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Background: We previously identified a panel of genes associated with outcome of ovarian cancer. The purpose of the current study was to assess whether variants in these genes correlated with ovarian cancer risk. Methods and Findings: Women with and without invasive ovarian cancer (749 cases, 1,041 controls) were genotyped at 136 single nucleotide polymorphisms (SNPs) within 13 candidate genes. Risk was estimated for each SNP and for overall variation within each gene. At the gene-level, variation within MSL1 (male-specific lethal-1 homolog) was associated with risk of serous cancer (p = 0.03); haplotypes within PRPF31 (PRP31 pre-mRNA processing factor 31 homolog) were associated with risk of invasive disease (p = 0.03). MSL1 rs7211770 was associated with decreased risk of serous disease (OR 0.81, 95% CI 0.66-0.98; p = 0.03). SNPs in MFSD7, BTN3A3, ZNF200, PTPRS, and CCND1A were inversely associated with risk (p<0.05), and there was increased risk at HEXIM1 rs1053578 (p = 0.04, OR 1.40, 95% CI 1.02-1.91). Conclusions: Tumor studies can reveal novel genes worthy of follow-up for cancer susceptibility. Here, we found that inherited markers in the gene encoding MSL1, part of a complex that modifies the histone H4, may decrease risk of invasive serous ovarian cancer. [ABSTRACT FROM AUTHOR]

Background: One needs to choose wisely between primary neoadjuvant chemotherapy and primary cytoreductive surgery in ovarian cancer. The aim was to determine the recurrence free survival and overall survival after surgery for epithelial ovarian cancer and also the risk factors for recurrence and death. Methods: Electronic medical records of 322 women operated for ovarian, fallopian or primary peritoneal cancer between 2011 and 2015 were reviewed. Descriptive statistics were used to describe patients and their clinical outcomes. Cox proportional hazard models were used for risk factor analysis. Adjusted hazard ratios were obtained for recurrence and death, adjusted for stage, primary treatment modality, residual disease and histology. Kaplan-Meier curves were drawn for probability of recurrence-free survival and overall survival. The log rank test was used to compare survival probabilities. Results: The majority were stage III or stage IV (78%), serous histology (71%) and high grade (64%). Primary cytoreduction was done in 48% and interval cytoreduction in 52%. The median duration of follow up (survival) was 77 months (95% CI 72-82). There were 179 known recurrences (55.6 %). The estimated median time to recurrence was 22 (95% CI 14.5- 29.5) months. The independent risk factors for recurrence were neoadjuvant chemotherapy [HR 2.14, 95% CI 1.48-3.09], stage III/IV [HR 2.75; 95% CI 1.40-5.41], high grade serous histology [HR 1.69; 95% CI 1.12-2.54] and sub-optimal debulking [HR 3.15, 95% CI 2.19-4.55]. There were 78 known deaths (24.2 %) with a mean time to death of 24.3 (SD 16.1) months. The independent risk factors for death were sub-optimal debulking [HR 3.07; 95% CI 1.78-5.29] and stages III and IV cancer [HR 3.07; 95% CI 1.14-8.27]. Conclusions: Most ovarian cancers recur within 2 years. Risk factors for mortality are advanced stage and sub-optimal debulking. Maximal efforts at down staging and surgical resection will increase survival. [ABSTRACT FROM AUTHOR]

Introduction: Squamous cell carcinoma antigen (SCC Ag) is a sub-fraction of the tumor antigen TA-4, first isolated by Kato and Torigoe, the most commonly used tumor marker in cervical cancer. It can be used as a serum marker to detect residual disease, early local recurrence, or distant metastasis in locally advanced cervical cancer even before the clinical symptoms of recurrence or metastasis. Methods and Materials: Between January 2018 and August 2018, 30 patients with squamous cell carcinoma cervix (FIGO) stages IB2-IVA, who received concurrent chemoradiation, followed by brachytherapy, were included in the study. Serum SCC Ag levels were collected at four time points during the course of the treatment, and their correlation with tumor and treatment factors were analyzed. Results: As the FIGO stage increases, mean pre-treatment SCC Ag also increases. Node-positive patients had higher pre-treatment SCC Ag as compared to those who were negative (P = 0.05). There was a statistically significant decreasing trend in the mean SCC Ag at the end of EBRT (P = 0.015). After completion of treatment, 78% had a complete response, 8% had a partial response, and 14% had progressive disease with statistically significant elevation of SCC Ag at 6 weeks of follow-up (P = 0.01). Patients who progressed or had the residual disease at follow-up were found to have high pre-treatment SCC Ag values. Conclusion: SCC Ag can be potentially used as a reference indicator of biological behavior of cervical cancer, to monitor the treatment response, and as a prognostic marker, especially in those with node-positive disease. [ABSTRACT FROM AUTHOR]

Introduction: Cervical cytology has limited sensitivity to detect cervical pre-cancerous lesions. High-risk human papillomavirus (hr-HPV) DNA testing has high sensitivity but its specificity is limited. This study was done to assess the utility of p16INK4a/ki-67 dual stained cytology in improving the predictive value for high-grade cervical (CIN2+) lesions. Aim/Objective: To assess the significance of P16/Ki-67 immunocytochemistry in improving the predictive value for high-grade cervical intraepithelial (≥CIN 2+) lesions on Pap smear. Material and Methods: This was a prospective diagnostic study that included 93 patients with ASC-US/LSIL/ASC-H and HSIL on thin prep cervical smears and who also underwent hr-HPV DNA test and colposcopy-guided biopsy. Biopsy was the gold standard against which the performance of P16INK4a/Ki-67 and hr-HPV results were compared. Results: In women of all ages, sensitivity of (96.8%) hr-HPV test and p16/Ki-67 dual immunocytochemistry (≥1 positive cell) were similar and negative predictive value (NPV) was (97.1% vs. 97.9%) but the latter test showed better specificity (69.4% vs. 53.2%) and positive predictive value (PPV, 61.2% vs. 50.8%) for ≥CIN 2 lesions. A higher cut off of at least 10 positive cells gives a higher specificity and PPV, with slightly decreased sensitivity and NPV. Conclusion: Because high-risk HPV test has a high sensitivity and NPV, whereas P16/Ki-67 dual immunocytochemistry (≥10 positive cells) has a high specificity and PPV, the latter can be recommended as an ancillary test in hr-HPV-positive women to reduce the number of women going for colposcopy and biopsies. [ABSTRACT FROM AUTHOR]

The global increase in cancer burden is a challenge for countries with scarce resources. Amongst all the malignancies, gynaecological cancer still continues to have a high incidence and prevalence leading to significant morbidity and mortality. While a multipronged strategy of decreasing the gynaecological cancer burden is a global priority, one of the key strategies to decrease the morbidity and mortality is to train gynaecological oncology specialists. Most of the developed nations have an established gynaecologic oncology training programme in the form of a well-designed curriculum and skill training. However, in developing countries where the actual disease burden of these cancers is highest, such focused training programmes have only started emerging and evolving over the past two decades. While it is a positive step to initiate such training programmes in a country like India, there are still gaps in the uniformity of curriculum and training. Also, exposure to modern practices in gynaecologic oncology surgery, chemotherapy and technology in radiation oncology, especially brachytherapy, is still insufficient in many centres. This review discusses some of the challenges and opportunities in the still evolving programmes for training gynaecologic oncologists in India. [ABSTRACT FROM AUTHOR]

Objective: To investigate the inhibitory effect of tadalafil on the contractility of isolated nonpregnant human myometrium. Materials and Methods: The ability of tadalafil (25, 40, and 63 µM) to inhibit 55 mM KCl-induced contractility of isolated nonpregnant human myometrium was studied. The ability of the ATP-sensitive potassium channel blocker glibenclamide (10 µM) and the calcium-sensitive potassium channel (BKCa) blocker iberiotoxin (100 nM) to reverse the inhibitory effect of 40 µM tadalafil on 55 mM KCl-induced myometrial contractility was also studied. Results: Tadalafil produced a concentration-dependent inhibition of myometrial contractility that was statistically significant at 40 and 63 µM concentrations of tadalafil. The inhibition by tadalafil of myometrial contractility was statistically significantly reversed by the concurrent administration of glibenclamide and iberiotoxin. Conclusions: These results suggest that tadalafil inhibits human myometrial contractility by opening ATP-sensitive potassium channels and BKCa channels. The opening of these channels could have been due to the action of raised intracellular levels of cGMP due to inhibition of PDE-5 by tadalafil. The results suggest that tadalafil could be investigated for use in clinical conditions requiring relaxation of the myometrium. [ABSTRACT FROM AUTHOR]

Objective To determine the use of the active management of the third stage of labour in 15 university-based obstetric centres in ten developing and developed countries and to determine whether evidence-based practices were being used. Methods From March 1999 to December 1999, the Global Network for Perinatal and Reproductive Health (GNPRH) conducted an observational, cross-sectional survey to assess the use of the practice and its components. Prospective data on patient characteristics and the interventions used in the management of the third stage of labour were collected using standardized methods. Data on approximately 30 consecutive vaginal deliveries in each centre (452 in total) were included. Findings Significant intracountry and intercountry variation in the practice of the active management of the third stage of labour was found (111/452 deliveries used active management), which confirmed the existence of a large gap between knowledge and practice. Conclusion Areas identified for improvement are the urgent implementation of the evidence-based clinical management practice defined as the active management of the third stage of labour; increased accessibility to systematic reviews in developing countries; and the conduction of clinical trials that assess the impact of this intervention in other settings. [ABSTRACT FROM AUTHOR]

A 28-year-old multiparous lady presented to the Gynaecology outpatient department with a 12 × 5 cm warty growth in the vulva. A biopsy of the growth revealed condyloma acuminata of the vulva. Simple vulvectomy was done. A PCR of the specimen detected the presence of human papilloma virus (HPV)-16 which is usually considered as a high-risk HPV type for carcinogenesis. [ABSTRACT FROM AUTHOR]