Mettu Srinivas Reddy

Peritoneal Cooling May Provide Improved Protection for Uncontrolled Donors After Cardiac Death: An Exploratory Porcine Study

Uncontrolled donation after cardiac death (DCD) renal transplantation relies on rapid establishment of organ preservation interventions. We have developed a model of the uncontrolled DCD, comparing current in situ perfusion (ISP) techniques with additional peritoneal cooling (PC). Ten pigs were killed and subjected to a 2 h ischemia period. The ISP group modeled current DCD protocols. The PC group (PC) modeled current protocols plus PC. Two animals were used as controls and subjected to 2 h of warm ischemia. Core renal temperature and microdialysis markers of ischemia were measured. Preservation interventions began at 30 min, with rapid laparotomy and kidney recovery performed at 2 h, prior to machine perfusion viability testing. The final mean renal temperature achieved in the ISP group was 26.3°C versus 16.9°C in the PC group (p = 0.0001). A significant cryopreservation benefit was suggested by lower peak microdialysate lactate and glycerol levels (ISP vs. PC, p = 0.0003 and 0.0008), and the superiority of the PC group viability criteria (p = 0.0147). This pilot study has demonstrated significant temperature, ischemia protection and viability assessment benefits with the use of supplementary PC. The data suggests a need for further research to determine the potential for reductions in the rates of ischemia‐related clinical phenomena for uncontrolled DCDs.

Dual transplantation of marginal kidneys from nonheart beating donors selected using machine perfusion viability criteria

PURPOSEnViability testing can be used to avoid the transplantation of nonheart beating donor organs that are likely to have primary nonfunction. Such testing also identifies a second group of kidneys which, although unsuitable for solitary transplantation, may be considered for dual transplantation. In kidneys in this group solitary transplants would be unlikely to produce a sufficient glomerular filtration rate to support the recipient. However, if used together as a dual transplant, they have the potential to produce sufficient renal function in 1 patient.nnnMATERIALS AND METHODSnThe group at our unit has performed 23 dual nonheart beating donor renal transplants from 2003 to date. Using 3 and 12-month post-transplantation recipient glomerular filtration rates as primary end points we compared our dual transplant group with our series of 115 single nonheart beating donor transplants from 1998 to 2006.nnnRESULTSnAt 3 and 12 months mean glomerular filtration rates in the dual group were 46.2 and 45.5 ml per minute per 1.73 m(2), respectively. These values were not significantly different from the mean glomerular filtration rates of 40.7 and 43.0 ml per minute per 1.73 m(2), respectively, in the single transplant group.nnnCONCLUSIONSnWe have observed that a subset of nonheart beating donor kidneys that do not satisfy the viability criteria for single organ transplantation may become successful dual organ grafts, thus, avoiding unnecessary organ nonuse and maximizing organ resources.

Pancreas Graft Salvage Using Pancreatico‐Duodenectomy With Enteric Drainage

As demand for donor pancreases increases, attempts are being made to utilize even marginal grafts for transplantation. Injury during pancreas recovery can predispose to posttransplant complications and graft loss. Early recognition and correction can salvage these grafts. The authors report an instance of poor segmental perfusion of the pancreas graft that was salvaged by pancreas head resection and enteric drainage through a Roux‐en‐Y pancreatico‐jejunostomy.

Pembrolizumab for metastatic hepatocellular carcinoma following live donor liver transplantation: The silver bullet?

Treatment options for hepatocellular carcinoma (HCC) recurrence following liver transplantation (LT) are extremely limited. HCCs are a heterogenous group of tumors driven by inflammation and hence the rationale to evaluate immunotherapy in these patients. The immune checkpoint protein, programmed death receptor 1 (PD-1), is an inhibitory molecule expressed on the surface of multiple tissue types and keeps T cells from attacking tumor cells. We report on a case of metastatic HCC following LT that responded dramatically to pembrolizumab, a PD-1 inhibitor, after failure of therapy with sorafenib.

Portal Venous Oxygen Persufflation of the Donation after Cardiac Death pancreas in a rat model is superior to static cold storage and hypothermic machine perfusion

Success of clinical pancreatic islet transplantation depends on the mass of viable islets transplanted and the proportion of transplanted islets that survive early ischaemia reperfusion injury. Novel pancreas preservation techniques to improve islet preservation and viability can increase the utilization of donation after cardiac death donor pancreases for islet transplantation. Rat pancreases were retrieved after 30 min of warm ischaemia and preserved by static cold storage, hypothermic machine perfusion or retrograde portal venous oxygen persufflation for 6 h. They underwent collagenase digestion and density gradient separation to isolate islets. The yield, viability, morphology were compared. In vitro function of isolated islets was compared using glucose stimulated insulin secretion test. Portal venous oxygen persufflation improved the islet yield, viability and morphology as compared to static cold storage. The percentage of pancreases with good in vitro function (stimulation index > 1.0) was also higher after oxygen persufflation as compared to static cold storage. Retrograde portal venous oxygen persufflation of donation after cardiac death donor rat pancreases has the potential to improve islet yield.

Intraoperative cholangiogram to delineate caudate biliary anatomy in donor hepatectomy: Are we shooting for trouble?

We read with interest the article by Makki et al[1], in which they have analysed the caudate lobe biliary anatomy in 500 living liver donors and stressed its importance in reducing post-operative bile leaks. A clear understanding of liver anatomy and improvements in cross-sectional imaging have contributed extensively to the success of split liver transplantation (SLT) and living donor liver transplantation (LDLT). The early experience of SLT and LDLT saw a high incidence of bile leaks attributed to cut surface leaks. In 2008, based on a vast experience in SLT, the senior author of this communication, from Kings college hospital, London proposed an explanation for the high incidence of bile leaks in segmental liver transplantation based on an understanding of the biliary anatomy of caudate lobe. This article is protected by copyright. All rights reserved.

Auxiliary Partial Orthotopic Liver Transplantation for Monogenic Metabolic Liver Diseases: Single-Centre Experience

PURPOSEnAuxiliary partial orthotopic liver transplantation (APOLT) in metabolic liver disease (MLD) has the advantage of correcting the metabolic defect, preserving the native liver for gene therapy in the future with the possibility of withdrawal of immunosuppression.nnnMETHODSnRetrospective analysis of safety and efficacy of APOLT in correcting the underlying defect and its impact on neurological status of children with MLD.nnnRESULTSnA total of 13 APOLT procedures were performed for MLD during the study period. The underlying aetiologies being propionic acidemia (PA)-5, citrullinemia type 1 (CIT1)-3 and Crigler-Najjar syndrome type 1 (CN1)-5 cases respectively. Children with PA and CIT1 had a median of 8 and 4 episodes of decompensation per year, respectively, before APOLT and had a mean social developmental quotient (DQ) of 49 (<3 standard deviations) as assessed by Vineland Social Maturity Scale prior to liver transplantation. No metabolic decompensation occurred in patients with PA and CIT1 intraoperatively or in the immediate post-transplant period on protein-unrestricted diet. Patients with CN1 were receiving an average 8-15xa0h of phototherapy per day before APOLT and had normal bilirubin levels without phototherapy on follow-up. We have 100% graft and patient survival at a median follow-up of 32xa0months. Progressive improvement in neurodevelopment was seen in children within 6xa0months of therapy with a median social DQ of 90.nnnCONCLUSIONSnAPOLT is a safe procedure, which provides good metabolic control and improves the neurodevelopment in children with selected MLD.

Liver Tumors in Children

Liver tumors are uncommon in the pediatric age group and constitute around 1–2 % of all childhood tumors. Pediatric liver tumors have characteristic pathology, which is very rarely seen in adults. There is also a distinct correlation between the type of liver tumor and the age at presentation. Overall, hepatoblastoma is the most common childhood liver tumor. Hepatocellular carcinoma among the malignant tumors and hemangioma among the benign tumors are the other common types. Management of childhood liver tumors is challenging as most tumors present at an advanced stage rendering adult-based liver tumor protocols impractical. Collective efforts by clinicians across the world have helped us in gaining a better understanding of their behavior and have led to significant improvement in outcomes. This is nowhere else more evident than in the case of hepatoblastoma where long-term survival of over 70 % is now routinely achieved. This chapter reviews the types of benign and malignant liver tumors in the childhood, with emphasis on the clinical management of hepatoblastoma.