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Background: To generate a robust predictive model of Early (3 months) Graft Loss after liver transplantation, we used a Bayesian approach to combine evidence from a prospective European cohort (Liver-Match) and the United Network for Organ Sharing registry. Methods: Liver-Match included 1480 consecutive primary liver transplants performed from 2007 to 2009 and the United Network for Organ Sharing a time-matched series of 9740 transplants. There were 173 and 706 Early Graft Loss, respectively. Multivariate analysis identified as significant predictors of Early Graft Loss: donor age, donation after cardiac death, cold ischaemia time, donor body mass index and height, recipient creatinine, bilirubin, disease aetiology, prior upper abdominal surgery and portal thrombosis. Results: A Bayesian Cox model was fitted to Liver-Match data using the United Network for Organ Sharing findings as prior information, allowing to generate an Early Graft Loss-Donor Risk Index and an Early Graft Loss-Recipient Risk Index. A Donor-Recipient Allocation Model, obtained by adding Early Graft Loss-Donor Risk Index to Early Graft Loss-Recipient Risk Index, was then validated in a distinct United Network for Organ Sharing (year 2010) cohort including 2964 transplants. Donor-Recipient Allocation Model updating using the independent Turin Transplant Centre dataset, allowed to predict Early Graft Loss with good accuracy (c-statistic: 0.76). Conclusion: Donor-Recipient Allocation Model allows a reliable donor and recipient-based Early Graft Loss prediction. The Bayesian approach permits to adapt the original Donor-Recipient Allocation Model by incorporating evidence from other cohorts, resulting in significantly improved predictive capability. © 2013 Editrice Gastroenterologica Italiana S.r.l.

s / Digestive and Liver Disease 46 (2014) e71–e84 e73 QUANTIFICATION OF TACROLIMUS IN PBMCS SAMPLES IN PEDIATRIC LIVER TRANSPLANT PATIENTS AND CORRELATION WITH TACROLIMUS WHOLE BLOOD CONCENTRATION Michele Pinon1,∗, Pier Luigi Calvo1, Antonio D’Avolio2, Debora Pensi2, Andrea Brunati3, Roberto Canaparo4, Amedeo De Nicolo2, Giulia Carbonaro3, Alessia Cerrina3, Giovanni Di Perri2, Renato Romagnoli3, Cristiana Barbera1, Mauro Salizzoni3 1 Department of Pediatric Gastroenterology and Hepatology, Regina Margherita Children’s Hospital, Azienda Ospedaliera Citta della Salute e della Scienza, University of Turin, Turin, Italy 2 Unit of Infectious Diseases, University of Turin, Department of Medical Sciences, Amedeo di Savoia Hospital, Turin, Italy 3 Liver Transplantation Center, Azienda Ospedaliera Citta della Salute e della Scienza, University of Turin, Turin, Italy 4 Department of Drug Science and Technology, University of Turin, Turin, Italy Objective: Therapeutic drug monitoring (TDM) of tacrolimus in whole blood is essential to optimize clinical outcomes and reduce toxicity. However, the relationship between blood concentrations and therapeutic efficacy is unclear, probably because it does not reflect tacrolimus concentration at the active site. In this preliminary study, our aims were to validate a newmethod for tacrolimus quantification into the target cells (peripheral blood mononuclear cells, PBMCs), in a cohort of 24 pediatric liver recipients after a median follow-up of 5.23 years. Moreover, we analyzed the influence of ABCB1 (3435C>T and 1199A>G), CYP3A*3 and CYP3A4*22 polymorphisms on the intralymphocyte distribution of tacrolimus. Methods: PBMCs were collected using CPT tubes; cells count and the mean cellular volume were evaluated with a coulter counter. Tacrolimus concentration was quantified, after cell lyses, using ultra performance liquid chromatographywith tandemmass inpositive ionmode, coupledwith thenewautomatedon-line solid phase extraction technology. Results: A median value of 49.5ng/mL (range 14.4–358.9) of tacrolimus PBMCs concentration was found, corresponding to a 12.7-fold wider range than the whole blood levels simultaneously analyzed. Although a significant correlation with mean tacrolimus blood levels could be observed, tacrolimus intracellular accumulation tended to be higher in ABCB1 G/A, although not statistically significantly, and in CYP3A5*3/*3 recipients. Conclusions:Although tacrolimus PBMCs concentration cannot be considered as a routine test yet, this method could bemore predictive of efficacy and toxicity of immunosuppressive therapy than whole blood levels. Further studies are required to evaluate the relationship with clinical outcomes. http://dx.doi.org/10.1016/j.dld.2014.07.025 LIVING DONOR LIVER TRANSPLANT (LDLT): THE PATIENT PERSPECTIVE Andrea Pietrobattista1,∗, Manila Candusso1, Maria Sole Basso1, Chiara Grimaldi2, Fabrizio Di Francesco2, Lidia Monti3, Jean De Ville De Goyet2, Giuliano Torre1 1 USC Epatogastroenterologia e Nutrizione, Ospedale Pediatrico Bambino Gesu, Roma, Italy 2 USC Chirurgia epato-biliare, Ospedale Pediatrico Bambino Gesu, Roma, Italy 3 USC Radiologia, Ospedale Pediatrico Bambino Gesu, Roma, Italy Objective: To evaluate the outcome of living liver donor transplantation in children. Methods: Retrospective analysis. Results: We performed 23 LDLTs out of 105 transplants in the past 5 years inRome, and thenumberhas been increasing; themain indication is cirrhosis in biliary atresia (20 cases, 87%) but it has been performed also in metabolic diseases such as primary oxalosis, MSUD and propionic academia. No recipient died, themean age at transplantwas 29.3months (SD 28.6, r. 6–132), themeanweight 13kg (SD6.7, r. 5.5–30.3), after amean144daywaiting list time (SD 250, r. 0–1040); the mean PELD score was 20 (SD 12, r. 0–38). The mean ischemic time was 244min in LDLT vs 517.3min in cadaveric transplants. The mother was the donor in 13 children, in one a relative; no death. Surgical complications occurred in 8 children (34.7%), 2 out of these in one baby; the rate is similar in cadaveric recipients (33.7%), Rejectionwasdiagnosed in47.8%of cases, biliary stenosis in 2 cases, resolved by percutaneous biliary drainage (1) and by surgery (1); one child reported portal thrombosis, treated by Meso-Rex shunt. No living donor reported any complication. Conclusions: LDLT is an important tool in dealing childrenwith end-stage liver disease, mainly if cadaveric donors are lacking; it could be a safe choose even in metabolic disorders, with an heterozygote donor. http://dx.doi.org/10.1016/j.dld.2014.07.026

Excluded segmental duct bile leak is the rarest type of post-hepatectomy bile leak and presents unique diagnostic and management features. Classical management strategies invariably entail a significant loss of functioning hepatic parenchyma. The aim of this study is to report a new liver-sparing technique to handle excluded segmental duct bile leakage. Two cases of excluded segmental duct bile leak occurring after major hepatic resection were managed by a Roux-en-Y hepatico-jejunostomy on the excluded segmental duct, avoiding the sacrifice of the liver parenchyma origin of the fistula. In both cases, classical management strategies would have led to the functional loss of roughly 50 % of the liver remnant. Diagnostic and management implications are thoroughly discussed. Both cases had an uneventful postoperative course. The timing of repair was associated with a different outcome: the patient who underwent surgical repair in the acute phase developed no long-term complications, whereas the patient who underwent delayed repair developed a late stenosis requiring percutaneous dilatation. Roux-en-Y hepatico-jejunostomy on the excluded bile duct is a valuable technique in selected cases of excluded segmental duct bile leakage.

Objective: The aim of the present study was to investigate the effects of basic fibroblast growth factor (bFGF) on the angiogenic properties of extracellular vesicles (EVs) secreted by adipose-derived mesenchymal stem cells (ASCs) in culture. Methods: We isolated EVs from ASC (ASC-EVs) cultured with bFGF (FGF-EVs) or without bFGF (b-EVs). We compared the EV angiogenic action on human microvascular endothelial cells (HMEC) in vitro by capillarylike structure formation assay and in vivo by subcutaneous injection of HMEC-containing Matrigel in SCID mice. We analysed micro-RNA composition of EVs by PCR array and we selected two mi-RNAs changed after bFGF stimulation: miR-223 and miR-21. We transfected HMEC with short antisense anti-miR-223 or with mimic miR- 21 to compensate the action of EVs. Results: In vitro, the total length and the number of branches of vessel-like structures formed by FGF-EVstimulated HMEC were significantly reduced in respect to b-EV stimulation and the structures were significantly larger than after b-EV stimulation. In vivo, vessels formed by FGF-EV-stimulated HMEC were significantly lower in number in respect to those formed by b-EV-stimulated HMEC, but they were significantly larger in size and contained cells positive for mouse smooth muscle actin. We found that bFGF led to molecular changes in ASCEVs characterized by decreased expression of angiogenic factors. Moreover, bFGF stimulation up-regulated the expression of the anti-angiogenic miR-223 and decreased the level of pro-angiogenic miR-21. The effects of FGFEVs were antagonized by the inhibition of miR-233 and by the miR-21 mimic Conclusions: The results indicate that culture conditions may modify the pro-angiogenic activity of ASCderived EVs, changing their protein and RNA contents. In particular, bFGF induces production of EVs that stimulate vessel stabilization rather than an increase in vessel number.

The cross-talk between beta cells and endothelium plays a key role in islet physiopathology and in the revascularization process after islet transplantation. However, the molecular mechanisms involved in this cross-talk are not fully elucidated. Extracellular vesicles (EVs) are secreted membrane nanoparticles involved in inter-cellular communication through the transfer of proteins and nucleic acids. The aims of this study were: 1) isolation and characterization of EVs from human islets; 2) evaluation of the pro-angiogenic effect of islet-derived EVs on human islet endothelial cells (IECs). EVs were isolated by ultracentrifugation from conditioned medium of human islets and characterized by nanotrack analysis (Nanosight), FACS, western blot, bioanalyzer, mRNA/microRNA RT-PCR array. On IECs, we evaluated EV-induced insulin mRNA transfer, proliferation, resistance to apoptosis, in vitro angiogenesis, migration, gene and protein profiling. EVs sized 236±54 nm, expressed different surface molecules and islet-specific proteins (insulin, C-peptide, GLP1R) and carried several mRNAs (VEGFa, eNOS) and microRNAs (miR-27b, miR-126, miR-130 and miR-296) involved in beta cell function, insulin secretion and angiogenesis. Purified EVs were internalized into IECs inducing insulin mRNA expression, protection from apoptosis and enhancement of angiogenesis. Human islets release biologically active EVs able to shuttle specific mRNAs and microRNAs (miRNAs) into target endothelial cells. These results suggest a putative role for islet-derived EVs in beta cell-endothelium cross-talk and in the neoangiogenesis process which is critical for engraftment of transplanted islets. © 2014 Figliolini et al.

OBJECTIVES: The specific contribution of the herniation of an abdominal antireflux fundoplication into the chest to symptomatic and therefore surgical failure remains unclear. METHODS: The study was conducted in 189 consecutive fundoplication patients, categorized as patients reoperated on for chest herniation of either an abdominal 360° (Group 1; n = 95) or a partial (Group 2; n = 10) fundoplication, and patients having undergone an intrathoracic 360° fundoplication for short oesophagus (Group 3; n = 84; reference group). There were four subgroups in Group 1: 1A: wrap still complete and perioesophageal; 1B: wrap still complete but perigastric; 1C: wrap still perioesophageal but partially disrupted and 1D: wrap perigastric and partially disrupted. RESULTS: The prevalence of defective symptoms (heartburn and regurgitation) was significantly lower (P < 0.0001) in Group 3 (0.0%) and Subgroup 1A (3.7%) than in Subgroups 1B (84.4%), 1C (86.7%) and 1D (100%) and Group 2 (100%). The prevalence of obstructive symptoms (dysphagia, chest pain, necrosis and perforation) was significantly higher (P < 0.0001) in Subgroup 1A (100%) than in Subgroups 1B (57.8%), 1C (60.0%) and 1D (25.0%). The prevalence of a short oesophagus, an abdominal wall hernia repair and high abdominal pressure episodes in reoperated patients were 13.7, 36.2 and 67.2%, respectively. CONCLUSIONS: Unlike perigastric or partial fundoplication, a 360° perioesophageal abdominal fundoplication, when herniated into the chest, is still effective against reflux. Obstructive symptoms are due to either diaphragmatic strangulation or perigastric migration of the wrap (slipknot effect). Short oesophagus, weakness of the abdominal wall and high abdominal pressure episodes favour the herniation process.

Hereditary factors play a fundamental role in the pathogenesis of breast cancer (BC). Approximately 15-20% of all BCs have been reported to show familial clustering. In spite of the recent demonstration and chromosomal localization of BC predisposing genes, clinical clues and careful inspection of pedigree still remain major instruments in HBC diagnosis. The aim of the present study was to develop minimum operational criteria for the selection of family groups at high risk of developing BC. Following a stepwise procedure, families were stratified into four clusters with increasing probability of genetic involvement. So far, 317 BC-prone families have been identified and distributed in the four groups, and 151 high risk women underwent our clinical and mammographic surveillance program. Among these, after a mean follow-up of 24 months, six BCs and one OC were diagnosed (one BC and one OC occurred in the same woman) and one 'interval' BC was observed. Since the prevalence rate so far detected is dramatically higher than that seen at the first round of Italian population-screening programs, our preliminary data support the usefulness of the proposed procedure in selecting high risk individuals.

OBJECTIVE: To determine whether early postoperative administration of erythromycin accelerates the spontaneous motor recovery process after elevation of the denervated whole stomach up to the neck. SUMMARY BACKGROUND DATA: Spontaneous motor recovery after gastric denervation is a slow process that progressively takes place over years. METHODS: Erythromycin was administered as follows: continuous intravenous (i.v.) perfusion until postoperative day 10 in ten whole stomach (WS) patients at a dose of either 1 g (n = 5) or 2 g (n = 5) per day; oral intake at a dose of 1 g/day during 1.5 to 8 months after surgery in 11 WS patients, followed in 7 of them by discontinuation of the drug during 2 to 4 weeks. Gastric motility was assessed with intraluminal perfused catheters in these 21 patients, in 23 WS patients not receiving erythromycin, and in 11 healthy volunteers. A motility index was established by dividing the sum of the areas under the curves of >9 mmHg contractions by the time of recording. RESULTS: The motility index after IV or oral administration of erythromycin at and after surgery was significantly higher than that without erythromycin (i.v., 1 g: p = 0.0090; i.v., 2 g: p = 0.0090; oral, 1 g: p = 0.0017). It was similar to that in healthy volunteers (i.v., 1 g: p = 0.2818; oral, 1 g: p = 0.7179) and to that in WS patients with >3 years of follow-up who never received erythromycin (i.v., 1 g: p = 0.2206; oral, 1 g: p = 0.8326). The motility index after discontinuation of the drug was similar or superior to that recorded under medication in four patients who did not experience any modification of their alimentary comfort, whereas it dropped dramatically parallel to deterioration of the alimentary comfort in three patients. CONCLUSIONS: Early postoperative contractility of the denervated whole stomach pulled up to the neck under either i.v. or oral erythromycin is similar to that recovered spontaneously beyond 3 years of follow-up. In some patients, this booster effect persists after discontinuation of the drug.

Background Esophagectomy with extensive lymph node dissection is the best way to give Barrett's patients with locally advanced adenocarcinoma a good chance of cure. Material and Methods Fifty-five patients underwent subtotal (n = 47) or distal (n = 8) esophagectomy for Barrett's adenocarcinoma (n = 43) or high-grade dysplasia (HGD) (n = 12). Thirteen patients (23.6%) never had had any reflux symptom before disclosure of the neoplastic lesion, and 20 patients (36.4%) had esophageal shortening. Ro resections (n = 50) included removal of the esophageal tube en bloc with the locoregional lymph nodes. Results An invasive carcinoma was found in the resected specimen of 4 of the 12 patients operated on for HGD. Two of the 5 patients whose metaplasia was surveyed endoscopically were operated on for an advanced lesion (T2N1, T3N1) because they had not strictly complied with the proposed schedule. One of the 4 patients whose HGD was followed up endoscopically until disclosure of deeper mucosal invasion had positive lymph nodes at operation. The prevalence of early lesions (Tis, T1, T2, No) was 7.4% in patients with tumor-related symptoms versus 85.7% in those having unrelated symptoms ( P = 0.0000), which resulted in a 5-year survival rate of 33.8% and 82.4%, respectively ( P = 0.0012). Five-year survival rate after Ro resection made for invasive carcinoma was 59.3% (all cases), 73.1% (No), 61.5% (≤5 positive lymph nodes), and 0% (>5 positive lymph nodes). Conclusions High-grade dysplasia is an indication for esophageal resection. Early detection of the neoplastic transformation of Barrett's metaplasia prior to the onset of obstructive symptoms gives the best chance of cure. Esophagectomy with radical lymph node clearance is capable of curing a large proportion of the patients having no or a limited number of metastatic lymph nodes.

This prospective study was carried on 20 patients (10 with liver cirrhosis and 10 with myelo-lymphoproliferative disorders), consecutively admitted to our ward for splenomegaly and thrombocytopenia, with the aim of evaluating the ability of Duplex-Doppler ultrasonography (DDUS) to discriminate between congestive splenomegaly and enlarged spleen caused by haematological disorders.Comparing the clinical/laboratory and DDUS findings for the two groups, it emerged that maximum-portal flow velocity (PFV) values revealed the most statistically significant differences: 17.31 SD 2.48 vs. 28.27 SD 3.53 (cm/s, P0.001). Discriminant analysis showed that max-PFV is the variable which by itself maximizes the separation between the two groups (F = 71.56; P0.0001). The patients with congestive splenomegaly exhibited lower max-PFV than the controls (17.31 SD 2.48 vs. 26.29 SD 2.38 cm/s, P0.001), unlike those with haematological diseases, whose max-PFV values were greater, albeit not significantly so (28.27 SD 3.53 vs. 26.29 SD 2.38 cm/s, P = 0.161).DDUS assessment of portal haemodynamics thus proved useful in the differential diagnosis of splenomegaly in asymptomatic patients since it distinguishes rapidly and non-invasively between congestive and haemotological splenomegaly. A lower-than-normal max-PFV value indicates congestive splenomegaly; a highish value, on the other hand, suggests a splenomegaly of haematological origin.

We report the outcome of liver transplantation (LT) in the only surviving patient with lathosterolosis, a defect of cholesterol biosynthesis characterized by high lathosterol levels associated with progressive cholestasis, multiple congenital anomalies and mental retardation. From her diagnosis at age 2 she had shown autistic behavior, was unable to walk unaided and her sight was impaired by cataracts. By age 7 she developed end-stage liver disease. After a soul-searching discussion within the transplantation team, she was treated with LT as this represented her only lifesaving option. At 1-year follow-up, her lathosterol levels had returned to normal (0.61 mg/dL from 13.04 ± 2.65) and her nutrition improved. She began exploring her environment and walking by holding onto an adult's hand and then independently. Her brain magnetic resonance imaging (MRI) had shown a normal picture at age 1, whereas a volume reduction of white matter with ex vacuo ventricular dilatation and defective myelinization were observed before transplant. At 5-year follow-up, a complete biochemical recovery, an arrest of mental deterioration and a stable MRI picture were achieved, with a return to her every day life albeit with limitations. Timely liver transplant in defects of cholesterol biosynthesis might arrest the progression of neurological damage.

a b s t r a c t INTRODUCTION: Chronic biliary obstruction consequence of a bile duct injury may require liver transplan- tation (LT) in case of secondary biliary cirrhosis, intractable pruritus or reiterate episodes of cholangitis. "Mass-forming" sclerosing cholangitis leading to secondary portal vein thrombosis and pre-sinusoidal portal hypertension has not been reported so far. PRESENTATION OF CASE: We present the case of a patient who underwent laparoscopic cholecystectomy for Mirizzi syndrome. The persistent bile duct obstruction due to a residual gallstone fragment was treated by a prolonged biliary stenting. Following repeated bouts of cholangitis, a fibrous centrohepatic scar developed, conglobating and obstructing the main branches of the portal vein and of the biliary tree. The patient developed secondary portal vein thrombosis and portal hypertension. After an extensive diagnostic work-up, including surgical exploration to rule out malignancy, the case was successfully managed by liver transplantation. DISCUSSION: Mass-forming sclerosis of the bile duct and biliary bifurcation may develop as a conse- quence of chronic biliary obstruction and prolonged stenting. Secondary portal vein thrombosis and pre-sinusoidal portal hypertension represents an unusual complication, mimicking Klatskin tumor. CONCLUSION: A timely and proper management of post-cholecystectomy complications is of mainstay importance. Early referral to a specialized hepato-biliary center is strongly advised. © 2013 The Authors. Published by Elsevier Ltd on behalf of Surgical Associates Ltd.

Severe hepatic trauma is a rare indication for liver transplantation (LT). We report our single-center experience of LT for hepatic trauma. Four new cases are discussed in light of a literature review in order to depict the pathways leading from hepatic trauma to LT and to assess the outcomes of this practice. LT is generally indicated in case of uncontrollable hemorrhage, acute liver failure, or post-traumatic late sequelae. Hepatic vessels thrombosis, sepsis, major hepatic resections, and a late referral are factors associated with the progression toward irreversible liver failure. Considering all reported cases, early patient and graft survival reached 68% and 62%, respectively, but in the last decade both have improved to 84%. LT after severe hepatic trauma is a sustainable practice considering the current good outcomes and the ineluctable death of these patients without LT.

Liver transplantation is currently the only effective therapy for fulminant liver failure, but its use is limited by the scarcity of organs for transplantation, high costs, and lifelong immunosuppression. Here we investigated whether human liver stem cells (HLSCs) protect from death in a lethal model of fulminant liver failure induced by intraperitoneal injection of D-galactosamine and lipopolysaccharide in SCID mice. We show that injection of HLSCs and of HLSC-conditioned medium (CM) significantly attenuates mouse mortality in this model. Histopathological analysis of liver tissue showed reduction of liver apoptosis and enhancement of liver regeneration. By optical imaging we observed a preferential localization of labeled HLSCs within the liver. HLSCs were detected by immunohistochemistry in large liver vessels (at 24 hours) and in the liver parenchyma (after day 3). Fluorescence in situ hybridization analysis with the human pan-centromeric probe showed that positive cells were cytokeratin-negative at 24 hours. Coexpression of cytokeratin and human chromosome was observed at 7 and, to a lesser extent, at 21 days. HLSC-derived CM mimicked the effect of HLSCs in vivo. Composition analysis of the HLSC-CM revealed the presence of growth factors and cytokines with liver regenerative properties. In vitro experiments showed that HLSC-CM protected human hepatocytes from apoptosis and enhanced their proliferation. Conclusion: These data suggest that fulminant liver failure may potentially benefit from treatment with HLSCs or HLSC-CM. (HEPATOLOGY 2013)

Sorafenib and Mammalian Target of Rapamycin Inhibitors after Liver Transplantation: A Single-Center Experience and Review of the Literature Hepatocellular carcinoma (HCC) recurrence after liver transplantation (LT) is observed in 10-15% of the patients and generally has a dismal prognosis. Little is known about the safety and efficacy of a therapeutic regimen including sorafenib and mammalian target of rapamycin inhibitors (mTORi) in this setting. The medical charts of the recipients of a LT presenting HCC recurrence and treated with sorafenib either alone or in combination with mTORi were retrospectively reviewed.

Background. Liver transplantation (OLT) is the gold standard therapy for patients with cirrhosis complicated by hepatocellular carcinoma (HCC) within Milan Criteria (MC). We evaluated the impact of the etiology of the underlying liver disease on long-term outcomes of patients undergoing OLT for HCC within MC having a Model for End-stage Liver Disease (MELD) score < 15. Methods. From November 2002 to December 2009, we performed 203 primary OLTs from brain-dead donors in recipients with HCC and cirrhosis with biochemical MELD scores below 15. We excluded 31 patients outside MC on the explant pathology of the native liver. The remaining 172 were divided into 3 groups according to the etiology of the underlying cirrhosis: hepatitis C virus-positive (HCVþ; n ¼ 78; 45%), hepatitis B virus-positive (HBVþ; n ¼ 65; 38%) and other indications (n ¼ 29; 17%). The groups were compared for donor and recipient features, donor-recipient match, and transplant variables. The study endpoint was long-term patient survival. Results. The groups were similar, except for a greater prevalence of hepatitis B core antibody-positive grafts in the HBVþ group and less frequent HCC bridging procedures in the other indications group. After a median follow-up of 72 months, HCC recurrence was observed in 8 (4.7%) patients (6 HCVþ, 2 other indications), 5 of whom died. Overall 5-year patient survival of 82%, revealed significant differences among groups: 98.3% in HBVþ, 67.1% in HCVþ, and 85.8% in other indications (HBVþ vs other indications: P ¼ .01; HBVþ vs HCVþ: P ¼ .0001; HCVþ vs other indications: P ¼ NS). In the HCVþ group, recurrent HCV hepatitis was the most frequent cause of death. Upon multivariate analysis, HBV positivity in the recipient was an independent predictor of better patient survival (hazard ratio ¼ 0.10, 95% confidence interval 0.02e0.64, P ¼ .013). Conclusions. Etiology of the underlying cirrhosis significantly influenced the long-term survival after OLT of patients with HCC within MC and MELD < 15. It should be taken into account in estimation of survival benefit.

Background. The stomach can be used either in its entirety or as a greater curvature tube for esophageal replacement. Methods. The study compares the gastric tube (group A; n = 112) to the whole stomach whose lesser curvature is denuded (group B; n = 100) in terms of technical complication and alimentary comfort. The clinical results are substantiated by assessment of the eating performance of patients and control subjects at a test meal, measurement of the gastric dimensions before and after both tailoring procedures, and intraarterial staining of the gastric wall. Results. Major differences between the two groups are cervical anastomosis stenoses (22.3% versus 6% [A versus B]; p = 0.008), fistulas (7.9% versus 1%; p = 0.0209), number of meals and snacks per day (4.6 versus 4; p = 0.0275), sensation of early fullness at meals (52.4% versus 17.8%; p < 0.0001), ratings given to the long-term alimentary comfort (presymptomatic condition = 10 points) (7.6 versus 8.8 out of 10 on average; p < 0.0001), and calories consumed in 1 minute at a test meal (59% [p < 0.05] versus 77% of those consumed by control subjects). The volume of the stomach is reduced by a range of 21.4% to 47.2% after tubulization (group A) whereas it increases by a range of 4.9% to 17.4% after denudation of the lesser curve (group B). Intraarterial staining of the gastric wall reveals the poor vascularity of the upper-most segment of the greater curve. Conclusion. Slight increase of the gastric capacity and maintenance of the submucosal vascular network account for the better results achieved with the whole stomach.

In microalbuminuria there is an increased cardiovascular risk not fully explained by the excess of conventional risk factors. To investigate whether or not microalbuminuria is associated with haemostatic abnormalities in Type 2 diabetic patients, we measured the prothrombin fragment 1 + 2, a marker of thrombin generation, and the thrombin-antithrombin complex, a marker of thrombin neutralization. Plasma levels of prothrombin fragment 1 + 2 and thrombin-antithrombin complex were assayed in 17 microalbuminuric patients (albumin excretion rate, AER 20-200 micrograms min-1) and in 17 comparable normoalbuminuric (AER < 20 micrograms min-1) Type 2 diabetic patients. Plasma prothrombin fragment 1 + 2 was significantly higher in microalbuminuric than in normoalbuminuric patients (1.09 +/- 0.06 vs 0.86 +/- 0.04 nM, p = 0.003). Individual values of F1 + 2 were above the upper limit of the normal range in 8/17 microalbuminuric and in none of the normoalbuminuric Type 2 diabetic patients. Plasma thrombin-antithrombin complex values were not significantly different in the two groups and were not correlated with AER. These results suggest that microalbuminuria is associated with a prethrombotic state and a relatively defective thrombin neutralization. Coagulation abnormalities might be part of the cardiovascular risk in microalbuminuric patients.

Biliary cystadenoma is a rare benign cystic tumor of the liver. The mainstay of treatment is complete resection, either by enucleation or by formal hepatectomy, since incomplete removal entails not only constant recurrence but also the risk of malignant transformation to cystadenocarcinoma. A case of symptomatic centrohepatic biliary cystadenoma involving the main vasculobiliary structures of the liver is reported. After an unsuccessful attempt at resection resulting in an intrahepatic biliary injury, relief of jaundice and radical excision were achieved by total hepatectomy and liver transplantation. The patient is now alive and well 4 years after transplant, disease-free, with normal liver and renal function while receiving everolimus monotherapy. This is the first report of liver transplantation performed for the treatment of this tumor. With the case on the background, diagnostic aspects and available therapeutic strategies for biliary cystadenoma are reviewed and discussed.

Objective Magnetic resonance imaging of hepatocellular carcinomas (HCCs) was performed before and after transcatheter arterial chemoembolization (TACE). The changes of tumor signal intensity were compared to residual tumor or tumor recurrence in the follow-up period. Materials and Methods Fifteen cirrhotic patients with HCC were studied. All patients were examined with MRI both before and 3 months after TACE. Requirement for the study was that all lesions were detectable by MR before TACE. Results Magnetic resonance imaging detected 31 tumors. The changes of tumor signal intensity were compared to residual tumor or tumor recurrence in the follow-up period. On T1-weighted (T1W) images before TACE, 16 tumors were hyperintense, 11 were isointense, and 4 were hypointense; on T2W images, 26 tumors were hyperintense, 5 were isointense, and none were hypointense. On T1W images 3 months after TACE, 8 tumors were hyperintense, 18 were isointense, and 9 were hypointense; on T2W images, 11 were hyperintense, 11 were isointense, and 9 were hypointense. All the tumors that became hypointense on T2W images after TACE did not recur on follow-up. All lesions that were still hyperintense on T2W images after TACE showed residual tumor during the follow-up. Among 11 tumors that were isointense on T2W images after TACE, 7 were hyperintense on T2W images before TACE; 6 of these did not recur. Four tumors were isointense on T2W images before and after TACE; 2 of these showed residual tumor in the follow-up. On T2W images after TACE, 15 of 16 HCCs that decreased in signal intensity did not recur on follow-up. On T1W images no correlation was seen between the changes of the signal intensity of the lesion and tumor recurrence in the follow-up; however, 9 of 17 HCCs that did not recur after TACE showed decreased signal intensity. All the tumors (10 of 10) with decreased signal intensity on both T1W and T2W images after TACE did not show tumor recurrence on follow-up. Conclusion The results suggest that MRI is useful in the assessment of the therapeutic effect of TACE in HCC.

Background Long-term prophylaxis of hepatitis B virus (HBV) positive liver transplanted subjects with intravenous hepatitis B immunoglobulin (HBIG) is effective, however use of intramuscular HBIG could be as effective with fewer adverse events and lower cost. Aim We conducted a prospective, non-randomized, clinical study to assess the efficacy and safety of HBIG from Grifols, Igantibe ® , for the prophylaxis of HBV reactivation. Methods Eighteen adult patients submitted to liver transplantation for HBV-related disease more than 18 months earlier were treated with doses of 2000 I.U. intramuscular Igantibe ® every 14 days for 6 months. Results Mean trough serum HBsAb IgG titers from months 4 to 6 (primary efficacy variable) were protective (≥150 I.U./L) at each time point. Individual measurements were also protective throughout the study. HBV replication remained negative for all available subjects until study completion. Pharmacokinetic analysis showed a half-life of 27 days and extensive exposure to the study drug. Safety and tolerability of intramuscular Igantibe ® were good, with only one adverse event. Conclusion Standard-dose intramuscular Igantibe ® administration proved efficacious in post-liver transplantation prophylaxis by attaining protective levels for up to 6 months, was safe and well tolerated. Pharmacokinetic analysis revealed a long half-life and extensive exposure.

Association of type 1 diabetes and cytomegalovirus (CMV) is suspected and CMV infections have also been linked to increased risk of new onset post-transplantation diabetes. We monitored response to islet autoantigens, pancreatic endocrine function, and CMV infections in one type 1 diabetic patient receiving pancreas allograft. Time course analyses of levels of islet autoantibodies (Abs), IFN-gamma ELISPOT response, analysis of T cell function, levels of C peptide together with CMV pp65 antigenaemia and viraemia and graft biopsy histopathology were performed in comparison with a cohort of diabetic recipients. Evidence of autoimmune activation to GAD and IA2, modification of CD4(+) CD25hi T cells, loss of pancreatic function, concomitantly with multiple CMV infections and allograft rejection with peri-insulitis is provided. The parallel between metabolic outcome, initiation and progression of autoreactivity to islet autoantigens and early CMV infections after transplantation, suggests that persistent CMV infections may be relevant to the pathogenesis of type 1 diabetes.

Coronary artery disease is the first cause of mortality in industrialized countries notwithstanding the diagnostic and therapeutic progresses. Electron beam computed tomography and multislice computed tomography with calcium score software seem to have an important role in the early diagnosis of coronary artery disease. Coronary calcium is associated with a high probability of subclinical atherosclerosis. In particular the area of calcification has a positive correlation with the histologically analyzed area of the atheromatous burden plaque. The pathophysiological mechanism may be that the calcium adherent to the plaque makes unstable the plaque with possible rupture. Several studies have analyzed the predictive value of calcium score in various subgroups of patients (asymptomatic, with chest pain, with diabetes) and they have confirmed the presence of large calcific deposits in subjects with a high cardiovascular risk. The correlation of the other risk factors with calcium score is unclear and whether this is due to genetic predisposition requires further investigation.

The aim of the study was to evaluate safety and efficacy of IP in LT, particularly in marginal grafts. From 2007 to 2008, 75 LT donors were randomized to receive IP (IP+) or not (IP-). Considering the graft quality, we divided the main groups in two subgroups (marg+/marg-). IP was performed by 10-min inflow occlusion (Pringle maneuver utilizing a toruniquet). Donor variables considered were gender, age, AST/ALT, ischemia time and steatosis. Recipient variables were gender, age, indication to LT and MELD/CHILD/UNOS score. AST/ALT levels, INR, bilirubin, lactic acid, bile output on postoperative days 1, 3 and 7 were evaluated. Histological analysis was performed evaluating necrosis/steatosis, hepatocyte swelling, PMN infiltration and councilman bodies. Thirty patients received IP+ liver. No differences were seen between groups considering recipient and donor variables. Liver function and AST/ALT levels showed no significant differences between the main two groups. Marginal IP+ showed lower AST levels on day1 compared with untreated marginal livers (936.35 vs. 1268.23; p = 0.026). IP+ livers showed a significant reduction of moderate-severe hepatocyte swelling (33.3% vs. 65.9%; p = 0.043). IP+ patients had a significant reduction of positive early microbiological investigations (36.7% vs. 57.1%; p = 0.042). In our experience IP was safe also in marginal donors, showing a protective role against IRI.

Seventeen benign peripheral nerve sheath tumors were studied using MR. In all cases T2 relaxation time, signal intensity on T1-weighted images (lesion/muscle ratio), detectability of nerve of origin, nerve-lesion relationship, and presence of a capsule were assessed. Sixteen tumors showed marked hyperintensity on T2-weighted images with T2 relaxation times values greater than 95 ms. One schwannoma was almost isointense with fat (T2 60 ms). All lesions were isointense with muscle on T1-weighted images. In schwannomas the nerve was usually situated at the periphery of the lesion and only in one case was it obliterated by the mass. In neurofibromas the nerve was either visible in a central position within the mass (two cases) or no longer visible (five cases). A capsule could be detected in 70% of the schwannomas and in 30% of the neurofibromas. In patients with soft tissue masses, MR may contribute to recognition of nerve sheath tumors by showing the nerve of origin and typical signal hyperintensity on T2-weighted images. It can also be helpful in distinguishing between schwannomas and neurofibromas by the location of the nerve of origin and the presence of a capsule.

Bartonella henselae is the causative agent of cat-scratch disease and other disorders, including hepatosplenic granulomatosis. This infection has only rarely been reported after solid organ transplantation, where it can mimic the more common post-transplant lymphoproliferative disease. Here we present a case of asymptomatic B. henselae hepatic and lymph nodal granulomatosis in a pediatric patient who had received orthotopic liver transplant 2 months before; we hypothesize that the causative agent was transmitted from the donor. This infection developed early in the post-transplant period; the disease involved only the graft liver and the regional lymph nodes, and the patient did not have a cat or any history of contact, scratches, or bites by a cat. In our patient this infection resolved successfully with a combination of 2 associated antibiotics and reduction of immunosuppressive therapy.

We compared 3-Tesla (3-T) and 1.5-Tesla (1.5-T) cardiac magnetic resonance imaging (MRI) for the assessment of myocardial viability in nearly identical experimental conditions.Thirty-five patients (mean age 63+/-11; 94.2% men) submitted to primary coronary angioplasty underwent both 3-T and 1.5-T cardiac MRI, which was considered the gold standard. Comparison was performed on the basis of the same viability imaging protocol, which included resting cine-MR [balanced fast-field echo (B-FFE) sequence] followed by contrast-enhanced MR to evaluate perfusion and delayed enhancement (DE). We then performed functional index measurements and visual estimation of kinesis, perfusion and DE referring to a 5-point scale. Image quality was assessed on the basis of signal to noise ratio (SNR) and contrast to noise ratio (CNR).We found nonsignificant differences between the two scanners (P=NS) in measuring the functional and viability parameters. Myocardial SNR was significantly higher with 3-T MRI compared with 1.5-T MRI (61.3% gain). Even though a loss of CNR was recorded in B-FFE and in first-pass perfusion sequences (12.4% and 23.7%, respectively), on DE images, we quantified the increase of SNR and CNR of infarction of 387.8% and 330%, respectively.We found that 3-T MRI showed high concordance with 1.5-T MRI in the evaluation of functional and viability parameters and provided better evidence of damaged myocardium.

AIM To assess the value of multidetector computed tomography (MDCT) in the non-invasive evaluation of stents. METHODS We studied 88 patients (142 stents): 48 with 1.2-mm MDCT, 40 with 0.6-mm MDCT considering accuracy in assessing the vessel lumen, stent patency and intra-stent restenosis. Coronary angiography comprised the gold standard. RESULTS Occlusion was detected, respectively, in three of 72 versus four of 70 cases. Patency was assessed in all cases. In-stent restenosis was diagnosed in two of eight cases with thin-slice MDCT. CONCLUSIONS 0.6-mm MDCT allows a better visualization of stent lumen and in-stent restenosis versus 1.2-mm MDCT.

OBJECTIVE: To assess the long-term results of the duodenal switch operation made for pathologic transpyloric duodenogastric reflux (DGR). SUMMARY BACKGROUND DATA: DGR symptoms and lesions are poorly responsive to medical treatment. METHODS: A duodenal switch operation was made on 48 patients suffering from pathologic transpyloric DGR either unrelated (n = 28) or secondary (n = 20) to previous upper gastrointestinal (GI) surgery, including cholecystectomy or vagotomy. The diagnosis was based on the combination of several objective arguments: a long history of gastric symptoms (ie, nausea, epigastric pain, and/or bilious vomiting) poorly responsive to medical treatment (48 of 48), gastroesophageal reflux symptoms unresponsive to proton-pump inhibitors (PPI) (23 of 29), gastritis on upper GI endoscopy (37 of 48) and/or at histology (28 of 41), presence of a bilious gastric lake at >1 upper GI endoscopy (30 of 48), DGR at diisopropyl iminodiacetic acid (DISIDA) scintigraphy scanning (7 of 13), pathologic 24-hour intragastric bile monitoring with the Bilitec device (40 of 41), and absence of Helicobacter pylori antral infection (39 of 41). RESULTS: At follow-up (median, 81 months), gastric symptoms were nil, had improved, and remained unchanged in 29 (60.4%), 16 (33.3%), and 2(4.2%) patients, respectively, and 1 patient experienced symptomatic recurrence after a 92-month symptom-free period (2.1%). Among the 44 patients who had postoperative upper GI endoscopy, 42 (95.5%) had no gastritis whereas 5 (11.3%) had an ulcer at the duodenojejunostomy. Gastric exposure to bile at postoperative 24-hour intragastric Bilitec test in 36 patients was nil, within the normal range, and still slightly pathologic in 15 (41.7%), 19 (52.8%), and 2 (5.5%), respectively. CONCLUSIONS: The duodenal switch operation made on patients in whom diagnosis of pathologic transpyloric DGR is supported by several objective arguments provides most of them with symptomatic and endoscopic improvement parallel to abolishment or normalization of gastric exposure to bile. Postoperative PPI therapy during a 2-month period is to be recommended to prevent the development of an anastomotic ulcer.

new arguments for answering those questions. 3 First, given the dismal natural course of the disease in spite of rigorous medical management, we are persuaded that the organ transplant approach should be considered in all patients with neonatal-onset, cobalamin-unresponsive MMA. In our patients, timely liver transplantation allowed an excellent clinical course both perioperatively and in the long-term, consistent with the results by Niemi et al. Second, we are convinced that transplantation should be performed early, ideally within the first year of life, thereby avoiding repeated metabolic decompensations and the consequent neurologic deterioration. Third, we believe that isolated liver transplantationshould bethe preferred option,asit providesthe greatest mutase enzyme activity (5-fold greater than kidney transplantation), sufficient for preserving renal function and avoiding, or at least delaying, the need for kidney transplantation. In light of these independent reports, early liver transplantation currently appears to be the best therapeutic option in patients with severe MMA. Although not fully curative, this approach will ensure healthier clinical outcome with respect to traditional medical management.

P0063 SOFOSBUVIR PLUS RIBAVIRIN FOR THE TREATMENT OF SEVERE HCV RECURRENCE AFTER LIVER TRANSPLANTATION: PRELIMINARY DATA FROM A SINGLE-CENTRE EXPERIENCE S. Marco, S. Martini, S. Strona, D. Arese, D. Cocchis, S. Mirabella, G. Rizza, F. Tandoi, R. Romagnoli, A. Ottobrelli, M.R. Torrani Cerenzia, F. Balzola, M. Salizzoni, M. Rizzetto. Gastrohepatology Unit, Liver Transplant Centre, General Surgery, A.O.U. Citta della Salute e della Scienza di Torino, Torino, Italy E-mail: marco.sacco10@gmail.com

Our aim was to evaluate the reliability of visual quantification of infarct extent on delayed enhanced magnetic resonance images.Eighty patients with previous myocardial infarction underwent cine and contrast-enhanced cardiac magnetic resonance imaging. The gadolinium-enhanced images were evaluated using a segmental model with two different methods: a visual score on a 5-point scale (0 no hyperenhancement, 4 hyperenhancement76% of myocardial wall) and a quantitative analysis based on the manual tracing of infarct contours with automatic threshold analysis. Each segment was also assigned a wall-motion score ranging from 0 (normokinesia) to 4 (dyskinesia). Statistical evaluation was performed.Out of 1,280 segments, 322 (25.1%) showed wall-motion abnormalities with enhancement in 327 (25.5%) evaluated with visual score and in 414 (32.3%) quantitatively. Among segments with normal or mild hypokinesia, 89.2% had a delayed-enhancement scoreor=1, whereas 80.2% of akinetic or dyskinetic segments had a scoreor=3. Mean time required for the visual and quantitative approach was 7+/-3 and 18+/-9 min, respectively. There was strong agreement between the visual and quantitative method (k=0.92; p0.01).Visual analysis of delayed enhancement is a timesaving approach that is sufficient to assess the transmural extent of infarction. Moreover, it has high correlation with wall-motion abnormalities.

Infection transmission from donor to recipient is a dreadful complication in transplantation. Although bacteremia was previously detected in 5% of donors without negative impact on recipient outcome, the current expansion of graft pool requires consideration of the infectious risk associated with suboptimal donors. This study aims to evaluate the incidence and risk factors of infection in unselected cadaveric liver donors, the occurrence of microorganism transmission to recipient and its influence on patient survival. Results of microbiologic cultures obtained before harvesting in intensive care unit (ICU) and routinely at harvesting from 610 consecutive liver donors were retrospectively analyzed. Evidence for bacterial and fungal transmission to the recipient was searched for in each culture-positive donor. One or more cultures were positive in 293 donors (48%), while bacteremia was present in 128 (21%). Culture-positive and bacteremic donors were of significantly older age and had longer ICU stays. At multivariate analysis, an ICU stay of 3 or more days was the only significant predictor of donor infection. Although 1-year patient/graft survival rates were not influenced by donor culture positivity, pathogen transmission occurred in 11 cases with high recipient 1-year mortality (45%). In those 11 cases, median donor age was 74 years, significantly much older than that of the other culture-positive donors. In conclusion, donors with a prolonged ICU stay are at increased risk of infection, while older donor age is associated with pathogen transmission to the recipient. Adequate donor maintenance and careful microbiologic surveillance and treatment, especially of elderly donors, may limit transmission of donor infection.

Objective: The aim of this study was to compare the image quality and the diagnostic accuracy of endorectal coil 1.5 T MRI (erMRI) and phased-array coil 3 T MRI (3-T MRI) in the pretherapeutic staging of prostate cancer. Methods: Twenty-nine consecutive patients, with pathological proven prostate cancer, have been examined in the same week with both erMRI and 3-T MRI. Two radiologists independently evaluated the image quality focusing on the following points: cancer tissue conspicuity, capsular infiltration and tumor involvement of seminal vesicles, neuro-vascular bundles, and apex. The radiologists assigned to each one of the above findings an image-quality score ranging from 1 to 5 (with 1 meaning "not visible," 2 "poorly visible," 3 "fairly visible," 4 "well visible with some artifacts," and 5 "clearly visible without artifacts"). Afterwards a comparative evaluation of the mean score obtained respectively by erMRI and 3 T MRI was done. Twenty-two of these 29 patients underwent radical prostatectomy. Assuming as gold standard the pathological report from the resected specimen, we compared the diagnostic accuracy of 3TMRI and erMRI in differentiating between tumors confined within the prostate gland (stage < T2) and tumors extending through the prostatic capsule (stages T3 and T4). Results: erMRI's image quality was found to be statistically significantly better than 3 T MRI's in evaluating tumor conspicuity, capsular infiltration, and seminal vesicles involvement. On the other hand, considering apex and NVB involvement no statistically significant difference was found between the 2 techniques. On the diagnosis of intracapsular or extracapsular tumor spread 3 T MRI and erMRI showed a comparable performance of sensitivity (75% vs. 83%), specificity (90% vs. 90%), positive predictive value (90% vs. 90%), and negative predictive value (75% vs. 81%). Conclusions: During preoperative prostate cancer staging, 3 T MRI, despite a slightly worse image quality, can provide comparable diagnostic information to erMRI.