The serum steroid signature of PCOS hints at the involvement of novel pathways for excess androgen biosynthesis.

CONTEXT Polycystic ovary syndrome (PCOS) is defined by androgen excess and ovarian dysfunction in the absence of a specific physiological diagnosis. The best clinical marker of androgen excess is hirsutism, while the best biochemical parameter is still a matter of debate. Current consensus guidelines recommend, among other hormones, serum free testosterone as an important serum parameter to measure androgen excess. Recently, however, novel active androgens and androgen metabolic pathways have been discovered. OBJECTIVE To assess the contribution of novel androgens and related steroid biosynthetic pathways to the serum steroid pool in PCOS women in comparison to healthy controls. DESIGN This is a case control study, wherein PCOS was diagnosed according to the AE-PCOS 2009 criteria. Serum steroid profiling was performed by liquid chromatography high-resolution mass spectrometry. SETTING Yeditepe University and associated clinics in Istanbul, Turkey, together with Bern University Hospital Inselspital, Bern, Switzerland. PARTICIPANTS 42 PCOS women and 42 matched, healthy control women. MAIN OUTCOME MEASURES Assessment of 34 steroids compartmentalized in four androgen related pathways: the classic androgen pathway, the backdoor pathway, the C11-oxy backdoor pathway, and the C11-oxy (11β-hydroxyandrostenedione) pathway. RESULTS Metabolites of all four pathways were identified in healthy and PCOS women. Highest concentrations were found for progesterone in controls and androstenedione in PCOS. Lowest levels were found for 11-ketotestosterone in controls compared to PCOS, and for 20α-hydroxyprogesterone in PCOS compared to controls. PCOS also had higher serum testosterone levels compared to the controls. PCOS women had overall higher levels of steroid metabolites of all four androgen pathways compared to healthy controls. CONCLUSIONS Novel alternative pathways contribute to the androgen production in healthy and PCOS women. Hyperandrogenism in PCOS is characterized by an overall increase of serum androgens in the classic, backdoor and C11-oxy pathways. While monogenetic disorders of steroid biosynthesis can be recognized by a specific pattern in the steroid profile, no diagnostic pattern or classifier was found in the serum for PCOS

The Effect of Dehydroepiandrosterone on Ovarian Reserve in Ovarian Damage Caused by Methotrexate

To determine the possible detrimental effects of multiple methotrexate doses has on the ovarian reserve and to determine the beneficial effects of dehydroepiandrosterone supplementation. The rats (n:24) divided into three groups; Group 1: control group, Group 2: dehydroepiandrosterone and methotrexate group (6mg/kg dehydroepiandrosterone dissolved in 0.1 ml sesame seed oil subcutaneously for ten days and 1mg/kg intramuscular methotrexate at the 1st, 3rd, 5th and 7th days) and Group 3: methotrexate group (1mg/kg intramuscular methotrexate at the 1st, 3rd, 5th and 7th day). The groups compared in regards to their histopathological ovarian damage scores and AMH values. It established that multiple methotrexate applications had a considerable effect on reducing vascular congestion in the ovarian tissue. Both in groups 2 and 3 AMH values found to be significantly lower. When this decline in the ovarian reserve examined comparatively; while both the group 2 and 3 reported having a considerable and continuous reduction in the AMH levels correlative to the control group; the primordial, primary and total follicle counts shown to stay statistically the same in the group 2 (

The Effects of Leukocyte- and Platelet-Rich Plasma (L-Prp) and Pure Platelet-Rich Plasma (P-Prp) in a Rat Endometriosis Model

Objective: We aimed to investigate the effect of platelet‑rich plasma (PRP) derivatives, which can be produced from the patient’s blood and have minimal side effects, on endometriosis.Methods: To our knowledge, this is the first study in the literature that studies the relationship between PRP and endometriosis. Endometriosis foci were created in the first operation. In the second operation (30th day), four groups were formed wherein group 1 (n = 8) was administered saline, group 2 (n = 7) leukocyte and platelet‑rich plasma (L‑PRP), group 3 (n = 8) pure platelet‑rich plasma (P‑PRP) and group 4 (n = 10) was used to obtain PRP. In the last operation (60th day), the endometriotic foci was measured and then excised.Findings: There was no statistically significant difference between the pre and post volumes of the endometriotic foci, between their volume differences, and volume difference rates (P > 0.05). However, it was observed that existing implant volumes in all groups decreased statistically significantly within their groups by the end of the experiment compared to the previous volumes (P < 0.05).Conclusion: When the implants were assessed through histopathological scoring in terms of edema, vascular congestion, inflammatory cell  infiltration, hemorrhage, epithelial line, and hemosiderin accumulation, and immunohistochemical staining was assessed in terms of VEGF, there was no significant difference in the comparison between the groups. Although L‑PRP and P‑PRP generated more reduction in the endometriosis foci, they did not create any statistical differences. Key words: L‑Prp; P‑Prp; VEGF; endometriosis

INVESTIGATION OF THE SUPERIORITY OF TDxFML AND LAMELLAR BODY COUNTS IN THE EVALUATION OF FETAL LUNG MATURATION

Objective: To evaluate the superiority of the most performed tests; lamellar body counts and TDxFLM test compared to each other to estimate the maturation of fetal lungs and also to evaluate the reasons for the unclear cut-off values of lamellar body counts. Material and Method: Amnion fluids that were taken into 2 separate tubes from 56 patients within a year were evaluated with both of the tests. Newborns were evaluated and monitored for respiratory distress syndrome of newborns by a neonatologist who was blinded to the results of the amnion fluids. Clinical findings such as grunting, tachypnea, retractions and cyanosis beginning within 6-8 hours after birth, oxygen need over 24 hours, arterial blood gas analyses with partial oxygen pressure under 50 mmHg and presence of chest x-ray findings that are compatible with the situation were accepted as the respiratory distress of newborns. Results: Respiratory distress was not seen in 44 of the 56 newborns while it was seen in 12 (21.4%) of them. In 30 patients whose lamellar body counts were > 55000/mm(3) without centrifuge, RDS was not seen. In the patients whose lamellar body counts were 41, all cases can be detected. Conclusion: Count of lamellar bodies is adiagnostic tool which is fast, practical, easily accessible and cost-effective; also there is no doubt on the benefits of the tool. It seems that the different cut-off values have reasonable causes. Thus, we suggest that every clinic should have its own cut-off values. In the presence of interim results, additional evaluation with TDxFLM was found to increase the sensitivity and specificity.WOS:00040990730000

Effect of adjuvant chemotherapy in stage III cervical cancer patients treated with concurrent chemoradiation: A multicenter study

INTRODUCTION: A significant proportion of cervical cancer (CC) patients are diagnosed at a locally advanced stage. Concurrent chemoradiotherapy (CCRT) is the cornerstone of treatment for patients with locally advanced CC. However, the role of adjuvant chemotherapy (AC) after CCRT is controversial. In this study, we analyzed the efficacy of AC after CCRT in stage III CC patients. METHODS: We performed a multicenter, retrospective analysis of 139 International Federation of Gynecology and Obstetrics stage III CC patients treated with CCRT of whom 45.3% received AC. Our goal was to determine the impact of AC on survival in these patients. RESULTS: Five-year progression-free survival (PFS) was 37.5% and 16% in patients receiving CCRT with and without AC, respectively (p = 0.008). Median PFS was 30.9 months (CI 95% 14.8-46.9) and 16.6 months (CI 95% 9.3-23.9) in patients receiving CCRT with and without AC, respectively. Five-year overall survival (OS) was 78.2% and 28.4% in patients receiving CCRT with and without AC, respectively (p < 0.001). Median OS was 132.2 months (CI 95, %66.5-197.8) and 34.9 months (CI 95% 23.1-46.7) in patients receiving CCRT with and without AC, respectively. CONCLUSION: Our study suggests that AC provides OS and PFS benefit in stage III CC patients. Larger studies are needed to identify subgroups of patients who would benefit from AC

Efficacy and safety of folfiri plus aflibercept in second-line treatment of metastatic colorectal cancer: Real-life data from Turkish oncology group

Aims: The addition of aflibercept to the fluorouracil and irinotecan (FOLFIRI) regimen significantly improved clinical outcomes in patients with metastatic colorectal cancer (CRC) previously treated with oxaliplatin. We aimed to investigate the efficacy and safety of second-line FOLFIRI and aflibercept combination in patients with metastatic CRC in real-life experience. Materials and Methods: Four hundred and thirty-three patients who treated with FOLFIRI and aflibercept in the second-line were included in the study. The clinical and pathological features of the patients were recorded retrospectively. Survival (overall and progression-free survival [PFS]), response rates, and safety data were analyzed. Results: The median age was 61. Majority of patients (87.5%) received first-line bevacizumab and 10.1% of patients received anti-epidermal growth factor receptor agents. About 80% of patients had KRAS, 18.6% of patients had NRAS, and 6.4% of patients had BRAF mutations. The median OS was 11.6 months (95% confidence interval [CI], 10.6-12.6) and the median PFS was 6 months (95% CI, 5.5-6.5). About 4.6% of patients had complete response and 30.6% of patients had partial response as best tumor response. Grade 1-2 toxicities were seen in 33.4% of patients, while grade 3-4 toxicities were recorded in 27% of patients. Eight patients (2%) died due to treatment toxicity. Conclusions: Overall and PFS were similar in routine clinical practice compared to phase III pivotal VELOUR trial. However, response rates were found to be higher. It was observed that there were fewer adverse events compared to the VELOUR trial

Real-world data on efficacy and safety of first-line alectinib treatment in advanced-stage, ALK-positive non-small-cell lung cancer patients: A Turkish Oncology Group study

Aims: In this multicenter study, the authors aimed to determine the real-life efficacy and safety of first-line alectinib. Materials & methods: This retrospective trial included advanced-stage, ALK-positive non-small-cell lung cancer patients who were treated with first-line alectinib in terms of ALK-tyrosine kinase inhibitors, regardless of previous chemotherapy. The co-primary end points were progression-free survival both for all patients and for the treatment-naive population. The secondary end points were overall response rate, overall survival, rate of CNS progression and safety. Results & conclusion: A total of 274 patients (n = 177 for treatment-naive patients) were enrolled in the study. The median progression-free survival was 26 and 28.8 months for all patients and the treatment-naive group, respectively. The overall response rate, CNS progression rate and 1-year overall survival ratio were 77.9, 12.4 and 77%. Alectinib is a highly effective therapy with a favorable safety profile