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Adjuvant chemotherapy (AC) can prolong overall survival (OS) after pancreatoduodenectomy (PD) for pancreatic ductal adenocarcinoma (PDAC). However, fitness for AC may be influenced by postoperative recovery. We aimed to investigate if serious (Clavien-Dindo grade ≥ IIIa) postoperative complications affected AC rates, disease recurrence and OS. Data were extracted from the Recurrence After Whipple's (RAW) study (n = 1484), a retrospective study of PD outcomes (29 centres from eight countries). Patients who died within 90-days of PD were excluded. The Kaplan-Meier method was used to compare OS in those receiving or not receiving AC, and those with and without serious postoperative complications. The groups were then compared using univariable and multivariable tests. Patients who commenced AC (vs no AC) had improved OS (median difference: (MD): 201 days), as did those who completed their planned course of AC (MD: 291 days, p < 0.0001). Those who commenced AC were younger (mean difference: 2.7 years, p = 0.0002), more often (preoperative) American Society of Anesthesiologists (ASA) grade I-II (74% vs 63%, p = 0.004) and had less often experienced a serious postoperative complication (10% vs 18%, p = 0.002). Patients who developed a serious postoperative complication were less often ASA grade I-II (52% vs 73%, p = 0.0004) and less often commenced AC (58% vs 74%, p = 0.002). In our multicentre study of PD outcomes, PDAC patients who received AC had improved OS, and those who experienced a serious postoperative complication commenced AC less frequently. Selected high-risk patients may benefit from targeted preoperative optimisation and/or neoadjuvant chemotherapy. [ABSTRACT FROM AUTHOR]

Purpose: To compare the size of ablation zones derived from nonperfused ex vivo livers with ablation zones created using an ex vivo perfused porcine liver model.Materials and Methods: Six fresh porcine livers were used to evaluate microwave ablation (MWA). Perfused (n = 3) and nonperfused (n = 3) livers were warmed to 37°C by oxygenated, O-positive human blood reconstituted with Ringer solution, using an organ perfusion circuit. During MWA, perfusion was discontinued in the nonperfused group and maintained in the perfused group. After MWA (140 watts × 2 min at 2.45 GHz) with the Acculis MTA System (AngioDynamics, Latham, New York), ablation zones were bisected sagittally. Sections were stained with nicotinamide adenine dinucleotide (NADH) and hematoxylin-eosin to assess viability of cells in ablation and marginal zones.Results: Comparison of 22 MWA zones (9 in perfused group, 13 in nonperfused group) was performed. Ablation zones demonstrated a central "white" and peripheral "red" zone. Cells in the white zone were nonviable with no NADH staining. The red zone showed progressive NADH staining toward the periphery, suggesting incomplete cell death. White and red zones of the perfused group were significantly smaller compared with the nonperfused group (short axis, 17.8 mm ± 2.7 vs 21.1 mm ± 3.2, P = .003; long axis, 40.69 mm ± 3.9 vs 39.63 mm ± 5.2, P = .44; intermediate zone,1.33 mm ± 0.04 vs 2.7 mm ± 0.14, P < .0001; mean ± SD).Conclusions: MWA algorithms provided by this manufacturer are based on nonperfused organ data, which overestimate ablation zone size. Data from perfused liver models may be required for more accurate dosimetry guidelines. [ABSTRACT FROM AUTHOR]

Objective This study sought to compare the perioperative outcomes of interventions aiming to decrease ischemia–reperfusion (IR) injury during elective liver resection. Method A comprehensive literature search was performed to identify randomized controlled trials. A Bayesian network metaanalysis was performed using the Markov chain Monte Carlo method in WinBUGS following the guidelines of the National Institute for Health and Clinical Excellence Decision Support Unit. Odds ratios for binary outcomes and mean differences for continuous outcomes were calculated using a fixed effect model or a random effects model according to model fit. Results Forty-four trials with 2,457 patients having undergone liver resection were included and were divided into 8 classes of interventions aimed at decreasing IR injury and a control group, which was hepatectomy alone. There was no difference between the different interventions in mortality, quantity of blood transfusion, and durations of stay in an intensive therapy unit between any pairwise comparisons. Patients treated with ischemic preconditioning, cardiovascular modulators, and miscellaneous interventions had significantly fewer serious adverse events compared with patients undergoing liver resection alone. Ischemic preconditioning patients had significantly fewer transfusion proportions and shorter operative time than patients treated with steroids. Ischemic preconditioning had significantly less operative blood loss compared with all other interventions, and a lesser duration of hospital stay than hepatectomy alone. Sensitivity analysis showed that the drugs sevoflurane (a volatile anesthetic), verapamil (a calcium channel blocker), and gabexate mesilate (a thrombin inhibitor) produced fewer serious adverse events compared with hepatectomy alone. Conclusion Ischemic preconditioning resulted in multiple beneficial clinical endpoints and further RCTs seem to be needed to confirm its clinical benefits. [ABSTRACT FROM AUTHOR]

Purpose: To assess the safety and tolerability of a vandetanib-eluting radiopaque embolic (BTG-002814) for transarterial chemoembolization (TACE) in patients with resectable liver malignancies.Materials and Methods: The VEROnA clinical trial was a first-in-human, phase 0, single-arm, window-of-opportunity study. Eligible patients were aged ≥18 years and had resectable hepatocellular carcinoma (HCC) (Child-Pugh A) or metastatic colorectal cancer (mCRC). Patients received 1 mL of BTG-002814 transarterially (containing 100 mg of vandetanib) 7-21 days prior to surgery. The primary objectives were to establish the safety and tolerability of BTG-002814 and determine the concentrations of vandetanib and the N-desmethyl vandetanib metabolite in the plasma and resected liver after treatment. Biomarker studies included circulating proangiogenic factors, perfusion computed tomography, and dynamic contrast-enhanced magnetic resonance imaging.Results: Eight patients were enrolled: 2 with HCC and 6 with mCRC. There was 1 grade 3 adverse event (AE) before surgery and 18 after surgery; 6 AEs were deemed to be related to BTG-002814. Surgical resection was not delayed. Vandetanib was present in the plasma of all patients 12 days after treatment, with a mean maximum concentration of 24.3 ng/mL (standard deviation ± 13.94 ng/mL), and in resected liver tissue up to 32 days after treatment (441-404,000 ng/g). The median percentage of tumor necrosis was 92.5% (range, 5%-100%). There were no significant changes in perfusion imaging parameters after TACE.Conclusions: BTG-002814 has an acceptable safety profile in patients before surgery. The presence of vandetanib in the tumor specimens up to 32 days after treatment suggests sustained anticancer activity, while the low vandetanib levels in the plasma suggest minimal release into the systemic circulation. Further evaluation of this TACE combination is warranted in dose-finding and efficacy studies. [ABSTRACT FROM AUTHOR]

Abstract: Portal hypertension is defined as portal venous pressure exceeding 10 mmHg. Because direct measurement of portal venous pressure is impractical, it is usually estimated indirectly by measurement of the wedged hepatic vein pressure, corrected for the inferior vena caval pressure. [Copyright &y& Elsevier]

Tissue-resident memory T cells have critical roles in long-term pathogen and tumor immune surveillance in the liver. We investigate the role of autophagy in equipping human memory T cells to acquire tissue residence and maintain functionality in the immunosuppressive liver environment. By performing ex vivo staining of freshly isolated cells from human liver tissue, we find that an increased rate of basal autophagy is a hallmark of intrahepatic lymphocytes, particularly liver-resident CD8+ T cells. CD8+ T cells with increased autophagy are those best able to proliferate and mediate cytotoxicity and cytokine production. Conversely, blocking autophagy induction results in the accumulation of depolarized mitochondria, a feature of exhausted T cells. Primary hepatic stellate cells or the prototypic hepatic cytokine interleukin (IL)-15 induce autophagy in parallel with tissue-homing/retention markers. Inhibition of T cell autophagy abrogates tissue-residence programming. Thus, upregulation of autophagy adapts CD8+ T cells to combat mitochondrial depolarization, optimize functionality, and acquire tissue residence. • An increased rate of basal autophagy is a hallmark of liver-resident CD8+ T cells • Enhanced T cell autophagy can be imprinted by IL-15 or hepatic stellate cells • Autophagy induction is required for tissue-residence programming in vitro • Enhanced autophagy maintains T RM mitochondrial fitness in the liver Swadling et al. show that an increased rate of basal autophagy is a hallmark of intrahepatic lymphocytes, particularly liver-resident CD8+ T cells and that in vitro T RM programming requires autophagy induction. Upregulation of autophagy adapts CD8+ T cells to combat mitochondrial depolarization, optimize functionality, and acquire tissue residence. [ABSTRACT FROM AUTHOR]

Diabetes mellitus (DM) has a complex relationship with pancreatic cancer. This study examines the impact of preoperative DM, both recent-onset and pre-existing, on long-term outcomes following pancreatoduodenectomy (PD) for pancreatic ductal adenocarcinoma (PDAC). Data were extracted from the Recurrence After Whipple's (RAW) study, a multi-centre cohort of PD for pancreatic head malignancy (2012–2015). Recurrence and five-year survival rates of patients with DM were compared to those without, and subgroup analysis performed to compare patients with recent-onset DM (less than one year) to patients with established DM. Out of 758 patients included, 187 (24.7%) had DM, of whom, 47 of the 187 (25.1%) had recent-onset DM. There was no difference in the rate of postoperative pancreatic fistula (DM: 5.9% vs no DM 9.8%; p = 0.11), five-year survival (DM: 24.1% vs no DM: 22.9%; p = 0.77) or five-year recurrence (DM: 71.7% vs no DM: 67.4%; p = 0.32). There was also no difference between patients with recent-onset DM and patients with established DM in postoperative outcomes, recurrence, or survival. We found no difference in five-year recurrence and survival between diabetic patients and those without diabetes. Patients with pre-existing DM should be evaluated for PD on a comparable basis to non-diabetic patients. [ABSTRACT FROM AUTHOR]

Nutritional problems are common in patients requiring liver transplantation. Recipient obesity or malnutrition are thought to increase postoperative complications. Body mass index (BMI) is commonly used prior to major surgery but its value specifically in liver transplant assessment has not been established. This is a retrospective study assessing the correlation between the BMI of individuals undergoing liver transplant and the development of postoperative infectious complications. Data were collected from a prospectively maintained database regarding all consecutive patients over a period of 23 years. Preoperative recipient BMI was correlated with the number, nature and outcome of postoperative infective complications. Of a total of 1156 consecutive patients, 13.2% developed infectious complications. Thirty-day mortality was 7.2% and 90-day mortality was 10%. Higher BMI was associated with higher risk of infections (p = 0.002). Wound infections occurred predominantly in obese patients (p = 0.001) while other types of infections were more common in malnourished patients (p < 0.001). Extremes of BMI are associated with increased infectious complications following liver transplantation. Patients with lower BMI had a higher rate of overall infectious complications whereas those with a higher BMI had increased general and wound complications. [ABSTRACT FROM AUTHOR]

Pancreatoduodenectomy (PD) is recommended in fit patients with a resectable ampullary adenocarcinoma (AA). We aimed to identify predictors of five-year recurrence/survival. Data were extracted from the Recurrence After Whipple's (RAW) study, a multicentre retrospective study of PD patients with a confirmed head of pancreas or periampullary malignancy (June 1st, 2012–May 31st, 2015). Patients with AA who developed recurrence/died within five-years were compared to those who did not. 394 patients were included and actual five-year survival was 54%. Recurrence affected 45% and the median time-to-recurrence was 14 months. Local only, local and distant, and distant only recurrence affected 34, 41 and 94 patients, respectively (site unknown: 7). Among those with recurrence, the most common sites were the liver (32%), local lymph nodes (14%) and lung/pleura (13%). Following multivariable tests, number of resected nodes, histological T stage > II, lymphatic invasion, perineural invasion (PNI), peripancreatic fat invasion (PPFI) and ≥1 positive resection margin correlated with increased recurrence and reduced survival. Furthermore, ≥1 positive margin, PPFI and PNI were all associated with reduced time-to-recurrence. This multicentre retrospective study of PD outcomes identified numerous histopathological predictors of AA recurrence. Patients with these high-risk features might benefit from adjuvant therapy. [ABSTRACT FROM AUTHOR]

Novel hepatoprotective strategies are needed to improve clinical outcomes during liver surgery. There is mixed data on the role of remote ischemic preconditioning (RIPC). We investigated RIPC in partial hepatectomy for primary hepatocellular carcinoma (HCC). This was a Phase II, single-center, sham-controlled, randomized controlled trial (RCT). The primary hypothesis was that RIPC would reduce acute liver injury following surgery indicated by serum alanine transferase (ALT) 24 h following hepatectomy in patients with primary HCC, compared to sham. Patients were randomized to receive either four cycles of 5 min/5 min arm cuff inflation/deflation immediately prior to surgery, or sham. Secondary endpoints included clinical, biochemical and pathological outcomes. Liver function measured by Indocyanine Green pulse densitometry was performed in a subset of patients. 24 and 26 patients were randomized to RIPC and control groups respectively. The groups were balanced for baseline characteristics, except the duration of operation was longer in the RIPC group. Median ALT at 24 h was similar between groups (196 IU/L IQR 113.5–419.5 versus 172.5 IU/L IQR 115–298 respectively, p = 0.61). Groups were similar in secondary endpoints. This RCT did not demonstrate beneficial effects with RIPC on serum ALT levels 24 h after partial hepatectomy. [ABSTRACT FROM AUTHOR]

Accurate assessment of steatosis in procured livers is crucial to reduce the poor outcome associated with high-grade steatosis and to optimize the utilization of donor grafts. Clinical examination and digital image analysis (DIA) have been used for steatosis evaluation, but the validity of these methods is debated. This study aimed to compare these methods with standard histology for assessment of steatosis severity in human livers and to evaluate a revised classification system for automated fat measurement. Clinical assessment of liver steatosis at time of retrieval and automated measurement were compared with standard histology in paraffinized and hematoxylin and eosin–stained slides, using a 4-grade scale for ordinal data and percentages for numerical values. Analysis of 42 human livers that were retrieved but not transplanted showed that clinical examination was not reliable for assigning steatosis grades (κ w , 0.12; 95% CI, −0.06 to 0.30), overestimated steatosis severity, and had an accuracy of 67% for discriminating low- and high-grade steatosis. Digital image analysis had a substantial agreement on absolute fat percentage (intraclass correlation coefficient, 0.76; 95% CI, 0.63–0.84) and steatosis grades (κ w , 0.70; 95% CI, 0.57–0.82), with 88% accuracy using the revised classification system. Clinical assessment of steatosis is inaccurate, and relying on this method alone could result in unnecessary discard of livers. Digital image analysis is feasible with higher accuracy and reliability, but further clinical studies are required to evaluate its clinical validity. • Forty-two deceased donor human livers, which were retrieved but not transplanted, were evaluated for steatosis severity comparing clinical examination at the time of procurement, digital image analysis, and standard pathologic assessment. • Clinical examination was not reliable for assigning steatosis grades (κ w , 0.12; 95% CI, −0.06 to 0.30), overestimated steatosis severity, and had an accuracy of 67% for discriminating low- and high-grade steatosis. • Using a revised steatosis grading system, digital image analysis had a substantial agreement on the absolute fat percentage (intraclass correlation coefficient, 0.76; 95% CI, 0.63–0.84) and steatosis grades (κ w , 0.70; 95% CI, 0.57–0.82), with 88% accuracy for discriminating low- and high-grade steatosis. • There was no significant difference in steatosis severity using 2 different biopsy sites, which indicates adequacy of single biopsies for steatosis assessment and reduces the risk of parenchymal injury due to multiple biopsies. [ABSTRACT FROM AUTHOR]

Soluble CD163 (sCD163), a macrophage activation marker, is upregulated in conditions of macrophage proliferation and activation. Elevated sCD163 levels have been associated with liver disease severity and progression. During liver transplantation, the implanted liver is exposed to ischaemia and reperfusion injury, resulting in an acute inflammatory response and macrophage activation. The relationship between sCD163 levels during liver transplantation and the development of early allograft dysfunction (EAD) has not been investigated. We included 27 cirrhosis patients (age 55 [range 32–72] years, 23 men) on the waiting list for liver transplantation. Alcohol consumption and viral hepatitis were the most frequent causes for cirrhosis. Patients were characterised by standard biochemical analysis and based on clinical disease severity scores. Information about donor, graft and course of the liver transplantation was recorded. sCD163 levels were measured at the time of liver transplantation before surgery, 2 h after reperfusion, and then at 24 h after transplantation. We observed above-normal sCD163 levels at baseline (5.9 mg/L [4.7–8.8]). Two hours after reperfusion, sCD163 levels increased significantly from baseline (8.4 mg/L [7.4–10.9]; P < 0.01). Twenty-four hours after transplantation, sCD163 levels were significantly reduced compared with baseline (3.7 mg/L [2.9–5.5]; P < 0.01). However, in patients with EAD (n = 16), sCD163 levels were increased compared with patients without EAD (4.1 [3.2–7.4] vs. 3.1 [2.8–3.8] mg/L; P = 0.03). We observed elevated sCD163 levels in patients with EAD after liver transplantation, confirming macrophage activation to play a role in EAD. Thus, sCD163 may be used as an early marker for EAD after liver transplantation, but larger studies are warranted to validate these findings. [ABSTRACT FROM AUTHOR]

Abstract Background Acute Kidney Injury, a common complication of liver transplant, is associated with a significant increase in the risk of morbidity, mortality and graft loss. Current diagnostic criteria leaves a delay in diagnosis allowing further potential irreversible damage. Early biomarkers of renal injury are of clinical importance and Neutrophil Gelatinase Associated Lipocalins (NGALs) and Syndecan-1 were investigated. Methods AKI was defined according to the Acute Kidney Injury Network criteria. Urine and blood samples were collected pre-operatively, immediately post-op and 24 h post reperfusion to allow measurement of NGAL and Syndecan-1 levels. Results 13 of 27 patients developed an AKI. Patients who developed AKI had significantly higher peak transaminases. Urinary NGAL, plasma NGAL and Syndecan-1 levels were significantly elevated in all patients post reperfusion. Urinary NGAL levels immediately post-op were significantly higher in patients who developed an AKI than those that didn't [1319 ng/ml vs 46.56 ng/ml, p ≤ 0.001]. ROC curves were performed and urinary NGAL levels immediately post-op were an excellent biomarker for AKI with an area under the curve of 0.948 (0.847–1.00). Conclusions Urinary NGAL levels measured immediately post-op accurately predict the development of AKI and their incorporation into clinical practise could allow early protocols to be developed to treat post transplant AKI. [ABSTRACT FROM AUTHOR]

Background Ischaemia Reperfusion (IR) injury is a major cause of morbidity, mortality and graft loss following Orthotopic Liver Transplantation (OLT). Utilising marginal grafts, which are more susceptible to IR injury, makes this a key research goal. Remote Ischaemic Preconditioning (RIPC) has been shown to ameliorate hepatic IR injury in experimental models. Whether RIPC can reduce IR injury in human liver transplant recipients is unknown. Methods Forty patients undergoing liver transplantation were randomized to RIPC or a sham. RIPC was induced through three 5 min cycles of alternate ischaemia and reperfusion of the left leg prior to surgery. Data on clinical outcomes was collected prospectively. Per-operative cytokine levels were measured. Results Fourty five of 51 patients approached (88%) were willing to enroll in the study. Five patients were excluded and 40 randomized, of which 20 underwent RIPC which was successfully completed in all patients. There were no complications following RIPC. Median day 3 AST levels were slightly higher in the RIPC group (221 IU vs 149 IU, p = 1.00). Conclusions RIPC is acceptable and safe in liver transplant recipients. This study has not demonstrated evidence of a reduction in short-term measures of IR injury. Longer follow up will be required and consideration of an altered protocol. [ABSTRACT FROM AUTHOR]

Introduction The presence of positive nodal disease ( LND) and the number of lymph nodes involved ( LNB) are known to be significant prognostic markers for resected adenocarcinoma of the pancreas. In addition, the ratio of the number of involved nodes to the number of nodes resected known as the lymph node ratio ( LNR) is emerging as an important prognostic marker. The role of the resection margin ( RM) as presently defined (R1 ≤ 1 mm) is unclear as results differ based on the dataset. The aim of this study was to assess the impact of nodal disease and a redefined RM on outcome. Material and methods Retrospective analysis of pancreatic head resections for adenocarcinomas from 2003-2009. The RM was re-analysed based on tumour clearance and categorized into: histopathological evidence of a tumour; ≤0.5 mm, ≤1 mm, ≤1.5 mm, or ≤2.0 mm of the actual surgical resection margin. The impact of histopathological variables on cancer-specific survival ( CSS) and disease-free survival ( DFS) was analysed. Results LND, LNB and LNR were independent prognostic markers for CSS ( P = 0.048, 0.003, 0.016) but, did not influence DFS. A LNR < 0.143 was associated with a higher CSS [38.16 ± 4.69 versus 20.59 ± 2.20 months, P = 0.0042, hazard ratio ( HR) 3.74 (95% confidence interval ( CI) 1.52-9.23)]. An R1 RM was not associated with CSS or DFS on multivariate analysis, irrespective of the distance. LNB and LNR maintained independent significance irrespective of the size of the RM. Conclusion LNB and LNR are the only prognostic factors for CSS in patients with pancreatic head adenocarcinoma, but do not predict recurrence. Microscopic RMs does not seem to influence the outcome even when redefined. Further prospective studies are indicated to substantiate these findings. [ABSTRACT FROM AUTHOR]

Background: Remote ischaemic preconditioning (RIPC) is a novel method of protecting the liver from ischaemia-reperfusion (I-R) injury. Protective effects in the early phase (4-6 h) have been demonstrated, but no studies have focused on the late phase (24 h) of hepatic I-R. This study analysed events in the late phase of I-R following RIPC and focused on the microcirculation, inflammatory cascade and the role of cytokine-induced neutrophil chemoattractant-1 (CINC-1). Methods: A standard animal model was used. Remote preconditioning prior to I-R was induced by intermittent limb ischaemia. Ischaemia was induced in the left and median lobes of the liver (70%). The animals were recovered after 45 min of liver ischaemia. At 24 h, the animals were re-evaluated under anaesthesia. Hepatic microcirculation, sinusoidal leukocyte adherence and hepatocellular death were assessed by intravital microscopy, hepatocellular injury by standard biochemistry and serum CINC-1 by enzyme-linked immunosorbent assay (ELISA). Results: At 24 h post I-R, RIPC was found to have improved sinusoidal flow by increasing the sinusoidal diameter. There was no effect of preconditioning on the velocity of red blood cells, by contrast with the early phase of hepatic I-R. Remote ischaemic preconditioning significantly reduced hepatocellular injury, neutrophil-induced endothelial injury and serum CINC-1 levels. Conclusions: Remote ischaemic preconditioning is amenable to translation into clinical practice and may improve outcomes in liver resection surgery and transplantation. [ABSTRACT FROM AUTHOR]

Abstract: Background: Mild to moderate steatotic livers are used as marginal donors in liver transplantation. Very little is known about the mechanisms of ischemia reperfusion (IR) injury (IRI) in fatty liver. This study aimed to establish whether cytochrome oxidase C (COX) activity is compromised by IRI in fatty liver and whether ischemic preconditioning (IPC) can protect COX activity. Methods: New Zealand rabbits were fed on a high-cholesterol diet for 8 weeks to induce moderate hepatic steatosis. Three groups were tested. The IR group underwent 60 minutes of ischemia, followed by 7 hours of reperfusion. The IPC group (IPC + IR) underwent 5 minutes of ischemia, followed by 10 minutes of reperfusion and then 60 minutes of ischemia and 7 hours of reperfusion. The control group (sham) underwent the same surgical procedure, but ischemia was not induced. Deoxyhemoglobin, oxyhemoglobin, and change in the redox state of COX was continuously monitored in vivo by near-infrared spectroscopy. COX and citrate synthase (CS) activity assays were carried out on liver biopsy specimens in vitro. Bile was collected continuously during the procedure and analyzed using proton nuclear magnetic resonance spectroscopy. Results: The IR group had decreased COX activity and tissue oxygenation represented by deoxyhemoglobin, oxyhemoglobin, COX, and elevated redox ratios of lactate/pyruvate and β-hydroxybutarate/acetoacetate in vivo and a decrease in COX and CS activity in vitro. The IPC + IR group showed higher levels of all measured parameters in vivo and showed a smaller decrease in COX and CS activity in vitro. Conclusion: This study shows that IRI affects COX activity in fatty livers. This is attenuated by IPC. [Copyright &y& Elsevier]

Background: The use of synthetic analogues of somatostatin following pancreatic surgery is controversial. The aim of this meta-analysis is to determine whether prophylactic somatostatin analogues (SAs) should be used routinely in pancreatic surgery. Methods: Randomized controlled trials were identified from the Cochrane Library Trials Register, MEDLINE, EMBASE, Science Citation Index Expanded and reference lists. Data were extracted from these trials by two independent reviewers. The risk ratio (RR), mean difference (MD) and standardized mean difference (SMD) were calculated with 95% confidence intervals (95% CIs) based on intention-totreat or available case analysis. Results: Seventeen trials involving 2143 patients were identified. The overall number of patients with postoperative complications was lower in the SA group (RR 0.71, 95% CI 0.62-0.82), but there was no difference between the groups in perioperative mortality (RR 1.04, 95% CI 0.68-1.59), re-operation rate (RR 1.15, 95% CI 0.56-2.36) or hospital stay (MD -1.04 days, 95% CI -2.54 to 0.46). The incidence of pancreatic fistula was lower in the SA group (RR 0.64, 95% CI 0.53-0.78). The proportion of these fistulas that were clinically significant is not clear. Analysis of results of trials that clearly distinguished clinically significant fistulas revealed no difference between the two groups (RR 0.69, 95% CI 0.34-1.41). Subgroup analysis revealed a shorter hospital stay in the SA group than among controls for patients with malignant aetiology (MD -7.57 days, 95% CI -11.29 to -3.84). Conclusions: Somatostatin analogues reduce perioperative complications but do not reduce perioperative mortality. However, they do shorten hospital stay in patients undergoing pancreatic surgery for malignancy. Further adequately powered trials of low risk of bias are necessary. [ABSTRACT FROM AUTHOR]

Background: Vascular occlusion during liver resection results in ischaemia-reperfusion (IR) injury, which can lead to liver dysfunction. We performed a systematic review and meta-analysis to assess the benefits and harms of using various pharmacological agents to decrease IR injury during liver resection with vascular occlusion. Methods: Randomized clinical trials (RCTs) evaluating pharmacological agents in liver resections conducted under vascular occlusion were identified. Two independent reviewers extracted data on population characteristics and risk of bias in the trials, and on outcomes such as postoperative morbidity, hospital stay and liver function. Results: A total of 18 RCTs evaluating 17 different pharmacological interventions were identified. There was no significant difference in perioperative mortality, liver failure or postoperative morbidity between the intervention and control groups in any of the comparisons. A significant improvement in liver function was seen with methylprednisolone use. Hospital and intensive therapy unit stay were significantly shortened with trimetazidine and vitamin E use, respectively. Markers of liver parenchymal injury were significantly lower in the methylprednisolone, trimetazidine, dextrose and ulinastatin groups compared with their respective controls (placebo or no intervention). Discussion: Methylprednisolone, trimetazidine, dextrose and ulinastatin may have protective roles against IR injury in liver resection. However, based on the current evidence, they cannot be recommended for routine use and their application should be restricted to RCTs. [ABSTRACT FROM AUTHOR]

Background: Liver transplantation and resection surgery involve a period of ischaemia and reperfusion to the liver which initiates an inflammatory cascade resulting in liver and remote organ injury. Bucillamine is a low-molecular-weight thiol antioxidant that is capable of rapidly entering cells. Methods: The effect of bucillamine was studied in a rat model of liver ischaemia--reperfusion injury with 45 min of partial (70%) liver ischaemia and at 3 and 24 h of reperfusion. Controls included ischaemia-reperfusion (I/R) only, sham and bucillamine alone (without ischaemia reperfusion). Liver injury was assessed by serum transaminases (AST and ALT). Sinusoidal blood flow and hepatocyte apoptosis were measured using intravital microscopy (IVM). Results: The hepatocellular injury of I/R produced a markedly elevated serum AST which was reduced with bucillamine (2072.5 ± 511.79 vs. 932 ± 200.8, P < 0.05) at 3 h reperfusion. Bucillamine treatment with I/R also increased parenchymal blood flow [red blood cell (RBC) velocity 242.66 ± 16.86 vs. 181.11 ± 17.59, at the end of 3 h of reperfusion) and reduced hepatocyte necrosis/apoptosis at 3 h as well as 24 h (P > 0.001). Conclusion: Bucillamine reduces the hepatocellular injury of liver ischaemia reperfusion and improves parenchymal perfusion. [ABSTRACT FROM AUTHOR]

Background: Liver transplantation involves a period of ischemia and reperfusion to the graft which leads to primary non-function and dysfunction of the liver in 5-10% of cases. Remote ischemic preconditioning (RIPC) has been shown to reduce ischemia reperfusion injury (IRI) injury to the liver and increase hepatic blood flow. We hypothesized that RIPC may directly modulate hepatic microcirculation and have investigated this using intravital microscopy. Methods: A rat model of liver IRI was used with 45 min of partial hepatic ischemia (70%) followed by 3 h of reperfusion. Four groups of animals (Sham, IRI, RIPC+IRI, RIPC+Sham) were studied (n = 6, each group). Intravital microscopy was used to measure red blood cell (RBC) velocity, sinusoidal perfusion, sinusoidal flow and sinusoidal diameter. Neutrophil adhesion was assessed by rhodamine labeling of neutrophils and cell death using propidium iodide. Results: RIPC reduced the effects of IRI by significantly increasing red blood cell velocity, sinusoidal flow and sinusoidal perfusion along with decreased neutrophil adhesion and cell death. Conclusions: Using intravital microscopy, this study demonstrates that RIPC modulates hepatic microcirculation to reduce the effects of IRI. HO-1 may have a key role in the modulation of hepatic microcirculation and endothelial function. [ABSTRACT FROM AUTHOR]

Abstract: Plasma S-nitrosothiols (RSNOs) may act as a circulating form of nitric oxide that affects vascular function and platelet aggregation. Their role in liver ischemia/reperfusion (I/R) injury is largely unknown. The aim of the present study was to investigate the changes in plasma RSNOs following liver I/R injury. Two groups of New Zealand white rabbits were used (n=6, each): the I/R group underwent 60 min lobar liver ischemia and 7 h reperfusion, while the sham group underwent laparotomy but no liver ischemia. Serial RSNO levels were measured in plasma by electron paramagnetic resonance (EPR) spectrometry, nitrite/nitrates by capillary electrophoresis, hepatic microcirculation by laser Doppler flowmetry, redox state of hepatic cytochrome oxidase by near-infrared spectroscopy, liver iNOS mRNA expression by reverse transcription-polymerase chain reaction (RT-PCR) and the oxidation of dihydrorhodamine to rhodamine by fluorescence. The effect of the antioxidant N-acetylcysteine (NAC) on RSNOs formation and DHR oxidation was tested in a third group of animals (n=6) undergoing lobar liver I/R. Hepatic I/R was associated with a significant increase in plasma RSNOs, plasma nitrites, hepatic iNOS mRNA expression, impairment in hepatic microcirculation, decrease in the redox state of cytochrome oxidase, and significant production of rhodamine. The changes were more obvious during the late phase of reperfusion (>4 h). NAC administration decreased plasma RSNOs and oxidation of DHR to RH (P<0.05, 5 and 7 h postreperfusion, respectively). These results suggest that significant upregulation of nitric oxide synthesis during the late phase of reperfusion is associated with impairment in microcirculation and mitochondrial dysfunction. Plasma S-nitrosothiols are a good marker of this nitric oxide-mediated hepatotoxicity. [Copyright &y& Elsevier]