Hybrid Laparo-Endoscopic Resection of Submucosal Cardial Tumors Assisted by Flexible Articulated Instruments.

We report a new surgical method in 10 patients who underwent hybrid laparo-endoscopic resection (HLER) of submucosal tumors with the combination of flexible articulated laparoscopic instruments (FALI). We have assessed technical reproducibility, safety, and morbidity. Resection was completed in all cases. Mean surgical time was 60 min (30-85). Median tumor size was 16 mm (12-30). The more frequent location was the gastroesophageal junction. No complications were observed during the procedure. Length of stay was 1 day in all cases. We have found HLER to be a safe procedure allowing margin resection and organ preservation. The addition of FALI added ease of performance in hard-to-reach tumor locations.

Per oral endoscopic myotomy vs. laparoscopic Heller myotomy, does gastric extension length matter?

OBJECTIVE: To report our experience in POEM vs. LHM, with particular focus on myotomy extension. BACKGROUND: POEM has been adopted worldwide as a treatment for achalasia. While resolution of dysphagia is above 90%, postoperative reflux ranges from 10 to 57%. Myotomy length has been a controversial topic. METHODS: Thirty-five cases of POEM were prospectively analyzed and compared retrospectively to the last 35 patients that underwent LHM, from December 2010 to August 2016. Mean follow-up was 10 months (6/32) for POEM and 20 months (6/68) for LHM. All patients with LHM had a myotomy extension ≥3 cm on the gastric side. In POEM cases, extension was defined by direct vision (Hill type II) and never exceeded 2 cm. RESULTS: Follow-up was completed in 100% of patients. Efficacy (ES ≤ 3) was 33/35 (94.2%) for POEM and 32/35 (91.4%) for LHM in a short-term follow-up (p = 1.000) and 31/35 (88.6%) and 27/35 (77.1%), respectively, in a long-term follow-up (p = 1.000), with average ES drop from 9 to 1.2 (p = 0.0001) in POEM vs. 9.2 to 1.3 (p = 0.0001) in LHM. Major Postoperative complications occurred in 1 patient (leak) for LHM and 1 patient (massive capnothorax) in POEM. Hospital stay was shorter for POEM than for LHM (1.3 vs. 2.1, respectively) (p = 0.0001). Symptomatic reflux cases included 7/35 POEM (20%) vs. 6/35 LHM (17.1%) (p = 0.4620). Esophagitis signs in endoscopy appeared in 1/21 POEM (4.7%) vs. 1/22 LHM (4.5%) (p = 1.000). Patients requiring PPI included 8/35 POEM (22.8%) vs. 7/35 LHM (20%) (p = 0.6642). Further treatment (endoscopic dilation) was performed in 10/35 POEM (28.5%) vs. 8/35 LHM (22.8%). CONCLUSIONS: A shorter myotomy on the gastric side in POEM may contribute to an acceptable reflux rate with comparable relief of dysphagia. Although our follow-up for POEM is shorter than for LHM, the trends are promising and warrant future prospective studies to address this topic.

Electrical stimulation to increase lower esophageal sphincter pressure after POEM.

INTRODUCTION: Postoperative reflux remains to be a challenge for patients with achalasia undergoing Heller myotomy. Similarly, per-oral endoscopic myotomy (POEM) is gaining rapid acceptance but the impossibility of adding a fundoplication is questioned as the main pitfall to control reflux. Electrical stimulation of the lower esophageal sphincter (LES) has emerged as a new alternative for the treatment of reflux disease. The objective of this study was to evaluate the potential benefits of combining electrical stimulation with endoscopic esophageal myotomy to prevent post procedural reflux. METHODS: Five pigs were subjected to POEM. After myotomy was completed, two electrical leads were implanted at the LES level and electrical stimulation was applied with the Endostim system with a regimen of 215 µs (5 mA amplitude), at 20 Hz for 25 min. LES pressures were recorded with manometry at pre and post-myotomy and after LES stimulation. RESULTS: Myotomy was completed successfully in all cases. Mean pre-myotomy LES pressure was 35.99 ± 8.08 mmHg. After myotomy, the LES pressure significantly dropped to 10.60 ± 3.24 mmHg (p = 0.03). Subsequent to LES-EST, LES pressure significantly increased to 21.74 ± 4.65 mmHg (p = 0.01). CONCLUSIONS: The findings of this study show that LES-EST in healthy animals increases LES pressure after POEM procedure, and could be useful tool to minimize gastroesophageal reflux.

[Radiofrequency ablation for Barrett's esophagus. Preliminary experience]. / Ablación por radiofrecuencia en esófago de Barrett. Experiencia Inicial.

UNLABELLED: Endoscopic radiofrequency ablation makes use of warm energy to ablate the esophagus's surface where the epithelial anomaly is located. PATIENTS AND METHODS: 50 adults patients with the diagnosis of EB according to Vienna Classification were included. OBJECTIVES: To evaluate the security and efficacy of ARF in patients with EB. RESULTS: 50 ARF treated patients were included with a medium follow up of 18 months. The median age was 58 years. 1.4 sessions of ARF perpatient were made to obtain EB erradication. The procedure morbidity was 6%, the more frequent complication was the esophageal stenosis (two cases). During the follow up, intestinal metaplasia recurrence was not observed. CONCLUSIONS: In the experience of our team, ARF is a secure procedure with low morbidity. These observations added to the published results help to evaluate the currentfollow up protocols.

Avances en Gastroenterología Trasplante intestinal desde la clínica a la investigación traslacional: contribuciones de una unidad integral de insuficiencia intestinal, rehabilitación y trasplante. Seguimiento biomédico del proceso de trasplante intestinal y su correlación con los distintos eventos fisiopatológicos que atraviesa el paciente.

One of the greatest achievements in gastroenterology and surgery of the last 50 years has been the capability to transplant different abdominal organs of the digestive system separately or as a whole. The complexity of the intestinal transplantation demands a multidisciplinary team engaged in the management of patients with intestinal failure responsible for defining the need for nutritional support, rehabilitation, or intestinal transplantation. This team should include a basic research area to provide answers to unresolved clinical problems. The aim of this work is to update the current status of intestinal transplantation, and to show the progress and results of our center; emphasizing our achievements in the clinical area, and the contributions of the translational research and mucosal immunology studies as part of the integral unit of intestinal failure, rehabilitation and transplantation. The data reported here demonstrate that the intestinal transplantation has been established as a therapeutic option in our country and Latin America, with long term results that have ranked our service at the level of the best centers in the world positioning us as referent in the specialty.

Immunosuppressive therapies after intestinal transplant modulate the expression of Th1 signature genes during acute cellular rejection. Implications in the search for rejection biomarkers.

BACKGROUND AND AIMS: Acute cellular rejection (ACR) and infections are leading causes of graft loss and death in intestinal transplant patients. Our aim was to evaluate the impact of maintenance immunosuppressive therapies on the expression of pro-inflammatory mediators in small bowel at ACR diagnosis. MATERIALS AND METHODS: We analyzed expression levels of Th1-associated genes, IFNG, CXCL10, and CXCL11 by qPCR in 46 selected graft biopsies unequivocally assigned to mild ACR (n = 14) or normal histopathology and clinical condition (n = 32) from 15 patients receiving two different immunosuppressive (IS) schemes. Double treatment: corticosteroids and tacrolimus (n = 17) and triple treatment: sirolimus or mycophenolate mofetil in addition to the basal therapy (n = 29). RESULTS: IFNG, CXCL10, and CXCL11 were induced during rejection (p < 0.05; p < 0.005, and p < 0.05, respectively). However, when rejection and control groups were classified according to immunosuppressive treatment, in the rejection group, significant differences of IFNG, CXCL10, and CXCL11 expression (p < 0.001; p < 0.005, and 0.01, respectively) were detected, whereas no differences were observed in the control group. CONCLUSION: Gene expression of Th1 response mediators is higher during ACR. Triple IS group showed significantly lower expression of pro-inflammatory Th1 mediators during mild ACR indicating that use of these markers to monitor rejection can be affected by the IS treatment used.

Management of early-stage esophageal neoplasia (MESEN) consensus.

BACKGROUND: Treatment of esophageal adenocarcinoma often involves surgical resection. Newer technologies in interventional endoscopy have led to a substantial paradigm shift in the management of early-stage neoplasia in Barrett's esophagus comprising high-grade dysplasia (HGD), intramucosal carcinoma, and, in some cases, submucosal carcinoma. However, there has been no consensus regarding the indications for esophageal preservation in these cases. In this work, consensus guidelines were established for the management of early-stage esophageal neoplasia considering clinically relevant aspects (age, comorbidities, and social environment) in each scenario. METHODS: Seventeen experts were invited to participate based on their background and clinical expertise at high-volume centers. A questionnaire was created that included four clinical scenarios covering a wide range of situations within HGD and/or early esophageal neoplasia, particularly where controversies are likely to exist. Each of the clinical scenarios was open to discussion subdivided by patient age (20, 50, and 80 s). For each clinical scenario an expert was chosen to defend that position. Each defense triggered a subsequent discussion during a consensus meeting. Conclusions of that discussion together with an accompanying literature analysis allowed experts to confirm or change their original choices and served as the basis for the recommendations stated in this article. RESULTS: There was 100 % consensus supporting esophageal preservation in patients with HGD, independent of patient age or Barrett's length. In patients with T1a adenocarcinoma, consensus for preservation was not reached (65 %) for young and middle-aged individuals but was supported for elderly patients (100 %). For T1b adenocarcinoma, consensus was reached for surgical resection (90 %), leaving organ preservation for patients with very low risk of nodal invasion or poor surgical candidates. CONCLUSION: Advances in endoscopic imaging and therapy allow for organ preservation in most settings of early-stage neoplasia of the esophagus, provided that the patient understands the implications of this decision.

Superficial oesophageal mucosal innervation may contribute to severity of symptoms in oesophageal motility disorders.

BACKGROUND: Mechanisms underlying perception of dysphagia and chest pain have not been completely elucidated, although oesophageal mucosal afferent nerves might play an important role. AIMS: To evaluate the relationship between oesophageal mucosal afferent nerves and the severity of dysphagia and chest pain in oesophageal motility disorders. METHODS: We prospectively recruited patients with oesophageal motility disorders having dysphagia and/or chest pain from whom oesophageal biopsies were obtained. High-resolution manometry classified patients into disorders of oesophagogastric junction (OGJ) outflow and disorders of peristalsis. Symptom severity was assessed using validated questionnaires including Brief Oesophageal Dysphagia Questionnaire (BEDQ). Immunohistochemistry was performed on oesophageal biopsies to evaluate the location of calcitonin gene-related peptide (CGRP)-immunoreactive mucosal afferent nerves. Findings were compared to existing data from 10 asymptomatic healthy volunteers. RESULTS: Of 79 patients, 61 patients had disorders of OGJ outflow and 18 had disorders of peristalsis. CGRP-immunoreactive mucosal nerves were more superficially located in the mucosa of patients with oesophageal motility disorders compared to healthy volunteers. Within disorders of OGJ outflow, the location of CGRP-immunoreactive nerves negatively correlated with BEDQ score both in the proximal (ρ = -0.567, p < 0.001) and distal oesophagus (ρ = -0.396, p = 0.003). In the proximal oesophagus, strong chest pain was associated with more superficially located mucosal nerves than weak chest pain (p = 0.04). Multivariate analysis showed superficial nerves in the proximal oesophagus was independently associated with severe dysphagia in disorders of OGJ outflow (p = 0.008). CONCLUSIONS: Superficial location of mucosal nerves in the proximal oesophagus might contribute to symptoms, especially severe dysphagia, in disorders of OGJ outflow.

Diagnosis of celiac disease during pre-operative work-up for bariatric surgery.

BACKGROUND AND AIM: Morbid obesity is a highly prevalent condition. In selected cases, bariatric surgery is indicated. Although for decades celiac disease (CD) has been associated with chronic diarrhea and weight loss, now it becomes clear that the clinical spectrum is extremely wide. METHODS: We report 5 morbidly obese patients that were diagnosed of CD during preoperative work-up for bariatric surgery. Diagnosis was suspected during routine upper endoscopy, and confirmed by histology and positive CD-specific serology. RESULT: Four of the 5 cases were asymptomatic. One complained of chronic diarrhea and anemia. All cases initiated a gluten-free diet. Due to CD, patients were offered a purely restrictive bariatric procedure. Three patients underwent a sleeve gastrectomy while the other two are still undergoing pre-operative evaluations. CONCLUSION: This report enlarges the clinical spectrum of untreated CD. Although prevalence of CD in obese patients seems to be similar to that in the general population, morbid obese patients should be tested for CD in order to establish the best surgical strategy and outcome.

Gastroesophageal reflux symptoms in patients with celiac disease and the effects of a gluten-free diet.

BACKGROUND & AIMS: Celiac disease (CD) patients often complain of symptoms consistent with gastroesophageal reflux disease (GERD). We aimed to assess the prevalence of GERD symptoms at diagnosis and to determine the impact of the gluten-free diet (GFD). METHODS: We evaluated 133 adult CD patients at diagnosis and 70 healthy controls. Fifty-three patients completed questionnaires every 3 months during the first year and more than 4 years after diagnosis. GERD symptoms were evaluated using a subdimension of the Gastrointestinal Symptoms Rating Scale for heartburn and regurgitation domains. RESULTS: At diagnosis, celiac patients had a significantly higher reflux symptom mean score than healthy controls (P < .001). At baseline, 30.1% of CD patients had moderate to severe GERD (score >3) compared with 5.7% of controls (P < .01). Moderate to severe symptoms were significantly associated with the classical clinical presentation of CD (35.0%) compared with atypical/silent cases (15.2%; P < .03). A rapid improvement was evidenced at 3 months after initial treatment with a GFD (P < .0001) with reflux scores comparable to healthy controls from this time point onward. CONCLUSIONS: GERD symptoms are common in classically symptomatic untreated CD patients. The GFD is associated with a rapid and persistent improvement in reflux symptoms that resembles the healthy population.

Acute cellular rejection in small-bowel transplantation impairs NCR+ innate lymphoid cell subpopulation 3/interleukin 22 axis.

Acute cellular rejection (ACR) remains as one of the main causes of graft loss and death in intestinal transplant (ITx) patients. ACR promotes intestinal injury, disruption of the mucosal barrier, bacterial translocation, and organ dysfunction. As epithelial regeneration is critical in reversing these consequences, the functional axis between the innate lymphoid cell subpopulation 3 (ILC3) and interleukin 22 plays an essential role in that process. Natural-cytotoxic-receptor-positive (NCR+) ILC3 cells have been demonstrated to induce intestinal-stem-cell proliferation along with an IL-22-dependent expansion of that population in several intestinal pathologies, though thus far not after ITx. Therefore, we intended to determine the impact of chronic immunosuppression and ACR on ILC3 cells and interleukin-22 (IL-22) production in the lamina propria after that intervention. MATERIALS AND METHODS: We compared biopsies from healthy volunteers with biopsies from ITx recipients without or with mild-to-moderate ACR, using flow cytometry and the quantitative-PCR. RESULTS: NCR+ ILC3 cells were found to be unaffected by immunosuppression at different time points posttransplant when patients did not experience ACR, but were diminished upon the occurrence of ACR independently of the post-ITx time. Moreover, IL-22-expression levels were notably reduced in ACR. CONCLUSION: The NCR+-ILC3/IL-22 axis is impaired during ACR contributing to a delay in or lack of a complete and efficient epithelial regeneration. Thus, our findings reveal that IL-22 analogues could potentially be used as a new complementary therapeutic approach, in conjunction with immunosuppressant drugs, in order to promote mucosal regeneration upon ACR.

Multidisciplinary approach to COVID-19 and cancer: consensus from scientific societies in Argentina.

INTRODUCTION: The world is living through an outbreak of an acute respiratory syndrome caused by a new betacoronavirus known as coronavirus 2 (SARS CoV-2), which has been declared an international public health emergency by the World Health Organisation. Cancer patients are a very special population in this setting since they are more susceptible to viral infections than the general population. Several recommendations have been made on this issue, most of them based on expert opinion and institutional experience. It is essential to gather the evidence available for decision making. OBJECTIVE: To review the evidence available in order to create a multi-institutional position from the perspective of scientific societies in Argentina involved in the management of cancer patients. METHODOLOGY: The review included two phases: 1) search and systematic revision of the medical literature; 2) consensus and revision of the document drafted by national scientific societies involved in the management and care of cancer patients using the modified Delphi method. The final results were presented at a videoconference with all the participants. Also, additional comment and recommendations were discussed. The final document was revised and approved for publication by the members of the panel. RESULTS: The consensus panel included 18 representatives from scientific societies from Argentina who assessed the evidence and then made recommendations for the management of cancer patients in our country. International guidelines (CDC; ASCO, NCCN and ESMO) were considered as a background for analysis, as well as institutional guidelines and an open ad hoc survey administered to 114 healthcare professionals from the scientific societies involved in this study.The recommendations are grouped as follows: 1) general care interventions-training of the personnel, cleaning and disinfection of the hospital premises and patient scheduling; 2) treatment decisions-patient care, surgeries, immunosuppressive therapy, radiotherapy and screening; 3) ethical considerations-optimisation of resources, end-of-life care for critically-ill patients; 4) management of hospitalised patients; and 5) wellbeing of the healthcare team.The general recommendation arising from the study is that the management of cancer patients must adapt to the exceptional pandemic status quo without disregarding treatment or cure options. Moreover, healthcare professional accompaniment of all patients should not be neglected. All healthcare professionals must make a significant joint effort to create multidisciplinary teams to discuss the most appropriate measures for each particular situation. CONCLUSIONS: The scientific evidence available on this topic worldwide is in progress. This together with the epidemiologically shifting scenario poses unprecedented challenges in the management of cancer amidst this global pandemic. Furthermore, the key role of the healthcare structural organisation appears evident, such as the drafting of clear guidelines for all the stakeholders, adaptability to constant change and an interdisciplinary shared vision through consensus to provide adequate care to our cancer patients in the light of uncertainty and fast-paced change.

Clinical utility of counting intraepithelial lymphocytes in celiac disease intestinal mucosa.

BACKGROUND/AIMS: Our aims were to establish the clinical utility of assessing the intraepithelial lymphocyte (IEL) density in intestinal biopsies from a large series of individuals and to determine the best threshold discriminating celiac disease (CD) patients and controls in two populations with different pre-test prevalence. METHODS: We prospectively performed intestinal biopsy and CD-related serology in 349 subjects undergoing upper GI endoscopy. While 116 had symptoms suggestive of a small bowel disorder (high prevalence), 233 individuals were randomly selected from patients referred to endoscopy because upper GIsymptoms (low prevalence). Diagnosis of CD was based on the concordance of classical histological features and a positive CD serology. RESULTS: While 58 patients had a newly diagnosed CD (52 in the high and 6 in the low prevalence groups), 291 subjects did not meet diagnostic criteria of the disorder. Patients had a highly significant greater IEL density than controls (p < 0.00001). Based on the ROC curve, a count of 22.8 IEL/100 epithelial cells had the highest performance for diagnosing CD in the overall population and for subjects in the high pre-test probability subgroup and 22.5% was ,he best cut-off for those diagnosed in the low risk population (area under the curves: 0.979, 0.979 and 0.993, respectively). An abnormal CD serology confirmed the diagnosis of CD in all the four patients with counts below 22.8%. CONCLUSIONS: Our study confirms that an IEL density of 22.8% is an adequate threshold to discriminate CD patients and controls in individuals irrespective of the prevalence of the disorder.

The impact of flexible endoscopy in esophageal surgery.

Achalasia and Treatment of esophageal Adenocarcinoma are commonly associated to surgical resection. Newer technologies in interventional endoscopy gave way to a substantial paradigm shift in the management of these conditions. In the case of achalasia, endoscopic myotomy is rapidly displacing Heller's myotomy as the gold standard in many centers. Early stage neoplasia in Barrett's esophagus (BE) comprising high-grade dysplasia (HGD), intramucosal and, in some cases, submucosal carcinoma is now being treated without the need of esophagectomy. This review presents a summary of the most relevant endoscopic techniques for both achalasia and esophageal cancer. Endoscopic advances in diagnostic and therapeutic arenas allow for minimally invasive therapies and organ preservation in most settings of achalasia and early stage neoplasia of the esophagus provided that the clinical setting and physician's expertise are prepared for this approach.

Clinical characteristics and long-term outcome of patients with refractory sprue diagnosed at a single institution.

BACKGROUND: Refractory sprue (RS) is a rare and severe celiac-like enteropathy not responding to a strict gluten-free diet. Although prognosis is generally poor, little is known about the long-term outcome of patients. AIM: to report baseline characteristics and long-term outcome of a series of patients diagnosed and treated in a single institution. MATERIALS: We report a retrospective cohort of 25 consecutive patients (15 females; mean age 46 yr; range 28-71) diagnosed with RS based on the presence of a non-responsive celiac-like enteropathy. All patients were intensively treated with a gluten-free diet, steroids, nutritional support and immunosupression. RESULTS: Clinical and biological characteristics of patients suggest that, at least, 24 patients had clear evidences of celiac disease. HLA DQ2/DQ8 genes were present in all the 24 patients typed and autoimmune enteropathy was excluded in all. According to the genotyping, 12 patients had a polyclonal lymphocyte population (RS type I) and 13 exhibited monoclonal TCR-gamma gene rearrangements (RS type II). Sixteen patients had evidence of ulcerative jejunitis (UJ) (7 in RS type I and 9 in type II). Overall median follow-up time after diagnosis of RS was 29 mo/patient (range 7 to 204) (45 mo for type I and 24 mo for type II). Overall mortality was 48% (12 patients), 6 in each type. Eight patients with UJ (50%), 3 with lymphoma (two T-cell and one B-cell type) and 4 (44%) without ulcers died during follow-up. The causes of death were sepsis in the context of a progressive deterioration but without overt malignancies (n=5), vascular causes (n=3) and severe malnutrition (n=1). Three- and 5-yr survival rate after diagnosis of RS for the overall population was 60% and 56%. There was no differences between type I (67%, 58%) and type II RS patients (54% for both periods). Patients with UJ had lower but non-significant 3- and 5-yr survival rates (56% and 50%, respectively) compared with patients without ulcers (78% and 66%). Survivors had a favorable outcome. While 11 patients persists asymptomatic, two other cases still have mild diarrhea and one low body weight. CONCLUSIONS: We confirm that RS is a severe celiac disease-related disorder with very high mortality. Diagnosis of overt lymphoma (12%) in our long-term follow-up was not as frequent as was reported by other groups. A proportion of patients persist in good health for a long time irrespective of the nature of the IEL infiltration or the presence of UJ.

Resección laparoendoscópica de tumor de la unión gastroesofágica / Laparoendoscopic resection of a tumor of the gastroesophageal junction

RESUMEN La resección gástrica atípica ha demostrado ser beneficiosa para tumores submucosos. La técnica pre senta mayor riesgo cuando estos se desarrollan próximos a la unión esófago-gástrica (UEG). Para esta limitación se propuso la resección intragástrica mediante una técnica mixta combinando laparoscopia y endoscopia. En nuestro medio no existen publicaciones al respecto. Se trata de una mujer de 42 años, con lesión subepitelial-subcardial de 2 cm, evaluada mediante videoendoscopia alta (VEDA), compa tible con tumor del estroma gastrointestinal (GIST) evaluado mediante ecoendoscopia. La lesión fue resecada mediante abordaje combinado laparoendoscópico. Bajo visión laparoscópica se introdujeron en cavidad abdominal trocares con balón, y bajo visión endoscópica intragástrica se introdujeron estos en el estómago y se fijó la pared gástrica a la pared abdominal insuflando dichos balones. Posterior mente se realizó la resección de la lesión con sutura mecánica. El abordaje combinado es seguro y eficaz, simple en manos entrenadas, pero constituye una opción reproducible en casos seleccionados.

ABSTRACT Atypical gastric resection has proved to be beneficial to treat submucosal tumors. The technique is more difficult when these tumors develop next to the gastroesophageal junction (GEJ). Intragastric resection combining endoscopic and laparoscopic approach was proposed to solve this limitation. There are no publications about this technique in our environment. A 42-year-old female patients with a 2-mm subepithelial tumor below the cardia evaluated by upper gastrointestinal (UGI) videoendoscopy and endoscopic ultrasound suggestive of a gastrointestinal stroma tumor (GIST) underwent resection using the combined laparo-endoscopic approach. Under laparoscopic guidance, balloon-tipped trocars were introduced in the abdominal cavity and then into the stomach using endoscopic view. The balloons were inflated to fix the gastirc wall to the abdominal wall. The lesion was resected using mechanical stapler. The combined approach is safe and efficient, and simple to perform for trained professionals, constituting a reproducible option in selected cases.

Altered Esophageal Mucosal Structure in Patients with Celiac Disease.

Background/Aim. Reflux symptoms (RS) are common in patients with celiac disease (CD), a chronic enteropathy that affects primarily the small intestine. We evaluated mucosal integrity and motility of the lower esophagus as mechanisms contributing to RS generation in patients with CD. Methods. We enrolled newly diagnosed CD patients with and without RS, nonceliac patients with classical reflux disease (GERD), and controls (without RS). Endoscopic biopsies from the distal esophagus were assessed for dilated intercellular space (DIS) by light microscopy and electron microscopy. Tight junction (TJ) mRNA proteins expression for zonula occludens-1 (ZO-1) and claudin-2 and claudin-3 (CLDN-2; CLDN-3) was determined using qRT-PCR. Results. DIS scores were higher in patients with active CD than in controls, but similar to GERD patients. The altered DIS was found even in CD patients without RS and normalized after one year of a gluten-free diet. CD patients with and without RS had lower expression of ZO-1 than controls. The expression of CLDN-2 and CLDN-3 was similar in CD and GERD patients. Conclusions. Our study shows that patients with active CD have altered esophageal mucosal integrity, independently of the presence of RS. The altered expression of ZO-1 may underlie loss of TJ integrity in the esophageal mucosa and may contribute to RS generation.