Milan Criteria Versus San Francisco Criteria in Hepatocellular Carcinoma: Our Center's Experience

Background and aim

Liver transplantation (OLT) represents the best treatment for hepatocellular carcinoma (HCC) in advanced cirrhosis showing a 70% 5-year survival rate. Our study sought to compare overall survivals among patients who underwent OLT under Milan Criteria (MC) or San Francisco Criteria (UCSFC).

Methods

We retrospectively analyzed patients who underwent liver transplantation for HCC in our institution from November 2001 to December 2007. We analyzed age, gender, OLT indication, maximal tumor size, histology, and survival. We compared survival among patients who met MC versus UCSFC.

Results

From November 2001 to December 2007, 48/177 (27%) liver transplantations performed in our hospital were indicated due to HCC. The two patients who did not show any tumor in the explanted liver (false-positive ratio 4.2%) were excluded from the analysis. Another two patients were included who showed incidental HCC lesions (false-negative ratio 1.7%), yielding 48 analyzed patients. The mean diameter of the HCC nodules were 3.1 cm before OLT and 3.8 cm in the pathologic examination, a statistically significant difference. Two patients exceeded MC before OLT, and six patients showed this feature in the explanted liver. There was a significant difference in the degree of vascular invasion between the two groups. Overall mortality was 25.9% at 4 years; the MC group show an 11.9% versus UCSFC group, a 66.6% rate.

Conclusions

HCC is a common indication for OLT. Hepatitis C virus is the most common etiology. Survival among the MC group was significantly better than that of subjects beyond the MC, a difference that supports the use of MC for HCC.     

Effectiveness of locoregional therapy before living donor liver transplantation in patients with hepatocellular carcinoma who meet the Milan criteria

Background

Many patients are diagnosed with hepatocellular carcinoma (HCC) within the Milan criteria. In Korea, these patients are preferentially treated with locoregional therapy (LRT) instead of living donor liver transplantation. We investigated the effectiveness of LRT in liver transplant recipients who met the Milan criteria at the time of HCC diagnosis and investigated risk factors for HCC recurrence.

Methods

We retrospectively reviewed the medical records of patients diagnosed with HCC who met the Milan criteria between 2002 and 2008.

Results

We performed 101 liver transplants for HCC during the study period. Seventy-one patients (70%) underwent pretransplant LRT. The disease-free survival rates at 1, 3, and 5 years in patients who received LRT were 96.6%, 93.1%, and 93.1%, and in those who did not receive LRT, 94.2%, 83.4%, and 83.4%, respectively. There were no differences between the 2 groups. Multivariate analysis showed that a low Model for End-Stage Liver Disease (MELD) score and microvascular invasion were independent predictors of HCC recurrence after transplantation. The MELD scores and rate of microvascular invasion were not statistically different in patients with or without previous LRT.

Conclusion

Pretransplant LRT for patients with HCC who met the Milan criteria at the time of diagnosis did not provide a clear benefit with respect to HCC recurrence after transplantation. If patients have suitable living donors, those who meet the Milan criteria should undergo a liver transplantation as soon as possible.     

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.     

Living Donor Liver Transplantation for Hepatocellular Carcinoma: Long-Term Results Compared With Deceased Donor Liver Transplantation

Objective

Living donor liver transplantation (LDLT) may represent a valid therapeutic option allowing several advantages for patients affected by hepatocellular carcinoma (HCC) awaiting orthotopic liver transplantation (OLT). However, some reports in the literature have demonstrated worse long-term and disease-free survivals among patients treated by LDLT than deceased donor liver transplantation (DDLT) for HCC. Herein we have reported our long-term results comparing LDLT with DDLT for HCC.

Patients and Methods

Among 179 patients who underwent OLT from January 2000 to December 2007, 25 (13.9%) received LDLT with HCC 154 (86.1%) received DDLT. Patients were selected based on the Milan criteria. Transarterial chemoembolization, radiofrequency ablation, percutaneous alcoholization, or liver resection was applied as a downstaging procedure while on the waiting list. Patients with stage II HCC were proposed for LDLT.

Results

The overall 3- and 5-year survival rates were 77.3% and 68.7% versus 82.8% and 76.7% for LDLT and DDLT recipients, respectively, with no significant difference by the log-rank test. Moreover, the 3- and 5-year recurrence-free survival rates were 95.5% and 95.5% (LDLT) versus 90.5% and 89.4% (DDLT; P = NS).

Conclusions

LDLT guarantees the same long-term results as DDLT where there are analogous selection criteria for candidates. The Milan criteria remain a valid tool to select candidates for LDLT to achieve optimal long-term results.     

Salvage Liver Transplantation for Recurrent Hepatocellular Carcinoma After Liver Resection: Feasibility of the Milan Criteria and Operative Risk

Introduction

Although the Milan criteria are widely accepted for liver transplantation (OLT) for hepatocellular carcinoma (HCC), they have not been fully evaluated as feasible for salvage liver transplantation (SLT) of recurrent HCC after hepatic resection. The operative difficulties of SLT increase the operative risk. The aim of this study was to evaluate the feasibility of the Milan criteria for SLT and its operative complications.

Patients and methods

From March 2005 to November 2007, 46 HCC patients received OLT including 15 SLTs after prior partial hepatectomy (SLT group) and 31 primary OLTs (PLT group).

Results

There was no postsurgical hospital mortality among the SLT group but one case in the PLT group due to pneumonia followed by sepsis. There was no difference in the incidence of surgical complications between the two groups. Overall survival rates of SLT group patients were similar to those of the PLT group (P = .14), especially comparing both groups of patients within the Milan criteria (P = .89). There was no recurrence of HCC among the patients within the Milan criteria.

Conclusions

SLT is a feasible procedure for recurrent HCC meeting the Milan criteria; the operative risk of the SLT is also acceptable.     

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.     

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.     

Bridge Therapy in Hepatocellular Carcinoma Before Liver Transplantation: The Experience of Two Chilean Centers

Background

Orthotopic liver transplantation (OLT) is currently an established therapy for small, early-stage hepatocellular carcinoma (HCC) within the Milan criteria. Long waiting times due to the shortage of donor organs can result in tumor progression and drop-out from OLT candidacy. Therefore a wide variety of procedures are necessary before OLT. The aim of this retrospective study was to review our experience in relation to bridge therapy prior to OLT for HCC.

Methods

This was a retrospective database review of all of the patient who underwent transplantation in our institutions between January 1993 and June 2009. We analyzed patients with a diagnosis of HCC in the explant.

Results

Among 29 patients, including 12 who were diagnosed by the explant and 17 prior to transplantation, 88% underwent bridge therapy during a mean waiting time to OLT of 12 months. Among the 23 procedures, namely 1.5 procedures per patient, included most frequently chemoembolization (48%), alcohol ablation (30%), radiofrequency ablation (13%), and surgery (9%). Thirty-three percent of the explants contained lesions within the Milan criteria. In our series the 5-year survival rate for patients transplanted for HCC was 86%; in the bridge therapy group, it was 73%.

Conclusions

The incidence of patients who underwent bridge therapy (52%) was similar to other reported experiences, but the fulfillment of Milan criteria in the explants was lower. Among the bridge therapy group, the survival was slightly lower, probably because this group displayed more advanced disease.     

Orthotopic Liver Transplantation for Hepatocellular Carcinoma: A Thirteen-Year Single-Center Experience

Background

When restrictive selection criteria are applied orthotopic liver transplantation (OLT) is the most efficient option for the treatment of hepatocellular carcinoma (HCC) in terms of survival and recurrence rate. Nevertheless, tumor recurrence may occur in 3.5%-21% of recipients, with a consequent negative impact on prognosis. The aim of this study was to analyze the long-term survival and tumor recurrence rate among a cohort of liver transplant recipients with HCC.

Methods

During the period 1994-2007, 130 HCC patients, including 111 males with a mean overall age of 57.8 ± 7.1 years (range, 38-70), underwent cadaveric donor-OLT. The etiology of liver disease was alcoholic cirrhosis in 66 patients (50.8%) and viral infection in 52 patients (40%). Baseline alpha fetoprotein values were 53.4 ± 280.9 ng/mL (range, 1-2593). Median interval between inclusion date and transplantation was 179.5 days.

Results

After a median follow-up of 40.8 months, 93 recipients (71.5%) were alive. Tumor recurrence was detected in 11 patients (8.5%). Neoplasm recurrence sites were as follows: liver graft (45.4%), bone (36.4%), lymphoadenopathies (27.3%), adrenal glands (27.3%), and lung (27.3%). Overall survival rates at 1, 3, 5, and 10 years were 85.1%, 78.3%, 70.1%, and 57%, respectively. After examination of the explanted liver, Milan criteria were surpassed in 32 recipients (24.6%). Nevertheless, no differences in survival were observed according to fulfilment or not of Milan criteria (log-rank test, P > .05). Hepatitis C virus (HCV) infection, female gender, and tumor recurrence were associated with a worse survival rate (log-rank test, < .05).

Conclusions

OLT is an effective option for the treatment of HCC with good long-term survival and low recurrence rates. In this series, survival was not affected by findings of poor prognostic factors in the explanted liver.     

Sirolimus-Based Immunosuppression Therapy in Liver Transplantation for Patients With Hepatocellular Carcinoma Exceeding the Milan Criteria

Aim

Sirolimus (SRL) acts as a primary immunosuppressant or antitumor agent. The aim of the present study was to evaluate the influence of SRL on the recurrence rate and survival of patients after orthotopic liver transplantation (OLT) for hepatocellular carcinoma (HCC) exceeding the Milan criteria.

Materials and Methods

We retrospectively examined 73 consecutive patients who underwent OLT for HCC exceeding the Milan criteria from March 2004 through December 2005. Among them, 27 patients were treated with SRL-based immunosuppressive protocols after OLT, and 46 patients by an FK506-based protocol. Statistical analysis was based on the intent-to-treat method.

Results

The 2 groups were comparable in all clinicopathologic parameters. The mean overall survival was 594 ± 35 days in the SRL group and 480 ± 42 days in the FK506 group (P = .011); the mean disease-free survival period was 519 ± 43 days in the SRL group and 477 ± 48 days in the FK506 group (P = .234). Multivariate analysis revealed Child's status (P = .004) and immunosuppressive protocol (P = .015) were the significant factors affecting overall survival. Only microvascular invasion (P = .004) was significantly associated with disease-free survival. Among 24 surviving patient in the SRL group, 2 patients had SRL discontinued for toxicity; 10 had SRL monotherapy immunosuppression.

Conclusion

The SRL-based immunosuppressive protocol improved the overall survival of patients after OLT for HCC exceeding the Milan criteria, probably by postponing recurrence and with better tolerability.     

Liver Transplantation Results for Hepatocellular Carcinoma in Chile

Hepatocellular carcinoma (HCC) is the most common malignant tumor of the liver. Liver transplantation is the best treatment for HCC; it improves survival, cures cirrhosis, and abolishes local recurrence. We describe the outcomes of patients with HCC who underwent liver transplantation in two liver transplantation centers in Chile.

Methods

This study is a clinical series elaborated from the liver transplantation database of Pontificia Universidad Católica and Clínica Alemana between 1993 and 2009. The survival of patients was calculated using the Kaplan-Meier survival analysis. The significant alpha level was defined as <.05.

Results

From 250 liver transplantations performed in this period, 29 were due to HCC. At the end of the study, 25 patients (86%) were alive. The mean recurrence-free survival was 30 months (range 5 months to 8 years). The 5-year survival for patients transplanted for HCC was >80%; however, the 5-year overall survival of patients who exceeded the Milan criteria in the explants was 66%. There was no difference in overall survival between patients transplanted for HCC versus other diagnosis (P = .548).

Conclusion

This series confirmed that liver transplantation is a good treatment for patients with HCC within the Milan criteria.     

Progression of Hepatocellular Carcinoma Before Liver Transplantation: Dropout or Liver Transplantation?

Background

Tumor progression before liver transplantation (OLT) is the main cause of dropout from the waiting list (WL) of patients with hepatocellular carcinoma (HCC). The aim of this study was to show a correlation between adopted dropout criteria and dropout/intention-to-treat survival rates of WL HCC patients.

Methods

The study period was 2000 to 2007. The dropout criteria were macroscopic vascular invasion, metastases, or a poorly differentiated tumor. Adult patients with benign chronic liver disease enlisted for primary OLT in the same period represented the control group.

Results

Dropout probability of study (n = 128) versus control group (n = 377) subjects was similar: namely, 12% at 1 year in both groups (P = NS). Intention-to-treat survival curve of the HCC group overlapped that of the benign group (5-year survival rates were 73% and 71%, respectively; P = NS). At the time of listing, 103 study group patients were within the Milan criteria (MC): among these patients, 29 (28%) showed tumor progression beyond MC before OLT. Simulating the dropout of these 29 patients at the time of diagnosis of tumor progression, we compared the dropout probability of the 103 patients within MC with that of the control group. As a result, the 1- and 2-year dropout rates became 37% and 53%, respectively, in the study group, which were significantly higher than those in the controls (P < .01).

Conclusion

HCC patients on the WL showed a significantly greater dropout rate than subjects with benign cirrhosis when too restrictive radiologic dropout criteria were used. The adoption of criteria more related to biological aggressiveness of a tumor decreased the dropout risk for HCC patients without impairing their intention-to-treat survival rates.     

Late recurrence of hepatocellular carcinoma after liver transplantation: is an active surveillance for recurrence needed?

Introduction

Liver transplantation (OLT) is considered the most efficient therapeutic option for patients with liver cirrhosis and early stage hepatocellular carcinoma (HCC) in terms of overall survival and recurrence rates, when restrictive selection criteria are applied. Nevertheless, tumor recurrence may occur in 3.5% to 21% of recipients. It usually occurs within 2 years following OLT, having a major negative impact on prognosis. The efficacy of active posttransplantation surveillance for recurrence has not been demonstrated, due to the poor prognosis of recipients with recurrences.

Aim

To analyze the clinical, pathological, and prognostic consequences of late recurrence (>5 years after OLT).

Method

We analyzed the clinical records of 165 HCC patients including 142 males of overall mean age of 58 ± 6.9 years who underwent OLT between July 1994 and August 2011.

Results

Overall survival was 84%, 76%, 66.8%, and 57% at 1, 3, 5, and 10 years, respectively. Tumor recurrence, which was observed in 18 (10.9%) recipients, was a major predictive factor for survival: its rates were 72.2%, 53.3%, 26.7%, and 10% at 1, 3, 5, and 10 years, respectively. HCC recurrence was detected in 77.8% of patients within the first 3 years after OLT. Three recipients (100% males, aged 54-60 years) showed late recurrences after 7, 9, and 10 years. In only one case were Milan criteria surpassed after the examination of explanted liver; no vascular invasion was detected in any case. Recurrence sites were peritoneal, intrahepatic, and subcutaneous abdominal wall tissue. In all cases, immunosuppression was switched from a calcineurin-inhibitor to a mammalian target of rapamycin inhibitor. We surgically resected the extrahepatic recurrences. The remaining recipient was treated with transarterial chemoembolization with doxorubicin-eluting beads and sorafenib. Prognosis after diagnosis of recurrence was poor with median a survival of 278 days (range, 114-704).

Conclusions

Global survival, recurrence rate, and pattern of recurrence were similar to previously reported data. Nevertheless, in three patients recurrence was diagnosed >5 years after OLT. Although recurrence was limited and surgically removed in two cases, disease-free survival was poor. Thus, prolonged active surveillance for HCC recurrence beyond 5 years after OLT may be not useful to provide a survival benefit for these patients.     

Hepatocellular Carcinoma and Liver Transplantation: A 12-Year Experience

Background

Orthotopic liver transplantation (OLT) for patients with cirrhosis and concomitant hepatocellular carcinoma (HCC) in early stages is the treatment of choice, with an acceptable recurrence rate and excellent survival.

Aim

We sought to evaluate (1) the accuracy of preoperative imaging; (2) the impact of pre-OLT treatments on survival and recurrence; and (3) the influence of beyond Milan criteria selection on global outcomes.

Methods

We studied a cohort of 65 patients with HCC among 300 consecutive OLTs over a single 12-year experience. We analyzed the overall outcomes of survival and recurrence, the accuracy of preoperative diagnosis and staging the influence of neoadjuvant treatment prior to OLT, and the effect on overall outcomes beyond the Milan criteria in our series.

Results

The 65 transplants were performed for HCC, mostly in association with hepatitis C virus and alcoholic cirrhosis with HTP. At a mean follow-up of 40.32 months, the recurrence rate was 5.7% among the 61 HCC confirmed by histopathology. The overall survival was 30.07. Actuarial survivals at 1, 5, and 10 years were 82%, 77%, and 62%, respectively. Six retransplants occurred among the seven graft losses albeit with poor survival after the second graft. Most explants showed low pTNM stages with favorable microscopic features. Preoperative imaging tests failed to achieve an accurate diagnosis in 15.38% of the series. The role of alpha-fetoprotein (AFP) and hepatic biopsy was irrelevant. Unfavorable histopathologic factors predicted a greater recurrence rate, but had no influence on survival. Neither recurrence nor survival were modified by pre-OLT therapy.

Conclusions

In our series, AFP, hepatic biopsy, and pre-OLT treatment had limited roles. Radiological imaging techniques underestimated HCC staging and lead to a misdiagnosis to an expected degree. Despite these findings, this single institution experience with OLT for HCC showed excellent survivals with a low recurrence rate including cases of patients beyond the Milan criteria.     

Liver Transplantation for Hepatocellular Carcinoma: Results of a Multicenter Study With Common Priorization Criteria

Objective

To evaluate the results of liver transplantation (OLT) performed for hepatocellular carcinoma (HCC) among a multicenter cohort of patients with predefined common inclusion and priorization criteria.

Patients and Methods

Over a 5-year period (January 2002-December 2006), 199 HCC patients underwent OLT in four centers in Andalusia. The morphological (Milan) inclusion criteria were priorized in two consecutive periods, according to the Model for End-stage Liver Disease score: group I, 53 patients (HCC < 2 cm = 24 points; ≥ 2 cm or multinodular = 29 points) and group II, 146 cases (HCC < 3 cm without priorization; HCC ≥ 3 cm or multinodular = 18 points).

Results

Among the 199 HCCs, 186 (93.5%) subjects were transplanted and 13 (6.5%) were excluded. There were 18 cases (9.7%) where the diagnosis was incidental and 168 were known HCC cases; 144 (85.7%) complied with the Milan criteria (Milan+); 24 (14.3%) exceeded there criteria (Milan−). According to preoperative imaging, the number of nodules and tumor mean sizes among the excluded—Milan+ and Milan− groups—were 1.8/5.3 cm, 1.4/3.5 cm, and 2.3/6.7 cm, respectively (P < .001). Percutaneous treatment during listing was delivered to 55% of the excluded cases: 49% of Milan+ and 96% of Milan−. The median time on the list was 88 days for known HCC (53 days for group I, and 97 days for group II), and 172 days for the incidental HCCs. Staging (pTNM) was correct in 64% of cases: 23% were understaged and 13% were overstaged. Overall mortality within the first 90 days was 9%, and transplant patient survival at 5 years was 61%. No differences were observed in survival rates between both study periods, although there were differences between the Milan+ (65%) and Milan− (23%) groups (P < .04). In addition, the difference in the recurrence rates was also significant between the Milan+ (7%), Milan− (24%), and the incidental (25%) groups (P < .02).

Conclusions

A common priorization policy of HCC for OLT based on morphological criteria results in a low exclusion rate on the waiting lists (6.5%). The Milan criteria are still a good cutoff to stratify the risk of recurrence, despite preoperative tumor staging being correct in only two-thirds of cases.     

Liver transplantation for childhood hepatic malignancy: a review of the United Network for Organ Sharing (UNOS) database

Background

Orthotopic liver transplantation (OLT) is the only treatment option for unresectable hepatoblastoma (HB) and hepatocellular carcinoma (HCC) in children. Aggregated outcomes of OLT for these hepatic malignancies have not been evaluated in the United Network for Organ Sharing national database.

Purpose

The purpose of this study was to evaluate graft and patient survival in pediatric OLT recipients with HB and HCC.

Methods

Data from the United Network for Organ Sharing Standard Transplant and Research Files were analyzed and included pediatric (<18 years) OLT recipients with HB or HCC from 1987 to 2004. The effects of diagnosis on pretransplant variables were evaluated using analysis of variance methods or χ² tests, as appropriate. Actuarial survival and effect of diagnosis on survival were determined using Kaplan-Meier methods and log-rank tests.

Results

Since 1987, 152 OLTs have been performed in 135 pediatric patients for HB and 43 OLTs in 41 pediatric patients for HCC. Respective 1-, 5-, and 10-year patient survival after OLT was 79%, 69%, and 66% for HB and 86%, 63%, and 58% for HCC (P = .73). The primary cause of death for both groups was metastatic or recurrent disease, accounting for 54% of deaths in the HB group and 86% in the HCC group (P = .338). Patients with hepatoblastoma were younger (mean age, 2.9 ± 2.5 vs 10.4 ± 4.8 years for the HCC group; P < .001) and more likely to receive a living donor organ (16% vs 4%, P = .03). A greater proportion of the patients with HB had previous abdominal surgery than patients with HCC (63% HB vs 37% HCC, P = .04). Pretransplant medical condition and transplant era were associated with graft and patient survival on univariate and multivariate analysis (all P < .05).

Conclusions

Orthotopic liver transplantation remains a viable option for pediatric patients with unresectable primary hepatic malignancies and results in good long-term survival. Pretransplant medical condition is an important predictor of outcome. Thus, in conjunction with better chemotherapy regimens, earlier evaluation for OLT in patients with unresectable HB and HCC may result in yet further improved long-term survival.     

Estimation of the Harm to the Waiting List as a Crucial Factor in the Selection of Patients With Hepatocellular Carcinoma for Liver Transplantation

Background

Long-term survival rates after orthotopic liver transplantation (OLT) for patients with hepatocellular carcinoma (HCC) of any size and number may now be predicted using the Metroticket calculator. The aim of this study was to evaluate the minimum post-OLT survival threshold that would justify the selection of a patient with HCC for OLT.

Methods

We used a Markov model, recently developed at the University of Michigan, which assumes that a patient with HCC should undergo OLT if his or her transplant benefit is greater than the cumulative harm to the rest of the waiting list (WL). In the base case, we considered a patient with a low survival perspective without OLT (5-year survival rate, 10%). The data sources to construct and validate the model were as follows: the Organ Procurement and Transplantation Network report, and our prospective database.

Results

Our center was generally characterized by lower WL mortalities, although there were lower transplant probabilities for both HCC and non-HCC patients than the average US center. The proportion of HCC patients on the WL was higher in Padua (25%) than in the United States (10%). The calculated harm to the WL was 434 quality-adjusted days of life in Padua, and 957 in the United States (P < .01). The OLT benefit outweighed the harm to the WL when the 5-year post-OLT survival rate was higher than 30% in Padua, and 61% in the United States.

Conclusions

In a decision model including the concepts of transplantation benefit and harm to the WL, the minimum 5-year post-OLT survival threshold justifying the selection of a patient with HCC for OLT in Padua was 30%.     

Sorafenib for the treatment of recurrent hepatocellular carcinoma after liver transplantation?

Background

There are scarce data on the use of sorafenib for the treatment of recurrent hepatocellular carcinoma (HCC) after orthotopic liver transplantation (OLT).

Patients and Methods

Ten patients were treated with sorafenib after OLT following the Italian Drug Agency guidelines: they had well-compensated liver function (Child-Pugh class A in the case of cirrhosis), intermediate-or advanced-stage HCC, good general condition (performance status 0), and not suitable for loco-regional therapies. Patients with HCC recurrence after OLT were treated with sorafenib (400 mg twice daily). Adverse events (AEs) were assessed using National Cancer Institute Common Toxicity Criteria of Adverse Events (NCI-CTCAE) v3.0 with tumor responses evaluated acording to modified Response Evaluation Criteria in Select Tumors) criteria.

Results

Median duration of treatment was 10 months (range, 2-18). Seven patients (70%) received an additionally targeted therapy with mTOR inhibitors as part of their immunosuppressive regimen. Most common grade 3 AEs included diarrhea (50%), hand-foot skin reaction (30%), and fatigue (20%). Sorafenib had to be discontinued in 3 patients (30%) due to AEs and 4 additional patients (40%) required a dose adjustment. No deterioration of liver graft function occurred. Three patients (30%) stopped treatment due to radiological progression of HCC, whereas 3 are still using the drug. Median time to progression was 8 months (range, 2-16). Median survival from start of therapy was 18 months (range, 4- 36).

Conclusion

Our preliminary results suggest that sorafenib is a safe effective therapy for recurrent HCC after OLT.     

Liver transplantation is an alternative treatment of hepatocellular carcinoma beyond the Milan criteria

Background

The decision to perform liver transplantation (LT) or liver resection (LR) for patients with hepatocellular carcinoma (HCC) who are beyond the Milan criteria remains controversial.

Methods

We retrospectively analyzed outcome data for 179 patients with HCC beyond the Milan criteria who were treated with LR (n = 135) or LT (n = 44). Univariate and multivariate Cox proportional hazard models were established. Kaplan-Meier survival curves were generated, and a log-rank test was performed to compare group survival status.

Results

Patients who underwent LR group were significantly older, had a lower TNM stage, and were more likely to have unilateral disease and noncirrhotic liver. Significantly more patients in the LR group had recurrence (53.3% vs 29.5%) or died (61.5% vs 43.2%) than patients in the LT group. Recurrence-free survival rates were 11.9% for the LR group and 61.5% for the LT group. The median overall survival duration showed no statistically difference between the LR group (28.0 months) and the LT group (50.0 months).

Conclusions

LT may be the better choice for patients with HCC beyond the Milan criteria.     

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.