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Liver transplant could be considered for certain tumors even if there is still dubious indication, as in the case of hepatic small vessels neoplasms that pose a difficult differential diagnosis with liver angiosarcoma. Liver transplant could be the best choice for patients with stable or slow-progressing tumors, for young patients with impaired quality of life, and when it would use organs that would be otherwise discarded but are capable of affording a good function. Vascular tumors are very heterogeneous cancers and our case represents the first description of a new histologic lesion that cannot be included in any of the pre-existing diagnostic categories. In our paper we want to present our decision to transplant a patient in whom the diagnosis was hepatic small vessels neoplasms (but was still in doubt for angiosarcoma as suggested by pathologists form other institutions). Furthermore, we want to highlight that after liver transplant, a new lesion never described before resulted from the specimen analysis that does not fit any of the pathologic diagnostic categories. This finding could open a scenario for additional improvement in molecular analysis in order to differentiate liver vascular tumors or even single lesion histotypes. This article emphasizes how little we know about the real behavior of liver vascular tumors and their clinical and therapeutic outcomes; we want to raise a question about the possibility for liver transplant in the setting of tumors not yet fully known and in which, in cases of diagnostic doubts, this option has been traditionally excluded, possibly bypassing ethical implications by using marginal donors., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Background: Liver transplantation (LT) is an established treatment for patients with end-stage liver disease. The significant advances in surgical technique, immunosuppression therapy, and anesthesiological management have dramatically improved short- and long-term outcomes. The aim of this study is to correlate specific surgical and anesthesiological variables with causes of early death in LT recipients., Methods: A retrospective observational analysis of adult patients who underwent LT in the period 2012 to 2016 and died within 90 days following LT was conducted. Exclusion criteria were intraoperative death, split liver, and domino transplant. Death was considered a dependent variable and classified into 3 different groups: death by sepsis, vascular events not related to the graft, and primary non-function. Donor and recipient variables were considered and analyzed using Fisher's exact test., Results: Statistically significative associations (P value < .05) were found between renal function support, retransplantation, and the number of fresh frozen plasma units transfused in one group and early death due to sepsis in the other., Conclusions: This study identified some risk factors associated with the specific cause of early death in liver transplantation. The clinical implications of these findings are the ability to stratify patients at high risk of early death by planning more intensive and accurate management for them., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Introduction: Hepatic artery thrombosis (HAT) is a well-recognized complication of liver transplantation (LT). HAT is an important risk factor for infectious, in particular hepatic abscess, which can cause graft loss and increasing morbidity and mortality., Case Report: We present a case report of complicated LT in a 52-year-old Caucasian man with primary sclerosing cholangitis. In 2007 the patient was included on the waiting list in Padua for LT. In 2012 the patient underwent percutaneous transhepatic biliary drainage for bile duct stricture, complicated with acute pancreatitis. A diagnostic laparoscopy was performed with choledochotomy and Kehr's T tube drainage. On February 14, 2012, the patient underwent LT with arterial reconstruction and choledochojejunostomy. The postoperative course was complicated with HAT, multiple liver abscesses, and sepsis associated with bacteremia due to Enterococcus faecium despite massive intravenous antibiotic therapy and percutaneous drainages. On November 28, 2012, the patient underwent retransplantation. Four years after transplantation the patient is still in good general condition., Conclusion: Hepatic abscess formation secondary to HAT following LT is a major complication associated with important morbidity and mortality. In selected cases retransplantation should be considered as our case demonstrates., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Background: Liver transplantation (LT) for hepatocellular carcinoma (HCC) can be used for tumor recurrence after liver resection (LR) both for initially transplant-eligible patients as conventional salvage therapy (ST) and for non-transplant-eligible patients (beyond Milan criteria) with a goal of downstaging (DW). The aim of this study was to compare the intention-to-treat (ITT) survival rates of patients who are listed for LT, according to these two strategies., Methods: We analyzed a prospective database of 399 consecutive patients who underwent hepatic resection for HCC from 2002 to 2011 to identify patients included in the waiting list for tumor recurrence. Intention-to-treat (ITT) survivals were compared with those of patients resected for HCC within and beyond Milan criteria in the same period and not included in the LT waiting list., Results: The study group consisted of 42 patients, 28 in the ST group (within Milan) and 14 in the DW group (beyond Milan). The 5-year ITT survival rate was similar between the 2 groups, being 64% for ST and 60% for DW (P=.84). Twenty-five patients (15 ST and 10 DW) underwent LT, 13 (10 ST and 3 DW) were still awaiting LT, 4 (3 ST and 1 DW) dropped out of the waiting list because of tumor progression, and 7 (5 ST [33%] and 2 DW [20%]) had tumor recurrence. The 5-year ITT survival of ST patients was similar to that of 252 in-Milan HCC patients resected only (P=.3), whereas 5-year ITT survival of DW patients was significantly higher (P<.01) than that of 105 beyond-Milan HCC patients resected only., Conclusions: LR seems to be a safe and effective therapy both as alternative to transplantation and as downstaging strategy for intermediate-advanced HCC. The survival benefit of salvage LT, however, seems to be higher in the 2nd than in the 1st group., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Introduction: Liver transplantation (OLT) is the treatment of choice for advanced hepatic disease. The growing gap between waiting list patients and the number of donations has led to acceptance of less than optimal donors. The aim of this study was to evaluate the 5-year experience with anti hepatitis B core antigen (HBc)-positive liver donors., Patients and Methods: All recipients of anti-HBc-positive grafts from January 2005 to December 2010 were evaluated annually after OLT for liver disease etiology, Model for End-Stage Liver Disease (MELD) score, and the presence of hepatocellular carcinoma (HCC) liver biopsy histology and serology for hepatitis B virus (HBsAg, anti-HBs, HBV-DNA), hepatitis C virus, and hepatitis D virus as well as antiviral prophylaxis to prevent de novo HBV., Results: Among the 249 OLT performed from January 2005 to December 2010, (9.3%) cases used grafts from anti-HBc-positive donors. Etiologics of liver disease among the recipients were HBV (n = 13; 32.5%), HCV (n = 13; 32.5%) or other causes (n = 14; 35%). In 20 of the 40 patients (50%), HCC was found in the explanted organ. Of 40 recipients of anti-HBc-positive grafts 11 died, and 7 (17.5%) required retransplantation. Various regimens were employed as post-transplantation antiviral prophylaxis: (l) Immune globulin (25.8%); (2) Oral antiviral drugs (9.7%); and (3) combined prophylaxis (51.6%) or no treatment (12.9%). No difference was observed in patient or graft survival in relation to the etiology of liver disease, the MELD score, or the presence of HCC at the time of OLT, except graft survival was significantly reduced among recipient who underwent transplantation for non-HBV or non-HCV liver diseases compared with those engrafted due to viral hepatitis (P = .0062). No difference was observed in histologic features (grading and staging) compared with the antiviral prophylactic therapy; the 2 patients (5%) who developed de novo HBV had not received prophylaxis after OLT., Conclusions: Matching anti-HBc-positive grafts to recipients without HBV infection before OLT, may be especially safe., (Copyright © 2013. Published by Elsevier Inc.)

Advances in surgical techniques and follow-up of patients with complex congenital heart disease who were corrected in childhood increasingly survive to adolescence or adulthood. Increasingly anesthesiologists encounter these cases for major noncardiac surgery, including orthotopic liver transplantation (OLT) wherein there is an augmented risk of significant perioperative hemodynamic instability. We performed a successful OLT in a 12-year-old boy with end-stage cryptogenetic liver fibrosis and hepatopulmonary syndrome who was born with a double outflow right ventricle, pulmonary atresia, and pulmonary artery hypoplasia corrected at the age of 1 month. By the time he was considered for OLT his altered pulmonary valve apparatus resulted in severe pulmonary regurgitation, dilated right atrium and ventricle, and elevated right heart pressures. After a temporarily successful angioplasty he was at first placed on the waiting list, then removed, and finally relisted following implantation of a prosthetic pulmonary valve that resulted in significant reduction of right heart pressures., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Background: Polycystic liver disease (PLD) is due to a genetic disorder and frequently coexists with polycystic kidney disease (PKD). If the cysts produce symptomatology owing to their number and size, many palliative treatments are available. When none of the liver parenchyma is spared, or kidney insufficiency is marked, the only potentially curable treatment is liver transplantation (LT)., Case Report: A 49-year old woman, diagnosed with PLD and PKD, was listed in January 2008 for combined LT and kidney transplantation (KT). A compatible organ became available 8 months later. Despite preserved liver function, the patient's clinical condition was poor; she experienced dyspnea, advanced anorexia, abdominal pain, and severe ascites. At LT, which took 9 hours and was performed using the classic technique, the liver was hard, massive in size (15.5 kg), and not dissociable from the vena cava. The postoperative course was complicated by many septic episodes, the last one being fatal for the patient at 4 months after transplantation., Discussion: LT for PLD in many series shows a high mortality rate. The Model for End-Stage Liver Disease (MELD) score does not stage patients properly, because liver function is usually preserved. The liver can achieve a massive size causing many symptoms, especially malnutrition and ascites; in this setting LT is the only possible treatment. Patients with a low MELD score undergo LT with severe malnutrition that predisposes them to greater susceptibility to sepsis. To identify predictor factors, beyond MELD criteria that relate to the increased liver volume before development of late symptoms is essential to expeditiously treat patients with the poorest prognosis to improve their outcomes., (Copyright © 2012 Elsevier Inc. All rights reserved.)

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., (Copyright © 2012 Elsevier Inc. All rights reserved.)

We previously reported that subnormothermic machine perfusion (sMP; 20°C) is able to improve the preservation of livers obtained from non-heart-beating donors (NHBDs) in rats. We have compared sMP and standard cold storage (CS) to preserve pig livers after 60 minutes of cardiac arrest. In the sMP group livers were perfused for 6 hours with Celsior at 20°C. In the CS group they were stored in Celsior at 4°C for 6 hours as usual. To simulate liver transplantation, both sMP- and CS-preserved livers were reperfused using a mechanical continuous perfusion system with autologus blood for 2 hours at 37°C. At 120 min after reperfusion aspartate aminotransferase levels in sMP versus CS were 499 ± 198 versus 7648 ± 2806 U/L (P < .01); lactate dehydrogenase 1685 ± 418 versus 12998 ± 3039 U/L (P < .01); and lactic acid 4.78 ± 3.02 versus 10.46 ± 1.79 mmol/L (P < .01) respectively. The sMP group showed better histopathologic results with significantly less hepatic damage. This study confirmed that sMP was able to resuscitate liver grafts from large NHBD animals., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Background: There are scarce data on the use of sorafenib for the treatment of recurrent hepatocellular carcinoma (HCC) after orthotopic liver transplantation (OLT)., Patients and Methods: 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., Results: 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)., Conclusion: Our preliminary results suggest that sorafenib is a safe effective therapy for recurrent HCC after OLT., (Copyright © 2012 Elsevier Inc. All rights reserved.)

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., (Copyright © 2011 Elsevier Inc. All rights reserved.)

Background: Hepatic resection is the gold standard of therapy for primary and secondary liver tumors, but few patients are eligible for this procedure because of the extent of their neoplasms. Improvements in surgical experience of liver transplantation (OLT), hepatic resection and preservation with sub-normothermic machine perfusion (MP) have prompted the development of a new model of large animal autotransplantation., Methods: Landrace pigs were used in this experiment. After intubation, hepatectomy was performed according to the classic technique. The intrahepatic caval vein was replaced with a homologous tract of porcine thoracic aorta. The liver was perfused with hypothermic Celsior solution followed by MP at 20 °C with oxygenated Krebs solution. An hepatectomy was performed during the period of preservation, which lasted 120 minutes, then the liver was reimplanted into the same animal in a 90° counterclockwise rotated position. The anastomoses were performed in the classic sequence. Samples of intravascular fluid, blood and liver biopsies were obtained at the end of the period of preservation in MP and again at 1 and 3 hours after liver reperfusion to evaluate graft function and microscopic damage., Results: All animals survived the procedure. The peak of aspartate aminotransferase was recorded 60 minutes after reperfusion and the peak of alanine aminotransferase and lactate dehydrogenase after 180 minutes. Histopathologic examination under the light microscope identified no necrosis or congestion. Intraoperative echo-color Doppler documented good patency of the anastomosis and normal venous drainage., Conclusion: This system made it possible to perform hepatic resections and vascular reconstructions ex situ while preserving the organ with mechanical perfusion (ex vivo, ex situ surgery). Improving surgical techniques regarding autotransplantation and our understanding of ischemia-reperfusion damage may enable the development of interesting scenarios for aggressive surgical treatment or radiochemotherapy options to treat primary and secondary liver tumors unsuitable for conventional in situ surgery., (Copyright © 2011 Elsevier Inc. All rights reserved.)

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., (Copyright © 2011 Elsevier Inc. All rights reserved.)

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., (Copyright © 2011 Elsevier Inc. All rights reserved.)

Background: 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., Methods: 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., Results: 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)., Conclusion: The prognostic ability of D-MELD fails in OLT centers that use a more complex D-R matching policy., (Copyright © 2011 Elsevier Inc. All rights reserved.)

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., (Copyright © 2011 Elsevier Inc. All rights reserved.)

Background and Aim: The effectiveness of any treatment depends not only on the choice of therapy, but also, to a large extent, on the patient's active cooperation. Adherence to medical prescriptions and particularly to immunosuppressive therapy is crucial to prevent medical complications that negatively influence graft function and patient survival after organ transplantation. The aim of this study was to assess, among patients who underwent solid organ transplantation, nonadherent behaviors (NAB) to immunosuppressive therapy, to correct lifestyle, and to general medical prescriptions., Materials and Methods: We evaluated patients who underwent solid organ transplantation from March 2008 to June 2009. All participants completed an anonymous 15-item questionnaire to assess NAB., Results: We enrolled 218 organ transplant patients: 103 liver, 50 kidney, 52 heart, and 13 lung. There were 152 men and the overall age was 52.2 ± 0.8 years (mean ± standard deviation [SD]) time from transplantation, 83.6 ± 4.5 months (mean ± SD). Overall 37.9%, 38.8%, and 12.8% of patients reported nonadherence to immunosuppressive therapy, to correct lifestyle, and to general medical prescriptions, respectively. Considering nonadherence to immunosuppressive therapy and to general prescriptions, the percentage of kidney transplant patients who referred NAB was significantly lower compared with other organ transplant patients (P = .008 and P = .04, respectively). Nonadherent patients to immunosuppressive therapy and to general medical prescriptions displayed a longer interval from transplantation compared with adherent patients (P = .02 and P = .03, respectively). Among patients nonadherent to the correct lifestyle, the rates of men and of patients with disability pension were significantly higher compared to adherent patients (P = .001 and P = .002, respectively)., Conclusions: Poor adherence to medical prescriptions and to adequate lifestyle is common among organ transplant patients, especially those who have undergone liver transplantation. Psychoeducational interventions for transplanted patients and their families are needed to improve adherence., (Copyright © 2011 Elsevier Inc. All rights reserved.)

Background: 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., Methods: 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., Results: 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., Conclusions: 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%., (Copyright (c) 2010 Elsevier Inc. All rights reserved.)

Infectious complications contribute to significant patient morbidity and mortality in orthotopic liver transplant (OLT) recipients. Early central nervous system (CNS) involvement (within the first month after OLT) by infectious disease is essentially set off by aggressive surgical procedures, severe morbid conditions of the pretransplant period, initial graft dysfunction, permanence of intravascular catheters, and prolonged mechanical ventilation. The type and severity of CNS infection may be determined by many factors, such as posttransplant adverse events; prolonged or repeated surgery with massive intraoperative transfusions, net state of immunosuppression, recurrence of infections by immunomodulating viruses, and retransplantation. Bacteria, viruses, and fungi can spread to the CNS just as they affect the abdomen, blood stream, respiratory tract, urine, drainages, etc. Because immunosuppressive drugs may modify the clinical presentation of CNS infections, it is very important to maintain vigilance and attend to minor neurologic symptoms. Special attention should therefore be given to cerebral investigation in patients with prolonged pulmonary contamination, unresponsive fever, and heavy corticosteroid therapy, primarily when they became disoriented, develop seizures, or exhibit focal neurologic signs. Clinical response to medical therapy may sometimes be poor because of chronic encapsulation of the pathogen, development of resistance, and/or catastrophic hemorrhagic complications., (Copyright (c) 2010. Published by Elsevier Inc.)

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., (Copyright (c) 2010 Elsevier Inc. All rights reserved.)

Background: 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., Methods: 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., Results: 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)., Conclusion: 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.

Background/aim: The definition of an extended criteria donor for orthotopic liver transplantation (OLT) remains controversial. The donor risk index (DRI) has become the main tool to define the marginality of hepatic grafts in the United States. The aim of this study was to prospectively evaluate the prognostic ability of DRI among a cohort of Italian patients undergoing OLT., Methods: From December 2006 to March 2008, we prospectively calculated DRI in all consecutive cadaveric grafts. Recipient inclusion criteria were: adult patients with chronic liver disease enlisted for primary OLT. The primary end point was the incidence of primary graft dysfunction (PDF), namely, aspartate aminotransferase (AST) >2000 U/mL and prothrombin time <40% on postoperative days 2-7., Results: We enrolled 74 donor-recipient pairs fulfilling the inclusion criteria. Donor characteristics included DRI 1.7 (range, 0.9-3.0); age 57 years (range, 18-81); ultrasound signs of steatosis in 22 donors (30%); and ischemia time was 536 minutes (range, 290-690). Recipient characteristics are: age 55 years (range, 27-68); hepatocellular carcinoma in 36 subjects (49%); MELD was 16 (range, 7-39); and Child-Pugh score was 8 (range, 6-14). In terms of the primary end points, the DRI did not provide a significant PDF predictor (P = .84). Among all evaluated donor and recipient variables, the following were related to the incidence of graft PDF: donor age (P = .07), ultrasound signs of steatosis (P = .02), donor AST (P = .05), cell saver infusion (P = .07), and warm (P = .04) and cold ischemia (P = .07) times., Conclusion: The preliminary data of this study showed a poor correlation between DRI and PDF incidence after OLT.

Introduction: 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., Materials and Methods: 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., Conclusion: 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.

Background: 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., Methods: 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., Results: 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)., Conclusions: We prospectively validated a priority allocation model based on objective criteria that achieved high ITT survival rates.

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.

Background/aim: Prognosis assessment in surgical patients with hepatocellular carcinoma (HCC) remains controversial. The most widely used HCC prognostic tool is the Barcelona Clinic Liver Cancer (BCLC) classification, but its prognostic ability in surgical patients has not been yet validated. The aim of this study was to investigate the value of known prognostic systems in 400 Italian HCC patients treated with radical surgical therapies., Methods: We analyzed a prospective database collection (400 surgical, 315 nonsurgical patients) observed at a single institution from 2000 and 2007. By using survival times as the only outcome measure (Kaplan-Meier method and Cox regression), the performance of the BCLC classification was compared with that of Okuda, Cancer of the Liver Italian Program, United Network for Organ sharing TNM, and Japan Integrated Staging Score staging systems., Results: Two hundred twenty-five patients underwent laparotomy resection; 55, laparoscopic procedures (ablation and/or resection); and 120, liver transplantations. In the surgical group, BCLC proved the best HCC prognostic system. Three-year survival rates of patients in BCLC Stages A, B, and C were 81%, 56%, and 44% respectively, (P < .01); whereas all other tested staging systems did not show significant stratification ability. When all 715 HCC patients were considered, surgery proved to be a significant survival predictor in each BCLC stage (A, B, and C)., Conclusions: BCLC staging showed the best interpretation of the survival distribution in a surgical HCC population. The BCLC treatment algorithm should consider the role of surgery also for intermediate-advanced stages of liver disease.

Background and Aim: Hepatitis C virus (HCV)-related cirrhosis is one of the leading indication for liver transplantation (LT) and a major risk factor for the development of hepatocellular carcinoma (HCC). HCV recurrence after LT is universal. This study evaluated HCV recurrence and survival in patients transplanted for HCV and HCC., Methods: We evaluated all adults transplanted for HCV cirrhosis between January 1999 and December 2006, HCC was diagnosed on the explant and HCV recurrence confirmed on protocol liver biopsies performed at 6 months and yearly after LT. The sustained viral response (SVR) was defined as HCV-RNA undetectable at 6 months after therapy discontinuation. The patient survival rates were assessed with Kaplan-Meier curves and the chi-square test was used when appropriate., Results: Two hundred sixteen patients underwent LT for HCV including 153 men and 63 women of mean age 54 years with a mean follow-up of 35 months. There were 71 (33%) HCC(+) patients. At 1, 3, and 5 years from LT severe fibrosis (Scheuer 3-4) due to the HCV recurrence was reported in 18%, 14%, and 11% for HCC(+) and 14%, 16%, and 28% for HCC(-) patients respectively (P=NS). HCC recurred only in 3 (4%) patients at a mean follow-up of 3 years. Patients who received antiviral treatment after LT were 10% HCC(+) and 12% HCC(-) patients (P=NS). SVR was seen in 3/7 (43%) of HCC(+) and in 10/18 (55%) of HCC(-) patients (P=NS). At 1, 3, and 5 years the patient survivals was 91%, 86%, and 86% for HCC(+) and 94%, 86%, and 83% for HCC(-) patients, respectively (P=NS)., Conclusions: Severe fibrosis due to HCV recurrence, which increases over time, involves one third of transplanted patients at 5 years after LT. The long-term survival was identical among HCC(+) compared to HCC(-) recipients. The recurrence of HCC was negligible and did not affect patient survival.

Progress in diagnosis and treatment has led to an increased number of transplantation patients who consequently have immunological depression and emergence of tumors. The incidence of cervical neoplasia, according to previous studies, is 11%; this tumor is the only one that can be investigated by screening before and after a graft. Our purpose was to evaluate whether transplanted patients showed an increased incidence of genital human papilloma virus (HPV) infection and whether this infection produced greater progression of disease in cases of low-risk HPV infections. Our study involved 151 transplant patients who underwent Papanicolaou (Pap) and HPV tests. Patients listed for grafts underwent Pap and HPV tests 6 months before and 6 months after transplantation. All patients had negative Pap tests before their grafts. After their grafts 16 patients (10.59%) had negative Pap tests, but positive viral typing. Eleven patients (7.28%) showed positive Pap tests, 6 of whom had low-grade squamous intraepithelial lesion (SIL) and 5 patients high-grade SIL. The final HPV infection incidence (15.23%) was consistent with the literature. The incidence of lower female genital tract intraepithelial lesions (7.28%) was higher than the healthy population or analogous studies (4.5%-8.5%). We showed a constant association between high-risk HPV infection and gynecologic intraepithelial neoplasia, whereas there was no association between low-risk broods HPV infection and neoplasia. In conclusion, screening should start at almost 6 months before grafting to avoid an irreversible situation that is difficult to treat.

Background: Up to 15% of liver transplant candidates have asymptomatic coronary artery diseases, which increase the risk of cardiac complications during and after transplantation. The aim of this study was to prospectively investigate the usefulness of an integrated cardiological approach in cirrhotic patients undergoing liver transplantation., Methods: Twenty-four consecutive patients undergoing evaluation for liver transplantation were studied by assessing risk factors for coronary artery diseases, electrocardiogram with QTc interval determination, chest X-ray, echocardiography, 24-hour Holter monitor, myocardial perfusion scintigraphy (99mTc)MIBI-GSPECT at rest and after dipyridamole infusion. Cardiac (123)I-metaiodobenzylguanidine (MIBG) scan and coronarography were performed in patients with myocardial perfusion defects. Twenty three of 24 patients underwent successful liver transplantation; one patient died on the waiting list., Results: Before liver transplantation, 29% of patients were diabetic and 41% were smokers. Eleven of 24 patients had a prolonged QTc interval, and 3/24 had positive myocardioscintigraphy after dipyridamole infusion: in two coronarography was negative, while the (123)I-MIBG washout was altered. No cardiac events were recorded during the short-and long-term follow-up after surgery., Conclusions: Predictive value of positive cardiac (99mTc)MIBI-GSPECT in patients with liver cirrhosis is low, and this may be due to alterations of cardiac microvascular tone as showed by cardiac (123)I-MIBG scan.

Objectives: To identify the most significant variables in determining if candidates with past or current addictions can be considered for liver transplantation., Methods: Data relating to 58 cases from January 2001 to December 2003 were collected and analyzed., Results: The decisional algorithm identified by discriminant analysis is based on the following variables: the duration of remission, treatment adherence, and the presence of a valid help relationship. Candidates undergoing initial remission (up to 12 months) must demonstrate both adherence and affective support; those with over 5 years of remission, however, are considered sufficiently reliable. A positive judgment is significantly correlated to overall survival and clinical improvement even without transplantation., Conclusions: In toxicological evaluation, treatment adherence and the presence of a valid help relationship for patients in remission from addictions can improve the selection criteria for liver transplantation, making it more dependable.

Aim: To assess the indications and results of endoscopic retrograde cholangio-pancreatography (ERCP) in patients who have undergone ortotopic liver transplantation (OLT)., Methods: We reviewed data from 42 consecutive patients who underwent ERCP for biliary complications after OLT over an 8-year period, in particular recording indications and success of the treatment after a mean of 17 months follow-up., Results: Cholangiograms performed in 33/42 patients (79%) displayed anastomotic strictures in 17 patients (52%), bile duct stones in 8 (24%), both bile duct stones and an anastomotic stricture in 2 (6%), papillary stenosis in 1 (3%), and anastomotic biliary leakage in 1 (3%). In contrast, the contrastogram was normal in four patients (12%). Stone extraction was completed in 9/10 patients (90%) with a mean of 1.2 sessions, while stricture dilation was achieved in 12/19 patients (63%) after a mean of 1.7 sessions, by stent positioning (n = 7), balloon dilation (n = 4), or Soehendra dilator (n = 1). Both biliary leakage and papillary stenosis were cured by ERCP. Only one procedure-related complication -- severe pancreatitis (2.4%) -- was observed and no mortality., Conclusion: ERCP is a safe and effective mode of management of bile duct complications after OLT. It should be attempted before a surgical approach. Better results are obtained for treatment of biliary stones than of anastomotic strictures.

Free radicals play a central role in the development of liver ischemia/reperfusion (I/R) injury. Reduced glutathione (GSH) is the main hepatic free radical scavenger. Brain-dead patients exhibit abnormalities of endocrine status. Many clinicians administer thyroid hormones to improve the transplantation outcomes. We previously reported that thyroxine (T(4)) pretreatment decreased rat liver tissue GSH, which was associated with increased liver I/R-induced damage. In this study, we investigated whether the reduction in GSH by T(4) pretreatment affected cell viability during anoxia or oxidative stress in suspensions of isolated hepatocytes. Furthermore, we evaluated the levels of GSH in isolated livers from hypothyroid rats preserved at 0-1 degrees C and reperfused. Thyroid hormone modulation was obtained by T(4) or 6-propylthiouracil (PTU) treatment. Isolated hepatocytes from T(4)-pretreated rats that underwent anoxia and oxidative stress, which was induced by tert-butylhydroperoxide, displayed progressive, time-dependent loss of cell viability, which was greater than that in hepatocytes in non-T(4)-pretreated rats. A significant decrease in GSH levels was observed in isolated hepatocytes obtained from hyperthyroid rats compared with those from euthyroid rats. In contrast, administration of the antithyroid drug PTU increased liver concentrations of GSH at the end of reperfusion thereby improving liver function after cold storage. These results may yield new protective strategies in the management of brain-dead organ donors.

Unlabelled: Prioritization of patients on the waiting list (WL) for OLT is still a critical issue. Numerous models have been developed to predict mortality before and after OLT., Aim: The aim of the study was to prospectively evaluate cirrhotics with and without hepatocellular carcinoma (HCC) undergoing orthotopic liver transplantation (OLT) severity of liver disease on the WL and at transplant, mortality on the WL and after OLT, and their correlations., Materials and Methods: An algorithm based on seven patient variables (MELD, CTP, UNOS, HCC, BMI, waiting time, age) was created by software dedicated to prioritize patients on the waiting list., Results: We evaluated 118 patients including 75 men and 43 women of age range 19 to 66 years, who underwent OLT from July 2004 to June 2006. Mean CTP and MELD at listing were 8.44 (range 6-12) and 13 (range 2-24), respectively. Overall mortality on the WL at 24 months was 13%, which was significantly higher among patients with MELD > 25 compared to patients with MELD 0 to 15 (P < .0001) or MELD 16 to 25 (P = .0007) at listing. Mean MELD at OLT was 15 (range 7-36), which was significantly lower in patients with than without HCC (MELD 12 vs 16; P = .0003). Six hundred-day patient survival was significantly lower among patients with MELD > 25 compared to patients with MELD < 25 at OLT (P = .017), whereas no difference in survival was observed between patients with and without HCC., Conclusions: The sickest patients are characterized by high mortality both on the waiting list and after liver transplantation. Patients with HCC are transplanted in better condition compared to patients without HCC with the same survival.

Liver transplantation still represents the only effective treatment for patients with liver failure, but many patients die while awaiting transplantation, even though many attempts have been made to increase the organ procurement rates and to partially support hepatic function in recent years. Our aim was to design an "open" ex vivo perfused liver model to simplify liver support using an isolated porcine liver perfused with arterial and portal blood from the recipient pig, while monitoring the metabolic capacity of the supporting graft. It was possible to perfuse the isolated liver for 6 hours as a bridging procedure with satisfactory hemodynamic homeostasis controlled by software biofeedbacks.

Introduction: Liver transplantation represents the gold standard for the treatment of chronic liver disease. The whole transplantation process was assessed using an intention-to-treat analysis and considering patients from the time of their inclusion on the list and throughout lengthy follow-up., Materials and Methods: From January 1, 1999 to June 1, 2004, 373 adults joined the waiting list for liver transplantation at our institution. The main variables analyzed were: age, gender, etiology, Model for End-stage Liver Disease score, Child-Pugh class, United Network for Organ Sharing (UNOS) status. Global survival was evaluated using intention-to-treat analysis from the time of patient inclusion in the list to the end of their late follow-up., Results: The median waiting time was 20 months (range 0.1 to 70.2). By univariate analysis, the variables significantly influencing survival when patients joined the waiting list were: encephalopathy; ascites, poor nutritional status, Child-Pugh class C, UNOS 2, hepatitis C virus (HCV) and bilirubin > 2 mg/dL. By multivariate analysis, only HCV-related cirrhosis emerged as having an independent prognostic value. By intention-to-treat analysis, the 5-year survival rate was 67% and 79% for HCV-positive and HCV-negative patients, respectively (P = .0003)., Conclusions: HCV-related cirrhosis is an independent prognostic factor for survival according to an intention-to-treat analysis. Different inclusion criteria or treatments while on the waiting list and after transplantation need to be considered in the future for HCV-positive patients.

Background/aim: The main indications for combined liver and kidney transplantation (CLKT) are as follows: (1) cirrhosis with renal damage dependent or not upon liver disease, (2) renal failure with dialysis and concomitant liver end-stage disease, (3) congenital diseases, and (4) enzymatic liver deficiency with concomitant renal failure. The aim of this study was to evaluate our results with CLKT both in adult and pediatric patients., Methods: From September 1995 to September 2006, 15 CLKT (2.8%) among 541 liver transplantations included 4 pediatric patients (27%). The main indications for CLKT were hepatitis C virus (HCV) and polycystic diseases in adult patients, and primary hyperoxaluria in pediatric patients., Results: The double transplantation was performed from the same donor in all cases. All adult patients received whole liver grafts, whereas 3 split transplants and 1 whole liver graft were transplanted in the pediatric patients. Median liver and kidney cold ischemia times were 468 and 675 minutes, respectively. After a median follow-up of 36 months (range, 1-125), the overall survival rate was 80%. Five-year patient and graft survival rates were 100% for adult CLKT, whereas they were 50% for pediatric patients. We observed only 2 cases (18%) of delayed renal function, requiring temporary hemodialysis with progressive graft improvement. There was only 1 case of kidney retransplantation due to early graft nonfunction in a pediatric patient., Conclusion: Although CLKT is related to major surgical risks, results after transplantation are satisfactory with an evident immunological advantage.

Objective: The objective of this study was to analyze experience on pediatric liver transplantation (LT) between June 1993 and September 2006, including split liver transplantation (SLT), living donor liver transplantation (LDLT), and auxiliary partial orthotopic liver transplantation (APOLT). Furthermore, hepatocyte transplantation (HT) had a role in one patient with metabolic disease., Methods: From November 1990 to September 2006, 657 LTs were performed including 63 pediatric LTs (9.6%) in 57 patients (32 boys and 25 girls). Six were retransplantations (9.5%). Thirty-two patients (57%) were younger than 5 years. The types of graft included the following: 26 whole organs (41%), 32 in situ split organs (51%), 4 reduced-size organs (6%), and 1 graft from a living donor (2%). Two patients received an APOLT, 4 patients received a combined kidney-liver transplantation (CKLT), and 1 patient received HT. Of the 63 pediatric LTs, 16 were behaved to be highly urgent (25%)., Results: Overall 1-, 3-, 5-, and 10-year patient survival rates were 82%, 82%, 78%, and 78%, respectively. Overall 1-, 3-, 5-, and 10-year graft survival rates were 76%, 76%, 72%, and 72%, respectively. In patients younger than 1 year, the 5-year survival rate was 100%. Perioperative mortality was 8.8%. Vascular complications occurred in 4 patients (6.3%). Six children required retransplantation due to primary nonfunction (PNF) in 4 cases (7%) and vascular thrombosis in 2 cases (3.5%)., Conclusions: Cholestatic liver disease and age younger than 1 year were the best prognostic factors for excellent survival.

Bacterial contamination is one of the potential risks of blood salvage and reinfusion during orthotopic liver transplantation (OLT) because cell-saver machines lack antibacterial protection devices. This study was designed to analyze the potential bacterial contamination of blood salvaged during OLT; a secondary end point was to evaluate whether reinfusion of potentially contaminated blood may have been responsible for clinically manifested infective complications in the same patient. After induction of anesthesia, a blood sample was drawn from the central venous catheter (CVC) immediately after its positioning, to exclude potential coexisting hematic contamination of the recipient. During the procedure, 2 other samples of salvaged blood were collected for bacteriological analysis. Twenty-six of 38 samples of salvaged blood were positive for microorganisms, whereas 12 did not reveal the presence of infectious agents. In 19 of 26 positive samples, Staphylococcus species (73%) were isolated with only 2 of 38 samples drawn from CVC being contaminated. Candida Albicans was cultured in 2 samples. The high percentage (73%) of coagulase-negative Staphylococci indicates that blood contamination could have been caused by microorganisms from the air or suctioned from contact surfaces and the surgical field. Although almost 70% of processed and reinfused units tested positive for microbes, none of the postoperative blood cultures (at day 1 and day 3) revealed growth of the same species, not even in the 2 patients who had positive CVC cultures after induction of anesthesia.

Background/aims: The aim of this retrospective study is to analyze the prognostic impact of Model for End-Stage Liver Disease (MELD) score in patients undergoing liver transplantation (OLT) with suboptimal livers., Methods: Between January 2002 and January 2006, 160 adult patients with liver cirrhosis received a whole liver for primary OLT at our institution including 81 with a suboptimal liver (SOL group) versus 79 with an optimal liver (group OL). The definition of suboptimal liver was: one major criterion (age >60 years, steatosis >20%) or at least two minor criteria: sodium >155 mEq/L, Intensive Care Unit stay >7 days, dopamine >10 microg/kg/min, abnormal liver tests, and relevant hemodynamic instability., Results: Baseline recipients characteristics were comparable in the two study groups. The SOL group had a significantly greater number of early graft deaths (<30 days) than the OL group, while the 3-year Kaplan-Meier patient survivals were similar. Using logistic regression, MELD score was significantly related to patient death only in the SOL group (P = .01), and the receiver operator characteristics curve method identified 17 as the best MELD cutoff with the 3-year survival of 93% versus 85% for MELD < or =7 versus >17, respectively (P > 05). In comparison, it was 94% and 72% in the SOL group (P < .05). Similarly, MELD >17 was significantly associated with early graft death rates only in the SOL group., Conclusion: This study advised surgeons to not use suboptimal livers for patients with advanced MELD scores, thus supporting a donor-recipient matching policy.

Background: Hepatocellular carcinoma (HCC) competes with benign liver disease as indication for liver transplantation (OLT). The aim of this study was to determine long-term results of OLT for HCC., Methods: We retrospectively analyzed the prognostic role of HCC diagnosis at pathological exam in adult OLT. In the HCC group, we evaluated the prognostic role of the time of diagnosis (incidental versus nonincidental) and of pathological tumor TNM staging. The primary endpoint was 1-, 3-, and 10-year patient survivals., Results: From 1991 to 2006, among 550 adults who underwent first OLT, HCC was found in 120 patients at pathological exam. In 26 cases (22%), the diagnosis of HCC was incidental. There were 59 cases (49%) of pathological T1 to T2 tumor (one nodule < 5 cm, or two to three nodules < 3 cm, without metastases and/or vascular invasion), and 61 cases (51%) of pathologic T3-T4a tumor. HCC diagnosis did not show a significant prognostic impact by Cox survival analysis. After a median follow-up of 31 months, 1-, 5-, and 10-year survivals were 91%, 81%, and 73% in the HCC group, and 84%, 76%, and 67% in the non-HCC group. Time of HCC diagnosis (incidental versus nonincidental) and pathological TNM staging (T1 to T2 vs T3 to T4a) did not result significant survival predictors upon Cox analysis., Conclusion: In our experience, the long-term results of OLT for HCC overlapped those of OLT for benign disease, although 51% of tumors were T3 to T4a at pathological exam.

Unlabelled: Hypothermic machine perfusion (MP) of the liver has been reported to improve graft function reclaiming marginal livers, such as those from non-heart-beating donors. Livers from obese donors often have fatty infiltrates and are more susceptible to hypothermic conditions. No data exist about MP at temperatures >4 degrees C. This study evaluated liver function after organ preservation by comparing MP at 20 degrees C with conventional cold storage., Methods: For MP, rat livers were perfused for 6 hours using an oxygenated Krebs-Henseleit (KH) solution at 20 degrees C (pH 7.4). For cold storage, livers were perfused in situ and preserved with Celsior solution at 4 degrees C for 6 hours. The reperfusion period with KH (2 hours at 37 degrees C) was performed under the same conditions both among livers preserved by MP or cold storage. Hepatic enzyme release (aspartate aminotransferase [AST], alanine aminotransferase [ALT], lactate dehydrogenase [LDH], and gamma-glutamyl transferase [GGT]), bile production, and ATP levels were measured during MP and reperfusion., Results: At the end of reperfusion, livers preserved by MP showed significantly decreased liver damage compared with cold storage: AST, 18 +/- 4 vs. 45 +/- 6 mU/mL (P < .01); ALT, 1.5 +/- .07 vs. 6 +/- 0.5 mU/mL (P < .01); and LDH, 82 +/- 2 vs. 135 +/- 29 mU/mL (P < .05). No difference was observed between bile production between MP and cold storage. High levels of biliary GGT and LDH were found in cold preserved livers. ATP levels were higher in livers preserved with MP compared with those preserved by cold storage., Conclusions: MP at 20 degrees C resulted in a better quality of liver preservation, improving hepatocyte survival, compared with conventional cold storage. This may provide a new method for successful utilization of marginal livers, in particular fatty livers.

Choice of calcineurin inhibitor may be a contributing factor to deteriorating patient and graft survival following liver transplantation for hepatitis C virus (HCV). In our multicenter, open-label LIS2T study, de novo liver transplant patients stratified by HCV status were randomized to cyclosporine or tacrolimus. Follow-up data were obtained in an observational study of 95 patients. Mean follow-up was 34 and 37 months, respectively, for cyclosporine-treated (n = 47) and tacrolimus-treated (n = 48) patients. In patients not receiving antiviral therapy, 22 of 31 given cyclosporine (72%) and 24 of 29 given tacrolimus (83%) had biochemical recurrence of HCV. In 68 patients with at least one biopsy, histological evidence of HCV-related hepatitis was present in 27 of 31 (87%) cyclosporine-treated patients and 37 of 37 (100%) tacrolimus-treated patients (P = .02, chi-square test). Three-year actuarial risk of fibrosis stage 2 was 66% with cyclosporine and 90% with tacrolimus; for fibrosis stage 3 or 4 it was 46% and 80%, respectively. Three graft losses were attributed to HCV recurrence in cyclosporine-treated patients and six in tacrolimus-treated patients. Tacrolimus may be associated with increased risk of histological HCV disease recurrence compared to cyclosporine.

There is no controlled clinical trial on the treatment of de novo arterial hypertension after liver transplantation (LT) a common complication using calcineurin inhibitors (CNI) for immunosuppressive therapy. The aim of this study was to compare the efficacy and safety of nifedipine, a calcium channel blocker, and carvedilol, an alpha1- and beta-blocker. The study included 50 patients who developed arterial hypertension after LT. The data on the first 30 patients who have completed 12-month follow-up are reported herein. Eighteen patients received nifedipine, and 12 patients received carvedilol. Patients were evaluated monthly at the outpatient clinic for 1 year. If patients developed severe adverse effects to nifedipine, they were switched to carvedilol and vice versa (therapy failure). The two groups were similar for clinical features, indications for LT, immunosuppressive therapy, and baseline blood pressures. A failure of treatment was observed in 9 of 18 patients treated with nifedipine (50.0%) and one of 12 patients treated with carvedilol (8%, P < .025). Nifedipine was effective in 4 of 18 patients, carvedilol, in 4 of 12 patients (22.21% vs 33.3%, P = NS). Two of the nine nonresponders to nifedipine responded to carvedilol. The efficacy of monotherapy was observed in 11 of 40 randomized patients (27.5%). Carvedilol monotherapy is as effective as nifedipine but far better tolerated.

Introduction: Hepatoblastoma (HEP) is the most frequent liver malignancy occurring in childhood. Surgical resection currently represents the gold standard for treatment. In patients with initially unresectable tumors, chemotherapy may induce remarkable reductions in size. In nonresponder patients, liver transplantation (OLTx) may offer a chance of cure., Materials and Methods: From 1990 to 2003, a total of 400 OLTx (31 pediatric transplants) have been performed at Padua University. Seven patients (4 males and 3 females) underwent OLTx for hepatoblastoma. All patients presented with bilobar liver involvement and had received chemotherapy according to the SIOPEL-1. In all patients preoperative staging was negative for extrahepatic involvement., Results: The mean age of the pts was 8.2 years (range 6.4 months to 34 years). Mean follow-up after OLTx was 41.4 months (median 36, range 3 to 108 months). Actuarial patient survival rates after OLTx for hepatoblastoma are 83.3%, 83.3%, and 56% at 1, 3, and 5 years, respectively. Five of seven subjects with HEP are alive after transplant at 3, 12, 36, 65, and 108 months. Two patients died owing to recurrent disease after 6 and 60 months, respectively, from transplantation. Another subject, primarily treated with surgical resection, shows HEP recurrence at 40 months after OLTx. The remaining 4 patients are alive and well at a mean follow-up of 28 months (median 24, range 3 to 65 months)., Conclusions: Liver transplantation may represent a valid therapeutic option for patients with unresectable HEP, but it is contraindicated in cases of recurrence following previous resection surgery. Neo-adjuvant chemotherapy is of paramount importance to obtain good long-term results.

Introduction: Hepatocellular carcinoma (HCC) is one of the most common tumors worldwide. In the Western world the current epidemic of cirrhosis due to the hepatitis C virus (HCV) is increasing the number of new cases. Liver transplantation (OLTx) represents a radical treatment for HCC and the underlying cirrhosis. Whether adjuvant chemotherapy is indicated in the postoperative period to prevent recurrence is controversial., Material and Patients: Forty-eight HCC patients underwent liver transplantation during 11 years, including 21 who were chemo-treated (CT) patients. Thirty-one patients (65%) had post-necrotic virus-C cirrhosis (PNC-C). Twenty-one cases (44%) were p-TNM stages III-IV, and 15 cases (31%) incidental HCC detected in the explanted liver. Seven HCV patients (15%) received chemotherapy (before 1998)., Results: One-, 3-, and 5-year overall survival rates were 100%, 85%, 79% (CT group), and 89%, 71%, 71% (no CT group), respectively. The HCV recurrence-free survival rates at 3, 6, and 12 months were 29%, 14%, 0% for the CT group, versus 76%, 38%, 25% for the no CT group (P =.005)., Conclusions: Discontinuation of HCV-HCC patients by chemotherapeutic adjuvant protocols after transplantation appears rational due to the early hepatitis C recurrence confirmed in our series. Moreover, few studies have demonstrated that CT prolongs survival of HCC transplanted patients. New pharmacological approaches are necessary to solve these questions.

Unlabelled: The progressive increase in patients with end stage liver disease has lengthend the waiting- list for liver transplantation. Unfortunately this has not been followed by a suitable increase in the number of donors. The expanding "donor pool" has required use of "marginal" donors (ICU stay > 10 days, sepsi; steatosis > 30-40%, hypernatremia > 155 mmol/L, inotropic drugs). We report the case of a skier who remained for more than 1 hour in cardio-respiratory arrest under the snow; the 49-year-old women was extracted from the snow after 1 hour and 12 minutes and found to be asystolic, fixed pupils and deep hypothermia (27.2 degrees C). After cardiopulmonary resuscitation, partial cardio-respiratory activity was re-established. In the ICU severe hypothermia (26.7 degrees C) was treated with extracorporeal circulation until a re-establishment of satisfactory cardio-circulatory conditions was obtained. Unfortunately cerebral anoxic cerebral death was established and multiorgan procurement performed 3 days later. After liver transplantation into a 59 year-old patient with PNC-C was performed. The course was uneventful and the patient was discharged on the 19th postoperative day., Conclusions: Organ procurement from donors involved in accidental traumatic events with cardio-respiratory arrest and hypothermia, is similar to the non-heart-beating donor (NHBD) condition. Correct cardiopulmonary resuscitation and the use of extracorporeal circulation for gradual restoration of body temperature are necessary for optimal organ perfusion. In the present case the anoxic insult induced by the cessation of the cardio-respiratory function, was probably mitigated (if not even annulled) by the hypothermia.