Analysis of patients with endometrial carcinoma using the ProMise classifier: a pilot study from India.

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.

Immunogenicity and safety of a new quadrivalent HPV vaccine in girls and boys aged 9-14 years versus an established quadrivalent HPV vaccine in women aged 15-26 years in India: a randomised, active-controlled, multicentre, phase 2/3 trial.

BACKGROUND: 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. METHODS: 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. FINDINGS: 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. INTERPRETATION: 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. FUNDING: Biotechnology Industry Research Assistance Council, Department of Biotechnology (DBT), Government of India, and Serum Institute of India.

A longitudinal study of sexual health and quality of life in endometrial carcinoma survivors.

OBJECTIVES: This study aimed to assess sexual health and quality of life (QoL) in endometrial cancer survivors and the factors influencing these variables. METHODS: A mixed method design comprising quantitative (cohort design) and qualitative (face-to-face interviews) aspects was chosen. A total of 132 patients who underwent surgery alone, surgery followed by adjuvant vaginal brachytherapy, or surgery followed by chemotherapy and radiation were included. Female Sexual Function Index (FSFI) and Functional Assessment of Cancer Therapy General (FACT-G) questionnaires were used to assess the participants' sexual health and QoL at 6 months and 1 year post-treatment. Multivariate logistic regression models were used to analyze the factors associated with general and sexual well-being. RESULTS: At 1 year, 89% of the participants still had low sexual function scores. Survivors over 50 years (OR 284.7, 95% CI 13 to 364, p<0.001) and educated below graduate level (OR 26.8, 95% CI 2 to 370, p=0.014) had low sexual function scores. Patients who had surgery alone had better QoL than those who received adjuvant radiation. Women who had surgery, chemotherapy, and radiation had the lowest QoL scores (OR 6.4, 95% CI 2.1 to 19.5, p=0.001). All scores improved with time. CONCLUSIONS: This study demonstrated the high prevalence of low sexual function and poor QoL in endometrial cancer survivors. There was a communication gap between the women and their partners as well as their healthcare providers. This study highlights the need for discussion about the survivors' sexual well-being and QoL.

Training for next-generation gynaecologic surgical & radiation oncologists - opportunities & challenges.

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.

Human papillomavirus vaccination: Good clinical practice recommendations from the Federation of Obstetric and Gynecological Societies of India.

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.

Treading the beaten path with old and new obstacles: a report from the Indian HIPEC registry.

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.

The BRCA mutation spectrum among breast and ovarian cancers in India: highlighting the need to screen BRCA1 185delAG among South Indians.

Mutations in BRCA1 and BRCA2 significantly elevate the risk of developing breast and ovarian cancer. Limited data exists regarding the prevalence of BRCA mutations, and optimal, cost-effective testing strategies in developing countries like India. This study aimed to evaluate the utility of a Next Generation Sequencing (NGS) panel for BRCA1/2 mutation testing among women diagnosed with, or at risk of developing hereditary breast and ovarian cancers. We also aimed to identify population specific BRCA1/2 mutation hotspots, to enable the development of more affordable testing strategies. We identified 921 patients with breast and ovarian cancer who underwent mutation testing. The target enrichment was followed by targeted NGS in 772 patients and an allele-specific PCR (ASPCR) based genotyping for BRCA1:c.68_69delAG (or 185delAG), was carried out in 149 patients. We identified 188 (20.4%) patients with BRCA1/2 variants: 118 (62.8%) with pathogenic/likely pathogenic and 70 (37.2%) with VUS. The 185delAG was identified as a recurrent mutation in the Southern Indian population, accounting for 24.6% of the pathogenic variants. In addition, a family history of breast, ovary, pancreas, or prostate (BOPP) cancer was found to be associated with an increased risk of identifying a deleterious BRCA1/2 variant [OR = 2.11 (95% CI 1.45-3.07) p ≤ 0.001]. These results suggest that Targeted NGS is a sensitive and specific strategy for BRCA testing. For Southern Indian patients, a two-tiered approach can be considered: Initial screening with ASPCR for BRCA1 185delAG followed by NGS for those testing negative. Expanding the gene panel and identifying other population-specific mutation hot spots is a promising area with potential for improvements in testing and treatment strategies.

Diagnostic study of human papillomavirus DNA detection in cervical and vaginal samples using the filter paper card.

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.

The clinico pathological features and survival in serous endometrial cancers.

Background & Introduction: Serous cancers are a biologically aggressive variety of endometrial cancer (EC) with a high rate of recurrence and mortality among all the subtypes. Herein we describe our experience with serous endometrial cancer. Objective: This study was conducted to identify the clinicopathological characteristics, treatment modalities and survival outcomes in women diagnosed with serous endometrial malignancies. Methods: This was a retrospective descriptive analysis of data on patients diagnosed with serous endometrial tumours between January 2010 to September 2019 in our institute collected from electronic medical records. Descriptive statistics such as proportions, means and standard deviations and Cox regression hazards model on risk factors were performed. Survival was plotted by Kaplan-Meier curves. Results: During the study period, 32 (5.7%) patients out of 564 diagnosed cases of endometrial cancer had serous histology. The mean age at diagnosis was 62.5 years (SD 7.6) while mean BMI was 26.4 kg/m2 (SD 4.6). Staging laparotomy was done in 27(84%) of the patients. Advanced stages (III and IV) were detected in 16 patients (50%) at primary surgery.Adjuvant chemo therapy and radiation was received by 21(65.6%) patients therapy. Out of 32 patients, 13 (40%) developed recurrence while another 13 expired. Stage at diagnosis and type of adjuvant therapy were important factors in determining the outcome. Median recurrence free and overall survival was 22(95% CI 1.4-42) and 36 months (95% CI 10.1-61.8) respectively. Conclusion: Serous endometrial cancers are an intrusive subtype of EC. Comprehensive surgical staging with optimal cytoreduction should be aimed at. Adequate upfront molecular categorization of these tumors is mandated. Adjuvant therapy with chemotherapy and radiation is given in postoperative setting. Targeted therapies and immunotherapy could be considered in recurrences.

Role of squamous cell carcinoma antigen in prognostication, monitoring of treatment response, and surveillance of locally advanced cervical carcinoma.

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.

Survival outcomes of epithelial ovarian cancer treated at a tertiary-level hospital in India.

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 2015table 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.

ERAS: An Audit of Existing Practices.

Objectives: Enhanced recovery after surgery (ERAS) is a set of multidisciplinary, evidence proven guidelines which enhance perioperative recovery in various surgical branches. This study was planned as a pilot effort with the aim of evaluating the surgical team's compliance to ERAS, in the absence of a structured programme, in the department of gynaecologic oncology of a tertiary care hospital in India. Methods: This is a retrospective audit of patients who underwent elective surgery, in the department of gynaecologic oncology, in a tertiary care centre in India, between 15th August 2019 to 15th October 2019. Emergency operations and those surgeries with palliative intent were excluded from the study. Electronic outpatient and inpatient records of patients chosen by convenient sampling were examined. Adherence to 18 components (pre-operative, intra-operative and post-operative) from the ERAS guidelines pertaining to surgical care were analysed. Results: A total of 50 patients were included. Mean age group was 50 years (22-76 years). Majority of patients (60%) had a Charlson Deyo score of 0. Excellent compliance was noted with respect to preoperative counselling (94%), intraoperative management (86%) and post-operative factors such as early ambulation, thromboprophylaxis and early discharge. Practices which required improvement included reduction of period of pre-operative fasting, prehabilitation, carbohydrate loading, gum chewing and coffee consumption and early initiation of feeding in post-operative period. Conclusion: Dedicated and co-ordinated team effort will ensure that an ERAS protocol is enforced. Periodic auditing will reveal inconsistencies in compliance and guarantee benefit to patients.

Vulval Intraepithelial Neoplasia 3: A Clinico-Pathological Review in a Tertiary Care Centre Over 10 Years.

Objectives: Vulval Intraepithelial Neoplasia 3 (VIN) is a chronic, premalignant condition affecting the vulval skin. The age standardised incidence is approximately one per 100,000 women, with a peak at 30-49 years of age, and has risen over recent decades. This study would analyse the pattern of presentation, diagnosis, treatment and follow up of patients diagnosed with VIN 3 over a period of ten years at a tertiary care centre in India. Materials and Methods: This was a retrospective study conducted on all patients diagnosed to have VIN 3 between 1 January 2010 to 30 November 2019 in the Department of Gynaecologic Oncology, Christian Medical College, Vellore were included in this study. The outpatient records of the patients were obtained from an electronic registry. Results: A total of 18 patients were diagnosed of VIN 3 during this time period. Sixteen patients were older than 50 years. Abnormal PAP was noted in 10 patients (HSIL-7, LSIL-2, ASC-H-1). Four patients had coexisting VAIN 3. About 16 patients underwent primary simple vulvectomy or wide local excision. Two patients were managed conservatively. Nine patients had recurrence with mean disease free interval of 12.5 months (4-36 months). Cryotherapy was used in 2 patients. Imiquimod was used in 3 patients. Surgical margins was achieved in 7 patients out of which 5 patients had recurrence. About 50% of patients with involved margins on biopsy had recurrence. Mean duration of follow up was 17 months (4-105 months). About 8 patients developed squamous cell carcinoma of genital tract on follow up. Conclusion: VIN 3 has a high rate of progression to invasive SCC. Regression of VIN is rare. Proper follow up and treatment of VIN 3 goes a long way in preventing the morbidity associated with vulval cancer.

Incidence and timing of venous thromboembolism after surgery for gynecological cancer.

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 90 days after surgery were considered cases. Controls were matched on age, race, surgery date, and cancer site. Risk factors were evaluated for VTE within 90 days, and late VTE between 8 and 90 days. RESULTS: We identified 4158 women, 18 years or older, without a history of recent thrombosis. We observed 126 cases of clinical VTE within 90 days 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 90 days (HR 2.8; 95% CI 1.6, 5.0). In the nested case-control study, we identified hospital stay ≥ 5 days (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 90 days. Only hospital stay ≥ 5 days (OR 2.5; 95% CI 1.3, 4.7) was significantly associated with late VTE between 8 and 90 days. CONCLUSION: In gynecologic cancer patients, over 75% of VTE are detected more than 7 days 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.

Comparison of gene expression patterns between avian and human ovarian cancers.

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.

Endometriosis and malignancy: The intriguing relationship.

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.

P16INK4a/ki67 Immunocytochemistry in Improving the Predictive Value for High Grade Cervical Intraepithelial (≥CIN2) Neoplasia in Pap Smear.

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.

Diagnostic Accuracy of Fluorescein Sodium for Targeted Cervical Biopsies.

BACKGROUND: Visual inspection methods for cervical cancer screening are widely used in low resource settings. Fluorescent sodium could improve accuracy of cancer screening. This study aimed to assess diagnostic accuracy of fluorescein sodium (FNa) to detect cervical neoplasia. METHODS: Seventy consecutive patients referred for colposcopy were enrolled prospectively. Acetic acid, Lugol's iodine, and FNa were used sequentially. Biopsies were taken from all abnormal areas. If there was no obvious abnormality, two random biopsies and endocervical curettage were done. Reference standard was the highest grade lesion on cervical biopsy with a threshold of CIN2+. The patterns of each staining agent were recorded as absent, faint, or distinct. Diagnostic accuracy estimates with 95% confidence intervals were calculated. Correlation between the various tests were also determined using the kappa statistic. RESULTS: There were 27 cases of CIN2+ (38.6%). The sensitivity of any fluorescence for CIN2+ was 82% (62, 94) and for distinct fluorescence was 59% (39, 78). The specificity was 65% (49, 79) for any fluorescence and 95% (84, 99) for distinct fluorescence, the same as for Swede score > 7. For any fluorescence, the positive likelihood ratio was 2.34 (1.5, 3.65) and the negative likelihood ratio was 0.28 (0.13, 0.65). For distinct fluorescence, the positive likelihood ratio was 12.74 (3.18, 51.1) and the negative likelihood ratio was 0.43 (0.27, 0.68). There was moderate correlation between FNa and the other tests. CONCLUSION: Distinct fluorescence with FNa was very specific, low cost, and easy to perform and may contribute to confirm CIN2+ disease.

Treatment Outcomes of Early Carcinoma Cervix Before and After Sub-specialization.

This study aimed to compare the treatment outcomes in carcinoma cervix before and after gynecologic oncology sub-specialization at a tertiary care hospital, in India. This was a retrospective cohort study comparing women with operable cervical cancer who underwent radical hysterectomy before and after gynecologic oncology sub-specialization. Electronic medical records of women operated for early carcinoma cervix between 2001 and 2010 and 2011-2015 were reviewed and compared for treatment and oncological outcomes. Seventy-four patients were operated over 5 years after sub-specialization as against 59 over 10 years before sub-specialization, with similar clinical characteristics. After surgical-pathological examination, both cohorts were comparable with regard to mean tumor size, lymph nodes retrieved, deep stromal invasion, and involvement of lymph nodes, parametrium, and vaginal margins. After sub-specialization, the rate of intraoperative (3% versus 14%, p = 0.018) and postoperative complications (15% versus 46%, p < 0.001) was lower. Adjuvant radiation was used more after sub-specialization (50% versus 24%, p < 0.001). The follow-up rates were similar in both groups with comparable 5-year recurrence-free survival and overall survival rates. The hazard ratio for death after sub-specialization was 0.39 (95% CI 0.12 to 1.22) after adjusting for histology, stage, grade, and presence of intermediate or high risk factors. Gynecological oncologic sub-specialization decreased intraoperative and postoperative complications, improved pathological reporting, and enabled appropriate tailoring of adjuvant therapy.

Metastatic Tumors to the Ovary-a Surgeon's Dilemma.

The ovary is a common site of metastasis. Differential diagnosis of ovarian carcinomas, including secondary tumors, remains a challenging task. Clinical decision-making depends on an accurate diagnosis of the type of ovarian cancer. This study was done to evaluate the pattern of metastatic tumors to the ovary and clinical details and to analyze the survival outcomes over a period of 5 years. Patients who had metastatic tumors to the ovary are identified from the electronic database from 1 January 2015 to 30 September 2019. Clinical details are collected from the electronic charts. Survival data is collected over the phone. The total number of ovarian cancers treated during the time period was 720, of which primary high-grade mucinous tumors contributed 9 (1.2%), and metastatic tumors to ovary 70 (10%). The highest levels of CEA were seen in carcinoma rectum, colon, and cholangiocarcinoma. CA 19-9 was very high in carcinoma gall bladder, pancreas, and cholangiocarcinoma. Common primaries were stomach (23%), gall bladder (13%), and colon (13%). Adenocarcinoma with signet ring cells was found in 29% of the patients. The median follow-up was 7 months (range 1 to 40 months). The median overall survival was 10 months after diagnosis (95% CI,7.9-12.0). There was no statistically significant difference in survival between patients who had peritoneal carcinomatosis with enlarged ovaries and those who had metastasis confined to ovaries (p value 0.360). A diagnosis of metastatic tumors to the ovary is associated with a very poor prognosis and the focus of treatment should be to improve the quality of life. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s13193-020-01267-4.