Small Bowel Adenocarcinoma

Small bowel adenocarcinoma is a rare epithelial malignancy arising most commonly in the duodenum, followed by jejunum and ileum. Predisposing conditions include Crohn disease, coeliac disease, Lynch syndrome, familial adenomatous polyposis and Peutz Jeghers syndrome.

Curative treatment depends on complete surgical resection with adequate regional lymph node assessment. Node positive disease has a substantially worse prognosis and generally requires adjuvant chemotherapy.

Symptoms depend on site.

Jejunal and ileal disease commonly presents with intermittent obstruction, abdominal pain, anaemia, occult bleeding or weight loss.

Duodenal disease may produce vomiting, jaundice or gastric outlet symptoms depending on location.

An adult with unexplained recurrent small bowel obstruction without previous surgery should be investigated for a structural lesion, including malignancy.

CT enterography or contrast CT: define the primary lesion, regional lymphadenopathy and distant metastases.

Upper endoscopy or enteroscopy: obtain tissue when the lesion is endoscopically accessible.

Mismatch repair or microsatellite instability testing should be performed because it has prognostic and therapeutic implications.

Regional nodal staging is important. N1 disease means one or two positive regional nodes and N2 disease means three or more.

Surgery

Resectable jejunal or ileal adenocarcinoma requires segmental small bowel resection with en bloc regional mesenteric lymphadenectomy.

A tumour involving the terminal ileum or ileocaecal valve usually requires ileocaecal resection or right hemicolectomy with appropriate nodal clearance.

Duodenal cancers involving the second portion or ampullary region commonly require pancreaticoduodenectomy. Selected proximal first portion or distal third and fourth portion tumours may undergo segmental duodenal resection when an oncologically adequate margin and nodal dissection can be achieved.

Adjuvant treatment

Stage I disease is generally observed after complete resection.

Node positive stage III disease should receive approximately 6 months of adjuvant fluoropyrimidine based chemotherapy, preferably an oxaliplatin containing doublet in a fit patient. High risk stage II disease may also justify adjuvant treatment, particularly with T4 disease, perforation, inadequate nodal harvest, poor differentiation, lymphovascular invasion or positive or close margins.

A standard modified FOLFOX6 regimen every 14 days is:

• Oxaliplatin 85 mg/m² IV day 1
• Leucovorin 400 mg/m² IV day 1
• Fluorouracil 400 mg/m² IV bolus day 1
• Fluorouracil 2400 mg/m² continuous IV infusion over 46 hours

An alternative CAPOX regimen every 21 days is:

• Oxaliplatin 130 mg/m² IV day 1
• Capecitabine 1000 mg/m² orally twice daily on days 1 to 14

Dose reduction is required for clinically significant renal impairment with capecitabine and for relevant treatment toxicity.

Metastatic disease

FOLFOX or CAPOX is a common first line approach for fit patients.

Test metastatic disease for mismatch repair deficiency or microsatellite instability. For MSI high or mismatch repair deficient advanced disease, immune checkpoint therapy is an important option.

A commonly used pembrolizumab regimen is:

Pembrolizumab 200 mg IV every 3 weeks or 400 mg IV every 6 weeks.

Obstruction from unresectable disease may require bypass or palliative resection when systemic therapy cannot restore gastrointestinal continuity quickly enough.