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In this review, the authors describe the management of patients with colorectal liver metastases in the era of effective chemotherapies and advanced interventional radiology. They give special attention to the surgical procedures that decrease the operative mortality and morbidity and produce clear margins. They discuss the best timing for chemotherapy, resection of the primary tumor, and resection of the liver metastases in an effort to improve long-term survival. The use of preoperative portal vein embolization, two-stage hepatectomy for bilobar synchronous liver metastases, and the liver-first strategy have allowed for treatment of patients with advanced disease with a curative intent, and to obtain 5-year overall survival of 30 to 60% despite poor prognostic factors and a cure (no recurrence at 10 years) in more than 20% of patients. These rates would have been unimaginable only two decades ago.

OBJECTIVE: The authors objective is to report their recent experience with split-liver transplantation, focusing on the results and the impact on organ shortage. SUMMARY BACKGROUND DATA: There is an insufficient number of organs for liver transplantation. Split-liver transplantation is a method to increase the number of grafts, but the procedure is slow to gain wide acceptance because of its complexity and the poor results reported in previous series. METHODS: During the year 1995, the authors split 20 of 83 transplantable livers allocated to the authors' center, generating 40 grafts: 23 were transplanted locally and 17 were given to partner centers. During the same period, the authors accepted four split-liver grafts proposed to them by other centers. Overall, 27 split-liver transplantations were done in the authors' unit, accounting for 30% of the 90 transplants performed in 1995. RESULTS: One-year patient and graft survival rates for split-liver transplantation were 79.4% and 78.5%, respectively. Arterial and biliary complications rates were 15% and 22%, respectively, with none leading to graft loss. Primary nonfunction occurred in one case (4%). By splitting 24 of 87 transplantable livers (4 of which were in partner units), a total of 111 transplantations were performed, increasing graft availability by 28%. CONCLUSIONS: Split-liver transplantation is achieving graft and patient survival rates similar to that of whole liver transplantation despite a higher incidence of complications, which could become less frequent as experience is gained with this procedure. A wider acceptance of split-liver transplantation could markedly increase the supply of liver grafts.

International audience; AIM: To analyze the impact of previous cyst-enterostomy of patients underwent congenital bile duct cysts (BDC) resection. METHODS: A multicenter European retrospective study between 1974 and 2011 were conducted by the French Surgical Association. Only Todani subtypes I and IVb were included. Diagnostic imaging studies and operative and pathology reports underwent central revision. Patients with and without a previous history of cystenterostomy (CE) were compared. RESULTS: Among 243 patients with Todani types I and IVb BDC, 16 had undergone previous CE (6.5%). Patients with a prior history of CE experienced a greater incidence of preoperative cholangitis (75% vs 22.9%, P < 0.0001), had more complicated presentations (75% vs 40.5%, P = 0.007), and were more likely to have synchronous biliary cancer (31.3% vs 6.2%, P = 0.004) than patients without a prior CE. Overall morbidity (75% vs 33.5%; P < 0.0008), severe complications (43.8% vs 11.9%; P = 0.0026) and reoperation rates (37.5% vs 8.8%; P = 0.0032) were also significantly greater in patients with previous CE, and their Mayo Risk Score, during a median follow-up of 37.5 mo (range: 4-372 mo) indicated significantly more patients with fair and poor results (46.1% vs 15.6%; P = 0.0136). CONCLUSION: This is the large series to show that previous CE is associated with poorer short-and long-term results after Todani types I and IVb BDC resection.

BACKGROUND:: Liver first reversed management (RM) for the treatment of patients with simultaneous colorectal liver metastases (CRLM) includes liver directed chemotherapy the resection of the CRLM and the subsequent resection of the primary cancer. Retrospective data have shown that up to 80 of patients can successfully undergo a complete RM whereas less than 30 of those undergoing classical management (CM) do so. This registry based study compared the 2 approaches. METHODS:: The study was based on the LiverMetSurvey (January 1 2000 to December 31 2010) and included patients with 2 or more metastases. All patients had irinotecan and/or oxaliplatin based chemotherapy before liver surgery. Patients undergoing simultaneous liver and colorectal surgery were excluded. RESULTS:: A total of 787 patients were included: 729 in the CM group and 58 in the RM group. Patients in the 2 groups had similar numbers of metastases (4.20 vs 4.80 for RM and CM P = 0.231) and Fong scores of 3 or more (79 vs 87 P = 0.164). Rectal cancer neoadjuvant rectal radiotherapy and the use of combined irinotecan/oxaliplatin chemotherapy were more frequent in the RM group (P < 0.001) whereas colorectal lymph node involvement was more frequent in the CM group (P < 0.001). Overall survival and disease free survival were similar in the RM and CM groups (48 vs 46 at 5 years P = 0.965 and 30 vs 26 P = 0.992). CONCLUSIONS:: Classical and reversed managements of metastatic liver disease in colorectal cancer are associated with similar survival when successfully completed.

La debâcle economique et ecologique a laquelle nous assistons decoule de la perte organisee du controle des instances politiques sur les grands choix collectifs. L’ideologie neoliberale qui domine en partie le monde politique est fondee sur la croyance, quasi religieuse, en la toute-puissance des marches ; elle marginalise la sphere democratique. Or, les consequences du defaut de regulation, local et global, sont d’ores et deja dramatiques : les inegalites explosent, les limites des ressource...

Approximately one fourth of patients transplanted for hepatitis C virus (HCV)-induced liver failure progress to cirrhosis within 5 years, potentially requiring retransplantation. Although the relisting decision can be difficult in these patients, a score could help in selection of candidates with the best potential outcomes.A total of 1422 HCV-positive patients having undergone a retransplantation were included in this registry-based study. A multivariate Cox regression was performed, and an Akaike procedure was applied to design a score predicting survival after retransplantation and to allow an internal validation. Retained variables were donor age (DnAge), serum creatinine (Creat), International Normalized Ratio (INR), and serum albumin (Alb) at the second transplantation, recipient age (RecAge) at the first transplantation, and the interval between both transplantations (Int).The score was designed as 0.23×DnAge+4.86×log Creat-2.45×log Int+2.69×INR+0.10×RecAge-3.27× Alb+40. The receiver operating characteristic area under curve was 0.643 at 3 years, and survivals were 71%, 56%, and 37% for scores30, 30 to 40, and40, respectively (log rank0.0001).Overall, the proposed score is specifically designed for HCV-positive patients, accurately predicts survival after a liver retransplantation, and is helpful in the selection of candidates with the best potential outcomes.

Background Cytokine administration is a potential therapy for acute liver failure by reducing inflammatory responses and favour hepatocyte regeneration. The aim of this study was to evaluate the role of interleukin-1 receptor antagonist (IL-1ra) during liver regeneration and to study the effect of a recombinant human IL-1ra on liver regeneration. Methods We performed 70%-hepatectomy in wild type (WT) mice, IL-1ra knock-out (KO) mice and in WT mice treated by anakinra. We analyzed liver regeneration at regular intervals by measuring the blood levels of cytokines, the hepatocyte proliferation by bromodeoxyuridin (BrdU) incorporation, proliferating cell nuclear antigen (PCNA) and Cyclin D1 expression. The effect of anakinra on hepatocyte proliferation was also tested in vitro using human hepatocytes. Results At 24h and at 48h after hepatectomy, IL-1ra KO mice had significantly higher levels of pro-inflammatory cytokines (IL-6, IL-1β and MCP-1) and a reduced and delayed hepatocyte proliferation measured by BrdU incorporation, PCNA and Cyclin D1 protein levels, when compared to WT mice. IGFBP-1 and C/EBPβ expression was significantly decreased in IL-1ra KO compared to WT mice. WT mice treated with anakinra showed significantly decreased levels of IL-6 and significantly higher hepatocyte proliferation at 24h compared to untreated WT mice. In vitro, primary human hepatocytes treated with anakinra showed significantly higher proliferation at 24h compared to hepatocytes without treatment. Conclusion IL1ra modulates the early phase of liver regeneration by decreasing the inflammatory stress and accelerating the entry of hepatocytes in proliferation. IL1ra might be a therapeutic target to improve hepatocyte proliferation.

Objective To develop a score predicting the morbidity of liver resections in a center with low mortality. Design, Setting, and Patients The study was based on a prospective database of all liver resections performed at the Geneva University Hospitals between January 1, 1991, and October 30, 2009 (a total of 726 elective liver resections in 689 patients). Perioperative complications and their severity were graded according to the original classification by Clavien et al. Variables independently associated with the occurrence of complications were identified using a linear regression analysis model. A score was computed with all independent variables in an assessment population including two-thirds of the liver resections and was further validated in a population including one-third of the liver resections. Results Overall mortality was 0.7% (5 of 726 liver resections). We recorded 375 different complications in 259 hepatic resections (36% of resections had ≥1 complication). In the assessment group, resection of 3 or more segments, an American Society of Anesthesiologists score of 3 or higher, and resection for a malignant neoplasm independently predicted the risk of complications. A score integrating these 3 factors significantly predicted the risk of postoperative complications. The score also correlated with the occurrence of major complications. Conclusion The score allows for identification of patients most susceptible to complications, in whom efforts against specific postoperative morbidities can be concentrated.

Background & Aims Liver transplantation is a recognized treatment for selected patients with hepatocellular carcinoma (HCC), but transplant criteria still need to be refined, especially in the case of more advanced or downstaged tumors. Methods The present study investigated alpha-fetoprotein (AFP) as a predictor of outcome in 6817 patients listed with a diagnosis of HCC in the Scientific Registry of Transplant Recipients. Results Local pre-transplant HCC treatment was used in 41% of patients on the waiting list. Patients with AFP levels>400ng/ml at the time of listing who were downstaged to AFP⩽400ng/ml had better intent-to-treat survival than patients failing to reduce AFP to⩽400 (81% vs. 48% at 3years, p ⩽0.001) and comparable survival to patients with stable AFP⩽400ng/ml (74%, p =0.14). Patients with AFP levels decreased⩽400ng/ml and patients with levels persistently⩽400ng/ml also had similar drop-out rates from the list (10% in both groups) and post-transplant survival rates (89% vs . 78% at 3years, p =0.11). Such an AFP downstaging was associated with good survivals whatever the level of the original AFP (even if originally>1000ng/ml). Only the last pre-transplant AFP independently predicted survival ( p ⩽0.001), unlike AFP at listing or AFP changes. Conclusions Overall, downstaging HCC patients with high AFP is feasible and leads to similar intent-to-treat and post-transplant survivals to those of patients with AFP persistently low. Only last AFP appears relevant for patient selection before transplantation and should be used in combination with morphological variables.

Background. Sunitinib (SU) is a multitargeted tyrosine kinase inhibitor with antitumor and antiangiogenic activity. The objective of this trial was to demonstrate antitumor activity of continuous SU treatment in patients with hepatocellular carcinoma (HCC). Patients and Methods. Key eligibility criteria included unresectable or metastatic HCC, no prior systemic anticancer treatment, measurable disease, and Child-Pugh class A or mild Child-Pugh class B liver dysfunction. Patients received 37.5 mg SU daily until progression or unacceptable toxicity. The primary endpoint was progression-free survival at 12 weeks (PFS12). Results. Forty-five patients were enrolled. The median age was 63 years; 89% had Child-Pugh class A disease and 47% had distant metastases. PFS12 was rated successful in 15 patients (33%; 95% confidence interval, 20%–47%). Over the whole trial period, one complete response and a 40% rate of stable disease as the best response were achieved. The median PFS duration, disease stabilization duration, time to progression, and overall survival time were 1.5, 2.9, 1.5, and 9.3 months, respectively. Grade 3 and 4 adverse events were infrequent. None of the 33 deaths were considered drug related. Conclusion. Continuous SU treatment with 37.5 mg daily is feasible and has moderate activity in patients with advanced HCC and mild to moderately impaired liver dysfunction. Under this trial design (>13 PFS12 successes), the therapy is considered promising. This is the first trial describing the clinical effects of continuous dosing of SU in HCC patients on a schedule that is used in an ongoing, randomized, phase III trial in comparison with the current treatment standard, sorafenib (ClinicalTrials.gov identifier, NCT00699374).

Purpose Multifocal panhepatic hepatoblastoma (HB) without extrahepatic disease is generally considered as an indication for total hepatectomy and liver transplantation. However, after initial chemotherapy, downstaging of the tumor sometimes allows complete macroscopic resection by partial hepatectomy. This procedure is no longer recommended because of the risk of persistent viable tumor cells in the hepatic remnant. We report our experience with conservative surgery in such cases. Method Between 2000 and 2005, 4 children were consecutively referred to our unit with multinodular pan-hepatic HBs (classification PRETEXT IV of the International Society of Pediatric Oncology Liver Tumor Study Group SIOPEL). Three of them had extrahepatic disease at diagnosis. All patients were treated according to SIOPEL 3 and 4 protocols. Results Extrahepatic metastases were still viable in 2 of 3 patients after initial chemotherapy. These patients eventually died of tumor recurrence. In the 2 patients without residual extrahepatic disease, liver tumors had regressed, and complete macroscopic excision of hepatic tumor remnants could be achieved by conservative surgery. These 2 children are alive and well and free of tumor 7 years after diagnosis. Conclusions Conservative surgery may be curative in some multinodular PRETEXT IV HB patients, with a good response to preoperative chemotherapy and complete excision of all macroscopic tumor remnants. However, because of the lack of reliable predictors of sterilization of the microscopic disease in the residual liver, with subsequent poor prognosis, total hepatectomy and liver transplantation remain currently recommended in patients with multinodular PRETEXT IV HB without extrahepatic disease, even though some of these children are probably overtreated.

Background Hepatitis B immune globulins (HBIG) in combination with nucleos(t)ide analogues (NA) are effectively used for the prevention of hepatitis B virus (HBV) recurrence after liver transplantation (LT). However, associated treatment costs for HBIG are exceedingly high. Methods Fresh frozen plasma obtained from blood donors with high anti-HBs levels (hyperimmune plasma, HIP) containing at least 4,500 IU anti-HBs was used as alternative treatment for HBV recurrence prophylaxis post-LT. Results Twenty-one HBV-related LT recipients received HIP starting at transplantation, followed by long-term combination treatment with NA. Mean follow-up time was 4.5 years (range 0.5-12.6) and each patient received on average 8.2 HIP per year (range 5.8-11.4). Anti-HBs terminal elimination kinetic after HIP administration was 20.6 days (range 13.8-30.9), which is comparable to values reported for commercial HBIG products. All 21 patients remained free of HBV recurrence during follow-up and no transfusion-transmitted infection or other serious complication was observed. Seven patients developed reversible mild transfusion reactions. The cost for one HIP unit was US$140; average yearly HBIG treatment cost was US$1,148 per patient, as compared to US$25,000-100,000 for treatment with commercial HBIG. Conclusion The results of this study suggest that the use of HIP may be a useful and economical approach for the prevention of HBV recurrence post-LT if used in combination with NA. Additional prospective controlled studies in larger populations are needed to confirm these results.

Background: In patients with synchronous colorectal liver metastases, an approach reversing the traditional therapeutic order – i.e. starting with chemotherapy first, doing the liver surgery second, and performing the colorectal surgery last – is theoretically appealing as it avoids the risk of metastatic progression during treatment of the primary tumor. The present series updates on a previously reported pilot experience. Patients and Methods: 35 patients with advanced synchronous colorectal metastases and nonobstructive colorectal tumors were treated with the reversed approach. Data were collected in a prospective database. Results: The median number of metastases was 6, the median size of the largest metastasis was 6 cm. Five patients could not complete the program (one death from sepsis during chemotherapy, 3 cases of progressive disease under treatment, and one case of vanishing liver metastases). The remaining 30 patients responded and underwent R0 liver resections with no major complications. One patient needed a Hartmann’s procedure for obstruction after a first-step hepatectomy, and 1 patient had a rectal anastomotic leak. Median survival was 44 months. Overall survival rates of the 30 patients who completed the program at 1, 2, 3, 4 and 5 years were 100, 89, 60, 44 and 31%. Conclusions: The reverse approach appeared feasible and safe, with operability and survival rates better than expected for patients with similar severity. Potential problems, in particular regrowth of vanishing metastases and primary tumors, chemotherapy-associated liver damage, and large bowel obstruction, can be minimized by careful multidisciplinary selection, planning and execution.

Background: Several staging systems for patients with hepatocellular carcinoma (HCC) have been proposed, but studies of their prognostic accuracy have yielded conflicting conclusions. Stratifying patients with early HCC is of particular interest because these patients may derive the greatest benefit from intervention, yet no studies have evaluated the comparative performances of staging systems in patients with early HCC. Methods: A retrospective cohort study was performed using data on 379 patients who underwent liver resection or liver transplantation for HCC at six major hepatobiliary centres in the USA and Europe. The staging systems evaluated were: the Okuda staging system, the International Hepato-Pancreato-Biliary Association (IHPBA) staging system, the Cancer of the Liver Italian Programme (CLIP) score, the Barcelona Clinic Liver Cancer (BCLC) staging system, the Japanese Integrated Staging (JIS) score and the American Joint Committee on Cancer/International Union Against Cancer (AJCC/UICC) staging system, 6th edition. A recently proposed early HCC prognostic score was also evaluated. The discriminative abilities of the staging systems were evaluated using Cox proportional hazards models and the bootstrap-corrected concordance index (c). Results: Overall survival of the cohort was 74% at 3 years and 52% at 5 years, with a median survival of 62 months. Most systems demonstrated poor discriminatory ability (P > 0.05 on Cox proportional hazards analysis, c approximate to 0.5). However, the AJCC/UICC system clearly stratified patients (P < 0.001, c = 0.59), albeit only into two groups. The early HCC prognostic score also clearly stratified patients (P < 0.001, c = 0.60) and identified three distinct prognostic groups. Discussion: The early HCC prognostic score is superior to the AJCC/UICC staging system (6th edition) for predicting the survival of patients with early HCC after liver resection or liver transplantation. Other major HCC staging systems perform poorly in patients with early HCC.

Acute primary Toxoplasma gondii infection is usually considered to be a contraindication for solid organ transplantation. Recent reports of acute T. gondii infection have highlighted the need to include T. gondii serology in the pretransplant screening of solid-organ transplant recipients. However such serology might be misleading. We describe the case of a 25-year-old woman who received a liver transplantation for life-threatening liver failure due to hepatitis B virus infection. The presence of high IgM titers against T. gondii, as detected by membrane immunoassay, immunofluorescence, and mu-capture ELISA tests, together with the absence of IgG antibodies in the immediate pretransplant serology screening suggested acute primary T. gondii infection at the time of transplantation. We initiated a preemptive therapy with intravenous clindamycin and cotrimoxazole. However, negative PCR and IgA capture assays, together with the absence of a sustained IgG response finally excluded the initial diagnosis of primary toxoplasmosis, leading to discontinuation of antitoxoplasmosis therapy. This case illustrates the problem that, in the context of fulminant hepatitis B, serologic markers for acute primary toxoplasmosis can be falsely positive. Confirmation by PCR and IgA antibody determinations is required to confirm this diagnosis.

Background Bilobar colorectal metastases are a therapeutic challenge and require a multidisciplinary approach. The aim of this study was to describe the clinical and histological outcomes of patients having neoadjuvant chemotherapy and two-step hepatectomy with right portal vein occlusion for advanced bilateral colorectal metastases. Methods A series of 23 consecutive patients treated with curative intent according to a standardized multidisciplinary management protocol was reviewed. Results Of 23 patients, 22 completed the programme. There was no mortality and no Clavien grade III morbidity. Median survival from the start of treatment was 45 months, and 1-, 3- and 5-year Kaplan–Meier estimates were 95, 73 and 27 per cent respectively. On histology at the first operation, ten patients had a dangerous halo of proliferating tumour cells infiltrating the surrounding liver parenchyma, of variable importance (six focal and four diffuse), regardless of the response to chemotherapy of the metastases. The dangerous halo increased in prevalence and importance (six focal and seven diffuse) between the first and second operation. Conclusion Neoadjuvant chemotherapy followed by two-step hepatectomy with right portal vein occlusion is feasible, safe and may be advantageous to the patient. The appearance of a dangerous halo around the liver metastases may require adaptation of the surgical technique to decrease the risk of local recurrence.

This report correlates the clinical and biological findings, liver hemodynamics and histological features of focal INL in an infant with BA cirrhosis. An eight month old boy with BA, with previous successful porto-enterostomy, was admitted with signs of cholangitis and ascites. He was treated with antibiotics and diuretics with subsequent clinical improvement. Eight days later, while being fed with hyper-osmolar milk, he became febrile again: ASAT/ALAT climbed (9000/2300 IU/L), liver function deteriorated. Infectious work-up was negative. Liver-ultrasound showed reversed portal flow and a negative arterial diastolic flow. The patient recovered within five days under supportive treatment. A similar event recurred five days later. INL was suspected and semi-urgent living-related liver transplantation was performed, with uneventful post-operative course. Histology of the explanted liver showed extensive foci of INL of different ages. This report illustrates how the association of reversed portal and arterial diastolic flows, with subsequent liver hypoperfusion, may repeatedly cause foci of INL in BA cirrhosis, and lead to rapid progression to liver failure. Because of precarious hepatic blood supply in such patients, close monitoring of portal and diastolic arterial flows is recommended.

OBJECTIVES: Brushing, the standard sampling method at endoscopic retrograde cholangiography (ERC), lacks sensitivity for cancer detection. We assessed a novel sampling method using a grasping basket. METHODS: Fifty-six patients with a suspected malignant biliary stricture were randomized to biliary sampling at ERC using a basket (basket group, N = 30) or a brush (brush group, N = 26), followed by the alternate device. When deemed necessary, strictures were dilated (using 6-mm balloons exclusively). The primary end point was sensitivity for cancer detection at cytopathological examination of the first sample collected in each patient; the cytopathologist was blinded to clinical details and sampling method. All analyses followed an intention-to-treat principle. RESULTS: All 56 patients had successful sampling with both techniques; 50 (89%) had a final diagnosis of malignant stricture. Sensitivity for cancer detection with the first sample collected in each patient was significantly higher in the basket compared to brush group (20/25 [80%]vs 12/25 [48%], respectively, P= 0.018, OR 4.33, 95% CI 1.24-15.21). Seventeen (34%) of the 50 sample pairs collected from malignant cases showed discordant cytopathological results: 15 patients had a positive basket and a negative brush result while two had the inverse association (P= 0.002, OR 7.5, 95% CI 1.65-47.44). Basketting more frequently yielded positive samples from malignant strictures in case of presampling balloon dilation (27/32 [84%]vs 10/18 [56%], respectively, P= 0.043, OR 4.32, 95% CI 1.14-16.37). Specificity was 100% (both methods). CONCLUSION: Biliary sampling at ERC using a dedicated basket provided a significantly higher sensitivity for cancer detection than brushing; presampling stricture dilation significantly increased sensitivity.

The review summarises the contributions of chemotherapy, interventional radiology and surgery to the improved survival observed in patients with colorectal liver metastases. The rationale in favour of modern neoadjuvant chemotherapy regimens, of pro-generative manoeuvres to increase the volume of the future remnant liver, and of resection techniques that preserve its function is discussed. For advanced synchronous colorectal metastases, the arguments in favour of a reversed approach with systemic chemotherapy, liver surgery and colon surgery in that order, as opposed to the traditional approach of colon surgery first, or to a simultaneous liver and large bowel resection, are presented.

Background: The purpose of the study was to characterize histological response to chemotherapy of hepatic colorectal metastases (HCRM), evaluate efficacy of different chemotherapies on histological response, and determine whether tumor regression grading (TRG) of HCRM predicts clinical outcome. Patients and methods: TRG was evaluated on 525 HCRM surgically resected from 181 patients, 112 pretreated with chemotherapy. Disease-free survival (DFS) and overall survival (OS) were correlated to TRG. Results: Tumor regression was characterized by fibrosis overgrowing on tumor cells, decreased necrosis, and tumor glands (if present) at the periphery of HCRM. With irinotecan/5-fluorouracil (5-FU), major (MjHR), partial (PHR), and no (NHR) histological tumor regression were observed in 17%, 13%, and 70% of patients, respectively. With oxaliplatin/5-FU, MjHR, PHR, and NHR were observed in 37%, 45%, and 18% of patients, respectively. Five patients, treated with oxaliplatin, had complete response in all their metastases. MjHR was associated with an improved 3-year DFS compared with PHR or NHR. MjHR and PHR were associated with an improved 5-year OS compared with NHR. Conclusion: Histological tumor regression of HCRM to chemotherapy corresponds to fibrosis overgrowth and not to increase of necrosis. TRG should be considered when evaluating efficacy of chemotherapy for HCRM. Histological tumor regression was most common among oxaliplatin-treated patients and associated with better clinical outcome

Tumor recurrence after resection of hepatocellular carcinoma (HCC) can occur early (2 years) as metastases or de novo tumors. Interferon (IFN) has the potential for chemoprevention against hepatitis C virus (HCV)-related cirrhosis. A predetermined group of 150 HCV RNA-positive patients undergoing resection of early- to intermediate-stage HCC was stratified into 80 HCV-pure (hepatitis B anticore antibody [anti-HBc]-negative) and 70 mixed HCV+hepatitis B virus (HBV) (anti-HBc-positive) groups, then randomized to IFN-alpha (3 million units 3 times every week for 48 weeks [n = 76]) versus control (n = 74). The primary end point was recurrence-free survival (RFS); secondary end points were disease-specific and overall survival. Intention-to-treat and subgroup analysis on adherent patients were conducted. Treatment effects on early/late recurrences were assessed using multiple Cox regression analysis. No patient experienced life-threatening adverse events. There were 28 adherent patients (37%). After 45 months of median follow-up, overall survival was 58.5%, and no significant difference in RFS was detectable between the two study arms (24.3% vs. 5.8%; P = .49). HCC recurred in 100 patients (48 IFN-treated, 52 controls), with a 50% reduction in late recurrence rate in the treatment arm. HCC multiplicity and vascular invasion were significantly related to recurrence (P = .01 and .0003). After viral status stratification, while no treatment effect was apparent in the mixed HCV+HBV population and on early recurrences (72 events), there was a significant benefit on late recurrences (28 events) in HCV-pure patients adherent to treatment (HR: 0.3; 95% CI: 0.09-0.9; P = .04). In conclusion, IFN does not affect overall prevention of HCC recurrence after resection, but it may reduce late recurrence in HCV-pure patients receiving effective treatment.

The local effectiveness and clinical usefulness of multipolar radiofrequency (RF) ablation of liver tumours was evaluated. Sixty-eight image-guided RF sessions were performed using a multipolar device with bipolar electrodes in 53 patients. There were 45 hepatocellular carcinomas (HCC) and 42 metastases with a diameter < or =3 cm (n = 55), 3.1-5 cm (n = 29) and >5 cm (n = 3); 26 nodules were within 5 mm from large vessels. Local effectiveness and complications were evaluated after RF procedures. Mean follow-up was 17 +/- 10 months. Recurrence and survival rates were analysed by the Kaplan-Meier method. The primary and secondary technical effectiveness rate was 82% and 95%, respectively. The major and minor complication rate was 2.9%, respectively. The local tumour progression at 1- and 2-years was 5% and 9% for HCC nodules and 17% and 31% for metastases, respectively; four of 26 nodules (15%) close to vessels showed local progression. The survival at 1 year and 2 years was 97% and 90% for HCC and 84% and 68% for metastases, respectively. Multipolar RF technique creates ablation zones of adequate size and tailored shape and is effective to treat most liver tumours, including those close to major hepatic vessels.

Renal dysfunction is common after liver transplantation (LT). The aim of our study was to assess the prevalence of renal dysfunction 5 yr after LT and to identify risk factors for the development of this complication.A total of 134 adult patients underwent LT from 1987 to 1998 and 74.6% of them were alive 5 yr after. Pre-LT, 1 and 5 yr post-LT renal function were calculated by Cockroft and modification of diet in renal disease (MDRD) formula. Since 1987 glomerular filtration rate (GFR) has been measured by radiolabeled tracers clearance (RTC). Risk factors for GFR50 mL/min were analyzed using a multivariate logistic regression model.Mean pre-LT GFR was 79 and 85 mL/min with Cockroft and MDRD respectively; 11% of the patients had a GFRor= 50 mL/min. 5 yr after LT, mean GFR was 63, 61 and 70 mL/min with MDRD, Cockroft and RTC respectively, GFR decreased by 26%, and 25% of the patients had a GFR50 mL/min. Independent risk factors associated with impaired renal function were: trough levels of cyclosporin A (CyA)or= 150 microg/L or tacrolimus (FK)or= 10 microg/L at 1 yr and CyAor= 100 microg/L or FKor= 8 microg/L at 5 yr.5 yr after LT, patients have lost 26% of their initial GFR and 25% of them have a GFR50 mL/min. This complication is predicted by high levels of calcineurin inhibitors (CNI). Therefore CNI levels should be reduced as low as possible and use of alternative drugs should be considered.

Liver-cell adenomas are benign lesions of the liver occurring predominantly in young women. Hepatocellular carcinomas in most of the cases arise in a cirrhotic liver during the fifth or sixth decade. We describe the case of a 40-year-old woman in whom work-up for epigastric pain revealed a peptic ulcer and a large hepatic mass. Tests for chronic liver diseases were negative. Imaging findings and biopsy specimens of the tumour were inconclusive. The tumour was surgically removed and a hepatocellular carcinoma arising within a liver-cell adenoma in a non-cirrhotic liver was found. Malignant transformation of liver-cell adenoma has only been reported in a few case reports. Mechanisms of transformation remain unclear. The imaging findings as well as histological features are presented in detail and the literature is discussed.

Background: : Disseminated aspergillosis is thought to occur as a result of vascular invasion from the lungs with subsequent bloodstream dissemination, and portals of entry other than sinuses and/or the respiratory tract remain speculative. Methods: : We report two cases of primary aspergillosis in the digestive tract and present a detailed review of eight of the 23 previously-published cases for which detailed data are available. Results and Conclusion: : These ten cases presented with symptoms suggestive of typhlitis, with further peritonitis requiring laparotomy and small bowel segmental resection. All cases were characterized by the absence of pulmonary disease at the time of histologically-confirmed gastrointestinal involvement with vascular invasion by branched Aspergillus hyphae. These cases suggest that the digestive tract may represent a portal of entry for Aspergillus species in immunocompromised patients

Background In many patients with advanced synchronous liver metastases from colorectal tumours, the metastases progress during treatment of the primary, precluding curative treatment. The authors have investigated a management strategy that involves high-impact chemotherapy first, resection of liver metastases second and finally removal of the primary tumour in patients with adverse prognostic factors. Methods Twenty consecutive patients with non-obstructive colonic (nine patients) or rectal (11 patients) cancer and advanced synchronous liver metastases were treated according to this strategy. Median age was 56 years. Patients received between two and six cycles of 5-fluorouracil, oxaliplatin and irinotecan-based chemotherapy. Data were collected prospectively. Results Overall survival rates at 1, 2, 3 and 4 years after the start of treatment were 85, 79, 71 and 56 per cent respectively, with a median survival of 46 months. Sixteen of the 20 patients had complete removal of liver metastases and colorectal tumours (resectability rate 80 per cent). Conclusion This new strategy produced resectability and survival rates better than those expected from the published data on patients with disease of similar severity. It allows initial control and downstaging of liver metastases, and delivery of preoperative radiotherapy for rectal cancer without the fear that liver metastases will meanwhile progress beyond the possibility of cure.

Hepatopulmonary syndrome (HPS) is a frequent pulmonary complication of patients with end-stage liver diseases. HPS is diagnosed by hypoxemia and pulmonary vascular dilatation and is an independent risk factor of mortality. Orthotopic liver transplantation (OLT) is the only factor that modifies the natural course of HPS. Once patients with HPS have been transplanted, their long-term survival rate is similar to transplanted patients without HPS. Consequently, HPS is an indication of OLT whatever the severity of hypoxemia. However, besides the favorable long-term survival of HPS patients with OLT, a high postoperative mortality (mostly within 6 months) has been suggested. The aim of our study was to analyze the incidence of HPS and postoperative outcome after OLT in 90 consecutive patients. All patients were prospectively included and had blood gas analysis to detect HPS. Patients with hypoxemia had contrast echocardiography to confirm HPS. Nine patients had HPS with a 50 50 mmHg in all HPS patients transplanted.

Simultaneous pancreas-kidney (SPK) transplantation has become the therapy of choice for type 1 diabetic patients with end-stage renal disease. The current analysis examined the impact of HLA matching on graft outcome following SPK transplantation. The study population was obtained from patients enrolled in the Euro-SPK 001 study. PATIENTS AND METHODS: The effect of HLA matching on graft function and survival was assessed in 180 SPK recipients in whom complete donor-recipient HLA data were available. A group of 45 patients with 0 to 3 HLA mismatches (MM) was compared to 135 patients with 4 to 6 MM. RESULTS: There were no differences in 3-year kidney, pancreas, or patient survival rates between the 0 to 3 and 4 to 6 MM groups. Biological parameters of kidney and pancreas graft function were similar in both groups. Significantly more patients with 0 to 3 MM (66%) were rejection free at 3 years than those with 4 to 6 MM (41%; P = .003). The relative risk of acute rejection was 2.6 times higher among patients with 4 to 6 MM than among those with 0 to 3 MM. In conclusion, there was no evidence that HLA matching was associated with improved kidney or pancreas survival. However, a higher rate of acute rejection was observed with poor HLA matches, which may impact long-term survival.

[26] Gondolesi GE, Roayie S, Munoz L, Kim-Schluger L, Schiano T, Fishbein TM, et al. Adult living donor liver transplantation for patients with hepatocellular carcinoma: extending UNOS priority criteria. Ann Surg 2004;239:142–149. [27] Gondolesi G, Munoz L, Matsumoto C, Fishbein T, Sheiner P, Emre S, et al. Hepatocellular carcinoma: a prime indication for living donor liver transplantation. J Gastointest Surg 2002;6:102–107. [28] Bruix J, Llovet J. Prognostic prediction and treatment strategy in hepatocellular carcinoma. Hepatology 2002;35:519–526. [29] Kulik L, Abecasis M. Living donor liver transplantation for hepatocellular carcinoma. Gastroenterology 2004;127:S277–S282. [30] Kulik L, Blei A, Axelrod D, Koffron A, Al-Saden P, Abecassis M. The effect of preadjuvant therapy on the recurrence rate of HCC in patients with a ‘fast-track’ liver transplant. AASLD Abstract 2004;150. [31] Lu DSK, Yu NC, Raman SS, Lassman C, Tong MJ, Britten C, et al. Percutaneous radiofrequency ablation of hepatocellular carcinoma as a bridge to liver transplantation. Submitted for publication. [32] Llovet JM, Bruix J. Systematic review of randomized trails for unresectable hepatocellular carcinoma: chemoembolization improves survival. Hepatology 2003;37:429–442. [33] Yao FY, Kinkhavwala M, LaBerge JM, Bass NM, Brown M, Kerlan R, et al. The impact of pre-operative loco-regional therapy on outcome after liver transplantation for hepatocellular carcinoma. Am J Transpl 2005;5:795–804. [34] Belghiti J, Cortes A, Abdalla EK, Regimbeau JM, Prakash K, Durand F, et al. Resection prior to liver transplantation for hepatocellular carcinoma. Ann Surg 2003;238:885–892.

Background/Aims The results of liver transplantation for Budd–Chiari syndrome (BCS) are poorly known and the role and timing of the procedure are still controversial. The aim of this study was to investigate the results of transplantation for BCS, focusing on overall outcome, on prognostic factors and on the impact of the underlying disease. Methods An enquiry on 248 patients representing 84% of the patients transplanted for BCS in the European Liver Transplantation Registry between 1988 and 1999. Results Of the 248 patients, 70.4% were female and 29.6% male. The mean age was 35.7 years. The overall actuarial survival was 76% at 1 year, 71% at 5 years and 68% at 10 years. 77% of deaths occurred in the first 3 months: 47% were due to infection and multiple organ failure, and 18% to graft failure or hepatic artery thrombosis. Late mortality (>1 year) occurred in nine patients, due to BCS recurrence in four of them. The only pre-transplant predictors of mortality on multivariate analysis (Cox) were impaired renal function and a history of a shunt. Conclusions Liver transplantation for BCS is an effective treatment, irrespective of the underlying cause, and should be considered before renal failure occurs.

BACKGROUND: The aim of this study was to evaluate the in vitro and in vivo function of hepatocytes after immortalization, cryopreservation, encapsulation, and xenotransplantation into mice with fulminant liver failure (FLF). METHODS: Rat and human hepatocytes were isolated by collagenase digestion. Human hepatocytes were immortalized using lentiviral vectors. Rat and immortalized human hepatocytes (IHH) were encapsulated in 400 microm of alginate-poly-L-lysine (PLL; Sigma, Buchs, Switzerland)-alginate membranes and cryopreserved using a computerized device. In vitro, encapsulated hepatocytes (cryopreserved or noncryopreserved) were cultured; albumin secretion was measured by enzyme-linked immunosorbent assay. Microencapsulated (cryopreserved or noncryopreserved) hepatocytes were transplanted intraperitoneally to mice with FLF: group 1 (n = 10) transplantation of empty capsules; group 2 (n = 12) transplantation of free primary rat hepatocytes; group 3 (n = 12) transplantation of cryopreserved encapsulated rat hepatocytes; group 4 (n = 10) transplantation of encapsulated rat hepatocytes; group 5 (n = 9) transplantation of cryopreserved encapsulated IHH; group 6 (n = 10) transplantation of encapsulated IHH. RESULTS: Compared with free primary hepatocytes, cryopreserved or noncryopreserved encapsulated rodent hepatocytes showed similar levels of continuous in vitro albumin secretion over 1 week. Cryopreserved or noncryopreserved encapsulated IHH showed minimal albumin secretion compared with free primary human hepatocytes. Fulminant liver failure, produced by a combination of acetaminophen and 30% hepatectomy, resulted in a 20% to 30% host survival. In groups 1 and 2, survival was unmodified, compared with untreated mice. For groups 3 and 4, transplantation of cryopreserved or noncryopreserved encapsulated rat hepatocytes significantly increased survival rates to 66% and 80%, respectively (P < .01). For groups 5 and 6, transplantation of cryopreserved or noncryopreserved encapsulated IHH improved host survival to 50% and 55%, respectively (P < .05). CONCLUSIONS: Primary rodent hepatocytes maintained synthetic functions after encapsulation and cryopreservation. Immortalized human hepatocytes showed minimal albumin secretion in the absence of encapsulation and cryopreservation, suggesting that hepatocytes lose some specific functions after immortalization. After induction of FLF in mice, intraperitoneal transplantation of encapsulated (primary or immortalized, cryopreserved or noncryopreserved) xenogeneic hepatocytes significantly improved survival. These results indicate that naive and genetically modified hepatocytes can be successfully encapsulated, stored by cryopreservation, and transplanted into xenogeneic recipients with FLF to sustain liver metabolic functions.

Microchimerism (MC) is defined by the persistence of 50%. However, cytotoxic T-lymphocyte reactivity (CTL) against HLA class I donor antigens could be demonstrated 1 year posttransplant in 2 patients with a high level of early MC. MC is a dynamic process, which is easily detectable

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

Aim Islet transplantation is gaining recognition as a therapeutic option for selected diabetic patients. The immunosuppressive regimen based on sirolimus/low-dose tacrolimus is considered a major breakthrough that allowed considerable improvement in graft survival. A high incidence of side effects associated with such a regimen has been reported in the literature, but this immunosuppressive protocol is generally considered safe or even protective to the kidney. Herein, we analyze the impact of the sirolimus/low-dose tacrolimus–based protocol on kidney function. Patients and Methods Five islet-after-kidney and 5 islet-transplant-alone patients were enrolled and followed up. Renal function was assessed by the periodic measurement of serum creatinine and by the presence of albuminuria. Metabolic control markers and graft function were followed, as well as immunosuppressive whole blood trough levels. Results Kidney function significantly decreased in 6 of 10 patients. Neither metabolic markers nor immunosuppressive drugs levels were significantly associated with the decreased kidney function. Conclusion Although a specific etiology was not identified, subsets of patients presented a higher risk for decrease of kidney function. The presence of low creatinine clearance, albuminuria, and long-established kidney graft were associated with poorer outcomes.

AIM: While hepatocellular adenomas (HAs) have often been studied as a unique entity, we aimed to better define current management of the various forms of HAs. METHODS: Twenty-five consecutive patients operated for solitary-uncomplicated (9), multiple (6), and ruptured (10) HAs were reviewed according to management strategies and outcomes. RESULTS: All solitary-uncomplicated HAs (ranged 2.2-14 cm in size) were removed. Out of 25 HAs, 2 (8%) included foci of carcinoma. In the multiple HA group, previously undiagnosed tumors were identified during surgery in 5/6 cases. In three cases with multiple spread HA, several lesions had to be left unresected. They remained unmodified after 4-, 6-, and 6-year radiological follow-up. Patients with ruptured HA (ranged 1.7-10 cm in size) were initially managed with hemodynamic support and angiography, allowing the embolization of actively bleeding tumors in two patients. All ruptured tumors were subsequently removed 5.5 d (range 4-70 d) after admission. CONCLUSION: Tumors suspected of HA, regardless of the size, should be resected, because of high chances of rupture causing bleeding, and/or containing malignant foci. Although it is desirable to remove all lesions of multiple HA, this may not be possible in some patients, for whom long-term radiological follow-up is advised. Ruptured HA can be managed by hemodynamic support and angiography, allowing scheduled surgery.

The aim of this study was to evaluate in vitro and in vivo functions of isolated hepatocytes after immortalization, cryopreservation, encapsulation and xenotransplantation into mice with fulminant liver failure (FLF).Rat and human hepatocytes were isolated from normal liver tissue by collagenase digestion. Human hepatocytes were immortalized using lentiviral vectors coding for SV 40 large T antigen, Bmi-1 and telomerase. Rat and immortalized human hepatocytes (IHH) were encapsulated in 400 micron alginate-PLL-alginate membranes and cryopreserved using a computerized device. In vitro, encapsulated hepatocytes (cryopreserved or freshly isolated) were cultured in albumin-free medium and albumin production was measured by enzyme-linked immunosorbent assay (ELISA). In vivo, a model of FLF was established in C57/BL6 mice by acetaminophen administration (700 mg/kg i.p.) followed 15 h later by a 30% hepatectomy. Microencapsulated (cryopreserved or freshly isolated) hepatocytes were transplanted intraperitoneally to mice with FLF and the following experimental groups were performed: group 1 (n = 10) Tx of empty capsules; group 2 (n = 12) Tx of free primary rat hepatocytes; group 3 (n = 12) Tx of cryopreserved encapsulated rat hepatocytes; group 4 (n = 10) Tx of fresh encapsulated rat hepatocytes; group 5 (n = 9) Tx of cryopreserved encapsulated IHH; group 6 (n = 10) Tx of fresh encapsulated IHH. Animals were killed at regular intervals and histopathology of microcapsules and liver tissue was obtained.In vitro, cryopreserved or fresh encapsulated rodent hepatocytes showed a progressively decreasing albumin secretion over 1 week in culture. In contrast, cryopreserved or fresh encapsulated IHH showed minimal, but stable albumin secretion. In vivo, FLF was achieved by combination of acetaminophen with 30% hepatectomy, resulting in a reproducible survival of 23% +/- 5%. In groups 1 and 2, survival rates were not improved significantly compared with untreated mice. In groups 3 and 4, Tx of cryopreserved or fresh encapsulated rat hepatocytes significantly increased survival rate to 66% and 80%, respectively (P0.01). In groups 5 and 6, Tx of cryopreserved or fresh encapsulated IHH improved survival to 50% and 55%, respectively (P0.05). Histopathology revealed that encapsulated hepatocytes were viable up to 2 weeks post-Tx.Primary rodent hepatocytes maintained synthetic functions after encapsulation and cryopreservation short-term. IHH showed minimal albumin secretion in the absence of encapsulation and cryopreservation, suggesting that hepatocytes loose specific functions after immortalization. After induction of FLF in mice, intraperitoneal Tx of encapsulated (primary or immortalized, fresh or cryopreserved) xenogeneic hepatocytes significantly improved survival. These results indicate that naïve and genetically modified hepatocytes can successfully be encapsulated, stored using cryopreservation, and be transplanted into xenogeneic recipients with liver failure and sustain liver metabolic functions.

This study compares ferucarbotran-enhanced magnetic resonance (MR) imaging with spiral computed tomography (CT) in the clinical management of patients with suspected hepatic malignancy. One hundred fifty-nine patients with suspected liver malignancy were included in a prospective, multicenter, phase IIIB clinical trial. Patients were examined with baseline plus contrast-enhanced spiral CT and with baseline plus ferucarbotran-enhanced MR imaging. For each patient, four maps of liver lesions were constructed by a trusted blind party on the basis of (a) baseline plus contrast-enhanced spiral CT, (b) baseline MR imaging, (c) baseline plus ferucarbotran-enhanced MR imaging, and (d) final diagnosis. Three blinded experts evaluated the treatment options for each map. The concordance of the treatment choice based on imaging with the treatment choice based on final diagnosis was verified. The final therapeutic decision was radical therapy for 85 patients, palliative therapy for 49 patients, and no treatment for 25 patients who had a final diagnosis of benign lesion. Proper treatment allocation was achieved in 121 (76%) of 159 patients when the evaluation was based on liver maps obtained from spiral CT, in 97 (61%) of 159 patients when the evaluation was based on liver maps obtained from baseline MR imaging, and in 136 (85%) of 159 patients when the evaluation was based on liver maps obtained from baseline plus ferucarbotran-enhanced MR imaging. MR imaging with ferucabotran was significantly superior to spiral CT for correct treatment allocation (P = 0.0167). Ferucarbotran-enhanced MR imaging is superior to spiral CT in clinical management of patients with suspected hepatic malignancy.

We have recently worked further on our database of patients with post-transplant hepatocellular carcinoma (HCC) recurrence and have realized that a systematic error was made in the analysis conducted for our original publication. The error was linked to the calculation of post-recurrence survival, which was shorter than originally stated. Instead of the published median survival of 18.8 ± 6.8 months, the true survival was of 6.3 ± 1.2 months (with a mean of 10.6 ± 3.0 months). As a result, the appropriate Fig. 1b is as follows

Objective. The objective of this article is to report a single-center experience with islet autotransplantation after extensive pancreatic resection for benign tumors of the pancreas. Materials and Methods. Seven patients underwent extensive left pancreatectomy for benign lesions located at the neck of the pancreas. Once an unequivocal diagnosis of a benign nature was ascertained, the rest of the specimen was processed and the unpurified pancreatic digest was infused into the portal vein. The results were compared with those of 8 autotransplantations performed for chronic pancreatites over the same period. Results. Tumors were 4 cystadenomas, 2 insulinomas and 1 neuroendocrine tumor. Mean islet yields were 275,000 islet equivalents (IEQ) versus 129,000 in chronic pancreatitis (P =.04) or 6700 IEQ/g of tissue versus 1900 (P =.002), resulting in transplantation of 4200 IEQ/kg body weight vs 2150 in chronic pancreatitis (P =.03), respectively at 4-month to 7.5-year follow-up, all patients are alive and 6 of 7 are off insulin. All patients off insulin after at least 1 year currently have a normal IVGTT, with K values ranging between -1.19 and -2.36 (normal < -1.00). All patients, including 1 on insulin, display positive basal and glucagon-stimulated C-peptide levels. Conclusions. Compared with chronic pancreatitis tissue resected for benign tumors is more likely to achieve good islet yields, and thus insulin independence after autotransplantation. Islet autotransplantation should be considered when extensive pancreatectomy is required for resection of a benign tumor, and only if the benign nature of the lesion is demonstrated unequivocally.

Liver transplantation is a standardized therapy for end-stage liver disease. With current immunosuppressive protocols and patient care, ten-year patient survival rate has reached 60%. Several medical complications may develop during this period, including renal dysfunction, hypertension, diabetes mellitus, hyperlipidemia, and metabolic bone disease. The aim of this article is to analyze long-term results of several clinical trials reporting common medical dysfunctions after liver transplantation and to discuss their management.

Living donor liver transplantation is a relatively new procedure in which the right side of the liver is harvested in a healthy donor and transplanted into a recipient. After the first case in 1994, over 3000 cases have been done worldwide. This review summarizes the reasons why the procedure is needed, describes its main technical aspects, highlights the boundaries in which it can be done safely, summarizes the current experience worldwide and describes the main points of the program in our unit. We argue that living-donor transplantation is a viable alternative to a long time on the waiting list for several patients, and it can be performed safely and successfully provided that all precautions are undertaken to minimize the risks in the donor and to increase the chances of a good outcome in the recipients. If these prerequisites are met, and within the framework of a structured multidisciplinary program, we believe that living-donor liver transplantation should be funded by health insurances as a recognized therapeutic option.

Insulinoma is a rare, almost always benign endocrine tumor of the pancreas, clinically characterized by hyperinsulinemic, hypoglycemic episodes. Surgical excision is the therapy of choice, which may lead to postpancreatectomy diabetes mellitus in the case of extensive pancreatic resection. We present the cases and the metabolic follow up of two patients, 81 and 73 years old, with insulinoma localized close to the main duct in the pancreatic neck. Both patients underwent an 80% left pancreatectomy, avoiding a pancreatico-enteric anastomosis. In order to prevent postpancreatectomy diabetes, the islets from the tumor-free part of the resected pancreas were isolated and injected via a right colic vein into the portal system. After a follow up of 6 and 3 years respectively, both patients remained insulin-independent without any dietary restrictions. Fasting and glucagon-stimulated C-peptide-levels and glycosylated hemoglobin remained within normal range. There were no signs of recurrent insulinoma. Liver biopsy performed in one patient at 1 year after autotransplantation, showed intact, insulin-producing islets within the portal spaces. In conclusion, autologous islet transplantation can preserve the insulin secretory reserve after extended left pancreatectomy for the treatment of benign tumors in the pancreatic neck.

During fetal development, the ductus venosus (ductus venosus Arantii) connects the umbilical portion of the left branch of the portal vein to the inferior vena cava, shunting oxygenated umbilical cord blood away from the liver. After birth the duct obliterates and persists as the ligamentum venosum or Arantius’ ligament. Because of its functional role, it is commonly believed that the ligament runs from the left branch of the portal vein to the vena cava itself. But attention to anatomical detail demonstrates that the fibers of the ligament insert either on the left hepatic vein or at the junction between the left hepatic and the middle hepatic veins (Figs. 1, 2). We describe a maneuver that takes advantage of the insertion of the ligamentum venosum to isolate and tape the left hepatic vein, or the common trunk of the middle and left hepatic veins. This maneuver is useful to pass a vessel loop to prepare for in situ left lobe splitting or for pediatric living donor liver transplantation. With further dissection, the maneuver can be used to encircle the common trunk of the left and middle hepatic veins to prepare for harvesting of the left liver for living donor or split liver transplantation or for selective hepatic vein occlusion during liver resections.