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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.

In recent years, a worsening outcome of hepatitis C virus (HCV)-positive recipients and a faster progression of recurrent disease to overt cirrhosis has been reported. Our aims were to 1) assess patient survival and development of severe recurrent disease (Ishak fibrosis score > 3) in different transplant years; and 2) model the effects of pre- and post-liver transplantation (LT) variables on the severity of recurrent disease. A multicenter retrospective analysis was conducted on 502 consecutive HCV-positive transplant recipients between January 1990 and December 2002. Protocol liver biopsies were obtained at 1, 3, 5, 7, and 10 yr post-LT in almost 90% of the patients. All 502 patients were included in the overall survival analysis, while only the 354 patients with a follow-up longer than 1 yr were considered for the analysis of predictors of disease progression. The overall Kaplan-Meier survival rates were 78.7%, 66.3%, and 58.6%, at 12, 60, and 120 months, respectively, and a trend for a better patient survival over the years emerged from all 3 centers. The cumulative probability of developing HCV-related recurrent severe fibrosis (Ishak score 4-6) in the cohort of 354 patients who survived at least 1 yr remained unchanged over the years. Multivariate analysis indicated that older donors (P = 0.0001) and female gender of recipient (P = 0.02) were the 2 major risk factors for the development of severe recurrent disease, while the adoption of antilymphocytic preparations was associated with a less aggressive course (P = 0.03). Two of these prognostic factors, donor age and recipient gender, are easily available before LT and their combination showed an important synergy, such that a female recipient not only had a much higher probability of severe recurrent disease than a male recipient but her risk increased with the increasing age of the donor, reaching almost 100% when the age of the donor was 60 or older. In conclusion, a trend for a better patient survival was observed in more recent years but the cumulative probability of developing severe recurrent disease remained unchanged. The combination of a female recipient receiving an older graft emerged as a strong risk factor for a severe recurrence.

This prospective study analyzed the dropout probability and intention-to-treat survival rates of patients with hepatocellular carcinoma (HCC) selected and treated according to our policy before liver transplantation (LT), with particular attention to those exceeding the Milan criteria. Exclusion criteria for LT were macroscopic vascular invasion, metastases, and poorly differentiated disease at percutaneous biopsy. A specific multi-modal adjuvant algorithm was used to treat HCC before LT. A total of 100 HCC patients were listed for LT: 40 exceeded the Milan criteria in terms of nodule size and number (MILAN OUT) either at listing or in list, while 60 patients continued to meet the criteria (MILAN IN). The Milan criteria did not prove to be a significant predictor of dropout probability or survival rates using Cox's analysis. Cumulative dropout probability at 6 and 12 months was 0% and 4% for MILAN OUT, and 6% and 11% for MILAN IN. The intention-to-treat survival rates at 1 and 3 years were 95% and 85% in MILAN OUT, and 84% and 69% in MILAN IN. None of the 68 transplanted patients had recurrent HCC after a median 16-month follow-up (0-69 months). In conclusion, LT may be effective for selected, aggressively-treated HCC patients exceeding the Milan criteria.

Epstein-Barr virus (EBV) infection is the main cause of post-transplant lymphoproliferative disease (PTLD). Little is known on chronic carrier state and its relation with late PTLD. We aimed to study EBV infection in the long-term after paediatric liver transplantation (OLT). We conducted a retrospective review of 34 children monitored for a median of 5.8 years (range 1.5-17.7). 21 were IgG seronegative (group A) and 13 seropositive (group B) before OLT. Primary infection was the appearance of VCA-IgM or VCA-IgG or Real-Time Polymerase Chain Reaction (RT-PCR) in patients previously IgG seronegative; positive VCA-IgM or EA-IgG or RT-PCR lasting longer than 6 months was defined sustained viral detection (SVD). 18/21 patients of group A had a primary infection at a median time of 3 months after transplant (0.5-60). 14/18 of group A and 0/13 of group B had a SVD (P < 0.0001). Viral loads greater than 500 copies/10(5) mononuclear cells occurred in 12/18 patients in group A and 0/13 patients in group B (P < 0.0001). The 3 patients who developed late PTLD (median time after OLT 47 months, range 15-121) were from group A, and presented with SVD before developing PTLD. In conclusion, EBV infection in seronegative patients at OLT is associated with greater viral loads and sustained viral detection. Late PTLD occurred only in naïve patients with markers of SVD. Three to 4 monthly long-term monitoring of EBV in pre-OLT naïve patients might help preventing the occurrence of late PTLD., ((c) 2006 AASLD.)

Background: Partial hepatectomy (PH) and liver transplantation (LT) compete as first-line treatment for hepatocellular carcinoma (HCC). A prospectively collected database was retrospectively reviewed to establish when PH can compete with LT., Methods: Between 1991 and 2002, PH was performed in 131 cases of HCC (Child-Pugh A-B, technically resectable tumor without metastases). To ascertain patient survival after PH, we compared this series with a group of 40 HCC patients (G1-G2 HCC with no gross vascular invasion or metastasis) enlisted for liver transplantation during the same period., Results: The 1-, 3-, and 5-year intention-to-treat survival rates were 75%, 52%, and 31% for resection and 89%, 71%, and 63% for transplantation. Two tumor-related variables (gross vascular invasion and histological grade) and three liver function parameters (Child-Pugh score, bilirubin, Okuda stage) proved to be independent predictors of survival after resection, whereas nodule size and number, and Milan criteria did not. The 5-year survival of the best candidates for resection (favorable tumor biology with very well preserved liver function, n = 52) was 58%. On a descriptive basis alone, this result did not differ significantly from the outcome in LT patients. PH patients with a poorly differentiated tumor and/or gross vascular invasion (n = 28) had the worst outcome, irrespective of their liver function parameters., Conclusions: For technically resectable tumors without aggressive features (G3 or macroscopic vascular invasion), PH can only compete with LT, in terms of long-term survival, when patients with a well-preserved liver function are selected.

Objective: In cirrhosis, portal hemodynamics is usually considered independently of the disease etiology. The objective of this study was to investigate the role of the etiology of liver disease on the relationship between liver blood flow and liver pathology in endstage cirrhosis., Material and Methods: Portal blood velocity and volume, congestion index of the portal vein, and hepatic and splenic pulsatility indices were evaluated with echo-Doppler in cirrhotic patients immediately before liver transplantation. When a patent paraumbilical vein was present, its blood flow was measured and effective portal liver perfusion was calculated as portal blood flow minus paraumbilical blood flow. The hemodynamic parameters were correlated with liver weight and the pattern of the liver fibrosis morphometrically assessed in explanted livers. A total of 131 patients with alcoholic or viral cirrhosis were included in the study., Results: In alcoholic cirrhosis, liver weight was higher than that in viral disease (1246+/-295 g versus 1070+/-254 g, p=0.001), portal liver perfusion per gram of liver tissue was lower (0.49+/-0.36 ml g(-1) min(-1) versus 0.85+/-0.56 ml g(-1) min(-1), p=0.004) and hepatic pulsatility indices were higher (1.45+/-0.31 versus 1.26+/-0.30, p=0.018). The degree of liver fibrosis was similar in alcoholic and viral cirrhosis (11.7+/-5.5% versus 11.0+/-4.4%, p=NS). An inverse relationship between liver weight and Child-Pugh score was disclosed in viral (p<0.001) but not in alcoholic disease., Conclusions: A different hemodynamic pattern characterizes the advanced stage of cirrhosis of alcoholic and viral origin. A more severe alteration of intrahepatic portal perfusion, probably coexisting with a more severe hepatocyte dysfunction, and a higher liver weight can be detected in alcoholic cirrhosis.

Unlabelled: The aim of the study was to investigate the prevalence and clinical course of renal failure that was induced by the various types of bacterial infections in patients with cirrhosis and ascites. Three hundred and nine patients, who were consecutively admitted to the 3 major hospitals of Padova, Italy, during the first 6 months of 2005, were studied prospectively. Of these, 233 patients (75.4%) had evidence of ascites. In 104 patients with cirrhosis and ascites (44.6%) a bacterial infection was diagnosed. A bacterial infection-induced renal failure was observed in 35 of 104 patients (33.6%). The prevalence of renal failure was higher in biliary or gastrointestinal tract infections and in spontaneous bacterial peritonitis (SBP) and in than in other types of infections. In addition, the progressive form of renal failure was only precipitated by biliary or gastrointestinal tract infections, SBP, and urinary tract infections (UTI). In a multivariate analysis only MELD score (P = 0.001), the peak count of neutrophil leukocyte in blood (P = 0.04), and the lack of resolution of infection (P = 0.03) had an independent predictive value on the occurrence of renal failure., Conclusion: The results of the study show that the development of bacterial-induced renal failure in patients with cirrhosis and ascites is related to the MELD score, and to both the severity and the lack of resolution of the infection. A progressive form of renal failure occurs only as a consequence of biliary or gastrointestinal tract infections, SBP, and UTI.

Background: Radiofrequency thermal ablation is the first therapeutic option in percutaneous treatment of hepatocellular carcinoma but data on its long-term efficacy and safety are not conclusive., Aim: This study reports a prospective survey on radiofrequency thermal ablation in north-east Italy., Methods: Data were collected on 401 patients with hepatocellular carcinoma (males 301, mean age: 68 years) treated by radiofrequency thermal ablation in 13 centres. Indication to treatment was: single nodule not eligible for surgery in 77% of patients, 2-3 nodes in 18% and multiple lesions in 5%. Mean size was 3 cm (1-8 cm). Treatment response was assessed at 1 month by spiral computerized tomography and then with ultrasound examination and new spiral computerized tomography., Results: Complete response was obtained in 67% of patients and in 27% response was 75-99%. Complete response raised to 77% in lesions smaller than 3 cm. The morbidity rate was 34%; the mortality was 0.5%, seeding was observed in four patients. Ten patients presented an unexpected rapid disease progression., Conclusion: The above data show that by radiofrequency thermal ablation, complete response can be achieved only in about two-third of the cases, clearly less than expected, and that, beyond seeding, unexpected progression can be observed.

The metabolic activity of hepatocytes cultured on homologous acellular matrix (HAM) and transplanted into rats genetically incapable of bilirubin conjugation (Gunn rats) has been investigated. Hepatocytes from Wistar male rats were seeded on HAM and cultured for 9 days, and the proliferation rate and albumin mRNA expression were assayed daily. HAM alone or HAM plus hepatocytes (cultured for 3 days) were implanted in a subcutaneous pocket of the dorsal region of Gunn rats. No immunosuppression therapy was used. Blood samples were collected weekly and rats were sacrificed 10 weeks after surgery. Hepatocytes cultured on HAM displayed a higher proliferation rate than those cultured on plastic, and albumin mRNA expression was detected in hepatocytes seeded on HAM, but not on plastic. Serum bilirubin concentrations did not differ from baseline values in both the sham-operated control and HAM transplanted rats. On the contrary, in rats transplanted with HAM plus hepatocytes, circulating bilirubin levels decreased from week 4-7, and then plateaued until week 10. Histology did not evidence signs of rejection, but only a mild degree of inflammation around the implanted patches. It is concluded that hepatocytes seeded on HAM and transplanted into Gunn rats are able to metabolize bilirubin for at least two months, without signs of rejection even in the absence of immunosuppressive therapy.

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.

Objective: To report the results of a multicenter experience of split liver transplantation (SLT) with pediatric donors., Summary Background Data: There are no reports in the literature regarding pediatric liver splitting; further; the use of donors weighing <40 kg for SLT is currently not recommended., Methods: From 1997 to 2004, 43 conventional split liver procedures from donors aged <15 years were performed. Nineteen donors weighing < or =40 kg and 24 weighing >40 kg were used. Dimensional matching was based on donor-to-recipient weight ratio (DRWR) for left lateral segment (LLS) and on estimated graft-to-recipient weight ratio (eGRWR) for extended right grafts (ERG). In 3 cases, no recipient was found for an ERG. The celiac trunk was retained with the LLS in all but 1 case. Forty LLSs were transplanted into 39 children, while 39 ERGs were transplanted into 11 children and 28 adults., Results: Two-year patient and graft survival rates were not significantly different between recipients of donors < or =40 kg and >40 kg, between pediatric and adult recipients, and between recipients of LLSs and ERGs. Vascular complication rates were 12% in the < or =40 kg donor group and 6% in the >40 kg donor group (P = not significant). There were no differences in the incidence of other complications. Donor ICU stay >3 days and the use of an interposition arterial graft were associated with an increased risk of graft loss and arterial complications, respectively., Conclusions: Splitting of pediatric liver grafts is an effective strategy to increase organ availability, but a cautious evaluation of the use of donors < or =40 kg is necessary. Prolonged donor ICU stay is associated with poorer outcomes. The maintenance of the celiac trunk with LLS does not seem detrimental for right-sided grafts, whereas the use of interposition grafts for arterial reconstruction should be avoided.

The LIS2T study was an open-label, multicenter study in which recipients of a primary liver transplant were randomized to cyclosporine microemulsion (CsA-ME) (Neoral) (n = 250) (monitoring of blood concentration at 2 hours postdose) C2 or tacrolimus (n = 245) (monitoring of trough drug blood level [predose]) C0 to compare efficacy and safety at 3 and 6 months and to evaluate patient status at 12 months. All patients received steroids with or without azathioprine. At 12 months, 85% of CsA-ME patients and 86% of tacrolimus patients survived with a functioning graft (P not significant). Efficacy was similar in deceased- and living-donor recipients. Significantly fewer hepatitis C-positive patients died or lost their graft by 12 months with CsA-ME (5/88, 6%) than with tacrolimus (14/85, 16%) (P < 0.03). Recurrence of hepatitis C virus in liver grafts was similar in each group. Based on biopsies driven by clinical events, the mean time to histological diagnosis of hepatitis C virus recurrence was significantly longer with CsA-ME (100 +/- 50 days) than with tacrolimus (70 +/- 40 days) (P < 0.05). Median serum creatinine at 12 months was 106 mumol/L with CsA-ME and with tacrolimus. More patients who were nondiabetic at baseline received antihyperglycemic therapy in the tacrolimus group at 12 months (13% vs. 5%, P < 0.01). Of patients who were diabetic at baseline, more tacrolimus-treated individuals required anti-diabetic treatment at 12 months (70% vs. 49%, P = 0.02). Treatment for de novo or preexisting hypertension or hyperlipidemia was similar in both groups. In conclusion, the efficacy of CsA-ME monitored by blood concentration at 2 hours postdose and tacrolimus in liver transplant patients is equivalent to 12 months, and renal function is similar. More patients required antidiabetic therapy with tacrolimus regardless of diabetic status at baseline.

Background: Advanced biliary tract cancers have a poor prognosis. Gemcitabine (G) as a single agent or in combination represents an active treatment option. Systemic chemotherapy in hepatocellular carcinoma represents a palliative treatment. Gemcitabine in combination with Liposomal Doxorubicin (LD) may represent an active treatment option., Patients and Methods: Clinical trials for biliary and hepatic carcinoma have been reviewed., Results: We obtained RC (1 pt), RP (4 pts), SD (8 pts) and seven pts had PD (RR 25% and SD 40%). Our chemotherapy regimen was Gemcitabine 1000 mg/m(2) d 1 and 8, Liposomal Doxorubicin 30 mg d 1, q 28. Patients were 21 (17 M), aged 44 to 78 (median 63 yrs). Only in 8 pts we observed G 3-4 haematological toxicity, thrombocytopenia and neutropenia (7 G3, 1 G4).

Background/aims: The Barcelona Clinic Liver Cancer (BCLC) classification offers a prognostic stratification of patients with hepatocellular carcinoma (HCC). We recently demonstrated the BCLC's peculiar prognostic ability in a retrospective cohort of HCC patients. The aim of this study was to evaluate the BCLC system prospectively in a subsequent separate group of HCC patients enrolled at the same surgically oriented liver unit., Methods: One hundred and ninety-five consecutive HCC patients were prospectively enrolled and their liver disease was staged before therapy. Unlike the BCLC treatment protocol, nodule size and number were not used as absolute exclusion criteria for radical treatment. Predictors of survival were identified using the Cox model., Results: The median survival time was 23 months overall, and 53, 16, 7 and 3 months, respectively, for BCLC categories A, B, C, and D. In our cohort, BCLC had the best independent predictive power for survival when compared with the Okuda, CLIP, UNOS-TNM, and JIS prognostic systems (linear trend chi(2)=43.01, likelihood chi(2)=57.94, AIC 885.98). Moreover, the BCLC classification showed a better prognostic ability than the AJCC-TNM 2002 system in surgical patients., Conclusions: The discriminating power of BCLC staging was prospectively assessed in an Italian cohort of HCC patients treated mainly with radical therapies.

Aim: To evaluate the long-term histological outcome of patients transplanted for HBV-related liver disease and given HBIg prophylaxis indefinitely after LT., Methods: Forty-two consecutive patients transplanted for hepatitis B were prospectively studied. HBsAg, HBV-DNA and liver function tests were evaluated in the serum 3, 6 and 12 mo after LT and then yearly. LB was obtained 6 and 12 mo after LT and yearly thereafter. Chronic hepatitis (CH) B after LT was classified as minimal, mild, moderate or severe., Results: HBV recurred in 7/42 (16.6%) patients after 6-96 mo of follow-up. A hundred and eighty-seven LB were evaluated. Four of 7 patients with graft reinfection, all with unknown HBV DNA status before LT, developed cirrhosis at 12-36 mo of follow-up. Of the 122 LB obtained from 28 HBsAg+/HCV- recipients with no HBV recurrence after LT, all biopsies were completely normal in only 2 patients (7.1%), minimal/non-specific changes were observed in 18 (64.2%), and at least 1 biopsy showed CH in the remaining 8 (28.5%). Twenty-nine LB obtained from 7 patients transplanted for HBV-HCV cirrhosis and remaining HBsAg- after LT revealed recurrent CH-C. Actuarial survival was similar in patients with HBsAg+ or HBsAg- liver diseases., Conclusion: Though protocol biopsies may enable the detection of graft dysfunction at an early stage, the risk of progression and the clinical significance of these findings remains to be determined.

A specific split liver transplantation (SLT) program has been pursued in the North Italian Transplant program (NITp) since November 1997. After 5 yr, 1,449 liver transplants were performed in 7 transplant centers, using 1,304 cadaveric donors. Whole liver transplantation (WLT) and SLT were performed in 1,126 and 323 cases, respectively. SLTs were performed in situ as 147 left lateral segments (LLS), 154 right trisegment liver (RTL) grafts, and 22 modified split livers (MSL), used for couples of adult recipients. After a median posttransplant follow-up of 22 months, SLTs achieved a 3-yr patient and graft survival not significantly different from the entire series of transplants (79.4 and 72.2% vs. 80.6 and 74.9%, respectively). Recipients receiving a WLT or a LLS showed significantly better outcomes than patients receiving RTL and MSL (P < 0.03 for patients and P < 0.04 for graft survival). At the multivariate analysis, donor age of >60 yr, RTL transplant, <50 annual transplants volume, urgent transplantation (United Network for Organ Sharing (UNOS) status I and IIA), ischemia time of >7 hours, and retransplantation were factors independently related to graft failure and to significantly worst patient survival. Right grafts procured from RTL and either split procured as MSL had a similar outcome of marginal whole livers. In conclusion, in 5 yr, the increased number of pediatric transplants due to split liver donation reduced to 3% the in-list children mortality, and a decrease in the adult patient dropout rate from 27.2 to 16.2% was observed. Such results justify a more widespread adoption of SLT protocols, organizational difficulties not being a limit for the application of such technique., (Copyright 2006 AASLD)

Background: Intravenous administration of a third-generation cephalosporin is optimal antibiotic treatment for spontaneous bacterial peritonitis., Aims: To compare an intravenous-oral step-down schedule with ciprofloxacin (switch therapy) to intravenous ceftazidime in the treatment of spontaneous bacterial peritonitis, and to evaluate the impact of terlipressin and albumin in the treatment of type 1 hepatorenal syndrome on mortality., Methods: A total of 116 cirrhotic patients with spontaneous bacterial peritonitis, were randomly given switch therapy with ciprofloxacin (61 patients) or intravenous ceftazidime (55 patients). All patients who developed type 1 hepatorenal syndrome were treated with terlipressin (2-12 mg/day) and albumin (20-40 g/day)., Results: Resolution of infection was achieved in 46/55 patients treated with ceftazidime (84%) and in 49/61 patients treated with ciprofloxacin (80%, P = N.S.). An intravenous-oral step-down schedule was possible in 50/61 patients (82%) who received ciprofloxacin; 45/61 patients (74%) were discharged before the end of antibiotic treatment and completed it at home. The mean saving per patient due to the reduction of hospital stay in the ciprofloxacin group was 1150 . Type 1 hepatorenal syndrome was treated successfully in 12/19 patients (63%). As a consequence, the in-hospital mortality rate due to infection was 10%., Conclusions: Switch therapy with cephalosporin is more cost-effective than intravenous ceftazidime in the treatment of spontaneous bacterial peritonitis in cirrhotic patients who are not on prophylaxis with quinolones.

Aim: To explore the potential prognostic role of preoperative tumor grade and blood AFP mRNA in a cohort of patients with hepatocellular carcinoma (HCC) eligible for radical therapies according to a well-defined treatment algorithm not including nodule size and number as absolute selection criteria., Methods: Fifty patients with a diagnosis of HCC were prospectively enrolled in the study. Inclusion criteria were: (1) histological assessment of tumor grade by means of percutaneous biopsies; (2) determination of AFP mRNA status in the blood; (3) patient's eligibility for radical therapies., Results: At preoperative evaluation, 54% of the study group had a well-differentiated HCC, 42% had AFP mRNA in the blood, 40% had a tumor larger than 5 cm and 56% had more than one nodule. Surgery (resection or liver transplantation) was performed in 29 patients, while 21 had percutaneous ablation procedures. After a median follow-up of 28 mo, 12-, 24-, and 36-mo survival rates were 78%, 58%, and 51%, respectively. Surgical therapy, performance status and three tumor-related variables (AFP mRNA, HCC grade and gross vascular invasion) resulted as significant survival predictors at univariate analysis. Nodule size and number did not perform as significant prognosticators. Multivariate study selected only surgical therapy and a biologically early HCC profile (AFP mRNA negative and well-differentiated tumor without gross vascular invasion) as independent survival variables., Conclusion: The preoperative determination of tumor grade and blood AFP mRNA status may potentially refine the prognostic evaluation of HCC patients and improve the selection process for radical therapies.

A retrospective data analysis on liver transplantation for Wilson's disease (WD) was performed among Italian Liver Transplant Centers. Thirty-seven cases were identified. The main indication for liver transplantation was chronic advanced liver disease in 78% of patients. Mixed hepatic and neuropsychiatric symptoms were recorded in 32.3%. Eight patients presented with fulminant liver failure; 44.8% were on medical treatment. Patient and graft survival at 3 months, 12 months, 3 years, 5 years, and 10 years after transplantation were, respectively, 91.8%, 89.1%, 82.9%, 75.6%, and 58.8%, and 85.3%, 83.0%, 77.1%, 70.3%, and 47.2%. Neurological symptoms significantly improved after orthotopic liver transplantation (OLT), but the survival of patients with mixed hepatic and neuropsychiatric involvement was significantly lower than in patients with liver disease alone (P = 0.04). WD characterized by hepatic involvement alone is a rare but good indication for liver transplantation when specific medical therapy fails. Patients with neuropsychiatric signs have a significantly shorter survival even though liver transplantation has a positive impact on neurological symptoms. In conclusion, a combination of hepatic and neuropsychiatric conditions deserves careful neurological evaluation, which should contraindicate OLT in case of severe neurological impairment.

A 22-year-old Caucasian patient underwent living-donor liver transplantation (LDLT) for hepatic hemangioendothelioma in a healthy liver. The organ donor was his monozygotic twin brother. Surgery was uneventful in both donor and recipient, who received the same postoperative treatment (i.e. no immunosuppression for the recipient). Although both donor and recipient achieved a full liver function recovery, the volume of the recipient's graft increased much more than the donor's residual liver in the first postoperative month (1.6-fold vs. 1.2-fold). This different growth rate correlated with growth hormone (GH)/insulin growth factor (IGF) axis dynamics: the donor had significantly lower insulin-like growth factor 1 (IGF-1), insulin-like growth factor 2 (IGF-2) and insulin-like growth factor binding protein 3 (IGFBP-3) values than the recipient on postoperative days (POD) 3-30, although they had similar GH values. Other potential regenerative factors, e.g. tumor necrosis alpha, interleukin 6 (IL-6), insulin and C peptide did not correlate with liver regeneration rate. The particular endocrine picture of the graft may be explained by a modified GH-hepatocyte interaction due to cold ischemia during preservation resulting in a higher IGF production. Whether this is a potential molecular tool by means of which transplanted partial livers promote their regeneration remains to be seen in a larger number of patients.

Background: This study aimed to evaluate the incidence of cystadenoma diagnosis in a series of laparoscopic treatments for nonparasitic liver cysts, as well as its management., Methods: From 1996 to 2004, 26 patients with a nonparasitic cyst of the liver were selected for laparoscopic liver surgery. Solitary nonparasitic liver cysts were, whenever feasible, completely enucleated., Results: In four patients, the histopathologic examination showed a cystadenoma. Three patients with 13, 9, and 12-cm cysts, respectively, had undergone complete enucleation of the lesion, with no evidence of recurrence in the follow-up visit. One patient with multicystic liver experienced a recurrence and required an open hepatic resection., Conclusions: When a complete laparoscopic enucleation of the cyst can be ensured, a strict follow-up assessment should be considered as the definitive treatment, with surgical intervention demanded only in the case of recurrence or high suspicion for malignancy.

Background: Outcomes of split-liver transplantation (SLT) with pediatric donors have never been specifically reported., Methods: A prospective multicenter study on SLT using donors younger than 15 years was conducted. Thirty-nine split-liver procedures generating a left lateral segment (LLS) and an extended right graft (ERG) were performed. In three cases, no recipient was found for ERG. In all but one case, the celiac trunk was maintained with LLS. Data were available for 67 grafts (90% of the total): 38 LLSs and 9 ERGs transplanted into 46 children and 20 ERGs transplanted into 20 adults. Sixty-two (93%) grafts were used for primary transplants and five (7%) for retransplantation. SLT were performed with 15 donors 10 years of age and less and with 24 between 11 and 15 years., Results: Median follow-up was 24 months. Two-year patient and graft survival were 87% and 82%. Patient and graft survivals were not significantly different between pediatric and adult recipients, between recipients from donors 10 years of age and less and those between 11 and 15 years, and between recipients of LLS and ERG. Arterial complications occurred in 6% of cases (8% in the < or = 10 year donors group, 5% in the 11-15 year donors group). The incidence of other complications was similar between groups., Conclusions: SLT with pediatric donors, even younger than 10 years, provided results comparable with those achievable using adult donors. The similar incidence of arterial complications among patients receiving LLS or ERG suggests that maintenance of the celiac trunk with LLS is not detrimental for right-sided grafts.

Objectives: We report a female patient suffering from Takayasu arteritis (TA) who underwent surgical revascularization., Methods: By studying specimens obtained at surgery, we evaluated the cell composition of the arterial wall, along with the maturation pattern of vascular smooth muscle cells (VSMC) during the active phase of TA. Using TUNEL, we detected apoptotic cells within the tunica media., Results: The highest percentage of apoptotic cells was found in areas where inflammatory infiltrate was present and the medial structure was more or less damaged. Apoptotic cells were also found in structurally preserved areas, where VSMC but not inflammatory cells were present., Conclusions: Apoptosis involved not only inflammatory cells but also VSMC, particularly those of the immature type. We hypothesize a role for VSMC apoptosis in the development of TA.

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.

Background: : The use of orthotopic liver transplantation (OLT) for the treatment of patients with hepatocellular carcinoma (HCC) remains controversial because of the risk of both exclusion from the waiting list due to tumor progression and post OLT HCC recurrence. The aim of the present study was to evaluate the effect of an aggressive HCC treatment during the waiting list time on overall and recurrence-free survival of HCC transplanted patients in a single institutional study., Methods: : Since 1991, 40 HCC patients joined the OLT-waiting list. Poorly differentiated HCC cases were excluded, while size and number of nodules were not considered as absolute selection criteria. In all, 90% of the study group had HCC treatment while on the waiting list (transarterial chemoembolization, percutaneous therapies, chemotherapy)., Results: : Only one patient (2.5%) was removed from the waiting list after developing neoplastic portal thrombosis 3 months after listing, while 33 (82.5%) underwent to OLT after a median waiting list time of 11 months (range 3-16 months). On histological examination, 42% of the group did not meet the "Milan criteria" and 42% were pTNM stages III and IV. The median follow-up was 42 months. The 5-year actuarial survival rate was 64% and recurrence-free survival was 91%. HCC recurred in only two patients (6%)., Conclusions: : The use of routine pre-OLT tumor grading and of an aggressive HCC treatment during the waiting list, in our experience, resulted in a very low risk of pre OLT tumor progression leading to exclusion and of post OLT HCC recurrence.

Pregnancy is often successful after liver transplantation, despite the potentially toxic effects of immunosuppressive drug therapy. Liver transplant recipients with recurrent hepatitis C or hepatitis B nonetheless appear to be at risk of a worse graft function in the event of pregnancy, and antiviral drugs are generally contraindicated in pregnancy because of their teratogenic effects. A 33-year-old woman had undergone liver transplantation for Caroli's disease 6 years previously. Two years later the patient experienced de novo HBV hepatitis. Lamivudine treatment (100 mg/day) was started and clearance of HBsAg was documented 1 year later. Four years after starting antiviral treatment the patient became pregnant, despite of the risk of teratogenic effects; lamivudine, cyclosporine and azathioprine were not discontinued for risk of break-through hepatitis and acute or chronic rejection. The course of gestation was uneventful and caesarean section was performed after 36 weeks. The newborn infant was a healthy male weighing 3,080 g and measuring 50 cm.

We report the first case of auxiliary partial orthotopic liver transplantation (APOLT) in a patient with isoniazid (INH)-related fulminant hepatic failure (FHF) with the aim to determine the ability of the native liver (NL) to recover after this particular toxic event. A 10-year-old boy with INH-related FHF underwent APOLT after left hepatectomy on the NL. Neurological status and liver function rapidly improved, but, on postoperative day 22, urgent re-transplantation was needed for graft-hepatic artery thrombosis (HAT) and the NL's incapacity to sustain adequate liver function. Histological examination of the NL showed signs evident of its regeneration, however. In conclusion, though we faced the clinical failure of the NL functionally to sustain the patient in the presence of the graft HAT 3, weeks after APOLT, such a failure may be interpreted as time related. In fact, the histological picture in this particular case may suggest the potential for NL recovery after INH-related FHF.

Biliary cystadenoma is a very rare hepatic neoplasm, accounting for fewer than 5% of cystic neoplasms of the liver; regardless of the various diagnostic modalities, such a lesion may be difficult to distinguish preoperatively from a cystadenocarcinoma. Although a diagnosis of cystadenoma during open hepatic surgery demands a complete surgical resection, there are few reports describing the correct approach to such lesions after a laparoscopic approach. This article presents the first case series of incidental cystadenoma after laparoscopic surgery for hepatic cystic lesions. One patient with a polycystic liver disease treated with a laparoscopic enucleation of the larger cyst declined the reintervention after the diagnosis of cystadenoma; she had no recurrence at follow-up. One patient with a large simple hepatic cyst laparoscopically enucleated had no recurrence at the 18-month follow-up. In one patient, there was a high suspicion of recurrence of cystadenoma after the laparoscopic fenestration of a large cyst, but a histopathological specimen obtained after the open surgical resection could not confirm any signs of cystadenoma. The incidental finding of biliary cystadenoma after laparoscopic fenestration of a cystic hepatic lesion requires an open hepatic resection. When a complete laparoscopic enucleation of the cyst may be assured, a strict clinical, biochemical, and radiologic follow-up could be considered as the definitive treatment, demanding the surgical intervention only in case of recurrence or high suspicion for malignancy.

Background: It has previously been shown that bone mineral density (BMD) during the first year after orthotopic liver transplantation (OLT) in children with osteodystrophy increases remarkably and according to height. The effect of posttransplant factors possibly influencing bone mass in the long-term after a successful OLT in children is unknown., Methods: Eighteen patients (9 male), median age 13.3 (range 4.7-23.7) years, median time after OLT 8.3 (1.1-17.3) years were enrolled. Indications for OLT were biliary atresia (8), Alagille (3), hepatoblastoma (2), NonA-NonG acute liver failure (2), intrahepatic cholestasis, cryptogenic cirrhosis, and cholesteryl-ester disease (1 each). At OLT, all were prepubertal and 12 were severely cholestatic. We recorded anthropometric data, immunosuppression, dual-energy x-ray absorptiometry (DXA), biochemical markers of bone metabolism, and liver function., Results: Six children were on steroid therapy, eight were on cyclosporine, nine on tacrolimus. Median L1 to L4 spinal BMD was 0.720 (range 0.524-1.127) g/cm3, Z score -0.70 (-2.2- +2.1), height Z score -0.31 (-1.83- +1.96). Median bone mineral apparent density was 0.112 (0.084-0.142) (normal value 0.10-0.14) g/cm3. Median alanine aminotransferase level was 22 (range 11-79) IU/L, urinary free deoxypyridinolines 20.6 (7.1-62) nmol/mmol creatinine, osteocalcin 14 (2.3-45) microg/L, parathyroid hormone 51 (2-87) ng/L, Vitamin D3 67 (17-102) nmol/L., Conclusion: BMD after the first year from a successful pediatric liver transplantation is normal. Our study suggests that normal bone density in this setting is maintained for at least 1 decade.

Background: Alpha-fetoprotein (AFP) messenger RNA (mRNA) in the blood reflects the presence of circulating hepatocellular carcinoma (HCC) cells and is a sensitive marker of HCC extrahepatic metastases. The specificity of this molecular marker and its correlation with the main HCC clinical-pathological parameters remains controversial, however., Methods: AFPmRNA was determined in 50 HCC patients and in 50 patients with diagnosis of cirrhosis (6), or colon (24) or, pancreatic (20) carcinoma. HCC patients with clinically evident extrahepatic metastasis were excluded. HCC diagnosis was confirmed in all patients by histology on percutaneous biopsies or surgical specimens; pathological grading was assessed at the same time., Results: AFPmRNA was positive in 20 HCC patients (40%) and in 18 patients without HCC (36%). The presence of AFPmRNA in the blood correlated significantly with cholestatic indices (p<0.01), nodule size (p=0.03), vascular invasion (p=0.006) and moderately or poorly differentiated HCC (p<0.0001). Moreover, survival analysis showed a significant impact of AFPmRNA detection on overall (p=0.04) and recurrence-free survival (p=0.0007) after a median follow-up of 17 months., Conclusions: Although AFPmRNA is frequently detected in the blood, even in benign liver diseases or gastroenteric tumors, in HCC patients without clinical evidence of extrahepatic metastases it seemed to identify the biologically more aggressive tumors.

Background: Viaspan (University of Wisconsin [UW]) solution is the gold standard for abdominal organ preservation. Celsior (CEL) is an extracellular-type, low-potassium, low-viscosity solution, initially used for heart and lung preservation. We have performed a prospective multicenter study to compare the role of these cold-storage solutions on kidney and liver recovery after transplantation., Patients and Methods: From March 15, 2000 to December 31, 2001, 441 (172 CEL and 269 UW) renal transplants (RT) and 175 (79 CEL and 96 UW) liver transplants (LT) were included in the study., Results: Perfusate volume used was significantly lower in the UW group, being 4,732 +/- 796 mL versus 5,826 + 834 mL in the CEL group (P < 0.001). In LT, median total bilirubin serum levels were significantly higher at 5 and 7 posttransplant days in the UW group (90.6 and 92.3 micromol/L, respectively) as compared with CEL (51.3 and 63.4 micromol/L, respectively). After LT, primary nonfunction (PNF) rates in the CEL and UW groups were 3.8% and 4.2% (P = NS) respectively, with 1-year graft and patient survival being 83.3% versus 85.4% (P = NS) and 89.9% versus 90.6% (P = NS). After RT, delayed graft function (DGF) rates were 23.2% and 22.7% (P = NS), respectively; PNF rates were 1.9% and 1.7% (P = NS) respectively, with 1-year graft and patient survival being 92.3% versus 94.2% (P = NS) and 99.4% versus 97.7% (P = NS)., Conclusions: CEL solution was shown to be as effective as UW in both liver and kidney preservation. In LT patients, biliary function recovery is significantly better in the CEL group. CEL solution represents an efficacious option in multiorgan harvesting.

Many studies on cirrhotic patients have shown that insulin-like growth factor 1 (IGF-1) plasma levels are related to the severity of liver dysfunction. This result suggests that IGF-1 is probably useful for monitoring liver function in the perioperative course of orthotopic liver transplantation (OLT). Growth hormone (GH), IGF-1 plasma levels, and routine liver function tests were measured in 15 adult cirrhotic patients undergoing OLT. Measurements were made at the beginning of the operation; during OLT; 24 hours after reperfusion; and in the morning on days 7, 30, and 90. Twenty age-matched healthy volunteers with normal liver function served as controls. The study group had significantly higher GH levels and lower IGF-1 levels in the preoperative period compared with the controls. All patients achieved a complete functional hepatic recovery 1 month after OLT, although in 6 of them, the graft had an initial poor function (Group-IPF). GH and IGF-1 levels achieved near normal range within 1 week after OLT, and they had no significant correlations with other routine biochemistry tests in this period. IGF-1 levels in Group-IPF rose more slowly than in the group with a normal recovery of graft function. Surprisingly, 24 hours after reperfusion, IGF-1 levels were higher in Group-IPF than in the group with normal graft function. In conclusion, the severe GH/IGF-1 axis impairment found in patients with end-stage cirrhosis reverted very rapidly in the first days after successful OLT. Such a quick, postoperative modulation of IGF-1 plasma level by the graft suggests that this hormone has the potential to become one of the early indicators of post-OLT liver function recovery.

Severe liver dysfunction in late pregnancy is an unusual but dramatic event because it can progress very rapidly to fulminating disease and also because two lives, that of the mother and foetus, are involved. We report a descriptive study of a pregnant woman presenting with severe liver dysfunction.

Objective: To determine the long-term results of liver transplantation for well- or moderately differentiated hepatocellular carcinoma (HCC)., Summary Background Data: HCC patient selection for liver transplantation remains controversial, and deciding exclusively on the strength of criteria such as number and size of nodules appears prognostically inaccurate., Methods: Since 1991, preoperative tumor grading has been used at our center to establish whether a patient with HCC is fit for transplantation. Poorly differentiated HCC cases were excluded, while size and number of nodules were not considered as absolute selection criteria. Thirty-three patients with moderately or well-differentiated HCC were prospectively studied after liver transplantation. A group of 15 patients with incidental HCC transplanted during the same period were also evaluated and compared with the 33 patients with preoperatively diagnosed HCC., Results: On histologic examination, 38% of the entire group of 48 patients did not meet the "Milan criteria" and 42% were pTNM stages III and IV. The median follow-up was 44 months. The 5-year actuarial survival rate was 75% and recurrence-free survival was 92%. HCC recurred in only 3 patients (6%). The only histomorphologic variable differing significantly between incidental and nonincidental HCC was nodule size. The timing of diagnosis (incidental vs. nonincidental HCC), the Milan criteria, and the TNM stage revealed no statistically significant impact on overall and recurrence-free survival rates., Conclusions: The routine pre-orthotopic liver transplantation tumor grading may represent a valid tool in the selection of unresectable HCC patients for transplantation.

Background/aims: Prognosis assessment in patients with hepatocellular carcinoma (HCC) remains controversial. The most widely used HCC prognostic tool is the Okuda classification, but new staging systems (Cancer of the Liver Italian Program score, Chinese University Prognostic Index, French classification and Barcelona Clinic Liver Cancer, BCLC, staging) have been recently described. We investigated the value of known prognostic systems in the particular setting of a surgically oriented Liver Unit where 187 HCC Italian patients were mainly treated with radical therapies (resection and percutaneous ablation)., Methods: A retrospective analysis of 187 HCCs observed at a single Institution from 1990 and 1999 was performed. By using survival time as the only outcome measure (Kaplan-Meier method and Cox regression), the performance of any prognostic system was assessed according the criteria of discriminatory and stratification abilities between different stages, homogeneity of survival within each stage and additional explanatory power respect to the other classifications., Results: In the particular cohort studied, BCLC proved the best HCC prognostic system. This was true for the whole study group and for the 2 subgroups of surgical and non-surgical patients., Conclusions: BCLC staging showed the best interpretation of the survival distribution in an HCC population comprising a large proportion of tumors treated with potentially radical therapies.

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.

Background: There are few studies evaluating the prognostic impact on survival of treatment strategy in patients with hepatocellular carcinoma (HCC). The aim of this study was to analyse whether a multimodal approach, that represents a synergic association of different therapeutic procedures, may improve survival of patients with HCC., Patients and Methods: Two hundred and fourteen patients with HCC were enrolled in the study. The multimodal approach was chosen for 27 out of 106 (25%) non surgical patients, 42 out of 81 (52%) patients who underwent liver resection and 19 out of 27 (70%) patients who underwent liver transplantation., Results: The long-term survival of patients who underwent the multimodal approach improved significantly with respect to patients treated by both resection and other therapies alone. The 5-year survival rates were 52% vs. 11% (p < 0.05) in the non surgical group and 40% vs. 24% (p < 0.05) in the resection group when a multimodal approach was used for the treatment of recurrences. In patients with advanced HCC undergoing liver transplantation, multimodal treatment resulted in long-term survival comparable to that of patients with early HCC., Conclusion: A multimodal approach should be suggested in all patients with HCC, since a careful integration of surgical and non surgical treatments may improve long-term survival in such patients.

Primary dysfunction (PDF) still occurs after orthotopic liver transplantation (OLT). Celsior solution (CS) might offer some advantages over the conventional University of Wisconsin (UW) solution for organ preservation, but to date, this has not been prospectively evaluated in the context of OLT. In this prospective, randomized, multicenter, pilot study, 215 potential liver donors were enrolled and randomized. In 42 cases, the livers were unsuitable for transplantation; therefore, 173 randomized livers ultimately were implanted after perfusion and cold preservation with CS (n = 83) or UW solution (n = 90). In accord with the indications of the CS manufacturing company, total CS infusion volume was 90 mL/kg, greater than that of UW solution (60 mL/kg). The main aim of the study is to compare the prevalence of PDF between the two groups. Donor and recipient variables were similar in the two groups. Episodes of PDF were numerically lower in the CS (2.4%) than UW group (7.8%), but the difference was not statistically significant. There was a trend toward a lesser need for early re-OLT (<30 days) in the CS group (P =.0507), but again, no statistically significant difference emerged. Overall and time-differentiated postoperative deaths also were similar. One-year actuarial patient (UW, 89% v CS, 87%) and graft (UW, 83% v CS, 85%) survival rates were similar. In conclusion, CS was similar to UW solution as a preservation solution in the clinical setting of OLT at the infusion volumes described, although some theoretical advantages of CS composition suggest that CS might prove a valid alternative to UW preservation solution in multiorgan harvesting, including the liver. A study on a larger patient basis is needed.

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.

Background: The authors present their experience in the laparoscopic management of hepatic cysts and polycystic liver disease (PLD)., Methods: Between January 1996 and January 2002, 16 patients underwent laparoscopic liver surgery. Indications were solitary giant cysts (n = 10) and PLD (n = 6). Data were collected retrospectively., Results: Laparoscopic fenestration was completed in 15 patients. Median operative time was 80 min. There was no deaths. Complications occurred in four patients: one patient with a solitary liver cyst experienced diarrhea, while a pleural effusion, a bleeding from the trocar-insertion site, and ascites occurred in three patients with PLD. Median follow-up was 34 months. There was one asymptomatic recurrence (11%) in one patient with a solitary cyst. Two patients with PLD had a symptomatic recurrence of a liver cyst., Conclusion: Laparoscopic fenestration could be the preferred treatment of solitary liver cysts and PLD. Adequate selection of patients and type of cystic liver together with a meticulous surgical technique are recommended.

Therapeutic options for blunt hepatic trauma include both non-operative and operative management. We have reviewed our experience of the management of blunt hepatic trauma, from non-operative to liver transplantation. A total of 72 patients with blunt hepatic injury observed at the first surgical unit of Padua in a 3-year period (1998-2000) were analysed; we also included a patient who had a liver transplant in 1993 for severe liver trauma. Twenty-nine patients (39.7%) were treated conservatively, with a 93% success rate; 60.3% were treated surgically. Suture hepatorraphy was the most common procedure performed (52.3%). Advantages of non-operative management in our experience were the reduced need for transfusion (1.1U versus 4.3U) with 92% of patients not needing transfusion, and a reduced stay in the intensive care unit; there was no liver-related mortality. The overall morbidity in surgical patients was 30%, with 16% liver-related complications. Twelve surgical patients (27.2%) died, with a liver-related mortality of 18.2%. A large number of patients may present with an associated endo-abdominal injury, even in low-grade liver trauma, requiring rapid laparotomy. In high-grade hepatic trauma, the evolution toward liver failure is an indication for liver transplantation.