No abstract

Purpose: Resistance to imatinib mesylate is emerging as a clinical challenge in patients with metastatic gastrointestinal stromal tumors (GIST). Novel patterns of progression have been noted in a number of these patients.The objective of this study was to correlate molecular and radiologic patterns of imitinib-refractory disease with existing conventional criteria for disease progression. Experimental Design: Patients with metastatic GIST treated with imatinib were followed with serial computed tomography/magnetic resonance imaging and [ 18 F]fluoro-2-deoxy-D-glucose positron emission tomography. Where feasible, biopsies were done to document disease progression. Results: A total of 89 patients were followed for a median of 43 months. Forty-eight patients developed progressive disease. A unique ''resistant clonal nodule'' pattern (defined as a new enhancing nodular focus enclosed within a preexisting tumor mass) was seen in 23 of 48 patients and was thought to represent emergence of clones resistant to imatinib. Nodules were demonstrable a median of 5 months (range, 0-13 months) before objective progression defined by tumor size criteria and were the first sign of progression in 18 of 23 patients. Median survival among patients whose first progression was nodular was 35.1months, compared with 44.6 months for patients whose first progression met Southwest Oncology Group criteria (P = 0.31). Comparative tumor biopsies were done in 10 patients at baseline and from progressing nodules. Genotypic analyses of KIT and PDGFRA kinases were done, revealing new activating kinase mutations in 80% (8 of 10) of these patients. Conclusion: The resistant clonal nodule is a unique pattern of disease progression seen in patients with GISTs after an initial response to imatinib and reflects the emergence of imatinibresistant clones. Conventional tumor measurements (Southwest Oncology Group/Response Evaluation Criteria in Solid Tumors) do not detect this subtle finding. A new enhancing nodule growing within a preexisting tumor mass should be classified as a new lesion and be regarded, at least, as partial progression of GIST.

The authors report six patients who had injuries to their common hepatic bile duct at laparoscopic cholecystectomy over a 16-month period. Five of the six complications could be attributed to laser injuries during dissection in the region of Calot's triangle. The authors discuss the possible mechanism of these injuries, their perioperative management, and the methods of surgical reconstruction. The follow-up period ranges from 3 months to 21 months. Liver function parameters and isotope biliary excretion scans are back to normal in all six patients. The potential hazards of laparoscopic surgery demand that extraordinary care be used not only during the actual surgical procedure, but also in the preoperative decision concerning the dissection method to be employed.