Prevalence, molecular markers, and outcome of bronchial squamous carcinoma in situ in high-risk subjects

Publisher Copyright: © 2023 The Authors. APMIS published by John Wiley & Sons Ltd on behalf of Scandinavian Societies for Pathology, Medical Microbiology and Immunology. © 2023 The Authors. APMIS published by John Wiley & Sons Ltd on behalf of Scandinavian Societies for Pathology, Medical Microbiology and Immunology.Bronchial squamous carcinoma in situ (CIS) is a preinvasive lesion that is thought to precede invasive carcinoma. We conducted prospective autofluorescence and white light bronchoscopy trials between 1992 and 2016 to assess the prevalence, molecular markers, and outcome of individuals with CIS and other preneoplastic bronchial lesions. Biopsies were evaluated at multiple levels and selected biopsies were tested for aneuploidy and DNA sequenced for TP53 mutation. Thirty-one individuals with CIS were identified. Twenty-two cases of CIS occurred in association with concurrent invasive carcinomas. Seven of the invasive tumors were radiographically occult. In two cases, CIS spread from the focus of invasive carcinoma into contralateral lung lobes, forming secondary invasive tumors. In nine cases, CIS occurred as isolated lesions and one progressed to invasive squamous carcinoma at the same site 40 months after discovery. In a second case, CIS was a precursor of carcinoma at a separate site in a different lobe. In seven cases CIS regressed to a lower grade or disappeared. High level chromosomal aneusomy was often associated with TP53 mutation and with invasive carcinoma. CIS most often occurs in association with invasive squamous carcinoma and may extend along the airways into distant lobes. In rare cases, CIS may be observed to directly transform into invasive carcinoma. CIS may be indicative of invasive tumor at a separate distant site. Isolated CIS may regress. Molecular changes parallel histological changes in CIS and may be used to map clonal expansion in the airways.Peer reviewe

Pneumococcal vaccination: Direct and herd effect on carriage of vaccine types and antibiotic resistance in Icelandic children

Background Since the introduction of pneumococcal conjugate vaccines, vaccine type pneumococcal carriage and disease has decreased world-wide. The aim was to monitor changes in the nasopharyngeal carriage of pneumococci, the distribution of serotypes and antimicrobial resistance in children before and after initiation of the 10-valent pneumococcal vaccination in 2011, in a previously unvaccinated population. Methods Repeated cross-sectional study at 15 day-care centres in greater Reykjavik area. Nasopharyngeal swabs were collected yearly in March from 2009 to 2015. The swabs were selectively cultured for pneumococci, which were serotyped using latex agglutination and/or PCR and antimicrobial susceptibility determined. Two independent studies were conducted. In study 1, on total impact, isolates from children aged <4 years were included. The vaccine-eligible-cohort (birth-years: 2011–2013, sampled in 2013–2015) was compared with children at the same age born in 2005–2010 and sampled in 2009–2012. In study 2 on herd effect, isolates from older non-vaccine-eligible children (3.5–6.3 years) were compared for the periods before and after the vaccination (2009–2011 vs 2013–2015. Vaccine impact was determined using 1-odds-ratio. Results Following vaccination, the vaccine impact on vaccine type acquisition was 94% (95% CI: 91–96%) in study 1 and 56% (95% CI: 44–65%) in study 2. The impact on serotype 6 A was 33% (95% CI: −9%; 59%) in study 1 and 42% (95% CI: 10–63%) in study 2 with minimal effect on 19A. The non-vaccine serotypes/groups 6C, 11, 15 and 23B were the most common serotypes/groups after vaccination. Isolates from the vaccine-eligible-cohort had lower penicillin MICs, less resistance to erythromycin and co-trimoxazole and less multi resistance than isolates from the control-group. Conclusions The efficacy of the vaccination on vaccine serotypes was high, and a milder effect on vaccine-associated-serotype 6A was observed for the vaccine-eligible-cohort. There was a significant herd effect on vaccine types in older non-vaccine-eligible children. Overall antimicrobial non-susceptibility was reduced.Funding for this study was provided by GlaxoSmithKline Biologicals SA and a grant was received from the Landspitali University Hospital Research Fund. GlaxoSmithKline Biologicals SA was provided the opportunity to review a draft version of this manuscript but the authors are solely responsible for final content and interpretation. The authors received no financial support or other form of compensation related to the development of the manuscript.Peer Reviewe