Digestive Diseases最新文献

Introduction: Lenvatinib has been widely used for the treatment of advanced hepatocellular carcinoma (HCC). Some adverse events, including diarrhea, have been reported for lenvatinib. Diarrhea may be associated with the changes in the intestinal microbiome; however, the underlying mechanism has not been elucidated.

Aim: In this study, we aimed to investigate the relationship between the intestinal microbiome and diarrhea caused by lenvatinib via analysis of fecal samples collected before treatment.

Methods: A total of 21 patients with advanced HCC who were treated with lenvatinib were enrolled. Fecal samples were collected from patients. The patients were divided into diarrhea (n = 8) and nondiarrhea groups (n = 12). We compared the characteristics of patients, incidence of adverse events, composition of the intestinal microbiome, and enrichment of functional pathways between both groups using QIIME2 and PICRUSt2.

Results: The median age of the two groups was 73 years. The nondiarrhea group comprised a relatively higher number of male patients than the diarrhea group; however, there were no significant differences in patient characteristics between both groups. The proportion of the microbiome was similar, and alpha and beta diversities were not significantly different between both groups. The relative abundance of order Bacteroidales, including Parabacteroides and Prevotella, was higher in the diarrhea group than in the nondiarrhea group. PICRUSt2 analysis showed some metabolic pathways, including butanoate (butyrate) metabolism, were enriched in the nondiarrhea group when compared with those in the diarrhea group.

Conclusion: Differences in the intestinal microbiomes and their functions may influence the incidence of diarrhea during lenvatinib treatment.

Introduction: Abdominal obesity increases the risk of gastroesophageal reflux disease (GERD). This study aimed to determine the association between GERD and abdominal fat area quantified by computed tomography (CT).

Methods: We analyzed the effect of abdominal fat area on gastroesophageal reflux symptoms and erosive esophagitis using logistic regression models in 5,338 participants who underwent abdominal fat measurement CT and screening esophagogastroduodenoscopy.

Results: Participants with reflux symptoms and erosive esophagitis were diagnosed in 1,168 (21.9%) and 671 (12.5%), respectively. Multivariate analysis showed that subcutaneous and visceral fat areas were significantly associated with reflux symptoms and erosive esophagitis. The adjusted odds ratio (OR) in the fourth quartile of visceral fat area compared with that in the lowest quartile was 1.98 (95% confidence interval (CI) 1.63-2.39) for reflux symptoms and 2.33 (95% CI 1.80-3.01) for erosive esophagitis. Visceral fat area had a stronger effect in the younger age-group. In the group <50 years, the adjusted OR in fourth quartile of visceral fat area was 2.70 (95% CI 1.86-3.94) for reflux symptoms and 3.59 (95% CI 2.22-5.80) for erosive esophagitis. High visceral-to-subcutaneous fat ratio (VSR) increased the risk of reflux symptoms and erosive esophagitis in participants with body mass index <25 kg/m2 and normal waist circumference.

Conclusion: Subcutaneous and visceral fat areas were associated with an increased risk of reflux symptoms and erosive esophagitis. High VSR increased the risk of reflux symptoms and erosive esophagitis in participants with normal body weight and waist circumference.

Introduction: Glomus tumor (GT) is a rare mesenchymal neoplasm that can be found anywhere throughout the body, including the stomach. Our goal was to present a case and a systematic review of the literature, reporting clinical, radiological, surgical, and pathological features of the disease.

Methods: We reviewed Pubmed and SCOPUS for all case reports and case series published after 2000. Papers written in languages different from English and letters to the editor were excluded. Screening and data extraction were performed following the PRISMA guidelines.

Results: A total of 89 studies were included in the systematic review, consisting of 187 cases of gastric glomus tumor. Mean age was 52 (18-90); most patients were female (61%). The most common clinical presentation was epigastric pain (33.9% of cases). The gastric antrum was the most frequently involved site (75.3%). Mean tumor size was 2.82 cm (0.8-17). Preoperative diagnosis was achieved in 22 cases, mostly by endoscopic ultrasound (EUS)-guided biopsy. Wedge resection was performed in 62% of treated patients. Smooth muscle actin was expressed in all cases with available immunohistochemistry. Malignant GT was reported in 11 cases.

Discussion: Epigastric pain and bleeding were the most common symptoms at presentation in patients with diagnosis of glomus tumor. EUS-guided fine needle aspiration can be useful for preoperative diagnosis. Endoscopic elastosonography is a promising tool for the differential diagnosis of gastric submucosal lesions, including glomus tumors. The treatment of choice is wedge resection with adequate free margins. A laparoscopic approach is warranted when technically feasible. Since malignant gastric GTs have been described, long-term follow-up is suggested after surgical excision.

Background: Peritoneal dissemination represents a poor prognostic indicator in gastric cancer. Despite a comprehensive molecular characterization of this disease, no peritoneal dissemination-specific signature has been identified, limiting the tailoring of the surgical and oncological treatments. In this review, we outline the available literature focusing on the role of the different molecular pathways involved in the acquisition of peritoneal metastatic dissemination.

Summary: According to our results, several molecular determinants are associated with peritoneal carcinomatosis and are involved in several cellular and molecular carcinogenetic processes. However, a comprehensive understanding of the complex molecular landscape of gastric carcinosis is still lacking.

Key messages: More efforts should be made toward the integration of molecular and histologic data to perform a risk prediction assessment of peritoneal dissemination based on molecular profiling and histological evaluation.

Background: Helicobacter pylori (H. pylori) is the most common chronic bacterial infection. Treatment effectiveness remains a subject of debate considering bacterial antimicrobial resistance. Our aim was to analyze the diagnostic methods and eradication treatments for H. pylori infection in Serbia.

Methods: An observational multicenter prospective study was conducted in Serbia, as part of the European Registry on H. pylori Management (Hp-EuReg). Demographics, treatment indication, diagnostic methods, previous eradication attempts, and treatment were collected at AEG-REDCap e-CRF. Modified intention-to-treat (mITT) and per-protocol (PP) effectiveness analyses were performed. Safety, compliance, and bacterial antimicrobial resistance rates were reported. Data were quality checked.

Results: Overall, 283 patients were included, with a mean age of 55 ± 15 years. Dyspepsia (n = 214, 77%) was the most frequent treatment indication, and histology (n = 144, 51%) was the most used diagnostic method. Overall eradication rate was 95% (PP) and 94% (mITT). Most prevalent first-line therapy was quadruple PPI + clarithromycin + amoxicillin + metronidazole, with a 96% effectiveness (p < 0.001). Second-line main treatment choice was triple amoxicillin + levofloxacin, with a 95% effectiveness (p < 0.05). Single-capsule Pylera® was the most prescribed third-line therapy, with 100% effectiveness (p < 0.05). Longer treatment duration was associated with a higher eradication rate in first-line therapy (p < 0.05). Clarithromycin and quinolone resistance rates in first-line were 24% and 8.3%, respectively. The overall adverse events' incidence rate was 13.4%, and therapy compliance was 97%.

Conclusions: Considering the high eradication rate, 14-day non-bismuth quadruple concomitant therapy is a reasonable first-line choice, while quinolone-based therapy and single-capsule Pylera® should be considered as rescue therapy options.

Background: Alcoholic liver disease (ALD) is still increasing and leads to acute liver injury but also liver cirrhosis and subsequent complications such as liver failure or hepatocellular carcinoma (HCC). As most patients fail to achieve alcohol abstinence, it is essential to identify alternative treatment options in order to improve the outcome of ALD patients.

Methods: Evaluating two large cohorts of patients with ALD from the USA and Korea with a total of 12,006 patients, we investigated the effect on survival of aspirin, metformin, metoprolol, dopamine, and dobutamine drugs in patients with ALD between 2000 and 2020. Patient data were obtained through the "The Observational Health Data Sciences and Informatics consortium," an open-source, multi-stakeholder, and interdisciplinary collaborative effort.

Results: The use of aspirin (p = 0.000, p = 0.000), metoprolol (p = 0.002, p = 0.000), and metformin (p = 0.000, p = 0.000) confers a survival benefit for both AUSOM- and NY-treated cohorts. Need of catecholamines dobutamine (p = 0.000, p = 0.000) and dopamine (p = 0.000, p = 0.000) was strongly indicative of poor survival. β-Blocker treatment with metoprolol (p = 0.128, p = 0.196) or carvedilol (p = 0.520, p = 0.679) was not shown to be protective in any of the female subgroups.

Conclusion: Overall, our data fill a large gap in long-term, real-world data on patients with ALD, confirming an impact of metformin, acetylsalicylic acid, and β-blockers on ALD patient's survival. However, gender and ethnic background lead to diverse efficacy in those patients.

Background: Non-alcoholic fatty liver disease (NAFLD) is caused by ectopic fat accumulation in the liver as a consequence of metabolic perturbations associated with obesity, type 2 diabetes, dyslipidemia, and insulin resistance. People with NAFLD may develop metabolic and cardiovascular complications and/or liver-related complications, especially fibrosis and hepatocellular carcinoma, associated with high morbidity and mortality. Due to the high and increasing prevalence of NAFLD, there is an urgent need to identify people at risk of developing liver fibrosis and complications. CC-chemokine ligand 2 (CCL2) is chemokine that attracts inflammatory monocytes to stressed or injured tissues. Infiltrating inflammatory monocytes and CCL2 are strongly implicated in the pathogenesis of liver disease in animal models; however, evidence in patient cohorts is conflicting.

Methods: We investigated associations between circulating CCL2 and clinical parameters, including fibrosis assessed by liver stiffness measurement, in a cohort of 250 NAFLD patients. We also measured fatty acid binding protein 2 (FABP2), a putative biomarker of intestinal permeability in patients with liver disease, since pro-inflammatory gut-derived microbial products may induce inflammatory chemokines such as CCL2.

Results: Serum CCL2 levels were weakly associated with liver stiffness, but the association was no longer significant after accounting for age, diabetes, and BMI in a multivariable model. Consistent with this, girth and BMI were the strongest predictors of elevated circulating CCL2. Serum FABP2 was weakly, but significantly, correlated with CCL2, and negatively correlated with estimated glomerular filtration rate.

Conclusion: Circulating CCL2 and FABP2 are associated with NAFLD comorbidities but not liver disease progression in patients with NAFLD.

Background: High visceral adipose tissue (VAT) and creeping fat (CrF) in Crohn's disease (CD) have been widely recognized. The VAT to subcutaneous adipose tissue (SAT) ratio and sarcopenia have been associated with CD complications. Studies regarding the influence of body composition predictors on CD complications assessed with magnetic resonance enterography (MRE) are scarce.

Aim: The aim of this study was to assess body composition parameters and CrF in opportunistic MRE as predictors of complicated CD.

Methods: This was a retrospective study of 114 patients with inflammatory (n = 54) and complicated (n = 60) CD. The semiautomated assessment of body composition and the qualitative evaluation of CrF were performed.

Results: Body composition parameters did not differ between both groups regarding the body mass index (p = 0.50), total adipose tissue index (TATI) (p = 0.14), subcutaneous adipose tissue index (SATI) (p = 0.17), visceral adipose tissue index (VATI) (p = 0.33), VAT/SAT ratio (p = 0.77), intramuscular adipose tissue (p = 0.64), skeletal muscle index (p = 0.22), and sarcopenia (p = 0.50). 47 strictures, 18 fistulae, and seven abscesses were identified. Fistulae were more likely to occur in patients with CrF (odds ratio [OR] 5.07, 95% confidence interval [CI] 1.76-14.56; p=<0.001) and high VAT/SAT ratio (OR: 3.82, 95% CI 1.34-10.85; p = 0.01).

Conclusion: Body composition measurements in CD patients displayed no statistically significant difference between the groups of inflammatory and complicated disease. Nonetheless, CD patients stratified in the group of high VAT/SAT ratio and the presence of CrF should be recognized as risk groups for the occurrence of fistulae.

Background: This study aimed to investigate the prognosis of Chinese patients with esophageal squamous cell carcinoma (ESCC) after surgery and its correlation with genomic alterations (GAs) to identify potential prognostic markers.

Methods: The clinical information, pathological specimens, and follow-up information of 50 patients with stage II and III primary ESCC who were surgically resected in the Fourth Hospital of Hebei Medical University from January 2011 to December 2015 were collected in the present study. Based on overall survival (OS), these patients were divided into the short OS group (<3 years) and the long OS group (>4 years). GA detection was performed in patients with ESCC using next-generation sequencing. All categories of GAs were evaluated; the landscape of GAs in patients with ESCC was mapped; and the correlations between clinical characteristics, prognosis, and GAs were analyzed.

Results: There was no skew in the distribution of gender, smoking, and adjuvant therapy between the long OS group and the short OS group. A total of 372 GAs were detected in the 50 patients with ESCC, with 7 types of GAs, including insertions, deletions, and copy number variations, and missense mutations occurred most frequently, with a frequency of >50.0%. Tumor protein 53 (TP53; 50/50, 100%) was the most commonly mutated gene in the entire cohort followed by cyclin D1, cyclin-dependent kinase inhibitor 2A (CDKN2A), and fibroblast growth factor 19. More CDKN2A loss (p = 0.098) was detected in the short OS group than in the long OS group. The results of the multivariate analysis after adjustment for clinical factors showed a statistically significant difference in the CDKN2A loss between the two groups. Data obtained from The Cancer Genome Atlas for surgical ESCC revealed that the CDKN2A loss may be responsible for the poorer prognosis in postoperative patients with ESCC.

Conclusion: In patients with progressive primary ESCC, the poor postoperative prognosis may be epiphenomenally associated with the CDKN2A loss.