Endoscopic resection for gastric submucosal tumors: A single-center experience in Japan.

Objectives: Endoscopic resection (ER) for gastric submucosal tumors (SMTs) has gained prominence in recent years, with studies emerging from various countries. However, there is a paucity of reports from Japan. We aimed to elucidate the efficacy and safety of ER for gastric SMT in Japan. Methods: In this retrospective observational study, we investigated the outcomes of consecutive patients who underwent ER for gastric SMT from January 2017 to May 2023. The outcome variables assessed included the complete resection rate, procedure time, closure-related outcomes, and the incidence of adverse events. Results: A total of 13 patients were included in the analysis. The median procedure time was 163 (55-283) min. Complete full-thickness resection was performed in seven cases, while in four cases, the serosa remained, and in two cases, the outer layer of the muscularis propria remained. In two cases where the SMT was located on the anterior side, conversion to laparoscopic surgery became necessary, resulting in a procedural success rate of 84.6% (11/13). Excluding these two cases, endoscopic closure of the defect was successfully accomplished in the remaining 11 cases. R0 resection was achieved in 12 out of 13 cases (92.3%). Although one patient had peritonitis, which was successfully treated conservatively, no other treatment-related adverse events were encountered. Conclusions: Although ER for SMT on the anterior side may be challenging, our experience revealed that ER is a safe and efficacious approach for gastric SMT.

Propofol-alone sedative efficacy in observational biliopancreatic endoscopic ultrasound.

Objectives: Appropriate sedative and analgesic selection is essential to reduce patient discomfort and body movement to safely conduct endoscopic ultrasonography (EUS). However, few cases have examined sedation with propofol in EUS, and few studies the need for combined analgesia. In this study, we retrospectively evaluated the usefulness and safety of propofol without analgesics for sedation in biliopancreatic observational EUS. Methods: This single-center retrospective study included 516 observational biliopancreatic EUS procedures using propofol alone performed between April 2021 and March 2023. The primary and secondary endpoints were the observational biliopancreatic EUS results obtained with propofol alone and adverse event occurrence, respectively. Results: The median examination time and total propofol dose were 22 (range: 10-67) min and 186.5 (range: 50-501) mg, respectively. The median starting Richmond Agitation-Sedation Scale and Visual Analog Scale scores were -5 (range: -5-1) and 0 (range: 0-10), respectively. The median recovery time was 22 (range: 5-80) min. Adverse events occurred in 60 (11.6%) patients. Trainee-performed examination (odds ratio [OR] 3.52, 95% confidence interval [CI]: 1.63-7.60, p = 0.0014) and examination length (>22 min; OR 1.67, 95% CI: 0.95-2.92, p = 0.07) were risk factors for adverse events.High body mass index (OR 1.87, 95% CI: 1.10-3.16, p = 0.02) and extended examination time (OR 4.23, 95% CI: 2.08-8. 57, p < 0.001) were risk factors for delayed recovery. Conclusions: During observational biliopancreatic EUS, propofol is useful as a single sedative and offers high patient satisfaction and relative safety.

Clinical utility of a novel anchor pronged clip for mucosal defect closure after colorectal endoscopic submucosal dissection (with video).

Background and study aims The MANTIS Clip (Boston Scientific) is a novel anchor pronged clip designed to enhance tissue grasping and facilitate the closure of defects in the gastrointestinal tract. This study evaluates the feasibility and effectiveness of the MANTIS Clip for closing mucosal defects following colorectal endoscopic submucosal dissection (C-ESD). Patients and methods A retrospective single-center study was conducted on patients who underwent C-ESD with MANTIS Clip closure from May 2023 to April 2024. The primary outcome measured was the complete closure success rate. Secondary outcomes included defect size, sustained closure rate, closure time, number of clips used, adverse events (AEs), and hospital stay duration. Results The MANTIS Clip was used in 52 cases. The complete closure rate was 98.1% (51/52), with a sustained closure rate of 96.1% (49/51). The median closed defect size was 32 mm, with the largest being 62 mm. The median closure time was 8 minutes. Typically, one MANTIS Clip per defect was used, with only one lesion requiring two clips. The median number of additional clips used was seven. AEs included one case of bleeding (1.9%) and one case of post-ESD coagulation syndrome (1.9%), both managed without extending hospital stays. The median C-reactive protein level on the first day post-ESD was 0.35 mg/dL and the median hospital stay was 5 days. Conclusions The MANTIS Clip is effective and practical for mucosal defect closure post-C-ESD, demonstrating high success and sustained closure rates with minimal complications. Future multicenter randomized trials are needed to further assess its efficacy and safety.

Peroral endoscopic myotomy as a treatment for Killian-Jamieson diverticulum (KJ-POEM).

Background and study aims Killian-Jamieson diverticulum (KJD) is a rare type of esophageal diverticulum that occurs in a specific area called the Killian-Jamieson space. Although surgery has been the conventional treatment for symptomatic KJD, minimally invasive endoscopic techniques, particularly Killian-Jamieson per-oral endoscopic myotomy (KJ-POEM), have emerged as an alternative. The aim of the study was to evaluate the effectiveness and safety of KJ-POEM in treating KJD. Patients and methods This was an international, multicenter, retrospective study that included patients who underwent KJ-POEM for symptomatic KJD from October 16, 2018 to April 12,2023. The primary outcome was clinical success, defined as complete or near-complete resolution of symptoms (i.e., post-procedure Kothari-Haber Score ≤ 2).  Secondary outcomes were technical success (defined as successful completion of all procedural steps), rate and severity of adverse events (AEs), total procedure duration, and symptom recurrence during follow-up. Results A total of 13 patients (mean age 65.23 years, 6 female) with KJD and a mean pre-procedure Kothari-Haber Score of 6 (standard deviation [SD] 2.16) underwent KJ-POEM across 10 participating centers. Clinical success and technical success were achieved in all cases (100%) with a mean post-procedure Kothari-Haber Score of 0.91 (SD 0.99). There were no AEs and no cases of injury to the recurrent laryngeal nerve. Mean length of hospital stay was 1.09 days (SD 0.74). Mean follow-up time was 9.41 months (SD 10.07) post-procedure. There was no post-procedure symptom recurrence any patient. Conclusions KJ-POEM is a safe and effective alternative treatment for symptomatic KJD with excellent short/mid-term outcomes.

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.

Loop9 closure technique for mucosal defects after colorectal endoscopic submucosal dissection (with video).

Background and study aims Mucosal defect closure after colorectal endoscopic submucosal dissection (ESD) has the potential to reduce the occurrence of delayed adverse events (AEs) such as bleeding and perforation. This study aimed to assess the feasibility and effectiveness of the Loop9 method for closing mucosal defects following colorectal ESD. Patients and methods A retrospective single-center study was conducted using prospectively collected data from May 2020 to March 2023. Loop9 was deployed through a single instrument channel and anchored with clips at the defect site. Closure was accomplished by tightening the loop and deploying additional conventional clips as needed for complete closure. The primary outcome was complete closure rate, with secondary outcomes including the sustained closure rate at 4 to 5 days post-ESD, closed defect size, closure time, number of additional clips, and incidence of delayed AEs. Results This study included 118 cases. Complete closure was achieved in 96.6% of cases (114/118) with a sustained closure rate of 93.9% (107/114). The median size of the closed mucosal defects was 30 mm (interquartile range [IQR]: 25-38, range: 15-74). The median closure time was 14 minutes (IQR: 11.25-17), and the median number of additional clips deployed was six (IQR: 4-7). Stenosis requiring balloon dilatation was observed in one patient; however, there were no instances of post-ESD bleeding or delayed perforation. Conclusions The Loop9 method proved feasible and effective for closing mucosal defects following colorectal ESD, achieving high rates of complete and sustained closure.

Impact of peroral endoscopic myotomy on the endoscopic pressure study integrated system.

OBJECTIVES: The endoscopic pressure study integrated system (EPSIS) is an endoscopic diagnostic system utilized for evaluation of lower esophageal sphincter function. Although previous studies have determined that EPSIS was effective as a tool for the diagnosis of achalasia, it remains uncertain if EPSIS can detect significant changes before and after peroral endoscopic myotomy (POEM), which is the premier treatment for achalasia. This study aimed to evaluate the effectiveness of EPSIS as an objective diagnostic tool for assessing the clinical effect of POEM. METHODS: We conducted a retrospective analysis of patients who underwent POEM from January 2022 to December 2023. The patients underwent EPSIS preoperatively and 2 months postoperatively. Intragastric pressure (IGP) parameters, including the maximum IGP, IGP difference, and waveform gradient were compared pre- and post-POEM. These parameters also were compared between two groups: the postoperative gastroesophageal reflux disease (GERD) group and the non-GERD group. RESULTS: A total of 50 patients were analyzed. The mean maximum IGP was significantly lower postoperatively than preoperatively (15.0 mmHg vs. 19.8 mmHg, P < 0.001). The mean IGP difference and waveform gradient were also significantly lower postoperatively than preoperatively (8.0 mmHg vs. 12.2 mmHg, P < 0.001; and 0.26 mmHg/s vs. 0.43 mmHg/s, P < 0.001, respectively). The mean postoperative waveform gradient was significantly lower in the GERD group (17 patients, 34%) than in the non-GERD group (33 patients, 66%) (0.207 mmHg vs. 0.291 mmHg, P = 0.034). CONCLUSION: The results supported the use of EPSIS as an effective diagnostic tool for assessing the effect of POEM.

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Video 1XXX.

Closure in antireflux mucoplasty using anchor prong clips: dead space-eliminating technique.

Video 1Introducing the dead space eliminating technique (DET), a closure method using anchor pronged clips for antireflux mucoplasty in treating proton pump inhibitor refractory-dependent GERD. DET ensures comprehensive dead space elimination during closure.

Unified Magnifying Endoscopic Classification (UMEC) of Gastrointestinal Lesions: A North American Validation Study.

Background and study aim: Magnifying endoscopy enables the diagnosis of advanced neoplasia throughout the gastrointestinal tract. The unified magnifying endoscopic classification (UMEC) framework unifies optical diagnosis criteria in the esophagus, stomach, and colon, dividing lesions into three categories: non-neoplastic, intramucosal neoplasia, and deep submucosal invasive cancer. This study aims to ascertain the performance of North American endoscopists when using the UMEC. Methods: In this retrospective cohort study, five North American endoscopists without prior training in magnifying endoscopy independently diagnosed images of gastrointestinal tract lesions using UMEC. All endoscopists were blinded to endoscopic findings and histopathological diagnosis. Using histopathology as the gold standard, the endoscopists' diagnostic performances using UMEC were evaluated. Results: A total of 299 lesions (77 esophagus, 92 stomach, and 130 colon) were assessed. For esophageal squamous cell carcinoma, the sensitivity, specificity, and accuracy ranged from 65.2% (95%CI: 50.9-77.9) to 87.0% (95%CI: 75.3-94.6), 77.4% (95%CI: 60.9-89.6) to 96.8% (95%CI: 86.8-99.8), and 75.3% to 87.0%, respectively. For gastric adenocarcinoma, the sensitivity, specificity, and accuracy ranged from 94.9% (95%CI: 85.0-99.1) to 100%, 52.9% (95%CI: 39.4-66.2) to 92.2% (95%CI: 82.7-97.5), and 73.3% to 93.3%. For colorectal adenocarcinoma, the sensitivity, specificity, and accuracy ranged from 76.2% (95%CI: 62.0-87.3) to 83.3% (95%CI: 70.3-92.5), 89.7% (95%CI: 82.1-94.9) to 97.7% (95%CI: 93.1-99.6), and 86.8% to 90.7%. Intraclass correlation coefficients indicated good to excellent reliability. Conclusion: UMEC is a simple classification that may be used to introduce endoscopists to magnifying narrow-band imaging and optical diagnosis, yielding satisfactory diagnostic accuracy.

Enhancing closure efficacy in antireflux mucoplasty through endoscopic hand-suturing technique.

Video 1XXX.

Advancements in minimally invasive endoscopic treatment: Navigating deeper layers for upper gastrointestinal lesion.

The field of minimally invasive endoscopic treatment has seen a continual progression, marked by significant advancements in treatment devices and the refinement of endoscopic techniques. While endoscopic resection has become the standard for treating superficial gastrointestinal neoplasms, a proactive approach becomes imperative when dealing with lesions that extend beyond the submucosal layer and deeper into the muscularis propria. The ongoing evolution of endoscopic closure techniques has facilitated the introduction of advanced procedures such as endoscopic muscularis dissection, endoscopic subserosal dissection, and endoscopic full-thickness resection. This evolution is achieved by the commitment to improve the efficacy and precision in treating challenging lesions. Nevertheless, there is currently a lack of definitive guidelines or consensus regarding the specifics of deeper layer dissection. Drawing from prior research and clinical insights, this review discusses indications, techniques, clinical outcomes, and future perspectives of deeper layer dissection.

Docking Proteins Upregulate IL-1ß Expression in Lower Esophageal Sphincter Muscle in Esophageal Achalasia.

Background/Objectives: Esophageal achalasia is an archetypal esophageal motility disorder characterized by abnormal peristalsis of the esophageal body and impaired lower esophageal sphincter (LES) relaxation. Methods: In this study, the mRNA expression of docking proteins 1 and 2 (DOK1 and DOK2, respectively) were analyzed and the mechanisms underlying achalasia onset were investigated. Results:DOK1 and DOK2 mRNA levels significantly increased in the LES of patients with achalasia. Moreover, significant correlations were observed between IL-1ß and DOK1, IL-1ß and DOK2, ATG16L1 and DOK1, and HSV1-miR-H1-3p and DOK2 expression levels. However, a correlation between ATG16L1 and DOK2 or between HSV-miR-H1-3p and DOK1 expression was not observed. In addition, a positive correlation was observed between patient age and DOK1 expression. Microarray analysis revealed a significant decrease in the expression of hsa-miR-377-3p and miR-376a-3p in the LES muscle of patients with achalasia. Conclusions: These miRNAs possessed sequences targeting DOK. The upregulation of DOK1 and DOK2 expression induces IL-1ß expression in the LES of achalasia patients, which may contribute to the development of esophageal motility disorder.

Clinical outcomes of peroral endoscopic myotomy with and without septotomy for management of epiphrenic diverticula: an international multicenter experience.

BACKGROUND AND AIMS: There are few data favoring the need for septotomy at the time of peroral endoscopic myotomy (POEM) or if POEM alone is sufficient. Our aim was to compare POEM outcomes with and without septotomy (POEM+S or POEM-S) in patients with symptomatic epiphrenic diverticula (ED) and an underlying motility disorder. METHODS: This was an international, multicenter retrospective study involving 21 centers between January 2014 and January 2023. Patients with ED and an underlying motility disorder who underwent POEM were included. The primary outcome was clinical success (Eckardt score [ES] ≤3 or a 1-point drop in ES for patients with baseline ES <3) without the need for repeat surgical/endoscopic interventions during follow-up. RESULTS: A total of 85 patients (mean age, 64.29 ± 17.1 years; 32 [37.6%] female) with ED and underlying motility disorder underwent POEM+S (n = 47) or POEM-S (n = 38). Patients in the POEM+S group had a significantly higher mean pre-POEM ES (7.3 ± 2.1 vs 5.8 ± 2; P = .002). The most common indication for POEM was achalasia (51% in the POEM+S cohort and 51.8% in the POEM-S cohort; P = .7). A posterior approach was favored in the POEM+S group (76.6% vs 52.6%; P = .02). A similar rate of technical success was seen in both groups (97.9% vs 100%; P = .1). The rate of adverse events was similar between the 2 cohorts (4.2% vs 8.1%; P = .6). The median length of hospital stay after POEM-S was significantly longer compared with POEM+S (2 days [interquartile range (IQR), 1-4 days] vs 1 day [IQR, 1-2 days]; P = .005). Clinical success was equivalent between the 2 groups (83% vs 86.8%; P = .6) at a median follow-up duration of 8 months (IQR, 3-19 months). CONCLUSIONS: In patients with ED and an underlying motility disorder, both POEM+S and POEM-S are equally safe and effective, with similar procedure duration and a low recurrence rate at short-term follow-up. Future comparative prospective studies with long-term follow-up are required to validate these findings.

Novel scale for evaluating the therapeutic efficacy of per-oral endoscopic myotomy in achalasia.

BACKGROUND: Symptom scales for achalasia after per-oral endoscopic myotomy (POEM) are lacking. This study aimed to propose a new scale based on the conventional Eckardt score (c-ES) and evaluate persistent symptoms that impair patients' quality of life (QOL) post-POEM. METHODS: Dysphagia, regurgitation, and chest pain frequencies were assessed using a 6-point scale modified-ES (m-ES) after POEM, with "occasional" symptoms on the c-ES further subdivided into three-period categories on m-ES. Symptom severity was further evaluated using a 5-point scale ranging from 1 to 5 points, with a score ≥ 3 points defined as persistent symptoms impairing QOL. We analyzed the correlation between the m-ES and severity score, diagnostic performance of the m-ES for persistent symptoms, and overlaps between each residual symptom. RESULTS: Overall, 536 patients (median follow-up period, 2.9 years) post-POEM were included in this multicenter study. Significant correlations were observed between the m-ES and severity scores for dysphagia (r = 0.67, p < 0.01), regurgitation (r = 0.73, p < 0.01), and chest pain (r = 0.85, p < 0.01). Twenty-six patients (4.9%) had persistent symptoms post-POEM, and 23 of them had m-ES-specific symptom frequency ≥ once a month, which was determined as the optimal frequency threshold for screening persistent symptoms. The total m-ES predicted persistent symptoms more accurately than the total c-ES (area under the curve: 0.95 vs. 0.79, p < 0.01). Furthermore, dysphagia and chest pain were the major residual symptoms post-POEM covering 91.4% of regurgitation. CONCLUSIONS: The new post-POEM scale successfully evaluated the QOL-based patient symptom severities. Our study implied the possibility of a simpler scale using residual dysphagia and chest pain.

Endoscopic pressure study integrated system using an ultrathin gastroscope for the functional assessment of the lower esophageal sphincter.

OBJECTIVES: The endoscopic pressure study integrated system (EPSIS) represents an innovative approach for evaluating lower esophageal sphincter function by monitoring intragastric pressure using diagnostic gastroscopes. This study aimed to assess the feasibility and validity of employing ultrathin gastroscopes for EPSIS. METHODS: A retrospective analysis was conducted on a database of consecutive patients who underwent EPSIS using both ultrathin and regular gastroscopes between September 2021 and October 2023. The study compared EPSIS parameters between the two gastroscope types to evaluate the correlation of key metrics. RESULTS: Thirty patients underwent EPSIS with both ultrathin and regular gastroscopes. Significant positive correlations were observed in the pressure waveform: maximum intragastric pressure (mmHg) (ρ = 0.82, P < 0.001) and intragastric pressure gradient (mmHg/s) (ρ = 0.80, P < 0.001) when comparing the two gastroscopes. Maximum intragastric pressure (15.5 [5.3-20.3] vs. 18.5 [3.4-21.6], P < 0.001) and pressure gradient (0.16 [0.013-0.41] vs. 0.24 [0.0039-1.13], P < 0.001), (median [range]) were significantly lower with ultrathin gastroscopes. CONCLUSIONS: This study establishes that EPSIS parameters obtained with an ultrathin gastroscope exhibit a significant correlation with those obtained using a regular gastroscope, with each EPSIS parameter consistently lower. These findings support the viability of EPSIS for ultrathin gastroscopy and highlight its potential as a diagnostic tool for assessing lower esophageal sphincter function.

The interplay between alterations in esophageal microbiota associated with Th17 immune response and impaired LC20 phosphorylation in achalasia.

BACKGROUND: Achalasia is an esophageal motility disorder with an unknown etiology. We aimed to determine the pathogenesis of achalasia by studying alterations in esophageal smooth muscle contraction and the associated inflammatory response, and evaluate the role of esophageal microbiota in achalasia development. METHODS: We analyzed esophageal mucosa and lower esophageal sphincter (LES) samples, obtained from patients with type II achalasia who underwent peroral endoscopic myotomy. Esophageal conditioned media obtained from patients were transferred into the mouse esophagus to determine whether the esophageal intraluminal environment is associated with achalasia. RESULTS: Approximately 30% of 20-kDa myosin light chains (LC20) was phosphorylated in LES from the control group under resting and stimulated conditions, whereas less than 10% of LC20 phosphorylation was detected in achalasia under all conditions. The hypophosphorylation of LC20 in achalasia was associated with the downregulation of the myosin phosphatase-inhibitor protein CPI-17. Th17-related cytokines, including IL-17A, IL-17F, IL-22, and IL-23A, were significantly upregulated in achalasia. α-Diversity index of esophageal microbiota and the proportion of several microbes, including Actinomyces and Dialister, increased in achalasia. Actinomyces levels positively correlated with IL-23A levels, whereas Dialister levels were positively associated with IL-17A, IL-17F, and IL-22 levels. Esophageal IL-17F levels increased in mice after oral administration of the conditioned media. CONCLUSIONS: In LES of patients with achalasia, hypophosphorylation of LC20, a possible cause of impaired contractility, was associated with CPI-17 downregulation and an increased Th17-related immune response. The esophageal intraluminal environment, represented by the esophageal microbiota, could be associated with the development and exacerbation of achalasia.