Multicenter retrospective study of nivolumab for recurrent/metastatic oral squamous cell carcinoma.

OBJECTIVES: Immunotherapy with nivolumab for patients with recurrent/metastatic oral squamous cell carcinoma has not been evaluated. Here, we aimed to examine the efficacy, safety, and prognostic factors of nivolumab in these patients. MATERIALS AND METHODS: This multicenter retrospective observational study involved patients who received nivolumab between April 2017 and June 2019. The patient characteristics were evaluated for association with progression-free and overall survival. Progression-free and overall survival rates were calculated; parameters that were significant in the univariate analysis were used as explanatory variables. Independent factors for progression-free and overall survival were identified using multivariate analysis. RESULTS: Totally, 143 patients were included. The overall response and disease control rates were 27.3% and 46.2%, respectively. The median, 1- and 2-year progression-free survival rates were 2.7 months, 25.4%, and 19.2%, respectively; those for overall survival were 11.2 months, 47.3%, and 33.6%, respectively. The independent factors affecting progression-free survival were performance status and immune-related adverse event occurrence, whereas those affecting overall survival were performance status, target disease, and number of previous lines of systemic cancer therapy. Eight patients reported grade ≥3 immune-related adverse events. CONCLUSION: Nivolumab was effective for recurrent/metastatic oral squamous cell carcinoma treatment and was well tolerated by patients.

Reconsideration of three screening tests for dysphagia in patients with cerebrovascular disease performed by non-expert examiners.

Dysphagia prevalence has increased with increasing elderly population worldwide. Therefore, early detection of dysphagia has become increasingly important. Repetitive saliva swallowing test (RSST), modified water swallowing test (MWST), and cervical auscultation, which are convenient for non-experts to assess eating and swallowing and have been frequently used in Japan since 20 years. Using aspiration and pharyngeal residues, the objective of this study was to elucidate the efficacy of the three screening tests performed by non-experts in patients who had swallowing disorders. In total, 102 patients with cerebrovascular diseases who were suspected of having dysphagia were assessed. A swallowing team assessed their swallowing capabilities; videofluoroscopy and screening tests were performed. RSST, MWST, and cervical auscultation were performed by junior dentists who were non-experts in dysphagia. Sensitivity, specificity, positive predictive value, negative predictive value, positive likelihood ratio, and negative likelihood ratio in each examination were evaluated using results of aspiration in videofluoroscopy and pharyngeal residues. For aspiration, the highest sensitivity with cervical auscultation (VES) was 93.7%. For pharyngeal residue, the highest sensitivity with cervical auscultation (VES) was 84.3%. For piriform sinus residue, the highest sensitivity with cervical auscultation (VES) was 86.4%. Despite being evaluated by a non-expert, the sensitivity of cervical auscultation (VES) and MWST was ≥ 80%, suggesting their effectiveness as prescreening tests, although the range of specificity was 25.5-68.4% in all examinations. These tests are easy to perform and useful to screen for aspiration or pharyngeal residues before precision tests.

Feasibility of oral microbiome profiles associated with oral squamous cell carcinoma.

Objective: Recently, the possibility that oral microbiomes is associated with oral squamous cell carcinoma (OSCC) initiation and progression has attracted attention; however, this association is still unclear. Here, we comprehensively analyze the microbiome profiles of saliva samples using next-generation sequencing followed by determining the association between oral microbiome profiles and OSCC. Materials and Methods: Microbiome profiles in saliva samples from patients with OSCC, oral leukoplakia (OLK), and postoperative OSCC (Post) were analyzed. Candidate OSCC-associated bacteria were identified by comparing the bacterial diversity and relative abundance of each group based on these microbiome profiles, and their applicability as OSCC detection tools were evaluated. Results: There were significant differences in genus abundances (Streptococcus, Aggregatibacter, and Alloprevotella) among the groups from saliva samples. In the OSCC group, compared with the OLK and Post groups, abundances of the genus Fusobacterium, phylum Fusobacteria and phylum Bacteroidetes were markedly increased and that of the genus Streptococcus and phylum Firmicutes were decreased. Conclusion: The results suggested a strong association of these bacteria with OSCC. Especially, phylum Fusobacterium was significantly associated with early recurrence of OSCC. Thus, oral microbiome analysis may have a potential of novel OSCC detection and prognostic tool.

Salivary CCL20 Level as a Biomarker for Oral Squamous Cell Carcinoma.

BACKGROUND/AIM: This study investigated the utility of C-C motif chemokine ligand 20 (CCL20) expression in saliva as a biomarker for oral squamous cell carcinoma (OSCC) and also examined the associated microbiome. MATERIALS AND METHODS: The study group included patients with OSCC or oral potentially malignant disorder (OPMD), and healthy volunteers (HVs). microarray and qRT-PCR were used to compare salivary CCL20 expression levels among groups. Data on CCL20 levels in oral cancer tissues and normal tissues were retrieved from a public database and examined. Furthermore, next-generation sequencing was used to investigate the salivary microbiome. RESULTS: A significant increase in the expression level of CCL20 was observed in both OSCC tissues and saliva from patients with oral cancer. Fusobacterium was identified as the predominant bacteria in OSCC and correlated with CCL20 expression level. OSCC screening based on salivary CCL20 expression enabled successful differentiation between patients with OSCC and HVs. CONCLUSION: CCL20 expression may be a useful biomarker for OSCC.

Salivary CPLANE1 Levels as a Biomarker of Oral Squamous Cell Carcinoma.

BACKGROUND/AIM: This study aimed to identify novel biomarkers for oral squamous cell carcinoma (OSCC) screening to improve the survival rate of patients with oral cancer. MATERIALS AND METHODS: We investigated differential salivary gene expression in patients with OSCC, those with oral potentially malignant disorders (OPMDs), and healthy volunteers (HVs). CPLANE1 was selected for further investigation by microarray analysis. We used quantitative reverse transcription PCR (qRT-PCR) to determine CPLANE1 expression levels in the saliva. The expression of CPLANE1 in normal and oral cancer tissues was analyzed using the Gene Expression database of Normal and Tumor tissues. RESULTS: qRT-PCR analysis of saliva samples showed that CPLANE1 expression levels were significantly higher in OSCC patients than in HVs and OPMDs patients. Furthermore, we developed a screening test for OSCC using CPLANE1 and showed that it had good accuracy. CONCLUSION: Salivary CPLANE1 could be a useful biomarker for OSCC screening and early detection.

Salivary NUS1 and RCN1 Levels as Biomarkers for Oral Squamous Cell Carcinoma Diagnosis.

BACKGROUND/AIM: Oral cancer may become advanced because of delay in diagnosis. In order to promote oral cancer screening, simple and highly reliable screening methods that can be implemented at general dental clinics are required. Herein we investigated differential salivary gene expression between oral squamous cell carcinoma (OSCC) patients and healthy volunteers (HV) to identify new biomarkers for OSCC detection. MATERIALS AND METHODS: Candidate genes were selected by microarrays, nuclear undecaprenyl pyrophosphate synthase 1 (NUS1) and reticulocalbin 1 (RCN1) were selected for further investigation. We used real-time quantitative reverse transcription PCR (qRT-PCR) to determine NUS1 and RCN1 expression levels in saliva and tissues. RESULTS: qRT-PCR analysis of clinical samples revealed that OSCC patients had significantly higher expression of salivary NUS1 and RCN1 than HV. CONCLUSION: A combination of NUS1 and RCN1 accurately distinguished patients from controls, and this combination can be implemented as a screening test for OSCC.

Changes in oral microbial profiles associated with oral squamous cell carcinoma vs leukoplakia.

AIM: Oral squamous cell carcinoma (OSCC) is the most frequently occurring cancer among head and neck SCC worldwide. The identification of novel effective biomarkers for early detection may greatly improve the survival rate and prognosis of patients with OSCC. This study aimed to identify specific oral microbial profiles associated with OSCC. METHODS: Saliva samples were collected from oral leukoplakia (OLK) and OSCC patients (N = 6 each) and healthy controls (HC; N = 4). Total bacterial genomic DNA was isolated and 16S rRNA gene survey was performed by next-generation sequencing of the V4 region. The relative distribution of abundance for phylogenetic groups was compared among the OSCC and OLK groups. RESULTS: The 448 operational taxonomic units detected from the libraries were classified into 133 genera, 69 families, 41 orders, 26 classes and 12 phyla. The abundance of phyla Bacteroidetes and genus Solobacterium was notably higher in the OSCC group when compared with the OLK group, whereas those of genus Streptococcus was significantly lower in the OSCC group when compared with the OLK. CONCLUSION: These changes in the salivary microbiome may have potential applications as a novel diagnostic tool for the early detection of OSCC.

Bare bone graft with vascularised iliac crest for mandibular reconstruction.

BACKGROUND: "Bare bone graft" with a vascularised iliac crest is a procedure involving no soft tissue for intraoral lining, and the intraoral defect is covered with epithelial cells through secondary healing of the exposed bone. METHODS: A vascularised iliac crest flap is transferred to a segmental mandibular defect intraorally in the position of the osteotomized stump upwardly. Granulation tissue is usually observed on the stump of the bone graft about 1 week after surgery. When sufficient granulation is observed after approximately 4 weeks, "resurfacing" is performed to prevent interference of hypergranulation tissue with epithelization. Resurfacing involves wiping the granulation tissue from the surface of the bone and covering with a plastic prosthesis fitted to the alveolus. RESULTS: A total of 11 patients underwent bare bone graft with a vascularised iliac crest. Resurfacing was performed at an average of 2.1 times for each patient. All wounds in the oral cavity were completely epithelialized from 2 weeks to 3 months after surgery. Complications with the recipient side occurred in four patients. CONCLUSIONS: Bare bone graft with the iliac crest is one favourable option for mandibular reconstruction utilising the particular shape of the bone without the attached soft tissue.

Identification of specific autoantigens in Sjögren's syndrome by SEREX.

We carried out SEREX (serological analysis of antigens by recombinant cDNA expression cloning) using sera from patients with Sjögren's syndrome (SjS) and investigated the frequencies of autoantibodies against autoantigens identified by SEREX in the sera of healthy individuals (HI) and patients with SjS, rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE). IFI16 and two kelch-like proteins, KLHL12 and KLHL7, were found to be novel autoantigens in SjS by SEREX. A markedly high frequency of anti-IFI16 autoantibodies was observed in the sera of SjS (SjS, 70%; RA, 13%; SLE, 33%; HI, 0%). Interestingly, all serum samples from SjS demonstrated immunoreactivity against one or both of IFI16 and SS-B/La. The presence of autoantibodies against KLHL12 and KLHL7 in the sera was significantly specific to SjS (23% and 17%, respectively), as they were not detected in RA, SLE or HI. Furthermore, we confirmed that transcripts of these autoantigens were expressed preferentially in the salivary glands and immuno-privileged testes. Our results suggest these autoantigens may be useful as serological markers for the clinical diagnosis of SjS and may play a crucial role as organ-specific autoantigens in the aetiopathogenesis of SjS. This study warranted clinical evaluations of autoantibodies against IFI16, KLHL12 and KLHL7 in combination with anti-SS-B/La autoantibodies.