Gastrointestinal Stromal Tumors (GISTs) in Neurofibromatosis Type 1 (NF-1) are typically multifocal, small-bowel-based, and wild-type for KIT and PDGFRA, so surgery remains the cornerstone of treatment. Multifocal duodeno-jejunal involvement poses technical and strategic challenges, and minimally invasive management in this setting is poorly standardized. We describe a hybrid laparoscopic–mini-open, bowel-preserving approach. Laparoscopic access via the Hasson technique with three additional trocars allows systematic small-bowel exploration. Division of the ligament of Treitz and a complete Kocher maneuver fully mobilize the duodeno-pancreatic block. Targeted lesions are exteriorized through a short Alexis-protected minilaparotomy and removed by manual full-thickness wedge resection with double-layer closure. A selective strategy is applied: only enlarging or anatomically critical lesions are resected, while subcentimeter micro-GISTs are left in situ . In a 62-year-old man with NF1 and three growing GISTs (duodenal and jejunal), all targeted lesions were resected with negative (R0) margins. Histology confirmed low-risk and no risk tumors. Recovery was uneventful aside from transient delayed gastric emptying, and the patient was recurrence-free at 12 months. This standardized, reproducible technique provides a tailored minimally invasive option for multifocal NF1-associated GISTs, preserving bowel length without compromising oncologic adequacy.
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