Employment disruption and missed workdays after neoadjuvant therapy receipt for high-risk gastrointestinal cancer.

Gastrointestinal (GI) cancer remains a leading cause of cancer-related mortality worldwide, with epigenetic alterations progressively recognized as key drivers of tumorigenesis and therapeutic resistance. Through its role in facilitating cell proliferation, inhibiting apoptosis, driving epithelial-mesenchymal transition (EMT) and metastasis, reinforcing angiogenesis, inducing metabolic reprogramming, mediating chemoradiotherapy resistance and maintaining cancer stem cell (CSC) properties, protein arginine methyltransferase 5 (PRMT5) has emerged as a key oncogenic regulator among these epigenetic modifiers implicated in GI cancer progression. Elevated PRMT5 expression has been observed in multiple GI cancer subtypes, comprising gastric cancer (GC), colorectal cancer (CRC), hepatocellular carcinoma (HCC) and pancreatic cancer, where PRMT5 markedly contributes to tumorigenesis via symmetric dimethylation of histone (e.g., dimethylation of histone H4 at arginine 3) and non-histone substrates [e.g., AKT1 and sterol regulatory element-binding protein 1a (SREBP1a)]. In GC, PRMT5 activates the PI3K/AKT pathway [e.g., by methylating AKT1 at arginine (R)391 and upregulating c-Myc], facilitating tumor cell proliferation and survival. In CRC, PRMT5-mediated methylation of SMAD4 (e.g., at R361) reinforces TGF-β signaling, facilitating EMT and metastasis, while its interaction with EGFR further amplifies proliferative signals. PRMT5 also upregulates VEGF expression (e.g., via chromatin remodeling at its promoter), stimulating angiogenesis and inhibits ferroptosis (e.g., by suppressing the solute carrier family 7 member 11/glutathione peroxidase 4 axis in HCC), supporting tumor survival. Furthermore, PRMT5 markedly contributes to metabolic reprogramming (e.g., accelerating de novo lipogenesis via SREBP1a methylation and glycolysis via epigenetic silencing of F-box and WD repeat domain-containing protein 7), while strengthening DNA repair (e.g., homologous recombination) and CSC self-renewal (e.g., via the β-catenin/IL-8 axis in CRC) to confer therapy resistance. However, PRMT5 inhibitors (e.g., GSK3326595 and JNJ-64619178) demonstrate antitumor effects in preclinical models and methylthioadenosine phosphorylase (MTAP) deletion may serve as a potential biomarker for patient selection. The clinical translation of PRMT5 inhibitors is limited by hematological toxicity, lack of robust predictive biomarkers beyond MTAP and potential resistance from compensatory PRMT family members. It is key to clarify GI cancer-specific PRMT5 mechanisms and potentially develop optimized combination therapies in the future.

Gastrointestinal (GI) tumors, characterized by high incidence and mortality rates, represent a major global health challenge. Metabolic reprogramming has been recognized as one of their defining hallmarks. Beyond aberrant glucose metabolism, accumulating evidence has revealed how dysregulated fatty acid (FA) metabolism plays a multifaceted role in regulating the tumor microenvironment (TME). By modulating tumor, immune, and stromal cells, FA metabolism profoundly influences tumorigenesis, progression, and cell death. Despite advances in current treatments, the inherent immunosuppressive nature of TME and the therapeutic resistance of tumor cells still remain major obstacles. Notably, targeting key nodes of FA metabolism has emerged as a promising strategy to overcome these challenges. Thus, in this review, we systematically delineate how FA metabolic reprogramming shapes the GI tumor microenvironment by regulating tumor, immune, and stromal cells in multiple ways. Furthermore, we critically explore the translational potential of FA metabolism in biomarker development, targeted therapy, and combination therapeutic strategies. By synthesizing these insights, this review aims to provide forward-looking perspectives on future therapeutic strategies against GI tumors.

Gastrointestinal tumors are common malignant tumors of the digestive system, which globally threaten human health. Notably, it has been discovered that blood and other circulating body fluids are not completely sterile; instead, they harbor complex and dynamic microbial DNA and signatures [circulating microorganisms (CM)]. These microorganisms primarily originate from the microbial translocation (including bacterial fragments, DNA and metabolites) through a compromised intestinal barrier, and are closely associated with the initiation and progression of gastrointestinal tumors, thus providing novel perspectives for early tumor diagnosis and prognosis. Although there is currently no evidence that CM can directly cause cancer, their metabolites and exosomes may contribute to tumor microenvironment remodeling. On one hand, they activate pattern recognition and inflammatory signaling pathways, such as Toll-like receptor/signal transducer and activator of transcription, potentially inducing and maintaining low-grade chronic inflammation. On the other hand, they may facilitate immune evasion, potentially promoting the 'inflammation-cancer' transition. With the development of metagenomic technologies and the maturation of next-generation high-throughput sequencing technologies, CM have shown potential as liquid biopsy biomarkers for the early diagnosis of gastrointestinal tumors. Interventions targeting specific CMs have also shown prospects for enhancing efficacy in early clinical trials. However, the field still faces numerous challenges, including insufficient depth of mechanistic validation and a lack of standardized detection protocols. Future efforts should aim to conduct further systematic research to clarify the biological functions and clinical translational value of CM in gastrointestinal tumors.

To identify factors and preexisting conditions that are associated with overall cancer mortality, lung cancer mortality, and gastrointestinal cancer mortality in patients after acute myocardial infarction (AMI). In total 10,718 AMI patients aged 25 to 74years were evaluated. All cases of AMI that occurred in the study region of the population-based Myocardial Infarction Registry Augsburg during the period from 2000 to 2017 were analyzed. Median follow-up time was 6.6years (IQR 2.8-11.2). Multivariable Cox regression models were calculated for overall cancer mortality (ICD-10: C00-D48), lung cancer mortality (C34), and gastrointestinal cancer mortality (C15-C25). During the study period, 633 patients died from cancer, including 155 deaths from lung cancer and 212 deaths from gastrointestinal cancer. Higher age, current smoking and diabetes were associated with an increased cancer mortality risk in patients after AMI, whereas female sex, never smoking and platelet aggregation inhibitor intake were inversely related to overall cancer mortality. Higher lung cancer mortality in patients after AMI was linked with advanced age and current smoking. For gastrointestinal cancer death in patients after AMI age, diabetes and current smoking were associated with higher risk, whereas female sex, never smoking, platelet aggregation inhibitor and statin intake were inversely associated. Factors already known for preventing cardiovascular disease were inversely associated with cancer mortality after AMI. These findings support the importance of comprehensive patient education regarding a healthy lifestyle following AMI. Overall, physicians targeting secondary prevention after AMI can also highlight the positive effects of these measures on cancer mortality.

The role of claudins in the physiology and pathology of the digestive system.

ASO Visual Abstract: Double Jeopardy: Risks of Opioid-Benzodiazepine Co-prescription in Older Adults with Gastrointestinal Cancer.

Artificial intelligence in gastrointestinal cancers: From early detection to precision therapy

Gastrointestinal cancers rank among the most common malignancies globally, and although surgical resection remains the cornerstone of curative therapy, it is associated with considerable postoperative morbidity and mortality. Emerging evidence suggests that the gut microbiome is a critical determinant in the pathogenesis of postoperative complications, including surgical site infections, anastomotic leakage, and postoperative ileus. Microbiome-targeted interventions - including probiotics, prebiotics, and synbiotics - have shown promise in modulating microbial communities and supporting postoperative recovery; however, clinical efficacy remains inconsistent, and standardized perioperative protocols are yet to be established. This review summarizes current evidence on the interactions between gastrointestinal cancer surgery and the perioperative gut microbiome, emphasizing opportunities to harness microbiome-targeted interventions to reduce complications and enhance recovery.

Glucagon-like peptide-1 receptor agonists (GLP-1RAs) are increasingly prescribed for type 2 diabetes and obesity, conditions frequently encountered in gastroenterological practice. Their pleiotropic effects along the gut-pancreas-liver axis have raised both therapeutic interest and safety concerns, particularly regarding hepatic outcomes, gastrointestinal cancers, peri-endoscopic management, and gastrointestinal adverse events. This position paper, endorsed by the Italian Society of Gastroenterology (SIGE), was developed according to the GRADE framework and provides evidence-based recommendations for the safe and effective management of GLP-1RAs in gastroenterology, highlighting their favorable benefit-risk profile while identifying key knowledge gaps requiring future prospective studies. GLP-1RAs may be safely used in patients with diabetes or obesity and metabolic dysfunction-associated steatotic liver disease. In cirrhotic patients with diabetes or obesity, GLP-1RAs appear safe and are associated with reduced hepatic decompensation. Available evidence does not support an increased risk of esophageal, gastric, colorectal, or pancreatic cancer, while a potential reduction in hepatocellular carcinoma incidence is suggested. Routine discontinuation of GLP-1RAs before upper gastrointestinal endoscopy is not recommended. GLP-1RAs increase the risk of mild, transient gastrointestinal adverse events and cholelithiasis but are not associated with severe gastrointestinal complications or acute pancreatitis.

Artificial intelligence (AI) has the potential of reshaping GI oncology by enabling more nuanced interpretation of complex clinical, imaging, and molecular data, while supporting more timely and patient-centered decisions. This article synthesizes perspectives across the GI cancer continuum, beginning with a framework for context-aware AI that emphasizes metadata, multimodal integration, and lifecycle quality and safety as foundations for trustworthy tools that clarify, rather than conceal, uncertainty. Next, AI in endoscopy is highlighted as an example in clinic practice, focusing on computer-aided detection and diagnosis systems that not only increase adenoma detection rates but also raise questions about surveillance burden, real-world effectiveness, and the balance between skill enhancement and potential deskilling of endoscopists. Another section explores how AI can help GI oncologists design, prioritize, and implement highly innovative clinical trials-particularly multi-omic and imaging-driven approaches-while envisioning a future in which far more patients participate in trials that align with their goals and values. The final section reviews emerging AI-enabled clinical trial matching pipelines, including large language model-based retrieval and prescreening tools that operate on real-world electronic health record and protocol data, and discusses challenges related to bias, privacy, explainability, and workflow integration. Together, these contributions argue that the greatest impact of AI in GI oncology will come from deliberately aligning technical capabilities with highly relevant patient-centered clinical questions, ethical governance, and implementation strategies that expand access to trials and improve outcomes for patients with GI malignancies.

Cardiovascular-kidney-metabolic syndrome stages and risk of diverse gastrointestinal diseases: a prospective cohort study and integrative proteomic analysis.

The Krüppel-like family (KLF) are important transcriptional regulators that have important, context-specific roles in gastrointestinal (GI) malignancies. Their roles are very heterogeneous; each of the KLF members may play tumor-suppressive or tumor-promoting roles, depending on the type of tumor, clinical stage and the cellular microenvironment, which fine-tunes the core biological processes of tumor cell proliferation, apoptosis, epithelial-mesenchymal transition and metabolism. This is a context-dependent functional heterogeneity that poses a big challenge in the translation of KLF family transcription factors from basic research into clinical applications. In addition to these classical regulatory functions, KLFs have a key role in the restructuring of the tumor immune microenvironment (TIME). KLFs have the potential to affect the effectiveness of cancer immunotherapy by modulating immune cell infiltration, immune cell functions and immune evasion by tumors. The present review is a systematic review that summarizes the molecular regulatory mechanisms of KLFs in the major GI malignancies, such as colorectal, gastric, liver, esophageal and pancreatic cancer. The present review points to their control of major signaling pathways, including Wnt/β-catenin and PI3K/AKT, and their new roles in the remodeling of TIME. Moreover, the present review assesses their translational utility as diagnostic and prognostic biomarkers and therapeutic targets, and confronts the clinical issues involved in targeting transcription factors, thus giving a theoretical basis for oncology approaches in different types of GI cancer.

Irreversible electroporation (IRE) is a minimally invasive, non-thermal, and cell-selective technique. When combined with the noninvasive nature of contact electrodes, they hold great promise for the treatment of cardiac conditions, gastrointestinal tumors, and superficial lesions. However, its broader clinical application is hindered by its reliance on a kilovolt-level, high-voltage pulse characteristics power supply and the lack of real-time postoperative assessment methods for evaluating ablation efficacy. To address these challenges, a contact electrode system with integrated IRE and impedance monitoring functions was developed. Numerical simulations were performed to optimize the anode, gap, and cathode widths in the concentric electrode design. This ensured efficient electric-field focusing under low-voltage conditions. The ablation performance was verified using a potato model. A four-electrode impedance measurement technique was used to capture the spectral characteristics of biological tissues. The impedance changes were analyzed using a double-shell equivalent circuit model. The system achieved a 2mm ablation depth at 125 V, which is suitable for the treatment of superficial lesions. This reduces the required voltage from the kilovolt level to the hundred-volt level. The four-electrode method reduced contact resistance interference, and the Nyquist plots showed a unique double-arc pattern. Changes in cell wall resistance correlated with ablation depth ( = 0.86) with a prediction error of <10%. This study presents an innovative approach for IRE therapy that combines low-voltage operation with real-time feedback through impedance spectroscopy, thereby offering improved safety and treatment monitoring.

Although the prognostic significance of low muscle mass has been established in cancer outcomes, standardizing cutoff values remains challenging. Various criteria based on the skeletal muscle index (SMI) have been proposed. The Z-score derived from the body-size-adjusted skeletal muscle area (SMA) has been proposed (Derstine's Z-score), which offers the potential for unbiased assessments across diverse body sizes. However, large-scale cohort validation of clinical outcomes using this approach has not been conducted. This study aimed to validate Derstine's Z-score in a different race than the original paper. This single-center study included 2869 patients with gastrointestinal or genitourinary cancers who underwent radical surgery. The SMA on computed tomography at the third lumbar level was used to calculate Derstine's Z-scores by normalizing the ratio of the SMA to height- or height-squared with the body size-adjusted mean and sex-specific standard deviation. We employed Z-score cutoffs of -2 and -3, the nearest whole number to the optimal cutoff, calculated using maximally selected rank statistics with several p-value approximations. The effects of Derstine's Z-scores on cancer-specific survival (CSS) and overall survival (OS) were calculated and compared with the previously proposed SMI definition. Kaplan-Meier analysis demonstrated significant discrimination of CSS and OS based on Derstine's Z-scores. A -3 cutoff for Derstine's Z-score, rather than the conventional -2, achieved the highest hazard ratio, with values of 1.61 for CSS and 1.94 for OS. Multivariate analysis revealed that low muscle mass, as defined by Derstine's Z-scores, was associated with poor prognosis, with hazard ratios of 1.42 for CSS and 1.62 for OS, enhancing the predictive capability of survival models comparable to the SMI definition. The Derstine Z-score is a valuable prognostic indicator in patients with cancer. A cutoff value of -3 may better capture low muscle mass in a different race than the original paper.

The dual role of formyl peptide receptor 1 (FPR1) in gastrointestinal inflammation and carcinogenesis: mechanisms and therapeutic implications.

This article provides an overview of changes of the incidence, stage distribution, and survival of gastrointestinal stromal tumors (GIST) in Germany between 2003 and 2021. Data on the incidence, TNM categories, UICC stage, and survival with respect to GIST in Germany were obtained from the national Centre for Cancer Registry data at the Robert Koch-Institute (Berlin, Germany). The age-standardized incidence was 1.6 (men) and 1.4 (women) per 100,000 for the 2021 diagnosis year and has increased approximately threefold in the years since 2003. The most commonly reported GIST UICC stage in 2020 was stage I (men: 53%, women: 39%). The proportion of small tumours (TNM-T category 1) has increased between 2010 and 2020. The 5-year relative survival rate for individuals with GIST improved from 74% to 82% (men) and from 80% to 88% (women) between the 2003-2008 and 2014-2021 time periods, respectively. In line with national and international data, the incidence of GIST in Germany increased between 2003 and 2021, while survival has improved in the same time period after the introduction of imatinib for adjuvant treatment of GIST in Germany in the year 2009. An increasing number of small endoscopically detected lesions may have contributed to the rising incidence of GIST. Primary care physicians should be aware of the increasing frequency of GIST. With the collection of detailed therapy data and information on prognostic markers, further evaluations of clinical issues will also be possible in the future using German cancer registry data.

The role of socioeconomic position in use of systemic anticancer therapy.

ASO Visual Abstract: Patient-Reported Symptom Recovery After Upper Gastrointestinal Cancer Surgery: A Prospective Study Using the MDASI-UGI-Surg.

Acute postoperative pain remains prevalent among patients undergoing gastrointestinal tumor surgery. The study was conducted to evaluate the efficacy of transcutaneous auricular vagus nerve stimulation (taVNS) in alleviating postoperative pain in this population. This patient- and assessor-blinded randomized controlled trial was conducted at the Second Affiliated Hospital of Zhejiang University School of Medicine. Eligible participants who underwent elective laparoscopic gastrointestinal tumor surgery were randomly assigned to the taVNS or control stimulation group. Both groups received the stimulation on the day before surgery and the day after surgery. The primary outcome was the change in visual analogue scale (VAS) scores at 24h postoperatively. The median reduction in VAS scores was 12.0 in the taVNS group, compared with 5.0 in the control stimulation group (median [interquartile range, IQR] 12.0 [10.0-13.3] mm vs 5.0 [2.0-8.0] mm; P < 0.001). Additionally, the taVNS group showed lower cumulative morphine milligram equivalents (MME) at 48h (median [IQR] 0 [0-5] mg vs 5 [0-10] mg; P=0.004) and 72h (median [IQR] 0 [0-5] mg vs 5 [0-10] mg; P=0.002), and shorter time to first flatus (median [IQR] 45 [40-60]h vs 75 [60-85]h; P < 0.001). The incidence of complications, length of hospital stay, and quality of recovery-15 (QoR-15) scores are similar between groups. TaVNS statistically alleviated postoperative pain in patients undergoing gastrointestinal tumor surgery, decreased analgesic requirements, and promoted gastrointestinal function recovery. NCT06763913.