Lower Lip Cancer Managed by Reconstruction with a Double Abbe Flap - A Case Report.

Although the incidence of lower lip cancer is not high in Japan, its treatment requires an approach that considers both esthetics and function. When surgical resection is required, the method used for reconstruction varies depending on the affected part. Despite various studies proposing different types of algorithms, no single method is considered the best. If the loss of half or more of the lip is predicted, a free flap may need to be considered, depending on the case. Here, we report a case involving a 78-year-old edentulous woman with lower lip cancer whose resection area involved approximately 70% of the red and white portions of the lower lip. Fortunately, no resection was required at the commissure. We accordingly performed reconstruction with a double Abbe flap in accordance with a detailed treatment plan. The patient was extremely satisfied with the esthetic and functional outcomes of the surgery.

Identifying Differences Between a Straight Face and a Posed Smile Using the Homologous Modeling Technique and the Principal Component Analysis.

Recently, a homologous modeling method was developed to simulate 3D human body forms, which can visualize principal component analysis (PCA) results and facilitate its detailed comparison with results of previous method. Herein, we aimed to construct a homologous model of the face to identify differences between a straight face and a posed smile. Thirty-eight volunteers (19 males and 19 females, 38 straight faces and 38 posed smiles) with no medical history associated with a posed smile were enrolled. Three-dimensional images were constructed using the Homologous Body Modeling software and the HBM-Rugle; 9 landmarks were identified on the 3D-model surfaces. The template model automatically fitted into an individually scanned point cloud of the face by minimizing external and internal energy functions. Faces were analyzed using PCA; differences between straight faces and posed smiles were analyzed using paired t tests. Contribution of the most important principal component was 23.8%; 8 principal components explained >75% of the total variance. A significant difference between a straight face and a posed smile was observed in the second and the fourth principal components. The second principal component images revealed differences between a straight face and a posed smile and changes around the chin area with regard to length, shape, and anteroposterior position. Such changes were inclusive of individual differences. However, the fourth principal component image only revealed differences between a straight face and a posed smile; observed differences included simultaneous shortening of upper and lower eyelid length, evaluation of the nasal ala ase, swelling of the cheek area, and elevation of the mouth angle. Although these results were clinically apparent, we believe that this article is the first to statistically verify the same.Consequently, the homologous model technique and PCA are useful for evaluation of the facial soft-tissue changes.

Beckwith-Wiedemann syndrome with asymmetric mosaic of paternal disomy causing hemihyperplasia.

Beckwith-Wiedemann syndrome (BWS) is a congenital disorder with 3 main features-overgrowth in infancy, macroglossia, and abdominal wall defects. Here, we report on a 5-month old girl with hemihyperplasia and macroglossia caused by paternal uniparental disomy (pUPD) asymmetric mosaic on chromosome 11p15.5. She could not retract her tongue into her mouth and the midline of the tongue was shifted to the left. Glossectomy was performed at age 1 year. A specimen of the tongue showed normal skeletal muscle, but the muscle fibers were closely spaced, and there were fewer stroma components in the tissue from the right side of the tongue than that from the left side. With respect to pUPD of chromosome 11p15.5, microsatellite marker analysis of the tongue tissue specimen revealed a higher mosaic rate in the tissue from the right side of the tongue (average 48.3%) than that from the left side (average 16.9%). Methylation analysis of Kv differentially methylated region (DMR) 1 (KvDMR1) and H19DMR revealed hypomethylation of KvDMR1 and hypermethylation of H19DMR in the tissue on the right side of the tongue (hyperplastic side). In this case, the difference in mosaic rate of pUPD in the 11p15.5 region was hypothesized to influence the expression level of insulin-like growth factor 2. This result may be helpful to clinicians, especially surgeons, when planning plastic surgery for hemihyperplasia.

Osteosynthesis Using the Uncalcined and Unsintered Hydroxyapatite / Poly-L-Lactic Acid System.

The poly-L-lactic acid mini-plate system accomplished rapid development. However, the system still has a variety of problems. One such problem is the breakage of screws. In this technical report, we develop the temporary fixing screws made from stainless with hexagon steel that exhibit a hexagonal head and thread part that also features a tapping function.

Mandibular central leiomyosarcoma with high telomerase activity: a case report.

Leiomyosarcoma is a malignant lesion of smooth muscle origin, and rare in the oral region. This report presents an extremely rare case of intraosseous leiomyosarcoma of the mandible. After visiting other general hospital, a 29-year-old man was referred to our hospital because of a pain in the left mandibular region with paresthesia of the left mental region. The left mandibular third molar had already been extracted in another hospital, and a brownish mass occupied the corresponding region. A panoramic radiograph showed osteolytic destruction around the left mandibular angle and ramus. A computed tomography scan and magnetic resonance image revealed perforation of the lingual and buccal cortex of the mandible. A non-epithelial malignant tumor was diagnosed from a biopsy specimen. Immediately, we resected the tumor and reconstructed the titan plate under general anesthesia. A final diagnosis of leiomyosarcoma was made from a surgical specimen based on findings showing a proliferation of hyperchromatic spindle cells, which were positive for the markers α- smooth muscle actin, calponin, HHF35, and desmin. The S-100, epithelial membrane antigen, and cytokeratin markers were negative. The patient had 3 courses of adjuvant chemotherapy after the operation, and showed no evidence of recurrence during the follow-up at the outpatient clinic. However, 2 years after the first operation, lung metastases and local recurrence were detected. Additional chemotherapy was not effective. Finally, the patient died almost 3 years after the first operation.

Regulation of ß-Catenin Phosphorylation by PR55ß in Adenoid Cystic Carcinoma.

BACKGROUND/AIM: Adenoid cystic carcinoma (AdCC) is a rare cancer of the salivary gland with high risk of recurrence and metastasis. Wnt signalling is critical for determining tumor grade in AdCC, as it regulates invasion and migration. ß-catenin dephosphorylation plays an important role in the Wnt pathway, but its underlying molecular mechanism remains unclear. MATERIALS AND METHODS: Because the regulatory subunits of protein phosphatase 2A (PP2A) drive Wnt signalling via target molecules, including ß-catenin, we used qRT-PCR and immunoblot analysis to investigate the expression of these subunits in an AdCC cell line (ACCS) and a more aggressive subline (ACCS-M). RESULTS: PR55ß was highly expressed in ACCS-M, suggesting its functional importance. In addition, PR55ß expression was associated with tumor grade, with ACCS-M exhibiting higher PR55ß levels. More importantly, knockdown of PR55ß in ACCS-M cells significantly reduced invasiveness and metastatic ability. Furthermore, dephosphorylation and total levels of ß-catenin were dependent on PR55ß in ACCS-M. Finally, we confirmed a correlation between PR55ß staining intensity and histopathological type in human AdCC tissues. CONCLUSION: Our study provides new insight into the interaction between PR55ß and ß-catenin and suggests that PR55ß may be a target for the clinical treatment of AdCC.

Deregulation of Nicotinamide N-Methyltransferase and Gap Junction Protein Alpha-1 Causes Metastasis in Adenoid Cystic Carcinoma.

BACKGROUND/AIM: Adenoid cystic carcinoma (AdCC) is a malignant tumor that occurs in the salivary glands and frequently metastasizes. The aim of this study was to identify factors mediating AdCC metastasis. MATERIALS AND METHODS: We established three AdCC cell lines by orthotropic transplantation and in vivo selection: parental, highly metastatic (ACCS-M-GFP), and lymph node metastatic (ACCS-LN-GFP) cells. RESULTS: We examined the three cell lines. DNA microarray indicated significantly altered processes in ACCS-LN-GFP cells: particularly, the expression of nicotinamide N-methyltransferase (NNMT) was enhanced the most. NNMT is associated with tumorigenesis and is a potential tumor biomarker. Concomitantly, we found-significant down-regulation of gap junction protein alpha-1. We suggest that ACCS-LN-GFP cells acquire cancer stem cell features involving the up-regulation of NNMT and the loss of gap junction protein alpha-1, leading to epithelial-mesenchymal transition and consequent AdCC metastasis. CONCLUSION: NNMT is a potential biomarker of AdCC.

The relationship between lateral displacement of the mandible and scoliosis.

OBJECTIVES: Idiopathic scoliosis is an orthopaedic disease of childhood, with onset and progress occurring until adolescence. Here, the relationship between lateral displacement of the mandible and scoliosis was analysed quantitatively. METHODS: Seventy-nine non-syndromic Japanese patients (18 men, 61 women), who were diagnosed with jaw deformities and underwent surgical orthognathic treatment at Kyushu University Hospital from January 2011 to August 2014, were enrolled. Their mean age at the time of radiography was 25.3 ± 8.7 years. Postero-anterior cephalometric radiographs and chest radiographs were examined. In postero-anterior cephalometric radiographs, a horizontal baseline (X-axis) was drawn as a straight line that intersects both the zygomatic bases, and a vertical line (Y-axis) was marked perpendicular to the X-axis, with an intersection at the anterior nasal spine (ANS). Point A was defined as the intersection of the X- and Y-axes, and line A was defined as the line connecting point A to the menton. The angle made by the X-axis and line A (i.e., lateral displacement of the mandible) was measured. We designated an absolute value even if the mandibular menton was located on the right or left side. In chest radiographs, Cobb's method was used to measure scoliosis curves; the direction of the curve was designated similarly. RESULTS: Nine (11.4%) individuals had a Cobb angle >10°. There was a positive correlation between the Cobb angle and the degree of mandibular deviation (p < 0.05). CONCLUSION: Lateral displacement of the mandible and scoliosis are related.

Introduction of ID2 Enhances Invasiveness in ID2-null Oral Squamous Cell Carcinoma Cells via the SNAIL Axis.

AIM: Inhibitor of DNA-binding (ID) proteins are negative regulators of basic helix-loop-helix transcription factors that generally stimulate cell proliferation and inhibit differentiation. However, the role of ID2 in cancer progression remains ambiguous. Here, we investigated the function of ID2 in ID2-null oral squamous cell carcinoma (OSCC) cells. MATERIALS AND METHODS: We introduced an ID2 cDNA construct into ID2-null OSCC cells and compared them with empty-vector-transfected cells in terms of cell proliferation, invasion, and activity and expression of matrix metalloproteinase (MMP). RESULTS: ID2 introduction resulted in enhanced malignant phenotypes. The ID2-expressing cells showed increased N-cadherin, vimentin, and E-cadherin expression and epithelial-mesenchymal transition. In addition, cell invasion drastically increased with increased expression and activity of MMP2. Immunoprecipitation revealed a direct interaction between ID2 and zinc finger transcription factor, snail family transcriptional repressor 1 (SNAIL1). CONCLUSION: ID2 expression triggered a malignant phenotype, especially of invasive properties, through the ID2-SNAIL axis. Thus, ID2 represents a potential therapeutic target for OSCC.

Blockade of Androgen-induced Malignant Phenotypes by Flutamide Administration in Human Salivary Duct Carcinoma Cells.

BACKGROUND/AIM: Androgens are known to play a critical role in prostate cancer progression, but their effect on malignant phenotypes in salivary gland cancer is unclear. The androgen-androgen receptor (AR) axis may be involved in malignant phenotypes of salivary duct carcinoma (SDC) cells and therefore may be a new target for SDC treatment. To test this hypothesis, we investigated the effect of the androgen 5α-dihydrotestosterone (DHT) on proliferation, migration, and invasiveness of SDC cells. MATERIALS AND METHODS: We used a wound-healing assay to measure cell migration and a Boyden chamber invasion assay to investigate SDC cell invasive capacity. RESULTS: DHT treatment increased cell proliferation, migration, and invasion. However, treatment with flutamide, an AR inhibitor, blocked the effects of DHT. CONCLUSION: These results suggest that the androgen-AR axis is involved in SDC malignancy and may be an effective therapeutic target for treatment of human SDC.

Targeting ID2 expression triggers a more differentiated phenotype and reduces aggressiveness in human salivary gland cancer cells.

Inhibitors of DNA-binding (ID) proteins are negative regulators of basic helix-loop-helix transcription factors and generally stimulate cell proliferation and inhibit differentiation. We previously determined that ID1 was highly expressed in aggressive salivary gland cancer (SGC) cells in culture. Here, we show that ID2 is also expressed in aggressive SGC cells. ID2 knockdown triggers important changes in cell behavior, that is, it significantly reduces the expression of N-cadherin, vimentin and Snail, induces E-cadherin expression and leads to a more differentiated phenotype exemplified by changes in cell shape. Moreover, ID2 knockdown almost completely suppresses invasion and the expression of matrix metalloproteinase 9. In conclusion, ID2 expression maintains an aggressive phenotype in SGC cells, and ID2 repression triggers a reduction in cell aggressiveness. ID2 therefore represents a potential therapeutic target during SGC progression. ID proteins are negative regulators of basic helix-loop-helix transcription factors and generally stimulate cell proliferation and inhibit differentiation. ID2 knockdown triggers important changes in cell behavior, that is, it significantly reduces the expression of N-cadherin, vimentin and Snail, induces E-cadherin expression and leads to a more differentiated phenotype exemplified by changes in cell shape. ID2 therefore represents a potential therapeutic target during SGC progression.

Stimulation of the Estrogen Axis Induces Epithelial-Mesenchymal Transition in Human Salivary Cancer cells.

BACKGROUND: Salivary gland cancer is a common type of head and neck cancer characterized by occasional deep invasion and lung metastasis. The precise role of sex steroid hormones in salivary gland cancer is unclear. To address this issue, we investigated whether the estrogen axis modulates salivary adenocarcinoma (SAC) and whether hormone therapy can be an effective treatment. MATERIALS AND METHODS: The estrogen receptor (ER) was overexpressed in HSG human SAC cells that lack endogenous ER and the cells were treated with and without 17ß-estradiol (E2). RESULTS: E2 enhanced malignant phenotypes. Moreover, E2 treatment reduced E-cadherin expression, while increasing that of N-cadherin, vimentin, and inhibitor of differentiation 1 proteins that are associated with the epithelial-mesenchymal transition. Cell invasion was enhanced through activation of matrix metalloproteinase-9. CONCLUSION: These results indicate that hormone therapy used in breast cancer may also be effective for ER-positive SAC.

ID1 Controls Aggressiveness of Salivary Gland Cancer Cells via Crosstalk of IGF and AKT Pathways.

BACKGROUND: Inhibitor of differentiation or DNA binding 1 (ID1) is overexpressed in human salivary gland cancer (SGC). The insulin growth factor (IGF) system is an attractive target in cancer control because it is associated with various cancer progressions. MATERIALS AND METHODS: The human SGC cell line HSY with abundant ID1 was used. ID1 knockdown and its effect on the IGF system were investigated. Cell proliferation and invasion, as well as associated protein expression, were analyzed. Phospho-AKT was also evaluated. RESULTS: ID1 knockdown reduced cell proliferation and invasion, while the expression of proteins associated with malignant phenotypes was altered. IGF-II expression was suppressed, suggesting that this system is one of the mechanisms underlying effects of ID1 in SGC cells. c-Myc was up-regulated, whereas p21 and p27 were down-regulated. Moreover, phospho-AKT was reduced in ID1-knockeddown cells. CONCLUSION: ID1 down-regulation induced parallel changes in the IGF and AKT pathways. The crosstalk of these pathways may enhance malignant phenotypes in SGCs.

Bite Force and Masticatory Performance Using Implant-supported Overdentures After Treatment of Mandibular Cancer.

AIM: To evaluate overdentures with regard to artificial restoration of oral function following mandibular cancer. MATERIALS AND METHODS: We examined 32 patients who had undergone mandibular bone resection as treatment for malignancy and were using implant-supported overdentures. The patients were aged 55-87 years (mean=68.6) with a male to female ratio of 23:9. Marginal resection was performed in 29 patients and segmentectomy in 3. RESULTS: Before and after using the attachment for overdenture, oral function differed significantly. After the setting of implant-retained overdentures, maximum bite force increased on average by 362% (average, from 16.2 N to 58.8 N; p<0.01). Xylitol gum examination showed a 363% increase in masticatory performance (average, 3.1 to 8.0 points; p<0.01). CONCLUSION: Implant-retained overdenture resulted in improved oral function, that was lost after treatment for mandibular cancer.

Estrogen Enhances Malignant Phenotypes in Human Salivary Adenoid Cystic Carcinoma Cells.

BACKGROUND/AIM: Adenoid cystic carcinoma (SGC) is a common type of salivary gland cancer (SGC). Surgery is the first treatment choice because chemoradiotherapy is usually not effective. Therefore, new treatment modalities are urgently needed. In this study, it was investigated whether the estrogen axis could be a treatment target or not. MATERIALS AND METHODS: Adenoid cystic carcinoma (ACC) ACCM cells, were used. The specific cell line lacks estrogen receptor (ER). ER was introduced in ACCM cells, and the effect of 17ß-estradiol (E2) was investigated on cell proliferation, cell-cycle distribution, and cell motility. RESULTS: E2 induced cell proliferation, and the S-phase fraction increased in a dose-dependent manner. Cell motility was also up-regulated compared to control cells. CONCLUSION: The estrogen/ER system up-regulated malignant phenotypes in ER-positive ACC, and hormone therapy may have a potential as effective treatment for this malignancy.

The Contribution of Dental Implants to Functional Artificial Restoration After Treatment of Oral Cancer.

BACKGROUND/AIM: The aim of this study was to evaluate dental implants with regard to artificial restoration of oral function and quality of life in patients with oral cancer. PATIENTS AND METHODS: We examined 134 implants in 41 patients who had undergone jawbone resection as treatment for oral cancer. The patients were aged 44-89 (mean=61.5) years, and the male to female ratio was 27:14. RESULTS: The 5-year implant success rate was 91.0%. Of the 12 unsuccessful implants, four were embedded on bone grafts with skin flaps, four were embedded on skin flaps using muscle, and four were embedded after peripheral resection. Of the 41 patients, 11 received radiation, but exposure to radiation was not associated with implant loss. The level of satisfaction on the visual analog scale before development of oral cancer was set at 100 mm. Satisfaction fell to 47.0 mm after primary treatment, but recovered to 82.6 mm after implant therapy. CONCLUSION: Patient satisfaction after implant therapy was high, and the implants resulted in improved quality of life. A high proportion of cases involving use of skin flaps resulted in implant loss. Constructing an immobile mucous membrane by replacement of a skin flap with a skin graft may facilitate self-maintenance of implants.

High Le Fort I osteotomy for correction of mid-face deformity in Crouzon syndrome.

An 18-year-old woman with mild Crouzon syndrome was referred with malocclusion and mandibular protrusion. Examination revealed Class III canine and molar relationships, hypoplastic maxilla, 1-mm overbite, and -2-mm overjet. Analysis showed 69° sella-nasion-A, 73.6° sella-nasion-B, and -4.6° A point-nasion-B point angles. Polysomnography revealed respiratory disturbance and 6.3% oxygen desaturation indices of 5.4/h and 9.0/h. We performed double-jaw surgery using high Le Fort I osteotomy and bilateral sagittal split ramus osteotomy for midfacial deformity correction. Twelve months post-surgery, her measures were 70.8°, 72°, -1.2°, 3.0/h, and 6.1/h, respectively. Esthetics were satisfactory. High Le Fort I osteotomy is effective for midfacial deformity correction in patients with Crouzon syndrome.

Suppression of invasion and metastasis in aggressive salivary cancer cells through targeted inhibition of ID1 gene expression.

Salivary gland cancer (SGC) represents the most common malignancy in the head and neck region, and often metastasizes to the lungs. The helix-loop-helix ID1 protein has been shown to control metastatic progression in many types of cancers. Using two different approaches to target the expression of ID1 (genetic knockdown and progesterone receptor introduction combined with progesterone treatment), we previously determined that the aggressiveness of salivary gland tumor ACCM cells in culture was suppressed. Here, using the same approaches to target ID1 expression, we investigated the ability of ACCM cells to generate lung metastatic foci in nude mice. Moreover, since both approaches would be challenging for applications in humans, we added a third approach, i.e., treatment of mice with a non-toxic cannabinoid compound known to down-regulate ID1 gene expression. All approaches aimed at targeting the pro-metastatic ID1 gene led to a significant reduction in the formation of lung metastatic foci. Therefore, targeting a key transcriptional regulator using different means results in the same reduction of the metastatic spread of SGC cells in animal models, suggesting a novel approach for the treatment of patients with aggressive SGC.

Objective validity of an implant-retained overdenture with a ball attachment system after marginal mandibulectomy.

Implant-retained overdentures are known to improve oral function, but the clinical impact on patients who have had mandibular resections is still debatable. We have treated 16 patients who had such resections for oral cancer and consequent loss of the alveolar ridge, with overdentures supported by osseointegrated implants and ball attachments. To quantify their functional improvement, we evaluated their maximum bite force and masticatory performance. Their function improved significantly, (from 77.5N - 365N, 371% increase in maximum bite force, p<0.001) and masticatory performance increased (from 2.5 - 7.7, 208%, p<0.0001) after the overdentures had been inserted. While individual changes in maximum bite force showed no significant correlation, those in masticatory performance correlated significantly, which suggests that the subjects with poor masticatory function are likely to benefit from retention of an implant. These results indicate that implant-retained overdentures are an effective way to rehabilitate patients after marginal mandibular resection.

Custom-made titanium devices as membranes for bone augmentation in implant treatment: Clinical application and the comparison with conventional titanium mesh.

OBJECTIVE: Development of new custom-made devices to reconstruct alveolar bone for implantation, and comparison with conventional methods were the goals of this study. MATERIALS AND METHODS: Using a computer-aided design technique, three-dimensional images were constructed. From these data, custom-made devices were produced by a selective laser melting method with pure titanium. Clinical trials also have been conducted with 26 participants who needed bone reconstruction before implantation; they were divided into 2 groups with 13 patients each. The first group uses custom-made devices; the other uses commercial titanium meshes that need to bend during operation. Some clinical aspects are evaluated after the trial. RESULTS: The custom-made devices can be produced closely by following the data precisely. Devices are fit for bone defect site. Moreover, the operation time of the custom-made group (75.4 ± 11.6 min) was significantly shorter than that of the conventional group (111.9 ± 17.8 min) (p < 0.01). Mucosal rupture occurs, without significant difference (p = 0.27), in a patient in the custom-made without severe infection (7.7%), and 3 in conventional (23.1%), respectively. The retaining screw is significantly fewer in the custom-made group than commercial mesh group (p < 0.01). CONCLUSION: These results indicate that our novel protocol could be simple and safe for providing powerful support for guided bone regeneration.