Targeting hepatocarcinogenesis model in C56BL6 mice with pan-aurora kinase inhibitor Danusertib.

Background: To elucidate the expression of Aurora kinases (AURK) and the anticancer effects of pan-aurora kinase inhibitor Danusertib in hepatocarcinogenesis model in C56Bl6 mice. Methods: Thirty mice C56Bl6 were randomly divided into Group A or control, Group B animals who underwent experimental hepatocarcinogenesis with diethylnitrosamine (DEN), and Group C animals with DEN-induced hepatocarcinogenenesis that treated with pan-aurora kinase inhibitor Danusertib. Primary antibodies for immunochistochemistry (IHC) included rabbit antibodies against Ki-67, DKK1, INCENP, cleaved caspase-3, NF-κB p65, c-Jun, ß-catenin. Hepatocyte growth factor receptor (C-MET/HGFR) and Bcl-2 antagonist of cell death (BAD) serum levels were determined using a quantitative sandwich enzyme immunoassay technique. Results: Inhibition of AURK reduced the number of DEN-induced liver tumours. Apoptosis and proliferation was very low in both DEN-induced and anti- AURK groups respectively. The hepatocellular adenoma cells of DEN-treated mice uniformly had ample nuclear INCENP whereas in anti- AURK markedly decreased. Expression of ß-catenin, NF-kB and c-Jun did not differ in liver tumors of both AURK -depleted and non-depleted mice. Conclusions: Depletion of AURK reduced the number of DEN-induced hepatic tumours. However, their size did not differ significantly between the groups.

Effects of Wnt-1 blockade in DEN-induced hepatocellular adenomas of mice.

Recent evidence has suggested that downregulation of the Wnt/ß-catenin signaling pathway may contribute to the development and growth of HCC. Consequently, elements of this pathway have begun to emerge as potential targets for improving outcomes of anti-HCC. Thus, the present study sought to examine the effects of Wnt-1 blockade using the classical diethylnitrosamine (DEN)-induced chemical carcinogenesis mouse model of HCC. The depletion of Wnt-1 using neutralizing antisera was done for ten consecutive days at the age of 9 months and mice were examined for the following 20 days. At that time, DEN-treated mice had multiple variably-sized hepatic cell adenomas. Anti-Wnt-1 was particularly potent in suppressing the expression of critical elements of the Wnt/ß-catenin signaling pathway, such as ß-catenin and Frizzled-1 receptor, however, not Dickkopf-related protein 1. This effect co-existed with the suppression of Cyclin D1, FOXM1, NF-κΒ and c-Jun commensurate with proliferation and apoptosis blockade in hepatocellular adenomas, and reduced Bcl-2 and c-Met in the serum of mice. Nonetheless, tumor size and multiplicity were found to be unaffected, suggesting that apoptosis may be equally important to proliferation in the context of counteracting DEN induced hepatocellular adenomas of mice.

The impact of expanded indications on short-term outcomes for resection of malignant tumours of the liver over a 30 year period.

BACKGROUND: There are two philosophical approaches to planning liver resection for malignancy: one strives towards zero postoperative mortality by stringent selection of candidates, thus inherently limiting patients selected; the other, accepts a low yet definite postoperative mortality rate, and offers surgery to all those with potential gain in survival. The aim of this study was to retrospectively analyse an alternative and evolving strategy, and its impact on short-term outcomes. METHOD: 3118 consecutive hepatectomies performed in 2627 patients over 3 decades (1980-2011) were analysed. Patient demographics, tumour characteristics, operative details, and postoperative outcomes were analysed. RESULTS: 1528 patients (58%) were male. Colorectal liver metastases (1221 patients, 47%) and hepatocellular carcinoma (584 patients, 22%) were the most common diagnoses. Anatomical resections were performed in 2045 (66%), some form of vascular clamping was used in 2385 (72%), and blood transfusion was required in 1130 (36%) patients. Use of preoperative techniques to increase feasibility and safety of complex liver resections allowed expansion of indications to include sicker patients with larger tumours in the later period of the study. Overall morbidity and mortality rates were 31% and 3% respectively. During the first vs. second half of the study period the postoperative morbidity and mortality were 19% vs. 36% (p < 0.001) and 2% vs. 4% (p = 0.006) respectively. CONCLUSION: With increasing experience, more patients were accepted for complex hepatectomies. However, there was a definite yet contained increase in postoperative morbidity and mortality.

Living or Brain-dead Donor Liver Transplantation for Hepatocellular Carcinoma: A Multicenter, Western, Intent-to-treat Cohort Study.

OBJECTIVE: An intent-to-treat analysis of overall survival (ITT-OS) of cirrhotic patients with hepatocellular carcinoma (HCC) listed for living donor liver transplantation (LDLT) or brain-dead donor liver transplantation (BDLT) across 5 French liver transplant (LT) centers. BACKGROUND: Comparisons of HCC outcomes after LDLT and BDLT measured from time of transplantation have yielded conflicting results. METHODS: Records from 861 cirrhotic patients with HCC consecutively listed for either LDLT (n = 79) or BDLT (n = 782) from 2000 to 2009 were analyzed for ITT-OS using a Cox model; and tumor recurrence using 2 competitive risk models. RESULTS: Tumor staging was similar between groups. In total, 162 patients dropped out (20.7%), all from Group BDLT (P < 0.0001). The postoperative mortality rate and the retransplantation rate were similar between LDLT and BDLT. At 5 years, no statistically significant difference was found in ITT-OS between LDLT and BDLT groups (73.2% vs 66.7%; P = 0.062). LDLT waitlist inclusion (hazard ratio: 0.61 (0.39-0.96); P = 0.034) and a time-of-listing MELD score ≥ 25 (hazard ratio: 1.93 (1.15-3.26); P = 0.014) were independent predictors of ITT-OS. Similar 5-year post-LT OS rates (73.2% and 73.0% for Group LDLT and Group BDLT, respectively; P = 0.407) and HCC recurrence rates (10.9% and 11.2% for Group LDLT and Group BDLT, respectively; P = 0.753) were found. Upon explant analysis, tumors exceeding the Milan criteria, macroscopic vascular invasion, and AFP score>2 were independent predictors of recurrence, whereas LT type was not. CONCLUSIONS: LDLT improves ITT-OS, and it is not a risk factor for tumor recurrence. Therefore, LDLT and BDLT should be equally encouraged in countries where both are available.

Complex Liver Resection Using Standard Total Vascular Exclusion, Venovenous Bypass, and In Situ Hypothermic Portal Perfusion: An Audit of 77 Consecutive Cases.

OBJECTIVE: To identify independent predictors of 90-day mortality after liver resection for patients undergoing standard total vascular exclusion (TVE) with hypothermic portal perfusion and venovenous bypass. The secondary endpoint was to evaluate the long-term outcomes. BACKGROUND: Tumors invading the vena cava and/or the hepatocaval confluence are indications for standard TVE. The inclusion of liver hypothermic perfusion permits safe TVE. There are a limited number of reports focusing on this complex technique and no relevant analysis of short-term and long-term results. METHODS: Seventy-seven consecutive liver resections performed using standard TVE with hypothermic portal perfusion and venovenous bypass between 1998 and 2010 were analyzed. The independent predictors and rates of 90-day mortality, morbidity, and long-term survival were evaluated. RESULTS: The 90-day mortality rate was 19.5% (15 cases). Three independent predictors of mortality were identified: age-adjusted Charlson Comorbidity Index 3 or more (P = 0.0231; odds ratio = 47.565; 95% confidence interval = 1.701-1330.414), tumor size 10 cm or more (P = 0.0442; odds ratio = 6.374; 95% confidence interval = 1.049-38.734), and the presence of 50/50 criteria (P = 0.0407; odds ratio = 6.217; 95% confidence interval = 1.080-35.782). The overall 5-year survival rate was 30.4%. CONCLUSIONS: Liver resection using standard TVE with hypothermic portal perfusion and venovenous bypass is associated with a high mortality rate. The identification of preoperative predictors of mortality should improve the selection of patients for this aggressive surgery. Compared with nonsurgical management, the long-term results are acceptable and justify this aggressive surgery in selected patients.

Portal vein arterialization: a salvage procedure for a totally de-arterialized liver. The Paul Brousse Hospital experience.

BACKGROUND: Portal vein arterialization (PVA) has been used as a salvage inflow technique when hepatic artery (HA) reconstruction is deemed impossible in liver transplantation (LT) or hepatopancreatobiliary (HPB) surgery. Outcomes and the management of possible complications have not been well described. METHODS: The present study analysed outcomes in 16 patients who underwent PVA during the period from February 2005 to January 2011 for HA thrombosis post-LT (n = 7) or after liver resection (n = 1), during curative resection for locally advanced HPB cancers (requiring HA interruption) (n = 7) and for HA resection without reconstruction (n = 1). In addition, a literature review was conducted. RESULTS: Nine patients were women. The median age of the patients was 58 years (range: 30-72 years). Recovery of intrahepatic arterial signals and PVA shunt patency were documented using Doppler ultrasound until the last follow-up (or until shunt thrombosis in some cases). Of five postoperative deaths, two occurred as a result of haemorrhagic shock, one as a result of liver ischaemia and one as a result of sepsis. The fifth patient died at home of unknown cause. Three patients (19%) had major bleeding related to portal hypertension (PHT). Of these, two underwent re-exploration and one underwent successful shunt embolization to control the bleeding. Four patients (25%) had early shunt thrombosis, two of whom underwent a second PVA. After a median follow-up of 13 months (range: 1-60 months), 10 patients (63%) remained alive with normal liver function and one submitted to retransplantation. CONCLUSIONS: Portal vein arterialization results in acceptable rates of survival in relation to spontaneous outcomes in patients with completely de-arterialized livers. The management of complications (especially PHT) after the procedure is challenging. Portal vein arterialization may represent a salvage option or a bridge to liver retransplantation and thus may make curative resection in locally advanced HPB cancers with vascular involvement feasible.

Caval inflow to the graft for liver transplantation in patients with diffuse portal vein thrombosis: a 12-year experience.

OBJECTIVE: To analyze the short- and long-term results of cavoportal anastomosis (CPA) and renoportal anastomosis (RPA) in 20 consecutive liver transplantation (LT) candidates with diffuse portal vein thrombosis (PVT). SUMMARY BACKGROUND DATA: Caval inflow to the graft (CIG) by CPA or RPA has been the most commonly used salvage technique to overcome the absolute contraindication for LT in case of diffuse PVT. METHODS: From 1996 to 2009, 3 patients (15%) underwent CPA and 17 patients (85%) had an RPA during LT. In addition to routine follow-up, patients were specifically evaluated for signs of portal hypertension (PHT) and for patency of the anastomoses. The follow-up ranged from 3 months to 12 years (median of 4.5 years). RESULTS: : Caval inflow to the graft was feasible in all attempted cases. In the short term (<6 months), 35% of patients had residual PHT-related complications (massive ascites and variceal bleeding). These resolved spontaneously or with endoscopic management. Three deaths occurred; none was related to PHT or shunt thrombosis. In the long term (>6 months), 1 death occurred because of recurrent variceal bleeding after RPA thrombosis. At last follow-up, all living patients [n = 13 (65%)] had normal liver function, no signs of PHT and patent anastomoses. There were no retransplantations. Graft and patient survival at 1, 3, and 5 years were 83%, 75%, and 60%, respectively. CONCLUSIONS: Caval inflow to the graft is an efficacious salvage technique with satisfactory long-term results, considering the spontaneous outcome in patients denied LT because of diffuse PVT. Adequate preoperative management of PHT and its associated complications is vital in obtaining good results. In the long term, residual PHT resolves and the liver function returns to normal.

Short- and long-term results of extended left hepatectomy for colorectal metastases.

BACKGROUND: An extended left hepatectomy is a complex hepatic resection often performed for large tumours in close relationship to major hilar structures. Operative outcomes of this resection for colorectal liver metastases (CLM) remain unclear. The aim of the present study was to assess short- and long-term outcome for patients with CLM after an extended left hepatectomy. METHODS: A retrospective analysis of consecutive patients undergoing an extended left hepatectomy for CLM in a large, single-centre cohort between January 1990 and January 2006 was performed. RESULTS: Thirty-one patients (3.9%) from a consecutive series of 802 patients who had undergone hepatic resection were identified as having met the definition of an extended left hepatectomy and were included for further analysis. Maximum tumour size was more than 60 mm in 15 patients, with a median size of 67.5 mm for the total group (range: 20 to 160 mm). Twenty-six patients presented with initially unresectable metastases, related to large tumour size in 11 patients and to a close relation with major vascular structures in six patients. Preoperative chemotherapy was administered to 29 patients. Combined vascular resection was performed in five patients. The mortality rate at 90 days was zero and post-operative morbidity occurred in 17 patients. R0 and R1 resections were performed in 17 and 11 patients, respectively. Three- and 5-year overall survival was 38% and 27%, respectively. Disease-free survival was 9% and 4% at 3 and 5 years. Morbidity did not differ between patients with and without a caudate lobectomy (9 of 17 patients vs. 8 of 14 patients, respectively) (P= 0.815). CONCLUSIONS: An extended left hepatectomy for CLM can provide significant long-term survival. However, morbidity is increased in this complex procedure. A caudate lobectomy does not impact surgical outcome.

Intention-to-treat analysis of liver transplantation for hepatocellular carcinoma: living versus deceased donor transplantation.

UNLABELLED: For patients who have cirrhosis with hepatocellular carcinoma (HCC), living donor liver transplantation (LDLT) reduces waiting time and dropout rates. We performed a comparative intention-to-treat analysis of recurrence rates and survival outcomes after LDLT and deceased donor liver transplantation (DDLT) in HCC patients. Our study included 183 consecutive patients with HCC who were listed for liver transplantation over a 9-year period at our institution. Tumor recurrence was the primary endpoint. At listing, patient and tumor characteristics were comparable in the two groups (LDLT, n = 36; DDLT, n = 147). Twenty-seven (18.4%) patients dropped out, all from the DDLT waiting list, mainly due to tumor progression (19/27 [70%] patients). The mean waiting time was shorter in the LDLT group (2.6 months versus 7.9 months; P = 0.001). The recurrence rates in the two groups were similar (12.9% and 12.7%, P = 0.78), and there was a trend toward a longer time to recurrence after LDLT (38 ± 27 months versus 16 ± 13 months, P = 0.06). Tumors exceeding the University of California, San Francisco (UCSF) criteria, tumor grade, and microvascular invasion were independent predictive factors for recurrence. On an intention-to-treat basis, the overall survival (OS) in the two groups was comparable. Patients beyond the Milan and UCSF criteria showed a trend toward worse outcomes with LDLT compared with DDLT (P = 0.06). CONCLUSION: The recurrence and survival outcomes after LDLT and DDLT were comparable on an intent-to-treat analysis. Shorter waiting time preventing dropouts is an additional advantage with LDLT. LDLT for HCC patients beyond validated criteria should be proposed with caution.

Impact of expanding criteria for resectability of colorectal metastases on short- and long-term outcomes after hepatic resection.

BACKGROUND: An expansion of resectability criteria of colorectal liver metastases (CLM) is justified provided "acceptable" short-term and long-term outcomes. The aim of the present study was to ascertain this paradigm in an era of modern liver surgery. METHODS: All consecutive patients who underwent hepatic resection for CLM at our institute between 1990 and 2010 were included in the study. Ninety-day mortality and morbidity rates were determined in the total study population and in 2 separate time periods (group I: 1990-2000; group II: 2000-2010). Similarly, overall and progression-free survival rates were determined. Independent predictors of postoperative morbidity were identified at multivariate analysis. RESULTS: Between 1990 and 2010, 1394 hepatectomies were performed in 1028 patients. Overall perioperative mortality and postoperative morbidity rates were 1.3% and 33%, respectively. Although patients in group II were older, had more often comorbid illnesses, and presented with more extensive liver disease, similar perioperative mortality rates were observed (1.1% in group I and 1.4% in group II; P = 0.53). A trend toward a higher morbidity rate was observed in group II (34% vs 31% in group I; P = 0.16). Independent predictors of postoperative morbidity were: treatment between 2000 and 2010, total hepatic ischemia time of 60 minutes or more, maximum size of CLM of 30 mm or more at histopathology, and presence of abnormalities in the nontumoral liver parenchyma. Although a trend toward lower overall survival was observed in patients with significant postoperative complications, no significant differences were observed in long-term outcomes between both treatment periods. CONCLUSION: After an aggressive multidisciplinary treatment of CLM, acceptable overall mortality and morbidity rates were observed. Perioperative mortality rates did not differ according to treatment period; however, more recently operated patients experienced more postoperative complications. These favorable short-term outcomes, without worsening of long-term outcomes, justify an expansion of the criteria for resectability in this patient category.

Ischaemic preconditioning of the graft in adult living related right lobe liver transplantation: impact on ischaemia-reperfusion injury and clinical relevance.

BACKGROUND: Ischaemic preconditioning (IPC) of the right liver graft in the donor has not been studied in adult-to-adult living related liver transplantation (LRLT). OBJECTIVE: To assess the IPC effect of the graft on ischaemia reperfusion injury in the recipient and compare recipient and donor outcomes with and without preconditioned grafts. PATIENTS AND METHODS: Alternate patients were transplanted with right lobe grafts that were (n = 22; Group (Precond)) or were not (n = 22; Group (Control)) subjected to IPC in the living donor. Liver ischaemia-reperfusion injury, liver/kidney function, morbidity/mortality rates and outcomes were compared. Univariate and multivariate analyses were performed to identify factors predictive of the aspartate aminotransferase (AST) peak and minimum prothrombin time. RESULTS: Both groups had similar length of hospital stay, morbidity/mortality, primary non-function and acute rejection rates. Post-operative AST (P = 0.8) and alanine aminotransferase (ALT) peaks (P = 0.6) were similar in both groups (307 +/- 189 and 437 +/- 302 vs. 290 +/- 146 and 496 +/- 343, respectively). In univariate analysis, only pre-operative AST and warm ischemia time (WIT) were significantly associated with post-operative AST peak (in recipients). In multivariate analysis, the graft/recipient weight ratio (P = 0.003) and pre-operative bilirubin concentration (P = 0.004) were significantly predictive of minimum prothrombin time post-transplantation. CONCLUSIONS: Graft IPC in the living related donor is not associated with any benefit for the recipient or the donor and its clinical value remains uncertain.

Long-term outcomes after hepatic resection for colorectal metastases in young patients.

BACKGROUND: Long-term outcomes after hepatectomy for colorectal liver metastases in relatively young patients are still unknown. The aim of the current study was to evaluate long-term outcomes in patients < or = 40 years old, and to compare them with patients >40 years old. METHODS: All consecutive patients who underwent hepatectomy for colorectal liver metastases at the authors' hospital between 1990 and 2006 were included in the study. Patients < or = 40 years old were compared with all other patients treated during the same period. Overall survival (OS), progression-free survival (PFS), and disease-free survival (DFS) rates were determined, and prognostic factors were identified. RESULTS: In total, 806 patients underwent hepatectomy for colorectal liver metastases, of whom 56 (7%) were aged < or = 40 years. Among the young patients, more colorectal liver metastases were present at diagnosis, and they were more often diagnosed synchronous with the primary tumor. Five-year OS was 33% in young patients, compared with 51% in older patients (P = .12). Five-year PFS was 2% in young patients, compared with 16% in older patients (P < .001). DFS rates were comparable between the groups (17% vs 23%, P = .10). At multivariate analysis, age < or = 40 years was identified as an independent predictor of poor PFS. CONCLUSIONS: In young patients, colorectal liver metastases seem to be more aggressive, with a trend toward lower OS, more disease recurrences, and a significantly shorter PFS after hepatectomy. However, DFS rates were comparable between young and older patients, owing to an aggressive multimodality treatment approach, consisting of chemotherapy and repeat surgery. Therefore, physicians should recognize the poor outcome of colorectal liver metastases in young patients and should consider an aggressive approach to diagnosis and early treatment.

Combined liver resection and reconstruction of the supra-renal vena cava: the Paul Brousse experience.

BACKGROUND: Liver tumors with inferior vena cava (IVC) involvement may require combined resection of the liver and IVC. This approach, with its high surgical risks and poor long-term prognosis, was precluded until the development of neoadjuvant chemotherapy, portal vein embolization, reinforced vascular prostheses, and technical advances in liver transplantation. METHODS: We reviewed 22 cases of hepatectomy with retrohepatic IVC resection and reconstruction. The patients had a median age of 51.5 years (range, 32.8-75.3 years). Indications for resection were: liver metastases (n = 9), cholangiocarcinoma (n = 8), hepatocellular carcinoma (n = 2), other cancers (n = 3). The liver resections carried out included 18 first, 3 second, and one third hepatectomy. Segment 1 (caudate lobe) was included in the specimen in 19 cases (86%). Resection concerned 1 to 6 liver segments (median = 5.0). Vascular control was achieved by vascular exclusion of the liver preserving the caval flow (n = 1), standard vascular exclusion of the liver (n = 12), in situ cold perfusion of the liver (n = 9). Ex situ surgery was not necessary in any case. Venovenous bypass was used in 12 cases. The IVC was reconstructed with a ringed Gore-Tex tube graft (n = 10), primarily (n = 8), or by caval plasty (n = 4). A main hepatic vein was reimplanted in 6 cases: into the native IVC (n = 4) or into a Gore-Tex tube graft (n = 2). RESULTS: One patient died (4.5%) due to catheter infection, 7 days after in situ cold perfusion with replacement of the vena cava. Eight patients (36%) had no complications and 14 patients (64%) had 23 complications. In all but 1 case, the complications were transient and successfully controlled. The patients stayed in intensive care for 3.3 +/- 2.0 days and in the hospital for 17.7 +/- 7.8 days. All vascular reconstructions were patent at last follow-up. With median follow-up of 19 months, 10 patients died of tumor recurrence and eleven were alive with (n = 5) or without (n = 6) disease. Actuarial 1-, 3-, and 5-year survival rates were 81.8%, 38.3%, and 38.3%, respectively. CONCLUSIONS: IVC resection and reconstruction combined with liver resection can be safely performed in selected patients. The lack of alternative treatments and the spontaneous poor prognosis justify this approach, provided that surgery is carried out at a center specialized in both liver surgery and liver transplantation. The development of adjuvant chemotherapy regimens is required to improve the long-term results of this salvage surgery.

Ischemic preconditioning for major liver resection under vascular exclusion of the liver preserving the caval flow: a randomized prospective study.

BACKGROUND: Two randomized prospective studies suggested that ischemic preconditioning (IP) protects the human liver against ischemia-reperfusion injury after hepatectomy performed under continuous clamping of the portal triad. The primary goal of this study was to determine whether IP protects the human liver against ischemia-reperfusion injury after hepatectomy under continuous vascular exclusion with preservation of the caval flow. STUDY DESIGN: Sixty patients were randomly divided into two groups: with (n=30; preconditioning group) and without (n=30; control group) IP (10 minutes of portal triad clamping and 10 minutes of reperfusion) before major hepatectomy under vascular exclusion of the liver preserving the caval flow. Serum concentrations of aspartate transferase, alanine transferase, glutathione-S-transferase, and bilirubin and prothrombin time were regularly determined until discharge and at 1 month. Morbidity and mortality were determined in both groups. RESULTS: Peak postoperative concentrations of aspartate transferase were similar in the groups with and without IP (851 +/- 1,733 IU/L and 427 +/- 166 IU/L respectively, p=0.2). A similar trend toward a higher peak concentration of alanine transferase and glutathione-S-transferase was indeed observed in the preconditioning group compared with the control group. Morbidity and mortality rates and lengths of ICU and hospitalization stays were similar in both groups. CONCLUSIONS: IP does not improve liver tolerance to ischemia-reperfusion after hepatectomy under vascular exclusion of the liver with preservation of the caval flow. This maneuver does not improve postoperative liver function and does not affect morbidity or mortality rates. The clinical use of IP through 10 minutes of warm ischemia in this technique of hepatectomy is not currently recommended.

Effects of 10 minutes of ischemic preconditioning of the cadaveric liver on the graft's preservation and function: the ying and the yang.

SUMMARY BACKGROUND DATA: Although extensively studied in animal models, ischemic preconditioning has not yet been studied in clinical transplantation. OBJECTIVE: To compare the results of cadaveric liver transplantation with and without ischemic liver preconditioning in the donor. PATIENTS AND METHODS: Alternate patients were transplanted with liver grafts that had (n = 46, GroupPrecond) or had not (n = 45, GroupControl) been subjected to ischemic preconditioning. Liver ischemia-reperfusion injury, liver and kidney function, morbidity, and in-hospital mortality rates were compared in the 2 groups. Initial poor function was defined as a minimal prothrombin time within 10 days of transplantation <30% of normal and/or bilirubin >200 micromol/L. RESULTS: The postoperative peaks of ASAT (IU/L) and ALAT (IU/L) were significantly lower in GroupPrecond (556 +/- 968 and 461+/-495, respectively) than in the GroupControl (1073 +/- 1112 and 997+/-1071, respectively). The rate of technical morbidity and the incidence of acute rejection were similar in both groups. Initial poor function was significantly more frequent in the GroupPrecond (10 of 46 cases) than in the GroupControl (3 of 45 cases). Hospital mortality rates were similar in the 2 groups. In multivariate analysis, body mass index of the donor, graft steatosis, and ischemic preconditioning were significantly predictive of the posttransplant peak of ASAT. In univariate analysis, only preconditioning was significantly associated with initial poor function. CONCLUSIONS: Compared with standard orthotopic liver transplant, ischemic preconditioning of the liver graft in the donor is associated with better tolerance to ischemia. However, this is at the price of decreased early function. Until further studies are available, the clinical value of preconditioning liver grafts remains uncertain.

In situ hypothermic perfusion of the liver versus standard total vascular exclusion for complex liver resection.

SUMMARY BACKGROUND DATA: We compare the results of liver resection performed under in situ hypothermic perfusion versus standard total vascular exclusion (TVE) of the liver <60 minutes and > or =60 minutes in terms of liver tolerance, liver and renal functions, postoperative morbidity, and mortality. The safe duration of TVE is still debated. Promising results have been reported following TVE associated with hypothermic perfusion of the liver with durations of up to several hours. The 2 techniques have not been compared so far. METHODS: The study population includes 69 consecutive liver resections under TVE <60 minutes (group TVE<60', 33 patients), > or =60 minutes (group TVE> or =60', 16 patients), and in situ hypothermic perfusion (group TVEHYOPOTH, 20 patients). Liver tolerance (peaks of transaminases), liver and kidney function (peak of bilirubin, minimum prothrombin time, and peak of creatinine), morbidity, and in-hospital mortality were compared within the 3 groups. RESULTS: The postoperative peaks of aspartate aminotransferase (IU/L) and alanine aminotransferase (IU/L) were significantly lower (P[r] < 0.05) in group TVE HYPOTH (450 +/- 298 IU/L and 390 +/- 391 IU/L) compared with the groups TVE<60' (1000 +/- 808; 853 +/- 743) and TVE> or =60' (1519 +/- 962; 1033 +/- 861). In the group TVEHYPOTH, the peaks of bilirubin (micromol/L) (84 +/- 31), creatinine (micromol/L) (75 +/- 22), and the number of complications per patient (1.2 +/- 0.9) were comparable to those of the group TVE<60' (80 +/- 111; 109 +/- 77; and 0.8 +/- 1.1 respectively) and significantly lower to those of the group TVE> or =60' (196 +/- 173; 176 +/- 176, and 2.6 +/- 1.8). In-hospital mortality rates were 1 in 33, 2 in 16, and 0 in 20 for the groups TVE<60', TVE> or =60', and TVEHYOPOTH, respectively, and were comparable. On multivariate analysis, the size of the tumor, portal vein embolization, and a planned vascular reconstruction were significantly predictive of TVE > or =60 minutes. CONCLUSIONS: Compared with standard TVE of any duration, hypothermic perfusion of the liver is associated with a better tolerance to ischemia. In addition, compared with TVE > or =60 minutes, it is associated with better postoperative liver and renal functions and a lower morbidity. Predictive factors for TVE > or =60 minutes may help to indicate hypothermic perfusion of the liver.