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OBJECTIVES History of anatomical lung resection complicates lung transplantation (LTx). Our aim was to identify indications, intraoperative approach and outcome in these challenging cases in a retrospective multicentre cohort analysis. METHODS Members of the ESTS Lung Transplantation Working Group were invited to submit data on patients undergoing LTx after a previous anatomical native lung resection between January 2005 and July 2020. The primary end point was overall survival (Kaplan–Meier estimation). RESULTS Out of 2690 patients at 7 European centres, 26 (1%) patients (14 males; median age 33 years) underwent LTx after a previous anatomical lung resection. The median time from previous lung resection to LTx was 12 years. The most common indications for lung resection were infections (n = 17), emphysema (n = 5), lung tumour (n = 2) and others (n = 2). Bronchiectasis (cystic fibrosis or non-cystic fibrosis related) was the main indication for LTx (n = 21), followed by COPD (n = 5). Two patients with a previous pneumonectomy underwent contralateral single LTx and 1 patient with a previous lobectomy had ipsilateral single LTx. The remaining 23 patients underwent bilateral LTx. Clamshell incision was performed in 12 (46%) patients. Moreover, LTx was possible without extracorporeal life support in 13 (50%) patients. 90-Day mortality was 8% (n = 2) and the median survival was 8.7 years. CONCLUSIONS The history of anatomical lung resection is rare in LTx candidates. The majority of patients are young and diagnosed with bronchiectasis. Although the numbers were limited, survival after LTx in patients with previous anatomical lung resection, including pneumonectomy, is comparable to reported conventional LTx for bronchiectasis.

Objective Plication of the diaphragm is a life-changing procedure for patients affected by diaphragm paralysis. Traditionally, this procedure is performed through a thoracotomy. Access to the diaphragm via this incision is poor and the indications for surgery are limited to patients who can actually sustain such an invasive approach and associated morbidities. A minimally invasive approach was developed to improve the surgical management of diaphragm paralysis. Methods Patients underwent minimally invasive diaphragm plication either by video-assisted or robotic surgery through a 3-port technique with CO2 insufflation. Patients were followed at the routine 6-week clinic and also by telephone consultation 6 to 12 months postoperatively. Data were collected on postoperative complications, postoperative pain or numbness, symptomatic improvement, and change to quality of life following surgery. Results Forty-eight patients underwent 49 minimally invasive diaphragm plication. Median postoperative length of hospital stay was 4 days (range: 2 to 34 days) and there were no cases of mortality. Mean reduction in Medical Research Council dyspnea score per patient was 2.2 points (mode: 3 points). Twenty-eight patients (77.8%) reported a significant symptomatic improvement enabling improvements in quality of life, and 97.2% ( n = 35) were satisfied with the surgical outcome. Conclusions Minimally invasive diaphragm plication is a safe procedure associated with prompt postoperative recovery. It is effective at reducing debilitating dyspnea and improving quality of life.

Background Video-assisted thoracoscopic surgery (VATS) lobectomy is currently the recommended approach for treating early-stage non-small cell lung cancer (NSCLC). Different VATS approaches have been proposed so far, and the actual advantages of one technique over the other are still under debate. The aim of our study is to compare postoperative pain and analgesic drug consumption in uniportal VATS and triportal VATS for pulmonary lobectomy in early-stage lung cancer patients. Methods This study is a single-center, prospective, two-arm, parallel-group, randomized controlled trial. It is designed to compare uniportal video-assisted thoracic surgery (u-VATS) and three-port video-assisted thoracic surgery (t-VATS) in terms of postoperative pain. The trial will enroll 120 patients with a 1:1 randomization. The primary outcome is the assessment of analgesic drug consumption. Secondary outcomes are postoperative pain measurement, evaluation of postoperative pulmonary function, and metabolic recovery after pulmonary lobectomy. Discussion The choice of which VATS approach to adopt for treating patients undergoing pulmonary resection mostly depends on the surgeon’s preferences; therefore, it is hard to prove whether one VATS technique is superior to the other. Moreover, postoperative analgesic protocols vary consistently among different centers. To date, only a few studies have evaluated the effects of the most popular VATS techniques. There is no evidence about the difference between multiport VATS and u-VATS in terms of postoperative pain. We hope that the results of our trial will provide valuable information on the outcomes of these different surgical approaches. Trial registration ClinicalTrials.gov NCT03240250. Registered on 07 August 2017; retrospectively registered.

OBJECTIVES The aims of this study were to describe the potential selection criteria for patients scheduled for lobectomy versus segmentectomy for stage I non-small-cell lung cancer and to compare the 2 procedures in terms of intraoperative variables and postoperative outcomes using the European Society of Thoracic Surgeons (ESTS) Registry. METHODS This observational multicentre retrospective cross-sectional study was based on data collected from the ESTS database. The following were set as inclusion criteria: pulmonary lobectomy or segmentectomy for stage I primary lung cancer (according to 8th TNM edition), no previous lung surgery and no induction chemotherapy or radiotherapy. Statistical significance was examined using Mann–Whitney or 2 proportions Z tests. RESULTS Among 63 542 patients enrolled in the ESTS database (2007–2018), 17 692 met the inclusion criteria: 15 845 patients received lobectomy and 1847 segmentectomy. Video-assisted thoracic surgery (VATS) lobectomy and VATS segmentectomy were the 27.8% and 31.9% of the procedures, respectively. Lobectomy group was significantly younger and had a lower American Society of Anaesthesiology (ASA) score, lower comorbidities prevalence and better respiratory function. The segmentectomy group had lower complications rate (25.6% vs 33.8%). When considering only the last 5 years, ASA score was similar between the 2 groups, although pulmonary function remained significantly lower in the segmentectomy group. CONCLUSIONS According to the ESTS database, segmentectomy was preferably offered to ‘compromised’ patients, with limited respiratory function, higher ASA score and relevant comorbidities. Nevertheless, the procedure showed lower complications rate and similar short-term outcomes compared to lobectomy. During the last 5 years, segmentectomy appeared to be regarded as a valid alternative, even for selected patients who could tolerate both procedures.

Highlights • An atypical clinical presentation of early antibody-mediated rejection in COVID era. • The radiological features mimicked SARS-CoV2 pneumonia, but tests were negative. • This is the first report of lung transplantation in the COVID era in Europe. • Decide whether to keep lung transplantation programmes open in a COVID Hospital., Introduction In addition to morbidity and mortality rate per se, COVID-19 outbreak leads to potential ‘side effects’, which are difficult to evaluate and predict. Lung transplantation is a consolidated treatment for end-stage chronic lung disease requiring significantly demanding management. Deciding whether to keep transplant programmes open during an epidemic of this size is not easy, as immunosuppressed subjects face the risk of infection and related mortality. Additionally, there is a chance for the patient’s standard care process to be compromised. Presentation of case We report the case of a patient undergoing bilateral lung transplantation during the explosion of COVID-19 epidemic in Lombardy; he died from definite early acute antibody-mediated rejection, clinically (persistent high fever, unresponsive to treatment) and radiologically mimicking viral pneumonia but persistently negative for SARS-CoV-2. Discussion The diagnosis was difficult given this atypical presentation, confounded by global scenario. Grafts were procured from a donation after circulatory death donor in an uncontrolled setting and a donor-recipient transmission was possible. Our institute became a COVID-Hospital right during the first post-transplantation days. Radiological imaging had the same features of SARS-CoV-2 pneumonia. Conclusions This is the first report of lung transplantation of the COVID-19 era in Europe. Our extremely fragile patient was COVID-19 free up to the end. Donor-recipient transmission is conceivable, but the risk should be assessed with respect to waiting list mortality. Ultimately, treating COVID-19 patients can be a resource-consuming activity but we decided to keep our centre open.

Transbronchial biopsy (TBB) using standard forceps is the main procedure to establish the presence of lung allograft rejection (AR) after lung transplantation. Few studies report the use of the transbronchial cryobiopsy (TCB) as a scheduled procedure for surveillance purposes in lung allograft, despite this the technique yields larger biopsies. We aimed to analyze the diagnostic yield and potential complications of TCB compared with conventional forceps biopsy for acute rejection surveillance in lung transplantation. In our center, TCBs are performed to monitor lung allografts at 3, 6, and 12 months after transplantation. From March 2018 to September 2019 TCBs were performed in 54 lung transplanted patients for surveillance purposes. Clinical and functional data, complications, and histologic results were collected. We analyzed through a retrospective study our first 75 cases of cryobiopsies for surveillance purposes in lung allograft recipients. The diagnostic rate of AR using TCB was 100% compared with 83% using conventional TBB. Also, diagnostic rate of airway inflammation and chronic rejection was 17% and 21% higher, respectively, for TCB compared with TBB. The overall major complication rate was 9%: 1 pneumothorax case required chest tube drainage and 6 moderate bleedings. Bleeding rate in the scheduled TCB group (8%) seems to be higher if compared with scheduled TBB group (1%). TCB seems to be safe and effective for diagnosis of lung AR compared with transbronchial conventional forceps biopsy.

The aim of this study was to assess the impact of BMI on perioperative outcomes in patients undergoing VATS lobectomy or segmentectomy. Data from 5088 patients undergoing VATS lobectomy or segmentectomy, included in the VATS Group Italian Registry, were collected. BMI (kg/m

Background: In rapidly lung deteriorating patients, urgent lung transplantation (ULT) seems the only definitive therapy. Few publications on this topic report conflicting results, putting a word of caution about ULT programs. Methods: A national ULT program was introduced in 2010: patients on mechanical support may be transplanted with the first available graft. We reviewed the experience of three national center, focusing on post-operative outcomes after ULT. Results: Ten patients (17.5%) died awaiting transplantation, while 47 underwent LT with a median urgent waiting list time of 6 days. Pre-operatively, 4.3% of patients were supported only by mechanical ventilation (MV), 55.3% by extracorporeal membrane oxygenation (ECMO) and the remaining 40.4% by both. The main indication was cystic fibrosis (64%). Median recipient lung allocation score was 72. In-hospital mortality was 19%. MV and ECMO median duration of 7 and 3 days, respectively while intensive care unit (ICU) and hospital stay were 20 and 46 days, respectively. At long-term, 1- and 3-year survival rate were 74% and 70%, respectively. Highly impact risk factors for in-hospital mortality were both presence and duration of preoperative veno-arterial ECMO and pre-transplant C-reactive protein level. Conclusions : ULT program allows transplantation in a significant percentage of patients with acceptable results. Pre-operative recipient selection is mandatory to improve clinical outcomes.

There is no unanimity in the literature regarding the value of transbronchial biopsies (TBBs) performed at a scheduled time after lung transplantation (surveillance TBBs [SBs]), compared to biopsies performed for suspected clinical acute rejection (clinically indicated TBBs [CIBs]). This study exposes an assessment of our experience over the last 4 years through a retrospective analysis of the data collected.In our center, SBs are performed at 3, 6, and 12 months after a transplant. Data from 110 patients who underwent a TBB were collected from January 2013 to November 2017. Clinical and functional data along with the histologic results and complications were collected.Overall 251 procedures were performed: 223 for surveillance purposes and 28 for clinical indications. The SBs diagnostic rate was 84%. A grade 2 acute rejection (AR) was detected in 9 asymptomatic patients, all of whom were medically treated, with downgrading of AR documented in all cases. The rate of medical intervention in the SB group was 8%. The CIBs diagnostic rate was 96%. The rate of AR detected by CIBs was significantly higher than by SBs (36% versus 4%; P .0001). Overall the major complication rate was 4%; no patients required transfusions and no mortality occurred in the patient cohort.The surveillance protocol did not eliminate the necessity of CIBs, but in 8% of patients early rejection was histologically assessed. The correlation between histologic and clinical data allows a more careful approach to transplanted patients.

Pleuroparenchymal fibroelastosis (PPFE) is a rare condition, characterized by predominantly upper-lobe pleural and subjacent parenchymal fibrosis, the latter being intra-alveolar with accompanying elastosis of the alveolar walls that leads a clinical progression to respiratory failure. This condition may not be as rare as it seems to be, because nowadays the increasing awareness among specialists is raising the number of new diagnoses. Limited data are available about the prognosis, both for secondary and idiopathic forms. Nevertheless, the idiopathic form seems to be rapidly progressive and no treatment can control the disease, which is why management is challenging. Since the disease was characterized, PPFE cases have been reported in the literature, but most have been secondary rather than idiopathic. Of these, few have successfully undergone lung transplantation as a treatment of end-stage respiratory failure. We here report a successful case of a 38-year-old man affected by idiopathic PPFE who underwent bilateral lung transplantation after extracorporeal membrane oxygenation bridging for an abrupt transition to critical clinical conditions. After a complex postoperative course and a first year characterized by acute rejection, the patient is alive at 5 years with a good quality of life. Our experience confirms that lung transplantation would be a valuable treatment option in case of end-stage idiopathic PPFE cases.

Background Lung transplantation is an established therapeutic option for patients with end-stage pulmonary disease. In May 2005, the lung allocation score (LAS) was introduced in the United States to maximize the benefit to the recipient population and reduce waiting list mortality. The LAS has been applied in a region of Italy since March 2016 on a provisional basis. The aims of the study were describing waiting list characteristics and short-term outcomes after lung transplantation before and after LAS introduction. Methods All the patients who received transplants between January 1, 2011, and March 15, 2017, were included in our retrospective study. The study population was divided into 2 cohorts (historical cohort and post-LAS cohort) and a comparison among the main perioperative data was performed. Results The historical cohort consisted of 415 patients on the waiting list with 91 deaths and 199 lung transplants; the post-LAS cohort consisted of 134 patients with 10 deaths on the waiting list and 51 transplants. Median waiting time and mortality on the list decreased from 223 to 106 days (P = .03) and from 11.2% to 7.5% (P > .05), respectively. The transplantation rate increased from 25% to 38% (P = .001) and the probability to receive a transplant in the first year in the post-LAS era increased significantly (P = .004). Conclusions The results of the introduction of the LAS system in our region are encouraging and have not shown any adverse short-term effects. The regional coordination decided to prolong the experimental application of LAS in order to accumulate more data and to evaluate medium-term outcomes.

Background Solid organ transplantation is associated with a higher risk of Epstein-Barr virus (EBV)–related lymphoproliferative disease due to immunosuppressive regimen. Little evidence is currently available on post-transplant lymphoproliferative disorders (PTLDs) in the lung transplant (LuTx) setting, particularly in cystic fibrosis (CF) recipients. Methods We retrospectively analyzed all the cases of PTLDs that occurred in our LuTx center between January 2015 and December 2017. We reviewed clinical and radiologic data, donor and recipient EBV serostatus, immunosuppressive therapy, histologic data, and follow-up of these patients. Results A total of 77 LuTxs were performed at our center in the study period; 39 (50.6%) patients had CF; 4 developed EBV-related PTLDs. They were all young (17–26 years) CF patients with high serum EBV DNA load. Disease onset was within the first 3 months after LuTx. In 3 cases presentation was associated with fever and infection-like symptoms, whereas in 1 case radiologic suspicion arose unexpectedly from a CT scan performed for different clinical reasons. Diagnosis was reached through lung biopsy in all cases. All patients received rituximab, cyclophosphamide, doxorubicin hydrochloride (hydroxydaunomycin), vincristine sulfate (Oncovin), and prednisone with variable response and complications. Conclusion In our experience, the early development of EBV-related PTLD was a highly aggressive, life-threatening condition, which exclusively affected young CF patients in the early post-transplant period. The rate of this complication was relatively high in our population. Diagnosis with lung biopsy is crucial in all suspected cases and regular monitoring of EBV DNA levels is of utmost importance given the high correlation with PTLDs in patients at increased risk.

Objective For small-sized recipients of lung transplantation, the time span for organ reception from standard donors is generally longer than for normal-sized patients. Despite its underuse, lobar reduction may be a concrete option for these patients. This study aims to assess early and long-term outcomes associated with lobar reduction in lung transplantation. Methods A retrospective study was performed on 608 consecutive lung transplantations at 2 centers between January 2005 and August 2019 (559 standard lung transplantations [standard transplantation] and 49 with lobar reduction [lung transplantation group]). A propensity-score weighting approach was used to account for potential confounding related to patients' nonrandom allocation to the 2 intervention groups. The effects of the intervention on postoperative outcomes were assessed with a weighted regression approach. Results The propensity score was estimated on 571 patients (522 in standard transplantation group and 49 in lung transplantation group). In terms of early outcomes, the lung transplantation group showed a higher percentage of severe primary graft dysfunction at 0 hours and reported longer intensive care unit stay than the standard transplantation group. No other differences in terms of morbidity, mortality, mechanical ventilation time, hospital stay, and anastomotic complications were observed. Although the lung transplantation group showed worse long-term pulmonary function, the 2 populations had comparable survival outcomes. Conclusions The use of lobar reduction showed early and long-term results comparable to those after standard lung transplantation. Although a higher rate of early severe primary graft dysfunction and slightly reduced respiratory function were detected in the lobar group, these did not affect patients' morbidity and survival.

Summary Background Lung transplantation is a life-saving treatment for patients with end-stage lung disease; however, it is infrequently considered for patients with acute respiratory distress syndrome (ARDS) attributable to infectious causes. We aimed to describe the course of disease and early post-transplantation outcomes in critically ill patients with COVID-19 who failed to show lung recovery despite optimal medical management and were deemed to be at imminent risk of dying due to pulmonary complications. Methods We established a multi-institutional case series that included the first consecutive transplants for severe COVID-19-associated ARDS known to us in the USA, Italy, Austria, and India. De-identified data from participating centres—including information relating to patient demographics and pre-COVID-19 characteristics, pretransplantation disease course, perioperative challenges, pathology of explanted lungs, and post-transplantation outcomes—were collected by Northwestern University (Chicago, IL, USA) and analysed. Findings Between May 1 and Sept 30, 2020, 12 patients with COVID-19-associated ARDS underwent bilateral lung transplantation at six high-volume transplant centres in the USA (eight recipients at three centres), Italy (two recipients at one centre), Austria (one recipient), and India (one recipient). The median age of recipients was 48 years (IQR 41–51); three of the 12 patients were female. Chest imaging before transplantation showed severe lung damage that did not improve despite prolonged mechanical ventilation and extracorporeal membrane oxygenation. The lung transplant procedure was technically challenging, with severe pleural adhesions, hilar lymphadenopathy, and increased intraoperative transfusion requirements. Pathology of the explanted lungs showed extensive, ongoing acute lung injury with features of lung fibrosis. There was no recurrence of SARS-CoV-2 in the allografts. All patients with COVID-19 could be weaned off extracorporeal support and showed short-term survival similar to that of transplant recipients without COVID-19. Interpretation The findings from our report show that lung transplantation is the only option for survival in some patients with severe, unresolving COVID-19-associated ARDS, and that the procedure can be done successfully, with good early post-transplantation outcomes, in carefully selected patients. Funding National Institutes of Health. Video Abstract Early outcomes after lung transplantation for severe COVID-19

Extracorporeal membrane oxygenation (ECMO) bridge to lung transplantation (LuTX) exposes the patients to a high risk of perioperative bleeding secondary to systemic anticoagulation and coagulation factors deficiency. With this case series, we propose innovative "no-heparin" management of ECMO-bridge support during LuTX, based upon 1) control heparin resistance with antithrombin III in the preoperative period; 2) relying upon a fully functional, brand new heparinized ECMO circuit; 3) completely avoiding perioperative heparin; 4) hampering fibrinolysis with tranexamic acid; and 5) limiting venoarterial (VA) ECMO escalation, and the following need for full anticoagulation. Following the application of this new approach, we carried out three challenging clinical cases of bilateral ECMO-bridged LuTX effectively, with limited intraoperative blood requirement and no major postoperative bleeding or thromboembolic events. Of note, two of them had an extremely high risk for hemorrhage due to complete right lung anatomic derangement in case number 2 and surgical adhesion following first LuTX in case number 3, while for the case number 1, no blood products were administered during surgery. Despite the limited patient population, such an approach relies on a strong rationale and may be beneficial for managing ECMO bridging to LuTX. Prospective studies are necessary to confirm the validity of our strategy.

Thoracoscopic lobectomy (VATS-L) for non-small-cell lung cancer (NSCLC) is a well-established option for early stage NSCLC, but the evidences are limited for octogenarians.The objectives of this multi-institutional study were to evaluate the post-operative outcomes of VATS-L in octogenarians and to estimate the post-operative quality of life (QoL) using a validated questionnaire (EuroQoL5D).Data from patients underwent VATS-L between 2014 and 2019 were analysed and divided into two groups: Group A (younger patients) and Group B (octogenarians). To define predictors for complications, univariate and multivariable logistic regression analysis were performed.7023 patients underwent VATS-L and 329 (4.6%) were octogenarians. 30-day and 90-day post-operative mortality were similar (0.95% vs 0.91%, p = 0.84 and 1.3% vs 1.2%, p = 0.58), whereas the percentage of patients who suffered from any complication (25.5% vs 31.9%, p = 0.012) and the complication rate (31.6% vs 45.2%, p=0.01) were higher for octogenarians. At discharge, the values of EuroQoL5D were worse in group B, but after one month these levels became similar. Age80 years had a significant influence on morbidity on both univariate and multivariable analyses (p = 0.025).VATS-L for NSCLC can be performed in selected octogenarians without increased risk of post-operative death, acceptable not-life-threatening complications and a moderate impact on QoL.

OBJECTIVES Resection of thymic tumours including the removal of both the tumour and the thymus gland (thymothymectomy; TT) is the procedure of choice and is recommended in most relevant articles in the literature. Nevertheless, in recent years, some authors have suggested that resection of the tumour (simple thymomectomy; ST) may suffice from an oncological standpoint in patients with early-stage thymoma who do not have myasthenia gravis (MG) (non-MG). The goal of our study was to compare the short- and long-term outcomes of ST versus TT in non-MG early-stage thymomas using the European Society of Thoracic Surgeons thymic database. METHODS A total of 498 non-MG patients with pathological stage I thymoma were included in the study. TT was performed in 466 (93.6%) of 498 patients who had surgery with curative intent; ST was done in 32 (6.4%). The completeness of resection, the rate of complications, the 30-day mortality, the overall recurrence and the freedom from recurrence were compared. We performed crude and propensity score-adjusted comparisons by surgical approach (ST vs TT). RESULTS TT showed the same rate of postoperative complications, 30-day mortality and postoperative length of stay as ST. The 5-year overall survival rate was 89% in the TT group and 55% in the ST group. The 5-year freedom from recurrence was 96% in the TT group and 79% in the ST group. CONCLUSION Patients with early-stage thymoma without MG who have a TT show significantly better freedom from recurrence than those who have an ST, without an increase in postoperative morbidity rate.

Korrektur zu 10.1093/ejcts/ezab224

Background The usefulness of digital chest drain is still debated. We are carrying out a study to determine if the use of a digital system compared with a traditional system reduces the duration of chest drainage. To evaluate safety, benefit, or futility of this trial we planned the current interim analysis. Methods An interim analysis on preliminary data from ongoing investigator-initiated, multicenter, interventional, prospective randomized trial. Original protocol number: (NCT03536130). The interim main endpoint was overall complications; secondary endpoints were the concordance between the two primary endpoints of the RCT (chest tube duration and length of hospital stay). We planned the interim analysis when half of the patients have been randomised and completed the study. Data were described using mean and standard deviation or absolute frequencies and percentage. T-test for unpaired samples, Chi-square test, Poisson regression and absolute standardized mean difference (ASMD) were used. P-value Results From April 2017 to November 2018, out of 317 patients enrolled by 3 centers, 231 fulfilled inclusion criteria and were randomized. Twenty-two of them dropped out after randomization. Finally, 209 patients were analyzed: among them 94 used the digital device and 115 the traditional one. The overall postoperative complications were 35 (16.8%) including prolonged air leak (1.9%). Mean chest tube duration was 3.6 days (SD = 1.8), with no differences between two groups (p = 0.203). The overall difference between hospital stay and chest tube duration was 1.4 days (SD = 1.4). Air leak at first postoperative day detected by digital and traditional devices predicted increasing in tube duration of 1.6 day (CI 95% 0.8–2.5, p p Conclusions This interim analysis supported the authors’ will to continue with the enrollment and to analyze data once the estimated sample size will be reached. Trial registration Trial registration number NCT03536130, Registered 24 May 2018 - Retrospectively registered.

Introduction Gastroesophageal reflux disease (GERD) is frequently seen in patients with systemic sclerosis (SSc). Long-standing GERD may cause esophagitis, long-segment strictures, and Barrett’s esophagus and may worsen pre-existing pulmonary fibrosis with an increased risk of end-stage lung disease. Surgical treatment of recalcitrant GERD remains controversial. The purpose of this systematic review was to summarize the current data on surgical treatment of recalcitrant GERD in SSc patients. Materials and methods A systematic literature review according to PRISMA and MOOSE guidelines. PubMed, EMBASE, and Web of Science databases were consulted. Results A total of 101 patients were included from 7 studies. The age ranged from 34 to 61 years and the majority were females (73.5%). Commonly reported symptoms were heartburn (92%), regurgitation (77%), and dysphagia (74%). Concurrent pulmonary disease was diagnosed in 58% of patients. Overall, 63 patients (62.4%) underwent open fundoplication, 17 (16.8%) laparoscopic fundoplication, 15 (14.9%) Roux en-Y gastric bypass (RYGB), and 6 (5.9%) esophagectomy. The postoperative follow-up ranged from 12 to 65 months. Recurrent symptoms were described in up to 70% and 30% of patients undergoing fundoplication and RYGB, respectively. Various symptoms were reported postoperatively depending on the type of surgical procedures, anatomy of the valve, need for esophageal lengthening, and follow-up. Conclusions The treatment of recalcitrant GERD in SSc patients is challenging. Esophagectomy should be reserved to selected patients. Minimally invasive RYGB appears feasible and safe with promising preliminary short-term results. Current evidence is scarce while a definitive indication about the most appropriate surgical treatment is lacking.

OBJECTIVES The European Society of Thoracic Surgeons Lung Transplantation Working Group promoted a survey to evaluate overall survival in a large cohort of patients receiving lung transplants for rare pulmonary diseases. METHODS We conducted a retrospective multicentre study. The primary end point was overall survival; secondary end points were survival of patients with the most common diagnoses in the context of rare pulmonary diseases and chronic lung allograft dysfunction (CLAD)-free survival. Finally, we analysed risk factors for overall survival and CLAD-free survival. RESULTS Clinical records of 674 patients were extracted and collected from 13 lung transplant centres; diagnoses included 46 rare pulmonary diseases. Patients were followed for a median of 3.1 years. The median survival after a lung transplant was 8.5 years. The median CLAD-free survival was 8 years. The multivariable analysis for mortality identified CLAD as a strong negative predictor [hazard ratio (HR) 6.73)], whereas induction therapy was a protective factor (HR 0.68). The multivariable analysis for CLAD occurrence identified induction therapy as a protective factor (HR 0.51). When we stratified patients by CLAD occurrence in a Kaplan–Meier plot, the survival curves diverged significantly (log-rank test: P CONCLUSIONS We observed that overall survival and CLAD-free survival were excellent. We support the practice of allocating lungs to patients with rare pulmonary diseases because a lung transplant is both effective and ethically acceptable.

Background Although minimally invasive lobectomy has gained worldwide interest, there has been debate on perioperative and oncological outcomes. The purpose of this study was to compare outcomes among open lobectomy, video-assisted thoracic surgery lobectomy, and robotic lobectomy. Methods PubMed, EMBASE, and Web of Science databases were consulted. A fully Bayesian network meta-analysis was performed. Results Thirty-four studies (183,426 patients) were included; 88,865 (48.4%) underwent open lobectomy, 79,171 (43.2%) video-assisted thoracic surgery lobectomy, and 15,390 (8.4%) robotic lobectomy. Compared with open lobectomy, video-assisted thoracic surgery, lobectomy and robotic lobectomy had significantly reduced 30-day mortality (risk ratio = 0.53; 95% credible intervals, 0.40–0.66 and risk ratio = 0.51; 95% credible intervals, 0.36–0.71), pulmonary complications (risk ratio = 0.70; 95% credible intervals, 0.51–0.92 and risk ratio = 0.69; 95% credible intervals, 0.51–0.88), and overall complications (risk ratio = 0.77; 95% credible intervals, 0.68–0.85 and risk ratio = 0.79; 95% credible intervals, 0.67–0.91). Compared with video-assisted thoracic surgery lobectomy, open lobectomy, and robotic lobectomy had a significantly higher total number of harvested lymph nodes (mean difference = 1.46; 95% credible intervals, 0.30, 2.64 and mean difference = 2.18; 95% credible intervals, 0.52–3.92) and lymph nodes stations (mean difference = 0.37; 95% credible intervals, 0.08–0.65 and mean difference = 0.93; 95% credible intervals, 0.47–1.40). Positive resection margin and 5-year overall survival were similar across treatments. Intraoperative blood loss, postoperative transfusion, hospital length of stay, and 30-day readmission were significantly reduced for minimally invasive approaches. Conclusion Compared with open lobectomy, video-assisted thoracic surgery lobectomy, and robotic lobectomy seem safer with reduced 30-day mortality, pulmonary, and overall complications with equivalent oncologic outcomes and 5-year overall survival. Minimally invasive techniques may improve outcomes and surgeons should be encouraged, when feasible, to adopt video-assisted thoracic surgery lobectomy, or robotic lobectomy in the treatment of lung cancer.

Knowledge of preoperative right heart function of adult patients with cystic fibrosis (CF) awaiting lung transplant (LUTX) is limited. The echocardiography of adult patients with CF enlisted for LUTX was retrospectively analyzed and compared with standards and invasive analyses (right heart catheterization, multigated radionuclide ventriculography). We included 49 patients (reported as mean ± standard deviation; 29 ± 9 years of age; forced expiratory volume in first second of expiration, 31% ± 11% predicted; lung allocation score, 36 ± 5; invasive mean pulmonary artery pressure, 17 ± 5 mm Hg; multigated radionuclide ventriculography right ventricle [RV] ejection fraction, 50% ± 9%). Patients had increased RV end-diastolic area, RV wall thickness, and increased pulmonary artery acceleration time with subnormal tricuspid annular plane systolic excursion, tissue Doppler positive peak systolic velocity, and fraction area change. Subnormal tricuspid annular plane systolic excursion (23 mm), tissue Doppler positive peak systolic velocity (14 cm/s), and fraction area change (49%) had high sensitivity and negative predictive value in predicting impaired RV. EJECTION FRACTION: A good correlation between echocardiographic estimated and invasively measured systolic pulmonary artery pressure was observed (R

OBJECTIVES Risk factors for pneumothorax recurrence after videothoracoscopy for primary spontaneous pneumothorax are still being debated. The goal of this study was to assess whether the pleurodesis technique and other variables are possibly associated with the postoperative ipsilateral recurrence of pneumothorax. METHODS We retrospectively collected data of 1178 consecutive ≤40-year-old patients who underwent videothoracoscopy for primary spontaneous pneumothorax in 9 centres between 2007 and 2017. We excluded patients with hybrid pleurodesis and/or incomplete follow-up, leaving for analysis 843 cases [80% men; median age (interquartile range) 22 (18–28) years]. Univariable and multivariable analyses were performed by logistic regression and tested by Cox regression model to assess factors related to ipsilateral pneumothorax recurrence including age, gender, body mass index, smoking habit, cannabis smoking, respiratory comorbidity, dystrophic severity score, surgical indication, videothoracoscopy port number and side, lung resection, pleurodesis technique and postoperative prolonged air leak (>5 days). RESULTS Blebs/bullae resection was performed in 664 (79%) patients. Pleurodesis was achieved by partial pleurectomy in 228 (27%) cases; by pleural electrocauterization in 176 (21%); by pleural abrasion in 121 (14%); and by talc poudrage in 318 (38%). During a median follow-up period of 70.0 months (95% confidence interval 66.6–73.4), pneumothorax recurred in 79 patients (9.4%); among these, 29 underwent redo surgery; 34, chest drain/talc slurry; and 16, clinicoradiological observation. The only independent risk factor for recurrence was postoperative prolonged air leak (P CONCLUSIONS In this multicentric series, postoperative ipsilateral pneumothorax recurrence was remarkable and independently related to prolonged postoperative air leak; besides the retrospective study setting, the pleurodesis method did not have an impact on recurrence. To prevent prolonged air leak, blebs/bullae treatment should be accurate and performed only if indicated.

Validation of predictive risk models for prolonged air leak (PAL) is essential to understand if they can help to reduce its incidence and complications. This study aimed to evaluate both the clinical and statistical performances of 4 existing models. We selected 4 predictive PAL risk models based on their scientific relevance. We referred to these models as Chicago, Bordeaux, Leeds and Pittsburgh model, respectively, according to the affiliation place of the first author. These predicting risk models were retrospectively applied to patients recorded on the second edition of the Italian Video-Assisted Thoracoscopic Surgery Group registry. Predictions for each patient were calculated based on the logistic regression coefficient values provided in the original manuscripts. All models were tested for their overall performance, discrimination, and calibration. We recalibrated the original models with the re-estimation of the model intercept and slope. We used curve decision analysis to describe and compare the clinical effects of the studied risk models. Better statistical metrics characterize the models developed on larger populations (Chicago and Bordeaux models). However, no model has a valid benefit for threshold probability greater than 0.30. The Net benefit of the most performing model (Bordeaux model) at the threshold probability of 0.11 is 23 of 1000 patients, burdened by 333 false positive cases. One of 1000 is the Net benefit at the threshold probability of 0.3. The use of PAL scores based on preoperative predictive factors cannot be currently used in a clinical setting because of a high false positive rate and low positive predictive value.

BACKGROUND Lung transplantation is a complex but effective treatment of end-stage pulmonary disease. Among the post-operative complications, phrenic nerve injury, and consequent diaphragmatic dysfunction are known to occur but are hitherto poorly described. We aimed to investigate the effect of lung transplantation on diaphragmatic function with a multimodal approach. METHODS A total of 30 patients were studied at 4 time points: pre-operatively, at discharge after surgery, and after approximately 6 and subsequently 12 months post surgery. The diaphragmatic function was studied in terms of geometry (assessed by the radius of the diaphragmatic curvature delineated on chest X-ray), weakness (considering changes in forced vital capacity when the patient shifted from upright to supine position), force (maximal pressure during sniff), mobility (excursion of the dome of the diaphragm delineated by ultrasound), contractility (thickening fraction assessed by ultrasound), electrical activity (latency and area of compound muscle action potential during electrical stimulation of phrenic nerve), and kinematics (relative contribution of the abdominal compartment to tidal volume). RESULTS Despite good clinical recovery (indicated by spirometry and 6 minutes walking test), a reduction of the diaphragmatic function was detected at discharge; it persisted 6 months later to recover fully 1 year after transplantation. Diaphragmatic dysfunction was demonstrated in terms of force, weakness, electrical activity, and kinematics. Our data suggest that the dysfunction was caused by phrenic nerve neurapraxia or moderate axonotmesis, potentially as a consequence of the surgical procedure (i.e., the use of ice and pericardium manipulation). CONCLUSIONS The occurrence of diaphragmatic dysfunction in patients with a good clinical recovery indicates that the evaluation of diaphragmatic function should be included in the post-operative assessment after lung transplantation.

Objectives A project to assess the existing literature and the quality of past guidelines on the management of primary spontaneous pneumothorax was developed by the Italian Society of Thoracic Surgeons, with particular focus on the assessment of the methods used to produce such recommendations. Methods The different items and domains within each guideline were assessed using the Appraisal of Guidelines for Research and Evaluation (AGREE) II instrument and scored on a 7-point scale. Results Five guidelines matched the inclusion criteria and were assessed. A multinational collaboration produced 2 of 5 guidelines. The observers recommended (with modifications) only 2 guidelines. Clarity of presentation, scope and purpose (objectives and health questions target the population) received the best score, whereas the applicability of the guideline received the lowest score. International development positively influenced the scope and purpose of the guidelines. Moreover, improved scores were achieved when the stakeholders were fully involved and had editorial independence. Conclusions As assessed by the AGREE II criteria, the quality of the various guidelines was extremely inconsistent. Guidelines with higher AGREE II scores were those developed with the participation of European scientific societies.

Lung transplantation is a limited by donor pool shortage. Despite the efforts to extend the graft acceptability with recurrent donor criteria reformulations, previous cardiothoracic surgery is still considered a contraindication. A donor who underwent cardiac surgery could potentially provide an ideal lung but high intraoperative risks and intrinsic technical challenges are expected during the graft harvesting. The purpose of this study is to present our dedicated protocol and four clinical cases of successful lung procurements from donors who had a previous major cardiac surgery. One donor had ascending aortic root (AAR) substitution, another had mitral valve substitution, and two had coronary artery bypass surgery. The others' eligibility criteria for organ allocation, such as ABO compatibility, PaO2/FiO2 ratio, absence of aspiration, or sepsis were respected. In one of the cases with previous coronary bypass grafting, the donor had a veno-arterial extracorporeal membrane oxygenation support. Consequently, the grafts required an ex vivo lung perfusion evaluation. We report the technical details of procurement and postoperative courses of recipients. All procurements were uneventful, without lung damage or waste of abdominal organs related to catastrophic intraoperative events. All recipients had a successful clinical outcome. We believe that successful transplantation is achievable even in a complicated setting, such as cases involving donors with previous cardiac surgery frequently are. Facing lung donor shortage, we strongly support any effort to avoid the loss of possible acceptable lungs. In particular, previous major cardiac surgery does not strictly imply a poor quality of lungs as well as unsustainable graft procurement.

Introduction Lung transplantation is considered a therapeutic option in selected patients affected by end-stage pulmonary disease. The mortality on the waiting list is mainly attributed to the shortage of the donor pool available for transplantation. There are various strategies to overcome this shortage; one of them is lobar transplantation. Methods The aim of the current study was to analyze the outcome of lobar lung transplantation from deceased donors in our Lung Transplant Center. Overall survival, perioperative mortality and morbidity, problem on bronchial anastomosis, and chronic rejection were prospectively recorded in a 5-year time-frame. Results From November 2010 to October 2015, we performed 100 lung transplantations; 6 of which (6%) were lobar transplantations from deceased donors. Three recipients were on an emergency list due to preoperative extracorporeal support. The causes of lobectomy leading to lobar transplantation were: size mismatch (3), iatrogenic vascular damage (2), and chronic atelectasis (1). One patient died 5 months after surgery for sepsis; and 5 patients were alive at the study end (median follow-up: 17.5 months). Prevalence of grade 3 primary graft dysfunction at 72 hours was 50%. One patient developed bronchial stenosis. No cases of chronic rejection were recorded. Conclusions Lobar transplantation can be considered a valid tool to overcome the donor pool shortage in selected cases; such a technique has proved particularly useful in critically ill patients who were scheduled in an emergency transplant program.

Purpose Transbronchial biopsy (TBB) using forceps is the standard procedure to establish the presence of allograft rejection after lung transplantation. However, inadequate tissue samples, high degree of interobservers variability and possible complications seems to prevent many centers in scheduling TBB in lung transplant follow-up. Despite transbronchial cryobiopsies (TCB) yield large specimens, few studies addressed the use of this technique. We aimed to analyze the diagnostic yield and complications rate of TCB in a surveillance program for lung transplant patients. Methods This is a retrospective comparative study with historical control. Eligible for inclusion were adults subjected to scheduled transbronchial biopsy at 3, 6 and 12 months after lung transplantation. A single pathologist classified the biopsy according to ISHLT scale. Results From 2018, 54 consecutive patients underwent TCB; previous 110 consecutive patients underwent TBB. The study group received 75 procedures versus 223 in the historical group. The diagnostic yield for acute rejection of TCB and TBB were 100% and 83%, respectively (p Conclusion TCB showed high diagnostic yield in a surveillance program for lung transplant patients; despite the low clinical impact, the complication rate is not negligible. These good results have led us to implement an interventional crossover trial on TCB versus TBB.

Purpose Lung transplantation (LT) usually requires an optimal donor/recipient size matching to guarantee satisfactory results. In patients of small dimensions or with reduced thoracic cage the waiting time to receive a standard organ may be greater than their life expectancy. Lobar reduction is an important surgical option for these subjects but it is so far underutilized. In addition, lobar transplantation is suspected of high perioperative complications being technically demanding. This bicentric cohort study analyzed the impact of lobar lung transplantation on 1-year survival. Secondary end-point were common early and long-terms outcomes. Methods A retrospective study was performed on 619 consecutive LT between January 2006 and December 2018 (559 standard LT, group I and 60 lobar reduction, group II). A propensity score weighting approach was employed to account for potential confounding factors. The effect of the intervention on the post-operative outcomes of interest was assessed using a weighted regression approach. Results The propensity score was estimated on 571 patients (522 in group I and 49 in group II). Group I presented a higher percentage of single LT (29% vs 4%, p Considering early outcomes, group II presented a higher percentage of severe PGD (2-3) at 72 hours (52 vs 35%, p=0.022) and longer ICU stay (9 vs 6 days, p=0.014) compared to group I. No other differences in terms of morbidity, mortality, mechanical ventilation and hospital stay were observed. At long-terms, the two groups presented comparable 5-year survival (51 vs 57%) and pulmonary function (best post-operative percentage FEV1, 84 vs 78%). At the regression analysis, lobar lung transplantation was associated with severe PGD at 72 hours (p=0.01) and worse long-term pulmonary function (p=0.04). Conclusion In our cohort, lobar transplantation did not affect 1-year survival. Although a higher rate of severe PGD at 72 hours and a slightly reduced respiratory function were observed in the lobar transplantation group, these factors did not affect the morbidity and long-term survival. Lobar transplantation could be positively considered to increase the donors’ pool especially for recipients with small chest cavity.

Background and aim: Liver transplantation (LT) is a validated treatment for hepatocellular carcinoma (HCC). HCC recurrence occurred between 8 and 20% of patients and lung is the most frequent site. Pulmonary metastases resection (PMR) prolongs survival, however in LT-setting the impact on survival is unclear. To give new lights on this issue, we report the experience of three Italian LT Centers. Methods: All consecutive HCC transplanted patients in three Italian LT Centers, who developed pulmonary metastasis from HCC (PM-HCC), as first metastasis, from 2008 to 2018, were included whenever treated with PMR. Results: Twenty-five patients were enrolled (median age 58 yrs, 84% male, 3% cirrhotics). HCC recurred after 34 months (9–306) since LT and PMR was performed after 2.4 months (0–43.1). A total of 28 PMR (19 single resections; 9 multiple resections; 16 right; 2 left) have been performed on 24 patients while in one case percutaneous microwave ablation (MWA) was preferred. Four patients have been re-operated due to pulmonary HCC-recurrence after surgery. The majority of surgical resection type was wedge resection (26, 89%). Surgical access was: video-assisted thoracic surgery (VATS) in 17 cases (59%); thoracotomy in 11 (38%); MWA in 1 (3%). The 48% of nodule was in right lower lobe. Perioperative in-hospital mortality and 30 days mortality were nil; median surgical time 90 min (50–365); median post-operative overall stay 5 days (2–11). Post-operative ICU treatment was necessary in 1 case (3%) for 3 days; blood transfusions in 2 cases (7%). Overall, 5 complications (2 bleeding; 1 AKI; 1 major cardiac; 1 wound dehiscence) occurred, with an overall complications rate of 23%. Eight (32%) patients died during a follow-up after HCC recurrence of 32 months (7–213): 7 for HCC progression, 1 for severe liver failure due to chronic rejection. The 1 and 5 year cumulative probability of OS from recurrence were 100 and 43% (95%CI 12–74), respectively, with a median OS of 51 months (95%CI 24–78). Conclusion: Selected patients with isolated pulmonary HCC-recurrence after LT and with preserved hepatic function showed that a pulmonary metastasectomy could be efficacious in managing a PM-HCC and could give an opportunity for long-term survival.

Background Predictors and outcomes of intraoperative extracorporeal membrane oxygenation (ECMO) during lung transplantation (LUTX) for cystic fibrosis (CF) are unknown. Methods We retrospectively collected the clinical data at enlistment of the CF patients who underwent double LUTX from January 2013 to December 2018 at an Italian tertiary referral center. We compared blood transfusions, incidence of primary graft dysfunction (PGD), duration of mechanical ventilation, intensive care unit (ICU) length of stay (LOS), hospital LOS and survival of ECMO and non-ECMO patients. Chi-square, Kruskal-Wallis, and log-rank tests were used. Results Twenty-eight (40%) of the 70 included patients needed intraoperative central veno-arterial ECMO with postoperative veno-venous prolongation in 6 subjects. Lower right ventricle ejection fraction (p = 0.013, OR 0.92(0.86–0.98)), higher oxygen requirement (p = 0.026, OR 1.39(1.01–1.90)), lower body surface area (p = 0.044, OR 0.05(0.00–1.03)), and CF-related diabetes (p = 0.044, OR 2.81(1.03–7.66)) were associated with intraoperative ECMO. Compared to non-ECMO patients, ECMO patients needed almost fivefold intraoperative transfusion (2227 mL vs. 570 mL, p 0 at 72 h more frequently (16/57% vs. 12/28%, p = 0.017, OR 3.33(1.22–9.09)). Mechanical ventilation, ICU LOS and hospital LOS were significantly longer in ECMO patients. Survival at follow-up (651(326–1277) days) of ECMO and non-ECMO patients was 78% vs. 83%, respectively (OR 0.73 (0.21–2.46), p = 0.616, log-rank test p = 0.498). Conclusion : Pre-operative risk assessment and clinical planning should be done according to the predictors above. While undeniably useful as a life-saving procedure, ECMO during LUTX for CF is associated with worsened short-term outcomes. ECMO should be implemented weighing its risk and benefits.

Hepatocellular carcinoma (HCC) recurring after liver transplantation (LT) is a major clinical concern, occurring in up to 20% and being the most frequent cause of death in this setting. Usually recurrence occurs within the first 2 years, whereas late and very late recurrences are rare. We report a 71-year-old woman with HCC recurrence after 25 years from LT, an event never reported before. Diagnosis was achieved with a progressive increase of alpha-fetoprotein (AFP) followed by a computed tomography scan, showing a mediastinal, upper diaphragmatic, right paracaval mass of 5 cm in size. The lesion was treated with a surgical approach involving a multidisciplinary team including hepatobiliary, thoracic, and cardiovascular surgeons. A sternotomy and mass removal was performed without the need of an extracorporeal bypass. A complete resection of the tumor was achieved, with a drop in AFP and without signs of recurrence after 1-year follow up. In conclusion, the possibility of late HCC recurrences after LT, despite being rare, underlines the need of a standardized, cost-benefit, optimal strategy of a long-term surveillance. From a surgical point of view, our case is unusual for the site and the character of the lesion, and for the absence of the need of an extracorporeal bypass during the operation.

Objectives Vascular injuries are among the most severe causes of unplanned conversion during VATS lobectomies. The study aimed to analyse the incidence of vascular injuries and their risk factors during VATS lobectomy. Methods The Italian VATS lobectomy Registry was used to collect data from 66 Thoracic Surgery Units. From 2013 to October 2016 (out of more than 3,700 patients enrolled) only information from Units with an enrollment >100 VATS lobectomies were retrospectively analysed. Logistic regression analysis was performed on selected variables of the univariate analysis. Results Ten institutions contributed a total of 1,679 patients. Vascular injuries leading to conversion occurred in 44 (2.6%) patients. Years of experiences were inversely related to the risk of vascular injuries. Univariate analysis showed age, gender, surgical activity, Charlson Index Score and number of resected lymph nodes like significantly associated variables. Multivariate analysis revealed that number of resected lymph nodes, VATS experience ratio (number of VATS lobectomies/total lobectomies performed in the same year at same centre), and surgical activity of the centre were significantly associated with the risk of conversion. Unplanned thoracotomy was correlated with postoperative morbidity. Conclusion Vascular injuries in VATS lobectomies represented a rare complication which could directly affect the postoperative outcomes. The predictive factors for conversion were multifactorial and depended on characteristics of centres and surgeons’ seniority. Minimally invasive VATS lobectomy approaches did not influence the risk of vascular damages.

OBJECTIVES Donation after circulatory death (DCD) potentially provides transplantable lungs suitable for a transplant, but in Italy, the need for 20 min of a no-touch period after cardiac arrest for legal declaration of death poses real challenges to organ preservation. METHODS This is a single-institution, retrospective study using data collected prospectively between October and December 2017. After the approval of the multidisciplinary DCD study group of Regione Lombardia, Maastricht category III DCD donors became eligible for combined procurement of lungs and abdominal organs. Our group subsequently established a dedicated technical protocol. Our protocol consists of a non-rapid normothermic open-lung procurement process that takes place during abdominal normothermic regional perfusion, namely without pleural topical cooling before the start of pneumoplegia. After the lung is procured according to the technique described in the article, lung function is evaluated by ex vivo lung perfusion, which is run with the low-flow, open atrium, low haematocrit technique. RESULTS During the study, we managed 5 controlled DCDs. In 3 cases, the lungs were successfully transplanted. All 3 patients are alive after 1 year, with good respiratory function. CONCLUSIONS Our approach resulted in adequate lung preservation and successful transplants without detrimental effects on abdominal organ procurement, confirming the possibility of overcoming the obstacle of a long no-touch period in a DCD setting.

Purpose Transbronchial biopsy (TBB) using forceps is the standard procedure to establish the presence of allograft rejection after lung transplantation. However, inadequate tissue samples, high degree of interobservers variability and possible complications seems to prevent many centers in scheduling TBB in lung transplant follow-up.We aimed to compare histological quality of cryobiopsy (CB) and conventional forceps biopsy (FB) for sampling lung tissue in transplants recipients. Methods Eligible for inclusion were adults subjected to scheduled transbronchial biopsy at 3, 6 and 12 months after lung transplantation. A single pathologist classified the biopsy according to ISHLT scale.From January 2019 to August 2020, 54 consecutive transbronchial lung biopsies procedures were included in the study. All patients underwent at least 6 biopsies with forceps and 3 with cryoprobe in the same lung lobe. Clinical, functional data and histological findings were collected. Results The diagnostic yield of acute rejection using cryobiopsy is 100% compared to 79% using biopsy forceps. The difference in proportion is 0.20 [95% C.I: 0,11-0,29, p Conclusion Transbronchial cryobiopsy is effective for diagnosis of lung allograft rejection because it provides larger and more diagnostic lung parenchyma specimens than traditional forceps biopsies.

Purpose The outcome of lung transplantion (LuTx) suffers from a high rejection rate, and there are still huge gaps of knowledge about immune-mediated rejection mechanisms. Acute rejection (AR) can lead to chronic lung allograft dysfunction (CLAD), the main cause of poor survival and low quality of life. The standardized morphologic evaluation of rejection is based on histopathologic diagnostic criteria at a given time-point, but it has a limited prognostic value towards clinical outcome and the likelihood to develop CLAD. We analyzed immune-check point proteins in lung tissues of patients who received a LuTx and who were or were not undergoing rejection in the attempt to define novel immunological markers that could predict rejection. Methods We conducted an observational retrospective study on eight consecutive explanted grafts for chronic rejection and on transbronchial cryobiopsies (TCB) obtained from 24 consecutive patients during the first year LuTx follow-up. A broad spectrum of immunohistochemical analysis was carried out (PD1/CD279, PDL1/CD274, CTLA4/CD152, CD4, CD8, hFoxp3, TIGIT, TOX, B-Cell-Specific Activator Protein). Of those TCB-patients we recorded at least 1 year follow up of survival, infections and rejections (acute and chronic) rate. Results Exhausted (PD1+/TOX+) as well as Treg (PD1+/FOXP3+) lymphocytes were significantly reduced in restrictive allograft syndrome (RAS)-compared to bronchiolitis-obliterans-syndrome (BOS)-rejected lungs. PD1-expressing T-lymphocytes in TCBs correlated (sensitivity 0.69; specificity 1) with the presence of AR and were highly suggestive of CLAD development (sensitivity 0.86; specificity 0.82; overall 10 times higher risk of developing CLAD) at one-year follow-up. Conclusion Results herein for the first time show the importance of immunological checkpoints in the setting of LuTx rejection and indicate that the evaluation of the expression of such proteins could offer a distinct prognostic advantage in monitoring the onset of AR in patients who underwent LuTx. Longitudinal analyses in ampler cohorts will be needed to confirm these data.

Purpose We present the results of a clinical trial (NCT02061462) comparing outcomes after lung transplantation (LT) of subjects receiving lungs from donation after brain death (DBD) donors with that of subjects receiving lungs from donation after circulatory death (DCD) donors, procured using our original open lung strategy. Briefly, our protocol consists of a non-rapid normothermic open-lung procurement using recruitment manoeuvres, protective ventilation and CPAP without topical cooling. Methods We evaluated patients undergoing bilateral LT from 11/2014 to 07/2019; exclusion criteria: recipients ≤14 years, re-LT, donors ≥65 years, DCD category I and IV. Variables were prospectively recorded as well as respiratory functional parameters in the first year. Results We performed 143 LT; 22 cases were excluded, 121 were enrolled: 11 recipients received lungs from DCD donors (5 and 6 from DCD category II and III, respectively). The two groups had similar features. Most of the subjects had cystic fibrosis (72,7% and 61,9% of DCD and DBD, respectively). DCD donors’ BMI was significantly higher (p=0.022); 15,5% of DBD grafts underwent machine perfusion. Duration of postoperative mechanical ventilation was higher in the DCD group (DCD vs DBD=2 vs 1 day, p= 0.011). Incidence of grade 3 primary graft dysfunction was 27,3% in the DCD group and 18,2% in the DBD group (p=0.742). Cold ischemia and preservation times were significantly higher in the DCD group (p Conclusion Regardless of the small study population, our results are encouraging. Our data show the feasibility of LT from DCD donors using our original protocol, with adequate grafts function and survival.

Purpose The COVID-19 pandemic has infected millions of people across the world and caused several thousands of deaths. Given advances in extracorporeal life support technology, ECMO for COVID-19 acute respiratory distress syndrome (ARDS) has proven to be successful in sustaining life, however, has left a significant number of patients fully depended on devices and incapable of being weaned. Lung transplantation, as a well-established therapy for end-stage lung disease, has been considered for some patients with COVID-19 ARDS in the absence of lung recovery and the presence of findings suggestive of end-stage lung disease. Methods This is an International collaborative effort to assess the role of lung transplantation in COVID-19 ARDS. There is worldwide representation with centers from US (3), Europe (2) and Asia (1). Patients with COVID-19 ARDS supported on ECMO and/or mechanical ventilation who were deemed unweanable and developed features of end-stage lung disease were evaluated for lung transplantation. We followed ISHLT conventional recipient selection criteria recommendations and a 2 negative COVID-19 PCRs from bronchoalveaolar lavage or viral culture depending on medical urgency. Endpoints We will present demographics, intraoperative challenges, primary graft dysfunction, postoperative complications, survival and functional outcomes of patients with COVID-19 ARDS who underwent lung transplantation. Additionally, referral patterns, reasons for listing denial and waitlist outcomes will be presented. So far, this collaborative group has transplanted 17 patients. There have been no deaths on the waitlist, there was one post-transplant mortality at day 61. Ten patients have been discharged from the hospital and are doing well. Six patients are recovering well however less than 30 days post-transplantation and remain admitted.

Lung resections with bronchoplastic techniques play an important role in the preservation of lung function, in patients with centrally located tumors. Several studies reported oncological outcomes after sleeve resections comparable to pneumonectomy, with lower postoperative mortality and morbidity. Sleeve lobectomy is now considered the procedure of choice for anatomically suitable lesions, regardless of pulmonary function, but is still considered a challenging and technically demanding procedure, especially when carried out by video-assisted thoracic surgery (VATS) approach. The aim of this review article is to describe indications, technical aspects and outcomes of VATS sleeve resections.

Purpose In a previous study on miRNA profiling in bronchoalveolar lavage (BAL) fluid of lung transplanted (LTx) patients we obtained signatures of deregulated miRNAs associated to acute lung allograft dysfunction (ALAD). Now we extended this analysis to chronic dysfunction (CLAD) and to pathways potentially modulated by AR- or CLAD-miRNAs. Methods BALs were obtained from 16 patients who underwent bilateral LTx at our Institution. Mean follow-up time was 21 months (range 17-25). MiRNAs expression in BAL samples collected 7 days (T0), 15 days (T1) and 3 months (T2) after LTx was analyzed using TLDA. The association of miRNAs with pneumonia, acute rejection (AR) or CLAD was examined using ANOVA or Cox regression. The false discovery rate was applied for multiple comparison correction. miRNAs targets were search with miRTarget Link and imported in STRING or WebGestalt databases for functional annotation. Potential targets expression was analyzed by immunohistochemistry (IHC) on transbrochial biopsies. Results We identified one, 9 and 4 BAL-miRNAs whose upregulation is associated with pneumonia, AR or CLAD respectively (Fig. 1A-C). At T1, six BAL-miRNAs predicted CLAD by Cox model. Pathways prediction revealed that AR- or CLAD-miRNAs regulated cell dedifferentiation or WNT signaling, respectively, through the modulation of Sp1 or Bcl2 and cMYC factors (Fig. 1D,E). By IHC, Sp1 was more expressed in biopsies from patients with AR (Fig. 1F) whereas Bcl2 was predominantly detected in lungs from patients with CLAD (Fig. 1G). Conclusion Our results, although preliminary, uncover novel miRNAs-networks involved in AR and CLAD pathogenesis.

Purpose We started our uncontrolled donation after circulatory death (DCD) experience in 2014 with the first successful lung transplantation (LT). After a long period of local logistical reassessment, in 2017 we resumed the process managing both uncontrolled and controlled DCD. This cohort study reviews early outcome of our initial series of LT from DCD donors and matches it with the outcome of patients transplanted with graft from donation after brain death (DBD) donors in the same period. Methods This is a single-institution, retrospective study on data collected prospectively from adult patients who underwent bilateral LT at our Centre between 10/2017 and 07/2019. Our DCD procurement protocol consists of: 1) an in situ graft preservation with open-lung approach (cPAP); 2) non-rapid normothermic lung procurement isolated (only-lung uncontrolled setting) or during abdominal normothermic regional perfusion, namely without pleural topical cooling before the start of PA flushing (multiorgan controlled setting); 3) ex-situ assessment/evaluation with machine perfusion (EVLP or OCS) before LT. Results In the study period 51 subjects respected inclusion criteria (Table). Ten of these were from DCD donors (19.6%; 6 cDCD and 4 uDCD). The flow-chart shows the DCD experience (Image). Conclusion Our DCD program increased the LT number with an adequate early-intermediate outcome, despite extended periods of warm ischemia. Our results suggest that LT from DCD donors is feasible in controlled and uncontrolled setting, in isolated and combined organs procurement.

Purpose Extracorporeal photopheresis has emerged as a promising treatment for chronic rejection. To date, there are no data on extracorporeal photopheresis as induction therapy. We are implementing a single-center, single blind, randomized controlled trial enrolling 24 recipients with cystic fibrosis (CF) who undergo lung transplantation (LTx) randomly allocated in 2 parallel arms: induction with extracorporeal photopheresis plus standard immunosuppressive therapy (ECP) vs. standard immunosuppressive therapy (CTR). We present the interim analysis focused on safety and immunomodulation effectiveness. Methods We recorded every adverse event, including acute rejection (AR), which occurred in the first year after lung transplantation. Immune parameters (activated T cells, Treg, Th17, Th1, NK, PD-1 and PD-L1 expression, IL-10, TNFα, IL-1β, and IFNγ production) were evaluated at different time points in the first year after LTx. Preliminary data on the first ten patients (6 ECP and 4 CTR) are reported. Results No AR episodes were observed and no adverse events due to extracorporeal photopheresis were recorded. In the control arm, one patient died of post-operative infection on 20th postoperative day. In ECP compared to CTR patients: 1) regulatory T cells (Treg) as well as IL10 production by Treg were increased; 2) IL17-secreting Th17 as well as Th1 T cells were reduced; 3) CD107+/CD8+ (perforin-releasing CTL) T lymphocytes were reduced, 4) IL10-producing NK cells were increased; 5) LPS-stimulated IL-10 production was augmented whereas that of TNFα and IL-1β was reduced. Conclusion In the setting of LTx for CF, extracorporeal photopheresis is well tolerated and it results in an overall modulation of immune responses. The positive result of this interim analysis led to the decision of continuing to enroll patients in this randomized trial with the aim of probing the possible positive effect of extracorporeal photopheresis as induction therapy in AR prevention.

Purpose Acute rejection (AR) is common during the first year after lung transplantation (LuTx) and can trigger chronic rejection (CR), the leading cause of late morbidity and mortality of LuTx. Extracorporeal photopheresis (ECP) is a promising treatment for chronic rejection. Few studies focus on ECP as prophylactic therapy of AR and CR. Microvesicles and exosomes (i.e.extracellular vesicles EV) are released into the blood and in bronchoalveolar lavage (BAL) and their role in cell-to-cell communication has been assessed in several studies; EV have been proposed as non-invasive biomarkers to assess lung injury and monitor clinical outcome. Methods We conduct a pilot clinical trial on 24 cystic fibrosis patients undergoing LuTx, randomly allocated in 2 parallel arms: standard immunosuppressive therapy and ECP (ECP) vs standard immunosuppressive therapy alone (CTR). EV concentration was assessed at different time points in blood and BAL in the first year after LuTx (analyzed by nanoparticle tracking analysis Nanosight NS300, Malvern). EV were analyzed for antigen expression with MACSplex bead-based assay. AR episodes and infections were recorded, as far as ECP-related adverse events. Preliminary data on the first 18 patients (9 ECP and 9 CTR) are reported Results ECP was well tollerated and no adverse events or AR occurred in either groups. EV presented highly polydispersed size distributions in a 50-1000 nm range. The expression of EV-associated markers CD63, CD9 and CD81 was detected. Upregulation of platelets (CD62p; p Conclusion The underlying mechanism of ECP remains unresolved. The identification of specific EV antigen signatures may represent a promising approach to better understand the immunomodulatory effects of ECP, both at molecular and cellular level.

The field of video-assisted thoracic surgery (VATS) is still in continuous development. The advent of uniportal technique has added a versatile tool for thoracic surgeons; currently, it is used for minor thoracic procedures including lung wedge resections up to complex thoracic operations (i.e., chest wall resection, pneumonectomy or bronchoplastic resection) demonstrating the versatile nature of this technique (1).