World Journal of Surgical Oncology

Knowledge, attitudes, and practices regarding chemotherapy-induced bone marrow suppression in ovarian cancer patients

This study aimed to investigate the knowledge, attitudes, and practices (KAP) of ovarian cancer patients regarding chemotherapy-induced bone marrow suppression. This cross-sectional study was conducted on ovarian cancer patients at the Hospital between March and October 2024, using a self-designed questionnaire. A total of 505 valid questionnaires were collected, with a 100% valid response rate. The average age of participants was 58.41 ± 6.64 years. The mean KAP and health literacy scores were 20.69 ± 6.24 (possible range: 0-18), 34.69 ± 4.97 (possible range: 10-50), 34.30 ± 7.07 (possible range: 9-45), and 8.18 ± 1.81 (possible range: 3-15), respectively. Pearson's correlation analysis showed positive interrelationships between KAP (r = 0.191, 0.315, P < 0.001), and negative correlations between KAP and health literacy (r=-0.326, -0.100, P < 0.05). Multivariate logistic analysis revealed positive associations of knowledge, attitude, education and cancer stage with practice (OR = 1.079, 4.369, P < 0.05), and negative associations between age and practice (OR = 0.905, 95%CI: 0.869-0.942, P < 0.001). In the adjusted SEM, education was directly associated with knowledge (Estimate = 3.63, P < 0.001). Direct associations were observed among KAP (Estimate = 0.238-0.311, P < 0.001), and between health literacy and knowledge (Estimate=-0.063, P < 0.001) or practice (Estimate=-1.050, P < 0.001). Ovarian cancer patients had sufficient knowledge, moderate attitude, positive practice and poor health literacy towards chemotherapy-induced bone marrow suppression. Educational and behavioral interventions are needed to promote better management of chemotherapy-induced bone marrow suppression.

An unusual case of post-menopausal bleeding

Metastasis from Renal cell carcinoma at presentation is seen in nearly one fifth of the patients and commonly occur to lung, bone and liver. Synchronous vaginal and cervical metastasis is extremely rare. Several pathways have been proposed of which blood reflux from left renal vein to ovarian vein is most plausible. The prognosis is usually very poor as they are often associated with disseminated metastasis. A 55-year-old women presented with post-menopausal vaginal bleeding, on examination a smooth mass occupying the vagina and obscuring the view of cervix with normal mucosa was found. Biopsy and Immunohistochemistry showed it to be renal cell carcinoma. Further investigations lead to identification of left renal mass with pulmonary, vaginal and cervical metastasis. Patient was started on Pazopanib 800 mg PO per day, and was lost to follow-up. Vaginal metastasis presenting as post-menopausal bleeding is one of the rarest presentation of renal cell carcinoma with only 3 cases reported in literature before this. Metastatic tumors to the vagina are more common than primary tumors and are mostly from cervix, endometrium and ovary. A high index of suspicion and through examination and investigation is the key to correct diagnosis and management.

Small bowel obstruction and ovarian cancer: insights from a propensity-score matched study in patients with and without hyperthermic intraperitoneal chemotherapy after cytoreductive surgery

Small bowel obstruction (SBO) affects ~ 30% of ovarian cancer (OC) patients, leading to readmission, debilitating symptoms, and death within one year. Cytoreductive surgery plus hyperthermic intraperitoneal chemotherapy (CRS/HIPEC) effectively controls peritoneal disease. We investigated primary CRS/HIPEC's impact on SBO and obstruction-free survival (OFS) in OC patients. A retrospective single-center cohort study of stage III/IV OC patients treated with primary optimal CRS (2014-2022) was performed. Patients who underwent upfront CRS/HIPEC vs. CRS only were matched for histology, age (> 65 years), extent of disease, FIGO stage, and surgery year, using a propensity scored full matching algorithm. CRS/HIPEC effect on OFS was determined using a weighted cox-regression model. OFS was measured from surgery to SBO/death. Overall, 102 patients were included, 29 underwent CRS/HIPEC and 73 CRS only. CRS/HIPEC had higher median number of upper abdominal procedures (4 [IQR: 3-5] vs. 1 [IQR: 0-4], p < 0.01). Postoperative major morbidity was similar (p = 0.62). After a median follow-up of 88.8 months, SBO occurred in 24.1% (n = 7) CRS/HIPEC vs. 42.0% (n = 34) CRS only (p = 0.12). Most SBOs were partial (CRS/HIPEC: 71.4%, CRS: 55.9%) and managed conservatively (CRS/HIPEC: 71.4%, CRS: 67.6%). Median OFS was 42.9 vs. 20.0 months (HR: 0.50 [95% CI 0.27-0.93], p = 0.028). One-year survival after initial SBO was 85.7% vs. 44.7%, respectively (HR: 0.79 [95% CI 0.39-1.61], p = 0.512). SBO after upfront CRS/HIPEC for OC occurred less frequently, was delayed, and had lower 1-year mortality compared to CRS alone. CRS, which includes upper abdominal exploration/surgery, coupled with HIPEC could enhance long-term peritoneal disease control in OC patients.

A case report on SMARCA4 deficient cervical adenocarcinoma with high-grade squamous intraepithelial lesion

SMARCA4-deficient cervical adenocarcinoma is an exceedingly rare and aggressive subtype of cervical malignancy that presents with clinicopathological features mimicking other types of cervical cancer, leaving no established treatment protocols available. This report describes a case of a 50-year-old woman in perimenopause who presented with an increase in vaginal discharge, discomfort in the external genitalia, and bleeding after intercourse. The imaging examination revealed a cervical mass accompanied by enlarged lymph nodes in the pelvic cavity. A cervical biopsy confirmed adenocarcinoma, with an initial clinical stage classified as International Federation of Gynecology and Obstetrics (FIGO) 2018 stage IIA1. The patient underwent a radical hysterectomy and pelvic lymph node dissection (PLND), during which it was found that the tumor had involved pelvic lymph nodes. The revised staging was Stage IIIC1. According to the postoperative pathologic analysis, the woman was diagnosed as adenocarcinoma with a poorly differentiated grade and with myoepithelial differentiation features. Immunohistochemical analysis supported the diagnosis of the SMARCA4-deficient adenocarcinoma that was accompanied by high-grade squamous intraepithelial lesion (HSIL) in its surroundings, indicating the presence of two distinct types of lesions. Postoperative review after one month revealed multiple lymph node metastases in the left neck. Pathological examination confirmed it as distant metastasis from cervical adenocarcinoma, ultimately leading to a diagnosis of pT1N1M1 (IVB stage) cervical cancer. Following a six-cycle treatment regimen with cadonilimab, paclitaxel, and cisplatin, the lymph nodes in the neck demonstrated a significant reduction, indicating a preliminary positive response. In this case, SMARCA4-deficient cervical adenocarcinoma was characterized by significantly high invasive potential, early metastasis, and heterogeneity, indicating the significance of early detection and molecular pathological diagnosis in guiding personalized treatment strategies. Immunotherapy combined with chemotherapy may offer a new therapeutic approach for this rare type of cancer.

Survival outcomes of lymph node dissection in early-stage epithelial ovarian cancer: identifying suitable candidates

The study aimed to assess the effect of lymph node dissection on survival outcomes in patients presenting with early-stage epithelial ovarian cancer and to delineate patient characteristics that may indicate a greater benefit from pelvic lymph node dissection. A retrospective analysis was performed on individuals diagnosed with clinical stage I-II epithelial ovarian cancer who received primary cytoreductive surgery at the Cancer Hospital Affiliated with Harbin Medical University from January 1, 2010, to January 1, 2018. The investigation encompassed an examination of demographic data, clinicopathological profiles, perioperative complications, and survival outcomes. A total of 315 patients diagnosed with ovarian cancer were incorporated into the study and were segregated into two distinct cohorts: 217 patients who underwent lymphadenectomy (Group A) and 98 patients who did not undergo the procedure (Group B). The disparities in progression-free survival and overall survival between the two cohorts did not attain statistical significance (p > 0.05). Upon conducting a subgroup analysis, it was discerned that patients characterized by clear cell carcinoma as the pathological subtype demonstrated a significantly extended progression-free survival post-lymphadenectomy (p = 0.02). Additionally, the operative duration for the patients in Group A was significantly protracted in comparison to Group B (146.15 ± 39.132 min vs. 133.49 ± 35.308 min, P = 0.043). For patients with early-stage ovarian cancer, lymph node dissection does not significantly improve progression-free or overall survival rates. Our findings suggest that individuals with clear cell carcinoma pathology have a higher probability of benefiting in terms of survival following lymph node dissection.

Impact of PARP inhibitors on progression-free survival in platinum-sensitive recurrent epithelial ovarian cancer: a retrospective analysis

Poly (ADP-ribose) polymerase (PARP) inhibitors such as olaparib and niraparib have shown promise in extending progression-free survival (PFS) in patients with platinum-sensitive recurrent (PSR) epithelial ovarian cancer. In this retrospective study, we aimed to present our own data on the effect of PARP inhibitors on PFS in recurrent epithelial ovarian cancer. 82 patients diagnosed with PSR epithelial ovarian, tubal, or primary peritoneal cancer between May 2017 and September 2023 were initially enrolled from our hospital. However, 16 patients had prior exposure to PARP inhibitors during primary treatment, and 11 were lost to follow-up. Consequently, the study focused on 55 eligible patients. PFS was compared between patients receiving PARP inhibitor maintenance therapy and those who did not. Among the 55 patients with PSR epithelial ovarian cancer, 18 received olaparib as maintenance therapy, 19 received niraparib, and 18 opted for observation. PARP inhibitor therapy significantly extended PFS (mean 24.0 months) compared to observation (mean 9.0 months, p = 0.0005), regardless of BRCA mutation status (HR = 0.20, 95% CI: 0.08-0.50). Subgroup analysis showed no statistical difference between olaparib and niraparib. Additionally, there was no PFS difference based on BRCA mutation status within both PARP inhibitor groups. Our retrospective study demonstrates that PARP inhibitor maintenance therapy, including olaparib and niraparib, significantly prolongs PFS in patients with PSR epithelial ovarian, tubal, or primary peritoneal cancer, These findings support the broad utilization of PARP inhibitors as a standard maintenance therapy for PSR epithelial ovarian cancer irrespective of BRCA mutation status.

Development and validation of a nomogram for predicting outcomes in ovarian cancer patients with liver metastases

To develop and validate a nomogram for predicting the overall survival (OS) of ovarian cancer patients with liver metastases (OCLM). This study identified 821 patients in the Surveillance, Epidemiology, and End Results (SEER) database. All patients were randomly divided in a ratio of 7:3 into a training cohort (n = 574) and a validation cohort (n = 247). Clinical factors associated with OS were assessed using univariate and multivariate Cox regression analyses, and backward stepwise regression was applied using the Akaike information criterion (AIC) to select the optimal predictor variables. The nomogram for predicting the OS of the OCLM patients was constructed based on the identified prognostic factors. Their prediction ability was evaluated using the concordance index (C-index), receiver operating characteristic (ROC) curve, calibration curve, and decision curves analysis (DCA) in both the training and validation cohorts. We identified factors that predict OS for OCLM patients and constructed a nomogram based on the data. The ROC, C-index, and calibration analyses indicated that the nomogram performed well over the 1, 2, and 3-year OS in both the training and validation cohorts. Additionally, in contrast to the External model from multiple perspectives, our model shows higher stability and accuracy in predictive power. DCA curves, NRI, and IDI index demonstrated that the nomogram was clinically valuable and superior to the External model. We established and validated a nomogram to predict 1,2- and 3-year OS of OCLM patients, and our results may also be helpful in clinical decision-making.

Time to death from cervical cancer and its predictors in hospitalized patients: a survival approach study in Mato Grosso, Brazil

Abstract Background Cervical cancer (CC) is a serious public health concern, being the fourth most common cancer among women and a leading cause of cancer mortality. In Brazil, many women are diagnosed late, and in Mato Grosso, with its geographical diversity, there are specific challenges. This study analyzed hospital survival and its predictors using data from the Hospital Information System (SIH) of the Unified Health System (SUS) in Mato Grosso from 2011 to 2023. Methods Cox regression and Kaplan-Meier models were applied to determine survival time and identify mortality predictors. The adjusted Hazard Ratio (AHR) with a 95% Confidence Interval (CI) was used to measure the association between the factors analyzed. Results The hospital mortality rate was 9.88%. The median duration of hospitalization was 33 days (interquartile range [IQR]: 12–36), with a median survival of 43.7%. Patients were followed up for up to 70 days. In the multivariable Cox model, after adjusting for potential confounders, the risk of death during hospitalization was higher in patients aged 40–59 years (AHR = 1.39, p = 0.027) and 60–74 years (AHR = 1.54, p = 0.007), in the absence of surgical procedures (AHR = 4.48, p &lt; 0.001), in patients with medium service complexity (AHR = 2.40, p = 0.037), and in the use of ICU (AHR = 4.97, p &lt; 0.001). On the other hand, patients with hospital expenses above the median (152.971 USD) showed a reduced risk of death (AHR = 0.21, p &lt; 0.001). Conclusion This study highlights that hospitalized CC patients have reduced survival, underscoring the need for interventions to improve care, including strategies for early diagnosis and expanded access to adequately resourced health services.

Management strategy for children with ovarian immature teratoma: results from a tertiary pediatric oncology center

Abstract Objectives We present an Egyptian study on pediatric ovarian immature teratomas (ITs), aiming to clarify our treatment strategy selection. Methods A retrospective review of all children with pure ovarian ITs who were treated at our institution between 2008 and 2023. The analysis included clinical characteristics, tumor staging according to Children’s Oncology Group (COG), grading based on the Norris system, management, and outcomes. Results Thirty-two patients were included, with a median age of 9 years. All patients underwent primary surgery. Unilateral salpingo-oophorectomy was performed in 31 patients. Surgical staging was completed in all patients. Based on COG staging, there were 28 patients (87.5%) stage I, 1 (3%) stage II, and 3 (9.5%) stage III. According to Norris classification, 16 patients (50%) were classified as grade I, 9 (28%) grade II, and 7 (22%) grade III. All patients in stage I were treated using surgery-alone approach, whereas the remaining four (12.5%) received adjuvant chemotherapy. Five patients in stage I had gliomatosis peritonei (GP), and none of them underwent extensive surgery. At a median follow-up of 86 months, two patients had events. The first patient (stage III/grade I) developed IT relapse on the operative bed, and the second (stage I/grade I) had a metachronous IT on the contralateral ovary. Both patients were successfully managed with surgery followed by second-line chemotherapy. Five-year overall survival and event-free survival for all patients were 100% and 93.4%, respectively. Conclusions Surgery-alone strategy with close follow-up achieves excellent outcomes for localized ovarian ITs in children, irrespective of the Norris grading or the presence of GP. However, adjuvant chemotherapy is questionable for patients with incompletely resected or locally advanced tumors, and its role requires further evaluation through prospective multicentric studies with a larger sample size.

Comparing survival outcomes between surgical and non-surgical treatments in patients with early-onset endometrial cancer and developing a nomogram to predict survival: a study based on Eastern and Western data sets

Abstract Background Surgery is the preferred approach for treating endometrial cancer (EC). However, the prognosis of young women undergoing surgery has not been thoroughly evaluated. This study aims to establish a prognostic nomogram for predicting overall survival (OS) in postoperative patients with early-onset endometrial cancer (EOEC), facilitating risk stratification for high-risk patients. Methods Patients diagnosed with EOEC during 2004–2015 were extracted from the Surveillance, Epidemiology, and End Results (SEER) database. The nomogram of OS was established according to the multivariate Cox regression analyses. The prediction accuracy and clinical net benefit of the model were assessed by the concordance index (C-index), receiver operating characteristic (ROC) curves, calibration plots, and decision curve analysis (DCA). Additionally, external validation was performed with 230 EOEC patients who underwent primary surgical treatment at the First Affiliated Hospital of Chongqing Medical University from 2013 to 2018. Results The mean survival period in the surgical group of EOEC was 87.62 months (range: 86.92–88.32), compared to 64.00 months (range: 55.05–72.96) in the non-surgical group. Compared with the non-surgical group, patients who underwent surgery had better outcomes. A total of 4345 eligible postoperative patients with EOEC were identified and enrolled in this study. Multivariate Cox analysis showed that age, race, grade, T stage, tumor size, and lymphadenectomy were significantly associated with the prognosis of EOEC, which were further incorporated to construct a nomogram. C-index and DCA showed the predictive capability and the clinical applicability of the nomogram was superior over the TNM stage and SEER stage. Furthermore, the external validation using the FAHCQMU cohort consistently demonstrated good predictive accuracy. Conclusions Generally, we developed a novel nomogram model by comprehensively integrating multiple risk factors, which accurately predicts the clinical prognosis of EOEC patients after surgery.

Prevalence of occult endometrial carcinoma in patients with endometrial intraepithelial neoplasia who underwent hysterectomy

To determine the prevalence of occult endometrial carcinoma in patients with endometrial intraepithelial neoplasia (EIN) post-hysterectomy and identify pre-hysterectomy risk factors predictive of occult carcinoma. This retrospective study included patients diagnosed with EIN between 2007 and 2021 who underwent hysterectomy as primary treatment. An expert gynecologic pathologist reviewed pathological slides. Data collected from medical records included demographic and gynecologic information, sonographic findings, and surgical and pathological outcomes. The prevalence of occult endometrial carcinoma was calculated. Descriptive statistics evaluated carcinoma incidence, and logistic regression analysis identified independent risk factors. A total of 113 patients were evaluated. The median time to hysterectomy was 9.1 weeks (range 5.8-12.8 weeks). Post-hysterectomy, 36 patients (31.8%) were diagnosed with endometrial carcinoma, all endometrioid type. Of these, 88.9% were stage I per the International Federation of Gynecology and Obstetrics classification system, and 11.1% were at high risk for nodal metastasis. Predictive factors for occult carcinoma included the intraoperative gross lesion size (2 cm or larger and less than 2 cm) and endometrial aspiration. Adjusted odds ratios were 6.723 (95% CI 2.338 to 19.333) for lesions 2 cm or larger, 3.381 (95% CI 1.128 to 10.132) for lesions less than 2 cm, and 2.752 (95% CI 1.092 to 6.936) for endometrial aspiration. Occult endometrial carcinoma was identified in 31.8% of patients with a pre-hysterectomy EIN diagnosis. The significant predictors were endometrial aspiration and the presence of a gross lesion during surgery.

CT-based body composition analysis to study the effect of visceral obesity on postoperative complications in ovarian cancer: implications for young patients

Ovarian cancer is characterized by high morbidity and mortality, with surgery remaining the primary treatment modality. The occurrence of postoperative complications significantly impacts patient prognosis and quality of life. As cancer increasingly affects younger individuals, it is crucial to consider age-related differences. Meanwhile, epidemiology suggests a high prevalence of obesity among females. This study aims to evaluate the effect of visceral obesity (VO), diagnosed using computed tomography (CT)-based body composition analysis, on postoperative complications. A total of 309 patients operated between 2017 and 2022 were included in this study. Patients were stratified into two age groups: ≤65 years (younger group) and > 65 years (older group). The receiver operating characteristic (ROC) curve was employed to determine the threshold value for VO. Univariate and multivariate analyses were conducted to identify risk factors associated with postoperative complications. According to the cut-off value, the incidence of postoperative complications was significantly higher in younger patients with VO compared to the non-VO group (56% vs. 36%, p < 0.01), whereas no difference was observed in older age groups. VO (OR = 1.980, p = 0.031), total protein < 65 g/L (OR = 3.704, p = 0.045), primary debulking surgery (PDS) (OR = 0.369, p = 0.026), duration of surgery (OR = 1.004, p = 0.006) and intraoperative bleeding volume (OR = 1.003, p < 0.01) were identified as independent predictors of postoperative complications in the younger age group. International Federation of Gynecology and Obstetrics (FIGO) stage for III or IV (OR = 4.00, p = 0.029) remained as the only independent predictor for the older age group. In young ovarian cancer patients, VO may serve as a predictor for postoperative complications, and appropriate preventive measures may be beneficial in reducing the incidence of postoperative complications.

Introduction of gasless laparoscopic surgery as a minimally invasive procedure for endometrial cancer and its usefulness from the viewpoint of the learning curve

Abstract Background We investigated the usefulness of gasless laparoscopic surgery (GLS) using a subcutaneous abdominal wall lifting method for endometrial cancer. Methods We studied 105 patients with early endometrial cancer who underwent GLS (55) or open surgery (50). A uterine manipulator was used in all GLS cases. We compared operative time, blood loss, number of lymph nodes removed, hospital stay, perioperative complications, cases converted to laparotomy, and recurrence and survival rates. We also studied the learning curve and proficiency of GLS. Results The GLS group had significantly longer operative time (265 vs. 191 min), reduced blood loss (184 vs. 425 mL), shorter hospital stay (9.9 vs. 17.6 days), and fewer postoperative complications (1.8 vs. 12.0%) than the open group. No case was converted to laparotomy. Disease-free and overall survival rates at 4 years postoperatively (GLS vs. open groups) were 98.0 versus 97.8 and 100 versus 95.7%, respectively, and there was no significant difference between the groups. Regarding the learning curve for GLS, two different phases were observed in approximately 10 cases. Operator 2, who was not accustomed to laparoscopic surgery, showed a significant reduction in operative time in the later phase 2. Conclusions GLS for endometrial cancer results in less bleeding, shorter hospital stay, and fewer complications than open surgery. Recurrence and survival rates were not significantly different from those of open surgery. This technique may be introduced in a short time for operators who are skilled at open surgery but not used to laparoscopic surgery.

Primary endometrioid carcinoma of the uterosacral ligament arising from deep infiltrating endometriosis 6 years after bilateral salpingo-oophorectomy due to atypical proliferative endometrioid tumor of the ovary: a rare case report

Abstract Background Endometriosis can potentially lead to the development of a malignant tumor. Most malignant tumors arising from the endometriosis originate from the ovarian endometrioma, whereas those arising from extragonadal lesions are rare. We report a rare case of endometrioid carcinoma that developed from deep infiltrating endometriosis in the uterosacral ligament 6 years after treatment for atypical proliferative endometrioid tumor of the ovary in a 48-year-old woman. Case presentation Six years ago, the patient underwent laparoscopic bilateral salpingo-oophorectomy for her right ovarian tumor with atypical proliferative (borderline) endometrioid tumor accompanied by ovarian endometrioma. The solid tumor in the cul-de-sac was detected during follow-up using magnetic resonance imaging. Positron emission tomography/computed tomography revealed an abnormal accumulation of 18 F-fluorodeoxyglucose at the tumor site. Thus, tumor recurrence with borderline malignancy was suspected. The patient underwent diagnostic laparoscopy followed by hysterectomy and partial omentectomy. Retroperitoneal pelvic lymphadenectomy and para-aortic lymphadenectomy were also performed. The cul-de-sac tumor at the left uterosacral ligament was microscopically diagnosed as invasive endometrioid carcinoma arising from deep infiltrating endometriosis. The final diagnosis was primary stage IIB peritoneal carcinoma. The patient received six courses of monthly paclitaxel and carboplatin as adjuvant chemotherapy. The patient showed no evidence of recurrence for 2 years after the treatments. Conclusion This study reports a rare case of metachronous endometriosis-related malignancy that developed 6 years after treatment for borderline ovarian tumor. If endometriosis lesions remain after bilateral salpingo-oophorectomy, the physician should keep the malignant nature of endometriosis in mind.

Diagnostic performance of intraoperative assessment in grade 2 endometrioid endometrial carcinoma

Abstract Background Endometrial carcinoma is the most common gynecologic malignancy in developed countries. Grade 2 carcinoma is associated with pelvic lymph-node metastasis, depending on selected risk factors. Intraoperative assessment (IOA) can identify patients at risk for lymph node metastasis who should undergo staging surgery. Our objective was to establish the diagnostic precision of IOA in determining the need for surgical staging in grade 2 endometrioid endometrial carcinoma. Methods Two hundred twenty-two patients underwent IOA. Results were compared to the final pathology report. The accuracy of the IOA parameters was calculated. Variables were evaluated in patients with positive versus negative IOA. Overall and disease-free survivals were calculated according to IOA, lymphadenectomy, and nodal metastasis. Results IOA was positive in 80 patients. It showed an accuracy of 76.13% when compared with the postoperative assessment. The best individual parameter was myometrial invasion. Nodal metastasis was observed in 16 patients in the positive IOA group and 7 patients in the negative group. Patients with lymph node metastasis had a 5-year overall survival rate of 80.9%, whereas patients without metastasis had a 5-year overall survival rate of 97.9%. Conclusions IOA is an adequate tool to identify high-risk patients in grade 2 endometrial carcinoma. Myometrial invasion is the individual parameter that yields the highest diagnostic precision.

Prognostic factors and treatment outcomes in female genital tract melanoma: a 10-year retrospective cohort study

To investigate the clinical characteristics and prognostic factors influencing overall survival (OS) in patients with primary female genital tract malignant melanoma (PFGMM). Methods Clinical data of 60 patients with PFGMM treated at Sichuan Cancer Hospital between 2014 and 2024 were retrospectively analyzed. Survival curves were plotted using the Kaplan-Meier method and compared with the log-rank test. Variables with a P value < 0.05 in univariate analysis were included in the multivariate Cox proportional hazards model to identify independent prognostic factors. Results The 1-, 3-, and 5-year OS rates of patients with PFGMM were 73.3%, 53.3%, and 16.7%, respectively, with a median survival of 25 months. Univariate analysis indicated that menopausal status, surgery, chemotherapy, immunotherapy, and post-treatment recurrence were significantly associated with OS (all P < 0.05). Multivariate analysis identified age ≥ 55 years, presence of chronic comorbidities, tumor located in the lower or middle genital tract, menopausal status, and absence of chemotherapy or immunotherapy as independent adverse prognostic factors (all P < 0.05). Conclusion PFGMM is a rare and aggressive malignancy with poor long-term survival. Older age, menopausal status, tumor site, and lack of systemic therapy were independently associated with worse prognosis. Comprehensive treatment, including surgery combined with chemotherapy and immunotherapy, may improve patient outcomes.

Clear cell carcinoma arising from abdominal wall endometriosis—a report on two cases and literature review

Abstract Background Malignant transformation of abdominal wall endometriosis is extremely rare. Clear cell carcinoma and endometrioid carcinoma are the two most prevalent histological subtypes of malignant endometriosis. To date, approximately, thirty cases of clear cell carcinoma arising from abdominal wall endometriosis have been described worldwide. Case presentation We report two cases of clear cell carcinoma developing postoperatively in the anterior abdominal wall in women with a history of extensive endometriosis. Histopathology of the resected abdominal wall tumor demonstrated benign endometriosis contiguous with features of clear cell carcinoma. These histological features satisfied Sampson’s criteria which are required for diagnosing malignant endometriosis. Both patients were successfully managed with platinum-based adjuvant chemotherapy following cytoreductive surgery. Conclusion Clear cell carcinoma arising from the abdominal wall endometriosis is a rare, highly aggressive cancer with a propensity to recur or metastasize. Due to the limited publications on this clinical entity, there are no clearly established protocols regarding adjuvant treatment, and an evaluation of prognostic factors is lacking. Clinicians must have a high index of suspicion for malignant endometriosis of the abdominal wall, particularly in patients with an abdominal wall mass, prior abdominal surgery, and long-standing endometriosis. By presenting our case, we expect to raise awareness and study of this rare endometriosis-related neoplasm.

Vaginal-assisted gasless laparoendoscopic single-site radical hysterectomy for early cervical cancer: a retrospective pilot study

Abstract Background Minimally invasive surgery for early cervical cancer is debated. We developed this new vaginal-assisted gasless laparoendoscopic single-site radical hysterectomy for early cervical cancer, and we aimed to evaluate the feasibility and safety of this surgical procedure and observe the early oncologic outcomes. Methods From January 2019 to August 2020, patients with early cervical cancer who underwent vaginal-assisted gasless laparoendoscopic single-site radical hysterectomy were studied retrospectively. The clinical characteristics, pathologic outcomes, perioperative outcomes, and follow-up details of the patients were recorded. Results Forty-eight patients underwent vaginal-assisted gasless laparoendoscopic single-site radical hysterectomy were included, 14 (29.2%) with stage IB1, 13 (27.1%) with stage IB2, 7 (14.6%) with stage IB3, 10 (20.8%) with stage IIA1, and 4 (8.3%) stage with IA2. The mean age at diagnosis was 50.4 (range 28–72) years old. The mean operative time was 237.3 min (range 162–393), and the mean estimated blood loss was 246.5 ml (range 80–800). No intraoperative complications occurred, and there were no patients who were readmitted. Histological types were distributed as follows: squamous cell carcinoma 72.9%, adenocarcinoma 10.4%, and adenosquamous cell carcinoma 16.7%. There were 2 patients (4.2%) with positive nodes, 20 patients (41.7%) with positive lymphovascular space invasion, and 2 patients (4.2%) with positive parametria. Twenty-eight patients (58.3%) received adjuvant therapy after the operation. With a mean follow-up of 17.7 months (range 6–26), there were no recurrent cases, and 11 patients (22.9%) suffered lower limb lymphoedema. Conclusions The vaginal-assisted gasless laparoendoscopic single-site radical hysterectomy might be a feasible technique for early cervical cancer, with promising short-term oncological outcomes and safety. A prospective study with more patients and longer follow-up periods should be performed to further evaluate the safety and oncological outcomes.

Outcome quality standards in advanced ovarian cancer surgery

Abstract Introduction Advanced ovarian cancer surgery (AOCS) frequently results in serious postoperative complications. Because managing AOCS is difficult, some standards need to be established that allow surgeons to assess the quality of treatment provided and consider what aspects should improve. This study aimed to identify quality indicators (QIs) of clinical relevance and to establish their acceptable quality limits (i.e., standard) in AOCS. Materials and methods We performed a systematic search on clinical practice guidelines, consensus conferences, and reviews on the outcome and quality of AOCS to identify which QIs have clinical relevance in AOCS. We then searched the literature (from January 2006 to December 2018) for each QI in combination with the keywords of advanced ovarian cancer, surgery, outcome, and oncology. Standards for each QI were determined by statistical process control techniques. The acceptable quality limits for each QI were defined as being within the limits of the 99.8% interval, which indicated a favorable outcome. Results A total of 38 studies were included. The QIs selected for AOCS were complete removal of the tumor upon visual inspection (complete cytoreductive surgery), a residual tumor of &lt; 1 cm (optimal cytoreductive surgery), a residual tumor of &gt; 1 cm (suboptimal cytoreductive surgery), major morbidity, and 5-year survival. The rates of complete cytoreductive surgery, optimal cytoreductive surgery, suboptimal cytoreductive surgery, morbidity, and 5-year survival had quality limits of &lt; 27%, &lt; 23%, &gt; 39%, &gt; 33%, and &lt; 27%, respectively. Conclusion Our results provide a general view of clinical indicators for AOCS. Acceptable quality limits that can be considered as standards were established.

Nadir CA-125 serum levels during neoadjuvant chemotherapy and no residual tumor at interval debulking surgery predict prognosis in advanced stage ovarian cancer

AbstractBackgroundRecent phase III randomized trials have suggested that neoadjuvant chemotherapy followed by interval debulking surgery (NACT-IDS) is a treatment option for patients with advanced epithelial ovarian cancer. This study aimed to use CA-125 and computed tomography (CT) scanning to generate a simple and clinically applicable model of predicting complete cytoreduction by interval debulking surgery (IDS) and the overall survival in patients who receive taxane/platinum-based chemotherapy as neoadjuvant chemotherapy (NACT).MethodsPatients with stage IIIc or IV epithelial ovarian cancer who underwent taxane/platinum-based NACT followed by IDS in Gunma Prefectural Cancer Center, Takasaki General Medical Center, and Gunma University from April 2009 to March 2015 were included. Patients underwent a CT scan to confirm confirm tumors unresectable by standard surgery before NACT. CA-125 levels were measured pre-NACT, after each cycle of NACT, and before IDS. CT was also performed before IDS to evaluate tumor metastasis. Data were collected retrospectively and analyzed to determine the predictive factors of complete resection and overall survival.ResultsAmong 63 patients who received NACT-IDS, 43 and 20 patients had stages IIIc and IV epithelial ovarian cancer at diagnosis, respectively. CT predictors of residual tumors after IDS such as extra-ovarian implants (P= 0.009) and omental cakes (P= 0.038) were not present. Univariate analysis revealed that the independent factors for overall survival were no residual tumor by IDS (P= 0.0016) and CA125 ≤ 20 U/ml before IDS (P= 0.0011).ConclusionsAlthough this study had a small sample size, NACT-IDS used to completely remove macroscopic disease which significantly improved the prognosis of patients with preoperative CA-125 ≤ 20 U/ml. Results from this study provide useful information for future studies on the management of patients with advanced epithelial ovarian cancer.

The efficacy and safety of the addition of poly ADP-ribose polymerase (PARP) inhibitors to therapy for ovarian cancer: a systematic review and meta-analysis

Abstract Background The purpose of this study was to explore the efficacy and tolerability of poly ADP-ribose polymerase (PARP) inhibitors in patients with ovarian cancer. Methods The meta-analysis searched the PubMed, Web of Science, EBSCO, and Cochrane libraries from inception to February 2020 to identify relevant studies. And the main results of this study were long-term prognosis and treatment-related adverse events. Results The results showed that the addition of PARP inhibitors could significantly prolong progression-free survival (PFS) and overall survival (OS) for patients with ovarian cancer (HR 0.44, 95% CI 0.34–0.53, p &lt; 0.001; HR, 0.79, 95% CI 0.65–0.94, p &lt; 0.001, respectively). In the BRCA 1/2 mutation patients, the HR of PFS was 0.29 (p &lt; 0.001), and the HR was 0.51 (p &lt; 0.001) in the no BRCA 1/2 mutation patients. The HR of PFS was 0.40 (p &lt; 0.001) in the homologous recombination deficiency (HRD) mutation patients, while the HR was 0.80 (p &lt; 0.001) in the no HRD mutation patients. Moreover, the analysis found that the use of PARP inhibitors did not significantly increase the risk of all grade adverse events (AEs) (RR = 1.04, p = 0.16). But the incidence of grade 3 or higher AEs was increased (RR = 1.87, p = 0.002). In general, the AEs were mainly manifested in the blood system. Conclusions PARP inhibitors can improve the prognosis of ovarian cancer patients with and without genetic mutations (BRCA 1/2 or HRD). Furthermore, PARP inhibitors were tolerable to patients when added to their current therapy, although it inevitably adds the grade 3 and higher AEs.

Surgical staging of apparent early-stage ovarian mucinous carcinoma

Abstract Objectives The aim of the study was to explore the rate of upstaging after complete surgical staging among patients with apparent FIGO stage I ovarian mucinous carcinoma. Methods Ovarian mucinous carcinoma patients with surgical treatment at the Peking Union Medical College Hospital between October 2020 and January 1994 were retrospectively reviewed. Results In total, 163 patients were included in this study. Surgical restaging was performed in 89 patients after initial incomplete surgical staging, and one-step complete surgical staging was performed in 74 patients. Among these initially incompletely staged patients, residual tumors were found in 16 patients (16/89, 17.9%). Among the 19 patients with apparent FIGO stage IA, no patient was found to have residual tumors after incomplete staging surgery, according to the final pathology result of restaging surgery. Ovarian cystectomy (OR=4.932, 95% CI= 1.347–18.058, P=0.016) was an independent risk factor for residual tumors after incomplete staging surgery. Among all 163 patients, upstaging occurred in 15 patients (15/163, 9.2%). Among 44 apparent FIGO stage IA patients, no patient was upstaged to FIGO II–IVB. Moreover, both a history of ovarian mucinous tumor (OR=4.745, 95% CI= 1.132–19.886, P=0.033) and bilateral ovary involvement (OR=9.739, 95% CI= 2.016–47.056, P=0.005) were independent risk factors for upstaging to FIGO stage II–IVB. Conclusions For patients with apparent FIGO stage IA disease, the possibility of residual tumors and upstaging is relatively low. For patients with cystectomy, bilateral mucinous carcinomas, or a history of ovarian mucinous tumors, complete staging surgery maintains greater significance.

Assessment of galectins -1, -3, -4, -8, and -9 expression in ovarian carcinoma patients with clinical implications

AbstractBackground and aimGalectins have been recently tackled by many researchers in the field of cancer due to their role in tumorigenesis, disease progression, and metastasis. Thus, they are currently involved in biomarkers research on several types of cancer. In ovarian cancers, few studies were carried out to evaluate galectins expression profiling. Hence, our present study was executed to evaluate the mRNA expression of galectins -1, -3, -4, -8, and -9 in epithelial ovarian cancers.MethodsFifty-six tumor samples of ovarian carcinomas were analyzed for mRNA expression using qRT-PCR, and fold-changes were calculated in comparison to tissue samples of 26 women with normal ovaries.ResultsThe results of the present paper emphasize the importance of galectins as predictors for targeted therapy.LGALS1,LGALS3,LGALS4,LGALS8, andLGALS9were found to be mostly overexpressed in ovarian carcinoma patients with the following percentage: 78.6%, 92.9%, 66.1%, 87.5%, and 85.7% respectively. Moreover, galectins -3 and -9 were found to be significantly elevated with lymph node metastasis (p= 0.044 andp= 0.011). Also, upregulation of galectin-1 and -9 were statistically significant in stages IIB, IIC, and IIIB (p= 0.002) in FIGO staging. CA19.9 is positively correlated to galectin-4 expression (p= 0.039).ConclusionOur findings strengthen the role of galectins in carcinogenesis, disease progression, and lymphnode metastasis in ovarian carcinomas. And since these galectins are mostly overexpressed, they could be promising markers for targeted therapy to reduce disease progression and metastasis process.

Tubo-ovarian mass with raised CA-125 in a 21-year-old female

Abstract Introduction Peritonitis associated with fungal species Curvularia lunata seldom occurs with only five cases reported in the literature, all in middle-age patients with comorbidities undergoing dialysis. Case report A 21-year-old female who was referred to surgical oncology OPD with a diagnosis of ovarian malignancy, based on raised cancer antigen 125 (CA 125) and suspected tubo-ovarian mass (TOM) on magnetic resonance imaging (MRI). A review of the MRI showed a pelvic collection with TOM, suggestive of infective pathology. Fungal culture and mass spectroscopy of the cystic collection identified the presence of Curvularia lunata. She was treated with oral itraconazole which showed symptomatic improvement and radiological response. In the follow-up period, the patient developed chest wall swelling, aspiration and geneXpert® revealed multidrug-resistant (MDR) tuberculosis, and treatment was started. Conclusions Unusual causes of TOM and raised CA 125 should be kept in mind when dealing with young patients, as the possibility of epithelial ovarian cancer in this age is very low.

Effect of bevacizumab combined with chemotherapy on SDF-1 and CXCR4 in epithelial ovarian cancer and its prognosis

Abstract Background The effect of bevacizumab combined with chemotherapy on the expression of stromal cell-derived factor-1 (SDF-1) and receptor CXCR4 in epithelial ovarian cancer tumor cells and its prognosis are unknown. Our work aimed to investigate the effect of chemotherapy +/− bevacizumab on these markers and the impact of this treatment modality in clinical outcomes. Methods Altogether 68 patients with epithelial ovarian cancer who were treated with chemotherapy in our hospital from June 2018 to June 2019 were selected. It was an open-labeled and controlled clinical trial (ethical approval no. 20180435). The patients were grouped according to their admission order. Patients treated with paclitaxel and carboplatin were included in group A, while patients treated with bevacizumab, paclitaxel, and carboplatin were included in group B. qRT-PCR was used to detect the changes of SDF-1 and CXCR4 before and after chemotherapy. Various clinical indicators of patients in the two groups were recorded to analyze the clinical efficacy, and safety of different treatment modalities and the prognosis of the two groups was analyzed. Results The relative expression of SDF-1 and CXCR4 was positively correlated with epithelial ovarian cancer stages (P&lt;0.00). Together, SDF-1 and CXCR4 were positively correlated in epithelial ovarian cancer staging (P&lt;0.001). SDF-1 and CXCR4 in both groups after chemotherapy were significantly decreased (P&lt;0.001), and the downregulation of SDF-1 and CXCR4 expression in group B was significantly higher than that in group A after chemotherapy (P&lt;0.001). No significant difference in the metastasis rates of the two groups before chemotherapy was observed (P&gt;0.05), but the recurrence rate after 1 year was lower in group B than in group A (P&lt;0.05). Conclusion Adding bevacizumab diminished the expression of related cancer markers SDF-1 and CXCR4 more than chemotherapy alone in patients with epithelial ovarian cancer. Furthermore, better rates of recurrence with no concerns regarding adverse drug reactions or quality of life were seen in bevacizumab plus chemotherapy group.

Impact of prehabilitation during neoadjuvant chemotherapy and interval cytoreductive surgery on ovarian cancer patients: a pilot study

Abstract Background Cytoreductive surgery followed by systemic chemotherapy is the standard of treatment in advanced ovarian cancer where feasible. Neoadjuvant chemotherapy (NACT) followed by surgery is applicable where upfront cytoreductive surgery is not feasible because of few certain reasons. Nevertheless, surgical interventions and the chemotherapy itself may be associated with postoperative complications usually entailing slow postoperative recovery. Prehabilitation programs consist of the patient’s preparation before surgery to improve the patient’s functional capacity. The aim of this study was to evaluate the impact of a prehabilitation program during neoadjuvant treatment and interval cytoreductive surgery for ovarian cancer patients. Methods A retrospective observational pilot study of patients with advanced ovarian cancer treated with NACT and interval cytoreductive surgery was conducted. The prehabilitation group received a structured intervention based on physical exercise, nutritional counseling, and psychological support. Nutritional parameters were assessed preoperatively and postoperatively, and functional parameters and perioperative and postoperative complications were also recorded. Results A total of 29 patients were included in the study: 14 in the prehabilitation group and 15 in the control group. The patients in the prehabilitation program showed higher mean total protein levels in both preoperative (7.4 vs. 6.8, p = 0.004) and postoperative (4.9 vs. 4.3, p = 0.005) assessments. Up to 40% of controls showed intraoperative complications vs. 14.3% of patients in the prehabilitation group, and the requirement of intraoperative blood transfusion was significantly lower in the prehabilitation group (14.3% vs. 53.3%, p = 0.027). The day of the first ambulation, rate of postoperative complications, and length of hospital stay were similar between the groups. Finally, trends towards shorter time between diagnosis and interval cytoreductive surgery (p = 0.097) and earlier postoperative diet restart (p = 0.169) were observed in the prehabilitation group. Conclusion Prehabilitation during NACT in women with ovarian cancer candidates to interval cytoreductive surgery may improve nutritional parameters and thereby increase postoperative recovery. Nevertheless, the results of this pilot study are preliminary, and further studies are needed to determine the clinical impact of prehabilitation programs.

MiR-125 inhibited cervical cancer progression by regulating VEGF and PI3K/AKT signaling pathway

Abstract Background MiR-125 has been shown to be involved in a variety of cancers, including cervical cancer (CC). Here, our goal was to explore miR-125 functional role and molecular mechanism in cervical cancer development and progression. Methods qRT-PCR was employ to detect miR-125 and VEGF mRNA expression. Western blot was applied for testing protein levels (VEGF, E-cadherin, N-cadherin, vimentin, AKT, p-AKT, PI3K, and p-PI3K). MTT and transwell assays were used for detecting cervical cancer cell progression, including cell viability, migration, and invasion. Results We observed that miR-125 was downregulated, whereas VEGF was upregulated in cervical cancer tissues and cell lines (CaSki and SiHa). MiR-125 inhibited the proliferation, invasion, and migration by targeting VEGF in cervical cancer. Moreover, miR-125 negatively regulated VEGF expression in cervical cancer tissues. Finally, we demonstrated that miR-520d-5p inhibited the activation of PI3K/AKT signaling pathway. Conclusion In conclusion, the findings demonstrated that miR-125 inhibited cervical cancer progression and development by suppression VEGF and PI3K/AKT signaling pathway.

Prognostic and clinicopathological significance of C-reactive protein in patients with ovarian cancer: a meta-analysis

Abstract Background Many studies have explored the relationship between C-reactive protein (CRP) levels and survival outcomes in patients with ovarian cancer (OC); however, consistent results have not been reported. As such, this meta-analysis was performed to accurately assess the prognostic and clinicopathological roles of CRP in OC. Methods The PubMed, Web of Science, Embase, and Cochrane Library databases were systematically searched for relevant studies published from inception to April 7, 2023. The effect of CRP level(s) and OC prognostic outcomes was analyzed by computing the combined hazard ratio (HR) and corresponding 95% confidence interval (CI). Thereafter, the association between CRP level(s) and clinicopathological factors was evaluated using a combined odds ratio (OR) and corresponding 95% CI. Results The present meta-analysis included 15 studies comprising 3202 subjects. According to the combined data, higher CRP levels were markedly associated with unfavorable overall survival (OS) (HR 1.23 [95% CI 1.11–1.37]; p &lt; 0.001) and progression-free survival (PFS) (HR 1.55 [95% CI 1.30–1.84]; p &lt; 0.001) in patients with OC. Furthermore, the results indicated that high CRP levels were significantly correlated with International Federation of Gynecology and Obstetrics (FIGO) stages III–IV (p &lt; 0.001), residual tumor size ≥ 1 cm (p &lt; 0.001), histological grade 3 (p = 0.040), and ascites volume ≥ 500 mL (p &lt; 0.001). Conclusion The results of this meta-analysis demonstrated that higher serum CRP levels were strongly associated with dismal OS and PFS in subjects with OC. High CRP levels were also significantly associated with clinical factors implicated in tumor aggressiveness and the development of OC.

Association of three micro-RNA gene polymorphisms with the risk of cervical cancer: a meta-analysis and systematic review

Abstract Objective Regulation of single nucleotide polymorphisms (SNP) in micro-RNA (miRNA) on the host cells may be one of the most important factors influencing the occurrence of cervical cancer based on the prevalence of HPV infection and the development of cervical cancer. In order to explore the contribution of miRNA polymorphism to the occurrence and development of cervical cancer, we conducted an analytical study. Methods We selected the polymorphisms of three widely studied miRNAs (miRNA-146a rs2910164, miRNA-499 rs3746444, and miRNA-196a2 rs11614913). Then, we conducted a meta-analysis (for the first time) to investigate their susceptibility to cervical cancer. Case control studies on the correlation between these three miRNAs and cervical cancer susceptibility were investigated by searching on from Pubmed, The Cochrane Library, Embase, CBM, CNKI, Wanfang database, and VIP database. Basic characteristics were recorded and meta-analysis of the case studies was performed using the STATA 15.1 software. Results The miRNA-146a rs2910164 mutation significantly reduced the risk of cervical cancer in both recessive model (OR = 0.804, 95% CI = 0.652-0.992, P = 0.042; CC vs. CG+GG) and allelic model (OR = 0.845, 95% CI = 0.721-0.991, P = 0.038; C vs. G). There was no significant correlation between miRNA-499 rs3746444 and the risk of cervical cancer. The miRNA-196a2 rs11614913 mutation was significantly associated with a reduced risk of cervical cancer in homozygous model (OR = 0.641, 95% CI = 0.447-0.919, P = 0.016; TT vs. CC), dominant model (OR = 0.795, 95% CI = 0.636-0.994, P = 0.045; CT+TT vs. CC), recessive model (OR = 0.698, 95% CI = 0.532-0.917, P = 0.01; TT vs. CC+CT), and allelic models (OR = 0.783, 95% CI = 0.643-0.954, P = 0.015, T vs. C). Conclusion In summary, this meta-analysis shows that the mutant genotypes of miRNA-146a rs2910164 and miRNA-196a2 rs11614913 are associated with a reduced risk of cervical cancer. Therefore, they may be two gene regulatory points for the prevention of cervical cancer. Systematic review registration PROSPERO registration number CRD42021270079.

Fertility-sparing uterine displacement for pelvic malignancies: surgical options and radiotherapy dosimetry on a human cadaver

Abstract Background Radio(chemo)therapy is often required in pelvic malignancies (cancer of the anus, rectum, cervix). Direct irradiation adversely affects ovarian and endometrial function, compromising the fertility of women. While ovarian transposition is an established method to move the ovaries away from the radiation field, surgical procedures to displace the uterus are investigational. This study demonstrates the surgical options for uterine displacement in relation to the radiation dose received.  Methods The uterine displacement techniques were carried out sequentially in a human female cadaver to demonstrate each procedure step by step and assess the uterine positions with dosimetric CT scans in a hybrid operating room. Two treatment plans (anal and rectal cancer) were simulated on each of the four dosimetric scans (1. anatomical position, 2. uterine suspension of the round ligaments to the abdominal wall 3. ventrofixation of the uterine fundus at the umbilical level, 4. uterine transposition). Treatments were planned on Eclipse® System (Varian Medical Systems®,USA) using Volumetric Modulated Arc Therapy. Data about maximum (Dmax) and mean (Dmean) radiation dose received and the volume receiving 14 Gy (V14Gy) were collected. Results All procedures were completed without technical complications. In the rectal cancer simulation with delivery of 50 Gy to the tumor, Dmax, Dmean and V14Gy to the uterus were respectively 52,8 Gy, 34,3 Gy and 30,5cc (1), 31,8 Gy, 20,2 Gy and 22.0cc (2), 24,4 Gy, 6,8 Gy and 5,5cc (3), 1,8 Gy, 0,6 Gy and 0,0cc (4). For anal cancer, delivering 64 Gy to the tumor respectively 46,7 Gy, 34,8 Gy and 31,3cc (1), 34,3 Gy, 20,0 Gy and 21,5cc (2), 21,8 Gy, 5,9 Gy and 2,6cc (3), 1,4 Gy, 0,7 Gy and 0,0cc (4). Conclusions The feasibility of several uterine displacement procedures was safely demonstrated. Increasing distance to the radiation field requires more complex surgical interventions to minimize radiation exposure. Surgical strategy needs to be tailored to the multidisciplinary treatment plan, and uterine transposition is the most technically complex with the least dose received.

Prognostic significance of lymphovascular space invasion in early-stage low-grade endometrioid endometrial cancer: a fifteen-year retrospective Chinese cohort study

Abstract Objective In 2016, the ESMO-ESGO-ESTRO consensus included LVSI (Lymph-vascular space invasion, LVSI) status as a risk stratification factor for stage I endometrioid endometrial cancer (EEC) patients and as one of the indications for adjuvant therapy. Furthermore, LVSI is included in the new FIGO staging of endometrial cancer (EC) in 2023. However, the data contribution of the Chinese population in this regard is limited. The present study aimed to further comfirm the influence of LVSI on the prognosis of early-stage low-grade EEC in a fifteen-year retrospective Chinese cohort study. Methods This retrospective analysis cohort included 702 EEC patients who underwent TAH/BSO surgery, total abdominal hysterectomy, bilateral salpingooophorectomy in Peking University People’s Hospital from 2006 to 2020. Patients were stratified based on LVSI expression status as: LVSI negative group and LVSI positive group. Clinical outcome measures related to LVSI, assessed with a univariate and multivariate Cox proportional hazards regression model. Results 702 EEC patients with stage I and grade 1–2 were analyzed. 58 patients (8.3%) were LVSI-positive and 14 patients (2.0%) was relapse. Recurrence rates in LVSI-negative and LVSI-positive were 1.6% and 6.9%, respectively. 5-year disease-free survival (DFS) rate in LVSI-negative and LVSI-positive were 98.4% and 93.1%, respectively. These rates for 5-year overall (OS) survival in LVSI-negative were 98.9% while it was 94.8% in LVSI-positive. Multivariate analysis showed that LVSI is an independent risk factor for 5-year DFS (HR = 4.60, p = 0.010). LVSI has a similar result for 5-year OS(HR = 4.39, p = 0.028). Conclusions LVSI is an independent predictor of relapse and poor prognosis in early-stage low-grade endometrioid endometrial cancer in the Chinese cohort.

Oncological outcomes of fertility-sparing surgery versus radical surgery in stage - epithelial ovarian cancer: a systematic review and meta-analysis

Abstract Background The oncological outcomes of fertility-sparing surgery (FSS) compared to radical surgery (RS) in patients with stage I epithelial ovarian cancer (EOC) remain a subject of debate. We evaluated the risk ratios (RRs) for outcomes in patients with stage I EOC who underwent FSS versus RS. Methods We conducted a systematic search of PubMed, Web of Science, and Embase for articles published up to November 29, 2023. Studies that did not involve surgical procedures or included pregnant patients were excluded. We calculated the RRs for disease-free survival, overall survival, and recurrence rate. The quality of the included studies was assessed using the Cochrane Risk of Bias in Nonrandomized Studies of Interventions (ROBINS-I) tool. The meta-analysis was registered on PROSPERO (CRD42024546460). Results From the 5,529 potentially relevant articles, we identified 83 articles for initial screening and included 12 articles in the final meta-analysis, encompassing 2,906 patients with epithelial ovarian cancer. There were no significant differences between the two groups in disease-free survival (RR [95% confidence interval {CI}], 0.90 [0.51, 1.58]; P = 0.71), overall survival (RR [95% CI], 0.74 [0.53, 1.03]; P = 0.07), and recurrence rate (RR [95% CI], 1.10 [0.69, 1.76]; P = 0.68). In sensitivity analyses, the significant difference was observed only for overall survival (before exclusion: RR [95% CI], 0.74 [0.53–1.03], P = 0.07; after exclusion: RR [95% CI], 0.70 [0.50–0.99]; P = 0.04). Conclusions This is the first and only individual patient data meta-analysis comparing disease-free survival, overall survival, and recurrence rate of patients with early-stage epithelial ovarian cancer undergoing FSS and RS. FSS was associated with similar disease-free survival and risk of recurrence as RS. We hypothesized that the decreased overall survival in the FSS group could not be attributed to distant metastases from epithelial ovarian cancer.

Preoperative serum level of CA153 and a new model to predict the sub-optimal primary debulking surgery in patients with advanced epithelial ovarian cancer

Abstract Objective The aim of this study was to establish a preoperative model to predict the outcome of primary debulking surgery (PDS) for advanced ovarian cancer (AOC) patients by combing Suidan predictive model with HE4, CA125, CA153 and ROMA index. Methods 76 AOC Patients in revised 2014 International Federation of Gynecology and Obstetrics (FIGO) stage III-IV who underwent PDS between 2017 and 2019 from Yunnan Cancer Hospital were included. Clinical data including the levels of preoperative serum HE4, CA125, CA153 and mid-lower abdominal CT-enhanced scan results were collected. The logistics regression analysis was performed to find factors associated with sub-optimal debulking surgery (SDS). The receiver operating characteristic curve was used to evaluate the predictive performances of selected variables in the outcome of primary debulking surgery. The predictive index value (PIV) model was constructed to predict the outcome of SDS. Results Optimal surgical cytoreduction was achieved in 61.84% (47/76) patients. The value for CA125, HE4, CA153, ROMA index and Suidan score was lower in optimal debulking surgery (ODS) group than SDS group. Based on the Youden index, which is widely used for evaluating the performance of predictive models, the best cutoff point for the preoperative serum HE4, CA125, CA153, ROMA index and Suidan score to distinguish SDS were 431.55 pmol/l, 2277 KU/L, 57.19 KU/L, 97.525% and 2.5, respectively. Patients with PIV≥5 may not be able to achieve optimal surgical cytoreduction. The diagnostic accuracy, NPV, PPV and specificity for diagnosing SDS were 73.7%, 82.9%, 62.9% and 72.3%, respectively. In the constructed model, the AUC of the SDS prediction was 0.770 (95% confidence interval: 0.654-0.887), P&lt;0.001. Conclusion Preoperative serum CA153 level is an important non-invasive predictor of primary SDS in advanced AOC, which has not been reported before. The constructed PIV model based on Suidan's predictive model plus HE4, CA125, CA153 and ROMA index can noninvasively predict SDS in AOC patients, the accuracy of this prediction model still needs to be validated in future studies.

Laparoscopic versus laparotomic surgical treatment in apparent stage I ovarian cancer: a multi-center retrospective cohort study

Abstract Background Laparoscopic treatment shows non-inferior survival outcomes and better surgical outcomes in apparent stage I ovarian cancer (OC) in some studies but has not been well defined. Methods We conducted a retrospective study of patients with apparent stage I OC treated in two hospitals between 2012 and 2022. The surgical and oncologic outcomes were evaluated between patients receiving laparoscopic and laparotomic surgery. Results We identified 37 patients with apparent stage I OC, including 15 (40.5%) serous carcinomas, 9 (24.3%) mucinous cancers, 3 (8.1%) endometroid cancers, 2 clear cell carcinomas, and 8 (21.6%) non-epithelial cancers. Sixteen patients received laparoscopic surgery and the other 21 patients underwent laparotomic surgery. The median age (44.5 vs. 49.0 years), mean mass size (10.5 vs. 11.3 cm), and median follow-up time (43.5 vs. 75.0 months) showed no statistically significant differences between patients in laparoscopic and laparotomic groups (all P &gt; 0.05). All the patients underwent comprehensive surgical staging surgery, and the mean surgical time (213.5 vs. 203.3 min, P = 0.507), number of lymph nodes sampling (18.6 vs. 17.5, P = 0.359), proportion of upstaging (12.5% vs. 19.0%, P = 0.680), and postoperative complications (no Accordion Severity Grading System grade ≥ 3) were comparable between two surgical groups. Moreover, patients in the laparoscopic group had significantly less intraoperative blood loss (231.3 vs. 352.4 mL, P = 0.018), shorter interval between surgery and postoperative adjuvant chemotherapy (7.4 vs. 9.5 days, P = 0.004), shorter length of hospital stay (9.9 vs. 13.8 days, P &lt; 0.001) than those treated with laparotomic surgery. During a median follow-up of 54.0 months, 9 (24.3%) relapsed and 1 (2.7%) died, with a 5-year recurrence-free survival (RFS) and disease-specific survival (DSS) rate of 70.6% and 100%, respectively. However, the 5-year RFS (93.3% vs. 58.8%, P = 0.084) and DSS (100% vs. 100%, P = 0.637) rates did not significantly differ between the two groups. Conclusion Laparoscopic surgical treatment had less intraoperative blood loss, earlier postoperative adjuvant chemotherapy administration, shorter hospitalization time, and non-inferior survival outcomes in apparent stage I OC when compared with laparotomic surgery.

CD47—a novel prognostic predicator in epithelial ovarian cancer and correlations with clinicopathological and gene mutation features

Abstract Background Epithelial ovarian cancer (EOC) is insensitive to immunotherapy due to its poor immunogenicity; thus, suitable biomarkers need to be identified for better prognostic stratification and individualized treatment. CD47 is a novel immunotherapy target; however, its impact on EOC prognosis is controversial and correlation with genetic features is unclear. The aim of this study was to investigate the prognostic significance of CD47 and its correlations with biological behaviors and genetic features of EOC. Methods Immunohistochemistry (IHC) and next-generation sequencing (NGS) were performed to examine expressions of CD47, PD-L1, and genomic mutations in the tissue samples of 75 EOC patients. Various clinicopathologic and genomic features were then evaluated to determine their correlation with CD47 expression. Kaplan–Meier analysis and Cox regression analysis were used to identify independent prognostic factors. Risk score modeling was then established, and the predictive capacity of this model was further confirmed by nomogram analysis. Results CD47 was mainly expressed in the tumor cell membrane and cytoplasm, and the rate of high CD47 expression was 63.7%. CD47 expression was associated with various clinicopathological factors, including FIGO stage, CA125 and HE4 value, presence of multidisciplinary surgeries, presence and volume of ascites, lymph-node metastasis, Ki-67 index and platinum-resistant, as well as genetic characteristics like BRCA mutation, HRD status, and TP53 mutation in EOC. Patients with high CD47 expression showed worse prognosis than the low-expression group. Cox regression analysis demonstrated that CA125, CD47, and BRCA mutation were independent factors for EOC prognosis. Patients were then categorized into high-risk and low-risk subgroups based on the risk score of the aforementioned independent factors, and the prognosis of the high-risk group was worse than those of the low-risk group. The nomogram showed adequate discrimination with a concordance index of 0.777 (95% CI, 0.732–0.822). The calibration curve showed good consistency. Conclusion CD47 correlated with various malignant biology and genetic characteristics of EOC and may play pivotal and multifaceted roles in the tumor microenvironment of EOC Finally, we constructed a reliable prediction model centered on CD47 and integrated CA125 and BRCA to better guide high-risk population management.

The management of uterine tumor resembling an ovarian sex cord tumor (UTROSCT): case series and literature review

Abstract Aims To present a case series of 11 rare uterine tumors resembling ovarian sex cord tumors (UTROSCTs), and review the literature on this topic to offer up-to-date treatment management for UTROSCTs. Method Eight cases from Fujian Cancer Hospital between January 2017 and May 2023 and three patients from Fujian Union Hospital between October 2012 and October 2020 were retrospectively reviewed. All cases were pathologically confirmed as UTROSCTs by two senior and experienced pathologists. Clinical behaviors, medical data, histopathological features, therapy approaches, and survival outcomes were discussed. Results The median age at initial diagnosis was 53 years (29–70 years). 3 (27.3%) patients were under 40. Seven cases presented with abnormal vaginal bleeding, one with menstrual disorder, one with abnormal vaginal secretion, and two patients were accidentally found by physical examination without any symptoms. Three patients were initially misdiagnosed with endometrial cancer by MRI. Curettage was performed in all cases. Nine of them were well diagnosed by routine curettage, except for two samples, which were identified after surgery. Immunohistochemical biomarkers, such as CD99, Desmin, WT-1, CK, Vimentin, SMA, α-Inhibin, Ki67, CD56, ER, PR, and CR, tend to be positive in UTRO SCs patients. Six patients underwent hysterectomy with bilateral salpingo-oophorectomy. Two cases received a radical hysterectomy with bilateral salpingo-oophorectomy, retroperitoneal lymph node dissection, and omentum dissection. Three UTROSCTs were under observation after mass resection. The median PFS was 24 months (range 1–125 months). Conclusion UTROSCT is a rare mesenchymal tumor with low malignant potential. Treatment modalities should be carefully considered to balance the therapy outcomes and patient needs. Surgery conservative management might be suitable for young women with fertility desires.

The impact of lymphadenectomy on ovarian clear cell carcinoma: a systematic review and meta-analysis

Abstract Background Ovarian clear cell carcinoma (OCCC) shares treatment strategies with epithelial ovarian cancer (EOC). Due to OCCC's rarity, there's a lack of prospective studies on its surgery, resulting in heterogeneous and limited existing data. This study aims to clarify the prognostic significance of lymphadenectomy in OCCC patients. Methods We systematically searched Web of Science, Scopus, PubMed, and Google Scholar until July 2023 for studies investigating lymphadenectomy's effects on OCCC patients. We calculated pooled hazard ratios (HR) with 95% confidence intervals (CI). This study is registered in PROSPERO (CRD42021270460). Results Among 444 screened articles, seven studies (2883 women) met inclusion criteria. Our analysis revealed that lymphadenectomy significantly improved disease-specific survival (DSS) (HR = 0.76, 95%CI = 0.60–0.95, P = 0.02) and disease-free survival (DFS) (HR = 0.58, 95%CI = 0.34–0.99, P = 0.05). However, it did not significantly affect overall survival (OS) (HR = 0.80, 95%CI = 0.60–1.06, P = 0.12) or progression-free survival (PFS) (HR = 0.95, 95%CI = 0.64–1.42, P = 0.79). Notably, some earlier studies reported no survival benefit, warranting cautious interpretation. Conclusion Lymphadenectomy does not significantly enhance OS and PFS for OCCC but does improve DFS and DSS. Tailoring treatment to individual patient profiles is imperative for optimal outcomes. Precise preoperative or intraoperative lymph node metastasis detection is essential for identifying candidates benefiting from lymphadenectomy. Collaborative international efforts and an OCCC database are pivotal for refining future treatment strategies.

Cytoreductive surgery is feasible in patients with limited regional platinum-resistant recurrent ovarian cancer

Abstract Introduction To evaluate the efficacy of cytoreductive surgery versus chemotherapy for the treatment of limited regional, platinum-resistant ovarian cancer (PROC). Materials and methods The clinical records of all patients with PROC treated in our center between March 2015 and March 2022 were retrospectively reviewed. We compared the oncology outcomes of patients who received cytoreduction or chemotherapy alone at relapse and presented information about postoperative adjuvant chemotherapy. Results Among 52 patients with limited regional recurrence, 40.4% (21/52) underwent cytoreduction because of platinum resistance, and 59.6% (31/52) received chemotherapy alone. No residual disease (R0) was achieved in 20 patients (95.2%). The severe morbidity rate within 30 days after the surgery was 15%. The median follow-up was 70.6 months. Compared with the chemotherapy alone group, the surgery group with R0 had better progression-free survival (PFS) (10.6 vs. 5.1 months; hazard ratio (HR) = 0.421; P = 0.0035) and post-relapse survival (PRS) (32.6 vs. 16.3 months; HR = 0.478; P = 0.047), but there was no difference in overall survival (OS) between the two groups. Laparoscopy is associated with lesser intraoperative blood loss with no differences in survival and postoperative complications compared to the open approach (P = 0.0042). Subgroup survival analysis showed that compared with chemotherapy alone, surgery prolonged PFS in patients regardless of tumor size (greater than or equal to 4 cm or less). Surgery group patients who achieved R0 had an objective response rate (ORR) of 36.8% (7/19), among whom 40% (4/10) received platinum rechallenge chemotherapy and 33.3% (3/9) were administered non-platinum chemotherapy. Conclusion When well-selected PROC patients with limited regional recurrence achieved R0, their outcomes were superior to those of patients who received only chemotherapy with an acceptable morbidity rate. Laparoscope technology could be a reliable alternative surgical approach. The reintroduction of platinum agents may be considered following surgery. Further analyses in a larger population are warranted to elucidate the risks and benefits of this surgery and adjuvant chemotherapy strategy.

Fertility-sparing re-treatment for endometrial cancer and atypical endometrial hyperplasia patients with progestin-resistance: a retrospective analysis of 61 cases

Abstract Objective This study aimed to evaluate the oncological and reproductive outcomes of fertility-preserving re-treatment in progestin-resistant endometrial carcinoma (EC) and atypical endometrial hyperplasia (AEH) women who desire to maintain their fertility. Methods Our study included 61 progestin-resistant EC/AEH patients. These patients underwent treatment with gonadotropin-releasing hormone agonist (GnRHa) solely or a combination of GnRHa with levonorgestrel-releasing intrauterine system (LNG-IUD) or aromatase inhibitor (AI). Histological evaluations were performed every 3–4 months. Upon achieving complete remission (CR), we recommended maintenance treatments including LNG-IUD, cyclical oral contraceptives, or low-dose cyclic progestin until they began attempting conception. Regular follow-up was conducted for all patients. The chi-square method was utilized to compare oncological and fertility outcomes, while the Cox proportional hazards regression analysis helped identify risk factors for CR, recurrence, and pregnancy. Results Overall, 55 (90.2%) patients achieved CR, including 90.9% of AEH patients and 89.7% of EC patients. The median re-treatment time was 6 months (ranging from 3 to 12 months). The CR rate for GnRHa alone, GnRHa + LNG-IUD and GnRHa + AI were 80.0%, 91.7% and 93.3%, respectively. After a median follow-up period of 36 months (ranging from 3 to 96 months), 19 women (34.5%) experienced recurrence, 40.0% in AEH and 31.4% in EC patients, with the median recurrence time of 23 months (ranging from 6 to 77 months). Among the patients who achieved CR, 39 expressed a desire to conceive, 20 (51.3%) became pregnant, 11 (28.2%) had successfully deliveries, 1 (5.1%) was still pregnant, while 8 (20.5%) suffered miscarriages. Conclusion GnRHa-based fertility-sparing treatment exhibited promising oncological and reproductive outcomes for progestin-resistant patients. Future larger multi-institutional studies are necessary to confirm these findings.

Role of fallopian tube and cervical canal occlusion in preventing intra-operative tumour spillage in early endometrial cancer- a pilot study

Recent studies have found the presence of post- hysterectomy atypical glandular cells in upper vagina in ~ 30% patients of Endometrial Cancer (EC) with implications of causing isolated vaginal recurrence. The primary objective was to determine the effectiveness of cervical canal and fallopian tube occlusion in preventing intra-operative tumour spillage in EC. A Prospective Interventional Single Institutional pilot study with random allocation to two arms using computer- generated random number sequence was conducted between January 2022 to Feb 2023. Patients with histologically confirmed epithelial endometrial cancer, including endometrioid carcinoma, papillary serous, clear-cell, squamous, mucinous, undifferentiated, and carcino-sarcoma with surgery as primary definitive treatment modality were included. Spillage was detected using vaginal smear and peritoneal wash cytology taken pre- and post- hysterectomy. In interventional arm, cervical os and fallopian tube were occluded using silk sutures as additional steps during surgery. Rate of negative to positive conversion of vaginal smear and peritoneal wash cytology obtained before and after hysterectomy in the interventional arm was compared with control arm who underwent surgery with standard surgical steps. Out of 33 eligibile patients, 3 were excluded due to double primaries and history of radiation pelvis. The two arms of 15 patients each were comparable with respect to clinico-pathological characteristics. The most common histology, grade, degree of myometrial invasion, LVSI, stage, and mean tumour diameter was endometrioid variety (100%), low-grade (83.3%), & >1/2 (50%), negative (83.3%), 1 A (41.7%), and 4 cm in interventional arm and endometrioid (100%), low grade (76.9%), >1/2 (84.6%), negative (92.3%), 1B (84.6%), and 4.5 cm in non- interventional arm respectively. None of the patient in either arm had negative to positive conversion of vaginal and/or peritoneal cytology. We observed no difference of cervical and tubal occlusion on tumour cell spillage in EC. CTRI/2022/05/042348.

Comparison of clinical characteristics and prognosis in endometrial carcinoma with different pathological types: a retrospective population-based study

Abstract Background Endometrial carcinoma (EC) is the second most common gynecological malignancy, and the differences between different pathological types are not entirely clear. Here, we retrospectively collected eligible EC patients to explore their differences regarding clinical characteristics and prognosis. Methods Five hundred seventy EC patients from the First Affiliated Hospital of Zhengzhou University were included. Prognostic factors were measured using the univariate/multivariate Cox models. Overall survival (OS) and progression-free survival (PFS) were the primary and secondary endpoints, respectively. Results In total, 396 patients with uterine endometrioid carcinoma (UEC), 106 patients with uterine serous carcinoma (USC), 34 patients with uterine mixed carcinoma (UMC), and 34 patients with uterine clear cell carcinoma (UCCC) were included. Comparison of baseline characteristics revealed patients diagnosed with UEC were younger, had more early clinical stage, and had lower incidence of menopause and lymph node metastasis. Compared to UEC, other pathological EC obtained more unfavorable OS (UCCC: HR = 12.944, 95%CI = 4.231–39.599, P &lt; 0.001; USC: HR = 5.958, 95%CI = 2.404–14.765, P &lt; 0.001; UMC: HR = 1.777, 95%CI = 0.209–15.114, P = 0.599) and PFS (UCCC: HR = 8.696, 95%CI = 1.972–38.354, P = 0.004; USC: HR = 4.131, 95%CI = 1.243–13.729, P = 0.021; UMC: HR = 5.356, 95%CI = 0.935–30.692, P = 0.060). Compared with UEC patients, the OS of UCCC patients in stage I–II and USC patients in stage III–IV were significantly worse, while UMC patients in stage I–II favored poorer PFS. The OS of UCCC patients receiving no postoperative adjuvant therapy or chemotherapy alone were significantly worse. Conclusions The baseline characteristics of UEC and other rare EC types varied greatly, and the prognostic significance of different pathological types on EC patients depended on clinical tumor stages and therapeutic options.

Undifferentiated uterine sarcoma : experience of a single center

To investigate the clinicopathological characteristics and prognosis of patients with undifferentiated uterine sarcomas (UUS). 29 patients with UUS who were treated at our institution between 2001 and 2020 were analyzed. The median age at diagnosis was 52 years (range: 26-70 years). The FIGO 2009 distribution by stage was as follows: stage I, 17 patients (58.6%); stage II, 5 patients (17.2%); stage III, 4 patients (13.8%); and stage IV, 3 patients (10.3%). For 28 patients who underwent surgical treatment, 27 patients (96.4%) underwent total/sub-radical/radical hysterectomy combined bilateral salpingo-oophorectomy, 17 (58.6%) pelvic lymphadenectomy, 7 (24.1%) para-aortic lymphadenectomy and 8 (28.6%) patients underwent omentectomy, as part of the initial surgical treatment. The median follow-up was 23.4 months (range: 4.5-200.2 months). 18 patients (62.1%) died during follow up, and 13 patients (72.2%, 13/18) died within 2 years after diagnosis. Median progression-free survival (mPFS) and overall survival (mOS) for the entire cohort were 15.5 and 27.4 months, respectively. 2-year and 5-year PFS were 40.3% and 26.9%. 2-year and 5-year OS were 54.0% and 36.5%. Stage-specific median PFS and OS were as follows: stage I-II-17.7 and 35.5 months, stage III-IV-6.0 and 6.7 months. Patients with recurrent UUS who underwent cytoreduction surgery associated with an improved overall survival (mOS: 52.9 vs. 17.9 months), but the difference was not statistically significant (P = 0.081). UUS are a rare group of tumors with an aggressive behavior and poor outcomes. A majority rapidly develops distant metastases despite surgical resection.

Association of CYP7B1 expression with the prognosis of endometrial cancer: a retrospective study

Endometrial cancer (EC) tissues express CYP7B1, but its association with prognosis needs to be investigated. Immunohistochemistry and image analysis software were used to assess CYP7B1 protein expression in paraffin-embedded endometrial tumor sections. Associations between CYP7B1 and clinical factors were tested with the Wilcoxon rank-sum test. Kaplan-Meier curves were employed to describe survival, and differences were assessed using the log-rank test. Cox regression analysis was used to assess the association between CYP7B1 expression and the prognosis of patients with EC. A total of 307 patients were enrolled with an average age of 52.6 ± 8.0 years at diagnosis. During the period of follow-up, 46 patients (15.0%) died, and 29 (9.4%) suffered recurrence. The expression of CYP7B1 protein is significantly higher in the cytoplasm than in the nucleus (P < 0.001). Patients aged < 55 years (P = 0.040), ER-positive patients (P = 0.028) and PR-positive patients (P < 0.001) report higher levels of CYP7B1 protein. Both univariate (HR = 0.41, 95% CI: 0.18-0.90, P = 0.025) and multivariate (HR = 0.35, 95%CI:0.16-0.79, P = 0.011) Cox regression analyses demonstrate that high CYP7B1 protein expression predicts longer overall survival (OS). When considering only ER-positive patients (n = 265), CYP7B1 protein expression is more strongly associated with OS (HR = 0.20,95%CI:0.08-0.52, P = 0.001). The 3-year OS and 5-year OS in the low-CYP7B1 subgroup are 81.6% and 76.8%, respectively; while in the high-CYP7B1 subgroup are 93.0% and 92.0%, respectively (P = 0.021). High CYP7B1 protein expression predicted longer OS, suggesting that it may serve as an important molecular marker for EC prognosis.

RETRACTED ARTICLE: LncRNA SOX21-AS1 accelerates endometrial carcinoma progression through the miR-7-5p/RAF1 pathway

Abstract Background Endometrial carcinoma (EC) is one of the world’s typical female reproductive tract malignancies, mostly occurring in postmenopausal women. Many reports have confirmed that long non-coding RNA SOX21 antisense RNA1 (lncRNA SOX21-AS1) is associated with the progressions of various cancer. However, the mechanism of SOX21-AS1 in EC remains unclear. Our study is intended to probe the mechanisms of SOX21-AS1 on EC progression. Methods The CCK-8 assay and colony formation detected cell proliferation. Cell migration and invasion were assessed by transwell analysis. Apoptosis was measured by flow cytometry assay. Bioinformatics software predicted target binding and confirmed using a luciferase reporter analysis. Results SOX21-AS1 expression was upregulated in EC tumor tissues and cells. High expression of SOX21-AS1 was associated with poor overall survival. Silencing of SOX21-AS1 restrained cell proliferation, migration, invasion, and increased apoptosis in HEC-1A and Ishikawa cells. Additionally, bioinformatics analysis demonstrated that SOX21-AS1 modulated RAF1 expression by competitively binding to miR-7-5p. Functionally, silencing of RAF1 reversed the functions of miR-7-5p inhibitor in the proliferation, invasion, and apoptosis of HEC-1A/sh-SOX21-AS1 and Ishikawa/sh-SOX21-AS1 cells. Conclusions SOX21-AS1 promoted the pathological development of EC by regulating the miR-7-5p/RAF1 pathway. This research may provide a novel target for EC therapy.

Survival outcomes and the prognostic significance of clinicopathological features in patients with endometrial clear cell carcinoma: a 35-year single-center retrospective study

AbstractBackgroundTo evaluate the oncological outcomes and the impact of clinicopathological factors on endometrial clear cell carcinoma (ECCC) outcomes.MethodsMedical records of patients with primary ECCC treated at our center between 1985 and December 2020 were reviewed. Overall survival (OS) and progression-free survival (PFS) were the endpoints. The Kaplan–Meier method and Cox regression analysis were used.ResultsIn total, 156 patients were included, of whom 59% and 41% had early- and advanced-stage ECCC, respectively. The median age of onset was 61 years, and 80.8% of the patients were postmenopausal. Ninety-two (59%) and 64 (41%) patients had pure ECCC and mixed endometrial carcinoma with clear cell carcinoma (CCC) components, respectively. Mixed pathological components, elevated cancer antigen 125 levels, positive lymphovascular space invasion, deep myometrial invasion, and malignant peritoneal washing cytology (PWC) were more frequently observed in the advanced stage. Thirty-nine patients (25%) experienced relapse and 32 patients (20.5%) died. The 5-year PFS and OS rates for the entire cohort were 72.6% and 79%, respectively. Multivariate analysis showed that advanced-stage disease and positive PWC significantly decreased PFS, while advanced-stage disease and older age (&gt; 61 years) significantly decreased OS.ConclusionsECCC is a rare and aggressive type II endometrial carcinoma that is common in older women and patients with advanced-stage disease. Positive PWC was associated with decreased PFS, although its presence did not influence the stage. Positive PWC, and advanced stage and older age were independent negative prognostic factors.

Characteristics of systematic lymph node dissection and influencing factors of sentinel lymph node biopsy using carbon nanoparticles in endometrial carcinoma: a single-center study

Abstract Background Carbon nanoparticles (CNPs) are a new tracer for lymph node mapping, which can quickly reach and develop lymph nodes through a lymphatic network. This research investigated the characteristics of systematic lymph node dissection and sentinel lymph node biopsy mapped with CNPs in endometrial carcinoma. Methods We first applied CNPs to systematic lymph node dissection in 18 endometrial carcinoma patients as the study group and another 18 endometrial carcinoma patients who were not injected with anything served as the control group. Then, we applied CNPs to sentinel lymph nodes biopsy in 54 endometrial carcinoma patients. All 54 patients received systematic lymph node dissection after sentinel lymph node biopsy. The detection rate, sensitivity, specificity, and accuracy of systematic lymph node dissection and sentinel lymph node biopsy by CNPs were respectively analyzed. A nomogram model for predicting the success of sentinel lymph node mapping was established. Results The average number of lymph nodes removed in the CNP-labeled study group was higher than that in the control group (p&lt;0.001). CNPs improved the number of lymph nodes with a diameter ≤ 0.5cm. The detection rate, sensitivity, specificity, and accuracy of sentinel lymph nodes biopsy by CNPs for endometrial carcinoma were 70.4%, 100%, 100%, and 100%, respectively. The nomogram model included factors of long menopause time, cervical cyst, and hard cervical texture, and the area of ROC curve was 0.816. Conclusions CNPs improve the detection rate of small lymph nodes. CNPs can trace sentinel lymph nodes in evaluating lymph node metastasis in endometrial carcinoma.

Expression of EMT-related genes in lymph node metastasis in endometrial cancer: a TCGA-based study

Abstract Background Endometrial cancer (EC) with metastasis in pelvic/para-aortic lymph nodes suggests an unsatisfactory prognosis. Nevertheless, there is still rare literature focusing on the role of epithelial-mesenchymal transition (EMT) in lymph node metastasis (LNM) in EC. Methods Transcriptional data were derived from the TCGA database. Patients with stage IA–IIIC2 EC were included, constituting the LN-positive and LN-negative groups. To evaluate the extent of EMT, an EMT signature composed of 315 genes was adopted. The EMT-related genes (ERGs) were obtained from the dbEMT2 database, and the differentially expressed ERGs (DEERGs) between these two groups were screened. On the basis of DEERGs, pathway analysis was carried out. We eventually adopted the logistic regression model to build an ERG-based gene signature with predictive value for LNM in EC. Results A total of 498 patients were included, with 75 in the LN-positive group. Median EMT score of tumor tissues from LN-negative group was − 0.369, while that from the LN-positive group was − 0.296 ( P  &lt; 0.001), which clearly exhibited a more mesenchymal phenotype for LNM cases on the EMT continuum. By comparing expression profiles, 266 genes were identified as DEERGs, in which 184 were upregulated and 82 were downregulated. In pathway analysis, various EMT-related pathways were enriched. DEERGs shared between molecular subtypes were comparatively few. The ROC curve and logistic regression analysis screened 7 genes with the best performance to distinguish between the LN-positive and LN-negative group, i.e., CIRBP , DDR1 , F2RL2 , HOXA10 , PPARGC1A , SEMA3E , and TGFB1 . A logistic regression model including the 7-gene-based risk score, age, grade, myometrial invasion, and histological subtype was built, with an AUC of 0.850 and a favorite calibration ( P  = 0.074). In the validation dataset composed of 83 EC patients, the model exhibited a satisfactory predictive value and was well-calibrated ( P  = 0.42). Conclusion The EMT status and expression of ERGs varied in LNM and non-LNM EC tissues, involving multiple EMT-related signaling pathways. Aside from that, the distribution of DEERGs differed among molecular subtypes. An ERG-based gene signature including 7 DEERGs exhibited a desirable predictive value for LNM in EC, which required further validation based upon clinical specimens in the future.

SLERT, as a novel biomarker, orchestrates endometrial cancer metastasis via regulation of BDNF/TRKB signaling

AbstractBackgroundRecent evidence suggests that the box H/ACA small nucleolar RNA (snoRNA)-ended long noncoding RNA (lncRNA), SLERT, plays a critical role in gene regulation. However, its role in cancer remains undetermined. Herein, we explored its implication in human endometrial cancer (EC).MethodsEC plasma and tissue samples were collected for the detection of SLERT expression using qRT-PCR method. The functional investigation was tested by CCK-8 and transwell assays. Luciferase reporter, RNA pull-down, and immunoprecipitation (RIP) assays were used to determine the regulatory network involved in SLERT. The in vivo effect of SLERT was tested by caudal vein lung metastasis model.ResultsStable knockdown of SLERT significantly inhibited EC cell (KLE and AN3CA) migration and invasion, while it did not affect cell viability. SLERT induced epithelial-mesenchymal transition (EMT) via elevating N-cadherin and Vimentin and downregulating E-cadherin. Further investigation showed that SLERT directly binds to METTL3, increasing the m6A levels of BDNF mRNA; then, the m6A sites were read by IGF2BP1, enhancing BDNF mRNA stability, followed by the activation of BDNF/TRKB signaling, an inducer of EMT. The animal model showed that overexpression of SLERT increased EC cell lung metastasis, and this effect was effectively blocked by BDNF silencing or treatment with TRKB inhibitor k252a. Clinically, EC patients have high levels of SLERT both in tissue or plasma, which might be used as a biomarker of diagnosis and prognosis.ConclusionOur findings, for the first time, uncover the metastasis-promoting effect of SLERT in EC via in vitro and in vivo evidence, providing a potential therapeutic target for metastatic EC treatment.

TIMM8A is associated with dysfunction of immune cell in BRCA and UCEC for predicting anti-PD-L1 therapy efficacy

Abstract Background TIMM8A is a protein-coding gene located on the X chromosome. There is evidence that TIMM8A plays an important role in mitochondrial morphology and fission. Studies have shown that mitophagy and fission could affect the function of immune cells. However, there is currently no research on this gene’s role in cancer occurrence and progression. Methods TIMM8A expression was analyzed via the Tumor Immune Estimation Resource (TIMER) site and UALCAN database. We evaluated the influence of TIMM8A on clinical prognosis using Kaplan-Meier plotter, the PrognoScan database, and Human Protein Atlas (HPA). The correlations between TIMM8A and cancer immune infiltrates were investigated via TIMER. Tumor Immune Dysfunction and Exclusion (TIDE) was used to evaluate the potential of tumor immune evasion. Functions of TIMM8A mutations and 50 genes significantly associated with TIMM8A mutations in breast cancer (BRCA) and uterine corpus endometrial cancer (UCEC) were analyzed by GO and KEGG in LinkedOmics database. Results We investigated the role of TIMM8A in multiple cancers and found that it was significantly associated with poor prognosis in BRCA and UCEC. After analyzing the effect of TIMM8A on immune infiltration, we found Th2 CD4+ T cells might be a common pathway by which TIMM8A contributed to poor prognosis in BRCA and UCEC. Our results suggested that myeloid-derived suppressor cells (MDSC) and tumor-associated M2 macrophages (TAM M2) might be important factors in immune evasion through T cell rejection in both cancers, and considered TIMM8A as a biomarker to predict the efficacy of this therapy in BRCA and UCEC. The results of TIMM8A enrichment analysis showed us that abnormally expressed TIMM8A might affect the mitochondrial protein in BRCA and UCEC. Conclusions Contributed to illustrating the value of TIMM8A as a prognostic biomarker, our findings suggested that TIMM8A was correlated with prognosis and immune infiltration, including CD8+ T cells, Th2 CD4+ T cells, and macrophages in BRCA and UCEC. In addition, TIMM8A might affect immune infiltration and prognosis in BRCA and UCEC by affecting mitophagy. We believed it could also be a biomarker to predict the efficacy of anti-PD-L1 therapy and proposed to improve the efficacy by eliminating MDSC and TAM M2.

A progressive and refractory case of breast cancer with Cowden syndrome

Abstract Background Cowden syndrome is a rare autosomal-dominant disease with a high risk of malignant tumors of the breast, commonly caused by germline mutations in the PTEN gene. Most breast cancers related to Cowden syndrome showed typically a slow-growing and favorable clinical course. Here, we report a progressive case of triple-negative breast cancer in a patient who was diagnosed with Cowden syndrome. Case presentation A 35-year-old female with breast cancer was referred to our hospital. Histopathological examination of the tumor showed that it was triple-negative breast cancer with high proliferation marker. Preoperative positron emission tomography-computed tomography showed abnormal uptake in the left cerebellar hemisphere in addition to the right breast and axillary lymph node. Brain T2-weighted magnetic resonance imaging revealed hyperintense bands in the left cerebellar hemisphere lesion, which demonstrated a “tiger-stripe” appearance. The patient’s mother had died of endometrial cancer. Subsequently, she underwent genetic testing, leading to a diagnosis of Cowden syndrome with a pathogenic variant c.823_840del.18 at exon 8 in PTEN. She was treated with neoadjuvant chemotherapy of eribulin and cyclophosphamide followed by adriamycin and cyclophosphamide. However, her tumors increased after these treatments. She was immediately surgically treated and received adjuvant chemotherapy of capecitabine. Unfortunately, the cancer recurred in the lung nine months after surgery. We then administered paclitaxel and bevacizumab therapy, but the disease rapidly progressed. Consequently, the patient died due to breast cancer about three months after recurrence. Conclusion We report an aggressive case of cancer with Cowden syndrome which was resistant to standard chemotherapy. Alteration of the phosphatidylinositol-3 kinase/Akt/mammalian target of rapamycin pathway due to inactivating PTEN protein may be associated with chemoresistance and serves as a candidate for therapeutic intervention in PTEN-related cancers.

Primary low-grade extrauterine endometrial stromal sarcoma: analysis of 10 cases with a review of the literature

Abstract Background This study aimed to analyze the clinical and pathological features of extrauterine endometrial stromal sarcoma (EESS) and explore an effective therapeutic regimen to reduce the recurrence rate in low-grade EESS patients. Methods Ten LG-EESS patients who were treated at the Chinese Academy of Medical Sciences Cancer Institute and Hospital from June 1999 to June 2019 were collected and analyzed. Results (1) Patient demographics are summarized in manuscript. Preoperative CA125 examination showed that 8 patients had a median level of 49.5 U/L (15.4–168.0 U/L). (2) All ten patients underwent tumor cytoreductive surgery. Five patients underwent optimal tumor resection and achieved an R0 resection. After the initial surgery, 7 patients who had multiple metastasis were treated with adjuvant chemotherapy, 2 patients with vaginal ESS were treated with chemotherapy and radiation therapy, and 6 patients with ER/PR positive received hormone therapy with or without chemotherapy. (2) Most EESS patients had multiple tumors. The omentum was the most commonly affected site, followed by the ovaries. (3) The median follow-up was 94 (range: 27–228) months, and recurrence was observed in 3 patients (n = 10, 30%) who underwent non-optimal surgery and no hormone therapy. The 5-year and 10-year DFS rates were both 70%, as shown in Fig. 2. OS was both 100% at 5 and 10 years. Conclusion As a conclusion, EESS is a rare disease and LG-EESS has a good prognosis. Surgery remains the available treatment for patients. LG-EESS has a risk of late recurrence which requires a long-term follow-up. With a limited sample size, our study shows optimal tumor reductive surgery and adjuvant hormone therapy may significantly reduce the risk of recurrence.

The MCM3AP-AS1/miR-126/VEGF axis regulates cancer cell invasion and migration in endometrioid carcinoma

Abstract Background Long non-coding RNA (lncRNA) MCM3AP-AS1 plays an oncogenic role in several malignancies, but its role in endometrioid carcinoma (EC) is unclear. This study was carried out to explore the role of MCM3AP-AS1 in EC. Methods A total of 60 EC patients were enrolled in this study. Expression levels of MCM3AP Antisense RNA 1 (MCM3AP-AS1), microRNA-126 (miR-126), and vascular endothelial growth factor (VEGF) in tissues and transfetced cells were measured by RT-qPCR. Cell transfections were performed to explore the interaction among MCM3AP-AS1, miR-126 and VEGF. Transwell assays were perfromed to evaluate the invasion and migration abilities of HEC-1 cells after transfection. Results MCM3AP-AS1 was upregulated in EC and predicted poor survival. MCM3AP-AS1 directly interacted with miR-126. In EC cells, overexpression of MCM3AP-AS1 and miR-126 did not significantly affect the expression of each other. In addition, overexpression of MCM3AP-AS1 increased the expression levels of VEGF, a target of miR-126. Moreover, overexpression of MCM3AP-AS1 and VEGF increased the migration and invasion rates of EC cells, while overexpression of miR-126 suppressed these cell behaviors. Overexpression of MCM3AP-AS1 attenuated the role of miR-126 in cell invasion and migration. Conclusions Therefore, MCM3AP-AS1 may serve as a competing endogenous RNA (ceRNA) of miR-126 to upregulate VEGF, thereby regulating cancer cell behaviors in EC.

Identification of six candidate genes for endometrial carcinoma by bioinformatics analysis

Abstract Background Endometrial carcinoma (EC) is the most common gynecological malignant tumors which poses a serious threat to women health. This study aimed to screen the candidate genes differentially expressed in EC by bioinformatics analysis. Methods GEO database and GEO2R online tool were applied to screen the differentially expressed genes (DEGs) of EC from the microarray datasets. Protein-protein interaction (PPI) network for the DEGs was constructed to further explore the relationships among these genes and identify hub DEGs. Gene ontology and KEGG enrichment analyses were performed to investigate the biological role of DEGs. Besides, correlation analysis, genetic alteration, expression profile, and survival analysis of these hub DEGs were also investigated to further explore the roles of these hub gene in mechanism of EC tumorigenesis. qRT-PCR analysis was also performed to verify the expression of identified hub DEGs. Results A total of 40 DEGs were screened out as the DEGs with 3 upregulated and 37 downregulated in EC. The gene ontology analysis showed that these genes were significantly enriched in cell adhesion, response to estradiol, and growth factor activity, etc. The KEGG pathway analysis showed that DEGs were enriched in focal adhesion, leukocyte transendothelial migration, PI3K-Akt signaling pathway, and ECM-receptor interaction pathway. More importantly, COL1A1, IGF1, COL5A1, CXCL12, PTEN, and SPP1 were identified as the hub genes of EC. The genetic alteration analysis showed that hub genes were mainly altered in mutation and deep deletion. Expression validation by bioinformatic analysis and qRT-PCR also proved the expression of these six hub genes were differentially expressed in EC. Additionally, significantly better overall survival and disease-free survival were observed with six hub genes altered, and survival outcome in high expression of COL1A1, IGF1, and PTEN patients was also significantly better than low expression patients. Conclusions COL1A1, IGF1, COL5A1, CXCL12, PTEN, and SPP1 involved in the pathogenesis of EC and might be candidate genes for diagnosis of EC.

What is the impact of radical hysterectomy on endometrial cancer with cervical involvement?

Abstract Background When endometrial carcinoma invades the cervical stroma, overall survival and disease-free survival decrease. However, it is still controversial whether patients in suspected stage II should be treated with radical hysterectomy. The goal of this study is to describe the role of radical hysterectomy in patients with endometrial carcinoma and cervical involvement. Methods This was a retrospective cohort study were a total of 239 patients with endometrial carcinoma with cervical involvement from Mexico City’s National Cancer Institute were divided according to the type of hysterectomy, and the outcomes were compared using statistical analysis. Results The 5-year overall survival was 75.76% for the simple hysterectomy group and 89.19% for the radical hysterectomy group, without achieving statistical significance. The 5-year disease-free survival was 72.95% for the simple hysterectomy group and 64.31% for the radical hysterectomy group, without achieving statistical significance. Radicality was associated with longer surgical times, intraoperative complications, and bleeding over 500 ml. Conclusions In patients with endometrial carcinoma with cervical involvement, radical hysterectomy does not improve prognosis or alter adjuvant therapy.

Tumor biomarkers contribute to the diagnosis and clinical management of the O-RADS MRI risk stratification system for epithelial ovarian tumors

To assess the effectiveness of tumor biomarkers in distinguishing epithelial ovarian tumors (EOTs) and guiding clinical decisions across each Ovarian-Adnexal Reporting and Data System (O-RADS) MRI risk category, the aim is to prevent unnecessary surgeries for benign lesions, avoid delays in treating malignancies, and benefit individuals requiring fertility preservation or those intolerant to over-extensive surgery. A total of 54 benign, 104 borderline, and 203 malignant EOTs (BeEOTs, BEOTs and MEOTs) were enrolled and retrospectively assigned risk scores. The role of tumor biomarkers in diagnosing and managing EOTs within each risk category was evaluated by combining receiver operating characteristic (ROC) curves with clinicopathological characteristics. A score of 3 was assigned to 66.67% of BeEOTs, 50.96% of BEOTs, and 13.80% of MEOTs, whereas cancer antigen 125 (CA125) ≥ 60.39 U/ml helped identify MEOTs with a low-risk time-intensity curve (TIC) for prompt surgical assessment. Only 3.7% of the BeEOTs were classified as O-RADS MRI 4/5, whereas 48.08% and 86.2% of the BEOTs and MEOTs were classified, respectively. Overall, EOTs with a score of 4/5 are candidates for semi-elective surgery owing to the low probability of benign lesions. For EOTs with a ROMA index less than 20.14% (premenopausal) or 29.9% (postmenopausal), minimally invasive surgery is recommended for diagnostic and therapeutic purposes. Comprehensive staging or cytoreductive surgery is recommended for the remaining patients, especially when fertility preservation is not a priority. The O-RADS MRI primarily differentiates BeEOTs with risk scores of 2/4/5 from BEOTs/MEOTs, while tumor biomarkers further enhance the diagnosis and clinical management of EOTs with scores of 3/4/5. Future studies should focus on multi-center, prospective studies with larger sample sizes to validate and refine the integration of O-RADS MRI with tumor biomarkers.

Efficacy and safety of secondary cytoreductive surgery with hyperthermic intraperitoneal chemotherapy in platinum-sensitive recurrent ovarian cancer: a systematic review and meta-analysis

This study aims to compare the efficacy and safety of secondary cytoreductive surgery (SCS) combined with hyperthermic intraperitoneal chemotherapy (HIPEC) versus SCS alone in the management of platinum-sensitive recurrent ovarian cancer (PSROC) through a systematic review and meta-analysis. A comprehensive search was performed in the PubMed, EMBASE, Web of Science, and Cochrane Library databases through December 31, 2024. Studies were eligible if they compared outcomes between individuals receiving SCS combined with HIPEC and those receiving SCS alone. The primary outcomes included progression-free survival (PFS) and overall survival (OS), measured using hazard ratios (HRs) with 95% confidence intervals (CIs). Secondary outcomes included the incidence of complications, reported as relative risks (RRs) with 95% CIs. Statistical analyses were conducted using Stata software (version 15.1). A total of seven studies comprising 1,136 patients were included. Of these, 563 patients underwent SCS combined with HIPEC, while 573 received SCS alone. The pooled analysis indicated that the addition of HIPEC to SCS was associated with a significant improvement in OS (HR = 0.76, 95% CI [0.62, 0.94], p = 0.01). However, no statistically significant improvement was observed in PFS (HR = 0.91, 95% CI [0.72, 1.15], p = 0.43). The overall incidence of grade ≥ 3 complications did not differ significantly between the two groups (RR = 1.42, 95% CI [1.00, 2.01], p = 0.05). Nonetheless, the incidence of nephrotoxicity (RR = 1.71, 95% CI [1.20, 2.43]) and anemia (RR = 1.38, 95% CI [1.18, 1.62]) was higher in the group treated with SCS and HIPEC. No significant difference was noted in the incidence of thrombocytopenia (RR = 1.41, 95% CI [0.76, 2.59]). The integration of HIPEC with SCS may improve OS among patients with PSROC without a marked increase in severe complications; however, increased risks of nephrotoxicity and anemia should be considered in clinical decision-making. Further standardization of HIPEC protocols and the implementation of large-scale randomized controlled trials are recommended to confirm these findings and establish definitive clinical guidelines.

Metastasis to para-aortic lymph nodes cephalad to the renal veins in patients with ovarian cancer

Abstract Background In patients with epithelial ovarian cancer, whether metastasis to para-aortic lymph nodes located cephalad to the renal veins (supra-renal PAN) should be classified as regional lymph node metastasis or distant metastasis remains controversial. This study was a preliminary retrospective evaluation of the pattern of supra-renal PAN metastasis in patients with epithelial ovarian cancer. Methods The subjects were 25 patients with epithelial ovarian cancer, primary peritoneal cancer, or fallopian tube cancer who underwent systematic dissection of the para-aortic nodes, including the supra-renal PAN, and pelvic lymph nodes (PLN). Patient factors, perioperative factors, the number of dissected lymph nodes, and pathological lymph node metastasis were investigated. Results Supra-renal PAN metastasis was found in 4/25 patients (16.0%). None of the 14 patients with pT1 or pT2 disease had supra-renal PAN metastasis, while 4/11 patients (36.4%) with pT3 or ypT3 disease had such metastases. None of the patients had isolated supra-renal PAN metastasis, while patients with supra-renal PAN metastasis also had multiple metastases to the infra-renal PAN and PLN. Conclusions In patients with epithelial ovarian cancer, supra-renal PAN metastases might be considered to be distant rather than regional metastases. Further studies are needed to better define the clinical significance of supra-renal PAN metastasis.

miR-338-3p targets WAPL to suppress proliferation and invasion in cervical cancer cells: experimental insights

This study aimed to elucidate the role of miR-338-3p in cervical cancer, focusing on its regulatory effect on the WAPL (wings apart-like homolog) gene and the consequent influence on the behavior of cervical carcinoma cells. Bioinformatic analysis identified a potential miR-338-3p binding site in the WAPL 3' untranslated region (3'UTR). This interaction was confirmed using a dual-luciferase reporter assay. The effects of miR-338-3p overexpression on the proliferation, apoptosis, cell cycle, and invasion of cervical cancer cells were subsequently evaluated. WAPL transcript levels were elevated in cervical cancer tissues compared with normal controls (P < 0.05). The GV369/miR-338-3p construct was successfully generated, and qRT-PCR confirmed robust upregulation of miR-338-3p expression in HeLa and CaSKi cells. Dual-luciferase assays verified that miR-338-3p directly binds to the 5'-AUGCUGG-3' sequence within the WAPL 3'UTR, leading to reduced luciferase activity (0.59 ± 0.01 vs 1.00 ± 0.01 and 1.16 ± 0.01, P < 0.001) compared with the negative control and mutant groups. Overexpression of miR-338-3p significantly decreased both mRNA and protein levels of WAPL (P < 0.05). Functionally, miR-338-3p overexpression markedly inhibited the proliferation of HeLa and CaSKi cells (P < 0.001), enhanced apoptosis (P < 0.001), induced cell cycle arrest at the S phase in HeLa and at the G1 phase in CaSKi cells (P < 0.05), and reduced cellular invasion and migration (P < 0.05). miR-338-3p directly targets WAPL to downregulate its expression, thereby suppressing the proliferative and invasive capacities of cervical cancer cells. These findings provide mechanistic insights into the post-transcriptional regulation of WAPL in cervical cancer.

Prognostic value of platelet to lymphocyte ratio in patients with cervical cancer: an updated systematic review and meta-analysis

The identification of biomarkers that reliably forecast cervical cancer (CC) outcomes is a key area of research. Several studies have explored the link between the platelet-to-lymphocyte ratio (PLR) and cervical cancer prognosis, though the results are not entirely conclusive. PubMed, Embase, Web of Science, and the Cochrane Library were used to search, with studies published up to May 30, 2024. The selection of studies followed predetermined inclusion and exclusion criteria. Overall survival (OS), progression-free survival (PFS), and disease-free survival (DFS) were primary outcomes. Hazard ratios (HR) and 95% confidence intervals (CIs) were calculated. Sensitivity and subgroup analyses were performed to evaluate the stability and investigate potential heterogeneity. Review Manager version 5.4.1 and STATA version 15.0 were conducted to analyze. Thirty cohort studies, involving 8,597 patients, were included. The pooled data showed that a higher PLR was associated with worse OS significantly (HR = 1.77, 95% CI: 1.43-2.19; p < 0.0001), PFS (HR = 1.69, 95% CI: 1.26-2.27; p = 0.0004), and DFS (HR = 1.57, 95% CI: 1.12-2.18; p = 0.008). Subgroup analysis indicated that the prognostic relevance of PLR was most prominent in patients who underwent both surgery and radiotherapy, as well as those from Asia and the America. Furthermore, a PLR threshold above 150 was associated with improved predictive accuracy. Increased PLR among cervical cancer patients was significantly correlated with reduced OS, PFS, and DFS, pointing to its potential role as an independent prognostic marker. Nonetheless, additional prospective research is required to verify this finding.

Development and validation of a nomogram for predicting venous thromboembolism risk in post-surgery patients with cervical cancer

Postoperative venous thromboembolism (VTE) is a potentially life-threatening complication. This study aimed to develop a predictive model to identify independent risk factors and estimate the likelihood of VTE in patients undergoing surgery for cervical cancer. We conducted a retrospective cohort study involving 1,174 patients who underwent surgery for cervical carcinoma between 2019 and 2022. The cohort was randomly divided into training and validation sets at 7:3. Univariate and multivariate logistic regression analyses were used to determine the independent factors associated with VTE. The results of the multivariate logistic regression were used to construct a nomogram. The nomogram's performance was assessed via the concordance index (C-index) and calibration curve. Additionally, its clinical utility was assessed through decision curve analysis (DCA). The predictive nomogram model included factors such as age, pathology type, FIGO stage, history of chemotherapy, the neutrophil-lymphocyte ratio (NLR), fibrinogen degradation products (FDP), and D-dimer levels. The model demonstrated robust discriminative power, achieving a C-index of 0.854 (95% CI: 0.799-0.909) in the training cohort and 0.757 (95% CI: 0.657-0.857) in the validation cohort. Furthermore, the nomogram showed excellent calibration and clinical utility, as evidenced by the calibration curve and decision curve analysis (DCA) results. We developed a high-performance nomogram that accurately predicts the risk of VTE in cervical cancer patients undergoing surgery, providing valuable guidance for thromboprophylaxis decision-making.

Meta-analysis of the diagnostic value of SOX1 methylation in different types of cervical cancer

This meta-analysis evaluates the diagnostic value of SOX1 methylation across different cervical cancer types, including squamous cell carcinoma and adenocarcinoma, to assess its efficacy as a biomarker. We reviewed studies published up to March 2024, employing a PICOS-based search strategy in databases like PubMed and Web of Science. We included clinical studies providing diagnostic performance indicators while excluding non-clinical and small-sample studies. Meta-Disc1.4 and Stata15.1 were used for statistical analyses focusing on SOX1 methylation's sensitivity, specificity, and diagnostic odds ratio. Twelve articles encompassing 18 studies with 3,213 subjects were analyzed. The overall DOR for SOX1 methylation in cervical cancer diagnosis was 68.95 (95%CI: 27.63-172.07), with a Summary Receiver Operating Characteristic AUC of 0.92, indicating high diagnostic accuracy. Specifically, the DOR for adenocarcinoma was 87.57 (95%CI: 7.05-1087.44) with an AUC of 0.89, and for squamous cell carcinoma, it was 245.87 (95% CI: 26.49-2282.40) with an AUC of 0.93, reflecting significant diagnostic potential for both cancer types. No substantial publication bias was detected (P > 0.10). SOX1 gene methylation demonstrates significant diagnostic value for both adenocarcinoma and squamous cell carcinoma of the cervix, particularly effective in large sample sizes and cervical exfoliated cell samples for early detection and screening, supporting its utility as a reliable biomarker.

Peritoneal cytology predicting distant metastasis in uterine carcinosarcoma: machine learning model development and validation

This study develops and validates a machine learning model using peritoneal cytology to predict distant metastasis in uterine carcinosarcoma, aiding clinical decision-making. This study utilized detailed clinical data and peritoneal cytology findings from uterine carcinosarcoma patients in the SEER database. Eight machine learning algorithms-Logistic Regression, SVM, GBM, Neural Network, RandomForest, KNN, AdaBoost, and LightGBM-were applied to predict distant metastasis. Model performance was assessed using AUC, calibration curves, DCA, confusion matrices, sensitivity, and specificity. The Logistic Regression model was visualized with a nomogram, and its results were analyzed. SHAP values were used to interpret the best-performing machine learning model. Peritoneal cytology, T stage, age, and tumor size were key factors influencing distant metastasis in uterine carcinosarcoma patients. Peritoneal cytology had significant weight in the prediction models. The logistic regression model demonstrated excellent predictive performance with an AUC of 0.882 in the training set and 0.881 in the internal test set. The model was visualized and interpreted using a nomogram. In comprehensive evaluations, GBM was identified as the best-performing model and was explained using SHAP values. Additionally, calibration and DCA curves indicated that both models have significant potential clinical utility. This study introduces the first effective tool for predicting distant metastasis in uterine carcinosarcoma patients by integrating peritoneal cytology features into model construction. It aids in early identification of high-risk patients, enhancing follow-up and monitoring during tumor development, and supports the optimization of personalized treatment strategies.

Para-aortic and pelvic lymphadenectomy in locally advanced cervical cancer with pelvic lymph node metastasis

This study sought to explore the efficiency of para-aortic and pelvic lymphadenectomy in the treatment of locally advanced cervical cancer (LACC) with pelvic lymph node (PLN) metastasis. A total of 171 LACC patients with imaging-confirmed pelvic lymph node metastasis were included in this study. These patients were divided into two groups: the surgical staging group, comprising 58 patients who had received para-aortic and pelvic lymphadenectomy (surgical staging) along with concurrent chemoradiation therapy (CCRT), and the imaging staging group, comprising 113 patients who had received only CCRT. The two groups' progression-free survival (PFS), overall survival (OS) and treatment-related complications were compared. The surgical staging group started radiotherapy 10.2 days (range 9-12 days) later than the imaging staging group. The overall incidence of lymphatic cysts was 9.30%. In the surgical staging group, para-aortic lymph node metastasis was identified in 34.48% (20/58) of patients, while pathology-negative PLN was observed in 12.07% (7/58). Over a median follow-up period of 52 months, no significant differences in PFS and OS rates were found between the two groups (p > 0.05). Subgroup analysis of patients with lymph node diameters of ≥ 1.5 cm revealed a five-year PFS rate of 75.0% and an OS rate of 80.0% in the surgical staging group, compared to 41.5% and 50.1% in the imaging staging group, respectively, showing statistically significant differences (p = 0.022, HR:0.34 [0.13, 0.90] and p = 0.038, HR: 0.34 [0.12,0.94], respectively for PFS and OS). Additionally, in patients with two or more metastatic lymph nodes, the five-year PFS and OS rates were 69.2% and 73.1% in the surgical staging group, versus 41.0% and 48.4% in the imaging staging group, with these differences also being statistically significant (p = 0.025, HR: 0.41[0.19,0.93] and p = 0.046, HR: 0.42[0.18,0.98], respectively). Performing surgical staging before CCRT is safe and delivers accurate lymph node details crucial for tailoring radiotherapy. This approach merits further investigation, particularly in women with pelvic lymph nodes measuring 1.5 cm or more in diameter or patients with two or more imaging-positive PLNs.

Postoperative adjuvant therapy for stage IA-IIA cervical adenocarcinoma (FIGO 2018) with one intermediate-risk factor: a multicentre retrospective cohort study of 63,926 cases

Abstract Objective To compare the 5-year oncological outcomes of different adjuvant treatment modalities in patients with FIGO 2018 stage IA-IIA cervical adenocarcinoma who underwent open radical hysterectomy and one intermediate-risk pathological factor. Methods Based on the Four C database (between 2004 and 2018,n=63,926), patients with FIGO 2018 stage IA-IIA cervical adenocarcinoma and only one intermediate-risk pathological factor underwent open extensive hysterectomy. All patients were divided into three groups, namely, the simple surgery group (radical hysterectomy, RH), postoperative adjuvant chemotherapy group (radical hysterectomy and chemotherapy, RH + CT), and postoperative adjuvant chemoradiotherapy group (radical hysterectomy and radiotherapy/concurrent chemoradiotherapy, RH + RT/CCRT). The 5-year OS and DFS rates were compared among the three groups. Results Of the 219 cervical adenocarcinoma patients with only one intermediate-risk pathological factor, 50 patients had RH; 54 patients had RH + CT; and 115 patients had RH + RT/CCRT. There were no significant differences in 5-year OS and 5-year DFS rates among the three groups (RH vs. RH + CT: 92.7% vs. 90.3%, P = 0.749; 88.5% vs. 85.1%, P = 0.680, RH vs. RH + RT/CCRT: 90.7% vs. 82.3%, P = 0.484; 84.4% vs. 90.1%, P = 0.494, RH + CT vs. RH + RT/CCRT: 89.9% vs. 90.6%, P = 0.815; 90.5% vs. 90.8%, P = 0.905). Conclusion Postoperative adjuvant chemotherapy or chemoradiotherapy did not significantly improve the outcomes of FIGO 2018 IA-IIA cervical adenocarcinoma patients with only one intermediate risk factor.

Single-cell transcriptomics unveils multifaceted immune heterogeneity in early-onset versus late-onset cervical cancer

Early-onset (EOCC) and late-onset cervical cancers (LOCC) represent two clinically distinct subtypes, each defined by unique clinical manifestations and therapeutic responses. However, their immunological profiles remain poorly explored. Herein, we analyzed single-cell transcriptomic data from 4 EOCC and 4 LOCC samples to compare their immune architectures. Epithelial cells in EOCC exhibited a notable dual immunological phenotype, characterized by immune-suppressive properties driven by elevated CXCL production, alongside immune-stimulatory features linked to heightened HLA molecule expression. CD4 + and CD8 + T cells in LOCC demonstrated a heightened activation state, while NK cells exhibited diminished cytotoxicity. Macrophages in LOCC displayed enhanced polarization towards both M1 and M2 phenotypes, along with dendritic cells showing augmented antigen-presenting capacity. Regarding cancer-associated fibroblasts (CAFs), EOCC was enriched with inflammatory CAFs, whereas LOCC harbored a higher proportion of antigen-presenting CAFs. These findings reveal the multifaceted immune heterogeneity between EOCC and LOCC, underscoring the imperative for age-tailored immunotherapeutic strategies.

A nomogram model based on SII, AFR, and NLR to predict infectious complications of laparoscopic hysterectomy for cervical cancer

Abstract Background This study aimed to investigate the potential risk factors associated with postoperative infectious complications following laparoscopic hysterectomy for cervical cancer and to develop a prediction model based on these factors. Methods This study enrolled patients who underwent selective laparoscopic hysterectomy for cervical cancer between 2019 and 2024. A multivariate regression analysis was performed to identify independent risk factors associated with postoperative infectious complications. A nomogram prediction model was subsequently constructed and evaluated using R software. Results Out of 301 patients were enrolled and 38 patients (12.6%) experienced infectious complications within one month postoperatively. Six variables were independent risk factors for postoperative infectious complications: age ≥ 60 (OR: 3.06, 95% confidence interval (CI): 1.06–8.79, P = 0.038), body mass index (BMI) ≥ 24.0 (OR: 3.70, 95%CI: 1.4–9.26, P = 0.005), diabetes (OR: 2.91, 95% CI: 1.10–7.73, P = 0.032), systemic immune-inflammation index (SII) ≥ 830 (OR: 6.95, 95% CI: 2.53–19.07, P &lt; 0.001), albumin-to-fibrinogen ratio (AFR) &lt; 9.25 (OR: 4.94, 95% CI: 2.02–12.07, P &lt; 0.001), and neutrophil-to-lymphocyte ratio (NLR) ≥ 3.45 (OR: 7.53, 95% CI: 3.04–18.62, P &lt; 0.001). Receiver operator characteristic (ROC) curve analysis indicated an area under the curve (AUC) of this nomogram model of 0.928, a sensitivity of 81.0%, and a specificity of 92.1%. Conclusions The nomogram model, incorporating age, BMI, diabetes, SII, AFR, and NLR, demonstrated strong predictive capabilities for postoperative infectious complications following laparoscopic hysterectomy for cervical cancer.

Sarcoma of the uterine cervix: experience of a single center

Abstract Objectives To investigate the clinicopathological characteristics and prognosis of patients with primary sarcoma of the uterine cervix. Methods We identified all patients with primary cervical sarcomas treated at our institution from 2002 to 2020 and analyzed the clinicopathological characteristics and prognosis. Results 34 patients were identified, 7 (20.6%) patients had leiomyosarcoma, 6 (17.6%) had carcinosarcoma, 5 (14.7%) had Ewing sarcoma, 4 (11.8%) had rhabdomyosarcoma, 4 (11.8%) had undifferentiated sarcoma, 2 (5.9%) had adenosarcoma, 2 (5.9%) had endometrial stromal sarcoma, 1 (2.9%) had dermatofibrosarcoma protuberans, 1 (2.9%) had alveolar soft tissue sarcoma and 2 (5.9%) had sarcoma not otherwise specified. The median age of the whole patients was 43.5 years (range, 13–63). The median age of patients with Ewing sarcoma or rhabdomyosarcoma was 22 years (range, 13–39) and 17 years (range, 13–36 years), respectively. The distribution by stage was: stage I in 21 (61.8%) patients, stage II in 4 (11.8%), stage III in 6 (17.6%) and stage IV in 3 (8.8%). Overall, 30 patients (88.2%) received surgical treatment. The median follow-up was 33.3 months (range 3.6–187.3 months). 11 patients died within 2 years after diagnosis, most of them were patients with carcinosarcoma or undifferentiated sarcoma (45.5%, 5/11). In the entire cohort, 2- and 5-year OS were 67.2% and 56.9%, respectively. 5-year OS was 25.0% for undifferentiated sarcoma, 50.0% for rhabdomyosarcoma, 50.0% for carcinosarcoma, 53.3% for Ewing sarcoma, 57.1% for leiomyosarcoma. Conclusion Cervical sarcomas are rare neoplasms with multiple histological subtypes and follow an aggressive course. Prognosis may be associated with tumor histology and stage.

The role of complete cytoreductive surgery with hyperthermic intraperitoneal chemotherapy in ovarian carcinoma: where do we stand today? A comprehensive review and clinical insights from a leading oncology center in India

The current treatment for advanced epithelial ovarian cancer (EOC) is complete cytoreductive surgery (CRS) followed by adjuvant chemotherapy. Although many patients respond well to this treatment, many will relapse and die from peritoneal carcinomatosis. Adding Hyperthermic Intraperitoneal Chemotherapy (HIPEC) to the standard treatment has been shown to improve survival by reducing cancer recurrence in the abdomen, with acceptable side effects. This article summarizes the current evidence and our long experience with CRS and HIPEC at different stages of ovarian cancer treatment: at upfront CRS, at interval CRS, at secondary CRS, and as palliative setting. Our study cohort includes 400 EOC patients who underwent CRS only and CRS with HIPEC in upfront, interval, and secondary setting. Cisplatin 75mg/m For a median follow-up of 80 months, the DFS in CRS with HIPEC and CRS only were 34.3 months vs 22.7 months in the upfront group (p < 0.001), 18.9 months vs 13.3 months in the interval group, (p 0.04) and 14.7 months vs 11.9 months in secondary group, (p 0.13). The median OS in the CRS with HIPEC vs CRS only group was 72.1 months vs 43.3 months in the upfront setting, (p-value 0.034) and 54.2 months vs 44.7 months in the interval setting (p-value 0.44). At 5 years, 49% in the upfront setting and 28% in the interval setting were alive in the CRS with HIPEC arm. There was no difference in Clavien Dindo Grade 3 & 4 postoperative complications among both the groups except for days of hospital stay (p-value 0.016). Cytoreductive surgery (CRS) with HIPEC presently play a promising treatment strategy for advanced ovarian cancer, potentially enhancing outcomes compared to conventional therapies in all settings. Thus, adding HIPEC to complete cytoreductive surgery has improved outcomes in all required settings of advanced EOC especially in upfront setting.

A MRI radiomics-based model for prediction of pelvic lymph node metastasis in cervical cancer

Abstract Background Cervical cancer (CC) is a common malignancy of the female reproductive tract, and preoperative prediction of lymph node metastasis (LNM) is essential. This study aims to design and validate a magnetic resonance imaging (MRI) radiomics-based predictive model capable of detecting LNM in patients diagnosed with CC. Methods This retrospective analysis incorporated 86 and 38 CC patients into the training and testing groups, respectively. Radiomics features were extracted from MRI T2WI, T2WI-SPAIR, and axial apparent diffusion coefficient (ADC) sequences. Selected features identified in the training group were then used to construct a radiomics scoring model, with relevant LNM-related risk factors having been identified through univariate and multivariate logistic regression analyses. The resultant predictive model was then validated in the testing cohort. Results In total, 16 features were selected for the construction of a radiomics scoring model. LNM-related risk factors included worse differentiation ( P &lt; 0.001), more advanced International Federation of Gynecology and Obstetrics (FIGO) stages ( P = 0.03), and a higher radiomics score from the combined MRI sequences ( P = 0.01). The equation for the predictive model was as follows: −0.0493–2.1410 × differentiation level + 7.7203 × radiomics score of combined sequences + 1.6752 × FIGO stage. The respective area under the curve (AUC) values for the T2WI radiomics score, T2WI-SPAIR radiomics score, ADC radiomics score, combined sequence radiomics score, and predictive model were 0.656, 0.664, 0.658, 0.835, and 0.923 in the training cohort, while these corresponding AUC values were 0.643, 0.525, 0.513, 0.826, and 0.82 in the testing cohort. Conclusions This MRI radiomics-based model exhibited favorable accuracy when used to predict LNM in patients with CC. Relative to the use of any individual MRI sequence-based radiomics score, this predictive model yielded superior diagnostic accuracy.

Role of PARP inhibitors beyond BRCA mutation and platinum sensitivity in epithelial ovarian cancer: a meta-analysis of hazard ratios from randomized clinical trials

Abstract Background PARP inhibitors (PARPi) have a well-established role in platinum-sensitive ovarian cancer (PSOC), in BRCA mutant (BRCAm), and homologous recombination deficiency (HRD) population. However, their role in wild type and homologous recombination proficient population is still not clear. Methods A meta-analysis of hazard ratios (HR) of randomized control trials (RCTs) was conducted to study the role of PARPi. The published RCTs comparing the efficacy of PARP inhibitors alone or in combination with chemotherapy and/or target therapies versus placebo/chemotherapy alone/target therapy alone in primary or recurrent ovarian cancer settings were selected. Progression-free survival (PFS) and overall survival (OS) were the primary endpoints. Results A total of 14 primary studies and 5 updated studies are considered, consisting of 5363 patients. Overall, HR for PFS was 0.50 [95% CI 0.40–0.62]. HR of PFS was 0.94 [95% CI 0.76–1.15] in the PROC group, 0.41 [95% CI 0.29–0.60] was in HRD with BRCA unknown (BRCAuk), 0.38 [95% CI 0.26–0.57] in HRD with BRCAm, and 0.52 [95% CI 0.38–0.71] in HRD with BRCAwt. In the HRP group, overall HR for PFS was 0.67 [95% CI 0.56–0.80], 0.61 [95% CI 0.38–0.99] in HRD unknown with BRCA wt, and 0.40 [95% CI 0.29–0.55] in BRCAm HR for PFS. Overall, HR for OS was 0.86 [95% CI 0.73–1.031]. Conclusions The results suggest that PARPi have a meaningful clinical benefit in PSOC, HRD, BRACm, and also in HRP and PROC; however, the evidence is not sufficient to recommend their routine use and further studies are needed to expand their role in the HRP and PROC groups.

Impacts of ovarian preservation on the prognosis of neuroendocrine cervical carcinoma: a retrospective analysis based on machine learning

Abstract Background Neuroendocrine cervical carcinoma (NECC) is a rare but aggressive malignancy with younger patients compared to other common histology types. This study aimed to evaluate the impacts of ovarian preservation (OP) on the prognosis of NECC through machine learning. Methods Between 2013 and 2021, 116 NECC patients with a median age of 46 years received OP or bilateral salpingo-oophorectomy (BSO) and were enrolled in a retrospective analysis with a median follow-up of 41 months. The prognosis was estimated using Kaplan–Meier analysis. Random forest, LASSO, stepwise, and optimum subset prognostic models were constructed in training cohort (randomly selected 70 patients) and tested in 46 patients through receiver operator curves. Risk factors for ovarian metastasis were identified through univariate and multivariate regression analyses. All data processing was carried out in R 4.2.0 software. Results Among 116 patients, 30 (25.9%) received OP and showed no significantly different OS compared with BSO group (p = 0.072) and got better DFS (p = 0.038). After construction of machine learning models, the safety of OP was validated in lower prognostic risk group (p &gt; 0.05). In patients ≤ 46 years, no impacts of OP were shown for DFS (p = 0.58) or OS (p = 0.67), and OP had no impact on DFS in different relapse risk population (p &gt; 0.05). In BSO group, regression analyses showed that later stage, para-aortic LNM, and parametrial involvement were associated with ovarian metastasis (p &lt; 0.05). Conclusions Preserving ovaries had no significant impact on prognosis in patients with NECC. OP should be considered cautiously in patients with ovarian metastasis risk factors.

Cervical cancer with patent foramen ovale metastasis to the left ventricle: a case report

Metastasis of malignant tumors to the cardiac endocardium is rare and mainly involves the right side of the heart. It is extremely rare to involve the left cardiac endocardium, especially when there is neither pulmonary metastasis nor primary lung cancer, which we call "isolated" left cardiac endocardium metastasis in this paper. Few such cases previously reported in the literature were not screened for patent foramen ovale (PFO). This article reports a case of a young woman with a history of surgery for cervical cancer, who was transferred to our hospital with a suspected diagnosis of PFO after recent recurrent multiple cerebral infarctions. On admission, transthoracic echocardiography revealed multiple stringy vegetations in the left ventricle, which were subsequently removed surgically, with intraoperative confirmation of a patent foramen ovale and closure of it simultaneously. According to her medical history and pathological results, she was diagnosed with left ventricular metastasis of cervical cancer, a rare case of isolated left heart endocardium metastasis without previous pulmonary metastasis, presumably through the patent foramen ovale. PFO may play an important role in the process of isolated left heart endocardium metastasis in patients with distant malignancies and paradoxical embolism. Screening for PFO in high-risk patients may have significant clinical significance.

Gene signature and prognostic value of ubiquitination-related genes in endometrial cancer

AbstractProtein ubiquitination is closely related to tumor occurrence and development. The specific role of ubiquitination in endometrial cancer remains largely unclear. Therefore, we constructed a novel endometrial cancer prognostic model based on ubiquitination-related genes. We extracted the expression matrices of ubiquitination-related genes from the Cancer Genome Atlas database, upon which we performed univariate Cox regression and least absolute shrinkage and selection operator (LASSO) regression analyses to obtain 22 ubiquitination-related genes for the construction of the prognostic model. Survival, regression, clinical correlation, and principal component analyses were performed to assess the performance of the model. Drug sensitivity analysis was performed based on these ubiquitination-related genes. Finally, a prognostic nomogram was constructed based on the prognostic model to quantify patient outcomes. Survival, regression, clinical correlation, and principal component analyses revealed that the performance of the prognostic model was satisfactory. Drug sensitivity analysis provided a potential direction for the treatment of endometrial cancer. The prognostic nomogram could be used to effectively estimate the survival rate of patients with endometrial cancer. In summary, we constructed a new endometrial cancer prognostic model and identified 5 differentially expressed, prognosis-associated, ubiquitination-related genes. These 5 genes are potential diagnostic and treatment targets for endometrial cancer.

Enhancing precision medicine: a nomogram for predicting platinum resistance in epithelial ovarian cancer

Abstract Background This study aimed to develop a novel nomogram that can accurately estimate platinum resistance to enhance precision medicine in epithelial ovarian cancer(EOC). Methods EOC patients who received primary therapy at the General Hospital of Ningxia Medical University between January 31, 2019, and June 30, 2021 were included. The LASSO analysis was utilized to screen the variables which contained clinical features and platinum-resistance gene immunohistochemistry scores. A nomogram was created after the logistic regression analysis to develop the prediction model. The consistency index (C-index), calibration curve, receiver operating characteristic (ROC) curve, and decision curve analysis (DCA) were used to assess the nomogram’s performance. Results The logistic regression analysis created a prediction model based on 11 factors filtered down by LASSO regression. As predictors, the immunohistochemical scores of CXLC1, CXCL2, IL6, ABCC1, LRP, BCL2, vascular tumor thrombus, ascites cancer cells, maximum tumor diameter, neoadjuvant chemotherapy, and HE4 were employed. The C-index of the nomogram was found to be 0.975. The nomogram’s specificity is 95.35% and its sensitivity, with a cut-off value of 165.6, is 92.59%, as seen by the ROC curve. After the nomogram was externally validated in the test cohort, the coincidence rate was determined to be 84%, and the ROC curve indicated that the nomogram’s AUC was 0.949. Conclusion A nomogram containing clinical characteristics and platinum gene IHC scores was developed and validated to predict the risk of EOC platinum resistance.

Extraperitoneal laparoscopy for para-aortic lymphadenectomy in endometrial carcinoma staging: an approach with higher efficiency

Abstract Background Removing more inframesenteric nodes is not only significantly increases the likelihood of finding metastasis for endometrial cancer, but also can add survival advantage. As most patients diagnosed with endometrial cancer are overweight or obesity, a high efficiency approach is important. Aim of this study was to compare the surgical outcomes of extraperitoneal laparoscopic, transperitoneal laparoscopic, and laparotomic para-aortic lymphadenectomy in endometrial carcinoma staging. Methods We retrospectively reviewed data of all patients diagnosed with primary endometrial carcinoma who were treated at the Department of Gynecologic Oncology, Fudan University Shanghai Cancer Center from 1 January 2017 to 31 December 2019. The numbers of para-aortic lymph nodes, surgical time, complications, blood loss and hospital stay were compared. The patients’ medical records and pathological reports were carefully reviewed. Statistical significance was defined as p &lt; 0.05. Results We retrospectively compared patients who underwent extraperitoneal laparoscopy (Group E, n = 20), transperitoneal laparoscopy (group T, n = 21), and laparotomy (group L, n = 135). The median number of para-aortic lymph nodes was significantly higher in group E than in groups T and L (9.5, 5, and 6, respectively; p = 0.004 and 0.0004, respectively). All patients in group E underwent successfully dissection to the renal vessel level. The median operation time was significantly shorter in group L than in groups T and E (94, 174, and 233 min, respectively; p &lt; 0.0001). The median estimated blood loss volume was higher in group L than in groups T and E (200, 100, and 142.5 ml, respectively; all comparisons p &lt; 0.001), and the length of hospital stay was significantly longer in group L than in Groups T and E (6, 5, and 6 days, respectively; all comparisons p &lt; 0.001). Conclusion The extraperitoneal laparoscopic approach for staging endometrial carcinoma harvested higher numbers of para-aortic lymph nodes which could be considered for endometrial carcinoma staging, especially for para-aortic lymph node harvest.

Patterns of lymph node metastasis in level IIB and contralateral level VI for papillary thyroid carcinoma with pN1b and safety of low collar extended incision for neck dissection in level II

Abstract Objective To explore relevant clinical factors of level IIB and contralateral level VI lymph node metastasis and evaluate the safety of low-collar extended incision (LCEI) for lymph node dissection in level II for papillary thyroid carcinoma (PTC) with pN1b. Method A retrospective analysis was performed on 218 patients with PTC with pN1b who were treated surgically in the Head and Neck Surgery Center of Sichuan Cancer Hospital from September 2021 to May 2022. Data on age, sex, body mass index (BMI), tumor location, maximum tumor diameter, multifocality, Braf gene, T staging, surgical incision style, and lymph node metastasis in each cervical subregion were collected. The chi-square test was used for comparative analysis of relevant factors. All statistical analyses were completed by SPSS 24 software. Result Each subgroup on sex, age, BMI, multifocality, tumor location, extrathyroidal extension, Braf gene, and lymphatic metastasis in level III, level IV, and level V had no significant difference in the positive rate of lymph node metastasis in level IIB ( P  &gt; 0.05). In contrast, patients with bilateral lateral cervical lymphatic metastasis were more likely to have level IIB lymphatic metastasis than those with unilateral lateral cervical lymphatic metastasis, with a statistically significant difference ( P  = 0.000). In addition, lymph node metastasis in level IIA was significantly associated with lymph node metastasis in level IIB ( P  = 0.001). After multivariate analysis, lymph node metastasis in level IIA was independently associated with lymph node metastasis in level IIB ( P  = 0.010). The LCEI group had a similar lymphatic metastasis number and lymphatic metastasis rate in both level IIA and level IIB as the L-shaped incision group ( P  &gt; 0.05). There were 86 patients with ipsilateral central lymphatic metastasis (78.2%). Patients with contralateral central lymphatic metastasis accounted for 56.4%. The contralateral central lymphatic metastasis rate was not correlated with age, BMI, multifocality, tumor invasion, or ipsilateral central lymphatic metastasis, and there was no significant difference ( P  &gt; 0.05). The contralateral central lymphatic metastasis in males was slightly higher than that in females, and the difference was statistically significant (68.2% vs. 48.5%, P  = 0.041). Conclusion Lymphatic metastasis in level IIA was an independent predictor of lymphatic metastasis in level IIB. When bilateral lateral cervical lymphatic metastasis or lymph node metastasis of level IIA is found, lymph node dissection in level IIB is strongly recommended. When unilateral lateral cervical lymphatic metastasis and lymphatic metastasis in level IIA are negative, lymph node dissection in level IIB may be performed as appropriate on the premise of no damage to the accessory nerve. LCEI is safe and effective for lymph node dissection in level II. When the tumor is located in the unilateral lobe, attention should be given to contralateral central lymph node dissection because of the high lymphatic metastasis rate.

Analysis of outcomes following loop electrosurgical excision and clinical features of patients with cervical high-grade squamous intraepithelial lesions with abnormal preoperative endocervical curettage

Abstract Objective The purpose of this study was to identify the clinical characteristics of patients with high-grade squamous intraepithelial lesions (HSIL) with abnormal endocervical curettage (ECC) and to evaluate the efficacy of abnormal preoperative ECC in predicting recurrence after a loop electrosurgical excision procedure (LEEP). Methods We retrospectively analyzed a total of 210 cases of histological HSIL in female patients diagnosed using cervical biopsy and/or indiscriminating ECC, and these included 137 cases with normal ECC and 63 cases with abnormal ECC. We also collected preoperative information and data on postoperative human papillomavirus (HPV) and histological outcomes within 2 years. Results The additional detection rate of HSIL using indiscriminating ECC was 5%. Patients with abnormal ECC were older (P &lt; 0.001), predominantly menopausal (P = 0.001), had high-grade cytology (P = 0.032), a type 3 transformation zone (P = 0.046), and a higher proportion of HPV type 16/18 infection (P = 0.023). Moreover, age (odds ratio [OR] = 1.078, 95% confidence interval [CI] = 1.0325–1.1333, P = 0.003) and HPV 16/18 infection (OR = 2.082, 95% CI = 1.042–4.2163, P = 0.038) were independent risk factors for abnormal ECC. With an observed residual lesion/recurrence rate of 9.5% over the 24-month follow-up, we noted a 9.3% higher rate in the abnormal ECC group when compared with the normal ECC group. Abnormal preoperative ECC (OR = 4.06, 95% CI = 1.09–15.14, P = 0.037) and positive HPV at the 12-month follow-up (OR = 16.55, 95% CI = 3.54–77.37, P = 0.000) were independent risk factors for residual disease/recurrence. Conclusion Preoperative ECC was one of the risk factors for post-LEEP residual/recurrent HSIL, and detecting abnormal ECC when managing older patients or patients with HPV 16/18 infection during colposcopy is critical.

A prognostic model using FIGO 2018 staging and MRI-derived tumor volume to predict long-term outcomes in patients with uterine cervical squamous cell carcinoma who received definitive radiotherapy

Abstract Background Uterine cervical carcinoma is a severe health threat worldwide, especially in China. The International Federation of Gynecology and Obstetrics (FIGO) has revised the staging system, emphasizing the strength of magnetic resonance imaging (MRI). We aimed to investigate long-term prognostic factors for FIGO 2018 stage II–IIIC2r uterine cervical squamous cell carcinoma following definitive radiotherapy and establish a prognostic model using MRI-derived tumor volume. Methods Patients were restaged according to the FIGO 2018 staging system and randomly grouped into training and validation cohorts (7:3 ratio). Optimal cutoff values of squamous cell carcinoma antigen (SCC-Ag) and tumor volume derived from MRI were generated for the training cohort. A nomogram was constructed based on overall survival (OS) predictors, which were selected using univariate and multivariate analyses. The performance of the nomogram was validated and compared with the FIGO 2018 staging system. Risk stratification cutoff points were generated, and survival curves of low-risk and high-risk groups were compared. Results We enrolled 396 patients (training set, 277; validation set, 119). The SCC-Ag and MRI-derived tumor volume cutoff values were 11.5 ng/mL and 28.85 cm 3 , respectively. A nomogram was established based on significant prognostic factors, including SCC-Ag, poor differentiation, tumor volume, chemotherapy, and FIGO 2018 stage. Decision curve analysis indicated that the net benefits of our model were higher. The high-risk group had significantly shorter OS than the low-risk group in both the training ( p  &lt; 0.0001) and validation sets ( p  = 0.00055). Conclusions Our nomogram predicted long-term outcomes of patients with FIGO 2018 stage II–IIIC2r uterine cervical squamous cell carcinoma. This tool can assist gynecologic oncologists and patients in treatment planning and prognosis.

Survival outcomes of abdominal radical hysterectomy, laparoscopic radical hysterectomy, robot-assisted radical hysterectomy and vaginal radical hysterectomy approaches for early-stage cervical cancer: a retrospective study

Abstract Background This study compared the survival outcomes of abdominal radical hysterectomy (ARH) (N = 32), laparoscopic radical hysterectomy (LRH) (N = 61), robot-assisted radical hysterectomy (RRH) (N = 100) and vaginal radical hysterectomy (VRH) (N = 45) approaches for early-stage cervical cancer to identify the surgical approach that provides the best survival. Methods Disease-free survival (DFS) and overall survival (OS) were calculated using the Kaplan–Meier method, and survival curves were compared using the log-rank test. Results The volume of intraoperative blood loss was greater in the ARH group than in the LRH group, the RRH group or the VRH group [(712.50 ± 407.59) vs. (224.43 ± 191.89), (109.80 ± 92.98) and (216.67 ± 176.78) ml, respectively; P &lt; 0.001]. Total 5-year OS was significantly different among the four groups (ARH, 96.88%; LRH, 82.45%; RRH, 94.18%; VRH, 91.49%; P = 0.015). However, no significant difference in 5-year DFS was observed among the four groups (ARH, 96.88%; LRH, 81.99%; RRH, 91.38%; VRH, 87.27%; P = 0.061). Conclusion This retrospective study demonstrated that ARH and RRH achieved higher 5-year OS rates than LRH for early-stage cervical cancer.

Prognostic analysis of patients with stage IIIC1p cervical cancer treated by surgery

Abstract Background Cervical cancer (CC) is one of the most common gynaecologic malignancies. The prognosis of stage IIIC1p cervical cancer patients treated by surgery is heterogeneous. Therefore, the aim of this study was to analyse the factors influencing the prognosis in such patients. Methods From January 2012 to December 2017, 102 patients with cervical cancer who underwent surgical treatment in the Department of Gynaecology and Tumours, Changzhou Maternal and Child Health Hospital, and had pelvic lymph node metastasis confirmed by pathology were analysed retrospectively. All patients underwent radical hysterectomy with/without oophorectomy with pelvic lymphadenectomy with/without para-aortic lymphadenectomy. Clinical data was collected including age, surgical method, ovarian status, intraoperative blood loss, perioperative complications, tumour size, pathological type, depth of stromal invasion (DSI), whether the lymphatic vascular space was infiltrated, number of pelvic lymph node metastases, location of pelvic lymph node metastases, total number of lymph nodes resected, lymph node ratio (LNR), nature of vaginal margin, whether parametrium was involved, postoperative adjuvant therapy, preoperative neutrophil–lymphocyte ratio (NLR) and prognostic information of patients. Survival curves for overall survival (OS) and disease-free survival (DFS) were plotted using the Kaplan–Meier method, and the difference between the survival curves was tested using the log-rank test. Univariate and multivariate COX regression models were used to assess the factors associated with overall survival and disease-free survival in patients with stage IIIC1p cervical cancer. Nomogram plots were constructed to predict OS and DFS, and the predictive accuracy of the nomograms was measured by Harrell’s C-index and calibration curves. Results A total of 102 patients with stage IIIC1p cervical cancer were included in the study, and the median follow-up time was 63 months (range from 6 to 130 months). The 5-year OS was 64.7%, and the 5-year DFS was 62.7%. Multivariate analysis showed that no postoperative adjuvant therapy, LNR &gt; 0.3 and NLR &gt; 3.8 were independent risk factors for OS and DFS in patients with stage IIIC1p cervical cancer. Conclusions Patients with stage IIIC1p cervical cancer have a poor prognosis. Lower OS and DFS were associated with no postoperative adjuvant therapy, LNR &gt; 0.3 and NLR &gt; 3.8.

Effect of modified radical laparoscopic hysterectomy versus open radical hysterectomy on short-term clinical outcomes in early-stage cervical cancer: a single-center, prospective, randomized controlled trial

Abstract Background The long-term prognosis of minimally invasive surgery and open surgery for early cervical cancer is controversial. This study mainly discusses the feasibility and effectiveness of the endocutter in radical laparoscopic hysterectomy for early cervical cancer. Methods A single-center, prospective, randomized controlled trial of modified radical laparoscopic hysterectomy on patients with FIGO stage IA1 (lymphovascular invasion), IA2, and IB1 cervical cancer, between January 2020 and July 2021. Patients were randomly assigned into laparoscopic radical hysterectomy (LRH) and open radical hysterectomy (ORH) groups. The ORH group used right-angle sealing forceps for vaginal stump closure, whereas the LRH group used endoscopic staplers. The primary outcomes included the evaluation of the patient’s perioperative indicators, as well as short- and long-term complications. Recurrence and overall survival were considered secondary outcomes. Results As of July 2021, 17 patients were enrolled in the laparoscopic surgery group and 17 in the open surgery group. The hospitalization time of the laparoscopic group was significantly shorter than those of the open group (15 min vs. 9 min, P &lt; 0.001). The vaginal stump closure time in the laparoscopic group was longer than that in the open surgery group, and the difference was statistically significant (P &lt; 0.001). Post-operative catheter removal (P = 0.72), drainage tube removal time (P = 0.27), number of lymph node dissections (P = 0.72), and incidence of intraoperative and post-operative complications between the two groups (P &gt; 0.05). The median blood loss in the laparoscopic group was 278 ml, and it was 350 ml in the laparotomy group. The intraoperative blood transfusion rate was lower in the laparoscopic group; however, these differences did not reach statistical significance (P = 0.175). Vaginal margin pathology and peritoneal lavage cytology were negative, and all the patient’s vaginal stumps healed without infection. The median follow-up time of the laparoscopic group was 20.5 months, and it was 22 months for the open surgery group. There was no recurrence in all patients during the follow-up period. Conclusions Modified LRH with endocutter closure of the vaginal stump is an effective approach and not inferior to ORH in treating patients with early-stage cervical cancer. Trial registration ChiCTR2000030160, date of registration February 26, 2020 (https://www.chictr.org.cn/showprojen.aspx?proj=49809).

RETRACTED ARTICLE: miR-29c-3p regulates proliferation and migration in ovarian cancer by targeting KIF4A

Abstract Background Increasing evidence suggested that microRNA and kinesin superfamily proteins play an essential role in ovarian cancer. The association between KIF4A and ovarian cancer (OC) was investigated in this study. Methods We performed bioinformatics analysis in the GEO database to screen out the differentially expressed miRNAs (DEmiRNAs) associated with ovarian cancer prognosis. Upstream targeting prediction for KIF4A was acquired by using the mirDIP database. The potential regulatory factor miR-29c-3p for KIF4A was obtained from the intersection of the above all miRNAs. The prognosis of KIF4A and target-miRNA in OC was obtained in the subsequent analysis. qRT-PCR and Western blot detected KIF4A expression level in IOSE80 (human normal ovarian epithelial cell line). In the meantime, the gene expression level was detected in A2780, HO-8910PM, COC1, and SKOV3 cell lines (human ovarian carcinoma cell line). MTT and colony formation assays were used to detect cell proliferation of SKOV3 cell line. The following assays detected cell migration through the use of transwell and wound heal assays. Targeted binding relationship between KIF4A and miRNA was detected by using the dual-luciferase reporter assay. Results Both high expression of KIF4A and lower expression of miR-29c-3p could be used as biomarkers indicating poor prognosis in OC patients. Cellular function tests confirmed that when KIF4A was silenced, it inhibited the proliferation and migration of OC cells. In addition, 3′-UTR of KIF4A had a direct binding site with miR-29c-3p, which indicated that the expression of KIF4A could be regulated by miR-29c-3p. In subsequent assays, the proliferation and migration of OC cells were inhibited by the overexpression of miR-29c-3p. At the same time, rescue experiments also confirmed that the promotion of KIF4A could be reversed by miR-29c-3p. Conclusion In a word, our data revealed a new mechanism for the role of KIF4A in the occurrence and development of OC.

Proline-rich protein 11 overexpression is associated with a more aggressive phenotype and poor overall survival in ovarian cancer patients

Abstract Background The proline-rich protein 11 (PRR11) is a newly identified oncogene associated with a poor prognosis in several human cancers. Nonetheless, research on its role in ovarian cancer (OC) remains largely understudied. Therefore, this study aims to evaluate the expression levels of PRR11 protein and its role in human ovarian cancer. Methods Immunohistochemistry analysis was used to evaluate the expression levels of PRR11 protein in human samples obtained from 49 patients diagnosed with OC and subjected to curative surgery in the First Affiliated Hospital of Wenzhou Medical University between 2007 and 2015. Results In total, 57.1% of the primary OC tumor tissue evaluated demonstrated overexpression of PRR11. Meanwhile, the survival analysis showed that the overall survival (OS) of patients presenting overexpression of PRR11 was significantly lower than the OS of the patients with negative PRR11. In subsequent experiments, it was found that silencing the expression of PRR11 expression inhibited the proliferation of tumor cells and the migration of cells in vitro. Further, cells subjected to PRR11 knockdown exhibited a decrease in tumor growth in vivo. The downregulation of PRR11 was coupled with a decrease in N-cadherin and downregulation in the expression of early growth response protein 1 (EGR1). Conclusions The findings suggest that PRR11 might be considered as a potential target for prognostic assessment and gene therapy strategies for patients diagnosed with OC.

Prognostic prediction of systemic immune-inflammation index for patients with gynecological and breast cancers: a meta-analysis

Abstract Background Systemic immune-inflammation index (SII) has been suggested to be effective to reflect the inflammatory status and thus may be an underlying biomarker for prognosis prediction. This hypothesis has been demonstrated in meta-analyses on several cancer types. However, there was no study to confirm the prognostic roles of SII for gynecological and breast cancers, which was the goal of our study. Methods PubMed, EMBASE, and Cochrane Library databases were searched to collect the articles exploring the associations of SII with prognostic outcomes [overall survival (OS), disease-free survival (DFS), progression-free survival (PFS), lymph node metastasis (LNM), and lymphovascular invasion (LVI)] in gynecological and breast cancers. The prognostic value of SII was estimated by hazard ratio (HR) or relative risk (RR) with 95% confidence interval (CI). Results Nine articles involving 2724 patients in 11 datasets were included. Meta-analysis showed that a high SII index was significantly associated with poor OS (HR = 2.12, 95% CI, 1.61–2.79, P &lt; 0.001), DFS/PFS (HR = 2.28, 95% CI 1.52–3.41, P &lt; 0.001) and an increased risk for LNM (RR = 1.34, 95% CI 1.20–1.50, P &lt; 0.001) in patients with gynecological and breast cancers. Subgroup analysis confirmed the prognostic role of SII for OS was applicable to all cancer types, but the association with DFS/PFS and LNM was only significant for ovarian cancer and breast cancer, especially triple-negative breast cancer. No significant association was detected between SII and LVI. Conclusion High SII may be a promising indicator for the prediction of poor prognosis in patients with gynecological and breast cancers, especially ovarian cancer and triple-negative breast cancer.

Secondary surgical cytoreduction needs to be assessed taking into account surgical technique, completeness of cytoreduction, and extent of disease

AbstractRecent evidence suggested that secondary surgical cytoreduction followed by chemotherapy does not result in longer overall survival in patients with platinum-sensitive recurrent ovarian cancer.This statement is based on a phase III multicenter, randomized clinical trial that lacks a description of the surgical protocol, the surgical technique, and the surgical variables. In a study that evaluates surgical cytoreduction, it is mandatory to assess the grade of cytoreductive surgery achieved (Sugarbaker PH, Langenbeck’s Arch Surg 384:576–87, 1999), the extent of disease using PCI (Peritoneal Cancer Index), the technique itself, and the existence of a multidisciplinary approach with extensive upper abdominal procedures in experienced centers (Ren et al, BMC Cancer 15:1-12, 2015). There is evidence proving that the quality of cytoreduction (Al Rawahi et al, Cochrane Database Syst Rev 2013, 2013), the measurement of the amount of disease by PCI (Elzarkaa et al, J Gynecol Oncol 29, 2018), and a multidisciplinary approach with supramesocolic procedures (Ren et al, BMC Cancer 15:1-12, 2015) impact overall survival.This study fails to compare chemotherapy with secondary cytoreductive surgery since, due to the lack of variables, we can assess neither the performed surgery nor its criteria. This study should not be taken into account to recommend chemotherapy alone over a surgical approach in this group of patients.

Evaluation of a novel ovarian cancer-specific fluorescent antibody probe for targeted near-infrared fluorescence imaging

Abstract Background To meet clinical needs, fluorescence-guided surgery has emerged as a new technique that guides surgeons in the resection of cancerous tissue by highlighting tumour lesions during surgery. We aimed to evaluate the novel ovarian cancer-specific antibody fluorescent probe COC183B2-800 (COC183B2 conjugated with IRDye800CW) in tumour-specific imaging to determine if it can help surgeons remove malignant lesions under fluorescence guidance. Methods The expression of OC183B2 antigen in epithelial ovarian cancer (EOC) tissues and cell lines was determined using immunohistochemistry (IHC). Western blotting was used to verify the expression of OC183B2 in SKOV3-Luc tumours. Antibodies against OC183B2 and mouse immunoglobulin G1 (IgG1) were conjugated with IRDye800CW to develop the antibody fluorescent probes COC183B2-800 and IgG-800 (immunoglobulin G1 conjugated with IRDye800CW). A subcutaneous mouse tumour model of SKOV3-Luc cells was constructed. Bioluminescent imaging (BLI) was conducted to detect the tumour location. Near-infrared fluorescence (NIRF) imaging was performed after the mice were injected with imaging agents. The mice were sacrificed 96 h postinjection, and the biodistribution assays were performed using NIRF imaging. Results In 69 EOC patients, the total positive rate of OC183B2 in EOC tissues was 89.9% (62/69). Expression of the OC183B2 antigen was positive in SKOV3-Luc, 3AO, ES2 and A2780 cells. The OC183B2 antigen could be detected in SKOV3-Luc tumours. NIRF imaging of the COC183B2-800 probe at different doses showed a high fluorescent signal at the tumour location that was in line with the site detected by bioluminescent imaging. The tumour background ratio (TBR) was significantly higher in the COC183B2-800 group than in the IgG-800, IRDye800CW and PBS groups. The fluorescent probe COC183B2-800 is metabolized mainly through the liver and does not accumulate in other organs. Conclusions COC183B2-800 shows effective tumour-specific targeting of EOC and is a promising diagnostic and therapeutic tool for fluorescence-guided surgery.

Laparoscopic nerve‑sparing radical hysterectomy for the treatment of cervical cancer: a meta-analysis of randomized controlled trials

Abstract Background The effects and safety of laparoscopic nerve‑sparing radical hysterectomy (LNSRH) and laparoscopic radical hysterectomy (LRH) in cervical cancer treatment remain unclear. This article aims to evaluate the role of LNSRH versus LRH in the treatment of cervical cancer. This is because the updated meta-analysis with synthesized data may provide more reliable evidence on the role of LNSRH and LRH. Methods We searched Pubmed et al. databases for randomized controlled trials (RCTs) involving laparoscopic nerve‑sparing radical hysterectomy (LNSRH) and laparoscopic radical hysterectomy (LRH) for cervical cancer treatment from the inception of databases to June 15, 2021. The RevMan 5.3 software was used for data analyses. This meta-analysis protocol had been registered online (available at: https://inplasy.com/inplasy-2021-9-0047/). Results Thirteen RCTs involving a total of 1002 cervical cancer patients were included. Synthesized results indicated that the duration of surgery of the LNSRH group was significantly longer than that of the LRH group [SMD 1.11, 95% CI (0.15 ~ 2.07), P = 0.02]. The time to intestinal function recovery [SMD −1.27, 95% CI (−1.84 ~ −0.69), P &lt; 0.001] and the time to postoperative urinary catheter removal of the LNSRH group [SMD −1.24, 95% CI (−1.62 ~ −0.86), P &lt; 0.001] were significantly less than that of the LRH group. There were no significant differences in the estimated blood loss [SMD 0.10, 95% CI (−0.14 ~ 0.34), P = 0.41], the length of parauterine tissue resection [SMD −0.10, 95% CI (−0.25 ~ 0.05), P = 0.19], length of vaginal excision [SMD 0.04, 95% CI (−0.26 ~ 0.34), P = 0.78], and incidence of intraoperative adverse events [RR 0.97, 95% CI (0.44 ~ 2.13), P = 0.94] between the LNSRH group and the LRH group. Conclusions LNSRH significantly results in earlier bladder and bowel function after surgery. Limited by sample size, LNSRH should be considered with caution in the future.

Textbook outcome in ovarian cancer and its impact on survival: comparative study

Patients who achieve the textbook outcome (TO) present an uneventful postoperative course. Obtaining TO has also been related to better survival in oncological patients. Information about TO in patients with peritoneal carcinomatosis from ovarian cancer who undergo surgery is very scarce. Our objective was investigate TO in patients with carcinomatosis of ovarian origin who underwent interval surgery with or without HIPEC (TOOC) and its impact on survival. A multicenter study was performed between 2010 and 2015. Inclusion criteria were > 18 years old, with ovarian cancer and peritoneal carcinomatosis, who underwent scheduled surgery after response to neoadjuvant therapy. The criteria to establish TOOC were no major complications, no mortality, non-prolonged stay (p75:10 days), complete cytoreduction (CC-0), and no readmission. 365 patients were included, and TOOC was achieved in 204 (55.9%) patients. CC-0 cytoreduction was obtained in 312(85.5%). 7 patients (1.9%) died. 71 (19.5%) presented major complications (≥ IIIa). The readmission rate was 9.3%, and 24.9% of the patients presented a prolonged stay. The parameter with most significant negative impact on achieving TOOC was length of stay. Multivariate analysis confirmed postsurgical PCI, age, HIPEC, and time of surgery in minutes as an independent factor of TOOC. Survival analysis showed that patients who achieved TOOC had better overall survival (41 months (24.5- 67) versus 27 months (14-48.2) (p < 0.0001). TO is an easy and valuable management tool for evaluating and comparing results obtained at different centers after surgery for peritoneal carcinomatosis of locally advanced ovarian cancer. Achieving TOOC benefits overall survival.

Screening of CXC chemokines in the microenvironment of ovarian cancer and the biological function of CXCL10

Abstract Background This study aims to screen and identify the biological functions and prognostic value of CXC chemokines in ovarian cancer (OC) through bioinformatics and molecular biology methods, and to provide data support for the selection of biomarkers and prognostic analysis of OC. Methods In this study, GEO, ONCOMINE, GEPIA, cBioPortal, GeneMANIA, Metascape, STRING, TRRUST, and TIMER databases were used to study CXC chemokines. Angiogenesis and T cell killing assay were used to detect the effect of CXCL10 on tumor cell immunity and angiogenesis. Real-time quantitative PCR (qRT-PCR), immunoblotting, and ectopic tumor formation experiments were used to verify the effect of CXCL10 on ovarian cancer tumors. Results We found that CXCL1, CXCL10, CXCL11, CXCL13, and CXCL14 were significantly upregulated in OC samples compared with normal tissues. Our data showed that there was a relationship between the expression of CXC chemokines and the infiltration of six types of immune cells significant correlation. In vitro assay confirmed that overexpression of CXCL10 could enhance the killing effect of T cells and inhibit angiogenesis. Further in vivo assay had shown that CXCL10 could affect the progression of ovarian cancer by increasing the expression of cytotoxic T cells and inhibiting angiogenesis. Conclusion In conclusion, we hope that our data will provide new insights into the development of immunotherapy and the selection of prognostic markers for patients with OC.

Long non-coding RNA SDCBP2-AS1 delays the progression of ovarian cancer via microRNA-100-5p-targeted EPDR1

Abstract Background Dysregulation of long non-coding RNAs has been implied to connect with cancer progression. This research was to decipher the mechanism of long non-coding RNA SDCBP2-AS1 in ovarian cancer (OC) through regulation of microRNA (miR)-100-5p and ependymin-related protein 1 (EPDR1). Methods LncRNA SDCBP2-AS1 and EPDR1 levels in OC were assessed by Gene Expression Profiling Interactive Analysis. lncRNA SDCBP2-AS1, miR-100-5p, and EPDR1 levels in OC tissues and cells were determined. SKOV3 and A2780 cells were transfected with lncRNA SDCBP2-AS1, miR-100-5p, and EPDR1-related plasmids or sequences, and then their functions in cell viability, apoptosis, migration, and invasion were evaluated. The interplay of lncRNA SDCBP2-AS1, miR-100-5p, and EPDR1 was clarified. Results LncRNA SDCBP2-AS1 and EPDR1 levels were suppressed whilst miR-100-5p level was elevated in OC. After upregulating lncRNA SDCBP2-AS1 or EPDR1, viability, migration, and invasion of OC cells were impaired, and apoptosis rate was increased. Downregulating EPDR1 or upregulating miR-100-5p partially mitigated upregulated lncRNA SDCBP2-AS1-induced impacts on the biological functions of OC cells. LncRNA SDCBP2-AS1 sponged miR-100-5p, and EPDR1 was targeted by miR-100-5p. Conclusion It is illustrated that lncRNA SDCBP2-AS1 regulates EPDR1 by sponge adsorption of miR-100-5p to inhibit the progression of OC.

Salpingo-oophorectomy versus cystectomy in patients with borderline ovarian tumors: a systemic review and meta-analysis on postoperative recurrence and fertility

Abstract Background To compare the postoperative recurrence and fertility in patients with borderline ovarian tumors (BOTs) who underwent different surgical procedures: salpingo-oophorectomy versus cystectomy. Methods Potentially relevant literature from inception to Nov. 06, 2020, were retrieved in databases including Cochrane Library, EMBASE (Ovid), and MEDLINE (Pubmed). We applied the keywords “fertility-sparing surgery,” or “conservative surgery,” or “cystectomy,” or “salpingo-oophorectomy,” or “oophorectomy,” or “adnexectomy,” or “borderline ovarian tumor” for literate searching. Systemic reviews and meta-analyses were performed on the postoperative recurrence rates and pregnancy rates between patients receiving the two different surgical methods. Begger’s methods, Egger’s methods, and funnel plot were used to evaluate the publication bias. Result Among the sixteen eligible studies, the risk of recurrence was evaluated in all studies, and eight studies assessed the postoperative pregnancy rates in the BOT patients. A total of 1839 cases with borderline ovarian tumors were included, in which 697 patients (37.9%) received unilateral salpingo-oophorectomy and 1142 patients (62.1%) underwent unilateral/bilateral cystectomy. Meta-analyses showed that BOT patients with unilateral/bilateral cystectomy had significantly higher recurrence risk (OR=2.02, 95% CI: 1.59-2.57) compared with those receiving unilateral salpingo-oophorectomy. Pooled analysis of four studies further confirmed the higher risk of recurrence in patients with cystectomy (HR=2.00, 95% CI: 1.11-3.58). In addition, no significant difference in postoperative pregnancy rate was found between patients with the two different surgical procedures (OR=0.92, 95% CI: 0.60-1.42). Conclusion Compared with the unilateral/bilateral cystectomy, the unilateral salpingo-oophorectomy significantly reduces the risk of postoperative recurrence in patients with BOT, and it does not reduce the pregnancy of patients after surgery. Trial registration PROSPERO CRD42021238177

The prevalence, risk factors, and prognostic value of venous thromboembolism in ovarian cancer patients receiving chemotherapy: a systematic review and meta-analysis

AbstractBackgroundVenous thromboembolism (VTE) in ovarian cancer (OC) patients has been widely investigated, but our knowledge on the role of VTE in OC patients receiving chemotherapy is limited. The aim of our study was to investigate the prevalence, risk factors, and prognostic value of chemotherapy-associated VTE in OC.MethodsThree databases (PubMed, Embase, and the Cochrane Library) were systematically searched from inception to October 14, 2020. The primary outcome was the prevalence of VTE in OC patients receiving chemotherapy. The risk factors and prognostic value of VTE were the secondary outcomes. The pooled prevalence of VTE was estimated using the generic inverse-variance method. The statistical heterogeneity was evaluated with Cochran’sQtest andI2statistic. Funnel plot, Begg’s test, and Egger’s test were used to assess the potential publication bias in the meta-analysis.ResultsA total of eleven observational studies with 4759 OC patients were included. The pooled prevalence of VTE was 9% (95% CI, 0.06–0.12) in OC patients receiving chemotherapy. The results of subgroup analysis and sensitivity analysis were basically consistent with the overall pooled estimate. Multiple significant risk factors associated with VTE were also identified including advanced age, D-dimer &gt; 0.5 mg/mL, and tumor diameter &gt; 10 cm. Only two included studies reported the prognostic value of VTE in OC patients receiving chemotherapy, but with inconsistent results. Funnel plot showed that there existed potential publication bias, which was further verified by statistical test, but the results of the trim-and-fill method showed the pooled estimate kept stable after adding two “missing” studies.ConclusionsThis current study revealed that the pooled prevalence of chemotherapy-related VTE in OC was approximately 9% in OC patients. Risk factors for chemotherapy-related VTE were also identified which may contribute to targeting potentially preventative measures for VTE in OC.

Lymphadenectomy in ovarian cancers: a meta-analysis of hazard ratios from randomized clinical trials

AbstractBackgroundThe debate surrounding systematic lymphadenectomy in the epithelial cancers of the ovary (EOC) was temporarily put to rest by the LION trial. However, there was a glaring disparity between the number of patients registered and the number of patients randomized suggesting inadvertent selection. A subsequent meta-analysis after this trial included all types of studies in the literature (randomized, non-randomized, case series, and, retrospective cohort), thus diluting the results.MethodsWe conducted a meta-analysis of hazard ratios of randomized controlled trials, to study the role of systematic para-aortic and pelvic lymph node dissection in the EOC. A detailed search of MEDLINE, Cochrane, and Embase databases was done to look for the published randomized controlled trials (RCT) comparing lymphadenectomy versus no lymphadenectomy in EOC. A meta-analysis of hazard ratios (HR) was performed for overall survival (OS) and progression-free survival (PFS) using fixed and random effect models. The quality of the RCTs was evaluated on Jadad’s score, and the risk of bias was estimated by the Cochrane tool.ResultsA total of 1342 patients with EOC were included for quantitative analysis. On meta-analysis, HR for PFS was 0.9 (95% CI 0.79–1.04) favoring lymphadenectomy. HR for OS was 1 (95% CI 0.84–1.18) signifying no benefit of systematic lymphadenectomy.ConclusionThe results show a trend towards increased PFS which did not reach statistical significance nor translate into any meaningful benefit in OS. There is still a need for a greater number of well-conducted, suitably powered trials to convincingly answer this question.

Identification of a novel circ_0018289/miR-183-5p/TMED5 regulatory network in cervical cancer development

Abstract Background Circular RNAs (circRNAs) are increasingly implicated in regulating human carcinogenesis. Previous work showed the oncogenic activity of circ_0018289 in cervical cancer. However, the molecular basis underlying the modulation of circ_0018289 in cervical carcinogenesis is still not fully understood. Methods The levels of circ_0018289, microRNA (miR)-183-5p, and transmembrane p24 trafficking protein 5 (TMED5) were measured by quantitative real-time polymerase chain reaction (qRT-PCR) or western blot assay. Ribonuclease (RNase) R and subcellular localization assays were used to characterize circ_0018289. Cell proliferation was detected by the Cell Counting Kit-8 (CCK-8) and 5-ethynyl-2′-deoxyuridine (Edu) assays. Cell apoptosis and tube formation were assessed by flow cytometry and tube formation assays, respectively. A dual-luciferase reporter assay was performed to confirm the direct relationship between miR-183-5p and circ_0018289 or TMED5. The role of circ_0018289 in tumor growth was gauged by mouse xenograft experiments. Results Circ_0018289 was overexpressed in cervical cancer tissues and cells. Circ_0018289 silencing impeded cell proliferation, enhanced cell apoptosis, and suppressed angiogenesis in vitro, as well as diminished tumor growth in vivo. Mechanistically, circ_0018289 targeted and regulated miR-183-5p by binding to miR-183-5p, and circ_0018289 regulated cervical cancer development and angiogenesis partially through miR-183-5p. Moreover, TMED5 was directly targeted and inhibited by miR-183-5p through the perfect complementary sites in TMED5 3′UTR, and TMED5 knockdown phenocopied miR-183-5p overexpression in suppressing cervical cancer development and angiogenesis. Furthermore, circ_0018289 induced TMED5 expression by competitively binding to shared miR-183-5p. Conclusion Our observations identified the circ_0018289/miR-183-5p/TMED5 regulatory network as a novel molecular basis underlying the modulation of cervical carcinogenesis.

Neoadjuvant chemotherapy combined with radical surgery for stage IB2/IIA2 cervical squamous cell carcinoma: a prospective, randomized controlled study of 35 patients

Abstract Objective This study aimed to evaluate the clinical outcomes for patients with stage IB2/IIA2 cervical squamous cell carcinoma treated with neoadjuvant chemotherapy combined with radical surgery. Methods A total of 68 patients with cervical squamous cell carcinoma were randomly divided into the experimental group ( n = 35) and the control group ( n = 33). The patients in the experimental group received paclitaxel plus cisplatin neoadjuvant chemotherapy for two cycles, then underwent radical hysterectomy and bilateral adnexectomy at 2 weeks post-chemotherapy. The control group only underwent radical hysterectomy and bilateral adnexectomy after the diagnosis of cervical squamous cell carcinoma. The toxic and side effects of chemotherapy in the experimental group were observed. Also, the operation method, operation time, blood loss, grade of wound healing, complications, and postoperative pathology were noted in the two groups. Primary foci and pelvic lymph node recurrence and distant metastasis were observed, and 3-year and 5-year survival rates were calculated. Results Only one patient in the experiment had grade III bone marrow suppression; no other grade III and IV chemotherapy toxic reactions were observed. The operation was successfully completed in all patients. The operation time, intraoperative blood loss, placement of the ureteral catheter, bladder injury, ureteric injury, postoperative urinary tub, pelvic drainage tube indwelling time, anal exhaust time, postoperative complications, and metastatic ratio of lymph nodes were not significantly different between the two groups ( P &gt; 0.05). The number of dissected lymph nodes, deep myometrial invasion, and vascular tumor emboli showed a significant difference in the experimental group compared with the control group ( P &lt; 0.05). The 3-year disease-free survival (82.9% vs 81.9%), 5-year disease-free survival (71.4% vs 60.6%), 3-year overall survival (91.4% vs 87.8%), and 5-year overall survival (82.9% vs 75.6%) were not statistically significantly different between the experimental group and the control group ( P &gt; 0.05). Conclusions Neoadjuvant chemotherapy in IB2/IIA2 stage cervical squamous cell carcinoma showed low toxic side effects. Radical surgery after chemotherapy is safe and feasible. It plays a coordinating role in reducing the tumor infiltration depth of the deep muscle layer and the incidence of vascular tumor emboli, reducing the use of postoperative adjuvant therapy, and improving the quality of life of patients, but does not improve the 3-year/5-year survival rate.

The impacts of minimally invasive surgery on intermediate- or high-risk cervical cancer patients received adjuvant radiotherapy

Abstract Background Adjuvant chemoradiotherapy (CRT) has been shown to reduce the risk of recurrence for patients with risk factors after radical hysterectomy (RH). Early initiated CRT could result in superior oncological outcomes. Here, we aimed to compare the survival outcome of intermediate- or high-risk cervical cancer (CC) patients who, received adjuvant CRT between minimally invasive surgery (MIS) and open surgery. Methods Data on stage IB1-IIA2 patients who underwent RH and postoperative CRT in our institution, from 2014 to 2017, were retrospectively collected. Patients with high or intermediate-risk factors who met the Sedlis criteria received sequential chemoradiation (SCRT). According to the surgical approaches, the enrolled patients were divided into MIS and open surgery groups. Then, the disease-free survival (DFS), overall survival (OS), and prognostic factors were analyzed. Results Among 129 enrolled CC patients, 68 received open surgery and 61 received MIS. The median time interval from surgery to chemotherapy and to radiotherapy was shorter in the MIS group (7 days vs. 8 days, P=0.014; 28 days vs. 35, P&lt;0.001). Three-year DFS and OS were similar in both groups (85.2% vs. 89.7%, P=0.274; 89.9% vs. 98.5%, P=0.499). Further, sub-analysis indicated that the DFS and OS in intermediate/high-risk groups had no significant difference. Cox-multivariate analyses found that tumor size &gt;4 cm and time interval from surgery to radiotherapy beyond 7 weeks were adverse independent prognostic factors for DFS. Conclusion Based on the population we studied, for early-stage (IB1-IIA2) CC patients with intermediate- or high-risk factors who received postoperative SCRT, although the difference was not significant, the DFS and OS in the MIS group were slightly lower than the ORH group, and tumor size &gt;4 cm and delayed adjuvant radiotherapy beyond 7 weeks were risk factors for recurrence.

Comparative single-center study between modified laparoscopic radical hysterectomy and open radical hysterectomy for early-stage cervical cancer

Abstract Background Since the release of the LACC trial results in 2018, the safety of laparoscopic radical hysterectomy (LRH) for cervical cancer has received huge attention and heated discussion. We developed modified laparoscopic radical hysterectomy (MLRH) incorporating a series of measures to prevent tumor spillage, which has been performed in our center since 2015. Objective Present study retrospectively analyzed relevant indicators of MLRH and evaluated disease-free survival (DFS) primarily in the treatment of early cervical cancer compared with open surgery. Methods Patients with 2014 International Federation of Gynecology and Obstetrics clinical stages 1B1 and 2A1 cervical cancer who underwent radical hysterectomy in the gynecological department of our hospital from October 2015 to June 2018 were enrolled retrospectively in this study. Patients were divided into two groups based on the surgical procedure: open radical hysterectomy (ORH) group (n = 336) and MLRH group (n = 302). Clinical characteristics, surgical indices, and survival prognosis were analyzed, including 2.5-year overall survival (OS) rate, 2.5-year DFS rate, recurrence rate, and recurrence pattern. Results Compared to the ORH group, the MLRH group exhibited a longer operative time, longer normal bladder function recovery time, less intraoperative blood loss volume, and more harvested pelvic lymph nodes (P &lt; 0.05). No significant differences were observed in postoperative complications, the 2.5-year OS, 2.5-year DFS, and recurrence rate between the two groups (P &gt; 0.05); however, the recurrence pattern was significantly different (P &lt; 0.05). The MLRH group mainly exhibited local single metastasis (7/11), whereas the ORH group mainly exhibited distant multiple metastases (14/16). Stratified analysis revealed that overall survival rate was higher in the MLRH group than in the ORH group in patients with stage 1B1 and middle invasion (P &lt; 0.05). Conclusion MLRH does not show a survival disadvantage in the treatment of early-stage cervical cancer when compared with open surgery. In addition, MLRH shows a survival advantage in patients with stage 1B1 and middle 1/3 invasion. Considering this is a retrospective study, further prospective study is necessary for more sufficient data support. Trial registration Present research is a retrospective study. The study had retrospectively registered on Chinese Clinical Trial Registry (http://www.chictr.org.cn/), and the registered number is ChiCTR1900026306.

The comparative study for survival outcome of locally advanced cervical cancer treated by neoadjuvant arterial interventional chemotherapy or intravenous chemotherapy followed by surgery or concurrent chemoradiation

Abstract Objective This study aimed to compare the survival outcome of 3 different treatment groups (arterial interventional chemotherapy or intravenous chemotherapy or concurrent chemoradiotherapy) for locally advanced cervical cancer. Methods A total of 187 patients with pathological stage IB3–IIB cervical cancer (cervical squamous cell carcinoma, adenosquamous carcinoma, or adenocarcinoma) hospitalized in the First Affiliated Hospital of Zhengzhou University from January 2013 to May 2019 were included. Therefore, this article is a retrospective study. We collected data from all eligible patients. And all according to the treatment methods at that time, they were divided into three subgroups: (1) 40 patients who received neoadjuvant arterial interventional chemotherapy + surgery + postoperative chemotherapy (IA-NAC + RS), (2) 63 patients who received neoadjuvant intravenous chemotherapy + surgery + postoperative chemotherapy (IV-NAC + RS), (3) 84 patients who only received concurrent chemoradiotherapy (CCRT). Notably, 108 of these patients met the 5-year follow-up period, and 187 patients met the 3-year follow-up period only. Consequently, we compared 5-year survival and 3-year survival separately. The prognosis (5-year survival and 3-year survival) of the three groups and the chemotherapy efficacy, intraoperative blood loss, operation time, and postoperative pathological risk factors of different subgroups were compared. Results (1) There were no significant differences in the 3-year overall survival (OS) rate, 3-year progression-free survival (PFS) rate, 5-year OS rate, and 5-year PFS rate among the three subgroups (p &gt; 0.05). (2) The chemotherapy response rates of IA-NAC+RS group (37.5%) and IV-NAC+RS group (25.4%) were comparable (p &gt; 0.05). (3) The intraoperative blood loss in the IA-NAC+RS group (average 92.13±84.09 mL) was significantly lower than that in the IV-NAC+RS group (average 127.2±82.36 mL) (p &lt; 0.05). (4) The operation time of the IA-NAC+RS group (average 231.43±63.10 min) and the IV-NAC+RS group (average 219.82±49.11 min) were comparable (p &gt; 0.05). (5) There were no significant differences between the IA-NAC+RS group and IV-NAC+RS group in pathological lymph node metastasis, parametrial invasion, and involvement of lymphovascular space (p &gt; 0.05). Conclusions Neoadjuvant chemotherapy combined with surgery had the same long-term survival benefit as concurrent chemoradiotherapy.

Identification of a necroptosis-related prognostic gene signature associated with tumor immune microenvironment in cervical carcinoma and experimental verification

AbstractCervical carcinoma (CC) has been associated with high morbidity, poor prognosis, and high intratumor heterogeneity. Necroptosis is the significant cellular signal pathway in tumors which may overcome tumor cells’ apoptosis resistance. To investigate the relationship between CC and necroptosis, we established a prognostic model based on necroptosis-related genes for predicting the overall survival (OS) of CC patients. The gene expression data and clinical information of cervical squamous cell carcinoma and endocervical adenocarcinoma (CESC) patients were obtained from The Cancer Genome Atlas (TCGA). We identified 43 differentially expressed necroptosis-related genes (NRGs) in CESC by examining differential gene expression between CESC tumors and normal tissues, and 159 NRGs from the Kyoto Encyclopedia of Genes and Genomes (KEGG) database. Gene ontology (GO) and KEGG enrichment analysis illustrated that the genes identified were mainly related to cell necrosis, extrinsic apoptosis, Influenza A, I − kappaB kinase/NF − kappaB, NOD − like receptor, and other signaling pathways. Subsequently, least absolute shrinkage and selection operator (LASSO) regression and univariate and multivariate Cox regression analyses were used to screen for NRGs that were correlated with patient prognosis. A prognostic signature that includes CAMK2A, CYBB, IL1A, IL1B, SLC25A5, and TICAM2 was established. Based on the prognostic model, patients were stratified into either the high-risk or low-risk subgroups with distinct survival. Receiver operating characteristic (ROC) curve analysis was used to identify the predictive accuracy of the model. In relation to different clinical variables, stratification analyses were performed to demonstrate the associations between the expression levels of the six identified NRGs and the clinical variables in CESC. Immunohistochemical (IHC) validation experiments explored abnormal expressions of these six NRGs in CESC. We also explored the relationship between risk score of this necroptosis signature and expression levels of some driver genes in TCGA CESC database and Gene Expression Omnibus (GEO) datasets. Significant relationships between the six prognostic NRGs and immune-cell infiltration, chemokines, tumor mutation burden (TMB), microsatellite instability (MSI), and immune checkpoints in CESC were discovered. In conclusion, we successfully constructed and validated a novel NRG signature for predicting the prognosis of CC patients and might also play a crucial role in the progression and immune microenvironment in CC.

KIF14 affects cell cycle arrest and cell viability in cervical cancer by regulating the p27Kip1 pathway

Abstract Background Cervical cancer is a kind of malignant gynecological tumor. The first choice for treating cervical cancer is still a combination of surgery and chemoradiotherapy, but the 5-year survival rate remains poor. Therefore, researchers are trying to find new ways to diagnose and treat cervical cancer early. Methods The expression level of KIF14 in cells and tissues was determined via qRT–PCR. The ability of the cells to proliferate, migrate, and invade was examined using CCK-8 assay kits, colony formation assays, and Transwell chambers. The expression levels of Cyclin D1, Cyclin B1, p21, and p27 were also detected using western blot assays. Results The results suggested that p27 is a key regulatory factor in the KIF14-mediated regulation of the cell cycle. In addition, KIF14 knockdown promotes malignancy in cervical cancer cells by inhibiting p27 degradation, resulting in cell cycle arrest. Conclusions KIF14 is an oncogene in cervical cancer, and knocking down KIF14 causes cell cycle arrest by inhibiting p27 degradation, thus affecting cell viability, proliferation, and migration. These results provide a potential therapeutic target for cervical cancer.

Clinical, pathological characteristics, and therapeutic outcomes of primary ovarian carcinoid tumors: a case series of 15 cases

Abstract Background The exact characteristics of primary ovarian carcinoid tumors remain largely unknown because of the rarity of the cases. This study aimed to investigate the clinical features, pathological characteristics, and therapeutic outcomes of patients with primary ovarian carcinoid tumors. Methods This retrospective case series included patients with primary ovarian carcinoid tumors diagnosed between January 2009 and December 2023 at the First Affiliated Hospital of Wenzhou Medical University. Results Fifteen patients were included. They were 45.8 ± 2.7 years at diagnosis. Eight tumors were located in the left ovary, while seven were in the right. All patients were stage I. Microscopically, nine tumors were classified as strumal carcinoid, two as insular carcinoid, three as trabecular carcinoid, and one as mixed. Synaptophysin (Syn) was positive in 14 cases, chromogranin A (CgA) in 10, CD56 in eight, thyroid transcription factor 1 (TTF-1) in five, and thyroglobulin (TG) in six. Twelve patients had a Ki67 index ≤ 7%. All 15 patients underwent surgery, with eight retaining fertility. Among them, one patient underwent comprehensive staging surgery, four underwent lateral adnexectomy, and three underwent cyst stripping. Seven patients underwent total hysterectomy and bilateral adnexectomy, including two patients undergoing comprehensive staging surgery. Three patients received intravenous chemotherapy. One patient was lost to follow-up. The remaining patients were followed up for 48–148 months; they were without recurrences and alive at the last follow-up. Conclusions Primary ovarian carcinoid tumors present with atypical symptoms and signs. Surgical intervention may be an optimal choice for treatment, leading to favorable prognostic outcomes.

Predictive value of 18F-FDG-PET/CT for pathologic complete response (pCR) of lesions after neoadjuvant chemotherapy in advanced ovarian cancer

This study aimed to evaluate the ability of 18F-FDG-PET/CT to predict pathological complete response (pCR) in lesions of patients with advanced epithelial ovarian cancer (EOC) following neoadjuvant chemotherapy (NACT). We assessed whether 18F-FDG-PET/CT could predict lesion-specific pCR prior to interval debulking surgery (IDS), thus guiding precise lesion resection. Twenty-four patients with advanced EOC underwent IDS after NACT. 18F-FDG-PET/CT imaging was performed before and after NACT, with the maximum standardized uptake value (SUVmax) recorded for each metabolically active site. The relationship between the relative change in SUVmax (ΔSUVmax) of grossly visible or suspicious lesions resected during IDS and their pCR status was analyzed. Additionally, the association between omental ΔSUVmax and the chemotherapy response score (CRS) and CA125 elimination rate constant K (KELIM) score was examined. Tumor lesion ΔSUVmax Post-NACT was significantly associated with pCR (P  60.2% predicted pCR in lesions (sensitivity 75.6%, specificity 79.2%), with an area under the curve (AUC) of 0.817 (95% CI: 0.756-0.877, P  59.6% in peritoneal implants (sensitivity 71.4%, specificity 95.7%, AUC 0.905, 95% CI: 0.821-0.989, P  63.95% in metastatic lymph nodes (sensitivity 72.7%, specificity 94.4%, AUC 0.904, 95% CI: 0.815-0.994, P  73.9% in primary lesions (sensitivity 100%, specificity 78.9%, AUC 0.816, 95% CI: 0.642-0.990, P = 0.151) predicted a trend toward significance in pCR results. Omental ΔSUVmax differed significantly between CRS1/2 and CRS3 groups (t = 3.404,P = 0.003); a reduction > 49.95% predicted CRS3 (sensitivity 83.3%, specificity 78.6%, AUC 0.893, 95% CI: 0.736-1.000, P < 0.05). Omental ΔSUVmax was positively correlated with the KELIM score (r = 0.712, P < 0.001), and primary lesion ΔSUVmax was also significant associated with KELIM score (r = 0.547, P = 0.015). 18F-FDG-PET/CT can predict lesion-specific pCR after NACT in advanced EOC, providing guidance for the extent of IDS.

The long-term outcomes of radioactive iodine therapy in malignant struma ovarii with extensive abdominopelvic metastases: a case report and literature review

Struma ovarii (SO) is a rare type of teratoma characterized predominantly by thyroid tissue, accounting for only 1% of all ovarian tumors and 2% of ovarian teratomas. Clinical presentation commonly includes abdominal pain or irregular menstrual cycles. While typically benign, SO may rarely undergo malignant transformation, occurring in an estimated 0.3% to 5.0% of cases. Most cases of malignant struma ovarii (MSO) are diagnosed postoperatively through histopathological examination or incidentally detected during abdominal ultrasound or computed tomography scans. Although MSO exhibits biological behavior analogous to thyroid carcinomas, considerable controversy persists regarding optimal surgical extent and postoperative management, reflecting its unpredictable clinical course, metastatic potential, and relatively high recurrence rate. We report the case of a 40-year-old female patient with MSO accompanied by extensive abdominopelvic metastasis. The patient underwent multiple surgeries, including tumor cytoreduction and total thyroidectomy, followed by radioactive iodine therapy (RAI). At five years of follow-up, she remained disease-free. This case is supplemented by a review of relevant literature on the diagnosis, management, and prognosis of MSO, with the aim of informing clinical decision-making for this rare condition. MSO presents with nonspecific symptoms that complicate preoperative diagnosis. Although current evidence questions the need for aggressive treatment in cases without extraovarian extension, we implemented a primary thyroid carcinoma protocol-including total thyroidectomy and radioactive iodine therapy-to minimize recurrence risk.

Inhibition of HOXC11 by artesunate induces ferroptosis and suppresses ovarian cancer progression through transcriptional regulation of the PROM2/PI3K/AKT pathway

Ferroptosis, a non-apoptotic form of regulated cell death, plays a critical role in the suppression of various tumor types, including ovarian cancer. Artesunate (ART), a derivative of artemisinin, exhibits extensive antitumor effects and is associated with ferroptosis. This study aimed to investigate the mechanisms through which ART induces ferroptosis to inhibit ovarian cancer. RNA sequencing was conducted to identify differentially expressed genes associated with ART-induced ferroptosis. Dual-luciferase reporter assays and electrophoretic mobility shift assays were performed to confirm the interaction between Homeobox C11 (HOXC11) and the Prominin 2 (PROM2) promoter. Cell Counting Kit-8 (CCK-8) assays, flow cytometry, and wound healing assays were used to analyze the antitumor effects of ART. Western blot, biochemical assays and transmission electron microscope were utilized to further characterize ART-induced ferroptosis. In vivo, the effects of ART on ferroptosis were examined using a xenograft mouse model. RNA sequencing analysis revealed that the HOXC11, PROM2 and Phosphatidylinositol 3-Kinase/ Protein Kinase B (PI3K/AKT) pathways were downregulated by ART. HOXC11 was found to regulate PROM2 expression by binding to its promoter directly. HOXC11 overexpression reversed ART-induced effects on ovarian cancer cell proliferation, migration, apoptosis and ferroptosis by activating the PROM2/PI3K/AKT signaling axis. Conversely, silencing PROM2 in HOXC11-overexpressing cells restored ART-induced ferroptosis and its associated antitumor effects by inhibiting the PI3K/AKT pathway. Consistently, in vivo studies using a xenograft mouse model confirmed that ART-induced tumor inhibition was mediated by ferroptosis through the suppression of the HOXC11/PROM2/PI3K/AKT pathway. This study identifies the HOXC11/PROM2/PI3K/AKT axis as a novel regulatory mechanism underlying ART-induced ferroptosis in ovarian cancer. Targeting the HOXC11/PROM2 axis may represent a promising therapeutic strategy for enhancing ferroptosis, offering new insights for the treatment of ovarian cancer.

Hepatic resection for ovarian cancer in Germany: a nationwide epidemiological study based on DRG (diagnosis-related groups) data (2020–2024)

Abstract Background Hepatic metastases from epithelial ovarian cancer (EOC) represent an advanced disease stage, yet national guidelines provide no standardized recommendations for liver resection. This study aimed to describe the national trends and patterns of hepatic resections in EOC patients based on German hospital billing data (DRG system) from 2020 to 2024. Methods A retrospective epidemiological analysis was conducted using InEK (Institute for Hospital Remuneration Systems) datasets from 2020 to 2024. We extracted data related to diagnosis ICD code C56 (malignant neoplasm of the ovary) and OPS codes for hepatic resections (5-501.0, 5-502.0, 5-502.2, 5-502.3, 5-502.4, 5-502.5, 5-502.6). Case numbers, procedure frequency, hospital characteristics, and DRG classifications were analyzed. Results A total of 1,273 hepatic resections were performed in patients with ovarian cancer between 2020 and 2024. Annual case numbers ranged from 225 to 283, indicating stable surgical practice over time. Local excisions / atypical resections accounted for the majority (n = 1,165; 91%), while segmentectomies (n = 85; 6.7%) and major resections (n = 23; 1.8%) were less frequent but consistently performed. Age group analysis showed that the largest proportion of patients undergoing hepatic resection were aged 65–74 years (range 23%–27% yearly). followed by the 60–64 and 55–59 age groups. Younger patients (&lt; 40 years) represented less than 5%. Most procedures (54.6%) were conducted in public hospitals with ≥ 1000 beds, with additional contributions from private non-profit (20.9%) and private for-profit (10.5%) institutions. A gradual increase in the share of private institutions was observed over time. The mean hospital stay varied by resection type: 16.7 days for local excisions, 17.1 days for segmentectomies, and 20.1 days for major resections. Conclusion Hepatic resection for ovarian cancer is performed regularly in Germany, primarily at high-volume centers, suggesting a growing clinical acceptance of aggressive cytoreduction strategies despite the absence of formal recommendations. Our findings underline the need for prospective, multicenter studies and guideline updates addressing hepatic metastases in ovarian cancer.

Real-world risk factors for incomplete cytoreduction in peritoneal carcinomatosis patients scheduled for cytoreductive surgery and hyperthermic intraperitoneal chemotherapy

Cytoreductive surgery with multimodal therapies in advanced or metastatic ovarian, colorectal, and gastric cancers: a systematic review and meta-analysis of randomized trials

Abstract Background Emerging evidence supports cytoreductive surgery (CRS) combined with hyperthermic intraperitoneal chemotherapy (HIPEC) for advanced ovarian cancer, yet its efficacy in other malignancies, such as gastric and colorectal cancers, remains uncertain. This meta-analysis evaluates survival outcomes in patients with advanced or metastatic ovarian, colorectal, and gastric cancers treated with CRS and multimodal therapies (e.g., HIPEC, extensive intraoperative peritoneal lavage (EIPL), systemic chemotherapy, immunotherapy, targeted therapy) versus CRS alone or with control-based regimens, focusing on the applicability of these treatments to these specific cancers. Methods We systematically searched PubMed, EMBASE, Web of Science, the Cochrane Library, and the abstracts of the European Society of Medical Oncology (ESMO) and American Society of Clinical Oncology (ASCO) congresses up to April 21, 2025, for randomized trials published in English. The primary outcomes were overall survival (OS) and progression-free survival (PFS); secondary outcomes included mortality, adverse events, and 3- and 5-year OS rates. Hazard ratios (HRs) and 95% confidence intervals (CIs) were pooled using fixed- or random-effects models, depending on heterogeneity (I²). Findings From 16,064 records, 13 studies (n = 3,925 patients, control group = 1,894, experimental group = 2,031) met inclusion criteria. The experimental group significantly improved OS (HR: 0.86, 95% CI: 0.77 – 0.95, P = 0.003, I² = 22%, P = 0.26) and PFS (HR: 0.67, 95% CI: 0.50 – 0.90, P = 0.009, I² = 83%, P &lt; 0.001) compared to the control group. Subgroup analyses highlighted heterogeneity in PFS benefits, with recent trials (published in or after 2023) showing more potent effects (HR: 0.53, 95% CI: 0.44 – 0.64, P &lt; 0.001). Mortality reduction favored the experimental group (risk ratio (RR): 0.86, 95% CI: 0.75 – 0.99, P = 0.03, I² = 26%, P = 0.24), though clinical relevance requires cautious interpretation. The experimental group significantly increased grade 3 or worse adverse events (RR: 1.31, 95% CI: 1.16 – 1.48, P &lt; 0.001, I² = 31%, P = 0.04), with significant effects driven by digestive system (RR: 1.43, 95% CI: 1.06 – 1.93) and circulatory system (RR: 1.58, 95% CI: 1.07 – 2.32) events. Interpretation CRS combined with multimodal therapies, confers significant survival benefits in advanced ovarian, colorectal, and gastric cancers despite elevated complication risks. These findings support the tailored integration of multimodal strategies in selected patients, highlighting the need for robust randomized trials to validate long-term efficacy and safety.

Is the tail of the pancreas always tumor-infiltrated when macroscopically affected during cytoreductive surgery? A clinicopathological study and experience from a high-volume center

Abstract Background Distal pancreatic resection during cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) is rare, with limited knowledge available. Therefore, a retrospective observational study was conducted using the data registry of a single institution to identify patients that underwent distal pancreatic resection during CRS + HIPEC. Methods All resected pancreatic specimens were examined for invasive parenchymal tumor infiltration. Pre-, peri-, and postoperative variables and their associations were analyzed. Results Over a period of more than a decade, 31 of 1275 patients (2.43%) underwent distal pancreatic resection as part of CRS. Infiltration of the pancreatic parenchyma was confirmed in almost one-third (29.03%) of the cases. Postoperative pancreatic fistulas occurred in 25.81% of patients (87.5% Grade B; 12.5% Grade C). The need for distal pancreatic resection was closely related to tumor burden in the left upper abdomen, with 87% of patients requiring peritonectomy of the left upper abdomen in addition to visceral resection. Pancreatic infiltration (n = 9/31) was diagnosed in 3 cases of gastric carcinoma, 2 cases of colorectal carcinoma, 2 cases of primary peritoneal carcinoma, 1 case of ovarian carcinoma, and 1 case of mucinous appendiceal carcinoma. Postoperative pancreatic fistulas were more frequently associated with primary tumors of the large intestine (87.50% vs. 30.43%; P = 0.0094), and a tendentiously longer total hospital stay was required for the “with pancreatic fistula” group (32.50 ± 19.93 days vs. 21.78 ± 10.14 days), with no impact on patient survival. Conclusions Accepting a slightly increased morbidity, distal pancreatic resection is a reasonable approach to achieve complete macroscopic tumor resection. Nonetheless, our study shows that apparent tumor invasion is histologically rare in cases with favorable tumor biology, such as low-grade pseudomyxoma peritonei. Therefore, pancreatic resection should be avoided in cases of mucinous tumors to prevent fistula formation.

Colonic endometriosis: from subtotal bowel obstruction to malignant transformation - a case series and literature review

Abstract Background Colonic involvement due to endometriosis is a rare condition with a nonspecific clinical presentation. In rare instances, it may undergo malignant transformation, mimicking primary colorectal carcinoma and complicating clinical decision-making. Case presentation We present two cases illustrating the diverse clinical manifestations of colonic endometriosis. In Case 1, a female patient underwent appendectomy for abdominal pain, but further evaluation revealed full-thickness endometriosis of the sigmoid colon, causing subtotal occlusion. In Case 2, sigmoid endometriosis was discovered during endoscopic evaluation prompted by positive occult fecal blood testing. Histopathological analysis revealed malignant transformation to endometrioid adenocarcinoma. In both cases, definitive treatment was achieved via laparoscopic sigmoid resection, highlighting the role of laparoscopic surgery in managing such conditions. Conclusions The potential for malignant transformation of colonic endometriosis and its tendency to mimic colorectal carcinoma underscore the importance of proper tissue sampling methods and histopathological confirmation. A high index of suspicion and appropriate surgical intervention are key to effective management.

Factors associated with declining cytoreductive surgery in advanced epithelial ovarian cancer: a population-based study

Cytoreductive surgery serves as a cornerstone intervention for advanced epithelial ovarian cancer (EOC), yet some patients decline the procedure despite clinical recommendations. This study aimed to evaluate survival outcomes and identify sociodemographic and clinical factors associated with this decision in advanced EOC patients. A retrospective analysis of EOC cases from the Surveillance, Epidemiology, and End Results (SEER) database (2004-2021) was conducted, including patients with stage III/IV EOC recommended for surgery. Patients were categorized into surgical and non-surgical cohorts. Propensity Score Matching (PSM) was applied to adjust for baseline differences, and survival outcomes were compared using Kaplan-Meier and Cox proportional hazards models. Logistic regression analysis was performed to identify predictors of surgery declination. Of the 21,988 patients included, 363 (1.7%) were in the non-surgery group. Following a median follow-up of 33 months, patients in the non-surgical cohort demonstrated significantly lower overall survival (OS) compared to the surgical cohort, with mean OS of 17.8 months versus 45.8 months, respectively (P < 0.001). The Cox model showed increased mortality risk for the non-surgical group post-PSM (HR, 1.87; 95% CI, 1.62-2.15). Non-Hispanic Black, older age, lower household income, nonmetropolitan residence, and unmarried status were associated with higher odds of surgery refusal. Declining surgery is associated with significantly poorer survival in advanced EOC. Sociodemographic factors play a key role in surgical decision-making, underscoring the need for targeted interventions to improve access to surgical care and reduce disparities in EOC treatment outcomes. Further studies should explore the impact of specific chemotherapy and comorbidities on surgery refusal and survival.

Risk factors for postoperative acute kidney injury after cytoreductive surgery combined with hyperthermic intraperitoneal chemotherapy: a meta-analysis and systematic review

Primary extraskeletal osteosarcoma of rectal mesentery: a rare case and literature review

Mapping the landscape of ovarian metastases of gastric cancer: insights, trends, and emerging perspectives

Gastric cancer (GC) has poor prognosis due to distant metastasis with ovarian metastasis (OM) occurring in 5-10% of female patients and survival limited to 7-14 months. No standard treatment exists. This review analyzes global research and trends in OM management. Publications on OM in GC (1991-2024) were retrieved from the Web of Science Core Collection. Bibliometric analysis of 324 articles was performed using CiteSpace and VOSviewer. Three main themes emerged: (1) diagnosis and pathology characteristics of OM, (2) treatment and management, and (3) clinical features in special populations, such as pregnancy. Research hotspots include multidisciplinary treatment (MDT), diagnostic tumor markers (e.g., CA125, CA19-9, and carcinoembryonic antigen (CEA)), imaging (e.g., MRI, ultrasound), and novel approaches such as immunotherapy and targeted therapy (Microsatellite Instability-High (MSI - H), Tumor Mutational Burden-High (TMB - H). Future directions call for multicenter clinical trials and interdisciplinary collaboration to improve patient outcomes.

Integrated molecular subtyping and functional analysis of circ_0001946/miR-7-5p axis reveals a glucose metabolism-linked regulatory mechanism in ovarian cancer

Ovarian cancer (OvCa) remains one of the most lethal gynecological malignancies, primarily due to late-stage diagnosis, chemoresistance, and substantial molecular heterogeneity. Emerging evidence highlights the pivotal roles of microRNAs (miRNAs) and circular RNAs (circRNAs) in tumor progression. Among them, miR-7-5p has been implicated in tumor suppression and the regulation of metabolic pathways. However, its functional interaction with circ_0001946 in OvCa has yet to be elucidated. This study aimed to investigate the interplay between miR-7-5p and circ_0001946 in OvCa, with a particular focus on their regulatory roles in apoptosis, proliferation, tumorigenesis, and glucose metabolism. Using integrated bioinformatics analyses of TCGA and GEO datasets, we identified glucose metabolism-related molecular subtypes. Functional enrichment, immune landscape profiling, and LASSO regression were employed to validate these subtypes and develop prognostic risk models. A series of in vitro and in vivo experiments-including qPCR, CCK-8 assay, flow cytometry, colony formation, dual-luciferase reporter assay, and xenograft tumor models in nude mice-were conducted to evaluate the expression and functional effects of miR-7-5p and circ_0001946. Two molecular subtypes, Subtype-A and Subtype-B, with distinct glucose metabolism and immune profiles were identified. Subtype-A correlated with advanced-stage disease and chemoresistance, while Subtype-B exhibited better prognosis, higher immune infiltration, and activation of metabolic pathways. Circ_0001946 was upregulated in OvCa tissues and cell lines and acted as an oncogene by sponging miR-7-5p. Functional assays revealed that downregulation of miR-7-5p or overexpression of circ_0001946 promoted cell proliferation, inhibited apoptosis, and accelerated tumor growth. Dual-luciferase reporter assays confirmed a direct interaction between miR-7-5p and circ_0001946. Clinical tissue analysis further showed elevated miR-7-5p expression in para-cancerous tissues. The circ_0001946/miR-7-5p regulatory axis contributes to OvCa progression by suppressing apoptosis and promoting cellular proliferation. Targeting this axis presents a promising therapeutic avenue. Additionally, molecular subtyping based on glucose metabolism-related genes offers valuable prognostic information and supports the advancement of personalized treatment strategies in OvCa.

Application of fluorescent tracers in ovarian cancer surgical navigation: a systematic review and meta-analysis

Ovarian cancer is a lethal gynecological health issue, that poses a serious threat to women's health worldwide. The objective of this study was to provide a literature overview of the application of fluorescent tracers during surgical ovarian cancer treatment. We systematically searched 7 electronic databases from inception to September 2024. Studies were included if they investigated the application of fluorescence-guided surgery in patients with a diagnosis of ovarian cancer. Statistical analysis was performed with Stata 14.0 software, and the pooled detection rate and measures of diagnostic accuracy were evaluated. Subgroup analyses were carried out to evaluate the types of tracers, doses, injection sites, etc. Complications and adverse events were also reported. The Quality Assessment of Diagnostic Accuracy Studies 2 tool was used for quality assessment. A total of 21 studies with 681 participants were included. The overall sentinel lymph node (SLN) detection rate was 86.2% (95% CI: 69.6-97.5%; p = 0.000; I Fluorescence-guided surgery is a potentially safe and applicable technique in ovarian cancer surgery. However, considering the small number of participants and the heterogeneity, further studies are needed to better evaluate the accuracy outcomes regarding the type of tracer, dose, injection site, etc.

ctDNA methylation profiling reveals NBL1 as a promising biomarker for early ovarian cancer screening

Early detection of epithelial ovarian cancer (EOC) is crucial for improving patient survival. Current screening methods have limitations, highlighting the need for novel biomarkers. Circulating tumor DNA (ctDNA) methylation analysis offers a promising approach. This study included 10 patients with EOC and 10 patients with benign pelvic masses. We collected plasma samples from these patients and isolated ctDNA. We then conducted whole-genome methylation sequencing using the TAPS (TET-assisted pyridine borane sequencing) method, which allows for single-base resolution detection of 5-methylcytosine and 5-hydroxymethylcytosine. Bioinformatics analysis was performed to identify differentially methylated genes and regions. We further validated candidate biomarkers using bisulfite sequencing, qRT-PCR, and IHC. TCGA methylation data were analyzed for external validation. We identified 35 differentially methylated genes, with NBL1 and CASZ1 as potential candidates. NBL1 gene hypermethylation in EOC patients was significantly associated with reduced mRNA expression, suggesting its role as a tumor suppressor gene. CASZ1 methylation patterns were inconsistent between blood and tissue, indicating limited utility as a diagnostic biomarker. We also observed widespread hypo-methylation across the genome and hyper-methylation in specific regions of differential methylation. GO and KEGG pathway enrichment analyses revealed that the differentially methylated genes were involved in various biological processes and pathways relevant to cancer pathogenesis. There is a significant negative correlation between the methylation level and the mRNA level of the NBL1 gene, suggesting that hypermethylation of the NBL1 gene may be associated with a reduction in its expression. Furthermore, immunohistochemical analysis indicates a downregulation of NBL1 expression in ovarian cancer tissues, which contrasts with the strong positive expression observed in benign tissues. Our study demonstrates the potential of ctDNA methylation analysis for early EOC detection. we propose that NBL1 gene hold potential as screening biomarkers for ovarian cancer.

Comparative effectiveness and safety of treatment regimens for recurrent advanced ovarian cancer: a systematic review and network meta-analysis

The choice of treatment options for recurrent advanced ovarian cancer is very important. However, the most effective treatment options remain unclear. We searched the PubMed, Web of Science, and Cochrane Library databases and the proceedings of the last 5 years of several meetings on ovarian cancer according to the inclusion and exclusion criteria. Randomized controlled trials (RCTs) of recurrent treatment for advanced ovarian cancer with progression-free survival (PFS) were reticulated network meta-analyzed. RCTs were also analyzed for Grades 3 or higher drug-associated adverse events. We included 24 RCTs involving 6,250 patients with advanced recurrent ovarian cancer and a total of 10 treatment regimens. Our network meta-analysis revealed that the PARP plus anti-angiogenic regimen (Surface Under the Cumulative Ranking Curve, SUCRA 95.26%) outperformed eight other regimens and demonstrated a significant improvement in patient survival. The double immunotherapy plus chemotherapy regimen (SUCRA: 87.24%) showed strong efficacy. Additionally, the anti-angiogenic plus chemotherapy regimens (SUCRA: 60.14%), single anti-angiogenic regimens (SUCRA: 52.3%), and poly ADP-ribose polymerase regimens (SUCRA: 61.82%) demonstrated similar efficacy. Interestingly, immunotherapy plus chemotherapy regimens (SUCRA: 31.61%) showed a significant improvement compared to chemotherapy regimens, and double immunotherapy regimens (SUCRA: 36.49%) also demonstrated strong efficacy. However, single immunotherapy regimens (SUCRA: 8.53%) demonstrated limited efficacy. Finally, we found that the incidence of grade 3 or higher adverse reactions was low and manageable for all treatment options. This meta-analysis showed that the PARP plus anti-angiogenic regimen is superior to the other nine regimens in treating patients with advanced recurrent ovarian cancer and can significantly improve their survival. Our results show that the anti-angiogenic plus CT, single-agent anti-angiogenic, and single-agent PARP regimens have similar efficacies; therefore, clinical treatment plans can be adjusted based on the differences in side effects among the three regimens. The double immunotherapy regimen demonstrated superior efficacy compared to the single immunotherapy regimen, particularly in terms of patient survival. These results may offer new therapeutic options for patients with advanced recurrent ovarian cancer, particularly through the use of immunotherapy. PROSPERO (ID CRD420251007476) https://www.crd.york.ac.uk/PROSPERO/view/CRD420251007476 .

Clinicopathological and prognostic factor analyses of primary fallopian tube carcinoma and high-grade serous ovarian cancer: a single-institution retrospective study

This study aimed to evaluate and compare the clinicopathologic features of primary fallopian tubal carcinoma (PFTC) and high-grade serous ovarian cancer (HGSOC) and explore the prognostic factors of these two malignant tumors. Fifty-seven patients diagnosed with PFTC from 2006 to 2015 and 60 patients diagnosed with HGSOC from 2014 to 2015 with complete prognostic information were identified at Women's Hospital of Zhejiang University. The clinicopathological and surgical data were collected, and the survival of the patients was followed for 5 years after surgery. The Cox proportional risk model was used to analyze the impact on survival. For PFTC patients, the mean age was 57 years (range, 35-77 years). The most common clinical manifestations were abnormal vaginal bleeding and/or discharge (61%). A total of 72% of the cases were found at the early stage, and 90% of the tumors were high grade (51 cases). 51% of patients were diagnosed with PFTC before surgery, while the rest were misdiagnosed. Twenty-one patients relapsed. The overall survival (OS) rate was 82%. OS was significantly related to FIGO stage, the preoperative serum CA 125 level, lymphadenectomy, residual tumor size, appendectomy, and the number of cycles of chemotherapy. However, only FIGO stage was an independent prognostic variable for OS. For patients with HGSOC, the OS rate was 67%. OS was significantly related to FIGO stage, residual tumor size, and laterality. However, only residual tumor size was an independent prognostic variable for OS. Our study provides important clinicopathologic insights into PFTC and HGSOC. We identified FIGO stage as an independent prognostic factor for PFTC patients and residual tumor size as an independent prognostic factor for HGSOC patients. These findings emphasize the critical role of accurate staging and achieving a residual tumor size of less than 1 cm during surgery. Our research contributes to refining clinical decision-making, supporting the importance of optimal surgical outcomes, and guiding personalized treatment strategies to improve patient prognosis in both PFTC and HGSOC patients.

Surgery for patients with endometrioid-type endometrial cancer: is lymphadenectomy above the inferior mesenteric artery necessary?

The primary objective of this study was to identify the risk of metastasis to lymph nodes above the inferior mesenteric artery (IMA) in endometrioid-type endometrial cancer (EC) and the factors that influence metastasis. The study included patients who had been operated on for endometrioid-type EC in three gynecological oncology centers between 2007 and 2023. The supramesenteric lymph node (SM-LN) is the region between the left renal vein and the IMA, whereas the inframesenteric lymph node (IM-LN) is the region between the IMA and the aortic bifurcation, as determined by the level of the IMA. The study sample comprised 412 patients. The median number of lymph nodes excised per patient was 58. The median count was 37 for pelvic lymph nodes, 21 for para-aortic lymph nodes, 8 for IM-LN, and 13 for SM-LN. In the univariate analysis, the factors that were found to be statistically significant in determining SM-LN metastasis included tumor size, depth of myometrial invasion, uterine serosal invasion, lymphovascular space invasion (LVSI), cervical invasion, peritoneal cytology, adnexal metastasis, omental metastasis, non-nodal extrauterine metastasis, pelvic lymph node metastasis, and IM-LN metastasis. In the multivariate analysis, SM-LN metastasis was independently associated with tumor size, LVSI, pelvic lymph node metastasis, and IM-LN metastasis. In conclusion, in cases of intermediate-high risk EC, it is important to know that the disease spreads to SM-LN in 7.3% of patients. The efficacy of postoperative adjuvant treatment may be inadequate due to a lack of information regarding the SM-LN region.

Early oral feeding is safe and useful after rectosigmoid resection with anastomosis during cytoreductive surgery for primary ovarian cancer

Abstract Background The aim of this study was to investigate the safety and clinical usefulness of early oral feeding (EOF) after rectosigmoid resection with anastomosis for the treatment of primary ovarian cancer. Methods We performed a retrospective review of all consecutive patients who had undergone rectosigmoid resection with anastomosis for primary ovarian, tubal, or peritoneal cancer between April 2012 and March 2019 in a single institution. Patient-related, disease-related, and surgery-related data including the incidence of anastomotic leakage and postoperative hospital stay were collected. EOF was introduced as a postoperative oral feeding protocol in September 2016. Before the introduction of EOF, conventional oral feeding (COF) had been used. Results Two hundred and one patients who underwent rectosigmoid resection with anastomosis, comprised of 95 patients in the COF group and 106 patients in the EOF group, were included in this study. The median number of postoperative days until the start of diet intake was 5 (range 2–8) in the COF group and 2 (range 2–8) in the EOF group ( P &lt; 0.001). Postoperative morbidity was equivalent between the groups. The incidence of anastomotic leakage was similar (1%) in both groups. The median length of the postoperative hospital stay was reduced by 6 days for the EOF group: 17 (range 9–67) days for the COF group versus 11 (8–49) days for the EOF group ( P &lt; 0.001). Conclusion EOF provides a significant reduction in the length of the postoperative hospital stay without an increased complication risk after rectosigmoid resection with anastomosis as a part of cytoreductive surgery for primary ovarian cancer.

The disease sites of female genital cancers of BRCA1/2-associated hereditary breast and ovarian cancer: a retrospective study

AbstractDisease sites of female genital tract cancers of BRCA1/2-associated hereditary breast and ovarian cancer (HBOC) are less understood than non-hereditary cancers. We aimed to elucidate the disease site distribution of genital cancers in women with the germline BRCA1 and BRCA2 pathogenic variants (BRCA1+ and BRCA2+) of HBOC. For the primary disease site, the proportion of fallopian tube and peritoneal cancer was significantly higher in BRCA2+ (40.5%) compared with BRCA1+ (15.4%) and BRCA− (no pathogenic variant, 12.8%). For the metastatic site, the proportion of peritoneal dissemination was significantly higher in BRCA1+ (71.9%) than BRCA− (55.1%) and not different from BRCA2+ (71.4%). With one of the most extensive patients, this study supported the previous reports showing that the pathogenic variants of BRCA1/2 were involved in the female genitalia’s disease sites.

Decision-making in postoperative chemotherapy for ovarian metastasis from colorectal cancer: a retrospective single-center study

Abstract Background Ovarian metastases from colorectal cancer are relatively uncommon, and no consensus has been reached regarding resection of metastases or chemotherapy before and after surgery. We evaluated the clinicopathological characteristics of ovarian metastases from colorectal cancer and the impact of metastatic resection. We also performed a comparative analysis to clarify the prognostic impact of metastatic resection and the choice of chemotherapy before and after surgery. Methods Between 2006 and 2014, 38 patients at our institution underwent resection of ovarian metastases from colorectal cancer. Clinicopathological data were extracted from the patients’ records and evaluated with respect to the long-term outcome. For 15 patients with metachronous ovarian metastases who received chemotherapy until immediately before resection, we compared the prognosis with and without changes in the regimen after resection. Results The 5-year overall survival rate was 19.9%, and the median survival duration was 27.2 months. The survival rate in the R0 resection group (n = 8) was significantly better than that in the R1/2 resection group (n = 30) (P = 0.0004). Patients without peritoneal dissemination (n = 15) or extra-ovarian metastases (n = 31) had a significantly better prognosis than those with peritoneal dissemination (n = 23) or extra-ovarian metastases (n = 7) (P = 0.040 and P = 0.0005, respectively). The progression-free survival and median survival times of patients who resumed chemotherapy after resection without a change in their preoperative regimen were 10.2 months and 26.2 months, respectively, while those among patients with a change in their regimen before resection versus after resection were 11.0 months and 18.1 months, respectively. The difference between the two groups was not statistically significant (progression-free survival time and median survival time: P = 0.52 and P = 0.48, respectively). Conclusions Patients who underwent R0 resection of ovarian metastases clearly had a better prognosis than those who underwent R1/2 resection. Additionally, a poor prognosis was associated with the presence of peritoneal dissemination and extra-ovarian metastases. The data also suggested that resumption of chemotherapy without changing the regimen after resection could preserve the next line of chemotherapy for future treatment and improve the prognosis.

Rare occurrence of pseudomyxoma peritonei (PMP) syndrome arising from a malignant transformed ovarian primary mature cystic teratoma treated by cytoreductive surgery and HIPEC: a case report

Abstract Background Pseudomyxoma peritonei (PMP) syndrome is a disease process that typically occurs from ruptured appendiceal mucocele neoplasms. PMP syndrome arising from malignant transformation of an ovarian primary mature cystic teratoma (MCT) is a pathogenesis rarely encountered. Case Presentation Herein, we report a 28-year-old patient evaluated and treated for a right ovarian mass and large volume symptomatic abdominopelvic mucinous ascites. Molecular profiling and genetic analysis revealed mutations in ATM, GNAS, and KRAS proteins while IHC demonstrated gastrointestinal-specific staining for CK20, CDX2, CK7, and SATB2. Peritoneal cytology showed paucicellular mucin. Diffuse peritoneal adenomucinosis (DPAM) variant of PMP arising from a ruptured ovarian primary MCT after malignant transformation to a low-grade appendiceal-like mucinous neoplasm was ultimately confirmed. Treatment included staged therapeutic tumor debulking and right salpingo-oophorectomy followed by cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (HIPEC). Conclusions Our report builds upon the existing literature supporting this aggressive treatment option reserved for advanced abdominal malignancies utilized in this patient with a rare clinical entity.

Analysis of long-term outcomes in 44 patients following pelvic exenteration due to cervical cancer

Abstract Background Pelvic exenteration (PE) may be associated with prolonged overall survival (OS) in selected patients with advanced or recurrent cervical cancer. However, the factors related to improved survival following PE are not clearly defined. The aim of this study was to perform a retrospective analysis of OS rates in a group of patients undergoing PE in order to identify the factors related to improved long-term outcomes. Methods Our study group consisted of 44 patients, including 21 squamous cell cancer (SCC) patients, 22 patients with adenocarcinomas (AC) of the cervix, and one patient with undifferentiated cervical carcinoma. The patients were categorized according to the type of surgery, namely, primary surgery (12 patients) or surgery due to cancer recurrence (32 patients). Results In the group of patients with recurrent cervical cancer, we found that improved OS correlated with the SCC histological type and the presence of vaginal fistula. The need for reoperation within 30 days and the presence of severe adverse events significantly worsened the prognosis. We found a non significant trend toward improved survival in those patients with tumor-free margins. Lymph node metastases, the initial stage of the disease, the time to recurrence, and a history of hysterectomy had no impact on patients’ OS. In the group of patients undergoing primary PE, we observed a trend toward improved survival among those diagnosed with vaginal fistula. Conclusions Pelvic exenteration seemed to improve the long-term outcomes for patients with SCC cancer recurrence and vaginal fistula whose surgery was unrelated to severe adverse events.

Potential risks in sentinel lymph node biopsy for cervical cancer: a single-institution pilot study

Abstract Background Sentinel lymph node (SLN) biopsy is an attractive technique that is widely performed in many oncological surgeries. However, the potential risks in SLN biopsy for cervical cancer remains largely unclear. Methods Seventy-five patients with histologically confirmed cervical cancer were enrolled between May 2014 and June 2016. SLN biopsies were performed followed by pelvic lymphadenectomies and all resected nodes were labeled according to their anatomic areas. Only bilateral detections of SLNs were considered successful. Patients’ clinicopathologic feature, performance of SLN detection, and distributions of lymph node metastases were analyzed. Results Of the 75 enrolled patients, at least one SLN was detected in 69 (92.0%), including 33 in bilateral and 36 in unilateral. SLNs were most detected in the obturator area (52 of 69 patients, 75.4%) and 26 (37.7%) patients presented SLNs in more than one area of hemipelvis. Lymphovascular invasion was found to be the only factor that adversely influenced SLN detection, while the tumor diameter, growth type, histological grade, deep stromal invasion, and neoadjuvant chemotherapy showed no significant impacts. Patients with lymphovascular invasion showed a significantly higher rate to have unsuccessful detection (90.9% versus 41.5%, P &lt; 0.001) and lymph node metastasis (40.9% versus 3.8%, P &lt; 0.001) compared with those without. Nodal metastases were confirmed in 11 patients, of whom 9 (81.8%) had lymphovascular invasion and 7 (63.6%) had non-SLN metastasis. The most frequently involved SLNs were obturator nodes (9/11, 81.8%). In addition, the parametrial nodes also have a high rate to be positive (4/11, 36.4%), although they were relatively less identified as SLNs. Besides, 3 patients showed metastases in the laterals without SLN detected. Conclusions In cervical cancer, lymphovascular invasion is a significant factor for unsuccessful SLN detection. The risk of having undetected metastasis is high when SLN is positive; therefore, further lymphadenectomy may be necessary for these patients.

Patterns of care for vulvar cancer and insights from revised FIGO staging: a retrospective study

The objective of this study was to evaluate the clinicopathological characteristics and patterns of care among women diagnosed with vulvar malignancy at a tertiary care teaching institute. Additionally, the study aimed to analyse the implications of revised FIGO staging system on stage shift and patient outcomes. A retrospective observational study was conducted, wherein hospital records of biopsy-proven cases of vulvar cancers managed over a period of 10 years were comprehensively reviewed. The assignment of FIGO staging was performed utilizing both 2009 and 2021 FIGO staging systems for comparative analysis. Statistical analysis was performed using STATA version 17. Survival curves were constructed using the Kaplan-Meier method, with differences assessed using the log-rank test. Additionally, multivariable analysis was conducted using the Cox proportional hazard model. A total of 82 cases meeting the inclusion criteria were enrolled in the study. Management patterns varied widely, with the majority undergoing surgery (73.2%), followed by definitive radiotherapy with or without chemotherapy (10.9%), neoadjuvant radiotherapy and subsequent surgery (4.9%), and palliative care (10.9%). Post-operative radiotherapy was administered in 31.7% of cases. The disease-specific recurrence rate was found to be 32.9%, and the mortality rate was 30.5%. The median Disease-Free Survival (DFS) was 17 months (interquartile range [IQR]: 1-36 months), while the Overall Survival (OS) was 27 months (IQR: 9-52 months). Upon application of the 2021 staging system, a stage shift was observed in 18% of cases of advanced vulvar cancer. The 3-year DFS and OS were reduced for stage IIIA and stage IVA, while showing improvement for stage IIIB. The revised FIGO 2021 staging system offers enhanced simplicity in its application within clinical practice and demonstrates improved correlation with prognosis. Approximately 18% cases experienced restaging under the updated system. Not applicable.

Chemical composition of surgical smoke produced during the loop electrosurgical excision procedure when treating cervical intraepithelial neoplasia

Abstract Background As LEEP (loop electrosurgical excision procedure) is being increasingly used for the diagnosis and treatment of uterine cervical intraepithelial neoplasia, surgical smoke during LEEP has become an inevitable health issue. Therefore, in this study, exposure to the chemical substances in surgical smoke produced during LEEP was assessed. Methods Smoke samples from patients with high-grade cervical intraepithelial neoplasia undergoing LEEP were collected by smoke-absorbing devices situated 1 m away from the operating table and near the nose of the operator during LEEP. Each plume sample was collected after 5 patients underwent LEEP, requiring 5 min for smoke collection for each patient. The chemicals of exposure to surgical smoke were assessed, and the hazard classes of these chemical components were evaluated by the International Agency for Research on Cancer. Results Qualitative analysis of the smoke produced during LEEP revealed a variety of potentially toxic chemicals under standard detection, such as benzene, toluene, xylene, ethylbenzene, styrene, butyl acetate, acrylonitrile, 1,2-dichloroethane, phenol, chlorine, cyanide, hydrogen cyanide and carbon monoxide. Additionally, the average concentration of carbon dioxide was 0.098 ± 0.015% during surgery and was higher than that before surgery (0.072 ± 0.007%, P &lt; 0.001), and the concentration of formaldehyde was significantly higher during surgery (0.023 ± 0.009 mg/m3, P &lt; 0.05) than before surgery (0.012 ± 0.001 mg/m3, P &lt; 0.05). Conclusions Most of the detected chemical concentrations in smoke generated during LEEP were below the exposure limits when local exhaust ventilation procedures were efficiently used. However, the concentrations of carbon dioxide and formaldehyde found in smoke were significantly higher after surgery. Wearing a high-filtration mask and using evacuation devices routinely and consistently when performing LEEP are recommended to protect perioperative personnel.

Clinical value of MRI, serum SCCA, and CA125 levels in the diagnosis of lymph node metastasis and para-uterine infiltration in cervical cancer

Abstract Background Cervical cancer shows great differences in depth of invasion, metastasis, and other biological behaviors. The location of the lesion is special, so it is usually difficult to determine the clinical stage. This study aimed to explore the clinical value of magnetic resonance imaging (MRI) and tumor serum markers for the preoperative diagnosis of cervical cancer lymph node metastasis and para-uterine invasion. Methods A total of 200 patients with cervical cancer admitted to our hospital from January 2019 to January 2020 were collected as the research subjects. Comparing the diagnosis results of preoperative MRI scan, serum tumor markers, and postoperative pathological examination using single factor comparison, we determined the MRI scan results, the comprehensive matching rate between serum tumor markers (squamous cell carcinoma antigen (SCCA), carbohydrate antigen 125 (CA125)) and postoperative pathological results, and the differences of sensitivity, specificity, and accuracy in the prediction of lymph node metastasis and para-uterine infiltration of cervical cancer. Results The levels of SCCA and CA125 in patients with para-uterine invasion and lymph node metastasis were higher than those of patients without invasion and metastasis. Among them, the level of SCCA was significantly different (P&lt;0.05). The level of CA125 was not statistically significant (P&gt;0.05), so MRI combined with serum SCCA was selected for combined diagnosis in the later period. The sensitivity, specificity, and accuracy of MRI diagnosis of cervical cancer and para-uterine infiltrating lymph node metastasis and metastasis were 55.2, 91.6, and 89.5% and 55.2, 91.6, and 89.5%, respectively. These data in MRI combined with serum SCCA were 76.3, 95.3, and 94.3% and 63.2, 96.0, and 95.1%, respectively. The accuracy of tumor markers combined with MRI in the diagnosis of cervical cancer lymph node metastasis and para-uterine invasion was higher than that of MRI. Conclusions MRI combined with serum SCCA can more accurately identify cervical cancer lymph node metastasis and para-uterine invasion compared with MRI alone. Tumor marker combined with MRI diagnosis is an important auxiliary method for cervical cancer treatment and can provide comprehensive and reliable clinical evidence for evaluation before cervical cancer surgery.

Inflammatory myofibroblastic tumour of an unusual presentation in the uterine cervix: a case report

Abstract Background Inflammatory myofibroblastic tumour is an infrequent mesenchymal neoplasia of unknown aetiology and variable behaviour, ranging from rather benign lesions to locally aggressive and even metastatic disease. Its presence has been described in almost all organs; however, its location in the female genital tract has rarely been reported. Case presentation We present the case of a 47-year-old female, who was studied in our institution for a recent medical history of several weeks of dyspareunia and abdominal pain. She underwent pertinent studies including ultrasonography and CT scan. Under suspicion of degenerated leiomyoma, a total hysterectomy was performed. Unexpectedly, the pathological study of the surgical specimen showed very few tumour cells with focal fusiform morphology surrounded by an abundant inflammatory infiltrate; a thorough immunohistochemistry study lead to myofibroblastic tumour of the cervix diagnosis. A PET-CT scan did not show metastatic disease. The patient did not undergo any adjuvant treatment, and she is currently on surveillance with no evidence of disease relapse. Conclusions Inflammatory myofibroblastic tumour remains a rare entity yet to be fully elucidated. The diagnosis is based on pathological study due to the lack of typical clinical manifestations and typical radiological images. Surgical resection is the most frequent treatment, whereas chemotherapy and radiotherapy are restricted to locally advanced or metastatic disease. Tirosine kinase inhibitor crizotinib has shown promising results especially in tumours harbouring ALK mutation.

Determination of a six-gene prognostic model for cervical cancer based on WGCNA combined with LASSO and Cox-PH analysis

Abstract Aim This study aimed to establish a risk model of hub genes to evaluate the prognosis of patients with cervical cancer. Methods Based on TCGA and GTEx databases, the differentially expressed genes (DEGs) were screened and then analyzed using GO and KEGG analyses. The weighted gene co-expression network (WGCNA) was then used to perform modular analysis of DEGs. Univariate Cox regression analysis combined with LASSO and Cox-pH was used to select the prognostic genes. Then, multivariate Cox regression analysis was used to screen the hub genes. The risk model was established based on hub genes and evaluated by risk curve, survival state, Kaplan-Meier curve, and receiver operating characteristic (ROC) curve. Results We screened 1265 DEGs between cervical cancer and normal samples, of which 620 were downregulated and 645 were upregulated. GO and KEGG analyses revealed that most of the upregulated genes were related to the metastasis of cancer cells, while the downregulated genes mostly acted on the cell cycle. Then, WGCNA mined six modules (red, blue, green, brown, yellow, and gray), and the brown module with the most DEGs and related to multiple cancers was selected for the follow-up study. Eight genes were identified by univariate Cox regression analysis combined with the LASSO Cox-pH model. Then, six hub genes (SLC25A5, ENO1, ANLN, RIBC2, PTTG1, and MCM5) were screened by multivariate Cox regression analysis, and SLC25A5, ANLN, RIBC2, and PTTG1 could be used as independent prognostic factors. Finally, we determined that the risk model established by the six hub genes was effective and stable. Conclusions This study supplies the prognostic value of the risk model and the new promising targets for the cervical cancer treatment, and their biological functions need to be further explored.

Long non-coding RNA XIST regulates ovarian cancer progression via modulating miR-335/BCL2L2 axis

Abstract Background X inactivation-specific transcript (XIST) is the long non-coding RNA (lncRNA) related to cancer, which is involved in the development and progression of various types of tumor. However, up to now, the exact role and molecular mechanism of XIST in the progression of ovarian cancer are not clear. We studied the function of XIST in ovarian cancer cells and clinical tumor specimens. Methods RT-qPCR was performed to detect the expression levels of miR-335 and BCL2L2 in ovarian cancer cells and tissues. MTT and transwell assays were carried out to detect cell proliferation, migration, and invasion abilities. Western blot was performed to analyze the expression level of BCL2L2. The interaction between miR-335 and XIST/BCL2L2 was confirmed using a luciferase reporter assay. Results The inhibition of XIST can inhibit the proliferation invasion and migration of human ovarian cancer cells. In addition, the miR-335/BCL2L2 axis was involved in the functions of XIST in ovarian cancer cells. These results suggested that XIST could regulate tumor proliferation and invasion and migration via modulating miR-335/BCL2L2. Conclusion XIST might be a carcinogenic lncRNA in ovarian cancer by regulating miR-335, and it can serve as a therapeutic target in human ovarian cancer.

MiR-186-3p attenuates tumorigenesis of cervical cancer by targeting IGF1

Abstract Background Mounting evidence in the cancer literature suggests that microRNAs (miRNAs) influence the progression of human cancer cells by targeting protein-coding genes. How insulin-like growth factor 1(IGF1) and miR-186-3p contribute to the development of cervical cancer (CC) remains unclear. This study examined the regulatory roles of miR-186-3p and IGF1 in CC development. Methods Gene expression levels were determined by qRT-PCR. Proliferation, migration, and apoptosis of CC and normal cells were determined by MTT, Transwell, and caspase-3 activity assays, respectively. Dual-luciferase reporter activity and RNA pull-down assays were performed to identify the target gene of miR-186-3p. Results IGF1 was the target of miR-186-3p. The expression of miR-186-3p inhibited cell proliferation and migration abilities of CC cell lines, but induced the apoptosis rate of CC cells. IGF1 could restore the inhibitory effects of miR-186-3p on the proliferation, migration, and apoptosis abilities of CC cells. Experimental results revealed that miR-186-3p could inhibit IGF1 expression, thereby reducing the viability of CC cells. Conclusions The data suggest that targeting of IGF1 by miR-186-3p could be crucial in regulating the progression of CC.

‘En bloc’ peritoneal mesometrial resection (PMMR) and pelvic targeted compartmental lymphadenectomy (TCL) for management of patients with endometrial cancer – feasibility and safety study of a ‘new kid on the block’ in robotic surgery

Robotic Peritoneal Mesometrial Resection and Targeted Compartmental Lymphadenectomy (PMMR + TCL) is a procedure following Cancer Field Surgery concept for endometrial cancer (EC), enabling superior locoregional control without adjuvant irradiation. We aimed to test the feasibility and safety of performing the PMMR + TCL by a newly trained team in a robotic approach. A single-institution, retrospective analysis of patients undergoing robotic surgery (DaVinci) for EC was performed. The PMMR + TCL was compared to a robotic simple hysterectomy (rSH) and sentinel lymph node dissection (SLND). The primary outcomes were the rate of PMMR + TCL among all robotic surgeries and the 30-day complications (Clavien-Dindo classification). The PMMR + TCL was performed on 79 (66.9%), rSH + SLND with afferent lymphatic vessels on 17 (14.4%), rSH + SLND alone on 20 (16.9%), and radical hysterectomy with SLND/lymphadenectomy on 2 (1.6%) patients, with the median number (range) of removed lymph nodes of 8 (2-12), 6 (2-10), 6 (1-7), and 26 (4-26), respectively. Patients in whom the PMMR + TCL was performed were younger, had lower BMI, and fewer co-morbidities as compared to those who underwent other procedures. Thirteen (11%) patients experienced complications, with 3 (2.5%) grade IIIb, of which none could be directly linked to any type of procedure. Ten (8.5%) patients experienced postoperative grade I-II complications, which tended to be more frequent after PMMT + TCL. Endometriosis and carcinoma deposits were found between uterus and lymph nodes in 7 (8.8%) of PMMR + TCL specimens. Performing PMMT + TCL by a team newly trained in robotic surgery was feasible and relatively safe. Further research on locoregional control after PMMR + TLC without adjuvant irradiation should be conducted.

Neoadjuvant chemotherapy followed by radical surgery reduces radiation therapy in patients with stage IB2 to IIA2 cervical cancer

Abstract Background To investigate whether carboplatin-liposomal paclitaxel neoadjuvant chemotherapy (NACT) benefits patients with locally advanced cervical cancer (LACC) through avoiding or delaying postoperative radiation. Methods A total of 414 patients with cervical cancer of International Federation of Gynecology and Obstetrics (FIGO 2009) stages IB2–IIA2 were included in the retrospective cohort study, who had received carboplatin-liposomal paclitaxel chemotherapy followed by radical surgery (NACT group) or primary radical surgery (PRS group) between 2007 and 2017 at our hospital. The baseline clinicopathological characteristics at diagnosis, postoperative pathological risk factors, and oncological outcomes after surgery, including postoperative radiation (as adjuvant treatment or treatment of recurrent diseases), progression-free survival (PFS), and overall survival (OS), were compared between the groups. Before treatment, the patients in the NACT group had significantly more advanced tumor stages and larger tumor sizes than those in the PRS group. Results The NACT reduced the tumor volumes remarkedly with a response rate of 62.4%, and the tumors in the NACT group were smaller than those in the PRS group when the patients were subjected to radical surgery. Furthermore, postoperative pathology examination revealed less frequent deep stromal invasion in the NACT group than in the PRS group. According to the presence of pathological risk factors for recurrence, 54.82% of women in the NACT group needed adjuvant radiotherapy, while 60.87% in the PRS group, and in fact, 33.00% of NACT patients and 40.09% of PRS patients received adjuvant radiation. In addition, 8.12% of NACT patients and 9.68% of PRS patients underwent radiotherapy after relapse. The cumulative postoperative radiation rate was significantly lower in the NACT group (P = 0.041), while the differences in 5-year OS and PFS were not statistically significant between the groups. Conclusions NACT reduces the pathological risk factors and the use of radiation without compromising survival in patients with LACC, which may protect younger patients from radiation-related side effects and subsequently improve the quality of life. Trial registration ISRCTN Registry, ISRCTN24104022

Metastatic gastric adenocarcinoma to the uterine cervix—a case report and review of the literature

Abstract Background Poorly differentiated diffuse-type gastric adenocarcinoma often presents at an advanced stage. While gastric cancer typically metastasizes to the liver, lung and bone, metastasis to the uterine cervix is extremely rare. To our knowledge, less than forty cases have been described in the medical literature. Case presentation We report a case of a 47-year-old woman who presented to us with symptomatic uterine leiomyomas and subsequently underwent a successful total laparoscopic hysterectomy and bilateral salpingo-oophorectomy. The diagnosis of metastatic cancer involving the cervix was established incidentally on histopathology, which demonstrated atypical signet ring cells in the lymphovascular spaces of the cervix. Further investigations for a primary malignancy revealed a poorly differentiated diffuse-type gastric adenocarcinoma. Conclusion Gastric cancer involving the uterine cervix is rare and associated with a poor prognosis. When presented with isolated cervical metastases, the gastrointestinal tract should be considered as a possible primary source. Due to the limited publications on this clinical entity, we expect to raise awareness and study this unique manifestation of gastric cancer by presenting our case.

Re-stratification of patients with copy-number low endometrial cancer by clinicopathological characteristics

Abstract Objective To stratify patients with copy-number low (CNL) endometrial cancer (EC) by clinicopathological characteristics. Methods EC patients who underwent surgery between June 2018 and June 2022 at Peking University People’s Hospital were included and further classified according to TCGA molecular subtyping: POLE ultramutated, microsatellite instability high (MSI-H), CNL, and copy-number high (CNH). Clinicopathological characteristics and prognosis of CNL patients were retrospectively reviewed. The Cox proportional hazards regression model was applied to perform univariate and multivariate analysis, and independent risk factors were identified. Differentially expressed genes (DEGs) according to overall survival (OS) were screened based on the transcriptome of CNL cases from the TCGA program. Finally, a nomogram was established, with an accuracy analysis performed. Results (1) A total of 279 EC patients were included, of whom 168 (60.2%) were in the CNL group. A total of 21 patients had recurrence and 6 patients deceased, and no significant difference in recurrence-free survival (RFS) was exhibited among the four molecular subtypes (P = 0.104), but that in overall survival (OS) was statistically significant (P = 0.036). (2) CNL patients were divided into recurrence and non-recurrence groups, and significant differences (P &lt; 0.05) were found between the two groups in terms of pathological subtype, FIGO stage, ER, PR, glycated hemoglobin (HbA1c), and high-density lipoprotein cholesterol (HDL-C). All the above factors were included in univariate and multivariate Cox regression models, among which pathological subtype, PR, and HDL-C were statistically different (P &lt; 0.05), resulting in three independent risk factors for the prognosis of patients in the CNL group. (3) By comparing the transcriptome of tumor tissues between living and deceased CNL patients from the TCGA database, 903 (4.4%) DEGs were screened, with four lipid metabolism pathways significantly enriched. Finally, a nomogram was established, and internal cross-validation was performed, showing good discrimination accuracy with an AUC of 0.831 and a C-index of 0.748 (95% CI 0.444–1.052). (4) According to the established nomogram and the median total score (85.89), patients were divided into the high score group (n = 85) and low score group (n = 83), and the 8 patients with recurrence were all in the high score group. Survival analysis was performed between the two groups, and the difference in RFS was statistically significant (P = 0.010). Conclusion In the CNL group of EC patients, pathological subtype, PR, and HDL-C were independent prognostic risk factors, the nomogram established based upon which had a good predictive ability for the recurrence risk of patients with CNL EC.