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.

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

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

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.

Factors associated with the involvement of lymph nodes in low-grade serous ovarian cancer.

BACKGROUND AND OBJECTIVES: Evaluating nodal metastases in low-grade serous ovarian cancer (LGSOC) patients. METHODS: Women with LGSOC who had undergone primary cytoreductive surgery comprising systematic pelvic-paraaortic lymphadenectomy were included. Data were obtained retrospectively from 12 oncology centers. RESULTS: One hundred and forty-eight women with LGSOC who had undergone comprehensive surgical staging were included. Seventy-one (48.0%) patients had metastatic lymph nodes. Preoperative serum CA-125 levels of ≥170 U/ml (odds ratio [OR]: 3.84; 95% confidence interval [CI]: 1.22-12.07; p = 0.021) and presence of lymphovascular space invasion (LVSI) (OR: 13.72; 95% CI: 3.36-55.93; p < 0.001) were independent predictors of nodal metastasis in LGSOC. Sixty (40.5%) patients were classified to have apparently limited disease to the ovary/ovaries. Twenty (33.3%) of them were upstaged after surgical staging. Twelve (20.0%) had metastatic lymph nodes. Presence of LVSI (OR: 12.96; 95% CI: 1.14-146.43; p = 0.038) and preoperative serum CA-125 of ≥180 U/ml (OR: 7.19; 95% CI: 1.35-38.12; p = 0.02) were independent predictors of lymph node metastases in apparent Stage Ⅰ disease. CONCLUSIONS: Clinicians may consider to perform a reoperation comprising systematic lymphadenectomy in patients who had apparently limited disease to the ovary/ovaries and had not undergone lymphadenectomy initially. Reoperation may be considered particularly in patients whose preoperative serum CA-125 is ≥180 U/ml and/or whose pathological assessment reported the presence of LVSI.

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

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

The safety of major gynaecologic cancer surgery without routine preoperative COVID-19 testing in the COVID-19 era: a multicentre, retrospective, case-control study.

Our goal was to address the safety of major gynaecologic cancer surgery without routine preoperative COVID-19 testing in the COVID-19 era. The databases of seven gynaecologic cancer centres were searched in order to identify all consecutive gynaecologic cancer patients undergoing major surgery between March 11, 2020 and May 15, 2020 for this retrospective, case-control study. The case group consisted of patients with histopathologically confirmed gynaecologic cancers, and each case was matched with two counterparts who had undergone primary surgery before the COVID-19 pandemic. The case and the control groups were compared in terms of length of hospital stay, admission to the intensive care unit (ICU), intraoperative and postoperative complications.During the study period, 154 women with gynaecologic cancer undergoing major surgery were identified. Although the case group had more co-morbidities compared to the control group (103/154 vs. 178/308, respectively; p = .04), the median length of hospital stays, the rate of ICU admission, intraoperative complication rates and postoperative complication rates were similar in the two groups. Gynaecologic cancer surgery may be performed safely in the COVID-19 era with similar rates of ICU admission, intraoperative and postoperative complications compared to the patients operated before the COVID-19 pandemic.IMPACT STATEMENTWhat is already known on this subject? Many societies have announced their guidelines about the surgical management of gynaecologic cancer patients during the COVID-19 pandemic. However, most of them are not evidence-based and mostly on expert opinions.What do the results of this study add? The main findings of this retrospective, case-control study indicate that the short-term (30 day) outcomes of gynaecologic cancer patients undergoing major surgery in the COVID-19 era are similar to those who had been operated before the COVID-19 pandemic. The length of hospital stays, the rates of admission to the ICU, intraoperative and postoperative complications were comparable between women undergoing major gynaecologic cancer surgery in the COVID-19 era and the women who had been operated before the pandemic.What are the implications of these findings for clinical practice and/or further research? We can suggest that definitive surgery may be performed for gynaecologic cancer patients in the COVID-19 era if the resources permit and appropriate precautions such as social distancing, isolation and the use of personal protective equipment are taken.

Radiomics analysis of uterine tumors in 18F-fluorodeoxyglucose positron emission tomography for prediction of lymph node metastases in endometrial carcinoma.

BACKGROUND: In this single-center study, we aimed to analyze texture features of primary uterine lesions on 18F-FDG PET/CT to predict lymph node metastases. METHODS: Totally, 157 (mean age: 62 ± 10.2 years) patients were included in the analysis. Histopathological examination results were considered as the standard reference for nodal involvement. On 18F-FDG PET/CT images, only the primary tumor was segmented. SUVmax, SUVmean, SUVpeak, MTV, and TLG of primary uterine lesions were calculated for analyses. For texture analysis first, second, and higher-order texture features were calculated. RESULTS: Mean diameter of primary uterine lesions was calculated as 35± 18.1 mm. Lymph node metastases were detected in 19% of patients in histopathological examination of surgical materials. While 26 patients had pelvic lymph node metastases, 19 patients had additional paraaortic lymph node metastases. On radiomics analysis for 20 features, a significant difference was found between patients with and without lymph node metastasis. With using data mining methods GLZLM ZLNU, EntropyGLCM, Entropyhisto, GLRLM LRHGE, GLZLM HGZE, GLZLM SZHGE, GLRLM HGRE, GLRLM SRHGE were found significant radiomics features to predict lymph node metastasis with a diagnostic accuracy of 0.8. DISCUSSION: The radiomics analysis of intratumoral heterogeneity is a promising method for improving triage of the patients for lymph node dissection in endometrial carcinoma.

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.

Impact of cytoreductive surgery on survival of patients with low-grade serous ovarian carcinoma: A multicentric study of Turkish Society of Gynecologic Oncology (TRSGO-OvCa-001).

BACKGROUND AND OBJECTIVES: The aim of this study was to analyze the factors affecting recurrence-free (RFS) and overall survival (OS) rates of women diagnosed with low-grade serous ovarian cancer (LGSOC). METHODS: Databases from 13 participating centers in Turkey were searched retrospectively for women who had been treated for stage I-IV LGSOC between 1997 and 2018. RESULTS: Overall 191 eligible women were included. The median age at diagnosis was 49 years (range, 21-84 years). One hundred seventy-five (92%) patients underwent primary cytoreductive surgery. Complete and optimal cytoreduction was achieved in 148 (77.5%) and 33 (17.3%) patients, respectively. The median follow-up period was 44 months (range, 2-208 months). Multivariate analysis showed the presence of endometriosis (p = .012), lymphovascular space invasion (LVSI) (p = .022), any residual disease (p = .023), and the International Federation of Gynecology and Obstetrics (FIGO) stage II-IV disease (p = .045) were negatively correlated with RFS while the only presence of residual disease (p = .002) and FIGO stage II-IV disease (p = .003) significantly decreased OS. CONCLUSIONS: The maximal surgical effort is warranted for complete cytoreduction as achieving no residual disease is the single most important variable affecting the survival of patients with LGSOC. The prognostic role of LVSI and endometriosis should be evaluated by further studies as both of these parameters significantly affected RFS.

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.

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.

Carcinosarcoma of the ovary compared to ovarian high-grade serous carcinoma: impact of optimal cytoreduction and standard adjuvant treatment.

OBJECTIVE: The purpose of this retrospective study was to compare the prognoses of women with ovarian carcinosarcoma (OCS) who had optimal cytoreductive surgery followed by platinum plus taxane combination chemotherapy to those of women with ovarian high-grade serous carcinoma (HGSC) treated in the same manner. METHODS: A multicenter, retrospective department database review was performed to identify patients with OCS at eight gynecologic oncology centers in Turkey. A total of 54 women with OCS who had undergone optimal cytoreductive surgery followed by platinum plus taxane combination chemotherapy between 1999 and 2017 were included in this case-control study. Each case was matched to two women with ovarian HGSC who had undergone optimal cytoreductive surgery followed by platinum plus taxane combination chemotherapy. The Kaplan-Meier method was used to generate survival data. Factors predictive of outcome were analysed using Cox proportional hazards models. RESULTS: Median disease-free survival (DFS) was 29 months [95% confidence interval (CI) 0-59, standard error (SE) 15.35] versus 27 months (95% CI 22.6-31.3, SE 2.22; p = 0.765) and median overall survival (OS) was 62 versus 82 months (p = 0.53) for cases and controls, respectively. For the entire cohort, the presence of ascites [hazard ratio (HR) 2.32; 95% CI 1.02-5.25, p = 0.04] and platinum resistance [HR 5.05; 95% CI 2.32-11, p < 0.001] were found to be independent risk factors for decreased OS. CONCLUSION: DFS and OS rates of patients with OCS and HGSC seem to be similar whenever optimal cytoreduction is achieved and followed by platinum plus taxane combination chemotherapy.

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.

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.

Effects of umbilical cord milking on the need for packed red blood cell transfusions and early neonatal hemodynamic adaptation in preterm infants born ≤1500 g: a prospective, randomized, controlled trial.

OBJECTIVE: The aim of this study was to evaluate the effects of umbilical cord milking (UCM) on the need for packed red blood cell (PRBC) transfusion and hematologic and hemodynamic parameters in very-low-birth-weight infants. METHODS: The infants were randomized into 2 groups: group 1 (UCM) and group 2 (control). The primary outcome was the number of PRBC transfusions during the first 35 days of life. The secondary outcome measures were the hemodynamic variables during the first 24 hours of life. RESULTS: A total of 44 infants were included with 22 infants in each group. Two of 21 infants in group 1 and 4 of 21 infants in group 2 received transfusion in the first 3 days of life (P=0.384). The number and volume of PRBC transfusions were similar in both groups. However, the levels of hemoglobin (Hb) at the first and 24th hour of life were significantly higher in group 1. Phlebotomy volume was found as a statistically significant risk factor for the need for PRBC transfusion (P=0.005). CONCLUSIONS: UCM in delivery room results in a higher Hb level in the first day of life. In these groups of infants, phlebotomy losses may impact the transfusion need.