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.

Brain MRI segmentation of Zika-Exposed normocephalic infants shows smaller amygdala volumes.

BACKGROUND: Infants with congenital Zika syndrome (CZS) are known to exhibit characteristic brain abnormalities. However, the brain anatomy of Zika virus (ZIKV)-exposed infants, born to ZIKV-positive pregnant mothers, who have normal-appearing head characteristics at birth, has not been evaluated in detail. The aim of this prospective study is, therefore, to compare the cortical and subcortical brain structural volume measures of ZIKV-exposed normocephalic infants to age-matched healthy controls. METHODS AND FINDINGS: We acquired T2-MRI of the whole brain of 18 ZIKV-exposed infants and 8 normal controls on a 3T MRI scanner. The MR images were auto-segmented into eight tissue types and anatomical regions including the white matter, cortical grey matter, deep nuclear grey matter, corticospinal fluid, amygdala, hippocampus, cerebellum, and brainstem. We determined the volumes of these regions and calculated the total intracranial volume (TICV) and head circumference (HC). We compared these measurements between the two groups, controlling for infant age at scan, by first comparing results for all subjects in each group and secondly performing a subgroup analysis for subjects below 8 weeks of postnatal age at scan. ZIKV-exposed infants demonstrated a significant decrease in amygdala volume compared to the control group in both the group and subgroup comparisons (p<0.05, corrected for multiple comparisons using FDR). No significant volume differences were observed in TICV, HC, or any specific brain tissue structures or regions. Study limitations include small sample size, which was due to abrupt cessation of extramural funding as the ZIKV epidemic waned. CONCLUSION: ZIKV-exposed infants exhibited smaller volumes in the amygdala, a brain region primarily involved in emotional and behavioral processing. This brain MRI finding may lead to poorer behavioral outcomes and warrants long-term monitoring of pediatric cases of infants with gestational exposure to Zika virus as well as other neurotropic viruses.

Successful Treatment of Balamuthia mandrillaris Granulomatous Amebic Encephalitis with Nitroxoline.

A patient in California, USA, with rare and usually fatal Balamuthia mandrillaris granulomatous amebic encephalitis survived after receiving treatment with a regimen that included the repurposed drug nitroxoline. Nitroxoline, which is a quinolone typically used to treat urinary tract infections, was identified in a screen for drugs with amebicidal activity against Balamuthia.

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.

Superficial fibromatosis: MRI radiomics and T2 mapping correlate with treatment response.

BACKGROUND: Superficial fibromatosis exhibits variable MR signal intensity due to collagenous and fibroproliferative components. Quantifying this signal heterogeneity using image texture analysis and T2-mapping could have prognostic and therapeutic implications. METHODS: This IRB-approved retrospective study included 13 patients with superficial fibromatosis, managed by observation, electron beam radiotherapy (EBT), or pentoxifylline/vitamin E. Two-dimensional regions of interest (ROIs) were drawn on proton-density or T2-weighted MRI for radiomics feature analysis, and corresponding T2-maps. Comparisons were made between baseline and follow-up T2 relaxation times and radiomics features: Shannon's entropy, kurtosis, skewness, mean of positive pixels (MPP), and uniformity of distribution of positive gray-level pixel values (UPP). RESULTS: There were 19 nodules in 13 subjects. Mean patient age was 60 years; 62% (8/13) were female; mean follow-up was 9.7 months. Nodule diameter at baseline averaged 18.2 mm (std dev 16.2 mm) and decreased almost 10% to 16.6 mm (p = 0.1, paired t-test). Normalized T2 signal intensity decreased 23% from 0.71 to 0.55 (p = 0.03, paired t-test). T2 relaxation time decreased 16% from 46.5 to 39.1 ms (p < 0.001, paired t-test). Among radiomics features, skewness increased to 0.71 from 0.41 (p = 0.03, paired t-test), and entropy decreased from 8.37 to 8.03 (p = 0.05, paired t-test); differences in other radiomics features were not significant. CONCLUSIONS: Radiomics analysis and T2-mapping of superficial fibromatosis is feasible; robust decreases in absolute T2 relaxation time, and changes in image textural features (increased skewness and decreased entropy) offer novel imaging biomarkers of nodule collagenization and maturation.

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.

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.

Correlation of Pattern of Spread and Outcomes in Advanced Epithelial Ovarian Cancers.

The purpose of this study was to correlate the pattern of spread with oncological outcomes in advanced ovarian cancer patients. This is a retrospective analysis of 55 consecutive patients who had advanced epithelial ovarian cancer or primary peritoneal carcinomatosis (stages 3C and 4) with primary surgical intervention as the initial modality of treatment. Based on the spread of disease, they were further classified into class A: disease confined to the pelvis (excluded); class B: disease extending to the lower abdomen and omentum; class C: diffuse small-bowel disease with or without A, B, or D; and class D: disease in the upper abdomen. There were 17 patients (30.9%) in class B, 17 (30.9%) in class C, and 21 (38.2%) in class D. The number of patients with suboptimal cytoreduction was highest in class C (six patients). At the end of follow-up (median 38.6 months), 16 patients had no evidence of disease and 26 patients were alive with disease. The 3-year overall survival rates in classes B, C, and D were 94.1, 52.5, and 93.3%, respectively. The 3-year progression-free survival rates were 55.8, 11.8, and 41.9%, respectively. The rates were lowest for class C. The differences in the overall survival rate (p < 0.001) and progression-free survival rate (p = 0.001) were statistically significant. In advanced ovarian cancer patients, the presence of disease in the small-bowel serosa and mesentery results in poorer outcomes in terms of overall and progression-free survival. The number of patients with suboptimal cytoreduction was also highest in this group.

Apparent diffusion coefficient map of a case of extramedullary plasmacytoma.

Plasmacytomas are rare tumors, which arise from the monoclonal proliferation of malignant plasma cells. They may affect either the bony skeleton or rarely the soft tissues, the latter being referred to as extramedullary or extraosseous. We report a case of an extramedullary plasmacytoma that presented as a soft tissue mass involving the muscles of the left leg, in a patient who was previously treated for multiple myeloma. We describe the MR Imaging characteristics of the tumor and highlight the usefulness of diffusion-weighted imaging with apparent diffusion coefficient mapping.