Is a total gastrectomy and splenectomy recommended for a large Gastrointestinal Stromal Tumor (GIST)?

Total Gastrectomy and Splenectomy for Large GIST

For large gastric GISTs, total gastrectomy should be avoided whenever possible, and splenectomy should only be performed if there is direct tumor invasion of the spleen or splenic hilum lymph nodes—neoadjuvant imatinib therapy should be strongly considered first to downstage the tumor and enable less morbid, function-sparing surgery. 1

Surgical Principles for Large Gastric GISTs

Primary Goal: Organ Preservation

• The goal of GIST surgery is R0 resection (complete removal with negative margins) while preserving as much organ function as possible 1, 2
• Segmental gastric resection or wedge resection is the preferred approach for gastric GISTs, even when large, as long as a 1-2 cm macroscopic margin can be achieved 1
• Total gastrectomy is considered "potentially morbid surgery" and should be avoided unless absolutely necessary for oncologic clearance 1

When Total Gastrectomy May Be Required

• Total gastrectomy is only indicated when the tumor location or size makes it impossible to achieve adequate margins with partial gastrectomy 1
• For tumors located along the greater curvature of the fundus or corpus where adequate surgical margins cannot be obtained with partial resection, total gastrectomy may be necessary 1
• If pancreatic or splenic invasion requires pancreaticosplenectomy, total gastrectomy becomes necessary regardless of tumor location 1

Splenectomy Considerations

Evidence Against Routine Splenectomy

• Splenectomy is generally associated with increased postoperative complications without survival benefit 1, 3, 4
• A landmark randomized controlled trial (JCOG0110) with 505 patients demonstrated that spleen preservation was non-inferior to splenectomy for proximal gastric tumors, with 5-year survival of 76.4% versus 75.1% respectively (hazard ratio 0.88) 4
• Meta-analysis of randomized trials showed splenectomy increased overall morbidity (OR 2.11, p<0.001) without improving survival 3

Specific Indications for Splenectomy in GIST

• Splenectomy should only be performed for GISTs when there is direct tumor invasion of the spleen or macroscopic involvement of splenic hilum lymph nodes (station 10) 1
• For tumors located along the greater curvature with suspected involvement of station 4sa or 10 lymph nodes, splenectomy may be indicated 1
• Note: Lymph node dissection is generally unnecessary for GISTs as lymphatic spread is rare (except in SDH-deficient GISTs) 1, 2

Neoadjuvant Therapy Strategy

Critical Approach for Large or Complex GISTs

• For larger, more complex tumors that may require multi-visceral resection or total gastrectomy, it is essential to obtain a pre-operative diagnosis and consider neoadjuvant imatinib to downstage the tumor 1
• This approach enables less mutilating and function-sparing surgery, potentially avoiding total gastrectomy altogether 1
• Mutational analysis is mandatory before starting neoadjuvant therapy to exclude imatinib-resistant disease (particularly PDGFRA D842V mutations) 1

Neoadjuvant Protocol

• Pre-treatment with imatinib is recommended when R0 surgery is not feasible or could be achieved through less mutilating surgery after cytoreduction 1
• Standard dose is 400 mg daily, with 800 mg daily for KIT exon 9 mutations 1, 2
• Maximal tumor response typically occurs after 6-12 months, at which point surgery should be performed 1
• Early tumor response assessment is mandatory using functional imaging (PET-CT) within a few weeks to avoid delaying surgery in non-responding disease 1

Surgical Technique Considerations

Laparoscopic Approach

• Laparoscopic partial gastrectomy may be considered for large gastric GISTs in favorable anatomic locations by expert surgeons 1, 5
• A retrospective study of 30 patients with mean tumor size 9.5 cm (range 5-17 cm) showed laparoscopic partial gastrectomy was feasible with mean operative time 152.67 minutes and mean hospital stay 3.53 days 5
• Laparoscopic approach is strongly discouraged for voluminous tumors requiring total gastrectomy or when complete resection without capsule rupture cannot be ensured 1

Intraoperative Principles

• Avoid direct tumor handling and use plastic bags for specimen removal to prevent tumor seeding 2
• Tumor resection must be carefully performed to avoid tumor rupture, which significantly increases peritoneal recurrence risk 1, 2
• Peritoneal and hepatic surfaces should be carefully examined during laparotomy to rule out tumor spread 1

Post-Operative Management

Adjuvant Therapy

• Adjuvant imatinib for 3 years is standard treatment for high-risk GISTs 1
• Large GISTs (>10 cm) are automatically classified as high-risk regardless of mitotic count 1
• If tumor rupture occurs during surgery, adjuvant imatinib is mandatory with consideration for lifelong treatment 2

Common Pitfalls to Avoid

• Do not perform total gastrectomy reflexively for large GISTs—always consider neoadjuvant imatinib first to enable organ-sparing surgery 1
• Do not perform splenectomy unless there is direct splenic invasion—the morbidity is significant without oncologic benefit 3, 4
• Do not proceed with extensive surgery without obtaining tissue diagnosis and mutational analysis, as this guides both neoadjuvant and adjuvant therapy decisions 1
• Do not perform lymphadenectomy routinely for GISTs, as lymphatic spread is rare (exception: SDH-deficient GISTs) 1, 2
• Avoid aggressive multi-visceral resection when neoadjuvant therapy could achieve the same oncologic outcome with less morbidity 1