Advanced Gastric Cancer Associated with Disseminated Intravascular Coagulation Successfully Treated with 5-fluorouracil and Oxaliplatin
The 63-year-old man was admitted to the hospital on 24 November 2010 with epigastric pain, diffuse back pain and melena. The physical examination showed poor general condition (Eastern Cooperative Oncology Group performance grade 3) and petechia in lower extremities. He had blood pressure of 140/80 mmHg, pulse rate of 100 beats/min, respiratory rate of 22 beats/min, body temperature of 36.6℃ and oxygen saturation of 95% in room air upon admission. There was no anemia of conjunctiva or jaundice of sclera and both neck and chest were normal. The blood count showed hemoglobin of 12.1 g/dl, leukocytes of 6,900/mm3 and platelet count of 24,000/mm3. Liver function tests showed total protein of 6.6 g/dl, albumin of 4.0 g/dl, total bilirubin of 1.6 mg/dl, aspartate aminotransferase (AST) of 268 IU/L, alanine aminotransferase (ALT) of 36 IU/L and alkaline phosphatase of 214 IU/L. Blood coagulation tests revealed prolonged prothrombin time (PT 1.53 international normalized ratio, 56%), elevated fibrinogen degradation products level (FDP 66.5 µg/ml), D-dimer (21.27 µg/ml) and lactate dehydrogenase level (LDH 2,116 IU/L). HBsAg and hepatitis C virus antibody showed negative findings. Upper gastrointestinal endoscopy performed in our hospital found a Bormann type 2 mass in the lower body. Because there was bleeding on a vessel exposed to the area of mass, argon plasma coagulation was performed (). Endoscopic biopsy results were poorly differentiated adenocarcinoma. Abdominal computed tomography scanning revealed gastric cancer in the lower body and multiple metastases in neighboring lymph nodes, and abdominal lymph nodes were observed. Liver and bilateral adrenal metastases were observed but there was no evidence of cirrhotic change. We could exclude other primary liver diseases. Positron emission tomography scanning found an increase in uptake of fluorodeoxyglucose in gastric area. Liver, bilateral adrenal and multiple bone metastases were observed as well (). We diagnosed stage IV gastric cancer having multiple bone metastases complicated by DIC. Gastric tumor bleeding was not controlled after three repeated procedures using gastrofiberscopic intervention with argon plasma coagulation. Repeated packed red blood cell (RBC), fresh frozen plasma and platelet concentrate transfusions, DIC with pancytopenia resulted in more aggravated. With consent of the patient and his family, we performed 5-fluorouracil (5-FU) and oxaliplatin combination chemotherapy on 1 December 2010 to control the underlying gastric cancer. Systemic combination chemotherapy was composed of 5-FU 750 mg/m2 on day 1, 2 and day 22, 23, oxaliplatin 75 mg/m2 and leucovorin 75 mg/m2 on day 1 and day 22. Chemotherapy was repeated every four weeks. After one cycle of the 5-FU and oxaliplatin therapy, the bleeding symptoms improved, and the DIC process was successfully controlled. At that time, the hematologic profile improved but did not resolve to normal: white blood cell 4,800/mm3, hemoglobin 12.0 g/dl, platelet 117,000/mm3. Liver function tests showed total protein of 7.7 g/dl, albumin of 4.1 g/dl, total bilirubin of 0.8 mg/dl, AST of 35 IU/L, ALT of 32 IU/L and alkaline phosphatase of 316 IU/L. He felt better than before chemotherapy, melena stopped and the petechiae of lower extremities disappeared. His back pain, previously uncontrolled by high dose opioid administration, dramatically improved after chemotherapy.\nChemotherapy was treated 6 times in a total of 6 months. Traced abdominal computed tomography scanning, positron emission tomography scanning and upper gastrointestinal endoscopy () showed complete remission of gastric cancer, lymph nodes and metastases areas ().\nAfter 8 cycles of initial combination therapy, although we recommended continuing chemotherapy until progression, he refused further chemotherapy. Thereafter, we observed him without systemic chemotherapy at regular follow up 3 week intervals. During the observation period he did not showed abnormal hematologic profile and back pain and there was no evidence of progression in abdominal computed tomography scan and follow up gastrofiberscopy. After 4 months of observation, he suffered severe back pain without hematologic abnormality. In the positron emission tomography-computed tomography (PET-CT) scan, aggravated multiple spine lesions were detected (). We performed 5-FU, leucovorin and irinotecan combination chemotherapy on 3 December 2011 to control the metastatic lesion. Systemic combination chemotherapy was composed of 5-FU 1,000 mg/m2 on day 1, 2 and day 22, 23, leucovorin 200 mg/m2 on day 1 and day 22, irinotecan 180 mg/m2 on day 1 and day 22. Chemotherapy was repeated every four weeks. During the 2nd line chemotherapy, laboratory tests revealed no evidence of DIC. After 4 cycles of second line chemotherapy, follow up PET-CT scan showed multiple spine lesions improved (). But after 6 cycles of second line chemotherapy, PET-CT scan showed that multiple bone metastases and both adrenal metastases were aggravated (). We performed tegafur+gemeracil+oteracil potassium (TS-1), cisplatin combination chemotherapy on 8 August 2012 to control the metastatic lesion. Systemic combination chemotherapy was composed of TS-1 60 mg for two weeks, cisplatin 75 mg/m2 on day 1, every 3 weeks. The blood count showed hemoglobin of 10.9 g/dl, leukocytes of 3,100/mm3 and platelet count of 115,000/mm3. Liver function tests showed total protein of 6.1 g/dl, albumin of 3.3 g/dl, total bilirubin of 0.8 mg/dl, AST of 56 IU/L, ALT of 25 IU/L and alkaline phosphatase of 611 IU/L. He remains free of DIC up to the present time. In the course of chemotherapy he did not experience febrile neutropenia or overt systemic infection. He is now treated with 3rd cycle of TS-1 and cisplatin without complications.