Long-term outcome of percutaneous ethanol injection therapy for minimum-sized hepatocellular carcinoma

AIM： To evaluate long-term follow-up of minimum-sized hepatocellular carcinoma （HCC） treated with percutaneous ethanol injection （PEI）. METHODS： PEI was applied to 42 lesions in 31 patients （23 male and eight female） with HCC 〈 15 mm in diameter, over the past 15 years. RESULTS： Overall survival rate was 74.1% at 3 years, 49.9% at 5 years, 27.2% at 7 years and 14.5% at 10 years. These results are superior to, or at least the same as those for hepatic resection and radiofrequency ablation. Survival was affected only by liver function, but not by sex, age, etiology of Hepatitis B virus or Hepatitis C virus, α-fetoprotein levels, arterial and portal blood flow, histological characteristics, and tumor multiplicity or size. Patients in Chiid-Pugh class A and B had 5-, 7- and 10-years survival rates of 76.0%, 42.2% and 15.8%, and 17.1%, 8.6% and 0%, respectively （P = 0.025）. CONCLUSION： Treatment with PEI is best indicated for patients with HCC 〈 15 mm in Child-Pugh class A.

Percutaneous ethanol injection, radiofrequency and their combination in treatment of hepatocellular carcinoma

AIM： To evaluate the therapeutic effect and the indication of percutaneous ethanol injection （PEI）, radiofrequency ablation （RFA） and their combination in treatment of hepatocellular carcinoma （HCC）. METHODS： Two hundred and fifty-five patients with HCC received treatment of PEI, RFA or their combination. Group1 （〈 3 on in diameter, n=85） was treated with PEI, group2 （〈 3 cm in diameter, n=153） with RFA. Group3 （〉3 cm in diameter, n=86） was divided into two groups. Group 3a （/7=34） was treated with RFA, while group 3b （n=52） was treated with RFA for 2 wk after transcatheter arterial chemoembolization or PEI. Contrast-enhanced sonography was performed for 61 patients before and after RFA. Liver function and serum alpha-fetoprotein （AFP） were measured for all patients. Changes of the lesions on ultrasound and contrast-enhanced CT/HRI were evaluated for assessing the therapeutic responses. The 1-, 2-, 3- and 5-year survival rates were recorded after treatment. RESULTS： In group 1, the complete necrosis rate of lesions after 1 mo was 77.6% （66/85）. The level of AFP declined conspicuously after 1 mo. The 1-, 2-, 3- and 5-year survival rate after treatment was 80.0% （52/65）, 60.4% （32/53）, 52.5% （21/40） and 33.3% （7/21）, respectively. In group 2, the complete necrosis rate of lesions after 1 moh was 92.2% （141/153）. The level of AFP decreased conspicuously after i mo. The 1-, 2-, 3- and 5-year survival rate after treatment was 94.6% （88/93）, 73.2% （52/71）, 63.5% （33/52） and 46.4% （13/28）, respectively. In group 3a, the complete necrosis rate of lesions after 1 mo was 23.5% （8/34）. AFPdropped down to the normal level in only one patient after 1 mo. The 1-, 2- and 3-year survival rate after treatment was 47.6% （10/21）, 42.9% （6/14） and 27.3% （3/11）, respectively. Only one patient was still alive after 5 years. In group 3b, the complete necrosis rate of lesions after 1 mo was 57.7% （30/52）. The level of AFP decreased after 1 mo. The 1-, 2-, 3- and S-year survival rate after treatment was 68.6% （24/35）, 46.2% （12/26）, 36.8% （7/19） and 27.3% （3/11）, respectively. CONCLUSION： The therapeutic effect of RFA on small HCC is better than that of PEI. Small HCC is the optimal indication of RFA. For recurrent HCC （diameter〉3 cm）, the combined treatment of RFA and PEI/ACE should be used.

Ethanol injection is highly effective for hepatocellular carcinoma smaller than 2cm

AIM： To analyze the long-term prognosis in a cohort of western cirrhotic patients with single hepatocellular carcinoma treated with ethanol injection.METHODS： One-hundred forty-eight patients with solitan/hepatocellular carcinoma were enrolled. The tumor diameter was lower than 2 cm in 47 patients but larger in the remaining 101 patients. The impact of some pre- treatment clinical and laboratory parameters and of tu- mor recurrence on patients＇ survival was assessed.RESULTS： Among the pre-treatment parameters, only a tumor diameter of less than 2 cm was an independent prognostic factor of survival. The occurrence of new nodules in other liver segments and the neoplastic portal invasion were linked to a poorer prognosis at univariate analysis. Patients with a single hepatocellular carcinoma smaller than 2 cm showed a better 5-year cumulative survival （73.0% vs 47.9%） （P = 0.009）, 3-year local re- currence rate （29.1% vs 51.5%） （P = 0.011）, and 5-year distant intrahepatic recurrence rate （52.g% vs 62.8%） （P = 0.054） compared to patients with a larger tumor. CONCLUSION： The 5-year survival rate of patients with single hepatocellular carcinoma 〈 2 cm undergoing ethanol injection is excellent and comparable to that achieved using radiofrequency ablation.

Local injection therapy for hepatocellular carcinoma

BACKGROUND: Hepatocellular carcinoma (HCC) is one of the most common malignant tumors in the world and ranks the third most common cause of cancer-related death. Surgical resection, liver transplantation and percutaneous ablation are generally considered the only curative treatment for early stage HCC. Besides the limitations of insufficient organ donors and a long waiting time for liver transplantation, however, resection is applied only to patients with good hepatic reserve and localized tumors, with a resectability of 30%. DATA SOURCES: Local ablation therapy, which is minimally invasive but contributes to the significant improvement of survival in patients with unresectable tumor, hasbeen widely used in treating small HCC. Among the techniques of local therapy, percutaneous ethanol injection (PEI) with a complete response in 80% of HCCs less than 3 cm has been accepted as an alternative to surgery in patients with small HCC. Moreover, percutaneous hepatic quantified ethanol injection (PHQEI) or PEI according to the standard criteria has been confirmed to benefit patients with HCC, especially when quantified ethanol is given at a short interval (QESI, the interval was 2-3 days). RESULT: Several limitations related to local percutaneous methods may result in incomplete therapeutic effect in case of larger HCC nodules (>3 cm). CONCLUSION: The combined use of different methods according to the clinical status of patients or tumors may be essential to the effective treatment of HCC.

Influence of percutaneous local therapy for hepatocellular carcinoma on gastric function

AIM:To investigate the influence of percutaneous local therapy on gastric myoelectrical activity in patients with hepatocellular carcinomas.METHODS:Forty-four patients with hepatocellular carcinoma(HCC) [27 males and 17 females,ranging in age from 49 to 81 years old(69.7 ± 8.01 years)] who were admitted for percutaneous local therapy were enrolled in this study.We examined clinical abdominal symptoms using the Gastrointestinal Symptom Rating Scale(GSRS) before and 3 d after percutaneous local therapy.We also measured cutaneous fasting and postprandial electrogastrography(EGG) recordings before and 3 d after percutaneous local therapy.RESULTS:We found that the percentage of normogastria in the fasting period was lower in the Child B group than in the Child A group(66.8% ± 8.6% vs 84.0% ± 3.8%).After percutaneous local therapy for HCC,the percentages of normogastria in the fasting period were significantly decreased(81.6% ± 3.5% vs 75.2% ± 4.5%).None of the postprandial EGG parameters changed significantly after percutaneous local therapy for HCC.Percutaneous local therapy for HCC reduced the power ratio(PR).In particular,the PR of tachygastria was significantly decreased after therapy(P < 0.01).However,no significant differences were found in the postprandial EGG parameters.Likewise,no significant differences were found in the calculated GSRS scores obtained from the questionnaire before and after therapy.CONCLUSION:Gastric slow-wave dysrhythmias were induced by percutaneous local therapy in HCC patients,even though the GSRS scores obtained from the questionnaire did not change significantly.

Prognostic factors for hepatocellular carcinoma recurrence

The recurrence of hepatocellular carcinoma,the sixth most common neoplasm and the third leading cause of cancer-related mortality worldwide,represents an important clinical problem,since it may occur after both surgical and medical treatment.The recurrence rate involves 2 phases:an early phase and a late phase.The early phase usually occurs within 2 years after resection;it is mainly related to local invasion and intrahepatic metastases and,therefore,to the intrinsic biology of the tumor.On the other hand,the late phase occurs more than 2 years after surgery and is mainly related to de novo tumor formation as a consequence of the carcinogenic cirrhotic environment.Since recent studies have reported that early and late recurrences may have different risk factors,it is clinically important to recognize these factors in the individual patient as soon as possible.The aim of this review was,therefore,to identify predicting factors for the recurrence of hepatocellularcarcinoma,by means of invasive and non-invasive methods,according to the different therapeutic strategies available.In particular the role of emerging techniques(e.g.,transient elastography)and biological features of hepatocellular carcinoma in predicting recurrence have been discussed.In particular,invasive methods were differentiated from non-invasive ones for research purposes,taking into consideration the emerging role of the genetic signature of hepatocellular carcinoma in order to better allocate treatment strategies and surveillance follow-up in patients with this type of tumor.

Review of dynamic contrast-enhanced ultrasound guidance in ablation therapy for hepatocellular carcinoma

Local ablative techniques-percutaneous ethanol injection, microwave coagulation therapy and radiofrequency ablation (RFA)-have been developed to treat unresectable hepatocellular carcinoma (HCC). The success rate of percutaneous ablation therapy for HCC depends on correct targeting of the tumor via an imaging technique. However, probe insertion often is not completely accurate for small HCC nodules, which are poorly def ined on conventional B-mode ultrasound (US) alone. Thus, multiple sessions of ablation therapy are frequently required in diffi cult cases. By means of two breakthroughs in US technology, harmonic imaging and the development of second-generation contrast agents, dynamic contrast-enhanced harmonic US imaging with an intravenous contrast agent can depict tumor vascularity sensitively and accurately, and is able to evaluate small hypervascular HCCs even when B-mode US cannot adequately characterize the tumors. Therefore, dynamic contrast-enhanced US can facilitate RFA electrode placement in hypervascular HCC, which is poorly depicted by B-mode US. The use of dynamic contrast-enhanced US guidance in ablation therapy for liver cancer is an effi cient approach. Here, we present an overview of the current status of dynamic contrast-enhanced US-guided ablation therapy, and summarize the current indications and outcomes of reported clinical use in comparison with that of other modalities.

Clinical outcome of small hepatocellular carcinoma after different treatments:A meta-analysis

AIM: To compare clinical outcomes between surgical resection (RES) and nonsurgical-RES (nRES) ablation therapies for small hepatocellular carcinoma (HCC).

Local recurrence is an important prognostic factor of hepatocellular carcinoma

AIM： To clarify the importance of complete treatment by PELT. METHODS： A total of 140 previously untreated cases of HCC were enrolled in this study from 1988 to 2002. The inclusion criteria were： a solitary tumor less than 4 cm in diameter or multiple tumors, fewer than four in number and less than 3 cm in diameter, without extrahepatic metastasis or vessel invasion. As general principles for the treatment of HCC, the patients underwent transcatheter arterial chemoembolization （TACE） prior to PEIT. After the initial treatment of the patients, ultrasonography and computed tomography were performed, and measurement of serum levels of α- fetoprotein （AFP） was determined. When tumor recurrences were detected, PEIT and/or TACE were repeated whenever the hepatic functional reserve of the patient permitted. We then analyzed the variables that could influence prognosis, including tumor size and number, the serum levels of AFP, the parameters of hepatic function （albumin, bilirubin, ALT, hepaplastin test, platelet number, and indocyanine green retention at 15 rain [ICG-R15]）, combined therapy with TACE, distant recurrence, and local recurrence. RESULTS： Univariate analysis identified the ICG test, serum levels of AFP and albumin, tumor size and number, and local recurrence, but not distant recurrence, as significant prognostic variables. In multivariate analysis using those five parameters, the ICG test, tumor size, tumor number, and local recurrence were identified as significant prognostic factors. In both univariate and multivariate analyses, the relative risk for the ICG test was the highest, followed by local recurrence. CONCLUSION： We found that local recurrence is an independent prognostic factor of HCC, indicating that achieving complete treatment for HCC on first treatment is important for improving the prognosis of patients with HCC. 2005 The WJG Press and Elsevier Inc. All rights reserved.

Management of small hepatocellular carcinoma in cirrhosis:Focus on portal hypertension

The incidence of hepatocellular carcinoma(HCC) is rising worldwide being currently the fifth most common cancer and third cause of cancer-related mortality.Early detection of HCC through surveillance programs have enabled the identification of small nodules with higher frequency,and nowadays account for 10%-15% of patients diagnosed in the West and almost 30% in Japan.Patients with small HCC can be candidates for potential curative treatments:liver transplantation,surgical resection and percutaneous ablation,depending on the presence of portal hypertension and co-morbidities.This review will analyze recent advancements in the clinical management of these individuals,focusing on issues related to the role of portal hypertension,the debate between resection and ablative therapies and the future impact of molecular technologies.

Hepatocellular carcinoma: Where are we?

Hepatocellular carcinoma(HCC) is the second cause of death due to malignancy in the world, following lung cancer. The geographic distribution of this disease accompanies its principal risk factors: Chronic hepatitis B virus and hepatitis C virus infection, alcoholism, aflatoxin B1 intoxication, liver cirrhosis, and some genetic attributes. Recently, type Ⅱ diabetes has been shown to be a risk factor for HCC together with obesity and metabolic syndrome. Although the risk factors are quite well known and it is possible to diagnose HCC when the tumor is less than 1 cm diameter, it remains elusive at the beginning and treatment is often unsuccessful. Liver transplantation is thus far considered the best treatment for HCC as it cures HCC and the underlying liver disease. Using the Milan criteria, overall survival after liver transplantation for HCC is about 70% after 5 years. Many attempts have been made to go beyond the Milan Criteria and according to recent works reasonably good results have been achieved by using a histochemical marker such as cytokeratine 19 and the so-called "up to seven criteria" to divide patients into categories according to their risk of relapse. In addition to liver transplantation other therapies have been proposed such as resection, tumor ablation by different means, embolization and chemotherapy. An important step in the treatment of advanced HCC has been the introduction of sorafenib, the first oral, systemic drug that has provided significant improvement in survival. Treatment of HCC patients must be multidisciplinary and by using the different approaches discussed in this review it is possible to offer prolonged survival and quite good and sometimes even excellent quality of life to many patients.

The clinical efficacy of percutaneous ethanol-lipiodol injection(PEI)combined with high-intensity focused ultrasound(HIFU)for small hepatocellularcarcinoma in special or high-risk locations

Objective The objective of this study was to explore the short-term effects and postoperative complications of ultrasound-guided percutaneous ethanol-lipiodol injection(PEI)combined with high-intensity focused ultrasound(HIFU)for the treatment of small hepatocellular carcinoma in a special or high-risk location.Methods Forty patients with small liver cancer in a special or high-risk location were randomly divided into two groups:20 patients were treated with PEI combined with HIFU(P+H group),and 20 patients were treated with HIFU alone(H group).There were no significant differences in average age,liver function,tumor location,tumor number,or tumor size between the two groups(P>0.05).Results Significant differences were observed in ablation parameters between the two groups(P<0.05).Under the same power,ablation rates of the P+H group were significantly higher than those in the H group,and postoperative complications in the P+H group were significantly lower than those in the H group(P<0.05).Conclusion The combination of PEI and HIFU has better clinical value than HIFU alone for small-cell liver cancer in special or high-risk locations.

Ablative techniques in hepatocellular carcinoma treatment

Hepatocellular carcinoma has been known to arise commonly in the setting of chronic liver disease. Due to its association with cirrhosis, patients with hepatocellular carcinoma often present with markedly diminished hepatic functional reserve, making them poor surgical candidates. For such patients, image-guided percutaneous ablative modalities have provided a viable alternate curative therapy. Although treatment allocation is a decision based on a number of factors, patients eligible for percutaneous ablation generally include those with early stage disease, hepatocellular carcinoma with disease limited to the liver and no extra-hepatic metastases. While percutaneous ethanol injection is the seminal technique, newer developments have led to it being replaced by percutaneous radiofrequency ablation as the most commonly employed procedure, due to a better efficacy as well as safety profile. Other ablative modalities including microwave ablation, laser ablation and cryotherapy are not as widely available. Furthermore, data comparing their effectiveness with well-established procedures like radiofrequency ablation is limited.

肝动脉栓塞及经皮注射乙醇治疗肝癌的研究

目的 比较肝动脉灌注化疗及栓塞 (TACE)加经皮注射无水乙醇 (PEI)与单纯TACE治疗有包膜、单个、大病灶原发性肝癌的疗效。资料与方法 45例原发性肝癌患者随机分成A、B两组。A组 (n =2 3)在预先经导管TACE治疗后 ,在B超引导下行PEI治疗。B组 (n =2 2 )单纯TACE治疗。结果 TACE组肿瘤治疗的部分缓解率仅为 9% ,1、2、3年生存率分别为 5 9%、32 %和 0 % ;病灶完全坏死率为 0 % (0 /5 )。相比之下 ,TACE +PEI组肿瘤治疗的部分缓解率增加到 40 % (P <0 .0 5 ) ,1、2、3年生存率分别为 88%、5 6 %和 2 1% (P <0 .0 5 ) ;病灶完全坏死率为 6 7%(4 /6 )。结论 PEI+TACE对有包膜的单个大病灶肝癌的治疗是安全、有效的 ,对这一部分患者进行二期切除手术也是有好处的。

超声造影对乙醇消融量化治疗肝癌疗效评判与随访价值

目的探讨超声造影对乙醇消融量化治疗肝细胞癌疗效判断以及在随访中的临床应用价值。方法经超声引导无水乙醇消融量化治疗肝癌54例,计54个肿瘤结节,分为A、B、C三组。A组于乙醇消融治疗结束时以及治疗后1个月复查,B组于治疗后12～14个月复查,C组于治疗24个月后复查。采用彩色多普勒超声及超声造影技术观察肿瘤结节大小、内部回声、血流及造影改变,并行超声引导穿刺活检。结果二维超声检查3组肝癌结节均较治疗前有不同程度缩小。A组肿瘤结节治疗结束时均为高回声,1个月后表现高回声或偏高回声者为52.4%(11/21),明显低于B、C两组表现为高回声或偏高回声的87.5%(14/16)、88.2%(15/17)(均P<0.05),而B、C两组间无明显差异(P>0.05)。彩色多普勒超声检查各组均未见血流信号。超声造影检查,A组结节在治疗结束时造影剂缺损区直径均超出原肿瘤,除A组3个肿瘤结节内见小片区域轻微增强外,余51个结节均未见增强。细针活检除A组3个结节内见残留肝癌细胞外,余均为纤维瘢痕组织及坏死组织。结论超声造影可较好评判肝癌乙醇消融量化治疗疗效,随访中能提供更多的诊断信息。

射频消融对比经皮无水乙醇注射治疗早期肝癌的Meta分析

目的 探讨射频消融对比经皮无水乙醇注射治疗早期肝癌的效果和安全性.方法 检索Cochrane library（截止至2014年第7期）、PubMed、Web of Science、CNKI、VIP、万方数据库（截止至2014年7月）.采用Cochrane协作网推荐的Cochrane Handbook for Systematic Reviews of Interventions （5.1.0）进行质量评价.采用RevMan 5.2软件进行统计学分析.结果 共纳入7个随机对照试验,包括1 084例患者,其中射频消融组545例,无水乙醇注射组539例.Meta分析结果提示：与经皮无水乙醇注射治疗早期肝癌相比,射频消融在总生存率（RR：1.14,95％CI：1.06～1.22,P=0.0003）、总复发率（RR：0.84,95％CI：0.71～0.99,P=0.03）显示出更多的优势,且不增加主要并发症的发生率（RR：1.33,95％CI：0.73～2.42,P=0.35）.结论 在早期肝癌的治疗中,与经皮无水乙醇注射相比,射频消融显示出更多的优势.

原发性小肝癌射频消融与无水乙醇注射治疗对比研究

目的探讨射频消融(RFA)和经皮穿刺无水乙醇注射治疗(PEIT)治疗原发性小细胞肝癌(SHCC)患者的最佳适应证。方法对127例SHCC进行了RFA和PEIT,其中RFA组81例共97个病灶,PEIT组46例共59个病灶。比较患者RFA及PEIT 1、2、3、4、5年生存率和并发症,统计两组患者的医疗费用。结果两组患者术后均无严重并发症;RFA组术后1、2、3、4、5年生存率分别为91.3%、76.4%、62.8%、51.7%和44.4%;PEIT组病患者术后1、2、3、4、5年生存率分别为78.0%、60.0%、47.8%、37.5%和33.3%;RFA组患者平均治疗费用明显高于PEIT组。结论对于SHCC,RFA疗效优于PEIT;对于位于肝包膜下、大血管分支旁、血供丰富的SHCC,以PEIT为宜;PEIT费用低廉,患者依从性较好。

1,6-二磷酸果糖醛缩酶对无水酒精注射治疗原发性肝癌中的观察

目的:探讨血清1,6-二磷酸果糖醛缩酶(FDP-ALD)测定对经皮肝穿无水酒精瘤内注射术(PEI)治疗原发性肝癌的疗效评价。方法:18例共24个肝癌肿瘤结节行PEI治疗,检测治疗后不同时点的血清FDP-ALD和甲胎蛋白(AFP)的变化并进行比较。结果:血清FDP-ALD活性在第1次PEI术后达最高值,随后呈波浪状下降,第8次回到术前水平,提示血清FDP-ALD活性变化可反映肝癌组织的坏死程度。血清AFP浓度治疗后也呈下降趋势,术前、术后比较差异有显著性(P<0.05)。结论:血清FDP-ALD活性测定可用于肝癌PEI的疗效评价,对AFP阴性的肝癌患者也有判断疗效的价值。

肝癌患者无水酒精治疗前后外周血IL-6、TGF-β_1的变化

目的监测超声引导下经皮无水酒精注射术(PEI)治疗前、后肝细胞癌患者外周血中细胞因子白介素6(IL-6)、转化生长因子β1(TGF-β1)的动态变化,分析PEI治疗对患者机体免疫功能的影响。方法采用酶联免疫吸附法检测30例原发性肝癌患者在PEI治疗前和治疗3次、6次、8次后IL-6、TGF-β1的改变,并与健康对照组比较。结果 PEI治疗前IL-6、TGF-β1高于对照组(P<0.01)。IL-6、TGF-β1PEI治疗3次后较治疗前升高(P<0.05);治疗6次后均降低到治疗前水平;治疗8次后IL-6继续下降,但与治疗前比较差异无统计学意义(P>0.05),而TGF-β1较治疗前降低明显(P<0.05)。结论 PEI能有效杀死肿瘤细胞,降低肿瘤负荷,增加机体的免疫功能。但PEI早期可能会导致机体出现短期的免疫抑制。

经肝动脉化疗栓塞与射频消融和无水乙醇注入对大肝癌的疗效评价及预后分析

目的探讨肝动脉化疗栓塞(TACE)联合射频消融(RFA)及无水乙醇注入术(PEI)治疗原发性大肝癌的临床效果及预后情况。方法选取2006年至2010年诊治的原发性大肝癌92例,其中15例行TACE联合RFA(Ⅰ组),29例行TACE联合PEI(Ⅱ组),21例行TACE、RFA联合PEI(Ⅲ组),仅行TACE 27例(Ⅳ组)。分析比较4组的临床疗效及总生存时间(OS),用COX比例风险模型分析预后因素。结果 4组相比,肿瘤缩小及肿瘤坏死率均有统计学意义(P=0.008,P=0.026);Ⅰ、Ⅱ、Ⅲ和Ⅳ组OS分别为18、14、20和10个月,差异有统计学意义(P=0.000);多因素结果分析显示,门脉癌栓及术前AFP值是影响总生存时间的预后因素(P=0.028,P=0.031)。结论 TACE、RFA联合PEI治疗大肝癌与TACE联合RFA/PEI或TACE相比,可明显提高肿瘤缩小、坏死率,延长生存期。