potential key genes and pathways, using bioinformatics, underlying the potentially common molecular mechanisms between endometriosis (EMS) and ovarian cancer (OC). Two datasets were collected from the Gene Expression Omnibus database, and the limma package identified common differentially expressed genes (DEGs) in the EMS and OC groups compared to controls. Gene Ontology, Kyoto Encyclopedia of Genes and Genomes, gene interaction network, and module analyses identified the enriched pathways associated with DEGs. A protein-protein interaction (PPI) network was then constructed, and the CytoHubba plugin of Cytoscape was used to calculate the degree of connectivity for proteins in the PPI network. A total of 571 overlapping DEGs were identified between EMS and OC (vs. controls). Enriched DEGs were associated with 36 gene ontology terms and 7 Kyoto Encyclopedia of Genes and Genomes pathways, which were mainly associated with deactivation of the p53 signaling pathway. The Kaplan-Meier plotter platform confirmed the expression of the identified hub genes, and survival analysis suggested that CCNB1, CCNB2, BUB1B, CCNA2, KIF2C, and TOP2A are associated with decreased survival and disease-free survival rates of OC. The key pathways identified herein elucidate the possible mechanism by which EMS evolves into OC; further, the identified hub genes may serve as potential biomarkers to predict OC occurrence and prognosis.

The fetal outcomes after neoadjuvant platinum and paclitaxel chemotherapy during pregnancy: analysis of three cases and review of the literature

Data on the outcomes of fetus who are exposed to neoadjuvant platinum and paclitaxel chemotherapy during pregnancy are lacking. Relevant data were abstracted from patients in our institution, PubMed, Embase and Cochrane Library databases. The primary assessment was the frequency of fetal death and congenital abnormalities. The secondary assessment was other negative fetal/infant outcomes including FGR, RDS, secondary malignant diseases and other recorded adverse events. Of the three infants in our center who exposed to platinum and paclitaxel chemotherapy during pregnancy, the physical evaluation and qualified Denver Developmental Screening Test showed normal findings at the last follow-up (19-24 months). Hearing evaluation among three children also showed normal findings. Another 34 infants (including a twins) of 21 studies in previous studies who exposed to platinum and paclitaxel chemotherapy during pregnancy were included in the final analysis. Of the 37 infants identified, 24 were exposed to cisplatin plus paclitaxel, and 13 were exposed to carboplatin plus paclitaxel. None of the 37 fetuses was abortion or dead during the pregnancy. 97.3% (36/37) infants were delivered by cesareans and the median gestational ages of delivery were 34.76 weeks (95% CI, 34.08-35.44). 1 fetus showed intrauterine growth restriction and one was found with left-sided ventriculomegaly and hydramnios before chemotherapy. Adverse events occurred in 18.9% (7/37) infants at birth, including two RDS, one hearing loss, one pathological jaundice, one first-degree intraventricular hemorrhage, one erythema, one corresponding to -0.5 standard deviation from average body weight of the same gestational weeks. No reports of neonatal cardiologic abnormalities are reported in these infants after the initiating of chemotherapy. The infant with congenital anomaly died 5 days after birth. During the follow-up, 5.4% (2/37) of the infants were diagnosed with malignant diseases. One retroperitoneal embryonal rhabdomyosarcoma at 5 years old and one acute myeloid leukemia at 22 months of age. 32/37 (86.5%) children were healthy at the end of follow-ups (median 33 months, IQR 15.75-54.25 months). Our results showed that neoadjuvant platinum and paclitaxel combined chemotherapy was a feasible and safe choice for the management of patients with cervical and ovarian cancer during the second and third trimesters of gestation.

Real-world experience of olaparib as maintenance therapy in BRCA-mutated recurrent ovarian cancer

The primary objective of our study was to investigate the effectiveness and safety of olaparib maintenance therapy in patients with BRCA-mutated recurrent ovarian cancer in daily practice. The secondary objective of this study was to identify prognostic factors associated with prolonged progression-free survival (PFS) in such patients. We conducted a retrospective analysis of 40 patients who received olaparib maintenance treatment. Data on clinicopathological factors, oncological outcomes, and adverse events were obtained from medical records and analyzed. All patients had high-grade serous recurrent ovarian cancer with BRCA mutation and achieved complete or partial response to the most recent platinum-based chemotherapy. After a median follow-up of 14.3 months, the median PFS was 23.7 months (95% confidence interval, 14.1-33.4); however, the median overall survival was not reached. In the log-rank test, the PFS was significantly longer for patients with most recent platinum-free interval (PFI) ≥ 12 months, complete response to the last platinum-based chemotherapy, and less than three lines of previous chemotherapy (p = 0.005, p = 0.016, and p = 0.023, respectively). Most hematologic and non-hematologic adverse events were of grade 1 or 2, and the common adverse events were mostly related to myelosuppression. Olaparib maintenance treatment in BRCA-mutated recurrent ovarian cancer is effective and safe in clinical practice. Most recent PFI, response to the last platinum-based chemotherapy, and the number of previous chemotherapy lines were associated with PFS in patients with BRCA-mutated recurrent ovarian cancer.

Alpha-fetoprotein (AFP)-producing epithelial ovarian carcinoma (EOC): a retrospective study of 27 cases

The aim of the study was to investigate the relative risk factors associated with the prognosis and effective treatments of alpha-fetoprotein (AFP)-producing epithelial ovarian carcinoma (EOC). We presented three cases of AFP-producing EOC and performed a brief review to summarize the clinicopathological features and prognostic factors of 24 cases that have been previously reported. We evaluated the correlations among prognostic and clinical parameters, such as stage, pathology and chemotherapy regimens. In addition, a retrospective review of these 27 cases was conducted, and survival curves were estimated using the Kaplan-Meier method. The patients were aged between 23 and 77 years. The median overall survival was 10 months, and ten (37.04%) patients died within 18 months. We compared the overall mean survival times of all patients in different stages, and the results suggest that the postoperative pathological staging is hardly correlated with prognosis (P = 0.76). There was a correlation between pathology and prognosis (P = 0.0018). The mean survival time was longer for patients who had undergone chemotherapy than for those without chemotherapy (14.88 vs 0.65 months) (P < 0.0001). Moreover, although patients had a good response to the regimens for PEB and TC (P = 0.004), there was no significant difference between PEB and TC (P = 0.386). AFP-producing EOC is uncommon and regarded as an extremely malignant type of tumor. Patients with chemotherapy may have a longer survival time; additionally, PEB and TC may be an optimal selection for this kind of tumor. Further large-scale studies are needed to confirm our findings.

Response evaluation after neoadjuvant therapy: evaluation of chemotherapy response score and serological and/or radiological assessment of response in ovarian cancer patients

The chemotherapy response score (CRS) is a histopathological tool to evaluate response to neoadjuvant chemotherapy (NACT) in high-grade serous ovarian cancer (OC). We critically evaluated the clinical value of CRS and compared its predictive power to standard serological (CA125) and radiological response. A retrospective analysis of 277 OC patients, who received primary chemotherapy, was performed. CRS, serological, and radiological findings were correlated with progression-free (PFS) and overall survival (OS). CRS could be determined in 172 of 277 patients (62.1%). In patients with CRS3, a longer median PFS and OS was observed compared with CRS1/2 patients (31.2 vs. 18.9, P < 0.001; 55.0 vs. 36.1 months, P = 0.050). CA125 and radiological response evaluation were also predictive for PFS and OS. Patients with serological and radiological complete response showed longer PFS (23.0 vs. 14.4, P = 0.011; 21.4 vs. 9.6 months, P < 0.001) and OS (49.5 vs. 29.0, P = 0.003; 45.0 vs. 12.9 months, P < 0.001). Patients with pathological complete response (pCR) had the best median PFS (52.8 months), even compared with non-pCR CRS3 (27.8 months). In the total study cohort, serological, and radiological complete response was better at predicting PFS (hazard ratio 2.23 and 2.77). In this study, evaluation of response to chemotherapy by CRS was not superior to conventional methods (CA125 or radiology). Independent of the evaluation method, response to NACT was predictive of PFS and OS. We observed no added value for CRS as a prognostic marker. The clinical relevance of CRS should be discussed, as no therapeutic consequences result from CRS evaluation.

Incidence of and risk factors associated with lung metastases in newly diagnosed epithelial ovarian cancer with a look on prognosis after diagnosis: a population-based cohort study of the SEER database

Patients with lung metastases (LM) from epithelial ovarian cancer (EOC) (EOCLM) usually have a poor prognosis. However, there is no consensus on the optimal management of these patients. In this study, we aimed to take a look at the incidence of LM and factors associated with its occurrence as well as the prognosis in newly diagnosed EOC with LM on a population level. EOC patients diagnosed between the years 2010 and 2016 were identified from the Surveillance, Epidemiology, and End Results (SEER) program database. Multivariable logistic regression and multivariable Cox regression were used to investigate the factors that could predict the occurrence of and prognosis after diagnosis of EOC with LM. Of the 33,418 qualified EOC patients, 2240 (6.7%) were noted to have LMs at the time of EOC diagnosis. Higher T stage, N1 stage, advanced tumor grade, and elevated cancer antigen-125 levels were found to be associated with a higher risk of having LM at the time of EOC diagnosis. The median survival time after diagnosis with EOCLM was found to be 13.0 months (interquartile range: 3.0-34.0 months). Being unmarried and having mucinous histology were both associated with increased all-cause death risk from EOCLM. However, the primary tumor originated from the midline of ovaries, surgical management, and whether patient received chemotherapy or not predicted improved overall survival. The median survival time of patients was significantly longer for EOCLM cases managed surgically (31.0 months) versus those who did not have surgery (4.0 months), as well as EOCLM cases received chemotherapy (23.0 months) versus those who did not have chemotherapy (2.0 months). This retrospective cohort study showed that de novo LM was infrequent in EOC patients overall and when present predicted poor prognosis. The findings can be potentially useful in formulating for follow-up strategies, screening tools, and personalized interventions.

Neovagina creation methods in Müllerian anomalies and risk of malignancy: insights from a systematic review

This systematic review aims to provide a data synthesis about the risk of neovaginal cancer in women with Müllerian anomalies and to investigate the association between the adopted reconstructive technique and the cancer histotype. PubMed, MEDLINE, Embase, Scopus, ClinicalTrials.gov and Web of Science databases were searched from inception to March 1st, 2023. Studies were included if: (1) only women affected by Müllerian malformations were included, (2) the congenital defect and the vaginoplasty technique were clearly reported, (3) the type of malignancy was specified. Literature search yielded 18 cases of squamous cell carcinoma and two cases of vaginal intraepithelial neoplasia 3 (VAIN 3). Of these, 3 had been operated on according to the Wharton technique, 8 according to the McIndoe technique, 3 with a split-skin graft vaginoplasty, 2 according to the Davydov technique, 2 with a simple cleavage technique, 1 according to the Vecchietti technique and 1 with a bladder flap vaginoplasty. A total of 17 cases of adenocarcinoma and 1 case of high-grade polypoid dysplasia were also described. Of these, 15 had undergone intestinal vaginoplasty, 1 had been operated on according to the McIndoe technique and 1 had undergone non-surgical vaginoplasty. Finally, 1 case of verrucous carcinoma in a woman who had undergone a split-skin graft vaginoplasty, was reported. Although rare, neovaginal carcinoma is a definite risk after vaginal reconstruction, regardless of the adopted technique. Gynaecologic visits including the speculum examination, the HPV DNA and/or the Pap smear tests should be scheduled on an annual basis.

Modified intestinal isolation bag as promising tool in promoting bowel resumption after ovarian cancer cytoreductive surgery: a randomized clinical trial

Postoperative ileus (POI) impairs patient recovery, prolonging hospital stay after major surgery in ovarian cancer (OvCa) patients. Thus, intraoperative bowel isolation is expected to reduce manipulation-related impairment. The aim of this study was to investigate the impact of intraoperative intestinal isolation bag on POI in OvCa patients submitted to primary surgery. A randomized trial including patients managed with or without isolation bag during OvCa primary surgery was conducted. Patients were selected by consecutive randomization. Primary endpoints were the time between surgery and resumption of bowel motility (as passage of first/continued flatus), assessing of postoperative nausea or vomiting and return to regular diet. Secondary endpoint was the impact of intestinal isolation bag on length of hospitalization in the two groups. Ninety-two patients respecting inclusion criteria were eligible to be enrolled in the study (48 patients as Group 1 and 44 patients as Group 2). Thirty-eight (79.2%) patients, in which intraoperative isolation bag was used, experienced first/continued flatus within 3 days from surgery and they were susceptible to be discharged within 5 days, compared, respectively, to 34.3% of Group 2 (n = 15). Advantages were more evident in patients whose surgery took over 220 min (OR 0.02, CI 95% 0.001-0.57; p < 0.001) despite the type of surgical effort made. Despite the small sample size, our study showed that the use of intestinal isolation bag can reduce incidence of POI and length of stay in OvCa patients submitted to primary cytoreductive surgery.

Clinical characteristics and prognostic factors of stage IC ovarian clear cell carcinoma: a Surveillance, Epidemiology, and End Results (SEER) analysis

The study aimed to investigate the clinical characteristics and prognostic factors of stage IC ovarian clear cell carcinoma (OCCC). The Surveillance, Epidemiology, and End Results (SEER) database was accessed for medical records of patients with stage IC OCCC from 1992 to 2016. The clinical and prognostic features of stage IC OCCC from several therapeutic perspectives were identified with Kaplan-Meier method and Cox proportional hazards model. Totally, 1079 patients were enrolled for the analysis. The median age was 55 (range 24-91) years. 850 (78.8%) patients were treated with chemotherapy, 877 (81.3%) received lymph node (LN) dissection, and 20 (1.9%) underwent radiotherapy. LN dissection (P = 0.501) and chemotherapy (P = 0.130) did not significantly impact cancer-specific survival (CSS). Among patients younger than 45 years, 23 received fertility-sparing surgery (FSS). No significant difference in CSS was observed between the FSS and non-FSS group (P = 0.523). Bilateral tumor (P < 0.001) and larger tumor size (P = 0.010) were significantly and independently associated with poor CSS. Older age (P = 0.001), bilateral tumor (P < 0.001), and larger tumor size (P = 0.005) were significantly and independently associated with poor overall survival (OS), while LN dissection (P = 0.005) was significantly and independently associated with better OS. Significant differences in CSS (P = 0.005) and OS (P < 0.001) were observed between the low- and high-risk groups, which were divided by median risk score. LN dissection and chemotherapy did not significantly impact CSS, while LN dissection was an independent prognostic factor for OS. Convincing evidence from clinical trials with a large number of patients are further required to develop treatment guidelines.

Malignant struma ovarii: surgical, histopathological and survival outcomes for thyroid-type carcinoma of struma ovarii with recommendations for standardising multi-modal management. A retrospective case series sharing the experience of a single institution over 10 years

Struma ovarii is rare, accounting for 0.3-1% of ovarian tumours. Malignant transformation may occur, most often into papillary thyroid carcinoma. There is a paucity of data pertaining to malignant struma ovarii. This paper shares a decade of experience of a single institution in the management of this rare ovarian cancer, exploring the characteristics of this tumour and suggesting a standardised approach to treatment and follow-up. All patients treated for malignant struma ovarii within a large cancer centre over one decade were identified and data collected retrospectively on presentation, diagnosis, management, follow-up and survival outcomes. A literature review was also undertaken. Eleven cases of malignant struma ovarii were managed in the Oxford Cancer Centre between 2010 and 2019, 6 of which were of papillary thyroid carcinoma sub-type. No cases were correctly diagnosed pre-operatively. All patients had stage I disease and were managed surgically-but with variation in radicality. Patients identified as high-risk based on final histopathology underwent additional thyroidectomy and radio-active iodine ablation therapy. One case of synchronous malignancy of the thyroid gland proper was identified. No disease recurrence occurred. Malignant struma ovarii present a diagnostic challenge. Multi-disciplinary team (MDT) input is essential. Unilateral salpingo-oophrectomy may be adequate if stage I; reserving more radical surgery for advanced disease. Histopathological risk-stratification should be used to identify those most likely to benefit from adjuvant thyroid-targeting therapies. Patients require follow-up, anticipating an overall good prognosis.

Transferability of the early-stage ovarian malignancy (EOM) score: an external validation study that includes advanced-stage and metastatic ovarian cancer

To validate the diagnostic performance of the Early-stage Ovarian Malignancy (EOM) score in an external dataset that includes advanced-stage and metastatic ovarian cancer. The data from two cross-sectional cohorts were used in the statistical analysis. The development dataset of the EOM score was collected in Phrapokklao Hospital between September 2013 and December 2017. The validation dataset was collected in Maharaj Nakorn Chiang Mai Hospital between April 2010 and March 2018. The internal and external performance of the EOM score was evaluated in terms of discrimination via area under the receiver-operating characteristic curve (AuROC) and calibration. There were 270 and 479 patients included in the development and validation datasets, respectively. The prevalence of ovarian malignancy was 20.0% (54/270) in the development set and 30.3% (145/479) in the validation set. The EOM score had excellent discriminative ability in both the development and validation sets (AuROC 88.0 (95% CI 82.6, 93.9) and 88.0 (95% CI 84.3, 91.4), respectively). The EOM score also showed good calibration in both datasets. The EOM score had consistent diagnostic performance in the external validation data. It is recommended for use as a triage tool in patient referrals instead of the RMI in settings where experienced sonographers are not available.

Concordance of laparoscopic and laparotomic peritoneal cancer index using a two-step surgical protocol to select patients for cytoreductive surgery in advanced ovarian cancer

The aim of our study was to assess concordance of staging laparoscopy and cytoreductive surgery (CRS) peritoneal cancer index (PCI) when applying a two-step surgical protocol. We also aimed to evaluate the accuracy of diagnostic laparoscopy to triage patients for complete cytoreduction, and to define optimal time between staging laparoscopy and CRS. We designed a retrospective review of prospectively collected data from patients with advanced ovarian cancer who underwent a diagnostic laparoscopy followed by a CRS a few weeks later (two-step surgical protocol), from January 2010 to April 2019. Only patients selected for complete cytoreduction, and with available PCI score from both surgeries were included. PCI concordance was assessed using intraclass correlation coefficient (ICC). During the study period 543 patients underwent a laparoscopic staging for ovarian carcinomatosis. Among them, 43 patients fulfilled inclusion criteria. ICC between laparoscopic and laparotomic PCI was 0.54. After applying the linear regression equation: laparoscopic PCI + 0.2 x [days between surgeries] + 2, ICC increased to 0.79. Completeness cytoreduction score and laparoscopic PCI were significantly associated (OR 1.27, 95% CI 1.03-1.57, p = 0.03). AUC of laparoscopic PCI to predict complete cytoreduction was 0.90. Concordance between laparoscopic PCI assessment and PCI score at the end of CRS is fair within a two-step surgical management. Laparoscopic assessment underestimates final PCI score by two points, and this difference increases with the delay between both surgeries. Diagnostic laparoscopy can adequately select patients for CRS, and optimal time to perform it is no more than 10 days after laparoscopy.

A history of cesarean section and future maternal long-term risk for neoplasms: a population-based cohort study

Mode of delivery has long-term implications on the mother, including recent data regarding the level of transmission of fetal microchimeric cells (FMc) and their possible effect on cancer development. We aimed to evaluate the association between cesarean section (CS) and future risk for neoplasms. A population-based cohort analysis comparing the long-term risk for neoplasms between patients that delivered only by CS to those that delivered only vaginally (VD). Neoplasms were pre-defined based on ICD-9 codes. Deliveries occurred between the years 1991-2017 in a tertiary medical center. Kaplan-Meier survival curves were used to compare the cumulative incidence of neoplasms and Cox proportional hazards models were constructed to control for confounders. During the study period 105,992 patients met the inclusion criteria; 14150 (13.4%) of patients had only CS and 91842 (86.6%) had VD (comparison group). The CS group had significantly higher incidence of benign and malignant neoplasms (4.73 per 1000 patient-years versus 3.88 per 1000 patient-years, OR = 1.26, 95% CI 1.16-1.37; p = 0.001; 2.19 per 1000 patient-years of follow up versus 1.93 per 1000 patient-years, OR = 1.16, 95% CI 1.03-1.31; p = 0.013). Specifically, the CS group had higher incidence of uterine cancer (1.2 versus 0.06 per 1000 patient-years, OR = 1.97, 95% CI 1.14-3.39; p = 0.013). The cumulative incidence of benign, malignant and uterine neoplasms was significantly higher in the CS group (Log rank test p = 0.001; 0.036 and 0.014; respectively). Importantly, no significant association was found with breast and ovarian malignancies." When performing a Cox regression model controlling for confounders, the risk for malignancy-related hospitalizations remained significant (adjusted HR = 1.22, 95% CI 1.01-1.48; p = 0.031) but not for uterine cancer (adjusted HR = 1.6, 95% CI 0.9-2.8; p = 0.103). Our findings provide support to linkage between delivery by cesarean section and future maternal malignancy.

Survival benefit of vaginectomy compared to local tumor excision in women with FIGO stage I and II primary vaginal carcinoma: a SEER study

The effectiveness of vaginectomy compared to that of local tumor excision (LTE) for the International Federation of Gynecology and Obstetrics (FIGO) stage I and II vaginal carcinoma is unclear. We aimed to clarify if the effectiveness of vaginectomy is comparable to that of LTE in the real world. We retrospectively evaluated data of patients with primary vaginal carcinoma registered in the Surveillance, Epidemiology, and End Results Program (SEER) database from 2004 to 2016. The multivariate Cox proportional hazards models and Fine-Gray competing risk models were used to estimate the overall survival (OS) and disease-specific survival (DSS) after propensity score matching. Of the 533 patients with FIGO stage I and II primary vaginal carcinoma, 243 and 290 patients were treated with vaginectomy and LTE, respectively. Vaginectomy was significantly associated with improved OS [unadjusted hazard ratio (HR) = 0.70, 95% confidence interval (CI) 0.53-0.95, P = 0.020; adjusted HR = 0.63, 95% CI 0.46-0.87, P = 0.005] and DSS [unadjusted subdistribution HR (sHR) = 0.75, 95% CI 0.52-1.07, P = 0.115; adjusted sHR = 0.65, 95% CI 0.44-0.97, P = 0.036]. Age, marital status, histology type, FIGO stage, chemotherapy, and lymph node metastases were significant prognostic factors of survival. Moreover, radiotherapy did not influence the effectiveness of vaginectomy. Subgroup and sensitivity analysis confirmed the consistent beneficial effectiveness of vaginectomy. Compared with LTE, vaginectomy results in significantly prolonged survival in patients with FIGO stage I and II primary vaginal carcinoma. Thus, it can be the preferred treatment for FIGO I and II vaginal cancer regardless of radiotherapy status.

Utilization of sentinel lymph node biopsy in the early ovarian cancer surgery

Sentinel lymph node (SLN) biopsy has been incorporated into surgical care for many malignancies; however, the utility has not been examined in ovarian cancer. This study examined population-level trends, characteristics, and outcomes related to SLN biopsy in early stage ovarian cancer. This is a retrospective cohort study querying the National Cancer Institute's Surveillance, Epidemiology, and End Result Program from 2003-2018. The study population consisted of 11,512 women with stage I ovarian cancer who had adnexectomy-based surgical staging including lymph node evaluation. Exposure allocation was based on SLN biopsy use. Main outcomes measured were (i) trends and characteristics associated with SLN biopsy use, assessed by multivariable logistic regression model, and (ii) overall survival assessed with inverse provability of treatment weighting propensity score. SLN biopsy was performed in less than 1% of study population. In a multivariable analysis, recent surgery (2011-2018 versus 2003-2010, odds ratio [OR] 1.64, 95% confidence interval [CI] 1.03-2.59), smaller tumor size (< 10 versus ≥ 10 cm, OR 3.07, 95% CI 1.20-7.84), and East registry area (OR 2.74, 95% CI 1.73-4.36) remained independent characteristics for SLN biopsy use. In a propensity score weighted model, 5-year overall survival rate was 90.5% for the SLN biopsy-incorporated group and 88.6% for the lymphadenectomy group (hazard ratio 0.96, 95% CI 0.53-1.73). SLN biopsy was rarely performed for early ovarian cancer surgery during the study period with insufficient evidence to interpret the survival effect. SLN biopsy in early ovarian cancer appears to be in early development phase, warranting further study and careful evaluation to assess feasibility and oncologic outcome.

A machine learning approach applied to gynecological ultrasound to predict progression-free survival in ovarian cancer patients

AbstractIn a growing number of social and clinical scenarios, machine learning (ML) is emerging as a promising tool for implementing complex multi-parametric decision-making algorithms. Regarding ovarian cancer (OC), despite the standardization of features that can support the discrimination of ovarian masses into benign and malignant, there is a lack of accurate predictive modeling based on ultrasound (US) examination for progression-free survival (PFS). This retrospective observational study analyzed patients with epithelial ovarian cancer (EOC) who were followed in a tertiary center from 2018 to 2019. Demographic features, clinical characteristics, information about the surgery and post-surgery histopathology were collected. Additionally, we recorded data about US examinations according to the International Ovarian Tumor Analysis (IOTA) classification. Our study aimed to realize a tool to predict 12 month PFS in patients with OC based on a ML algorithm applied to gynecological ultrasound assessment. Proper feature selection was used to determine an attribute core set. Three different machine learning algorithms, namely Logistic Regression (LR), Random Forest (RFF), and K-nearest neighbors (KNN), were then trained and validated with five-fold cross-validation to predict 12 month PFS. Our analysis included n. 64 patients and 12 month PFS was achieved by 46/64 patients (71.9%). The attribute core set used to train machine learning algorithms included age, menopause, CA-125 value, histotype, FIGO stage and US characteristics, such as major lesion diameter, side, echogenicity, color score, major solid component diameter, presence of carcinosis. RFF showed the best performance (accuracy 93.7%, precision 90%, recall 90%, area under receiver operating characteristic curve (AUROC) 0.92). We developed an accurate ML model to predict 12 month PFS.

The worsening impact of programmed cell death ligand 1 in ovarian clear cell carcinomas

To investigate the clinical significance of programmed cell death ligand 1 (PD-L1) expression in ovarian clear cell carcinoma (CCC). Patients with CCC who underwent primary surgery at our hospital between 1984 and 2014 were enrolled in this study. PD-L1 and mismatch repair (MMR) protein expression in tumor cells, tumor-infiltrating lymphocytes (TILs), including cluster of differentiation (CD) 8, CD4, forkhead box P3 (FOXP3), programmed cell death 1 (PD-1), and BAF250a, were evaluated using immunohistochemistry. The association between PD-L1 expression, clinicopathological features, prognosis, and expression of several proteins was investigated. Of the 125 patients with CCC, 17 had negative PD-L1 and 108 had positive PD-L1. Patients with positive PD-L1 expression showed a lower response to chemotherapy (p = 0.01). In addition, patients with positive PD-L1 showed worse progression-free survival (PFS, p = 0.01) and overall survival (OS, p = 0.01) than that in patients with negative PD-L1 expression. Multivariate analyses for PFS and OS showed that PD-L1 expression was an independent prognostic factor for PFS (hazard ratio [HR] 7.81, p < 0.01) and OS (HR 12.90, p < 0.01). PD-L1 expression was not associated with the expression of several TILs or proteins. The expression of PD-L1 was related to a lower response to chemotherapy and worse prognosis in CCC. These results may be useful for the development of new treatments.

Efficacy and safety of an adsorbent and anti-oxidative vaginal gel on CIN1 and 2, on high-risk HPV, and on p16/Ki-67: a randomized controlled trial

Abstract Purpose The effect of SAM vaginal gel, a medical device containing adsorptive silicon dioxide and antioxidative sodium selenite and citric acid, on histologically-proven cervical intraepithelial neoplasia type 2 (CIN2) as well as p16 positive CIN1, and on the presence of the onco-marker p16 was investigated. Methods 216 women aged 25–60 years were randomized to either receive an intravaginal daily dose of SAM gel for three 28-day periods, or be followed-up without intervention. The primary endpoint was efficacy, defined as a combined histological and cytological regression. At baseline and after 3 months participants had: a guided biopsy including p16 immunohistochemical (IHC) staining, only if a lesion was visible at colposcopy; a cervical smear for cytology, high-risk human papillomavirus (hr-HPV) and a p16/Ki-67 test. At 6 months a further cytology and p16/Ki-67 test was performed. Results Regression of CIN lesions was observed in 78 out of 108 patients (72.2%) in the SAM gel arm and in 27 out of 108 patients (25.0%) in the control arm. Similarly, the change in the p16/Ki-67 cytological test status was significantly in favor of the treatment arm. The prevalence of hr-HPV decreased significantly (p &lt; 0.001) in the treatment arm, from 87.0% to 39.8%, while it slightly increased in the control arm, from 78.7% to 83.3%. At 6 months the cytological regression in the treatment group and the highly significant effect on p16/Ki-67 was still present. Conclusion SAM vaginal gel enhances the regression of cervical lesions and clears hr-HPV and p16/Ki-67 in smears significantly, thus offering an active non-destructive management to prevent cervical cancer. Trial registration number ISRCTN11009040, date of registration: 10/12/2019; https://doi.org/10.1186/ISRCTN11009040; retrospectively registered.

Pre-operative mapping and structured reporting of pelvic endometriotic lesions on dynamic ultrasound and its correlation on laparoscopy using the #ENZIAN classification

The objective of this study was to evaluate and compare the diagnostic performance of ultrasonography (USG) assessment using structured reporting with intraoperative laparoscopic assessment in deep infiltrating endometriosis (DIE) using the recent update of the #ENZIAN classification. This was a retrospective study conducted in Tertiary Multi-disciplinary Endometriosis Care Hospital over a period of 8 months which included 50 patients who underwent a planned laparoscopic endometriosis excisional surgery after a dedicated USG assessment using International Deep Endometriosis Analysis (IDEA) protocol and #ENZIAN score (updated ENZIAN classification), between Feb 2021 and Sept 2021 at Apollo Hospitals, Hyderabad. The pre-operative USG findings were reported in a structured reporting format and intraoperative findings were classified using the standard #ENZIAN classification. No prospective interventions were done. A review of pre-operative ultrasound and laparoscopic findings as per the #ENZIAN was done. Sensitivity and the negative predictive value of ultrasound were 86% and 84.2% for peritoneal lesions, 97% and 93.3% for left ovarian lesions, 93% and 91.6% for right ovarian lesions, 91% and 84% for left tubal lesions, 90% and 86.3% for right tubal lesions, 93% and 75% for uterosacral ligaments, 93.3% and 97% for rectal lesions and sensitivity and negative predictive values were 100% for rectovaginal lesions, adenomyosis, and ureteric lesions as confirmed on laparoscopy. Dynamic ultrasound assessment with a structured report based on IDEA protocol and #ENZIAN score is accurate for mapping of pelvic endometriosis in all forms, and it correlates with laparoscopic findings, thus helps surgeon for better planning and providing a road map for surgeons. From a clinical perspective, a uniform and shared reporting system across imaging and therapeutic modalities will simplify communication, improving patient management by conservative or surgical treatments, avoiding multiple repeat surgeries, and improving quality of treatment.

The potential feasibility of nab-paclitaxel as the first-line chemotherapy for ovarian cancer: clinical development and future perspectives

Optimal first-line chemotherapy regimens are crucial for epithelial ovarian cancer (EOC) treatment. Nab-paclitaxel has showed its considerable survival and low toxicity profiles in first-line treatment for three solid tumors and is recommended as a treatment for recurrent EOC. We focus on clinical efficacy and safety outcomes of nab-paclitaxel in current clinical studies of EOC treatment and aim to explore the potential feasibility of nab-paclitaxel as the first-line treatment for EOC. We searched for eligible studies up to January 2020 in Pubmed. Outcomes of interests included drug regimes, objective response rate (ORR), median progression free survival (PFS), median overall survival (OS) and main adverse events to determine feasibility of nab-paclitaxel. This review included nine eligible studies. One study about nab-paclitaxel with carboplatin as first-line therapy in ten cases after hypersensitivity to paclitaxel had an ORR of 100%, median PFS of 16.7 months and median OS of 65.4 months. Evidence of nab-paclitaxel activity in platinum-sensitive EOC demonstrated an ORR of 64%, a median time to response of 1.3 months and PFS of 8.5 months. The ORR, median PFS and median OS range in patients with recurrent platinum-resistant EOC from 23%-72%, 4.0-8.5 months, 16.8-17.4 months, respectively. All studies demonstrated manageable toxicity profile in EOC patients. Nab-paclitaxel presents potentials as the first-line chemotherapy for considerable survival and safety in EOC compared to conventional paclitaxel. However, there is no prospective trial in EOC so far. Therefore, more studies about nab-paclitaxel are needed.

Irisin/FNDC5 inhibits the epithelial–mesenchymal transition of epithelial ovarian cancer cells via the PI3K/Akt pathway

This study explored the role of irisin/fibronectin type III domain-containing protein 5 (FNDC5) in epithelial ovarian cancer and investigated its underlying mechanisms. Immunohistochemistry was performed to analyze the expression of irisin/FNDC5 in epithelial ovarian cancer and normal ovarian tissues. Cell Counting Kit-8, transwell, and wound-healing assays were performed to examine the effect of irisin on the viability, migration, and invasion of ovarian cancer cells, respectively. Western blotting was used to detect the changes of epithelial-mesenchymal transition (EMT)-related proteins and phosphatidylinositol 3-kinase (PI3K)/Akt pathway proteins. Ovarian cancer cells were treated in vitro with the PI3K agonist (740Y-P) in combination with irisin to explore the mechanism of irisin in ovarian cancer. The expression of irisin/FNDC5 in epithelial ovarian cancer tissue was significantly higher than that in normal ovarian tissues, and the expression in late stage patients with lymph node metastasis was lower than that in early stage patients without metastasis. Irisin inhibited the proliferation, invasion, and migration of epithelial ovarian cancer cells, down-regulated phosphorylated Akt, and inhibited EMT progression. The PI3K agonist, 740Y-P, partially reversed the effects of irisin on the invasion, migration, and EMT of ovarian cancer cells. These findings show that irisin/FNDC5 was highly expressed in ovarian cancer tissues, which may regulate the EMT through the PI3K/Akt signaling pathway and inhibit the proliferation, invasion, and migration of epithelial ovarian cancer.

Risk factors for and prognosis of carboplatin-related hypersensitivity in patients with epithelial ovarian cancer

We aimed to identify the predictive risk factors for carboplatin-related hypersensitive reactions (HRs) and investigate their impact on survival outcomes in patients with epithelial ovarian cancer (EOC). This retrospective study included 222 patients with EOC who received carboplatin infusion between July 2016 and November 2019. We compared the clinicopathologic characteristics and survival outcomes between carboplatin-related hypersensitivity and non-hypersensitivity groups. Hypersensitivity data were classified using the Common Terminology Criteria for Adverse Events (CTCAE) version 5.0, categorizing grades from 1 to 5 as mild/moderate/severe/life-threatening/death. Multiple logistic regression analysis was used to analyze risk factors of HRs. The Cox proportional hazard regression model was used to determine the factors of being significantly associated with overall survival. Of the 222 patients, eight exhibited HRs (incidence rate, 3.6%). All HRs were of grade 3 or 4 (life-threatening). In all cases, a desensitization protocol was followed. Advanced stage (III or IV) (P = 0.022), previous history of carboplatin use (P < 0.001), and recurrent ovarian cancer (P = 0.001) were significantly associated with HR to carboplatin. Multivariate logistic analysis showed that a previous history of carboplatin was the only independent risk factor for carboplatin-related hypersensitivity (OR, 20.19; 95% CI 1.22 - 3034.10; P = 0.034). However, HR to carboplatin did not influence the overall survival (P = 0.526). In EOC patients, prior use of carboplatin was an independent risk factor for carboplatin-related HRs; HRs to carboplatin did not influence the overall survival. Clinicians should not underestimate the possibility risk of carboplatin HSRs when re-administrating carboplatin in EOC patients.

Subfertility, use of fertility treatments and BRCA mutation status and the risk of ovarian cancer

The objective of the study is to evaluate the possible association between history of subfertility, fertility treatments, BRCA mutations and the risk of ovarian cancer. This Israeli National Case-Control study included 1269 consecutive ovarian cancer cases and 2111 individually matched healthy controls. All participants were interviewed and molecular analysis of BRCA mutations were performed to 896 cases. The main outcome measure was reported history of subfertility and exposure to fertility treatments. The rate of reported subfertility was 15.1% and 14.3% in ovarian cancer cases and controls, respectively. However, subfertility was more prevalent in cases with borderline ovarian cancer (but not for invasive ovarian cancer cases) than controls. Multivariate conditional logistic regression revealed that the risk of borderline ovarian cancer was elevated in both women treated for subfertility and those that were not treated for subfertility, (OR = 1.74; 95% CI 0.9-3.36 and OR = 1.79; 95% CI 0.98-3.26, respectively). In non-carriers of BRCA1/2 mutations, fertility treatments were associated with a decreased risk of invasive ovarian cancer while a significant increased risk of borderline ovarian cancer was observed (OR = 2.92, 95%CI 1.67-5.10). Reported subfertility and exposure to fertility treatments were associated with borderline but not with invasive ovarian tumors. This association was more prominent in women who are non-carriers of a BRCA mutation.

Patterns of use and outcomes of adjuvant bevacizumab therapy prior to regulatory approval in women with newly diagnosed ovarian cancer

We used real-world claims data to assess the utility of the relatively novel therapeutic bevacizumab in patients with newly diagnosed ovarian cancer in the United States after release of clinical data but prior to FDA approval. We used the IQVIA Pharmetrics Plus commercial claims database to identify women with a new diagnosis of ovarian cancer who underwent primary surgery or neoadjuvant chemotherapy followed by interval surgery from 2006 to 2018. We calculated the rate of use of bevacizumab, and the relative frequency of hospital and emergency department (ED) admissions. Treatment-related toxicities, and time to second line chemotherapy were calculated. Among 8923 women who met study parameters, 533 (6.0%) received bevacizumab. The rate of use increased over time from 1.5% in 2006 to 7.0% in 2017 (P < 0.001), with a peak of 8.6% in 2011. The use was lowest in those ≥ 70 years old (2.8%), and in the West (4.5%), and was unaffected by number of comorbidities. Over one third (35.1%) received bevacizumab for less than 3 months, and 15.9% remained on it for greater than 13 months. Bevacizumab use was not associated with hospitalization or ED admission. Toxicities included hypertension (15.0%), kidney damage (6.8%), bleeding (3.8%), venous thrombo-embolism (2.3%) and fistula (1.1%). Time from initiation of first line chemotherapy to initiation of second line therapy was 19.9 months without bevacizumab and 22.6 months with bevacizumab use. Real-world patterns of upfront bevacizumab use prior to FDA approval in 2018 differed significantly from trial data.

Laparoscopic nerve-sparing radical hysterectomy without uterine manipulator for cervical cancer stage IB: description of the technique, our experience and results after the era of LACC trial

The aim of this study is to evaluate surgical data and oncological outcome of laparoscopic nerve-sparing radical hysterectomy without uterine manipulator for cervical cancer stage IB, over the last 8 years. This retrospective study includes 32 patients with cervical cancer Figo stage (2009) IB who underwent laparoscopic nerve-sparing radical hysterectomy without using any kind of uterine manipulator. Patients were eligible if they had squamous cell carcinoma, adenocarcinoma, or adeno-squamous carcinoma, and no para-aortic lymph node involvement by imaging or after frozen section. The median value and range were assessed for operative outcomes and relapse rate and disease-free survival rate were evaluated using the Kaplan-Meier method. In the study, 32 patients were included and among them 27 women were stage IB1 (18 cases with tumor size 2-4 cm) and 5 women stage IB2 (Figo stage 2009). The median age of patients was 50.5 years (range 31-68) and median body mass index (B.M.I) was 25.3 kg/m Laparoscopic nerve-sparing radical hysterectomy without uterine manipulator is feasible and safe surgical procedure for cervical cancer with acceptable surgical and oncological outcomes in the hands of well-trained and experienced laparoscopic surgeons. Our retrospective study reveals better oncological outcome compared to other studies on the minimally invasive approach, where uterine manipulator was routinely used and no vaginal sealing of the tumor was made.

Comparison of the survival outcome of neoadjuvant therapy followed by radical surgery with that of concomitant chemoradiotherapy in patients with stage IB2–IIIB cervical adenocarcinoma

To compare the survival outcome of neoadjuvant therapy (NAT) (chemotherapy or chemotherapy and intracavitary brachytherapy (ICBT) followed by radical surgery and of concomitant chemotherapy and radiotherapy (CCRT) in patients with locally advanced cervical adenocarcinoma and identify predictors of cervical adenocarcinoma. We retrospectively reviewed our medical records of cervical adenocarcinoma patients treated with either NAT + surgery or CCRT in our institution from January 2013 to December 2017. The patients were treated with two-dimensional radiotherapy or three-dimensional-conformal or intensity-modulated radiotherapy combined with intracavitary brachytherapy. The regimen of concomitant chemotherapy was weekly cisplatin. The neoadjuvant chemotherapy (NACT) was paclitaxel plus cisplatin. The primary end points were overall survival (OS) and progression-free survival (PFS). We enrolled 121 patients. There were 42 (34.7%) patients in the NAT + surgery group and 79 (65.3%) in the CCRT group. After univariate multivariate analysis, NAT was an independent predictor of OS (p = 0.008) and PFS (p = 0.006). After propensity score matching, the 5-year OS rates in the NAT + surgery and CCRT groups were 25% and 4%, respectively (p = 0.00014), and the 5-year PFS rates were 25% and 4%, respectively (p = 0.00015). Subgroup analysis showed that the 5-year OS and PFS rates in the NACT + surgery and CCRT groups were both 20% and 8%, respectively (p = 0.015). Compared with CCRT, NAT followed by radical surgery had better OS and PFS in locally advanced cervical adenocarcinoma. In subgroup analysis, OS and PFS were longer for NACT + surgery than for CCRT.

Severe cervical inflammation and high-grade squamous intraepithelial lesions: a cross-sectional study

Inflammation has been reported as a facilitator in cervical oncogenesis, but the correlation between inflammation and cytological abnormality remains uncertain. The aim of this study was to investigate the correlation between inflammation and cytological abnormality. ThinPrep cytological test (TCT) was used to detect cervical cytological abnormalities and inflammation degrees of 46,255 women in this prospective cross-sectional study. Histopathological examination was used to define the cervical intraepithelial neoplasia (CIN) in patients with cervical cytological abnormalities. The study revealed that 8.87% (4102/46,255) of TCT results had cytological abnormalities. The 4102 included cases were classified as the case group, including atypical squamous cells (ASC), low-grade squamous intraepithelial lesions (LSIL) and high-grade squamous intraepithelial lesions (HSIL). Women with negative intraepithelial lesion or malignancy (NILM) were classified as the control group. About 88.83% (3644/4102) of women with cytological abnormalities showed inflammations. The rate of severe inflammation was significantly higher in the case group than the control group (23.86% vs. 2.0%, P = 0.000). Our results also showed that patients with severe inflammation had a significantly increasing incidence of cytological abnormality by 12.598 times and elevated the risk of HSIL by 756.47 times, compared to the inflammation negative group. Severe inflammation was positively related to HSIL. Patients with severe cervical inflammation should be given more follow-ups and regular examinations and treated more carefully than those with mild or no inflammation.

Does a pre-operative conization improve disease-free survival in early-stage cervical cancer?

Ever since the recent findings showing the lack of benefit of minimally invasive surgery (MIS) versus open surgery in early-stage cervical cancer, gynecologists have tried to explain these results. The primary objective of our study was to assess the impact of pre-operative conization on disease-free survival (DFS) in early-stage cervical cancer. The secondary objective was to analyze the peri-operative morbidity associated with a pre-operative conization. All patients undergoing a surgical management for early-stage squamous carcinoma or adenocarcinoma cervical cancer (IA1, IA2, IB1 and IB2 FIGO 2018) at a French university hospital from 2004 to 2018 were retrospectively included. We examined the association between conization and DFS using a Cox regression model. We also analyzed the morbidity associated with pre-operative conization. 48.4% (44/91) of the patients had a pre-operative conization (defined by a conization up to 90 days prior to surgery). 86.8% underwent MIS. There was a non-significant increase in the DFS with one patient presenting a recurrence in the conization group (2.3%) and six (12.8%) in the no conization group (log rank = 0.09). In univariate analysis, conization, definitive FIGO stage and pre-operative tumor size were associated with DFS (p < 0.2). Only pre-operative tumor size was significantly associated with DFS in multivariate analysis. There was a non-significant increase of adverse events in the conization group (43.2% in the conization group versus 23.4%, p = 0.06). Conization, through a reduction of tumor size, could improve DFS. Carefully selected patients could still benefit from minimally invasive surgery.

Prevalence and distribution of human papillomavirus genotypes in cervical intraepithelial neoplasia in China: a meta-analysis

Abstract Background and aim Data on type-specific human papillomavirus (HPV) are needed to investigate HPV-based screening tests and HPV vaccines. However, Chinese relevant data are insufficient. Therefore, this meta-analysis aimed to summarize and demonstrate the prevalence and distribution of HPV genotypes in cervical intraepithelial neoplasia (CIN) and compensate for the shortage of HPV vaccines in China. Methods The Medline, Embase, and the Cochrane Library databases, as well as references cited in the selected studies, were systematically searched for studies investigating the prevalence and distribution of HPV genotypes between January 2000 and April 2019 in China. Results A total of 8 studies were identified, which comprised 2950 patients with CIN1 and 5393 with CIN2/3. The overall HPV infection rate was 84.37%. The HPV infection rate was significantly higher in the CIN2/3 group (87.00%) than in the CIN1 group (79.56%) (χ2 = 80.095, P &lt; 0.001). The most common HPV types in CIN1 in order of decreasing prevalence were as follows: HPV52 (20.31%), HPV16 (16.81%), HPV58 (14.44%), HPV18 (6.44%), and HPV53 (5.76%). However, in the CIN2/3 group, HPV16 (45.69%) was the predominant type, followed by HPV58 (15.50%), HPV52 (11.74%), HPV33 (9.35%), and HPV31 (4.34%). Conclusions This study suggested that HPV16, HPV52, and HPV58 were the top three types of CIN in China. The findings might provide a reference for future HPV-based cervical cancer screening tests, treatment of HPV infection, and application of HPV vaccines in China.

Evaluation of the accuracy of colposcopy in detecting high-grade squamous intraepithelial lesion and cervical cancer

The primary aim of this study was to evaluate the diagnostic accuracy of colposcopy in identifying high-grade squamous intraepithelial lesion or worse (HSIL+) and the characteristic performance of colposcopic images with various severity levels of cervical lesions. The medical records from 1828 women who underwent colposcopy at Affiliated Hospital of Tongji University from February 2016 to March 2019 were reviewed. Human papilloma virus (HPV) GenoArray test kit (HybriBio Ltd) and Thinprep cytologic test (TCT, Hologic, USA) were used to perform HPV genotyping and cytology. All colposcopic images were collected from the standard-of-care colposcope (Leisegang 3ML LED) and evaluated based on the 2011 International Federation of Cervical Pathology and Colposcopy (IFCPC) Colposcopy Standards. The linear by linear association, Pearson χ The consistency between colposcopy and biopsy pathology was 59.35% with the moderate strength of kappa coefficient of 0.464. The sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of colposcopy and cytology for HSIL+ were 56.29%, 93.82%, 77.47%, 85.04% and 37.13%, 98.49%, 90.29%, 80.58%, respectively. The colposcopic features of HSIL+ were as follows: (1) thick or bulgy acetowhite epithelium with sharp border; (2) completely nonstained of Lugol's iodine; (3) type III/IV/V of gland openings; (4) punctation or atypical vessels. The data and findings herein provide the resource for evaluating the diagnostic value of colposcopy, and suggested that the accuracy of colposcopy is required to be further improved.

The value of microendoscopy in the diagnosis of cervical precancerous lesions and cervical microinvasive carcinoma

Cervical cancer is still one of the main causes of death in females. Conventional diagnostic tools such as colposcopy are still unsatisfactory, so accurate diagnostic tools for cervical diseases are needed. Therefore, the purpose of this study was to perform a clinical study to evaluate the value of microendoscopic imaging systems in the diagnosis of cervical precancerous lesions and cervical microinvasive carcinoma (MIC). Totally 106 patients ranging in age from 23 to 67 years were recruited. All patients had abnormal thin-layer cytology (TCT) results (≥ low-grade squamous intraepithelial lesions) and high-risk human papillomavirus (HPV) positivity. Each patient was first subjected to ordinary colposcopy, followed by microendoscopy and biopsy. All results of the colposcopy and microendoscopy images were compared to the histopathological diagnosis. Characteristics of pathological blood vessels were easily distinguished by microendoscopy compared with ordinary colposcopy. The diagnostic agreement rate of microendoscopy with the pathological diagnosis was higher (95.3%) than that of ordinary colposcopy (37.7%) (weighted kappa = 0.863, P < .01). When diagnosing HSIL and more advanced disease, the sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and accuracy of the microendoscopic diagnosis were significantly higher than those of ordinary colposcopy (97.6 and 38.1%), (95.5 and 63.6%), (98.8 and 80.0%), (91.3 and 21.2%) and (97.7 and 43.4%), respectively. This study shows that microendoscopy has important value in the diagnosis of cervical lesions which can provide real-time diagnosis in vivo without staining, particularly for lesions that are not sensitive to acetic acid staining.

Postoperative comparison of laparoscopic radical resection and open abdominal radical hysterectomy for cervical cancer patient

There are limited data regarding postoperative complications and autoimmune reactions caused by surgery in early-stage cervical cancer patients who underwent laparoscopic radical resection (LRR). This study aimed to investigate the therapeutic effect of LRR of cervical cancer patients and its effect on cytokines. 168 patients with cervical cancer were enrolled. The patients were divided into open group and laparoscopic group according to the random number table method, with 84 cases in each group. The surgical-related indexes and the incidence of complications of the two groups were observed, and the IFN-γ, TNF, and IL-1/2/4/6/8/10/12 levels in peripheral blood were compared before and after surgery in both groups. The operation time of the patients in the laparoscopic group was significantly shorter than that in the open group (119.56 ± 45.26 vs. 206.36 ± 54.39, P < 0.01). The intraoperative blood loss in the laparoscopic group was significantly less than that in the open group (155.29 ± 57.58 vs. 529.58 ± 162.4, P < 0.01). The postoperative visual analog scale (VAS) score was also significantly lower than that in the open group (3.65 ± 0.88 vs. 6.32 ± 1.12, P < 0.01). There was no significant difference in the incidence of complications between the two groups. The degree of inflammatory cytokines changes caused by LRR was less than that of open radical surgery (P < 0.001). LRR surgery has less stress on patients with early cervical cancer than open surgery within 5 days after surgery, which has certain reference value for early cervical cancer treatment.

Cervical cancer screening abnormalities in immunosuppressed renal transplant women: case–control study in Southern Brazil

To evaluate the prevalence of cervical pre-malignancies in the cervical cytology of female renal transplant recipients (RTR) and compare to immunocompetent patients. A prospective case-control study of 165 RTR (cases) and 372 immunocompetent women (controls) was carried out from May 2015 to August 2016. The participants completed a questionnaire with demographic characteristics, habits, reproductive history, and information about the renal transplant. Cervical cytology samples were collected at their visit for cervical cancer screening. Relevant medical history was obtained from medical records and previous cervical cytology results were retrieved: from the time of kidney transplantation to the beginning of this study for RTR and all collected throughout life for controls. The mean age was similar between groups (42.6 ± 11.4 vs. 41.8.2 ± 11.1 years, p = 0.447). Considering cervical cytology collected since the kidney transplant, RTR had three times higher rates of abnormal cervical cytology test (24.8% of RTR vs. 6.3% for controls), and the abnormalities were more frequent (p  0.05). When the altered results were broken down, a higher frequency of LSIL could be seen in RTR (3.6% vs 0.0%, p = 0.008). RTR had significantly higher rates of cervical cytology abnormalities comparing to the control group and most of it was composed of LSIL.

Value of indocyanine green pelvic lymph node mapping in the surgical approach of cervical cancer

Lymph node metastasis is a significant predictive factor for disease recurrence and survival in cervical cancer patients and relevant for therapeutic strategies. We evaluated the clinical value of indocyanine green (ICG) by measuring the sensitivity and negative predictive value of sentinel lymph node mapping compared with the gold standard of complete lymphadenectomy in detecting lymph node metastases for cervical cancer. We utilized the near-infrared imaging agent ICG to detect tumor-infested lymph nodes in the pelvis analogue to a classical sentinel lymph node procedure by analyzing data from 20 patients who had undergone surgery for cervical cancer at our institution. A laparoscopic lymph node mapping procedure by means of ICG, followed by a complete pelvic lymphadenectomy with or without paraaortic lymphadenectomy was done in all patients. Histological examination identified seven patients with tumor-positive pelvic nodes, whereas mapping with ICG identified only five of these patients. Detection rate of positive nodes by ICG mapping and false negative rate was 71.4% and 28.6%, respectively; bilateral detection rate was 83.3%. One of the two false negative patients additionally suffered from deep infiltrating endometriosis. Our results indicate that ICG can identify the relevant pelvic nodes independent of tumor size, provided bilateral detection is achieved and additional, related diseases are excluded. This trial is registered within the German Clinical Trial Register (DRKS-ID: DRKS00014692).

Analysis of HPV genotype-specific concordance between EUROArray HPV and HPV 3.5 LCD-Array Kit in cervical samples of 163 patients

Human papilloma virus (HPV) as the most common viral infection of the anogenital tract is highly associated with intraepithelial neoplasia and cancer of the cervix and other anogential regions. To date, 15 high-risk (HR-) HPV and 3 probably/possibly HR-HPVs have been found to be associated with cervical cancer. Therefore, a screening especially for HR-HPV by appropriate tests is important for detection of precancerous lesions to prevent cancer. The purpose of this study was to analyze prospectively the concordance of the EUROArray HPV genotyping assay (Euroimmun; EUROArray) and the HPV 3.5 LCD-Array Kit (Chipron; LCD-Array). Liquid-based, clinician-collected cervical cytology samples (n = 163) from women undergoing cervical inspection at the dysplasia consultation in the colposcopy clinic at the Medical Center-University of Freiburg, Germany were analyzed. Genotype-specific agreement was assessed by Cohen's kappa statistic and McNemar's P value of significance between proportions. Seventeen of the HR-HPV genotypes included in both assays were detected in 42.3% and 38% of samples by EUROArray and by LCD-Array, respectively; i.e. an agreement of 92.0% and a kappa value of 0.83 could be proven between the EUROArray and the LCD-Array. In 50 of 72 samples, identical HR-HPV genotypes were analyzed (81.9%, κ = 0.47) and genotyping for HPV 16 and/or 18 was highly concordant in both tests (relative agreement 96.3%, κ = 0.88). Detection of any HR-HPV was not significantly different after comparison of EUROArray with LCD-Array. Both of the tests showed comparable results for the detection of HPV in cervical specimens and permit these assays to be suitable for routine diagnostics.

Electrochemotherapy as a symptom-oriented palliative treatment option: an exploratory single-center study in 15 patients with locally advanced or locoregionally recurrent vulvar carcinoma

Abstract Background Vulvar carcinoma (VC), a rare cancer, recurs in over a third of women, usually within 2 years. Treatment options other than repeat surgery and radiotherapy are often required in the recurrence setting. Systemic chemotherapy is an option but is generally associated with stressful side effects. In the palliative setting, electrochemotherapy (ECT) is a better-tolerated alternative, which provides local tumor control while obviating systemic side effects. Objective To descriptively analyze a case series of patients with inoperable locally advanced or locoregionally recurrent VC receiving bleomycin-based ECT. Methods Descriptive analysis of prospectively collected data from a case series. Postmenopausal women with locally advanced or locoregionally recurrent VC were eligible for inclusion. Bleomycin was administered at 15 mg/m 2 body surface as a single 1-min intravenous injection; 8 min later, electrochemical treatment using sterile disposable electrodes was performed under anesthesia for ≤ 30 min. Postoperatively, patients received pain medication to mitigate muscle soreness. Results 15 patients were included in the study. Median patient age at ECT was 81 (range, 51–100) years. Recurrences (1–5) were present in 12 patients. Surgery and radiotherapy were not justifiable options in 3 patients. In our clinical observation, ECT was well tolerated by all patients for the management of pain, itching, odor, and secretion. This allowed for time to be gained until further treatment became necessary or disease progression occurred. Conclusions In our clinical experience, bleomycin-based ECT is an oncologically efficacious and better-tolerated alternative to systemic chemotherapy or immunotherapy in patients with recurrent VC in a palliative setting with limited capacity to undergo treatment.

Comparison of different histomorphological grading systems in vulvar squamous cell carcinoma

Histopathological biomarkers of carcinomas and their prognostic relevance, such as Broder's grading system (based on the total number of undifferentiated cells) or Bryne's grading system (rating morphological features at the tumor invasive front), have been repeatedly and successfully put to test. Since most studies focus on head and neck cancers or oral carcinomas, for squamous cell carcinoma of the vulva, no standardized and agreed on pathological tumor grading system, yielding prognostic significance, could be determined so far. To determine prognostic associations of different grading systems with regard to groin lymph node metastasis, 73 cases of vulvar carcinomas (VC) were re-examined within our study and Broder's and Bryne's grading system individually performed. To sub-classify between HPV-associated or HPV-independent VC, immunohistochemical p16 stainings were performed. Statistical relationships were evaluated using Spearman correlation and logistic regression analysis, validation was achieved by employment of the likelihood ratio test (LRT) and assessment of ROC curves/AUC values. Within our cohort, Broder's grade I (40≈55%) and Bryne's grade II (48≈66%) were the most frequently assigned histological gradings. We determined a positive correlation of Bryne's grading with the extent of lymph node involvement in HPV-associated tumors and demonstrated the feasibility of Bryne's grading to predict the presence of carcinoma cells within groin lymph nodes (LRT p = 0.0066; AUC value≈0.91) in this cohort. On the other hand, our data suggest that especially HPV-independent tumors may not sufficiently be characterized by current standardly performed grading approaches. Since only Bryne's grading system correlated positively with lymph node involvement in HPV-associated squamous cell carcinoma of the vulva, we propose to include it by name next to the distinct tumor entity on the histopathological report, allowing not only the interpretation of its prognostic relevance but also future research attempts.

Uterine corpus invasion in cervical cancer: a multicenter retrospective case–control study

To determine the accuracy of uterine corpus invasion (UCI) diagnosis in patients with cervical cancer and identity risk factors for UCI and depth of invasion. Clinical data of patients with cervical cancer who underwent hysterectomy between 2004 and 2016 were retrospectively reviewed. UCI was assessed on uterine pathology. Independent risk factors for UCI and depth of invasion were identified using binary and ordinal logistic regression models, respectively. A total of 2,212 patients with cervical cancer from 11 medical institutions in China were included in this study. Of these, 497 patients had cervical cancer and UCI, and 1,715 patients had cervical cancer and no UCI, according to the original pathology reports. Retrospective review of the original pathology reports revealed a missed diagnosis of UCI in 54 (10.5%) patients and a misdiagnosis in 36 (2.1%) patients. Therefore, 515 patients with cervical cancer and UCI (160 patients with endometrial invasion, 176 patients with myometrial invasion < 50%, and 179 patients with myometrial invasion ≥ 50%), and 1697 patients with cervical cancer without UCI were included in the analysis. Older age, advanced stage, tumor size, adenocarcinoma, parametrial involvement, resection margin involvement, and lymph node metastasis were independent risk factors for UCI. These risk factors, except resection margin involvement, were independently associated with depth of UCI. UCI may be missed or misdiagnosed in patients with cervical cancer on postoperative pathological examination. Older age, advanced stage, tumor size, adenocarcinoma, parametrial involvement, resection margin involvement, and lymph node metastasis were independent risk factors for UCI and depth of UCI, with the exception of resection margin involvement.

A study of recurrence, complication and survival rates in patients with early stage vulval cancer undergoing sentinel lymph node sampling: a single-centre experience

Groin sentinel lymph node (SLN) identification and removal has become a standard of care for women with clinical early stage vulval cancer. There is evidence to support safe detection of the SLN with minimal morbidity. The purpose of this study is to report our experience of managing patients focusing on patient selection, adverse events, quality assurance of the procedure and any benefits and/or disadvantages to patients. This was a retrospective study of patients with clinical early stage vulval cancer in a cancer centre over 5 years. Notes and hospital data were reviewed including admissions to emergency departments. Statistical software was used for the statistical analysis and the Kaplan Meier survival curve was generated to present survival rates. 61 cases were analysed. A total of 156 nodes have been removed and positive nodes were identified in 14 cases. In total, 9 women (14.75%) had disease recurrence within 5 years from primary surgery. Overall, 4 patients (6.5%) developed groin recurrence. In 3 of these patients there was isolated groin recurrence (4.9%). The median length of admission was 3 days and 6 cases were managed as day cases. Since the closure of the GROINNS-2 trial we have continued the procedure of SLN identification for women with clinical early stage vulval cancer. We have shown high level of adherence to our protocol and survival and complication rates comparable to other studies on the same field. There were a few patients managed as day-case which was of benefit to the patients.

Detection of sentinel lymph node in vulvar cancer using 99mTc-labeled colloid lymphoscintigraphy, blue dye, and indocyanine-green fluorescence: a meta-analysis of studies published in 2010–2020

Sentinel lymph node (SLN) biopsy is widely accepted in the surgical staging of early vulvar cancer, although the most accurate method for its identification is not yet defined. This meta-analysis aimed to determine the technique with the highest pooled detection rate (DR) for the identification of SLN and compare the average number of SLNs detected by planar lymphoscintigraphy (PL), single-photon emission computed tomography/computed tomography (SPECT/CT), blue dye and indocyanine green (ICG) fluorescence. The meta-analysis was conducted according to the PRISMA guideline. The search string was: "sentinel" and "vulv*", with date restriction from 1st January 2010 until Dec 31st, 2020. Three investigators selected studies based on: (1) a study cohort or a subset of a minimum of 10 patients with vulvar cancer undergoing either PL, SPECT/CT, blue-dye, or ICG fluorescence for the identification of SLN; (2) the possibility to extrapolate the DR or the average number of SLNs detected by a single technique (3) no evidence of other malignancies in the patient history. A total of 30 studies were selected. In a per-patient and a per-groin analysis, the DR for SLN of PL was respectively 96.13% and 92.57%; for the blue dye was 90.44% and 66.21%; for the ICG, the DR was 91.90% and 94.80%. The pooled DR of SPECT/CT was not calculated, since only two studies were performed in this setting. At a patient-based analysis, no significant difference was documented among PL, blue dye, and ICG (p = 0.28). At a per-groin analysis, PL and ICG demonstrated a significantly higher DR compared to blue dye (p < 0.05). The average number of SLNs, on a per-patient analysis, was available only for PL and ICG with a median number of 2.61 and 1.78 lymph nodes detected, respectively, and no significant statistical difference. This meta-analysis favors the use of ICG and PL alone and in combination over blue dye for the identification of the SLN in vulvar cancer. Future studies may investigate whether the combined approach allows the highest DR of SLN in patients with vulvar cancer.

“Clock mapping” prior to excisional surgery in vulvar Paget’s disease: tailoring the surgical plan

Paget disease is a rare neoplasm of the skin that mainly involves the vulvar region. Vulvar Paget's disease (VPD) can spread beyond the apparent edges of the lesion resulting in a high risk of involved surgical margins. Our aim is to verify the efficacy of a preoperative vulvo-vaginal intensive clock mapping in the prediction of the invasiveness and the extension of VPD. All consecutive patients with primary VPD referred to our institution from July 2005 to December 2018 were subjected to a preoperative intensive biopsy mapping (clock mapping) of the vulvo-vaginal area: inside and outside the vulvar skin visible lesion, according to o'clock positions, and in the vagina. Patients with positive biopsies "only inside" or "also beyond" the visible lesion were included, respectively, in Group A and B. Surgical excision was drawn passing by the points with negative histology. Pathological findings of mapping biopsies were compared with those from radical surgery. A total of 28 women were enrolled. After clock mapping definitive histology: 17 (60.7%) and 11 (39.3%) patients were included in Group A and B. Definitive histology showed non-invasive, micro-invasive and invasive VPD, respectively, in 13 (46.4%), 11 (39.3%) and 4 (14.3%) patients, with 4 patients further upstaged. Overall, negative margins were found in 14 (50%) patients: 9 (32.1%) from Group A and 5 (17.9%) from Group B. In 23 cases (82.1%), clock mapping identified free surgical margins along the vulvo-perineal skin excision front. Preoperative clock mapping emerged as potentially useful workup tool to predict invasiveness and extension of VPD, to tailor surgical excision.

Prognostic factors for recurrence and survival in uncommon variants of vulvar cancer

To analyze the prognostic factors of recurrence and overall survival in rare histotypes of vulvar cancer. An international multicenter retrospective study including patients diagnosed with vulvar cancer was performed. One hundred centers participated in the study and 2453 vulvar cancer cases were enrolled from January 2001 until December 2005. After exclusion of squamous vulvar cancer, Paget´s disease and vulvar melanoma 112 tumors were analyzed for the present study. The mean age at diagnosis was 64.9 ± 17.2 years. 99 (88.4%) patients had a single lesion, in 25 (22.3%) cases the vulvar tumor involved the midline, and only 13 (11.5%) patients had clinically positive inguinal lymph nodes. The mean size of the lesion was 33.8 ± 33.9 mm. Regarding the surgical treatment, 2 (1.8%) patients underwent skinning vulvectomy, 63 (56.3%) local excision, 41 (36.6%) vulvectomy, 3 (2.7%) exenteration and 3 (2.7%) did not receive any surgical treatment. The mean free surgical margin was 8.2 ± 9 mm and 7 (6.2%) patients presented positive inguinal nodes. Radiotherapy was administered in 22 (19.6%) patients and it was performed postoperatively in all cases; 14 (12.5%) patients received adjuvant chemotherapy. The mean overall follow-up time was 44.1 ± 35.7 months. The risk factors associated with overall survival were chemotherapy and radiotherapy, tumor size and stromal invasion (p < 0.05). The only independent factor significantly associated with global recurrence and absence of metastasis was radiotherapy (p = 0.02 and p = 0.002, respectively). Postoperative radiotherapy seems to be the only independent factor associated with recurrence and overall survival in uncommon types of vulvar cancer.

Clinical characteristics and risk factors of invasion in extramammary Paget’s disease of the vulva

This study aimed to evaluate the risk factors of recurrence and invasive disease in patients with extramammary Paget's disease of the vulva (EPDV). We performed a retrospective analysis of patients who were initially diagnosed with EPDV in Fudan University Shanghai Cancer Center between May 2006 and March 2019. Thirty-eight patients were initially diagnosed with EPDV in our institution. Among them, 29 had intraepithelial EPDV, 8 had intraepithelial EPDV with stromal invasion, and 1 had an underlying vulvar adenocarcinoma. In total, 8 (21%) patients had 12 recurrences. Of these eight patients, four had one recurrence, while other four had two recurrences. Intraepidermal EPDV recurred nine times, while intraepidermal EPDV with invasive disease recurred thrice. The first and second recurrence intervals were 62.1 (9-146) months and 22 (15-28) months, respectively. The rate of invasive disease was 23.7% (9/38) for primary EPDV and 25% (3/12) for recurrent ones. We determined that the presence of invasive disease was associated with a history of more than 10 years (p = 0.02) and inversely correlated with positive margins (p = 0.037), However, invasive disease had no statistical relations with age (p = 0.438), recurrence (p = 0.642), and lesion diameter (p = 0.08). EPDV with a history of more than 10 years was associated with invasive disease. Close and long-term follow-up are recommended to identify those who require further treatment.

Quality of life and associated factors after surgical treatment of vulvar cancer by vulvar field resection (VFR)

Abstract Purpose To investigate patient-reported quality of life (QoL) and associated factors in vulvar cancer patients treated surgically by vulvar field resection (VFR) without adjuvant radiation. Methods We retrospectively evaluated patient-reported QoL as part of the prospective monocentric VFR trial using the 30-item European Organization for Research and Treatment of Cancer quality-of-life questionnaire (EORTC QLQ-C30) supplemented by a question assessing sexual activity. All patients had been treated by VFR and no participant had received adjuvant radiotherapy. The gynecologic cancer lymphedema questionnaire (GCLQ) was used to determine the presence of lymphedema. Structured telephone interviews were conducted to assess postoperative sequelae and long-term complications. Results Forty-three VFR patients (median age 63 years) were available for QoL assessment. Thirty-eight (88%) had received inguinal lymph-node dissection in addition to VFR. Mean global QoL (global health status) rating among all patients was 66.1 (± 25.5) on a scale from 0 to 100 with higher scores indicating better QoL. Higher GCLQ scores were significantly associated with lower global QoL scores (Spearman's rank correlation ρ =− 0.7, p &lt; 0.0001). The presence of preoperative co-morbidities and postoperative wound-healing complications were also linked to reduced QoL (p &lt; 0.01 for both). In a multivariable regression model, there was a significant interaction between preoperative co-morbidities and wound-healing complications with regard to global QoL (p &lt; 0.05). Conclusion Overall, VFR patients exhibit good quality of life postoperatively. The presence of lymphedema, wound-healing complications, and preoperative morbidities were associated with reduced QoL. Prospective longitudinal studies have to confirm our findings in the future.

Feasibility of internal inguinoperitoneal drainage after inguinofemoral lymphadenectomy in vulvar cancer

Despite the introduction of sentinel node biopsy in patients with vulvar cancer, still approximately 50% of all patients have to undergo an inguinofemoral lymphadenectomy. This is associated with a high incidence of postoperative complications, which may be influenced by inguinal drain management. The aim of this study was to investigate the feasibility of a new surgical technique regarding drain management with an inguinoperitoneal drainage. A retrospective analysis of 21 vulvar cancer patients with inguinofemoral lymphadenectomy was conducted. A silicone drain was circularly placed with the perforated end in the groin and the other end in the space of Douglas. The removal after 3 months was performed under local anesthesia. All patients were questioned during clinical follow-up regarding their personal experiences with the procedure, the occurrence of complications, and side effects using a clinical questionnaire. In 100% of the patients, the procedure was feasible. Regarding the number of groin punctures due to lymphocyst formation, 15 (71.4%) patients did not need any intervention and 3 (14.3%) patients needed 1-3 punctures. The patient satisfaction with the internal drainage was ranked as good by 17 (81.0%) patients and as moderate by 1 (4.8%) patient. In 3 (14.3%) patients, information about the number of groin punctures and the patient satisfaction were missing. Inguinoperitoneal drainage after inguinofemoral lymphadenectomy in vulvar cancer patients is feasible and safe and a patient satisfaction of 81% is promising. For definitive conclusions regarding the efficacy of this technique, further investigations and prospective multicenter trials are needed.

Risk factors associated with HPV persistence after conization in high-grade squamous intraepithelial lesion

Persistence of HPV infection in patients with high-grade squamous intraepithelial lesion (HSIL) undergoing cervical excision is considered strongly associated with the recurrence and progression of cervical dysplasia. This study aims to review potential risk factors for persistence of HPV infection in patients with HSIL, thus optimizing the postoperative monitoring program and clinical treatment. Through literature review, published data about estimated prognostic risk factors for persistence of HPV infection in patients with HSIL after conization within two decades were searched and analyzed, and their references were manually reviewed as well. Women with persistence of HPV infection after cervical excision were at an extremely high risk of disease recurrence and progression to cervical cancer. Some clinicopathological and even physiological elements involving viral, organic human body and treatment factors, such as human papillomavirus (HPV) 16, high viral load, age older than 50 years and positive surgical margin were of prognostic significance in persistent HPV infection in patients with HSIL, yet some of which still remained controversial. Monitoring prognostic factors in women with persistence of HPV infection who have underwent cervical excision for HSIL are of great significance, especially the follow-up within 2 years postoperatively, which significantly improves the clinical outcome.

Prognostic value of the number of the metastatic lymph nodes in locally early-stage cervical cancer: squamous cell carcinoma versus non-squamous cell carcinoma

To clarify the prognostic value of the number of metastatic lymph nodes (mLNs) in squamous and non-squamous histologies among women with node-positive cervical cancer. One hundred ninety-one node-positive cervical cancer patients who had undergone radical hysterectomy plus systematic pelvic and para-aortic lymphadenectomy followed by concurrent radiochemotherapy were retrospectively reviewed. The prognostic value of the number of mLNs was investigated in squamous cell carcinoma (SCC) v (n = 148) and non-SCC (n = 43) histologies separately with univariate log-rank test and multivariate Cox regression analyses. In SCC cohort, mLNs > 2 was significantly associated with decreased 5-year disease-free survival (DFS) [hazard ratio (HR) = 2.06; 95% confidence interval (CI) 1.03-4.09; p = 0.03) and overall survival (OS) (HR = 2.35, 95% CI 1.11-4.99; p = 0.02). However mLNs > 2 had no significant impact on 5-year DFS and 5-year OS rates in non-SCC cohort (p = 0.94 and p = 0.94, respectively). We stratified the entire study population as SCC with mLNs ≤ 2, SCC with mLNs > 2, and non-SCC groups. Thereafter, we compared survival outcomes. The non-SCC group had worse 5-year OS (46.8% vs. 85.3%, respectively; p  2 had similar 5-year OS (46.8% vs. 65.5%, respectively; p = 0.16) and 5-year DFS rates (31.6% vs. 57.5%, respectively; p = 0.06). Node-positive cervical cancer patients who have non-SCC histology as well as those who have SCC histology with mLNs > 2 seem to have worse survival outcomes when compared to women who have SCC histology with mLNs ≤ 2.

Comparison between laparoscopic and abdominal radical hysterectomy for low-risk cervical cancer: a multicentre retrospective study

To compare oncological outcomes of laparoscopic radical hysterectomy (LRH) and abdominal radical hysterectomy (ARH) for low-risk cervical cancer. We retrospectively compared the 3-year overall survival (OS) and 3-year disease-free survival (DFS) of 1269 low-risk cervical cancer patients with FIGO 2009 stage IA2, IB1 and IIA1 with a tumour size < 2 cm, no lymphovascular space invasion (LVSI), superficial stromal invasion and no lymph node involvement on imaging, and who received LRH (n = 672) and ARH (n = 597) between 2009 and 2018 at 47 hospitals. In the total study population, LRH and ARH showed similar 3-year OS (98.6% vs. 98.9%, P = 0.850) and DFS rates (95.7% vs. 96.4%, P = 0.285). LRH was not associated with worse 3-year OS (HR 0.897, 95% CI 0.287-2.808, P = 0.852) or DFS (HR 0.692, 95% CI 0.379-1.263, P = 0.230) as determined by multivariable analysis. After propensity score matching in 1269 patients, LRH (n = 551) and ARH (n = 551) still showed similar 3-year OS (98.4% vs. 98.8%, P = 0.704) and DFS rates (95.5% vs. 96.3%, P = 0.249). LRH was still not associated with worse 3-year OS (HR 0.816, 95% CI 0.262-2.541, P = 0.725) or DFS (HR 0.694, 95% CI 0.371-1.296, P = 0.251). Among patients with low-risk cervical cancers < 2 cm, no LVSI, superficial stromal invasion, and no lymph node involvement on imaging, no significant differences were observed in 3-year OS or DFS rates between LRH and ARH.

Laser vaporization of the cervix is associated with an increased risk of preterm birth and rapid labor progression in subsequent pregnancies

Laser vaporization of the cervix is an established method of treating cervical intra-epithelial neoplasia, but its effect on subsequent pregnancies remains controversial. The aim of this study was to investigate pregnancy outcomes after laser vaporization. We conducted a retrospective study involving women who delivered live singletons between 2012 and 2019 in a tertiary hospital. The risks of adverse pregnancy outcomes after laser vaporization of the cervix were assessed using a multivariate regression model. The primary outcome was the adjusted odds ratio for preterm births. We also evaluated the course of labor progression, duration of labor, risk of emergency cesarean deliveries, and the risk of cervical laceration as secondary outcomes. In total, 3359 women were analyzed in this study. The risk of preterm birth was significantly higher in pregnancies after laser vaporization of the cervix (adjusted odds ratio [AOR] 1.84, 95% confidence interval [95% CI] 1.06-3.20; p = 0.030). The duration of the first stage of labor was significantly shorter in the post-treatment group (median 255 min vs. 355 min; p = 0.0049). We did not observe significant differences in the duration of the second stage of labor (median 21 min vs 20 min; p = 0.507) or the rates of other obstetric events, including emergency cesarean deliveries (AOR 0.736; 95% CI 0.36-1.50; p = 0.400) and cervical laceration (AOR 0.717; 95% CI 0.22-2.35; p = 0.582). Laser vaporization of the cervix is associated with an increased risk of preterm births and a shorter duration of the first stage of labor in subsequent pregnancies. Careful consideration is necessary when selecting a method of treatment for the uterine cervix of patients wishing future pregnancies.

Analysis of the agreement between colposcopic impression and histopathological diagnosis of cervical biopsy in a single tertiary center of Chengdu

The aim of this retrospective study was to analyze the agreement between colposcopic impression and histopathological diagnosis of cervical biopsy. The medical records of patients underwent a colposcopy-guided cervical biopsy at Chengdu Women's and Children's Central Hospital between January 2017 and January 2019 were collected, including age, menopausal status, cervical cytology and human papillomavirus (HPV) test results, type of transformation zone, colposcopic diagnosis and histopathological outcomes of cervical biopsy. Colposcopy was carried out using 2011 colposcopic terminology of International Federation for Cervical Pathology and Colposcopy (IFCPC). Related variables were analyzed. A total of 495 patients were collected in this study. The perfect agreement between colposcopic impression and histopathological diagnosis was 46.9%, and the strength of agreement with kappa value was 0.283 (P < 0.001), and the agreement within 1 grade was 93.5%. Positive predictive value (PPV), negative predictive value (NPV), sensitivity, specificity, false-positive rate and false-negative rate of detecting HSIL or more (HSIL +) were 93.1%, 57.8%, 80.9%, 93.9%, 6.1% and 45.3%, respectively. Colposcopic diagnosis more often underestimated (43.2%) [especially in HSIL (59.3%) and carcinoma (70.7%) patients] than overestimated (9.9%) in cervical lesions. The results of cytology, HPV status, patients' age and different experiences of practitioners were the factors for under-diagnosis of HSIL + by colposcopy. Colposcopy is an excellent tool to estimate cervical high-grade lesion but is imprecise. Many factors can bias the diagnosis of colposcopy, especially the known results of cervical cytology and HPV. Precise diagnosis of cervical lesion should rely on the colposcopy-directed biopsy.

Evaluation of the sexual quality of life and sexual function of cervical cancer survivors after cancer treatment: a retrospective trial

The purpose of this study was to explore the factors influencing the sexual quality of life of patients with cervical cancer who underwent radical hysterectomy. This multicenter retrospective cohort study was conducted from June 2013 to June 2018 at nine hospitals in China. In total, 204 women diagnosed with stage IA to stage IIB cervical cancer who underwent radical hysterectomy completed the questionnaire. Sexual function was measured with the Pelvic Organ Prolapse/Urinary Incontinence Sexual Questionnaire (PISQ). All analyses were performed with R version 3.4.3 statistical software packages. A two-sided significance level of 0.05 was used to evaluate the statistical significance. The mean sexual quality of life score was 37.21 ± 17.28, where a higher PISQ score indicates a better sexual quality of life, and we identified the factors associated with sexual dysfunction. The average follow-up time was 29.0 ± 16.0 months. In addition to radical hysterectomy, 182 (89.2%) patients underwent ovarian suspension, 93 (45.6%) underwent chemotherapy, and 74 (36.3%) underwent concurrent radiotherapy. The univariate analysis confirmed that age represents a protective factor for sexual function (odds ratio (OR) 6.0, 95% confidence interval (CI) 1.1-10.8, p = 0.017). The patients who underwent ovarian suspension were more likely to experience a good sexual quality of life (OR - 7.2, 95% CI [- 14.8, - 0.4], p = 0.035) compared to those who did not undergo ovarian suspension. A significant negative association was observed between radiotherapy and the behavioral-emotive, physical and partner-related domains of the PISQ (behavioral-emotive, OR - 1.5, 95% CI [- 2.6, - 0.4], p = 0.011; physical, OR - 0.9, 95% CI [- 1.5, - 0.3], p = 0.006; partner-related, OR - 0.7, 95% CI [- 1.3, 0.0], p = 0.043). Chemotherapy and radiotherapy were common risk factors for sexual dysfunction, and radiotherapy exerted a stronger effect than chemotherapy. This study shows that the sexual function of cervical cancer patients tends to be related to age, radiotherapy, and chemotherapy. However, across these factors, patients with preserved ovaries tend to return to a satisfactory sexual quality of life after recovering from surgery.

Detection of DKK-1 gene methylation in exfoliated cells of cervical squamous cell carcinoma and its relationship with high risk HPV infection

To detect the methylation of Dickkopf-associated protein 1 (DKK-1) gene promoter in cervical exfoliated cells and to study its clinical significance in cervical squamous cell carcinoma (CSCC) and its relationship with high-risk HPV infection. Methylation-specific PCR (MSP) was utilized to detect the methylation of DKK-1 gene promoter in cervical exfoliated cells from 40 patients with CSCC and 40 patients with chronic cervicitis in the Affiliated Hospital of Inner Mongolia Medical University. The methylation rate of DKK-1 gene promoter in different clinicopathological factors and its relationship with high-risk HPV infection was compared, and different detection methods were compared. The degree of methylation of DKK-1 gene promoter in CSCC group was significantly higher than that in cervicitis group (P  0.05). The one-year survival rate of CSCC patients with high-risk HPV positive and DKK-1 gene promoter methylation is relatively low, only 74.1%. The sensitivity, specificity and accuracy of DKK-1 gene methylation combined with high-risk HPV detection were 96.7%, 78.0% and 85.0%, respectively. Methylation of DKK-1 gene promoter in cervical exfoliated cells of patients with CSCC is related to high-risk HPV infection and different clinicopathological factors, but the degree of methylation of DKK-1 gene is not related to the type of high-risk HPV infection. It may become an indicator different from HPV typing detection, which may play a shunt role in suggesting whether further invasive cervical examination is needed and reduce cervical invasive examination and overtreatment. It may be related to the survival rate of patients, which can be used to estimate the development and prognosis of CSCC and may play a good role in early warning in follow-up monitoring of CSCC after treatment. DKK1 gene methylation combined with HPV detection can improve the sensitivity, specificity and accuracy of diagnosis, which may improve the detection rate of early CSCC and make up for the deficiency of HPV and TCT detection. That may become a non-invasive screening method for CSCC.

Minimal-invasive or open approach for surgery of early cervical cancer: the treatment center matters

The aim of the study was to compare recurrence-free survival (RFS) and overall survival (OS) of patients with early stage cervical cancer in dependence of surgical approach and treatment center. A population-based cohort study including women with early stage IA1-IIB2 cervical cancer treated by radical hysterectomy between January 2010 and December 2015 was performed. The median follow-up time was 5.6 years. After exclusions, 413 patients were eligible for analysis: 111 (26.9%) underwent minimal-invasive surgery (MIS) and 302 (73.1%) open surgery. Both treatment groups were well balanced regarding the clinical and pathological characteristics. The mean age of the patients was 51.0 years. MIS was associated with improved RFS and OS compared with the open surgery. The 5-year RFS rates were 89.2% in the MIS group and 73.4% in the open surgery group (p = 0.004). The 5-year OS rates were 93.7% in the MIS group and 81.8% in the open surgery group (p = 0.016). After adjustment for other prognostic covariates, the MIS was further associated with improved RFS (HR = 0.45, 95% CI 0.24-0.86; p = 0.015) but not with OS. Nevertheless, after adjustment for treatment center, the surgical approach was not associated with significant difference in RFS (HR = 0.61, 95% CI 0.31-1.19; p = 0.143). Overall survival of patients treated in university cancer centers was significantly increased compared to patients treated in non-university cancer centers. The treatment center remains a strong prognostic factor regarding RFS (HR = 0.49, 95% CI 0.28-0.83; p = 0.009) and OS (HR = 0.50, 95% CI 0.26-0.94; p = 0.031). The treatment center but not the surgical approach was associated with the survival of patients treated with radical hysterectomy for early stage cervical cancer.

Survival outcomes of neoadjuvant chemotherapy-related strategies compared with concurrent chemoradiotherapy for locally advanced cervical cancer: a meta-analysis of randomized controlled trials

The survival benefits of neoadjuvant chemotherapy (NAC) compared with those of concurrent chemoradiotherapy (CRT) for locally advanced cervical cancer (LACC) patients remain uncertain. Meta-analysis was used to compare NAC and CRT. A systematic search was performed up to 9 September 2020. Survival outcomes were analyzed based on event frequency or hazard ratios (HRs). Multilevel mixed-effects logistic regression was applied to analyze the effect of regimen variables on survival outcomes. Analysis based on Cox regression showed that CRT was better than NAC + radical hysterectomy (RT) (HR 1.25; 95% confidence interval (CI)) 1.02-1.54; p = 0.034) in terms of overall survival (OS). According to multilevel mixed-effects model analysis comparing NAC + RT and CRT, LACC patients who used cisplatin instead of carboplatin had a better Progression-free survival (PFS) (odds ratio (OR) 1.54; 95% CI 1.08-2.20; p = 0.016). When NAC + CRT and CRT were compared, gemcitabine administration was associated with a decrease in PFS (OR 0.47; 95% CI 0.22-0.99; p = 0.047). Increased doses of cisplatin and paclitaxel were associated with survival improvement. Based on traditional meta-analysis, CRT was better than NAC + RT in terms of OS. Carboplatin instead of cisplatin as part of the NAC + RT strategy or gemcitabine use in NAC + CRT may not be a good choice. An increased total dosage of paclitaxel and/or cisplatin as part of NAC + CRT and CRT strategies may improve the survival outcome of LACC patients.

Assessment of high-risk human papillomavirus infections and associated cervical dysplasia in HIV-positive pregnant women in Germany: a prospective cross-sectional two-centre study

Invasive cervical cancer (ICC) is associated in nearly 100% with persistent high-risk Human Papillomavirus (HR-HPV) infection. ICC is still one of the leading causes for cancer mortality in women worldwide. The immunosuppressive influence of Human Immunodeficiency Virus (HIV) and the immunocompromised period of pregnancy due to tolerance induction against the hemiallogeneic fetus, are generally risk factors for acquisition and persistence of HR-HPV infections and their progression to precancerous lesions and HPV-associated carcinoma. Overall, 81 pregnant women living with HIV (WLWH) were included. A medical history questionnaire was used to record clinical and HIV data. Participants received cervicovaginal cytological smear, colposcopy and HPV testing. HPV test was performed using BSGP5+/6+ PCR with Luminex read-out. The HR-HPV genotypes 16, 18, 31, 33, 45, 52, 58 were additionally grouped together as high-high-risk HPV (HHR-HPV) for the purpose of risk-adapted analysis. HR-HPV prevalence was 45.7%. Multiple HPV infections were detected in 27.2% of participants, of whom all had at least one HR-HPV genotype included. HR-HPV16 and HR-HPV52 were the most prevalent genotypes and found when high squamous intraepithelial lesion (HSIL) was detected by cytology. HIV viral load of ≥ 50 copies/ml was associated with higher prevalence of HR-HPV infections. Whereas, CD4 T cells < 350/µl showed association with occurrence of multiple HPV infections. Time since HIV diagnosis seemed to impact HPV prevalence. Pregnant WLWH require particularly attentive and extended HPV-, colposcopical- and cytological screening, whereby clinical and HIV-related risk factors should be taken into account.

Incorporating HPV 33 and cytology into HPV 16/18 screening may be feasible. A cross-sectional study

The distribution of human papillomavirus (HPV) varies geographically, and each country is making its screening and vaccination program. This study questioned the need for colposcopy for HPV types other than HPV 16 and 18, and the need for cytology incorporated into HPV testing. 1043 consecutive patients referred for colposcopy are included in this retrospective study. Logistic regression analysis, ANOVA, and Pearson's correlation were used for statistical analysis. The value of p < 0.05 was considered statistically significant. HPV 16 was the most common HPV type referred, followed by HPV 18, 52, 51, and 31, respectively. HPV 16 tends to be positive in younger patients than other HPV types (p < 0.05). Only HPV 16 (OR: 1.41, 1.06-1.88 95% CI) and HPV 33 (OR: 2.23; 1.06-4.64 95% CI) (p < 0.05) had significant prediction for CIN 2 + lesions. In patients with only a cytological abnormality, cytological abnormality with single other high-risk (hr) HPV (without HPV 16 or 18) or double other hrHPV positivity but without HPV 16 and 18 infections, we detected 159 (19%) CIN 2 + lesions. HPV 33 may be implemented in hrHPV screening protocols for direct colposcopy referral as well as HPV 16 and HPV 18 in specific regions. If we had opted for HPV-based screening only for HPV 16 and 18 without cytology, 19% of all CIN 2 + lesions would have been missed. HPV-based screening only with HPV 16 and 18 may not be feasible. Nonavalent vaccines should be considered for the vaccination of specific populations.

Machine learning applied to MRI evaluation for the detection of lymph node metastasis in patients with locally advanced cervical cancer treated with neoadjuvant chemotherapy

Concurrent cisplatin-based chemotherapy and radiotherapy (CCRT) plus brachytherapy is the standard treatment for locally advanced cervical cancer (LACC). Platinum-based neoadjuvant chemotherapy (NACT) followed by radical hysterectomy is an alternative for patients with stage IB2-IIB disease. Therefore, the correct pre-treatment staging is essential to the proper management of this disease. Pelvic magnetic resonance imaging (MRI) is the gold standard examination but studies about MRI accuracy in the detection of lymph node metastasis (LNM) in LACC patients show conflicting data. Machine learning (ML) is emerging as a promising tool for unraveling complex non-linear relationships between patient attributes that cannot be solved by traditional statistical methods. Here we investigated whether ML might improve the accuracy of MRI in the detection of LNM in LACC patients. We analyzed retrospectively LACC patients who underwent NACT and radical hysterectomy from 2015 to 2020. Demographic, clinical and MRI characteristics before and after NACT were collected, as well as information about post-surgery histopathology. Random features elimination wrapper was used to determine an attribute core set. A ML algorithm, namely Extreme Gradient Boosting (XGBoost) was trained and validated with tenfold cross-validation. The performances of the algorithm were assessed. Our analysis included n.92 patients. FIGO stage was IB2 in n.4/92 (4.3%), IB3 in n.42/92 (45%), IIA1 in n.1/92 (1.1%), IIA2 in n.16/92 (17.4%) and IIB in n.29/92 (31.5%). Despite detected neither at pre-treatment and post-treatment MRI in any patients, LNM occurred in n.16/92 (17%) patients. The attribute core set used to train ML algorithms included grading, histotypes, age, parity, largest diameter of lesion at either pre- and post-treatment MRI, presence/absence of fornix infiltration at pre-treatment MRI and FIGO stage. XGBoost showed a good performance (accuracy 89%, precision 83%, recall 78%, AUROC 0.79). We developed an accurate model to predict LNM in LACC patients in NACT, based on a ML algorithm requiring few easy-to-collect attributes.

Metastatic extent-specific prognosis of women with stage IVB cervical cancer: multiple versus single distant organ involvement

Despite the heterogeneity of anatomical sites that metastases may affect, within the current cancer staging schematic, stage IVB encompasses all distant metastasis. This study examined survival outcomes based on the extent of distant organ metastasis in stage IVB cervical cancer. This retrospective cohort study utilized the National Cancer Institute's Surveillance, Epidemiology, and End Result Program from 2010 to 2018. The study population included 1772 women with stage IVB cervical cancer who had tumor metastasis to one or more of the following four organs: bone, brain, liver, or lung. Overall survival was assessed based on the metastatic extent in multivariable analysis. The most common metastatic site was lung (68.3%) followed by bone (35.2%), liver (30.0%), and brain (1.2%). Multiple organ metastases were seen in 26.5% of study population, with lung / liver metastases being the most frequent combination pattern (9.6%) followed by lung / bone (9.4%), and lung / bone / liver (6.4%). A total of 1442 (81.4%) deaths occurred during the follow-up. The cohort-level median overall survival was 7 months, ranging from 3 months in all four organ metastases to 11 months in bone metastasis alone when stratified (absolute difference 8 months, P < 0.001). Multiple organ metastases were independently associated with nearly 50% increased all-cause mortality risk compared to single organ metastasis (adjusted-hazard ratio 1.51, 95% CI 1.34-1.70). Survival outcomes in those with stage IVB cervical cancer with distant organ involvement can vary based on the extent of metastasis. Incorporation of single versus multiple distant organ metastasis into the cancer staging schema may be valuable (IVB1 versus IVB2).

p16/Ki-67 dual stain, PAP cytology and HR-HPV test results prior to and 6 months after a LLETZ procedure: a prospective observational cohort study

To investigate the effect of a LLETZ procedure on p16/Ki-67 dual stain, PAP cytology and HR-HPV test results on cervical cytology samples obtained prior to and 6 months after the procedure. Secondary aims are to assess dependency between test results at the time of follow-up and explore dual stain positivity rates according to known risk factors for persistence/recurrence of cervical intra-epithelial neoplasia (CIN). Prospective observational cohort study conducted in the Department of Gynaecology at the University Hospitals of Leuven, Belgium. All patients referred for a LLETZ procedure were invited to participate. A cervical cytology sample was obtained just prior to and 6 months after the procedure. Every sample was used for PAP staining (cytology), p16/Ki-67 dual staining (dual stain test, DST) and HR-HPV genotyping. Test results were compared between both timepoints using the McNemar test. Dependency was assessed cross-sectionally at the time of follow-up using a chi-squared test. From the 110 participants originally included, 83 attended follow-up (75.5%). Mean duration of follow-up was 187.91 days (SD 21.47) and mean age was 41.4 years (SD 11.08). DST positivity rates were 70.9 and 30.1% prior to and 6 months after the procedure (p < 0.001). HR-HPV testing (positive or negative) and abnormal PAP cytology (evaluated at an ASCUS or worse threshold) showed a similar significant reduction in positivity rates (84.5 vs 42.2% and 72.7 vs 28.9%, respectively, p < 0.001). Results of all three assays showed high dependency at the time of follow-up (DST and PAP, PAP and HR-HPV test, DST and HR-HPV test-p values < 0.001). The highest proportion of positive DST results was seen in patients carrying HPV16 (84.6%), followed by any HR-HPV type (60%), those treated for CIN2 + (27.3%) and those with positive margins on the cone specimen (26.7%). A LLETZ procedure results in a significant decrease in abnormal DST, PAP cytology and HR-HPV test results in this diverse cohort of patients. The highest proportion of abnormal DST results was seen in patients carrying HR-HPV at the time of follow-up, especially HPV 16.

Prevalence and genotype distribution of human papillomavirus infection among female outpatients in Northeast China: a population-based survey of 110,927 women

Human papillomavirus (HPV) infection, especially high-risk HPV, is a major etiological factor for cervical cancer. This study aimed to investigate the distribution of human papillomavirus infection among female outpatients in Northeast China. A total of 110,927 women aged between 18 and 80 years from Shengjing Hospital of China Medical University, tested with the HPV Geno-Array Test Kit (HybriBio), were enrolled in this study. The overall prevalence of HPV infection in the study population was 16.95% (18,802/110,927). A total of 21 HPV genotypes were identified and the six most prevalent ones were HPV16 (5.78%), HPV58 (2.62%), HPV52 (1.91%), HPV33 (1.55%), HPV53 (1.45%), and HPV18 (1.16%). The prevalence of single HPV was 83.58% (15,714/18802) and that of multiple HPV was 16.42% (3088/18802). HPV16, HPV58, and HPV52 were the most common types of HR-HPV infections, while CP8304, HPV11, and HPV6 were the most common types of LR-HPV infections. Among the multiple infection groups, HPV16 was the most common type of co-infection. Furthermore, the prevalence of HPV infections varied among different age groups. Age-specific prevalence of HPV exhibited two peaks in the youngest age group and in the group aged 50-60 years. HPV16, 58, 52, 33, 53, and 18 were the most common types in the general female population. The prevalence of HPV infection varied among different age groups. This study provides guidance for future HPV-based cervical cancer screening tests and prophylactic HPV vaccinations in China.

Stromal or intraepithelial tumor-infiltrating lymphocytes: which one has more prognostic significance in cervical cancer?

To investigate the effect of tumor-infiltrating lymphocytes (TILs) and tumor associated macrophages (TAMs) on treatment results in patients with cervical squamous cell carcinoma who underwent definitive or adjuvant radiotherapy (RT) or chemoradiotherapy (CRT). Pathological specimens were evaluated from 96 cervical cancer patients who were treated with definitive or adjuvant RT/CRT between April 2001 and January 2020. The percentage of intraepithelial TILs (iTILs) and stromal TILs (sTILs) were calculated, and immunohistochemistry was used for identifying lymphocyte lineage with CD4, CD8, and CD20 antibodies and macrophages with CD68 antibody. Prognostic values of TILs/TAMs on oncological outcomes were evaluated. Thirty patients had early-stage disease and 66 patients had advanced-stage disease. Sixty-three and 33 patients received adjuvant RT and definitive CRT, respectively. Low number of sCD20 positive cells was associated with large tumor size and parametrial invasion. In multivariate analysis, low percentage of sTILs and advanced-stage disease were independent poor prognostic factors for overall survival, disease-free survival (DFS), and distant metastasis-free survival; low number of sCD4 positive cells was also an independent poor prognostic factor for DFS. Low percentage of sTILs and low number of sCD8 positive cells was correlated with high rates of distant metastasis (p = 0.038 and p = 0.025, respectively). sTILs have superior predictive value than iTILs in terms of prognosis. Stromal compartment should be investigated as a routine practice in TIL studies in cervical cancer. Intensifying the treatment in cervical cancer patients with low number of sTILs should be studied in further investigations.

Comprehensive analysis of novel prognosis-related proteomic signature effectively improve risk stratification and precision treatment for patients with cervical cancer

Cervical cancer (CC) is one of the most common types of malignant female cancer, and its incidence and mortality are not optimistic. Protein panels can be a powerful prognostic factor for many types of cancer. The purpose of our study was to investigate a proteomic panel to predict the survival of patients with common CC. The protein expression and clinicopathological data of CC were downloaded from The Cancer Proteome Atlas and The Cancer Genome Atlas database, respectively. We selected the prognosis-related proteins (PRPs) by univariate Cox regression analysis and found that the results of functional enrichment analysis were mainly related to apoptosis. We used Kaplan-Meier analysis and multivariable Cox regression analysis further to screen PRPs to establish a prognostic model, including BCL2, SMAD3, and 4EBP1-pT70. The signature was verified to be independent predictors of OS by Cox regression analysis and the area under curves. Nomogram and subgroup classification were established based on the signature to verify its clinical application. Furthermore, we looked for the co-expressed proteins of three-protein panel as potential prognostic proteins. A proteomic signature independently predicted OS of CC patients, and the predictive ability was better than the clinicopathological characteristics. This signature can help improve prediction for clinical outcome and provides new targets for CC treatment.

Invasive stratified mucin-producing carcinoma (ISMC) of uterine cervix: description of pathological findings and prognosis factors in a series of 15 Chinese patients

Invasive stratified mucin-producing carcinoma (ISMC), an invasive form of stratified mucin-producing intraepithelial lesion (SMILE), is a newly named human papillomavirus (HPV) associated mucous adenocarcinoma of cervix. We aim to provide more clinical and pathological data for this uncommon disease. Fifteen cases diagnosed as ISMC in our hospital were included, and their clinical and pathological data were retrospectively analyzed. The patients' median age was 43 years (range, 30-54 years). The most prevalent symptom was abnormal vaginal bleeding. HPV test indicated high-risk HPV in all of our 15 cases. In addition, we observed several other architectural patterns of ISMC, including nest, gland-forming or lumen-forming, papillary with extravasated pools of mucin and solid. Immunohistochemically, all of our ISMC cases showed block-like expression of P16 and diffuse positive expression of CK8 and CK18, while P63, P40 and CK5/6 were spotted positive, or completely negative. Most importantly, ISMC has a relatively high lymph node metastasis rate of 33%. ISMC is a special type of HPV-associated adenocarcinoma, displaying a wide morphologic spectrum combined with a unique immunohistochemical profile. Clinically, ISMC may have a higher rate of lymph node metastasis, which suggests more attention to postoperative follow-up.

Oncologic outcomes of patients with FIGO 2014 stage IB-IIA cervical adenocarcinoma who underwent radical surgery

To identify prognostic factors of early-stage cervical adenocarcinoma in patients with FIGO IB-IIA, who were treated with radical surgery. Clinical data of 64 patients with stage IB-IIA cervical adenocarcinoma who underwent radical hysterectomy and lymphadenectomy with or without adjuvant therapy between 1993 and 2019 were retrospectively reviewed. The clinicopathologic factors that affect the oncological outcomes were evaluated. The Kaplan-Meier method was used for the assessment of survival outcomes. Survival curves were compared using the log-rank test. The 5-year recurrence-free survival and 5-year disease-specific survivals were 83% and 98%, respectively. Tumor size, stage of disease and uterine spread were significantly related prognostic factors for shorter recurrence-free survival. During the follow-up, nine (14.1%) patients recurred. Five of them were extrapelvic recurrence. No correlation was identified between histopathologic subtype and extrapelvic recurrence (p = 0.265). There was no difference between adjuvant only radiotherapy and concurrent chemoradiotherapy on recurrence-free survival in a univariate analysis adjusting for prognostic factors. It is important to determine the prognostic factors that predict disease outcome in surgically treated cervical adenocarcinoma for tailored adjuvant treatment. Tumor size, stage and uterine spread are determinant factors for recurrence. Risk stratifications, including uterine spread may especially be useful for patients with AC.

Meta-analysis of downregulated E-cadherin as a diagnostic biomarker for cervical cancer

Downregulation of E-cadherin function or expression has been implicated in the progression of cervical cancer. This meta-analysis of updated publications was performed to assess the association of expression alteration of E-cadherin with disease severity and then to determine the diagnostic accuracy of E-cadherin in discriminating cervical lesions including cervical intraepithelial neoplasia (CIN) grade 1 (CIN1), CIN grade 2 (CIN2), CIN grade 3 (CIN3), and cervical cancer. The articles published from inception to January 2021 were searched in PubMed, EBSCO, CNKI, and WanFang Database and then evaluated according to the criteria of meta-analysis. The eligible studies were retrieved and further analyzed. A bivariate mixed effects binary regression model was applied to determine pooled effect estimates. 16 studies with 2436 subjects from 7 countries were eligible for this meta-analysis. When compared with CIN1 control, the pooled odds ratios (ORs) with 95% confidence interval (CI) for the association of E-cadherin positivity with CIN2, CIN3, and cervical cancer were 0.34 (95% CI 0.23-0.51), 0.23 (95% CI 0.10-0.54), and 0.10 (95% CI 0.07-0.14), respectively. The pooled sensitivity and specificity for CIN3 or worse were 0.60 (95% CI 0.48-0.70) and 0.82 (95% CI 0.73-0.88) respectively, with the AUC of 0.78 (95% CI 0.74-0.82). Similar performance was found in CIN2 or worse. These findings demonstrated that the loss of E-cadherin protein was associated with worsened cervical lesions. E-cadherin might serve as a promising diagnostic biomarker to facilitate the discrimination of precancerous and cancerous lesions.

Does radical trachelectomy (RT) during pregnancy have higher obstetrical and oncological risks than RT before pregnancy?

Radical trachelectomy (RT) with pelvic lymphadenectomy has become a new treatment option for young patients with uterine cervical cancer stages 1A2-1B1 who desire the preservation of their fertility. However, the application of RT for pregnant patients is still controversial. We comparatively studied both obstetrical and oncological outcomes of pregnant patients who underwent vaginal RT during pregnancy and those who underwent vaginal RT before pregnancy. Both obstetrical and oncological results of eight patients who underwent vaginal RT with pelvic lymphadenectomy during pregnancy in our institute between 2010 and 2020 (Group A), and ten pregnant patients who underwent vaginal RT with pelvic lymphadenectomy before pregnancy during the same period (Group B) were reviewed based on their medical charts. There were neither significant differences in blood loss, surgical time, or surgical completeness between Group A and Group B, nor were there significant differences in obstetrical outcomes between the two groups. However, two of the eight patients in Group A had recurrence of the cancer. None of the patients in Group B has shown any signs of recurrence thus far. Vaginal RT during pregnancy does not affect the obstetrical prognoses of patients with early invasive uterine cervical cancer, and it might be a tolerable treatment modality for them. However, oncologically, it should be performed carefully as there is a risk of recurrence.

The value of the endocervical margin status in LEEP: analysis of 610 cases

To describe the results of 610 patients who underwent LEEP and evaluate factors related to a negative margin. A retrospective study of patients treated by LEEP at a colposcopy referral service in Campinas, Brazil, 2017-2019. Patients were referred to treat high-grade squamous intraepithelial lesion or adenocarcinoma in situ suspected by cytology and colposcopy (screen-and-treat) or by biopsy. Descriptive analysis was performed by frequencies as a function of the status of the margins (negative or positive). Factors associated with margin status were assessed by regression. The endocervical, ectocervical or both margins were negative in 82.4%, 75.7% and 65.9%, respectively. Age, sexual debut, parity, menopause status, smoking and hormonal contraception showed no difference in the proportion of negative margins. Both margins were negative in 66.1% of patients with transformation zone type(TZ) 1, 73.1% of TZ 2, and 54.7% of TZ 3 (p = 0.015). The endocervical negative margin was obtained in 78.0% of patients submitted to excision I (loop 10 mm) and 82.5% to excision II (loop 15 mm) (p = 0.016). Having the sexual debut at 18 years or older or being submitted to an excision type II doubled the chance of negative endocervical margin (1.98;1.04-3.77 and 1.95; 1.18-3.21, respectively). The proportion of negative endocervical margin was 78% in excision I and 86% in excision II. Sexual onset and excision type II increased the chance of obtaining a negative endocervical margin.

The detection of cervical neoplasia via optical ımaging: a pilot clinical study

The present study aims to develop a new high-resolution imaging system for the early diagnosis of cervical neoplasia based on increased vessel density of the cervical tissue. An optical device was developed to obtain high contrast and resolution images of vascular structures of the cervix in the present study. The device utilizes a telecentric lens to capture cervix images under light illumination with a wavelength of 550 nm emitted from LEDs. Images were obtained using the telecentric lens with or without acetic acid application to the cervix. Image processing algorithms were used to contrast and extract the skeleton of the vascular structures on the cervix. In the evaluation of the vascular density, the cervical images were divided into 12 o'clock positions, and the fractal dimension of the vascularity was calculated for each dial area between the o'clock positions. The region with the largest fractal dimension was accepted as the region with the highest probability of lesion. The range of vessel sizes was split into small classes of "bins" for each dial area with the highest fractal dimension. To validate the system's success in differentiating between normal and HSIL lesions, forty five patients who underwent colposcopy and biopsy were included in a pilot study. The system correctly classified four HSIL cases out of five and failed to detect one HSIL case, achieving an accuracy rate of 97.8% with an 80% sensitivity and 100% specificity. The developed high-resolution optical imaging system may potentially be used in detecting cervical neoplasia just before the biopsy and reduce the number of false-positive cases.

A dose–response meta-analysis of the relationship between number of pregnancies and risk of gynecological cancers

Despite several investigations, the association between the number of pregnancies and gynecological cancers remains inconclusive. To address this issue, we conducted a dose-response meta-analysis of observational studies. We searched PubMed, Web of Science, and Scopus databases up to Jun 8, 2023, to identify observational studies that examined the association between the number of pregnancies and gynecologic cancers. To assess the heterogeneity across studies, we used the χ Out of the 87,255 studies initially identified, a total of 101 studies involving 8,230,754 participants were included in the final meta-analysis. Our analysis revealed a positive trend between the number of pregnancies and cervical cancer; however, this association was not found to be statistically significant except for fifth pregnancy. Conversely, our findings showed a significant decreasing trend between the number of pregnancies and the risk of endometrial and ovarian cancers. There was insufficient evidence to establish a relationship between the number of pregnancies and the risk of vaginal, vulvar, and fallopian tube cancers. Our study found a positive trend between the number of pregnancies and cervical cancer and a significant decreasing trend between the number of pregnancies and endometrial and ovarian cancers. These findings may have implications for counseling women about their reproductive health and the potential risks and benefits of pregnancy.

Effect of adhesions on laparoscopically-assisted vaginal hysterectomy outcome: a 10-year retrospective, comparative study of 1683 consecutive cases

Abstract Introduction Hysterectomy is a frequently employed treatment modality in gynaecological diseases. In the context of various approaches to vaginal hysterectomy, laparoscopically-assisted vaginal hysterectomy (LAVH) could eventually improve the safety in cases where patients without genital prolapse present with preoperative peritoneal adhesions. The present analysis examined intraoperative and immediate postoperative adhesions-related outcomes. Methods Monocentric, comparative, retrospective study of a single cohort of women without genital prolapse who underwent LAVH for benign gynaecological conditions between January 2010 and December 2019. Patients without peritoneal adhesions were compared with patients with adhesions, as diagnosed at the beginning of the procedure. Mann–Whitney-U test was used for the comparative analysis. Results Among 1,638 patients, 562 patients (34.3%) had preoperative adhesions. Main indications were for myoma (71%) and adenomyosis (14.9%). The mean operation time in the adhesion group was significantly longer than in the no-adhesion group (106 ± 44 min vs. 90 ± 35 min; p &lt; 0.001). Adhesiolysis was required in 88% within the adhesion group (n = 495). No significant differences were observed regarding mean estimated intraoperative blood loss (87 ± 100 ml vs. 90 ± 95 ml; p = 0, 418), uterine weight (220 ± 227 g vs. 230 ± 203 g; p = 0, 38), or morcellation (52% vs. 55.8%; p = 0, 142). Most patients in both groups did not experience complications (95% vs. 97.2%). Laparoconversion due to technical difficulties in performing the endocopic surgery or due to the presence of adhesions was rarely needed (1.6% vs. 0.6%). The intraoperative complication rate was low but significantly different in both groups (2% vs. 0.7%; p = 0.02), including bowel injuries (n = 6 vs. n = 3) and urinary bladder injuries (n = 4 vs. n = 5). %), which were diagnosed immediately and treated successfully. The postoperative complication rate was similar in both groups (3.4% vs. 2.1%; p = 0.138), mainly urinary tract infection. All adverse events were treated successfully; second laparoscopic surgery was conducted in five patients with adhesions and in nine patients without adhesions for haematoma removal. Conclusion LAVH could be considered a safe and feasible surgical approach for women without genital prolapse who have preoperative peritoneal adhesions and require vaginal hysterectomy for benign gynaecological conditions. This approach facilitates the localisation and treatment of adhesions at the commencement of surgery, as well as the control of possible injuries that may arise during the procedure, and is associated with a low complication rate.

Performance of International Ovarian Tumor Analysis (IOTA) predictive models in preoperative discrimination between benign and malignant adnexal lesions: preliminary outcomes in a Tertiary Care Hospital in Greece

To apply the International Ovarian Tumor Analysis (IOTA) predictive models, the logistic regression model 2 (LR2) and the IOTA Assessment of Different NEoplasias in the adneXa (ADNEX), in patients with ovarian masses and to compare their performance in preoperative discrimination between benign and malignant adnexal lesions. This was a retrospective diagnostic accuracy study with prospectively collected data, performed between January 2019 and December 2022, in a single tertiary gynecologic oncology center in Greece. The study included women with an adnexal lesion which underwent surgery within 6 months after of using the LR2 and ADNEX protocol to assess the risk of malignancy. Correlation of the ultrasound findings with the postoperative histopathological analysis was performed. Receiver-operating characteristics (ROC) curve analysis was used to determine the diagnostic accuracy of the models to classify tumors; sensitivity and specificity were determined for each model and their performance was compared. Of the136 participants, 117 (86%) had benign ovarian masses and 19 (14%) had malignant tumors. The area under the ROC curve (AUC) of the LR2 model was 0.84 (95% CI 0.74-0.93), which was significantly higher than the AUC for ADNEX model: 0.78 (95% CI 0.67-0.89). At a cut off > 10%, the LR2 model had the highest sensitivity 89.5% (95% CI 66.9-98.7) and specificity 85.1% (95% CI 76.9-91.2) compared to ADNEX model [sensitivity 84.2% (95% CI 60.4-96.6) and specificity 71.8% (95% CI 62.7-79.7)]. IOTA LR2 had the highest accuracy in differentiating between benign and malignant ovarian masses. IOTA LR2 and ADNEX models were both useful tools in discriminating between benign and malignant ovarian masses.

Does maximal effort cytoreductive surgery after 6-cycles of chemotherapy play a role in the management of advanced ovarian cancer?

The current gold standard in the surgical management of advanced ovarian cancer recommended by ESGO and ASCO is complete resection of all visible disease. If this is not deemed possible in the upfront setting, then interval cytoreductive surgery should be undertaken after 3-4-cycles of neo-adjuvant chemotherapy. Occasionally, surgery in the interval setting may not be possible either due to factors associated with patient fitness, or due to persistence of disease in sites deemed unresectable on interval scanning. Limited published data assessing outcomes from surgery delayed to after 6-cycles of NACT (delayed cytoreductive surgery) suggests a potential benefit over no surgery and suggests that if interval cytoreductive surgery is not possible, then the clinician might consider delayed surgery on a case by case basis. We sought to review the outcomes of patients with Advanced Ovarian Cancer presenting to the Northern Gynaecological Oncology Centre who underwent delayed surgery. This study is a retrospective analysis looking at patients with epithelial ovarian cancer of FIGO stage IIIC and above, who were not deemed suitable to undergo either primary or interval cytoreductive surgery, referred to the Northern Gynaecological Oncology Centre Gateshead, UK, between January 2014 and December 2020. We compared survival outcomes in women receiving non-standard treatment for advanced ovarian cancer, comparing two groups of patients; those completing at least six cycles of platinum-based chemotherapy as part of their first-line treatment and not having surgery with those who received delayed cytoreductive surgery after completing of 6-cycles of primary chemotherapy. A total of 89 cases were included in the analysis and 78/89 patients had completed at least 6-cycles of primary chemotherapy in the first-line treatment setting without any attempt at surgical cytoreduction. 11/89 patients underwent DDS after completion of 6-cycles of primary chemotherapy. The majority of included cases 87/89 (98%) were high-grade serous ovarian cancer (HGSOC). Surgery and no-surgery groups were well matched in terms of stage comparison at presentation with an overall stage distribution of 62% FIGO stage IIIC, 10% stage IVA and 28% stage IVB. The surgery group were significantly younger than the no-surgery group with median age of 68 (interquartile range (IQR) 59-71 years) and 77 years (IQR 70-82 years) (p < 0.01), respectively. The overall survival (OS) of the surgery and no-surgery groups was 25 months and 23 months, respectively (p = 0.38) with a median follow-up of 20 months (IQR 11-29 months). The 1 year disease-specific mortality for both groups was 18%. Maximal effort cytoreductive surgery after 6-cycles is not associated with a survival benefit (even with complete cytoreduction) but may be considered in the context of symptomatic disease or for palliation of symptoms amenable to surgery.

Association between pelvic inflammatory disease and risk of ovarian, uterine, cervical, and vaginal cancers—a meta-analysis

The present meta-analysis aims to investigate a potential link between pelvic inflammatory disease (PID) and an increased risk of genitourinary cancers (ovarian, cervical, uterus, and vagina cancers). While previous research has hinted at a possible link, this meta-analysis seeks to delve deeper into the available evidence. Understanding this association is crucial for preventive strategies and improving clinical management practices. A comprehensive literature search was conducted across various databases, covering studies published between 2016 and 2024. We included 13 observational studies meeting stringent criteria, followed by meticulous data extraction and quality assessment. Meta-analytical techniques were then employed to calculate pooled odds ratios (ORs), adjusted hazard ratios (HRs), and 95% confidence intervals (CIs), with heterogeneity assessed using the I Our analysis revealed significant findings, underscoring the association between PID and increased risks of genitourinary cancers. Specifically, individuals with a history of PID demonstrated notably higher odds of developing ovarian cancer (OR = 1.477, 95% CI 1.033-2.207), uterine cancer (OR = 1.263, 95% CI 0.827-2.143), cervical cancer (OR = 1.000, 95% CI 0.900-1.100), and vaginal cancer (OR = 2.500, 95% CI 1.400-4.000) compared to those without such a history. The overall heterogeneity across studies was high (I This meta-analysis provides updated evidence supporting a significant association between PID and an increased risk of cervical, ovarian, and uterine cancers. Early detection and management of PID are crucial in potentially mitigating the risk of these cancers.

Comparative effects of different treatments based on the levonorgestrel intrauterine system in endometrial carcinoma and endometrial hyperplasia patients: a network meta-analysis

Levonorgestrel intrauterine system (LNG-IUS) has been widely used in patients with endometrial carcinoma (EC), endometrial hyperplasia without atypical (EH), and atypical endometrial hyperplasia (AEH). The purpose of our Network meta-analysis (NMA) is to evaluate the efficacy of the treatments based on the LNG-IUS in patients with EC and EH with or without atypical. We examined PubMed, EMBASE, Web of Science and the Cochrane Library up to 22 April 2024 to determine studies reporting treatment outcomes in EC and EH patients receiving LNG-IUS therapy, LNG-IUS + metformin (MET), oral progestins (OP), etc. We used EndNote 9 to select studies, Jadad scale and NOS scale to assess quality, stata(16.0) and R (4.3.1) to analysis the data. Overall, 28 studies involving 3752 patients were included in our NMA. As for EH patients, LNG-IUS (RR 1.21; 95% CrI [1.11, 1.34]) and LNG-IUS + MET (RR 323.57; 95% CrI [1.61, 214,223,188.1])] significantly increased CR rate in comparison with OP. Based on SUCRA, LNG-IUS + OP was the best treatment to improve CR(SUCRA = 67.2%) in patients with EC, whereas LNG-IUS + MET was superior in increasing CR (SUCRA = 99.8%) than any other treatments for EH patients. Besides, the ranking based on SUCRA illustrated that LNG-IUS alone was the best choice to raise CR rates (SUCRA = 76.7%) for AEH patients. In head-to-head meta-analysis, OP has a higher progression rate (RR 4, 95% CI 1.89-8.46, p = 0.062; I According to the NMA, LNG-IUS related studies are feasible for conservative therapy in patients with EC and EH with or without atypical. Therefore, concerning the curative effect, we recommend LNG-IUS-based treatments as the best conservative therapy for EC and EH patients. However, future studies require large sample sizes and more outcomes to further evaluate the differences of treatment selections based on LNG-IUS.

Occult endometrial cancer in women undergoing hysterectomy for benign indications: a retrospective cohort study in a tertiary hospital in China

To evaluate the feasibility of further reducing the incidence of occult endometrial cancer in women undergoing hysterectomy for benign gynecological indications. Patients who underwent hysterectomies for presumed benign gynecologic conditions at Peking Union Medical College Hospital were retrospectively identified. Patients with occult endometrial cancer, which was defined as endometrial cancer diagnosed on postoperative histopathology with no preoperative confirmed malignancy, were selected. 24/7558 (0.32%; 95% CI 0.20-0.47%) patients undergoing hysterectomy for benign indications had occult endometrial cancer. Asymptomatic patients with normal endometrial imaging all tended to have favorable pathology. Heavy menstrual bleeding was the most overlooked AUB pattern in the premenopausal group. In the postmenopausal group, all the patients with serous adenocarcinoma or G3 endometrioid adenocarcinoma histology/stage T1b disease/LVSI space invasion had a history of persistent or recurrent PMB ≥ 6 months and/or an intracavitary lesion > 20 mm in diameter. 3/4 of the samples of the postmenopausal patients did not have adequate endometrium for evaluation. To further reduce the incidence of occult endometrial cancer, physicians should focus on the patient's bleeding pattern and actively implement endometrial sampling whenever indicated. Transvaginal ultrasonography is a valuable preoperative evaluation. Hysteroscopy with directed biopsy is the preferred procedure in postmenopausal patients.

Complete androgen insensitivity syndrome presenting with bilateral adnexal masses and mixed gonadal histopathology

Abstract Purpose Complete androgen insensitivity syndrome (CAIS) is a rare X-linked recessive disorder due to androgenreceptor mutations, characterised by a 46,XY karyotype, female phenotype, and undescended testes. This reportaims to illustrate the clinical management and the rare synchronous pathology of multiple gonadal tumors in a 60-year-old phenotypic female with long-standing CAIS. Methods A 60-year-old patient presented following the incidental detection of bilateral adnexal masses. Diagnosticevaluation included imaging (USG/MRI) to assess internal reproductive organs and gonadal morphology, alongsidehormonal analysis (LH, testosterone, and estradiol). A laparoscopic bilateral gonadectomy was performed to managethe suspected neoplasia. Results Imaging demonstrated the absence of the uterus and ovaries, confi rming bilateral solid gonadal lesions.Hormonal analysis showed elevated LH with normal testosterone and estradiol levels. Histopathology of the excisedtissues revealed a complex and heterogeneous presentation: the left gonad contained a Sertoli cell tumor, a Leydigcell tumor, and sclerotic seminiferous tubules; the right gonad showed a Sertoli cell adenoma. Conclusion This rare synchronous pathology illustrates the signifi cant heterogeneity of neoplasia associated withCAIS. Current evidence supports individualized postpubertal gonadectomy to balance the risk of malignancy againstthe benefi ts of endogenous hormonal production. The fi ndings emphasize that long-term follow-up and tailoredsurgical timing are essential components in the clinical management of CAIS.

Complex vaginal natural orifice transluminal endoscopic surgery hysterectomy for symptomatic giant polymyomatous uteri in nulliparous women

Studies on vaginal natural orifice transluminal endoscopic surgery (vNOTES), which provides enhanced endoscopic vision via the vaginal route, are limited. Therefore, this study aimed to evaluate the feasibility, safety, and perioperative outcomes of vNOTES hysterectomy in symptomatic patients with giant polymyomatous uteri and no prior vaginal delivery. A prospective single-centre case series was conducted between July 2023 and July 2025. Patients with symptomatic uterine myomatosis and a uterine size equivalent to a gestational age of ≥ 20 weeks with no prior vaginal deliveries were included. The operation time, preoperative and postoperative haemoglobin levels, uterine weight, complications, and length of hospital stay were analysed. Forty patients met the inclusion criteria. The mean operative time was 95 ± 28 min. The mean preoperative haemoglobin concentration was 11.8 ± 1.2 g/dL, whereas it was 10.9 ± 1.1 g/dL postoperatively. The mean uterine weight was 1,012 ± 312 g. The complication rate was 8%. The major complication rate was 4%. No procedures were converted to laparotomy. The median hospitalisation duration was 23.1 h. vNOTES hysterectomy appears to be a feasible minimally invasive approach for giant polymyomatous uteri in patients with no prior vaginal deliveries, with favourable perioperative outcomes in this prospective case series.

Vaginal natural orifice transluminal endoscopic surgery versus laparoscopy for ovarian cystectomy: a prospective, open-label, randomized, non-inferiority pilot trial

Vaginal natural orifice transluminal endoscopic surgery (vNOTES) is an innovative minimally invasive procedure. The study aimed to evaluate whether vNOTES achieves non-inferior results compared to conventional laparoscopy in patients undergoing ovarian cystectomy. Participants with benign ovarian tumors were randomly assigned (1:1) to undergo laparoscopy or vNOTES. Randomization was stratified based on the size of the ovarian tumor. Patients and surgeons were aware of the allocated procedures. The primary outcome was the proportion of patients successfully treated by the allocated procedure (non-inferiority hypothesis, margin of 15%). The secondary outcomes included operative time, estimated blood loss, time for specimen retrieval, postoperative pain score, use of analgesics, time to first flatus, and perioperative complications. Sixty-four patients were randomly assigned to laparoscopy (n = 32) and vNOTES (n = 32) and were included in the intention-to-treat analysis. The success rates were 100% and 96.9%, respectively. Non-inferiority of vNOTES was demonstrated, as the lower limit of the one-sided 95% confidence interval for the stratified risk difference was -12.7%, which lies above the pre-specified non-inferiority margin of -15%. The vNOTES group exhibited lower pain scores, with a median difference of -1 (95% CI -1 - -1, p < 0.001). vNOTES demonstrates non-inferiority to laparoscopy for ovarian cystectomy in selected patients, with notable advantages in cosmetic outcomes and reduced postoperative pain. ChiCTR2300070890.

FIGO 2023 staging system with/without molecular classification vs. FIGO 2009 in 172 endometrial cancer patients

To evaluate the prognostic utility of the FIGO 2023 staging system with/without molecular classification vs. FIGO 2009 in endometrial cancer. A total of 172 patients between 2015 and 2020 diagnosed with endometrial cancer in our center were included in this study. Molecular classification subtypes were classified using DNA sequencing and immunohistochemistry. The clinical characteristics and patients' prognosis were analyzed. Of the 172 patients, 10 patients were classified to the POLEmut, 30 patients to the MMRd group, 106 patients to the NSMP group, and 26 patients to the p53abn group. Stage migration from FIGO 2009 to FIGO 2023 occurred in 27.3% of the patients (47/172). Among the 47 patients, upstaging from stage I to stage II was observed in 43 patients. The transition from stage III to the early stage occurred in 2 patients, with downstaging from stage III to IA3. 9 patients were restaged as IAm disease with the FIGO 2023 m system. Downstaging to stage IAm was observed in 7 patients due to the presence of POLE mutation. In addition, 14 patients had stage IICm disease with the FIGO 2023 m. Eight patients were upstaged to stage IICm due to the presence of p53 abnormality, while 6 patients already exhibited stage IIC disease based on the FIGO 2023 classification. Patients with endometrial cancer with POLE-EDM had the best prognosis in terms of RFS and OS; those with MMRd and NSMP exhibited intermediate prognosis, with no significant difference between the two groups; and those with p53abn had the worst prognosis. Molecular classification is prognostically essential in endometrial carcinoma. The integrated FIGO 2023 m system appears to enhance risk stratification relative to FIGO 2009 and non-molecular FIGO 2023. Formal comparison of staging systems is needed to confirm this improvement.

Comparative analysis of imaging and pathological features in diagnosis of endometrial carcinosarcoma based on multimodal MRI

This case report aims to present a rare case of endometrial carcinosarcoma, a highly malignant tumor with a poor prognosis. The primary objective is to describe this unique case's clinical presentation, multimodal magnetic resonance imaging (MRI) features, typical histopathological characteristics and surgical treatment. A detailed analysis of the patient's medical history, preoperative imaging evaluation, and treatment approach was conducted. This case report includes high-resolution images and figures, showcasing MRI scans, surgical treatment, and histopathology slides related to the case. The case report outlines imaging findings of a rare case of endometrial carcinosarcoma. Multimodal imaging such as T1-weighted imaging (T1WI), T2-weighted imaging (T2WI) and multi-b-value diffusion-weighted imaging (DWI), apparent diffusion coefficient (ADC) and dynamic contrast-enhanced (DCE) scanning could accurately identify the histopathological features of the case. Surgical resection is the best treatment, and preoperative imaging evaluation should be particularly important. This case report highlights endometrial carcinosarcoma's rarity and diagnostic challenges. Multimodal MRI has significant value in diagnosing endometrial carcinosarcoma. This technology not only improves the sensitivity, specificity, and accuracy of diagnosis, but also helps to more accurately evaluate the staging and grading of tumors. By comparing imaging features and pathological results, studies have found that multimodal MRI can clearly show the anatomical structure, pathological nature, and extent of the tumor, with a high degree of consistency with the pathological diagnosis. In particular, when differentiating endometrial carcinosarcoma from low-risk endometrial cancer, multimodal MRI combined with serum carbohydrate antigen 125 (CA125) and E-box binding zinc finger protein 1 (ZEB1) detection can further improve the sensitivity and specificity of differential diagnosis. In addition, research has found that the ADC value of the tumor tissue in different pathological grades is related to the multimodal MRI, which helps to better understand the biological behavior and prognosis of the tumor. In summary, multimodal MRI is an effective diagnostic tool that can provide important evidence for the precise diagnosis and treatment of endometrial carcinosarcoma.

The impact of delay from diagnosis to surgery in endometrial cancer

When oncological waiting lists are prolonged, gynecological oncology units are forced to delay operations, especially for endometrial cancer (EC) due to its good prognosis among gynecological cancers. The aim of this study is to evaluate the impact of delay in the oncological outcomes of these patients. This is a retrospective analysis of all women with EC treated in our clinic, 2012-2019. Delay was calculated as the time interval between histological diagnosis of endometrial biopsy and definite surgery. The cutoff point was set at 8 weeks. Patients' characteristics, treatment options and follow-up information were collected. Primary outcomes were the need of adjuvant treatment and survival rates. 259 Patients met the inclusion criteria. Based on the 8-week cutoff point, patients were divided into 2 groups: 119 underwent surgery up to 8 weeks (group A) and 140 over 8 weeks (group B). There was no statistical difference in the FIGO stage or the preoperative CA-125 levels between the two groups. However, patients in group A were younger, with lower body mass index (BMI) and less comorbidities. Furthermore, patients in group B had a significantly higher probability of receiving pelvic radiation with or without brachytherapy (p = 0.0053). Concerning survival rates, there was a statistically difference in disease-free (p = 0.0312), but no difference was found in overall survival (p = 0.146). Delaying EC surgery over 8 weeks may not have an impact on the mortality of the patients, but increases the need of adjuvant pelvic radiation and worsens recurrence rates. As a result, patients experience more side effects which subsequently had negative impact on their quality of life.

First-degree family history of cancers in patients with stage I endometrial carcinoma. Prevalence and prognostic impact

We aimed to study the impact of first-degree family history on patients with endometrial cancer. We conducted a retrospective chart review from January 1990 to June 2016, comparing stage I endometrial cancer patients with and without a sporadic family history of cancers. We collected the patients' demographic information, tumor characteristics, and treatment plans. During the follow-up period, patient information on tumor recurrence and survival was collected. The chi-square test was used to assess the associations between categorical variables. The Cox proportional hazards regression model was used to estimate multivariate-adjusted hazard ratios (95% confidence interval (CI)). Among the 1737 patients with stage I endometrial cancer, 709 had a positive first-degree family history of cancers and 1028 had negative family history (FH) of cancers. Patients with positive FH were more likely to be older, have stage IB disease, and receive adjuvant radiotherapy; however, the difference was not statistically significant. At 5 years follow up, patients with a positive family history had longer time to recurrence (TTR) than their negative FH counterparts. Maternal family history of cancer was the most common, followed by a sister's history of cancer, paternal history, brother's history, and offspring history of cancer. Breast, endometrial, and colon cancers are the most common cancers among first-degree relatives. Endometrial cancer patients with sporadic first-degree FH of cancers share similar demographics and tumor characteristics compared to their counterpart with slightly increased likelihood to be older, with stage IB disease and have a longer TTR compared to their negative counterpart.

Comparing oncological outcomes of robotic versus open surgery in the treatment of endometrial cancer

Robotic surgery has been incorporated in the treatment of endometrial cancer, with evidence suggesting that minimal access surgery offers advantages over laparotomy including less blood loss, lower rate of perioperative complications, and accelerated postoperative recovery. The laparoscopic approach to cervical cancer (LACC) study has recently demonstrated inferior survival outcomes in cervical cancer patients treated with minimal access surgery including robotic surgery. It is, therefore, imperative that further evaluation of the latter in endometrial cancer is performed. A retrospective analysis of clinical data was performed. We compared two different types of surgery performed for the treatment of FIGO stage 1 to 3 endometrial cancer; open surgery performed in the years 2013-2015 vs robotic surgery performed in 2017-2019, after the implementation of the robotic program in our institution. Main outcome measures were recurrence-free survival and overall survival, with secondary outcomes including surgical morbidity and postoperative recovery. We compared 123 patients who had open surgery with 104 patients who underwent robotic surgery. One case from the second group was converted to open surgery due to the inability to complete it robotically. After a median follow-up of 68 months, there was no difference in recurrence-free survival or overall survival between the two groups. Length of stay after an operation was significantly different with mean hospital stay of 1.6 days after robotic surgery and 5 days after open surgery (p = 0.001). No significant difference was identified in the rate of complications (p = 0.304). Our analysis has demonstrated that robotic surgery offers better perioperative outcomes without compromising the oncological safety.

Comparison of sentinel lymph node distribution and lymphatic drainage pathway between high- and low-risk endometrial cancers

This study aimed to compare the distribution and drainage pathway of sentinel lymph nodes between high- and low-risk endometrial cancers. In total, 429 patients with endometrial cancer who underwent sentinel lymph node biopsy in Peking University People's Hospital from July 2015 to April 2022 were retrospectively enrolled. There were 148 patients in the high-risk group and 281 patients in the low-risk group. The unilateral and bilateral detection rates of sentinel lymph nodes were 86.5% and 55.9%, respectively. The highest detection rate was achieved in the subgroup with a combined use of indocyanine green (ICG) and carbon nanoparticles (CNP) (94.4% for unilateral detection and 66.7% for bilateral detection). The upper paracervical pathway (UPP) was detected in 93.3% of cases in the high-risk group and 96.0% of cases in the low-risk group (p = 0.261). The lower paracervical pathway (LPP) was detected in 10.0% of cases in the high-risk group and 17.9% of cases in the low-risk group (p = 0.048). Remarkably increased detection rates of SLN in the common iliac (7.5%) and para-aortic or precaval areas (2.9%) were observed in the high-risk group. In contrast, a markedly decreased detection rate of SLN in the internal iliac area (1.9%) was observed in the high-risk group. The highest detection rate of SLN was observed in the subgroup with a combined use of ICG and CNP. The detection of UPP is important for both high-risk and low-risk cases, while LPP detection plays a more important role in the low-risk group. Lymphadenectomy in the common iliac and para-aortic or precaval areas is essential for patients with high-risk EC. Removal of internal iliac lymph nodes is essential for patients with low-risk EC, in case of ineffective SLN mapping.

Evolving trends in the surgical therapy of patients with endometrial cancer in Germany: analysis of a nationwide registry with special emphasis on perioperative outcomes

Abstract Purpose Endometrial cancer (EC) is the most common gynecological malignancy in women, with increasing incidence in the last decades. Surgical therapy is the mainstay of the initial management. The present study analyzed the evolving trends of surgical therapy in Germany in patients diagnosed with EC recorded in a nationwide registry. Methods All patients with the diagnosis of EC undergoing open surgery, laparoscopic surgery, and robotic-assisted laparoscopic surgery between 2007 and 2018 were identified by international classification of diseases (ICD) or specific operational codes (OPS) within the database of the German federal bureau of statistics. Results A total of 85,204 patients underwent surgical therapy for EC. Beginning with 2013, minimal-invasive surgical therapy was the leading approach for patients with EC. Open surgery was associated with a higher risk of in-hospital mortality (1.3% vs. 0.2%, p  &lt; 0.001), of prolonged mechanical ventilation (1.3% vs. 0.2%, p  &lt; 0.001), and of prolonged hospital stay (13.7 ± 10.2 days vs. 7.2 ± 5.3 days, p  &lt; 0.001) compared to laparoscopic surgery. A total of 1551 (0.04%) patients undergoing laparoscopic surgery were converted to laparotomy. Procedure costs were highest for laparotomy, followed by robotic-assisted laparoscopy and laparoscopy (8286 ± 7533€ vs. 7083 ± 3893€ vs. 6047 ± 3509€, p  &lt; 0.001). Conclusion The present study revealed that minimal-invasive surgery has increasingly become the standard surgical procedure for patients with EC in Germany. Furthermore, minimal-invasive surgery had superior in-hospital outcomes compared to laparotomy. Moreover, the use of robotic-assisted laparoscopic surgery is increasing, with a comparable in-hospital safety profile to conventional laparoscopy.

Relationship between molecular markers and lymphadenectomy and lymphovascular space invasion in endometrial cancer

Relationship between pathologic parameters, surgical parameters, or lymph node status with oncologic outcomes is not fully elucidated in endometrial cancer (EC). We want to investigate the molecular classification of uterine cancer in the Turkish population and its relationship between lymphadenectomy and lymph node metastasis. In this study, 100 patients' clinical and pathologic data diagnosed with EC were analyzed. Pathologic and molecular parameters were investigated and compared them with clinical parameters. According to the molecular analysis, 16 patients (16%) had p53 mutation, 3 patients (3%) were classified as POLE mutant group, 38 (38%) patients in the MSI group, and the remaining 43 patients (43%) into the no specific mutation profile (NSMP) group. Lymph node metastasis rate was significantly higher in copy number high (CNH) group compared to the others. In the CNH group, 29 of 437 (6.6%) dissected lymph nodes had metastasis. The median OS was the highest in the POLE group (72 months) and lowest in the CNH group (36 months). Endometrial cancer patients showed significantly different overall and disease-free survival according to the molecular subtypes and it was consistent with the literature, Lymph node metastasis risk was the highest in CNH group. MSI status is important for the lymph node metastasis risk but not all abnormalities, especially PMS2 and MLH1 expression changes showed the highest risk.

Circ_0002577/miR-126-5p/MACC1 axis promotes endometrial carcinoma progression by regulation of proliferation, migration, invasion, and apoptosis of endometrial carcinoma cells

Endometrial carcinoma (EC) is a common female reproductive malignant tumor. Circular RNAs (circRNAs) have been reported to participate in tumorigenesis, including EC. Therefore, this study was designed to clarify the role and underlying molecular mechanisms of circ_0002577 in EC. The expression levels of circ_0002577, miR-126-5p, and metastasis associated in colon cancer 1 (MACC1) was determined by real-time quantitative polymerase chain reaction (RT-qPCR) assay. The protein expression was quantified by western blot assay. The proliferation of EC cells was assessed by 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyl-2H-tetrazol-3-ium bromide (MTT) and colony-forming assays. The migration and invasion of EC cells was measured by transwell assay. The apoptosis was determined by flow cytometry assay. Dual-luciferase reporter assay and RNA pull-down assays were performed to confirm the relationship between miR-126-5p and circ_0002577 or MACC1. The influence of circ_0002577 inhibition on tumor growth was assessed by xenograft experiment. Circ_0002577 and MACC1 were increased while miR-126-5p was decreased in EC tissues and cells. Loss-of-functional experiment revealed that silencing of circ_0002577 inhibited the proliferation, migration, and invasion while induced apoptosis of EC cells, which were overturned by overexpression of MACC1. The upregulation of miR-126-5p also impeded proliferation and mobility while induced apoptosis of EC cells. MiR-126-5p, negatively regulating MACC1 expression, was a functional target of circ_0002577 in EC cells. Moreover, we also confirmed that suppression of circ_0002577 repressed tumor growth in vivo. The contributions of the circ_0002577 in EC were contributed to its interactions with miR-126-5p and MACC1, which offered a new perspective to the roles of circ_0002577 in EC.

The relationship between endometrial thickening and endometrial lesions in postmenopausal women

The study aims to investigate the relationship between endometrial thickening and endometrial lesions in postmenopausal women. Totally 390 postmenopausal patients with endometrial thickening ≥ 5 mm were enrolled from June 2016 to April 2020, among whom 188 patients were asymptomatic and 202 patients were symptomatic. There were 50 cases with endometrial cancer and precancerous lesions and 150 cases with benign lesions in the symptomatic group, significantly higher than that in the asymptomatic group. The most common pathological type in the asymptomatic group was endometrial polyp. In the asymptomatic group, statistically significant differences were found in endometrial thickness between patients with endometrial cancer and precancerous lesion (group B) and those with benign lesions and non-organic lesions (group A). Statistically significant differences were also found in age, endometrial thickness, hypertension, full-term delivery time and miscarriage times between group A and group B. Regression analysis indicated that hypertension and endometrial thickness were independent risk factors for endometrial cancer and precancerous lesions in the symptomatic group. ROC analysis showed that 10.5 mm was the optimal threshold for predicting endometrial cancer and precancerous lesions in the asymptomatic group, with sensitivity of 100% and specificity of 78.3%. The incidence of endometrial cancer and precancerous lesions in postmenopausal women with endometrial thickening and vaginal bleeding is higher than that of asymptomatic women. The endometrial thickening in postmenopausal asymptomatic women is mainly benign, and the threshold for predicting endometrial cancer and precancerous lesions is 10.5 mm.

The significance of “atrophic endometrium” in women with postmenopausal bleeding

We evaluated the interpretation of atrophic endometrium (AE) histology as the most common cause for postmenopausal bleeding (PMB). This theory has been accepted for several generations by gynecologists and gynecologic oncologists and has been published in past and current major gynecology textbooks. In our review of the literature, we did not find sufficient histological or clinical proof for this concept. In our view, AE is not a cause of PMB and we back this up with a review of old and current medical literature. The old studies are based on information which was obtained prior to the existence of transvaginal sonogram, sonohysterogram and hysteroscopy. Focal lesions are notorious for being missed by endometrial sampling and curettage. Recent studies show that focal endometrial lesions are a crucial cause for PMB and some of those lesions can harbor cancer. In our opinion, AE is the most common histology found because it is physiologic and a ubiquitous finding in postmenopausal women, but it is not a cause of PMB. Referring to AE as a cause of PMB may result in misdiagnosis of cancer, management delay and unnecessary intervention. To avoid misdiagnosis of cancer, transvaginal sonogram should be considered in all women with PMB and AE on pathology. If endometrial thickness is found, AE is unlikely to be the cause of the PMB and further workup is warranted to reveal the true etiology for the bleeding.

Fertility sparing treatment in patients with endometrial cancer (FERT-ENC): a multicentric retrospective study from the Spanish Investigational Network Gynecologic Oncology Group (SPAIN-GOG)

The primary objective was to evaluate the response rate of conservative treatment for endometrial cancer, and the secondary objective was to assess oncological, fertility and obstetric outcomes in patients who underwent fertility preservation treatment. This multicentre, observational, retrospective study evaluated endometrial cancer patients who underwent fertility-sparing treatment in Spanish centres between January 2010 and January 2020. Seventy-three patients with stage IA endometrioid adenocarcinoma of the uterus were included in the study. The levonorgestrel intrauterine device (LNG-IUD) was the most common fertility-sparing treatment (53.4%), followed by megestrol acetate (20.5%) and medroxyprogesterone acetate (16.4%). During the 24-month follow-up period, the rate of complete response to fertility-sparing management was 74% (n = 54), and 8.2% (n = 6) of patients presented a partial response. Additionally, 13 (17.8%) patients presented with persistent disease and six (8.2%) relapsed after response. The LNG-IUD was associated with a higher complete response rate than the other methods (87.2 vs. 58.8%; p = 0.01). Surgical treatment (at least hysterectomy) was performed in 44 (60.3%) patients as the end of fertility-sparing treatment. Four (5.5%) patients presented relapse after surgery, associated with final FIGO stage III (p = 0.036), myometrial invasion > 50% (p = 0.018) and final tumour grade 2-3 (p = 0.018). The mean follow-up period was 57.8 (range 6-159) months. The 5-year relapse-free survival and overall survival rates were 92.6% [95% CI (81.3, 97.2)] and 93.5% [95% CI (80.7, 97.9)], respectively. During follow-up, three patients (4.1%) died of the disease after completion of surgical treatment. Up to 50.7% of patients included in the study attempted to get pregnant. Of these, the rate of pregnancy was 81.1% (n = 30/37), and reproductive techniques were used for this purpose in 78.4% of cases. Fertility-sparing management presented a high response rate in patients with endometrial cancer. LNG-IUD was associated with a better response rate compared to the other treatment options. Moreover, in patients using this management method, pregnancy could be achieved using reproductive techniques.

The optimal time for the initiation of in vitro fertilization and embryo transfer among women with atypical endometrial hyperplasia and endometrial carcinoma receiving fertility-sparing treatment

To explore the optimal time for initiating in vitro fertilization and embryo transfer (IVF-ET) in women with complete remission after fertility-sparing treatment for grade I endometrial cancer (EC) or atypical endometrial hyperplasia (AEH). Young women who demonstrated complete remission after fertility-sparing treatment for grade I EC or AEH and underwent IVF-ET treatment were included. A generalized estimating equation (GEE) was used to compare the outcomes of controlled ovarian hyperstimulation (COH) and embryo transfer at different times after discontinuing high-dose progesterone therapy, and patients were divided into three groups: ≤ 3 months (time 1), 3-9 months (time 2) and > 9 months (time 3). Thirty-seven women with complete remission after fertility-sparing treatment for grade I EC or AEH underwent 75 IVF-ET cycles. Regarding initiation of COH, 10 cycles for time 1, 31 cycles for time 2 and 34 cycles for time 3 were included. The odds ratios (95% confidence intervals) for the number of available embryos at time 2 and time 3 were 1.82 (1.08-3.08) and 2.45 (1.39-4.33), and those for the number of high-quality embryos at time 2 and time 3 were, respectively, 3.64 (1.34-9.87) and 3.62 (1.10-11.91), compared with that at time 1. Nineteen (51.4%) women had at least one clinical pregnancy and 13 (35.1%) women had live births. During a median follow-up period of 51 months (range 5-168 months), 10 (27.0%) women had disease relapse, with a median interval of 15.5 months (range 5-104 months). Initiating IVF-ET 3 months after ceasing high-dose progesterone therapy can lead to better outcomes of controlled ovarian hyperstimulation for women with endometrial cancer or atypical endometrial hyperplasia.

High-grade endometrial stromal sarcoma versus undifferentiated uterine sarcoma: a Turkish uterine sarcoma group study-001

Prognostic factors associated with high-grade endometrial stromal sarcoma (HGESS) and undifferentiated uterine sarcoma (UUS) have not been distinctly determined due to the repetitive changes in the World Health Organization (WHO) classification. We aimed to compare clinicopathologic features and outcomes of patients with HGESS with those of patients with UUS. A multi-institutional, retrospective, cohort study was conducted including 71 patients, who underwent surgery at 13 centers from 2008 to 2017. An experienced gynecopathologist from each institution re-evaluated the slides of their own cases according to the WHO The median disease-free survival (DFS) for HGESS and UUS was 12 months and 6 months, respectively. While the median overall survival was not reached in HGESS group, it was 22 months in the UUS group. Kaplan-Meier analyses revealed that patients with UUS had a significantly poorer DFS than those with HGESS (p = 0.016), although OS did not differ between the groups (p = 0.135). Lymphovascular-space involvement (LVSI) was the sole significant factor associated with progression, recurrence or death for HGESS (Hazard ratio: 9.353, 95% confidence interval: 2.539-34.457, p = 0.001), whereas no significant independent factor was found for UUS. UUS has a more aggressive behavior than HGESS. While no significant predictor of prognosis was found for UUS, LVSI is the sole independent prognostic factor for HGESS, with patients 9.3 times more likely to experience refractory/progressive disease, recurrence or death.

Developing a validated nomogram for predicting ovarian metastasis in endometrial cancer patients: a retrospective research

To explore risk factors and develop a prediction model for ovarian metastasis in endometrial cancer (EC), as well as providing provide a reference for clinical ovarian preservation. We conducted a retrospective observational study enrolling 1496 EC patients having received complete staging surgery from Qilu Hospital of Shandong University from 2012 to 2018. These patients were randomly divided into two cohorts: training cohort (n = 1046) and validation cohort (n = 448). A nomogram prediction model was developed based on univariate, least absolute shrinkage and selection operator (Lasso), and multivariate logistic regression. Then, the nomogram model's performance was evaluated in discrimination, calibration, and clinical utility three aspects. Parametrium invasion, lymph node metastasis, and oviduct metastasis were finally contained in the nomogram prediction model. The AUC of the model in the training cohort was 0.85 compared with 0.72 in the validation cohort. It also behaved well in calibration and had good clinical utility. With a threshold probability of 20% ~ 80%, the nomogram increased the net benefit by 0 ~ 13.6 per 100 patients than surgery for all patients upon validation. We develop a nomogram with good performances for predicting ovarian metastasis in EC patients, which may help clinicians identify candidate patients appropriate for ovarian preservation in premenopausal EC patients.

Survival outcomes of women with grade 3 endometrioid endometrial cancer: the impact of adjuvant treatment strategies

This multicenter investigation was performed to evaluate the adjuvant treatment options, prognostic factors, and patterns of recurrence in patients with grade 3 endometrioid endometrial cancer (G3-EEC). The medical reports of patients undergoing at least total hysterectomy and salpingo-oophorectomy for G3-EEC between 1996 and 2018 at 11 gynecological oncology centers were analyzed. Optimal surgery was defined as removal of all disease except for residual nodules with a maximum diameter ≤ 1 cm, as determined at completion of the primary operation. Adequate systematic lymphadenectomy was defined as the removal of at least 15 pelvic and at least 5 paraaortic LNs. The study population consists of 465 women with G3-EEC. The 5-year disease-free survival (DFS) and overall survival (OS) rates of the entire cohort are 50.3% and 57.6%, respectively. Adequate systematic lymphadenectomy was achieved in 429 (92.2%) patients. Optimal surgery was achieved in 135 (75.0%) patients in advanced stage. Inadequate lymphadenectomy (DFS; HR 3.4, 95% CI 3.0-5.6; P = 0.016-OS; HR 3.2, 95% CI 1.6-6.5; P = 0.019) was independent prognostic factors for 5-year DFS and OS. Inadequate lymphadenectomy and LVSI were independent prognostic factors for worse DFS and OS in women with stage I-II G3-EEC. Adequate lymphadenectomy and optimal surgery were independent prognostic factors for better DFS and OS in women with stage III-IV G3-EEC.

Silencing YKL-40 gene can inhibit inflammatory factor expression and affects the effect of THP-1 cells on endometrial cancer

To investigate the effect of silencing the YKL-40 gene on the expression of inflammatory factors and the effect of silencing the YKL-40 gene of THP-1 cells on endometrial cancer. We used a siRNA targeting a sequence in YKL-40 (si-YKL-40) to transfect HEC-1A and THP-1 cells. Quantitative real-time polymerase chain reaction assay was performed to investigate the mRNA levels of YKL-40, IL-8 and MMP-9 in HEC-1A and THP-1 cells. Migration, and invasion assays were performed to identify the effects of co-culture with THP-1 cells that silenced YKL-40 gene on the migration and invasion capacity of HEC-1A cells. Tube formation ability were detected by Matrigel-based angiogenesis assay. We successfully transfected HEC-1A and THP-1 cells with lentivirus to silence the YKL-40 gene. Compared with the blank control group and NC group, the expression of YKL-40, IL-8 and MMP-9 which were examined by qRT-PCR in YKL-40-siRNA group was significantly reduced in the two cell lines; after co-cultured with the supernatant of transfected THP-1 cells, the migration and invasion ability of HEC-1A cells in YKL-40-siRNA group was significantly reduced; the number of tubes in the YKL-40-siRNA group was significantly reduced, the spacing between the tubes was significantly increased, and the structure of tubes was incomplete. Silencing the YKL-40 gene in THP-1 cells can inhibit the expression of inflammatory factors, the invasion and migration of human endometrial cancer cells and the capacity of vitro angiogenic. And YKL-40 gene as a marker of inflammation may be an effective therapeutic target for endometrial cancer.

Lymphovascular space invasion as a prognostic factor of epithelial ovarian cancer: a multicenter study by the FRANCOGYN group

The presence of lymphovascular space invasion (LVSI) is not yet included in international recommendations neither as a prognostic factor nor as a parameter for the decision to use adjuvant chemotherapy in FIGO stage I/IIa ovarian cancer (OC). This study set out to evaluate the impact of LVSI on Overall Survival (OS) and Recurrence-Free Survival (RFS) in patients managed for epithelial OC. Retrospective multicenter study by the research group FRANCOGYN between January 2001 and December 2018. All patients managed for epithelial OC surgery and for whom histological slides for the review of LVSI were available, were included. The characteristics of patients with LVSI (LVSI group) were compared to those without LVSI (No-LVSI group). A Cox analysis for OS and RFS analysis was performed in all the populations. French multicenter tertiary care centers RESULTS: Over the study period, 852 patients were included in the 13 institutions. Among them, 289 patients had LVSI (33.9%). There was a significant difference in the distribution of LVSI between early and advanced stages (p  <  0.001). LVSI was an independent predictive factor for poorer Overall and Recurrence-Free Survival. LVSI affected OS (p  <  0.001) and RFS (p  <  0.001), LVSI affected OS and RFS for early stages (p  =  0.001; p  =  0.001, respectively) and also for advanced stages (p  =  0.01; p  =  0.009, respectively). The presence of LVSI in epithelial ovarian epithelial tumors has an impact on OS and RFS and should be included in the routine pathology examination to adapt therapeutic management, especially for women in the early stages of the disease.

Association of preoperative serum HE4 levels on the survival of patients with endometrial cancer

To evaluate the association between preoperative serum human epididymis protein 4 (HE4) levels and survival outcomes in endometrial cancer (EC) patients. A retrospective cohort study was conducted of EC patients who were scheduled for surgery between September 2013 and May 2014 at Rajavithi Hospital. Association between preoperative serum HE4 levels and clinicopathological characteristics were evaluated. Cox proportional-hazards model was used to compare overall survival (OS) and recurrence-free survival (RFS) between EC patients who had high serum HE4 levels and those who did not. A total of 86 EC patients were enrolled. Serum HE4 levels was significantly associated with older age (p < 0.001), postmenopausal women (p = 0.001), large tumor size (p < 0.001), presence of lymphovascular invasion (p = 0.022), deep myometrial invasion (p = 0.001), lymph node metastasis (0.017), high-risk group (p < 0.001), and death status (p = 0.002). With a median follow-up of 53 months, the 3-years OS and PFS of EC patients who had high serum HE4 levels were significantly poorer than those who did not (71% vs 95.8%, and 67.7% vs 91.7%, respectively). A high serum HE4 level was a significant prognostic factor for OS and RFS from the univariate analysis. However, it was not a significant prognostic factor in the multivariate analysis. Preoperative high serum HE4 levels were significantly associated with the worse clinicopathological characteristic of EC patients and decreased OS and RFS. Although there was no strong independent prognostic factor for survival, serum HE4 levels could be used in an algorithm for stratifying high-risk EC patients with more proper management.

The use of hysteroscopic endometrectomy in the conservative treatment of early endometrial cancer and atypical hyperplasia in fertile women

To illustrate the effectiveness of hysteroscopic endometrial resection in conservative treatment of early endometrial cancer/atypical hyperplasia in women of reproductive age. Review of outcomes of women of reproductive age who underwent fertility sparing treatment (hysteroscopic superficial endometrectomy followed by progestin therapy) in early endometrial cancer. Eight women with Stage I endometrial cancer and three with atypical endometrial hyperplasia underwent hysteroscopic superficial endometrial resection, followed by 1-year treatment with oral megestrol acetate. One patient had a synchronous endometrioid ovarian carcinoma. One patient with Grade 2 carcinoma opted for conservative treatment and had hysterectomy 3 months later for persisting disease. Ten patients showed no evidence of residual disease during a 12-month follow-up period with regular hysteroscopy. Five patients had seven pregnancies without assisted reproductive technology. One patient got pregnant after one attempt of in-vitro fertilization and oocyte donation. Pregnancy rate was 54.5%; two patients had two successful pregnancies and deliveries. Average time to pregnancy was 16 months from the end of treatment. All babies were delivered vaginally. Total superficial endometrial resection followed by progestin can be considered in patients with early endometrial cancer/atypical hyperplasia who still want to conceive. It does not seem to impair fertility nor pregnancy outcomes in women of reproductive age.

Association between BRCA mutations and endometrial carcinoma: a systematic review with meta-analysis

To first investigate on the association between BRCA mutations and endometrial carcinoma. To first evaluate the contribution of tamoxifen use and risk-reducing bilateral salping-oophenrectomy (BSO) on endometrial carcinoma in BRCA carriers. A systematic search of electronic databases including the PubMed and EMBASE was conducted to identify publications exploring the association between BRCA mutations and endometrial carcinoma. Finally, single rate meta-analysis and diagnostic meta-analysis were performed. 11 retrospective studies and 3 prospective studies were included in the meta-analysis, single rate meta-analysis was performed on retrospective studies and prospective studies respectively. We got that incidence of BRCA mutations in patients with endometrial carcinoma is about 0.035, the incidence of endometrial carcinoma in BRCA carriers is about 0.004. Diagnostic meta-analysis performed on prospective studies found that tamoxifen increased incidence of endometrial carcinoma in BRCA carriers. The incidence of BRCA mutations in patients with endometrial carcinoma is about 0.035 according to present studies, the incidence of endometrial carcinoma in BRCA carriers is about 0.004. Tamoxifen use is a certain risk factor for subsequent endometrial carcinoma, while history of breast cancer or risk-reducing BSO is not associated with incidence of follow-up endometrial carcinoma. The necessity and rationality of prophylactic hysterectomy for BRCA carriers remained to be discussed.

Accuracy of intra-operative frozen section in guiding surgical staging of endometrial cancer

Surgery consists the main treatment of endometrial cancer; however, decision of lypmhadenectomy is controversial. Intra-operative frozen section (FS) is commonly used in guiding surgical staging; nevertheless, there are different reports regarding its adequacy and reliability. Aim of this study is to assess accuracy of FS in predicting paraffin section (PS) results in patients with endometrium cancer. Data of 223 cases, who were operated for endometrial cancer at a tertiary hospital in 2012-2019, were analyzed retrospectively. Histological type, grade, tumor diameter, depth of myometrial invasion, and cervical and adnexal involvement in frozen and paraffin section were evaluated. Positive and negative predictive values and accuracy of frozen results in predicting paraffin results for each parameter was assessed. Statistical significance was taken as 0.05 in all tests. Accuracy of FS in predicting PS results were 76.23% for histology, 75.45% for grade, 85.31% for depth of myometrial invasion, and 95.45% for tumor diameter. Surgery, based on FS results, caused undertreatment in 4 patients, while metastatic lymph node ratios were found in only 35.3-50.0% of cases who had high risk parameters at FS. Our FS results have reasonable accuracy rates in predicting PS results, in comparison with the previous literature. However, even if the high risk parameters detected in FS predict PS accurately, absence of lymph node involvement in all cases with high risk parameters indicates that FS-based triage cannot prevent unnecessary lymphadenectomies.

International trends in ovarian cancer incidence from 1973 to 2012

Ovarian cancer is the 7th leading cancer diagnosis and the 8th leading cause of cancer death in women worldwide. We conducted this study to investigate the incidence of ovarian cancer internationally. The trends in ovarian cancer incidence were analyzed through the latest data of CI5 over the 40-year period from 21 populations in 4 continents using Joinpoint analysis, ASRs and proportions of different histological subtypes in those populations were also analyzed using volume XI of CI5. ASRs of ovarian cancer were from 7.0 to 11.6 per 100,000 in non-Asia populations during 2008-2012. In Asia, the ASR in Israel (Jews) were the highest, up to 8.1 per 100,000 in the same period. The international trends from 1973 to 2012 showed that ASRs of ovarian cancer were decreasing in 8 of 21 selected populations, whereas ASRs in Slovakia, Spain (Navarra) and China (Shanghai) were increasing. Meanwhile, there are certain differences in the main pathological classification patterns within different regions. In Asia, China (Hong Kong) and Japan both have a higher ASRs and proportions for clear cell and endometrioid carcinomas, while Japan has the highest ASRs and proportions for mucinous carcinomas. Although the reasons for those trends were not entirely clear, environmental, reproductive and genetic factors were likely to have led to these patterns. Meanwhile, more attention and further study should be given to the etiological factors of histology-specific ovarian cancer.

Circular RNA circ_0000043 promotes endometrial carcinoma progression by regulating miR-1271-5p/CTNND1 axis

Circular RNAs (circRNAs) are involved in a variety of biological processes, including tumorigenesis. However, the exact role and molecular mechanisms of circ_0000043 in endometrial carcinoma (EC) remain largely unknown. Quantitative real-time polymerase chain reaction (qRT-PCR) was carried out to determine the expression levels of circ_0000043, microRNA-1271-5p (miR-1271-5p) and catenin delta 1 (CTNND1). 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and flow cytometry were used to measure cell proliferation, cell apoptosis and cell cycle distribution, respectively. Cell migration and invasion were assessed by transwell assay. Western blot assay was performed to examine the protein expression of matrix metalloproteinase 2 (MMP2), MMP9 and CTNND1. The interaction between miR-1271-5p and circ_0000043 or CTNND1 was predicted by starBase and confirmed by dual-luciferase reporter assay. The mice xenograft model was established to investigate the role of circ_0000043 in vivo. Circ_0000043 and CTNND1 were highly expressed and miR-1271-5p was lowly expressed in EC tissues and cells. Knockdown of circ_0000043 inhibited the progression of EC by inhibiting cell proliferation, migration, invasion and tumor growth (in vivo) and promoting apoptosis. MiR-1271-5p was a direct target of circ_0000043 and its inhibition reversed the inhibitory effect of circ_0000043 knockdown on the progression of EC cells. In addition, CTNND1 was a downstream target of miR-1271-5p, and miR-1271-5p overexpression inhibited EC cell proliferation, migration and invasion and induced apoptosis by targeting CTNND1. Moreover, circ_0000043 positively regulated CTNND1 expression by sponging miR-1271-5p. Circ_0000043 knockdown inhibited the progression of EC by regulating miR-1271-5p/CTNND1 axis, which might provide a promising circRNA-targeted therapy for EC.

Comparison of survival of patients with endometrial cancer undergoing sentinel node biopsy alone or systematic lymphadenectomy

Recently, sentinel lymph node mapping was introduced in the surgical staging of endometrial cancer as alternative to systematic lymphadenectomy. However, the survival impact of sentinel node mapping is not well characterized yet. We performed retrospective study of 104 patients with endometrial cancer treated with sentinel lymph node alone (n = 52) or with pelvic and para-aortic lymphadenectomy (n = 52). For sentinel node mapping, indocyanine green was used. The outcome measure was disease-free survival. Median follow-up was 42 months. Fifty-two patients staged by sentinel lymph node mapping were matched in 1:1 ratio with 52 patients staged by lymphadenectomy using patient age, histological type, tumor stage, tumor grade and lymph and vascular space invasion as matching criteria. The median number of removed lymph node was 3 (range 1-6) and 36 (13-63) in the sentinel and lymphadenectomy group, respectively. The rate of lymph node metastases was not significantly higher in the sentinel group (19.2%) in comparison with the lymphadenectomy group (14.3%). The overall detection rate of sentinel lymph nodes was 100% with a bilateral mapping of 98.1%. Most of the 152 lymph nodes identified and removed were localized in upper paracervical pathway (n = 143, 94.1%). During the follow-up period, overall 21 (20.2%) events were observed, 8 (15.4%) in the sentinel group and 13 (25.0%) in the lymphadenectomy group. The estimated disease-free survival was 84.6% and 75.0% for patients in the sentinel and lymphadenectomy groups, respectively. The survival curves demonstrated similar disease-free survival in two groups (p = 0.774). Sentinel lymph node mapping did not compromise the outcome of patients with endometrial cancer.

Combined pelvic and para-aortic is superior to only pelvic lymphadenectomy in intermediate and high-risk endometrial cancer: a systematic review and meta-analysis

Lymph node metastasis is a principal prognostic factor for the treatment of endometrial cancer. Added value of para-aortic lymphadenectomy to only pelvic lymphadenectomy for intermediate/high-risk endometrial cancer patients remains controversial. A systematic review and meta-analysis was performed to assess the impact of combined pelvic and para-aortic lymph node dissection (PPALND) compared to only pelvic lymph node dissection (PLND) on survival outcomes of intermediate and/or high-risk patients. The systematic review and meta-analysis adhered to the PRISMA guidelines for meta-analyses of interventional studies. Pubmed, Scopus, EMBASE and Cochrane were searched up to April 20, 2018. Included studies were those comparing high-risk endometrial cancer patients that had performed pelvic and para-aortic lymph node dissection (PPALND) vs. only pelvic lymph node dissection (PLND) apart from standard procedure (total hysterectomy with bilateral salpingo-oophorectomy, TAHBSO). Primary outcomes of the study were overall survival and disease-free survival rates. Methodological quality of the included studies was assessed using the ROBINS-I tool. Overall quality of the evidence for the primary and secondary outcomes was evaluated as per GRADE guideline using the GRADE pro GD tool. There were 13 studies identified with 7349 patients included. All studies were retrospective observational as no RCTs or prospective studies adhering to inclusion criteria were retrieved. Combined pelvic and para-aortic lymphadenectomy was associated with 46% decreased risk for death (HR 0.54, 95% CI 0.35-0.83, I Combined pelvic and para-aortic lymphadenectomy is associated with improved survival outcomes compared with only pelvic lymphadenectomy in women with intermediate/high-risk endometrial cancers. Further prospective studies should be performed.

Systematic lymphadenectomy in early stage endometrial cancer

The positive effect of systematic lymphadenectomy on survival of patients with endometrial cancer is a topic of ongoing debate. We aimed to investigate whether systemic lymphadenectomy is beneficial for patients with early endometrial cancer. For this purpose, we analyzed a population-based registry with of 2392 women with endometrioid endometrial cancer, stage I and II at intermediate and high risk of recurrence. The primary outcome measure was overall survival. After exclusions, 868 women were eligible for analysis. Of those, 511 and 357 were categorized as intermediate (pT1A G3 and pT1B G1-2) and high risk (pT1B G3 and pT2 G1-3) early stage endometrial cancer, respectively. Lymphadenectomy was performed in 527 (60.7%) of the cases. Patients in the lymphadenectomy group were significantly younger, presented with more tumors of intermediate or undifferentiated grade and exhibited significantly lower co-morbidity rates and Eastern Cooperative of Oncology Group (ECOG) performance status. Median follow-up was 6.7 years. Recurrence-free survival was not improved by lymphadenectomy in the intermediate and high-risk group of patients. During the follow-up period, 111 (12.8%) women had disease recurrence and 302 (34.8%) died. Systematic lymphadenectomy was associated with significant improvement of overall survival in the pT1A G3 and pT1B G3 patient subgroups. Notably, adjustment for patient age and ECOG status abolished the improvement of overall survival by systematic lymphadenectomy in all groups. Thus, lymphadenectomy did not improve recurrence-free survival in the intermediate risk or the high-risk group of patients CONCLUSIONS: Systematic pelvic and para-aortic lymphadenectomy did not improve the survival of patients with early stage I and II endometrioid endometrial cancer at intermediate and high risk of recurrence.

Association between endometriosis and gynecological cancers: a critical review of the literature

Endometriosis is one of the most common benign gynecological diseases with an occurrence approximately 10% in reproductive age. Endometriosis has been proposed as a possible precursor of certain ovarian carcinomas such as clear cell and endometrioid ovarian carcinomas. In addition to this pathogenic link, the association with other gynecological tumors and breast cancer has been studied on an epidemiological basis in several studies. The aim of this review was to critically present the recent published evidence on the association of endometriosis with gynecological cancer, and with a special emphasis on ovarian cancer. A search for eligible studies was conducted in three electronic databases, MEDLINE, EMBASE and CINAHL, for original research in humans published in any language. The present review includes studies examining the association between endometriosis and different types of gynecological cancer (i.e., 25 studies on ovarian cancer, 8 studies on breast cancer, 8 studies on endometrial cancer and 2 studies on cervical cancer). The present literature supports the pre-existing evidence suggesting an association between ovarian cancer and endometriosis and specifically its two histologic subtypes (endometrioid and ovarian clear cell cancer). The most recent population-based epidemiological studies cannot provide a clear association between endometriosis and endometrial, cervical or breast cancer.

Factors predicting recurrence in patients with stage IA endometrioid endometrial cancer: what is the importance of LVSI?

The aim of this study is to define the clinical and pathological prognostic factors for recurrence and to evaluate the recurrence patterns and adjuvant therapies used in this group of patients with stage IA endometrioid type endometrial cancer (FIGO 2009-International Federation of Gynecology and Obstetrics). Among the patients with epithelial endometrial cancer operated between January 1993 and May 2013 in a single institution, 720 patients with stage IA endometrioid endometrial cancer were included. Patients with a tumor type of serous, clear cell, mucinous, undifferentiated, and mixed type and with a tumor containing sarcomatous component and the patients with a secondary primer cancer were excluded from the study. Lympho-vascular space invasion (LVSI) was present in 60 (8.3%) patients. Pelvic and para-aortic lymphadenectomy was performed in 266 (36.9%) patients. Median follow-up time was 48 months (range 3-240). Recurrence occurred in 23 (3.4%) patients and 6 (0.9%) died of disease. The median time-to recurrence (TTR) was 24 months (range 4-52 months) in the patients with recurrence. LVSI was associated with recurrence in the univariate analysis. Five-year disease-free survival (DFS) decreased from 96.8 to 80.1% in the presence of LVSI (p < 0.001). This association could not be shown in patients who had had lymphadenectomy (p = 0.136). Extra-pelvic recurrence occurred in 6.7% and 1% of the patients with and without LVSI, respectively, (p = 0.001). Any independent prognostic factor could not be detected in the multivariate analysis. Only LVSI and tumor grade were associated with DFS and disease-specific survival (DSS), respectively, in the 686 patients with stage IA endometrial cancer in the univariate analysis, since these associations could not be shown in multivariate analysis.

Risk of postmenopausal hormone therapy and patient history factors for the survival rate in women with endometrial carcinoma

Postmenopausal hormone therapy (HT) is known to affect the development of hormone-dependent endometrial carcinoma (type I EC). Several studies on breast and ovarian carcinoma have shown that HT influences the molecular profile and prognostic behavior of these tumors. This study aimed to investigate the influence of prior HT and other risk factors on the prognosis in a cohort of patients with invasive endometrial carcinoma (EC). Among 525 patients diagnosed with EC between 1987 and 2010, 426 postmenopausal patients were identified. Information regarding HT was available in 287 of these patients, 78 of whom had a history of HT and 209 of whom did not. Both overall survival (OS) and progression-free survival (PFS) were analyzed. In addition to OS and PFS, risk factors such as age at diagnosis, postmenopausal HT, body mass index (BMI), diabetes mellitus, tumor stage, EC type (I or II), and recurrences were analyzed. Relative to HT alone, women with EC and a history of HT had a longer survival than those with no HT. However, the Cox proportional hazards model showed that it was not HT itself, but rather other characteristics in the HT group that were causally associated with longer survival. Age (the older, the worse) and tumor stage (the higher, the worse) were significant influences on overall survival. Patients with HT also had lower BMIs, less diabetes, more type I EC, and fewer recurrences in comparison with the non-HT group. With regard to the PFS, it made no difference whether the patient was receiving HT.

Minimally invasive surgery does not impair overall survival in stage IIIC endometrial cancer patients

We aimed to evaluate weather survival is impaired in stage IIIC endometrial cancer patients treated with minimally invasive surgery as compared to laparotomy. We analyzed surgical data and oncologic outcome of histologically proven stage IIIC endometrial cancer patients who were treated at our institution via laparotomy or via laparoscopic surgery. All the patients underwent a systematic pelvic and para-aortic lymphadenectomy and a complete tumor resection. Perioperative morbidity and overall survival of the patients subjected to the two surgical approaches were compared. Sixty-six patients with stage IIIC endometrial cancer were identified. Of these, 15 patients were operated via laparotomy and 51 via laparoscopy. The two groups were similar with regards to median age at diagnosis, BMI, histotype, number of affected lymph nodes, and median maximal diameter of the affected lymph nodes. Patients undergoing laparoscopic surgery had fewer perioperative complications, a smaller estimated blood loss, and were subjected less frequently to transfusions. Overall survival at 60 months of follow-up did not differ between the two groups. At uni- and multivariate analysis, surgical approach did not affect survival. Only age was a variable associated with overall survival. Minimally invasive surgery has better perioperative outcomes and does not impair survival in stage IIIC endometrial cancer patients. Age at diagnosis is the only factor independently affecting survival.

Adenomyosis as a prognostic factor in ovarian cancer: a retrospective study

Abstract Background Adenomyosis is a gynecological condition that frequently coexists with gynecological malignancies and has been shown to influence disease outcomes. However, its impact on ovarian cancer prognosis remains unclear. This study aimed to investigate the relationship between adenomyosis and clinicopathological and prognostic features in ovarian cancer patients. Methods We retrospectively analyzed 226 patients with ovarian cancer who underwent surgery between 2020 and 2023. The patients were divided into two groups based on the presence (n = 114) or absence (n = 112) of adenomyosis, confirmed by histopathological examination. Clinicopathological characteristics, including histological subtypes, disease-free survival (DFS), and overall survival (OS) were compared between the groups with a median follow-up of 36 months. Results Patients with adenomyosis demonstrated more favorable characteristics, including early stage disease (54.3% vs 39.2%, p = 0.048), lower-grade tumors (55.2% vs 31.2%, p = 0.049), and smaller tumor sizes (39.4% vs 26.7%, p = 0.043). Adenomyosis was significantly associated with endometrioid subtype (OR = 2.89, p = 0.043) and negatively associated with serous carcinoma (OR = 0.39, p = 0.034). Three-year DFS was significantly better in the adenomyosis group (79.2% vs 73.9%, p = 0.01), particularly in high-grade tumors (80% vs 58%, p &lt; 0.05). No significant difference was observed in overall OS (73.3% vs 73.1%, p = 0.14), although high-grade tumors with adenomyosis showed improved OS (71% vs 57%, p &lt; 0.05). Conclusion The presence of adenomyosis in patients with ovarian cancer was associated with favorable clinicopathological features, particularly endometrioid histology and low-grade tumors, and improved survival in high-grade tumors. These findings suggest a potential biological interaction between adenomyosis and ovarian cancer that warrants further investigation for personalized treatment approaches.

Impact of HIV infection on cervical intraepithelial neoplasia detection in pregnant and non-pregnant women in Germany: a cross-sectional study

Abstract Purpose Women living with HIV (WLWH) are frequently affected by cervical dysplasia caused by Human Papillomavirus (HPV) and invasive cervical cancer (CxCa). CxCa screening programs can include colposcopy, cytology, and HPV testing. These methods, however, have limitations in effectively stratifying cervical dysplasia. This study aimed to evaluate the applicability of an innovative mRNA-based multiplexed expression-quantifying assay in the detection and assessment of cervical dysplasia in WLWH. Methods The QuantiGene-Molecular-Profiling-Histology Assay (QG-MPH) was used to detect and quantify HPV oncogene and cellular biomarker mRNA expression. These results were included in the Risk Score (QG-MPH RS) calculations that inform about the presence and severity of dysplasia. QG-MPH RS results were compared to the highly sensitive Multiplexed Papillomavirus Genotyping (MPG) Assay and clinical results obtained by cytology, colposcopy and histology. For a standardized nomenclature of clinical results, the clinical ASSIST Score was used. Results Of 241 WLWH, including 96 pregnant women, a concordance between the QG-MPH RS and the ASSIST Score was found to 36.3% (49/135) in non-pregnant WLWH and 67.1% (57/85) in pregnant WLWH. The QG-MPH method demonstrated high specificity for detecting high-risk HPV (HR-HPV) genotypes and high-grade cervical dysplasia, achieving 89.6% and 82.4%, respectively, including pregnant and non-pregnant WLWH. Conclusion The QG-MPH assay shows potential for improving the detection and management of HPV-related cervical dysplasia in WLWH, including pregnant women. Its high specificity, however, is tempered by its tendency to overestimate dysplasia severity in certain cases, indicating that further research is needed to refine its use as a reliable diagnostic tool for this high-risk population.

Colposcopic findings to study cervical changes in reproductive age group women using various contraceptives

Colposcopy has a key role to play in see-and-treat programs for premalignant cervical lesions. The aim of the study/was to observe cervical changes with a colposcope using the Swede scoring system in fertile age group women using various contraceptives: conventional methods (barrier methods, coitus interruptus), oral contraceptives (OCPs), copper-T and bilateral tubectomy. The aim of the study was to observe and evaluate the colposcopic findings using the Swede scoring system for the diagnosis of premalignant/malignant lesions in reproductive age group women using various contraceptives. This was a prospective observational study, conducted among 200 women of reproductive age group using various contraceptives in a tertiary care institute in North India. PAP smear, direct visual examination, VIA (Visual Inspection with Acetic Acid) examination, colposcopic examination, and (biopsy if indicated) were done. The data were collected, and analysis was done using Microsoft Excel Office Software 2019 version 19.11 and epi info (CDC Atlanta) 7.23.1. Statistical analysis was done using percentages, mean, mode, median, standard deviation, Chi-square, Fisher's Test, and Anova Test. We found positive PAP (Papanicolaou test) smears in 61.50%, positive VIA examination in 9%, and positive findings in colposcopic examination in 28.50%, Swede score of 0-3 in 100% (0-91%, 1-2%, 2-6%, and 3-1%) and positive biopsy in 9% subjects. Malignant findings were observed in 1.00% of PAP smears. Colposcopic findings were CIN 1 (cervical intraepithelial neoplasia 1) in 8.5% and CIN 2 in 0.5% subjects. Swede score was zero in 91%, 1 in 2%, 2 in 6%, and 3 in 1% of subjects. HPE (histopathological examination) was chronic cervicitis in 8.50% and mild dysplasia/CIN 1 in 0.5%. No significant statistical associations between contraceptive choice and false-positive test results or disease prevalence was found in any group except Cu-T users p = 0.0184 (especially for CIN 2; p = 0.0109 and CIN 1 more in all groups than Cu-T users). Colposcopy had sensitivity 100%, specificity 91.46% (0/0 = 0%) PPV = 5.56%, NPV = 100%, Accuracy = 91.5% for detecting mild dysplasia/CIN-non-significant (p = 0.055). Our study had mainly low-grade lesions with 100% NPV. With increase in Swede Score, sensitivity increases but at the expense of specificity but it was statistically non-significant (p = 0.055). Our study may guide the rational use of colposcopy with Swede scoring for see-and-treat lesions, which is easy and with a low learning curve, as a tool for diagnosis but only in cases where indicated like unhealthy cervix because of the high rate of false-positive results. In low-grade lesions, it is highly useful to rule out the disease.

Characteristics and prognosis of borderline ovarian tumors in pre and postmenopausal patients

To compare patient characteristics, imaging results, surgical management and prognosis of borderline ovarian tumors (BOT) between pre and postmenopausal patients. A retrospective cohort of all cases of histologically verified BOT between 1990-2018, comparing presentation, imaging, surgical procedures and recurrence. Patients were included in the postmenopausal group if they reported 12 months of amenorrhea with or without menopausal symptoms. During this 28 year study period, 66 operations were performed in which BOT was confirmed. Postmenopausal patients were 37-89 years old and premenopausal patients 18-50 years old, with an average age of 63.9 ± 13.4 and 36.2 ± 8.4 years, respectively (p < 0.001). The majority of patients in both groups were diagnosed due to abdominal pain, followed by incidental diagnosis on routine ultrasound. Imaging and CA-125 levels upon presentation were similar. Almost sixty percent of postmenopausal and 26.3% of premenopausal patients underwent laparotomy (p = 0.01), while those who underwent laparoscopy were 35.7% and 60.5%, respectively (p = 0.03). Most postmenopausal patients underwent bilateral salpingo-oophorectomy (BSO), whereas premenopausal surgeries involved cystectomy. Nearly all study patients were diagnosed in stage one. Malignant transformation occurred in 7.1% of postmenopausal patients. No malignant transformation was found in premenopausal patients. BOT's present similarly in pre and postmenopausal patients. Postmenopausal patients undergo more extensive surgery, and are diagnosed in early stage disease. Despite a tendency for a more conservative approach in premenopausal patients, prognosis is similar in both groups.

Association between p16/Ki-67 dual stain cytology results prior to and 6 months after LLETZ treatment for CIN and the follow-up regimen three years after treatment: a retrospective cohort study

Investigate the association between p16/Ki-67 dual stain cytology test (DST) results, obtained prior to- and 6 months after LLETZ surgery for treatment of CIN, and the follow-up regimen three years after treatment. Secondary analysis of a prospective cohort study. Cervical cytology samples were obtained just prior to- and 6 months after LLETZ and underwent conventional liquid-based cytology (LBC) and p16/Ki-67 dual staining, as well as high-risk HPV genotyping. Clinical management after the LLETZ was according to Belgian national guidelines, with clinicians being blinded to DST results at both time points. Case records were reviewed in 01/2023 to document the follow-up regimen on average three years afterwards: women had either been advised to return to routine screening (i.e., three-annual LBC testing according to the Belgian guideline at that time), or were still subject to more frequent posttreatment surveillance (i.e., more frequent visits because of persistent hrHPV infection or absence of cytological regression). The follow-up regimen was recorded in 79/110 women originally recruited (72%). The need for continued intense posttreatment surveillance was associated with hrHPV infection 6 months after treatment (79.3% vs. 18.0%, p < 0.001), a positive DST result at baseline and follow-up (41.4% vs. 84.0%, p < 0.001-55.2% vs. 16.0%, p < 0.001), and persistent cytological anomalies at 6 months (at an ASCUS or worse threshold, 37.9% vs. 16.0%, p = 0.028). In multivariable logistic regression analysis, a positive DST at baseline (aOR 20.1, 95%CI 2.03-199.1) was independently associated with the need for intense post-treatment surveillance multiple years after treatment. This exploratory study suggests a possible role of dual-stain cytology in predicting treatment outcome multiple years after LLETZ surgery.

A retrospective study on the effect of surgical approaches and uterine manipulators on the prognosis of cervical cancer

Cervical cancer is a common gynecological malignancy. However, the optimal surgical approach and benefits of uterine manipulator use remain unclear in this context. This study aimed to compare patient outcomes among different surgical approaches including laparoscopic, combined vaginal and laparoscopic, abdominal, and robotic using the da Vinci surgical system. Moreover, we also aimed to examine the impact of uterine manipulator use in radical hysterectomy on the outcomes of patients with cervical cancer. This retrospective study included data from 848 patients with cervical cancer stage IA2-IIA2 that underwent a radical hysterectomy and pelvic lymphadenectomy at the Chinese PLA General Hospital between 2009 and 2019. Patient demographic and clinical characteristics, perioperative findings, and postoperative outcomes were examined. Patient characteristics, including body mass index, age, FIGO stage, pathological type, and tumor differentiation status and size, were comparable. Five-year survival rates were comparable among the groups that underwent different types of surgery regardless of disease stage. Five-year survival rates were comparable between the groups that underwent surgery with and without the use of a uterine manipulator. All surgical approaches examined in this study had comparable efficacy and safety profiles. The use of uterine manipulators during radical hysterectomy for cervical cancer does not increase the risk of death.

The characteristics of a fibroid in pregnancy can influence the perinatal outcome

The prevalence of fibroids during reproductive age is 20-25%. The presence of fibroids during pregnancy can impact perinatal outcomes. To determine whether fibroids affect perinatal outcomes and whether women who undergo fibroid surgery before pregnancy have better perinatal outcomes than those who have fibroids during pregnancy. The study also analyzes the optimal time interval between myomectomy and pregnancy and the characteristics of fibroids during pregnancy that affect perinatal outcomes. In both groups, fibroids' size, number, and location were analyzed to determine their influence on perinatal outcomes. The perinatal outcome is determined by gestational age, birth weight, Apgar score, intrauterine growth retardation, placental complications, and delivery method. A study was conducted on the perinatal outcomes of 338 women who had uterine fibroids during pregnancy and those who had undergone fibroid surgery before pregnancy. The medical records of women who gave birth at a tertiary university hospital were analyzed in this retrospective study. Women with submucosal fibroids have a lower gestational age of delivery (P = 0.0371), and those who operated on a higher number of fibroids before pregnancy had newborns with lower birth weights (P < 0.0001). Submucosal fibroids during pregnancy increase the chances of cesarean delivery (P = 0.0354). 14% of newborns have an Apgar score of less than seven within the first minute of birth in fibroids larger than 7 cm (P < 0.0001). There is a statistically significant difference in the perinatal outcome of newborns depending on the number, size and placement of uterine fibroids in both observed groups.

Novel predictors for identifying cervical minimal deviation adenocarcinoma patients with poor prognosis: a long-term observational study in a tertiary centre

To elucidate the clinicopathological features and prognostic factors of minimal deviation adenocarcinoma (MDA) of the uterine cervix, a clinically rare but highly invasive disease. This was a retrospective, observational, real-world study of 43 patients with pathologically confirmed MDA at the Obstetrics and Gynaecology Hospital of Fudan University between November 2010 and November 2021. Baseline clinicopathological data were collected and reviewed. Prognostic factors for progression-free survival (PFS) and overall survival (OS) were investigated by univariate and multivariate Cox proportional hazards analyses. Chief complaints included irregular vaginal discharge and/or bleeding (74.4%). Preoperative diagnosis was difficult, the detection rate was low (36.8%), all cases showed endophytic lesions, and 88.4% had deep stromal invasion, with biologically aggressive characteristics. The ovarian metastasis rate was high (16.3%, 7/43). The median maximum diameter of the tumour (MDOT) was 4.3 cm (range, 0.5-8.0 cm). MDOT was significantly associated with OS (P = 0.009), and the optimal cut-off value to define bulky MDA was 5.5 cm (P < 0.0001, χ= 21.161) using X-tile software. Independent prognostic factors included MDOT (HR = 10.095, P = 0.001) and ovarian metastasis (HR = 5.888, P = 0.008) for OS and MDOT (HR = 3.944, P = 0.028), ovarian metastasis (HR = 9.285, P = 0.001), and deep infiltration (HR = 3.627, P = 0.048) for PFS. Endophytic lesion development and ovarian metastasis are likely in MDA. A bulky tumour and ovarian metastasis indicate a worse prognosis. Given the special biological features of MDA, it is more appropriate to use 5.5 cm as the threshold for defining a bulky tumour than it is to use 4 cm. Ovary removal should be given higher priority to improve prognosis.

Prognostic value of FDG-PET SUV changes in cervical cancer following radiation therapy: a retrospective cohort study

Abstract Purpose This study sought to determine the relationship between cervical cancer recurrence and post-treatment change in standardized uptake value (SUV) of 18F-2-fluoro-2-deoxy-D-glucose-positron emission tomography (FDG-PET) in the cervix and lymph nodes. Methods This retrospective cohort study included patients who received curative intent radiation therapy for biopsy-proven stage I–IVA locally advanced cervical cancer at a single tertiary referral center from 2009 to 2021. The exposure was percent change in SUV from pre- to post-treatment FDG-PET scans at the cervix and lymph nodes. The primary outcome was recurrence rate, and secondary outcomes were overall and progression-free survival. Firth’s penalized logistic regression and Cox proportional hazards models were used to assess associations. Results 55 patients met eligibility criteria. Recurrence rate was 27% (15/55); of these, 33% had local recurrence (5/55) and 67% had distant recurrence (10/55). Median percent decrease of cervical SUV after treatment in those with and without recurrence was similar (71.4 vs 68.8, p  = 0.89); this remained consistent when analyzing those with local recurrence only (70.5, p  = 0.95). When the percent decrease in cervical SUV was examined in intervals (&lt; 25%, 25–50%, 50–75%, &gt; 75%), this was also not predictive of local ( p  = 0.91) or overall ( p  = 0.75) recurrence. Median percent decrease at the most avid and distant lymph node in those with and without recurrence was not significantly different ( p  &gt; 0.05). Neither change in cervical nor lymph node SUV was associated with overall or progression-free survival. Conclusion Changes in SUV after treatment may not be a reliable stand-alone marker for predicting recurrence or survival in locally advanced cervical cancer after treatment with radiation therapy.

Endocervical crypt involvement by high-grade cervical intraepithelial neoplasia and its association with high-grade histopathological recurrence after cervical excision in women with negative excision margins: a systematic review and meta-analysis

Abstract Background There is a growing body of evidence suggesting that endocervical crypt involvement by high-grade cervical intraepithelial neoplasia (CIN) may represent a risk factor for disease recurrence after cervical treatment. Objectives To provide a systematic review and meta-analysis on whether endocervical crypt involvement by high-grade CIN on the excised cervical specimen is associated with high-grade histopathological recurrence during the follow-up of women after cervical excisional treatment. Search strategy We searched the Medline, Scopus, Central, and Clinical Trials.gov databases from inception till May 2023. Selection criteria Studies that reported on women with a single cervical treatment with any method of excision for CIN2 or CIN3 lesion, negative excision margins, and whose recurrence was defined histopathologically were included. Data collection and analysis Two reviewers independently evaluated study eligibility. We used the fixed effects model for meta-analysis. Main results There were 4 eligible studies included in the present systematic review that evaluated 1088 women treated with either large loop excision of the transformation zone (LLETZ) or with cold knife conization (CKC). We found no significant association of endocervical crypt involvement by CIN2-3 with high-grade histopathological recurrence at follow-up after cervical excision (OR 1.93; 95% CI 0.51–3.35). The subgroup analysis of women with LLETZ cervical excision showed again no significant association with high-grade histopathological recurrence at follow-up (OR 2.00; 95% CI 0.26–3.74). Conclusion Endocervical crypt involvement by high-grade CIN does not seem to be a risk factor for high-grade histopathological recurrence after cervical excision with negative excision margins.

Status and related factors of postoperative recurrence of ovarian endometriosis: a cross-sectional study of 874 cases

Abstract Purpose Exploring the status and related factors of postoperative recurrence of ovarian endometriosis. Methods This study analyzed the results of questionnaires conducted in 27 hospitals across the country from January 2019 to November 2021. All women were divided into recurrence group and non-recurrence group to analyze the recurrence rate and related factors after ovarian endometriosis surgery. Results The recurrence rates of ovarian endometriosis within 1 year, 1–2 years, 2–3 years, 3–4 years, 4–5 years and more than 5 years were 6.27%, 35.85%, 55.38%, 65.00% and 56.82%, respectively. Significant differences were found between two groups in terms of age at surgery (OR: 0.342, 95%CI: 0.244–0.481, P &lt; 0.001), presence of dysmenorrhea (OR: 1.758, 95%CI: 1.337–2.312, P &lt; 0.001), presence of adenomyosis (OR: 1.948, 95%CI: 1.417–2.678, P &lt; 0.001) and family history of endometriosis or adenomyosis (OR: 1.678, 95%CI: 1.035–2.721, P = 0.021). The age at surgery (OR: 0.358, 95%CI: 0.253–0.506, P &lt; 0.001), presence of dysmenorrhea (OR: 1.379, 95%CI: 1.026–1.853, P = 0.033) and presence of adenomyosis (OR: 1.799, 95%CI: 1.275–2.537, P = 0.001) were significantly associated with endometrioma recurrence in multivariate analysis. No significant associations were found between the recurrence rate and body mass index (BMI), educational background, age of menarche, gravida, parity, uterine leiomyoma, endometrial polyps or postoperative use of gonadotropin-releasing hormone agonist (GnRH-a). Conclusions Dysmenorrhea and presence of adenomyosis are independent risk factors for postoperative recurrence of ovarian endometriosis, and older age is an independent protective factor for postoperative recurrence.

Ovarian teratoma-associated anti-NMDAR encephalitis: a single-institute series of six patients from China

Abstract Purpose Ovarian teratoma-associated anti-N-methyl-d-aspartate receptor encephalitis is a rare disease with uncertain etiology and pathogenesis. The disorder is severe and rare with a great impact on young adults. This study aimed to improve the awareness of the disease from experience in our single center. Methods Between July 2012 and December 2019, six patients with ovarian teratoma-associated anti-N-methyl-d-aspartate receptor encephalitis were enrolled in Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University. All patients’ data like manifestations, laboratory and radiological data, treatment, and follow-up were reviewed. Results Typical psychotic symptoms, memory, and consciousness disorders accompanied by seizures were observed in all patients from this study. All six patients showed positive signals in serum and cerebrospinal fluid samples for N-methyl-d-aspartate receptor and received immunotherapy. Three patients underwent unilateral oophorocystectomy and the other three underwent unilateral oophorectomy through minimally invasive surgeries, including laparoscopic and single-port laparoscopic surgeries. The median follow-up time 24.5 months (range from 6 to 93 months). No death occurred. Two patients had recurrent psychotic symptoms while the left four patients had no mental symptoms or tumor recurrence during postoperative follow-up. Conclusions For patients with clinical manifestations of unexplained acute psychiatric symptoms accompanied by seizures, memory, and consciousness disorders, the possibility of anti-N-methyl-d-aspartate receptor encephalitis should be considered. To confirm the diagnosis, examinations of anti-N-methyl-d-aspartate receptor antibodies need to be completed as early as possible. Immunotherapy and tumor location should be given in time once the diagnosis is defined. We recommended removing the tumor as soon as possible without concerning whether the patient is in the acute phase or not. The surgical procedure should be decided based on pathology, age, fertility desire, and patients’ requirements and it should be ensured that tumors are completely removed during operation. Postoperative follow-up is particularly important.

TP53 germline mutations in the context of families with hereditary breast and ovarian cancer: a clinical challenge

Abstract Purpose TP53germline (g) mutations, associated with the Li-Fraumeni syndrome (LFS), have rarely been reported in the context of hereditary breast and ovarian cancer (HBOC). The prevalence and cancer risks in this target group are unknown and counseling remains challenging. Notably an extensive high-risk surveillance program is implemented, which evokes substantial psychological discomfort. Emphasizing the lack of consensus about clinical implications, we aim to further characterize TP53g mutations in HBOC families. Methods Next-generation sequencing was conducted on 1876 breast cancer (BC) patients who fulfilled the inclusion criteria for HBOC. Results (Likely) pathogenic variants in TP53 gene were present in 0.6% of the BC cohort with higher occurrence in early onset BC &lt; 36 years. (1.1%) and bilateral vs. unilateral BC (1.1% vs. 0.3%). Two out of eleven patients with a (likely) pathogenic TP53g variant (c.542G &gt; A; c.375G &gt; A) did not comply with classic LFS/Chompret criteria. Albeit located in the DNA-binding domain of the p53-protein and therefore revealing no difference to LFS-related variants, they only displayed a medium transactivity reduction constituting a retainment of wildtype-like anti-proliferative functionality. Conclusion Among our cohort of HBOC families, we were able to describe a clinical subgroup, which is distinct from the classic LFS-families. Strikingly, two families did not adhere to the LFS criteria, and functional analysis revealed a reduced impact on TP53 activity, which may suit to the attenuated phenotype. This is an approach that could be useful in developing individualized screening efforts for TP53g mutation carrier in HBOC families. Due to the low incidence, national/international cooperation is necessary to further explore clinical implications. This might allow providing directions for clinical recommendations in the future.

Use of fertility treatments in BRCA1/2 mutation carriers and risk for ovarian and breast cancer: a systematic review

Abstract Purpose Mutations in the genes BRCA1 and BRCA2 represent a significant risk factor for ovarian and breast cancer. With increasing number and success rates, fertility protection and treatment are gaining importance also for BRCA1/2 mutation carriers. However, the effect on primary cancer risk and risk for recurrence remains unclear. This review analyses the published data on fertility treatment and risk of ovarian and breast cancer in BRCA1/2 mutation carriers. Methods In this review, we included all relevant articles published in English from 1995 to 2018. Literature was identified through a search on PubMed and Cochrane Library. Results We identified one retrospective cohort and one case–control study regarding the association of fertility treatments and ovarian cancer risk in BRCA mutation carriers. The studies show no increase in ovarian cancer risk. Furthermore, one case–control study on the association between fertility treatment and breast cancer risk in BRCA mutation carriers and one prospective cohort study on the long-term safety of medication used for fertility preservation in women with a history of breast cancer were identified. One of the studies shows a possible adverse effect for gonadotropin-containing medication. Conclusion Possible increases in cancer risk associated with fertility treatments in BRCA1/2 mutation carriers cannot be excluded at this time. Based on the existing studies, BRCA1/2 mutation carriers should not be generally excluded from fertility treatments. However, they have to be informed about limited data and possible increases in cancer risk.

Use of oral contraceptives in BRCA mutation carriers and risk for ovarian and breast cancer: a systematic review

Abstract Purpose BRCA mutation carriers have an increased risk of developing breast or ovarian cancer. Oral contraception (OC) is known to increase breast cancer and reduce ovarian cancer risk in the general population. This review analyses the published data on OC and risk of cancer in BRCA mutation carriers. Methods We included all relevant articles published in English from 1995 to 2018. Literature was identified through a search on PubMed and Cochrane Library. Results We included four meta-analyses, one review, one case–control study and one retrospective cohort study on the association between ovarian cancer and OC in BRCA mutation carriers. All report a risk reduction for the OC users and several also describe an inverse correlation with duration of use. Regarding breast cancer, we included four meta-analyses, one review, one case–control study, two case-only studies, one prospective and one retrospective cohort study. Some studies report a risk elevation, while others did not find an association between OC use and breast cancer in BRCA mutation carriers. In other studies, the association was limited to early-onset breast cancer and/or associated with young age at first start of OC. Conclusion Oral contraception leads to a risk reduction of ovarian cancer also in BRCA mutation carriers. An increase in breast cancer risk due to OC cannot be excluded. Women with BRCA mutation who consider OC use have to be informed about possible increase in breast cancer risk and alternative contraceptive methods. OC should not be used for the prevention of ovarian cancer in this population.

Healthy lifestyle behaviors and gynecological cancer awareness in women academicians: a descriptive and correlational study

Abstract Objective To determine the healthy lifestyle behaviors (HLBs) and gynecological cancer awareness (GCA) levels of women academicians and to investigate the correlation between HLBs and GCA. Methods A descriptive correlational study design was used to determine the healthy life behaviors and gynecological cancer awareness levels of women academicians and to investigate the correlation between them. A total of 353 women academicians were included between 1st March 2020 and 1st January 2021. The data were collected using Introductory Form, Health Promoting Lifestyle Profile II, and Gynecological Cancer Awareness Scale. Results The women’s healthy life behaviors levels were close to moderate and gynecological cancer awareness levels were high. The median healthy life behaviors score was significantly higher in women who worked as an assistant professor, considered the age of menarche and menopause as risk factors for women cancers, consumed regular snacks, received information about GCs, and had regular pap-smears (p &lt; .05). The median gynecological cancer awareness score was significantly higher in women who worked as an assistant professor, considered the age of menarche and menopause as risk factors for women cancers, received information about GCs, and experienced pregnancy process (p &lt; .05). In addition, as women’s healthy life behaviors levels increased, their gynecological cancer awareness levels also increased. The healthy life behaviors score was positively and moderately associated with the gynecological cancer awareness score (p &lt; .05). Discussion Our findings highlight the potential to promote monitoring of women’s healthy lifestyle behaviors and gynecological cancer awareness in the community by planning effective interventions.

Lower extremity lymphedema in patients with gynecologic cancer: Validation of the Gynecologic Cancer Lymphedema Questionnaire (GCLQ) in German language and investigation of lymphedema real-world treatment

Abstract Purpose The Gynecologic Cancer Lymphedema Questionnaire (GCLQ) is an established patient-reported outcome measure for lower extremity lymphedema (LEL) in gynecologic oncology. We aimed to validate the GCLQ in German language (GCLQ-GER) for lymphedema detection in German-speaking patients and also investigated real-world patterns of lymphedema treatment. Methods The GCLQ was translated from English into German in accordance with the standards of a professional translation process. Subsequently, the questionnaire was administered in a prospective observational study including 102 patients who had undergone lymph node dissection (LND) within gynecologic cancer surgery. Various test quality criteria were calculated for the GCLQ-GER. As gold standard of testing methods, patients were clinically evaluated for LEL, and limb volume measurements were taken. Further data for lymphedema treatment were collected in patients with lymphedema diagnosis. Results Patients with LEL had increased GCLQ-GER total scores (mean 7.27) compared to patients without LEL (mean 1.81), p &lt; 0.001. High diagnostic accuracy was indicated by the large area under the receiver operating characteristics curve (AUC) of 0.874 (95% CI 0.802–0.946). Based on sensitivity and specificity values ≥ 79.0%, the GCLQ total score ≥ 4 was determined as the optimal cut-off value to identify LEL. Excellent internal consistency was demonstrated by Cronbach’s alpha of 0.876. The clinical examination revealed a LEL prevalence of 48.0% (n = 49), and 85.7% (n = 42) of these patients received treatment. Conclusion The GCLQ-GER is a valid and feasible patient-reported outcome measure for lymphedema detection in German-speaking gynecologic cancer survivors. Its clinical introduction could improve secondary prevention of lymphedema and real-world treatment.

Comparison of survival outcomes of neoadjuvant therapy and direct surgery in IB2/IIA2 cervical adenocarcinoma: a retrospective study

Abstract Purpose This retrospective study compared the efficacy and survival of patients with cervical adenocarcinoma (IB2/IIA2; FIGO2009) treated with neoadjuvant chemotherapy before radical surgery (NACT + RS), neoadjuvant chemoradiation therapy before radical surgery (NACRT + RS), or primary radical surgery (RS). Methods Between January 2008 and November 2015, 91 patients diagnosed with stage IB2/IIA2 cervical adenocarcinoma were enrolled, including 29 patients who received RS, 24 patients who received NACT + RS, and 38 patients who received NACRT + RS. Results The characteristics of patients were balanced among the three groups, and the median follow-up time was 72 months. The 5 year disease-free survival (DFS) rate was 75.8% and the 5 year overall survival (OS) rate was 85.0%. Univariate analysis revealed that effectiveness of neoadjuvant treatment, tumor size, lymph node metastases, and depth of stromal invasion were the factors predicting recurrence and mortality. Multivariate Cox proportional analysis revealed that the occurrence of a lymph node metastasis was an independent prognostic factor of DFS (hazard ratio [HR] = 0.223; 95% confidence interval [CI]: 0.060–0.827) and OS (HR = 0.088; 95% CI: 0.017–0.470). On survival analysis of preoperative adjuvant chemotherapy and primary surgery, the 5 year OS (P = 0.010) and DFS (P = 0.016) rates for the NACRT + RS group were significantly lower than those for the RS group. Conclusion Stage IB2/IIA2 cervical adenocarcinoma patients who received primary RS had a better DFS and OS than those who received preoperative NACRT. There was no significant difference when compared to the preoperative NACT group.

Safety of indocyanine green for lymph node mapping in early-stage vulvar cancer: multicenter evaluation and systematic review

Abstract Purpose This study aimed to evaluate the rate and severity of allergic events associated with the use of indocyanine green (ICG) in sentinel lymph node biopsy (SLNB) for patients with early-stage vulvar cancer. The research question focused on whether ICG administration poses a significant risk of allergic reactions, especially in patients with a history of allergies to iodinated contrast. Methods We conducted a retrospective study after prospective multicenter recruitment endorsed by the Spanish Investigational Network Gynecologic Oncology Group. Data on patient demographics, history of allergic reactions, and ICG administration were collected. A systematic literature review was performed to assess existing studies on ICG-related allergic reactions in SLNB. Results Among the 75 patients, 66 (75%) have been exposed to iodinated contrasts and 2 (3%) had a documented iodinated contrast allergy with a mild reaction. There were no intraoperative complications. During the postoperative period, there were only minor complications (15 (20.0%) grade I and 13 (17.3%) grade II of Clavien–Dindo classification), and none associated with the injection of ICG or allergen-based that could be related. The systematic review of 11 studies involved 206 patients and 354 groins. The history of allergy to iodinated contrast was not recorded in any of them. We observed no patients with adverse reactions related to this tracer after peritumoral injection. Conclusion Our findings suggest that peritumoral ICG injection for SLNB in early-stage vulvar cancer could be safe. This study reinforces the potential for ICG to be a reliable tracer in vulvar cancer staging.

Influence of resection distance on vulvar cancer relapse: a retrospective analysis

Abstract Objective This study evaluates the effect of resection margin distance on disease-free survival (DFS) and (local) recurrence rates in patients with vulvar squamous cell carcinoma (SCC) while assessing the impact of associated factors such as lichen sclerosus (LS) and lymph node metastasis. Methods A retrospective single-center analysis was conducted on 150 patients treated for vulvar SCC between 2004 and 2014 at University Hospital Düsseldorf. Univariate and multivariate regression analyses were performed to evaluate the impact of clinical and pathological factors on DFS. Additionally, a literature review was conducted to summarize existing evidence on resection margins. Results The findings suggest that a resection margin exceeding 8 mm does not significantly improve DFS (HR 1.14, CI 1.01–1.28, p = 0.029). LS was significantly associated with recurrence (HR 2.36, CI 1.13–4.91, p = 0.02) and reduced DFS. Univariate analysis identified lymph node metastasis as a significant predictor of DFS; however, this association was not retained in multivariate analysis. Conclusion Although current guidelines advocate for resection margins &gt;8 mm, our findings suggest that smaller margins may be acceptable in selected patients, particularly those without LS and tumors located near critical structures (e.g., the anus, clitoris, or urethra). These considerations should inform personalized treatment strategies and follow-up care.

Robotic-assisted surgery in extremely obese patients: a multidisciplinary approach for a patient with a BMI of 101.7 kg/m2

Abstract Background The prevalence of obesity has risen significantly, affecting over 19% of the German population. Obesity is frequently associated with endometrial cancer, presenting considerable challenges in pre-, intra- and postoperative management. Challenges with intubation, patient positioning, respiratory and cardiac complications as well as wound dehiscence are commonly encountered in this patient population. Methods and results For patients with uterine cancer, surgical intervention is essential for staging, symptom control, and potential cure. Minimally invasive approaches, particularly robotic-assisted surgery, have expanded the possibilities for treating morbidly obese patients. Robotic systems facilitate navigation around anatomical barriers and reduce surgeon fatigue. However, despite the technological advancements, morbidly obese patients often face increased perioperative risks and prolonged postoperative recovery. Laparoscopic procedures in steep Trendelenburg position for morbidly obese patients pose unique challenges, particularly in anesthesiological management. These challenges necessitate individualized ventilatory and hemodynamic support to ensure patient safety. This case highlights a multidisciplinary approach to managing a patient with extreme obesity (BMI 101.7 kg/m 2 ) undergoing roboticassisted surgery for uterine cancer. It underscores the importance of comprehensive preoperative planning, intra-operative considerations, and post-operative care in minimizing complications and optimizing outcomes. Conclusion Our case exemplifies our experience from similar cases and demonstrates that robotic-assisted surgery for endometrial cancer in obese patients can represent a safe and feasible option, characterized by a low complication rate, minimal blood loss, and a short hospital stay.

Evolution of lymphovascular space invasion in early-stage endometrial carcinoma: stratification, quantification, and clinical implications: a systematic review

Endometrial carcinoma (EC) represents the most prevalent malignancy of the female genital tract in the United States, with lymphovascular space invasion (LVSI) recognized as a critical prognostic factor that significantly influences disease outcomes. This review aims to elucidate the evolving understanding of LVSI in early-stage EC, highlighting its implications for stratification, quantification, and clinical management. A systematic review was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Comprehensive searches of the PubMed, Web of Science, and Embase/MEDLINE databases were performed for studies published from January 1, 1985, to November 16, 2024. Peer-reviewed articles that reported multivariable hazard ratios (HR) for LVSI in endometrial cancer were included, while meta-analyses, reviews, and case reports were excluded from analysis. A total of 6 studies involving 2,345 patients were included. The majority of the population was characterized by endometrioid histotype (85.7%) and classified as FIGO stage I (75.1%). LVSI was documented in 21.5% of cases, with 62.4% of patients receiving adjuvant treatment. The literature on LVSI was categorized into three thematic areas: stratification classifications, quantitative assessments, and guideline development, illustrating the progression from binary systems to more nuanced tiered classifications that enhance prognostic accuracy. Foundational studies established LVSI as a significant risk factor in endometrial cancer, while subsequent research has refined its classification and quantification. However, inconsistencies in LVSI thresholds among current clinical guidelines pose challenges for standardization in practice. Addressing these discrepancies through future research, including multicenter studies and the integration of emerging technologies, is crucial for improving risk stratification and clinical management of endometrial carcinoma.

Prognostic and clinical heterogeneity of PD1 and PD-L1- immunohistochemical scores in endometrial cancers

Abstract Introduction PD1/PD-L1 inhibition (ICi) has recently become a new standard of care for patients with advanced MMR-deficient (MMRd) endometrial cancers. Nevertheless, response to immunotherapy is more complex than the presence of a single biomarker and therefore it remains challenging to predict patients response to ICi beyond MMRd tumors. Elevated PD-L1 expression (CPS ≥ 1) is often used as a prognostic marker as well as a predictive biomarker of response to ICi in different tumor types. In a retrospective, patient derived study, we analyzed PD1- and PD-L1 staining and correlated the results of different scores to clinical data to evaluate the prognostic impact of these scores. Materials and methods Immunohistochemical analysis of the receptor PD1 and the receptor ligand PD-L1 were performed on TMAs of primary paraffin‑embedded tumor samples. All patients were treated for primary endometrial cancer in the Department of Gynecology and Obstetrics, University Medical Center Schleswig–Holstein, Campus-Lübeck, Germany between the years 2006–2018. The evaluation and determination of the tumor proportion scoring (TPS), the combined positive score (CPS) and the immune cell scoring (IC) was automatically assessed semi-quantitatively, and results were correlated with clinicopathological characteristics and survival. Results 130 samples were evaluable and 64% showed a positivity (IC &gt; 0) for the receptor PD1 and 56% for the receptor ligand PD-L1. Patients with a PD1 IC Score ≥ 1 showed a significant longer disease-free survival of 140 months (95% confidence interval (CI): 124–158) compared to patients with a lower IC &lt; 1 for PD1 of 89 months (95% confidence interval (CI): 69–110); p = 0.017). Furthermore, the disease-free survival for patients with a CPS ≥ 5 for PD1 was longer (153.7 months (95% confidence interval (CI): 134–173.6) vs. 98.6 months (95% confidence interval (CI): 83–114); p = 0.036). Additionally, a PD1 CPS ≥ 5 showed a better overall survival but the result was not statistically significant. No difference in survival was found between patients with PD-L1 higher or lower than CPS 5. Conclusion In this study we pointed out that there are significant clinical differences among several immunohistochemical scoring systems. In our trial, a PD1-positivity with CPS ≥ 5 and IC ≥ 1 were significantly associated to a better disease-free survival while there was no association with TPS. The PD1-IC scoring was associated with MMRd while the TPS scoring was not. Therefore, PD1-IC could be more appropriate for endometrial carcinomas compared to TPS and could also add prognostic information beside the more established PD-L1-staining. Further prospective studies are needed for a validation of these scores in combination with other biomarkers.

Clinical relevance of circulating tumor cells in ovarian, fallopian tube and peritoneal cancer

Abstract Purpose Presence of circulating tumor cells (CTCs) is associated with impaired clinical outcome in several solid cancers. Limited data are available on the significance of CTCs in gynaecological malignancies. The aims of the present study were to evaluate the dynamics of CTCs in patients with ovarian, fallopian tube and peritoneal cancer during chemotherapy and to assess their clinical relevance. Methods 43 patients with ovarian, fallopian tube and peritoneal cancer were included into this prospective study. Patients received chemotherapy according to national guidelines. CTC analysis was performed using the CellSearch system prior to chemotherapy, after three and six cycles. Results In 26% of the patients, ≥ 1CTC per 7.5 ml of blood was detected at baseline (17% of patients with de novo disease, compared to 35% in recurrent patients). Presence of CTCs did not correlate with other factors. After three cycles of therapy, CTC positivity rate declined to 4.8%. After six cycles, no patient showed persistent CTCs. Patients with ≥ 1 CTC at baseline had significantly shorter overall survival and progression-free survival compared to CTC-negative patients (OS: median 3.1 months vs. not reached, p = 0.006, PFS: median 3.1 vs. 23.1 months, p = 0.005). When only the subgroup with newly diagnosed cancer was considered, the association between CTC status and survival was not significant (OS: mean 17.4 vs. 29.0 months, p = 0.192, PFS: 14.3 vs. 26.9 months, p = 0.085). Presence of ≥ 1 CTC after three cycles predicted shorter OS in the entire patient cohort (p &lt; 0.001). Conclusions Hematogenous tumor cell dissemination is a common phenomenon in ovarian, fallopian tube and peritoneal cancer. CTC status before start of systemic therapy correlates with clinical outcome. Chemotherapy leads to a rapid decline in CTC counts; further research is needed to evaluate the clinical value of CTC monitoring after therapy.

The prevalence and clinical relevance of cervical abnormalities after an amputation of the cervix as part of prolapse surgery: a cross-sectional study

Abstract Purpose To examine the safety of omitting routine histopathological examination by determining the prevalence of cervical pathology in women after cervical amputation as part of pelvic organ prolapse (POP) surgery without pre-existing indication for histology and the necessity of additional treatment. Methods A cross-sectional study was performed using data of women who underwent cervical amputation as part of POP without pre-existing indication for histopathological examination, obtained from Palga, the Dutch nationwide pathology databank, between January 1991 and January 2022. Main outcome measures The prevalences of the following histological diagnoses were determined: Cervical Intraepithelial Neoplasia (CIN I–III), adenocarcinomas in situ (AIS), cervical carcinomas, and other malignancies. Results In total, 14.887 patients were included in this study, with a median age of 61.4 years (SD = 11.7). The prevalence of CIN II+ lesions was 6.9 [95%-CI 5.6, 8.3] per 1000 women, while one cervical carcinoma (6.7 [95%-CI −0.6, 19.9] per 100.000 women) was reported (stage IA1 microinvasive squamous cell carcinoma). Conclusion This study found a prevalence of 0.7% for CIN II+ incidental findings in women undergoing amputation of the cervix as part of POP surgery. No additional treatments were required after the final histopathological results. The decision to omit routine histopathological examination could potentially be safe, offering the prospect of reduced healthcare costs and environmental impact. Healthcare professionals should individually assess the risks and benefits of omitting and/or replacing routine histopathological examination.

Management and natural course of CIN 1 and CIN 2 before and after implementation of the revised cervical cancer screening in Germany

In 2020, Germany implemented a revised cervical cancer screening program, incorporating co-testing with cytology and human papillomavirus (HPV) testing for women aged 35 and older. This study describes patient characteristics, referral patterns, and follow-up outcomes of histologically confirmed cervical intraepithelial neoplasia (CIN) 1 and CIN 2 lesions before and after the introduction of the organized cervical cancer screening program in Germany. In a hybrid prospective-retrospective study, we analyzed two consecutive cohorts of patients with histologically confirmed CIN 1 or CIN 2 at the Department of Women's Health, University Hospital Tuebingen, between 2013 and 2022. Patient characteristics, referral indications, and follow-up outcomes were described and compared. Patients post-2020 were older (median 41 vs. 31 years), more often hrHPV-positive (93.4% vs. 63.3%), and more frequently presented with CIN 1 (62% vs. 51%). Immediate intervention was less common post-2020 (CIN 1: 7% vs. 25%; CIN 2: 37% vs. 67%). Among those followed, remission was higher in the post-2020 cohort (CIN 1: 63.5% vs. 42.2%; CIN 2: 61.6% vs. 41.0%). Progression to CIN 3 remained rare in both cohorts. Multivariable regression indicated that CIN 2 diagnosis and smoking reduced remission, while the post-2020 period was associated with increased remission odds. The differences in remission and persistence between cohorts likely reflect changes in referral pathways, patient age rather than causal program effects. These data provide a descriptive benchmark for clinicians, supporting conservative management of CIN 1 and selected CIN 2 under the new screening program.

Preoperative relugolix combination therapy in laparoscopic myomectomy: a case series evaluating impact on surgical planes and operative outcomes

Gonadotropin-releasing hormone (GnRH) receptor antagonists in combination therapy offer a promising advancement in the medical management of uterine fibroids. While effective for symptom control, limited data exist on their impact on surgical outcomes, particularly during laparoscopic myomectomy. This case series describes the surgical findings in three patients who received preoperative Relugolix combination therapy (Relugolix-CT: relugolix-estradiol-norethisterone acetate) compared to no pretreatment. We conducted a retrospective review of 24 patients who underwent laparoscopic myomectomy over a 6-month period. Three patients received a preoperative course of Relugolix-CT for 3, 6, and 9 months, respectively, while 21 patients underwent surgery without pretreatment. Blood loss was lower in the Relugolix-CT group (216.6 mL ± 189.7) vs. the no-pretreatment group (354.8 mL ± 131.9. Operating time was similar (148.3 vs. 148.1 min), as was duration of inpatient stay (1.3 vs. 2.0 days). No complications occurred in either group. Notably, in all cases with Relugolix-CT pretreatment, no distortion or fibrosis of the fibroid pseudocapsule was noted, allowing for complete resection of the fibroids. This case series suggests that preoperative Relugolix-CT does not adversely affect surgical planes or operative outcomes. Although preliminary, these findings suggest benefits for surgical optimisation and support further investigation in larger, controlled studies.

The treatment of cervical intraepithelial neoplasia grade 2 (HSIL): between active surveillance and surgery—a 10-year monocentric data analysis

Abstract Purpose In recent years, active surveillance has been introduced as an alternative to excisional treatment in younger women with cervical intraepithelial neoplasia grade 2 (CIN 2) because spontaneous regression rate is high and excisional treatment is associated with an increased risk of preterm birth. However, the potential effect of this conservative approach on the risk of developing cervical cancer has not been evaluated very well. Methods The present study offers a real-life analysis of treatment pathways for patients diagnosed with CIN 2. Results Following CIN 2 diagnosis, 84 cases out of 187 (44.9%) were managed conservatively for at least 7 months and 103 cases (55.1%) were admitted for an excisional procedure LEEP (loop electrosurgical excision procedure). Out of 84 patients observed with a CIN 2 diagnosis, 64 showed persistence of CIN 2 lesion (76.2%), 14 showed spontaneous remission under active surveillance (16.7%), 4 progressed to CIN 3 (4.8%) and 2 to carcinoma (one case of vaginal carcinoma and one case of cervical adenocarcinoma (Supplementary Fig. 1) (2.4%). We observed the regression of CIN 2 in 16.7% of patients on active surveillance and this was statistically significant during the observation period (95% CI 5.72–10.85, p &lt; 0.001) (Supplementary Fig. 3). Conclusion The choice of treatment was strongly associated with HPV typing in our study. Patients with HPV 16 infection underwent surgery more often than patients without HPV 16 infection. The difference in our study was statistically significant (p &lt; 0.001). We observed regression of CIN 2 in 16.7% of patients on active surveillance and this was statistically significant to the observation period (95% CI 5.72–10.85, p &lt; 0.001).

At-home self-collection device offers an effective and preferred method to engage high BMI women in cervical cancer screening: method comparison study

Cervical cancer (CxCa) screening rates are lower among women with high BMI in the US, leading to increased prevalence and worse outcomes from cervical dysplasia and cancer in this group. The main barriers to participation in screening relate to the in-clinic speculum exam, which could be overcome with an at-home self-collect (SC) screening device optimized for differing body types. This prospective method comparison study recruited 609 screening-eligible participants aged 25 to 65 years, enrolled from November 20, 2023, to April 5, 2024. SC was performed by the participant in a simulated home environment, using a novel device optimized for differing body sizes. Eligible participants collected a vaginal sample with the SC device, followed immediately by a clinician-collection (CC) sample using a speculum and broom. The sample pairs were shipped to the lab, where the SC sample was eluted into PreservCyt and tested on an FDA-approved high-risk human papillomavirus (hrHPV) test approved for primary screening. Participants completed usability and preference surveys. Endpoints included the detection of hrHPV between SC and CC samples, as well as other study measures, such as clinical sensitivity for high-grade cervical dysplasia, usability, and preferences by BMI category. Five hundred ninety (590/599) participants had data available for this sub-analysis, based on body mass index (height and weight were recorded via self-report). Results and preferences of participants with a higher BMI (≥ 35) are highlighted herein. BMI ranged from 16 to 66 for the entire study group, with 114/590 (19.3%) representing a BMI of 35 or greater, comprising the analysis group. The agreement for detection of hrHPV was equivalent across BMI categories. Over a third (36.8%) of participants in Class II (BMI: 35-40) and Class III (BMI > 40) categories had delayed or avoided their cervical cancer screening, and 91% reported that they would be more likely to stay up to date with routine screening if an at-home self-collect option were available. Preferences for self-collect among women in Class II + categories were higher for a self-collect option for screening, reporting that SC made them feel more in control of their experience. In women with a BMI ≥ 35, cervical cancer screening by SC with this uniquely designed device demonstrated equivalent or superior HPV detection performance and was strongly preferred by participants. Offering this option could improve screening rates in women with BMI ≥ 35, a group that represents a significant portion of the US population who delay screening and help reduce disparities in cervical cancer incidence and outcomes.

Laparoscopic multi-bipolar radiofrequency ablation of fibroids: impact on quality of life

To evaluate the effectiveness of multi-bipolar radiofrequency ablation compared to standard laparoscopic myomectomy in treating uterine fibroids, focusing on women's quality of life. Retrospective observational cohort study. La Conception Hospital, APHM-Marseille, France. 50 women with symptomatic fibroids treated between December 2021 and December 2023. Laparoscopic radiofrequency ablation or conventional laparoscopic myomectomy. After excluding patients who did not complete the preoperative quality-of-life questionnaire, 34 underwent myomectomy and 16 radiofrequency ablation. At 3 months, no significant differences were observed in HRQOL improvement (9.2 ± 34.3 vs 24.2 ± 28.2, p = 0.14), SSS (- 27.5 ± 31.5 vs - 23.3 ± 33, p = 0.66), or FSFI (0.9 ± 14.7 vs - 1.5 ± 10.8, p = 0.40). The 6-month outcomes also showed no significant difference. Baseline fibroid-specific quality of life was significantly and negatively associated with improvement (p < 0.05). Both procedures improved quality of life and reduced fibroid-related symptoms at 3 and 6 months, with no significant difference. Myolysis showed fewer peri- and postoperative complications, suggesting a better safety profile and potential as a conservative treatment option. The ethics committee of Aix Marseille University approved this study on April 18, 2024, under the reference number 2024-04-18-08.

Clinical comparison of laparoscopic and open surgical approaches for uterus-preserving myomectomy: a retrospective analysis on patient-reported outcome, postoperative morbidity and pregnancy outcomes

Abstract Purpose Uterine fibroids pose clinical challenges due to varied symptoms and impact on fertility. Aim of this research is to compare open and laparoscopic myomectomy, with focus on evaluating their effects on patients' quality of life and analyzing their implications for pregnancy outcomes. Methods This retrospective study compares open and laparoscopic myomectomy outcomes in 168 patients treated October 2017 and July 2023. Preoperative characteristics and postoperative outcomes in terms of symptoms and pregnancy outcomes were examined. Results The patient cohort comprised patients with a high symptom burden. Only 51.2% expressing a desire for future pregnancies, highlighting diverse motivations for uterus-preservation. No significant differences were observed in preoperative symptoms. Larger and multiple myomas were associated with a higher likelihood of laparotomy. Recurrence rates were lower after laparoscopy (10.2% vs. 23.8%, p = 0.02). Cesarean section recommendations were more frequent post-laparotomy group (36.6% vs. 86.6%, p = 0.000). Morbidities and satisfaction showed no significant differences between approaches, with slightly better bleeding improvement after laparotomy. Despite similar pregnancy outcomes, a high proportion of patients did not conceive postoperatively (75.4%). Among patients who became pregnant postoperatively (n = 31), most patients conceived after one year or more, with no dependence on the surgical approach (p = 0.227). Conclusion Both open and laparoscopic myomectomy surgeries showed high patient satisfaction, symptom alleviation, and comparable pregnancy results. A preference emerged for laparoscopy in terms of cesarean section recommendations and recurrence risk. Laparoscopic procedures tended to offer higher operative satisfaction and fewer complications. The study emphasized the complexity of therapeutic decision-making.

Co-cultivation of human granulosa cells with ovarian cancer cells leads to a significant increase in progesterone production

Abstract Purpose In humans, granulosa cells (GCs) are part of the follicle and nourish the growing oocyte. GCs produce estrogen and, after ovulation, progesterone. They are embedded in a multicellular tissue structure of the ovary, which consists of a variety of different cell types that are essential for the physiological function of the ovary. However, the extent to which individual ovarian cell types contribute to overall functionality has not yet been fully elucidated. In this study, we aim to investigate the effects of co-culturing human granulosa cells with ovarian cancer cells on their progesterone and estrogen production in an in vitro model. Methods After seeding, the cells were stimulated with 200 µM forskolin in DMEM for 72 h and the medium of the different cell culture experiments was collected. Subsequently, progesterone and oestradiol concentrations were determined using an Elisa assay. Results Morphologically, it was striking that the cells self-organize and form spatially separated areas. Compared to culturing granulosa cells alone, co-culturing human granulosa cells together with the ovarian cancer cell line OvCar-3 resulted in a significant increase in progesterone production (20.3 ng/ml versus 50.2 ng/ml; p  &lt; 0.01). Conclusions Using a simple in vitro model, we highlight the importance of cellular crosstalk between different ovarian cells in a complex cellular network and that it strongly influences granulosa cell hormone production. This could have potential implications for the procedure of transplanting endocrine tissues after cryopreservation, as it highlights the importance of survival of all cells for the functionality of the transplanted tissue.

Surgery due to mechanical bowel obstruction in relapsed ovarian cancer: clinical and surgical results of a bicentric analysis of 87 patients

Abstract Introduction Mechanical bowel obstruction is a frequent acute and life-threatening event in relapsed ovarian cancer. Salvage surgery after failure of all conservative approaches, resulting in short bowel syndrome (SBS) constitutes a therapeutic dilemma. Our aim was to evaluate patients’ surgical and clinical outcome in these highly palliative situations. Previous, limited, data reported a high morbidity and mortality. However, recent surgical and therapeutical improvements in relapsed ovarian cancer (ROC) offer better identification of patients who might benefit from surgery in an effort to extend the window of opportunity to subsequently offer these patients novel systemic therapeutic approaches. Material and methods All subsequent ROC patients between 2012 and 2017 with acute mechanical bowel obstruction who underwent salvage extraperitoneal en bloc intestinal resection were retrospectively identified. Data were collected from two ESGO certified Ovarian Cancer Centers of Excellence (Charité Berlin and Imperial College London) and systematically evaluated regarding surgical and clinical outcomes. Results Overall, 87 ROC patients were included in the analysis (median age 56 years, range 24–88), 47% were platinum resistant. High grade serous was the most common histology (76%) while most of the patients (67%) had at least two previous lines of treatment. Mean observed OS was 7.8 months. After salvage surgery, 46% of the patients had a residual small bowel length &lt; 180 cm and 18% &gt; 180 cm resulting in 41% in need of total parental nutrition. In 80% of the patients a permanent stoma was necessary. 30d morbidity and mortality was 74% and 10%, respectively. More than half of the patients were able to receive further courses of chemotherapy after surgery. Discussion Salvage surgery for bowel obstruction in ROC patients needs careful consideration and identification of optimal surgical candidates to have the maximal therapeutic benefit. Despite the challenging morbidity profile, most patients managed to proceed to subsequent novel and conventional systemic treatment and so have their window of therapeutic opportunity extended.

Galectin-8 and -9 as prognostic factors for cervical cancer

Abstract Purpose Galectins are carbohydrate-binding proteins with multiple effects on cell biology. Research shows that they play an important role in tumor development and progression. Therefore, in this study, the presence of Galectin-8 and -9 (Gal), both already known as prognostic factors in other tumor entities, were investigated in cervical cancer. Our aim was to examine the association of Gal-8 and -9 expression with histopathological markers and survival of the patients. Methods Gal-8 and -9 expression was investigated in 250 cervical cancer samples by immunohistochemistry. The staining was evaluated using the immunoreactive score (IRS). The results were correlated to clinical and pathological data. The correlation of Gal-8 and -9 expression with overall and relapse-free survival was analyzed. Results Expression of Gal-8 was associated with negative N-status and lower FIGO status. Detection of Gal-9 was connected to negative N-status and lower grading regarding all specimens. A correlation of Gal-9 with lower FIGO status was detected for squamous cell carcinoma (SCC) only. Expression of Gal-8 was associated with relapse-free survival of SCC patients in a positive manner. Gal-9 expression was associated with better overall survival. Conclusion Our results suggest that expression of both galectins is inversely associated with tumor stage and progression. Gal-8 expression is associated with relapse-free survival of patients with SCC, while presence of Gal-9 in cervical cancer is associated with a better prognosis in regard of overall survival.

Learning curves, safety, and experiences of a tertiary surgical center in the introduction of robotic-assisted surgery in gynecologic oncology

Abstract Background The dynamic development towards robotic-assisted surgery particularly affects operative gynecology. The analysis of operative data from robotic-assisted procedures since the first application at a surgical center provides valuable insights into the introduction phase and integration of the DaVinci system into routine clinical operations, as well as their impact on patient care. The aim of this work was to specifically examine the learning curve progression and to present the trend of the professionalization process in implementing the methodology in gynecologic oncology. Materials and methods A retrospective data analysis was conducted of the first n  = 107 patients who underwent surgery for a gynecological malignancy with the DaVinci surgical system at the University Medical Center Freiburg between 2020 and 2022. Classic operative parameters were evaluated, including preparation time, skin-to-skin time, console time, and the resulting learning curves of the surgeons and the operative team (including CUSUM analysis and linear regression models). Additionally, perioperative patient characteristics were recorded (e.g., blood loss, length of hospitalization, conversion rate). Results The average operative preparation time is 26.11 ± 8.13 min. The maximum value (CUSUM peak) is at approximately 20 performed procedures, indicating that the processes of operative preparation were mastered after this number of operations. The average skin-to-skin time is 172.84 ± 71.68 min (range 43–387 min), whereby after an initial reduction in skin-to-skin time within the first 30 cases, there was a slight increase in the further course with renewed reduction from approximately 65 procedures. The average console time for all tumor entities is 131.98 ± 63.74 min; for the most common operative indication (endometrial cancer, n  = 61), it is 109.89 ± 52.04 min (range 48–221 min). In the surgeons' learning curves, the two surgeons with the most procedures show a CUSUM peak after 11 and 22 procedures, respectively. The average length of stay is 5.00 days (± 2.30). A total of two conversions occurred (conversion rate = 1.9%). Discussion Upon evaluation of the first n  = 107 DaVinci operations, rapid learnability of robotic-assisted operations was demonstrated. The conversion rate was low at 1.9%. A positive effect on the learning curve of individual surgeons was evident after approximately 20 procedures. Both the preparation time and the skin-to-skin time could be rapidly reduced, so that integration into routine clinical operations was possible without problems.

Patient perspectives on perioperative telemedicine in female malignancies: the role of age, digital experience, and privacy concerns

Telemedicine offers new opportunities in perioperative care, particularly for patients with female malignancies. This study investigated factors influencing patient acceptance of telemedical services during the preoperative phase. Between May and November 2022, 145 patients with breast or gynecologic malignancies completed a structured questionnaire in a cross-sectional study during preoperative consultation. Sociodemographic factors, digital experience, and privacy concerns were assessed. Data were analyzed using descriptive statistics, t-tests, Chi-square, Mann-Whitney U-tests, and binary logistic regression. Overall, 69% of patients expressed agreement with perioperative telemedicine. Younger age (mean 50.6 vs. 59.3 years; p = 0.001) and greater digital experience, especially video call usage (p = 0.005), significantly predicted approval. The most preferred modality was browser-based video consultation (47%; p = 0.007). No significant associations were found for distance to clinic (p = 0.672), EQ-VAS score (p = 0.597), or number of prior clinic visits (p = 0.331). Barriers included data protection concerns (p < 0.001) and discomfort with receiving sensitive information via telemedicine (p < 0.001). Most patients view telemedicine as a valuable supplement to traditional care. Acceptance depends on age, digital literacy, and the perceived sensitivity of clinical communication. Tailored implementation respecting patient preferences is essential.

Impact of risk and lifestyle factors on therapy goals in the treatment of breast cancer and gynecological cancer patients with integrative medicine

Abstract Background As a result of advancements in the diagnosis and therapy of cancer, the prognosis for cancer patients has significantly improved. The benefits of a significantly enhanced survival time lead to a more extensive concern with quality of life and managing the side effects during oncological treatment. Implementing integrative medicine strategies has been found to reduce the side effects of therapy and disease. In 2021 the S3 guideline on complementary medicine in oncology was published for the first time, which takes a stand on the most common aspects of complementary and integrative medicine in Germany. The aim was to see whether a previous healthy life style impacts the success of integrative medicine for patients. Methods Within the framework of a cross-sectional study over 15 months, 120 cancer patients were monitored at a standardized integrative medicine consultancy service at the University Integrative Medicine Center of the University Hospital Erlangen, Department of Gynecology and Obstetrics. The basic questionnaire consisted of questions on socioeconomic background information, lifestyle factors, such as dietary habits or smoking behavior, as well as information on the gynecological situation. Furthermore, an evaluation based on patient-reported therapy goals concerning the reduction of side effects of conventional cancer treatments, enhancement of disease-related quality of life and better stress and disease management, active participation in cancer treatments, mind–body stabilization, and improvements in coping strategies were assessed. In addition, the impact of patient characteristics and lifestyle on the subjective achievement of these outcomes was evaluated to set the answers in context and show its influence. Statistical analysis was performed using SPSS Statistics for Windows version 26 (IBM Corporation, Armonk in New York, USA). Mean, standard deviation, minimum, and maximum were calculated for age and BMI. The other characteristics regarding demographics, lifestyle, tumor disease, and therapy were analyzed based on their respective absolute and relative frequencies. Results A large majority of the patients' participation goal was to reduce cancer-related side effects (90.8%), second were the aspects of “Improvement of the disease-related quality of life “(72.5%). In both cases, this common goal was only fully achieved for about one quarter of the patients (25.7%/24.1%), but partially achieved in more than half of the asked patients (53.2%/52.9%). Half of the patients reported that they achieved active participation in cancer treatment with integrative medicine. Around 50% partially achieved stabilization of the body, soul, and spirit, stress, disease management, improvement in cancer-related quality of life, and reduced the side effects of conventional cancer therapies. The success of integrative therapy was independent of age, BMI, family status, children, level of education, insurance type, alcohol and tobacco consumption, sport, low-fat diet, daily fruit and vegetable servings, interest in diets, and previous use of diets. Conclusions and discussion Using a standardized procedure in integrative medicine allows patients to receive high-quality care. The previous standard of living has no effect on the benefits of integrative medicine for the patient. The goals through the use of integrative medicine could be achieved by all patient groups. It is highly encouraged to incorporate counseling and evidence-based integrative medicine into the clinical routines of cancer centers and adapt postgraduate medical education. Finally, the evidence base for the recommendations should also be strengthened by further research into the use of integrative medicine.

The impact of Enhanced Recovery after Surgery (ERAS) pathways with regard to perioperative outcome in patients with ovarian cancer

Abstract Purpose Major surgery for ovarian cancer is associated with significant morbidity. Recently, guidelines for perioperative care in gynecologic oncology with a structured “Enhanced Recovery after Surgery (ERAS)” program were presented. Our aim was to evaluate if implementation of ERAS reduces postoperative complications in patients undergoing extensive cytoreductive surgery for ovarian cancer. Methods 134 patients with ovarian cancer (FIGO I-IV) were included. 47 patients were prospectively studied after implementation of a mandatory ERAS protocol (ERAS group) and compared to 87 patients that were treated before implementation (pre-ERAS group). Primary endpoints of this study were the effects of the ERAS protocol on postoperative complications and length of stay in hospital. Results Preoperative and surgical data were comparable in both groups. Only the POSSUM score was higher in the ERAS group (11.8% vs. 9.3%, p &lt; 0.001), indicating a higher surgical risk in the ERAS group. Total number of postoperative complications (ERAS: 29.8% vs. pre-ERAS: 52.8%, p = 0.011), and length of hospital stay (ERAS: 11 (6–23) vs pre-ERAS: 13 (6–50) days; p &lt; 0.001) differed significantly. A lower fraction of patients of the ERAS group (87.2%) needed postoperative admission to the ICU compared to the pre-ERAS group (97.7%), p = 0.022). Mortality within the ERAS group was 0% vs. 3.4% (p = 0.552) in the pre-ERAS group. Conclusion The implementation of a mandatory ERAS protocol was associated with a lower rate of postoperative complications and a reduced length of stay in hospital. If ERAS has influence on long-term outcome needs to be further evaluated.

Evaluation of endocervical curettage (ECC) in colposcopy for detecting cervical intraepithelial lesions

Diagnostic challenges in colposcopy arise especially in women aged 50 or older, with postmenopausal status and transformation zone type 3 (TZ3). Endocervical curettage (ECC) is a valuable tool for diagnosing intracervical lesions. The aim of this retrospective analysis was to evaluate the use of ECC in colposcopy for detecting cervical intraepithelial lesions. A retrospective study was carried out of colposcopies performed in the certified Dysplasia Unit at Erlangen University Hospital between July 2016 and June 2023. Pap and human papillomavirus (HPV) results were correlated with the histologic findings via ECC, obtained during examinations or surgery. The primary outcome was the rate of accuracy between the colposcopic and histologic findings with regard to cytology, age of patients, and type of transformation zone (TZ). A total of 429 colposcopies in 413 women with histologic samples obtained via ECC were included in the final analysis. In all, 355 women had TZ3. Among patients with TZ3, evidence of high-grade lesions and invasive carcinoma was also found in women with normal or low-grade abnormal cytology. For patients with normal colposcopic findings, cervical intraepithelial neoplasia (CIN) 2 and CIN 3/adenocarcinoma in situ (AIS) were found in 56 patients (16%), and invasive carcinoma was found in four patients (0.1%). This analysis suggests that ECC is a valuable tool in the diagnosis of cervical intraepithelial neoplasia, especially for patients who present with a normal colposcopy of the cervix and vagina but have either recurrent abnormal cytologic findings or high-grade abnormal cytology indicating CIN 2 + .

Certification as dysplasia unit and its impact on large loop electrosurgical excision (LEEP)

Abstract Purpose This study evaluates the overall treatment indicators and outcomes of patients who underwent loop electrosurgical excision procedure (LEEP) at the Department of Women’s Health Tübingen and the impact of certification as a dysplasia unit on treatment quality. Methods Retrospective data analysis of 1596 patients from 2013 to 2018 who underwent LEEP excision at the Department of Women’s Health Tübingen. Data of cytology, colposcopy, biopsy, LEEP histology, repeat LEEP histology and general characteristics were collected and analyzed descriptively. Results 85.4% (1364) of patients had CIN 2 + and 14.6% (232) had CIN 1 or normal findings on LEEP histology. The proportion of CIN 2 + excisions increased significantly from 82.4% in 2013 to 89% in 2018. The concordance of HSIL biopsy and LEEP histology was 89.1% in 2013 and 92.6% in 2018. In 2018, more biopsies and colposcopies were performed before excision. Complete resection (R0) was achieved in 88.3% of all excisions. R0 rates in patients with CIN 3 increased in 2014–2017 compared to 2013, resulting in fewer Re-LEEP excisions and hysterectomies. Conclusion Certification as a dysplasia unit and the associated requirements have improved the diagnostic quality for patients with cervical dysplasia undergoing LEEP. This was demonstrated by several treatment indicators such as the number of colposcopies and biopsies and treatment outcomes such as an increased proportion of CIN 2 + excisions and R0 resections.

Characterization and clinical management of abnormal cytology findings in pregnant women: a retrospective analysis

AbstractPurposeThe diagnosis of cervical intraepithelial neoplasia during pregnancy poses a great challenge to the treating clinician and the patient. According to the current guidelines, watchful waiting during pregnancy can be justified. Only in cases of invasion, immediate treatment may be indicated. However, few data are available on the management of cervical dysplasia during pregnancy. Further research is important for counselling affected women.MethodsData of pregnant patients with suspected cervical dysplasia who presented to the University Women’s Hospital Tübingen between 2008 and 2018 were evaluated retrospectively. Colposcopic, cytologic, and histologic assessment was performed for diagnosis. Data on remission, persistence and progression of disease based on histologic and cytologic assessment and the mode of delivery were correlated.Results142 patients were enrolled. Cytology at first presentation was PAPIII (-p/-g) in 7.0%, PAPIIID (IIID1/IIID2) in 38.7%, PAPIVa (-p/-g) in 50.0%, PAPIVb (-p) in 2.8%, and PAPV (-p) in 1.4%. All cases with suspected invasion were recorded at the initial presentation. Complete histological or cytological remission was observed in 24.4%, partial remission in 10.4%, persistence in 56.3%, and progression in 8.9%. In two cases (1.5%) progression to squamous cell carcinoma occurred.ConclusionsWatchful waiting for cervical intraepithelial neoplasia during pregnancy seems to be sufficient and oncologically safe. It is important to exclude invasion during pregnancy, to perform frequent colposcopic, cytologic and histologic examinations and to ensure a postpartum follow-up examination to initiate the treatment of high-grade lesions. Spontaneous delivery seems to be safe in patients with cervical dysplasia, Caesarean section is not indicated.

Incidence, risk factors, and outcomes of ovarian metastasis in early-stage cervical cancer: a population-based analysis of 983 patients

Abstract Purpose To assess the incidence, risk factors, and prognostic impact of ovarian metastasis in early-stage cervical cancer using a large population-based registry. Methods We retrospectively analyzed 983 patients with cervical cancer classified as pT1a1–pT2b according to the TNM system treated with primary surgery and bilateral oophorectomy. The association between clinicopathological variables and ovarian metastasis was evaluated using Chi-square tests and binary logistic regression. Survival outcomes were assessed with Kaplan–Meier curves and Cox regression. Results Ovarian metastases were identified in 0.8% of cases ( n  = 8). Histologic subtype was significantly associated with ovarian metastasis ( p  = 0.010). In multivariate logistic regression, adenocarcinoma histology was an independent predictor of metastasis (OR 9.94, 95% CI 1.99–49.6, p  = 0.005). Patients with ovarian metastases had significantly worse disease-free and overall survival ( p  &lt; 0.001). Due to the rarity of events, multivariable survival analysis incorporating treatment parameters was limited. Conclusion Ovarian metastasis is rare in early-stage cervical cancer but associated with significantly impaired prognosis. Adenocarcinoma histology was independently associated with ovarian metastasis and may be considered when discussing ovarian preservation, although validation in larger cohorts is warranted. These findings support the individualized selection of patients for ovary-sparing surgery.

Genetic tumor syndromes in female cancer: insights into inherited cancer predisposition and clinical implications

Abstract A relevant proportion of malignancies predominantly or exclusively affecting women, including breast and gynecologic cancers, is attributable to hereditary tumor syndromes, profoundly impacting cancer risk, prognosis, and therapeutic management. Today, the routine use of comprehensive germline panels has shifted the focus from solely pathogenic BRCA1/2 variants to include numerous pathogenic variants of other high- and moderate-risk genes. A broad spectrum of genetic alterations has been identified as causative for Hereditary Breast and Ovarian Cancer syndrome (HBOC), encompassing not only BRCA1 and BRCA2 , but also PALB2 , ATM , BARD1 , CHEK2 , BRIP1 , RAD51C , and RAD51D . Beyond HBOC, numerous additional hereditary tumor syndromes are of significance in senologic and/or gynecologic oncology, including Li-Fraumeni syndrome, Lynch syndrome, DICER1 syndrome, Hereditary Diffuse Gastric Cancer, Neurofibromatosis type 1, Peutz-Jeghers syndrome, PTEN hamartoma tumor syndrome, Tuberous Sclerosis, and pathogenic variants in NBN and SMARCA4 . Affected individuals are offered specialized surveillance to enable early detection or even prevention of cancer. In addition to regular clinical examinations and imaging, preventive strategies may include risk-reducing surgery. Pathogenic germline variants also influence therapeutic management of cancer patients. For specific indications, targeted therapies are available, for example PARP [poly (ADP-ribose) polymerase] inhibitors for pathogenic BRCA variant carriers across multiple tumor entities. Optimal management requires interdisciplinary coordination, encompassing genetic counseling, early detection, and risk-reducing strategies within specialized centers. This review provides a comprehensive overview of hereditary tumor syndromes predisposing to breast and gynecologic malignancies, with a focus on genetic basis, associated cancer risks, and implications for clinical management. By delineating these syndromes, it aims to assist clinicians in recognizing hereditary cancer predisposition and in guiding affected individuals within routine senologic and gynecologic practice.

Between research and introduction to clinical routine—Experience with niraparib from the compassionate use program in Germany (NOGGO Register Analysis)

Abstract Purpose Ovarian cancer (OC) is frequently diagnosed at a late, advanced stage, resulting in poor survival outcomes. PARP inhibitors like niraparib have shown significant efficacy in high-grade OC, particularly in tumors with homologous recombination deficiency, including BRCA mutations. This study aimed to evaluate dose modifications, safety, tolerability, and the impact on quality of life associated with niraparib in real-world clinical practice. Methods This non-interventional, register-based study included patients with platinum-sensitive recurrent OC who received niraparib as part of the compassionate-use program (CUP) in Germany. Clinical baseline characteristics, treatment data, adverse events (AEs), and quality-of-life measures were collected both prospectively and retrospectively across 14 centers. Data analysis was performed using descriptive statistical methods. Results Overall, 68 female patients were enrolled in the CUP register. Most patients had good performance status, with no significant comorbidities or concomitant medications. The most frequently reported AEs associated with niraparib were thrombocytopenia, fatigue, and nausea. Approximately half of patients required dose adjustments. AEs were less common in patients with normal physical examination findings, better ECOG performance status, and absence of comorbidities. Prior use of PARP inhibitors or previous treatment-related side effects increased the likelihood of AEs during niraparib therapy. The median treatment duration was 182 days, with disease progression being the most common reason for discontinuation. Conclusion Niraparib treatment within the German CUP demonstrated favorable safety and tolerability profiles, supporting its effectiveness in a real-world setting for patients with recurrent OC. These findings are consistent with results from clinical trials, further reinforcing the role of niraparib in this patient population.

Development of medical freezing measures in women during the last decade from 2014 to 2023: registry data of the tri-national network FertiPROTEKT

Abstract Research question To what extent have fertility preservation interventions evolved between 2014 and 2023, and what factors have influenced changes in their utilization and prevalence? Design Based on the Ferti PROTEKT registry, comprising 163 centres across Germany, Austria, and parts of Switzerland, the quantitative development of ovarian stimulation for oocyte cryopreservation and ovarian tissue cryopreservation was evaluated from 2014 to 2023. Analyses were stratified according to the kind of participating centre, patient age, and the spectrum of underlying diseases. In addition, data were statistically compared for the periods 2014/2015 (P1) and 2022/2023 (P2). Results Approximately 14,000 women received counselling across all three countries between 2014 and 2023. Among these, 3,996 females underwent ovarian stimulation for oocyte cryopreservation, and 3,478 underwent ovarian tissue cryopreservation. The number of oocyte cryopreservation cycles increased substantially from P1 to P2, whereas the number of ovarian tissue cryopreservation procedures remained relatively stable. The increase in oocyte cryopreservation was substantially greater in private centres (197% increase: 308 to 916 cycles) compared to public institutions (39% increase: 818 to 1,136 cycles; p &lt; 0.001). The rise in oocyte cryopreservation cycles parallels an increase in breast cancer cases presenting for fertility preservation; this temporal coincidence suggests a potential association but does not establish causation. The predominance of breast cancer patients also influenced the age distribution of oocyte cryopreservation cases. Among oocyte cryopreservation procedures, absolute numbers increased across all age groups up to 40 years, with the largest absolute increase in women aged 31–40 years (212 to 732 cycles, 245% relative increase).The overall age distribution of procedures changed only slightly, although younger patients were more likely to undergo ovarian tissue cryopreservation. Additionally, new indications such as endometriosis and gender dysphoria have become increasingly relevant over the past 5 years. Conclusion The number and distribution of fertility preservation procedures have changed notably during the last decade, driven primarily by shifts in the reimbursement strategies and the type of centres providing care. These developments should be carefully considered in the future design and implementation of fertility preservation programmes. However, decisions regarding specific fertility-preserving interventions must also be guided by scientific evidence.

Clinical and ultrasound characteristics of primary fallopian tube carcinoma: a single-institution retrospective study of 280 cases

What is already known about this topic - Years ago, the clinical and ultrasound characteristics of rare fallopian tube carcinomas were summarized on the basis of a limited sample size. Recent evolutions in pathological diagnostic criteria have substantially increased reported morbidity; however, clinical and ultrasound feature descriptions have remained outdated What this study adds - We retrospectively reviewed the clinical and ultrasound features of a large sample of patients with primary fallopian tube carcinoma. We identified several new clinical and ultrasound features that may be useful for the early clinical diagnosis of primary fallopian tube carcinoma. How this study might affect research, practice or policy - The treatment strategy for primary fallopian tube carcinoma parallels that for ovarian malignancy; however, primary fallopian tube carcinoma lesions are characterized by early dissemination. This study elucidated several unique features of primary fallopian tube carcinoma, which enable early diagnosis and improve patient prognosis. This study aimed to describe the sonographic and clinical characteristics of primary tubal carcinoma, a rare gynecological malignancy. This was a retrospective, single-center study that included 280 patients with postoperative histologically diagnosed fallopian tube carcinoma. All patients underwent preoperative ultrasound and surgery at Obstetrics and Gynecology Hospital of Fudan University from 2020-2024. Clinical data and ultrasound data were collected. The most common complaint was abdominal pain/bloating (35.71%), whereas 42.14% were asymptomatic. High-grade serous carcinoma was the predominant histological type (95.36%). Unilateral masses were more common (47.14%). Oval masses were the most prevalent ultrasonic appearance (58.15%). Endometrial fluid was observed in 28.57% cases. In 67.15% of cases, ultrasound accurately described the dominant mass in accordance with the intraoperative observations. The ovarian-dominant masses had significantly greater CA125 levels and larger diameters than the tubal-dominant masses did. Abdominal pain/distension and the presence of endometrial fluid should receive increased attention in the diagnosis of tubal cancer. A characteristic pattern of "large metastases and small primary lesions" was found via tubal cancer sonography. Oval lesions were observed more frequently than sausage-shaped lesions in fallopian tube cancer, with the masses predominantly being solid or predominantly solid.

Earlier is not always better: Optimal time to initiate adjuvant chemotherapy after surgery for ovarian cancer

Tumor resection followed by adjuvant chemotherapy constitutes the cornerstone of ovarian cancer (OC) treatment. This study aimed to evaluate the impact of the time to chemotherapy (TTC) after primary surgery on the survival outcomes of patients with OC. Patients with OC at any stage who underwent primary surgery followed by adjuvant chemotherapy between 2000 and 2021 were included in the analysis. Data were obtained from the Cancer Registries of Aachen and nine hospitals in Saxony-Anhalt. Patients were stratified into three subgroups based on the timing of chemotherapy initiation: early (≤ 21 days), intermediate (22-35 days) and late (> 35-180 days). The impact of TTC on progression-free survival (PFS) and overall survival (OS) was assessed using multivariate Cox proportional hazard models, both in complete case analysis and with multivariate imputation by chained equations to account for missing data. A total of 1699 patients with OC (mean age: 61.4 ± 12 years) started adjuvant chemotherapy 32.2 ± 24.6 days after surgery. For OS, the optimal TTC was identified at 26 days post-surgery. Compared with the intermediate group, both earlier and later initiation of chemotherapy were associated with worsened OS (Hazard Ratio (HR) = 1.34, 95%CI 1.23-1.60, p < 0.05 and HR = 1.38 95%CI 1.14 -1.68; p < 0.001, respectively). The optimal timing for initiating adjuvant chemotherapy appears to be between 22 and 35 days after primary surgery for ovarian cancer. Remarkably, an earlier start of chemotherapy did not confer a survival advantage, possibly due to the need for adequate recovery after surgery.

Intergroup statement: opportunistic salpingectomy—molecular pathology, clinical outcomes and implications for practice (German Ovarian Cancer Commission, the North-Eastern German Society of Gynecologic Oncology (NOGGO), AGO Austria and AGO Swiss)

Abstract Opportunistic salpingectomy is defined as the removal of both fallopian tubes as part of a surgical procedure planned for other reasons. The goal is primary prevention of ovarian cancer. The procedure is offered to patients who are not known to be at increased risk of developing ovarian cancer. This is in contrast to high-risk patients with a germline mutation, particularly BRCA1/2, for whom risk-reducing salpingo-oophorectomy is generally recommended. Premalignant cells and early occult cancers have been detected in RRSO specimens in the fimbrial funnel region, but not on the ovarian surface. The presence of mitoses, nuclear atypia, and staining in response to p53 mutation in these serous intraepithelial carcinomas (STIC) indicates the initial genetic changes in the fallopian tube mucosa that subsequently lead to the development of advanced peritoneal carcinomas. The identification of STICs has challenged the traditional view of the pathogenesis of the largest subset of epithelial ovarian cancers, namely the high-grade serous cancers of the ovary, fallopian tubes, and peritoneum. In a position statement published in 2015, the German Arbeitsgemeinschaft Gynäkologische Onkologie (AGO) Kommission Ovar recommended that patients be informed of the latest findings on the development and potential benefits of bilateral salpingectomy at the time of hysterectomy. This may reduce the risk of developing ovarian cancer later in life. However, the scientific evidence has not been deemed sufficient to justify a general recommendation. In the same year, the Austrian AGO published a statement recommending the broad use of opportunistic salpingectomy without reservation. This review examines the current status of molecular pathology studies, recent evidence on the clinical implications of STIC, new data on the use of opportunistic salpingectomy, and published patient outcomes since then. The question of whether the potential benefit of opportunistic salpingectomy, outweighs the potential harms associated with surgical morbidity, which have not been conclusively excluded, should be revisited in light of these recent data.

Outcomes and prognostic factors in patients with synchronous endometrial and ovarian cancer

To analyze prognostic factors and survival outcomes in patients with synchronous endometrial and ovarian cancer (SEOC) to guide clinical management. We conducted a retrospective cohort study of patients diagnosed with SEOC at Peking University People's Hospital between January 2004 and December 2024. Clinicopathological data were collected, and oncological outcomes, including progression-free survival (PFS) and overall survival (OS), were analyzed along with their associated prognostic factors. Among 64 included patients, vaginal bleeding was the predominant presenting symptom. Thirty-six patients were diagnosed with concordant endometrioid carcinoma, which was the most common histological type. All patients underwent surgical treatment, among whom 56 received platinum-based chemotherapy postoperatively, with a platinum sensitivity rate of 67.9%. The median PFS and OS were 27 months (range 3-215) and 41 months (range 7-246), respectively. On multivariate analysis, advanced FIGO stage of ovarian cancer (HR = 2.764; 95% CI 1.169-6.536, P = 0.021) independently predicted worse PFS, while platinum resistance (HR = 6.962; 95% CI 2.052-23.619, P = 0.002) was significantly associated with reduced OS. In this cohort, platinum sensitivity was observed in 67.9% of cases. The advanced ovarian FIGO stage and platinum resistance independently correlated with inferior survival, underscoring the urgent need for tailored therapeutic strategies and intensified surveillance in platinum-resistant SEOC.

Fertility-sparing strategy in a rare case of highly malignant Dicer-1-associated sarcoma of the cervix

Abstract Introduction We present the rare case of an 18-year-old patient with a Dicer-1 mutation-associated sarcoma of the cervix uteri. Case The patient presented with irregular vaginal bleeding in July 2022. The clinical examination showed an exophytic tumor of the cervix, uterus and ovaries were normal in sonogram. The tumor of the cervix was resected, followed by a diagnostic hysteroscopy and abrasion of the uterine cervix and cavity. Hysteroscopy showed normal findings of the cervix and uterus. After diagnosis of a highly malignant Dicer-1 mutation-associated sarcoma of the cervix, cryopreservation of oocytes was realized. Based on the principle of obtaining maximum oncological safety while preserving fertility in this 18-year-old patient, we recommended chemotherapy rather than radiation with its far severe implications on the patient´s reproductive organs. 4 cycles of chemotherapy consisting of doxorubicin and ifosfamide were applied until December 2022. After re-staging in December 2022 via CT scan and MRI, the abdomen and pelvis as well as control hysteroscopy and abrasion were unremarkable. Until now, the patient is tumor free. Discussion Primary sarcomas of the cervix are very rare. Recent literature hints towards a distinct DICER-1 sarcoma entity characterized by specific mutational clusters. Limited follow-up data suggested that DICER1-mutant tumors might exhibit a less aggressive clinical course than DICER1-wild-type tumors. Conclusion Decision-making in case of rare histological entities with sparse recommendations in the literature poses a challenge to the treating physician. Treatment strategies should consider oncological safety as well as options of preserving fertility. Gonadotoxic potential of different strategies should be taken into consideration and discussed in detail with the affected patient.

Ultrasonographic diagnosis of adnexal masses: interobserver agreement in the interpretation of videos, using IOTA terminology

Abstract Objectives Aim of this study is to estimate interobserver agreement in classifying adnexal tumors using IOTA terms, simple rules and subjective assessment. In addition, we related observers’ accuracy with their experience in gynecological ultrasonography and the year of IOTA certification. Methods Eleven observers with three different levels of experience evaluated videoclips of 70 adnexal masses, defining tumor type according to IOTA terms and definitions, classifying the mass using IOTA Simple rules and Subjective assessment as well as providing Color Score evaluation. Sensitivity, specificity and area under the ROC curve were calculated and the year of IOTA certification was related with operators’ accuracy through Pearson correlation coefficient. Interobserver agreement was estimated calculating percentage of agreement, Fleiss kappa and Cohen’s kappa. Results We found a positive correlation between the year of IOTA certification and operators’ accuracy (Pearson coefficient 0.694), especially among the observers with the least experience, the residents (p = 0.003). For tumor type classification, identification of papillary projections and classification of tumors using subjective assessment, agreement among all observers was moderate (Fleiss kappa 0.455, 0.552, and 0.476, respectively) and increased with the years of experience. Agreement in the application of Simple Rules was moderate in all examiners with IOTA certification, with Fleiss kappa in the range of (0.403, 0.498). For Color Score assignment interobserver agreement among all observers was fair (Cohen’s kappa 0.380). Conclusions Even among expert examiners, the results of adnexal lesion assessment can be inconsistent. Experience impacts on accuracy and agreement in subjective assessment, while the application of Simple Rules can mitigate the role of experience in interobserver agreement. The knowledge of IOTA models among residents seams to improve their diagnostic accuracy, showing the benefits of IOTA terminology for in training sonographers.

Does controlled ovarian hyperstimulation in women with a history of borderline tumor influence recurrence rate?

Abstract Purpose To determine the recurrence rate in the women with controlled ovarian hyperstimulation after a history of borderline ovarian tumors (BOT). Methods This was a retrospective analysis of 275 patients with BOT undergoing surgery for fertility preservation in our hospital between 2001 and 2017. Cases were divided into an assisted reproductive technology (ART) treatment group (n = 15) and a non-ART treatment group (n = 260). We compared the recurrence rate, survival rate and pregnancy outcomes between these two groups. Results The ART group had a higher recurrence rate (33.33% vs. 10.80%, P = 0.023). Survival analysis indicated that the recurrence time in patients undergoing ART was significantly shorter (P = 0.026). A low pregnancy rate before diagnosis, and high intraoperative blood loss, were associated with postoperative ART treatment (P &lt; 0.05). Multivariate analysis showed that ART treatment and bilateral lesions both significantly increased the risk of recurrence (P &lt; 0.05). The pathological type of recurrent tumors was often the same as the initial tumor. Conclusion The postoperative use of ART in patients with BOT significantly increased the recurrence rate, but does not significantly affect the overall survival rate of patients. Therefore, ART in such patients should be individualized, and close follow-up is necessary after ART.

A comparative analysis of the impact of three distinct laparoscopic myomectomy techniques on ovarian reserve: a randomized clinical trial

Laparoscopic myomectomy is one of the preferred surgical treatments for symptomatic uterine fibroids. This study aimed to compare the effects of laparoscopic myomectomy with temporary uterine artery occlusion (TUAO), permanent uterine artery occlusion (PUAO), and vasopressin injection (VPI) on ovarian reserve in women with symptomatic uterine leiomyomas. This randomized clinical trial (RCT) study was conducted on women with symptomatic uterine fibroids referred to Shahid Beheshti and Al-Zahra Hospitals in Isfahan, Iran, from January 2024 to July 2024. A total of 54 women were included, with 18 women in each group. The women were randomly grouped based on the used techniques of TUAO, PUAO, and VPI. Moreover, ovarian reserve marker, including anti-Mullerian hormone (AMH) level, were measured before and after surgery. This parameter was evaluated 3 months after surgery for all patients. Also, the amount of hemoglobin was measured before and after 24 h after surgery for participants in each method. TUAO, PUAO and VPI laparoscopic myomectomy techniques had almost similar effects on ovarian reserve. The AMH level before the surgery in TUAO, PUAO, and VPI groups was reported as 3.87 ng/mL, 3.42 ng/mL, and 3.57 ng/mL, respectively. The AMH level (3 month) after the surgery was 3.78 ng/mL, 3.34 ng/mL and 3.48 ng/mL, respectively. No significant difference was reported between AMH levels among the methods before and after the surgery (P = 0.27, P = 0.12, and P = 0.29, respectively). The Hb level before the surgery in TUAO, PUAO, VPI was 11.23 g/dL, 11.55 g/dL and 11.67 g/dL, respectively. The Hb level after the surgery (24 h) was reported as 10.95 g/dL, 11.31 g/dL and 11.25 g/dL, respectively. No significant difference was reported between Hb levels among the methods before and after the surgery (P = 0.36, P = 0.31, and P = 0.13, respectively). As the choice of technique may depend on the factors such as surgeon preference and patient-specific factors, findings of this study have important implications for women undergoing LM and also highlight the need for further studies on the long-term effects of these techniques on ovarian reserve with larger sample sizes.

A nomogram of preoperative indicators predicting lymph vascular space invasion in cervical cancer

To develop predictive nomograms of lymph vascular space invasion (LVSI) in patients with early-stage cervical cancer. We identified 403 patients with cervical cancer from the Affiliated Hospital of Jiangnan University from January 2015 to December 2019. Patients were divided into the training set (n = 242) and the validation set (n = 161), with patients in the training set subdivided into LVSI (+) and LVSI (-) groups according to postoperative pathology. Preoperative hematologic indexes were compared between the two subgroups. Univariate and multivariate logistic regression analyses were used to analyze the independent risk factors for LVSI, from which a nomogram was constructed using the R package. LVSI (+) was present in 94 out of 242 patients in the training set, accompanied by a significant increase in the preoperative squamous cell carcinoma antigen (SCC), white blood cells (WBC), neutrophil (NE), platelet (PLT), neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), systemic inflammation index (SII), and tumor size (P < 0.05). Univariate analysis showed that SCC, WBC, NE, NLR, PLR, SII, and tumor size were correlated with LVSI (P < 0.05), and multivariate analysis showed that tumor size, SCC, WBC, and NLR were independent risk factors for LVSI (P < 0.05). A nomogram was correspondingly established with good performance in predicting LVSI [training: ROC-AUC = 0.845 (95% CI: 0.731-0.843) and external validation: ROC-AUC = 0.704 (95% CI: 0.683-0.835)] and high accuracy (training: C-index = 0.787; external validation: C-index = 0.759). The nomogram based on preoperative tumor size, SCC, WBC, and NLR had excellent accuracy and discriminative capability to assess the risk of LVSI in early-stage cervical cancer patients.

The impact of Germany’s human papillomavirus immunization program on HPV-related anogenital diseases: a retrospective analysis of claims data from statutory health insurances

Human papillomavirus (HPV) is the most common sexually transmitted infection, responsible for multiple HPV-related diseases, including almost all cervical cancers. The highly effective HPV vaccination has been recommended under the German HPV national immunization program (NIP) since 2007 and is reimbursed by health insurances. Vaccination uptake rates, however, remain suboptimal and data on the real-world impact of HPV vaccination in Germany are lacking. This study aims to demonstrate the population-level impact of Germany's NIP on HPV-related anogenital diseases among young women. Retrospective claims data analysis using a classic impact study design comparing disease prevalence among 28- to 33-year-old women before and after introduction of the HPV-immunization program in Germany. Claims data representing approximately two thirds of German health insurances were used. HPV-related disease outcomes included cervical cancer and high grade precancers (cervical intraepithelial neoplasia (CIN) 2+), anogenital warts, as well as vulvar, vaginal, and anal precancer/cancer. Significant declines were seen for CIN2+, anogenital warts, and vaginal precancer/cancer. Prevalence of CIN2+ declined 51.1% from 0.92% (95% CI = 0.78%, 1.08%) to 0.45% (95% CI = 0.38%, 0.53%). There was a 38.6% decline in anogenital warts prevalence from 0.44% (95% CI = 0.36%, 0.54%) to 0.27% (95% CI = 0.22%, 0.32%) and 75.0% decline in vaginal precancer/cancer prevalence from 0.04% (95% CI = 0.02%, 0.07%) to 0.01% (95% CI = 0.00%, 0.02%). The German HPV-immunization program has led to significant declines in female anogenital disease among young women in Germany, highlighting the importance of the vaccination. Moreover, the data suggest that increasing vaccination coverage in Germany could further strengthen the public-health impact of its HPV-immunization program.

Ovarian cancer management in an ESGO ovarian cancer center of excellence: a systematic case study of the interprofessional and interdisciplinary interaction

Abstract Purpose With growing knowledge about ovarian cancer over the last decades, diagnosis, evaluation and treatment of ovarian cancer patients have become highly specialized, and an individually adapted approach should be made in each woman by interdisciplinary cooperation. The present study aims to show the variety and extent of medical specialties involved at our institution according to the European Society of Gynecologic Oncology (ESGO) Quality indicators (QI). Methods A woman, diagnosed with high-grade ovarian cancer, International Federation of Gynecology and Obstetrics (FIGO) class IVb was selected for a single case observational study. The observation period (total = 22d) comprised preoperative diagnostic procedures, including imaging, the in-patient stay for cytoreductive surgery, and the postoperative course and case discussion at our interdisciplinary tumor board. Data were obtained by self-reporting and by patient file review. Results Patient tracking demonstrated an interdisciplinary cooperation of 12 medical specialties [62 physicians (63% male, 37% female)], 8 different types of nursing staff [ n  = 59 (22% male, 78% female)], and 9 different types of perioperative/administrative staff ( n  = 23; male 17,4%, female n  = 19, 82,6%). Contact with the patient was direct ( n  = 199; 76%) or without face-to-face interaction ( n  = 63; 24%). Conclusion The present study demonstrates the high diversity of physicians and the affiliated medical staff, as well as interdisciplinary intersections within teams of a specialized hospital. Matching the ESGO QIs, this report underlines the requirement of an adequate infrastructure for the complex management of advanced ovarian cancer patients. Future prospective studies are warranted to evaluate the specific procedures and actions to optimize the interprofessional and interdisciplinary workflows.

How endocervicoscopy can impact obstetric outcomes in women undergoing LEEP for CIN2 + : a retrospective cohort analysis

To assess the impact of preoperative endocervicoscopy on obstetric outcomes and complications in women undergoing LEEP for CIN2 + . This was a retrospective cohort study carried out between October 2012 and April 2018. All women had undergone cervical length measurement at T0 (before LEEP), T1 (6 months after LEEP), and T2 (at 20 weeks of pregnancy) through transvaginal ultrasound examination after LEEP for CIN2 + . A total of 528 patients fulfilled our inclusion criteria and contributed to the final analysis: 288 had undergone endocervicoscopy before the excisional procedure (Group A), while the remaining 240 (Group B) did not. Patients who did not undergo endocervicoscopy showed a greater amount of tissue excised at LEEP compared to those of Group A (6.7% vs 31.9% in Group A and B, p < 0.01, respectively). A statistically relevant difference was detected in the lesion margins involvement: negative in 93.8% in Group A compared to 65.6% in Group B. The cervicometry before the treatment resulted in similar between the two groups, while a statistically significant difference was noted after 6 months (37.5 ± 2.9 mm in Group A vs 35.1 ± 3.8 mm in Group B, p < 0.01) and at 20th week pregnancy (36.9 ± 5.3 mm in Group A vs 33.5 ± 5.6 mm in Group B, p < 0.01). The number of pregnancies after LEEP as well as the difference in the elapsed time (in months) did not result in a statistical significance between the two groups. The threatened preterm labor (TPL) and the threatened miscarriage showed a statistically significant difference in incidence between the two groups (4,2% and 4.2% in Group A vs 15.3% and 25% in Group B, p < 0.01, respectively). Endocervicoscopy reduces the size of the LEEP sample and in particular its depth, saving healthy cervical tissue, and guarantees the total eradication of the lesion as the resection margins are negative in almost all cases, allowing for a reduction of the rate of TPL and threatened miscarriage in women with CIN2 + , especially with Type 2 or 3 cervical squamocolumnar junction (SCJ).

Analysis of patients with endometrial carcinoma using the ProMise classifier: a pilot study from India

Molecular subtyping of endometrial carcinomas (EC) has been shown to classify tumors into prognostically relevant groups. Characterizing EC with a limited number of markers viz., POLE mutations, p53 mutations, and MMR status, can provide valuable information. Paraffin sections of a cohort of 48 EC from a tertiary care center were characterized for the above-mentioned molecular markers and analyzed in the context of survival. Formalin fixed paraffin embedded tissues from 48 EC were characterized for POLE mutations by Sanger sequencing (exons 9-14), for MMR (MLH1, MH2, MSH6) using immunohistochemistry (IHC) and copy number (high/low) using p53 IHC. Mutational status was integrated along with the clinicopathological details and survival analysis performed. Eleven (22.9%) patients were MMR deficient, 3 (6.3%) had POLE mutation, while 2 (4.1%) had both POLE and P53 mutations (regarded as multiple classifiers). Twelve (25%) patients were found to have P53 mutations, while the remaining 20 (41.7%) had no specific molecular profile (NSMP). Median follow-up duration was 43.5 (2-62) months with 8 recurrences and 9 deaths. Tumors with POLE mutation had the most favorable prognosis followed by the NSMP and the MMR mutated group while the P53 and multiple classifier groups had the worst prognosis in terms of OS (Log-rank p: 0.006) and PFS (Log-rank p: 0.001). The integration of molecular-clinicopathologic data for endometrial cancer classification, through cost-effective, clinically applicable assays appears to be a highly objective tool that can be adopted even in resource-limited settings. It has the potential to cause a shift in the paradigm of EC pathology and management practice.

C-section technique vs minilaparotomy after minimally invasive uterine surgery: a retrospective cohort study

Abstract Purpose Uterine leiomyomas are benign uterine tumors. The choice of surgical treatment is guided by patient's age, desire to preserve fertility or avoid "radical" surgical interventions such as hysterectomy. In laparotomy, the issue of extracting the fibroid from the cavity does not arise. However, in laparoscopy and robotic surgery, this becomes a challenge. The aim of the present study was to determine the optimal surgical approach for fibroid extraction following laparoscopic or robotic myomectomy in terms of postoperative pain, extraction time, overall surgical time, scar size, and patient satisfaction. Methods A total of 51 patients met the inclusion criteria and were considered in our analysis: 33 patients who had undergone the "ExCITE technique" (Group A), and 18 patients a minilaparotomy procedure (Group B), after either simple myomectomy, multiple myomectomy, supracervical hysterectomy, or total hysterectomy. The diagnosis of myoma was histologically confirmed in all cases. Results Regarding the postoperative pain evaluation, at 6 h, patients reported 4 [3–4] vs 6 [5.3–7] on the VAS in Group A and B, as well as at 12 h, 2 [0–2] vs 3.5 [2.3–4] in Group A and B, respectively: both differences were statistically significant (p &lt; 0.001). No statistically significant difference at 24 h from surgery was found. All patients in Group A were satisfied with the ExCITE technique, while in Group B only 67% of them. The length of the hospital stay was significantly shorter in Group A as compared to Group B (p = 0.007). In terms of the operative time for the extraction of the surgical specimen, overall operative time, and the scar size after the surgery, there was a statistically significant difference for those in Group A. Conclusion The ExCITE technique does not require specific training and allows the surgeon to offer a minimally invasive surgical option for patients, with also an aesthetic result. It is a safe and standardized approach that ensures tissue extraction without the need for mechanical morcellation.

Unraveling the challenges of intravenous leiomyomatosis: a retrospective analysis of 11 cases

Abstract Objective This study provides a concise overview of diagnostic and treatment strategies for intravenous leiomyomatosis (IVL), a rare disease with nonspecific clinical manifestations, based on cases from a tertiary referral hospital in China. Methods We retrospectively analyzed 11 premenopausal patients with confirmed IVL between 2018 and 2022. Clinical data from Ultrasound, Enhanced CT, and MRI were studied, along with surgical details, postoperative pathology, and follow-up information. Results Premenopausal patients showed no disease-specific symptoms, with 90.9% having a history of gynecological or obstetric surgery, and 72.7% having prior uterine fibroids. Cardiac involvement was evident in two cases, with echocardiography detecting abnormal floating masses from the inferior vena cava. Pelvic ultrasound indicated leiomyoma in 90.9% of cases, with ≥ 50 mm size. Surgery was the primary treatment, and lesions above the internal iliac vein resulted in significantly higher intraoperative blood loss (median 1300 ml vs. 50 ml, p  = 0.005) and longer hospital stays (median 10 days vs. 4 days, p  = 0.026). Three patients with lesions above the inferior vena cava required combined surgery with cardiac specialists. Recurrence occurred in 2 out of 11 patients with incomplete lesion resection. Conclusions IVL mainly affects premenopausal women with uterine masses, primarily in the pelvic cavity (Stage I). Pelvic ultrasound aids early screening, while Enhanced CT or MR assists in diagnosing and assessing venous lesions. Complete resection is crucial to prevent recurrence. Lesions invading the internal iliac vein and above pose higher risks during surgery. A multidisciplinary team approach is essential for patients with lesions above the inferior vena cava, with simultaneous surgery as a potential treatment option.

The impact of nutritional risk factors and sarcopenia on survival in patients treated with pelvic exenteration for recurrent gynaecological malignancy: a retrospective cohort study

Abstract Purpose The aim of the present study is to investigate the prognostic significance of nutritional risk factors and sarcopenia on the outcome of patients with recurrent gynaecological malignancies treated by pelvic exenteration. Methods We retrospectively evaluated muscle body composite measurements based on pre-operative CT scans, nutritional risk factors as assessed by a validated pre-operative questionnaire, and clinical–pathological parameters in 65 consecutive patients with recurrent gynaecological malignancies, excluding ovarian cancer, treated by pelvic exenteration at the Royal Marsden Hospital London. Predictive value for postoperative morbidity was investigated by logistic regression analyses. Relevant parameters were included in uni- and multivariate survival analyses. Results We found only (1) low muscle attenuation (MA)—an established factor for muscle depletion—and (2) moderate risk for malnutrition to be independently associated with shorter overall survival (p = 0.006 and p = 0.008, respectively). MA was significantly lower in overweight and obese patients (p = 0.04). Muscle body composite measurements were not predictive for post-operative morbidity. Conclusion The study suggests that pre-operative low MA and moderate risk for malnutrition are associated with shorter survival in patients with recurrent gynaecological malignancies treated with pelvic exenteration. Further studies are needed to validate these findings in larger cohorts.

Does a one-session sexual health education program improve sexual confidence in patients with cervical cancer? A transtheoretical model–based clinical study

This study aimed to evaluate the effects of a one-session sexual health education program using a transtheoretical model to enhance sexual self-efficacy in patients with cervical cancer. This study recruited patients with cervical cancer from the gynecological wards of a medical center in northern Taiwan. A total of 63 participants were divided into 2 groups: the control group (n = 30) received traditional sexual health education. The intervention group (n = 33) participated in a transtheoretical model (TTM)-based sexual health education program. Scores from self-report questionnaires for variables of knowledge, attitudes, and self-efficacy regarding sexual health collected 1 and 6 weeks after the intervention were compared with baseline scores. Patients who received transtheoretical model (TTM)-based sexual health education had significantly greater sexual knowledge (β = 3.794, p < 0.01), sexual attitudes (β = 9.226, p < 0.01), and sexual self-efficacy (β = 17.053, p < 0.01) than those who received traditional sexual health education at 1 and 6 weeks. Our findings suggest that a one-session sexual health education using a TTM-based model can enhance sexual knowledge, attitudes, and sexual self-efficacy among patients with cervical cancer. This educational program can be translated into routine clinical practice to help patients with cervical cancer enhance their sexual health and improve confidence in their sexual well-being.

Evaluation of circulating microRNAs as non-invasive biomarkers in the diagnosis of ovarian cancer: a case–control study

Abstract Purpose Ovarian cancer is the seventh most frequent form of malignant diseases in women worldwide and over 150,000 women die from it every year. More than 70 percent of all ovarian cancer patients are diagnosed at a late-stage disease with poor prognosis necessitating the development of sufficient screening biomarkers. MicroRNAs displayed promising potential as early diagnostics in various malignant diseases including ovarian cancer. The presented study aimed at identifying single microRNAs and microRNA combinations detecting ovarian cancer in vitro and in vivo. Methods Intracellular, extracellular and urinary microRNA expression levels of twelve microRNAs (let-7a, let-7d, miR-10a, miR-15a, miR-15b, miR-19b, miR-20a, miR-21, miR-100, miR-125b, miR-155, miR-222) were quantified performing quantitative real-time-PCR. Therefore, the three ovarian cancer cell lines SK-OV-3, OAW-42, EFO-27 as well as urine samples of ovarian cancer patients and healthy controls were analyzed. Results MiR-15a, miR-20a and miR-222 showed expression level alterations extracellularly, whereas miR-125b did intracellularly across the analyzed cell lines. MicroRNA expression alterations in single cell lines suggest subtype specificity in both compartments. Hypoxia and acidosis showed scarce effects on single miRNA expression levels only. Furthermore, we were able to demonstrate the feasibility to clearly detect the 12 miRNAs in urine samples. In urine, miR-15a was upregulated whereas let-7a was down-regulated in ovarian cancer patients. Conclusion Intracellular, extracellular and urinary microRNA expression alterations emphasize their great potential as biomarkers in liquid biopsies. Especially, miR-15a and let-7a qualify for possible circulating biomarkers in liquid biopsies of ovarian cancer patients.

Nomogram for predicting postoperative cancer-specific early death in patients with epithelial ovarian cancer based on the SEER database: a large cohort study

Abstract Purpose Ovarian cancer is a common gynecological malignant tumor. Poor prognosis is strongly associated with early death, but there is no effective tool to predict this. This study aimed to construct a nomogram for predicting cancer-specific early death in patients with ovarian cancer. Methods We used data from the Surveillance, Epidemiology, and End Results database of patients with ovarian cancer registered from 1988 to 2016. Important independent prognostic factors were determined by univariate and multivariate logistic regression and LASSO Cox regression. Several risk factors were considered in constructing the nomogram. Nomogram discrimination and calibration were evaluated using C-index, internal validation, and receiver operating characteristic (ROC) curves. Results A total of 4769 patients were included. Patients were assigned to the training set ( n  = 3340; 70%) and validation set ( n  = 1429; 30%). Based on the training set, eight variables were shown to be significant factors for early death and were incorporated in the nomogram: American Joint Committee on Cancer (AJCC) stage, residual lesion size, chemotherapy, serum CA125 level, tumor size, number of lymph nodes examined, surgery of primary site, and age. The concordance indices and ROC curves showed that the nomogram had better predictive ability than the AJCC staging system and good clinical practicability. Internal validation based on validation set showed good consistency between predicted and observed values for early death. Conclusion Compared with predictions made based on AJCC stage or residual lesion size, the nomogram could provide more robust predictions for early death in patients with ovarian cancer.

Role of integrins in the metastatic spread of high-grade serous ovarian cancer

Abstract Purpose Integrins may be involved in the metastatic spread of high-grade serous ovarian cancer (HGSOC) which determines the therapeutical approach and prognosis. We investigated the integrin expression in primary tumor and metastases of advanced HGSOC. Methods The expression of integrin α2, α4, α5, α6, and β1 was assessed by immunostaining in tumor samples of the ovary, omentum, and peritoneum of each patient. Differences in integrin expression among tumor localizations and their association with clinicopathological parameters were examined by Fisher’s exact test. The impact of integrin expression on progression-free survival (PFS) and overall survival (OS) was examined by Cox regression and Kaplan–Meier analyses. Results Hundred and thirteen tumor samples of 40 HGSOC patients were examined. The expression of the integrins did not differ between the three tumor localizations (all p values &gt; 0.05) with the exception of high expression of integrin α4 in primary tumor and omentum (52.5% versus 47.5%, p = 0.008) and primary tumor and peritoneum (52.5% versus 47.5%, p = 0.050). High expression of integrin α4 in peritoneum was associated with poorer PFS (HR 2.02 95% CI 1.01–4.05, p = 0.047), younger age (p = 0.047), and death (p = 0.046). Median PFS in patients with high expression of integrin α4 was 13.00 months, whereas median PFS in patients without high expression of integrin α4 was 21.00 months (p = 0.040). Expression of other integrins did not correlate with PFS or OS. Conclusion Expression of integrin α4 may be altered during the metastatic spread of HGSOC and affect prognosis, whereas expression of integrin α2, α5, α6, and β1 did not reveal any prognostic value.

The effect of fertility-sparing surgery on sexuality and global quality of life in women with malignant ovarian germ cell and sex cord stromal tumors: an analysis of the CORSETT database of the AGO study group

Abstract Purpose Malignant ovarian germ cell (MOGCT) and sex cord stromal tumors (SCST) are ovarian neoplasms that affect disproportionally young women. Little is known about the impact of surgical and adjuvant management of these patient’s sexual life. This study investigated the effect of fertility-sparing surgery on sexual activity and global quality of life (gQoL) in women with MOGCT and SCST. Methods CORSETT was an observational, multicenter, mixed retrospective/prospective cohort study of the AGO study group. Women of any age who had been diagnosed with MOGCTs and SCSTs between 2001 and 2011 were asked to complete the Sexual Activity Questionnaire (SAQ) and the EORTC QLQ-C30. Results In total, 355 patients were included. Of these, 152 patients with confirmed histological diagnosis had completed the questionnaires. A total of 106 patients were diagnosed with SCST and 46 with MOGCT. Totally, 83 women (55%) were sexually active. After fertility-sparing surgery, patients had a 2.6 fold higher probability for being sexually active than after non-fertility-conserving treatment (unadjusted odds ratio (OR) 2.6, p = 0.01). After adjustment for age, time since diagnosis, FIGO stage, histology and phase of disease, the OR dropped to 1.8 (p = 0.22). Of the sexually active patients, 35 (42%) reported high levels of discomfort during intercourse; 38% after fertility-sparing; and 58% after non-fertility-sparing surgery (adjusted OR 2.8, p = 0.18). Women with fertility-conserving treatment reported a significantly better global QoL (Fadj 2.1, 6.2 points difference, p = 0.03) but not more pleasure during intercourse than women without fertility-sparing surgery (Fadj 0.4, p = 0.52). Conclusion Fertility preserving approaches should be offered to every patient, when oncologically acceptable.

HiPorfin photodynamic therapy for vaginal high-grade squamous intraepithelial lesion

Abstract Purpose We aimed to evaluate the efficacy and safety of HiPorfin-photodynamic therapy (PDT) in women with vaginal high-grade squamous intraepithelial Lesion (HSIL). Methods Retrospective analysis of eighteen patients with vaginal HSIL received HiPorfin-PDT between June 2019 and May 2023. Illumination with a 630-nm laser light was applied to the lesions 48–72 h after intravenous injection of 2 mg/kg HiPorfin®. The light dose to the lesions was 150 J/cm2. Results The mean age of the 18 patients was 45.8 years (range, 24 to 63). The complete response (CR) rate was 66.7% (12/18), 83.3% (15/18) and 83.3% (15/18) at 3, 6 and 12 months after PDT, respectively. Patients who achieved CR showed no signs of recurrence during long-term follow-up. There were three cases of persistent disease showing partial response (PR) and the lesion area was significantly reduced more than 50%. One patient with persistent disease then underwent thermocoagulation one time and subsequently showed no evidence of HSIL. Pre-treatment, 100% (18/18) patients were high-risk human papilloma virus (HR-HPV)-positive. HPV eradication rate was 16.7% (3/18), 22.2% (4/18) and 44.4% (8/18) after PDT at 3, 6 and 12 months, respectively. Before treatment, liquid-based cytology test ≥ atypical squamous cells of undetermined significance (ASCUS) was 94.4% (17/18). Negative conversion ratio of cytology was 47.1% (8/17), 52.9% (9/17) and 76.5% (13/17) at 3, 6 and 12 months, respectively. There were no serious adverse effects during and after PDT. Conclusions HiPorfin-PDT may be an effective alternative treatment for vaginal HSIL for organ-saving and sexual function protection.

Efficacy of an optimal ovarian cancer screening: a best-case scenario study based on real-world data

Abstract Purpose To date, ovarian cancer screening in asymptomatic women has not shown a mortality benefit. The aim of this simulation study was to outline the impact of different histological subtypes on a potential stage-shift, achieved by screening. Methods Real-world data were derived in the period of 2000–2017 from the Klinischen Tumorregister Austria. We estimated five-year overall survival (OS) of patients with ovarian cancer regarding different histological subtypes and FIGO stages. A theoretical model was generated predicting the trend of OS mediated by an eventual down-shifting of ovarian cancer from FIGO stage III/IV to FIGO stage I/II by screening, considering the influence of different histological subtypes. Results 3458 ovarian cancer patients were subdivided according to histological subtypes and FIGO classification. Major difference in distribution of histological types was found between FIGO stage I/II and III/IV. A theoretical down-shift of tumors from high to low FIGO stages based on our registry calculations showed that the five-year OS would increase from 50% to nearly 80% by perfect screening. Conclusion In our simulation study, we showed that down-shifting ovarian cancers by successful screening might increase OS by 30 percentage point. Our results underscore the importance to recognize ovarian cancer as a heterogenous disease with distinct epidemiologic, molecular and clinical features. The individual characteristic of each histotype is of utmost impact on the definition of screening aims and may influence early detection and stage-shift. Efficacy of screening is mainly dependent on detection of high-risk cancer types and not the slow growing low-grade types.

Comparing the effects of argon plasma coagulation and interferon therapy in patients with vaginal intraepithelial neoplasia: a single-center retrospective study

Abstract Purpose This study aimed to evaluate the clinical efficacy and safety of argon plasma coagulation (APC) therapy and interferon therapy in patients with grade I and II vaginal intraepithelial neoplasia (VaIN). Methods A total of 112 patients with VaIN were diagnosed via colposcopy-induced biopsy and classified into the APC group ( n  = 77) and interferon group ( n  = 35). Clinical data including age, grade, symptoms, historical or concomitant neoplasia of the lower genital tract, indications for hysterectomy, pregnancy history, cytology, human papillomavirus (HPV) subtype, treatment modalities, and clinical outcomes were analyzed, retrospectively. Complications and clinical outcomes were assessed at 6- and 12-month follow-ups. Results There was no significant difference in the HPV clearance rate between the APC (53.42%) and interferon (33.33%) groups at 6 months after treatment. However, the 12-month follow-up of the APC group showed a significantly higher HPV clearance rate as compared to the interferon group (87.67% vs. 51.52%, P  &lt; 0.05). The APC group exhibited a significantly higher cure rate (79.22% vs. 40.0%) and lower persistence rate (12.99% vs. 37.14%) than the interferon group ( P  &lt; 0.05). Adverse reaction analysis revealed that the primary reaction in the APC group was vaginal drainage, in contrast to the increased vaginal discharge in the interferon group; though the difference was significant (68.83% vs. 28.57%, P  &lt; 0.05), no serious complications were observed. Conclusions Treatment with APC is a safe and more effective procedure against VaIN I and II, compared to interferon. APC may serve as a viable alternative to other physiotherapies.

Poly (adenosine diphosphate [ADP]–ribose) polymerase (PARP) inhibitors as maintenance therapy in women with newly diagnosed ovarian cancer: a systematic review and meta-analysis

AbstractPurposeTo investigate the efficacy and safety of poly (adenosine diphosphate [ADP]–ribose) polymerase (PARP) inhibitors (including their different types) as maintenance therapy in women with newly diagnosed ovarian cancer, and to explore whether this therapy produces a survival benefit in a subgroup population with specific clinical characteristics.MethodsWe searched MEDLINE, EMBASE, the Cochrane Library, Web of Science and relevant clinical research registry platforms on October 1, 2019, and included randomized controlled trials (RCTs) that compared PARP inhibitors with placebo in women (aged ≥ 18 years) with newly diagnosed epithelial ovarian cancer.ResultsWe identified four RCTs with 3,070 participants. Compared with placebo, PARP inhibitor maintenance therapy showed a clinically significant benefit on progression free survival (PFS) in homologous recombination deficiency (HRD) positive population (hazard ratio [HR], 0.39; 95% confidence interval [CI], 0.29–0.53). In contrast, no clear differences were identified between the groups in the HRD negative population (HR, 0.83; 95% CI 0.67–1.03). Further, there was no clear difference between the groups in terms of other outcomes (overall survival, health-related quality of life, and adverse events).ConclusionsPARP inhibitor maintenance therapy significantly prolongs the PFS of patients with newly diagnosed ovarian cancer, especially in HRD positive patients. The diagnostic test used to determine HRD status plays an important role in guiding PARP inhibitor maintenance therapy. Compared with placebo, the effect of PARP inhibitors on ovarian cancer was probably not affected by the International Federation of Gynecology and Obstetrics stage status, response to first-line chemotherapy, and residual macroscopic disease after debulking surgery.

Long noncoding RNA ZEB1-AS1 affects paclitaxel and cisplatin resistance by regulating MMP19 in epithelial ovarian cancer cells

The long noncoding RNA (lncRNA) ZEB1-AS1 is reported overexpressed in sensitive ovarian cancer cells A2780 compared with paclitaxel (PTX)-and cisplatin (DDP)- resistant. However, the function and mechanism of ZEB1-AS1 in EOC cells still unknown. We used quantitative real-time PCR (qPCR) to detect ZEB1-AS1 expression in A2780 and A2780/R cells. A combination of siRNA, plasmids, CCK8 and flow cytometry was used to detect the effect of ZEB1-AS1 on ovarian cancer cell A2780 PTX and DDP resistance. Transcriptome sequencing, qPCR, and western blot were used for further mechanistic studies. ZEB1-AS1 depletion using siRNA in chemosensitive A2780 cells significantly increased PTX and DDP resistance. In contrast, ZEB1-AS1 overexpression in PTX- and DDP-resistant A2780/resistant (A2780/R) cells reversed the observed drug resistance. Thus, ZEB1-AS1 plays an important role in PTX and DDP resistance in EOC cells. However, quantitative real-time PCR (qPCR) and western blot results suggested that ZEB1-AS1 did not regulate chemoresistance through regulation of ZEB1 protein. We used sequencing to detect mRNA expression changes in A2780 cells after ZEB1-AS1 silencing. The results indicated that MMP19 was the likely downstream factor of ZEB1-AS1. We further examined whether ZEB1-AS1 played an important role in chemoresistance by silencing MMP19 in ZEB1-AS1-overexpressing cells. CCK8 assay results suggested that MMP19 knockdown promoted ZEB1-AS1-induced chemoresistance to PTX and DDP in A2780 cells. This study is the first to reveal that ZEB1-AS1 plays a pivotal role in cancer chemoresistance.

Human papilloma virus (HPV) prevalence upon HPV vaccination in Swedish youth: a review based on our findings 2008–2018, and perspectives on cancer prevention

Abstract Purpose Three human papillomavirus (HPV) vaccines are available against up to nine HPV types. In Sweden, from 2012, Gardasil was offered to 10−12 year old girls through the school-based vaccination program, and as catchup vaccination for women up to 26 years. To obtain a baseline, and follow HPV vaccination effects, during 2008−2018, cervical and oral HPV prevalence were followed at a youth clinic in Stockholm, and in 2013 for comparison oral HPV prevalence was examined in high-school youth in a middle-sized county in Sweden. Methods In this review, we discuss all our data with cervical and oral mouthwash samples that were collected and tested for 24−27 HPV types by a bead-based multiplex assay from 2008. Results Compared with 2008−2011, with ~ 35% HPV16 and &gt; 60% high risk (HR) HPV cervical prevalence at the youth clinic, a decrease of vaccine HPV types was observed between 2013 and 2018, with e.g., HPV16 falling to 5% in catchup vaccinated women and 15−18% in nonvaccinated women. Most common cervical HR-HPV types were HPV39, 51, 52, 56, and 59 together accounting for ~ 10% of cervical cancer, and where only HPV52 is included in Gardasil-9. At baseline 2009−2011, oral HPV prevalence was ~ 10% in unvaccinated youth at the youth clinic, but after 2013 it dropped to &lt; 2% at the youth clinic and high schools. Conclusion To conclude, Gardasil HPV types have decreased, but it is still important to follow remaining HR-HPV types and cancer development, since there is an ongoing increase in the incidence of HPV-associated tonsillar and base of tongue cancer, and cervical cancer in Sweden.

Long non-coding RNA LINC00858 aggravates the oncogenic phenotypes of ovarian cancer cells through miR-134-5p/RAD18 signaling

Ovarian cancer is a common gynecological cancer. Herein, we focused on the function and probable mechanisms of LINC00858 in ovarian cancer. Real-time quantitative polymerase chain reaction (RT-qPCR) was employed for detecting the expression of LINC00858, miR-134-5p and RAD18 E3 ubiquitin protein ligase (RAD18). Cell proliferation, migration, invasion, epithelial-mesenchymal transition (EMT) and apoptosis were detected by cell counting kit-8 (CCK-8), 5-ethynyl-2'-deoxyuridine (EdU), transwell, terminal deoxynucleotidyl transferase (TdT) dUTP Nick-End Labeling (TUNEL) and western bolt experiments, as appropriate. Interplays between LINC00858, miR-134-5p and RAD18 were detected by RNA immunoprecipitation (RIP), RNA pull down and luciferase reporter assays. LINC00858 were up-regulated in ovarian cancer tissues and cells, and its expression was elevated in advanced samples compared to early ones. Knocking down LINC00858 inhibited cell proliferation, motility and EMT, but accelerated cell apoptosis in ovarian cancer. Moreover, could be sponged by LINC00858 sponged miR-134-5p to enhance RAD18 expression in ovarian cancer. Also, silenced RAD18 could also restrain oncogenic behaviors of ovarian cancer cells. Rescue experiments showed that overexpressing RAD18 reversed the effects caused by knocking down LINC00858 on cellular processes. LINC00858 sequestered miR-134-5p to elevate RAD18 expression, resulting in aggravated development of ovarian cancer. This might provide promising targets for treating patients with ovarian cancer.

Distinctive pattern of left–right asymmetry of ovarian benign teratomas in Chinese population: a 12-year-long cross-sectional study

Abstract Purpose Given the lack of research on the left–right asymmetry of ovarian teratoma among Chinese patients, this study aimed to determine the lateral distribution and related clinical characteristics of Chinese ovarian teratoma patients treated at a single center. Methods We conducted a cross-sectional study of surgical patients pathologically diagnosed with ovarian teratomas in the gynecology inpatient department of the International Peace Maternity and Child Health Hospital in Shanghai between July 2006 and July 2018. Results Of the 4417 patients with ovarian teratoma, 3835 were finally analyzed. There were 2030 (53.24%) cases of right-sided benign ovarian teratoma versus 1783 (46.76%) cases of left-sided benign teratoma (P &lt; 0.001). The recurrence rate of benign ovarian teratoma was 4.2%; recurrence occurred more often on the left side (left vs. right = 55 vs. 45%, P = 0.033). Compared with the right-sided ovarian teratoma patients, left-sided ones had significantly high recurrence risk (OR 1.430; 95% CI 1.03–1.99). The rate of ovarian torsion in patients with ovarian mature cystic teratomas (MCTs) during intrauterine pregnancy was 3.17 versus 1.72% in non-pregnant MCT patients (P = 0.049). For those MCT patients with intrauterine pregnancy, ovarian torsion occurs more often on the right side (left vs. right = 16.67 vs. 83.33%, P = 0.028). Conclusion This study confirms a distinctive right-side dominance of benign ovarian teratomas. Compared with the right side, recurrent ovarian teratomas occur more often on the left side, requiring close follow-up. Intrauterine pregnancy may increase the risk of ovarian torsion, particularly on the right side, in MCT patients.

Effect of macrophages on biological function of ovarian cancer cells in tumor microenvironment in vitro

To investigate the influence of two types of tumor-associated macrophages (TAMs) on the biological function of human ovarian cell lines in vitro. (1) M2 macrophage release was induced by IL-4, and M1 macrophage release by phorbol myristate acetate (PMA) in vitro. Flow cytometry was used to distinguish these two types; (2) transwell culture system was used to establish a non-contact co-culture model of macrophage and ovarian cancer cells (SKOV3, HEY, HO8910 and A2780) in vitro. The microenvironment of ovarian cancer was simulated in vitro. (3) The proliferation, apoptosis, migration and invasion of ovarian cancer cells SKOV3, HEY, HO8910 and A2780 were analyzed after co-culture. Their proliferation was detected by CCK8 method, apoptosis by flow cytometry, Annexin V-FITC/PI double staining, invasion by Transwell assay, and migration by wound healing test. (1) IL-4-induced macrophages (M2) overexpressed CD163, and PMA-induced macrophages (M1) overexpressed HLA-DR. After co-culturing primary macrophages with ovarian cancer cells (SKOV3, HEY, HO8910, A2780), macrophage CD163 was highly expressed. (2) Proliferation and apoptosis of ovarian cancer cells (SKOV3, HEY, HO8910, A2780): the proliferation of ovarian cancer cells in M2 co-culture group increased compared to that in M1 co-culture group and primary co-culture group (p < 0.05); the apoptosis of ovarian cancer cells in M2 co-culture group decreased compared to that in M1 co-culture group and primary co-culture group (p < 0.05). (3) Migration and invasion of ovarian cancer cells (SKOV3, HEY, HO8910, A2780): the invasion of ovarian cancer cells in M2 co-culture group increased compared to that in M1 co-culture group and primary co-culture group (p < 0.05); the migration of ovarian cancer cells in M2 co-culture group increased compared to that in M1 co-culture group and the primary co-culture group (p < 0.05). In the simulated in vitro tumor microenvironment, co-cultured ovarian cancer cells polarized macrophages to the M2 phenotype. Furthermore, M2 macrophages enhanced the proliferation, invasion and migration, and inhibited the apoptosis of ovarian cancer cells.

Unilateral cystectomy and serous histology are associated with relapse in borderline ovarian tumor patients with fertility-sparing surgery: a systematic review and meta-analysis

Surgical procedures, histological subtypes, and surgical approaches are involved in the recurrence of borderline ovarian tumors (BOTs), but whether those three factors affect relapse remains controversial. This study aimed to explore the effects of surgical procedures, histological subtypes, and surgical approaches on the relapse and pregnancy rates of BOT after fertility-preserving surgery (FPS) according to the patients' characteristics. A systematic search of PubMed, Embase, and the Cochrane library was conducted from their inception to November 2018. Studies that investigated the impact of surgical procedures, histological subtypes, and surgical approaches on the relapse and pregnancy rates in patients with BOT after FPS were eligible. The pooled odds ratios (ORs) with the corresponding 95% confidence intervals (CIs) were calculated using the random-effects model. Thirty-five studies involving a total of 2921 patients with BOT after FPS were included. The pooled ORs indicated that the risk of relapse was significantly increased in patients who underwent unilateral cystectomy or with serous BOT. There was no significant difference between laparoscopy and laparotomy on the risk of relapse. Surgical procedures, histological subtypes, and surgical approaches did not influence pregnancy rates. Patients who underwent unilateral cystectomy or with serous BOT presented an excess risk of relapse after FPS, but the surgical approach did not affect the risk of relapse. The pregnancy rate is not affected by surgical procedures, histological subtypes, and surgical approaches.

Influence of interdisciplinary frailty screening on perioperative complication rates in elderly ovarian cancer patients: results of a retrospective observational study

Abstract Purpose Frailty is a frequent and underdiagnosed multidimensional age-related syndrome, involving decreased physiological performance reserves and marked vulnerability against major stressors. To standardize the preoperative frailty assessment and identify patients at risk of adverse surgical outcomes, commonly used global health assessment tools were evaluated. We aimed to assess three interdisciplinary preoperative screening assessments to investigate the influence of frailty status with in-hospital complications irrespective of surgical complexity and radicality in older women with ovarian cancer (OC). Methods Preoperative frailty status was examined by the G8 geriatric screening tool (G8 Score-geriatric screening), Eastern Cooperative Oncology Group performance status (ECOG PS-oncological screening), and American Society of Anesthesiologists Physical Status System (ASA PS-anesthesiologic screening). The main outcome measures were the relationship between perioperative laboratory results, intraoperative surgical parameters and the incidence of immediate postoperative in-hospital complications with the preoperative frailty status. Results 116 consecutive women 60 years and older (BMI 24.8 ± 5.2 kg/m2) with OC, who underwent elective oncological surgery in University Medical Center Mainz between 2008 and 2019 were preoperatively classified with the selected global health assessment tools as frail or non-frail. The rate of preoperative anemia (hemoglobin ≤ 12 g/dl) and perioperative transfusions were significantly higher in the G8-frail group (65.9% vs. 34.1%; p = 0.006 and 62.7% vs. 41.8%, p = 0.031; respectively). In addition, patients preoperatively classified as G8-frail exhibited significantly more postoperative clinical in-hospital complications (27.8% vs. 12.5%, p = 0.045) independent of chronological age and BMI. In contrast, ECOG PS and ASA PS did not predict the rates of postoperative complications (all p values &gt; 0.05). After propensity score matching, the complication rate in the G8-frail cohort was approximately 1.7 times more common than in the G8-non-frail cohort. Conclusion Preoperative frailty assessment with the G8 Score identified elderly women with OC recording a significantly higher rate of postoperative in-hospital complications. In G8-frail patients, preoperative anemia and perioperative transfusions were significantly more recorded, regardless of chronological age, abnormal BMI and surgical complexity. Standardized preoperative frailty assessment should be added to clinical routine care to enhance risk stratification in older cancer individuals for surgical patient-centered decision-making.

Intergroup-statement: statement of the german ovarian cancer commission, the North-Eastern German Society of gynecological Oncology (NOGGO), AGO Austria and AGO Swiss regarding the use of homologous repair deficiency (HRD) assays in advanced ovarian cancer

Abstract Introduction Homologous recombination deficiency (HRD) is a key biomarker in the management of high-grade serous ovarian cancer (HGSOC), guiding treatment decisions, particularly regarding the use of poly(ADP-ribose) polymerase inhibitors (PARPi). As multiple HRD assays are available, each with distinct methodologies and cutoff values, the interpretation and clinical application of HRD testing remain complex. This intergroup statement, endorsed by the German Ovarian Cancer Commission, NOGGO, AGO Austria, and AGO Swiss, aims to provide guidance on the indications, appropriate use, and limitations of HRD testing in ovarian cancer. Materials and methods The statement is based on an interdisciplinary review of available literature, clinical trial data, and expert consensus. The recommendations focus on the current landscape of HRD assays, their clinical applicability, and practical considerations regarding the optimal timing and indications for testing. Results and discussion Various HRD assays, including established commercial tests and emerging academic-clinical approaches, are reviewed in this statement. The document outlines key eligibility criteria for HRD testing in ovarian cancer, emphasizing its relevance in specific histological subtypes and clinical scenarios. Additionally, exclusion criteria are defined, highlighting cases where HRD testing may not be appropriate due to insufficient clinical validation or lack of therapeutic implications. Finally, the statement discusses the pathological minimum requirements for tissue samples used in HRD testing, ensuring adequate sample quality and tumor content for reliable results. Conclusion HRD testing is a valuable tool for personalizing ovarian cancer treatment, particularly in identifying patients who may benefit from PARPi therapy. However, assay selection, timing, and result interpretation require careful consideration. This statement provides a structured approach to optimize HRD testing, aiming to improve clinical decision-making and patient outcomes.

Anti-NMDA receptor encephalitis associated with ovarian tumor: the gynecologist point of view

Anti-NMDA receptor antibody (anti-NMDAr) encephalitis, although still a rare condition, is well known to neurologists as it is the leading cause of non-infectious acute encephalitis in young women. However, this is less well known to gynecologists, who may have a decisive role in etiological management. Indeed, in 30-60% of cases in women of childbearing age, it is associated with the presence of an ovarian teratoma, whose removal is crucial in the resolution of symptomatology. Primary objective of our work was to present a review in a very schematic and practical way for gynecologists, about the data on anti-NMDAr encephalitis in terms of epidemiology, clinical symptomatology, treatment and prognosis. The second objective was to propose a decision tree for gynecologists to guide them, in collaboration with neurologists and anesthesiologists, after the diagnosis of NMDAr encephalitis associated with an ovarian mass. We conducted an exhaustive review of existing data using PubMed and The Cochrane Library. Then, we illustrated this topic by presenting two typical cases from our experience. Anti-NMDA antibody encephalitis association with an ovarian teratoma is common, especially in women of reproductive age. Complementary examinations in search of an ovarian teratoma must therefore be systematic to envisage a possible surgical excision that may improve patient prognosis. Anti-NMDA antibody encephalitis should not be ignored by gynecologists whose role in management is central.

Ovarian Sertoli-Leydig cell tumors: an analysis of 13 cases

To report the clinical, ultrasound and histopathological characteristics, clinical management, and prognosis of 13 patients with Sertoli-Leydig cell tumors (SLCTs) of ovary. 13 patients with pathologically confirmed ovarian SLCTs at International Peace Maternity and Child Health Hospital from 2010 and 2019 were included in this study. The clinical, ultrasound and histopathological characteristics, clinical management, and prognosis of 13 patients were retrospectively analyzed. The age ranged 25-68 years. Of the 8 (62%) patients presenting endocrine symptoms, 4 had post-menopausal hemorrhage, 4 had menstrual irregularity, 2 had androgenic manifestations, 1 had hirsutism, and 1 showed acne with thyroid nodules. 1 patient had elevated cancer antigen 125 (CA125), and 2 had elevated testosterone (T). The other 5 patients showed no symptoms of whom masses were detected incidentally by physical examination. All tumors were at stage I and confined to unilateral ovary. 11 tumors were solid or mixed solid-cystic masses with clear boundaries on ultrasound, and 1 tumor was a cystic mass. 7 tumors were intermediately differentiated and 6 were poorly differentiated, among which 1 case had heterologous elements (poorly differentiated) and 8 had a retiform pattern. Grade 2 endometrial cancer occurred in 2 cases (1 intermediately differentiated and 1 poorly differentiated). One case had multinodular goiter (intermediately differentiated). The patients were classified into endocrine function group (8/13) and no endocrine function (5/13). The proportion of retiform pattern of the group with endocrine function was significantly higher than that of no endocrine function group (p < 0.05). However, the mean age, diameter of tumors, and the proportions of poor differentiation and rupture showed no significant difference. All patients were treated with surgical excision. Three cases underwent surgery twice after the pathological results came out. For the final surgery, 1 patient underwent cystectomy, 3 underwent unilateral salpingo-oophorectomy, and 9 underwent total hysterectomy and bilateral salpingo-oophorectomy. 7 had received postoperative chemotherapy. All of 13 patients exhibited disease-free survival (DFS) with the longest follow-up time being 9 years. The clinical characteristics and imaging findings may provide information for the diagnosis of SLCTs. Higher percentage of retiform pattern was found in endocrine function group. Concurrence of Grade 2 endometrial carcinoma with SCLTs was reported. The prognosis of SLCTs is good. Conservative surgery is acceptable for young patients wishing to preserve fertility.

Does lymph node ratio have any prognostic significance in maximally cytoreduced node-positive low-grade serous ovarian carcinoma?

To determine the prognostic impact of the lymph node ratio (LNR) in node-positive low-grade serous ovarian cancer (LGSOC). We retrospectively reviewed women with LGSOC who had undergone maximal cytoreduction followed by standard chemotherapy in 11 centers from Turkey during a study period of 20 years. Sixty two women with node-positive LGSOC were identified. LNR was defined as the number of metastatic lymph nodes (LNs) divided by the number of total LNs removed. We grouped patients pursuant to the LNR as LNR ≤ 0.09 and LNR > 0.09. The prognostic value of LNR was investigated by employing the univariate log-rank test and multivariate Cox-regression model. With a median follow-up of 45 months, the 5-year progression-free survival (PFS) rates were 61.7% for women with LNR ≤ 0.09 and 32.0% for those with LNR > 0.09 (p = 0.046) whereas, the 5-year overall survival (OS) rates were 72.8% for LNR ≤ 0.09 and 54.7% for LNR > 0.09 (p = 0.043). On multivariate analyses, lymphovascular space invasion (LVSI) (Hazard Ratio [HR] 4.18, 95% confidence interval [CI] 1.88-9.27; p  0.09 (HR 3.51, 95% CI 1.54-8.03; p = 0.003) were adverse prognostic factors for PFS. Additionally, LVSI (HR 6.56, 95% CI 2.33-18.41; p  0.09 (HR 7.20, 95% CI 2.33-22.26; p = 0.001) were independent prognostic factors for decreased OS. LNR > 0.09 seems to be an independent prognosticator for decreased survival outcomes in LGSOC patients who received maximal cytoreduction followed by standard adjuvant chemotherapy.

Incidence and predictors for chemotherapy modifications and their impact on the outcome of ovarian cancer patients

Abstract Purpose Chemotherapy (CTX) is an important part of the treatment strategy of stage II–IV ovarian cancer. CTX modifications, such as delays, dose reductions or premature terminations might have a negative impact on overall survival (OS) and progression free survival (PFS). The goal of this study was to determine the incidence and predictors of CTX modifications and their influence on survival. Methods An observational retrospective cohort analysis of 192 ovarian cancer patients who were treated at the Department of Obstetrics and Gynaecology, Technical University Munich, Germany, according to international guidelines was performed including from 2009 to 2013. A potential association between patient and disease characteristics and CTX modifications was tested with multivariate logistic regression. OS and PFS were estimated by Kaplan–Meier analysis. Results 44.8% (86/192) received a modification of CTX. 34 (17.7%) women discontinued CTX prematurely, 17 (8.9%) underwent a dose reduction, 16 (8.3%) experienced a CTX delay and 10 (5.2%) had both a delay and a dose modification. In nine (4.7%) patients, the dose needed to be divided. Leukopenia (p &lt; 0.001) and anaemia (p = 0.003) were significantly more common in patients with CTX modifications. Significant predictors for CTX modifications were a history of thrombosis or embolism (p &lt; 0.001) and residual tumour postoperatively (p = 0.003). Patients with CTX modifications showed a significantly lower OS as well as PFS (p &lt; 0.001), even after adjustment for prognostic factors such as age, body-mass-index, residual tumour, histology, FIGO stage and grading (p = 0.005 for OS and p = 0.001 for PFS). Conclusion CTX modifications have a negative impact on survival. Significant predictors for such modifications are a history of thrombosis or embolism and the presence of residual postoperative tumour. Further studies are needed to avoid CTX modifications and to improve survival of ovarian cancer patients.

Interdisciplinary risk counseling for hereditary breast and ovarian cancer: real-world data from a specialized center

Abstract Purpose Hereditary breast and ovarian cancer has long been established to affect a considerable number of patients and their families. By identifying those at risk ideally before they have been diagnosed with breast and/or ovarian cancer, access to preventive measures, intensified screening and special therapeutic options can be obtained, and thus, prognosis can be altered beneficially. Therefore, a standardized screening and counseling process has been established in Germany under the aegis of the German Consortium for Hereditary Breast and Ovarian Cancer (GC-HBOC). As one of these specialized clinics, the HBOC-Center at Charité offers genetic counseling as well as genetic analysis based on the GC-HBOC standards. This analysis aims first at depicting this process from screening through counseling to genetic analysis as well as the patient collective and second at correlating the results of genetic analysis performed. Thus, real-world data from an HBOC-Center with a substantial patient collective and a high frequency of pathogenic variants in various genes shall be presented. Methods The data of 2531 people having been counseled at the HBOC-Center at Charité in 2016 and 2017 were analyzed in terms of patient and family history as well as pathogenic variants detected during genetic analysis with the TruRisk® gene panel when genetic analysis was conducted. This standardized analysis is compiled and regularly adjusted by the GC-HBOC. The following genes were included at time of research: BRCA1, BRCA2, ATM, CDH1, CHEK2, PALB2, RAD51C, RAD51D, NBN, and TP53. Results Genetic analysis was conducted in 59.8% of all cases meeting the criteria for genetic analysis and 286 pathogenic variants were detected among 278 (30.3%) counselees tested using the TruRisk® gene panel. These were primarily found in the genes BRCA1 (44.8%) and BRCA2 (28.3%) but also in CHEK2 (12.2%), ATM (5.6%) and PALB2 (3.5%). The highest prevalence of pathogenic variants was seen among the families with both ovarian and breast cancer (50.5%), followed by families with ovarian cancer only (43.2%) and families with breast cancer only (35.6%)—these differences are statistically significant (p &lt; 0.001). Considering breast cancer subtypes, the highest rate of pathogenic variants was detected among patients with triple-negative breast cancer (40.7%) and among patients who had had been diagnosed with triple-negative breast cancer before the age of 40 (53.4%)—both observations proved to be statistically significant (p = 0.003 and p = 0.001). Conclusion Genetic counseling and analysis provide the foundation in the prevention and therapy of hereditary breast and ovarian cancer. The rate of pathogenic variants detected is associated with family history as well as breast cancer subtype and age at diagnosis, and can reach considerable dimensions. Therefore, a standardized process of identification, genetic counseling and genetic analysis deems mandatory.

Prognostic role of thrombocytosis in recurrent ovarian cancer: a pooled analysis of the AGO Study Group

Although thrombocytosis in patients with primary ovarian cancer has been widely investigated, there are only very few data about the role of thrombocytosis in recurrent ovarian cancer. The aim of our study was to investigate the impact of pretreatment thrombocytosis prior to chemotherapy on clinical outcome in patients with recurrent platinum eligible ovarian cancer. In our retrospective analysis we included 300 patients who were treated by AGO Study Group Centers within three prospective, randomized phase-III-trials. All patients included had been treatment-free for at least 6 months after platinum-based chemotherapy. We excluded patients who underwent secondary cytoreductive surgery before randomization to the trial. Thrombocytosis was defined as a platelet count of ≥ 400⋅10 Pretreatment thrombocytosis was present in 37 out of 300 (12.3%) patients. Patients with thrombocytosis responded statistically significantly less to chemotherapy (overall response rate 35.3% and 41.6%, P = 0.046). The median progression-free survival (PFS) for patients with thrombocytosis was 6.36 months compared to 9.00 months for patients without thrombocytosis (hazard ratio [HR] = 1.19, 95% confidence interval [CI] = 0.84-1.69, P = 0.336). Median overall survival (OS) of patients with thrombocytosis was 16.33 months compared to 23.92 months of patients with a normal platelet count (HR = 1.46, 95% CI = 1.00-2.14, P = 0.047). The present analysis suggests that pretreatment thrombocytosis is associated with unfavorable outcome with regard to response to chemotherapy and overall survival in recurrent ovarian cancer.

Significance of lymph node ratio on survival of women with borderline ovarian tumors

To assess the qualitative and quantitative measures of the effect of pelvic lymph node involvement on survival of women with borderline ovarian tumors (BOTs). This is a retrospective study examining the Surveillance, Epidemiology, and End Results Program between 1988 and 2003. Women with stage T1-3 BOTs who had results of pelvic lymph node status at surgery were included. The effect of lymph node involvement on cause-specific survival (CSS) was evaluated using multivariable analysis with the following approaches: (1) any involvement, (2) involvement of multiple nodes (≥ 2 nodes), and (3) lymph node ratio (LNR), defined as the ratio of the number of tumor-containing lymph nodes to the total number of harvested lymph nodes. A total of 1524 women were examined for analysis. Median count of sampled nodes was 8 (interquartile range 3-15), and there were 81 (5.3%, 95% confidence interval [CI] 4.2-6.4) women who had lymph node involvement. Median follow-up was 15.8 (interquartile range 13.8-18.9) years, and 83 (5.4%) women died of BOTs. After controlling for age, histology, stage, and tumor size, only LNR remained an independent prognostic factor for decreased CSS (adjusted hazard ratio [HR] per percentage unit 1.015, 95% CI 1.003-1.026, P = 0.014), whereas any involvement (adjusted HR 1.700, 95% CI 0.843-3.430, P = 0.138) and involvement of multiple nodes (adjusted HR 1.644, 95% CI 0.707-3.823, P = 0.249) did not. On cutoff analysis, LNR ≥ 13% had the largest magnitude of significance on multivariable analysis of CSS (adjusted HR 2.399, 95% CI 1.163-4.947, P = 0.018). Our study suggests that high pelvic LNR may be a prognostic factor associated with decreased CSS in women with BOTs.

Temporal trends of subsequent breast cancer among women with ovarian cancer: a population-based study

To examine trends, characteristics and outcomes of women who develop both ovarian and breast cancers. This is a retrospective study examining the Surveillance, Epidemiology, and End Results Program from 1973 to 2013. Among ovarian cancer (n = 133,149) and breast cancer (n = 1,143,219) cohorts, women with both diagnoses were identified and temporal trends, tumor characteristics and survival were examined. There were 6446 women with both malignancies, representing 4.8% of the ovarian cancer cohort and 0.6% of the breast cancer cohort. Women with ovarian cancer who had secondary breast cancer were younger than those without secondary breast cancer early in the study period (52.3 versus 59.2 in 1973) but older in more recent years (68.5 versus 62.1 in 2013, P < 0.001). The number of breast cancer survivors who developed postcedent ovarian cancer decreased from 1.5 to 0.2% from 1979 to 2008 (relative risk reduction 90.0%, P < 0.05). Similarly, the number of ovarian cancer survivors who developed postcedent breast cancer decreased from 7.2 to 2.0% from 1973 to 2008 (relative risk reduction 72.4%, P < 0.05). Tumor characteristics were more likely to be favorable in women with ovarian cancer who developed postcedent breast cancer but unfavorable in those who had antecedent breast cancer (all, P < 0.05). Women with ovarian cancer who had secondary breast cancer had superior cause-specific survival compared to those who did not develop breast cancer regardless of breast cancer timing (P < 0.05). Our study demonstrated that the demographics of women who develop breast cancer and ovarian cancer have changed over time and diagnosis of secondary breast cancer after ovarian cancer has decreased.

Outcomes and prognostic factors of patients with recurrent and persistent malignant ovarian germ cell tumors

Due to the rarity of recurrent and persistent malignant ovarian germ cell tumors (MOGCTs), there is no standardized protocol for salvage therapy. This study aimed to investigate the outcomes and prognostic factors of patients with recurrent and persistent MOGCTs. Clinical data for 59 patients with recurrent and persistent MOGCTs admitted to Peking Union Medical College Hospital from January 1, 2000, to April 30, 2018, were retrospectively analyzed. Twenty-one cases (35.6%) were recurrent, and 38 (64.4%) were persistent. Patient age ranged from 1 to 39 years, and disease stage was as follows: 33 stage I, 4 stage II, 21 stage III, and 1 stage IV. There were 19 immature teratomas, 26 yolk sac tumors, 1 dysgerminoma, and 13 mixed germ cell tumors. Regarding the primary surgery, fertility was preserved in 49 patients and not preserved in 10 patients. Among the patients who underwent fertility-preserving primary surgery, 40 had fertility preserved in the second operation, and 9 did not. In the mean follow-up of 52.6 months (range 2-279 months) after recurrence, 19 patients (32.2%) experienced a second relapse, and 16 (27.1%) died. The 5-year survival and progression-free survival rates after relapse were 70.0% and 67.0%, respectively. The optimal salvage surgery and chemotherapy regimen after relapse were independent prognostic factors (P < 0.05). The prognosis of recurrent and persistent MOGCTs was good after salvage therapy. The optimal salvage surgery and adjuvant standardized chemotherapy significantly impact patient prognosis. For young nulliparous patients, secondary fertility-sparing salvage therapy can be considered.

Ovarian cancer stem cells: ready for prime time?

The role of cancer stem cells (CSC) remains controversial and increasingly subject of investigation as a potential oncogenetic platform with promising therapeutic implications. Understanding the role of CSCs in a highly heterogeneous disease like epithelial ovarian cancer (EOC) may potentially lead to the better understanding of the oncogenetic and metastatic pathways of the disease, but also to develop novel strategies against its progression and platinum resistance. We have performed a review of all relevant literature that addresses the oncogenetic potential of stem cells in EOC, their mechanisms, and the associated therapeutic targets. Cancer stem cells (CSCs) have been reported to be implicated not only in the development and pathways of intratumoral heterogeneity (ITH), but also potentially modulating the tumor microenvironment, leading to the selection of sub-clones resistant to chemotherapy. Furthermore, it appears that the enhanced DNA repair abilities of CSCs are connected with their endurance and resistance maintaining their genomic integrity during novel targeted treatments such as PARP inhibitors, allowing them to survive and causing disease relapse functioning as a tumor seeds. It appears that CSCs play a major role in the underlying mechanisms of oncogenesis and development of relapse in EOC. Part of promising future plans would be to not only use them as therapeutic targets, but also extent their value on a preventative level through engineering mechanisms and prevention of EOC in its origin.

Clinicopathological factors and prognosis analysis of 39 cases of non-gestational ovarian choriocarcinoma

Non-gestational ovarian choriocarcinoma (NGOC) is a rare malignant germ cell tumor. Through literature review and cases collection, we aim to analyze prognostic factors for NGOC and summarize its clinicopathological characteristics to guide the individualized treatment. We searched PubMed database, Cochrane library, and Google Scholar for cases published between January 1, 1967 and July 31, 2018 using various search terms. We retrieved patients' clinicopathological characteristics, treatment, and prognosis information from included studies. These patients were divided into two groups: died (case group) or alive (control group) group. We summarized and compared their clinical (age, symptoms, R0 resection, serum HCG levels, chemotherapy regimen) and pathological (pure vs non-pure type, tumor size, tumor location, metastasis sites, stage) features by statistical analysis. Only 39 patients were retrieved from 36 studies in total. The median age was 30 years (range 12- to 65-years old). The peak incidence was in the adolescent age 12-25 years. Median follow-up was 20.3 months (range 1-84 months). 9 (23%) patients died; 24 (62%) patients were alive; 6 (15%) were lost to follow-up. Upon univariate analysis, we found age had a poor impact on overall survival (OS) in NGOC, HR - 0.057, 95% CI - 0.111 to - 0.004. Pure type NGOC has a better OS than mixed type, HR - 2.621, 95% CI - 4.577 to - 0.666. R0 resection is a good prognostic factor for OS, HR 2.967, 95% CI 0.709-5.224. Clinicians should try to achieve R0 resection to improve the prognosis for NGOC patients even among advanced patients.

Diagnostic and prognostic role of TFF3, Romo-1, NF-кB and SFRP4 as biomarkers for endometrial and ovarian cancers: a prospective observational translational study

Abstract Purpose This study aimed to evaluate trefoil factor 3 (TFF3), secreted frizzled-related protein 4 (sFRP4), reactive oxygen species modulator 1 (Romo1) and nuclear factor kappa B (NF-κB) as diagnostic and prognostic markers of endometrial cancer (EC) and ovarian cancer (OC). Methods Thirty-one patients with EC and 30 patients with OC undergone surgical treatment were enrolled together with 30 healthy controls in a prospective study. Commercial ELISA kits determined serum TFF-3, Romo-1, NF-кB and sFRP-4 concentrations. Results Serum TFF-3, Romo-1 and NF-кB levels were significantly higher in patients with EC and OC than those without cancer. Regarding EC, none of the serum biomarkers differs significantly between endometrial and non-endometrioid endometrial carcinomas. Mean serum TFF-3 and NF-кB levels were significantly higher in advanced stages. Increased serum levels of TFF-3 and NF-кB were found in those with a higher grade of the disease. Regarding OC, none of the serum biomarkers differed significantly among histological subtypes. Significantly increased serum levels of NF-кB were observed in patients with advanced-stage OC than those with stage I and II diseases. No difference in serum biomarker levels was found between those who had a recurrence and those who had not. The sensibility and specificity of these four biomarkers in discriminating EC and OC from the control group showed encouraging values, although no one reached 70%. Conclusions TFF-3, Romo-1, NF-кB and SFRP4 could represent new diagnostic and prognostic markers for OC and EC. Further studies are needed to validate our results.

Friend or foe? The prognostic role of endometriosis in women with clear cell ovarian carcinoma. A UK population-based cohort study

The prognostic role of endometriosis amongst women with ovarian clear cell carcinoma (OCCC) remains debatable. The aim of this study was to ascertain the effect of endometriosis on the prognosis of OCCC. A retrospective review of the medical records of 94 women diagnosed and treated for OCCC at a tertiary gynaecological cancer centre in the UK, spanning the period 2010-2019. Women were divided into two groups according to the presence of endometriosis. Clinico-pathological characteristics, progression-free survival (PFS) and overall survival (OS) were collated between the two groups. Forty-six cases of endometriosis-free OCCC (Ef-OCCC) were collated with 48 cases of endometriosis-related OCCC (Er-OCCC). There was no significant difference between the two groups regarding age (p-value = 0.2), FIGO stage (p-value = 0.8), residual disease (RD) (p-value = 0.07), adjuvant chemotherapy agent (p-value = 0.4) or chemo-resistance (p-value = 0.9). The presence of endometriosis did not significantly affect either OS or PFS. The median OS in the Ef-OCCC and Er-OCCC was 55.00 (95% CI 32.00-189.00) and 71.00 (95% CI 47.00-97.00; log rank = 1.35, p-value = 0.2) months. The median PFS in the Ef-OCCC and Er-OCCC group was 39.00 (95% CI 19.00-143.00) and 39.00 (95% CI 19.00-62.00; log rank = 0.7, p-value = 0.4) months. Survival differences between the two groups were not significant after stratification analysis for independent prognosticators. Endometriosis was not independently associated with the prognosis of OCCC either in crude analysis or after stratification for stage and RD. Further larger, well-designed prospective studies are warranted to draw firmer conclusions on the intrinsic link between endometriosis and OCCC.

Depression and anxiety in women with malignant ovarian germ cell (MOGCT) and sex cord stromal tumors (SCST): an analysis of the AGO-CORSETT database

Abstract Introduction The intention of this study was to evaluate the level of anxiety and depression of malignant ovarian germ cell (MOGCT) and sex cord stromal tumors (SCST) survivors and to identify possible alterable cofactors. Methods CORSETT was an observational, multicenter, mixed retrospective/prospective cohort study of the AGO Studygroup. Women who had been diagnosed with MOGCTs and SCSTs between 2001 and 2011 were asked to complete the Hospital Anxiety and Depression Scale (HADS) to evaluate distress. Predictors of distress (type of surgery, chemotherapy, time since diagnosis, recurrence, second tumor, pain) were investigated using multivariate linear regression analysis. Results 150 MOGCT and SCST patients with confirmed histological diagnosis completed the questionnaire median seven years after diagnosis. They had a HADS total score ≥ 13 indicating severe mental distress in 34% of cases. Patients after fertility-conserving surgery had lower probability of severe mental distress than those without fertility-conserving treatment (β = − 3.1, p = 0.04). Pain was associated with the level of distress in uni- and multivariate analysis (coef 0.1, p &lt; 0.01, coef. Beta 0.5). Discussion Severe mental distress was frequent in patients with MOGCT and SCST and the level of pain was associated with the level of distress. Fertility conserving therapy, however, was associated with less mental distress. Screening and treatment of pain and depression is required to improve mental well-being in survivors of MOGCT and SCST.

Associations of preoperative serum high-density lipoprotein cholesterol and low-density lipoprotein cholesterol levels with the prognosis of ovarian cancer

The effect of serum lipids on ovarian cancer is controversial. We conducted this study to evaluate the prognostic value of preoperative plasma lipid profile in patients with ovarian cancer. The medical records of 156 epithelial ovarian cancer patients who underwent surgical resection in our department were retrospectively reviewed and analyzed. Serum lipids profiles, including total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), triglyceride (TG), apolipoprotein A-I (apoA-I), apolipoprotein B (apoB) and clinicopathologic data, were analyzed. Cox proportional hazards regression analyses and Kaplan-Meier method were performed to evaluate the overall survival (OS) and progression-free survival (PFS). Multivariable Cox regression analysis found that preoperative higher LDL-C level was significantly associated with worse OS (HR 2.088, 95% CI 1.052-4.147, p = 0.035), whereas higher HDL-C level showed significant association with better PFS (HR 0.491, 95% CI 0.247-0.975, p = 0.042). Further Kaplan-Meier survival analysis demonstrated that OS was longer for patients with low levels of LDL-C (< 2.76 mmol/L) compared to those with high levels of LDL-C (≥ 2.76 mmol/L) (P = 0.028), and PFS was better for patients with high levels of HDL-C (≥ 1.19 mmol/L) compared to those with low levels of HDL-C (< 1.19 mmol/L) (P = 0.001). Preoperative HDL-C and LDL-C levels are significant predictors of clinical outcome in patients with epithelial ovarian cancer.

Feasibility of a large multi-center translational research project for newly diagnosed breast and ovarian cancer patients with affiliated biobank: the BRandO biology and outcome (BiO)-project

Large translational research projects may contribute to further progress in cancer treatment by exploring molecular biology, immunologic approaches and identification of new prognostic and predictive factors. Therefore, the BRandOBio-project combines a clinical registry for collection of patient and tumor characteristics with a biobank comprising tumor and liquid biopsies. In addition, sociodemographic, environmental and lifestyle factors of included patients with primary newly diagnosed breast or ovarian cancer, other rare malignant ovarian tumors or gestational trophoblastic disease are prospectively collected. The target population includes the German "Alb-Allgäu-Bodensee Region" which constitutes the outreach area of the University Hospital Ulm with affiliated academic centers and private practices. Clinical data combined with primary tumor tissue samples and longitudinal repeatedly collected blood samples [before, 6 (in high-risk situations), 12, 36 and 60 months after treatment and at relapse] will be acquired from more than 4000 patients within the next years. Standardized questionnaires are given to patients of the University Hospital Ulm and eight selected external sites for assessing life style and cancer risk factors. Concomitantly, storage of paraffin-embedded tumor samples as well as liquid biopsy samples will allow translational research projects, for example in terms of investigating circulating DNA and germ line DNA from cell pellets. Starting in January 2016 at the University Hospital Ulm, 19 additional external sites started recruiting patients in March 2017. As of September 15th 2019, 2151 patients with newly diagnosed cancers could be recruited (2044 breast cancer; 107 ovarian cancer). Nearly all patients provided biological samples (tumor and liquid biopsy) and about 80% returned the standardized questionnaire. After 1 year follow-up, blood samples were available from more than 80% of the participating patients. The BRandO BIO study is a large prospective cohort study with integrated comprehensive biobank and evaluation of sociodemographic and life style factors of gynecological cancer patients in a well-defined geographical area in the South West of Germany. Continuous high patient recruitment and stable rates over 80% for returned questionnaires as well as for repeated blood sampling show high acceptance of the BRandO study program and confirms feasibility of the project.

Second fertility-sparing surgery and fertility-outcomes in patients with recurrent borderline ovarian tumors

Abstract Background At the time of recurrence, many borderline ovarian tumor (BOT) patients are still young with fertility needs. The purpose of this study is to evaluate the reproductive outcomes and recurrence rate of second fertility-sparing surgery (FSS) in women with recurrent BOTs. Methods Seventy-eight women of childbearing age diagnosed with recurrent BOTs from November 2009 to 2020 whose primary treatment was FSS were included. Results The FIGO stage I disease accounted for 46.2% and serous BOT accounted for 87.2% in the study group. Forty-seven patients underwent second FSS, and the remaining 31 underwent radical surgery (RS). Seventeen patients relapsed again after second surgery, but no malignant transformation and tumor-associated deaths were reported. Compared to FIGO stage I, the FIGO stage III tumors were more likely to relapse, but there was no statistical difference in pregnancy rate among patients with different stages. In the second FSS group, recurrence rate was higher in patients who underwent oophorocystectomy compared to patients with unilateral salpingo-oophorectomy (USO), but the pregnancy rate was similar. There was no significant difference in postoperative recurrence risk between USO and RS. The recurrence rate was not associated with operative route (laparoscopy or laparotomy), or lymphadenectomy, or postoperative chemotherapy. Among the 32 patients who tried to conceive, the pregnancy rate was 46.9% and live birth rate was 81.3%. Conclusion Unilateral salpingo-oophorectomy is a safe procedure for FIGO stage I recurrent BOT patients with fertility needs, and can achieve a high postoperative pregnancy rate and live birth rate.

Should all cervical cancer patients with positive lymph node receive definitive radiotherapy: a population-based comparative study

The optimal initial management strategy for cervical cancer with lymph node metastases (LNM) remains a topic of ongoing debate. This study aimed to explore the correlation between surgery followed by postoperative radiotherapy (PORT) and definitive radiotherapy (RT), as well as their impact on the prognosis of patients with LNM. Patients with positive lymph nodes (PLNs) in 2009 FIGO stage I-III cervical cancer were selected from SEER database. Kaplan-Meier and log-rank analysis were utilized to assess survival outcomes. Cox and Interaction analyses were employed to compare the survival benefits. 2936 patients were included in this study. Multivariate analysis revealed the choice of primary treatment significantly impacted both cancer-specific survival (CSS) and overall survival (OS), serving as an independent prognostic factor for patients with LNM. After adjusting for imbalanced variables, surgery plus PORT exhibited significant improvements in CSS and OS in the stage I-II and PLNs ≤ 5 subgroups. However, no statistically significant difference was observed between the two treatment modalities in stage III and PLNs > 5 subgroups. Through interaction analysis, it was observed that stage I-II and PLNs ≤ 5 subgroups exhibited a significant survival benefit from surgery plus PORT. Surgery plus PORT could lead to improved outcomes for cervical cancer in patients with stage I-II or PLNs ≤ 5. However, this approach did not apply to patients with stage III or PLNs > 5. Therefore, a comprehensive assessment of LNM and local tumor spread should guide rationalized treatment modalities when managing patients presenting LNM.

Oncologic outcomes of fertility-sparing surgery in early stage epithelial ovarian cancer: a population-based propensity score-matched analysis

To evaluate the safety of fertility-sparing surgery (FSS) in reproductive women (younger than 50 years) with early epithelial ovarian cancer (EOC). Reproductive women diagnosed with stage I EOC in the Surveillance, Epidemiology and End Results (SEER) database were identified. Surgeries that did not undergo hysterectomy and/or bilateral salpingo-oophorectomy were categorized as FSS, whereas non-FSS included bilateral salpingo-oophorectomy and hysterectomy. Propensity-score matching (PSM) was conducted to balance the covariates. Risk factor was identified by COX analysis. Kaplan-Meier curves were performed to evaluate the overall survival (OS) and cancer-specific survival (CSS). 3556 patients with stage I EOC were identified and divided into non-FSS group and FSS group. After PSM, 625 pairs of patients with stage I EOC were included. FSS was not inferior to non-FSS in the OS curve [HR 0.9127, 95% CI (0.6971 ~ 0.1.195), P = 0.5174; HR: 0.9378, 95% CI (0.6358 ~ 0.1.383), P = 0.7460] and the CSS curve [HR 0.8284, 95% CI (0.5932 ~ 1.157), P = 0.2949; HR 0.9003, 95% CI (0.5470 ~ 1.482), P = 0.6803] both in overall cohort and in matched cohort. Univariate COX analysis identified older age (45-49), moderate-differentiated to un-differentiation grade, IC stage, bigger tumor size (> 10 cm) and chemotherapy as risk factors of prognostic outcome (P < 0.1). Not only in univariate subgroup analyses but also in bivariate factors subgroup analysis, the evidence was not enough to regard FSS as a harmful factor compared with non-FSS. Fertility-sparing surgery was comparable to non-FSS in terms of survival in reproductive women with stage I EOC. Patients with high-risk factors could also consider FSS as an effective alternative compared with non-FSS.

Psychological distress in cervical cancer screening: results from a German online survey

Abstract Purpose The PODCAD study aimed at assessing the degree of psychological stress that women experience due to notification of an abnormal Papanicolaou (Pap) smear finding or a positive human papillomavirus (HPV) test result. Methods We designed a survey to address the question of psychological burden due to abnormal Pap smear results and/or positive HPV tests. In this online campaign approach, we aimed to reach &gt; 2000 women all over Germany irrespective of kind and number of abnormal screening findings. We asked for different kinds of anxiety, distress and uncertainty regarding both, Pap and HPV status. Results A total of 3753 women completed the survey at least partially, and almost 2300 fully completed the survey. Of these, more than 50% were affected already since more than 1 year, and almost half of them had experienced at least three Pap smears in follow-up examinations. Almost 70% of the women were afraid of developing cancer. Intriguingly, almost half of the women with abnormal findings were not aware of their stage of the Pap smear. Furthermore, almost 30% of the women displayed signs of a post-traumatic stress disorder. Conclusion Abnormal results in cervical cancer screening have an impact on patients’ psychology, irrespective of the knowledge and severity of the findings. Better information concerning risks and benefits of cervical cancer screening and about the meaning of the outcome of its procedures are required to decrease this anxiety.

Protective operative techniques in radical hysterectomy in early cervical carcinoma and their influence on disease-free and overall survival: a systematic review and meta-analysis of risk groups

Abstract Purpose Radical hysterectomy with pelvic lymphadenectomy presents the standard treatment for early cervical cancer. Recently, studies have shown a superior oncological outcome for open versus minimal invasive surgery, however, the reasons remain to be speculated. This meta-analysis evaluates the outcomes of robotic and laparoscopic hysterectomy compared to open hysterectomy. Risk groups including the use of uterine manipulators or colpotomy were created. Methods Ovid-Medline and Embase databases were systematically searched in June 2020. No limitation in date of publication or country was made. Subgroup analyses were performed regarding the surgical approach and the endpoints OS and DFS. Results 30 studies fulfilled the inclusion criteria. Five prospective, randomized-control trials were included. Patients were analyzed concerning the surgical approach [open surgery (AH), laparoscopic surgery (LH), robotic surgery (RH)]. Additionally, three subgroups were created from the LH group: the LH high-risk group (manipulator), intermediate-risk group (no manipulator, intracorporal colpotomy) and LH low-risk group (no manipulator, vaginal colpotomy). Regarding OS, the meta-analysis showed inferiority of LH in total over AH (0.97 [0.96; 0.98]). The OS was significantly higher in LH low risk (0.96 [0.94; 0.98) compared to LH intermediate risk (0.93 [0.91; 0.94]). OS rates were comparable in AH and LH Low-risk group. DFS was higher in the AH group compared to the LH group in general (0.92 [95%-CI 0.88; 0.95] vs. 0.87 [0.82; 0.91]), whereas the application of protective measures (no uterine manipulator in combination with vaginal colpotomy) was associated with increased DFS in laparoscopy (0.91 [0.91; 0.95]). Conclusion DFS and OS in laparoscopy appear to be depending on surgical technique. Protective operating techniques in laparoscopy result in improved minimal invasive survival.

High PD-1 expression level is associated with an unfavorable prognosis in patients with cervical adenocarcinoma

AbstractPurposeThe effectiveness of immunotherapy for cervical adenocarcinoma (CA) has not been demonstrated yet. Programmed cell death 1 (PD-1), programmed cell death-ligand 1 (PD-L1), and CD8 may be used as biomarkers of response to immune therapy in CA patients. In the present study, we aimed to investigate whether the expression levels of PD-1, PD-L1, and CD8 can predict the prognosis of patients with CA and their response to immune checkpoint inhibition therapy.MethodsIn the present study, the clinical stage for all 82 patients with cervical adenocarcinoma was classified according to the guidelines of the International Federation of Gynecology and Obstetrics (FIGO); there were 5, 48, 5, 14, 8, and 2 patients with stage IA, IB, IIA, IIB, IIIB, and IVB disease, respectively. The levels of PD-1, PD-L1, and CD8 were analyzed by the immunohistochemical analysis of the formalin-fixed paraffin-embedded tumor samples. The correlation between the expression levels and patient prognosis was analyzed using the Kaplan–Meier method and univariate and multivariate Cox proportional hazard regression models.ResultsWe observed a significant inverse correlation between the expression of PD-1 and CD8 (p = 0.001, chi-square test). We also found a significant inverse correlation between the expression of PD-L1 and CD8 (p = 0.027). The overall survival and progression-free survival rates were significantly worse in patients with positive PD-1 expression (p = 0.031;p = 0.087, respectively).ConclusionOur results suggest that a high PD-1 expression is associated with a poor prognosis in patients with CA. Further research is necessary to identify the molecular mechanisms that mediate this association.

Potential suppressive functions of microRNA-504 in cervical cancer cells malignant process were achieved by targeting PAICS and regulating EMT

The present study aimed to investigate the effects of miR-504 in cervical cancer. Normal and cervical cancer tissue specimens derived from TCGA and GTEx databases were employed to analyze the miR-504 and PAICS (one of potential target gene of miR-504) expression. Kaplan-Meier strategy was applied to analyze the prognostic powers of miR-504 and PAICS. The proliferation, clonogenic ability, invasion, and migration of cervical cancer cells (C-33A and HeLa) were detected using Cell Counting Kit 8, colony formation, and transwell assays. Pearson correlation analysis was used to assess the correlation between miR-504 and PAICS, which was confirmed using luciferase reporter assay. The mRNA and protein levels were detected by qRT-PCR and western blot, respectively. TCGA data revealed that miR-504 expression might be decreased in cervical cancer, which was correlated with unfavorable prognosis. Further experiments exhibited that abnormal miR-504 expression negatively affected malignant cellular behaviors in cervical cancer, including proliferation, colony formation, invasion, and migration. PAICS was identified as a putative target of miR-504, and negatively related with miR-504 expression. PAICS expression was increased in cervical cancer and its high-regulation-induced worse outcomes of patients with cervical cancer. Rescue experiments indicated that PAICS restricted the impacts of miR-504 in cervical cancer cells. Analysis of western blot suggested that overexpression of PAICS overturned the miR-504-induced EMT inactivation. Our observations elucidated that miR-504, acting as a suppressor for the progression of cervical cancer, inhibits cell proliferation, invasion and migration, and mediates EMT via negatively regulating PAICS.

A 10-gene prognostic methylation signature for stage I–III cervical cancer

Cervical cancer (CC) patients usually have poor prognosis. The present study aims to find a DNA methylation signature for predicting survival of CC patients. We selected CC patients at pathological stage I-III with corresponding information on radiotherapy and overall survival (OS) from TCGA. Differential expression and methylation analysis was done between patients with and without radiotherapy. We selected feature genes using recursive feature elimination algorithm to build a support vector machine classifier. DNA methylation biomarkers predictive of prognosis were identified using a LASSO Cox-Proportional Hazards model to construct a prognostic scoring model. The classifier and the prognostic model were tested on the training set and the validation set. Nomogram combining risk score and prognostic clinical factors were used. We obtained 497 differentially expressed genes (DEGs) and 865 differentially methylated genes (DMGs). Fifteen feature genes were selected from the 292 common genes between the DEGs and the DMGs to construct a classification model for radiotherapy. A DNA methylation signature including 10 genes was identified and used to establish a prognostic scoring model. The 10-gene methylation signature could effectively separate patients into two risk groups with markedly different OS time. Predictive capability of the methylation signature was successfully confirmed on the validation set. A nomogram comprised of risk score, radiotherapy, and recurrence was applied, with calibration plots displaying good concordance between predicted and actual OS. The DEGs were involved in 12 KEGG pathways most of which were correlated with metastasis and proliferation of various cancers, such as pathways in cancer, basal cell carcinoma, transcriptional misregulation in cancer and ECM-receptor interaction. We Identified a 10-gene methylation signature for risk stratification of CC patients at pathological stages I-III, and ten methylation biomarkers might be novel therapeutic targets for CC.

Characterization of patients with vulvar lichen sclerosus and association to vulvar carcinoma: a retrospective single center analysis

Abstract Purpose Lichen sclerosus (LS) is a benign, cutaneous, chronic inflammatory (autoimmunological) disease. The differentiated vulvar intraepithelial neoplasia (dVIN) accounts for a precursor lesion of vulvar squamous cell carcinoma and is often associated with lichen sclerosus. Although the association between lichen sclerosus and vulvar carcinoma has long been recognized, there is a lack of evidence in literature. Methods This retrospective study examined pseudonymized data of 499 women diagnosed with vulvar pathology between 2008 and 2020 at the Department of Gynaecology and Obstetrics of Hannover Medical School (MHH). Data were further stratified for the time of onset, location of disease, accompanying disease, HPV status and progression of disease into vulvar squamous cell carcinoma (VSCC). Results In total, 56 patients were diagnosed with vulvar lichen sclerosus. The mean onset of disease was at 60.3 years of age. After subdividing cases of diagnosed LS into those who did not develop vulvar carcinoma in their course and those who did, the ages at onset are 52.66 ± 17.35 and 68.41 ± 10.87, respectively. The incidence of vulvar cancer in women diagnosed with lichen sclerosus was 48.2%. Twenty-five patients reported a diagnosis of VIN in their self-reported history. Conclusions In our retrospective study, we showed a trend between vulvar lichen sclerosus and VSCC. The difference between the two age groups of patients diagnosed with lichen sclerosus who developed vulvar carcinoma and those who did not is statistically significant. Our results highlight the importance to diagnose lichen sclerosus early to ensure adequate follow-up and prevent progression to VSCC.

Pelvic lymphadenectomy in vulvar cancer and its impact on prognosis and outcome

Abstract Background The value of pelvic lymphadenectomy (LAE) has been subject of discussions since the 1980s. This is mainly due to the fact that the relation between lymph node involvement of the groin and pelvis is poorly understood and therewith the need for pelvic treatment in general. Patients and Methods N = 514 patients with primary vulvar squamous cell cancer (VSCC) FIGO stage ≥ IB were treated at the University Medical Center Hamburg-Eppendorf between 1996 and 2018. In this analysis, patients with pelvic LAE (n = 21) were analyzed with regard to prognosis and the relation of groin and pelvic lymph node involvement. Results The majority had T1b/T2 tumors (n = 15, 78.9%) with a median diameter of 40 mm (11–110 mm). 17/21 patients showed positive inguinal nodes. Pelvic nodal involvement without groin metastases was not observed. 6/17 node-positive patients with positive groin nodes also had pelvic nodal metastases (35.3%; median number of affected pelvic nodes 2.5 (1–8)). These 6 patients were highly node positive with median 4.5 (2–9) affected groin nodes. With regard to the metastatic spread between groins and pelvis, no contralateral spread was observed. Five recurrences were observed after a median follow-up of 33.5 months. No pelvic recurrences were observed in the pelvic nodal positive group. Patients with pelvic metastasis at first diagnosis had a median progression-free survival of only 9.9 months and overall-survival of 31.1 months. Conclusion A relevant risk for pelvic nodal involvement only seems to be present in highly node-positive disease, therefore pelvic staging (and radiotherapy) is probably unnecessary in the majority of patients with node-positive VSCC.

Anxiety in women referred for colposcopy: a prospective observational study

Abstract Purpose To evaluate the occurrence of anxiety in women attending a colposcopic examination within the new cervical cancer screening in Germany. Methods One hundred and fifty-six patients were asked to fill out Spielbergers STAI inventory form prior to their colposcopic examination. For the statistical analysis, a two by two between-group design was applied including the following group factors: the repeat factors included patients, who presented to our centre of dysplasia for the first time (new) and patients who have had an examination in our centre before (repeat). Further, the factor diagnosis included two groups: first, patients with cervical dysplasia and second, patients with vulva diseases. Results The analysis of the STAI results showed that patients presenting with cervical dysplasia for the first time had the highest levels of anxiety, directly followed by new patients in the vulva group. The ANOVA revealed a main effect of the repeat factor, F(1,140) = 7.53, p = 0.007. There was no significant effect of diagnosis. Conclusion Regardless of the diagnosis, patients being transferred for a colposcopy within the cervical cancer screening program for the first time have very high anxiety levels. The prospect of a potentially painful examination seems to be a key factor. Only a scientific evaluation of the new cervical cancer screening will be able to show if the rising numbers of colposcopic examinations is really worth the risk of exposing so many more women to the emotional distress of a colposcopy.

A risk factor analysis of complications after surgery for vulvar cancer

Abstract Introduction Despite the less frequent use of surgery in patients with vulvar cancer, the high rates of postoperative complications are still a matter of concern. The aim of the present study was to identify risk factors that influence postoperative complications rates in vulvar cancer and identify specific clinical parameters that may influence their incidence. Materials Patients who underwent curative-intent surgery for squamous cell carcinoma of the vulva from 2003 to 2018 were selected. All patient characteristics were analyzed as risk factors for the development of postoperative lymphocele, lymphedema, and wound dehiscence. The patients were followed up for 2 years postoperatively. Results The investigation comprised 121 patients, of whom 18.1% developed wound dehiscence, 17.7% a lymphocele, and 20.4% lymphedema. We found no significant evidence of an association between patient’s characteristics and postoperative complications. The depth of tumor invasion and the appearance of lymph-node metastasis were significantly associated with postoperative complications. Free resection margins of 5 mm or more were associated with a reduced risk of postoperative complications compared to resection margins less than 5 mm. No complications were encountered after sentinel node biopsy (SNB). Complication rates were associated with inguinofemoral lymphadenectomy, but not with the extent of lymphadenectomy. The development of a lymphocele or wound dehiscence may be correlated with the development of long-term lymphedema. Conclusion FIGO stage at diagnosis influences the risk of postoperative complications. The use of SNB minimized postoperative complications. Correlations between the free microscopic resection margin distance and the risk of postoperative wound dehiscence must be investigated further.

Performance of three colposcopic images for the identification of squamous and glandular cervical precursor neoplasias

Abstract Purpose To evaluate prevalence and diagnostic performance of three colposcopic images to diagnose squamous and glandular cervical precursor neoplasias. Methods Cross-sectional study, conducted through analysis of stored digital colposcopic images. To evaluate the diagnostic performance of three images, herein named grouped glands, aceto-white villi, and atypical vessels, for detection of adenocarcinoma in situ (AIS) and cervical squamous intraepithelial neoplasias (CIN) grades 2 and 3, calculations of sensitivity, specificity, accuracy, positive likelihood ratio, receiver operating characteristic (ROC) curve, and area under the curve (AUC) were made, with their respective 95% confidence intervals. Results Grouped glands, aceto-white villi, and atypical vessels images had: prevalence of 21.3, 53.8, and 33.8% in patients with AIS, and 16.2, 19.5, and 9.3% in those with CIN 2 and 3; for the diagnosis of AIS, sensitivity of 21.3, 53.8, and 33.8%, specificity of 89.8, 95.2, and 94.9%, accuracy of 76.6, 87.2, and 83.1%, positive likelihood ratio of 2.1, 11.2, and 6.6, and AUC of 0.55, 0.74, and 0.64; for the diagnosis of CIN 2 and 3, sensitivity of 16.2, 19.5, and 9.3%, specificity of 89.8, 95.2, and 94.9%, accuracy of 39.4, 43.4, and 36.3%, positive likelihood ratio of 1.6, 4.1, and 1, 8, and AUC of 0.53, 0.57, and 0.52, respectively. Conclusion Prevalence and accuracy of the three images were higher for the diagnosis of glandular than squamous cervical precursor neoplasias. Sensitivity, specificity, positive likelihood, and AUC of aceto-white villi and atypical vessels images were higher for the diagnosis of glandular than squamous cervical precursor neoplasias.

Sentinel lymph node biopsy in vulvar cancer: status, level of knowledge, and counseling in outpatient setting

Abstract Purpose Evaluating the counseling of patients with vulvar cancer in outpatient setting regarding the application of sentinel lymph node dissection (SLND), the selection of hospitals for further treatment, and level of knowledge. Methods A questionnaire containing 29 questions about SLND in vulvar cancer was sent to gynecologists in Lower Saxony. The questionnaire contained multiple choice questions and open questions. The study was approved by the local ethics committee. Results The median age of the 86 respondents was 54 (26–66) years. Most participants (83.1%) reported to only treat one to five patients with vulvar cancer per year. Interestingly, 70.5% of the gynecologists send their patients to university hospitals and 64.1% to hospitals offering maximum care, respectively. Of all, 32.7% replied that SLND was performed rarely or never in their patients. The gynecologists answered that only 36.7% of the patients are well informed about advantages and possible disadvantages of SLND. Most (84%) felt responsible to counsel patients on treatment decisions independently from or additionally to the hospital. Of all, 72% replied that they are not completely sure about the exact recurrence rates after SLND. Of notice, 66% believe that SLND for vulvar cancer is safe if applied in specialized centers and 92% stated that focusing treatment on specialized centers is required for best results. Conclusion SLND for vulvar cancer is widely accepted and regularly recommended among gynecologists. Outpatient doctors report to send most patients to specialized centers. However, it appears that patients remain uninformed after counseling in the clinics and that there is a lack of detailed knowledge about risks and complication rates of groin treatment in the outpatient setting.

Sensitivity of frozen section analysis in patients with ovarian adult granulosa cell tumor, a multi-center study

We aimed to demonstrate the sensitivity of frozen section for patients with adult granulosa cell tumor (AGCT) and analyze the clinico-pathological factors that may be associated with sensitivity. This is a multicenter study including data of 10 Gynecological Oncology Departments. Frozen-section results of patients who had ovarian AGCT at the final pathology report were retrospectively analyzed. The relation between clinico-pathological characteristics such as age, tumor size, Ca-125 level, presence of ascites, omental metastasis, menopausal status and peritoneal cytology, and the sensitivity of frozen section in patients with AGCT were evaluated. The sensitivity of frozen section diagnosis was determined by comparing the frozen section result with the final pathological diagnosis. Frozen section results of 274 patients with AGCT were obtained. The median age of the patients was 52 years (range, 17-82 years). Totally, 144 (52.7%, n = 273) patients were postmenopausal. The median tumour size was 90 mm (range, 9-700 mm). The median preoperative Ca-125 level was 23 IU/mL (range, 2-995 IU/mL). The sensitivity of frozen section for detecting AGCT was 76.3%. Any association between the sensitivity of frozen section and menopausal status, presence of ascites, positive cytology, omental metastasis, tumor size, Ca-125 level, age could not be shown. It is important to know the diagnosis of AGCT intraoperatively, and we demonstrated the sensitivity of frozen-section for these tumors as 76.3%.

Perioperative morbidity of different operative approaches in early cervical carcinoma: a systematic review and meta-analysis comparing minimally invasive versus open radical hysterectomy

Abstract Purpose Radical hysterectomy and pelvic lymphadenectomy is the standard treatment for early cervical cancer. Studies have shown superior oncological outcome for open versus minimal invasive surgery, but peri- and postoperative complication rates were shown vice versa. This meta-analysis evaluates the peri- and postoperative morbidities and complications of robotic and laparoscopic radical hysterectomy compared to open surgery. Methods Embase and Ovid-Medline databases were systematically searched in June 2020 for studies comparing robotic, laparoscopic and open radical hysterectomy. There was no limitation in publication year. Inclusion criteria were set analogue to the LACC trial. Subgroup analyses were performed regarding the operative technique, the study design and the date of publication for the endpoints intra- and postoperative morbidity, estimated blood loss, hospital stay and operation time. Results 27 studies fulfilled the inclusion criteria. Five prospective, randomized-control trials were included. Meta-analysis showed no significant difference between robotic radical hysterectomy (RH) and laparoscopic hysterectomy (LH) concerning intra- and perioperative complications. Operation time was longer in both RH (mean difference 44.79 min [95% CI 38.16; 51.42]), and LH (mean difference 20.96 min; [95% CI − 1.30; 43.22]) than in open hysterectomy (AH) but did not lead to a rise of intra- and postoperative complications. Intraoperative morbidity was lower in LH than in AH (RR 0.90 [0.80; 1.02]) as well as in RH compared to AH (0.54 [0.33; 0.88]). Intraoperative morbidity showed no difference between LH and RH (RR 1.29 [0.23; 7.29]). Postoperative morbidity was not different in any approach. Estimated blood loss was lower in both LH (mean difference − 114.34 [− 122.97; − 105.71]) and RH (mean difference − 287.14 [− 392.99; − 181.28]) compared to AH, respectively. Duration of hospital stay was shorter for LH (mean difference − 3.06 [− 3.28; − 2.83]) and RH (mean difference − 3.77 [− 5.10; − 2.44]) compared to AH. Conclusion Minimally invasive radical hysterectomy appears to be associated with reduced intraoperative morbidity and blood loss and improved reconvalescence after surgery. Besides oncological and surgical factors these results should be considered when counseling patients for radical hysterectomy and underscore the need for new randomized trials.

Assessment of cervical vascularization density in patients with locally advanced squamous cell cervical carcinoma evaluated in colour Doppler and power Doppler functions

Abstract Purpose The aim of the prospective study was to assess changes during treatment and prognostic significance of cervical vascularization density in patients with cervical squamous cell carcinoma (SCC) staged II B and III B and to find relationship of cervical vascularization density with tumour diameter, grading, staging and age of patients. Methods The study group included 50 patients who underwent transvaginal Doppler ultrasonography prior to chemoradiotherapy, after external beam radiation therapy (EBRT) and 6 weeks after HDR brachytherapy. The colour Doppler (CD) vascularity index (CDVI) and the power Doppler (PD) vascularity index (PDVI) in cervical tumour were examined. Results CDVI and PDVI values decreased significantly during radiotherapy (0.13 (95% CI 0.09–0.16); 0.09 (95% CI 0.07–0.11) and 0.05 (95% CI 0.03–0.06) for CDVI (p &lt; 0.001) and 0.26 (95% CI 0.22–0.31); 0.18 (95% CI 0.14–0.22) and 0.08 (95% CI 0.06–0.11) for PDVI (p &lt; 0.001)). No statistically significant associations of CDVI and PDVI with tumour diameter, grading, staging and age of patients were found. The higher (above median) CDVI values before EBRT were associated with better OS (p = 0.041). The higher (above median) PDVI values before EBRT were associated with superior DFS (p = 0.011) and OS (p &lt; 0.001). DFS and OS did not differ significantly regarding CDVI and PDVI values after EBRT and after the treatment. Conclusions In the study group, cervical vascularization density evaluated in CD and PD functions did not depend on tumour diameter, grading, staging and age of patients and decreased during radiotherapy. The prognosis for our patients with CDVI and PDVI before the treatment above the median value was better than compared to patients with these parameters below the median value.

Evaluating tumor chemosensitivity: a head-to-head comparison of the prognostic value of KELIM (modeled CA125 elimination rate constant K) and RECIST 1.1 (radiological response valuation criteria in solid tumors) in ovarian cancer

Abstract Purpose The aim of the study was to analyze KELIM (modeled CA125 ELIMination rate constant K) and RECIST 1.1. (radiological response valuation criteria in solid tumors) as indicators of tumor chemosensitivity and their role in predicting patient prognosis. Methods This retrospective single-center analysis included 165 consecutive patients with advanced newly diagnosed high-grade serous ovarian, fallopian tube, or primary peritoneal cancer who underwent surgical and chemotherapeutical treatment at the Department of Gynecologic Oncology. Results There were significant differences in OS between the neoadjuvant and adjuvant groups of patients (20.87 vs 32.88 months). There was a significant difference in the response to treatment assessed in imaging studies between the groups, with higher rates of complete and partial responses to treatment among PDS patients ( p  = 0.002). However, upon a separate analysis of the NACT and PDS subgroups, the multivariate analysis showed no significant influence of KELIM and RECIST 1.1. response on patients’ overall survival of patients. Conclusion Our findings showed no significant associations between KELIM, RECIST and overall survival of patients. However, further studies on bigger homogenous population samples are required to confirm our findings.

Association of preoperative cone biopsy with recurrences after radical hysterectomy

Abstract Objective To evaluate association of preoperative cone biopsy with the probability of recurrent disease after radical hysterectomy for cervical cancer. Methods This is a retrospective single-center study. Patients with cervical cancer stage IA1 with LVSI to IIA2 and squamous, adenosquamous and adenocarcinoma subtype were included. Patients were analyzed for general characteristics and recurrence-free survival (RFS). Results In total, of 480 patients with cervical cancer, 183 patients met the inclusion criteria (117 with laparoscopic and 66 with open surgery). The median tumor diameter was 25.0 mm (range 4.6–70.0 mm) with 66 (36.2%) patients having tumors smaller than 2 cm. During median follow-up of 54.0 months (range 0–166.0 months), the RFS for the laparoscopic cohort was 93.2% and 87.5% at 3 and 4.5 years, and 79.3% for the open cohort after 3 and 4.5 years, respectively. In total, 17 (9.3%) patients developed recurrent disease, 9 (7.3%) after laparoscopic, and 8 (12.1%) after open surgery. No preoperative cone biopsy (OR 9.60, 95% CI 2.14–43.09) as well as tumor diameter &gt; 2 cm (OR 5.39, 95% CI 1.20–24.25) were significantly associated with increased risk for recurrence. In multivariate analysis, only missing preoperative cone biopsy was significantly associated with increased risk for recurrence (OR 5.90, 95% CI 1.11–31.29) Conclusion There appears to be a subgroup of patients (preoperative cone biopsy, tumor diameter &lt; 2 cm) with excellent survival and low risk for recurrence after radical hysterectomy which might benefit from the advantages of laparoscopic surgery.

CD34 and Bcl-2 as predictors for the efficacy of neoadjuvant chemotherapy in cervical cancer

Abstract Background Successful neoadjuvant chemotherapy (NACT) could improve the surgical resection rate and radical curability of patients with cervical cancer, but only a subset of patients benefits. Therefore, identifying predictive biomarkers are urgently needed. The aim of this study was to evaluate the predictive value of CD34 and Bcl-2 in the NACT effectiveness of cervical cancer. Methods Sixty-seven patients with locally advanced cervical cancer (FIGO stages IB3, IIA2 or IIB) were classified into two groups based on effective (n = 48) and ineffective (n = 19) response to NACT. Immunohistochemistry was employed to identify CD34 and Bcl-2 expression before and after NACT. We analyzed the associations between the pre-NACT expression of these two biomarkers and the response of NACT. The expression of these two biomarkers before and after NACT was also assessed and compared. Results More patients were CD34 positive expression before NACT in effective group compared to ineffective group (p = 0.005). However, no statistically significant difference in Bcl-2 expression before NACT were found between two groups (p = 0.084). In NACT effective group, the expression of both CD34 and Bcl-2 after NACT are down-regulated (p &lt; 0.001 and p &lt; 0.001, respectively), while there are no statistical differences between the pre- and post-NACT expression of CD34 and Bcl-2 in NACT ineffective group (p = 0.453 and p = 0.317, respectively). Conclusion The positive CD34 expression before NACT may serve as a predictive biomarker for NACT of cervical cancer, but the pre-NACT expression of Bcl-2 is not an independent predictor. The down-regulated expression of these two indicators after NACT may indicate effective NACT.

Association of preoperative conization with recurrences after laparoscopic radical hysterectomy for FIGO 2018 stage IB1 cervical cancer

Abstract Objective To evaluate association of preoperative conization with recurrences after laparoscopic radical hysterectomy (LRH) for FIGO 2018 stage IB1 cervical cancer. Methods This is a retrospective single-center study. Patients who underwent LRH for cervical cancer with squamous, adenosquamous and adenocarcinoma subtype from January 2014 to December 2018 were reviewed. All patients were restaged according to the 2018 FIGO staging system. Those who were in FIGO 2018 stage IB1 met the inclusion criteria. General characteristics and oncologic outcomes including recurrence-free survival (RFS) were analyzed. Results A total of 1273 patients were included in the analysis. 616 (48.4%) patients underwent preoperative biopsy, and 657 (51.6%) patients underwent conization. Residual disease was observed in 822 (64.6%) patients. During a median follow-up of 50.30 months, 30 (2.4%) patients experienced recurrence. The univariate analysis showed that patients who had larger tumor diameter, the presence of residual tumor at final pathology, and underwent adjuvant treatment had a significant higher risk of recurrence (P &lt; 0.01). Conversely, patients who underwent conization were significantly less likely to experience recurrence (P = 0.001). In the multivariate analysis, the independent risk factor associated with an increased risk of recurrence was resident macroscopic tumor (HR: 38.4, 95% CI 4.20–351.64, P = 0.001). On the contrary, preoperative conization was associated with a significantly lower risk of recurrence (HR: 0.26; 95% CI 0.10–0.63, P = 0.003). The Kaplan–Meier curves showed patients who underwent conization had improved survival over those who underwent biopsy (5 year RFS: 98.6 vs 95.1%, P = 0.001). The 5 year RFS of patients with residual tumor was significantly different (R0: 99.2%, R1: 97.4%, R2: 93.6%, P &lt; 0.001), especially the patients with residual macroscopic tumor after conization (R0: 99.5%, R1: 99.0%, R2:92.4%, P = 0.006). Conclusion Preoperative conization and the absence of residual tumor at the time of surgery might play a protective role in patients with FIGO 2018 IB1 cervical cancer following LRH, which support the theory of the influence of intraoperative tumor spread during radical hysterectomy. Further prospective evidence is needed.

Pregnancy outcome and risk of recurrence after tissue-preserving loop electrosurgical excision procedure (LEEP)

Abstract Background/purpose This study aims to investigate whether women with cervical dysplasia after LEEP have an increased risk of pregnancy/childbirth complications or recurrence of dysplasia in an upcoming pregnancy. Methods Data from 240 women after LEEP were analysed retrospectively. The reference group consisted of 956 singleton births. Fisher’s and Wilcoxon rank tests were used to detect differences between groups. Using logistic regressions, we analysed the effect of surgery-specific aspects of LEEP on pregnancy/childbirth complications and the frequency of CIN recurrences. Results We found that tissue-preserving LEEP did not lead to premature birth or miscarriage and did not increase the likelihood of CIN recurrence. We did not observe differences regarding preterm birth [&lt; 37 (p &lt; 0.28) &lt; 34 (p &lt; 0.31), &lt; 32 weeks of gestation (p &lt; 0.11)] or birth weight (&lt; 2500 g (p &lt; 0.54), &lt; 2000 g (p &lt; 0.77) between groups. However, women after LEEP exhibit a higher risk of premature rupture of membranes (PROM) at term (p &lt; 0.009) and vaginal infections (p &lt; 0.06). Neither volume nor depth of the removed tissue nor an additional endocervical resection seems to influence the likelihood of premature birth or early miscarriage. Performing an endocervical resection protects against CIN recurrence (OR 0.0881, p &lt; 0.003). Conclusions After tissue-preserving LEEP, there is an increased risk of vaginal infections and PROM at term in consecutive pregnancy. LEEP does not affect prematurity or miscarriage. The removal of additional endocervical tissue appears to be a protective factor against recurrence of CIN.

Proposal for a descriptive and differentiated presentation of the longitudinal impact of the new organized cancer screening guideline and HPV vaccination in Germany

Abstract Introduction Since 01/01/2020, the cervical cancer screening in Germany has been carried out due to the organized early cancer diagnosis guideline (oKFE-RL). In 2007, HPV vaccination was initiated in Germany. The main goal of both initiatives is to further reduce the incidence of invasive cervical cancer. To assess the effect of the new screening strategy in a timely manner, monitoring of short-term changes need to be considered. Ideally, the effects of both prevention methods would be presented together in one model. Materials and methods Because no change in the incidence of invasive cervical cancer is initially expected, the incidence of CIN 3 is used as a surrogate parameter to assess the effects of the prevention efforts. Based on expected additional effects of vaccination and co-testing, a model-based estimation of the expected CIN 3 incidence during the evaluation of the screening program is performed using the CIN 3 incidence in the Saarland population. Modeling results The oKFE-RL provides for two groups: Primary cytodiagnosis continues until 35 years of age. Here, in the next few years, CIN 3 incidence will be reduced not by the oKFE-RL but by the increasing proportion of vaccinated women. In the group over 35 years, co-testing was introduced with a stringent algorithm. Due to the higher sensitivity of the HPV test, significantly more CIN 3 are detected in the first round of 3 years and thus, the CIN 3 incidence initially increases. As these CIN 3 are absent in the second round, significantly fewer CIN 3 cases will be detected then. These effects suggest a global decrease in CIN 3 incidence of 25.8% after 6 years. Conclusion Observation of the age distribution curve of CIN 3 allows both effects of prevention to be assessed in a timely manner and separately. In the future, data from epidemiologic cancer registries should be incorporated into the model to replace modeling with real data.

Impact of endometrial carcinoma histotype on the prognostic value of the TCGA molecular subgroups

The Cancer Genome Atlas (TCGA) identified four prognostic subgroups of endometrial carcinoma: copy-number-low/p53-wild-type (p53wt), POLE-mutated/ultramutated (POLEmt), microsatellite-instability/hypermutated (MSI), and copy-number-high/p53-mutated (p53mt). However, it is still unclear if they may be integrated with the current histopathological prognostic factors, such as histotype. To assess the impact of histotype on the prognostic value of the TCGA molecular subgroups of endometrial carcinoma. A systematic review and meta-analysis was performed by searching 7 electronic databases from their inception to April 2019 for studies assessing prognosis in all TCGA subgroups of endometrial carcinoma. Pooled hazard ratio (HR) for overall survival (OS) was calculated in two different groups ("all-histotypes" and "endometrioid"), using p53wt subgroup as reference standard; HR for non-endometrioid histotypes was calculated indirectly. Disease-specific survival and progression-free survival were assessed as additional analyses. Six studies with 2818 patients were included. In the p53mt subgroup, pooled HRs for OS were 4.322 (all-histotypes), 2.505 (endometrioid), and 4.937 (non-endometrioid). In the MSI subgroup, pooled HRs were 1.965 (all-histotypes), 1.287 (endometrioid), and 6.361 (non-endometrioid). In the POLEmt subgroup, pooled HRs were 0.763 (all-histotypes), 0.481 (endometrioid), and 2.634 (non-endometrioid). Results of additional analyses were consistent for all subgroups except for non-endometrioid POLEmt carcinomas. Histotype of endometrial carcinoma shows a crucial prognostic value independently of the TCGA molecular subgroup, with non-endometrioid carcinomas having a worse prognosis in each TCGA subgroup. Histotype should be integrated with molecular characterization for the risk stratification of patients in the future.

Intracavitary brachytherapy with additional Heyman capsules in the treatment of cervical cancer

Abstract Purpose Brachytherapy is a mandatory component of primary radiochemotherapy in cervical cancer. The dose can be applied with a traditional intracavitary approach (IC alone) or with multiple catheter brachytherapy to optimize dose distribution in an individual concept. We therefore evaluated whether the utilization of a tandem–ring applicator plus additional intracavitary applicators (add IC) provides an advantage over the traditional IC alone approach, as this method is less time consuming and less invasive compared to a combined intracavitary/interstitial brachytherapy. Methods Twenty three procedures of intracavitary brachytherapy for cervical cancer with additional intracavitary applicators performed in seven patients treated between 2016 and 2018 in our institution were included in this study. Plans were optimized for D90 HR-CTV with and without the utilization of the additional applicators and compared by statistical analysis. Results D90 for HR-CTV was 5.71 Gy (±1.17 Gy) for fractions optimized with add IC approach and 5.29 Gy (±1.24 Gy) for fractions without additional applicators (p &lt; 0.01). This translates to a calculated mean EQD2 HR-CTV D90 of 80.72 Gy (±8.34 Gy) compared to 77.84 Gy (±8.49 Gy) after external beam therapy and four fractions of brachytherapy for add IC and IC alone, respectively (p &lt; 0.01). The predictive value of improved coverage of HR-CTV in the first fraction was high. Conclusion In a subgroup of cases, the addition of intracavitary Heyman capsules can be an alternative to interstitial brachytherapy to improve the plan quality compared to standard IC alone brachytherapy. The benefit from the addition of applicators in the first fraction is predictive for the following fractions.

Effects of hysteroscopic surgery combined with progesterone therapy on fertility and prognosis in patients with early endometrial cancer and atypical endometrial hyperplasia or endometrial intraepithelial neoplasia: a meta-analysis

This meta-analysis aimed to evaluate the effects of hysteroscopic surgery combined with progesterone therapy on fertility and prognosis in patients with early endometrial cancer (EC), atypical endometrial hyperplasia (AEH), or endometrial intraepithelial neoplasia (EIN). Studies on hysteroscopic surgery combined with progesterone therapy for patients with early-stage EC, AEH, or EIN were searched from Embase, Web of Science, PubMed, and Cochrane Library databases. The included studies contained one or more of the following outcome variables: pregnancy rate, live birth rate, complete response (CR) rate, and recurrence rate after conservative treatment. The meta-analysis was performed using Stata. 13 pieces of literature containing 239 patients with EC and 199 patients with AEH/EIN were included. As per the results of meta-analysis, the pregnancy rates of EC patients and AEH/EIN patients were 49% (95% CI 33-65%) and 47% (95% CI 31-64%), respectively, and the live birth rates were 45% (95% CI 32-58%) and 44% (95% CI 34-54%), respectively. CR rates of EC patients and AEH/EIN patients were 90% (95% CI 85-94%) and 100% (95% CI 97-100%), respectively, and the disease recurrence rates were 17% (95% CI 8-28%) and 11% (95% CI 3-23%), respectively. Hysteroscopic surgery combined with progesterone was linked to an improved overall response rate, reduced disease recurrence rate, and increased pregnancy and live birth rates among patients with EC and AEH/EIN.

First experiences with PET-MRI/CT in radiotherapy planning for cervical cancer

Abstract Purpose PET-CT has recently been included in the NCCN staging recommendations for cervical cancer stages II–IV and is already routinely applied to radiotherapy planning for other malignancies, as it is expected to provide higher accuracy for the detection of areas with tumor cell spread. In this study, we report on our first experiences of PET-based radiotherapy planning for cervical cancer. Methods 19 patients with cervical cancer that underwent pre-therapeutic PET imaging treated at our institution between January 2016 and April 2019 were included in the study. Information on the primary tumor, lymph node involvement, metastatic spread and changes in the radiotherapy procedure based on the PET findings are described. Results A previously unknown primary tumor extension that was detected by PET imaging in one patient. In patients who underwent a PET before the systematic pelvic and paraaortic lymphonodectomy (n = 2), PET was false negative for pelvic lymph node metastases in 50%. In patients who underwent a PET after the systematic LNE (n = 13), additional lymph node metastases were detected in seven patients (53.80%). Distant metastases were suspected in three patients (15.7%) based on PET imaging. The suspicion was confirmed in one patient (peritoneal spread) and excluded in two patients (supra-diaphragmatic lymph nodes). In 13 patients (68.4%), RT procedures were altered due to findings in PET imaging. Conclusion PET-based radiochemotherapy planning may improve control rates by identifying areas of tumor cell spread eligible for dose escalation. False positivity, however, should be excluded in patients with findings that lead to major modifications of the therapeutic strategy.

A meta-analysis of survival after minimally invasive radical hysterectomy versus abdominal radical hysterectomy in cervical cancer: center-associated factors matter

Abstract Purpose To explore the possible factors that contributed to the poor performance of minimally invasive surgery (MIS) versus abdominal surgery regarding progression-free survival (PFS) and overall survival (OS) in cervical cancer. Methods MEDLINE, EMBASE, Cochrane Library and Web of Science were searched (January 2000 to April 2021). Study selection was performed by two researchers to include studies reported oncological safety. Summary hazard ratios (HRs) and 95% confidence intervals (CIs) were combined using random-effect model. Subgroup analyses were stratified by characteristics of disease, publication, study design and treatment center. Results Sixty-one studies with 63,369 patients (MIS 26956 and ARH 36,049) were included. The overall-analysis revealed a higher risk of recurrence (HR 1.209; 95% CI 1.102–1.327) and death (HR 1.124; 95% CI 1.013–1.248) after MIS versus ARH expect in FIGO IB1 (FIGO 2009 staging) patients with tumor size less than 2 cm. However, subgroup analyses showed comparable PFS/DFS and OS in studies published before the Laparoscopic Approach to Cervical Cancer (LACC) trial, published in European journals, conducted in a single center, performed in centers in Europe and in centers with high sample volume or high MIS sample volume. Conclusion Our findings highlight possible factors that associated with inferior survival after MIS in cervical cancer including publication characteristics, center-geography and sample volume. Center associated factors were needed to be taken into consideration when evaluating complex surgical procedures like radical hysterectomy.

Risk factors and predictive modeling for occult endometrial cancer in women with atypical hyperplasia: a retrospective study

Abstract Purpose Atypical endometrial hyperplasia (AEH) is a known precursor to endometrioid endometrial carcinoma. However, occult carcinoma may already be present at diagnosis, complicating surgical planning. Accurate preoperative risk stratification is crucial, especially for guiding the selective use of sentinel lymph node biopsy. This study aimed to identify predictors of occult carcinoma and develop a model to estimate the risk of malignancy. Methods We conducted a retrospective case–control study of 101 women diagnosed with AEH who underwent hysterectomy between 2010 and 2024 at Galilee Medical Center. Clinical, metabolic, and imaging data were extracted. Patients were stratified based on the final pathology into two groups: those with occult carcinoma and those with AEH only. Multivariable logistic regression was employed to identify independent predictors and construct a predictive model. Results Occult endometrial carcinoma was identified in 37 women (36.6%). Women with occult endometrial carcinoma were older and more likely to present with postmenopausal bleeding. Occult carcinoma was more frequently detected after Pipelle biopsy than after hysteroscopy or dilation and curettage (43.2% vs. 17.2%). In multivariable analysis, Pipelle biopsy (OR 4.68), hyperlipidemia (OR 5.86), obesity (OR 2.97), and increasing age (OR 1.07 per year) were independently associated with occult carcinoma. A predictive model estimated individual risk ranging from 5.6% to 95.0% according to accumulation of risk factors. Conclusion Older age, biopsy method, obesity, hyperlipidemia, and bleeding presentation are independently associated with an occult endometrial carcinoma in women with atypical endometrial hyperplasia. The proposed model may support preoperative risk stratification and counseling, but it requires external validation before clinical use, including decisions regarding sentinel lymph node biopsy.

Analysis of immunohistochemical characteristics and recurrence after complete remission with fertility preservation treatment in patients with endometrial carcinoma and endometrial atypical hyperplasia

To investigate the relationship between immunohistochemical characteristics and recurrence after complete remission (CR) with fertility preservation treatment in patients with endometrial cancer (EC) and endometrial atypical hyperplasia (AH). The clinical data and immunohistochemical results of 53 patients with EC and 68 patients with AH admitted to Peking University People's Hospital from January 2010 to January 2021 were retrospectively analyzed. Patients were divided into two groups according to whether recurrence after complete remission (CR): group 1: recurrence after CR; group 2: no recurrence after CR, for statistical analysis. (1) The expression rate of ER in group 1 was lower than that in group 2, (P  0.05); (2) combination index ER/ Ki-67 row ROC curve analysis, there was a significant difference (P < 0.01), the best cut-off value was 3.55, sensitivity 0.730, specificity 1.000, Youden index 0.730. The 3-year RFS of high rate patients was 100%, and that of low rate patients was 42.3%, P < 0.01. The expression rate of Ki-67 is of great significance in predicting the recurrence of EC after fertility preservation therapy. The best cut-off value of combination index ER/ Ki-67 (3.55) was better than a single immunohistochemical marker in predicting recurrence of EC after fertility preservation treatment.

Synchronous/metachronous endometrial and colorectal malignancies in Taiwanese women: a population-based nationwide study

Endometrial cancer (EC) and colorectal cancer (CRC) may share a common genetic background. In a subset of patients, the two malignancies can coexist either at the time of diagnosis (synchronous) or develop consequently (metachronous). The purpose of this nationwide, population-based study was to investigate the occurrence and clinical outcomes of synchronous/metachronous EC/CRC in Taiwanese women. Data for women diagnosed with EC and/or CRC between 2007 and 2015 were retrospectively retrieved from the nationwide Taiwan Cancer Registry. Mortality data were obtained from the National Death Registry. Women with synchronous/metachronous EC/CRC versus EC or CRC were compared in terms of clinical characteristics and outcomes. Of the 62,764 Taiwanese women diagnosed with EC and/or CRC during the study period, 167 (0.3%) had synchronous/metachronous EC/CRC. Among them, 72 cases (43.1%) presented with EC followed by CRC, 66 (39.5%) with CRC followed by EC, and 29 (17.4%) with synchronous EC/CRC. Kaplan-Meier estimates for time-to-event data revealed that the 2-year risk rates of developing a metachronous tumor of interest (CRC or EC) in women diagnosed with an initial EC and CRC were 39.6% and 42.1%, respectively. The 5-year overall survival rates of women with metachronous EC/CRC who had an initial diagnosis of EC, CRC, and synchronous EC/CRC were 73.9%, 70.9%, and 37.0%, respectively. Endometrial cancer is the most common first tumor in Taiwanese women with metachronous EC/CRC. The 2-year risk rates of developing a metachronous tumor of interest (CRC or EC) in women diagnosed with an initial EC and CRC are not negligible. Surveillance for CRC is recommended for all women diagnosed with EC. The clinical outcomes of synchronous EC/CRC are markedly less favorable.

Effectiveness of robotic surgery for endometrial cancer: a systematic review and meta-analysis

Our current study was performed aimed at determining the efficacy and safety profile of robotic surgery (RS) compared to laparoscopic surgery (LPS) and laparotomy (LT) in the treatment of endometrial cancer on the basis of relevant studies. A systematic literature search was conducted based on appropriate keywords, using the Embase, Cochrane library, as well as PubMed. Our studiers also reviewed the key pertinent sources among the publications and included associated literatures published by June 2021. Odds ratios (ORs), mean difference (MD), as well as 95% confidence interval (95% CI) for each study were measured for further assessment and synthesis of outcomes. Thirty studies involving a total of 12,025 patients were eventually included in the current meta-analysis. Compared with LPS, RS could significantly decrease the estimated blood loss, the incidence of intraoperative complications, the length of hospital stay, and the rate of conversion, and increased the rate of readmission. Compared with LT, RS significantly decreased the estimated blood loss, blood transfusion volume, the length of hospital stay, the rate of total, intraoperative and postoperative complications, and the rate of readmission and re-operation, and increased the operative time. Considering the effects and safety profile of RS in terms of treating endometrial cancer, our study suggest that RS exerts superior outcomes than that of LPS and LT.

Publisher

Springer Science and Business Media LLC

ISSN

1432-0711