Small bowel adenocarcinoma

Small bowel adenocarcinoma is a rare malignancy of the gastrointestinal tract that most commonly occurs in the duodenum. The median age at diagnosis is 66 years. Risk factors include heavy alcohol use, smoking, certain medical conditions (e.g., IBD, celiac disease), and familial cancer syndromes (e.g., Lynch syndrome). The clinical presentation is often nonspecific; symptoms include intermittent crampy abdominal pain, nausea, vomiting, gastrointestinal bleeding, and weight loss. Diagnosis requires a biopsy, which is typically obtained via endoscopy, and is supported by laboratory studies and cross-sectional imaging. Management for localized disease is primarily surgical resection, often followed by adjuvant chemotherapy based on the stage and molecular features. For unresectable or metastatic disease, treatment involves systemic therapy; the specific regimen is chosen based on mismatch repair or microsatellite instability status.

• Incidence: 2.6 per 100,000 men and 2.0 per 100,000 women ^[1]
• Median age at diagnosis: 66 years ^[1]
• Anatomic distribution ^[2]
  • Duodenum: ∼ 50% of cases
  • Jejunum: ∼ 30% of cases
  • Ileum: ∼ 20% of cases

Epidemiological data refers to the US, unless otherwise specified.

• Lifestyle factors ^[1]
  • Heavy alcohol use
  • Smoking
  • Dietary factors (e.g., low fiber intake, high intake of red and/or processed meat)
• Associated medical conditions
  • Inflammatory bowel disease ^[1]
  • Celiac disease ^[1]
• Familial syndromes ^[1]
  • Lynch syndrome
  • Peutz-Jeghers syndrome
  • Familial adenomatous polyposis

The clinical presentation is often nonspecific. ^[1][2]

• Crampy, intermittent abdominal pain (most common)
• Nausea and vomiting
• Occult gastrointestinal bleeding and/or clinical features of anemia
• Weight loss
• Jaundice
• Symptoms of gastric outlet obstruction or bowel obstruction (depending on tumor location)

Approach ^[1]

• Obtain baseline laboratory studies and cross-sectional imaging.
• Consult gastroenterology for endoscopic evaluation and biopsy of suspected lesions.
• Obtain enterography or capsule studies if the initial workup is inconclusive.
• The diagnosis is confirmed on histopathology.

The diagnosis of small bowel adenocarcinoma is often delayed due to nonspecific symptoms. ^[3]

Laboratory studies ^[1]

• CBC: Evaluate for anemia due to occult bleeding.
• CMP: Assess for hepatic or metabolic abnormalities suggesting metastases.
• Tumor markers: CA 19-9 and CEA to support the diagnosis and monitor treatment response

Endoscopy ^[1]

• EGD ± EUS
  • For visualization, staging, and to obtain biopsy samples
  • Universal mismatch repair or microsatellite instability testing is recommended for all patients with small bowel adenocarcinoma.
• Double-balloon endoscopy: Useful for evaluating mid-to-distal small bowel strictures or lesions not accessible by standard endoscopy.
• Capsule endoscopy: Consider if a lesion is not identified on other imaging studies.

Imaging ^[1]

• CT or MRI: first line to assess for local invasion and distant metastasis
• CT or MR enterography or enteroclysis if standard imaging is inconclusive
• PET-CT scan: not routinely indicated; may help clarify equivocal CT or MRI findings

• Adhesions
• Inflammatory bowel disease
• Irritable bowel syndrome
• Diverticulitis
• Adenomas
• Polyposis syndromes
• Other small bowel neoplasms
• Peptic ulcer disease

The differential diagnoses listed here are not exhaustive.

General principles ^[1][3]

• Treatment plans should be developed and overseen by a multidisciplinary team (e.g., medical oncology, surgical oncology, palliative care).
• Surgical resection with lymphadenectomy is the cornerstone of management for localized disease.
• Systemic therapy is based on stage and molecular features.
• Neoadjuvant or palliative approaches are used for unresectable or metastatic disease.

Localized resectable disease (stage I–III) ^[1][3]

• Surgery: segmental resection with en bloc lymphadenectomy
  • Duodenal tumors: pancreaticoduodenectomy or segmental duodenal resection
  • Jejunal or ileal tumors: segmentectomy
• Adjuvant therapy (based on stage and mismatch repair or microsatellite instability status)
  • Stage I: observation
  • Stage II: observation or chemotherapy (e.g., FOLFOX, CAPEOX, 5-FU/LV, or capecitabine)
  • Stage III: chemotherapy (e.g., FOLFOX, CAPEOX, 5-FU/LV, or capecitabine)

Locally unresectable or medically inoperable disease ^[1][3]

• Neoadjuvant therapy may be used to achieve resectability.
• Diversion or stenting for obstruction and palliative chemotherapy if unresectable

Distant metastatic disease (stage IV) ^[1][3]

• Metastasectomy may be considered for patients with limited visceral metastases.
• Unresectable peritoneal metastases: palliative systemic therapy (e.g., FOLFOX, CAPEOX, or FOLFOXIRI, ± bevacizumab)

Posttreatment surveillance ^[1]

• Comprehensive clinical examination
• Measurement of CEA and/or CA 19-9 levels
• CT chest, abdomen, and pelvis