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Milan Criteria (milan + criterion)
Selected AbstractsCurrent controversies surrounding liver transplantation for hepatocellular carcinomaJOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY, Issue 7 2010Mauricio F Silva Abstract Liver transplantation (LT) for hepatocellular carcinoma (HCC) has progressed rapidly over the last decade from a futile therapy to the first choice therapy for suitable patients. Excellent outcomes of LT for HCC can be largely attributed to the use of the Milan Criteria, which have restricted LT to patients with early stage tumors. These criteria may be conservative, and it is likely that a subset of patients with tumors beyond these criteria can have acceptable outcomes. However, there is currently insufficient data to accept more liberal criteria as a standard of care, and a higher quality evidence base must be achieved to prevent poor utilization of valuable donor liver resources. In the future, it is probable that more sophisticated selection criteria will emerge incorporating aspects of tumor biology beyond tumor size and number. Dropout from the waiting list due to tumor progression remains a clinical challenge particularly in regions with prolonged waiting times. Priority allocation using HCC MELD points is a practical and transparent solution that has successfully reduced waitlist dropout for HCC patients. Further refinements of the HCC MELD point system are required to ensure equity of access to LT for non-HCC patients and prioritization of HCC patients with the highest risk of dropout. Improving the evidence base for pre-LT locoregional therapy to prevent waitlist dropout is an urgent and difficult challenge for the LT community. In the interim transplant clinicians must restrict the use of these therapies to those patients who are most likely to benefit from them. [source] An Early Regional Experience with Expansion of Milan Criteria for Liver Transplant RecipientsAMERICAN JOURNAL OF TRANSPLANTATION, Issue 9 2010J. J. Guiteau The Milan Criteria (MC) showed that orthotopic liver transplantation (OLT) was an effective treatment for patients with nonresectable, nonmetastatic HCC. There is growing evidence that expanding the MC does not adversely affect patient or allograft survival following OLT. The adult OLT programs in UNOS Region 4 reached an agreement allowing lesions outside MC (one lesion <6 cm, ,3 lesions, none >5 cm and total diameter <9 cm,[R4 T3]) to receive the same exception points as MC lesions. Kaplan,Meier curves and log-rank tests were used to compare survival data. Chi-squared and Mann,Whitney U tests were used to compare patient data. A p - value of <0.05 was considered significant. All statistical analyses were performed on SPSS 15 (SPSS, Chicago, IL). Four hundred and forty-five patients were transplanted for HCC (363-MC and 82-R4 T3). Patient demographics were found to be similar between the two groups. Three year patient, allograft and recurrence free survival between MC and R4 T3 were found to be 72.9% and 77.1%, 71% and 70.2% and 90.5% and 86.9%, respectively (all p > 0.05). We report the first regionalized multicenter, prospective study showing benefit of OLT in patients exceeding MC based on preoperative imaging. [source] Expression of X-linked inhibitor-of-apoptosis protein in hepatocellular carcinoma promotes metastasis and tumor recurrence,HEPATOLOGY, Issue 2 2008Ying-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] Benefit of downsizing hepatocellular carcinoma in a liver transplant populationALIMENTARY PHARMACOLOGY & THERAPEUTICS, Issue 3 2010J. 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] Meta-analysis: surveillance with ultrasound for early-stage hepatocellular carcinoma in patients with cirrhosisALIMENTARY PHARMACOLOGY & THERAPEUTICS, Issue 1 2009A. SINGAL Summary Background, A majority of studies investigating the accuracy of ultrasound for detecting hepatocellular carcinoma (HCC) do not reflect how this test is used for surveillance vs. diagnosis. Aim, To determine the performance characteristics of surveillance with ultrasound for the detection of HCC, particularly early HCC as defined by the Milan criteria. Methods, A systematic literature review using the MEDLINE and SCOPUS databases yielded six studies that evaluated the accuracy of ultrasound for HCC at any stage and 13 studies that were specific to early HCC. Results, Surveillance ultrasound detected the majority of tumours before they presented clinically, with a pooled sensitivity of 94%. However, ultrasound was less effective for detecting early HCC with a sensitivity of 63%. Alpha-fetoprotein provided no additional benefit to ultrasound. Meta-regression analysis demonstrated a significantly higher sensitivity for early HCC with ultrasound every 6 months than with annual surveillance. Current studies have limitations such as verification bias and are of suboptimal quality. Conclusions, Surveillance with ultrasound demonstrates limited sensitivity for early HCC, although this may be improved by testing at 6-month intervals. Currently available evidence evaluating surveillance ultrasound has significant limitations and future studies are necessary to determine optimal surveillance methods for early HCC. [source] Living donor liver transplantation in hepatocellular carcinoma beyond the Milan criteriaLIVER INTERNATIONAL, Issue 8 2008Hyun 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] Hepatocellular carcinoma: Ablate and wait versus rapid transplantationLIVER TRANSPLANTATION, Issue 8 2010John P. Roberts This opinion piece explores an "ablate and wait" strategy for improving the 5-year recurrence-free outcome of liver transplantation in patients with hepatocellular carcinoma. The Milan criteria delimit by tumor size and number a population of patients who have good survival after liver transplantation. The University of California San Francisco downstaging experience has shown that patients with a tumor burden outside the Milan criteria who undergo tumor ablation and a period of waiting have outcomes that rival those of patients who undergo transplantation within the Milan criteria because the tumor biology is allowed to become apparent by radiological studies during the waiting period. This experience has led to 2 conclusions: first, expansion beyond the Milan criteria should not occur without therapy directed to the tumor followed by a period of waiting to decrease the risk of recurrence, and second, for tumors within the Milan criteria, the same strategy should be considered. Liver Transpl, 2010. © 2010 AASLD. [source] Outcome of patients with hepatocellular carcinoma listed for liver transplantation within the Eurotransplant allocation system,LIVER TRANSPLANTATION, Issue 4 2008Michael Adler Although hepatocellular carcinoma (HCC) has become a recognized indication for liver transplantation, the rules governing priority and access to the waiting list are not well defined. Patient- and tumor-related variables were evaluated in 226 patients listed primarily for HCC in Belgium, a region where the allocation system is patient-driven, priority being given to sicker patients, based on the Child-Turcotte-Pugh (CTP) score. Intention-to-treat and posttransplantation survival rates at 4 years were 56.5 and 66%, respectively, and overall HCC recurrence rate was 10%. The most significant predictors of failure to receive a transplant in due time were baseline CTP score equal to or above 9 (relative risk [RR] 4.1; confidence interval [CI]: 1.7,9.9) and , fetoprotein above 100 ng/mL (RR 3.0; CI: 1.2,7.1). Independent predictors of posttransplantation mortality were age equal to or above 50 years (RR 2.5; CI: 1.0,3.7) and United Network for Organ Sharing pathological tumor nodule metastasis above the Milan criteria (RR 2.1; CI: 1.0,5.9). Predictors of recurrence (10%) were , fetoprotein above 100 ng/mL (RR 3.2; CI:1.1,10) and vascular involvement of the tumor on the explant (RR 3.6; CI: 1.1,11.3). Assessing the value of the pretransplantation staging by imaging compared to explant pathology revealed 34% accuracy, absence of carcinoma in 8.3%, overstaging in 36.2%, and understaging in 10.4%. Allocation rules for HCC should consider not only tumor characteristics but also the degree of liver impairment. Patients older than 50 years with a stage above the Milan criteria at transplantation have a poorer prognosis after transplantation. Liver Transpl 14:526,533, 2008. © 2008 AASLD. [source] Living donor liver transplantation for hepatocellular carcinoma: A single-center preliminary reportLIVER TRANSPLANTATION, Issue 6 2006Massimo Malagó 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. Liver Transpl 12:934,940, 2006. © 2006 AASLD. [source] Should the selection of children with hepatocellular carcinoma be based on Milan criteria?PEDIATRIC TRANSPLANTATION, Issue 1 2008Jean-Bernard Otte No abstract is available for this article. [source] Hepatocellular Carcinoma Patients Are Advantaged in the Current Liver Transplant Allocation SystemAMERICAN JOURNAL OF TRANSPLANTATION, Issue 7 2010K. Washburn Patients with hepatocellular carcinoma (HCC) within Milan criteria receive priority on the liver transplant waiting list (WL) and compete with non-HCC patients. Dropout from the WL is an indirect measure of transplant access. Competing risks (CR) evaluation of dropout for HCC and non-HCC patients has not previously been reported. Patients listed between 16 March 2005 and 30 June 2008 were included. Probability of dropout was estimated using a CR technique as well as a Cox model for time to dropout. Overall, non-HCC patients had a higher dropout rate from the WL than HCC patients (p < 0.0001). This was reproducible throughout all regions. In Cox regression, tumor size, model for end-stage liver disease (MELD) score and alpha fetoprotein (AFP) were associated with increased dropout risk. Multivariable analysis with CR showed that MELD score and AFP, were most influential in predicting dropout for HCC patients. The index of concordance for predicting dropout with the CR was 0.70. HCC patients appear to be advantaged in the current allocation scheme based on lower dropout rates without regard to geography. A continuous score incorporating MELD, AFP and tumor size may help to prioritize HCC patients to better equate dropout rates with non-HCC patients and equalize access. [source] The Diagnostic Conundrum and Liver Transplantation Outcome for Combined Hepatocellular-CholangiocarcinomaAMERICAN JOURNAL OF TRANSPLANTATION, Issue 5 2010C. Panjala Combined hepatocellular-cholangiocarcinoma (cHCC-CC) is a rare primary liver malignancy with mixed hepatocellular carcinoma (HCC) and cholangiocarcinoma (CC) histological features. It is almost impossible to obtain an accurate, preoperative noninvasive diagnosis of cHCC-CC with tumor markers or cross-sectional abdominal imaging due to the mixed histological features. Despite these difficulties, accurate cHCC-CC diagnosis remains an important goal with prognostic significance. In our study, we retrospectively reviewed the tumor markers: AFP and CA 19-9, and cross-sectional liver imaging, in light of liver explant findings, to identify and characterize cHCC-CC features followed by liver transplantation (LT) outcome analysis. The results from this 12 patient cohort failed to identify characteristic features for cHCC-CC. None of the imaging features helped to identify the cHCC-CC tumor and they mimicked either HCC or CC, depending on the degree of glandular differentiation expressed histologically. In our cHCC-CC LT recipients, the 1-, 3- and 5-year cumulative survival probabilities were 79%, 66% and 16%, respectively with a 5-year survival comparable to or better than LT for intrahepatic CC but poorer than LT for HCC following the Milan criteria. Conceivably explained by its cholangiocarcinoma component the LT outcome for this rare and hard to diagnose tumor appears poor. [source] Transarterial Chemoinfusion for Hepatocellular Carcinoma as Downstaging Therapy and a Bridge toward Liver TransplantationAMERICAN JOURNAL OF TRANSPLANTATION, Issue 5 2009W. De Luna Favorable outcomes after liver transplantation (LT) in patients with hepatocellular carcinoma (HCC) are well described for patients who fall within defined tumor criteria. The effectiveness of tumor therapies to maintain tumor characteristics within these criteria or to downstage more advanced tumors to fall within these criteria is not well understood. The aim of this study was to examine the response to transcatheter arterial chemoinfusion (TACI) in HCC patients awaiting LT and its efficacy for downstaging or bridging to transplantation. We performed a retrospective study of 248 consecutive TACI cases in 122 HCC patients at a single U.S. medical center. Patients were divided into two groups: those who met the Milan criteria on initial HCC diagnosis (n = 95) and those with more advanced disease (n = 27). With TACI treatment, 87% of the Milan criteria group remained within the Milan criteria and 63% of patients with more advanced disease were successfully downstaged to fall within the Milan criteria. In conclusion, TACI appears to be an effective treatment as a bridge to LT for nearly 90% patients presenting within the Milan criteria and an effective downstaging modality for over half of those whose tumor burden was initially beyond the Milan criteria. [source] 18F-FDG-Uptake of Hepatocellular Carcinoma on PET Predicts Microvascular Tumor Invasion in Liver Transplant PatientsAMERICAN JOURNAL OF TRANSPLANTATION, Issue 3 2009A. Kornberg Vascular invasion of hepatocellular carcinoma (HCC) is a major risk factor for poor outcome after liver transplantation (LT). The aim of this retrospective analysis was to assess the value of preoperative positron emission tomography (PET) using 18F-fluorodeoxyglucose (18F-FDG) in liver transplant candidates with HCC for predicting microvascular tumor invasion (MVI) and posttransplant tumor recurrence. Forty-two patients underwent LT for HCC after PET evaluation. Sixteen patients had an increased 18F-FDG tumor uptake on preoperative PET scans (PET +), while 26 recipients revealed negative PET findings (PET,) pre-LT. PET, recipients demonstrated a significantly better 3-year recurrence-free survival (93%) than PET + patients (35%, p < 0.001). HCC recurrence rate was 50% in the PET + group, and 3.8% in the PET,population (p < 0.001). PET + status was identified as independent predictor of MVI [hazard ratio: 13.4]. Patients with advanced PET negative tumors and patients with HCC meeting the Milan criteria had a comparable 3-year-recurrence-free survival (80% vs. 94%, p = 0.6). Increased 18F-FDG uptake on PET is predictive for MVI and tumor recurrence after LT for HCC. Its application may identify eligible liver transplant candidates with tumors beyond the Milan criteria. [source] Liver Transplantation for Recurrent Hepatocellular Carcinoma on Cirrhosis After Liver Resection: University of Bologna ExperienceAMERICAN JOURNAL OF TRANSPLANTATION, Issue 6 2008M. 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 TransplantationAMERICAN JOURNAL OF TRANSPLANTATION, Issue 8 2007M. 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] Risk of tumour progression in early-stage hepatocellular carcinoma after radiofrequency ablationBRITISH JOURNAL OF SURGERY (NOW INCLUDES EUROPEAN JOURNAL OF SURGERY), Issue 7 2009M. L. Fernandes Background: This study aimed objectively to quantify the risk of tumour progression beyond the Milan criteria following radiofrequency (RF) ablation for hepatocellular carcinoma (HCC) and to identify factors associated with tumour progression. Methods: Some 111 patients (136 tumours) with liver cirrhosis undergoing RF ablation for HCC within Milan criteria between February 2004 and June 2007 were enrolled in the study. Data were analysed retrospectively from a prospectively collected database. Results: The cumulative probability of tumour progression beyond the Milan criteria at 6, 12, 18, 24 and 36 months of RF ablation was 6·4, 11·0, 16·1, 21·2 and 44·8 per cent respectively. On multivariable analysis, factors independently associated with tumour progression were failure to achieve primary technique effectiveness (P = 0·005), ,-fetoprotein level above 200 ng/ml (P = 0·013) and Child,Pugh grade B cirrhosis (P = 0·034). Failure to achieve primary RF ablation technique effectiveness was associated with tumour location in segment VIII (P = 0·033), a cool-down temperature of 70 °C or less (P = 0·043) and multiple overlapping ablations (P = 0·029). Conclusion: This study provides clinicians with an objective risk of tumour progression beyond the Milan criteria after RF ablation at multiple time points. Primary technique failure is identified as a risk factor for tumour progression. Copyright © 2009 British Journal of Surgery Society Ltd. Published by John Wiley & Sons, Ltd. [source] | |||||||||||||||||||||||||