Factors That Complicated the Implementation of a Program of Donation After Unexpected Circulatory Death of Lungs and Kidneys. Lessons Learned From a Regional Trial in the Netherlands

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Lung Transplantation from Nonheparinized Category III Non-Heart-Beating Donors. A Single-Centre Report

Background. Despite the increasing use of extended lung donors, the shortage of lung donors remains. Usage of non-heart-beating (NHB) lung donors contributes to fight this shortage. We describe our experience in 21 consecutive adult lung transplantations using nonheparinized category III NHB donors and standard flush preservation. Methods. From January 2005 to December 2008, we collected donor and recipient data of all NHB category III lung transplantations performed in Our center. For comparison, we also collected the data of all heart-beating (HB) lung transplantations in the same period. We focused on data describing the donor, the donor procedure, the recipient's primary graft dysfunction, survival, rejection episodes, and the lung graft function. Results. Twenty-one NHB and 77 HB lung transplantations were performed. Circulation arrest occurred after 14 (4-62) min and warm ischemia time was 30 (19-44) min. Occurrence of primary graft dysfunction, acute rejection episodes, development of bronchiolitis obliterans syndrome was equal to the HB cohort as was the 2 years survival of 95% in the NHB group compared with 86% in the H B group. Lung graft function during the first 2 years tended to be better preserved in the NHB group. Conclusion. Category III NHB lung donation is a good alternative in addition to H B lung donation. Using nonheparinized category III NHB donors and standard ante- and retrograde, flush perfusion resulted in good lung graft function and survival. NHB donation offers a great opportunity to reduce the burden of donor lung shortage

Non-heart-beating lung donation:How big is the pool?

Lungs from non-heart-beating (NHB) donors are seldom used in The Netherlands despite the good quality of these organs. Based on a retrospective analysis of 162 NHB donor procedures we found that only 5% of the lungs were actually utilized, but that 30% of the lungs were suitable for transplantation. Not recognizing the suitability of NHB lungs is likely the main reason for their non-availability

Does the meld system provide equal access to liver transplantation for patients with different ABO blood groups?

This study investigates the relationship between blood group and waiting time until transplantation or death on the waiting list. All patients listed for liver transplantation in the Netherlands between 15 December 2006 and 31 December 2012, were included. Study variables were gender, age, year of listing, diagnosis, previous transplantations, blood group, urgency, and MELD score. Using a competing risks analysis, separate cumulative incidence curves were constructed for death on the waiting list and transplantation and used to evaluate outcomes.In 517 listings, the mean death rate per 100 patient-years was 10.4. A total of 375 (72.5% of all listings) were transplanted. Of all transplantations, 352 (93.9%) were ABO-identical and 23 (6.1%) ABO-compatible. The 5-year cumulative incidence of death was 11.2% (SE 1.4%), and of transplantation 72.5% (SE 2.0%). Patient blood group had no multivariate significant impact on the hazard of dying on the waiting list nor on transplantation. Age, MELD score, and urgency status were significantly related to the death on the waiting list and transplantation. More recent listing had higher probability of being transplanted. In the MELD era, patient blood group status does not have a significant impact on liver transplant waiting list mortality nor on waiting time for transplantation

Surgical injuries of postmortem donor livers:Incidence and impact on outcome after adult liver transplantation

The exact frequency and clinical consequences of surgical hepatic injuries during organ procurement are unknown. We analyzed the incidence, risk factors, and clinical outcome of surgical injuries in 241 adult liver grafts. Hepatic injuries were categorized as parenchymal, vascular, or biliary. Outcome variables were bleeding complications, hepatic artery thrombosis (HAT), and graft survival. In 82 livers (34%), 96 injuries were detected. Most injuries were minor, but clinically relevant injuries were detected in 6.6% (16/241) of the livers. Fifty (21%) liver grafts had some degree of parenchymal or capsular injury, 40 (17%) had vascular injury, and 6 (2%) had an injury to the bile duct. Procurement region was the only risk factor significantly associated with surgical injury. The rate of hepatic artery injury was significantly higher in livers with aberrant arterial anatomy. Bleeding complications were found in 18% of patients who received livers with a parenchymal or capsular injury in contrast to 9% without parenchymal injury (P = 0.065). HAT was found in 23% of the patients who received a liver with arterial injury compared to 4% without arterial injury (P = 0.001). Overall graft survival rates were not significantly different for grafts with or without anatomical injury. In conclusion, surgical injuries of donor livers are an underestimated problem in liver transplantation and can be observed in about one-third of all cases. Clinically relevant injuries are detected in 6.6% of all liver grafts. Arterial injuries are associated with an increased risk of HAT

Target volume delineation variation in radiotherapy for early stage rectal cancer in the Netherlands

Purpose: The aim of this study was to measure and improve the quality of target volume delineation by means of national consensus on target volume definition in early-stage rectal cancer. Methods and materials: The CTV's for eight patients were delineated by 11 radiation oncologists in 10 institutes according to local guidelines (phase 1). After observer variation analysis a workshop was organized to establish delineation guidelines and a digital atlas, with which the same observers re-delineated the dataset (phase 2). Variation in volume, most caudal and cranial slice and local surface distance variation were analyzed. Results: The average delineated CTV volume decreased from 620 to 460 cc (p <0.001) in phase 2. Variation in the caudal CTV border was reduced significantly from 1.8 to 1.2 cm SD (p = 0.01), while it remained 0.7 cm SD for the cranial border. The local surface distance variation (cm SD) reduced from 1.02 to 0.74 for anterior, 0.63 to 0.54 for lateral, 0.33 to 0.25 for posterior and 1.22 to 0.46 for the sphincter region, respectively. Conclusions: The large variation in target volume delineation could significantly be reduced by use of consensus guidelines and a digital delineation atlas. Despite the significant reduction there is still a need for further improvement. (C) 2011 Elsevier Ireland Ltd. All rights reserved. Radiotherapy and Oncology 102 (2012) 14-2

Oncogenic K-Ras Turns Death Receptors Into Metastasis-Promoting Receptors in Human and Mouse Colorectal Cancer Cells

BACKGROUND & AIMS: Death receptors expressed on tumor cells can prevent metastasis formation by inducing apoptosis, but they also can promote migration and invasion. The determinants of death receptor signaling output are poorly defined. Here we investigated the role of oncogenic K-Ras in determining death receptor function and metastatic potential. METHODS: Isogenic human and mouse colorectal cancer cell lines differing only in the presence or absence of the K-Ras oncogene were tested in apoptosis and invasion assays using CD95 ligand and tumor necrois factor-related apoptosis-inducing ligand (TRAIL) as stimuli. Metastatic potential was assessed by intrasplenic injections of green fluorescent protein-or luciferase-expressing tumor cells, followed by intravital fluorescence microscopy or bioluminescence imaging, and confocal microscopy and immunohistochemistry. Ras-effector pathway control of CD95 output was assessed by an RNA-interference and inhibitor-based approach. RESULTS: CD95 ligand and TRAIL stimulated invasion of colorectal tumor cells and liver metastases in a K-Ras-dependent fashion. Loss of mutant K-Ras switched CD95 and TRAIL receptors back into apoptosis mode and abrogated metastatic potential. Raf1 was essential for the switch in CD95 function, for tumor cell survival in the liver, and for K-Ras-driven formation of liver metastases. K-Ras and Raf1 suppressed Rho kinase (ROCK)/LIM kinase-mediated phosphorylation of the actin-severing protein cofilin. Overexpression of ROCK or LIM kinase allowed CD95L to induce apoptosis in K-Ras-proficient cells and prevented metastasis formation, whereas their suppression protected K-Ras-deficient cells against apoptosis. CONCLUSIONS: Oncogenic K-Ras and its effector Raf1 convert death receptors into invasion-inducing receptors by suppressing the ROCK/ LIM kinase pathway, and this is essential for K-Ras/Raf1-driven metastasis formatio