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Background Colorectal cancer (CRC) remains a significant global health burden, ranked among the most common causes of cancer-related fatalities. While insulin resistance (IR) biomarkers have been associated with CRC prognosis, their role in predicting metastasis remains unclear. Metastasis remains a critical determinant of prognosis and treatment planning in CRC. Identifying precise biomarkers can improve CRC management. This study evaluates the prognostic efficacy of lipid-based IR biomarkers in predicting metastasis in treatment-naïve CRC patients and selects the most appropriate one. We also explore their association with clinicopathological characteristics. Method Eighty-seven CRC patients (metastatic, n  = 24; non-metastatic, n  = 63) from four tertiary hospitals in India were analysed. Clinical data included TNM staging, ECOG-PS, KPS, CEA, and lipid profiles. Statistical tests included Fisher’s exact test, Mann-Whitney U-test, ROC curve analysis, Spearman’s correlation, multiple linear regression, and binary logistic regression. Results Statistically significant differences were observed in job status, diet, smoking, alcohol use, diabetes, BMI, and IR markers between metastatic and non-metastatic CRC patients. Among the IR biomarkers, the ratio of LDL to HDL (LHR) demonstrated the highest diagnostic accuracy with an AUC of 0.867 ( p  < 0.05, CI: 0.79–0.94), a sensitivity of 83.3%, and a specificity of 74.6%. Spearman correlation analysis unveiled a moderate-positive relationship between IR biomarkers and carcinoembryonic antigen (CEA) levels, except for the triglyceride glucose index (TyG). Binary logistic regression identified LHR as the sole significant predictor of metastasis, with a one-unit increase in LHR corresponding to a 19.35% higher likelihood of metastasis. Multiple linear regression confirmed a moderate, significant combined effect of TNM staging, ECOG-PS, KPS, and LHR. Conclusion LHR strongly predicts metastasis in CRC patients, with high sensitivity and specificity among IR biomarkers. Its significant association with TNM staging, ECOG-PS, and CEA levels highlights its potential for early detection of metastasis and improved risk stratification. Larger studies are needed to validate its clinical utility for personalised treatment planning.

Abstract Background: Carcinoma gallbladder is mostly diagnosed in locally advanced, inoperable, or metastatic stage. Best supportive care with or without palliative chemotherapy is the only feasible treatment option. Gemcitabine and platinum agents' combination is the most effective first option with no well-established second-line regimen. Objectives: We planned to study the response rate, safety, the progression-free survival (PFS), and overall survival (OS) on the second-line FOLFOX-4 chemotherapy. Methods: This is a prospective single-arm observational study of 29 eligible patients. Patients were studies for response to the second-line FOLFOX-4 chemotherapy. Positron emission tomography/computed tomography scans were done for response assessment; chemotherapy toxicity was graded using National Cancer Institute clinical toxicity criteria; and survival rates (PFS and OS) were studied. Results: Among the 39 patients with gemcitabine-based chemotherapy (CT-1), the median PFS-1 was 6.5 months. Twenty-nine patients received second-line chemotherapy (CT-2). Responses observed complete response in 2/29, partial response in 7/29, stable disease in 1/29 patients, and progressive disease in 19/29. The overall response rate was 9/29 (31.0%). Grades 2–4 toxicities were anemia (17.95%), thrombocytopenia (12.82%), neutropenia (12.82%), and peripheral neuropathy (7.69%). The median OS was 9.13 months. Late PFS-1 (>median PFS-1) patients had significantly lower mortality as compared to early PFS-1, odds ratio of 0.251 ( P = 0.002), and median PFS-2 was 2.53 months. Conclusion: After the failure of gemcitabine and platinum-based chemotherapy, FOLFOX-4 is modestly effective, fairly well tolerated and this needs to be proven in a larger randomized phase 3 study. Further research into the pathogenesis of biliary tract cancer with the aim to identify new targets for treatments is required.

Abstract Background and Objectives: L-asparaginase has become the backbone of acute lymphoblastic leukemia induction. In Berlin–Frankfurt–Munster (BFM) 95/2000 protocols, L-asparaginase was given twice weekly for initial 4 weeks. While sufficient L-asparaginase levels are important, there is no apparent correlation between high L-asparaginase levels and minimal residual disease (MRD). In view of toxicities of L-asparaginase, we planned to study the effect of dose and schedule of Escherichia coli -derived L-asparaginase on early MRD by phasing the same total dose, once a week over 8 weeks. Methods: This prospective, observational study enrolled 45 children and young adults ≤40 years. Modified BFM 95 protocol was followed. Weekly 5000 IU/m 2 L-asparaginase was given intravenously, and MRD was analyzed at the end of 4 weeks (MRD1) and at 8 weeks (MRD2), using multicolor flow cytometry. MRD positive was defined as residual blasts ≥0.01%. Results: Thirty-one patients were eligible for final analysis. Nine could receive scheduled eight doses of L-asparaginase and 22 patients received less than eight doses. We analyzed age, gender, diagnosis, prednisone response, cytogenetics, central nervous system status, BFM risk group, MRD2, and relapse. L-asparaginase dose association was not statistically significant with respect to MRD2 ( P = 0.237). There were no cases of pancreatitis, hypersensitivity, bleeding, or thrombosis. Reasons for patients receiving less than the scheduled eight doses were low serum fibrinogen levels and liver dysfunction. This study revealed 8 MRD1-negative and 13 MRD2-negative patients. Conclusion: L-asparaginase dose intensity does not affect early MRD. Phasing L-asparaginase over 8 weeks could lead to the achievement of more MRD2-negative status and thereby improve long-term outcome. This strategy may also reduce the incidence of adverse drug events.