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Selective approaches to gastric cancer patients with liver metastases: role of liver-directed chemotherapy
Sir Metastasis is the hallmark of disease progression and treatment failure in gastric carcinoma patients. peritoneal cavity and liver are the major sites of treatment failure following gastric resection i. The overall incidence of liver metastasis in gastric carcinoma patients is 2540% 2. Multifocality and frequent recurrence of the disease preclude an enthusiastic approach to treat this disease by hepatic resection. Data from 75 patients treated between 1980 and 1998 for liver metastasis from gastric carcinoma were analysed retrospectively. patient-, tumour- and treatment-related parameters were evaluated in terms of patient survival and a comprehensive treatment guideline was prepared. Out of 75 patients, 15 (20.0%) underwent resection and systemic chemotherapy when a curative resection was anticipated, 13 underwent hepatic arterial infusion chemotherapy (HAIC) mitomycin C + adriamycin + 5-fluorouracil) due to the non-curative primary resections or extensive liver involvement, 33 patients received only systemic chemotherapy due to advanced disease and in 14 patients definitive treatment could not be offered for miscellaneous reasons. A significant number of patients in the HAIC group had peritoneal involvement p=O.OOOl), multiple metastatic tumours in the liver (p=O.O009) and synchronous disease (p=O.OOOl) compared with the resected group. The longest survival encountered was 30 months (mean 7.6 months). Among the several prognostic factors, patients with no peritoneal involvement (pcO.O348), small metastatic tumour size (~~0.0365) and single tumour (p
selected patients with metachronous disease and a single metastatic lesion. It is intriguing that patients with HAIC treatment had almost the same l-yr (50.8% vs 46.7%) and even a better 2-yr (9.1’% vs 6.7%) survival when compared with those who had had hepatic resection and adjuvant therapy, although the patients with HAIC had more unfavourable prognostic factors and were not offered hepatic resection. Likewise, Okuyama et al. ’ reported HAIC treatment to be highly effective and, in our study, HAIC was the strongest independent prognostic indicator in the multivariate analysis. Although this is the largest retrospective study to-date on this topic, a prospective study would, nonetheless be worthwhile in gastric carcinoma patients.
Sir The role of apoptosis in the maintenance of a correct balance between cell proliferation and death is well known. For this reason, studies of the phenomenon have being increasingly performed in various diseases in order to clarify some pathophysiological mechanisms i. In Crohn’s disease, whilst it is well known that reduced apoptosis of lymphocytes is involved in maintaining mucosal inflammation ‘, very few data are available concerning the possible changes of this process in the intestinal epithelium despite hyperproliferation which occurs in this site. Recently, Di
Sabatino et al. reported, not only confirmation of prolonged mucosal lymphocyte survival, but also an increase in epithelial apoptosis in the intestinal mucosa of patients with Crohn’s disease. Apoptotic cells have been evaluated by the traditional TUNEL method which reveals DNA fragmentation 3. The data in that report, published as yet only as an abstract, agree very closely with recent results of ours confirming the increase of apoptosis in the intestinal epithelium even if evaluated by a less standardised method i.e., immunohistochemical detection of 85kDa caspase cleaved fragment (~85) of human poly (ADP-ribose) polymerase (PARP), which reveals the blockade
ILK. Dher, Ii. Kubota, A. Yamanoi, T. Ono, H. Yoshimura, S. Ohno, M. Tachibana, Ii. Kohno, N. Nagasue The Second Department of Surgery, Shimane Medical University, lzumo 693 - 8501, Japan. fax: +81-853-202229. E-mail: [email protected]. jp
’ Maruyama K, Gkabayashi K, Kinoshita T. Progress in gastric cancer surgery in Japan and its limits of radicality. World J Surg 1987;11:418-25. ’ Averbach AM, Jacquet P. Strategies to decreasethe incidence of intra-abdominal recurrence in resectable gastric cancer. Br J Surg 1996;83:726-33.
j Bines SD, England G, Deziel J, Witt TR, Doolas A, Roseman D. Synchronous, metachronous, and multiple hepatic resections of liver ttmors originating from primary gastric tumors. Surgery 1993;114:799-805. ’ Okuyama K, Isono K, Juan IK, Onoda S, Ochiai T, Yamamoto Y, et al. Evaluation of treatment for gastric cancer with liver metastasis. Cancer 1985;55:2498-505.
selected patients with metachronous disease and a single metastatic lesion. It is intriguing that patients with HAIC treatment had almost the same l-yr (50.8% vs 46.7%) and even a better 2-yr (9.1’% vs 6.7%) survival when compared with those who had had hepatic resection and adjuvant therapy, although the patients with HAIC had more unfavourable prognostic factors and were not offered hepatic resection. Likewise, Okuyama et al. ’ reported HAIC treatment to be highly effective and, in our study, HAIC was the strongest independent prognostic indicator in the multivariate analysis. Although this is the largest retrospective study to-date on this topic, a prospective study would, nonetheless be worthwhile in gastric carcinoma patients.
Sir The role of apoptosis in the maintenance of a correct balance between cell proliferation and death is well known. For this reason, studies of the phenomenon have being increasingly performed in various diseases in order to clarify some pathophysiological mechanisms i. In Crohn’s disease, whilst it is well known that reduced apoptosis of lymphocytes is involved in maintaining mucosal inflammation ‘, very few data are available concerning the possible changes of this process in the intestinal epithelium despite hyperproliferation which occurs in this site. Recently, Di
Sabatino et al. reported, not only confirmation of prolonged mucosal lymphocyte survival, but also an increase in epithelial apoptosis in the intestinal mucosa of patients with Crohn’s disease. Apoptotic cells have been evaluated by the traditional TUNEL method which reveals DNA fragmentation 3. The data in that report, published as yet only as an abstract, agree very closely with recent results of ours confirming the increase of apoptosis in the intestinal epithelium even if evaluated by a less standardised method i.e., immunohistochemical detection of 85kDa caspase cleaved fragment (~85) of human poly (ADP-ribose) polymerase (PARP), which reveals the blockade
ILK. Dher, Ii. Kubota, A. Yamanoi, T. Ono, H. Yoshimura, S. Ohno, M. Tachibana, Ii. Kohno, N. Nagasue The Second Department of Surgery, Shimane Medical University, lzumo 693 - 8501, Japan. fax: +81-853-202229. E-mail: [email protected]. jp
’ Maruyama K, Gkabayashi K, Kinoshita T. Progress in gastric cancer surgery in Japan and its limits of radicality. World J Surg 1987;11:418-25. ’ Averbach AM, Jacquet P. Strategies to decreasethe incidence of intra-abdominal recurrence in resectable gastric cancer. Br J Surg 1996;83:726-33.
j Bines SD, England G, Deziel J, Witt TR, Doolas A, Roseman D. Synchronous, metachronous, and multiple hepatic resections of liver ttmors originating from primary gastric tumors. Surgery 1993;114:799-805. ’ Okuyama K, Isono K, Juan IK, Onoda S, Ochiai T, Yamamoto Y, et al. Evaluation of treatment for gastric cancer with liver metastasis. Cancer 1985;55:2498-505.