Sections View Full Chapter Figures Tables Videos Annotate Full Chapter Figures Tables Videos Supplementary Content + Download Section PDF Listen ++ For further information, see CMDT Part 39-14: Malignancies of the Small Intestine + Key Features Download Section PDF Listen +++ +++ Essentials of Diagnosis ++ Acute gastrointestinal (GI) bleeding with hematochezia or melena Chronic GI blood loss resulting in fatigue and iron deficiency anemia Obstruction resulting in vomiting +++ General Considerations ++ Adenocarcinoma occurs most commonly in the duodenum Ampullary carcinoma incidence is increased > 200-fold in patients with familial adenomatous polyposis Nonampullary adenocarcinoma of the small intestine: majority have metastasized at the time of diagnosis Lymphoma may arise primarily in the GI tract or involve it secondarily in disseminated disease In the United States, primary GI lymphoma accounts for 5% of all lymphomas and 20% of small bowel malignancies Most common histologic subtype is non-Hodgkin extranodal marginal zone (MALT) B cell lymphoma Enteropathy-associated T cell lymphoma (EATL) Appears to be increasing in incidence in the United States Is associated with the diagnosis of celiac disease In the Middle East, lymphoma occurs in immunoproliferative small intestinal disease Carcinoid tumors account for one-third of small intestinal tumors Carcinoid tumors derive from neuroendocrine cells and may or may not secrete a number of hormones, including serotonin or its precursors Most are malignant, though many behave in an indolent fashion Even small carcinoid tumors may metastasize, usually by extension to the local lymph nodes and to the liver Carcinoid syndrome occurs in < 10% of patients, usually in patients with hepatic metastasis; caused by tumor secretion of hormonal mediators Most malignant sarcomas arise from stromal tumors that stain positive for CD117; Kaposi sarcoma is rare except in untreated AIDS Most benign small bowel polyps occur singly; multiple polyps suggest a hereditary polyposis syndrome Small bowel adenocarcinoma in young patients or those with a family history of gastrointestinal adenocarcinomas should prompt screening for Lynch syndrome (hereditary nonpolyposis colorectal cancer syndrome) + Clinical Findings Download Section PDF Listen +++ +++ Symptoms and Signs ++ Most small bowel cancers have already metastasized at the time of diagnosis Adenocarcinomas Abdominal pain Nausea Nonampullary adenocarcinoma of the small intestine Obstruction Acute or chronic bleeding Weight loss Ampullary carcinoma Jaundice due to common bile duct obstruction Bleeding Primary lymphoma Abdominal pain Weight loss Nausea and vomiting Abdominal distention Anemia Occult blood in the stool Carcinoid tumors Most asymptomatic Carcinoids are generally indolent tumors that spread slowly May present with intermittent abdominal pain, bowel obstruction, or bowel infarction Manifestations of carcinoid syndrome: facial flushing, edema of the head and neck (especially with bronchial carcinoid), abdominal cramps and diarrhea, bronchospasm, cardiac lesions (pulmonary or tricuspid stenosis or regurgitation), and telangiectases Neuroendocrine tumors Diarrhea Flushing Wheezing +++ Differential Diagnosis ++ Crohn disease +++ Benign polyps ++ Mucosal polyps: adenoma, hamartoma, hyperplastic Lipoma Benign stromal tumor (leiomyoma) +++ Malignant lesions ++ Adenocarcinoma Lymphoma (primary or secondary) Carcinoid Malignant stromal tumor (sarcoma) Kaposi sarcoma + Diagnosis Download Section PDF Listen +++ +++ Laboratory Tests ++ Alpha heavy chains in the serum in 70% of patients with lymphoma occurring in immunoproliferative small intestinal disease Hypoalbuminemia secondary to protein-losing enteropathy in lymphoma Serum chromogranin A is elevated in most neuroendocrine tumors, although its sensitivity for small, localized carcinoid tumors is unknown Urinary 5-hydroxyindoleacetic acid > 25 mg/24 h and serum serotonin elevated in advanced (usually metastatic) carcinoid tumors +++ Imaging Studies ++ Video capsule endoscopy, CT or MR enterography or barium small bowel series usually identify small bowel tumors Imaging and possibly bone marrow biopsy help determine tumor stage Somatostatin receptor scintigraphy (OctreoScan) or gallium Ga-68 DOTATATE PET scan are routinely used in staging and can help identify disease that may benefit from treatment with somatostatin analogs +++ Diagnostic Procedures ++ Enteroscopy to visualize and biopsy small intestinal tumors Endoscopic, percutaneous, or laparoscopic biopsy establishes the diagnosis of primary intestinal lymphoma Bone marrow biopsy and, in some cases, lymphangiography for staging of primary lymphoma Proctoscopy: rectal carcinoids usually detected incidentally as submucosal nodules (most often < 1 cm in size) Appendectomy: appendiceal carcinoids < 2 cm in size are identified in 0.3% + Treatment Download Section PDF Listen +++ +++ Medications ++ Role of adjuvant chemotherapy in adenocarcinoma is unclear; if administered, chemotherapy agents active in colorectal cancer are used Systemic chemotherapy with or without radiation therapy for primary lymphoma with extensive disease Octreotide Inhibits hormone secretion from carcinoid tumors Can be administered subcutaneously three times a day or a long-acting intramuscular depot formulation can be administered once monthly Provides dramatic relief of symptoms in 90% of patients with carcinoid syndrome for a median period of 1 year Conventional cytotoxic chemotherapy agents do not achieve significant responses in carcinoid tumors and have not been associated with improved outcomes Long-acting somatostatin analog Cornerstone of therapy for patients who are symptomatic either from tumor bulk or carcinoid syndrome In 90% of patients, this results in dramatic relief of symptoms of carcinoid syndrome, including diarrhea or flushing, for a median period of 1 year Thereafter, many patients stop responding to octreotide Options to disease progression include octreotide dose escalation or addition of everolimus +++ Surgery ++ Surgical or endoscopic excision of symptomatic benign tumors is recommended Surgical resection of ampullary carcinoma is curative in up to 40% Curative or palliative resection of nonampullary adenocarcinoma Curative resection of primary intestinal lymphoma for stage IE disease Locoregional radiation should be considered if surgical margins are positive Excision of carcinoids of small intestine, appendix, rectum if < 2 cm in size and if evidence of lymphatic spread Advanced small intestinal carcinoid disease In selected patients with hepatic-dominant disease, resection of hepatic metastases may provide dramatic improvement in carcinoid syndrome symptoms Tumor debulking with liver-directed therapy (chemoembolization or radioembolization) may also provide symptomatic improvement More extensive cancer resection operation is warranted for carcinoid tumors > 2 cm in size since they are associated with metastasis in > 20% of appendiceal and ~10% of rectal carcinoids Resection of hepatic metastases for refractory carcinoid syndrome, diarrhea +++ Therapeutic Procedures ++ Liver-directed therapy (chemoembolization, radioembolization or surgical debulking) may provide symptomatic improvement in some patients with hepatic metastases + Outcome Download Section PDF Listen +++ +++ Follow-Up ++ Periodic endoscopic surveillance to detect early ampullary neoplasms +++ Complications ++ Cardiac right-sided valvular lesions are a late manifestation of metastatic carcinoid tumors +++ Prognosis ++ Adenocarcinoma Overall, prognosis is slightly worse than for similar stage colon adenocarcinoma Carcinoid tumors Five-year survival rates for patients with stage I and II disease are 96% and 87%, respectively For resectable disease with lymph node involvement (stage III), 5-year disease-free survival is 74% However, by 25 years, < 25% of patients are disease-free + References Download Section PDF Listen +++ + +Alwers E et al. Associations between molecular classifications of colorectal cancer and patient survival: a systematic review. Clin Gastroenterol Hepatol. 2019 Feb;17(3):402–10. [PubMed: 29306042] + +Elli L et al. Use of enterosocopy for the detection of malignant and premalignant lesions of the small bowel in complicated celiac disease: a meta-analysis. Gastrointest Endosc. 2017 Aug;86(2):264–73. [PubMed: 28433612] + +Kim JS et al. Imaging and screening of cancer of the small bowel. Radiol Clin North Am. 2017 Nov;55(6):1273–91. [PubMed: 289915661] + +Lee MR et al. Incidence trends of gastroenteropancreatic neuroendocrine tumors in the United States. Clin Gastroenterol Hepatol. 2019 Oct;17(11):2212–7. [PubMed: 30580091] + +National Cancer Institute. SEER Cancer Stat Facts: Small Intestine Cancer, 2020. https://seer.cancer.gov/statfacts/html/smint.html + +National Comprehensive Cancer Network. Clinical Practice Guidelines in Oncology. Neuroendocrine and adrenal tumors. Version 2.2020. https://www.nccn.org/professionals/physician_gls/pdf/neuroendocrine.pdf + +Ngamruengphong S et al. Prevalence of metastasis and survival of 788 patients with T1 rectal carcinoid tumors. Gastrointest Endosc. 2019 Mar;89(3):602–6. [PubMed: 30447216] + +Puccini A et al. Management of advanced small bowel cancer. Curr Treat Options Oncol. 2018 Nov 5;19(12):69. [PubMed: 30397729] + +Rondonotti E et al. Neoplastic diseases of the small bowel. Gastrointest Endosc Clin N Am. 2017 Jan;27(1):93–112. [PubMed: 27908521]