Potential involvement of chondroitin sulfate A in the pathogenesis of ameloblastoma.

Ameloblastoma is classified as a benign odontogenic tumor characterized by locally invasive behavior and high risk of recurrence. Here, we evaluate a potential role for glycosaminoglycan, a structural component of cell membranes and extracellular matrix, in ameloblstoma pathogenesis. We subjected formalin-fixed, paraffin-embedded tissue sections of 34 cases of ameloblastoma, 10 of odontogenic keratocyst, and 17 of dentigerous cyst to immunohistochemistry using monoclonal antibodies recognizing chondroitin sulfate A (CS-A), heparan sulfate (HS), and keratan sulfate (KS). Expression levels of CS-A in epithelial component and stroma of ameloblastoma were significantly higher than those in odontogenic keratocyst and dentigerous cyst. Moreover, CS-A in ameloblastoma was more strongly expressed in stellate reticulum-like cells than in amelobast-like cells with statistical significance. On the other hand, expression levels of HS and KS in epithelial component and stroma of ameloblastoma were lower compared with CS-A. These results overall reveal that among these odontogenic lesions, CS-A is preferentially expessed in ameloblastoma, suggesting potential pathogenetic role probably in cytodifferention of tumor cells to stellate reticulum-like cells.

Candida concentrations determined following concentrated oral rinse culture reflect clinical oral signs.

BACKGROUND: Oral candidiasis is an infection caused by a yeast-like fungus called Candida. Various methods can be used to isolate Candida from the oral cavity. However, it is difficult to correctly and satisfactorily diagnose oral candidiasis because currently no microbiological or laboratory standards based on samples from the oral cavity are available. The aim of this study is to establish a reliable laboratory test for diagnosing oral candidiasis. METHODS: Oral swab, rinse and concentrated rinse samples were obtained from 200 consecutive outpatients (103 male patients and 97 female patients; mean age, 47.2 years; age range, 9-89 years). Candida colonies from cultured samples were enumerated to compare the sensitivities and specificities of the above sampling methods, and the associations between Candida detection or concentration and the clinical oral signs were examined. RESULTS: The mean colony numbers were 263 ± 590 CFU/swab for the swab method, 2894 ± 6705 CFU/100 µL for the rinse method, and 9245 ± 19,030 CFU/100 µL for the concentrated rinse method. The median numbers were 23 CFU/swab for the swab method, 56 CFU/100 µL for the rinse method, and 485 CFU/100 µL for the concentrated rinse method. Candida was detected in the oral cavity of 33.5 % and 52.0 % of the outpatients by the swab method and concentrated rinse, respectively. Candida concentrations determined by the concentrated rinse were closely related to the severity of the clinical oral signs. The positive predictive values of residual root, redness of the oral mucosa, denture, glossalgia, dry mouth, and taste disorder were useful predictors of oral candidiasis. CONCLUSIONS: Concentrated rinse sampling is suitable for evaluating oral candidiasis, and Candida concentrations examined using this method strongly associated with the oral signs associated with Candida infection.

Evaluation of postextraction bleeding incidence to compare patients receiving and not receiving warfarin therapy: a cross-sectional, multicentre, observational study.

OBJECTIVES: We investigated incidence and risk factors for postextraction bleeding in patients receiving warfarin and those not receiving anticoagulation therapy. DESIGN: Cross-sectional, multicentre, observational study. SETTING: 26 hospitals where an oral surgeon is available. PARTICIPANTS: Data on 2817 teeth (from 496 patients receiving warfarin, 2321 patients not receiving warfarin; mean age (SD): 62.2 (17.6)) extracted between 1 November 2008 and 31 March 2010, were collected. Warfarin-receiving patients were eligible when prothrombin time-international normalised ratio (PT-INR) measured within 7 days prior to the extraction was less than 3.0. INTERVENTIONS: Simple dental extraction was performed, and incidence of postextraction bleeding and comorbidities were recorded. PRIMARY AND SECONDARY OUTCOME MEASURES: Postextraction bleeding not controlled by basic haemostasis procedure was clinically significant. RESULTS: Bleeding events were reported for 35 (7.1%) and 49 (2.1%) teeth, of which 18 (3.6%) and 9 (0.4%) teeth were considered clinically significant, in warfarin and non-warfarin groups, respectively, the difference between which was 3.24% (CI 1.58% to 4.90%). The incidence rates by patients were 2.77% and 0.39%, in warfarin and non-warfarin groups, respectively (incidence difference 2.38%, CI 0.65% to 4/10%). Univariate analyses showed that age (OR 0.197, p=0.001), PT-INR (OR 3.635, p=0.003), mandibular foramen conduction anaesthesia (OR 4.854, p=0.050) and formation of abnormal granulation tissue in extraction socket (OR 2.900, p=0.031) significantly correlate with bleeding incidence. Multivariate analysis revealed that age (OR 0.126, p=0.001), antiplatelet drugs (OR 0.100, p=0.049), PT-INR (OR 7.797, p=0.001) and history of acute inflammation at extraction site (OR 3.722, p=0.037) were significant risk factors for postextraction bleeding. CONCLUSIONS: Our results suggest that there is slight but significant increase in the incidences of postextraction bleeding in patients receiving warfarin. Although absolute incidence was low in both groups, the bleeding risk is not negligible.

Temporomandibular joint response to mandibular deviation in rabbits detected by 3D micro-CT imaging.

PURPOSE: Micro-computed tomography enables continuous and dynamic observation of the three-dimensional morphology of small structures. We observed morphological changes of the temporomandibular joint condyle under mandibular deviation continuously in an animal model by micro-computed tomography. METHODS: Twelve Dutch rabbits were used (9 as experimental and 3 as control). In the experimental rabbits, the mandible was deviated posteriorly on the left side using an elastic band. Bilateral temporomandibular joints were scanned by micro-computed tomography preoperatively and at 3, 6, and 12 weeks after the operation. Histopathological examination was also carried out to confirm the changes. RESULTS: It was shown that mandibular deviation induces condyle resorption in either ipsilateral or contralateral temporomandibular joint, which consequently makes the condyle smaller. Bone resorption settled down earlier in the contralateral joint and the quantity of bone resorption on the contralateral side was smaller than on the experimental side. Histopathological examination also showed destructive bone changes in the condyle, although they could not completely reflect the morphological changes. CONCLUSIONS: These results suggested that reduction of the condylar size occurred as an adaptive change to mandibular deviation.

Multicenter phase 2 study of induction chemotherapy with docetaxel and nedaplatin for oral squamous cell carcinoma.

PURPOSE: To determine the clinical and hisotological efficacy and toxicities of induction chemotherapy with docetaxel (DOC) and nedaplatin (CDGP) for oral squamous cell carcinoma (OSCC) in the preoperative setting. METHODS: A total of 30 patients with locally advanced but operable OSCC were enrolled. Combination induction chemotherapy consisted of DOC 60 mg/m2 followed by CDGP 100 mg/m2. RESULTS: All patients received one cycle of chemotherapy. In the clinical assessment, ten patients achieved partial response for an overall response rate of 33.3% (95% CI, 16.4-50.2%). Histological assessment of surgical specimens showed an overall response rate of 56.6% (95% CI, 38.9-74.3%). Although severe neutropenia was observed in 90% of patients, only one patient (3.3%) experienced severe infection. Toxicities associated with this regimen did not interfere with planned radical surgery. CONCLUSIONS: A single cycle of preoperative combination chemotherapy with DOC and CDGP showed moderate histological activity with an acceptable safety profile for the planned radical surgery. Further studies testing more cycles before surgery might be more appropriate.

Usefulness of a commercial enzyme-linked immunosorbent assay kit for Candida mannan antigen for detecting Candida in oral rinse solutions.

OBJECTIVE: The aim was to test the performance of a commercial enzyme-linked immunosorbent assay (ELISA) kit for Candida mannan antigen for detecting Candida in oral rinse solutions. STUDY DESIGN: Forty-eight oral rinse solutions (38 from patients and 10 from healthy volunteers) were available. Mannan antigen was measured using a commercial sandwich ELISA kit, Unimedi Candida. The result of the mannan assay was compared with the result of conventional detection and identification by culture. RESULTS: The result of the mannan assay revealed that 31 of 38 clinical and 3 of 10 healthy volunteer samples were positive for Candida. Using the culture as a gold standard, the overall sensitivity and specificity of the mannan antigen detection were 90.9% and 46.2%, respectively. CONCLUSIONS: The results of this study suggested that mannan antigen detection might be a possible and sensitive technique for the detection of oral Candida. The conditions of the ELISA-based assay should be optimized for oral rinse solutions.

Intraoperative tissue staining of invaded oral carcinoma.

The purpose of this study was to assess the ability of intraoperative tissue staining with consecutive application of 0.4% indigo carmine and 0.5% Congo red to demonstrate the extent and border of oral carcinoma invasion. Seventeen patients were included in the study. Once the oral tumor was resected, a vertical section of surgical specimen was taken from the central part of the tumor. The extent and border of the invaded carcinoma were assessed on digital microscopic examination with tissue staining. The results of assessments were compared with corresponding results of conventional histopathological analysis with HE staining, which is considered the gold standard. Tissue staining produced a brown-black stain on normal muscle, connective, and salivary tissues but not tumor and epithelial tissues. It clearly demonstrated the extent and border of tumor invasion in 13 of 17 patients (76.5%); however, detection of remnant vital tumor cells in scar tissue after neoadjuvant chemotherapy, and distinction between the tumor and adipose tissue scattered in the muscle tissue was difficult. The results of this study showed that intraoperative tissue staining was a possible method in demonstrating the extent and border of carcinoma deeply invaded in the soft tissue and selecting the site for additional frozen section analysis, although the method needed some refinement.

Dental rehabilitation using an implant-carrying plate system in a severely resorbed edentulous maxilla: a case report.

This clinical article describes a case of dental rehabilitation using an implant-carrying plate system (EPITEC) for a patient with severely resorbed edentulous maxilla and microstomia. In this case, the presence of microstomia prevented bone augmentation procedures through an intraoral approach. Treatment using 2 endosseous implants inserted in the canine regions and an implant-supported overdenture was planned. However, endosseous implants were not feasible on the right side because of insufficient available bone volume. An implant-carrying plate system was then utilized on the right side. Four months later, an implant-supported ball-attachment overdenture was fabricated. At the 2-year follow-up, the clinical course remained uneventful, and the patient remained satisfied with the treatment.

Accuracy of intraoperative tissue staining in delineating deep surgical margins in oral carcinoma surgery.

The purpose of this study was to assess the accuracy of this tissue staining assessment of surgical specimens in delineating deep surgical margins in oral cancer surgery. Fifteen patients who underwent surgery for oral carcinoma were included in the study. Once the tumor was resected, a vertical section of the surgical specimen was taken from the central part of the tumor. The section was consecutively stained with 0.4% indigo carmine and 0.5% Congo red, and deep surgical margins were assessed using a digital microscope with a magnification power of 25-175x. The results of tissue staining analysis were compared with the corresponding results of conventional histopathological analysis with HE staining, which is considered the gold standard. The extent of carcinoma invasion could be visualized after the application of tissue staining solutions. Tissue staining analysis was accurate in 12 of the 15 patients (80%) in evaluating the closest deep surgical margin. There was no significant difference in the tumor-margin distance between tissue staining and histopathological assessment in these 12 patients (Wilcoxon signed-ranks test, P>0.63). The results of this study showed that intraoperative tissue staining of surgical specimens permitted visual inspection and assessment of tumor spread to surgical margin, although the method has some limitations. The method had a possible ability in controlling the deep surgical margin.

Comparison of imaging follow-up between joints with arthroscopic surgery (lysis and lavage) and those with nonsurgical treatment.

PURPOSE: To assess the influence of arthroscopic surgery on radiographically evident degenerative change of the temporomandibular joint (TMJ). The post-treatment course was compared between the joints that underwent arthroscopic lysis and lavage and those that underwent nonsurgical treatment. PATIENTS AND METHODS: Twenty-eight patients agreed to imaging follow-up examination of 35 joints. Twenty-four joints of 19 patients underwent only nonsurgical treatment (nonsurgical joints). Eleven joints of 9 patients failed the nonsurgical treatment and consequently underwent arthroscopic lysis and lavage (arthroscopic joints). The joints were assessed at first visit and at least 20 months later (mean, 79 months) for disc displacement, disc position, disc morphology, disc mobility, condylar morphology, morphology of the articular eminence, and horizontal condylar angle and size. Thereafter, interval change was assessed and compared between the groups. RESULTS: There was no significant difference in the prevalence of the progressive degenerative changes between the groups. In addition, there was no significant difference in the change of size and morphology of the condyle. However, a higher prevalence of improvement of disc mobility in the arthroscopic joints rather than the nonsurgical joints was significant (Goodness of fit test for chi(2), P < .05). CONCLUSIONS: The results of this study suggest that the post-treatment course of radiographically evident degenerative change was not significantly different between arthroscopy and nonsurgical treatment; however, arthroscopic surgery showed a greater ability to improve disc mobility. In imaging follow-up, arthroscopic lysis and lavage is a minimally invasive treatment modality that is equivalent to nonsurgical treatment.

Immunohistochemical study of hard tissue formation in the rat pulp cavity after tooth replantation.

While mineralized tissue is formed in the pulp cavity after tooth replantation or transplantation, little is known of this hard tissue formation. Therefore, we conducted histological and immunohistochemical evaluations of hard tissue formed in the pulp of rat maxillary molars after tooth replantation. At 5 days after replantation, degenerated odontoblasts were lining the pulp cavity. At 14 days, dentin- or bone-like tissue was present in the pulp cavity. Immunoreactivity for osteopontin (OPN) and bone sialoprotein (BSP) was strong in the bone-like tissue, but weak in the dentin-like tissue. Conversely, dentin sialoprotein (DSP) was localized in the dentin-like tissue, but not in the bone-like tissue. Cells positive for BMP4, Smad4, Runx2, and Osterix were found around the blood vessels of the root apex at 5 days. At 14 days, these cells were also localized around the bone-like tissue. Cells expressing alpha-smooth muscle actin (SMA) were seen around the newly formed bone-like tissue, whereas no such cells were found around the newly formed dentin-like tissue. In an experiment involving the transplantation of a green fluorescent protein (GFP)-transgenic rat tooth into a wild-type rat tooth socket, GFP-positive cells were detected on the surface of the bone-like tissue and over all dentin-like tissue. These results indicate that the original pulp cells had the ability to differentiate into osteoblast-like cells as well as into odontoblast-like cells.

Retrospective analysis on prognostic impact of adjuvant chemotherapy in the patients with advanced and resectable oral squamous cell carcinoma.

PURPOSE: The effect of adjuvant chemotherapy on oral squamous cell carcinoma (SCC) is unclear mainly because there have been a few studies which evaluate the efficacy of adjuvant chemotherapy. The purpose of this retrospective study was to analyze the efficacy of adjuvant chemotherapy in the patients with advanced and resectable oral SCC. METHODS: 41 patients in whom advanced SCC (stage III and IV) was completely removed were included in this study. The impact of multiple variables including T-classification, degree of differentiation, mode of invasion, number and level of cervical metastatic node, pre-and post-operative radiation therapy, neoadjuvant chemotherapy, and adjuvant chemotherapy on survival and control of local relapse or distant metastasis was assessed using the stepwise Cox proportional hazards model. RESULTS: The level of neck node metastasis (p<0.02) was a significant independent predictor for cause-specific survival and adjuvant chemotherapy was of borderline significance (p=0.07). The number of neck node metastasis (p<0.01) and adjuvant chemotherapy (p<0.01) were significantly related with disease free survival. CONCLUSION: The results of this retrospective study suggested that adjuvant chemotherapy had a significant benefit in improving disease free survival.

Intraoperative digital microscopic assessment of the deep surgical margins in oral carcinoma surgery: a preliminary report.

BACKGROUND: This study assessed the possible ability of intraoperative digital microscopic analysis to control the deep surgical margin in oral carcinoma surgery. METHODS: A vertical section of a surgical specimen was taken from the central part of the resected tumor. The section was assessed using a digital microscope. The results of digital microscopic analysis were compared with the corresponding results of the conventional histopathologic assessment. RESULTS: The method was accurate in 10 of the 12 patients (83%) in evaluating the closest deep surgical margin. There was no significant difference in the tumor-margin distance between the digital microscopic and the histopathologic assessments in these 10 patients (Wilcoxon signed-rank test, P > .13). CONCLUSIONS: The digital microscopic examination was useful in controlling deep surgical margins and selecting the nearest margin for additional frozen section analysis. Additional methods that could clarify the difference between the tumor and fibrous tissue are necessary.

Radiographic follow-up of diseased temporomandibular joints.

OBJECTIVE: The objective of this study was to assess the long-term course of radiographically evident degenerative changes of the soft and hard tissues of the temporomandibular joint (TMJ) in patients with TMJ disorders. STUDY DESIGN: Twenty-one patients (33 joints) were included in the study. The results of radiographic assessments at the first visit and at least 46 months after the first visit (mean 96.0 months) were compared. RESULTS: All subjects had a good clinical course after a favorable response to treatment. Radiographic assessment showed that there was a statistically significant change in disk morphology during the intervening years, with the disks becoming more deformed (P < .05, McNemar test). On the other hand, there was no significant change in the condylar morphology or size. CONCLUSIONS: Most of the acute and destructive radiographically visible degenerative changes were arrested or slowed in the patients whose symptoms and signs were successfully resolved or reduced, while disk deformation significantly progressed.

Dihydropyrimidine dehydrogenase expression predicts survival outcome and chemosensitivity to 5-fluorouracil in patients with oral squamous cell carcinoma.

Dihydropyrimidine dehydrogenase (DPD) is the rate-limiting enzyme of 5-fluorouracil (5-Fu) catabolism. The aim of this study was to evaluate the prognostic value of DPD expression and the correlation between DPD expression and efficacy of 5-Fu. Retrospective analysis of DPD expression was performed immunohistochemically in 103 patients with oral squamous cell carcinoma (OSCC), in which staining intensity of DPD expression and degree of heterogeneity of DPD expression were categorized. Expression of DPD correlated with lymph node metastasis, mode of invasion and differentiation. Expression of DPD was an independent significant factor for survival outcome and was more predictive than conventional clinical factors. Furthermore, heterogeneous expression of DPD was more effective than homogeneous expression of DPD in neoplastic cells when evaluated in patients treated with chemotherapy including tegafur/uracil (UFT). Expression of DPD is an independent predictor for clinical outcome. Furthermore, heterogeneity of DPD expression may be a clue for predicting sensitivity to 5-Fu in patients with OSCC.

Multicenter phase I trial of induction chemotherapy with docetaxel and nedaplatin for oral squamous cell carcinoma.

A phase I study of combination neoadjuvant chemotherapy with docetaxel (DOC) and nadaplatin (CDGP) was conducted in patients with untreated, advanced but operable oral squamous cell carcinoma. DOC was administered (one-hour i.v. infusion) on day 1 followed by CDGP (one-hour i.v. infusion). The dose levels of DOC and CDGP tested were 60/70, 60/80, 60/90, 60/100, and 70/100 (mg/m(2)). Fifteen patients enrolled in this study and median age was 60 years. Dose-limiting toxicity (DLT) occurred in one of six patients at DOC dose of 60 mg/m(2) and CDGP dose of 100 mg/m(2). The DLT was diarrhea. Because one additional patient at this dose-level developed grade 4 neutropenia lasting for 4 days that approached DLT and because fear of severe hematological problems was predicted, further dose escalation was not performed. This combination chemotherapy is active and well tolerated and warrants a phase II study. We recommended 60 mg/m(2) DOC and 100 mg/m(2) CDGP for phase II study.

Clinical predictors for contralateral neck lymph node metastasis from unilateral squamous cell carcinoma in the oral cavity.

The factors that predict contralateral (C-) lymph node metastasis (LNM) in patients with unilateral oral squamous cell carcinoma (SCC) were analyzed. One hundred and twenty-nine patients who had untreated SCC that originated from the lateral oral cavity, but not around the midline, were included. The impact of multiple clinicopathologic factors (sex, performance status, primary site, T-stage, number and level of ipsilateral LNM, growth type, histopathological grading, mode of invasion, extension across the midline, and systemic neoadjuvant/adjuvant chemotherapy) on time-to-C-LNM was assessed using the stepwise Cox proportional hazards model. The T-stage, number of ipsilateral LNM, and histopathological grading were independent and significant predictors for C-LNM. No C-LNM occurred in patients without ipsilateral LNM and in those with earlier cancers (T1 to T3) excepting tongue cancer. The results of this retrospective study suggested that patients with advanced tumors, multi-involvement of the ipsilateral neck nodes, or a higher degree of histopathological grading were at a higher risk for C-LNM.

Histopathological characteristics of malignant melanoma affecting mucous membranes: a unifying concept of histogenesis.

AIMS: To investigate histopathological characteristics of melanocytic lesions affecting mucous membranes in various anatomical sites. Particular attention was paid to elucidation of morphological characteristics of early phases of mucosal melanoma in order to contribute to effective detection of this highly malignant neoplasm in the curable stages. METHODS: A total of 87 melanocytic lesions of mucous membranes were investigated histopathologically. There were 55 malignant melanomas including eight lesions of melanoma in situ, three in the radial growth phase (RGP) and 44 in the vertical growth phase (VGP), and 28 benign melanocytic lesions including four melanotic macules, 19 melanocytic naevi and five blue naevi. In addition, this series also included four equivocal lesions for which diagnoses were not definitely determined. With regard to malignant melanoma, histopathological patterns of in situ phase and RGP were intensely evaluated. RESULTS: Histopathological features of benign melanocytic lesions were essentially the same as those of the corresponding lesions of the skin. In the vast majority of mucosal melanomas, irrespective of anatomical sites, the main histopathological pattern seen in melanoma in situ and in RGP was the lentiginous pattern, which shows proliferation of atypical melanocytes in the lower layer of more or less acanthotic epithelium, though subtle variations of the pattern were detected. No association of melanocytic naevus was detected in any cases of melanoma. Based on these findings, we have proposed a unifying concept of de novo histogenesis of mucosal malignant melanoma. CONCLUSIONS: Our concept of histogenesis of mucosal melanoma assists in the identification of this highly malignant neoplasm in the early curable stages.

Clinical significance of cellular distribution of moesin in patients with oral squamous cell carcinoma.

PURPOSE: Moesin is a linking protein of the submembraneous cytoskeleton and plays a key role in the control of cell morphology, adhesion, and motility. The aim of the present study was to elucidate the clinical significance of expression patterns of moesin in patients with oral squamous cell carcinoma (OSCC). EXPERIMENTAL DESIGN: Immunohistochemistry for moesin monoclonal antibody was performed on 103 paraffin-embedded specimens from patients with primary OSCC, including 30 patients with locoregional lymph node metastasis, and in the sections from nude mice transplanted with two cell lines derived from a single human tongue cancer (SQUU-A and SQUU-B). RESULTS: Expression patterns of moesin in OSCCs were divided into three groups: membranous pattern; mixed pattern; and cytoplasmic pattern. These expression patterns correlated with tumor size, lymph node metastasis, mode of invasion, differentiation, and lymphocytic infiltration. In about two-thirds of the patients with metastatic lymph node, homogeneous cytoplasmic expression was detected in the metastatic lymph nodes. In addition, SQUU-B with high metastatic potential showed more reduced levels of membrane-bound moesin than SQUU-A with low metastatic potential. A multivariate analysis demonstrated that expression patterns of moesin can be an independent prognostic factor. CONCLUSIONS: Our results suggest that moesin expression contributed to discriminating between patients with the potentiality for locoregional lymph node metastasis and those with a better prognosis and might improve the definition of suitable therapy for each.