Biliary complications in pediatric liver transplantation: Incidence and management over a decade.

This study analyzed how features of a liver graft and the technique of biliary reconstruction interact to affect biliary complications in pediatric liver transplantation. A retrospective analysis was performed of data collected from 2001 to 2011 in a single high-volume North American pediatric transplant center. The study cohort comprised 173 pediatric recipients, 75 living donor (LD) and 98 deceased donor (DD) recipients. The median follow-up was 70 months. Twenty-nine (16.7%) patients suffered a biliary complication. The majority of leaks (9/12, 75.0%) and the majority of strictures (18/22, 81.8%) were anastomotic. There was no difference in the rate of biliary complications associated with DD (18.4%) and LD (14.7%) grafts (P = 0.55). Roux-en-Y (RY) reconstruction was associated with a significantly lower rate of biliary complications compared to duct-to-duct reconstruction (13.3% versus 28.2%, respectively; P = 0.048). RY anastomosis was the only significant factor protecting from biliary complications in our population (hazard ratio, 0.30; 95% confidence interval, 0.1-0.85). The leaks were managed primarily by relaparotomy (10/12, 83.3%), and the majority of strictures were managed by percutaneous biliary intervention (14/22, 63.6%). Patients suffering biliary complications had inferior graft survival (P = 0.04) at 1, 5, and 10 years compared to patients without biliary complications. Our analysis demonstrates a lower incidence of biliary complications with RY biliary reconstruction, and patients with biliary complications have decreased graft survival.

Thrombolytic protocol minimizes ischemic-type biliary complications in liver transplantation from donation after circulatory death donors.

Liver transplantation (LT) with donation after circulatory death (DCD) donors has been associated with a high rate of ischemic-type biliary strictures (ITBSs) and inferior graft survival. To investigate the impact of an intraoperative tissue plasminogen activator (tPA) on outcomes following DCD LT, we conducted a retrospective analysis of DCD LT at the Toronto General Hospital (TGH) and the Ochsner Medical Center (OMC). Between 2009 and 2013, 85 DCD LTs were performed with an intraoperative tPA injection (n = 30 at TGH, n = 55 at OMC), and they were compared with 33 DCD LTs without a tPA. Donor and recipient characteristics were similar in the 2 groups. There was no significant difference in the intraoperative packed red blood cell transfusion requirement (3.2 ± 3.4 versus 3.1 ± 2.3 U, P = 0.74). Overall, biliary strictures occurred less commonly in the tPA-treated group (16.5% versus 33.3%, P = 0.07) with a much lower rate of diffuse intrahepatic strictures (3.5% versus 21.2%, P = 0.005). After 1 and 3 years, the tPA group versus the non-tPA group had superior patient survival (97.6% versus 87.0% and 92.7% versus 79.7%, P = 0.016) and graft survival (96.4% versus 69.7% and 90.2% versus 63.6%, P < 0.001). In conclusion, a tPA injection into the hepatic artery during DCD LT reduces ITBSs and improves graft and patient survival without increasing the risk for bleeding.

A catheter-based suture-free approach to bilioenteric anastomosis: a pilot study.

Bilioenteric anastomoses are commonly performed during liver transplantation, reconstruction following tumor resection, and repair of bile duct injury. Ischemia plays an important role in both short- and long-term complications related to biliary anastomoses. The authors describe a catheter-based, suture-free approach to bilioenteric anastomosis that aims to reduce or eliminate tissue trauma and foreign material that contribute to anastomotic ischemia. The device uses a novel "umbrella" anchoring mechanism to approximate bowel to the transected bile duct over a percutaneously placed transhepatic catheter. The authors performed an open choledochojejunostomy using the device in 7 pigs. The anastomosis was assessed with cholangiography, gross inspection, and histology at the time of necropsy. The procedure was well tolerated, with no evidence of anastomotic leak in any of the study animals. This alternative catheter-based approach to bilioenteric anastomoses is safe and effective, offers potential advantages over traditional approaches, and can be easily adapted to a minimal access surgery.

The human microbiome and surgical disease.

OBJECTIVE: The purpose of this review article is to summarize what is currently known about microbes associated with the human body and to provide examples of how this knowledge impacts the care of surgical patients. BACKGROUND: Pioneering research over the past decade has demonstrated that human beings live in close, constant contact with dynamic communities of microbial organisms. This new reality has wide-ranging implications for the care of surgical patients. METHODS AND RESULTS: Recent advances in the culture-independent study of the human microbiome are reviewed. To illustrate the translational relevance of these studies to surgical disease, we discuss in detail what is known about the role of microbes in the pathogenesis of obesity, gastrointestinal malignancies, Crohn disease, and perioperative complications including surgical site infections and sepsis. The topics of mechanical bowel preparation and perioperative antibiotics are also discussed. CONCLUSIONS: Heightened understanding of the microbiome in coming years will likely offer opportunities to refine the prevention and treatment of a wide variety of surgical conditions.

Agent-based dynamic knowledge representation of Pseudomonas aeruginosa virulence activation in the stressed gut: Towards characterizing host-pathogen interactions in gut-derived sepsis.

BACKGROUND: There is a growing realization that alterations in host-pathogen interactions (HPI) can generate disease phenotypes without pathogen invasion. The gut represents a prime region where such HPI can arise and manifest. Under normal conditions intestinal microbial communities maintain a stable, mutually beneficial ecosystem. However, host stress can lead to changes in environmental conditions that shift the nature of the host-microbe dialogue, resulting in escalation of virulence expression, immune activation and ultimately systemic disease. Effective modulation of these dynamics requires the ability to characterize the complexity of the HPI, and dynamic computational modeling can aid in this task. Agent-based modeling is a computational method that is suited to representing spatially diverse, dynamical systems. We propose that dynamic knowledge representation of gut HPI with agent-based modeling will aid in the investigation of the pathogenesis of gut-derived sepsis. METHODOLOGY/PRINCIPAL FINDINGS: An agent-based model (ABM) of virulence regulation in Pseudomonas aeruginosa was developed by translating bacterial and host cell sense-and-response mechanisms into behavioral rules for computational agents and integrated into a virtual environment representing the host-microbe interface in the gut. The resulting gut milieu ABM (GMABM) was used to: 1) investigate a potential clinically relevant laboratory experimental condition not yet developed--i.e. non-lethal transient segmental intestinal ischemia, 2) examine the sufficiency of existing hypotheses to explain experimental data--i.e. lethality in a model of major surgical insult and stress, and 3) produce behavior to potentially guide future experimental design--i.e. suggested sample points for a potential laboratory model of non-lethal transient intestinal ischemia. Furthermore, hypotheses were generated to explain certain discrepancies between the behaviors of the GMABM and biological experiments, and new investigatory avenues proposed to test those hypotheses. CONCLUSIONS/SIGNIFICANCE: Agent-based modeling can account for the spatio-temporal dynamics of an HPI, and, even when carried out with a relatively high degree of abstraction, can be useful in the investigation of system-level consequences of putative mechanisms operating at the individual agent level. We suggest that an integrated and iterative heuristic relationship between computational modeling and more traditional laboratory and clinical investigations, with a focus on identifying useful and sufficient degrees of abstraction, will enhance the efficiency and translational productivity of biomedical research.

Balloon-Occlusion Technique for Managing Portal Vein Hemorrhage in Liver Transplantation.

BACKGROUND: Portal vein thrombosis (PVT) is relatively common among candidates for liver transplantation and can present significant intraoperative challenges. Depending on the extent of PVT, thromboendovenectomy (TEV), portal bypass, or systemic inflow may be required to restore portal inflow. While TEV is the most commonly used approach to restore anatomic portal inflow, portal vein injury and life-threatening hemorrhage are risks with this technique. CASE REPORT: We present a salvage technique for managing portal vein injury during TEV using intraluminal balloon occlusion of the portal vein during portal vein repair and reconstruction. This alternative mode of bleeding control optimizes exposure to the retropancreatic space and avoids direct application of vascular clamps that can cause further injury to the vessel and surrounding tissue. CONCLUSION: Careful preoperative planning and anticipation of potential problems are essential for safe and effective management of complex PVT intraoperatively. The balloon-occlusion technique can facilitate safe and efficient repair of a portal vein injury during TEV for liver transplantation.

New variability in cerebrovascular anatomy determines severity of hippocampal injury following forebrain ischemia in the Mongolian gerbil.

Transient bilateral carotid artery occlusion in the Mongolian gerbil is a widely used model of forebrain ischemia due to species-specific absence of communicating arteries between the middle and posterior cerebral arteries. We have found that transient carotid occlusion induces a wide variation in histological injury of the hippocampus, suggesting that Mongolian gerbils currently available in the US have anomalous connections between the vertebral and carotid circulations. We subjected Mongolian gerbils from Harlan Sprague-Dawley and Charles River Laboratories to 5 min of bilateral carotid occlusion under continuous striatal temperature control and assessed hippocampal injury histologically 5 or 14 days later. The severity of occlusion-induced hippocampal injury depended on the presence and size of posterior cerebral communicating arteries. Injury was markedly attenuated in hippocampi having ipsilateral communicating arteries >50 microm in diameter. In contrast, severe ischemic injury occurred when either no posterior communicating artery was present, or when communicating arteries were smaller than 50 microm in diameter. Ischemic injury was independent of any communicating arteries on the contralateral side. Communicating arteries were present in 90% of gerbils from each vendor, ranging from 19 microm to 125 microm in diameter. The high prevalence of posterior communicating arteries and their profound effect on attenuating hippocampal injury indicates that an understanding of the presence and size of posterior communicating cerebral arteries in each animal is now required to interpret the extent of hippocampal injury following bilateral carotid artery occlusion in this species.

Optimizing pancreas transplantation outcomes in obese recipients.

BACKGROUND: Pancreas transplant recipient obesity has been associated with increased risk of perioperative complications, graft failure, and death. The imperative to maximize organ utility must be balanced against the need to maintain equity of access, including for the increasing number of obese diabetic patients. METHODS: We compared the outcomes of pancreas transplant recipients with body mass index (BMI) greater than 30 kg/m(2) (n=60, mean ± SD BMI 32.1 ± 1.7 kg/m(2)) to those with BMI less than 30 kg/m(2) (n=308, mean ± SD BMI 24.5 ± 2.7 kg/m(2)) between 1996 and 2013. RESULTS: There were no differences in the pretransplant recipient or donor characteristics apart from BMI. The BMI greater than 30 group were more likely to suffer a rejection episode (43% vs. 29%; P = 0.03). The median time to first rejection was shorter (1 vs. 6 months; P = 0.04), and wound infection was more common in the BMI greater than 30 group (P = 0.03). There was no difference in the rate of patient, pancreas, or kidney graft survival or difference in graft function between the two groups. CONCLUSION: The obese recipients in this study were in the lower range of the obese category. Although there was an increased risk of rejection and wound infection in the obese group, there was no difference in patient or graft survival. This finding, when compared with previous reports, may be related to stringent recipient selection and posttransplant care particularly with respect to cardiovascular disease.

Antimicrobial resistance in Staphylococcus aureus at the University of Chicago Hospitals: a 15-year longitudinal assessment in a large university-based hospital.

OBJECTIVES: To describe a longitudinal profile of resistance to beta-lactam antimicrobials among isolates of Staphylococcus aureus at a large university teaching hospital and to evaluate the impact of the methicillin resistance phenotype on resistance trends for non-beta-lactam antimicrobials. DESIGN: Retrospective evaluation of antimicrobial susceptibility data for all 17,287 S. aureus isolates obtained from January 1986 through December 2000. SETTING: The University of Chicago Hospitals, a family of tertiary-care, university-affiliated hospitals in Chicago, Illinois, consisting of 547 adult and pediatric beds. RESULTS: The annual rate of resistance to methicillin increased from 13% in 1986 to 28% in 2000 (P < .001) and has not plateaued. For each non-beta-lactam antimicrobial tested, the annual rates of resistance were far higher among methicillin-resistant S. aureus (MRSA) isolates than among methicillin-susceptible S. aureus (MSSA) isolates. The annual rates of resistance to the macrolide, lincosamide, and streptogramin (MLS) antimicrobials erythromycin and clindamycin increased among MSSA isolates (P < .01), but remained lower than 20%. Resistance to the MLS antimicrobials was higher among MRSA isolates (higher than 60%), but the annual rate decreased significantly during the study (P < .01). CONCLUSION: The prevalence of methicillin resistance among S. aureus isolates has continued to increase; resistance to non-beta-lactam antimicrobials is far more common among MRSA isolates. Recent decreases in the proportion of MRSA isolates resistant to non-beta-lactam antimicrobials suggest important changes in the epidemiology of this pathogen.

Vascular dysfunction in ischemia-reperfusion injury.

Microvascular dysfunction mediates many of the local and systemic consequences of ischemic-reperfusion (I/R) injury, with a spectrum of changes specific to arterioles, capillaries, and venules. This review discusses the specific changes in the endothelium during I/R injury; describes the differential responses of the various levels of the vasculature including arterioles, capillaries, and venules; and explores mechanisms for remote organ injury. Vascular dysfunction is largely a consequence of changes in the endothelial cells themselves, affecting the integrity of barrier function, cytokine and adhesion molecule expression, and vascular tone. The bioavailability of nitric oxide, an important mediator of vasodilation, is profoundly decreased during the reperfusion period, resulting in impaired vasodilation of arterioles. Release of inflammatory mediators and increased expression of adhesion molecules initiate inflammatory and coagulation cascades that culminate in the occlusion of capillaries, known as the "no-reflow''" phenomenon. In postcapillary venules, the recruitment and transmigration of leukocytes further compromise the integrity of the endothelial barrier and increase the oxidative burden, resulting in leakage and tissue edema. I/R injury can have significant and untoward consequences beyond the affected tissue, with such conditions as systemic inflammatory response syndrome. This review highlights recent progress in understanding of the varied phenomena of vascular dysfunction in I/R injury and some promising advances in the understanding and application of ischemic preconditioning and other potential therapies.

Physician knowledge of catch-up regimens and contraindications for childhood immunizations.

OBJECTIVES: To determine physician success at designing catch-up regimens for children delayed in immunizations and physician knowledge regarding contraindications to immunization. METHODS: A self-administered survey was completed by pediatricians, general practitioners, and family practitioners in Cook County, Illinois. Surveys included 6 open-ended vignettes describing hypothetical children delayed in immunization for whom participants were asked to design catch-up regimens. Bivariate and multivariate logistic regression were used to determine predictors of correct response. The surveys also inquired about management of scenarios that might be perceived as contraindications to immunize with the Haemophilus influenzae type b or measles-mumps-rubella vaccines. RESULTS: The mean score of correct responses was 1.83 of a possible 6.0. Almost one third of respondents answered all 6 vignettes incorrectly. The proportion of incorrect responses was high for all 6 vignettes (39%-86%), but higher for questions that addressed the immunization of children older than 12 months. Errors in vaccine administration were most commonly attributed to omitted vaccines, with varicella-zoster vaccine and pneumococcal conjugate vaccine omitted most frequently. Pediatricians were >4 times more likely to answer correctly than were family practitioners. Participants in the Vaccines for Children (VFC) program were more than twice as likely to answer correctly than were non-VFC providers. Knowledge of contraindications was inconsistent, particularly for measles-mumps-rubella vaccine. CONCLUSIONS: Childhood vaccine providers have substantial knowledge deficits of recommended immunization schedules and vaccine contraindications that may contribute to missed opportunities to immunize. Pediatricians and participants in the VFC program were more successful at designing catch-up regimens for children with immunization delay.