Kousuke Tanimoto

Background The recurrence rate of non‐small cell lung cancer (NSCLC) is as high as 30%, even in the cancer with pathological stage I disease. Therefore, identifying factors predictive of high‐risk pathological recurrence is important. However, few studies have examined the genetic status of these tumors and its relationship to prognosis. Materials and Methods A cohort of 328 cases of primary lung cancer that underwent complete resection at Tokyo Medical and Dental University (TMDU) was screened for 440 cancer‐associated genes using panel testing. Further analyses included 92 cases of pathological stage I NSCLC who did not receive adjuvant chemotherapy. Ridge regression was performed to identify association studies mutational status and postoperative recurrence. These data were then validated using clinical and genetic data from 56 patients in The Cancer Genome Atlas (TCGA). Results Mutations in TP53 , RAS signaling genes KRAS and HRAS , and EGFR were recurrently detected. Ridge regression analysis relevant to recurrence, as well as survival analysis, performed using data from the TMDU cohort revealed significantly shorter relapse‐free survival (RFS) for patients with RAS signaling or TP53 gene mutations than for those without (log‐rank test, p = 0.00090). This statistical trend was also suggested in the TCGA cohort (log‐rank test, p = 0.10). Conclusion Mutations in RAS signaling genes and/or TP53 could be useful for the prediction of shorter RFS of patients with stage I NSCLC.

Objective To compare the microbiota between cholesteatoma and chronic suppurative otitis media (COM) and to identify potential pathogens that explain the relevant phenotypes of cholesteatoma. Study Design Prospective cohort study. Methods Surgical specimens collected from 20 cholesteatomas and nine COMs were treated to dissolve biofilms and subjected to 16S ribosomal RNA (rRNA) gene sequencing and amplicon sequence variant‐level analysis for microbiota profiling and quantitative comparison. Correlations between the relative abundance of potential pathogens and the volume of the primary resected cholesteatomas were examined. Results Differences in bacterial composition (beta diversity) were observed between cholesteatomas and COM ( p = .002), with a higher abundance of Staphylococcus in cholesteatomas than in COM ( p = .005). Common genera in the external auditory canal (EAC) flora, such as Staphylococcus , Corynebacterium , and Cutibacterium , were predominant in both cholesteatoma and COM; Staphylococcus aureus and Pseudomonas aeruginosa were increased in both diseases compared with the EAC flora. Furthermore, coagulase‐negative staphylococci (CoNS) were more abundant in cholesteatomas than in COM ( p = 0.002). Linear discriminant analysis coupled with effect size measurements (LEfSe) identified four CoNS as potential biomarkers for cholesteatoma. The relative abundance of S. aureus , a potential pathogen, was positively correlated with cholesteatoma volume ( r = .60, p = .02). Conclusion The microbiota of cholesteatoma and COM originated from EAC flora, but the bacterial composition was largely altered. Our results suggested that S. aureus infection is involved in cholesteatoma progression. Level of Evidence 3b