Esophageal Mucosal Changes in Achalasia Cardia and Reversibility After Per Oral Endoscopic Myotomy - A Pilot Study

Introduction and Background:

Achalasia cardiais a rare, chronic, esophageal motility disorder with an estimated annual prevalence of 1 per 1,00,000 subjects. The disease can occur at all ages, but the incidence seems to increase with age. The predominant symptoms are dysphagia and regurgitation, because of the impaired relaxation of the lower esophageal sphincter (LES) and the loss of normal peristalsis.Achalasia is a neurodegenerative disease resulting from an inflammatory and/or autoimmune process ultimately leading to aganglionosis. The etiology and pathogenesis of achalasia is still unknown. 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. 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. 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. 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 prognosis of patients who develop such carcinomas remains poor. 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.

No currently available treatment options result in regeneration of myenteric neurons to bring back esophageal motility. However, lowering LES pressure can significantly reduce symptoms and improve quality of life. To achieve this outcome (LES pressure reduction), therapeutic techniques have been modified from time to time. 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. as a less invasive and effective curative treatment option with minimal complications.Peroral endoscopic myotomy (POEM)combines thelong-term efficacy of a myotomy with the benefits of an endoscopic, minimally invasive procedure.Other therapeutic options include endoscopic balloon dilatation and surgical myotomy. 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. Surgical myotomy has been thought to be the curative therapeutic choice for symptomatic achalasia. 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.

Rationale of the study:

• There have been very few studies systematically analysing the histopathological changes in the mucosa and muscle of the Esophagus in Achalasia Cardia.
• Therefore we want to study the histopathological changes in the mucosa and muscle of the Esophagus in achalasia cardia patients and observe how the histopathological changes differ between early achalasia cardia and long-standing achalasia cardia.
• Achalasia Cardia is a potential pre-malignant condition which can lead to esophageal carcinoma.
• Principal investogator want to study the pre-malignant and malignant changes in the Esophagus in achalasia cardia patients.
• Also want to study whether per oral endoscopic myotomy ( POEM ) reverses the histopathological and pre-malignant changes in the Esophagus.

Inclusion criteria

• • All patients of achalasia cardia who will undergo POEM and an esophageal mucosal biopsy at 3 months of follow up

Exclusion criteria

• • Patients of achalasia cardia not undergoing POEM or an esophageal mucosal biopsy at 3 months of follow up

• Upper gastro-intestinal surgically altered anatomy ( apart from previous Heller Myotomy )
• Pregnancy
• Patients not giving consent for participation