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.     

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.     

Successful preoperative treatment for hepatocellular carcinoma with tumor thrombus in the major portal branch by three-dimensional conformal radiation therapy--two case reports

The prognosis of hepatocellular carcinoma (HCC) patients with tumor thrombus in the main portal branch (PVTT) is very poor and a standard treatment regimen for HCC with PVTT has not yet been established. Therefore, a new strategy is necessary to control the patients of HCC with PVTT. Conventional radiation therapy for HCC was not effective because of low liver tolerance. On the other hand, because three-dimensional conformal radiation therapy (3D-CRT) can focus high-dose irradiation on a small area, we tried it for patients with PVTT as the preoperative adjuvant treatment. 3D-CRT which targeted the PVTT was performed for two HCC patients with PVTT before radical hepatectomy. Treatment schedules of 3D-CRT were as follows: in Case 1, the daily fraction size was 3 Gy, given five times per week, and the total dose was 39 Gy. In Case 2, the daily size was 6 Gy and the total dose was 60 Gy. Three or four weeks after 3D-CRT, the main tumor and PVTT were completely removed. On histological examination, the PVTT showed complete necrosis in Case 1, and 60% necrosis in Case 2. No serious complications occurred, and there have been no recurrences for more than one year after surgery in both cases. 3D-CRT targeting the PVTT may be promising as a preoperative adjuvant therapy for HCC with PVTT.     

肝癌伴门静脉高压症的肝切除术

目的探讨合并门脉高压症的肝癌患者手术切除疗效。方法分析东方肝胆医院1996年至2001年共626例肝癌患者的临床资料,随访终点为2008年9月1日,以死亡作为终点事件。对外科治疗的生存率及预后相关危险因素进行分析。结果合并门脉高压症患者术后1、3、5、10年生存率分别为79.9%、48.7%、37.3%和21.2%,非门脉高压症患者分别为82.7%、54.8%、42.4%和29.7%,两者差异无统计学意义(P>0.05);肿瘤数目>1个、微血管癌栓、肿瘤无包膜或不完整、肿瘤直径>10cm及HBsAg阳性是影响术后生存的独立危险因素。结论门脉高压症并不是肝癌外科手术的禁忌证,对于合并有门脉高压症的肝癌患者,只要肝功能储备良好,肝切除术仍能获得较好的术后生存率。     

Hepatectomy for hepatocellular carcinoma with portal vein tumor thrombus

Despite surgical removal of tumors with portal vein tumor thrombus(PVTT) in hepatocellular carcinoma(HCC) patients, early recurrence tends to occur, and overall survival(OS) periods remain extremely short. The role that hepatectomy may play in long-term survival for HCC with PVTT has not been established. The operative mortality of hepatectomy for HCC with PVTT has also not been reviewed. Hence, we reviewed recent literature to assess these parameters. The OS of patients who received hepatectomy in conjunction with multidisciplinary treatment tended to be superior to that of patients who did not. Multidisciplinary treatments included the following: preoperative radiotherapy on PVTT; preoperative transarterial chemoembolization(TACE); subcutaneous administration of interferon-alpha(IFN-α) and intra-arterial infusion of 5-fluorouracil(5-FU) with infusion chemotherapy in the affected hepatic artery; cisplatin, doxorubicin and 5-FU locally administered in the portal vein; and subcutaneous injection of IFN-α, adjuvant chemotherapy(5-FU + Adriamycin) administration via the portal vein with postoperative TACE, percutaneous isolated hepatic perfusion and hepatic artery infusion and/or portal vein chemotherapy. The highest reported rate of operative mortality was 9.3%. In conclusion, hepatectomy for patients affected by HCC with PVTT is safe, has low mortality and might prolong survival in conjunction with multidisciplinary treatment.     

Hepatic resection with tumor thrombectomy for hepatocellular carcinoma with tumor thrombi in the major vasculatures.

BACKGROUND/AIMS: It is still controversial whether surgical or non-surgical treatments should be adopted for hepatocellular carcinomas (HCC) with tumor thrombi (TT) in the major vasculatures. We evaluate the effectiveness of and the indications for hepatic resection with tumor thrombectomy for such patients. METHODOLOGY: Seventeen patients with TT in the major vasculatures caused by HCC were enrolled. Eleven patients had Vp3 TT, 5 patients had Vv3 TT, and 1 patient had Vp3 and Vv3 TT, concurrently. Out of the 17 patients, 13 underwent hepatic resections with tumor thrombectomies and the remaining 4 received only hepatic resections without tumor thrombectomies. RESULTS: In patients with Vp3 TT, median and mean survival times were 7.8 and 18.5 months, respectively, and 1- and 5-year survival rates were 36.4% and 18.2%, respectively. In patients with Vv3 TT, median and mean survival times were 9.9 and 8.4 months, respectively. Patients who underwent hepatic resections with tumor thrombectomies had significantly better prognoses than those who did not receive tumor thrombectomies (p=0.0039). CONCLUSIONS: The prognosis of HCC patients with TT in the major vasculatures, who have relatively small primary tumors, good hepatic functional reserves and no distant metastases should be good, if hepatic resections with tumor thrombectomies are performed.     

Surgical treatment for hepatocellular carcinoma with portal vein tumor thrombus

BACKGROUND/AIMS: To study the value of surgical treatment for hepatocellular carcinoma (HCC) with portal vein tumor thrombus (PVTT). METHODOLOGY: From January 1997 to December 2001, 63 cases of HCC with portal vein tumor thrombus underwent liver resection combined with PVTT removal (group 1). Between December 2001 and December 2003, 20 patients received adjuvant portal vein chemotherapy (PVC) after the surgical procedures mentioned above (group 2). Treatment outcome and the surgical features in these two groups were studied. RESULTS: The median overall survival in group 2 was significantly longer than that in group 1 (10.9 months vs. 7.8 months, p < 0.05). There were significant differences between the survival of the two groups (log-rank, p < 0.05). In group 1 the 1-, 3-, and 5-year survival rates were 18.0%, 14.8% and 1.6%, respectively. In group 2 the 1-year survival rate was 30%. CONCLUSIONS: Liver resection combined with PVTT removal and the postoperative PVC is beneficial to the survival of HCC patients with PVTT. Postoperative PVC might enhance the effect of these surgical approaches.     

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.     

A new classification for hepatocellular carcinoma with portal vein tumor thrombus

Background/purpose

We aimed to correlate the survival of patients with hepatocellular carcinoma (HCC) with macroscopic portal vein tumor thrombus (PVTT) who underwent partial hepatectomy with or without portal thrombectomy with our PVTT classification. Currently, different staging systems for HCC are widely used in clinical practice. However, they lack the refinement in giving prognosis and guiding surgical treatment once macroscopic PVTT is present.

Methods

A retrospective study was carried out, in a single tertiary center, from January 2001 to December 2004 on 441 patients who underwent partial hepatectomy with or without portal thrombectomy for HCC with macroscopic PVTT. Overall survival was examined to determine whether it was correlated with our PVTT classification, and with the TNM staging, Cancer of the Liver Italian Program (CLIP) scoring system, and the Japan Integrated Staging (JIS) scoring system.

Results

With our PVTT classification, the numbers (percentages) of patients with types I, II, III, and IV PVTT were 144 (32.7%), 189 (42.9%), 86 (19.5%), and 22 (5.0%), respectively. The corresponding 1-, 2-, and 3-year overall survival rates for types I to IV PVTT were 54.8, 33.9, and 26.7%; 36.4, 24.9, and 16.9%; 25.9, 12.9, and 3.7%; and 11.1, 0, and 0%, respectively (log-rank of the survival curves P?<?0.0001). Using the TNM system, the majority of patients were classified as stage III (n?=?379 or 85.9%). Similarly, the majority of patients (n?=?388 or 88.0%) were classified as having CLIP scores of 2 (n?=?143, or 32.4%), 3 (n?=?171, or 38.8%), and 4 (n?=?74, or 16.8%). The 1-, 2-, and 3-year overall survivals for these 3 CLIP scores were very similar. Using the JIS score, the majority of patients (n?=?372 or 84.4%) were classified with a JIS score of 2. The 1-, 2-, and 3-year overall survivals of patients with a JIS score of 2 were worse than those of the patients with a JIS score of 1 (this was expected) as well as being worse than those with a JIS score of 3 (this was unexpected). Thus, the latter 3 systems of classification were not refined enough, and they were inadequate for stratifying HCC with macroscopic PVTT treated with partial hepatectomy with or without thrombectomy.

Conclusions

In patients with HCC with macroscopic PVTT treated by partial hepatectomy with or without thrombectomy, our PVTT classification better stratified and predicted prognosis than the TNM staging, CLIP scoring system, and JIS scoring system, which were unrefined and inadequate for this group of patients.     

Chemotherapy for hepatocellular carcinoma with portal hypertension due to tumor thrombus

A case of hepatocellular carcinoma (HCC) complicated by tumor thrombosis of the main trunk is presented. Four courses of hepatic arterial infusion therapy, via a subcutaneously implanted injection port, were performed using cisplatin (10 mg for 1 hour on days 1-5) and 5-fluorouracil (250 mg for 5 hours on days 1-5). After four courses of the chemotherapy, marked reduction in size of HCC and the tumor markers were noted. The esophageal varices and ascites were improved after the chemotherapy with a recanalization of the left branch of the portal vein. The patient was doing well with a survival period of 28 months after the chemotherapy. These encouraging results suggested that the present therapy, based on the biochemical modulation, was a useful option for advanced HCC with portal hypertension due to tumor thrombosis of the main portal vein.     

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…     

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。     

肝细胞癌伴门静脉癌栓的手术治疗

门静脉癌栓(PVTT)是肝细胞癌(简称肝癌)重要的生物学特性,也是其严重并发症和转移方式,手术切除仍然是目前肝癌伴PVTT最有效的治疗方法。介绍了肝癌伴PVTT手术治疗的历史与现状、PVTT形成的解剖学基础、PVTT分型、手术适应证、术式选择以及手术疗效评价。认为在循证医学的基础上建立个体化多学科治疗模式,可能是肝癌伴PVTT治疗的发展方向。     

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.     

Prognostic factors for hepatocellular carcinoma presenting with macroscopic portal vein tumor thrombus

BACKGROUND/AIMS: This study examines the prognostic factors including radiological findings of hepatocellular carcinoma presenting with macroscopic portal vein tumor thrombus. METHODOLOGY: From September 1992 to December 2002, 107 patients with hepatocellular carcinoma and a macroscopic portal vein tumor thrombus were treated at the National Cancer Center Hospital East. Patients' characteristics and diagnostic findings of computed tomography, angiography and computed tomography angiography were analyzed to determine the factors significantly related to the patients' prognosis. RESULTS: Enhanced portal vein tumor thrombus, main tumor occupying over 40% of the liver and distribution of tumors significantly affected survival. Cavernous transformation, thread and streak signs, arterio-portal shunt, extent of tumor thrombus, grade of venous invasion and tumor size did not affect survival. Clinical findings showed that Child-Pugh classification score over 7, etiology of hepatitis, total bilirubin over 2.2 mg/dL, prothrombin time under 50% and liver transaminases over 100 IU/L were poor prognostic factors. Multivariate analysis showed that AST over 100 IU/L, viral hepatitis and tumor occupying over 40% of the liver strongly affected the prognosis. CONCLUSIONS: Based on the present results, the most strongly affected prognostic factor was liver function as indicated by high level of transaminases. Various radiological findings did not affect survival. The elevation of transaminases seemed due to destruction of hepatocytes by growing tumor and circulatory disruption due to portal vein tumor thrombus. We concluded that radiological findings of hepatocellular carcinoma presenting with portal vein tumor thrombus indicated only intrahepatic status but not survival. First treatment for hepatocellular carcinoma presenting with portal vein tumor thrombus should be to improve the liver function. Treatment against hepatitis virus might be important and patients with AST over 100 IU/L and a tumor occupying over 40% should not undergo surgical resection.     

Spontaneous regression of diffuse intrahepatic recurrence with portal vein tumor thrombus after resection of hepatocellular carcinoma

We report a rare case of spontaneous regression of diffuse intrahepatic recurrence with portal vein tumor thrombus (PVTT) after resection of hepatocellular carcinoma (HCC). A 68-year-old man with hepatitis C virus-related liver cirrhosis presented with a 40 mm tumor in the right anterior segment of the liver. The tumor was diagnosed as HCC by typical imaging findings and elevated serum alpha-fetoprotein (AFP) (716 ng/ml) and protein induced by vitamin K absence II (PIVKA II) (8,100 ng/ml). A right anterior sectionectomy of the liver was performed. Microscopically, the tumor was moderately differentiated HCC. Four months after resection, a computed tomography (CT) scan showed diffuse intrahepatic recurrence with PVTT. Serum AFP was 12,319 ng/ml and PIVKA II was 168,000 ng/ml. The patient did not receive any further treatment for HCC including herbal medicine, and stopped smoking. Two years and 5 months later, no lesion was detected on a CT scan when serum AFP was 1.9 ng/ml. Ischemia due to main portal vein occlusion and rapid tumor growth might have induced tumor regression in the present case. Moreover, abstention from smoking might have improved his immunological function.     

Hepatic resection for hepatocellular carcinoma based on tumor hemodynamics

Survival or disease‐free survival is not considered an appropriate surrogate outcome for the locoregional curability (i.e. surgical margin) of hepatectomy for hepatocellular carcinoma because these are greatly influenced by non‐metastatic factors like multicentric carcinogenesis (MC) or liver function. Hepatocellular carcinoma metastasizes by hematogenous seeding; therefore, the tumor blood flow (TBF) drainage area is a high‐risk area for intrahepatic metastasis, and can be identified by computed tomography under hepatic arteriography and completely resected as part of the surgical margin. The TBF pattern is classified into marginal, portal vein or hypovascular types. Partial hepatectomies were mostly performed in patients with marginal or hypovascular type, whereas anatomical surgery was frequently performed in those with portal vein type. Pathologically, nodules inside the TBF drainage area were moderately or poorly differentiated carcinomas, suggesting intrahepatic metastasis. In contrast, those outside the drainage area were frequently solitary and contained well‐differentiated carcinoma, which is consistent with MC. The pattern of tumor recurrences after TBF‐based hepatectomy is divided into two distinct groups – “a few nodules” and “many nodules in multiple segments or extrahepatic” – indicating that intrahepatic recurrences develop from MC and from circulating tumor cells in peripheral blood, respectively. Anatomical resection has not shown a survival benefit over that of TBF‐based partial hepatectomy. TBF‐based hepatectomy enables us to preserve liver function without compromising locoregional curability.