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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.

This study describes the case of an 18-years-old male affected by severe COVID-19, who was receiving bilateral lung transplantation (LT), after 71 days of mechanical ventilation and 55 days of veno-venous extracorporeal membrane oxygenation. From post-operative day 2, early mobilization and physiotherapy treatments were performed. Weaning from mechanical ventilation, the use of non-invasive ventilation and tracheostomy management were included in the treatment. Forty-five days after LT the patient was discharged at home, showing improvements in terms of functional and respiratory parameters, quality of life and mood. While evidences about physiotherapy treatments in lung transplantation post severe COVID-19 remain limited, early approach and a multidisciplinary team may be considered key elements for functional recovery of these subjects.

BackgroundEctopic adrenocorticotropic syndrome (EAS) is a rare cause of endogenous ACTH-dependent Cushing’s syndrome, usually associated with severe hypercortisolism as well as comorbidities. Tumor detection is still a challenge and often requires several imaging procedures. In this report, we describe a case of an ectopic ACTH secretion with a misleading localization of the responsible tumor due to a concomitant rectal carcinoma.Case presentationA 49-year-old man was referred to our Endocrinology Unit due to suspicion of Cushing’s syndrome. His medical history included metastatic rectal adenocarcinoma, diagnosed 5 years ago and treated with adjuvant chemotherapy, radiotherapy and surgical resection. During follow-up, a thoracic computed tomography scan revealed two pulmonary nodules located in the superior and middle lobes of the right lung with a diameter of 5 and 10 mm, respectively. However, these nodules remained radiologically stable thereafter and were not considered relevant. All biochemical tests were suggestive of EAS (basal ACTH levels: 88.2 ng/L, nv 0–46; basal cortisol levels: 44.2 µg/dl, nv 4.8–19.5; negative response to CRH test and high dose dexamethasone suppression test) and radiological localization of the ectopic ACTH-secreting tumor was scheduled. The CT scan revealed a dimensional increase of the right superior lung nodule (from 5 to 12 mm). [68Ga]-DOTA-TOC PET/CT scan was negative, while [18F]-FDG-PET/CT showed a tracer accumulation in the superior nodule. After a multidisciplinary consultation, the patient underwent thoracic surgery that started with two atypical wedge resections of nodules. Frozen section analyses showed a neuroendocrine tumor on the right middle lobe nodule and a metastatic colorectal adenocarcinoma on the superior lesion. Then, a right superior nodulectomy and a right middle lobectomy with mediastinal lymphadenectomy were performed. The final histopathological examination confirmed a typical carcinoid tumor, strongly positive for ACTH. A post-surgical follow-up showed a persistent remission of Cushing’s syndrome.ConclusionsThe present report describes a case of severe hypercortisolism due to EAS not detected by functional imaging methods, in which the localization of ACTH ectopic origin was puzzled by a concomitant metastatic rectal carcinoma. The multidisciplinary approach was crucial for the management of this rare disease.

BackgroundDespite significant improvement in screening programs for cancers of the respiratory district, especially in at-risk subjects, early disease detection is still a major issue. In this scenario, new molecular and non-invasive biomarkers are needed to improve early disease diagnosis.MethodsWe profiled the miRNome in exhaled breath condensate (EBC) and plasma samples from fourteen patients affected by lung AdCa, nine healthy subjects. miRNA signatures were then analyzed in another neoplasia of the respiratory district, i.e. pleural mesothelioma (n = 23) and subjects previously exposed to asbestos were used as controls for this cohort (n = 19). Selected miRNAs were analyzed in purified pulmonary neoplastic or normal epithelial and stromal cell subpopulation from AdCa patients. Finally, the plasmatic miRNA signature was analyzed in a publicly available cohort of NSCLC patients for data validation and in silico analysis was performed with predicted miRNA targets using the multiMiR tool and STRING database.ResultsmiR-597-5p and miR-1260a are significantly over-expressed in EBC from lung AdCa and are associated with AdCa. Similarly, miR-1260a is also up-regulated in the plasma of AdCa patients together with miR-518f-3p and correlates with presence of lung cancer, whereas let-7f-5p is under-expressed. Analysis of these circulating miRNAs in pleural mesothelioma cases confirmed that up-regulation of miR-518f-3p, -597-5p and -1260a, is specific for lung AdCa. Lastly, quantification of the miRNAs in laser-assisted microdissected lung tissues revealed that miR-518f-3p, 597-5p and miR-1260a are predominantly expressed in tumor epithelial cells. Validation analysis confirmed miR-518f-3p as a possible circulating biomarker of NSCLC. In silico analysis of the potentially modulated biological processes by these three miRNAs, shows that tumor bioenergetics are the most affected pathways.ConclusionsOverall, our data suggest a 3-miRNAs signature as a non-invasive and accurate biomarker of lung AdCa. This approach could supplement the current screening approaches for early lung cancer diagnosis.

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.

BACKGROUND: Many studies on fine-needle aspiration biopsy (FNAB) for undetermined pulmonary nodules reported that diagnostic accuracy tended to decline, whereas complication prevalence raised as the size of nodule decreased. Reconsideration on the effectiveness of FNAB would be appropriate considering the dramatic increase in the identification of small nodules with screening programs and new demands of target therapies. The aim of this study was to verify the efficacy of FNAB in pulmonary nodules smaller than 15 mm. METHODS: A retrospective, cohort study was conducted on patients with undetermined solitary pulmonary nodules (SPNs) who underwent computer tomography (CT) guided FNAB at our Institution from January 2012 to December 2014. Patients with SPNs with diameter up to 15 mm were considered; inclusion criteria comprised ASA 3, FEV1

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.

Background Although cardiac autonomic modulation has been studied in several respiratory diseases, the evidence is limited on lung transplantation, particularly on its acute and chronic effects. Thus, we aimed to evaluate cardiac autonomic modulation before and after bilateral lung transplantation (BLT) through a prospective study on patients enrolled while awaiting transplant. Methods Twenty-two patients on the waiting list for lung transplantation (11 women, age 33 [24–51] years) were enrolled in a prospective study at Ospedale Maggiore Policlinico Hospital in Milan, Italy. To evaluate cardiac autonomic modulation, ten minutes ECG and respiration were recorded at different time points before (T0) and 15 days (T1) and 6 months (T2) after bilateral lung transplantation. As to the analysis of cardiac autonomic modulation, heart rate variability (HRV) was assessed using spectral and symbolic analysis. Entropy-derived measures were used to evaluate complexity of cardiac autonomic modulation. Comparisons of autonomic indices at different time points were performed. Results BLT reduced HRV total power, HRV complexity and vagal modulation, while it increased sympathetic modulation in the acute phase (T1) compared to baseline (T0). The HRV alterations remained stable after 6 months (T2). Conclusion BLT reduced global variability and complexity of cardiac autonomic modulation in acute phases, and these alterations remain stable after 6 months from surgery. After BLT, a sympathetic predominance and a vagal withdrawal could be a characteristic autonomic pattern in this population.

Pulmonary oligo-metastases and oligo-recurrences are terms used to define a set of clinical conditions consisting of limited metastatic malignant disease characterized by an intermediate aggressive behavior compared to diffuse metastatic conditions. If the primary tumor has been controlled and extra-thoracic lesions are excluded, there is a suggestion in the medical literature that removal of such lesions could potentially prolong survival. The lungs are a common metastatic spreading site, especially from epithelial malignancies and sarcomas; pulmonary surgical or interventional metastasectomy have been proposed with curative intent in case of limited tumor load (usually less than 5 lesions). There are many series reporting data about colorectal, renal or breast lung metastasectomy, but the absence of multi centric prospective trials determines a lack of definitive evidence, especially for less common tumors such as metastatic germ cell and prostate cancer. They rarely present in the oligo-metastatic form and their management is often based on personal experience. The aim of our article is to review the latest evidence in the treatment of pulmonary metastatic germ cell and prostate tumors. We cover the full range of treatments: from surgery to ablative radiotherapy and combination of local and systemic therapy. Despite the absence of evidence based guidelines, it emerges that pulmonary metastasectomy should always be considered when general criteria for resection have been met. In germ cell tumors surgery should be mainly reserved for residual disease after chemotherapy, whereas in prostate cancer, pulmonary metastasectomy should be preferred to avoid or delay hormonal deprivation therapy and its side effects.

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

In lung cancer accurate assessment of the mediastinal lymph node status is of paramount importance for the stage assignment as well as crucial for the therapeutic plan. TAC and positron emission tomography (PET) are valuable tools to achieve a preliminary picture of the mediastinal staging but Endobronchial ultrasound-transbronchial needle aspiration (EBUS-TBNA) is considered the first choice for investigating mediastinal lymph nodes as recommended by updated guide-lines. Despite the EBUS-TBNA sensitivity is satisfactory, it is not high enough to exclude mediastinal lymph node metastases; therefore devices and technologies were implemented to increase its sensitivity. The purpose of this narrative review is to describe the tools aimed at correctly interpreting sonographic patterns during EBUS and maximizing the diagnostic accuracy of TBNA. The bibliographic research identified 354 articles potentially related to the purpose of the current review and after accurate reading we selected 21 articles. Eight articles focused on the sonographic features of lymph nodes found during EBUS, 2 papers considered the Doppler patterns and, finally, 18 studies analyzed the advantages of ultrasound elastography. Sonographic features, vascular patterns and ultrasound elastography have proved to be helpful in directing the operator to biopsy the most suspect lymph node, especially in patients with CT-negative and/or PET-negative mediastinum.

We herein characterize the immunopathological features of two Italian COVID-19 patients who underwent bilateral lung transplantation (bLTx). Removed lungs underwent histopathological evaluation. Gene expression profiling (GEP) for immune-related signatures was performed on lung specimens and SARS-CoV-2-stimulated peripheral blood mononuclear cells (PBMCs). Cytokine levels were measured on lungs, bronchoalveolar lavage fluids and in culture supernatants. Pathological assessment showed extensive lung damage with the pattern of proliferative to fibrotic phases, with diffuse alveolar damage mimicking usual interstitial pneumonia (UIP). Lungs’ GEP revealed overexpression of pathogen recognition receptors, effector cytokines and chemokines, immune activation receptors and of the inflammasome components. Multiplex cytokine analysis confirmed a proinflammatory state, with high levels of monocyte/macrophage chemotactic and activating factors and of IL-6 and TNF-α. A similar profile was observed in SARS-CoV-2-stimulated PBMCs collected 7 days after transplant. The pattern of tissue damage observed in the lungs suggests that this may represent the output of protracted disease, resembling a diffuse UIP-like picture. The molecular immune profiling supports the paradigm of a persistent proinflammatory state and sustained humoral immunity, conditions that are maintained despite the iatrogenic immunosuppression.

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.

Despite the promising results achieved so far in long-term survival after lung transplantation (LuTx), airway complications (ACs) still arise in the post-operative period. Early diagnosis and prompt treatment of ACs play a critical role in preventing their onset. Specifically, large bronchi ischemia has been recognized as a triggering factor for ACs. Autofluorescence bronchoscopy, which was first introduced for early cancer diagnosis, displays ischemic mucosae as red spots, while normal vascularized mucosae appear in green. The aim of this study is to investigate whether a significant correlation exists between ACs and the red/green (RG) ratio detected on scheduled autofluorescence bronchoscopy up to 1 year after LuTx. This prospective, observational, single-center cohort study initially considered patients who underwent LuTx between July 2014 and February 2016. All patients underwent concomitant white-light and autofluorescence bronchoscopy at baseline (immediately after LuTx), on POD7, POD14, POD21, POD28, POD45, 3 months, 6 months, and 1 year after LuTx. An autofluorescence image of the first bronchial carina distal to the anastomosis was captured and analyzed using histograms for red and green pixels; the R/G ratio was then recorded. Potential ACs were classified according according to the presence of a white-light following the MDS (macroscopic aspect, diameter and suture) criteria. The authors assessed the association between the R/G ratio and the ACs occurrence using a generalized estimating equations model. Thirty-one patients met the inclusion criteria and were therefore selected. Out of a total of 53 bronchial anastomoses, 8 developed complications (late bronchial stenosis), with an average onset time of 201 days after LuTx. ACs showed a similar baseline covariate value when compared to anastomoses that involved no complication. Generalized estimating equations regression indicated a clear association over time between the R/G ratio and the rise of complications (p = 0.023). The authors observed a significant correlation between post-anastomotic stenosis and the delayed decrease of the R/G ratio. Preliminary outcomes suggest that autofluorescence bronchoscopy may be an effective and manageable diagnostic tool, proving complementary to other instruments for early diagnosis of ACs after LuTx. Further research is needed to confirm and detail preliminary findings.

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.

Limited data are currently available regarding the course of COVID-19 in lung and solid organ transplant recipients. We hereby present four cases of SARS-CoV-2 pneumonia in lung transplant recipients from our center, set in Milan, Italy. We reduced immunosuppressive regimen in all these patients, typically holding the antiproliferative agent and augmenting steroids; everybody received hydroxychloroquine, initial empiric antibiotic treatment with piperacillin/tazobactam, and high-dose low molecular weight heparin. Clinical course seemed favorable in three of our patients, but one of them deteriorated after 10 days of hospitalization, probably due to an acute form of graft dysfunction triggered both by COVID-19 and a nosocomial bacterial infection, and eventually died. Although short-term prognosis could be considered benign in the majority of our patients, we should carefully monitor these individuals in order to detect early sign of clinical deterioration and graft dysfunction in the next few months.

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

Background Chest drainage systems are affected by intra and inter-observer variability and poor sensibility in detecting minimal or apparent air leaks. Objectives Overcome intra and inter-observer variability in detecting air leaks. Methods After surgery, a single apical chest tube was connected to the Drentech™ PalmEVO device and air leaks were checked twice a day by observation of both bubbles-in-the-chamber and digital data. Results On a total of 624 observations, disagreement between digital and traditional systems was recorded in 60(9.6%) cases. In 25(21.4%) patients, a disagreement was recorded. Overall, the digital evaluation influenced clinical management in 13(52%). In 10(40%) patients with temporary discordant features, the presence of high pleural fluid output led to a progressive final concordance. Conclusions Disagreement between traditional and digital systems in checking air leaks is not negligible. Digital systems could give advantages in making an objective assessment of air leaks, standardizing the timing of chest tube removal.

Although the literature demonstrates that cardiac autonomic control (CAC) might be impaired in patients with chronic pulmonary diseases, the interplay between CAC and disease severity in end-stage lung disease has not been studied yet. We investigated the effects of end-stage lung disease on CAC through the analysis of heart rate variability (HRV) among patients awaiting lung transplantation. Forty-nine patients on the waiting list for lung transplantation (LTx, 19 men, age 38 &plusmn, 15 years) and 49 healthy non-smoking controls (HC, 22 men, age 40 &plusmn, 16 years) were enrolled in a case&ndash, control study at Policlinico Hospital in Milan, Italy. LTx patients were divided into two groups, according to disease severity evaluated by the Lung Allocation Score (LAS). To assess CAC, electrocardiogram (ECG) and respiration were recorded at rest for 10 min in supine position and for 10 min during active standing. Spectral analysis identified low and high frequencies (LF, sympathetic, and HF, vagal). Symbolic analysis identified three patterns, i.e., 0V% (sympathetic) and 2UV% and 2LV% (vagal). Compared to HCs, LTx patients showed higher markers of sympathetic modulation and lower markers of vagal modulation. However, more severely affected LTx patients, compared to less severely affected ones, showed an autonomic profile characterized by loss of sympathetic modulation and predominant vagal modulation. This pattern can be due to a loss of sympathetic rhythmic oscillation and a subsequent prevalent respiratory modulation of heart rate in severely affected patients.

Primary spontaneous pneumothorax (PSP) is a commonly known condition due to the accumulation of air in the pleural space in otherwise healthy people, without apparent underlying lung disease. To date, the exact pathogenesis of PSP is unclear, but it still represents a public health issue. We performed a review of the literature concerning the epidemiology of PSP, examining age of onset and presentation symptoms, in order to assess the possible correlation between these characteristics and its occurrence. Data concerning age, signs, and symptoms were collected. For description purposes, information regarding aetiological and anthropomorphic data was also gathered. In total, 265 papers were evaluated. Regarding age of onset, PSP is a disease that can occur in a broad age group with a double cluster (15-30 and 40-45 yr). Regarding symptoms, pain and dyspnoea (in its various forms) are the most described in PSP. Pain was recorded in 69.25% (range, 9-100%) of the population studied, whereas dyspnoea was present in an average of 54.55% (range, 27-77.1%). Tobacco exposure seems to play an important role in the early onset of PSP. Concerning age at presentation, this review highlights that PSP can occur over a broad age range. The literature appears to be consistent in reporting PSP occurrence mostly below 45 years of age. Asymptomatic PSP is an almost unseen entity. Finally, of pollutants, cigarette smoking should be considered as the most significant exogenous risk factor in the development of PSP.

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.

IntroductionAnesthetic care in patients undergoing thoracic surgery presents specific challenges that require a multidisciplinary approach to management. There remains a need for standardized, evidence-based, continuously updated guidelines for perioperative care in these patients.MethodsA multidisciplinary expert group, the Perioperative Anesthesia in Thoracic Surgery (PACTS) group, was established to develop recommendations for anesthesia practice in patients undergoing elective lung resection for lung cancer. The project addressed three key areas: preoperative patient assessment and preparation, intraoperative management (surgical and anesthesiologic care), and postoperative care and discharge. A series of clinical questions was developed, and literature searches were performed to inform discussions around these areas, leading to the development of 69 recommendations. The quality of evidence and strength of recommendations were graded using the United States Preventive Services Task Force criteria.ResultsRecommendations for intraoperative care focus on airway management, and monitoring of vital signs, hemodynamics, blood gases, neuromuscular blockade, and depth of anesthesia. Recommendations for postoperative care focus on the provision of multimodal analgesia, intensive care unit (ICU) care, and specific measures such as chest drainage, mobilization, noninvasive ventilation, and atrial fibrillation prophylaxis.ConclusionsThese recommendations should help clinicians to improve intraoperative and postoperative management, and thereby achieve better postoperative outcomes in thoracic surgery patients. Further refinement of the recommendations can be anticipated as the literature continues to evolve.

Background: Second cancer is the leading cause of death in lymphoma survivors, with lung cancer representing the most common solid tumor. Limited information exists about the treatment and prognosis of second lung cancer following lymphoma. Herein, we evaluated the outcome and prognostic factors of Lung Cancer in Lymphoma Survivors (the LuCiLyS study) to improve the patient selection for lung cancer treatment. Methods: This is a retrospective multicentre study including consecutive patients treated for lymphoma disease that subsequently developed non-small cell lung cancer (NSCLC). Data regarding lymphoma including age, symptoms, histology, disease stage, treatment received and lymphoma status at the time of lung cancer diagnosis, and data on lung carcinoma as age, smoking history, latency from lymphoma, symptoms, histology, disease stage, treatment received, and survival were evaluated to identify the significant prognostic factors for overall survival. Results: Our study population included 164 patients, 145 of which underwent lung cancer resection. The median overall survival was 63 (range, 58-85) months, and the 5-year survival rate 54%. At univariable analysis no-active lymphoma (HR: 2.19; P=0.0152); early lymphoma stage (HR: 1.95; P=0.01); adenocarcinoma histology (HR: 0.59; P=0.0421); early lung cancer stage (HR: 3.18; P

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.

Background: Despite advances in perioperative care and surgical techniques, patients undergoing pulmonary lobectomy are still at high risk for postoperative complications. Among interventions expected to reduce complications, continuous positive airway pressure (CPAP) is a discussed option. This trial aims to test the hypothesis whether prophylactic application of CPAP following pulmonary lobectomy can reduce postoperative complications. Methods: The study was designed as a prospective, randomized, controlled trial. Patients with clinical stage I non-small cell lung cancer scheduled for pulmonary lobectomy were eligible and were trained for the use of CPAP interface. The control group received standard postoperative pain management and physiotherapy; in addition, the study group received CPAP (PEEP 8–12 cmH 2 O, 2 hours thrice daily for three days). Results: After the appropriate selection, 163 patients were considered for the analysis: 82 patients constituted the control group, 81 the study group. The two groups were substantially comparable for preoperative parameters. The rate of postoperative complications was lower in the study group (24.7% vs . 43.9%; P=0.015) as well as the hospital stay (6 vs . 7 days; P=0.031). The stepwise logistic regression model identified: CPAP [odd ratio (OR): 0.3026, CI: 0.1389–0.6591], smoke habits [OR: 2.5835, confidence interval (CI): 1.0331–6.4610] and length of surgery in minutes (OR: 1.0102, CI: 1.0042–1.0163) as regressors on postoperative complications. Conclusions: The present trial demonstrated that prophylactic application of CPAP during the postoperative period after pulmonary lobectomy for stage I non-small cell lung cancer was effective in prevent postoperative complications.

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.

Multi-institutional studies of endobronchial-ultrasound transbronchial needle aspiration (EBUS-TBNA) for mediastinal staging in lung cancer are scarce. It is unclear if the high diagnostic performance of EBUS-TBNA reported by experts' guidelines can be generally achieved.This is a retrospective study performed in five tertiary referral centers of thoracic surgery in Italy, to assess the EBUS-TBNA diagnostic performance in patients with non-small cell lung cancer (NSCLC). Patient inclusion criteria were: both genders;18 years old; with suspect/confirmed NSCLC; undergoing EBUS-TBNA for mediastinal node enlargement at computed tomography (size1 cm, ≤3 cm) and/or pathological uptake at positron emission tomography. Altogether we included 485 patients [male, 366; female, 119; median age, 68 years (IQR, 61-74 years)] undergoing mediastinal staging between January 2011 and July 2016. All EBUS-TBNAs were performed by experienced bronchoscopists, without pre-defined quality standards. Depending on usual practice in each center, EBUS-TBNA was done under conscious sedation, with 21- or 22-Gauge (G) needle, and specimen preparation was cell-block, or cytology slides, or core-tissue. Sampling was classified inadequate in absence of lymphocytes, or when sample was insufficient. We analyzed the EBUS-TBNA procedural steps likely to influence the rate of adequate samplings (diagnostic yield).EBUS-TBNA sensitivity, negative predictive value (NPV) and accuracy respectively were 90%, 78% and 93% in the whole cohort. At multivariate analysis, use of 21-G needle was associated with better diagnostic yield (P0.001). Center and specimen processing technique were not independent factors affecting EBUS-TBNA diagnostic yield.In this multicentric study, EBUS-TBNA was a highly sensitive and accurate method for NSCLC mediastinal node staging. Results indicate better performance of EBUS-TBNA with 21-G needle, and suggest that specimen processing technique could be chosen according to the local practice preference.

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.

A plethora of physiological and biochemical changes occur during normal pregnancy. The changes in the respiratory system have not been as well elucidated, in part because radioimaging is usually avoided during pregnancy. We aimed to use several noninvasive methods to characterize the adaptation of the respiratory system during the full course of pregnancy in preparation for childbirth. Eighteen otherwise healthy women (32.3 ± 2.8 yr) were recruited during early pregnancy. Spirometry, optoelectronic plethysmography, and ultrasonography were used to study changes in chest wall geometry, breathing pattern, lung and thoraco-abdominal volume variations, and diaphragmatic thickness in the first, second, and third trimesters. A group of nonpregnant women were used as control subjects. During the course of pregnancy, we observed a reorganization of rib cage geometry, in shape but not in volume. Despite the growing uterus, there was no lung restriction (forced vital capacity: 101 ± 15% predicted), but we did observe reduced rib cage expansion. Breathing frequency and diaphragmatic contribution to tidal volume and inspiratory capacity increased. Diaphragm thickness was maintained (1st trimester: 2.7 ± 0.8 mm, 3rd trimester: 2.5 ± 0.9 mm; P = 0.187), possibly indicating a conditioning effect to compensate for the effects of the growing uterus. We conclude that pregnancy preserved lung volumes, abdominal muscles, and the diaphragm at the expense of rib cage muscles.NEW & NOTEWORTHY Noninvasive analysis of the kinematics of the chest wall and the diaphragm during resting conditions in pregnant women revealed significant changes in the pattern of thoracoabdominal breathing across the trimesters. That is, concomitant with the progressive changes of chest wall shape, the diaphragm increased its contribution to both spontaneous and maximal breathing, maintaining its thickness despite its lengthening due to the growing uterus. These results suggest that during pregnancy the diaphragm is conditioned to optimize its active role provided during parturition.

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.