Lung Transplantation With Grafts From Elderly Donors: A Single-Center Experience

Introduction

Use of extended criteria donors is one of the strategies to face the scarcity of donors for lung transplantation.

Methods

Between November 2002 and May 2009, we performed 52 LTs in 50 recipients, 10 of whom (group A) received lungs from donors aged 55 years or older (median, 58.5; range, 56-66 years) for comparison with 28 patients (group B) transplanted with lungs from donors younger than 55 years (median, 25.5; range, 15-54 years). We excluded 9 children and 3 recipients of combined liver plus lung transplantations from the study.

Results

Recipient age, gender, and indications for transplantation did not differ significantly between the 2 groups. Neither were there significant differences in PaO2/FiO2 ratios before lung retrieval, or length of the ischemic time The first PaO2/FiO2 on arrival to the intensive care unit (ICU) and the median length of ICU stay were similar. All patients, except 2 who died in the operating theatre, were extubated between 3 and 216 hours after the transplantation. Hospital mortality was similar in both groups: 3 patients in group A and 2 in group B (P = .1). The median portions of the predicted 1-second forced expiratory volume (FEV1) at 6 months after transplantation did not differ in the 2 groups: 62.4% in group A versus 70% in group B (P = .85).

Conclusion

Lung grafts from donors older than 55 years can be effectively used for transplantation, thus increasing the total organ pool.     

Lung Transplant From Donor With Tracheal Bronchus: Case Report and Literature Review

Donor lung abnormalities are quite rare; one of them is the presence of bronchial anomalies, whose incidence range is from 0.1% to 0.5%. The upper right tracheal bronchus is one of the most frequent anatomic variations. We present a case of successful double lung transplant in a young female patient affected by cystic fibrosis from a donor with upper right tracheal bronchus, emerging 2 rings before the tracheal carina. During implantation of the left lung, we performed a double apical segmentectomy on back table; therefore, the right lung was implanted with the standard technique. Four cases of graft transplant characterized by the presence of tracheal bronchus are reported in the scientific literature; the authors report 4 different technical solutions to tackle the problem of anatomic anomaly. We report the first case of graft segmentectomy at back table suggesting a simple, safe, and time-sparing procedure.In conclusion, provided that the team has sufficient skill in reductive surgery at the back table and the anthropometric data are permissive, we stress the opportunity to downsize the graft in order to minimize anastomotic risks and save time.     

Deceased Donor Organ Transplantation With Expanded Criteria Donors: A Single-Center Experience From India

Introduction

Deceased donor organ transplantation (DDOT) accounts for <4% of renal transplants in India. Many volunteers come forth for organ donation with increasing awareness; unfortunately, the majority are marginal donors, but their rejection would hamper the DDOT program. Judicious use of marginal organs is a challenge for developing countries.

Patients and Methods

We performed 29 renal transplants from 21 expanded criteria donors (ECD) out of 115 DDOT between January 2006 to April 2009—10 dual (DKT) and 19 single (SKT). Fourteen donors had hypertension, a cerebrovascular accident as the cause of death, 9 had both, and 4 had diabetes. Mean donor age was 70.3 ± 8.9 years. Decisions on the procedure were based upon frozen section biopsy in 13 of 21 donors. Mean DKT donor age was 76 ± 9.7 years versu 64 ± 5.7 years of SKT donors. The native kidney diseases were chronic glomerulonephritis (n = 14), diabetic nephropathy (n = 7), tubulointerstitial nephritis (n = 4) and polycystic kidney disease, focal segmental glomerulosclerosis, lupus nephritis and patchy cortical necrosis, (n = 1 each). Mean recipient age of DKT versus SKT was 43.5 versus 42.3 years. All recipients received rabbit anti-thymocyte globulin, followed by steroid, mycophenolate mofetil/calcinueurin inhibitor.

Results

Over a mean follow-up of 341 days, the mean serum creatinine (SCr) of 25/29 patients was 1.60 mg/dL (range, 1.0-2.6). The mean SCr of SKT patients was 1.59 ± 0.63 mg/dL and of DKT, 1.62 ± 0.48 mg/dL. Ten patients had delayed graft function and 11 had biopsy proven acute tubular necrosis. Seven (24%) patients had rejection (grade 3 Banff update '05, type IA; 4, type 2A); 6 responded to antirejection; 1 graft was lost at 7 months due to chronic rejection. Three (10.3%) patients were lost, 1 each due to AMI, sepsis, and CMV disease.

Conclusion

In the circumstances of organ shortage, DDOT with expanded criteria donor is a feasible option.     

Factors Associated With Waiting Time to Deceased Donor Kidney Transplantation in Transplant Candidates

Although a nationwide activation system has been developed to increase deceased donor kidney transplantation (DDKT), there is still enormous discrepancy between transplant need and deceased donor supply in Korea, and therefore waiting time to DDKT is still long. We need to determine the current status of waiting time and the risk factors for long waiting time. We retrospectively analyzed the medical records of the patients on the wait list for DDKT at the Seoul National University Hospital from 2000 to 2017. Among 2,211 wait-listed patients, 606 (27.5%) received DDKT and mean waiting time to DDKT was 45 months. Among them, blood type A was most prevalent (35.6%) and type AB was the least (14.0%). Panel-reactive assay (PRA) was positive in 59 (11.0%) in the first transplant group and 25 (35.0%) in retransplant group. Waiting time in PRA-positive recipients was 63 and 66 months in the first transplant group and retransplant group, respectively. However, waiting time for patients with negative PRA was 42.8 months. Waiting time was shorter in blood type AB (39 months) than other types (46 months). Waiting time was the shortest in children and adolescents. Among patients who were still on the wait list, retransplantation candidates, especially with PRA higher than 50%, had longer waiting time than first transplant candidates. In conclusion, non-AB blood type, positive PRA, and adult age were significantly associated with long waiting time. Therefore, it is necessary to establish a management strategy such as tailored desensitization for highly sensitized patients on the wait list to reduce their waiting time.     

Onset of Inflammation With Ischemia: Implications for Donor Lung Preservation and Transplant Survival

Lungs stored ahead of transplant surgery experience ischemia. Pulmonary ischemia differs from ischemia in the systemic organs in that stop of blood flow in the lung leads to loss of shear alone because the lung parenchyma does not rely on blood flow for its cellular oxygen requirements. Our earlier studies on the ischemia‐induced mechanosignaling cascade showed that the pulmonary endothelium responds to stop of flow by production of reactive oxygen species (ROS). We hypothesized that ROS produced in this way led to induction of proinflammatory mediators. In this study, we used lungs or cells subjected to various periods of storage and evaluated the induction of several proinflammatory mediators. Isolated murine, porcine and human lungs in situ showed increased expression of cellular adhesion molecules; the damage‐associated molecular pattern protein high‐mobility group box 1 and the corresponding pattern recognition receptor, called the receptor for advanced glycation end products; and induction stabilization and translocation of hypoxia‐inducible factor 1α and its downstream effector VEGFA, all of which are participants in inflammation. We concluded that signaling with lung preservation drives expression of inflammatory mediators that potentially predispose the donor lung to an inflammatory response after transplant.     

Outcome After Lung Transplantation From a Donor With Bacterial Pneumonia Under the Japanese Donor Evaluation System

BackgroundIn Japan, a unique medical consultant system for donor evaluation and management has been developed in an effort to maximize the use of extended criteria donor lungs. The aim of this study was to investigate the impact of donor pneumonia (DP) on the outcome after lung transplantation under this system.Materials and MethodsClinical data of 85 patients who underwent deceased donor lung transplantation (41 single and 44 bilateral lung transplants) between August 2012 and March 2018 were reviewed. DP was defined as the recognition of pneumonia on imaging with positive bacterial culture in the airway at the time of transplantation.ResultsTwenty-three transplanted lung grafts were recognized as having DP (27.1%). Serial chest x-rays at the donor hospital did not show deteriorating infiltration or consolidation. The PaO₂/FiO₂ ratio at brain death evaluations were similar between the donor pneumonia (DP) negative (-) and donor pneumonia (DP) positive (+) groups. Perioperative antibiotics were effective against 94% of isolated bacteria. The duration of postoperative antibiotics therapy was longer in the DP (+) group (P = .02). The incidence of primary graft dysfunction and acute rejection, intensive care unit stay, chronic lung allograft dysfunction–free survival, and overall survival were similar between the DP (+) and DP (?) groups.ConclusionsTransplantation of donor lung grafts harboring pneumonia but having a similar oxygenation level to those without pneumonia was safely performed and did not affect long-term outcome. Appropriate evaluation of serial imaging at donor hospital and suitable perioperative antibiotic management may be reasons for this outcome.     

Technical Modifications of the Orthotopic Lung Transplantation Model in Rats With Brain-Dead Donors

BackgroundMicrosurgical lung transplantation in rats has allowed us to obtain new knowledge about lung transplantation. However, some aspects in human transplantation technique still have not been included in this model, which could interfere with the clinical interpretation and extrapolation of results.MethodsTwenty left lung transplantations were performed with a cuff technique and technical modifications, such as brain death induction, the control of ischemia time and retrograde perfusion in the donor and the controlled sequential reperfusion of the implanted lung in the recipient.ResultsSurvival rate was 80%. The transplanted lungs showed proper perfusion and ventilation with good permeability of the anastomoses. Signs of ischemia-reperfusion injury were observed in all animals while mild acute rejection was seen in half of them.ConclusionsThe shown model proves valid and is very similar to the procedure carried out in humans, which would reduce the number of possible variables derived from the surgical technique when extrapolating the study results to clinical use.     

Prevalence,Clinical Characteristics,and Outcomes Among Lung Transplant Recipients of Donors With Cocaine Use

IntroductionThere is limited data regarding lung transplant (LT) outcomes among recipients of donors with a history of cocaine use. We sought to assess the burden of cocaine abuse among LT donors, describe their characteristics, and evaluate the association with post-transplant outcomes.MethodsFrom the United Network for Organ Sharing database, we included adult patients (age ≥18 years) who underwent LT between 1996 and 2014 (N = 20,106; mean age 53.7 ± 13 years; male: 57%). Study groups were divided based on the donor history of recent cocaine abuse (last 6 months). Donor and recipient characteristics were compared between the 2 groups. With 1-year survival as the primary endpoint, multivariate logistic regression analysis was conducted to assess for an independent association with the donor history of cocaine use.ResultsThe overall frequency of donors with any history of cocaine use was 10.9% (n = 2189), although less than half were current users (n = 1001, 4.98%). Unadjusted 1-year survival was worse among recipients of donors with current cocaine use, although it did not achieve statistical significance (84.4% vs 82.2%; odds ratio 1.17, 95% confidence interval 0.99-1.38; P = .07). After adjusting for potential confounders, the current use of cocaine was not associated with 1-year survival (adjusted OR 1.06, 95% CI 0.95-1.18; P = .29).ConclusionsA significant proportion of lung donors have a history of cocaine abuse. Although unadjusted early outcomes appear to worsen among recipients of active cocaine users, an independent association was not seen with 1-year survival. The current analysis supports the continued use of donors with a history of cocaine abuse, assuming they meet other criteria for organ quality.     

Long-Term Outcomes of Clinical Transplantation of Pancreatic Islets With Uncontrolled Donors After Cardiac Death: A Multicenter Experience in Japan

Background

Pancreatic islet transplantation has emerged as an effective treatment for type 1 diabetes mellitus, but its use is limited due to an insufficient supply of cadaveric pancreata. In Japan, uncontrolled donors after cardiac death (DCD) are not deemed to be suitable for whole-organ pancreatic transplantation, and can provide a source of pancreas for islet transplantation. However, the long-term outcomes and utility of uncontrolled DCD in the clinical setting remain controversial. Here, we summarize the long-term outcomes of islet transplantation employing uncontrolled DCD as reported to the Japan Islet Transplantation Registry.

Methods

Sixty-four isolations and 34 transplantations of pancreatic islets were conducted in 18 subjects with type 1 diabetes mellitus under the cover of immunosuppression with basiliximab, sirolimus, and tacrolimus. All donors were uncontrolled DCD at the time of harvesting. The mean follow-up time was 76 months.

Results

Of the 18 recipients, 8, 4, and 6 recipients received 1, 2, and 3 islet infusions, respectively. Overall graft survivals (defined as a C-peptide level ≥0.3 ng/mL) were 72.2%, 44.4%, and 22.2% at 1, 2, and 5 years, respectively, whereas the corresponding graft survivals after multiple infusions were 90.0%, 70.0%, and 30.0%, respectively. Three of these recipients achieved insulin independence in 14, 79, and 215 days. Hb_A1c levels and the requirement of exogenous insulin were improved before loss of graft function. All recipients became free of severe hypoglycemia unawareness, however, at least 5 of 14 patients who had graft failure experienced recurrence of severe hypoglycemia after the loss of graft function.

Conclusions

Islet transplantation from DCD can relieve glucose instability and problems with hypoglycemia when the graft is functioning. However, islets from uncontrolled DCD may be associated with reduced long-term graft survival. Further improvements in the clinical outcome by modification of islet isolation/transplantation protocols are necessary to establish islet transplantation using DCD.     

Extended Criteria Donors in Liver Transplantation: Adapting Donor Quality and Recipient

Despite the progressive increase in the number of liver transplantations, the mortality on the waiting list remains between 5% and 10%, and patients have to deal with longer waiting periods. Facing this situation, transplant centers have developed alternatives to increase the number of grafts by accepting donors who were previously considered to be inadequate, because they are at higher risk of initial poor function and graft failure or may cause disease transmission. Currently, some marginal donors are being routinely used: elderly donors, steatotic grafts, non-heart-beating donors, hepatitis C virus-positive (HCV+) or hepatitis B core antibody-positive donors. These so-called marginal or extended-criteria donors were initially used in high-risk or urgent recipients; however, the number of marginal grafts has significantly increased, forcing the transplant community toward their more rationale use to maintain excellent results of liver transplantation. In this new scenario, the adequacy between donor and recipient may be paramount. Advanced donor age seems to be related to a greater graft failure rate in HCV+ recipients. Early survival seems to be significantly reduced when steatotic grafts are used in recipients with high Model for End-stage Liver Disease (MELD) scores. Moreover, a decreased survival has been observed among high-risk patients receiving organs from marginal donors. No benefit seems to exist when high-donor risk index grafts are transplanted into recipients with low MELD Scores. The recognition of various donor groups according to their quality and the need for good donor and recipient selection must lead us to define new policies for organ allocation of marginal grafts that may come into conflict with current policies of organ allocation according to the risk of death among patients awaiting a liver transplantation.