The increasing detection of early gastrointestinal neoplasia and large precursor lesions across Western health systems has expanded the role of organ-preserving endoscopic therapies. Endoscopic mucosal resection (EMR). endoscopic submucosal dissection (ESD) and other related endoscopic resection techniques can provide curative-intent treatment with accurate histopathologic staging, but their safe and reproducible delivery depends on robust service design rather than technical expertise alone. This narrative review synthesizes practical insights from Western institutions on the development and operation of a high-quality endoscopic resection unit. Key domains include service model and referral pathways, patient selection and peri-procedural planning, procedural environment, equipment and accessories, multidisciplinary support, complication rescue pathways, workforce training, quality monitoring, and institutional sustainability. Particular emphasis is placed on standardization, multidisciplinary integration, prospective audit, and governance structures that support consistent outcomes and long-term program viability. High-quality resection units should be regarded not simply as procedural services, but as organized clinical platforms that deliver safe, scalable, and organ-preserving treatment, with resilience built within the team framework.
Endoscopic management of early oesophageal squamous cell carcinoma (ESCC) is progressively moving from a binary curative versus non-curative approach towards a risk-adapted strategy. Accurate optical assessment remains essential, but its limitations support the use of endoscopic resection, particularly endoscopic submucosal dissection (ESD), as both a therapeutic and a staging procedure. Compared with endoscopic mucosal resection, ESD provides higher en-bloc and complete resection rates, better histological assessment and lower local recurrence, although it requires dedicated expertise. Post-resection management should integrate depth of invasion, lymphovascular invasion, differentiation, margin status, comorbidities and patient preferences. Circumferential lesions represent a specific challenge because of the important risk of refractory stenosis. Definitive chemoradiotherapy remains a major organ-preserving option, either after non-curative ESD or as primary treatment, while salvage endoscopic therapy may be considered for selected superficial local failures. Multidisciplinary discussion is therefore central to balance oncological control, treatment morbidity and quality of life.
The gastrointestinal tract plays a key role in the control of appetite and food intake through upper gastrointestinal secretomotor function and release of gut peptides. The therapeutic efficacy of glucagon-like peptide-1 receptor agonists in the treatment of obesity, type 2 diabetes and several other non-communicable diseases linked to the metabolic syndrome, have established the validity of gastrointestinal signals as a target for the regulation of food intake. This review summarizes recent and ongoing research on luminal and systemic approaches to control appetite and food intake by modulating gastrointestinal signals. These modalities include luminal delivery of specific nutrients and tastants to alter gut peptide secretion, influence gastric accommodation or alter the occurrence of interdigestive gastric phase 3. Comparable effects can be achieved by a number of classical pharmaceutical approaches. The majority of studies are limited to short-term studies in healthy controls. Larger scale long-term studies in patient cohorts are now needed to evaluate the efficacy of these modalities to control appetite and food intake.
Metabolic dysfunction-associated steatotic liver disease has become the most common chronic liver disease worldwide, closely linked to obesity, insulin resistance, and type 2 diabetes mellitus. Liver steatosis is now recognized as the hepatic manifestation of systemic metabolic dysfunction rather than an isolated liver condition, with fibrosis progression driving long-term outcomes. As pharmacologic options remain limited, lifestyle therapy is central to management. This narrative review summarizes current evidence on the Mediterranean diet as a therapeutic strategy for obesity-related liver steatosis. Mechanistic and clinical data show that this dietary pattern targets key drivers of hepatic fat accumulation and cardiometabolic risk. Observational studies and randomized clinical trials demonstrate improvements in liver fat and metabolic parameters, often beyond those achieved with weight loss alone. The Mediterranean diet is safe, sustainable, and applicable in gastroenterology practice. Future priorities include standardized adherence metrics, longer outcome-driven trials, and precision nutrition approaches integrating metabolic and gut microbiota profiles.
Obesity represents one of the most pressing public health challenges worldwide, with its prevalence increasing dramatically over recent decades and contributing to metabolic diseases, including type 2 diabetes, cardiovascular disease, and non-alcoholic fatty liver disease. Although traditionally caused by an imbalance between energy intake and expenditure, obesity is now recognized as a multifactorial condition influenced by complex interactions. In this context, the gut microbiota—the diverse community of microorganisms inhabiting the gastrointestinal tract—has emerged as a possible new mechanism of host metabolism and energy homeostasis. Accumulating evidence indicates that individuals with obesity exhibit distinct alterations in gut microbiota composition, diversity, and metabolic activity compared with lean individuals. These changes may influence nutrient absorption, energy harvest, immune function, and inflammatory pathways, thereby contributing to metabolic dysfunction and excess adiposity. Furthermore, the gut microbiota is highly influenced by external factors, particularly diet, highlighting its potential as a modifiable target for therapeutic intervention. Understanding the relationship between gut microbiota and obesity may provide novel insights into disease mechanisms and help explain variability in treatment response. This review aims to summarize current evidence on microbiota alterations in obesity, underlying mechanisms, dietary influences, and emerging microbiota-targeted strategies for obesity management.
Endoscopic submucosal dissection (ESD) has transformed the management of superficial gastrointestinal neoplasia but remains technically demanding, with a steep learning curve posing significant training challenges, particularly in Western countries where case volumes are lower than in East Asia. This review summarizes current ESD training models including ex vivo and live animal models, simulation platforms, and traction devices. We examine learning curve evidence demonstrating that structured supervision reduces the learning curve from approximately 250 to 30-40 cases. Regional differences between Eastern and Western training paradigms are analysed. We propose a five-phase competency-based training pathway and identify priorities for future research including curriculum validation, artificial intelligence-assisted assessment, and scalable mentorship strategies.
Artificial intelligence (AI) is increasingly entering colonoscopy practice, with computer-aided detection (CADe) systems improving polyp and adenoma detection. However, the next challenge is not only to detect more lesions, but to determine in real time which lesions require resection, histopathological assessment, surveillance adjustment or surgical referral. Computer-aided diagnosis (CADx) systems aim to support this step by predicting colorectal polyp histology before resection and enabling optical diagnosis strategies such as “resect-and-discard” and “diagnose-and-leave”.The clinical value of CADx should not be judged by diagnostic accuracy alone. To become clinically meaningful, CADx must safely guide management decisions, meet established ASGE and ESGE thresholds, integrate into real-time workflow and remain valid across endoscopy platforms, imaging modalities, lesion subtypes and operator expertise. Although systems such as CAD EYE, GI Genius, POLAR and endocytoscopy-based algorithms show promising diagnostic performance, recent meta-analyses suggest that CADx has not yet provided clear incremental benefit for “diagnose-and-leave” or “resect-and-discard” strategies when added to endoscopist assessment. This may reflect high baseline confidence among endoscopists, but also current limitations including binary classification schemes, inconsistent handling of sessile serrated lesions, lack of calibrated confidence scores and limited explainability.Beyond diminutive-polyp characterisation, AI is also being explored for invasion-depth prediction in larger or suspicious colorectal lesions, where incorrect predictions may lead to undertreatment or overtreatment. Moreover, AI-assisted colonoscopy remains dependent on high-quality mucosal exposure, adequate bowel preparation, careful inspection and trained endoscopists. Overall, CADx remains promising, but broader implementation requires prospective real-world validation, explainable and interoperable systems, robust human-AI interaction and clinically relevant outcomes before it can safely substitute histopathology in selected settings.
The gastrointestinal microbiome has emerged as a critical interface between environmental exposures and host biology, shaping carcinogenesis, tumor behavior, and therapeutic responsiveness across digestive tract malignancies. This narrative review synthesizes current evidence on microbiome testing in esophageal, gastric, colorectal, hepatobiliary, pancreatic, and gastrointestinal stromal cancers, highlighting microbial signatures, emerging translational applications, and the methodological challenges that currently limit clinical implementation. Tumor-specific microbial alterations are considered alongside the broader functional consequences of dysbiosis, including its roles in genotoxicity, immune modulation, and metabolic reprogramming. Particular attention is given to the influence of the microbiome on systemic therapies, especially immune checkpoint inhibition, where microbial diversity, compositional signatures, and antibiotic exposure have been associated with differences in treatment efficacy. Emerging mechanistic insights are highlighted, including the role of microbiota-derived metabolites as key mediators of host-tumor immune interactions. The review further discusses microbiome-directed interventions, including fecal microbiota transplantation and dietary modulation, while critically evaluating the barriers to their clinical translation. Although microbiome profiling has considerable potential to improve risk stratification and therapeutic personalization, current evidence remains largely associative or based on early-phase clinical studies, and no microbiome-based testing strategy has yet been validated for routine clinical use beyond Helicobacter pylori eradication for gastric cancer prevention. Large prospective studies, standardized methodologies, and interventional clinical trials are required before microbiome testing can be integrated into routine precision oncology.
Rising global trends in obesity have led to increased prevalence of fatty liver disease known as nonalcoholic fatty liver disease (NAFLD). The previously used, stigma-associated term has been replaced by updated nomenclature—first, metabolic dysfunction–associated fatty liver disease (MAFLD) and subsequently metabolic dysfunction–associated steatotic liver disease (MASLD). This modification reflects a more accurate understanding of disease pathophysiology and removes the emphasis from severe alcohol consumption, while introducing diagnostic criteria centered on metabolic dysfunction. This review also describes related clinical entities like metabolic dysfunction–associated steatohepatitis (MASH) and steatotic liver disease (SLD). Global trends in obesity indicate a continuous rise in prevalence, accompanied by an increasing burden of SLD in both adults and pediatric population. Projections suggest that by 2040, more than half of the global population may be affected by both obesity and SLD, highlighting the need for non-invasive diagnostics, effective targeted therapy and structured follow up strategies. Drugs for obesity management like semaglutide and tirzepatide demonstrated clinical improvement primarily through beneficial metabolic effect, highlighting common basis of treatment of obesity and SLD. Although several liver-targeted therapies are currently under investigation, resmetirom represents the first approved pharmacologic agent available on the market. However, lifestyle modification remains significant part of treatment. Looking ahead, field of greatest potential is pharmacotherapy with certain molecules currently under phase 2 and phase 3 clinical trials. Importantly, shared pathophysiologic mechanisms linking obesity, metabolic syndrome and MASLD must not be overlooked in suspicion, diagnosis and treatment of liver diseases.
Pancreatic cancer remains one of the most lethal malignancies and is projected to become the second leading cause of cancer-related mortality in the United States by 2030. Although pancreatic ductal adenocarcinoma (PDAC) constitutes the vast majority of exocrine pancreatic tumors, rare histological variants, most notably primary squamous cell carcinoma of the pancreas (PSCC) and pancreatic adenosquamous carcinoma (PASC), pose distinct diagnostic and therapeutic challenges. PSCC and PASC account for approximately 0.005% to1.13% of all pancreatic cancers, with PASC occurring more frequently than pure PSCC. Notably, population-level data indicate that the incidence of PSCC tripled in the last two decades. Diagnosis and management are guided by poor evidence, primarily coming from retrospective case series, and there are currently no practice guidelines for these subtypes. The high frequency of advanced-stage presentation limits eligibility for potentially curative resection to ∼10% of patients. In the metastatic setting, retrospective series suggest modest efficacy of systemic therapy, primarily with chemotherapy regimens such as FOLFIRINOX and gemcitabine plus nab-paclitaxel. In contrast, available evidence does not demonstrate a clear survival benefit from adjuvant chemotherapy. This review synthesizes current evidence on diagnosis, classification, molecular characteristics, and therapeutic management of PSCC and PASC, and outlines priorities for multicenter registries to improve understanding and outcomes in these extremely rare pancreatic cancer subtypes.
Background and aims Advanced rectal lesions (ARLs), including large laterally spreading lesions (LSLs), villous or high-grade dysplastic adenomas, and early rectal cancers, constitute a critical transitional category between benign adenoma and invasive carcinoma. Historically, radical surgery was liberally employed for these lesions, often resulting in significant morbidity and permanent stoma formation. Contemporary endoscopic and transanal techniques permit curative resection while preserving anorectal function, but careful assessment is mandatory to avoid undertreatment of covert cancers. Methods We reviewed international guidelines and key studies on ARL assessment and management, focusing on endoscopic imaging, staging modalities and therapeutic techniques. Evidence from ESGE, ASGE, NCCN and BSG/ACPGBI guidelines, prospective trials, and observational cohorts was appraised and summarized. Points of divergence between society guidelines are highlighted where relevant to rectal lesion management. Results The rectum has distinct anatomical and vascular characteristics which strongly influence endoscopic and surgical decision making. Lesions in the rectum have a higher risk of submucosal invasive cancer (SMIC) compared to the remainder of the colon andare more likely to be larger, nodular and villous in nature. Rectal surgery is complex and has a higher risk of stoma formation and adverse events than colon surgery. Appropriately selected organ preserving techniques reduce risk and preserve function for patients.High-definition white-light endoscopy with virtual or dyebased chromoendoscopy permits accurate optical diagnosis of ARLs. Assessment of surface features and morphology allows the endoscopist to predict the risk of covert cancer. Routine biopsy is discouraged to avoid fibrosis. Endoscopic ultrasound and pelvic MRI are used selectively for lesions suspicious for deeper invasion or when planning transanal surgery.Endoscopic resection is appropriate for the majority of lesions in the rectum and a selective strategy ensures that the appropriate technique can be chosen to optimize oncological outcomes. Lesions with features of deep invasive cancer should be carefully appraised and discussed in a multidisciplinary setting. Selected lesions with a low risk of covert cancer may be resected by endoscopic mucosal resection (EMR) with margin ablation. Endoscopic submucosal dissection (ESD) provides superior en-bloc and curative resection rates for higher risk lesions. Emerging data demonstrates that ESD has equivalent or superior outcomes compared to transanal endoscopic microsurgery (TEM), or transanal minimally invasive surgery (TAMIS) for larger rectal lesions. Hybrid techniques (e.g., underwater EMR, tip-in EMR, full-thickness resection devices) may also be utilised in the therapeutic framework. Conclusions An evidence-based, organ-preserving algorithm for ARLs emphasizes optical risk stratification, individualised technique selection and multidisciplinary input to optimize patient outcomes. Ongoing research will refine hybrid methods, artificial intelligence-aided diagnostics and new organ preserving strategies.
Endoscopic submucosal dissection (ESD) is an effective organ-sparing technique for superficial neoplasia in the upper gastrointestinal tract, although it remains associated with a non-negligible risk of complications. This narrative review provides an integrated overview of the entire ESD pathway, from pre-procedural risk stratification to intraprocedural management and post-procedural care.Adverse events should be interpreted as the result of the interaction between patient-related factors, lesion characteristics, and procedural complexity. During the procedure, maintaining stable control of the submucosal plane is central; in this context, strategies such as anticipatory vessel coagulation, optimized dissection, traction, and saline immersion contribute to improve visualization and reduce bleeding and perforation risk.Post-procedural risk is largely site-specific, with stricture predominating in the esophagus, delayed bleeding in the stomach, and both bleeding and perforation in the duodenum. A risk-adapted approach is therefore essential to improve safety and optimize outcomes.
Obesity is increasingly recognized as an immunometabolic disorder in which chronic low-grade inflammation is sustained by persistent upstream triggers rather than by adiposity alone. A central candidate trigger is intestinal barrier dysfunction with metabolic endotoxemia, defined as chronic, subclinical elevations of gut-derived microbial components, most notably lipopolysaccharide (LPS), in the absence of overt infection. In obesity, the intestinal barrier shifts toward increased functional permeability through coordinated remodeling of tight junction organization, mucus layer destabilization, and epithelial stress responses. This creates permissive conditions for microbial ligand passage while mucosal architecture can remain grossly intact. Importantly, systemic exposure is not determined solely by permeability, but by a coupled system involving luminal LPS availability, lipid-facilitated epithelial uptake and export, and context-dependent partitioning and clearance of LPS through binding proteins, lipoproteins, and hepatic handling. Low-dose, repeated LPS signaling engages innate immune pathways (including TLR4 and inflammasome-associated programs), amplifying cytokine production and stress kinase activity that impairs insulin signaling across metabolic tissues. The resulting organ crosstalk within the gut-liver-adipose axis helps explain heterogeneity in metabolic trajectories among individuals with comparable body mass index, particularly when visceral adiposity and postprandial lipid flux are considered. Therapeutic strategies that converge on this axis, including dietary fiber enrichment, microbiota-targeted interventions, metabolic pharmacotherapy, and bariatric procedures, provide proof of reversibility, yet human evidence remains limited by methodological heterogeneity and incomplete causal inference. Advancing the field will require standardized, dynamic barrier phenotyping, longitudinal designs, and stratified intervention trials to identify gut-driven subgroups and enable precision approaches to obesity-related cardiometabolic disease.
Barrett's esophagus-related neoplasia is now predominantly managed with endoscopic eradication therapy. This strategy combines endoscopic resection of visible lesions with ablation of residual Barrett's mucosa, offering excellent safety and long-term disease control. Two endoscopic resection techniques are used in current practice: endoscopic mucosal resection and endoscopic submucosal dissection. Existing guideline recommendations for technique selection vary but are largely based on the suspected depth of invasion and preference for R0 resection. However, the unique biological and clinical features of Barrett's challenge this framework. Neoplasia arises within a field of metaplastic change, and the ultimate goal is not simply complete resection but durable eradication of disease. The traditional oncologic endpoint, R0 resection, may be less meaningful in this context, while more clinically relevant outcomes, such as recurrence, disease-free survival, and patient-centred measures, remain inconsistently defined and reported. Furthermore, technical and procedural considerations, including histopathological accuracy, safety, and resource use, add further complexity to decision-making. This review explores the evolving evidence, highlights ongoing debates in technique selection for Barrett's neoplasia, and proposes considerations to inform patient-centred clinical decision-making and future research priorities.
This review summarizes how aging-related changes in the gut microbiome contribute to gastrointestinal carcinogenesis. We highlight that cancer risk in aging is shaped not only by chronological age but largely by diet, lifestyle, environment, and their impact on microbial ecology. In healthy aging, microbial diversity is preserved with functional redundancy among short-chain fatty acid-producing commensals that support barrier integrity, immune regulation, and metabolic homeostasis. In unhealthy aging, loss of beneficial taxa, expansion of pathobionts, and accumulation of pro-inflammatory and genotoxic metabolites promote chronic inflammation, epithelial dysfunction, and DNA damage, thereby facilitating tumour development. Key microbial drivers include pks + Escherichia coli, enterotoxigenic Bacteroides fragilis, and Fusobacterium nucleatum, acting through genotoxic, inflammatory, and immune-evasive mechanisms. Although microbiome-targeted interventions such as diet modification, probiotics, faecal microbiota transfer, and phage-based strategies are promising, current evidence remains largely preclinical or observational. Overall, the gut microbiome is a central, modifiable mediator of aging-associated gastrointestinal cancer risk, but longitudinal studies are needed to establish causality and therapeutic efficacy.
Colorectal endoscopic submucosal dissection (ESD) is gaining adoption in Western practice because it outperforms endoscopic mucosal resection (EMR), with higher en bloc and R0 resection rates, lower local recurrence, and less need for surgery. Its main limitation is technical: colorectal ESD is long, complex, and complication-prone. Multiple recent advances aim to improve reproducibility and safety, including new dissection strategies (pocket-creation, tunneling, underwater ESD), traction systems (clip-band, adaptive and magnetic traction), advanced knives (a novel thin-needle knife with high-pressure waterjet) and closure platforms (reopenable clip with anchor prongs, through-the-scope helix tack-and-suture system and endoscopic hand suturing), stabilizing platforms, and robotic and AI assistance. Safe ESD still depends on fundamental skills: tip control, stable incision and trimming, efficient submucosal dissection, and immediate control of bleeding and perforation. This review aims to summarize current technical solutions, identify persistent limitations, and define priorities for training, case selection, cost-effectiveness, and environmental impact in Western practice.
Biliary tract cancers (BTC) are a diverse group of aggressive malignancies with a growing global prevalence and a persistently poor prognosis. Over the past decade, substantial evolution in systemic therapy has transformed the therapeutic landscape for advanced disease. Gemcitabine–cisplatin remains the mainstay of first-line treatment, but the incorporation of immune checkpoint inhibitors — most notably durvalumab and pembrolizumab — has set new standards of care, providing long-term survival benefits across BTC subtypes. In later lines of treatment, the benefit of cytotoxic chemotherapy is modest, though FOLFOX and liposomal irinotecan combinations can offer limited improvements in selected patients. Alongside these incremental advances, major progress has beendriven by molecularly targeted therapies. Actionable genomic alterations, including FGFR2 fusions, IDH1 mutations, HER2 amplification, BRAF V600E mutations, NTRK fusions, and rare KRAS G12C alterations, enable the use of highly effective tumour-agnostic or tumour-specific agents. Next-generation sequencing, ideally incorporating both DNA and RNA profiling, is therefore essential in the modern management of BTC. Locoregional therapies, including selective internal radiation therapy (SIRT) and hepatic arterial infusion (HAI), may enhance tumour control further and occasionally enable secondary resection, particularly in cases of liver-limited intrahepatic cholangiocarcinoma. Continued advances in biomarker-driven therapy and an improved understanding of resistance mechanisms and multimodal integration will be crucial in achieving meaningful survival improvements in this challenging disease.
Pancreatic cystic lesions have been increasingly detected with the widespread use of cross-sectional imaging. As these lesions are heterogeneous, differentiating benign from (potentially) malignant cystic lesions is important as well as challenging. Endoscopic ultrasound assessment, combined with cyst fluid analysis, forms the cornerstone of the diagnostic algorithm. Biochemical markers such as carcinoembryonic antigen (CEA), amylase, and glucose have been shown to distinguish mucinous from non-mucinous cystic lesions. Each parameter has its own advantages and its own limitations. Novel molecular markers, such as DNA-based assays and next-generation sequencing, have shown promise. The various guidelines have incorporated cyst fluid analysis in their recommendations. A standardized multimodal approach is essential, incorporating all aspects. This review synthesizes evidence on the utility of endoscopic ultrasound (EUS)-guided cyst fluid analysis in the management of pancreatic cystic lesions.
Pancreatic cystic lesions are increasingly detected in routine practice, yet their management remains difficult because diagnosis is often presumptive, malignant potential is heterogeneous, and pancreatic surgery carries substantial morbidity. This review critically compares the major international guidelines for mucinous pancreatic cystic lesions, focusing on diagnostic strategy, indications for surgery, operative management, surveillance, postoperative follow-up, and the risk of concomitant pancreatic ductal adenocarcinoma. Across guidelines, broad agreement exists on the central role of MRI/MRCP, the selective use of EUS, and the need to individualize decisions according to surgical fitness. However, important differences persist regarding the weight assigned to worrisome features, the role of contrast-enhanced EUS and cytology, thresholds for surgery, and the possibility of stopping surveillance. Recent evidence supports a more risk-adapted approach for selected low-risk branch-duct IPMNs, but the practical application of guidelines remains limited by divergent frameworks, modest evidence quality, and unequal access to advanced diagnostics. Overall, the field is moving toward more multimodal and individualized care, while still requiring stronger evidence and greater pragmatism to improve real-world applicability.
