Publications by authors named "Kunter Yuce"

75 Publications

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

Taiwan J Obstet Gynecol 2020 Nov;59(6):862-864

Hacettepe University, Department of Gynecology and Obstetrics, Division of Gynecologic Oncology, Ankara, Turkey.

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.
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http://dx.doi.org/10.1016/j.tjog.2020.09.012DOI Listing
November 2020

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

Gynecol Oncol 2020 07 30;158(1):105-111. Epub 2020 Apr 30.

General Directorate of Public Health, Ministry of Health of Turkey, Ankara, Turkey.

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.
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http://dx.doi.org/10.1016/j.ygyno.2020.04.698DOI Listing
July 2020

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

J Obstet Gynaecol 2021 Apr 29;41(3):414-420. Epub 2020 Apr 29.

Department of Radiation Oncology, Hacettepe University Medical School, Ankara, Turkey.

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 statement 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. 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. 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.
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http://dx.doi.org/10.1080/01443615.2020.1737661DOI Listing
April 2021

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

Int J Gynecol Cancer 2020 01 1;30(1):35-40. Epub 2019 Dec 1.

Obstetrics and Gynecology, Hacettepe University, Faculty of Medicine, Ankara, Turkey.

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.
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http://dx.doi.org/10.1136/ijgc-2019-000932DOI Listing
January 2020

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

Turk J Med Sci 2019 Oct 24;49(5):1403-1410. Epub 2019 Oct 24.

Gynecologic Oncology Clinic, Etlik Zübeyde Hanım Women’s Health Teaching and Research Hospital,University of Health Sciences, Ankara, Turkey

Background/aim: We aimed to define the effect of tumor size on recurrence and survival rates in patients with stage I–II 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: 3–335 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.
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http://dx.doi.org/10.3906/sag-1902-224DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7018323PMC
October 2019

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

Arch Gynecol Obstet 2019 07 13;300(1):175-182. Epub 2019 Apr 13.

Division of Gynecologic Oncology, Etlik Zubeyde Hanim Women's Health Teaching and Research Hospital, Etlik, 06010, Ankara, Turkey.

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.
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http://dx.doi.org/10.1007/s00404-019-05160-6DOI Listing
July 2019

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

Balkan Med J 2019 07 15;36(4):229-234. Epub 2019 Mar 15.

Department of Gynecologic Oncology, Hacettepe University Faculty of Medicine, Ankara, Turkey

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.
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http://dx.doi.org/10.4274/balkanmedj.galenos.2019.2018.12.75DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6636652PMC
July 2019

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

J Trace Elem Med Biol 2019 Mar 16;52:254-262. Epub 2019 Jan 16.

Hacettepe University, Faculty of Medicine, Department of Obstetrics and Gynecology, Ankara 06100, Turkey. Electronic address:

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 < G 1-2 ] 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.
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http://dx.doi.org/10.1016/j.jtemb.2019.01.010DOI Listing
March 2019

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

Eur J Obstet Gynecol Reprod Biol 2018 Oct 1;229:1-7. Epub 2018 Aug 1.

Hacettepe University, Faculty of Pharmacy, Department of Toxicology, Ankara 06100, Turkey; Lokman Hekim University, Faculty of Pharmacy, Department of Toxicology, Ankara, Turkey. Electronic address:

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 (UM) and postmenopausal (UM). 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 (C) and postmenopausal (C).

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 UM vs C and in UM vs C 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.
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http://dx.doi.org/10.1016/j.ejogrb.2018.07.031DOI Listing
October 2018

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

Int J Gynecol Cancer 2018 06;28(5):869-874

Department of Obstetrics and Gynecology, Faculty of Medicine, Hacettepe University, Ankara, Turkey.

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.
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http://dx.doi.org/10.1097/IGC.0000000000001261DOI Listing
June 2018

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

Int J Gynecol Cancer 2018 02;28(2):233-240

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.
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http://dx.doi.org/10.1097/IGC.0000000000001178DOI Listing
February 2018

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

J Cytol 2017 Oct-Dec;34(4):203-207

Department of Obstetrics and Gynecology, Division of Gynecologic Oncology, Hacettpe University, Faculty of Medicine, Ankara, Turkey.

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 ( < 0.001), age >50 years old ( < 0.001), having symptoms at the time of admission ( = 0.041), and AGC "favor neoplasia" smear results ( = 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.
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http://dx.doi.org/10.4103/JOC.JOC_209_16DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5655657PMC
November 2017

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

Eur J Obstet Gynecol Reprod Biol 2017 Dec 9;219:70-73. Epub 2017 Oct 9.

Department of Obstetrics and Gynecology, Division of Gynecologic Oncology, Faculty of Medicine, Hacettepe University, Ankara, Turkey.

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.
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http://dx.doi.org/10.1016/j.ejogrb.2017.10.010DOI Listing
December 2017

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

Oman Med J 2017 Sep;32(5):436-439

Departments of Obstetrics and Gynecology, Gynecologic Oncology Unit, Hacettepe University Faculty of Medicine, Ankara, Turkey.

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.
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http://dx.doi.org/10.5001/omj.2017.82DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5632693PMC
September 2017

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

Int J Gynecol Cancer 2018 01;28(1):161-167

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.
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http://dx.doi.org/10.1097/IGC.0000000000001133DOI Listing
January 2018

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

IUBMB Life 2017 10 8;69(10):802-813. Epub 2017 Sep 8.

Department of Toxicology, Faculty of Pharmacy, Hacettepe University, Ankara, Turkey.

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 (SOD ), 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 [C (C1) and C (C2), n = 30, respectively). Significantly, low activities of tumor SOD (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.
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http://dx.doi.org/10.1002/iub.1675DOI Listing
October 2017

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

Arch Gynecol Obstet 2017 Nov 2;296(5):979-987. Epub 2017 Sep 2.

Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, Faculty of Medicine, Hacettepe University, Ankara, Turkey.

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.
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http://dx.doi.org/10.1007/s00404-017-4496-4DOI Listing
November 2017

Factors associated with survival after relapse in patients with low-risk endometrial cancer treated with surgery alone.

J Gynecol Oncol 2017 Sep 16;28(5):e65. Epub 2017 Jun 16.

Department of Gynecologic Oncology, Tepecik Education and Research Hospital, Faculty of Medicine, University of Health Sciences, Izmir, Turkey.

Objective: To determine factors influencing overall survival following recurrence (OSFR) in women with low-risk endometrial cancer (EC) treated with surgery alone.

Methods: A multicenter, retrospective department database review was performed to identify patients with recurrent "low-risk EC" (patients having less than 50% myometrial invasion [MMI] with grade 1 or 2 endometrioid EC) at 10 gynecologic oncology centers in Turkey. Demographic, clinicopathological, and survival data were collected.

Results: We identified 67 patients who developed recurrence of their EC after initially being diagnosed and treated for low-risk EC. For the entire study cohort, the median time to recurrence (TTR) was 23 months (95% confidence interval [CI]=11.5-34.5; standard error [SE]=5.8) and the median OSFR was 59 months (95% CI=12.7-105.2; SE=23.5). We observed 32 (47.8%) isolated vaginal recurrences, 6 (9%) nodal failures, 19 (28.4%) peritoneal failures, and 10 (14.9%) hematogenous disseminations. Overall, 45 relapses (67.2%) were loco-regional whereas 22 (32.8%) were extrapelvic. According to the Gynecologic Oncology Group (GOG) Trial-99, 7 (10.4%) out of 67 women with recurrent low-risk EC were qualified as high-intermediate risk (HIR). The 5-year OSFR rate was significantly higher for patients with TTR ≥36 months compared to those with TTR <36 months (74.3% compared to 33%, p=0.001). On multivariate analysis for OSFR, TTR <36 months (hazard ratio [HR]=8.46; 95% CI=1.65-43.36; p=0.010) and presence of HIR criteria (HR=4.62; 95% CI=1.69-12.58; p=0.003) were significant predictors.

Conclusion: Low-risk EC patients recurring earlier than 36 months and those carrying HIR criteria seem more likely to succumb to their tumors after recurrence.
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http://dx.doi.org/10.3802/jgo.2017.28.e65DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5540724PMC
September 2017

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

Turk J Med Sci 2017 Jun 12;47(3):841-846. Epub 2017 Jun 12.

Department of Obstetrics and Gynecology, Division of Gynecologic Oncology, Faculty of Medicine, Hacettepe University, Ankara, Turkey.

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.
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http://dx.doi.org/10.3906/sag-1603-135DOI Listing
June 2017

Prognostic factors and treatment outcomes in surgically-staged non-invasive uterine clear cell carcinoma: a Turkish Gynecologic Oncology Group study.

J Gynecol Oncol 2017 Jul;28(4):e49

Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, Faculty of Medicine, Baskent University, Ankara, Turkey.

Objective: To assess the prognosis of surgically-staged non-invasive uterine clear cell carcinoma (UCCC), and to determine the role of adjuvant therapy.

Methods: A multicenter, retrospective department database review was performed to identify patients with UCCC who underwent surgical treatment between 1997 and 2016 at 8 Gynecologic Oncology Centers. Demographic, clinicopathological, and survival data were collected.

Results: A total of 232 women with UCCC were identified. Of these, 53 (22.8%) had surgically-staged non-invasive UCCC. Twelve patients (22.6%) were upstaged at surgical assessment, including a 5.6% rate of lymphatic dissemination (3/53). Of those, 1 had stage IIIA, 1 had stage IIIC1, 1 had stage IIIC2, and 9 had stage IVB disease. Of the 9 women with stage IVB disease, 5 had isolated omental involvement indicating omentum as the most common metastatic site. UCCC limited only to the endometrium with no extra-uterine disease was confirmed in 41 women (73.3%) after surgical staging. Of those, 13 women (32%) were observed without adjuvant treatment whereas 28 patients (68%) underwent adjuvant therapy. The 5-year disease-free survival rates for patients with and without adjuvant treatment were 100.0% vs. 74.1%, respectively (p=0.060).

Conclusion: Extra-uterine disease may occur in the absence of myometrial invasion (MMI), therefore comprehensive surgical staging including omentectomy should be the standard of care for women with UCCC regardless of the depth of MMI. Larger cohorts are needed in order to clarify the necessity of adjuvant treatment for women with UCCC truly confined to the endometrium.
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http://dx.doi.org/10.3802/jgo.2017.28.e49DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5447148PMC
July 2017

Stage IIIC transitional cell carcinoma and serous carcinoma of the ovary have similar outcomes when treated with platinum-based chemotherapy.

J Turk Ger Gynecol Assoc 2017 Mar;18(1):33-37

Department of Obstetrics and Gynecology, Division of Gynecologic Oncology, Hacettepe University Faculty of Medicine, Ankara, Turkey.

Objective: Previous studies reported better outcomes for transitional cell carcinoma (TCC) of the ovary when compared with more common histologic types such as serous epithelial ovarian cancers (EOCs). The aim of this study was to compare the survival outcomes of platinum- based chemotherapy in patients with stage IIIC TCCs and serous EOCs.

Material And Methods: Clinicopathologic features and survival data of patients with FIGO stage IIIC TCC and serous EOC who had undergone primary surgery followed by six cycles of intravenous platinum/taxane between 2007 and 2015 were retrieved from the database of Hacettepe University Hospital.

Results: We identified 14 (10.9%) TCCs and 114 (89.1%) serous EOCs. The median follow-up duration was 28 months (range, 3-101 months). Univariate analysis revealed that the TCCs and serous EOCs had similar progression-free survival (PFS) and overall survival (OS). Patients with residual disease less than 1 cm had longer OS than patients with residual disease greater than 1 cm (75.0 vs. 45.0 months, p=0.012). Cox regression analysis of all potential prognostic factors showed that the only independent prognostic factor significantly associated with OS was residual disease less than 1 cm [hazard ratio=0.38; 95% confidence interval: (0.19-0.77); p=0.007].

Conclusion: Surgically treated advanced stage TCCs did not have a significantly better prognosis after platinum/taxane-based chemotherapy when compared with serous EOCs. Residual tumor volume after primary surgery was the only independent predictor of OS in patients with EOC. Our results demonstrate the significance of achieving optimal cytoreduction in all histologic subtypes of EOC.
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http://dx.doi.org/10.4274/jtgga.2016.0190DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5450208PMC
March 2017

HPV types and E6/E7 mRNA expression in cervical samples from Turkish women with abnormal cytology in Ankara, Turkey.

Turk J Med Sci 2017 Feb 27;47(1):194-200. Epub 2017 Feb 27.

Department of Medical Microbiology, Virology Unit, Faculty of Medicine, Hacettepe University, Ankara, Turkey.

Background/aim: Human papillomaviruses have been established as a risk factor for invasive carcinoma of the uterine cervix. HPV E6/E7 oncogene expression has recently emerged as a promising biomarker to determine the risk for progression to high-grade cervical lesions. The aim of this study was to evaluate HPV mRNA and DNA detection in samples with abnormal cytology.

Materials And Methods: Cervical specimens were obtained at the Department of Obstetrics and Gynecology via cervical brushes during January-October 2011. Liquid-based cytology slides were evaluated according to the 2001 Bethesda System. Cytology specimens from a total of 81 women with abnormal cytology were included. Real-time PCR and NASBA assays were performed to detect HPV DNA and E6/E7 mRNA, respectively.

Results: HPV DNA was identified in 73 samples (90.1%). HPV E6/E7 mRNA expression was observed in 45 samples (55.6%). A statistically significant difference was observed among cytological diagnosis groups. In 25 patients, a biopsy was performed during the follow-up. HPV DNA was detected in all of these patients. HPV E6/E7 expression was present only in CIN I-III diagnosed patients.

Conclusion: The E6/E7 mRNA test is a robust indicator of cytological atypia and correlates better with progressive lesions than DNA assays.
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http://dx.doi.org/10.3906/sag-1508-155DOI Listing
February 2017

Incidence of Lymph Node Metastasis in Surgically Staged FIGO IA G1/G2 Endometrial Cancer With a Tumor Size of More Than 2 cm.

Int J Gynecol Cancer 2017 03;27(3):486-492

*Department of Obstetrics and Gynecology, Division of Gynecologic Oncology, Faculty of Medicine, and †Department of Obstetrics and Gynecology, Faculty of Medicine, Hacettepe University, Ankara, Turkey.

Objective: The study aims to investigate effect of tumor size on lymphatic spread in patients with low-risk endometrial cancer (EC).

Methods: This study included patients with EC who underwent staging surgery with systematic lymphadenectomy between 2002 and 2015 at the Hacettepe University Hospital. Patients with grade 1 or 2 endometrioid type tumor who had 50% or lower myometrial invasion were included. Patients who had no myometrial invasion or had uterine high-risk features (nonendometrioid histology, grade 3, and deep myometrial invasion) were excluded.

Results: The study group consisted of 191 patients, and the mean age of the patients was 57.8 years. Of these patients, 124 (64.9%) had tumor size of more than 2 cm and 67 (35.1%) had tumor size of 2 cm or less. Lymph node metastasis was detected in 12 (9.7%) of the 124 patients with tumor size of more than 2 cm. On the other hand, none of the 67 patients (0%) with tumor size of 2 cm or less was found to have lymphatic involvement. Of the factors analyzed for correlation with lymph node metastasis in patients with low-risk EC, the presence of lymphovascular space invasion (LVSI) and primary tumor size were found to be significant predictors of lymphatic spread in univariate analysis (P < 0.001 and P = 0.009, respectively). In multivariate analysis, tumor size (odds ratio, 6.86; 95% confidence interval, 1.007-infinite; P < 0.05) and LVSI (odds ratio, 14.261; 95% confidence interval, 3.4-59.6; P < 0.001) were 2 independent predictors associated with lymphatic involvement.

Conclusions: Our trial supports that tumor size of more than 2 cm and LVSI are 2 independent factors for lymph node metastasis in patients with low-risk EC. Both factors can be used together to select patients with traditional low-risk histologic features who would absolutely benefit from lymph node dissection.
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http://dx.doi.org/10.1097/IGC.0000000000000919DOI Listing
March 2017

Does Preoperative Diagnosis of Endometrial Hyperplasia Necessitate Intraoperative Frozen Section Consultation?

Balkan Med J 2016 Nov 1;33(6):657-661. Epub 2016 Nov 1.

Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, Hacettepe University School of Medicine, Ankara, Turkey.

Background: In women with endometrial hyperplasia, there is a risk for co-existent endometrial cancer when patients are subjected to immediate surgical treatment.

Aims: The aim of this study was to investigate the frequency of endometrial cancer and the accuracy of frozen section analysis at the time of hysterectomy among patients with endometrial hyperplasia, to reveal whether or not a preoperative diagnosis of endometrial hyperplasia necessitates frozen section consultation.

Study Design: Retrospective cross-sectional study.

Methods: A department database review was performed to identify patients who were subjected to hysterectomy with a preoperative diagnosis of endometrial hyperplasia, during the period from 2007 to 2014.

Results: The study group included 189 cases. The final pathological examination revealed endometrial cancer in 16 women (8.4%). The risk of cancer in patients with endometrial hyperplasia was 1 of 125 (0.8%) in simple hyperplasia without atypia, 1 of 21 (4.8%) in complex hyperplasia without atypia and 14 of 43 (32.5%) in atypical hyperplasia. Of women with cancer, 2 of 16 (12.5%) had high-risk features. Frozen section analysis was requested in 46 cases. Frozen sections helped to identify six out of 11 cases of endometrial cancer (54.5%). The sensitivity, specificity and positive and negative predictive values of frozen section analysis for the detection of endometrial cancer among women with endometrial hyperplasia were 54.4%, 97.2%, 85.7% and 87.5%, respectively.

Conclusion: Although a significant proportion of patients with atypical endometrial hyperplasia are diagnosed with endometrial cancer following hysterectomy, most of these cases have low-risk features and do not require surgical staging. Additionally, intraoperative frozen section analysis if not helpful for diagnosing concurrent endometrial cancer in patients with endometrial hyperplasia. Therefore, it seems that patients with endometrial hyperplasia can be operated upon in settings with no available method for obtaining frozen sections intraoperatively.
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http://dx.doi.org/10.5152/balkanmedj.2016.151232DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5156449PMC
November 2016

Extrauterine Spread, Adjuvant Treatment, and Prognosis in Noninvasive Uterine Papillary Serous Carcinoma of the Endometrium: A Retrospective Multicenter Study.

Int J Gynecol Cancer 2017 01;27(1):102-108

*Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, Faculty of Medicine, Hacettepe University; †Division of Gynecologic Oncology, Etlik Zubeyde Hanim Women's Health Teaching and Research Hospital, Kecioren; ‡Department of Gynecologic Oncology, Zekai Tahir Burak Women's Health, Education and Research Hospital; §Department of Obstetrics and Gynecology, Faculty of Medicine, Hacettepe University, Ankara; and ∥Department of Gynecologic Oncology, Tepecik Education and Research Hospital, Izmir, Turkey.

Objectives: The aim of this retrospective multicenter study was to investigate the frequency of extrauterine metastasis and to evaluate the importance of surgical staging and adjuvant treatment among patients with noninvasive uterine papillary serous carcinoma (UPSC) of the endometrium.

Materials And Methods: A multicenter, retrospective department database review was performed to identify patients with UPSC of the endometrium who underwent surgical staging between 2000 and 2015 at 4 Gynecologic Oncology Centers in Turkey. Demographic, clinicopathological, and survival data were collected.

Results: A total of 182 patients with primary UPSC of the endometrium were identified. Of these, 33 (18.1%) had tumors limited to the endometrium with no myometrial invasion. Twenty (60.6%) of these 33 patients had no extrauterine involvement and International Federation of Gynecology and Obstetrics 2009 stage 1A disease was diagnosed after complete staging. The remaining 13 (39.4%) patients had disease beyond the uterine corpus including 5 with omental, 3 with adnexal, 1 with cervical stromal involvement, 1 with disease in the pelvic lymph nodes, and 1 with isolated para-aortic lymph node metastasis. Two patients had metastases in more than one location including omentum/adnexa/pelvic-para-aortic lymph nodes and omentum/pelvic-para-aortic lymph nodes, respectively. Of the 20 patients with disease confined to the endometrium, 6 (30%) patients received adjuvant treatment.

Conclusions: Noninvasive UPSC has a high tendency for extrauterine spread and omentum is the most commonly involved location. Therefore, comprehensive surgical staging including omentectomy and pelvic-para-aortic lymph node dissection is mandatory in this group of patients. Risk of extrauterine spread is significantly associated with the presence of lymphovascular space invasion, elevated preoperative CA 125 levels, and positive peritoneal cytology. Adjuvant therapy for women with endometrium-confined disease improves neither progression-free survival nor overall survival.
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http://dx.doi.org/10.1097/IGC.0000000000000838DOI Listing
January 2017

Clinical and pathological characteristics related to parametrial involvement in clinical early-stage cervical cancer.

Ginekol Pol 2016 ;87(6):417-21

Department of Obstetrics and Gynecology, Faculty of Medicine, Hacettepe University, Ankara, Turkey.

Objectives: Since parametrial involvement is believed to be a crucial factor in the management of cervical cancer, our study was designed to investigate the clinical and pathological features which predicted parametrial involvement in patients with clinical early-stage cervical cancer.

Material And Methods: The study included patients with clinical early-stage cervical cancer who underwent radical hys-terectomy with pelvic and para-aortic lymphadenectomy between December 2001 and August 2014, at the Hacettepe University Hospital. The clinical and pathological characteristics of the affected patients were evaluated, including age, histologic subtype, tumor size, depth of cervical stromal invasion, lympho-vascular space invasion (LVSI), and lymph node metastasis. Univariate and multivariate analyses were performed to reveal factors associated with parametrial involvement.

Results: The study group consisted of 126 patients (mean age: 52.7 years; range: 29-83), including 101 (80.2%) with squamous, 19 (15.1%) with adenocarcinoma, and 6 (4.8%) with adenosquamous histological subtype of cervical cancer. Parametrial involvement and lymph node metastasis were detected in 41 (32.5%) and 46 (36.5%) women, respectively. Univariate analysis showed that deep cervical stromal invasion, LVSI, tumor size > 2 cm and lymph node metastasis were associated with parametrial involvement. Multivariate logistic regression analysis identified the independent risk factors associated with parametrial involvement as LVSI (OR 8.93, 95% CI 1.1-73.5, p = 0.042) and lymph node metastasis (OR 8.8, 95% CI 1.5-9.3, p = 0.004).

Conclusions: LVSI, deep cervical stromal invasion, lymph node metastasis and tumor size are significantly associated with parametrial involvement in patients with clinical early-stage cervical cancer.
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http://dx.doi.org/10.5603/GP.2016.0018DOI Listing
July 2018

Assessment of Cervicovaginal Cancer Antigen 125 Levels: A Preliminary Study for Endometrial Cancer Screening.

Gynecol Obstet Invest 2016 13;81(6):518-522. Epub 2016 Feb 13.

Department of Obstetrics and Gynecology, Hacettepe University School of Medicine, Ankara, Turkey.

Aim: We primarily aimed to compare the levels of serum and cervicovaginal cancer antigen 125 (CA 125) in women with and without endometrial carcinoma in order to reveal whether cervicovaginal CA 125 could be used as a non-invasive method.

Methods: A preliminary case-control study was designed. The study group consisted of patients who were operated for endometrial adenocarcinoma or endometrial intraepithelial neoplasia. The control group consisted of patients who underwent surgery for benign gynecological diseases. Serum and cervicovaginal secretions were immediately collected before surgery to compare levels of CA 125.

Results: The mean cervicovaginal CA 125 levels in patients with endometrial cancer and controls were 1,598.1 ± 1,691.1 versus 947.0 ± 1,282.7 U/ml, respectively (p = 0.016). Whereas area under receiver operating characteristic curve was 0.62 for serum CA 125, it was 0.68 for cervicovaginal CA 125. The optimal threshold of CA 125 in cervicovaginal secretion was calculated to be 575 U/ml, which detected endometrial precancer or cancer with sensitivity of 78% and specificity of 57%. The positive and negative predictive values for this threshold were 38.7 and 88.2%, respectively.

Conclusion: In conclusion, detection of CA 125 in cervicovaginal secretion has a potential role for the non-invasive screening of endometrial precancers and cancers.
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http://dx.doi.org/10.1159/000444321DOI Listing
April 2017

Radical Hysterectomy and Total Abdominal Vaginectomy for Primary Vaginal Cancer.

Int J Gynecol Cancer 2016 Mar;26(3):580-1

Department of Obstetrics and Gynecology, Division of Gynecologic Oncology, Faculty of Medicine, Hacettepe University, Ankara, Turkey; and Department of Obstetrics and Gynecology, Faculty of Medicine, Hacettepe University, Ankara, Turkey.

The aim of this surgical video is to demonstrate en bloc radical removal of uterus and vagina in a patient with clinical early-stage vaginal cancer. Surgical treatment was offered to our patient for clinical early-stage primary vaginal cancer. An en bloc radical hysterectomy, systematic pelvic lymphadenectomy, and total abdominal vaginectomy were performed. Postoperative adjuvant radiation or chemotherapy was not recommended for completely resected pathologic stage I disease with no lymph node involvement and negative surgical margins. Radical surgery can be a treatment option for selected patients with primary vaginal cancer.
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http://dx.doi.org/10.1097/IGC.0000000000000636DOI Listing
March 2016

The Role of Frozen-Section in the Surgical Management of Patients with Endometrial Intraepithelial Neoplasia.

Turk Patoloji Derg 2015 ;31(3):181-7

Department of Obstetrics and Gynaecology, Hacettepe University Faculty of Medicine, ANKARA, TURKEY.

Objective: Patients with endometrial intraepithelial neoplasia may have concurrent endometrial cancer if managed surgically or develop cancer in time if managed conservatively. Therefore, intraoperative assessment of the uterus may be helpful if a surgical approach is decided on. Our study aimed to investigate the role of frozen-section examination in patients with endometrial intraepithelial neoplasia.

Material And Method: Patients with endometrial intraepithelial neoplasia who were subjected to hysterectomy with intraoperative frozen-section assessment were included. Main outcome measures were the rates of concurrent endometrial cancer and concurrent high-risk endometrial cancer as well as the efficacy of frozen-section in the detection of concurrent invasive disease and in the designation of low-risk and high-risk features.

Results: The study group consisted of seventy-three patients. Permanent pathology revealed endometrial adenocarcinoma in 19.2% whereas only one patient (1.4%) had high-risk disease necessitating surgical staging. Frozen-section diagnoses were consistent with final pathology in 93.2% of patients in terms of the presence or absence of co-existent carcinoma. When frozen-section reports were further evaluated in terms of the presence or absence of high-risk endometrial carcinoma, consistency with the final pathology was seen in 98.6% of patients.

Conclusion: Co-existent endometrial cancer is not uncommon in endometrial intraepithelial neoplasia. Intraoperative frozen-section evaluation should therefore be considered whenever possible. Frozen-section is effective in the detection of coexistent invasive disease and in the designation of low-risk features. Although coexistent high-risk cancer is extremely rare, frozen-section assessment is not successful in determining high-risk features. Therefore, a re-staging surgery may be required on rare occasions.
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http://dx.doi.org/10.5146/tjpath.2015.01328DOI Listing
October 2016

Intraoperative Ex Vivo High-Resolution Sonography: A Novel Technique for the Assessment of Myometrial Invasion in Endometrial Cancer.

Int J Gynecol Cancer 2015 Nov;25(9):1639-44

From the *Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, †Department of Radiology, and ‡Department of Pathology, Faculty of Medicine, Hacettepe University, Ankara, Turkey.

Objective: This study aims to assess the diagnostic performance of a novel intraoperative ex vivo ultrasonography technique in determining deep myometrial invasion (MI) in patients with apparently low-risk endometrial cancer (EC).

Methods: This prospective study included patients with type I EC who underwent staging laparotomy at Hacettepe University Hospital from December 2011 to September 2014. After hysterectomy, a radiologist with special training in gynecology examined the uterus ex vivo using a 12-MHz superficial linear probe. The specimen was sent for intraoperative frozen section (FS) analysis. The results were compared with permanent section reports.

Results: In total, 45 female patients were eligible for analysis. Intraoperative ex vivo high-resolution sonography (IEVHS) correctly assessed depth of MI in 39 of 45 cases (86.6%) and overestimated it in 5 cases (11.1%). Only 1 case with deep infiltration was underestimated by IEVHS as invasion of less than one half of the myometrium. Frozen section correctly identified depth of MI in 41 of 46 cases (91.1%), overestimated it in 1 case (2.2%), and underestimated it in 3 cases (6.6%). The sensitivity, specificity, positive predictive value, and negative predictive value of IEVHS and FS for assessment of deep MI were 87.5%, 86.4%, 58.3%, and 96.9%, and 62.5%, 97.3%, 83.3%, and 92.3%, respectively.

Conclusions: Intraoperative ex vivo high-resolution sonography is a novel technique for assessing MI in EC. Its high sensitivity for deep MI could be useful as an adjunct to FS (enabling pathologists to obtain targeted FS slices) and could improve the accuracy of FS.
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http://dx.doi.org/10.1097/IGC.0000000000000531DOI Listing
November 2015