More than 90% of oral cancers are histopathologically squamous cell carcinomas (SCCs). According to clinical behavior and histopathological features, we hypothesize that oral SCC can originate from either oral squamous epithelium or minor salivary glands. Here, we examined whether some oral SCCs originate from minor salivary glands, and investigated whether these tumors show particularly aggressive biological behavior. The mRNA expression profiles of samples obtained from six patients with oral floor SCC (five men, one woman; mean age, 62.7 years) were analyzed using a microarray containing 32,878 probes. The six samples were divided into two groups by clustering of expression levels of 845 probes differentially expressed in normal oral squamous epithelium and normal salivary glands. The expression profile in four cases was similar to that of normal oral squamous epithelium, and in two cases was similar to that of normal salivary glands. Furthermore, we identified nine genes that reveal the origin of the oral SCC. Subsequently, we examined the expression levels of these nine marker genes by reverse transcriptase‐polymerase chain reaction to determine the origin of 66 oral SCCs. Twelve of the 66 oral SCCs were considered to originate from minor salivary glands, and these tumors showed high metastatic potential (p = 0.044, Chi‐square test). Furthermore, SCC derived from minor salivary glands showed a poor event‐free survival rate (p = 0.017, Kaplan–Meier analysis). In conclusion, determination of the origin of oral SCC is helpful in planning treatment for patients with oral SCC.

Background/Aim: Odontogenic diseases are diagnosed based on clinical course, imaging, and histopathology. However, a definitive diagnosis is not always possible. Patients and Methods: We analyzed whole exons of SMO, BRAF, PTCH1 and GNAS using next-generation sequencing (NGS) in 18 patients. Results: Of the 6 patients with ameloblastoma, 2 patients had the same missense mutation in BRAF, and 1 patient with peripheral ameloblastoma had a missense mutation in PTCH1. Of the 7 patients with odontogenic keratocyst, 4 patients had a missense mutation in PTCH1, 2 patients had missense mutations in BRAF, and 1 patient had a missense mutation in SMO. The patient with odontoma had missense mutations in SMO, BRAF and PTCH1. One patient with cementosseous dysplasia had missense mutations in SMO and PTCH1. The patient with adenomatoid odontogenic tumor had missense mutations in SMO. Conclusion: Whole exome sequencing of the above genes by NGS would be useful for the differential diagnosis of odontogenic diseases.Odontogenic diseases (tumors, cysts and dysplasias) are diagnosed based on clinical course, several X-ray images, and histopathological findings, but a definitive diagnosis is not always possible (1). Odontogenic tumors derive from cells involved in tooth development, and in many cases, it is difficult 3233 This article is freely accessible online.

We evaluated the impact of pharmacist-led heart failure (HF) drug recommendations during hospitalization for hospitalized patients with HF. Hospitalized patients with HF were retrospectively reviewed. Patients were hospitalized before (n = 208, non-intervention group) or after (n = 170, intervention group) the launch of the HF multidisciplinary team (HFMDT) approach with pharmacist-led HF medication optimization. There were no significant group differences in patient background characteristics at admission. Patients with HF with reduced ejection fraction who were not on beta blockers or angiotensin-converting enzyme inhibitor/angiotensin receptor blockers (ACE-I/ARB) at admission were significantly more likely to be on beta blockers at the time of discharge in the intervention group (73.3 vs 96.3%, P = 0.027) compared to those in non-intervention group; however, the change in ACE-I/ARB prescriptions was not significant (53.3 vs 63.3%, P = 0.601). The proportion of patients on any drug with recommendations against its use in patients with HF did not change from admission to discharge in the non-intervention group (21.2 vs. 20.2%, P = 0.855), but was significantly reduced in the intervention group (22.9 vs. 12.9%, P = 0.005). There were no group differences in the in-hospital all-cause mortality (non-intervention, 3.4%; intervention, 2.4%; P = 0.761) or length of hospital stay (median: non-intervention, 13 days; intervention, 14 days; P = 0.508). Pharmacist-led HF drug recommendations during hospitalization as part of a HFMDT approach for hospitalized patients with HF can increase beta blocker prescriptions and decrease non-preferred drug prescriptions.

Background: The surveillance methods oral squamous cell carcinoma (OSCC) patients may be chosen by considering the risk for recurrence, and it is important to establish appropriate methods during the period in which latent/dormant cancer cells become more apparent. To investigate the appropriate surveillance of patients with OSCC based on the individual risk for recurrence and/or metastasis, we performed a retrospective cohort study after the complete surgical resection of OSCC as the primary treatment. Methods: The study was performed in 324 patients with OSCC who had been primarily treated with surgery from 2007 to 2020 at our hospital. We investigated the period, timing, and methods (visual examination, palpation and imaging using FDG-PET/CT or CECT) for surveillance in each case that comprised postsurgical treatment. Results: Regarding the time to occurrence of postsurgical events, we found that half of cases of local recurrence, cervical lymph node metastasis, and distant metastasis occurred within 200 days, and 75% of all of these events occurred within 400 days. However, the mean time for second primary cancer was 1589 days. The postsurgical events were detected earlier by imaging examinations than they were by visual examination and palpation. Conclusions: For the surveillance of patients with OSCC after primary surgery, it is desirable to perform FDG-PET/CT within 3–6 months and at 1 year after surgery and to consider CECT as an option in between FDG-PET/CT, while continuing history and physical examinations for about 5 years based on individual risk assessment.

TSC-22 (TGF-β stimulated clone-22) has been reported to induce differentiation, growth inhibition, and apoptosis in various cells. TSC-22 is a member of a family in which many proteins are produced from four different family genes. TSC-22 (corresponding to TSC22D1-2) is composed of 144 amino acids translated from a short variant mRNA of the TSC22D1 gene. In this study, we attempted to determine the intracellular localizations of the TSC22D1 family proteins (TSC22D1-1, TSC-22 (TSC22D1-2), and TSC22(86) (TSC22D1-3)) and identify the binding proteins for TSC22D1 family proteins by mass spectrometry. We determined that TSC22D1-1 was mostly localized in the nucleus, TSC-22 (TSC22D1-2) was localized in the cytoplasm, mainly in the mitochondria and translocated from the cytoplasm to the nucleus after DNA damage, and TSC22(86) (TSC22D1-3) was localized in both the cytoplasm and nucleus. We identified multiple candidates of binding proteins for TSC22D1 family proteins in in vitro pull-down assays and in vivo binding assays. Histone H1 bound to TSC-22 (TSC22D1-2) or TSC22(86) (TSC22D1-3) in the nucleus. Guanine nucleotide-binding protein-like 3 (GNL3), which is also known as nucleostemin, bound to TSC-22 (TSC22D1-2) in the nucleus. Further investigation of the interaction of the candidate binding proteins with TSC22D1 family proteins would clarify the biological roles of TSC22D1 family proteins in several cell systems.

Cervical lymph node metastasis is an important prognostic factor in oral squamous cell carcinoma (OSCC) , and preoperative evaluation of cervical lymph nodes requires high diagnostic accuracy. We investigated the usefulness of FDG-PET/contrast-enhanced CT for diagnosing cervical lymph node metastasis in OSCC and determined which procedures could be additionally performed to improve diagnostic accuracy. Between April 2005 and March 2013, a total of 115 patients with OSCC who were treated in the Department of Oral and Maxillofacial Surgery, Dokkyo Medical University Hospital participated in this study. The primary sites of OSCC were the tongue (n = 66) , mandibular gingiva (n = 27) , maxillary gingiva (n = 10) , floor of the mouth (n = 6) , and buccal mucosa (n = 6) . The clinical stage of the disease was stage I in 10 cases, stage II in 35 cases, stage III in 17 cases, and stage IV in 53 cases. Uptake of FDG was elevated in the cervical lymph nodes of 48 patients, among whom 45 had cervical metastasis (true-positive) and three did not (false-positive) . Among 67 patients who did not have elevated FDG uptake, 8 patients had cervical metastasis (false-negative)and 59 patients did not (true-negative) . The sensitivity, specificity, and accuracy of FDG-PET at a threshold SUVmax of 2.0 were 84.9%, 95.2%, and 90.4%, respectively. A re-evaluation of patients with negative FDG-PET/contrast-enhanced CT findings together with palpation and MRI increased the diagnostic performance to 93.6%, the sensitivity to 94.5%, and the specificity to 94.1% accuracy. In conclusion, FDG -PE T/contrast-enhanced C T was veryuseful for diagnosing cervical lymph node metastasis in OSCC. Furthermore, palpation and MRI combined with FDG-PET/contrast-enhanced CT is recommended to reduce the rate of false-negative findings. : FDG-PET/contrast-enhanced CT (FDG-PET/ 造影 CT) ，oral squamous cell carcinoma (口腔扁平上皮癌) ， cervical lymph node metastasis (頸部リンパ節転移) 1) 獨協医科大学医学部口腔外科学講座 (主任：川又 均教授) 2) 佐野厚生総合病院歯科口腔外科 (主任：和久井崇大部長) 3) 菅間記念病院歯科口腔外科 (主任：齋藤正浩医長) 1)

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Mutations in p53 are common in human oral squamous cell carcinoma (OSCC). However, in previous analyses, only detection of mutant p53 protein using immunohistochemistry or mutations in some exons have been examined. Full length mutant p53 protein in many cases shows a loss of tumor suppressor function, but in some cases possibly shows a gain of oncogenic function. In this study, we investigate relationships of outcomes with the mutational spectrum of p53 (missense and truncation mutations) in whole exon in OSCC. Specimens from biopsy or surgery (67 cases) were evaluated using next-generation sequencing for p53, and other oncogenic driver genes. The data were compared with overall survival (OS) and disease-free survival (DFS) using univariate and multivariate analyses. p53 mutations were detected in 54 patients (80.6%), 33 missense mutations and 24 truncation mutations. p53 mutations were common in the DNA-binding domain (43/52) and many were missense mutations (31/43). Mutations in other regions were mostly p53 truncation mutations. A comparison of cases with p53 mutations (missense or truncation) with wild-type p53 cases showed a significant difference in lymph node metastasis. DFS was significantly poorer in cases with p53 truncation mutations. Cases with p53 truncation mutations increased malignancy. In contrast, significant differences were not found between cases with p53 missense mutations and other mutations. The p53 missense mutation cases might include cases with mostly similar function to that of the wild-type, cases with loss of function, and cases with various degrees of gain of oncogenic function.