Contemporary review of the organ care system in lung transplantation: potential advantages of a portable ex-vivo lung perfusion system.

Expert Rev Med Devices. 2016 Oct 11;

Authors: Schmack B, Weymann A, Mohite P, Garcia Saez D, Zych B, Sabashnikov A, Zeriouh M, Schamroth J, Koch A, Soresi S, Ananiadou O, De Robertis F, Karck M, Simon AR, Popov AF

Abstract
INTRODUCTION: Lung transplantation remains the definite treatment for various end-stage lung diseases. Cold flush perfusion, the standard method for organ procurement has severe limitations. Organ Care System (OCS; TransMedics, Inc., Andover, USA) is an approved method to preserve hearts for transplantation that allows for greatly reduced cold ischemic time. Consequently, the use of an adapted OCS lung as a portable full ex-vivo lung perfusion system in lung transplantation is currently under close evaluation. Areas covered: The aim of this article is to review the advantages and the role of the OCS in the field of lung transplantation by reviewing the latest literature and evaluating this novel procurement technique in the context of conventional methods like cold flush and regular ex-vivo lung perfusion. Expert Commentary: The use of OCS in the field of lung transplantation has great potential for improved patients outcomes and is justified in cases with (i) marginal donor lungs, (ii) foreseeable long time of transportation (iii) high-risk recipient or donor /recipient profiles, particularly in the setting of an overall increasing need for suitable donor organs. Results from two major multi-centre prospective studies are pending to objectively assess the possible advantages of this portable ex-vivo lung perfusion system.

PMID: 27728991 [PubMed - as supplied by publisher]

Dendritic cells in human lung disease: recent advances.

Chest. 2016 Oct 8;:

Authors: Upham JW, Xi Y

Abstract
Dendritic cells (DC) are potent antigen presenting cells. Because of their particular ability to initiate and regulate cell mediated and humoral immune responses, there is considerable interest in the role that DC play in the pathogenesis of various lung diseases, especially those in which there is an excessive immune response to specific antigens (as in asthma) or a deficient immune response (as in lung cancer). A number of DC subpopulations have been defined in the lungs including myeloid or conventional DC that initiate T-cell immunity and antibody production, and plasmacytoid DC that have an important role in anti-viral immunity and immune tolerance. Though an extensive body of literature has documented the role that DC play in experimental models of lung disease, this review will highlight recent advances in our understanding of DC function in human disease, including asthma, COPD, anti-microbial immunity and lung cancer. The future is likely to see new approaches whereby antigens and small molecules are targeted to receptors on particular DC subpopulations in order to modify pulmonary immune responses.

PMID: 27729261 [PubMed - as supplied by publisher]

BACKGROUND: Surgical lung biopsy (SLB) is invasive and not possible in all patients with undiagnosed interstitial lung diseases (ILD). We hypothesized that transbronchial biopsy (TBB) findings combined with clinical and high resolution computed tomography (HRCT) data leads to a confident diagnosis congruent to SLB, and therefore avoids the need for SLB in some patients.

METHODS: We evaluated 33 patients being evaluated for suspected ILD who underwent HRCT, TBB and SLB. First, clinicians, radiologists and a pathologist reviewed the clinical information, HRCT and TBB. Clinicians were asked to provide a diagnosis, and if SLB was needed for more confident diagnosis. Subsequently, the clinical, HRCT and SLB data were reviewed, and the same participants were asked to provide a final diagnosis. Clinician consensus and overall agreement between TBB and SLB based diagnoses were calculated.

RESULTS: Four patients had definite UIP on HRCT and would not be considered for biopsy using current guidelines. Of the 29 patients without a definitive HRCT diagnosis, the clinicians felt confident of the diagnosis (i.e. would not recommend SLB) in 6 cases. In these cases there was 100% agreement between TBB and SLB diagnoses. Usual interstitial pneumonia was the most common diagnosis (n=3) and was associated with an HRCT diagnosis of possible UIP/NSIP-like. Agreement was poor (33%) between TBB and SLB diagnosis when confidence in TBB diagnosis was low.

CONCLUSIONS: Information from TBB, when combined with clinical and HRCT data, may provide enough information to make a confident and accurate diagnosis in approximately 20-30% of patients with ILD.

Over the past few years, there have been considerable advances in the treatments available to patients with metastatic or locally advanced non-small cell lung cancer (NSCLC), particularly those who have progressed on or during first-line treatment. Some of the treatment options available to patients are discussed here, with a focus on checkpoint inhibitor immunotherapies (nivolumab and pembrolizumab) and antiangiogenic agents (bevacizumab, ramucirumab and nintedanib). It is hypothesised that combining immunotherapy with antiangiogenic treatment may have a synergistic effect and enhance the efficacy of both treatments.

In this review, we explore the theory and potential of this novel treatment option for patients with advanced NSCLC. We discuss the growing body of evidence that pro-angiogenic factors can modulate the immune response (both by reducing T-cell infiltration into the tumour microenvironment, and through systemic effects on immune-regulatory cell function) and examine the preclinical evidence for combining these treatments. Potential challenges are also considered, and we review the preliminary evidence of clinical efficacy and safety with this novel combination in a variety of solid tumour types.