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Abstract: Objective: This study aims to determine the incidence, timing, and risk factors of clinical venous thromboembolism. Methods: A cohort of patients who had major gynecologic cancer surgery between 1998 and 2008 was identified. Secondarily, a nested case–control design wherein patients who had clinical VTE within 90days after surgery were considered cases. Controls were matched on age, race, surgery date, and cancer site. Risk factors were evaluated for VTE within 90days, and late VTE between 8 and 90days. Results: We identified 4158 women, 18years or older, without a history of recent thrombosis. We observed 126 cases of clinical VTE within 90days of surgery (incidence 4%) of which 96 (76%) occurred after post-operative day 7. In a multivariable model including age, ASA, BMI, race, and site of cancer, only ovarian cancer was a significant predictor for VTE within 90days (HR 2.8; 95% CI 1.6, 5.0). In the nested case–control study, we identified hospital stay≥5days (OR 2.8; 95% CI 1.5, 5.1) and prior VTE (OR 2.6; 95% CI 1.1, 6.1) as significant risk factors for VTE within 90days. Only hospital stay ≥5days (OR 2.5; 95% CI 1.3, 4.7) was significantly associated with late VTE between 8 and 90days. Conclusion: In gynecologic cancer patients, over 75% of VTE are detected more than 7days after surgery. Patients with ovarian cancer, prolonged hospitalization, or a history of VTE are at highest risk of developing clinical VTE. Such patients would be optimal candidates for clinical trials evaluating extended VTE prophylaxis. [Copyright &y& Elsevier]

Abstract: Objectives: A putative model of spontaneous cancer has been described in the laying hen that bears significant similarities to human ovarian cancer. Our objective was to characterize and compare the patterns of gene expression in chicken and human forms of this disease. Methods: RNA from 20 localized and metastatic ovarian and oviductal chicken tumor samples was isolated, amplified using in vitro transcription, and hybridized against normal ovarian epithelium to a customized cDNA microarray constructed for these studies. Differentially expressed genes were identified for localized ovarian, metastatic ovarian, and oviductal (or tubal) cancer by class comparison using BRB-ArrayTools. Results were validated with semi-quantitative PCR. A gene list (prediction model) constructed with the class prediction tool was used in a human ovarian cancer microarray obtained from the GEO datasets (GSE6008) in order to compare these results across species. Results: Class comparison analysis between localized ovarian, metastatic ovarian and oviductal cancer yielded 41 different informative probes that coded for 27 unique genes. Localized ovarian samples clustered between metastatic ovarian and oviductal cancer samples. Using our chicken data as a training set and leaving oviductal samples out of the analysis, we created a prediction model that classified early stage and advanced stage human ovarian cancer gene expression arrays with 78% overall accuracy. Conclusions: Gene expression of spontaneous ovarian cancer in the chicken is comparable to gene expression patterns of human ovarian cancer. [ABSTRACT FROM AUTHOR]

Abstract: Objective. : HPV infection is a necessary but insufficient cause of cervical cancer. The significance of HPV DNA in blood however is debatable because of variable detection rates due to the differences in the methodology used. The aim of this study was to detect and quantitate HPV 16 and 18 plasma viremia in women with cervical neoplasia. Methods. : HPV DNA was detected in cervical tissue using consensus PGMY primers and genotyped using reverse line blot hybridization. HPV 16 and 18 quantitation in tissue and detection and quantitation in plasma was performed using sensitive real time PCRs targeting E6/E7 region of HPV 16/18 genome respectively. Results were correlated with viral loads in corresponding tissue and with clinical disease stage. Results. : Viremia was detected in 56.4% of HPV 16 positive women and 20% of HPV 18 positive women. The prevalence of HPV 16 DNA in plasma increased with advancing disease stage (p =0.001), although HPV 16 absolute plasma viral load was not significantly associated with advancing disease stage (p =0.281). There was no correlation between absolute plasma viral load and viral load in corresponding cervical tissue (Spearman''s rho=0.184, p =0.187). The prevalence of HPV 18 viremia and absolute HPV 18 plasma viral load were not associated with advancing disease stage (p =0.620, p =0.508). Conclusion. : The presence of HPV 16 in plasma is a marker of advancing cervical disease. [Copyright &y& Elsevier]

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]

Abstract: Objective: We have previously shown that TCEAL7 (transcription elongation factor A (SII)-like 7) is epigenetically down-regulated in the majority of epithelial ovarian cancers. We now examine the hypothesis that inherited alterations in TCEAL7 play a role in the etiology of ovarian cancer. Methods: A two-site case-control study of 930 cases of ovarian cancer and 1037 controls, frequency-matched on residence, age and race, was conducted. Six informative SNPs (tagSNPs and putative-functional SNPs) were genotyped. Logistic regression was used to adjust for potential confounders and determine if inherited variation at this locus was associated with risk of ovarian cancer in general and among cases with invasive disease and serous histology. Gene-level principal component and haplotype analyses were also conducted. Results: None of the SNPs or haplotypes studied were significantly associated with ovarian cancer risk overall. However, among the 440 invasive serous cases, the minor alleles for three correlated SNPs were significantly associated with reduced risk (p-values<0.05), summarized gene-level variation was weakly associated with reduced risk (p-value=0.05), and the predominant haplotype was less common among cases than controls (0.36 v 0.40, p-value=0.05), consistent with single-SNP results. Conclusion: TCEAL7 polymorphisms may play a role in the development of invasive serous ovarian cancers. Follow-up molecular and replication studies are warranted. [Copyright &y& Elsevier]

To determine the prevalence of physical violence during pregnancy and the factors associated with it.A population-based, multicentre, cross sectional household survey.Rural, slum and urban non-slum areas of Bhopal, Chennai, Delhi, Lucknow, Nagpur, Trivandrum and Vellore, in India.A total of 9938 women who were 15 to 49 years of age and living with a child younger than 18 years old.Probability proportionate to size sampling of households was performed in three strata. Trained field workers administered a structured questionnaire. Women who reported domestic violence were asked about violence during pregnancy. Outcome variables included six violent behaviours: slap, hit, kick, beat, use of weapon and harm in any other way. Moderate to severe violence was defined as experience of any one or more of the following behaviours: hit, beat or kick. Odds ratios were calculated for risk and protective factors of violence during pregnancy using logistic regression.Physical spousal violence.The lifetime experience, during pregnancy, of being slapped was 16%, hit 10%, beat 10%, kicked 9%, use of weapon 5% and harmed in any other way 6%. Eighteen percent of women experienced at least one of these behaviours and 3% experienced all six. The overall prevalence of moderate to severe violence during pregnancy was 13%. Logistic regression showed that the factors determining whether a woman experienced moderate to severe violence during pregnancy were: husband accusing wife of an affair (OR 7.1; 95% CI 5.1 to 9.8), dowry harassment (OR 4.1; 95% CI 2.8 to 6.1), husband having an affair (OR 3.7; 95% CI 2.8 to 4.8), husband being regularly drunk (OR 3.2; 95% CI 2.6 to 4.1), low education of husband (OR 2.8; 95% CI 1.4 to 5.6), substance abuse by husband (OR 2.6; 95% CI 1.3 to 5.5), no social support (OR 1.8; 95% CI 1.1 to 3.0), three or more children (OR 1.6; 95% CI 1.2 to 2.1) and household crowding (OR 1.1; 95% CI 1.0 to 1.2).In this study, 12.9% of women experienced moderate to severe physical violence during pregnancy. Suspicion of infidelity, dowry harassment, husband being regularly drunk and low education of husband were the main risk factors for violence during pregnancy. [ABSTRACT FROM AUTHOR]

Background: Molecular subtyping of endometrial carcinomas (EC) has been shown to classify tumors into prognostically relevant groups. Characterizing EC with a limited number of markers viz., POLE mutations, p53 mutations, and MMR status, can provide valuable information. Design: Paraffin sections of a cohort of 48 EC from a tertiary care center were characterized for the above-mentioned molecular markers and analyzed in the context of survival. Methods: Formalin fixed paraffin embedded tissues from 48 EC were characterized for POLE mutations by Sanger sequencing (exons 9–14), for MMR (MLH1, MH2, MSH6) using immunohistochemistry (IHC) and copy number (high/low) using p53 IHC. Mutational status was integrated along with the clinicopathological details and survival analysis performed. Results: Eleven (22.9%) patients were MMR deficient, 3 (6.3%) had POLE mutation, while 2 (4.1%) had both POLE and P53 mutations (regarded as multiple classifiers). Twelve (25%) patients were found to have P53 mutations, while the remaining 20 (41.7%) had no specific molecular profile (NSMP). Median follow-up duration was 43.5 (2–62) months with 8 recurrences and 9 deaths. Tumors with POLE mutation had the most favorable prognosis followed by the NSMP and the MMR mutated group while the P53 and multiple classifier groups had the worst prognosis in terms of OS (Log-rank p: 0.006) and PFS (Log-rank p: 0.001). Conclusion: The integration of molecular-clinicopathologic data for endometrial cancer classification, through cost-effective, clinically applicable assays appears to be a highly objective tool that can be adopted even in resource-limited settings. It has the potential to cause a shift in the paradigm of EC pathology and management practice. [ABSTRACT FROM AUTHOR]

To meet global cervical cancer elimination efforts, a wider range of affordable and accessible vaccines against human papillomavirus (HPV) are needed. We aimed to evaluate the immunogenicity and safety of a quadrivalent HPV vaccine (targeting HPV types 6, 11, 16, and 18), developed and manufactured by the Serum Institute of India (SIIPL). Here we report outcomes in the 9–14 years cohort. This randomised, active-controlled, phase 2/3 trial was conducted at 12 tertiary care hospitals across India. Healthy participants aged 9–14 years or 15–26 years with no history of HPV vaccination were eligible for enrolment. Female participants were randomly assigned (1:1) with an interactive web response system, by use of a central computer-generated schedule and block randomisation (block sizes of 2, 4, 6, and 8), to receive the SIIPL quadrivalent HPV vaccine (Cervavac; SIIPL, Pune, India) or the comparator quadrivalent HPV vaccine (Gardasil; Merck Sharp & Dohme, Harleem, the Netherlands). Participants, investigators, laboratory technicians, and sponsors were masked to treatment allocation of female participants. Male participants were given the SIIPL quadrivalent HPV vaccine in an open-label manner. Study vaccines were administered intramuscularly with a two-dose schedule (at day 0 and 6 months) in the cohort aged 9–14 years, and with a three-dose schedule (at day 0, month 2, and month 6) in the cohort aged 15–26-years. Immunogenicity was assessed 30 days after the last dose by use of multiplexed ELISA. The primary outcome was the non-inferiority of immune response in terms of the geometric mean titre (GMT) of antibodies against HPV types 6, 11, 16, and 18 generated by the SIIPL quadrivalent HPV vaccine in girls and boys (aged 9–14 years) compared with the GMT generated by the comparator quadrivalent HPV vaccine in women aged 15–26 years at month 7 in the modified per-protocol population (ie, all participants who received all doses of study vaccines per assigned treatment group and had both day 0 and 1-month immunogenicity measurements after the last dose following protocol-defined window periods with no major protocol deviations). Non-inferiority was established if the lower bound of the 98·75% CI of the GMT ratio was 0·67 or higher. The co-primary outcome of occurrence of solicited adverse events (within 7 days of each dose) and unsolicited adverse events (up to 30 days after the last dose) was assessed in all participants who were enrolled and received at least one dose of study vaccine. The trial is registered with the Clinical Trials Registry – India (CTRI/2018/06/014601), and long-term follow-up is ongoing. Between Sept 20, 2018, and Feb 9, 2021, 2341 individuals were screened, of whom 2307 eligible individuals were enrolled and vaccinated: 1107 (738 girls and 369 boys) in the cohort aged 9–14 years and 1200 (819 women and 381 men) in the cohort aged 15–26 years. No race or ethnicity data were collected. 350 girls and 349 boys in the SIIPL quadrivalent HPV vaccine group and 338 women in the comparator vaccine group were included in the modified per-protocol population for the primary endpoint analysis. The median follow-up for the analyses was 221 days (IQR 215–231) for girls and 222 days (217–230) for boys in the SIIPL quadrivalent HPV vaccine group, 223 days (216–232) for girls in the comparator vaccine group, and 222 days (216–230) for women in the comparator vaccine group. GMT ratios were non-inferior in girls and boys receiving the SIIPL quadrivalent HPV vaccine compared with women receiving the comparator vaccine: GMT ratios for girls were 1·97 (98·75% CI 1·67–2·32) for HPV type 6, 1·63 (1·38–1·91) for HPV type 11, 1·90 (1·60–2·25) for HPV type 16, and 2·16 (1·79–2·61) for HPV type 18. For boys the GMT ratios were 1·86 (1·57–2·21) for HPV type 6, 1·46 (1·23–1·73) for HPV type 11, 1·62 (1·36–1·94) for HPV type 16, and 1·80 (1·48–2·18) for HPV type 18. The safety population comprised all 1107 participants (369 girls and 369 boys in the SIIPL quadrivalent HPV vaccine group, and 369 girls in the comparator group). Solicited adverse events occurred in 176 (48%) of 369 girls and 124 (34%) of 369 boys in the SIIPL vaccine group and 179 (49%) of 369 girls in the comparator vaccine group. No grade 3–4 solicited adverse events occurred within 7 days of each dose. Unsolicited adverse events occurred in 143 (39%) girls and 147 (40%) boys in the SIIPL vaccine group, and 143 (39%) girls in the comparator vaccine group. The most common grade 3 unsolicited adverse event was dengue fever, in one (<1%) girl in the SIIPL vaccine group and three (1%) girls in the comparator group. There were no grade 4 or 5 adverse events. Serious adverse events occurred in three (1%) girls and three (1%) boys in the SIIPL vaccine group, and five (1%) girls in the comparator vaccine group. No vaccine-related serious adverse events were reported. There were no treatment-related deaths. We observed a non-inferior immune response with the SIIPL quadrivalent HPV vaccine in girls and boys aged 9–14 years and an acceptable safety profile compared with the comparator vaccine. These findings support extrapolation of efficacy from the comparator vaccine to the SIIPL quadrivalent HPV vaccine in the younger population. The availability of the SIIPL quadrivalent HPV vaccine could help meet the global demand for HPV vaccines, and boost coverage for both girls and boys globally. Biotechnology Industry Research Assistance Council, Department of Biotechnology (DBT), Government of India, and Serum Institute of India. [ABSTRACT FROM AUTHOR]

Objective: To determine the accuracy of high‐risk human papillomavirus (HPV) DNA samples on filter paper in comparison to specimen transport medium (STM). Methods: This was a cross‐sectional diagnostic study of 42 consecutive women who were prospectively recruited. Each had self‐collected vaginal samples on filter paper, physician‐collected cervical samples on filter paper, and physician‐collected cervical samples in STM. HPV DNA testing was performed with a Hybrid Capture 2 system (Qiagen). Sensitivity, specificity, negative predictive value (NPV), positive predictive value (PPV), and agreement of filter paper methods with the standard procedure were calculated. Results: The overall prevalence of HPV in STM was 67.5%. Detection of HPV DNA in the physician‐collected cervical samples on filter paper had a sensitivity of 77.8%, a specificity of 100%, a PPV of 100%, and an NPV of 68.4%. The patient's self‐sampling on filter paper had a sensitivity of 66.7%, a specificity of 100%, a PPV of 100%, and an NPV of 59.1%. The agreement between STM method and physician‐collected sample on filter paper was substantial, (κ = 0.695, P < 0.001), while the agreement between STM and self‐collected samples on filter paper was moderate (κ = 0.565, P < 0.001). Most patients reported that self‐collection was acceptable (100%), painless (95%), and not embarrassing (95%). Conclusion: Filter paper, with dried self‐collected vaginal samples, can be used to detect high‐risk HPV with acceptable accuracy. Synopsis: Self‐collected vaginal samples on filter paper, to detect high‐risk human papillomavirus, is better for women, easier to transport to central laboratories, and has acceptable accuracy. [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]

Enhanced recovery protocols consist of a bundle of concepts including early feeding, opioid-sparing multimodal pain management, and euvolemia, with the overarching goal of hastening postoperative recovery. Enhanced recovery after surgery has been shown to reduce hospital length of stay, reduce costs, and decrease perioperative opioid requirements in benign and oncologic gynecologic surgery. Interventions without supporting evidence of benefit, such as the use of mechanical bowel preparation, routine use of nasogastric tubes and surgical drains, caloric restriction, routine use of intravenous opioid analgesics, and over-vigorous intravenous hydration should be discouraged to improve broader endpoints such as patient satisfaction and overall recovery. Successful implementation requires engagement from a multidisciplinary team including surgeons, anesthesiologists, nurses, and pharmacists. [ABSTRACT FROM AUTHOR]

Objective: To determine the prevalence and study the association of ovarian, uterine, and breast cancers with endometriosis. Methods: A cross‐sectional study of all women with a tissue‐proven diagnosis of endometriosis postoperatively in a tertiary care hospital between January 1, 2010, and December 31, 2019, was conducted to determine the prevalence of coexistent malignancy. Patient details were obtained from electronic clinical records. Univariate analysis followed by multivariate analysis was done to find independent risk factors associated with malignancy. Results: Out of 800 patients, 104 (13.0%) were found to have coexistent malignancy: ovarian (50, 6.2%); endometrial (33, 4.1%); synchronous ovarian and endometrial (7, 0.9%); and breast (14, 1.8%). Increasing age (odds ratio [OR] 1.13; 95% confidence interval [CI] 1.09–1.16), higher levels of cancer antigen 125 (CA 125) (OR 1.002; 95% CI 1.001–1.005), postmenopausal status (OR 6.2; 95% CI 2.0–19.2), duration of endometriosis over 5 years (OR 4.7; 95% CI 2.5–9.0), and endometriomas larger than 8 cm (area under the curve 0.83) were predictive of coexistent malignancy. Conclusion: Endometriosis is associated with an increased risk of ovarian, endometrial, and breast malignancy. Increasing age, postmenopausal status, higher levels of CA 125, larger endometrioma, and long‐standing disease are predictive risk factors. Synopsis: Endometriosis is associated with increased risk of breast and gynecologic malignancies. Increasing age, postmenopausal status, larger endometriomas, and long‐standing endometriosis are the predictive risk factors. [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]

Abstract: Objective: To determine the effect of a nicorandil congener, SG-209 on the myometrium. Study design: Isolated strips of myometrium, from nine women who underwent hysterectomy, were made to contract with 55mM KCl before and after incubation with three concentrations of SG-209 (1.5, 3.0 and 10μM). The mean height of contraction and the area under the curve were analysed using a non-parametric test. Results: At a 10μM concentration, SG-209 significantly decreased the mean area under the curve from 10.8 to 2.5cm2 (p <0.05). Conclusion: SG-209 significantly relaxes the human non-pregnant myometrium. Along with its congener, nicorandil, it may be useful in clinical conditions that require uterine relaxation. [Copyright &y& Elsevier]

Abstract: In a cross-sectional study performed between June 2001 and November 2003, the HPV 16 E6 gene of 50 women with cervical neoplasia and 20 cytologically normal women (‘controls’) was sequenced following amplification by PCR. The 350T to G variant was seen in 35 (70%) of 50 patients'' isolates while it was seen in only 3 (15%) of the 20 isolates from the ‘controls’. The higher occurrence of the 350G variant among the patients was statistically significant (P&#60;0.01). Isolates from patients were grouped into the European (E), Asian-American (AA) and North-American (NA-1) phylogenetic clusters with 46 (92%) belonging to the E cluster. All the 20 isolates from ‘controls’ belonged to the E cluster. This study suggests an association of the HPV 16 350G variant with a higher risk of cervical neoplasia and a predominance of E lineage strains among Indian HPV 16 isolates. [Copyright &y& Elsevier]

Background: HPV DNA has been detected in metastatic tumour and HPV plasma viraemia may indicate a poor prognosis and a high risk for metastasis. Objective: Detection of HPV DNA in plasma of patients with cervical carcinoma. Study design: A cross-sectional study was done, wherein cervical biopsies and plasma samples were collected from 58 women with invasive cervical carcinoma, 10 women with cervical intraepithelial neoplasia (CIN) and 30 control women in the same age range. Polymerase chain reaction (PCR) was employed to detect the presence of HPV DNA. Samples positive for HPV DNA were typed by restriction fragment length polymorphism (RFLP). To confirm that the HPV sequence in plasma was identical to that in tissue, sequencing was done on all the paired plasma and tissue samples. Results: All the 30 paired cervical tissue and plasma samples from the controls were negative for HPV DNA. HPV DNA was detectable in cervical tissues of 55 (94.8%) of 58 patients with invasive cervical carcinoma and in all 10 patients (100%) with CIN and in eight (11.8%) of the total 68 plasma samples from patients. All eight plasma samples were from women with invasive cervical carcinoma with three each in stages IIIB and IV and one each in stages IIB and IB, respectively. Of the eight positive samples, seven were typed as HPV-16 and 1 as HPV-58. HPV types detected in cervical tissue and plasma pairs from these eight patients correlated as revealed by RFLP and sequencing. A patient with stage IB cancer had detectable HPV DNA in the external iliac lymph node, removed at Wertheims hysterectomy, which was histopathologically free of tumour. The HPV type in the node, was the same as that present in the paired tissue and plasma sample. Conclusions: HPV DNA is detectable in the plasma of patients with advanced cervical cancer. [Copyright &y& Elsevier]

Specific nucleotide variations in the E2 DNA sequence were looked for in samples with an intact human papillomavirus (HPV) 16 episomal E2 DNA.Ninety-two women, 76 with invasive cervical carcinoma and 16 with cervical intraepithelial neoplasia (CIN) were recruited. HPV DNA typing was performed by polymerase chain reaction (PCR) based restriction fragment length polymorphism (RFLP). Intact episomal E2 DNA of HPV 16 was detected by PCR. Important nucleotide variations in samples with amplifiable E2 DNA were detected by RFLP. Nucleotide sequencing was performed on representative samples to confirm RFLP findings.A total of 89 (96.7%) women were positive for HPV DNA. Of these, 56 (63%) were positive for HPV 16, and of these, 38 (68%) were positive for intact episomal HPV 16 E2 DNA while 18 (32%) were negative. Samples with intact episomal HPV 16 E2 DNA sequences were grouped into four different digestion profiles I to IV based on RFLP patterns. Digestion patterns revealed absence of any sequence variations in samples with digestion profile I and presence of a 2983 A-G variation in those with profile II. Samples with digestion profiles III and IV revealed three variations in the hinge region (3516 C-A, 3538 A-C, 3566 T-G) and two in the DNA binding domain (3684 C-A, 3694 T-A) of the E2 sequence. Sequencing performed on representative samples confirmed RFLP findings.PCR-RFLP helped in the identification of important HPV 16 E2 sequence variations, circumventing the need for sequencing. The presence of the nucleotide variations in positions that could alter the biological and immunological functions of the E2 protein combined with its increased occurrence in this study bring out the importance of these variations. [Copyright &y& Elsevier]

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]

Aim: To assess the relevance of enlarged cardiophrenic lymph nodes (CPLN) seen on staging CT of ovarian cancer patients. Methods: Retrospective cohort study of consecutive patients with primary ovarian malignancy who underwent staging CT between 2013 and 2016. Images were reviewed by two radiologists in consensus. Enlarged CPLN was defined as a short axis diameter ≥ 7 mm. Clinical and imaging findings; management decisions; outcome of cytoreductive surgery and survival were compared between patients with and without enlarged CPLN on staging CT. Results: Enlarged CPLN were found in 42 patients (41.5%) and was significantly associated with higher radiological PCI (p = 0.002); large volume upper abdominal disease (p = 0.001); enlarged lesser omental, periportal and supra-renal para-aortic lymph nodes (p ≤ 0.05); unfavorable sites of disease involvement (p < 0.001) and extraperitoneal metastases (p = 0.004). While there was a significant difference in the number of patients who underwent primary and interval debulking (p = 0.002), there was no difference in the rates of optimal cytoreduction between the two groups (p = 0.469). After adjusting for outcomes of cytoreductive surgery, CT detected enlarged CPLN did not adversely affect the overall survival, HR 1.5 (0.708–3.4), p = 0.272, but adversely affected the recurrence free survival (HR 2.38 (1.25–4.53)), p = 0.008. Conclusions: Enlarged CPLN detected on staging CT in patients with primary ovarian cancer is clinically significant even in the developing world and is associated with higher volume of peritoneal, non-regional nodal and extraperitoneal disease and lower recurrence free survival. [ABSTRACT FROM AUTHOR]

Human papillomavirus (HPV) vaccination offers an excellent prospect for the primary prevention of cervical cancer. The bivalent and quadrivalent vaccines are both available in India. The nonavalent vaccine is licensed but not yet available. However, there still remain controversies regarding the vaccination of older women, immunocompromised females and other special groups. To provide recommendations for HPV vaccination in India. The Federation of Obstetric and Gynecological Societies of India (FOGSI) convened an expert group on cervical cancer prevention to formulate good clinical practice recommendations (GCPR) with respect to vaccine efficacy and safety, target groups, optimal timing and dosing schedules. HPV vaccines are licensed for females aged 9–45 years in India and have been seen to be safe and effective. FOGSI recommends HPV vaccination of all girls <15 years of age as the best target group, in whom two‐doses at an interval of 6 months, extendable to 18 months, are recommended. Three‐doses are recommended in girls >15 years of age, immunocompromised persons and sexual assault survivors. Older women and women with abnormal screening results may be vaccinated with an understanding that vaccination does not protect against already acquired infections and screening has to continue. Single‐dose vaccination results are promising. Increased awareness is required to reduce vaccine hesitancy. HPV vaccination should be the priority to achieve the elimination of cervical cancer. The introduction of affordable HPV vaccines and reduced dose schedules will improve coverage. [ABSTRACT FROM AUTHOR]

Background: The Indian HIPEC registry is a self-funded registry instituted by a group of Indian surgeons for patients with peritoneal metastases (PM) undergoing surgical treatment. This work was performed to  • Evaluate outcomes of cytoreductive surgery ± HIPEC in patients enrolled in the registry.  • Identify operational problems. Methods: A retrospective analysis of patients enrolled in the registry from March 2016 to September 2017 was performed. An online survey was performed to study the surgeons' attitudes and existing practices pertaining to the registry and identify operational problems. Results: During the study period, 332 patients were enrolled in 8 participating centres. The common indication was ovarian cancer for three centres and pseudomyxoma peritonei for three others. The median PCI ranged from 3 to 23. A CC-0/1 resection was obtained in 94.7%. There was no significant difference in the morbidity (p = .25) and mortality (p = .19) rates between different centres. There was a high rate of failure-to-rescue (19.3%) patients with complications and the survival in patients with colorectal PM was inferior. A lack of dedicated personnel for data collection and entry was the main reason for only 10/43 surgeons contributing data. The other problem was the lack of complete electronic medical record systems at all centres. Conclusions: These results validate existing practices and identify country-specific problems that need to be addressed. Despite operational problems, the registry is an invaluable tool for audit and research. It shows the feasibility of fruitful collaboration between surgeons in the absence of any regulatory body or funding for the project. [ABSTRACT FROM AUTHOR]

Background and Objectives. Angioleiomyoma is a benign perivascular neoplasm commonly involving subcutaneous tissue of extremities, head, and trunk region. They rarely involve the female genital tract. This study analyses clinicopathological features of 6 cases of uterine angioleiomyoma. Methods. Routine sections of 6 cases were reviewed and immunohistochemical markers namely muscle-specific actin, h-caldesmon, desmin, CD10, WT-1, HMB-45, and melan-A were done. Results. Of the 6 cases, 4 cases had tumor involving the corpus and 2 cases had tumor in the cervix. Grossly, all tumors had a whorled and congested cut surface. Microscopic examination of all the cases revealed circumscribed neoplasms composed of interlacing fascicles of benign perivascular smooth muscle cells with evenly distributed slit-like blood vessels (solid variant) along with vessels exhibiting thick muscular walls with swirling pattern (venous variant). In only 2 cases many dilated vessels were seen (cavernous variant). Immunohistochemically, all cases were positive for muscle-specific actin, h-caldesmon, and desmin. All cases were negative for CD10 and WT-1 ruling out endometrial stromal tumor and were negative for HMB-45 and melan-A ruling out perivascular epithelioid cell tumor (both endometrial stromal tumor and perivascular epithelioid cell tumor have prominent vessels but have different histomorphology). In all cases, surgical excision was curative and there were no intraoperative or postoperative complications. Follow-up of all the cases has been unremarkable. Conclusion. As the World Health Organization has not included angioleiomyoma in the classification of mesenchymal tumors of uterine corpus and cervix, we recommend that it should be included in the classification. [ABSTRACT FROM AUTHOR]

Objectives: There were two objectives: (1) to assess the survival outcome of endometrial cancer based on surgical and adjuvant treatment and (2) to note patterns of and risk factors for recurrence in endometrial cancer. Design: This was a retrospective analysis of the hospital records of women diagnosed with carcinoma of the endometrium who were operated on in the Division of Gynecologic Oncology, Christian Medical College, Vellore, India, from January 2011 to December 2013. Materials and Methods: Electronic patient records of 152 women with endometrioid endometrial cancer were obtained and used to analyze their surgical outcomes. Information regarding survival and recurrences was obtained by various methods. Survival was assessed by Kaplan-Meir survival analysis. Results: The tumors were endometrioid adenocarcinomas in 94.7% of the patients. The majority of the patients were stage IA (49.3%) and stage IB (22.3%). A few patients also had occult stage II (6.6%), and 21% had advanced stage cancer. Seventy-seven (50.7%) women needed adjuvant treatment after risk stratification, with 53.6% receiving radiation only as brachytherapy (35.6%), external pelvic radiation (13.5%), or a combination of both (50.9%); 15.9% received chemotherapy; and 30.4% had radiation and chemotherapy. The 3-year survival of endometrial cancers was 94.5% and disease-free survival was 91.4%. The rate for recurrence was 8.6% and for mortality 5.5%. Recurrences were equal in distribution for local and distant metastasis. Complications of surgical treatment were minimal. Conclusions: Endometrial cancers tend to present as early stage cancers in the majority of cases. Appropriate risk stratification and liberal use of chemotherapy when indicated may improve survival in high-risk cases. (J GYNECOL SURG 2017:1) [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]

Background: Extrauterine fibroids are rare and are usually difficult to diagnose. Benign metastasizing leiomyomatosis (BML) is characterized by multiple smooth-muscle nodules located on the peritoneum, omentum, or rest of peritoneal surface. Case: A 42-year-old woman presented for a routine gynecologic examination; an ultrasound revealed that she had a fibroid in her uterus and an endometriotic cyst. Intraoperatively, it was noted that she had a chocolate cyst of the left ovary and multiple fibroids on her uterus, broad ligament, sigmoid colon, omentum, and liver surface. She underwent excision of all these fibroids. She was also advised to undergo computed tomography (CT) to check for lesions in her lungs. A few lesions were noted. She was treated with letrozole postoperatively. Results: Follow-up at 15 months showed no evidence of recurrence. She had a repeat CT scan of her thorax, which showed no increase in the size of the lesions in her lungs. Conclusions: Aromatase inhibitors can be used successfully to treat benign metastasizing leiomyomatosis. Further reports are also needed to find the role of aromatase inhibitors in BML. (J GYNECOL SURG 32:193) [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]