Predictors of survival after liver transplantation for hepatocellular carcinoma associated with Hepatitis C.

The efficacy of orthotopic liver transplantation (OLT) for hepatocellular carcinoma (HCC) associated with hepatitis C virus (HCV) is not well defined. This study examines the variables that may determine the outcome of OLT for HCC in HCV patients. From 1990 to 1999, 463 OLTs were performed for HCV cirrhosis. Of these patients, 67 with concurrent HCC were included in the study. Univariate and multivariate analyses considered the following variables: gender, pTNM stage, tumor size, number of nodules, vascular invasion, incidental tumors, adjuvant chemotherapy, preoperative chemoembolization, alpha-fetoprotein (AFP) tumor marker, lobar distribution, and histological grade. Overall OLT survival of HCV patients diagnosed with concomitant HCC was significantly lower when compared to patients who underwent OLT for HCV alone at 1, 3, and 5 years (75%, 71%, and 55% versus 84%, 76%, and 75%, respectively; P < 0.01). Overall survival of patients with stage I HCC was significantly better than patients with stage II, III, or IV (P < .05). Eleven of 67 patients developed tumor recurrence. Sites of recurrence included transplanted liver (5), lung (5), and bone (1). Twenty-four of 67 patients (36%) died during the follow-up time. Causes of deaths included recurrent HCC in 8 of 24 patients (12%) and recurrent HCV in 3 of 24 patients (4.5%), whereas 13 (19.5%) patients died from causes that were unrelated to HCV or HCC. Both univariate and multivariate analysis demonstrated that pTNM status (I versus II, III, and IV; P < .05) was a reliable prognostic indicator for patient survival. Presence of vascular invasion (P = .0001) and advanced pTNM staging (P = .038) increased risk of recurrence. Multivariate analysis showed that pretransplant chemoembolization and adjuvant chemotherapy reduced risk of death after OLT in HCC recipients. In conclusion, this study demonstrates the effectiveness of OLT for patients with HCC in a large cohort of chronic HCV patients. Advanced tumor stage, and particularly vascular invasion, are poor prognostic indicators for tumor recurrence. Early pTNM stage, adjuvant chemotherapy, and preoperative chemoembolization were associated with positive outcomes for patients who underwent OLT for concomitant HCV and HCC.     

影响原发性肝癌肝移植治疗的预后因素分析

目的分析影响肝癌肝移植术后生存率和无瘤生存率的危险因素,探讨国内肝移植治疗肝癌的选择标准。方法对67例接受同种异位原位肝移植治疗的原发性肝癌病人的基本资料和肿瘤相关资料包括术前病情分级、血清AFP水平、术前辅助治疗以及肝癌大小、数目、pTNM分期、肿瘤恶性程度分级等因素进行单因素和多因素分析。结果术后1年、2年累积生存率为77%、67%,6个月和12个月无瘤生存率为66%和58%。单因素分析显示对肝癌肝移植术后累积生存率影响有统计学意义的因素为CHILD分级(MELD积分)和肝外大血管侵犯;多因素分析影响肝癌肝移植术后无瘤生存率有统计学义的因素是肿瘤大小、大血管侵犯和肿瘤分化程度。结论影响肝癌肝移植术后生存率的因素仍是术前患者肝功能状态。对存在大血管侵犯的肝癌患者需严格控制肝移植术适应证,而无血管侵犯的患者在选择肝移植治疗时肿瘤大小指标可较米兰标准适当放宽。     

Adjuvant chemotherapy improves survival after liver transplantation for hepatocellular carcinoma.

OBJECTIVE: The aim of this study was to evaluate the effect of postoperative adjuvant chemotherapy on the recurrence rate and survival of patients after orthotopic liver transplantation (OLT) for hepatocellular carcinoma (HCC). SUMMARY BACKGROUND DATA: Historically, liver transplantation for HCC has yielded poor long-term survival. Multimodality therapy has been initiated in an effort to improve survival statistics. METHODS: Twenty-five patients were placed on 6 months of intravenous fluorouracil, doxorubicin, and cisplatin after OLT. Risk factors, recurrence rates, and survival rates were analyzed and compared with historic controls. RESULTS: Overall long-term survival in the protocol patients was 46% at 3 years, improved over our historic controls of 5.8% at 3 years (p = 0.0001). Overall recurrence rate was 20% (n = 4). Possible risk factors, such as tumor size, vascular invasion, multifocality, capsular invasion, and tumor differentiation, were not found to be significantly predictive of survival. Three patients with long-term, disease-free survival had tumors > 5 cm. Side effects from chemotherapy were common, but rarely severe. CONCLUSIONS: This study suggests that adjuvant chemotherapy after transplantation for HCC can provide long-term cure and may improve survival, even in patients with stage III and IV disease.     

Liver Transplantation for Malignant Diseases: Selection andPattern of Recurrence

Liver transplantation (LT) for malignant tumors should be accepted if, with adequate case selection, long-term results are similar to those in patients transplanted for benign diseases. The aim of the present study was to reexamine selection criteria for LT in malignant diseases with particular emphasis on hepatocellular carcinoma (HCC) in cirrhosis. One hundred-three of 369 patients transplanted in our unit had HCC in cirrhosis (28%), 15 of which were incidental tumors, and 234 patients underwent LT for non-cholestatic cirrhosis. Pretransplant arterial chemoembolization(TACE) was performed in 36 cases (41%) of known HCC. Only early,well-delimited tumors in advanced cirrhosis with no extrahepatic disease were accepted for LT. Hepatocellular carcinoma characteristics included mean tumor size (3.1 cm), multiple (59%), bilobular involvement (31%), and vascular invasion (9.2%). Postoperative mortality was 4%. Median follow-up was 67.5 months. Tumor recurrence rate was 14.5%, 33% (5/15) in incidental tumors and 11.4% (10/88) in known HCC and by tumor stage (pTNM): 7.7% (1/13) in stage I, 16.7%(5/30) in stage II, 15% (3/20) in stage III, and 17% (6/35) in stage IV. Mean time for recurrence was 20.6 months. Tumoral vascular invasion, tumor differentiation, and satellite tumors were significant factors for tumor recurrence in univariate analysis, whereas tumor vascular invasion was the only significant factor for tumor recurrence in multivariate analysis. Actuarial survival rates at 1, 3, and 5 years were 81%, 66%, 58%, respectively, in patients with HCC and were similar to those of cirrhotic patients 76%, 67%, 63%, respectively.In conclusion, patients with early HCC in cirrhosis are good candidates for LT; results are similar when compared with those of cirrhotic patients without tumor. Liver transplantation for other malignancies is admitted only in fibrolamellar hepatoma, hepatoblastoma, epithelioid hemangioendothelioma without extrahepatic disease, and in metastases from carcinoid tumors.     

原发性肝细胞癌肝切除术后短期复发的危险因素

目的 探讨影响原发性肝细胞癌(HCC)患者肝切除术后短期复发的危险因素.方法 回顾性分析1997年1月至2008年12月接受肝切除术的502例HCC患者术后1～2个月的评估结果与无瘤生存率和总体生存率的关系.其中男性419例,女性83例,年龄14～82岁,平均54岁.结果 综合术中所见、病理学检查、随访和术后2个月评估的结果,显示术中肉眼可见血管癌栓、姑息切除、切缘病理阳性、区域淋巴结转移、术后血清甲胎蛋白(AFP)持续阳性、术后1个月经导管肝动脉化疗栓塞术(TACE)肿瘤血管染色并在1个月后肝脏CT扫描相应区域有碘油沉积(TACE阳性)和术后1个月肺转移是短期复发的危险因素,其中位无瘤生存时间＜6个月.高危组(n=106)的1、2、5年总体生存率为52%、25%、8%,无瘤生存率为22%、9%、3%;非高危组(n=396)的1、2、5、10年总体生存率为97%、85%、56%、35%,无瘤生存率为84%、67%、42%、31%.高危组患者大多数为大肝癌、分化程度较差、肿瘤侵及肝包膜和伴有卫星灶者,TNM分期大多数处于Ⅲ、Ⅳ期.结论 术中肉眼可见血管癌栓、姑息切除、切缘病理阳性、区域淋巴结癌转移、术后血清AFP值持续阳性、术后TACE阳性和术后1个月肺转移是HCC肝切除患者短期复发的危险因素,具有这些危险因素之一时意味着肿瘤残留,应采取针对性的治疗措施以达到消灭肿瘤、延长总体生存期的目的.

Abstract：

Objective To analyze the high risk factors for tumor recurrence in short term after hepatectomy for the patients with primary hepatocellular carcinoma (HCC). Methods Five hundreds and two patients with primary HCC underwent hepatectomy were included from January 1997 to December 2008.Among these patients,males were 419 cases and females were 83 cases. The age was 14 to 82 years (average age 54 years). The results of evaluation on 2 months after resection and tumor recurrence and survival were analyzed. Results According to the operative and pathologic findings and the evaluation on 2 months after hepatectomy, the patients with vascular invasion, palliation resection,cutting edge pathologic residual tumor,lymph notes metastasis,serum AFP level continuing higher after resection or (and) positive TACE (tumor dyeing on TACE within 1 month and a deposit of lipiodol on CT scan) were high risk factors (high-risk group, 106 cases,21.1%) ,the recurrence-free survival was 22% ,9% and 3% (1,2 and 5 year) and overall survival was 52% , 25% and 8%. On the non-high risk group patients, the recurrence-free survival was 84% ,67%, 42% and 31% (1,2, and 5 year) and overall survival was 97% ,85%, 56% and 35%. The bigger tumor,poor differentiation,tumor invading to liver capsule, satellite focus and TNM Ⅲ-Ⅳ stage in high-risk groups were more significantly than that in non-high-risk groups. Conclusion The vascular invasion, palliation resection,cutting edge pathologic residual tumor, lymph notes metastasis, serum AFP level continuing higher or (and) positive TACE within 2 months after resection are high risk factors for HCC patients in short term after hepatectomy,which mean tumor remnant.     

Liver transplantation for hilar cholangiocarcinoma: Spanish experience

INTRODUCTION: Palliative treatment for nondisseminated irresectable hilar cholangiocarcinoma (HCC) carries a 0% 5-year survival rate. The role of orthotopic liver transplantation (OLT) in these patients is controversial because the survival rate is lower than that for other indications for transplantation and the lack of available donor organs. The aim of this paper was to review the Spanish experience in OLT for HCC and identify prognostic factors for survival. METHODS: We retrospectively reviewed 36 patients undergoing OLT for HCC over 13 years. RESULTS: The actuarial survival rate at 1, 3, and 5 years was 82%, 53%, and 30%, respectively. The main cause of death was tumor recurrence (53%). In the univariate analysis, the factors for a poor prognosis were vascular invasion (P<.001) namely 0% survival at 3 years when present versus 63% and 35% at 3 and 5 years, respectively, when it was not; and stages III to IVA (P<.05), namely 15% survival at 5 years versus 47% for stages I to II. Lymph node and perineural invasion also reduce survival. In the multivariate analysis, the factors for poor prognosis included vascular invasion (P<.01) and stages III to IVA (P<.01). CONCLUSION: OLT for nondisseminated irresectable HCC has higher survival rates at 3 and 5 years than palliative treatments, especially with initial stage tumors, which means that more information is needed to better select cholangiocarcinoma patients for transplantation.     

肝癌临床病理因素与肝移植术后肿瘤复发的关系

目的探讨原发性肝细胞型肝癌患者行原位肝移植后肝癌复发或转移的影响因素。方法回顾性分析31例肝细胞型肝癌患者肝移植的临床资料,探讨临床病理因素与术后肿瘤复发或转移及无瘤存活率的关系。结果31例患者术后随访时间为12~24个月,中位随访时间为15个月,6个月、12个月及18个月的无瘤存活率分别为83.87%、74.19%及59.49%。Child-Pugh分级、肿瘤的数目、病理Edmondson分级对肿瘤的复发或转移无影响;肿瘤的大小、TNM分期、有无脉管浸润、是否符合Milan标准对肿瘤的复发或转移有显著影响;肿瘤有无脉管浸润以及TNM分期对患者的无瘤存活率有显著影响。结论肿瘤的大小、TNM分期、有无脉管浸润、是否符合Milan标准均能反映肿瘤复发的风险,而肿瘤的TNM分期及肿瘤有无脉管浸润能进一步影响患者术后的无瘤存活率。     

Complete Necrosis After Transarterial Chemoembolization Could Predict Prolonged Survival in Patients with Recurrent Intrahepatic Hepatocellular Carcinoma After Curative Resection

Background

We explored the predictors of response to transarterial chemoembolization (TACE) in patients with recurrent intrahepatic hepatocellular carcinoma (HCC) after hepatectomy and investigated the survival of these patients according to the response to TACE.

Methods

We analyzed data from 199 consecutive HCC patients who underwent curative liver resection and who later received repeat TACE for intrahepatic HCC recurrence.

Results

Of 199 patients, 139 (69.8%) achieved complete necrosis (CN) of HCC after repeated TACE (mean TACE session number, 1.3) and the other 60 (30.2%) (non-CN group) did not achieve CN. At hepatectomy, the CN group showed significantly smaller proportions of tumor capsular invasion, microvascular invasion, and pathologic tumor–node–metastasis stage III or IV HCCs. At first TACE, the CN group showed a significantly greater proportion of patients with time to recurrence ≥ 1 year, Child–Pugh class A, serum alpha-fetoprotein (AFP) levels < 200 ng/mL, tumor size < 3 cm, solitary tumors, and nodular tumor types; portal vein invasion were less common than seen in the non-CN group. After multivariate analysis, tumor size < 3 cm and a single tumor at first TACE were independently related to attainment of CN after TACE. Median survival after first TACE was significantly longer in the CN group (48.9 versus 17.0 months). In a Cox regression model, CN after TACE was an independent predictor of favorable survival outcome after first TACE.

Conclusions

CN after repeat TACE for postresection intrahepatic recurrence was attained more commonly in patients with smaller tumor size and lower tumor number at first TACE and favored longer survival in recurrent patients.     

Recurrent hepatocellular carcinoma after liver transplantation – an emerging clinical challenge

In western countries, hepatocellular carcinoma (HCC) is a major reason for orthotopic liver transplantation (OLT) with estimated recurrence rates between 15% and 20%. This selective literature review addresses follow‐up care after OLT in HCC and current treatment options. Recurrence prediction is based on pathological tumor stage, vascular invasion, serum alfafetoprotein levels, and histological differentiation, but further advances are expected by molecular profiling techniques. Lower levels of immunosuppressive agents are associated with a lower risk for HCC recurrence. Retrospective studies indicate that mammalian target of rapamycin (mTOR) inhibitors as immunosuppression reduce the risk of HCC recurrence. However, prospective studies supporting this potential advantage of mTOR inhibitors are still lacking, and higher rejection rates were reported for sirolimus after OLT in HCC. Prognosis is poor in recurrent HCC, a longer interval between OLT and recurrence and feasibility of surgical resection are associated with improved survival. Systemic treatment with sorafenib is the current standard of care in patients with advanced‐stage HCC not suitable for locoregional therapy. After OLT, combination of an mTOR inhibitor with sorafenib is feasible and frequently used in clinical practice. As safety and efficacy data are still limited, close clinical monitoring is mandatory.     

Beyond Milan criteria – chances and risks of expanding transplantation criteria for HCC patients with liver cirrhosis

Abstract:  Orthotopic liver transplantation (OLT) is, apart from resection, one important curative treatment for hepatocellular carcinoma (HCC) in liver cirrhosis, and especially attractive because it eliminates both the tumor and the underlying liver disease. The application of restrictive inclusion criteria for OLT in HCC patients resulted in favorable long-term recurrence-free survival. These criteria, however, exclude a subgroup of patients which, despite advanced tumor size, demonstrate an acceptable outcome. As a consequence, expansion of the strict Milan criteria has been discussed. However, this will also deteriorate the average outcome of OLT in HCC patients. Considering that we run short of donor organs, more sophisticated prediction models for survival after OLT for HCC patients are needed to identify patients who benefit best from OLT. Neoadjuvant treatment that is frequently applied as a bridging technique for patients on the waiting list for OLT could provide useful information on tumor behavior to better predict the risk of post-OLT tumor recurrence. This might also allow expansion of the Milan criteria to patients with good response to downstaging methods without negatively affecting post-OLT survival. Furthermore, alternative scoring systems have been suggested to identify HCC patients that might still benefit from resection instead of OLT, and molecular tools are being explored to provide predictive information on HCC biology. This review discusses the advantages and risks of extended inclusion criteria for OLT and the currently available data on alternative prediction models and bridging methods in HCC patients.     

Impact of Tumor Characteristic on the Outcome of Liver Transplantation in Patients With Hepatocellular Carcinoma

Introduction

Orthotopic liver transplantation (OLT) is a well-established treatment for cirrhotic patients with hepatocellular carcinoma (HCC) who meet the Milan criteria. The aim of this study was to identify predictors of survival among 65 patients with HCC in cirrhotic livers who underwent liver transplantation (OLT).

Methods

From January 2001 to December 2008, we performed 655 OLT in 615 patients. HCC was diagnosed in 58 patients before OLT and in 65 by histological examination of the explanted livers; 74% of the patients met Milan criteria by histological examination.

Results

The median follow-up was 27 months (range = 1-96). We analyzed patient age and gender, etiology of liver disease, Child score at transplantation, rejection episodes, tumor number/size, vascular invasion, and differentiation grade. There was no significant difference in survival among patients grouped according to the Model for End-stage Liver Disease staging system for HCC. The 5-year survival of patients with low differentiated (G3) HCC was significantly worse than that of those with moderately differentiated (G2) or well-differentiated (G1) HCC: 50%, 81%, and 86% respectively, (P < .01). Patients with microvascular invasion displayed a worse 5-year survival than those without vascular invasion (42% vs 80%; P < .01).

Conclusions

The analysis indicated that the histological grade of the tumors and evidences of microscopic vascular invasion were the most useful predictive factors for overall survival among patients with cirrhosis after liver transplantation for HCC.     

Multifocal manifestation does not affect vascular invasion of hepatocellular carcinoma: implications for patient selection in liver transplantation

BACKGROUND AND AIMS: Liver transplantation (OLT) for hepatocellular carcinoma (HCC) improves patient survival when tumor size and number are limited according to the Milan criteria. However, the impact of tumor size vs. the number of lesions for tumor recurrence after OLT is unclear. Microvascular invasion appears to be a significant risk factor for tumor recurrence. Therefore, it was the aim of this study to investigate tumor differentiation and microvascular invasion in relation to tumor number and size and their impact on survival after transplantation. PATIENTS AND METHODS: In 97 adult HCC patients who underwent OLT between June 1985 and December 2005 the incidence of microvascular invasion, tumor differentiation, and the number and size of tumor lesions were analyzed retrospectively. Their impact on survival was studied by multivariate analysis. RESULTS: Microvascular invasion was the only independent negative predictor of survival after OLT for HCC (p = 0.025). Tumor size > 5 cm was predictive for microvascular invasion (p = 0.007). In contrast, tumor number did not affect the incidence of microvascular invasion or cumulative survival. CONCLUSION: The size of the largest HCC lesion, but not the number of tumors, determined microvascular invasion, a predictor of the outcome following OLT for HCC. Thus, the number of HCC lesions should not be applied to patient selection prior to OLT. These data support the extension of the Milan criteria for the selection of HCC patients for OLT with regard to tumor number, but not tumor size.     

肝癌患者肝移植前行TACE治疗的效果及其对肝移植预后的影响

目的 探讨肝癌患者肝移植前行肝动脉介入栓塞化疗(TACE)的效果及其对肝移植预后的影响.方法 共有67例肝癌患者在施行肝移植前接受了TACE治疗,其中男性52例,女性15例,年龄34～67岁,平均48岁;符合米兰标准者61例,超出米兰标准6例.肝移植术式采用经典原位肝移植62例,背驮式肝移植5例.术后免疫抑制方案采用他克莫司(或环孢素A、或西罗莫司)+吗替麦考酚酯+糖皮质激素.根据术后病肝的组织病理学检查结果,判断TACE的治疗效果,并比较TACE治疗效果不同者间术后1年和2年肿瘤复发率及存活率.结果 肿瘤结节坏死50%以上者有50例,其中新生肿瘤结节者2例,经TACE治疗后肿瘤结节坏死率为73.77%.肿瘤结节坏死50%以下者有17例,其中新生肿瘤结节者7例.TACE治疗效果良好和无新生肿瘤结节者48例,其移植后1年和2年肿瘤复发率分别为2.08%(1/48)和6.25%(3/48),存活率分别为97.92%(47/48)和95.83%(46/48);TACE治疗较差且发现新生肿瘤结节者19例,其移植后1年和2年肿瘤复发率分别为36.84%(7/19),和57.89%(11/19),存活率分别为73.68%(14/19)和47.37%(9/19),二组各数据相比较,差异均有统计学意义(P＜0.05).结论 TACE可以较好的局部控制肝癌,但对于术前未发现的肿瘤结节影响有限.移植前接受TACE治疗效果较好者,其预后也较好,TACE治疗的效果可以作为判断肝移植预后的一个指标.     

Liver transplantation in patients with hepatocellular carcinoma: one center's experience

Hepatocellular carcinoma (HCC), which worldwide is the fifth most common malignancy in men and the ninth most common malignancy in women, accounts for 6% of all malignant lesions. We evaluated our results of liver transplantation for patients with HCC. Between January 2004 and April 2007, 31 patients (5 females, 26 males; age range, 1.1-65 years) with preoperatively or incidentally diagnosed HCC underwent orthotopic liver transplantation (OLT) at our center. Eleven grafts were from deceased donors, and 20 from living-related donors. Inclusion criteria were no invasion of a major vascular structure and no evidence of extrahepatic disease. In 17 patients, tumors exceeded the Milan criteria. According to the tumor-node-metastasis staging system, 6 patients had stage 1, 8 had stage II, 2 had stage III, and 15 had stage 4A carcinoma. Three complications occurred in 31 patients: hepatic arterial thrombosis in 1 patient and biliary leakage in 2. At a mean follow-up of 24.3 +/- 12.5 months, 29 patients are well with excellent graft function. Two patients died at 23 and 17 months after OLT respectively. The longest graft survival is 43 months. There have been 4 tumor recurrences, namely, at 4, 26, 24, and 29 months after OLT, respectively. Patient and disease-free survival rates are 93.5% and 90%, respectively. In conclusion, OLT provided long-term disease-free survival for patients with HCC, even those with locally advanced tumors who had no effective alternative treatment than transplantation.     

Multimodality treatment for patients with hepatocellular carcinoma: Analysis of prognostic factors in a single western institution series

There are few Western studies evaluating prognostic factors for survival in patients with hepatocellular carcinoma (HCC) and the influence on survival of various therapeutic options including ortbotopic liver transplantation (OLT). A retrospective analysis was performed of 122 patients with HCC treated at the University of Alabama at Birmingham from January 1990 through December 1999. Clinicopathologic and treatment factors were analyzed with overall survival as the main outcome variable. Median age was 62 years. Most patients were male (74%) and white (79%). Eighty patients (66%) had associated cirrhosis. Sixty-three percent of patients presented with American Joint Committee on Cancer (AJCC) stage III or lV tumors. The median follow-up for survivors was 22 months. The l-, 3-, and 5-year actuarial survival rates for the entire cohort were 46%, 24%, and 17%, respectively. On multivariate analysis, ablative surgery (P = 0.003), AJCC stages I and II (P = 0.0012), and absence of vascular invasion (P = 0.0001) were found to be independent favorable characteristics. Forty-four patients underwent surgical resection (including OLT, n = 20) or a surgical ablative procedure. All but two nonsurgical patients died of disease. The actuarial l-, 3-, and S-year survival rates for this group were 80%, 71%, and 61%, respectively. On multivariate analysis of the surgical group, only vascular invasion was associated with poor prognosis (P = 0.001). OLT was associated with a favorable prognosis on univariate analysis (P = 0.02). Forty percent of patients who received transplants underwent local/regional treatment before transplantation and the outcome in these patients was no different from that in other transplant patients. Surgical treatment is the only potential curative option for HCC, and qualifying for liver transplantation may be a favorable prognostic factor in surgical patients. Local/regional therapy prior to transplantation may provide a bridge to OLT without an increase in tumor-related mortality.     

Impact of histological grade of hepatocellular carcinoma on the outcome of liver transplantation

HYPOTHESIS: Histological grade of hepatocellular carcinoma (HCC) is an important prognostic factor affecting patient survival after orthotopic liver transplantation (OLT). DESIGN: Retrospective analysis. SETTING: University-based teaching hospital. PATIENTS: Of 952 OLTs performed between June 1991 and January 1999, 56 OLT recipients had histologically proven HCC in the explant liver. Of those, 53 patients with complete clinicopathologic data were analyzed. A single pathologist blinded to the outcome of each patient reviewed all histological specimens. RESULTS: Median follow-up was 709 days. Overall survival for patients with tumors sized 5 cm or less at 1, 3, and 5 years was 87%, 78%, and 71%, respectively (Kaplan-Meier). Univariate analysis revealed the size, number, and distribution of tumors; the presence of microscopic vascular invasion and lymph node metastasis; histological differentiation; and pTNM stage to be statistically significant factors affecting survival. Multivariate analysis revealed histological differentiation and pTNM stage to be the independent and statistically significant factors affecting survival (P =.002 and.03, respectively). When pTNM stage was excluded from multivariate analysis, histological differentiation and size remained the significant independent factors (P =.02 and.03, respectively). Three-year survival for patients with small (5 cm) tumor with well- to moderately differentiated and poorly differentiated HCC was 62.5% and 0%, respectively. CONCLUSIONS: In our retrospective experience, histological differentiation had a statistically significant effect on the prognosis of HCC after OLT. However, before altering the current OLT selection criteria for patients with HCC, prospective studies are required to confirm the impact of histological grade on clinical outcome.     

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).     

Long-term results of liver transplantation for hepatocellular carcinoma: an update of the University of Padova experience

BACKGROUND: Hepatocellular carcinoma (HCC) competes with benign liver disease as indication for liver transplantation (OLT). The aim of this study was to determine long-term results of OLT for HCC. METHODS: We retrospectively analyzed the prognostic role of HCC diagnosis at pathological exam in adult OLT. In the HCC group, we evaluated the prognostic role of the time of diagnosis (incidental versus nonincidental) and of pathological tumor TNM staging. The primary endpoint was 1-, 3-, and 10-year patient survivals. RESULTS: From 1991 to 2006, among 550 adults who underwent first OLT, HCC was found in 120 patients at pathological exam. In 26 cases (22%), the diagnosis of HCC was incidental. There were 59 cases (49%) of pathological T1 to T2 tumor (one nodule < 5 cm, or two to three nodules < 3 cm, without metastases and/or vascular invasion), and 61 cases (51%) of pathologic T3-T4a tumor. HCC diagnosis did not show a significant prognostic impact by Cox survival analysis. After a median follow-up of 31 months, 1-, 5-, and 10-year survivals were 91%, 81%, and 73% in the HCC group, and 84%, 76%, and 67% in the non-HCC group. Time of HCC diagnosis (incidental versus nonincidental) and pathological TNM staging (T1 to T2 vs T3 to T4a) did not result significant survival predictors upon Cox analysis. CONCLUSION: In our experience, the long-term results of OLT for HCC overlapped those of OLT for benign disease, although 51% of tumors were T3 to T4a at pathological exam.     

Resection or transplantation for hepatocellular carcinoma in cirrhotic patients: outcomes based on indicated treatment strategy

BACKGROUND: Surgical resection has been the treatment of choice for hepatocellular carcinoma (HCC), but the resection rate remains low in cirrhotic patients and recurrence is common. Unfavorable results compared with benign disease and the shortage of organ donors have led to a restricted indication for orthotopic liver transplantation (OLT) for HCC. STUDY DESIGN: The aim of this study was to analyze the results of our surgical approach to HCC in patients with cirrhosis. The first treatment strategy indicated in these patients was OLT. From January 1990 to May 1999, 85 patients underwent OLT and the remaining 35 had surgical resection. RESULTS: One-, 3-, and 5-year survival rates were 84%, 74%, and 60% versus 83%, 57%, and 51%, respectively, in the OLT and resection groups (p = 0.34). Hepatic tumor recurrence was much less frequent in the OLT group than in the resection group. The 1-, 3-, and 5-year disease-free survival rates were 83%, 72%, and 60% versus 70%, 44%, and 31%, respectively (p = 0.027). In the multivariate Cox regression analysis, macroscopic vascular invasion was the only factor independently associated with death or recurrence after OLT (p = 0.006). After partial liver resection, the tumors significantly associated with mortality and recurrence in the multivariate analysis were solitary or multiple tumors greater than 2cm with microscopic vascular invasion (pathologic pT3) (p = 0.01). CONCLUSIONS: Our results confirm that in cirrhotic patients, OLT may provide better outcomes than liver resection in carefully selected HCC and that longterm survival is similar to the results of OLT in cirrhotic patients without tumors.     

Factors Affecting Survival and Tumor Recurrence in Patients Transplanted for Hepatocellular Carcinoma and Coexistent Hepatitis C Virus

A better understanding of tumor factors influencing patient and graft survival and recurrence of hepatocellular carcinoma (HCC) associated with hepatitis C virus (HCV) cirrhosis may be useful to maximize the benefits of liver transplantation (OLT). Sixty-three adults underwent OLT for end-stage liver disease secondary to HCV with concomitant HCC. The outcome measures were patient and graft survival, as well as recurrence-free survival, computed using a stepwise Cox proportional hazards regression analysis. Kaplan-Meier 1-, 3-, and 5-year patient survival rates were 82%, 80%, and 69%, respectively, they were better for incidentally discovered HCC compared with preoperatively diagnosed HCC (P = .04). The overall recurrence-free survival rates were 81%, 76%, and 61% at 1, 3, and 5 years, respectively. Univariate analysis showed that nonincidental HCC (P = .04), pTNM stage (P = .012) and vascular invasion (P = .003) correlated with recipient mortality. Vascular invasion (odds ratio [OR] = 2.12; P = .001) and pTNM (OR = 1.50; P = .008) were independent predictors of overall survival. A combination of tumor vascular invasion with advanced pTNM was associated with a dismal prognosis (log-rank = 21.89; P = .0001). Tumor grading (OR = 1.2; P = .04), pTNM (OR = 3.7; P = .001) and vascular invasion (OR = 1.6; P = .002) were independent predictors of recurrence. In conclusion, advanced pTNM and the presence of vascular invasion are strong predictors of poor survival and tumor recurrence.