Genome sequencing reveals underdiagnosis of primary ciliary dyskinesia in bronchiectasis.

BACKGROUND: Bronchiectasis can result from infectious, genetic, immunological and allergic causes. 60-80% of cases are idiopathic, but a well-recognised genetic cause is the motile ciliopathy, primary ciliary dyskinesia (PCD). Diagnosis of PCD has management implications including addressing comorbidities, implementing genetic and fertility counselling and future access to PCD-specific treatments. Diagnostic testing can be complex; however, PCD genetic testing is moving rapidly from research into clinical diagnostics and would confirm the cause of bronchiectasis. METHODS: This observational study used genetic data from severe bronchiectasis patients recruited to the UK 100,000 Genomes Project and patients referred for gene panel testing within a tertiary respiratory hospital. Patients referred for genetic testing due to clinical suspicion of PCD were excluded from both analyses. Data were accessed from the British Thoracic Society audit, to investigate whether motile ciliopathies are underdiagnosed in people with bronchiectasis in the UK. RESULTS: Pathogenic or likely pathogenic variants were identified in motile ciliopathy genes in 17 (12%) out of 142 individuals by whole-genome sequencing. Similarly, in a single centre with access to pathological diagnostic facilities, 5-10% of patients received a PCD diagnosis by gene panel, often linked to normal/inconclusive nasal nitric oxide and cilia functional test results. In 4898 audited patients with bronchiectasis, <2% were tested for PCD and <1% received genetic testing. CONCLUSIONS: PCD is underdiagnosed as a cause of bronchiectasis. Increased uptake of genetic testing may help to identify bronchiectasis due to motile ciliopathies and ensure appropriate management.

Long-term follow-up of testicular cancer patients shows no predisposition to osteoporosis.

UNLABELLED: Most patients with testis cancer are cured with treatment. However, the incidence of osteoporosis after prolonged follow-up is unknown. This study investigates the incidence of osteoporosis in 39 testis cancer patients with follow-up from 5 to 28 years. There was no increased incidence of osteoporosis. These initial data are reassuring but require further investigation. INTRODUCTION: The majority of patients with testis cancer are cured with either a unilateral orchidectomy alone or orchidectomy and chemotherapy. However, the long-term incidence of osteoporosis following treatment for testicular cancer has not been established. METHOD: This was a single-centre cross-sectional study, where bone mineral density (BMD) measurements were performed in male patients who were previously treated for testicular cancer. BMD measurements were made by dual-energy X-ray scanning (DXA) using a HOLOGIC imaging bone densitometer. The World Health Organisation criteria were used to define osteoporosis and osteopenia. Blood samples were taken from each patient at the time of the DXA scan. Statistical analyses were performed in STATA10. RESULTS: Neither orchidectomy alone nor orchidectomy and chemotherapy together predisposed to osteoporosis [p value = 0.4 (95%CI -0.1-0.8) and p value = 0.2 (95%CI -0.2-0.7), respectively]. Analysis also showed no evidence of an association between cases of osteopenia and length of follow-up (assessed by logistic regression). CONCLUSION: This work found no association between treatment for testis cancer and the development of osteoporosis. Screening the whole population of testis cancer survivors for osteoporosis in the long term is not necessary; however, targeting specific patients with risk factors may be warranted.

A review of the close surveillance policy for stage I female germ cell tumors of the ovary and other sites.

Ovarian germ cell tumors are rare but very curable at all stages of disease. There is good evidence that surveillance for stage I dysgerminomas is a safe option although many centers worldwide still advocate adjuvant chemotherapy for stage IA nondysgerminomatous tumors, despite the significant risk of developing long-term treatment side effects. Here, we review the safety of our ongoing surveillance program of all stage IA female germ cell tumors. Thirty-seven patients (median age 26, range 14-48 years) with stage I disease were referred to Mount Vernon and Charing Cross Hospitals between 1981 and 2003. Patients underwent surgery and staging followed by intense surveillance, which included regular tumor markers and imaging. The median period of follow-up was 6 years. Relapse rates for stage IA nondysgerminomatous tumors and dysgerminomas were 8 of 22 (36%) and 2 of 9 (22%), respectively, plus one patient with mature teratoma and glial implants also relapsed; 10 of these 11 patients (91%) were successfully cured with platinum-based chemotherapy. Only one patient died from chemoresistant disease. All relapses occurred within 13 months of initial surgery. The overall disease-specific survival of malignant ovarian germ cell tumors was 94%. Over 50% of patients who underwent fertility-sparing surgery went on to have successful pregnancies. We have confirmed again that surveillance of all stage IA ovarian germ cell tumors is very safe and that the outcome is comparable with testicular tumors. We question the need for potentially toxic adjuvant chemotherapy in nondysgerminoma patients who have greater than 90% chance of being salvaged with chemotherapy if they relapse later.