Treatment of hepatocellular carcinoma.

Treatment options have largely been selected according to empirical criteria, such as the presence or absence of cirrhosis, number and size of tumors, and degree of hepatic deterioration and taking into account the local technological and economic resources. There are virtually no controlled studies comparing the efficacy of the available treatments, and the substantial heterogeneity of survival between control groups does not allow us to obtain therapeutic evaluation by comparing results of separate trials. The reassessment of treatment outcomes on the basis of intention-to-treat analysis yielded less encouraging figures. Hepatic resection is the primary option for the few patients with a hepatocellular carcinoma arising in a normal liver with well-preserved hepatic function and for patients with a single tumor, compensated cirrhosis and low portal hypertension who are not candidable to liver transplantation. The latter is the best treatment modality for patients with a solitary tumor <5 cm in diameter or patients with less than three tumors <3 cm, resulting in a 5-year survival of 75%. Locoregional ablative treatments are curative options for patients with a "resectable" tumor who cannot be offered transplantation or hepatic resection. The 5-year survival is approximately 50% but it copes with a high risk of tumor recurrence. Patients with advanced tumor disease cannot be offered curative treatments but only symptomatic treatments.     

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.     

介入治疗在提高中晚期肝癌二期切除率中的疗效及意义

目的探讨中晚期原发性肝癌（HCC）经门静脉、肝动脉双重介入治疗使肿瘤缩小后切除的疗效及意义。方法30例中晚期肝癌患者（肿瘤直径8．0～20．0cm，平均10．2cm）在超声引导下行门静脉化疗及经皮穿刺肝动脉化疗栓塞（TACE），观察肝功能，AFP，各肝叶体积及不良反应，并择期手术切除肿瘤。结果手术前肿瘤平均直径缩小至4．9cm，末次TACE距手术时间为1～3个月，平均1．6个月。25例AFP阳性中9例转正常。30例患者中，行肝段、联合肝段或肝部分切除25例，左半肝切除4例，左外叶切除1例。切除肿瘤中各有60％～100％坏死，其中12例100％坏死。1、3、5年生年率分别为80％、68％、59％。结论术前经门静脉、肝动脉双重介入治疗可为一期不能切除的中晚期肝癌患者提供二期手术机会，提高手术的安全性，对预防转移、延迟复发、改善预后有肯定意义。     

尾状叶与非尾状叶肝癌手术切除疗效对比观察

目的：比较尾状叶肝细胞癌与非尾状叶肝细胞癌手术切除治疗效果的差异,为提高肝细胞癌的手术切除治疗效果提供临床依据。方法选择该院2008年7月-2013年10月42例尾状叶肝细胞癌切除术患者作为研究对象,并选择同期42例非尾状叶肝细胞癌患者作为对照。对两组患者的临床病理学特征、手术情况、术后复发率及生存期进行比较分析。结果尾状叶肝细胞癌患者有较长的手术时间（平均192．9 min vs 128．7 min）、较长的血管阻断时间（平均32．5 min vs 24．7 min）、较多的术中出血（平均为827．6 mL vs 431．4 mL）,两组的并发症发生率没有显著差异（28．6％vs 21．4％）。两组患者均无院内死亡。尾状叶肝细胞癌组中位随访期为42．3个月,复发率为56．7％;非尾状叶肝细胞癌组中位随访期为43．3个月,复发率为41％。两组患者肿瘤复发率差异具有统计学意义,在肿瘤复发模式上无显著差异。尾状叶肝细胞癌患者1、3、5年总生存率分别为73．8％、51．9％和28．3％,对照组分别为84．2％、71．5％和49．2％（P＝0．0001）。尾状叶肝细胞癌患者1、3、5年无瘤生存率分别为60．9％、33．8％和17．6％,对照组为72．9％、60．3％和41．7％（P＝0．0012）。两组患者总生存率与无瘤生存率差异显著。结论手术切除治疗尾状叶肝细胞癌与非尾状叶肝细胞癌有着显著不同的疗效,其可能原因与尾状叶肝细胞癌手术切缘不足、术中较多出血等有关。     

Liver transplantation for hepatocellular carcinoma: current role and future opportunities

Hepatocellular carcinoma (HCC) is the most common primary malignancy of the liver. It represents the fifth most common cancer worldwide, and one whose incidence is on the rise. Liver cancer is the third most common cause of cancer mortality globally and thus a major health concern worldwide. Therapeutic options for this tumor include surgical resection, local ablative therapies, and systemic treatment. Liver transplantation has emerged as a highly effective treatment for patients with HCC, particularly in the setting of significant underlying liver disease. Current protocols in transplantation for this tumor utilize strict size criteria and staging (TNM classification) to select patients for this therapy. Selection criteria for liver transplantation for HCC that are accepted in the U.S. include: 1 tumor < 5cm, no greater than three tumor nodules, each less than 3cm in diameter 3) no macroscopic invasion of blood vessels or lymph nodes, and no extra-hepatic spread of tumor. Eligibility criteria and immunosuppression strategies are continuing to evolve in this field. Nonetheless, in appropriately selected patients, liver transplantation may provide a cure for HCC with survival rates equal to that of liver transplantation for end-stage liver disease (ESLD) from other causes. Liver transplantation has been established as one of the principal treatment modalities for this difficult disease.     

Review article: liver transplantation for HCC. Treatment options on the waiting list

The most widely adopted criteria to admit and maintain patients with HCC and cirrhosis in the waiting list for liver transplantation are the Milano criteria, consisting in the presence of a single tumour 相似文献   

肝切除术治疗原发性肝癌：附588例临床分析

对1959年9月～1993年4月行肝癌肝切除588例进行回顾，第一阶段（1959年9月～1985年12月）施行传统肝切除术142例，均为直径＞5cm中晚期肝癌，手术死亡率11％，术后3年和5年生存率分别为18％、7％。第二阶段（1986年1月～1993年4月）行肝癌肝切除术446例，以肝段切除及癌肿局部切除为主，采用多种技术改良及高新医疗设备，并予以化疗、免疫治疗等综合措施，手术死亡率＜2％，术后1年、3年、5年生存率分别为89％、55％、26％。     

原发性肝癌合并门静脉癌栓肝移植术后27例随访报告

目的 探讨肝移植治疗原发性肝癌合并门静脉癌栓的价值。方法 收集我院2000年9月至2005年1月进行的27例原发性肝癌合并门静脉癌栓肝移植病例的临床资料并进行分析。结果 本组6个月、1年、2年生存率分别为79．2％、57．1％、51．4％，存活时间最长达46个月，6个月、1年和2年的无瘤生存率为58.3％、37．1％及37．1％。结论 如果没有肝外远处转移，肝移植治疗原发性肝癌合并门静脉癌栓是一种有效的姑息治疗方式。     

外生型肝癌的诊治

目的探讨外生型肝癌的诊断和治疗。方法回顾分析23例外生型肝癌的临床资料。结果肿瘤位于肝左叶7例,右叶16例,均有完整包膜,肿瘤最大直径4～35cm,平均16．2cm。外生型肝癌的诊断主要依靠临床表现、AFP、CT、MAI、肝功脉造影及病理进行综合诊断。外生型肝癌易误诊。常侵犯周围组织和器官并形成新的血液供应网。1、3、5年生存率分别为87％、78．2％、56．5％。结论外生型肝癌治疗方法首选手术切除,其手术切除率高、预后较好。     

Surgical management of hepatocellular carcinoma

Hepatocellular carcinoma is the sixth most common cancer worldwide and its incidence is rising in Western countries. Liver resection is the treatment of choice in noncirrhotic patients and in cirrhotic patients with well-preserved liver function. Postresection survival rates are in the range of 41-74% at 5 years. Predictors of recurrence include tumor grade, vascular invasion, tumor size, number of tumors, presence of satellites, alpha-fetoprotein level, transfusion, and positive surgical margin. Second hepatic resection for recurrent hepatocellular carcinoma is applicable in about 15% of patients with recurrence. Liver transplantation has become an important element of the therapeutic strategy for hepatocellular carcinoma. Liver transplantation provides excellent outcomes applying the Milan criteria with 5-year survival rates of 70% and low recurrence rates. Intention-to-treat analysis has shown that wide extended indications lead to 25% 5-year survival rates. Expansion of indications beyond the Milan Criteria and use of bridging/downstaging procedures, to convert intermediate advanced stages of hepatocellular cancer within the Milan criteria limits, are counterbalanced by graft shortage and increasing use of marginal donors. Living donor transplantation is an alternative that can eliminate the waiting time and the attendant risk of drop-out.     

Hepatocellular carcinoma (HCC): current and evolving therapies

Hepatocellular carcinoma (HCC) is associated with a historical 5-year survival rate of less than 5%. Evidence suggests that the incidence of HCC is rising in several countries, including the US. Current curative treatment options for HCC include surgical resection and liver transplantation, but these approaches are restricted to carefully selected patients who may benefit from such interventions. Other curative options include ablative therapies, which destroy tumor cells via the injection of chemical substances, radiation, or heating or cooling. Patients with more advanced HCC may be candidates for noncurative treatments, including transarterial embolization and transarterial ablative therapy with beads impregnated with radiation-emitting substances - if the tumor has not invaded vessels or disseminated outside the liver. New therapeutic approaches include Raf kinase inhibitors, such as sorafenib. Other treatments under investigation include immunotherapy, tyrosine kinase receptor inhibitors, and treatments arising from technical advances in ablation and radiation. These new approaches may help to address the enormous need for expanded treatment options for patients with HCC.     

Survival after treatment with curative intent for hepatocellular carcinoma among patients with vs without non‐alcoholic fatty liver disease

Background

Non‐alcoholic fatty liver disease (NAFLD) is expected to become a leading aetiology of hepatocellular carcinoma (HCC)‐related mortality in the United States. HCC treatments with curative intent (OLT, orthotopic liver transplantation; resection; RFA, radiofrequency ablation) can improve survival in carefully selected patients.

Aim

To compare survival after receipt of curative treatment for NAFLD and non‐NAFLD‐HCC aetiologies (HCV, chronic hepatitis C; HBV, chronic hepatitis B; ALD, alcoholic liver disease) and by treatment was performed.

Methods

A cohort of 17 664 patients was assembled using linked Surveillance, Epidemiology, and End Results and Medicare data from 1991 to 2011 with confirmed diagnosis of HCC.

Results

The cohort was mostly male, aged 70 (21‐106) years, without cardiovascular disease, and had liver cirrhosis without decompensation, metastatic HCC or large tumour size (>5 cm). The NAFLD‐HCC group was mostly female and older with more cardiovascular disease, metastatic HCC, and large tumour size and less cirrhosis and decompensated liver disease than the non‐NAFLD‐HCC groups. The NAFLD group was 47% less likely to receive any curative treatment as compared with non‐NAFLD aetiologies (OR 0.53, P < .001). NAFLD‐HCC had worse median survival after OLT (3.2, 0‐12.9 years, P = .01) but had improved survival after resection (2.4, 0‐12.0 years, P < .001) as compared with non‐NAFLD‐HCC. No significant survival differences existed for RFA by HCC aetiology. NAFLD was not an independent predictor of mortality after OLT, resection or RFA.

Conclusion

Patients with NAFLD‐HCC had worse survival after OLT but favourable survival after resection, particularly in the absence of cirrhosis, as compared with non‐NAFLD‐HCC aetiologies.

     

Liver stiffness measurement by magnetic resonance elastography is not associated with developing hepatocellular carcinoma in subjects with compensated cirrhosis

Aliment Pharmacol Ther 2011; 34: 83–91

Summary

Background Liver stiffness assessed using transient elastography is described as a potential risk factor for hepatocellular carcinoma (HCC) in cirrhosis. However, the strict assessment of hepatic parenchymal areas uninvolved with HCC has not been investigated. Aim To determine if liver stiffness of nonmalignant hepatic parenchyma using magnetic resonance elastography (MRE) is higher in patients with HCC compared with controls. Methods Cases were defined by compensated cirrhosis with a Child–Turcotte–Pugh score <7 and HCC by radiological criteria or histology. Control subjects with compensated cirrhosis were frequency matched with cases by gender and disease aetiology. Overt manifestations of portal hypertension and previous therapy for liver disease or HCC were exclusion criteria. Region of interest analyses were performed on hepatic parenchyma regions distant to HCC location among cases. Results Thirty patients with HCC and 60 matched controls comprised the study cohort. The mean age for cases was 64 ± 10 years (range, 45–85) with 70% being men. Major disease aetiologies were chronic viral hepatitis (57%), non‐alcoholic fatty liver disease (33%) and alcohol (10%). Twenty‐eight (93%) patients had solitary HCC lesions with a mean size of 5.2 cm (range, 2–14 cm). However, patients with HCC had similar liver stiffness among uninvolved areas distant to HCC lesions, when compared with controls without HCC (mean, 6.1 ± 2.0 vs. 6.3 ± 2.5 kPa, P = 0.7). Conclusion In contrast to previous studies with transient elastography, we did not observe a systematic association between liver stiffness assessed using MRE and the presence of HCC in patients with compensated cirrhosis.     

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.     

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。     

射频消融与手术治疗小肝癌的疗效比较

目的 探讨原发性小肝癌手术切除治疗与射频消融治疗的疗效.方法 将60例原发性小肝癌患者分为两组,每组30例.A组采用射频消融治疗;B组采用手术切除.术后均行常规化疗.比较两组术后5年肝癌复发率和生存率.结果 A组患者5年肝癌复发率为13.3%、5年生存率为93.3%;B组患者5年肝癌复发率为16.7%、5年生存率为90.0%.两组比较,差异均无统计学意义(P>0.05).结论 在早期诊断的原发性小肝癌,局部射频消融治疗术与手术切除治疗效果相当;但局部射频消融治疗创伤小,是治疗早期原发性小肝癌的有效方法.     

Review article: the modern diagnosis and therapy of cholangiocarcinoma

Cholangiocarcinomas are epithelial neoplasms that originate from cholangiocytes and can occur at any level of the biliary tree. They are broadly classified into intrahepatic tumours, (extrahepatic) hilar tumours and (extrahepatic) distal bile duct tumours. In spite of well-understood predispositions, most cholangiocarcinomas arise in the absence of risk factors. In suspected cases, the diagnosis can be established with non-invasive imaging studies. Biliary invasion should be reserved for patients with obstruction. In high-risk patients, advanced cytological tests of aneuploidy (digital image analysis and fluorescent in situ hybridization) aid early diagnosis. In the absence of primary sclerosing cholangitis, curative surgical resection has 5-year survival rates of 2-43%, higher survival observed in patients with clear surgical margins and concomitant hepatic resection for hilar tumours. Patients with unresectable cholangiocarcinoma or pre-existing primary sclerosing cholangitis should be considered for liver transplantation with neoadjuvant chemoirradiation, in specialized centres.     

Current management of cholangiocarcinoma

Cholangiocarcinoma is the second most common primary hepatobiliary malignancy after hepatocellular carcinoma and remains among the most difficult management problems faced by surgeons. Curative surgery is achieved in only 25% to 30% of patients. Local tumor extent, such as portal vein invasion and hepatic lobar atrophy, does not preclude resection. Long-term survival has been seen only in patients who underwent extensive liver resections, suggesting that bile-duct excision alone is less effective. The majority of patients have unresectable disease, with 20% to 30% incidence of distant metastasis at presentation. Unresectable patients should be referred for nonsurgical biliary decompression, and in potential curative resection candidates the use of biliary stents should be reduced. Liver transplantation provides the option of wide resection margins, expanding the indication of surgical intervention for selected patients who otherwise are not surgical candidates due to lack of functional hepatic reserve.     

Combination adjuvant chemotherapy with oxaliplatin, 5-fluorouracil and leucovorin after liver transplantation for hepatocellular carcinoma: a preliminary open-label study

The purpose of this study was to evaluate the efficacy of postoperative adjuvant chemotherapy with FOLFOX regimen on the outcome after LT for HCC patients who did not meet the Milan criteria. Ninety-five consecutive HCC patients with liver cirrhosis undergoing LT were enrolled. Fifty-eight who did not meet the Milan criteria were randomized to open-label treatment with or without adjuvant chemotherapy after LT (n = 29/group). The FOLFOX chemotherapy protocol comprised 3-week cycles of oxaliplatin 100 mg/m² on day 1, leucovorin (calcium folinate, CF) 200 mg/m² on day 1 followed by 3-day, and 5-fluorouracil (5-FU) 2000 mg/m² as a 48-h continuous infusion, for up to six courses in the 1st year after transplantation. Median survival was extended by 4.57 months by combination chemotherapy. The 1- and 3-year survival rates were 89.7% and 79.3% with chemotherapy versus 69.0% and 62.1% without chemotherapy. The cumulative 1-year survival was significantly increased by chemotherapy (log-rank test, P = 0.043). The 6-month tumor-free survival rate was 24.1% higher with chemotherapy than without. The recurrence rate after LT was significantly different between the two groups at 6 months (P = 0.036), but not at 3 years (P = 0.102). The chemotherapy regimen was generally well tolerated. Post-LT adjuvant chemotherapy with oxaliplatin/5-FU/CF could not prevent tumor recurrence post-LT but may contribute to improve the survival of HCC patients who do not meet the Milan criteria. These results should be verified in a larger sample with a longer follow-up period.     

肝门部胆管癌的外科治疗探讨

目的综合分析肝门部胆管癌的不同的手术方式及其远期疗效,探讨影响肝门部胆管癌的手术方式的选择及疗效的相关因素。方法回顾重庆市九龙坡第二人民医院治疗112例肝门部胆管癌的纪录,分析切除率、并发症及病死率等,并综合文献进行讨论。结果根治性切除手术难度大,甚至联合肝切除亦难以达到根治目的,根治性切除率只有43.7%。随访72例中,根治切除者1、2、3年生存率分别为62.2%、33.6%、13.4%;姑息切除者1、2年生存率为54.3%、13.3%,无3年生存者;非切除性胆管内、外引流者1、2年生存率为26.2%、12.1%,无3年生存者。结论肝门部胆管癌的治疗仍以手术切除为主,只有根治性切除才能获得最佳疗效,联合肝叶、血管、淋巴结等切除的扩大根治术可延长患者生存期。