Top

Journal of Hepato-Biliary-Pancreatic Sciences

Published in:

01-07-2009 | Original article

Intrahepatic micrometastases around liver metastases from gastric cancer

Authors: Takashi Nomura, Yukinori Kamio, Naoki Takasu, Toshiyuki Moriya, Akiko Takeshita, Masaomi Mizutani, Osamu Hachiya, Ichiro Hirai, Wataru Kimura

Published in: Journal of Hepato-Biliary-Pancreatic Sciences | Issue 4/2009

Abstract

Background/Purpose

We aimed to clarify the association between the presence of micrometastases around liver metastases from gastric cancer and the results of hepatic resection. In addition, we investigated the influence of E-cadherin and matrix metalloproteinase (MMP)-7 expression on the development of micrometastases.

Methods

Micrometastases around liver metastases were examined microscopically in 31 metastatic liver tumor specimens resected from 17 patients who had undergone hepatic resection for liver metastases from gastric cancer. E-cadherin and MMP-7 expression in the primary gastric tumor, the liver metastases, and the micrometastases were examined immunohistochemically.

Results

Hepatic micrometastases were present in around 48% of the liver metastases, accounting for 59% of the patients. The tumor recurrence rate in the remnant liver after hepatic resection was significantly higher, and survival significantly poorer, in patients with such micrometastases than in those without. Micrometastases tended to appear around the liver metastases that had reduced E-cadherin expression. Most of the micrometastases in the lymph ducts and sinusoids showed reduced E-cadherin expression. MMP-7 expression was not correlated with the presence of micrometastases.

Conclusions

About half of the hepatic metastases from gastric cancer had seeded off micrometastases, and the presence of these micrometastases was associated with a poorer result of hepatic resection. Reduced E-cadherin expression in metastatic liver tumors may be associated with the development of micrometastases.

Okano K, Maeba T, Ishimura K, Karasawa Y, Goda F, Wakabayashi H, et al. Hepatic resection for metastatic tumors from gastric cancer. Ann Surg. 2002;235:86–91.PubMedCrossRef

Sakamoto Y, Ohyama S, Yamamoto J, Yamada K, Seki M, Ohta K, et al. Surgical resection of liver metastases of gastric cancer: an analysis of a 17-year experience with 22 patients. Surgery. 2003;133:507–11.PubMedCrossRef

Miyazaki M, Itoh H, Nakagawa K, Ambiru S, Shimizu H, Togawa A, et al. Hepatic resection of liver metastases from gastric carcinoma. Am J Gastroenterol. 1997;92:490–3.PubMed

Shi M, Zhang CQ, Zhang YQ, Liang XM, Li JQ. Micrometastases of solitary hepatocellular carcinoma and appropriate resection margin. World J Surg. 2004;28:376–81.PubMedCrossRef

Kokudo N, Miki Y, Sugai S, Yanagisawa A, Kato Y, Sakamoto Y, et al. Genetic and histological assessment of surgical margins in resected liver metastases from colorectal carcinoma: minimum surgical margins for successful resection. Arch Surg. 2002;137:833–40.PubMedCrossRef

Japanese Gastric Cancer Association. Japanese classification of gastric carcinoma. 2nd English ed. Gastric Cancer 1998;1:10–24.

Sugano H, Nakamura K, Kato Y. Pathological studies of human gastric cancer. Acta Pathol Jpn. 1982;32(Suppl 2):329–47.PubMed

Poon RT, Fan ST, Ng IO, Lo CM, Liu CL, Wong J. Different risk factors and prognosis for early and late intrahepatic recurrence after resection of hepatocellular carcinoma. Cancer. 2000;89:500–7.PubMedCrossRef

Nakashima O, Kojiro M. Recurrence of hepatocellular carcinoma: multicentric occurrence or intrahepatic metastasis? A viewpoint in terms of pathology. J Hepatobiliary Pancreat Surg. 2001;8:404–9.PubMedCrossRef

10.

Kato T, Yasui K, Hirai T, Kanemitsu Y, Mori T, Sugihara K, et al. Therapeutic results for hepatic metastasis of colorectal cancer with special reference to effectiveness of hepatectomy: analysis of prognostic factors for 763 cases recorded at 18 institutions. Dis Colon Rectum. 2003;46:S22–31.PubMed

11.

Belli G, D’Agostino A, Ciciliano F, Fantini C, Russolillo N, Belli A. Liver resection for hepatic metastases: 15 years of experience. J Hepatobiliary Pancreat Surg. 2002;9:607–13.PubMedCrossRef

12.

Nakamura S, Suzuki S, Konno H. Resection of hepatic metastases of colorectal carcinoma: 20 years’ experience. J Hepatobiliary Pancreat Surg. 1999;6:16–22.PubMedCrossRef

13.

Nanko M, Shimada H, Yamaoka H, Tanaka K, Masui H, Matsuo K, et al. Micrometastatic colorectal cancer lesions in the liver. Surg Today. 1998;28:707–13.PubMedCrossRef

14.

Yokoyama N, Shirai Y, Ajioka Y, Nagakura S, Suda T, Hatakeyama K. Immunohistochemically detected hepatic micrometastases predict a high risk of intrahepatic recurrence after resection of colorectal carcinoma liver metastases. Cancer. 2002;94:1642–7.PubMedCrossRef

15.

Imamura H, Matsuyama Y, Shimada R, Kubota M, Nakayama A, Kobayashi A, et al. A study of factors influencing prognosis after resection of hepatic metastases from colorectal and gastric carcinoma. Am J Gastroenterol. 2001;96:3178–84.PubMedCrossRef

16.

Isono T, Miyazaki M, Udagawa I, Koshikawa H, Iinuma K, Itoh H, et al. The clinicopathological study of intrahepatic micrometastases in hepatic metastatic carcinioma: comparison between hepatic metastasis of gastric cancer and of colorectal cancer. J Jpn Soc Cancer Ther. 1992;27:893–9.

17.

Ambiru S, Miyazaki M, Ito H, Nakagawa K, Shimizu H, Yoshidome H, et al. Benefits and limits of hepatic resection for gastric metastases. Am J Surg. 2001;181:279–83.PubMedCrossRef

18.

Mayer B, Johnson JP, Leitl F, Jauch KW, Heiss MM, Schildberg FW, et al. E-cadherin expression in primary and metastatic gastric cancer: down-regulation correlates with cellular dedifferentiation and glandular disintegration. Cancer Res. 1993;53:1690–5.PubMed

19.

Gabbert HE, Mueller W, Schneiders A, Meier S, Moll R, Birchmeier W, et al. Prognostic value of E-cadherin expression in 413 gastric carcinomas. Int J Cancer. 1996;69:184–9.PubMedCrossRef

20.

Lee KH, Shin SJ, Kim KO, Kim MK, Hyun MS, Kim TN, et al. Relationship between E-cadherin, matrix metalloproteinase-7 gene expression and clinicopathological features in gastric carcinoma. Oncol Rep. 2006;16:823–30.PubMed

21.

Zheng HC, Sun JM, Li XH, Yang XF, Zhang YC, Xin Y. Role of PTEN and MMP-7 expression in growth, invasion, metastasis and angiogenesis of gastric carcinoma. Pathol Int. 2003;53:659–66.PubMedCrossRef

22.

Ougolkov A, Yamashita K, Bilim V, Takahashi Y, Mai M, Minamoto T. Abnormal expression of E-cadherin, beta-catenin, and c-erbB-2 in advanced gastric cancer: its association with liver metastasis. Int J Colorectal Dis. 2003;18:160–6.PubMed

23.

Yonemura Y, Endou Y, Kimura K, Fushida S, Bandou E, Taniguchi K, et al. Inverse expression of S100A4 and E-cadherin is associated with metastatic potential in gastric cancer. Clin Cancer Res. 2000;6:4234–42.PubMed

24.

Yonemura Y, Endou Y, Fujita H, Fushida S, Bandou E, Taniguchi K, et al. Role of MMP-7 in the formation of peritoneal dissemination in gastric cancer. Gastric Cancer. 2000;3:63–70.PubMedCrossRef

25.

Inayoshi J, Ichida T, Sugitani S, Tsuboi Y, Genda T, Honma N, et al. Gross appearance of hepatocellular carcinoma reflects E-cadherin expression and risk of early recurrence after surgical treatment. J Gastroenterol Hepatol. 2003;18:673–7.PubMedCrossRef

26.

Gao ZH, Tretiakova MS, Liu WH, Gong C, Farris PD, Hart J. Association of E-cadherin, matrix metalloproteinases, and tissue inhibitors of metalloproteinases with the progression and metastasis of hepatocellular carcinoma. Mod Pathol. 2006;19:533–40.PubMedCrossRef

27.

Ishii Y, Nakasato Y, Kobayashi S, Yamazaki Y, Aoki T. A study on angiogenesis-related matrix metalloproteinase networks in primary hepatocellular carcinoma. J Exp Clin Cancer Res. 2003;22:461–70.PubMed

28.

Nanashinma A, Yamaguchi H, Sawai T, Yasutake T, Tsuiji T, Jibiki E. Expression of adhesion molecules in hepatic metastases of colorectal carcinoma: relationships to primary tumors and prognosis after hepatic resection. J Gastroenterol Hepatol. 1999;14:1004–9.CrossRef

29.

Zeng ZS, Shu WP, Cohen AM, Guillem JG. Matrix metalloproteinase-7 expression in colorectal cancer liver metastases: evidence for involvement of MMP-7 activation in human cancer metastases. Clin Cancer Res. 2002;8:144–8.PubMed

Title: Intrahepatic micrometastases around liver metastases from gastric cancer
Authors: Takashi Nomura
Yukinori Kamio
Naoki Takasu
Toshiyuki Moriya
Akiko Takeshita
Masaomi Mizutani
Osamu Hachiya
Ichiro Hirai
Wataru Kimura
Publication date: 01-07-2009
Publisher: Springer Japan
Published in: Journal of Hepato-Biliary-Pancreatic Sciences / Issue 4/2009
Print ISSN: 1868-6974
Electronic ISSN: 1868-6982
DOI: https://doi.org/10.1007/s00534-009-0081-y

At a glance: The STEP trials

Springer Medicine

Intrahepatic micrometastases around liver metastases from gastric cancer

Abstract

Background/Purpose

Methods

Results

Conclusions

At a glance: The STEP trials

Springer Medicine

Abstract

Background/Purpose

Methods

Results

Conclusions

Please log in to get access to this content

Other articles of this Issue 4/2009

Techniques for performing laparoscopic liver resection in various hepatic locations

Laparoscopic liver resection: a systematic review

Estimation of indocyanine green elimination rate constant k and retention rate at 15 min using patient age, weight, bilirubin, and albumin

Hepatocellular carcinoma with extensive peliotic change

Usefulness of the CLIP scoring system for prediction of postoperative prognosis of patients with large hepatocellular carcinoma

Laparoscopic liver resection: how far can we go?