Management of Small Bowel Gastrointestinal Stromal Tumors (GISTs)

Complete surgical resection (R0) without lymph node dissection is the standard treatment for small bowel GISTs ≥2 cm. 1

Initial Assessment and Diagnosis

Imaging studies:
- Contrast-enhanced CT scan of abdomen and pelvis is the investigation of choice for diagnosis and staging 2, 1
- MRI may be used as an alternative when CT is contraindicated 2
- PET scan can help differentiate active tumor from necrotic tissue and clarify ambiguous findings 2
Biopsy:
- EUS-guided fine-needle aspiration is preferred for histological diagnosis 1
- Pathological diagnosis relies on CD117 (KIT) and/or DOG1 positivity 1, 3
- Mutational analysis of KIT and PDGFRA is essential for confirming diagnosis and guiding treatment 1

Resectable disease:
- Complete surgical resection (R0) without lymph node dissection is the standard treatment 2, 1
- Segmental resection of small intestine is appropriate for small bowel GISTs 1
- Resection should be accomplished with minimal morbidity; complex multivisceral resection should be avoided 2
Surgical approach:
- Laparoscopic approach is safe for smaller tumors (≤5 cm) 1
- Laparoscopic or laparoscopic-assisted resections are associated with low recurrence rates, short hospital stay, and low morbidity 2
- Important principles: complete macroscopic resection, preservation of pseudocapsule, and avoidance of tumor rupture 2
- Resection specimen should be removed in a plastic bag to avoid spillage 2
Marginally resectable tumors:
- Consider preoperative imatinib for:
  - Marginally resectable tumors
  - Cases where surgical morbidity would be improved by reducing tumor size
  - Large tumors likely to require multivisceral resection 1
- Close monitoring is essential as some patients may become unresectable rapidly 2

Risk stratification factors:
- Tumor size
- Mitotic rate
- Tumor location (small intestinal GISTs show worse prognosis than gastric GISTs) 2
- Tumor rupture (significantly worsens prognosis) 1
Adjuvant therapy:
- Adjuvant imatinib for 3 years is recommended for high-risk patients after complete resection 2, 1
- High-risk features include: large tumor size, high mitotic rate, non-gastric location, and tumor rupture 1
- Mutational analysis is critical for adjuvant therapy decisions:
  - PDGFRA D842V-mutated GISTs should not receive adjuvant therapy due to lack of sensitivity 2
  - Higher dose of imatinib (800 mg daily) may be considered for KIT exon 9 mutations 2

Regular imaging surveillance based on risk stratification:
- Higher-risk patients require more intensive follow-up 1
- CT abdomen and pelvis with contrast is the method of choice 1
- First follow-up within 6 months, then more relaxed if stable 1

Unresectable or metastatic disease:
- Imatinib mesylate is the standard first-line therapy (400 mg daily) 1, 4
- For KIT exon 9 mutations, higher dose (800 mg daily) may be more effective 1
- Treatment should continue indefinitely until disease progression or unacceptable toxicity 1
Second-line therapy:
- Sunitinib for KIT exon 9,13, and 14 mutations 5
- Regorafenib for highly refractory tumors 6, 5
- Ponatinib for exon 17 mutations 5

Emergency presentations:
- Small bowel GISTs may present with acute abdomen, obstruction, perforation, rupture, or peritonitis 7
- Gastrointestinal bleeding is the most common emergency presentation 7
- Emergency surgery follows acute abdomen management guidelines 8
Pitfalls to avoid:
- Tumor rupture during surgery significantly worsens prognosis and increases risk of peritoneal relapse 1
- Lymph node dissection is not necessary for GISTs as lymphatic spread is rare 1
- Palliative resection of GISTs is not advocated unless for emergency indications 8
- Delaying mutational analysis can lead to inappropriate adjuvant therapy decisions 1

By following these guidelines, the management of small bowel GISTs can be optimized to improve patient outcomes and survival.