Extracorporeal membrane oxygenation (ECMO) is currently accepted in lung transplantation either to bridge patients to transplantation or to treat postoperatively arising severe primary graft failure. Based on promising initial experiences we have since 2001 implemented ECMO as the standard of intraoperative extracorporeal support in lung transplantation (LuTX) patients with haemodynamic or respiratory instability with the potential to prolong ECMO support into the perioperative period. The aim of this paper is to summarise our total experience with the use of ECMO in LuTX. We retrospectively reviewed all 306 patients undergoing primary lung transplantation from 1/2001 to 1/2006 with regard to the different forms of ECMO use. Results of all patients requiring ECMO were compared to those without ECMO during the observation period. ECMO was used in 147 patients in total. Two patients were bridged to transplantation. A total of 130 patients received intraoperative ECMO support. In 51 of these patients ECMO was prolonged into the perioperative period. Five of these patients required ECMO support again in the postoperative period due to graft dysfunction. Contrary cardiopulmonary bypass was used in 27 patients mainly with concomitant cardiac defects. Eleven of these patients needed therapeutic ECMO in the further course. A total of 149 patients without relevant risk factors were transplanted without any intraoperative extracorporeal support. Six of these patients required ECMO support in the postoperative period for treatment of primary graft dysfunction. Overall 3-month, 1-year and 3-year survival rates were 88.6%, 82.1% and 74.63%. The mentioned survival rates were 85.4%, 74.2% and 67.6% in the intraoperative+/-prolonged ECMO group; 93.5%, 91.9% and 86.5% in the no support group and 74.0%, 65.9% and 57.7% in the CPB group. ECMO is a valuable tool in lung transplantation providing the potential to bridge patients to transplantation, to replace CPB with at least equal results and to overcome severe postoperative complications. Favourable survival rates can be achieved despite the fact that ECMO is used in the more complex patient population undergoing lung transplantation as well as to overcome already established severe complications.

Ex vivo lung perfusion (EVLP) provides the ability to evaluate donor lungs before transplantation. Yet, limited prospective clinical data exist with regard to its potential to recondition unacceptable donor lungs. This paper summarizes the results of a prospective study of lung transplantation using only initially unacceptable donor lungs, which were improved by EVLP for 2–4 h. From March 2010–June 2011, 13 lungs were evaluated ex vivo. Median donor PaO₂ at FiO₂1.0/PEEP5 was 216 mmHg (range 133–271). Four lungs, all with trauma history, showed no improvement and were discarded. Nine lungs improved to a ΔPO₂ higher than 350 mmHg. Median PvO₂ at final assessment in these lungs was 466 mmHg (range 434–525). These lungs were transplanted with a median total ischemic time of 577 min (range 486–678). None of the patients developed primary graft dysfunction grades 2 or 3 within 72 h after transplantation. One patient with secondary pulmonary hypertension was left on a planned prolonged extracorporeal membrane oxygenation postoperatively. Median intubation time was 2 days. Thirty-day mortality was 0%. During the observation period, 119 patients received standard lung transplantation with comparable perioperative outcome. EVLP has a significant potential to improve the quality of otherwise unacceptable donor lungs.

The evolutionary processes that underlie the marked sensitivity of small cell lung cancer (SCLC) to chemotherapy and rapid relapse are unknown^1–3. Here we determined tumour phylogenies at diagnosis and throughout chemotherapy and immunotherapy by multiregion sequencing of 160 tumours from 65 patients. Treatment-naive SCLC exhibited clonal homogeneity at distinct tumour sites, whereas first-line platinum-based chemotherapy led to a burst in genomic intratumour heterogeneity and spatial clonal diversity. We observed branched evolution and a shift to ancestral clones underlying tumour relapse. Effective radio- or immunotherapy induced a re-expansion of founder clones with acquired genomic damage from first-line chemotherapy. Whereas TP53 and RB1 alterations were exclusively part of the common ancestor, MYC family amplifications were frequently not constituents of the founder clone. At relapse, emerging subclonal mutations affected key genes associated with SCLC biology, and tumours harbouring clonal CREBBP/EP300 alterations underwent genome duplications. Gene-damaging TP53 alterations and co-alterations of TP53 missense mutations with TP73, CREBBP/EP300 or FMN2 were significantly associated with shorter disease relapse following chemotherapy. In summary, we uncover key processes of the genomic evolution of SCLC under therapy, identify the common ancestor as the source of clonal diversity at relapse and show central genomic patterns associated with sensitivity and resistance to chemotherapy.