Despite its length and surface area, the small bowel accounts for less than 5% of all gastrointestinal cancers, and has a malignancy rate 50-fold lower than that of the colon.1-3 When tumors do arise in the small bowel, however, they tend to evade detection for some time and therefore commonly present at an advanced stage. This chapter will review the most common types of small bowel neoplasms and their management, including adenocarcinoma, gastrointestinal stromal tumor, and lymphoma, while excluding tumors of the duodenum and neuroendocrine tumors, which are covered elsewhere in this volume.
Background and Epidemiology
For many years adenocarcinoma was the predominant primary neoplasm of the small bowel, but has recently been supplanted by small bowel neuroendocrine tumors.1,3 Excluding the duodenum, adenocarcinoma represents approximately 24% of primary small bowel cancers,1 and has an annual incidence of 2000 to 3000 cases per year in the United States.3 Small bowel adenocarcinoma (SBA) tends to afflict older patients. Surveillance, Epidemiology, and End Results (SEER) program data indicate that more than 85% of SBA patients are older than 50 years, with a median age at diagnosis 67 years.2,3 Due to its rarity, nonspecific symptoms, and lack of screening tools, SBA presents at a later stage than colon cancer. A recent comparison of large bowel with SBA from SEER data found that 32% of SBA presents with stage IV disease, whereas only 20% of colonic adenocarcinomas have metastases at diagnosis.3
Processes causing increased inflammation predispose to SBA. Crohn's disease affecting the small bowel is a strong risk factor for development of SBA, and risk increases with greater duration of symptoms.4 Celiac disease also confers higher risk of SBA.5 Smoking, alcohol use, diets high in animal fats, cystic fibrosis, male gender, and the presence of additional GI cancers have also been correlated with increased SBA risk.2,6,7 Patients with familial polyposis syndromes, such as familial adenomatous polyposis (FAP), hereditary nonpolyposis colorectal cancer (HNPCC), and Peutz–Jeghers syndromes have a high risk of developing small bowel polyps and adenocarcinomas.2
Similar genetic alterations occur in colorectal adenocarcinoma and SBA, with some important differences. Loss of tumor suppressor genes and activating mutations in oncogenes occur in both cancer types, including p53, SMAD4, KRAS, and β-CATENIN.2,7 KRAS mutations were found in 43%, and p53 overexpression in 42% of SBA tumors in one series, similar to rates observed in colorectal adenocarcinomas.8 Interestingly, nonsense mutations in the APC tumor suppressor gene, which occur in 60% to 80% of colorectal adenocarcinomas, are not found in SBA.7 Instead, missense APC mutations are common, occurring in 42% of sporadic SBAs and 7% of celiac-related SBAs.7 Patients with APC...