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HCC Recurrence (hcc + recurrence)

Distribution by Scientific Domains

Medical Sciences	86%

Distribution within Medical Sciences

Transplantation	65%
Hepatology	19%
Gastroenterology & Hepatology	15%

Selected Abstracts

Excellent outcome following down-staging of hepatocellular carcinoma prior to liver transplantation: An intention-to-treat analysis,,

HEPATOLOGY, Issue 3 2008
Francis Y. Yao
We previously reported encouraging results of down-staging of hepatocellular carcinoma (HCC) to meet conventional T2 criteria (one lesion 2,5 cm or two to three lesions <3 cm) for orthotopic liver transplantation (OLT) in 30 patients as a test of concept. In this ongoing prospective study, we analyzed longer-term outcome data on HCC down-staging in a larger cohort of 61 patients with tumor stage exceeding T2 criteria who were enrolled between June 2002 and January 2007. Eligibility criteria for down-staging included: (1) one lesion >5 cm and up to 8 cm; (2) two to three lesions with at least one lesion >3 cm and not exceeding 5 cm, with total tumor diameter up to 8 cm; or (3) four to five lesions with none >3 cm, with total tumor diameter up to 8 cm. A minimum observation period of 3 months after down-staging was required before OLT. Tumor down-staging was successful in 43 patients (70.5%). Thirty-five patients (57.4%) had received OLT, including two who had undergone live-donor liver transplantation. Treatment failure was observed in 18 patients (29.5%), primarily due to tumor progression. In the explant of 35 patients who underwent OLT, 13 had complete tumor necrosis, 17 met T2 criteria, and five exceeded T2 criteria. The Kaplan-Meier intention-to-treat survival at 1 and 4 years after down-staging were 87.5% and 69.3%, respectively. The 1-year and 4-year posttransplantation survival rates were 96.2% and 92.1%, respectively. No patient had HCC recurrence after a median posttransplantation follow-up of 25 months. The only factor predicting treatment failure was pretreatment alpha-fetoprotein >1,000 ng/mL. Conclusion: Successful down-staging of HCC can be achieved in the majority of carefully selected patients and is associated with excellent posttransplantation outcome. (HEPATOLOGY 2008.) [source]

Expression of X-linked inhibitor-of-apoptosis protein in hepatocellular carcinoma promotes metastasis and tumor recurrence,

HEPATOLOGY, Issue 2 2008
Ying-Hong Shi
Hepatocellular carcinoma (HCC) is one of the most common malignant tumors worldwide. Despite significantly improved diagnosis and treatment in recent years, the long-term therapeutic effect is compromised by the frequent recurrence and metastasis, of which the molecular mechanisms are not fully understood. Our initial studies in established HCC cell lines with different metastatic capabilities indicated a correlation of metastasis with the resistance to apoptosis and therefore the ability to survive in stressed conditions. Subsequent investigation revealed that increased expression of X-linked inhibitor-of-apoptosis protein (XIAP) was correlated with the resistance to apoptosis and enhanced invasiveness in vitro, which could contribute to increased metastatic foci in vivo. Furthermore, we found that nearly 90% of clinical samples from advanced HCC patients expressed high levels of XIAP. Patients with XIAP-positive tumors had a significantly increased risk of relapse, which resulted from metastasis after total liver resection and orthotopic liver transplantation. Indeed, XIAP expression could be an independent prognostic factor for predicting disease-free survival rate and overall survival rate of these patients. XIAP expression was also highly correlated with advanced cases that exceeded the Milan criteria and could be a prognostic factor for disease-free survival in these patients as well. Conclusion: Our studies have shown an important molecule in controlling HCC metastasis, defined a biomarker that can be used to predict HCC recurrence and patient survival after treatment, and suggest that XIAP can be a molecular target subject to intervention to reduce metastasis and recurrence. (HEPATOLOGY 2008;48:497,507.) [source]

Prevention of hepatocellular carcinoma recurrence with alpha-interferon after liver resection in HCV cirrhosis,,§

HEPATOLOGY, Issue 6 2006
Vincenzo Mazzaferro
Tumor recurrence after resection of hepatocellular carcinoma (HCC) can occur early (<2 years) or late (>2 years) as metastases or de novo tumors. Interferon (IFN) has the potential for chemoprevention against hepatitis C virus (HCV)-related cirrhosis. A predetermined group of 150 HCV RNA,positive patients undergoing resection of early- to intermediate-stage HCC was stratified into 80 HCV-pure (hepatitis B anticore antibody [anti-HBc],negative) and 70 mixed HCV+hepatitis B virus (HBV) (anti-HBc,positive) groups, then randomized to IFN-, (3 million units 3 times every week for 48 weeks [n = 76]) versus control (n = 74). The primary end point was recurrence-free survival (RFS); secondary end points were disease-specific and overall survival. Intention-to-treat and subgroup analysis on adherent patients were conducted. Treatment effects on early/late recurrences were assessed using multiple Cox regression analysis. No patient experienced life-threatening adverse events. There were 28 adherent patients (37%). After 45 months of median follow-up, overall survival was 58.5%, and no significant difference in RFS was detectable between the two study arms (24.3% vs. 5.8%; P = .49). HCC recurred in 100 patients (48 IFN-treated, 52 controls), with a 50% reduction in late recurrence rate in the treatment arm. HCC multiplicity and vascular invasion were significantly related to recurrence (P = .01 and .0003). After viral status stratification, while no treatment effect was apparent in the mixed HCV+HBV population and on early recurrences (72 events), there was a significant benefit on late recurrences (28 events) in HCV-pure patients adherent to treatment (HR: 0.3; 95% CI: 0.09,0.9; P = .04). In conclusion, IFN does not affect overall prevention of HCC recurrence after resection, but it may reduce late recurrence in HCV-pure patients receiving effective treatment. (HEPATOLOGY 2006;44:1543,1554.) [source]

Role of additional angiography and chemoembolization in patients with hepatocellular carcinoma who achieved complete necrosis following transarterial chemoembolization

JOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY, Issue 9 2004
MYOUNG KUK JANG
Abstract Background and Aims:, Although transarterial chemoembolization (TACE) has been reported to have antitumor effects in patients with hepatocellular carcinoma (HCC), optimal time schedules and follow-up methods have not yet been determined. We therefore prospectively analyzed the effects of additional angiography and chemoembolization on HCC recurrence and survival in patients who underwent TACE and achieved complete necrosis (CN). Methods:, A total of 68 patients who achieved CN after TACE, as assessed using dynamic computed tomography (CT), were randomized into two groups. Patients in the CT group (n = 34) were followed using dynamic CT every 3 months without any further intervention, whereas patients in the angiography group (n = 34) received additional angiography 1 month after achievement of CN. We compared overall survival and disease-free survival between the two groups and analyzed the benefit of additional angiography. Results:, The cumulative recurrence rate did not differ between the angiography and CT groups (55%vs 48% at 12 months and 66%vs 67% at 24 months, P = 0.92). The overall survival rates at 12 and 24 months were 88% and 84% in the angiography group, and 88% and 70% in the CT group, respectively (P = 0.57). Of the 34 patients in the angiography group, 27 (79%) suffered from adverse reactions of additional angiography and subsequent chemoembolization, seven (20.6%) experienced serum bilirubin increases of ,1 mg/dL over baseline, and two (5.9%) developed renal impairment. Conclusion:, Additional angiography and chemoembolization did not reduce tumor recurrence or improve patient survival in HCC patients who achieved CN, as assessed using dynamic CT, following TACE. © 2004 Blackwell Publishing Asia Pty Ltd [source]

Role of long-term lamivudine treatment of hepatitis B virus recurrence after liver transplantation

JOURNAL OF MEDICAL VIROLOGY, Issue 11 2008
Hyun Young Woo
Abstract In this study, the long-term (>3 years) efficacy of combination therapy for hepatitis B virus (HBV) recurrence and the associated factors were investigated. One hundred and sixty-five consecutive HBsAg-positive patients (92 with liver cirrhosis, 73 with hepatocellular carcinoma; HCC) who underwent liver transplantation were assessed with a median follow-up time of 40 months. One hundred and twenty-one patients (121/165, 73.3%) were treated with lamivudine before transplantation for a mean of 8.4 months (range 0.1,72 months). The post-transplantation treatment protocol consisted of a high dose intravenous hepatitis B immunoglobulin (HBIg) followed by a low dose intramuscular HBIg and lamivudine combination therapy. Seven (4.2%, 7/165) recipients experienced HBV recurrence at a median time of 19 months (range 5,36 months) following transplantation. Six of seven cases of HBV recurrence were treated with lamivudine before transplantation for a median period of 15 months (range 0.6,30 months). Eighteen (24.6%, 18/73) patients had HCC recurrences after transplantation. Of the four patients with both HCC and HBV recurrence, three experienced HBV recurrence after recurrence of HCC. The clinical factor associated with HBV recurrence in the total cohort (n,=,165) was the duration of antiviral treatment (over 6 months) before transplantation (P,=,0.004). In the HCC group, HCC recurrence after transplantation (P,=,0.002), tumor burden before transplantation (P,=,0.005), and postoperative adjuvant chemotherapy (P,=,0.002), were additional factors for HBV recurrence. Combination therapy of HBIg and antiviral drugs was effective over 3 years regardless of the pretransplantation viral load. However, the possible recurrence of HBV needs to be monitored cautiously in patients treated with long-term (over 6 months) lamivudine. J. Med. Virol. 80:1891,1899, 2008. © 2008 Wiley-Liss, Inc. [source]

Role of hepatitis B virus genotypes and quantitative HBV DNA in metastasis and recurrence of hepatocellular carcinoma

JOURNAL OF MEDICAL VIROLOGY, Issue 4 2008
Yuehua Huang
Abstract Identification of risk factors for recurrence and metastasis of HCC is important for the prognosis of HCC surveillance in chronic HBV infection. In this article, 125 HCC patients recruited were followed up prospectively for tumor metastasis and recurrence for a median of 104 (10,130) weeks. HBV DNA level was detected by LightCycler-based real-time fluorescence quantitative polymerase chain reaction-restriction system. HBV genotypes were determined by using PCR restriction-fragment length polymorphism. BCP and PC mutations were performed by PCR and direct sequencing of amplified products. Among 125 HCC patients, 19 patients were excluded because of the lack of follow-up data and the remaining 106 patients were followed up of 2 years and entered into analysis. Sixty-nine patients had tumor metastasis or recurrence during the follow-up and the cumulative probability of HCC metastasis or recurrence was 65.1%. On multivariate analysis, genotype C and HBV DNA level were the risk factors for HCC recurrence or metastasis. The incidence of recurrence or metastasis increased with baseline HBV DNA level in a dose-response relationship ranging from 22% for HBV DNA level of less than 3 log10 copies/ml to 80% for HBV DNA level of 5 log10 copies/ml or greater (P,=,0.012). Fifty-seven (74.0%) and 12 (41.4%) patients had metastasis or recurrence in patients with genotype C and B, respectively. The adjusted OR of recurrence or metastasis for genotype C compared with genotype B was 9.755 (P,=,0.009). In conclusion, elevated HBV DNA level and genotype C are strong risk predictors of HCC metastasis or recurrence. J. Med. Virol. 80:591,597, 2008. © 2008 Wiley-Liss, Inc. [source]

Meta-analysis: interferon improves outcomes following ablation or resection of hepatocellular carcinoma

ALIMENTARY PHARMACOLOGY & THERAPEUTICS, Issue 7 2010
A. K. Singal
Aliment Pharmacol Ther 2010; 32: 851,858 Summary Background, Hepatocellular carcinoma (HCC) is third most common cause of tumour-related death in the US with hepatitis C virus (HCV) the most common aetiology. Surgical resection and tumour ablation are curative in patients who cannot be transplanted. With native liver having cirrhosis, HCC recurrence is a potential problem. Aim, To perform a systematic review and meta-analysis of studies evaluating efficacy of IFN to prevent HCC recurrence after its curative treatment in HCV-related cirrhosis. Methods, Ten studies (n = 645, 301 treated with IFN) on the use of IFN after resection or ablation of HCV-associated HCC were analysed. Results, Pooled data showed benefit of IFN for HCC prevention with OR (95% CI) of 0.26 (0.15,0.45); P < 0.00001. The proportion of patients surviving at 5 years (n = 505 in 6 studies) was in favour of IFN with OR of 0.31 [(95% CI 0.21,0.46); P < 0.00001]. Data were homogeneous for HCC recurrence (,2 12.05, P = 0.21) and survival (,2 6.93, P = 0.44). The benefit of IFN was stronger with sustained virological response compared with nonresponders for HCC recurrence [0.19 (0.06,0.60); P = 0.005] and survival [0.31 (0.11,0.90); P = 0.03]. Conclusion, Interferon treatment after curative resection or ablation of HCC in HCV-related cirrhotics prevents HCC recurrence and improves survival. [source]

Benefit of downsizing hepatocellular carcinoma in a liver transplant population

ALIMENTARY PHARMACOLOGY & THERAPEUTICS, Issue 3 2010
J. W. JANG
Aliment Pharmacol Ther,31, 415,423 Summary Background, Long-term results after downstaging hepatocellular carcinoma (HCC) prior to liver transplantation (LT) remain unknown. Aims, To investigate dropouts and post-transplant outcome among patients with downstaged HCC by transarterial chemo-lipiodolization (TACL). Methods, Between 2000 and 2007, 386 patients with HCC initially exceeding Milan criteria underwent TACL for tumour downstaging and were consecutively enrolled. Results, 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 ,100 ng/mL at LT (P = 0.003), maximum tumour size ,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. Conclusions, 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. [source]

Living donor liver transplantation in hepatocellular carcinoma beyond the Milan criteria

LIVER INTERNATIONAL, Issue 8 2008
Hyun Young Woo
Abstract Background/Aims: In patients with hepatocellular carcinoma (HCC) exceeding the Milan criteria, the recurrence rate after liver transplantation is over 50%. We investigated pretransplant factor(s) that could predict recurrence after living donor liver transplantation (LDLT) in patients with HCC exceeding the Milan criteria. Methods: Pre-operative imaging showed that, of the 111 HCC patients who underwent LDLT between June 1995 and January 2006, 37 exceeded the Milan criteria. Clinical factors before LDLT were evaluated. Results: The 1- and 3-year cumulative recurrence rates were 35 and 55% respectively. Pretransplant risk factors for HCC recurrence were large tumour size (>6 cm, P=0.001), tumour exposed to the liver surface (P=0.014) and progressive disease after pretransplant treatment (P=0.038). The 2-year HCC recurrence rates in patients with 0, 1, 2 and 3 factors were 0% (0/4), 9% (1/16), 80% (8/10) and 100% (7/7) respectively (P<0.001). The 2-year survival rate was significantly higher in patients with 0 or 1 factor than in patients with two or more factors (P=0.022). Conclusions: In patients with HCC exceeding the Milan criteria, the three pretransplant factors that may be useful for identifying those with high HCC recurrence potential after LDLT are tumour size >6 cm, progressive disease after pretransplant treatment and tumour exposed to the liver surface. [source]

Usefulness 18F-FDG positron emission tomography/computed tomography for detecting recurrence of hepatocellular carcinoma in posttransplant patients

LIVER TRANSPLANTATION, Issue 6 2010
Young-Kyu Kim
18F-fluoro-2-deoxy-D-glucose (18F-FDG) positron emission tomography (PET)/computed tomography (CT) has recently been shown to be able to predict a poor outcome after liver transplantation (LT) for patients with hepatocellular carcinoma (HCC). However, there are few reports on the usefulness of PET during follow-up after LT. In this study, we assessed the efficacy of 18F-FDG PET/CT for the detection of HCC recurrence after LT. From February 2005 to December 2008, out of 93 adult LT cases (91 living donors and 2 deceased donors), 10 patients who showed HCC recurrence and received 18F-FDG PET/CT during follow-up were included. The accuracy of 18F-FDG PET/CT was assessed with imaging and histological studies. The most common sites of recurrence were extrahepatic (60%). The most common extrahepatic sites were the lungs and bone (31.3% each). Among 4 patients with intrahepatic recurrence, 1 patient (25%) was positive according to 18F-FDG PET/CT. The detection rate of 18F-FDG PET/CT was 92.9% for extrahepatic metastases , 1 cm and 0% for lesions < 1 cm. The detection rate of 18F-FDG PET/CT was 100% in bone and the lymph nodes, 60% in the lungs, and 0% in the brain. 18F-FDG PET/CT identified 2 lesions in bone that were not found in a bone scan. In conclusion, because of its limitations for small lesions, intrahepatic lesions, and brain lesions, 18F-FDG PET/CT is not suitable as a screening tool after LT. However, 18F-FDG PET/CT could provide additional information beyond that provided by conventional modalities, and it could contribute to the clinical management of HCC recurrence after LT, especially in patients with extrahepatic recurrence. Liver Transpl 16:767-772, 2010. © 2010 AASLD. [source]

Expression of matrix metalloproteinase-9 in predicting prognosis of hepatocellular carcinoma after liver transplantation

LIVER TRANSPLANTATION, Issue 5 2010
Deniz Nart
Matrix metalloproteinases (MMPs) are known to play an important role in cell migration during cancer invasion by degrading extracellular matrix proteins. This study aimed to determine the role of MMP-9 in hepatocellular carcinoma (HCC) carcinogenesis. Eighty-nine cases who underwent liver transplantation for HCC in cirrhotic liver were selected for this study. The tumor characteristics such as nodule number, maximal diameter, portal vein invasion, and the preoperative alpha-fetoprotein levels were reviewed. The intensity of immunostaining and the percentage of immunoreactive cells with MMP-9 were evaluated. All patients were evaluated for HCC recurrence and/or death, and cause of death was noted. There was a lower survival and more recurrence risk among participants with 4 or more nodules exceeding 3 cm in diameter, with poorly differentiated tumor, and with large-vessel involvement. Eleven patients developed recurrent HCC (12.4%). Twelve patients died as a result of HCC (13.5%). Among 89 HCCs, the incidences of a weak (+) and moderate (++) expression of MMP-9 in carcinoma cells were 30.3% (23/89) and 43.8% (39/89), respectively. Increased expression and intensity of MMP-9 were found to be inversely associated with poor tumor differentiation (P = 0.016, P = 0.009, respectively). A significant correlation between expression and intensity of MMP-9 and large vascular invasion (P = 0.01, and P = 0.03) was also observed. As far as prognosis is concerned, increased immunoreactivity and intensity of MMP-9 were found to exert an unfavorable impact on overall survival rates (P < 0.01, P = 0.01, respectively) and recurrences (P = 0.001, P = 0.02). Multivariate analyses revealed that MMP-9 staining percentage (P = 0.007) and portal vein invasion (P = 0.002) were independent predictors of survival, whereas the only independent predictor of recurrences was portal vein invasion (P = 0.007). In this study, our results indicate a positive association between MMP-9 expression and histopathologic parameters that indicate poor prognosis. We conclude that together, MMP-9 staining percentage and portal vein invasion in HCC may aid to predict poor outcome. Nevertheless MMP-9 staining percentage is expected to be a potential predictive marker on survival and needs to be studied more in detail. Liver Transpl 16:621-630, 2010. © 2010 AASLD. [source]

Recurrence of hepatocellular carcinoma and hepatitis B reinfection in hepatitis B surface antigen,positive patients after liver transplantation

LIVER TRANSPLANTATION, Issue 11 2009
Sammy Saab
Hepatitis B virus (HBV) reinfection and recurrence of hepatocellular carcinoma (HCC) after orthotopic liver transplantation (OLT) are associated with increased graft failure and reduced patient survival. We evaluated the effects of both HCC recurrence and HBV reinfection on the long-term survival of these patients after OLT. One hundred seventy-five patients underwent OLT for HBV-related liver diseases and were the subjects of this retrospective study. We assessed risk factors for HBV reinfection, HCC recurrence, and survival post-OLT using univariate and multivariate analyses. During a mean follow-up of 43.0 ± 42.0 months, 88 of 175 (50.3%) patients transplanted for HBV-related liver disease had HCC prior to OLT. Thirteen (14.8%) of these patients had HCC recurrence after OLT. The mean time for recurrence of HCC was 26.1 ± 31.9 months. Twelve of 175 (6.9%) patients developed HBV reinfection after liver transplantation. The mean time for HBV reinfection was 28.7 ± 26.4 months. Ten of these 12 (83.3%) patients had HCC prior to OLT, and 5 (50%) developed recurrence of HCC. On multivariate analyses, pre-OLT HCC and recurrence of HCC post-OLT were significantly associated with HBV reinfection after transplantation (P = 0.031 and P < 0.001, respectively). HCC recurrence after OLT was associated with lymphovascular invasion (P < 0.001) and post-OLT chemotherapy (P , 0.001). The 3- and 5-year survival rates were significantly decreased in patients with HBV reinfection (P = 0.007) and in patients with HCC recurrence after OLT (P = 0.03). In conclusion, pre-OLT HCC and HCC recurrence after transplantation were associated with HBV reinfection and with decreased patient survival. Hepatitis B immunoglobulin and antiviral therapy was only partially effective in preventing HBV reinfection in patients with HCC recurrence. Liver Transpl 15:1525,1534, 2009. © 2009 AASLD. [source]

Identifying risk for recurrent hepatocellular carcinoma after liver transplantation: Implications for surveillance studies and new adjuvant therapies

LIVER TRANSPLANTATION, Issue 7 2008
Edie Y. Chan
The recurrence of hepatocellular carcinoma (HCC) is a major cause of mortality for patients transplanted with HCC. There currently exists no standard method for identifying those patients with a high risk for recurrence. Identification of factors leading to recurrence is necessary to develop an efficient surveillance protocol and address new potential adjuvant therapies. We conducted a retrospective review of 834 consecutive liver transplants from 1/1/1996 to 12/31/2005 (mean follow-up 1303 ± 1069 days) at one institution and 352 consecutive transplants from 1/2/2002 to 12/31/2005 (mean follow-up 836 ± 402 days) at a second institution. The test cohort comprised patients identified with HCC in their explanted livers from 1/1/2001 to 12/31/2005 at the first institution. Explant pathology and donor and recipient characteristics were reviewed to determine factors associated with HCC recurrence. These predictors were validated in the remaining liver transplant recipients. The test cohort had 116 patients with findings of HCC in their explanted livers. Twelve patients developed recurrent HCC. Stepwise logistic regression identified 4 independent significant explant factors predictive of recurrence. Size of one tumor (>4.5 cm), macroinvasion, and bilobar tumor were positive predictors of recurrence, whereas the presence of only well-differentiated HCC was a negative predictor. Designating each significant factor with points in relation to its odds ratio, a Predicting Cancer Recurrence Score (PCRS) with results ranging from ,3 to 6 was developed that accurately determined risk of recurrence. These findings were then applied to the two validation cohorts, which confirmed the high predictive value of this model. In conclusion, patients transplanted for HCC with a PCRS of ,0 have a low risk of recurrence. Patients with a PCRS of 1 or 2 have a moderate risk of recurrence, and those with a PCRS of ,3 have a high risk for recurrence. Liver Transpl 14:956,965, 2008. © 2008 AASLD. [source]

Fractional allelic imbalance could allow for the development of an equitable transplant selection policy for patients with hepatocellular carcinoma

LIVER TRANSPLANTATION, Issue 4 2008
Igor Dvorchik
Liver transplantation (LT) in the presence of hepatocellular carcinoma (HCC) remains a controversial issue because the current staging systems are not sufficiently predictive of outcomes. Paraffin blocks from 183 patients that underwent LT in the presence of HCC were collected. Molecular analysis was carried out blindly on the native liver specimens in all cases with respect to recurrence outcomes. The fractional allelic imbalance (FAI) rate index was determined in each case and was used to compare the acquired mutational load between different tumors. The FAI was determined from the microdissected tissue site displaying the greatest amount of acquired allelic loss. FAI was found to be the strongest predictor of recurrence followed by vascular invasion and then by tumor number or hepatic lobar involvement. Based on these findings, 3 prognostic models were constructed for selection of candidates for LT in patients with concomitant HCC. Molecular markers of tumor progression are the strongest predictors of HCC recurrence currently available, surpassing all components of the tumor-node-metastasis classification system for staging of malignant tumors (TNM), including vascular invasion. Incorporation of these molecular markers of tumor progression could help resolve the ongoing conundrum of organ allocation for patients with HCC. Liver Transpl 2007. © 2007 AASLD. [source]

Comparison of two techniques of transarterial chemoembolization before liver transplantation for hepatocellular carcinoma: A case-control study

LIVER TRANSPLANTATION, Issue 5 2007
Sébastien Dharancy
Supraselective transarterial chemoembolization (STACE) more efficiently targets chemotherapy delivered via the feeding arterial branches of the tumor than does conventional transarterial chemoembolization (TACE). However, the hypothesis of its greater efficacy compared with the latter is subject to controversy. The aim of the present study was to compare STACE to conventional TACE in a controlled study of candidates for liver transplantation (LT) for hepatocellular carcinoma (HCC). Patients were matched for factors associated with HCC recurrence and survival. Sixty patients were included: 30 who were treated with STACE and 30 treated with conventional TACE. The 2 groups were similar in terms of matched criteria. In the overall population (uni- and multinodular HCC), there was no marked difference between the 2 groups in 5-year disease-free survival: 76.8% vs. 74.8%. In sensitivity analysis of patients considered to be the best candidates for TACE (uninodular HCC ,5 cm), there was a trend toward significance between STACE and TACE in 5-year disease-free survival: 87% vs. 64% (P = 0.09). The only factor associated with complete tumor necrosis was STACE in the overall population (30.8% vs. 6.9%, P = 0.02), with a similar trend in the subgroup of patients with a single nodule (33.3% vs. 6.7%, P = 0.06), whereas the mean number of procedures was similar in the 2 groups (mean, 1.3 procedures; range 1-5 procedures; P = NS). STACE is more efficient at inducing complete tumor necrosis in the liver. This study observed trends toward improvement in the disease-free survival of patients with uninodular HCC ,5 cm. Future studies focusing on such patients are warranted. Liver Transpl, 2007. © 2007 AASLD. [source]

A prospective study on downstaging of hepatocellular carcinoma prior to liver transplantation,

LIVER TRANSPLANTATION, Issue 12 2005
Francis Y. Yao
In patients with hepatocellular carcinoma (HCC) exceeding conventional (T2) criteria for orthotopic liver transplantation (OLT), the feasibility and outcome following loco-regional therapy intended for tumor downstaging to meet T2 criteria for OLT are unknown. In this first prospective study on downstaging of HCC prior to OLT, the eligibility criteria for enrollment into a downstaging protocol included 1 lesion >5 cm and ,8 cm, 2 or 3 lesions at least 1 >3 cm but ,5 cm with total tumor diameter of ,8 cm, or 4 or 5 nodules all ,3 cm with total tumor diameter ,8 cm. Patients were eligible for living-donor liver transplantation (LDLT) if tumors were downstaged to within proposed University of California, San Francisco (UCSF) criteria.13 A minimum follow-up period of 3 months after downstaging was required before cadaveric OLT or LDLT, with imaging studies meeting criteria for successful downstaging. Among the 30 patients enrolled, 21 (70%) met criteria for successful downstaging, including 16 (53%) who had subsequently received OLT (2 with LDLT), and 9 patients (30%) were classified as treatment failures. In the explant of 16 patients who underwent OLT, 7 had complete tumor necrosis, 7 met T2 criteria, but 2 exceeded T2 criteria. No HCC recurrence was observed after a median follow-up of 16 months after OLT. The Kaplan-Meier intention-to-treat survival was 89.3 and 81.8% at 1 and 2 yr, respectively. In conclusion, successful tumor downstaging can be achieved in the majority of carefully selected patients, but longer follow-up is needed to further access the risk of HCC recurrence after OLT. (Liver Transpl 2005;11:1505,1514.) [source]

Percutaneous ablation procedures in cirrhotic patients with hepatocellular carcinoma submitted to liver transplantation: Assessment of efficacy at explant analysis and of safety for tumor recurrence

LIVER TRANSPLANTATION, Issue 9 2005
Maurizio Pompili
Aims of this retrospective study were to analyze the efficacy and safety of percutaneous ethanol injection (PEI) and radiofrequency ablation (RFA) in cirrhotic patients with hepatocellular carcinoma (HCC) submitted to orthotopic liver transplantation (OLT). We studied 40 patients undergoing OLT in whom 46 HCC nodules had been treated with PEI (13 nodules), RFA (30 nodules), or PEI+RFA (3 nodules). Child-Turcotte-Pugh class was A in 18 cases, B in 18, and C in 4. The mean waiting time for OLT was 9.5 months. The effectiveness of ablation techniques was evaluated by histological examination of the explanted livers. Complete necrosis was found in 19 nodules (41.3%), partial or absent necrosis in 27 nodules (58.7%). Among the 30 nodules treated by RFA, 14 were completely necrotic (46.7%) and 16 demonstrated partial necrosis (53.3%). Considering the 13 neoplasms undergoing PEI, 3 nodules showed complete necrosis (23.1%), 6 partial necrosis (46.1%), and 4 absent necrosis (30.8%). The rate of complete necrosis was 53.1% for nodules smaller than 3 cm and 14.3% for larger lesions (P = 0.033) but increased to 61.9% when considering only the lesions smaller than 3 cm treated by RFA. During the follow up, HCC recurred in 3 patients treated by PEI. No cases of HCC recurrence at the abdominal wall level were recorded. Percutaneous ablation procedures are effective treatments in cirrhotic patients with HCC submitted to OLT and are not associated to an increased risk of tumor recurrence. RFA provides complete necrosis in most nodules smaller than 3 cm, and appears to be the best treatment option in these cases. (Liver Transpl 2005;11:1117,1126.) [source]

Apparent Remission of a Solitary Metastatic Pulmonary Lesion in a Liver Transplant Recipient Treated with Sorafenib

AMERICAN JOURNAL OF TRANSPLANTATION, Issue 12 2009
M. Yeganeh
Hepatocellular carcinoma (HCC) remains a significant disease worldwide and its incidence is expected to increase. In selected patients, liver transplantation offers a 5-year patient survival between 48% and 75%. However, HCC recurrence occurs in approximately 20% of transplant recipients. No therapy has proven efficacious in decreasing the risk of recurrence after transplantation. Sorafenib, a multitargeted tyrosine kinase inhibitor, has been shown to improve survival in patients with advanced HCC that have no history of liver transplantation. We report complete remission of HCC in a 54-year-old man who developed biopsy-proven lung metastasis after liver transplantation treated with sorafenib. [source]

Significance of Des-Gamma-Carboxy Prothrombin in Selection Criteria for Living Donor Liver Transplantation for Hepatocellular Carcinoma

AMERICAN JOURNAL OF TRANSPLANTATION, Issue 10 2009
M. Fujiki
Des-gamma-carboxy prothrombin (DCP) levels reportedly correlate with histological features of hepatocellular carcinoma (HCC). We examined serum DCP as a predictor of HCC recurrence in 144 patients who underwent living donor liver transplantation. Receiver operating characteristics (ROC) analysis revealed superiority of DCP and AFP over preoperative tumor size or number for predicting recurrence. Multivariate analysis revealed tumor size >5 cm, ,11 nodules, and DCP >400 mAU/mL as significant independent risk factors for recurrence. Incidence of microvascular invasion (62% vs. 27%, p = 0.0003) and poor differentiation (38% vs. 16%, p = 0.0087) were significantly higher for patients with DCP >400 mAU/mL than for patients with DCP ,400 mAU/mL. In ROC analysis for patients with ,10 nodules all ,5 cm to predict recurrence, area under the curve was much higher for DCP than for AFP (0.84 vs. 0.69). Kyoto criteria were thus defined as ,10 nodules all ,5 cm, and DCP ,400 mAU/mL. The 5-year recurrence rate for 28 patients beyond-Milan but within-Kyoto criteria was as excellent as that for 78 patients within-Milan criteria (3% vs. 7%). The preoperative DCP level offers additional information regarding histological features, and thus can greatly improve patient selection criteria when used with tumor bulk information. [source]

Liver Transplantation for Recurrent Hepatocellular Carcinoma on Cirrhosis After Liver Resection: University of Bologna Experience

AMERICAN JOURNAL OF TRANSPLANTATION, Issue 6 2008
M. Del Gaudio
Liver resection (LR) for patients with small hepatocellular carcinoma (HCC) with preserved liver function, employing liver transplantation (LT) as a salvage procedure (SLT) in the event of HCC recurrence, is a debated strategy. From 1996 to 2005, we treated 227 cirrhotic patients with HCC transplantable: 80 LRs and 147 LTs of 293 listed for transplantation. Among 80 patients eligible for transplantation who underwent LR, 39 (49%) developed HCC recurrence and 12/39 (31%) of these patients presented HCC recurrence outside Milan criteria. Only 10 of the 39 patients underwent LT, a transplantation rate of 26% of patients with HCC recurrence. According to intention-to-treat analysis of transplantable HCC patients who underwent LR (n = 80), compared to all those listed for transplantation (n = 293), 5-year overall survival was 66% in the LR group versus 58% in patients listed for LT, respectively (p = NS); 5-year disease-free survival was 41% in the LR group versus 54% in patients listed for LT (p = NS). Comparable 5-year overall (62% vs. 73%, p = NS) and disease-free (48% vs. 71%, p = NS) survival rates were obtained for SLT and primary LT for HCC, respectively. LR is a valid treatment for small HCC and in the event of recurrence, SLT is a safe and effective procedure. [source]

Treatment of HCC in Patients Awaiting Liver Transplantation

AMERICAN JOURNAL OF TRANSPLANTATION, Issue 8 2007
M. Schwartz
Liver transplantation (LT) is the treatment of choice for many patients with unresectable hepatocellular carcinoma (HCC), but long waiting time due to the shortage of donor organs can result in tumor progression and drop-out from LT candidacy. Furthermore, even in candidates meeting the restrictive Milan criteria there is risk of HCC recurrence; this risk rises significantly when patients with more advanced HCC are included. In an effort to address these issues, treatment of HCC in patients awaiting LT has become widespread practice. In this review the various modalities employed in the pre-LT setting are presented, and the evidence for benefit with regard to (1) improvement of post-LT survival, (2) down-staging of advanced HCC to within Milan criteria and (3) preventing waiting list drop-out is considered. Chemoembolization, radiofrequency ablation and ethanol injection all have well-documented antitumor activity; however, there is no high level evidence that waiting list HCC treatment with these modalities is effective in achieving any of the three above-mentioned aims. Nevertheless, particularly in the United States, where continued waiting list priority depends on maintaining HCC within Milan criteria, use of nonsurgical HCC treatment will likely continue in an effort to forestall tumor progression and waiting list drop-out. [source]