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INTRODUCTION Per-oral endoscopic myotomy (POEM) has been widely adopted for the treatment of achalasia as it provides a precise, tailored myotomy in a minimally invasive endoscopic procedure. Several short-term studies and a few long-term studies have confirmed that POEM is a safe and effective treatment for achalasia. However, the long-term outcome of POEM performed by trainees is unknown. MATERIALS AND METHODS We conducted a retrospective study of all patients who underwent POEM for achalasia at our tertiary care center during December 2012 and January 2019. All procedures performed with trainees were included. The primary outcome was the clinical response to POEM, defined as an Eckardt score of

Esophagogastric junction obstruction (EGJO) post-fundoplication (PF) is difficult to identify with currently available tests. We aimed to assess the diagnostic accuracy of EGJ opening on functional lumen imaging probe (FLIP) and dilation outcome in FLIP-detected EGJO in PF dysphagia. We prospectively collected data on PF patients referred to Esophageal Clinic over 18 months. EGJO diagnosis was made by (a) endoscopist’s description of a narrow EGJ/wrap area, (b) appearance of wrap obstruction or contrast/tablet retention on esophagram, or (c) EGJ-distensibility index (DI)

Distal esophageal spasm (DES) is a rare major motility disorder in the Chicago classification of esophageal motility disorders (CC). DES is diagnosed by finding of ≥ 20% premature contractions, with normal lower esophageal sphincter (LES) relaxation on high-resolution manometry (HRM) in the latest version of CCv3.0. This feature differentiates it from achalasia type 3, which has an elevated LES relaxation pressure. Like other spastic esophageal disorders, DES has been linked to conditions such as gastroesophageal reflux disease, psychiatric conditions, and narcotic use. In addition to HRM, ancillary tests such as endoscopy and barium esophagram can provide supplemental information to differentiate DES from other conditions. Functional lumen imaging probe (FLIP), a new cutting-edge diagnostic tool, is able to recognize abnormal LES dysfunction that can be missed by HRM and can further guide LES targeted treatment when esophagogastric junction outflow obstruction is diagnosed on FLIP. Medical treatment in DES mostly targets symptomatic relief and often fails. Botulinum toxin injection during endoscopy may provide a temporary therapy that wears off over time. Myotomy through peroral endoscopic myotomy or via surgical Heller myotomy can provide long term relief in cases with persistent symptoms.

Background and objective Multiple comorbidities may contribute to high readmission rates post-transplant procedures. In this study, we aimed to assess the rates and factors associated with hospital readmissions for dyspeptic symptoms among transplant patients. Methods This was a retrospective analysis of adult patients who underwent solid organ transplants at our institution. Pregnant patients or those patients with preexisting gastroparesis were excluded from the study. Readmissions associated with the International Classification of Diseases (ICD) codes for nausea/vomiting, weight loss, failure to thrive, abdominal pain, and/or bloating were included. Factors associated with 30-day and frequent readmissions (two or more) were explored. Results A total of 931 patients with solid organ transplants were included; 54% had undergone kidney transplants while 34% were liver transplants. Of note, 30% were readmitted within the first 30 days after discharge following transplant while 32.3% had frequent readmissions. A post-transplant upper endoscopy (EGD) was performed in 34% with food residue discovered in 19% suggesting gastroparesis. However, since only 22% of these patients had a gastric emptying study, only 6% were formally diagnosed with gastroparesis, which was independently associated with both 30-day [odds ratios (OR): 2.58, 95% confidence intervals (CI): 1.42-4.69] and frequent readmissions (OR: 6.71, 95% CI: 3.45-13.10). The presence of pre-transplant diabetes (35%) was significantly associated with a diagnosis of gastroparesis following transplant (OR: 5.17, 95% CI: 2.79-9.57). The use of belatacept (OR: 0.63, 95% CI: 0.42-0.94, p=0.023) was associated with a decrease in the odds of 30-day readmissions. Conclusion A significant number of patients were readmitted due to dyspeptic symptoms after solid organ transplants. Diabetes and gastroparesis were significantly associated with higher odds of readmissions while the use of belatacept appeared to be a protective factor.

Esophagogastric junction obstruction (EGJO) post-fundoplication (PF) is difficult to identify with currently available tests. We aimed to assess the diagnostic accuracy of EGJ opening on functional lumen imaging probe (FLIP) and dilation outcome in FLIP-detected EGJO in PF dysphagia.We prospectively collected data on PF patients referred to Esophageal Clinic over 18 months. EGJO diagnosis was made by (a) endoscopist's description of a narrow EGJ/wrap area, (b) appearance of wrap obstruction or contrast/tablet retention on esophagram, or (c) EGJ-distensibility index (DI) 2.8 mmTwenty-six patients were included, of whom 17 (65%) had a low EGJ-DI. No patients had a hiatal hernia greater than 3 cm. Dysphagia was the primary symptom in 17/26 (65%). In 85% (κ = 0.677) of cases, EGJ assessment (tight vs. open) was congruent between the combination of endoscopy (n = 26) and esophagram (n = 21) vs. EGJ-DI (n = 26) on FLIP. Follow-up data were available in 11 patients who had dilation based on a low EGJ-DI (4 with 20 mm balloon and 7 with ≥ 30 mm balloon). Overall, the mean % improvement in dysphagia was 60% (95% CI 37.7-82.3%, p = 0.0001). Nine out of 11 patients, including 6 out of 7 undergoing pneumatic dilation, had improvement ≥ 50% in dysphagia (mean % improvement 72.2%; 95% CI 56.1-88.4%, p = 0.0001).Functional lumen imaging probe is an accurate modality for evaluating for EGJ obstruction PF. FLIP may be used to select patients who may benefit from larger diameter dilation.

Gastric per-oral endoscopic pyloromyotomy (GPOEM) is emerging as a promising option for the treatment of gastroparesis. This study assessed outcomes and quality of life after GPOEM for gastroparesis, performed in an endoscopy unit at a major tertiary referral center.We performed a retrospective review of patients who had undergone GPOEM from June 2015 to July 2016. Data were collected from electronic medical records and included patient demographics, endoscopy records, hospitalization records, clinic visits, and electronic messages. Scores for the Short Form 36 (SF36) and Gastroparesis Cardinal Symptom Index (GCSI) were obtained pre-procedure (16 patients), at 1 month (16 patients), at 6 months (13 patients), and at 12 months (6 patients) after the GPOEM procedure was performed.Sixteen consecutive patients, 13 women and 3 men (mean age, 44.76 ± 14.8 years), who underwent GPOEM were enrolled. GPOEM was technically successful in all cases. Thirteen of 16 (81%) patients had a significant improvement in the mean GCSI after GPOEM: 3.40 ± 0.50 before the procedure (16 patients) to 1.48 ± 0.95 (P = .0001) at 1 month (16 patients), 1.36 ± 0.9 (P .01) at 6 months (13 patients), and 1.46 ± 1.4 (P .01) at 12 months (6 patients) follow-up. Mean duration of the procedure was 49.7 ± 22.1 minutes. Mean myotomy length was 2.94 ± 0.1 cm. Mean length of hospital stay was 2.46 ± 0.7 days. No adverse events occurred with GPOEM. The SF36 questionnaire demonstrated a significant improvement in quality of life in several domains that was sustained through 6-months' follow-up. Mean 4-hour gastric retention on gastric emptying scans decreased from 62.9% ± 24.3% to 17.6% ± 16.7% (P = .007) after GPOEM.GPOEM results in improvement in the overall symptoms of gastroparesis measured by GCSI, objective assessment of improvement in gastric emptying, and improvement in multiple domains on validated quality-of-life inventories in SF36 over a follow-up period of 6 months.

Background & Aims Gastric per oral endoscopic pyloromyotomy (GPOEM) is a promising treatment for gastroparesis. There are few data on the long-term outcomes of this procedure. We investigated long-term outcomes of GPOEM treatment of patients with refractory gastroparesis. Methods We conducted a retrospective case-series study of all patients who underwent GPOEM for refractory gastroparesis at a single center (n = 97), from June 2015 through March 2019; 90 patients had more than 3 months follow-up data and were included in our final analysis. We collected data on gastroparesis cardinal symptom index (GCSI) scores (measurements of postprandial fullness or early satiety, nausea and vomiting, and bloating) and SF-36 questionnaire scores (measures quality of life). The primary outcome was clinical response to GPOEM, defined as a decrease of at least 1 point in the average total GCSI score with more than a 25% decrease in at least 2 subscales of cardinal symptoms. Recurrence was defined as a return to baseline GCSI or GCSI scores of 3 or more for at least 2 months after an initial complete response. The secondary outcome was the factors that predict GPOEM failure (no response or gastroparesis recurrence within 6 months). Results At initial follow-up (3 to 6 months after GPOEM), 73 patients (81.1%) had a clinical response and significant increases in SF-36 questionnaire scores (indicating increased quality of life) whereas 17 patients (18.9%) had no response. Six months after GPOEM, 7.1% had recurrence. At 12 months, 8.3% of patients remaining in the study had recurrence. At 24 months, 4.8% of patients remaining in the study had a recurrence. At 36 months, 14.3% of patients remaining in the study had recurrence. For patients who experienced an initial clinical response, the rate of loss of that response per year was 12.9%. In the univariate and multivariate regression analysis, a longer duration of gastroparesis reduced the odds of response to GPOEM (odds ratio [OR], 0.092; 95% CI, 1.04–1.3; P = .001). On multivariate logistic regression, patients with high BMIs had increased odds of GPOEM failure (OR, 1.097; 95% CI, 1.022–1.176; P = .010) and patients receiving psychiatric medications had a higher risk of GPOEM failure (OR, 1.33; 95% CI, 0.110–1.008; P = .052). Conclusions In retrospective analysis of 90 patients who underwent GPOEM for refractory gastroparesis, 81.1% had a clinical response at initial follow-up of their procedure. 1 year after GPOEM, 69.1% of all patients had a clinical response and 85.2% of initial responders maintained a clinical response. Patients maintained a clinical response and improved quality of life for as long as 3 years after the procedure. High BMI and long duration gastroparesis were associated with failure of GPOEM.

Constipation is the most common GI symptom in patients with diabetes mellitus (DM). Importantly, patients with constipation have lower health-related quality of life than those without constipation. Effective therapies for constipation are limited and there is a paucity of data evaluating the treatment of constipation in diabetics.Diabetic patients with chronic idiopathic constipation (CIC) as defined by Rome III criteria were recruited from outpatient clinics at a tertiary-care center and a Veterans Administration Hospital. Demographic data, baseline stool patterns, and a constipation-specific quality of life survey (Patient Assessment of Constipation Quality of Life (PAC-QOL)) were obtained. Baseline colonic transit time (CTT) was evaluated utilizing the wireless motility capsule. Patients were randomized in a double-blind fashion to 48 mcg per day lubiprostone or placebo for 8 weeks. The primary end point measured was the difference in number of spontaneous bowel movements (SBMs) per week vs. baseline for each group at each week after initiation of therapy. Secondary end points included changes in CTT after 4 weeks of therapy, PAC-QOL after 8 weeks of therapy, and changes from baseline in associated gastrointestinal (GI) symptoms as well as need for rescue medication at 2, 4, and 8 weeks.Seventy-six patients (mean age, 56.9±9.1 years, 62% females) were randomized. There were no significant differences between the two groups' baseline data or demographics. During the 8-week treatment period, patients in the lubiprostone group experienced an average of 1.83±0.80 (P=0.02) more SBMs per week than those in the placebo group as compared with baseline. The duration of CTT at Week 4 was shorter by an average of 13 h compared with baseline in the lubiprostone group, and was prolonged by an average of 7 h compared with baseline in the placebo group, leading to a treatment effect of 20.3±7.3 h (P=0.006). PAC-QOL improved in both the groups; however, there was no significant difference between the groups. There was no difference in associated GI symptoms and need for rescue medication between the two groups after 8 weeks. There were no serious adverse events reported during the study.This study suggests that lubiprostone is a safe and effective treatment for increasing weekly SBMs and decreasing CTT in patients with DM and CIC.

Gastric per-oral endoscopic pyloromyotomy (GPOEM) is a novel procedure with promising potential for the treatment of gastroparesis but with limited data regarding predictors of clinical response. This study aims to evaluate the safety and efficacy of the procedure and explore the impact of duration and etiology (diabetic vs nondiabetic) of gastroparesis on clinical outcome as measured by the Gastroparesis Cardinal Symptom Index (GCSI).A single-center retrospective longitudinal study at a tertiary care hospital was performed over an 18-month period. Forty patients with refractory gastroparesis (25 nondiabetic and 15 diabetic patients) were included.GCSI significantly improved throughout the study period (F[2.176, 17.405] = 10.152, P = .001). The nausea/vomiting subscale showed sustained improvement through 18 months (F[2.213, 17.704] = 15.863, P .00001). There was no significant improvement in bloating (F[2.099, 16.791] = 1.576, P = .236). Gastric scintigraphy retention was significantly reduced by 41.7% (t = -7.90; P .00001). Multivariate linear regression modeling revealed a significant correlation between the duration of disease and a GCSI improvement at 12 months (P = .02), with a longer duration of disease associated with a poorer long-term response. The etiology of gastroparesis was not associated with clinical improvement (P = .16). Adverse events (7.5%) included 1 capnoperitoneum, 1 periprocedure chronic obstructive pulmonary disease exacerbation, and 1 mucosotomy closure site disruption.GPOEM appears to be a safe and effective minimally invasive therapy for refractory gastroparesis, especially for patients with predominant nausea/vomiting and shorter duration of disease, regardless of the etiology. We propose the clinical criteria for undergoing GPOEM should be a GCSI of at least 2.0 and a gastric retention of greater than 20%.

Background Gastric electrical stimulators (GESs) have been used to treat refractory gastroparesis in patients who fail initial therapies such as dietary modifications, control of psychological stressors and pharmacologic treatment. More recently, gastric peroral endoscopic pyloromyotomy (G-POEM) has emerged as a novel endoscopic technique to treat refractory gastroparesis. We present a case series of patients with refractory gastroparesis who failed treatment with an implanted GES that were safely treated with G-POEM performed under fluoroscopy as a salvage therapy. Methods Cases of G-POEM performed on patients with refractory gastroparesis who failed treatment with a GES were retrospectively reviewed. All G-POEM procedures were performed under fluoroscopic guidance with the GES still in place. Gastroparesis Cardinal Symptoms Index (GCSI) and gastric emptying scintigraphy were assessed before and after the procedure. Patients were followed up for up to 18 months post procedure. Results Five patients underwent G-POEM after failing treatment with a GES. Under fluoroscopy, the GES and their leads were visualized in different parts of the stomach. One GES lead was observed at the antrum near the myotomy site. All procedures were successfully completed without complications. Patients’ GCSI decreased by an average of 62% 1 month post procedure. Patients also had notable improvements in gastric emptying 2 months post procedure. Conclusion In patients with refractory gastroparesis who have failed treatment with a GES, G-POEM can be safe and effective without removing the GES. To visualize the GES and avoid cutting GES leads during myotomy, the procedure should be performed under fluoroscopy.

Background & Aims Gastric peroral endoscopic pyloromyotomy (GPOEM) is becoming a promising treatment option for patients with refractory gastroparesis. We aimed to systematically assess the efficacy of GPOEM and its effects on health care use. Methods We performed a retrospective study on 30 patients with refractory gastroparesis who underwent GPOEM from June 2015 through July 2017 at a tertiary center. We compared outcomes with those of 7 patients with refractory gastroparesis who did not undergo the procedure (controls). The primary outcomes were patient-reported reductions in symptoms, based on the gastroparesis cardinal symptom index (GCSI), and increases in 8 aspects of quality of life, based on Short Form 36 (SF-36) scores. Data were collected on the day of the procedure (baseline) and at 1 month, 6 months, 12 months, and 18 months afterward. Secondary outcomes included visits to the emergency department or hospitalization for gastroparesis-related symptoms. Results GPOEM was technically successful in all patients and significantly reduced GCSI scores in repeated-measure analysis of variance (F2.044, 38.838 = 22.319; P Conclusions In a retrospective study of patients who underwent GPOEM for refractory gastroparesis, we found the procedure significantly improved symptoms, increased quality of life, and reduced health care use related to gastroparesis.

Type 1 diabetes (also known as juvenile diabetes) results from the autoimmune destruction of insulin-producing pancreatic β cells, and survival of individuals with the disease depends mainly on daily insulin injections or the use of insulin pumps. Transplantation of donor islets has recently proven effective at restoring insulin production and blood glucose control in type 1 diabetes mellitus patients (1–4). Its widespread application is, however, limited by availability of donor islets, the requirement for long-term use of immunosuppressive drugs to prevent graft rejection, and lower rates of long-term insulin independence (5). Moreover, the reduced islet viability and loss of insulin content that occurs during islet isolation and pre-transplantation culture necessitates the use of large numbers of islets, usually from multiple donors, to achieve insulin independence (6). Identification of factors that can enhance islet survival in vitro and improve islet function post-transplantation will thus help in extending the period of insulin independence in type 1 diabetes patients and reduce the number of donors required for successful islet transplantation. Glial cell line-derived neurotrophic factor (GDNF) is a factor produced by glial cells that plays an important role in the development of the enteric nervous system. GDNF has previously been shown to promote the survival of β-cells in vitro, and to enhance β-cell mass and improve glucose control in mice when transgenically over-expressed under the control of the glial fibrillary acidic protein promoter (2, 7). In this study we investigated the ability of GDNF to improve human islet post-transplant survival and function. Using in vitro and in vivo methods we assessed the effects of culturing human islets in the presence of GDNF on β-cell survival, in vitro insulin secretion, and post transplantation glycemic control. We performed these studies to assess the potential for use of GDNF to enhance human islet viability before transplant in type 1 diabetes patients.

The bone morphogenetic protein (BMP) family is a class of transforming growth factor (TGF-β) superfamily molecules that have been implicated in neuronal differentiation. We studied the effects of BMP2 and glial cell line-derived neurotrophic factor (GDNF) on inducing differentiation of enteric neurons and the signal transduction pathways involved. Studies were performed using a novel murine fetal enteric neuronal cell line (IM-FEN) and primary enteric neurons. Enteric neurons were cultured in the presence of vehicle, GDNF (100 ng/ml), BMP2 (10 ng/ml), or both (GDNF + BMP2), and differentiation was assessed by neurite length, markers of neuronal differentiation (neurofilament medium polypeptide and β-III-tubulin), and neurotransmitter expression [neuropeptide Y (NPY), neuronal nitric oxide synthase (nNOS), tyrosine hydroxylase (TH), choline acetyltransferase (ChAT) and Substance P]. BMP2 increased the differentiation of enteric neurons compared with vehicle and GDNF-treated neurons ( P < 0.001). BMP2 increased the expression of the mature neuronal markers ( P < 0.05). BMP2 promoted differentiation of NPY-, nNOS-, and TH-expressing neurons ( P < 0.001) but had no effect on the expression of cholinergic neurons (ChAT, Substance P). Neurons cultured in the presence of BMP2 have higher numbers of TH-expressing neurons after exposure to 1-methyl 4-phenylpyridinium (MPP+) compared with those cultured with MPP+alone ( P < 0.01). The Smad signal transduction pathway has been implicated in TGF-β signaling. BMP2 induced phosphorylation of Smad1, and the effects of BMP2 on differentiation of enteric neurons were significantly reduced in the presence of Smad1 siRNA, implicating the role of Smad1 in BMP2-induced differentiation. The effects of BMP2 on catecholaminergic neurons may have therapeutic implications in gastrointestinal motility disturbances.

Chronic Granulomatous Disease (CGD) represents a group of inherited disorders of phagocytic system, manifesting recurrent infections at different sites. The present study was accomplished in order to determine the gastrointestinal manifestations of CGD patients. Fifty-seven patients (38 males and 19 females) with CGD, who had been referred to three immunodeficiency referral centers in Iran, were studied during a 24-year period (1980-2004). The median age at the time of study was 14.5 years old (1-56 years). The median onset age of symptoms was 5 months (1 month- 13.75 years), and that of diagnostic age was 5 years (2 months- 54.1 years), with a diagnostic delay of 33 months, on average. Seven patients were presented with acute diarrhea, 3 with oral candidiasis, and 2 with liver abscesses as the first chief complaints. Twenty-four cases (42.1%) had been complicated by gastrointestinal manifestations during their course of the disease. Of those, 12 cases (21.1%) had diarrhea, 7 (12.3%) oral candidiasis, 5 (8.8%) hepatitis, 4 (7.0%) hepatic abscess, and 2 cases (3.5%) gastric outlet obstruction. Also, failure to thrive was detected in 6 patients (10.5%). Four patients died (7%). CGD should be excluded in any patient with gastrointestinal manifestations especially chronic diarrhea, hepatic abscess, and gastric outlet obstruction.

Background: Chronic granulomatous disease (CGD) represents a group of inherited disorders of the phagocytic system, involving recurrent infections at different sites, especially the respiratory system. The present study was accomplished in order to determine the clinical spectrum of Iranian patients with CGD. Methods: Forty-one patients (29 males and 12 females) with CGD, who had already been referred to two immunodeficiency referral centers in Iran, were reviewed during a 22-year period (1980–2002). Results: These patients belonged to 34 families, and 56% of them were consanguineous. The median age at the time of study was 12 years (3 months to 22 years). The median age at onset of symptoms was 4 months (1 month to 12 years), and the median diagnostic age was 5.5 years (2 months to 20 years), with a diagnostic delay of 3 years on average. The most common presenting complaint in our CGD patients was lymphadenopathy (seen in 11 patients, 26.8%). The most common manifestations of CGD (in descending order) were lymphadenopathy (75.6%), pulmonary infections (65.9%) and skin involvement (63.4%) during their illness, followed by gastrointestinal (56.1%), skeletal (29.3%), upper respiratory tract (26.8%) and central nervous system (2.4%) involvement. Conclusions: Early diagnosis of the disease is crucial. In view of the possibility of timely treatment, i.e. prophylactic treatment of infection, CGD should be excluded in any patient with unexplained infections or granulomas.

by Los Angeles (LA) classification were evaluated. Results: Seventy patients (48%) were partial responder to PPI therapy. These patients reported significantly lower scores in the mental health component summary of SF-8, PSQI and HADS including anxiety and depression than responder to PPI. Anxious or depressive state patients (HADS total score>11) are 69% in partial responder to PPI, whereas 31% in responder to PPI (P=0.006). PPI daily dose and LA classification were also significant factors that associated with the response to PPI. Conclusion: Partial responder to PPI showed decreased mental HRQoL. Persistent and troublesome reflux symptoms on PPI therapy seemed to be important factors affecting mental HRQoL including anxiety, depression and sleep disturbance in Japanese GERD patients. The scores of each questionnaire

Background Gastrointestinal dysfunction is very common in diabetic patients. We assessed the changes in the colonic enteric nervous system using colectomy specimens and intestinal biopsies from diabetic subjects and age-matched controls. Methods In control and diabetic colons, we determined the total ganglion area (hematoxylin–eosin staining), changes in neuronal markers–protein gene product 9.5, peripherin, neuronal nitric oxide synthase (nNOS), neuropeptide Y (NPY), choline acetyl transferase (ChAT) and vasoactive intestinal peptide (by immunostaining), apoptosis (cleaved caspase-3 staining) and reduced glutathione levels. Superoxide dismutase mRNA was determined in enteric ganglia isolated by laser capture micro dissection. Isometric muscle recording was used to assess contraction and relaxation responses of colonic circular muscle strips. Apoptosis in enteric neurons under hyperglycemia in vitro was determined by cleaved caspase-3 Western blotting and protective effects of lipoic acid were evaluated. Key Results Diabetic subjects had higher incidence of lower gastrointestinal symptoms like constipation and diarrhea at baseline prior to surgery. Diabetic ganglia displayed significant decrease in ganglion size due to enhanced apoptosis and loss of peripherin, nNOS, NPY, and ChAT neurons. Reduced glutathione levels in the diabetic colon (HbA1C > 7%) were significantly less than the control, indicating increased oxidative stress. Colonic circular muscle strips from diabetic subjects showed impaired contraction and relaxation responses compared with the healthy controls. Hyperglycemia-induced cleaved caspase-3 in enteric neurons was reversed by lipoic acid. Conclusions & Inferences Our data demonstrate loss of enteric neurons in the colon due to increased oxidative stress and apoptosis which may cause the motility disturbances seen in human diabetes. Antioxidants may be of therapeutic value for preventing motility disorders in diabetes.