Stanley B. Pearson

Genetic alterations in bronchial mucosa and plasma DNA from individuals at high risk of lung cancer

Evidence suggests that the majority of lung cancer patients have tumour‐derived genetic alterations in circulating plasma DNA, and that this may be developed as a diagnostic tool. To this end, we have studied 60 individuals attending bronchoscopy clinic, with symptoms suspicious of lung cancer, for genetic alterations in bronchial mucosa biopsy (n = 47) and plasma (n = 40) DNA. Thirteen of 47 individuals from whom biopsies were taken displayed allelic loss of heterozygosity (LOH) in biopsy DNA for at least 1 of 4 markers. All 13 of these individuals had neoplastic tumour cells in their biopsies and were subsequently diagnosed with cancer. Thirteen of 40 individuals from whom plasma was taken displayed a plasma DNA LOH, and 12 of these 13 individuals were subsequently diagnosed with cancer. LOH in plasma was generally representative of LOH in the corresponding biopsy. In terms of sensitivity, using just 4 markers, biopsy LOH and plasma LOH were found in 13 of 44 (30%) and 12 of 29 (41%), respectively, of those patients subsequently diagnosed with cancer. Two patients were positive for LOH in plasma samples that pre‐dated a diagnosis of cancer by several months. These data suggest that assay of genetic alterations in circulating plasma DNA may be developed as a useful addition to conventional techniques for the diagnosis of lung cancer.

Recurrent lung shadowing in adult juvenile idiopathic arthritis

A 25 year old Asian woman with a 11 year history of juvenile idiopathic arthritis (polyarthritis, rheumatoid factor positive) was referred from a peripheral hospital with poor disease control despite multiple disease modifying anti-rheumatic drugs (DMARDS). She was not a cigarette smoker and had been taking azathioprine 125 mg daily and prednisolone 5 mg daily for the past 10 months. Her past medical history included pulmonary tuberculosis diagnosed 14 months ago for which she had completed six months of antituberculous treatment. Details of her previous respiratory management including radiographs were not available. Physical examination revealed generalised synovitis with normal respiratory findings. She was treated with intra-articular corticosteroid injections into multiple joints and sulfasalazine was added to her above medications. Sulfasalazine was increased to a dose of 2 g daily over a four week period. One month later, she re-presented with about two weeks history of dry cough and dyspnoea. Physical examination revealed that she was apyrexial with normal respiratory findings and persistent synovitis. Based on her chest radiograph (fig 1A) showing patchy consolidation in the right lung, more prominently in the right mid and upper zones, and left lower zone, the presumed diagnosis was pneumonia, possibly with an atypical microorganism and she was treated with a course of ampicillin and erythromycin while investigations were performed. The main differential diagnosis was the recurrence of pulmonary tuberculosis. Laboratory investigations were largely unchanged from the previous month, with a normochromic …