Why do some patients with stage 1A and 1B endometrial endometrioid carcinoma experience recurrence? A retrospective study in search of prognostic factors.

OBJECTIVES: Endometrial endometrioid carcinoma (EEC) is the most encountered subtype of endometrial cancer (EC). Our study aimed to investigate the factors affecting recurrence in patients with stage 1A and 1B EEC. MATERIAL AND METHODS: Our study included 284 patients diagnosed with the International Federation of Gynecology and Obstetrics stage 1A/1B EEC in our center from 2010 to 2018. The clinicopathological characteristics of the patients were obtained retrospectively from their electronic files. RESULTS: The median age of the patients was 60 years (range 31-89). The median follow-up time of the patients was 63.6 months (range 3.3-185.6). Twenty-two (7.74%) patients relapsed during follow-up. Among the relapsed patients, 59.1% were at stage 1A ECC, and 40.9% were at stage 1B. In our study, the one-, three-, and five-year recurrence-free survival (RFS) rates were 98.9%, 95.4%, and 92.9%, respectively. In the multivariate analysis, grade and tumor size were found to be independent parameters of RFS in all stage 1 EEC patients. Furthermore, the Ki-67 index was found to affect RFS in stage 1A EEC patients, and tumor grade affected RFS in stage 1B EEC patients. In the time-dependent receiver operating characteristic curve analysis, the statistically significant cut-off values were determined for tumor size and Ki-67 index in stage 1 EEC patients. CONCLUSIONS: Stage 1-EEC patients in the higher risk group in terms of tumor size, Ki-67, and grade should be closely monitored for recurrence. Defining the prognostic factors for recurrence in stage 1 EEC patients may lead to changes in follow-up algorithms.

The impact of Ki-67 index, squamous differentiation, and several clinicopathologic parameters on the recurrence of low and intermediate-risk endometrial cancer.

Endometrial endometrioid carcinoma (EEC) represents approximately 75-80% of endometrial carcinoma cases. Three hundred and thirty-six patients with EEC followed-up in the authors' medical center between 2010 and 2018 were included in our study. Two hundred and seventy-two low and intermediate EEC patients were identified using the European Society for Medical Oncology criteria and confirmed by histopathological examination. Recurrence was reported in 17 of these patients. The study group consisted of patients with relapse. A control group of 51 patients was formed at a ratio of 3:1 according to age, stage, and grade, similar to that in the study group. Of the 17 patients with recurrent disease, 13 patients (76.5%) were Stage 1A, and 4 patients (23.5%) were Stage 1B. No significant difference was found in age, stage, and grade between the case and control groups (p > 0.05). Body mass index, parity, tumor size, lower uterine segment involvement, SqD, and Ki-67 index with p<0.25 in the univariate logistic regression analysis were included in the multivariate analysis. Ki-67 was statistically significant in multivariate analysis (p = 0.018); however, there was no statistical significance in SqD and other parameters. Our data suggest that the Ki-67 index rather than SqD needs to be assessed for recurrence in patients with low- and intermediate-risk EEC.

Omental Micrometastasis in Endometrial Cancer.

INTRODUCTION: Although there are several reports on omentum metastasis, limited studies have evaluated omental micrometastases, particularly isolated microscopic metastases in endometrial cancer (EC). We performed this study to assess the frequency of omental micrometastasis in EC, especially when the omentum is the only site of extrauterine spread. METHODS: A retrospective study was conducted to assess cases of EC with an omental sample during primary surgical treatment for EC at the Gynecological Oncology Unit, Uludag University Hospital, Bursa, Turkey, between January 2005 and May 2018. RESULTS: In total, 435 patients fulfilled the inclusion criteria, which comprised a complete surgical staging. The prevalence of omental metastases was 5.3% (n = 23), regardless of the subtype or clinical stage. Omental micrometastasis was detected in four cases (17.4%). In half of these patients, the omentum was the only site of disease outside the uterus, with an estimated 0.46% of isolated omental involvement. The grade of the endometrioid tumor was found to be statistically correlated with omental metastases (p = 0.01). There was a significant correlation between omental metastasis and positive peritoneal cytology, as well as adnexal involvement (p = 0.001 and p = 0.03, respectively). CONCLUSION: We recommend omentectomy routinely in serous EC. In addition, we suggest selective omentectomy in patients with EC who have concomitant adnexal involvement or grade 3 tumors.

Comparison Of Early-Stage High-Grade Serous Primary Fallopian Tube Cancers and Epithelial Ovarian Cancers: A Multicenter Study.

INTRODUCTION: We compared the disease free-survival (DFS) and overall survival (OS) rates of patients with high-grade serous primary fallopian tube cancer (HG-sPFTC) and high-grade serous epithelial ovarian cancer (HG-sEOC). METHODS: 22 early-stage cancer patients (International Federation of Gynecology and Obstetrics (FIGO) stages I-II) with HG-sPFTC were retrospectively evaluated. In addition, 44 control patients diagnosed with HG-sEOC were matched to these patients with respect to tumor stage at diagnosis. All patients underwent complete surgical staging, followed by adjuvant chemotherapy. Kaplan-Meier curves were used to generate survival data. RESULTS: The mean age of HG-sPFTC patients was 59.4 ± 6.2 years, and that of HG-sEOC patients 55.2 ± 11.0 years (p = 0.002). All patients underwent 6 cycles of platinum-based adjuvant chemotherapy. All operations were optimal. The 5-year DFSs were 77.3% for HG-sPFTC patients and 75% for HG-sEOC patients (p = 1.00).The 5-year OS rates were 81.8% in women with HG-sPFTC and 77.3% in those with HG-sEOC (p = 0.75). CONCLUSION: The DFS and OS rates of patients with early-stage (FIGO stages I and II) HG-sPFTC and HG-sEOC were similar. The surgical and adjuvant therapy management of these malignancies should be similar.

Wilms' tumor 1 protein expression in endometrial adenocarcinoma and endometrial intra-epithelial neoplasia.

AIM: To investigate the expression of Wilms' tumor 1 (WT1) protein in endometrial adenocarcinoma (EC) and endometrial intra-epithelial neoplasia (EIN). METHODS: WT1 protein expression was determined on immunohistochemistry in 30 EC patients and in 20 EIN patients. WT1 protein expression in proliferative (n = 7), secretory (n = 9) and atrophic endometrium (n = 9) and benign endometrial polyps (n = 28) was used as the control group. Cellular and vascular WT1 staining was scored semiquantitatively. RESULTS: Cellular WT1 staining was 67% and vascular positivity was 73% in the EC group. In the EIN group the cellular staining was 100% and vascular staining was 85%. Although all EIN samples were positive for cellular WT1 staining, median cellular staining score was similar to that of EC (median, 2; range, 1-3; IQR, 1.75 vs 2, 0-3, 0.75, respectively). Increasing EC grade and stage were not associated with cellular or vascular WT1 staining score. CONCLUSION: WT1 is expressed in EIN.

Comparison of risk of malignancy index (RMI), CA125, CA 19-9, ultrasound score, and menopausal status in borderline ovarian tumor.

OBJECTIVE: The aim of this study was to assess the prognostic values of risk of malignancy index (RMI IV), ultrasound score, menopausal status, and serum CA125 and CA19-9 level in patients with borderline ovarian tumor (BOT). METHODS: Fifty women having borderline ovarian tumor (BOT) and 5O individuals with benign adnexal mass were enrolled in this retrospective study. The sensitivity, specificity, positive predictive values, negative predictive values and diagnostic accuracy of preoperative serum levels of the CA125 and CA19-9, ultrasound findings and menopausal status, and RMI IV were calculated for prediction of discrimination between BOTs and benign adnexal masses and the results were compared. RESULTS: The RMI IV was the best method for discrimination between BOTs and benign adnexal masses and was more accurate than the other parameters. When Receiver Operator Characteristic area under the curves for menopausal status was analyzed, serum CA 125 and CA19-9 level, ultrasound score, RMI IV(CA125), and RMI IV(CA19-9) were, 0.580, 0.625, 0.548, 0.694, 0.734 and 0.711, respectively. The best RMI IV cut-off was found to be 200 for discrimination of benign and BOT lesions. In the RMI formulation, replacing CA125 with CA19-9 didn't affect RMI IV sensitivity and specificity for discrimination. CONCLUSION: Compared to ultrasound, menopausal status, CA-125, CA19-9, the RMI IV was found to be the best predictive method for differentiation of BOTs from benign adnexal masses. RMI IV cut-off value of 200 is suitable for differentiation of benign and BOT's.

GST (GSTM1, GSTT1, and GSTP1) polymorphisms in the genetic susceptibility of Turkish patients to cervical cancer.

OBJECTIVE: This work investigates the role of glutathione S-transferase M1 (GSTM1), glutathione S-transferase T1 (GSTT1), and glutathione S-transferase P1 (GSTP1) enzymes and polymorphisms, which are found in phase II detoxification reactions in the development of cervical cancer. METHODS: This study was conducted with 46 patients diagnosed with cervical cancer and 52 people with no cancer history. Multiplex PCR methods were used to evaluate the GSTM1 and GSTT1 gene polymorphism. However, the GSTP1 (Ile105Val) gene polymorphism was studied using a PCR-RFLP method. The patient and control groups were compared using a chi-square test with p<0.05. RESULTS: In the patient group, statistical significance was determined for gravidity (p=0.03), parity (p=0.01), and the number of living children (p=0.01) compared to the control group. The gene frequency of GSTM1, GSTT1, and GSTP1 polymorphisms was evaluated. We observed that GSTM1 and GSTT1 null genotype frequencies were 54.3% and 32.6% respectively, while GSTP1 (Ile/Val), (Ile/Ile), (Val/Val) genotype frequencies were 52%, 44%, and 4%, respectively, in the cervical cancer patients. No statistical variation was determined between the control and patient groups in terms of GSTM1, GSTT1, and GSTP1 polymorphisms (p>0.05). CONCLUSION: Our results demonstrate that GSTT1, GSTM1, and GSTP1 polymorphisms are not associated with cervical cancer in Turkish patients.

Splenectomy in cytoreductive surgery for advanced ovarian cancer.

METHODS: To evaluate the series of advanced ovarian cancer patients who underwent splenectomy as part of their surgery, a retrospective file review of 258 ovarian cancer cases were examined. RESULTS: There were 13 cases that underwent splenectomy. These patients constitute 5% of all and 8.8% of the advanced ovarian cancer patients. Seven cases had splenectomy as part of their initial cytoreductive surgery while 6 had surgery for recurrent disease. Splenectomy was performed to resect hilar and/or capsular involvement in 9 (69%) cases, while in 3 cases (23%) splenic injury during adjacent tumoral resection required splenectomy. One patient had splenectomy for infarcts and died after the surgery with systemic complications nonrelated to the surgery. No other serious morbidity was detected. Median survival of the patients was 34 months (1-120 months) from the initial diagnosis. Median survival was 18 months (1-78 months) after the splenectomy. Three patients were still alive with no evidence of disease 2, 5 and 6.5 years after the splenectomy. CONCLUSION: Splenectomy is a feasible and safe procedure. However, it should be reserved for patients in whom optimal cytoreductive results could be achieved.

A comparison of three histological grading systems in endometrial cancer.

METHODS: To compare the architectural, nuclear and International Federation of Gynecology and Obstetrics (FIGO) grading systems in endometrial cancer 70 consecutive patients with endometrial cancer were retrospectively reevaluated with three grading systems. RESULTS: Twenty-eight (40%), 27 (38.6%) and 14 (20%) cases were reported to have different grades when architectural vs nuclear, architectural vs. FIGO and nuclear vs. FIGO grading systems were compared in evaluation, respectively. Only 3 (42.8%) of the seven died patients had grade 3 in all three grading systems. Five-year survival rates were 95.7, 80, and 78.6% for architectural grade 1, 2 and 3, respectively. Same rates were 96.7, 90.5, and 78.9% for nuclear and 96, 91.7 and 81% for FIGO grading systems, respectively. CONCLUSIONS: Grades of the tumors often change when different grading systems are used. Postoperative treatment should be considered when at least one of the grading systems indicates poor differentiation.

Coexisting endometrial cancer in patients with a preoperative diagnosis of atypical endometrial hyperplasia.

AIM: To investigate the possibility of coexisting endometrial cancer (EC) in patients with atypical endometrial hyperplasia (AEH). METHODS: Forty-six consecutive women who underwent hysterectomy for AEH were analyzed. RESULTS: Final histopathological evaluation of hysterectomy specimens revealed EC in 11 patients (23.9%). Preoperative diagnosis of AEH was established by pipelle biopsy in eight patients and curettage was performed in the remaining patients. Of the patients with pipelle biopsy, two had a diagnosis of EC (25%), whereas nine women who underwent curettage, were further diagnosed as having EC (23.7%) (P > 0.05). Four (13.3%) of 30 women who had frozen sections at hysterectomy, were diagnosed with EC. Diagnosis of EC was missed in two patients (50%) at frozen section. In contrast, seven of 16 women (43.7%) who did not have frozen section, had EC. CONCLUSION: A relatively high incidence of EC is seen in patients with a diagnosis of AEH. Diagnostic results of pipelle biopsy and curettage were comparable. Frozen sections of hysterectomy specimens does not guarantee to exclude the possibility of EC, especially in patients with no myometrial invasion.

Successful salvage therapy of resistant gestational trophoblastic disease with etoposide, methotrexate, actinomycin-D, etoposide, cisplatin (EMA/EP).

A 26-year-old woman who had been treated for nonmetastatic gestational trophoblastic tumor with three courses of methotrexate with folinic acid rescue and had been lost to follow up for 4 years was referred with the fractional curettage diagnosis of choriocarcinoma that had been performed for abnormal vaginal bleeding. Her serum beta human chorionic gonadotropin (betahCG) was 706000 mIU/mL and there were multiple pulmonary metastatic foci. The uterus was 12 weeks pregnant-size and a 6 x 6-cm tumor mass was seen within the anterior uterine wall at ultrasonography. Following total abdominal hysterectomy etoposide, methotrexate, actinomycin-D, vincristine and cyclophosphamide (EMA/CO) regimen was given. Whole brain radiation of 30 Gy in 3 weeks for brain metastasis, discovered in magnetic resonance imaging was given after the first course. Since serum betahCG levels plateaued after three courses of chemotherapy and multiple pulmonary metastases persisted, treatment was shifted to etoposide, methotrexate, actinomycin-D, etoposide, cisplatin (EMA/EP) regimen. She was in remission after three courses of chemotherapy.

Angiogenesis in endometrial carcinoma: correlation with survival and clinicopathologic risk factors.

Association among angiogenesis, survival and clinicopathologic parameters in endometrial carcinoma was evaluated. Sixty patients who had been diagnosed as endometrial carcinoma, from 1993 to 1998, were included in the study. All patients had been surgically staged with bilateral pelvic and para-aortic lymph node dissection. All hysterectomy specimens were stained immunohistologically for factor VIII-related antigen. The area with the most intensified microvasculature was determined under low-power (x100) magnification, and the microvessel count of this area under high-power (x200) magnification was determined as the microvessel density (MVD) of the tumor. The mean MVD was 26.2 +/- 13.0 (range 6-68), and it was considered as high (n = 24; 40%), moderate (n = 19; 31.7%) and low (n = 17; 28.3%) when the MVD was >30, between 15-30 and <15, respectively. Statistical analysis included Mann-Whitney, Kruskal-Wallis and Spearman rank correlation tests. The Kaplan-Meier method was used to evaluate the difference between angiogenesis and survival. Multivariate analysis with the Cox regression model was used in MVD values and different clinicopathological parameters. There was positive correlation between MVD increase and surgicopathological stage (p < 0.05). A significant difference was seen between MVD increase and lymph node metastasis (p < 0.05). There were no differences between MVD and age, histological type, grade and lymphovascular invasion. MVD did not change in association with myometrial invasion depth. There was a significant difference in means of survival between the low and high MVD groups (p = 0.01). However, MVD was not an independent prognostic factor in multivariate analysis. Increased angiogenesis was found to be associated with advanced stage and decreased survival in endometrial carcinoma.

Plasma anti-oxidant status and lipid profile in non-gravida women with a history of pre-eclampsia.

OBJECTIVE: To investigate the total plasma anti-oxidant status, the plasma lipid profile and the uterine artery Doppler velocity waveform in formerly pre-eclamptic women. METHODS: Thirty-two formerly pre-eclamptic, non-gravida women constituted the study group, while 28 age-matched non-gravida women who had never had pre-eclampsia served as control subjects. On days 17-19 of their menstrual cycle, fasting plasma samples were collected for total anti-oxidant status (TAS) and lipid profile evaluation, and uterine artery Doppler velocity waveform studies were performed. Results were analyzed with Mann-Whitney U-test and Pearson correlation analysis. RESULTS: There was no significant difference between the groups in means of the uterine artery Doppler velocity waveforms and the plasma lipid levels, but body mass index values were significant (P < 0.005). The TAS value was subnormal in 72% of the formerly pre-eclamptic group and in 35% of the control group. The mean plasma TAS value was 1.20 +/- 0.05 mmol/L and was significantly lower in the study group when compared with the control group (P < 0.05). CONCLUSION: The current study reveals significantly decreased TAS in women with a history of pre-eclampsia, which may have an important role in pathophysiology.