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.     

Liver Transplantation After Downstagings of Ruptured Advanced Hepatocellular Carcinoma in Cirrhotic Liver: Is It Advisable? A Case Report

Spontaneous rupture of hepatocellular carcinoma (HCC), defined as T4 in TNM stage by the American Joint Committee on Cancer (eighth edition), is a serious life-threatening complication. Effective treatment remains challenging because of a high 1-month mortality, a short median survival, and the potential of peritoneal metastasis. We reported on a case that received a living related donor liver transplantation (LDLT) after successful consecutive downstaging therapies. A 63-year-old man with alcohol-related liver cirrhosis and multiple HCC developed spontaneous rupture and hemoperitoneum. He received 3 sessions of transcatheter hepatic arterial chemoembolization and target therapy with sorafenib. Computed tomography scans and magnetic resonance imaging after 11 months of treatment showed that the patient's HCCs fulfilled the Milan criteria and the University of California San Francisco criteria prior to LDLT. The perioperative course was rather smooth. After discharge, interval follow-up computed tomography studies of chest and liver and a whole-body bone scan showed no tumor recurrence or metastasis up to 20 months post-operation. Successful downstaging therapies of ruptured HCC to fulfill Milan criteria to receive liver transplantation is advisable in highly selected patients.     

Comparison Between Living Donor Liver Transplantation Recipients Who Met the Milan and UCSF Criteria After Successful Downstaging Therapies

Background and Aims

Various downstaging therapies were introduced to liver recipients who could not meet the relative criteria for liver transplantation, and many endpoints were reported. The most common criteria used were the Milan criteria and the University of California, San Francisco (UCSF) criteria. However, no comparison was made between them, and we attempted to find possible differences between the living donor liver transplantation (LDLT) patients who met the Milan criteria and those who met the UCSF criteria after accepting preoperative downstaging therapies.

Materials and Methods

We performed a retrospective study of all 72 patients at our center from January 2003 to March 2009 who were diagnosed with advanced hepatocellular carcinoma but accepted various downstaging therapies. Some patients met the Milan criteria (group 1), and some met the UCSF criteria (group 2) but not the Milan criteria. We collected the data from the two groups and then compared the preoperative demographic data, downstaging therapies, intraoperative data from LDLT, and the recovery and complications after LDLT. Survival rates were compared using Kaplan?CMeier analysis.

Results

Only 44 patients (61.1?%) met the criteria for liver transplantation, 21 cases met the Milan criteria (group 1), and 23 cases met the UCSF criteria (group 2) but not the Milan criteria. All of the 44 patients accepted right lobe living liver donor liver transplantation in our center. The difference in the baseline characteristics between the two groups did not reach statistical significance. The mean number of downstaging treatments per patient was 1.81?±?0.35 in group 1 and 1.83?±?0.41 in group 2 (P?=?0.928). Most of the patients received only one downstaging treatment, and transcatheter arterial chemoembolization (TACE) was the most common downstaging therapy. Four patients suffered complications after downstaging therapies: intra-abdominal hemorrhage after right hepatectomy, upper gastrointestinal hemorrhage after TACE, biliary fistula after resection, and hand?Cfoot syndrome after taking sorafenib. All complications after LDLT, classified according to the Clavien?CDindo system, were compared within the two groups, and the calculated score of the complications in group 1 was 1.48?±?1.63, which was greater than that of group 2 (1.39?±?1.64), but this difference did not reach statistical significance (P?=?0.865). The 1-, 3-, and 5-year survival rates were 90.4, 76.2, and 71.4?% in group 1 and 91.3, 73.9, and 69.6?% in group 2, respectively (P?>?0.05). Seven patients (three in group 1 and four in group 2) had tumor recurrence after a median follow-up period of 72?months. The pathology findings were not different between the two groups.

Conclusion

Recipients who meet the Milan or UCSF criteria after accepting successful preoperative downstaging therapy in LDLT can achieve the same result.     

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.     

Use of Yttrium-90 Microsphere Radioembolization of Hepatocellular Carcinoma as Downstaging and Bridge Before Liver Transplantation: A Case Report

Background and objective

Yttrium-90 microspheres radioembolization (Y90-RE) has been recently introduced as promising modality of treatment in patients with hepatocellular carcinoma (HCC) who are not otherwise candidates for local ablation, surgical resection, or liver transplantation (OLT). However, its use in downstaging HCC or as a bridge for OLT is still unclear. Herein, we have presented a case where Y90-RE was used to both downstage and to serve as a bridge for OLT.

Case Report

We report a 54-year-old lady who was known to have hepatitis B virus cirrhosis in addition to two focal hepatic lesions in segments 5 and 8, measuring 1.5 and 7.5 cm, respectfully. Extrahepatic spread was thoroughly ruled out. This tumor was clearly beyond both the Milans and University of California San Francisco criteria for OLT in HCC patients; therefore, we offered the patient Y90-RE in an attempt to downstage the tumor and as a bridge for OLT. Y90-RE was performed targeting the large lesion; the patient underwent cadaveric OLT 2 months thereafter. Gross examination of the explant showed necrotic tumor with obvious signs of irradiation-induced damage. Microscopic examination of the explant showed Y90 microspheres trapped in the large tumor with near-complete tumor necrosis. This patient completed 1-year post-OLT follow-up with no signs of tumor recurrence.

Conclusions

The use Y90-RE in HCC may be useful for downstaging or as a bridge to liver transplantation.     

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

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

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

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

Living donor liver transplantation of the right lobe for hepatocellular carcinoma in cirrhosis in a European center.

Living donor liver transplantation of the right lobe might offer the possibility to extend the eligibility criteria of patients with hepatocellular carcinoma (HCC) in cirrhosis without penalizing patients who are waiting for a graft from a deceased donor. From 1988 to 2005, surgical treatment of HCC was performed in 580 patients (187 transplantation, 393 resection) in a European center. In the transplantation group, 21 patients with HCC in cirrhosis underwent LDLT (11% of all transplantations for HCC; 22% of 96 LDLT). Solitary HCC were accepted irrespective of their diameter unless vascular invasion was detectable. Multiple HCC nodes were considered acceptable up to a diameter of the largest node of 6 cm and a total tumor diameter of 15 cm. The median follow-up period was 26 months (range, 1-65 months). Vascular invasion had occurred in 12 patients (57%). One patient (4.8%) died within 60 days after transplantation from sepsis. Rates of 3-year survival and 3-year recurrence-free survival were 68% and 64%, respectively. Overall 3-year survival rates in patients with HCC in cirrhosis not meeting the Milan criteria (n = 13) or the San Francisco criteria (n = 8) were 62% and 53%, respectively. LDLT is a safe procedure. However, small sample sizes do not yet permit a definitive comparison to be made between the former results obtained after cadaveric donation. So far, the outcome of the patients is in favor of a careful extension of the selection criteria for HCC in cirrhosis.     

Downstaging Advanced Hepatocellular Carcinoma to the Milan Criteria May Provide a Comparable Outcome to Conventional Milan Criteria

Background and Aims

Many hepatocellular carcinoma (HCC) patients met the appropriate criteria and accepted liver transplantation after successful downstaging therapies; however, the outcome in these patients is unclear. We aim to compare the outcome of patients meeting the Milan criteria at the beginning and after successful downstaging therapies.

Patients and Methods

Between July 2001 and January 2013, 112 patients were diagnosed with early-stage HCC that met the Milan criteria. Of these patients, 58 patients did not meet the Milan criteria initially but did after successful downstaging therapies. We retrospectively collected and then compared the baseline characteristics, postoperative complications, survival rate, and tumor recurrence rate of these two groups. Kaplan–Meier analyses were used to estimate the long-term overall survival and tumor-free survival in these patients.

Results

No significant differences were observed between the two groups with respect to baseline donor and recipient characteristics. The downstaging Milan group showed similar tumor characteristics compared to the conventional Milan group, except the downstaging group had better tumor histopathologic grading (P?=?0.027). The 1-, 3-, and 5-year overall survival rates were comparable at 91.4, 82.8, and 70.7 %, respectively, in the downstaging Milan criteria and 92.0, 85.7, and 74.1 %, respectively, according to the initial Milan criteria (P?=?0.540). The 1-, 3-, and 5-year tumor-free survival rates between the two groups were not statistically significant (P?=?0.667).

Conclusion

Successful downstaging therapies can provide a comparable posttransplantation overall survival and tumor-free survival rates after liver transplantation.     

Adult living donor liver transplantation for patients with hepatocellular carcinoma: extending UNOS priority criteria

INTRODUCTION: For patients with hepatocellular carcinoma (HCC) in particular, living donor liver transplant (LDLT) improves access to transplant. We report our results in 36 patients with HCC who underwent LDLT with a median follow-up >1 year. METHODS Underlying diagnoses included: hepatitis C (24), hepatitis B (9), cryptogenic cirrhosis (1), hemochromatosis (1), and primary biliary cirrhosis (1). Patients with tumors >or= 5 cm received IV doxorubicin intraoperatively and 6 cycles of doxorubicin at 3-week intervals. Patients were followed with CT scan and alpha-fetoprotein levels every 3 months for 2 years posttransplant. Mean waiting time, pretransplant treatment, tumor variables, and survival were analyzed. Univariate and multivariate analysis were done to analyze tumor variables; Kaplan-Meier and log rank were used to compare survivals. P < 0.05 was considered significant. RESULTS Mean wait for LDLT was 62 days, compared with 459 days in 50 patients with HCC transplanted with cadaveric organs during the same time period (P = 0.0001). At median follow-up of 450 days, there have been 10 deaths due to non-tumor-related causes and 3 deaths from recurrence; recurrence has also been observed in 3 other patients. On univariate and multivariate analysis, bilobar distribution was the only significant tumor variable (P = 0.03, log rank = 0.02). Fifty-three percent of patients exceeded UNOS priority criteria. One- and two-year patient survivals were 75% and 60%, respectively. Freedom from recurrence at 365 and 730 days was 82% and 74%, respectively. Overall and in patients with HCC > 5 cm (n = 12), there were no statistically significant differences in survival or in freedom from recurrence between recipients of living donor and cadaveric grafts. CONCLUSION Although one third of patients had tumors > 5 cm, the incidence of recurrence as well as patient survival and freedom from recurrence are comparable to results after cadaveric transplant. LDLT allows timely transplantation in patients with early or with large HCC.     

Liver Transplantation for Hepatocellular Carcinoma: Validation of the UCSF-Expanded Criteria Based on Preoperative Imaging

We previously suggested that in patients with heptocellular carcinoma (HCC), the conventional Milan criteria (T1/T2) for orthotopic liver transplantation (OLT) could be modestly expanded based on pathology (UCSF criteria). The present study was undertaken to prospectively validate the UCSF criteria based on pretransplant imaging. Over a 5-year period, the UCSF criteria were used as selection guidelines for OLT in 168 patients, including 38 patients exceeding Milan but meeting UCSF criteria (T3A). The 1- and 5-year recurrence-free probabilities were 95.9% and 90.9%, and the respective survivals without recurrence were 92.1% and 80.7%. Patients with preoperative T1/T2 HCC had 1- and 5-year recurrence-free probabilities of 95.7% and 90.1%, respectively, versus 96.9% and 93.6%, respectively, for preoperative T3A stage (p = 0.58). Under-staging was observed in 20% of T2 and 29% of T3A HCC (p = 0.26). When explant tumor exceeded UCSF criteria (15%), the 1- and 5-year recurrence-free probabilities were 80.4% and 59.5%, versus 98.6% and 96.7%, respectively, for those within UCSF criteria (p < 0.0001). In conclusion, our results validated the ability of the UCSF criteria to discriminate prognosis after OLT and to serve as selection criteria for OLT, with a similar risk of tumor recurrence and under-staging when compared to the Milan criteria.     

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.     

A Comparative Analysis of Transarterial Downstaging for Hepatocellular Carcinoma: Chemoembolization Versus Radioembolization

Chemoembolization and other ablative therapies are routinely utilized in downstaging from United Network for Organ Sharing (UNOS) T3 to T2, thus potentially making patients transplant candidates under the UNOS model for end-stage liver disease (MELD) upgrade for hepatocellular carcinoma (HCC). This study was undertaken to compare the downstaging efficacy of transarterial chemoembolization (TACE) versus transarterial radioembolization. Eighty-six patients were treated with either TACE (n = 43) or transarterial radioembolization with Yttrium-90 microspheres (TARE-Y90; n = 43). Median tumor size was similar (TACE: 5.7 cm, TARE-Y90: 5.6 cm). Partial response rates favored TARE-Y90 versus TACE (61% vs. 37%). Downstaging to UNOS T2 was achieved in 31% of TACE and 58% of TARE-Y90 patients. Time to progression according to UNOS criteria was similar for both groups (18.2 months for TACE vs. 33.3 months for TARE-Y90, p = 0.098). Event-free survival was significantly greater for TARE-Y90 than TACE (17.7 vs. 7.1 months, p = 0.0017). Overall survival favored TARE-Y90 compared to TACE (censored 35.7/18.7 months; p = 0.18; uncensored 41.6/19.2 months; p = 0.008). In conclusion, TARE-Y90 appears to outperform TACE for downstaging HCC from UNOS T3 to T2.     

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.     

Liver Transplantation in Patients With Hepatocellular Carcinoma Outside the Milan Criteria After Downstaging: Is It Worth It?

Background

The outcome of orthotopic liver transplantation (OLT) for hepatocellular carcinoma (HCC) is excellent if it is performed within the Milan criteria (ie, single tumor less than 5 cm or 3 tumors less than 3 cm each one and no macrovascular invasion). However, after a few studies, it has become possible to have a similar survival expanding those criteria. The aim of this study is to evaluate the survival of patients with advanced HCC who, after downstaging, did not met the Milan criteria although they were within the “up to seven” benchmark, and were transplanted at our center in the last 5 years.

The role of living-donor liver transplantation in surgical treatment for hepatocellular carcinoma

Background/Purpose The role of living-donor liver transplantation (LDLT) in the surgical treatment of patients with hepatocellular carcinoma (HCC) has not been established as yet. Methods Preliminary experience gained from 24 patients who underwent LDLT for HCC between March 2002 and November 2004, and the results of the 131 patients who underwent hepatic resection (HR) for HCC between January 1990 and December 2003 were retrospectively analyzed. The exclusion criteria for LDLT for HCC included extrahepatic metastasis and major vascular invasion. Results (1) LDLT: the median age of the patients was 57 years and the Child-Pugh grades (A/B/C) of the patients were 6, 12, and 6, respectively. The tumor size was 3 cm or less in 15 patients, multinodular tumors were present in 23 patients, and 11 patients (45.8%) met the Milan Criteria. The overall 2-year survival rate was 72.3%, without a significant difference as to whether or not patients met the Milan criteria. (2) HR: on multivariate analysis, the Child-Pugh grade, the presence of cirrhosis, and the number of tumor nodules were considered as independent risk factors for unfavorable survival (P < 0.05). The 84 patients who met the Milan criteria and were Child-Pugh grade A had a 5-year survival rate of 71.3%; this was significantly better than those of the other patients (P < 0.005). Among the 57 patients with intrahepatic recurrence, 18 patients who were Child-Pugh grade A, met the Milan criteria, and were treated by re-resection or ablation therapy achieved a significantly better 5-year survival rate, of 73.1%, as compared to 19.7% in the other 39 patients (P < 0.0045). Conclusions HR could be a first-line treatment with a favorable prognosis for patients who have resectable HCC, preserved liver function, and who meet the Milan criteria. Salvage LDLT could be employed in patients with recurrent tumors that cannot be controlled by conventional treatment or in patients in whom liver function has deteriorated to Child-Pugh grade B or C.     

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.     

Liver transplantation for adult patients with hepatocellular carcinoma in Korea: comparison between cadaveric donor and living donor liver transplantations.

Current selection criteria of liver transplantation (LT) for patients with hepatocellular carcinoma (HCC) were derived from the outcomes of cadaveric donor LT (CDLT). We tried to assess the applicability of such criteria to living donor LT (LDLT) through a comparative study between CDLT and LDLT. We analyzed the outcomes of 312 HCC patients who underwent LT at 4 Korean institutions during 1992 to 2002. There were no gross differences of tumor characteristics between CDLT group (n = 75) and LDLT group (n = 237). Overall 3-year survival rate (3-YSR) was 61.1% after CDLT and 73.2% after LDLT including 38 cases of perioperative mortality. Comparison of HCC recurrence curves did not reveal any statistical difference between these 2 groups. Patient survival period till 50% mortality after HCC recurrence was 11 months after CDLT and 7 months after LDLT. Significant risk factors for HCC recurrence were alpha-fetoprotein level, tumor size, microvascular invasion, gross major vessel invasion, bilateral tumor distribution, and histologic differentiation in the LDLT group on univariate analysis, and tumor size, gross major vessel invasion, and histologic differentiation on multivariate analysis. Milan criteria were met in 70.4%: Their 3-YSR was 89.9% after CDLT and 91.4% after LDLT with exclusion of perioperative mortality. University of California San Francisco criteria were met in 77.7%: Their 3-YSR was 88.1% after CDLT and 90.6% after LDLT. In conclusion, we think that currently available selection criteria for HCC patients can be applicable to LDLT without change of prognostic power.     

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.