Quick and simple; psoas density measurement is an independent predictor of anastomotic leak and other complications after colorectal resection.

BACKGROUND: Radiologically defined sarcopenia has been shown to predict negative outcomes after cancer surgery, however radiological assessment of sarcopenia often requires additional software and standardisation against anthropomorphic data. Measuring psoas density using hospital Picture Archiving and Communication Systems (PACS), universally available in the UK, may have advantages over methods requiring the use of additional specialist and often costly software. The aim of this study was to assess the association between radiologically defined sarcopenia measured by psoas density and postoperative outcome in patients having a colorectal cancer resection. METHODS: All patients having a resection for colorectal cancer, discussed by the colorectal multi-disciplinary team in one institution between 1/1/15 and 31/12/15, were retrospectively identified. Mean psoas density at the level of the L3 vertebra was analysed from preoperative computed tomography (CT) scans to define sarcopenia using the Picture Archiving and Communication Systems (PACS). Postoperative complications and mortality were recorded. RESULTS: One hundred and sixty-nine patients had a colorectal resection for cancer and 140 of these had a primary anastomosis. Ninety-day mortality and 1-year mortality were 1.1% and 7.1%, respectively. Eighteen (10.7%) patients suffered a Clavien-Dindo grade 3 or 4 complication of which 6 (33%) were anastomotic leaks. In the whole cohort, sarcopenia was associated with an increased risk of Clavien-Dindo grade 3 or 4 complications [adjusted OR 6.33 (1.65-24.23) p = 0.007]. In those who had an anastomosis, sarcopenia was associated with an increased risk of anastomotic leak [adjusted OR 14.37 (1.37-150.04) p = 0.026]. CONCLUSIONS: A quick and easy radiological assessment of sarcopenia by measuring psoas density on preoperative CT scan using software universally available in the UK is highly predictive of postoperative morbidity in colorectal cancer patients.

The use of a novel adhesive tissue patch as an aid to anastomotic healing.

Introduction One of the most feared complications of colorectal surgery is anastomotic leak. Numerous techniques have been studied in the hope of decreasing leakage. This study was designed to assess the handling characteristics of a novel adhesive tissue patch (TissuePatch™; Tissuemed, Leeds, UK) applied to colorectal anastomoses in a pilot study. This was with a view to assessing its potential role in aiding anastomotic healing in subsequent trials. Methods A patch was applied to colorectal anastomoses after the surgeon had completed the anastomosis and prior to abdominal closure. Handling characteristics and patient outcomes were recorded prospectively. Results Nine patients were recruited before the study was prematurely terminated. In one patient, the patch fell off and in another patient, the surgeon omitted to apply it. Six patients had significant postoperative problems (1 confirmed leak necessitating return to theatre and excision anastomosis, 3 suspicious of leak on computed tomography delaying discharge, 2 perianastomotic collections). One patient had an uneventful recovery. Conclusions Although the handling characteristics of this novel tissue patch were deemed satisfactory, it appears that wrapping a colorectal anastomosis with an adhesive hydrophilic patch has significant deleterious effects on anastomotic healing. This could be a consequence of the creation of a microenvironment between the patch and the anastomosis that impairs healing. Further research is required to better understand the mechanisms involved. At present, the use of such patches on colorectal anastomoses should be discouraged outside the confines of a well monitored trial.

The American Society of Transplantation Consensus Conference on the Use of Hepatitis C Viremic Donors in Solid Organ Transplantation.

The availability of direct-acting antiviral agents for the treatment of hepatitis C virus (HCV) infection has resulted in a profound shift in the approach to the management of this infection. These changes have affected the practice of solid organ transplantation by altering the framework by which patients with end-stage organ disease are managed and receive organ transplants. The high level of safety and efficacy of these medications in patients with chronic HCV infection provides the opportunity to explore their use in the setting of transplanting organs from HCV-viremic patients into non-HCV-viremic recipients. Because these organs are frequently discarded and typically come from younger donors, this approach has the potential to save lives on the solid organ transplant waitlist. Therefore, an urgent need exists for prospective research protocols that study the risk versus benefit of using organs for hepatitis C-infected donors. In response to this rapidly changing practice and the need for scientific study and consensus, the American Society of Transplantation convened a meeting of experts to review current data and develop the framework for the study of using HCV viremic organs in solid organ transplantation.

The Living Donor Collective: A Scientific Registry for Living Donors.

In the setting of an overall decline in living organ donation and new questions about long-term safety, a better understanding of outcomes after living donation has become imperative. Adequate information on outcomes important to donors may take many years to ascertain and may be evident only by comparing large numbers of donors with suitable controls. Previous studies have been unable to fully answer critical questions, primarily due to lack of appropriate controls, inadequate sample size, and/or follow-up duration that is too short to allow detection of important risks attributable to donation. The Organ Procurement and Transplantation Network does not follow donors long term and has no prospective control group with which to compare postdonation outcomes. There is a need to establish a national living donor registry and to prospectively follow donors over their lifetimes. In addition, there is a need to better understand the reasons many potential donors who volunteer to donate do not donate and whether the reasons are justified. Therefore, the US Health Resources and Services Administration asked the Scientific Registry of Transplant Recipients to establish a national registry to address these important questions. Here, we discuss the efforts, challenges, and opportunities inherent in establishing the Living Donor Collective.

Non-centralised service for palliative stenting of malignant gastric outlet obstruction.

INTRODUCTION: Malignant gastric outlet obstruction (GOO) is a common, debilitating and frequently pre-terminal symptom of intra-abdominal malignancies. Traditional 'gold standard' treatment has been palliative surgical gastro-enterostomy. Over the past two decades, use of self-expanding metallic stents (SEMSs) to relieve malignant GOO has become first-line treatment. We present the results from a single district general hospital in the UK in which malignant GOO was treated with SEMSs over a six-year period. METHODS: All patients who underwent palliative stenting for malignant gastro-duodenal tumours in our centre for six years up to January 2013 were assessed retrospectively. Outcomes were assessed with regard to: technical and clinical success; return to oral nutrition; prevalence of complications and re-intervention; and overall survival. RESULTS: Thirty-two stents were implanted in 29 patients. Technical success was 100%. Clinical success and return to oral nutrition were both 91%. The prevalence of complications was 16%. The prevalence of re-intervention was 13%. Mean survival was 91 (range, 5-392) days. Median wait from decision to implant a stent to stent implantation was 1 (range, 0-14) day. Overall, 25 covered and nine uncovered stents were implanted. CONCLUSION: Stent implantation for GOO in this patient group is an established and preferable alternative to surgical intervention. Much of the treatment for malignancies of the upper gastrointestinal tract has now been centralised. Our data showed comparable results with published data for these procedures, with a high prevalence of success and low prevalence of major complications. It is of considerable benefit to these patients not to have to travel to a regional centre for stent implantation.

Coral calcifying fluid pH dictates response to ocean acidification.

Ocean acidification driven by rising levels of CO2 impairs calcification, threatening coral reef growth. Predicting how corals respond to CO2 requires a better understanding of how calcification is controlled. Here we show how spatial variations in the pH of the internal calcifying fluid (pHcf) in coral (Stylophora pistillata) colonies correlates with differential sensitivity of calcification to acidification. Coral apexes had the highest pHcf and experienced the smallest changes in pHcf in response to acidification. Lateral growth was associated with lower pHcf and greater changes with acidification. Calcification showed a pattern similar to pHcf, with lateral growth being more strongly affected by acidification than apical. Regulation of pHcf is therefore spatially variable within a coral and critical to determining the sensitivity of calcification to ocean acidification.

Extracellular proteolysis of reelin by tissue plasminogen activator following synaptic potentiation.

The secreted glycoprotein reelin plays an indispensable role in neuronal migration during development and in regulating adult synaptic functions. The upstream mechanisms responsible for initiating and regulating the duration and magnitude of reelin signaling are largely unknown. Here we report that reelin is cleaved between EGF-like repeats 6-7 (R6-7) by tissue plasminogen activator (tPA) under cell-free conditions. No changes were detected in the level of reelin and its fragments in the brains of tPA knockouts, implying that other unknown proteases are responsible for generating reelin fragments found constitutively in the adult brain. Induction of NMDAR-independent long-term potentiation with the potassium channel blocker tetraethylammonium chloride (TEA-Cl) led to a specific up-regulation of reelin processing at R6-7 in wild-type mice. In contrast, no changes in reelin expression and processing were observed in tPA knockouts following TEA-Cl treatment. These results demonstrate that synaptic potentiation results in tPA-dependent reelin processing and suggest that extracellular proteolysis of reelin may regulate reelin signaling in the adult brain.

De novo sirolimus and reduced-dose tacrolimus versus standard-dose tacrolimus after liver transplantation: the 2000-2003 phase II prospective randomized trial.

We studied whether the use of sirolimus with reduced-dose tacrolimus, as compared to standard-dose tacrolimus, after liver transplantation is safe, tolerated and efficacious. In an international multicenter, open-label, active-controlled randomized trial (2000-2003), adult primary liver transplant recipients (n=222) were randomly assigned immediately after transplantation to conventional-dose tacrolimus (trough: 7-15 ng/mL) or sirolimus (loading dose: 15 mg, initial dose: 5 mg titrated to a trough of 4-11 ng/mL) and reduced-dose tacrolimus (trough: 3-7 ng/mL). The study was terminated after 21 months due to imbalance in adverse events. The 24-month cumulative incidence of graft loss (26.4% vs. 12.5%, p=0.009) and patient death (20% vs. 8%, p=0.010) was higher in subjects receiving sirolimus. A numerically higher rate of hepatic artery thrombosis/portal vein thrombosis was observed in the sirolimus arm (8% vs. 3%, p=0.065). The incidence of sepsis was higher in the sirolimus arm (20.4% vs. 7.2%, p=0.006). Rates of acute cellular rejection were similar between the two groups. Early use of sirolimus using a loading dose followed by maintenance doses and reduced-dose tacrolimus in de novo liver transplant recipients is associated with higher rates of graft loss, death and sepsis when compared to the use of conventional-dose tacrolimus alone.

Predicting end-stage renal disease after liver transplant.

Few equations have been developed to predict end-stage renal disease (ESRD) after deceased donor liver transplant. This retrospective observational cohort study analyzed all adult deceased donor liver transplant recipients in the Scientific Registry of Transplant Recipients (SRTR) database, 1995-2010. The prediction equation for ESRD was developed using candidate predictor variables available in SRTR after implementation of the allocation policy based on the model for end-stage liver disease. ESRD was defined as initiation of maintenance dialysis therapy, kidney transplant or registration on the kidney transplant waiting list. We used Cox proportional hazard models to develop separate equations for assessing risk of ESRD by 6 months posttransplant and between 6 months and 5 years posttransplant. Variables in the 6-month equation included recipient age, history of diabetes, history of dialysis before liver transplant, history of malignancy, body mass index, serum creatinine and liver donor risk index. Variables in the 6-month to 5-year equation included recipient race, history of diabetes, hepatitis C status, serum albumin, serum bilirubin and serum creatinine. The prediction equations have good calibration and discrimination (C statistics 0.74-0.78). We have produced risk prediction equations that can be used to aid in understanding the risk of ESRD after liver transplant.

Bortezomib for acute antibody-mediated rejection in liver transplantation.

Antibody-mediated rejection (AMR) is an uncommon, but challenging type of rejection after solid organ transplantation. We review three cases of AMR in ABO-compatible liver transplant recipients. These cases were characterized by severe acute rejection resistant to steroids and antithymocyte globulin, histologic evidence of plasma cell infiltrates, C4d positivity and high serum anti-HLA donor-specific antibodies. All three patients were treated with bortezomib, a proteasome inhibitor effective in depleting plasma cells. After treatment, all patients had improved or normal liver function tests, resolution of C4d deposition and significant decline in their HLA donor-specific antibodies.