Society for Surgery of the Alimentary Tract
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Cullen F. Roberts*, James N. Luo, Andrei Moscalu, Yingjia Chen, Ali Tavakkoli, Eric G. Sheu
Brigham and Women's Hospital Department of Surgery, Boston, MA

Introduction: Existing human studies have shown conflicting effects of bariatric surgery on colorectal cancer (CRC) risk[1] [2]. These equivocal findings are likely due in part to the heterogeneity of CRC. We have previously found that sleeve gastrectomy (SG) leads to increased colonic tumor growth in a mouse model of colitis-associated cancer, but the effect of SG on genetic CRC syndromes such as Familial Adenomatous Polyposis (FAP) remains unknown. In the murine analogue of FAP, mice with a mutated Adenomatous Polyposis Coli (APC) allele, known as APCMin, develop gastrointestinal (GI) tumors predominantly in the small bowel. Here we examine the effects of SG on tumor formation in APCMin mice.

Methods: Thirty 12-week-old C57BL/6J-APCMin mice were randomized to SG (n=18) or sham (n=12) operation. Five days postoperatively, the mice were begun on a high-fat diet to promote tumor formation. Mice were weighed daily for the first postoperative week and then at three-to-four day intervals until sacrifice 25 days after surgery. At sacrifice, tumors were counted in the colon and proximal, mid, and distal small bowel, and tumor numbers in SG and sham mice were compared using t-tests. Small bowel samples were analyzed for mRNA expression of five cytokines: IL-1b, IL-6, IL-23, IL-33, and TNFa. Additionally, RNA sequencing (RNA-Seq) was performed on colonic tissue to identify transcriptional differences between SG and sham mice.

Results: SG mice developed significantly fewer GI tumors than sham mice (10.9 vs 21.3; p < 0.0001; Figure 1A) with fewer tumors in the mid small bowel (1.7 vs 5.5; p < 0.0001; Figure 1B) and distal small bowel (6.8 vs 12.8; p < 0.01; Figure 1B). TNFa expression was significantly lower in SG mice while IL-1b, IL-6, and IL-23 trended lower. RNA-Seq showed upregulation of 209 genes and downregulation of 107 genes in SG mice compared to sham mice, and transcriptional pathway analysis demonstrated decreased expression of major histocompatibility complex (MHC) class I associated genes in SG mice compared to sham mice.

Conclusions: SG protects against APC-related tumors. SG is associated with a reduction in intestinal inflammatory cytokines and MHC class I pathways, highlighting a potential role of cell-mediated immunity in tumor control after SG.

[1] Bailly L, Fabre R, Pradier C, Iannelli A. Colorectal Cancer Risk Following Bariatric Surgery in a Nationwide Study of French Individuals With Obesity. JAMA Surg. 2020;155(5):395–402. doi:10.1001/jamasurg.2020.0089

[2] Tao, W., Artama, M., von Euler-Chelpin, M., Hull, M., Ljung, R., Lynge, E., Ólafsdóttir, G.H., Pukkala, E., Romundstad, P., Talbäck, M., Tryggvadottir, L. and Lagergren, J. (2020), Colon and rectal cancer risk after bariatric surgery in a multicountry Nordic cohort study. Int. J. Cancer, 147: 728-735.

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