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.

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.

Guide for diagnosis and treatment of hepatocellular carcinoma

Hepatocellular carcinoma(HCC) is ranked as the 5th common type of cancer worldwide and is considered as the 3rd common reason for cancer-related deaths. HCC often occurs on top of a cirrhotic liver. The prognosisis determined by several factors; tumour extension, alpha-fetoprotein(AFP) concentration, histologic subtype of the tumour, degree of liver dysfunction, and the patient's performance status. HCC prognosis is strongly correlated with diagnostic delay. To date, no ideal screening modality has been developed. Analysis of recent studies showed that AFP assessment lacks adequate sensitivity and specificity for effective surveillance and diagnosis. Many tumour markers have been tested in clinical trials without progressing to routine use in clinical practice. Thus, surveillance is still based on ultrasound(US) examination every 6 mo. Imaging studies for diagnosis of HCC can fall into one of two main categories: routine non-invasive studies such as US, computed tomography(CT), and magnetic resonance imaging, and more specialized invasive techniques including CT during hepatic arteriography and CT arterial portography in addition to the conventional hepatic angiography. This article provides an overview and spotlight on the different diagnostic modalities and treatment options of HCC.

原发性肝癌腹壁转移的介入治疗

目的探讨对原发性肝癌腹壁转移灶采用介入治疗的方法和疗效。方法对8例原发性肝癌腹壁转移患者行动脉插管灌注化疗、栓塞治疗,或经皮穿刺瘤内无水乙醇注射术。结果7例患者行动脉插管化疗栓塞术获得技术成功,术后5例患者腹壁转移灶内碘油沉积良好；2例患者部分瘤灶内碘油沉积不满意,行分次瘤体内无水乙醇注射术；1例患者动脉插管未能找到供血动脉,单纯采用经皮穿刺瘤体内无水乙醇注射。所有患者瘤灶处腹壁疼痛缓解或消失,3例腹壁体表肿块隆起者,肿块变小,变软。7例AFP升高患者,术后有不同程度下降。1例隆起肿块发生破溃、感染,其他患者未发生严重并发症。结论对原发性肝癌腹壁转移灶采用动脉插管灌注化疗、栓塞治疗,结合经皮穿刺瘤体内无水乙醇注射,对控制肿瘤生长、缓解疼痛,提高生存质量是可行方法之一。

无水乙醇瘤内注射治疗

目的：分析肝癌患者瘤内无水乙醇注射治疗（ＰＥＩＴ）疗效的影响因素，完善治疗技术。方法：１９９０～１９９５年，２３８例肝癌在超声引导下行瘤内无水乙醇行多点注射，包括肿瘤中央、周边及紧贴包膜外，至整个肿瘤均匀增强，每次注射１～２０ｍｌ，每周注射１～２次。结果：（１）无水乙醇注射即时，局部回声明显增强，稍后增强回声消退，消退速度与治疗次数有关。紧贴肿瘤包膜外注射时，回声呈环状增强。穿刺针穿入肿瘤的供应血管和引流血管时，局部回声改变不同。原肿瘤区的复发病灶，再次ＰＥＩＴ治疗时，乙醇常扩散困难；（２）病理显示癌细胞大部坏死，呈梯度改变，中央明显，外周坏死、变性相间。残留癌细胞周边多见，尤以大血管周围多见；（３）８例肿瘤原位复发快速增殖。结论：了解影响ＰＥＩＴ疗效因素，使用完善的治疗技术，定期随访，可产生良好的治疗效果。

乙酸经皮局部注射治疗小鼠肝癌的实验研究

使用两种浓度乙酸经皮局部注射治疗小鼠肝癌（Ｈ２２）。分别采用１５％、３０％浓度的乙酸进行瘤内注射硬化治疗，发现３０％浓度组效果更好，各浓度组均未发现对动物体的明显毒副作用，与无水乙醇治疗组相比无显著差异。提示在经皮局部注射治疗肝癌时，对无水乙醇不适合的患者。

B超引导下注射无水乙醇治疗肝癌34例疗效分析

作者采用在B超引导下经皮肝穿刺瘤内注射无水乙醇治疗肝癌34例,共43个病灶。其中原发性肝癌31例,继发性肝癌3例。肿瘤直径<3.0cm 30个,3.0-5.Ocm8个,5.0cm以上5个,治疗有效率分别为100％、75％和40％。术后半年、1年、3年生存率分别为73.5％、47％和11.7％。说明经皮肝穿刺瘤内注射无水乙醇法对肝癌,特别是小肝癌有较高的治疗应用价值。

B超引导下肝肿瘤无水乙醇注射的护理及并发症处理

目的探讨B超引导下肝肿瘤无水乙醇注射治疗患者的护理及并发症处理。方法对60例肝肿瘤患者实施B超引导下PEI,术前给予心理讲解,指导术中配合方法,术中密切监测病情变化,配合处理患者术中不适;术后根据患者情况给予一般护理、生命体征监测及并发症观察与处理。结果经过充分的术前准备,术中观察及术后护理,所有接受治疗患者均可耐受PET,未出现严重并发症。结论护士周到的术前准备,细致而精确地术中配合及术后严密的安抚观察,是PEI成功治疗肝肿瘤不可缺少的一环。

60例CT引导下化学消融治疗肝脏恶性肿瘤的技术探讨

目的:探讨CT引导下化学消融(PEI)治疗肝癌的一些技术细节问题。方法:对45例原发性肝癌(含小肝癌9例),15例转移性肝癌,共计92个瘤体,CT引导下化学消融治疗116次(其中对8例膈下肝癌采用经皮-肺-膈肌途径化学消融)。结果:AFP降至正常者15例;AFP不同程度下降者21例;AFP未下降或上升者9例。在术后3个月经超声CDFI随访的92个瘤体中,51个经治瘤体表现为CDFI血流信号消失,41例表现为肿瘤类或周边点状血流信号;结合同期其他影像学检查评价,35个经治瘤体缩小;45个经治瘤体停止增长,12例肿瘤周边复发或出现新的转移灶。在肿瘤基质纤维化不明显的条件下,使用三测孔笔尖式注射针,与斜面穿刺针相比无优势。结论:PEI技术使用中,无水乙醇弥散程度与TACE后肿瘤坏死程度正相关,与肿瘤本身纤维化的程度负相关;肿瘤基质纤维化程度重则不推荐PEI。多普勒CDFI靶区血流信号评价对PEI重点消融部位的判断和治疗方式的选择有一定的参考价值。

超声引导乙醇消融治疗原发性肝癌的临床研究

目的:探讨超声引导下无水乙醇消融治疗原发性肝癌的疗效。方法:应用彩色多普勒超声引导经皮肝内肿瘤穿刺注射无水乙醇治疗原发性肝癌24例,按肿瘤直径每1.0 cm注入乙醇1.5~2.0 mL计算注射量,每周1~2次,4~6次为1个疗程。结果:甲胎蛋白(AFP)4例转阴,10例下降50%以上;治疗3个月后彩超及CT复查,4例肿瘤完全消失,16例肿瘤均有不同程度缩小,总有效率83.3%。1年生存率79.2%,2年生存率66.7%。结论:超声引导乙醇消融治疗早期原发性肝癌局部疗效较好,费用低廉,安全实用。

二期手术切除为主综合治疗中晚期肝癌36例体会

目的 探讨二期手术切除为主综合治疗中晚期肝癌的效果。方法 回顾我院 1993年 4月～ 2 0 0 1年 3月收治的二期手术切除的中晚期肝癌患者 3 6例 ,术前均行经皮股肝动脉化疗栓塞 (TACE) ,2 3例术前行B超引导下无水酒精瘤体内注射 (PEI) ,本组 3 6例术中均行经胃十二指肠动脉置管至肝动脉 ,18例经胃网膜右静脉置管至门静脉 ,皮下埋植化疗药泵 ,术后区域化疗。结果 以寿命表法计算 1、2、3、4、5年累计生存率 ,分别为 83 3 3 %、69 44 %、65 5 5 %、5 5 5 5 %、47 2 2 % ,中位生存期 3 2 5个月。结论 积极的综合法疗可延长中晚期肝癌患者生存期 ,延迟复发 。

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.

肝动脉化疗栓塞联合超声介入治疗非手术肝癌的临床观察

目的 观察肝动脉化疗栓塞 (TACE)联合超声介入 (多电极射频或经皮穿刺乙醇注射 )治疗原发性肝癌的临床疗效。方法 32 6例原发性肝癌患者分别行TACE、超声介入治疗 ,并与同期TACE联合超声介入治疗进行比较。结果 联合治疗组的近期疗效、甲胎蛋白下降均优于单纯TACE或超声介入治疗组 ,其副作用发生依次为TACE >TACE +联合超声介入 >超声介入。

经皮微波消融结合温度监测及无水乙醇注射治疗近胃肠道肝细胞癌的疗效评估

目的：观察经皮微波消融结合温度监测及无水乙醇注射治疗近胃肠道肝细胞癌的临床疗效。方法选取新郑市人民医院收治的近胃肠道肝细胞癌（肿瘤与胃肠道距离≤5 cm）患者68例（88个肿瘤）作为观察组，取同期收治的近胃肠道肝细胞癌患者60例（81个肿瘤）作为对照组，均在温度监测下行经皮微波消融治疗，观察组于近胃肠道边缘肿瘤组织内注射无水乙醇，对照组不予以处理。记录两组治疗前及治疗后1、3个月血清甲胎蛋白（ AFP）水平变化情况；记录肿瘤消融率和并发症发生率；随访12～17个月，了解两组病死率、复发率及肝内转移率。结果观察组肿瘤完全消融率为91.18％，显著高于对照组的64.71％，观察组治疗1、3个月血清甲胎蛋白（ AFP）水平分别为（158.41±18.33）、（57.59±11.26）μg／L，均显著低于对照组，差异有统计学意义（P＜0．05）。随访12～17个月，观察组病死率和肝内转移率分别为17.71％、13.24％，显著低于对照组的30.0％、28.33％，差异有统计学意义（ P＜0.05）。结论温度监测下经皮微波消融联合无水乙醇注射治疗近胃肠道肝细胞癌，有利于提高肿瘤完全消融率。