Journal of Gastroenterology and Hepatology最新文献

Background and aim: Peutz-Jeghers syndrome (PJS) and juvenile polyposis syndrome (JPS) are autosomal dominant diseases associated with high cancer risk. In Japan, knowledge about the prevalence and incidence of PJS and JPS is lacking despite being crucial for providing appropriate medical support. We aimed to determine the prevalence and incidence of these diseases.

Methods: In 2022, a nationwide questionnaire survey was conducted to determine the number of patients with PJS or JPS by sex and the number of newly confirmed cases from 2019 to 2021. The target facilities included gastroenterology, pediatrics, and pediatric surgery departments, which were stratified into seven classes on the basis of the total number of beds. We randomly selected target facilities using different extraction rates in each class, resulting in 1748/2912 facilities (extraction rate: 60%) as the final sample. We calculated the estimated number of patients using the response and extraction rates.

Results: A total of 1077 facilities responded to the survey. The estimated numbers of patients with PJS and JPS were 701 (95% confidence interval [CI]: 581-820) and 188 (95% CI: 147-230), respectively. The 3-year period prevalences of PJS and JPS were 0.6/100000 and 0.15/100000, whereas the incidences in 2021 were 0.07/100000 and 0.02/100000, respectively. Male patients constituted 53.5% and 59.6% in the PJS and JPS groups, respectively.

Conclusions: We determined the prevalence and incidence of PJS and JPS in Japan for the first time. Further research is needed to obtain more detailed information, including the clinical differences and outcomes in Japan.

Background and aim: We aimed to assess the gene expression profiles of nonlesional small bowels in patients with Crohn's disease (CD) to identify its accompanying molecular alterations.

Methods: We performed RNA sequencing of the uninflamed small bowel tissues obtained from 70 patients with ileal CD and 9 patients with colon cancer (non-CD controls) during bowel resection. Differentially expressed gene (DEG) analyses were performed using DESeq2. Gene set enrichment, correlation, and cell deconvolution analyses were applied to identify modules and functionally enriched transcriptional signatures of CD.

Results: A comparison of CD patients and non-CD controls revealed that of the 372 DEGs, 49 protein-coding genes and 5 long non-coding RNAs overlapped with the inflammatory bowel disease susceptibility loci. The pathways related to immune and inflammatory reactions were upregulated in CD, while metabolic pathways were downregulated in CD. Compared with non-CD controls, CD patients had significantly higher proportions of immune cells, including plasma cells (P = 1.15 × 10^-4), and a lower proportion of epithelial cells (P = 1.12 × 10^-4). Co-upregulated genes (M14 module) and co-downregulated genes (M9 module) were identified in CD patients. The M14 module was enriched in immune-related genes and significantly associated with the responses to anti-tumor necrosis factor (TNF) therapy. The core signature of the M14 module was comprised of six genes and was upregulated in nonresponders to anti-TNF therapy of five independent cohorts (n = 163), indicating acceptable discrimination ability (area under the receiver operating characteristic curve of 75-86%).

Conclusions: The differences in gene expression and cellular composition between CD patients and non-CD controls imply significant molecular alterations, which are associated with the response to anti-TNF treatment.

Background and aim: To reduce bacterial contamination after reprocessing, various new designs of duodenoscopes have been developed to better expose the elevator complex for cleaning. We compared the rates of bacterial contamination and organic residue in disposable distal cap duodenoscopes and detachable elevator duodenoscopes after manual cleaning and high-level disinfection (HLD), as well as their cost-effectiveness.

Methods: A total of 162 duodenoscopes were randomly assigned to either Group A (disposable distal caps; n = 81) or Group B (detachable elevator; n = 81). A total of 324 samples from the elevator were collected for culture following manual cleaning (n = 81 in each group) and HLD (n = 81 in each group), followed by the adenosine triphosphate (ATP) testing for organic residue.

Results: After manual cleaning, there was no difference in bacterial contamination rates (8.6% vs. 8.6%; p = 1.00) and mean ATP levels (164.6 ± 257.5 vs. 158.1 ± 286.1 RLUs; p = 0.88) between Groups A and B. After HLD, no bacterial contamination was observed in either group and the mean ATP levels were very low with no significant difference between the two groups (30.1 ± 45.3 vs. 37.5 ± 51.9 RLUs; p = 0.68). The expense in reprocessing (excluding the scope cost) for Group A was lower (2099 USD) than Group B (3854 USD) in providing comparable scope cleanliness.

Conclusion: After manual cleaning, the bacterial contamination rate and organic residue levels in detachable elevator duodenoscopes and disposable distal caps duodenoscopes were comparable. No bacterial contamination was detected in either type of duodenoscope after reprocessing. Apart from the initial differences in scope cost, the disposable distal cap duodenoscope had lower cost on disposable items to have comparable disinfection result.

Inflammatory bowel disease (IBD) is an inflammatory disease that occurs to the intestinal tract. Many patients with IBD often develop anemia and often receive oral iron supplementation. Many of them develop non-compliance with oral iron therapy, but the mechanisms are not well understood. We interrogated whether colonic epithelial iron overload impacts cell viability and disease severity. We observed increased expression of iron importers and iron accumulation in mature colonocytes in dextran sulfate sodium (DSS)-induced acute colitis and in humans with active colitis. Administration of hepcidin increased epithelial iron overload and aggravated colonic inflammation in DSS-treated mice and IL10^-/- mice. Hepcidin-induced iron accumulation increased colonic epithelial death, which was prevented by treatment with Trolox, a vitamin E analog and a scavenger of lipid peroxides. By using cultured Caco-2 cells, we showed that iron and inflammatory cytokines (TNF-α and IL-1β) induced a synergistic increase in the number of necrotic cells. We then showed that the combined treatment by hepcidin and cytokines increased labile iron content and lipid peroxidation in Caco-2 cells. Moreover, liproxstatin-1, a ferroptosis inhibitor, and deferoxamine, an iron chelator, both abolished the hepcidin/cytokines induced death of Caco-2 cells, suggesting ferroptosis. We further elucidated that inflammatory cytokines promote lipid peroxidation and ferroptosis by inducing NOX1-dependent exhaustion of reduced glutathione (GSH). Collectively, our findings demonstrate that the inflammatory context predisposes colonic epithelial cells to iron overload mediated ferroptosis, exacerbating colonic inflammation.

Background and aim: We aimed to develop and validate a simple capsule endoscopy (CE) training assessment tool, the Capsule Endoscopy Training Assessment (CETA), and prospectively use it to analyze the learning progression achieved by participants in our CE training program.

Methods: Over a 3-year period, all participants in our CE training program completed pre-training and post-training CETA, ranging between 0% and 100%, and encompassing theoretical questions and interpretation of segmented CE videos. We compared the mean differences in overall, theoretical, and practical pre-training and post-training CETA, and assessed the influence of previous endoscopic experience (upper gastrointestinal endoscopy [UGE], colonoscopy, device-assisted enteroscopy [DAE] and CE) using generalized linear models.

Results: Fifty-seven participants were included. After training, there was a significant increase in participants' overall (mean difference, 26.3; 95% confidence interval [CI], 20.70 to 31.83), theoretical (mean difference, 27.2; 95% CI, 19.81 to 34.57), and practical (mean difference, 25.9; 95% CI, 20.09 to 31.63) CETA components. Compared to those without experience, participants with previous endoscopic experience demonstrated a smaller increase in overall CETA after training (UGE, rate ratio, 0.76; 95% CI, 0.63 to 0.91; colonoscopy (rate ratio, 0.80; 95% CI, 0.67 to 0.95; DAE (rate ratio, 0.84; 95% CI, 0.73 to 0.97; CE, rate ratio, 0.81; 95% CI, 0.72 to 0.92, respectively).

Conclusion: CETA is a valid and useful tool in assessing the learning progression achieved by participants following the CE training program. We demonstrated a significant improvement in participants' CETA after training, being the least experienced participants in endoscopic procedures who benefited the most from CE training.

Background and aim: Optical diagnosis of superficial nonampullary duodenal epithelial tumors using white-light imaging (WLI) and/or narrow-band imaging with magnifying endoscopy (NBI-ME) is used to guide the treatment strategy and avoid biopsy-induced fibrosis. However, the effectiveness of this approach has not been elucidated. We conducted a systematic review and meta-analysis aiming to investigate the diagnostic yield between Vienna classification category 3 (VCL C3) and categories 4 or 5 (VCL C4/C5) using biopsy, WLI, NBI-ME, and WLI + NBI-ME.

Methods: A literature search identified studies on the diagnosis of superficial nonampullary duodenal epithelial tumors using biopsy, WLI, or NBI-ME. A bivariate random-effects model was utilized to analyze the summary estimates of sensitivity and specificity, as well as the area under the summary receiver operating characteristic curves for diagnosing VCL C4/C5.

Results: Ultimately, 13 studies were included in the meta-analysis. For the diagnosis of VCL C4/C5, summary estimates of sensitivity, specificity, and area under the curve were for biopsy 47% (95% confidence interval: 37-58), 86% (79-91), and 0.745; for WLI 80% (65-89), 80% (70-87), and 0.859; for NBI-ME were 72% (61-81), 76% (68-85), and 0.811; and for WLI + NBI-ME 88% (67-96), 87% (51-98), and 0.929, respectively.

Conclusions: WLI, NBI-ME, and WLI + NBI-ME showed high values for sensitivity and area under the curve. Biopsies can be replaced by WLI, NBI-ME, and WLI + NBI-ME for the preoperative diagnosis of superficial nonampullary duodenal epithelial tumors. However, further accumulation of research findings is needed.

Background: Whether the progression of precursor lesions or the occurrence of cancer is influenced by lifestyle factors in carriers of genetic mutations has not been fully investigated, especially in Asian patients of hereditary colorectal cancer (CRC) syndrome.

Methods: Patients at a high risk of hereditary CRC were included. For polyposis CRC syndromes, colorectal polyp burden was measured using at least 60 images per colonoscopy in each patient and classified into five stages using the International Society for Gastrointestinal Hereditary Tumours staging system according to the polyp number and size. Increase in tumor burden stage for polyposis CRC syndrome and the occurrence of CRC or any cancer for Lynch syndrome were analyzed according to lifestyle factors.

Results: Ninety-six patients with suspected hereditary polyposis CRC syndrome and 106 patients with Lynch syndrome were recruited. For polyposis CRC syndromes, multivariate analysis showed that exposure to smoking and > 100 polyps independently predicted a high risk of increased polyp burden (p = 0.008 and p = 0.012, respectively). Significant genetic mutations or phenotype of polyposis syndromes were significantly associated with an increased polyp burden. For Lynch syndrome, smokers showed to be diagnosed with CRC in younger age than never-smokers (42.2 years vs. 49.0 years; p = 0.021), and heavy drinkers had high risk for occurrence of CRC (HR, 2.381, 95% CI, 1.338-4.236; p = 0.003) and any cancer (HR, 2.254; 95% CI, 1.334-3.806; p = 0.002).

Conclusions: The lifestyle factors (smoking and alcohol consumption) were associated with increasing precursor lesions and occurrence of cancer in patients with hereditary CRC syndrome. Lifestyle modifications may reduce the risk of hereditary CRC in carriers.

Background and aim: Ulcerative colitis (UC) is a chronic inflammatory disease driven by immune dysregulation. PANoptosis, a novel form of programmed cell death, has been implicated in inflammatory diseases, but its specific role in UC remains unclear. This study aimed to identify PANoptosis-related genes (PRGs) that may contribute to immune dysregulation in UC.

Methods: Using bioinformatics analysis of the GEO databases, we identified seven hub PRGs. Based on these genes, we developed a predictive model to differentiate UC patients from healthy controls, and evaluated its diagnostic performance using ROC curve analysis. We further conducted functional enrichment, GSVA, and immune infiltration analyses. Immunohistochemistry (IHC) was used to validate the expression of hub genes in UC patients.

Results: The prediction model, based on the seven hub genes, exhibited diagnostic ability in discriminating UC patients from controls. Furthermore, these hub PRGs were found to be associated with immune cells, including dendritic cells, NK cells, macrophages, regulatory T cells (Tregs), and CD8+ T cells. They were also linked to key signaling pathways implicated in UC pathogenesis, such as IFNγ, TNFα, IL6-and JAK-STAT3, as well as hypoxia and apoptosis. Immunohistochemistry analysis validated the expression levels of hub PRGs in UC patients using paraffin sections of intestinal biopsy specimens.

Conclusions: This study identified PANoptosis-related genes with potential diagnostic value for UC and suggest that PANoptosis may contribute to the pathogenesis of UC by regulating specific immune cells and interacting with key signaling pathways. This highlights the potential importance of PANoptosis-related genes as therapeutic targets in UC management.