Successful Endoscopic Submucosal Dissection Using Open Peroral Endoscopic Myotomy for Duodenal Neuroendocrine Tumor.

Duodenal neuroendocrine tumors (NETs) are subepithelial tumors that are difficult to remove endoscopically, particularly when located just beyond the pylorus. This paper reports a case of a successful endoscopic submucosal dissection (ESD) using open gastric peroral endoscopic myotomy (POEM) for a remnant duodenal NET detected after endoscopic mucosal resection (EMR). A 67-year-old male presented with a 5 mm remnant duodenal NET close to the pylorus after EMR for a duodenal polypoid lesion performed four months earlier. Duodenal ESD was performed under conscious sedation using I-type and IT II knives. The tumor adhered to the fibrotic tissue, and the submucosal cushion was insufficient. Open gastric POEM was performed concurrently during ESD, resulting in the complete resection of the NET. This case suggests that while challenging, open gastric POEM can serve as a valuable technique for endoscopic resection in cases of early gastric cancer or duodenal masses located around the pylorus.

A cross-sectional study reveals a chronic low-grade inflammation in achalasia.

BACKGROUND AND AIM: Immune-mediated neuroinflammation has been proposed to underlie the loss of lower esophageal sphincter (LES) myenteric neurons in achalasia. However, the immune status and key pathogenic immune subpopulations remain unclear. This study aims to evaluate the inflammatory status of patients with achalasia and their correlation with clinical characteristics, and further explore the key pathogenic subpopulations. METHODS: We investigated the complete blood cell count and inflammatory markers in a large population of patients with achalasia (n = 341) and healthy controls (n = 80). The subpopulations of lymphocytes were analyzed by flow cytometry. Immunofluorescence was used to determine immune cell infiltration in the LES. Transcriptome changes of the key subpopulation were determined by RNA sequencing analysis. RESULTS: NLR, MLR, CRP, globulin, IL-6 and IL-10 were significantly elevated in patients with achalasia. MLR and globulin were positively correlated with disease duration. The absolute count and percentage of CD8+ T cells in peripheral blood and its infiltration around ganglion in the LES were significantly increased in achalasia. Transcriptome analysis indicated that CD8+ T cells were activated and proliferative. In addition to multiple inflammatory pathways, regulation of neuroinflammatory response pathway was also significantly up-regulated in achalasia. GSEA analysis revealed a close association with autoimmune diseases. CONCLUSIONS: Patients with achalasia suffered from chronic low-grade inflammation with dysregulated immune cells and mediators associated with disease duration. CD8+ T cells might be the key pathogenic subpopulation of achalasia. Our results provide an important immune cell signature of the pathogenesis of achalasia.

Effect of esophageal muscle fibrosis on prognosis of per-oral endoscopic myotomy (POEM) in achalasia patients.

BACKGROUND AND AIMS: Although esophageal smooth muscle fibrosis of achalasia (AC) patients has been described, the role and mechanism remain unclear. The aim of this study was to evaluate the fibrosis in the distal esophageal muscle in patients with AC and explore its relationship with prognosis of per-oral endoscopic myotomy (POEM). METHODS: Lower esophageal sphincter (LES) muscle from forty patients undergoing POEM for AC were obtained at the time of surgery. Control specimens consisted of similar muscle taken from distal esophagectomy for gastric tumors. The muscle fibrosis were assessed by Masson staining and confirmed by immunohistochemistry for collagen I and III. The total number of eosinophil within the myenteric propria were counted. In addition, clinical data were obtained through electronic medical records. Statistical comparison between groups were made. RESULTS: A significantly higher proportion of fibrosis in AC as compared with controls (P = 0.000). Eosinophil count, TGF-ß1, collagen I, and III were higher than those of control (P = 0.000, P = 0.001, P = 0.011, and P = 0.002, respectively). TGF-ß1, collagen I, and III were positively correlated with eosinophil count (all P < 0.05). Furthermore, the proportion of severe LES fibrosis in patients who failed to respond to POEM two years after operation was higher than that in responders (P = 0.028). And, Eckardt score two years after POEM was also positively correlated with degree of fibrosis-related cytokines (all P < 0.05). CONCLUSION: Smooth muscle fibrosis was prominent in lower part of esophagus of AC and positively correlated with severity of symptoms two years after POEM. The fibrosis might be relevant to eosinophil infiltration and TGF-ß1. Further studies are required to more clearly delineate the mechanism of muscle fibrosis and its correlation with prognosis of therapy for this idiopathic disease.

The Number of Interstitial Cells of Cajal Differs Among Different Subtypes of Achalasia and is Related to Patients' Prognosis.

INTRODUCTION: Achalasia is a primary esophageal motility disorder with heterogeneous manometric subtypes and prognosis, characterized by degeneration of the esophageal myenteric plexus, and reduction in interstitial cells of Cajal (ICCs). This study aimed to explore the histopathologic characteristics of lower esophageal sphincter (LES) muscle from patients with achalasia with different subtypes and different prognosis. METHODS: We examined specimens of LES muscle from 122 patients with achalasia who underwent peroral endoscopic myotomy and from 10 control patients who underwent esophagectomy for esophageal cancer. Hematoxylin-eosin staining was performed to assess inflammation infiltration, fibrosis, and atrophy. Specific immunohistochemical staining was performed to identify ICCs and neuronal nitric oxide synthase (nNOS). RESULTS: The number of ICCs in patients with type I achalasia was significantly lower than that in patients with type II achalasia, followed by that in control patients (type I vs type II vs control group= 0.4 vs 1.2 vs 9.5; P < 0.001). The number of nNOS-positive cells was significantly lower in patients with achalasia than that in control patients (type I vs type II vs control group = 0.0 vs 0.0 vs 8.0; P < 0.001). Nonrecurrent group had significantly more ICCs than recurrent group (type I: nonrecurrent vs recurrent = 1.0 vs 0.1; P = 0.010; type II: nonrecurrent vs recurrent = 2.0 vs 0.4; P = 0.004). DISCUSSION: ICCs and nNOS-positive cells reduced significantly in LES muscle of patients with achalasia. The number of ICCs differed among different achalasia subtypes and was related to patients' clinical prognosis.

Pressure and length of the lower esophageal sphincter as predictive indicators of therapeutic efficacy of baclofen for refractory gastroesophageal reflux-induced chronic cough.

BACKGROUND: Therapeutic efficacy of baclofen is suboptimal in the treatment of refractory gastroesophageal reflux-induced chronic cough (GERC). The purpose of the study is to identify its therapeutic predictors in a prospective clinical study. METHODS: 138 patients with suspected refractory GERC were treated with baclofen. Before the therapy, all the patients underwent esophageal manometry and multichannel intraluminal impedance-pH monitoring to establish the diagnosis. After the efficacy of baclofen was evaluated, a stepwise logistic regression analysis was performed to identify the therapeutic predictors of baclofen and to establish a regression prediction model. RESULTS: The overall response rate of baclofen treatment was 52.2% (72/138). The lower esophageal sphincter pressure (LESP) (odds ratio (OR) = 0.592, P = 0.000) and lower esophageal sphincter length (LESL) (OR = 0.144, P = 0.008) were independent predictors of baclofen efficacy. The optimal cut-off point to predict baclofen efficacy for LESP was 11.00 mmHg, with a sensitivity of 83.7% and specificity of 79.1% while that for LESL was 2.35 cm, with a sensitivity of 81.6% and specificity of 72.1%. The highest predictive specificity (90.7%) was achieved when both LESP and LESL were jointly used. CONCLUSIONS: LESP and LESL may be used to screen the patients with refractory GERC suitable for baclofen therapy and help improve the therapeutic precision. CLINICAL TRIAL REGISTRATION: ChiCTR- ONC-13003123.

Achalasia is associated with a higher incidence of depression in outpatients in Germany.

BACKGROUND AND AIM: Achalasia represents a chronic motility disorder of the esophagus featuring an impaired lower esophageal sphincter relaxation and loss of esophageal peristalsis. By causing dysphagia, regurgitation, aspiration and chest pain, achalasia might tremendously affect life quality of patients. However, the impact of achalasia on the development of mood disorders including depression has largely remained unclear. The aim of this study was to evaluate the incidence of depression in achalasia patients. METHODS: We analyzed a large primary care cohort database in Germany capturing data from 7.49 million patients. RESULTS: A total of n = 1,057 patients with achalasia diagnosed between January 2005 and December 2018 were matched to a cohort of n = 3,171 patients without achalasia controlling for age, sex, physician, index year, and the Charlson comorbidity index. Interestingly, while the frequency of depression prior to the diagnosis of achalasia was comparable in both groups, new diagnoses of depression were significantly higher within one year after the diagnosis of achalasia compared to the control group, suggesting a direct and previously unrecognized association between achalasia and depression. CONCLUSION: Our data suggest that the clinical management of patients with achalasia should include a careful and structured work-up for mood disorders in order to improve long-term quality of life in these patients.

Physiological and pathological roles of the accommodation response in lower esophageal sphincter relaxation during wet swallows.

The preparatory accommodation response of lower esophageal sphincter (LES) before swallowing is one of the mechanisms involved in LES relaxation during wet swallows, however, the physiological and/or pathological roles of LES accommodation remain to be determined in humans. To address this problem, we conducted a prospective observational study of 38 patients with normal high-resolution manometry (HRM) and 23 patients with idiopathic esophagogastric junction outflow obstruction (EGJOO) to assess dry and wet swallows. The LES accommodation measurement was proposed for practical use in evaluating the LES accommodation response. Although swallow-induced LES relaxation was observed in both dry and wet swallows, LES accommodation (6.4, 3.1-11.1 mmHg) was only observed in wet swallows. The extent of LES accommodation was impaired in idiopathic EGJOO (0.6, - 0.6-6 mmHg), and the LES accommodation measurement of patients with idiopathic EGJOO (36.8, 29.5-44.3 mmHg) was significantly higher in comparison to those with normal HRM (23.8, 18-28.6 mmHg). Successful LES relaxation in wet swallowing can be achieved by LES accommodation in combination with swallow-induced LES relaxation. Impaired LES accommodation is characteristic of idiopathic EGJOO. In addition to the IRP value, the LES accommodation measurement may be useful for evaluating the LES relaxation function in clinical practice.

Lower esophageal sphincter muscle of patients with achalasia exhibits profound mast cell degranulation.

BACKGROUND: Eosinophils and mast cells are key effectors of allergy. When they accumulate in the esophagus, their myoactive, pro-inflammatory, and cytotoxic products potentially could cause achalasia-like motility abnormalities and neuronal degeneration. We hypothesized that there is an allergy-mediated form of achalasia. METHODS: LES muscle samples obtained during Heller myotomy from patients with achalasia or EGJ outflow obstruction (EGJOO) and from organ donor controls were immunostained for tryptase. Eosinophil and mast cell density, and mast cell degranulation were assessed. LES muscle was evaluated by qPCR for genes mediating smooth muscle Ca2+ handling and contraction. KEY RESULTS: There were 13 patients (7 men, median age 59; 10 achalasia, 3 EGJOO) and 7 controls (4 men, median age 42). Eosinophils were infrequent in LES muscle, but mast cells were plentiful. Patients and controls did not differ significantly in LES mast cell density. However, 12 of 13 patients exhibited profound LES mast cell degranulation involving perimysium and myenteric plexus nerves, while only mild degranulation was seen in 2 of 7 controls. Hierarchical clustering analysis of qPCR data revealed two "mototype" LES gene expression patterns, with all type II patients in one mototype, and type I and III patients in the other. CONCLUSIONS & INFERENCES: LES muscle of patients with achalasia or EGJOO exhibits striking mast cell degranulation, and patients with different achalasia manometric phenotypes exhibit different LES patterns of expression for genes mediating Ca2+ handling and muscle contraction. Although these findings are not definitive, they support our hypothesis that achalasia can be allergy-driven.

Do we understand the pathophysiology of GERD after sleeve gastrectomy?

Gastroesophageal reflux disease (GERD), a prevalent problem among obese individuals, is strongly associated with obesity and weight loss. Hence, bariatric surgery effectively improves GERD for many patients. Depending on the type of bariatric procedure, however, surgery can also worsen or even cause a new onset of GERD. As a consequence, GERD remains a relevant problem for many bariatric patients, and especially those who have undergone sleeve gastrectomy (SG). Affected patients report not only a decrease in physical functioning but also suffer from mental and emotional problems, resulting in poorer social functioning. The pathomechanism of GERD after SG is most likely multifactorial and triggered by the interaction of anatomical, physiological, and physical factors. Contributing factors include the shape of the sleeve, the extent of injury to the lower esophageal sphincter, and the presence of hiatal hernia. In order to successfully treat post-sleeve gastrectomy GERD, the cause of the problem must first be identified. Therapeutic approaches include lifestyle changes, medication, interventional treatment, and/or revisional surgery.

The Benefits of Nonablative Radiofrequency Treatment of the Lower Esophageal Sphincter After Transoral Incisionless Fundoplication.

Non-ablative radiofrequency treatment to the lower esophageal sphincter (Stretta) has been shown to be beneficial after failed Nissen fundoplication. To our knowledge, this is the first report of Stretta after transoral incisionless fundoplication (TIF). This patient is a 17-year-old female who had gastroesophageal reflux disease (GERD) symptoms for 9 years. She presented with heartburn, regurgitation, and epigastric discomfort. She used omeprazole for 9 years. Esophagogastroduodenoscopy (EGD) showed a 2 cm sliding hiatal hernia and DeMeester score of 25. The GERD Health-Related Quality of Life (GERD-HRQL) score on omeprazole was 14. Patient underwent a TIF procedure, which was uneventful. Her symptoms resolved, and she discontinued omeprazole. Six months later, she had episodes of repeated violent vomiting followed by recurrence of regurgitation, nausea, bloating, and dysphagia. She resumed omeprazole. Diagnostic workup included gastric emptying scan, which was normal. EGD showed no hiatal hernia and partial disruption of the TIF valve. DeMeester score was 36.3. Esophageal manometry with impedance showed intact peristalsis and normal relaxation of the lower esophageal sphincter. The patient underwent Stretta, which was uneventful. The previous TIF did not increase the complexity of the procedure. There were no immediate or postoperative complications. The patient reported gradual improvement of her symptoms with complete resolution 2 months postoperatively. She discontinued omeprazole. The GERD-HRQL score 17 months post-Stretta was 0. This case highlights the feasibility, safety, and efficacy of performing Stretta following TIF. It provides an endoluminal alternative to complex revisional antireflux surgery. Prospective studies with longer follow-up are required to validate this concept.

European guidelines on achalasia: United European Gastroenterology and European Society of Neurogastroenterology and Motility recommendations.

INTRODUCTION: Achalasia is a primary motor disorder of the oesophagus characterised by absence of peristalsis and insufficient lower oesophageal sphincter relaxation. With new advances and developments in achalasia management, there is an increasing demand for comprehensive evidence-based guidelines to assist clinicians in achalasia patient care. METHODS: Guidelines were established by a working group of representatives from United European Gastroenterology, European Society of Neurogastroenterology and Motility, European Society of Gastrointestinal and Abdominal Radiology and the European Association of Endoscopic Surgery in accordance with the Appraisal of Guidelines for Research and Evaluation II instrument. A systematic review of the literature was performed, and the certainty of the evidence was assessed using the Grading of Recommendations Assessment, Development and Evaluation methodology. Recommendations were voted upon using a nominal group technique. RESULTS: These guidelines focus on the definition of achalasia, treatment aims, diagnostic tests, medical, endoscopic and surgical therapy, management of treatment failure, follow-up and oesophageal cancer risk. CONCLUSION: These multidisciplinary guidelines provide a comprehensive evidence-based framework with recommendations on the diagnosis, treatment and follow-up of adult achalasia patients.

Esophageal manometry in systemic sclerosis: findings and association with clinical manifestations.

INTRODUCTION: Systemic sclerosis (SSC) is an autoimmune disorder that affects several organs of unknown etiology, characterized by vascular damage and fibrosis of the skin and organs. Among the organs involved are the esophagus and the lung. OBJECTIVES: To relate the profile of changes in esophageal electromanometry (EM), the profile of skin involvement, interstitial pneumopathy (ILD), and esophageal symptoms in SSC patients. METHODS: This is an observational, cross-sectional study carried out at the SSC outpatient clinic of the Hospital de Clínicas of the Federal University of Uberlândia. After approval by the Ethics Committee and signed the terms of consent, 50 patients were initially enrolled, from 04/12/2014 to 06/25/2015. They were submitted to the usual investigations according to the clinical picture. The statistical analysis was descriptive in percentage, means, and standard deviation. The Chi-square test was used to evaluate the relationship between EM, high-resolution tomography, and esophageal symptoms. RESULTS: 91.9% of the patients had some manometric alterations. 37.8% had involvement of the esophageal body and lower esophageal sphincter. 37.8% had ILD. 24.3% presented the diffuse form of SSC. No association was found between manometric changes and clinical manifestations (cutaneous, pulmonary, and gastrointestinal symptoms). CONCLUSION: The present study confirms that esophageal motility alterations detected by EM are frequent in SSC patients, but may not be related to cutaneous extension involvement, the presence of ILD, or the gastrointestinal complaints of patients.

Triosephosphate isomerase, carbonic anhydrase, and creatinine kinase-brain isoform are possible antigen targets in patients with achalasia.

BACKGROUND: Idiopathic achalasia is an uncommon esophageal motor disorder. The disease involves interaction between inflammatory and autoimmune responses. However, the antigens related to the disease are still unknown. AIM: To identify the possible antigen targets in muscle biopsies from lower esophageal sphincter (LES) of achalasia patients. METHODS: Esophageal biopsies of patients with type I and type II achalasia and esophagogastric junction outflow obstruction (EGJOO) were analyzed. Lower esophageal sphincter muscle biopsy from a Healthy organ Donor (HD) was included as control for two-dimensional gel electrophoresis. Immunoblotting of muscle from LES lysate with sera of type I, type II achalasia, or type III achalasia, sera of EGJOO and sera of healthy subjects (HS) was performed. The target proteins of the serum were identified by mass spectrometry Matrix-assited laser desorption/ionization time-of-flight (MALDI-TOF). KEY RESULTS: The proteomic map of muscle from LES tissue lysates of type I, and type II achalasia, EGJOO, and HD were analyzed and divided into three important regions. We found a difference in the concentration of certain spots. Further, we observed the serum reactivity of type I achalasia and type II achalasia against 45 and 25 kDa bands of type I achalasia tissue. Serum of type III achalasia and EGJOO mainly recognized 25 kDa band. Bands correspond to triosephosphate isomerase (TPI) (25 kDa), carbonic anhydrase (CA) (25 kDa) and creatinine kinase-brain (CKB) isoform (45 kDa). CONCLUSIONS AND INFERENCES: We identify three antigen targets, TPI, CA, and CKB isoform, which are recognized by sera from patients with achalasia.

Esophageal manometry in systemic sclerosis: findings and association with clinical manifestations

SUMMARY INTRODUCTION Systemic sclerosis (SSC) is an autoimmune disorder that affects several organs of unknown etiology, characterized by vascular damage and fibrosis of the skin and organs. Among the organs involved are the esophagus and the lung. OBJECTIVES To relate the profile of changes in esophageal electromanometry (EM), the profile of skin involvement, interstitial pneumopathy (ILD), and esophageal symptoms in SSC patients. METHODS This is an observational, cross-sectional study carried out at the SSC outpatient clinic of the Hospital de Clínicas of the Federal University of Uberlândia. After approval by the Ethics Committee and signed the terms of consent, 50 patients were initially enrolled, from 04/12/2014 to 06/25/2015. They were submitted to the usual investigations according to the clinical picture. The statistical analysis was descriptive in percentage, means, and standard deviation. The Chi-square test was used to evaluate the relationship between EM, high-resolution tomography, and esophageal symptoms. RESULTS 91.9% of the patients had some manometric alterations. 37.8% had involvement of the esophageal body and lower esophageal sphincter. 37.8% had ILD. 24.3% presented the diffuse form of SSC. No association was found between manometric changes and clinical manifestations (cutaneous, pulmonary, and gastrointestinal symptoms). CONCLUSION The present study confirms that esophageal motility alterations detected by EM are frequent in SSC patients, but may not be related to cutaneous extension involvement, the presence of ILD, or the gastrointestinal complaints of patients.

RESUMO INTRODUÇÃO A esclerose sistêmica (ES) é uma doença autoimune que afeta vários órgãos de etiologia desconhecida, caracterizada por dano vascular e fibrose da pele e órgãos. Entre os órgãos envolvidos estão o esôfago e o pulmão. OBJETIVOS Relacionar o perfil das alterações na eletromanometria (ME), o perfil de acometimento da pele, a pneumopatia intersticial (PI) e os sintomas esofágicos em pacientes com ES. MÉTODO Trata-se de um estudo observacional, transversal, realizado no ambulatório de SSC do Hospital das Clínicas da Universidade Federal de Uberlândia. Após aprovação pelo Comitê de Ética e assinatura dos termos de consentimento, 50 pacientes foram inicialmente convidados, de 04/12/2014 a 25/06/2015. Eles foram submetidos às investigações usuais de acordo com o quadro clínico. A análise estatística foi descritiva em porcentagem, média e desvio padrão. O teste Qui-quadrado foi utilizado para avaliar a relação entre ME, tomografia de alta resolução e sintomas esofágicos. RESULTADOS 91,9% dos pacientes apresentaram alterações manométricas. 37,8% tinham envolvimento do corpo esofágico e do esfíncter esofágico inferior. 37,8% tinham IP. 24,3% apresentaram a forma difusa da ES. Não há associação entre alterações manométricas e manifestações clínicas (sintomas cutâneos, pulmonares e gastrointestinais). CONCLUSÃO O presente estudo confirma que as alterações da motilidade esofágica detectadas pela EM são frequentes em pacientes com SSC, mas podem não estar relacionadas ao envolvimento cutâneo, à de DPI ou às queixas gastrointestinais dos pacientes.

High-resolution Manometry can Characterize Esophagogastric Junction Morphology and Predict Esophageal Reflux Burden.

BACKGROUND: High-resolution manometry (HRM) allows characterization of esophagogastric junction (EGJ) morphology and identification of hiatus hernia using novel software tools. AIM: The main purpose of this study was to determine the impact of HRM-based EGJ and lower esophageal sphincter (LES) metrics in predicting abnormal reflux burden. METHODS: Total, upright, and supine acid exposure times (AETs) were extracted from ambulatory reflux monitoring performed off therapy in 482 patients (54.2±0.6 y, 63.3% female patients). EGJ morphology was categorized into type 1 (superimposed LES and crural diaphragm), type 2 (<3 cm separation between LES and crural diaphragm), and type 3 (≥3 cm separation). EGJ-contractile integral (EGJ-CI) and distal contractile integral (DCI) were extracted. Conventional EGJ and LES metrics, including basal and end-expiratory LES pressure, and LES length were also analyzed. Univariate and multivariate analyses were performed to determine the value of HRM parameters in predicting abnormal esophageal reflux burden. RESULTS: Type 1 EGJ was noted in 298 (61.8%), type 2 in 125 (25.9%), and type 3 in 59 (12.2%); EGJ-CI and mean DCI were lower with abnormal EGJ morphology. Mean AET, and proportions with abnormal AET increased as EGJ morphology became progressively disrupted (P<0.0001 across groups); low EGJ-CI was additive in predicting abnormal AET. All HRM parameters assessed (EGJ morphology, EGJ-CI, and DCI) were independent predictors for abnormal AET (P≤0.02). Conventional LES and EGJ metrics were also associated with abnormal reflux burden, but intra-abdominal LES length, and hiatus hernia size did not independently predict total AET. CONCLUSIONS: HRM-based EGJ morphology and EGJ barrier assessment independently predict esophageal reflux burden.

The relationship between gastroesophageal junction integrity and symptomatic fundoplication outcomes.

BACKGROUND: The majority of patients who undergo a laparoscopic fundoplication for gastroesophageal reflux disease (GERD) have a structural (hiatal hernia, shortened lower esophageal sphincter [LES]) or functional (weak LES) defect of the gastroesophageal junction (GEJ). We hypothesized that the symptomatic outcomes of fundoplication in patients with a competent GEJ prior to surgery are inferior to those with an incompetent GEJ. METHODS: This is a retrospective review of prospectively maintained data on subjects who underwent primary laparoscopic fundoplication (Nissen or Toupet) for medically refractory and confirmed GERD. Three esophageal manometry variables were used to determine GEJ competency: (1) hiatal hernia (normal = no hernia), (2) total lower esophageal sphincter length (normal ≥ 2.43 cm), and (3) lower esophageal sphincter pressure (normal = 15.0-43.7 mmHg). Patients in the competent group had normal values for all 3 variables. Symptomatic outcomes were assessed with the GERD Health-Related Quality of Life (HRQL) survey administered pre- and postoperatively, and then compared both intragroup, intergroup, and by procedure. RESULTS: A total of 78 patients met inclusion criteria-17 competent GEJ and 61 incompetent GEJ patients. GERD-HRQL scores improved in the incompetent cohort at all intervals out to 2 years postoperatively. GERD-HRQL improved in the competent cohort at 2 months, with no difference at 6 months or 2 years postoperatively compared to preoperative scores. Competent GEJ patients receiving a Nissen fundoplication had a higher rate of additional procedures (endoscopy with or without dilation, pH studies) following surgery to address recurrent or persistent GERD symptoms compared to Toupet. CONCLUSIONS: GERD patients with a competent GEJ report a lower GERD-HRQL with more frequent and severe reflux symptoms up to 2 years post-fundoplication. Competent GEJ patients receiving a Nissen fundoplication are more likely to have additional procedures to address symptoms following surgery. Surgeons should approach patients with a competent GEJ and medically refractory GERD with caution.

Identification of human herpes virus 1 encoded microRNAs in biopsy samples of lower esophageal sphincter muscle during peroral endoscopic myotomy for esophageal achalasia.

Esophageal achalasia is a rare chronic debilitating disorder characterized by incomplete lower esophageal sphincter (LES) relaxation and abnormal peristalsis as a result of myenteric plexus degeneration. Although complex interactions among immunity, viruses and inheritance have been proposed, its causes remain unknown. MicroRNAs (miRs) play crucial roles in the regulation of gene expression during pathophysiological processes. Certain viruses such as herpes simplex virus (HSV) encode miRs derived from their own genomes. To determine the underlying relationship of miRNAs to achalasia, we analyzed the expression profile of miRNAs using biopsy samples obtained from LES muscle during peroral endoscopic myotomy. Peroral LES muscle biopsy sampling was uneventfully carried out in our case series of achalasia. Control biopsy tissues were also obtained from LES muscle of patients without symptoms relating to abnormal esophageal motility whose esophagogastric junction was surgically excised. RNA was extracted from biopsy specimens and analyzed using a microarray. Differentially expressed miRNAs in achalasia patients compared to controls were identified and analyzed using reverse transcription quantitative polymerase chain reaction. HSV-1-derived hsv1-miR-H1 and -H18 was significantly overexpressed in achalasia cohorts compared to controls. Correlations between the expression levels of viral miR and the patients' clinical characteristics including achalasia morphological type, dilatation grading, and disease duration were not identified. Further studies with a larger sample size are needed to replicate the current heuristic identification of neurotropic viral miRs and unravel their functional significance in order to provide new insight linking neurodegenerative etiology in achalasia.

Per-oral endoscopic myotomy (POEM) for a sigmoid type of achalasia: short-term outcomes and changes in the esophageal angle.

BACKGROUND: Per-oral endoscopic myotomy (POEM) is an endoscopic procedure whereby the esophageal muscle is incised in order to lower the lower esophageal sphincter (LES) pressure. Since the time it was first performed in 2008 and subsequently reported on in 2010 by Inoue et al., POEM has been shown to be safe and effective for straight type of achalasia. On the other hand, the efficacy of POEM had been controversial for patients with achalasia of the sigmoid type, in which a high LES pressure is accompanied by morphological changes, including dilation, acute angulation, and rotation. The aim of this study is to evaluate the safety and efficacy of POEM in patients with sigmoid type of achalasia. METHODS: Between May 2015 and December 2017, 16 patients with a sigmoid type of achalasia underwent POEM in our institute. The POEM procedure was the same as that for the straight type of achalasia. The double-scope technique was used to check the distal end of the submucosal tunnel from the gastric side. The primary endpoint was improvement of Eckardt score at 2 months after POEM. The secondary endpoints comprised operating time, change in the esophageal angulation, and adverse events. RESULTS: All patients underwent POEM without severe adverse events. The respective parameters before and after POEM significantly differed in terms of mean (SD) Eckardt score [4.9 (2.0) vs. 0.4 (0.6), p < 0.01], LES pressure [19.4 (10.2) vs. 9.2 (6.4), p < 0.01], and integrated relaxation pressure [17.6 (9.2) vs. 7.9 (5.5), p < 0.01]. The average operation time was 94.7 ± 31.4 min. The average esophageal angulation was 88.4° ± 23.1° before POEM and 109.5° ± 16.7° after POEM (p < 0.01). Four patients had postoperative complications that were treated conservatively. CONCLUSIONS: POEM can improve both LES pressure and esophageal angulation in patients with sigmoid achalasia.

Peroral Endoscopic Myotomy Is Feasible and Safe in a Gastric Bypass Population.

BACKGROUND: Obesity is public health problem of epidemic proportions. Esophageal dysmotility including achalasia is more commonly seen in an obese population. Standard therapy for achalasia can be complicated by hepatomegaly and a post-surgical anatomy in a pre- and post-bariatric population. Peroral endoscopic myotomy (POEM) has not been adequately studied in this population. METHODS: A retrospective review of a prospectively collected database was completed. Patients who had undergone a Roux-en-y gastric bypass (RYGB) prior to or following a POEM were enrolled. Patient demographics, operative information and post-operative course data was collected. RESULTS: Six patients underwent POEM prior to or after RYGB. There were no peri-operative complications with an average length of stay of 1.2 days. Five patients experienced a clinical success with excellent symptom resolution. The one failure was in the setting of type III achalasia, but did have objective evidence of lower esophageal sphincter (LES) relaxation post-operatively. CONCLUSION: POEM in the setting of bariatric surgery is safe and feasible. The potential increase in GERD following POEM is obviated by RYGB anatomy. In an obese individual, a staged POEM prior to or following a RYGB is an appropriate treatment algorithm for obese and achalasia.

Mast cell infiltration associated with loss of interstitial cells of Cajal and neuronal degeneration in achalasia.

BACKGROUND: Achalasia is a motility disorder of unknown etiology. Previous studies supported the hypothesis that autoimmune-mediated inflammatory responses produce inhibitory neuronal degeneration. This study was designed to explore the role of mast cells in achalasia. METHODS: We collected information from 116 patients with achalasia who underwent peroral endoscopic myotomy between December 2016 and May 2017. Lower esophageal sphincter (LES) muscle biopsy was performed in all patients with achalasia, as well as 20 control subjects. The number of mast cells, interstitial cells of Cajal (ICCs), nNOS-positive cells, and S-100-positive cells in the LES were evaluated by immunohistochemistry. Pathological and clinical data were compared between groups. KEY RESULTS: Compared with controls, the LES of patients with achalasia had significantly fewer ICCs, nNOS-positive cells, and S-100-positive cells and a higher number of mast cells (all P < 0.001). Furthermore, the increased mast cell infiltration was significantly associated with decreased ICCs, nNOS-positive cells, and S-100-positive cells in patients with achalasia (all P < 0.05). Clinically, the number of strongly positive mast cells was highest in patients with type I achalasia and lowest in those with type III achalasia (P < 0.001). In addition, patients with a history of autoimmune disease or viral infection had greater mast cell infiltration in the LES muscle (P = 0.040). CONCLUSIONS & INFERENCES: In patients with achalasia, mast cell infiltration in the LES muscle is increased, in association with loss of ICCs and neuronal degeneration. Mast cells may thereby play a crucial role in the development of achalasia.