Role of transarterial chemoembolization for hepatocellular carcinoma before liver transplantation with special consideration of tumor necrosis

Abstract:  Several authors suggest that local ablative therapies, specifically transarterial chemoembolization (TACE), may control tumor progression of hepatocellular carcinoma (HCC) in patients who are on the waiting list for liver transplantation (orthotopic liver transplantation, OLT). There is still no evidence if TACE followed by OLT is able to prevent recurrence of tumor, to prolong survival rate of the patients on the waiting list, or to improve the survival after OLT. We report 27 patients with HCC who underwent OLT. From these patients, 15 were pre-treated with TACE alone or in combination with percutaneous ethanol injection (PEI) or laser-induced thermo therapy (LITT). Mean time on the waiting list was 214 d for treated patients and 133 d for untreated patients. Comparing pre-operative imaging and histopathological staging post-transplant, we found 13 patients with tumor progression out of which five were treated with TACE. In two of the TACE patients a decrease of lesions could be achieved. In a single patient, there was no evidence of any residual tumor. Only one patient displayed tumor progression prior to OLT despite undergoing TACE. Comparison of outcome in patients undergoing TACE or having no TACE was not statisitically significant (p = 0.5). In addition, our analysis showed that progression either in the total study population or in the TACE group alone is associated with a significant poorer outcome concerning overall survival (p = 0.02 and p = 0.02).     

Comparison of two techniques of transarterial chemoembolization before liver transplantation for hepatocellular carcinoma: a case-control study.

Supraselective transarterial chemoembolization (STACE) more efficiently targets chemotherapy delivered via the feeding arterial branches of the tumor than does conventional transarterial chemoembolization (TACE). However, the hypothesis of its greater efficacy compared with the latter is subject to controversy. The aim of the present study was to compare STACE to conventional TACE in a controlled study of candidates for liver transplantation (LT) for hepatocellular carcinoma (HCC). Patients were matched for factors associated with HCC recurrence and survival. Sixty patients were included: 30 who were treated with STACE and 30 treated with conventional TACE. The 2 groups were similar in terms of matched criteria. In the overall population (uni- and multinodular HCC), there was no marked difference between the 2 groups in 5-year disease-free survival: 76.8% vs. 74.8%. In sensitivity analysis of patients considered to be the best candidates for TACE (uninodular HCC < or =5 cm), there was a trend toward significance between STACE and TACE in 5-year disease-free survival: 87% vs. 64% (P = 0.09). The only factor associated with complete tumor necrosis was STACE in the overall population (30.8% vs. 6.9%, P = 0.02), with a similar trend in the subgroup of patients with a single nodule (33.3% vs. 6.7%, P = 0.06), whereas the mean number of procedures was similar in the 2 groups (mean, 1.3 procedures; range 1-5 procedures; P = NS). STACE is more efficient at inducing complete tumor necrosis in the liver. This study observed trends toward improvement in the disease-free survival of patients with uninodular HCC < or =5 cm. Future studies focusing on such patients are warranted.     

Transarterial chemoembolization before liver transplantation in 60 patients with hepatocellular carcinoma

Tumor recurrence is a major problem after orthotopic liver transplantation (OLT) in patients with hepatocellular carcinoma (HCC). In 60 patients OLT was performed for HCC after pretreatment by repeated transarterial chemoembolization (TACE). Forty-four recipients exceeded the Milan criteria. Recurrence-free 5-year survival was 65.2% and 5-year freedom from recurrence was 73.2%. During the waiting time, 14 patients experienced minimal change, which did not fulfill the definition of tumor progression according to official oncological criteria. Five-year freedom from recurrence among patients with stable compared with progressive disease was 93.3% versus 28.1%, respectively (P = .0001). A strict TACE pretreatment protocol may select patients with obviously biologically less aggressive tumors, who are suitable for OLT even if the HCC exceeds the commonly accepted listing criteria.     

Response to transarterial chemoembolization as a biological selection criterion for liver transplantation in hepatocellular carcinoma.

Criteria to select patients with hepatocellular carcinoma (HCC) for liver transplantation (LT) are based on tumor size and number of nodules rather than on tumor biology. The present study was undertaken to assess the role of transarterial chemoembolization (TACE) in selecting patients with tumors suitable for LT. Ninety-six consecutive patients with HCC were treated by repeatedly performed TACE, 62 of them exceeding the Milan criteria. Patients meeting the Milan criteria were immediately listed, and patients beyond the listing criteria were listed upon downstaging of the tumor following successful TACE. Fifty patients were finally transplanted. Of these 50 patients, 34 exceeded the Milan criteria. In these 96 patients, overall 5-year survival was 51.9%. However, it was 80.9% for patients undergoing LT and 0% for patients without transplantation (P < 0.0001). Tumor recurrence was primarily influenced by the control of the disease through continued TACE during the waiting time. Freedom from recurrence after 5 years was 94.5% in patients (n = 39) with progress-free TACE during the waiting time. Tumor recurrence was significantly higher in patients (n = 11) who after initial response to TACE progressed again before LT (freedom from recurrence 35.4%; P = 0.0017). Progress-free course of TACE during the waiting time (P = 0.006; risk ratio, 8.95), and a limited number of tumor nodules as assessed in the surgical specimen (P = 0.025; risk ratio, 0.116) proved to be significant predictors for freedom from recurrence in the multivariate analysis. Milan criteria were without impact on recurrence. Our data suggest that sustained response to TACE is a better selection criterion for LT than the initial assessment of tumor size or number.     

Impact of neoadjuvant transarterial chemoembolization on tumor recurrence and patient survival after liver transplantation for hepatocellular carcinoma: a retrospective analysis

Transarterial chemoembolization (TACE) has gained wide acceptance as a bridge to liver transplantation (LT) in patients with hepatocellular carcinoma (HCC). Aim of this analysis was to compare long‐term results with and without neoadjuvant TACE and to identify subgroups, which particularly benefit from TACE. Patients with HCC transplanted at our center were retrospectively analyzed. The following were excluded to increase consistency: incidental‐HCC, Child‐C, living‐related‐LT, other HCC‐specific‐treatment. Of 336 patients, 177 were subject of this analysis, 71 received TACE and 106 no HCC therapy. Patients with and without TACE showed similar five‐yr survival (73/67%) and recurrence rates (23/29%). Progression on the waiting list was associated with a higher recurrence rate in the TACE (50 vs.12%) and the non‐TACE group (40 vs. 22%). HCC recurrence was reduced in patients inside Milan (0.053) and UCSF (0.037) criteria by neoadjuvant TACE but not outside UCSF (0.99). Also a trend towards an improved survival was seen within these criteria. Our large single center experience suggests that TACE lowers the HCC recurrence rate in patients inside the Milan and UCSF criteria. Moreover, the response to TACE is a good indicator of low recurrence rates. The effect of TACE might be more pronounced in patients with longer waiting time than in this cohort (mean, 4.6 months).     

Impact of pretransplantation transarterial chemoembolization on survival and recurrence after liver transplantation for hepatocellular carcinoma.

The actual impact of transarterial chemoembolization before liver transplantation (LT) for hepatocellular carcinoma (HCC) on patient survival and HCC recurrence is not known. Between 1985 and 1998, 479 patients with HCC in 14 French centers were evaluated for LT. Among these 479 patients, this case-control study included 100 patients who received transarterial chemoembolization before LT (TACE group) and 100 control patients who did not receive chemoembolization (no-TACE group). Patients and controls were matched for the pre-LT tumor characteristics, the period of transplantation, the time spent on the waiting list, and pre- and posttransplantation treatments. Kaplan-Meier estimates were calculated 5 years after LT and were compared with the log-rank test. The mean waiting time before LT was 4.2 +/- 3.2 months in the TACE group and 4.3 +/- 4.4 months in the no-TACE group. The median number of TACE procedures was 1 (range: 1-12). Demographic data, median alpha-fetoprotein level (21.6 ng/mL and 22.0 ng/mL, respectively), and pre- and post-LT morphologic characteristics of the tumors did not differ in the TACE and no-TACE groups. Overall 5-year survival was 59.4% with TACE and 59.3% without TACE (ns). Survival rates did not differ significantly between the two groups with respect to the time on the waiting list, the tumor diameter, or the type of TACE (selective or nonselective). In the TACE group, 30 patients had tumor necrosis > or =80% on the liver explant with a 5-year survival rate of 63.2%, compared with 54.2% among their matched controls (P = 0.9). In conclusion, with a mean waiting period of 4.2 months and 1 TACE procedure, pre-LT TACE does not influence post-LT overall survival and disease-free survival.     

肝癌肝移植前经肝动脉化学药物栓塞的临床研究

肝移植作为对某些肝癌病人的一种有效的治疗手段日益受到重视[1].但由于肝移植病人的逐渐增加和肝脏供体的短缺,使术前等待时间越来越长,导致很多病人在等待移植期间因病情恶化而失去了肝移植机会.     

肝细胞癌肝移植前介入性干预的研究现状

肝移植是肝细胞癌(HCC)患者最有希望的治疗选择之一。探讨影响HCC肝移植术后生存、预后的问题及对策是现阶段的重要课题。国内外均在尝试用多种围移植术期辅助治疗来降低术后复发和提高生存率，其中以介入性干预方法使用最多，且疗效引人注目。     

Does neoadjuvant chemoradiation downstage esophageal carcinoma?

BACKGROUND: Neoadjuvant chemoradiotherapy is administered to patients with esophageal carcinoma with the belief that this will both downstage the tumor and improve survival. Endoscopic ultrasound (EUS) is currently the most accurate method of staging esophageal cancer for tumor (T) and lymph node (N) status. Because both EUS and neoadjuvant therapy for esophageal carcinoma are relatively new, there are few data examining the relationship between EUS stage and histological stage (the stage after resection) in patients receiving neoadjuvant therapy. METHODS: To determine the effect of neoadjuvant chemoradiotherapy on T and N stage as determined by EUS, we retrospectively compared two groups of patients with esophageal cancer staged by EUS. One group (33 patients) underwent neoadjuvant therapy (Walsh protocol: 5-fluorouracil, cisplatin, and 4000 rads of external beam radiation) followed by resection. The second group (22 patients), a control group, underwent resection without neoadjuvant therapy. We then compared histological stage to determine if there was a downstaging in the patients receiving neoadjuvant therapy. Survival was evaluated as well. RESULTS: EUS accurately predicted histologic stage. In the control group EUS overestimated T stage in 3 of 22 (13%), underestimated N stage in 2 of 22 (9%), and overestimated N stage in 2 of 22 (9%) of patients. Preoperative radiochemotherapy downstaged (preoperative EUS stage versus pathologic specimen) 12 of 33 (36%) of patients whereas only 1 of 22 (5%) of patients in the control group was downstaged. Complete response (no tumor found in the surgical specimen) was observed in 5 of 33 (15%) of patients receiving radiochemotherapy. Survival was prolonged significantly in patients receiving radiochemotherapy: 20.6 months versus 9.6 months for those (stage II or III) patients not receiving radiochemotherapy (P <0.01). Operative time, operative blood loss, and length of stay were not significantly different between groups. Perioperative mortality was higher in the radiochemotherapy group (13%) compared with the no radiochemotherapy group (5%) but did not achieve statistical significance. CONCLUSIONS: EUS accurately stages esophageal carcinoma. Neoadjuvant radiochemotherapy downstages esophageal carcinoma for T and N status. In our nonrandomized study, neoadjuvant therapy conferred a significant survival advantage. Operative risk appears to be increased in patients receiving neoadjuvant radiochemotherapy prior to esophagectomy.     

Value of 18-FDG-positron emission tomography/computed tomography before and after transarterial chemoembolization in patients with hepatocellular carcinoma undergoing liver transplantation: initial results

Introduction

Liver transplantation is the treatment of choice for various types of end-stage liver disease and the most appropriate alternative for the treatment of hepatocellular carcinoma (HCC)-associated liver cirrhosis. The aim of this study was to describe our initial experience with the use of 18-FDG positron emission tomography (PET)/computed tomography CT before and after transarterial chemoembolization (TACE) in HCC patients undergoing liver transplantation, seeking to predict the percentage of tumor necrosis achieved by TACE procedures.

Patients and Methods

From January 2007 through December 2009, 39 patients with HCC and liver cirrhosis were included in our liver transplantation program. We selected the 6 subjects who underwent 18-fluorodeoxyglucose PET/CT (18-FDG PET/CT) pre- and post-TACE.

Results

The median SUV (standarized uptake value) in the lesions studied were 4 (range, 2.79-6.95) before TACE with a median post-TACE SUV of 0 (range, 0-4). Among patients whose post-TACE SUV decreased to <3, the percentage of necrosis after studying the hepatectomy was >80%.

Conclusion

Performance of an 18-FDG PET/CT before and after TACE and comparison of SUV in patients with HCC awaiting liver transplantation provided valuable information regarding the effectiveness of TACE.     

超“UCSF标准”肝细胞癌肝移植术前经肝动脉化疗栓塞的疗效

目的: 评估经肝动脉化疗栓塞（TACE）在超“UCSF标准”肝细胞癌（HCC）肝移植术前治疗的安全性及疗效。方法: 回顾性分析2003年1月至2013年3月在本院行肝移植治疗的83例超“UCSF标准”的成年HCC病人临床资料,根据术前是否采取TACE治疗分为TACE治疗组（63例）与对照组（20例）。比较两组病人术后急性排异、胆道并发症和血管并发症发生率、无瘤生存率及总生存率。结果: TACE治疗组在肝移植术前平均进行了（2.0±1.3）次TACE疗程,末次治疗至肝移植的平均时间为（15.7±8.4） d。TACE治疗组与对照组相比,在肝移植术后急性排异、肝动脉栓塞和胆道并发症发生率差异无统计学意义（P>0.05）。TACE治疗组无瘤生存率及总生存率明显优于对照组（P<0.05）。分层分析表明,TACE治疗后获得完全反应或部分反应的HCC病人行肝移植1、3、5年无瘤生存率及总生存率明显高于TACE治疗后无反应组（P<0.05）。TACE治疗后肿瘤降期至“UCSF标准”的HCC病人行肝移植1、3、5年无瘤生存率及总生存率明显高于降期治疗后未达到“UCSF标准”的病人（P<0.05）。结论: 肝移植术前TACE治疗可延长病人无瘤生存及总生存时间。肝移植术前TACE降期治疗安全,仅1例发生肝动脉栓塞并发症。     

The significance of transarterial embolization for advanced hepatocellular carcinoma in liver transplantation

INTRODUCTION: Transarterial embolization (TAE) is the treatment of choice for advanced HCC to control or even induce tumor shrinkage. The aim of this study was to evaluate the effect of pretransplantation TAE for treatment of advanced HCC. MATERIAL AND METHODS: From 1996 to 2002, we studied 12 cirrhotic patients with HCC, including six who met and six who exceeded the Milan criteria. All patients had sufficient hepatic function to undergo TAE. Liver transplantations were performed subsequently and they were followed prospectively for a median of 22 months (range = 12 to 53 months). RESULTS: The explanted livers from the 12 patients who had undergone TAE were noted to have extensive tumor necrosis. The pathological specimens at LT showed downstaging of the HCC, which allowed those six patients to meet the Milan criteria. The overall 1- and 2-year survival rates were 92% and 73%, respectively. The overall 1- and 2-year disease-free survival rates were 92% and 73%, respectively. One death unrelated to liver disease at 2 years after LT was noted in the downgraded group. One patient of the initially eligible group developed lung metastasis at 6 months and died at 12 months after LT. CONCLUSION: TAE is effective to downstage advanced HCC and reduce the dropout rate on the LT waiting list. Pre-LT TAE may be considered as a better therapeutic strategy for patients with advanced HCC.     

C臂CT扫描用于TACE治疗肝细胞癌

目的探索C臂CT(CCT)扫描在TACE治疗肝细胞癌中的价值。方法对80例接受TACE治疗的肝细胞癌患者行CCT扫描。观察患者CCT图像检出肝内病灶的情况,并与DSA及治疗前其他影像学检查的检出情况进行比较;观察CCT图像对病灶异常供血动脉的显示情况,评价其对于TACE操作的指导作用。结果 80例患者中,CCT扫描检出病灶139个,其中4例患者较64排螺旋CT扫描共多检出5个病灶,2例患者较常规DSA检查共多检出2个病灶。TACE治疗前,77例患者CCT扫描显示131个病灶供血动脉清晰满意,其中28例(28/77,36.36%)为微导管超选择插管治疗提供了直接的帮助;发现4例患者肝癌病灶异常供血动脉,1例病灶供血动脉走行异常显示清楚。结论在应用TACE治疗肝细胞癌过程中,CCT扫描有助于检出肝内病灶、显示病灶供血动脉和动脉异常走行,对TACE操作具有非常重要的价值。     

Re-evaluation of lipiodolized transarterial chemoembolization therapy for intrahepatic recurrence of hepatocellular carcinoma after curative liver resection

Background/Purpose  While lipiodolized transarterial chemoembolization (lip-TACE) is effective for treating unresectable hepatocellular carcinoma (HCC), its effect for treating recurrent HCC after curative liver resection needs to be clarified. Methods  Of 163 patients who had undergone curative liver resection between 1992 and December 2003, 65 patients (39.8%) had recurrent HCC in the liver without extrahepatic recurrence and were indicated for lip-TACE. The overall survival rate after lip-TACE was calculated, and its correlation with factors such as the histology of the primary HCC and background noncancerous tissue were analyzed. Results  The overall survival rates after lip-TACE after the detection of the first recurrent HCC were 82.6%, 44.5%, and 24.8% at 1, 3, and 5 years, respectively. The factors affecting patient survival after lip-TACE were microscopic portal venous involvement of HCC at liver resection, grade of inflammation in the noncancerous liver parenchyma, and recurrence within 1 year after the initial liver resection. Multivariate analysis showed that the period between the resection and first recurrence had the highest hazard ratio. Conclusions  Lip-TACE is a reasonable procedure for treating recurrent HCC in selected patients who are not eligible for hepatic re-resection. When HCC recurred within 1 year from the primary liver resection, the effect of lip-TACE on patient survival was limited.     

Adjuvant transarterial chemoembolization for patients with hepatocellular carcinoma involving microvascular invasion

Background

Microvascular invasion (MVI) has recently been reported to be an independent prognostic factor in patients with hepatocellular carcinoma (HCC). This study compared the outcomes of adjuvant transarterial chemoembolization (A-TACE) after hepatic resection (HR) in patients with HCC involving MVI.