Tumor Cavitation in Patients With Stage III Non-Small-Cell Lung Cancer Undergoing Concurrent Chemoradiotherapy: Incidence and Outcomes.

J Thorac Oncol. 2012 May 31;

Authors: Phernambucq EC, Hartemink KJ, Smit EF, Paul MA, Postmus PE, Comans EF, Senan S

Abstract
INTRODUCTION:: Commonly reported complications after concurrent chemoradiotherapy (CCRT) in patients with stage III non-small-cell lung cancer (NSCLC) include febrile neutropenia, radiation esophagitis, and pneumonitis. We studied the incidence of tumor cavitation and/or "tumor abscess" after CCRT in a single-institutional cohort. METHODS:: Between 2003 and 2010, 87 patients with stage III NSCLC underwent cisplatin-based CCRT and all subsequent follow-up at the VU University Medical Center. Diagnostic and radiotherapy planning computed tomography scans were reviewed for tumor cavitation, which was defined as a nonbronchial air-containing cavity located within the primary tumor. Pulmonary toxicities scored as Common Toxicity Criteria v3.0 of grade III or more, occurring within 90 days after end of radiotherapy, were analyzed. RESULTS:: In the entire cohort, tumor cavitation was observed on computed tomography scans of 16 patients (18%). The histology in cavitated tumors was squamous cell (n = 14), large cell (n = 1), or adenocarcinoma (n = 1). Twenty patients (23%) experienced pulmonary toxicity of grade III or more, other than radiation pneumonitis. Eight patients with a tumor cavitation (seven squamous cell carcinoma) developed severe pulmonary complications; tumor abscess (n = 5), fatal hemorrhage (n = 2), and fatal embolism (n = 1). Two patients with a tumor abscess required open-window thoracostomy post-CCRT. The median overall survival for patients with or without tumor cavitation were 9.9 and 16.3 months, respectively (p = 0.09). CONCLUSIONS:: With CCRT, acute pulmonary toxicity of grade III or more developed in 50% of patients with stage III NSCLC, who also had radiological features of tumor cavitation. The optimal treatment of patients with this presentation is unclear given the high risk of a tumor abscess.

PMID: 22659960 [PubMed - as supplied by publisher]

Association of CFTR gene mutation with bronchial asthma.

Indian J Med Res. 2012 Apr;135(4):469-78

Authors: Maurya N, Awasthi S, Dixit P

Abstract
Mutation on both the copies of cystic fibrosis transmembrane conductance regulator (CFTR) gene results in cystic fibrosis (CF), which is a recessively transmitted genetic disorder. It is hypothesized that individuals heterozygous for CFTR gene mutation may develop obstructive pulmonary diseases like asthma. There is great heterogeneity in the phenotypic presentation and severity of CF lung disease. This could be due to genetic or environmental factors. Several modifier genes have been identified which may directly or indirectly interact with CFTR pathway and affect the severity of disease. This review article discusses the information related to the association of CFTR gene mutation with asthma. Association between CFTR gene mutation and asthma is still unclear. Report ranges from studies showing positive or protective association to those showing no association. Therefore, studies with sufficiently large sample size and detailed phenotype are required to define the potential contribution of CFTR in the pathogenesis of asthma.

PMID: 22664493 [PubMed - in process]

Cellular and humoral mechanisms involved in the control of tuberculosis.

Clin Dev Immunol. 2012;2012:193923

Authors: Zuñiga J, Torres-García D, Santos-Mendoza T, Rodriguez-Reyna TS, Granados J, Yunis EJ

Abstract
Mycobacterium tuberculosis (Mtb) infection is a major international public health problem. One-third of the world's population is thought to have latent tuberculosis, a condition where individuals are infected by the intracellular bacteria without active disease but are at risk for reactivation, if their immune system fails. Here, we discuss the role of nonspecific inflammatory responses mediated by cytokines and chemokines induced by interaction of innate receptors expressed in macrophages and dendritic cells (DCs). We also review current information regarding the importance of several cytokines including IL-17/IL-23 in the development of protective cellular and antibody-mediated protective responses against Mtb and their influence in containment of the infection. Finally, in this paper, emphasis is placed on the mechanisms of failure of Mtb control, including the immune dysregulation induced by the treatment with biological drugs in different autoimmune diseases. Further functional studies, focused on the mechanisms involved in the early host-Mtb interactions and the interplay between host innate and acquired immunity against Mtb, may be helpful to improve the understanding of protective responses in the lung and in the development of novel therapeutic and prophylactic tools in TB.

PMID: 22666281 [PubMed - in process]

Hypersensitivity Pneumonitis: Insights in Diagnosis and Pathobiology.

Am J Respir Crit Care Med. 2012 Jun 7;

Authors: Selman M, Pardo A, King TE

Abstract
Hypersensitivity pneumonitis (HP) is a complex syndrome resulting from repeated exposure to a variety of organic particles. HP may present as acute, subacute, or chronic clinical forms, but with frequent overlap of these various forms. An intriguing question is why only few of the exposed individuals develop the disease. According to a two-hit model, antigen exposure associated with genetic or environmental promoting factors provoke an immunopathological response. This response is mediated by immune complexes in the acute form and by Th1 and likely Th17 T-cells in subacute/chronic cases. Pathologically, HP is characterized by a bronchiolocentric granulomatous lymphocytic alveolitis, which evolves to fibrosis in chronic advanced cases. On high resolution computed tomography, ground-glass and poorly defined nodules, with patchy areas of air trapping, are seen in acute/subacute cases, while reticular opacities, volume loss and traction bronchiectasis superimposed on subacute changes are observed in chronic patients. Importantly, subacute and chronic HP may mimic several interstitial lung diseases including non-specific interstitial pneumonia and usual interstitial pneumonia making diagnosis extremely difficult. Thus, the diagnosis of HP requires a high index of suspicion and should be considered in any patient consulting with clinical evidence of ILD. The definitive diagnosis requires exposure to known antigen, and the assemblage of clinical, radiologic, laboratory, and pathologic findings. Early diagnosis and avoidance of further exposure are keys in management of the disease. Corticosteroids are generally used, although its long-term efficacy has not been proved in prospective clinical trials. Lung transplantation should be recommended in cases of progressive end-stage illness.

PMID: 22679012 [PubMed - as supplied by publisher]