Highly functional duodenal stent with photosensitizers enables photodynamic therapy for metabolic syndrome treatment: Feasibility and safety study in a porcine model.

Duodenal mucosal resurfacing (DMR) by thermal ablation of the duodenal mucosa is a minimally invasive endoscopic procedure for controlling metabolic syndrome (MS). However, thermal energy can cause adverse effects due to deep mucosal injury, necessitating an additional mucosal lifting process, which complicate the procedures. Therefore, we aimed to develop a similar procedure using non-thermal photodynamic therapy (PDT) for DMR using a highly functional metal stent covered with photosensitizers (PSs) to minimize the potential risks of thermal ablation injury. We developed a novel PS stent enabling the controlled release of radical oxygen species with specific structures to prevent stent migration and duodenal stricture after ablation and performed an animal study (n = 8) to demonstrate the feasibility and safety of PDT for DMR. The stents were placed for 7 days to prevent duodenal strictures after PDT. To confirm PDT efficacy, we stained for gastric inhibitory polypeptide (GIP) and glucose transporter isoform 1. The PS stents were deployed, and PDT was applied without evidence of duodenal stricture, pancreatitis, or hemorrhage in any of the pigs. Microscopic evaluation indicated apoptosis of the mucosal cells in the irradiated duodenum on days 7 and 14, which recovered after day 28. Immunohistochemistry revealed suppressed GIP expression in the mucosal wall of the irradiated duodenum. Endoscopic PDT for DMR using PS stents could be applied safely in a porcine model and may result in decreased GIP secretion, which is a crucial mechanism in MS treatment. Further clinical studies are required to explore its safety and efficacy in patients with MS.

Prognostic Impact of Inflammation-Based Factors in Patients with Esophageal Squamous Cell Carcinoma Achieving Pathological Complete Response After Neoadjuvant Chemoradiotherapy Followed by Surgery.

BACKGROUND: Patients achieving pathological complete response (pCR) post-neoadjuvant chemoradiotherapy (nCRT) and surgery for locally advanced esophageal squamous cell carcinoma (ESCC) have a favorable prognosis. However, recurrence occurs in approximately 20-30% of all patients, with few studies evaluating their prognostic factors. We identified these prognostic factors, including inflammation-based markers, in patients with ESCC showing pCR after nCRT and surgery. PATIENTS AND METHODS: Patients with ESCC undergoing esophagectomy post-nCRT (January 2007-August 2017) were studied. Survival analysis evaluated 5-year overall (OS) and recurrence-free survival (RFS). Risk factors, including inflammation factors, neutrophil-to-lymphocyte ratio, and platelet-to-lymphocyte ratio (PLR), were analyzed using Cox-proportional hazards model. RESULTS: Overall, 123patients participated herein. After a median follow-up duration of 67 months (44-86 months), 17 patients (12.3%) had recurrent disease. The 5-year OS and RFS rates were 71.6% and 68.0%, respectively. In the multivariable analysis, older age ( ≥ 60 years) [hazard ratio (HR) 3.228, 95% confidence interval (CI) 1.478-7.048, p = 0.003], higher pretreatment T stage (≥ T3; HR 2.563, 95% CI 1.335-4.922, p = 0.005), nonapplication of induction chemotherapy (HR 2.389, 95% CI 1.184-4.824, p = 0.015), and higher post-nCRT PLR (≥ 184.2; HR 2.896, 95% CI 1.547-5.420, p = 0.001) were poor independent prognostic factors for 5-year RFS. The patient group with three to four identified factors with poor outcomes exhibited a 5-year RFS rate of 46.2%. CONCLUSIONS: Significant prognostic factors include higher post-nCRT PLR, older age, higher clinical T stage, and nonapplication of induction chemotherapy. Identifying higher recurrence risk patients is crucial for tailored follow-up and treatment.

Randomized, Double-blind, Active-controlled Phase 3 Study to Evaluate Efficacy and Safety of Zastaprazan compared to Esomeprazole in Erosive Esophagitis.

INTRODUCTION: Zastaprazan is a potent potassium-competitive acid blocker (P-CAB) developed to treat gastroesophageal reflux disease. This study aims to evaluate the efficacy and safety of zastaprazan compared to esomeprazole in patient with erosive esophagitis (EE). METHODS: A phase III, multicenter, randomized, double-blind, non-inferiority clinical study was conducted with 300 subjects with confirmed EE. Subjects were randomized to receive zastaprazan 20 mg or esomeprazole 40 mg once daily up to 8 weeks. The primary endpoint was the cumulative proportion of subject with healed EE confirmed by endoscopy at week 8. The secondary endpoints included the healing rate at week 4, symptom response and quality of life assessment. Safety profiles and serum gastrin levels were also assessed. RESULTS: In the full analysis set, the cumulative healing rate at week 8 were 97.92% (141/144) for zastaprazan and 94.93% (131/138) (P = 0.178) for esomeprazole. The healing rate at week 4 in the zastaprazan group was higher than esomeprazole group (95.14% (137/144) vs. 87.68% (121/138); P = 0.026). There was no significant difference between groups in healing rates (the per-protocol set) at week 8 and week 4, symptom responses, quality of life assessments and safety profiles. In addition, serum gastrin levels increased during treatment in both groups, with a significant difference between the two groups (P = 0.047), but both decreased after treatment. DISCUSSION: An 8-week therapy of zastaprazan 20 mg is non-inferior to esomeprazole 40 mg in subjects with predominantly low-grade EE. The healing rate at week 4 appears to be higher for zastaprazan than esomeprazole.

Culture-based susceptibility-guided tailored versus empirical concomitant therapy as first-line Helicobacter pylori treatment: A randomized clinical trial.

BACKGROUND: With the increasing resistance to antimicrobial agents, susceptibility-guided tailored therapy has been emerging as an ideal strategy for Helicobacter pylori treatment. However, susceptibility-guided tailored therapy requires additional cost, time consumption, and invasive procedure (endoscopy) and its superiority over empirical quadruple therapy as the first-line H. pylori treatment remains unclear. AIMS: To compare the efficacy of culture-based susceptibility-guided tailored versus empirical concomitant therapy as the first-line Helicobacter pylori treatment. METHODS: This open-label, randomized trial was performed in four Korean institutions. A total of 312 Patients with H. pylori-positive culture test and naïve to treatment were randomly assigned in a 3:1 ratio to either culture-based susceptibility-guided tailored therapy (clarithromycin-based or metronidazole-based triple therapy for susceptible strains or bismuth quadruple therapy for dual-resistant strains, n = 234) or empirical concomitant therapy (n = 78) for 10 days. Eradication success was evaluated by 13C-urea breath test at least 4 weeks after treatment. RESULTS: Prevalence of dual resistance to both clarithromycin and metronidazole was 8%. H. pylori eradication rates for tailored and concomitant groups were 84.2% and 83.3% by intention-to-treat analysis (p = 0.859), respectively, and 92.9% and 91.5% by per-protocol analysis, respectively (p = 0.702), which were comparable between the two groups. However, eradication rates for dual-resistant strains were significantly higher in the tailored group than in the concomitant group. All adverse events were grade 1 or 2 based on the Common Terminology Criteria for Adverse Events and the incidence was significantly lower in the tailored group. The proportion of patients discontinuing treatment for adverse events was comparable between the two groups (2.1% vs. 2.6%). CONCLUSIONS: The culture-based susceptibility-guided tailored therapy failed to show superiority over the empirical concomitant therapy in terms of eradication rate. Based on these findings, the treatment choice in clinical practice would depend on the background rate of antimicrobial resistance, availability of resources and costs associated with culture and susceptibility testing.

Clinical course of asymptomatic duodenal subepithelial lesions.

BACKGROUND/AIMS: There is limited knowledge regarding the management of duodenal subepithelial lesions (SELs) owing to a lack of understanding of their natural course. This study aimed to assess the natural course of asymptomatic duodenal SELs and provide management recommendations. METHODS: Patients diagnosed with duodenal SELs and followed up for a minimum of 6 months were retrospectively investigated. RESULTS: Among the 443,533 patients who underwent esophagogastroduodenoscopy between 2008 and 2020, duodenal SELs were identified in 0.39% (1,713 patients). Among them, 396 duodenal SELs were monitored for a median period of 72.5 months (interquartile range, 37.7-111.3 mo). Of them, 16 SELs (4.0%) showed substantial changes in size or morphology at a median follow-up of 35.1 months (interquartile range, 21.7-51.4 mo). Of these SELs with substantial changes, tissues of two SELs were acquired using endoscopic ultrasound-guided fine needle aspiration biopsy: one was a lipoma and the other was non-diagnostic. Three SELs were surgically or endoscopically removed; two were diagnosed as gastrointestinal stromal tumors, and one was a lipoma. An initial size of 20 mm or larger was associated with substantial changes during follow-up (p = 0.016). CONCLUSION: While the majority of duodenal SELs may not exhibit substantial interval changes, regular follow-up with endoscopy may be necessary for cases with an initial size of 20 mm or larger, considering a possibility of malignancy.

Association of local steroid injection as a risk factor for electrocoagulation syndrome after esophageal endoscopic submucosal dissection.

BACKGROUND: Postendoscopic submucosal dissection electrocoagulation syndrome (PEECS) is commonly observed after performing endoscopic submucosal dissection (ESD) for esophageal neoplasia. However, data on the incidence and risk factors for PEECS in the esophagus are lacking due to an unclear definition of PEECS and varied clinical settings. Therefore, we aimed to determine the risk factors for PEECS in patients undergoing ESD for esophageal neoplasia. METHODS: We retrospectively reviewed data of relevant clinical and endoscopy-specific parameters from 202 consecutive patients with esophageal neoplasias (139 carcinomas and 63 dysplasias) who underwent ESD under general anesthesia. Esophageal PEECS was defined by satisfying at least two of the following criteria: fever ≥ 37.8 °C, leukocytosis ≥ 10,800/mm3, and localized chest pain ≥ 5/10 points as assessed on a numeric rating scale within 24 h after ESD. Significant factors associated with PEECS were determined by regression analysis. RESULTS: PEECS was recorded in 98 of 202 (48.5%) patients. Patients with PEECS exhibited a larger tumor size (25.0 vs. 17.0 mm, P = 0.002), longer procedure (40.0 vs. 29.5 min, P = 0.021) and hemostasis times (5.0 vs. 3.5 min, P = 0.004), required greater submucosal injection volume (60.0 mL vs. 50.0 mL, P = 0.030), and had a lower rate of local steroid injection (4.1% vs. 12.5%, P = 0.029) than those without PEECS. Multivariate regression analysis revealed tumor size ≥ 17 mm (P = 0.047), procedure time ≥ 33 min (P = 0.027), and hemostasis time ≥ 5 min (P = 0.007) as risk factors for PEECS. In addition, local steroid injection was a significant negatively associated factor (P = 0.001). CONCLUSIONS: Patients with a large tumor, prolonged procedure and hemostasis times are at a high risk of PEECS occurrence. Further, local steroid injection is a negatively associated factor.

Predicting Helicobacter pylori infection from endoscopic features.

BACKGROUND: Helicobacter pylori infection, prevalent in more than half of the global population, is associated with various gastrointestinal diseases, including peptic ulcers and gastric cancer. The effectiveness of early diagnosis and treatment in preventing gastric cancer highlights the need for improved diagnostic methods. This study aimed to develop a simple scoring system based on endoscopic findings to predict H. pylori infection. METHODS: A retrospective analysis was conducted on 1,007 patients who underwent upper gastrointestinal endoscopy at Asan Medical Center from January 2019 to December 2021. Exclusion criteria included prior H. pylori treatment, gastric surgery, or gastric malignancies. Diagnostic techniques included rapid urease and 13C-urea breath tests, H. pylori culture, and assessment of endoscopic features following the Kyoto gastritis classification. A new scoring system based on endoscopic findings including regular arrangement of collecting venules (RAC), nodularity, and diffuse or spotty redness was developed for predicting H. pylori infection, utilizing logistic regression analysis in the development set. RESULTS: The scoring system demonstrated high predictive accuracy for H. pylori infection in the validation set. Scores of 2 and 3 were associated with 96% and 99% infection risk, respectively. Additionally, there was a higher prevalence of diffuse redness and sticky mucus in cases where the initial H. pylori eradication treatment failed. CONCLUSION: Our scoring system showed potential for improving diagnostic accuracy in H. pylori infection. H. pylori testing should be considered upon spotty redness, diffuse redness, nodularity, and RAC absence on endoscopic findings as determined by the predictive scoring system.

Repeated photodynamic therapy using a chlorin e6-embedded device to prolong the therapeutic effects on obesity.

OBJECTIVE: This study aimed to investigate the efficacy and safety of repeated photodynamic therapy (PDT) with a chlorin e6 (Ce6)-embedded intragastric satiety-inducing device (ISD) to maintain therapeutic effects of obesity in a juvenile pig. METHODS: The Ce6-embedded ISD was fabricated with a dipping method. Twelve pigs were divided into four groups of three and were administered control, single, biweekly, or weekly PDT, respectively. The therapeutic effects were assessed by comparing the results of phototoxicity, endoscopy, fluoroscopy, hormone and weight changes, and histological examination. RESULTS: The percentage of total body weight gain was significantly suppressed in PDT-treated pigs compared with control pigs (all p < 0.001). This suppression persisted in the repeated PDT groups, but percentage of total body weight gain gradually increased when PDT was stopped. Ghrelin levels in the PDT-treated groups were significantly lower and leptin levels were significantly higher than those in the control group (all p < 0.05). Inflammatory cell infiltration, collagen, TUNEL, and anti-ghrelin-positive deposition in the weekly group were significantly higher than those in the control, single, and biweekly groups (all p < 0.01). CONCLUSIONS: Repeated and periodic PDT was technically feasible and safe and successfully maintained the therapeutic effects against obesity while eliminating the indwelling time and reducing ISD-related complications in pigs.

Endoscopic resection of gastric gastrointestinal stromal tumor using clip-and-cut endoscopic full-thickness resection: a single-center, retrospective cohort in Korea.

BACKGROUND/AIMS: To overcome the technical limitations of classic endoscopic resection for gastric gastrointestinal stromal tumors (GISTs), various methods have been developed. In this study, we examined the role and feasibility of clip-and-cut procedures (clip-and-cut endoscopic full-thickness resection [cc-EFTR]) for gastric GISTs. METHODS: Medical records of 83 patients diagnosed with GISTs after endoscopic resection between 2005 and 2021 were retrospectively reviewed. Moreover, clinical characteristics and outcomes were analyzed. RESULTS: Endoscopic submucosal dissection (ESD) and cc-EFTR were performed in 51 and 32 patients, respectively. The GISTs were detected in the upper third of the stomach for ESD (52.9%) and cc-EFTR (90.6%). Within the cc-EFTR group, a majority of GISTs were located in the deep muscularis propria or serosal layer, accounting for 96.9%, as opposed to those in the ESD group (45.1%). The R0 resection rates were 51.0% and 84.4% in the ESD and cc-EFTR groups, respectively. Seven (8.4%) patients required surgical treatment (six patients underwent ESD and one underwent cc-EFTR,) due to residual tumor (n=5) and post-procedure adverse events (n=2). Patients undergoing R0 or R1 resection did not experience recurrence during a median 14-month follow-up period, except for one patient in the ESD group. CONCLUSIONS: cc-EFTR displayed a high R0 resection rate; therefore, it is a safe and effective therapeutic option for small gastric GISTs.

Dysphagia associated with esophageal wall thickening in patients with nonspecific high-resolution manometry findings: Understanding motility beyond the Chicago classification version 4.0.

BACKGROUND: Previous studies have demonstrated that 50% of patients with normal high-resolution manometry (HRM) findings or ineffective esophageal motility (IEM) may have abnormal functional luminal imaging probe (FLIP) results. However, the specific HRM findings associated with abnormal FLIP results are unknown. Herein, we investigated the relationship between nonspecific manometry findings and abnormal FLIP results. METHODS: We retrospectively analyzed 684 patients who underwent HRM at a tertiary care center in Seoul, Korea, based on the Chicago Classification version 4.0 protocol. KEY RESULTS: Among the 684 patients, 398 had normal HRM findings or IEM. Of these 398 patients, eight showed esophageal wall thickening on endoscopic ultrasonography or computed tomography; however, no abnormalities were seen during esophagogastroduodenoscopy. Among these eight patients, seven showed repetitive simultaneous contractions (RSCs) in at least one of the two positions: 61% (±29%) in 10 swallows in the supine position and 51% (±30%) in five swallows in the upright position. Four patients who underwent FLIP had a significantly decreased esophagogastric junction distensibility index (1.0 ± 0.5 m m 2 mmHg - 1 at 60 mL). Two of these patients underwent per-oral endoscopic myotomy (POEM) due to a lack of response to medication. Esophageal muscle biopsy revealed hypertrophic muscle with marginal eosinophil infiltration. CONCLUSIONS & INFERENCES: A subset of patients (2%) with normal HRM findings or IEM and RSCs experienced dysphagia associated with poor distensibility of the thickened esophageal wall. FLIP assessment or combined HRM and impedance protocols may help better define these patients who may respond well to POEM.

Clinical outcomes of argon plasma coagulation for the treatment of gastric low-grade dysplasia.

BACKGROUND AND AIMS: Argon plasma coagulation (APC) could be considered a treatment modality for small gastric low-grade dysplasia (LGD) instead of endoscopic resection. Our study investigated the clinical outcomes of APC for treating gastric LGD and associated variables with local recurrence. METHODS: This study included 911 patients who underwent APC for gastric neoplasms at the tertiary hospital from July 2007 to March 2022 with a minimal follow-up of 12 months. Of these patients, 112 without any information about Helicobacter pylori infection status, 164 who underwent APC for salvage therapy, 5 with high-grade dysplasia, and 12 with cancer were excluded. Through a retrospective review of medical data, the clinical outcomes and variables associated with the local recurrence were analyzed. RESULTS: A total of 618 patients with LGD (median age, 64 years) were followed up for a median of 30 months, and local recurrence has happened in 21 (3.4%) patients. Multivariate analysis showed that lesion size (hazard ratio, 1.06; 95% confidential interval, 1.01-1.12) was associated with the local recurrence. Among 557 lesions smaller than 10 mm, local recurrence was found in 14 (2.6%) cases, and local recurrence was found in 7 (9.5%) cases of 109 tumors larger than 10 mm (P < .004). CONCLUSIONS: In gastric LGD smaller than 10 mm without scars, APC is a good treatment modality in place of endoscopic resection. However, when a lesion is larger, APC should be selected carefully with close monitoring.

Evaluation of the Efficacy and Safety of DW1903 in Patients with Gastritis: A Randomized, Double-Blind, Noninferiority, Multicenter, Phase 3 study.

Background/Aims: H2 receptor antagonists (H2RA) have been used to treat gastritis by inhibiting gastric acid. Proton pump inhibitors (PPIs) are more potent acid suppressants than H2RA. However, the efficacy and safety of low-dose PPI for treating gastritis remain unclear. The aim was to investigate the efficacy and safety of low-dose PPI for treating gastritis. Methods: A double-blind, noninferiority, multicenter, phase 3 clinical trial randomly assigned 476 patients with endoscopic erosive gastritis to a group using esomeprazole 10 mg (DW1903) daily and a group using famotidine 20 mg (DW1903R1) daily for 2 weeks. The full-analysis set included 319 patients (DW1903, n=159; DW1903R1, n=160) and the per-protocol set included 298 patients (DW1903, n=147; DW1903R1, n=151). The primary endpoint (erosion improvement rate) and secondary endpoint (erosion and edema cure rates, improvement rates of hemorrhage, erythema, and symptoms) were assessed after the treatment. Adverse events were compared. Results: According to the full-analysis set, the erosion improvement rates in the DW1903 and DW1903R1 groups were 59.8% and 58.8%, respectively. According to the per-protocol analysis, the erosion improvement rates in the DW1903 and DW1903R1 groups were 61.9% and 59.6%, respectively. Secondary endpoints were not significantly different between two groups except that the hemorrhagic improvement rate was higher in DW1903 with statistical tendency. The number of adverse events were not statistically different. Conclusions: DW1903 of a low-dose PPI was not inferior to DW1903R1 of H2RA. Thus, lowdose PPI can be a novel option for treating gastritis (ClinicalTrials.gov Identifier: NCT05163756).

Efficacy and safety of HIP1601 (dual delayed-release esomeprazole) 40 mg in erosive esophagitis compared to HGP1705 (delayed-release esomeprazole) 40 mg: a multicenter, randomized, double-blind, non-inferiority study.

BACKGROUND: Proton-pump inhibitors (PPIs) are the most effective drugs for treating acid-related disorders. However, once-daily dosing with conventional PPIs fail to fully control acid secretion over 24 h. This study aimed to compare the efficacy and safety of HIP1601 (dual delayed-release esomeprazole) and HGP1705 (delayed-release esomeprazole) in patients with erosive esophagitis (EE). METHODS: We enrolled 213 patients with EE randomized in a 1:1 ratio to receive 40 mg HIP1601 (n = 107) or HGP1705 (n = 106) once daily for 4 or 8 weeks. The primary endpoint was the EE healing rate, confirmed by endoscopy up to week 8. GERD-related symptoms and treatment-emergent adverse events were compared between both groups. RESULTS: By week 8, the estimated healing rates of EE were 97.8% and 96.8% in the HIP1601 and HGP1705 groups, respectively, with a 95% confidence interval of -4.7 to 7.2. After 4 or 8 weeks of treatment, the EE healing rate at week 4, complete resolution rate of symptoms, time to sustained resolution of symptoms, and number of rescue medications used were similar in both groups. The proportion of heartburn- and acid regurgitation-free nights by week 4 were higher in the HIP1601 group compared to the HGP1705 group, but the difference did not reach clinical significance (87.7% vs. 85.8%, P = 0.514, 87.5% vs. 85.8%, P = 0.774). The number of adverse events did not differ significantly between the two groups. CONCLUSIONS: The efficacy and safety of HIP1601 40 mg were comparable to those of HGP1705 40 mg for the treatment of EE and symptomatic improvement of GERD. TRIAL REGISTRATION: NCT04080726 ( https://classic. CLINICALTRIALS: gov/ct2/show/NCT04080726 ), registration date: 25/10/2018.

Differential Diagnosis of Thickened Gastric Wall between Hypertrophic Gastritis and Borrmann Type 4 Advanced Gastric Cancer.

Background/Aims: : Accurately diagnosing diffuse gastric wall thickening is challenging. Hypertrophic gastritis (HG), while benign, mimics the morphology of Borrmann type 4 advanced gastric cancer (AGC B-4). We compared the features of endoscopy and endoscopic ultrasonography (EUS) between them. Methods: : We retrospectively reviewed patients who underwent EUS for gastric wall thickening between 2000 and 2021, selecting HG and pathologically confirmed advanced gastric cancer cases. Ulceration and antral wall thickening were determined via endoscopy, while EUS assessed the 5-layered gastric wall structure, measuring the proper muscle (PM) layer and total wall thickness. Results: : Male dominance was observed in AGC B-4, and the hemoglobin and albumin levels were significantly lower. The rate of antral wall thickening and presence of ulceration were significantly higher in AGC B-4 cases. Destruction of the PM layers was observed only in AGC B-4 cases, and the PM was significantly thicker in AGC B-4 cases. Forceps biopsy had an excellent success rate in ulcer-present AGC B-4 cases, but only a 42.6% success rate was observed for cases without ulcers, necessitating additional diagnostic modalities. A PM thickness of 2.39 mm distinguished between AGC B-4 and HG effectively. The multivariable analysis showed that a thickened PM layer and the presence of ulceration were significant risk factors for the diagnosis of AGC B-4. Conclusions: : Endoscopic findings of a thickened gastric wall, including antral involvement, and presence of ulcer were significant risk factors for the diagnosis of AGC B-4. EUS findings of destroyed wall layers and a thickened PM of >2.39 mm were the key points of differentiation between HG and AGC B-4.

Adult-onset megacolon with focal hypoganglionosis: A detailed phenotyping and prospective cohort study.

BACKGROUND: In this prospective cohort study, we evaluated features of "adult-onset megacolon with focal hypoganglionosis." METHODS: We assessed the radiologic, endoscopic, and histopathologic phenotyping and treatment outcomes of 29 patients between 2017 and 2020. Data from community controls, consisting of 19,948 adults undergoing health screenings, were analyzed to identify risk factors. Experts reviewed clinical features and pathological specimens according to the London Classification for gastrointestinal neuromuscular pathology. KEY RESULTS: The median age of the patients with adult-onset megacolon with focal hypoganglionosis at symptom onset was 59 years (range, 32.0-74.9 years), with mean symptom onset only 1 year before diagnosis. All patients had focal stenotic regions with proximal bowel dilatation (mean diameter, 78.8 mm; 95% confidence interval [CI], 72-86). The comparison with community controls showed no obvious risk factors. Ten patients underwent surgery, and all exhibited significant hypoganglionosis: 5.4 myenteric ganglion cells/cm (interquartile range [IQR], 3.7-16.4) in the stenotic regions compared to 278 cells/cm (IQR, 190-338) in the proximal and 95 cells/cm (IQR, 45-213) in the distal colon. Hypoganglionosis was associated with CD3+ T cells along the myenteric plexus. Colectomy was associated with significant symptom improvement compared to medical treatment [change in the Global Bowel Satisfaction score, -5.4 points (surgery) vs. -0.3 points (medical treatment); p < 0.001]. CONCLUSIONS AND INFERENCES: Adult-onset megacolon with focal hypoganglionosis has distinct features characterized by hypoganglionosis due to inflammation. Bowel resection appears to benefit these patients.

Comparison of Diagnosis of Esophageal Motility Disorders by Chicago Classification Versions 3.0 and 4.0.

Background/Aims: We aim to investigate the diagnostic accuracy and differences between Chicago classification version 3.0 (CC v3.0) and 4.0 (CC v4.0). Methods: Patients who underwent high-resolution esophageal manometry (HRM) for suspected esophageal motility disorders were prospectively recruited between May 2020 and February 2021. The protocol of HRM studies included additional positional change and provocative testing designed by CC v4.0. Results: Two hundred forty-four patients were included. The median age was 59 (interquartile range, 45-66) years, and 46.7% were males. Of these, 53.3% (n = 130) and 61.9% (n = 151) were categorized as normalcy by CC v3.0 and CC v4.0, respectively. The 15 patients diagnosed of esophagogastric junction outflow obstruction (EGJOO) by CC v3.0 was changed to normalcy by position (n = 2) and symptom (n = 13) by CC v4.0. In seven patients, the ineffective esophageal motility (IEM) diagnosis by CC v3.0 was changed to normalcy by CC v4.0. The diagnostic rate of achalasia increased from 11.1% (n = 27) to 13.9% (n = 34) by CC v4.0. Of patients diagnosed IEM by CC v3.0, 4 was changed to achalasia based on the functional lumen imaging probe (FLIP) results by CC v4.0. Three patients (2 with absent contractility and 1 with IEM in CC v3.0) were newly diagnosed with achalasia using a provocative test and barium esophagography by CC v4.0. Conclusions: CC v4.0 is more rigorous than CC v3.0 for the diagnosis of EGJOO and IEM and diagnoses achalasia more accurately by using provocative tests and FLIP. Further studies on the treatment outcomes following diagnosis with CC v4.0 are needed.

Risk factors associated with recurrence of gastric hyperplastic polyps: a single-center, long-term, retrospective cohort study.

BACKGROUND: The likelihood of recurrence of gastric hyperplastic polyps (GHPs) following endoscopic resection and the need for long-term follow-up remain unknown. We, therefore, aimed to investigate the factors associated with the recurrence and cumulative incidence of GHPs over a 10-year period. METHODS: Between May 1995 and December 2020, 1,018 GHPs > 1 cm were endoscopically resected from 869 patients. Medical records of these patients were retrospectively reviewed and their clinical features and outcomes were assessed. Groups of GHPs with recurrence and those without recurrence group were compared, and univariate and multivariable analyses were performed to identify the potential risk factors for GHP recurrence. RESULTS: A total of 104 (12.0%) patients who underwent endoscopic removal of GHPs experienced recurrence. Compared to patients without recurrent GHPs, those with recurrent GHPs showed considerably larger median polyp size (28 mm vs. 14 mm, P < 0.001), a higher proportion of multiple polyps (41.3% vs. 29.3%, P = 0.020), polyps with lobulation (63.5% vs. 40.3%, P = 0.001), and exudate (63.5% vs. 46.8%, P = 0.001). Compared to the local recurrence (n = 52) group, the metachronous recurrence (n = 52) group had larger median polyp size (20 mm vs. 16 mm, P = 0.006) as well as higher rates of polyp lobulation (86.5% vs. 40.4%, P < 0.001) and exudate (82.7% vs. 44.4%, P = 0.001). After primary GHP excision, the cumulative incidence of recurrence was 7.2%, 12.7%, and 19.6% at 2 years, 5 years, and 10 years, respectively. CONCLUSION: The incidence of GHP recurrence following endoscopic excision increased as the follow-up period increased, especially in patients whose GHPs were large-sized, multiple, or characterized by surface exudates/lobulations.

Photoactive intragastric satiety-inducing device using polymeric photosensitizers for minimally invasive weight loss treatment.

An intragastric satiety-inducing device (ISD) located in the stomach induce satiety and fullness in the absence of food by continuously pressing on the distal esophagus and cardia of the stomach. To improve the therapeutic function of ISD, Chlorin e6 (Ce6) was embedded in a disk portion of ISD, generating reactive oxygen species and stimulating endocrine cells under the laser irradiation. Since Ce6 has remarkable light efficiency but poor solubility in various solvents, it is essential to use a polymeric photosensitizer and optimize a suitable coating solution composition. Methoxy polyethylene glycol-Ce6 was uniformly coated and the spontaneous release amount of the Ce6 from the device could be reduced, which induced photo-responsive cell death and reduced ghrelin levels in vitro. In mini pigs operated single therapy (PDT or ISD) or combination therapy (Photoreactive ISD), there were differences in body weight (control: 28% vs. Photoreactive ISD: 4%, P < 0.001), ghrelin (control: 4% vs. Photoreactive ISD: 35%, P < 0.001), and leptin levels (control: 8% vs. Photoreactive PDT: 35%, P < 0.001) at 4 weeks.

Incidence, Morbidity, and Mortality of Achalasia: A Nationwide, Population-Based Cohort Study in South Korea.

Background/Aims: Although an association between achalasia and esophageal cancer has been reported, whether achalasia confers a substantial increase in mortality is unknown. Moreover, the causes of death related to achalasia have not been investigated. We performed this nationwide, population-based cohort study on achalasia because no such study has been performed since the introduction of high-resolution manometry in 2008. Methods: This study was performed using data extracted from the Korean National Health Insurance Service database, covering a 9-year period from 2009 to 2017. Control participants without a diagnostic code for achalasia were randomly selected and matched by sex and birth year at a case-to-control ratio of 1:4. Data on the cause of death from Statistics Korea were also analyzed. Results: The overall incidence of achalasia was 0.68 per 100,000 person-years, and the prevalence was 6.46 per 100,000 population. Patients with achalasia (n=3,063) had significantly higher adjusted hazard ratio (aHR) for esophageal cancer (aHR, 3.40; 95% confidence interval [CI], 1.25 to 9.22; p=0.017), pneumonia (aHR, 2.30; 95% CI, 1.89 to 2.81; p<0.001), aspiration pneumonia (aHR, 3.92; 95% CI, 2.38 to 6.48; p<0.001), and mortality (aHR, 1.68; 95% CI, 1.44 to 1.94; p<0.001). Esophageal cancer carried the highest mortality risk (aHR, 8.82; 95% CI, 2.35 to 33.16; p=0.001), while pneumonia had the highest non-cancer mortality risk (aHR, 2.28; 95% CI, 1.31 to 3.96; p=0.004). Conclusions: In this nationwide study, achalasia was associated with increased risk of mortality. Esophageal cancer and pneumonia were the most common comorbidities and the major causes of death in patients with achalasia.

Comparison of endoscopic submucosal dissection and surgery for early gastric cancer that is not indicated for endoscopic resection in elderly patients.

BACKGROUND: Endoscopic submucosal dissection (ESD) is sometimes performed for early gastric cancer (EGC) which is not indicated for endoscopic resection (ER) in elderly patients considering old age and comorbidities. We aimed to compare outcomes between ESD and surgery in elderly patients with EGC that is not indicated for ER. METHODS: Elderly patients aged ≥ 75 years who underwent either ESD or surgery for EGC which was not indicated for ER between 2005 and 2015 were retrospectively investigated. RESULTS: Among a total of 294 patients, 59 (20.1%) and 235 (79.9%) patients underwent ESD and surgery as the initial treatment, respectively. The ESD group had smaller size of tumors (25 vs. 30 mm, p = .001) and higher rate of differentiated-type cancer than the surgery group had (88.1% vs. 60.9%, p = 0.001). With a median observation period of 91.8 months (range 11.6-198.1 months), 141 (48.0%) patients died: 25 (42.4%) and 116 (49.4%) patients in the ESD group and the surgery group, respectively. Overall survival and disease-free survival between the two groups had no significant differences (p = 0.982. p = 0.155, respectively). CONCLUSIONS: ESD may be an alternative option for EGC which is not indicated for ER in elderly patients aged ≥ 75 years, considering old age and comorbidity.