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.

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.

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.

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.

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.

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.

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.

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

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.

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

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.

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.

Radical Hysterectomy and Total Abdominal Vaginectomy for Primary Vaginal Cancer.

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.

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

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.

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

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.

Assessing the Quality of Life in Patients With Endometrial Cancer Treated With Adjuvant Radiotherapy.

OBJECTIVE: The current study evaluates long-term quality of life (QOL) and sexual function of patients with endometrial cancer who received adjuvant pelvic external beam radiotherapy (EBRT) and/or vaginal brachytherapy (BRT). MATERIALS AND METHODS: One hundred forty-four endometrial cancer survivors who were treated between January 2000 and December 2009 in our department were included in this study. Median follow-up was 79 months (range, 31-138 months). Fifty-two patients were treated with 45 to 50.4 Gy EBRT, 76 were with BRT, and 16 were with both EBRT and BRT. Brachytherapy was in the form of vaginal cuff BRT with 5 × 550 cGy high dose rate BRT, prescribed to the first 4 cm and whole wall thickness of vagina. Quality of life was assessed using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 and subscales from the supplemental 24-item Cervical Cancer Module. RESULTS: Vaginal BRT patients reported better physical functioning (P = 0.01), role functioning (P = 0.03), and sexual enjoyment (P = 0.01) compared to EBRT group. Symptom score (P = 0.01), lymphedema (P = 0.03), pain (P = 0.02), and diarrhea (P = 0.009) scores were also higher with EBRT. Vaginal BRT did not worsen symptom scores or sexual functions when added to EBRT. Obese patients experienced higher rates of lymphedema (P = 0.008). Cognitive and role functioning scores were significantly higher in patients with normal body mass index. CONCLUSIONS: External beam radiotherapy negatively affects long-term QOL and sexual functions in endometrial cancer survivors. Vaginal BRT provides higher QOL. Patients with body mass index within normal limits have improved QOL.

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

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.

Lymphovascular space involvement is the sole independent predictor of lymph node metastasis in clinical early stage endometrial cancer.

PURPOSE: To determine clinicopathological risk factors associated with lymph node metastasis in endometrial cancer (EC). METHODS: Clinicopathological data of patients who underwent comprehensive surgical staging for clinical early stage EC between 2001 and 2010 at Hacettepe University Hospital was retrospectively reviewed. RESULTS: Two hundred and sixty-one patients were included. There were 26 patients (10.0%) with lymph node metastasis. Of these, 14 (5.4%) had pelvic lymph node metastasis, 8 (3.1%) had both pelvic and paraaortic lymph node metastasis, and 4 (1.5%) had isolated paraaortic metastasis. Univariate analysis revealed tumor size >2 cm, type II cancer, grade III histology, cervical stromal invasion, deep myometrial invasion, positive peritoneal cytology, adnexal involvement, serosal involvement, and presence of lymphovascular space involvement (LVSI) as significant clinicopathological factors associated with retroperitoneal lymph node metastasis. For paraaortic metastasis either isolated or with pelvic lymph node metastasis, significant factors were grade III disease, cervical stromal invasion, deep myometrial invasion, positive peritoneal cytology, adnexal involvement, serosal involvement, pelvic lymph node metastasis, and presence of LVSI. The only factor associated with isolated paraaortic lymph node metastasis was LVSI. Multivariate analysis revealed LVSI as the only independent factor for both retroperitoneal and paraaortic lymph node metastasis (odds ratio 14.9; 95% confidence interval 3.8-59.0; p < 0.001, and odds ratio 20.9; 95% confidence interval 1.9-69.9; p = 0.013, respectively). CONCLUSION: Lymphovascular space involvement is the sole predictor of lymph node metastasis in EC. Therefore, LVSI status should be requested from the pathologist during frozen examination whenever possible to consider when a decision to perform or omit lymphadenectomy is made.

Role of postmenopausal bleeding pattern and women's age in the prediction of endometrial cancer.

BACKGROUND: Women with postmenopausal bleeding should be evaluated efficiently to exclude endometrial carcinoma. AIMS: To estimate the risk of endometrial cancer using individual case characteristics among women with postmenopausal bleeding in whom the endometrial thickness is >4 mm. METHODS: Women with postmenopausal bleeding underwent clinical evaluation followed by transvaginal ultrasonography and endometrial biopsy. Clinical evaluation included age, body mass index, duration of menopause, number of bleeding episodes and amount of bleeding. RESULTS: This study included 142 women, and endometrial carcinoma was found in 18 (12.7%). Older age, higher body mass index, longer duration of menopause, longer lasting bleeding episodes, higher amount of bleeding and recurrent bleeding episodes were the clinical characteristics associated with endometrial cancer. However, multivariate analysis revealed >55 years of age during postmenopausal bleeding, history of recurrent bleeding episodes and bleeding exceeding 5 pads per day in each episode as significant parameters, which predicted the presence of endometrial cancer among women with postmenopausal bleeding. CONCLUSIONS: Prompt evaluation is required in women with postmenopausal bleeding to exclude endometrial cancer. Transvaginal ultrasonography is a reasonable first-line approach, and invasive sampling is required when ultrasonographic endometrial thickness is above 4 mm. However, about 90% of women with postmenopausal bleeding will finally be found to have a nonmalignant condition. Therefore, women who are at increased cancer risk should further be distinguished. This may be achieved using individual patient characteristics that result in a more accurate evaluation strategy with lower rates of unnecessary invasive procedures.