Outcomes of lung transplantation for pleuroparenchymal fibroelastosis: A French multicentric retrospective study.

BACKGROUND: Pleuroparenchymal fibroelastosis (PPFE) has no currently available specific treatment. Benefits of lung transplantation (LT) for PPFE are poorly documented. METHODS: We conducted a nation-wide multicentric retrospective study in patients who underwent lung or heart-lung transplantation for chronic end-stage lung disease secondary to PPFE between 2012 and 2022 in France. RESULTS: Thirty-one patients were included. At transplantation, median age was 48 years [IQR 35-55]. About 64.5% were women. Twenty-one (67.7%) had idiopathic PFFE. Sixteen (52%) had bilateral LT, 10 (32%) had single LT, 4 (13%) had lobar transplantation and one (3%) had heart-lung transplantation. Operative mortality was 3.2%. Early mortality (<90 days or during the first hospitalization) was 32%. Eleven patients (35.5%) underwent reoperation for hemostasis. Eight (30.8%) experienced bronchial complications. Mechanical ventilation time was 10 days [IQR 2-55]. Length of stay in intensive care unit and hospital were 34 [IQR 18-73] and 64 [IQR 36-103] days, respectively. Median survival was 21 months. Post-transplant survival rates after 1, 2, and 5 years were 57.9%, 42.6% and 38.3% respectively. Low albuminemia (p = 0.046), FVC (p = 0.021), FEV1 (p = 0.009) and high emergency lung transplantation (p = 0.04) were associated with increased early mortality. Oversized graft tended to be correlated to a higher mortality (p = 0.07). CONCLUSION: LT for PPFE is associated with high post-operative morbi-mortality rates. Patients requiring high emergency lung transplantation with advanced disease, malnutrition, or critical clinical status experienced worse outcomes. GOV IDENTIFIER: NCT05044390.

Impact of recipient and donor pretransplantation body mass index on early postosperative complications after lung transplantation.

BACKGROUND: Prior studies have assessed the impact of the pretransplantation recipient body mass index (BMI) on patient outcomes after lung transplantation (LT), but they have not specifically addressed early postoperative complications. Moreover, the impact of donor BMI on these complications has not been evaluated. The first aim of this study was to assess complications during hospitalization in the ICU after LT according to donor and recipient pretransplantation BMI. METHODS: All the recipients who underwent LT at Bichat Claude Bernard Hospital, Paris, between January 2016 and August 2022 were included in this observational retrospective monocentric study. Postoperative complications were analyzed according to recipient and donor BMIs. Univariate and multivariate analyses were also performed. The 90-day and one-year survival rates were studied. P < 0.05 was considered to indicate statistical significance. The Paris-North Hospitals Institutional Review Board approved the study. RESULTS: A total of 304 recipients were analyzed. Being underweight was observed in 41 (13%) recipients, a normal weight in 130 (43%) recipients, and being overweight/obese in 133 (44%) recipients. ECMO support during surgery was significantly more common in the overweight/obese group (p = 0.021), as were respiratory complications (primary graft dysfunction (PGD) (p = 0.006), grade 3 PDG (p = 0.018), neuroblocking agent administration (p = 0.008), prone positioning (p = 0.007)), and KDIGO 3 acute kidney injury (p = 0.036). However, pretransplantation overweight/obese status was not an independent risk factor for 90-day mortality. An overweight or obese donor was associated with a decreased PaO2/FiO2 ratio before organ donation (p < 0.001), without affecting morbidity or mortality after LT. CONCLUSION: Pretransplantation overweight/obesity in recipients is strongly associated with respiratory and renal complications during hospitalization in the ICU after LT.

[Infectious pneumonia favored by paraneoplastic Cushing syndrome in a pulmonary carcinoid tumor]. / Pneumopathie infectieuse favorisée par un syndrome de Cushing paranéoplasique d'une tumeur carcinoïde pulmonaire.

INTRODUCTION: Ectopic Cushing's syndrome (CS) is a rare condition nevertheless well-known to endocrinologists. The pneumologist may be called upon to treat CS not only because bronchial carcinoid tumors are the most frequent source of ectopic ACTH secretion, but also due to the fact that the immunosuppression induced by hypercorticism favors lower respiratory tract infections. CASE REPORT: We report the case of a female patient presenting with acute respiratory failure secondary to Enterobacter cloacae pneumonia exacerbated by SC. Further investigations confirmed ectopic ACTH secretion and revealed a right upper lobe pulmonary nodule. After appropriate antibiotic therapy, the patient received preoperative adrenolytic treatment. Management by right upper lobectomy resulted in the extraction of a 12mm tumor. Pathological analysis was consistent with the diagnosis of a typical carcinoid tumor. Immunohistochemistry confirmed ACTH secretion by the tumor. Even though the postoperative course showed CS regression, the patient developed adrenal insufficiency. CONCLUSION: Ectopic CS induces immunosuppression, which aggravates lower respiratory tract infections. Search for a pulmonary neuroendocrine tumor should be systematic. Following control of the secretory syndrome by adrenolytic treatment, and if the diagnosis of carcinoid tumor is confirmed, surgical treatment is the preferred option.

Controlled donation after circulatory death lung transplantation: Results of the French protocol including in situ abdominal normothermic regional perfusion and ex vivo lung perfusion.

BACKGROUND: The French national protocol for controlled donation after circulatory determination of death (cDCD) includes normothermic regional perfusion (NRP) in case of abdominal organ procurement and additional ex-vivo lung perfusion (EVLP) before considering lung transplantation (LT). METHODS: We made a retrospective study of a prospective registry that included all donors considered for cDCD LT from the beginning of the program in May 2016 to November 2021. RESULTS: One hundred grafts from 14 donor hospitals were accepted by 6 LT centers. The median duration of the agonal phase was 20 minutes [2-166]. The median duration from circulatory arrest to pulmonary flush was 62 minutes [20-90]. Ten lung grafts were not retrieved due to prolonged agonal phases (n = 3), failure of NRP insertion (n = 5), or poor in situ evaluation (n = 2). The remaining 90 lung grafts were all evaluated on EVLP, with a conversion rate of 84% and a cDCD transplantation rate of 76%. The median total preservation time was 707 minutes [543-1038]. Seventy-one bilateral LTs and 5 single LTs were performed for chronic obstructive pulmonary disease (n = 29), pulmonary fibrosis (n = 21), cystic fibrosis (n = 15), pulmonary hypertension (n = 8), graft-versus-host disease (n = 2), and adenosquamous carcinoma (n = 1). The rate of PGD3 was 9% (n = 5). The 1-year survival rate was 93.4%. CONCLUSION: After initial acceptance, cDCD lung grafts led to LT in 76% of cases, with outcomes similar to those already reported in the literature. The relative impacts of NRP and EVLP on the outcome following cDCD LT should be assessed prospectively in the context of comparative studies.

[Adipocytes, adipokines and metabolic alterations in pulmonary fibrosis]. / Adipocytes, adipokines et altérations métaboliques dans la fibrose pulmonaire.

Idiopathic pulmonary fibrosis (IPF) is a fatal respiratory disease characterized by severe remodeling of the lung parenchyma, with an accumulation of activated myofibroblasts and extracellular matrix, along with aberrant cellular differentiation. Within the subpleural fibrous zones, ectopic adipocyte deposits often appear. In addition, alterations in lipid homeostasis have been associated with IPF pathophysiology. In this mini-review, we will discuss the potential involvement of the adipocyte secretome and its paracrine or endocrine-based contribution to the pathophysiology of IPF, via protein or lipid mediators in particular.

[Updated indications and contraindications in 2022 for lung transplantation in France]. / Transplantation pulmonaire en France : actualisation des indications et contre-indications en 2022.

Lung transplantation (LTx) is the last-resort treatment for end-stage respiratory insufficiency, whatever its origin, and represents a steadily expanding field of endeavor. Major developments have been impelled over the years by painstaking efforts at LTx centers to improve donor and recipient selection, and multifaceted attempts have been made to meet the challenges raised by surgical management, perioperative care, and long-term medical complications. The number of procedures has increased, leading to improved post-LTx prognosis. One consequence of these multiple developments has been a pruning away of contraindications over time, which has, in some ways, complicated the patient selection process. With these considerations in mind, the Francophone Pulmonology Society (Société de Pneumology de Langue Française [SPLF]) has set up a task force to produce up-to-date working guidelines designed to assist pulmonologists in managing end-stage respiratory insufficiency, determining which patients may be eligible for LTx, and appropriately timing LTx-center referral. The task force has examined the most recent literature and evaluated the risk factors that continue to limit patient survival after LTx. Ideally, the objectives of LTx are to prolong life while improving quality of life. The guidelines developed by the task force apply to a limited resource and are consistent with the ethical principles described below.

[Spontaneous pneumomediastinum]. / Pneumomédiastin spontané.

INTRODUCTION: Pneumomediastinum, which can be spontaneous or secondary, is defined by the presence of free air in the mediastinum as shown on a chest X-ray and/or chest CT, with or without subcutaneous emphysema. Secondary pneumomediastinum develops in various contexts (thoracic traumatism, perforation of central airway or digestive tract, pneumothorax, barotraumatism complicating mechanical ventilation…). Spontaneous pneumomediastinum , which will be the focus of this review, develops without any of the above-mentioned conditions. STATE OF ART: Spontaneous pneumomediastinum is a rare entity which usually occurs in young people either without medical history or with an history of asthma. A trigger event is detected in 40% to 60% of cases. Positive diagnosis is made on chest radiographt but thoracic CT is more sensitive. Distinction between spontaneous pneumomediastinum and secondary pneumomediastinum is in general easy but may sometimes be more difficult, particularly in case of oesophageal perforation. The evolution of spontaneous pneumomediastinum is most often benign but, rare complications may occur. Management is most often conservative. PERSPECTIVES: There is no consensual management of spontaneous pneumediastinum because of the lack of randomized prospective studies. This may be explained by the rarity of the disease. The actual trend is to offer to the patients a conservative treatment, which could be ambulatory in some cases. CONCLUSIONS: Spontaneous pneumomediastinum is a rare entity developing mainly in young subjects. The evolution is in general benign, justifying a conservative approach.

RADIORYTHMIC: Phase III, Opened, Randomized Study of Postoperative Radiotherapy Versus Surveillance in Stage IIb/III of Masaoka Koga Thymoma after Complete Surgical Resection.

INTRODUCTION: Thymomas are rare intrathoracic malignancies that may be aggressive and difficult to treat. Knowledge and level of evidence for treatment strategies are mainly based on retrospective studies or expert opinion. Currently there is no strong evidence that postoperative radiotherapy after complete resection of localized thymoma is associated with survival benefit in patients. RADIORYTHMIC is a phase III, randomized trial aiming at comparing postoperative radiotherapy versus surveillance after complete resection of Masaoka-Koga stage IIb/III thymoma. Systematic central pathologic review will be performed before patient enrollment as per the RYTHMIC network pathway. PATIENTS AND METHODS: Three hundred fourteen patients will be included; randomization 1:1 will attribute either postoperative radiotherapy (50-54 Gy to the mediastinum using intensity-modulated radiation therapy or proton beam therapy) or surveillance. Stratification criteria include histologic grading (thymoma type A, AB, B1 vs B2, B3), stage, and delivery of preoperative chemotherapy. Patient recruitment will be mainly made through the French RYTHMIC network of 15 expert centers participating in a nationwide multidisciplinary tumor board. Follow-up will last 7 years. The primary endpoint is recurrence-free survival. Secondary objectives include overall survival, assessment of acute and late toxicities, and analysis of prognostic and predictive biomarkers. RESULTS: The first patient will be enrolled in January 2021, with results expected in 2028.

[Early outcomes following lung transplantation in patients aged 65 years and older]. / Résultats précoces de la transplantation pulmonaire chez les patients âgés de 65 ans et plus.

INTRODUCTION: The number of lung transplantations performed is increasing worldwide. With an improved experience and outcomes, the age of the recipient on its own has ceased to be an absolute contra-indication. We report our first experience with lung transplantation in patients aged 65 years or older. METHODS: From January 2014 to March 2019, the files of patients aged 65 years or older undergoing lung transplantation were retrospectively reviewed. RESULTS: During the study period, 241 patients underwent lung transplantation in Bichat hospital (Paris, France), including 25 recipients aged 65 years or older. Underlying diagnoses were interstitial (72%) and obstructive (28%) disease. The rate of single lung transplantation was 80%. Sixteen patients required ECMO assistance during the procedure. Early complications were mostly grade III primary graft dysfunction (12%) and cellular rejection (20%). Overall one-year survival rate was 76%. CONCLUSION: After a careful selection of the recipients, the early results of our retrospective single center series are encouraging. We continue to consider lung transplantation in rigorously selected recipients of aged 65 years and more.

[Stereotaxic radiotherapy of primary extracranial tumors]. / Radiothérapie stéréotaxique des tumeurs primitives extracrâniennes.

Stereotactic radiotherapy is a fundamental change from the conventional fractionated radiotherapy and represents a new therapeutic indication. Stereotactic radiotherapy is now a standard of care for inoperable patients or patients who refuse surgery. The results are encouraging with local control and survival rates very high in selected populations. The rate of late toxicity remains acceptable. Good tolerability makes it appropriate even for elderly and frail patients. In these fragile patients or in certain specific clinical situations, different surgical, radiotherapy or interventional radiology attitudes can be discussed on a case-by-case basis. These situations are considered in this article for the pulmonary, hepatic and prostatic localizations.

Acute Kidney Injury After Lung Transplantation: Perioperative Risk Factors and Outcome.

BACKGROUND: Acute kidney injury (AKI) is associated with increased short-term and long-term mortality and morbidity after lung transplantation (LT). The primary objective of this study was to analyze the perioperative factors associated with AKI according to Kidney Disease: Improving Global Outcome (KDIGO) criteria during hospitalization in an intensive care unit (ICU) after LT. METHODS: This was a single-center, observational, prospective study. AKI was defined according to KDIGO criteria. Results are expressed as median, interquartile range, absolute numbers, and percentages. Statistical analyses were performed using χ2 test, Fisher exact test, and Mann-Whitney U test. P < .05 was considered to be significant. Multivariate analysis was performed to identify independent risk factors. RESULTS: Between January 2016 and April 2018, 94 patients underwent LT (70% bilateral LT). AKI occurred during ICU stay in 46 patients (49%). KDIGO 1 AKI was observed in 16 patients (17%), KDIGO 2 in 14 patients (15%), and KDIGO 3 in 16 patients (17%), including 12 patients (75%) who required renal replacement therapy. AKI occurred before the fifth day after surgery for 38 patients (82% of the AKI patients). On multivariate analysis, independent factors associated with AKI were bilateral LT and mechanical ventilation >3 days (odds ratio [OR] 4.26, 95% confidence interval [CI] [1.49; 13.63] P = .010 and OR 5.56 [1.25; 11.47] P = .018, respectively). AKI and the need for renal replacement therapy were significantly associated with ICU mortality, 28-day mortality, and 1-year mortality. CONCLUSION: AKI is common during ICU stay after LT, especially after bilateral LT, and is associated with prolonged mechanical ventilation and increased short-term and long-term mortality.

[Current knowledge on perioperative treatments of non-small cell lung carcinomas]. / Traitements péri-opératoires des carcinomes bronchiques non à petites cellules.

Surgery is still the main treatment in early-stage of non-small cell lung cancer with 5-year survival of stage IA patients exceeding 80%, but 5-year survival of stage II patients rapidly decreasing with tumor size, N status, and visceral pleura invasion. The major metastatic risk in such patients has supported clinical research assessing systemic or loco-regional perioperative treatments. Modern phase 3 trials clearly validated adjuvant or neo-adjuvant platinum-based chemotherapy in resected stage I-III patients as a standard treatment of which value has been reassessed several independent meta-analyses, showing a 5% benefit in 5y-survival, and a decrease of the relative risk for death around from 12 to 25%. Conversely perioperative treatments were not validated for stage IA and IB patients. In more advanced stage patients, neo-adjuvant radio-chemotherapy has not been validated either. Adjuvant radiotherapy for N2 patients is currently tested in the large international phase 3 trial Lung-ART/IFCT-0503. The development of video-assisted thoracic surgery (VATS) has helped adjuvant chemotherapies for elderly patients. Perioperative targeted treatments in NSCLC with EGFR or ALK molecular alterations is currently assessed in the U.S. ALCHEMIST prospective trial. Finally, the role of immune check-points inhibitors is currently evaluated in a large international phase 3 trial testing adjuvant anti-PD-L1 monoclonal antibody, the BR31/IFCT-1401 trial, while a proof-of principle neo-adjuvant trial IONESCO/IFCT-1601, has just begun by the end of the 2016 year, with survival results of both trials expected in 5 to 7 years.

Prognostic factors after surgical resection of N1 non-small cell lung cancer.

OBJECTIVES: Non-small cell lung carcinoma (NSCLC) with N1 involvement is associated with 5-year survival rates ranging from 7% to 55%. Numerous factors have been independently reported to explain this heterogeneous prognosis, but their relative weight on long-term survival is unknown. METHODS: Patients who underwent surgical resection for NSCLC in two French centers from 1993 to 2010 were prospectively recorded and retrospectively reviewed. The overall survival (OS) of patients undergoing first-line surgery for pN1 disease was analyzed according to the type of extension, number of metastatic LN, number and anatomic location of metastatic stations. RESULTS: The study group included 450 patients (male 80.2%, mean age 63.3 ± 9.9 years, 5-year overall survival 46%). The number of metastatic station was 1 in 340 (75.6%, single-station disease) and ≥2 in 110 patients (24.4%, multi-station disease). The number of metastatic stations was correlated with the number of metastatic LN (p < .001), and associated with adverse OS (p = .0014). The presence of intralobar metastatic LN (station 12-13-14) was associated with a mechanism of direct extension (p < .001), but did not impact OS (p = .71). The location of metastatic stations was of prognostic significance only in case of multi-station disease, with hilar (station 10) involvement being associated with adverse OS (p = .005). The 110 patients with multi-station pN1 disease and the 134 patients operated on for single-station pN0N2 (skip-N2) disease during the study period yield comparable outcome (p = .52). CONCLUSIONS: In patients with resected pN1 NSCLC, the number of metastatic stations and their location in case of multi-station disease have a prognostic value.