Immune Surveillance in Clinical Regression of Preinvasive Squamous Cell Lung Cancer.

Before squamous cell lung cancer develops, precancerous lesions can be found in the airways. From longitudinal monitoring, we know that only half of such lesions become cancer, whereas a third spontaneously regress. Although recent studies have described the presence of an active immune response in high-grade lesions, the mechanisms underpinning clinical regression of precancerous lesions remain unknown.

Sequential screening for lung cancer in a high-risk group: randomised controlled trial: LungSEARCH: a randomised controlled trial of Surveillance using sputum and imaging for the EARly detection of lung Cancer in a High-risk group.

Background: Low-dose computed tomography (LDCT) screening detects early-stage lung cancer and reduces mortality. We proposed a sequential approach targeted to a high-risk group as a potentially efficient screening strategy.

Methods: LungSEARCH was a national multicentre randomised trial.

The surgical management of non-malignant aerodigestive fistula.

Background: Acquired aerodigestive fistula (ADF) are rare, but associated with significant morbidity. Surgery affords the best prospect of cure. We present our experience of the surgical management of ADFs at a specialist unit, highlighting operative techniques, challenges and assess clinical outcomes following intervention.

Acquired Adult Aerodigestive Fistula: Classification and Management.

Background: Acquired aerodigestive fistulae (ADF) are rare, but associated with a high mortality rate. We present our experience of the diagnosis, management and outcomes of patients with ADFs treated at a tertiary centre. Utilising our findings, we propose an anatomical classification system, demonstrating how specific features of an ADF may determine management.

CADM1 inhibits squamous cell carcinoma progression by reducing STAT3 activity.

Although squamous cell carcinomas (SqCCs) of the lungs, head and neck, oesophagus, and cervix account for up to 30% of cancer deaths, the mechanisms that regulate disease progression remain incompletely understood. Here, we use gene transduction and human tumor xenograft assays to establish that the tumour suppressor Cell adhesion molecule 1 (CADM1) inhibits SqCC proliferation and invasion, processes fundamental to disease progression. We determine that the extracellular domain of CADM1 mediates these effects by forming a complex with HER2 and integrin α6β4 at the cell surface that disrupts downstream STAT3 activity.

Interventional bronchoscopy in the management of thoracic malignancy.

Interventional bronchoscopy is a rapidly expanding field in respiratory medicine offering minimally invasive therapeutic and palliative procedures for all types of lung neoplasms. This field has progressed over the last couple of decades with the application of new technology. The HERMES European curriculum recommendations include interventional bronchoscopy skills in the modules of thoracic tumours and bronchoscopy [1].

Not always asthma: clinical and legal consequences of delayed diagnosis of laryngotracheal stenosis.

Laryngotracheal stenosis (LTS) is a rare condition that occurs most commonly as a result of instrumentation of the airway but may also occur as a result of inflammatory conditions or idiopathically. Here, we present the case of a patient who developed LTS as a complication of granulomatosis with polyangiitis (GPA), which was misdiagnosed as asthma for 6 years. After an admission with respiratory symptoms that worsened to the extent that she required intubation, a previously well 14-year-old girl was diagnosed with GPA.

Cell migration leads to spatially distinct but clonally related airway cancer precursors.

Background: Squamous cell carcinoma of the lung is a common cancer with 95% mortality at 5 years. These cancers arise from preinvasive lesions, which have a natural history of development progressing through increasing severity of dysplasia to carcinoma in situ (CIS), and in some cases, ending in transformation to invasive carcinoma. Synchronous preinvasive lesions identified at autopsy have been previously shown to be clonally related.

Management and prognosis of primary tracheal cancer: a national analysis.

Objectives/hypothesis: To perform a national review of the incidence and treatment of primary tracheal cancer and to identify gaps in service provision and factors associated with survival.

Study Design: Retrospective analysis of Hospital Episode Statistics data for England between 1996 and 2011.

Methods: Information about age, sex, morbidity, provider trust, diagnostic delay, nature of hospital admission and treatment, and palliation-free survival were recorded.

Diagnosis of laryngotracheal stenosis from routine pulmonary physiology using the expiratory disproportion index.

Objective/hypothesis: The study's objective was to determine the utility of expiratory disproportion index (EDI), the ratio of forced expiratory volume in 1 second (FEV1) to peak expiratory flow rate (PEFR) (EDI = FEV1[L] /PEFR[L/s] × 100), in differentiating between laryngotracheal stenosis (LTS) and other respiratory diagnoses. LTS is an uncommon complication of mechanical ventilation or vasculitis or a manifestation of airway compression or malignancy. It frequently masquerades as asthma and evades timely diagnosis, causing prolonged morbidity and airway-related mortality.

LRIG1 regulates cadherin-dependent contact inhibition directing epithelial homeostasis and pre-invasive squamous cell carcinoma development.

Epidermal growth factor receptor (EGFR) pathway activation is a frequent event in human carcinomas. Mutations in EGFR itself are, however, rare, and the mechanisms regulating EGFR activation remain elusive. Leucine-rich immunoglobulin repeats-1 (LRIG1), an inhibitor of EGFR activity, is one of four genes identified that predict patient survival across solid tumour types including breast, lung, melanoma, glioma, and bladder.

β-Catenin determines upper airway progenitor cell fate and preinvasive squamous lung cancer progression by modulating epithelial-mesenchymal transition.

Human lung cancers, including squamous cell carcinoma (SCC) are a leading cause of death and, whilst evidence suggests that basal stem cells drive SCC initiation and progression, the mechanisms regulating these processes remain unknown. In this study we show that β-catenin signalling regulates basal progenitor cell fate and subsequent SCC progression. In a cohort of preinvasive SCCs we established that elevated basal cell β-catenin signalling is positively associated with increased disease severity, epithelial proliferation and reduced intercellular adhesiveness.

Outcome of treating airway compromise due to bronchial stenosis with intralesional corticosteroids and cutting-balloon bronchoplasty.

Objectives: To determine the feasibility, safety, and efficacy of treating benign bronchial stenosis with laryngoscopy, jet ventilation, intralesional corticosteroids, and cutting-balloon bronchoplasty.

Study Design: Case series with planned data collection.

Setting: National airway unit.

Genomic evidence of pre-invasive clonal expansion, dispersal and progression in bronchial dysplasia.

The term 'field cancerization' is used to describe an epithelial surface that has a propensity to develop cancerous lesions, and in the case of the aerodigestive tract this is often as a result of chronic exposure to carcinogens in cigarette smoke 1, 2. The clinical endpoint is the development of multiple tumours, either simultaneously or sequentially in the same epithelial surface. The mechanisms underlying this process remain unclear; one possible explanation is that the epithelium is colonized by a clonal population of cells that are at increased risk of progression to cancer.

Progressive 3q amplification consistently targets SOX2 in preinvasive squamous lung cancer.

Rationale: Amplification of distal 3q is the most common genomic aberration in squamous lung cancer (SQC). SQC develops in a multistage progression from normal bronchial epithelium through dysplasia to invasive disease. Identifying the key driver events in the early pathogenesis of SQC will facilitate the search for predictive molecular biomarkers and the identification of novel molecular targets for chemoprevention and therapeutic strategies.

Central airway obstruction caused by a peripheral hamartoma.

We report the first case of a hamartoma, arising from peripheral lung tissue, which extended proximally over several decades to occlude the large airways. The patient's symptoms were originally attributed to asthma and the correct diagnosis was only made when she developed life-threatening airway obstruction. The endobronchial component of the hamartoma was debulked with urgent laser therapy, while the peripheral base of the tumour was resected by elective right middle lobectomy.

Early lung cancer: screening and detection.

The most significant factor which determines the survival of a patient newly-diagnosed with lung cancer is the stage at which the disease has been diagnosed. Late diagnosis is common. This review focuses upon the possibility of earlier diagnosis using various cytological and radiological imaging techniques such as sputum cytology or cytometry, CT scanning, and fluorescence bronchoscopy.

Surveillance for the detection of early lung cancer in patients with bronchial dysplasia.

Background: The natural history of bronchial preinvasive lesions and the risk of developing lung cancer in patients with these lesions are not clear. Previous studies have treated severe dysplasia and carcinoma in situ (CIS) on the assumption that most will progress to invasive carcinoma.

Aims: To define the natural history of preinvasive lesions and assess lung cancer risk in patients with these lesions.

Somatic genetic changes accompanying lung tumor development.

Carcinomas are believed to develop by incremental steps of increasingly abnormal morphology driven by accumulating somatic genetic changes. This process is often difficult to study, as the early stages are undetectable. We used fluorescence bronchoscopy, which enhances detection of preinvasive bronchial lesions, and have obtained sequential biopsies of carcinoma in situ (CIS) from a patient with no detectable tumor and from a squamous cell carcinoma that developed 19 months after presentation at the site of one of the previous CIS lesions.

Survival benefits of lung cancer patients undergoing laser and brachytherapy.

We aimed to compare the duration of survival among subjects receiving brachytherapy (BT) in combination with Nd:YAG laser therapy (LT), and those receiving LT or BT alone. The medical records of subjects who received endobronchial treatment for unresectable tracheobronchial malignancies between January 1997 and December 1999 in a single center were reviewed retrospectively. A total of 80 patients were evaluated.