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.     

Application of cystoscope in surgical treatment of hepatocellular carcinoma with portal vein tumor thrombus

Development of portal vein tumor thrombus deteriorates the prognosis of hepatocellular carcinoma, while surgical treatment can offer a promising prognosis for selected patients. However, the possibility of residual lesions in portal vein after conventional thrombectomy is a main risk factor leading to postoperative recurrence. Therefore, ensuring the complete removal of tumor thrombus during operation is critical to improve prognosis. For the first time, we report here one case of hepatocellular carcinoma with portal vein tumor thrombus in which cystoscope was successfully applied as a substitute of intravascular endoscope to visualize the cavity of the portal vein. The patient was a 61-year-old man with a 7-cm tumor in the right lobe of the liver, with tumor thrombus invading the right branch and adjacent to the conjunction of the portal vein. After removal of the tumor, the Olympus CYF-VA2 cystoscope was used to check the portal vein from the opening stump of the right branch of the portal vein. In this case, residual thrombus tissue was found near the opening stump and the conjunction of the portal vein. The residual lesion was carefully retrieved from the stump after retraction of the cystoscope. The procedure was repeated until no residual lesion was found. The whole duration time of thrombectomy was 22.5(15 + 7.5) min. The patient was free from recurrence at 8 months after the procedure. Our work indicated that the cystoscope is a suitable substitute, with a proper size and function to check the portal vein system and ensure the curability of thrombectomy. Although welldesigned clinic trails are still needed, this procedure may further improve the postoperative prognosis of hepatocellular carcinoma with portal vein tumor thrombus.     

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.     

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。     

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.     

肝细胞癌合并门静脉癌栓治疗新进展

门静脉癌栓是肝细胞癌晚期患者常见表现之一,是导致严重并发症的决定性因素,预后极差。随着分子生物学及影像学技术的发展,外科手术切除、介入栓塞化疗、放射治疗、各种消融治疗、分子靶向治疗等手段,无论单一应用还是综合治疗均取得了丰硕成果,但目前仍缺乏合理有效的治疗规范。对近些年来关于肝细胞癌合并门静脉癌栓的治疗新进展做出总结,希望能为今后治疗方案的规范化提供参考。     

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.     

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.     

肝细胞癌合并门脉癌栓的形成分型与手术治疗进展

门静脉癌栓是肝细胞癌常见而重要的生物学特性,是影响肝细胞癌预后的最重要因素.本文就肝细胞癌合并癌栓的形成、分型与手术治疗进展作一综述.     

原发性肝癌伴门脉癌栓综合诊治的研究进展

原发性肝细胞癌（HCC）是较常见的消化道恶性肿瘤之一，其死亡率居我国恶性肿瘤的第二位，而伴有门脉癌栓（PVTT）的肝癌因易发生肝内及远处转移，被认为是预后差的主要指标之一，生存期为2．4～2．7个月。虽然HCC合并门脉癌栓是预后不良的标志，但在肝功能及一般情况允许的情况下，仍可尝试多种治疗方法以提高此类患者的生存率，综合治疗在该病的治疗中起着重要的作用。     

Spontaneous complete regression of hepatocellular carcinoma with portal vein tumor thrombus

We report herein a case of spontaneous complete regression of hepatocellular carcinoma with portal vein tumor thrombus. A 69-year-old Japanese man with chronic hepatitis C was admitted to our hospital, because of a large mass in the right hepatic lobe. He was diagnosed with hepatocellular carcinoma based on computed tomography and the elevated serum levels of alpha-fetoprotein. Abdominal angiography revealed portal vein tumor thrombus. Approximately 2 months after the initial diagnosis, alpha-fetoprotein had decreased to a normal range. Under a diagnosis of hepatocellular carcinoma, a right hepatic lobectomy was performed, and histological examination of the resected specimen revealed no viable tumor cells. The patient is alive 1 year after the surgery without evidence of recurrence.     

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 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…     

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.     

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.     

门静脉支架联合动脉化学栓塞疗法治疗肝癌合并门静脉主干癌栓

肝癌(HCC)伴有门静脉主干癌栓(MPVTT)预后极差.由被阻塞门静脉供血的正常肝组织缺血,从而损害肝功能并限制了经肝动脉化疗栓塞(TACE)在治疗HCC中的应用.经皮穿刺肝脏门静脉支架植入(PTPVS)可姑息性解除门静脉阻塞.     

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