Cholangiocarcinomas (CCA) pose a complex challenge in oncology due to diverse etiologies, necessitating tailored therapeutic approaches. This review discusses the risk factors, molecular pathology, and current therapeutic options for CCA and explores the emerging strategies encompassing targeted therapies, immunotherapy, novel compounds from natural sources, and modulation of gut microbiota. CCA are driven by an intricate landscape of genetic mutations, epigenetic dysregulation, and post-transcriptional modification, which differs based on geography (e.g., for liver fluke versus non-liver fluke-driven CCA) and exposure to environmental carcinogens (e.g., exposure to aristolochic acid). Liquid biopsy, including circulating cell-free DNA, is a potential diagnostic tool for CCA, which warrants further investigations. Currently, surgical resection is the primary curative treatment for CCA despite the technical challenges. Adjuvant chemotherapy, including cisplatin and gemcitabine, is standard for advanced, unresectable, or recurrent CCA. Second-line therapy options, such as FOLFOX (oxaliplatin and 5-FU), and the significance of radiation therapy in adjuvant, neoadjuvant, and palliative settings are also discussed. This review underscores the need for personalized therapies and demonstrates the shift towards precision medicine in CCA treatment. The development of targeted therapies, including FDA-approved drugs inhibiting FGFR2 gene fusions and IDH1 mutations, is of major research focus. Investigations into immune checkpoint inhibitors have also revealed potential clinical benefits, although improvements in survival remain elusive, especially across patient demographics. Novel compounds from natural sources exhibit anti-CCA activity, while microbiota dysbiosis emerges as a potential contributor to CCA progression, necessitating further exploration of their direct impact and mechanisms through in-depth research and clinical studies. In the future, extensive translational research efforts are imperative to bridge existing gaps and optimize therapeutic strategies to improve therapeutic outcomes for this complex malignancy.

Advanced bladder cancer patients have historically failed to achieve prolonged duration of response to conventional chemotherapy and needed better first-line treatment regimens. The approval of nivolumab in combination with gemcitabine and cisplatin and pembrolizumab with antibody–drug conjugate enfortumab vedotin has revolutionized the first-line treatment of advanced bladder cancer in many countries. In this review, we summarize the intricate differences between the two landmark clinical trials that led to their incorporation into the current standard of care for advanced bladder cancer. We further discuss newer novel treatment options in the second and subsequent lines of treatment on progression, like immunotherapy in combination with other agents, including fibroblast growth factors receptor inhibitors, human epidermal growth factor inhibitors, antibody–drug conjugates, tyrosine kinase inhibitors, and novel antibodies. Finally, we discuss the integration of these novel therapies into current clinical practice amidst the rapidly evolving landscape of advanced bladder cancer treatment, aiming to enhance patient outcomes.

This may be extended to a few months. Our institutional protocol has been to offer intrathecal chemotherapy (ITC) to patients having solid tumors with cerebrospinal fluid (CSF) cytology positive leptomeningeal carcinomatosis. This study was performed to describe the oncological outcomes in this cohort and their determinants. Methods: A retrospective review of data of patients treated at Amrita Institute of Medical Sciences, Kochi, India was performed. Patients with CSF cytology positive solid tumors treated with triple ITC (methotrexate, cytosine arabinoside and hydrocortisone) were assessed for patient characteristics, treatment response, survival and the factors affecting them. Results: Twenty patients of LC treated with triple ITC were included in the study. The median age of the study group was 49 years with a slight female preponderance (55%). All patients had positive CSF cytology with mean CSF glucose of 60 mg/dL, mean CSF protein of 92 mg/dL and mean cell count of 5. Breast cancer was the most common primary tumor (45%), followed by lung (35%) and stomach (5%). Symptomatic improvement was reported in 70% of patients after initiating ITC. Median overall survival (OS) at 6 and 12 months was 38% and 14%, respectively. Median progression-free survival (PFS) was 2 months. Patients with brain parenchymal metastasis had poor 6 month OS (25% vs 50%, P = 0.013) and 6 month PFS (0% vs 20%, P = 0.023). Conclusion: A triple drug combination of methotrexate, cytosine arabinoside and hydrocortisone when given intrathecally for patients with LC showed good control of symptoms and reasonable survival. It may be beneficial in patients with no brain parenchymal involvement....

Large language models (LLMs) have rapidly emerged as transformative tools across multiple domains, including healthcare. The ability of LLMs to process vast amounts of data and generate human-like responses has facilitated their integration into patient care, particularly in enhancing communication, improving patient satisfaction, and streamlining administrative processes. Despite this potential, there are concerns regarding their accuracy, reliability, and ethical use in clinical settings. This scoping review aims to investigate and map the current literature on the use of LLMs in improving provider–patient experience and interaction efficiency. Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews guidelines, we conducted a systematic search of Ovid MEDLINE, PubMed, and Google Scholar databases to identify relevant articles published between January 2015 and June 2024. Of the 3568 articles initially screened, 47 satisfied the inclusion criteria. These articles spanned 13 countries and encompassed diverse healthcare settings. Thematic areas of LLM utilization included improving communication between patients and healthcare providers, resolving patient inquiries, enhancing patient education, and increasing operational efficiency. Although numerous studies have yielded positive outcomes, significant challenges related to data accuracy, hallucinations, bias, and ethical concerns remain. LLMs can considerably improve patient experience in healthcare, particularly in areas of communication, education, and administrative efficiency. However, concerns regarding accuracy, ethical implications, and the need for rigorous safeguards to prevent misinformation impede their widespread adoption. Future research should focus on developing context-specific LLMs tailored to healthcare environments and addressing the identified limitations to optimize their implementation in clinical practice.

Introduction In India, patients with gastric cancer present at an advanced stage, and there is no standard chemotherapy regimen. Al-Batran's fluorouracil, leucovorin, oxaliplatin, and docetaxel (FLOT) chemotherapy gave us a glimmer of hope. Objectives Hence, we intended to evaluate the efficacy of FLOT chemotherapy in locally advanced and metastatic adenocarcinoma of stomach. Materials and Methods In this single-center, prospective cohort, patients with locally advanced and metastatic gastric adenocarcinoma who required chemotherapy between March 2016 and November 2017 were included in the study. All patients received standard FLOT chemotherapy. The primary objective was to evaluate the safety and efficacy of FLOT chemotherapy in the Indian population. Overall survival (OS) and progression-free survival (PFS) were calculated through the plotted Kaplan–Meier curves. Results In our study, 28 patients received FLOT chemotherapy. Their mean age was 55 years (range, 28–70 years) with a male preponderance (89.3%). Twenty-five patients had metastatic disease (89.3%), and three had locally advanced disease (10.7%). The median number of cycles was 4.5 (range, 1–8), and 75% received at least four cycles (n = 21). The hematological toxicities exhibited were neutropenia (50%) and febrile neutropenia (35.7%). Sixteen (57.1%) patients needed dose modifications due to treatment-related adverse effects (AEs). AEs led to treatment discontinuation in seven (25%) patients after the first cycle. The overall response rate in the intent-to-treat population was 52.7%, with the best-obtained response being a partial response, median PFS of 5 months, and median OS of 13 months. Conclusion FLOT chemotherapy regimens induced excellent responses but with significantly increased toxicity, needing dose modifications, and hence, should be considered only in a young and fit patient. Nil. Publication Date: 08 March 2022 (online) © 2022. Indian Society of Medical and Paediatric Oncology. This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commercial purposes, or adapted, remixed, transformed or built upon. (https://creativecommons.org/licenses/by-nc-nd/4.0/) Thieme Medical and Scientific Publishers Pvt. Ltd. A-12, 2nd Floor, Sector 2, Noida-201301 UP, India