An important regulator of tumor immunosurveillance and innate immune activation in gastrointestinal (GI) malignancies is the cyclic GMP-AMP synthase-stimulator of interferon genes (cGAS-STING) pathway. The release of type I interferons, dendritic cell (DC) maturation, and cytotoxic T lymphocyte recruitment are the final steps of a pathway that is typically set in motion by aberrant DNA damage, microbiome-derived DNA, or mitochondrial stress. Tumour has it that immunologically "cold" gastrointestinalcancers can be made more sensitive to immune-checkpoint blockade (ICB), radiation, and chemotherapy by therapeutically activating the cGAS-STING pathway, which turns them into inflamed, T-cell-permissive niches. Progress in nanomedicine, small-molecule STING agonists, and tumour-microenvironment-responsive drug delivery systems has broadened the translational scope of this pathway across colorectal, gastric, and pancreatic malignancies. However, tumour-intrinsic heterogeneity, the dual immunostimulatory and immunosuppressive functions of chronic STING signalling, and delivery-related toxicities continue to pose substantial challenges. This review consolidates current mechanistic insights, preclinical evidence, and emergent clinical data regarding the cGAS-STING pathway in gastrointestinal cancers, while emphasising biomarker-guided patient stratification and AI-powered predictive tools that could facilitate the precise application of STING-targeted therapies.

Gallbladder cancer (GBC) is associated with a poor prognosis due to the challenges in early diagnosis. The gallbladder's anatomical constraints make it difficult to obtain tumor tissue for histological analysis and diagnostic monitoring. Consequently, liquid biopsy (LB) has emerged as a vital technique for minimally invasive extraction of tumor-derived materials. This review explores various non-invasive methods for GBC screening, with a particular focus on liquid biopsy. A comprehensive search was conducted on PubMed, Scopus, Web of Science, and Google Scholar for articles published from 1994 to 2025. The key search terms were "Gallbladder cancer", Liquid biopsy" "cfDNA", "ctDNA", "CTCs", "Exosomes" and "Clinical trial". Relevant articles on the subsections were included in this narrative literature review. Liquid biopsy, one of the most promising and innovative diagnostic tools, was analyzed in detail, including its application in clinical studies for GBC. Despite its challenges, and varied results, this method shows potential for early GBC detection and treatment. Tissue specimens often fail to capture the dynamic evolution of cancer genomes and the genetic heterogeneity of metastatic cancers, while liquid biopsies, being more sensitive than cytology, can enhance the diagnosis and monitoring of GBC at various stages. This approach, thus, harbors the potential to facilitate cancer genetic profiling, paving the way for precision oncology strategies.

To identify randomised control trials (RCTs) of treatments (recommended by the National Comprehensive Cancer Network (NCCN), the European Society for Medical Oncology (ESMO) Clinical Practice Guidelines and clinical expertise) for the second- or later-line treatment of advanced/metastatic gastric cancer. To determine the relative efficacy and safety of the treatments. RCTs were identified from a Rapid Literature Review and a published systematic review. Identified RCTs were subject to data-extraction and narrative review. Eligible RCTs were included in evidence networks to determine relative efficacy and safety of the treatments. In total, 44 RCTs (pertaining to eleven treatments), were identified for data-extraction and narrative review; 37 in the second-line setting, five in the second- and later-line setting and two in the third- and later-line setting. Evidence networks were feasible for the second-line treatments only. No statistically significant differences, across treatments, for key efficacy outcomes (overall-survival, progression-free survival), and additional outcome (objective-response rate) were identified. Pembrolizumab was associated with a statistically significant decreased risk of Grade ≥ 3 treatment-related adverse effects versus paclitaxel; no other significant differences, across treatments, were identified for this outcome. The appreciable number of RCTs identified indicates that the treatment landscape here is rapidly evolving. The introduction of novel treatments, in the second-line setting, has not had a statistically significant impact on key efficacy outcomes, and has had little impact on safety outcomes, versus more established treatments. There remains a need for novel treatments that will have a significant benefit on efficacy and safety outcomes.

Pancreatoduodenectomy (PD) remains the cornerstone surgical treatment for resectable periampullary and pancreatic malignancies, with improving survival due to advances in oncologic surgery and perioperative management. Emerging evidence, however, identifies metabolic dysfunction-associated steatotic liver disease (MASLD) as a relevant postoperative complication that may adversely influence long-term outcomes. This review aims to summarizethe incidence, pathophysiology, clinical implications, and management strategies of de novo MASLD following PD in patients with gastrointestinal malignancies. A narrative review of clinical and translational studies was conducted focusing on hepatic steatosis, metabolic derangements, pancreatic exocrine and endocrine insufficiency, and chemotherapy-related liver injury after PD. Particular attention was given to studies evaluating postoperative nutritional status, liver-related morbidity, and implications for oncologic therapy. De novo MASLD develops in approximately 8-37% of patients within the first year after PD. Unlike classical metabolic MASLD, postoperative disease is predominantly driven by exocrine pancreatic insufficiency, malabsorption, intestinal dysbiosis, and altered gut-liver signaling, leading to hepatic lipotoxicity and inflammation. Progression to metabolic dysfunction-associated steatohepatitis, fibrosis, or cirrhosis has been reported, potentially limiting tolerance to adjuvant chemotherapy. Early pancreatic enzyme replacement therapy improves nutritional parameters and may reduce hepatic steatosis, while duodenum-preserving pancreatic head resection appears to attenuate metabolic sequelae. MASLD represents a distinct and clinically significant postoperative complication following PD with potential impact on oncologic outcomes. Systematic hepatic monitoring and multidisciplinary management should be integrated into postoperative care pathways for patients with gastrointestinal cancers.

To assess how obstructive jaundice and socioeconomic determinants (residence, literacy, gender) affect treatment initiation and curative surgical eligibility among patients with gallbladder cancer in North India. In this prospective observational cohort, adults with radiological or histological gallbladder cancer presenting between September 2023 and May 2024 were enrolled at a tertiary cancer centre. Baseline demographics, stage, obstructive jaundice status, biliary drainage (PTBD/ERCP), treatment initiation, and surgical eligibility were recorded. Associations were examined using chi-square and relative risk, followed by multivariable logistic regression including variables with p < 0.10. Of 1,500 enrolled patients, 1,409 were evaluable; 643 (45.6%) had obstructive jaundice. Treatment non-initiation occurred in 330/643 (51.3%) with obstructive jaundice versus 24/766 (3.1%) without obstructive jaundice (p < 0.001). Curative surgery was feasible in 51/643 (7.9%) with obstructive jaundice compared with 223/766 (29.1%) without obstructive jaundice (RR 0.27; 95% CI 0.20-0.36). Illiteracy (57.6%) and rural residence (69.4%) predominated. On multivariable analysis, independent predictors of treatment non-initiation were obstructive jaundice (aOR 11.2; 95% CI 7.6-16.5), metastatic disease at presentation (aOR 3.9; 95% CI 2.1-7.4), rural residence (aOR 2.7; 95% CI 1.9-3.9), and illiteracy (aOR 1.8; 95% CI 1.3-2.6). Obstructive jaundice and socioeconomic disadvantage synergistically drive early care discontinuity and reduce curative opportunities in gallbladder cancer, supporting decentralized decompression, patient navigation, and socioeconomic support in high-incidence regions.

Semaglutide, a glucagon-like peptide-1 receptor agonist (GLP-1 RA), is increasingly used for glycemic control, weight loss, and cardiovascular risk reduction. While GLP-1 RAs are commonly associated with acute pancreatitis, emerging reports suggest a possible association with pancreatic cystic lesions, even in patients without typical risks factors such as alcohol, gallstones, or hereditary syndromes. We present two cases of middle-age female patients without prior compline or pancreatic disease who developed large distal pancreatic mucinous cystic neoplasms following GLP-1 Ras use. Both underwent imaging and aspiration, which revealed elevated carcinoembryonic antigen (CEA) levels. Surgical management consisted of distal pancreatectomy and splenectomy. Pathology confirmed MCN with no malignancy. Both patients had uneventful recovery. These two cases suggest a possible association between GLP-1 receptor agonists, and the development of pancreatic mucinous cystic neoplasms (MCNs) in patients without prior pancreatic disease or conventional risk factors. While causality cannot be established, the temporal relationship, absence of alternative etiologies, and supportive literature suggest a possible drug-related effect. Preclinical studies have implicated GLP-1 RAs in pancreatic ductal hyperplasia and cyst formation, and recent clinical reports reinforce these findings. As semaglutide use expands, clinicians should be vigilant for structural pancreatic changes, and further studies are warranted to elucidate underlying mechanisms and clinical implications. These cases raise concern regarding a potential association between semaglutide therapy and mucinous cystic neoplasms. Increased vigilance and further observational studies are warranted to evaluate this potential adverse effect.