Uterine papillary serous and clear cell carcinomas: Comparison of characteristics and clinical outcomes.

INTRODUCTION: To assess the rate of disease control and survival after adjuvant treatment in patients with uterine papillary serous (PSC) and clear cell carcinoma (CCC) and compare the results between these two subtypes. METHODS: The medical charts of 199 patients with de novo uterine PSC or CCC who underwent radiotherapy (RT) following surgery between 2001 and 2019 in three radiation oncology departments were retrospectively evaluated. Adjuvant treatment was decided by a multidisciplinary tumor board. All patients were planned to undergo adjuvant 4-6 cycles of chemotherapy with external beam RT (EBRT) and/or vaginal brachytherapy (VBT). RESULTS: Median age was 63 years for all, 64 years for PSC, and 59 years for CCC, respectively. Complete surgical staging was applied in 98% of patients. Histopathologic subtype was PSC in 142 (71%) and pure CCC in 57 (29%) patients, respectively. FIGO stage was I in 107 (54%), II in 35 (18%), and III in 57 (28%) patients, respectively. Lympho-vascular space invasion and positive peritoneal cytology (PPC) were present in 42% and 10% of patients, respectively. All patients but 23 (12%) underwent adjuvant chemotherapy. Median follow-up was 49.5 months for all patients, 43.9 months for patients with PSC, and 90.4 months for patients with CCC, respectively. During follow-up, 20 (10%) patients developed pelvic recurrence (PR) and 37 (19%) developed distant metastasis (DM). PSC subtype increased the PR and DM rates, although the latter not statistically significant. The 5-year overall survival and disease-free survival rate was 73% and 69% for all patients, 71% and 66% for patients with PSC, and 77% and 75% for patients with CCC, respectively. The difference was more prominent in patients with stage ≥ IB disease. In multivariate analysis, advanced age and PPC significantly decreased all survival rates. CONCLUSION: PSC has a worse prognosis than CCC with regard to pelvic and distant recurrence with a trend for decreased survival rates. Therefore, a more aggressive therapy is needed for patients with uterine PSC, particularly in patients with stage ≥ IB disease.

Could the Long-Term Oncological Safety of Laparoscopic Surgery in Low-Risk Endometrial Cancer also Be Valid for the High-Intermediate- and High-Risk Patients? A Multi-Center Turkish Gynecologic Oncology Group Study Conducted with 2745 Endometrial Cancer Cases. (TRSGO-End-001).

This study was conducted to compare the long-term oncological outcomes of laparotomy and laparoscopic surgeries in endometrial cancer under the light of the 2016 ESMO-ESGO-ESTRO risk classification system, with particular focus on the high-intermediate- and high-risk categories. Using multicentric databases between January 2005 and January 2016, disease-free and overall survivals of 2745 endometrial cancer cases were compared according to the surgery route (laparotomy vs. laparoscopy). The high-intermediate- and high-risk patients were defined with respect to the 2016 ESMO-ESGO-ESTRO risk classification system, and they were analyzed with respect to differences in survival rates. Of the 2745 patients, 1743 (63.5%) were operated by laparotomy, and the remaining were operated with laparoscopy. The total numbers of high-intermediate- and high-risk endometrial cancer cases were 734 (45%) patients in the laparotomy group and 307 (30.7%) patients in the laparoscopy group. Disease-free and overall survivals were not statistically different when compared between laparoscopy and laparotomy groups in terms of low-, intermediate-, high-intermediate- and high-risk endometrial cancer. In conclusion, regardless of the endometrial cancer risk category, long-term oncological outcomes of the laparoscopic approach were found to be comparable to those treated with laparotomy. Our results are encouraging to consider laparoscopic surgery for high-intermediate- and high-risk endometrial cancer cases.

Multi-institutional validation of the ESMO-ESGO-ESTRO consensus conference risk grouping in Turkish endometrial cancer patients treated with comprehensive surgical staging.

In this study, 683 patients with endometrial cancer (EC) after comprehensive surgical staging were classified into four risk groups as low (LR), intermediate (IR), high-intermediate (HIR) and high-risk (HR), according to the recent consensus risk grouping. Patients with disease confined to the uterus, ≥50% myometrial invasion (MI) and/or grade 3 histology were treated with vaginal brachytherapy (VBT). Patients with stage II disease, positive/close surgical margins or extra-uterine extension were treated with external beam radiotherapy (EBRT)±VBT. The median follow-up was 56 months. The overall survival (OS) was significantly different between LR and HR groups, and there was a trend between LR and HIR groups. Relapse-free survival (RFS) was significantly different between LR and HIR, LR and HR and IR and HR groups. There was no significant difference in OS and RFS rates between the HIR and HR groups. In HR patients, the OS and RFS rates were significantly higher in stage IB - grade 3 and stage II compared to stage III and non-endometrioid histology without any difference between the two uterine-confined stages and between stage III and non-endometrioid histology. The current risk grouping does not clearly discriminate the HIR and IR groups. In patients with comprehensive surgical staging, a further risk grouping is needed to distinguish the real HR group.Impact statementWhat is already known on this subject? The standard treatment for endometrial cancer (EC) is surgery and adjuvant radiotherapy (RT) and/or chemotherapy is recommended according to risk factors. The recent European Society for Medical Oncology (ESMO), European Society of Gynaecological Oncology (ESGO) and European Society for Radiotherapy and Oncology (ESTRO) guideline have introduced a new risk group. However, the risk grouping is still quite heterogeneous.What do the results of this study add? This study demonstrated that the current risk grouping recommended by ESMO-ESGO-ESTRO does not clearly discriminate the intermediate risk (IR) and high-intermediate risk (HIR) groups.What are the implications of these findings for clinical practice and/or further research? Based on the results of this study, a new risk grouping can be made to discriminate HIR and IR groups clearly in patients with comprehensive surgical staging.

Cytoreductive surgery including distal pancreatectomy with splenectomy in advanced stage ovarian cancer: Two centers analysis.

OBJECTIVE: Complex procedures such as distal pancreatectomy and splenectomy (DPS) may be required for R0 resection in patients with ovarian cancer (OC). These procedures can increase survival and cause serious morbidity. We aimed to present our experience in this field. MATERIALS AND METHODS: Thirteen patients who underwent DPS for OC between January 2004 and July 2018 in two centers (Hacettepe University Hospital, Etlik Hospital) were evaluated. Statistical analysis was performed using SPSS. RESULTS: The mean operative time was 310 min (220-570 min). None of the patients required transfusion. No perioperative mortality was observed. The mean postoperative hospital stay was 12 days (ranging from 8 to 33 days). The number of patients with early postoperative complications was four (30.7%). One of these patients was complicated by intestinal perforation, one with pancreatic fistula, one with pneumonia and the other with atelectasis. Other complications were observed conservatively. Ten patients underwent 6 cycles of platinum-based chemotherapy postoperatively. The median value of the postoperative chemotherapy period was 20 days (range 11-47 days). The median follow-up period was 46 months (2-144 months). Ten patients had recurrence. Eleven patients died of disease. Two patients are stil alive. Disease-free (DFS) and overall (OS) survival were 16 and 63 months, respectively. CONCLUSION: DPS for cytoreductive surgery is a procedure that increases morbidity, but most of the complications can be treated conservatively. Considering the increase in survival, it is considered to be a valuable procedure in upper abdominal disease.

How to triage HPV positive cases: Results of four million females.

OBJECTIVE: To evaluate the Turkey's nationwide HPV DNA screening program on the basis of first 4 million screened women. METHODS: Women over age 30 were invited for screening via HPV DNA and conventional cytology. Single visit screen strategy was used to collect for both screening and triage (extended genotyping and conventional pap-smear). RESULTS: A total of 4,099,230 patients had attended to HPV DNA cancer screening. 4.39% were found to be HPV DNA positive. The most common HPV type was 16, followed by 51, 31, 52, 56 and 18 at all age intervals and geographic regions. Cytology results were reported as "normal" in (69.2%), "inadequate sampling" in (16.6%) and as "abnormal (≥ASC-US)" in the remaining. Current Turkish screening with HPV DNA (referral to colposcopy with HPV 16 or 18 or any smear abnormality ≥ASC-US) gives overall PPV of 24.3% for ≥CIN2. Only Pap-Smear triage revealed PPV of 26.4% for ≥ASC-US thresholds. Comparison of different triage methods for ≥CIN2+ according to different HPV genotype revealed a PPV of 32,6% for HPV 16; 15,3% for HPV 18. This figure was 34.4%, 19.3%, 15.3% and 14.0% for HPV 33, 31, 45 and 35; respectively. CONCLUSION: This study involves the largest series in the world summarizing a real-world experience with primary HPV DNA screening and triage with a single visit. The results show the feasibility and applicability of such screening method in developing countries with acceptable colposcopy referral rates. Among triage tests, only pap-smear seems to be effective without a need for extended genotyping.

Correlation of Swede score colposcopy scoring system and histopathological results in patients with high-risk HPV infection other than HPV16 and 18.

OBJECTIVE: Triage with HPV genotyping has some caveats and debates for HPV positive cases other than 16 and 18. The Swede score colposcopic scoring system has not previously been evaluated in this group of patients. OBJECTIVE: To use the Swede score colposcopic scoring system to compare scores and final histopathological results in women who have undergone colposcopy owing to infection with high risk-HPVs other than HPV16 and 18 and to establish new cut-off values to predict pre-malignant lesions in this group of patients. METHODS: This study was conducted in 613 women undergoing colposcopic evaluation because of abnormal cervical cytology together with high-risk HPV infection. All patients referred were evaluated by an expert colposcopist, given a Swede score (using the Swede score colposcopic scoring system) by using five variables (acetowhiteness, margins plus surface, vessel pattern, lesion size, and iodine staining), and had at least one biopsy procedure (either colposcopically directed or by a loop electrical excision procedure). Sensitivity, specificity, positive predictive value, negative predictive value, likelihood ratio values, and receiver operating characteristic curves for each clinico-pathological variable to detect low-grade and high-grade squamous intra-epithelial lesions, and any squamous cell abnormality (low-grade + high-grade squamous intra-epithelial lesions) were evaluated individually. RESULTS: Final histopathological results of the patients were normal in 53.2% of cases, low-grade lesions in 32.5% of cases, and high-grade lesions in 14.4% of cases. Swede score was ≥8 (median 7.97) for high-grade lesions and ≥5 (median 5.06) for low-grade lesions. The area under the curve values (95% CI) of Swede scores for low-grade and high-grade squamous intra-epithelial lesions, and low-grade + high grade lesions were 0.92, 0.98, and 0.96, respectively. A Swede score cut-off value ≥6 had a sensitivity, specificity, positive predictive value, negative predictive value, and likelihood ratios of 92%, 98%, 93%, 98%, and 50 (22.6 to 110.8), respectively, for high-grade lesions at the final pathology (P<0.001). One high-risk HPV type (except 16 and 18) was no better than another for calculating the median Swede score during colposcopy (P=0.43). CONCLUSIONS: The Swede score colposcopic scoring system appears to be a useful tool for evaluating atypical cervical cytology in women with high-risk HPV infection other than HPV types 16 and 18.

Does tumor size have prognostic value in patients undergoing lymphadenectomy in endometrioid-type endometrial cancer confined to the uterine corpus?

Background/aim: We aimed to define the effect of tumor size on recurrence and survival rates in patients with stage I­II endometrioid-type endometrial cancer. Materials and methods: A total of 550 patients who had total abdominal hysterectomy, bilateral salpingo-oophorectomy, and pelvic-paraaortic lymphadenectomy were included. Patients with extrauterine spread, sarcomatous components, or synchronized tumor and those who did not undergo lymphadenectomy or did not have data on tumor size were excluded. Results: The median tumor size was 35 mm (range: 3­335 mm). According to the 2009 International Federation of Obstetrics and Gynecology (FIGO) criteria, 245 cases were defined as stage IA, 271 as stage IB, and 34 as stage II. The 5-year disease-free survival (DFS) rate was 92% and the 5-year disease-specific survival (DSS) rate was 99%. The effects of prognostic factors on DFS were evaluated. Older age, stage II disease, deep myometrial invasion, and receiving adjuvant radiotherapy were associated with decreased DFS. There was no statistically significant association between tumor size and DFS. The 5-year DFS for patients with a tumor diameter of <35 mm, which was the median tumor size of the entire group, was 94%, while it was 89% for patients having a tumor diameter of >35 mm (P = 0.128). Conclusion: Tumor size was not a risk factor predicting recurrence in patients with stage I or II endometrioid-type endometrial cancer who had lymphadenectomy.

Prognostic factors and oncological outcomes of ovarian yolk sac tumors: a retrospective multicentric analysis of 99 cases.

PURPOSE: To investigate the clinico-pathological prognostic factors and treatment outcomes in patients with ovarian yolk sac tumors (YST). METHODS: A multicenter, retrospective department database review was performed to identify patients with ovarian YST who underwent surgery between 2000 and 2017 at seven Gynecologic Oncology Centers in Turkey. RESULTS: The study group consisted of 99 consecutive patients with a mean age of 23.9 years. While 52 patients had early stage (stage I-II) disease, the remaining 47 patients had advanced stage (stage III-IV) disease. The uterus was preserved in 74 (74.8%) of the cases. The absence of gross residual disease following surgery was achieved in 76.8% of the cases. Of the 54 patients with lymph node dissection (LND), lymph node metastasis was detected in 10 (18.5%) patients. Of the 99 patients, only 3 patients did not receive adjuvant therapy, and most of the patients (91.9%) received BEP (bleomycin, etoposide, cisplatin) chemotherapy. Disease recurred in 21 (21.2%) patients. The 5-year disease-free survival (DFS) and overall survival (OS) in the entire cohort were 79.2% and 81.3%, respectively. In multivariate analysis, only residual disease following initial surgery was found to be significantly associated with DFS and OS in patients with ovarian YST (p = 0.026 and p = 0.001, respectively). CONCLUSIONS: Our results demonstrate the significance of achieving no visible residual disease in patients with ovarian YST. Fertility-sparing approach for patients with no visible residual disease affected neither DFS nor OS. Although high lymphatic involvement rate was detected, the benefit of LND could not be demonstrated.

Effect of Adjuvant Therapy on Oncologic Outcomes of Surgically Confirmed Stage I Uterine Carcinosarcoma: a Turkish Gynecologic Oncology Study

Background: Uterine carcinosarcoma is rare neoplasm that mostly presents as metastatic disease. Stage is one of the most important prognostic factor, however, the management of the early stage uterine carcinosarcoma is still controversial. Aims: To evaluate prognostic factors, treatment options, and survival outcomes in patients with surgically approved stage I uterine carcinosarcoma. Study Design: Cross-sectional study. Methods: Data of 278 patients with uterine carcinosarcoma obtained from four gynecologic oncology centers were reviewed, and 70 patients with approved stage I uterine carcinosarcoma after comprehensive staging surgery were studied. Results: The median age of the entire cohort was 65 years (range; 39-82). All patients underwent both pelvic and paraaortic lymphadenectomy. Forty-one patients received adjuvant therapy. The median follow-up time was 24 months (range; 1-129). Nineteen (27.1%) patients had disease failure. The 3-year disease-free survival and cancer-specific survival of the entire cohort was 67% and 86%, respectively. In the univariate analysis, only age was significantly associated with disease-free survival (p=0.022). There was no statistical significance for disease-free survival between observation and receiving any type of adjuvant therapy following staging surgery. Advanced age (<75 vs ≥75 years) was the only independent prognostic factor for recurrence (hazard ratio: 3.8, 95% CI=1.10-13.14, p=0.035) in multivariate analysis. None of the factors were significantly associated with cancer-specific survival. Conclusion: Advanced age was the only independent factor for disease-free survival in stage I uterine carcinosarcoma. Performing any adjuvant therapy following comprehensive lymphadenectomy was not related to the improved survival of the stage I disease.

Evaluation of trace elements associated with antioxidant enzymes in blood of primary epithelial ovarian cancer patients.

Epithelial ovarian cancer (EOC) has been associated with oxidative stress (OS) due to epithelial inflammation which makes ovaries more vulnerable to the deleterious effects of reactive oxygen species (ROS). However, antioxidant enzymes (AOEs) such as manganese-superoxide dismutase (Mn-SOD), copper,zinc-superoxide dismutase (Cu,Zn-SOD) and glutathione peroxidase (GPx1) protect cells against the biological damage of ROS-induced OS and support cancer prevention by maintaining normal cell cycle progression, inhibiting proliferation, tumor invasion, angiogenesis, inflammation or inducing apoptosis. In the present study, we aimed to measure the levels of trace elements [manganese (Mn), copper (Cu), zinc (Zn) and selenium (Se)] which are structurally and/or functionally associated with the AOEs by inductively coupled plasma/mass-spectrometry (ICP/MS) in blood samples of patients with EOC (M, n = 26) and compare the data with healthy subjects (C, n = 46). Serous EOC (M1, n = 18) data were also evaluated according to the tumor grading [well or moderately well differentiated (G 1-2) vs. poorly differentiated or undifferentiated (G3)] and staging of disease [stage I-II (SI-II) vs. stage III (SIII)]. We obtained; i) The Mn and Se levels of M were significantly lower than C, ii) only Mn levels were changed [(G3(Mn) < G 1-2 (Mn)] in M1, iii) significant correlations were observed between [Cu and Zn levels (r = 0.701, p = 0.036) in G 1-2 and (r = 0.686, p = 0.041) in G3; Cu and Se levels (r = 0.960, p = 0.000) in G3; Mn levels and Mn-SOD expression (r = 0.551, p = 0.006) in M, (r = 0.857, p = 0.007) in G 1-2 and (r = 0.690, p = 0.056) in G3; Se levels and erythrocyte GPx1 activity (r = 0.660, p = 0.053) in G 1-2 ; Se levels and erythrocyte Cu,Zn-SOD activity (r = 0.693, p = 0.038) in G3]. The study revealed that trace elements, particularly low Mn and Se levels along with high Cu/Se ratios might be of value in all histologic subtypes of EOC. Although Mn level was important in terms of discriminating tumor grades, positive correlation between Cu-Se levels was also remarkable in patients with G 1-2 tumors of M1. Moreover, high erythrocyte Cu/Se ratios might be a favourable marker for EOC.

Assessment of oxidant-antioxidant status alterations with tumor biomarkers and reproductive system hormones in uterine MYOMAS.

OBJECTIVES: Uterine myomas (UM) are responsible for significant morbidity and have adverse effects on quality of life in women. Reactive oxygen species (ROS) and antioxidant enzymes (AOE), as well as sex steroids play important roles in the reproductive physiology processes. Thus, we aimed to investigate the role of oxidant-antioxidant status in UM by measuring the AOE activities and lipid peroxidation (LPO) levels. This is the first study assessing these parameters together in UM based on also menopausal status and evaluating possible correlations between AOE activities, LPO markers, tumor biomarkers, female reproductive system hormone levels, comprehensively. STUDY DESIGN: The study group consisted of patients who have undergone surgical resection with confirmed pathology of uterine myoma (UM, n = 25) and divided into subgroups; premenopausal (UMpre) and postmenopausal (UMpost). Erythrocyte copper-zinc superoxide dismutase (Cu,Zn-SOD), catalase (CAT), glutathione peroxidase (GPx1) activities were measured along with plasma malondialdehyde (MDA) and urinary 8-epi-prostaglandin F2α (8-epi-PGF2α) levels in patients with UM. The obtained data were compared to the data of healthy individuals (C, n = 25) and its subgroups; premenopausal (Cpre) and postmenopausal (Cpost). RESULTS: All AOE activities were higher (∼40% for Cu,Zn-SOD, p = 0.003; ∼55% for CAT, p = 0.001; ∼15% for GPx1, p = 0.169) and the LPO levels were lower (∼60% for MDA, p = 0.011 and ∼45% for 8-epi-PGF2α, p = 0.055) in patients with UM vs control. Approximately similar alterations were observed in UMpre vs Cpre and in UMpost vs Cpost. A significant negative correlation between erythrocyte Cu,Zn-SOD activity and plasma MDA levels (r = -0.431, p = 0.005) was reported. CONCLUSION: Decreased LPO levels might be the consequence of compensator high antioxidant enzyme activities against mild oxidative stress in the circulation of patients with UM. The marked negative correlation between erythrocyte Cu,Zn-SOD activity and plasma MDA levels also supported this finding.

Comparison of Mayo and Milwaukee Risk Stratification Models for Predicting Lymph Node Metastasis in Endometrial Cancer.

OBJECTIVE: The aim of this study was to compare Mayo and Milwaukee risk stratification models for predicting lymphatic dissemination in patients with endometrial cancer (EC). METHODS: A total of 904 patients with EC underwent surgical treatment between 2004 and 2016 at Hacettepe University Hospital, and clinicopathological data of patients were retrieved from the computerized database of the Hacettepe University. Patients who did not undergo lymphadenectomy and who had nonendometrioid histology, stage-IV disease, and synchronous epithelial ovarian and EC were excluded. All slides of the cases were reviewed by the same gynecologic pathology subspecialist. RESULTS: The study group consisted of 307 consecutive patients with a mean age of 59.4 years (range, 26-86 years). Lymph node metastasis was detected in 28 subjects (9.1%). Primary tumor diameter, depth of myometrial invasion, lymphovascular space invasion, and cervical stromal and glandular involvement were associated with lymph node metastasis. Patients with low-risk histological features based on Mayo risk stratification system in our study group had a 0% rate of lymph node positivity. However, of the 28 patients with lymph node metastasis, 3 (10.7%) had low-risk features based on Milwaukee model. The sensitivity, specificity, false negative rate (FNR) and false positive rate of Mayo and Milwaukee risk stratification models for predicting lymphatic dissemination among women with endometrioid EC were 100%, 27.3%, 0%, and 72.7%; and 89.3%, 61.3%, 10.7%, and 38.7%, respectively. CONCLUSIONS: Although Milwaukee risk stratification model had a lower false positive rate and can decrease the number of lymphadenectomies, FNR of this new model was found as 10.7% in the present study. Furthermore, we found that Mayo model had a lower FNR and higher sensitivity. Therefore, Mayo model still looks more beneficial to predict lymph node metastasis in patients with endometrioid EC and Milwaukee risk stratification model still requires external validation.

The Clinicopathological Study of 21 Cases With Uterine Smooth Muscle Tumors of Uncertain Malignant Potential: Centralized Review Can Purify the Diagnosis.

OBJECTIVE: The objective of this study was to investigate the clinicopathological features and factors associated with recurrence in patients with uterine smooth muscle tumor of uncertain malignant potential (STUMP). METHODS: Forty-six cases diagnosed between 2000 and 2014 from 2 tertiary centers underwent blind slide review. Initial diagnosis included smooth muscle tumors with equivocal diagnosis, STUMPs, and cases that were named as leiomyosarcomas (LMS) or low-grade LMS despite not fulfilling the Stanford criteria. RESULTS: In total, 21 patients with a final diagnosis of STUMP were available. Fifteen (68.1%) of 22 patients with an initial diagnosis of STUMP, 4 (22.2%) of 18 cases with an equivocal smooth muscle tumor diagnosis, and 2 (33.3%) of 6 cases with an initial diagnosis of LMS were interpreted as STUMP after slide review. The mean age at diagnosis was 43 years (range, 20-64 years). The mean follow-up time was 65.9 months (range, 10-154 months). Four patients (19.0%) developed recurrent disease. Recurrent tumors were LMS in 3 patients (75%). One patient (4.8%) with recurrence succumbed to disease. There was no difference in patients' age (P = 1.0) or type of initial surgery (uterus conserving versus hysterectomy) (P = 0.57) between patients who recurred and did not recur. CONCLUSIONS: Uterine STUMPs can harbor significant uncertainty regarding the original diagnosis and clinical outcomes. Recurred cases may have an aggressive clinical course associated with multiple relapses and death. Uterine mesenchymal tumors other than ordinary myomas and overt sarcomas deserve a second opinion in centers with experience because the real diagnosis may vary significantly.

Oncological Outcomes of Stage II Endometrial Cancer: A Retrospective Analysis of 250 Cases.

OBJECTIVE: The aim of this study was to investigate the effect of different surgical approaches, adjuvant therapy, and pathological characteristics on oncological outcomes in patients with 2009 International Federation of Gynecology and Obstetrics (FIGO) stage II endometrial cancer (EC). METHODS: A multicenter, retrospective department database review was performed to identify patients with FIGO 2009 stage II EC who underwent surgical staging between 2002 and 2015 at 5 gynecologic oncology centers in Turkey. RESULTS: Original pathology reports of 4867 patients who underwent surgical treatment for EC were analyzed. The study group consisted of 250 FIGO stage II patients. Of these patients, 203 (81.2%) had endometrioid and 47 (18.8%) had nonendometrioid histologic subtype of EC. Whereas 199 patients (79.6%) underwent type I hysterectomy, the remaining 51 patients (20.4%) underwent radical hysterectomy. Of the 250 patients, 208 patients (83.2%) had adjuvant therapy including radiotherapy (pelvic external beam radiotherapy and/or vaginal brachytherapy [VBT]) and/or platinum-based chemotherapy. Disease recurred in 29 patients (11.6%). The 5-year disease-free survival (DFS) and overall survival (OS) for the entire cohort were 82% and 85%, respectively. Multivariate analysis showed that only adjuvant treatment (P = 0.001; hazard ratio, 4.02; 95% confidence interval, 1.72-9.36) was significantly associated with DFS. According to multivariate analysis, only age older than 60 years (P = 0.01; hazard ratio, 3.03; 95% confidence interval, 1.3-7.04) was identified as an independent risk factor for OS. However, there were no differences in OS when evaluated by grade, histology, tumor size, type of hysterectomy, or adjuvant treatment. CONCLUSIONS: In stage II EC, adjuvant external beam radiotherapy ± VBT were associated with increased DFS but not OS. However, the benefit of VBT alone on DFS could not be demonstrated. Only age was an independent risk factor for OS. Type of hysterectomy and histologic subtype of the tumor for patients with uterus-confined disease improved neither DFS nor OS in our study group.

Histological Follow-Up in Patients with Atypical Glandular Cells on Pap Smears.

CONTEXT: Atypical glandular cells (AGCs) result in the Papanicolaou (Pap) smear may be associated with significant genital and nongenital neoplastic processes. AIMS: To evaluate the underlying histopathology in women who had AGCs on Pap smears. SETTINGS AND DESIGN: Retrospective cross-sectional study. PATIENTS AND METHODS: Clinicopathological data of patients who had AGC on Pap smears and underwent histological workup between January 2004 and December 2014 were retrieved from the computerized database of a tertiary care center. Patients with a prior history of cervical intraepithelial neoplasia or gynecological cancer were excluded. STATISTICAL ANALYSIS USED: Chi-square test or Fisher's exact tests were used as appropriate. RESULTS: Cytological examination of the uterine cervix was carried out in 117,560 patients. We identified 107 patients (0.09%) with AGC and 80 of those with histological follow-up were included in the study. The median age at diagnosis was 47 years (range, 18-79), and 32 women (40%) were postmenopausal, while 56 (70%) had gynecological symptoms. Significant preinvasive or invasive lesions on pathological examination were detected in 27 (33.8%) patients, including 12 endometrial adenocarcinomas (15%), 8 cervical carcinomas (10%), 3 cervical intraepithelial neoplasia II/III (3.75%), 2 ovarian adenocarcinomas (2.5%), and 2 metastatic tumors (2.5%). Univariate analysis showed that postmenopausal status (P < 0.001), age >50 years old (P < 0.001), having symptoms at the time of admission (P = 0.041), and AGC "favor neoplasia" smear results (P = 0.041) were the clinical factors associated with significant pathological outcome. CONCLUSIONS: Patients with AGC on Pap smears should be evaluated vigilantly with histological workup, especially if they are postmenopausal or symptomatic.

Retroperitoneal nodal metastasis in primary adult type granulosa cell tumor of the ovary: Can routine lymphadenectomy be omitted?

OBJECTIVE: To investigate the incidence of retroperitoneal lymph node metastasis among patients with primary adult type granulosa cell tumor (AGCT) of the ovary. STUDY DESIGN: Between January 1982 and February 2017, patients with a pathological diagnosis of AGCT were identified. Clinical and pathological data were obtained from database records. RESULTS: A total of 151 patients with primary AGCT were identified with a mean age of 47.8 years (range, 17-91 years). 98 patients (64.9%) had stage IA, 24 (15.9%) had stage IC, 4 (2.6%) had stage IIB, 2 (1.3%) had stage IIIB, 6 (4.0%) had stage IIIC disease according to International Federation of Gynecology and Obstetrics (FIGO) 1988 criteria. In the remaining 17 patients (11.3%), primary stage was not detected. In 134 (88.7%) patients, pelvic and para-aortic lymphadenectomy was performed at primary staging surgery depending on the frozen section analysis or at re-staging surgery following initial diagnosis. In these patients, six (4.5%) of them had pelvic or paraaortic lymph node metastasis. The median number of lymph nodes removed was 43 (range, 10-96 lymph nodes). CONCLUSION: Lymph node metastasis in initially staged AGCT is rare. Routine pelvic and paraaortic lymph node dissection may be omitted in these patients.

Vaginal Reconstruction for Vaginal Obliteration Secondary to Stevens Johnson Syndrome: A Case Report and Review of Literature.

Stevens-Johnson syndrome (SJS) is a rare and acute life-threatening condition, which is almost always precipitated by drugs. Genital mucositis in female patients may also be an important cause of long-term morbidity secondary to mucosal scarring. We present the case of a 33-year-old nulligravid woman with distal vaginal synechiae necessitating a surgical approach, which occurred after an episode of SJS. Also, we aimed to review the literature to reveal cases which required surgical management for long-term genital sequelae as well as discuss preventive measures.

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

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

Impaired antioxidant enzyme functions with increased lipid peroxidation in epithelial ovarian cancer.

We aimed to identify the possible role of oxidant-antioxidant status in epithelial ovarian cancer (EOC) by measuring (a) antioxidant enzyme (AOE) activities [total superoxide dismutase (SODtotal ), manganese-SOD (Mn-SOD), copper,zinc-SOD (Cu,Zn-SOD), catalase (CAT) and glutathione peroxidase (GPx1)], (b) Mn-SOD protein expression, (c) lipid peroxidation markers [malondialdehyde (MDA), 8-epi-prostaglandin-F2α (8-epi-PGF2α)] and by evaluating the possible correlations between tumor biomarkers, reproductive hormone levels and all measured parameters, comprehensively. The data obtained from the patients with EOC (M, n = 26) evaluated according to the histopathological/clinical characteristics of tumors and compared with data of healthy controls [Ctissue (C1) and Cblood/urine (C2), n = 30, respectively). Significantly, low activities of tumor SODtotal (52%), Mn-SOD (42%), Cu,Zn-SOD (55%); high activities of tumor and erythrocyte CAT (66%, 33% respectively) and tumor GPx1 (60%); high levels of tumor Mn-SOD protein expression; tumor MDA (193%) and urinary 8-epi-PGF2α (179%) were observed in serous EOC tumors (M1, n = 18) compared with controls (P < 0.05). However, higher levels of tumor MDA, Mn-SOD protein expression and urinary 8-epi-PGF2α were observed along with lower tumor CAT activity in poorly differentiated or undifferentiated (grade 3, G 3) versus well or moderately well differentiated (grade 1-2, G 1-2) serous EOC tumors. Obtained data indicate the presence of a severe redox imbalance in EOC and draw attention to the criticial role of AOEs in the pathogenesis of the disease. © 2017 IUBMB Life, 69(10):802-813, 2017.

Impact of adjuvant treatment on oncologic outcomes in patients with stage I leiomyosarcoma of the uterus.

BACKGROUND/AIM: This study aimed to evaluate the role of adjuvant therapy for stage I uterine leiomyosarcoma (LMS). MATERIALS AND METHODS: Clinicopathological data of cases of stage I uterine LMS from 1998 to 2015 were retrieved from the computerized database of Hacettepe University Hospital. The Kaplan-Meier method was used to estimate survival and progression-free survival, and survival differences were analyzed by log-rank test. Cox regression analysis was performed to account for the potential influence of confounding factors. RESULTS: We evaluated the outcomes of 35 patients with histologically proven stage I LMS. The median age at diagnosis was 50 years. All patients underwent surgical treatment and 20 patients (57.1%) received adjuvant therapy. Twelve of these patients (34.3%) received adjuvant chemotherapy, 3 (8.6%) received adjuvant pelvic irradiation, and 5 (14.2%) received adjuvant chemotherapy with pelvic irradiation. The median follow-up duration was 34 months (range: 3-231 months). Twenty-three (65.7%) patients had a recurrence during follow-up. Adjuvant therapy did not significantly improve median progression-free survival or median overall survival. Cox regression analysis did not demonstrate any significant impact of the factors studied, including age, menopausal status, tumor size, mitotic count, staging surgery, or adjuvant therapy. CONCLUSION: Adjuvant therapy for surgically treated stage I uterine LMS did not improve oncologic outcomes.