Abdominal Complications After Lung Transplantation in a Brazilian Single Center.

Surgical and nonsurgical abdominal complications have been described after lung transplantation. However, there is limited data on this event in this population. The objective of this study was to analyze the incidence of abdominal complications in patients undergoing lung transplantation at the Heart Institute of the Faculty of Medicine, University of São Paulo (InCor-HCFMUSP) between the years 2003 and 2016. The main causes of abdominal complications were inflammatory acute abdomen (7 patients; 14%), obstructive acute abdomen (9 patients; 18%), gastroparesis (4 patients; 8%), distal intestinal obstruction syndrome (4 patients; 8%), perforated acute abdomen (7 patients; 14%), cytomegalovirus (CMV; 6 patients; 12%), and other reasons (12 patients; 26%). Separating these patients according to Clavien-Dindo classification, we had 21 patients (43%) with complications grade II, 4 patients (8%) with complications grade IIIa, 7 patients (14%) with grade IIIb complications, 7 patients (14%) with grade IV complications, and 10 patients (21%) with grade complications V. In conclusion, abdominal disorders are seriously increased after lung transplantation and correlate with a high mortality. Early abdominal surgical complication has worse prognosis.

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.

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.

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 donor's 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.

Lung transplantation in patients with cystic fibrosis.

Cystic fibrosis (CF) an autosomal recessive genetic disorder, affects many organs. The great majority of deaths occur due to respiratory failure after many years of chronic pulmonary infection. Despite recent progress in early detection by studies of genetic mutations and better understanding to treat nutritional and infectious states, lung transplantation is the CF treatment for most advanced cases. According to the International Society for Heart and Lung Transplantation (ISHLT) data, CF is the third most common reason for lung transplantation (16.8%) showing the best survival rate (60% at 5 years). We have described our experience in lung transplantation of CF patients between January 2000 and December 2011, reviewing medical charts of these patients were for gender, age, body mass index (BMI), comorbidities, disease duration, previous sputum gram stain, ischemic time, incidence of severe primary graft dysfunction (PGD Grade 3), intensive care unit (ICU) length of stay, and Kaplan-Meier survival. Among 150 lung transplantation, the 30 CF patients (20%) represented the second most common cause. The average age was 27.4 ± 9.2 years, with a slight predominance of males (n = 16; 53.3%). The average BMI was 18.9 ± 2.6. Most patients (60%) had pancreatic exocrine dysfunction. Also, 83.3% of patients showed a positive sputum culture for Pseudomonas, while Burkholderia cepacia was identified in only 4 patients (13.3%). The average time of the disease was 20.8 ± 9.7 years. All transplantation were bilateral with an average ischemic time of 472 ± 98.3 minutes and ICU length of stay of 9.9 ± 6.3 days. The survival rates at 1 and 5 years were 92% and 77%, respectively, corresponding to the best outcomes among underlying diseases, comparable with other worldwide series and better than the ISHLT reports. CF, the second most common cause for lung transplantation among our cases, showed the best survival rate among all causes. Our survival rate was comparable with other reports.

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.

Effect of methylprednisolone on perivascular pulmonary edema, inflammatory infiltrate, VEGF and TGF-beta immunoexpression in the remaining lungs of rats after left pneumonectomy

Pneumonectomy is associated with high rates of morbimortality, with postpneumonectomy pulmonary edema being one of the leading causes. An intrinsic inflammatory process following the operation has been considered in its physiopathology. The use of corticosteroids is related to prevention of this edema, but no experimental data are available to support this hypothesis. We evaluated the effect of methylprednisolone on the remaining lungs of rats submitted to left pneumonectomy concerning edema and inflammatory markers. Forty male Wistar rats weighing 300 g underwent left pneumonectomy and were randomized to receive corticosteroids or not. Methylprednisolone at a dose of 10 mg/kg was given before the surgery. After recovery, the animals were sacrificed at 48 and 72 h, when the pO2/FiO2 ratio was determined. Right lung perivascular edema was measured by the index between perivascular and vascular area and neutrophil density by manual count. Tissue expression of vascular endothelial growth factor (VEGF) and transforming growth factor-beta (TGF-β) were evaluated by immunohistochemistry light microscopy. There was perivascular edema formation after 72 h in both groups (P = 0.0031). No difference was observed between operated animals that received corticosteroids and those that did not concerning the pO2/FiO2 ratio, neutrophil density or TGF-β expression. The tissue expression of VEGF was elevated in the animals that received methylprednisolone both 48 and 72 h after surgery (P = 0.0243). Methylprednisolone was unable to enhance gas exchange and avoid an inflammatory infiltrate and TGF-β expression also showed that the inflammatory process was not correlated with pulmonary edema formation. However, the overexpression of VEGF in this group showed that methylprednisolone is related to this elevation.

Effect of methylprednisolone on perivascular pulmonary edema, inflammatory infiltrate, VEGF and TGF-beta immunoexpression in the remaining lungs of rats after left pneumonectomy.

Pneumonectomy is associated with high rates of morbimortality, with postpneumonectomy pulmonary edema being one of the leading causes. An intrinsic inflammatory process following the operation has been considered in its physiopathology. The use of corticosteroids is related to prevention of this edema, but no experimental data are available to support this hypothesis. We evaluated the effect of methylprednisolone on the remaining lungs of rats submitted to left pneumonectomy concerning edema and inflammatory markers. Forty male Wistar rats weighing 300 g underwent left pneumonectomy and were randomized to receive corticosteroids or not. Methylprednisolone at a dose of 10 mg/kg was given before the surgery. After recovery, the animals were sacrificed at 48 and 72 h, when the pO(2)/FiO(2) ratio was determined. Right lung perivascular edema was measured by the index between perivascular and vascular area and neutrophil density by manual count. Tissue expression of vascular endothelial growth factor (VEGF) and transforming growth factor-beta (TGF-ß) were evaluated by immunohistochemistry light microscopy. There was perivascular edema formation after 72 h in both groups (P = 0.0031). No difference was observed between operated animals that received corticosteroids and those that did not concerning the pO(2)/FiO(2) ratio, neutrophil density or TGF-ß expression. The tissue expression of VEGF was elevated in the animals that received methylprednisolone both 48 and 72 h after surgery (P = 0.0243). Methylprednisolone was unable to enhance gas exchange and avoid an inflammatory infiltrate and TGF-ß expression also showed that the inflammatory process was not correlated with pulmonary edema formation. However, the overexpression of VEGF in this group showed that methylprednisolone is related to this elevation.

Recommendations for the use of extended criteria donors in lung transplantation.

Selection criteria for lung donation were based on initial experiences with lung transplantation without further studies to improve them, thereby guaranteeing the best use of donated organs. A definition of an extended criteria donor is therefore required to obtain more lungs to meet the demands of patients awaiting transplantation. Studies have been reviewed for the impact on survival and morbidity of age ranges, oxygen fraction, cause of death, smoking habits, x-ray findings, infection, hepatitis serology and non-heart-beating status, seeking to support physicians to make decisions regarding the use of marginal organs.

Ex vivo lung perfusion: early report of Brazilian experience.

INTRODUCTION: Only about 15% of the potential candidates for lung donation are considered suitable for transplantation. A new method for ex vivo lung perfusion (EVLP) can be used to evaluate and recondition "marginal," nonacceptable lungs. We have herein described an initial experience with ex vivo perfusion of 8 donor lungs deemed nonacceptable. MATERIALS AND METHODS: After harvesting, the lungs were perfused ex vivo with Steen Solution, an extracellular matrix with high colloid osmotic pressure. A membrane oxygenator connected to the circuit received gas from a mixture of nitrogen and carbon dioxide, maintaining a normal mixed venous blood gas level in the perfusate. The lungs were gradually rewarmed, reperfused, and ventilated for evaluation through analyses of oxygenation capacity, pulmonary vascular resistance (PVR), lung compliance (LC), and biopsy. RESULTS: The arterial oxygen pressure (with inspired oxygen fraction of 100%) increased from a mean of 206 mm Hg in the organ donor at the referring hospital to a mean of 498 mm Hg during the ex vivo evaluation. After 1 hour of EVLP, PVR varied from 440-1454 dynes/sec/cm(5); LC was in the range of 26-90 mL/cmH(2)O. There was no histological deterioration after 10 hours of cold ischemia and 1 hour of EVLP. CONCLUSIONS: The ex vivo evaluation model can improve oxygenation capacity of "marginal" lungs rejected for transplantation. It has great potential to increase lung donor availability and, possibly, reduce time on the waiting list.

Impact of cytomegalovirus infection in lung transplant patients under universal prophylaxis: single-center experience in Brazil.

INTRODUCTION: Cytomegalovirus (CMV) infection, a common complication in lung transplant (LT) patients, is associated with worse outcomes. Therefore, prophylaxis and surveillance with preemptive treatment is recommended. OBJECTIVES: Describe the epidemiology and impact on mortality of CMV infection in LT patients receiving CMV prophylaxis. METHODS: Single-center retrospective cohort of LT recipients from August 2003 to March 2008. We excluded patients with survival or follow-up shorter than 30 days. We reviewed medical charts and all CMV pp65 antigen results. RESULTS: Forty-seven patients met the inclusion criteria and 19 (40%) developed a CMV event: eight CMV infections, seven CMV syndromes, and 15 CMV diseases. The mean number of CMV events for each patient was 1.68 +/- 0.88. Twelve patients developed CMV events during prophylaxis (5/12 had CMV serology D+/R-). Forty-six of the 47 patients had at least one episode of acute rejection (mean 2.23 +/- 1.1). Median follow-up was 22 months (range = 3-50). There were seven deaths. Upon univariate analysis, CMV events were related to greater mortality (P = .04), especially if the patient experienced more than two events (P = .013) and if the first event occurred during the first 3 months after LT (P = .003). Nevertheless, a marginally significant relationship between CMV event during the first 3 months after LT and mortality was observed in the multivariate analysis (hazards ratio: 7.46; 95% confidence interval: 0.98-56.63; P = .052). Patients with CMV events more than 3 months post-LT showed the same survival as those who remained CMV-free. CONCLUSION: Prophylaxis and preemptive treatment are safe and effective; however, the patients who develop CMV events during prophylaxis experience a worse prognosis.

Effects of pneumonectomy on nitric oxide synthase expression and perivascular edema in the remaining lung of rats

Pneumonectomy is associated with high mortality and high rates of complications. Postpneumonectomy pulmonary edema is one of the leading causes of mortality. Little is known about its etiologic factors and its association with the inflammatory process. The purpose of the present study was to evaluate the role of pneumonectomy as a cause of pulmonary edema and its association with gas exchange, inflammation, nitric oxide synthase (NOS) expression and vasoconstriction. Forty-two non-specific pathogen-free Wistar rats were included in the study. Eleven animals died during or after the procedure, 21 were submitted to left pneumonectomy and 10 to sham operation. These animals were sacrificed after 48 or 72 h. Perivascular pulmonary edema was more intense in pneumonectomized rats at 72 h (P = 0.0131). Neutrophil density was lower after pneumonectomy in both groups (P = 0.0168). There was higher immunohistochemical expression of eNOS in the pneumonectomy group (P = 0.0208), but no statistically significant difference in the expression of iNOS. The lumen-wall ratio and pO2/FiO2 ratio did not differ between the operated and sham groups after pneumonectomy. Left pneumonectomy caused perivascular pulmonary edema with no elevation of immunohistochemical expression of iNOS or neutrophil density, suggesting the absence of correlation with the inflammatory process or oxidative stress. The increased expression of eNOS may suggest an intrinsic production of NO without signs of vascular reactivity.

Effects of pneumonectomy on nitric oxide synthase expression and perivascular edema in the remaining lung of rats.

Pneumonectomy is associated with high mortality and high rates of complications. Postpneumonectomy pulmonary edema is one of the leading causes of mortality. Little is known about its etiologic factors and its association with the inflammatory process. The purpose of the present study was to evaluate the role of pneumonectomy as a cause of pulmonary edema and its association with gas exchange, inflammation, nitric oxide synthase (NOS) expression and vasoconstriction. Forty-two non-specific pathogen-free Wistar rats were included in the study. Eleven animals died during or after the procedure, 21 were submitted to left pneumonectomy and 10 to sham operation. These animals were sacrificed after 48 or 72 h. Perivascular pulmonary edema was more intense in pneumonectomized rats at 72 h (P = 0.0131). Neutrophil density was lower after pneumonectomy in both groups (P = 0.0168). There was higher immunohistochemical expression of eNOS in the pneumonectomy group (P = 0.0208), but no statistically significant difference in the expression of iNOS. The lumen-wall ratio and pO(2)/FiO(2) ratio did not differ between the operated and sham groups after pneumonectomy. Left pneumonectomy caused perivascular pulmonary edema with no elevation of immunohistochemical expression of iNOS or neutrophil density, suggesting the absence of correlation with the inflammatory process or oxidative stress. The increased expression of eNOS may suggest an intrinsic production of NO without signs of vascular reactivity.

Bronchial complications following lung transplantation.

INTRODUCTION: Bronchial complications owing to the airway anastomosis in lung transplantation are important causes of morbidity and mortality. They occur in up to 27% of cases as defined by stenosis, necrosis, and dehiscence. Treatment depends on the type of complication. OBJECTIVE: To report our experience to treat this complication. METHODS: Between 2000 and 2007, we performed 71 lung transplants of which 36 were bilateral. The total number of anastomoses was 107:52 to the right and 55 to the left. The telescoping technique was initially used (14 initial unilateral transplants), and after October, 2003 it was changed to an end-to-end anastomosis (57 transplants and 93 anastomoses). RESULTS: Eight patients developed bronchial complications including two that were bilateral. There were 4 stenosis, 3 dehiscences, and 3 necrosis complications (9.4%). The complication rate for telescoping anastomosis was 21.4%, and for the end-to-end technique, 7.5%. The treatment of the stenosis used metallic or plastic self-expandable stents. Two bronchial dehiscences resulted in case of bronchopleural fistulae, empyema, and death; the other patient experienced spontaneous resolution. Concerning bronchial necrosis, 1 patient developed fistulization to the pulmonary artery and massive hemoptysis, and the other with bilateral necrosis, a spontaneous resolution. CONCLUSION: Our bronchial anastomosis complication rate was comparable with that in other reports. The rate for the telescoping technique was greater compared with the end-to-end technique. The treatment of bronchial stenosis with a self-expandable prosthesis showed good results.

Bilateral lung transplantation in asymmetric thorax: case reports.

Suppurative lung diseases, such as cystic fibrosis and bronchiectasis, when diffuse and associated with important functional loss, can be treated with bilateral lung transplantation with good results. These diseases are frequently associated with previous lung resections presenting an asymmetric thorax, thus making lung extraction difficult and generating disproportion between the graft and the pleural cavity. To treat this condition, pneumonectomy and single lung transplantation is a feasible option; however, there are associated comorbidities and an invariable need for extracorporeal circulation. Described herein are 2 patients with an asymmetric thorax, treated with bilateral transplantation and lung volume reduction with lobectomy.

Diagnosis and treatment of mediastinal tumors by thoracoscopy.

OBJECTIVES: Thoracoscopic management of mediastinal tumors is still subject to analysis. Seventy-three patients underwent thoracoscopy for treatment of mediastinal masses and were analyzed retrospectively in order to evaluate the effectiveness and complications of the procedure. METHODS: Between 1983 and 1999, 21 conventional thoracoscopies and 52 video-assisted thoracic surgeries were performed (33 for diagnostic purposes and 40 for therapy). Patient ages ranged from 2 to 81 years (mean, 43.8 years) with a slight predominance of girls and women over men and boys (41 vs 32, respectively). All patients underwent general anesthesia using simple intubation (22 patients) or double-lumen intubation (51 patients). RESULTS: The histologic type of tumors was obtained in all patients. For therapeutic purposes, a change of procedure to thoracotomy was necessary in nine patients. The reasons for this change were tumor size, tumor invasion of nearby structures, difficulties in continuing the dissection, the performance of an upper lobectomy, and suturing the iatrogenic lesion of the diaphragm. Four patients died during the first 30 postoperative days as a consequence of their primary pathology. CONCLUSION: Thoracoscopy was confirmed as an effective diagnostic and therapeutic alternative for the treatment of mediastinal disorders.