Gut and Liver最新文献

Autoimmune pancreatitis (AIP), which is considered the pancreatic expression of a systemic immunoglobulin G4-related disease, is characterized by excessive infiltration of plasmacytes bearing immunoglobulin G4 and a unique form of fibrosis in multiple organs. This relatively new disease entity has garnered great attention from clinicians, but its pathophysiology remains poorly understood. Recent discoveries indicate that plasmacytoid dendritic cell activation followed by robust production of type I interferon and interleukin-33 plays a key role in driving chronic fibro-inflammatory responses in both murine and human AIP. Furthermore, the compositional alterations in the gut microbiota, known as intestinal dysbiosis, triggered plasmacytoid dendritic cell-driven pathogenic type I interferon responses. Intestinal dysbiosis is associated with a breakdown in intestinal barrier function; thus, we examined whether the latter condition affects the development of experimental AIP. Our recent research has revealed that intestinal barrier disruption worsens experimental AIP by facilitating the translocation of pathogenic bacteria, such as Staphylococcus sciuri, to the pancreas from the gut. These results indicate the "gut-pancreas axis" underlies the immunopathogenesis of AIP, and the maintenance of intestinal barrier integrity can prevent the worsening of AIP by inhibiting pancreatic colonization by harmful gut bacteria. In this mini review, the interactions between AIP development and gut microbiota are discussed with the aim of providing useful information not only for researchers but also for clinicians.

Liver tissue-resident memory T (T_RM) cells play a pivotal role in hepatic immune responses. Their unique residence within liver sinusoids allow continuous antigen surveillance. In this review, we highlight the role of liver T_RM cells in protective immunity and disease pathology. Comparisons between human and murine liver T_RM cells reveal species-specific characteristics, suggesting the need for human-focused studies. One key finding is the involvement of liver T_RM cells in viral hepatitis, where they can both control infection and contribute to liver damage. Liver T_RM cells also exhibit dual roles in metabolic-associated steatotic liver disease, promoting inflammation and fibrosis while also contributing to fibrosis resolution. In autoimmune liver diseases, such as autoimmune hepatitis and primary sclerosing cholangitis, the presence of liver T_RM cells correlates with disease severity. In this review, we underscore the importance of liver T_RM cells in vaccine development, particularly vaccines against malaria. Future research should focus on the mechanisms governing T_RM-cell formation, maintenance, and function, with the aim of supporting their protective roles while mitigating detrimental effects. Advancing our understanding of liver T_RM cells will enhance our knowledge of liver immunology and inform novel therapeutic strategies for liver disease management.

Pyloric dysfunction is defined as hypertonia or spasm of the pyloric sphincter. The pylorus plays a key role in gastric emptying, but its function remains incompletely understood. Most studies have focused on gastroparesis regardless of the underlying pathophysiology. Few studies have reported pyloric dysfunction in patients with gastroparesis, and the diagnostic and treatment modalities for pyloric dysfunction are not well established. Recently developed diagnostic modalities assessing pyloric function, such as high-resolution antroduodenal manometry and endoluminal functional lumen imaging, are currently being evaluated. A variety of therapeutic interventions targeting the pylorus, including pharmacologic agents, intrapyloric botulinum injection, endoscopic balloon dilation, stent insertion, surgical pyloroplasty, and gastric peroral endoscopic pyloromyotomy, have been proposed. Among these, gastric peroral endoscopic pyloromyotomy has emerged as a novel, minimally invasive therapy with demonstrated efficacy and safety for refractory gastroparesis. This article reviews the pathophysiology of pyloric dysfunction and the potential diagnostic and therapeutic modalities based on the latest literature.

Background/aims: The prognostic value of serial ¹⁸F-fluorodeoxyglucose positron emission tomography/ computed tomography (¹⁸F-FDG PET/CT) for patients with borderline resectable or locally advanced pancreatic cancer who undergo conversion surgery or continue chemotherapy without surgery has not been well-established.

Methods: A retrospective analysis of patients with pancreatic ductal adenocarcinoma was conducted at Seoul National University Bundang Hospital between March 2013 and February 2022. Patients underwent PET/CT at baseline and subsequent radiologic evaluations following chemotherapy. Changes in the maximum standardized uptake value (SUVmax), mean standardized uptake value (SUVmean), metabolic tumor volume, and total lesion glycolysis were analyzed. Based on their treatment regimens, patients were stratified into the conversion surgery group or nonconversion surgery group. Survival outcomes and various clinical factors were assessed.

Results: Among 121 patients, 52 underwent conversion surgery, and 69 continued to receive chemotherapy without surgery. A significant reduction in the SUVmax was correlated with prolonged recurrence-free survival and overall survival in the conversion surgery group. Confirmation of a pathologic response indicated a significant association between reductions in the SUVmax and positive outcomes. Reductions in the metabolic tumor volume and total lesion glycolysis were associated with improved progression-free survival and overall survival in the nonconversion surgery group.

Conclusions: Serial PET/CT scans demonstrated prognostic value in pancreatic ductal adenocarcinoma patients, revealing distinct correlations in the conversion surgery group and nonconversion surgery group.

Background/aims: To construct a new model based on folate receptor-positive circulating tumor cells (FR⁺-CTC) for the preoperative prediction of peritoneal metastasis in gastrointestinal malignancies and to apply this model in clinical practice.

Methods: Patients with gastrointestinal malignancies who had undergone preoperative FR⁺-CTC counts were retrospectively collected. Risk factors for peritoneal metastasis in patients with gastrointestinal malignancies were identified using a logistic regression model. The "pROC" package in R software was employed to plot the receiver operating characteristic curve for predicting peritoneal metastasis in these patients based on identified risk factors. Spearman correlation analysis was performed to assess the relationship between FR⁺-CTC counts and risk factors.

Results: A total of 396 patients meeting the inclusion criteria were finally included in the study. The number of FR⁺-CTC, albumin level, total protein level, and cancer antigen 125 (CA-125) level were identified as risk factors affecting peritoneal metastasis in gastrointestinal malignancies. The number of FR⁺-CTC was significantly negatively correlated with albumin (R=-0.21, p<0.001), and total protein levels (R=-0.10, p=0.047), and a positively correlated with CA-125 level (R=0.15, p=0.004). The number of FR⁺-CTCs was significantly higher in patients with peritoneal metastasis, lymph node metastasis, vascular invasion, neural invasion, and in those with stage T3-4 and III-IV gastrointestinal malignancies (p<0.05 for all). The model demonstrated stable predictive capacity, as validated through 10-fold cross-validation.

Conclusions: FR⁺-CTCs can serve as a novel biomarker for gastrointestinal malignancies. A new model based on FR⁺-CTCs demonstrated strong predictive capabilities for the preoperative assessment of peritoneal metastasis in gastrointestinal cancers.

Background/aims: Clinical data on the efficacy and safety of the dual delayed-release formulation of 10-mg esomeprazole (HIP2101) are currently limited. Therefore, this study compared the efficacy and safety of HIP2101 and 20-mg famotidine (RLD2101) in patients with gastric erosions.

Methods: In this multicenter, randomized, double-blind, active-control, phase III study, 326 patients with endoscopically proven gastric mucosal erosion were randomly assigned to receive either HIP2101 or RLD2101 once daily for 2 weeks. The primary endpoint was the rate of improvement of erosion. Secondary endpoints (rate of cure of erosion and edema, and rate of improvement of hematin and gastrointestinal symptoms) and treatment-emergent adverse events were compared between the groups.

Results: Based on the per-protocol set (PPS) analysis, the improvement rates for erosion were 64.9% (98/151) and 63.7% (100/157) in the HIP2101 and RLD2101 groups, respectively (95% confidence interval, -9.5 to 11.9). The lower bound of the 95% confidence interval was greater than the noninferiority margin of -14%. These results were similar to those of the full analysis set (FAS) (HIP2101 group, 64.6%; RLD2101 group, 62.7%). Based on the PPS and FAS analyses, the cure rates for erosion and edema and the improvement rates for hematin and gastrointestinal symptoms were comparable between the groups. The number of adverse events did not differ significantly between the groups.

Conclusions: The efficacy and safety of HIP2101 were comparable to those of RLD2101 in the treatment of gastric erosions and symptomatic improvement. These findings suggest that HIP2101 may be a novel treatment option for gastritis (ClinicalTrials.gov identifier: NCT05024721).

Background/aims: Autoimmune gastritis (AIG) is an immune-mediated chronic atrophic gastritis. This study aimed to investigate the clinical characteristics of AIG patients, stratified by age, sex, and the presence/absence of autoimmune thyroid disease (AITD).

Methods: We reviewed the data of AIG patients treated at a large academic tertiary teaching hospital from January 2018 to October 2023. Patients were grouped according to age (≥60 years or younger), sex, and the presence/absence of AITD and the clinical characteristics of the groups were analyzed.

Results: This study included 183 AIG patients. Older patients (≥60 years) had higher rates of pernicious anemia (26.7% vs 11.8%) and intrinsic factor antibodies (36.8% vs 20.9%) than younger patients (<60 years). However, no significant differences were observed in the extent of gastric atrophy, sex ratio, or serum gastrin levels between the age groups. Female patients were more prone than males to exhibit enterochromaffin-like cell hyperplasia (69.4% vs 39.2%) and had a higher prevalence of iron deficiency anemia (IDA) (25.0% vs 0.0%, p=0.004). AIG patients with AITD were younger (50.9±12.0 years vs 58.0±11.5 years), were more likely to be females (p=0.023), and exhibited milder gastric body atrophy (p=0.009) than those without AITD.

Conclusions: AIG patients demonstrate age- and sex-related differences in clinical characteristics. Older patients are more likely to have intrinsic factor antibody positivity and pernicious anemia, while women are more prone to IDA. There is a high comorbidity rate between AITD and AIG, and patients with AITD-associated AIG are typically younger and tend to have milder gastric body atrophy.

Background/aims: The aim of this study was to investigate the effect of a surgical treatment algorithm recently proposed by the American Association for the Study of Liver Diseases (AASLD) on survival outcomes in patients with early-stage hepatocellular carcinoma (HCC) and identify effective alternative treatment modalities when liver transplantation (LT) is not available.

Methods: We studied the clinical data of 1,442 patients who were diagnosed with early-stage HCC (a single lesion measuring 2-5 cm in size or 2 to 3 lesions measuring ≤3 cm in size) between 2013 and 2018 and classified as Child-Turcotte-Pugh (CTP) A or B. Analyses were separately performed for individuals recommended for resection (single lesion, CTP A and no clinically significant portal hypertension) and those recommended for LT (single lesion with impaired liver function such as CTP B or clinically significant portal hypertension or multiple lesions).

Results: Of 791 patients recommended for surgical resection, 85.8% underwent resection. The 5-year survival rate was higher for patients who underwent surgical resection than for those who received other treatments (89.4% vs 72.3%). Among 651 patients recommended for LT, only 3.4% underwent the procedure. The most common alternative treatment modalities were transarterial therapy (39.3%) followed by resection (28.9%) and ablation (27.8%). The overall survival rate associated with transarterial therapy was lower than that for resection and ablation, whereas that of the latter two treatments were comparable.

Conclusions: The survival outcomes of treatment strategies that most closely aligned with the algorithm proposed by the AASLD were superior to those of alternative treatment approaches. However, LT in patients with early-stage HCC can be challenging. When LT is not feasible, resection and ablation can be considered first-line alternative options.

Background/aims: Small bowel capsule endoscopy (SBCE) has become the standard for initial evaluation in the diagnosis of small bowel lesions. Although optimal visualization of the mucosa is important, patients experience difficulty in consuming a large volume of bowel preparation agents. This study aimed to compare the efficacy and safety of 1-L polyethylene glycol (PEG) with ascorbic acid (AA) and 2-L PEG with AA.

Methods: In this prospective, multicenter, non-inferiority study, patients who received SBCE were randomly assigned to consume 1-L PEG with AA or 2-L PEG with AA for small bowel preparation. The primary outcome was adequate small bowel visibility quality (SBVQ). The secondary outcomes included diagnostic yield, cecal complete rate, and adverse events.

Results: One hundred and forty patients were enrolled in this study, 70 patients per group. In the per-protocol analysis, there were no significant differences in the adequate SBVQ rate (94.0% vs 94.3%; risk difference, -0.3; 95% confidence interval, -8.1 to 7.6; p=1.000), diagnostic yield rate (49.3% vs 48.6%, p=0.936), or cecal complete rate (88.1% vs 92.9%, p=0.338) between the 1-L PEG with AA group and 2-L PEG with AA group. The incidence of adverse events did not differ significantly between the groups (12.9% vs 11.9%, p=0.871).

Conclusions: One liter-PEG with AA is not inferior to 2-L PEG with AA in terms of adequate SBVQ for SBCE. One liter-PEG with AA can be recommended as the standard method for bowel cleansing for SBCE.

Background/aims: Early colorectal cancer (ECC) is commonly resected endoscopically. Perforation is a devastating complication of endoscopic resection. We aimed to identify the characteristics and predictive risk factors for perforation related to endoscopic resection of ECC.

Methods: This nationwide retrospective multicenter study included patients with ECC who underwent endoscopic resection. We investigated the demographics, endoscopic findings at the time of treatment, and histopathological characteristics of the resected specimens. Logistic regression analysis was used to investigate the clinical factors associated with procedure-related perforations. Survival analysis was conducted to assess the impact of perforation on the overall survival of patients with ECC.

Results: This study included 965 participants with a mean age of 63.4 years. The most common endoscopic treatment was conventional endoscopic mucosal resection (n=573, 59.4%), followed by conventional endoscopic submucosal dissection (n=259, 26.8%). Thirty-three patients (3.4%) experienced perforations, most of which were managed endoscopically (n=23/33, 69.7%). Patients who undergo endoscopic submucosal dissection-hybrid and precut endoscopic mucosal resection have a higher risk of perforation than those who undergo conventional endoscopic mucosal resection (odds ratio, 78.65 and 39.72, p<0.05). Procedure-related perforations were not associated with patient survival.

Conclusions: Perforation after endoscopic resection had no significant impact on the prognosis of ECC. The type of endoscopic resection was a crucial predictor of perforation. Large-scale prospective studies are needed to further investigate endoscopic resection of ECC.