Surg Today (2010) 40:287–294 DOI 10.1007/s00595-009-4152-0 Reprint requests to: Y. Kakeji Received: April 27, 2009 / Accepted: June 16, 2009 Review Articles Strategies for Treating Liver Metastasis from Gastric Cancer YOSHIHIRO KAKEJI, MASARU MORITA, and YOSHIHIKO MAEHARA Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan Abstract The prognosis of patients with liver metastasis from gastric cancer is dismal. This article reviews the charac- teristics of gastric cancer metastasizing to the liver, and multimodality of treatments. Differentiated adenocar- cinoma, poorly differentiated adenocarcinoma with a medullary growth pattern, and special types, including endocrine carcinoma and hepatoid carcinoma, are likely to metastasize to the liver. The overexpression of growth factors or adhesion molecules is clinically significant for liver metastasis. Surgery for liver metastases arising from gastric adenocarcinoma is reasonable if a com- plete resection seems feasible after careful preoperative staging. A hepatic resection should always be consid- ered as an option for gastric cancer patients with hepatic metastases. Newer generation cytotoxic agents such as S-1, irinotecan, and taxanes show promising activity for patients with metastases. Adjuvant chemotherapy or molecular targeted therapy will provide significant ben- efits to patients in the future. Key words Gastric cancer · Hepatic resection · Liver metastasis · Adjuvant chemotherapy Introduction Gastric cancer was the fourth most common malignancy in the world in 2007, with an estimated 1 million new cases. 1 It is the second leading cause of cancer death in men and the fourth among women. In Japan, it is second only to lung cancer among deaths due to cancer. 2 As adequate local control is essential for the treatment of gastric cancer, the standard of care for curable gastric cancer in eastern Asia and the United States is either gastrectomy with D2 lymphadenectomy and without postoperative chemoradiation or D0 or D1 gastrectomy with postoperative chemoradiation. 3–7 However, liver metastasis is found in 4%–14% of patients with primary gastric cancer, 8–11 which is often associated with extra- hepatic disease such as peritoneal dissemination, lymph node metastasis, and direct cancer invasion of other organs. Gastric cancer with liver metastasis is a noncur- able, fatal disease with a 5-year survival of less than 10%. This article reviews the characteristics of gastric cancer with liver metastasis and the up-to-date treat- ment of hematogenous metastasis. Characteristics of Gastric Cancer with Liver Metastasis Three histological subtypes of gastric cancer are likely to metastasize to the liver: differentiated adenocarci- noma, poorly differentiated adenocarcinoma, and a special type including endocrine carcinoma and hepa- toid carcinoma. 12–15 The differentiated type grows in a papillary or tubular pattern. The poorly differentiated type exhibits a medullary growth pattern. Gastric hepa- toid adenocarcinoma is histologically similar to hepato- cellular carcinoma. 15 These subtypes have unique characteristics, but share common pathological features such as scant fibrous stroma and abundant tumor blood vessels. 11 The clinicopathological features of gastric cancer with liver metastasis are an expansive pattern of growth, prominent vascular involvement, and a high rate of lymph node metastasis. 16 Some biological characteristics have been reported to be correlated with liver metastasis. The overexpression of growth factors (c-Met, 17 vascular endothelial growth factor [VEGF] 18 ) or adhesion molecules (intercellular adhesion molecule 1 [ICAM-1] 19 or LFA-3 20 ) are clini- cally significant for liver metastasis. The c-Met proto-oncogene encodes the c-Met recep- tor, which is a 190-kDa heterodimeric glycoprotein with