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Brain death secondary to cerebrovascular disease is a possible early complication of orthotopic liver transplantation. If liver graft continues to function normally, the reuse of liver for another patient may be considered. We report three cases of successful reuse of liver grafts after death of the first recipient. In our experience, liver graft can be reused in the first weeks after a previous transplantation provided that liver function is good, in the absence of systemic uncontrolled infection, graft rejection and after gross graft examination at laparotomy.

A randomized study was conducted of hilar dissection and the "glissonean" approach and stapling of the pedicle for major hepatectomies to contrast their feasibility, safety, amount of hemorrhage, postoperative complications, operative times, and costs.The "glissonean" approach is reported as requiring a shorter portal triad closure time; furthermore, the procedure seems to expedite the transection of the liver.Between 1998 and 2001, 80 patients were enrolled in this study. The major liver resections included 15 extended right, 7 extended left, 42 right, and 16 left hepatectomies. The patients were randomly assigned to the hilar dissection group (G1; n = 40) or to the "glissonean" approach and stapling of the portal triad group (G2; n = 40).The groups were equally matched for age, sex, diagnosis, mean resected specimen weight, number of tumoral lesions, type of liver resection performed, and percentage of patients with margin invasion (G1: 4; 10% vs G2: 5; 12.5%). The duration of the 2 procedures was similar (G1: 247 +/- 54 min vs G2: 236 +/- 43 min; P = 0.4). However, the duration of the hilar dissection was shorter for G2 (50 +/- 17 min) versus G1 (70 +/- 26 min; P0.001). By contrast, the duration of pedicular clamping was shorter for G1 (43 +/- 15 min) versus G2 (51 +/- 15 min; P = 0.015). No differences were observed in the amount of hemorrhage (G1: 887 +/- 510 mL vs G2: 937 +/- 636 mL; P = 0.7), and only 6 patients in G1 and 10 in G2 were transfused (P = 0.26). Morbidity rates were similar for both groups (G1: 23% vs G2: 33%; P = 0.3). Surgical injury of the contralateral biliary duct was not observed. However, 3 patients in G1 and 4 patients in G2 presented a biliary fistula that resolved spontaneously. Postoperative hospital stay was similar (G1: 8 [range, 6-24] vs G2: 9 [range, 5-31] days; P = 0.6). The postoperative levels of alanine transaminase (ALT) during the 2 first postoperative days were lower for G1 than G2. Cost of the surgical material was 1235.80 US dollars for G1 and 1301.10 US dollars for G2.The 2 techniques are equally effective procedures for treating hilar structures. Although en bloc stapling transection is faster, hilar dissection was associated with a shorter pedicular clamping time, less cytolysis, and the materials required were less expensive.

PRESERVATION injury (PI) is a major contributor to primary allograft failure after liver transplantation (LT). However, few studies have analyzed the predictive value of postreperfusion liver biopsies for the development of graft dysfunction and late complications. Extended cold preservation has been associated with biliary strictures. Consequently, it has been postulated that the ischemiareperfusion injury may play a role in the pathogenesis of some biliary complications. This study was performed to assess whether the presence of histologic lesions on postreperfusion (0Post) allograft biopsy is a predictive factor of postoperative biliary complications. Other secondary objectives were to examine the possible relationship between 0Post biopsy features and donor data, and to correlate postreperfusion histologic findings with graft and patient outcome.

HE SCARCITY OF donors and the increase in the number of transplant candidates have stimulated research to minimize the loss of donated organs. Preservation solutions are available to conserve the organs for a determinate period. In liver transplant (LT) Belzer and Brettschneider solutions give satisfactory results. However, graft malfunction remains a problem and other solutions are being examined. This randomized comparative study aims to examine the hepatic function of grafts perfused with Celsior solution (CS) and Belzer solution (BS) following liver transplant in adults.

THE SHORTAGE of donor livers for transplantation means that the use of liver grafts must be optimal. To ensure efficient use of the resources available, a precise definition of the causes of mortality (CMs) in these patients is essential. In the literature on the subject there are major discrepancies regarding the incidence of the CMs. This is so because the immediate cause (IC) of death is generally considered more important than other previous circumstances that contribute to the IC. We term the circumstances involved in the lead-up to death the principal cause (PC). It should also be stressed that the incidence of different CMs changes according to the follow-up time since transplantation. The objectives of the present study are first, to present a retrospective description of the global CMs in our patients and, second, to assess the distribution of mortality in different periods of the follow-up.

PRESERVATION INJURY is a major contributor to primary allograft dysfunction and failure after liver transplantation. Several studies have shown that cold ischemia (CI) can damage the sinusoidal liver cells. During this process many inflamatory mediators are released locally and to the blood stream. The damaged endothelial cells produce the activation and adhesion of leukocytes. Finally, the infiltration of polymorphonuclear cells increases the cold ischemic lesion. Platelet-activating factor (PAF) is an inflammatory mediator produced by many cell types. It has been implicated in the microcirculatory failure after cold and warm ischemia. PAF antagonist BN-52021 is a natural compound extracted from ginkgo-biloba tree. Its beneficial effect has been reported in ischemia reperfusion injury of many organs. The objective of our study was to demonstrate that the PAF antagonist BN-52021 can attenuate the preservation injury. The isolated perfused rat liver model was employed for reperfusion evaluation.

AFTER A previous study that analyzed early graft function, we conclude that donor age had a direct influence on the univariate analysis, but this did not happen on an independent basis. Following the conclusions of the above-mentioned study, donor’s age was not a contraindication for liver donation in our center. The aim of this study was to assess the impact of donor age on graft and patient survival.

4139 Background: NETs are a heterogeneous group of rare neoplasms. Preclinical studies have shown that IGFR overestimulation can lead to constitutional activation of mTOR pathway. The main objective of this study is to describe the activation status of IGF1R-mTOR pathway by immunohistochemistry in a series of NETs and to assess the association with IGF1R expression. Methods: We studied 69 paraffin tumour blocks: 28 pancreatic NETs (pNETs) (2 gastrinomas, 1 glucagonoma, 4 insulinomas and 21 non-functioning (nf) pNETs), 32 GI NETs (4 stomach, 8 colorectum, 18 ileum and 2 dudodenum) and 9 NETs from other origins (2 anterior mediastinum, 2 ovary, 3 bile duct and 2 kidney). The expression of IGF1R, phosphorylated (p) mTOR and (p)S6 has been determined by immunohistochemistry using anti-IGF1Rβ (sc-713), anti-Phospho-mTOR (S2448) (49F9, Cell Signaling) and anti-Phospho-S6 Ribosomal Protein (S235/336)(91B2, Cell Signaling). Results: Expression of IGF1R has been observed in 46 of 69 (66%) samples with the highest expression in 2/4 (50%) insulinomas, 5/21 nf pNETs (23%) and 3/18 ileum (17%). We have observed activation of the mTOR pathway by immunodetection of (p)mTOR in 14 of 69 samples (20%): 2/21 nf pNETs (9.5%), 1/8 colorectum (12.5%), 8/18 ileum (44%), 1/2 anterior mediastinum, 1/2 ovary, 1/3 biliar tract. We haven’t detected any (p)S6 activation in these samples. Consistent IGF1R-mTOR pathway activation was detected in 11/14 (78%) samples with mTOR positivity that also showed expression of IGF1R. The most relevant finding is that all of the 8 samples from ileum with activation of mTOR showed some degree of expression of IGF1R. Conclusions: 2/3 of NETs show varying levels of expression of IGF1R, but only 16% demonstrate activation of the IGF1R-mTOR pathway. While the positivity of (p)mTOR in pNETs is lower than expected, we have identified a subgroup of ileal NETs with consistent activation of both IGF1R and (p)mTOR which could help stratify patients in clinical trials involving modulation of this pathway. In contrast, none of the 69 samples studied was positive for (p)S6 which suggests this marker is not valid to be used in the clinic. Further validation studies are required to help clinical stratification for therapies against IGF1R mTOR pathways.

57 Background: It has been suggested that the sequential analysis of the mutational spectra at loci involved in the pathogenesis of tumors (mutational load distribution analysis [MLDA]) may reflect the biology of the tumor and/or the risk of cancer before the tumor emerges. Metrics derived from MLDA could assist quantifying risk, in early diagnosis, and in monitoring response to therapy. The aim of this study was to assess the efficacy of the NGS platform to obtain clinically relevant metrics derived from MLDA. Methods: Two sets of DNA samples were assessed: (i) 6 paired tumor/normal colorectal carcinomas and 8 colorectal adenomas; and (ii) 21 pancreatic carcinoma and 6 non-matched normal pancreas. Thirty amplicons from 6 genes (KRAS, BRAF, EGFR, CDKN2A, TP53, and PI3KCA) were sequenced using the Roche 454 GS FLX-TI platform. Data analysis was carried out by Variant Identification Pipeline (VIP) software and R (computing environment) commands. Total mutational load (TML) was calculated as the sum of all variants frequency for each sample. Results: In all, 18,626 variants were identified. Optimal filters applied to discard false positives were: (1) variants with an absolute frequency < 10x, (2) variants in homopolymer (HP) ≥ 6 nucleotides, (3) insertions and deletions (INDELs) in HP ≥ 5 nucleotides, and (4) INDELs in only one strand. Filtering yielded 870 variants from all samples remained as valid, 92 being unique. After discarding polymorphisms, variants classified as neutral by the Condel software and variants preferentially detected in normal tissues, 46 variants were used to compute TML. TML in colonic carcinomas and adenomas was higher than normal mucosa (0.83 vs. 0.607 vs. 0.128, p = 0.01). In pancreatic disease, TML for pancreatic carcinoma was higher than normal pancreas (0.716 vs. 0.135, p = 0.01). KRAS and TP53 analysis provide most of the information in both tumors, while PI3KCA adds information for colorectal carcinomas exclusively and CDKNA2 is informative in pancreatic samples. Conclusions: NGS provides a robust and quantitative measure of genetic alterations in tumor samples. MLDA is an effective tool for the classification of GI tumors.

Introduction The long term survival of patients with resectable pancreatic cancer (PC) is appalling, so data regarding what factors may influence outcome, following attempted curative resection is essential in order to optimize the treatment options for patients. Our aims were to analyze prognostic factors influencing survival in patients with resected PC in our institution. Methods Eligible participants included all persons diagnosed with pancreatic cancer from June 2004 to August 2008 that underwent pancreaticoduodenectomy for adenocarcinoma of only pancreatic head at the Surgical Department in Bellvitge Hospital. Risk factors associated with overall survival (OS) and Progression Free Survival (PFS) were assessed with the Kaplan-Meier survival method and the log-rank test. Demographic, tumour, and clinical variables were assessed using the Cox proportional hazards model. We also examined plasmatic VEGF (pVEGF) levels in these patients to evaluate the prognostic significance of these levels and correlate the results with the clinic- pathological features, microvascular density and K-RAS gene status. Results The median follow-up was 17.8 months for all patients. The median follow-up for living patients was 40 months (range 3-83 months). The median survival time for all patients was 21.26 months (95% confidence interval 13.29-29.24 months).The median Progression Free Survival for all patients was 15.76 months (95% confidence interval 4.99-26.54 months). Pathological stage was unfavorable prognostic factor in our pancreas cancer patients by univariate and multivariate analysis for OS and PFS. Perineural and vascular invasion as well as R1 resection were also negative prognostic factors for PFS. There was no survival correlation between high levels of p-VEGF and the remaining clinico-pathological features (including the number of resected nodes, microvascular density or K-RAS gene status). Conclusion Our results are consistent with the most important published studies and tumor characteristics remain the best significant features influencing survival after pancreatic cancer surgery.

THE SHORTAGE of organ donors and the increased demand for orthotopic liver transplantation (LTX) has led to new strategies to increase the availability of grafts for transplantation. In LTX because of familial amyloid polyneuropathy (FAP), the reuse of the liver for a patient aged more than 60 years was suggested by our group in 1993. The first was performed in Portugal and it is called domino liver transplantation (DLTX) or sequential LTX. We describe our experience in six cases of DLTX for FAP performed in our unit between February 1999 and September 2000.

The initial enthusiasm for orthotopic liver transplantation (OLT) in patients with hepatocellular carcinoma (HCC) soon vanished as early recurrences appeared [3, 5, 6]. OLT in HCC remains a controversial issue. We evaluated the efficacy of preoperative studies to select No-Mo patients and determined whether pT stage and histopathological grade (G) have a prognostic significance. A group of 25 patients, all previously thoroughly studied to rule out extrahepatic disease, underwent OLT for HCC. All patients were pNo after pathological study and none of the six patients who died in the postoperative period showed extrahepatic dissemination at necropsy (pMo). The recurrence rate was 43%. The 2 and 5 years actuarial survival was 62% and 43% respectively. The pT and G were not prognostic factors for long-term survival. We think that HCC is still a good indication for OLT because almost 50% of patients have good survival prospects.

Department of Surgery, Liver Transplant Unit, Hospital Universitari de Bellvitge, IDIBELL, 08907 Barcelona, Spain Department of Gastroenterology, Liver Transplant Unit, Hospital Universitari de Bellvitge, IDIBELL, 08907 Barcelona, Spain Department of Pathology, Liver Transplant Unit, Hospital Universitari de Bellvitge, IDIBELL, 08907 Barcelona, Spain Department of Surgery, Hospital U Lozano-Blesa, Zaragoza, Spain Department of Surgery, Hospital central de Asturias, Oviedo, Spain

Sir: We read with interest the article by J. P. Lerut et al. about liver transplantation (OLT) and portal vein anomalies [2]. This paper analyzes a very large (53 patients), but quite heterogeneous, group of patients. Preoperative portal vein thrombosis (PVT), phlebitis, and previous surgery for portal hypertension are difficult situations in OLT, and it is our opinion that the surgical management is not the same for all of them. With regard to PVT, it can be concluded from Lerut et al.’s study that blind or, more recently, eversion portal venous thrombectomy is the preferred surgical technique in 26 out of 32 cases (81 %). Mortality after this procedure was high (4/26; 15 %), and severe intraand postoperative bleeding were frequent complications (7/26; 27 %). Portal vein rethrombosis is another complication that has been frequently reported after this procedure [3,5]. Their experience with splenomesenteric confluence dissection is even worse, with 80 % mortality (4/5).

THE INTRODUCTION of new immunosupression therapies in the last two decades has led to great improvements in patient and graft survival after liver transplantation (OLT). Thus, the development of complications of chronic immunosuppressive therapy, such as atherosclerotic cardiovascular complications, have become a major concern. Some previous studies have suggested a reduced cardiovascular risk profile in patients with a tacrolimusbased treatment, but most studies are based on dual or monotherapies. The purpose of this study was to evaluate the safety and efficacy of a quadruple tacrolimus-based immunosuppression, mainly in relation to cardiovascular risk factors.

Sir: Among the vascular anomalies encountered during orthotopic liver transplantation (OLT), those involving the recipient's hepatic artery stand out because they are so difficult to solve. We describe the case of a 38-year-old male patient who underwent OLT due to posthepatitis liver cirrhosis. The patient was in Child's "B" stage with ascites and significant hemostasis impairment. The surgical technique used was the usual one, described by Starzl and Putnam [2]; arterial reconstruction was performed by anastomosis of the donor's celiac trunk to the recipient's common hepatic artery. The postoperative course was good and the patient was discharged 16 days later. The patient was readmitted 30 days after the OLT due to a cholangitis with dilatation and segmental stenosis of the intrahepatic bile ducts in the transhepatic cholangiography. Laboratory tests revealed cholestasis with increased bilirubin and alkaline phosphatase. An arteriography was performed that showed thrombosis of the common hepatic artery with the liver graft revascularizing from the superior mesenteric artery through the gastroduodenal artery. The patient's condition became progressively worse, with increased jaundice, weight loss, and denutrition. He underwent a second transplant operation 130 days after the first OLT with a diagnosis of sclerosing cholangitis secondary to hepatic ischemia, due to thrombosis of the hepatic artery. The cava preservation technique [4] was used in the operation. The vascular reconstructions were performed by end-to-end anastomosis from the donor's vena cava to the cuff of the recipient's suprahepatic veins, anastomosis of the portal vein following the usual technique, and an end-to-end anastomosis from the donor's common hepatic artery to the recipient's splenic artery, which had been previously cut and ligated at its distal end. The postoperative course was good except for positive viremia for CMV and leakage from the biliary anasto

Objectives: to highlight an infrequent occurrence using a series of clinical cases with symptoms and signs, and specific radiological findings allowing its diagnosis and treatment, which is in most cases successful. Patients and methods: a descriptive and retrospective study of patients diagnosed by computed tomography scanning and then treated with surgery in the Pancreas and Biliary Unit of a University Hospital from March 1999 to September 2005. Results: there were 6 female patients with a mean age of 33.5 years (range 11-72). Most common signs included pain and a palpable mass in the abdomen. Three patients were diagnosed by computed tomography scanning, and a differential diagnosis with a neuroendocrine tumor was performed for the remaining three subjects. Surgical treatment was adapted to each patient according to the findings and images seen in their computed tomography scans. Biopsy results confirmed the presumed diagnoses, and showed one case of solid pseudopapillary carcinoma of the pancreas. Average hospital stay was of 18.16 days (range 8-30). Mortality rate was 0%. No recurrences occurred during follow-up for 46.3 months on average (range 12-76). Conclusions: the presence of a huge mass in the pancreas of a young female should prompt suspicion for a solid pseudopapillary tumor. Given its low malignant potential, and the presence of specific radiographic patterns, its diagnosis should be accurate, as radical surgical treatment is effective.

The role of contaminated preservation fluid in the development of infection after liver transplantation has not been fully elucidated. To assess the incidence and etiology of contaminated preservation fluid and determine its impact on the subsequent development of infection after liver transplantation, we prospectively studied 50 consecutive liver transplants, and cultured the following samples in each instance: preservation fluid (immediately before and at the end of the back-table procedure, and just before implantation), blood, and bile from the donor, and ascitic fluid from the recipient. When any culture was positive, blood cultures were obtained and targeted antimicrobial therapy was started. We found that the incidence of contaminated preservation fluid was 92% (46 of 50 cases of liver transplantation per year), but only 28% (14/50) were contaminated by recognized pathogens. Blood and bile cultures from the donor were positive in 28% and 6% respectively, whereas ascitic fluid was positive in 22%. The most frequently isolated microorganisms were coagulase-negative staphylococci. In nine cases, the microorganisms isolated from the preservation fluid concurred with those grown from the donor blood cultures, and in one case, the isolate matched with the one obtained from bile culture. No liver transplant recipient developed an infection due to the transmission of an organism isolated from the preservation fluid. Our findings indicate that contamination of the preservation fluid is frequent in liver transplantation, and it is mainly caused by saprophytic skin flora. Transmission of infection is low, particularly among those recipients given targeted antimicrobial treatment for organisms isolated in the preservation fluid.