Downstaging Of Hepatocellular Carcinoma Research Articles

Milan 기준을 넘는 간세포암종에서 방사선색전술, 간동맥 화학요법 및 정위체부방사선치료를 통한 Down-staging 후 성공적인 생체간이식을 시행한 1예

Milan 기준을 넘는 간세포암종에서 방사선색전술, 간동맥 화학요법 및 정위체부방사선치료를 통한 Down-staging 후 성공적인 생체간이식을 시행한 1예

Hepatectomy after down-staging of hepatocellular carcinoma with portal vein tumor thrombus using chemoradiotherapy: A retrospective cohort study

BackgroundThis study evaluates the survival benefit and safety of hepatectomy after down-staging by 3-dimensional conformal radiation therapy (3D-CRT) for major portal vein tumor thrombus (PVTT) combined with hepatic arterial infusion chemotherapy (HAIC) for advanced hepatocellular carcinoma (HCC). MethodsFifty-two patients with unresectable advanced HCC treated with HAIC combined with 3D-CRT for PVTT, from January 2002 to March 2015, were analyzed in this retrospective study. Hepatectomy was offered to patients if, based on radiologic findings, all gross lesions were considered resectable. The safety of hepatectomy was investigated and overall survival (OS) was compared between the resection group (n = 7) and non-resection group (n = 43). ResultsOS was significantly higher in the resection group than in the non-resection group. Results of multivariate analysis identified conversion to surgery (hazard ratio, 0.35; 95% confidence interval, 0.10–0.99; P = 0.048) as an independent factor influencing OS. There were no serious postoperative complications and no case of mortality in patients who underwent hepatectomy. ConclusionsOur findings suggest that hepatectomy after down-staging by 3D-CRT for PVTT combined with HAIC for advanced HCC is safe and results in good long term outcome.

Liver transplantation for hepatocellular carcinoma.

Over the last several years, liver transplantation has evolved to become a widely used treatment for hepatocellular carcinoma (HCC). The criteria used were developed in order to have acceptable outcomes for transplant with survival similar to other indications for transplant. These criteria are discussed in detail along with alternate options, including surgical resection and downstaging of HCC in cirrhotics. Technical considerations of liver transplantation must be considered, and living donor liver transplant is a possibility for treatment.

Predictors of Successful Downstaging of Hepatocellular Carcinoma Outside Milan Criteria

Patients with hepatocellular carcinoma (HCC) outside Milan criteria (MC) may be candidates for liver transplantation (LT) after successful downstaging. Factors that predict successful downstaging are unclear. We aimed to identify the predictors of successful downstaging of HCC in patients outside MC. We performed a retrospective cohort study on consecutive patients with HCC outside MC who received downstaging with locoregional therapy. Clinical and laboratory variables, tumor characteristics including total tumor volume (TTV) and up-to-7 criteria were recorded. We performed univariate and multivariate logistic regression analyses to identify variables associated with successful downstaging. Of 675 patients with HCC, 90 patients outside MC received downstaging. Fifty-three (59%) patients were successfully downstaged, 37 (41%) failed downstaging. University of California at San Francisco criteria, α-fetoprotein, up-to-7 criteria, TTV, and platelet count were predictors of successful downstaging on univariate analysis. Total tumor volume was an independent predictor of successful downstaging on multivariate logistic regression (P = 0.04, area under receiver operating characteristic curve 0.89 (95% confidence interval, 0.82-0.96). Fifty-two (76%) of 68 patients with TTV less than 200 cm were successfully downstaged, whereas only 1 (4.5%) of 22 patients with TTV greater than 200 cm were successfully downstaged. Forty-five (50%) patients underwent LT. Kaplan-Meier survival rates at 1 and 5 years post-LT were 95.3% and 79.4%, respectively. Patients who were successfully downstaged had better survival than patients who failed downstaging (P < 0.01). Total tumor volume is a good predictor of successful downstaging of HCC. Patients with TTV less than 200 cm may be considered good candidates for downstaging. Further studies with larger cohort of patients are needed to validate this approach in patients with HCC outside Milan.

Favorable Long-term Outcome in Patients Submitted to Liver Transplantation After Downstaging of Hepatocellular Carcinoma According to a Brazilian Selection Protocol.

In October 2008, the Brazilian Ministry of Health authorized listing of downstaged hepatocellular carcinoma (HCC) for liver transplantation, according to a standardized protocol. The aim of this study was to compare the outcome of patients submitted to liver transplantation after downstaging of HCC with the results other standard indications in Brazil. We conducted a retrospective analysis of 2,667 adult 1st elective deceased-donor liver transplantations registered at the database of the Transplant Notification Center of the São Paulo State Health Secretariat. These cases are classified into 3 groups: "cirrhosis," including 1,709 patients transplanted because of end-stage liver disease; "Milan-HCC," including 873 HCC patients initially meeting the Milan criteria; and "downstaging" group, including 85 HCC patients submitted to tumor downstaging to the Milan criteria before liver transplantation. One-, 3-, 5-, and 6-year patients survivals were, respectively, 82.7%, 72.0%, 66.1%, and 66.1%, in the "downstaging" group and 76.7%, 68.4%, 63.9%, and 63.5% in the "Milan-HCC" group (P= .483). At the same time intervals, patient survivals were 67.8%, 62.9%, 60.9%, and 60.2% in the "cirrhosis" group. These probabilities were significantly lower than those of both "downstaging" (P= .047) and "Milan-HCC" (P=.001) groups. Patients submitted to liver transplantation after downstaging of HCC, according to a Brazilian selection protocol, present long-term outcomes similar to HCC patients initially within the Milan criteria and better survival than recipients with end-stage liver disease.

Is Salvage Liver Resection Necessary for Initially Unresectable Hepatocellular Carcinoma Patients Downstaged by Transarterial Chemoembolization? Ten Years of Experience.

This study evaluated long-term outcomes of salvage surgery as additional therapy following downstaging of hepatocellular carcinoma (HCC) with transarterial chemoembolization (TACE) in patients with initially unresectable HCC. A retrospective analysis was performed of 831 consecutive patients with unresectable HCC who underwent TACE as initial treatment between June 2004 and December 2014. Of these, 82 patients with downstaged resectable HCC were enrolled in this study: 43 received salvage surgery (S group) and the remaining 39, who refused salvage resection, were the control group (T group). The primary endpoint was overall survival (OS). The median OS in the S and T groups was 49 and 31 months, respectively (p = .027). The 2-, 4-, and 5-year survival rates were 93%, 47%, and 26% in the S group and 74%, 18%, and 10% in the T group, respectively (p = .019). Treatment modality (hazard ratio [HR], 0.337; 95% confidential interval [CI], 0.184-0.616; p < .001) and response to TACE (complete vs. partial; HR, 3.154; 95% CI, 1.709-5.822; p < .001) were independent prognostic factors for survival. The median OS for patients in the complete response and partial response (PR) subgroups was 50 and 49 months, respectively, in the S group and 54 and 24 months, respectively, in the T group (p = .699 and p < .001, respectively). The median OS for HCC patients with macroscopic vascular invasion (MVI) was 58 and 30 months in the S and T groups, respectively (p = .024). Salvage surgery after downstaging of unresectable HCC had a survival benefit only for patients with MVI or a PR to TACE. The results of this study suggest that salvage liver resection after downstaging of unresectable hepatocellular carcinoma in patients with a complete response to transarterial chemoembolization (TACE) has a comparable long-term outcome in this good-prognosis group. Salvage liver resection may provide a better long-term outcome compared with TACE alone, but only in patients with macroscopic vascular invasion or those with a partial response to TACE.

Living Donor Liver Transplantation for Advanced Hepatocellular Carcinoma with Portal Vein Tumor Thrombosis after Concurrent Chemoradiation Therapy.

Locally advanced hepatocellular carcinoma (HCC) with portal vein thrombosis carries a 1-year survival rate <10%. Localized concurrent chemoradiotherapy (CCRT), followed by hepatic arterial infusion chemotherapy (HAIC), was recently introduced in this setting. Here, we report our early experience with living donor liver transplantation (LDLT) in such patients after successful down-staging of HCC through CCRT and HAIC. Between December 2011 and September 2012, eight patients with locally advanced HCC at initial diagnosis were given CCRT, followed by HAIC, and underwent LDLT at the Severance Hospital, Seoul, Korea. CCRT [45 Gy over 5 weeks with 5-fluorouracil (5-FU) as HAIC] was followed by HAIC (5-FU/cisplatin combination every 4 weeks for 3–12 months), adjusted for tumor response. Down-staging succeeded in all eight patients, leaving no viable tumor thrombi in major vessels, although three patients first underwent hepatic resections. Due to deteriorating liver function, transplantation was the sole therapeutic option and offered a chance for cure. The 1-year disease-free survival rate was 87.5%. There were three instances of post-transplantation tumor recurrence during follow-up monitoring (median, 17 months; range, 10–22 months), but no deaths occurred. Median survival time from initial diagnosis was 33 months. Four postoperative complications recorded in three patients (anastomotic strictures: portal vein, 2; bile duct, 2) were resolved through radiologic interventions. Using an intensive tumor down-staging protocol of CCRT followed by HAIC, LDLT may be a therapeutic option for selected patients with locally advanced HCC and portal vein tumor thrombosis.

Downstaging of hepatocellular cancer before liver transplant: long-term outcome compared to tumors within Milan criteria.

We report on the long-term intention-to-treat (ITT) outcome of 118 patients with hepatocellular carcinoma (HCC) undergoing downstaging to within Milan/United Network for Organ Sharing T2 criteria before liver transplantation (LT) since 2002 and compare the results with 488 patients listed for LT with HCC meeting T2 criteria at listing in the same period. The downstaging subgroups include 1 lesion >5 and ≤8 cm (n = 43), 2 or 3 lesions at least one >3 and ≤5 cm with total tumor diameter ≤8 cm (n = 61), or 4-5 lesions each ≤3 cm with total tumor diameter ≤8 cm (n = 14). In the downstaging group, 64 patients (54.2%) had received LT and 5 (7.5%) developed HCC recurrence. Two of the five patients with HCC recurrence had 4-5 tumors at presentation. The 1- and 2-year cumulative probabilities for dropout (competing risk) were 24.1% and 34.2% in the downstaging group versus 20.3% and 25.6% in the T2 group (P = 0.04). Kaplan-Meier's 5-year post-transplant survival and recurrence-free probabilities were 77.8% and 90.8%, respectively, in the downstaging group versus 81% and 88%, respectively, in the T2 group (P = 0.69 and P = 0.66, respectively). The 5-year ITT survival was 56.1% in the downstaging group versus 63.3% in the T2 group (P = 0.29). Factors predicting dropout in the downstaging group included pretreatment alpha-fetoprotein ≥1,000 ng/mL (multivariate hazard ratio [HR]: 2.42; P = 0.02) and Child's B versus Child's A cirrhosis (multivariate HR: 2.19; P = 0.04). Successful downstaging of HCC to within T2 criteria was associated with a low rate of HCC recurrence and excellent post-transplant survival, comparable to those meeting T2 criteria without downstaging. Owing to the small number of patients with 4-5 tumors, further investigations are needed to confirm the efficacy of downstaging in this subgroup.

Successful Down-staging of Hepatocellular Carcinoma with Intra-arterial Therapy Prior to Liver Transplantation: A Case Report

Background: Down-staging strategy of Hepatocellular carcinoma (HCC) prior to Liver Transplantation (LT) is important for preventing drop-out from the waiting list for LT or further enlargement of the adaptation of LT. Hepatic arterial infusion chemotherapy with cisplatin in lipiodol and 5-fluorouracil (HAIC with lipiodol) is a novel and effective treatment for advanced HCC. Here we report a successful down-staging case of HCC by a series of therapeutic strategies using HAIC with lipiodol that provided an effective bridge to LT. Case Report: We report a 48-year-old patient with severe liver cirrhosis, a 7.5 cm primary HCC in segment 8 and a 1.2 cm satellite lesion in segment 4, which was outside both Milan Criteria and University of California, San Francisco (UCSF) Criteria. We offered HAIC with lipiodol therapy using a temporary indwelling catheter system with intent to down-stage prior to LT. Six months after initial treatment, complete tumor remission was achieved. However, the patient developed HCC recurrence within the Milan Criteria on further six months later, and LT was performed. Examination of the explant revealed pathologic complete response of both primary and satellite lesions treated by HAIC with lipiodol showed pathologically complete necrosis. This patient is free from recurrence 5 years after LT. Conclusion: HAIC with lipiodol using a temporary indwelling catheter system may be effective to down-stage HCC prior to LT.

Optimal methods for measuring eligibility for liver transplant in hepatocellular carcinoma patients undergoing transarterial chemoembolization

We investigated the optimal radiologic method for measuring hepatocellular carcinoma (HCC) treated by transarterial chemoembolization (TACE) in order to assess suitability for liver transplantation (LT). 271 HCC patients undergoing TACE prior to LT were classified according to both Milan and up-to-seven criteria after TACE by using the enhancement or size method on computed tomography images. The cumulative incidence function curves with competing risks regression was used in post-LT time-to-recurrence analysis. The predictive accuracy for recurrence was compared using area under the time-dependent receiver operating characteristic curves (AUC) estimation. Of the 271 patients, 246 (90.8%) and 164 (60.5%) fell within Milan and 252 (93.0%) and 210 (77.5%) fell within up-to-seven criteria, when assessed by enhancement and size methods, respectively. Competing risks regression analyses adjusting for covariates indicated that meeting the criteria by enhancement and by size methods was independently related to post-LT time-to-recurrence in the Milan or up-to-seven model. Higher AUC values were observed with the size method only in the up-to-seven model (p<0.05). Mean differences in the sum of tumor diameter and number of tumors between pathologic and radiologic findings were significantly less by the enhancement method (p<0.05). Cumulative incidence curves showed similar recurrence results between patients with and without prior TACE within the criteria based on either method, except for the within up-to-seven by the enhancement method (p=0.017). The enhancement method is a reliable tool for assessing the control or downstaging of HCC within Milan after TACE, although the size method may be preferable when applying the up-to-seven criterion.

A Comprehensive Analysis of Downstaging To Meet Listing Criteria For Hepatocellular Carcinoma and Outcome.

Introduction: It is felt that hepatocellular carcinoma (HCC) patients who respond to downstaging with chemoembolization (CE) to Milan criteria have disease recurrence rates similar to those transplanted within Milan and without pre-liver transplant CE. This activity is not without expense. Here we evaluate CE effectiveness in downstaging and assess reimbursements for clinical actions associated or as a consequence of CE. Methods: A single center study of patients receiving CE for downstaging to Milan criteria for listing and transplantation was performed. Patient gender, age and liver primary disease, clinical comorbidities were collected. HCC size and number, downstaging selection criteria, pre and post CE imaging, time to listing, transplant wait time from listing and number of CE procedures was collected. Laboratory values, tumour markers, diagnostic imaging and hospitalizations were monitored Pre and Post CE procedure. Successful downstaging leading to transplant was analyzed and Medicare reimbursement rates used to evaluate reimbursements. Results: A total of 45 patients underwent HCC downstaging with CE between June 2008 and May 2013. 144 CE procedures were performed on the 45 patients (3.2procedures/patient). There was no significant difference in AFP, number of tumors, or tumor size or reimbursements in those successfully downstaged versus not successfully downstaged. The average numbers of imaging studies per patient were: CT Chest 2.5, CT Abdomen 1.8, MRI Abdomen 3.6, and Bone Scan Whole Body 1.6. There were a total of 33 hospitalizations with 5 patients having more than 1 hospitalization. Of these 45 patients, 18 (40%) were successfully downstaged and transplanted. There was no significant difference in age, gender or number of procedures between patients who were transplanted and those who did not meet criteria. The reimbursements associated with successfully downstaging a patient averaged $19986 and number to treat was 2.5. Conclusion: Although some private payers in the United States do not reimburse downstaging, a significant number of patients can be listed by downstaging with CE and transplanted without disease recurrence after transplant. The approximate cost in successfully downstaged patients is $20,000 when hospitalizations are excluded. In an era where medical expenditure comes under greater scrutiny, clinical and economic justification for down staging appears to be present. DISCLOSURES:Gilroy, R.: Speaker's Bureau, Gilead Science, Inc., Salix, Vertex, NPS Pharmaceuticals, Inc.

Safety and Feasibility of Same-Day Discharge of Patients with Hepatocellular Carcinoma Treated with Transarterial Chemoembolization with Drug-Eluting Beads in a Liver Transplantation Program

PurposeTo evaluate the safety and feasibility of same-day discharge of patients with hepatocellular carcinoma (HCC) treated with transarterial chemoembolization with the use of drug-eluting beads (DEBs) and elucidate the prognostic factors for hospital admission. Materials and MethodsA total of 266 DEB chemoembolization procedures in 154 consecutive patients listed for liver transplantation or identified for potential HCC downstaging were performed with the outpatient treatment protocol. Endpoints evaluated were admission to the hospital after the procedure for clinical reasons, readmission to the hospital within 1 month of the procedure, and procedure-related morbidity and mortality. In the evaluation of prognostic factors for admission, parameters of patients discharged the same day were compared with those of patients admitted overnight. ResultsSame-day discharge was feasible in 238 cases (89.5%), and 28 (10.5%) needed overnight admission. The main reason for overnight admission was postprocedural abdominal pain (n = 23; 67.8%). The procedure-related complication rate was 2.6%, and there were no readmissions or deaths during the first 30 days after chemoembolization. Chemoembolization performed for downstaging and the use of more than one vial of embolic agent were associated with an increased need for overnight admission (P = .012 and P = .007, respectively). ConclusionsSame-day discharge of patients with HCC treated with DEB chemoembolization in a liver transplantation program is safe and feasible, with low complication and admission rates. Treatment for HCC downstaging and the use of more than one vial of embolic agent were associated with an increased need for hospital admission.

Down-staging of hepatocellular carcinoma via external-beam radiotherapy with subsequent liver transplantation: A case report

Despite the widespread use of locoregional therapies [radiofrequency ablation and transarterial chemoembolization (TACE)], there is currently a lack of high-quality evidence supporting their use for hepatocellular carcinoma (HCC) in patients on the liver transplantation (LT) waiting list or requiring down-staging. Radiotherapy has rarely been used in this setting and has usually been in the form of more complex and less accessible techniques such as proton-beam and stereotactic body radiation therapy. Only 1 report describes the use of conventional 3-dimensional conformal external-beam radiotherapy (cEBRT) techniques as neoadjuvant or down-staging therapy for patients who are LT candidates. This report describes the use of cEBRT in a 52-year-old hepatitis C-positive man with cirrhosis. A 40-mm right lobe HCC was treated initially with TACE while he was on the waiting list. The lesion progressed beyond transplant criteria (76 mm). Conventional external-beam radiotherapy (EBRT) was used (54 Gy in 27 fractions) to down-stage the lesion. EBRT was well tolerated and resulted in a complete radiological response with no arterial enhancement of the lesion for a total of 16 months. Subsequent LT and a review of the explant demonstrated complete histological necrosis of the lesion. This report provides the first description of complete histological necrosis of HCC through the use of cEBRT techniques as down-staging/neoadjuvant therapy before LT. Because of its potential efficacy, accessibility, tolerability, noninvasive and outpatient nature, and ability to treat lesions adjacent to vessels and biliary structures, further trials examining the efficacy of cEBRT versus other neoadjuvant techniques are urgently required.

Orthotopic liver transplantation after the combined use of locoregional therapy and sorafenib for advanced hepatocellular carcinoma

We herein report a patient with advanced hepatitis B virus-related hepatocellular carcinoma (HCC) beyond the Milan criteria. He underwent orthotopic liver transplantation after successful HCC downstaging that satisfied the University of California, San Francisco criteria, using concurrent chemoradiation therapy with a combination of repeated hepatic arterial infusion chemotherapy (HAIC) and sorafenib. A 52-year-old male was diagnosed with advanced hepatitis B virus-related HCC beyond the Milan criteria. He underwent concurrent chemoradiation therapy (50 Gy with 20 fractions over 5 weeks with HAIC using 5-fluorouracil at a dose of 500 mg/day, which was administered during the first and fifth weeks of radiation therapy) as an initial treatment modality. This was followed by the combined use of HAIC using 5-fluorouracil (500 mg/m2 for 5 hours on days 1–3) and cisplatin (60 mg/m2 for 2 hours on day 2) every 4 weeks (twelve cycles) and sorafenib (from the third to the twelfth cycle of HAIC) to treat the remaining HCC. Because a remarkable decrease in the tumor burden that satisfied the University of California, San Francisco criteria was observed after these combination treatments, the patient underwent orthotopic liver transplantation with curative aim and survived for 11 months without evidence of HCC recurrence.

THU-09 Hepatocellular carcinoma downstaging to transplantation

THU-09 Hepatocellular carcinoma downstaging to transplantation

Does a patient qualify for liver transplantation after the down-staging of hepatocellular carcinoma?

SUMMARY Our review of the literature suggests that uniform cri-teria are needed for future studies investigating fur-ther the efficacy and safety of HCC down-stagingbefore LT. Our recommendations are as follows:1. We define HCC down-staging as reducing the tu-mor size with locoregional therapy specifically tomeet acceptable criteria for LT (grade D).2. The tumor response to down-staging treatmentsshould be based on radiological measurementsof the sizes of viable tumors, and the measure-ment should not include the areas of necrosisresulting from locoregional therapy (grade D).3. We propose a goal of achieving a 5-year post-transplant survival rate of 60% to 70% after tu-mor down-staging. Whether intention-to-treatsurvival rates should be compared for thosemeeting the Milan criteria and those undergoingdown-staging remains a debatable issue(grade D).4. We propose using the Milan criteria as the end-point for down-staging, and more data aboutlong-term outcomes are needed (grade C).5. Well-defined upper limits for the tumor size andnumber should be used to determine the eligibil-ity for down-staging before LT (grade D). Otherfactors to be considered include an upper limitfor the AFP level; beyond this limit, down-stagingtreatments are not likely to be successful, andposttransplant outcomes may be significantlyworse.6. TACE is the most commonly used treatment mo-dality, but there is no evidence that one treat-ment is superior to others in achieving down-staging (grade D). More data on the safety ofdown-staging are needed.7. A minimal observation period of 3 monthsbetween successful down-staging and LT is rec-ommended (grade D).8. We propose the following criteria for treatmentfailure for down-staging: (1) tumor progression toone or more of the endpoints resulting in perma-nent removal from the waiting list (vascular inva-sion, extrahepatic spread, or tumor sizes andnumbers beyond the inclusion criteria), (2) deathdue to any cause before LT, and (3) the recur-rence of HCC after LT (grade D).

Systematic review of outcome of downstaging hepatocellular cancer before liver transplantation in patients outside the Milan criteria

The aim of this systematic review was to assess the evidence on tumour downstaging before liver transplantation in patients with hepatocellular carcinoma (HCC) initially staged beyond the Milan criteria. MEDLINE (from 1952), Embase (from 1980) and the Cochrane Library were searched. The review included cohort studies that reported the outcomes of patients with HCC outside the Milan criteria who underwent downstaging before transplantation. Eight studies met the inclusion criteria and included a total of 720 patients who underwent transplantation following downstaging after initial presentation with disease outside the Milan criteria. The rate of successful downstaging varied from 24 to 69 per cent of patients. Reported survival rates ranged from 82 to 100 per cent, 79 to 100 per cent and 54·6 to 94 per cent at 1, 3 and 5 years respectively. These were comparable with results for patients presenting within the Milan criteria. Successful downstaging of HCC to within the Milan criteria is feasible in a proportion of patients. Absolute and disease-free survival rates in patients transplanted following downstaging are comparable to those in patients within the Milan criteria.

Outcomes of loco-regional therapy for down-staging of hepatocellular carcinoma prior to liver transplantation

The number of loco-regional therapies (LRTs) for hepatocellular carcinoma (HCC) has increased dramatically during the past decade. Many patients with HCC who were beyond the Milan criteria were allowed to receive a liver transplantation (LT) once the HCC was successfully down-staged. This retrospective study aimed to analyze the outcomes of LRTs prior to LT in patients with HCC beyond the Milan criteria. We analyzed 56 patients treated from June 2006 to March 2010: 22 met the Milan criteria (T1+T2, 39.3%), 16 had T3 tumors (28.6%), and 11 had T4a tumors (19.6%), while 7 were suspected of tumor vascular invasion (T4b, 12.5%). All patients underwent preoperative LRTs, including transcatheter arterial chemoembolization, radiofrequency ablation, percutaneous ethanol injection, liver resection, and/or microwave coagulation therapy. The number of the patients who were successfully down-staged before LT, the types of LRTs used before LT, and their outcomes after LT were recorded. Eleven patients had necrotic tumors (pT0, 19.6%); 6 had pT1 tumors (10.7%), 22 had pT2 tumors (39.3%), 6 had pT3 tumors (10.7%), 5 had pT4a tumors (8.9%), and 6 had pT4b tumors (10.7%). The histopathologic tumors of 39 patients (69.6%) were down-staged and met the established Milan criteria (pT0-2). Imaging-proven under-staging was present in 5 HCC patients (8.9%) who had tumors involving the intrahepatic venous system. Twenty-three patients (41.1%) had stable HCC and 10 (17.9%) died. The 1-, 3- and 4-year survival rates were 96%, 73% and 61%, respectively, with a mean survival time of 22.29+/-1.63 months. Six patients died of tumor recurrence. The 1-, 3- and 4-year recurrence-free survival (RFS) rates were 88%, 75% and 66%, respectively. The 3-year RFS of patients with pT0-2 tumors was 82%, which was markedly greater than that of patients with pT3 tumors (63%, P=0.018) or pT4 tumors (17%, P=0.000). Although the 3-year RFS of patients with pT3 tumors was greater than that of patients with pT4 tumors, the difference was not significant. Successful down-staging of HCCs can be achieved in the majority of carefully selected patients by LRTs. Importantly, patients who are successfully down-staged and undergo LT may have a higher RFS rate.

Benefit of downsizing hepatocellular carcinoma in a liver transplant population

Long-term results after downstaging hepatocellular carcinoma (HCC) prior to liver transplantation (LT) remain unknown. To investigate dropouts and post-transplant outcome among patients with downstaged HCC by transarterial chemo-lipiodolization (TACL). Between 2000 and 2007, 386 patients with HCC initially exceeding Milan criteria underwent TACL for tumour downstaging and were consecutively enrolled. Overall, 160 (41.5%) patients achieved successful downstaging of HCC to within Milan criteria. During the follow-up, 82 eventually dropped off the waiting list for LT, with estimated dropout rates at 1, 2 and 5 years of 46.7%, 70.2%, and 87.2%, respectively. The overall post-transplant survival rates at 1, 2 and 5 years were 89.2%, 70.3% and 54.6% and the corresponding rates for recurrence-free survival were 74.7%, 71.8% and 66.3% respectively. Multivariate analysis indentified alpha-fetoprotein (AFP) levels > or = 100 ng/mL at LT (P = 0.003), maximum tumour size > or = 7 cm (P = 0.002) and the lack of complete necrosis by TACL (P = 0.048) as independent predictors of HCC recurrence after LT. Patients with none of these risk factors had an excellent post-transplant outcome, with an 87.5% probability of recurrence-free survival up to 6 years. These long-term results may contribute to the database for optimizing management of LT candidates with downstaged HCC. Based on our data, patients with a maximum tumour size <7 cm who achieve complete necrosis together with AFP levels <100 ng/mL at LT may be the best candidates for LT following downstaging using TACL.

The high‐risk recipient: the Eighth Annual American Society of Transplant Surgeons’ State‐of‐the‐Art Winter Symposium

The evolution of organ transplantation has produced results so successful that many transplant programs commonly see recipients with medical risks, which in the past, would have prohibited transplantation. The Eighth Annual American Society of Transplant Surgeons State-of-the-Art Winter Symposium focused on the high-risk recipient. The assessment of risk has evolved over time, as transplantation has matured. The acceptance of risk associated with a given candidate today is often made in consideration of the relative value of the organ to other candidates, the regulatory environment, and philosophical notions of utility, equity, and fairness. In addition, transplant programs must balance outcomes, transplant volume, and the costs of organ transplantation, which are impacted by high-risk recipients. Discussion focused on various types of high-risk recipients, such as those with coronary artery disease, morbid obesity, and hepatitis C; strategies to reduce risk, such as down-staging of hepatocellular carcinoma and treatment of pulmonary hypertension; the development of alternatives to transplantation; and the degree to which risk can or should be used to define candidate selection. These approaches can modify the impact of recipient risk on transplant outcomes and permit transplantation to be applied successfully to a greater variety of patients.