Clinical outcome of esophageal varices after hepatic arterial infusion chemotherapy for advanced hepatocellular carcinoma with major portal vein tumor thrombus

Aim: To analyze the clinical outcome of esophageal varices (EV) after hepatic arterial infusion chemotherapy (HAIC) in patients with advanced hepatocellular carcinoma (HCC) and major portal vein tumor thrombus (Vp3/4). Methods: The study subjects were 45 consecutive patients who received HAIC for HCC with Vp3/4 between January 2005 and December 2009. HAIC comprised the combination therapy of intra‐arterial 5‐FU with interferon‐α (5‐FU/IFN) in 23 patients and low‐dose cisplatin plus 5‐FU (FP) in 22. Radiotherapy (RT) was also provided in 19 patients for portal vein tumor thrombosis. Aggravation rate for EV and overall survival rate were analyzed. Results: The aggravation rates for EV were 47% and 64% at 12 and 24 months, respectively. The survival rates were 47% and 33% at 12 and 24 months, respectively. The response rates to 5‐FU/IFN and FP were 35% and 41%, while the disease control rates in these two groups were 57% and 50%, respectively. There were no significant differences in the objective response and disease control between 5‐FU/IFN and FP. Multivariate analysis identified size of EV (F2/F3) (HR = 7.554, P = 0.006) and HCC disease control (HR = 5.948, P = 0.015) as significant and independent determinants of aggravation of EV, and HCC disease control (HR = 12.233, P < 0.001), metastasis from HCC (HR = 11.469, P = 0.001), ascites (HR = 8.825, P = 0.003) and low serum albumin (HR = 4.953, P = 0.026) as determinants of overall survival. RT for portal vein tumor thrombosis tended to reduce the aggravation rate for EV in patients with these risk factors. Conclusions: Hepatocellular carcinoma disease control was the most significant and independent factor for aggravation of EV and overall survival in HCC patients with major portal vein tumor thrombosis treated with HAIC.     

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。     

Hepatic arterial infusion chemotherapy in hepatocellular carcinoma with portal vein tumor thrombosis

AIM: To evaluate the prognostic factors and efficacy of hepatic arterial infusion chemotherapy in hepatocellular carcinoma with portal vein tumor thrombosis. METHODS: Fifty hepatocellular carcinoma (HCC) patients with portal vein tumor thrombosis (PVTT) were treated using hepatic arterial infusion chemotherapy (HAIC) via a subcutaneously implanted port. The epirubicin-cisplatin-5-fluorouracil (ECF) chemotherapeutic regimen consisted of 35 mg/m 2 epirubicin on day 1, 60 mg/m 2 cisplatin for 2 h on day 2, and 500 mg/m 2 5-fluorouracil for 5 h on days 1-3. The treatments were repeated every 3 or 4 wk. RESULTS: Three (6%) of the 50 patients achieved a complete response (CR), 13 (26%) showed partial responses (PR), and 22 (44%) had stable disease (SD).The median survival and time to progression were 7 and 2 mo, respectively. After 2 cycles of HAIC, CR was achieved in 1 patient (2%), PR in 10 patients (20%) and SD in 26 patients (52%). Significant pre-treatment prognostic factors were a tumor volume of < 400 cm 3 (P = 0.01) and normal levels of protein induced by vitamin K absence or antagonist (PIVKA)-Ⅱ (P = 0.022). After 2 cycles of treatment, disease control (CR + PR + SD) (P = 0.001), PVTT response (P = 0.003) and α-fetoprotein reduction of over 50% (P = 0.02) were independent factors for survival. Objective response (CR + PR), disease control, PVTT response, and combination therapy during the HAIC were also significant prognostic factors. Adverse events were tolerable and successfully managed. CONCLUSION: HAIC may be an effective treatment modality for advanced HCC with PVTT in patients with tumors < 400 cm 3 and good prognostic factors.     

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.     

Right hepatic lobectomy with removal of tumor thrombus from the portal vein for hepatocellular carcinoma

Hepatocellular carcinoma with tumor thrombus in the portal trunk and collateral veins in the hepatoduodenal ligament is usually considered to be unresectable. To resect the tumor, it is necessary to handle the portal trunk and bile duct after the hepatic artery and liver parenchyma have been transected without dissection of the hepatoduodenal ligament. In this way, we were able to perform right lobectomy with removal of the tumor thrombus in the portal trunk, avoiding profuse bleeding due to transection of the collateral veins. Our procedure is associated with certain problems, one being whether the tumor thrombus can be separated from the endothelium of the portal vein, and another being related to the radical extent of this operation. The major issue is the radical nature of this procedure. It is presumed that the collateral veins can be extirpated to achieve a curative operation.     

Adjuvant arterial infusion chemotherapy after resection of hepatocellular carcinoma with portal thrombosis: a pilot study

Background/Purpose

The prognosis of hepatocellular carcinoma (HCC) with tumor thrombosis of the main trunk or major branches of the portal vein (mPVTT) is extremely poor, even if it is curatively resected. Uncontrollable multiple metastases to the residual liver are often observed within several months after the operation. We report here the results of a pilot study, showing the efficacy of adjuvant arterial infusion chemotherapy after the resection of HCC with mPVTT.

Methods

Twelve patients had curative resection of HCC with mPVTT. Six of the patients were treated by the arterial infusion of a chemotherapeutic agent via a subcutaneously implanted injection port after curative resection of HCC with mPVTT. The initial course consisted of the daily administration of cisplatin (CDDP) and continuous infusion of 5-fluorouracil (5-FU). This was followed by the weekly or biweekly administration of CDDP and subsequent infusion of 5-FU until the cumulative dose of 5-FU reached 15?g.

Results

The median overall survival time was 58.0 months with adjuvant chemotherapy and 8.0 months without adjuvant chemotherapy. The median disease-free interval was 15.0 months with adjuvant chemotherapy and 4.0 months without adjuvant chemotherapy. Adverse reactions were tolerable nausea and loss of appetite.

Conclusions

This chemotherapeutic regimen achieved favorable results and may be useful as adjuvant chemotherapy in treating patients after curative resection of HCC with mPVTT.     

Subtotal hepatectomy following neoadjuvant chemotherapy for a previously unresectable hepatocellular carcinoma

An awareness of variant hepatic vascular anatomy provides vital information in the preoperative evaluation of patients with hepatocellular carcinoma. The authors present a patient with unresectable hepatocellular carcinoma who responded to combination systemic and regional chemotherapy. Because of the presence of an enlarged inferior right hepatic vein, the patient subsequently underwent successful subtotal hepatectomy with resection of all three main hepatic veins. This case illustrates that the combination of innovative neoadjuvant chemotherapy and well-planned surgical approaches may benefit a small number of patients previously deemed unresectable.     

原发性肝细胞癌伴门静脉癌栓患者接受立体定向放射治疗的疗效观察

目的评价原发性肝细胞癌伴门静脉癌栓患者接受立体定向放射治疗(射波刀)的疗效。方法收集我院2011年1月—2015年5月原发性肝细胞癌伴门静脉癌栓患者59例,均接受射波刀治疗。门静脉癌栓的大体肿瘤体积为24.6~1265.0 cm3,中位数399.0 cm3,单次分割剂量5~13 Gy/次(中位数10 Gy),照射次数4~8次(中位数6次),肿瘤剂量35~56 Gy(中位数49 Gy),每d或隔1~2 d照射1次。采用寿命表法进行生存分析,Cox回归模型分析生存相关的影响因素。结果 59例肝癌伴门静脉癌栓患者接受射波刀治疗,中位无疾病进展生存期为5.19个月,中位总生存期为11.84个月,疾病控制率为62.71%(37/59),治疗后1年、2年、3年的累积生存率分别为49.15%(29/59)、20.34%(12/59)、11.86%(7/59)。Cox回归分析显示:术前AFP水平、性别、年龄、病灶大小、肿瘤数目、肝功能Child-Pugh分级、腹水、癌栓类型及总剂量大小对患者生存期无明显影响。结论射波刀是肝癌伴门静脉癌栓患者较理想的治疗方法,可显著延长患者生存期。     

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.     

Treatment of portal vein tumor thrombus of hepatocellular carcinoma with percutaneous laser ablation

Backgrounds  Portal vein tumor thrombus (PVTT) is a common complication of hepatocellular carcinoma (HCC), and is associated with extremely poor prognosis. Patients and methods  In this retrospective study, we first evaluate the application of percutaneous laser ablation as a treatment for PVTT due to advanced hepatocellular carcinoma. 108 patients (2002.7–2005.12) that have adequate liver function and be in reasonably good general condition were enrolled at Eastern hepatobiliary surgery hospital. The thrombus was ablated via an optic fiber placed in the guide needle with the guiding of ultrasound. In the follow-ups, the serial imaging and laboratory routines were examined and the overall clinical progress was measured at regular intervals until time of death. In the clinical assessment, survival time and factors affecting survival time were analyzed. The changes of laboratory test (alanine transaminase and alpha fetoprotein) and clinical manifestation (ascites and diarrhea) of the PVTT patients before and after laser ablation were observed. Results  Patency of the tumor-occluded portal vein branch is the only factor that affect the survival time, the longer the patency time, the longer the survival time. The long-term survivals of patients in our study are 55.56, 33.58 and 22.38% at 1, 2 and 3 years, respectively. Both laboratory test and clinical presentations were improved. Αlpha fetoprotein in the positive patients decreased and alanine transaminase in the abnormal patients normalized at 1 month after the treatment. Ascites disappeared in 44.00% patients (11/25), and diarrhea ameliorated in 57.14% (12/21). Conclusion  Laser ablation might be a novel and effective treatment for PVTT associated with advanced HCC     

Survival benefits of intra-arterial infusion chemotherapy in patients with advanced hepatocellular carcinoma with portal vein tumor thrombosis.

PURPOSE:: Advanced hepatocellular carcinoma (HCC) with portal vein thrombosis has a poor prognosis. This study was undertaken to evaluate the therapeutic effects of intra-arterial infusion chemotherapy in advanced HCC, and tried to identify prognostic factors that could affect survival. METHODS AND MATERIALS:: Between January 1995 and January 2001, a total of 102 patients with advanced HCC with portal vein thrombosis were enrolled and divided into three groups: group 1 (n=24) was managed with only supportive care, group 2 (n=25) received systemic combination chemotherapy and group 3 (n=52) received intra-arterial infusion chemotherapy with 5-fluorouracil+cisplatin via implanted chemoport. RESULTS:: One-year survival rates were 0, 4, 21% and median survivals were 2, 4, 6 months in groups 1, 2, 3, respectively (p=0.003). When we divide group 3 patients into long-term (more than 8 months) or short-term survivors, long-term survivor had significantly low level of serum AST (p=0.032) and alkaline phosphatase (p=0.033). Especially, all female patients (n=9) survived more than 8 months (p=0.000). Other favorable prognostic factors for survival were cirrhosis of Child-Pugh class A (p=0.003), only one major branch involvement of the portal vein by tumor (p=0.005), presence of enhancement of tumor portion in arterial phase of CT scan (p=0.044), presence of enhancement of non-tumor portion in portal phase of CT scan (p=0.029). CONCLUSIONS:: Intra-arterial infusion chemotherapy achieved favorable results in advanced HCC with portal vein thrombosis and showed better survival in selected patients.     

Better surgical treatment method for hepatocellular carcinoma with portal vein tumor thrombus

Hepatocellular carcinoma(HCC) with portal vein tumor thrombus(PVTT) is a disease that is not uncommon, but the treatments vary drastically between Eastern and Western countries. In Europe and America, the first line of treatment is systemic therapy such as sorafenib and the surgical treatment is not a recommend option. While an increasing number of studies from China and Japan have suggested that surgical treatment results in better outcomes when compared to transcatheter arterial chemoembolization(TACE), sorafenib, or other nonsurgical treatments, and two classification systems, Japanese Vp classification and Chinese Cheng's classification, were very useful to guide the surgical treatment. We have also found that surgical treatment may be more effective, as we have performed surgical treatment for HCC-PVTT patients over a period of approximately 15 years and achieved good results with the longest surviving time being 13 years and onward. In this study, we review the efficacy and principles of current surgical treatments and introduce our new, more effective surgical technique named "thrombectomy first", which means the tumor thrombus in the main portal vein, the bifurcation or the contralateral portal vein should be removed prior to liver resection. Thus, compression and crushing of PVTT during the operation could be avoided and new intrahepatic metastases caused by tumor thrombus to the remnant liver minimized. The new technique is even beneficial to the prognosis of Cheng's classification Types Ⅲ and Ⅳ PVTT. The vital tips and tricks for the surgical approach are described.     

Treatment of hepatocellular carcinoma accompanied by portal vein tumor thrombus

INTRODUCTIONRecent progress in imaging techniques has permitted the diagnosis of hepatocellular carcinoma (HCC) at an early stage. However, portal venous invasion is still found in 12.5%-39.7% of patients with HCC[1-5]. According to the 16th National Surv…     

Hepatocellular carcinoma with portal vein tumor thrombosis: Improved treatment outcomes with external beam radiation therapy

The treatment of advanced hepatocellular carcinoma (HCC) associated with portal vein tumor thrombosis (PVTT) is very challenging because of HCC's grave prognosis. Despite many efforts to improve the treatment results, patient survival has been limited to several months. In this situation, radiotherapy has been considered as an alternative treatment modality because of the growth of knowledge about the radiotolerance of normal tissue and the advances of radiotherapy techniques such as three dimensional conformal radiotherapy, intensity modulated radiotherapy, stereotactic body radiotherapy and proton therapy. More restoration of the liver function and longer survival of the patients can be achieved by the better response after radiotherapy. However, considering the high risk of intrahepatic advanced tumor or extrahepatic dissemination by PVTT at disease presentation, a combination of radiation therapy and systemic agents will be desirable. Therefore, performing prospective randomized clinical trials is important to assess the benefits of radiotherapy and to develop combination treatment strategies.