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KAKEI YasumasaUniversity Hospital / Center for Clinical ResearchAssociate Professor
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■ Paper- OBJECTIVE: To evaluate the long-term hearing outcomes of infants with symptomatic congenital cytomegalovirus (CMV) disease who received 16 mg/kg of oral valganciclovir (VGCV) twice daily for six months. STUDY DESIGN: We have currently performed a long-term extension study of an investigator-initiated, single-arm, prospective, multicenter clinical trial, in which 24 infants were treated with VGCV. Hearing outcomes up to three years after treatment initiation were described and the longitudinal changes in the proportion of "Improved hearing" were analyzed using logistic regression. The factors associated with these outcomes were explored. Adverse events that occurred after the completion of the administration period were assessed. RESULTS: At 3 years, among 48 ears from 24 infants, the number of "improved hearing," which was 19 (40.0 %) ears at 6 months, increased to 27 (56.3 %) ears (p = 0.032). When including "maintaining normal hearing" or "maintaining normal hearing or the same degree of hearing impairment", the corresponding numbers were observed in 35 (72.9 %) and 45 (93.7 %) ears at 3 years, which were 25 (52.5 %) and 45 (93.7 %) ears at 6 months, respectively. Infants with milder hearing impairment at baseline showed high likelihood of hearing improvement (p for trend = 0.018 by the regression analysis). No adverse events were observed after completion of the administration period. CONCLUSION: Oral administration of VGCV demonstrated efficacy in improving hearing in infants with symptomatic congenital CMV disease at 3 years of age. These results suggest that the treatment response may be particularly favorable in patients with a lower initial degree of hearing impairment.Lead, Mar. 2025, Journal of clinical virology : the official publication of the Pan American Society for Clinical Virology, 177, 105778 - 105778, English, International magazine[Refereed]Scientific journal
- BACKGROUND: This is a multicenter, open-label, single-arm clinical trial to evaluate the safety and efficacy of oral cancer vaccine B440 in patients with PD-1/PD-L1 inhibitor-resistant advanced urothelial cancer. METHODS: The trial will be performed at three university hospitals in Japan. The target number of patients will be 12. The patients will be treated orally with B440 once daily for 5 days followed by 2 days for four consecutive courses (4 weeks, 20 treatments). The low-dose group will receive 800 mg (4 capsules) per dose and the high-dose group will receive 1,600 mg (8 capsules) per dose. The primary outcome will be the number and incidence of DLT cases the start of treatment and Day 28. Secondary outcomes are the presence or absence of a response, the best overall response and PFS. DISCUSSION: If this trial shows B440 to be safe and effective, it may lead to a late phase randomized controlled trial in advanced urothelial cancer. Ultimately, we hope to provide a new treatment option for such patients. TRIAL REGISTRATION: Japan Registry of Clinical Trials (jRCT) identifier: jRCT2051220143. Registered on December 27, 2022.Corresponding, Feb. 2025, BMC cancer, 25(1) (1), 195 - 195, English, International magazine[Refereed]Scientific journal
- Jan. 2025, Journal of Clinical Medicine[Refereed]Scientific journal
- OBJECTIVE: To evaluate the effect and safety of sclerotherapy in patients with difficult-to-resect venous malformations treated with ethanolamine oleate. DESIGN AND SETTING: This investigator-initiated clinical trial employed a multicenter, single-arm design and was conducted in Japan. PATIENTS: Overall, 44 patients with difficult-to-resect venous malformations were categorized into two cohorts: 22 patients with cystic-type malformations and 22 patients with diffuse-type malformations, including children (<15 years old). INTERVENTIONS: Adult patients received injections of 5% ethanolamine oleate solution, double diluted with contrast or normal saline, with a maximum dose of 0.4 mL/kg. The same method of administration was used for children (<15 years old). The maximum volume of the prepared solution in one treatment was 30 mL. EVALUATION METHODS: Treatment effect was assessed by evaluating the difference in lesion volume using magnetic resonance imaging as a primary endpoint and differences in pain using a visual analog scale as a key secondary endpoint. RESULTS: Among the 45 patients who consented, one was excluded owing to potential intracranial involvement of venous malformations during screening. Regarding the primary outcome, 26 of 44 patients (59.1%, 95% confidence interval: 44.41-72.31%) achieved ≥ 20% reduction in malformation volume, with 16 patients having cystic lesions (72.7%, 51.85-86.85%) and 10 patients having diffuse lesions (45.5%, 26.92-65.34%). Both cohorts showed significant improvement in self-reported pain scores associated with lesions 3 months post-sclerotherapy. No death or serious adverse events occurred. Hemoglobinuria was observed in 23 patients (52%), a known drug-related adverse event. Prompt initiation of haptoglobin therapy led to full recovery within a month for these patients. CONCLUSIONS: Ethanolamine oleate shows potential as a therapeutic sclerosing agent for patients with difficult-to-resect venous malformations.2025, PloS one, 20(1) (1), e0303130, English, International magazine[Refereed]Scientific journal
- OBJECTIVES: The effects of systemic inflammation on the temporomandibular joint (TMJ) are poorly understood. This study aimed to establish a mouse model to study the effects of systemic inflammation on the TMJ. MATERIALS AND METHODS: SKG mice, a BALB/c strain with spontaneous onset of rheumatoid arthritis-like symptoms due to a spontaneous point mutation (W163C) in the gene encoding the SH2 domain of ZAP-70, were treated with zymosan (β-1,3-glucan). Synovitis, bone erosion, and cartilage damage in the TMJ were evaluated using established scores for animal models of inflammatory arthritis. Myeloperoxidase-positive areas and numbers of tartrate-resistant acid phosphatase (TRAP)-positive cells were compared between naive and zymosan-treated SKG mice. Correlations between TMJ inflammation scores and clinical scores for extremities were also assessed. RESULTS: There were significant differences in TMJ inflammation scores, including synovitis, bone erosion, and cartilage damage, between naive and high-dose zymosan-treated mice. There were significant differences in myeloperoxidase-positive areas and numbers of TRAP-positive cells between naive and zymosan-treated mice. There were significant correlations between TMJ inflammation scores and clinical scores for extremities. CONCLUSIONS: Systemic administration of zymosan efficiently induces TMJ inflammation in SKG mice. Zymosan-treated SKG mice offer a useful tool to investigate the effects of systemic inflammation on the TMJ.Dec. 2024, Oral diseases, English, International magazine[Refereed]Scientific journal
- Lead, Oct. 2024, Journal of Infection and Chemotherapy[Refereed]Scientific journal
- Aug. 2024, Contemporary Clinical Trials Communications[Refereed]Scientific journal
- PurposeThis retrospective study aimed to investigate the effect of frequent computed tomography (CT) examinations with contrast media on the renal function of patients with oral squamous cell cancer (OSCC) that underwent radical surgery, by using estimated glomerular filtration rate (eGFR); to identify risk factors of occurrence of post-operative chronic kidney disease (CKD) in these patients; and to explore the relationship between risk factors and occurrence of postoperative CKD during follow-up.MethodsHerein, 188 patients (107 male; 81 female) who underwent radical surgery for OSCC were included. We evaluated the risk factors for postoperative CKD after treatment, including demographic, perioperative, and postoperative factors by univariate and multivariate analyses. Patients were divided into post-operative CKD and control groups based on eGFR evaluation. Overall survival (OS) rates were compared between the groups.ResultseGFR decreased over time after treatment in both patient groups. Postoperative CKD was diagnosed in 56 (29.8%) patients. The average number of contrast-enhanced CT examinations was not an independent risk factor for postoperative CKD. However, lower hemoglobin on hospital discharge [odds ratio (OR) = 0.53], lower eGFR on hospital discharge (OR = 0.84), and common use of nonsteroidal anti-inflammatory drugs (OR = 48.79) were significant risk factors associated with postoperative CKD. The control group was associated with a better OS than the postoperative CKD group; however, this difference was not significant.ConclusionsClinicians should pay close attention to these risk factor of post-operative CKD during the management of patients with OSCC that undergo radical surgery and frequent follow-up CT examinations with contrast media.SPRINGER INDIA, Aug. 2024, Journal of maxillofacial and oral surgery, 23(4) (4), 824 - 830, English, International magazine[Refereed]Scientific journal
- Congenital cytomegalovirus (cCMV) infection is the most common congenital infection in developed countries. Although a standard therapy has not yet been established, evidence for the management of cCMV infection has been accumulating. The first edition of the "Clinical Practice Guidelines for the Management of Congenital Cytomegalovirus Infection" was published in Japan in 2023. This summary outlines the clinical questions (CQs) in the guidelines, with reference to the Japanese Medical Information Distribution Service Manual. Overall, 20 CQs with statements regarding prenatal risk assessment, prevention and management at diagnosis (CQs 1-1-1-3), diagnosis (CQs 2-1-2-6), treatment (CQs 3-1-3-7) and follow-up requirements (CQs 4-1-4-4) have been discussed. For each statement, the levels of recommendation, evidence and consensus rates were determined. These guidelines will assist in the management of patients with cCMV infection.Jul. 2024, The Pediatric infectious disease journal, English, International magazine[Refereed]Scientific journal
- Patients undergoing palliative care often develop debilitating oral conditions, including xerostomia. These conditions may significantly impact patients' quality of life. Despite the high prevalence and adverse impact of xerostomia, effective management strategies remain unclear. This scoping review was performed to elucidate effective interventions for xerostomia in patients undergoing palliative and end-of-life care. A comprehensive search strategy was employed to identify relevant studies up to August 2023. Full-text primary articles focusing on xerostomia in patients receiving palliative care were included in the review. Eleven articles were selected for analysis, and data were extracted by six reviewers. This review followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Among the 11 studies, interventions ranged from oral care to saliva substitutes and methods to stimulate saliva secretion. The primary method of assessing xerostomia was the performance of subjective evaluations using visual analog scale scores or numerical rating scale scores. Various interventions including oral care regimens, topical treatments, and mixed efficacy outcomes were reported. Notably, only one study directly measured the saliva volume, highlighting a reliance on subjective endpoints in most studies. Although no definitive conclusions can be drawn regarding the most effective intervention, oral care was a preferred option for managing xerostomia in patients undergoing palliative care. Additionally, adjunctive treatments such as ice cubes, saline, and moisturizers showed promise but require further investigation. Objective measures should be incorporated into future intervention trials to complement subjective assessments and provide a comprehensive evaluation of xerostomia management strategies in this patient population.Jun. 2024, Cureus, 16(6) (6), e63002, English, International magazine[Refereed]Scientific journal
- AIMS/INTRODUCTION: Insulin resistance syndrome and lipoatrophic diabetes are rare conditions characterized by the development of treatment-refractory diabetes with severe insulin resistance. We recently conducted a 24 week, multicenter, single-arm trial (EMPIRE-01) that demonstrated a certain level of effectiveness and safety of empagliflozin for these conditions. To evaluate treatment safety over a longer period, we have now performed an additional 28 week trial (EMPIRE-02) that followed on from EMPIRE-01. MATERIALS AND METHODS: The primary and secondary outcomes were safety and efficacy evaluations, respectively. All eight subjects of the EMPIRE-01 trial participated in EMPIRE-02. RESULTS: Twenty adverse events (AEs) were recorded among five individuals during the combined 52 week treatment period of both trials. Whereas one case of chronic hepatitis B was moderate in severity, all other AEs were mild. There were thus no serious AEs or events necessitating discontinuation or suspension of treatment or a reduction in drug dose. Whereas ketoacidosis or marked increases in serum ketone body levels were not observed, the mean body mass of the subjects was decreased slightly after completion of EMPIRE-02. The improvement in mean values of glycemic parameters observed in EMPIRE-01 was not sustained in EMPIRE-02, mostly because of one individual whose parameters deteriorated markedly, likely as a result of nonadherence to diet therapy. The improvement in glycemic parameters was sustained during EMPIRE-02 after exclusion of this subject from analysis. CONCLUSIONS: Empagliflozin demonstrated a certain level of safety and efficacy for the treatment of insulin resistance syndrome and lipoatrophic diabetes over 52 weeks, confirming its potential as a therapeutic option.May 2024, Journal of diabetes investigation, English, Domestic magazine[Refereed]Scientific journal
- Introduction In our previous work, we investigated the analgesic effects of ibuprofen gargle after mandibular third molar extractions. However, a subsequent detailed review of individual patient data revealed variations in postoperative pain reduction among patients. Consequently, the present study was designed to conduct post-hoc subanalyses that identified factors contributing to variation in the analgesic response to ibuprofen gargle after third molar extractions. Materials and methods This study involved thirty-five Japanese patients from a prior randomized, double-blind, placebo-controlled, crossover study, which focused on the analgesic effects of ibuprofen gargle after mandibular third molar extractions. Participants were categorized as responders (n = 13) and non-responders (n = 22) based on the within-subject difference (ibuprofen-placebo, IP) of visual analog scale (VAS) changes. Baseline characteristics were compared, along with variables, such as age, sex, the reason for extraction, extraction site, Pell Gregory (space and depth) classification, Winter's classification, surgeon's experience, and surgery time. Baseline characteristics predicting responder status were examined using multivariate logistic regression. Results In the univariate analysis, variables such as age, sex, and baseline VAS scores with p-values <0.2 were evaluated using a stepwise approach. This analysis identified age (per -10 years) with an odds ratio of 4.163 (95% confidence interval (CI): 1.170-31.952, p = 0.0233) and sex (female) with an odds ratio of 9.977 (95% CI: 1.336-208.256, p = 0.0213) as significant predictors of responder status. Conclusions In young and female patients, ibuprofen gargle decreased postoperative pain after mandibular third molar extractions.Apr. 2024, Cureus, 16(4) (4), e57516, English, International magazine[Refereed]Scientific journal
- INTRODUCTION: Insulin resistance syndrome and lipoatrophic diabetes are characterized by severe insulin resistance and are often refractory to treatment. Trials assessing the efficacy of antidiabetes drugs for these rare conditions have been limited, however. Sodium-glucose cotransporter 2 (SGLT2) inhibitors, which lower glycemia independently of insulin action, have shown efficacy for type 2 diabetes with insulin resistance. We here investigated the efficacy and safety of the SGLT2 inhibitor empagliflozin for treatment of insulin resistance syndrome and lipoatrophic diabetes. METHODS: The trial was conducted at five academic centers in Japan and included seven patients with insulin resistance syndrome and one patient with lipoatrophic diabetes. Participants received 10 mg of empagliflozin daily. If the hemoglobin A1c (HbA1c) level was ≥ 7.0% (52 mmol/mol) after 12 weeks, the dose was adjusted to 25 mg. The study duration was 24 weeks, and the primary outcome was the change in HbA1c level by the end of the treatment period. Safety evaluations were performed for all participants. RESULTS: By the end of the 24-week treatment period, the mean HbA1c level for all eight patients had decreased by 0.99 percentage points (10.8 mmol/mol) (95% confidence interval [CI], 0.59 to 1.38 percentage points, 6.6 to 14.9 mmol/mol) and the mean fasting plasma glucose concentration had declined by 63.9 mg/dL (3.55 mmol/L) (95% CI 25.5 to 102.3 mg/dL, 1.42 to 5.68 mmol/L). Continuous glucose monitoring revealed a reduction in mean glucose levels from 164.3 ± 76.1 to 137.6 ± 46.6 mg/dL (9.13 ± 4.23 to 7.65 ± 2.59 mmol/L) as well as an increase in the time in range (70-180 mg/dL) from 58.9 ± 36.1% to 70.8 ± 18.3%. Seventeen mild adverse events were recorded in five individuals throughout the study period. No severe events were reported. The mean body mass showed a slight decrease and the mean serum ketone body concentration showed a slight increase during treatment. CONCLUSION: Our results demonstrate that empagliflozin shows a certain level of efficacy and safety for treatment of insulin resistance syndrome and lipoatrophic diabetes. TRIAL REGISTRATION: jRCTs2051190029 and NCT04018365.Jan. 2024, Diabetes therapy : research, treatment and education of diabetes and related disorders, English, International magazine[Refereed]Scientific journal
- BACKGROUND: For treating patients with refractory chronic spontaneous urticaria (CSU) resistant to standard doses of 2nd generation H1-antihistamines (H1AH) the International and Japanese guidelines recommend increasing H1AH dose. The latter also recommends switching to a different H1AH. This study explored if the efficacy of the standard dose of bilastine 20 mg is non-inferior to that of double-dose of H1AH in patients with refractory CSU. METHODS: This phase IV, multicenter, open-label, randomized, parallel-group trial evaluated the efficacy and safety of switching treatment to bilastine compared to treatment with a 2-fold dose of H1AH in patients with CSU refractory to standard dose H1AH. The primary endpoint was the mean total symptom score (TSS) at Day 5-7 after the start of administration. RESULTS: Treatment efficacy and safety were evaluated in 128 patients (bilastine, n=64; 2-fold dose of H1AH, n=64). The mean TSS at Day 5-7 after the start of administration was smaller than the non-inferiority margin of 0.8, demonstrating non-inferiority of the bilastine switching group to the double-dose H1AH group (0.17 (95% CI -0.32, 0.67)). No difference in Japanese version of Epworth Sleepiness Scale (JESS), DLQI, and urticaria activity score over 7 consecutive days (UAS7) was observed between the two groups. There were no serious adverse events in either group. H1AH-related adverse events occurred in 5 subjects (8 cases) and 2 subjects (3 cases) in the double-dose H1AH and bilastine groups, respectively. CONCLUSIONS: Switching treatment to bilastine demonstrated non-inferiority to a double-dose of H1AH in terms of efficacy in patients with CSU refractory to standard dose H1AH with a favorable safety profile. CLINICAL TRIAL REGISTRATION: https://jrct.niph.go.jp/latest-detail/jRCTs051180105, identifier jRCTs051180105.2024, Frontiers in immunology, 15, 1441478 - 1441478, English, International magazine[Refereed]Scientific journal
- INTRODUCTION: Head and neck squamous cell carcinoma (HNSCC) treatment includes surgery, radiotherapy, and immunotherapy with the aim of eradicating cancer cells without affecting normal tissues. HNSCC expresses epidermal growth factor receptor (EGFR) and cetuximab, an IgG1 monoclonal antibody targeting epidermal growth factor receptor, has been approved for the treatment of HNSCC. However, cetuximab has low reactivity and induces serious side effects. Gold nanoparticles (AuNPs) were reported to enhance the local antitumor effects of radiotherapy without damaging normal cells. METHODS AND RESULTS: This study investigated the in vitro effects of single and combination therapy with AuNPs (1.0 nM), cetuximab (30 nM), and radiotherapy (4 Gy) on a human HNSCC cell line, HSC-3. Combination treatment of AuNPs + cetuximab + radiotherapy markedly reduced HSC-3 numbers and proliferation and enhanced apoptosis compared with single and double combination treatments. Furthermore, the in vivo combination treatment (AuNPs + cetuximab + radiotherapy) of a xenograft model of HSC-3 cells transplanted into nude mice (BALB/cAJcl-nu/nu) reduced the tumor volume compared with the controls. Scanning electron microscopy demonstrated the presence of AuNPs in tumor tissues and toxicity analysis indicated that AuNPs had no toxic effect on normal tissues. CONCLUSIONS: This study showed that AuNPs alone do not have a tumor-suppressing effect, but they sensitize tumors to radiotherapy and bind to cetuximab, leading to enhanced antitumor effects.Corresponding, Dec. 2023, Cancers, 15(23) (23), English, International magazine[Refereed]Scientific journal
- Dec. 2023, Cureus, English[Refereed]Scientific journal
- OBJECTIVE: This study was designed to evaluate the postoperative efficacy and safety of using an ibuprofen gargle as a pain management strategy for patients who have undergone mandibular third molar extraction. We also ensured that the quality of treatment was not compromised throughout the study. MATERIAL AND METHODS: Patients were randomized in a 1:1 ratio into two groups: the ibuprofen-placebo (IP) group and the placebo-ibuprofen (PI) group. On postoperative Day (POD) 1, the IP group initiated ibuprofen administration, while the PI group started taking placebo. On POD 2, the IP group switched to using placebo, whereas the PI group switched to ibuprofen. From PODs 3-5, both groups were prescribed ibuprofen gargle. The primary endpoint was within-subject visual analog scale (VAS) score before and 5 min after the first use of the ibuprofen or placebo gargle on PODs 1 and 2 (ΔVAS5_ibuprofen - ΔVAS5_placebo ). The incidence and severity of adverse events were assessed using the Common Terminology Criteria for Adverse Events version 5.0 and a subjective rating scale. RESULTS: This study enrolled 40 patients. The within-subject VAS5 of the IP and PI groups were 1.25 ± 12.0 and -5.26 ± 8.93 mm, respectively. The treatment effect of ibuprofen gargle was -2.01 ± 10.62 mm (p = .246). None of the patients in each group presented with serious adverse events or clinically significant complications (including dry sockets) after extraction. Transient adverse events, such as throat tingling and oral discomfort (grade 1), were observed in each group. CONCLUSION: Ibuprofen gargle was safe but did not provide significant pain relief when used after mandibular third molar extraction.Nov. 2023, Clinical and experimental dental research, English, International magazine[Refereed]Scientific journal
- BACKGROUND: Head and neck cancers that cause severe aesthetic and functional disorders normally metastasize to the cervical lymph nodes. Patients with cervical lymph node metastasis are undergoing neck dissection. Shoulder complaints are common after neck dissection, with patients reporting symptoms such as pain, weakness, shoulder droop, and disability. However, no safe and effective treatment is available for this condition at present. We will conduct a double-blinded, randomized controlled trial to evaluate the efficacy of carbon dioxide (CO2) paste in relieving pain in patients after neck dissection. OBJECTIVE: This will be the first clinical study to compare the efficacy of CO2 paste with placebo in relieving postoperative pain in patients who underwent neck dissection. METHODS: We will perform this trial at the Kobe University Hospital in Japan. Patients will be randomized 1:1 into the CO2 paste and control groups. Patients in the CO2 paste group will have the CO2 paste applied to the cervical surface skin for 10 minutes once per day for 14 consecutive days. The primary end point of the study is a change in the visual analog scale (VAS) scores of neck pain from baseline on day 1 (preapplication) to the end of drug application (day 15). Secondary end points include changes in the following parameters from baseline on day 1 to the end of drug application (day 15) or the study (day 29): neck pain VAS score (days 1-29), grip strength (days 1-15 and 1-29), VAS scores for subjective symptoms (the feeling of strangulation, numbness, swelling, and warmth in the neck and shoulder region) for days 1-15 and 1-29, whether the VAS score improved more than 30% (days 1-15), the arm abduction test (days 1-15 and 1-29), shoulder range of motion (abduction and flexion) for days 1-15 and 1-29, occurrence of skin disorders, and occurrence of serious side effects. Periodic monitoring will be conducted for participants during the trial. This study was approved by the certified review board of Kobe University. RESULTS: The intervention commenced in May 2021 and will continue until March 2024. The collected data will provide information on the efficacy of the CO2 paste treatment. The primary end point will be compared using the Wilcoxon test, with the 1-sided significance level set at 5%. Each evaluation item will be summarized. Secondary efficacy end points will be analyzed to provide additional insights into the primary analysis. Findings based on the treatment effects are expected to be submitted for publication in 2025. CONCLUSIONS: This trial will provide exploratory evidence of the efficacy and safety of CO2 paste in relieving pain in patients after neck dissection. TRIAL REGISTRATION: Japan Registry of Clinical Trials (jRCT) identifier: jRCTs051210028; https://jrct.niph.go.jp/en-latest-detail/jRCTs051210028. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/50500.Nov. 2023, JMIR research protocols, 12, e50500, English, International magazine[Refereed]Scientific journal
- OBJECTIVE: Although benign, ameloblastoma is a locally aggressive lesion in some patients and the development of additional treatments is needed. Verteporfin (VP) is a photosensitizer exhibiting considerable photocytotoxicity in various tumor cells. We aimed to investigate the effects of verteporfin photodynamic therapy (VP PDT) on ameloblastoma. METHODS: Eighteen patients who underwent surgery for ameloblastoma were randomly selected. We performed an immunohistochemical assessment to investigate the expression of low-density lipoprotein receptor (LDLR) and Yes-associated protein (YAP), targets of VP, in human ameloblastoma tissues and cultured human ameloblastoma cell line (HAM1). The effect of VP PDT on cell proliferation and apoptosis in HAM1 was analyzed. RESULTS: The expression of LDLR and YAP were detected in human ameloblastoma tissues and HAM1. LDLR expression was significantly higher in patients who had previously undergone surgery than in patients who were receiving it for the first time. The cytotoxic effect of the combination of low-concentration VP administration and laser irradiation was comparable to high-concentration VP administration with and without laser irradiation. The addition of laser irradiation to VP administration significantly accelerated apoptotic bleb formation compared with VP administration alone. CONCLUSION: VP PDT has the potential to become an additional treatment for large-sized ameloblastoma.Oct. 2023, Oral diseases, English, International magazine[Refereed]Scientific journal
- Mitochondrial dysfunction and respiratory function changes have been consistently associated with the initiation and progression of cancer. The purpose of this study was to retrospectively investigate the expression of mitochondrial tumor-suppressor and DNA-repair proteins in patients with oral squamous cell carcinoma (OSCC) and to evaluate the relationship between their expression and prognosis. We enrolled 197 patients with OSCC who underwent surgical resection between August 2013 and October 2018. Clinical, pathological, and epidemiological data were retrospectively collected from hospital records. The expression of peroxisome proliferator-activated receptor gamma coactivator-1α (PGC-1α), mitochondrial transcription factor A, mitochondrial tumor suppressor gene 1, silent information regulator 3, and 8-hydroxyguanine DNA glycosylase was investigated using immunochemistry. The 3-year disease-specific survival (DSS) rates of patients showing positive expression of all selected proteins were significantly higher than those of patients showing a lack of expression. Multivariate analysis revealed that the expression of PGC-1α (hazard ratio, 4.684) and vascular invasion (hazard ratio, 5.690) can predict the DSS rate (p < 0.001). Low PGC-1α expression and vascular invasion are potential clinically effective predictors of the prognosis of OSCC.Aug. 2023, Cancers, 15(16) (16), English, International magazine[Refereed]Scientific journal
- Although perineurium has an important role in maintenance of the blood-nerve barrier, understanding of perineurial cell-cell junctions is insufficient. The aim of this study was to analyze the expression of junctional cadherin 5 associated (JCAD) and epidermal growth factor receptor (EGFR) in the perineurium of the human inferior alveolar nerve (IAN) and investigate their roles in perineurial cell-cell junctions using cultured human perineurial cells (HPNCs). In human IAN, JCAD was strongly expressed in endoneurial microvessels. JCAD and EGFR were expressed at various intensities in the perineurium. In HPNCs, JCAD was clearly expressed at cell-cell junctions. EGFR inhibitor AG1478 treatment changed cell morphology and the ratio of JCAD-positive cell-cell contacts of HPNCs. Therefore, JCAD and EGFR may have a role in the regulation of perineurial cell-cell junctions.Jun. 2023, The journal of histochemistry and cytochemistry : official journal of the Histochemistry Society, 71(6) (6), 221554231182193 - 221554231182193, English, International magazine[Refereed]Scientific journal
- Implant-supported removable prostheses (ISrP) improve the quality of life, especially in patients who underwent mandibular reconstruction, but few studies have focused on the effect of ISrP in the fibular mandible on the function of the temporomandibular joint. The purpose of this pilot case series was to determine the usefulness of four-dimensional computed tomography (4DCT) images for the evaluation of differences in condylar movements with and without ISrP. Three patients who underwent ISrP following segmental mandibulectomy and free-flap reconstruction were evaluated. The participants were instructed to masticate a cookie during the 4DCT scan. The distance between the most anterior and posterior positions of the condyles on the sagittal view of the 4DCT images during the chewing of the cookies was measured and compared with and without ISrP. 4DCT revealed changes in the distances of condylar protrusion with and without wearing ISrP, but there were no obvious differences among the three patients. The 4DCT motion analysis was useful for the evaluation of the effect of wearing ISrP on condylar movements during mastication in patients with mandibular reconstruction and may become a useful objective evaluation method for the functional evaluation of ISrP.May 2023, Cureus, 15(5) (5), e39419, English, International magazine[Refereed]
- BACKGROUND: The purpose of this retrospective study was to investigate the prognosis of patients with oral cavity cancer with positive margin (PM) or close margin (CM) divided into pN- and pN+ groups. METHODS: The evaluated endpoints were local control and disease-specific survival (DSS) rates. RESULTS: Higher T classification, lymphovascular space invasion (LVSI), and older age were significant risk factors for DSS in the pN- groups. On the other hand, extranodal extension, multiple lymph node metastases, and LVSI were significant risk factors for DSS in the pN+ groups. Among the CM pN+ patients, no significant differences in the 3-year DSS were observed between the only surgery (51.9%) and adjuvant groups (53.2%). CONCLUSIONS: Higher T classification and LVSI are high-risk features more than PM or CM in the pN- groups for DSS. However, further prospective studies are needed to demonstrate the usefulness of adjuvant treatment in patients with PM or CM.Mar. 2023, Head & neck, 45(6) (6), 1418 - 1429, English, International magazine[Refereed]Scientific journal
- INTRODUCTION: This is a multicentre, open-label, single-arm clinical trial to evaluate the efficacy and safety of apalutamide in patients with metastatic castration-resistant prostate cancer. METHODS AND ANALYSIS: The trial will be performed at 4 university hospitals and 14 city hospitals in Japan. The target number of patients will be 110. The patients will be orally administered 240 mg apalutamide once daily during the treatment period. The primary outcome is the prostate-specific antigen (PSA) response rate. PSA response is defined as ≥50% decline from baseline at 12 weeks. Secondary outcomes are time to PSA progression, progression-free survival, overall survival, progression-free survival during second therapy, ≥50% decline in PSA from baseline at 24 and 48 weeks, ≥90% decline in PSA from baseline or lower PSA detection sensitivity after the initial dose at 12, 24 and 48 weeks, PSA maximal changes, accumulated PSA response from screening to 24 and 48 weeks, and grade 3 or 4 adverse events according to the Common Terminology Criteria for Adverse Events version 4.0. ETHICS AND DISSEMINATION: This study has been approved by the Certified Research Review Board of Kobe University (No. CRB5180009). All participants will be required to provide written informed consent. Findings will be disseminated through scientific and professional conferences and peer-reviewed journal publications. The datasets generated during the study will be available from the corresponding author on reasonable request. TRIAL REGISTRATION NUMBER: jRCTs051220077.Corresponding, Mar. 2023, BMJ Open, 13(3) (3), e070173, English, International magazine[Refereed]Scientific journal
- INTRODUCTION: Xeroderma pigmentosum (XP) is a rare intractable disease without a fundamental treatment, presenting with severe photosensitivity, freckle-like pigmented and depigmented maculae and numerous skin cancers before the age of 10 years without strict sun protection. About 70% of the patients exhibit extremely severe sunburn reactions and most of them develop neurological symptoms, including sensorineural hearing impairment and progressive peripheral and central nervous disorders beginning from childhood ages. In the preclinical study, we found that N-acetyl-5-methoxytryptamine was effective in suppressing skin tumour development in addition to improvement of auditory brainstem response in chronically ultraviolet-irradiated XP-A model mice. METHODS AND ANALYSIS: On the bases of the preclinical study, we conduct a clinical trial on the efficacy of NPC-15 for patients with XP with exaggerated sunburn reaction type by a multicentre, double-blinded placebo-controlled, two-group crossover study followed by a 52 weeks open study. ETHICS AND DISSEMINATION: Ethics approval is overseen by the Kobe University Institutional Review Board and Osaka Medical and Pharmaceutical University Institutional Review Board, and the study is conducted in accordance with the approved protocol. All participants will be required to provide written informed consent. Findings will be disseminated through scientific and professional conferences and peer-reviewed journal publications. The data sets generated during the study will be available from the corresponding author on reasonable request. TRIAL REGISTRATION NUMBER: jRCTs051210181.Corresponding, Mar. 2023, BMJ Open, 13(3) (3), e068112, English, International magazine[Refereed]Scientific journal
- BACKGROUND: Congenital cytomegalovirus (CMV) infection (cCMV) can cause sensorineural hearing loss and neurodevelopmental disabilities in children. Oral valganciclovir (VGCV) therapy has been reported to improve long-term audiological and neurodevelopmental outcomes in patients with cCMV. The levels of CMV DNA in whole blood have been monitored in previous studies. However, quantitative methods using whole blood have not been standardized. Recently, the plasma viral load has been standardized and widely used in CMV-associated diseases. METHODS: CMV viral loads in whole blood and plasma were serially measured in 24 patients with a confirmatory diagnosis of cCMV during oral VGCV therapy using an in-house real-time PCR assay. Plasma samples were assayed using the Cobas 6800 system (Roche Diagnostics) in addition to an in-house assay. RESULTS: Plasma CMV viral loads were remarkably decreased at the end of therapy compared to before therapy. A significant correlation of CMV levels between whole blood and plasma was observed (Spearman's ρ = 0.566). The levels of CMV DNA before therapy were significantly correlated with the period of decreasing the viral loads to below the detection limit, not only in whole blood (Spearman's ρ = 0.901) but also in plasma (Spearman, ρ = 0.804). Finally, CMV viral loads between the in-house assay and commercially available standardized assay in 75 plasma samples with positive PCR results for CMV were compared; a significant correlation was observed between the results of both assays. CONCLUSIONS: There was a significant correlation between the two assays (Spearman, ρ = 0.882), suggesting that CMV plasma viral loads measured by the standardized assay are widely used to monitor the levels of CMV DNA in patients with cCMV during oral VGCV therapy.Jan. 2023, BMC infectious diseases, 23(1) (1), 31 - 31, English, International magazine[Refereed]Scientific journal
- Oral lichen planus (OLP) is a type of chronic and refractory stomatitis characterized by abnormal keratinization, which is often painful. There is no consensus regarding treatment options for OLP, particularly in the presence of pain. The current study protocol focuses on the short-term efficacy and long-term safety of an ibuprofen gargle for pain management in patients with OLP. Patients (n = 24) with painful OLP will be enrolled. During a crossover study period, patients in the ibuprofen–placebo (IP) group will receive an ibuprofen gargle (0.6%) on day 1, a placebo gargle on day 2, and an ibuprofen gargle on days 3–5 at least once daily. Patients in the placebo–ibuprofen (PI) group will receive a placebo gargle on day 1, an ibuprofen gargle on day 2, and an ibuprofen gargle on days 3–5 at least once daily. The primary endpoint of the crossover study period is the change in pain level as measured by a visual analogue scale score from before gargle administration to 5 min after gargle administration on days 1 and 2. The primary endpoint of the long-term extension study is assessment of long-term safety. The results of this study may support existing evidence regarding the effectiveness of ibuprofen rinses in treating OLP.Corresponding, MDPI AG, Jan. 2023, Methods and Protocols, 6(1) (1), 7 - 7[Refereed]Scientific journal
- Oral squamous cell carcinoma (OSCC) is the most common head and neck cancer. Cancer-associated fibroblasts (CAFs) are the main stromal cells in the tumor microenvironment (TME). As CAFs promote tumor progression and hypoxia in the TME, regulating the conversion of normal fibroblasts (NFs) into CAFs is essential for improving the prognosis of patients with OSCC. We have previously reported the antitumor effects of transcutaneous carbon dioxide (CO2) application in OSCC. However, the effects of reducing hypoxia in the TME remain unclear. In this study, we investigated whether CO2 administration improves the TME by evaluating CAFs marker expression. Human OSCC cells (HSC-3) and normal human dermal fibroblasts (NHDF) were coinjected subcutaneously into the dorsal region of mice. CO2 gas was applied twice a week for 3 weeks. The tumors were harvested six times after transcutaneous CO2 application. The expression of CAFs markers (α-SMA, FAP, PDPN, and TGF-β) were evaluated by using real-time polymerase chain reaction and immunohistochemical staining. The expression of α-SMA, FAP, PDPN, and TGF-β was significantly increased over time after co-injection. In the CO2-treated group, tumor growth was significantly suppressed after treatment initiation. In addition, the mRNA expression of these markers was significantly inhibited. Furthermore, immunohistochemical staining revealed a significant decrease in the protein expression of all CAFs markers in the CO2-treated group. We confirmed that transcutaneous CO2 application suppressed CAFs marker expression and tumor growth in OSCC xenograft mouse model.2023, PloS one, 18(8) (8), e0290357, English, International magazine[Refereed]Scientific journal
- BACKGROUND: This study investigated how cognitive function-related simple questions can be used to identify older individuals who are at risk of needing long-term care. METHODS: This cohort study was conducted in Kobe city, Japan. In 2015, the municipal office distributed the Kihon Checklist by post, a 25-item questionnaire including three cognitive function-related questions (questions 18, 19, 20) to citizens aged ≥ 70 years. Need certification is routinely done by Kobe city as part of the national Long-Term Care Insurance Act. The answers to the 2015 questionnaire were merged with need certification data between the questionnaire delivery and the end of December 2019. RESULTS: Of the 77,877 citizens (age: 72.9 ± 2.7 years) who received the questionnaire, 50,154 responded (response rate: 64.4%). During the study period, the cumulative incidence of the need for long-term care was higher in those who did not respond than in those who did (12.5% vs 8.4%; P < 0.001). Among those who responded, the incidence of the need for long-term care was progressively greater as the number of negative answers to cognitive function-related questions increased (5.0%, 8.4%, 15.7% and 30.2% at 4 years' follow-up, for respondents with, respectively, 0, 1, 2 and 3 negative answers). Similarly, when the need certification for long-term care was confined to that accompanied by dementia, the incidence also rose as the number of negative responses to the cognitive function-related questions increased (3.4%, 6.5%, 13.7% and 27.9% for respondents with, respectively, 0, 1, 2 and 3 negative answers). Using multivariate Cox regression analysis, all three cognitive function-related questions were predictive of the need for long-term care, and question 18 (about memory loss) had the highest hazard ratio for predicting the need for long-term care accompanied by dementia. CONCLUSIONS: Use of cognitive function-related simple questions may help identify older adults at risk for needing long-term care, suggesting their potential value for use in administrative and policy approaches aimed at reducing the societal burden of dementia.Nov. 2022, Health research policy and systems, 20(Suppl 1) (Suppl 1), 120 - 120, English, International magazine[Refereed]Scientific journal
- OBJECTIVES: The purpose of this multicenter retrospective study was to investigate the demographic characteristics and treatment outcomes of patients with mucosal malignant melanoma (MM) of the oral cavity. MATERIALS AND METHODS: This was a multicenter study involving 8 Japanese universities. The medical records of 69 patients who were diagnosed with primary oral MM between January 2000 and December 2020 were retrospectively analyzed. Overall survival (OS) and prognostic factors for OS were analyzed statistically. RESULTS: There were 40 (58.0%) males and 29 (42.0%) females, and their mean (range) age was 69.8 ± 14.6 (22-96) years old. The most common primary site was the palate (30 patients, 43.5%). Stage IVA was the most common disease stage (36 patients, 52.2%). Radical therapy was performed in 55 patients (79.7%). The 2-year and 5-year OS rates of the 69 patients were 64.6% and 42.5%, respectively. The 2-year and 5-year OS rates of the stage III patients were 85.9% and 72.5%, respectively, and those of the stage IVA patients were 56.3% and 26.0%, respectively. The 1-year OS rate of the stage IVB/IVC patients was 26.7%. The 2-year and 5-year OS rates of the radical therapy group were 74.1% and 50.5%, respectively, whereas the 2-year OS rate of the non-radical therapy group was 26.0%. An advanced T classification was the only identified prognostic factor for OS (hazard ratio: 6.312, 95% confidence interval: 1.133-38.522, p < 0.05). CONCLUSIONS: Early detection and radical treatment are essential for improving the prognosis of oral MM patients. CLINICAL RELEVANCE: Early detection and adequate radical therapy leads to the better prognosis of oral MM patients.Aug. 2022, Clinical oral investigations, 26(10) (10), 6187 - 6193, English, International magazine[Refereed]Scientific journal
- PURPOSE: Although the usefulness of polyglycolic acid (PGA) sheet for wound dressing has been recently reported, its histopathological effect on wound healing is not completely elucidated. This pilot study focused on the neo-epithelium formation and the remaining inflammation. METHODS: Full-thickness defects of 8 mm were created on the back of seven-week-old rats. Four rats were divided into the control (raw surface) group and the PGA group, in which the wounds were covered with a PGA sheet. The wounds were assessed on days seven and 12 after wound creation. The length of neo-epithelium on day seven was measured by referring to Masson's trichrome (MT) and α-smooth muscle actin (α-SMA) staining. The remaining inflammation on days seven and 12 was assessed with ionized calcium-binding adapter molecule 1 (Iba-1) staining. RESULTS: The average values of neo-epithelium length on day seven measured by referring to the borderline between MT staining and α-SMA expression were 959.2 μm in the control group and 582.2 μm in the PGA group. The number of Iba-1-positive cells on day 12 was significantly higher in the PGA group than in the control group. CONCLUSIONS: To assess the neo-epithelium length and the remaining inflammation, the α-SMA, MT, and Iba-1 staining may be appropriate.Lead, Cureus, Inc., Jul. 2022, Cureus, 14(7) (7), e27209, English, International magazine[Refereed]Scientific journal
- INTRODUCTION: Scarring and pain are postoperative complications in patients after head and neck cancer treatment; however, there is no effective treatment. These complications are affected by local blood flow disorders, and it is well known that the transcutaneous application of carbon dioxide (CO2) improves local blood flow. Previously, we have shown that the transcutaneous application of carbon dioxide causes absorption of CO2 and increase the oxygen (O2) pressure in the treated tissue; it is expected that the application of CO2 may reduce scarring and pain caused by cancer treatment. We newly introduced the CO2 paste as a new CO2 application method, which does not need to use CO2 gas directly. In this study, we aimed to apply of CO2 paste to healthy people and to investigate its usefulness, safety and feasibility by analysing the increase in blood flow and frequency of adverse events. METHODS: We applied carbon dioxide paste to skin over the sternocleidomastoid and gastrocnemius muscles of eight healthy volunteers. The changes in blood flow before and after the CO2 paste application using dynamic MRI, and changes in the vital signs were evaluated. RESULTS: In the neck area and middle layer of the lower leg, the signal intensity (SI) significantly increased 60 seconds after application. In the surface layer of the lower leg, the SI was significantly increased 60 and 300 seconds after paste application. Although mild heat was noted after the paste application, no obvious adverse events occurred. CONCLUSION: We demonstrated the increase in SI by dynamic MRI at the site of the carbon dioxide paste application, which indicates the paste application is effective in improving the blood flow.Jul. 2022, Medicine, 101(29) (29), e29511, English, International magazine[Refereed]Scientific journal
- Our aims were to determine the clinical impact of oral valganciclovir (VGCV) in infants aged ≤2 months with congenital cytomegalovirus (CMV) disease and evaluate the efficacy of VGCV when initiated beyond the neonatal period. The multicenter, single-arm, open-label clinical trial was conducted in Japan. Twenty-five infants aged ≤2 months with congenital CMV disease involving the central nervous system were enrolled and treated with VGCV for 6 months. The primary endpoint was the change in the whole blood CMV load before and after treatment. The secondary endpoint was the change in the auditory brainstem response (ABR) before and after treatment. Changes in ABR were assessed between the younger and older age groups (≤ and >30 days at treatment initiation). Of the 25 patients, one was excluded owing to epilepsy before VGCV administration. The median change in the CMV DNA level in whole blood was -246.0 IU/mL. The best ear and total ear assessments based on ABR were categorized as (improved + unchanged) after treatment for 100% and 93.8%, respectively. No differences in hearing efficacy were observed between the younger and older age groups. Oral VGCV is a potential therapeutic option for treating infants aged ≤2 months with congenital CMV disease.Jun. 2022, Journal of clinical medicine, 11(13) (13), English, International magazine[Refereed]Scientific journal
- BACKGROUND: Extraction of mandibular third molars is one of the most commonly performed oral surgical procedures, and non-steroidal anti-inflammatory drugs (NSAIDs) are widely used for pain management. Oral NSAIDs are associated with adverse events such as gastrointestinal disorders, renal and hepatic dysfunction, and platelet dysfunction. Topical analgesics have been proposed as an alternative to oral and injectable medications to safely improve postoperative pain relief. We will conduct a single-center, placebo-controlled, double-blind, randomized crossover trial to assess the pain-relieving effect of an ibuprofen-containing gargle in patients undergoing extraction of mandibular third molars compared with a placebo gargle. OBJECTIVE: This will be the first clinical study to evaluate the efficacy of an ibuprofen gargle vs placebo for relieving postoperative pain in addition to loxoprofen after mandibular third molar extraction. METHODS: This study will be performed at Kobe University Hospital. Participants (n = 40) will be randomized equally to one of two groups. The ibuprofen-placebo group will receive an ibuprofen gargle on postoperative day (POD) 1 and a placebo gargle on POD 2. The placebo-ibuprofen group will receive a placebo gargle on POD 1 and an ibuprofen gargle on POD 2. Both groups will receive ibuprofen gargles on PODs 3-5 at least once daily. The primary objective is to estimate the within-subject difference in a visual analogue scale (VAS) before and 5 minutes after using an ibuprofen or placebo gargle on PODs 1 and 2. The secondary objectives are to estimate the within-subject difference in ΔVAS before and 15 minutes after using an ibuprofen or placebo gargle on PODs 1 and 2, ΔVAS before and 5 or 15 minutes after using an ibuprofen gargle on PODs 3-5, overall efficacy (self-completion, five scales) on PODs 1-5, daily frequency of use (ibuprofen or placebo gargle and analgesics) on PODs 1-7, and the occurrence of adverse events. RESULTS: The Kobe University Certified Review Board approved the study. The intervention was implemented in May 2021. For the primary analysis, we will calculate the mean and standard deviation of ΔVAS5 on PODs 1 and 2 and the within-study difference in ΔVAS5. The treatment effect will be estimated by dividing the mean difference in the within-subject difference in ΔVAS5 by 2 and calculating the P-value using an unpaired t-test. For the secondary analysis, we will calculate the mean and standard deviation of ΔVAS15 on PODs 1 and 2 and the within-study difference in ΔVAS15. The treatment effect will be estimated as for the primary analysis. CONCLUSIONS: This trial will provide exploratory evidence of the efficacy and safety of an ibuprofen gargle for pain reduction after mandibular third molar extraction. CLINICALTRIAL: Japan Registry of Clinical Trials jRCTs051210022, https://jrct.niph.go.jp/en-latest-detail/jRCTs051210022.{JMIR} Publications Inc., May 2022, JMIR research protocols, 11(5) (5), e35533, English, International magazine[Refereed]Scientific journal
- (一社)日本認知症予防学会, Mar. 2022, 日本認知症予防学会誌, 11(2) (2), 2 - 8, EnglishPreliminary evaluation of the Japanese version of the Cognitive Function Instrument in a memory clinic(和訳中)[Refereed]
- BACKGROUND: With the rapid increase in the average age of society, the number of people with dementia has increased in Japan. Thus, the need to prevent dementia is greater, and prevention programs have been implemented throughout Japan. This study aims to evaluate both the short-term and the long-term effects of a dementia prevention program on physical and cognitive function in community-dwelling elderly. METHODS: Cognitive and physical assessments were carried out at baseline for a sample including 57 elderly participants. The participants underwent an intensive training program lasting for 2 h per week for 10 days. After the last period of training, the assessment performed was reapplied. The outcome measures used to establish effectiveness were a Mini-Mental State Examination, Five Cognitive Tests, a Cognitive Function Instrument, a Timed Up & Go Test, a grip strength evaluation, a Geriatric Depression Scale, an EQ-5D and a Physical Activity Scale for the Elderly. Participants were then divided randomly into two groups: a booster group and a non-booster group. The booster group received booster training every 3 months after the intensive training period, whereas the non-booster group did not. Both groups were monitored every 6 months for approximately two and a half years after baseline assessment. RESULTS: The Mini-Mental State Examination, the subtests of the Five Cognitive Tests (attention, memory, language and reasoning) and the Timed Up & Go Test revealed a significant improvement after intensive training. For most of the outcome measures, the booster training showed no additional significant improvements. CONCLUSIONS: In this study, intensive training had a short-term positive effect. Although the effect of the booster training was not clear, the functions of the elderly participants were found to be maintained during a follow-up assessment. The study findings recommend conducting intensive training for the community-dwelling elderly without follow-up training.Wiley, Jan. 2022, Psychogeriatrics, 22(1) (1), 113 - 121, English, International magazineScientific journal
- わが国における臨床研究環境は近年著しく変化している。なかでも2018年4月1日に臨床研究法が施行されたことは大きな転換点といえる。その背景として2013年から2014年にかけて、ディオバン事件を代表とする臨床研究に関する不適切な事案が複数生じたことが挙げられる。それらの臨床研究では、複数の大学機関が関連していたデータ操作・不透明な奨学寄附金を通じた研究者と製薬企業との関係性が大きくクローズアップされ、社会問題化した。これらの研究不正に鑑みて、厚労省は、臨床研究の信頼の回復のためには法規制が必要との結論に達し、倫理指針の改定・厳格化を経て臨床研究法施行の運びとなった。臨床研究に関わる全てのものにとって本法の要請を理解し、適切に対応することが求められている一方で、本法を理解するための文書類の多さや手続きの煩雑さなど、研究者の負担が大きく増えたことから、臨床試験の停滞や萎縮を招いている。本法の大きな特徴として、研究責任医師に臨床研究の責任が集約されたこと、研究者は厚労省が認定した認定臨床研究審査委員会を通して試験計画を厚労省に届けること、利益相反の流れが詳細に定められたことなどが挙げられる。本報告では臨床研究倫理における臨床研究法成立までの臨床研究環境の変化について述べたうえで、臨床研究法について概説する。(著者抄録)(一社)日本口腔腫瘍学会, Dec. 2021, 日本口腔腫瘍学会誌, 33(4) (4), 159 - 163, Japanese
- INTRODUCTION: Delayed wound healing after surgery lowers the long-term quality of a patient's life and leads to discomfort and pain. However, treatments for wound healing are often difficult and have not yet been fully established. In this study, we investigated the effect of a special paste that can be administered transdermally and holds a non-gaseous carbon dioxide (CO2) source in its carrier, which can be applied to the head and neck region for wound healing in a rat skin defect model. METHODS: Forty-eight Sprague Dawley rats were randomized into control and CO2 groups. We punched a 6.2-mm wound on the back of each rat. The control rats were left untreated, whereas rats in the CO2 group were treated with the CO2 paste every day after surgery. We evaluated wound healing 3, 7, 14, and 21 days after wounding by analyzing the diameter of the wound, gene expression of inflammatory markers vascular endothelial growth factor (VEGF), transforming growth factor (TGF)-β, hypoxia-inducible factor (HIF)-1α, interleukin (IL)-1β, and IL-6 using quantitative real-time polymerase chain reaction, hematoxylin and eosin, and immunohistochemical staining patterns. RESULTS: Rats in the CO2 group showed accelerated wound healing compared to those in the control group. Furthermore, VEGF and TGF-β were overexpressed, whereas HIF-1α, IL-1β, and IL-6 were downregulated in the rats treated with CO2. Immunohistochemical analysis also revealed similar patterns of expression. CONCLUSION: Taken together, the CO2 paste promoted wound healing by regulating the hypoxic environment, reducing inflammation, and accelerating angiogenesis.Nov. 2021, Cureus, 13(11) (11), e19518, English, International magazine[Refereed]Scientific journal
- OBJECTIVE: The blowing time ratio, which is the ratio of the blowing time when the nostrils are open and closed, is significantly correlated with velopharyngeal pressure, not only during speech but also during swallowing. This study aimed to further evaluate the usefulness of the blowing time ratio as a screening tool to evaluate the swallowing pressure of patients treated for oral and oropharyngeal cancers using high-resolution manometery (HRM). METHODS: Ten patients treated for oral or oropharyngeal cancer were recruited for this study. Swallowing pressures at the velopharynx, oropharynx, and upper esophageal sphincter (UES) were measured using HRM. Their correlations with the blowing time ratio were analyzed. RESULTS: The blowing time ratio was significantly correlated with the swallowing pressures of the oropharynx (CC = 0.815, p = 0.004) and the velopharynx (CC = 0.657, p = 0.039), but not of the UES. CONCLUSIONS: The present results further support our previous finding that the blowing time ratio is a useful screening tool to evaluate velopharyngeal and oropharyngeal swallowing pressures in patients treated for oral and oropharyngeal cancer.Nov. 2021, Auris, nasus, larynx, 49(3) (3), 477 - 483, English, International magazine[Refereed]Scientific journal
- OBJECTIVES: This study aimed to retrospectively investigate the success and survival rates of dental implants used for dentomaxillary prostheses at our hospital and the risk factors associated with large bone defects. MATERIALS AND METHODS: A total of 138 external joint system implants used for dentomaxillary prostheses in 40 patients with large bone defects were included in this study. The alveolar bone at the site of implant insertion was evaluated using panoramic radiography and computed tomography. Various risk factors (demographic characteristics, dental status, and operative factors such as the employment of alveolar bone augmentation, the site, the length, and diameter of implants) for implant failure and complete implant loss were investigated using univariate and multivariate analyses. The associations between the variables and the success and survival rates of dental implants were analyzed using the multivariate Cox proportional hazard models. RESULTS: The 10-year overall success and survival rates were 81.3% and 88.4% in this study. Multivariable analysis showed that the male sex (HR 6.22), shorter implants (≤ 8.5 mm) (HR 5.21), and bone augmentation (HR 2.58) were independent predictors of success rate. Bone augmentation (HR 5.14) and narrow implants (≤ 3.3 mm) (HR 3.86) were independent predictors of the survival rate. CONCLUSION: Male sex, shorter or narrow implants, and bone augmentation were independent risk factors for dental implants used in dentomaxillary prostheses in patients with large bone defects. CLINICAL RELEVANCE: Clinicians should consider these risk factors and pay close attention to the management of these patients.Nov. 2021, Clinical oral investigations, 26(3) (3), 2743 - 2750, English, International magazine[Refereed]Scientific journal
- INTRODUCTION: In recent years, the tumour immunosuppressive mechanism has attracted attention as a cause of tumour chemoresistance. Although chemoresistance and immunosuppression of tumours have been reported to be associated with a hypoxic environment, effective treatments to improve hypoxia in tumours have not yet been established. We have previously applied carbon dioxide (CO2) to squamous cell carcinoma and have shown that improvement in local oxygenation has an antitumour effect. However, the effects of local CO2 administration on tumour immunosuppression, chemoresistance, and combination with chemotherapy are unknown. In this study, we investigated the effects of local CO2 administration on squamous cell carcinoma and the effects of combined use with chemotherapy, focusing on the effects on tumour immunosuppressive factors. METHODS: Human oral squamous cell carcinoma (HSC-3) was transplanted subcutaneously into the back of a nude mouse, and CO2 and cisplatin were administered. After administration twice a week for a total of 4 times, tumours were collected and the expression of tumour immunosuppressive factors (PD-L1, PD-L2, and galectin-9) was evaluated using real-time polymerase chain reaction and immunostaining. RESULTS: Compared with the control group, a significant decrease in the mRNA expression of PD-L1 was observed in both, CO2-treated and combination groups. Similarly, the expression of PD-L2 and galectin-9 decreased in the CO2-treated and combination groups. Furthermore, immunostaining also showed a significant decrease in the protein expression of tumour immunosuppressive factors in the CO2-treated and combination groups. CONCLUSION: It was confirmed that the tumour immunosuppressive factors decreased due to local CO2 administration to the mouse model. CO2 administration has the potential to improve the hypoxic environment in tumours, and combined use with chemotherapy may also improve tumour immunosuppression.Jul. 2021, BioMed Research International, 2021, 5568428 - 5568428, English, International magazine[Refereed]Scientific journal
- INTRODUCTION: This research project addresses the lack of screening tools for the early detection of high-risk individuals for long-term care, through four individual studies.Study 1 investigates the predictive ability of the 'Kihon Check List', study 2 the 'Cognitive Function instrument' and EuroQol-5 Dimension (EQ-5D) and study 3 the 'Cognitive Function instrument' and EQ-5D as well as the 'Frail Kenshin' health check-up, for incident long-term care certification over a follow-up period of up to 4 years. This is the first large prospective study to evaluate the predictive ability of these tools for the outcome measure long-term care certification. The last subsection of this project study four aims to explore a mixed methods intervention for delaying the need for long-term care. This section is purely exploratory, looking for clues for further studies. METHODS AND ANALYSIS: Baseline data have been collected through local government programs, as well as through postal self-reported questionnaires. The primary outcome variable for all studies is long-term care certification data. Statistical analysis will be carried out using Kaplan-Meier, Multiple Cox regression as well as logistic regression. CONCLUSION: This project hopes to identify tools effective in predicting long-term care need. This will enable identification of citizens that are of higher risk for long-term care in the near future. This subset of high-risk individuals can in the future be addressed for extra support/intervention. ETHICS AND DISSEMINATION: All studies have been approved by respective institutional ethical committees and the WHO ethical committee ERC.0002899. In addition, all studies conform to the provisions of the Declaration of Helsinki and are conducted in accordance with Japan's 'Ethical Guidelines for Medical and Health Research Involving Human Subjects'. All findings will be disseminated at conferences and published in peer-reviewed journals. TRIAL REGISTRATION NUMBER: UMIN000023283.Corresponding, Jun. 2021, BMJ open, 11(6) (6), e050948, English, International magazine[Refereed]Scientific journal
- Optical frequency domain imaging (OFDI) is a high-resolution intracoronary imaging modality with fast automated longitudinal pullback. We aimed to evaluate the ability of performing OFDI from the superficial femoral artery (SFA) to the below-knee (BK) artery. This clinical trial was a multi-center, single-arm, open-label study. The primary endpoint was to obtain a clear image of the intra-vascular lumen from the SFA to the BK artery, specifically > 270° visualization of the blood vessel lumen with > 16/21 cross sections. The proportion of the clear image (≥ 85%) was regarded as confirmatory of the ability of OFDI to visualize the vessel lumen. Overall, 20 patients were enrolled. The proportion of the primary endpoint was 90% (18/20), and the pre-specified criterion was successfully attained. The proportion of the clear image assessed by the operator was 100% (20/20), and an additional statistical analysis for the proportion of the visualization, > 270°, of the blood vessel lumen revealed a significantly higher cut-off value than that for the pre-specified criterion, 85% (p = 0.0315). There were three adverse events not related to OFDI. OFDI achieved acceptable visualization of the vessel lumen without any adverse event related to it. After regulatory approval based on the present study, OFDI will be available as a new option of endovascular imaging for peripheral artery diseases in daily practiceTrial registration: This study was registered in the Japanese Registry of Clinical Trials (jRCT 2052190025, https://jrct.niph.go.jp/latest-detail/jRCT2052190025 ).SPRINGER, Jun. 2021, Heart and vessels, 36(6) (6), 818 - 826, English, Domestic magazine[Refereed]Scientific journal
- Purpose Recurrence in oral squamous cell carcinoma (OSCC) is not rare. Due to lack of studies assessing characteristics of recurrent OSCC, including time to recurrence and outcomes, we sought to investigate its characteristics, time to recurrence, and outcomes in Japanese OSCC patients. Methods This study was a nonrandomized retrospective cohort study in a tertiary referral centre. It included 208 (117 men and 91 women) patients with recurrent oral cancer who underwent major curative surgery in the Department of Oral and Maxillofacial Surgery at Kobe University Hospital between January 1999 and April 2017. The outcomes were disease-specific survival (DSS) and overall survival (OS). Results In multivariable Cox proportional hazards analysis, the time to recurrence (hazard ratio [HR] 3.55, 95% confidence interval [CI] 1.69-6.63; P = 0.001), extranodal extension (ENE, HR 2.72, 95% CI 1.51-4.89; P = 0.001), and high T stage (HR 2.00, 95% CI 1.01-3.97; P = 0.046) were independent predictors of DSS. The time to recurrence (HR 3.29, 95% CI 1.82-5.96; P < 0.001) and ENE (HR 2.64, 95% CI 1.52-4.56; P = 0.001) were independent predictors of OS. Conclusion Time to recurrence, extranodal extension, and higher T stage were independent prognosis predictors in OSCC.SPRINGER INDIA, Feb. 2021, JOURNAL OF MAXILLOFACIAL & ORAL SURGERY, 21(3) (3), 856 - 864, English, International magazine[Refereed]Scientific journal
- BACKGROUND: This prospective study investigated the change of swallowing ability using the Swallowing Ability Scale System (SASS) and swallowing-related quality of life (QOL) by Performance Status Scale for Head and Neck Cancer patients (PSS-H&N). This study also investigated the risk factors for postoperative dysphagia in patients who received reconstructive surgery for oral cancer. SUBJECTS AND METHODS: This study included 64 patients (33 men and 31 women) who underwent radical surgery with neck dissection and reconstructive surgery for oral cancers between July 2014 and February 2018. We evaluated risk factors for poor swallowing ability after treatment, including demographic factors, preoperative factors and perioperative factors, with univariate and multivariate analyses. The change of swallowing ability by the SASS and swallowing-related QOL by PSS-H&N were evaluated prospectively prior to the initiation of surgery within 1 week and at 1 and 3 months after treatment. RESULTS: Advanced T stage (T3, 4) (odds ratio (OR) = 79.71), bilateral neck dissection (OR = 20.66) and the resection of unilateral or bilateral suprahyoid muscles (OR = 17.00) were associated with poor swallowing ability after treatment. The scores for time for food intake and Eating in Public were associated with decrease of QOL in the poor group. CONCLUSIONS: We propose that clinicians consider the risk factors identified in this study and pay close attention to the management of oral cancer patients with reconstructive surgery.BMC, Jan. 2021, Journal of otolaryngology - head & neck surgery = Le Journal d'oto-rhino-laryngologie et de chirurgie cervico-faciale, 50(1) (1), 4 - 4, English, International magazineScientific journal
- Cetuximab, an epidermal growth factor receptor inhibitor (EI), is currently the only targeted molecular therapy used in combination with radiotherapy for head and neck squamous cell carcinoma (HNSCC). Gold nanoparticles (AuNPs) are expected to enhance radiotherapy effects in cancers. To investigate whether AuNPs combined with AG1478, an EI, enhanced irradiation effects on HNSCC cells, we first examined AG1478 adsorption on AuNP surfaces, using surface-enhanced Raman scattering, which indicated an adsorption equilibrium of AG1478 to AuNPs. We then used transmission electron microscopy to find internalization rates of AuNP alone and AuNP+AG1478; we found that intracellular uptake of AuNP alone and AuNP+AG1478 did not significantly differ. We compared cell numbers, proliferation, apoptosis, and migration between control cells and those treated with or without 60 nm AuNP (1.0 nM), AG1478 (0.5 μM), and irradiation (4 Gy). We found that AuNP+AG1478 inhibited proliferation more than AG1478 alone; the combination of irradiation+AuNP+AG1478 significantly reduced total cell numbers compared with the combination of irradiation+AuNP; AuNP+AG1478 increased apoptotic reaction to irradiation; the combinations of AuNP+AG1478 and irradiation+AuNP induced more apoptosis than AG1478+irradiation. Whereas AuNP+AG1478 enhanced cytotoxicity in human HNSCC cells by inhibiting proliferation, irradiation+AuNP enhanced cytotoxicity by inducing apoptosis.Corresponding, HINDAWI LTD, 2020, BioMed Research International, 2020, 1281645 - 1281645, English, International magazine[Refereed]Scientific journal
- PURPOSE: This study retrospectively investigated relationships among risk factors and post-hepatectomy surgical site infection (SSI) and other complications in patients who underwent hepatectomy for hepatocellular carcinoma (HCC). METHODS: We included 334 patients who underwent hepatectomies for liver cancers between January 2011 and December 2015 in this study. We evaluated risk factors for SSI and other post-hepatectomy complication, including demographic factors, preoperative factors, and preoperative intervention including oral management, perioperative factors, and length of hospital stay, with univariate and multivariate analyses. The oral management intervention included self-care instructions, extraction of infected teeth, removal of dental plaques and calculus (scaling), professional mechanical teeth cleaning, removal of tongue coating, and cleaning of dentures. SSI was defined in accordance with the guideline issued by the Centers for Disease Control and Prevention; it included purulent discharge from any incision or organ space within 30 days postoperatively, with or without microbiological evidence. Complications of grade II or greater, according to the Clavien-Dindo classification, were regarded as postoperative complications. RESULTS: We found bacterial infection of ascites (Odds ratio (OR) = 13.72), lack of preoperative oral management intervention (OR = 10.17), and severe liver fibrosis (OR = 2.76) to be associated with SSI and severe liver fibrosis (OR = 2.28), hypoalbuminemia (OR = 2.02), blood transfusion (OR = 1.86), and longer operation time (OR = 1.80) to be associated with postoperative complications. CONCLUSIONS: Preoperative oral management may reduce the risk of SSI in patients with HCC who undergo hepatectomy.SPRINGER, 2020, Supportive Care in Cancer, 29(2) (2), 653 - 659, English, International magazine[Refereed]Scientific journal
- BACKGROUND: Prognostic biomarkers provide essential information about a patient's overall outcome. However, existing biomarkers are limited in terms of either sample collection, such as requiring tissue specimens, or the process, such as prolonged time for analysis. In view of the need for convenient and non-invasive prognostic biomarkers for oral cancer, we aimed to investigate the prognostic values of neutrophil-to-lymphocyte ratio, lymphocyte-to-monocyte ratio, and platelet-to-lymphocyte ratio in patient survival. We also aimed to explore the associations of these ratios with the clinicopathologic characteristics of Japanese oral squamous cell carcinoma patients. METHODS: This study was a non-randomized retrospective cohort study in a tertiary referral center. We included 433 patients (246 men, 187 women) who underwent radical surgery for oral cancers between January 2001 and December 2013. We evaluated various risk factors for poor prognosis including neutrophil-to-lymphocyte ratio, lymphocyte-to-monocyte ratio, and platelet-to-lymphocyte ratio with univariate and multivariate analyses. The disease-specific survival and overall survival rates of patients were compared among the factors and biomarkers. RESULTS: In multivariable Cox proportional hazards analysis, high neutrophil-to-lymphocyte ratio (hazard ratio 2.87, 95% confidence interval 1.59-5.19, P < 0.001), moderately or poorly differentiated histology (hazard ratio 2.37, 95% confidence interval 1.32-4.25, P < 0.001), and extranodal extension (hazard ratio 1.95, 95% confidence interval 1.13-3.35, P = 0.016) were independent predictors of disease-specific survival. High neutrophil-to-lymphocyte ratio (hazard ratio 2.30, 95% confidence interval 1.42-3.72, P < 0.001), moderately or poorly differentiated (hazard ratio 1.72, 95% confidence interval 1.07-2.76, P = 0.025), and extranodal extension (hazard ratio 1.79, 95% confidence interval 1.13-2.84, P = 0.013) were independent predictors of overall survival. CONCLUSIONS: Neutrophil-to-lymphocyte ratio might be a potential independent prognostic factor in Japanese oral squamous cell carcinoma patients.BMC, 2020, BMC Cancer, 20(1) (1), 568 - 568, English, International magazine[Refereed]Scientific journal
- Although balloon angioplasty for femoropopliteal artery lesions has been associated with restenosis rates of up to 60% at 12 months, the mechanism of restenosis has not been fully evaluated. The aim of this study was to evaluate the relationship between the vascular features observed on optical frequency domain imaging (OFDI) before and after balloon angioplasty of femoropopliteal artery lesions, and restenosis at 6 months. This study was a prospective multicenter single arm study. OFDI was performed before and after balloon angioplasty and plaque characteristics and vascular features, along with de novo lesions, were assessed. The primary outcome was the presence or absence of restenosis 6 months after balloon angioplasty. Residual platelet reactivity was assessed according to VerifyNow platelet reactivity units (PRUs). The number of patients completing 6 months of follow-up was 47, of which 14 had developed restenosis. Maximum thickness of the dissection flap (odds ratio (OR) 2.71; 95% confidence interval [0.9-8.0]; p = 0.071) and lesion length were identified as risk factors for restenosis (OR 1.015; 95% confidence interval [0.001-0.029]; p = 0.039). The mean PRU at the time of treatment in patients with restenosis was significantly higher than in those without restenosis (286.3 ± 82.6 vs. 208.5 ± 03.6, p = 0.026). Long lesions and major dissection on OFDI after balloon angioplasty for femoropopliteal artery lesions increase restenosis at 6 months. In addition, high residual platelet reactivity at the time of EVT may also be a risk factor for restenosis.Clinical Trial Registration Number UMIN000021120.SPRINGER JAPAN KK, 2020, Cardiovascular Intervention and Therapeutics, 36(3) (3), 321 - 329, English, Domestic magazine[Refereed]Scientific journal
- BACKGROUND: Congenital cytomegalovirus (CMV) disease, a common mother-to-child infection, can lead to neurological sequelae. Some clinical trials have shown that oral valganciclovir (VGCV) can improve hearing and neurodevelopmental impairment in infants with congenital CMV disease. However, VGCV has neither been approved in Japan nor other countries as a treatment for this disease by the government health insurance. METHODS: This study is a non-randomized, prospective, open-label, multicenter, single-arm clinical trial and will include subjects meeting the following criteria: confirmation of positive CMV-DNA amplification in urine by an in vitro diagnostic test within 21 days of age; congenital CMV disease with one or more central nervous system disorders-microcephaly, hydrocephalus or ventricular enlargement, periventricular calcification, cortical hypoplasia or white matter injury, retinal choroiditis, and abnormal auditory brainstem response (ABR); and infants within 2 months of age with a gestational age ≥32 weeks at birth and weighing ≥1800 g at the time of registration. Subjects will be orally administered 16 mg/kg VGCV twice daily for 6 months. The target number of cases for enrollment between February 3, 2020 and July 31, 2021 is 25. Primary endpoint is the change in whole blood CMV loads before and after 6 months of treatment. The important secondary endpoint is the change in ABR (both best and total ear hearing assessments) before and after 6 months of treatment. The safety endpoints are adverse events and drug side effects. DISCUSSION: To the best of our knowledge, this multicenter, open-label, single-arm study will be the first well-designed clinical trial to evaluate the efficacy of oral VGCV in infants with congenital CMV diseases. The findings will reveal the efficacy and safety of oral VGCV treatments and enable the approval of oral VGCV as a treatment for infants with congenital CMV disease by the government health insurance of Japan.LIPPINCOTT WILLIAMS & WILKINS, 2020, Medicine, 99(17) (17), e19765, English, International magazine[Refereed]Scientific journal
- BACKGROUND: Chronic spontaneous urticaria (CSU) is characterized by the spontaneous appearance of wheals, angioedema, or both for > 6 weeks. Continuous treatment with H1-antihistamines is used as a first-line treatment for CSU. However, H1-antihistamine treatment leads to absence of symptoms in less than 50% of patients with CSU. Although Japanese guidelines for the diagnosis and treatment of urticaria recommend an increase in the H1-antihistamine dose or a switch to other H1-antihistamines, there is no evidence supporting a switch to other H1-antihistamines in patients with refractory CSU who are unresponsive to H1-antihistamines at the licensed dose. METHODS: We will conduct a multicenter, open-label, non-inferiority, randomized, parallel, comparison study to determine if the efficacy of bilastine 20 mg is not inferior to that of a twofold H1-antihistamine dose increase in patients with refractory CSU who are unresponsive to H1-antihistamines at the licensed dose. This study will be performed at 15 academic hospitals in Japan, and the administration period (increasing the H1-antihistamine dose twofold vs. switching to bilastine 20 mg) will be 7 days. Participants (n = 150) will be randomized to either an increased H1-antihistamine dose or a switch to bilastine 20 mg at a 1:1 ratio. The primary endpoint, mean of the total symptom score of 5-7 days after the intervention, will be evaluated. The secondary objective is to determine if the safety of bilastine 20 mg regarding somnolence is superior to that of a twofold dose increase of H1-antihistamines. This will be measured by a change in the Japanese version of the Epworth Sleepiness Scale from baseline to 7 days after starting the intervention. DISCUSSION: This multicenter, open-label, non-inferiority, randomized, parallel, comparison study will be, to our knowledge, the first well-designed clinical study to evaluate the efficacy of a switch to other H1-antihistamines in patients with refractory CSU who are unresponsive to H1-antihistamines at the licensed doses. This trial will provide evidence of the efficacy and safety of bilastine when treatment is switched in patients with refractory CSU who are unresponsive to H1-antihistamines at the licensed dose. TRIAL REGISTRATION: Japan Registry of Clinical Trials (jRCT), jRCTs051180105. Registered on 8 March 2019.BMC, 2020, Trials, 21(1) (1), 23 - 23, English, International magazine[Refereed]Scientific journal
- BACKGROUND: No clear consensus has been reached on the indication of supraomohyoid neck dissection (SOHND) for clinically positive lymph-node metastasis. PATIENTS: Consecutive 100 patients with previously untreated oral cancer treated at Kobe University Hospital were included in this study. All patients were clinically staged as anyTN1M0 and underwent radical dissection of the primary site and level I-V neck dissection as the initial treatment. RESULTS: None of the 100 patients had pathological lymph-node metastasis (pLN) to level V. pLN to level IV was observed in two patients with tongue cancer in whom clinical lymph-node metastasis was preoperatively observed at level II. CONCLUSIONS: Level V may be excluded in the neck dissection for patients with N1 oral cancers. Level IV dissection should be considered in the patient with tongue cancer and clinical lymph-node metastasis at level II.Lead, SPRINGER JAPAN KK, 2020, International Journal of Clinical Oncology, 25(6) (6), 1067 - 1071, English, Domestic magazine[Refereed]Scientific journal
- BACKGROUND: The purpose of this study was to retrospectively describe the characteristics and outcomes of patients with oral squamous cell carcinoma and level IV/V metastasis and to compare patients who underwent no postoperative therapy with those who underwent postoperative radiotherapy (RT) and concomitant chemoradiotherapy (CCRT). METHODS: We evaluated 669 patients. Clinicopathological data, postoperative therapy, and clinical course were investigated. RESULTS: Sixty-one patients (9.1%) developed level IV/V metastasis. The 3-year cumulative overall survival rates of patients with and without level IV/V metastasis were 47.3% and 64.3%, respectively. Tongue tumors, pN2 or N3 classification, and moderate or poor differentiation were significantly associated with the development of level IV/V metastasis. The surgery+RT/CCRT group was associated with better 3-year cumulative disease-specific survival and overall survival rates than the surgery only group. CONCLUSION: Adjuvant therapy (RT alone or CCRT) after surgery is recommended for patients with level IV/V metastasis.WILEY, 2019, Head and Neck, 41(7) (7), 2256 - 2263, English, International magazine[Refereed]Scientific journal
- BACKGROUND: This study aimed to evaluate posttreatment soft-tissue changes in patients with oral cancer with computed tomography (CT). To accomplish that purpose, a scoring system was established, referring to the criteria of lower leg lymphedema (LE). METHODS AND RESULTS: One hundred and six necks in 95 patients who underwent oral oncologic surgery with neck dissection (ND) were analyzed retrospectively using routine follow-up CT images. A two-point scoring system to evaluate soft-tissue changes (so-called "LE score") was established as follows: Necks with a "honeycombing" appearance were assigned 1 point. Necks with "taller than wide" fat lobules were assigned 1 point. Necks with neither appearance were assigned 0 points. Comparisons between patients with LE score ≥1 and LE score = 0 at 6 months postoperatively were performed using the Fisher exact test for discrete variables and the Mann-Whitney U test for continuous variables. Univariate predictors associated with posttreatment changes (i.e., LE score ≥1 at 6 months postoperatively) were entered into a multivariate logistic regression analysis. Values of p < 0.05 were considered to indicate statistical significance. The occurrence of the posttreatment soft-tissue changes was 32%. Multivariate logistic regression analysis showed that postoperative radiation therapy (RT) and bilateral ND were potential risk factors of posttreatment soft-tissue changes on CT images. CONCLUSIONS: Sequential evaluation of "honeycombing" and the "taller than wide" appearances on routine follow-up CT revealed the persistence of posttreatment soft-tissue changes in patients who underwent oral cancer treatment, and those potential risk factors were postoperative RT and bilateral ND.MARY ANN LIEBERT, INC, 2018, Lymphatic Research and Biology, 16(2) (2), 147 - 153, English, International magazine[Refereed]Scientific journal
- BACKGROUND: Oral squamous cell carcinoma (OSCC) containing single lymph node metastasis (pN1) with extra nodal extension (ENE) is a rare clinical situation. Therefore, it is unclear whether pN1 with ENE is at high risk of recurrence among the OSCC population, or whether postoperative radiotherapy (RT)/concomitant chemoradiotherapy (CCRT) is effective in these cases. OBJECTIVES: The purpose of this retrospective study was to investigate the prognosis and compare between no postoperative therapy and postoperative RT/CCRT in pN1 with ENE OSCC patients. METHODS: Clinicopathological data and treatment modalities were investigated. The evaluated endpoints were overall survival (OS) and type of recurrence. RESULTS: The 3-year cumulative OS rates for the pN1 only, multiple lymph node metastasis (MLM) only, ENE + MLM, and ENE + pN1 groups were 77.2%, 66.8%, 43.3%, and 66.6%, respectively. In the ENE + pN1 group, the most common cause of death in the surgery only group was from regional failure. The surgery + RT/CCRT group was associated with better disease-specific survival and OS rates than the surgery only groups (P < 0.05). CONCLUSIONS: The prognosis of ENE + pN1 was not as poor as that of ENE + MLM, although both these groups feature ENE. Adjuvant therapy (RT/CCRT) after surgery is recommend for cases of ENE + pN1.WILEY, 2018, Journal of Surgical Oncology, 117(8) (8), 1736 - 1743, English, International magazine[Refereed]Scientific journal
- BACKGROUND: A problematic complication after radiation therapy is lymphedema. Development of lymphedema is associated with an increase in lymphatic paracellular permeability. The current study investigated the effects of radiation on intercellular junctions and paracellular permeability in cultured human dermal lymphatic endothelial cells (HDLECs). METHODS AND RESULTS: Double immunofluorescence staining with vascular endothelial (VE)-cadherin and actin immediately after X-ray irradiation (5 or 20 Gy) was performed. Morphological changes induced by irradiation were assessed. Cell viability and paracellular permeability after irradiation were also evaluated. Broad junctions in which VE-cadherin was accumulated at cell-cell contacts and almost colocalized with actin were significantly decreased in a dose-dependent manner in confluent and sparse irradiated HDLECs. Irradiation shortened the width of VE-cadherin-positive areas at the cell-cell contacts. Actin filaments did not colocalize with VE-cadherin after 20 Gy irradiation. Although cell viability was not affected by irradiation, paracellular permeability significantly increased in a dose-dependent manner. CONCLUSIONS: A dose of 5 or 20 Gy irradiation in HDLECs does not affect cell viability, but changes VE-cadherin mediated intercellular junctions and actin structure, resulting in an increase of paracellular permeability. Further investigations on the regulatory proteins involved in radiation-induced changes, which were observed in the current study, may contribute to development of lymphedema therapy.MARY ANN LIEBERT, INC, 2018, Lymphatic Research and Biology, 16(4) (4), 390 - 396, English, International magazine[Refereed]Scientific journal
- Enhancing the antitumor effect of radiation, while reducing damage to organs, is a significant challenge in radiation therapy for head and neck malignancies. One promising radiosensitizer is gold. The present study aimed to determine whether gold nanoparticles (AuNPs) have the potential to enhance the effects of X-ray irradiation on head and neck cancer cells. The human head and neck carcinoma cell line HSC-3 was used. Total cell number and the levels of cell proliferation and apoptosis were compared between control cells and cells treated with 5-nm AuNPs alone at four concentrations (0.1, 0.4, 1.0 and 10.0 nM), X-ray irradiation alone at three doses (2, 4 and 8 Gy), or a combination of 4 Gy X-ray irradiation and 1.0 nM AuNPs. Analysis of variance and Tukey-Kramer testing were performed to compare the different groups. The total number of cells significantly decreased following 4 and 8 Gy X-ray irradiation, compared with in the control group (control vs. 4Gy, P=2.19×10-4; control vs. 8Gy, P=1.28×10-6). The combination of 4 Gy X-ray irradiation and 1.0 nM AuNPs significantly reduced the total number of cells compared with 4 Gy X-ray irradiation alone (P=2.95×10-4). Cell proliferation was not affected by AuNP treatment alone, 4 Gy X-ray irradiation alone or the combination of X-ray irradiation and AuNPs. The combination of 4 Gy irradiation and 1.0 nM AuNPs significantly increased the number of apoptotic cells compared with 4 Gy irradiation alone (P=0.0261). In conclusion, AuNPs combined with X-ray irradiation enhanced the cytotoxic effect on human head and neck cancer cells in vitro, through the induction of apoptosis, but not inhibition of cell proliferation.SPANDIDOS PUBL LTD, 2018, Biomedical Reports, 9(5) (5), 415 - 420, English, International magazine[Refereed]Scientific journal
- It was hypothesized that fluorodeoxyglucose (FDG) uptake on post-treatment follow-up positron emission tomography with computed tomography (PET CT; using PET CT to monitor and rule out recurrence and metastasis of head and neck carcinoma) would be useful for detecting and understanding the disease state of osteoradionecrosis (ORN) of the jaw. The present study included 14 patients who developed mandibular ORN following radiation therapy (RT) for head and neck cancer and underwent follow-up PET CT several times following RT. Areas exhibiting FDG uptake were retrospectively assessed on post-treatment follow-up PET CT images and were classified into three types: Spot type: Only spot accumulation of FDG; localized type: Accumulation of FDG restricted to within the bone resorption area; extensive type: Accumulation of FDG extending into surrounding soft tissue. PET classification at the time of clinical diagnosis of mandibular ORN in the 14 patients demonstrated the extensive type in 43%, localized type in 36% and spot type in 21%. An increased area of FDG uptake around the ORN was revealed retrospectively on post-treatment follow-up FDG PET-CT images in 50% of patients. Alterations in PET classification included spot type to localized type in 36% and localized type to extensive type in 14%. A significantly increased number of patients with extensive-type ORN (P=0.026) required surgery. Post-treatment follow-up FDG-PET CT may be useful for early detection and better understanding of ORN.SPANDIDOS PUBL LTD, Nov. 2017, Molecular and Clinical Oncology, 8(1) (1), 61 - 67, English, International magazine[Refereed]Scientific journal
- <p> Although radiation therapy (RT) is the indispensable treatment for head and neck malignancies, one of serious complications is osteoradionecrosis of the jaw (ORN). The most well-known causative factor is surgical trauma (e.g., tooth extraction). We here report a case of osteoradionecrosis of the jaw around dental implants. A 68-year-old female underwent surgery and postoperative chemoradiotherapy for adenoid cystic carcinoma of the left submandibular gland. Three years after RT, she suffered from the right mandibular peri-implant infection, and visited to our department. We diagnosed ORN around the dental implants which were inserted before RT. The long-term conservative treatments such as the oral administration of antibiotics and the local irrigation were performed. Five years after RT, the sequestration with dental implants was removed under the local anaesthesia.</p><p> In general, ORN is difficult to be treated, and the treatment should be determined according to severity of accompanying symptoms and patient's general condition, etc. For prevention of ORN, the strict oral management to maintain good hygiene around dental implants is essential.</p>公益社団法人 日本顎顔面インプラント学会, Aug. 2017, Japanese Journal of MaxilloFacial Implants, 16(2) (2), 75 - 80, Japanese[Refereed]
- PURPOSE: The objectives of this study were to retrospectively describe the characteristics and outcomes of patients with oral squamous cell carcinoma (OSCC) with level IV/V metastases, and to evaluate the multivariate relationships among potential risk factors for metastasis and prognosis. MATERIALS AND METHODS: We evaluated 291 patients (178 men and 113 women; mean age, 65.9 ± 13.5 years). Clinicopathological data, time of development of level IV/V metastases, and clinical course were investigated. RESULTS: Twenty-three patients (7.9%) developed level IV/V metastases. The 3-year overall survival rates when level IV/V metastasis first developed were 27.3% upon initial treatment, 57.1% when metachronous neck metastasis developed, and 40.0% when the tumor recurred. Oral tongue tumor subsite, high N staging, neck dissection when metachronous neck metastasis developed, as well as recurrence were independent risk factors for level IV/V metastasis. CONCLUSION: We demonstrate here the multivariate relationships among the risk factors indicated above for level IV/V metastasis and their prognostic significance for patients with OSCC. Oral tongue tumors, high N staging, and neck dissection upon the occurrence of metachronous neck metastasis or recurrence were risk factors for level IV/V metastasis and positive extracapsular spread, presence of multiple lymph metastases, and moderate or poor differentiation were poor prognostic factors.CHURCHILL LIVINGSTONE, 2017, Journal of Cranio-Maxillofacial Surgery, 45(1) (1), 145 - 149, English, International magazine[Refereed]Scientific journal
- The benefits of epidermal growth factor receptor (EGFR) targeting in the treatment of head and neck cancer, have been documented. However, a minority of patients with head and neck cancer are unresponsive to EGFR targeting therapies. The present study evaluated the effects and limitations of an EGFR inhibitor on oral squamous cell carcinoma cells, particularly on cell-cell junctions mediated by epithelial (E)-cadherin. HSC-3 oral squamous cell carcinoma cells were treated with the EGFR inhibitor, AG1478 (0, 0.5, 2, 10 and 50 µM), and the effects of EGFR inhibition in HSC-3 cells were evaluated by wound healing assays, E-cadherin immunostaining and measurement of transepithelial electrical resistance in vitro. It was observed that treatment of oral squamous cell carcinoma cells with AG1478 suppressed cell motility, altered cell morphology and increased the number of cell-cell junctions compared with untreated control cells. Knockdown of EGFR induced a similar phenotype to that observed by the inhibition of EGFR. Furthermore, in oral squamous cell carcinoma cells treated with high-dose EGFR inhibitor (50 µM), the small number of cells that survived formed cell-cell junctions that were positive for E-cadherin expression. In cells treated with low concentrations of EGFR inhibitor (2 µM), recovery of epithelial properties was observed. The retention of E-cadherin expression in cells that survived high-dose EGFR inhibitor treatment may be a survival mechanism of cancer cells.Lead, SPANDIDOS PUBL LTD, 2017, Experimental and Therapeutic Medicine, 14(2) (2), 953 - 960, English, International magazine[Refereed]Scientific journal
- OBJECTIVE: Few studies evaluate condylar movement following mandibular reconstruction. The main objective of this study was to show that axial four-dimensional computed tomography (4DCT) could visualize bilateral protrusive condylar movement directly. We used axial 4DCT images to assess condylar protrusion in patients who underwent mandibular reconstruction. METHODS: We enrolled seven healthy volunteers (median age 30 years, range 27-38 years) and seven patients (median age 65 years, range 52-80 years), who underwent mandibulectomy (segmental in five, hemi in one, marginal in one) and free flap reconstruction (using the fibula in six and the radial forearm in one). Six study subjects were instructed to masticate a cookie during the 4DCT scan (the seventh made chewing motions). The distance between the most anterior and posterior positions of the bilateral condyles on 4DCT (axial view) images was then measured and compared between controls and patients using the Mann-Whitney U-test. RESULTS: The crosswise difference in the distances of condylar protrusion was significantly greater in patients than in the controls. CONCLUSION: Axial 4DCT images can visualize a bilateral condylar protrusive path. Axial 4DCT images for patients who have undergone mandibulectomy and reconstruction may be useful for evaluation of functional movement of condyles.CHURCHILL LIVINGSTONE, 2017, Journal of Cranio-Maxillofacial Surgery, 45(11) (11), 1778 - 1783, English, International magazine[Refereed]Scientific journal
- Objective: Dental injury is the most common complication of general anaesthesia. The primary purpose of this study was to report the occurrence, location, type, and treatment of dental injury caused by endotracheal intubation.Methods: This retrospective study evaluated 36,627 cases of general anaesthesia at our hospital from January 2008 through December 2015. The examination items included risk factors such as age; sex; surgical department; type of intubation(orotracheal or nasotracheal intubation); presence of preoperative trismus; Cormack-Lehane classification; experience of the attending anaesthesiologist; intubation appliance; mouth guard use; tooth mobility diagnosed by attending anaesthesiologist before surgery; the location, type, and treatment of injured teeth; and forensic implications.Results: The incidence of dental injury was 0.06% (22 of 36,627 patients). There was a significant difference in the rate of dental injury according to age (0.026% among those <60 years of age vs. 0.096% among those >= 60 years; P < 0.05) and according to surgical department (0.189% among neurosurgery patients; P < 0.05). The most common Cormack-Lehane classification of laryngeal view in the 22 patients with dental injury was grade 2 (50%). Tooth mobility was diagnosed by anaesthesiologists in 50% of injured patients before surgery. There was no preoperative dental consultation in our department in any of the patients with injured teeth.Conclusions: Dental screening is recommended for patients in whom anaesthesiologists find mobile teeth and difficult intubation. A system to facilitate cooperation between anaesthesiologists and dental surgeons should be established. (c) 2017 Asian AOMS, ASOMP, JSOP, JSOMS, JSOM, and JAMI. Published by Elsevier Ltd. All rights reserved.Lead, ELSEVIER SCIENCE INC, 2017, Journal of Oral and Maxillofacial Surgery, Medicine, and Pathology, 29(6) (6), 518 - 521, English[Refereed]Scientific journal
- The submandibular gland (SMG) is one of the major salivary glands that play important roles for variety of physiological functions, such as digestion of foods, prevention of infection, and lubrication of the mouth. Dysfunction of the SMG, often associated with a salivary inflammation, adversely influences a person's quality of life. However, the mechanism underlying inflammation-driven dysfunction of the SMG is largely unknown. Here, we used a mouse model in which the main excretory duct of the SMG is ligated unilaterally to induce inflammation of the gland and examined the expression of Wnt5a, Ror1 and Ror2 genes, encoding Wnt5a ligand and its cognate receptors, which have been implicated in tissue damage or inflammatory responses in variety of tissues. We show that expression levels of Ror1, Ror2, and Wnt5a are increased in the ligated SMG undergoing interstitial fibrosis, which is accompanied by robust expression of fibrosis-associated genes, such as TGF-β1, TNF-α, IL-1β, and MMP-2. Increased immunostaining signal of Ror2 was detected in the fibrotic tissues with abundant accumulation of fibroblasts and collagen fibers in the ligated SMG, suggesting that Ror2-mediated signaling might be activated in response to tissue damage and associated with progression of fibrosis in the SMG.Key words: submandibular gland, Ror2, Wnt5a, fibrosis, inflammation.2017, Cell Structure and Function, 42(2) (2), 159 - 167, English, Domestic magazine[Refereed]Scientific journal
- A case series of fibro-osseous lesions of the jawsThe aim of this case series was to reveal the difficulties in diagnosing fibro-osseous lesions with radiological and histopathological examinations and quantify the potential risk of infection to fibro-osseous legions. To analyze the concordance between radiological and histopathological diagnoses, this retrospective case series included patients who were clinically diagnosed with fibro-osseous lesions via radiological findings and excluded the patients who did not undergo histopathological examinations. This study also included the patients in whom histopathological results confirmed fibro-osseous legions when preoperative radiological diagnosis did not include fibro-osseous legions. Eleven patients (three men, eight women; median age 24.5 years, range 15-57 years) were enrolled. Although radiological diagnoses of fibrous dysplasia (FD) corresponded with histopathological diagnoses in seven patients, mismatches between radiological findings and histopathological results were found in three patients. In one patient, suspected diagnosis with radiological examinations was malignant lymphoma or FD. In two patients, the histopathological differentiation between FD and ossifying fibroma (OF) was difficult. One patient had lesion recurrence which was suspected to be OF with surgical findings and postoperative course after the initial surgery. In three patients, infections of FD were found. Preoperative diagnosis of OF with radiographic feature of unilocular radiolucency is difficult. In cases in which histopathological differentiation between FD and OF is difficult, operative findings should be used because OF is often found to be well-encapsulated and easily enucleated. Bone in FD showing mixed radiolucent-radiopaque may be vulnerable to infection.2017, Kobe Journal of Medical Sciences, 63(3) (3), E73-E79 - E79, English, Domestic magazine[Refereed]Scientific journal
- Clinical Analysis of Tooth Injuries in Elderly Person外傷歯の特徴は年齢層で相違がある。今回われわれは、高齢者の外傷歯の特徴を明らかにする目的で、2008年1月から2015年12月までに神戸大学医学部附属病院歯科口腔外科を受診した外傷歯患者188例(497歯)を対象に調査した。対象症例の年齢を世代別に0〜12歳:43例(93歯)、13〜39歳:81例(215歯)、40〜64歳:38例(108歯)、65歳以上:26例(80歯)の4つのグループに分類した。男女比は全体では1.6:1で男性に多かったが、65歳以上では女性の比率が高かった。受傷原因では、0〜12歳と65歳以上では転倒が高い割合を示した。顎骨骨折は13〜39歳で最も多く認められ、65歳以上の割合は30.8%であった。歯の受傷様式では、全世代で不完全脱臼の頻度が高く、65歳以上では歯根破折の割合が他の世代より高かった。老齢人口は増加し続けることから、高齢者の外傷歯も増加すると予測される。高齢者の顎顔面外傷を予防するための対策の検討が必要である。(著者抄録)日本外傷歯学会, Dec. 2016, 日本外傷歯学会雑誌, 12(1) (1), 53 - 59, Japanese
- PURPOSE: Patients with oral cancer who undergo resection with simultaneous reconstruction are presumed to be at high risk for developing venous thromboembolism (VTE) according to current criteria. The primary purpose of this retrospective study was to report the incidence of VTE after oral cancer surgery requiring primary reconstruction and to identify the potential risk factors for VTE in this population. MATERIALS AND METHODS: This retrospective study evaluated 133 consecutive patients who had undergone oral cancer resection with simultaneous reconstruction from April 2007 through December 2014. Bilateral lower-extremity venous duplex ultrasonography (VDUS) was routinely performed 2 days after surgery. Pulmonary embolism was confirmed with computed tomography. The Caprini risk score (CRS) was obtained for each patient. Patients with and without VTE were compared using the χ2 test and Student t test with some variables. Univariate predictors associated with VTE were entered into a multivariate logistic regression analysis. A P value less than .05 was regarded as indicating statistical significance. RESULTS: The incidence of VTE after oral oncologic surgery with simultaneous reconstruction was 26.3% (35 of 133 patients): deep vein thrombosis (DVT) and pulmonary embolism occurred in 2.3% (3 of 133) and DVT alone was found in 24.0% (32 of 133). Multivariate logistic regression analysis showed that only a high CRS was statistically relevant to VTE occurrence. CONCLUSIONS: Because a high incidence of VTE was found after major oral and maxillofacial surgery, lower-extremity VDUS should be undertaken in patients who undergo oral cancer surgery with simultaneous reconstruction, especially those with a high CRS.Lead, W B SAUNDERS CO-ELSEVIER INC, 2016, Journal of Oral and Maxillofacial Surgery, 74(1) (1), 212 - 7, English, International magazine[Refereed]Scientific journal
- PURPOSE: The purpose of this study was to analyze jaw movement during mastication in patients who underwent mandibular reconstruction following segmental mandibulectomy, including mouth opening and mastication time, based on four-dimensional computed tomography (4D CT) images. MATERIAL AND METHODS: This study included six surgical patients, who underwent segmental mandibulectomy and simultaneous reconstruction with a free fibula osteocutaneous flap, and four controls. 4D CT was performed during mastication of a cookie to evaluate the movement of the jaw during natural function. The maximum mouth opening, mastication time, and movement of the mandibular angle during mastication were evaluated from the 4D CT images. RESULTS: 4D CT images enabled visualization of jaw movement during mastication. When compared with the controls, the maximum mouth opening during mastication and excursion of the mandibular angle, especially on the diseased side, tended to decrease in surgical patients; however, this did not occur with mastication time. The numerical differences between the diseased and nondiseased side in surgical patients tended to be higher than the crosswise differences in controls. CONCLUSION: 4D CT images revealed differences in jaw function between patients who underwent mandibular reconstruction and controls. 4D CT could be used to evaluate postoperative outcomes following mandibular reconstruction.CHURCHILL LIVINGSTONE, 2016, Journal of Cranio-Maxillofacial Surgery, 44(5) (5), 637 - 41, English, International magazine[Refereed]Scientific journal
- The lateral retropharyngeal node (LRPN) is located in the posterior pharynx space which surrounds the internal carotid artery and prevertebral muscle. LRPN is commonly referred to as the Rouviere lymph nodes. LRPN metastasis often occurs from pharyngeal cancer, but seldom occurs from oral cancer. Oral cancers invading the pharynx sometimes metastasize to LRPN, but the prognosis of those with LRPN metastasis is extremely poor because there is no appropriate treatment for LRPN metastasis. We experienced two patients with oral squamous cell carcinoma which had metastasized to LRPN in spite of no remarkable posterior invasion. One of the two patients underwent parapharyngeal dissection, and one has remained disease-free for 7 years. The mechanism of LRPN metastasis of oral cancer without posterior invasion and the usefulness of parapharyngeal dissection are evaluated.一般社団法人 日本口腔腫瘍学会, Mar. 2015, Journal of Japanese Society of Oral Oncology, 27(1) (1), 1 - 6, Japanese
- The purpose of this study was to sequentially evaluate bone union of fibular grafts in mandibular reconstruction. Patients who underwent routine follow-up computed tomography (CT) and panoramic X-ray imaging during a period of >= 2 years were enrolled. On panoramic X-ray images, bone union was scored as 0 (absent callus formation) or 1 (complete callus formation). On CT images, a scale of 0 to 2 was used (0, absent callus formation; 1, complete callus formation only on the labial side; 2, complete callus formation on both the labial and lingual side). A total of 56 bone junctions were evaluated in 20 patients. Five of 56 junctions (9%) in four of 20 patients (20%) showed radiological non-union (panoramic X-ray score = 0, CT score = 0 or 1) at 2 years after surgery. All bone junctions with radiological nonunion were located at the mandibular angle. No categorical values, including diabetes mellitus and radiation therapy, were significantly associated with radiological non-union. In conclusion, assessing at least two sides (i.e. labial and lingual sides) on CT images is adequate to evaluate bone union in transferred fibula flaps. Careful fixation at the mandibular angle may improve the rate of bone union.CHURCHILL LIVINGSTONE, 2015, International Journal of Oral and Maxillofacial Surgery, 44(8) (8), 942 - 947, English, International magazine[Refereed]Scientific journal
- Concurrent chemoradiotherapy with high-dose single-agent cisplatin has been recognized worldwide as the standard treatment for resectable advanced head and neck squamous cell carcinoma with a high risk of recurrence. However, because of severe acute adverse events compared with radiation therapy alone, this regimen is still not widely used in Japan. Hence, we evaluated the feasibility and safety of this regimen in Japanese patients with oral squamous cell carcinoma having high risk factors for recurrence. Microscopically incomplete resection, extracapsular extension, and two or more lymph node metastases were defined as the high-risk factors. The treatment regimen included three cycles of cisplatin at a dose of 100 mg/m(2) and concomitant radiation therapy (66 Gy/33 Fr). Nineteen patients were enrolled. The completion rate with a cumulative cisplatin dose of more than 200 mg/m(2) was 78.9%, and 63.1% with a cumulative cisplatin dose of more than 240 mg/m2. With an average follow-up period for survivors of 15.8 months (range 3-46 months), 24-months LRC, RFS, and OS were 93.8%, 62.2%, and 79.1%, respectively. This cisplatin and concurrent radiation regimen is feasible for Japanese patients with oral squamous cell carcinoma having high-risk factors for postoperative recurrence. (C) 2013 Asian AOMS, ASOMP, JSOP, JSOMS, JSOM, and JAMI. Published by Elsevier Ltd. All rights reserved.*ELSEVIER SCIENCE INC, 2015, Journal of Oral and Maxillofacial Surgery, Medicine, and Pathology, 27(1) (1), 11 - 15, English[Refereed]Scientific journal
- OBJECTIVE: The purpose of this study was to retrospectively investigate the multivariate relationships among the various risk factors for postoperative delirium in patients undergoing oral cancer surgery. MATERIAL AND METHODS: The medical records of all patients with oral cancer who underwent curative head and neck surgery between April 2011 and March 2013 at our institution were retrospectively reviewed. There was a total of 188 patients, including 110 males and 78 females. RESULTS: We found that older age, extensive surgical procedure, longer operation, excessive hemorrhage, blood transfusion, longer postoperative management in the intensive care unit, longer postoperative hospital stay, lower albumin level in the preoperative blood test, and lower total protein, albumi, n and hemoglobin levels and a higher C-reactive protein (CRP) level in the postoperative blood tests were significant variables in the univariate analysis (p < 0.05). We also determined that an older age (odds ratio [OR] = 6.83), intraoperative lower hemoglobin levels (OR = 6.82), and excessive hemorrhage (OR = 3.62) during surgery were significant variables in the multivariate analysis. CONCLUSION: Clinicians should pay special attention to preventing delirium during the postoperative management of older patients with these risk factors. Furthermore, increasing the hemoglobin levels during surgery may be able to prevent postoperative delirium.CHURCHILL LIVINGSTONE, 2015, Journal of Cranio-Maxillofacial Surgery, 43(7) (7), 1094 - 8, English, International magazine[Refereed]Scientific journal
- Spindle cell carcinoma of the oral cavity: The impact of chemotherapy on pulmonary metastatic tumor doubling timeSpindle cell carcinoma (SpCC) an aggressive squamous cell carcinoma, variant, frequently metastasizes to regional lymph nodes and distant organs. Unfortunately, an effective treatment method for oral SpCC distant metastasis has not yet been established. Here we present 2 of oral SpCC cases that showed distant metastases after initial treatment, and 2 that showed distant metastases following during surgery. We calculated the tumor doubling time (TDT) and onset of the pulmonary metastatic and examined the TDT of the pulmonary metastatic tumor in patients with or without chemotherapy to determine the effect of anticancer drugs on oral SpCC. Tumor growth curves revealed that pulmonary metastasis likely grew to 1mm, 122 days before the initial examination, indicating that most oral SpCC patients should be treated for metastases. Three patients underwent chemotherapy for pulmonary metastatic tumor, complete response (CR) in one patient and no change (NC) in two. Thus, SpCC patients may have pulmonary micro-metastases even at the initial examination. We recommend wide resection for oral SpCC patients, followed by chemotherapy to prevent metastases.Kobe University School of Medicine, 2015, Kobe Journal of Medical Sciences, 61(3) (3), E64-70 - E70, English, Domestic magazine[Refereed]Scientific journal
- 日本医療機能評価機構による医療事故情報収集等事業第1〜37回報告書(平成17年4月〜平成26年3月)から狩猟し得た「電気メス・レーザー等を使用した手術に関連するインシデント事例」86件を対象に、使用された医療機器の内訳、患者への影響、原因について調査した。結果、使用された医療機器は、「電気メス」61件(71%)、「サージビームや消化管内視鏡などの光源」11件(13%)、「ラジオ波焼灼治療機器」7件(8%)、「レーザー」5件(6%)、「超音波凝固切開装置」2件(2%)であった。患者への影響は、「熱傷」46件(53%)、「異物残存」8件(9%)、「近接組織(臓器)の損傷」6件(7%)、「穿孔」3件(3%)、「その他」5件(6%)、「影響なし」18件(21%)であった。原因は、「使用方法の誤り」33件(38%)、「機器の不具合・破損」20件(23%)、「突然の発火」17件(20%)、「対極板の使用に関連したもの」9件(10%)、「その他」7件(8%)であった。患者への影響・原因のうち比較的多くみられた以下のケースについて改善策を中心に考察(一社)日本レーザー歯学会, Dec. 2014, 日本レーザー歯学会誌, 25(3) (3), 136 - 139, Japanese
- Sequential changes in oral dryness evaluated by a moisture-checking device in patients with oropharyngeal cancer during chemoradiotherapy: a pilot study.PURPOSE: Although oral dryness is a predictor for oral mucositis caused by Chemoradiotherapy (CRT) for head and neck cancer, there have been few reports evaluating the sequential changes in oral dryness during therapy. Studies have determined the reliability and usefulness of a moisture-checking device for the evaluation of dry mouth. This study aimed to evaluate the oral moisture level in patients with Oropharyngeal Cancer (OPC) during CRT using a moisture-checking device. METHODS: Oral moisture level was measured with an oral moisture-checking device (Moisture Checker Mucus®) at the lingual and buccal mucosa before, at the midpoint, and at the end of CRT in patients with OPC. Sequential changes in oral dryness were evaluated. RESULTS: A significant decrease in oral moisture level at the lingual mucosa was found when comparing values before and at the end of CRT (P=0.017). Decreases in oral moisture level at the buccal mucosa were not significant. CONCLUSIONS: A moisture-checking device is considered a useful tool for determining the sequential changes in oral dryness during CRT for head and neck cancer. Our findings provide a basis for future larger long-term studies of oral moisture levels in OPC patients receiving CRT.Jun. 2014, Oral health and dental management, 13(2) (2), 507 - 11, English, International magazine[Refereed]Scientific journal
- 2014, Oral Science in Japan, 49 - 50, EnglishClinical study of implant treatment for diabetic patientsScientific journal
- BACKGROUND: To maintain normal function, the lymphatic endothelium is regulated by cell-cell junctions. There have been few studies of lymphatic endothelial cell junctions using standard cell biological methods. This study had two purposes: to characterize cell junctions in cultured lymphatic endothelial cells and to investigate the effects of the inflammatory cytokine TNF-α on altered cell-cell junctions. METHODS AND RESULTS: Cultured human dermal lymphatic endothelial cells (HDLEC) were immunostained with the tight junction marker, ZO-1, and adherens junction markers, VE-cadherin and PECAM-1. In TNF-α-treated HDLEC, we evaluated changes in endothelial cell junctions by immunostaining and through the use of transendothelial electrical resistance (TER). Immunofluorescence staining of HDLEC revealed heterogeneity among the endothelial cell junctions, which could be classified into continuous and discontinuous junctions. In these cell junctions, ZO-1 and VE-cadherin were co-localized. Double immunofluorescence staining revealed the broad distribution of VE-cadherin at the cell periphery, where VE-cadherin and PECAM-1 were co-localized. TNF-α treatment decreased TER, caused a predominance in the appearance of discontinuous junctions with a reduction in the broad distribution of VE-cadherin at the cell periphery in HDLEC. CONCLUSIONS: The results indicate a heterogeneous distribution of cell junctions in HDLEC involving continuous and discontinuous junctions. Our data also suggest that TNF-α alters the normal distribution of cell junctions and affects the endothelial barrier of cultured lymphatic endothelial cells. The broad distribution of VE-cadherin at the cell periphery may reflect the lymphatic permeability.Lead, MARY ANN LIEBERT, INC, 2014, Lymphatic Research and Biology, 12(3) (3), 136 - 43, English, International magazine[Refereed]Scientific journal
- PURPOSE: The aim of this study was to evaluate the usefulness of covering open wounds with a polyglycolic acid (PGA) sheet and a fibrin glue spray after partial glossectomy. MATERIALS AND METHODS: We clinically evaluated postoperative pain and scar contracture in 44 patients who underwent partial glossectomy followed by covering with a PGA sheet and a fibrin glue spray (PGA sheet group), as compared with 29 patients who were closed primarily (primary closure group). RESULTS: Duration of nonsteroidal anti-inflammatory drugs was almost the same between the PGA sheet group and the primary closure group. The degree of scar contracture was mild in many cases in both groups. In the case in which the excision area was wide and depth was shallow, there was a tendency for the scar contracture to be less in the PGA sheet group. CONCLUSIONS: Our findings showed that the use of a PGA sheet and fibrin glue spray for open wounds resulting from partial glossectomy was useful in terms of rapid relief from postoperative pain and prevention of scar contracture.W B SAUNDERS CO-ELSEVIER INC, 2013, Journal of Oral and Maxillofacial Surgery, 71(2) (2), e126-31 - E131, English, International magazine[Refereed]Scientific journal
- In this study we investigated the relationships among the risk factors for inferior alveolar nerve injury (IANI), and the difference between preoperative imaging findings on panoramic radiographs and computed tomography (CT), by univariate and multivariate analyses. We determined the following to be significant variables by multivariate analysis: panoramic radiographic signs, such as the loss of the white line of the inferior alveolar canal or the diversion of the canal; excessive haemorrhage during extraction; and a close relationship of the roots to the IAN (type 1 cases) on CT examination. CT findings of type 1 were associated with a significantly higher risk (odds ratio 43.77) of IANI. In addition, many panoramic findings were not consistent with CT findings (275 of 440 teeth; 62.5%). These results suggest that CT findings may be able to predict the development of IANI more accurately than panoramic findings. Panoramic radiography alone did not provide sufficiently reliable images required for predicting IANI. Therefore, when the panoramic image is suggestive of a close relationship between the impacted tooth and the IAN, CT should be recommended as a means of conducting further investigations.CHURCHILL LIVINGSTONE, 2013, International Journal of Oral and Maxillofacial Surgery, 42(7) (7), 843 - 851, English, International magazine[Refereed]Scientific journal
- OBJECTIVES: Secondary malignancy in the oral mucosa is recognized as one of the most serious complications in patients who received allogenic hematopoietic stem cell transplantation (HSCT). However, potential risk factors associated with carcinogenesis after HSCT that have been reported remain elusive. We experienced a rare case of secondary malignancies of the oral and esophageal mucosa and analyzed the expression of tumor suppressor gene product p16. CASE REPORT: A 35-year-old male had malignant lesions of the oral and esophageal mucosa two years after HSCT. Partial maxillectomy and endoscopic submucosal dissection were performed. Immunohistochemical analyses revealed that the tumor cells of malignant and premalignant lesions of the oral cavity and esophagus but not keratosis were positive for p16. CONCLUSIONS: Pathological examinations with p16 immunohistochemistry may contribute to an early diagnosis of secondary malignancy after HSCT.Lead, BMC, 2012, Head and Neck Oncology, 4(1) (1), 38 - 38, English, International magazine[Refereed]Scientific journal
- 白板症や早期舌癌で舌部分切除術が行われた68例(男性35例、女性33例、平均61.7歳)を対象に、術後開放創にコラーゲン使用人工皮膚貼付の31例(コラーゲン群)と、フィブリン糊でポリグリコール酸(PGA)シート貼付の37例(PGA群)に分け、その効果について比較した。病理診断は異型上皮・上皮内癌28例、扁平上皮癌40例、平均切除面積はコラーゲン群:837.3mm2、PGA群:736.0mm2、術後鎮痛剤服用平均日数はコラーゲン群:7.2日、PGA群:5.9日であり、PGAシート付着最終確認日は平均15.4日であった。コラーゲン群とPGA群の瘢痕拘縮の程度は、「なし」がそれぞれ5例、13例、「軽度」が16例、23例、「中等度」が10例、1例、「高度」は両群とも0例であった。なお、術後の栄養摂取はコラーゲン群が1週間、PGA群が2日間経鼻チューブを使用した。舌部分切除後のフィブリン糊とPGAシート使用は早期摂食、疼痛緩和、瘢痕拘縮予防に有用と考えられた。日本口腔外科学会, Jul. 2011, Japanese journal of oral and maxillofacial surgery, 57(7) (7), 394 - 400, Japanese[Refereed]
- (株)デンタルダイヤモンド社, Dec. 2024, DENTAL DIAMOND, 49(16) (16), 19 - 20, JapaneseDd診断力てすと 右下顎臼歯部の腫瘤
- (公社)日本新生児成育医学会, Oct. 2024, 日本新生児成育医学会雑誌, 36(3) (3), 467 - 467, Japanese無症候性先天性サイトメガロウイルス感染症の対応を考える 先天性CMV感染児の遅発性難聴を対象としたバルガンシクロビルの医師主導治験について
- (NPO)日本口腔科学会, Sep. 2024, 日本口腔科学会雑誌, 73(2) (2), 113 - 113, Japaneseヒト下歯槽神経のバリア制御に関連する分子の解析
- (NPO)日本口腔科学会, Sep. 2024, 日本口腔科学会雑誌, 73(2) (2), 216 - 216, Japanese歯の喪失は65歳高齢者の早期要介護発生リスクと関係するか?
- (一社)日本糖尿病学会, Apr. 2024, 糖尿病, 67(Suppl.1) (Suppl.1), S - 220, Japaneseインスリン抵抗性を伴う難治性糖尿病に対するエンパグリフロジンの有効性・安全性に関する多施設共同非盲検単群試験(EMPIRE)
- (公社)日本皮膚科学会, Feb. 2024, 日本皮膚科学会雑誌, 134(2) (2), 330 - 331, Japanese臨床研究と医療倫理
- (一社)日本臨床薬理学会, Jan. 2024, 日本臨床薬理学会学術総会抄録集, 44回, 1 - 3, Japanese多施設共同臨床研究において多職種で取り組んだ品質管理活動 データマネージャーの視点より
- (公社)日本口腔インプラント学会, Dec. 2023, 日本口腔インプラント学会誌, 36(4) (4), E206 - E207, Japanese下顎歯肉癌腓骨皮弁再建症例におけるインプラント支持型圧迫床を用いた前庭拡張術の工夫
- (公社)日本顎顔面インプラント学会, Nov. 2023, Japanese Journal of Maxillo Facial Implants, 22(3) (3), 242 - 242, Japanese当科における口腔癌癌患者の下顎の広範囲顎骨支持型装置に際し口腔前庭拡張術を要した11例
- (一社)日本小児感染症学会, Nov. 2023, 日本小児感染症学会総会・学術集会プログラム・抄録集, 55回, 212 - 212, Japanese先天性サイトメガロウイルス感染症治療例における血漿サイトメガロウイルスDNA定量の意義と中央診断体制の構築
- (NPO)日本口腔科学会, Jul. 2023, 日本口腔科学会雑誌, 72(2) (2), 166 - 166, Japanese経皮的炭酸ガスペーストによるラット筋損傷モデルにおける瘢痕化防止と筋再生促進効果
- (一社)日本口腔感染症学会, May 2023, 日本口腔感染症学会雑誌, 30(1) (1), 60 - 60, Japaneseダプトマイシンの長期投与が奏功したMRSA感染を伴う放射線性下顎骨骨髄炎の1例
- (公社)日本小児科学会, Feb. 2023, 日本小児科学会雑誌, 127(2) (2), 190 - 190, Japanese生後2ヵ月以内の症候性先天性サイトメガロウイルス感染症児を対象とした経口バルガンシクロビル治療 医師主導治験の結果
- 2023, 日本口腔腫瘍学会総会・学術大会プログラム・抄録集, 41stFactors associated with treatment outcomes and pathological features in patients with osteoradionecrosis
- (公社)日本顎顔面インプラント学会, Nov. 2022, Japanese Journal of Maxillo Facial Implants, 21(3) (3), 237 - 237, Japanese当科における口腔癌患者の広範囲顎骨支持型装置の成功率に関する後ろ向き観察研究
- (NPO)日本口腔科学会, Jul. 2022, 日本口腔科学会雑誌, 71(2) (2), 91 - 91, Japanese緩和照射に関する臨床的検討
- (NPO)日本口腔科学会, Jul. 2022, 日本口腔科学会雑誌, 71(2) (2), 110 - 110, Japanese局所的炭酸ガス投与による口腔扁平上皮癌の腫瘍免疫抑制に対する改善効果
- 2022, 日本口腔腫瘍学会総会・学術大会プログラム・抄録集, 40thA study of patients who needed to apply for nursing insurance during hospitalization for oral cancer
- わが国における臨床研究環境は近年著しく変化している。なかでも2018年4月1日に臨床研究法が施行されたことは大きな転換点といえる。その背景として2013年から2014年にかけて、ディオバン事件を代表とする臨床研究に関する不適切な事案が複数生じたことが挙げられる。それらの臨床研究では、複数の大学機関が関連していたデータ操作・不透明な奨学寄附金を通じた研究者と製薬企業との関係性が大きくクローズアップされ、社会問題化した。これらの研究不正に鑑みて、厚労省は、臨床研究の信頼の回復のためには法規制が必要との結論に達し、倫理指針の改定・厳格化を経て臨床研究法施行の運びとなった。臨床研究に関わる全てのものにとって本法の要請を理解し、適切に対応することが求められている一方で、本法を理解するための文書類の多さや手続きの煩雑さなど、研究者の負担が大きく増えたことから、臨床試験の停滞や萎縮を招いている。本法の大きな特徴として、研究責任医師に臨床研究の責任が集約されたこと、研究者は厚労省が認定した認定臨床研究審査委員会を通して試験計画を厚労省に届けること、利益相反の流れが詳細に定められたことなどが挙げられる。本報告では臨床研究倫理における臨床研究法成立までの臨床研究環境の変化について述べたうえで、臨床研究法について概説する。(著者抄録)(一社)日本口腔腫瘍学会, Dec. 2021, 日本口腔腫瘍学会誌, 33(4) (4), 159 - 163, Japanese
- (一社)日本小児感染症学会, Oct. 2021, 日本小児感染症学会総会・学術集会プログラム・抄録集, 53回, 122 - 122, Japanese症候性先天性サイトメガロウイルス感染症を対象とした抗ウイルス薬治療の医師主導治験の進捗
- 2021, 日本口腔腫瘍学会総会・学術大会プログラム・抄録集, 39thEffect of percutaneous administration of carbon dioxide to improve tumor immunosuppression
- 2021, 日本口腔腫瘍学会総会・学術大会プログラム・抄録集, 39thConsideration of non-survival cases in patients with oral squamous cell carcinoma and Future perspectives in a tertiary referral center
- (一社)日本口腔ケア学会, Sep. 2020, 日本口腔ケア学会雑誌, 14(3) (3), 53 - 54, Japanese口腔ケアのエビデンスを検証するためにはどのような研究をすればよいのか アカデミア臨床研究環境のこれまで 臨床研究法施行の背景
- (NPO)日本口腔科学会, Sep. 2020, 日本口腔科学会雑誌, 69(3) (3), 248 - 248, Japanese舌に生じた腺扁平上皮癌の1例
- (一社)日本頭頸部癌学会, Jul. 2020, 頭頸部癌, 46(2) (2), 183 - 183, Japanese口腔癌cN(+)における根治的頸部郭清範囲の検討
- (NPO)日本口腔科学会, Jul. 2020, 日本口腔科学会雑誌, 69(2) (2), 153 - 153, Japanese当科で歯科介入を行った高用量骨吸収抑制薬使用患者におけるMRONJ発症とリスク因子についての検討
- (NPO)日本口腔科学会, Jul. 2020, 日本口腔科学会雑誌, 69(2) (2), 174 - 174, Japanese当科における口腔癌患者における放射線性顎骨壊死に関する臨床的検討
- 2019, 日本口腔腫瘍学会総会・学術大会プログラム・抄録集, 37th, 148, Japanese当科におけるメトトレキサート関連リンパ増殖性疾患の3例
- 2019, 日本口腔腫瘍学会総会・学術大会プログラム・抄録集, 37th, 122, Japanese当科におけるUnusualな再発症例について
- 2019, 日本口腔腫瘍学会総会・学術大会プログラム・抄録集, 37th, 120, Japanese炭酸ガスを使用した効率的な低酸素環境改善による口腔癌の新規治療法の開発と治療抵抗性の改善効果
- 2019, 日本口腔腫瘍学会総会・学術大会プログラム・抄録集, 37th, 112, Japanese再建を伴う口腔癌の周術期静脈血栓塞栓症について
- 2019, 日本口腔腫瘍学会総会・学術大会プログラム・抄録集, 37th, 156, Japanese口腔癌におけるPET‐MRI~第二報~
- (公社)日本顎顔面インプラント学会, Nov. 2018, Japanese Journal of Maxillo Facial Implants, 17(3) (3), 224 - 224, Japanese当科におけるインプラント埋入症例と喪失リスク因子に関する後ろ向き観察研究
- (公社)日本診療放射線技師会, Sep. 2018, JART: 日本診療放射線技師会誌, 65(9) (9), 1011 - 1011, JapaneseFour-dimensional CT(4DCT)による咀嚼時の下顎頭前方滑走の解析
- (一社)日本外傷歯学会, Jul. 2018, 日本外傷歯学会総会・学術大会プログラム・抄録集, 18回, 48 - 48, Japanese当院における過去10年間の外傷歯症例の臨床的検討―世代別の特徴に関する分析―
- (NPO)日本口腔科学会, Jul. 2018, 日本口腔科学会雑誌, 67(2) (2), 117 - 117, Japanese頸部郭清を伴う口腔癌術後合併症に関する臨床的検討
- (NPO)日本口腔科学会, Jul. 2018, 日本口腔科学会雑誌, 67(2) (2), 103 - 103, Japanese頸部リンパ節転移陽性口腔扁平上皮癌の予後因子におけるlymph node ratioの有用性に関する検討
- (NPO)日本口腔科学会, Jul. 2018, 日本口腔科学会雑誌, 67(2) (2), 121 - 121, Japanese膠原病を有する口腔癌症例の臨床的検討
- (NPO)日本口腔科学会, Jul. 2018, 日本口腔科学会雑誌, 67(2) (2), 112 - 112, Japanese当科における口腔癌への緩和照射に関する臨床的検討
- (NPO)日本口腔科学会, Jul. 2018, 日本口腔科学会雑誌, 67(2) (2), 175 - 175, Japanese当科における矯正用アンカープレートの臨床統計学的検討
- (NPO)日本口腔科学会, Jul. 2018, 日本口腔科学会雑誌, 67(2) (2), 113 - 113, Japanese術後に気道閉塞を生じた口腔癌患者の3例
- (NPO)日本口腔科学会, Jul. 2018, 日本口腔科学会雑誌, 67(2) (2), 110 - 110, Japanese口腔癌術後に予定外に再度の全身麻酔による手術を要した症例の検討
- (NPO)日本口腔科学会, Jul. 2018, 日本口腔科学会雑誌, 67(2) (2), 119 - 119, Japanese口腔癌原発巣手術における術中迅速診断の臨床的検討
- 09 May 2018, 頭頸部癌, 44(2) (2), 140, Japanese口腔癌cN1症例に関する頸部郭清術の郭清範囲についての検討
- (一社)日本頭頸部癌学会, May 2018, 頭頸部癌, 44(2) (2), 140 - 140, Japanese口腔癌cN1症例に関する頸部郭清術の郭清範囲についての検討
- 2018, 日本口腔科学会雑誌(Web), 67(2) (2), 117(J‐STAGE), Japanese頸部郭清を伴う口腔癌術後合併症に関する臨床的検討
- 2018, 日本口腔科学会雑誌(Web), 67(2) (2), 103(J‐STAGE), Japanese頸部リンパ節転移陽性口腔扁平上皮癌の予後因子におけるlymph node ratioの有用性に関する検討
- 2018, 日本口腔科学会雑誌(Web), 67(2) (2), 121(J‐STAGE), Japanese膠原病を有する口腔癌症例の臨床的検討
- 2018, 日本口腔腫瘍学会総会・学術大会プログラム・抄録集, 36th, 161, Japanese放射線性下顎骨壊死の診断におけるfollow up PET‐CTの有用性
- 2018, 日本口腔腫瘍学会総会・学術大会プログラム・抄録集, 36th, 181, Japanese皮弁再建後の再発舌癌に対して救済手術を施行した2例
- 2018, 日本口腔科学会雑誌(Web), 67(2) (2), 112(J‐STAGE), Japanese当科における口腔癌への緩和照射に関する臨床的検討
- 2018, 日本口腔科学会雑誌(Web), 67(2) (2), 175(J‐STAGE), Japanese当科における矯正用アンカープレートの臨床統計学的検討
- 2018, 日本口腔腫瘍学会総会・学術大会プログラム・抄録集, 36th, 160, Japanese超音波断層法による口腔癌頸部リンパ節転移の検討
- 2018, 日本口腔腫瘍学会総会・学術大会プログラム・抄録集, 36th, 164, Japanese舌扁平上皮癌の原発巣再発例の検討
- 2018, 日本口腔科学会雑誌(Web), 67(2) (2), 113(J‐STAGE), Japanese術後に気道閉塞を生じた口腔癌患者の3例
- 2018, 日本口腔腫瘍学会総会・学術大会プログラム・抄録集, 36th, 151, Japanese口腔癌術後病理minor risk症例の臨床的検討
- 2018, 日本口腔科学会雑誌(Web), 67(2) (2), 110(J‐STAGE), Japanese口腔癌術後に予定外に再度の全身麻酔による手術を要した症例の検討
- 2018, 日本口腔腫瘍学会総会・学術大会プログラム・抄録集, 36th, 149, Japanese口腔癌再建術後Recipient‐site infectionの定義に関する文献レビュー
- 2018, 日本口腔科学会雑誌(Web), 67(2) (2), 119(J‐STAGE), Japanese口腔癌原発巣手術における術中迅速診断の臨床的検討
- 2018, 日本口腔腫瘍学会総会・学術大会プログラム・抄録集, 36th, 160, Japanese口腔癌におけるPET/MRIの可能性について
- (一社)日本レーザー歯学会, Dec. 2017, 日本レーザー歯学会誌, 28(2-3) (2-3), 45 - 46, Japanese
- (一社)日本レーザー歯学会, Dec. 2017, 日本レーザー歯学会誌, 28(2-3) (2-3), 50 - 51, Japanese
- (一社)日本顎顔面補綴学会, Dec. 2017, 顎顔面補綴, 40(2) (2), 55 - 55, Japanese上顎部分切除後の顎義歯装着に関する皮弁再建・非再建群の比較
- (公社)日本顎顔面インプラント学会, Nov. 2017, Japanese Journal of Maxillo Facial Implants, 16(3) (3), 233 - 233, Japanese移植腓骨へ埋入したインプラント体の周囲炎に対し炭酸ガスレーザーを適用した1例
- (公社)日本診療放射線技師会, Sep. 2017, 日本診療放射線技師会誌, 64(9) (9), 1220 - 1220, JapaneseCBCTを用いた実物大臓器立体モデル作製の基礎検討
- (NPO)日本口腔科学会, Jul. 2017, 日本口腔科学会雑誌, 66(2) (2), 113 - 113, Japanese当科における予防的頸部郭清術に関する後ろ向き検討
- (NPO)日本口腔科学会, Jul. 2017, 日本口腔科学会雑誌, 66(2) (2), 114 - 114, Japanese口腔扁平上皮癌における術後早期(1年以内)の予後不良例に関する臨床的検討
- (NPO)日本口腔科学会, Jul. 2017, 日本口腔科学会雑誌, 66(2) (2), 114 - 114, Japanese口腔癌手術における嚥下改善手術に関する臨床的検討
- (一社)日本顎関節学会, Jul. 2017, 日本顎関節学会雑誌, 29(Suppl.) (Suppl.), 92 - 92, Japanese4DCTによる咀嚼時の下顎頭前方滑走の解析
- (一社)日本口腔ケア学会, Apr. 2017, 日本口腔ケア学会雑誌, 11(3) (3), 121 - 121, Japanese頭頸部癌化学放射線治療患者における口腔内細菌数と口腔粘膜水分量の解析
- 2017, 日本口腔科学会学術集会プログラム・抄録集, 71st, 181, Japanese当科における予防的頸部郭清術に関する後ろ向き検討
- 2017, 日本レーザー歯学会総会・学術大会プログラム・講演抄録集, 29th, 45, Japanese口腔扁平上皮癌細胞に与えるLED光照射の影響
- 2017, 日本口腔科学会学術集会プログラム・抄録集, 71st, 183, Japanese口腔扁平上皮癌における術後早期(1年以内)の予後不良例に関する臨床的検討
- 2017, 日本レーザー歯学会総会・学術大会プログラム・講演抄録集, 29th, 36, Japanese口腔白板症に対する炭酸ガスレーザー蒸散術後の残存および再発に関する臨床的検討
- 2017, 日本口腔科学会学術集会プログラム・抄録集, 71st, 183, Japanese口腔癌手術における嚥下改善手術に関する臨床的検討
- (一社)日本レーザー歯学会, Dec. 2016, 日本レーザー歯学会誌, 27(3) (3), 148 - 149, Japanese
- (公社)日本顎顔面インプラント学会, Nov. 2016, Japanese Journal of Maxillo Facial Implants, 15(3) (3), 207 - 207, Japanese内視鏡支援下で上顎洞迷入インプラントの摘出後に骨造成術を行った1例
- (NPO)日本口腔科学会, Jul. 2016, 日本口腔科学会雑誌, 65(2) (2), 127 - 128, Japanese当科におけるFibro-osseous lesionsの臨床的検討
- (NPO)日本口腔科学会, Jul. 2016, 日本口腔科学会雑誌, 65(2) (2), 214 - 214, Japanese遺伝子解析により確定診断を得た頬粘膜MALTリンパ腫の1例
- (一社)日本外傷歯学会, Jul. 2016, 日本外傷歯学会総会・学術大会プログラム・抄録集, 16回, 29 - 29, Japanese当院における過去8年間の外傷歯患者の臨床統計的検討~顎骨骨折の有無と外傷歯の関係について~
- (一社)日本外傷歯学会, Jul. 2016, 日本外傷歯学会総会・学術大会プログラム・抄録集, 16回, 30 - 30, Japanese全身麻酔挿管中に生じる歯牙損傷の後ろ向き調査
- (一社)日本顎関節学会, Jul. 2016, 日本顎関節学会雑誌, 28(Suppl.) (Suppl.), 130 - 130, Japanese当科における顎関節症脱臼の臨床的検討
- 2016, 日本口腔科学会学術集会プログラム・抄録集, 70th, 159, Japanese当科におけるFibro‐osseous lesionsの臨床的検討
- 2016, 日本レーザー歯学会総会・学術大会プログラム・講演抄録集, 28th, 33, Japanese小帯付着異常に対する炭酸ガスレーザー治療の臨床的検討
- 2016, 日本口腔腫瘍学会総会・学術大会プログラム・抄録集, 34th, 231, Japanese術前18F‐FDG PET/CT撮影での口腔癌原発巣における定量評価の有用性
- 2016, 日本口腔腫瘍学会総会・学術大会プログラム・抄録集, 34th, 234, Japanese口腔扁平上皮癌被膜外浸潤症例の臨床病理学的検討
- 2016, 日本口腔腫瘍学会総会・学術大会プログラム・抄録集, 34th, 221, Japanese口腔扁平上皮癌患者の遠位レベル(Level4,5)への頸部リンパ節転移が予後に与える影響
- 2016, 日本口腔腫瘍学会総会・学術大会プログラム・抄録集, 34th, 208, Japanese局所的炭酸ガス投与による皮弁壊死抑制効果
- 2016, 日本口腔科学会学術集会プログラム・抄録集, 70th, 286, Japanese遺伝子解析により確定診断を得た頬粘膜MALTリンパ腫の1例
- 2016, 日本口腔腫瘍学会総会・学術大会プログラム・抄録集, 34th, 208, Japanese移植腓骨と下顎骨の癒合における骨膜温存の重要性
- (公社)日本口腔インプラント学会, Dec. 2015, 日本口腔インプラント学会誌, 28(4) (4), 564 - 565, Japanese糖尿病患者に対するインプラント治療の経験
- (公社)日本口腔インプラント学会, Dec. 2015, 日本口腔インプラント学会誌, 28(4) (4), 559 - 560, Japanese矯正治療と骨造成術を併用しインプラント治療を行った長期観察の1例
- (公社)日本顎顔面インプラント学会, Nov. 2015, Japanese Journal of Maxillo Facial Implants, 14(3) (3), 248 - 248, Japanese交通外傷後の上顎前歯骨欠損部に骨造成と再度のインプラント治療を行った1例
- (一社)日本レーザー歯学会, Aug. 2015, 日本レーザー歯学会誌, 26(2) (2), 89 - 90, Japanese
- Japanese Stomatological Society, 2015, Oral science in Japan, 79 - 82, EnglishClinical analysis of the chronological change in bone mass following sinus floor elevation
- 2015, 日本口腔腫瘍学会総会・学術大会プログラム・抄録集, 33rd, 295, Japanese当科における頸部郭清術術後の頸部ドレーンに関する臨床的検討
- 2015, 日本口腔腫瘍学会総会・学術大会プログラム・抄録集, 33rd, 237, Japanese当科における放射線性顎骨壊死に関する臨床的検討
- 2015, 日本口腔腫瘍学会総会・学術大会プログラム・抄録集, 33rd, 301, Japanese当科における口腔扁平上皮癌遠隔転移例の臨床的検討とリスク因子について
- 2015, 日本口腔腫瘍学会総会・学術大会プログラム・抄録集, 33rd, 188, Japanese口腔癌原発巣におけるDual‐time‐point FDG PETの有用性に関する検討
- 2015, 日本レーザー歯学会総会・学術大会プログラム・講演抄録集, 27th, 32, JapaneseCO2レーザーによる舌早期癌に対する舌部分切除術に関する検討
- 25 Nov. 2014, Japanese Journal of Maxillo Facial Implants, 13(3) (3), 143, Japanese上顎洞底拳上術後の上顎洞粘膜肥厚の経時的変化に関する検討
- (公社)日本顎顔面インプラント学会, Nov. 2014, Japanese Journal of Maxillo Facial Implants, 13(3) (3), 143 - 143, Japanese上顎洞底挙上術後の上顎洞粘膜肥厚の経時的変化に関する検討
- (一社)日本頭頸部癌学会, May 2014, 頭頸部癌, 40(2) (2), 229 - 229, Japanese口腔癌cN1症例に対する頸部郭清術の郭清範囲についての検討
- Japanese Stomatological Society, 2014, Oral Science in Japan, 79 - 81, EnglishSuccessive macroglossia after toxic epidermal necrolysisIntroduction scientific journal
- Japanese Stomatological Society, 2014, Oral Science in Japan, 69 - 71, EnglishClinical experience with the application of polyglycolic acid sheets and fibrin glue spray after resection of buccal mucosal lesions: A pilot studyIntroduction scientific journal
- 2014, 日本口腔腫瘍学会総会・学術大会プログラム・抄録集, 32nd, 172, Japanese口腔癌cN1症例に対する頸部郭清術の郭清範囲についての検討
- 2014, 日本口腔腫瘍学会総会・学術大会プログラム・抄録集, 32nd, 219, Japanese40歳未満に発生した舌扁平上皮癌21例の検討
- (公社)日本顎顔面インプラント学会, Nov. 2013, Japanese Journal of Maxillo Facial Implants, 12(3) (3), 111 - 111, Japanese片側性唇顎口蓋裂を伴う咬合不全に対して腓骨皮弁による骨再建とインプラント埋入術を行った成人男性の1例
- (NPO)日本顎変形症学会, May 2013, 日本顎変形症学会雑誌, 23(2) (2), 174 - 174, Japanese外科的矯正治療により咬合改善を得た上下顎の歯数不調和を伴う下顎骨骨折変形治癒症例
- (一社)日本レーザー歯学会, Apr. 2013, 日本レーザー歯学会誌, 24(1) (1), 28 - 29, Japanese
- 2013, 日本口腔腫瘍学会総会・学術大会プログラム・抄録集, 31st, 124, Japanese当科における舌部分切除術
- 2013, 日本口腔腫瘍学会総会・学術大会プログラム・抄録集, 31st, 140, Japanese舌癌180例のリンパ節転移に関する検討~健側転移について~
- 2013, 日本口腔腫瘍学会総会・学術大会プログラム・抄録集, 31st, 141, Japanese口腔扁平上皮癌術後局所再発症例に関する検討
- 2013, 日本口腔腫瘍学会総会・学術大会プログラム・抄録集, 31st, 144, Japanese口腔扁平上皮癌T4症例に対する手術療法の治療成績
- (一社)日本障害者歯科学会, Sep. 2012, 障害者歯科, 33(3) (3), 448 - 448, Japanese当科にて口腔衛生管理を継続した劣性栄養障害型先天性表皮水疱症患者の1例
- 2012, 日本レーザー歯学会総会・学術大会プログラム・講演抄録集, 24th, 39, Japanese炭酸ガスレーザーによる舌部分切除術におけるポリグリコール酸シートおよびフィブリン糊スプレーの臨床的検討
- 2012, 日本口腔腫瘍学会総会・学術大会プログラム・抄録集, 30th, 211, Japanese骨髄移植後GVHD患者に発生した口腔扁平上皮癌の2例
- (NPO)日本口腔科学会, Jan. 2012, 日本口腔科学会雑誌, 61(1) (1), 193 - 194, Japanese頬粘膜切除後の開放創に対するポリグリコール酸シートおよびフィブリン糊スプレーの使用経験
- (一社)日本外傷歯学会, Nov. 2011, 日本外傷歯学会総会・学術大会プログラム・抄録集, 11回, 24 - 24, Japanese神戸大学医学部附属病院歯科口腔外科における口腔顔面外傷および外傷歯の臨床統計的検討
- (公社)日本顎顔面インプラント学会, Nov. 2011, Japanese Journal of Maxillo Facial Implants, 10(3) (3), 130 - 130, Japanese当科におけるインプラント治療を行った外傷症例の臨床的検討
- (一社)日本口腔衛生学会, Oct. 2011, 口腔衛生学会雑誌, 61(5) (5), 595 - 595, Japanese岐阜県版「歯周病セルフチェック票」とCPIの関係
- (公社)日本口腔外科学会, Sep. 2011, 日本口腔外科学会雑誌, 57(Suppl.) (Suppl.), 200 - 200, Japanese当科における下顎歯肉癌の臨床的検討
- (公社)日本口腔外科学会, Sep. 2011, 日本口腔外科学会雑誌, 57(Suppl.) (Suppl.), 200 - 200, Japanese当科における口底扁平上皮癌手術症例の臨床病理学的検討
- (NPO)日本顎変形症学会, May 2011, 日本顎変形症学会雑誌, 21(2) (2), 154 - 154, Japanese下顎枝垂直骨切り術術後の下顎骨動態に関する検討
- (一社)日本頭頸部癌学会, May 2011, 頭頸部癌, 37(2) (2), 294 - 294, Japanese口腔外科手術時の開放創に対するネオベールおよびボルヒールの使用経験
- (一社)日本レーザー歯学会, Apr. 2011, 日本レーザー歯学会誌, 22(1) (1), 43 - 43, Japanese炭酸ガスレーザーを用いた舌部分切除術におけるネオベールシートおよびボルヒールとテルダーミスとの比較
- 日本学術振興会, 科学研究費助成事業, 基盤研究(C), 神戸大学, 01 Apr. 2025 - 31 Mar. 2028EGFR抵抗性口腔癌におけるYAP阻害剤とナノ粒子の有効性に関する研究
- 日本学術振興会, 科学研究費助成事業, 基盤研究(C), 神戸大学, 01 Apr. 2023 - 31 Mar. 2026好中球に着眼したシェーグレン症候群の新規病理分類提案と治療薬探索
- 日本学術振興会, 科学研究費助成事業, 基盤研究(C), 神戸大学, 01 Apr. 2023 - 31 Mar. 2026顎骨壊死に対する腐骨分離促進療法の探索
- 日本学術振興会, 科学研究費助成事業 若手研究, 若手研究, 神戸大学, 01 Apr. 2020 - 31 Mar. 2024口腔癌における金属ナノ粒子と分子標的薬併用治療の有効性に関する研究
近年、放射線治療効果を高める方法の一つに放射線治療用増感剤として金ナノ粒子を始めとしたメタルナノ粒子が注目を浴びている。ナノ粒子を体内に入れる際、粒子径を100nm以下にすると体循環中へと肝臓の細網内皮系に捕捉されずに循環することが可能である。金ナノ粒子はサイズの調節が容易で粒子表面に化学物質を化学修飾しやすい、イメージングの応用もしやすい特徴がある。現在、口腔癌をはじめとした頭頸部癌領域ではシスプラチンなどの抗癌剤のみならず、抗EGFR抗体や抗PD-1などの分子標的治療薬も臨床応用されている。これらの分子標的薬を金ナノ粒子表面に化学修飾することで選択的に腫瘍細胞へと金ナノ粒子を遊走させることで腫瘍選択的に放射線増感作用が得られる可能性がある。 本年度は、金ナノ粒子とEGFR阻害薬が放射線による増感効果があることを示した。具体的には金ナノ粒子およびEGFR阻害薬がナノ粒子表面で結合していることをラマン分光による測定で確認した。またTEMによりEGFR阻害薬を加えても細胞内に金ナノ粒子が取り込まれることを確認した。また金ナノ粒子、EGFR阻害薬放射線照射の有無で細胞の移動活性、細胞数の変化、細胞増殖能、アポトーシスの変化を解析した。そこで金ナノ粒子が放射線増感効果だけでなく、EGFR阻害薬に対しても相乗効果を示した。以上の結果をGold Nanoparticles Enhance EGFR Inhibition and Irradiation Effects in Head and Neck Squamous Carcinoma CellsというタイトルでBiomed Research international(doi: 10.1155/2020/1281645.)という英文誌に投稿し掲載された。 - Japan Society for the Promotion of Science, Grants-in-Aid for Scientific Research Grant-in-Aid for Challenging Research (Exploratory), Grant-in-Aid for Challenging Research (Exploratory), Kobe University, 09 Jul. 2021 - 31 Mar. 2023Development of treatment system for periodontal disease and oral cancer using bio-compatible titanium dioxide近年、口腔がんと口腔細菌叢（歯周病菌叢）との関連を示唆する科学的根拠が報告され、注目を集めている(Scientific Reports, 7, 11773 (2017)など)。本研究の目的は、口腔がん、および歯周病の原因となる歯周病菌叢に対して、同一手法で治療する方法を提案する。具体的には、我々が構築した「過酸化チタン粒子」(TiOx)の酸化力、およびその放射線照射法の適用性を適用・検証する事である。本研究の目的は、「過酸化チタン／放射線」照射法を、口腔がんや歯周病菌叢へと適用し、少ない放射線量においてもがん細胞、および細菌損傷に適用可能か検証を行う事である。この研究目的の遂行のために、以下に掲げる2つの項目について検討を行った。 [1] 植物成分でコーティングされた過酸化チタン粒子の開発：TiO2 NPs(石原産業)を元に、RutinG-TiOx NPsと、PAA-TiOx NPsにRutinGを添加したRutinG+PAA-TiOx NPsを作製した。各修飾粒子をUV-visとFT-IRによって、RuitnGのコーティングを確認した。PAA-TiOx NPsと比較したRutinG-TiOxの放射線増感効果の検証するために、H2O2の吸脱着量を化学蛍光法によって定量した。PAA-TiOx及びRutinG-TiOx NPsから219.8, 39.5 micro-mol/gのH2O2が脱着した。この結果より、RutinG-TiOxはPAA-TiOxほどではないがH2O2徐放性を持つことが示唆された。 [2] 過酸化チタン/放射線による治療：in vitroでの放射線増感効果を検証するためコロニーアッセイを行った。5Gyを照射した場合、RutinG-TiOx NPsにもPAA-TiOx NPsと同様に放射線増感効果を持つことが示された。
- 日本学術振興会, 科学研究費助成事業 基盤研究(C), 基盤研究(C), 神戸大学, 01 Apr. 2019 - 31 Mar. 2023血管・リンパ管新生に着眼した歯性感染症－顎骨骨髄炎移行メカニズム解明と治療法探索骨粗鬆症などに対し用いられる骨吸収抑制薬や、口腔癌に対し施行される放射線照射等の医療行為が素因となる顎骨骨髄炎は、近年患者数の増加に伴い顎口腔外科領域において最も新たな治療法開発が期待される難治性疾患の一つである。本研究の目的は、近年感染の進展にも関与していることが明らかとなりつつある血管・リンパ管新生をターゲットとし、歯性感染症－顎骨骨髄炎移行メカニズムを解明することである。 研究の端緒として、まず血管新生のマーカーとなりうる分子の検討を行なった。近年動脈硬化や高血圧、腫瘍の増大における病的な状態における血管新生に関与している可能性が示唆されている血管内皮細胞間接着複合体構成分子に注目した。この分子についてはマウスやヒト培養細胞を用いた研究はこれまでに行われてきたが、ヒトの組織内での発現や局在部位を確認した報告は稀少であった。当該年度の研究結果より、この分子がヒトの組織内でも特に非炎症部位の血管に比べ炎症部位の微小血管等に発現が強く、病的な血管のマーカーとなり得る可能性が示唆された。
- Japan Society for the Promotion of Science, Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (C), Grant-in-Aid for Scientific Research (C), Kobe University, 01 Apr. 2017 - 31 Mar. 2020Skeletal muscle functional magnetic resonance image (muscle functional Magnetic Resonance Image: mfMRI) using a functional image, the change in T2 value before and after exercise for chewing muscle at rest and chewing in healthy subjects (ΔT2) was measured, ΔT2 increase in bilateral masseter during chewing was confirmed. Morphological standardization of masticatory muscles has become possible. Subsequently, when applying mfMRI to oral cancer reconstruction patients, the health side is maintained the same form and muscle mass as before surgery, chewing force was considered to be maintained. On the other hand, since the resection side is excised by surgery, the morphology is changed muscle mass has been reduced, chewing force has been suggested to be reduced.Competitive research funding
- Japan Society for the Promotion of Science, Grants-in-Aid for Scientific Research Grant-in-Aid for Young Scientists (B), Grant-in-Aid for Young Scientists (B), Kobe University, 01 Apr. 2016 - 31 Mar. 2020, Principal investigatorEnhancing the antitumor effect of radiation while reducing organ damage is an important challenge of radiotherapy for oral malignancies. One of the promising radiosensitizers is gold nanoparticles. The aim of this study was to investigate whether gold nanoparticles could enhance the effect of X-ray irradiation on oral cancer cells. In conclusion, the combination of AuNP and x-ray irradiation enhanced the cytotoxic effect on human oral cancer cells in vitro via induction of apoptosis, but did not inhibit cell proliferation.Competitive research funding