Small Bowel Malignancy

A

Incidence

• 1.

  Although the small intestine comprises 90% of the surface area of the gastrointestinal (GI) tract, less than 3% of primary GI neoplasms occur in this region. Theories for this discrepancy include:

  • a.

    The dilute and liquid contents of the small bowel cause less mucosal irritation.

  • b.

    The rapid transit of intestinal contents provides for shorter exposure to carcinogens.

  • c.

    The lower bacterial load results in less conversion of bile acids into carcinogens by anaerobic organisms.

  • d.

    Carcinogens in food, such as benzpyrene, is degraded to less toxic metabolites by enzyme benzpyrene hydroxylase, which is abundant in the small bowel.

  • e.

    Increased concentration of lymphoid tissue and production of immunoglobulin A (IgA) may have a protective effect.

• 2.

  The majority of tumors are discovered incidentally. Improvements in endoscopy and radiologic techniques have led to an increase in detection rates. Symptoms are often from obstruction, bleeding, intussusception, or metastatic disease.

• 3.

  Incidence increases with:

  • a.

    Male sex

  • b.

    Middle age or older

  • c.

    Consumption of red meat

  • d.

    Ingestion of smoked or cured foods

  • e.

    Prior diagnosis of colon adenocarcinoma

• 4.

  The incidence/detection of carcinoid tumors has increased fourfold in the past 3 decades and is largely responsible for the overall increased incidence of small bowel malignancies.

B

Tumor Characteristics

Carcinoid tumors (44%) are the most common small bowel cancers, followed closely by adenocarcinomas (33%). Lymphomas and sarcomas comprise 8% and 17% of small bowel cancers, respectively ( Table 37.1 ).

• 1.

  Carcinoid tumors

  • a.

    Most common location is the ileum

  • b.

    They are well-differentiated tumors.

  • c.

    They appear as firm intramucosal or submucosal nodules.

  • d.

    Approximately half of carcinoids greater than 2 cm metastasize to the liver.

• 2.

  Adenocarcinoma

  • a.

    Most common location is the duodenum

  • b.

    Risk is elevated in patients with a history of colorectal cancer (see Section I.C).

• 3.

  Primary small bowel lymphoma

  • a.

    Immunoproliferative small intestinal disease (IPSID) (a variant of mucosa-associated lymphoid tissue [MALT])

  • b.

    Enteropathy-associated T-cell lymphoma (EATL), associated with gluten-sensitive enteropathy

• 4.

  Sarcoma

  • a.

    Evenly distributed throughout the small bowel

  • b.

    Most common type: gastrointestinal stromal tumor (GIST)

    • (1)

      Derived from interstitial cell of Cajal

    • (2)

      Positive c-kit (receptor tyrosine kinase) expression, a protooncogene leading to uninhibited cell growth

    • (3)

      Small intestine: second most common site of this tumor

• 5.

  Metastatic lesions

  • a.

    Tumors that tend to spread to the peritoneal cavity are ovarian, colon, and gastric cancers.

  • b.

    Small intestine is the most common site of GI metastases in advanced-stage melanoma.

C

Genetic Predisposition and Pathogenesis

• 1.

  Sporadic tumors

  • a.

    Majority of adenocarcinomas arise from adenomas.

  • b.

    Carcinogenesis pathway is similar to that of colon cancer, with high incidence of tumor-suppressor genes p53 and KRAS mutations.

• 2.

  High-risk inherited syndromes for small bowel adenocarcinoma (see Table 37.1 )

  • a.

    Familial adenomatous polyposis (FAP)

    • (1)

      Autosomal dominant mutation of adenomatous polyposis coli (APC) tumor suppressor gene

    • (2)

      A total of 50%–90% chance of developing duodenal adenomas, with 1 in 20 progressing to malignancy

    • (3)

      Elevated risk of developing desmoid tumors in the small bowel or its mesentery

  • b.

    Peutz-Jeghers syndrome (PJS)

    • (1)

      Autosomal dominant mutation of STK11 tumor suppressor gene

    • (2)

      Manifests with the development of hamartomas throughout the GI tract, which also increase the risk of intussusception

    • (3)

      Elevated risk of small and large bowel adenocarcinomas

    • (4)

      Similar manifestations in juvenile polyposis syndrome (JPS) and Cowden syndrome

  • c.

    Hereditary nonpolyposis colorectal cancer (HNPCC)/Lynch syndrome

    • (1)

      Mutation in DNA mismatch repair genes

    • (2)

      Four percent lifetime risk of small bowel adenocarcinoma

    • (3)

      Responsible for 5%–10% of small bowel adenocarcinomas

    • (4)

      Increased risk of colorectal cancer and endometrial cancer

  • d.

    Multiple endocrine neoplasia type I (MEN1): neuroendocrine tumors of duodenum.

• 3.

  Diseases causing chronic inflammation of the small bowel

  • a.

    Crohn’s disease (CD)

    • (1)

      CD patients have a higher risk (20–30-fold) of small bowel adenocarcinoma than do patients without CD.

    • (2)

      Risk increases with duration of disease and extent of small bowel involvement.

    • (3)

      It commonly presents as a small bowel stricture.

  • b.

    Celiac disease

    • (1)

      Eight percent prevalence of small intestinal adenocarcinoma, with a relative risk of 10 compared with general population.

• 4.

  Immunodeficiency/suppression: increased risk of small bowel lymphoma—for example, in congenital and acquired immunodeficiency states, such as with use of chronic immunosuppressive drugs and celiac disease