Juvenile spondyloarthritis (JSpA) shares genetic, immunopathogenic, and environmental features with pediatric inflammatory bowel disease (IBD), placing patients at an elevated risk for IBD. We aimed to evaluate the prevalence of IBD and identify potential early markers for its recognition in children with JSpA, trying to improve its diagnostic, screening, and treatment strategies. Children diagnosed with JSpA were prospectively evaluated. Fecal calprotectin (FCP) was measured in all participants, and those with elevated FCP (> 100 μg/g) or two or more IBD-related symptoms (chronic diarrhea, weight loss/growth retardation, abdominal pain, or bloody/mucous stool) underwent ileocolonoscopy with histopathological and radiological assessment. Altogether 81 children (71.6% male) with a mean age of 194 months at adimission were included, and 23 underwent endoscopic evaluation (19 for elevated FCP, 4 for two or more IBD-related symptoms). Among them, 10 (43.5%) had both macroscopic and microscopic presentation of colitis, 4 (17.4%) had microscopic appearance only, and 9 (39.1%) had normal histopathological findings. Notably, 94.7% of children with elevated FCP levels were asymptomatic for IBD. Among FCP-positive patients, 13 (68.4%) showed macroscopic and/or microscopic mucosal changes. Overall, colitis was confirmed in 14 (17.3%) patients. Sacroiliitis, as confirmed by magnetic resonance imaging, was significantly more frequent among both FCP-positive and colitis-positive patients ( p < 0.001 and p = 0.008, respectively). No significant associations were found between FCP levels or intestinal inflammation and disease activity, acute-phase reactants, or treatment status. IBD and subclinical colitis are relatively frequent in JSpA. Elevated FCP represents a promising noninvasive biomarker for detecting silent intestinal inflammation, warranting confirmation by ileocolonoscopy.
We aimed to explore the global burden and trends of early-onset gastrointestinal (GI) cancers, defined as those diagnosed in individuals younger than 50 years of age, from 1990 to 2021 based on the Global Burden of Disease Study 2021 (GBD 2021). Data of disability-adjusted life-years (DALYs), incidence, and corresponding age-standardized rates were extracted to assess the burden and trends of early-onset GI cancers, including esophageal, gastric, liver, colorectal, pancreatic, and gallbladder and biliary tract cancers from 1990 to 2021. Colorectal cancer had the highest age-standardized DALYs rate (ASDR) and incidence rate (ASIR) globally at 101.37 and 5.37 per 100 000 in 2021. Moreover, it showed the greatest ASIR growth over the past three decades, with projections indicating it would remain the leading cause by 2040. Colorectal, gastric, and liver cancers ranked the top three contributors to disease burden in 2021, with gastric cancer showing the most significant decline (average annual percentage change [AAPC] for ASDR: −2.27; for ASIR: −1.71). Elevated body mass index was the risk factor for most of these cancers, with AAPC ranging from 0.68 to 5.09. Additionally, early-onset pancreatic cancer had the greatest impact in Eastern Europe, while gallbladder and biliary tract cancer was more prevalent in Southern Latin America. East Asia had the heaviest burden of other cancers. Early-onset colorectal, gastric, and liver cancers were the top three contributors to disease burden in 2021. Preventing these cancers and reducing obesity should be the main priorities for public health.
To discuss less well-defined indications for percutaneous cholangioscopy (PC) that have been described in case reports and other studies. The role of PC is expanding in the treatment of biliary and pancreatic pathologies and presents unique advantages and drawbacks when compared to other endovascular diagnostic and therapeutic modalities. The utility of cholangioscopy in the treatment of choledocholithiasis has been well defined, and therefore here we focus on other indications. A thematic review was conducted by searching PubMed for studies reporting indications for PC since January 1, 2000. Relevant data were extracted, synthesized, and analyzed to identify trends and gaps in the use of this procedure. Indications for PC include indeterminate biliary strictures, tumor evaluation and staging, primary sclerosing cholangitis (PSC), hemobilia, foreign object retrieval, and pancreatic pathologies, and so on. PC is generally used when other techniques such as endoscopic retrograde cholangiopancreatography (ERCP) or magnetic resonance cholangiopancreatography (MRCP) are insufficient or contraindicated. Reasons for this include technical complexity, anatomic abnormalities, and cost. PC has similar rates of complication as other biliary techniques such as ERCP, albeit marginally higher rates of cholangitis, which can be successfully mitigated with antibiotics. PC enables direct visual inspection of the biliary tree with correlative cholangiography to better appreciate and manage biliary pathology not amenable to peroral cholangioscopy, ERCP, or MRCP.
Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease that inevitably leads to swallowing difficulties as the disease progresses. Percutaneous endoscopic gastrostomy (PEG) is recommended for optimal supportive management of dysphagia among these patients. We aimed to investigate PEG-related complications and risk factors in patients with ALS. Medical records of the ALS patients who underwent PEG from March 2006 to February 2025 in a single tertiary care center were retrospectively reviewed. PEG-related complications and risk factors were assessed through chart review, endoscopic reports and images, radiological findings, and follow-up data. Altogether 501 ALS patients (262 men) underwent PEG, of whom 60 developed early complications and 82 developed late complications, including 11 patients who developed both. Pneumoperitoneum was more common in underweight patients ( p = 0.004), and wound infection was more common in patients with pre-PEG ileus ( p = 0.044). Multivariate analysis revealed that low albumin level, long procedure time, and ileus were significantly associated with early complications. Obesity and ileus were independent risk factors for buried bumper syndrome. Those with an internal bolster at the upper body of the stomach and with an external bolster in the midline of the abdomen were at significant risk of inadvertent PEG removal. Albumin and body mass index extremes are predictors of complications, and care is needed when PEG is performed on patients with pre-PEG ileus. To reduce such risks, the PEG tube should not be inserted into the upper body of the stomach or the midline of the abdomen.
Endoscopic submucosal dissection (ESD) is the preferred treatment for early gastric cancer and gastric adenomas. However, ESD-induced artificial ulcers leads to pain, bleeding, and delayed healing. In recent years, advances have been made for the treatment of post-ESD ulcers. Currently available treatment options for post-ESD ulcers include proton pump inhibitors and potassium-competitive acid blockers, mucosal protective agents such as rebamimide, and novel biomaterials such as fibrin glue and hydrogel-based products. In addition, advanced imaging technologies such as Doppler probe ultrasound and infrared imaging systems have been adopted to assist in the detection of invisible vessels. These novel approaches have shown promising efficacies in promoting ulcer healing and reducing post-procedure adverse events. Here we review the factors that might influence ulcer healing after ESD and the recent advances in the management of ESD-induced iatrogenic gastric ulcers. Further investigation is warranted regarding their long-term safety, cost-effectiveness, and individualized treatment strategies.
Primary liver cancer (PLC) is a leading cause of global cancer-related mortality, with rising incidence and survival disparities. We aimed to analyze its long-term survival trends that likely help establish future prevention and treatment strategies for PLC. Using the Surveillance, Epidemiology, and End Results (SEER) Program (1975–2019), we assessed long-term survival rates of PLC patients stratified by age groups, sex, race, and SEER tumor stage using period analysis. Model-based period analysis was employed to predict the 5-year relative survival rates (RSRs) during 2020–2024. Survival statistics included observed survival rates (OSRs), RSR, conditional RSR (CRSR), and age-standardized RSR (ARSR). From 2015 to 2019, female patients with PLC had a higher 5-year ARSR of 27.26% compared to male patients (24.81%). The 5-year CRSR improved to 72.17% in women and 70.05% in men. The 5-year RSR declined with age and from localized tumor stage (41.45%) to distant cancer (5.52%) in men. In addition, black male patients had the lowest 5-year ARSR (19.61% vs. 23.86% in white males and 31.22% in men of other races). Long-term trends during 1975–2019 showed rising survival rates, yet disparities persisted. Projections for 2020–2024 estimated an overall 5-year RSR of approximately 30%, with persistent gaps for patients aged ≥ 75 years and black males. Despite improved PLC survival over the 45 years, persistent disparities in age, sex, race, and tumor stage underscore the need for early detection and equitable care. The converging prognosis among long-term survivors highlights the value of survivorship programs.
Low baseline viremia and an early treatment response predict the best outcomes in hepatitis B virus (HBV)-infected patients treated with nucleoside analogues with low barriers to resistance. The aim of this study was to assess the long-term results and effectiveness of lamivudine in patients with low baseline viremia and early virological treatment response. In this multicenter, real-life setting study, 111 antiviral-naive patients with low baseline viremia (HBV DNA <10 7 copies/mL) plus an early virological response (HBV DNA <300 copies/mL at week 24) treated with lamivudine were enrolled. The primary end-point was treatment failure, defined as the re-emergence of detectable viremia or at least a 1 log increase in HBV DNA, resulting in a titer of ≥300 copies/mL with lamivudine treatment after week 24, which required treatment modification. Altogether 111 patients, including 78 non-cirrhotic and 33 cirrhotic patients, were included in the study. Treatment failure occurred in 30.8% of the non-cirrhotic patients over a median follow-up period of 32.5 months, and the 1-, 2-, 3-, 4- and 5-year treatment failure rates were 6.5%, 14.0%, 31.4%, 39.6% and 43.1%, respectively. Treatment failure occurred in 28.8% of the whole group. There were no differences between the cirrhotic and non-cirrhotic patients. Lamivudine treatment had a high treatment modification rate in patients with low baseline viremia and early virological response over a long-term follow-up in a real-life setting. The pretreatment and on-treatment favorable characteristics found in the studies with telbivudine appeared to be inapplicable to lamivudine.
In this retrospective study we aimed to assess the diagnostic, monitoring, and prognostic utility of transabdominal ultrasound (TBUS) in patients with Crohn's disease in China and evaluate the utility of 16-week bowel wall thickness (BWT) reduction as a predictor of long-term outcomes. Patients with CD, either newly or previously diagnosed, who received biologic therapy for the first time and underwent baseline TBUS and endoscopy between June 2022 and September 2023 were included, with follow-up TBUS performed at Weeks 16 and 52 after the initiation of biologic therapy; clinical, ultrasound, laboratory, and disease activity data were collected. Among the 60 patients, TBUS identified bowel wall thickening in 55 patients, with an average thickness of 7.36 ± 2.56 mm. The Limberg score of vascularization in the affected segments was ≥ 3 in 58.3% of the patients. Ascites, lymphadenopathy, and mesenteric fat hypertrophy were observed in 23.3%, 41.7%, and 41.7% of the patients, respectively. Significant correlations were found between baseline SES-CD or CDAI and BWT ( r = 0.650 for SES-CD and 0.331 for CDAI) and the Limberg score ( r = 0.538 for SES-CD and 0.387 for CDAI). The receiver operating characteristic (ROC) curve analysis revealed high diagnostic accuracy for BWT (area under the ROC curve [AUROC] 0.973) and the Limberg score (AUROC 0.927). Follow-up TBUS at Weeks 16 and 52 showed significant reductions in BWT and Limberg score. BWT reduction at Week 16 was significantly associated with CD clinical remission at Week 52 ( p < 0.05). TBUS, particularly BWT and Limberg score, may serve as a useful noninvasive tool for diagnosis, monitoring, and prognosis in CD.
To compare the efficacy and safety profile of arginine glutamate and L-ornithine-L-aspartate (LOLA) in treating mild hepatic encephalopathy (HE) and hyperammonemia in cirrhotic patients. This single-center, open-label, non-inferiority, randomized controlled trial (RCT) enrolled patients aged 18–75 years with cirrhosis and mild HE. The patients were randomly allocated in the ratio of 1:1 using a randomization table to be treated with intravenous administration of arginine glutamate or LOLA for 7 days. The primary end-point was the clinical improvement of mild HE. Secondary end-points included post-treatment change in blood ammonia level and the time to complete the number connection test (NCT)-A. Adverse events and adverse drug reactions were documented. From July 2020 to June 2021, 108 cirrhotic patients with mild HE were included and randomized to receive either arginine glutamate or LOLA for 7 days. Clinical improvement was observed in 88.9% of the patients receiving arginine glutamate and 90.7% of those having LOLA (between-group difference −1.9%, 95% confidence interval −13.3% to 9.6%), indicating non-inferiority of arginine glutamate to LOLA. The two groups showed comparable reductions in blood ammonia levels and improvements in time to complete NCT-A. The rate of adverse events was similar between the two groups, with only four cases reported adverse drug reactions. Both regimens effectively alleviated mild HE symptoms and reduced ammonia levels. Arginine glutamate showed non-inferiority to LOLA in terms of clinical improvement, ammonia reduction, and time to complete NCT-A, with no significant adverse events.
Hilar-type intrahepatic cholangiocarcinoma (H-ICC), which originates from the large bile ducts, tends to invade the hepatic hilus and results in malignant hilar biliary obstruction (MHBO). Compared with hilar cholangiocarcinoma (HC), H-ICC exhibits a more aggressive biological behavior and a dismal prognosis. We aimed to investigate the optimal biliary stenting strategy for the treatment of unresectable H-ICC. Patients with unresectable H-ICC who received endoscopic biliary stenting (EBS) between January 2012 and June 2019 were retrospectively included in this study. The prognostic factors of survival outcome, clinical success, duration of stent patency, and EBS-related adverse events were analyzed. Altogether 70 patients were enrolled, including 72.9% patients with multiple intrahepatic lesions and 44.3% with lymphatic metastasis. Jaundice control was achieved in 81.4% of the patients. Early cholangitis was the main treatment-related complication (17.1%). After successful stenting, systematic antitumor therapy was the only independent factor related to overall survival (hazard ratio [HR] 0.381, 95% confidence interval [CI] 0.218–0.668, p = 0.001). Plastic stenting was associated with clinical success (odds ratio [OR] 0.012, 95% CI 0.008–0.549, p = 0.012), stent patency (HR 6.773, 95% CI 2.221–20.653, p = 0.001), and early cholangitis (OR 5.000, 95% CI 1.006–24.841, p = 0.049). Bismuth classification IV was independently related to stent patency (HR 4.956, 95% CI 1.245–19.730, p = 0.023). For H-ICC-induced MHBO, metal stent placement may achieve better biliary drainage and, combined with systemic antitumor therapies, may further improve patient survival.
Upadacitinib (UPA) and vedolizumab (VDZ) have been approved to treat moderate-to-severe ulcerative colitis (UC); however, direct comparative data between these two regimens are lacking. We aimed to compare the effectiveness and safety of UPA and VDZ among patients with moderate-to-severe UC who had previously been treated with advanced therapies. Patients with moderate-to-severe UC receiving VDZ or UPA for at least 14 weeks following advanced therapy failure, including at least one anti-tumor necrosis factor (TNF) agent, between 2015 and 2024, were retrospectively recruited. Clinical response and remission were defined by the Partial Mayo Score and the Simple Clinical Colitis Activity Index. The safety profile during the treatment was also compared. Altogether 66 patients treated with VDZ and 22 patients with UPA were included. The median age of the VDZ and UPA groups was 38 and 37 years, respectively. Patients receiving UPA achieved significantly higher rates of corticosteroid-free remission after 52-week therapy (75.0% vs. 25.0%; adjusted odds ratio [aOR] 5.68, 95% confidence interval [CI] 1.50–21.00, p = 0.011); however, these patients were more likely to experience adverse events (AEs) (40.9% vs. 9.1%; aOR 4.60, 95% CI 1.20–17.00, p = 0.02), although medication discontinuation due to AEs was only noted in two (3.0%) patients receiving VDZ. No patients were hospitalized during the treatment period. UC patients receiving UPA achieved significantly higher rates of corticosteroid-free clinical remission but with more AEs, suggesting that decision-making based on disease severity and comorbidities can help guide the positioning of these therapies in UC.
Metabolic dysfunction–associated steatotic liver disease (MASLD) represents a major global health burden, yet its underlying mechanisms remain incompletely defined. We aimed to investigate the role of intestinal NOD-, LRR-, and pyrin-domain-containing protein 3 (NLRP3) inflammasome in the gut–liver axis to identify potential therapeutic targets for MASLD. Eight-week-old male mice were given a methionine-choline-deficient (MCD) diet for 4 weeks to induce MASLD-associated fibrosis. The functional role of NLRP3 was assessed using Vil1 cre Nlrp3 f/f mice with intestinal epithelial cell-specific Nlrp3 deletion. To evaluate the potential influence of the gut microbiota, Vil1 cre Nlrp3 f/f -MCD mice were co-housed with Nlrp3 f/f -MCD counterparts. The effect of butyrate was also evaluated in Vil1 cre Nlrp3 f/f -MCD mice via oral gavage for 3 weeks. The role of intestinal NLRP3 was further validated in a carbon tetrachloride (CCl 4 )-induced liver fibrosis model. Intestinal NLRP3 expression was markedly reduced in wild-type mice given MCD diet. Compared with Nlrp3 f/f -MCD mice, Vil1 cre Nlrp3 f/f -MCD mice developed more severe MASLD and exhibited impaired intestinal barrier integrity, whereas the co-housing condition alleviated hepatic pathology. Moreover, butyrate administration significantly improved hepatic steatosis and fibrosis in Vil1 cre Nlrp3 f/f -MCD mice. Mechanistic analysis revealed attenuated hepatic peroxisome proliferator-activated receptor α (PPARα) activation and enhanced hepatic activator protein (AP)-1 signaling in Vil1 cre Nlrp3 f/f -MCD mice, both of which improved under co-housing condition or butyrate treatment. Similarly, intestinal Nlrp3 deletion aggravated CCl 4 -induced liver fibrosis. Loss of intestinal Nlrp3 diminished butyrate production, inhibited PPARα expression, and enhanced AP-1 signaling, collectively intensifying MASLD progression.
To identify the risk factors for the survival of colorectal cancer (CRC) patients with type 2 diabetes mellitus (T2DM), compare the predictive performance of models based on different algorithms, and develop a risk score system to predict the survival risk of the target population. We analyzed data from the Hong Kong Hospital Authority Data Collaboration Laboratory (HADCL), including 10 749 CRC patients with T2DM from 2000 to 2020. We employed traditional statistical methods and machine learning algorithms to compare their performance using the area under the receiver operating characteristic curve (AUC). The SHapley Additive exPlanations (SHAP) analysis was conducted to identify risk factors and attribute model outputs. A risk score system was developed using the AutoScore-Survival package for risk stratification. Key predictors of CRC survival among T2DM patients included age at cancer diagnosis, sex, T2DM duration, alcohol consumption, central obesity, hypertension, levels of low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol, and serum potassium, and anti-lipid drug usage. Among the models assessed, the random survival forest showed the best performance. The risk score system was calibrated as follows: age at diagnosis, T2DM duration, LDL-C, glycated hemoglobin, creatinine, and body mass index. The AUCs for 1, 3, and 5 years of the tuned risk score system were 0.746, 0.718, and 0.677, respectively. The random survival forest model provides superior survival prediction compared to other models evaluated. A validated risk score system has been established, facilitating risk stratification for clinicians to manage these patients.
Unresectable ampullary cancer (AC) is a rare disease entity. The risk factors for recurrent biliary obstruction (RBO) following endoscopic biliary stenting (EBS) for unresectable AC remain unknown. In this study we aimed to evaluate the cumulative RBO rate and to identify risk factors for RBO following palliative EBS in patients with unresectable AC. This multicenter retrospective observational study enrolled consecutive patients with unresectable AC who had undergone palliative EBS between April 2011 and December 2021. The cumulative rate of and risk factors for RBO following palliative EBS were evaluated via multivariate analysis. The study analysis comprised 107 patients with a median age of 84 years (interquartile range 79–88 years). Plastic stents (PSs) and self-expandable metal stents (SEMSs) were placed in 53 and 54 patients, respectively. Functional success was accomplished in 104 (97.2%) patients. Of these, RBO occurred in 62 (59.6%) patients, with obstruction and complete/partial migration occurring in 47 and 15 patients, respectively. The median time to RBO was 190 days. Multivariate analysis showed that PS was associated with a higher rate of RBO compared to SEMS (hazard ratio [HR] 2.48; P < 0.01) and that the presence of common bile duct stones/sludge immediately after EBS was an independent risk factor for RBO (HR 1.99; P = 0.04). The use of SEMS compared to PS during EBS reduced the time to RBO in patients with unresectable AC. Common bile duct stones/sludge immediately after EBS was a risk factor for RBO.
Single-balloon enteroscopy (SBE) is an effective tool for the detection of small intestine lesions. Because it is conventionally performed by two operators, the efficacy of single-operator SBE method has not yet been elucidated. We aimed to evaluate the diagnostic yield, total enteroscopy rate, procedure time, and complications of single-operator SBE for small intestinal disease. This was a single-center, retrospective study including consecutive patients who underwent single-operator SBE for suspicious small intestinal disorders or required therapeutic interventions between December 2014 and January 2019. The SBE procedures were performed by four endoscopists. Diagnostic yield, total enteroscopy rate, procedure time, incubation depth, and complications were analyzed, and stratification analysis was performed. Altogether 922 patients with 1422 SBE procedures were included for analysis, among whom 250, 172, and 500 patients underwent SBE via the oral route, the anal route and a combined route, respectively. The overall diagnostic yield was 78.52% (724/922). And 253 patients achieved total enteroscopy, with a total enteroscopy rate of 56.10%. The average procedure time for the oral and anal routes were 69.28 ± 14.72 min and 64.95 ± 13.87 min, respectively. While the incubation depth was 389.95 ± 131.42 cm and 191.81 ± 83.67 cm, respectively. Jejunal perforation was observed in one patient, which was managed by endoclips. Stratification analysis showed that the diagnostic yield and total enteroscopy rate significantly increased with operation experience together with decreased procedure time. Single-operator SBE is effective and safe for the detection of small intestinal lesions, and is easy to master.
Functional constipation (FC), a common functional gastrointestinal disorder, is usually overlapping with upper gastrointestinal symptoms (UGS). We aimed to explore the clinical characteristics of patients with FC overlapping UGS along with the related risk factors. The differences in the severity of constipation symptoms, psychological state, quality of life (QoL), anorectal motility and perception function, autonomic function, and the effect of biofeedback therapy (BFT) among patients with FC in different groups were analyzed, along with the risk factors of overlapping UGS. Compared with patients with FC alone, those with FC overlapping UGS had higher scores in the Patient Assessment of Constipation Symptoms and Self-Rating Anxiety Scale and lower scores in the Short Form-36 health survey ( P < 0.05). Patients with FC overlapping UGS also had lower rectal propulsion, more negative autonomic nervous function, and worse BFT efficacy ( P < 0.05). Overlapping UGS, especially overlapping functional dyspepsia, considerably affected the severity of FC. Logistic regression model showed that age, body mass index (BMI), anxiety, exercise, and sleep quality were independent factors influencing overlapping UGS in patients with FC. Overlapping UGS reduces the physical and mental health and the QoL of patients with FC. It also increases the difficulty in the treatment of FC. Patient's age, BMI, anxiety, physical exercise, and sleep quality might be predictors for FC overlapping UGS.
