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Lung transplantation: a treatment option in end-stage lung disease.

Dtsch Arztebl Int. 2014 Feb 14;111(7):107-16

Authors: Hartert M, Senbaklavacin O, Gohrbandt B, Fischer BM, Buhl R, Vahld CF

Abstract
BACKGROUND: Lung transplantation is the final treatment option in the end stage of certain lung diseases, once all possible conservative treatments have been exhausted. Depending on the indication for which lung transplantation is performed, it can improve the patient's quality of life (e.g., in emphysema) and/ or prolong life expectancy (e.g., in cystic fibrosis, pulmonary fibrosis, and pulmonary arterial hypertension). The main selection criteria for transplant candidates, aside from the underlying pulmonary or cardiopulmonary disease, are age, degree of mobility, nutritional and muscular condition, and concurrent extrapulmonary disease. The pool of willing organ donors is shrinking, and every sixth candidate for lung transplantation now dies while on the waiting list.
METHOD: We reviewed pertinent articles (up to October 2013) retrieved by a selective search in Medline and other German and international databases, including those of the International Society for Heart and Lung Transplantation (ISHLT), Eurotransplant, the German Institute for Applied Quality Promotion and Research in Health-Care (Institut für angewandte Qualitätsförderung und Forschung im Gesundheitswesen, AQUA-Institut), and the German Foundation for Organ Transplantation (Deutsche Stiftung Organtransplantation, DSO).
RESULTS: The short- and long-term results have markedly improved in recent years: the 1-year survival rate has risen from 70.9% to 82.9%, and the 5-year survival rate from 46.9% to 59.6%. The 90-day mortality is 10.0%. The postoperative complications include acute (3.4%) and chronic (29.0%) transplant rejection, infections (38.0%), transplant failure (24.7%), airway complications (15.0%), malignant tumors (15.0%), cardiovascular events (10.9%), and other secondary extrapulmonary diseases (29.8%). Bilateral lung transplantation is superior to unilateral transplantation (5-year survival rate 57.3% versus 47.4%).
CONCLUSION: Seamless integration of the various components of treatment will be essential for further improvements in outcome. In particular, the follow-up care of transplant recipients should always be provided in close cooperation with the transplant center.

PMID: 24622680 [PubMed - in process]

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OBJECTIVES: Surgical lung biopsy (SLB) by videothoracoscopy for diffuse interstitial lung diseases is recommended for detailed diagnosis. Because substantial mortality and morbidity are associated with this procedure, its safety and diagnostic yield should be validated.

METHODS: Sixty-four patients with diffuse interstitial lung disease who received SLB by videothoracoscopy between 2007 and 2013 were retrospectively analyzed for mortality, surgical complication, and diagnosis. Criteria for the procedure included patients <70-year old, who had at least 60 % vital capacity and at least 40 % diffusion capacity. Patients with radiologically definite usual interstitial pneumonia were not eligible.

RESULTS: One conversion from the 3-port approach to thoracotomy due to bleeding occurred. Mean operation and anesthesia times were 63 and 133 min, respectively. The mean hospital stay was 6 days. Only 10 patients (16 %) received prophylactic steroid and/or elastase inhibitor administration. Neither deaths nor acute exacerbations of interstitial pneumonia occurred within 60 days after surgery. Pneumothorax occurred in four cases (6 %) after discharge, which was associated with lower % vital capacity and intraoperative steroid administration. Prolonged air leak and postoperative pneumonia were observed in 2 and 1 patients, respectively. Postoperative diagnosis was obtained in all patients. A group of connective tissue disease-related interstitial pneumonia (n = 15) and chronic hypersensitivity pneumonitis (n = 18) were the major diagnoses. Discordance between pre- and postoperative diagnoses was observed among usual interstitial pneumonia, non-specific interstitial pneumonia, and chronic hypersensitivity pneumonia.

CONCLUSIONS: Surgical lung biopsy for diffuse interstitial lung diseases is safe under appropriate inclusion criteria and provides definite diagnosis.

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Today, molecular-profile-directed therapy is a guiding principle of modern thoracic oncology. The knowledge of new biomolecular technology applied to the diagnosis, prognosis, and treatment of lung cancer and mesothelioma should be part of the 21st century thoracic surgeons' professional competence.

The European Society of Thoracic Surgeons (ESTS) Biology Club aims at providing a comprehensive insight into the basic biology of the diseases we are treating. During the 2013 ESTS Annual Meeting, different experts of the field presented the current knowledge about diagnostic and prognostic biomarkers in malignant pleural mesothelioma including new perspectives as well as the role and potential application of microRNA and genomic sequencing for lung cancer, which are summarized in the present article.

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The fusion of echinoderm microtubule-associated protein-like 4 with anaplastic lymphoma kinase (ALK) was identified as a transforming gene for lung cancer in 2007. This genetic rearrangement accounts for 2%-5% of non-small-cell lung cancer (NSCLC) cases, occurring predominantly in younger individuals with adenocarcinoma who are never- or light smokers.

A small-molecule tyrosine-kinase inhibitor of ALK, crizotinib, was rapidly approved by the US Food and Drug Administration on the basis of its pronounced clinical activity in patients with ALK rearrangement-positive NSCLC. Next-generation ALK inhibitors, such as alectinib, LDK378, and AP26113, are also being developed in ongoing clinical trials. In addition, the improvement and validation of methods for the detection of ALK rearrangement in NSCLC patients will be key to the optimal clinical use of ALK inhibitors.

We here summarize recent progress in the development of new ALK inhibitors and in the molecular diagnosis of ALK rearrangement-positive NSCLC.

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