The severity of duodeno‐esophageal reflux influences the development of different histological types of esophageal cancer in a rat model

Abstract

The mechanism through which each histological type of carcinoma arises from the esophageal mucosa remains unknown. This study was designed to investigate whether there is an association between the severity of duodeno-esophageal reflux and the histological type of esophageal cancer. A series of 120 male Fischer rats, weighing~180 g, were randomized to receive one of the following procedures: duodeno-forestomach reflux (DFR) with reduced exposure to duodenal contents, duodeno-esophageal reflux (DER) with increased exposure to duodenal contents and three control operations (DFR, DER control and sham). The reflux of bile was estimated with 99m Tc-PMT scintigraphy. All animals were fed a standard diet without carcinogen. The esophageal mucosa was assessed 50 weeks after surgery for carcinoma. The median scanned fraction rate of duodeno-esophageal reflux was significantly lower for the rodents in the DFR group than those in the DER group. Five of 28 rodents in the DFR group and 17 of the 22 rodents in the DER group developed esophageal carcinoma. None of the controls developed carcinoma. The five rodents in the DFR group developed SCC. Of 22 esophageal carcinomas for the DER group, nine were SCC, 12 ADC and one was adenosquamous carcinoma. The fraction of esophageal SCC for the DFR group was significantly higher than that for the DER group, while the fraction of esophageal ADC for the DFR group was significantly lower than that for the DER group. These observations suggest that the severity of duodeno-esophageal reflux in rodents is related to the development of different histological types of esophageal carcinoma.Esophageal squamous cell carcinoma (ESCC) and esophageal adenocarcinoma (EADC) are the two main histological types of esophageal cancer. 1 Population based studies in the Western world have shown steady and rapid rise in the incidence of EADC. 1,2 In contrast, the incidence of ESCC, the most common histological type of cancer in the Eastern world, remains stable. 3 The cause of the increased incidence of esophageal cancer remains obscure.A rise in EADC may be related to an increase in the incidence of gastroesophageal reflux disease (GERD) over the past few decades. Population studies have demonstrated a strong and causal relation between GERD and risk of developing EADC. 4 Data from a large multicenter US study identified four major risk factors for EADC: GERD, obesity [as measured by body mass index (BMI)], cigarette smoking and a diet low in fruits and vegetables. 4,5 The progression of GERD to EADC involves the initial development of inflammation induced hyperplasia and metaplasia at the gastro-esophageal junction. This is followed by multifocal dysplasia and ADC. 6 The relationship between ESCC and GERD has not been investigated or reported. Prior studies support the hypothesis that GERD plays a role in laryngopharyngeal carcinogenesis. 7,8 A population-based cohort study of patients who underwent gastrectomy for peptic ulcer disease showed a long-term increased risk of laryngeal and pharyngeal cancer....

Correlation of precancerous lesion incidence with duodenogastric reflux and N-nitroso compound duration at reflux and antireflux stomach surgery: An experimental study

“…The superficial part between the epithelial border and the proliferating work creates certain protection against the carcinogens entering from the gastric lumen into the mucosa. Mucous erosion in the antrum, probably represent an increased risk of carcinogenesis, by increasing the probability of cell proliferation and by reducing the density of the mucosa above the proliferative portion 21 .…”

Impact of histone deacetylase 1 and metastasis-associated gene 1 expression in esophageal carcinogenesis

“…In brief, high exposure to duodenal contents promotes the development of EADC, and low exposure induces ESCC. The severity of the duodenoesophageal reflux in rodents is associated with the development of different histological types of esophageal carcinoma (11). In the present study, ESCC was shown to arise from dysplastic changes to squamous cells that were naturally located proximal to the columnar-lined epithelium.…”

“…The rat model demonstrated the histopathological sequence of events from GERD to EADC as an inflammation-metaplasia-dysplasia-adenocarcinoma (ADC) sequence. Furthermore, a recent study has established a correlation between the quantity of reflux and the likelihood of developing EADC and ESCC (11). …”

Roles of the hexosamine biosynthetic pathway and pentose phosphate pathway in bile acid‐induced cancer development

“…After fasting for 24 h, a midline laparotomy incision was made under inhalation anesthesia. Reflux of duodenal contents was induced according to previously reported procedures (Figure ).…”