Expanded criteria for hepatocellular carcinoma and liver transplantation

In this study, we evaluated our early results of liver transplantation for hepatocellular carcinoma (HCC). Between January 2004 and June 2006, 26 patients (4 females, 22 males; aged 1.1-65 years) with preoperatively diagnosed or incidental HCC underwent liver transplantation at our center. Inclusion criteria (independent of tumor size and number of tumor nodules) were no invasion of major vascular structures and no evidence of extrahepatic disease. In 13 of the patients, tumors were beyond the Milan criteria. At this writing, at a mean follow-up of 16.5 months (range, 1-31 months), all patients were doing well with excellent graft function. The longest survival is 2.5 years, and our patient survival rate is 100%. There has been only 1 tumor recurrence, which occurred 4 months after liver transplantation. In conclusion, liver transplantation provides long patient and disease-free survival, even in patients with HCC that exceeds the Milan criteria.     

Living donor liver transplantation for hepatocellular carcinoma: a single-center preliminary report.

Liver transplantation (LT) is the treatment of choice for early hepatocellular carcinoma (HCC) in patients with end-stage liver disease but is limited by the availability of donor organs. Living donor liver transplantation (LDLT) represents an alternative therapeutic option for patients with disease confined to the liver. Between April 1998 and December 2003, 537 patients underwent liver transplantation in our center. Thirty patients with HCC and associated terminal cirrhosis and 4 patients with tumor recurrence after liver resection who underwent LDLT were reviewed. Nineteen patients (55.8%) met the Milan criteria for LT, whereas 15 patients (44.2%) "exceeded" them. The overall survival rates at 1 and 2 years were 68% and 62%, respectively, with a median follow-up of 41 months (range, 17-64 months). Five patients (14.7%) died in the first 30 days after LDLT. Hospital mortality was significantly correlated with age > 60 years. Four patients developed recurrence between 6 and 35 months after LDLT. Recurrence was significantly related to the presence of more than 3 tumor lesions in our series. In conclusion, LDLT is a promising treatment option for patients with HCC. Even longer follow-up and bigger patients' series are needed to fully assess the benefits of LDLT for HCC patients exceeding the Milan criteria.     

Liver transplantation for the treatment of moderately or well-differentiated hepatocellular carcinoma

OBJECTIVE: To determine the long-term results of liver transplantation for well- or moderately differentiated hepatocellular carcinoma (HCC). SUMMARY BACKGROUND DATA: HCC patient selection for liver transplantation remains controversial, and deciding exclusively on the strength of criteria such as number and size of nodules appears prognostically inaccurate. METHODS: Since 1991, preoperative tumor grading has been used at our center to establish whether a patient with HCC is fit for transplantation. Poorly differentiated HCC cases were excluded, while size and number of nodules were not considered as absolute selection criteria. Thirty-three patients with moderately or well-differentiated HCC were prospectively studied after liver transplantation. A group of 15 patients with incidental HCC transplanted during the same period were also evaluated and compared with the 33 patients with preoperatively diagnosed HCC. RESULTS: On histologic examination, 38% of the entire group of 48 patients did not meet the "Milan criteria" and 42% were pTNM stages III and IV. The median follow-up was 44 months. The 5-year actuarial survival rate was 75% and recurrence-free survival was 92%. HCC recurred in only 3 patients (6%). The only histomorphologic variable differing significantly between incidental and nonincidental HCC was nodule size. The timing of diagnosis (incidental vs. nonincidental HCC), the Milan criteria, and the TNM stage revealed no statistically significant impact on overall and recurrence-free survival rates. CONCLUSIONS: The routine pre-orthotopic liver transplantation tumor grading may represent a valid tool in the selection of unresectable HCC patients for transplantation.     

Comparison of clinical and pathological staging and long-term results of liver transplantation for hepatocellular carcinoma in a single transplant center

Liver transplantation (OLT) is a treatment for hepatocellular carcinoma (HCC) superimposed on cirrhosis provided that the disease meets defined criteria. The aim of the study was to evaluate our experience with respect to clinical and pathological staging and long-term results. From 1996 to 2005, 50 patients underwent OLT for HCC including 43 men (86%) and seven women (14%) of median age 57 years (range 37 to 67). All patients fulfilled the Milan criteria. The HCC diagnosis was based on preoperative imaging and alpha-fetoprotein levels; no tumor biopsy was performed. Upon histological examination of the resected specimens, we discovered 6 (12%) incidentalomas and 8 (16%) cases of no HCC. Finally we had 42 "true" HCC. Twenty-six patients (52%) have been downstaged and 10 (20%) upstaged by preoperative imaging; 15% were pT1, 45% were pT2, 27% pT3, and 13% pT4a. Twenty-six percent of cases exceeded the Milan criteria. One patient (pT4a) with microvascular invasion died of pulmonary metastases at 14 months after transplantation. No HCC recurrences within the liver have been encountered at a median follow-up of 20 months (range 0 to 80 months). Overall the estimated 1-, 3-, and 5-year survival rates were 83%, 77%, and 72%, respectively. One-, 3-, and 5-year estimated survival rates were 87%, 75%, and 75% for pT1, and pT2, and 75%, 67%, and 67% for pT3 and pT4a, respectively (P = .99). Based on our experience OLT for HCC has long-term results comparable to those without HCC despite the presence of a significant number of cases exceeding the Milan criteria upon pathological staging.     

Sirolimus-based immunosuppression for liver transplantation in the presence of extended criteria for hepatocellular carcinoma.

An increasing number of patients with hepatocellular carcinoma (HCC) are undergoing evaluation for listing for liver transplantation. Criteria for selection require ongoing review for suitability. A consecutive series of 40 patients with HCC within the standard Milan criteria (single tumors n = 19 < 5 cm, or up to 3 tumors < 3 cm) and beyond (Extended Criteria; single tumors n = 21 < 7.5 cm, multiple tumors < 5 cm) underwent liver transplant with a sirolimus-based immunosuppressive protocol designed to minimize exposure to calcineurin inhibitors and steroids. At 44.3 +/- 19.3 months (mean +/- standard deviation) follow-up, 1- and 4-year survivals (Kaplan-Meier) are 94.1 +/- 5.7% and 87.4 +/- 9.3%, in the Milan group, respectively, and 90.5 +/- 6.4% and 82.9 +/- 9.3% in the Extended Criteria group, respectively. Five patients died during follow-up, only 1 from recurrent HCC. Five tumor recurrences have occurred at median 17 (mean 22 +/- 17) months posttransplant, 1 in the Milan group and 4 in the Extended Criteria group. Median survival in the patients with recurrent tumor is 42 months (mean 45 +/- 25), and the median postrecurrence survival is 15.5 months (mean 23 +/- 16). The rate of patients who were alive and free of tumor at 1 and 4 years is 94.1 +/- 5.7% and 81.1 +/- 9.9%, respectively, in the Milan group and is 90.5 +/- 6.4% and 76.8 +/- 10.5%, respectively, in the Extended Criteria group. Five patients had sirolimus discontinued for toxicity, while 24 of 35 surviving patients have sirolimus monotherapy immunosuppression. In conclusion, the Milan criteria for liver transplantation in the presence of HCC can be carefully extended without compromising outcomes. This sirolimus based immunosuppression protocol appears to have beneficial effects on tumor recurrence and survival with an acceptable rate of rejection and toxicity.     

Living donor liver transplantation for hepatocellular carcinoma: a single-center experience in Taiwan

BACKGROUND: Living donor liver transplantation (LDLT) demonstrates certain survival benefits over deceased donor liver transplantation for hepatocellular carcinoma (HCC) but there is no consensus on criteria for the use of LDLT for HCC for hepatocellular carcinoma (HCC) taking into account strategies to improve survival. METHODS: Thirty-five patients (89% men) underwent LDLT for HCC. The mean age was 51 years (range, 22-61). The median disease severity scores were B, 11-20, and 2B for Child-Turcotte-Pugh, Model for End-stage Liver Disease, and United Network for Organ Sharing, respectively. The transplant records were retrospectively analyzed. RESULTS: All were within Milan criteria at time of transplantation. A novel approach to downstaging tumors initially beyond the Milan criteria was evaluated using transarterial embolization or percutaneous ethanol injection. Our initial results were encouraging as recipients whose tumors had been downstaged had not had recurrence to date. Seven (20%) patients underwent hepatectomy for HCC before undergoing transplant. The overall mean posttransplant follow-up in this series was 40.3 months (range, 23-75). The overall posttransplant complication rate requiring intervention was 11%. There was only one malignancy recurrence for an overall recurrence rate of 3%. Vascular invasion and small- for-size transplants did not seem to influence tumor recurrence. The nonestimated recipient 1-year, 3-year, and 5-year survivals were 98%, 96%, and 90%, respectively. CONCLUSION: This review emphasizes the need for early disease recognition and prompt intervention when Milan criteria are met to improve survival from HCC after LDLT.     

Liver transplantation for patients with hepatocellular carcinoma

BACKGROUND: Liver transplantation (LT) has been advocated as a salvage treatment for unresectable hepatocellular carcinoma (HCC). Selection criteria still need to be developed in Taiwan. OBJECTIVES: The purpose of our study was to assess the clinical findings and outcome of cirrhotic patients with HCC undergoing liver transplantation. METHODS: Our study consisted of 13 HCC patients who underwent liver transplantation during October 1996 to March 2003. The medical records and pathologic reports were analyzed retrospectively. RESULTS: Overall survival rates at 1 and 3 years were 86% and 61%, respectively. HCC recurrences occurred in three patients, one of whom is still alive with HCC recurrence 2 years after LT. The other two patients died of HCC recurrence 1 and 2 years after LT, respectively. Pretransplant alpha-fetoprotein (AFP) levels of >200 ng/mL were noted in all three patients with HCC recurrence. In contrast, only one of the ten patients without HCC recurrence had pretransplant AFP >200 ng/mL (P = .003). Four patients did not meet Milan criteria, two of whom had HCC recurrence. However, the other two patients with microscopic vascular invasion survived and were free of HCC. The only one patient, who had histologic grade 4 HCC, died of recurrence, although his tumor was AJCC stage 1. CONCLUSIONS: High AFP level is a risk factor for HCC recurrence after LT. In addition to Milan criteria, histologic tumor grading should be considered in patient selection. Microscopic vascular invasion may not affect the outcome of the patients with early HCC.     

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.     

Intention-to-Treat Analysis of Liver Transplantation in Selected, Aggressively Treated HCC Patients Exceeding the Milan Criteria

This prospective study analyzed the dropout probability and intention-to-treat survival rates of patients with hepatocellular carcinoma (HCC) selected and treated according to our policy before liver transplantation (LT), with particular attention to those exceeding the Milan criteria. Exclusion criteria for LT were macroscopic vascular invasion, metastases, and poorly differentiated disease at percutaneous biopsy. A specific multi-modal adjuvant algorithm was used to treat HCC before LT. A total of 100 HCC patients were listed for LT: 40 exceeded the Milan criteria in terms of nodule size and number (MILAN OUT) either at listing or in list, while 60 patients continued to meet the criteria (MILAN IN). The Milan criteria did not prove to be a significant predictor of dropout probability or survival rates using Cox's analysis. Cumulative dropout probability at 6 and 12 months was 0% and 4% for MILAN OUT, and 6% and 11% for MILAN IN. The intention-to-treat survival rates at 1 and 3 years were 95% and 85% in MILAN OUT, and 84% and 69% in MILAN IN. None of the 68 transplanted patients had recurrent HCC after a median 16-month follow-up (0-69 months). In conclusion, LT may be effective for selected, aggressively-treated HCC patients exceeding the Milan criteria.     

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.     

Living donor liver transplantation for hepatocellular carcinoma

Background

Liver transplantation is a widely accepted modality in the treatment of hepatocellular carcinoma (HCC). In our center, patients with HCC limited to the liver without macrovascular invasion are accepted as candidates for living donor liver transplantation (LDLT). The aim of this study was to describe the patient characteristics and outcomes at a single institution to analyze the impact of our criteria on the survival of HCC patients.

Patients and Methods

We reviewed the medical records of all HCC (n = 105) patients who underwent liver transplantation in our institution. We excluded deaths in the early postoperative period and deceased donor liver transplantation (DDLT) patients, leaving 74 subjects (65 males and 9 female). Their median age was 53 years (range, 19-69). Univariate Kaplan-Meier and multivariate Cox proportional hazards models were used to analyze overall and disease-free survivals.

Results

Thirty-two (43%) patients were within the Milan criteria, and 42 (57%) exceeded them. One- and 2-year overall survival rates for patients within versus exceeding the Milan criteria were 72% versus 68% and 61% versus 58%, respectively. One- and 2-year disease-free survival rates for patients within versus exceeding the Milan criteria were 72% versus 68% and 60% versus 55%, respectively (P > .05). Tumor recurrence rates for patients within versus exceeding the Milan criteria were 0% versus 36%, respectively (P = .0002). Alpha-fetoprotein level was the only predictor of overall survival; alpha-fetoprotein level and tumor differentiation were predictors of disease-free survival.

Conclusion

Although higher recurrence rates have been observed among patients exceeding the Milan criteria, LDLT is the only treatment option for the patients in countries with limited sources of cadaveric organs. As a general principle, we believe that the use of cadaveric donor liver grafts is not suitable for patients who exceed these criteria.     

超出Milan标准肝癌肝移植患者术后预防性化疗的价值

目的 探讨超出Milan标准肝癌肝移植患者术后预防性化疗的价值.方法 回顾性分析2001年4月至2007年7月243例超出Milan标准肝癌肌移植患者的临床资料,其中预防性化疗162例,未化疗81例.结果 预防性化疗与未化疗患者术后1、3年生存率(78.5%、63.7%和56.6%、39.1%)以及无瘤生存率(76.8%、52.5%和69.3%、64.7%)比较差异无统计学意义(X2=3.084,0.444,P>0.05).Cox风险比例分析显示,对无大血管侵犯的肝癌肝移植患者,术后足否化疗不是影响生存率的独立因素;对有大血管侵犯的肝癌肝移植患者,术后是否化疗是影响生存率的独立因素.结论 对于超出Milan标准且伴有大血管侵犯的肝癌肝移植患者,术后早期预防性化疗可以延缓肿瘤复发,明显提高疗效.     

肝癌肝移植术后雷帕霉素与普乐可复为主免疫抑制治疗结果初探

目的 探讨肝癌肝移植手术后使用雷帕霉素(rapamycin,RPM)与普乐可复为主的免疫抑制治疗是否有助于防止肝癌的复发与转移.方法 2004年1月至2005年1月期间19例肝癌行肝移植病人(米兰标准6例,扩大米兰标准13例)随机选取其中10位病人作为治疗组(米兰标准2例,扩大米兰标准8例)手术后使用雷帕霉素与普乐可复为主免疫抑制治疗,9例(米兰标准1例,扩大米兰标准8例),采用普乐可复为主的肝癌肝移植病人作为对照组,比较两组肝癌病人的累计生存率和累计无瘤生存率,并长期随访了解其复发转移情况.结果 肝癌病人肝移植术后生存时间及复发转移情况:至该文报告时,治疗组无死亡病例,仍存活1O例,其中无瘤生存9例,带瘤生存1例;对照组死亡1例,仍存活8例,其中无瘤生存5例,带瘤生存3例.两组经检验差异有显著性.结论 雷帕霉素可能有助于预防肝癌肝脏移植术后的转移与复发.     

Survival after liver transplantation for hepatocellular carcinoma

BACKGROUND: Selection criteria for patients with hepatocellular carcinoma (HCC) suitable for liver transplantation (LT) include tumor size and number and vascular invasion. There has been a recent trend to expand the transplant criteria for HCC. We reviewed our experience to determine survival following LT based on tumor characteristics. METHODS: A retrospective analysis was performed on 72 patients with HCC who underwent LT between 1985 and July 2002. The Milan criteria were applied for LT candidacy for HCCs that were deemed unresectable from anatomical considerations and/or the severity of underlying cirrhosis. Patients were divided into four groups: group 1: patients with known HCC who satisfied the selection criteria (n = 22); group 2: patients with known HCC that exceeded the criteria (n = 17); group 3: patients with incidental HCC found at pathological examination of the explant (n = 33); group 4: contemporary LT recipients without HCC (n = 935). RESULTS: In the known HCC group, the interval between listing as status 2 and transplantation was 72.2 +/- 133.6 days (median 23 days). Three-year patient survival was 80.2% in group 1, 35.8% in group 2, 63.2% in group 3, and 81.5% in group 4. In group 2 patients, the tumors were significantly larger, had more nodules, and were more often bilobar. In group 3, five (15%) exceeded the criteria mainly because of tumor size and four patients died within 3 years post-LT (three from tumor recurrence). CONCLUSION: Liver transplantation for HCC yields acceptable survival in early-stage tumors, particularly if transplanted soon after listing. Long-term survival was inferior in patients with multiple tumors and tumors that were greater than 5 cm in diameter.     

A Novel Model Measuring the Harm of Transplanting Hepatocellular Carcinoma Exceeding Milan Criteria

No empirical studies have defined the posttransplant survival that would justify expansion of the Milan criteria for liver transplantation of hepatocellular carcinoma. We created a Markov model comparing the survival benefit of transplantation for a patient with >Milan HCC, versus the harm caused to other patients on the waiting list.
In the base-case analysis, the strategy of transplanting the patient with >Milan HCC resulted in a 44% increased risk of death and a utility loss of 3 quality-adjusted years of life across the pre- and posttransplant periods for a nationally representative cohort of patients on the waiting list. This harm outweighed the benefit of transplantation for a patient with >Milan HCC having a 5-year posttransplant survival of less than 61%. This survival threshold was most sensitive to geographic variations in organ shortage, with the threshold varying from 25% (Region 3) to >72% (Regions 1, 5, 7 and 9).
In conclusion, expansion of the Milan criteria will require demonstrating high survival rates for the newly eligible patients—approximately 61% at 5 years after transplantation. In regions with less severe organ shortage, a more aggressive approach to transplanting these patients may be justified.     

Treatment of Hepatocellular Carcinoma With Liver Transplantation: A Single-Center Experience From Brazil

Introduction

Orthotopic liver transplantation (OLT) is the treatment of choice of hepatocellular carcinoma (HCC) for patients with cirrhosis, mainly those with early HCC. Herein we have present the clinical characteristics and outcomes of cirrhotic patients with HCC who underwent OLT from cadaveric donors in our institution.

Methods

From May 2001 to May 2009, we performed 121 OLT including 24 patients (19.8%) with cirrhosis and HCC within the Milan criteria. In 4 cases, HCC was an incidental finding in the explants.

Results

The patients' average age was 55 ± 10 years, including 82% men. Fifty percent of patients were Child class B or C. The average Model for End Stage Liver Disease for Child A, B, and C categories were 11, 15, and 18, respectively. The HCC diagnosis was made by 2 dynamic images in 16 cases; 1 dynamic image plus alphafetoprotein >400 ng/mL in 4; and 4 by histologic confirmation. Twenty patients received a locoregional treatment before OLT: 6 percutaneous ethanol injection, 9 transarterial chemoembolization, 1 transarterial embolization, and 4 a combination of these modalities. The median follow-up after OLT was 19.7 months (range, 1-51). A vascular invasion was observed in the explant of 1 patient, who developed an HCC recurrence and succumbed at 8 months after OLT. Two further patients, without vascular invasion or satellite tumor displayed tumor recurrences at 7 and 3 months after OLT, and death at 2 and 1 month after the diagnosis. The remaining 25 patients have not shown a tumor recurrence.

Conclusion

In the present evaluation, OLT patients with early HCC and no vascular invasion showed satisfactory results and good disease-free survival. Strictly following the Milan criteria for liver transplantation in patients with HCC greatly reduces but does not completely avoid, the chances of tumor recurrence.     

不同肝癌肝移植标准受者预后分析

目的分析不同肝癌肝移植标准受者预后情况,评价不同标准之间的差异。 方法回顾性分析2013年1月至2017年12月首都医科大学附属北京朝阳医院原发性肝癌肝移植受者的临床资料,比较不同肝癌肝移植标准受者的预后情况。采用单因素方差分析比较不同肝癌肝移植标准受者年龄、手术时间、无肝期时间和肿瘤最大直径,采用秩和检验比较AFP、终末期肝病模型评分和出血量。采用Kaplan-Meier法绘制生存曲线,采用Log-Rank检验比较生存率。采用卡方检验比较Child分级、肿瘤分化程度等指标。P<0.05为差异有统计学意义。 结果根据肝移植术后病理结果,115例肝癌肝移植受者中符合米兰标准43例;符合美国加州大学旧金山分校(UCSF)标准49例,较米兰标准扩大14.0%;符合杭州标准91例,较米兰标准扩大111.6%,较UCSF标准扩大85.7%。截至2017年12月,115例受者平均随访(19±17)个月,中位生存时间41.5个月(1.0～57.0个月)。除肿瘤最大直径和肿瘤数目外,3组不同肝癌肝移植标准受者均具有可比性(P均>0.05)。不同肝癌肝移植受者术后1～4年总体和和无瘤生存曲线差异均无统计学意义(P均>0.05)。 结论相较于米兰标准和UCSF标准而言,杭州标准安全地扩大了肝癌肝移植适用范围,使更多的原发性肝癌患者受益。     

Predictive factors of outcome after liver transplantation in patients with cirrhosis and hepatocellular carcinoma

Studies to define the optimal upper limits of tumor size and number as predictors of outcome after orthotopic liver transplantation (OLT) have yielded conflicting results. We analyzed 72 patients with cirrhosis and hepatocellular carcinoma (HCC) who underwent OLT over a 12-year period in a single center. Predictive factors for survival and tumor recurrence, according to the Milan criteria, were also examined. Our cohort included 60 men and 12 women of mean age 54 +/- 8 years and mean follow-up of 40 +/- 39 months. Origin of cirrhosis was postviral in 70% and Child class B or C in two thirds of patients. HCC was multifocal in 61%; about one fifth of patients had micro- or macrovascular involvement or positive nodes upon histologic examination. The cumulative size of the lesions was <3 cm in 17 patients; >3 to < or =5 cm in 28 patients; >5 to < or =8 cm in 14 patients; and >8 cm in 13 patients. According to the number and size of tumor nodules, 49 patients met the Milan criteria. During follow-up 25 patients died, 13 due to tumor recurrence. The 1- and 2-year survivals were 90% and 85% for patients who met the Milan criteria versus 57% and 51% for patients exceeding those limits (P = .006). A cumulative tumor size >8 cm was predictive of survival and tumor recurrence upon multivariate analysis. The adoption of Milan criteria for selection of cirrhotic patients has improved survival and reduced the rate of tumor recurrence. The evaluation of cumulative tumor size might further improve patient selection.     

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.     

Liver transplantation for hepatocellular carcinoma: University Hospital Essen experience and metaanalysis of prognostic factors

BACKGROUND: Liver transplantation has become one of the best treatment options for early hepatocellular carcinoma in cirrhosis. The purpose of this study was to correlate pathologic findings with outcomes after liver transplantation for hepatocellular carcinoma and to evaluate associations between various tumor characteristics and patient outcomes. STUDY DESIGN: One hundred patients with hepatocellular carcinoma underwent liver transplantation at our center during an 8-year period. Fifty-five patients received deceased donor livers and the remaining 45 received live donor grafts. A systematic literature search was performed. Using the truncated product method and Tippet's method p values from the literature were combined with our own results, for a total of 3,107 patients. RESULTS: For survival, significant associations were found for tumor grading in our series. Tumor recurrence was significantly associated with alpha-fetoprotein levels, tumor grading, vascular invasion, Milan and University of California San Francisco criteria in univariate analysis, and with tumor grading and University of California San Francisco criteria by multivariable analysis. Meta-analysis showed significant associations for all variables evaluated (alpha-fetoprotein, tumor number, tumor size, lobar distribution, vascular invasion, tumor differentiation, Milan criteria, and University of California San Francisco criteria) both for survival and recurrence in the performed univariate truncated product method analyses. Interestingly, metaanalysis of the available multivariable studies showed no significant associations between Milan/University of California San Francisco criteria and survival or tumor recurrence. CONCLUSIONS: Although results of this study add some corroborative evidence in this special field of transplantation for malignancy, they also open the discussion about the prognostic power of the current listing criteria.