Drug-induced mucosal alterations observed during esophagogastroduodenoscopy.

Several features of drug-induced mucosal alterations have been observed in the upper gastrointestinal tract, i.e., the esophagus, stomach, and duodenum. These include pill-induced esophagitis, desquamative esophagitis, worsening of gastroesophageal reflux, chemotherapy-induced esophagitis, proton pump inhibitor-induced gastric mucosal changes, medication-induced gastric erosions and ulcers, pseudomelanosis of the stomach, olmesartan-related gastric mucosal inflammation, lanthanum deposition in the stomach, zinc acetate hydrate tablet-induced gastric ulcer, immune-related adverse event gastritis, olmesartan-asso-ciated sprue-like enteropathy, pseudomelanosis of the duodenum, and lanthanum deposition in the duodenum. For endoscopists, acquiring accurate knowledge regarding these diverse drug-induced mucosal alterations is crucial not only for the correct diagnosis of these lesions but also for differential diag-nosis of other conditions. This minireview aims to provide essential information on drug-induced mucosal alterations observed on esophagogastroduodenoscopy, along with representative endoscopic images.

Endoscopic and Histological Gastritis in University Students with Helicobacter pylori Infection.

Objective Although the characteristics of Helicobacter pylori infection have been extensively reported, there is a lack of consensus regarding its characteristics in young adults. The present study examined the endoscopic and histological characteristics of young adults who underwent eradication therapy for H. pylori infection. Methods We examined the H. pylori infection status of first-year students at Okayama University School of Medicine and Dentistry between 2014 and 2020. A total of 152 (6.8%) students who were positive for H. pylori antibody or pepsinogen tests were enrolled in the study. Among them, 107 students underwent endoscopy, and their biopsy samples were investigated. Seventy-five students were diagnosed with H. pylori infections. Results Of 75 H. pylori-positive patients, 57 (76.0%) had endoscopic atrophic gastritis, and 42 (56.0%) had histological atrophy. A few patients had severe atrophic gastritis. All 65 patients who underwent an eradication assessment were successfully treated. After successful eradication, 26 patients underwent endoscopic follow-up. The mean follow-up period was 32.9 months. A histological evaluation revealed that gastric antrum atrophy had subsided in 11 of 14 patients, and atrophy in the lesser curvature of the gastric body had subsided in 7 of 8 patients. Conclusion More than half of young adults with H. pylori infection had atrophic gastritis. We found mild atrophy in young adults, which subsided shortly after eradication treatment. This study provides a foundation for future studies to evaluate the validity of eradication therapy in preventing gastric cancer in patients.

Clinical significance of gastrointestinal bleeding history in patients who undergo left atrial appendage closure.

Background and Aim: Anticoagulant users with nonvalvular atrial fibrillation (NVAF) sometimes suffer from gastrointestinal bleeding (GIB) and have difficulty continuing the medication. Left atrial appendage closure (LAAC) has been developed for such situations. We aimed to clarify the clinical significance of a history of GIB in comparison to other factors in patients who had undergone LAAC. Methods: From October 2019 to September 2023, patients with NVAF who underwent LAAC at our hospital were enrolled. We investigated the percentage of patients with a history of GIB who underwent LAAC and compared the incidence of post-LAAC bleeding in these patients compared to those with other factors. Results: A total of 45 patients were included. There were 19 patients (42%) with a history of GIB who underwent LAAC. In a Kaplan-Meier analysis, the cumulative incidence of bleeding complications after LAAC was significantly higher in patients with a history of GIB in comparison to patients with other factors. There were eight cases of post-LAAC bleeding in total, and seven cases had GIB. Conclusions: We need to recognize that GIB is a significant complication in patients who undergo LAAC. The management of GIB by gastroenterologists is essential to the success of LAAC.

Innovative submucosal injection solution for endoscopic resection with phosphorylated pullulan: a preclinical study.

BACKGROUND AND AIMS: A submucosal injection solution is used to assist in endoscopic surgery. The high viscosity of current solutions makes them difficult to inject. In the present study, we developed an extremely low-viscosity, easy-to-use submucosal injection solution using phosphorylated pullulan (PPL). METHODS: The PPL solutions were prepared at different concentrations, and their viscosities were measured. The mucosal elevation capacity was evaluated using excised porcine stomachs. Controls included 0.4% sodium hyaluronate (SH), 0.6% sodium alginate (SA), and saline. To evaluate the practicality, the catheter injectability of 0.7% PPL was measured, and EMR and endoscopic submucosal dissection (ESD) were performed using the stomach and colorectum of live pigs. As controls, 0.4% SH and saline were used. RESULTS: The PPL solutions were of extremely low viscosity compared to the solutions of 0.4% SH and 0.6% SA. Nevertheless, the mucosal elevation capacity of PPL solutions for up to 0.7% concentration was similar to that of 0.4% SH, and 0.7% PPL was less resistant to catheter infusion than 0.4% SH and 0.6% SA. In live pig experiments with endoscopic mucosal resection and ESD, snaring after submucosal injection of 0.7% PPL was easier than with 0.4% SH, ESD with 0.7% PPL produced less bubble formation than with 0.4% SH, and the procedure time tended to be shorter with 0.7% PPL than with 0.4% SH because of the shorter injection time. CONCLUSIONS: The PPL solution is an innovative and easy-to-use submucosal injection solution.

Nationwide multicenter study on adverse events associated with a patency capsule: Additional survey of appropriate use of patency capsule study.

BACKGROUND AND AIM: The PillCam patency capsule (PC) without a radio frequency identification tag was released to preclude retention of the small bowel capsule endoscope (CE) in Japan in 2012. We conducted a multicenter study to determine tag-less PC-related adverse events (AEs). METHODS: We first conducted a retrospective survey using a standardized data collection sheet for the clinical characteristics of PC-related AEs among 1096 patients collected in a prospective survey conducted between January 2013 and May 2014 (Cohort 1). Next, we retrospectively investigated additional AEs that occurred before and after Cohort 1 within the period June 2012 and December 2014 among 1482 patients (Cohort 2). RESULTS: Of the 2578 patients who underwent PC examinations from both cohorts, 74 AEs occurred among 61 patients (2.37%). The main AEs were residual parylene coating in 25 events (0.97%), PC-induced small bowel obstruction, suspicious of impaction, in 23 events (0.89%), and CE retention even after patency confirmation in 10 events (0.39%). Residual parylene coating was significantly associated with Crohn's disease (P < 0.01). Small bowel obstruction was significantly associated with physicians with less than 1 year of experience handling the PC and previous history of postprandial abdominal pain (P < 0.01 and P < 0.03, respectively). CE retention was ascribed to erroneous judgment of PC localization in all cases. CONCLUSIONS: This large-scale multicenter study provides evidence supporting the safety and efficiency of a PC to preclude CE retention. Accurate PC localization in patients without excretion and confirmation of previous history of postprandial abdominal pain before PC examinations is warranted (UMIN000010513).

Successful use of dupilumab for egg-induced eosinophilic gastroenteritis with duodenal ulcer: a pediatric case report and review of literature.

BACKGROUND: Non-esophageal eosinophilic gastrointestinal disorder (non-EoE-EGID) is a rare disease in which eosinophils infiltrate parts of the gastrointestinal tract other than the esophagus; however, the number of patients with non-EoE-EGID has been increasing in recent years. Owing to its chronic course with repeated relapses, it can lead to developmental delays due to malnutrition, especially in pediatric patients. No established treatment exists for non-EoE-EGID, necessitating long-term systemic corticosteroid administration. Although the efficacy of dupilumab, an anti-IL-4/13 receptor monoclonal antibody, for eosinophilic esophagitis, has been reported, only few reports have demonstrated its efficacy in non-EoE EGIDs. CASE PRESENTATION: A 13-year-old boy developed non-EoE-EGID with duodenal ulcers, with chicken eggs as the trigger. He was successfully treated with an egg-free diet, proton pump inhibitors, and leukotriene receptor antagonists. However, at age 15, he developed worsening upper abdominal pain and difficulty eating. Blood analysis revealed eosinophilia; elevated erythrocyte sedimentation rate; and elevated levels of C-reactive protein, total immunoglobulin E, and thymic and activation-regulated chemokines. Upper gastrointestinal endoscopy revealed a duodenal ulcer with marked mucosal eosinophilic infiltration. Gastrointestinal symptoms persisted even after starting systemic steroids, making it difficult to reduce the steroid dose. Subcutaneous injection of dupilumab was initiated because of comorbid atopic dermatitis exacerbation. After 3 months, the gastrointestinal symptoms disappeared, and after 5 months, the duodenal ulcer disappeared and the eosinophil count decreased in the mucosa. Six months later, systemic steroids were discontinued, and the duodenal ulcer remained recurrence-free. The egg challenge test result was negative; therefore, the egg-free diet was discontinued. Blood eosinophil count and serum IL-5, IL-13, and eotaxin-3 levels decreased after dupilumab treatment. The serum levels of IL-5 and eotaxin-3 remained within normal ranges, although the blood eosinophil counts increased again after discontinuation of oral prednisolone. CONCLUSIONS: Suppression of IL-4R/IL-13R-mediated signaling by dupilumab may improve abdominal symptoms and endoscopic and histologic findings in patients with non-EoE-EGID, leading to the discontinuation of systemic steroid administration and tolerance of causative foods.

Optimal Bowel Preparation Method to Visualize the Distal Ileum via Small Bowel Capsule Endoscopy.

Small bowel capsule endoscopy (SBCE) is a convenient and minimally invasive method widely used to evaluate the small intestine. However, especially in the distal ileum, visualization of the intestinal mucosa is frequently hampered by the remaining intestinal contents, making it difficult to detect critical lesions. Although several studies have reported on the efficacy of bowel preparation before SBCE, no standardized protocol has been established. Herein, we determined the optimal preparation method for better visualization of the distal ileum using SBCE. We retrospectively analyzed 259 consecutive patients who had undergone SBCE between July 2009 and December 2019, divided into three groups: Group A (no preparation except overnight fasting), Group B (ingestion of 1-2 L polyethylene glycol 4 h before colonoscopy after overnight fasting and performing SBCE immediately after colonoscopy), and Group C (ingestion of 0.9 L magnesium citrate [MC] before SBCE after overnight fasting). The visibility of the intestinal mucosa in the first 10 min and at the last 10 min during the period of observation of the distal ileum was examined using a scoring system and compared. The visibility of the images captured by SBCE was assessed based on the scoring of the degree of bile/chyme staining, residual fluid and debris, brightness, bubble reduction, and visualized mucosa. The status of intestinal collapse was also assessed. In the first 10 min of observation of the distal ileum, no significant differences were detected among the groups. In the last 10 min, significantly better images were acquired in Group C in terms of bile/chyme staining, brightness, bubble reduction, and visualized mucosa. Bowel preparation using a low-dose MC solution 2 h before SBCE provided significantly higher-quality images of the distal ileum. Further optimization, such as the timing of initiating the preparation, is necessary to determine the optimal regimen for bowel preparation prior to SBCE.

Idiopathic Gastric Antral Ulcers.

A Japanese woman presented with gastric antral ulcers accompanied by erosion and edema, demonstrating a chronic pattern of improvement and recurrence for more than six years. The patient had no relevant treatment history, and Helicobacter pylori infection was ruled out. Other potential etiologies contributing to gastric ulcers were eliminated on the basis of endoscopic biopsy and blood laboratory findings. Consequently, the patient was diagnosed with idiopathic gastric antral ulcer. This disease is often overlooked, and the chronological endoscopic images provided in this report can be used as a reference.

Endoscopic features of gastric neuroendocrine carcinoma.

BACKGROUND AND AIM: The endoscopic features of gastric neuroendocrine carcinoma (G-NEC) have not been clarified; therefore, they were investigated in relation to clinicopathological findings. METHODS: Consecutive patients with G-NECs who had undergone endoscopic or surgical resection at our institution between January 2005 and March 2022 were included in this retrospective study. The endoscopic and clinicopathological findings of the lesions were analyzed to provide information of diagnostic value. In addition, cases of gastric neuroendocrine tumor (G-NET) and common-type gastric adenocarcinoma treated in the same study period were identified to compare the endoscopic findings between each G-NEC versus G-NET, and G-NEC versus common-type gastric adenocarcinoma. Patients with common-type gastric adenocarcinoma were matched for age, sex, tumor size, and depth of tumor invasion in 1:3 ratio. RESULTS: Among 15 patients with 15 G-NECs, submucosal tumor-like marginal elevation (87%), adherent white coat (67%), and ulceration with a distinct border (60%) were characteristic endoscopic findings in white-light images. Magnifying narrow-band imaging endoscopy revealed an absent microsurface (MS) pattern plus disrupted irregular microvessel (MV) in five (71%) of seven cases with evaluable MS and MV patterns. The area with an absent MS pattern plus disrupted irregular MV corresponded to the histological finding of NEC component in all five cases. These endoscopic features were all significantly more frequent in G-NECs than G-NETs (n = 22) or common-type gastric adenocarcinomas (n = 45). CONCLUSIONS: These endoscopic features should be taken into consideration to increase the index of suspicion and to improve the accuracy of target biopsies for G-NEC.

Review of oral and pharyngolaryngeal benign lesions detected during esophagogastroduodenoscopy.

Recent advancements in endoscopy equipment have facilitated endoscopists' detection of neoplasms in the oral cavity and pharyngolaryngeal regions. In particular, image-enhanced endoscopy using narrow band imaging or blue laser imaging play an integral role in the endoscopic diagnosis of oral and pharyngolaryngeal cancers. Despite these advancements, limited studies have focused on benign lesions that can be observed during esophagogastroduodenoscopy in the oral and pharyngolaryngeal regions. Therefore, this mini-review aimed to provide essential information on such benign lesions, along with representative endoscopic images of dental caries, cleft palate, palatal torus, bifid uvula, compression by cervical osteophytes, tonsil hyperplasia, black hairy tongue, oral candidiasis, oral and pharyngolaryngeal ulcers, pharyngeal melanosis, oral tattoos associated with dental alloys, retention cysts, papilloma, radiation-induced changes, skin flaps, vocal cord paresis, and vocal fold leukoplakia. Whilst it is imperative to seek consultation from otolaryngologists or dentists in instances where the diagnosis cannot be definitively ascertained by endoscopists, the merits of attaining foundational expertise pertaining to oral and pharyngolaryngeal lesions are unequivocal. This article will be a valuable resource for endoscopists seeking to enhance their understanding of oral and pharyngolaryngeal lesions.

Exosomes derived from synovial fibroblasts from patients with rheumatoid arthritis promote macrophage migration that can be suppressed by miR-124-3p.

Objectives: Exosomes are potent vehicles for intercellular communication. Rheumatoid arthritis (RA) is a chronic systemic disease of unknown etiology. Local administration of miR-124 precursor to rats with adjuvant-induced arthritis suppresses systemic arthritis and bone destruction. Thus, exosomes may be involved in this disease. We aimed to determine the role of exosomes in the pathology of RA. Methods: Fibroblast-like synoviocytes (FLS) were collected from patients with RA and osteoarthritis (OA). miR-124-3p mimic was transfected into the RA FLS (RA miR-124 FLS). Exosomes were collected from the culture medium by ultracentrifugation. Macrophages were produced from THP-1 cells. MicroRNAs in the exosomes were analyzed using real-time PCR. Proteomics analysis was performed using nanoscale liquid chromatography-tandem mass spectrometry. Macrophage migration was evaluated using a Transwell migration assay. SiRNA was used to knockdown proteins of interest. Results: MicroRNAs in the RA FLS, RA miR-124 FLS, and OA FLS exosomes were similar. Proteomics analysis revealed that pentraxin 3 (PTX3) levels were higher in RA FLS exosomes than in RA miR-124 FLS and OA FLS exosomes, and proteasome 20S subunit beta 5 (PSMB5) levels were lower in RA FLS exosomes than in RA miR-124 FLS and OA FLS exosomes. The RA FLS exosomes promoted and the RA miR-124 FLS exosomes suppressed macrophage migration. PTX3-silenced RA FLS exosomes suppressed and PSMB5-silenced OA FLS exosomes promoted macrophage migration. Conclusions: RA FLS exosomes promote macrophage migration via PTX3 and PSMB5, and miR-124-3p suppresses this migration.

Degree of pharyngeal deformation caused by pharyngeal endoscopic submucosal dissection is associated with the incidence of aspiration pneumonia.

Background and study aims Endoscopic submucosal dissection (ESD) is one of the most minimally invasive treatments for superficial squamous cell cancer of the pharynx. However, aspiration pneumonia (AsP) associated with postoperative deformity of the pharynx may occur. The purpose of this study was to investigate the frequency of AsP and the degree of pharyngeal deformity after pharyngeal ESD. Patients and methods This was a retrospective observational study of patients who underwent pharyngeal ESD at Okayama University Hospital between 2006 and 2017. The degree of pharyngeal deformation was assessed using the pharyngeal deformation grade (PDG). The primary endpoint was the frequency of AsP as a long-term adverse event. Results Among the 52 patients enrolled, nine developed aspiration pneumonia, with a 3-year cumulative incidence of 9.0 % (95 % confidence interval [CI], 3.3 %-22.0 %). There were 16, 18, 16, and two patients that had PDG 0, 1, 2, and 3, respectively. Patients with a history of radiotherapy, as a treatment of head and neck cancer (44.4 % vs. 11.6 %; P  = 0.02) and the high PDG group (PDG 2 and 3) (77.8 % vs. 25.6 %; P  = 0.005) had a significantly higher incidence of AsP. The 3-year cumulative incidence rate of AsP after ESD in the high PDG group was significantly higher than that in the low PDG group (PDG 0 and 1) (23.9 % [95 %CI, 9.2.-49.5%] vs. 0 %; P  = 0.03). Conclusions The incidence of aspiration pneumonia in the long-term course after pharyngeal ESD was revealed. The incidence of aspiration pneumonia may be associated with pharyngeal deformity, but further studies are needed.

Improved Object Detection Artificial Intelligence Using the Revised RetinaNet Model for the Automatic Detection of Ulcerations, Vascular Lesions, and Tumors in Wireless Capsule Endoscopy.

The use of computer-aided detection models to diagnose lesions in images from wireless capsule endoscopy (WCE) is a topical endoscopic diagnostic solution. We revised our artificial intelligence (AI) model, RetinaNet, to better diagnose multiple types of lesions, including erosions and ulcers, vascular lesions, and tumors. RetinaNet was trained using the data of 1234 patients, consisting of images of 6476 erosions and ulcers, 1916 vascular lesions, 7127 tumors, and 14,014,149 normal tissues. The mean area under the receiver operating characteristic curve (AUC), sensitivity, and specificity for each lesion were evaluated using five-fold stratified cross-validation. Each cross-validation set consisted of between 6,647,148 and 7,267,813 images from 217 patients. The mean AUC values were 0.997 for erosions and ulcers, 0.998 for vascular lesions, and 0.998 for tumors. The mean sensitivities were 0.919, 0.878, and 0.876, respectively. The mean specificities were 0.936, 0.969, and 0.937, and the mean accuracies were 0.930, 0.962, and 0.924, respectively. We developed a new version of an AI-based diagnostic model for the multiclass identification of small bowel lesions in WCE images to help endoscopists appropriately diagnose small intestine diseases in daily clinical practice.

Erratum: Differences in color between early gastric cancer and cancer-suspected non-cancerous mucosa on linked color imaging.

[This corrects the article DOI: 10.1055/a-1989-6643.].

Scattered Tiny Whitish Protrusions in the Stomach Are a Clue to the Diagnosis of Autoimmune Gastritis.

Herein, we report two patients with autoimmune gastritis who had undergone multiple esophagogastroduodenoscopy procedures for 17 and 9 years, respectively, before their diagnosis. Instead, they had been diagnosed with and treated for Helicobacter pylori-associated gastritis. The correct diagnosis was made when scatterings of tiny whitish protrusions in the gastric mucosa were detected on esophagogastroduodenoscopy. Our findings suggest that scattered tiny whitish bumps may be a clue to the diagnosis of autoimmune gastritis.

Differences in color between early gastric cancer and cancer-suspected non-cancerous mucosa on linked color imaging.

Background and study aims Linked color imaging (LCI) can enhance the original color of each area and may useful to detect tumorous lesions during esophagogastroduodenoscopy. However, LCI may also enhance cancer-suspected non-cancerous regional color change. We conducted a retrospective image analysis to investigate the color characteristics of early gastric cancer (EGC) and cancer-suspected non-cancerous mucosa (CSM) in LCI. Methods LCI images of both EGC and CSM were retrospectively collected from the database of the institution. Fifteen endoscopists individually judged each image as EGC or CSM. The color difference between the inside and outside of the lesions was measured by CIE-Lab analysis in both groups and compared. Results A total of 245 LCI images of EGC (169) and CSM (76) were extracted and randomly lined for image collection. The test by the endoscopists showed accuracy, sensitivity, and specificity of 64.0 %, 63.7 %, and 64.0 %, respectively. Although the color difference between EGC and CSM was almost the same (12.5 vs. 12.9, not significant), each parameter of ΔL (bright: -0.3 vs. -2.7, P  < 0.001), Δa (Reddish: 7.2 vs. 9.6, P  = 0.004), and Δb (Yellowish: 6.4 vs. 3.8, P  < 0.001) was significantly different in the groups. The color feature of both positive ΔL and Δb to EGC showed accuracy, sensitivity, and specificity of 54.7 %, 39.6 %, 88.2%, respectively. Conclusions The total color difference was almost the same between EGC and CSM; however, their color tones were different on linked color imaging. Although the color characteristics of EGC had high specificity, they also had low sensitivity.

Usefulness of Intestinal Ultrasound to Detect Small Intestinal Stenosis in Patients With Crohn's Disease.

OBJECTIVES: Double balloon enteroscopy (DBE) with retrograde contrast is useful as a monitoring tool for small intestinal lesions in Crohn's disease (CD), but these are burdensome for patients. Intestinal ultrasound (IUS) can be used with ease in daily clinical practice, but there is less evidence regarding the accuracy of detection of small intestinal stenosis in CD. This study aimed to examine the diagnostic power of IUS for small intestinal stenosis in patients with CD. METHODS: The findings of DBE and IUS in 86 patients with CD with small intestinal lesions were evaluated. Using DBE as the reference standard, we examined the detection rate of IUS for small intestinal stenosis. We evaluated three parameters: luminal narrowing, prestenotic dilation, and to-and-fro movement for determining stenosis using IUS. In addition, we compared the characteristics between the stenosis-detectable and stenosis-undetectable groups by IUS. RESULTS: Of the 86 patients, 30 had small intestinal stenosis. In IUS findings, when lesions that met two or more of the three parameters were judged as stenosis, the detection rate was 70.0% for sensitivity, 98.2% for specificity, and 88.4% for accuracy. Moreover, there were patients with a younger age at diagnosis (P < 0.05) and more ileocolonic disease location (P < 0.05) in the stenosis-detectable group by IUS. The stenoses detected by IUS were significantly longer than those undetected by IUS (14.1 mm versus 5.2 mm, P < 0.05). CONCLUSIONS: IUS delivered reliable results for clinically important small intestinal stenosis of CD with high diagnostic accuracy.