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Blog aimed at residents in surgery
 URL :  www.surgical-oncology.net             e mail surgoncnet@gmail.com
Treatment of gastric liver metastases: second updating.

Romeo Giuli MD, resident.
School of General and Emergency Surgery.
University of Siena.   Italy.



March 2003.     Review Article

To previous article about gastric liver metastases
To the first updating


Sakamoto et al found 5% of the 4730 patients who underwent gastrectomy for gastric cancer at their institution between 1985 and 2001 developed liver metastases develop synchronously or metachronously, but only 10% of them underwent hepatic resection. This small population of patients is discussed in their study.
The number of liver metastases was a significant prognostic factor for survival after hepatectomy in patients with metastasis of primary gastric cancer according to a univariate and a multivariate analysis. The favorable survival outcome for patients with a solitary metastasis indicates that patients with a solitary metastasis of gastric cancer are good candidates for surgical resection.
Regarding the timing of hepatectomy, their series showed no significant difference in survival between synchronous and metachronous metastasis. Thus, synchronous liver metastasis from gastric cancer is not necessarily a contraindication for attempts at curative resective therapy of both the primary site (stomach) and the metastatic site (liver). Ochiai et al also reported 4 / 5-year survivors, 3 of whom had synchronous metastases ( 1, 2 ).
On the contrary Ambiru et al reported significantly longer survival in patients with metachronous metastasis (5-year survival, 29%) than in those with synchronous disease (5-year survival, 6%), and other authors have also reported favorable outcomes in patients with metachronous metastasis ( 3, 4, 5 ).
The clinicopathologic factors of primary gastric cancer may influence survival after hepatectomy, but the impact of these factors was not significant in the Sakamoto study. Ochiai et al reported that pathologic factors associated with the primary tumor, such as serosal, lymphatic, and venous invasion, were significant prognostic factors of survival. However, most authors have reported that these factors are not useful for the prognosis of patients with primary gastric carcinoma. ( 1, 2, 3, 4, 6 )
In the Sakamooto series, neither the surgical margin nor the procedure of the liver resection influenced the survival outcome.Their present policy for treatment of metastases of gastric carcinoma is a limited nonanatomic resection of the liver metastasis ( 1 ).
A maximum tumor diameter of less than 5 cm was a significant prognostic factor of survival according to the multivariate analysis, although the size of the metastatic tumor did not appear to influence patient survivals in other reports ( 1, 3, 4 ).
Repeat hepatic resections were performed in 4 patients with favorable outcomes. The clinical significance of repeat hepatectomies for gastric metastasis has rarely been discussed ( 1, 2, 4, 7 ).

In the Zacherl study primary tumor localization within the proximal third of the stomach and bilobar liver involvement appear to be predictive of poor outcome. On the other hand,curative resection of metachronous liver metastases may allow long-term survival in selected patients ( 8 ).

According to Saiura et al. study even though it is rare, a survival time of 5-years can be achieved by resection of gastric cancer metastatic to the liver. Their results suggest that a patient with liver metastasis from gastric cancer has a greater chance of surviving long-term if there is no lymph node metastasis at the primary site ( 9 ).

The findings of Kunieda study indicate the importance of treating patients with hepatic metastases from gastric cancers with a combination of surgical resection and HAI chemotherapy. Gastrectomy and incomplete liver resection for cancer reduction, even in patients with multiple hepatic metastases, may have beneficial effects if postoperative HAI chemotherapy is given. To date, there have been no reports describing an analysis of large numbers of patients. Therefore, prospective controlled randomized multiple center trials should be conducted to obtain further evidence of the benefits of hepatectomy and chemotherapy for gastric cancer patients with liver metastases ( 14 ).
The effectiveness of repeated hepatic dearterialization (RHD) therapy was evaluated in 26 patients with unresectable primary and secondary liver tumors by Kimoto et al study.
RHD was performed in 12 patients with hepatocellular carcinoma (HCC), 7 with hepatic metastases from colorectal carcinoma, and 7 with hepatic metastases from gastric carcinoma. It was repeatedly carried out by occluding the hepatic artery for 1 h twice daily. All patients concurrently received an intra-arterial infusion of anticancer drugs. More than 50% remission of the hepatic tumors, defined as a partial response (PR), was demonstrated in 8 patients (31%). A higher PR was seen in hepatic tumors from metastatic gastric cancer (5 out of 7 patients; 71%). Most patients who suffered severe complications had HCC with liver cirrhosis.These preliminary results suggest that RHD with intra-arterial chemotherapy is an acceptable palliative treatment for patients with unresectable liver metastasis from gastric cancer; however, the majority of patients with HCC are not responsive to such treatment, primarily because most have underlying cirrhosis predisposing to the development of postoperative complications at an unacceptably high rate ( 20 ).

Marrelli et al. found liver metastases in 13.5% of their 208 patients who had undergone curative resection for gastric cancer; in most cases the diagnosis was made within 2 years after surgical treatment. Preoperative positivity for serum tumor markers, lymph node involvement, and intestinal histotype proved to be the most important risk factors associated with hepatic recurrence. Postoperative measurement of serum tumor markers may be useful for an early diagnosis of liver metastases during followup ( 21 ).
Soichi Tomimatsu et al. suggest that the immunohistochemical expression of IL-1 alpha is a useful predictor of liver recurrence in patients undergoing a curative resection for gastric carcinoma with subserosal invasion. Interleukin - 1 has been reported to augment the hematogenous metastasis of some cancers by inducing the expression of adhesion molecules on vascular endothelial cells and also increasing the expression of the proteases from tumor cells in vitro ( 23 ).

References

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2) Ochiai T, Sasako M et al. Hepatic resection for metastatic tumours from gastric cancer : analysis of prognostic factors. Br J Surg 1994; 81:1175-8. Pub Med

3) Satoshi Ambiru, Masaru Miyazaki et al. Benefits and limits of hepatic resection for gastric metastases. The American Journal of Surgery 181 (2001) 279-283. Pub Med

4) Keiichi Okano et al. Hepatic resection for metastatic tumors from gastric cancer. Annals of Surgery 2002, vol 235, n1, 86-91. Pub Med

5) Imamura H et al. A study of factors influencing prognosis after resection of hepatic metastases from colorectal and gastric carcinoma. Am J Gastroenterology 2001; 96:3178-3184. Pub Med

6) Miyazaki M, Itho 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. Pub Med

7) Morise Z, Yamafuji K, Takahashi T, Asami A, Takeshima K, Hayashi N, et al. Successful treatment of recurrent liver metastases from gastric cancer by repeated hepatic resections: report of a case. Surg Today 2000;30:1041-5. Pub Med

8) Johannes Zacherl et al.A Analysis of Hepatic Resection of Metastasis Originating From Gastric Adenocarcinoma. J Gastrointestinal Surg 2002;6:682 -689. Pub Med

9) Saiura A, Umekita N, Inoue S, Maeshiro T et al. Clinicopathological features and outcome of hepatic resection for liver metastasis from gastric cancer. Hepatogastroenterology. 2002 Jul-Aug;49(46):1062-5. Pub Med

10) Blumgart LH,Allison DJ.Resection and embolisation in the management of secondary hepatic tumors.World J Surg 1982;6:32 -45. Pub Med

11) Lindell G,Ohlsson B,Saarela A,Andersson R,Tranberg KG.Liver resection of noncolorectal secondaries.J Surg Oncol 1998;69:66 -70. Pub Med

12) E Linhares et al. Major hepatectomy for isolated metastases from gastric adenocarcinoma. HPB 2003; Vol 5, number 4: 235-237.

13) Foster JH et al. Survival after liver resection for secondary tumors. Am J Surg 1978; 135: 389-94. Pub Med

14) Katsuyuki Kunieda et al. Evaluation of Treatment for Synchronous Hepatic Metastases from Gastric Cancer with Special Reference to Long-Term Survivors. Surg Today (2002) 32:587-593. Pub Med

15) Morrow CE, Grage TB, Sutherland DER, Najarian JS. Hepatic resection for secondary neoplasms. Surgery 1982;92:610-4.

16) Wolf RF, Goodnight JE, Krag DE, Schneider PD. Results of resection and proposed guidelines for patient selection in instances of noncolorectal hepatic metastases. Surg Gynecol Obstet 1991;173:454-60. Pub Med

17) 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. Pub Med

18) Yonemura Y, Matuki N, Sakuma H, Katayama K, Sawa T, Fujimura T, et al. Effect of intra-hepatoarterial infusion of MMC and CDDP for gastric cancer patients with liver metastases. Surg Today 1992;22:253-9. Pub Med

19) Kumada Y, Arai Y, Ito K, Takayasu Y, Nakamura K, Ariyoshi Y, et al. The Japanese hepatic arterial infusion study group: phase II study of combined administration of 5-fluorouracil, epirubicin and mitomycin-C by hepatic artery infusion in patients with liver metastases of gastric cancer. Oncology 1999;57:216-23. Pub Med

20) Takeo Kimoto, Akira Yamanoi et al. Repeated Hepatic Dearterialization for Unresectable Carcinomas of the Liver: Report of a 10-Year Experience. Surg Today (2001) 31:984-990. Pub Med

21) Daniele Marrelli, Franco Rovello et al. Risk Factors for Liver Metastases After CurativeSurgical Procedures for Gastric Cancer: A Prospective Study of 208 Patients Treated with Surgical Resection. J Am Coll Surg 2004;198:51-58. Pub Med

22) Ikeda Y, Mori M, Kajiyama K, et al. Indicative value of carcino-embryonic antigen (CEA) for liver recurrence following curative resection of stage II and III gastric cancer. Hepato-Gastroenterology. 1996;43:1281-1287. Pub Med

23) Soichi Tomimatsu et al. Significant correlation between expression of interleukin-1 alpha and liver metastases in gastric cancer. Cancer 2001; 91: 1272-6. Pub Med



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