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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. [ABSTRACT FROM AUTHOR]

Aim: We conducted a multicenter study on classical laparoscopic and endoscopic cooperative surgery (LECS) and LECS‐related procedures to retrospectively clarify the safety, problems, and mid‐term outcomes of these methods after their coverage by the national health insurance. Methods: A total of 201 patients who underwent classical LECS/LECS‐related procedures for gastric submucosal tumors (G‐SMTs) in 21 institutions affiliated with the Laparoscopy Endoscopy Cooperative Surgery Study Group from April 2014 to March 2016 were included. Data was retrospectively obtained from the patients' charts. Results: The most common surgical procedure was classical LECS (155 patients, 77.1%), non‐exposed endoscopic wall inversion surgery (22 patients, 11.4%), a combination of laparoscopic and endoscopic approaches to neoplasia with non‐exposure technique (16 patients, 8%), and closed LECS (two patients, 1%). Only six (3%) patients underwent LECS with gastrostomy. The mean operative time and blood loss were 188.4 (70–462) minutes and 23.3 (0–793) g, respectively. Ten (5%) patients developed postoperative complications (Clavien–Dindo classification grade II or higher). Two patients needed reoperation due to postoperative bleeding or anastomotic leakage. All tumors were resected with negative margins. A total of 127 (63.2%) patients underwent follow‐up observations for over 36 months, one of whom had a recurrence of peritoneal dissemination and one had poor oral intake. Conclusion: Classical LECS and LECS‐related procedures for G‐SMTs have favorable short/mid‐term outcomes. We conducted a multicenter study on classical laparoscopic and endoscopic cooperative surgery (LECS) and LECS‐related procedures to retrospectively clarify the safety, problems, and mid‐term outcomes of these methods after their coverage by the national health insurance. A total of 201 patients who underwent classical LECS/LECS‐related procedures for gastric submucosal tumors (G‐SMTs) in 21 institutions affiliated with the Laparoscopy Endoscopy Cooperative Surgery Study Group from April 2014 to March 2016 were included. Classical LECS and LECS‐related procedures for G‐SMTs have favorable short/mid‐term outcomes. [ABSTRACT FROM AUTHOR]

Background and Aims: Killian‐Jamieson diverticulum (KJD) is a relatively uncommon variant of pharyngoesophageal diverticula, distinct from the more prevalent Zenker diverticulum. However, literature on endoscopic management of KJD remains limited. This study aimed to elucidate the efficacy and safety of peroral endoscopic septotomy (POES) as a treatment approach for symptomatic KJD. Methods: In this retrospective observational study, we investigated the outcomes of nine consecutive patients who underwent POES for KJD between January 2019 and May 2023. Follow‐up data of at least 2 months post‐treatment were analyzed. The primary outcome measure was the technical success rate of POES. Secondary outcomes encompassed the clinical success rate, defined as symptomatic improvement 2 months after POES, and the incidence of adverse events. Results: All patients presented with dysphagia, with a median symptom duration of 6 months (interquartile range [IQR]: 3–12 months). The median diverticulum size was 32 mm (IQR: 24–42 mm). The median duration of the operation time was 66 min (IQR: 60–109). A 100% technical success rate was achieved, with complete closure of the defect in all cases. There were no adverse events related to this treatment. The median hospitalization duration was 5 days (IQR: 4–6), and the clinical success rate was 88.9%. Follow‐up barium esophagograms exhibited significant improvement in the flow of the barium for all patients. Conclusions: Despite the relatively limited case volume, our findings underscore that POES is a safe and efficacious approach for managing symptomatic KJD. [ABSTRACT FROM AUTHOR]

Objectives: Anti‐reflux mucosectomy (ARMS) and anti‐reflux mucosal ablation (ARMA) were developed as interventions for proton pump inhibitor (PPI)‐refractory/‐dependent gastroesophageal reflux disease (GERD). Although ARMS and ARMA are established treatments for PPI‐refractory GERD, reliance on natural healing for ulcer scar formation introduces uncertainty and bleeding risk. To address these issues, we introduced a novel approach called anti‐reflux mucoplasty (ARM‐P), which involves immediate closure of mucosal defects following mucosectomy. This pilot study aims to evaluate the safety, feasibility, and efficacy of ARM‐P. Methods: A retrospective single‐center study was conducted using prospectively collected data from October 2022 to July 2023. Patients with PPI‐refractory/‐dependent GERD who underwent ARM‐P were included. The study evaluated technical success of ARM‐P, before and after ARM‐P GERD‐Health Related Quality of Life Questionnaire, GerdQ, and Frequency Scale for the Symptoms of GERD scores, along with PPI discontinuation and endoscopic esophagogastric junction morphology. Results: A total of 20 patients with a median age of 61.5 years underwent the ARM‐P procedure. The procedure achieved 100% technical success without adverse events. After ARM‐P, 55.0% discontinued PPI usage and 15.0% reduced PPI dose by half. Median GERD‐Health Related Quality of Life Questionnaire score improved from 21 to 6 (P = 0.0026), median GerdQ score improved from 9 to 7 (P = 0.0022), and median Frequency Scale for the Symptoms of GERD score decreased from 16 to 7 (P = 0.0003). Median Hill's Classification significantly improved from grade III to grade I (P = 0.0001). Conclusions: This study presents the first pilot report of ARM‐P, demonstrating its procedural safety, technical feasibility, and short‐term efficacy. [ABSTRACT FROM AUTHOR]

Objectives: The endoscopic pressure study integrated system (EPSIS) is a novel diagnostic tool used to evaluate lower esophageal sphincter (LES) function. EPSIS allows the measurement of intragastric pressure (IGP) during gastric insufflation through esophagogastroduodenoscopy (EGD) and records its pressure waveform. This study aimed to assess the usefulness and applicability of EPSIS as an adjunct diagnostic modality for achalasia. Methods: This case–control study was conducted using a database of patients who underwent EGD, barium swallow (BS), high‐resolution manometry (HRM), and EPSIS between January 2022 and December 2022. The achalasia (experimental) group (n = 35) consisted of patients with a definitive diagnosis of achalasia. The control group (n = 34) consisted of patients with no abnormalities in EGD, BS, or HRM and no abnormal acid reflux confirmed with 24‐h pH‐impedance monitoring. EPSIS findings were compared between the two groups and characterized by the waveform pattern (uphill or flat), maximum IGP (IGP‐Max), pressure difference, and the gradient of the waveform. Results: All patients in the achalasia group showed an uphill pattern, in contrast to 21 patients (61.8%) in the control group. IGP‐Max demonstrated the best diagnostic accuracy for achalasia, with a cut‐off value of 15.8 mmHg (100% sensitivity, 58.8% specificity, and area under the curve [AUC] 0.78). The pressure gradient also demonstrated good diagnostic accuracy, with a cut‐off value of 0.40 mmHg/s (80% sensitivity, 61.8% specificity, and AUC 0.76). Conclusion: This study demonstrated that EPSIS can be applied as a diagnostic modality in patients with achalasia. [ABSTRACT FROM AUTHOR]

Objectives: Minimally invasive treatments have been applied for gastroesophageal reflux disease (GERD), but the long‐term results are controversial. Antireflux mucosectomy (ARMS) is a simple endoscopic procedure that does not require the insertion of a foreign body. We provide the first report on the long‐term results of ARMS. Methods: This was a single‐center, single‐arm trial, prospective study of 88 patients with proton pump inhibitor (PPI)‐refractory GERD who underwent ARMS between June 2012 and June 2017. Primary outcomes were the rates of long‐term effectiveness and PPI discontinuation. Secondary outcomes were to compare patients' preoperative background characteristics, questionnaire, and multichannel intraluminal impedance and pH monitoring data to examine the predictive factors of ARMS. The clinical course was reviewed, including the need for additional treatment after ARMS. Results: Antireflux mucosectomy produced a long‐term effect in 68.3% of the patients, and PPI could be discontinued in 42% of patients. There were significant differences in age, intensity of preoperative symptoms, and acid‐related indicators. Forty‐five percent (27/60) had reflux hypersensitivity and ARMS provided long‐term effectiveness in 81% of these patients. There was no significant difference in subjective symptom assessment between those with short‐term and long‐term efficacy. Additional treatment was administered in 23% (14/60) and scheduled at 1–2 years' follow‐up. Conclusions: Antireflux mucosectomy showed long‐term efficacy, and many of the cases with short‐term effects were able to maintain them. In addition, ARMS is also effective in patients with reflux hypersensitivity, and provides a treatment option that bridges the gap between surgical and medical treatment. [ABSTRACT FROM AUTHOR]

Background and Aim: Anti‐reflux mucosal ablation (ARMA) is an emerging endoscopic treatment aimed at enhancing the gastroesophageal junction flap valve. This study aimed to evaluate its feasibility, effectiveness, and safety. Methods: Between May 2018 and December 2022, patients with gastroesophageal reflux disease (GERD) symptoms refractory to acid suppression medications or those dependent on such medications were enrolled for ARMA. This retrospective analysis utilized prospectively collected data from an international bi‐center study. GERD questionnaire, upper endoscopy, and 24‐h pH monitoring were conducted at 2–6 months and 12 months post‐ARMA. Clinical success was defined as a > 50% reduction in a validated GERD questionnaire. Results: A total of 68 patients underwent ARMA. Definitive GERD was diagnosed in 44 (64.7%) patients, while 24 (35.3%) exhibited reflux hypersensitivity. Clinical success rates at 2–6 months and 1 year post‐ARMA were 60% (39/65) and 70% (21/30), respectively. The median GERD‐health‐related quality of life score significantly improved from 26 to 11 at 2–6 months (P < 0.001). Among the 51 patients (71.8%) who underwent 24‐h pH monitoring, the median acid exposure time decreased from 5.3% to 0.7% (P = 0.003), accompanied by a significant reduction in esophagitis rates (P < 0.001). Multivariate analysis did not identify predictors of short‐term success. Nine (13.2%) patients experienced transient stenosis requiring balloon dilation. Conclusions: ARMA demonstrates both technical feasibility and reproducibility as a safe procedure that effectively ameliorates GERD symptoms in approximately two‐thirds of patients during short‐term follow up. Both reflux hypersensitivity and confirmed GERD patients, regardless of their response to acid suppression medication, may be suitable candidates. [ABSTRACT FROM AUTHOR]

Objectives: Reports on learning curve for peroral endoscopic myotomy (POEM) in therapeutic endoscopy nonexperts are limited. We aimed to assess the number of cases required to achieve POEM proficiency for endoscopic submucosal dissection (ESD) experts and nonexperts. Methods: This is a retrospective study at the largest POEM referral center in Japan. POEM between April 2014 and December 2020 were included. Nonexperts and ESD experts were divided by training phases: A, 1–20; B, 21–40; C, 41–60; D, 61–80; and E, 81–100 cases. Primary outcome was operation time, and the phase to reach target time (83 min) was investigated. Secondary outcomes were clinical success rate, adverse events, and post‐POEM gastroesophageal reflux disease (GERD). Results: Five hundred and sixty‐six cases were performed by 14 nonexperts, and 555 cases by 15 ESD experts. As the primary outcome, operation time in nonexperts was: A, 95 (79–115.8); B, 86.5 (71–105); C, 80 (70–100); D, 73 (64.5–100.5); and E, 73.5 (57.8–88.8) min, while in ESD experts: A, 90 (74–128); B, 77 (70–92); and C, 77 (70–93.5) min (median [interquartile range]). Operation time decreased significantly as experience increased in both groups (P < 0.001), and nonexperts required 41–60 cases to achieve proficiency, while experts required 21–40 cases. As secondary outcomes, in nonexperts, clinical success was 96.9–100%, adverse events were 5.0–9.2%, symptomatic GERD was 11.8–26.5%, and proton pump inhibitor (PPI) intake was 11.5–18.7% in each phase. While in experts, clinical success was 96.2–100%, adverse events were 3.0–5.8%, symptomatic GERD was 14.6–22.0%, and PPI intake was 12.6–17.9%. There were no significant differences among training phases. Conclusions: Non‐ESD experts require more cases to achieve proficiency in POEM. These results are useful for establishing POEM training programs and institutional implementation of the procedure. [ABSTRACT FROM AUTHOR]

Objectives: Patients with esophageal motility disorders (EMDs) including achalasia after gastric surgery have not been thoroughly characterized. Furthermore, the efficacy of peroral endoscopic myotomy (POEM) in this population should be clarified. Methods: In this retrospective multicenter study of 3707 patients with EMDs, 31 patients (0.8%) had a history of gastric surgery. Patient characteristics and POEM efficacy were compared between patients with and without previous gastric surgery. Results: In patients with EMD after gastric surgery, age at EMD diagnosis was higher (72.0 years), male sex was predominant (90.3%), and the American Society of Anesthesiologists physical status score was higher (≥II, 48.4%). High‐resolution manometry (HRM) findings did not reveal significant differences. In patients who underwent gastric surgery, atrophic gastritis was common (80.6%), and gastric cancer was the primary surgical indication (32.3%). Distal gastrectomy was performed in 28 patients (90.3%). POEM was effective (3.3% adverse events; 100% treatment success). The incidence rates of reflux esophagitis (RE) and symptomatic gastroesophageal reflux disease (GERD) were 60.0% and 16.7%, respectively, without significant intergroup differences, and severe RE was not observed in the long‐term follow‐up. Extended gastric myotomy was a risk factor for RE. Conclusion: Patients with gastric surgery often present severe disease manifestations; the surgical indication is mainly gastric cancer. HRM findings can be similarly used for diagnosis in patients with and without gastric surgery. POEM maintains safety and efficacy with acceptable RE and symptomatic GERD rates. To prevent RE, extended myotomy should be avoided. [ABSTRACT FROM AUTHOR]

Endoscopic balloon dilatation is an established treatment for benign gastrointestinal strictures. In order to dilatate safely, it is necessary to dilatate gradually and preferably under direct endoscopic visualization. However, it is currently difficult to achieve dilatation widths of 20–30 mm with commercial products and of over 30‐mm with endoscopic visualization. Therefore, a safe and innovative application technique is needed for patients who need these 20‐mm or greater dilatation widths. We have developed two methods that enable more than 20‐mm dilatation under direct visualization. (i) Single‐barrel method: an endoscopic balloon dilatation catheter was fixed with grasping forceps at the tip of the endoscope and carried into the stomach. The balloon catheter was released from the endoscope to create a retroflexed view. The endoscope and balloon were positioned adjacent to each other at the gastric cardia. The balloon was inflated gradually and the esophagogastric junction was dilatated under direct visualization. (ii) Double‐barrel method: the same procedure was repeated with two balloons. Theoretically, we achieved a dilatation of >30‐mm in diameter. These modified methods may be helpful for esophagogastric junction strictures, such as esophageal achalasia (serving as an initial endoscopic balloon dilatation prior to using a 30‐mm achalasia balloon), or for functional strictures after Nissen fundoplication. In conclusion, our simple, modified method enables safe and gradual dilatation under direct endoscopic visualization. Additionally, combination of the sizes of one or two balloons can achieve various widths of dilatation. [ABSTRACT FROM AUTHOR]

Background and Aim: The perioperative management and clinical course of per‐oral endoscopic myotomy for patients receiving antithrombotic therapy remains unknown. This study aimed to clarify the status of antithrombotic therapy in per‐oral endoscopic myotomy and to determine its safety and efficacy. Methods: Patients treated with per‐oral endoscopic myotomy from 2010 to 2019 in seven high‐volume centers in Japan were retrospectively investigated. The patients' characteristics and antithrombotic agent management were analyzed; clinical outcomes were compared with those without antithrombotic agents. Results: Of 2752 patients who underwent per‐oral endoscopic myotomy, 120 patients on antithrombotic therapy (mean age 71.0 years, American Society of Anesthesiologists class II–IV [67.5%]) were identified. Antiplatelet, anticoagulant, and a combination of antithrombotic agents were used in 82, 30, and 8 patients, respectively. The perioperative management adhered to the therapeutic endoscopy guidelines published by the Japanese Society of Gastroenterological Endoscopy in most patients (88.3%). A poorer clinical baseline status (American Society of Anesthesiologists class II–IV; 67.0% vs 24.3%) and the sigmoid type (40.7% vs 22.3%) were more frequently observed in patients with achalasia on antithrombotic therapy. However, the clinical success (Eckardt score ≤ 3; 97.6% vs 94.6) and adverse event rates, such as bleeding and thromboembolic events (5.5% vs 4.7%), did not show inferiority. Conclusions: Per‐oral endoscopic myotomy on antithrombotic therapy is safe and effective. However, caution is required as patients on antithrombotic therapy tend to have poorer baseline health and achalasia statuses. Our experience should help establish perioperative management with antithrombotic therapy. [ABSTRACT FROM AUTHOR]

Objectives: Endocytoscopy (EC) is an ultra‐high magnification endoscopy designed to provide in vivo histologic assessment. This study aimed to evaluate the diagnostic yield of the newly developed fourth‐generation EC for esophageal squamous lesions by using a modified EC classification. Methods: A total of 2548 EC images of 57 esophageal targeted areas between June 2015 and October 2017 were retrospectively collected. Two lesions with low‐quality images were excluded. Only EC images were independently reviewed by two expert and two non‐expert endoscopists. The lesions were classified according to a three‐tier modified EC classification. We used a multilevel logistic regression to analyze the data. Results: The sensitivity and specificity of diagnosing non‐squamous cell cancer (SCC) vs SCC were 82.5% and 83.0% by the experts; 90.1% and 75.0% by non‐experts. The interobserver agreement among the four raters was good (kappa statistic 0.59). The diagnostic accuracy of experts and non‐experts was similar (P = 0.16 for specificity and P = 0.20 for sensitivity). The sensitivity and specificity of EC for non‐neoplasia vs neoplasia were 88.7% and 74.6% by experts; 90.3 and 52.1% by non‐experts. The interobserver agreement among the four raters was moderate (kappa statistic 0.44). The specificity of experts was higher compared to non‐experts, although the difference did not reach statistical significance (P = 0.08 for specificity and P = 0.93 for sensitivity). Conclusions: Fourth‐generation EC offers acceptable diagnostic accuracy and reliability in both experts and non‐experts, especially when diagnosing SCC lesions. [ABSTRACT FROM AUTHOR]

Objectives: Endoscopic pressure study integrated system (EPSIS) is a novel diagnostic tool for gastroesophageal reflux disease (GERD). EPSIS has been developed to evaluate lower esophageal sphincter function by monitoring the intragastric pressure (IGP) while insufflating the stomach during gastroscopy. Based on previous data, EPSIS could diagnose GERD with good accuracy by assessing IGP waveform pattern. This study aimed to further characterize the waveform to improve the diagnostic yield of EPSIS. Methods: We conducted a retrospective analysis of patients with typical GERD symptoms who underwent both EPSIS and 24‐h impedance‐pH monitoring (MII‐pH) at a single tertiary referral center from October 2018 to May 2020. EPSIS was performed by using a through‐the‐scope catheter connected to the pressure measuring system (TR‐W550, TR‐TeH08, AP‐C35; Keyence, Osaka, Japan) to monitor IGP. Abnormal acid reflux was defined as acid exposure time (AET) over 6.0%. Pressure waveform was characterized as follows: (i) Basal IGP, (ii) Maximum IGP, (iii) Pressure difference, (iv) Gradient of the waveform. Results: A total of 57 patients with GERD symptoms were analyzed. Twenty‐one patients presented abnormal AET on MII‐pH. Among EPSIS parameters, pressure difference during insufflation correlated with AET (ρ = −0.66, P < 0.01) and showed the best diagnostic accuracy for AET with the cutoff value of 4.7 mmHg (area under the curve [AUC], 0.87). The gradient of EPSIS waveform also revealed good diagnostic accuracy for abnormal AET with the cutoff value of 0.07 mmHg/s (AUC, 0.81). Conclusions: Endoscopic pressure study integrated system waveform parameters, especially pressure difference, presented high diagnostic accuracy for the presence of abnormal acid reflux. [ABSTRACT FROM AUTHOR]

Endoscopic pressure study integrated system (EPSIS) is a novel tool for the diagnosis of gastroesophageal reflux disease. It enables the evaluation of the function of the lower esophageal sphincter by monitoring intragastric pressure (IGP) while insufflating the stomach during esophagogastroduodenoscopy. EPSIS can predict abnormal acid reflux with high accuracy based on previous studies. IGP was measured by inserting through the working channel of the scope an intragastric catheter connected to a pressure measuring device. Herein, we assess the feasibility of an updated EPSIS system, which can be performed just by connecting a flush tube to the working channel. This method does not require inserting foreign objects in the stomach and spares catheter insertion in order to simplify the procedure and reduce costs. A single‐center pilot study was conducted to evaluate the association between catheter‐based EPSIS and the updated EPSIS. The results of EPSIS in 20 patients who underwent both methods were assessed. In all cases, the waveform pattern of IGP measured by catheter‐based EPSIS and updated EPSIS was consistent with 15 uphill pattern and five flat pattern. Intraobserver agreement of waveform pattern was perfect between two examiners with kappa value = 1. Intraclass correlation coefficient (ICC) for intraobserver reliability for maximum IGP was excellent with 0.91 (95% confidence interval [CI] of 0.77 < ICC < 0.96) and for pressure gradient was also good with 0.89 (95% CI of 0.71 < ICC < 0.95). In conclusion, our study suggests that the updated EPSIS can be performed without the use of a catheter. [ABSTRACT FROM AUTHOR]

Objectives: Per‐oral endoscopic myotomy (POEM) is a safe and effective treatment for achalasia and esophageal motility disorders. The role of second‐look endoscopy (SE) on postoperative day 1 has not been examined. This study aimed to evaluate the findings and need of SE after POEM. Methods: This is a single‐center, retrospective study. All consecutive patients who underwent POEM and SE on postoperative day 1 between December 2017 and September 2019 were included. The primary endpoint was the rate of newly‐detected adverse events (nAE) during SE that required endoscopic intervention or deviation from the normal postoperative course. Multivariate logistic regression was used to identify predictors of nAE. Results: Four‐hundred‐ninety‐seven patients (mean age, 50.3 years; female, 49.9%) were included. SE identified abnormal findings in a total of 71 patients (14.3%). nAE which required endoscopic intervention or deviation from the normal postoperative course were identified in 12 patients (2.4%): eight (1.6%) entry site dehiscence; two (0.4%) submucosal hemorrhage or hematoma; and two (0.4%) dehiscence of an intraoperative perforation site after endoclip closure. Other findings such as mucosal thermal damage without perforation and small submucosal hematoma were found in 54 patients (10.9%) and five patients (1.0%), respectively. Multivariate analysis showed that longer operation time and intraoperative adverse events (AE) were associated with clinically significant nAE during SE. Conclusions: Second‐look endoscopy can detect and treat nAE that may lead to severe AE. Thus, SE should be highly considered before starting oral ingestion in all cases, and especially in those who present an intraoperative AE and longer operation time. [ABSTRACT FROM AUTHOR]

Objectives: Some patients with gastroesophageal reflux disease (GERD) are refractory to proton pump inhibitor (PPI) therapy. Anti‐reflux mucosectomy (ARMS) is a minimally invasive endoscopic procedure for treatment of GERD. In this study, we retrospectively evaluated the outcomes of ARMS performed in patients with PPI‐refractory GERD at our institution. Methods: A total of 109 patients with PPI‐refractory GERD who underwent ARMS were retrospectively reviewed. Pre‐ and post‐ARMS questionnaire scores, acid exposure time (AET), DeMeester score, proximal extent, and PPI discontinuation rate were compared. Results: There was a significant improvement in the symptom score (P < 0.01) and 40–50% of patients were able to discontinue PPI after ARMS. In patients who were followed up for 3 years, sustained improvement in subjective symptoms was observed. AET and DeMeester score significantly improved after ARMS (P < 0.01); however, there was no significant improvement in proximal extent (P = 0.0846). Conclusions: Anti‐reflux mucosectomy is an effective minimally invasive therapy for patients with PPI‐refractory GERD. The therapeutic efficacy is attributable to suppression of acid backflow due to contraction of the scar tissue in cardia. [ABSTRACT FROM AUTHOR]

Objectives: The endoscopic pressure study integrated system (EPSIS) is a novel diagnostic tool for gastroesophageal reflux disease (GERD) by monitoring intragastric pressure (IGP). Evaluation of the lower esophageal sphincter (LES) function may be achieved endoscopically by utilizing this newly developed diagnostic tool. This study aimed to evaluate the association between EPSIS results and gastroesophageal reflux‐related diseases, e.g., erosive esophagitis (EE) and Barrett's esophagus (BE). Methods: This was a retrospective, single‐center study. All patients who underwent EPSIS between November 2016 and July 2018 were included. EPSIS was performed during esophagogastroduodenoscopy with a dedicated electronic device and a through‐the‐scope catheter. The maximum IGP (IGP‐max) and IGP waveform pattern (flat or uphill) were recorded with this system. Evaluation of an EE and BE was based on the Los Angeles classification and Prague classification, respectively. Results: A total of 104 patients were enrolled; 29 (28%) had EE and 42 (40%) had BE. Patients with EE had lower IGP‐max values (16.0 vs 18.8 mmHg, P = 0.01) and an EPSIS flat pattern was seen more frequently (82.8% vs 37.3%, P < 0.001). Similarly, patients with BE displayed a lower IGP‐max (15.7 vs 19.6 mmHg, P < 0.001) and presented with an EPSIS flat pattern in a higher proportion (69% vs 37.1%, P < 0.001). These differences remained significant on multivariate analysis. Conclusions: The EPSIS, as a novel diagnostic tool, was shown to exhibit a relation with EE and BE, implying that EPSIS is a promising modality to evaluate gastroesophageal reflux‐related diseases and LES function endoscopically. [ABSTRACT FROM AUTHOR]

Objectives: The clinical success of per‐oral endoscopic myotomy (POEM) has led to the development of a new field of 'submucosal endoscopy'. This study aimed to evaluate the safety, efficacy, and limitations of per‐oral endoscopic tumor resection (POET) in the management of submucosal tumors (SMTs) in the esophagus and the gastric cardia. Methods: POET was performed in 47 patients from January 2011 to December 2017. The indication for POET was SMTs ≤ 30 mm in minor axis diameter. Patient and tumor characteristics (age, gender, tumor location, size, and histology), operative and clinical results of POET (procedure time and completion rate, en bloc resection rate, length of hospitalization, adverse events and tumor recurrence) were analyzed retrospectively. Results: POET was successfully completed in 43 patients (91.5%) without any major adverse events (Clavien‐Dindo IIIb‐IV). Four patients required conversion to an open surgical procedure due to suboptimal visualization during POET. Four patients underwent piecemeal resection of their SMTs including GISTs. Median follow‐up was 44 months (10–96 months), during that time, there were no incidences of tumor recurrence. Tumors that had a minor axis diameter > 30 mm or a tumor mass index (TMI) [major axis diameter (mm) × minor axis diameter (mm)] >1000 had a high likelihood of being converted to surgical resection. Conclusions: POET is a safe and effective treatment for SMTs. However, in patients where the minor axis diameter is > 30 mm or the TMI > 1000, surgical excision should be considered. Furthermore, application of POET for SMTs with malignant potential should be carefully considered to ensure optimal oncologic outcomes. [ABSTRACT FROM AUTHOR]

Background: Peroral endoscopic myotomy (POEM) for achalasia is technically challenging to carry out in patients with type III, multiple prior treatments, prior myotomy, and sigmoid type. Herein, we present a series of consecutive patients with complex achalasia and introduce the POEM difficulty score (PDS). Aim: To demonstrate the application and discuss the utility of PDS and present the feasibility, safety, and efficacy of POEM in complex achalasia patients. Methods: Forty consecutive POEM were carried out with 28 meeting the criteria for complex achalasia. Primary outcome was clinical success (Eckardt score ≤3) at a minimum of 3 months follow‐up. Secondary outcomes included adverse events, procedural velocity and PDS. Results: Twenty‐eight complex and 12 non‐complex POEM procedures were carried out with 100% and 92% clinical success, respectively, without any major adverse events with a median follow up of 15 months (complex) and 8 months (non‐complex). Mean velocities for non‐complex, type III, prior myotomy, ≥4 procedures and sigmoid type were as follows: 4.4 ± 1.6, 4.8 ± 1.5, 5.9 ± 2.2, 6.9 ± 2.2 and 8.2 ± 3.2 min/cm, respectively. Median PDS for non‐complex, type III, prior myotomy, ≥4 treatments and sigmoid type were 1 (0–3), 2 (0–4), 2.5 (1–6), 3 (2–6) and 3.5 (1–6), respectively. PDS was shown to correlate well with procedural velocity with a correlation coefficient of 0.772 (Spearman's P < 0.001). Conclusions: PDS identifies the factors that contribute to challenging POEM procedures and correlates well with procedural velocity. The order of increasing difficulty of POEM in complex achalasia appears to be type III, prior myotomy, ≥4 treatments and sigmoid type. [ABSTRACT FROM AUTHOR]

Peroral endoscopic myotomy (POEM) is a novel clinical technique developed in Japan used to treat esophageal achalasia and esophageal motility disorders. This technique has been rapidly accepted and widely disseminated throughout our clinical practice because of its low invasiveness, technical novelty, and high efficacy. Since the advent of POEM, there have been no clinical guidelines that clearly indicated its standard of care, and these guidelines have been anticipated both nationally and internationally by clinicians who engage in POEM practice. In 2017, to meet these needs, the Japan Gastroenterological Endoscopy Society (JGES) launched the guideline committee for POEM. Based on the guideline development process proposed by the Medical Information Network Distribution Service (MINDS), the guideline committee initially created research questions on POEM and conducted a systematic review and meta‐analysis on each topic. The clinical research extracted from databases for these clinical questions and the systematic review mainly comprised a few retrospective studies with a small number of participants and short trial periods; hence, the strength of the evidence and recommendations derived from these results was low. Throughout this process, the guideline committee met thrice: once on May 13, 2017, and again on September 17, 2017, to formulate the draft. A consensus meeting was then held on January 14, 2018, in Tokyo to establish the guideline statements and finalize the recommendations using the modified Delphi method. This manuscript presents clinical guidelines regarding current standards of practice and recommendations in terms of the nine chief topics in POEM. [ABSTRACT FROM AUTHOR]

Background and Aim Endoscopy, barium esophagram and manometry are used in the diagnosis of achalasia. In the case of early achalasia, characteristic endoscopic findings are difficult to recognize. As a result, the diagnosis of achalasia is often made several years after symptom onset. Therefore, we examined the endoscopic findings of the cardiac orifice in achalasia and propose a new classification. Methods A total of 400 patients with spastic esophageal motility disorders who underwent peroral endoscopic myotomy (POEM) at our hospital between March 2014 and August 2015 were screened for this study. Champagne glass sign (CG) was defined as when the distal end of the lower esophageal sphincter relaxation failure (LESRF) was proximal to the squamocolumnar junction (SCJ) and the SCJ was dilated in the retroflex view. Specifically, CG-1 was defined as a distance from the SCJ to the lower end of LESRF of <1 cm, and CG-2 was defined as a distance ≥1 cm. Results CG-0 was seen in 73 patients (28.0%), whereas the CG sign was seen in 186 patients (71.3%), of whom 170 (65.1%) were CG-1 and 16 (6.1%) were CG-2. Conclusions The CG sign is often observed in esophageal achalasia patients. CG-0 (equal to Maki-tsuki) was observed in 28.0% of achalasia patients only. Its absence with dilated SCJ cannot be used to rule out achalasia. Barium esophagram and manometry should be done if esophageal achalasia is strongly suspected. [ABSTRACT FROM AUTHOR]

Many preclinical studies have shown the potential of adenovirus-based cancer gene therapy. However, successful translation of these promising results into the clinic has not yet been achieved. Pancreatic ductal adenocarcinoma (PDAC) is characterized by abundant desmoplastic stroma, and tumor-stromal cell interactions play a critical role in tumor progression. Therefore, we hypothesized that tumor-stroma interactions reduce the efficacy of adenoviral therapy. We investigated the effect of fibroblasts on adenovirus-based gene therapy using SUIT-2 and PANC-1 pancreatic cancer cells cultured with or without fibroblast-conditioned culture supernatant then infected with Ad-LacZ. After 48 h, the cells were stained for β-galactosidase. The results showed that the number of β-galactosidase-positive cells was significantly reduced after culture with fibroblast-conditioned supernatant ( P < 0.05). Because the hepatocyte growth factor (HGF)/MET pathway plays an important role in tumor-stroma interactions we next investigated the involvement of this pathway in tumor-stroma interactions leading to the decreased efficacy of adenoviral therapy. SUIT-2 cells were cultured with or without SU11274 (a MET inhibitor) and/or fibroblast-conditioned culture supernatant, then infected with Ad-GFP. After 48 h, GFP-positive cells were counted. The number of GFP-positive cells in cultures containing fibroblast-conditioned supernatant plus SU11274 was significantly greater than in cultures without SU11274. In conclusion, our results suggest that stromal cells in PDAC reduce the efficacy of adenoviral therapy through a mechanism involving the HGF/MET pathway. Control of such tumor-stroma interactions may lead to improvements in adenoviral gene therapy for PDAC. ( Cancer Sci 2011; 102: 484-491) [ABSTRACT FROM AUTHOR]

( Cancer Sci 2010; 101: 735–742) Adenovirus-mediated gene therapy shows promise for cancer therapy, but transgene expression of replication-defective adenovirus may be low and transient in clinical settings. Recent reports have shown that the use of a conditionally replication-competent adenovirus (CRAd) enhanced the gene transduction of a replication-defective adenovirus vector. The control of tumor–stromal interactions has also been determined to be important in cancer therapy. In this study, we investigated the effect of the human telomerase reverse transcriptase (hTERT)-CRAd, Ad5/3hTERTE1, which possesses the tumor-specific hTERT promoter with the chimeric fiber 5/3, on the transgene expression and therapeutic efficacy of a replication-defective adenovirus vector expressing NK4 under the control of the CMV promoter, Ad-NK4. In addition, we established a new strategy to target both cancer cells and cancer–stromal interactions. Human pancreatic cancer cells were infected with Ad-NK4 and either Ad5/3hTERTE1 (CRAd-combination group) or Ad5/3hTERTLuc (control-combination group). In the CRAd-combination group, Ad-NK4-delivered transgene expression was increased, leading to an enhanced inhibitory effect on the invasion of cancer cells. In in vivo experiments, NK4 expression within tumors and its inhibitory effect on tumor growth, angiogenesis, and metastasis were enhanced in the CRAd-combination group. These results suggest that hTERT-CRAd enhances the transgene expression and therapeutic efficacies of Ad-NK4, possibly through the in-trans replication of Ad-NK4 induced by adenovirus E1 derived from co-infected hTERT-CRAd. This approach may be a promising combination therapy against advanced pancreatic cancer. [ABSTRACT FROM AUTHOR]

Adenovirus-mediated gene therapy is a promising approach for the treatment of pancreatic cancer. We previously reported that radiation enhanced adenovirus-mediated gene expression in pancreatic cancer, suggesting that adenoviral gene therapy might be more effective in radioresistant pancreatic cancer cells. In the present study, we compared the transduction efficiency of adenovirus-delivered genes in radiosensitive and radioresistant cells, and investigated the underlying mechanisms. We used an adenovirus expressing the hepatocyte growth factor antagonist, NK4 (Ad-NK4), as a representative gene therapy. We established two radioresistant human pancreatic cancer cell lines using fractionated irradiation. Radiosensitive and radioresistant pancreatic cancer cells were infected with Ad-NK4, and NK4 levels in the cells were measured. In order to investigate the mechanisms responsible for the differences in the transduction efficiency between these cells, we measured expression of the genes mediating adenovirus infection and endocytosis. The results revealed that NK4 levels in radioresistant cells were significantly lower ( P < 0.01) than those in radiosensitive cells, although there were no significant differences in adenovirus uptake between radiosensitive cells and radioresistant cells. Integrin β3 was up-regulated and the Coxsackie virus and adenovirus receptor was down-regulated in radioresistant cells, and inhibition of integrin β3 promoted adenovirus gene transfer. These results suggest that inhibition of integrin β3 in radioresistant pancreatic cancer cells could enhance adenovirus-mediated gene therapy. ( Cancer Sci 2009; 100: 1902–1907) [ABSTRACT FROM AUTHOR]

Adenovirus-mediated gene therapy combined with chemotherapeutic agents is expected to represent a new approach for treating pancreatic cancer. However, there have been no reports of definitive effects of chemotherapeutic agents on adenovirus-mediated gene therapies. In the present study, we investigated the effects of chemotherapeutic agents on the transduction efficiency of an adenovirus-based gene therapy. Adenovirus (Ad-NK4) expressing NK4, which acts as a hepatocyte growth factor antagonist, was used as a representative gene therapy. Pancreatic cancer cells infected with Ad-NK4 were treated with chemotherapeutic agents (5-fluorouracil [5FU], cisplatin or etoposide), and the NK4 levels in their culture media were measured. To examine the effects of chemotherapeutic agents in vivo, Ad-NK4 was administered to subcutaneous tumors in mice after treatment with the agents, and the tumor NK4 levels were measured. The NK4 levels in culture media from cells treated with 5FU, cisplatin and etoposide were 5.2-fold ( P = 0.026), 6-fold ( P < 0.001) and 4.3-fold ( P < 0.001) higher than those of untreated cells, respectively. The chemotherapeutic agents also increased Ad-NK4 uptake. The NK4 levels in tumors treated with 5FU, cisplatin and etoposide were 5.4-fold ( P = 0.006), 11.8-fold ( P < 0.001) and 4.9-fold ( P = 0.017) higher than those in untreated tumors, respectively. The present findings suggest that chemotherapeutic agents significantly improve the efficiency of adenovirus-mediated gene transfer in pancreatic cancer. Furthermore, they will contribute to decreases in the adenovirus doses required for gene transfer, thereby controlling the side-effects of adenovirus infection in normal tissues. ( Cancer Sci 2009; 100: 722–729) [ABSTRACT FROM AUTHOR]

Clinicians frequently require cytopathological assessment of tumor samples for preoperative diagnosis, but in some specimens, diagnosis remains inconclusive after cytological examination. To date, several molecular markers, including human telomerase reverse transcriptase (hTERT), have been assessed for the ability to detect malignancy. However, analyses using whole cytological specimens are generally affected by contamination of untargeted cells. The present study investigated the feasibility of more sensitive examination by quantitative mRNA analysis of target cells microdissected from cytological specimens. Laser capture microdissection (LCM) was used to obtain target cells from cytological specimens. hTERT mRNA levels were then measured in target cells by quantitative real-time RT-PCR (qRT-PCR). The effect of RNA fragmentation on qRT-PCR was also assessed. Total RNA from cytological specimens was sometimes fragmented to a large degree. To avoid the effect of RNA fragmentation, gene specific priming and PCR primers generating short PCR products were used and no difference in delta Ct values between fragmented and non-fragmented RNA were found. hTERT mRNA levels were measured in cells microdissected from 33 cytological specimens. The levels of hTERT mRNA were significantly higher in malignant cases compared to those in non-malignant cases ( P = 0.0003). The sensitivity was 96.2%, even when the specificities were 100%. High levels of hTERT mRNA were also found in three cases that were not diagnosed as malignant by cytological examination. Quantitative assessment of hTERT mRNA levels in cells microdissected from cytological specimens is a potential diagnostic tool to potentiate cytological examination in diagnosing malignancy. ( Cancer Sci 2008; 99: 2244–2251) [ABSTRACT FROM AUTHOR]

Background. Bile juice plays a major role in duodenogastroesophageal reflux (DGERD). Several devices to directly measure the bile concentration have been proposed. We aimed to ex-vivo evaluate the bile concentration by narrow band imaging (NBI). Method. From six surgical cholecystectomies, the content of the gallbladders was aspirated and the total biliary acid (TBA) concentration was evaluated. 2 mL was employed for serial twofold dilutions. Each dilution was scoped. Images on white light (WL) and NBI were captured and grouped accordingly to NBI-appearance and TBA-concentration. Results. Nondiluted bile had a TBA-concentration of 61965 ± 32989 μmol/L. Final dilution (1 : 4096) had 1.16 μmol/L. NBI and correspondent WL images were grouped into seven groups, and an NBI/Bile scale was created. Conclusion. The scale showed that not only NBI scale but also white light scale could be useful to predict the bile concentration. This initial study shows that NBI has a potential role in the detection of DGERD and further investigation is warranted to distinguish the presence and the concentration of bile, especially at very low TBA concentrations. [ABSTRACT FROM AUTHOR]

A reply to "Second-look endoscopy after POEM for all, some or none... More you see, the more you find!" What are the factors for detecting adverse events in second-look endoscopy after per-oral endoscopic myotomy (POEM)? However, further analysis in the patient cohort showed no significant difference in symptom duration between cases with nAE and those without. [Extracted from the article]

Objectives Methods Results Conclusion 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.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.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.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. [ABSTRACT FROM AUTHOR]

Objectives Methods Results Conclusion 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.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.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).The results supported the use of EPSIS as an effective diagnostic tool for assessing the effect of POEM. [ABSTRACT FROM AUTHOR]