Waitlist Priority for Hepatocellular Carcinoma Beyond Milan Criteria: A Potentially Appropriate Decision Without a Structured Approach

Due to the risk of waitlist dropout from tumor progression, liver transplant candidates with hepatocellular carcinoma (HCC) within Milan criteria (MC) receive standardized exception points. An expansion of this process to candidates with HCC beyond MC has been proposed, though it remains controversial. This study sought to better define the utilization of exception points in candidates with HCC beyond MC and the associated outcomes. We reviewed all nonstandardized HCC applications that underwent formal regional review board evaluation between January 1, 2005 and March 2, 2011; 2184 initial HCC exception point applications were submitted. Of these, 41.9% fulfilled MC, 26.6% fulfilled University of California‐San Francisco (UCSF) criteria and 17.6% exceeded UCSF criteria. The majority of applications were accepted: 89.8% within UCSF and 71.2% beyond UCSF. There was a significantly (p < 0.001) higher risk of death on the waitlist or within 90 days of waitlist removal for candidates within UCSF (12.4%) or beyond UCSF (13.0%) criteria, compared to candidates with HCC within MC (6.0%). However, posttransplant outcomes were similar. While these results suggest increasing access to candidates with HCC beyond MC, comprehensive documentation of tumor characteristics and of successful downstaging is needed to ensure priority is restricted to those with the highest likelihood of favorable posttransplant outcome.     

Locoregional Therapy-Induced Tumor Necrosis as a Predictor of Recurrence after Liver Transplant in Patients with Hepatocellular Carcinoma

Background

Patients with hepatocellular carcinoma (HCC) often undergo locoregional therapy before liver transplant either to downstage the tumor or as bridge therapy. Our goal was to assess the risk factors for posttransplant tumor recurrence, specifically the extent of necrosis induced by locoregional therapy.

Methods

We conducted a hospital-based retrospective analysis of 100 patients with HCC who received a liver transplant, 86 of whom had received pretransplant locoregional therapy. We evaluated various patient- and tumor-related parameters to determine the risk factors for recurrence. Furthermore, we grouped patients by the degree of tumor necrosis after locoregional therapy and identified the factors that were associated with a favorable tumor response.

Results

Initial tumor extent beyond the University of San Francisco (UCSF) criteria, microvascular invasion, and attainment of less than 90% tumor necrosis after locoregional therapy were independent risk factors for tumor recurrence. In addition, there was a significant correlation between the tumor necrosis percentage and disease-specific survival rate. Among patients whose tumors initially exceeded the UCSF criteria, those with extensive locoregional therapy-induced tumor necrosis had lower recurrence rates. All recurrences after transplant occurred within 3 years, and recurrence rates in patients with extensive tumor necrosis at 1, 2, and 3 years were 3%, 6%, and 10%, respectively. Female gender and a solitary tumor were independently associated with extensive tumor necrosis.

Conclusions

In HCC patients who are transplant candidates and undergo pretransplant locoregional therapy, the degree of induced tumor necrosis affects both tumor recurrence and survival rate.     

Significance of Tumor Necrosis for Outcome of Patients with Hepatocellular Carcinoma Receiving Locoregional Therapy Prior to Liver Transplantation

Background

Locoregional therapy has been advocated as an effective treatment for patients with unresectable hepatocellular carcinoma (HCC), and the majority of patients with HCC receive locoregional therapy prior to liver transplantation (LT). We herein aim to determine the prognostic factors affecting the outcome in patients who receive pretransplantation therapy.

Methods

We conducted a retrospective study of the prospective data of patients who received locoregional therapy before undergoing LT for HCC. The clinicopathologic features of the patients were studied using univariate and multivariate analysis to determine prognostic factors.

Results

Univariate and multivariate analysis of clinicopathologic features identified mean tumor necrosis (TN) ≥60% as the sole independent factor associated with lower HCC recurrence following LT. Further, the groups of patients with mean TN ≥60% who were within the University of California, San Francisco (UCSF) criteria and whose tumors beyond UCSF criteria were downstaged by TN following locoregional therapy had significantly better survival rates than the opposite groups. In-depth exploration of treatment modalities and pathological features indicated that HCC showed marked TN, while tumor nodules were well treated by locoregional therapy, and no viable tumors could be detected on radiological examination.

Conclusions

Mean TN ≥60% of tumor by locoregional therapy could offer better outcomes for patients with HCC undergoing LT. Therefore, locoregional therapy should be considered for patients with HCC awaiting LT or potential candidates for LT in order to induce TN as well as leading to diminished viable tumor burden and reducing the odds of HCC recurrence following LT.

     

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.     

Outcome Comparisons Among the Hangzhou, Chengdu, and UCSF Criteria for Hepatocellular Carcinoma Liver Transplantation after Successful Downstaging Therapies

Background

In Mainland China, many selection criteria for hepatocellular carcinoma (HCC) liver transplantation, such as the Hangzhou, the Chengdu, and the Fudan criteria, have been established. No comparisons have been made among the outcomes using the Hangzhou, Chengdu, and University of California, San Francisco (UCSF) criteria in patients who underwent successful downstaging therapies.

Methods

After successful downstaging therapies, 72 patients met the UCSF criteria, 86 met the Chengdu criteria, and 102 met the Hangzhou criteria. The data on these HCC patients were retrospectively analyzed, and various outcomes, such as survival and the tumor-free survival rate, were compared among the three groups.

Results

No significant differences were observed among the three groups with regard to the downstaging protocols, baseline characteristics, or liver function. However, the patients who met the Hangzhou criteria had significantly larger tumor targets than those who met the Chengdu or UCSF criteria (P?<?0.05). The three groups showed similar 1-, 3-, and 5-year survival rates (90.9, 80.0, and 78.6 %, respectively, for the UCSF criteria; 91.6, 81.9, and 75.6 %, respectively, for the Hangzhou criteria; and 91.1, 83.3, and 79.4 %, respectively, for the Chengdu criteria); 1-, 3-, and 5-year tumor-free survival rates (83.3, 77.5, and 75 %, respectively, for the UCSF criteria; 86.3, 78.8, and 75.6 %, respectively, for the Hangzhou criteria; and 87.3, 79.2, and 76.4 %, respectively, for the Chengdu criteria); and 1-, 3-, and 5-year tumor recurrence rates (9.2, 17.5, and 21.4 %, respectively, for the UCSF criteria; 8.4, 16.4, and 20 % for the Hangzhou criteria; and 8.9, 14.6, and 17.6 % for the Chengdu criteria).

Conclusion

Because they have contributed to similar outcomes but to larger HCC patient pools, the Hangzhou criteria for HCC transplantation should be comprehensively accepted in China for HCC patients after successful downstaging therapies.     

Financial Burden of Liver Transplant vs Resection for Hepatocellular Carcinoma

BackgroundLiver transplant and liver resection are surgical treatments for hepatocellular carcinoma (HCC) performed with curative intent. While liver transplant provides longer survival when compared to resection, the financial burden on patients and payors is significantly greater. With the increase in health care costs and the emergence of high deductible insurance policies that increase out of pocket deductibles for patients, assessment of value-based treatment is warranted.MethodsWe compiled total billable events from diagnosis of HCC through resection (N = 20) or transplant (N = 24) to death or last reported encounter from January 2011 to December 2012.ResultsPatients with HCC receiving resection had a model of end stage liver disease of 10.2 ± 1.2, survival 652 days (3–1, 167 days), and billable encounters of $316,873 ($2904/day). HCC patients receiving a liver transplant had a greater liver injury (model of end stage liver disease of 19.2 ± 3.7), longer survival (1579 days), and higher billable encounters, $740,714 ($2889/day). The surgical procedure represented the largest cost category (28% and 26% resection vs transplant, respectively). The cost effectiveness of treatment was directly proportional to length of survival. In resection, patients who survived >30 days (85%) cost per day dropped to $432. Transplant patients who survived >2 years (75%) saw the cost per day drop to $462.ConclusionThe relative financial burdens of liver resection vs liver transplant for treating HCC are comparable in patients who survive beyond a certain threshold. Transplant patients survived longer, and survival beyond 2 years makes this approach cost effective. In a health care climate aiming to contain costs and evaluate value-based treatment paradigms, expected survival and financial burden should be included in the treatment decision analysis.     

Alpha-Fetoprotein as a Modifier of Anatomic Criteria for Transplantation of HCC Patients

BackgroundThe current listing criteria (Milan, University of California San Francisco [UCSF]) for orthotropic liver transplants (OLT) in hepatocellular carcinoma (HCC) patients emphasize the anatomic features of the tumor such as size, burden, and multiplicity. Recent reports showed that patients with large tumors may have equivalent survival to Milan criteria patients. This suggests that differences in biologic behavior of tumors may contribute to the outcome.AimThe aim of this article is to understand the impact of biologic modifiers such as alpha-fetoprotein (AFP) on survival in both Milan and UCSF HCC patients.MethodsWe reviewed all liver transplants reported to the United Network for Organ Sharing between 2002 and 2013. We analyzed the survival of patients transplanted for HCC who fit the Milan criteria and those transplanted with tumors beyond Milan and within UCSF criteria. We tested various AFP level cutoffs in both groups in relationship to the 1-, 3-, and 5-year survival rates below and above the proposed cutoffs.ResultsSurvival difference was significant between Milan patients with AFP ≤ 2500 ng/mL and those with AFP > 2500 ng/mL (59.1% vs 37.4%; P < .001). The mean 5-year survival was 55% for beyond Milan within UCSF patients with AFP ≤ 150 ng/mL and 35.7% for those with AFP > 150 ng/mL (P = .003).ConclusionAFP level should be incorporated in the selection criteria for HCC patients considered for OLT. Milan patients with an AFP level exceeding 2500 ng/mL have reduced survival. Patients with tumors beyond Milan and within UCSF criteria whose AFP ≤ 150 ng/mL achieve acceptable 5-year survival and are good candidates for OLT.     

A prospective study on downstaging of hepatocellular carcinoma prior to liver transplantation.

In patients with hepatocellular carcinoma (HCC) exceeding conventional (T2) criteria for orthotopic liver transplantation (OLT), the feasibility and outcome following loco-regional therapy intended for tumor downstaging to meet T2 criteria for OLT are unknown. In this first prospective study on downstaging of HCC prior to OLT, the eligibility criteria for enrollment into a downstaging protocol included 1 lesion >5 cm and < or =8 cm, 2 or 3 lesions at least 1 >3 cm but < or =5 cm with total tumor diameter of < or =8 cm, or 4 or 5 nodules all < or =3 cm with total tumor diameter < or =8 cm. Patients were eligible for living-donor liver transplantation (LDLT) if tumors were downstaged to within proposed University of California, San Francisco (UCSF) criteria.13 A minimum follow-up period of 3 months after downstaging was required before cadaveric OLT or LDLT, with imaging studies meeting criteria for successful downstaging. Among the 30 patients enrolled, 21 (70%) met criteria for successful downstaging, including 16 (53%) who had subsequently received OLT (2 with LDLT), and 9 patients (30%) were classified as treatment failures. In the explant of 16 patients who underwent OLT, 7 had complete tumor necrosis, 7 met T2 criteria, but 2 exceeded T2 criteria. No HCC recurrence was observed after a median follow-up of 16 months after OLT. The Kaplan-Meier intention-to-treat survival was 89.3 and 81.8% at 1 and 2 yr, respectively. In conclusion, successful tumor downstaging can be achieved in the majority of carefully selected patients, but longer follow-up is needed to further access the risk of HCC recurrence after OLT.     

Comparative evaluation of expanded criteria for patients with hepatocellular carcinoma beyond the Milan criteria undergoing living-related donor liver transplantation

Shirabe K, Taketomi A, Morita K, Soejima Y, Uchiyama H, Kayashima H, Ninomiya M, Toshima T, Maehara Y. Comparative evaluation of expanded criteria for patients with hepatocellular carcinoma beyond the Milan criteria undergoing living‐related donor liver transplantation.
Clin Transplant 2011: 25: E491–E498. © 2011 John Wiley & Sons A/S. Abstract: Objective: To clarify the predictive impact of expanded criteria for liver transplantation (LT) for patients with hepatocellular carcinoma (HCC) in 54 patients with HCC beyond the Milan criteria (MC) from a series of 109 consecutive living‐related donor liver transplantation (LDLT) recipients with HCC. Methods: Among 54 patients with HCC exceeding the MC, the predictive values for HCC recurrence within expanded criteria comprising the UCSF, Tokyo, Kyoto, Kyushu University (based on the tumor size and des‐gamma carboxy prothrombin level) and Up‐to‐seven criteria were compared using univariate and multivariate analyses. The histological characteristics of HCC were compared among these extended criteria. Results: All five criteria were significant predictors for recurrence‐free survival after univariate analyses. The Kyushu University criteria were the most powerful predictive criteria for HCC recurrence after multivariate analyses. The incidence of microvascular invasion and poorly differentiated HCC was significantly higher in patients with HCC exceeding the Kyushu University criteria than in those with HCC within the criteria. Conclusions: Compared with the other expanded criteria, the Kyushu University criteria may be useful to eliminate LT candidates at very high risk of HCC recurrence. The Kyushu University criteria were useful to evaluate LT candidates with HCC.     

Predictors of Outcome of Living Donor Liver Transplantation for Hepatocellular Carcinoma

The aim of this work is to study the different factors that affect the outcome of living donor liver transplantation for patients with hepatocellular carcinoma (HCC). Between April 2003 to November 2014, 62 patients with liver cirrhosis and HCC underwent living donor liver transplantation (LDLT) in the National Liver Institute, Menoufia University, Egypt. The preoperative, operative, and postoperative data were analyzed. After studying the pathology of explanted liver; 44 (71 %) patients were within the Milan criteria, and 18 (29 %) patients were beyond Milan; 13 (21.7 %) of patients beyond the Milan criteria were also beyond the University of California San Francisco criteria (UCSF) criteria. Preoperative ablative therapy for HCC was done in 22 patients (35.5 %), four patients had complete ablation with no residual tumor tissues. Microvascular invasion was present in ten patients (16 %) in histopathological study. Seven (11.3 %) patients had recurrent HCC post transplantation. The 1, 3, 5 years total survival was 88.7, 77.9, 67.2 %, respectively, while the tumor-free survival was 87.3, 82.5, 77.6 %, respectively. Expansion of selection criteria beyond Milan and UCSF had no increased risk effect on recurrence of HCC but had less survival rate than patients within the Milan criteria. Microvascular invasion was an independent risk factor for tumor recurrence.     

Number and Tumor Size Are Not Sufficient Criteria to Select Patients for Liver Transplantation for Hepatocellular Carcinoma

Background

Hepatocellular carcinoma (HCC) is an indication for liver resection or transplantation (LT). In most centers, patients whose HCC meets the Milan criteria are considered for LT. The first objective of this study was to analyze whether there is a correlation between the pathologic characteristics of the tumor, survival and recurrence rate. Second, we focused our attention on vascular invasion (VI).

Methods

From January 1997 to December 2007, a total of 196 patients who had a preoperative diagnosis of HCC were included. The selection criteria for LT satisfied both the Milan and the San Francisco criteria (UCSF). Demographic, clinical, and pathologic information were recorded.

Results

HCC was confirmed in 168 patients (85.7%). The median follow-up was 74?months. The pathologic findings showed that 106 patients (54.1%) satisfied the Milan criteria, 134 (68.4%) the UCSF criteria of whom 28 (14.3%) were beyond the Milan criteria but within the UCSF criteria, and 34 (17.3%) beyond the UCSF criteria. VI was detected in 41 patients (24%). The 1-, 3-, and 5-year overall survival rates were 90%, 85%, and 77%, respectively, according to the Milan criteria and 90%, 83%, and 76%, respectively, according to the UCSF criteria (P?=?NS). In univariate and multivariate analyses, tumor size and VI were significant prognostic factors affecting survival (P?400?ng/ml and tumor grade G3.

Conclusions

Tumor size and VI were the only significant prognostic factors affecting survival of HCC patients. Primary liver resection could be a potential selection treatment before LT.     

A single‐center retrospective analysis of liver transplantation on 255 patients with hepatocellular carcinoma

Wang Z‐X, Song S‐H, Teng F, Wang G‐H, Guo W‐Y, Shi X‐M, Ma J, Wu Y‐M, Ding G‐S, Fu Z‐R. A single‐center retrospective analysis of liver transplantation on 255 patients with hepatocellular carcinoma.
Clin Transplant 2010: 24: 752–757. © 2009 John Wiley & Sons A/S. Abstract: Background: Liver transplantation (LT) was advocated as a salvage treatment of choice for patients with unresectable hepatocellular carcinoma (HCC). This study was designed to assess the eligibility of LT criteria for patients with HCC and to analyze the factors influencing the recurrence of HCC following LT, aiming to further improve the efficacy of LT for patients with HCC. Methods: Clinical data of 255 patients with HCC who underwent LT between December 2001 and December 2007 at Shanghai Changzheng Hospital, China were retrospectively analyzed. Results: Among these cases, 75 patients were within the Milan criteria and 180 were beyond it; 110 patients were within the University of California, San Francisco (UCSF) criteria, while 145 were beyond it. The difference in overall survival rates was not only significant between the patients within and beyond the Milan criteria but also between patients within and beyond the UCSF criteria. Tumor‐node‐metastasis (TNM) staging, portal vein tumor thrombus (PVTT), and the pre‐operative alpha‐fetoprotein (AFP) level were independent risk factors affecting the overall survival and post‐operative recurrence‐free survival rates of patients with HCC. Pathological staging and pre‐operative local treatment of HCC had no obvious correlation with the post‐operative recurrence‐free survival rate. Conclusion: LT is an effective treatment modality for HCC. The UCSF criteria did not show better effectiveness than the Milan criteria. TNM staging, PVTT, and the pre‐operative AFP level are closely related to the recurrence of HCC following LT.     

Liver Transplantation for Hepatitis B Virus-Related Hepatocellular Carcinoma: One Center's Experience in China

Background

Hepatocellular carcinoma (HCC) is the fifth most common and the third most deadly cancer worldwide, with more than half a million identified cases and about a similar number of subjects succumb to it each year. This study sought to evaluate our results of liver transplantation for HCC to identify prognostic factors.

Methods

Between December 2001 and December 2006, 224 patients (205 men, 19 women; age range, 15-75 years) with HCC underwent orthotopic liver transplantation (OLT) at our center. All grafts were from deceased donors. There were 68 cases within Milan criteria (30.3%), 32 cases beyond Milan criteria but within UCSF (University of California, San Francisco) criteria (14.3%), and 124 cases beyond UCSF criteria (55.4%).

Results

The overall 1-, 3-, and 5-year patient cumulative survival rates were 82.5%, 60.1%, and 51.5%, respectively. The survival rates were comparable between patients within Milan and UCSF criteria, but were significantly greater than that of patients beyond UCSF criteria. Multivariate analysis revealed alpha fetoprotein (AFP) ≥ 800 μg/L, vascular invasion, and poor tumor differentiation to be independent prognostic factors.

Conclusion

OLT is a safe and effective treatment for hepatitis B virus-related HCC. Compared with Milan criteria, UCSF criteria successfully expanded the indication without deteriorating the prognosis significantly, while preoperative AFP ≥ 800 μg/L, vascular invasion, and poor tumor differentiation indicated poor survival.     

肝癌肝移植的标准及其与预后的关系

目的 评价肝移植治疗肝细胞癌的价值以及受者选择对病人术后存活的影响.方法 对我院2000年6月至2007年2月实施的63例原发性肝细胞癌肝移植临床资料进行回顾性分析.采用kaplan-meier法进行生存率统计分析.结果 63例原发性肝细胞癌病人肝移植术后1、3、5年累积生存率分别为77.4%、59.3%、48.9%.符合Milan标准、符合UCSF标准和不符合UCSF标准受者,肝移植术后1、3、5年累积生存率分别为93.8%、92.1%、29.2%;80.8%、79.2%、8.3%;80.8%、79.2%、0.符合Milan标准、符合UCSF标准和不符合UCSF标准受者,术后1、2、3年肿瘤累积复发率分别为6.2%、15.5%、19.2%;7.9%、15.9%、20.8%;70.8%、87.5%、91.7%(P＜0.01).但是,符合UCSF标准与符合Milan标准受者移植术后累积生存率和肝癌累积复发率相似(P＞0.05).结论 以UCSF标准筛选肝癌病人进行肝移植不仅扩大了肝癌肝移植的适应证,还可以取得与Milan标准同样的效果.     

Analysis of the Risk Factors of Untransplantable Recurrence After Primary Curative Resection for Patients with Hepatocellular Carcinoma

Purpose

To determine the prognostic factors that predict recurrence of hepatocellular carcinoma (HCC) exceeding the University of California at San Francisco (UCSF) criteria after primary resection.

Methods

HCC patients who underwent curative liver resections between 2001 and 2007 and who were within the UCSF criteria (n = 716) were examined. Independent prognostic factors were examined by the Cox proportional hazard model.

Results

A total of 285 patients (39.8 %) developed recurrences. Of the patients who developed recurrences, 180 had HCC still within the UCSF criteria (63.2 %), and 105 developed HCC beyond this criteria (36.8 %). Among the population with primary transplantable HCC, patients with larger primary tumor sizes, serum α-fetoprotein (AFP) levels over 400 ng/mL, satellite nodules, vascular invasion, or undifferentiated HCC had a risk of untransplantable recurrence, as shown by univariate analysis. In multivariate analysis, undifferentiated HCC and vascular invasion were identified as the significant predictors with adjusted hazard ratios of 9.25 [95 % confidence interval (CI) 2.13–40.21] and 2.19 (95 % CI 1.34–3.58), respectively. When only preoperative factors were considered in multivariate analysis, primary tumor size and serum AFP levels over 400 ng/mL were identified as significant predictors with adjusted hazard ratios of 1.24 (95 % CI 1.07–1.45) and 1.72 (95 % CI 1.05–2.82), respectively.

Conclusions

For primary HCC patients within the UCSF criteria, larger tumor sizes and AFP levels over 400 ng/mL were associated with postresection recurrence of HCC exceeding the UCSF criteria. Because these are clearly markers for aggressive tumor biology, whether early primary transplant will alter the aggressive tumor behaviors warrant further investigation.     

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目的分析超出加利福尼亚大学(UCSF)标准肝癌肝移植病人的生存情况,探讨影响预后的因素。方法对2006年1月至2010年12月间中山大学附属第一医院超过UCSF标准的肝癌肝移植病人的临床病历资料进行回顾性分析,应用Kaplan-Meier法计算病人存活率,应用Log-Rank检验进行单因素分析,应用Cox比例风险模型进行多因素分析,探讨临床和肿瘤病理因素与病人存活率之间的关系。结果单因素分析显示对存活率和(或)无瘤存活率有影响的有:肿瘤Edmondson分级、肿瘤TNM分期和肿瘤门静脉侵犯、术前AFP水平、术前淋巴结转移(P<0.05);Cox回归分析显示,肿瘤Edmondson分级Ⅲ-Ⅳ级和肿瘤门静脉侵犯(P<0.05)是与预后相关的独立因素。结论对于超出UCSF标准的肝癌病人,移植的总体效果是欠佳的,但也有部分病人可获得较长期的存活或带瘤生存,肿瘤Edmondson分级和门静脉侵犯是影响该组病人预后的重要因素。     

肝移植治疗原发性肝癌103例疗效观察

目的 比较不同受体选择标准肝癌肝移植的远期疗效,分析肝痛肝移植术后肿瘤复发相关因素.方法 总结北京佑安医院2004年4月至2008年3月间的103例肝癌肝移植的临床资料,按照肿瘤的特征将其分为3组:符合米兰标准组(A组)、超出米兰标准但满足UCSF标准组(B组)和超出UCSF标准组(C组),比较3组的总体生存率及无瘤生存率,并分析影响远期预后的相关因素.结果 103例肝癌肝移植总体1、2、3年存活率分别为84.0%、70.5%和60.2%.其中A组50例,1、2、3年生存率和无瘤生存率分别为93.4%、83.8%、73.2%和97.3%、93.9%、88.7%;B组17例,1、2、3年生存率和无瘤生存率分别为93.3%、79.4%、66.2%和86.7%、79.4%、66.2%;C组36例,1、2、3年生存率和无瘤牛存率分别为67.0%、45.5%、34.1%和65.8%、50.0%、41.7%.远期生存率A组与B组比较无差异(P=0.631),A组、B组与C组比较具有统计学差异(P值分别为0.001,0.045).结论 米兰标准是肝癌肝移植最佳适应证,超出米兰标准但满足UCSF标准也可获得满意的远期疗效;肿瘤的分期和微血管侵犯是影响远期预后的风险因素.     

Hepatocellular carcinoma downstaging in liver transplantation

Background

Hepatocellular carcinoma (HCC) is the leading malignant tumor in Taiwan. The majority of HCC patients are diagnosed in late stages and therefore in eligible for potentially curative treatments. Locoregional therapy has been advocated as an effective treatment for patients with advanced HCCs.

Purpose

The aim of this study was to evaluate the outcomes of HCC downstaged patients after locoregional therapy to allow eligibility for liver transplantation.

Methods and materials

From January 2004 to June 2010, 161 patients with HCCs underwent liver transplantation including 51 (31.6%) who exceeded the University of California-San Francisco (UCSF) who had undergone successful locoregional therapy to be downstaged within these criteria. Among the downstaged patients, 48 (94.1%) underwent transarterial embolization; 7 (13.8%), percutaneous ethanol injection; 24 (47.1%), radiofrequency ablation; 15 (29.4%), surgical resection, and 34 (66.7%), combined treatment.

Results

The overall 1- and 5-year survival rates of all HCC patients (n = 161) were 93.2% and 80.5%. The overall 1- and 5-year survival rates of downstaged (n = 51) versus non-downstaged (n = 110) subjects were 94.1% versus 83.7% and 92.7% versus 78.9%, respectively (P = .727). There are 15 (9.2%) HCC recurrences. The overall 1- and 5-year tumor-free rates of all HCC patients were 94.8% and 87.2%. The overall 1- and 5-year tumor-free rates between downstaged versus non-downstaged patients were 93.9% and 90.1% versus 95.2% and 86.0%, respectively (P = .812).

Conclusion

Patients with advanced HCC exceeding the UCSF/Milan criteria can be downstaged to fit the criteria using locoregional therapy. Importantly, successfully downstaged patients who are transplanted show excellent tumor-free and overall survival rates, similar to fit-criteria group.     

Rate of tumor growth predicts recurrence of hepatocellular carcinoma after liver transplantation in patients beyond Milan or UCSF criteria

Background

It is likely that some patients whose tumor burdens exceed the current transplant criteria have favorable tumor biology, and that these patients would have low risk of tumor recurrence after liver transplantation (LT). To assess the rate of tumor growth as selection criteria for LT in patients with hepatocellular carcinoma (HCC).

Methods

We identified all patients who underwent LT for HCC in our institution from 2002 to 2008. Total tumor volume (TTV) was calculated as the sum of the volumes of all tumors on pretransplantation imaging [(4/3)πr³, where r is the maximum radius of each HCC]. The rate of tumor growth was calculated as per-month change in TTV on sequential pretransplantation imaging before any locoregional therapy. A Kaplan-Meier plot was constructed and Cox regression analysis performed.

Results

Ninety-two patients were included in the study. The median follow-up was 19.5 (range 10.7–30.7) months during which 12 patients (13%) experienced recurrence of HCC. Twenty-four patients (26%) had HCC beyond the Milan criteria, and the overall survival rate of the entire group was 72%. Higher pre-LT alpha-fetoprotein (hazard ratio [HR] 1.01; P = .001), poorly differentiated tumors (HR 13; P = .039), the presence of microvascular invasion (HR 7.9; P = .001), higher TTV (HR 1.03; P < .001), and faster tumor growth (HR 1.09; P < .001) were significantly associated with the risk of recurrence. A cutoff value of tumor growth of 1.61 cm³/mo was chosen on the basis of the risk of recurrence with the use of a receiver operating characteristic curve. Patients beyond the Milan criteria with tumor growth <1.61 cm³/mo experienced less recurrence (11% vs 58%; P = .023) than those beyond the Milan criteria with tumor growth >1.61 cm³/mo. Similarly, rate of tumor growth predicted HCC recurrence in those beyond the University of California of San Francisco (UCSF) criteria.

Conclusions

Patients with slowly growing tumor who would be currently excluded from LT because tumor burden exceeds traditional Milan and UCSF criteria may have a favorable posttransplantation outcome.     

Liver transplantation for hepatocellular carcinoma: Comparison of the proposed UCSF criteria with the Milan criteria and the Pittsburgh modified TNM criteria

We previously proposed modified staging criteria for predicting acceptable outcome after orthotopic liver transplantation (OLT) for hepatocellular carcinoma (HCC). These were solitary tumor ≤6.5 cm, or three or fewer nodules with the largest lesion ≤4.5 cm and total tumor diameter ≤8 cm, without gross vascular invasion (University of California, San Francisco [UCSF] criteria). In this study, we further evaluated the performance of the Milan criteria (solitary tumor ≤5 cm, or three or fewer lesions none >3 cm), the UCSF criteria, and the Pittsburgh modified tumor-node-metastasis (TNM) criteria. Pathologic HCC staging according to each set of criteria was performed in 70 patients. The difference in survival when comparing 24 patients with HCC exceeding Milan criteria versus 46 patients meeting Milan criteria did not reach statistical significance (HR, 2.0; P = .12). Using our definition for acceptable 2-year survival to be ≥70%, the 14 patients (20%) meeting UCSF criteria but exceeding Milan criteria had a 2-year survival of 86% (95% CI, 54% to 96%). Survival for Pittsburgh stage I, II, and IIIA patients as a group was significantly better than for stages IIIB and IVA patients combined (HR, 4.2; P = .007), and similar to survival for patients meeting UCSF criteria. Advanced tumor exceeding UCSF criteria served reasonably well as a surrogate marker for poorly differentiated grade and microvascular invasion. In conclusion, our analyses suggest that UCSF criteria better predict acceptable posttransplant outcome than Milan criteria. UCSF criteria confer a different advantage over Pittsburgh criteria, which require information on microvascular invasion that is difficult to ascertain preoperatively without the attendant risk of biopsy. (Liver Transpl 2002;8:765-774.)