Lizhi Niu, M.D., Kecheng Xu, M.D.*, Weibing He, M.D., Yisong He, M.D., Jiansheng Zuo, M.D.
Cryosurgery Center for Cancer, Fuda Cancer Hospital Guangzhou, Guangzhou 510300, China

*Corresponding Author: Kecheng Xu, M.D., Email: xukc@vip.163.com

Introduction

Cryosurgery has been used for two decades for the treatment of many benign, malignant, and metastatic tumors. More specifically, hepatocellular carcinoma (HCC) has been successfully treated either with cryosurgery alone or in combination with resection.

Transarterial chemoembolization (TACE), by itself, is not associated with improved survival, however, has been proved to shrink the mass of HCC. It is shown that sequential TACE-resection might improve outcome for the patients with large HCC. Therefore, combination of TACE and cryosurgery is expected to yield better therapeutic efficacy and to decrease the incidence of hemorrhage.

From March 2001 to December 2006, a total of 980 patients with HCC received operative or percutaneous cryosurgery in our hospital, among whom, 660 received TACE before cryosurgery. In this report, we reported the results of 420 patients who were treated with percutaneous cryosurgery either with or without.

Technique

Four hundred and twenty patients were enrolled in this study. All the patients were considered to have the tumors that are unresectable or whose surgical resection was not feasible because of the tumors’ locations or sizes or the patients’ morbidity. TACE was performed according to routine technique.

Percutaneous cryosurgery was performed under guidance of ultrasound or CT two to four weeks after TACE. Right lateral intercostals access was used for probe placement in most cases. Selection of cryoprobe depends upon the tumor size and number. Small lesions were ablated with one or two 2-mm probes. For larger lesions, larger caliber of probes (5mm or 8mm) was used. The probes were placed in the centre of the tumor under real-time ultrasound guidance. When multiple probes were used, the probes were placed 1.5-2 cm apart in the tumor periphery. Once the probe was positioned, freezing was initiated by argon/helium-based cryosurgery system (EndoCare, Inc., Irvine, Calif. USA).Two freeze cycles (20 minute each) were applied with 10–15 minutes of helium thaw following each cycle. An ice-ball was generated under continual sonographic monitoring until it encompassed the entire tumor mass and at least 1 cm beyond the margins of the tumor mass. Once the probe was removed, the tract was filled with Gelform strips soaked in thrombin.

Results

During a mean follow-up of 36±17 months (range 24 to 60 months),129 patients (30.7%) showed no evidence of disease, 98 patients (23.3%) were alive with recurrent disease,170 patients (40.5%) died of disease recurrence or spread, and 23 patients (5.5%) died of other diseases. The overall 1-,2-,3-,4-,and 5-year survival rates were 72%, 57.5%, 47%, 39% and 31%, respectively (Table I). The survival rates at 4 and 5 years post treatment were statistically significant different between TACE-cryosurgery combination and cryo-alone groups. Twelve-month-disease-free survival rate was 31% for the combination therapy and 25% for cryo-alone group (p=0.06), while 5-year-disease-specific survival was 26% and 12%, respectively (p=0.002).The local recurrence rate at the ablation area was 17% for all patients, and 11% and 23 % for combination therapy and cryo-alone group, respectively (p=0.04). The overall complication rate was 24%, and there were 21% and 26.2 % of complication rate, respectively, for combination and cryo-alone groups (p= 0.06).The latter group had more incidences of hepatic bleeding (p=0.02) and liver rupture, while the combination therapy group had more cases of liver failure.

Conclusion

A combined approach involving TACE and perctaneous cryosurgery improves survival. TACE is useful in controlling tumors burden. Sequential use of TACE and cryosurgery seems to be the best way to improve outcome in unresectable HCC.

Key words: Hepatocellular carcinoma, Cryosurgery, Transarterial chemoembolization.

Table I
Survival and disease status of TACE+cryoablation combination vs. cryo-alone groups.