Aflatoxin influences achalasia symptomatology

Lin,Shengli; Gao,Pingting; Li,Quanlin; Zhang,Yiqun; Hu,Jianwei; Cai,Mingyan; Qin,Wenzheng; Ma,Lili; Ren,Zhong; Zhang,Zhen; Cai,Xianli; Yao,Liqing; Chen,Weifeng; Zhou,Pinghong

doi:10.3892/mmr.2020.10914

Aflatoxin influences achalasia symptomatology

Authors:
- Shengli Lin
- Pingting Gao
- Quanlin Li
- Yiqun Zhang
- Jianwei Hu
- Mingyan Cai
- Wenzheng Qin
- Lili Ma
- Zhong Ren
- Zhen Zhang
- Xianli Cai
- Liqing Yao
- Weifeng Chen
- Pinghong Zhou
View Affiliations

Affiliations: Endoscopy Center and Endoscopy Research Institute, Zhongshan Hospital, Fudan University, Shanghai 200032, P.R. China
Published online on: January 8, 2020 https://doi.org/10.3892/mmr.2020.10914
Pages: 1276-1284
Copyright: © Lin et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Achalasia is characterized by impaired swallowing due to lower esophageal sphincter (LES) dysfunction and an increased risk of esophageal carcinoma. Aflatoxin is a known carcinogen. Esophageal retention is relieved by per oral endoscopic myotomy (POEM), which lowers the esophageal cancer risk. The present study determined whether aflatoxin is involved in the pathogenesis of achalasia or esophageal cancer. A total of 75 patients with achalasia were prospectively enrolled from a tertiary center. Aflatoxin levels in their esophageal contents were measured using ELISA, and esophageal mucosal specimens were immunohistochemically evaluated for Ki67 and p53 expression prior to and 3 months after POEM. The effect of aflatoxin on esophageal contractility was assessed using murine specimens. Aflatoxin was detected in 67 patients before POEM and only 2 patients after POEM. The number of Ki67‑ and p53‑immunopositive cells in the esophageal mucosa significantly decreased after POEM: [Ki67: 27.8% (95% confidence interval (CI), 25.98‑29.70) vs. 20.7% (95% CI, 19.78‑24.03), P=0.04 and p53: 2.14% (95% CI, 1.85‑2.41) vs. 1.45% (95% CI, 1.22‑1.68), P=0.03]. In vitro experiments revealed that 500 ng/ml aflatoxin significantly increased the amplitude (P<0.05) and frequency (P<0.05) of spontaneous LES contractions compared with the control group. These increases were blocked by co‑treatment with atropine sulfate (P<0.05), but not with a nitric oxide synthase inhibitor (P>0.05). Aflatoxin was found in most patients with achalasia and was eliminated following POEM. Reduced Ki67 and p53 expression after POEM indicated a decreased risk of carcinogenesis. Aflatoxin accumulation increased LES contractility via cholinergic signaling. Therefore, aflatoxin may maintain achalasia symptoms and increase esophageal cancer risk.

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