Senescence is an irreversible cell cycle arrest -characterized by morphological alterations, genomic instability and secretome changes- that profoundly affects the tissue structure and function. Accumulating evidence indicates that senescence plays a relevant role in gastrointestinal pathologies: senescence contributes to salivary gland hypofunction, is instrumental in the development of oral sub-mucous fibrosis, drives age-dependent hepatic steatosis and regulates the clinical progression of steatotic liver disease. Senescence in the biliary tract develops in response to ischemic injury in biliary complications and is characteristic of biliary conditions such as biliary atresia, primary sclerosing cholangitis and primary biliary cirrhosis. Senescence also contributes to acute pancreatitis and plays a major role in the dysfunction of pancreatic beta cells. Moreover, senescence is a hallmark of a number of gastrointestinal conditions such as inflammatory bowel disease and colorectal cancer. These examples illustrate the widespread effect of cellular senescence in the gastrointestinal tract, not just as a consequence of the disease, but as a driver of pathology and a potential therapeutic target. In this review we describe the mechanisms, hallmarks and consequences of cellular senescence, as well as the therapeutic potential of senescence-targeting interventions. We aim to highlight the importance of understanding the molecular basis of senescence in gastroenterology, whilst connecting the worlds of research and clinical practice.

Gastrointestinal (GI) clinicians are a critical touchpoint for individuals at risk for genetic and familial syndromes that increase risk of colorectal, gastric and pancreatic cancer. While advances in sequencing technology and reduced costs have made genetic testing more readily accessible to clinicians and even to patients through direct-to-consumer testing, uptake of genetic testing remains underutilized. This is a missed opportunity to identify patients and family members who could benefit from genetic testing to diagnose cancer susceptibility syndromes for which surveillance and preventive interventions exist. Barriers for integration of genetic testing in routine practice include lack of awareness about genetic conditions by patients and providers, concerns about genetic testing costs and implications for insurability, as well as challenges in implementing algorithms for risk assessment and coordinated care in complex medical systems. This review addresses current evidence and guidelines for cancer risk assessment, genetic testing and management to enable GI clinicians to identify and care for individuals with genetic cancer-predisposition syndromes in routine practice.

In a treat to target era, objective disease assessment in inflammatory bowel disease (IBD) has become increasingly important. For many years, endoscopy has been generally accepted as the gold standard for evaluating the bowel mucosa, additionally facilitating biopsy. However, non-invasive disease assessment is now increasingly demanded and cross-sectional imaging techniques as well as video capsule endoscopy have markedly improved. Emerging evidence demonstrates the added clinical value of transmural assessment both in Crohn's disease and ulcerative colitis, and cross-sectional imaging modalities are increasingly used in phenotyping and monitoring IBD patients. In the current review we propose potential algorithms to use non-invasive imaging in various clinical scenarios and for use in daily practice. The readers will come away with an understanding of what imaging they should consider for different clinical situations and the strengths and limitations of each modality. Future developments of non-invasive diagnostic strategies and areas in need of further research are highlighted.

The prognostic significance of the Platelet-to-Lymphocyte Ratio (PLR) in patients with hepatocellular carcinoma (HCC) undergoing treatment with immune checkpoint inhibitors (ICIs) remains uncertain. A systematic review and meta-analysis was conducted to assess the prognostic value of PLR in HCC patients receiving ICIs.

Monogenic inflammatory bowel disease (mIBD) in patients with onset after the age of 16 has been increasingly recognized, but these reports are sporadic and lack a systematic overview, leaving the clinical and genetic characteristics poorly understood. This study aimed to characterize these late-onset mIBD (LO-mIBD), using an infantile-onset population as a control.

Neoadjuvant chemotherapy (NC) is a cornerstone in the management of resectable esophageal squamous cell carcinoma (ESCC). The integration of PD-1/PD-L1 inhibitors into NC (NIC) regimens has shown promise; however, its efficacy and safety remain uncertain. This meta-analysis aims to compare the potential risks and clinical benefits of NIC versus NC in patients with resectable ESCC based on randomized controlled trials (RCTs).

Existing studies have explored the association between immune-inflammatory indices and inflammatory bowel disease (IBD), but there is a lack of comprehensive evidence. This meta-analysis and systematic review seeks to synthesize the data of available clinical research and offer the latest and comprehensive evidence-based conclusions regarding whether these immune-inflammatory indices can effectively predict the severity, activity, and prognosis of IBD.

Several studies revealed that synbiotics have been beneficial in managing non-alcoholic fatty liver disease (NAFLD), but the findings are conflicting. We aimed to assess the effect of synbiotic supplementation on cardiovascular risk factors in patients with NAFLD.

Rectal resection could potentially cause low anterior resection syndrome (LARS). Although recent studies have reported the efficacy of enema against LARS, no systematic review and meta-analysis has been conducted.

There is a large heterogeneity among individuals in their therapeutic responses to the same drug and in the occurrence of adverse events. A key factor increasingly recognized to contribute to this variability is the gut microbiome. The gut microbiome can be regarded as a second genome, holding significant metabolic capacity. Consequently, the field of pharmacomicrobiomics has emerged as a natural extension of pharmacogenomics for studying variations in drug responses. Pharmacomicrobiomics explores the interaction of microbiome variation with drug response and disposition. The interaction between microbes and drugs is, however, complex and bidirectional. While drugs can directly alter microbial growth or influence gut microbiome composition and functionality, the gut microbiome also modulates drug responses directly through enzymatic activities and indirectly via host-mediated immune and metabolic mechanisms. Here we review recent studies that demonstrate the interaction between drugs and the gut microbiome, focusing on cancer immunotherapy and immunomodulation in the context of inflammatory bowel disease and solid organ transplantation. Because the gut microbiome is modifiable, pharmacomicrobiomics presents promising opportunities for optimizing therapeutic outcomes, with recent clinical trials highlighting fecal microbiota transplantation as a strategy to enhance the efficacy of immune checkpoint blockade. We also shed light on the future perspectives for patients arising from this field. Although multiple lines of evidence already demonstrate that the gut microbiome interacts with drugs, and vice versa, thereby affecting treatment efficacy and safety, well-designed clinical studies and integrated in vivo and ex vivo models are necessary to obtain consistent results, improve clinical translation, and further unlock the gut microbiome's potential to improve drug responses.

Colorectal cancer (CRC) is a common malignant tumor. Immune checkpoint inhibitors (ICIs), particularly those targeting programmed cell death protein 1(PD-1) and programmed cell death ligand 1(PD-L1), have shown promising potential in the treatment of CRC. Specific gut microbiota can modulate the efficacy of ICIs through immune or metabolic pathways. This review summarizes recent advances in the combined application of gut microbiota and PD-1/PD-L1 inhibitors in the treatment of CRC, aiming to provide insights for expanding clinical treatment options for CRC.

This systematic review aims to comprehensively assess the epidemiology and identify risk factors associated with the severity and recurrence of hypertriglyceridemia-induced acute pancreatitis (HTG-AP). A search of PubMed, Web of Science, and Cochrane databases was conducted to identify all relevant randomized controlled trials (RCTs), prospective, or retrospective cohort studies on HTG-AP. Data related to epidemiology and risk factors for severity and recurrence of HTG-AP were extracted and analyzed. Seventy-seven studies met the inclusion criteria, comprising 1 RCT, 21 prospective studies, and 55 retrospective studies. A total of 56,617 acute pancreatitis (AP) patients were included, of which 19.99% were diagnosed with HTG-AP (n = 11,315). Compared to non-HTG-AP patients, HTG-AP patients were more likely to be male (68.7% vs. 57.3%) and younger (mean age 41.47 ± 4.32 vs. 50.25 ± 7.70 years). HTG-AP patients exhibited higher mortality rates (up to 20% vs. 15.2%), increased severity (8.3% to 100% vs. 3.8% to 47.2%), and higher recurrence rates (up to 64.8% vs. 23.3%). Analysis of temporal trends from 2002 to 2023 showed a range of HTG-AP prevalence in overall AP patients from 1.6% to 47.6%, with a slight upward trend that was not statistically significant (P = 0.1081). Regional analysis indicated relatively stable prevalence in North America (P = 0.5787), Europe (P = 0.0881), other regions (P = 0.738), while prevalence in China showed a significant increase (P = 0.0119). Thirteen studies investigated risk factors affecting HTG-AP severity, with elevated serum triglyceride (TG) levels associated with increased risk of complications such as pancreatic necrosis, systemic inflammatory response syndrome (SIRS), shock, and multi-organ failure. Additional factors including high neutrophil-to-lymphocyte ratio (NLR), elevated levels of amylase and C-reactive protein (CRP), hypocalcemia, and hypoalbuminemia were also implicated in HTG-AP severity. Smoking history, poor lipid control (TG > 3.1 mmol/L), or recurrent hypertriglyceridemia during follow-up were identified as potential predictors of HTG-AP recurrence. Our findings indicate a stable global prevalence of HTG-AP within AP patients, but a notable increase in China, possibly attributed to socio-economic and dietary factors.

Advanced gastric cancer (AGC) with unresectable factors presents a significant treatment challenge. Conventional treatments such as systemic chemotherapy, radiotherapy, and immunotherapy can delay disease progression but often yield limited outcomes. For stage III-IV gastric cancer with unresectable factors, conversion therapy based on chemotherapy can achieve tumor downstaging, providing a subset of patients with the opportunity for curative surgery. However, the efficacy of multimodal approaches combining chemotherapy, with or without immunotherapy, and conversion surgery compared to chemotherapy alone remains controversial.

The optimal clinical management of unresectable hepatocellular carcinoma (uHCC) is challenging for clinicians. Bayesian network meta-analysis was conducted to compare the efficacy and safety of different interventional strategies for uHCC.

AST-lymphocyte ratio index (ALRI) has been proposed as a potentially prognostic indicator of liver cancer patients underwent transcatheter arterial chemoembolization (TACE) in studies, but the numbers were small and the results were controversial. In this study, we systematically assessed the prognostic value of ALRI in liver cancer patients treated with TACE by integrating meta-analysis with single-center clinical analysis.

Colorectal cancer (CRC) is a high incidence cancer and health problem influenced by many factors emphasizes on the importance of identifying risk factors which can be modified. A dietary approach to stop hypertension (DASH) style promotes a balanced nutrition approach that might have effects on CRC. The aim of this study was to analyze existing evidence on the DASH diet's association with CRC.

Significant advances have occurred in the locoregional and systemic therapy landscape for hepatocellular carcinoma (HCC), with the most notable being the introduction of immune checkpoint inhibitor (ICI) combinations. ICI combinations have significantly improved the overall survival of patients with unresectable HCC, affording median survival over 2 years and long-term survival exceeding 5 years in a subset of patients. Accordingly, there has been increased interest in the earlier application of systemic therapies, including (neo)adjuvant therapy in the perioperative setting or in combination with intra-arterial therapies. However, recent data failed to demonstrate improved recurrence-free survival with use of adjuvant ICI therapy. Conversely, 2 trials showed improved progression-free survival when ICI therapies were combined with transarterial chemoembolization, although data regarding the impact on overall survival are still immature. These improved outcomes raise several new questions, including which patients with liver-localized HCC should receive systemic therapy, how should this be sequenced or combined with other available therapies, and how to manage those patients with marked responses, including consideration of liver transplantation. These questions are often determined on a case-by-case basis and best made in a multidisciplinary manner considering several factors, including tumor burden, degree of liver dysfunction, performance status, and patient's long-term goals of care.

Insulin resistance (IR) plays a noticeable role in the pathogenesis of non-alcoholic fatty liver disease (NAFLD). The triglyceride glucose-waist circumference (TyG-WC) index, a novel measure for assessing IR, may hold significant predictive value for NAFLD. However, the relationship between TyG-WC and the risk of NAFLD remains elusive. To investigate this association, this comprehensive meta-analysis was conducted.

We undertook this study to assess the efficacy of probiotics in managing adverse reactions during chemoradiotherapy in patients with colorectal cancer.

Artificial intelligence (AI) networks offer significant potential for predicting immunotherapy outcomes in gastrointestinal cancers by analyzing genetic mutation profiles. Their application in prognosis remains underexplored. This systematic review and meta-analysis aim to evaluate the effectiveness of AI-based models, which refers to systems utilizing artificial intelligence to analyze data and make predictions, in predicting immunotherapy responses in gastrointestinal cancers using genetic mutation features.