Comparison of conventional diffusion-weighted imaging, diffusion kurtosis imaging and intravoxel incoherent motion in characterization of sonographically indeterminate adnexal masses.

PURPOSE: To evaluate the role of conventional diffusion weighted imaging, diffusion kurtosis imaging (DKI), and intravoxel incoherent motion (IVIM) in distinguishing benign from malignant adnexal masses. METHODS: 38 patients with 45 adnexal masses were enrolled in this prospective study and assessed with multiparametric MRI, including the IVIM-DKI sequence, on a 3 T MRI system. The mean apparent diffusion coefficient (ADC) from conventional DWI, the apparent diffusion coefficient derived from DKI (Dapp), the apparent kurtosis coefficient (Kapp), true diffusion coefficient (Dt), perfusion fraction (f) and pseudo-diffusion coefficient (Dp) were measured. RESULTS: The mean ADC, Dapp, and Dt were significantly higher in benign adnexal masses than in malignant adnexal masses (p < 0.001). f and Dp were also significantly higher in benign adnexal masses, with p values of 0.026 and 0.002, respectively. Kapp was higher in malignant masses (p < 0.001). Among mean ADC, Dapp, and Dt, mean ADC had the highest area under the curve (AUC) of 0.885. However, no statistically significant differences were observed between the ROCs of various diffusion parameters. CONCLUSION: The mean ADC, Dapp, and Kapp are useful parameters in discriminating between benign and malignant adnexal masses. Dt derived from IVIM also helps in distinguishing benign and malignant adnexal masses; however, no incremental role of IVIM and DKI over ADC could be identified in our study.

Borderline tumours of ovary and fertility preservation-Outcomes from a tertiary care center in India.

OBJECTIVE: Borderline ovarian tumors (BOT) are characterized by atypical epithelial proliferation without stromal invasion and majority are diagnosed in women of reproductive age group desirous of fertility preservation. METHODS: A retrospective review of medical records of patients diagnosed with BOT and on regular follow up at the All India Institute of Medical Sciences New Delhi, during a nine-year study period from March 2014 to March 2023 was performed. Surgical treatment was classified as radical or fertility sparing surgery (FSS). Surgical staging was defined as complete, partial or un-staged. RESULTS: Median age of 91 women was 34 years. Follow up period ranged from 4 to 222 months (median 77 months). Among 68 premenopausal women, 31 (46 %) underwent radical surgery and FSS in 37 (54 %) cases. Median time to conception in 29 women with future fertility wishes was 13 months (range, 4 to38 m). Seven of 29 cases (29 %) required ovulation induction. The pregnancy rate was 82.7 % and live birth rate was 80 %. Eight cases (8.7 %) had a recurrence (7- un-staged, 1- partially staged) and median time to recur was 36 months. There was no significant difference in recurrence between cystectomy/oophorectomy. Ovary was the site of recurrence in all surgically salvaged cases except peritoneal cavity in 1 case with mortality. Relapse free survival at 5 and 10 years in FSS and radical surgery group were similar. CONCLUSION: FSS is a safe procedure and should be considered in young patients desirous of future fertility along with a comprehensive peritoneal staging. Reproductive outcomes are excellent.

Impact of age at vaccination and cervical HPV infection status on binding and neutralizing antibody titers at 10 years after receiving single or higher doses of quadrivalent HPV vaccine.

Long-term follow-up of a cohort of unmarried girls who received one, two, or three doses of quadrivalent HPV vaccine, between 10 and 18 years of age, in an Indian multi-centric study allowed us to compare antibody responses between the younger and older age cohorts at 10-years post-vaccination, and study the impact of initiation of sexual activity and cervical HPV infections on antibody levels. Among the younger (10-14 years) recipients of a single dose, 97.7% and 98.2% had detectable binding antibody titers against HPV 16 and HPV 18 respectively at ten years post-vaccination. The proportions among those receiving a single dose at age 15-18 years were 92.3% and 94.2% against HPV 16 and HPV 18 respectively. Mean HPV 16 binding antibody titers were 2.1 folds (95%CI 1.4 to 3.3) higher in those vaccinated at ages 10-14 years, and 1.9 folds (95%CI 1.2 to 3.0) higher in those vaccinated at 15-18 years compared to mean titers seen in the unvaccinated women. Compared to previous timepoints of 36 or 48 months, binding antibodies against HPV 16 and neutralizing antibodies against both HPV 16 and HPV 18 were significantly higher at 10 years. This rise was more pronounced in participants vaccinated at 15-18 years. No association of marital status or cervical HPV infections was observed with the rise in titer. Durability of antibody response in single dose recipients correlated well with the high efficacy of a single dose against persistent HPV 16/18 infections irrespective of age at vaccination, as we reported earlier.

Cervical Cancer Screening Coverage at Tertiary Care Institutes Across India.

OBJECTIVES: The 70% screening coverage target proposed in the global cervical cancer elimination strategy is not achieved even at tertiary centres in India. A situational analysis was done to assess the currently existing facilities and barriers in tertiary care institutes. METHODS: This cross sectional multicentric study was conducted from August to September 2021 in six tertiary care institutes across India. Women aged 30-49 years attending outpatient services (OPD) were invited for cervical screening. Women and health care professionals (HCPs) were administered structured questionnaires to assess knowledge, attitude and practices regarding cervical cancer screening services. RESULTS: Out of 6709 eligible women who attended OPD, 1666 (24.8%; range:19-57%) received screening. Availability of screening kits was limited to 10-25 Pap/HPV tests per day. Visual inspection with acetic acid (VIA) and HPV testing were offered only at certain centres. Colposcopy and treatment facilities were optimal at all centres. Knowledge, attitude and practices were analysed for 1800 women: 45.7% had heard of cervical cancer, 78.0% did not know that it is preventable, 75.8% never heard about screening. Common symptoms correctly identified included postmenopausal bleeding (4.8%), postcoital bleeding (5.7%), intermenstrual bleeding (5.8%) and vaginal discharge (12.4%). Risk factors were identified by minority: poor menstrual hygiene (6.6%), oral contraceptive pill use (6.4%), multiparity (4.4%), and HPV infection (3.0%). Out of 21, mean total knowledge score (MTKS) was 2.07± 2.67. Out of 317 HCPs, 96.5% knew that cervical cancer is caused by HPV infection, is preceded by premalignant stage, and that it is preventable by screening and treatment (80.1%). Knowledge about screening modalities was present in 87.4% for cytology, 75.1% for VIA, 68.8% for HPV test. MTKS of HCPs was 20.88±6.61 out of 32. CONCLUSION: Even at tertiary centres, limited availability of HPV tests, reluctance to implement VIA and lack of awareness among women remain the major barriers.

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.

Hydrogen sulfide promotes migration of trophoblast cells by a Rho GTPase mediated actin cytoskeleton reorganization.

INTRODUCTION: Preeclampsia (PE) arises due to defective spiral artery remodelling which may be due to deficient migration of trophoblast cells. Migration of human endothelial cells has been shown to be promoted via Hydrogen sulphide(H2S)/Rho GTPase Rac1 axis. This novel role of H2S and its downstream processes have not yet been studied in the development and function of the placental trophoblast cells. METHODS: Placental tissues were obtained post-delivery from consented preeclamptic and normotensive mothers (n = 60). The protein expression levels of cystathionine-gamma-lyase (CSE) and cystathionine-beta-synthase (CBS) along with its downstream migratory molecules were compared in both the arms. The pro-migratory role of H2S was investigated in a first trimester placental cell line. RESULTS: H2S promoted the migration of trophoblast cells in a Rho GTPase dependent manner mediated by actin cytoskeleton reorganization. The reduced levels of H2S producing enzymes in the PE placentae along with decreased levels of Rho GTPases (Rac1 and Rho A) corroborate the results of PAG and AOAA treatment in down regulating the Rho GTPases in the in vitro grown placental cultures. Reduction of the migratory potential of trophoblastic cells caused due to hypoxia/reoxygenation was rescued by upregulating the H2S expression with the use of NaHS as a H2S donor. DISCUSSION: Exogenous H2S increases the migratory potential of the placental cells in culture conditions and also post hypoxia/reoxygenation injury. H2S as a gaso-transmitter holds a great potential as a therapeutic agent. Its long-term effects need to be investigated using model systems (rat/mouse) of PE following it up with clinical regulatory trials.

Expression of DKK1 in Endometrial Endometrioid Carcinoma and Its Correlation with Wnt/ß-catenin Signalling Pathway.

Objectives: Endometrial cancer is the most prevalent form of cancer affecting female reproductive organs. The most common histologic type, endometrioid carcinoma, accounts for 75-80% of all endometrial cancer cases. Studies on DKK1 expression profiles and their inhibitory role in the Wnt signalling pathway in the genesis and development of endometrial carcinoma are scarce. This study aimed to investigate DKK1 expression in endometrial carcinoma and its correlation with the Wnt/ß-catenin pathway. Methods: A total of 160 formalin-fixed paraffin-embedded samples were included in this study (50 cases of endometrial atypical hyperplasia, 50 cases of endometrioid endometrial carcinoma, 30 cases of proliferative endometrium and 30 cases of secretory endometrium). The expression patterns of DKK1, E-cadherin, ß-catenin and c-Myc in endometrial atypical hyperplasia and carcinoma were investigated and compared with that of proliferative and secretory endometrium. Immunohistochemistry and analysis were performed from July 2018 to June 2020. Results: A decreasing pattern of immunopositivity for DKK1, E-cadherin and ß-catenin from proliferative/secretory endometrium to endometrial atypical hyperplasia and endometrioid carcinoma was found. Increasing c-Myc immunopositivity was noted from proliferative/secretory endometrium to endometrial atypical hyperplasia and endometrioid carcinoma. Moreover, decreasing DKK1 immunopositivity was well correlated with E-cadherin, ß-catenin and c-Myc immunopositivity. Conclusion: Decreasing DKK1 positivity from benign endometrium to endometrioid carcinoma suggests a negative regulatory function of DKK1 in endometrioid carcinoma. DKK1 is downregulated in the Wnt signalling pathway in endometrioid endometrial carcinoma. Therefore, DKK1 is promising as a biomarker for screening endometrioid carcinoma. Future studies should examine the reactivation of the DKK1 gene, which may be a valuable strategy for antagonising the Wnt signalling pathway.

Evaluation of cervical cancer screening during pregnancy in India: Human papillomavirus testing can change the paradigm.

Background The World Health Organization's call for elimination of cervical cancer envisages 70% screening coverage of women aged 35 and 45 years by an effective test. In India, this target seems unrealistic as awareness and access to cancer prevention services are poor. However, the institutional delivery rate is now >80%. We evaluated the acceptability and feasibility of human papillomavirus (HPV) testing and its role in screening during pregnancy. Methods This observational study recruited 275 pregnant women aged >25 years between 12 and 34 weeks of gestation for screening by cytology and HPV testing. Colposcopy was advised if either test was positive. Acceptability and feasibility were assessed by a questionnaire. Results Cytology and HPV reports were available for 269 subjects. The median age was 28 years and median parity was two. Only 98 (36.4%) had heard about carcinoma cervix. Awareness improved with education (p < 0.001). On cytology, only 4 (1.5%) were abnormal (atypical squamous cells of undetermined significance 3; low-grade squamous intraepithelial lesion 1). The prevalence of high-risk HPV infection was 8.2% (22/269). On colposcopy, all had the Swede score <5. No high-grade cervical intraepithelial neoplasia or carcinoma was detected. Pre-procedure, 183 (68.0%) subjects expressed apprehension, post-procedure 114 (42.4%) of them had realized that their apprehensions were unfounded. Women found screening to be more uncomfortable after 28 weeks of gestation (n=26/68; 38.2%; p<0.001). Physicians found the cervix more difficult to visualize after 20 weeks of gestation (p<0.001). Conclusions HPV screening at 16-20 weeks of pregnancy is acceptable, feasible, and can greatly improve screening coverage in resource-limited settings. Pregnancy is a good opportunity to improve awareness of the screening programmes.

Primary leiomyosarcoma of the vulva - a rare occurrence.

Vulval tumours are rare, representing merely 4% of all gynaecological neoplasms. 98% of vulvar lesions are benign, and only 2% are malignant. Of all vulvar malignancies, while squamous cell carcinoma is the most common malignancy, leiomyosarcomas of the vulva are extremely rare. Usually these tumours have nonspecific clinical manifestations, often leading to misdiagnoses of Bartholin cysts or abscesses. We describe a case of a 47-year-old woman who presented with a nonspecific painless swelling in the left vulva for 2 months which was diagnosed as leiomyosarcoma of the vulva on biopsy as well as resection.

Robert's Uterus versus Juvenile Cystic Adenomyoma - Diagnostic and Therapeutic Challenges - Case Report and Review of Literature.

This case report highlights the diagnostic dilemma and therapeutic challenges encountered while managing adolescent girls with progressive dysmenorrhoea and management of Robert's uterus. Two girls aged 20 years and 13 years presented with severe progressive dysmenorrhoea. In the first case, laparoscopy revealed juvenile cystic adenomyoma (JCA) of 3 cm × 3 cm on the left side anteroinferior to the round ligament. Laparoscopic resection of the lesion was done, and histopathology revealed features of adenomyosis. In the second case, there was a globular enlargement of the right half of the uterine body with round ligament and adnexa attached to the lesion (Robert's uterus). In view of severe symptoms, complete resection of the lesion and partial resection of hemi-uterus was done, followed by myometrial defect closure. Both cases were initially diagnosed as JCA, and the final diagnosis was made on laparoscopy. Both girls had complete symptomatic relief from the next menstrual cycle and have been under follow-up for 24 months and 18 months, respectively. Due to the rarity of conditions, Robert's uterus and JCA are usually misdiagnosed with each other or with other Mullerian anomalies such as a non-communicating unicornuate uterus. Radiologists and clinicians should be aware of these different pathologies causing similar symptoms. Understanding the pathology, early diagnosis, timely referral and correct surgical procedure are emphasised to improve reproductive outcomes.

Augmenting the Angiogenic Profile and Functionality of Cord Blood Endothelial Colony-Forming Cells by Indirect Priming with Bone-Marrow-Derived Mesenchymal Stromal Cells.

Cellular therapy has shown promise as a strategy for the functional restoration of ischemic tissues through promoting vasculogenesis. Therapy with endothelial progenitor cells (EPCs) has shown encouraging results in preclinical studies, but the limited engraftment, inefficient migration, and poor survival of patrolling endothelial progenitor cells at the injured site hinder its clinical utilization. These limitations can, to some extent, be overcome by co-culturing EPCs with mesenchymal stem cells (MSCs). Studies on the improvement in functional capacity of late EPCs, also referred to as endothelial colony-forming cells (ECFCs), when cultured with MSCs have mostly focused on the angiogenic potential, although migration, adhesion, and proliferation potential also determine effective physiological vasculogenesis. Alteration in angiogenic proteins with co-culturing has also not been studied. We co-cultured ECFCs with MSCs via both direct and indirect means, and studied the impact of the resultant contact-mediated and paracrine-mediated impact of MSCs over ECFCs, respectively, on the functional aspects and the angiogenic protein signature of ECFCs. Both directly and indirectly primed ECFCs significantly restored the adhesion and vasculogenic potential of impaired ECFCs, whereas indirectly primed ECFCs showed better proliferation and migratory potential than directly primed ECFCs. Additionally, indirectly primed ECFCs, in their angiogenesis proteomic signature, showed alleviated inflammation, along with the balanced expression of various growth factors and regulators of angiogenesis.

COVID-19 as a catalyst for reimagining cervical cancer prevention.

Cervical cancer has killed millions of women over the past decade. In 2019 the World Health Organization launched the Cervical Cancer Elimination Strategy, which included ambitious targets for vaccination, screening, and treatment. The COVID-19 pandemic disrupted progress on the strategy, but lessons learned during the pandemic - especially in vaccination, self-administered testing, and coordinated mobilization on a global scale - may help with efforts to achieve its targets. However, we must also learn from the failure of the COVID-19 response to include adequate representation of global voices. Efforts to eliminate cervical cancer will only succeed if those countries most affected are involved from the very start of planning. In this article we summarize innovations and highlight missed opportunities in the COVID response, and make recommendations to leverage the COVID experience to accelerate the elimination of cervical cancer globally.

An unusual association of type II Mayer-Rokitansky-Kuster-Hauser syndrome, turner mosaic syndrome and tubo-ovarian inguinal hernia- case report and review of literature.

BACKGROUND: Herniation of ovaries and Mullerian structures into inguinal canal is usually reported in infants and is rare among adults. We are presenting a rare case of Mullerian agenesis and Turner mosaic syndrome with tubo-ovarian inguinal hernia. CASE PRESENTATION: A 17-year-old girl presented with complaints of primary amenorrhea, phenotypical features of Turner syndrome with left inguinal hernia and severe hypertension. Baseline hormonal analysis was normal. Karyotype revealed Turner mosaic with 46XX (85%); 45XO (15%). MRI showed Mullerian agenesis with normally located right ovary in pelvis and left ovary prolapsed through deep inguinal ring into the canal of Nuck. Anti-hypertensives were started and patient optimized for surgery. Laparoscopic hernia repair and repositioning of left ovary into the pelvis was done. Patient had uneventful post-operative course and was discharged in stable condition on anti-hypertensive medication. Future reproductive issues and need of passive vaginal dilatation or vaginoplasty before marriage were explained to the patient and family. CONCLUSION: This is the first ever reported case with unusual association of atypical MRKH, Turner mosaic syndrome and tubo-ovarian hernia into the inguinal canal. The case emphasizes the need and importance of complete work up of these atypical cases as patients may have more than one cause of primary amenorrhea and complete evaluation is must before any medical or surgical intervention.

Evaluation of immune response to single dose of quadrivalent HPV vaccine at 10-year post-vaccination.

BACKGROUND: The recent World Health Organization recommendation supporting single-dose of HPV vaccine will significantly reduce programmatic cost, mitigate the supply shortage, and simplify logistics, thus allowing more low- and middle-income countries to introduce the vaccine. From a programmatic perspective the durability of protection offered by a single-dose will be a key consideration. The primary objectives of the present study were to determine whether recipients of a single-dose of quadrivalent HPV vaccine had sustained immune response against targeted HPV types (HPV 6,11,16,18) at 10 years post-vaccination and whether this response was superior to the natural antibody titres observed in unvaccinated women. METHODS: Participants received at age 10-18 years either one, two or three doses of the quadrivalent HPV vaccine. Serology samples were obtained at different timepoints up to 10 years after vaccination from a convenience sample of vaccinated participants and from age-matched unvaccinated women at one timepoint. The evolution of the binding and neutralizing antibody response was presented by dose received. 10-year durability of immune responses induced by a single-dose was compared to that after three doses of the vaccine and in unvaccinated married women. RESULTS: The dynamics of antibody response among the single-dose recipients observed over 120 months show stabilized levels 18 months after vaccination for all four HPV types. Although the HPV type-specific (binding or neutralizing) antibody titres after a single-dose were significantly inferior to those after three doses of the vaccine (lower bounds of GMT ratios < 0.5), they were all significantly higher than those observed in unvaccinated women following natural infections (GMT ratios: 2.05 to 4.04-fold higher). The results correlate well with the high vaccine efficacy of single-dose against persistent HPV 16/18 infections reported by us earlier at 10-years post-vaccination. CONCLUSION: Our study demonstrates the high and durable immune response in single-dose recipients of HPV vaccine at 10-years post vaccination.

Central nervous system metastasis from epithelial ovarian cancer- predictors of outcome.

Management of central nervous system (CNS) metastases from epithelial ovarian cancer (EOC) is an unmet need. We analyzed data on 41 such patients to evaluate predictors of outcome. Between January, 2010 and December 2020, among 1028 patients with EOC treated at our institute 41 (3.98%) developed CNS metastasis. Median age of patients was 48 years, ranging from 22 to 75 years. Primary outcome measure was progression free survival (PFS). Overall survival (OS), and analysis of prognostic factors were secondary outcome measures. An intention to treat analysis was done. We also performed review the literature (n=2253) as regards to clinicopathological and radiological features, treatment received, survival outcomes and prognostic factors. Median time from diagnosis of EOC to CNS metastasis was 27 months (range: 0 to 101 months). 33(80.5%) patients had FIGO stage III-IV at baseline and serous carcinoma (75.6%) was common pathology subtype. Thirteen (31.7%) patients had isolated CNS metastasis and 28 (68.3%) had intra-abdominal disease in addition. Nineteen (46.3%) patients achieved complete response post treatment with surgery, radiation and chemotherapy. Median PFS and OS from the time of CNS metastasis is 12 (range:1 to 51) months and 33 (range: 1 to 71) months, respectively. Absence of extracranial disease and lower serum CA-125 at diagnosis of CNS metastasis were predictive of superior PFS and OS on multivariate analysis. CNS metastasis is a late event in EOC, post multiple lines of treatment. Patients with disease limited to brain and treated with surgical resection and chemoradiation have best outcome.

Role of Positron Emission Tomography/Computed Tomography in Epithelial Ovarian Cancer.

Ovarian cancer (OC) is the most lethal gynecological malignancy with majority of cases diagnosed in advanced stages and associated with high morbidity and mortality. Positron emission tomography/computed tomography (PET/CT) has emerged as an integral part of the management of several nongynecological cancers. We used PubMed search engine using MeSH words "ovarian cancer" and "PET/CT" and reviewed the current status of PET/CT in epithelial OC. Its application related to ovarian tumor including adnexal mass evaluation, baseline staging, as a triaging tool for upfront surgery or neoadjuvant chemotherapy, for response assessment and prognostication, and for relapse detection and treatment planning has been highlighted. we highlight the current guidelines and newer upcoming PET modalities and radiotracers.

Surgical Outcomes and Feasibility of Transvaginal Sacrospinous Ligament Fixation through Anterior Approach for Women with Pelvic Organ Prolapse.

Introduction: Supporting vaginal vault or apex is a central component of primary therapy and to prevent recurrence of prolapse. This study aims to review the surgical outcomes and feasibility of the anterior approach following both sacrospinous fixation (SSF) and sacrospinous hysteropexy (SSHP) in a single center over a specific period. And also to review its impact on quality of life. Materials and Methods: This was a retrospective study that included all women who underwent unilateral SSF or SSHP through anterior approach for pelvic organ prolapse (POP) from May 2021 to May 2023 after institutional ethical approval for the study. The anterior approach was undertaken in 47 patients which were included in final review. A retrospective case note review to assess urinary symptoms was undertaken at baseline and 3 months by urinary distress inventory 6 score. The main outcome measure was recurrence of prolapse, predominant compartment for prolapse, presenting complaints, concomitant surgeries performed, and associated urinary complaints. Results: The mean age was 56.17 ± 11.95 years and the average body mass index was 26.12 ± 3.11 kg/m2. Except for 4 cases of SSHP, remaining women were postmenopausal at the time of surgery. Ten women presented with urinary complaints as their chief complaint. On examination, POP Quantification evaluation, 35 cases have Ba as leading point, 10 have Ap as their leading point and in two cases C was the leading point. Conclusion: Anterior unilateral sacrospinous ligament fixation is a safe, effective strategy to treat POP and other concomitant surgery can also be well combined with it.

Can portable Colposcopes Replace Standard-of-care Colposcopes? A Crossover Trial of Two Portable Colposcopes with a Standard-of-Care Video Colposcope.

BACKGROUND: Screen positive women need to be triaged by colposcopy which is a major challenge in low-middle income countries. Portable colposcopes may overcome many challenges, reduce referrals and enable a single visit approach. This study assessed the performance of portable colposcopes and potential to reduce referral. METHOD: This crossover randomised study enrolled women aged 25 to 65 years with abnormal screening result or cervical symptoms. All women underwent visual inspection with acetic acid (VIA), HPV test, colposcopy with two portable colposcopes (Gynocular®, Gynius, Sweden, and Pocket® transvaginal colposcope, Duke University, NC, USA) and a standard video colposcope, and biopsy. Colposcopic Swede score agreement between portable and video colposcopes, as well as agreement of Swede score with histology were calculated for each device. The potential impact of portable colposcopes in a single visit approach was assessed based on the final diagnosis. RESULTS: Among 250 subjects, 27(10.80%) had high-grade cervical intraepithelial neoplasia (CIN2+) lesions. Swede scores for Pocket and Gynocular colposcopes were similar to video colposcope in 248 (99.20%) and 247 (98.80%) subjects, respectively (agreement scores 0.9969 and 0.9954, respectively). At a Swede score cut-off of ≥5, all three devices had identical sensitivity, specificity, positive and negative predictive value of 96.30%, 92.30%, 60.50% and 99.50,. Ablative treatment offered at field setting would result in optimal treatment in 52.0% and 85.1% cases when screened with VIA and HPV test respectively; using Pocket colposcope could improve this to 94.0% and 95.9%, respectively. Overtreatment and referral rates reduced from 46.8% and 12.4% to 4.8% and 6.0%, respectively, when VIA test is followed by triage with pocket colposcope. These outcomes were comparable to screening with HPV followed by colposcopy triage. CONCLUSIONS: Pocket colposcope performed comparably to the video colposcope. Used by healthcare providers in the field setting, they can augment the results of VIA significantly.

Prognostic Significance of HE4 Tissue Expression in Serous Epithelial Ovarian Carcinoma.

Neerja BhatlaBackground Human Epididymis protein 4 (HE4) is expressed in ovarian cancer. Preoperative serum testing is still not widely available. This pilot study aimed to investigate the magnitude of expression of HE4 in tissue sections of serous epithelial ovarian carcinoma, its correlation with clinical outcome, and the feasibility of HE4 immunohistochemistry as a prognostic marker. Materials and Method In this ambispective study, immunohistochemistry (IHC) was used to evaluate tissue sections of ovarian serous epithelial carcinoma at primary cytoreductive surgery. On HE4 immunohistochemistry (IHC), the magnitude of HE4 expression was assessed categorically as high or low HE4 expression and semiquantitatively by the H-score, and correlated with clinical outcome in terms of survival status, progression-free survival, and overall survival. Results Of 32 cases, most ( n = 31, 96.8%) were positive for HE4 IHC. The mean age was 49 ± 8.2 years; 29 (90.6%) patients were in FIGO stage IIIC; 25 (78.9%) had ≥1cm residual disease after surgery; 31 (96.8%) received adjuvant chemotherapy, either 3-weekly ( n = 25, 81.2%) or dose-dense weekly ( n = 6, 18.8%) regimen. The majority ( n = 31, 96.8%) had a high-grade tumor, of whom 19 (59.4%) had high HE4 expression and 13(40.6%) patients had H-score in the range of 5 to 8. The mean H-score was 6.97 ± 3.61 (range 0 to 12). The overall survival of the study population at 64 months was 36.65% (95% CI: 8.59-66.34), with median overall survival of 59 months. A new scoring system was developed combining categorical HE4 expression and serum CA-125 levels; the combination of HE4 expression with postoperative CA-125 levels was found to be the best prognostic marker for overall survival ( p = 0.05). A composite score of 2 identified patients with poor progression-free survival (HR 4.64, p = 0.039) and overall survival (HR 5.45, p = 0.05). Conclusion The new composite scoring system using HE4 IHC with postoperative serum CA-125 levels offers an extremely useful option for prognosticating patients with serous epithelial ovarian carcinoma than serum CA-125 alone. This is useful where preoperative records are not available to the treating clinician.

Awareness, perceptions, and choices of physicians pertaining to human papillomavirus (HPV) vaccination in India: A formative research study.

Introduction: India accounts for one-fifth of the global burden of cervical cancer cases and mortality. A safe and effective vaccine to prevent human papillomavirus (HPV) infections, the primary cause of cervical malignancies, is available in India but multiple barriers lead to its low uptake in the country. Physicians are a key stakeholder and communicator in the Indian health system and have the potential to increase HPV vaccine uptake. Objective: We undertook formative research to understand awareness, perceptions and choices of physicians when recommending the HPV vaccine to parents of adolescent girls. Methods: We conducted in-depth interviews with 32 physicians in two districts of West Bengal. Data collection was carried out between July and August 2019. The data was transcribed, coded, and analyzed using NVivo software using the thematic analysis technique. Results: Our findings suggest that while physicians are generally aware about the burden of cervical cancer and its prevention by HPV vaccination, they face several barriers to recommending the HPV vaccine routinely and strongly. These include the lack of national-level guidance on the age eligibility and dosage, lack of practice-level opportunities such as well or non-sick visits and other routine adolescent vaccines, practice-level barriers like out-of-pocket cost and vaccine availability, and perceived parental hesitancy arising from reluctance to discuss cervical cancer, its prevention, and HPV vaccination. Conclusions: Physicians in our study exhibited hesitancy when recommending the HPV vaccine. They also faced logistical barriers. It is important that the barriers pertaining to when and how physicians recommend the vaccine be tackled through further education, policy change, and development and implementation of interventions that are evidenced-based.