Pre-operative transarterial chemoembolization for resectable hepatocellular carcinoma adversely affects post-operative patient outcome

Background  Long‐term outcomes after hepatic resection for hepatocellular carcinoma are not satisfactory because of high recurrence rates. Aim  To assess whether a single session of pre‐operative transarterial chemoembolization affects post‐operative outcome. Methods  We analysed outcomes retrospectively in 334 consecutive patients who underwent hepatic resection for hepatocellular carcinoma, initially judged resectable. Ninety‐seven of these patients had each undergone a single session of pre‐operative transarterial chemoembolization (transarterial chemoembolization + hepatic resection group), whereas 237 had not (hepatic resection group). Results  Most clinicopathological characteristics were similar in the two groups. The overall survival rate was significantly higher in the hepatic resection than in the transarterial chemoembolization + hepatic resection group (P = 0.011), whereas their disease‐free survival rates were comparable (P = 0.67). The overall and disease‐free survival rates of the transarterial chemoembolization + hepatic resection group with incomplete tumour necrosis were significantly lower than those of the hepatic resection group (P < 0.001 and P = 0.006, respectively). Multivariate analysis showed that pre‐operative transarterial chemoembolization, serum alpha‐fetoprotein elevation (>1000 ng/mL), tumour size (>5 cm) and vascular invasion were independent risk factors for poor overall survival after hepatic resection. Conclusions A single session of pre‐operative transarterial chemoembolization for initially resectable hepatocellular carcinoma worsens overall survival rate. It may also increase the risk of tumour recurrence in patients who achieve incomplete tumour necrosis.     

Survival of patients with early hepatocellular carcinoma treated by percutaneous alcohol injection

BACKGROUND: Once small (<10 mm) nodules, suspicious for hepatocellular carcinoma, are detected in cirrhotics, the European Association for the Study of the Liver guidelines recommend to delay histological confirmation and treatment until they increase in size. AIM: To validate this policy by evaluating survival of 450 cirrhotics in Child-Pugh class A or B with unifocal 'early' hepatocellular carcinoma treated by percutaneous alcohol injection. METHODS: Patients were sorted by nodular size into three groups: < or =10 mm (n = 36, group A), >10 to < or = 20 mm (n = 142, group B) and >20 to < or = 30 mm (n = 272, group C). Overall and tumour-free survivals were estimated by Kaplan-Meier method. RESULTS: In groups A, B and C, mean follow-up was 33 +/- 26, 34 +/- 22 and 35 +/- 25 months (P = 0.89), mean survival time was 63 +/- 54, 57 +/- 48 and 62 +/- 66 months (P = 0.69) and mean tumour-free survival was 44 +/- 47, 46 +/- 58 and 41 +/- 68 months (P = 0.51), respectively. When patients were sorted by Child status, mean survival time was 76 +/- 82 and 38 +/- 29 months in Child A and B (P < 0.0001). CONCLUSIONS: The comparable survival of percutaneous alcohol injection-treated patients with single, early hepatocellular carcinoma sorted by nodular size supports the European Association for the Study of the Liver 'wait-and-see' policy for patients with lesions <10 mm, and suggests that allowing the nodules to grow prior to taking further diagnostic or therapeutic actions would not harm these patients.     

CIK细胞治疗中晚期肝细胞肝癌的临床研究

目的评估细胞因子诱导的杀伤细胞(C IK细胞)过继免疫疗法治疗中晚期肝细胞肝癌的临床疗效。方法144例中晚期肝细胞肝癌患者,随机分为4组:单纯肝动脉插管栓塞化疗即单介入(TACE)组30例,肝动脉插管栓塞化疗联合经皮肝瘤体内注入无水乙醇即双介入(TACE PE I)组62例,C IK细胞回输联合单介入组16例,C IK细胞回输联合双介入组36例,进行治疗前后的疗效比较。结果C IK 双介入组、双介入组、C IK 单介入组、单介入组近期有效率分别为91.7%、75.8%、75.0%、43.3%;C IK联合介入组的AFP下降、细胞免疫功能、卡氏评分均优于双介入组和单介入组,生存期也显著延长。结论C IK细胞联合介入治疗中晚期肝细胞肝癌增强了抗癌效果,改善了患者的生存质量,延长了患者的生存期。     

Clinical trial: percutaneous acetic acid injection vs. percutaneous ethanol injection for small hepatocellular carcinoma – a long-term follow-up study

Background  The long-term outcome of percutaneous acetic acid injection (PAI) and percutaneous ethanol injection (PEI) for treating small hepatocellular carcinoma (HCC) remains unclear.
Aim  To compare the long-term outcome of PAI vs. PEI for treating small HCC.
Methods  From July 1998 to July 2004, 125 patients with small HCC were enrolled. Seventy patients receiving PAI and 55 patients receiving PEI were enrolled. There were no significant differences in the clinical characteristics between the two groups. Tumour recurrence and survival rates were assessed.
Results  Mean follow-up time was 43 months. The local recurrence rate and new tumour recurrence rate were similar between the PAI and PEI groups. The PAI group had significantly better survival than the PEI group ( P  = 0.027). Multivariate analysis revealed that PAI was the significant factor associated with overall survival [PAI vs. PEI, RR: 0.639, 95% CI: (0.419–1.975), P  = 0.038]. The treatment sessions required to achieve complete tumour necrosis were significantly fewer in the PAI group than in the PEI group (2.4 ± 1.0 vs. 2.9 ± 1.3, P  = 0.018).
Conclusion  Percutaneous acetic acid injection required fewer treatment sessions than PEI and provided better survival after long-term follow-up.     

Review article: percutaneous treatment of hepatocellular carcinoma

In early stage hepatocellular carcinoma (HCC), liver transplantation, surgical resection and percutaneous techniques are classified as radical treatments, and may be offered to about 25% of all patients with HCC evaluated in referral centres. The restricted inclusion criteria for surgical resection and the shortage of liver donors for transplantation have stimulated an increasing demand for minimally invasive treatments able to achieve effective and reproducible percutaneous tumour ablation, with less associated morbidity and lower cost than other interventions. Among percutaneous techniques, ethanol injection has proven to be highly effective in single HCC up to 3 cm, with a rate of complete response of 80%, being well tolerated and with a limited risk of minor complication. In larger and/or multinodular HCC the efficacy is reduced to 50% of complete response in nodules between 3 and 5 cm, and to lower rate in larger tumours. Alternative options to ethanol injection have been recently proposed, including radiofrequency, microwave and laser thermal ablation, aimed to extend the necrotic area thus improving the rate of complete response. To date, radiofrequency is the most used technique, with a reported rate of complete response of 90-98% in nodules smaller than 3 cm, and with the advantage of fewer sessions, otherwise counteracted by a higher rate of side-effects. Microwave and laser are promising technologies, but only few clinical data are available. Randomized controlled trials are needed in order to assess treatment response, long-term survival, rate of complication and cost-efficacy of newer technologies in comparison to ethanol injection.     

肝动脉化疗栓塞结合B超治疗原发性肝癌

目的观察肝动脉化疗栓塞（TACE）结合B超引导下经皮肝穿瘤内注射30％的醋酸（PAI）治疗原发性巨块型肝癌的临床疗效。方法对23例中、晚期巨块型肝癌均先采用肝动脉化疗栓塞术,术后15—20d再在B超下经皮肝穿瘤内注射30％的醋酸2～3次。结果治疗2个周期后比较患者治疗前后AFP降低程度和肿块缩小情况有显著性的差异（P〈0．01）,1、2年生存率分别为91％和82％。结论醋酸有望取代无水乙醇与TACE结合用于肝癌的介入治疗。     

介入治疗肝癌合并梗阻性黄疸患者的疗效及术后护理

目的总结肝癌合并梗阻性黄疸介入治疗的护理方法。方法商丘市第一人民医院2007年10月至2010年10月收治的肝癌合并梗阻性患者30例,全部行经皮肝穿刺胆汁引流或胆管内支架植入术治疗。介入治疗后密切观察黄疸症状,做好饮食护理、疼痛护理、引流管护理,监测肝功能指变化。结果本组2例患者治疗前后血胆红素无明显变化,术后因肝性脑病死亡。其余患者治疗前后,黄疸明显减退,胆红素和丙氨酸转氨酶明显降低,前后比较差异统计学意义(P<0.05);存活患者中,2例患者出现血性引流液,5例患者出现血淀粉酶升高,3例患者出现引流管周围渗漏腹水,经积极治疗及护理后好转。结论介入治疗肝癌合并梗阻性黄疸可以较好的降低患者血胆红素,但术后血胆红素未明显变化者应警惕肝性脑病的出现;及时做好的并发症的治疗及护理,可提高患者生存质量,延长生存时间。     

Different presentation of hepatitis B-related hepatocellular carcinoma in a cohort of 1863 young and old patients - implications for screening

AIM: To compare the clinico-pathological features of hepatitis B virus-related hepatocellular carcinoma in young and old patients. METHODS: The clinico-pathological characteristics of hepatitis B virus-related hepatocellular carcinoma were compared in 1863 consecutive patients (121 patients, 40 years) seen at a single institution over the last 13 years. RESULTS: Young patients presented more often with pain (P < 0.0001), hepatomegaly (P = 0.01) and ruptured hepatocellular carcinoma (P = 0.02), whereas old patients presented with ankle oedema (P = 0.001), ascites (P = 0.002) and by routine screening (P = 0.035). Liver function, Child-Pugh grading and indocyanine green test were better preserved in young patients. They also had a higher alpha-foetoprotein concentration (P = 0.001), larger tumour size (P = 0.001) and more frequent metastasis (P = 0.008), but a similar surgical resection rate (33.6% vs. 28%), to old patients. There was no difference between the two groups in the overall post-resection survival rate, but there was a shorter survival in young patients with unresectable disease (3.6 months vs. 4.6 months, P = 0.004). Young patients with hepatocellular carcinoma often show a later presentation, but a higher resectability rate and similar survival rates, than old patients. The screening programme should include young hepatitis B virus carriers, even in the absence of cirrhosis.     

超声引导下经皮经肝无水乙醇注射联合索拉非尼口服治疗原发性肝癌临床评价

目的 探讨超声引导下经皮经肝无水乙醇注射联合索拉非尼治疗原发性肝癌的临床效果及对术后复发情况的影响。方法 选取沧州市传染病医院2014年1月至2015年12月收治的原发性肝癌患者92例,按随机数字表法分为观察组和对照组,各46例。两组患者均予超声引导下经皮经肝无水乙醇注射治疗,观察组患者加服甲苯磺酸索拉非尼片。统计并比较两组患者的近期疗效、血清肿瘤标志物水平、不良反应发生率,并门诊随访3年以观察肿瘤复发率、远端转移率、死亡率。结果 观察组近期有效率为86.96%,明显高于对照组的69.57%(P<0.05);治疗后,观察组患者的甲胎蛋白(AFP)、癌胚抗原(CEA)、血管内皮生长因子(VEGF)水平均明显低于对照组(P<0.05);治疗期间,观察组不良反应发生率为21.74%,与对照组的13.04%相当(P>0.05)。门诊随访3年,观察组肿瘤复发率、远端转移率、死亡率均明显低于对照组(P<0.05)。结论 超声引导下经皮经肝无水乙醇注射联合索拉非尼口服治疗原发性肝癌,能提高近期疗效,降低患者体内血清肿瘤标志物水平和复发率。     

肝细胞癌化疗栓塞后经皮瘤内注射无水乙醇的疗效

目的比较肝动脉化疗栓塞术(THAE)后经皮瘤内注射无水乙醇(PEI)与单纯THAE治疗单个肝细胞癌的疗效。方法53例肝细胞癌随机分成A(26例)、B(27例)两组。A组单纯THAE治疗;B组THAE治疗后,在CT引导下行PEI治疗。结果THAE组肿瘤治疗的部分缓解率为26.7%,1、2、3年生存率分别为56.0%、30.0%、0.0%。THAE+PEI组肿瘤治疗的部分缓解率为55.5%(P<0.05),1、2、3年生存率分别为91.0%、57.0%、22.0%(P<0.05)。结论THAE+PEI较单纯THAE对单个肝细胞癌的治疗更安全有效。     

Systematic review: evidence-based management of hepatocellular carcinoma--an updated analysis of randomized controlled trials

The treatment strategy of hepatocellular carcinoma applied following scientific guidelines is only supported by 77 randomized controlled trials published so far, a figure that clearly pinpoints hepatocellular carcinoma as an 'orphan' cancer in terms of clinical research when compared with other high-prevalent cancers worldwide. A systematic review analysing 61 randomized controlled trials (1978-2002) showed a modest survival benefit from chemoembolization in patients with intermediate tumours, and the lack of an effective first-line treatment option for patients with advanced disease. These conclusions have been endorsed by the European Association for the Study of the Liver and the American Association for the Study of Liver Diseases. The present updated evidence-based approach includes 16 randomized controlled trials published from 2002 to 2005 assessing percutaneous ablation (seven), other loco-regional therapies (three) and systemic therapies (six). Eight showed high-quality methodological profiles. Four randomized controlled trials demonstrated a better local hepatocellular carcinoma control in tumours larger than 2 cm treated by radiofrequency ablation compared with ethanol injection. No survival advantages were obtained from systemic treatments in patients with advanced hepatocellular carcinoma, an area that is an unmet need. Therefore, there is an urgent request to conduct well-designed phase III investigations in hepatocellular carcinoma patients.     

原发性肝癌术后抗复发治疗

目的 探讨原发性肝癌根治性切除术后联合肝动脉插管栓塞化疗(TACE)、抗乙型肝炎病毒及免疫治疗抗复发治疗对术后复发的影响.方法 随访满2年的原发性肝癌根治性切除术患者60例,分为单纯手术组、术后综合治疗组各30例,对两组术后1年、2年肝内复发率进行回顾性分析.结果 综合治疗组1年、2年肝内复发率分别为13％(4/30)、40％(12/30),显著低于单纯手术组的40％(12/30)和70％(21/30)(x2=4.176、4.310,均P＜0.05).结论 原发性肝癌根治性切除术后联合TACE、抗乙型肝炎病毒及免疫治疗的肝癌综合治疗方案可以延缓肝癌手术后复发.     

TACE联合经皮经肝门静脉穿刺PEI治疗HCC合并PVTT的临床研究

目的探讨肝动脉化疗栓塞（11ACE）联合经皮经肝门静脉穿刺无水酒精注射（PEI）治疗原发性肝癌（HCC）合并门静脉癌栓（PVTT）的临床疗效及安全性。方法2007年6月-2010年10月对30例不能手术治疗的HCC合并PVTT患者行TACE联合经皮经肝门静脉穿刺PEI治疗。结果1个疗程治疗后行CT检查示：PVTT消失或缩小5例,占16：7％,癌栓未增大17例,占56．7％;25例AFP值升高患者中19例AFP值下降,占76％;随访0．5、1、2年生存率分别为86．7％（26／30）、53．3％（16／30）、10．0％（3／30）,全部病例未出现出血、气胸、胆漏、肝功能衰竭、针道种植转移等严重并发症。结论TACE联合经皮经肝门静脉穿刺PEI治疗HCC合并PVTT是一种安全、有效的治疗方法,并发症少。     

手术治疗肝癌合并门静脉癌栓的效果

目的探讨原发性肝癌(HCC)合并门静脉癌栓(PVTT)的外科治疗效果。方法 63例肝癌合并门静脉癌栓患者中,17例(A组)行肝癌切除加门静脉癌栓取栓术,术后再加大网膜静脉双插管灌注化疗;其余46例(B组)行非手术治疗,包括射频治疗24例、无水酒精注射14例、介入治疗8例。结果 A组术后1、2和3年的生存率分别为65.2%、41.2%、23.5%,明显高于B组的45.7%、28.3%和0%(P<0.05)。结论与非手术治疗比较,手术治疗能相对延长肝癌合并门静脉癌栓患者的生存时间,方便术后使用大网膜静脉插管灌注化疗。     

Long-term survival of patients with unresectable hepatocellular carcinoma treated with transcatheter arterial chemoinfusion

BACKGROUND: Transcatheter arterial chemoembolization (TACE) has become one of the most common treatments for unresectable hepatocellular carcinoma. Published studies of TACE report a 5-16% risk of serious complications. Compared with TACE, transcatheter arterial chemoinfusion (TACI) may have similar efficacy and fewer side effects. AIM: To examine the clinical outcomes of TACI. METHODS: We performed a retrospective cohort study of 345 consecutive TACI cases in 165 patients performed at a single United States medical center between 1998 and 2002. Primary outcomes were tumour response and survival rates. RESULTS: Only seven patients were hospitalized for more than 24 h after the procedure, and only three patients had worsening of liver function within 30 days of TACI. Survival was significantly poorer for patients with tumour-node-metastasis (TNM) IV compared to those with TNM I-III and also for patients with Child's class B/C vs. A. Following adjustment for age, gender, ethnicity and aetiology of liver diseases, independent predictors of poor survival were Child's class B/C [Hazard Ratio (HR) = 1.69, P = 0.024] and TNM IV staging (HR = 1.63, P = 0.014). CONCLUSIONS: TACI appears to be safe and effective for unresectable hepatocellular carcinoma with TNM stage I-III; randomized controlled trials are needed to compare TACI to TACE.     

Intra‐arterial therapy with cisplatin suspension in lipiodol and 5‐fluorouracil for hepatocellular carcinoma with portal vein tumour thrombosis

Aliment Pharmacol Ther 2010; 32: 543–550

Summary

Background Portal vein tumour thrombosis is a negative prognostic factor for hepatocellular carcinoma (HCC). Aim To assess the efficacy of cisplatin in lipiodol emulsion combined with 5‐fluorouracil (5‐FU) for patients with HCC and portal vein tumour thrombosis. Methods The study subjects were 51 patients with the above‐specified criteria who received injection of cisplatin suspension in lipiodol emulsion followed by intra‐arterial infusion of 5‐FU. The primary objective was to determine tumour response to the treatment, while the secondary objectives were safety and tolerability. Independent factors for survival were also assessed. Results Ten patients had complete response and 34 patients had partial response (response rate, 86.3%). The median survival for all 51 patients was 33 months, while that for 10 complete response patients and 21 patients who showed disappearance of HCC following additional therapies was 39 months. The single factor that significantly influenced survival was therapeutic effect. Treatment was well tolerated and severe toxicity was infrequent, with only grade 3 toxicity (thrombocytopenia) in one patient. Conclusions The present study demonstrated the efficacy of hepatic arterial infusion chemotherapy using cisplatin‐lipiodol emulsion and 5‐FU without serious adverse effects in patients with unresectable HCC and portal vein tumour thrombosis.     

经皮肝穿刺射频热凝对原发性小肝癌患者疗效的监测研究

目的：比较经皮肝穿刺射频热凝术（PRFA）与手术切除治疗原发性小肝癌的临床疗效。方法按照实际治疗方式将例患者分为实验组46例和对照组50例,实验组患者给予PRFA治疗,对照组患者给予手术切除治疗,比较两组患者不良反应发生情况、肿瘤完全毁损（切除）情况以及3年复发和生存情况。结果两组患者并发症发生率比较,差异无统计学意义（P＞0.05）;两组患者肿瘤完全毁损率（完全切除率）比较,差异无统计学意义（P＞0.05）;两组患者3年复发率及生存率比较,差异无统计学意义（P＞0.05）。结论PRFA与手术切除治疗原发性小肝癌疗效相当,但PRFA是微创手术、创伤小、并发症轻、术后恢复快,临床应用价值更高。     

Hepatocellular carcinoma associated with chronic viral hepatitis. Aetiology, diagnosis and treatment

Two major aetiological factors have been definitively incriminated in the pathogenesis of HCC: these are chronic hepatitis and hepatic cirrhosis. Chronic infection with hepatotropic viruses may account for the majority of cases of hepatocellular carcinoma in high incidence areas, and a varying prevalence of human hepatitis B and hepatitis C virus infection appears to determine the differing geographical prevalence of hepatocellular carcinoma in high and low incidence areas of the world. Patients with advanced hepatocellular carcinoma have a grave prognosis. However, at-risk groups have been characterized, and recent advances in hepatic imaging and tumour marker testing have made screening for asymptomatic primary liver cancer feasible. It it not clear, however, whether screening for small hepatocellular carcinoma improves the prognosis. Lipiodol has been shown to serve as a useful vehicle for diagnosis of small, centimetre sized nodules of tumour, and for delivery of cancer chemotherapeutic or radioactive agents to HCC. The combination of early diagnosis, and coupled medical and surgical treatments including targeted lipiodol or monoclonal antibody conjugates and hepatic resection or transplantation may lead to an improved outlook for viral-associated hepatocellular carcinoma.     

Surgical treatment of hepatocellular carcinoma with cirrhotic esophageal varices and hypersplenism:a 184 case report

In treating hepatocellular carcinoma (HCC) patients with advanced cirrhosis, one of the most difficult problems is concomitant esophageal varices and hypersplenism. Whether these conditions should be treated surgically in association with HCC resection is still in debate. To elucidate whether esophageal devascularization or splenectomy is beneficial when simultaneously performed with liver resection in HCC patients with both varices and hypersplenism, HCC patients (n = 184) with esophageal varices and hypersplenism received one of the three treatments: simultaneous liver resection and esophageal devascularization (Group I, n = 41); simultaneous liver resection and splenectomy (Group II, n = 61); liver resection only (Group III, n = 82). The incidences of postoperative complications of the three groups were 31.7%, 29.5% and 24.4%, respectively, with no significant difference among them. The 5-year tumor-free survival rates for the group I, group II and group III were 34.1%, 36.1% and 37.8%, respectively. Variceal bleeding caused death by only 4.2% in group I, but by 14.3% in group II and 23.2% in group III. The survival rates in the group I and the group II were comparable to those in the group III, however, the recurrences of postoperative fatal variceal bleeding in group I and group II were significantly lower than those in group III. The results suggest that HCC patients with esophageal varices and hypersplenism should undergo hepatic resection plus esophageal devascularization or splenectomy if radical resection of HCC can be expected.     

原发性肝癌介入治疗中化疗栓塞模式的探索

为探讨空气作为栓塞剂在原发性肝癌介入中的应用并作出评价，选择１３例不能切除的原发性肝癌经肝动脉静灌注化疗后用空气２０～３０ｍｌ栓塞，２～３周一次，反复治疗２～４次，疗程末用碘油阿霉素乳剂作最后栓塞，治疗中观察血象，肝功能，ＡＦＰ和肿瘤大小的变化，并作长期随访。结果：治疗后肿瘤缩小５０％以上者３例，不足５０％者９例，变化不明显１例，随访结果６例生存不足６月，３例生存１０月，２例１２月，另２例生存超过