Awareness of Complications of Dental Treatment in Patients Treated with Drugs Affecting the Immune System : A Nationwide Questionnaire Survey of Dental Practitioners in Japan.

The aim of this study was to investigate the awareness and experience, among dental practitioners, of adverse events resulting from dental treatment of patients undergoing therapy with drugs that affect the immune system [angiogenesis inhibitors, biological agents, immunosuppressants, and disease-modifying anti-rheumatic drugs (DMARDs)]. For this purpose, a nationwide questionnaire survey was conducted. Questionnaires were sent to 2,050 dentists, of which 206 (10.1%) were completed and returned. The results showed that most dentists were aware of complications associated with dental treatment of patients treated with drugs that affect the immune system, and about half had actually experienced such complications. Delayed wound healing, osteonecrosis of the jaw (ONJ), and postoperative infections were reported. Whereas approximately 50% of dentists did not discontinue the drugs during dental treatment, about 18% did. During temporary drug discontinuation, some patients experienced aggravation of the primary disease, such as worsening of rheumatism, growth of tumors, and rejection reactions of transplanted organs. As for medical cooperation, only less than half of the dentists were asked for oral hygiene management by a physician prior to starting the drug treatment. Prospective studies are needed because evidence for dental treatments in patients treated with these drugs remains limited.

The TRPV4-AKT axis promotes oral squamous cell carcinoma cell proliferation via CaMKII activation.

Most human malignant tumor cells arise from epithelial tissues, which show distinctive characteristics, such as polarization, cell-to-cell contact between neighboring cells, and anchoring to a basement membrane. When tumor cells invaginate into the stroma, the cells are exposed to extracellular environments, including the extracellular matrix (ECM). Increased ECM stiffness has been reported to promote cellular biological activities, such as excessive cellular growth and enhanced migration capability. Therefore, tumorous ECM stiffness is not only an important clinical tumor feature but also plays a pivotal role in tumor cell behavior. Transient receptor potential vanilloid 4 (TRPV4), a Ca2+-permeable nonselective cation channel, has been reported to be mechano-sensitive and to regulate tumorigenesis, but the underlying molecular mechanism in tumorigenesis remains unclear. The function of TRPV4 in oral squamous cell carcinoma (OSCC) is also unknown. The current study was conducted to investigate whether or not TRPV4 might be involved in OSCC tumorigenesis. TRPV4 mRNA levels were elevated in OSCC cell lines compared with normal oral epithelial cells, and its expression was required for TRPV4 agonist-dependent Ca2+ entry. TRPV4-depleted tumor cells exhibited decreased proliferation capabilities in three-dimensional culture but not in a low-attachment plastic dish. A xenograft tumor model demonstrated that TRPV4 expression was involved in cancer cell proliferation in vivo. Furthermore, loss-of-function experiments using siRNA or an inhibitor revealed that the TRPV4 expression was required for CaMKII-mediated AKT activation. Immunohistochemical analyses of tissue specimens obtained from 36 OSCC patients showed that TRPV4 was weakly observed in non-tumor regions but was strongly expressed in tumor lesions at high frequencies where phosphorylated AKT expression was frequently detected. These results suggest that the TRPV4/CaMKII/AKT axis, which might be activated by extracellular environments, promotes OSCC tumor cell growth.

[The clinical effect of combination therapy for oral cancer with S-1, superselective intra-arterial chemotherapy, and radiation therapy].

Combination therapy with S-1, superselective intra-arterial infusion of CBDCA and radiation therapy has been used to treat patients with oral cancer since 2005. In this study, the histopathological effects and toxicities following concurrent chemoradiotherapy were examined. The subjects consisted of 15 patients (10 men and 5 women) who were treated with S-1 (60-80 mg/day, 4 weeks), superselective intra-arterial infusion of CBDCA (300 mg/body) and radiation therapy (total dose 30-36 Gy) in our department from 2005 to 2009. Nine patients, showed T2 disease, 3 showed T3 disease, and another 3 showed T4 diseases. The primary cancer sites were the tongue (6 cases), buccal mucosa (4 cases), mandible gingival (3 cases), maxillary gingiva (1 case), and the floor of the mouth (1 case). The histopathological effects were evaluated according to Oboshi-Shimosato classification. Grade IV was shown in 10 cases (66. 7%), grade III in 1 case (6. 7%), II bin 3 cases (20. 0%), and II a in 1 case (6. 7%). All patients completed the treatment. The pathological response of the resected tumor was grade IIbor higher in 14 cases (93. 3%). While good histological effects were noted, there was one patient for whom viable tumor cells remained in the central part of the tumor. The present study indicates that further investigation is needed to determine the best dosing and dosing schedule.

Questionnaire survey of angiogenesis inhibitor-related oral complications based on a nation-wide study in Japan.

BACKGROUND/PURPOSE: The prevalence of oral adverse events and dental treatments related complications during the molecular targeted drugs therapy remains unclear. The purpose of this study was to investigate the contents of dental treatment-related complications in Japanese patients during molecular targeted therapy. MATERIALS AND METHODS: The nation-wide survey of dental treatment related complications was performed by the Japanese Society of Dentistry for Medically Compromised Patient as retrospective cohort study. RESULTS: Among 212 dentists, 87.3% recognized the possibility of dental treatments related complications in patients with angiogenesis inhibitors. The oral adverse events including dental treatment-related complications associated with angiogenesis inhibitors were 79 cases. In patients with angiogenesis inhibitors, 73.4% of patients were administrated with bevacizumab. The average administration period of angiogenesis inhibitors was 14.0 ±â€¯10.0 months. As the dental treatment related complications, delayed wound healing was most commonly seen in 45 patients (57.0%), followed by osteonecrosis of the jaw in 25 (31.6%). The triggered factor of complications was tooth extraction in 51 cases (96.2%). CONCLUSION: The extraction of the tooth with pre-existing inflammation may be suggested as one of risk factors for angiogenesis inhibitor-related dental treatment complications.

Predictors of early postoperative pneumonia after oncologic surgery with the patients receiving professional oral health care: A prospective, multicentre, cohort study.

This study was a prospective, multicentre, cohort study on 685 patients who had undergone oncologic surgery. The patients were divided into two groups according to the presence or absence of postoperative pneumonia. The two groups were compared with respect to their background, index operation, food eaten, oral condition, contents of oral care and dental treatment, laboratory data, and bacterial flora. All postoperative pneumonias occurred in six cases within four days postoperatively. The multivariable logistic regression analysis showed that preoperative serum C-reactive protein was the strongest predictor of postoperative pneumonia. In addition, decreased postoperative Candida albicans colonies was an effective predictor of postoperative pneumonia. For patients with predictors of postoperative pneumonia, perioperative strategies for its prevention should be considered in addition to professional oral health care. This study was approved by the National Hospital Organization's Central Ethics Review Board and was also approved by the directors of the participating institutions.

[The questionnaire survey to clarify correspondence of medical doctors and dentists in Fukuoka City, Japan, for warfarin therapy at the dental extraction].

PURPOSE: The questionnaire survey was performed in order to clarify correspondence of medical doctors and dentists working at hospital service for warfarin therapy at the dental extraction. METHODS: For 17 senior dentists in 17 hospitals and 142 senior physicians in 82 hospitals in Fukuoka City, we investigated using the questionnaire whether they supported dental extraction under warfarin therapy or not in patients having warfarin treatment with past history of cardioembolic stroke due to non-valvular atrial fibrillation (NVAF). Specialty and experience of stroke after withdrawal of warfarin were also asked in medical doctors. RESULT: The reply was obtained from 14 dentists (82.4%) and 66 doctors (46.5%). The number of dentists and doctors who pull out a tooth under warfarin treatment continuation were 12 persons (85.7%) and 32 persons (48.5%), respectively. The rates in doctors whose specialty was stroke, cardiovascular disease, and others were 78.6% (11/14), 36.0% (9/25), and 44.4% (12/27), respectively. The rate in stroke specialists was significantly higher than that in cardiovascular disease specialists (p = 0.019). The stroke specialists had experience of stroke after withdrawal of warfarin more frequently than the cardiovascular disease specialists (57.1% vs. 20.0%, p = 0.033). CONCLUSION: The rates of acceptance in tooth extraction under warfarin treatment continuation of the dentist were high in Fukuoka city, while that of the medical doctors were not. Rate of doctor's acceptance differed according to the specialties, and may be affected by experience of stroke after cessation of warfarin therapy.

The correlation of histologic features with a panoramic radiography pattern and a computed tomography pattern of bone destruction in carcinoma of the mandibular gingiva.

OBJECTIVE: We sought to clarify the correlation among a computed tomography (CT) or a panoramic radiography (PR) pattern of bone destruction, a histologic pattern of bone destruction, and a mode of invasion in carcinoma of the mandibular gingiva. STUDY DESIGN: CT images, panoramic radiographs, and decalcified, hematoxylin-eosin-stained preparations of the excised mandibular bone of 62 patients with carcinoma of the mandibular gingiva were retrospectively evaluated. Each computed tomograph, panoramic radiograph, and the histologic pattern of bone destruction was classified as 1 of 5 types: erosive, erosive and partly mixed, mixed, mixed and partly invasive, or invasive. The mode of invasion of the tumor was also assessed with a hematoxylin-eosin-stained preparation of the initial biopsy specimen. The relationships among the CT pattern, the PR pattern, the histologic pattern of bone destruction, and the mode of invasion of the tumor were statistically analyzed by using the Spearman rank correlation test. RESULTS: The CT pattern (P =.005) and the PR pattern (P =.003) were significantly correlated with the histologic pattern with respect to the bone destruction. The CT pattern (P =.996), the PR pattern (P =.997), and the histologic pattern (P =.521) of bone destruction were not correlated with the mode of invasion seen in the biopsy specimen. CONCLUSION: The CT pattern and the PR pattern of bone destruction reflect the histologic pattern of bone destruction caused by carcinoma of the mandibular gingiva but are not associated with the mode of invasion of the tumor.

[Questionnaire survey to investigate correspondence of medical doctors and dentists in Japan for antithrombotic therapy at surgeries or biopsy].

PURPOSE: We examined correspondence of doctors and dentists at the time of surgeries or biopsy in patients treated with antithrombotics by questionnaire survey. METHODS: We investigated management of antithrombotic therapy at dental extraction, biopsy or polypectomy under an endoscope, an operation of a cataract, pacemaker implantation by questionnaire survey for doctors and dentists in 64 national hospital organization hospitals (NHO-hospital) and doctors in 163 hospitals participated in the Japan Multicenter Stroke Investigators' Collaboration (J-MUSIC) study. We compared the results between NHO-hospitals and J-MUSIC hospitals. RESULT: The doctor questionary survey got an answer from 103 institutions (63%) out of the 163 J-MUSIC hospitals and 26 institutions (40%) out of 64 NHO-hospitals. The dental extraction under continuation of warfarin therapy in patients with past history of stroke and non-valvular atrial fibrillation or mechanical heart valves was accepted in 35% and 45%, respectively. They were 58% and 69%, respectively in J-MUSIC hospitals and were significantly higher than those in NHO-hospital (p = 0.031 and p = 0.023, respectively). There were no significant differences in antithrombotic management strategies in correspondence to the biopsy, polypectomy or pacemaker implantation between the two groups of hospitals. Continuation of the antithrombotic therapy at surgery to cataracta was more frequent in J-MUSIC hospitals than in NHO-hospitals (nonvalvular atrial fibrillation 48% vs 22% p = 0.015, mechanical heart valve 51% vs 30% p = 0.059). Experience of stroke due to transient withdrawal of warfarin (69% vs 27%, p = 0.0005) and antiplatelet (59% vs 31%, p = 0.022) therapies were more frequently seen in the J-MUSIC hospitals than in the NHO-hospitals. The dentist questionary survey got an answer from 30 institutions (44%) out of the NHO-hospitals. The acceptance rates of dental extraction under continuation of warfarin or antiplatelet therapies were 53% and 60%, respectively. CONCLUSION: It is suggested that constant consensus is provided with a medical institution as for the biopsy, polypectomy, and pacemaker implantation without a difference being seen in both medical institution groups. However, acceptance rate under antithrombotic therapy at dental extraction or surgery for cataracta was higher in the J-MUSIC hospitals than in the NHO-hospitals, which may be due to lack of the consensus to antithrombotic therapy for those surgeries and higher rate of doctors' experience of stroke after withdrawal of antithrombotic therapy in J-MUSIC hospitals.