Diet impacts the pathogenesis of gastrointestinal diseases including inflammatory bowel diseases (IBD) and colorectal cancer (CRC). Although dietary protein can influence physiologic health, its impact on these diseases has not been adequately investigated. Consequently, clinical guidelines on optimal protein intake (i.e. amount and source) to help prevent or treat these conditions are limited. Recent preclinical and clinical studies have examined how modifying dietary protein can impact the pathogenesis of intestinal inflammation. For example, work in mice reveals that higher protein intake worsens colitis and that different dietary protein sources can exert differential effects on colitis severity. Microbial populations and their metabolism were shown to play an important role in mediating these effects. Studies in humans have shown that high intake of red meat is associated with increased IBD incidence and decreased time to relapse in patients with ulcerative colitis; however, it is unclear which other protein sources may be more beneficial. Although a direct connection between dietary protein and CRC has not been established, multiple preclinical studies have shown that reducing dietary protein exerts anticancer effects, including improved response to therapy across multiple tumor types. These effects were shown to be predominantly mediated by restricting tumors of exogenous growth-promoting amino acids, resulting in tumor stress, and in certain cases, activation of antitumor immunity. As a result of multiple studies, we have gained important insights into the role of dietary protein in mediating colonic inflammation and cancer. This work motivates clinical studies to directly test whether modifying source or amount of protein intake in patients with IBD or CRC will be beneficial for reducing disease severity and improving response to therapy.
Albumin plays a central role in maintaining circulatory and endothelial homeostasis through its oncotic and nononcotic effects. In cirrhosis, reduced concentration and impaired function of albumin contribute to circulatory derangements, renal dysfunction, and infection risk. While albumin is firmly established in certain settings such as spontaneous bacterial peritonitis (SBP), hepatorenal syndrome (HRS), and large-volume paracentesis (LVP), its broader use in cirrhosis remains controversial and incompletely defined. We aim to integrate up to date guidance on the use of albumin in cirrhosis, and to highlight areas where evidence remains limited or evolving. Evidence from randomized trials and meta-analyses highlights both established and emerging roles of albumin in cirrhosis. Albumin has demonstrated clear benefit after LVP, where it reduces postprocedural circulatory dysfunction, renal impairment, and hyponatremia compared with other plasma expanders. In HRS, albumin serves as an indispensable therapeutic backbone, enhancing the efficacy of vasoconstrictors and improving rates of renal reversal, yet its independent role remains incompletely defined. In SBP, co-administration of albumin with antibiotics reduces renal failure and improves short-term survival, establishing it as standard of care. In acute kidney injury (AKI) outside of HRS, current guidelines recommend the use of albumin as part of an initial volume challenge in many forms of AKI to aid diagnosis and potentially promote renal recovery, although the timing of its use differs among guidelines. Albumin is a cornerstone therapy in the management of decompensated cirrhosis and its clinical complications. While its role is well defined in HRS, SBP, and post-LVP, higher-quality evidence is needed to refine its use in other settings, particularly in AKI.
Intestinal ultrasound (IUS) as a noninvasive tool for assessment and longitudinal monitoring of inflammatory bowel disease (IBD) is gaining attention. This review examines current evidence supporting the diagnostic performance and utility of IUS in IBD and explores expanding applications, use in special populations, and remaining gaps in knowledge. Evidence supports its diagnostic accuracy in Crohn's disease (CD) and ulcerative colitis (UC). Bowel wall thickness (BWT) and vascularity through color Doppler signal (CDS) are among the most reliable markers of inflammation. IUS demonstrates utility for disease monitoring, assessment of treatment response, and prediction of long-term outcomes. Activity indices have been externally validated, demonstrating reproducibility. Beyond luminal assessment, transmural remission (TR) is emerging as a therapeutic target. Advanced techniques, including contrast-enhanced ultrasound (CEUS) and small-intestine contrast ultrasound (SICUS), may provide additional value in selected clinical scenarios, although their use remains limited to specialized settings. IUS is an important practical tool in IBD, complementing endoscopy and biomarkers. Although diagnostic performance is well established, future work should focus on IUS-driven treatment strategies, validation of meaningful endpoints, and addressing barriers to implementation.
Current inflammatory bowel disease (IBD) therapies mainly target immune pathways, yet many patients fail to achieve durable remission, highlighting the need to understand epithelial-intrinsic drivers of chronic inflammation and barrier defects. Recent single-cell, spatial, and functional studies have redefined secretory epithelial lineages as active regulators of mucosal immunity, microbial containment, and tissue recovery. Goblet cells are increasingly recognized as heterogeneous barrier sentinels whose region-specific alterations in mucus organization, microbial sensing, and stress responses can influence disease location and variability. Tuft cells are chemosensory hubs that connect luminal cues to type-2 and neuroimmune circuits, with evidence linking tuft-cell programs to repair-associated remodeling in inflammatory settings. Paneth cell dysfunction in ileal Crohn's disease frequently reflects disrupted antimicrobial and stress-adaptation programs, while colonic ulcerative colitis can exhibit injury-associated Paneth-like remodeling within the regenerative epithelium. Secretory epithelial lineages actively regulate mucosal immunity and barrier integrity through region-dependent programs that shift during chronic inflammation. Defining these lineage states and their signaling outputs can improve patient stratification and reveal epithelial-targeted therapeutic strategies that complement immunomodulatory treatment.
A substantial proportion of esophageal adenocarcinoma (EAC) and high-grade dysplasia (HGD) cases in Barrett's esophagus (BE) are diagnosed after a dysplasia-negative endoscopy before the next recommended surveillance interval. These are classified as postendoscopy esophageal carcinoma (PEEC) or postendoscopy esophageal neoplasia (PEEN) and represent critical failures of BE surveillance. This review summarizes current definitions, epidemiology, potential etiologies, and evolving strategies to reduce PEEC/PEEN and improve the quality of BE surveillance. High-quality endoscopic examination using high-definition white-light endoscopy (HD-WLE) and virtual chromoendoscopy (CE), adherence to the Seattle biopsy protocol, adequate inspection time, and training in the recognition of visible lesions harboring prevalent dysplasia/EAC, are critical in reducing PEEC/PEEN. Initial data on the use of adjunctive tools (wide-area transepithelial sampling) and molecular biomarkers (p53, DNA methylation panels, and Tissue Systems Pathology tests) demonstrate promising results for detecting prevalent dysplasia and for reducing PEEC and PEEN. BE surveillance quality metrics, such as cancer and neoplasia detection rates, have been shown to be inversely associated with PEEN. PEEC and PEEN reflect critical gaps in the effectiveness of BE surveillance. Improving the quality of endoscopic surveillance is essential, including meticulous mucosal inspection, appropriate use of advanced imaging techniques, and adherence to systematic biopsy protocols, to minimize missed neoplasia.
This review aims to summarize the recent developments in hypertriglyceridemic acute pancreatitis (HTG-AP) research in China, focusing on its increasing prevalence, pathophysiology, prognosis, and novel treatment strategies, emphasizing the relevance of these findings in clinical practice and research. Recent studies have highlighted a rising incidence of HTG-AP in China, especially among young males, linked to dietary and lifestyle changes. Key research has identified lipoprotein metabolism abnormalities and genetic factors as predictors of recurrence. Advances in treatment include the combination of low-molecular-weight heparin, insulin, and plasma exchange, showing improved outcomes compared to traditional methods. Additionally, the use of traditional Chinese medicine has shown promise in managing inflammation and improving patient recovery. These findings emphasize the importance of early diagnosis, personalized treatment strategies, and integrated approaches in managing HTG-AP. Chinese research has made significant strides in understanding the pathophysiology and treatment of HTG-AP, which may influence both national healthcare strategies and global management of the condition.
Malignant colorectal obstruction (MCO) is a common and life-threatening presentation of colorectal cancer, traditionally managed with emergency surgery associated with high morbidity and high stoma rates. Self-expanding metal stents (SEMS) have emerged as an important alternative for both palliation and as a bridge to curative resection. This review summarizes recent advances in indications, technical aspects, and emerging applications of colonic stenting, highlighting its role in modern multidisciplinary care. Current evidence supports the use of SEMS as one of the first-line palliative approaches in selected patients, providing rapid symptom relief and reducing the need for permanent stomas. In carefully selected patients, colonic SEMS can convert urgent high-risk operations into planned resections, facilitating minimally invasive approaches, though concerns remain regarding perforation risk and long-term oncologic outcomes. Increasing operator expertise, device innovation, and technical advances continue to improve safety and success rates. Beyond malignancy, expanding applications include refractory benign strictures, diverticular obstruction, and the use of lumen-apposing metal stents (LAMS) in inflammatory bowel disease and anastomotic complications. Colonic stenting has emerged as a valuable alternative to surgery for the management of MCO and is being investigated in select benign conditions, though broader adoption requires further evidence. Future research should refine patient selection, compare stenting with surgical alternatives, and clarify long-term outcomes.
The field of inflammatory bowel disease (IBD) continues to evolve at an unprecedented rate as the past decades have borne witness to the complete transformation of our approach to IBD and its care. Despite that, we continue to face major challenges, including rising incidence, shifting demographics, financial toxicity, as well as a frequently encountered therapeutic ceiling. This review aims to highlight the main factors driving the shifting landscape of IBD therapy. Many steps are being taken to improve efficacy and raise the therapeutic ceiling. Mounting evidence from clinical trials suggests that the use of various dual advanced therapies is well tolerated and may increase overall efficacy. Novel therapeutic mechanisms are being explored, including various novel oral agents as well as antihuman tumor necrosis factor-like cytokine A (anti-TL1A) antibodies with their novel antifibrotic potential. Delivery of care is also being optimized and refined with greater emphasis on early diagnosis, early effective therapy, treating to target and monitoring objective outcomes, therapeutic drug monitoring, and more effective use of current therapies. Greater recognition of the impact of IBD on patients beyond the disease itself is driving the spread of a patient-centric, multidisciplinary team-based approach to IBD care. As we continue to refine and deepen our understanding of IBD, the landscape of IBD therapy continues to shift and evolve as it aims to meet the needs of IBD patients with hope for brighter days ahead.
The complement system is one of the most evolutionarily conserved arms of innate immunity and has re-emerged as an important regulator of intestinal inflammation in inflammatory bowel disease (IBD). Early observations from the mid-1970 s such as complement deposition in diseased bowel tissue and elevated serum complement levels in patients with ulcerative colitis and Crohn's disease have evolved into a nuanced understanding of how individual complement components can exert both protective and pathogenic effects in IBD. This review highlights recent advances in complement biology and examines how complement shapes intestinal immune responses, particularly in the setting of ongoing inflammation. The complement system consists of more than 60 proteins that act as rapid first responders to infection. Although traditionally considered primarily liver-derived circulating effectors, recent work has demonstrated local synthesis and activation of key complement components at mucosal sites, including the colon. In parallel, genome-wide association studies have identified variants in complement genes associated with severe IBD complications. Collectively, these findings reveal a dichotomous role for complement in IBD, whereby excessive activation promotes inflammation, while impaired function compromises host defense and worsens disease outcomes. Complement-targeted therapies have been effective in other diseases but have not yet translated to IBD. A deeper understanding of context-dependent protective versus pathogenic complement functions will be essential for developing future therapeutic strategies.
The rising prevalence of obesity, now affecting over 40% of U.S. adults, poses critical implications for colorectal cancer screening, as obesity increases the risk of both colorectal adenomas and cancer. Despite these elevated risks, patients with obesity have lower colonoscopy screening participation and face unique barriers that compromise procedural quality. This review aims to highlight the challenges encountered during colonoscopy in obese patients and examine emerging solutions that may enhance screening effectiveness and patient outcomes. Obesity is associated with suboptimal bowel preparation, prolonged cecal intubation times, lower adenoma detection rates, and increased sedation-related complications. These challenges stem from altered gastrointestinal physiology, body habitus, and comorbid conditions. Recent innovations in bowel preparation strategies, sedation protocols, and endoscopic technologies-such as robotic-assisted colonoscopy and artificial intelligence-enhanced visualization-have demonstrated promise in addressing these limitations. Institutional initiatives, including tailored protocols and endoscopy team training, are also contributing to improved outcomes. As obesity rates climb, adapting colonoscopy practices to meet the needs of this population is essential. Incorporating evidence-based strategies and emerging technologies can help overcome procedural barriers, improve detection rates, and reduce disparities in colorectal cancer screening. Continued research and guideline refinement are needed to optimize care delivery for patients with obesity.
Pancreatic ductal adenocarcinoma (PDAC) has a dismal 13% 5-year survival rate, necessitating early detection and personalized treatment. This review evaluates whether germline genetic testing, integrated with clinical decision support (CDS) tools, is ready for widespread use in PDAC screening. We focus on its potential to identify high-risk individuals (HRIs) beyond those with strong family histories to complex risk and biomarkers, stratifying patients into low-risk and high-risk virtual populations for targeted surveillance. Germline genetic testing identifies pathogenic variants linked to hereditary cancer syndromes (HCS), enabling multiorgan surveillance and precision oncology (e.g., PARP inhibitors for BRCA2 mutations). Polygenic risk scores (PRS) combined with clinical markers like new-onset diabetes (NOD) increase the positive predictive value (PPV) for PDAC (e.g., 86.7% in high-PRS quintiles). Genetic testing also adjusts for biomarker variability (e.g., CA19-9 levels via FUT2/FUT3 genotyping) and optimizes chemotherapy through pharmacogenetics, reducing toxicity. Comprehensive platforms integrating genetic, clinical, and biomarker data enhance early detection and risk stratification. Genetic testing is ready for prime time in PDAC screening. It stratifies patients into low-risk (no surveillance) and high-risk (surveillance warranted) groups, improving early detection, outcomes, and cost-effectiveness, thus transforming PDAC prognosis through targeted intervention.
Despite significant progress in evidence-based therapies and models of care, hepatology continues to face challenges in translating proven interventions into routine clinical practice. Variability in adoption has contributed to ongoing gaps in quality, outcomes, and equity of care across diverse settings. Implementation science offers a systematic approach to understanding and improving how evidence-based interventions are delivered, adapted, and sustained in real-world environments. This review provides an overview of implementation science and discusses its increasing importance for advancing hepatology research and practice. Recent studies in hepatology have applied implementation science frameworks to better understand why effective interventions fail to reach patients and how those barriers can be addressed. Work in areas such as viral hepatitis elimination, cirrhosis management, palliative care integration, hepatocellular cancer surveillance, and alcohol use disorder treatment illustrates the value of focusing on context, stakeholder engagement, and strategy selection. These studies commonly use established frameworks, pragmatic trial designs, and mixed methods to assess outcomes such as adoption, fidelity, and sustainability alongside clinical impact. Implementation science offers a practical bridge between discovery and routine care in hepatology. Integrating implementation principles into research, quality improvement initiatives, and trainee education can accelerate the translation of evidence into practice, reduce unwarranted variation in care, and promote more equitable delivery of liver-related services.
Peroral endoscopic myotomy (POEM) is an established treatment for achalasia. Sacrificing the lower esophageal sphincter (LES) improves dysphagia but compromises the gastroesophageal junction (GEJ) barrier predisposing patients to acid reflux. Indeed, 40-60% of patients experience abnormal esophageal acid exposure post-POEM, while clinically significant reflux esophagitis (Los Angeles grade ≥B) is observed in 20-35%. Symptom-reflux discordance is common, necessitating objective assessment with upper endoscopy and/or ambulatory reflux testing using Lyon Consensus 2.0 criteria. Critically, anatomical evaluation must exclude alternative causes of perceived gastroesophageal reflux disease (GERD), including candida esophagitis, failed myotomy or recurrent achalasia, peptic stricture, and blown-out myotomy. Proactive intra-procedural strategies during POEM to minimize reflux have included limiting myotomy length, selective circular-layer myotomy, sling fiber preservation, anterior versus posterior approach selection, and endolumenal functional lumen imaging probe (EndoFLIP)-guided refinement of myotomy, though none has demonstrated consistent reflux reduction in randomized trials. Hybrid procedures combining POEM with endoscopic fundoplication (POEM+F/POEM-F) offer same session approaches that can significantly lower objective reflux up to 3 years. For proven post-POEM GERD, staged endoscopic options, transoral incisionless fundoplication, endoscopic full-thickness plication, and antireflux mucosectomy, offer symptom improvement and proton pump inhibitor (PPI) reduction in selected patients. A structured clinical pathway integrating proactive surveillance, objective confirmation, and individualized endoscopic intervention is proposed.
Autoimmune hepatitis (AIH) presenting with decompensated cirrhosis poses a major therapeutic dilemma for clinicians. Although the prompt initiation of immunosuppression (IS) can reverse disease activity and lead to the clinical resolution of decompensation, avoiding the need for liver transplantation (LT), it may also be futile or even harmful. International guidelines and cohort studies have begun to address this challenge, making it timely to synthesize available evidence and provide practical guidance for clinicians. Emerging data highlight that the benefit of IS in AIH-related decompensated cirrhosis is closely related to disease activity, as well as to the type and severity of decompensation. In this context, patients with "burn-out" cirrhosis, advanced hepatic encephalopathy and severely elevated prognostic scores have a low probability to benefit from IS and face a greater risk of developing treatment-related complications. Therefore, international guidelines emphasize individualized decision-making, integrating clinical scores and predictors of treatment benefit, as well as timely evaluation for LT. This review summarizes the current evidence and evolving recommendations for managing AIH-related decompensated cirrhosis, providing a structured approach to help clinicians identify candidates for IS and balance treatment decisions to optimize outcomes.
Small intestinal bacterial overgrowth (SIBO) has been a recognized condition for more than half a century. Early descriptions of SIBO were based on the concept of colonic bacteria "backing up" into the small intestine. This was based on techniques using unprotected aspiration catheters and earlier culture techniques. Recent advances in breath testing, small bowel sampling, culture techniques, and next generation sequencing have helped expand our understanding of SIBO. "SIBO" is now understood to encompass at least three different types of overgrowth including SIBO, intestinal methanogen overgrowth (IMO) and intestinal sulfide overproduction (ISO). Each has their own unique microbial profile. In addition, next generation sequencing has revealed that SIBO is not a migration of colonic flora into the small intestine, but rather overgrowth of two predominant species/strains from phylum Proteobacteria ( Escherichia coli and Klebsiella ). Lastly, results from next generation sequencing of the stool and small intestinal microbiomes have validated breath testing as a diagnostic tool. Together, these advances have allowed the identification of key microbes in overgrowth syndromes, uncovering their relationships to conditions such as irritable bowel syndrome, and paving the way for the development of novel customized treatment options in the future.
Colorectal cancer (CRC) is common and rising among persons under age 50, but screening uptake is sub-optimal, particularly in 45-49 year-olds. Death from CRC can be prevented through detection and removal of advanced precancerous colorectal lesions (APLS) or detection of CRC at an early stage. In this review, we cover average-risk CRC screening options and present a framework for test selection in different clinical settings. The optimal CRC screening test should be highly sensitive for APLs and early stage CRC, easy to access, affordable to patient and payers, and appropriate for screening settings. Organized screening is administered systematically on the population-level, while opportunistic screening relies on individual provider-patient shared decision making. In addition to established options such as fecal immunochemical testing, multitarget stool DNA testing, and colonoscopy, novel options include stool-based RNA testing, next-generation stool-based DNA testing, and blood-based DNA testing. Although blood-based tests may be convenient, their low sensitivity for APLs can unintentionally lead to negative consequences for CRC prevention. Uptake, cost, and efficacy of established and novel CRC screening tests influence the modality of choice for specific screening settings. Colonoscopy and stool-based tests should generally be first-line for CRC screening.
This review summarizes recent evidence on the use of glucagon-like peptide-1 (GLP-1) and glucagon-like peptide-2 (GLP-2) agonists in the management of short bowel syndrome (SBS), with a focus on emerging therapies and real-world experience. It evaluates their impact on intestinal adaptation, safety, and future clinical potential. GLP-2 agonists such as teduglutide continue to demonstrate improvements in intestinal absorption resulting in reductions in parenteral support (PS) requirements and improved quality of life. Clinical trials report that newer long-acting agents, such as apraglutide and glepaglutide, allow less frequent dosing with a reduction in PS and structural intestinal changes on imaging. Safety profiles remain favourable, with gastrointestinal symptoms, fluid balance issues, gallbladder events and injection-site reactions reported most frequently. GLP-1 agonists show promise in slowing transit time and offer an area for further research. While GLP-2 agonists shape the current landscape of SBS management, GLP-1 based therapies may complement future treatment strategies offering the potential to reduce or even eliminate dependence on PS. Continued long-term studies and registry data are essential to optimize patient selection, safety monitoring, and personalized use of GLP agonists.
Crohn's disease is a chronic, relapsing and remitting inflammatory process that can involve the entire length of the gastrointestinal tract. Upper gastrointestinal involvement (UGI) in Crohn's disease is present in up to 15% of patients and can present as a diagnostic challenge given nonspecific symptoms and overlapping disease entities. This review provides an update on diagnosing and risk stratifying UGI-CD. Literature suggests the use of imaging modalities (such as video capsule endoscopy, cross-sectional imaging and intestinal ultrasound) to help identify proximal inflammation when clinical suspicion for UGI involvement exists based on symptoms and patient factors. Additionally, proximal disease involvement has been associated with increased disease severity, a higher prevalence of strictures and an increased risk for surgery. First-line therapies are corticosteroids and antitumor necrosis factor therapies if systemic treatment is needed based on disease severity. For stricturing disease, endoscopic balloon dilation, strictureplasty, surgical resection or bypass can be considered for medically refractory or recurrent disease. As the prevalence and progression of UGI-CD is still understudied due to its variable definition, presentation and incidence, the development of a standardized approach to diagnosis could aid in determining the overall prevalence and most effective treatments.
This review summarizes recent advances in pancreatic ductal hypertension (PDH), emphasizing its pathophysiological mechanisms, clinical relevance across pancreatic diseases, and progress in noninvasive assessment. The aim is to highlight translational insights that may improve patient selection for intervention and guide long-term management strategies. Evidence indicates that PDH contributes not only to pain in chronic pancreatitis but also to exocrine insufficiency, diabetes, and complications such as post-ERCP pancreatitis (PEP) and recurrent acute pancreatitis (RAP). Pancreatic stellate cells (PSCs) are central to fibrosis and are directly activated by pressure, reinforcing disease progression. Traditional methods of measuring pancreatic duct pressure rely on invasive manometry, microtransducer catheters, or pancreatic fistulae, all with inherent risks. Recent translational advances, particularly magnetic resonance cholangiopancreatography (MRCP) integrated with computational fluid dynamics modeling, have demonstrated the feasibility of noninvasive pancreatic duct pressure (PDP) estimation with strong concordance to endoscopic retrograde cholangiopancreatography-based manometry and symptom relief. These advances emphasize the critical role of accurate pressure assessment in identifying patients with true ductal hypertension who are most likely to benefit from decompression. Noninvasive measurement offers a promising strategy to limit unnecessary interventions and to delineate the direct contribution of ductal pressure to exocrine, endocrine, and related disorders. Validation in larger cohorts and high-risk populations will be essential.
Small-bowel capsule endoscopy (SBCE) has transformed small-intestine diagnostics by enabling direct, noninvasive mucosal visualization. As healthcare systems increasingly prioritize value-based and sustainable care, this review explores recent advances in SBCE, focusing on home-delivery models, telemedicine, artificial intelligence (AI), and environmental impact. Life-cycle analyses estimate ~20 kgCO 2 per SBCE, ~18 kgCO 2 arising from patient travel. Transitioning from hospital attendance to home-delivery models can materially reduce this footprint. Feasibility studies report high acceptability for remote delivery, teleconsultation, and decentralized reading. AI-assisted reading platforms have recently shown significant reductions in reporting time, improving workflow efficiency. Rural modelling suggests travel emissions for colon capsule endoscopy (CCE) can exceed colonoscopy (~19.2 kgCO 2 e) but fall to ~5.3 kgCO 2 e with optimized courier logistics, despite >50% follow-up endoscopy rate. SBCE now stands at the nexus of technological innovation, clinical utility, and environmental accountability. Its journey from hospital corridors to home settings exemplifies a diagnostic paradigm built on accessibility, efficiency, and ecological integrity. Realizing this vision requires multicentre trials that incorporate life cycle, cost-effectiveness, and patient-reported outcomes. The capsule of the future will not merely image the intestine - it will symbolize medicine's evolution toward intelligent, zero-waste diagnostics.