Clinical Trial Details
— Status: Completed
Administrative data
| NCT number |
NCT04463095 |
| Other study ID # |
POEM EM |
| Secondary ID |
|
| Status |
Completed |
| Phase |
|
| First received |
|
| Last updated |
|
| Start date |
June 30, 2020 |
| Est. completion date |
September 1, 2021 |
Study information
| Verified date |
July 2020 |
| Source |
Asian Institute of Gastroenterology, India |
| Contact |
n/a |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Observational
|
Clinical Trial Summary
Esophageal mucosal changes in long standing achalasia cardia and reversibility after per oral
endoscopic myotomy - A pilot study
Aims and Objectives:
- To study mucosal changes in patients with achalasia cardia
- To study potential malignant histopathological findings in long standing achalasia
cardia
- To assess reversibility of mucosal changes after POEM
- To study co-relation of mucosal histopathology with predictors of sub-mucosal fibrosis
- To study muscle biopsy by light microscopy and electron microscopy for viral inclusions
Materials and Methods:
- Study Area - Patients of achalasia cardia undergoing POEM in Asian Institute of
Gastroenterology.
- Study Design - Cross sectional study
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
- End Point( Length of follow up )- 3 months after POEM - single follow up.
Study Procedure:
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.
Symptoms will be classified by using the Eckardt score.Type of Achalasia will be classified
according to the Chicago classification. Esophagus shape (sigmoid vs nonsigmoid), presence of
hiatus hernia, presence of esophagitis will be assessed on esophagogastroduodenoscopy.
Duration since first symptoms of achalasia will be recorded.
All patients fulfilling the inclusion criteria will undergo Per Oral Endoscopic Myotomy
(POEM). During POEM, a mucosal biopsy and a muscle biopsy of the Esophagus will be taken.
Patients will be followed up at a single time, 3 months after POEM. During the follow up
visit, patients will undergo esophagogastroduodenoscopy guided mucosal biopsy of the
Esophagus. Patients will be divided into two groups based on the duration of symptoms of
achalasia- Those having symptoms for 1 year or less and those having symptoms for more than 5
years. Histopathological changes in the Esophagus and reversibility of these changes after
POEM will be compared between the two study groups to draw a conclusion.
Description:
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.
