Gastrointestinal stromal tumors (GISTs) represent the most common mesenchymal 
neoplasms of the GI tract. The optimal management of GISTs has been evolving 
rapidly over the past 5 years and depends on proper histopathologic and 
radiologic diagnosis as well as appropriate multidisciplinary medical and 
surgical treatments. Complete surgical resection of primary localized GIST with 
negative margins remains the best therapeutic option today. In the setting of 
locally advanced or metastatic disease, imatinib mesylate has emerged as the 
initial treatment of choice, administered either as cytoreductive or as 
definitive treatment. Surgery or ablative modalities in this setting are 
becoming increasingly employed, particularly when all disease becomes amenable 
to gross resection or destruction, or to manage complications arising from the 
disease following imatinib failure. We report on the surgical management of an 
unusual and clinically significant complication following progression of disease 
secondary to imatinib resistance. The role of surgical therapy in the management 
of GIST complications following resistance to imatinib and the integration of 
surgical and molecular therapy of locally advanced or metastatic GISTs are 
discussed.