The aim of the present study was to characterize the metabolic systems in Japanese patients with oral squamous cell carcinoma (OSCC) using capillary electrophoresis-mass spectrometry (CE-MS) metabolome analysis of saliva samples. A previous study showed variations among ethnicities and tumor sites in the saliva metabolome of patients with OSCC using CE-MS. In the present study, saliva was obtained from 22 Japanese patients with OSCC and from 21 healthy controls who visited the Department of Dentistry, Oral and Maxillofacial Surgery, Tokyo Dental Collage Ichikawa General Hospital, Tokyo, Japan, and all samples were subject to comprehensive quantitative metabolome analysis using CE-MS. A total of 499 metabolites were detected as CE-MS peaks in the saliva tested from the two groups. A total of 25 metabolites were revealed as potential markers to discriminate between patients with OSCC and healthy controls: Choline, p-hydroxyphenylacetic acid, and 2-hydroxy-4-methylvaleric acid (P<0.001); valine, 3-phenyllactic acid, leucine, hexanoic acid, octanoic acid, terephthalic acid, γ-butyrobetaine, and 3-(4-hydroxyphenyl)propionic acid (P<0.01); and isoleucine, tryptophan, 3-phenylpropionic acid, 2-hydroxyvaleric acid, butyric acid, cadaverine, 2-oxoisovaleric acid, N6,N6,N6-trimethyllysine, taurine, glycolic acid, 3-hydroxybutyric acid, heptanoic acid, alanine, and urea (P<0.05, according to the Wilcoxon rank sum test). A previous study by Sugimoto and co-workers detected 24 discriminatory metabolites, 7 of which (taurine, valine, leucine, isoleucine, choline, cadaverine, and tryptophan) were also detected in the present study. In the present study, however, choline, metabolites in the branched chain amino acids (BCAA) cycle, urea, and 3-hydroxybutyric acid were also characterized. Choline and metabolites of the BCAA cycle have previously been reported in OSCC using metabolome analysis. To the best of our knowledge, no previous reports have identified urea and 3-hydroxybuyric acid in the metabolome of patients with OSCC. These findings suggest the usefulness of metabolites as salivary biomarkers for Japanese patients with OSCC. Further studies using larger patient cohorts should be conducted to validate these results.

Background: Oral cancer screening is important for early detection and early treatment, which help improve survival rates. Biopsy is the gold standard for a definitive diagnosis but is invasive and painful, while fluorescence visualization is non-invasive, convenient, and real-time, and examinations can be repeated using optical instruments. The purpose of this study was to clarify the usefulness of fluorescence visualization in oral cancer screening. Methods: A total of 502 patients, who were examined using fluorescence visualization with optical instruments in our hospitals between 2014 and 2019, were enrolled in this study. The final diagnosis was performed by pathological examination. Fluorescence visualization was analyzed using subjective and objective evaluations. Results: Subjective evaluations for detecting oral cancer offered 96.8% sensitivity and 48.4% specificity. Regarding the objective evaluations, sensitivity and specificity were 43.7% and 84.6% for mean green value, 55.2% and 67.0% for median green value, 82.0% and 44.2% for coefficient of variation of value, 59.6% and 45.3% for skewness, and 85.1% and 75.8% for value ratio. For the sub-analysis of oral cancer, all factors on objective and subjective evaluation showed no significant difference. Conclusions: Fluorescence visualization with subjective and objective evaluation is useful for oral cancer screening.

Le Fort I osteotomy is one of the surgical procedures now routinely and safely performed. It is possible to move the maxilla in three dimensions, but it is necessary to separate the bones around the maxillary sinus. Therefore, with surgery, maxillary sinus mucosal thickening occurs. By knowing the changes in the sinus mucosa after surgery and the factors affecting it, it is possible to better predict the outcomes of surgery and contribute to safer surgery. In this study, thickening of maxillary sinus mucosa before and after surgery in Le Fort I osteotomy was evaluated using multidetector-row computed tomography (MDCT) images, and the changes in mucosal thickening and the related factors were examined. Using MDCT images, the maxillary sinus mucosa of 125 patients who had undergone Le Fort I osteotomy was retrospectively evaluated before surgery, 1 month after surgery, and 1 year after surgery. On the MDCT images, the maxillary sinus was judged as mucosal thickening and classified into three grades according to the proportion occupying the maxillary sinus. In the evaluation of factors related to mucosal thickening, the following eight factors were examined: sex, age, diagnosis, operating time, amount of postoperative bleeding, with/without bone graft, with/without multisegmental osteotomy, and with/without macrolide therapy after surgery. The mean age at the time of surgery was 25.6 ± 8 years. Of all 125 patients, 66 had bilateral thickening, 19 had unilateral thickening, and 40 had no thickening. Factors that were significantly related to mucosal thickening were the operative time for the maxilla, bone grafts, and macrolide therapy after surgery. Operative time for the maxilla, bone grafts, and macrolide therapy after surgery were found to be related to mucosal thickening. In addition, MDCT scanning 1 month after surgery was considered to be appropriate for evaluation of maxillary sinus mucosal thickening.

Oral fluids (OFs) contain small extracellular vesicles (sEVs or exosomes) that carry disease-associated diagnostic molecules. However, cells generate extracellular vesicles (EVs) other than sEVs, so the EV population is quite heterogeneous. Furthermore, molecules not packaged in EVs can also serve as diagnostic markers. For these reasons, developing a complete picture of particulate matter in the oral cavity is important before focusing on specific subtypes of EVs. Here, we used differential centrifugation to fractionate human OFs from healthy volunteers and patients with oral squamous cell carcinoma into 5 fractions, and we characterized the particles, nucleic acids, and proteins in each fraction. Canonical exosome markers, including CD63, CD9, CD133, and HSP70, were found in all fractions, whereas CD81 and AQP5 were enriched in the 160K fraction, with non-negligible amounts in the 2K fraction. The 2K fraction also contained its characteristic markers that included short derivatives of EGFR and E-cadherin, as well as an autophagosome marker, LC3, and large multi-layered vesicles were observed by electronic microscopy. Most of the DNA and RNA was recovered from the 0.3K and 2K fractions, with some in the 160K fraction. These results can provide guideline information for development of purpose-designed OF-based diagnostic systems.