Bowel perforation associated sunitinib therapy for recurred gastric gastrointestinal stromal tumor
A 78-year-old woman with an abdominal mass for more than 1 month was admitted to Chosun University Hospital. Physical examination revealed a large mass in the periumbilical area. Abdominal computed tomography revealed an 18 cm abdominal mass with extensive central necrosis. She underwent complete resection of the mass, with total gastrectomy, distal pancreatectomy, splenectomy, and transverse colectomy (). Postoperative histopathologic examination showed a gastric GIST with negative resection margins and no metastatic lymph nodes. The mass was a 15 cm × 9 cm gastric GIST with 14 mitoses/50 high-power fields, and was categorized as a high-risk tumor. Immunostaining showed that the tumor was positive for C-KIT and CD34, and negative for S100 expression (). Adjuvant chemotherapy using oral imatinib mesilate was recommended to the patient. However, she declined treatment because it was too expensive.\nEight months after the operation, the patient was found to have recurrent GIST involving the hilum and subcapsular region of the right lobe of the liver and peritoneal nodules. Imatinib (400 mg/day) was started as palliative treatment (). At a 3-month follow-up, the liver masses had decreased and imatinib was found to be well tolerated by the patient, who continued on the same dose of iminitib (). Follow-up imaging 6 months later showed peritoneal seeding in the region of the distal pancreas and a small amount of left pleural effusion and ascites (). The patient refused second-line treatment, and imatinib therapy was continued despite the progression. Two months later, she was admitted because of severe dyspnea due to a large amount of pleural effusion and ascites (). She requested second-line palliative oral medication without undergoing additional diagnostic evaluation.\nBefore she received sunitinib, a complete blood count (CBC) showed the following: white blood cell (WBC) count, 2,990 × 103/µL; neutrophils, 65% (1,943 × 103/µL); hemoglobin, 9.1 g/dL; and platelets, 222 × 103/µL. Partial thromboplastin time (PTT) and activated partial thromboplastin time (aPTT) were in the normal range. The patient's grade I anemia and neutropenia were due to imatinib toxicity. Examination of the pleural effusion revealed the following: WBC, 1,296/m3 (polymorphonuclear cells, 60%); pH, 7.20; lactate dehydrogenase (LDH), 1,266 U/L; and atypical cells. Cultures of the pleural effusate were negative. The results of these laboratory tests suggested malignant pleural effusion.\nThe patient's therapy was changed to oral sunitinib administered at 50 mg/day in cycles consisting of 4 weeks of sunitinib followed by 2 weeks of rest. On day 7 of the first cycle of sunitinib therapy, the volume of the patient's pleural effusion was unchanged, but her dyspnea had improved, and she requested discharge from the hospital. On day 21, sunitinib was found to be well tolerated except for grade I neutropenia (WBC, 2,390 × 103/µL; neutrophils, 1,769 × 103/µL) with markedly decreased pleural effusion and ascites (). Oral sunitinib was continued at 50 mg/day.\nOn day 26 of the first cycle of sunitinib therapy, the patient had a sudden onset of sharp, generalized abdominal pain. An imaging study revealed intraperitoneal free gas with many bubbles near the distal pancreatic region, suggesting small bowel perforation (), and the patient was hospitalized. The admission CBC showed the following: WBC, 1.19 × 103/µL; neutrophils, 63%; hemoglobin, 10.6 g/dL; and platelet count, 89 × 103/µL. The PT and aPTT were 10.9 and 25.6 seconds, respectively. She was diagnosed with generalized peritonitis due to bowel perforation and grade III neutropenia (750 × 103/µL) due to sunitinib toxicity. We recommended emergency surgery; however, the patient's guardian refused consent. The patient expired the next day.