Genetic Variations Affect Chemotherapy Outcomes: A Role of the Spindle-assembly Checkpoint.

Cancer patients suffer from complicated chemotoxicity. Pharmacogenomics can help stratify patients by predicting their response to treatment and susceptibility toward severe side effects. The spindle-assembly checkpoint (SAC) is an important pathway that is activated by platinum and taxane compounds and plays a crucial role in their cytotoxic activity. This study investigated a SAC component, Budding Uninhibited by Benzimidazoles 3 (BUB3), its expression, and genetic variants in advanced ovarian cancer patients treated with paclitaxel-carboplatin chemotherapy. Among 80 patients, BUB3 expression correlated with chemosensitivity, suggesting its potential as a predictive marker for chemotherapy response. However, high BUB3 expression was associated with a higher risk of poor survival. In addition, genetic polymorphisms in BUB3 (rs11248416 and rs11248419) were significantly linked to chemotherapy-related toxicities, with rs11248416 showing a negative impact on the patient's physical quality of life.

Assessment of quality of life among advanced ovarian cancer patients in a tertiary care hospital in India.

PURPOSE: The study aims to record the quality of life (Qol) and its changes while ovarian cancer (OC) patients undergo debulking surgeries and chemotherapy in a tertiary care hospital of Eastern India. METHODS: Patients with advanced epithelial OC (FIGO stages III-IV) were recruited. They underwent primary/interval debulking surgeries with classical chemotherapy (adjuvant/neoadjuvant) of intravenous tri-weekly doses of paclitaxel + carboplatin. QoL was assessed using Fact- O + FACIT-Sp-12 questionnaire with a set of 51 questions in different domains (spiritual, physical, social, emotional, and functional factors) and a special set for OC patients under the heading "Additional concerns." The responses from patients were recorded at baseline (diagnosis/study entry), 2, 4, and 6 months during the treatment visits. Overall survival (OS) was assessed using Kaplan Meier curve. RESULTS: A majority of patients were 49.15±10.8 years of age, school-educated (54%), unemployed/homemakers (73.5%), belonging from rural setup (64.6%) with a monthly income of Rs. 2000/- to Rs. 5000/-. There was no statistically significant (p>0.05) improvement found in Qol from the baseline till the end of the study, neither overall nor in subsets (responders (Rs)/partial responders (PRs)/non-responder (NRs) groups or the adjuvant and neoadjuvant chemotherapy groups). The common toxicities like anemia, constipation, and weight loss were significantly (p<0.05) correlated with the patients' physical, functional, emotional, and social well-being. CONCLUSION: Ovarian cancer patients represent a poor functional, social, and disease-specific quality of life that needs to be addressed, identified, and improved by the growing nexus of healthcare providers and researchers.

Correlation Between p16/Ki-67 Expression and the Grade of Cervical Intraepithelial Neoplasias.

Interpretation of histopathology of cervical premalignant lesions suffers from marked interobserver variability due to its subjective nature. We aimed to evaluate the usefulness of the biomarkers p16 and Ki-67 in improving the diagnostic accuracy of cervical histopathology and assess the correlation between p16 expression and human papillomavirus test in different grades of cervical intraepithelial neoplasia (CIN). Cervical tissue specimens with a diagnosis of CIN 1 or worse (CIN 1+) on hematoxylin and eosin staining were selected for immunohistochemistry (IHC) staining for p16 and Ki-67. The IHC slides were examined by a gynecologic pathologist along with a review of hematoxylin and eosin slides. The review histopathology diagnosis was used to correlate with the IHC results. We observed that the proportion of women with overexpression of p16 increased with increasing histologic severity: 0% in women with normal histology; 33.3% in women with CIN 1; 58.1% in women with CIN 2; and 73.8% in women with CIN 3. Among the human papillomavirus-positive women, 76.3% (58/76) women with CIN 2/CIN 3 expressed p16, and only 8.9% (4/45) women with normal histopathology or CIN 1 expressed the same. A combination of p16 positivity and abnormal expression of Ki-67 beyond the lower third of the epithelium was observed in 0% of normal/CIN 1 and 60.5% (40/66) of CIN 3 detected on routine histopathology. We concluded that dual staining could be used as an adjunctive test to improve the diagnostic accuracy of histopathology. In addition, p16/Ki-67 IHC has a role in guiding management decisions in cases with discordant colposcopy and histopathology diagnoses.

A Study of the Impact and Restitutive Efforts of Cervical Cancer Screening during the COVID-19 Pandemic in a Regionsl Cancer Centre in Eastern India.

AIM: To evaluate the feasibility and efficacy of switching to a self-sampling based screening as compared to ongoing provider-collection based screening using HPV DNA test and assess the compliance of HPV positive women for further treatment during the COVID 19 pandemic. METHOD: The study participants were women aged 30-60 years from rural and semi-urban communities around Kolkata, who underwent screening followed by HPV testing by Hybrid Capture II test. In the pre pandemic era, the women who attended the health centres where trained health workers that collected cervical samples. Following lockdown, the health workers distributed the self-sampling device to the women during home visits and counselled them to collect their samples by themselves. Thereafter the self collected screened positive women were brought to the hospital for further treatment instead of community clinics. RESULTS: From April 2018 to March 2020, 12,718 women underwent screening using either HPV DNA test or visual inspection with acetic acid. HPV samples were either provider collected (62.7%) or self-collected (37.2%). The HPV positivity and CIN2+ detection rate were 5.4% and 2%. From April 2020 to February 2022, 10,792 women underwent screening using self-sampling only. The HPV positivity rate and CIN2+ detection rate were found to be 5.1% and 1.9 % . CONCLUSION: Cervical cancer screening by HPV self-sampling advocates participation of more women especially in rural areas, while accelerating progress towards elimination of cervical cancer.

Terminally Exhausted CD8+ T Cells Resistant to PD-1 Blockade Promote Generation and Maintenance of Aggressive Cancer Stem Cells.

SIGNIFICANCE: Cross-talk with TTEX CD8+ T cells mediated by the VEGFR2 axis induces aggressive properties in cancer stem cells to promote tumor progression.

Understanding the Correlation between Metabolic Regulator SIRT1 and Exosomes with CA-125 in Ovarian Cancer: A Clinicopathological Study.

Background: Ovarian cancer (OvCa), the deadliest gynaecological malignancy, is associated with poor prognosis and high mortality rate. Ovarian cancer has been related with CA-125 and metabolic reprogramming by SIRT1 leading to metastasis with the involvement of exosomes. Methods: Clinicopathological data of OvCa patients were collected to perform the analysis. Patients' samples were collected during surgery for immunohistochemistry and flow cytometric analysis of SIRT1, HIF-1α, exosomal markers (CD81 and CD63), ki-67, and PAS staining for glycogen deposition. Adjacent normal and tumor tissues were collected as per the CA-125 levels. Results: CA-125, a vital diagnostic marker, has shown significant correlation with body mass index (BMI) (P = 0.0153), tumor type (P = 0.0029), ascites level, ascites malignancy, degree of dissemination, tumor differentiation, FIGO stage, TNM stage, laterality, and tumor size at P < 0.0001. Since significant correlation was associated with BMI and degree of dissemination, as disclosed by IHC analysis, metabolic marker SIRT1 (P = 0.0003), HIF-1α (P < 0.0001), exosomal marker CD81 (P < 0.0001), ki-67 status (P = 0.0034), and glycogen deposition (P <0.0001) were expressed more in tumor tissues as compared to the normal ones. ROC analysis of CA-125 had shown 327.7 U/ml has the best cutoff point with 82.4% sensitivity and specificity of 52.3%. In addition, Kaplan-Meier plots of CA-125 (P < 0.0001), BMI (P = 0.001), degree of dissemination (P < 0.0001), and ascites level (P <0.0001) reflected significant correlation with overall survival (OS). Upon multivariate Cox-regression analysis for overall survival (OS), BMI (P = 0.008, HR 1.759, 95% CI 1.156-2.677), ascites malignancy (P = 0.032, HR 0.336, 95% CI 0.124-0.911), and degree of dissemination (P = 0.004, HR 1.994, 95% CI 1.251-3.178) were significant proving to be independent indicators of the disease. Conclusion: Clinicopathological parameters like BMI, degree of dissemination, and ascites level along with CA-125 can be prognostic factors for the disease. Levels of CA-125 can depict the metabolic and metastatic factors. Thus, by targeting SIRT1 and assessing exosomal concentrations to overcome metastasis and glycogen deposition, individualized treatment strategy could be designed. In-depth studies are still required.

Evaluation of numerical rating scale and neuropathic pain symptom inventory pain scores in advanced ovarian carcinoma patients undergoing surgery and first-line chemotherapy.

BACKGROUND AND AIM: Advanced epithelial ovarian cancer (OC) has a high disease manifestation with difficult-to-manage symptoms that limit the patients' functionality. Abdominal pain, persistent back pain, and neuropathic pain are among the common discomforts associated with OC and its treatment. Our study aims to determine pain scores in advanced OC patients undergoing surgery and chemotherapeutic treatment with carboplatin and paclitaxel. METHODS: One hundred and ten patients with advanced epithelial OC were enrolled and treated with surgery and an adjuvant/neoadjuvant chemotherapy regimen of carboplatin-paclitaxel for six cycles (triweekly). Pain intensity was analyzed using the validated numerical rating scale for resting, movement, sleep interference-associated pain, and neuropathic pain scores were evaluated using the neuropathic pain symptom inventory scale. Pain was correlated with Qol according to Fact-O questionnaires. Chemo-response was evaluated using the CA125 blood biomarker and CT scan of the abdomen and thorax. Data were recorded at baseline, 2, 4, and 6 months of the six chemotherapy cycles. RESULTS: Of the 110 patients, no statistically significant differences were found in pain at baseline and after treatment (P > 0.05) and between the responder and non-responder categories (P > 0.05). However, movement-associated pain had a significant correlation with chemo-response and a strong positive correlation with the patients' physical and functional wellbeing. There were more chemo-induced neuropathy occurrences (P = 0.001) in the neoadjuvant chemotherapy group. CONCLUSION: Patients in the neoadjuvant chemotherapy arm experienced more chemo-induced neuropathy that was persistent and did not improve with the treatment. RELEVANCE FOR PATIENTS: Peripheral neuropathy is a common adverse effect of platinum and taxane chemotherapeutic drugs that persists throughout cancer treatment and in survivorship. This research provides evidence that chemotherapy-associated neuropathy affects Qol of patients and it will be helpful to improve pain and palliative care management policies.

Experience of Human Papillomavirus Vaccination Project in a Community Set Up-An Indian Study.

BACKGROUND: Initial introduction of HPV vaccination from 2006 to 2008 was largely confined to high-income countries (HIC), such as Australia, the United States, and Europe, where cervical cancer incidence is lowest. Much of the post-introduction literature has come from HICs, with a focus on coverage levels achieved, provider acceptability and early impact of vaccination on disease endpoints. However, there are a few literature evaluating the mechanics of delivery, feasibility of the health system and acceptability from low and middle income countries (LMICs). The primary objective was to evaluate the feasibility, acceptability and safety of two dose HPV vaccination in adolescent girls between 9-14 years. METHODS: After an orientation camp followed by filling up of prevaccine questionnaires by parents on HPV related diseases and its vaccines and informed consent, girls between9-14years were vaccinated. They were asked to report any side effects in the next 24 hours after each dose. Parents were contacted on Day 7 and Day 30 to enquire about any side effects . Total 3 visits were required i.e two for the vaccination and one visit at 7th month post completion of second dose. To estimate the acceptability, successful completion of two doses by at least 80% of the girls were measured. For measurement of acceptability, either of the parents were recalled along with their daughter at 7th month and were asked to fill up a pre-set questionnaire. RESULTS: After institutional ethical clearance, 555 girls were recruited in the study from rural parts of West Bengal, India between July, 2017 to November, 2017. Out of which, 544 girls (98%) received their 2nd dose between January, 2018 and May, 2018 without any serious adverse effects. No serious adverse effect was reported on follow up till December, 2019. CONCLUSION: The introduction of HPV vaccination is feasible in large scale and the vaccine is well accepted and safe.
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Sociodemographic factors and clinical presentation of women attending Cancer Detection Centre, Kolkata for breast examination.

BACKGROUND: Breast cancer is the most common cancer in Indian women. AIM: The aim of the study was to report the sociodemographic factors, habits, personal history, gynecological and obstetric history, the clinical presentation of Indian women, and analyze those factors with the diagnosis of breast cancer. METHODS: This study is based on retrospective data collection from case files of women who attended the Cancer Detection Centre during January1995-September 2016. RESULTS: Data analysis for 1196 women showed 31.5% aged between 26 and 35 years; 90.7% were Hindus; 61.3% school-educated; 77.0% housewives/unemployed; 80.6% married and 98.2% were non-vegetarian. Physical activity, medical history and gynecologic history of menarche, menstrual type, menopause, marital age, and breast feeding history had a strong correlation with clinical diagnosis (p<0.05). About 8.4% of the total population was diagnosed with breast cancer using smear cytology, FNAC, mammography, and USG. CONCLUSIONS: Age, lack of proper education, marital status, food habit, physical activity, age of menarche, menstrual type, menopause, marital age, and breastfeeding history were highlighted as significant risk factors of breast cancer in Indian women. Smears from nipple discharges, FNAC, mammography, and USG are effective methods for breast cancer detection in low-cost setting where routine organized screening programs are not available. RELEVANCE FOR PATIENTS: The study will identify important risk factors among women in the Eastern region of India. Thus, background information of patients can be used to emphasize the importance of organizing breast cancer screening while making public health policies and implementing breast cancer control programs.

Unscarred Uterine Rupture: A Retrospective Analysis.

INTRODUCTION: Uterine rupture is a catastrophic obstetrical emergency associated with a significant feto-maternal morbidity and mortality. Many risk factors for uterine rupture, as well as a wide range of clinical presentations, have been identified. OBJECTIVES: To analyze the frequency, predisposing factors, and maternal and fetal outcomes of uterine rupture. METHODS: A retrospective analysis of cases of unscarred uterine rupture was conducted at the Department of Obstetrics and Gynecology, RIMS, Imphal from June 1, 2010 to June 30, 2012. RESULTS: Our analysis comprised 13 cases. Of these, 30.8 % were booked cases. Most of the cases (46.2 %) were Para 2. Uterine rupture occurred at term in 10 cases. The rupture occurred due to mismanaged labor (30.8 %), the use of oxytocin (23 %), instrumental delivery (15.4 %), obstructed labor (15.4 %), induction by prostaglandin gel (7.7 %), and placenta percreta (7.7 %). Maternal deaths and perinatal deaths were 30.8 and 53.8 %, respectively. Sub-total hysterectomy was done in 8 cases and in 1 patient laparotomy with repair was performed. CONCLUSION: Ruptured uterus causes a high risk in patients. An unscarred uterus can undergo rupture even without etiological or risk factors. The patients with mismanaged labor, grand multiparas, and obstructed prolonged labor must be managed by properly trained personnel at a tertiary care center in order to avoid the morbidity or mortality.