Superiority of transplantation versus resection for the treatment of small hepatocellular carcinoma.

The best therapy for hepatocellular carcinoma (HCC) is still debated. Hepatic resection (HR) is the treatment of choice for single HCC in Child A patients, whereas liver transplantation (LT) is usually reserved for Child B and C patients with single or multiple nodules. The aim of this study was to compare HR and LT for HCC within the Milan criteria on an intention-to-treat basis. Forty-eight patients were treated by LT and 38 by HR. The median time on the waiting list for transplantation was 118 days. The estimated overall survival was significantly higher (P = 0.005) in the LT group than in the HR one. The estimated freedom from recurrence was also significantly higher (P < 0.0001) for LT patients than for HR ones. Indeed, the probability of HCC recurrence after resection was higher than after transplantation achieving 31% and 76% for HR and 2% and 2% for LT at 3 and 5 years after surgery. Multivariate analysis confirmed that transplantation was superior to resection in terms of patient's survival and risk of HCC recurrence. We conclude that LT is superior to HR for small HCC in cirrhotic patients assuming that LT should be performed within 6-10 months after listing to reduce the dropouts for reasons of tumor progression.     

First-line liver resection and salvage liver transplantation are increasing therapeutic strategies for patients with hepatocellular carcinoma and child a cirrhosis

AIM: The present study focused on nine patients with hepatocellular carcinoma (HCC) associated with Child A liver cirrhosis undergoing first-line liver resection and salvage liver transplantation (SLT) for liver tumor recurrence. PATIENTS AND METHODS: Forty-six patients with HCC underwent liver transplantation (OLT); 37 (80.5%) were primary liver transplantations (PLTs) and 9 (19.5%) were SLTs. All patients who underwent SLT received minor transabdominal liver resections. RESULTS: The posttransplant 1-, 3-, and 5-year overall survival rates for SLT (88.9%, 88.9%, and 88.9%) were similar to those for PLT (78%, 62.7%, and 62.7%). Four (10.8%) patients in the PLT group had HCC recurrence, while there was zero recurrence in the SLT group. The 1-, 3-, 5-year disease-free survival rates for PLT (89%, 74%, and 74%) were similar to those for SLT (100%, 100%, and 100%). The 1-, 3-, 5-year disease-free survival rates after PLT were 89%, 74%, and 74%, and after SLT were 100%, 100%, and 100%, respectively. The operative mortality, intraperioperative bleeding, operative time, intensive care unit stay, in-hospital stay, and overall incidence of postoperative complications were similar in the two groups. CONCLUSIONS: In our experience, SLT for HCC is a feasible procedure with similar results in terms of overall survival, disease-free survival, and postoperative complications to those reported for patients who underwent PLT at our institute. An important role exists for SLT as shown by the fact that such a strategy has been used in the 20% of the patients undergoing OLT for HCC.     

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.     

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.     

Small hepatocellular carcinoma in Child A cirrhotic patients: Hepatic resection versus transplantation

Hepatic resection (HR) is the treatment of choice for small hepatocellular carcinoma (HCC) in a noncirrhotic liver, whereas liver transplantation (LT) offers better results in patients with impaired hepatic function (Child B and C). However, it is still debated whether HR or LT is the best strategy for patients with Child A cirrhosis. We conducted a retrospective study on 37 consecutive patients with Child A cirrhosis and small HCC, treated between 1991 and 1999. Seventeen of these patients, who underwent LT, were compared with 20 patients who underwent HR, and prognostic factors for survival and tumor recurrence were analyzed. The primary endpoints were the intention-to-treat, 3- and 5-year survival, and 3- and 5-year recurrence-free survival. Three- and 5-year patient survival rate both were significantly (P = .04) higher in the LT group (87% and 71%, respectively) than in the HR group (67 and 36% respectively). Similarly, the 3- and 5- year recurrence-free survival rates were 87% and 80% for the LT group, and 52% and 40% for the HR group (P = .03). Absence of microscopic vascular invasion was the only other prognostic factor correlated with significantly better recurrence-free survival (P = .02). Therefore, we concluded that in patients with Child A cirrhosis and small HCC, liver transplantation resulted in better overall and disease-free survival than HR. (Liver Transpl 2003;9:513-520.)     

肝移植治疗原发性肝癌60例

目的　评价肝移植治疗原发性肝癌的疗效和受体选择。方法　对 1993年 9月～ 2 0 0 2年 9月施行的 6 0例次肝癌肝移植患者的临床资料进行回顾性分析 ,比较不同时期肝癌肝移植的疗效和大、小肝癌的术后存活率。结果　 1993年 9月～ 2 0 0 0年 7月共实施肝癌肝移植 2 3例 ,1个月、1年、2年、3年存活率分别为 73 9%、6 0 9%、4 3 5 %和 2 9 0 %。 2 0 0 0年 8月～ 2 0 0 2年 9月共实施肝癌肝移植 37例 ,1个月、1年、2年存活率分别为 89 2 %、75 8%和 6 1 2 %。术前肝功能ClildA或B级受体的 1月存活率为 89 5 % ,较ClildC级的 72 7%差异有显著性意义 (P <0 0 5 )。大肝癌 4 1例 ,半数存活期为 18 0个月 ,1个月、1年、2年、3年存活率分别为 82 9%、6 3 1%、4 6 7%和 37 4 %。小肝癌 19例 ,存活期平均为 2 9 6个月 ,1个月、1年、2年、3年存活率分别为 84 2 %、76 6 %、6 5 6 %和6 5 6 % ,大、小肝癌累积存活率差异无显著意义。大、小肝癌的复发率分别为 2 7 7%和 15 8% ,获得长期存活的患者大部分生活质量良好。结论　肝移植是治疗原发性肝癌合并肝硬化的有效方法 ,对于明确合并有肝硬化门脉高压的小肝癌应提倡及时进行肝移植治疗 ,适当选择部分大肝癌作为移植受体仍有一定的合理性 ,血管侵犯或肝外     

Microvascular tumor embolism: independent prognostic factor after liver transplantation in hepatocellular carcinoma

Microscopic tumor cell dissemination may be a more important factor in the recurrence of hepatocellular carcinoma (HCC) after liver transplantation, probably because of posttransplant immunosuppression. The presence of microvascular tumor embolism was undetermined as a factor for HCC recurrence after orthotopic liver transplantation (OLT). This study evaluated whether microvascular tumor embolism affects recurrence-free survival and correlates with other clinicopathologic factors after OLT among patients with HCC. From September 1996 to June 2003, 72 OLTs for HCC were enrolled in this study. Median follow-up was 22.8 months. Among 41 patients without microvascular tumor embolism, 1-year, 2-year, and 5-year recurrence-free survival rates were all 97.6%, while these rates were 77.3%, 68.2%, and 59.7%, respectively, for 31 patients (43.1%) with microvascular tumor embolism (P = .0006). The 5-year recurrence-free survival rate showed significant differences for a pT2 tumor (P = .0073), for maximal tumor size <3 cm (P = .0328), for > or =5 cm solitary tumor (P = .0095), and for the presence of a tumor capsule (P = .0012), within the Milan criteria (P = .0376). At multivariate analysis, significant independent predictors for HCC recurrence were microvascular tumor embolism and histopathologic grade. In conclusion, microvascular tumor embolism is an independent predictor of HCC recurrence after liver transplantation. Although OLT is a safe and effective treatment for HCC within the Milan criteria, the presence of microvascular tumor embolism at pathologic examination can predict its recurrence. In these cases, the feasibility of immunosuppressive therapy or adjuvant chemotherapy must be considered to prevent tumor recurrence.     

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.     

ChildA级单个直径≤5cm肝细胞肝癌行肝移植与肝切除的预后比较

目的比较ChildA级、单个、直径≤5cm肝细胞肝癌行肝移植与肝切除术的预后。方法回顾性分析笔者所在医院肝移植中心2007～2011年期间行肝切除术及肝移植术的ChildA级、单个、直径≤5cm肝细胞肝癌患者的临床资料,比较2组患者术后无瘤生存率及总体生存率。结果本研究共纳入263例患者,其中肝移植组36例,肝切除组227例。肝移植组与肝切除组患者术后1、3及5年无瘤生存率分别为91．7％、85．3％及81．0％和80．6％、59．8％及50．8％,肝移植组高于肝切除组（P=-0．003）;术后1、3及5年总体生存率分别为100％、87．5％及83．1％和96．9％、83．8％及76．1％,2组间差异无统计学意义伊=0．391）。以肿瘤直径〈3em为标准再予以分析,其肝移植组与肝切除组术后1、3及5年无瘤生存率分别为92．3％、92．3％及92．3％和80．2％、62．5％及50．5％,肝移植组高于肝切除组（P=-0．019）;术后1、3及5年总体生存率分别为100％、91．7％及91．7％和97．7％、87．5％及79．5％,2组间差异也无统计学意义（p0．470）。结论ChildA级、单个、直径≤5cm肝细胞肝癌患者肝切除术后复发率高于肝移植,但两种治疗方式的术后总体生存率相似。     

Survival of cirrhotic patients with early hepatocellular carcinoma treated by percutaneous ethanol injection or liver transplantation.

For "early" hepatocellular carcinoma (HCC), surgery, orthotopic liver transplantation (OLT) and percutaneous ethanol injection (PEI) improve the natural history of the disease. We performed a retrospective study to evaluate the outcome of patients with cirrhosis and early HCC treated by PEI (n = 417) or OLT (n = 172). Overall, 589 patients with cirrhosis were studied. The proportion of patients in Child-Turcotte-Pugh (CTP) classes A, B, and C was 52.5%, 33.6%, and 13.9%, respectively. Most patients (78.9%) had solitary HCC. Overall 5-year and 10-year cumulative survival rates were 36.1% and 15.5% after PEI, and 66.3% and 49.1% after OLT, respectively (P < .0001). Overall 5-year and 10-year cumulative tumor-free survival rates were 25.3% and 18.0% after PEI, and 84.6% and 82.2% after OLT, respectively (P < .0001). When patients were sorted according to the severity of cirrhosis, mean survival times in PEI and OLT patients were 67 and 80 months in CTP class A (P = .05), 38 and 90 months in class B (P < .0001), and 31 and 95 months in class C (P = .0004). Similarly, mean tumor-free survival times in the 2 series of patients were 49 and 98 months in CTP class A (P < .0001), 39 and 121 months in class B (P < .0001), and 35 and 139 months in class C (P < .0001). In conclusion, this study challenges the therapeutic efficacy of PEI for patients with cirrhosis and early HCC, when compared to OLT: the proportion of both long-term survivors and tumor-free survivors was increased by OLT over PEI. The benefit of OLT extends to all patients, regardless of the degree of liver impairment.     

Liver transplantation criteria for hepatocellular carcinoma should be expanded: a 22-year experience with 467 patients at UCLA

OBJECTIVE: To assess the efficacy of orthotopic liver transplantation (OLT) for hepatocellular carcinoma (HCC) and the impact of current staging criteria on long term survival. SUMMARY BACKGROUND DATA: HCC is becoming an increasingly common indication for OLT. Medicare approves OLT only for HCCs meeting the Milan criteria, thus limiting OLT for an expanding pool of potential liver recipients. We analyzed our experience with OLT for HCC to determine if expansion of criteria for OLT for HCC is warranted. METHODS:: All patients undergoing OLT for HCC from 1984 to 2006 were evaluated. Outcomes were compared for patients who met Milan criteria (single tumor < opr =5 cm, maximum of 3 total tumors with none >3 cm), University of California, San Francisco (UCSF) criteria (single tumor <6.5 cm, maximum of 3 total tumors with none >4.5 cm, and cumulative tumor size <8 cm), or exceeded UCSF criteria. RESULTS: A total of 467 transplants were performed for HCC. At mean follow up of 6.6 +/- 0.9 years, recurrence rate was 21.2%, and overall 1, 3, and 5-year survival was 82%, 65%, and 52%, respectively. Patients meeting Milan criteria had similar 5-year post-transplant survival to patients meeting UCSF criteria by preoperative imaging (79% vs. 64%; P = 0.061) and explant pathology (86% vs. 71%; P = 0.057). Survival for patients with tumors beyond UCSF criteria was significantly lower and was below 50% at 5 years. Multivariate analysis showed that tumor number (P < 0.001), lymphovascular invasion (P < 0.001), and poor differentiation (P = 0.002) independently predicted poor survival. CONCLUSIONS: This largest single institution experience with OLT for HCC demonstrates prolonged survival after liver transplantation for tumors beyond Milan criteria but within UCSF criteria, both when classified by preoperative imaging and by explant pathology. Measured expansion of OLT criteria is justified for tumors not exceeding the UCSF criteria.     

肝癌患者术前HBV DNA定量水平与肝移植术后肝癌复发关系的探讨

目的 探讨肝癌肝移植患者术前乙型肝炎病毒(hepatitis B virus,HBV)DNA定量与肝移植术后原发性肝细胞癌(hepatocellular carcinoma,HCC)复发的关系.方法 回顾性分析2004年1月到2008年12月因同时合并HCC和HBV行肝移植手术并长期随访的148例患者,使用Kaplan-Meier生存分析统计患者生存率和无瘤生存率,根掘术后HCC是否复发将患者分成HCC复发组(43例)及未复发组(105例),使用COX多因素回归进行危险因素分析.结果 148例HCC肝移植患者1、3、5年生存率分别为86%,72%,72%,无瘤生存率分别为79%,71%,54%.肝移植术后HCC复发43例,复发率为29.1%(43/148),术后HCC平均复发时间为(13.16±14.17)个月(1～54个月).COX多因素回归分析表明超过米兰标准(HR=9.89;95%CI2.30～42.52;P=0.002)以及术前HBV DNA＞5log10 copies/ml(HR=2.26;95%CI1.01～5.04;P=0.047)是肝移植术后HCC复发的独立危险因素.结论 肝移植术前HBV DNA＞5log10 copies/ml和超过米兰标准是原发性肝癌患者肝移植术后HCC复发的高危因素.     

Liver transplantation outcomes for early-stage hepatocellular carcinoma: results of a multicenter study.

The incidence of hepatocellular carcinoma (HCC), a frequent and incurable complication of cirrhosis, continues to rise. Orthotopic liver transplantation (OLT) has been proposed as a treatment for unresectable, intrahepatic HCC limited in extent to the Milan criteria adopted by the United Network of Organ Sharing (UNOS) in 1998. More recently, somewhat less restrictive University of California, San Francisco (UCSF)10, criteria were proposed. To examine the long-term outcomes of OLT for HCC patients and to assess the UNOS policy of assigning weighted allocation points to patients with HCC, we retrospectively analyzed 144 patients (113 after 1998) with HCC who underwent OLT over an 11-year period at 3 institutions from UNOS Region 1. We compared their outcomes with 525 patients (272 after 1998) who underwent OLT for nonmalignant liver disease. The 1- and 5-year survival rates were 80.3% and 46.7%, respectively, for patients with HCC and 81.5% and 70.6%, respectively, for patients without HCC (P = .020). However, there was no difference in survival between HCC and non-HCC patients after implementation of disease-specific allocation for HCC in 1998. A higher proportion of the HCC cohort was older and male and had chronic HCV infection and alcoholic liver disease. In univariate analysis, having alpha-fetoprotein (AFP) levels of 10 ng/mL or less and meeting clinical and pathologic UCSF criteria were each significant predictors of improved survival (P = .005, P = .02, and P = .03, respectively). AFP greater than 10 ng/mL and exceeding pathologic UCSF criteria were also significant predictors of recurrence (P = .003 and P = .02, respectively). In conclusion, taken together, our data suggest that OLT is an acceptable option for patients with early HCC and that UCSF criteria predict outcome better than Milan or UNOS criteria. Regardless of which criteria are adopted to define eligibility, strict adherence to the criteria is important to achieve acceptable outcomes.     

Association between hepatitis B and hepatocellular carcinoma recurrence in patients undergoing liver transplantation

BACKGROUND/AIMS: Hepatitis B virus (HBV) and hepatocellular carcinoma (HCC) recurrences affect both patient and graft survivals post-orthotopic liver transplantation (OLT) in HBV patients with HCC. We analyzed the relationship between HBV and HCC recurrence in a large cohort of HBV-OLT patients with versus without HCC. METHODS: Two hundred eighty-seven HBV patients with OLT (72 also with HCC) were included in the study. Mean follow-up in the post-OLT period was 31.7 +/- 24.7 (range, 3-119) months. RESULTS: Post-OLT HBV recurrence observed in 10.1% of patients was more prevalent among the HCC group; 23.6% versus 5.5% in patients with and without HCC, respectively. The mean interval for the development of HBV recurrence was 39.5 +/- 28.5 (range, 2-99) months. Among 72 HCC patients, 8 patients (11.1%) had recurrent HCC, and 7 of them also had HBV recurrence. The mean interval for the development of HCC recurrence was 11.2 +/- 7.85 (range, 2-23) months after OLT. OLT patients with HCC with tumors exceeding the Milan criteria had worse 1-, 3-, and 5-year survival rates than patients with HCC meeting the Milan criteria. HBV and HCC recurrence-free survivals were significantly lower in patients with HCC and HBV recurrence, respectively. In the 7 patients with both HCC and HBV recurrence, mean HBV recurrence time was 9.42 +/- 6.75 months and mean HCC recurrence time was 9.57 +/- 6.75 months. There was a strong correlation between HBV and HCC recurrence times. Cox proportional hazards regression analysis showed that only HCC recurrence was a significant independent predictor of HBV recurrence (P < .001; hazard ratio [HR] = 26.94; 95% confidence interval [CI] = 10.81-67.11). On the other hand, HBV recurrence (P = .013; HR = 5.80; 95% CI = 1.45-23.17) and nodule count (P = .014; HR = 13.08; 95% CI = 1.70-100.83) were significant predictors of HCC recurrence. CONCLUSIONS: HBV and HCC recurrences demonstrate a close relationship in patients with OLT.     

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.     

The Impact of Pre-Operative Loco-Regional Therapy on Outcome After Liver Transplantation for Hepatocellular Carcinoma

No prior studies have shown that pre-operative loco-regional therapy for hepatocellular carcinoma (HCC) improves survival following orthotopic liver transplantation (OLT). We performed subgroup analyses according to pathologic HCC stage among 168 patients who underwent OLT to test the hypothesis that pre-operative loco-regional therapy confers a survival advantage in a subgroup at intermediate risk for HCC recurrence. Patients with pathologic T3 HCC meeting the proposed UCSF expanded criteria (single lesion not exceeding 6.5 cm or two to three lesions none > 4.5 cm with total tumor diameter within 8 cm) had a similar 5-year recurrence-free survival as patients with pathologic T2 HCC (88.5% vs. 93.8%; p = 0.56). In the subgroup with pathologic T2 or T3 HCC, the 5-year recurrence-free survival was 93.8% for the 85 patients who received pre-operative loco-regional therapy, versus 80.6% for the other 41 patients without treatment (p = 0.049). The treatment benefit, according to 5-year recurrence-free survival, appeared greater for pathologic T3 (85.9% vs. 51.4%; p = 0.05) than T2 HCC (96.4% versus 87.1%; p = 0.12). In conclusion, although the lack of a randomized controlled design precludes drawing firm conclusions, our results suggest that pre-operative loco-regional therapy may confer a survival benefit after OLT in the subgroup with pathologic T2 and T3 HCC.     

Radiofrequency ablation of small hepatocellular carcinoma in cirrhotic patients awaiting liver transplantation: a prospective study

OBJECTIVE: Determine the histologic response-rate (complete versus partial tumor extinction) after single radiofrequency ablation (RFA) of small hepatocellular carcinoma (HCC) arising in cirrhosis. Investigate possible predictors of response and assess efficacy and safety of RFA as a bridge to liver transplantation (OLT). BACKGROUND: RFA has become the elective treatment of local control of HCC, although histologic data supporting radiologic assessment of response are rare and prospective studies are lacking. Prognostic impact of repeated RFA for HCC persistence is also undetermined. METHODS: Percentage of RFA-induced necrosis and tumor persistence-rate at various intervals from treatment was studied in 60 HCC (median: 3 cm; Milan-Criteria IN: 80%) isolated in 50 consecutive cirrhotic patients undergoing OLT. Single-session RFA was the only treatment planned before OLT. Histologic response determined on explanted livers was related to 28 variables and to pre-OLT CT scan. RESULTS: Mean interval RFA-->OLT was 9.5 months. Post-RFA complete response rate was 55%, rising to 63% for HCC 3 cm (P = 0.05). Post-RFA tumor persistence probability increased with time (12 months: 59%; 18 months: 70%). Radiologic response rate was 70%, not significantly different from histology. Major post-RFA morbidity was 8%. No mortality, Child deterioration, patient withdrawal because of tumor progression was observed. Post-OLT 3-year patient/graft survival was 83%. CONCLUSIONS: RFA is a safe and effective treatment of small HCC in cirrhotics awaiting OLT, although tumor size (>3 cm) and time from treatment (>1 year) predict a high risk of tumor persistence in the targeted nodule. RFA should not be considered an independent therapy for HCC.     

Liver transplantation for hepatocellular carcinoma in patients without underlying liver disease: a systematic review.

Liver resection is the treatment of choice for hepatocellular carcinoma (HCC) occurring in the absence of underlying chronic liver disease. Orthotopic liver transplantation (OLT) is reserved for patients with unresectable disease but remains controversial. The aim of this study was to review the published literature on OLT for HCC in patients without coexisting chronic liver disease. A Medline-based search identified 126 patients reported in 16 papers over the last 32 years. One third had fibrolamellar HCC (FL-HCC), and two thirds had non-FL-HCC. Recurrence data were given in 55 patients of whom 27 had tumor recurrence. Seventy-five percent of the recurrences occurred within the first 2 years after OLT, although recurrences were reported up to 72 months after OLT for FL-HCC. The 5-year survival rate was greater in patients who underwent transplantation for FL-HCC than for non-FL-HCC (39.4% and 11.2%, respectively). There was insufficient information available to determine the influence of tumor size, distribution, stage, and vascular invasion on survival, although most patients in whom tumor characteristics were specified had advanced disease. This study indicates that FL-HCC carcinoma is a more favorable indication for OLT than non-FL-HCC in patients without underlying liver disease, although more detailed prognostic information is required to improve patient selection.     

Long-term survival and pattern of recurrence after resection of small hepatocellular carcinoma in patients with preserved liver function: implications for a strategy of salvage transplantation

OBJECTIVE: To evaluate the survival results and pattern of recurrence after resection of potentially transplantable small hepatocellular carcinomas (HCC) in patients with preserved liver function, with special reference to the implications for a strategy of salvage transplantation. SUMMARY BACKGROUND DATA: Primary resection followed by transplantation for recurrence or deterioration of liver function has been recently suggested as a rational strategy for patients with HCC 5 cm or smaller and preserved liver function. However, there are no published data on transplantability after HCC recurrence or long-term deterioration of liver function after resection of small HCC in Child-Pugh class A patients. Such data are critical in determining the feasibility of salvage transplantation. METHODS: From a prospective database of 473 patients with resection of HCC between 1989 and 1999, 135 patients age 65 years or younger had Child-Pugh class A chronic liver disease (chronic hepatitis or cirrhosis) and transplantable small HCC (solitary < or =5 cm or two or three tumors < or = 3 cm). Survival results were analyzed and the pattern of recurrence was examined for eligibility for salvage transplantation based on the same criteria as those of primary transplantation for HCC. RESULTS: Overall survival rates at 1, 3, 5, and 10 years were 90%, 76%, 70%, and 35%, respectively, and the corresponding disease-free survival rates were 74%, 50%, 36%, and 22%. Cirrhosis and oligonodular tumors were predictive of worse disease-free survival. Patients with concomitant oligonodular tumors and cirrhosis had a 5-year overall survival rate of 48% and a disease-free survival rate of 0%, which were significantly worse compared with other subgroups. At a median follow-up of 48 months, 67 patients had recurrence and 53 (79%) of them were considered eligible for salvage transplantation. Decompensation from Child-Pugh class A to B or C without recurrence occurred in only six patients. CONCLUSIONS: For Child-Pugh class A patients with small HCC, hepatic resection is a reasonable first-line treatment associated with a favorable 5-year overall survival rate. A considerable proportion of patients may survive without recurrence for 5 or even 10 years; among those with recurrence, the majority may be eligible for salvage transplantation. These data suggest that primary resection and salvage transplantation may be a feasible and rational strategy for patients with small HCC and preserved liver function. Primary transplantation may be a preferable option for the subset of patients with oligonodular tumors in cirrhotic liver in view of the poor survival results after resection.     

Results of resection and transplantation for hepatocellular carcinoma in cirrhosis and noncirrhosis

Hepatocellular carcinoma (HCC) is one of the most common cancers worldwide. Both liver resection (LR) and orthotopic liver transplantation (OLT) are surgical treatment options depending on the size of the tumor and the presence of cirrhosis. Liver cirrhosis is the main reason for the high early postoperative mortality after resection. Even in the Child A stage, extensive resections are not recommended. This study presented the results of surgical treatment (LR or OLT) for HCC in cirrhotic and noncirrhotic livers. We analyzed the data of 76 patients who underwent LR or OLT for HCC from January 2001 to December 2006. In noncirrhotic livers the following resections were performed: 30 right and extended right hemihepatectomies (54.5%); 11 left hemihepatectomies (20%); and 14 mono- or bisegmentectomies (25.5%). In cirrhotic livers the following procedures were performed: in Child A stage 1 right hemihepatectomy, 1 extended right hemihepatectomy, 1 extended left hemihepatectomy, and 4 mono- or bisegmentectomies; and in Child B stage, 3 mono- or bisegmentectomies. Among 11 patients who underwent transplantation, tumors in 2 patients exceeded the Milan criteria. Five patients in the LR group were treated with transarterial chemoembolization before transplantation. LR for HCC in cirrhosis should be performed with caution; there were no long-term survivors in our data. Our study confirmed that OLT shows good long-term survival in early HCC stages. However, this may also be true for stages above the Milan criteria. For HCC in noncirrhotic livers, LR remains the treatment of choice, justifying an extensive surgical approach. Such an approach achieved favorable long term survivals.