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• W2034290274 abstract "Lung transplantation has become an accepted treatment modality for patients with advanced lung disease. Despite two decades of experience, limited long-term survival, caused predominantly by the development of chronic allograft rejection and infection, remains the main shortcoming of lung transplantation. However, recent reports from large transplant centers and the International Heart and Lung Transplant Registry reveal improving survival in lung transplant recipients.1Christie JD Edwards LB Aurora P et al.Registry of the International Society for Heart and Lung Transplantation: twenty-fifth official adult lung and heart/lung transplantation report–2008.J Heart Lung Transplant. 2008; 27: 957-969Abstract Full Text Full Text PDF PubMed Scopus (180) Google Scholar Data also show a progressive increase in the mean age of lung transplant recipients with chronic obstructive pulmonary disease (COPD) and pulmonary fibrosis as the two main indications of lung transplantation. All of these trends are expected to result in a higher rate of medical complications in transplant recipients, particularly the development of malignancy. Malignancy has long been observed as a complication of chronic immunosuppressive therapy in organ transplant recipients. Dysregulation of antitumor immune surveillance, pretransplant environmental exposures such as tobacco smoke and sunlight, and a variety of viral infections are the main underlying mechanisms contributing to the development of malignancy. The cumulative risk of developing one or more malignancy, excluding nonmelanoma skin cancer, in transplant recipients with a functional graft is nearly 30% after 20 years.2Buell JF Gross TG Woodle ES Malignancy after transplantation.Transplantation. 2005; 80: S254-S264Crossref PubMed Scopus (446) Google Scholar Skin cancer and lymphoproliferative disorders are the most frequent types of posttransplant malignancy, irrespective of the transplanted organ type. However, a wide variety of cancers may develop with specific differences existing based on type of transplant, characteristics of the patient population, and risk factors. In this context, bronchogenic carcinoma is pertinent in recipients of lung transplantation. In the general population, bronchogenic carcinoma is the leading cause of cancer-related mortality both in men and women. Initial reports, mainly from renal transplant recipients, have not revealed a significantly higher incidence of bronchogenic carcinoma compared with the general population. However, more recent studies, and particularly studies in thoracic organ transplant recipients show a drastically higher incidence in this patient cohort.3Roithmaier S Haydon AM Loi S et al.Incidence of malignancies in heart and/or lung transplant recipients: a single-institution experience.J Heart Lung Transplant. 2007; 26: 845-849Abstract Full Text Full Text PDF PubMed Scopus (82) Google Scholar Indeed, Roithmaier et al.3Roithmaier S Haydon AM Loi S et al.Incidence of malignancies in heart and/or lung transplant recipients: a single-institution experience.J Heart Lung Transplant. 2007; 26: 845-849Abstract Full Text Full Text PDF PubMed Scopus (82) Google Scholar recently reported a 9.3 fold increased risk of developing lung cancer in heart and/or lung transplant recipients compared with the general population. When skin cancer was excluded, lung cancer was the third most common malignancy in these patients, following lymphoproliferative disorders and head and neck cancer. In this issue of the journal, Minai et al.4Minai OH Shah S Mazzone P et al.Bronchogenic carcinoma after lung transplantation: characteristics and outcomes.J Thoracic Oncol. 2008; 3: 1404-1409Abstract Full Text Full Text PDF PubMed Scopus (43) Google Scholar report the largest single center series of patients who developed bronchogenic carcinoma after lung transplantation. Their findings were not dissimilar from previous literature. In a cohort of 520 patients, 12 (2.3%) patients, all of whom were former smokers, developed 13 bronchogenic carcinomas. Most were of non-small cell histology. Eleven of the 12 patients had COPD and 1 had pulmonary fibrosis. Eleven of the 12 patients developed bronchogenic carcinoma in their native lungs. The prevalence of bronchogenic carcinoma was higher at 3.84% in patients receiving single lung transplantation and even higher at 5.15% among COPD patients who received single lung transplantation. Most patients were not amenable to curative surgical resection resulting in very poor outcomes within a year of diagnosis. Further review of literature by the authors led to the identification of 47 other patients who were diagnosed with bronchogenic carcinoma after transplantation and revealed similar demographic findings and outcomes. This article and previous literature on this topic bring up two important questions. First, should single lung transplantation be abandoned in patients with COPD and possibly pulmonary fibrosis because of the significantly increased risk of bronchogenic carcinoma in these patients? Similar to data presented by Minai et al., other reports on bronchogenic carcinoma after lung transplantation revealed a much higher prevalence in single lung recipients. A study specifically designed to look at risk factors showed that primary lung cancer occurred in 6.9% of single-lung recipients versus in none of bilateral lung recipients.5Dickson RP Davis RD Rea JB Palmer SM High frequency of bronchogenic carcinoma after single-lung transplantation.J Heart Lung Transplant. 2006; 25: 1297-1301Abstract Full Text Full Text PDF PubMed Scopus (72) Google Scholar In multivariate analysis, single lung transplantation conferred a relative risk of 5.3 for the development of lung cancer. Given this much higher than expected incidence and risk of lung cancer following single lung transplantation, with its attendant poor prognosis, a question that naturally follows, but cannot be easily answered, is whether single lung transplantation should be abandoned in patients at risk for posttransplant lung cancer, particularly those with smoking exposure and COPD. This question certainly poses a significant ethical dilemma, in which the benefit of bilateral lung transplantation in decreasing the risk of lung cancer with potential improvement in long-term outcomes will have to be balanced against the benefits of single lung transplantation to patients with fatal lung disease, allowing maximal resource utilization and prolongation of the lives of twice as many patients. The second question is the role of radiologic screening at regular intervals for candidates and recipients of lung transplantation. Screening by plain chest radiography is clearly inadequate in this patient population whose cancers are missed on prior radiographs approximately 50% of the time.6Collins J Kazerooni EA Lacomis J et al.Bronchogenic carcinoma after lung transplantation: frequency, clinical characteristics, and imaging findings.Radiology. 2002; 224: 131-138Crossref PubMed Scopus (59) Google Scholar Chest computed tomography (CT) represents a more sensitive, albeit imperfect detection tool with less than 15% chance of missing lesions. CT screening for lung cancer in other populations at risk remains controversial and is currently not recommended.7Bach PB Silvestri GA Hanger M Jett JR Screening for lung cancer: ACCP evidence-based clinical practice guidelines (2nd edition).Chest. 2007; 132: 69S-77SCrossref PubMed Scopus (130) Google Scholar In patients with advanced lung disease being considered for lung transplantation and who are at higher risk for lung cancer (former smokers with COPD and pulmonary fibrosis), it is unlikely that survival due to lung cancer detection will be altered by the screening process, particularly since most patients will not be amenable to curative resection. However, since lung transplantation is an incredibly expensive treatment modality available for only a small subset of patients, and the fact that transplantation of patients with preexisting lung cancer universally results in very poor outcomes, adding to the cost of pretransplant testing the expense of annual chest CT may be a small price to pay. With such a strategy, patients with malignancy can be excluded from transplantation, avoiding both the high cost and poor outcomes in this group of patients, and also allowing other patients to undergo transplantation. Posttransplant screening is perhaps more controversial, sparking the question whether outcomes of lung cancer can be improved by early detection in the immunosuppressed host. As a screening tool, the cost effectiveness of chest CT is certainly a major consideration, but less so in transplant patients who have already been committed to a very expensive treatment modality. In summary, bronchogenic cancer has become a significantly frequent and fatal complication in lung transplant recipients, predominantly affecting former smokers with COPD and pulmonary fibrosis who receive single lung transplantation. Our challenges are to resolve how best to detect lung cancer before and after lung transplantation, determine the most appropriate transplant procedure for patients at highest risk and understand the mechanisms by which lung cancer develops during chronic immunosuppressive therapy. All of these challenges, if overcome, may lead to a significant decrease in lung cancer-related mortality in transplant recipients." @default.
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• W2034290274 title "Controversies in Bronchogenic Carcinoma Following Lung Transplantation: Type of Transplant Operation and Role of Screening" @default.
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