Esophageal Adenocarcinoma Methods and Protocols

143

Alfred K. Lam (ed.), Esophageal Adenocarcinoma: Methods and Protocols, Methods in Molecular Biology, vol. 1756,
https://doi.org/10.1007/978-1-4939-7734-5_13, © Springer Science+Business Media, LLC 2018

Chapter 13

Animal Model: Reflux Models in Esophageal

Adenocarcinoma

Takahiro Masuda and Sumeet K. Mittal

Abstract

Many mouse models have been developed to mimic the inflammation–metaplasia–dysplasia–carcinoma
sequence seen in the gastroesophageal reflux disease (GERD)–Barrett’s esophagus–esophageal adenocar-
cinoma progression. Surgical reflux models in mice are technically challenging due to the small size and
intolerance to surgical stress of mice. Herein, we detail three representative surgical procedures that allow
for creation of an esophageal adenocarcinoma model in mice, either with or without the use of carcino-
gens. Additionally, we describe a genetic model that shows spontaneous development of esophageal
adenocarcinoma.

Key words Animal model, Barrett’s esophagus, Esophageal adenocarcinoma, Esophagoduodenal

anastomosis, Esophagojejunostomy, Gastroesophageal reflux disease, Genetic model, Mouse, Surgical

model

1 Introduction

Esophageal cancer is a devastating cancer, with an incidence rate of

4.3 per 100,000 persons in the United States. The histological

subtype adenocarcinoma accounts for 60% of all cases of esopha-

geal cancer [ 1 ]. The incidence rate of esophageal adenocarcinoma

is rapidly increasing in this country [ 2 ], in contrast with the declin-

ing trends associated with most other cancer types [ 3 ]. Despite

advances in multimodality treatment, the prognosis of esophageal

adenocarcinoma remains poor, with less than 30% of individuals

with esophageal adenocarcinoma reaching 5-year survival [ 4 ].

Esophageal adenocarcinoma develops in a predictable, sequen-

tial manner: through a metaplasia–dysphagia–carcinoma sequence.

Almost all esophageal adenocarcinomas have developed from

Barrett’s esophagus, the metaplastic condition in which normal

squamous epithelium is replaced by incomplete intestinal colum-

nar epithelium [ 5 ]. Barrett’s esophagus occurs secondary to

chronic gastroesophageal reflux disease (GERD) in the lower