39-14: Malignancies of the Small Intestine

The frequency of different tumor types varies by location within the small intestine. Adenocarcinomas are most common in the duodenum and jejunum and neuroendocrine tumors, in the ileum. Lymphomas and sarcomas each have similar incidences in the various segments of the small intestine.

1. SMALL INTESTINAL ADENOCARCINOMAS

These cancers often present with abdominal pain and nausea. They are rare, with 11,790 new diagnoses estimated for 2022 in the United States. Adenocarcinomas are most often diagnosed at stage III or IV, but their prognosis is slightly worse than for similar stage colon adenocarcinoma. The duodenum is the most common site of small bowel adenocarcinoma, specifically the periampullary region. The incidence of ampullary carcinoma is increased more than 200-fold in patients with familial adenomatous polyposis. Periodic endoscopic surveillance to detect early ampullary neoplasms is therefore recommended. Ampullary carcinomas may present with GI bleeding or jaundice due to bile duct obstruction. Surgical resection of early lesions is curative in up to 40% of patients. Although ampullary adenocarcinomas may be of either intestinal or pancreatic ductal origin, adjuvant chemotherapy with a pancreatic regimen is typically recommended and is associated with improved overall survival compared with observation alone.

Most cases of nonampullary adenocarcinomas present with symptoms of obstruction, acute or chronic GI bleeding, or weight loss. Resection is recommended for control of symptoms. For localized disease, the role of (neo)adjuvant chemotherapy is under investigation. The benefit of adjuvant therapy after resection of stage II or III tumors is unclear, but it is generally administered using chemotherapy agents active in colorectal cancer. For advanced/unresectable disease, first-line doublet chemotherapy is standard. It is uncertain whether extending treatment to triplet chemotherapy brings added benefit. Two trials suggest value from adding bevacizumab to chemotherapy. Pembrolizumab is an accepted treatment modality for mismatch repair-deficient tumors; more trials with immunotherapy are underway.

Patients with Crohn disease have an increased risk of small intestinal adenocarcinoma, most commonly in the ileum; it may be difficult to distinguish preoperatively from disease-related fibrous stricture. Small bowel adenocarcinoma in young patients or those with a family history of GI or extracolonic adenocarcinomas should prompt screening for the Lynch syndrome. In this syndrome, there is an increased risk of small bowel adenocarcinomas, occurring in approximately 4–8% of affected patients. According to NCCN guidelines, periodic surveillance with esophagogastroduodenoscopy (EGD) and extended duodenoscopy or capsule endoscopy may be considered for patients with Lynch syndrome, although there are no randomized trials to support such small bowel screening.