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A Vitale,
P Boccagni,
X Kertusha,
G Zanus,
F D'Amico,
E Lodo,
D Pastorelli,
R Ramirez Morales,
G Lombardi,
M Senzolo,
P Burra,
U Cillo
[show abstract]
[hide abstract]
ABSTRACT: There are scarce data on the use of sorafenib for the treatment of recurrent hepatocellular carcinoma (HCC) after orthotopic liver transplantation (OLT).
Ten patients were treated with sorafenib after OLT following the Italian Drug Agency guidelines: they had well-compensated liver function (Child-Pugh class A in the case of cirrhosis), intermediate-or advanced-stage HCC, good general condition (performance status 0), and not suitable for loco-regional therapies. Patients with HCC recurrence after OLT were treated with sorafenib (400 mg twice daily). Adverse events (AEs) were assessed using National Cancer Institute Common Toxicity Criteria of Adverse Events (NCI-CTCAE) v3.0 with tumor responses evaluated acording to modified Response Evaluation Criteria in Select Tumors) criteria.
Median duration of treatment was 10 months (range, 2-18). Seven patients (70%) received an additionally targeted therapy with mTOR inhibitors as part of their immunosuppressive regimen. Most common grade 3 AEs included diarrhea (50%), hand-foot skin reaction (30%), and fatigue (20%). Sorafenib had to be discontinued in 3 patients (30%) due to AEs and 4 additional patients (40%) required a dose adjustment. No deterioration of liver graft function occurred. Three patients (30%) stopped treatment due to radiological progression of HCC, whereas 3 are still using the drug. Median time to progression was 8 months (range, 2-16). Median survival from start of therapy was 18 months (range, 4- 36).
Our preliminary results suggest that sorafenib is a safe effective therapy for recurrent HCC after OLT.
Transplantation Proceedings 09/2012; 44(7):1989-91. · 1.00 Impact Factor
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E Gringeri,
M Polacco,
F E D'Amico,
D Bassi,
R Boetto,
F Tuci,
P Bonsignore,
G Noaro,
F D'Amico, A Vitale,
P Feltracco,
S Barbieri,
D Neri,
G Zanus,
U Cillo
[show abstract]
[hide abstract]
ABSTRACT: Ex situ ex vivo liver surgery represents a method to expand the surgical indications to treat otherwise unresectable liver tumors. We report the case of a 38-year old woman with hepatic metastasis from a pancreatoblastoma that was judged to be unresectable due to the involvement of the three hepatic veins. To treat the primary tumor, she underwent a pancreaticoduodenectomy, adjuvant chemotherapy, and thermal ablation of a liver metastasis. After appropriate preoperative study and with the permission of the ethics committee, she underwent ex situ ex vivo liver resection. The hepatectomy was performed by removing the whole liver en bloc with the retrohepatic vena cava. The inferior vena cava was reconstructed by interposition of a prosthetic graft. The ex situ ex vivo hepatic resection, a left hepatic lobectomy included the lesion in segments 1-5-7-8. The two hepatic veins were reconstructed using patches of saphenous vein. The organ was preserved continuously for 6 hours using hypothermic perfusion with 4°C Celsior solution. The liver was then reimplanted performing an anastomosis between the reconstructed hepatic veins and the caval prostheses. The patient was discharged at postoperative day 22 and is currently disease-free at 8 months after surgery and 44 months after the initial diagnosis. Ex situ, ex vivo liver surgery offers an additional option for patients with both primary and secondary liver tumors considered to be unresectable using traditional surgical approaches.
Transplantation Proceedings 09/2012; 44(7):1930-3. · 1.00 Impact Factor
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A W Avolio,
U Cillo,
M Salizzoni,
L De Carlis,
M Colledan,
G E Gerunda,
V Mazzaferro,
G Tisone,
R Romagnoli,
L Caccamo,
M Rossi, A Vitale,
A Cucchetti,
L Lupo,
S Gruttadauria,
N Nicolotti,
P Burra,
A Gasbarrini,
S Agnes
[show abstract]
[hide abstract]
ABSTRACT: Donor-recipient match is a matter of debate in liver transplantation. D-MELD (donor age × recipient biochemical model for end-stage liver disease [MELD]) and other factors were analyzed on a national Italian database recording 5946 liver transplants. Primary endpoint was to determine factors predictive of 3-year patient survival. D-MELD cutoff predictive of 5-year patient survival <50% (5yrsPS<50%) was investigated. A prognosis calculator was implemented (http://www.D-MELD.com). Differences among D-MELD deciles allowed their regrouping into three D-MELD classes (A < 338, B 338-1628, C >1628). At 3 years, the odds ratio (OR) for death was 2.03 (95% confidence interval [CI], 1.44-2.85) in D-MELD class C versus B. The OR was 0.40 (95% CI, 0.24-0.66) in class A versus class B. Other predictors were hepatitis C virus (HCV; OR = 1.42; 95% CI, 1.11-1.81), hepatitis B virus (HBV; OR = 0.69; 95% CI, 0.51-0.93), retransplant (OR = 1.82; 95% CI, 1.16-2.87) and low-volume center (OR = 1.48; 95% CI, 1.11-1.99). Cox regressions up to 90 months confirmed results. The hazard ratio was 1.97 (95% CI, 1.59-2.43) for D-MELD class C versus class B and 0.42 (95% CI, 0.29-0.60) for D-MELD class A versus class B. Recipient age, HCV, HBV and retransplant were also significant. The 5yrsPS<50% cutoff was identified only in HCV patients (D-MELD ≥ 1750). The innovative approach offered by D-MELD and covariates is helpful in predicting outcome after liver transplantation, especially in HCV recipients.
American Journal of Transplantation 09/2011; 11(12):2724-36. · 6.39 Impact Factor
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A Vitale,
R Ramirez Morales,
E dalla Bona,
M Scopelliti,
G Zanus,
D Neri,
F d'Amico,
E Gringeri,
F Russo,
P Burra,
P Angeli,
U Cillo
[show abstract]
[hide abstract]
ABSTRACT: The product between donor (D) age and recipient (R) Model for End-Stage Liver Disease (MELD) score at the moment of liver transplantation (LT) has been proposed as a potential D-R matching tool to reduce the risk of "futile" LT from using the MELD score as the main allocation tool. The aim of this study was to evaluate the prognostic ability of D-MELD among a cohort of Italian patients already selected for LT on the basis of a D-R matching philosophy.
We studied 303 consecutive adult patients undergoing first LT for chronic liver diseases with available D-MELD at the moment of LT from 2003 to 2009. Optimal donors were assigned to more severe cirrhotic patients (MELD ≥20); suboptimal organs were allocated to patients with hepatocellular carcinoma (HCC) not responsive to bridging therapies (specific priority score) or other exceptions with MELD <20. A suboptimal donor had age >70 years, severe steatosis by ultrasound, and/or body mass index >30 kg/m(2), partial liver, or hepatitis C (HCV) or B virus positivity.
Characteristics of the study group were a median age of 55 years (range, 27-68 years), HCV positivity in 164 patients (54%), HCC in 134 patients (44%), partial liver use in 25 (8%), MELD 15 (range, 6-40), D-age of 56 years (range, 18-87 years), and median D-MELD score 826 (range, 126-2,988). Overall graft survival was 84%, 79%, and 77% at 1, 3, and 5 years after LT, respectively. Logistic regression did not show a significant correlation between graft failure and D-MELD score in the absence of a significant D-MELD cutoff. Cox regression with D-MELD as the continuous variable showed a hazard ratio (HR) of 0.99 (95% confidence interval [CI], 0.99-1.00; P=NS); and with D-MELD as a dichotomic variable (≥0 to <1,600) an HR of 0.98 (95% CI, 0.63-1.77; P=NS).
The prognostic ability of D-MELD fails in OLT centers that use a more complex D-R matching policy.
Transplantation Proceedings 05/2011; 43(4):974-6. · 1.00 Impact Factor
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[show abstract]
[hide abstract]
ABSTRACT: Cirrhotic patients who need critical care support show high morbidity and mortality rates compared with other critically ill patients. Their prognosis is, in fact, influenced by both the severity of the underlying hepatic disease and the worsening of extrahepatic organ function. Clinicians and investigators have been persistently looking for objective scoring systems capable of providing accurate information on disease severity and short-term prognosis. Risk stratification helps differentiate patients who would not benefit from admission to the intensive care unit (ICU) from those who could achieve better outcomes once aggressively treated. The most common scores, ie, multiple organ dysfunction score, sequential organ failure assessment, and acute physiology and chronic health evaluation, developed in general ICUs to evaluate illness severity, have also been validated to predict the prognosis of cirrhotic patients admitted to the ICU. However, their absolute predictive value has been questioned. A weakness of common prediction models consists in not recognizing the continuum of physiological changes in critically ill decompensated cirrhotic patients. In addition, the predictive power to stratify individual risk is relatively low due to the great variability of liver dysfunction stages, the severity of related manifestations, and the number of nonfunctioning organs on admission. Probability models are not capable of predicting whether a patient will live or die with 100% accuracy, nor can they deny or confirm the indications for mechanical ventilation, vasopressor support or renal replacement therapy, or help to decide when to withhold or withdraw support. Because there are no absolute criteria to predict which cirrhotic decompensated patients will improve with normalization of organ function or deteriorate progressively, a scoring system should be regarded as an adjunct rather than a substitute for clinical judgment in the decision process concerning whether a patient should be admitted to the ICU.
Transplantation Proceedings 05/2011; 43(4):1079-84. · 1.00 Impact Factor
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G Zanus,
R Boetto,
E Gringeri, A Vitale,
F D'Amico,
A Carraro,
D Bassi,
P Bonsignore,
G Noaro,
C Mescoli,
M Rugge,
P Angeli,
M Senzolo,
P Burra,
P Feltracco,
U Cillo
[show abstract]
[hide abstract]
ABSTRACT: Surgical resection for malignant hepatic tumors, especially hepatocarcinoma (HCC), has been demonstrated to increase overall survival; however, the majority of patients are not suitable for resection. Radiofrequency ablation (RFA) is the most widely used modality for radical treatment of small HCC (<3 cm). It improves 5-year survival compared with standard chemotherapy and chemical ablation, allowing down-staging of unresectable hepatic masses. Microwave ablation (MWA) has been extensively applied in Asia and was recently introduced in the United States of America and Europe with excellent results, especially with regard to large unresectable HCC. Our single-center experience between May 2009 and October 2010 included application of MWA to 154 patients of median age ± standard deviation of 63.5 ± 8.5 years, 6 males, and 1 female, of mean Model for End-Stage Liver Disease (MELD) score (10.1 ± 3.8). The HCC included, hepatitis C virus (HCV)-related (n=70; 45.5%); alcool (ETOH)-related (n=42; 27%), hepatitis B virus (HBV)-related (n=16; 10.5%); and cryptogenic cases (n=26; 17%). The cases were performed for radical treatment down-staging for multifocal pathology or bridging liver transplantation to orthotopic (OLT) in selected patients with single nodules. A computed tomography (CT) scan was performed at 1 month after the surgical procedure to evalue responses to treatment. Among 6 selected patients who underwent OLT; 5 (83.3%) showed disease-free survival at one-year follow-up. The radical treatment achieved no intraoperative evidence of tumor spread or of pathological signs of active HCC among the explanted liver specimens. In conclusion, a MWA seemed to be a safe novel approach to treat HCC and could serve as a "bridge" to OLT and down-staging for patients with HCC.
Transplantation Proceedings 05/2011; 43(4):1091-4. · 1.00 Impact Factor
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E Gringeri,
D Bassi,
F E D'Amico,
R Boetto,
M Polacco,
E Lodo,
F D'Amico, A Vitale,
P Boccagni,
G Zanus,
U Cillo
[show abstract]
[hide abstract]
ABSTRACT: Cholangiocarcinoma has historically represented a major contraindication to liver transplantation at many centers because of its high recurrence rate and low disease-free survival rate, even after radical surgery. Novel neoadjuvant therapy protocols combined with demolitive surgery and liver transplantation seem to achieve successful results in terms of overall and disease-free survivals. Surgery frequently seems to be unsatisfactory only for patients also suffering from chronic cirrhosis or end-stage liver disease. We have reported a case of hilar cholangiocarcinoma occurring in a case of primary sclerosing cholangitis treated with neoadjuvant radiochemotherapy and endoscopic brachytherapy, followed by liver transplantation combined with pancreatoduodenectomy, who has survived free of disease for >8 years.
Transplantation Proceedings 05/2011; 43(4):1187-9. · 1.00 Impact Factor
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[show abstract]
[hide abstract]
ABSTRACT: Liver retransplantation (Re-OLT) is one of the most debated issues in medicine over the past decade. Re-OLT, currently is accepted for patients with irreversible failure of a hepatic graft caused by primary nonfunction (PNF), hyperacute/chronic rejection, or hepatic artery thrombosis (HAT); whereas it is still controversial for patients with recurrent viral disease, in particular hepatitis C virus (HCV) cirrhosis. Patient and graft survival rates are lower than those observed after primary liver transplantation (OLT). The aim of the present study was to analyze the risk factors that adversely affect survival after Re-OLT in a single center. Medical data were collected for 23 patients who underwent Re-OLT from November 2002 to December 2008 including six men and seven women of mean age of 51.3 years. The most frequent indications for Re-OLT were: PNF (69.5%; 16/23), HCV recurrence (8.6%; 2/23), or HAT (8.6%; 2/23). Mean Model for End-Stage Liver Disease (MELD) at Re-OLT was 27.7 (range = 9-40). After a mean follow-up of 37.4 ± 30 (standard deviation) months, 43% (10/23) of patients had died, including 70% within the first 2 months after Re-OLT. Sepsis represented the commonest cause of death (40%). Re-OLT was performed for PNF among 90% of succumbing patients. As regards dead patients, 4/10 were HCV(+) whose causes of death were sepsis (n=2), alcoholic cirrhosis (n=2), and undetermined (n=1). Comparing patients who died after liver Re-OLT versus alive patients, we did not find any significant difference in terms of mean MELD (28.6 vs 27; P=NS), MELD > 25 (60% vs 61.5%, P=NS), donor age > 60 years (30% vs 15.3%, P=NS), HCV(+) (40% vs 62%, P = NS), or time interval from OLT to Re-OLT (12.2 vs 777.7 days, P=NS). Patient survivals after Re-OLT were 67% at 3 years and 50% at 5 years, which were lower than those of first transplantations, as reported by other European and International Centers. Forty percent of deaths after Re-OLT occurred among HCV(+) recipients, but for reasons unrelated to HCV infection.
Transplantation Proceedings 05/2011; 43(4):1110-3. · 1.00 Impact Factor
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A.W. Avolio,
S. Agnes,
M.C. Lirosi,
M. Salizzoni,
A.D. Pinna,
B. Gridelli,
L. De Carlis,
M. Colledan,
G.E. Gerunda,
U. Valente, [......],
T.M. Manzia,
V. Tondolo,
M. Rendina,
V. Scuderi,
A. Perrella,
M. Angelico,
P. Burra,
S. Fagiuoli,
A. Gasbarrini,
U. Cillo
[show abstract]
[hide abstract]
ABSTRACT: A prognosis calculator was implemented (www.D-MELD.com) using determinants obtained on a national retrospective Italian Liver Transplant (LT) database (5946 LTs, 2002-2009). D-MELD (donor age x biochemical MELD) and other factors were evaluated. Differences among D-MELD deciles allowed their regrouping into 3 D-MELD classes (A <338, B 338-1628, C >1628). At 3 years, the odds ratio (OR) for death was 2.03 (95%CI, 1.44-2.85) in D-MELD class C versus B; the OR was 0.40 (95%CI 0.24-0.66) in class A versus B. Other predictors were HCV (OR=1.42; 95%CI 1.11-1.81), HBV (OR=0.69; 95%CI 0.51-0.93), re-transplant (OR=1.82; 95%CI 1.16-2.87) and low-volume Center (OR=1.48; 95%CI 1.11-1.99). The practical advantage of the D-MELD approach is that cases previously judged as risky, because of extreme-high MELD, can present a down-leveling of their risk when a young donor is matched (i.e., MELD=40, donor age=20 -> D-MELD=800); in the same way, when a extreme-high donor age is matched to a low- MELD candidate the risk wi
Hepatology. 01/2011; 54:670A.
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A.W. Avolio,
S. Agnes,
M.C. Lirosi,
M. Salizzoni,
A.D. Pinna,
B. Gridelli,
L. De Carlis,
M. Colledan,
G.E. Gerunda,
U. Valente, [......],
E. Tondolo,
M. Rendina,
A. Perrella,
E. Scuderi,
B. Antonelli,
C. De Waure,
T. De Feo,
P. Burra,
A. Gasbarrini,
U. Cillo
[show abstract]
[hide abstract]
ABSTRACT: Optimization of donor-recipient match represents one of the major challenges in liver transplantation. The variable donor organ quality and recipient liver disease severity explain the various types of match adopted. Sometimes the match or the mismatch is purely the results of chance. Nevertheless, in the majority of cases surgeons and hepatologists can take the opportunity to combine organ and recipient on the basis of specific risk assesment methods. In order to develop an algorithms able to guide organ allocation and avoid futile match (life-expectancy <50% at 5 years) a database was created and filled with data from 5946 liver transplants performed in 21 Italian Centers during the 2002-2009 period. A web-based prognostic calculator was developed using D-MELD (donor age x biochemical MELD) and other prognostic factors. The calculator is available online at the web address www.d-meld.com (ESOT password: D-MELD123). Using logistic regression at 3-years the following significant prognostic factors were
Transplant International. 01/2011; 24:33-34.
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A.W. Avolio,
S. Agnes,
M.C. Lirosi,
M. Salizzoni,
A.D. Pinna,
B. Gridelli,
L. De Carlis,
M. Colledan,
G.E. Gerunda,
U. Valente, [......],
T. Manzia,
E. Tondolo,
M. Rendina,
M. Barone,
A. Perrella,
M. Romano,
C. De Waure,
P. Burra,
A. Gasbarrini,
U. Cillo
[show abstract]
[hide abstract]
ABSTRACT: Intentional matching of liver transplant donor-recipient risk factors, supported by D-MELD (donor age null biochemical MELD), could offer a new therapeutic strategy with effects on survival. As yet, an extensive stratification of cases according to the futile transplant principle using a continous quantitative parameter has not been performed. To stratify the prognosis according to donor-recipient match and assess the predictive role of D-MELD together with covariates, a database detailing 5946 liver transplants performed in 21 Italian Centers (2002-2009) was analyzed. Primary endpoint was to evaluate the prognostic power of D-MELD and covariates in terms of 3-year patient survival. The futile-transplant cutoff (life-expectancy <50% at 5 years) was investigated. The database was divided into a training and a validation set. The adequacy of fit for both sets was tested using Hosmer-Lemeshow and C-statistics. Cases were stratified in ten D-MELD deciles. Significant differences among D-MELD deciles allowe
Journal of Hepatology. 01/2011; 54:S17.
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A Vitale,
M L Volk,
M Gambato,
G Zanus,
F D'Amico,
A Carraro,
A Pauletto,
P Bonsignore,
M Scopelliti,
M Polacco,
F Russo,
M Senzolo,
P Burra,
A Romano,
P Angeli,
U Cillo
[show abstract]
[hide abstract]
ABSTRACT: Long-term survival rates after orthotopic liver transplantation (OLT) for patients with hepatocellular carcinoma (HCC) of any size and number may now be predicted using the Metroticket calculator. The aim of this study was to evaluate the minimum post-OLT survival threshold that would justify the selection of a patient with HCC for OLT.
We used a Markov model, recently developed at the University of Michigan, which assumes that a patient with HCC should undergo OLT if his or her transplant benefit is greater than the cumulative harm to the rest of the waiting list (WL). In the base case, we considered a patient with a low survival perspective without OLT (5-year survival rate, 10%). The data sources to construct and validate the model were as follows: the Organ Procurement and Transplantation Network report, and our prospective database.
Our center was generally characterized by lower WL mortalities, although there were lower transplant probabilities for both HCC and non-HCC patients than the average US center. The proportion of HCC patients on the WL was higher in Padua (25%) than in the United States (10%). The calculated harm to the WL was 434 quality-adjusted days of life in Padua, and 957 in the United States (P < .01). The OLT benefit outweighed the harm to the WL when the 5-year post-OLT survival rate was higher than 30% in Padua, and 61% in the United States.
In a decision model including the concepts of transplantation benefit and harm to the WL, the minimum 5-year post-OLT survival threshold justifying the selection of a patient with HCC for OLT in Padua was 30%.
Transplantation Proceedings 05/2010; 42(4):1194-6. · 1.00 Impact Factor
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M Polacco, A Vitale,
M Valmasoni,
F D'Amico,
E Gringeri,
A Brolese,
G Zanus,
D Neri,
A Carraro,
A Pauletto,
E Romanelli,
S Lo Bello,
U Cillo
[show abstract]
[hide abstract]
ABSTRACT: Tumor progression before orthotopic liver transplantation (OLT) is the main cause of dropouts from waiting lists among patients with hepatocellular carcinoma (HCC). Performing a porto-caval shunt (PCS) before parenchymal liver transection has the potential to allow an extended hepatectomy in patients with decompensated liver cirrhosis, reducing portal hyperflow and therefore the sinusoidal shear-stress on the remnant liver. We report the case of a 59-year-old man affected by hepatitis C virus (HCV)-related decompensated liver cirrhosis (Child Pugh score presentation, C-10; Model for End Stage Liver Disease score, 18) and HCC (2 lesions of 2 and 2.8 cm). The patient began the evaluation to join the OLT waiting list, but, in the 3 months required to complete the evaluation, he developed tumor progression: 3 HCC lesions, the largest 1 with a diameter of about 4.4 cm. These findings excluded transplantation criteria and the patient was referred to our center. After appropriate preoperative studies, the patient underwent a major liver resection (trisegmentectomy) after side-to-side PCS by interposition of an iliac vein graft from a cadaveric donor. The patient overcame the worsened severity of cirrhosis. After 6 months of follow-up, he developed 2 other HCC nodules. He was then included on the waiting list at our center, undergoing OLT from a cadaveric donor at 8 months after salvage treatment. At 36 months after OLT, he is alive and free from HCC recurrence. Associating a partial side-to-side PCS with hepatic resection may represent a potential salvage therapy for patients with decompensated cirrhosis and HCC progression beyond listing criteria for OLT.
Transplantation Proceedings 05/2010; 42(4):1378-80. · 1.00 Impact Factor
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A Cucchetti, A Vitale,
M Del Gaudio,
M Ravaioli,
G Ercolani,
M Cescon,
M Zanello,
M C Morelli,
U Cillo,
G L Grazi,
A D Pinna
[show abstract]
[hide abstract]
ABSTRACT: Primary transplantation offers longer life-expectancy in comparison to hepatic resection (HR) for hepatocellular carcinoma (HCC) followed by salvage transplantation; however, livers not used for primary transplantation can be reallocated to the remaining waiting-list patients, thus, the harm caused to resected patients could be balanced, or outweighed, by the benefit obtained from reallocation of livers originating from HCC patients first being resected. A Markov model was developed to investigate this issue based on literature data or estimated from the United Network for Organ Sharing database. Markov model shows that primary transplantation offers longer life-expectancy in comparison to HR and salvage transplantation if 5-year posttransplant survival remains higher than 60%. The balance between the harm for resected patients and the benefit for the remaining waiting list depends on (a) the proportion of HCC candidates, (b) the percentage shifted to HR and (c) the median expected time-to-transplant. Faced with a low proportion of HCC candidates, the harm caused to resected patients was higher than the benefit that could be obtained for the waiting-list population from re-allocation of extra livers. An increased proportion of HCC candidates and/or an increased median time-to-transplant could lead to a benefit for waiting-list patients that outweighs this harm.
American Journal of Transplantation 03/2010; 10(3):619-27. · 6.39 Impact Factor
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[show abstract]
[hide abstract]
ABSTRACT: Background & aims: Recurrences of hepatocellular carcinoma (HCC) after hepatectomy in cirrhotic patients are either subclinical primary tumour metastases (early-recurrences) or denovo HCC arising from persistent fibrosis (late-recurrences). Interferon (INF) based therapy has the potential to reduce the occurrence of de-novo tumours but is expensive and its utility after hepatectomy has still to be established. Methods A Markov simulation model was built to analyze life-expectancy and cost-effectiveness (C/E) of INF-based treatment after hepatectomy. A hypothetical cohort of adult cirrhotic patients was followed over 10 years as they moved between different health states until death. Patients were divided into two groups: the nulltreatednull group started a weight-based peginterferon alpha-2b plus ribavirin therapy six weeks after hepatectomy, whereas the nullnon-treatednull group was followed with standard care. Results: Ten years after surgery, INF treatment increased lifeexpectancy by 11.1% with resp
Hepatology. 01/2010; 52:1196A-1197A.
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U Baccarani,
P Piselli,
D Serraino,
G L Adani,
D Lorenzin,
M Gambato,
A Buda,
G Zanus, A Vitale,
A De Paoli,
C Cimaglia,
V Bresadola,
P Toniutto,
A Risaliti,
U Cillo,
F Bresadola,
P Burra
[show abstract]
[hide abstract]
ABSTRACT: The purpose of this study is to describe de novo post-liver transplant malignancies and compare their frequency with incidence rates from Italian cancer registries.
Four hundred and seventeen patients subjected to liver transplantation, from 1991 to 2005, surviving for at least 30 days and without a previous diagnosis of cancer (including hepatocellular carcinoma), were evaluated for the development of de novo malignancies excluding non-melanoma skin cancers.
During a total follow-up time of 2856 person-years, 43 de novo malignancies were diagnosed in 43 liver transplantation recipients (10.3%). The most common cancers were non-Hodgkin lymphoma (9 cases), cancer of the head and neck (8 cases), Kaposi's sarcoma (6 cases) and esophageal carcinoma (5 cases). The 1, 3, 5 and 10 years estimated survival rates were 69%, 57%, 53% and 42%. Patients with de novo cancers had a lower 10-year survival rate than patients without cancers (58% versus 76%, p=0.005). The risk of cancer after liver transplantation was nearly 3-fold higher than that of the general population of the same age and sex (95% CI: 1.9-3.6). De novo tumour sites or types with significantly elevated SIR included Kaposi's sarcoma (SIR=144), non-Hodgkin lymphoma (SIR=13.8), esophagus (SIR=23.4), head and neck cancers (SIR=7) and cervix uteri (SIR=30.7).
Tumours after liver transplantation are associated with lower long-term survival, confirming that cancer is a major cause of late mortality in liver transplantation.
Digestive and Liver Disease 07/2009; 42(1):55-60. · 3.05 Impact Factor
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G Zanus,
A Carraro, A Vitale,
E Gringeri,
F D'Amico,
M Valmasoni,
F E D'Amico,
A Brolese,
P Boccagni,
D Neri,
N Srsen,
P Burra,
P Feltracco,
P Bonsignore,
M Scopelliti,
U Cillo
[show abstract]
[hide abstract]
ABSTRACT: Organ transplant recipients show an increased incidence of cancer ranging from 4% to 16% owing to several causes: immunosuppression, viral infection, individual predisposition, and so on.
We retrospectively reviewed the records of 43/683 (6.3%) recipients of 734 liver transplants performed from November 1991 to November 2008 who experienced a de novo neoplasm.
Alcohol abuse significantly increased the rate of all de novo neoplasms and particularly pharyngogastroesophageal cancers among population of liver transplant recipients. Minimization of immunosuppressive therapy is necessary to reduce the risk of a de novo neoplasm. Strict posttransplant follow-up is required to identify early gastroenteric tumors.
Transplantation Proceedings 06/2009; 41(4):1310-2. · 1.00 Impact Factor
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U Baccarani,
G L Adani,
D Serraino,
D Lorenzin,
M Gambato,
A Buda,
G Zanus, A Vitale,
P Piselli,
A De Paoli,
V Bresadola,
A Risaliti,
P Toniutto,
U Cillo,
F Bresadola,
P Burra
[show abstract]
[hide abstract]
ABSTRACT: The purpose of this study was to describe de novo post-orthotopic liver transplantation (OLT) malignancies for comparison with incidence rates in Italian cancer registries. Three hundred thirteen OLT patients engrafted from 1991 to 2006 and surviving 12 months without a previous diagnosis of cancer were evaluated for the development of de novo malignancies excluding nonmelanoma skin cancers. During a total follow-up time of 1753 PYs, 40 (12.8%) de novo malignancies were diagnosed in 40 recipients. The most common cancers were non-Hodgkin lymphoma (NHL; 20%), cancer of the head and neck (17%), Kaposi sarcoma (KS; 17%), and esophageal tumors (12%). The 1-, 3-, 5-, and 10-year estimated survival rates were 70%, 56%, 48%, and 39%. Patients with de novo cancers showed a lower 10-years survival rate (P = .0047) than patients without (39% vs 75%). The risk of cancer after OLT was 3-fold higher than that of the general population of the same age and gender (95% confidence interval [CI], 2.0-4.3). De novo tumor sites or types with significantly elevated standardized incidence ratios (SIRs) included KS (SIRs = 212), NHL (SIRs = 13.7), oesophagus (SIRs = 18.7), melanoma (SIRs = 10.1), and head and neck cancers (SIRs = 4.6). Tumors after OLT were associated with lower long-term survival, confirming that cancer is a major cause of late mortality.
Transplantation Proceedings 06/2009; 41(4):1303-5. · 1.00 Impact Factor
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A Vitale,
E Saracino,
F E D'Amico,
F Grigoletto,
P Burra,
P Angeli,
P Boccagni,
A Brolese,
G Zanus,
D Neri,
E Gringeri,
F D'Amico,
M Valmasoni,
A Carraro,
M Gambato,
P Feltracco,
A Romano,
M Buggio,
D F D'Amico,
U Cillo
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ABSTRACT: The system that controls the waiting list (WL) and organ allocation for liver transplantation (OLT) seeks to achieve 3 main goals: objectivity, low dropout risks and good post-OLT results. We sought to prospectively validate a priority allocation model that is believed to achieve objectivity without penalizing dropout risk and post-OLT results.
We evaluated a study group of 272 patients enrolled in 2006-2007. WL candidates were divided into 2 categories: cirrhotic patients classified according to Model for End-Stage Liver Disease (MELD) score (MELD list and patients with hepatocellular carcinoma (HCC) organized according to a specific score (non-MELD list). The allocation algorithm for donor-recipient match assigned an optimal graft to the first MELD candidate with a MELD score of >or=20; a suboptimal graft, to the first non-MELD patient. A respective control group of 327 patients transplanted from 2003-2006 was characterized by a unique WL with a free allocation policy. We performed an interim analysis of this prospectively controlled study.
Although the study group showed a lower percentage of OLT (P < .05) than the control group (37% vs 45%), it selected patients for OLT based on a higher MELD score (P < .05), thus obtaining similar dropout, post-OLT survivals, and intention-to-treat (ITT) survival probabilities as the controls. Among MELD patients, we observed a significantly reduced dropout and better ITT survival profiles than those of the control group (P = .02), whereas the similar results were delivered among non-MELD patients (P > .05). Among patients with a MELD score of >or=20, the prevalences of suboptimal grafts (0% vs 48%) and of early graft losses (0% vs 21%) were lower in the study than in the control group (P < .05).
We prospectively validated a priority allocation model based on objective criteria that achieved high ITT survival rates.
Transplantation Proceedings 05/2009; 41(4):1092-5. · 1.00 Impact Factor
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A Vitale,
P Boccagni,
A Brolese,
D Neri,
N Srsen,
G Zanus,
D Pagano,
A Pauletto,
P Bonsignore,
M Scopelliti,
F E D'Amico,
G Ometto,
M Polacco,
P Burra,
M Gambato,
P Feltracco,
A Romano,
U Cillo
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ABSTRACT: Tumor progression before liver transplantation (OLT) is the main cause of dropout from the waiting list (WL) of patients with hepatocellular carcinoma (HCC). The aim of this study was to show a correlation between adopted dropout criteria and dropout/intention-to-treat survival rates of WL HCC patients.
The study period was 2000 to 2007. The dropout criteria were macroscopic vascular invasion, metastases, or a poorly differentiated tumor. Adult patients with benign chronic liver disease enlisted for primary OLT in the same period represented the control group.
Dropout probability of study (n = 128) versus control group (n = 377) subjects was similar: namely, 12% at 1 year in both groups (P = NS). Intention-to-treat survival curve of the HCC group overlapped that of the benign group (5-year survival rates were 73% and 71%, respectively; P = NS). At the time of listing, 103 study group patients were within the Milan criteria (MC): among these patients, 29 (28%) showed tumor progression beyond MC before OLT. Simulating the dropout of these 29 patients at the time of diagnosis of tumor progression, we compared the dropout probability of the 103 patients within MC with that of the control group. As a result, the 1- and 2-year dropout rates became 37% and 53%, respectively, in the study group, which were significantly higher than those in the controls (P < .01).
HCC patients on the WL showed a significantly greater dropout rate than subjects with benign cirrhosis when too restrictive radiologic dropout criteria were used. The adoption of criteria more related to biological aggressiveness of a tumor decreased the dropout risk for HCC patients without impairing their intention-to-treat survival rates.
Transplantation Proceedings 05/2009; 41(4):1264-7. · 1.00 Impact Factor
