RESUMEN
Interventional therapy in necrotizing pancreatitis is evolving. Efforts to modify or prevent pancreatic necrosis by intra-arterial infusion of antibiotics and antiproteases have been described. Moreover, traditional approaches to the surgical management of infected pancreatic necrosis are being challenged by a host of endoscopic and percutaneous techniques. While these approaches are potentially valuable additions to interventional therapy in necrotizing pancreatitis, few evidence-based studies are available to support their supplanting more traditional approaches at this time. Cooperative evidence-based multiinstitutional studies will be required to address the validity of these proposals.
Asunto(s)
Pancreatitis Aguda Necrotizante/terapia , Antibacterianos/administración & dosificación , Medicina Basada en la Evidencia , Infusiones Intraarteriales , Pancreatitis Aguda Necrotizante/tratamiento farmacológico , Pancreatitis Aguda Necrotizante/cirugía , Péptido Hidrolasas/administración & dosificaciónRESUMEN
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 35.1 months, 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 imatinib-resistant 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.
Asunto(s)
Antineoplásicos/uso terapéutico , Resistencia a Antineoplásicos , Tumores del Estroma Gastrointestinal/tratamiento farmacológico , Tumores del Estroma Gastrointestinal/patología , Piperazinas/uso terapéutico , Pirimidinas/uso terapéutico , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Benzamidas , Células Clonales/patología , Resistencia a Antineoplásicos/genética , Evolución Molecular , Femenino , Tumores del Estroma Gastrointestinal/diagnóstico por imagen , Humanos , Mesilato de Imatinib , Masculino , Persona de Mediana Edad , Proteínas Proto-Oncogénicas c-kit/genética , Radiografía , Receptor alfa de Factor de Crecimiento Derivado de Plaquetas/genética , Eliminación de Secuencia , Análisis de SupervivenciaRESUMEN
Radiologically guided interventional procedures in the liver have continually increased, in number and variety, over the years. Factors promoting these advances include new technology, innovative ideas, and growing acceptance by clinicians and patients. Percutaneous biopsy and drainage procedures are firmly established techniques with low complication rates. Ablation by injected substances is useful for treating certain tumor types. The most exciting development is the introduction of percutaneous thermal techniques for tumor ablation. Although more experience is needed to optimize the use of focal thermal ablation, early results seem promising.