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.

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.

Diagnostic accuracy of sentinel node biopsy in non-endometrioid, high-grade and/or deep myoinvasive endometrial cancer: A Turkish gynecologic oncology group study (TRSGO-SLN-006).

INTRODUCTION: This study aimed to evaluate the diagnostic accuracy of the sentinel lymph node (SLN) mapping algorithm in high-risk endometrial cancer patients. METHODS: Two hundred forty-four patients with non-endometrioid histology, grade 3 endometrioid tumors and/or tumors with deep myometrial invasion were enrolled in this retrospective, multicentric study. After removal of SLNs, all patients underwent pelvic ± paraaortic lymphadenectomy. Operations were performed via laparotomy, laparoscopy or robotic surgery. Indocyanine green (ICG) and methylene blue (MB) were used as tracers. SLN detection rate, sensitivity, negative predictive value (NPV) and false-negative rate (FNR) were calculated. RESULTS: Surgeries were performed via laparotomy in 132 (54.1%) patients and 152 (62.3%) underwent both bilateral pelvic and paraaortic lymphadenectomy. At least 1 SLN was detected in 222 (91%) patients. Fifty-five (22.5%) patients had lymphatic metastasis and 45 patients had at least 1 metastatic SLN. Lymphatic metastases were detected by side-specific lymphadenectomy in 8 patients and 2 patients had isolated paraaortic metastasis. Overall sensitivity, NPV and FNR of SLN biopsy were 81.8%, 95% and 18.2%, respectively. By applying SLN algorithm steps, sensitivity and NPV improved to 96.4% and 98.9%, respectively. For grade 3 tumors, sensitivity, NPV and FNR of the SLN algorithm were 97.1%, 98.9% and 2.9%. CONCLUSION: SLN algorithm had high diagnostic accuracy in high-risk endometrial cancer. All pelvic metastases were detected by the SLN algorithm and the isolated paraaortic metastasis rate was ignorable. But long-term survival studies are necessary before this approach becomes standard of care.

Can risk groups accurately predict non-sentinel lymph node metastasis in sentinel lymph node-positive endometrial cancer patients? A Turkish Gynecologic Oncology Group Study (TRSGO-SLN-004).

BACKGROUND AND OBJECTIVES: The purpose of this study was to find out the risk factors associated with non-sentinel lymph node metastasis and determine the incidence of non-sentinel lymph node metastasis according to risk groups in sentinel lymph node (SLN)-positive endometrial cancer patients. METHODS: Patients who underwent at least bilateral pelvic lymphadenectomy after SLN mapping were retrospectively analyzed. Patients were categorized into low, intermediate, high-intermediate, and high-risk groups defined by ESMO-ESGO-ESTRO. RESULTS: Out of 395 eligible patients, 42 patients had SLN metastasis and 16 (38.1%) of them also had non-SLN metastasis. Size of SLN metastasis was the only factor associated with non-SLN metastasis (p = .012) as 13/22 patients with macrometastasis, 2/10 with micrometastasis and 1/10 with isolated tumor cells (ITCs) had non-SLN metastasis. Although all 4 metastases (1.8%) among the low-risk group were limited to SLNs, the non-SLN involvement rate in the high-risk group was 42.9% and all of these were seen in patients with macrometastatic SLNs. CONCLUSIONS: Non-SLN metastasis was more frequent in higher-risk groups and the risk of non-SLN metastasis increased with the size of SLN metastasis. Proceeding to complete lymphadenectomy when SLN is metastatic should further be studied as the effect of leaving metastatic non-SLNs in-situ is not known.

Sentinel lymph node biopsy in early stage endometrial cancer: a Turkish gynecologic oncology group study (TRSGO-SLN-001).

OBJECTIVE: The aim of this multicenter study was to evaluate the feasibility of sentinel lymph node (SLN) mapping in clinically uterine confined endometrial cancer. METHODS: Patients who underwent primary surgery for endometrial cancer with an SLN algorithm were reviewed. Indocyanine green or blue dye was used as a tracer. SLNs and/or suspicious lymph nodes were resected. Side specific lymphadenectomy was performed when mapping was unsuccessful. SLNs were ultrastaged on final pathology. RESULTS: 357 eligible patients were analyzed. Median age was 59 years. Median number of resected SLNs was 2 (range 1-12) per patient. Minimal invasive and open surgeries were performed in 264 (73.9%) and 93 (26.1%) patients, respectively. Indocyanine green was used in 231 (64.7%) and blue dye in 126 (35.3%) patients. The dyes were injected into the cervix in 355 (99.4%) patients. The overall and bilateral SLN detection rates were 91.9% and 71.4%, respectively. The mapping rates using indocyanine green or blue dye were comparable (P=0.526). There were 43 (12%) patients with lymphatic metastasis. The SLN algorithm was not able to detect 3 of 43 patients who had isolated paraaortic metastasis. After SLN biopsy, complete pelvic lymphadenectomy was performed in 286 (80.1%) patients. Sensitivity and negative predictive value were both 100% for the detection of pelvic lymph node metastases. In addition, 117 (32.8%) patients underwent completion paraaortic lymphadenectomy after SLN biopsy. In these patients, sensitivity for detecting metastases to pelvic and/or paraaortic lymph nodes was 90.3% with a negative predictive value of 96.6%. The risk of non-SLN involvement in patients with macrometastatic SLNs, micrometastatic SLNs, and isolated tumor cells in SLNs were 61.2%, 14.3% and 0%, respectively. CONCLUSIONS: SLN biopsy had good accuracy in detecting lymphatic metastasis. However, one-third of cases with metastatic SLNs also had non-SLN involvement and this risk increased to two-thirds of cases with macrometastatic SLNs. The effect of leaving these nodes in situ on survival should be evaluated in further studies.

Combination of sentinel lymph node mapping and uterine frozen section examination to reduce side-specific lymphadenectomy rate in endometrial cancer: a Turkish Gynecologic Oncology Group study (TRSGO-SLN-002).

OBJECTIVE: This study aimed to find out whether side-specific pelvic lymphadenectomy can be omitted without compromising diagnostic efficacy according to "reflex frozen section" analysis of the uterus in case of sentinel lymph node (SLN) mapping failure. METHODS: Patients who underwent surgery for endometrial cancer with an SLN algorithm were stratified as low-risk or high-risk according to the uterine features on the final pathology reports. Two models for low-risk patients were defined to omit side-specific pelvic lymphadenectomy: strategy A included patients with endometrioid histology, grade 1-2, and <50% myometrial invasion irrespective of the tumor diameter; strategy B included all factors of strategy A with the addition of tumor diameter ≤2 cm. Theoretical side-specific pelvic lymphadenectomy rates were calculated for the two strategies, assuming side-specific pelvic lymphadenectomy was omitted if low-risk features were present on reflex uterine frozen examination, and compared with the standard National Comprehensive Cancer Network (NCCN) SLN algorithm. RESULTS: 372 endometrial cancer patients were analyzed. 230 patients (61.8%) had endometrioid grade 1 or 2 tumors with <50% myometrial invasion (strategy A), and in 123 (53.4%) of these patients the tumor diameter was ≤2 cm (strategy B); 8 (3.5%) of the 230 cases had lymphatic metastasis. None of them were detected by side-specific pelvic lymphadenectomy and metastases were limited to SLNs in 7 patients. At least one pelvic side was not mapped in 107 (28.8%) cases in the entire cohort, and all of these cases would require a side-specific pelvic lymphadenectomy based on the NCCN SLN algorithm. This rate could have been significantly decreased to 11.8% and 19.4% by applying reflex frozen section examination of the uterus using strategy A and strategy B, respectively. CONCLUSION: Reflex frozen section examination of the uterus can be a feasible option to decide whether side-specific pelvic lymphadenectomy is necessary for all the patients who failed to map with an SLN algorithm. If low-risk factors are found on frozen section examination, side-specific pelvic lymphadenectomy can be omitted without compromising diagnostic efficacy for lymphatic spread.

SATEN III-Splitting Adjuvant Treatment of stage III ENdometrial cancers: an international, multicenter study.

INTRODUCTION: The purposes of this study were to compare adjuvant treatment modalities and to determine prognostic factors in stage III endometrioid endometrial cancer (EC). METHODS: SATEN III was a retrospective study involving 13 centers from 10 countries. Patients who had been operated on between 1998 and 2018 and diagnosed with stage III endometrioid EC were analyzed. RESULTS: A total of 990 women were identified; 317 with stage IIIA, 18 with stage IIIB, and 655 with stage IIIC diseases. The median follow-up was 42 months. The 5-year disease-free survival (DFS) of patients with stage III EC by adjuvant treatment modality was 68.5% for radiotherapy (RT), 54.6% for chemotherapy (CT), and 69.4% for chemoradiation (CRT) (p=0.11). The 5-year overall survival (OS) for those patients was 75.6% for RT, 75% for CT, and 80.7% for CRT (p=0.48). For patients with stage IIIA disease treated by RT versus CT versus CRT, the 5-year OS rates were 75.6%, 75.0%, and 80.7%, respectively (p=0.48). Negative peritoneal cytology (HR: 0.45, 95% CI: 0.23 to 0.86; p=0.02) and performance of lymphadenectomy (HR: 0.33, 95% CI: 0.16 to 0.77, p=0.001) were independent predictors for improved OS for stage IIIA EC. For women with stage IIIC EC treated by RT, CT, and CRT, the 5-year OS rates were 78.9%, 67.0%, and 69.8%, respectively (p=0.08). Independent prognostic factors for better OS for stage IIIC disease were age <60 (HR: 0.50, 95%CI: 0.36 to 0.69, p<0.001), grade 1 or 2 disease (HR: 0.59, 95% CI: 0.37 to 0.94, p=0.014; and HR: 0.65, 95%CI: 0.46 to 0.91, p=0.014, respectively), absence of cervical stromal involvement (HR: 063, 95% CI: 0.46 to 0.86, p=0.004) and performance of para-aortic lymphadenectomy (HR: 0.52, 95% CI: 0.35 to 0.72, p<0.001). DISCUSSION: Although not statistically significant, CRT seemed to be a better adjuvant treatment option for stage IIIA endometrioid EC. Systematic lymphadenectomy seemed to improve survival outcomes in stage III endometrioid EC.

Risk factors for failure of sentinel lymph node mapping using indocyanine green/near-infrared fluorescent imaging in endometrial cancer.

PURPOSE: Side-specific systematic lymphadenectomy is suggested if sentinel lymph node (SLN) mapping failed in early stages endometrial cancer. This study aimed to evaluate the risk factors associated with failed mapping which may lead to modify SLN mapping technique, increase the success of SLN mapping and reduce the necessity of systematic lymphadenectomy. METHODS: Patients with early stage endometrial cancer were included in this study. All patients underwent SLN mapping with indocyanine green/near-infrared compatible surgical platforms. Indocyanine green was injected intracervical. "Bilateral mapping" and "failed bilateral SLN mapping (unilateral or bilateral failed mapping)" groups were compared for demographic, clinical, surgical, and pathological features. RESULTS: 101 cases were analyzed. The overall, unilateral, and bilateral SLN detection rates were 94.1%, 19.8%, and 74.3%, respectively. The failed (unilateral or no mapping) bilateral detection rate was 25.7%. Failed bilateral mapping rates were higher in patients with longer cervical and uterine longitudinal lengths, deep myometrial invasion and larger tumor size without statistical significance. Body mass index and operation type were not related with failed mapping. Increasing number of operations or injection of larger volume of indocyanine green (4 mL vs. 2 mL) did not improve mapping rate significantly. CONCLUSION: Cervical indocyanine green injection may overcome the negative effect of obesity on bilateral mapping. Although there was a negative correlation trend between the longitudinal cervical and uterine lengths and bilateral mapping, this possible relation needs to be confirmed in further studies.

Extrapelvic Sentinel Lymph Nodes in Endometrial Cancer Patients With Unmapped Pelvic Side: A Brief Report.

OBJECTIVE: The aim of the study was to evaluate extrapelvic sentinel lymph nodes (SLNs) in clinical early-stage endometrial cancer patients with unmapped pelvic side(s) during fluorescent imaging-based sentinel mapping. MATERIALS AND METHODS: Eligible patients underwent sentinel mapping using cervical injection of indocyanine green and near-infrared florescent imaging compatible endoscopic systems. Pelvic SLNs were identified and resected. If bilateral mapping was not achieved, upper lymph nodes areas including presacral, upper common iliac, and para-aortic caval regions were explored for any SLN. Systematic lymphadenectomy was performed after applying SLN algorithm steps. RESULTS: In 24 of 101 patients, bilateral pelvic mapping was not achieved. Bilateral unmapping was seen in 4 of 24 and unilateral pelvic side mapping in 20 of 24 patients. There was no extrapelvic SLN among 4 cases with bilateral pelvic unmapping, whereas 8 (40%) of 20 patients with unilateral pelvic mapping had extrapelvic SLNs. Five of extrapelvic SLNs were in presacral, 2 in upper common iliac, and 1 in paracaval regions. CONCLUSIONS: Observing for extrapelvic SLNs in cases with unmapped pelvic side(s) could increase detection rate of SLN mapping in clinical early-stage endometrial cancer.

Prognostic factors for disease-free and overall survival of patients with uterine carcinosarcoma.

BACKGROUND: Uterine carcinosarcoma (UCS) is a relatively rare and very aggressive tumor. The predictors of survival for patients with UCS have not been determined clearly yet. The aim of the present study was to investigate the possible predictors of disease-free survival (DFS) and overall survival (OS) for patients with UCS. METHODS AND MATERIALS: All patients with UCS who were treated surgically at a university-based Gynecology Oncology Clinic between January 2008 and December 2014 were recruited into this retrospective cohort study. Data regarding clinical, pathologic and treatment information were obtained retrospectively from hospital records. The Kaplan-Meier method was used to calculate DFS and OS, and Cox regression analysis was performed to define the effects of risk factors on survival. RESULTS: A total of 88 UCS patients with a median age of 64.5 years were included in the study. Forty-seven (53.4%) patients were diagnosed with stage III disease and seven (7.9%) with stage IV disease. The median follow-up time was 16 months. Among all patients, 60 (68.1%) underwent lymphadenectomy. Optimal cytoreductive surgery was achieved in 67 (76.1%) patients. Stepwise variable selection Cox regression analysis showed that lymph node metastasis was associated with poor DFS (hazard ratio 6.524; 95% CI 2.625-16.211; P < 0.001) and OS (hazard ratio 6.993; 95% CI 2.631-18.587; P < 0.001). Subgroup analysis in both early and advanced-stage diseases revealed no significant impact of risk factors on survival. CONCLUSIONS: Lymph node metastasis is the most significant prognostic factor associated with poor DFS and OS in UCS patients.

Preoperative 18F-Fluorodeoxyglucose Positron Emission Tomography/CT in Prediction of Uterine Risk Factors and Lymph Node Metastasis: An Analysis of 111 Endometrioid Endometrial Cancer Patients.

INTRODUCTION: This study evaluated the role of 18F-fluorodeoxyglucose (FDG) positron emission tomography/CT (PET/CT) in the detection of lymph node metastases and the association between uterine maximum standardized uptake values (SUVmax) and the histopathological features in endometrial cancer patients. MATERIALS AND METHODS: Patients with endometrioid endometrial cancer underwent preoperative 18F-FDG PET/CT imaging and were staged surgically. 18F-FDG PET/CT findings were compared with final pathology reports. Grade 3 histology or grade 2 histology with myometrial invasion ≥50% was established as a high risk feature. RESULTS: One hundred and eleven patients were analysed. Sensitivity, specificity, accuracy, positive predictive value (PPV) and negative predictive value (NPV) of 18F-FDG PET/CT in the detection of lymph node metastasis in all patients (n = 111) were 67, 96, 93, 60 and 97%, respectively. In the high-risk group, sensitivity, specificity, accuracy, PPV and NPV of 18F-FDG PET/CT were 75, 92, 91, 60 and 96%, respectively. Uterine SUVmax was found to be associated with myometrial invasion, grade and cervical stromal involvement. CONCLUSIONS: 18F-FDG PET/CT has limited sensitivity and accuracy in detecting lymph node metastasis. Therefore, as of now, it is not accepted as a modality that can replace lymphadenectomy. SUVmax values can predict high-risk factors.

Expression of CD44 variant 6 and its prognostic value in benign and malignant endometrial tissue.

PURPOSE: CD44 expression in both the early and metastatic phases of many epithelial and non-epithelial cancers is strongly prognostic. The objective of the study is to evaluate whether there is any relationship between the expression of CDD44v6 and endometrial cancer (EC) staging and prognosis. METHODS: This retrospective study included 60 EC patients for whom surgical staging was performed between 2000 and 2006. Twenty-eight randomly selected patients with normal endometria served as the control group. We immunohistochemically evaluated membranous and cytoplasmic CD44v6 staining in tissue paraffin blocks. The results were graded as positive or negative. RESULTS: Membranous staining in both advanced and early stage EC patients was significantly higher than that in the control group (p = 0.002). The extent of either membranous or cytoplasmic staining in both advanced- and early stage patients did not differ significantly by age, tumor grade, stage, extent of myometrial invasion, lymph node involvement, cytology, adnexal involvement, or omental spreading. In advanced-stage patients, neither papillary serous not clear cell cancers exhibited cytoplasmic staining. CONCLUSIONS: CD44v6 membranous staining can be useful for differentiating malignant from benign endometrial tissue. However, staining is not associated with EC staging or prognosis.

Nomogram with potential clinical use to predict lymph node metastasis in endometrial cancer patients diagnosed incidentally by postoperative pathological assessment.

PURPOSE: To determine the clinical and pathological risk factors for lymph node metastasis (LNM) in patients with endometrial cancer and to create a nomogram to predict LNM in patients without surgical staging. METHODS: All patients with endometrial adenocarcinoma who were treated surgically at a university based gynecologic oncology clinic between January 2011 and December 2014 were recruited. Women with endometrial adenocarcinoma who were surgically staged including lymphadenectomy were included in the study. Data regarding clinical and pathological risk factors were recorded. The histopathologic slides from the staging surgeries were re-evaluated microscopically by a gynecologic pathologist for all parameters along with lymphovascular space invasion (LVSI). RESULTS: A total of 279 patients with endometrial cancer were analyzed. Among those, 31 (11.1%) had lymph node metastasis. According to the univariate analyses, elevated CA 125 (>35 U/mL), LVSI, myometrial invasion ≥50%, grade 3 disease, non-endometrioid type, and cervical stromal involvement were significantly associated with LNM. The multivariate logistic regression analysis showed that LVSI, non-endometrioid type, elevated CA 125, and cervical stromal involvement increased the risk of LNM. However, myometrial invasion and grade did not significantly affect the risk of LNM. A nomogram to predict LNM was constructed using these factors (concordance index 0.92). CONCLUSIONS: LVSI is the most important predictor for LNM. The present nomogram can be useful to decide if adjuvant therapy is required for patients who undergo simple hysterectomy for a benign etiology and incidentally diagnosed with endometrial cancer by pathological evaluation.

Does Lymphadenectomy Improve Survival in Uterine Leiomyosarcoma?

INTRODUCTION: The role of lymphadenectomy in the management of uterine leiomyosarcoma (LMS) is controversial. We aimed to identify whether lymph node dissection (LND) has any survival benefit in uterine LMS. METHODS: Data of 95 patients with histologically proven uterine LMS from 2 tertiary centers (1993 through 2009) were retrospectively analyzed. Kaplan-Meier and Cox proportional hazards regression models were used for analyses. RESULTS: Mean age was 51.5 years. Thirty-six (37.9%) underwent LND. The median lymph node count was 54. Eight (22.2%) patients had lymphatic metastasis. Median follow-up was 26 months. Sixty-two (65%) patients had recurrence and 48 (50.5%) died. Median disease-free survival (DFS) was 19 months for both group of patients who had or did not have LND, and median overall survival (OS) was 29 and 26 months, respectively (P = 0.4). Five-year DFS was 35.9% vs 26.8% (P = 0.4), and 5-year OS was 45.4% vs 43.8% (P = 0.22) for the groups. Multivariate analyses did not reveal a single independent prognostic factor in respect to DFS or OS. CONCLUSION: Higher rate of lymph node metastasis in patients with extrauterine disease indicated the importance of LND in LMS. However, the survival benefit of lymphadenectomy could not be shown.

Prognostic predictors and spread patterns in adult ovarian granulosa cell tumors: a multicenter long-term follow-up study of 108 patients.

PURPOSE: To identify prognostic predictors and spread patterns in adult ovarian granulosa cell tumors (OGCTs). METHODS: Available retrospective data of 108 OGCT patients managed at three centers between January 1, 1991 and December 31, 2010 were abstracted and analyzed. RESULTS: Stage distributions at diagnosis for stage I, II and III OGCT were 84.3, 5.4, and 9.3 %, respectively. Optimal cytoreduction with no macroscopically visible disease was achieved in 99/108 (91.6 %) patients. The median disease-free interval to first recurrence was 61 months. The overall 5- and 10-year survival rates were 93.3 and 90.9 %, respectively. Disease recurred in 18 (16.6 %) patients, and 8 (7.4 %) patients died of their disease. The first recurrence sites included the pelvic peritoneum (n = 10), liver/liver-capsule (n = 5), rectosigmoid colon (n = 4), retroperitoneal lymph nodes (n = 3), omentum (n = 3), small bowel mesenterium (n = 2), and vaginal cuff (n = 2). Multiple-site recurrence was observed in 9/18 (50 %) patients. Secondary cytoreduction requiring extensive surgery was performed in 14 patients with an optimality rate of 71.4 %. The remaining four patients received only chemotherapy. Multivisceral approaches, including pelvic peritonectomy (n = 9; 64.2 %), rectosigmoid resection (n = 3; 21.4 %), and segmental liver capsule resection (n = 2; 14.2 %) were performed more frequently during the secondary surgery. Definitive retroperitoneal lymph node metastasis rates at the initial and recurrent settings were 5.1 % (3/58) and 21.4 % (3/14), respectively. Both stage and residual tumor status were significantly associated with recurrence in univariate and multivariate analyses. CONCLUSIONS: Stage and residual tumor status are predictors of recurrence. Pelvic peritoneal, nodal and hepatic involvement, and multiple-site spread patterns requiring extensive cytoreductive surgery are likely associated with recurrence of OGCTs.

Pregnancy complicated by a Krukenberg tumor with an undetermined origin and its management.

Krukenberg tumor in pregnancy is very rare and management of this condition is a dilemma for physicians. Moreover, the existence of a primary Krukenberg tumor is still in debate. Herein, we present a 29-year-old woman at 29 weeks of pregnancy, admitted with premature labor and revealed to have a signet ring cell ovarian tumor with an undetermined primary origin. A primary Krukenberg tumor or a Krukenberg tumor with an undetermined origin has not been previously reported in a pregnant patient. By virtue of the controversy, we are not eager to use the term 'primary Krukenberg tumor' for this case, although the possibility of the existence of this kind of tumor cannot be totally ignored.

Long-term oncological and reproductive outcomes of fertility-sparing cytoreductive surgery in females aged 25 years and younger with malignant ovarian germ cell tumors.

AIM: To evaluate the long-term oncological and reproductive outcomes of patients aged 25 years and younger who were treated by fertility-sparing cytoreductive surgery (FSCS) plus adjuvant chemotherapy (ACT) or observation alone for malignant ovarian germ cell tumors (MOGCT). METHODS: Records of 42 eligible female patients treated for MOGCT between 1 May 1995 and 31 December 2010 at two centers were analyzed retrospectively. A telephone questionnaire was performed to gather reproductive and menstrual history. RESULTS: One patient was treated without FSCS and two patients were lost to follow-up. The mean age of the remaining 39 patients was 18.4 ± 3.2 years. Eighteen of the tumors were histologically pure dysgerminomas (PD) and 21 were non-dysgerminomatous tumors (non-DT). Thirteen patients (33%) presented with stage II-III disease. Optimal cytoreduction was achieved in 34 of the 39 patients (87%). Systematic pelvic and para-aortic lymphadenectomy was performed in 31 of the 39 patients (79.5%). The frequency of lymph node metastasis was 29% (9/31). Twenty-seven patients (69.2%) received ACT. Disease recurred in six (15.3%) patients, all in the non-DT group. Four of six underwent secondary optimal FSCS followed by chemotherapy. Retroperitoneal nodal recurrence was detected in two of these four patients (50%). Four deaths occurred, three due to chemoresistant aggressive disease and one due to secondary acute myelocytic leukemia. The overall survival rates for patients with PD and non-DT were 100% and 81.4%, respectively. Twenty-three of 27 patients who received ACT continued their regular menses. Sixteen spontaneous pregnancies and one pregnancy by intrauterine insemination were achieved by 21 patients who attempted conception. CONCLUSION: Either primary or secondary FSCS followed by ACT seems to be a feasible and safe approach to preserving future fertility and hormonal function in young patients with MOGCT.

Is adjuvant chemotherapy necessary for 2014 FIGO stage IC adult granulosa cell tumor?: Multicentric Turkish study.

AIM: The aim of our study is to examine the clinical, surgical, and pathological factors of stage 1C adult granulosa cell tumor (AGCT) patients and to investigate the effects of adjuvant therapy on recurrence and survival rates in this patient group. METHODS: Out of a total of 415 AGCT patients treated by 10 tertiary oncology centers participating in the study, 63 (15.2%) patients with 2014 FIGO stage IC constituted the study group. The FIGO 2014 system was used for staging. Patient group who received adjuvant chemotherapy was compared with patient group who did not receive adjuvant chemotherapy in terms of disease-free survival (DFS), and disease-specific survival. RESULTS: The 5-year DFS of the study cohort was 89%, and the 10-year DFS was 85%. Those who received adjuvant chemotherapy and those who did not were similar in terms of clinical, surgical and pathological factors, except for peritoneal cytology. In the univariate analysis, none of the clinical, surgical or pathological factors were significant for DFS. Adjuvant chemotherapy and type of treatment protocol had no impact on DFS. CONCLUSION: Adjuvant chemotherapy was not associated with improved DFS and overall survival in stage IC AGCT. Multicentric and randomized controlled studies are needed for early stage AGCT in order to confirm these results and reach accurate conclusions.

Prognostic factors of adult granulosa cell tumors of the ovary: a Turkish retrospective multicenter study.

OBJECTIVE: To define the clinical, histopathological features and the prognostic factors affecting survival in patients with adult granulosa cell tumors of the ovary (AGCT). METHODS: A 322 patients whose final pathologic outcome was AGCT treated at nine tertiary oncology centers between 1988 and 2021 participated in the study. RESULTS: The mean age of the patients was 51.3±11.8 years and ranged from 21 to 82 years. According to the International Federation of Gynecology and Obstetrics 2014, 250 (77.6%) patients were stage I, 24 (7.5%) patients were stage II, 20 (6.2%) patients were stage III, and 3 (7.8%) were stage IV. Lymphadenectomy was added to the surgical procedure in 210 (65.2%) patients. Lymph node involvement was noted in seven (3.3%) patients. Peritoneal cytology was positive in 19 (5.9%) patients, and 13 (4%) had metastases in the omentum. Of 285 patients who underwent hysterectomy, 19 (6.7%) had complex hyperplasia with atypia/endometrial intraepithelial neoplasia, and 8 (2.8%) had grade 1 endometrioid endometrial carcinoma. It was found that 93 (28.9%) patients in the study group received adjuvant treatment. Bleomycin, etoposide, cisplatin was the most commonly used chemotherapy protocol. The median follow-up time of the study group was 41 months (range, 1-276 months). It was noted that 34 (10.6%) patients relapsed during this period, and 9 (2.8%) patients died because of the disease. The entire cohort had a 5-year disease-free survival (DFS) of 86% and a 5-year disease-specific survival of 98%. Recurrences were observed only in the pelvis in 13 patients and the extra-abdominal region in 7 patients. The recurrence rate increased 6.168-fold in patients with positive peritoneal cytology (95% confidence interval [CI]=1.914-19.878; p=0.002), 3.755-fold in stage II-IV (95% CI=1.275-11.063; p=0.016), and 2.517-fold in postmenopausal women (95% CI=1.017-6.233; p=0.046) increased. CONCLUSION: In this study, lymph node involvement was detected in 3.3% of patients with AGCT. Therefore, it was concluded that lymphadenectomy can be avoided in primary surgical treatment. Positive peritoneal cytology, stage, and menopausal status were independent prognostic predictors of DFS.

Cervical stromal involvement can predict survival in advanced endometrial carcinoma: a review of 67 patients.

PURPOSE: To assess clinical, surgical and pathologic variables in survival of advanced endometrial cancer. METHODS: Sixty-seven advanced-stage (stages III and IV according to FIGO 2009) endometrial cancer cases were evaluated retrospectively. The effects on survival of age, histologic subtype, stage, grade, myometrial invasion, optimal cytoreduction, parity and cervical involvement were analyzed. RESULTS: Cervical involvement (P = 0.033) and nulliparity (P = 0.042) were worsening features in terms of survival. In 56 cases (83.5%) optimal cytoreduction could be achieved and survival was significantly longer in this group than the group who were not optimally cytoreduced (mean 30.4 vs. 9.6 months) (P < 0.01). Depth of myometrial invasion, histologic type of tumor, stage, grade, and age younger or older than 60 years were not found to be related to survival. Neither adjuvant therapy type nor their combination were superior to each other for improving survival. CONCLUSIONS: Cervical stromal involvement is a poor prognostic factor in cases of advanced endometrial carcinoma. Further studies are required to describe the effect of different surgical approaches such as radical hysterectomy on survival in the presence of cervical stromal invasion.