The tumor microenvironment (TME) plays a major role in the pathogenesis of multiple cancer types, including upper-gastrointestinal (GI) cancers that currently lack effective therapeutic options. Cancer-associated fibroblasts (CAF) are an essential component of the TME, contributing to tumorigenesis by secreting growth factors, modifying the extracellular matrix, supporting angiogenesis, and suppressing antitumor immune responses. Through an unbiased approach, we have established that IL-6 mediates cross-talk between tumor cells and CAF not only by supporting tumor cell growth, but also by promoting fibroblast activation. As a result, IL-6 receptor (IL6Rα) and downstream effectors offer opportunities for targeted therapy in upper-GI cancers. IL-6 loss suppressed tumorigenesis in physiologically relevant three-dimensional (3D) organotypic and 3D tumoroid models and murine models of esophageal cancer. Tocilizumab, an anti-IL6Rα antibody, suppressed tumor growth in part via inhibition of STAT3 and MEK/ERK signaling. Analysis of a pan-cancer TCGA dataset revealed an inverse correlation between IL-6 and IL6Rα overexpression and patient survival. Therefore, we expanded evaluation of tocilizumab to head and neck squamous cell carcinoma patient-derived xenografts and gastric adenocarcinoma xenografts, demonstrating suppression of tumor growth and altered STAT3 and ERK1/2 gene signatures. We used small-molecule inhibitors of STAT3 and MEK1/2 signaling to suppress tumorigenesis in the 3D organotypic model of esophageal cancer. We demonstrate that IL6 is a major contributor to the dynamic cross-talk between tumor cells and CAF in the TME. Our findings provide a translational rationale for inhibition of IL6Rα and downstream signaling pathways as a novel targeted therapy in oral-upper-GI cancers. These findings demonstrate the interaction of esophageal cancer and cancer-associated fibroblasts through IL-6 signaling, providing rationale for a novel therapeutic approach to target these cancers. .

Aim To evaluate the association between changes in platelet indices (platelet count, mean platelet volume, platelet distribution width) and development of preeclampsia. Materials and methods Two hundred pregnant women at 20 to 24 weeks of gestation with singleton pregnancy and normal blood pressure were enrolled after taking well-informed consent. At monthly intervals CBC (complete blood count) was done from 20 to 24 weeks till 40 weeks and 7 days after delivery. Data regarding changes in platelet indices with increasing gestation was collected and analyzed. Results Platelet count decreased significantly in patients with preeclampsia compared to normal pregnant patients (19.4% vs 7.4%). Mean platelet volume increased significantly in preeclampsia patients (44.5% vs 9.22%). Increase in PDW was observed significantly in patients with preeclampsia (47.19% vs 29.4%). Conclusion Patients with preeclampsia are more likely to have significant decrease in platelet count, increase in PDW and MPV. These changes can be observed at an earlier gestational age than significant rise in BP can be observed and are directly proportional to progressive rise in hypertension. Thus, estimation of platelet indices can be considered as an early, simple and cost-effective procedure in the assessment of severity of preeclampsia. How to cite this article Dadhich S, Agrawal S, Soni M, Choudhary R, Jain R, Sharma S, Saini SL. Predictive Value of Platelet Indices in Development of Preeclampsia. J South Asian Feder Obst Gynae 2012;4(1):17-21.

OBJECTIVES Post-lobectomy bleeding is uncommon and rarely studied. In this study, we aimed to determine the incidence of post-lobectomy haemorrhage and compare the outcomes of reoperation and non-operative management. METHODS We conducted a single-institution review of lobectomy cases from 2009 to 2018. The patients were divided into two groups based on the treatment for postoperative bleeding: reoperation or transfusion of packed red blood cells with observation. Transfusion correcting intraoperative blood loss was excluded. One or more criteria defined postoperative bleeding: (i) drop in haematocrit ≥10 or (ii) frank, sustained chest tube bleeding with or without associated hypotension. Covariates included demographics, comorbidities and operative characteristics. Outcomes were operative mortality, complications, length of hospital stay and readmission within 30 days. RESULTS Following 1960 lobectomies (92% malignant disease, 8% non-malignant), haemorrhage occurred in 42 cases (2.1%), leading to reoperation in 27 (1.4%), and non-operative management in 15 (0.8%). The median time to reoperation was 17 h. No source of bleeding was identified in 44% of re-explorations. Patients with postoperative haemorrhage were more often male (64.3% vs 41.2%; P < 0.01) and more likely to have preoperative anaemia (45.2% vs 26.5%; P = 0.01), prior median sternotomy (14.3% vs 6.0%; P = 0.04), an infectious indication (7.1% vs 1.8%; P = 0.01) and operative adhesiolysis (45.2% vs 25.8%; P = 0.01). Compared with non-operative management, reoperation was associated with fewer units of packed red blood cells transfusion (0.4 vs 1.9; P < 0.001), while complication rates were similar and 30-day mortality was absent in either group. CONCLUSIONS Haemorrhage after lobectomy is associated with multiple risk factors. Reoperation may avoid transfusion. A prospective study should optimize timing and selection of operative and non-operative management.

Objective: To analyze the cases of maternal mortality over a period of 3 years with regard to direct, indirect and associated causes and social correlates. Materials and methods:Retrospective evaluation of the cases with respect to causes, admission to mortality interval, age, parity, antenatal booking, socioeconomic status, etc. and systemic analysis of all contributing factors. Result and observation:A total of 66.67% of the deaths were due to direct causes with obstetric hemorrhage being the most common cause followed by puerperal sepsis. Anemia was the most important indirect cause followed by hepatitis and cardiovascular diseases. Conclusion:A large number of maternal deaths seem to be avoidable if we are able to strengthen our maternity and child health services. Equally important, however, remains the upgradation of the status of females in the society with emphasis on literacy and general health awareness.