Histopathological Analysis of Esophageal Mucosa in Patients with Achalasia

Abstract

Background/Aims Achalasia is an esophageal motor disorder that leads to functional esophageal obstruction. Food stasis and bacterial fermentation can predispose an individual to esophageal mucosal inflammation, causing multifocal dysplasia and increasing the risk of developing esophageal squamous cell carcinoma. We aimed to evaluate esophageal mucosal alterations in achalasia patients and determine clinical factors associated with the histopathological findings. Methods From 2009 to 2013, we obtained endoscopic biopsies from the lower and middle esophagus of 22 patients with achalasia and 17 controls. Patients’ clinical data and histological severity of esophagitis were retrospectively analyzed. Additionally, immunohistochemical staining for CD3, CD20, Ki-67, and p53 was conducted. Results The median age of achalasia patients was 49.5 years (range, 27 to 82 years), and there were nine males (40.9%). The median symptom duration was 5.8 years (range, 1 to 33.5 years), and 10 patients (45%) underwent previous treatment (nine, balloon dilation; one, botulinum toxin injection). Achalasia patients had significantly more severe esophagitis than did controls (p=0.001, lower esophagus; p=0.008, middle esophagus), and the number of CD3-positive lymphocytes exceeded that of CD20-positive lymphocytes (p<0.001). Achalasia patients also had a higher esophageal Ki-67 proliferation index (p=0.048). Although statistically nonsignificant, p53 expression was only observed in achalasia patients. There was no association between the histological severity of esophagitis and other clinicopathological findings. Conclusions Achalasia patients showed significantly severe histological esophagitis and a high Ki-67 proliferation index, indicating an increased risk of neoplastic progression. Therefore, careful endoscopic inspection is necessary for the early detection of superficial neoplasia in these patients. (Gut Liver 2021;15-722)

RNA-sequencing reveals molecular and regional differences in the esophageal mucosa of achalasia patients

“…Over time this predisposes to chronic inflammation and increases the risk of developing esophageal squamous cell cancer 3,4 . Furthermore, our study confirms the presence of esophagitis previously reported in histological studies of the esophageal mucosa in achalasia [17][18][19] , which we confirmed in our study as well.…”

Endoscopic Surveillance in Idiopathic Achalasia

“…The study found significantly higher levels of inflammation, a greater number of CD3-positive than CD20-positive lymphocytes, and a higher Ki-67 proliferation index in patients with achalasia. The tumor suppressor gene p53, although statistically non-significant in this study, was noted in only achalasia patients [ 19 ]. Other studies with larger cohorts have shown statistically significant associations with the p53 gene in borderline dysplastic and carcinoma in situ lesions in achalasia patients [ 18 , 20 ].…”

Cancer Risk in Patients With Achalasia

“…This was confirmed histologically, and the lower esophageal biopsies showed higher Ki-67 proliferation, though no statistically significant difference in p53 expression when compared with controls. 18 Leeuwenbergh et al found that early surveillance biopsies demonstrated p53 overexpression in 82% of a small cohort of achalasia patients who ultimately developed SCC or high-grade dysplasia. On the other hand, the study by Leeuwenburgh et al did not show a significant difference in Ki-67 proliferation when compared to controls.…”