World Journal of Gastroenterology最新文献

Background: Laparoscopic distal pancreatectomy (LDP) has emerged as the preferred approach for both benign and malignant lesions located in the pancreatic body and tail. Nevertheless, a notable deficiency persists in the absence of a standardized, procedure-specific metric for evaluating and comparing surgical quality. A composite measure termed "textbook outcome (TO)", which encompasses key short-term endpoints, has been validated in laparoscopic pancreatoduodenectomy but has not yet been established in dedicated LDP cohorts. The definition and prediction of TO in this context could aid in facilitating cross-institutional benchmarking and fostering advancements in quality improvement.

Aim: To establish procedure-specific criteria for TO and identify independent predictors of TO failure in patients undergoing LDP.

Methods: Consecutive patients who underwent LDP at a single high-volume pancreatic center between January 2015 and August 2022 were retrospectively analyzed. TO was defined as the absence of clinically relevant postoperative pancreatic fistula (grade B/C), post-pancreatectomy hemorrhage (grade B/C), severe complications (Clavien-Dindo ≥ III), readmission within 30 days, and in-hospital or 30-day mortality. Multivariable logistic regression was employed to identify independent predictors of TO failure, and a nomogram was constructed and internally validated.

Results: Among 405 eligible patients, 286 (70.6%) attained TO. Multivariable analysis revealed that female sex [odds ratio (OR) = 0.62, 95% confidence interval (CI): 0.39-0.99] conferred a protective effect, while preoperative endoscopic ultrasound-guided fine-needle aspiration (OR = 2.66, 95%CI: 1.05-6.73), pancreatic portal hypertension (OR = 2.81, 95%CI: 1.06-7.45), and cystic-solid (OR = 2.51, 95%CI: 1.34-4.69) or solid lesions (OR = 1.91, 95%CI: 1.06-3.44) were independently associated with TO failure (all P < 0.05). The derived nomogram exhibited modest discrimination and calibration when assessed in both the training and validation datasets.

Conclusion: The proposed LDP-specific definition of TO is feasible and discriminative, and the developed nomogram provides an objective tool for individualized risk assessment.

The etiopathogenesis of gastrointestinal diseases is varied in nature. Various etiogenic factors described are infective, inflammatory, viral, bacterial, parasitic, dietary and lifestyle change. Rare causative agents are immunological, and others associated as idiopathic, are undiagnosed by all possible means. Some of the rare diseases are congenital in nature, passing from the parent to the child. Many of the undiagnosed diseases are now being diagnosed as genetic and the genes have been implicated as a causative agent. There is a search for newer treatments for such diseases, which is called genomic medicine. Genomic medicine is an emerging medical discipline that involves the use of genomic information about an individual. This is used both for diagnostic as well as therapeutic decisions to improve the current health domain and pave the way for policymakers for its clinical use. In the developing era of precision medicine, genomics, epigenomics, environmental exposure, and other data would be used to more accurately guide individual diagnosis and treatment. Genomic medicine is already making an impact in the fields of oncology, pharmacology, rare, infectious and many undiagnosed diseases. It is beginning to fuel new approaches in certain medical specialties. Oncology is at the leading edge of incorporating genomics, as diagnostics for genetic and genomic markers are increasingly included in cancer screening, and to guide tailored treatment strategies. Genetics and genetic medicine have been reported to play a role in gastroenterology in several ways, including genetic testing (hereditary pancreatitis and hereditary gastrointestinal cancer syndromes). Genetic testing can also help subtype diseases, such as classifying pancreatitis as idiopathic or hereditary. Gene therapy is a promising approach for treating gastrointestinal diseases that are not effectively treated by conventional pharmaceuticals and surgeries. Gene therapy strategies include gene addition, gene editing, messenger RNA therapy, and gene silencing. Understanding genetic determinants, advances in genetics, have led to a better understanding of the genetic factors that contribute to human disease. Family-member risk stratification and genetic diagnosis can help identify family members who are at risk, which can lead to preventive treatments, lifestyle recommendations, and routine follow ups. Selecting target genes helps identify the gene targets associated with each gastrointestinal disease. Common gastrointestinal diseases associated with genetic abnormalities include-inflammatory bowel disease, gastroesophageal reflux disease, non-alcoholic fatty liver disease, and irritable bowel syndrome. With advancing tools and technology, research in the search of newer and individualized treatment, genes and genetic medicines are expected to play a significant role in human health and gastroenterology.

Colorectal cancer (CRC) remains a major global health challenge, with high recurrence and mortality despite advances in surgery, chemotherapy, and immunotherapy. The study by He et al identifies a novel mechanism by which peroxiredoxin 1 (Prdx1) inhibits CRC progression through induction of pyroptosis, a pro-inflammatory form of programmed cell death. Traditionally viewed as an intracellular antioxidant that protects tumors from oxidative stress, Prdx1 assumes a paradoxical immunogenic role when released extracellularly as a damage-associated molecular pattern. Using patient samples, recombinant protein assays, and murine xenograft models, the authors demonstrate that Prdx1 activates the NOD-, LRR- and pyrin domain-containing protein 3 inflammasome/caspase-1/gasdermin D pathway, triggering membrane pore formation, tumor cell lysis, and release of interleukin-1β/interleukin-18. This cascade not only halts tumor proliferation, invasion, and migration but may also enhance anti-tumor immune surveillance. The study's strengths include rigorous mechanistic validation, clinical cohort data, inhibitor-based causal proof, and in vivo confirmation. However, questions remain regarding the upstream receptor for Prdx1, heterogeneity across CRC subtypes, and the balance between therapeutic benefit and inflammatory toxicity. By establishing Prdx1-induced pyroptosis as a driver of tumor suppression, this work advances a promising paradigm in CRC therapy, linking cell death to immune activation and pointing toward future biomarker-driven, pyroptosis-based interventions.

We read with great interest the study by Zhang et al on Yiyi Fuzi Baijiang powder (YFB), which exemplifies the power of modern methods to validate traditional Chinese medicine (TCM). The key insight is that YFB doesn't merely alter "good" or "bad" bacteria but restores the gut microbiota's holistic equilibrium. This is powerfully shown by its paradoxical reduction of anaerobic probiotics like Bifido bacterium, rectifying the diseased, hypoxic environment, causing their aberrant overgrowth. This challenges the conventional probiotic paradigm and underscores a core TCM principle: Herbal formulas treat disease by restoring the body's overall functional balance. Future research should focus on the interplay between herbal components, intestinal oxygen, and microbial metabolites to further unravel this sophisticated dialogue.

Background: The accurate prediction of lymph node metastasis (LNM) is crucial for managing locally advanced (T3/T4) colorectal cancer (CRC). However, both traditional histopathology and standard slide-level deep learning often fail to capture the sparse and diagnostically critical features of metastatic potential.

Aim: To develop and validate a case-level multiple-instance learning (MIL) framework mimicking a pathologist's comprehensive review and improve T3/T4 CRC LNM prediction.

Methods: The whole-slide images of 130 patients with T3/T4 CRC were retrospectively collected. A case-level MIL framework utilising the CONCH v1.5 and UNI2-h deep learning models was trained on features from all haematoxylin and eosin-stained primary tumour slides for each patient. These pathological features were subsequently integrated with clinical data, and model performance was evaluated using the area under the curve (AUC).

Results: The case-level framework demonstrated superior LNM prediction over slide-level training, with the CONCH v1.5 model achieving a mean AUC (± SD) of 0.899 ± 0.033 vs 0.814 ± 0.083, respectively. Integrating pathology features with clinical data further enhanced performance, yielding a top model with a mean AUC of 0.904 ± 0.047, in sharp contrast to a clinical-only model (mean AUC 0.584 ± 0.084). Crucially, a pathologist's review confirmed that the model-identified high-attention regions correspond to known high-risk histopathological features.

Conclusion: A case-level MIL framework provides a superior approach for predicting LNM in advanced CRC. This method shows promise for risk stratification and therapy decisions, requiring further validation.

Background: Post-endoscopic retrograde cholangiopancreatography pancreatitis (PEP) is a prevalent and potentially serious complication in patients undergoing endoscopic retrograde cholangiopancreatography.

Aim: To comprehensively assess the efficacy of indomethacin therapy in reducing PEP risk.

Methods: We searched PubMed, EMBASE, Scopus, and Cochrane Library databases to identify randomized controlled trials (RCTs) that compared rectal indomethacin with a control group to prevent PEP. Duplicates were removed, and studies were included based on the established inclusion criteria. We used the Cochrane Collaboration's tool to assess the risk of bias in the RCTs. A random-effects model was applied to produce pooled risk ratios (RRs) with 95% confidence intervals (CIs).

Results: We included a total of 30 RCTs involving 16977 patients. Compared to the control group, rectal indomethacin showed comparable rates of overall PEP (PEP; RR = 0.85, 95%CI: 0.69-1.04, I ² = 79%) with no statistically significant difference of RR in mild (RR = 0.92, 95%CI: 0.74-1.14), moderate (RR = 0.78, 95%CI: 0.59-1.02), or severe PEP (RR = 1.12, 95%CI: 0.75-1.67). There was also no difference in cases of adverse events (RR = 0.97, 95%CI: 0.69-1.35), abdominal pain (RR = 1.14, 95%CI: 0.80-1.62), bleeding (RR = 1.07, 95%CI: 0.70-1.63), or mortality (RR = 0.86, 95%CI: 0.56-1.33) between the two groups. Subgroup analyses were also performed.

Conclusion: Rectal indomethacin appears to be safe and may offer benefit in selected high-risk patients, though findings should be interpreted with caution due to high heterogeneity.

Background: Chronic hepatitis B virus (HBV) infection acquired in childhood frequently presents with mild or nonspecific symptoms, yet a distinct subset of pediatric patients develops rapid progression to liver cirrhosis (LC) before adulthood.

Aim: To identify clinical and pathological characteristics of pediatric HBV-related LC.

Methods: A total of 1332 pediatric patients with chronic HBV infection from the Fifth Medical Center of PLA General Hospital from January 2010 to January 2023 were included in this study. We identified 62 pediatric HBV-related LC by liver biopsy from the group. Subsequently, we described the clinical and pathological characteristics of pediatric LC. And 64 pediatric chronic hepatitis B (CHB; age and sex were matched with pediatric LC group) and 69 adult HBV-related LC (sex were matched with pediatric LC group) were enrolled to further demonstrate clinical and pathological differences between pediatric LC, pediatric CHB and adult LC.

Results: We enrolled 62 pediatric LC, including 54 (87.1%) males and 8 (12.9%) females. The median age was 11 (4-14) years old. The pediatric LC group showed significantly lower median quantitative HBV DNA loads (log₁₀IU/mL: 6.3 vs 17.4, P < 0.001), reduced HBsAg titers (log₁₀IU/mL: 3.11 vs 8.956, P < 0.0001), and diminished hepatitis B e antigen-positive positive rate (81.4% vs 93.8%, P < 0.05) compared with pediatric CHB. A higher proportion of pediatric patients were asymptomatic (77.4%) compared to adult patients (11.6%) as they first diagnosed as LC, pediatric LC showed milder initial symptoms compared with adult patients such as fatigue (4.8% vs 27.5%), abdominal discomfort (9.7% vs 23.2%), nausea (0% vs 10.1%), and poor appetite (6.5% vs 8.7%; all P < 0.0001). Notably, pediatric LC can achieve a significant percentage of functional cure compared with adult LC as 17.4% and 0%. The incidence of progression of LC in children after antiviral therapy continues to be much lower than that in adult LC (hazard ratio = 6.102, 95% confidence interval: 1.72-21.65, P = 0.00051). While the incidence of LC remission in children after antiviral therapy continues to be much higher than that in adult LC (hazard ratio = 0.055, 95% confidence interval: 0.07128-0.2802, P < 0.0001).

Conclusion: Pediatric patients with HBV-related cirrhosis exhibit elevated virological parameters and heightened transaminase levels than adult patients. However, the frequent paucity of overt clinical symptoms contributes to diagnostic challenges. Notably, early initiation of antiviral therapy in this population substantially improved clinical outcomes.

Background: The gut microbiota displays pronounced compositional differences between pediatric and adult populations, both under normal conditions and during the development of inflammatory bowel disease (IBD). These structural variations are accompanied by substantial changes in microbial metabolic activity.

Aim: To identify novel early diagnostic biomarkers of IBD, we performed an integrated multi-omics analysis that included assessing microbial community structure and profiling microbial metabolic activity in pediatric and adult cohorts with ulcerative colitis (UC) and Crohn's disease (CD).

Methods: The study cohort consisted of two distinct age groups with confirmed IBD diagnoses: Adult patients (aged 45 to 70) and pediatric patients (aged 5 to 15), each diagnosed with either CD or UC. 16S rRNA gene sequencing was performed using the MinION™ Mk1B platform, with data acquisition carried out via MinKNOW software version 22.12.7 (Oxford Nanopore Technologies). Stool samples were analyzed using a Shimadzu QP2010 Ultra GC/MS system equipped with a Shimadzu HS-20 headspace extractor.

Results: Comparative analysis revealed significant age-related differences in the abundance of Bacteroidota, with pediatric IBD patients showing a lower prevalence compared to adults. Microbial profiling identified Streptococcus salivarius and Escherichia coli as potential biomarkers for assessing IBD risk in children. Furthermore, metagenomic analysis uncovered five microbial signatures with diagnostic potential for CD: Ralstonia insidiosa, Stenotrophomonas maltophilia, Erysipelatoclostridium ramosum, Blautia spp., and Coprococcus comes. Using comprehensive metabolomic profiling, we developed and validated novel risk prediction algorithms for pediatric IBD. The CD risk stratification model identifies high-risk patients based on two key biomarkers: An elevated IBD risk coefficient score and reduced levels of 1H-indole-3-methyl. The UC risk prediction model incorporates three metabolic biomarkers indicative of increased disease risk: An elevated risk coefficient score, increased acetate levels, decreased pentanoic acid, and altered excretion of p-cresol (4-methylphenol).

Conclusion: Functional metabolomics holds transformative potential for IBD diagnostics across all age groups, with especially significant implications for pediatric patients. The distinct metabolic and metagenetic profiles observed in the pediatric cohort may represent primary alterations in IBD, providing valuable insights for exploring novel mechanisms underlying disease pathogenesis.

Preventing the recurrence of lung oligometastases after local therapy in patients with colorectal cancer is an area requiring investigation. A recent article demonstrated that adding capecitabine maintenance therapy after radiofrequency ablation improved the 5-year overall survival (88.7% vs 69.1%) and reduced local tumor progression (22.7% vs 49.0%) compared with radiofrequency ablation alone. Although progression-free survival did not differ significantly between the two treatments, multivariate analysis confirmed a robust survival benefit. These findings support the use of systemic maintenance to eradicate micrometastases after locoregional control and warrant validation in prospective randomized trials.

Background: Although the triple therapy of transarterial chemoembolization (TACE) combined with immune checkpoint inhibitors and tyrosine kinase inhibitors is becoming an effective treatment for unresectable hepatocellular carcinoma (uHCC). However, there is still a lack of effective tools for predicting therapeutic effects at present.

Aim: To develop a predictive tool for the prognosis of uHCC patients treated with TACE, sintilimab and lenvatinib.

Methods: Based on multicenter data, this study constructed and validated an AADN score as variables to predict overall survival in patients treated with this combination therapy. This study included 188 uHCC cases (training cohort: n = 101, validation cohort: n = 87) from three different hospitals. Who were treated with TACE, sintilimab and lenvatinib.

Results: In multivariate analysis, alpha-fetoprotein ≥ 100 ng/mL [hazard ratio (HR) = 2.579, P = 0.010], alkaline phosphatase > 120 U/L, (HR = 2.234, P = 0.021), direct bilirubin > 7.3 μmol/L (HR = 2.931, P = 0.007) and neutrophil to lymphocyte ratio > 2.5 (HR = 3.127, P = 0.006) were identified as independent prognostic factors and were used to establish the AADN score. Kaplan-Meier survival curves and time-dependent receiver operating characteristic curves were used to assess the accuracy of the AADN score, with area under receiver operating characteristic curve values of 0.827 (training cohort, 95% confidence interval: 0.743-0.911) and 0.832 (validation cohort, 95% confidence interval: 0.742-0.923). According to the score, the patients were divided into low-risk, intermediate-risk and high-risk groups. Overall survival and progression-free survival were significantly different between groups.

Conclusion: The AADN score can distinguish the prognostic risk of uHCC patients treated with TACE, sintilimab and lenvatinib, provides a basis for individualized treatment decision-making, and have clinical application prospect.