Journal of Digestive Diseases最新文献

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.

Objectives: 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.

Methods: 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^creNlrp3^f/f mice with intestinal epithelial cell-specific Nlrp3 deletion. To evaluate the potential influence of the gut microbiota, Vil1^creNlrp3^f/f-MCD mice were co-housed with Nlrp3^f/f-MCD counterparts. The effect of butyrate was also evaluated in Vil1^creNlrp3^f/f-MCD mice via oral gavage for 3 weeks. The role of intestinal NLRP3 was further validated in a carbon tetrachloride (CCl₄)-induced liver fibrosis model.

Results: Intestinal NLRP3 expression was markedly reduced in wild-type mice given MCD diet. Compared with Nlrp3^f/f-MCD mice, Vil1^creNlrp3^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^creNlrp3^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^creNlrp3^f/f-MCD mice, both of which improved under co-housing condition or butyrate treatment. Similarly, intestinal Nlrp3 deletion aggravated CCl₄-induced liver fibrosis.

Conclusion: Loss of intestinal Nlrp3 diminished butyrate production, inhibited PPARα expression, and enhanced AP-1 signaling, collectively intensifying MASLD progression.

Objectives: 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.

Methods: 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).

Results: 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.

Conclusions: 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.

Objective: 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).

Methods: 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.

Results: 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.

Conclusions: 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.

Objective: 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.

Methods: 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.

Results: 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.

Conclusion: 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.

Objectives: 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.

Methods: 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.

Results: 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.

Conclusions: 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.

Dyslipidemia is common in patients with metabolic dysfunction-associated steatotic liver disease (MASLD) and, along with other metabolic comorbidities, accounts for an increased cardiovascular risk. Effective treatment of dyslipidemia not only reduces such risk but may have a beneficial effect on MASLD as well. Here we reviewed published data on the efficacy and safety of available hypolipidemic treatments for MASLD. Statins are the mainstay of hypolipidemic therapy for MASLD. In patients with compensated cirrhosis, statins are safe and can improve the risks of decompensation and hepatocellular carcinoma as well as mortality. However, in those with decompensated cirrhosis, statins should not be used unless there are strong indications that outweigh the risk of adverse events. Studies on proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors acting as the second-line therapy in MASLD remain scarce. Preliminary clinical data support their protective roles in MASLD; however, preclinical data raise concerns regarding safety, in particular with complete PCSK9 inhibition due to hepatocyte lipid accumulation. While more evidence is required to elucidate the role of PCSK9 inhibitors, statins should be used for the treatment of hyperlipidemia in patients with MASLD according to their cardiovascular risk stratification.