Tayfun Toptas

Total Laparoscopic Versus Open Radical Hysterectomy in Stage IA2–IB1 Cervical Cancer: Disease Recurrence and Survival Comparison

BACKGROUND Few reports have examined the impact of laparoscopic approach on survival outcomes in patients with early-stage (IA2-IB1) cervical cancer (CC). In this study we aimed to compare disease recurrence and survival outcomes of total laparoscopic radical hysterectomy (TLRH) with those for open radical hysterectomy (ORH) and pelvic lymphadenectomy in patients with early-stage CC. PATIENTS AND METHODS A single-center, retrospective analysis was conducted in a total of 68 patients who treated with TLRH (n=22) or ORH (n=46) between 2007 and 2010. The primary endpoint of the study was progression-free survival (PFS). RESULTS Median follow-up time was 42.50 months (range, 38.40-55.42 months) for the TLRH group and 43.50 months (range, 37.66-52.65) for the ORH group. The study groups were comparable in terms of baseline characteristics except the ORH group had more patients with tumor size greater than 2 cm (P=.026), depth of stromal invasion greater than 33% (P<.0001), and International Federation of Gynecology and Obstetrics stage IB1 disease (P=.019). However, these factors had no impact on overall and PFS in Cox regression analyses. In total, three recurrences were observed in the TLRH group. Two of the 3 patients were alive with no evidence of disease, and the remaining individual was alive with disease (AWD). In the ORH group, 5 patients had recurrences. Two of the 5 patients died of disease, and three were AWD. The estimated 3-year PFS (86.1% versus 90.6%, respectively; P=.32) and overall survival (100% vs. 95.4%, respectively; P=.82) were comparable in the TLRH and ORH groups. CONCLUSIONS TLRH and ORH have similar survival outcomes in patients with early-stage CC.

Analysis of Metastatic Regional Lymph Node Locations and Predictors of Para-aortic Lymph Node Involvement in Endometrial Cancer Patients at Risk for Lymphatic Dissemination.

Objective The aim of this study was to provide detailed knowledge of the metastatic lymph node (LN) locations and to determine factors predicting para-aortic LN metastasis in endometrial cancer patients at risk (intermediate/high) for LN involvement. Methods A prospective case series with planned data collection was conducted in a total of 173 patients who treated with systematic pelvic para-aortic lymphadenectomy up to the renal vessels. All the LNs removed from pelvic and para-aortic basins—low or high according to the level of the inferior mesenteric artery—were evaluated separately. Logistic regression analyses were performed to determine the impact of variables on para-aortic metastasis. Results Lymph node metastasis was observed in 21.9% of the patients, pelvic LN involvement in 17.9%, para-aortic LN involvement in 15.0%, both pelvic and para-aortic LN involvement in 10.9%, and isolated para-aortic LN involvement in 4.0%. The most common metastatic LN locations were the external iliac (50.0%), obturator (50.0%), and low precaval regions (36.8%). The least common location of metastasis was the high precaval region (5.3%). Among patients with para-aortic LN metastasis, 42.3% had metastasis above the inferior mesenteric artery. The number of metastatic pelvic LNs greater than or equal to 2 was the only independent predictor of para-aortic metastasis in multivariate analysis (odds ratio, 23.38; 95% confidence interval, 1.35-403.99; P = 0.030), with 96.94% sensitivity, 95.87% specificity, 98.6% positive predictive value, and 97.0% negative predictive value. Conclusions The current study supports the idea that in patients at risk of LN involvement, the systematic lymphadenectomy should be performed up to the renal vessels due to the high rate of upper level involvement.

Prognostic Significance of Retroperitoneal Lymphadenectomy, Preoperative Neutrophil Lymphocyte Ratio and Platelet Lymphocyte Ratio in Primary Fallopian Tube Carcinoma: A Multicenter Study

Purpose The purpose of this study is to evaluate the prognostic role of preoperative neutrophil to lymphocyte ratio (NLR) and platelet to lymphocyte ratio (PLR) and the need for para-aortic lymphadectomy in patients with primary fallopian tube carcinoma (PFTC). Materials and Methods Ninety-one patients with a diagnosis of PFTC were identified through the gynecologic oncology service database of six academic centers. Clinicopathological, surgical, and complete blood count data were collected. Results In univariate analysis, advanced stage, suboptimal surgery, and NLR > 2.7 were significant prognostic factors for progression-free survival, whereas in multivariate analysis, only advanced stage and suboptimal surgery were significant. In addition, in univariate analysis, cancer antigen 125 ≥ 35 U/mL, ascites, advanced stage, suboptimal surgery, NLR > 2.7, PLR > 233.3, platelet count ≥ 400,000 cells/mm3, staging type, and histological subtype were significant prognostic factors for overall survival (OS); however, in multivariate analysis, only advanced stage, suboptimal surgery, NLR > 2.7, and staging type were significant. Inclusion of pelvic and para-aortic lymphadenectomy in surgery showed significant association with longer OS, with a mean and median OS of 42.0 months and 35.5 months (range, 22 to 78 months), respectively, vs. 33.5 months and 27.5 months (range, 14 to 76 months), respectively, for patients who underwent surgery without para-aortic lymphadenectomy (hazard ratio, 3.1; 95% confidence interval, 1.4 to 5.7; p=0.002). Conclusion NLR (in both univariate and multivariate analysis) and PLR (only in univariate analysis) were prognostic factors in PFTC. NLR and PLR are inexpensive and easy tests to perform. In addition, patients with PFTC who underwent bilateral pelvic and para-aortic lymphadenectomy had longer OS.

Assessment of circulating betatrophin concentrations in lean glucose-tolerant women with polycystic ovary syndrome

Abstract The aims of the current study were to investigate the betatrophin levels in lean glucose-tolerant women with polycystic ovary syndrome (PCOS), and to explore the relationships between these levels and antropometric, hormonal and metabolic parameters. The study population consisted of 50 lean (body mass index [BMI] < 25 kg/m2) women diagnosed with PCOS using the Rotterdam criteria, and 60 age- and BMI-matched healthy controls without any features of clinical or biochemical hyperandrogenism. Before recruitment, glucose tolerance was evaluated in all of the subjects using the 2-h 75 g oral glucose-tolerance test, and only those exhibiting normal glucose tolerance were enrolled. Serum betatrophin levels were significantly higher in women with PCOS (median 322.3; range 44.7–1989.3 ng/L) compared to the controls (median 199.9; range 6.2–1912.9 ng/L; p = .005). In the control group, no significant correlation was evident between betatrophin levels and clinical or biochemical parameters. In the PCOS group, betatrophin levels were positively correlated with prolactin levels (r = .286, p = .046) and negatively correlated with BMI (r = −.283, p = .049), waist/hip ratio (r = −.324, p = .023), and low-density lipoprotein cholesterol levels (r = −.385, p = .006). Impact statement What is already known on this subject: Several studies have suggested that primary alteration in beta-cell function is a pathophysiological feature of PCOS, and insulin resistance is the most significant predictor of beta-cell dysfunction independent of obesity. Betatrophin is a circulating protein that is primarily expressed in the liver in humans. Early experimental investigations demonstrated that overexpression of betatrophin significantly promoted pancreatic beta-cell proliferation, insulin production and improved glucose tolerance. Few studies have investigated the association between PCOS and betatrophin. However, in contrast to our study, the authors included overweight/obese patients and glucose tolerance was not evaluated before recruitment. What the results of this study add: Our results showed that serum betatrophin levels were significantly higher in lean glucose-tolerant PCOS women than in age- and BMI-matched healthy controls. What are the implications of these findings for clinical practice and/or further research: Elevated betatrophin levels in PCOS women, in the absence of obesity and glucose intolerance, may reflect a compensatory mechanism in order to counteract metabolic syndrome-related risk factors.

Survival analysis of pelvic lymphadenectomy alone versus combined pelvic and para-aortic lymphadenectomy in patients exhibiting endometrioid type endometrial cancer

The therapeutic benefit of lymphadenectomy in patients exhibiting endometrial cancer (EC) remains controversial. The aim of the present study was to determine whether the addition of para-aortic lymphadenectomy to pelvic lymphadenectomy (PLND) improves survival in patients with endometrioid type EC. A single tertiary-center, retrospective analysis was conducted in a total of 186 patients who were surgically treated with either PLND alone (n=97) or combined pelvic and para-aortic lymphadenectomy (PPaLND; n=89). Adjuvant treatments were assigned according to the Gynecologic Oncology Group (GOG) risk of recurrence analysis. The primary endpoint of the present study was progression-free survival (PFS). The median follow-up time was 38 months (95% confidence interval, 36.47–42.90) for all patients. No statistically significant differences were identified between the two groups in terms of overall survival (OS), PFS or time to progression (TTP). Kaplan-Meier estimates of three-year OS, PFS and TTP for patients with low or low-intermediate risk were as follows: PLND, 100, 98.7 and 98.7%, respectively; and PPaLND, all 100%. The estimated three-year OS, PFS and TTP for patients with high or high-intermediate risk were as follows: PLND, 92.3, 81.3 and 81.3%; and PPaLND, 90.7, 77.1 and 80.9%, respectively. No statistically significant differences were detected in the three-year OS, PFS and TTP between the lymphadenectomy groups, regardless of the GOG risk of recurrence (PLND, 98.4, 95.3 and 95.3%; and PPaLND, 94.9, 87.1 and 89.4%). Therefore, the combination treatment, PPaLND did not provide any survival advantage over pelvic lymphadenectomy alone.

Comparison of intravaginal progesterone gel and intramuscular 17‑α‑hydroxyprogesterone caproate in luteal phase support

The main objective of this study was to compare the pregnancy rates of intramuscular (IM) 17-α-hydroxyprogesterone caproate (17-HPC) and intravaginal (IV) progesterone gel administration in in vitro fertilization-embryo transfer (IVF-ET) cycles. The IM 17-HPC and IV progesterone groups included 632 (66.4%) and 320 (33.6%) women undergoing the first cycles of IVF-ET treatment, respectively. Multivariate analyses annotated for all potential confounders showed that the use of IV progesterone retained a predictive value for the total β-human chorionic gonadotropin (hCG) positivity and clinical pregnancy rates [adjusted odds ratio (OR), 1.97; 95% confidence interval (CI), 1.28–3.03; P=0.002; and OR, 1.66; 95% CI, 1.07–2.60; P=0.03, respectively]. However, biochemical and on-going pregnancy rates did not differ significantly between the groups (OR, 1.85; 95% CI, 1.00–3.41; P=0.05; and OR, 1.43, 95% CI, 0.89–2.30; P=0.14, respectively). Luteal phase support (LPS) with IV progesterone gel in comparison with IM 17-HPC appears to be associated with higher clinical pregnancy rates in IVF-ET cycles. However, this benefit is clinically irrelevant in terms of on-going pregnancy outcomes.

Immunohistochemical Analysis of E-Cadherin, p53 and Inhibin-α Expression in Hydatidiform Mole and Hydropic Abortion

The purpose of this study was to investigate the role of E-cadherin, p53, and inhibin-α immunostaining in the differential diagnosis of hydropic abortion (HA), partial hydatidiform mole (PHM), and complete hydatidiform mole (CHM). E-cadherin, p53, and inhibin-α protein expression patterns were investigated immunohistochemically using paraffin -embedded tissue sections from histologically diagnosed cases of HA (n = 23), PHM (n = 24), and CHM (n = 23). Expression patterns of these markers were scored semi-quantitatively according to the staining intensity, percentage of positive cells, and immunoreactivity score. Classification of cases was established on histologic criteria and supported by the molecular genotyping. Immunostaining allowed the identification of specific cell types with E-cadherin, p53, and inhibin-α expression in all cases. E-cadherin expression was detected on the cell surface of villous cytotrophoblasts. We observed a marked decline in the expression of E-cadherin from HAs to PHMs to CHMs. The p53-positive reaction was restricted to the nucleus of villous cytotrophoblasts. Significantly increased p53 expression was observed in CHMs, compared with HAs and PHMs. The expression of inhibin-α was localised in the cytoplasm of villous syncytiotrophoblasts, and the expression of this marker was significantly higher in PHMs and CHMs than HAs. In conclusion, immunohistochemical analysis of E-cadherin, p53, and inhibin-α expression could serve as a useful adjunct to conventional methods in the differential diagnosis of HA, PHM, and CHM.

The clinical impact of serous tubal intraepithelial carcinoma on outcomes of patients with high-grade serous carcinoma of the ovary, fallopian tube, and peritoneum

Aims: To investigate whether the presence of serous tubal intraepithelial carcinoma (STIC) is associated with clinical outcomes in a nonselected (unknown BRCA status) cohort of patients with a high-grade serous carcinoma (HGSC) of the ovary, fallopian tube, and peritoneum. Settings and Design: A prospective case-series with planned data collection. Subjects and Methods: The study was conducted in a total of 131 patients, who underwent primary cytoreductive surgery between 2007 and 2012. Histological examination of the fallopian tubes included the “sectioning and extensively examining the fimbriated end” protocol. The diagnosis of STIC was based on the combination of morphology and immunohistochemistry. The patients were divided into two groups according to the absence or presence of STIC and compared clinicopathologically. Statistical Analysis Used: Analyses were performed using PASW 18 (SPSS/IBM, Chicago, IL, USA) software. The primary outcome was progression-free survival (PFS), and the secondary outcome was overall survival (OS). Results: STIC was identified in 20.6% of patients. Median follow-up time was 49.5 months for the STIC-positive group and 38.0 months for the STIC-negative group. Study groups were comparable in terms of clinicopathological characteristics with the exception that patients with STIC had less lymph node involvement (55.0% vs. 65.4%, P = 0.001), and more diagnosis of primary tubal carcinoma (29.6% vs. 3.8%, P = 0.001) compared to those without STIC. No statistically significant differences in terms of PFS (P = 0.462) and OS (P = 0.501) were observed between the groups. Conclusions: The absolute identification of the origin of tumor cell does not seem to significantly affect the clinical course of the patients with HGSC.

Is routine ECC necessary in patients with HPV16 and normal cytology

In the present study, we primarily aimed to correlate the colposcopy results of patients with human papillomavirus (HPV) positivity and abnormal cervical screening results. Secondarily, we attempted to define the role of endocervical curettage (ECC) in the colposcopic evaluation of patients who had normal cytology and HPV16, which is the most carcinogenic HPV type.

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

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