化学栓塞-经皮冷消融序贯治疗不能切除的原发性肝癌

Sequential treatment of unresectable primary liver cancer by transarterial chemoembolization-percutaneous cryoablation

目的评价经皮肝冷消融联合经肝动脉化学栓塞对不能切除的原发性肝癌(PLC)的治疗价值。方法360例PLC患者接受治疗。肝内瘤块均大于5 cm。其中220例肿瘤为单个,其余为多个,但不超过5个。伴门静脉癌栓、肝衰竭(血清胆红素>34 mol/L,凝血酶原时间超过正常对照3 s)和明显腹水者除外。所有病例经过仔细评价,均失去手术切除机会。化学栓塞系采用经皮经肝动脉插管,视肿瘤部位,插管至左或右肝固有动脉或支配肝肿瘤的动脉分支。一般为碘化油和明胶海绵双重栓塞,同时给予化疗药, 常用表阿霉素40-60 mg、顺铂100 mg、丝裂霉素10-20 mg等。2周后作CT观察栓塞效果,如果肿瘤已被碘化油完全充填,则予冷消融治疗,否则再作化学栓塞,但不超过3次。冷消融采用氩氦冷冻系统(Cryocare,USA)进行,氩气作为冷却剂,靶组织内温度达-160℃,维持15-20 min后,给予氦气复温至20℃,共给予2次冷却-复温循环。必要时冷消融治疗后1个月再作化学栓塞1-2次。结果在中位随访期21个月(6-36个月)内,B超和/或CT随访显示,肿瘤完全反应(CR)30例(8.3%),部分反应(PR)228例(63.3%),无明显改变(NC)66例(18.3%),进展(PD)36例(10.0%)。血清甲胎蛋白(AFP)229例治疗前为320±285 g/L,治疗后有199例(86.9%)下降至126±85 g/L(P<0.05),其中142例(62.0%)降至正常范围。呈CR和PR的258例中,有69例(26.7%)在治疗后4-15个月内复发,但其中仅11例(15.9%)在原冷冻部位复发,其余均为异位生长。半年生存率为90.6%,1年为70.0%,2年为52.1%,3年为41.1%。死亡113例,死因为肝癌广泛转移45例,食管静脉曲张大出血24例,自发性腹膜炎23例,肝性脑病14例, 其他非肝癌相关性疾病7例。结论经皮肝动脉化学栓塞-经皮冷消融序贯治疗对不能手术切除的PLC 有良好效果,能使肿瘤退缩,延长患者生命。

Objective To evaluate the effectiveness of sequential treatment of unresectable primary liver cancer (PLC) by transarterial chemoembolization (TACE) -percutaneous cryoablation. Method Three hundred and sixty patients with PLC received the therapy. Intrahepatic tumor masses were larger than 5 cm in size. Two hundred and twenty patients had single mass in liver and others had multiple masses but less than 5. The patients with portal vein thrombosis, hepatic failure (serum bilirubin > 34 mol/L, prothrombin time 3s longer than the control) and obvious ascites were excluded from the treatment schedule. The tumors of all patients were considered to be unresectable through comprehensive evaluation. Transarterial chemoembolization was performed routinely. The branches of the hepatic artery supplying the tumor were occluded at the arteriography by injection of lipiodol mixed with chemotherapeutic agents(adrimycin, cisplatin and mitomycin) and gelfoam. Two weeks later, if CT scanning showed good response, percutaneous cryoablation should be given, otherwise, the chemoembolization should be performed again (generally no more than 3 times). The cryoablation was performed with the Cryocare system (Endocare, USA) by using argon gas as a cryogen. Temperature in target tissue reached -160℃ for 10 to 15 min, and then, helium was sent to increase the temperature to 20℃. Two freeze-thaw cycles were performed. One month after cryoablation, the chemoembolization of one or two times may be further performed if necessary. Results During 21 months (6-36 months) follow-up period, ultrasound and /or CT showed that a complete response (CR) was obtained in 30 cases (8.3%), partial response (PR) in 228 cases (63.3%), no change (NC) in 66 cases (18.3%), and progressive disease (PD) in 36 cases (10.0%). Alpha-fetoprotein (AFP) was significantly decreased in 86.9% of patients, and 62.0% of patients was nonnal. Out of 258 patients with CR and PR, 26.7 % of patients had intrahepatic recurrence, but only 15.9% developed recurrence at cryosite. There were 113 patients who died during the follow-up period, and the death causes included widespread metastasis in 45 cases, esophageal variceal bleeding in 24 cases, spontaneous peritonitis in 23 cases, hepatic encephalopathy in 14 cases and other non-liver cancer-related causes in 7 cases. Conclusion Sequential treatment of TACE-percutaneous cryoablation offers a safe and effective treatment options, and may result in a shrinkage or eradication of tumor mass and increased survival for patients with unresectable PLC.