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Chronic organ shortage remains the most limiting factor in lung transplantation. To overcome this shortage, a minority of centers have started with efforts to reintroduce donation after circulatory death (DCD). This review aims to evaluate the experimental background, the current international clinical experience, and the further potential and challenges of the different DCD categories. Successful strategies have been implemented to reduce the problems of warm ischemic time, thrombosis after circulatory arrest, and difficulties in organ assessment, which come with DCD donation. From the currently reported results, controlled-DCD lungs are an effective and safe method with good mid-term and even long-term survival outcomes comparable to donation after brain death (DBD). Primary graft dysfunction and onset of chronic allograft dysfunction seem also comparable. Thus, controlled-DCD lungs should be ceased to be treated as marginal and instead be promoted as an equivalent alternative to DBD. A wide implementation of controlled-DCD-lung donation would significantly decrease the mortality on the waiting list. Therefore, further efforts in establishment of legislation and logistics are crucial. With regard to uncontrolled DCD, more data are needed analyzing long-term outcomes. To help with the detailed assessment and improvement of uncontrolled or otherwise questionable grafts after retrieval, ex-vivo lung perfusion is promising.

Background Donor selection criteria are crucial for a successful lung transplant outcome. Our objective was to develop a new donor score to predict short- and long-term survival and validate it with five existing lung donor scores (Oto, Eurotransplant, Minnesota, Maryland-UNOS, Louisville-UNOS). Methods All 454 adult lung transplants at our center between 1992-2015 were included to develop a new score. Discriminative ability for all scores was calculated by the area under time-dependent receiver operating characteristic curves (time-dependent AUC) at 30-day, 1, 5 and 10-year survival, and their fit compared with Akaike's information criterion. For the new score, five pre-selected donor risk factors were derived: age, diabetes mellitus, smoking history, pulmonary infection, PaO$_{2}$/FiO$_{2}$-ratio, weighed via simplification of a multiple Cox model, and shrinkage used to avoid overfitting. The score sub-weighting resulted in a total of 17 points. Results The existing scores showed predictive accuracy better than chance in prediction of survival of 5-year (AUC 0.58-0.60) to 10-year survival (AUC 0.58-0.64). Our new score had better discriminative ability as the existing scores with regard to 1, 5 and 10-year survival (AUC 0.59, 0.64, 0.66, respectively). Additional adjustment for recipient and surgical procedure variables improved the time-dependent AUC's slightly. For the secondary outcomes primary graft dysfunction and bronchiolitis obliterans syndrome, the new score showed also a good predictive accuracy. Conclusions The proposed Zurich Donor Score is simple, well adapted for the current urge of extended donors use, and shows higher discriminative ability compared to preexisting donor scores regarding short- to long-term survival.

As large registries show an increased risk for lung transplant recipients aged 60 years or more, few single centers report favorable outcomes for carefully selected older recipients without providing essential details. The purpose of our study was to determine variables that influence survival in the elderly.All adult bilateral first lung transplants between January 2000 and December 2014 were divided in 2 groups: those aged less than 60 years (N = 223) and those aged 60 years or more (N = 83). The Charlson-Deyo Index determined recipient comorbidities. The Oto Donor Score assessed donor lung quality.Recipients aged 60 years or more had a significant lower median survival compared with their younger counterparts (48 vs 112 months, respectively, P .001). Recipient age was as an exponentially increasing univariate risk factor for mortality. By adjusting for variables in multivariate analysis, this trend was nonsignificant. The displacing variables were idiopathic pulmonary fibrosis (hazard ratio [HR], 1.5; 95% confidence interval [CI], 1.0-2.2), Charlson-Deyo Index 2 or greater (HR, 1.3; 95% CI, 1.0-1.8), systemic hypertension (HR, 1.7; 95% CI, 1.2-2.6), gastroesophageal reflux (HR, 1.9; 95% CI, 1.1-3.1), diverticulosis (HR, 1.7; 95% CI, 1.0-2.7), and an Oto Donor Score 8 or greater (HR, 1.5; 95% CI, 1.1-2.0). All of these risk factors were significantly more likely to occur in recipients aged 60 years or more, except for a tendency for high Charlson-Deyo Index.The comorbidity profile, underlying disease, and donor lung quality appear to be more important than age in reducing long-term survival. Older age serves as a marker for a complex constellation of factors that might be considered the relative or absolute contraindication to lung transplantation rather than age, per se.

Purpose Postoperative cause of death in lung transplantation and time to its occurrence is reported occasionally. This study investigated all causes of death in our lung transplant recipients. Methods All recipients transplanted between 1992 and 2018 were included. Follow-up date was October 2019. Median (min-max) survival was calculated to compare tendencies of incidence between groups. Results Among all 521 transplantations performed, 333 recipients (63.9%) died. Median time from transplantation to death was 40 (0-278) months. Deaths which occurred within 1 month after transplantation were predominantly due to primary graft dysfunction (N=15, 4.5%), followed by cytomegalovirus infection (N=9, 2.7%), major bleeding (N=6, 1.8%) and idiopathic hyperammonemia (N=4, 1.2%). Among all non-cytomegalovirus-infections (N=63, 19.9%), pneumonia (N=36, 10.8%) was the major cause of death, followed by colon perforation (N=12, 3.6%) and cholangitis (N=4, 1.2%). Observation time was median 21(0-230), 11.5(1-278) and 55(28-122) months, respectively. Among patients with malignomas, death due to lymphoma (N=10, 3.0%) occurred after a median of 29.5(12-67) months, death due to carcinoma (N=36, 10.8%) after 92(19-219) months. Cerebrovascular insult/bleeding led to 13 deaths (3.9%) after a median of 9(0-181) months. Death due to acute rejection (N=4, 1.2%) was observed at a median of 9(0-45) months. Chronic lung allograft dysfunction (CLAD) was diagnosed in 129 cases (38.7%), being the largest group with CLAD only as cause of death in 77 patients at a median onset of 53(5-246) months; CLAD and additional infection (N=44, 13.2%) median onset 39(5-145) months; CLAD and additional multi organ dysfunction (N=8, 2.4%) median onset 78(18-198) months. Cardiac (N=19, 5.7%) and renal failures (N=5, 1.5%) occurred late: median 103(0-271) months and 84(17-150) months, respectively. Conclusion There is a large variety of causes of death after lung transplantation with a dominant role of infection, CLAD and carcinoma. With increasing follow-up time, infection becomes less prevalent and CLAD and carcinoma are observed more frequently.

Introduction Lobar lung transplantation (LLTx) allows the use of oversized grafts for small recipients. In this technically demanding and not widely adopted procedure, prolonged air leak, kinking of vascular anastomoses and remaining dead space are frequent complications. We describe our experience in treatening the rarely reported bronchial stump insu!cency (BSI) after LLTx. Case Report Between 1993-2016 we performed 120 cases of LLTx in our center. Among these, 3 developed BSI with empyema. A) 48 year old female with Langerhanscell histiocytosis and BSI of the resected left lower lobe; B) 44 year old male with cystic fibrosis and BSI of the resected right lower lobe; C) 62 year old male with idiopathic pulmonary fibrosis and BSI of the resected right lower lobe. Occurrence of fistula was observed 78 days, 29 days and 39 days after LLTx in A, B and C, respectively. The 3 cases underwent accelerated treatment, consisting of radical debridement of the pleural cavity, packing with wet dressings of diluted 10% povidoneiodine, closure of the bronchial fistula, repeated change of dressings every 2 to 3 days until the chest is macroscopically clean and finally reinforcement of the stump with omentoplasty. Four surgical steps were necessary in case A and C, two in case B. Case A and B recovered well within 6 and 3 days of ICU and had 22 and 39 days overall re-hospitalization, respectively. Case C died 10 days after successful fistula revision due colitis with sepsis in aplasia. Summary A prominent bronchus stump after lower lobectomy in LLTx may cause secretion congestion and focal inflammation that results in BSI. Due to anatomical reasons, a bronchus stump may not be avoided in case of LLTx with right lower lobe resection. Insufficiency can be treated successfully utilizing a multiple stage procedure with suture of the bronchus and covering with omentum flap.

Purpose The Charlson-Deyo-Comorbidity-Index is a popular age independent score to predict long term survival. It incorporates 17 weighted comorbidity conditions and is established in a variety of clinical fields. However, the feasibility for lung transplantation is not yet tested. We therefore validate this score for primary graft dysfunction (PGD), short- to long-term survival and onset of chronic allograft dysfunction (CLAD). Methods The Charleston-Deyo-Comorbidity-Index was assessed in all 466 lung transplant recipients at our center between 1992-2015. Discriminative ability was calculated by the area under the ROC curve (AUC) for 30-day to 10-year survival, severe PGD (grade III) and onset of CLAD. An AUC of 0.5 was considered as non-predictive and 1.0 as maximally predictive. Multiple Cox-regression was used to detect independent risk factors for mortality in the score. All calculations were adjusted for unilateral transplantation, retransplantation, recipient age, idiomatic pulmonary fibrosis, preoperative intensive care unit stay and marginality of the donor (Oto-Donor-Score). Results Median Charslon-Deyo-Comorbidity-Index was 1 (range 1-5). PGD had an AUC of 0.65 (95%CI 0.59-0.72). The predictability increased from 30-day AUC0.58 (95%CI 0.48-0.69) over 1-year AUC0.67 (95%CI 0.60-0.73) to 10-year survival AUC0.72 (95%CI 0.67-0.78). A trend of decreased predictability was observed for onset of CLAD at 1-year AUC0.64 (95%CI 0.55-0.76) to 10-years AUC0.60 (95%CI 0.55-0.66). Multiple Cox-regression revealed the following comorbidities of the index as independent risk factors for mortality: congestive heart failure HR1.40 (95%CI 1.01-1.94), coronary disease needing intervention HR1.72 (95%CI 1.10-2.68), end-stage diabetes mellitus HR5.93 (2.12-19.58), moderate liver disease HR2.53 (95%CI 1.71-3.74) and peripheral vascular disease HR2.43 (95%CI 1.18-5.00). Conclusion The Charlson-Deyo-Comorbidity-Index has a fair prediction for PGD, mid-term survival and onset of CLAD and a good prediction for long term survival after lung transplantation. This score might be used for further clinical decision making in lung allocation. A different weighing and sub-categorization may even improve its prediction.

Purpose Although malignancy is considered a common complication after lung transplantation, profound studies about incidence, characterization, risk assessment and morbidity and mortality are scarce. Therefore we analyze all recipients at our center. Methods All 521 lung transplant recipients at our center between 1992 and 2018 were retrospectively assessed for pre-transplant history and post-transplant onset of malignoma (censor date 01.05.2019). The incidence of occurrence was analyzed using Kaplan-Meier survival. Risk factors to develop a malignoma were assessed by multiple Cox-regression. Results During the observation period, 3.1% (N=16) recipients were transplanted with a history of a cured malignoma, not reoccurring within at least 5 years. After transplantation, 3.1% (N=16) recipient developed a lymphoma, 22.1% (N=115) developed skin cancer and 11.7% (N=63) a non-skin-malignoma. Within non-skin-malignomas, gastrointestinal carcinomas (41.3%, N=26) and lung carcinomas (15.9%, N=10) were the predominant groups. Of note, 6 out of 10 lung carcinomas originated from the donor lung. 6.9% (N=36) of the recipients died of malignoma, accounting for 10.8% of all observed deaths (N=333). The incidence of non-skin-malignancies was after 1 year 2.4%, after 5 years 10.5% and after 10 years 24.4%. The incidence of skin cancer was at 1 year 1.8%, at 5 years 16.3% and at 10 years 35.8%. Multiple Cox-regression revealed that age ≥ 50 years (HR2.8; 95%CI 1.7-4.6) and the underlying diseases of emphysema (HR2.9; 95%CI 1.7-4.9) and interstitial pulmonary fibrosis (HR2.5; 95%CI 1.4-4.6) were independent risk factors to develop a non-skin-maligonoma. Conclusion Post-transplant malignancies are an important reason for morbidity and mortality in lung transplantation. Screening for malignancies during follow up is crucial, especially when considering the increasing risk by the current trend toward an older recipient population, underlying diseases with a smoking history as well as extended donor lungs.

Objectives Lung volume reduction surgery (LVRS) and lung transplantation (LTx) are the treatments of choice in selected patients with end-stage emphysema. Recently, the history of LVRS has been questioned due to reduced post-transplant survival. We aim to address this question by reviewing our experience, which is the largest single-centre series of LVRS followed by LTx. Methods We reviewed our prospectively recorded database in patients with emphysema undergoing LTx between 1993 and 2014. Preoperative workup and postoperative outcomes were compared according to previous LVRS status. The Kaplan-Meier test was used for survival analysis and compared with a log-rank test. Results One hundred and seventeen patients (66 men; mean age 56 ± 7 years) underwent LTx during the study period, 52 of whom had previous LVRS (LVRS + LTx). The mean time from LVRS to LTx was 45 ± 31 months. Patients were slightly older and had extensive smoking history in the LVRS + LTx group. Overall, in-hospital mortality was 10%, which did not differ significantly regardless of the history of LVRS (P = 0.8). The median survival for the LTx-only and LVRS + LTx groups was 86 [95% confidence interval (CI) 56-116] and 107 (95% CI 77-137) months, respectively (P = 0.6). Conclusions Previous LVRS does not negatively affect short-term and long-term outcomes following LTx in patients with end-stage emphysema. The history of LVRS should not preclude the candidacy for LTx. Considering the limited number of donors available, the LVRS option should be kept in mind for the postponement of LTx in carefully selected patients.

OBJECTIVES Overall, emphysema (EMP) is the most common indication for lung transplantation. The majority of patients present with chronic obstructive pulmonary disease (COPD) and less frequently with alpha-1 antitrypsin deficiency (A1ATD). We analysed the results of lung transplants performed for EMP in order to identify the impact of age on short- and long-term outcome. METHODS A retrospective analysis was undertaken of the 108 consecutive lung transplants for EMP performed at our institution from November 1992 to August 2013 (77 COPD, 31 A1ATD). Retransplantations were excluded. RESULTS The median age was 56 years (range 31-68). Thirty-day mortality rate was 3.7%. One- and 5-year survival rates in COPD and A1ATD recipients were comparable (P = 0.8). The 1- and 5-year survival rates for recipients aged