P.M. Pêgo-Fernandes

Risk Factors and Survival Impact of Primary Graft Dysfunction After Lung Transplantation in a Single Institution

BACKGROUND Lung transplantation has become a standard procedure for some end-stage lung diseases, but primary graft dysfunction (PGD) is an inherent problem that impacts early and late outcomes. The aim of this study was to define the incidence, risk factors, and impact of mechanical ventilation time on mortality rates among a retrospective cohort of lung transplantations performed in a single institution. METHODS We performed a retrospective study of 118 lung transplantations performed between January 2003 and July 2010. The most severe form of PGD (grade III) as defined at 48 and 72 hours was examined for risk factors by multivariable logistic regression models using donor, recipient, and transplant variables. RESULTS The overall incidence of PGD at 48 hours was 19.8%, and 15.4% at 72 hours. According multivariate analysis, risk factors associated with PGD were donor smoking history for 48 hours (adjusted odds ratio [OR], 4.83; 95% confidence interval [CI], 1.236-18.896; P = .022) and older donors for 72 hours (adjusted OR, 1.046; 95% CI, 0.997-1.098; P = .022). The operative mortality was 52.9% among patients with PGD versus 20.3% at 48 hours (P = .012). At 72 hours, the mortality rate was 58.3% versus 21.2% (P = .013). The 90-days mortality was also higher among patients with PGD. The mechanical ventilation time was longer in patients with PGD III at 48 hours namely, a mean time of 72 versus 24 hours (P = .001). When PGD was defined at 72 hours, the mean ventilation time was even longer, namely 151 versus 24 hours (P < .001). The mean overall survival for patients who developed PGD at 48 hours was 490.9 versus 1665.5 days for subjects without PGD (P = .001). Considering PGD only at 72 hours, the mean survival was 177.7 days for the PGD group and 1628.9 days for the other patients (P < .001). CONCLUSION PGD showed an important impacts on operative and 90-day mortality rates, mechanical ventilation time, and overall survival among lung transplant patients. PGD at 72 hours was a better predictor of lung transplant outcomes than at 48 hours. The use of donors with a smoking history or of advanced age were risk factors for the development of PGD.

Posterior reversible encephalopathy syndrome in lung transplantation: 5 case reports.

Posterior reversible encephalopathy syndrome (PRES) is a cliniconeuroradiologic entity characterized by typical neurologic symptoms with characteristic cerebral image alterations. It has been reported in solid organ transplantations, especially related to the use of calcineurin inhibitors. The incidence of PRES in lung transplantation is unknown and probably under-reported in the literature. Here we describe 5 cases of PRES after bilateral lung transplantation. One of the reported cases was the first in the literature in which the neurologic onset precluded the introduction of calcineurin inhibitor. Therefore, although calcineurin inhibitors are known to play an important role in the development of PRES in the setting of lung transplantation, other causes seems to be involved in the physiopathology of this syndrome.

Fungal infection by Mucorales order in lung transplantation: 4 case reports.

Mucorales is a fungus that causes systemic, highly lethal infections in immunocompromised patients. The overall mortality of pulmonary mucormycosis can reach 95%. This work is a review of medical records of 200 lung transplant recipients between the years of 2003 and 2013, in order to identify the prevalence of Mucorales in the Lung Transplantation service of Heart Institute (InCor), Hospital das Clínicas da Universidade de São Paulo, Brazil, by culture results from bronchoalveolar lavage and necropsy findings. We report 4 cases found at this analyses: 3 in patients with cystic fibrosis and 1 in a patient with bronchiectasis due to Kartagener syndrome. There were 2 unfavorable outcomes related to the presence of Mucorales, 1 by reduction of immunosuppression, another by invasive infection. Another patient died from renal and septic complications from another etiology. One patient was diagnosed at autopsy just 5 days after lung transplantation, with the Mucor inside the pulmonary vein with a precise, well-defined involvement only of donors segment, leading to previous colonization hypothesis. There are few case reports of Mucorales infection in lung transplantation in the literature. Surveillance for the presence of Mucor can lead to timely fungal treatment and reduce morbidity and mortality in the immunocompromised patients, especially lung transplant recipients.

Stents for Bronchial Stenosis After Lung Transplantation: Should They Be Removed?

BACKGROUND Airway complications after lung transplantation are the major cause of morbidity, affecting up to 33% of all cases. Bronchial stenosis is the most common complication. The use of stents has been established as the most effective therapy; however, their removal is recommended after 3-6 months of use. We have been using self-expandable stents as a definitive treatment and remove them only if necessary. For this report, we evaluated the use of self-expandable stents as a definitive treatment for bronchial stenosis after lung transplantation. METHODS We performed a retrospective cohort study to evaluate patients with bronchial stenosis from August 2003 to April 2014. Clinical and pulmonary function test data were collected. RESULTS Two hundred lung transplants were performed, 156 of which were bilateral. Sixteen patients experienced airway complications: 4 had dehiscence, 2 necrosis, and 10 bronchial stenosis. Of these patients, 7 had undergone bilateral procedures, and 2 patients developed stenosis in both sides. Twelve anastomotic stenoses were observed. The follow-up after stenting ranged from 1 to 7 years. All patients had increased lung function, and 4 remained stable with sustained increase in pulmonary function without episodes of infection. Three patients required removal of their prosthesis 6 months to 1 year after implantation because of complications. Two patients died owing to unrelated causes. CONCLUSIONS Definitive treatment of bronchial stenosis with self-expandable stents is a viable option. The 1st year seems to be the most crucial for determining definitive treatment, because no patients required removal of their stent after 1 year.

Endobronchial ultrasound-guided transbronchial needle aspiration for lung cancer staging: early experience in Brazil,

Objective: Endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) is a minimally invasive, safe and accurate method for collecting samples from mediastinal and hilar lymph nodes. This study focused on the initial results obtained with EBUS-TBNA for lung cancer and lymph node staging at three teaching hospitals in Brazil. Methods: This was a retrospective analysis of patients diagnosed with lung cancer and submitted to EBUS-TBNA for mediastinal lymph node staging. The EBUS-TBNA procedures, which involved the use of an EBUS scope, an ultrasound processor, and a compatible, disposable 22 G needle, were performed while the patients were under general anesthesia. Results: Between January of 2011 and January of 2014, 149 patients underwent EBUS-TBNA for lymph node staging. The mean age was 66 ± 12 years, and 58% were male. A total of 407 lymph nodes were sampled by EBUS-TBNA. The most common types of lung neoplasm were adenocarcinoma (in 67%) and squamous cell carcinoma (in 24%). For lung cancer staging, EBUS-TBNA was found to have a sensitivity of 96%, a specificity of 100%, and a negative predictive value of 85%. Conclusions: We found EBUS-TBNA to be a safe and accurate method for lymph node staging in lung cancer patients.

Tracheal transplantation: is there lumen at the end of the tunnel?

th and early 20 th century. 2 Since then, a large number of surgical approaches for tracheal transplantation have been tried, with poor results. 2 In spite of some anecdotal reports, no clinically useful standard approach for tracheal transplantation has yet been achieved, and this remains under investigation. The development of a clinically useful approach relies on both a technically simpler way for tracheal graft vascu larization, and the avoidance of post-transplantation immunosuppressive therapy. Recently, tracheal graft vascularization with topically-applied angiogenic factors has been reported. 3 The use of angiogenic factors could obviate the need for complex surgical procedures for tracheal vascularization. Moreover, the recently described reepithelialization phenomena, and reports on improvements through tissue-engineering techniques, have raised the possibility of abbreviated or even absence of post-transplantation immunosuppressive therapy. 4,5

Incidence and Mortality by Cancer in Patients After Lung Transplantation in a Brazilian Institution

BACKGROUND The first human lung transplantation was performed by James Hardy in 1963 due to lung cancer. Currently, malignancy has its importance in the follow-up of transplanted patients because cancer risk is higher in this population and the main risk factor for this augmentation is immunosuppression. The most common types of cancer are non-melanoma skin cancer and post-transplantation lymphoproliferative diseases. The objective of this study is to measure the cancer incidence and its related mortality in lung-transplanted patients of a Brazilian institution. METHODS Review of the records of the 263 patients who underwent lung transplantation between April 2000 and April 2016 at the Heart Institute (InCor), focusing on the incidence of cancer, most common types of malignancies, and cancer mortality rate. We compared incidence and mortality with the International Society for Heart and Lung Transplantation (ISHLT) database. RESULTS During the 16-year period, the total incidence of cancer was 10.3% with 27 cases diagnosed in 21 patients. The most common types of cancer were non-melanoma skin cancer, prostate cancer, and post-transplantation lymphoproliferative diseases. Comparing the incidences after 1-year, 5-year, and 10-year follow-up with the ISHLT database, they were similar in the first two periods and higher in the third period. As to cancer mortality rate, it was similar to the ISHLT database in both periods analyzed. CONCLUSION The incidence of malignancies was higher in our transplanted patients in comparison with the Brazilian population, and the most frequent types of cancer are in accordance with the literature, except for prostate cancer. Cancer mortality rate was similar to that from the ISHLT database.

Histopathological Findings Associated With Gastroesophageal Reflux Disease and Aspiration After Lung Transplantation: Initial Brazilian Single-Center Experience

BACKGROUND Gastro-esophageal reflux disease (GERD) and broncho-aspiration (BA) are known to increase the risk for chronic lung allograft dysfunction (CLAD). However, specific lung injury mechanisms are not clearly known. The objective of the study was to describe histopathological findings in surveillance lung transbronchial biopsies that can be correlated with episodes of BA in the lung allograft. METHODS This retrospective analysis of surveillance transbronchial biopsies was performed in lung transplant recipients, with available data of broncho-alveolar fluid (cultures and cytology), lung function parameters, and esophageal functional tests. RESULTS Were analyzed 11 patients, divided into 3 groups: (1) GERD group: 4 patients with GERD and CLAD diagnosis; (2) control group: 2 patients without GERD or CLAD; and (3) BA group: 5 patients with foreign material in lung biopsies. A histopathological pattern of neutrophilic bronchitis (NB) was present in 4 of 4 cases in the GERD group and in 1 of 5 cases in the BA group in 2 or more biopsy samples; culture samples were all negative; the 5 NB-positive patients developed CLAD and died (3/5) or needed re-transplantation (2/5). The other 3 patients in the BA group had GERD without NB or CLAD. Both patients in the control group had transient NB in biopsies with positive cultures but remained free of CLAD. CONCLUSIONS Surveillance transbronchial biopsies may provide useful information other than the evaluation of acute cellular rejection and can help to identify high-risk patients for allograft dysfunction related to gastro-esophageal reflux.