Immunomodulatory Drugs for the Treatment of B Cell Malignancies.

Accumulating evidence suggests that the tumor microenvironment (TME) is involved in disease progression and drug resistance in B cell malignancies, by supporting tumor growth and facilitating the ability of malignant cells to avoid immune recognition. Immunomodulatory drugs (IMiDs) such as lenalidomide have some direct anti-tumor activity, but critically also target various cellular compartments of the TME including T cells, NK cells, and stromal cells, which interfere with pro-tumor signaling while activating anti-tumor immune responses. Lenalidomide has delivered favorable clinical outcomes as a single-agent, and in combination therapy leads to durable responses in chronic lymphocytic leukemia (CLL) and several non-Hodgkin lymphomas (NHLs) including follicular lymphoma (FL), diffuse large B cell lymphoma (DLBCL), and mantle cell lymphoma (MCL). Recently, avadomide, a next generation cereblon E3 ligase modulator (CELMoD), has shown potent anti-tumor and TME immunomodulatory effects, as well as promising clinical efficacy in DLBCL. This review describes how the pleiotropic effects of IMiDs and CELMoDs could make them excellent candidates for combination therapy in the immuno-oncology era-a concept supported by preclinical data, as well as the recent approval of lenalidomide in combination with rituximab for the treatment of relapsed/refractory (R/R) FL.

Desmoid Fibromatosis of Maxillary Sinus Masquerading as Nasal Polyp: A Case Report.

Desmoid fibromatosis is also known as aggressive fibromatosis. It is a neoplastic monoclonal proliferation of fibroblasts, with an incidence of 2 to 4 per million per year. Its incidence peaks at 8 years of age and in the third/fourth decades of life. Here we discussed a patient in third decade of life who presented with unilateral nasal blockage with a picture suggestive of sinonasal polyposis on examination. On histopathology, he was diagnosed with Desmoid fibromatosis. Though a rare entity, Desmoid fibromatosis should be kept in mind as a differential diagnosis for appropriate patient management. As per our knowledge, in India this is the first documented case of desmoid fibromatosis arising from maxillary sinus.

Clinicopathological Significance of Tumor Budding in Breast Carcinoma.

BACKGROUND: Tumour budding Tuberculosis is a new prognostic marker whose role in breast cancer is still under evaluation. Our aim was to study Tuberculosis in breast carcinoma and correlate it with other prognostic markers. METHODS: A descriptive cross-sectional study was conducted over 2 years on 75 invasive breast carcinoma specimens and biopsies. Hematoxylin and Eosin sections were examined for tumour grade, stage, molecular subtype, necrosis, lymphovascular invasion inflammation and counting of Tuberculosis. Lymph node metastasis was studied only in mastectomies. TB was defined as a cluster of 1-5 tumour cells and counted in 10 consecutive 400X fields. The cut-off for high grade TB was taken as ?10 per 10 HPFs. Immunohistochemical staining was done for molecular subtyping and differentiating Tuberculosis from mimickers. Statistical analysis was done using chi square test and Fischer's exact test. RESULTS: Tuberculosis was present in 66/75 cases; 53% (n=35) were high grade. Among these, majority were of T2 (74%, n= 26), grade 2 (52%, n= 18), luminal A (34%, n= 12), had 3+ inflammation (46%, n= 16) and peripheral tumour buds (54%). Necrosis and lymphovascular invasion were absent in 77% and 71%, respectively. Lymph node metastasis was seen in 63% (n= 25/28) cases. Statistically significant association (p= 0.016) was observed between degree of inflammation and Tuberculosis grade. However, no significant association was observed between TB and other prognostic markers of breast carcinoma. CONCLUSIONS: In our study, association of Tuberculosis with different prognostic markers was appreciated but was not statistically significant. However, it highlights need for standardization of Tuberculosis reporting.

A meta-analysis on the prevalence of Taenia solium and Taenia saginata infections in India.

Tapeworm infections in humans are considered to be a significant public health menace. Despite its public health importance, the data on tapeworm infection remains fragmented and underutilised. The present study reviews the overall burden and distribution of taeniasis and cysticercosis caused by Taenia solium and Taenia saginata in India by conducting a systematic review of the scientific literature based on Preferred Reporting Items for Systematic reviews and Meta-Analyses guidelines. Data from 19 eligible articles were analysed and the prevalence of T. solium-associated taeniasis/cysticercosis was found to be 11.06% (95% confidence interval [CI] 6.856 to 16.119) and the prevalence of T. saginata-associated taeniasis was found to be 4.7% (95% CI 3.301 to 6.301). This systematic review and meta-analysis provides a comprehensive analysis of the available literature on tapeworm infections and assesses the burden of Taenia infection from India, identifying areas of high prevalence requiring active surveillance and public health interventions.

Tumor budding in breast carcinoma: A systematic review and meta-analysis.

ABSTRACT: Tumor budding is gaining importance as a prognostic factor in various carcinomas due to its association with epithelial-mesenchymal transition (EMT) and hence clinical outcome. Reporting tumor budding in breast cancer lacks homogeneity. We aim to systematically review the existing literature and conduct a meta-analysis to assess the prognostic implication of tumor budding in breast carcinoma. A systematic search was performed to identify studies that compared different prognostic variables between high- and low-grade tumor budding. Quality assessment was performed using a modified Newcastle Ottawa Scale. Dichotomous variables were pooled using the odds ratio using the Der-Simonian-Laird method. Meta-analysis was conducted to study the association between low/high-grade tumor budding and tumor grade, lymph node metastasis, lymphovascular invasion, ER, PR, HER2neu, KI67, and the molecular subtype triple-negative breast carcinoma. Thirteen studies with a total of 1763 patients were included. A moderate risk of bias was noted. The median bias scoring was 7 (6-9). High-grade tumor budding was significantly associated with lymph node metastasis (OR: 2.25, 95% CI: 1.52-3.34, P < 0.01) and lymphovascular invasion (OR: 3.14, 95% CI: 2.10-4.71, P < 0.01), and low-grade budding was significantly associated with triple-negative breast carcinoma (OR: 0.61, 95% CI: 0.39-0.95, P = 0.03)There was significant heterogeneity in the assessment and grading of tumor budding; thus, a checklist of items was identified that lacked standardization. Our meta-analysis concluded that tumor budding can act as an independent prognostic marker for breast cancer.

Prevalence of Pregnancy Associated Malaria in India.

Malaria in pregnancy is a major public health concern. It results in impaired maternal health and adversely effects fetal and perinatal outcomes. The present systematic review was conducted to assess the prevalence, distribution and adverse pregnancy outcomes in malaria infected females in India. A comprehensive search and review of PubMed and Web of Science based on PRISMA guidelines was carried out to find articles reporting prevalence of malaria in pregnant women from India. Data from 16 studies were analyzed and prevalence of malaria among pregnant women in India was found to be 11.4 % (95 % CI: 7.3, 16.3). Prevalence of malaria among asymptomatic and symptomatic pregnant women was found to be 10.62% (95% CI: 6.05, 16.23) and 13.13% (95% CI: 7.2, 20.52), respectively. P. falciparum and P. vivax were both reported with in the same population. The geospatial distribution of malaria in pregnancy spanned over nine very populous states of India. The review also reported severe maternal and perinatal outcomes. Given the seriousness of malaria in pregnant women and its effects on the fetus and new-born, a stringent district wise guideline for early detection and prophylaxis in regions identified in this review will help in its better control.

Prevalence of Amoebiasis and Associated Complications in India: A Systematic Review.

PURPOSE: Intestinal protozoan parasites are responsible for diarrheal diseases causing significant morbidity and mortality. Entamoeba histolytica is the principle protozoan parasite associated with diarrheal infections. The infection is often associated with inaccessibility to clean drinking water and poor sanitary conditions in low- and middle-income countries including India. A comprehensive systematic review was performed to evaluate a reliable nationwide estimate for prevalence and geographic distribution of amoebiasis in India and the complications associated with it. METHODS: We used the PRISMA guidelines to perform a systematic review and meta-analysis of articles published between the year 2001-2020. Two English language databases PubMed and Web of Science were searched to achieve relevant studies. RESULTS: Initial searches resulted in 467 studies out of which 64 eligible articles involving data from 289,659 human subjects from 12 states and 4 union territories were included in the final analysis. Prevalence of amoebiasis ranged from 3-23% in asymptomatic population, 0.64-11% in symptomatic patients and 1-17.5% in HIV-infected patients. Highest prevalence was seen in Tamil Nadu, Andaman Nicobar Island and North East India. Extra intestinal invasion of Entamoeba histolytica leading to complications such as amoebic liver abscess, amoebic colitis, colonic perforation and ameboma were also reported. Such complications have the potential to increase healthcare burden and may prove to be fatal. CONCLUSION: Amoebiasis remains a significant public health issue in India responsible for diarrheal diseases causing significant morbidity and mortality. Entamoeba histolytica is the principle protozoan parasite associated with amoebiasis. Public health efforts should be directed towards its control and better diagnostic methods should be employed for distinguishing between pathogenic and non-pathogenic species of Entamoeba.