Life-threatening gastrointestinal bleeding caused by perforation of a penetrating atherosclerotic ulcer into the esophagus.

We present a case of life-threatening gastrointestinal bleeding caused by a penetrating atherosclerotic ulcer (PAU) that ruptured into the esophagus. A 65-year-old man presented with pyrexia and nausea. Contrast-enhanced computed tomography (CT) performed on admission revealed a hematoma between the lower esophagus and descending aorta due to a contained rupture of a PAU, which was undiagnosed at that time. Esophagogastroduodenoscopy (EGD) performed on the fifth day of admission revealed a subepithelial lesion in the lower esophagus, further complicated by ulcer formation. Biopsy did not reveal any malignant findings. On the eighth day of admission, the patient experienced substantial hematemesis with vital signs indicative of shock. Emergency EGD was performed, which revealed life-threatening bleeding in the lower esophagus. Contrast-enhanced CT revealed an aortoesophageal fistula with massive hematemesis, after which the patient died. An autopsy revealed perforation of the PAU into the esophagus without aortic dissection or a true aneurysm.Patients with atherosclerosis who develop recent-onset gastrointestinal symptoms, progressive anemia, and/or periaortic lesions should be carefully evaluated using contrast-enhanced CT, and PAU should be considered in the differential diagnosis.

Percutaneous transhepatic obliteration of a large portosystemic shunt associated with hepatic encephalopathy using a technique of n-butyl-2-cyanoacrylate injection inside hydrogel-coated coils: A case report.

Portosystemic shunts with cirrhosis may lead to hepatic encephalopathy (HE), which is often pharmacotherapy-resistant. We report a case of a 66-year-old female patient diagnosed with alcoholic cirrhosis and uncontrolled HE. She underwent percutaneous transhepatic obliteration (PTO) for treatment of a large portosystemic shunt from the left and right gastric veins to the azygos vein. We embolized the target veins using hydro-coated coils and filled them with n-butyl-2-cyanoacrylate (NBCA), leading to firmed obstruction of the large portosystemic shunt without NBCA migration, thus reducing the number of coils required. The HE symptoms improved after PTO and could thereafter be controlled with conservative therapy. Our results showed that PTO using an NBCA injection inside hydrogel-coated coils for a large portosystemic shunt associated with HE is effective and safe.

A case of early gastric cancer resembling a subepithelial lesion diagnosed by endoscopic ultrasound-guided fine needle aspiration.

We present a case of early gastric cancer resembling a subepithelial lesion (GCSEL) derived from the submucosal ectopic gastric glands (SEGGs), diagnosed using endoscopic ultrasound-guided fine needle aspiration (EUS-FNA). A 55-year-old woman was referred to our hospital for the investigation of a subepithelial lesion (SEL). Contrast computed tomography and esophagogastroduodenoscopy revealed two SELs in the greater curvature of the fundus and the posterior wall of the upper body of the stomach. EUS revealed a hypoechoic lesion in the submucosa and suggested partial invasion into the muscularis propria of the greater curvature of the fundus, and an anechoic lesion in the submucosa of the posterior wall of the upper body. The different diagnosis for the SEL in the fundus was GCSEL, neuroendocrine tumor, malignant lymphoma, and gastric adenocarcinoma of fundic gland type. EUS-FNA findings suggested adenocarcinoma. The patient underwent a laparoscopic proximal gastrectomy. Pathological findings confirmed a differentiated tubular adenocarcinoma derived from the SEGG, which partially invaded into the submucosa of the surrounding gastric wall without lymphovascular invasion or lymph node metastasis. The patient has been recurrence-free after 10 months of follow-up. EUS should be performed for SELs followed by EUS-FNA for lesions, such as GCSEL, that require early intervention.

Relevance of pepsinogen, gastrin, and endoscopic atrophy in the diagnosis of autoimmune gastritis.

Simple objective modalities are required for evaluating suspected autoimmune gastritis (AIG). This cross-sectional study aimed to examine whether pepsinogen, gastrin, and endoscopic findings can predict AIG. The diagnostic performance of endoscopic findings and serology in distinguishing AIG was evaluated. AIG was diagnosed in patients (N = 31) with anti-parietal cell antibody and/or intrinsic factor antibody positivity and histological findings consistent with AIG. Non-AIG patients (N = 301) were seronegative for anti-parietal cell antibodies. Receiver operating characteristic curve analysis of the entire cohort (N = 332) identified an endoscopic atrophic grade cutoff point of O3 on the Kimura-Takemoto classification (area under the curve [AUC]: 0.909), while those of pepsinogen-I, I/II ratio, and gastrin were 20.1 ng/mL (AUC: 0.932), 1.8 (AUC: 0.913), and 355 pg/mL (AUC: 0.912), respectively. In severe atrophy cases (≥ O3, N = 58, AIG/control; 27/31), the cutoff values of pepsinogen-I, I/II ratio, and gastrin were 9.8 ng/mL (AUC: 0.895), 1.8 (AUC: 0.86), and 355 pg/mL (AUC: 0.897), respectively. In conclusion, endoscopic atrophy is a predictor of AIG. High serum gastrin and low pepsinogen-I and I/II ratio are predictors even in the case of severe atrophy, suggesting their usefulness when the diagnosis of AIG is difficult or as serological screening tests.

Acetaldehyde exposure underlies functional defects in monocytes induced by excessive alcohol consumption.

Increased intestinal permeability and hepatic macrophage activation by endotoxins are involved in alcohol-induced liver injury pathogenesis. Long-term alcohol exposure conversely induces endotoxin immune tolerance; however, the precise mechanism and reversibility are unclear. Seventy-two alcohol-dependent patients with alcohol dehydrogenase-1B (ADH1B, rs1229984) and aldehyde dehydrogenase-2 (ALDH2, rs671) gene polymorphisms admitted for alcohol abstinence were enrolled. Blood and fecal samples were collected on admission and 4 weeks after alcohol cessation and were sequentially analyzed. Wild-type and ALDH2*2 transgenic mice were used to examine the effect of acetaldehyde exposure on liver immune responses. The productivity of inflammatory cytokines of peripheral CD14+ monocytes in response to LPS stimulation was significantly suppressed in alcohol dependent patients on admission relative to that in healthy controls, which was partially restored by alcohol abstinence with little impact on the gut microbiota composition. Notably, immune suppression was associated with ALDH2/ADH1B gene polymorphisms, and patients with a combination of ALDH2*1/*2 and ADH1B*2 genotypes, the most acetaldehyde-exposed group, demonstrated a deeply suppressed phenotype, suggesting a direct role of acetaldehyde. In vitro LPS and malondialdehyde-acetaldehyde adducted protein stimulation induced direct cytotoxicity on monocytes derived from healthy controls, and a second LPS stimulation suppressed the inflammatory cytokines production. Consistently, hepatic macrophages of ethanol-administered ALDH2*2 transgenic mice exhibited suppressed inflammatory cytokines production in response to LPS compared to that in wild-type mice, reinforcing the contribution of acetaldehyde to liver macrophage function. These results collectively provide new perspectives on the systemic influence of excessive alcohol consumption based on alcohol-metabolizing enzyme genetic polymorphisms.

Role of CC chemokine receptor 9 in the progression of murine and human non-alcoholic steatohepatitis.

BACKGROUND & AIMS: The number of patients with non-alcoholic steatohepatitis (NASH) is increasing globally. Recently, specific chemokine receptors have garnered interest as therapeutic targets in NASH. This is the first report to examine the role of the C-C chemokine receptor 9 (CCR9)/C-C chemokine receptor ligand 25 (CCL25) axis, and to reveal its therapeutic potential in NASH. METHODS: Patients with biopsy-proven non-alcoholic liver disease (NAFLD) were recruited and their serum and hepatic chemokine expression was examined. Furthermore, wild-type (WT) and Ccr9-/- mice were fed a high-fat high-cholesterol (HFHC) diet for 24 weeks to establish NASH. RESULTS: Serum CCL25, and hepatic CCR9 and CCL25 expression levels were increased in patients with NASH compared to healthy volunteers. Furthermore, Ccr9-/- mice were protected from HFHC diet-induced NASH progression both serologically and histologically. Flow cytometry and immunohistochemistry analysis showed that CCR9+CD11b+ inflammatory macrophages accumulated in the inflamed livers of HFHC diet-fed mice, while the number was reduced in Ccr9-/- mice. Consistent with human NASH livers, CCR9 was also expressed on hepatic stellate cells (HSCs) in mice with NASH, while CCR9-deficient HSCs showed less fibrogenic potential in vitro. Administration of a CCR9 antagonist hampered further fibrosis progression in mice with NASH, supporting its potential clinical application. Finally, we showed that CCR9 blockade attenuated the development of NAFLD-related hepatocellular carcinoma in HF diet-fed mice injected with diethylnitrosamine. CONCLUSIONS: These results highlight the role of the CCR9/CCL25 axis on macrophage recruitment and fibrosis formation in a murine NASH model, providing new insights into therapeutic strategies for NASH. LAY SUMMARY: Herein, we show that a specific chemokine axis involving a receptor (CCR9) and its ligand (CCL25) contributes to the progression of non-alcoholic steatohepatitis and carcinogenesis in humans and mice. Furthermore, treatment with a CCR9 antagonist ameliorates the development of steatohepatitis and holds promise for the treatment of patients with non-alcoholic steatohepatitis.

Stent placement using dual-channel endoscope for biloma after EUS-guided hepaticogastrostomy.

Highlight Nakamura and colleagues report a case of successful stent placement for biloma through a migrated EUS-guided hepaticogastrostomy stent, using a dual-channel endoscope and the hairpin guidewire technique. This method enables biliary drainage as a potential rescue technique for EUS-guided hepaticogastrostomy stent obstruction with a long metallic stent in the stomach.

Efficacy and safety of immediate oral intake in patients with mild acute pancreatitis: A randomized controlled trial.

OBJECTIVES: Early enteral nutrition is recommended for patients with severe acute pancreatitis (AP); however, nutritional management strategies for patients with mild AP have not been established. The aim of this study was to evaluate the benefits and safety of immediate oral intake of low-fat solid food in patients with mild AP who were allowed to take opioid analgesics. METHODS: In this single-center randomized study, the immediate feeding (IMF) group was permitted immediate oral intake of low-fat (15 g/d) solid food. In the standard food (STF) group, patients received gradually increasing amounts of dietary fat. Twenty-six patients were randomized, with 13 allocated to each group. The primary outcome was the period between diagnosis and recovery from AP. The cost and rate of progression to severe disease were evaluated as secondary outcomes. RESULTS: The IMF group (mean recovery days: 2 ± 1) recovered significantly earlier (mean difference in recovery days: 6.3; 95% confidence interval [CI], 4.8-7.9; P < 0.001) than the STF group (mean recovery days: 8.3 ± 2.3), with a lower overall treatment cost (mean difference in costs: -$460; 95% CI, -$880 to -$40; P = 0.034). The IMF group showed a lower rate of progression to severe AP (IMF, 0%; STF, 15.3%; P = 0.48). CONCLUSION: The initial treatment strategy for mild AP should be altered from the gradual introduction of oral feeding upon the absence of pain to immediate oral nutrition with opioid analgesics, to improve treatment efficacy and reduce treatment cost.

Impact of electrical pulse cut mode during endoscopic papillectomy: Pilot randomized clinical trial.

OBJECTIVE: Endoscopic papillectomy is increasingly being used for ampullary adenoma treatment. However, it remains challenging despite increased safety with treatment advances. The ideal power output and electrosurgical current mode for mucosal resection are not established. We aimed to identify the ideal electrical pulse for use during resection. METHODS: This pilot randomized, single-blind, prospective, multicenter trial, recruited patients with ampullary adenomas and conventional anatomy who were scheduled to undergo endoscopic papillectomy. Endoscopic treatment was performed using a standardized algorithm and patients were randomized for endoscopic papillectomy with Endocut or Autocut. The primary outcome was the incidence of delayed bleeding. Incidence of procedure-related pancreatitis, successful complete resection, pathological findings, and other adverse events were secondary endpoints. RESULTS: Sixty patients were enrolled over a 2-year period. The incidences of delayed bleeding (13.3% vs. 16.7%, P = 1.00) and pancreatitis (27% vs. 30%, P = 0.77) were similar between both groups. The rate of crush artifacts was higher in the Endocut than in the Autocut group (27% vs. 3.3%, P = 0.03). Immediate bleeding when resecting tumors greater than 14 mm in diameter was more common in the Autocut than in the Endocut group (88% vs. 46%, P = 0.04). CONCLUSIONS: The Autocut and Endocut modes have similar efficacy and safety for endoscopic papillectomy. The Endocut mode may prevent immediate bleeding in cases with large tumor sizes, although it causes more frequent crush artifacts. REGISTRY AND THE REGISTRATION NUMBER: The Japanese UMIN Clinical Trials Registry (UMIN-CTR: 000021382).

Previous Helicobacter pylori infection-induced atrophic gastritis: A distinct disease entity in an understudied population without a history of eradication.

Individuals with chronic atrophic gastritis who are negative for active H. pylori infection with no history of eradication therapy have been identified in clinical practice. By excluding false-negative and autoimmune gastritis cases, it can be surmised that most of these patients have experienced unintentional eradication of H. pylori after antibiotic treatment for other infectious disease, unreported successful eradication, or H. pylori that spontaneously disappeared. These patients are considered to have previous H. pylori infection-induced atrophic gastritis. In this work, we define these cases based on the following criteria: absence of previous H. pylori eradication; atrophic changes on endoscopy or histologic confirmation of glandular atrophy; negative for a current H. pylori infection diagnosed in the absence of proton-pump inhibitors or antibiotics; and absence of localized corpus atrophy, positivity for autoantibodies, or characteristic histologic findings suggestive of autoimmune gastritis. The risk of developing gastric cancer depends on the atrophic grade. The reported rate of developing gastric cancer is 0.31%-0.62% per year for successfully eradicated severely atrophic cases (pathophysiologically equal to unintentionally eradicated cases and unreported eradicated cases), and 0.53%-0.87% per year for spontaneously resolved cases due to severe atrophy. Therefore, for previous H. pylori infection-induced atrophic gastritis cases, we recommend endoscopic surveillance every 3 years for high-risk patients, including those with endoscopically severe atrophy or intestinal metaplasia. Because of the difficulty involved in the endoscopic diagnosis of gastric cancer in cases of previous infection, appropriate monitoring of the high-risk subgroup of this understudied population is especially important.

A long (7 cm) prophylactic pancreatic stent decreases incidence of post-endoscopic papillectomy pancreatitis: a retrospective study.

Background and study aims Endoscopic papillectomy (EP) is a minimally invasive treatment for ampullary neoplasms and is recognized as an alternative treatment to surgical resection; however, there are few reports on a suitable pancreatic stent (PS) after EP for preventing pancreatitis. The aim of this study was to evaluate the efficacy of a long PS after EP. Patients and methods In this retrospective single-center study, 39 patients with pathologically proven ampullary neoplasms who underwent EP between March 2012 and August 2018 were enrolled. The study participants were divided into two subgroups according to the PS length: those with a PS shorter than 5 cm (short PS group, n = 17) and those with a PS of 7 cm (long PS group, n = 22). The incidence of adverse events and risk factors for pancreatitis were evaluated. Results The diameter of all PSs was 5 Fr. Post-EP pancreatitis occurred in nine patients (23.1 %), with two cases of severe pancreatitis (5.1 %). Pancreatitis occurred more frequently in the short PS group (7/17, 41.2 %) than in the long PS group (2/22, 9.1 %) ( P  = 0.026). There were no significant differences between the two groups in terms of other adverse events. Univariate and multivariate analyses showed that a long PS was the only factor associated with a decreased incidence of post-EP pancreatitis ( P  = 0.042; odds ratio, 0.16; 95 % confidence interval, 0.027-0.94). Conclusion A long (7 cm) PS significantly decreased incidence of pancreatitis after EP. Prospective randomized studies with a larger number of patients and wider range of PS lengths are required.

Electric Endocut and Autocut Resection for Endoscopic Papillectomy: A Systematic Review.

Objective Risks of bleeding and pancreatitis after mucosal resection using the purecut/autocut and blendcut/endocut modes for endoscopic papillectomy have not been fully clarified. Thus, a systematic review on electrosurgical cutting modes for endoscopic papillectomy was conducted focusing on the types and incidence of adverse events. Methods We searched the PubMed and Cochrane library for cases of endoscopic papillectomy recorded as of April 2017. Studies reporting the methods of electrically excising a tumor in the duodenal papilla and the number of adverse events were extracted. Studies were collected and examined separately based on the electrosurgical cutting mode, and the incidence rate for each adverse event was summarized. Results A total of 159 relevant articles were found; among them, 20 studies were included and 139 excluded. Five studies analyzed endoscopic papillectomy with the purecut/autocut mode and 16 with the blendcut/endocut mode. Only one study investigated both modes (purecut and endocut). With the purecut/autocut mode, the incidence of bleeding was 2.8-50%, and that of pancreatitis was 0-50% (mean: 12.8%). With the blendcut/endocut mode, the incidence of bleeding was 0-42.3%, and that of pancreatitis was 0%-17.9% (mean: 9.5%). Conclusion Both methods had high adverse event rates for endoscopic papillectomy. Thus, a standard method of endoscopic papillectomy, including the electrosurgical cutting mode, needs to be established.

Novel mainstream capnometer system is safe and feasible even under CO2 insufflation during ERCP-related procedure: a pilot study.

BACKGROUND AND AIMS: There is a need to safely achieve conscious sedation during endoscopic retrograde cholangiopancreatography (ERCP). We evaluated the safety and feasibility of a mainstream capnometer system to monitor apnoea during ERCP under CO2 insufflation. METHODS: Non-intubated adult patients undergoing ERCP-related procedures with intravenous sedation were enrolled. End-tidal CO2 (EtCO2) was continuously monitored during the procedure under CO2 insufflation using a mainstream capnometer system, comprising a capnometer and a specially designed bite block for upper gastrointestinal endoscopy and ERCP. Oxygen saturation (SpO2) was also monitored continuously during the procedure. In this study, we evaluated the safety and feasibility of the capnometer system. RESULTS: Eleven patients were enrolled. Measurement of EtCO2 concentration was possible from the beginning to the end of the procedure in all 11 cases. There was no measurement failure, dislocation of the bite block, or adverse event related to the bite block. Apnoea linked to hypoxaemia occurred five times (mean duration, 174.4 s). CONCLUSION: This study confirmed that apnoea was detected earlier than when using a percutaneous oxygen monitor. Measurement of EtCO2 concentration using the newly developed mainstream capnometer system was feasible and safe even under CO2 insufflation.

Successful EUS-guided antegrade stenting for malignant severe biliary obstruction combined with a newly developed plastic stent.

Background and study aims We report the effectiveness of a newly developed plastic stent for preventing bile leakage after endoscopic ultrasonography (EUS)-guided antegrade stenting. This treatment was performed on a 59-year-old woman with malignant obstructive jaundice caused by peritoneal metastasis. First, we attempted transpapillary drainage using short-type single-balloon enteroscopy-assisted endoscopic retrograde cholangiopancreatography, but we could not achieve it. We then attempted EUS-guided antegrade stenting through the intrahepatic bile duct from the esophagojejunal anastomosis. We successfully inserted uncovered metallic stents for common bile duct and a newly plastic stent for hepaticojejunostomy from the antegrade approach. There were no adverse events after the treatment.

Intestinal barrier regulates immune responses in the liver via IL-10-producing macrophages.

The gut-liver axis is of clinical importance as a potential therapeutic target in a wide range of liver diseases; however, the mechanisms underlying interactions between microbial products and immune responses in the liver remain unknown. In this study, we demonstrated that IL-10-producing macrophages contribute to immune tolerance in the inflamed liver under intestinal barrier disruption in a murine tandem model of dextran sulfate sodium (DSS) colitis and concanavalin A (Con A) hepatitis. Intestinal barrier disruption protected mice from subsequent liver injury, and the severity of colitis directly affected susceptibility to such injury. The protective effect of DSS-Con A was canceled in gut-sterilized mice, suggesting that gut microbiota play a substantial role in this process. Altered gut microbiota and their metabolites, along with a disrupted intestinal barrier, directly gave rise to immunological permissiveness in the inflamed liver. We identified 1-methylnicotinamide (1-MNA) as a candidate metabolite capable of suppressing liver injury with the potential to induce IL-10-producing macrophages. Consistently, expression of nicotinamide N-methyltransferase, which converts nicotinamide to 1-MNA, was upregulated in the liver of DSS-Con A mice, and this effect was abrogated by gut sterilization. Collectively, our results provide a mechanistic insight into the regulation of immunological balance in the liver via the gut-liver axis.