Tayup Şimşek

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

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.

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

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.

Correlation of Minimum Apparent Diffusion Coefficient and Maximum Standardized Uptake Value of the Primary Tumor with Clinicopathologic Characteristics in Endometrial Cancer

Objective: To explore the correlation of the primary tumor’s maximum standardized uptake value (SUVmax) and minimum apparent diffusion coefficient (ADCmin) with clinicopathologic features, and to determine their predictive power in endometrial cancer (EC). Methods: A total of 45 patients who had undergone staging surgery after a preoperative evaluation with 18F-fluorodeoxyglucose (FDG) positron emission tomography/computerized tomography (PET/CT) and diffusion-weighted magnetic resonance imaging (DW-MRI) were included in a prospective case-series study with planned data collection. Multiple linear regression analysis was used to determine the correlations between the study variables. Results: The mean ADCmin and SUVmax values were determined as 0.72±0.22 and 16.54±8.73, respectively. A univariate analysis identified age, myometrial invasion (MI) and lymphovascular space involvement (LVSI) as the potential factors associated with ADCmin while it identified age, stage, tumor size, MI, LVSI and number of metastatic lymph nodes as the potential variables correlated to SUVmax. In multivariate analysis, on the other hand, MI was the only significant variable that correlated with ADCmin (p=0.007) and SUVmax (p=0.024). Deep MI was best predicted by an ADCmin cutoff value of ≤0.77 [93.7% sensitivity, 48.2% specificity, and 93.0% negative predictive value (NPV)] and SUVmax cutoff value of >20.5 (62.5% sensitivity, 86.2% specificity, and 81.0% NPV); however, the two diagnostic tests were not significantly different (p=0.266). Conclusion: Among clinicopathologic features, only MI was independently correlated with SUVmax and ADCmin. However, the routine use of 18F-FDG PET/CT or DW-MRI cannot be recommended at the moment due to less than ideal predictive performances of both parameters.

Prognostic risk factors for lymph node involvement in patients with endometrial cancer

Objective: We aimed to analyze variables affecting lymph node (LN) involvement and to assess the need for systematic lymphadenectomy in patients with endometrial cancer (EC). Materials and Methods: A single centre retrospective analysis was conducted in a total of 128 consecutive patients with EC who underwent systematic pelvic or combined pelvic and paraaortic lymphadenectomy between 2009 and 2012. Mann-Whitney U, chi-square, and Fisher’s exact test were used for univariate analyses when appropriate. Variables with a p value <0.05 in the univariate analysis were included into a multivariate logistic regression analysis. The effects of variables on LN involvement are reported using adjusted odds ratios (ORs) and 95% confidence intervals (CI). Results: In univariate analysis, grade 2-3, tumor size ≥3 cm, deep (≥50%) myometrial invasion, presence of cervical, adnexal or omental involvement, positive peritoneal cytology, open surgical approach (laparotomy), combined pelvic and paraaortic lymphadenectomy and number of total LNs removed (>30) were found associated with LN involvement. However, the number of total LNs removed (>30) was the only independent variable that predict LN involvement in multivariate analysis [OR: 15.08; 95% CI: (1.28-177.59); p=0.03]. Conclusion: This study demonstrates that the more LNs removed during staging of EC, the greater the probability of finding LN metastasis.

Relationships of nuclear, architectural and FIGO grading systems in endometrial cancer

Objective: To examine correlations among nuclear, architectural, and International Federation of Gynecology and Obstetrics (FIGO) grading systems, and their relationships with lymph node (LN) involvement in endometrioid endometrial cancer. Material and Methods: Histopathology slides of 135 consecutive patients were reviewed with respect to tumor grade and LN metastasis. Notable nuclear atypia was defined as grade 3 nuclei. FIGO grade was established by raising the architectural grade (AG) by one grade when the tumor was composed of cells with nuclear grade (NG) 3. Correlations between the grading systems were analyzed using Spearman’s rank correlation coefficients, and relationships of grading systems with LN involvement were assessed using logistic regression analysis. Results: Correlation analysis revealed a significant and strongly positive relationship between FIGO and architectural grading systems (r=0.885, p=0.001); however, correlations of nuclear grading with the architectural (r=0.535, p=0.165) and FIGO grading systems (r=0.589, p=0.082) were moderate and statistically non-significant. Twenty-five (18.5%) patients had LN metastasis. LN involvement rates differed significantly between tumors with AG 1 and those with AG 2, and tumors with FIGO grade 1 and those with FIGO grade 2. In contrast, although the difference in LN involvement rates failed to reach statistical significance between tumors with NG 1 and those with NG 2, it was significant between NG 2 and NG 3 (p=0.042). Although all three grading systems were associated with LN involvement in univariate analyses, an independent relationship could not be established after adjustment for other confounders in multivariate analysis. Conclusion: Nuclear grading is significantly correlated with neither architectural nor FIGO grading systems. The differences in LN involvement rates in the nuclear grading system reach significance only in the setting of tumor cells with NG 3; however, none of the grading systems was an independent predictor of LN involvement.OBJECTIVE To examine correlations among nuclear, architectural, and International Federation of Gynecology and Obstetrics (FIGO) grading systems, and their relationships with lymph node (LN) involvement in endometrioid endometrial cancer. MATERIAL AND METHODS Histopathology slides of 135 consecutive patients were reviewed with respect to tumor grade and LN metastasis. Notable nuclear atypia was defined as grade 3 nuclei. FIGO grade was established by raising the architectural grade (AG) by one grade when the tumor was composed of cells with nuclear grade (NG) 3. Correlations between the grading systems were analyzed using Spearmans rank correlation coefficients, and relationships of grading systems with LN involvement were assessed using logistic regression analysis. RESULTS Correlation analysis revealed a significant and strongly positive relationship between FIGO and architectural grading systems (r=0.885, p=0.001); however, correlations of nuclear grading with the architectural (r=0.535, p=0.165) and FIGO grading systems (r=0.589, p=0.082) were moderate and statistically non-significant. Twenty-five (18.5%) patients had LN metastasis. LN involvement rates differed significantly between tumors with AG 1 and those with AG 2, and tumors with FIGO grade 1 and those with FIGO grade 2. In contrast, although the difference in LN involvement rates failed to reach statistical significance between tumors with NG 1 and those with NG 2, it was significant between NG 2 and NG 3 (p=0.042). Although all three grading systems were associated with LN involvement in univariate analyses, an independent relationship could not be established after adjustment for other confounders in multivariate analysis. CONCLUSION Nuclear grading is significantly correlated with neither architectural nor FIGO grading systems. The differences in LN involvement rates in the nuclear grading system reach significance only in the setting of tumor cells with NG 3; however, none of the grading systems was an independent predictor of LN involvement.

Angiomyofibroblastoma of the retrorectal region: a case report

Angiomyofibroblastoma (AMFB) is a rare benign subcutaneous mesenchymal lesion. AMFB is mostly described in the vulvovaginal region with occasional cases reported in other female urogenital tract sites in women of reproductive age and early menopause, and in the male inguinoscrotal region. AMFB can clinically be misdiagnosed for Bartholin’s gland cyst or lipoma. A. 44-year-old female patient admitted firstly in December 2016 to gynecologic oncology department of Akdeniz University Medical Faculty. She had complaints of pelvic pain for the previous 8 months. A palpable, nontender solid mass lesion protruding to the left lateral wall of the vagina was observed. Bimanual examination detected a mobile mass measuring 8 x 7 cm in the retrorectal region, communicating with vagina. The patient was operated in January 2017 in collaboration with department of general surgery. Her postoperative period was uneventful, and she was discharged and future control visit was arrange. Surgical specimen appeared as an opalescent-white solid mass measuring 7 x 6 cm.Its microscopic examination revealed a well-circumscribed lesion containing spindle, and epitheloid cells. Based on histological findings, the diagnosis of angiomyofibroblastoma was made. Close postoperative follow-up was decided for the patient. Postoperative 7. month gynecologic controls of the patient did not reveal any pathologic finding. In summary, AMFB of the retrorectal region is extremely rare and is diagnostically challenging. Because of the benign behavior of AMFB with rare local recurrence, excluding other neoplasms and making the accurate diagnosis based on histological features is important.