Antimicrobial susceptibility surveillance of bacterial isolates recovered in Japan from odontogenic infections in 2013.

We report on the findings of the first antimicrobial susceptibility surveillance study in Japan of isolates recovered from odontogenic infections. Of the 38 facilities where patients representing the 4 groups of odontogenic infections were seen, 102 samples were collected from cases of periodontitis (group 1), 6 samples from pericoronitis (group 2), 84 samples from jaw inflammation (group 3) and 54 samples from phlegmon of the jaw bone area (group 4) for a total of 246 samples. The positivity rates of bacterial growth on culture were 85.3%, 100%, 84% and 88.9%, respectively, for groups 1, 2, 3 and 4. Streptococcus spp. isolation rates according to odontogenic infection group were 22% (group 1), 17.7% (group 3) and 20.7% (group 4). Anaerobic isolation rates were 66.9% (group 1), 71.8% (group 3) and 68.2% (group 4). Drug susceptibility tests were performed on 726 strains excluding 121 strains that were undergrown. The breakdown of the strains subjected to testing was 186 Streptococcus spp., 179 anaerobic gram-positive cocci, 246 Prevotella spp., 27 Porphyromonas spp., and 88 Fusobacterium spp. The isolates were tested against 30 antimicrobial agents. Sensitivities to penicillins and cephems were good except for Prevotella spp. The low sensitivities of Prevotella spp is due to ß-lactamase production. Prevotella strains resistant to macrolides, quinolones, and clindamycin were found. No strains resistant to carbapenems or penems were found among all strains tested. No anaerobic bacterial strain was resistant to metronidazole. Antimicrobial susceptibility testing performed on the S. anginosus group and anaerobic bacteria, which are the major pathogens associated with odontogenic infections, showed low MIC90 values to the penicillins which are the first-line antimicrobial agents for odontogenic infections; however, for Prevotella spp., penicillins combined with ß-lactamase inhibitor showed low MIC90 values.

Self-check with plaque disclosing solution improves oral hygiene in schoolchildren living in a children's home.

BACKGROUND: The effectiveness of an oral hygiene program for children living in a children's home has been reported. However, to the best of our knowledge, no studies have evaluated the possible effects of self-checking of oral health among children residing in a children's home. The objective of this study was to examine if self-checking using plaque disclosing solution improves oral hygiene in schoolchildren living in a children's home. METHODS: We enrolled nine schoolchildren (six girls) without untreated decayed teeth living in a children's home in Japan. This preliminary study was designed as a 5-month program comprising group and individual instructions and self-checking using plaque disclosing solution. Paired t-test and Wilcoxon signed-rank test were used for statistical analysis to evaluate the change of Plaque Control Record (PCR) and Patient Hygiene Performance (PHP). RESULTS: The mean PCR significantly decreased to 38.7% after 3 months of self-checking using disclosing solution compared with that before self-checking (i.e., at 1 month) (60.7%) (P < 0.01). PHP score significantly decreased to 1.4 at 4 months compared with that at baseline (2.8) and at 1 month (2.7) (P = 0.012 and P = 0.018). Improvement of oral hygiene status was evaluated according to the ratio of PCR at 4 months to that at 1 month. The average improvement ratio was 0.4 ± 0.35 (range: 0.0-1.0). Significant correlation was not found between improvement rate and school grade (r = 0.63, P = 0.070). CONCLUSIONS: Our results suggest that self-checking with disclosing solution may be effective in improving oral hygiene among schoolchildren at a children's home.

Antiresorptive agent-related osteonecrosis of the jaw: Position Paper 2017 of the Japanese Allied Committee on Osteonecrosis of the Jaw.

Antiresorptive agent-related osteonecrosis of the jaw (ARONJ) is an intractable, though rare, complication in cancer patients with bone metastases and patients with osteoporosis who are treated with antiresorptive agents, including bisphosphonates and denosumab. Despite the more than 10 years that have passed since the first cases of bisphosphonate-related osteonecrosis of the jaw (BRONJ) were reported, our understanding of the epidemiology and pathophysiology of ARONJ remains limited, and data supported by evidence-based medicine are still sparse. However, the diagnosis and staging of ARONJ, identification of risk factors, and development of preventive and therapeutic approaches have advanced significantly over the past decade. The Position Paper 2017 is an updated version of the Position Paper 2010 of the Japanese Allied Committee on Osteonecrosis of the Jaw, which now comprises six Japanese academic societies. The Position Paper 2017 describes a new diagnostic definition for ARONJ, as proposed by the American Association of Oral and Maxillofacial Surgeons (AAOMS), summarizes our current understanding of the pathophysiology of ARONJ based on a literature search, and suggests methods for physicians and dentists/oral surgeons to manage the disease. In addition, the appropriateness of discontinuing antiresorptive medications (drug holiday) before, during, and after invasive dental treatments is discussed extensively. More importantly, the manuscript also proposes, for the first time, the importance of interactive communication and cooperation between physicians and dentists/oral surgeons for the successful treatment of ARONJ. The Position Paper 2017 is intended to serve as a guide for improving the management of ARONJ patients in Japan.

[Corrigendum] Functional analysis of Zyxin in cell migration and invasive potential of oral squamous cell carcinoma cells.

Following the publication of this article, an interested reader drew to our attention an anomaly associated with the presentation of Figs. 2 and 3. Essentially, there was a direct duplication of certain of the western blotting data between Fig. 2 (the E-cadherin and Actin data) and Fig. 3C (the Zyxin and Actin data). After having re-examined our original data, we realize that we inadvertently duplicated the data from Fig. 2 in Fig. 3C (the Zyxin and Actin data). A corrected version of Fig. 3C (containing the true Zyxin and Actin data), and, by natural process, also of Fig. 6, are presented below, in which the Zyxin data in Figs. 3C and 6 are now correctly shown. Since the Zyxin data was a control for the siZyxin knockout of HOC313, this error did not affect the results of the Rho family analysis in this study. We sincerely apologize for this mistake, and thank the reader of our article who drew this matter to our attention. Furthermore, we regret any inconvenience this mistake has caused. [the original article was published in the International Journal of Oncology 42: 873-880, 2013; DOI: 10.3892/ijo.2013.1761].

Establishment of an Animal Model of Bisphosphonate-Related Osteonecrosis of the Jaws in Spontaneously Diabetic Torii Rats.

BACKGROUND: We evaluated the side effects of bisphosphonate (BP) on tooth extraction socket healing in spontaneously diabetic Torii (SDT) rats, an established model of non-obese type 2 diabetes mellitus, to develop an animal model of BP-related osteonecrosis of the jaws (BRONJ). MATERIALS AND METHODS: Male Sprague-Dawley (SD) rats and SDT rats were randomly assigned to the zoledronic acid (ZOL)-treated groups (SD/ZOL or SDT/ZOL) or to the control groups (SD/control or SDT/control). Rats in the SD/ZOL or SDT/ZOL groups received an intravenous bolus injection of ZOL (35 µg/kg) every 2 weeks. Each group consisted of 6 rats each. Twenty-one weeks after ZOL treatment began, the left maxillary molars were extracted. The rats were euthanized at 2, 4, or 8 weeks after tooth extraction, and the total maxillae were harvested for histological and histochemical studies. RESULTS: In the oral cavity, bone exposure persisted at the tooth extraction site in all rats of the SDT/ZOL group until 8 weeks after tooth extraction. In contrast, there was no bone exposure in SD/control or SDT/control groups, and only 1 of 6 rats in the SD/ZOL group showed bone exposure. Histologically, necrotic bone areas with empty lacunae, microbial colonies, and less invasion by inflammatory cells were observed. The number of tartrate-resistant acid phosphatase-positive osteoclasts was lower in the SDT/ZOL group than in the SD/control group. The mineral apposition rate was significantly lower in the SDT/ZOL group compared with the SD/control group. CONCLUSIONS: This study demonstrated the development of BRONJ-like lesions in rats and suggested that low bone turnover with less inflammatory cell infiltration plays an important role in the development of BRONJ.

Dental implant treatment in a young woman after marginal mandibulectomy for treatment of mandibular gingival carcinoma: a case report.

Dental implants play an important role in postoperative rehabilitation after surgical treatment of oral cancer through the provision of prosthetic tooth replacement. Two major implant prosthesis designs are available: fixed implant-supported prostheses and implant-supported overdentures. We herein report a case of a 16-year-old female patient who underwent alveolar ridge resection for treatment of mandibular gingival carcinoma. Following surgery, oral rehabilitation was attempted using an implant-supported overdenture on a gold bar retainer splinting four implants. However, the patient was not satisfied with this prosthesis because of mucosal pain and discomfort, and she gradually ceased its use. Consequently, contact with the opposing teeth caused wear of the prosthetic screws. We elected to replace the implant-supported overdenture with an implant-fixed prosthesis approximately 16 years after insertion of the overdenture to prevent further wear of the prosthetic screws. The patient was highly satisfied with the improved stability of the implant-fixed prosthesis. This case report indicates that the clinician must occasionally re-evaluate and sometimes alter the direction of treatment, even after definitive therapy has been completed.

Is there a first night effect on sleep bruxism? A sleep laboratory study.

STUDY OBJECTIVES: Sleep bruxism (SB) is reported to vary in frequency over time. The aim of this study was to assess the first night effect on SB. METHODS: A retrospective polysomnographic (PSG) analysis was performed of data from a sample of SB patients (12 females, 4 males; age range: 17-39 years) recorded in a sleep laboratory over 2 consecutive nights. Sleep parameters and jaw muscle activity variables (i.e., rhythmic masticatory muscle activity [RMMA]) for SB were quantified and compared between the 2 nights. Subjects were classified into groups according to severity of RMMA frequency, such as low frequency (2-4 episodes/h and/or < 25 bursts/h) and moderate-high frequency (≥ 4 episodes/h and ≥ 25 bursts/h). RESULTS: Overall, no first night effects were found for most sleep variables. However, total sleep time, sleep efficiency, and stage transitions showed significant time and group interactions (repeated measures ANOVAs, p ≤ 0.05). The RMMA episode index did not differ between the 2 nights, whereas the second night showed significantly higher burst index, bruxism time index, and mean burst duration (repeated measure ANOVAs, p ≤ 0.05). Five patients of 8 in the low frequency group were classified into the moderate-high frequency group on the second night, whereas only one patient in the moderate-high frequency group moved to the low frequency group. CONCLUSIONS: The results showed no overall first night effect on severity of RMMA frequency in young and healthy patients with SB. In clinical practice, one-night sleep recording may be sufficient for moderate-high frequency SB patients. However, low RMMA frequency in the first night could be confirmed by a second night based on the patient's medical and dental history.

Effect of a nitric oxide synthase inhibitor and a CXC chemokine receptor-4 antagonist on tumor growth and metastasis in a xenotransplanted mouse model of adenoid cystic carcinoma of the oral floor.

Nitric oxide (NO) is related to angiogenesis and tumor progression and chemokine receptor-4 (CXCR4) plays a central role in cell migration in metastasis and dissemination of cancer. The present study evaluated the effectiveness of a NOS inhibitor and a CXCR4 antagonist, given as single agents or in combination, in a xenotransplanted mouse model of adenoid cystic carcinoma (ACC) of the oral floor. A metastatic tumor (ACCIM) derived from a cervical metastatic lesion of human ACC that was transplantable in nude mice was used. ACCIM showed a high frequency of spontaneous metastasis to the lung when transplanted subcutaneously in nude mice. Mice with subcutaneous transplants of ACCIM were subdivided into six groups and intraperitoneally received one of the following treatments daily for 5 weeks: a) PBS (control), b) AMD3100 (CXCR4 antagonist), c) L-NAME (NOS inhibitor), d) 1400W (iNOS inhibitor), e) both AMD3100 and L-NAME (AMD3100+L-NAME) and f) both AMD3100 and 1400W (AMD3100+1400W). Tumor growth was evaluated during treatment and metastasis was assessed at 28 weeks. Single-agent treatment with AMD3100, L-NAME or 1400W inhibited tumor growth by 20.8, 26.5 and 54.5%, respectively. Combined treatment with AMD3100+L-NAME and AMD3100+1400W inhibited tumor growth remarkably by 48.0 and 50.2%, respectively. Immunohistochemical analysis revealed lower expression of CXCR4, iNOS and eNOS in tumor cells treated with AMD3100+L-NAME or AMD3100+1400W compared to control tumor cells and increased numbers of apoptotic tumor cells were demonstrated using the TUNEL method. CXCR4 expression decreased in 1400W-treated tumors using western blot analysis. When the effect of each agent on tumor-induced angiogenesis in tumor stroma was examined histologically, microvessel density was significantly lower in the groups treated with 1400W, AMD3100+L-NAME or AMD3100+1400W compared to the control, AMD3100 and L-NAME groups. Moreover, treatment with AMD3100 or 1400W markedly inhibited lung metastasis. Our results indicated that single-agent treatment with 1400W and combined treatment with AMD3100+L-NAME or AMD3100+1400W induced apoptosis and significantly inhibited tumor-induced angiogenesis and proliferation of ACCIM in vivo. Blockade of CXCR4 and iNOS was suggested to inhibit lung metastases from ACCIM. CXCR4 and iNOS may, thus, be important prognostic factors for long-term survival in ACC.

Flavor-Enhanced Modulation of Cerebral Blood Flow during Gum Chewing.

BACKGROUND: Flavor perception, the integration of taste and odor, is a critical factor in eating behavior. It remains unclear how such sensory signals influence the human brain systems that execute the eating behavior. METHODS: WE TESTED CEREBRAL BLOOD FLOW (CBF) IN THE FRONTAL LOBES BILATERALLY WHILE SUBJECTS CHEWED THREE TYPES OF GUM WITH DIFFERENT COMBINATIONS OF TASTE AND ODOR: no taste/no odor gum (C-gum), sweet taste/no odor gum (T-gum), and sweet taste/lemon odor gum (TO-gum). Simultaneous recordings of transcranial Doppler ultrasound (TCD) and near infrared spectrometer (NIRS) were used to measure CBF during gum chewing in 25 healthy volunteers. Bilateral masseter muscle activity was also monitored. RESULTS: We found that subjects could discriminate the type of gum without prior information. Subjects rated the TO-gum as the most flavorful gum and the C-gum as the least flavorful. Analysis of masseter muscle activity indicated that masticatory motor output during gum chewing was not affected by taste and odor. The TCD/NIRS measurements revealed significantly higher hemodynamic signals when subjects chewed the TO-gum compared to when they chewed the C-gum and T-gum. CONCLUSIONS: These data suggest that taste and odor can influence brain activation during chewing in sensory, cognitive, and motivational processes rather than in motor control.

Comparison of joint pain in patients diagnosed with and without articular disc displacement without reduction based on the Research Diagnostic Criteria for Temporomandibular Disorders.

OBJECTIVE: We compared joint pain (JP) in patients diagnosed with and without articular disc displacement without reduction (ADD) based on the Research Diagnostic Criteria for Temporomandibular Disorders (RDC/TMD) and identified the characteristics of each JP. STUDY DESIGN: Fifty-eight patients with restricted mouth opening and pain in temporomandibular joint (TMJ) and with a magnetic resonance imaging diagnosis of ADD were selected. Diagnosis of ADD + JP and nonADD + JP was made with the use of the RDC/TMD. RESULTS: A multiple regression analysis of the data disclosed a positive correlation between range of motion on maximum assisted mouth opening and visual analog scale (VAS) (severity of JP) in the ADD + JP group, and between chronic pain grade (CPG) and VAS in the nonADD + JP group. A significant difference was observed between ADD + JP and nonADD + JP groups in CPG; CPG was higher in the nonADD + JP than in the ADD + JP group. CONCLUSIONS: It is suggested that JP related and unrelated to ADD can indicate different types of disease.

Functional analysis of Zyxin in cell migration and invasive potential of oral squamous cell carcinoma cells.

Zyxin is an evolutionarily conserved protein that has been implicated in the regulation of actin assembly and is mainly located at focal adhesions. However, the biological roles of Zyxin in cancer cells are incompletely understood. We analyzed the functions of Zyxin in cell migration and the invasive potential of OSCC. Zyxin expression was examined using eight OSCC cell lines with two different cell morphologies (6 epithelial type and 2 fibroblastic type). To knockdown Zyxin expression, OSCC cells were transfected with Zyxin siRNA and control siRNA. The cell lines were studied by western blot analysis, immunocytochemical analysis and cell migration and invasion assay. Epithelial type OSCC cells showed a high level of E-cadherin expression and a low level of Zyxin expression. N-cadherin as well as Zyxin were strongly expressed in fibroblastic type OSCC cells. Expression levels of LPP and TRIP6, members of the human Zyxin family, did not differ between epithelial type and fibroblastic type. Knockdown of Zyxin expression by siRNA in fibroblastic type OSCC cells was associated with cell morphological changes from spindle (fibroblastic) to polygonal (epithelial) shape and significantly inhibited cell growth as well as cell migration and invasion. Expression levels of Rac1 and Cdc42 were weaker in Zyxin siRNA-treated fibroblastic type OSCC cells than in control siRNA-treated cells, but the expression of RhoA did not differ significantly. Treatment of fibroblastic type OSCC cells with Rac1 inhibitor decreased the expression of Zyxin mRNA and protein. Zyxin is suggested to promote growth, migration and invasiveness of fibroblastic type OSCC cells by upregulating Rac1 and Cdc42.

Unicystic ameloblastoma metastasizing to multiple cervical lymph nodes.

Ameloblastoma is the most common odontogenic tumor, but the incidence of its metastasis is extremely low. We report a case of unicystic ameloblastoma metastasizing to the cervical lymph nodes. This patient pointed out a radiolucent cystic lesion with impacted wisdom tooth in the left mandibular region, and recieved enucleation of the cystic lesion and removal of the wisdom tooth. Histopathogical diagnosis was unicystic ameloblastoma. Three years later, this patient complained of a swelling in the left submandibular region. A CT scan showed a bilobed cystic mass measuring 30 mm in diameter compressing the submandibular gland, and we performed extirpation of the mass with the submandibular gland and associated lymph nodes. Histologically, the lesion was cystic and lymph follicles were seen in the cyst-like wall. The laminated epithelium of cyst wall was ameloblastomatous epithelium, and two lymph nodes associated with cystic lesion also included ameloblastomatous epithelium. This is the first report of metastasizing unicystic ameloblastoma.

Influence of dentures in the initial occurrence site on the prognosis of bisphosphonate-related osteonecrosis of the jaws: a retrospective study.

OBJECTIVE: This retrospective cohort study was conducted to investigate the influence of wearing dentures in the initial occurrence site of bisphosphonate-related osteonecrosis of the jaws (BRONJ). STUDY DESIGN: A questionnaire regarding the prevalence, therapy, and outcome of jawbone lesions during 2006-08 was mailed to 248 medical institutions with an oral and maxillofacial surgery department in Japan. RESULTS: Ninety-nine patients wearing dentures had significantly shorter duration until occurrence than 151 patients not wearing dentures. In addition, remission of BRONJ affecting the mandibular canine and premolar region in denture-wearing patients was significantly more difficult. Poor oral hygiene status was found to affect significantly the prognosis of BRONJ in denture-wearing patients. Alcohol habit also delayed remission, but high body mass index promoted remission. CONCLUSION: Wearing a denture in the initial occurrence site of BRONJ was shown to influence the prognosis of BRONJ, especially in mandibular denture-wearing patients.

Diffuse sclerosing osteomyelitis of the mandible successfully treated with pamidronate: a long-term follow-up report.

Diffuse sclerosing osteomyelitis of the mandible (DSOM) is an uncommon chronic inflammatory disease of bone that is refractory to conventional treatments, such as antibiotics, nonsteroidal anti-inflammatory drugs, and decortication. We report a case of chronic DSOM of 15 years' duration in a 61-year-old woman that was successfully treated with a single infusion of pamidronate. Persistent, intractable pain resolved 3 days after infusion. Intense accumulation on (99m)Tc scintigraphy decreased 2 months after infusion, and almost disappeared after 3 years. Panoramic radiography demonstrated a clear decrease in pathologic changes, close to that of normal bone architecture, which has not been reported in DSOM treated with bisphosphonates.

Cisplatin-induced acute renal failure in mice is mediated by chymase-activated angiotensin-aldosterone system and interleukin-18.

Mechanism(s) of cisplatin-induced acute renal failure, as manifested by increases in blood urea nitrogen and creatinine, was evaluated in relation to production and activation of endogenous mediator(s) in mice. In interleukin (IL)-18-deficient (IL-18KO) mice, cisplatin failed to induce acute renal failure. Administration of recombinant IL-18 prior to cisplatin restored acute renal failure in IL-18KO mice. Accumulation of cisplatin in the kidney was not different in IL-18KO and wild-type (WT) mice, but, clearance of cisplatin was more rapid in IL-18KO mice than in WT mice. Cisplatin increased serum levels of aldosterone and angiotensin II in WT mice, but only angiotensin II levels in IL-18 KO mice. Administration of IL-18 augmented plasma levels of aldosterone and angiotensin II in WT mice. Eplerenone, an aldosterone receptor blocker, TY-51469, a chymase inhibitor and PD123319, a selective angiotensin II type 2 (AT2) receptor antagonist, but not benazepril, an angiotensin-converting enzyme inhibitor, and candesartan, a selective angiotensin II type 1 (AT1) receptor antagonist improved acute renal failure caused by cisplatin, confirming involvement of IL-18, aldosterone and angiotensin II in cisplatin-induced, chymase-dependent acute renal failure in mice. These results show that IL-18, aldosterone and angiotensin II synergistically act to prolong the accumulation of cisplatin in the kidney, leading to acute renal failure. Combined therapy with inhibitors for chymase and aldosterone receptors or AT2 receptors might reduce acute renal failure induced by cisplatin.

The promotional effect of IL-22 on mineralization activity of periodontal ligament cells.

OBJECTIVES: Interleukin (IL)-22 acts on non-immune cells to induce anti-microbial responses, protection from tissue damage, and enhance cell regeneration. However, little is known about the involvement of IL-22 in periodontal biology. This study investigated the biological effects of IL-22 on periodontal ligament (PDL) cells as part of studies to assess the involvement of IL-22 in periodontal disease. MATERIALS AND METHODS: Gene expression levels of IL-22 and its receptors in PDL cells and gingival tissue samples were evaluated by real-time PCR. Proliferative responses and mineralized-matrix forming activities of PDL cells were examined in the presence and absence of IL-22. RESULTS: In contrast to the expression of IL-22 receptors detected in PDL tissues and their cell lines, gingival tissues showed modest or no gene expressions of IL-22. The production of several cytokines including IL-11, IL-8 and CCL2 was upregulated by IL-22 treatment of PDL cells in a dose-dependent manner. IL-22 treatment had no effect on the proliferative response in PDL cells. Meanwhile, IL-22 precipitated mineralized nodule formation and induced gene expressions of RUNX2, MSX2 and osteocalcin in PDL cells, suggesting that IL-22 enhances the mineralized matrix-forming activities of PDL cells. CONCLUSION: IL-22 has the potential to promote mineralizing activity in PDL cells and to develop appropriate regenerative therapy.

An in vitro multistep carcinogenesis model for both HPV-positive and -negative human oral squamous cell carcinomas.

Oral squamous cell carcinomas (OSCCs) are considered to arise from human oral keratinocytes. DNAs of human papillomaviruses (HPVs), predominantly types 16 and 18, etiological agents of cervical cancer, have been detected in approximately 25% of OSCCs. In accordance with the established role of E6 and E7 in inactivating p53 and pRB, respectively, mutations of p53 and inactivation of p16(INK4a) are frequently observed in HPV-negative OSCCs. In addition, other alterations such as overexpression of epidermal growth factor receptor (EGFR) are often observed in both HPV-positive and -negative OSCCs. However, causal-relationships between accumulation of these abnormalities and multi-step carcinogenesis are not fully understood. To elucidate underlying processes, we transduced either HPV16 E6/E7 or mutant CDK4 (CDK4(R24C)), cyclin D1 and human telomerase reverse transcriptase (TERT) into primary human tongue keratinocytes (HTK), and obtained immortal cell populations, HTK-16E6E7 and HTK-K4DT. Additional transduction of oncogenic HRAS or EGFR together with MYC into the HTK-16E6E7 and dominant-negative p53 expressing HTK-K4DT resulted in anchorage-independent growth and subcutaneous tumor formation in nude mice. These results indicate that either HRAS mutation or activation of EGFR in cooperation with MYC overexpression play critical roles in transformation of HTKs on a background of inactivation of the pRB and p53 pathways and telomerase activation. This in vitro model system recapitulating the development of OSCCs should facilitate further studies of mechanisms of carcinogenesis in the oral cavity.

Up-regulation of neutrophil gelatinase-associated lipocalin in oral squamous cell carcinoma: relation to cell differentiation.

Neutrophil gelatinase-associated lipocalin (NGAL, also known as lipocalin2, LCN2) is a secreted glycoprotein with increased expression in solid tumors. The expression and functions of NGAL in oral cancer, however, remain unclear. We investigated the expression of NGAL in oral cancer tissues and oral cancer cell lines. By immunohistochemical examinations, NGAL expression was strongly up-regulated in well-differentiated OSCC tissues and moderately to weakly up-regulated in moderately to poorly differentiated OSCC tissues. In contrast, NGAL expression was weak or very weak in normal mucosa and leukoplakia. By western blot analysis, NGAL expression levels positively correlated with cell morphology patterns and loss of E-cadherin. In addition, the enzymatic activity of the NGAL/MMP-9 complex significantly correlated with the results obtained by zymographic analysis. In conclusion, NGAL expression is high in well-differentiated cancer, suggesting that NGAL may be a useful diagnostic marker of tumor-cell differentiation.

Nationwide survey for bisphosphonate-related osteonecrosis of the jaws in Japan.

PURPOSE: A nationwide retrospective cohort study was conducted by the Japanese Society of Oral and Maxillofacial Surgeons to assess the occurrence of bisphosphonate (BP)-related osteonecrosis of the jaws (BRONJ) during 2006 to 2008 and to elucidate the outcome and factors associated with remission of BRONJ. MATERIALS AND METHODS: A written questionnaire, including the clinical characteristics, management, and outcome of patients with BRONJ, was sent to 248 institutions certified as training facilities by the Japanese Society of Oral and Maxillofacial Surgeons in 2008. RESULTS: A total of 568 patients with BRONJ, including suspicious cases, were registered. Of these 568 patients, 263, including the maxilla in 81, the mandible in 160, and both in 22, met the working definition of BRONJ proposed by the American Association of Oral and Maxillofacial Surgeons. The patients included 219 women (83.3%) and 44 men (16.7%). Of these patients, 152 (57.8%) had received intravenous BPs, 104 (39.5%) had received oral BPs, and 7 (2.7%) had received both. The mean duration of administration until onset of BRONJ was 23.6 months for intravenous BPs and 33.2 months for oral BPs. BRONJ was stage 1 in 42 patients (16.0%), stage 2 in 187 (71.1%), stage 3 in 32 (12.2%), and unknown in 2. Of these patients, 34.2% had remission of BRONJ, 46.0% had persistent or progressive disease, and 19.7% died of malignancy or were lost to follow-up. Statistical analysis revealed that surgical treatment, including tooth extraction, sequestrectomy, and segmental mandibulectomy, contributed to the remission of BRONJ. In contrast, conservative treatment, concurrent anticancer drugs, poor oral hygiene, and the use of intravenous BPs did not. CONCLUSIONS: The relative ratio of BRONJ related to the use of oral BPs was greater in Japan than in the United States and European Union. Surgical treatment contributed to remission of BRONJ, and conservative treatment, concurrent anticancer drugs, poor oral hygiene, and intravenous BPs did not.