Focal 18 F-FDG uptake predicts progression of pre-invasive squamous bronchial lesions to invasive cancers.

INTRODUCTION: Pre-invasive squamous lesions of the central airways can progress into invasive lung cancers. Identifying these high-risk patients could enable detection of invasive lung cancers at an early stage. In this study, we investigated the value of 18 F-fluorodeoxyglucose (18 F-FDG) positron emission tomography (PET) scans in predicting progression in patients with pre-invasive squamous endobronchial lesions. METHODS: In this retrospective study, patients with pre-invasive endobronchial lesions, who underwent an 18 F-FDG PET scan at the VU University Medical Center Amsterdam, between January 2000 and December 2016, were included. Autofluorescence bronchoscopy (AFB) was used for tissue sampling and was repeated every 3 months. The minimum and median follow-up was 3 and 46.5 months. Study endpoints were the occurrence of biopsy proven invasive carcinoma, time-to-progression and overall survival (OS). RESULTS: A total number of 40 of 225 patients met the inclusion criteria of which 17 (42.5%) patients had a positive baseline 18 F-FDG PET scan. A total of 13 of 17 (76.5%) developed invasive lung carcinoma during follow-up, with a median time to progression of 5.0 months (range, 3.0-25.0). In 23 (57.5%) patients with a negative 18 F-FDG PET scan at baseline, 6 (26%) developed lung cancer, with a median time to progression of 34.0 months (range, 14.0-42.0 months, p < 0.002). With a median OS of 56.0 months (range, 9.0-60.0 months) versus 49.0 months (range, 6.0-60.0 months) (p = 0.876) for the 18 F-FDG PET positive and negative groups, respectively. CONCLUSIONS: Patients with pre-invasive endobronchial squamous lesions and a positive baseline 18 F-FDG PET scan were at high-risk for developing lung carcinoma, highlighting that this patient group requires early radical treatment.

Diagnostic yield of a targeted gene panel in primary ciliary dyskinesia patients.

We aimed to determine the diagnostic yield of a targeted-exome panel in a cohort of 74 Dutch primary ciliary dyskinesia (PCD) patients. The panel consisted of 26 PCD-related and 284 candidate genes. To prioritize PCD candidate genes, we investigated the transcriptome of human airway cells of 12 healthy volunteers during in vitro ciliogenesis and hypothesized that PCD-related genes show significant upregulation. We compared gene expression in epithelial precursor cells grown as collagen monolayer and ciliated cells grown in suspension by RNA sequencing. All genes reported as PCD causative, except NME8, showed significant upregulation during in vitro ciliogenesis. We observed 67.6% diagnostic yield when testing the targeted-exome panel in our cohort. There was relatively high percentage of DNAI and HYDIN mutations compared to other countries. The latter may be due to our solution for the problem of the confounding HYDIN2 pseudogene. Candidate genes included two recently published PCD-related genes DNAJB13 and PIH1D3; identification of the latter was a direct result of this study. In conclusion, we demonstrate 67.6% diagnostic yield by targeted exome sequencing in a Dutch PCD population and present a highly sensitive and moderately specific approach for identification of PCD-related genes, based on significant upregulation during in vitro ciliogenesis.