Elsevier

Journal of Hepatology

Volume 36, Issue 6, June 2002, Pages 774-779
Journal of Hepatology

Microwave coagulation therapy accelerates growth of cancer in rat liver

https://doi.org/10.1016/S0168-8278(02)00058-2Get rights and content

Abstract

Background/Aims: Although microwave coagulation therapy (MCT) has been performed for liver cancer, there has been no report examining the influence of this therapy on the growth of possible remnant cancer.

Methods: A solid cube of AH-130 cells (ascites hepatoma cell line) was implanted into the left lateral lobe of the rat liver. Five days later, MCT was applied to the middle liver lobe of these rats. Tumor growth and cytokine levels in plasma and the liver were compared between rats that underwent MCT and rats that did not.

Results: The mean tumor weight in the MCT group (222.6±51.5 mg, mean±SD) was significantly greater than that in the control group (126.7±19.7 mg, P<0.01) at postoperative day (POD) 5. Immunohistochemistry for anti-proliferating cell nuclear antigen showed the labeling index in the MCT group (90.4%) to be higher than that in the control group (76.7%, P<0.01). Liver basic fibroblast growth factor and transforming growth factor-beta 1 levels in the MCT group on POD 3 were significantly higher than levels in the control group.

Conclusions: The present study suggests the clinically important finding that MCT accelerates the growth of small residual tumors in the liver.

Introduction

Microwave coagulation therapy (MCT), in which an electrode is inserted directly into the target tumor, is, like laser-induced thermotherapy [1] and radio-frequency ablation (RFA) [2], a local ablation therapy. Microwaves of 2450 MHz, which are generated between the tip and base of the electrode, cause heat-coagulation of the surrounding tissue [3]. MCT is applicable to many cancers, including hepatocellular carcinoma (HCC) [4], [5], metastatic liver cancer from digestive tract malignancies, and prostatic cancer [6], as well as benign tumors. For the treatment of liver cancer, MCT is well suited because it provides substantial local control of the tumor. In histopathological studies of post-MCT liver, necrotic change was observed around the site of heat-coagulation [7], [8], [9]. Another advantage is that MCT is applicable in patients for whom surgical resection is contraindicated because of poor liver function or the presence of multiple tumors in the liver [10]. MCT is less invasive than hepatectomy with respect to preserving postoperative liver function [11], and is considered as effective as surgery for treating HCC [5] and multiple metastatic liver cancer [12].

On the other hand, intrahepatic recurrences after MCT have been encountered as frequently as after hepatic resection [5], [12]. Recurrence after hepatectomy has been explained in part by local cytokine activation that may contribute to enhanced tumor growth in the remnant liver [13]. Although MCT is less invasive than hepatectomy, little is known about cytokine changes in the circulation and liver after MCT, and it is unclear whether MCT accelerates the growth of untreated tumors in the liver. This prompted us to examine the growth of untreated tumors and levels of growth factors in both plasma and the liver in rats that underwent MCT and in those that did not.

Section snippets

Animal model and tumor cell line

Adult male Donryu rats (200–230 g) were maintained under controlled temperature and humidity with a 12 h light/dark cycle and were provided water and standard laboratory diet ad libitum. The study was approved by the Animal Studies Committee of Oita Medical University. During the surgical procedures, rats were anesthetized with an intraperitoneal injection of 40 mg/kg sodium pentobarbital.

A rat ascites hepatoma cell line (AH-130) was used for the intrahepatic tumor model, as described

Results

To examine differences in tumor growth between the MCT and control groups, tumors were weighed preoperatively and on POD 1, 3 and 5. The mean preoperative tumor weight (i.e. 5 days after tumor implantation) was 11.8 mg. Tumor weights in both the MCT and control groups at POD 1 were similar to the preoperative value (Fig. 1). On POD 3, the mean tumor weights in the MCT and control groups were 53.8±22.7 and 31.0±12.0 mg, respectively (P=0.056). Two days later, on POD 5, the mean tumor weight in

Discussion

Surgical resections of both primary and metastatic hepatic malignancies have contributed to an improved patient prognosis. However, the postoperative intrahepatic recurrence rate remains considerably high. This may be due to portal venous spread and multicentric occurrence in HCC patients [16], [17]. Moreover, failure in detection of micrometastases prior to the surgery may result in early recurrence in the liver [18]. Following MCT in HCC patients, similar to hepatic resection, the 3 year

Acknowledgements

The authors thank Taiho Pharmaceutical Co., Ltd. for providing AH-130 cells. We also are grateful to Mr Shinji Yano and Ms Michiyo Hisaka for their technical assistance.

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