Image-guided high-dose-rate brachytherapy for rectal cancer: technical note and first clinical experience on an organ-preserving approach.

PURPOSE: As the population ages, the incidence of rectal cancer among elderly patients is rising. Due to the risk of perioperative morbidity and mortality, alternative nonoperative treatment options have been explored in elderly and frail patients who are clinically inoperable or refuse surgery. METHODS: Here we present technical considerations and first clinical experience after treating a cohort of six rectal cancer patients (T1­3, N0­1, M0; UICC stage I-IIIB) with definitive external-beam radiation therapy (EBRT) followed by image-guided, endorectal high-dose-rate brachytherapy (HDR-BT). Patients were treated with 10-13â€¯× 3 Gy EBRT followed by HDR-BT delivering 12-18 Gy in two or three fractions. Tumor response was evaluated using endoscopy and magnetic resonance imaging of the pelvis. RESULTS: Median age was 84 years. All patients completed EBRT and HDR-BT without any high-grade toxicity (> grade 2). One patient experienced rectal bleeding (grade 2) after 10 weeks. Four patients (67%) demonstrated clinical complete response (cCR) or near cCR, there was one partial response, and one residual tumor and hepatic metastasis 8 weeks after HDR-BT. The median follow-up time for all six patients is 42 weeks (range 8-60 weeks). Sustained cCR without evidence of local regrowth has been achieved in all four patients with initial (n)cCR to date. CONCLUSION: Primary EBRT combined with HDR-BT is feasible and well tolerated with promising response rates in elderly and frail rectal cancer patients. The concept could be an integral part of a highly individualized and selective nonoperative treatment offered to patients who are not suitable for or refuse surgery.

Stop the rot. Enzyme inactivation at brain harvest prevents artifacts: A guide for preservation of the in vivo concentrations of brain constituents.

Post-mortem metabolism is widely recognized to cause rapid and prolonged changes in the concentrations of multiple classes of compounds in brain, that is, they are labile. Post-mortem changes from levels in living brain include components of pathways of metabolism of glucose and energy compounds, amino acids, lipids, signaling molecules, neuropeptides, phosphoproteins, and proteins. Methods that stop enzyme activity at brain harvest were developed almost 50 years ago and have been extensively used in studies of brain functions and diseases. Unfortunately, these methods are not commonly used to harvest brain tissue for mass spectrometry-based metabolomic studies or for imaging mass spectrometry studies (IMS, also called mass spectrometry imaging, MSI, or matrix-assisted laser desorption/ionization-MSI, MALDI-MSI). Instead these studies commonly kill animals, decapitate, dissect out brain and regions of interest if needed, then 'snap' freeze the tissue to stop enzymatic activity after harvest, with post-mortem intervals typically ranging from ~0.5 to 3 min. To increase awareness of the importance of stopping metabolism at harvest and preventing the unnecessary complications of not doing so, this commentary provides examples of labile metabolites and the magnitudes of their post-mortem changes in concentrations during brain harvest. Brain harvest methods that stop metabolism at harvest eliminate post-mortem enzymatic activities and can improve characterization of normal and diseased brain. In addition, metabolomic studies would be improved by reporting absolute units of concentration along with normalized peak areas or fold changes. Then reported values can be evaluated and compared with the extensive neurochemical literature to help prevent reporting of artifactual data.

Long-term Outcomes of Laser Ablation of Fistula Tract for Fistula-in-Ano: A Considerable Option in Sphincter Preservation.

BACKGROUND: Ablation of anal fistula tract using a radial laser-emitting probe is a sphincter-preserving technique. OBJECTIVE: The purpose of this study was to assess long-term outcomes of laser ablation of fistula tract. DESIGN: This was a retrospective analysis of the long-term outcomes of 100 patients who underwent laser ablation of fistula tract. SETTINGS: This was a single-center study from a tertiary center in Turkey. PATIENTS: All of the patients with fistula-in-ano were included. Exclusion criteria were the presence of perianal abscess, underlying Crohn's disease, fistula tract <2 cm, fistulas suitable for simple fistulotomy, and intersphincteric fistulas originated from posterior located chronic anal fissure. INTERVENTIONS: A probe housing a 15-watt laser emitting at a wavelength of 1470 nm and an energy level of 100 to 120 joule/cm was used. MAIN OUTCOME MEASURES: No discharge, no symptoms, and fibrotic scar on skin where previously an external opening was present were defined as overall complete healing. All results other than overall complete healing were accepted as failure. RESULTS: A total of 100 patients underwent laser ablation of fistula tract with a median age of 42 years (range, 21-83 y). The majority of them were men. The overall success rate was 62% (95% CI, 52%-71%) in a median follow-up time of 48 months (range, 6-56 mo). None of the patients experienced permanent major or minor anal incontinence. LIMITATIONS: The retrospective nature of this study is its main limitation. Other limitations consist of phone interview for follow-up of the majority of the patients, single-institution data, and the relatively small number of patients. CONCLUSIONS: Laser ablation of the fistula tract is a sphincter-preserving procedure with an acceptable long-term success rate. See Video Abstract at http://links.lww.com/DCR/B186. RESULTADOS A LARGO PLAZO DE LA ABLACIóN CON LáSER DEL TRACTO EN LA FíSTULA ANAL: UNA CONSIDERABLE OPCIóN EN LA PRESERVACIóN DEL ESFíNTER: La ablación con una sonda radial emisora de láser del tracto de fístula anal, es una técnica de preservación del esfínter.Evaluar los resultados a largo plazo de la ablación con láser del tracto fistuloso.Análisis retrospectivo de los resultados a largo plazo de 100 pacientes que se sometieron a la ablación con láser del tracto de fístula.Este es un estudio de centro único de un centro terciario en Turquía.Fueron incluidos todos pacientes con fístula anal. Los criterios de exclusión fueron la presencia de absceso perianal, enfermedad de Crohn subyacente, tracto de fístula menor de 2 cm, fístulas adecuadas para fistulotomía simple y fístulas interesfintéricas originadas en una fisura anal crónica posterior.Se utilizó una sonda que alberga un láser de 15 vatios que emite a una longitud de onda de 1,470 nm y un nivel de energía de 100-120 julios / cm.Sin secreción, sin síntomas y la cicatriz fibrótica en la piel, donde anteriormente estaba presente la apertura externa, se definió como "curación completa general." Todos los resultados que no sean "curación completa en general" se aceptaron como fracaso.Cien pacientes fueron sometidos a ablación con láser del tracto de fístula anal, con una edad media de 42 (21-83) años. La mayoría de ellos fueron varones. La tasa de éxito general fue del 62% (intervalo de confianza del 95%, 52%-71%) en una mediana de tiempo de seguimiento de 48 (6-56) meses. Ninguno de los pacientes experimentó incontinencia anal mayor o menor permanente.La naturaleza retrospectiva de este estudio es su principal limitación. Otras limitaciones consisten en una entrevista telefónica para el seguimiento de la mayoría de los pacientes, datos de una sola institución y un número relativamente pequeño de pacientes.La ablación con láser del tracto de la fístula anal, es un procedimiento de preservación del esfínter y con una aceptable tasa de éxito a largo plazo. Consulte Video Resumen en http://links.lww.com/DCR/B186. (Traducción-Dr Fidel Ruiz Healy).

Cardioprotection via Metabolism for Rat Heart Preservation Using the High-Pressure Gaseous Mixture of Carbon Monoxide and Oxygen.

The high-pressure gas (HPG) method with carbon monoxide (CO) and oxygen (O2) mixture maintains the preserved rat heart function. The metabolites of rat hearts preserved using the HPG method (HPG group) and cold storage (CS) method (CS group) by immersion in a stock solution for 24 h were assessed to confirm CO and O2 effects. Lactic acid was significantly lower and citric acid was significantly higher in the HPG group than in the CS group. Moreover, adenosine triphosphate (ATP) levels as well as some pentose phosphate pathway (PPP) metabolites and reduced nicotinamide adenine dinucleotide phosphate (NADPH) were significantly higher in the HPG group than in the CS group. Additionally, reduced glutathione (GSH), which protects cells from oxidative stress, was also significantly higher in the HPG group than in the CS group. These results indicated that each gas, CO and O2, induced the shift from anaerobic to aerobic metabolism, maintaining the energy of ischemic preserved organs, shifting the glucose utilization from glycolysis toward PPP, and reducing oxidative stress. Both CO and O2 in the HPG method have important effects on the ATP supply and decrease oxidative stress for preventing ischemic injury. The HPG method may be useful for clinical application.

Use of ex vivo normothermic machine perfusion after normothermic regional perfusion to salvage a poorly perfused DCD kidney.

Normothermic regional perfusion (NRP) and normothermic machine perfusion (NMP) have both been used in the procurement and conditioning of abdominal organs from donation after circulatory death donors with reported improved outcomes for the recipients. Here, we describe an unusual case of a kidney that underwent NMP after NRP. After 2 hours of abdominal NRP, the intra-abdominal organs were cold flushed in situ. The liver and right kidney were well flushed, but the left kidney was poorly flushed. Further attempts to clear the left kidney by flushing on the backtable were unsuccessful, and the kidney was thought to be unsuitable for transplant. The left kidney then underwent a 1-hour period of NMP using a red cell-based perfusate. During NMP, the kidney met previously described quality assurance criteria for transplant with good global perfusion and adequate renal blood flow and urine production. The kidney was transplanted into a suitable recipient who had slow early graft function but did not require dialysis posttransplant. The recipient was discharged 6 days posttransplant, and the serum creatinine level was 160 µmol/L (1.8 mg/dL) at 2 months posttransplant.

The effect on early renal function of various dynamic preservation strategies in a preclinical pig ischemia-reperfusion autotransplant model.

The aims of this study were to determine the most optimal timing to start machine perfusion during kidney preservation to improve early graft function and to evaluate the impact of temperature and oxygen supply during machine perfusion in a porcine ischemia-reperfusion autotransplant model. The left kidney of an approximately 40-kg female Belgian Landrace pig was exposed to 30 minutes of warm ischemia via vascular clamping and randomized to 1 of 6 study groups: (1) 22-hour static cold storage (SCS) (n = 6), (2) 22-hour hypothermic machine perfusion (HMP) (n = 6), (3) 22-hour oxygenated HMP (n = 7), (4) 20-hour HMP plus 2-hour normothermic perfusion (NP) (n = 6), (5) 20-hour SCS plus 2-hour oxygenated HMP (n = 7), and (6) 20-hour SCS plus 2-hour NP (n = 6). Graft recovery measured by serum creatinine level was significantly faster for continuous HMP preservation strategies compared with SCS alone and for all end-ischemic strategies. The active oxygenated 22-hour HMP group demonstrated a significantly faster recovery from early graft function compared with the 22-hour nonactive oxygenated HMP group. Active oxygenation was also found to be an important modulator of a faster increase in renal flow during HMP preservation. Continuous oxygenated HMP applied from the time of kidney procurement until transplant might be the best preservation strategy to improve early graft function.

Retrieval Practice or Overall Donor and Recipient Risk: What Impacts on Outcomes After Donation After Circulatory Death Liver Transplantation in the United Kingdom?

Parameters of retrieval surgery are meticulously documented in the United Kingdom, where up to 40% of livers are donation after circulatory death (DCD) donations. This retrospective analysis focuses on outcomes after transplantation of DCD livers, retrieved by different UK centers between 2011 and 2016. Donor and recipient risk factors and the donor retrieval technique were assessed. A total of 236 DCD livers from 9 retrieval centers with a median UK DCD risk score of 5 (low risk) to 7 points (high risk) were compared. The majority used University of Wisconsin solution for aortic flush with a median hepatectomy time of 27-44 minutes. The overall liver injury rate appeared relatively high (27.1%) with an observed tendency toward more retrieval injuries from centers performing a quicker hepatectomy. Among all included risk factors, the UK DCD risk score remained the best predictor for overall graft loss in the multivariate analysis (P < 0.001). In high-risk and futile donor-recipient combinations, the occurrence of liver retrieval injuries had negative impact on graft survival (P = 0.023). Expectedly, more ischemic cholangiopathies (P = 0.003) were found in livers transplanted with a higher cumulative donor-recipient risk. Although more biliary complications with subsequent graft loss were found in high-risk donor-recipient combinations, the impact of the standardized national retrieval practice on outcomes after DCD liver transplantation was minimal.

The development of a predictive model of graft function in uncontrolled donors after circulatory death: validity of a pulsatile renal preservation machine cut-off value for kidney acceptance.

BACKGROUND: The criteria for kidney suitability in uncontrolled donors after circulatory death (uDCD) procured after regional normothermic perfusion are based on macroscopic appearance and renal haemodynamic values with final renal resistance (FRR). However, these criteria have not been analysed to predict the future graft function. This study presents a model to predict the outcome in uDCD kidneys and define the predictive FRR value. METHODS: All uDCD kidney transplants performed in our hospital from 2004 to 2016 were included. Donors and recipients and pre-transplantation data are described. The endpoint was glomerular filtration rate (GFR) ≥30 mL/min at 6 months after transplantation. RESULTS: A total of 194 recipients were included. FRR in donors ≥60 years old was (mean ± SD) 0.27 ± 0.11 versus 0.22 ± 0.09 mmHg/mL/min in donors <60 years (P = 0.042). Kidney survival was 88.2% versus 84% at 12 months and 60.7% versus 30.8% at 120 months (P = 0.067). For the group of recipients from donors ≥60 years, the FRR was 0.37 ± 0.08 mmHg/mL/min in the GFR <30 mL/min group versus 0.18 ± 0.06 mmHg/mL/min in the GFR ≥30 mL/min group (P < 0.001). The value FRR ≥0.3 mmHg/mL/min predicts 59-79% of GFR <30 mL/min [odds ratio = 2.16, 95% confidence interval (CI) 1.80-6.40; P < 0.001]. The predictive accuracy of FRR for GFR by ROC curve was 0.968 (95% CI). The best cut-off for FRR was 0.3 mmHg/mL/min to predict GFR at 6 months with a sensitivity of 67%, specificity of 100%, positive predictive value of 83% and negative predictive value of 92%. CONCLUSIONS: Our results suggest that in uDCD donors the combination of donor age ≥60 years together with FRR ≥0.3 mmHg/mL/min could predict poor outcome at 6 months after transplantation in low immunological risk recipients.

Outcomes of DCD kidneys recovered for transplantation with versus without pre-mortem heparin administration.

BACKGROUND: Pre-mortem heparin administration during donation after circulatory death (DCD) organ recovery may be particularly important to improve perfusion and prevent graft thrombosis. However, pre-mortem heparin administration is not universally practiced in the US and scarce data exist regarding its efficacy. METHODS: Using a national transplant registry data, we identified DCD kidneys recovered for transplantation from January 1, 2003, to March 10, 2017, and examined discard and outcomes after transplantation using bivariate and multivariable analyses. Organs with unknown or missing donor heparin status (n = 193), seropositive HIV (n = 10), HTLV (n = 33), hepatitis B (n = 26), or hepatitis C (n = 648) were excluded. RESULTS: Of 24 861 DCD kidneys recovered with (n = 22 557) or without pre-mortem heparin administration (n = 2304), discard occurred in 19.1% and 20.8%, respectively (P = 0.05). On multivariate analysis, heparin use was not associated with discard (aOR 1.02, 95% CI 0.89-1.17, P = 0.820). Overall graft survival of no-heparin (n = 1791) vs heparin groups (n = 17 968) was similar on univariate and multivariate analysis (aHR 0.98, 95% CI 0.87-1.09, P = 0.640). CONCLUSION: DCD kidneys from donors that have not received pre-mortem heparin administration have acceptable transplant outcomes and are not associated with discard.

Development of Clinical Criteria for Functional Assessment to Predict Primary Nonfunction of High-Risk Livers Using Normothermic Machine Perfusion.

Increased use of high-risk allografts is critical to meet the demand for liver transplantation. We aimed to identify criteria predicting viability of organs, currently declined for clinical transplantation, using functional assessment during normothermic machine perfusion (NMP). Twelve discarded human livers were subjected to NMP following static cold storage. Livers were perfused with a packed red cell-based fluid at 37°C for 6 hours. Multilevel statistical models for repeated measures were employed to investigate the trend of perfusate blood gas profiles and vascular flow characteristics over time and the effect of lactate-clearing (LC) and non-lactate-clearing (non-LC) ability of the livers. The relationship of lactate clearance capability with bile production and histological and molecular findings were also examined. After 2 hours of perfusion, median lactate concentrations were 3.0 and 14.6 mmol/L in the LC and non-LC groups, respectively. LC livers produced more bile and maintained a stable perfusate pH and vascular flow >150 and 500 mL/minute through the hepatic artery and portal vein, respectively. Histology revealed discrepancies between subjectively discarded livers compared with objective findings. There were minimal morphological changes in the LC group, whereas non-LC livers often showed hepatocellular injury and reduced glycogen deposition. Adenosine triphosphate levels in the LC group increased compared with the non-LC livers. We propose composite viability criteria consisting of lactate clearance, pH maintenance, bile production, vascular flow patterns, and liver macroscopic appearance. These have been tested successfully in clinical transplantation. In conclusion, NMP allows an objective assessment of liver function that may reduce the risk and permit use of currently unused high-risk livers.

Hydrogen Flush After Cold Storage as a New End-Ischemic Ex Vivo Treatment for Liver Grafts Against Ischemia/Reperfusion Injury.

Cold storage (CS) remains the gold standard for organ preservation worldwide, although it is inevitably associated with ischemia/reperfusion injury (IRI). Molecular hydrogen (H2 ) is well known to have antioxidative properties. However, its unfavorable features, ie, inflammability, low solubility, and high tissue/substance permeability, have hampered its clinical application. To overcome such obstacles, we developed a novel reconditioning method for donor organs named hydrogen flush after cold storage (HyFACS), which is just an end-ischemic H2 flush directly to donor organs ex vivo, and, herein, we report its therapeutic impact against hepatic IRI. Whole liver grafts were retrieved from Wistar rats. After 24-hour CS in UW solution, livers were cold-flushed with H2 solution (1.0 ppm) via the portal vein (PV), the hepatic artery (HA), or both (PV + HA). Functional integrity and morphological damages were then evaluated by 2-hour oxygenated reperfusion at 37°C. HyFACS significantly lowered portal venous pressure, transaminase, and high mobility group box protein 1 release compared with vehicle-treated controls (P < 0.01). Hyaluronic acid clearance was significantly higher in the HyFACS-PV and -PV + HA groups when compared with the others (P < 0.01), demonstrating the efficacy of the PV route to maintain the sinusoidal endothelia. In contrast, bile production and lactate dehydrogenase leakage therein were both significantly improved in HyFACS-HA and -PV + HA (P < 0.01), representing the superiority of the arterial route to attenuate biliary damage. Electron microscopy consistently revealed that sinusoidal ultrastructures were well maintained by portal HyFACS, while microvilli in bile canaliculi were well preserved by arterial flush. As an underlying mechanism, HyFACS significantly lowered oxidative damages, thus improving the glutathione/glutathione disulfide ratio in liver tissue. In conclusion, HyFACS significantly protected liver grafts from IRI by ameliorating oxidative damage upon reperfusion in the characteristic manner with its route of administration. Given its safety, simplicity, and cost-effectiveness, end-ischemic HyFACS may be a novel pretransplant conditioning for cold-stored donor organs.

A metabolic approach during normothermic regional perfusion in uncontrolled donors after circulatory death-A pilot study.

The use of donation after circulatory death (DCD) has increased significantly to face the persistent mismatch between supply and demand of organs for transplantation. While controlled (c) DCDs have warm ischemic time (WIT) that can be estimated, the WIT is often inexact and extended in uncontrolled DCD (uDCD), making assessment of injury difficult. We aimed at investigating the effects of cold ischemia on potential donor organ damage in the course of nRP by assessing the dynamic variations of transaminases and creatinine values in 17 uDCD donors. In our series, lactate values did not show significant changes during the study period (P = 0.147). Creatinine values did not significantly changed while transaminases progressive increased throughout the study period, even if it was significant only for AST (P = 0.035). According to our data, nRP duration affects splanchnic organs, being the liver sensitive to hypoperfusion, and serial biochemical measurements could help in detecting organ functional status.

Uncontrolled donation after circulatory death: comparison of two kidney preservation protocols on graft outcomes.

BACKGROUND: Kidney transplantation following uncontrolled donation after circulatory death (uDCD) presents a high risk of delayed graft function due to prolonged warm ischemia time. In order to minimise the effects of ischemia/reperfusion injury during warm ischemia, normothermic recirculation recently replaced in situ perfusion prior to implantation in several institutions. The aim of this study was to compare these preservation methods on kidney graft outcomes. METHODS: The primary endpoint was the one-year measured graft filtration rate (mGFR). We collected retrospective data from 64 consecutive uDCD recipients transplanted over a seven-year period in a single centre. RESULTS: Thirty-two grafts were preserved by in situ perfusion and 32 by normothermic recirculation. The mean ± SD mGFR at 1 year post-transplantation was 43.0 ± 12.8 mL/min/1.73 m2 in the in situ perfusion group and 53.2 ± 12.8 mL/min/1.73 m2 in the normothermic recirculation group (p = 0.01). Estimated GFR levels were significantly higher in the normothermic recirculation group at 12 months (p = 0.01) and 24 months (p = 0.03) of follow-up. We did not find any difference between groups regarding patient and graft survival, delayed graft function, graft rejection, or interstitial fibrosis. CONCLUSIONS: Function of grafts preserved by normothermic recirculation was better at 1 year and the results suggest that this persists at 2 years, although no difference was found in short-term outcomes. Despite the retrospective design, this study provides an additional argument in favour of normothermic recirculation.

A systematic review and meta-analysis of cold in situ perfusion and preservation of the hepatic allograft: Working toward a unified approach.

The efficacy of cold in situ perfusion and static storage of the liver is a possible determinant of transplantation outcomes. The aim of this study was to determine whether there is evidence to substantiate a preference for a particular perfusion route (aortic or dual) or perfusion/preservation solution in donation after brain death (DBD) liver transplantation. The Embase, MEDLINE, and Cochrane databases were used (1980-2017). Random effects modeling was used to estimate effects on transplantation outcomes based on (1) aortic or dual in situ perfusion and (2) the use of University of Wisconsin (UW), histidine tryptophan ketoglutarate (HTK), Celsior, and/or Institut Georges Lopez-1 (IGL-1) solutions for perfusion/preservation. A total of 22 articles were included (2294 liver transplants). The quality of evidence ranged from very low to moderate Grading of Recommendations, Assessment, Development and Evaluations score. Meta-analyses were conducted for 14 eligible studies. Although there was no difference in the primary nonfunction (PNF) rate, a higher peak alanine aminotransferase (ALT) was recorded in dual compared with aortic-only UW-perfused livers (standardized mean difference, 0.24; 95% confidence interval, 0.01-0.47); a back-table portal venous flush was undertaken in the majority of aortic-only perfused livers. There were no relevant differences in peak enzymes, PNF, thrombotic graft loss, biliary complications, or 1-year graft survival in comparisons between dual-perfused livers using UW, HTK, Celsior, or IGL-1. In conclusion, there is no significant evidence that aortic-only perfusion of the DBD liver compromises transplantation outcomes, and it may be favored because of its simplicity. However, there is currently insufficient evidence to advocate for the use of any particular perfusion/preservation fluid over the others. Liver Transplantation 23 1615-1627 2017 AASLD.

Ex-vivo perfusion of donor hearts for human heart transplantation (PROCEED II): a prospective, open-label, multicentre, randomised non-inferiority trial.

BACKGROUND: The Organ Care System is the only clinical platform for ex-vivo perfusion of human donor hearts. The system preserves the donor heart in a warm beating state during transport from the donor hospital to the recipient hospital. We aimed to assess the clinical outcomes of the Organ Care System compared with standard cold storage of human donor hearts for transplantation. METHODS: We did this prospective, open-label, multicentre, randomised non-inferiority trial at ten heart-transplant centres in the USA and Europe. Eligible heart-transplant candidates (aged >18 years) were randomly assigned (1:1) to receive donor hearts preserved with either the Organ Care System or standard cold storage. Participants, investigators, and medical staff were not masked to group assignment. The primary endpoint was 30 day patient and graft survival, with a 10% non-inferiority margin. We did analyses in the intention-to-treat, as-treated, and per-protocol populations. This trial is registered with ClinicalTrials.gov, number NCT00855712. FINDINGS: Between June 29, 2010, and Sept 16, 2013, we randomly assigned 130 patients to the Organ Care System group (n=67) or the standard cold storage group (n=63). 30 day patient and graft survival rates were 94% (n=63) in the Organ Care System group and 97% (n=61) in the standard cold storage group (difference 2·8%, one-sided 95% upper confidence bound 8·8; p=0·45). Eight (13%) patients in the Organ Care System group and nine (14%) patients in the standard cold storage group had cardiac-related serious adverse events. INTERPRETATION: Heart transplantation using donor hearts adequately preserved with the Organ Care System or with standard cold storage yield similar short-term clinical outcomes. The metabolic assessment capability of the Organ Care System needs further study. FUNDING: TransMedics.

Milestones and Basic Principles.

Current shortage in organ donors led to the expansion of criteria for organ donation placing organ preservation as one cornerstone for successful transplant, graft function and survival. The historical work of Belzer and Collins paved the way for key descriptions of physiopathology of cell ischemia and protection (cytokines roles, oxidative stress, energy shift to lactic acidosis and perfusion pressure changes). Good preservation means immediate recovery of function and prevention of chronic rejection. Two cooling approaches are available: static (SCS: simple cold storage) suitable for all organs, and dynamic (HMP: hypothermic machines perfusion) designed for kidneys and liver. A thorough discussion of historically manufactured and widely sold preservation solutions e.g. EuroCollins, UW solution (Viaspan®) as well as current used solutions e.g. Custodiol® and the new Celsior is available in this review. Obviously, every single organ exhibits different tolerance to warm and cold ischemia depending on its nature and demands after transplant. Future perspectives of organ preservation may be hidden in hibernators which may hold the enigmas of perfect human organ preservation.

[Ischemia reperfusion control: the key of kidney graft outcome]. / L'ischémie reperfusion - Acteur essentiel du devenir du greffon rénal.

During the transplantation procedure, ischemia reperfusion is an inevitable situation characterized by specific pathophysiological processes, which ultimately act synergistically to create injuries in the graft. These injuries are involved in early graft dysfunctions which promote chronic dysfunction and compromise graft outcome. Progresses in immunosuppressive drug regimens now place ischemia reperfusion injury control at the forefont for innovative therapeutic strategy to improve the quality of the graft. This review details these different processes and its consequences on renal graft function underlying the interest of novel therapeutic strategy.

Donor risk factors, retrieval technique, preservation and ischemia/reperfusion injury in pancreas transplantation.

PURPOSE OF REVIEW: Pancreas transplantation is still hampered by a high incidence of early graft loss, and organ quality concerns result in high nonrecovery/discard rates. Demographic donor characteristics, surgical retrieval strategy, preservation fluid and ischemia time are crucial factors in the process of organ selection and are discussed in this review. RECENT FINDINGS: The donor shortage is driving an increasing utilization of nonideal organs which would previously have been identified as unsuitable. Recent literature suggests that organs from extended criteria donors - older (>45 years), BMI >30  kg/m(2), and donation after cardiac death (DCD) - can achieve the same graft and patient survival as those from standard criteria donors, with the proviso that the accumulation of risk factors and long ischemic times should be avoided. Visual assessment of the pancreas is advisable before declining/accepting a pancreas. University of Wisconsin represents the gold standard solution; however, histidine-tryptophan-ketoglutarate and Celsior result in equal outcomes if cold ischemia time (CIT) is less than 12  h. Currently in pancreas transplantation, there is no proven effective ischemia/reperfusion injury prophylaxis than trying to keep CIT as short as possible. SUMMARY: Demographic risk factors, inspection of the pancreas by an experienced surgeon and predicted CIT are crucial factors in deciding whether to accept a pancreas for transplantation. However, there is a need for an improved evidence base to determine where to set the 'cut-off' for unsuitable pancreatic grafts.