Appropriate treatment strategies improve survival of hepatocellular carcinoma patients with portal vein tumor thrombus

AIM:To evaluate the survival benefits of different treatment strategies for hepatocellular carcinoma(HCC)patients with portal vein tumor thrombus(PVTT)and to determine the prognosis factors.METHODS:Between 2007 and 2009,338 HCC patients treated for PVTT were retrospectively studied.The patients were divided into 4 groups that underwent different treatments:the conservative treatment group(n=75),the transarterial chemoembolization(TACE)group(n=86),the hepatic resection group(n=90),and the hepatic resection associated with postoperative TACE group(n=87).Survival rates were determined using the Kaplan-Meier method and differences between the groups were identified through log-rankanalysis.Cox’s proportional hazard model was used to identify the risk factors for survival.RESULTS:The mean survival periods for patients in the conservative treatment,TACE,hepatic resection and hepatic resection associated with postoperative TACE groups were 3.8,7,8.2 and 15.1 mo,respectively.Significant differences were observed in the survival rates.For the surgical resection associated with postoperative TACE group,the survival rates after 1,2 and3 years were 49%,37%and 19%,respectively.These results were significantly higher than those of the other groups(P<0.05).Meanwhile,the 1,2 and 3 year survival rates for the surgical resection group were 28%,20%and 15%,whereas those for the TACE group were17.5%,0%and 0%,respectively.These values significantly increased after hepatic resection compared with those after TACE(P<0.05).CONCLUSION:Surgical resection is the most effective therapeutic strategy for HCC patients with PVTT and results in high hepatic functional reserve.For patients who can tolerate the procedure,postoperative TACE is necessary to prevent recurrence and prolong the survival period.     

Comprehensive treatments for hepatocellular carcinoma with tumor thrombus in major portal vein

AIM: To evaluate the efficacy of transcatheter arterial chemoembolisation(TACE) compared with surgical intervention and sorafenib for treatment of hepatocellular carcinoma(HCC) in patients with tumor thrombus extending to the main portal vein.METHODS: From 2009 to 2013, a total of 418 HCC patients with tumor thrombus extending to the main portal vein were enrolled in this study and divided into four groups. These groups underwent different treatments as follows: TACE(n = 307), surgical intervention(n = 54), sorafenib(n = 15) and palliativetreatment(n = 42). Overall survival rates were determined by Kaplan-Meier method, and differences between the groups were identified through log-rank analysis. Cox's proportional hazard model was used to identify the risk factors for survival.RESULTS: The mean survival periods for patients in the TACE, surgical intervention, sorafenib and palliative treatment groups were 10.39, 4.13, 5.54 and 2.82 mo, respectively. For the TACE group, the 3-, 6-, 12-and 24-mo survival rates were 94.1%, 85.9%, 51.5% and 0.0%, respectively. The corresponding rates were 60.3%, 22.2%, 0.0% and 0.0% for the surgical intervention group and 50.9%, 29.5%, 0.0% and 0.0% for the sorafenib group. Evidently, the results in the TACE group were significantly higher than those in the other groups(P 0.0001). Furthermore, no significant difference among survival rates was observed between TACE with/without sorafenib(10.22 mo vs 10.52 mo, P = 0.615). No significant difference in survival rates was also found among the surgical intervention, sorafenib and palliative treatment groups(P 0.05). These values significantly increased after TACE with/without sorafenib compared with other treatments(P 0.05).CONCLUSION: For HCC patients with tumor thrombus extending to the main portal vein, TACE can yield a higher survival rate than surgical intervention or sorafenib treatment.     

Surgical treatment for advanced hepatocellular carcinoma with portal vein tumor thrombus

The Barcelona Clinic Liver Cancer staging system recommends a tyrosine kinase inhibitor (sorafenib) as standard therapy in advanced hepatocellular carcinoma (HCC) patients with portal vein tumor thrombus (PVTT). Sorafenib has been shown to prolong median overall survival (OS) by approximately 3 months in advanced HCC patients with PVTT (8.1 vs. 4.9 months). However, its clinical effectiveness is still controversial and standard treatment with sorafenib is not established in Japan. Surgical resection is considered a potentially curative treatment and provides an acceptable outcome for carefully selected patients. The surgical mortality rate in patients with PVTT who receive surgical resection ranges from 0% to 10%. The median survival time and 1-year OS rate in HCC patients with PVTT who undergo surgical resection have been found to range from 8 to 22 months and 21.7% to 69.6%, respectively. But improvement in therapeutic outcome is difficult with surgical treatment alone. Combination treatment in conjunction with such methods as transarterial chemoembolization, hepatic artery infusion chemotherapy, and radiotherapy has been found to improve the prognosis (median survival time, 11.5–37 months; 1-year OS rate, 46.8–100%). Yet, many problems remain, such as surgical indications and surgical techniques. After resolving these points, a multidisciplinary strategy based on surgical treatment should be established for advanced HCC with PVTT.     

肝细胞癌伴门静脉癌栓的降期治疗

肝细胞癌伴门静脉癌栓发生率高,病情进展快,现有治疗方法有限且效果不佳。虽然国外指南推荐索拉非尼为唯一治疗手段,但临床研究显示部分患者,尤其是伴癌栓侵犯至门静脉一级或二级分支的患者(程氏分型Ⅰ/Ⅱ型),通过手术切除可以取得比其他非手术疗法更好的效果。然而临床实践中相当一部分患者由于病灶范围较广无法根治性切除,或者由于癌栓侵犯到门静脉主干(程氏Ⅲ型),术后癌栓残留可能性高,需要通过降期切除的方法改善预后。研究发现通过新辅助三维适形放疗、经肝动脉钇-90微球放射性栓塞、肝动脉灌注化疗等姑息性治疗方法,部分患者(5.7%~26.5%)可出现门静脉癌栓消退乃至消失、肿瘤体积缩小、卫星灶消失等现象,从而使病灶降期,提高手术切除率并延长患者生存时间。多学科综合治疗对于进一步提高肝细胞癌伴门静脉癌栓患者的降期切除率至关重要。     

Clinical significance of removal of tumor thrombi in the main portal vein in patients with hepatocellular carcinoma

Twenty-two patients with portal vein tumor thrombi secondary to hepatocellular carcinoma were studied to evaluate the effectiveness of diagnostic and treatment procedures. B-mode ultrasonography is a simple and accurate means for the detection of tumor thrombus in the portal vein. All of the 22 patients were correctly diagnosed by this method, which should be used as the initial screening procedure in such patients. Fourteen of the 22 patients underwent surgical procedures, including embolectomy from the portal trunk; removal of the tumor thrombi combined with hepatectomy or through the rechanneled umbilical vein; and operative transcatheter arterial chemotherapy. The other 8 patients were treated by transcatheter arterial embolization or were not treated. The surgical treatment effectively prevented acute variceal bleeding in the patients who underwent the procedures successfully. The mean value of the portal venous pressure was reduced from 46 cmH₂O to 32 cmH₂O after the surgery. As a result of the effective portal decompression, the patients in the surgical group had a better prognosis and longer mean survival than the others. Our study suggests that portal vein tumor thrombus is not an absolute contraindication for surgery, and that accurate detection and prompt treatment are the keys to the achievement of better clinical results.     

Treatment of hepatocellular carcinoma in patients with portal vein tumor thrombosis: Beyond the known frontiers

Hepatocellular carcinoma is one of the most frequent malignant tumors worldwide:Portal vein tumor thrombosis(PVTT)occurs in about 35%-50%of patients and represents a strong negative prognostic factor,due to the increased risk of tumor spread into the bloodstream,leading to a high recurrence risk.For this reason,it is a contraindication to liver transplantation and in several prognostic scores sorafenib represents its standard of care,due to its antiangiogenetic action,although it can grant only a poor prolongation of life expectancy.Recent scientific evidences lead to consider PVTT as a complex anatomical and clinical condition,including a wide range of patients with different prognosis and new treatment possibilities according to the degree of portal system involvement,tumor biological aggressiveness,complications caused by portal hypertension,patient’s clinical features and tolerance to antineoplastic treatments.The median survival has been reported to range between 2.7 and 4 mo in absence of therapy,but it can vary from 5 mo to 5 years,thus depicting an extremely variable scenario.For this reason,it is extremely important to focus on the most adequate strategy to be applied to each group of PVTT patients.     

Usefulness of staging systems and prognostic scores for hepatocellular carcinoma treatments

Therapeutic management of hepatocellular carcinoma(HCC) is quite complex owing to the underlying cirrhosis and portal vein hypertension. Different scores or classification systems based on liver function and tumoral stages have been published in the recent years. If none of them is currently "universally" recognized, the Barcelona Clinic Liver Cancer(BCLC) staging system has become the reference classification system in Western countries. Based on a robust treatment algorithm associated with stage stratification, it relies on a high level of evidence. However, BCLC stage B and C HCC include a broad spectrum of tumors but are only matched with a single therapeutic option. Some experts have thus suggested to extend the indications for surgery or for transarterial chemoembolization. In clinical practice, many patients are already treated beyond the scope of recommendations. Additional alternative prognostic scores that could be applied to any therapeutic modality have been recently proposed. They could represent complementary tools to the BCLC staging system and improve the stratification of HCC patients enrolled in clinical trials, as illustrated by the NIACE score. Prospective studies are needed to compare these scores and refine their role in the decision making process.     

Efficacy of combination therapy with transcatheter arterial chemoembolization and radiofrequency ablation for intermediate-stage hepatocellular carcinoma

Abstract

Objectives: Transcatheter arterial chemoembolization (TACE) is the standard therapy for patients with intermediate-stage hepatocellular carcinoma (HCC). This study aimed to determine whether combination therapy with radiofrequency ablation (RFA) and TACE was superior to TACE monotherapy for intermediate-stage HCC and identify cases in which this technique was the most effective.

Materials and methods: We selected patients with intermediate HCC who met the following eligibility criteria: (1) ≥ 20 years of age, (2) receiving initial therapy, (3) ≤7 tumors, and (4) maximum tumor diameter <5?cm. We performed propensity score matching (PSM) using potential confounding factors. We retrospectively compared the cumulative overall survival rate and recurrence-free survival rate between the TACE?+?RFA and TACE groups. Additionally, a sub-group analysis was performed for preoperative factors.

Results: Among the 103 patients, 92 were selected using PSM. The cumulative overall survival rates at 1, 3, and 5 years for the TACE?+?RFA group were 97.4%, 70.4%, and 60.4%, respectively, which were significantly higher than those for the TACE group (92.7%, 55.7%, and 22.8%, respectively, p?=?.045). The recurrence-free survival rates at 0.5, 1, and 2 years for the TACE?+?RFA group were 80.0%, 58.6%, and 33.3%, respectively, which were significantly higher than those for the TACE group (34.5%, 8.8%, and 2.9%, respectively, p?p?=?.036).

Conclusions: The addition of RFA to TACE improved cumulative overall and recurrence-free survival in patients with intermediate-stage HCC, especially in patients with AFP <100.     

Transarterial embolization and low-dose continuous hepatic arterial infusion chemotherapy with oxaliplatin and raltitrexed for hepatocellular carcinoma with major portal vein tumor thrombus

AIM To determine the efficacy and safety of transarterial embolization and low-dose continuous hepatic arterial infusion chemotherapy with oxaliplatin and raltitrexed in hepatocellular carcinoma(HCC) with major portal vein tumor thrombus(MPVTT).METHODS eighty-six patients with MPVTT accepted routine embolization. The catheter was kept in the hepatic artery and oxaliplatin(50 mg in 250 m L of glucose) was infused by pump for 4 h,followed by raltitrexed(2 mg in 100 m L of 0.9% saline) infusion by pump for the next 1 h. The efficacy and safety were evaluated afterthe transarterial chemoembolization(TACe).RESULTS Full or partial embolization was achieved in 86 cases,where all the cases received low dose continuous hepatic arterial infusion chemotherapy. Complete responses(CRs),partial responses(PRs),stable disease(SD),and disease progression(PD) for intrahepatic disease were observed in 0,45,20,and 21 patients,respectively. The 1-,2-and 3-year overall survival rates of the 86 patients were 40.7%,22.1%,and 8.1% respectively,and the median survival time was 8.7 mo. Complication was limited. CONCLUSION TACE with low dose continuous hepatic arterial infusion of oxaliplatin and raltitrexed could be an option in MPVTT patient; it was shown to be effective in patients with advanced HCC with MPVTT with less toxicity.     

Reappraisal of repeated transarterial chemoembolization in the treatment of hepatocellular carcinoma with portal vein invasion

Background and Aim:  This study aimed to evaluate the therapeutic efficacy and safety of repeated transarterial chemoembolization (TACE) with additional radiation therapy (RT) in hepatocellular carcinoma (HCC) with portal vein (PV) invasion.
Methods:  We performed survival analysis of consecutive HCC patients with PV invasion according to the treatment modalities after stratification by the degree of PV invasion and liver function retrospectively.
Results:  During 2005, 281 patients were newly diagnosed to have HCC with PV invasion at our institution. Repeated TACE or transarterial chemoinfusion (TACI) was performed in 202 (71.9%) patients and additional RT was performed for PV invasion in 43 of them. A total of 281 patients had a median survival of 5.2 months and a 2-year survival rate (YSR) of 19.2%. Repeated TACE showed significant survival benefits compared with conservative management in patients with PV branch invasion; median survival and 2-YSR was 10.2 vs 2.3 months and 33.7% vs 0% in Child–Pugh A categorized patients and 5.5 vs 1.3 months and 10.3 vs 0% in Child–Pugh B categorized patients, respectively ( P  < 0.001). In patients with PV branch invasion, the survival rate was significantly longer with TACE/TACI plus RT than with TACE/TACI alone both in Child–Pugh A categorized patients (1-YSR: 63.6 vs 35.6%, P  = 0.031) and Child–Pugh B categorized patients (1-YSR: 66.7 vs 7.7%, P  = 0.007). Repeated TACE was well tolerated in our patients, with only one dying within one month after TACE.
Conclusion:  Repeated TACE with additional RT can be performed safely and showed a significant survival benefit in HCC patients with PV branch invasion with conserved liver function.     

经肝动脉化疗栓塞术治疗肝细胞癌合并门静脉癌栓的预后影响因素分析

目的评估肝细胞癌(HCC)合并门静脉癌栓患者经肝动脉化疗栓塞术(TACE)治疗后的效果及影响预后的因素。方法回顾性分析2006年1月-2010年12月第四军医大学西京医院收治的152例行TACE治疗的HCC合并门静脉癌栓患者的临床资料。观察TACE术后肝衰竭、上消化道大出血、栓塞后综合征等发生情况,分析生存期资料与影响预后的因素。Kaplan-Meier法计算累积生存率,采用Log-Rank法进行单因素分析,Cox比例风险模型进行多因素分析。结果患者中位生存时间为5.0(95%可信区间:4.4~5.6)个月,6、12、18个月的累积生存率分别为37%、18%和9%。单因素分析显示肿瘤大小、肿瘤类型、肝两叶累及、远处转移和Child-Pugh分级是HCC合并门静脉癌栓患者行TACE治疗预后的影响因素(χ2值分别为5.108、11.542、6.036、12.319、22.574,P值均0.05);多因素分析显示肿瘤大小、肿瘤类型、远处转移和Child-Pugh分级是影响患者预后的独立危险因素(Wald值分别为11.243、5.021、7.651、25.876,P值均0.05);而HCC合并门静脉癌栓患者发生肝衰竭的唯一影响因素是Child-Pugh分级(P=0.015)。结论在肝功能良好的HCC合并门静脉癌栓患者中,TACE是安全有效的。肿瘤大小、肿瘤类型、远处转移、Child-Pugh分级是影响患者生存的最主要因素,为临床医生选择合适的介入治疗患者提供了有力证据。     

Efficacy of hepatic resection vs transarterial chemoembolization for solitary huge hepatocellular carcinoma

AIM: To compare the efficacy of hepatic resection (HR) and transarterial chemoembolization (TACE) for patients with solitary huge (≥ 10 cm) hepatocellular carcinoma (HCC).METHODS: Records were retrospectively analyzed of 247 patients with solitary huge HCC, comprising 180 treated by HR and 67 by TACE. Long-term overall survival (OS) was compared between the two groups using the Kaplan-Meier method, and independent predictors of survival were identified by multivariate analysis. These analyses were performed using all patients in both groups and/or 61 pairs of propensity score-matched patients from the two groups.RESULTS: OS at 5 years was significantly higher in the HR group than the TACE group, across all patients (P = 0.002) and across propensity score-matched pairs (36.4% vs 18.2%, P = 0.039). The two groups showed similar postoperative mortality and morbidity. Multivariate analysis identified alpha-fetoprotein ≥ 400 ng/mL, presence of vascular invasion and TACE treatment as independent predictors of poor OS.CONCLUSION: Our findings suggest that HR can be safe and more effective than TACE for patients with solitary huge HCC.     

Factors linked to longterm survival of patients with hepatocellular carcinoma accompanied by tumour thrombus in the major portal vein after surgical resection

Objectives

The prognosis in patients with hepatocellular carcinoma (HCC) accompanied by main portal vein tumour thrombus (MPVTT) is poor. The aim of this study was to clarify the factors linked to survival of >5 years after hepatectomy in HCC patients with MPVTT.

Methods

Twenty-nine HCC patients with MPVTT were divided into two groups comprising, respectively, patients who survived >5 years after hepatectomy (survivors, n = 5) and those who did not (non-survivors, n = 24). The two groups were compared.

Results

Overall survival rates at 1, 3 and 5 years were 62.1%, 24.1% and 17.2%, respectively. Four (80.0%) 5-year survivors had recurrences of HCC in which the number of recurrent nodules was under four. Three (21.4%) of the 14 non-survivors who underwent curative resection experienced recurrences of HCC and all of them demonstrated fewer than four recurrent nodules (P = 0.0114). Local therapy, such as radiofrequency ablation and resection of recurrence, had more often been used in survivors than in non-survivors (P = 0.0364).

Conclusions

Although surgical outcomes in patients with HCC accompanied by MPVTT are unsatisfactory, some patients do enjoy longterm survival. When the number of recurrent nodules is less than four, local therapy should be selected with the aim of achieving 5-year survival.     

Complete response by a combination of 5-fluorouracil and interferon-alpha chemotherapy for lung metastasis of hepatocellular carcinoma after hepatic resection with portal and hepatic vein tumor thrombectomy.

A 75-year-old female was admitted to our hospital and diagnosed with hepatocellular carcinoma (HCC). Computed tomography (CT) revealed a liver tumor with tumor thrombi in the portal trunk and main hepatic vein, as well as small lung metastases. The patient had good liver function with no sign of hepatitis B or C infection. She underwent right trisectionectomy of the liver with tumor thrombectomy. Intrahepatic recurrence and progression of lung metastases were observed 4 months later. Intrahepatic recurrent tumors were treated with transcatheter arterial chemoembolization (TACE), and lung metastases were treated with systemic combination chemotherapy of 5-fluorouracil (5FU) and interferon-alpha (IFN-alpha). Computed tomography showed no viable lesions in the liver and lung 6 months after these treatments. The patient has been disease free for 18 months. Prognosis is poor for patients with hepatocellular carcinoma with portal vein tumor thrombus (PVVT) or extrahepatic metastasis. This systemic combination chemotherapy with 5-fluorouracil and interferon-alpha might be effective for patients with good liver function when intrahepatic lesions are well controlled by multidisciplinary treatments, including hepatic resection with tumor thrombectomy.