Combined external radiotherapy and single-fraction palliative high-dose-rate interstitial brachytherapy for a patient with a base of tongue cancer who had a previous radiation history.

Only a few studies have explored whether high-dose-rate interstitial brachytherapy (HDR-ISBT) can be indicated as a palliative/symptomatic treatment. We present the good results of palliative treatment using HDR-ISBT combined with external beam radiotherapy (ERT) in a patient of base of tongue cancer (cT4aN1M0). The patient was an 81-year-old male who complained of local pain. He had a previous irradiation history for head and neck cancer receiving ERT with systemic chemotherapy and radical surgery 15 years ago. Since it might be difficult for him to receive radical radiation doses using ERT alone, palliative ERT of relatively lower doses of 37.5 Gy in 15 fractions was selected. One month after ERT, HDR-ISBT was implemented as a booster. Considering the burden on physical condition, single-fraction HDR-ISBT was selected. We employed a new technique in which we did not penetrate the ventral surface of the tongue to reduce the risk of infection and bleeding. The planning-aim dose was 9.5 Gy. The dose that covered 90% of the clinical target volume was 9.6 Gy. The treatment ended without any problems. Acute complications were not observed. The tumor size decreased, and local pain disappeared at post-treatment day 84. No late complications were observed. Two years and 8 months after the treatment, the patient is alive without any obvious recurrence. Additional single-fraction HDR-ISBT boost may be a useful modality as a palliative/symptomatic intent. The implantation technique and dose-fraction schedule may be important for the safe treatment of older patients or those with poor performance status.

Efficacy of Minor Salivary Glands as Indicators of Depth of Resection for Superficial Hypopharyngeal Carcinoma.

Objective: This study aimed to investigate the utility of minor salivary glands in the hypopharynx as novel indicators for safe resection of superficial hypopharyngeal carcinomas with fewer complications. Study Design: Cadaveric study. Setting: Cadavers were stored in the pathology laboratory at Kansai Medical University. Methods: Twenty-three cadaveric specimens were examined for minor salivary glands in the pyriform sinus, posterior wall, and postcricoid regions of the hypopharynx. Their count, size, and depth were assessed. Resected specimens from 5 consecutive patients with superficial hypopharyngeal carcinomas were pathologically analyzed to determine the positional relationship between cancer and minor salivary glands. Results: Minor salivary glands were present in more than 70% of patients in each region during autopsy, with the postcricoid region having a larger count and size. The glands were universally present, regardless of sex, height, or body mass index. Minor salivary glands in the pyriform sinus and postcricoid region were present at a depth of 30% from the bottom of the submucosal layer, whereas those in the posterior wall were present in the shallow muscularis. During surgery, endoscopic findings revealed minor salivary glands as small white nodules in the submucosal layer. Pathological examination of the resected specimen confirmed that the white nodule was a minor salivary gland. In addition, tumor position in relation to minor salivary glands provided an adequate margin for resection. Conclusion: Minor salivary glands may serve as reliable indicators for determining adequate deep safety margins during surgery for superficial hypopharyngeal carcinoma.

Clinical, genomic and immune microenvironmental determinants of nivolumab response in head and neck squamous cell carcinoma.

Background: In view of improving biomarkers predicting the efficacy of immunotherapy for head and neck squamous cell carcinoma (R/M HNSCC), this multicenter retrospective study aimed to identify clinical, tumor microenvironmental, and genomic factors that are related to therapeutic response to the anti- Programmed cell death protein 1 (PD-1) antibody, nivolumab, in patients with R/M HNSCC. Methods: The study compared 53 responders and 47 non-responders, analyzing formalin-fixed paraffin-embedded samples using 14-marker multiplex immunohistochemistry and targeted gene sequencing. Results: Of 100 patients included, responders had significantly lower smoking and alcohol index, higher incidence of immune related adverse events, and higher PD-1 ligand (PD-L1) expression in immune cells as well as PD-L1 combined positive score (CPS) than non-responders. The frequency of natural killer cells was associated with nivolumab response in patients with prior cetuximab use, but not in cetuximab-naïve status. Age-stratified analysis showed nivolumab response was linked to high CPS and lymphoid-inflamed profiles in patients aged ≥ 65. In contrast, lower NLR in peripheral blood counts was associated with response in patients aged < 65. Notably, TP53 mutation-positive group had lower CPS and T cell densities, suggesting an immune-excluded microenvironment. Patients with altered tumor suppressor gene pathways, including TP53, CDKN2A, and SMAD4 mutations, had lower CPS, higher smoking index, and were associated with poor responses. Conclusion: Nivolumab treatment efficacy in HNSCC is influenced by a combination of clinical factors, age, prior treatment, immune environmental characteristics, and gene mutation profiles.

Preliminary investigation of endoscopic surgery for tympanic membrane perforation: Regenerative treatment compared with conventional surgery.

PURPOSE: To compare surgical outcomes of regenerative treatment (RT) including basic fibroblast growth factor (bFGF) (Group-R) with the conventional method (Group-C) for patients with tympanic membrane perforation (TMP), both of whom underwent transcanal endoscopic ear surgery. METHODS: The study population of Group-R included 61 ears of 59 patients treated with RT-TMP in which TMP edges were disrupted mechanically and a gelatin sponge immersed in bFGF was inserted into the TMP. Fibrin glue was then dripped over the sponge. Group-C consisted of 13 patients who underwent conventional surgery before adopting the RT-TMP. Patients' characteristics and outcomes including TMP closure rates, and change in hearing level were evaluated three or more weeks after the surgery. RESULTS: The baseline characteristics including size of TMP were not significantly different between the two groups. Although Group-R had significantly shorter operating time than Group-C, the complete TMP closure rates were 69 % (9/13) and 85 % (52/61), respectively. Air-conduction hearing thresholds showed significant improvements, and analysis of variance showed that Group-R achieved significant interactions other than at 8 kHz, implying better improvement in cases with TMP closure. The air-bone gaps also improved at all frequencies in both groups. Specifically, at 4 kHz, there was a trend showing better improvement in Group-R. CONCLUSION: RT-TMP had a high TMP closure rate and good hearing improvement, with no significant differences compared with those of conventional surgery. This new therapy is simple and safe, and requires less operating time, and it could help improve the quality of life of patients with TMP.

Safety of immune checkpoint inhibitors in patients aged over 80 years: a retrospective cohort study.

BACKGROUND: Immuno-oncology (IO) drugs are essential for treating various cancer types; however, safety concerns persist in older patients. Although the incidence of immune-related adverse events (irAEs) is similar among age groups, higher rates of hospitalization or discontinuation of IO therapy have been reported in older patients. Limited research exists on IO drug safety and risk factors in older adults. Our investigation aimed to assess the incidence of irAEs and identify the potential risk factors associated with their development. METHODS: This retrospective analysis reviewed the clinical data extracted from the medical records of patients aged > 80 years who underwent IO treatment at our institution. Univariate and multivariate analyses were performed to assess the incidence of irAEs. RESULTS: Our study included 181 patients (median age: 82 years, range: 80-94), mostly men (73%), with a performance status of 0-1 in 87% of the cases; 64% received IO monotherapy. irAEs occurred in 35% of patients, contributing to IO therapy discontinuation in 19%. Our analysis highlighted increased body mass index, eosinophil counts, and albumin levels in patients with irAEs. Eosinophil count emerged as a significant risk factor for any grade irAEs, particularly Grade 3 or higher, with a cutoff of 118 (/µL). The group with eosinophil counts > 118 had a higher frequency of irAEs, and Grade 3 or higher events than the group with counts ≤ 118. CONCLUSION: IO therapy is a safe treatment option for patients > 80 years old. Furthermore, patients with elevated eosinophil counts at treatment initiation should be cautiously managed.

CD69 Signaling in Eosinophils Induces IL-10 Production and Apoptosis via the Erk1/2 and JNK Pathways, Respectively.

INTRODUCTION: Eosinophils contribute to the pathogenesis of allergic diseases, including asthma, allergic rhinitis, and atopic dermatitis. We previously reported that human tissue eosinophils have high CD69 expression compared to blood eosinophils, and its expression is correlated with disease severity and the number of infiltrated eosinophils. However, biological CD69 signaling activity in eosinophils remains unclear. METHODS: CD69 expression on lung tissue eosinophils obtained from mice with ovalbumin-induced asthma was measured using flow cytometry. CD69 crosslinking was performed on eosinophils purified from the spleen of IL-5 transgenic mice to investigate CD69 signaling and its function in eosinophils. Then, qPCR, Western blot, enzyme-linked immunosorbent assay, and survival assay results were analyzed. RESULTS: Surface CD69 expression on lung tissue eosinophils in the asthma mice model was 2.91% ± 0.76%, whereas no expression was detected in the healthy group. CD69-expressed eosinophils intrinsically have an upregulation of IL-10 mRNA expression. Moreover, CD69 crosslinking induced further pronounced IL-10 production and apoptosis; these responses were mediated via the Erk1/2 and JNK pathways, respectively. CONCLUSIONS: Our results suggested that CD69+ eosinophils play an immunoregulator role in type 2 inflammation, whereas activated tissue eosinophils contribute to the pathogenesis of asthma.

The Neutralization of the Eosinophil Peroxidase Antibody Accelerates Eosinophilic Mucin Decomposition.

Eosinophilic airway inflammation, complicated by bronchial asthma and eosinophilic chronic rhinosinusitis (ECRS), is difficult to treat. The disease may become refractory when eosinophilic mucin associated with eosinophil peroxidase (EPX) and autoantibodies fills in the paranasal sinus and small airway. This study investigated the functional role of an anti-EPX antibody in eosinophilic mucin of ECRS in eosinophilic airway inflammation. Eosinophilic mucin was obtained from patients with ECRS. The effects of the anti-EPX antibody on dsDNA release from eosinophils and eosinophilic mucin decomposition were evaluated. Immunofluorescence or enzyme-linked immunosorbent assays were performed to detect the anti-EPX antibody and its supernatant and serum levels in eosinophilic mucin, respectively. The serum levels of the anti-EPX antibody were positively correlated with sinus computed tomography score and fractionated exhaled nitrogen oxide. Patients with refractory ECRS had higher serum levels of the anti-EPX antibody than those without. However, dupilumab treatment decreased the serum levels of the anti-EPX antibody. Immunoglobulins (Igs) in the immunoprecipitate of mucin supernatants enhanced dsDNA release from eosinophils, whereas the neutralization of Igs against EPX stopped dsDNA release. Furthermore, EPX antibody neutralization accelerated mucin decomposition and restored corticosteroid sensitivity. Taken together, the anti-EPX antibody may be involved in the formulation of eosinophilic mucin and be used as a clinical marker and therapeutic target for intractable eosinophilic airway inflammation.

Postoperative hemorrhage after Le Fort I osteotomy hemostasis with angiographic embolization: report of two cases.

This study reported two cases of acute life-threatening hemorrhage after Le Fort I osteotomy. In both cases, computed tomography and angiography revealed damage to the descending palatine artery, which was successfully treated by angiographic embolization. Although massive hemorrhage after Le Fort I osteotomy is rare, acute hemorrhage from the postoperative area may occur. Angiographic embolization is useful in cases of such hemorrhage from the posterior nasal cavity where endoscopic hemostasis is not possible.

Direct specimen collection during routine operation improves nucleic acid quality in genetic analysis samples for head and neck tumors: A retrospective study.

The nucleic acid integrity of head and neck squamous cell carcinoma (HNSCC) samples is poor, and the material available for genetic analysis is limited. Therefore, to expand the effectiveness of personalized medicine in patients with HNSCC, a new sampling method is needed. In total, 128 samples from 44 patients with HNSCC were studied: 32 genetic analysis samples (GASs) collected as 5 × 5 × 5 mm tissue fragments from resected large tumors and immediately embedded in a small formalin bottle within 10 min (i.e., the ischemic time), 43 primary tumor components (primary), 14 decalcified tumor (DC) samples, 32 metastatic tumors in lymph nodes (LNs), and 7 parakeratinized components (PKCs). The nucleic acid quality in the GAS, primary, DC, LN, and PKC groups was compared and next-generation sequencing (NGS) was performed. DNA integrity number and percentage of RNA fragments with > 200 nucleotides were significantly higher in the GAS group than those in the other groups. RNA integrity number decreased first in LN, followed by GAS, primary, and DC. No significant differences were observed in DIN, RIN and DV200 among the PKC, primary and LN. Following methyl green-pyronin staining, preserved DNA and RNA were not visualized in DC samples. Most NGS metrics did not differ significantly among primary, LN, and PKC samples. In conclusion, GASs should be collected during routine hospital activities. When the volume of viable materials is limited, PKCs should be considered for genetic analysis.

Identification of Risk Factors for Mortality and Prolonged Hospitalization in Patients Treated With Surgical Drainage for Otogenic Intracranial Complications: A Nationwide Study Using a Japanese Inpatient Database.

OBJECTIVE: Data on risk factors for otogenic intracranial complications including cerebral abscess have been limited. Using a nationwide database, the aim was to identify the factors related to mortality and delayed discharge. STUDY DESIGN: Retrospective. SETTING: Nationwide database using the Diagnostic Procedure Combination database. MAIN OUTCOME MEASURES: Data of 145 patients were extracted from a Japanese inpatient database between 2012 and 2020. The main outcome was survival at discharge. In a subgroup analysis of the 137 surviving patients, the second outcome was delayed discharge. RESULTS: The mortality rate was 5.5% (8 of 145). Logistic regression analyses identified intracerebral complications (adjusted odds ratio [OR], 3.09) and more than 2-day delay of the first surgery after admission (adjusted OR, 4.68) as risk factors for mortality. Specifically, consciousness level evaluated by the Japan Coma Scale (JCS) was significantly related to prolonged hospitalization or mortality: JCS I (adjusted OR, 3.40) and JCS ≥II (adjusted OR, 25.1). CONCLUSIONS: Although otogenic intracranial complications are rare, and their mortality is decreasing because of the progress in imaging and clinical strategies, they remain the most severe complications of suppurative otitis media and/or cholesteatoma. Consciousness level at admission, comorbid diabetes mellitus, and a greater than 2-day delay of surgical intervention were related to prolonged hospitalization or mortality.

Head and Neck Solitary Fibrous Tumor Presenting as Salivary Gland Tumor: Two Case Reports and Review of the Literature.

Solitary fibrous tumors (SFTs) are soft tumors (mesenchymal origin) that most likely develop from adult mesenchymal stem cells. SFTs are not common in the head and neck region, and the characteristics of tumors in this location are unclear. The present study describes the clinicopathological findings of 2 cases of SFTs arising in the parotid gland and buccal space, presenting as salivary gland tumors. The first case is a 76-year-old man presenting with a painless tumor on the right parotid gland who subsequently underwent partial superficial parotidectomy. According to the results of histopathological analysis, the tumor consisted of stellate and spindle-shaped cells proliferating on a mucous-like substrate. Immunohistochemical staining revealed that neoplastic cells were positive for CD34, vimentin, Bcl2, and STAT6. The second case is of a 64-year-old man presenting with a painless lump on his right cheek. Based on the findings of fine needle aspiration cytology, a tumor derived from myoepithelial cells of the minor salivary gland or a nonepithelial tumor was suspected. The patient underwent surgical resection via an intraoral approach. Histopathologically, the tumor consisted of spindle-shaped cells with rod-shaped or irregular nuclei. Immunohistochemical staining revealed that the neoplastic cells were positive for CD34, CD99, Bcl2, and STAT6. Briefly, SFT should be considered in the differential diagnosis of a well-marginalized lesion in the salivary gland and oral cavity. STAT6 immunohistochemistry is the most specific and sensitive method of diagnosing SFT. A thorough understanding of the morphological changes associated with SFT and their correlation with clinical, immunohistochemical, and molecular characteristics is important to avoid misdiagnosis.

Inoculation of lymphocytes from young mice prevents progression of age-related hearing loss in a senescence-associated mouse model.

Despite the increase in age-related hearing loss (ARHL) prevalence owing to increased population aging, preventive measures against ARHL have not yet been established. The immune system becomes one of the most dysfunctional systems upon aging, and immunosenescence greatly affects homeostasis and promotes systemic aging along with chronic inflammation and oxidative stress. This study aimed to determine whether immuno-rejuvenation procedures can prevent ARHL and have clinical applications as well as to analyze the communication mechanisms between the systemic immune system and the cochlea using a murine model. Lymphocytes from young mice inhibited the progression of ARHL. The method of cryopreserving these lymphocytes and inoculating them at the onset of ARHL suggests their clinical application. Mice that were administered this treatment not only maintained auditory threshold but also avoided spinal ganglion degeneration, cellular immune aging, and nitric oxide production, which causes age-related tissue damage. These findings coincide with our previous strategies against immunosenescence and neuronal aging. Therefore, the manipulation of systemic immune function may contribute not only to the prevention of ARHL but also to the development of novel anti-aging clinical measures, paving the way to healthy longevity with preserved organ function.

MMP14 expression levels accurately predict the presence of extranodal extensions in oral squamous cell carcinoma: a retrospective cohort study.

BACKGROUND: Extranodal extension (ENE) is an adverse prognostic factor for oral squamous cell carcinoma (OSCC), and patients with OSCC along with ENE require neck dissection. In this study, we developed a novel ENE histology-based pathological predictor using MMP14 expression patterns in small biopsy specimens. METHODS: A total of 71 surgically resected tissue, 64 dissected lymph node (LN), and 46 biopsy specimens were collected from 71 patients with OSCC. Immunohistochemical analyses of total MMP14 expression in the tumour nest and cancer-associated fibroblasts (CAFs) were performed using the MMP14 co-scoring system (high- or low-risk). The association analysis of MMP14 expression in metastatic LNs was performed with respect to the presence and absence of ENE. Clinicopathological analyses and multivariate examinations were performed to assess the risks of metastasis and ENE presence. The predictive value of ENE and the impact of ENE and MMP14 expression on 5-year overall survival were examined. RESULTS: High-risk MMP14 expression was detected in metastatic LN specimens with ENE. MMP14 expression in tumour nests and CAFs and its overexpression at the tumour-stromal interface significantly correlated with the presence of ENE. The MMP14 co-scoring system was an independent risk predictor for ENE, with sensitivity, specificity, and accuracy of over 80% in biopsy samples; patients with a high risk in the MMP14 co-scoring system had significantly worse prognoses in both resections and biopsies. CONCLUSION: The MMP14 co-scoring system accurately predicted ENE presence and poor prognosis via immunohistochemical evaluation of small biopsies. This system is a simple, accurate, and inexpensive immunohistochemical approach that can be used in routine pathological diagnosis for effective treatment planning.

Omalizumab is effective for a patient with pollen-food allergy syndrome who experienced intractable lip edema.

Pollen-food allergy syndrome (PFAS) is an immunoglobulin E (IgE)-mediated allergic reaction caused when patients with pollen allergy ingest food having cross-reactivity with pollen. To date, no effective treatment method for this has been established. Here we report the case of a patient with PFAS who experienced lip edema, causing difficulties in treatment. This report describes the case of a 12-year-old boy with perennial allergic rhinitis since the age of 8 years. After ingesting fresh fruits and raw vegetables at the age of 11 years, he started to experience lip edema repeatedly. Thus, the patient was referred to our department. Based on the results of serum antigen-specific IgE, prick-to-prick, and allergen component tests, he was diagnosed with PFAS. He has been instructed to avoid causative food. Furthermore, the treatment using an antihistamine and antileukotriene receptor antagonist was initiated for pollen allergy. Sublingual immunotherapy (SLIT) for Japanese cedar pollen was initiated because the patient experienced severe nasal allergy symptoms during the dispersal season of this pollen. These treatments alleviated the nasal symptoms; however, the lip edema persisted. Omalizumab administration improved the lip edema. The combination of SLIT and omalizumab may be an effective treatment option for patients with PFAS.

CCL4 Regulates Eosinophil Activation in Eosinophilic Airway Inflammation.

Eosinophilic chronic rhinosinusitis (ECRS) is a refractory airway disease accompanied by eosinophilic inflammation, the mechanisms of which are unknown. We recently found that CCL4/MIP-1ß-a specific ligand for CCR5 receptors-was implicated in eosinophil recruitment into the inflammatory site and was substantially released from activated eosinophils. Moreover, it was found in nasal polyps from patients with ECRS, primarily in epithelial cells. In the present study, the role of epithelial cell-derived CCL4 in eosinophil activation was investigated. First, CCL4 expression in nasal polyps from patients with ECRS as well as its role of CCL4 in eosinophilic airway inflammation were investigated in an in vivo model. Furthermore, the role of CCL4 in CD69 expression-a marker of activated eosinophils-as well as the signaling pathways involved in CCL4-mediated eosinophil activation were investigated. Notably, CCL4 expression, but not CCL5, CCL11, or CCL26, was found to be significantly increased in nasal polyps from patients with ECRS associated with eosinophil infiltration as well as in BEAS-2B cells co-incubated with eosinophils. In an OVA-induced allergic mouse model, CCL4 increased eosinophil accumulation in the nasal mucosa and the bronchoalveolar lavage (BALF). Moreover, we found that CD69 expression was upregulated in CCL4-stimulated eosinophils; similarly, phosphorylation of several kinases, including platelet-derived growth factor receptor (PDGFR)ß, SRC kinase family (Lck, Src, and Yes), and extracellular signal-regulated kinase (ERK), was upregulated. Further, CCR5, PDGFRß, and/or Src kinase inhibition partially restored CCL4-induced CD69 upregulation. Thus, CCL4, which is derived from airway epithelial cells, plays a role in the accumulation and activation of eosinophils at inflammatory sites. These findings may provide a novel therapeutic target for eosinophilic airway inflammation, such as ECRS.

Efficacy of Combination Therapy with Lenvatinib and Radioactive Iodine in Thyroid Cancer Preclinical Model.

Patients with differentiated thyroid cancer (DTC) usually have good prognosis, while those with advanced disease have poor clinical outcomes. This study aimed to investigate the antitumor effects of combination therapy with lenvatinib and 131I (CTLI) using three different types of DTC cell lines with different profiling of sodium iodide symporter (NIS) status. The radioiodine accumulation study revealed a significantly increased radioiodine uptake in K1-NIS cells after lenvatinib treatment, while there was almost no uptake in K1 and FTC-133 cells. However, lenvatinib administration before radioiodine treatment decreased radioiodine uptake of K1-NIS xenograft tumor in the in vivo imaging study. CTLI synergistically inhibited colony formation and DTC cell migration, especially in K1-NIS cells. Finally, 131I treatment followed by lenvatinib administration significantly inhibited tumor growth of the NIS-expressing thyroid cancer xenograft model. These results provide important clinical implications for the combined therapy that lenvatinib should be administered after 131I treatment to maximize the treatment efficacy. Our synergistic treatment effects by CTLI suggested its effectiveness for RAI-avid thyroid cancer, which retains NIS function. This potential combination therapy suggests a powerful and tolerable new therapeutic strategy for advanced thyroid cancer.

CCL4 Functions as a Biomarker of Type 2 Airway Inflammation.

Eosinophilic airway inflammatory disease is associated with bronchial asthma, with eosinophilic chronic rhinosinusitis (ECRS) typical of refractory type 2 airway inflammation. CCL4 produced at local inflammatory sites is involved in them via the accumulation and activation of type 2 inflammatory cells, including eosinophils. The detailed mechanism of CCL4 production remains unclear, and also the possibility it could function as a biomarker of type 2 airway inflammation remains unresolved. In this study, we evaluated CCL4 mRNA expression and production via the TSLP receptor (TSLPR) and toll-like receptors (TLRs) or proteinase-activated receptor-2 (PAR2) in BEAS-2B bronchial epithelial cells co-incubated with purified eosinophils or eosinophil peroxidase (EPX). We examined serum chemokine (CCL4, CCL11, CCL26, and CCL17) and total IgE serum levels, fractionated exhaled nitrogen oxide (FENO), and CCL4 expression in nasal polyps in patients with severe ECRS and asthma. CCL4 was induced by TSLP under eosinophilic inflammation. Furthermore, CCL4 was released via TLR3 signaling, which was enhanced by TSLP. CCL4 was mainly located in nasal polyp epithelial cells, while serum CCL4 levels were reduced after dupilumab treatment. Serum CCL4 levels were positively correlated with FENO, serum IgE, and CCL17 levels. Thus, CCL4 released from epithelial cells via the innate immune system during type 2 airway inflammation may function as a useful biomarker for the condition.

Effect of decreased tongue pressure on dysphagia and survival rate in elderly people requiring long-term care.

Background/purpose: Tongue pressure plays an important role in swallowing function. The purpose of this study is to investigate whether decreased tongue pressure is associated with dysphagia and the development of pneumonia in the elderly requiring long-term care. Materials and methods: Tongue pressure measurement and swallowing videoendoscopic (VE) examination were performed in 60 hospitalized elderly people (33 males and 27 females, with an average age of 84.3 years) to investigate the relationship with the clinical course. Factors related with dysphagia was analyzed by Fisher's exact test and one-way ANOVA, followed by multivariate logistic regression. The relationship between each variable and survival were analyzed by cox regression. Results: Twenty-one patients had dysphagia by VE examination. Multivariate analysis showed that smaller BMI and reduced tongue pressure were significantly correlated with dysphagia. Smaller number of remaining teeth and dysphagia were significantly related to pneumonia-related death. No patients with tongue pressure of larger than 20 kpa died by pneumonia within one year, while in those with tongue pressure of smaller than 20 kpa, one-year cumulative survival rate by pneumonia was 44.3%. Conclusion: Decreased tongue pressure was significantly associated with dysphagia and may increase the risk of pneumonia-related death in the elderly requiring long-term care.

Useful diagnostic histogenetic features of ectopic odontogenic ghost cell tumours.

BACKGROUND: Ectopic odontogenic tumours are rare and difficult to diagnose. Consequently, they are occasionally misdiagnosed as other tumours and overtreated. Dentinogenic ghost cell tumours (DGCTs) are odontogenic neoplasms characterised by a CTNNB1 mutation, ghost cell appearance, and dentinoid-like calcification. Herein, we present a case of ectopic DGCT on the floor of a patient's mouth, providing reliable clinicopathological and genetic evidence of its odontogenicity for the first time. CASE PRESENTATION: A 72-year-old man presented with painless sublingual swelling. Imaging revealed a multi-lobulated, solid-cystic mass on the floor of his mouth. Cytological evaluation showed folded epithelial clusters composed of basaloid cells, keratinised material, and calcification. Histological analysis revealed a multi-cystic, cribriform to solid nest, with an odontogenic satellate reticulum-like epithelium, including ghost cells and dentinoid matrix deposition. Immunohistochemical analysis found that CK19, CK5/6, bcl-2, and p63 were diffuse positive, ß-catenin was focal positive in the nuclei, and the cells in the dentinoid matrix were positive for DMP1. The CTNTTB1 mutation was detected, leading to the final diagnosis of ectopic DGCT. There was no recurrence during the 6-month follow-up. CONCLUSIONS: Overall, we have presented a comprehensive clinical overview of DGCT and identified its pathological and genetic features. This report will aid in the recognition of this rare disease in the future and help to avoid misdiagnosis and overtreatment.