Predictive scoring model for inferior alveolar nerve injury after lower third molar removal based on features of cone-beam computed tomography image.

INTRODUCTION: This study aimed to construct a predictive scoring system for inferior alveolar nerve injury (IANI) following lower third molar (LM3) surgery based on cone-beam computed tomography (CBCT) images. MATERIAL AND METHODS: Of the 1573 patients who underwent LM3 removal following the CBCT, 39 with IANI and 457 randomly selected patients without IANI were enrolled. We collected information regarding the demographic characteristics of the patients, surgical situations, and inferior alveolar canal (IAC)-related CBCT factors. The association with IANI-risk was evaluated with a backward stepwise logistic regression model as per the Akaike information criterion. Scoring models' abilities of discrimination (area under the curve) and calibration (Hosmer-Lemeshow test and calibration plots) were assessed, followed by evaluation of the clinical usefulness using decision curve analysis. RESULTS: As per the multivariate analysis, the coronal positioned IAC on the enlarged root (odds ratio [OR], 3.78; P = 0.001), the length of perforated IAC (>3.4 mm) (OR, 3.05; P = 0.012), lingual/inter-radicular position of the IAC (OR, 3.96; P = 0.001), multiple roots closed to the perforated IAC (OR, 2.78; P = 0.025), and age >30 y (OR, 2.31; P = 0.076) were identified in the extended scoring model ranging from 0 to 12. This model was compared with our previously constructed baseline model that involved the latter three variables mentioned above, resulting in superior performance than that of the baseline model. CONCLUSION: The extended model would be a useful tool for reliable determination of the preoperative probability of IANI.

Prognostic factors for lymph node metastasis from upper gingival carcinomas.

OBJECTIVES: This study sought to identify tumor characteristics that associate with regional lymph node metastases in squamous cell carcinomas originating in the upper gingiva. MATERIALS AND METHODS: Data from 113 patients from Osaka University Dental Hospital were included. We measured each primary tumor's width, length, depth, and the extent of bone invasion. Additionally, tumor signal intensity for T1 and T2-weighted images as well as the center of the tumor's location and T classification was assessed, and a histopathological analysis was performed. RESULTS: Tumor signal intensity was not found to be a significant prognostic factor. However, bucco-lingual width, histopathological classification as well as the tumor's location were significantly different between metastatic and non-metastatic groups in both univariate and multivariate analysis. Superior-inferior depth and T classification were significant only in the univariate (and not the multivariate) analysis. CONCLUSIONS: Bucco-lingual width, histopathological grading as well as the tumor's location are likely to be important predictors for the occurrence of LN metastasis in upper gingival carcinoma patients and should be considered when managing care for these patients.

Longitudinal study of risk for facial nerve injury in mandibular condyle fracture surgery: marginal mandibular branch-traversing classification of percutaneous approaches.

OBJECTIVE: This study aimed to longitudinally assess the risk of facial nerve injury (FNI) in the surgical repair of mandibular condylar neck and subcondylar fractures (CN/SCFs) and to explore its predictors. MATERIALS AND METHODS: In a retrospective cohort study, the outcome was defined as FNI at 1 week and 1, 3, and 6 months postoperatively. Potential predictors included age, sex, etiology, fracture site and pattern (dislocation/non-dislocation), concomitant facial fractures, interval to surgery, surgeons' experience, plate types, and the marginal mandibular branch-traversing approach (deep/superficial group). We employed generalized estimating equations (GEEs) for repeated measurements throughout the 6-month follow-up period. RESULTS: Among 102 patients with 114 fractures, 27 patients (26.5%) developed FNI within 1 week. Prolonged FNI (≥ 1 month) occurred in 19 (19.2%) of 99 patients. Multivariate GEE analyses revealed that deep surgical approaches (i.e., traditional submandibular and retroparotid approaches; odds ratio [OR], 18.90; p = 0.011), fractures with dislocation (OR, 3.60; p = 0.025), and female gender (OR, 2.71; p = 0.040) were independently associated with the overall FNI risk. Additionally, the deep approaches (OR, 15.91; p = 0.014) and female gender (OR, 3.41; p = 0.035) were correlated with a prolonged FNI risk. Sensitivity analyses for the outcomes identified the same predictors. CONCLUSION: The predictors longitudinally associated with FNI in CN/SCF surgeries included a deep MMB-traversing approach, dislocated fracture, and female gender. CLINICAL RELEVANCE: The superficial surgical approaches (i.e., transparotid, transmasseteric anteroparotid, and high perimandibular approaches) should be adopted for CN/SCF treatment to minimize postoperative morbidity, especially for female patients with dislocated condyles.

Risk stratification against inferior alveolar nerve injury after lower third molar extraction by scoring on cone-beam computed tomography image.

The study aimed to stratify the risk of inferior alveolar nerve injury (IANI) after lower third molar (LM3) surgery with a scoring system using identified predictive factors based on cone-beam computed tomography (CBCT) images. In a case-control study, the primary outcome was IANI occurrence. The control group included randomly selected patients without IANI. Predictor variables included patient demographics, surgical situations, Pell-Gregory classification, and inferior alveolar canal (IAC)-associated factors on CBCT. Study variables were analyzed using logistic regression models. Risk stratification was assessed by a scoring system that was constructed using independent predictors. The 858 patients who underwent LM3 surgery (1177 teeth) after CBCT scan were divided into case (25 patients, 2.9%, 27 teeth) and control (235 patients, 300 teeth) groups. In the multivariate model, lingual/inter-radicular position of IAC [odds ratio (OR) 7.21; P < 0.001; assigned score, 2], multiple roots closed to the IAC with cortical perforation (OR 3.72; P = 0.015; 1), and age > 30 years (OR 4.99; P = 0.008; 2) were associated with an increased IANI-risk. The IANI-risk scoring system could be stratified into low- and high-risk groups at a cutoff score of 3 (sensitivity, 68.0%; specificity, 90.6%; positive predictive value, 17.8%; positive likelihood ratio, 7.23). In conclusion, the high-risk group of IANI after LM3 surgery corresponded to individuals with multiple factors: lingual/inter-radicular IAC position to LM3, multiple roots with perforated IAC, and increased age (> 30 years). Raising awareness of the higher probability for IANI is needed for patients with multiple aforementioned factors.

Lipoma Rarely Involving Multiple Suprahyoid Fascial Spaces: A Large Lesion Removed With Bimanual Transcervical Finger Dissection Using a "Push-Pull Down" Maneuver.

Lipoma involving multiple fascial spaces is extremely rare and poses a challenge to surgeons using less invasive procedures. Although blunt dissection using a finger is often used in excisional surgeries as a supplementary maneuver, few cases have been described using the bimanual technique for the removal of these extensive lesions.Herein, the authors present a large lipoma of the oral floor extending to the unilateral submandibular and parapharyngeal spaces, which was excised only via a submandibular approach using the "push-pull down" maneuver, blunt finger dissection of the tumor with counter-pushing on the overlying mucosa to the submandibular direction facilitated tumor separation. The tumor was consequently pulled down and removed without an additional intraoral incision.Based on accurate preoperative examinations, this maneuver, provides a less invasive surgery for well-encapsulated benign tumors involving multiple fascial spaces.

[Clinicopathological Evaluation of Preoperative Chemotherapy Containing S-1 as a Treatment for Patients with Oral Squamous Cell Carcinoma during Waiting Time for Surgery].

BACKGROUND: In our department, patients with oral squamous cell carcinoma(OSCC)received preoperative chemotherapy containing S-1 to prevent the growth and dissemination of tumors during the waiting time before definitive surgery. We retrospectively evaluated the usefulness of this treatment. PATIENTS AND METHODS: One hundred and five patients comprising stages T1(26), T2(64), T3(7), and T4(8 cases)were enrolled in this study from July 2001 to June 2013. In principle, patients were administered S-1(80mg/m / 2/day, days 1-14)and followed by a drug holiday(days 15-21), continuing until 1 week before surgery. RESULTS: The median administration period was 14 days(256 days). Ninety-eight patients underwent definitive surgery, but 7 patients who revealed clinical CR underwent only biopsy and showed histological CR. The histological responses of all patients were CR(24), PR(22), and NC(59), and the response rate was 43.8%. Almost all adverse effects were Grade 1 or 2, except 1 case of neutropenia(Grade 3)and 1 case of urticaria(Grade 3). The 5-year overall survival rates were 86.7% in all cases, 95.3% in CR/PR cases, and 79.7% in NC cases. CONCLUSION: Preoperative S-1 administration during the waiting time was a safe and very effective method and was considered beneficial for patients with OSCC.

Gingival Neurofibroma With Teardrop-Shaped Defects of the Interdental Alveolar Bone: An Unusual Oral Manifestation of Neurofibromatosis Type 1.

Gingival enlargement, although frequently encountered in clinical settings, is rarely associated with systemic diseases or syndromes. Among the diverse pathological conditions of neurofibromatosis type 1 (NF-1), minor manifestations in the orofacial region are occasionally overlooked. Herein, the authors present an unusual case of gingival neurofibroma in a patient with NF-1 associated with characteristic osseous defects in the alveolus in the long-term course of 17 years from the first examination.A 5-year-old boy with NF-1 was referred for the evaluation of gingival enlargement in the posterior left maxilla. An incisal biopsy led to the diagnosis of neurofibroma. At 22 years of age, the patient was referred again with a complaint of bleeding and pain in the same region refractory to periodontal therapy. The gingiva and tuberosity were swollen, and the second molar was affected by the tumor. Radiography revealed a low level of the interdental septum beneath the tumor with a relatively intact periodontal cortical bone, exhibiting a teardrop-shaped bone defect. The lesion was completely resected with the periosteum.Gingival neurofibroma in NF-1 may be associated with osseous and dental abnormalities and can be mistaken for periodontitis. Raising awareness of this clinical entity can lead to proper management of the esthetic and functional problems in the oral and maxillofacial region.

Transcription factors related to chondrogenesis in pleomorphic adenoma of the salivary gland: a mechanism of mesenchymal tissue formation.

In salivary gland pleomorphic adenoma, expression of extracellular matrix (ECM) substances indicates that tumor epithelial cells are becoming chondrogenic and will produce cartilage-like mesenchymal tissues. Sox9, the master transcription factor of chondrogenesis, is expressed in mouse salivary gland cells. To clarify the mechanism behind chondrogenesis in tumor epithelial cells, we examined the expression of transcription factors related to chondrogenesis in tumors and salivary glands. Reverse transcriptase-polymerase chain reaction (RT-PCR), quantitative real-time RT-PCR, and immunostaining were performed on pleomorphic adenoma tissues, salivary gland tissues, and human submandibular gland (HSG) cells. The mRNAs of essential transcription factors for chondrogenesis-Sox9, Sox6, and Sox5-were detected in both tumor and salivary gland tissues. The mRNAs of aggrecan and type II collagen-cartilage-specific ECM substances-were detected only in tumors. Sox9 and Sox6 proteins were colocalized in many epithelial cells in tumors and salivary glands. Tumor epithelial cells also possessed aggrecan protein and occasionally type II collagen protein. Moreover, mRNAs for transcription repressors of chondrogenesis δEF1 and AP-2α were detected in both tumors and salivary glands, whereas Twist1 mRNA was detected only in salivary glands and was at significantly low-to-undetectable levels in tumors. Twist1 protein was localized in the Sox9-expressing salivary gland cells. HSG cells expressed Sox9, Sox6, and Twist1, but not aggrecan or type II collagen, and thus were similar to salivary gland cells. Twist1 depletion by Twist1 siRNA led to the upregulation of aggrecan and type II collagen mRNA expression in HSG cells. In contrast, forced expression of Twist1, using Twist1 cDNA, resulted in the downregulation of both these genes. Taken together, these results indicate that salivary gland cells have a potential for chondrogenesis, and Twist1 depletion concomitant with neoplastic transformation, which would permit tumor epithelial cells to produce cartilage-like mesenchymal tissues in salivary gland pleomorphic adenoma.

Sonoporation as an enhancing method for boron neutron capture therapy for squamous cell carcinomas.

BACKGROUND: Boron neutron capture therapy (BNCT) is a selective radiotherapy that is dependent on the accumulation of ¹°B compound in tumors. Low-intensity ultrasound produces a transient pore on cell membranes, sonoporation, which enables extracellular materials to enter cells. The effect of sonoporation on BNCT was examined in oral squamous cell carcinoma (SCC) xenografts in nude mice. MATERIALS AND METHODS: Tumor-bearing mice were administrated boronophenylalanine (BPA) or boronocaptate sodium (BSH) intraperitoneally. Two hours later, tumors were subjected to sonoporation using microbubbles followed by neutron irradiation. RESULTS: The ¹°B concentration was higher in tumors treated with sonoporation than in untreated tumors, although the difference was not significant in BPA. When tumors in mice that received BPA intraperitoneally were treated with sonoporation followed by exposure to thermal neutrons, tumor volume was markedly reduced and the survival rate was prolonged. Such enhancements by sonoporation were not observed in mice treated with BSH-mediated BNCT. CONCLUSIONS: These results indicate that sonoporation enhances the efficiency of BPA-mediated BNCT for oral SCC. Sonoporation may modulate the microlocalization of BPA and BSH in tumors and increase their intracellular levels.

Nodular fasciitis in the buccal region with rapid growth after incisional biopsy mimicking sarcoma.

Nodular fasciitis (NF) is a reactive and proliferative fibroblastic lesion that occurs predominantly in the upper limbs but rarely develops in the oral cavity. This lesion can be misdiagnosed as malignant owing to its frequent display of rapid growth, rich cellularity, and high mitotic activity. Unlike a sarcoma, NF can resolve spontaneously or after an incisional biopsy. We describe a challenging case involving a lesion in the buccal region that rapidly enlarged after incisional biopsy. This variation of clinical behavior illustrates the difficulty in predicting whether NF will continue to grow or regress. Clinicians dealing with cases of an enlarging fibrous lesion of short duration should remain aware of this disease entity and its potential diagnostic dilemma.

Lymphatic vessels and related factors in adenoid cystic carcinoma of the salivary gland.

Adenoid cystic carcinoma of the salivary gland preferentially metastasizes to distant organs. It rarely metastasizes to lymph nodes. Recently, lymphangiogenesis has been associated with lymph node metastasis. Therefore, lymphangiogenesis in adenoid cystic carcinoma was evaluated from the number of lymphatic vessels and the expression of lymphangiogenic factors. Immunohistochemistry and molecular analysis were performed on clinical materials (29 cases for immunohistochemistry and 9 cases for molecular analysis). Normal submandibular gland was used as a negative control of lymphangiogenesis (10 cases for immunohistochemistry and 5 cases for molecular analysis). In adenoid cystic carcinoma, podoplanin-positive lymphatic vessels were small and often constricted, and localized to the tumor periphery. They did not have Ki67-positive endothelial cells. The lymphatic vessel density of the tumor did not exceed that of the salivary gland. By reverse transcriptase-polymerase chain reaction, adenoid cystic carcinoma and the salivary gland expressed vascular endothelial growth factor receptor-3 (VEGFR-3) similarly but VEGF-C and VEGF-D differently. Adenoid cystic carcinoma expressed VEGF-C, whereas the salivary gland expressed both VEGF-C and VEGF-D. VEGF-C was weak in adenoid cystic carcinoma and strong in the salivary gland. Real-time reverse transcriptase-polymerase chain reaction of VEGF-C showed that the ratio of the tumor to the salivary gland was 1 to 30 (P<0.01). Immunohistochemistry barely detected VEGF-C in adenoid cystic carcinoma. VEGF-C was expressed faintly by the tumor cells. VEGF-C and VEGF-D were detected in the serous acinar and duct cells and in the duct contents in the salivary gland. VEGFR-3 appeared to be expressed by lymphatic vessels in both adenoid cystic carcinoma and the salivary gland. These results indicate that lymphangiogenesis does not occur in adenoid cystic carcinoma. This condition would lead to the uncommon lymphatic metastasis.

Effectiveness of boron neutron capture therapy for recurrent head and neck malignancies.

It is necessary to explore new treatments for recurrent head and neck malignancies (HNM) to avoid severe impairment of oro-facial structures and functions. Boron neutron capture therapy (BNCT) is tumor-cell targeted radiotherapy that has significant superiority over conventional radiotherapies in principle. We have treated with BNCT 42 times for 26 patients (19 squamous cell carcinomas (SCC), 4 salivary gland carcinomas and 3 sarcomas) with a recurrent and far advanced HNM since 2001. Results of (1) (10)B concentration of tumor/normal tissue ratios (T/N ratio) of FBPA-PET studies were SCC: 1.8-5.7, sarcoma: 2.5-4.0, parotid tumor: 2.5-3.7. (2) Therapeutic effects were CR: 12 cases, PR: 10 cases, PD: 3 cases NE (not evaluated): 1 case. Response rate was 85%. (3) Improvement of QOL such as a relief of severe pain, bleeding, and exudates at the local lesion, improvement of PS, disappearance of ulceration, covered with normal skin and preserved oral and maxillofacial functions and tissues. (4) Survival periods after BNCT were 1-72 months (mean: 13.6 months). Six-year survival rate was 24% by Kaplan-Meier analysis. (5) Adverse-events were transient mucositis and alopecia in most of the cases; three osteomyelitis and one brain necrosis were recognized. These results indicate that BNCT represents a new and promising treatment approach for advanced HNM.

Benign fibrous histiocytoma in the condylar process of the mandible: Case report.

A 48-year-old man was referred for investigation of an asymptomatic radiolucent lesion in the mandible. The margin was partly irregular, and there was no peripheral sclerosis. The tumour was composed of histiocytic cells, spindle cells, and fibrous tissue. Immunohistochemical analysis showed that the tumour cells stained for CD68 and vimentin, and not for cytokeratin, smooth muscle actin, S-100 protein, or CD34. The tumour was therefore diagnosed as a benign fibrous histiocytoma.

[Preoperative chemotherapy with S-1 and low-dose cisplatin for oral squamous cell carcinoma].

We investigated preoperative chemotherapy with S-1 and low-dose cisplatin for the untreated stage II-IV oral squamous cell carcinoma patients. The chemotherapy consisted of S-1 80 mg/m2/day (day 1-14) and CDDP 5 mg/m2/day (day 1-5 and day 8-12) intravenous drip (less than 1 hour). In the second phase clinical trial of 44 patients, the clinical response rate was 63.7% and the histological response rate by the Oboshi-Shimosato's evaluation was 61.4%. The main adverse events were myelosuppression and gastrointestinal disturbance such as nausea 36.4%, anorexia 27.3%, neutropenia 25% and leukopenia 25%. Grade 3 and 4 adverse events were neutropenia 11.4%, leukopenia 9.1%, thrombocytopenia 4.5% and oligochromemia 4.5%. The two-year overall survival rate was 92.6%. The advantages of this chemotherapy are high response rate, low adverse effects and not to prevent planned therapies such as surgery and radiation. These facts suggest that this chemotherapy is suitable for preoperative chemotherapy.

Mutations of the APC, beta-catenin, and axin 1 genes and cytoplasmic accumulation of beta-catenin in oral squamous cell carcinoma.

PURPOSE: The Wnt pathway is involved in carcinogenesis and three regulatory genes of the Wnt pathway, APC, beta-catenin and Axin are mutated in some primary human cancers. Mutations in these genes can impair the down regulation of beta-catenin, which results in the stabilization of beta-catenin, accumulation of free beta-catenin and subsequent activation of the Wnt pathway. To clarify the genetic alterations of components of the Wnt pathway in oral squamous cell carcinoma (SCC), we examined mutations in the APC, beta-catenin and Axin genes and subcellular localization of beta-catenin. METHODS: 20 oral SCC tissues and four cell lines derived from oral SCC were used. Mutational analysis was performed by a single-strand conformation polymorphism (SSCP) method and direct sequencing analysis. The samples were also examined by immunohistochemical staining and immunoblot analysis. RESULTS: In 3 of 4 cell lines, mutations were observed in the APC and Axin1 genes without amino acid substitutions. In a clinical sample, a mutation in the Axin1 gene was detected; a T insertion at codon 250 resulted in the formation of a stop codon at codon 259. In addition, cytoplasmic accumulation of beta-catenin was observed in 3 (75%) of 4 cell lines and 18 (90%) of 20 cancer tissue samples. CONCLUSION: The Axin1 gene may be one of the mutational target in oral SCC. In addition, the cytoplasmic accumulation of beta-catenin is a common characteristic of oral SCC, but is not closely associated with mutational alterations in the APC, beta-catenin and Axin1 genes.

[Preoperative chemotherapy with TS-1 and low dose cisplatin for oral squamous cell carcinoma patients--a preliminary study].

We investigated the histological response and toxicities of combination chemotherapy with TS-1 and low-dose CDDP, and evaluated the usefulness of this regimen as a preoperative chemotherapy. Fourteen patients were enrolled in this study (two men and 12 women, with a mean age of 54.5 years). Patients were administered TS-1 80 mg/m2/day (days 1-14) and CDDP 5 mg/m2/day (days 1-5, 8-12) and followed by radical surgery or biopsy within 2 weeks. Ten patients completed 1 cycle of chemotherapy, two received 0.5 cycle and two others 1.5 cycle. The histological antitumor effects were evaluated with Ohboshi & Shimosato's classification using surgical or biopsy specimens of primary tumors. The response rate was 64.3% in clinical evaluation and 50.0% in histological evaluation. The number of patients who showed CR were 7/14 (50.0%) and 5/14 (35.7%) by histological and clinical evaluation, respectively. Two patients showed grade 3 neutropenia. Almost all patients revealed no or mild toxicities. TS-1 with low-dose CDDP represents a highly effective antitumor activity and mild toxicities. Especially, the CR rate was very high. These data suggested that this regimen was useful to avoid surgery or to realize minimal surgery for oral squamous cell carcinoma patients.

Anti-HER-2/neu immune responses are induced before the development of clinical tumors but declined following tumorigenesis in HER-2/neu transgenic mice.

HER-2/neu oncogene products have been implicated as a potential target of T cell-mediated immune responses to HER-2/neu-induced tumors. Using HER-2/neu transgenic mice (oncomice), we investigated whether, and if so how, anti-HER-2/neu immune responses are induced and modulated in these oncomice from birth to tumor initiation. Female oncomice carrying the activated HER-2/neu oncogene displayed apparent hyperplasia in mammary glands at 10 weeks of age and developed mammary carcinomas around an average age of 26 weeks. Unfractionated spleen cells from 10- to 15-week-old oncomice that were cultured without any exogenous stimuli exhibited cytotoxicity against the F31 tumor cell line established from an HER-2/neu-induced mammary carcinoma mass. The final antitumor effectors were a macrophage lineage of cells. However, this effector population was activated, depending on the stimulation of oncomouse CD4(+) T cells with oncomouse-derived antigen-presenting cell (APC) alone or with wild-type mouse APC in the presence of F31 membrane fractions, suggesting the presence of HER-2/neu-primed CD4(+) T cells and HER-2/neu-presenting APC in 10- to 15-week-old oncomice. These antitumor cytotoxic responses were detected at approximately 5 weeks of age and peaked at age 10 to 15 weeks. However, the responses then declined at tumor-bearing stages in which the expression of target proteins could progressively increase. This resulted from the dysfunction of CD4(+) T cells but not of APC or effector macrophages. These results indicate that an anti-HER-2/neu CD4(+) T cell-mediated immune response was generated at the pretumorigenic stage but did not prevent tumorigenesis and declined after the development of clinical tumors.