Long-term efficacy of antireflux mucosectomy in patients with refractory gastroesophageal reflux disease.

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.

Clinical outcomes of anti-reflux mucosal ablation for gastroesophageal reflux disease: An international bi-institutional study.

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.

Endoscopic carbon dioxide insufflation tolerance test on the anal sphincter for anorectal hypofunction: a pilot and feasibility study.

Background: Anorectal function deteriorates with age. The diagnostic performance of the endoscopic pressure study integrated system (EPSIS), an endoscopic carbon dioxide (CO2) insufflation stress test of the lower esophageal sphincter has been previously evaluated as a diagnostic tool for gastroesophageal reflux disease. We aimed to evaluate the applicability of EPSIS in improving anorectal function. We hypothesized that EPSIS can be applied to the diagnosis of lower gastrointestinal tract disorders. Methods: This was a pilot, single-center, retrospective study using prospectively collected data between December 2021 and March 2022. It was designed to evaluate the differences in EPSIS rectal pressure measurements between older (≥80 years) and younger (<80 years) patients. At the end of the screening colonoscopy, the colonoscope was fixed in a retroflex position. When bowel movement was observed, CO2 was insufflated to the point where gas leakage occurred through the anus. The measured maximum pressure was defined as EPSIS-rectal pressure max (EPSIS-RP max) and compared between the groups. Results: Overall, 30 patients were included and examined. The median ages of the <80 and ≥80 years' groups were 53 (range: 27-79) and 82 (range: 80-94) years, respectively, with corresponding median measured EPSIS-RP max of 18.7 (range: 8.5-30.2) and 9.8 (range: 5.4-22.3) mmHg (P<0.001). Conclusions: Measurement of maximum rectal pressure illustrates the age-related decline in physiological anorectal function. Future studies should consider a loading test using EPSIS to quantify the decline in anorectal function and use it as a routine tool for screening and adjunctive diagnosis of anorectal hypofunction.

Real-life effectiveness of indacaterol/glycopyrronium/mometasone for symptomatic relief of cough after switching from inhaled corticosteroid/long-acting ß2-agonist therapy in patients with asthma: REACH study design.

Cough is a major symptom in patients with asthma and poses a significant burden compared with other asthma symptoms. However, there are no approved treatments in Japan, developed to specifically treat cough in patients with asthma. We present the design of REACH, an 8-week real-life study, which will evaluate the efficacy of a combination of indacaterol acetate, glycopyrronium bromide and mometasone furoate (IND/GLY/MF) in asthmatic patients with cough refractory to medium-dose inhaled corticosteroid/long-acting ß2-agonist (ICS/LABA). Patients with asthma (age ≥20 to <80 years) with a cough visual analogue scale (VAS) ≥40 mm will be randomised 2:1:1 to receive IND/GLY/MF medium-dose 150/50/80 µg once daily or step-up to a high-dose regimen of fluticasone furoate/vilanterol trifenatate (FF/VI) 200/25 µg once daily or budesonide/formoterol fumarate (BUD/FM) 160/4.5 µg four inhalations twice daily during the 8-week treatment period. The primary objective is to demonstrate the superiority of IND/GLY/MF medium-dose over high-dose ICS/LABA in terms of cough-specific quality of life after 8 weeks. The key secondary objective is to demonstrate the superiority of IND/GLY/MF in terms of subjective assessment of cough severity. Cough frequency (VitaloJAK cough monitor) and capsaicin cough receptor sensitivity will be evaluated in eligible patients. Cough VAS scores, fractional exhaled nitric oxide, spirometry and blood tests, and the Asthma Control Questionnaire-6, Cough and Sputum Assessment Questionnaire, and Japanese version of the Leicester Cough Questionnaire will be evaluated. REACH will provide valuable evidence on whether a switch to IND/GLY/MF medium-dose or step-up to high-dose ICS/LABA is beneficial for patients with persistent cough despite treatment with medium-dose ICS/LABA.

Learning curve for peroral endoscopic myotomy in therapeutic endoscopy experts and nonexperts: Large single-center experience.

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.

Association between endoscopic pressure study integrated system (EPSIS) and high-resolution manometry.

Background and study aims The endoscopic pressure study integrated system (EPSIS), a novel diagnostic tool for gastroesophageal reflux disease (GERD), allows evaluation of the anti-reflux barrier using endoscopy by monitoring the intragastric pressure (IGP) during insufflation. In this study, we evaluated the association between EPSIS results and lower esophageal sphincter (LES) function measured by high-resolution manometry (HRM) to elucidate whether EPSIS can evaluate the LES function. Patients and methods A retrospective, single-center study of patients with GERD symptoms who underwent endoscopy, pH-impedance monitoring, EPSIS, and HRM was conducted. The primary outcome was basal LES pressure and the secondary outcomes were end-respiratory LES pressure and integrated relaxation pressure (IRP). As EPSIS parameters, the following were measured: 1) pressure difference (mmHg), the difference between maximum and basal IGP; and 2) pressure gradient (mmHg/s), calculated by dividing pressure difference by the insufflating time. Pressure difference < 4.7 mmHg or pressure gradient < 0.07 mmHg/s was defined as an EPSIS GERD pattern. Results Forty-seven patients (median age: 53 years, 37 female) were analyzed. Pressure difference and pressure gradient significantly correlated with basal LES pressure (ρ = 0.29; P =  0.04 and ρ = 0.29; P =  0.04). Patients with EPSIS GERD pattern showed significantly lower basal LES pressure [13.2 (4.8-26.6) vs 25.3 (10.4-66.7) mmHg, P =  0.002], lower end-respiratory LES pressure [8.5 (1.1-15.9) vs 15.5 (1.9-43.9) mmHg, P =  0.019] and lower IRP [5.9 (1.0-12.0) vs 9.8 (1.3-17.8) mmHg, P =  0.020]. Conclusions This study showed a close association between EPSIS results and LES pressures measured by HRM. This indicates that EPSIS can evaluate the LES function during endoscopy and endorse the role of EPSIS as a diagnostic tool for GERD.

Comparison of scope holding sign on endoscopy and lower esophageal sphincter contraction on high-resolution manometry: A pilot study.

Objectives: Lower esophageal sphincter (LES) plays a key role in gastroesophageal reflux disease (GERD) pathogenesis. In retroflexion and under sufficient insufflation, it can be seen how the lower esophagus grasps the endoscope, which we named scope holding sign (SHS). This study aimed to compare the SHS and LES pressure on high-resolution manometry (HRM), to elucidate whether the sphincter can be visualized endoscopically. Methods: This was a single-center, prospective pilot study. Patients with symptoms of GERD, who underwent endoscopy and HRM between February 2021 and April 2021, were included. A manometry catheter and an ultra-slim endoscope were inserted, and the resting LES pressure was measured. The lower esophagus holding (SHS-positive) and releasing (SHS-negative) the endoscope and catheter were observed. The LES pressures during SHS-positive and SHS-negative were compared. Results: Eleven patients (median age: 57 years; eight men) with normal esophageal motility were analyzed. The median LES pressure in SHS-positive was significantly higher than the resting LES pressure (40.4 [22.9-74.0] vs. 25.9 [2.0-66.7] mm Hg; p = 0.001) and the LES pressure in SHS-negative (4.6 [1.5-9.3]; p = 0.001). Furthermore, the LES pressure in SHS-negative was significantly lower than the resting LES pressure (4.6 [1.5-9.3] vs. 25.9 [2.0-66.7] mm Hg; p = 0.005). Conclusions: This study demonstrated that the SHS parallels LES pressure, indicating that the sphincter can be observed endoscopically. This may enable us to evaluate LES function during endoscopy in patients with GERD, thus, deserving further evaluation in future studies.

Novel Mechanism by a Bis-Pyridinium Fullerene Derivative to Induce Apoptosis by Enhancing the MEK-ERK Pathway in a Reactive Oxygen Species-Independent Manner in BCR-ABL-Positive Chronic Myeloid Leukemia-Derived K562 Cells.

In the treatment of breakpoint cluster region-Abelson (BCR-ABL)-positive chronic myeloid leukemia (CML) using BCR-ABL inhibitors, the appearance of a gatekeeper mutation (T315I) in BCR-ABL is a serious issue. Therefore, the development of novel drugs that overcome acquired resistance to BCR-ABL inhibitors by CML cells is required. We previously demonstrated that a bis-pyridinium fullerene derivative (BPF) induced apoptosis in human chronic myeloid leukemia (CML)-derived K562 cells partially through the generation of reactive oxygen species (ROS). We herein show that BPF enhanced the activation of the mitogen-activated protein kinase/extracellular signal-regulated kinase kinase-extracellular signal-regulated kinase (MEK-ERK) pathway in a ROS-independent manner. BPF-induced apoptosis was attenuated by trametinib, suggesting the functional involvement of the MEK-ERK pathway in apoptosis in K562 cells. In addition, the constitutive activation of the MEK-ERK pathway by the enforced expression of the BRAFV600E mutant significantly increased the sensitivity of K562 cells to BPF. These results confirmed for the first time that BPF induces apoptosis in K562 cells through dual pathways-ROS production and the activation of the MEK-ERK pathway. Furthermore, BPF induced cell death in transformed Ba/F3 cells expressing not only BCR-ABL but also T315I mutant through the activation of the MEK-ERK pathway. These results indicate that BPF is as an effective CML drug that overcomes resistance to BCR-ABL inhibitors.

Once-daily, single-inhaler indacaterol/mometasone versus twice-daily salmeterol/fluticasone in Asian patients with inadequately controlled asthma: post hoc pooled analysis from PALLADIUM and IRIDIUM studies.

OBJECTIVE: PALLADIUM and IRIDIUM studies demonstrated efficacy and safety of indacaterol/mometasone (IND/MF) versus salmeterol/fluticasone (SAL/FLU). This post hoc analysis of pooled data from PALLADIUM and IRIDIUM studies evaluated efficacy and safety of IND/MF versus SAL/FLU in Asian patients with inadequately controlled asthma. METHODS: Both studies were Phase III, 52-week, randomized, double-blind, active-controlled that included patients with predicted pre-bronchodilator FEV1 (PALLADIUM, ≥50%-<85%; IRIDIUM, <80%), ACQ-7 score ≥1.5. Patients treated with IND/MF high- (150/320 µg) or medium-dose (150/160 µg) or SAL/FLU high-dose (50/500 µg) were included. Lung function, asthma control, and asthma exacerbations were evaluated. RESULTS: In total, 323 patients (IND/MF high-dose, n = 107; IND/MF medium-dose, n = 106, SAL/FLU high-dose, n = 110) were included. IND/MF high-dose showed improvement in trough FEV1 versus SAL/FLU high-dose at Weeks 26 (Δ, 42 mL; 95% CI, -35 to 120 mL), and 52 (Δ, 41 mL; 95% CI, -37 to 120 mL). IND/MF high-dose exhibited numerically greater improvement in ACQ-7 score versus SAL/FLU high-dose at Weeks 26 (Δ, -0.215; 95% CI, -0.385 to -0.044) and 52 (Δ, -0.176; 95% CI, -0.348 to -0.005). Improvements in trough FEV1 and ACQ-7 score were comparable between IND/MF medium-dose and SAL/FLU high-dose. IND/MF high- and medium-dose showed reductions in moderate or severe (45%; 30%), severe (39%; 41%), and all (9%; 25%) exacerbations, respectively, versus SAL/FLU high-dose over 52 weeks. All treatments were well tolerated. CONCLUSIONS: Once-daily, single-inhaler IND/MF high-dose improved lung function with better asthma control, reduced asthma exacerbations with comparable safety versus twice-daily SAL/FLU high-dose. IND/MF medium-dose showed comparable outcomes to SAL/FLU high-dose at a reduced steroid dose.

A novel endoscopic purse-string suture technique, "loop 9", for gastrointestinal defect closure: a pilot study.

BACKGROUND : This study aimed to assess the feasibility and efficacy of the novel loop 9 method of gastrointestinal (GI) defect closure. METHODS : 20 patients underwent a GI procedure that required defect closure. Loop 9 can be delivered through a single instrument channel (3.2 mm) and released at the defect site. After it has been anchored by two clips positioned on opposite sides of the defect edge, the loop 9 is tightened by pulling the end of the suture intraluminally using biopsy forceps. Additional clips are placed to achieve complete closure. The primary outcome was complete closure rate. The secondary outcomes were closure time, sustained closure rate, and adverse events. RESULTS : Complete closure was achieved in 100 % of cases. The mean size of the mucosal defects was 17.5 mm (range 10-55 mm). The median closure time was 14 minutes. The sustained closure rate was 90 %. No adverse events were noted. CONCLUSIONS : The loop 9 technique is feasible and effective in achieving complete and sustained closure of therapeutic endoscopy-related GI defects.

A bis-pyridinium fullerene derivative induces apoptosis through the generation of ROS in BCR-ABL-positive leukemia cells.

A fusion protein, Breakpoint cluster region-Abelson (BCR-ABL) is responsible for the development of chronic myeloid leukemia (CML) and acute lymphocytic leukemia (ALL). Inhibitors against BCR-ABL are effective for the treatment of leukemia; however, a gatekeeper mutation (T315I) in BCR-ABL results in resistance to these inhibitors, which markedly impedes their efficacy. We herein demonstrated that a bis-pyridinium fullerene derivative (BPF) significantly induced apoptosis in human CML-derived K562 cells and ALL-derived SUP-B15 cells via the generation of reactive oxygen species (ROS). BPF reduced the expression of Bcr-Abl mRNA by inhibiting expression of c-Myc through ROS production. BPF also accelerated protein degradation of BCR-ABL through ROS production. Furthermore, BPF down-regulated the expression of not only BCR-ABL but also T315I-mutated BCR-ABL in ROS-dependent manner. As a result, BPF effectively induced apoptosis in transformed Ba/F3 cells expressing both BCR-ABL and T315I-mutated BCR-ABL. Collectively, these results indicate the potential of BPF as an effective leukemia drug that overcomes resistance to BCR-ABL inhibitors.

Diagnosis of congenital esophageal stenosis in adults and treatment with peroral endoscopic myotomy.

BACKGROUND: Congenital esophageal stenosis (CES) in adults is a rare disorder that can present as achalasia, particularly in the distal esophagus. We describe the salient features of CES in adults and identify the feasibility and short-term outcomes of peroral endoscopic myotomy (POEM) for CES. METHODS: In this retrospective, single-center case series, we included 6 patients with a "misdiagnosis" of achalasia established elsewhere, ultimately diagnosed with CES and referred to our institution for POEM. Symptom improvement (clinical success rate), defined as an Eckardt Symptom Score (ESS) of <3 at 2-month follow up was assessed. RESULTS: Six patients (median age: 40 [range: 18-58] years; 4 males) were included. A long-standing history of dysphagia, ring-shaped stenosis on endoscopic examination, "lopsided hourglass" sign on barium esophagogram, and high-resolution manometry findings indicated by a compartmentalized intrabolus pressure pattern with distinction between the stenotic area and the lower esophageal sphincter were the salient features identified. POEM could not be completed in the first 2 cases due to technical challenges. All subsequent 4 patients who underwent successful POEM, exhibited improved ESS of ≤3 (clinical success rate 100%) at 2 months post-POEM. CONCLUSIONS: Along with identification of salient features on several diagnostic modalities, a differential diagnosis of CES in adults must be considered in patients presenting with long-standing history of dysphagia arising from childhood and persisting into adulthood. Although favorable short-term outcomes of POEM were achieved, further evaluation is still warranted, and an inexperienced operator should not attempt POEM on CES patients due to its technical difficulties.

Long-term clinical results of per-oral endoscopic myotomy (POEM) for achalasia: First report of more than 10-year patient experience as assessed with a questionnaire-based survey.

Background and study aims Since per-oral endoscopic myotomy (POEM) was introduced in 2010, it has become accepted as one of the standard treatments for esophageal achalasia worldwide. This study aimed to present long-term clinical results of POEM over 10 years and evaluate the technique and outcomes at the institution where it was first used in clinical settings. Patients and methods Questionnaire-based surveys were sent to patients who received POEM in our institution from September 2008 to May 2010. Patient demographics and procedural outcomes and open-ended questions were posed about the postoperative courses, including symptom improvement and recurrence, additional treatments, and post-POEM gastroesophageal reflux disease (GERD) symptoms. Achalasia symptoms and post-POEM GERD symptoms were evaluated with Eckhardt scores and GerdQ systems, respectively. Results Thirty-six consecutive POEMs were performed in that period and 10-year follow-up data were obtained from 15 patients (41.7 %). Although four cases (26.7 %) required additional pneumatic balloon dilatation (PBD), reduction in post-Eckardt scores were observed in 14 cases (93.3 %). GerdQ score was positive in one patient (6.7 %). Proton pump inhibitors (PPI) were taken by four patients (26.7 %) and their symptoms were well-controlled. Conclusions Clinical results of POEM over 10 years were favorable regardless of various factors. Symptoms improved even in patients who required additional treatments, suggesting that POEM plays a significant role in treatment of achalasia.

Characterization of intragastric pressure waveform in endoscopic pressure study integrated system: Novel diagnostic device for gastroesophageal reflux disease.

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.

Importance of second-look endoscopy after per-oral endoscopic myotomy for safe postoperative management.

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.

Endoscopic treatment of proton pump inhibitor-refractory gastroesophageal reflux disease with anti-reflux mucosectomy: Experience of 109 cases.

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.

Diagnostic yield of fourth-generation endocytoscopy for esophageal squamous lesions using a modified endocytoscopic classification.

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.