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

Cryoablation has proved to be an effective mean for ablation of small HCC as well as larger ones. Ethanol ablation has been long used as a method of treating small HCC. However, for large HCC ethanol ablation has met high failure rate because the areas of necrosis induced by ethanol are too small and ethanol diffuses poorly beyond the tumor that limits obtaining safety margin. On the other hand, cryoablation can achieve larger area of tumor necrosis (>10 cm in diameter) in fewer treatment sessions in comparison with ethanol ablation. The challenge of treatment of large HCC tumors (>10 cm) requires combination of techniques in order to achieve maximal therapeutic effectiveness and to minimize the side effects.

It is hypothesized that cryoablation followed by ethanol ablation would increase the volume of tumor necrosis due to their different but theoretically synergetic mechanisms (chemical and freezing effects). This study is retrospective analysis of effectiveness of such combination for the treatment of large HCC.

Technique

Eighty patients with large HCC tumors (>5cm in diameter) were enrolled in this study. All patients had large HCC tumors (>5cm in diameter) ranging between 5.5 and 14 cm with a mean diameter of 7.8 cm. The protocol consisted of a single cryoablation session including multiple overlapping cryoprobes followed (after 2–3 weeks) by repeated ethanol ablation sessions.

Cryoablation: Percutaneous cryoablation was performed under local anesthesia and guidance of ultrasound (US) and CT. The cryosurgical device was Cryocare Surgical System (Endocare, Inc., USA) adapted with multiple cryoprobes of different gauges. After skin disinfection, the cryoprobe was advanced toward to the tumor under US-guidance. The tip of the probe was kept 0.5cm beyond the tumor margin in its center direction. Selection of probe size was determined based on the tumor size. Generally, multiple cryoprobes were placed in a single lesion in an attempt to cover the largest possible volume of the tumor. Once the probe was positioned, freezing was initiated by infusing argon gas, creating a temperature below -160 C at the tip of probe. A freezing phase persisted for 15 minutes. Once the maximal size of the iceball was reached, thawing was then followed with infusing helium gas. Two freezing-thawing cycles were performed on each lesion, attempting to create a freeze zone covering entire lesion and at least 1cm beyond the margin of the tumor. Finally, the cryoprobe was removed when the tip temperature reached above 0°C.

Ethanol ablation: Ethanol ablation of the freezing tissue was given at 2-3 weeks after the cryoablation session. A 22 or 23 gauge needle was inserted percutaneously into the lesions under ultrasound guidance and sterile 100% ethanol was then injected into the area. The volume of the ethanol (V) injected was calculated according to the following formula: [V =4/3π(r+0.5)3], where V is the volume of ethanol to be injected and r is the radius of the tumor. Attempt was made to position the tip of the needle in the portion of the tumor where residual viable tissue was detected based on CT and ultrasound imaging analysis, In each session, 8-12 ml of ethanol were slowly injected over 3-5 min. The needle’s tip was repositioned in order to cover other portions of the tumor. Injection of ethanol was conducted twice weekly for 2-6 weeks according to the size of residual tumor.

Results

Results showed that the volume of tumor necrosis initially induced by cryoablation has been significantly increased after adjuvant ethanol ablation sessions. The complete necrosis was only seen in 56.3% of patients after cryoablation. Following ethanol ablation, ultimately, 88.8% of the patients have attained complete necrosis by the end of the protocol. The difference between the percentages of tumor necrosis before and after the ethanol ablation sessions showed statistical significance (p< 0.001). All the patients with HCC were followed for median 26 months with a range of 4-67 months. There were 30 patients (37.5 %) who showed no evidence of disease, 20 (25%) alive with recurrent HCC, 25 (31.3%) died of the cancer recurrence, and 5 (6.2%) died of causes other than HCC. There were only 4 patients (5.0%) who had local recurrence in the cryoablation sites. The 1, 2, 3, 4 and 5 years survival rates were 83%, 64%, 58%, 52%, and 43%, respectively. Five-year-disease-free survival rate was 27%.

Conclusion

Sequential use of percutaneous cryoablation and ethanol ablation could result in complete necrosis of large HCC in significantly more patients than percutaneous cryoablation alone, and effectively improve survival of the patients. This protocol of treatment should be used as the choice for unresectable large HCC.