Helicobacter pylori infection exacerbates metabolic dysfunction-associated steatotic liver disease through lipid metabolic pathways: a transcriptomic study.

BACKGROUND: The relationship between Helicobacter pylori (H. pylori) infection and metabolic dysfunction-associated steatotic liver disease (MASLD) has attracted increased clinical attention. However, most of those current studies involve cross-sectional studies and meta-analyses, and experimental mechanistic exploration still needs to be improved. This study aimed to investigate the mechanisms by which H. pylori impacts MASLD. METHODS: We established two H. pylori-infected (Cag A positive and Cag A negative) mouse models with 16 weeks of chow diet (CD) or high-fat diet (HFD) feeding. Body weight, liver triglyceride, blood glucose, serum biochemical parameters, inflammatory factors, and insulin resistance were measured, and histological analysis of liver tissues was performed. Mouse livers were subjected to transcriptome RNA sequencing analysis. RESULTS: Although H. pylori infection could not significantly affect serum inflammatory factor levels and serum biochemical parameters in mice, serum insulin and homeostatic model assessment for insulin resistance levels increased in CD mode. In contrast, H. pylori Cag A + infection significantly aggravated hepatic pathological steatosis induced by HFD and elevated serum inflammatory factors and lipid metabolism parameters. Hepatic transcriptomic analysis in the CD groups revealed 767 differentially expressed genes (DEGs) in the H. pylori Cag A + infected group and 1473 DEGs in the H. pylori Cag A- infected group, and the "nonalcoholic fatty liver disease" pathway was significantly enriched in KEGG analysis. There were 578 DEGs in H. pylori Cag A + infection combined with the HFD feeding group and 820 DEGs in the H. pylori Cag A- infected group. DEGs in the HFD groups were significantly enriched in "fatty acid degradation" and "PPAR pathway." Exploring the effect of different Cag A statuses on mouse liver revealed that fatty acid binding protein 5 was differentially expressed in Cag A- H. pylori. DEG enrichment pathways were concentrated in the "PPAR pathway" and "fatty acid degradation." CONCLUSIONS: Clinicians are expected to comprehend the impact of H. pylori on MASLD and better understand and manage MASLD. H. pylori infection may exacerbate the development of MASLD by regulating hepatic lipid metabolism, and the H. pylori virulence factor Cag A plays a vital role in this regulation.

M2 macrophages participate in ILC2 activation induced by Helicobacter pylori infection.

Helicobacter pylori (H. pylori) causes a diversity of gastric diseases. The host immune response evoked by H. pylori infection is complicated and can influence the development and progression of diseases. We have reported that the Group 2 innate lymphocytes (ILC2) were promoted and took part in building type-2 immunity in H. pylori infection-related gastric diseases. Therefore, in the present study, we aim to clarify how H. pylori infection induces the activation of ILC2. It was found that macrophages were necessary for activating ILC2 in H. pylori infection. Mechanistically, H. pylori infection up-regulated the expression of indoleamine 2,3-dioxygenase (IDO) in macrophages to induce M2 polarization, and the latter secreted the alarmin cytokine Thymic Stromal Lymphopoietin (TSLP) to arouse ILC2.

Safety and efficacy of ESD for laterally spreading tumors with hemorrhoids close to the dentate line.

BACKGROUND: Endoscopic submucosal dissection (ESD) is a curative treatment for laterally spreading tumors (LSTs). However, the outcomes of ESD for LSTs with hemorrhoids remain largely unknown. Our study aimed to evaluate the usefulness of ESD in managing LSTs with hemorrhoids. MATERIAL AND METHODS: We retrospectively collected 418 consecutive LST patients treated with ESD between 2011 and 2023. A retrospective comparative analysis was conducted. RESULTS: There were 85 patients included in the hemorrhoids group and 333 patients included in the other group. The en-bloc resection rate, R0 resection rate, and curative resection rate were comparable in these two groups (p > 0.05). The LSTs with hemorrhoids have a significantly higher intraoperative bleeding rate during ESD when compared to the other group (12.9% vs. 5.4%, p = 0.028). Rates of intraoperative perforation and anal pain in the hemorrhoid group were significantly higher than those in the no-hemorrhoid group (2.4% vs. 0%, p = 0.041; 9.4% vs.0.6%, p < 0.001; respectively). Moreover, most of the related manifestations caused by hemorrhoids were relieved to various degrees after ESD. CONCLUSIONS: ESD is a safe and effective treatment strategy for LSTs with hemorrhoids. A multi-center and prospective study should be conducted in the future to validate our results.

An update: is there a relationship between H. pylori infection and nonalcoholic fatty liver disease? why is this subject of interest?

Helicobacter pylori (H. pylori) infection is thought to impact various extragastric diseases, including nonalcoholic fatty liver disease (NAFLD), the most common chronic liver disease. Meanwhile, the pathogenesis of NAFLD needs further research, and effective treatment for this disease remains elusive. In this mini-review, we enumerate and ponder on the evidence demonstrating an association between H. pylori infection and NAFLD. Primarily, we delve into high-quality meta-analyses and clinical randomized controlled trials focusing on the association studies between the two. We also discuss clinical studies that present opposite conclusions. In addition, we propose a mechanism through which H. pylori infection aggravates NAFLD: inflammatory cytokines and adipocytokines, insulin resistance, lipid metabolism, intestinal barrier and microbiota, H. pylori outer membrane vesicles and H. pylori-infected cell-extracellular vesicles. This mini-review aims to further explore NAFLD pathogenesis and extragastric disease mechanisms caused by H. pylori infection.

The feasibility of endoscopic resection for colorectal laterally spreading tumors.

The present study aimed to investigate the feasibility and safety of endoscopic resection for colorectal laterally spreading tumors (LSTs) in different size groups. This retrospective study included 2699 patients with LSTs who underwent endoscopic treatment at the Second Xiangya Hospital of Central South University from May 2012 to February 2022. The patient baseline and procedure outcomes were compared between the < 5 cm group, 5-10 cm group, and ≥ 10 cm group. Meanwhile, lesions larger than 5 cm in diameter were longitudinally compared for endoscopic safety using ESD with surgical operation outcomes. There were 2105 patients in the < 5 cm group, 547 patients in the 5-10 cm group, and 47 patients in the ≥ 10 cm group. En bloc resection and R0 resection rates, the incidence of adverse events, length of stay (LOS), and medical costs significantly differed between the groups (P < 0.01). Comorbidity of diabetes or hypertension, history of antithrombotic drug use, lesion size, location, gross type, endoscopic procedures selection, and circumferential extent of the mucosal defect were independent risk factors for delayed bleeding (P < 0.05). En bloc resection, R0 resection, and lesion canceration were associated with local recurrence. For lesions larger than 5 cm in diameter, ESD had similar R0 resection and local recurrence rates compared with a surgical operation but a lower en bloc rate, LOS, and medical costs. Expert endoscopists can significantly increase en bloc and R0 resection rates and reduce the incidence of adverse events. Endoscopic resection results distinguish in different size groups of colorectal LSTs, yet its safety and feasibility are not inferior to a surgical operation.

Peroral Endoscopic Myotomy for Achalasia in Older Adults: A Retrospective Analysis of 39 Cases with a Minimum Follow-Up of 5 Years.

Peroral endoscopic myotomy (POEM) has demonstrated favorable short-term safety and efficacy in older adults, while a comprehensive understanding of the long-term outcomes were vague. We aimed to evaluate clinical outcomes in older adults' 5-year postop after undergoing POEM to treatment achalasia. Older adults from a single hospital who received POEM between January 2010 and January 2017 were analyzed. Older persons were reached to evaluate their symptoms at present and encouraged repeat examinations for objective follow-up. The clinical success, POEM-related indicators, POEM-related adverse events, and quality of life were assessed. Thirty-nine older adults with a mean age of 70.82 ± 4.72 who underwent POEM were studied at a mean 84.23 ± 25.06 month follow-up. The preoperative diagnosis was achalasia type I in 7 older adults, achalasia type II in 26 older adults, and achalasia type III in 2 older adults. Sixteen older adults had prior treatment and 21 older adults suffered from comorbidities. The median operative time was 50 (25-120) minutes, and perioperative adverse events were recorded in four older adults. The current Eckardt scores were significantly lower than that before POEM (2.08 ± 2.12 vs. 6.58 ± 1.78, P < 0.001). Besides, long-term clinical success was gained in 66.7% of older adults. Three older adults received postop treatment for symptom recurrence. Ultimately, 80.6% of old adults expressed satisfaction with POEM, while 27.8% of older adults suffered from symptomatic reflux. In conclusion, POEM can provide symptomatic improvement in a large proportion of older adults with achalasia at 5-year postop.

Investigation of early neoplastic transformation and premalignant biology using genetically engineered organoid models.

Organoid modeling is a powerful, robust and efficient technology faithfully preserving physiological and pathological characteristics of tissues of origin. Recently, substantial advances have been made in applying genetically engineered organoid models to study early tumorigenesis and premalignant biology. These efforts promise to identify novel avenues for early cancer detection, intervention and prevention. Here, we highlight significant advancements in the functional characterization of early genomic and epigenomic events during neoplastic evolution using organoid modeling, discuss the application of the lineage-tracing methodology in organoids to study cancer cells-of-origin, and review future opportunities for further development and improvement of organoid modeling of cancer precursors.

Peroral Endoscopic Myotomy for Pediatric Achalasia: A Retrospective Analysis of 21 Cases With a Minimum Follow-Up of 5 Years.

Background: Peroral endoscopic myotomy (POEM) has shown promising short-term safety and efficacy in pediatric patients, while long-term outcomes are largely unknown. This study aimed to assess the clinical effects of POEM for pediatric achalasia who had a follow-up of at least 5 years. Methods: Pediatric patients from a single center who underwent a POEM between October 2011 and November 2016 were, respectively, collected and analyzed for long-term clinical outcomes. Patients were contacted to evaluate their current symptoms and encouraged repeat endoscopy and manometry. The clinical success, procedure-related parameters, adverse events, gastroesophageal reflux disease after POEM, and quality of life were evaluated. Results: A total of twenty-four patients who underwent POEM in our center were studied, with a mean age of 14.42 ± 2.65. Two of the 24 patients (8.3%) had previous treatment. The mean of the procedure time was 58.67 ± 19.10 min, 8.3% (2/24) of patients experienced perioperative adverse events. The current symptom scores were obtained from 21 patients at a mean follow-up of 92.57 months, the remainder were lost to follow-up after a mean of 38 months. Eckardt scores were significantly improved from preoperative baseline (preoperative 7.67 ± 1.62 vs. current 0.86 ± 1.28, P < 0.001). Long-term overall success was achieved in 95.8% of patients and none required retreatment for symptoms. 12.5% of patients were suffered from clinical reflux. 76.2% of patients expressed satisfaction with POEM. No severe adverse events were observed during the operation and the 5-years follow-up. Conclusion: POEM resulted in successful symptomatic mitigation in a majority of pediatric patients after 5 years. A multi-center large-scale, prospective study is necessary for a confirmed conclusion.

Comparison between submucosal tunneling endoscopic resection and endoscopic full-thickness resection for gastric stromal tumors originating from the muscularis propria layer.

BACKGROUND: Both submucosal tunneling endoscopic resection (STER) and endoscopic full-thickness resection (EFTR) are effective method for treating gastric gastrointestinal stromal tumors (GISTs); however, little is known about the comparison between STER and EFTR. The aim of the study was to compare the safety and efficacy of STER and EFTR for treating gastric GIST. METHODS: We retrospectively collected the clinical data about patients with gastric GISTs who received STER or EFTR at our hospital from April 2011 to June 2016. Epidemiological data (gender, age), tumor size, procedure-related parameters, complications, length of stay, cost and follow-up data were compared between STER and EFTR. RESULTS: A total of 52 patients were enrolled, and 20 of them received STER, while the other 32 cases received EFTR. There was no significant difference between the two groups in terms of gender, age, concomitant diseases, tumor size, en bloc resection rate, operation time, complications, pathohistological grade of GIST, hospital stay and cost (P > 0.05). However, patients who received EFTR had a longer suture time and needed more clips to close the gastric-wall defect (STER vs EFTR, 291.5 ± 68.7 vs 380.6 ± 96.9s and 6.0 ± 1.2 vs 7.6 ± 1.6, P < 0.05). No recurrence was noted in the STER and EFTR groups during a mean follow-up of 10.9 and 23.8 months, respectively. CONCLUSIONS: The treatment efficacy between STER and EFTR for treating gastric GISTs was comparable, and a large-scale, randomized study is necessary for a more confirmed conclusion.

Comparison between submucosal tunneling endoscopic resection and video-assisted thoracoscopic surgery for large esophageal leiomyoma originating from the muscularis propria layer.

BACKGROUND: Submucosal tunneling endoscopic resection (STER) has been proved to be safe and effective for removal of esophageal leiomyoma originating from the muscularis propria (MP) layer. However, there are still technical challenges for tumors ≥35 mm due to the limited space of the submucosal tunnel. The aim of the study was to estimate the safety and efficacy of STER for large esophageal leiomyoma originating from the MP layer as well as compare its efficacy with video-assisted thoracoscopic surgery (VATS), which is a standard procedure for treating esophageal leiomyoma. METHODS: We retrospectively collected the clinical data of the patients with esophageal leiomyoma of 35-55 mm who underwent STER or VATS at our hospital between January 2010 and December 2014. Epidemiological data (gender, age), tumor location, tumor size, procedure-related parameters, complications, length of stay and cost were compared between STER and VATS. RESULTS: A total of 31 patients were enrolled, and 18 patients underwent STER and the other 13 received VATS. There was no significant difference between the two groups in gender, age, tumor location, tumor size, complications and rate of en bloc resection (P > 0.05). However, patients in the STER groups had a shorter operation time, a less decrease in hemoglobin level, a shorter length of hospital stay and a decreased cost (P < 0.05). No recurrence was noted in the STER and VATS groups during a mean follow-up of 10.9 and 30.8 months, respectively. CONCLUSIONS: The treatment efficacy was comparable between the STER and VATS for esophageal leiomyoma of 35-55 mm. However, STER is superior to VATS in a shorter operation time, a less decrease in hemoglobin level, a shorter length of hospital stay and a decreased cost.