Five-Year Survival of Alpha-Fetoprotein-Producing Gastric Cancer with Synchronous Liver Metastasis: A Case Report
A 69-year-old man with upper abdominal pain was referred to our hospital in August 2006 by a local physician. Upper gastrointestinal endoscopy revealed a Borrmann type II-like tumor in the posterior wall of the lower part of the stomach (). The biopsy specimen revealed well-differentiated adenocarcinoma, and immunohistological staining showed that tumor cells were positive for alpha-fetoprotein-producing (AFP). An upper gastrointestinal series radiography showed an elevated lesion with a central depression () in the lower part of the stomach. Laboratory examination revealed mildly elevated levels of aspartate aminotransferase (AST 67 IU/L), lactate dehydrogenase (834 IU/L), and alkaline phosphatase (565 IU/L). Serum level of carcinoembryonic antigen and CA19-9 was normal, but that of AFP was markedly increased (160,000 ng/ml).\nAbdominal contrast-enhanced computed tomography (CECT) revealed a 14 cm long hypovascular tumor in the left lobe of the liver (). On the basis of these findings, we diagnosed AFPGC with synchronous liver metastasis.\nOur initial treatment plan was to perform a distal gastrectomy and an extended left lobectomy of the liver. However, another liver metastasis was found in the right lobe of the liver by the intraoperative sonography. We limited the surgery to distal gastrectomy with D2 lymph node dissection and Billroth I reconstruction in August 2006. The resected specimen was determined to be a 2.8 cm long Borrmann type II-like tumor ().\nHistopathological examination of the gastric tumor revealed a well-differentiated adenocarcinoma with neoplastic growth of hepatocyte-like cells (). The level of invasion was submucosal and 3 of 35 dissected lymph nodes were positive for metastasis. Intraoperative biopsy of the liver tumor showed features similar to those of the gastric tumor (). Immunohistological staining showed that tumor cells in both the gastric tumor () and the biopsy specimen from the liver tumor () were positive for AFP.\nAfter surgery, we placed a catheter into the proper hepatic artery for HIA. Chemotherapy using oral tegafur/gimeracil/oteracil potassium (TS-1, Taiho Co. Ltd., Tokyo, Japan) (120 mg/body/day from days 1 to 21)/HIA-cisplatin (CDDP) (30 mg/body/day on days 8 and 21, every 28 days) was started at day 15 after the surgery. After 4 courses, CECT revealed that the size of the metastatic tumor in the left lobe had decreased to 53.6% of the peak (), and the small liver metastasis had disappeared. The serum AFP level had decreased to 2,910 ng/ml.\nSix months after the surgery, the serum level of AFP began to increase, that is why we performed a left lobectomy. The resected specimen showed atrophic change in the left lobe and an odd-shaped soft liver tumor (). On cut sections, the tumor was yellowish and highly denatured (). Microscopic findings revealed degenerative changes and necrosis in almost all sections of the tumor. Viable cells were similar in structure to the microscopic findings of the primary gastric cancer. After liver resection, 9 courses of adjuvant oral TS-1/HIA-CDDP and oral TS-1/CPT-11 by drip infusion of vein (div) were administered.\nTwenty-five months after the first surgery, we performed a partial lung resection because of new metastasis to the lung (). Four months after partial lung resection, radiotherapy was performed to treat 2 new lung metastases. We obtained complete response transiently, but another new lung metastasis and para-aortic lymph node metastases appeared immediately. To treat these metastatic lesions, we performed chemotherapy sequentially as follows: 6 courses of paclitaxel (PTX) (div); 2 courses of 5'-Doxifluridine (DFUR) (oral)/Docetaxel (DOC) (div)/CDDP (div); 5 courses of DFUR (oral)/DOC (div); 8 courses of intravenous injection of 5-fluorouracil (5FU)/Adriamycin/Mitomycin-C (FAM); 2 courses of TS-1 (oral)/CPT-11 (div); and 6 courses of PTX (div) ().\nIn spite of these combination chemotherapies, metastatic lesions became difficult to control at 54 months after the first surgery, and the serum AFP level rose to 84,434 ng/ml. Liver metastases () and mediastinal lymph node metastasis enlarged gradually (). The patient complained of respiratory distress resulting from bronchial oppression by enlarged lymph nodes. We could not use trastuzumab because immunohistochemical analysis revealed that human epidermal growth factor receptor type 2 was not expressed in either the primary lesion or the metastatic liver tumor. We proposed best supportive care, but the patient wanted to try a molecular-targeted drug. The administration of oral sorafenib tosylate (sorafenib) was begun at a dose of 800 mg/body/day using of a private import. After 2 months, his serum level of AFP dropped from 100,000 to 59,198 ng/ml. CECT revealed marked attenuation of vascularity at the liver metastasis, but a decrease in tumor size was not observed (). The mediastinal lymph nodes shrunk in size by 16.2% (). The patient's respiratory distress was completely alleviated, and stable disease was observed for a period of 4 months. The only adverse events observed were grade 1 hoarseness, increased AST, and hand-foot syndrome. The patient eventually died from cancer cachexia at 60 months after the first surgery.