The role of neoadjuvant chemotherapy before radical surgery in stage IB2/IIA2 squamous cell cervical cancers.

BACKGROUND: This study aimed to evaluate the outcomes of patients diagnosed with stage IB2/IIA2 cervical squamous cell carcinoma who underwent neoadjuvant chemotherapy (NACT) prior to radical hysterectomy compared to those who did not receive NACT before surgery. MATERIALS AND METHODS: This is a multicenter study including data of 6 gynecological oncology departments. The study is approved from one of the institution's local ethics committee. Patients were stratified into two cohorts based on the receipt of NACT preceding their surgical intervention. Clinico-pathological factors and progression-free survival were analyzed. RESULTS: Totally 87 patients were included. Lymphovascular space invasion (LVSI) was observed as 40% in the group receiving NACT, while it was 66.1% in the group not receiving NACT (p = 0.036). Deep stromal invasion (> 50%) was 56% in the group receiving NACT and 84.8% in the group not receiving NACT (p = 0.001). In the univariate analysis, application of NACT is statistically significant among the factors that would be associated with disease-free survival. Consequently, a multivariate analysis was conducted for progression-free survival, incorporating factors such as the depth of stromal invasion, the presence of LVSI, and the administration of NACT. Of these, only the administration of NACT emerged as an independent predictor associated with decreased progression-free survival. (RR:5.88; 95% CI: 1.63-21.25; p = 0.07). CONCLUSIONS: NACT shouldn't be used routinely in patients with stage IB2/IIA2 cervical cancer before radical surgery. Presented as oral presentation at National Congress of Gynaecological Oncology & National Congress of Cervical Pathologies and Colposcopy (2022/ TURKEY).

Does HPV-18 co-infection increase the risk of cervical pathology in individuals with HPV-16?

OBJECTIVE: We aimed to investigate differences between HPV-16 mono- and HPV-16/18 co-infections in terms of cervical dysplasia and invasive cancer. METHODS: This multicentre, retrospective study spanned from December 2017 to December 2020, involving women who visited gynaecological oncology clinics for colposcopy with either HPV-16 or HPV-16/18 positivity. A total of 736 patients, 670 in Group 1 (HPV-16 positivity) and 66 in Group 2 (HPV-16/18 positivity), were compared for the presence of CIN2+ lesions detected by colposcopic biopsy or endocervical curettage (ECC). Exclusions included hysterectomized patients, those with prior gynaecological cancers, and patients with HPV positivity other than types 16 and 18. RESULTS: Among the included patients, 42.4% had a diagnosis of CIN2+ lesions. The cytology results demonstrated abnormal findings in 45.3% in Group 1 and 42.2% in Group 2, with no significant difference between the groups. ECC revealed CIN2+ lesion in 49 (8.7%) patients in group 1, while only 1 (1.7%) patient had CIN2+ lesion in group 2. There was no difference between 2 groups in terms of ECC result (p = 0.052). In group 1, 289 (43.1%) patients had CIN2+ lesion, while 23 (34.8%) patients had CIN2+ lesions in group 2. There was no difference between group 1 and 2 in terms of diagnosis of CIN2+ lesions (p = 0.19). CONCLUSION: This multicentre retrospective study found no significant differences between HPV-16 mono- and HPV-16/18 co-infections regarding cervical pathologies. Larger studies are needed to validate and further explore these findings.

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

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

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

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

Clinicopathological features of atypical glandular cells, not otherwise specified, on cervicovaginal pap smears.

OBJECTIVE: The Papanicolaou (Pap) smear test is a standard screening test that detects cervical lesions and cancers. In this multicentric study, we performed a retrospective analysis of cytological results associated with atypical glandular cells, not otherwise specified (AGC-NOS). METHODS: We retrospectively reviewed Pap smear tests that resulted as AGC-NOS. A total of 254 women who underwent colposcopy due to a Pap smear result of AGC-NOS were included the study between 2003 and 2021. The ages, Pap smear results, HPV results if any, colposcopic biopsy results, endocervical and endometrial pathology results, and management of these patients were analysed. RESULTS: Two hundred fifty-four patients with AGC-NOS Pap smear results were included in the study. A total of 70 (27.6%) patients had cervical and endometrial premalignant or malignant lesions. Malignancy was observed in 17 (6.7%) patients (endometrium, n = 11 [4.3%]; cervix, n = 6 [2.4%]). Isolated premalignant or malignant lesions of the cervix and endometrium were detected in 57 (22.4%) and 12 (4.7%) patients, respectively. CONCLUSIONS: Patients diagnosed with AGC-NOS should undergo a careful evaluation with all clinicopathological features. Because cancer of the cervix and endometrium is not rare in patients diagnosed with AGC-NOS, colposcopic examination with endocervical sampling should be a priority based on a cervicovaginal smear. Endometrial sampling is also required according to the patient's clinic, age, and examination characteristics.

Neoadjuvant chemotherapy in patients with stage IVB uterine serous carcinoma: a Turkish multicentric study.

The aim of this study was to evaluate the prognostic factors for and determine the effect of neoadjuvant chemotherapy (NACT) on oncologic outcome in stage IVB pure serous endometrial carcinoma patients who received taxane and platinum. Forty-two patients with 2009 International Federation of Gynecology and Obstetrics (FIGO) stage IVB uterine serous carcinoma were enrolled from six gynecologic oncology centers and a study group was created. The study group had a 2-year disease-free survival (DFS) of 32% and 2-year disease-specific survival (DSS) of 73%. On univariate analysis; lymphadenectomy (not performed vs. performed), paraaortic lymph node metastasis (positive vs. negative) and number of metastatic lymph node count (≤5 vs. >5) were found to have statistical significance for DFS (p < 0.001, p = 0.026 and p = 0.044, respectively). Adnexal metastasis (positive vs. negative) and type of cytoreductive surgery (maximal vs. optimal and suboptimal) had statistical significance for DSS (p = 0.041 and p = 0.015, respectively). Receiving NACT did not affect DFS and DSS in stage IVB uterine serous carcinoma patients. As our sample size was small, precise conclusions could not be made for suggesting the use of NACT in advanced stage uterine serous carcinoma. For more accurate results, more randomized controlled studies are needed in this patient group.IMPACT STATEMENTWhat is already known on this subject? Endometrial carcinoma is the most common type of gynecologic tract malignancies and usually it is diagnosed at early stages. Although the favorable prognosis, uterine serous carcinoma (USC), one of the rarest subtypes, has a poorer prognosis when compared to other histological subtypes. USC has a propensity to spread beyond pelvis. Due to this aggressive behavior, surgical intervention could not be feasible in advanced stage disease.What do the results of this study add? Our study evaluated the prognostic factors that affect survival in advanced stage USC patients. Also we investigated that neoadjuvant chemotherapy (NACT) could improve oncologic outcomes. Performing lymphadenectomy, presence of paraaortic lymph node and adnexal metastasis, number of metastatic lymph nodes and type of cytoreductive surgery improved survival in advanced stage USC patients. However, NACT did not have a statistical significance as a predictor for disease-specific survival (DSS) and disease-free survival (DFS).What are the implications of these findings for clinical practice and/or further research? Maximal surgical effort should be performed in advanced stage USC according to our results. On the other hand, NACT had no impact on DSS and DFS rates. For this reason, we could not be able to suggest the routine use of NACT in advanced stage USC. But more randomized controlled trials are warranted for confirmation of our results.

SUCCOR cone study: conization before radical hysterectomy.

OBJECTIVE: To evaluate disease-free survival of cervical conization prior to radical hysterectomy in patients with stage IB1 cervical cancer (International Federation of Gynecology and Obstetrics (FIGO) 2009). METHODS: A multicenter retrospective observational cohort study was conducted including patients from the Surgery in Cervical Cancer Comparing Different Surgical Aproaches in Stage IB1 Cervical Cancer (SUCCOR) database with FIGO 2009 IB1 cervical carcinoma treated with radical hysterectomy between January 1, 2013, and December 31, 2014. We used propensity score matching to minimize the potential allocation biases arising from the retrospective design. Patients who underwent conization but were similar for other measured characteristics were matched 1:1 to patients from the non-cone group using a caliper width ≤0.2 standard deviations of the logit odds of the estimated propensity score. RESULTS: We obtained a weighted cohort of 374 patients (187 patients with prior conization and 187 non-conization patients). We found a 65% reduction in the risk of relapse for patients who had cervical conization prior to radical hysterectomy (hazard ratio (HR) 0.35, 95% confidence interval (CI) 0.16 to 0.75, p=0.007) and a 75% reduction in the risk of death for the same sample (HR 0.25, 95% CI 0.07 to 0.90, p=0.033). In addition, patients who underwent minimally invasive surgery without prior conization had a 5.63 times higher chance of relapse compared with those who had an open approach and previous conization (HR 5.63, 95% CI 1.64 to 19.3, p=0.006). Patients who underwent minimally invasive surgery with prior conization and those who underwent open surgery without prior conization showed no differences in relapse rates compared with those who underwent open surgery with prior cone biopsy (reference) (HR 1.94, 95% CI 0.49 to 7.76, p=0.349 and HR 2.94, 95% CI 0.80 to 10.86, p=0.106 respectively). CONCLUSIONS: In this retrospective study, patients undergoing cervical conization before radical hysterectomy had a significantly lower risk of relapse and death.

SUCCOR quality: validation of ESGO quality indicators for surgical treatment of cervical cancer.

OBJECTIVE: To evaluate whether compliance with European Society of Gynaecological Oncology (ESGO) surgery quality indicators impacts disease-free survival in patients undergoing radical hysterectomy for cervical cancer. METHODS: In this retrospective cohort study, 15 ESGO quality indicators were assessed in the SUCCOR database (patients who underwent radical hysterectomy for International Federation of Gynecology and Obstetrics (FIGO) stage 2009 IB1, FIGO 2018 IB1, and IB2 cervical cancer between January 2013 and December 2014), and the final score ranged between 0 and 16 points. Centers with more than 13 points were classified as high-quality indicator compliance centers. We constructed a weighted cohort using inverse probability weighting to adjust for the variables. We compared disease-free survival and overall survival using Cox proportional hazards regression analysis in the weighted cohort. RESULTS: A total of 838 patients were included in the study. The mean number of quality indicators compliance in this cohort was 13.6 (SD 1.45). A total of 479 (57.2%) patients were operated on at high compliance centers and 359 (42.8%) patients at low compliance centers. High compliance centers performed more open surgeries (58.4% vs 36.7%, p<0.01). Women who were operated on at centers with high compliance with quality indicators had a significantly lower risk of relapse (HR=0.39; 95% CI 0.25 to 0.61; p<0.001). The association was reduced, but remained significant, after further adjustment for conization, surgical approach, and use of manipulator surgery (HR=0.48; 95% CI 0.30 to 0.75; p=0.001) and adjustment for adjuvant therapy (HR=0.47; 95% CI 0.30 to 0.74; p=0.001). Risk of death from disease was significantly lower in women operated on at centers with high adherence to quality indicators (HR=0.43; 95% CI 0.19 to 0.97; p=0.041). However, the association was not significant after adjustment for conization, surgical approach, use of manipulator surgery, and adjuvant therapy. CONCLUSIONS: Patients with early cervical cancer who underwent radical hysterectomy in centers with high compliance with ESGO quality indicators had a lower risk of recurrence and death.

Post-recurrence survival analysis of patients with pulmonary recurrence from gynaecologic cancers: a multi-institutional analysis of 122 patients.

In this retrospective study, patients with epithelial gynaecologic cancer with pulmonary recurrence (PR) were evaluated from five national gynaecologic oncology clinics. Patients with a diagnosis of primary endometrial, ovarian/fallopian tube/peritoneal, cervical or vaginal/vulvar tumours who developed an initial PR were included in the study A total of 122 patients were included in the study. The median follow-up time after recurrence was 7.5 (range, 1-84) months. The 2-year PRS was 48% in the main cohort. The risk of death was more than seven times higher in patients who did not receive salvage chemotherapy compared with those who did (hazard ratio: 7.6, 95% CI: 3.0-18.9; p < .001). When squamous cell carcinoma was compared with the other tumour types, the risk of death increased more than three times (hazard ratio: 3.7, 95% CI: 1.4-9.6; p = .007).IMPACT STATEMENTWhat is already known on this subject? Pulmonary recurrence (PR) from gynaecologic malignancies is rare and can cause major clinical problem. Therefore, defining the clinical and pathologic characteristics and recurrence patterns are essential.What the results of this study add? This study demonstrates non-squamous subtype and salvage chemotherapy at PR were associated with improved survival.What of these findings for clinical practice and/or further research? To the best of our knowledge, our study is the largest study to investigate the clinico-pathologic characteristics, recurrence patterns, treatment options, and post-recurrence survival (PRS) in patients with PR from epithelial gynaecologic cancers. Future research should examine the underlying causes of these findings.

The relationship between spiritual well-being, hope and depression in gynecologic oncology patients.

The authors' aim in this study was to determine the relationship between spiritual well-being, hope and depression in gynecologic oncology patients. This is a descriptive and correlational study. The patients received a total of 41.59 ± 12.11 points from the Spiritual Well-Being Scale, 5.57 ± 4.19 points from the Beck Hopelessness Scale, and 14.92 ± 11.61 points from the Beck Depression Scale. Gynecologic oncology patients had high spiritual well-being levels and low hopelessness and depression levels, and their hopelessness and depression levels decreased and hope levels increased as their spiritual well-being levels increased.

Low-grade endometrial stromal sarcoma: A Turkish uterine sarcoma group study analyzing prognostic factors and disease outcomes.

OBJECTIVE: To investigate factors associated with refractory disease, recurrence, or death as well as disease-free survival (DFS) and overall survival (OS) in low-grade endometrial sarcoma (LGESS). METHODS: A multi-institutional, retrospective study was conducted in a total of 124 patients, who received a curative-intent surgery. The exclusion criteria were as follows: i) history of any other invasive disease; ii) neoadjuvant therapy; iii) fertility sparing surgery; iv) a different diagnosis after review of the slides. RESULTS: All patients underwent hysterectomy, 96% had bilateral salpingo-oophorectomy, and 65% had lymphadenectomy. Twelve (14.8%) of 81 patients undergoing lymphadenectomy had lymph node (LN) metastasis. Of those, 8 (9.8%) had pelvic LN metastasis whereas 4 (5.6%) had isolated paraaortic LN metastasis. Six of 8 (75%) patients with positive pelvic LNs had concurrent paraaortic LN metastasis. Among 124 patients, 3 patients (2.4%) had refractory disease following primary therapy. During a median follow-up of 45.5 months, 27 (22.3%) of 121 patients who achieved complete remission after primary therapy developed recurrence, and 10 patients (8.1%) died of disease. The 3-year DFS and OS were 76.9% and 93.8%, respectively. Stage was the sole independent prognostic factor in the whole cohort. When analyzing factors within subgroups of stage I and stage ≥II, there was no significant prognostic factor for stage I; however, lymphadenectomy and adjuvant chemotherapy were significantly associated with disease outcomes for stage ≥II. While lymphadenectomy was related with improved DFS, chemotherapy was associated with poor DFS and OS. CONCLUSION: The risk of LN metastasis at pelvic as well as paraaortic lymphatic basins is not negligible to omit lymphadenectomy in stage ≥II LGESS. Moreover, lymphadenectomy provides significant DFS advantage in patients with extrauterine disease.

Prophylactic subcutaneous retention sutures in the prevention of superficial wound separation of midline laparotomy.

OBJECTIVES: This prospective study aimed to determine the effectiveness of prophylactic subcutaneous retention sutures in the prevention of superficial wound separation in women with a confirmed or suspected cancer who had gynecological surgery by midline laparotomy. METHODS: This was a non-randomized, controlled intervention study including patients who underwent cancer surgery between May 2018 and August 2019. Patients who underwent midline laparotomy with confirmed or suspected cancer were included and patients who had an early post-operative complication or who underwent surgery again before the removal of stitches were excluded. The independent variables that might predict the superficial wound site dehiscence and prolongation of the hospitalization period were analyzed using logistical regression analysis. RESULTS: A total of 208 patients were included in the study. Age, presence of comorbid diseases, low pre-operative hemoglobin, low pre-operative albumin, higher weight, higher body mass index (BMI), pre- and post-operative blood transfusion, and absence of retention sutures were associated with higher risk of superficial wound separation. Low pre-operative albumin, weight, and BMI were associated with prolonged length of hospital stay. In a multivariate analysis, BMI (OR: 1.12; 95% CI: 1.09 to 1.28, p<0.001) and retention sutures (OR: 0.31; 95% CI: 0.11 to 0.83, p=0.019) retained an independent association with superficial wound separation. In addition, BMI (OR: 1.11; 95% CI: 1.03 to 1.25, p=0.010) and intra-operative complications (OR: 4.10; 95% CI: 1.08 to 15.60, p=0.038) were independent predictors increasing the length of hospital stay, and use of retention sutures (OR: 0.19; 95% CI: 0.05 to 0.66, p=0.009) was an independent predictor decreasing the length of hospital stay. CONCLUSIONS: Prophylactic subcutaneous retention sutures reduced superficial wound separation and shortened hospital stay. Prophylactic subcutaneous retention sutures may be considered in patients who undergo gynecological surgery using a midline laparotomy.

Radical hysterectomy in early cervical cancer in Europe: characteristics, outcomes and evaluation of ESGO quality indicators.

INTRODUCTION: Comprehensive updated information on cervical cancer surgical treatment in Europe is scarce. OBJECTIVE: To evaluate baseline characteristics of women with early cervical cancer and to analyze the outcomes of the ESGO quality indicators after radical hysterectomy in the SUCCOR database. METHODS: The SUCCOR database consisted of 1272 patients who underwent radical hysterectomy for stage IB1 cervical cancer (FIGO 2009) between January 2013 and December 2014. After exclusion criteria, the final sample included 1156 patients. This study first described the clinical, surgical, pathological, and follow-up variables of this population and then analyzed the outcomes (disease-free survival and overall survival) after radical hysterectomy. Surgical-related ESGO quality indicators were assessed and the accomplishment of the stated recommendations was verified. RESULTS: The mean age of the patients was 47.1 years (SD 10.8), with a mean body mass index of 25.4 kg/m2 (SD 4.9). A total of 423 (36.6%) patients had a previous cone biopsy. Tumor size (clinical examination) <2 cm was observed in 667 (57.7%) patients. The most frequent histology type was squamous carcinoma (794 (68.7%) patients), and positive lymph nodes were found in 143 (12.4%) patients. A total of 633 (54.8%) patients were operated by open abdominal surgery. Intra-operative complications occurred in 108 (9.3%) patients, and post-operative complications during the first month occurred in 249 (21.5%) patients, with bladder dysfunction as the most frequent event (119 (10.3%) patients). Clavien-Dindo grade III or higher complication occurred in 56 (4.8%) patients. A total of 510 (44.1%) patients received adjuvant therapy. After a median follow-up of 58 months (range 0-84), the 5-year disease-free survival was 88.3%, and the overall survival was 94.9%. In our population, 10 of the 11 surgical-related quality indicators currently recommended by ESGO were fully fulfilled 5 years before its implementation. CONCLUSIONS: In this European cohort, the rate of adjuvant therapy after radical hysterectomy is higher than for most similar patients reported in the literature. The majority of centers were already following the European recommendations even 5 years prior to the ESGO quality indicator implementations.

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

OBJECTIVE: Prognostic factors associated with high-grade endometrial stromal sarcoma (HGESS) and undifferentiated uterine sarcoma (UUS) have not been distinctly determined due to the repetitive changes in the World Health Organization (WHO) classification. We aimed to compare clinicopathologic features and outcomes of patients with HGESS with those of patients with UUS. METHODS: A multi-institutional, retrospective, cohort study was conducted including 71 patients, who underwent surgery at 13 centers from 2008 to 2017. An experienced gynecopathologist from each institution re-evaluated the slides of their own cases according to the WHO2014 classification. Factors associated with refractory/progressive disease, recurrence or death were examined using logistic regression analyses. Kaplan-Meier method and log-rank test were used for survival comparisons. RESULTS: The median disease-free survival (DFS) for HGESS and UUS was 12 months and 6 months, respectively. While the median overall survival was not reached in HGESS group, it was 22 months in the UUS group. Kaplan-Meier analyses revealed that patients with UUS had a significantly poorer DFS than those with HGESS (p = 0.016), although OS did not differ between the groups (p = 0.135). Lymphovascular-space involvement (LVSI) was the sole significant factor associated with progression, recurrence or death for HGESS (Hazard ratio: 9.353, 95% confidence interval: 2.539-34.457, p = 0.001), whereas no significant independent factor was found for UUS. CONCLUSIONS: UUS has a more aggressive behavior than HGESS. While no significant predictor of prognosis was found for UUS, LVSI is the sole independent prognostic factor for HGESS, with patients 9.3 times more likely to experience refractory/progressive disease, recurrence or death.

SUCCOR study: an international European cohort observational study comparing minimally invasive surgery versus open abdominal radical hysterectomy in patients with stage IB1 cervical cancer.

BACKGROUND: Minimally invasive surgery in cervical cancer has demonstrated in recent publications worse outcomes than open surgery. The primary objective of the SUCCOR study, a European, multicenter, retrospective, observational cohort study was to evaluate disease-free survival in patients with stage IB1 (FIGO 2009) cervical cancer undergoing open vs minimally invasive radical hysterectomy. As a secondary objective, we aimed to investigate the association between protective surgical maneuvers and the risk of relapse. METHODS: We obtained data from 1272 patients that underwent a radical hysterectomy by open or minimally invasive surgery for stage IB1 cervical cancer (FIGO 2009) from January 2013 to December 2014. After applying all the inclusion-exclusion criteria, we used an inverse probability weighting to construct a weighted cohort of 693 patients to compare outcomes (minimally invasive surgery vs open). The first endpoint compared disease-free survival at 4.5 years in both groups. Secondary endpoints compared overall survival among groups and the impact of the use of a uterine manipulator and protective closure of the colpotomy over the tumor in the minimally invasive surgery group. RESULTS: Mean age was 48.3 years (range; 23-83) while the mean BMI was 25.7 kg/m2 (range; 15-49). The risk of recurrence for patients who underwent minimally invasive surgery was twice as high as that in the open surgery group (HR, 2.07; 95% CI, 1.35 to 3.15; P=0.001). Similarly, the risk of death was 2.42-times higher than in the open surgery group (HR, 2.45; 95% CI, 1.30 to 4.60, P=0.005). Patients that underwent minimally invasive surgery using a uterine manipulator had a 2.76-times higher hazard of relapse (HR, 2.76; 95% CI, 1.75 to 4.33; P<0.001) and those without the use of a uterine manipulator had similar disease-free-survival to the open surgery group (HR, 1.58; 95% CI, 0.79 to 3.15; P=0.20). Moreover, patients that underwent minimally invasive surgery with protective vaginal closure had similar rates of relapse to those who underwent open surgery (HR, 0.63; 95% CI, 0.15 to 2.59; P<0.52). CONCLUSIONS: Minimally invasive surgery in cervical cancer increased the risk of relapse and death compared with open surgery. In this study, avoiding the uterine manipulator and using maneuvers to avoid tumor spread at the time of colpotomy in minimally invasive surgery was associated with similar outcomes to open surgery. Further prospective studies are warranted.

A nomogram for decision-making of completion surgery in endometrial cancer diagnosed after hysterectomy.

OBJECTIVE: Extrauterine tumor spread is one of the essential determinants of disease outcome in endometrial cancer. However; more than 30% of patients still undergo incomplete surgery at the initial attempt. Strategies regarding the management of patients with incompletely staged early-stage disease or patients with undebulked advanced-stage disease remain controversial. Depending on postoperative uterine features and findings on imaging, patients may be put on observation or receive adjuvant therapy or undergo re-staging or debulking surgery followed by adjuvant therapy. To identify patients who would most benefit from a completion surgery, either for restaging or for cytoreduction, we developed a nomogram for estimation of extrauterine disease based on findings of final hysterectomy specimen. METHODS: Data of 336 patients whose extrauterine disease status was known were analyzed. A nomogram was constructed using patient characteristics including age, grade, myometrial invasion, lymphovascular space involvement, cervical involvement, and peritoneal cytology. The nomogram was internally validated in terms of discrimination, calibration and overall performance. RESULTS: The nomogram showed good performance accuracy with an area under the receiver operating characteristic curve of 0.870, a specificity of 95.5%, and a positive predictive value of 73.9%. Decision curve analysis revealed that the use of the nomogram in decision-making for completion surgery leads to the equivalent of a net 18 true-positive results per 100 patients without an increase in the number of false-positive results. CONCLUSIONS: Estimation of extrauterine disease from final hysterectomy specimen is possible with high predictive performance using the nomogram developed. The nomogram may help clinicians in decision-making for management of incomplete surgeries.

What is the impact of stromal microinvasion on oncologic outcomes in borderline ovarian tumors? A multicenter case-control study.

PURPOSE: To investigate clinicopathological characteristics and oncological outcome of women with microinvasive BOTs. METHODS: A retrospective multicenter case-control study was conducted on 902 patients with BOT, who underwent surgery from January 2002 to December 2015 at six participating gynecologic oncology centers from Turkey. Among 902 patients, 69 had microinvasive BOT. For every patient with microinvasive BOT, two controls were randomly selected from another database based on decade of age and stage of disease at diagnosis. The clinical-pathological characteristics and oncological outcomes were compared between BOT patients with and without stromal microinvasion. Risk factors for poor oncological outcomes were investigated in a multivariate analysis model. Overall survival (OS) and disease-free survival (DFS) were estimated using the Kaplan-Meier method. RESULTS: Patients with microinvasive BOT had a significantly higher rate of recurrence than patients without microinvasive BOT (17.4 vs 7.8%, OR 3.55, %95 CI 1.091-11.59, p = 0.03). Stage at diagnosis (stage I versus II/III) and type of surgery (cystectomy versus others) were found as other significant prognostic factors for recurrence in multivariate analysis (OR 8.63, %95 CI 2.48-29.9, p = 0.001 and OR 19.4, %95 CI 3.59-105.6, p = 0.001, respectively). Stromal microinvasion was found as a prognostic factor for significantly shorter DFS (26.7 vs 11.9 months, p = 0.031, log rank). However, there was no significant difference in OS between two groups (p = 0.99, log rank). CONCLUSION: Stromal microinvasion is significantly associated with decreased DFS. In addition, our study confirms that the risk of recurrence is higher in patients with microinvasive BOT.

Assessment of circulating betatrophin concentrations in lean glucose-tolerant women with polycystic ovary syndrome.

The aims of the current study were to investigate the betatrophin levels in lean glucose-tolerant women with polycystic ovary syndrome (PCOS), and to explore the relationships between these levels and antropometric, hormonal and metabolic parameters. The study population consisted of 50 lean (body mass index [BMI] < 25 kg/m2) women diagnosed with PCOS using the Rotterdam criteria, and 60 age- and BMI-matched healthy controls without any features of clinical or biochemical hyperandrogenism. Before recruitment, glucose tolerance was evaluated in all of the subjects using the 2-h 75 g oral glucose-tolerance test, and only those exhibiting normal glucose tolerance were enrolled. Serum betatrophin levels were significantly higher in women with PCOS (median 322.3; range 44.7-1989.3 ng/L) compared to the controls (median 199.9; range 6.2-1912.9 ng/L; p = .005). In the control group, no significant correlation was evident between betatrophin levels and clinical or biochemical parameters. In the PCOS group, betatrophin levels were positively correlated with prolactin levels (r = .286, p = .046) and negatively correlated with BMI (r = -.283, p = .049), waist/hip ratio (r = -.324, p = .023), and low-density lipoprotein cholesterol levels (r = -.385, p = .006). Impact statement What is already known on this subject: Several studies have suggested that primary alteration in beta-cell function is a pathophysiological feature of PCOS, and insulin resistance is the most significant predictor of beta-cell dysfunction independent of obesity. Betatrophin is a circulating protein that is primarily expressed in the liver in humans. Early experimental investigations demonstrated that overexpression of betatrophin significantly promoted pancreatic beta-cell proliferation, insulin production and improved glucose tolerance. Few studies have investigated the association between PCOS and betatrophin. However, in contrast to our study, the authors included overweight/obese patients and glucose tolerance was not evaluated before recruitment. What the results of this study add: Our results showed that serum betatrophin levels were significantly higher in lean glucose-tolerant PCOS women than in age- and BMI-matched healthy controls. What are the implications of these findings for clinical practice and/or further research: Elevated betatrophin levels in PCOS women, in the absence of obesity and glucose intolerance, may reflect a compensatory mechanism in order to counteract metabolic syndrome-related risk factors.

Validation of Revised FIGO Staging Classification for Cancer of the Ovary, Fallopian Tube, and Peritoneum Based on a Single Histological Type.

OBJECTIVE: This study aimed to evaluate the prognostic significance of revised International Federation of Gynecology and Obstetrics (FIGO2013) staging classification for cancer of the ovary, fallopian tube, and peritoneum in patients exhibiting high-grade serous histology. METHODS: Clinical records of patients with high-grade serous carcinoma who underwent primary surgery between 2007 and 2012 were reviewed retrospectively. Patients were reclassified according to the FIGO2013 criteria. Progression-free survival (PFS) and overall survival (OS) were calculated for each stage using Kaplan-Meier estimates and compared with the log-rank test. RESULTS: In total, 125 patients were included in the analysis. The distribution of the study cohort according to the revised classification was as follows; stage I, 6 patients; stage II, 9 patients; stage III, 85 patients; and stage IV, 25 patients. Median follow-up time was 36 months (95% confidence interval [CI], 3-110). The median PFS and OS were 14 months (95% CI, 12.4-15.6) and 60 months (95% CI, 47.0-72.9), respectively. Both PFS and OS were significantly different among stages I, II, III, and IV (P < 0.01). Subgroup analyses for stage III disease also revealed significant differences in survival. The median PFS for stages IIIA1, IIIB, and IIIC was 56, 46, and 16 months, respectively (P < 0.01), and the median OS was 104, 95, and 60 months, respectively (P = 0.03). The outcomes of patients with stage IV disease differed slightly but nonsignificantly according to new substages. The median PFS for stages IVA and IVB was 12 and 6 months, respectively (hazard ratio, 1.16; 95% CI, 0.48-2.79; P = 0.72), and the median OS was 41 and 24 months, respectively (hazard ratio, 1.62; 95% CI, 0.58-4.55; P = 0.35). The study sample was insufficient in size for subgroup analyses in stages I and II. CONCLUSIONS: The revised FIGO2013 staging system is highly prognostic for discriminating outcomes of patients with high-grade serous carcinoma across stages I to IV, in subgroups of stage III, but not in subgroups of stage IV.

Analysis of Metastatic Regional Lymph Node Locations and Predictors of Para-aortic Lymph Node Involvement in Endometrial Cancer Patients at Risk for Lymphatic Dissemination.

OBJECTIVE: The aim of this study was to provide detailed knowledge of the metastatic lymph node (LN) locations and to determine factors predicting para-aortic LN metastasis in endometrial cancer patients at risk (intermediate/high) for LN involvement. METHODS: A prospective case series with planned data collection was conducted in a total of 173 patients who treated with systematic pelvic para-aortic lymphadenectomy up to the renal vessels. All the LNs removed from pelvic and para-aortic basins­low or high according to the level of the inferior mesenteric artery­were evaluated separately. Logistic regression analyses were performed to determine the impact of variables on para-aortic metastasis. RESULTS: Lymph node metastasis was observed in 21.9% of the patients, pelvic LN involvement in 17.9%, para-aortic LN involvement in 15.0%, both pelvic and para-aortic LN involvement in 10.9%, and isolated para-aortic LN involvement in 4.0%. The most common metastatic LN locations were the external iliac (50.0%), obturator (50.0%), and low precaval regions (36.8%). The least common location of metastasis was the high precaval region (5.3%). Among patients with para-aortic LN metastasis, 42.3% had metastasis above the inferior mesenteric artery. The number of metastatic pelvic LNs greater than or equal to 2 was the only independent predictor of para-aortic metastasis in multivariate analysis (odds ratio, 23.38; 95% confidence interval, 1.35-403.99; P = 0.030), with 96.94% sensitivity, 95.87% specificity, 98.6% positive predictive value, and 97.0% negative predictive value. CONCLUSIONS: The current study supports the idea that in patients at risk of LN involvement, the systematic lymphadenectomy should be performed up to the renal vessels due to the high rate of upper level involvement.