Digestion最新文献

Background: Drug-induced autoimmune hepatitis (DI-AIH) has been proposed as a distinct phenotype of drug-induced liver injury (DILI), and frequently has been associated with specific drugs, such as minocycline and nitrofurantoin. However, no clear definition of DI-AIH has been established thus far.

Objectives: We aimed to identify features distinguishing DI-AIH from DILI and idiopathic autoimmune hepatitis (AIH) in an attempt to further define a DI-AIH phenotype.

Method: A cohort of 38 previously reported DILI and AIH patients who were prospectively recruited at our tertiary centre and who received corticosteroid was analysed regarding the phenotypical presentation and outcome of DI-AIH, DILI, and AIH.

Results: AIH (n = 19), DILI (n = 8), and DI-AIH (n = 11) patients presented with similar clinical features at onset, with the only difference being a higher Roussel Uclaf Causality Assessment Method (RUCAM) score in the DILI and DI-AIH patients. Post-treatment AIH scores were lower and a more rapid decrease of alanine aminotransferase in the first week of corticosteroid treatment was observed in both DILI groups when compared to AIH patients, while no significant differences were observed between DI-AIH and DILI patients. Relapse occurred in DI-AIH but not in DILI patients (36% vs. 0%) with a more frequent need for long-term immunosuppression (27% vs. 13%).

Conclusions: Our data show that relapse after cessation of corticosteroids and need for further immunosuppressive treatment does occur in a substantial proportion of DI-AIH patients. However, no other phenotypical differences between DILI due to agents commonly associated with DI-AIH and DILI due to other drugs were identified.

Introduction: Saliva secretion is significantly lower in patients with mild reflux esophagitis than in healthy controls. A previous study on healthy controls showed that stimulated saliva secretion was lower in females than in males. Saliva secretion may be lower in female patients with mild reflux esophagitis than in male patients. Therefore, the present study investigated sex differences in saliva secretion in patients with mild reflux esophagitis.

Methods: Twenty-five male patients with mild reflux esophagitis, 25 male healthy controls, 24 female patients with mild reflux esophagitis, and 24 female healthy controls were recruited for this case-control study. Saliva secretion was assessed as follows: each patient chewed sugar-free gum for 3 minutes prior to endoscopy, and the volume and pH of saliva before and after acid loading as an index of the acid-buffering capacity were measured.

Results: No significant differences were observed in the amount of stimulated saliva secretion, salivary pH, or the acid-buffering capacity between male patients with mild reflux esophagitis and healthy controls. No significant differences were noted in salivary pH between female patients with mild reflux esophagitis and healthy controls; however, the amount of stimulated saliva secretion was significantly lower (p = 0.0023) in the former (2.5 [1.9-4.1]) than in the latter (4.6 [3.2-6.6]), while the acid-buffering capacity was slightly lower (p = 0.0578) in the former (5.9 [5.7-6.2]) than in the latter (6.2 [6.0-6.5]).

Conclusion: The amount of stimulated saliva secretion was significantly lower in female patients with mild reflux esophagitis than in female healthy controls. This reduction in saliva secretion may affect the pathophysiology of mild reflux esophagitis in females.

Introduction: Regorafenib is a multi-kinase inhibitor approved for patients with metastatic colorectal cancer (mCRC) who were previously treated with standard therapies. A few reports showed the impact of KRAS mutation on therapeutic efficacy of regorafenib. Only one study reported poor prognoses for patients treated with regorafenib who had large amounts of circulating cell-free DNA (cfDNA). In the present study, we evaluated the impact of KRAS mutations in tissue or plasma and amounts of cfDNA on prognoses of mCRC patients treated with regorafenib.

Method: This is a biomarker investigation of the RECC study, which evaluated efficacy of regorafenib dose-escalation therapy. Plasma samples were obtained just before initiation of treatment with regorafenib. KRAS mutations were evaluated using tissue and plasma samples. cfDNA was extracted from plasma samples and quantified.

Results: Forty-five patients were enrolled in this biomarker study. Median progression-free survival (PFS) and overall survival (OS) of patients without KRAS mutations in tissues were 1.9 months (95% confidence interval [CI] 1.7-2.0) and 8.9 months (95% CI: 6.5-11.2), and those of patients with KRAS mutations were 1.4 months (95% CI: 1.3-1.5) and 6.8 months (95% CI: 5.0-8.5). Median PFS and OS of patients with plasma KRAS mutations were 1.9 months (95% CI: 1.8-1.9) and 7.0 months (95% CI: 5.3-8.7), respectively. Median PFS and OS of patients without plasma KRAS mutations were 1.7 months (95% CI: 1.1-2.3) and 8.9 months (95% CI: 6.7-11.2), respectively. Prior to administration of regorafenib, KRAS mutations were detected in 6 of 16 (37.5%) patients who had no tissue KRAS mutations. Median OS of patients with high cfDNA concentration (>median) was significantly poorer than that of patients with low cfDNA.

Conclusion: KRAS mutations in the tissue or plasma have no impact on efficacy of regorafenib. KRAS emerging mutations were observed in quite a few patients. Large amounts of cfDNA may indicate poorer prognoses for patients receiving late-line regorafenib chemotherapy.

Introduction: Aortic stenosis (AS) is sometimes associated with gastrointestinal bleeding, and this phenomenon is known as Heyde's syndrome. Such bleeding is most often considered to originate from gastrointestinal angiodysplasias, but the frequency and endoscopic features of such bleeding remain unclear. This study aimed to determine the frequency and endoscopic features of gastrointestinal angiodysplasia in patients with severe AS.

Patients and methods: In this multicenter, retrospective study, we evaluated consecutive patients who underwent transcatheter aortic valve implantation (TAVI) with severe AS from May 2016 to December 2019. We extracted the data on the clinicopathological features according to the status of anemia, the proportion of patients who underwent gastrointestinal endoscopic examinations and demonstrated gastrointestinal angiodysplasia, and identified the endoscopic features associated with such patients.

Results: In 325 patients, the rates of moderate/severe anemia (hemoglobin < 11 g/dL) were 52%. Regarding medicine, there were no significant differences between the patients with and without moderate/severe anemia. Patients were examined by esophagogastroduodenoscopy (21%), colonoscopy (12%), and balloon-assisted enteroscopy or small bowel capsule endoscopy (1.5%). Patients with moderate/severe anemia had significantly more angiodysplasia (38.3% vs. 7.7%; p < 0.0001) and active bleeding (23.4% vs. 0%; p < 0.01). Angiodysplasia was detected in 21 patients (stomach, n = 9; small intestine, n = 5, and colon, n = 10).

Conclusions: The results suggest, for the first time, that patients with severe AS who underwent TAVI and moderate/severe anemia frequently had gastrointestinal angiodysplasia and active bleeding throughout the entire gastrointestinal tract.

Introduction: Endoscopic full-thickness resection (EFTR) without laparoscopic assistance (pure EFTR) is an emerging, less invasive treatment for gastrointestinal stromal tumors (GISTs). However, the technique has seldom been performed outside China because of concerns regarding pneumoperitoneum, maintenance of endoscopic view, and endoscopic suturing. This study aimed to evaluate the efficacy and safety of endoscopic resection with one-port placement (EROPP) for gastric GISTs.

Methods: This retrospective study included 17 patients with gastric GISTs originating from the muscularis propria who underwent EROPP between 2019 and 2022. One camera port was inserted in the umbilicus before initiating the endoscopic procedure to maintain intra-abdominal pressure, which was monitored and adjusted via this port. While allowing for conversion to laparoscopic surgery if needed, EFTR was performed as follows: (1) circumferential incision of the mucosal and submucosal layers around the lesion was performed by typical endoscopic submucosal dissection; (2) an intentional perforation and subsequent seromuscular resection was made using dental floss and an endo-clip for traction; and (3) closure of the gastric full-thickness defect was performed with an over-the-scope clip (OTSC) after peroral retrieval of the specimen. We retrospectively assessed the short-term outcomes and safety.

Results: All procedures were completed successfully without conversion to laparoscopic surgery. The median size of the resected tumors was 23 mm (range, 8-35 mm), the median resection time was 36 min (range, 22-95 min), and closure time was 18 min (range, 10-45 min). The rates of en bloc and complete resection were 100% and 88%, respectively. In 2 cases, another port was added to aspirate the leaking fluid or check the condition of the endoscopic closure. All gastric defects were endoscopically closed, mainly using OTSCs. The recovery course for all patients was uneventful, and no adverse events were reported.

Conclusions: EROPP is a safe and minimally invasive treatment for gastric GISTs and appears to be suitable for introducing EFTR procedures.

Background: The STRIDE-II position statement has established endoscopic healing as the long-term target of treatment for inflammatory bowel disease, and ileocolonoscopy is considered the gold standard for assessment of endoscopic healing. However, precise assessment of endoscopic healing cannot be achieved by ileocolonoscopy alone in patients with Crohn's disease (CD).

Summary: Approximately 70-80% of patients with CD have small bowel disease, and intestinal complications develop more frequently in the small bowel than in the colorectum. The recent advent of small bowel capsule endoscopy and balloon-assisted enteroscopy has not only clarified the higher incidence of proximal small bowel lesions but has also revealed the presence of such lesions as a possible risk factor for poor disease outcomes. Evidence has shown that the therapeutic efficacy of biologics may differ between the small bowel and the colorectum. In the postoperative setting, it was recently recognized that intestinal lesions other than those at the anastomotic site should be carefully monitored considering the risk of postoperative recurrence. However, there are some obstacles to implementing endoscopic assessment of the entire small bowel and colorectum. Inflammatory biomarkers might play important roles in such scenarios, but the predictive value of biomarkers for small bowel endoscopic healing remains controversial.

Key messages: Endoscopic assessment of the small bowel is indispensable for improvement of the long-term outcome of CD. The validity of endoscopic healing and transmural healing as long-term targets remains to be fully elucidated.

Introduction: Vonoprazan, a novel potassium-competitive acid blocker, has a strong acid suppression effect and potent efficacy in acid-associated diseases, including Helicobacter pylori eradication. We performed a systematic review and meta-analysis to investigate the efficacy and safety of vonoprazan/amoxicillin dual therapy for H. pylori eradication.

Methods: We conducted a systematic literature search through PubMed, Web of Science, EMBASE, and the Cochrane Library up to June 2022, to identify randomized controlled trials and cohort studies comparing vonoprazan/amoxicillin dual therapy and triple therapies for H. pylori eradication. Primary outcomes were cure rates and relative efficacy. Secondary outcomes included adverse events, dropout rate, and subgroup analysis.

Results: Five studies with 1,852 patients were included in the analysis. The cure rates of vonoprazan/amoxicillin dual therapy were 85.6% with 95% confidence interval (CI) of 79.7-91.5% and 88.5% (95% CI: 83.2-93.8%) in the intention-to-treat and per-protocol analyses. The efficacy of vonoprazan/amoxicillin dual therapy was not inferior to that of triple therapy with pooled risk ratio (RR) of 1.03 (95% CI: 0.97-1.10) and 1.02 (95% CI: 0.98-1.08) in intention-to-treat and per-protocol analyses; while it was significantly superior to the omeprazole or lansoprazole-based triple therapy (RR = 1.15, 95% CI: 1.05-1.25, p = 0.001). For clarithromycin-resistant strains, vonoprazan/amoxicillin dual therapy showed superiority to vonoprazan-based triple therapy (86.7% vs. 71.4%, RR = 1.20, 95% CI: 1.03-1.39, p = 0.02); however, vonoprazan/amoxicillin dual therapy was significant inferior to vonoprazan-based triple therapy for clarithromycin-sensitive strains (83.0% vs. 92.8%, RR = 0.90, 95% CI: 0.85-0.95, p = 0.0002). The adverse effects of vonoprazan/amoxicillin dual therapy were lower than those of triple therapy (21.2% vs. 26.5%, RR = 0.86, 95% CI: 0.73-1.01, p = 0.06), especially the incidence of diarrhea (p = 0.01).

Conclusions: The efficacy of vonoprazan/amoxicillin dual therapy is noninferior to vonoprazan-based triple therapy but superior to the omeprazole or lansoprazole-based triple therapy and has less side effects. Patients with clarithromycin-resistant strains are particularly expected to benefit from vonoprazan/amoxicillin dual therapy.

Background: The genetic background of inflammatory bowel diseases (IBDs) has been explored using genetic analysis techniques, such as genome-wide association studies for the population and whole-exome sequencing analyses of family lineages in cases of very early onset.

Summary: The results of genetic analysis for IBD indicated the involvement of innate and adaptive immune system variations and epithelial abnormalities in the pathogenesis of IBD. Several associated genes were also reported, indicating that IBD occurs in a heterogeneous population with an extremely diverse background. The genetic background of IBDs is currently being studied to understand not only its onset but also its prognosis, response to treatment, and adverse effects. In the future, it will be possible to use an individual's genetic information for determining appropriate treatment. In Japan, the NUDT15 polymorphism test is performed before administering thiopurine preparations. However, because of racial differences in genetic analysis, biased analysis toward some racial groups may result in overlooking important genetic backgrounds of IBD.

Key message: Studies of IBDs in a more diverse range of races are expected to elucidate genetic factors through a transethnic analysis, thereby aiding the development of novel treatments and precision medicine for IBDs.

Background: Mucosal healing (MH) is recognized as a therapeutic target in ulcerative colitis (UC) because of evidence that it is associated with favorable clinical outcomes. Current endoscopic assessment of MH by conventional white-light endoscopy is subject to several important clinical issues including the subjective nature of assessment, intra- and interobserver variability, and persistent microscopic inflammation, even in mucosa it was observed as quiescent on conventional endoscopy.

Summary: Advances in image-enhancement technologies enable the provision of high-contrast images that emphasize the mucosal structures, blood vessel patterns, and color tones of the intestinal mucosa, and recently, several image-enhanced endoscopy (IEE) techniques have become available for the assessment of MH in UC. Narrow-band imaging and dual-red imaging facilitate visualization of mucosal vascular structures, which is useful for detecting minor inflammation and predicting relapse because of the capturing of information on incomplete vascular regeneration in patients with UC. Linked-color imaging (LCI) is optimized to emphasize the redness of the mucosa and blood vessels, and is superior for depicting subtle color changes arising from mucosal inflammation. LCI could possibly be used to stratify UC patients with MH on conventional endoscopy. Autofluorescence imaging and i-scan can also depict subtle histological changes underlying the healing of mucosa in UC, revealing them as simple color changes.

Key messages: Accumulating evidence suggests that IEE techniques could overcome current unmet needs in the endoscopic assessment of MH in UC and contribute to improving therapy based on treat-to-target strategies.