Extracorporeal membrane oxygenation for grade 3 primary graft dysfunction after lung transplantation: Long-term outcomes.

INTRODUCTION: Extracorporeal membrane oxygenation (ECMO) is an efficient and innovative therapeutic tool for primary graft dysfunction (PGD). However, its effect on survival and long-term lung function is not well known. This study evaluated those parameters in patients with PGD requiring ECMO. METHOD: This single-center, retrospective study included patients who underwent LTx at our institute between January 2007 and December 2013. Patients and disease characteristics, survival, and pulmonary function tests were recorded. RESULTS: A total of 309 patients underwent LTx during the study period and 211 were included. The patients were predominantly male (53.5%), the median age was 39 years, and the primary pathology was suppurative disease (53.1%). ECMO for PGD was mandatory in 24 (11.7%) cases. Mortality at 3 months in the ECMO group was 50% (N = 12). However, long-term survival after PGD did not correlate with ECMO. Forced expiratory volume and vital capacity were significantly reduced in patients with PGD requiring ECMO, especially those with idiopathic pulmonary fibrosis. CONCLUSION: Veno-arterial ECMO appears to be suitable for management of PGD after LTx. Patients with PGD requiring ECMO show increased initial mortality; however, long-term survival was comparable with that of other patients in the study. Lung function does not appear to be related to PGD requiring ECMO.

Successful pulmonary arterial embolization followed by curative surgery for a lepidic predominant lung adenocarcinoma with severe hypoxemia.

BACKGROUND: Lepidic predominant adenocarcinoma is characterized by frequent refractory hypoxemia due to intrapulmonary shunting. Severe hypoxemia can induce perioperative complications in case of thoracic surgery. CASE PRESENTATION: We report a case of a 67 year-old woman with localized lepidic adenocarcinoma in the right lower lobe with severe hypoxemia. A selective arterial lung embolization allowed an instantaneous correction of the hypoxemia, and a curative lobectomy was safely performed 1 week after without any complication. The staging was pT3N0M0, and the patient received adjuvant chemotherapy. CONCLUSIONS: This is the first case-report of successful endovascular embolization before curative surgery for a lepidic predominant lung adenocarcinoma.

High Emergency Lung Transplantation: dramatic decrease of waiting list death rate without relevant higher post-transplant mortality.

Many candidates for lung transplantation (LT) die on the waiting list, raising the question of graft availability and strategy for organ allocation. We report the experience of the new organ allocation program, "High Emergency Lung Transplantation" (HELT), since its implementation in our center in 2007. Retrospective analysis of 201 lung transplant patients, of whom 37 received HELT from 1st July 2007 to 31th May 2012. HELT candidates had a higher impairment grade on respiratory status and higher Lung Allocation Score (LAS). HELT patients had increased incidence of perioperative complications (e.g., perioperative bleeding) and extracorporeal circulatory assistance (75% vs. 36.6%, P = 0.0005). No significant difference was observed between HELT and non-HELT patients in mechanical ventilation duration (15.5 days vs. 11 days, P = 0.27), intensive care unit length of stay (15 days vs. 10 days, P = 0.22) or survival rate at 12 (81% vs. 80%), and 24 months post-LT (72.9% vs. 75.0%). Lastly, mortality on the waiting list was spectacularly reduced from 19% to 2% when compared to the non-HELT 2004-2007 group. Despite a more severe clinical status of patients on the waiting list, HELT provided similar results to conventional LT. These results were associated with a dramatic reduction in the mortality rate of patients on the waiting list.

Severe, chronic cough caused by pulmonary arteriovenous malformations in a patient with hereditary haemorrhagic telangiectasia: case report.

BACKGROUND: Patients with pulmonary arteriovenous malformations usually complain of dyspnoea upon exertion, fatigue or migraine, or may be asymptomatic. We describe a patient with an unreported manifestation of a pulmonary arteriovenous malformation: a severe chronic cough. CASE PRESENTATION: A 51-year old Caucasian non-smoking female police officer presented with a chronic cough. She had been diagnosed with hereditary haemorrhagic telangiectasia in 1992. She complained of a severe, dry cough at the time of the diagnosis and a pulmonary arteriovenous malformation in the upper left lobe as demonstrated by CT of the chest. The fistula was occluded and the cough disappeared rapidly but resumed in 1994. Recanalisation of the fistula led to a new embolisation procedure, and the cough disappeared. Similar episodes occurred in 1998 and 2004, leading to embolisation of a fistula in the right lower lobe and reperfused fistula in the upper left lobe, respectively. The patient was referred to our research team in 2010 because of reappearance of her dry cough that was more pronounced during exercise and exposure to volatile irritants, and absent during the night. Despite extensive investigations, no cause was found other than reperfusion of the fistula in the left upper lobe. The malformation was not accessible to embolisation, leading us to recommend surgical excision of the malformation. A surgeon undertook atypical resection of the left upper lobe in 2012. The cough disappeared immediately after surgery and has not recurred. CONCLUSION: Physicians caring for patients with pulmonary arteriovenous malformations should know that a severe, chronic cough can be caused by the malformation. A cough associated with a pulmonary arteriovenous malformation can be treated effectively by embolisation but may resume in cases of reperfusion of the malformation. In our case, the severity of the cough led to surgical excision because embolisation was not possible. The mechanism of action of this cough remains to be determined.

Anoctamin 1 dysregulation alters bronchial epithelial repair in cystic fibrosis.

Cystic fibrosis (CF) airway epithelium is constantly subjected to injury events due to chronic infection and inflammation. Moreover, abnormalities in CF airway epithelium repair have been described and contribute to the lung function decline seen in CF patients. In the last past years, it has been proposed that anoctamin 1 (ANO1), a Ca(2+)-activated Cl(-) channel, might offset the CFTR deficiency but this protein has not been characterized in CF airways. Interestingly, recent evidence indicates a role for ANO1 in cell proliferation and tumor growth. Our aims were to study non-CF and CF bronchial epithelial repair and to determine whether ANO1 is involved in airway epithelial repair. Here, we showed, with human bronchial epithelial cell lines and primary cells, that both cell proliferation and migration during epithelial repair are delayed in CF compared to non-CF cells. We then demonstrated that ANO1 Cl(-) channel activity was significantly decreased in CF versus non-CF cells. To explain this decreased Cl(-) channel activity in CF context, we compared ANO1 expression in non-CF vs. CF bronchial epithelial cell lines and primary cells, in lung explants from wild-type vs. F508del mice and non-CF vs. CF patients. In all these models, ANO1 expression was markedly lower in CF compared to non-CF. Finally, we established that ANO1 inhibition or overexpression was associated respectively with decreases and increases in cell proliferation and migration. In summary, our study demonstrates involvement of ANO1 decreased activity and expression in abnormal CF airway epithelial repair and suggests that ANO1 correction may improve this process.

The role of three-dimensional reconstructions in understanding the intersegmental plane: an anatomical study of segment 6.

OBJECTIVES: The identification of the intersegmental plane during lung segmentectomies remains a practical difficulty, notably with minimally invasive approaches. The intraoperative techniques are based on demarcating either the bronchial or the vascular territories. The goal of this study was to evaluate the use of 3-dimensional reconstructions in understanding the intersegmental plane of segment 6. METHODS: Between March and September 2018, Synapse 3-dimensional programme was used to carry out bilateral venous, arterial and bronchial segmentations of segment 6. All computed tomography (CT) scans were contrast-enhanced and of a high resolution (0.6 mm slices). The patients had normal results on respiratory function tests. The volumes obtained from each of the 3 modalities were then compared. The results are presented as mean and standard deviation and as median and interquartile ranges for lung volume measurements. RESULTS: During the aforementioned period, 15 high-resolution chest CT scans were selected (8 men and 7 women). The median age was 70 years. In all of the studied segments (N = 30, 15 right S6 and 15 left S6), the segmental volume of the vein was greater than the segmental volumes of the bronchus and the artery. A significant difference was found between the segmental volumes obtained from the 3 modalities (P = 0.001). The segmental volume of the vein was significantly higher than the segmental volume of the bronchus (P < 0.001) and the segmental volume of the artery (P < 0.001). On the other hand, the segmental volume of the artery was significantly higher than the segmental volume of the bronchus (P = 0.01). CONCLUSIONS: Within the limits of this study, the segmental venous volume of S6 was greater than the volumes of the segmental bronchial and arterial volumes. Thus, depending solely on bronchial techniques might lead to leaving a border zone in venous congestion.

Assessment of lung edema during ex-vivo lung perfusion by single transpulmonary thermodilution: A preliminary study in humans.

BACKGROUND: Single transpulmonary thermodilution (SD) with extravascular lung water index (EVLWI) could become a new tool to better assess lung graft edema during ex-vivo lung perfusion (EVLP). In this study we compare EVLWI with conventional methods to better select lungs during EVLP and to predict post-transplant primary graft dysfunction (PGD). METHODS: We measured EVLWI, arterial oxygen/fraction of inspired oxygen (P/F) ratio, and static lung compliance (SLC) during EVLP in an observational study. At the end of EVLP, grafts were accepted or rejected according to a standardized protocol blinded to EVLWI results. We compared the respective ability of EVLWI, P/F, and SLC to predict PGD. Mann-Whitney U-test, Fisher's exact test, and receiver-operating characteristic (ROC) curve data were used for analysis. p < 0.05 was considered statistically significant. RESULTS: Thirty-five lungs were evaluated by SD during EVLP. Three lungs were rejected for pulmonary edema. Thirty-two patients were transplanted, 8 patients developed Grade 2 or 3 PGD, and 24 patients developed Grade 0 or 1 PGD. In contrast to P/F ratio, SLC, and pulmonary artery pressure, EVLWI differed between these 2 populations (p < 0.001). The area under the ROC for EVLWI assessing Grade 2 or 3 PGD at the end of EVLP was 0.93. Donor lungs with EVLWI >7.5 ml/kg were more likely associated with a higher incidence of Grade 2 or 3 PGD at Day 3. CONCLUSIONS: Increased EVLWI during EVLP was associated with PGD in recipients.

Real-Time Computed Tomography Highlights Pulmonary Parenchymal Evolution During Ex Vivo Lung Reconditioning.

Ex vivo lung perfusion (EVLP) has been developed as a method to reassess and recondition marginal lungs. However, evaluation during procedures is limited to a combination of physiologic variables such as gas exchange, pulmonary mechanics, and pulmonary vascular resistance. The aim of this study was to analyze the feasibility of real-time computed tomographic (CT) imaging to improve the evaluation of the lung during EVLP procedures.

Lung cancer in renal transplant recipients: A case-control study.

INTRODUCTION: Solid organ transplant patients are at heightened risk of several cancers compared to the general population. Secondary to a higher number of procedures and better survival after transplantation, cancer is a rising health concern in this situation. Limited data exist for lung cancer (LC) after renal transplantation. We report here the most important series of renal transplant recipients with lung cancer. METHODS: Retrospective study of all cases of LC diagnosed in three French Renal Transplant Units from 2003 to 2012. A control group consisted of non-transplant patients with LC matched with the cases for age (<30; 30-50; 50-65; >65 years), gender and diagnosis date. We recruited two controls for each case. RESULTS: Thirty patients (median age 60 years; range 29-85; male/female ratio 80/20%) with LC were analysed. LC incidence was 1.89/1000 person-years over the period 2008-2012. All patients were former or active smokers (median 30 pack-years). Transplanted patients had significantly more comorbidities, mainly cardiovascular disease. The median interval of time from kidney transplantation (KT) to diagnosis of LC was 7 years (range 0.5-47 years). LC was incidentally diagnosed in 40%. Most patients (70%) had advanced LC (stage III or IV) disease. Stage of LC at diagnosis was similar in cases and controls. Surgery and chemotherapy were proposed to the same proportion of patients. In cases, mortality was cancer related in 87% and median survival time after diagnosis was 24 months. Survival was not significantly different between the 2 groups. CONCLUSION: Despite frequent medical and radiological examinations, diagnosis of LC is usually made at an advanced stage and the overall prognosis remains poor.

Logistic ex Vivo Lung Perfusion for Hyperimmunized Patients.

Hyperimmunized patients have restricted access to lung transplantation because of the low rate of donor lung availability. Sensitization to human leukocyte antigen is associated with acute rejection, allograft dysfunction, and decreased survival. Prospective crossmatching could allow matching a lung graft with the recipient; however, such a strategy would increase graft ischemia, with a worse impact on the long-term results of lung transplantation. We used logistic ex vivo lung perfusion for 3 patients at the Foch Hospital while waiting for a negative result of the prospective crossmatching and then moved forward to lung transplantation. All patients are alive 3 years after bilateral lung transplantation.

Feasibility and results of a fast-track protocol in thoracic surgery.

BACKGROUND: A rehabilitation program, a multimodal strategy favoring rapid postoperative return to autonomy, has rarely been undertaken after thoracic surgery compared to colectomy. The primary outcome of this fast-track program was the length of postoperative stay. Secondary outcomes concerned the feasibility of this strategy, the incidence of postoperative complications and 3-month postoperative mortality. METHODS: Patients were included in this prospective single-center observational study if they were scheduled for lung resection (lobectomy or wedge resection) performed by posterolateral thoracotomy. The rehabilitation program, coordinated by a referent nurse, included a list of actions to be done, especially early feeding and ambulation, multimodal analgesia including epidural analgesia, early removal of chest tube. RESULTS: One hundred and two patients were included in total with two exclusions (failure of epidural analgesia). The postoperative hospital stay was 8 (7-10) days (median [25-75th percentiles]); this duration was similar to that of the historical cohort which was 9 [7-13] days (P=0.06). Most actions were conducted with a high level of acceptance except for the insertion of a single chest tube (19%) and its removal later than expected in the program. Only 50% of patients left hospital shortly after exit criteria were met suggesting failure in the organization. Patients' satisfaction rate reached 77% and no postoperative death was reported during the follow-up period. CONCLUSION: A program for early rehabilitation is feasible after thoracotomy. Chest drainage and organization to optimize the length of stay are crucial points.

Techniques and results of lobar lung transplantations.

OBJECTIVES: We report our experience of lobar lung transplantations (LLTs) in patients with small thoracic volume. METHODS: Since 1988, 50 LLTs were done for cystic fibrosis (n=35), fibrosis (n=7), bronchiectasis (n=3), emphysema (n=3) and lymphangiomyomatosis (n=2). There were 44 females and 6 males (mean age 31±13 years, mean size 155±5.5 cm and mean predicted total lung capacity (TLC) 4463±598 ml). Mean ratio between donor and recipient-predicted TLC was 1.65±0.26. Six patients were listed in high emergency, 2 of them on ECMO as a bridge to transplantation. Forty middle/lower right lobe with left lower LLT, four bilateral lower LLT and six split left lung LLT were performed through a clamshell incision (n=12) or a bilateral antero-lateral thoracotomy (n=38), with epidural analgesia in 17 cases. Thirty-two patients were transplanted under circulatory support (CPB n=16, veno-arterial ECMO n=16). In 11 cases, the right venous anastomosis was enlarged by a pericardial cuff. Ischaemic time was 4.4±1.2 h for the first lobe and 6.1±1.3 h for the second. RESULTS: Median mechanical ventilation weaning time was 10.5 (1-136) days. Four patients were extubated in the operating room. Ten patients needed ECMO for primary graft dysfunction. In-hospital mortality was 28% related to sepsis (n=6), PGD (n=3), haemorrhage (n=2), broncho-vascular fistula (n=1), and multiorgan failure (n=2). Eight patients required endoscopic treatments for airway complications. Mean best FEV1 was 72±16% of the theoretical value. The actuarial 3-year and 5-year survival rates were 60 and 46%, respectively. CONCLUSIONS: LLTs are a reliable solution and can be performed with satisfactory functional results and survival rates.

Lung transplantation from initially rejected donors after ex vivo lung reconditioning: the French experience.

OBJECTIVES: Only 15% of brain death donors are considered suitable for lung transplantation (LTx). The normothermic ex vivo lung perfusion technique is used to potentially increase the availability of high-risk lung donors. We report our experience of LTx with initially rejected donors after ex vivo lung reconditioning (EVLR). METHODS: From April 2011 to May 2013, we performed EVLR for 32 pairs of donor lungs deemed unsuitable for transplantation and rejected by the 11 French lung transplant teams. After EVLR, lungs with acceptable function were transplanted. During the same period, 81 double-lung transplantations (DLTx) were used as controls. RESULTS: During EVLR, 31 of 32 donor lungs recovered physiological function with a median PO2/FiO2 ratio increasing from 274 (range 162-404) mmHg to 511 (378-668) mmHg at the end of EVLR (P < 0.0001). Thirty-one DLTx were performed. The incidence of primary graft dysfunction 72 h after LTx was 9.5% in the EVLR group and 8.5% in the control group (P = 1). The median time of extubation, intensive care unit and hospital lengths of stay were 1, 9 and 37 days in the EVLR group and 1 (P = 0.17), 6 (P = 0.06) and 28 days (P = 0.09) in the control group, respectively. Thirty-day mortality rates were 3.3% (n = 1) in the EVLR group and 3.7% (n = 3) in the control group (P = 0.69). One-year survival rates were 93% in the EVLR group and 91% in the control group. CONCLUSIONS: EVLR is a reliable and repeatable technique that offers a significant increase of available donors. The results of LTx with EVLR lungs are similar to those obtained with conventional donors.

Intraoperative occurrence of a pneumopericardium during double-lung transplantation.

Pneumopericardium is rare and has been reported secondary to chest trauma. We report a case of tension pneumopericardium occurring during double-lung transplantation, where intraoperative transoesophageal echocardiography first showed a hypokinetic left ventricle and a few minutes later a compression of its anterolateral portion due to pneumopericardium. Although the pericardium was opened, left ventricular function remained depressed, necessitating extracorporeal membrane oxygenation, which was withdrawn after 48 h of assistance when left ventricular function had recovered. The patient was extubated on the seventh postoperative day but died of multiorgan failure on the 64 th postoperative day.

Advances in lung transplantation for cystic fibrosis that may improve outcome.

OBJECTIVE: To study the advances in the management of lung-transplanted patients for cystic fibrosis in our centre and their impact on the outcome. METHODS: A retrospective study has included 100 patients who underwent lung transplantation for cystic fibrosis between 1 January 1990 and 15 January 2007. There were 78 sequential double-lung transplantations and 22 lobar transplantations. This series has been equally divided in two groups according to the date of transplantation: group I, before September 2003 and, group II, after September 2003. RESULTS: Recipient characteristics were similar in both groups. In group II, donors were older (40 vs 33 years, respectively, P=0.013), with lower partial pressure of oxygen in arterial blood (PaO(2))/fractional inspired oxygen (FiO(2)) ratios (372 vs 427 mmHg, P=0.022). In group II, recipients received, more often, thoracic epidural analgesia (n=35 vs n=13, P<0.001), the surgical approach was mostly a sternum-sparing bilateral anterior thoracotomy (n=42 vs n=9, P<0.001), and lobar transplantations were performed more frequently (n=15 vs n=7, P=0.30). Early tracheal extubation was more frequent in group II (P=0.005). The overall median survival time was 52 months. In the first group, 1-, 2- and 3-year survival rates were 75%, 65% and 55%, respectively, whereas in the second group, these survival rates were 88%, 78% and 69%, respectively (P=0.09). CONCLUSIONS: The acceptance of marginal donors and the frequent practice of lobar transplantations allowed an increasing number of lung transplantations for cystic fibrosis over time. Concomitantly, the extensive use of thoracic epidural analgesia has increased the rate of early extubation and contributed to a trend towards a survival improvement.

Asymptomatic spinal canal migration of clavicular K-wire at the cervicothoracic junction.

Unstable clavicular fractures can be treated surgically with pins and wires or with plates. The migration of metallic devices such as Kirschner wires (K-wires) from the shoulder to a variety of anatomical proximal and distal locations is well documented. Spinal migration, however, is rare and is normally associated with severe spinal injury. This article presents the case of a man who presented with cervicothoracic migration of a K-wire after treatment of a clavicular fracture sustained during a sports accident. The distinctive feature in this case, when compared to the existing literature, is its fortuitous detection by imaging studies and its surgical removal without neurological sequelae.