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

Introduction

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

Methods

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

Results

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

Conclusions

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

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.     

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%.     

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.     

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.     

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.     

Outcomes of primary liver cancer in children: an appraisal of experience

Introduction

Hepatoblastoma (HB) and hepatocellular carcinoma (HCC) are the most common primary liver cancers in children. Recent advances in management of pediatric liver cancer have improved disease-specific survival (DSS). This is a review of our experience with childhood liver malignancy over the past 3 decades.

Materials and Methods

A retrospective chart review from 1975 to 2005 identified patients who were 18 years old or younger with a histologically confirmed diagnosis of primary liver cancer. Patients were staged according to the Children's Cancer Group and Pediatric Oncology Group (CCG/POG) system. Patients were followed up prospectively through clinic visits and mail correspondence. Standard statistical methods were used for comparison, risk, and survival analyses.

Results

Fifty-two patients were confirmed to have primary liver cancers, where 24 (46%) patients had HB, 22 (42%) had HCC, 3 (6%) had sarcomas, and 3 (6%) had other histologies. Mean ages at presentation for HB and HCC were 3.2 and 13.1 years old, respectively. The most common presentations were abdominal mass (67%) and pain (40%). Most patients underwent major liver resection (n = 45, 87%), including: lobectomy (n = 25, 48%), and trisegmentectomy (n = 11, 21%). Three patients underwent liver transplantation (n = 3, 6%) for advanced local disease. Forty-five (87%) received primary or neoadjuvant and/or adjuvant chemotherapy. Patients had the following CCG/POG stages: I (n = 31, 60%), II (n = 6, 11.5%), III (n = 9, 17%), and IV (n = 6, 11.5%). Complete gross resection (stage I and II) was achieved in 37 (71%) patients. The perioperative mortality and morbidity rates were 0% and 29%, respectively. Patients with complete resection had significantly better 5-year DSS and median survival compared with incomplete gross resection: 62% vs 9% and 216 vs 18 months, P < .001. Patients treated during the period 1995-2005 had better 5-year DSS and median survival compared with those treated during 1975-1994: 68% vs 32% and 117 vs 27 months, P = .032. All 3 patients who underwent transplantation for conventionally unresectable disease are alive without disease recurrence (follow-up period, 1-15 years).

Conclusion

Complete resection of the pediatric primary liver tumors remains the cornerstone of treatment to achieve cure. Major liver resection can be performed with minimal perioperative mortality and morbidity. Patients with HB appeared to have better survival compared with patients with HCC, and there was significant improvement in the DSS of children treated in the recent decade. Liver transplantation in conjunction with chemotherapy may have an increasing role in the management of locally advanced primary liver cancers.     

Hepatocellular Carcinoma in Unrelated Viral Cirrhosis: Long-Term Results After Liver Transplantation

Introduction

Chronic viral hepatitis is considered to be the most significant risk factor for development of hepatocellular carcinoma (HCC). Nevertheless, about 5%-15% of HCC occur in noncirrhotic or virus-unrelated cirrhotic patients. The natural history of HCC in terms of incidence, clinical features, and tumor progression differs according to the underlying cancerogenic factors and differences in hepatocarcinogenetic pathways. Little is know about the relationship between HCC outcomes after liver transplantation (OLT) and the primary liver disease. We retrospectively analyzed the outcomes of patients transplanted due to HCC in settings of either virus—related or virus-unrelated cirrhosis.

Patients and Methods

From January 2000 to December 2007, 179 patients underwent OLT due to HCC: 157 (87.8%) affected by virus-related (group A) and 22 (12.2%) virus-unrelated cirrhosis (group B). We analyzed patient characteristics including demographics, tumor features, downstaging treatments, and recurrences.

Results

At a mean follow-up of 41.2 months, the 3- and 5-year overall long-term survivals between group A versus group B were 81% versus 75% and 85% versus 78.4% respectively (P = NS). The 3- and 5-year disease-free survivals between group A versus group B were 90.8% versus 89.6% and 85.6% versus 85.6%, respectively (P = NS). After OLT, HCC recurrences occurred in 14 group A (14/157, 8.9%) and 4 patients (4/22, 18.1%) group B subjects.

Discussion

Our data demonstrated that after OLT, HCC outcomes were not different between patients with virus-related or -unrelated cirrhosis. The direct oncogenetic role played by hepatitis B and C appear to not be associated with a greater risk to develop HCC recurrence.     

Prospective Validation of a New Priority Allocation Model for Liver Transplant Candidates: An Interim Analysis

Background

The system that controls the waiting list (WL) and organ allocation for liver transplantation (OLT) seeks to achieve 3 main goals: objectivity, low dropout risks and good post-OLT results. We sought to prospectively validate a priority allocation model that is believed to achieve objectivity without penalizing dropout risk and post-OLT results.

Methods

We evaluated a study group of 272 patients enrolled in 2006-2007. WL candidates were divided into 2 categories: cirrhotic patients classified according to Model for End-Stage Liver Disease (MELD) score (MELD list and patients with hepatocellular carcinoma (HCC) organized according to a specific score (non-MELD list). The allocation algorithm for donor-recipient match assigned an optimal graft to the first MELD candidate with a MELD score of ≥20; a suboptimal graft, to the first non-MELD patient. A respective control group of 327 patients transplanted from 2003-2006 was characterized by a unique WL with a free allocation policy. We performed an interim analysis of this prospectively controlled study.

Results

Although the study group showed a lower percentage of OLT (P < .05) than the control group (37% vs 45%), it selected patients for OLT based on a higher MELD score (P < .05), thus obtaining similar dropout, post-OLT survivals, and intention-to-treat (ITT) survival probabilities as the controls. Among MELD patients, we observed a significantly reduced dropout and better ITT survival profiles than those of the control group (P = .02), whereas the similar results were delivered among non-MELD patients (P > .05). Among patients with a MELD score of ≥20, the prevalences of suboptimal grafts (0% vs 48%) and of early graft losses (0% vs 21%) were lower in the study than in the control group (P < .05).

Conclusions

We prospectively validated a priority allocation model based on objective criteria that achieved high ITT survival rates.     

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.     

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.     

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.     

Antitumor efficacy of Mammalian target of rapamycin inhibitor therapy in liver transplant recipients with oncological disease: a case-control study

Introduction

The reported incidences of de novo malignancy following orthotopic liver transplantation (OLT) are significantly greater than those in the general population. We have analyzed the efficacy of mammalian target of rapamycin inhibitor (mTORi) as immunosuppressant therapy in patients with de novo malignancies or those engrafted because of a primary liver cancer.

Methods

We performed a case-control study of patients with hepatocellular carcinoma (HCC; n = 119), cholangiocarcinoma (n = 1) or de novo malignancies (n = 73). Thirty-seven patients with these tumors were treated with mTORi, and 167, with calcineurin inhibitors (CNI). Switching to mTORi was performed progressively, withdrawing the CNI over 15 days, until obtaining levels of 5-10 ng/dL.

Results

No incidence of rejection, serious adverse events, or death was observed with an overall actuarial survival of 68.5% in the mTORi group versus 45.7% among the CNI group. Overall rates of tumor recurrence were 15.2% and 36.8%, respectively (P < .05). Among patients with HCC, survival was 100% of mTORi with and 61.5% among CNI patients, with tumor recurrence rates of 6.2% and 19.1%, respectively (P < .05).

Discussion

Surprising differences in survival and tumor recurrence rates were observed among the mTORi-treated group compared with controls. Switching from CNI to mTORi immunosuppressant therapy appeared to be safe. It seems to be reasonable to employ this strategy in liver transplant patients with primary hepatic or “de novo” neoplasms.     

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.     

Factors associated with sustained virological response in liver transplant recipients with recurrent hepatitis C

Background

Antiviral therapy has achieved sustained virological response (SVR) in less than one third of orthotopic liver transplantation (OLT) patients with recurrent hepatitis C.

Aim

The aim of this study was to identify predictors of SVR in OLT patients treated with pegylated interferon and ribavirin (PEG+RBV) for recurrent hepatitis C virus (HCV).

Methods

We analyzed data from our transplantation database for 62 subjects treated with PEG+RBV between August 2001 and September 2008. After univariate examination for factors known to be associated with SVR, significant associations (P < .05) were probed using multivariate logistic regression. Kaplan-Meier patient and graft survival analyses were compared between patients with (n = 19; 30.6%) versus without SVR.

Results

On univariate analysis, longer duration of therapy, low pretreatment HCV RNA (<1 million IU/mL), and early virological response (EVR) were associated with SVR. On multivariate analysis, only low pretreatment HCV RNA predicted SVR. Patient survival was significantly higher in the SVR group.

Conclusions

Covariates associated with SVR among OLT patients with recurrent HCV were similar to the pretransplantation group. Potentially modifiable risk factors, such as obesity, diabetes mellitus, and metabolic syndrome, were not significant predictors of treatment response. Patient survival was associated with SVR, highlighting the impact of successful HCV therapy on long-term post-OLT outcomes.     

Laparoscopic Ultrasound-Guided Radiofrequency Ablation as a Bridge to Liver Transplantation for Hepatocellular Carcinoma: Preliminary Results

Introduction

The aim of this study was to assess the impact of laparoscopic thermoablation (LTA) as a neoadjuvant therapy prior to orthotopic liver transplantation (OLT) for hepatocellular carcinoma (HCC).

Methods

Between January 2008 and January 2009, 12 consecutive patients, including 10 males and 2 females with unresectable HCC within liver cirrhosis, were treated with LTA under ultrasound (US) guidance. Most patients were in Child-Pugh class B (54.1%) with a mean age of 60.7 ± 7.74 years (range, 45-69; median, 60).

Results

The LTA procedure was completed in all patients with thermoablation of 23 HCC nodules. LTA identified 4 new malignant lesions (20%) undetected by preoperative imaging (<0.5 cm). The mean length of surgery was 96 minutes (range, 45-118). Six procedures were performed in 4 patients. No postoperative hepatic insufficiency was reported. The mean hospital stay was 4.5 days; no postoperative morbidity was reported. Complete tumor necrosis was achieved in 19/23 thermoablated nodules (82.6%) as evidenced computed tomography (CT) scan by at 3 weeks after the treatment. All patients underwent OLT without complications. The histology of the native liver showed complete necrosis in 17/23 (74%) treated nodules.

Discussion

There is currently no convincing evidence that LTA allows one to expand the current selection criteria for OLT, nor that LTA decreases dropout rates on the waiting list. However, LTA does not increase the risk of postoperative complications. There is insufficient evidence that LTA offers any benefit when used prior to OLT either for early or for advanced HCC.     

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.     

Development of Lymphoproliferative Disease After Liver Transplantation

Introduction

Malignancies are a serious long-term complication among liver transplant recipients, with an overall incidence of 4.5%-15%. Posttransplantation lymphoproliferative disease (PTLD) is one of the leading causes of late death. Its development is related to complex interactions between immunosuppressive drugs and environmental agents. The aim of this study was to analyze risk factors for PTLD and survival after orthotopic liver transplantation (OLT) compared with solid tumors.

Patients and Methods

We undertook a retrospective review of the clinical histories of adult patients who underwent OLT between July 1986 and February 2001, and who had been followed until 2005. This study comprised 528 adult recipients who survived more than 2 months after OLT. We excluded pediatric, partial-organ, and multiorgan recipients.

Results

No differences were observed concerning gender, viral etiology of hepatitis, calcineurin inhibitor regimen, or steroid maintenance period. Treated acute rejection episodes accounted for 53.3% of patients who developed PTLD compared with 47.3% in the control group (P = .787). Patients with solid tumors were older at the time of diagnosis than those with PTLD (57.5 ± 8.13 years vs 48.8 ± 13.9; P = .002). The overall mortality rate for PTLD was 55.5%, which did not differ significantly from solid tumors.

Conclusions

PTLD develops in younger patients after OLT. Various immunosuppressive regimens do not seem to influence the incidence of PTLD or other solid tumors.     

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.