Phase concept: Novel dynamic endoscopic assessment of intramural antireflux mechanisms (with video).

OBJECTIVES: The gastroesophageal junction (GEJ) consists of various anatomical components that together form a barrier to prevent reflux of gastric content. This study introduces a novel phase concept to dynamically evaluate the antireflux barrier (ARB) during endoscopy and analyzes its functionality. METHODS: We reviewed previously the recorded endoscopic videos of subjects who underwent the endoscopic pressure study integrated system (EPSIS) from February to April 2024 for indications other than gastroesophageal reflux disease symptoms. This device was used as an auxiliary tool to measure intragastric pressure (IGP) during endoscopy with a retroflex view. The ARB dynamic was divided into three phases: Phase I (gastric phase), Phase II (lower esophageal sphincter phase), and Phase III (esophageal clearance phase). We evaluated the morphological changes in the ARB during insufflation using EPSIS. RESULTS: The median age of the 30 subjects was 58 years (interquartile range [IQR] 46.5-68.8), including 20 men and 10 women. Endoscopic findings and IGPs were recorded during the three phases. In Phase I, at low IGP (median 6.75 mmHg), the gastroesophageal flap valve and longitudinal folds were observed in 80% of cases. In Phase II, at moderate IGP (median 11.8 mmHg), the scope holding sign was observed in 86.7%. In Phase III, at high IGP (median 19 mmHg) inducing belching, peristalsis was observed in 80% of cases with median recovery time of 5 s. CONCLUSION: The phase concept provides a valuable framework for understanding the antireflux mechanism. Further research is needed to validate these findings in GEJ disorders and explore correlations with other modalities.

Very urgent endoscopic retrograde cholangiopancreatography is associated with early discharge in patients with non-severe acute cholangitis.

BACKGROUND: endoscopic retrograde cholangiopancreatography (ERCP) is a first-line procedure for biliary drainage in patients with acute cholangitis, and there are no studies focused on very urgent ERCP within several hours of hospital arrival. This study aimed to elucidate the use of very urgent ERCP for non-severe acute cholangitis. METHODS: this retrospective observational study included patients with non-severe acute cholangitis who underwent ERCP between April 2011 and June 2020 in our institution. Patients were stratified into three groups based on time to ERCP after hospital arrival: very urgent (≤ 3 hours), urgent (3-24 hours) and elective (> 24 hours). The primary outcome was length of hospital stay (LOS). RESULTS: the study cohort included 291 patients, 168 males (57.7 %), with a median age of 76 (interquartile range, 70-83) years. In all, 47, 196 and 48 patients underwent very urgent, urgent and elective ERCP, respectively. Median LOS in the very urgent, urgent, and elective groups was 12, 14, and 15 days, respectively (Kaplan-Meier method). A shorter LOS was associated with earlier ERCP (log-rank trend test, p = 0.04). The rates of readmission within 30 days of discharge and of adverse events were not significantly different among the three groups. By multivariate analysis, very urgent ERCP was associated with a significantly earlier discharge than urgent and elective ERCP (HR, 0.71, p = 0.04 and HR, 0.47, p < 0.01, respectively). In addition, age ≥ 75 years, pancreatitis, albumin ≤ 2.8 g/dL and two or more ERCP procedures were associated with a significantly longer LOS (HRs < 1, p < 0.05). CONCLUSIONS: very urgent ERCP for non-severe acute cholangitis was associated with early discharge.

Feasibility of a modified search, coagulation, and clipping method with and without the use of polyglycolic acid sheets and fibrin glue for preventing delayed bleeding after gastric endoscopic submucosal dissection.

BACKGROUND: Methods have been developed for preventing delayed bleeding (DB) after gastric endoscopic submucosal dissection (GESD). However, none of the methods can completely prevent DB. We hypothesized that DB could be prevented by a modified search, coagulation, and clipping (MSCC) method for patients at low risk for DB and by combining the use of polyglycolic acid sheets and fibrin glue with the MSCC method (PMSCC method) for patients at high risk for DB (antibleeding [ABI] strategy). This study assessed the technical feasibility of this novel strategy. METHOD: We investigated 123 lesions in 121 consecutive patients who underwent GESD in Kushiro Rosai Hospital between April 2018 and January 2020. The decision for continuation or cessation of antithrombotic agents was based on the Guidelines for Gastroenterological Endoscopy in Patients Undergoing Antithrombotic Treatment. RESULTS: Oral antithrombotic agents were administered to 28 patients (22.8%). The en bloc R0 resection rate was 98.4%. The MSCC method and the PMSCC method for preventing DB were performed in 114 and 9 lesions, respectively. The median time of the MSCC method was 16 min, and the median speed (the resection area divided by the time of method used) was 3.6 cm2/10 min. The median time of the PMSCC method was 59 min, and the median speed was 1.3 cm2/10 min. The only delayed procedural adverse event was DB in 1 (0.8%) of the 123 lesions. CONCLUSIONS: The ABI strategy is feasible for preventing DB both in patients at low risk and in those at high risk for DB after GESD, whereas the PMSCC method may be necessary for reduction of time.

A case of Epstein-Barr virus-associated lymphoepithelioma-like carcinoma of the colon.

Lymphoepithelioma-like carcinoma is a poorly differentiated carcinoma with prominent lymphoid infiltration occurring in various organs but is exceedingly rare in the colorectal region. This malignancy is frequently associated with Epstein-Barr virus (EBV). Here we report a case of EBV-associated lymphoepithelioma-like carcinoma of the cecum in an 84-year-old male who presented with occult blood. In situ hybridization for EBV-encoded small RNAs (EBER) in an endoscopic submucosal dissection specimen showed that the tumor consisted of EBER-negative well-differentiated tubular adenocarcinoma and EBER-positive lymphoepithelioma-like carcinoma. Real-time PCR detected 7.16 copies of the EBV genome per cell in a sample microdissected from the latter component. Genotyping analysis demonstrated EBV genotype 1, and viral protein/transcript expression in the tumor showed EBV latency I. Expression of Ephrin receptor A2, a recently reported receptor for EBV, was demonstrated in the tumor cells by immunohistochemistry. To our knowledge, this is the first report of lymphoepithelioma-like carcinoma in the colorectal region showing a definite association with EBV infection.

Feasibility of a new ligation using the double-loop clips technique without an adhesive agent for ulceration after endoscopic submucosal dissection of the colon (with video).

BACKGROUND AND AIMS: Several ligation techniques for ulceration after endoscopic submucosal dissection (ESD) have been reported, but none have been established for clinical use because of technical complexity and the need for expensive equipment. Therefore, the technical feasibility of a new ligation method using the double-loop clips (D-L clips) technique without an adhesive agent for ulceration after ESD of the colon was assessed. METHODS: Among 35 patients who underwent ESD of the colon in Kushiro Rosai Hospital between April 2019 and September 2019, 26 patients who underwent ligation using the D-L clips technique for the post-ESD ulcer bed were included in this retrospective study. Continuation or cessation of antithrombotic agents was based on the Guidelines for Gastroenterological Endoscopy in Patients Undergoing Antithrombotic Treatment. RESULTS: The rate of en bloc R0 resection was 97.1%, the median length of the resected specimen was 3.2 cm (interquartile range [IQR], 2.8-3.8 cm), and the complete ligation rate was 88.5% (23 of 26). Excluding patients with lesion sites in the rectum below the peritoneal reflection, the complete ligation rate was 95.5% (21 of 22). The median duration of the ligation procedure was 20 minutes (IQR, 16-24 minutes). The only delayed procedural adverse event was post-ESD coagulation syndrome in 1 patient. Incomplete ligation was significantly more frequent in patients with lesion sites in the inferior rectal valve/anal verge area (P = .0269). CONCLUSIONS: Ligation using the D-L clips technique without an adhesive agent is feasible for closing ulceration after ESD of the colon, whereas other techniques may be necessary for lesions in the rectum below the peritoneal reflection.

Long-term outcome of endoscopic resection for intramucosal esophageal squamous cell cancer: a secondary analysis of the Japan Esophageal Cohort study.

BACKGROUND: Prospectively collected long-term data of patients undergoing endoscopic resection for superficial esophageal squamous cell carcinoma (ESCC) are limited. The aim of this study was to determine the prospectively collected long-term outcomes of endoscopic resection for ESCC as a secondary analysis of the Japan Esophageal Cohort (JEC) study. METHODS: Patients who underwent endoscopic resection of intramucosal ESCC at 16 institutions between September 2005 and May 2010 were enrolled in the JEC study. All patients underwent endoscopic examination with iodine staining at 3 and 6 months after resection, and every 6 months thereafter. We investigated clinical courses after endoscopic resection, survival rates, and cumulative incidence of metachronous ESCC. RESULTS: 330 patients (mean age 67.0 years) with 396 lesions (mean size 20.4 mm) were included in the analysis. Lesions were diagnosed as high-grade intraepithelial neoplasia in 17.4 % and as squamous cell carcinoma in 82.6 % (limited to epithelium in 28.4 %, to lamina propria in 55.4 %, and to muscularis mucosa in 16.2 %). En bloc resection was achieved in 291 (73.5 %). The median follow-up period was 49.4 months. Local recurrences occurred in 13 patients (3.9 %) and were treated by endoscopic procedures. Lymph node metastasis occurred in two patients (0.6 %) after endoscopic resection. The 5-year overall, disease-specific, and metastasis-free survival rates were 95.1 %, 99.1 %, and 94.6 %, respectively. The 5-year cumulative incidence rate of metachronous ESCC was 25.7 %. CONCLUSIONS: Our study demonstrated that endoscopic resection is an effective treatment for intramucosal ESCC, with favorable long-term outcomes.

Changes of Dyspeptic Symptom after Successful Eradication in Helicobacter pylori-Associated Dyspepsia.

BACKGROUND: Helicobacter pylori (H. pylori) gastritis could cause dyspepsia, and eradication is recommended as the first-line treatment. Patients who continuously have their symptoms under control > 6 months after eradication are defined as having H. pylori-associated dyspepsia (HPD), whereas patients who do not benefit from successful eradication are defined as having functional dyspepsia. OBJECTIVES: We assessed changes in dyspeptic symptoms after successful eradication of H. pylori by using a questionnaire. METHODS: We studied H. pylori-infected dyspeptic participants with abdominal symptom scores > 4 points on the Global Overall Symptom (GOS) scoring items and received eradication therapy. We evaluated their symptoms using the GOS questionnaire before their eradications, at 1-month and at 1-year check-ups after eradication therapy. RESULTS: Thirty dyspeptic participants (mean age 59.6 ± 15.3 years) answered every questionnaire. Fourteen participants (46.7%) had HPD, whereas 16 participants (53.3%) were non-HPD patients. The questionnaire at 1 month showed sensitivity of 64.3% (9/14) and specificity of 56.3% (9/16) for HPD. Approximately 60% of H. pylori-infected dyspepsia participants were identified as having HPD or non-HPD within 1 month after their eradications. CONCLUSIONS: Approximately 60% of HPD participants improved at 1 month after eradication. The questionnaire at 1 month helped diagnose HPD in advance and guided next treatment choice.

Cecum ulcer is a reliable endoscopic finding in cytomegalovirus colitis concomitant with graft-versus-host disease after allogeneic hematopoietic stem cell transplantation.

Although graft-versus-host disease (GVHD) is the major complication of allogeneic hematopoietic stem cell transplantation (allo-HSCT), cytomegalovirus (CMV) reactivation also occurs in patients after allo-HSCT and these conditions often clinically overlap. The aim of this study was to determine reliable endoscopic findings of CMV colitis in patients with gastrointestinal graft-versus-host-disease (GI-GVHD). Patients after allo-HSCT who were histologically confirmed to have GI-GVHD with or without CMV colitis and patients with an immunosuppressive condition were retrospectively analyzed. We divided the patients into three groups: GI-GVHD with CMV colitis (group A), GI-GVHD without CMV colitis (group B), and CMV colitis without undergoing allo-HSCT (group C). From medical records, the involved colorectal areas and endoscopic findings according to the groups were compared. A total of 70 patients were divided into three groups (group A: n = 19, group B: n = 28, group C: n = 23). Mucosal injuries in groups A and C frequently occurred in the cecum including ileocecal valves. On the other hand, there were no abnormal lesions on ileocecal valves in group B. Furthermore, ulcer lesions were more frequently observed in groups A and C than in group B (p < 0.001). The sensitivity and specificity of mucosal injuries in the cecum for prediction of CMV colitis were 89.5 and 76.5%, respectively, and mucosal injuries in the cecum were more reliable findings than CMV antigenemia. Ulcer lesions in the cecum are reliable endoscopic findings for CMV colitis in patients with GI-GVHD after allo-HSCT.

Preventive effect of mesenchymal stem cell culture supernatant on luminal stricture after endoscopic submucosal dissection in the rectum of pigs.

BACKGROUND: Mesenchymal stem cells (MSCs) are valuable in regenerative medicine, and MSC culture supernatant (MSC-CS) reportedly inhibits inflammation and fibrosis. We investigated whether colorectal luminal stricture develops after circumferential endoscopic submucosal dissection (ESD) in the colorectum, and whether the development of luminal stricture could be prevented by using MSC-CS enema. METHODS: In the first experiment, we performed circumferential ESD in the rectums or distal colons of pigs (n = 4 in each group). We sacrificed the pigs on Day 22 and measured the degree of luminal stricture. In the second experiment, we performed circumferential ESD in the rectums of pigs and administered an MSC-CS gel or a control gel enema after ESD for 4 days. We sacrificed the pigs on Day 8 (n = 3 in each group) or 22 (n = 3 in each group) to measure the degree of luminal stricture, and performed histological analysis. RESULTS: Severe luminal stricture was observed in the rectum but not in the distal colon. Moreover, fiber accumulation in the submucosa and hypertrophy of the muscularis propria were observed in the rectum but not in the distal colon. The degree of luminal stricture in the rectum was significantly lower in the MSC-CS group than in the control group. Furthermore, MSC-CS attenuated myofibroblast activation and hypertrophy of the muscularis propria on Day 22, and reduced inflammatory cell infiltration on Day 8. CONCLUSIONS: Luminal stricture after ESD developed only in the rectum because of the difference in myofibroblast activation and fiber accumulation. In addition, MSC-CS enema prevented luminal stricture after ESD, possibly by inhibiting the inflammatory reaction and fibrosis.

Lavender Color in Linked Color Imaging Enables Noninvasive Detection of Gastric Intestinal Metaplasia.

BACKGROUND AND AIMS: Recently, there have been some reports that image-enhanced endoscopy may improve detection of gastric intestinal metaplasia (GIM). Our aim was to determine the usefulness of linked color imaging (LCI) for detection of GIM. METHODS: In prospectively recruited patients, the whole antrum was observed by white light imaging (WLI) followed by LCI. When a whitish flat elevation (WFE) in WLI and a lavender color sign (LCS) in LCI were detected, target biopsies were performed after LCI. Random biopsies were performed in patients who had neither WFE nor LCS. The primary endpoint was the diagnostic accuracy of GIM per patient in WLI and LCI and the secondary endpoints were that of GIM per biopsy and interobserver agreement. RESULTS: Data from 128 patients were analyzed and 58 patients (45.3%) had histological GIM in the antrum. The per-patient yields of WLI and LCI to detect GIM were 19.0% (11/58) and 91.4% (53/58) respectively. Diagnostic accuracies of target biopsies for GIM were 23.7% in WLI and 84.2% in LCI. Kappa values among 3 doctors were 0.60 for WFE and 0.78 for LCS respectively. CONCLUSION: LCI could be a new diagnostic tool for detecting GIM during routine endoscopy.

Gastric mucosal cracked and cobblestone-like changes resulting from proton pump inhibitor use.

BACKGROUND AND AIM: Use of proton pump inhibitors (PPI) is histologically associated with oxyntic gland dilatations. Two interesting mucosal changes are often detected endoscopically in patients who use PPI: gastric cracked mucosa (GCM) and gastric cobblestone-like mucosa (GCSM). The aim of the present study was to clarify the relationship between PPI use and these mucosal changes. METHODS: This was a single-center observational study. All successive subjects who underwent a routine esophagogastroduodenoscopy (EGD) between August and November 2014 in Hokkaido University Hospital were enrolled. Endoscopists carried out the assessment blinded to the use of PPI and checked for GCSM and GCM using original diagnostic criteria for GCM and GCSM. Subjects were divided into two groups: those who used PPI (PPI group) and those who did not (control group). Endoscopic findings and backgrounds were compared between the two groups. RESULTS: A total of 538 patients were analyzed (control group: 374 patients, men/women: 204/170, median age: 65.2 years; PPI group: 164 patients, men/women: 89/75, median age: 67.1 years). GCM was detected in 54 (10.0%) subjects, and GCSM was detected in 18 (3.3%) subjects. There was a significant difference in the prevalence rate of GCM between the control group (14/374, 3.7%) and the PPI group (40/164, 24.4%) (P < 0.01). GCSM was significantly more prevalent in the PPI group (15/164, 9.1%) than in the control group (3/374, 0.8%) (P < 0.01). CONCLUSION: Novel GCM and GCSM endoscopic findings in the corpus area seem to be strongly associated with PPI use.