Adam Bartlett

Additive effect of pretransplant obesity, diabetes, and cardiovascular risk factors on outcomes after liver transplantation

The effects of pretransplant obesity, diabetes mellitus (DM), coronary artery disease (CAD), and hypertension (HTN) on outcomes after liver transplantation (LT) are controversial. Questions have also been raised about the appropriateness of the body mass index (BMI) for assessing obesity in patients with end‐stage liver disease. Both issues have implications for organ allocation in LT. To address these questions, we undertook a cohort study of 202 consecutive patients (2000‐2010) undergoing LT at a national center in New Zealand. BMI and body fat percentage (%BF) values (dual‐energy X‐ray absorptiometry) were measured before transplantation, and the methods were compared. The influence of pretransplant risk variables (including obesity, DM, CAD, and HTN) on the 30‐day postoperative event rate, length of hospital stay, and survival were analyzed. There was agreement between the calculated BMI and the measured %BF for 86.0% of the study population (κ coefficient = 0.73, 95% confidence interval = 0.61‐0.85), and this was maintained across increasing Model for End‐Stage Liver Disease scores. Obesity was an independent risk factor for the postoperative event rate [count ratio (CR) = 1.03, P < 0.001], as was DM (CR = 1.4, P < 0.001). Obesity with concomitant DM was the strongest predictor of the postoperative event rate (CR = 1.75, P < 0.001) and a longer hospital stay (5.81 days, P < 0.01). Independent metabolic risk factors had no effect on 30‐day, 1‐year, or 5‐year patient survival. In conclusion, BMI is an adequate tool for assessing obesity‐associated risk in LT. Early post‐LT morbidity is highest for patients with concomitant obesity and DM, although these factors do not appear to influence recipient survival. Liver Transpl 20:281‐290, 2014.

Pancreatic Trauma-12-year Experience From a Tertiary Center

Pancreatic trauma is rare and often missed during initial assessment of patients with abdominal trauma. This study reviews our experience of managing pancreatic trauma at a tertiary referral center and discusses the diagnostic and therapeutic challenges. Methods: A retrospective study of our prospectively maintained hepato-pancreatico-biliary database for 12 years preceding December 2007. Results: Twenty-eight patients (23 males, 10 children) with a median age of 11.5 years (range, 6-16 years) in children and 27.5 years (range, 17-54 years) in adults were identified. Nineteen of the 28 had pancreatic duct injury of which 15 were missed on initial evaluation and referred after conservative management (n = 9) or laparotomy (n = 6). Twenty-one patients developed complications including abdominal collections (n = 10), pancreatic fistulae (n = 9), and pseudocysts (n = 2). There were 2 deaths (7%), both of which were associated with multiple intra-abdominal injuries. At a median follow-up of 7.5 months (range, 3-44 months), 19 of 23 patients were asymptomatic and had been discharged from follow-up. Conclusions: Pancreatic trauma in the United Kingdom is mainly the result of blunt trauma and most commonly affects young males. The presence of pancreatic duct disruption accounts for most of the complications, and in the absence of associated injuries, mortality is rare.

Cusum analysis of trends in operative selection and conversion rates for laparoscopic cholecystectomy

Background: Laparoscopic cholecystectomy (LC) requires a high degree of technical ability, spatial resolution and dexterity. Assessing trainees and competent operators is an important aspect of quality assurance in patient care. Most institutions quote mean conversion rate as a method of comparing operators’ performance. The purpose of the present study was to use the technique of cumulative sum (cusum) analysis to determine whether a learning curve phenomenon exists in operators performing LC.

The Impact of Hepatic Steatosis on Hepatic Ischemia-Reperfusion Injury in Experimental Studies: A Systematic Review

Background. The impact of hepatic steatosis on outcome following hepatic ischemia-reperfusion injury (IRI) remains controversial with conflicting clinical results. A number of experimental studies have been published examining the relationship between hepatic steatosis and IRI. This systematic review evaluates these experimental studies. Methods. An electronic search of the Medline and Embase databases (January 1946 to June 2012) was performed to identify studies that reported relevant outcomes in animal models of hepatic steatosis subjected to IRI. Results. A total of 1314 articles were identified, of which 33 met the predefined criteria and were included in the study. There was large variation in the type of animal model, duration, and type of IRI and reporting of histological findings. Increased macrovesicular steatosis (>30%) was associated with increased histological damage, liver function derangement, and reduced survival. Increased duration of warm or cold ischemia had a negative impact on all outcomes measured. Microvesicular steatosis did not influence outcome. Conclusions. Findings from this systemic review support the hypothesis that livers with >30% macrovesicular steatosis are less tolerant of IRI. Clinically, it is likely that these findings are applicable to patients undergoing hepatic resection, but further studies are required to confirm these data.

The immunophenotype of antigen presenting cells of the mononuclear phagocyte system in normal human liver - A systematic review

The mononuclear phagocytic system (MPS), comprised of monocytes, macrophages, and dendritic cells, is essential in tissue homeostasis and in determining the balance of the immune response through its role in antigen presentation. It has been identified as a therapeutic target in infectious disease, cancer, autoimmune disease and transplant rejection. Here, we review the current understanding of the immunophenotype and function of the MPS in normal human liver. Using well-defined selection criteria, a search of MEDLINE and EMBASE databases identified 76 appropriate studies. The majority (n=67) described Kupffer cells (KCs), although the definition of KC differs between sources, and little data were available regarding their function. Only 10 papers looked at liver dendritic cells (DCs), and largely confirmed the presence of the major dendritic cell subsets identified in human blood. Monocytes were thoroughly characterized in four studies that utilized flow cytometry and fluorescent microscopy and highlighted their prominent role in liver homeostasis and displayed subtle differences from circulating monocytes. There was some limited evidence that liver DCs are tolerogenic but neither liver dendritic cell subsets nor macrophages have been thoroughly characterized, using either multi-colour flow cytometry or multi-parameter fluorescence microscopy. The lobular distribution of different subsets of liver MPS cells was also poorly described, and the ability to distinguish between passenger leukocytes and tissue resident cells remains limited. It was apparent that further research, using modern immunological techniques, is now required to accurately characterize the cells of the MPS in human liver.

SIRveNIB: Selective Internal Radiation Therapy Versus Sorafenib in Asia-Pacific Patients With Hepatocellular Carcinoma

Purpose Selective internal radiation therapy or radioembolization (RE) shows efficacy in unresectable hepatocellular carcinoma (HCC) limited to the liver. This study compared the safety and efficacy of RE and sorafenib in patients with locally advanced HCC. Patients and Methods SIRveNIB (selective internal radiation therapy v sorafenib), an open-label, investigator-initiated, phase III trial, compared yttrium-90 (90Y) resin microspheres RE with sorafenib 800 mg/d in patients with locally advanced HCC in a two-tailed study designed for superiority/detriment. Patients were randomly assigned 1:1 and stratified by center and presence of portal vein thrombosis. Primary end point was overall survival (OS). Efficacy analyses were performed in the intention-to-treat population and safety analyses in the treated population. Results A total of 360 patients were randomly assigned (RE, 182; sorafenib, 178) from 11 countries in the Asia-Pacific region. In the RE and sorafenib groups, 28.6% and 9.0%, respectively, failed to receive assigned therapy without significant cross-over to either group. Median OS was 8.8 and 10.0 months with RE and sorafenib, respectively (hazard ratio, 1.1; 95% CI, 0.9 to 1.4; P = .36). A total of 1,468 treatment-emergent adverse events (AEs) were reported (RE, 437; sorafenib, 1,031). Significantly fewer patients in the RE than sorafenib group had grade ≥ 3 AEs (36 of 130 [27.7%]) v 82 of 162 [50.6%]; P < .001). The most common grade ≥ 3 AEs were ascites (five of 130 [3.8%] v four of 162 [2.5%] patients), abdominal pain (three [2.3%] v two [1.2%] patients), anemia (zero v four [2.5%] patients), and radiation hepatitis (two [1.5%] v zero [0%] patients). Fewer patients in the RE group (27 of 130 [20.8%]) than in the sorafenib group (57 of 162 [35.2%]) had serious AEs. Conclusion In patients with locally advanced HCC, OS did not differ significantly between RE and sorafenib. The improved toxicity profile of RE may inform treatment choice in selected patients.

Modeling the hepatic arterial buffer response in the liver

In this paper we present an electrical analog model for the hepatic arterial buffer response (HABR), an intrinsic regulation mechanism in the liver whereby the arterial flow counteracts the changes in portal venous flow. The model itself is a substantial simplification of a previously published model, with nonlinear arterial and portal resistors introduced to account for the dynamic HABR effects. We calibrate the baseline model using published hemodynamic data, and then perform a virtual portal occlusion simulation where the portal vein is half or fully occluded. The simulation results, which suggest that the increased arterial flow cannot fully compensate lost portal perfusion, are consistent with clinical reports and animal model findings. Since HABR functions in both the whole liver and liver graft after transplantation, we also simulate blood flow in a virtual right-lobe graft by adjusting the electronic component parameters in the electric circuit, and our model is able to reproduce the portal venous hyperperfusion and hepatic arterial hypoperfusion conditions due to the HABR effects.

Critical Care of the Potential Organ Donor

Organ transplantation represents one of the great success stories of 20th century medicine. However, its continued success is greatly limited by the shortage of donor organs. This has led to an increased focus within the critical care community on optimal identification and management of the potential organ donor. The multi-organ donor can represent one of the most complex intensive care patients, with numerous competing physiological priorities. However, appropriate management of the donor not only increases the number of organs that can be successfully donated but has long-term implications for the outcomes of multiple recipients. This review outlines current understandings of the physiological derangements seen in the organ donor and evaluates the available evidence for management strategies designed to optimize donation potential and organ recovery. Finally, emerging management strategies for the potential donor are discussed within the current ethical and legal frameworks permitting donation after both brain and circulatory death.

Analysis of Intragraft Gene and Protein Expression of the Costimulatory Molecules, CD80, CD86 and CD154, in Orthotopic Liver Transplant Recipients

CD40‐CD154 and/or CD28‐CD80/86 costimulatory blockade induces long‐term allograft survival in numerous animal models. Studies examining the expression of costimulatory molecules during acute cellular rejection (ACR) have been limited to renal and cardiac allografts.

Meta-analysis of antecolic versus retrocolic gastric reconstruction after a pylorus-preserving pancreatoduodenectomy

INTRODUCTION Delayed gastric emptying (DGE) is a common complication after a pylorus-preserving pancreatoduodenectomy (PPPD) and is associated with significant morbidity. This study determines whether DGE is affected by antecolic (AC) or retrocolic (RC) reconstruction after a PPPD. METHOD An electronic search was performed of the MEDLINE, EMBASE and PubMed databases to identify all articles related to this topic. Pooled risk ratios (RR) were calculated for categorical outcomes, and mean differences (MD) for secondary continuous outcomes using the fixed-effects and random-effects models for meta-analysis. RESULTS Nine studies including 878 patients met the inclusion criteria. DGE was lower with an AC reconstruction RR 0.31 [0.12, 0.78] Z = 2.47 (P = 0.010). Length of stay (LOS) MD -4 days [-7.63, -1.14] Z = 2.65 (P = 0.008) and days to commence a solid diet MD -5 days [-6.63, -3.15] Z = 5.50 (P ≤ 0.000) were also significantly in favour of the AC group. There was no difference in the incidence of pancreatic fistula, intra-abdominal collection/bile leak or mortality between the two groups. CONCLUSION AC reconstruction after PPPD is associated with a lower incidence of DGE. Time to oral intake was significantly shorter with AC reconstruction, with a reduced hospital stay.