Metachronous Pulmonary Neoplasms in Lung Transplantation-When They Arise in the Donor Lung: A Case Report.

Lung cancer (LC) is uncommon among lung transplant recipients, being most often described in the native lung of single-lung transplant recipients. Its appearance in the transplanted lung is a very uncommon phenomenon, in which donor and recipient factors appear to be involved. We present a case of 2 distinct metachronous lung neoplasms diagnosed in the transplanted lung of a non-smoker patient with progressive massive silicosis (PMS), who underwent left unipulmonary transplantation at 39 years. The donor was a smoker and thoracic computed tomography (CT) performed before the organ collection showed no abnormalities. Thirty months after transplantation, a new node with significant avidity in positron emission tomography (PET)-CT was diagnosed in the upper left lobe (ULL). The Thoracic Surgery team chose to proceed directly to surgery with atypical resection of the nodule. Anatomopathologic study revealed an epidermoid carcinoma (pT1aNx). Multidisciplinary group decided clinical surveillance; however, 2 years later, the appearance of 2 new nodules in the ULL (PET-CT positive) was observed. It was again decided to proceed to the surgery with a second atypical resection. The anatomopathologic study of one nodule revealed pulmonary adenocarcinoma (pT1aNx), and the other was compatible with epidermoid carcinoma (pT1aNx). One month later, the patient was hospitalized with a pulmonary abscess and posteriorly developed a probable acute allograft rejection, eventually dying at the age of 44, 51 months after transplantation. This case raises relevant questions regarding the donor selection criteria and the approach to LC diagnosed in the post-transplantation period.

Prevalence and Diagnosis of Chronic Kidney Disease in Maintenance Lung Transplant Patients: ICEBERG Study.

BACKGROUND: Chronic renal dysfunction (CRD) after lung transplantation (LT) is a common and noteworthy complication associated with increased morbidity and mortality rates. The study objectives were to determine the prevalence of CRD according to different diagnostic criteria and describe its therapeutic management. METHODS: This observational, multicenter, retrospective study included LT patients with ≥ 2 years of evolution. CRD was defined according to 2 different methods: (1) by the physician's subjective clinical criteria and (2) by analytical criteria (estimated glomerular filtration rate [eGFR] by Modification of Diet in Renal Disease of ≤ 59 mL/min). RESULTS: We included 113 patients; 65.5% were men and the mean age at transplant was 49.1 (12.6) years. At 6 months after transplant, approximately half of patients had CRD according to analytical criteria, and, at 2 years after transplantation, the prevalence rose to 80%. Although clinical prevalence and analytical prevalence were similar (68.8% and 78.6%), a weak concordance was observed (Kappa index: 0.6). Among patients who were not classified as having CRD according to clinical criteria, 40.0% (14/35) were diagnosed with CRD according to analytical criteria. None of the patients underwent renal biopsy, and 5.1% of patients required dialysis. In 77.0% of patients with clinical CRD diagnosis, the immunosuppressive regimen was modified: reduction of isolated calcineurin inhibitors (CNIs) (35.0%), CNIs decreased with mycophenolic acid change (23.3%), and CNIs lowering with mammalian target of rapamycin introduction (6.7%). In a multivariate logistic regression model, the independent factors associated with CRD were an older recipient age, low body mass index (BMI) at transplant, treatment with cyclosporine/azathioprine, and low eGFR at the first month after transplant. CONCLUSIONS: We found a high incidence of CRD at the first year after transplantation, which increased subsequently. Moreover, CRD was considerably underestimated by physicians' subjective clinical criteria. End points related to CRD development were older age, low BMI, azathioprine use, and low eGFR during the first month after transplant. The latter finding provides an opportunity to implement prevention strategies.

Postoperative surgical complications after lung transplantation.

This is a review article on the main postoperative complications after lung transplantation: airways complications, vascular complications, pleural complications, surgical wound complications, and abdominal complications. Incidence data, severity, and major management regimens are reported. Postoperative complications after lung transplantation result in a significantly increased morbidity and mortality, with early diagnosis and therapy being extremely important.

WITHDRAWN:Postoperative surgical complications after lung transplantation.

This article has been withdrawn for editorial reasons because the journal will be published only in English. In order to avoid duplicated records, this article can be found at http://dx.doi.org/10.1016/j.rppnen.2014.09.007. The Publisher apologizes for any inconvenience this may cause. The full Elsevier Policy on Article Withdrawal can be found at http://www.elsevier.com/locate/withdrawalpolicy.

WITHDRAWN: The future of lung transplantation.

This article has been withdrawn for editorial reasons because the journal will be published only in English. In order to avoid duplicated records, this article can be found at http://dx.doi.org/10.1016/j.rppnen.2014.09.006. The Publisher apologizes for any inconvenience this may cause. The full Elsevier Policy on Article Withdrawal can be found at http://www.elsevier.com/locate/withdrawalpolicy.

Avances en la inmunosupresión del trasplante pulmonar / Advances in immunosuppression after lung transplantation

La inmunosupresión en el trasplante se ha modificado en los últimos años con el descubrimiento de nuevos fármacos que intentan atacar las distintas vías de la respuesta inmunológica, con la idea de conseguir una inmunosupresión más personalizada y con menores efectos secundarios. A pesar de seguir los pasos de los otros trasplantes de órganos sólidos, el trasplante pulmonar, por sus especiales características no ha conseguido similares resultados a medio y largo plazo. El mejor entendimiento de los mecanismos de rechazo, el control farmacodinámico de los fármacos, las nuevas vías de administración que disminuyan los efectos secundarios y los nuevos fármacos o procesos inmunomoduladores contribuyen a mejorar las expectativas de este trasplante en un próximo futuro (AU)

Immunosuppression in transplantation has experienced changes in recent years as a result of the introduction of new drugs that act upon the different pathways of the host immune response with the purpose of securing more individualized immune suppression, with fewer side effects. Although following in the steps of other solid organ transplant modalities, lung transplantation, because of its special characteristics, has not yielded similar middle- and long-term results. Improved understanding of the underlying rejection mechanisms, the pharmacodynamic control of drugs, new administration routes designed to reduce the side effects, and new drug substances or immune modulating processes will all contribute to improve the expectations associated to lung transplantation in the near future (AU)

Recommendations on the use of everolimus in lung transplantation.

The antiproliferative effect of everolimus provides a therapeutic option in the immunosuppression therapy of lung transplantation, by reducing both the risk of acute rejection and the process of progressive fibrosis that determines chronic graft rejection. However, few data on the use of everolimus in lung transplantation have been published to date, and the specific indications of the drug, along with the most adequate time for its introduction or dosing, have not been defined yet. The aim of this article is to propose recommendations for the use of everolimus in lung transplant recipients, including indications, dosing schedules and the use of concomitant immunosuppression. This consensus document has been developed by experts of all the Spanish lung transplant groups from the review of the existing literature and the clinical experience.

Advances in immunosuppression after lung transplantation.

Immunosuppression in transplantation has experienced changes in recent years as a result of the introduction of new drugs that act upon the different pathways of the host immune response with the purpose of securing more individualized immune suppression, with fewer side effects. Although following in the steps of other solid organ transplant modalities, lung transplantation, because of its special characteristics, has not yielded similar middle- and long-term results. Improved understanding of the underlying rejection mechanisms, the pharmacodynamic control of drugs, new administration routes designed to reduce the side effects, and new drug substances or immune modulating processes will all contribute to improve the expectations associated to lung transplantation in the near future.

A retrospective 12-month study of conversion to everolimus in lung transplant recipients.

BACKGROUND: Everolimus has potent antifibrotic effects that may potentially affect the clinical course of bronchiolitis obliterans syndrome (BOS) or provide nephroprotective immunosuppressive regimens for lung transplantation. METHODS: We retrospectively assessed the 12-month outcomes of the conversion to everolimus among lung recipients in six Spanish centers. RESULTS: From March 2005 to December 2007, 65 lung recipients who were at a mean posttransplantation time of 10.2 ± 7.9 months were converted to everolimus, mainly because of BOS (64.6%) or renal insufficiency (RI; 12.3%). The initial dose of everolimus was 1.9 ± 0.6 mg/d and the mean blood trough levels were stable over time (6.4 ± 2.8 ng/mL at 12 months). Conversion to everolimus allowed us to eliminate the calcineurin inhibitor (CNI) in 21% of patients. Among the overall population, the forced expiratory volume at 1 second (FEV(1)) and renal function remained stable. Mean FEV(1) did not change among the 35 (81%) patients surviving BOS at 12 months: preconversion FEV(1): 1.449.5 ± 641.9 mL vs 12-month FEV(1): 1420.0 ± 734.6 mL (P = .866). There was a significant improvement in renal function among the RI patients with mean glomerular filtration rates of 42.2 ± 15.2 mL/min/1.73 m(2) (P = .043) at 6 and 44.4 ± 18.8 mL/min/1.73 m(2) at 12 months, (P = .063) and a decrease in the use of CNIs from 1% of RI patients preconversion to 57% at 6 and 75% at 12 months. With a mean of 8.1- months follow-up (range: 1-31.3) overall survival was 84.6% at 1 year and 50% at 22.3 months. Progressive BOS was the main cause of death. Reasons for everolimus discontinuation were patient death (n = 10), lack of efficacy (n = 4), gastrointestinal adverse events (n = 2), and edema (n = 2). CONCLUSIONS: BOS and RI were the main indications for conversion to everolimus among lung recipients. Conversion to everolimus improved renal function among patients converted because of RI. The present results were inconclusive regarding effects of everolimus on BOS.

Influence of body mass index in the postoperative evolution after lung transplantation.

OBJECTIVE: To study the influence of body mass index (BMI) on mortality and postoperative evolution in our 10-year experience as a lung transplant group. METHODS: The study included 256 lung transplants performed between June 1999 and June 2009. BMI was stratified into 4 groups (<20 kg/m2 underweight, 20-25 normal weight, 25-30 overweight, and >30 obese) for posttransplant mortality assessment (chi-square) in relation to age, gender, pathology, and transplant type (logistic regression). Time of mechanical ventilation and length of stay in the intensive care unit and in the hospital were also analyzed (Kruskal-Wallis test). RESULTS: BMI showed a normal distribution with a mean value of 24.8±5 kg/m2 (range, 13-38). Although postoperative mortality was greater in the overweight (23%) and obese (23.7%) groups, it did not reach statistical significance, nor was there a significant increase in the risk of death (odds ratios of 1.06 and 1.17, respectively). Risk of death was independent of BMI and was associated with pathology (lower in emphysema) and transplant type (lower in single lung). There were no significant differences in duration of mechanical ventilation (342 hours in obese patients vs 180 in normal weight; P=.7), length of stay in the intensive care unit (18 days in obese patients vs 14 in normal weight; P=.8), or length of hospital stay of patients that were discharged (37 days in obese patients vs 43 in normal weight; P=.8). CONCLUSIONS: In our experience, BMI is not a risk factor that significantly increases postoperative mortality, probably owing to an adequate selection of recipients and an optimal posttransplant management. However, it must be considered to be a relative contraindication, because it is established in the international guidelines, obliging a correct assessment of patients, especially if there are other comorbidities.

Complications during clinical evolution in lung transplantation: pulmonary embolism.

BACKGROUND: Medical complications after lung transplantation (LT) are frequent despite the advances in management. The objectives of this study were to evaluate the incidence and clinical features of pulmonary embolism (PE) among LT recipients in our center. PATIENTS AND METHODS: We performed a retrospective descriptive study of 280 patients who underwent LT between June 1999 and December 2009. RESULTS: Five patients with PE (1.78%) had undergone single LT due to idiopathic pulmonary fibrosis (IPF). PE developed in the transplanted lung and was bilateral in 2 cases. The only associated risk factor was obesity in 3 patients. The clinical presentation was nonspecific; the most frequent symptom being dyspnea. Computed tomography (CT) angiography and ventilation-perfusion scan were used for diagnosis. Patients underwent treatment with low-molecular weight heparin followed by oral anticoagulation. CONCLUSIONS: Our study showed a low incidence of PE (1.78%), although we focused exclusively on this condition, excluding other entities such as deep vein thrombosis. All PE events occurred in the subpopulation of IPF transplant recipients. Possibly some factors predisposed these patients to PE, although they remain unclear. Because PE can cause significant morbidity in LT recipients, it is important to include PE in the differential diagnosis among LT patients presenting with dyspnea, hypoxia, or clinical deterioration.

Bronchoscopic lung volume reduction in a single-lung transplant recipient with natal lung hyperinflation: a case report.

After single lung transplantation for emphysema native lung hyperinflation is a common complication that may cause respiratory failure. Herein we have reported satisfactory bronchoscopic lung volume reduction in a left single-lung transplant recipient with native lung hyperinflation, who suffered from Medical Research Council (MRC) class 3 dyspnea and chest pain. Three endobronchial valves (Zephyr; Emphasys Medical, Redwood, Calif, United States) were placed into the segmental bronchi of the right upper lobe, using videobronchoscopy under general anesthesia. Postoperative chest computed tomography revealed subsegmental atelectasis in that lobe. The clinical benefit was an improved MRC dyspnea class from 3 to 2, which was still present at 4 months after the procedure, although there were no remarkable changes in spirometric parameters.

Lung transplantation as the first choice in emphysema.

INTRODUCTION: The indication for single or double lung transplantation in patients diagnosed with pulmonary emphysema is a topic of current debate. Our aim was to analyze the differences in the incidence of perioperative complications, survival, and quality of life between single and double lung transplantations. MATERIALS AND METHODS: From 1999 to 2008, 223 subjects underwent transplantation in our department, of whom 62 (28%) had a previous diagnosis of pulmonary emphysema. A retrospective study was performed to establish possible differences between group 1 (single lung) and group 2 (double lung) transplants analyzing overall survival using the Kaplan-Meier method and differences between groups using the log-rank test. Pearson chi-square test was used to compare the frequency of postoperative complications, bronchiolitis obliterans BOS acute rejection episodes, and infections. RESULTS: We included 62 patients who underwent transplantation for emphysema. Cumulative 5-year survival rate, excluding preoperative mortality, was 54% overall, 59% for group 1, and 56% for group 2. No significant differences were observed between the groups (P = .47). The frequency of BOS was 34% in group 1 and 42% in group 2 (P = .52). At least 1 acute rejection episode occurred in 52% of group 1 patients and 51% of group 2 patients (P = .98). Bacterial infections were experienced by 50% of group 1 patients and 54% of group 2 patients (P = .72). Fungal infections affected 10% of group 1 patients and 15% of group 2 patients (P = .71). Intraoperative complications were recorded in 27.6% of group 1 patients versus 54% of group 2 patients, a difference that was statistically significant (P = .032). CONCLUSIONS: The study results supported the decision of our group to consider single lung transplantation the treatment of choice in emphysema, which may be complemented with volume reduction surgery in the native lung or subsequent transplantation of the contralateral lung.

Results of "twinning procedure" in lung transplantation: experience in a single center.

INTRODUCTION: The major limiting factor for lung transplantation (LT), both worldwide and in Spain, is the number of suitable lung donors. This, together with the increased demand for LT, led us to propose the performance of 2 single lung transplantations simultaneously using the same donor (the "twinning procedure"). OBJECTIVE: The objective of this study was to analyze the outcome of patients who underwent transplantation with this procedure, assessing differences between the first and the second transplant. PATIENTS AND METHODS: From November 2001 to August 2008, 46 single lung transplantations (SLTs) were performed with 23 donors. RESULTS: The mean ischemia time was 258 minutes (median, 265) for the first transplantation and 312 minutes (median, 320) for the second transplantation. Primary graft dysfunction occurred in 5 patients (24%) in the first group and 9 in the second group (39%; P = .27). The median intubation time was 8 hours for the first and 6.5 hours for the second group. The mean hospital stay was 39 and 31 days, respectively. Postoperative mortality was 2 (8.7%) and 3 (13%) patient, respectively (P = .99). There was no significant difference in the incidence of acute rejection episodes, infections, or chronic rejections. Five-year survival rates were 67.9% for the first and 61.5% for the second (Kaplan-Meier). CONCLUSIONS: The performance of 2 SLTs using the same donor and in the same hospital was feasible with adequate planning, permitting better use of donors and reducing waiting list time and mortality. Our results showed no increased risk for recipients of the second transplant in the early postoperative and long-term periods.

Reoperation in the postoperative period of lung transplantation.

BACKGROUND: Lung transplantation (LTx) has been established as the last treatment option in certain lung diseases. It is not uncommon for complications to occur that require urgent reoperation. The objective of our study was to analyze the characteristics of lung transplant patients who required reoperation in the postoperative period. PATIENTS AND METHODS: We have conducted a retrospective descriptive study of 224 lung transplants from January 1999 to September 2008, excluding retransplants. A subgroup of 16 subjects (7.2%) required reoperations. RESULTS: These 16 individuals had a mean age of 49.38 +/- 14.32 years with 75% men and 25% women. The disease leading to LTx was emphysema in 6 (37.5%), pulmonary fibrosis in 5 (31.3%), pulmonary hypertension in 2 (12.5%) and bronchiectasis, cystic fibrosis, and lymphangioleiomyomatosis in 1 each (6.3%). Preoperatively, 40% were taking corticosteroids. Double lung transplantation was performed in 56.3% and single lung in 43.7%. LTx surgery was prolonged in 68.8% of patients and intraoperative complications were more frequent than in the other patients (P = .041). The causes for reoperation were bleeding in 13 (of these, 5 had severe adhesions and 4 required extracorporeal circulation during LTx); bronchial dehiscence in 1; wall dehiscence in 1; and vascular stenosis in 1. At the end of the study, 62.5% were alive and among the 6 who died, 3 succumbed as a result of the surgery. Most subjects underwent late reoperation after a mean of 16 days from transplantation (range, 1-55). The need for reoperation was not associated with greater perioperative mortality. CONCLUSIONS: The incidence of reoperation in the postoperative period was low in our series. The main cause was bleeding. In more than half of the cases, LTx surgery was prolonged and intraoperative complications were more frequent. The need for reoperation was not associated with greater perioperative mortality.

A multicenter study of valganciclovir prophylaxis up to day 120 in CMV-seropositive lung transplant recipients.

Seventy-six cytomegalovirus (CMV)-seropositive lung transplant recipients receiving valganciclovir (900 mg/day) for CMV prophylaxis were compared with a group of 87 patients receiving oral ganciclovir (3000 mg/day). Prophylaxis was administered to day 120 post-transplantation and follow-up was 1 year. In addition, a study was conducted on risk factors for CMV infection/disease. CMV disease incidence was 7.9% and 16.1% for valganciclovir and oral ganciclovir, respectively (p = 0.11). Patients receiving valganciclovir had fewer viral syndromes (2.6% vs. 11.5%, p < 0.05), a similar rate of tissue-invasive disease (5.2% vs. 4.6%, p = ns), longer time-to-onset of CMV infection/disease (197.5 vs. 155.2 days, p < 0.05), and a lower probability of infection/disease while on prophylaxis (1.3% vs. 12.6%, p < 0.01). Nonetheless, leukopenia incidence was higher with valganciclovir (15.8% vs. 2.3%, p < 0.01), as was the need for treatment withdrawal due to adverse effects (11.8% vs. 1.1%, p < 0.01). CMV infection was similar in both groups (32.9% vs. 34.5%). Induction therapy with basiliximab and glucocorticosteroid treatment were independent risk factors for developing CMV infection/disease. In conclusion, valganciclovir prophylaxis results in a low incidence of CMV disease in lung transplant recipients and appears more effective than oral ganciclovir. Despite the comparatively higher incidence of adverse events with valganciclovir, the drug can be considered safe for prophylaxis.

Efficiency and safety of inhaled amphotericin B lipid complex (Abelcet) in the prophylaxis of invasive fungal infections following lung transplantation.

BACKGROUND: Invasive fungal infections (IFIs) in patients undergoing lung transplantation (LT) are associated with significant mortality. Previous studies have shown the efficacy of aerosolized amphotericin B deoxycholate and oral fluconazole for antifungal prophylaxis. Evolving data show a potential advantage of prophylaxis with lipid-based formulations of amphotericin B in the prevention of IFIs. We reviewed the incidence of IFIs among patients receiving aerosolized amphotericin B lipid complex (ABLC) in LT. METHODS: We undertook a retrospective review of the results of our antifungal protocol in a cohort of 60 LT patients. We analyzed the efficiency, safety, and tolerability of 50 mg of aerosolized ABLC administered postoperatively for IFI prophylaxis once every 2 days for 2 weeks and then once per week for at least 13 weeks. In addition, these transplanted patients received fluconazole (200 mg/d) during the first 21 days posttransplant. The prophylaxis-related efficiency and safety were quantified for IFIs and adverse events (AEs) for 6 months after study drug initiation. RESULTS: Prophylaxis was efficient in 59 (98.3%) patients. Only one patient developed a possible IFI, due to Aspergillus fumigatus. Four patients presented nausea and vomiting as an AE, although aerosolized amphotericin B was ongoing. CONCLUSIONS: Nebulized ABLC was effective, safe, and well tolerated for the prophylaxis of aspergillosis in lung transplant patients during the early posttransplant period.