Updates to the modern diagnosis of GERD: Lyon consensus 2.0.

The Lyon Consensus provides conclusive criteria for and against the diagnosis of gastro-oesophageal reflux disease (GERD), and adjunctive metrics that consolidate or refute GERD diagnosis when primary criteria are borderline or inconclusive. An international core and working group was assembled to evaluate research since publication of the original Lyon Consensus, and to vote on statements collaboratively developed to update criteria. The Lyon Consensus 2.0 provides a modern definition of actionable GERD, where evidence from oesophageal testing supports revising, escalating or personalising GERD management for the symptomatic patient. Symptoms that have a high versus low likelihood of relationship to reflux episodes are described. Unproven versus proven GERD define diagnostic strategies and testing options. Patients with no prior GERD evidence (unproven GERD) are studied using prolonged wireless pH monitoring or catheter-based pH or pH-monitoring off antisecretory medication, while patients with conclusive GERD evidence (proven GERD) and persisting symptoms are evaluated using pH-impedance monitoring while on optimised antisecretory therapy. The major changes from the original Lyon Consensus criteria include establishment of Los Angeles grade B oesophagitis as conclusive GERD evidence, description of metrics and thresholds to be used with prolonged wireless pH monitoring, and inclusion of parameters useful in diagnosis of refractory GERD when testing is performed on antisecretory therapy in proven GERD. Criteria that have not performed well in the diagnosis of actionable GERD have been retired. Personalisation of investigation and management to each patient's unique presentation will optimise GERD diagnosis and management.

Mortality Risk Scoring System in Patients after Bleeding from Cancers in the Upper Gastrointestinal Tract.

Background/Aims: : Risk scoring systems for upper gastrointestinal (UGI) bleeding have not been well validated for tumor bleeding. This study aimed to identify risk factors for mortality in patients with UGI cancer bleeding and to develop a predictive model. Methods: : Consecutive patients with UGI cancers who underwent esophagogastroduodenoscopy for suspected bleeding were retrospectively included. Patient characteristics, endoscopic findings and 30-day mortality were assessed. A predictive model was made based on risk factors for mortality using logistic regression, and the area under the curve (AUC) of this model was calculated. It was then compared with other risk scoring systems. Results: : In a total of 264 patients, 193 had tumor bleeding. Among them, 108 (56.0%), 76 (39.4%), and nine (4.7%) patients received conservative treatment, endoscopic therapy, and non-endoscopic hemostasis, respectively. Rebleeding occurred in 23 (21.3%), 26 (34.2%), and one (11.1%) patient(s), respectively. Our new model is composed of altered mental status, renal failure, rebleeding, age older than 65 years, and low serum albumin (all p<0.05). This model predicted 30-day mortality with an AUC of 0.79 (95% confidence interval, 0.72 to 0.86), which was significantly higher than AUCs of the Glasgow-Blatchford score, Rockall, and AIMS65 score (AUC=0.61, 0.64, and 0.69, respectively, all p<0.05). Conclusions: : Our new scoring system provides a better prediction of 30-day mortality than existing scoring systems in patients with UGI cancer bleeding. This new scoring system can be used to predict and prepare these patients who are known to have high mortality.

Factors influencing occurrence of metachronous gastric cancer after endoscopic resection: a systematic review and meta-analysis.

BACKGROUND/AIMS: Metachronous gastric cancer (MGC) can occur after endoscopic resection for gastric cancer. Further studies on factors other than Helicobacter pylori infection are needed. This systematic review and meta-analysis aimed to evaluate risk factors for metachronous recurrence of endoscopically resected gastric cancer. METHODS: We searched medical literature published by February 2023 and identified patients with MGC after endoscopic resection for gastric cancer. The occurrence of MGC and the presence of intestinal metaplasia (IM), severe atrophic gastritis (AG), and H. pylori infection were quantitatively analyzed. RESULTS: We identified 2,755 patients from nine cohort studies who underwent endoscopic resection for gastric cancer by 2018. Those with severe AG or presence of IM had a significantly higher incidence of MGC than those without (RR 2.00, 95% CI 1.35-2.98, I2 = 52% for severe atrophy on antrum; RR 7.08, 95% CI 3.63-13.80, I2 = 0% for antral IM). Absolute risk difference of MGC occurrence was 7.1% in those with severe AG and 9.2% in those with IM. The difference in incidence rate per 1,000 person-years was 17.5 person-years for those with severe AG and 24.7 person-years for those with IM. However, H. pylori eradication did not significantly affect the occurrence of MGC (RR 1.18, 95% CI 0.88-1.59, I2 = 10%). CONCLUSION: Gastric cancer patients with severe AG or presence of IM had a 2.0-fold or 7.0-fold higher risk of MGC occurrence after endoscopic resection than those without, respectively. They need more stringent follow-up to monitor MGC occurrences (CRD42023410940).

On-demand Versus Continuous Maintenance Treatment With a Proton Pump Inhibitor for Mild Gastroesophageal Reflux Disease: A Prospective Randomized Multicenter Study.

Background/Aims: It remains unclear which maintenance treatment modality is most appropriate for mild gastroesophageal reflux disease (GERD). We aimed to compare on-demand treatment with continuous treatment using a proton pump inhibitor (PPI) in the maintenance treatment for patients with non-erosive GERD or mild erosive esophagitis. Methods: Patients whose GERD symptoms improved after 4 weeks of standard dose PPI treatment were prospectively enrolled at 25 hospitals. Subsequently, the enrolled patients were randomly assigned to either an on-demand or a continuous maintenance treatment group, and followed in an 8-week interval for up to 24 weeks. Results: A total of 304 patients were randomized to maintenance treatment (continuous, n = 151 vs on-demand, n = 153). The primary outcome, the overall proportion of unwillingness to continue the assigned maintenance treatment modality, failed to confirm the non-inferiority of on-demand treatment (45.9%) compared to continuous treatment (36.1%). Compared with the on-demand group, the GERD symptom and health-related quality of life scores significantly more improved and the overall satisfaction score was significantly higher in the continuous treatment group, particularly at week 8 and week 16 of maintenance treatment. Work impairment scores were not different in the 2 groups, but the prescription cost was less in the on-demand group. Serum gastrin levels significantly elevated in the continuous treatment group, but not in the on-demand group. Conclusions: Continuous treatment seems to be more appropriate for the initial maintenance treatment of non-erosive GERD or mild erosive esophagitis than on-demand treatment. Stepping down to on-demand treatment needs to be considered after a sufficient period of continuous treatment.

Impact of Autoimmune Gastritis on Occurrence of Metachronous Gastric Neoplasms after Endoscopic Resection for Gastric Neoplasms.

Gastric cancer is the fifth most common cancer and the third leading cause of cancer-related deaths worldwide. Autoimmune gastritis (AIG) is characterized by antibody production against the gastric parietal cells, reducing the number of functional parietal cells. It is also associated with an increased susceptibility to gastric neuroendocrine tumors and gastric cancer. Endoscopic resection (ER) is an effective treatment for early gastric cancer; however, metachronous gastric neoplasms (MGN) can develop. This study aimed to evaluate the clinical effect of AIG on the occurrence of MGN after ER for gastric neoplasms. We retrospectively analyzed patients who underwent ER for gastric neoplasms. Patients with multiple lesions, recurrent lesions, or a history of partial gastrectomy were excluded. The presence of AIG was determined using anti-parietal cell antibody (APCA) testing. Follow-up endoscopy and metachronous tumor occurrence rates were compared between the AIG and non-AIG groups. Of the 569 patients, 282 underwent APCA testing and 20 (7.1%) were diagnosed with AIG. The incidence of MGN was significantly higher in the AIG group than in the non-AIG group (45.0% vs. 18.3%); however, the MGN occurrence pattern was similar between the two groups. Multivariate analysis revealed that AIG (HR 3.32, 95% CI 1.55-7.10, p = 0.002) and a higher body mass index (HR 1.16, 95% CI 1.06-1.27, p = 0.002) were independent factors significantly associated with the occurrence of MGN. Patients with AIG have a higher risk of metachronous lesion occurrence after ER for gastric neoplasms. Positive results of APCA testing have independent clinical implications for predicting MGN. Proper monitoring and management are essential for early detection and treatment of recurrent lesions in patients with AIG.

Prevalence, risk factors, and treatment of small intestinal bacterial overgrowth in children.

Small intestinal bacterial overgrowth (SIBO) is defined as the presence of an excessive number of bacteria within the small bowel. Pediatric SIBO is a heterogeneous disorder that manifests as various symptoms ranging from mild gastrointestinal symptoms to malabsorption or malnutrition. The carbohydrate breath test is a commonly used, safe, and noninvasive diagnostic test; however, a standardized methodology is lacking. Multiple factors, such as neuromuscular disorders, systemic diseases, chronic drug use, or altered intestinal anatomy that disturb intestinal motility or induce an abnormality in the body's defense systems against intestinal bacteria, predispose children to SIBO. The high prevalence and similar symptoms of SIBO in functional gastrointestinal disorders, including irritable bowel syndrome, suggest an association between them. The principles of treatment include managing predisposing conditions, nutritional support, symptom control, and antibacterial treatment. Rifaximin is the most commonly used drug. To date, studies of antibiotic treatment in pediatric populations with irritable bowel syndrome or SIBO are lacking and have shown mixed results. Here we review the prevalence, diagnostic tests, and treatment results in pediatric populations.

Prevalence, natural progression, and clinical practices of upper gastrointestinal subepithelial lesions in Korea: a multicenter study.

BACKGROUND/AIMS: This study aimed to evaluate the prevalence and natural progression of subepithelial lesions (SELs) in the upper gastrointestinal (UGI) tract. METHODS: The medical records of patients with UGI SELs who underwent endoscopic screening at eight university hospitals between January and December 2010 were retrospectively investigated. The follow-up evaluations were performed until December 2016. RESULTS: UGI SELs were found in 1,044 of the 65,233 participants screened (endoscopic prevalence, 1.60%; the total number of lesions, 1,062; mean age, 55.1±11.2 years; men, 53.6%). The median follow-up period was 48 (range, 8-74) months. SELs were most frequently found in the stomach (63.8%) and had a mean size of 9.9±6.1 mm. Endoscopic ultrasonography (EUS) was performed in 293 patients (28.1%). The most common lesions were leiomyomas, followed by gastrointestinal stromal tumors (GISTs), and ectopic pancreas. The proportions of SELs with malignant potential according to size were 3% (<1 cm), 22% (1-2 cm), 27% (2-3 cm), and 38% (≥3 cm). In gastric SELs larger than 1 cm, resections were performed in 20 patients because of an increase in size, of which 12 were found to be GISTs. CONCLUSION: The prevalence of UGI SELs was 1.60%. Further, 23% of gastric SELs ≥1 cm were precancerous lesions, most followed by EUS and clinical decisions without initial pathological confirmation.

Duodenal mucosal resurfacing with photodynamic therapy using methylene blue in a mouse model.

BACKGROUND: The duodenum has emerged as a key player in metabolic diseases. The objective was to evaluate the safety and efficacy of intra-duodenal PDT using methylene blue in managing glycemic control and weight reduction. METHODS: Optimal concentration of methylene blue and conditions for intra-duodenal PDT were determined through in vitro experiments. After injecting methylene blue into the duodenum, we performed intra-duodenal PDT. High-fat diet rats were used to assess the efficacy of intra-duodenal PDT through measures of oral glucose tolerance, insulin sensitivity, and weight change. Immunohistochemical staining was also conducted to examine GLP-1 and GIP-producing cells in the ileum and duodenum, respectively. RESULTS: Introduodenal PDT reduced villous height of duodenum at 48 h, which was fully recovered at 30 days without complications. Rats treated with PDT showed significantly lower blood glucose levels with glucose loading and improved insulin sensitivity than rats in the sham-treatment group. The PDT group also had a significant reduction in body weight compared to the sham-treatment group at 30 days after intervention, although food intake was not significantly different between the two groups. Numbers of GLP-1 and GIP producing cells in the ileum and irradiated area were significantly higher in the PDT group than in the sham-treatment group. CONCLUSIONS: Intra-duodenal PDT using methylene blue showed a feasible therapeutic modality in improving metabolic parameters. However, large animal experiments and mechanism studies are needed to determine the clinical relevance. The possibility of repeating this treatment every 30 days and its accompanying complications should be further studied.

Aortic Wall Abrasion Caused by Needle Injury after Endoscopic Ultrasound-Guided Fine Needle Aspiration of a Mediastinal Hemangioma.

Benign mediastinal cysts are challenging to diagnose. Although Endoscopic Ultrasound (EUS) and EUS-guided fine needle aspiration (FNA) can accurately diagnose mediastinal foregut cysts, little is known about their complications. This paper reports a rare case in which EUS-FNA performed on mediastinal hemangioma resulted in an aortic hematoma. A 29-year-old female patient was commissioned for EUS of an asymptomatic accidental mediastinal lesion. Chest CT revealed a 4.9×2.9×10.1 cm thin-walled cystic mass in the posterior mediastinum. EUS revealed a large, anechoic cystic lesion with a regular thin wall with negative Doppler. EUS-guided FNA was performed using a single-use 19-gauge aspiration needle (EZ Shot 3; Olympus, Tokyo, Japan), and approximately 70 cc of serous pinkish fluid was aspirated. The patient was in a stable condition with no signs of acute complication. One day after EUS-FNA, thoracoscopic resection for mediastinal mass was conducted. The purple and multi-loculated large cyst was removed. Upon removal, however, an aortic hematoma caused by a focal descending aortic wall injury was observed. After a few days of close observation, the patient was discharged upon stable 3D aorta angio CT findings. This paper reports a rare and severe complication of EUS-FNA, in which an aspiration needle caused a direct injury to the aorta. The injection must be performed carefully to avoid damaging the adjacent organs or digestive tract walls.

Hypercontractile Esophagus: Clinical and Manometric Features From a Multicenter Korean Cohort.

Background/Aims: Hypercontractile esophagus (HE) is a heterogeneous disorder with variable clinical presentations and a natural course, leading to management challenges. This study aims to investigate the characteristics of HE and evaluate its treatment outcomes. Methods: Four Korean referral centers recruited subjects with at least 1 hypercontractile swallow (distal contraction integral > 8000 mmHg·s·cm) in this retrospective observational study. Subjects were classified according to the Chicago classification version 2.0 (CC v2.0), CC v3.0, and CC v4.0. criteria. The clinical and manometric features were also investigated. The treatment modalities and outcomes of subjects with CC v4.0 were evaluated. Results: In total, 59 subjects with at least 1 hypercontractile swallow were analyzed. Among them, 30 (50.8%) had increased integrated relaxation pressure values without meeting the criteria for achalasia. Among the remaining 29 patients, 6 (20.7%) had only 1 hypercontractile swallowing symptom (CC v2.0) and 23 (79.3%) met both the CC v3.0 and v4.0 criteria for HE. Dysphagia (91.3%) was the most prevalent symptom, followed by chest pain (56.5%), regurgitation (52.2%), globus (34.8%), heartburn (21.7%), and belching (8.7%). Twenty (87.0%) patients received medical treatment, and 8 (47.1%) and 5 (29.4%) showed moderate and significant improvements, respectively. Proton pump inhibitors were the most common option (n = 15, 65.2%), followed by calcium channel blockers (n = 6, 26.1%). One patient received peroral endoscopic myotomy and showed significant symptom improvement. Conclusions: Sixty-one percent of patients who meet the diagnostic criteria for the high-resolution manometry are diagnosed with symptomatic HE based CC v4.0. Chest pain and regurgitation were also observed in over half of them. The overall medical treatment efficacy was moderate.

Accuracy of administrative claim data for gastric adenoma after endoscopic resection.

BACKGROUND/AIMS: Administrative databases provide valuable information for large-cohort studies. This study aimed to evaluate the diagnostic accuracy of an administrative database for resected gastric adenomas. METHODS: Data of patients who underwent endoscopic resection for benign gastric lesions were collected from three hospitals. Gastric adenoma cases were identified in the hospital database using International Classification of Diseases (ICD) 10-codes. The non-adenoma group included patients without gastric adenoma codes. The diagnostic accuracy for gastric adenoma was analyzed based on the pathological reports of the resected specimen. RESULTS: Among 5,095 endoscopic resections with codes for benign gastric lesions, 3,909 patients were included in the analysis. Among them, 2,831 and 1,078 patients were allocated to the adenoma and non-adenoma groups, respectively. Regarding the overall diagnosis of gastric adenoma with ICD-10 codes, the sensitivity, specificity, positive predictive value, and negative predictive value were 98.7%, 88.5%, 95.2%, and 96.8%, respectively. There were no significant differences in these parameters between the tertiary and secondary centers. CONCLUSION: Administrative codes of gastric adenoma, according to ICD-10 codes, showed good accuracy and can serve as a useful tool to study prognosis of these patients in real-world data studies in the future.

Tumor heterogeneity and carcinoma in resected specimens of gastric low-grade dysplasia: A retrospective single center study.

Lesions diagnosed as gastric low-grade dysplasia (LGD) may be pathologically upgraded to early gastric cancer (EGC) or high-grade dysplasia (HGD) after endoscopic resection (ER). In this study, we investigated the risk factors for pathological upgrades after ER and assessed the reason for these upgrades by retrospectively analyzing ER data between January 1999 and December 2019. We enrolled patients with LGD confirmed by forceps biopsy; the patients were classified into pathologically concordant (LGD) and upgraded (HGD and EGC) groups according to the pathology of their resected specimen. To determine the risk factors for upgrade, we compared the endoscopic findings of the concordant and upgraded groups via 1:1 matched case-control design. To find the reasons for discordance, all upgraded cases were pathologically re-evaluated. Among 1,643 cases of LGD, pathological upgrades were observed in 423 (25.7%) resected specimens and EGC was found in 111 (6.7%) lesions. After matching the upgraded and concordant cases, lesion sizes exceeding 1.5 cm (odds ratio (OR): 1.8; 95% CI: 1.1-3.0), mucosal nodularity (OR: 10.8; 95% CI: 5.6-21.0), heterogeneous color (OR: 3.0; 95% CI: 1.7-5.3), presence of erosion (OR: 2.7; 95% CI: 1.8-5.3), and open-type gastric atrophy (OR: 2.9; 95% CI: 1.7-4.9) were noted to be significantly associated with upgraded pathology to EGC. Among the EGC cases, 99 (89.2%) were found to have pre-existing dysplasia. In conclusion, endoscopic evaluations should be performed because of possible pathological upgrades and co-existence of carcinomas in LGDs, especially when they exhibit surface nodularity, erosion, heterogeneous color, and large size.

Randomised clinical trial: comparison of tegoprazan and lansoprazole as maintenance therapy for healed mild erosive oesophagitis.

BACKGROUND: Tegoprazan is a novel potassium-competitive acid blocker used to treat acid-related disorders. AIM: To compare tegoprazan 25 mg with lansoprazole 15 mg as maintenance therapy in healed erosive oesophagitis (EE) METHODS: In this phase 3, double-blind, multi-centre study, patients with endoscopically confirmed healed EE were randomised 1:1 to receive tegoprazan 25 mg or lansoprazole 15 mg once daily for up to 24 weeks. The primary efficacy endpoint was the endoscopic remission rate after 24 weeks. The secondary efficacy endpoint was the endoscopic remission rate after 12 weeks. Safety endpoints included adverse events, clinical laboratory results and serum gastrin and pepsinogen I/II levels. RESULTS: We randomised patients to tegoprazan 25 mg (n = 174) or lansoprazole 15 mg (n = 177). Most had mild EE (Los Angeles (LA) grade A: 57.3%, LA grade B: 37.3%). The endoscopic remission rate after 24 weeks was 90.6% with tegoprazan and 89.5% with lansoprazole. Tegoprazan was not inferior to lansoprazole for maintaining endoscopic remission at 24 weeks and 12 weeks. In subgroup analysis, tegoprazan 25 mg showed no significant difference in maintenance rate according to LA grade (p = 0.47). The maintenance effect of tegoprazan was consistent in CYP2C19 extensive metabolisers (p = 0.76). Increases in serum gastrin were not higher in tegoprazan-treated than lansoprazole-treated patients. CONCLUSIONS: Tegoprazan 25 mg was non-inferior to lansoprazole 15 mg in maintenance of healing of mild EE. In this study, tegoprazan had a similar safety profile to lansoprazole.

Efficacy of bougie dilation for normal diet in benign esophageal stricture.

OBJECTIVES: Bougination is one of the first-line treatments in benign esophageal stricture (BES). The aim of the study was to identify clinical and endoscopic factors affecting the achievement of a normal diet with only bougie dilation in patients with BES. PATIENTS AND METHODS: Patients treated with only bougination for BES at three hospitals were retrospectively investigated. Data including patient demographics, stricture and procedural characteristics were collected. Clinical success was defined as normal diet without additional procedures for two months after bougination. Clinical success rate and associated factors were assessed. RESULTS: A total of 121 patients with BES were included. The most common cause of BES was post-operative stricture (n = 55). Finally, 43 (36%) patients were able to eat a normal diet with only bougination. Of these patients, 42 (97.7%) achieved clinical success in the first three sessions or less. Among causes of stenosis, corrosive injury had the lowest success rate (9/40, 22.5%). Clinical success rate was significantly higher for those with the length of stricture of less than 2 cm (47.2%), those with pre-procedural dysphagia of semi-solid or soft diet (51.3%) and those with dilation of 13 mm or more (46.1%). However, the duration of symptom, the number of previous endoscopic treatments and the location of stenosis were not related to clinical success. CONCLUSIONS: Normal diet is possible in one-third of BES after bougination alone. Predictable factors for achieving a normal diet were less than four sessions of dilation, short length of stricture, pre-procedural dysphagia status and diameter of dilator.

Collagenous Gastoduodenitis in the Form of a Gastric Ulcer.

Collagenous gastroduodenitis is a rare gastrointestinal disease diagnosed histologically by subepithelial collagen deposition in the lamina propria. Its clinical presentation is diverse. The authors encountered a 17-year-old female patient who complained of epigastric pain. Endoscopy revealed several deep ulcers in the gastric body. The gastric mucosa around the ulcer showed diffuse fine nodularity in the shape of cobblestones with open-type atrophy. The duodenal mucosa showed nodular lesions similar to those of the gastric mucosa. The gastric ulcer healed completely with proton pump inhibitor treatment. The patient was followed up, showing no remarkable mucosal change of stomach or duodenum for several years. Collagenous gastroduodenitis was diagnosed by repeated histologic examinations. This paper reports a rare case of chronic collagen gastritis with deep gastric ulcer and its long-term clinical progress.

Combined high NEDD9 expression and E-cadherin loss correlate with poor clinical outcome in gastric cancer.

BACKGROUND AND AIM: Neural precursor cell expressed developmentally downregulated 9 (NEDD9) is a member of the Cas family. Previous studies have revealed that NEDD9 coordinates the focal adhesion kinase and Src signaling cascades that are involved in integrin-dependent adhesion and migration, invasion, cell apoptosis and life cycle, and survival, which may play a role in epithelial-mesenchymal transformation. The aim of this study was to analyze the expression of NEDD9 and E-cadherin in gastric cancer (GC) and evaluate their clinical significance. METHODS: NEDD9 and E-cadherin expression was analyzed with immunohistochemistry using tissue microarray technique in 435 GC patients who underwent gastrectomy. The NEDD9 expression level was defined by the combination score, which was determined by multiplying the staining intensity score and the proportion score (≥5; NEDD9-high, <5; NEDD9-low). E-cadherin loss was defined as a total loss of staining. The clinicopathologic parameters, overall survival, and disease-free survival rates were analyzed according to the NEDD9 and E-cadherin expression status. RESULTS: The combined NEDD9 and E-cadherin expression status correlated with lymphatic invasion (P = 0.001), vascular invasion (P = 0.020), and T stage (P = 0.001). Combined high NEDD9 expression and loss of E-cadherin expression status had a worse overall survival rate (P < 0.001) and served as a poor prognostic factor (Hazard ratio 2.49, 95% CI 1.25-5, P = 0.01). CONCLUSIONS: Immunohistochemical staining for NEDD9 and E-cadherin may function as a candidate prognostic marker for gastric cancer in everyday practice, especially when applied in combination.