High prevalence of "non-pathogenic" POLE mutation with poor prognosis in a cohort of endometrial cancer from South India.

OBJECTIVE: The Cancer Genome Atlas (TCGA) project identified favorable prognosis regarding the ultra-mutated endometrial cancer (EC) subtype linked to polymerase epsilon gene (POLE) mutations. This study investigated POLE mutations in EC of Indian patients. METHODS: This retrospective analytical study was conducted between January 2016 and January 2023 at the Government Medical College, Kozhikode, and the MVR Cancer Center, Kozhikode, Kerala. Sanger sequencing of POLE gene exons 9 and 13 in 151 EC patients was carried out to analyze the relationship between mutations and epidemiological factors, clinicopathologic features, and treatment outcomes. RESULTS: Among 151 cases enrolled, 39 were unique POLE-mutated cases. Significant associations were high-grade tumors, myometrial invasion >50%, and Lymph-vascular space invasion (LVSI). The median follow-up was 40 months (95% confidence interval [CI], 34-46). A lower mean disease-specific survival (DSS) of 51.7 months (95% CI, 43.7-59.6) was noted in the POLE-mutated group compared with 72.11 months (95% CI, 67.60-76.62) for the POLE wild-type. A statistically significant hazard ratio (HR) of 2.683 for DSS in the POLE-mutated group was noted. In advanced stages (FIGO stages II-IV), a nine-fold HR for DSS and overall survival (OS) compared with POLE wild-type was identified. After controlling for treatment effects using Cox proportional HR, advanced-stage POLE-mutated tumors had a significantly higher HR of 8.67 for DSS compared with POLE-wild-type tumors of the same stage. CONCLUSION: This study identified a unique set of POLE mutations in Indian EC patients associated with poor prognosis, which were particularly pronounced in advanced stages. Advanced stage of presentation, type of POLE mutations, and possibly ethnicity are predictors of adverse outcomes in POLE-mutated EC. The present study highlights ethnicity as a determinant of phenotypic expression of genetic change.

A Review of Commonly used Health-Related Quality of Life instruments in Gynecological Cancer Survivors.

The number of cancer survivors is increasing steadily due to an aging population, continuing improvement in early detection, and treatment. Comparative effectiveness studies and clinical trials are being done to assess late effects of treatment and health-related quality of life. This is in addition to long-term follow-up to assess survival. The aim of the review was to summarize the literature on commonly used quality of life instruments for patients with gynecological cancers with special focus on patient reported outcomes. A literature review was done to summarize the commonly used health-related quality of life instruments in gynecological cancer survivors. Most items assess general quality of life, sexual function, and/or treatment-related toxicity. The commonly reported instruments are the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ C30) with disease specific modules for cervix, ovary, and endometrium. Another tool is the Functional Assessment of Cancer Therapy (FACT) questionnaire with similar disease specific modules. The questionnaires were accessed with permission from these organizations. These instruments typically have about 10-30 questions that assess treatment related bowel and bladder toxicity. This is connected to the patients' self-reported quality of life, generally ranked using a 5-point scale. Length and emphasis vary in different questionnaires. The validated tools in cancer populations allow better quantification and assessment of quality of life. However, there may be limitations. Some of the general instruments may be too broad to assess treatment-related long-term side effects. Others may be too narrow to generalize closely related patient groups. Also, some questions may not be culturally appropriate in certain situations.

Comparison of two self-sampling methods for human papillomavirus (HPV) DNA testing among women with high prevalence rates.

One major advantage of molecular assays for human papillomavirus (HPV) DNA detection is that these assays can be performed on self-collected samples unlike cytology or visual inspection with acetic acid (VIA). This cross-sectional study was carried out between March 2017 and April 2019 to compare the diagnostic performance in self-collected urine and vaginal samples for HPV DNA detection. Viral DNA was extracted from processed samples using a Qiagen viral DNA extraction Kit (QIAamp DNA Mini Kit). To detect four common high-risk HPV types (16, 18, 31, 45), multiplex real-time polymerase chain reaction (PCR) targeting the LCR/E6/E7 region of the HPV genome was performed in ABI 7500 cycler (Applied Biosystems). The negative samples were screened by conventional PCR targeting the L1 capsid region to exclude other HPV types. The overall agreement between the two self-collecting sampling methods was 64.04% with a κ value of 0.29 pointing towards a fair agreement (P < .01). The sensitivity of HPV DNA detection in urine samples was 57.95% (47.52%, 67.72), and specificity was 84.6% (66.47%, 93.85%) when compared with vaginal samples. The study concludes that self-collected vaginal HPV DNA testing is more sensitive than unpreserved-urine samples for HPV DNA detection in a hospital-based setting.

Diagnostic accuracy of self-collected vaginal samples for HPV DNA detection in women from South India.

OBJECTIVES: To assess the efficacy of self-collected vaginal samples compared with physician-collected cervical samples for the detection of HPVDNA. METHODS: A hospital-based cross-sectional study was carried out among patients with newly diagnosed cervical cancer attending the Gynecologic Oncology Division, Department of Obstetrics and Gynecology and Radiation Oncology Department at Government Medical College, Kozhikode, Kerala between March 2017 and April 2019. Consenting patients collected their vaginal samples, followed by cervical sample collection by the clinician. The paired samples were transported at 4-8 °C to the laboratory. Amplification of LCR/E6/E7 regions of the HPV genome was done by polymerase chain reaction (PCR). The agreement level between paired samples was assessed by the Kappa index. RESULTS: Among the 114 cervical cancer patients enrolled in the present cross-sectional study, the prevalence of HPV DNA was 78.1% (95% confidence interval [CI] 69.2%-85%) in cervical samples and 77.2% in vaginal samples (95% CI 68.7%-83.9%). The overall agreement between the two sampling methods was 93.9% and the kappa value was 0.82 (P<0.001). The sensitivity of HPV detection using vaginal samples was 98.9% (95% CI 93.9%-99.8%) and the specificity was 100% (95% CI 86.7%-100%) with cervical sampling as the gold standard. By Kappa index, an almost perfect agreement for HPV DNA detection between self-collected and physician-collected samples was observed. CONCLUSION: Self-collection of vaginal samples ensures equity of cervical cancer screening in low-income countries such as India.

Human papillomavirus (HPV) DNA detection in uterine cervix cancer after radiation indicating recurrence: a systematic review and meta-analysis.

OBJECTIVE: The causal association of human papillomavirus (HPV) in uterine cervical cancer was well established and this oncogenic virus was reported to be a biomarker for overall recurrence and central pelvic recurrence. The objective of the present systematic review and meta-analysis was to assess the role of HPV DNA testing in early detection of recurrence among cervical cancer survivors after radiotherapy. METHODS: We performed a systematic review and meta-analysis by means of searching electronic databases for published articles between January 1984 and June 2018, on the basis of standard systematic review guidelines prescribed by major agencies namely Cochrane Collaboration (https://www.cochrane.org) and Campbell Collaboration (https://www.campbellcollaboration.org). The meta-analysis component was further modified appropriately for the synthesis of sensitivity and specificity results. RESULTS: A total of 1,055 cervical cancer cases who had received pelvic radiation with or without chemotherapy from ten cohort studies were evaluated. The overall pooled sensitivity and specificity of HPV DNA testing was 0.84 (95% confidence interval [CI]= 0.66-0.94) and 0.35 (95% CI=0.20-0.54) respectively. The positive likelihood ratio was 1.3 (95% CI=1.0-1.7) and the negative likelihood ratio was 0.45 (95% CI=0.18-1.10) with an estimated diagnostic odds ratio of 3 (95% CI=1-9). CONCLUSION: The screening for HPV DNA testing during follow-up facilitates early detection of recurrence after radiotherapy.

The Utility of Urine-Based Sampling for Cervical Cancer Screening in Low-Resource Settings.

Background: WHO has recommended Visual Inspection with Acetic acid (VIA) or Human Papillomavirus (HPV) DNA testing if feasible, for cervical cancer screening in low income countries. However, the number of women undergoing screening is very low as a result of limited information, inadequate infrastructure and invasive nature of sampling. Methods: A cross sectional study was carried out comparing HPV DNA detection by Polymerase Chain Reaction (PCR) in paired cervical and urine samples procured from histologically confirmed cervical cancer cases. Results: Amongst the samples collected from 114 cervical cancer cases, HPV DNA was tested positive in cervical samples of 89 (78.1%) and urine samples of 55 (48.2%) patients. The agreement between the two sampling methods was 66.7% and the kappa value was 0.35 indicating a fair agreement. The sensitivity of HPV detection using urine samples was 59.6% (95% confidence interval 49.16%-69.15%) and the specificity was 92% (95% confidence interval 75.0%-97.8%). Conclusion: Even though not acceptable as an HPV DNA screening tool due to low sensitivity, the urine sampling method is inexpensive and more socially acceptable for large epidemiological surveys in developing countries to estimate the burden.

Histomorphometric effects of gemcitabine on Swiss albino mice spermatogenesis.

BACKGROUND: Spermatogenesis is a highly conserved and regulated process and it is sensitive to fluctuations in the physical and chemical environment. Gemcitabine is a novel antimetabolic anticancer drug used frequently in the treatment of many cancers. This study aimed to investigate the histomorphometric effects of gemcitabine on spermatogenesis in Swiss albino mice. MATERIALS AND METHODS: Gemcitabine in high and low doses (80 and 40 mg/kg) injected intraperitoneally to inbred Swiss albino mice. Gross testicular features and seminiferous tubular histomorphometry was studies at the end of 7(th), 14(th) day and at 2 months sperm shape abnormalities were studied. RESULTS: Seminiferous tubular morphology was altered significantly, showing a reduction in height, perimeter and area in a dose dependent manner. Sertoli cell number decreased. Basement membrane thickness was reduced and it appeared to be permanent, with statistically insignificant changes even after 2 months. There was a reduction of intertubular spaces. Sperms have shown banana heading, decapitation and loss of normal hook of head. The effects were partially reversible at the end of 2 months. CONCLUSION: It was concluded that gemcitabine affects the process of spermatogenesis adversely in a dose and time dependent manner and the effects are partially reversible.

Neuroendocrine carcinoma of the cervix presenting as intractable hyponatremic seizures due to paraneoplastic SIADH-a rare case report and brief review of the literature.

Herein is presented an interesting case of small-cell neuroendocrine carcinoma of the cervix which initially manifests as seizures due to hyponatremia caused by paraneoplastic syndrome of inappropriate anti diuretic hormone (SIADH). Awareness of a paraneoplastic syndrome at presentation can lead to early diagnosis and early initiation of treatment. The management is also unique in that it combines treating the paraneoplastic aspects as well as targeting the tumour itself. Multimodality treatment gives the best outcome in this aggressive tumour.

Evolution of surgery in advanced epithelial ovarian cancer in a dedicated gynaecologic oncology unit-seven year audit from a tertiary care centre in a developing country.

AIMS: To audit our performance as a dedicated gynaecologic oncology unit and to analyse how it has evolved over the years.To retrospectively evaluate the outcome of advanced ovarian cancer treated with neoadjuvant chemotherapy (NACT) followed by interval surgery versus upfront surgery. METHODS AND RESULTS: One hundred and ninety-eight patients with advanced epithelial ovarian cancer (EOC) who were treated from 2004 to 2010 were analysed. Eighty-two patients (41.4%) underwent primary surgery and 116 (58.6%) received NACT. Overall, an optimal debulking rate of 81% was achieved with 70% for primary surgery and 88% following NACT. The optimal cytoreduction rate has improved from 55% in 2004 to 97% in 2010. In primary surgery, the optimal debulking rate increased from 42.8% in 2004 to 93% in 2010, whereas in NACT group the optimal cytoreduction rate increased from 60% to 100% by 2010. On the basis of the surgical complexity scoring system it was found that surgeries with intermediate complexity score had progressively increased over the years. There was a mean follow-up of 21 months ranging from 6 to 70 months. The progression-free survival and overall survival (OS) in patients undergoing primary surgery were 23 and 40 months, respectively, while it was 22 and 40 months in patients who received NACT. However, patients who had suboptimal debulking, irrespective of primary treatment, had significantly worse OS (26 versus 47 months) compared with those who had optimal debulking. CONCLUSIONS: As a dedicated gynaecologic oncology unit there has been an increase in the optimal cytoreduction rates. The number of complex surgeries, as denoted by the category of intermediate complexity score, has increased. Patients with advanced EOC treated with NACT followed by interval debulking have comparable survival to the patients undergoing primary surgery. Optimal cytoreduction irrespective of primary modality of treatment gives better survival.

Unique surgical issues in the management of a giant retroperitoneal schwannoma and brief review of literature.

Ancient Schwannoma, though benign, can cause diagnostic dilemma because of its clinical presentation and imaging features. We report the management of a giant retroperitoneal schwannoma in a 19-year-old young lady who presented with lower abdominal distension. CT scan reported a large heterogenous lesion in the abdominopelvic retroperitoneum (42 cm × 16 cm × 16 cm) as a malignant tumor. The unique problems we encountered were the enormous size, the location of major part of the tumor in the pelvis, the need for fertility preservation, the external iliac vessels stretching over the tumor making mobilization surgically demanding, and the prospects of neurological deficits. An en bloc resection of schwannoma with common iliac, external iliac and internal iliac veins, internal iliac artery, femoral and obturator nerves, and iliopsoas muscle was done maintaining oncological principles. External iliac artery that was cut to facilitate tumor mobilization was reanastomosed at the end of the procedure. Postoperatively patient had uneventful recovery with patchy sensory loss, foot drop, and quadriceps weakness which was rehabilitated with a foot drop splint and active physiotherapy.

Krukenberg tumour as the initial presentation of Peutz-Jeghers syndrome.

Peutz-Jeghers syndrome (PJS) is an hereditary syndrome characterized by gastrointestinal polyposis and mucocutaneous pigmentation. PJS patients are at increased risk of developing various cancers, especially of the gastrointestinal and gynaecological tracts. Colonic adenocarcinoma is one of the more common tumours that occur in PJS. We report a young lady presenting with a large ovarian tumour, later diagnosed to have PJS with colonic signet cell adenocarcinoma and synchronous ovarian metastasis.

The significance of the site of origin in primary peritoneal carcinosarcoma: case report and literature review.

Primary peritoneal carcinomas are rare, highly aggressive malignant neoplasms containing both sarcomatous and carcinomatous elements. Surgical debulking is the mainstay of treatment for primary peritoneal carcinomas. Systemic chemotherapy is advised in all cases because of the early spreading of these tumours. We report on a case of primary peritoneal carcinosarcoma occurring in a 22-year-old woman.

Carcinosarcoma of the uterus-a single institution retrospective analysis of the management and outcome and a brief review of literature.

Uterine carcinosarcomas are highly aggressive tumors of the uterus associated with a poor prognosis. Though initially classified as sarcomas, now these tumors are classified as carcinomas. The management approach of carcinosarcomas has also changed from those used for high grade sarcomas to that used for managing high grade endometrial carcinomas. The purpose of our study was to analyze the management and outcome of patients with uterine carcinosarcomas treated at our institution and also to attempt a brief review regarding the management of uterine carcinosarcomas. We did a retrospective analysis of all patients with a diagnosis of carcinosarcoma of the uterus treated at our Institution from January 2005 till December 2010. All Patients with a pathological diagnosis of carcinosacrcoma or malignant mixed mullerian tumours of the uterus were included. Data was obtained from the hospital electronic medical records and the hospital cancer registry. Data was analyzed using SPSS v.17. During this 6 year period we had 20 patients with carcinosarcoma of the uterus. 75 % of the patients belonged to Stage I and II. 95 % of the patients underwent Hysterectomy with Bilateral salpingo oophorectomy and 60 % had lymphadenectomy also along with hysterectomy.8 patients had disease recurrence . In patients who had gross extrauterine disease at the time of surgery , the survival was only 9 months whereas in patients who had complete staging with disease confined to the uterus , the survival was 36 months. Carcinosarcomas, accounts for more than 15 % of the uterine cancer associated deaths. Surgery remains the cornerstone of management for these tumors and surgery with pelvic and para aortic lymphadenectomy and peritoneal and omental biopsies is required for the correct staging of the disease and may also provide a survival advantage. Radiation therapy has been shown to provide only better local control without any survival advantage. Further studies are needed to assess whether chemotherapy offers a definite survival benefit in uterine carcinosarcomas.

Disseminated peritoneal leiomyosarcomas after laparoscopic "myomectomy" and morcellation.

Herein is reported a case of disseminated peritoneal leiomyosarcoma arising shortly after laparoscopic myomectomy and specimen retrieval with an electromechanical morcellator. The topography of the sarcomas suggests morcellation as a contributing factor. This case shows that caution should be exercised when selecting patients for laparoscopic myomectomy and stresses the need for a thorough pathologic examination of the specimen retrieved.