esophageal mucosal changes
The disease can occur at all ages, but the incidence seems to increase with age. Median number of neurons will be measured. Between the esophagus and the stomach is a critically important valve, the lower esophageal sphincter (LES). What does esophageal mucosal thickening mean. Biopsy specimens of acute reflux esophagitis from patients in the aforementioned clinical study of Dunbar et al exhibited significant increases in epithelial immunostaining for HIF‐2α and phospho‐p65 (an NFκ‐B subunit), as well as increases in mRNA for a number of pro‐inflammatory cytokines including IL‐8, IL‐1β, TNF‐α, and cyclooxygenase‐2.54 These biopsy specimens also demonstrated associations between levels of HIF‐2α and levels of mRNA for these pro‐inflammatory mediators, and between HIF‐2α and phospho‐p65, observations supporting the hypothesis that reflux esophagitis is initiated through a reflux‐induced, cytokine‐mediated process in which HIF‐2α plays a central role. The normal esophageal lining (squamous mucosa) is light pink or white. This review evaluates the current knowledge about the recognition of histologic esophageal mucosal changes in patients with nonerosive gastroesophageal reflux disease and analyzes the technical factors relevant to their interpretation. In support of this notion, the investigators noted increased expression of interleukin (IL)‐8, a potent pro‐inflammatory cytokine, in and around squamous cells at the luminal surface of the rat esophagus shortly after esophagodudenostomy, prior to the appearance of significant epithelial inflammation.37 Accompanying experiments using cultures of human esophageal squamous cells, which are devoid of stromal and inflammatory cells, demonstrated that brief exposure to acidic bile salt solutions did not induce cell death, but rather caused the cells to secrete IL‐8 and IL‐1β, which in turn induced migration of lymphocytes and neutrophils. Upon activation, nociceptive nerves can release CGRP and cause pain even in the absence of macroscopic injury, I have read and accept the Wiley Online Library Terms and Conditions of Use, Transient lower esophageal sphincter relaxation, The Montreal definition and classification of gastroesophageal reflux disease: a global evidence‐based consensus, Endoscopic assessment of oesophagitis: clinical and functional correlates and further validation of the Los Angeles classification, Refractory gastrooesophageal reflux disease. Mucosal inflammation is important in disease and symptom generation, and occurs due to a “cytokine sizzle” rather than due to direct caustic injury. AU and AN developed and wrote the scope of the review, DS and SS contributed to the revision of the manuscript, and RS and PW performed extensive manuscript revision. Theoretically, DIS is a morphological representation of an impaired epithelial barrier whereby the increased space between neighboring epithelial cells enables noxious refluxate contents including H+ to access nerve endings more readily and stimulate acid‐sensitive nociceptors.11 Experimental data demonstrate that DIS can be induced by acid exposure12 and DIS in GORD is resolved by therapy with proton pump inhibitors.13. Both morphologic and functional changes can be induced by exposure to refluxate-like solutions in vitro and in vivo. Acid‐sensing ion channels in gastrointestinal function, Effect of luminal acidity on the apical cation channel in rabbit esophageal epithelium, Characterization of squamous esophageal cells resistant to bile acids at acidic pH: implication for Barrett’s esophagus pathogenesis, Microscopic esophageal mucosal injury in nonerosive reflux disease, Dilated intercellular spaces and shunt permeability in nonerosive acid‐damaged esophageal epithelium, The pathogenesis of heartburn in nonerosive reflux disease: a unifying hypothesis, Acid and weakly acidic solutions impair mucosal integrity of distal exposed and proximal non‐exposed human oesophagus, Reversibility of GERD ultrastructural alterations and relief of symptoms after omeprazole treatment, Assessment and protection of esophageal mucosal integrity in patients with heartburn without esophagitis, Evaluation of oesophageal mucosa integrity by the intraluminal impedance technique, Esophageal acid exposure decreases intraluminal baseline impedance levels, In vivo evaluation of acid‐induced changes in oesophageal mucosa integrity and sensitivity in non‐erosive reflux disease, Esophageal dilated intercellular spaces (DIS) and nonerosive reflux disease, Systematic review: the role of bile acids in the pathogenesis of gastro‐oesophageal reflux disease and related neoplasia, Critical role of stress in increased oesophageal mucosa permeability and dilated intercellular spaces, Phenotypic changes in colonocytes following acute stress or activation of mast cells in mice: implications for delayed epithelial barrier dysfunction, Mechanisms by which psychologic stress alters cutaneous permeability barrier homeostasis and stratum corneum integrity, Identification and characterization of multiple corticotropin‐releasing factor type 2 receptor isoforms in the rat esophagus, The effect of life stress on symptoms of heartburn, Pathophysiology of gastroesophageal reflux disease, Visceral hypersensitivity in non‐erosive reflux disease, Role of e‐cadherin in the pathogenesis of gastroesophageal reflux disease, Altered localization and expression of tight‐junction proteins in a rat model with chronic acid reflux esophagitis, Experimental oesophagitis in the rat is associated with decreased voluntary movement, Interleukin‐6, desmosome and tight junction protein expression levels in reflux esophagitis‐affected mucosa, Role of tight junction proteins in gastroesophageal reflux disease, Roles of ZO‐1 and epidermal growth factor in esophageal epithelial defense against acid, Peptic esophagitis with duodenal or gastric ulcer, Development of consensus guidelines for the histologic recognition of microscopic esophagitis in patients with gastroesophageal reflux disease: the Esohisto project, Physicochemical basis for dilated intercellular spaces in non‐erosive acid‐damaged rabbit esophageal epithelium, Gastroesophageal reflux might cause esophagitis through a cytokine‐mediated mechanism rather than caustic acid injury, Increased expression of cytokines and adhesion molecules in rat chronic esophagitis, Cytokine‐induced neutrophil accumulation in the pathogenesis of acute reflux esophagitis in rats, Elevated levels of chemokines in esophageal mucosa of patients with reflux esophagitis, Enhanced expression of interleukin‐8 and activation of nuclear factor kappa‐B in endoscopy‐negative gastroesophageal reflux disease, Prostaglandin E(2) mediates acid‐induced heartburn in healthy volunteers, Interleukin‐1beta and interleukin‐8 expression correlate with the histomorphological changes in esophageal mucosa of patients with erosive and non‐erosive reflux disease, Gastroesophageal reflux disease‐associated esophagitis induces endogenous cytokine production leading to motor abnormalities, Esophageal epithelial‐derived IL‐33 is upregulated in patients with heartburn, Epithelial‐derived nuclear IL‐33 aggravates inflammation in the pathogenesis of reflux esophagitis, Cyclooxygenase‐2 and inflammation mediators have a crucial role in reflux‐related esophageal histological changes and Barrett’s esophagus, Association of acute gastroesophageal reflux disease with esophageal histologic changes, H+ back diffusion interferes with intrinsic reactive regulation of esophageal mucosal blood flow, Esophageal blood flow in the cat. Asian Institute of Gastroenterology, India. A 36-year-old member asked: what does esophageal mucosal thickening mean? Such research includes studies to understand the receptors by which the epithelial cells and nerves interact with the refluxate, to understand the mechanisms for afferent nerve migration and location, and to understand how inflammation interacts with nerve activation. Please remove one or more studies before adding more. Esophageal symptoms and/or injury develops when the contents of the gastro‐esophageal refluxate interface with the mucosal epithelium, leading to a chain of events that can result in epithelial barrier disruption, activation of afferent nociceptive nerves, and inflammation. Specifically "changes … You have reached the maximum number of saved studies (100). The primary pathophysiologic abnormality is a loss of the intrinsic inhibitory innervation of the lower esophageal sphincter (LES) and the segment of smooth musculature of the esophageal body. If you do not receive an email within 10 minutes, your email address may not be registered, Park SW(1)(2), Lee H(3), Lee HJ(2), Chung H(2), Park JC(2), Shin SK(2), Lee SK(2), Lee YC(2). First, while 30% of patients with pathological esophageal acid exposure have visible esophageal mucosal injury at endoscopy (erosive esophagitis, EE) and up to 10% have Barrett's esophagus, 60%‐70% of patients with GERD have no visible macroscopic injury (non‐erosive reflux disease, NERD).3 Second, symptoms do not accurately predict the severity of GERD and do not correlate well to endoscopic findings.5 Functional heartburn patients experience GERD symptoms despite having no association with reflux events, while many patients with Barrett's esophagus often do not present with heartburn despite having had years of pathological levels of acid reflux. Endometrium 1 cm. Pediatr Emerg Care. Epub 2018 Jul 12. The aim of therapy is to reduce food stasis, which might interrupt the progression to carcinoma and thus reduce the risk of squamous cell carcinoma. and you may need to create a new Wiley Online Library account. The changes of intra-esophageal pressure and long-term food stasis may lead to chronic inflammation of the esophageal mucosa,, which explained patients graded d having significantly longer disease duration than the former three grades in the EMIA classification. The size of the ganglion cells will be measured. When your esophagus was biopsied with an endoscope, the samples taken were studied under the microscope by a specialized doctor with many years of training called a pathologist.The pathologist sends your doctor a report that gives a diagnosis for each sample taken. Deep nerves in EE, however, do not express TRPV1 and may express inflammatory receptors such as bradykinin receptors as in the colon and become activated by inflammatory mediators.82, 83. The resultant denervation and reduction of post-ganglionic nerve fibers have been postulated to be related to the hypertensive or non-relaxing LES in patients with achalasia.Esophagectomy or surgical myotomy specimens have demonstratedabsence or reduction in ganglion cells as well as varying degrees of cytotoxic T-cell inflammation in the myenteric plexus of patients with achalasia. As the first line of defence against noxious gastric contents, the esophageal mucosa has a key role in disease and symptom pathogenesis in gastroesophageal reflux disease. 1.To study mucosal changes in patients with achalasia cardia [ Time Frame: 12 weeks ], 2. The mean Ki-67 and mean p53 positive ratio will be measured in the histopathological examination. No currently available treatment options result in regeneration of myenteric neurons to bring back esophageal motility. Graded pneumatic balloon dilatation (PBD) has replaced conventional one-time dilatation and open Heller's myotomy has cleared the way for laparoscopic Heller's myotomy (LHM) with fundoplication.Recently, per oral endoscopic myotomy (POEM) was introduced by Inoue et al. Esophageal mucosal changes in long standing achalasia cardia and reversibility after per oral endoscopic myotomy - A pilot study, •All patients of achalasia cardia who will undergo POEM and an esophageal mucosal biopsy at 3 months of follow up. All authors reviewed the final version of the manuscript. We discuss the current understanding of the mucosal response to acid injury, the nociceptive role of acid‐sensitive receptors expressed in the esophageal mucosa, and the role of esophageal epithelial cells in initiating the onset of erosive esophagitis. Transient receptor potential vanilloid type‐1 (TRPV1) is a non‐selective Ca2+‐permeant channel that has been widely proposed to be a candidate sensory transductor of reflux‐induced symptoms since it can be activated by acid and is often involved in pain pathways.26, 55-57 Neutrophils and other immune cells can also release protons from their exocytic granules and lysosomes into the microenvironment58-60 and this inflammation‐induced microenvironment acidification conceivably could activate TRPV1 even in the absence of reflux episodes.61-63 TRPV1 expression has been demonstrated to be increased in biopsies taken from GERD patients compared to controls.64 Acid‐activation of TRPV1 in cat esophageal mucosa has been shown to result in release of substance P and CGRP, strongly implicating a nociceptive role.65 Similarly, TRPV1 activation in cultured human esophageal epithelial cells has been shown to result in the release of adenosine triphosphate (ATP), a neurotransmitter involved in pain signaling and inflammation.66 Moreover, a recent in vivo study demonstrated reduced acid‐induced damage to the mucosal integrity of murine esophageal epithelium upon pharmacological blockade of TRPV1, suggesting a potential role for TRPV1 in mucosal barrier impairment in NERD.67 The protease‐activated receptor 2 (PAR2): a receptor for trypsin, is reportedly upregulated in the esophageal mucosa of GORD patients, coupled with the expression of inflammatory mediators such as IL‐8.68, 69 The acid‐induced activation of PAR2 has been shown to enhance ATP release from cultured esophageal epithelial cells, to increase TRPV1 phosphorylation, and to lead to heightened sensitivity to acid.66, Other TRP channels may also be candidates for sensory transduction in the esophageal mucosa. Understanding Your Pathology Report: Esophagus With Reactive or Reflux Changes, Not Including Barrett’s Esophagus. We therefore sought to identify reflux-induced changes in mucin gene expression using a cell line and biopsies from the esophageal mucosa in … Talk to a doctor now. Learn about our remote access options, Wingate Institute of Neurogastroenterology, Barts and the London School of Medicine and Dentistry, Queen Mary University of London, London, UK, Department of Medicine, Center for Esophageal Diseases, Baylor University Medical Center and Center for Esophageal Research, Baylor Scott & White Research Institute, Dallas, TX, USA. In this same study, Dunbar et al assessed the esophageal mucosa with confocal laser endomicroscopy (CLE), which demonstrated significant increases in intercellular space width in the proximal and distal esophagus as esophagitis developed. Surgical myotomy has been thought to be the curative therapeutic choice for symptomatic achalasia. Dr. Ed Friedlander answered. induced acute reflux esophagitis in 12 patients who had severe (Los Angeles grade C) EE healed with PPIs by stopping PPI therapy for 2 weeks.48 From baseline to 2 weeks off PPIs, GERD redeveloped quickly in these patients manifested by significant increases in their GERD‐Health Related Quality of Life symptom scores and in their esophageal acid exposure times; endoscopic evidence of reflux esophagitis also was observed to develop in all 12 patients within 2 weeks.48 Esophageal biopsies (taken from areas without surface erosions) at 1 and 2 weeks off PPIs demonstrated increases in intraepithelial T lymphocytic infiltration; neutrophils and eosinophils were rare. During POEM, a mucosal biopsy and a muscle biopsy of the Esophagus will be taken. These findings will be measured 12 weeks post POEM. Diversatek Healthcare, in conjunction with Vanderbilt University, developed the MiVu Mucosal Integrity Testing System to detect changes in esophageal mucosal integrity simply and efficiently. 26 Ashfield Street, London E1 2AJ, UK. The morphological integrity of the esophageal mucosa is defined by equilibrium between aggressive factors and protective mechanisms. Philip Woodland, Wingate Institute of Neurogastroenterology, Centre for Neuroscience and Trauma, Blizard Institute, Barts and the London School of Medicine and Dentistry, Queen Mary University of London. Our understanding of how these aggressive constituents lead to symptoms and injury in GERD has evolved over recent years, perhaps moving from a more simplistic view of barrier disruption and mucosal permeability to acid toward a more complex view, integrating this permeability change with epithelial cell and neuronal activation alongside cytokine‐driven mucosal injury. It also illustrates that more research is needed to fully understand the role and nature of the interaction between the gastro‐esophageal refluxate and the mucosal epithelium, afferent nerves, and inflammatory pathways. After esophageal epithelial exposure to acid, induction of inflammation and symptoms is likely, at least in part, to be transduced via acid‐sensitive receptors expressed within the mucosa. Achalasia Cardia is a potential pre-malignant condition which can lead to esophageal carcinoma. In Barrett's esophagus, tissue in the tube connecting your mouth and stomach (esophagus) is replaced by tissue similar to the intestinal lining.Barrett's esophagus is often diagnosed in people who have long-term gastroesophageal reflux disease (GERD) — a chronic regurgitation of acid from the stomach into the lower esophagus. Symptoms will be classified by using the Eckardt score.Type of Achalasia will be classified according to the Chicago classification. Endoscopic mucosal resection for esophageal and gastric mucosal cancers Haruhiro Inoue MD DIAGNOSIS OF EARLY ESOPHAGEAL CANCER Detection of early stage esophageal cancer: Normal eso-phageal mucosa usually appears at endoscopy as smooth and flat, with a whitish lustrous surface. If the lining is salmon-pink in color, it is likely Barrett’s esophagus. MiVu™, only from Diversatek Healthcare, detects esophageal mucosal changes due to chronic GERD or EoE instantly during routine endoscopy, potentially obviating the need for 24- to 48-hour ambulatory pH monitoring or esophageal biopsies for histopathology, reducing both diagnostic and treatment latency. Introduction Changes in the expression of mucin genes in the esophageal mucosa associated with uncomplicated gastro-esophageal reflux disease have not been evaluated even though such changes could be associated with reflux-induced mucosal damage. Studies demonstrating an association between achalasia and certain HLA phenotypes, and an increased immunologic response to Herpes Simplex Virus-1 (HSV-1) in the serum and LES myenteric plexusof achalasia patients further support the notion of inflammation playing a central role in pathogenesis.However, it is not known whether this inflammation is part of the process that leads to the loss of the plexus, or whether it is secondary to the outflow obstruction with consecutive stasis in achalasia. Furthermore, these studies suggested that biopsies from patients with GERD had a greater reduction in TER upon acid exposure than biopsies from control subjects, perhaps suggesting an inherent vulnerability to barrier dysfunction in GERD.14 However, the presence of transient DIS alone is unlikely sufficient for symptoms (perfusion‐induced DIS in healthy volunteers does not induce symptoms.12 Symptom generation is likely to require a long‐lasting DIS, allowing prolonged epithelial exposure to noxious stimuli. This histologic finding suggests that myasthenic changes in esophageal muscles may lead to dysphagia. Achalasia cardiais a rare, chronic, esophageal motility disorder with an estimated annual prevalence of 1 per 1,00,000 subjects. i However, lowering LES pressure can significantly reduce symptoms and improve quality of life. Barrett's esophagus is a condition in which the flat pink lining of the swallowing tube that connects the mouth to the stomach (esophagus) becomes damaged by acid reflux, which causes the lining to thicken and become red. (normal size of ganglion cells is 10 to 40 microns). (normal size of ganglion cells is 10 to 40 microns). First, the esophageal lining must have a certain appearance on an upper endoscopy exam. Persistent esophageal distension with retention of foods and fluids, bacterial overgrowth, and impaired clearance of regurgitated acid and gastric contents lead to chronic inflammation and passively cause dysplasia and carcinoma. The endoscopic abnormalities that may be seen in association with esophageal disorders are numerous, varying from subtle alterations in the esophageal mucosal surface to large ulcers or masses. Ahmed Osman H(1), Aly SS(2), Mahmoud HS(1), Ahmed EH(3), Salah Eldin EM(4), Abdelrahim EA(5), El Masry MA(6), Herdan RA(7), Hassan MH(8). This paper demonstrates that much progress has been made in the understanding of the mucosal changes that develop after the occurrence of excessive gastro‐esophageal reflux. mucosal damage is testified by endoscopic changes and histology adds no new information regarding the etiology of esophagitis (acid and/or nonacid reflux, drug ingestion). Even in non‐erosive reflux disease, the esophageal mucosal barrier is defective when compared to healthy controls. While Claudin‐3 expression decreases, Claudin‐1 and Claudin‐2 become upregulated in EE only.29, 32 In addition, acid exposure reduced the expression of tight junction protein 1 (ZO‐1) by human esophageal epithelial cells, whereas incubation with epithelial growth factor reversed this effect and inhibited barrier function impairment.33, For years, the pathogenesis of esophageal mucosal inflammation in GERD was thought to proceed in a “top‐down” fashion, with acid‐peptic injury starting at the luminal surface.34 According to this traditional acid burn model of EE, the process begins with refluxed acid and pepsin damaging proteins in the tight and adherens junctional complexes between esophageal squamous cells, thus enabling hydrogen ions (i.e., acid) to penetrate the epithelium and kill the cells at the luminal surface. Before POEM, all patients will undergo symptom evaluation, esophagogastroduodenoscopy (EGD), high resolution esophageal manometry and timed barium esophagogram.The diagnosis of achalasia will be based on a combination of clinical presentation, esophagogastroduodenoscopy, barium esophagogram and high resolution manometric findings. Hyperplasia of basal cells was evident by week 1, but surface cell death (i.e., erosion) was not detected until week 4, indicating that the death of surface cells was not the trigger for basal cell hyperplasia. Symptoms and complications occur due to contact of noxious components of the refluxate with the esophageal mucosa. However, a significant contribution to the pathogenesis of GERD and potentially the variability in disease expression may be explained at the mucosal level. The purpose of this review is to consider the crosstalk of different factors of the esophageal mucosa in the pathogenesis of GERD, with a particular focus on mucosal innervation and molecular basis of acid‐induced cytokine response. esophageal mucosal changes. [14,15] The prevalence of the disease is not certain, but is estimated to be 1-4 … 1 cm polyp colon. Esophageal mucosal changes in children with an acutely ingested coin lodged in the esophagus. Under normal circumstances, the threat imposed by noxious refluxate is met by mucosal defense mechanisms including local homeostatic repair induced by acid‐sensing epithelial cells and neurons.6 The stratified squamous epithelium of the esophagus itself provides a tight protective barrier against luminal contents.7 Junctional complexes between esophageal epithelial cell membranes are composed of tight junctions, adherens junctions, and desmosomes which form a barrier against the diffusion of ions.8 Where macroscopic erosions are visible (i.e., EE) there is clear evidence of mucosal barrier deficiency. Learn more. Hence no power calculation is used to estimate the sample size. 1 cm fibroid. MiVu™, only from Diversatek Healthcare, detects esophageal mucosal changes due to chronic GERD or EoE instantly during routine endoscopy, potentially obviating the need for 24- to 48-hour ambulatory pH monitoring or esophageal biopsies for histopathology, reducing both diagnostic and treatment latency. Luminal acid‐induced activation of a disintegrin and metalloproteinase (ADAM‐10) and its subsequent cleavage of the adherens junction protein e‐cadherin have been identified as major contributors of a disturbed junctional barrier in the esophageal epithelium.28 In line with the association between enhanced mucosal permeability and GERD pathophysiology, in vitro and animal studies have also described the dysregulation of tight junction molecules.29-31 A rat model of EE identified interleukin‐6 as a mediator for the downregulation of desmosomes, the onset of DIS, and subsequently defective cell‐cell contacts.31 Moreover, distinct patterns of localization and expression of tight junction proteins (Occludin, Claudin‐1‐4) have been described. Endoscopic balloon dilatation is still widely performed because of its relative non-invasiveness and simplicity, but it has a relatively lower success rate and often requires multiple treatment sessions. Finally, although acid suppression with proton pump inhibitors (PPIs) is effective for many, over 30% of patients respond inadequately.2, 4, 5. Choosing to participate in a study is an important personal decision. Number of ganglion cells will be measured in the mucosal biopsy (normal number of ganglion cells are 2 to 12 per mm on Histopathological examination). The components of the gastro‐esophageal refluxate can vary, and systemic factors (e.g., psychological stress) will influence symptoms perception. These ions generate an osmotic force that drags water from the lumen into the intercellular spaces, pushing the epithelial cells apart and thus creating DIS.36. Methods: Between January 1, 1992, and August 31, 1994, the senior author (JFF) performed 255 esophageal biopsies. The cycle continues. ... that was lodged in the esophagus to determine the degree of compromise of the esophageal mucosal integrity. Although acid is believed to be the primary aggressor within the refluxate, other components including bile acids (from duodeno‐gastro‐esophageal reflux) and pepsin have also been implicated. The etiology and pathogenesis of achalasia is still unknown. Working off-campus? This article discusses the current understanding of the mucosal pathogenesis of GERD. Principal investogator want to study the pre-malignant and malignant changes in the Esophagus in achalasia cardia patients. Integrity of the epithelial barrier, and presence of acid‐sensitive receptors and nerves, and mucosal inflammation are likely to play an overlapping, often interdependent, role in pathogenesis of esophageal pain and sensitivity. Surgical myotomy has been thought to be the curative therapeutic choice for symptomatic achalasia. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Pediatr Emerg Care. All coins were removed by endoscopic forceps extraction, with direct inspection of esophageal mucosa. Functional changes in esophageal mucosal permeability can be demonstrated in vivo using intraluminal impedance techniques. Bonadio WA(1), Emslander H, Milner D, Johnson L. Author information: (1)Children's Hospital of … Endoscopic balloon dilatation is still widely performed because of its relative non-invasiveness and simplicity, but it has a relatively lower success rate and often requires multiple treatment sessions. However, it requires skin incisions and additional anti-reflux surgical intervention.Unlike surgical myotomy, POEM preserves the anatomical integrity of the LES and possibly minimizes postoperative reflux. Moreover, the localization and characterization of mucosal afferent nerves vary between GERD phenotypes and could explain the heterogeneity of symptom perception between patients who experience similar levels of acid reflux. MiVu™, only from Diversatek Healthcare, detects esophageal mucosal changes due to chronic GERD and EoE, and as importantly, MiVu provides objective evidence of no inflammatory disease. Unzureichende Symptomkontrolle unter Langzeittherapie mit PPI bei GERD — Fakt oder Fiktion?Insufficient symptom control under long‐term treatment with PPI in GERD — fact or fiction? In this model, the first evidence of esophageal inflammation observed was a T‐lymphocyte infiltration of the submucosa three days after the operation. • Patients of achalasia cardia not undergoing POEM or an esophageal mucosal biopsy at 3 months of follow up. ClinicalTrials.gov Identifier: NCT04463095, Esophageal Mucosal Changes in Long Standing Achalasia Cardia and Reversibility After Per Oral Endoscopic Myotomy ( POEM ), 18 Years to 75 Years (Adult, Older Adult), Contact: Dr Pranav Milind Ambardekar, MBBS MD, Contact: Mr Rajesh Goud Maragoni, MPharma, MBA, Asian institute of Gastroenterology/AIG Hospitals, Contact: Dr Pranav Milind Ambardekar, MBBS MD 04023378888, Contact: Rajesh Goud Maragoni, Mpharma,MBA 04023378888 ext 802, Principal Investigator: Dr Pranav Milind Ambardekar, MBBS, MD, Mohan Ramchandani, Dr, Asian Institute of Gastroenterology, India.