Diet composition affects surgery-associated weight loss in rats with a compromised alimentary tract

Abstract

Background: Esophageal adenocarcinoma (EAC) is the fastest growing cancer in terms of incidence and has a high mortality rate. The animal model to study EAC uses esophagoduodenal anastomosis (EDA) to induce mixed-reflux (bile/acid) causing esophagitis, Barrett's esophagus, and EAC sequence within 6 mo. However, the lack of fully functional stomach in these rats leads to the development of malnutrition.

Methods: We have assessed the ability of a chemically pure, purified ingredient diet (AIN-93M) to reduce surgery-associated malnutrition in rats that have undergone the EDA-surgery. Animals were either sham- (SH) or EDA-operated and fed either a grain-based rodent diet (RD) (SH-RD, n=3; EDA-RD, n=10) or a purified diet (PD) (SH-PD, n=4; EDA-PD, n=11). The animals were weighed periodically for assessment of weight gain and euthanized at the end of 24 wk to measure esophageal tumor incidence.

Results: Animals that underwent sham surgery continued to gain weight throughout the study period and no tumors were detected. The EDA-operated animals had significantly lower weight gain compared with sham animals. There was no significant difference in weight gain among EDA animals fed two different types of diets until 9 wk after the surgery. After 9 wk, EDA-RD continued to lose weight significantly, whereas the weight loss leveled in EDA-PD (P<0.001). At termination, neither tissue histopathology nor tumor incidence was significantly different between the groups.

Conclusion: These results show that compared with a natural ingredient diet, a purified ingredient diet can reduce surgery-associated weight loss in rats with a compromised alimentary tract. This reduction in malnutrition has the potential to reduce the confounding effects of weight loss on future animal studies reported.

Figure 1. Effect of diet and EDA-surgery on body weight gain in male SD rats

Rats were fed either RD (solid symbols) or PD (open symbols) and operated with SH-(circles) or EDA- surgery (squares). The surgery was performed on week 0 and weight gain was recorded periodically for 24 weeks. SH-RD (solid circles); EDA-RD (solid squares); SH-PD (open circles) and EDA-PD (open squares). #- Significantly different from SH-operated animals on respective diets (p<0.001) § - Significantly different from EDA-PD (p<0.001)

Figure 2. A–D Histological changes in the esophageal epithelium after esophagoduodenal anastomosis (EDA) in rats fed purified diet

A- Normal esophagus in SH-PD rats; B- esophagitis with hyperplastic epithelium, papillary hypertrophy and inflammatory infiltration; C- Specialized Intestinal Metaplasia (Barrett’s Esophagus) with columnar and goblet cells with islands of squamous cells and D- Esophageal Adenocarcinoma with atypia and invasion of lamina propria in EDA-PD rats (Hematoxylin and eosin staining, 200X magnification). Sequential histological changes occurring in EDA-RD group have been published (14).