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Summary Objectives When treating advanced HNSCC, a cisplatin-based systemic regimen benefit patient survival. However, chemoresistance will greatly reduce the effectiveness of this approach. The identification of molecules that contribute to cisplatin resistance may potentially improve the survival. Both HB-EGF and COX-2 have been reported to increase cisplatin-resistance. Here, we have focused on the regulation of HB-EGF/COX-2 and their roles in cisplatin resistance. Materials and Methods IHC staining was used to measure the expression levels of HB-EGF and COX-2 on the tissue microarray from 43 tissue samples of patients with advanced HNSCC. siRNA, western blot and qRT-PCR were used to dissect the regulation between EGF, Akt, COX-2, PGE2, and cisplatin sensitivity. The correlation between HB-EGF, COX2 and HNSCC progression was analyzed by the receiver operating characteristic (ROC) curve and Kaplan–Meier disease free survival. Results Patients of advanced HNSCC patients with increased HB-EGF and COX-2 expression have higher tumor recurrent rates that was related to cisplatin resistance. The resistance was mediated via an increased expression of HB-EGF and COX-2. The activation of Akt by either EGF or areca nut extract were able to upregulate COX-2, which would increase the expression of HB-EGF in a PGE2 dependent manner. Inhibition and knockdown of COX-2 resulted in a decrease in HB-EGF. In the tissue samples from HNSCC patients, there was a significant positive correlation between the expression of COX-2 and HB-EGF. Conclusion Our results suggested that COX-2 and HB-EGF are important in development of HNSCC cisplatin resistance. These findings may help the development of new strategies for overcoming cisplatin resistance.

Purpose To investigate the efficacy and safety of fractionated boron neutron capture therapy (BNCT) for recurrent head and neck (H&N) cancer after photon radiation therapy. Methods and Materials In this prospective phase 1/2 trial, 2-fraction BNCT with intravenous L-boronophenylalanine (L-BPA, 400 mg/kg) was administered at a 28-day interval. Before each fraction, fluorine-18-labeled-BPA–positron emission tomography was conducted to determine the tumor/normal tissue ratio of an individual tumor. The prescription dose (D80) of 20 Gy-Eq per fraction was selected to cover 80% of the gross tumor volume by using a dose volume histogram, while minimizing the volume of oral mucosa receiving >10 Gy-Eq. Tumor responses and adverse effects were assessed using the Response Evaluation Criteria in Solid Tumors v1.1 and the Common Terminology Criteria for Adverse Events v3.0, respectively. Results Seventeen patients with a previous cumulative radiation dose of 63-165 Gy were enrolled. All but 2 participants received 2 fractions of BNCT. The median tumor/normal tissue ratio was 3.4 for the first fraction and 2.5 for the second, whereas the median D80 for the first and second fraction was 19.8 and 14.6 Gy-Eq, respectively. After a median follow-up period of 19.7 months (range, 5.2-52 mo), 6 participants exhibited a complete response and 6 exhibited a partial response. Regarding acute toxicity, 5 participants showed grade 3 mucositis and 1 participant showed grade 4 laryngeal edema and carotid hemorrhage. Regarding late toxicity, 2 participants exhibited grade 3 cranial neuropathy. Four of six participants (67%) receiving total D80 > 40 Gy-Eq had a complete response. Two-year overall survival was 47%. Two-year locoregional control was 28%. Conclusions Our results suggested that 2-fraction BNCT with adaptive dose prescription was effective and safe in locally recurrent H&N cancer. Modifications to our protocol may yield more satisfactory results in the future.

Summary Objectives This study investigated the oncogenic miRNA level in the tissue and biofluids in the Nitroquinoline 1-Oxide (4NQO)-induced mouse tongue carcinogenesis model for potential diagnostic or therapeutic application. Materials and methods The histological examination, immunohistochemistry, in situ hybridization, quantitative PCR analysis and bioinformatic algorithms were performed to unravel the signaling activation and miRNA expression in female murine samples. Results The increase of miR-21 and miR-31 staining, and EGFR activation paralleled the severity of 4NQO-induced epithelial pathogenesis in tongue epithelium. A progressive increase of miR-21 , miR-31 and miR-146a in both saliva and plasma samples was also noted. miR-31 was the earliest emerging miRNA in the saliva. The increase of plasma miR-146a , miR-184 and miR-372 was detectable early in the induction, and it was particularly eminent at the most advanced lesion state. The combined analysis of the multiple oncogenic miRNAs in the plasma signified a potent discriminative capacity between normal and pathological states. As the blockage of EGFR or AKT activation drastically reverted the miR-21 , miR-31 and miR-146a expression induced by 4NQO in human oral carcinoma cell lines, the results implicated a mechanistic linkage of the oncogenic miRNAs’ induction through EGFR/AKT activation. Conclusions In this study, we show the dysregulation of oncogenic miRNAs in murine tongue tumorigenesis, which simulates human counterparts. Increased multiple miRNAs in the biofluids may be valuable non-invasive markers in detecting oral carcinogenesis at an early stage. This animal model may also be useful for developing liquid biopsies and prevention strategies against oral carcinoma by abrogating EGFR or oncogenic miRNAs.

Summary Many cell therapies currently being tested are based on mesenchymal stromal cells (MSCs). However, MSCs start to enter the senescent state upon long-term expansion. The role of retinoblastoma (RB) protein in regulating MSC properties is not well studied. Here, we show that RB levels are higher in early-passage MSCs compared with late-passage MSCs. RB knockdown induces premature senescence and reduced differentiation potentials in early-passage MSCs. RB overexpression inhibits senescence and increases differentiation potentials in late-passage MSCs. Expression of DNMT1, but not DNMT3A or DNMT3B, is also higher in early-passage MSCs than in late-passage MSCs. Furthermore, DNMT1 knockdown in early-passage MSCs induces senescence and reduces differentiation potentials, whereas DNMT1 overexpression in late-passage MSCs has the opposite effect. These results demonstrate that RB expressed in early-passage MSCs upregulates DNMT1 expression and inhibits senescence in MSCs. Therefore, genetic modification of RB could be a way to improve the efficiency of MSCs in clinical use., Graphical Abstract, Highlights • RB levels are higher in early-passage MSCs than in late-passage MSCs • RB knockdown induces a premature senescence and reduces differentiation potentials • RB overexpression reverses senescence and increases differentiation potentials • RB upregulates DNMT1 to inhibit senescence and promote differentiation potentials, In this article, Hung, Kao, and colleagues show that retinoblastoma (RB) levels are higher in early-passage mesenchymal stromal cells (MSCs) than in late-passage MSCs, which serves to regulate senescence and differentiation potentials. Expression of DNMT1 is also higher in early-passage MSCs than in late-passage MSCs. This study demonstrates that RB expressed in early-passage MSCs upregulates DNMT1 expression and inhibits senescence in MSCs.

Hypercalcaemia and leucocytosis are common in our patients with progressive oral squamous cell carcinoma (SCC). However, the precise incidence, prognostic value, and correlation with the condition of the tumour remain obscure. A total of 618 patients with oral SCC who were treated primarily between 2007 and 2012 and had serum calcium concentrations and white blood cell count (WCC) measured postoperatively were included in the study. Primary TNM stage, pathological features, and the presence of locoregional recurrence or distant metastasis after comprehensive surgical treatment were recorded. The incidence of hypercalcaemia was 9.1% and that of leucocytosis 7.2%. Hypercalcaemia correlated significantly with size of primary tumour (T status), nodal involvement (N status), TNM stage, perineural invasion, lymphovascular permeation, and recurrence or metastasis of disease. Leucocytosis, however, correlated only with T status, lymphovascular permeation, and recurrence or metastasis. In multivariate analysis of survival, recurrence, metastasis, hypercalcaemia, and leucocytosis were strong independent prognostic factors. Median survival was low if the patient had hypercalcaemia or leucocytosis (179 (range 3–73) days if the patient had distant metastasis, and 43 (range 3–102) days if the patient had locoregional recurrence). The incidence of hypercalcaemia and leucocytosis was high during the course of the disease, and both conditions have an adverse impact on survival from oral SCC. Periodic evaluation of serum calcium concentrations and WCC should be routine during the postoperative period.

MicroRNAs are short non-coding RNAs that regulate gene expression by RNA interference. Oral squamous cell carcinoma (OSCC) is a prevalent malignancy worldwide. miR-146a has been reported to regulate Toll-like receptors and cytokine signaling, which are both crucial for inflammation and oncogenesis. This study identifies that areca nut extract, TNFα and TGFβ up-regulates miR-146a in OSCC cells. The increased expression of miR-146a enhanced the oncogenicity of OSCC cells. In addition, a G to C polymorphism (rs2910164), which is located in the pre-miR-146a and has been associated with functional alterations in miR-146a, was significantly more prevalent among OSCC patients having more advanced nodal involvement. Our analysis also suggested a higher miR-146a expression in OSCC tissues of patients carrying C polymorphism. The present study concluded a higher prevalence of the pre-mir-146a C-variant was associated with OSCC progression in patients with this disease.

Summary Oral squamous cell carcinoma (OSCC) is a common cancer worldwide that is highly lethal due to its recurrence and metastasis. Our candidate-based study aimed to link promoter CpG island hypermethylation to OSCC risk assessment. We examined the promoter hypermethylation status of p16INK4A (p16), glutathione S-transferase pi (GSTP1), O6-methylguanine-DNA methyltransferase (MGMT), death-associated protein kinase 1 (DAPK1), RAS-association domain family 1, isoform A (RASSF1A), and E-cadherin (CDH1) genes in OSCC tumors. Quantitative methylation-specific PCR analysis showed a significant increase in promoter hypermethylation of p16 and CDH1 in OSCC tumors relative to paired non-tumorous tissues. The mean age of patients with hypermethylated p16 was lesser than those without (P = 0.027). Multiple logistic regression predicted patients with hypermethylated p16 have higher risks of lymph node invasion (adjusted OR = 6.21, P = 0.030) in young patients and distant metastasis (adjusted OR = 19.23, P = 0.007) in older patients. Moreover, p16 promoter hypermethylation was significantly associated with shortened disease-free survival (P = 0.034) in older patients. Our results suggested that p16 hypermethylation was associated with early incidence of OSCC, increased lymph node invasion in young patients, and poor prognosis in older patients. Further, p16 hypermethylation may also be implicated in age-related tumor invasion in carcinogenesis.

Osteopontin (OPN) is an extracellular matrix protein in hard tissues. The polymorphism in promoter region of OPN gene correlates to different gene expression and might implicate potential roles in tumor progression and metastasis. Immunohistochemistry (IHC) was utilized to detect the OPN expression in 58 oral squamous cell carcinoma (OSCC) tissues and adjacent normal oral mucosa. The differential OPN expression was further analyzed in relation to clinico-pathological features. Genomic DNA was obtained from isolated leukocytes of blood samples of OSCC patients (n=100), and healthy individuals (n=97) from Taiwan. The OPN gene polymorphism was analyzed by direct sequencing. Our result showed OPN expression was significantly higher in OSCC tissues than in the paired adjacent normal tissues (p

Bmi-1, a member of the Polycomb family of transcriptional repressors, is essential for maintaining the self-renewal abilities of adult stem cells. Bmi-1 has been demonstrated to play a role in tumorigenesis in head and neck squamous cell carcinomas (HNSCCs). A recent study has further suggested that ALDH1 may be considered to be a putative marker for HNSCC-derived cancer stem cells. However, the role that Bmi-1 plays in HNSCC-derived ALDH1-positive cells (HNSCC-ALDH1(+)) has yet to be determined. In this study, we demonstrated that HNSCC-ALDH1(+) cells possess tumor initiating properties, are capable of self-renewal, and express higher levels of Bmi-1 as compared to HNSCC-ALDH1(-) cells. To further explore the functional role of Bmi-1 in HNSCC-ALDH1(+) cells, we used a lentiviral vector expressing shRNA to knock down Bmi-1 expression (sh-Bmi-1) in HNSCC-ALDH1(+) cells. Silencing of Bmi-1 significantly enhanced the sensitivity of HNSCC-ALDH1(+) cells to chemoradiation and increased the degree of chemoradiation-mediated apoptosis that occurred. Importantly, knockdown of Bmi-1 increased the effectiveness of radiotherapy and led to the inhibition of tumor growth in nude mice transplanted with HNSCC-ALDH1(+) cells. Kaplan-Meier survival analysis indicated that the mean survival rate of HNSCC-ALDH1(+) tumor-bearing immunocompromised mice treated with radiotherapy was significantly improved by treatment with sh-Bmi-1 as well. In summary, these results suggest that Bmi-1 is a potential target for increasing the sensitivity of HNSCC cancer stem cells to chemoradiotherapy.

Background: This study was undertaken to investigate the facial skeletal features associated with chin deviation. Methods: Twenty-five patients (14 males and 11 females) diagnosed with chin deviations of more than 2 mm were recruited. Fifteen skeletal landmarks, including median and lateral points, were located on posteroanterior cephalograms. The CG–ANS (crista-galli of the ethmoid–anterior nasal spine) line and the perpendicular line through the CG were used as references. The differences between the distances from paired lateral points to reference lines were examined with intraclass correlation coefficients to analyze the symmetry of facial skeletal tissue. The factors associated with the amount or direction of chin deviation were analyzed by multiple regression analysis or by logistic regression analysis. Results: Seventeen subjects (68%) showed chin deviation to the left side and 8 subjects (32%) to the right side. Sixtyeight percent of subjects presented with Angle Class III malocclusion. Horizontal distances of all paired lateral points to the y-axis, in mandibular body length and effective length, showed a low grade of symmetry. Only vertical distances of paired zygomaticofrontal sutures and zygonion points to the x-axis were asymmetric. However, there were no significant asymmetries of the gonial angle, ramus height, and vertical distances from other paired lateral points to the x-axis. The amount of chin deviation was associated with the absolute differences of the left and right antegonion to the y-axis and zygomaticofrontal suture to the x-axis. The direction of chin deviation was significantly associated with the difference in the effective length of bilateral mandibular halves. Conclusion: Facial skeletal asymmetry exists in patients with chin deviation. This should be considered when planning treatment for both the nonsurgical and surgico-orthodontic cases with chin deviation. [J Chin Med Assoc 2010;73(1):29–34]

HER-2 proto-oncogene is important for oral carcinogenesis. HER-2 codon 655 polymorphism, either isoleucine (Ile: ATC) or valine (Val: GTC), was associated with the risk of breast carcinoma. This study investigated the clinicopathological implications of this polymorphism in oral carcinoma. We found that 79% of oral carcinoma patients had A/A (Ile/Ile) genotype and 21% had A/G (Ile/Val) genotype, with a G (Val) allelic frequency of 0.10. Univariate analysis indicated a significantly higher Val allelic frequency in cases having nodal metastasis or tumor recurrence; and Val allele was associated with poorer recurrence-free survival of patients. Multivariate analysis after adjusting confounding factors by logistic regression analysis indicated that patients carrying Val allele had a 8.79- and 4.25-fold higher risk for nodal metastasis and recurrence, respectively. Using Cox proportional hazard model, the risk of tumor recurrence was 3.35-fold higher in patients carrying Val allele. This is the first report demonstrating that the Val allele of HER-2 codon 655 could be an independent predictor for oral carcinoma progression.

Oral cancer is a fatal disease, accounting for the fourth highest incidence of malignancy in males and the seventh in females in Taiwan. The relatively high prevalence of oral cancer in Taiwan is mainly because there is a high-risk group of 2.5 million people with the habit of smoking and betel nut chewing. Unfortunately, 50% of new cases in our medical center who present with TNM stage III or IV lesions have a shorter than 5-year survival after treatment. This highlights the need for: (1) early treatment of fresh oral cancer cases; (2) screening of the high-risk population to detect new lesions; (3) careful follow-up of cases after treatment; and (4) detection of occult early neck nodal adenopathy in surgical cases. It is generally accepted that prevention and screening of oral cancer are equally important to treatment due to its location. In this review article, we describe the nature of oral cancer and highlight the various conventional and novel methods of screening for this disease and ongoing important related research. Related literature is reviewed and future work that needs to be done is detailed.

During the last decade, the effectiveness of implant therapy has greatly improved, and the demands of dental esthetics in implant dentistry have become an important issue. The traditional two-stage implant protocol with delayed restoration has a treatment duration of 1–2 years, in which patients had to wear a removable appliance and experienced significant discomfort during the recovery period. Nowadays, immediate implant placement into an extraction site followed by immediate restoration of a dental implant can shorten the dental rehabilitation time and preserve patients' esthetic appearance at all stages of treatment. However, these treatment protocols always pose a great challenge to clinicians, especially when treating patients with preexisting soft and hard tissue deficiencies. The aim of this report is to present various treatment modalities to provide immediate tissue reconstruction and implant restoration following tooth extraction. With appropriate patient selection and careful clinical planning, these treatment strategies can lessen the number of surgeries required, condense treatment times, reduce discomfort to the patient, and accelerate the restoration process.

A 50-year-old man with severe malocclusion requested comprehensive oral rehabilitation. He presented with retrognathic mandible, anterior deep bite and a gummy smile in the premaxilla, and tenting occlusal plane with severe buccal crossbite of the left maxillary posterior teeth. Inappropriate fixed prostheses spanned the maxilla and the mandible with a class II jaw relationship. A detailed analysis indicated the need for orthodontic treatment, orthognathic surgery, bone graft at the deficient alveolar ridge for implant surgery and a revision of all prostheses. Over a 2-year-period of management, the patient received anterior osteotomy for intrusion of lower anterior teeth, bilateral sagittal splitting osteotomy for mandible advancement and posterior osteotomy for inward upward repositioning of posterior teeth of the left maxilla to correct major jaw deformities. The deficient alveolar ridge in the premaxilla was augmented by autogenous bone graft harvested during the orthognathic surgery. He sequentially had mini-plate and dental implant as anchorage assisting teeth alignment in the mandible. Two 3-fixture-supported implant prostheses were delivered in the premaxilla and the mandible. The improvement in cosmesis, stability and function through treatment and a 2-year clinical follow-up were considered satisfactory.

The overall prognosis for tongue cancer patients in Taiwan is unpredictable, even when patients are treated following the guidelines according to TNM stages. In order to determine the optimal treatment modality for tongue cancer in Taiwan the authors aimed to correlate histopathological parameters with neck nodal metastasis. A retrospective analysis of 94 patients with different stages of tongue cancer treated in the Taipei Veterans General Hospital was performed. All 94 patients were clinically diagnosed with stage I-IV tongue cancer before surgery and received primary tumor-wide excision and neck dissection. There were 42 (45%) patients with nodal metastasis. Univariate analysis revealed that cases of tongue cancer with moderate or poor differentiation, an invasion depth more than 3 mm and positive perineural invasion or lymphovascular permeation at the time of presentation may be subject to a higher incidence of neck nodal metastasis. An elective neck dissection or neck treatment should be considered if these histopathological risk factors are present. Cases of tongue cancer with these risk factors also warrant close follow-up after surgery.

Background and Purpose The p 53 tumor suppression pathway is important in effects associated with radiotherapy. The mouse double minute 2 (MDM2) plays a pivotal role in this pathway by down regulating p 53 . A functional T-to-G polymorphism at nucleotide 309 in MDM2 promoter intron 1 (SNP309) has been identified which influenced transcription activity. A G-to-C SNP at p 53 codon 72 results in an Arg/Pro polymorphism, which is associated with apoptosis induction potential and p 53 mutation status. Materials and methods We sequenced both MDM2 SNP309 and p 53 codon 72 SNP in patients with oral squamous cell carcinoma (OSCC, n = 189 ), oral submucosal fibrosis (OSF, n = 70 ), and 116 controls. Results Neither MDM2 SNP309 nor p 53 codon 72 SNP was associated with susceptibility to or the age at onset of OSCC or OSF. p 53 codon 72 SNP Arg/Arg polymorphism was associated with the progression of OSCC, and the overall (OS) and disease-free survival (DFS) of irradiated patients. The MDM2 SNP309 G/G polymorphism was associated with poor OS in advanced OSCC, and the OS and DSF of irradiated patients. The combination of MDM2 SNP309 G/G and p 53 codon 72 Arg/Arg polymorphism is associated with the worst OS and DFS. Conclusions Advanced OSCC has high mortality and recurrence. We identified that both MDM2 SNP309 and p 53 codon 72 SNP could be useful factors for evaluating the outcome of advanced OSCC treated with adjuvant radiation.

Radiation-induced sarcoma (RIS) or postirradiation sarcoma has been reported rarely as a long-term complication of radiation therapy (RT). We report 4 cases of oral sarcomas or sarcomatoid tumors with a rather short latency period after radiotherapy of the prior OSCC. Histopathological evaluation and immunohistochemical study were performed using a panel of markers including vimentin, cytokeratin, S-100, desmin, myoglobin, HHF-35, p53, and p16. All reported cases were positive for vimentin and negative for cytokeratin. Two cases were positive for myoglobin, desmin, or HHF-35, and were probably myogenic origin. One case was possibly a fibrosarcoma and the subclassification of the other one was not specified. Diverse expression of p53 and p16 was further observed in these 4 cases. Report of the complicated clinical processes and the analysis of genetic markers of these cases provide useful clinical and pathogenetic insights of mesenchymal malignancies associated with a status post OSCC radiation.

Purpose The present study was undertaken to retrospectively evaluate the status of implants in patients subjected to a maxillary sinus lift and immediate implant placement without bone grafting. Patients and Methods Seventy-five implants were placed in 47 patients from 2000 to 2006. Lateral approach for the trap-door, open-window method for sinus lifting without placement of either autogenous bone grafts or allogeneic bone substitute was carried out. A 5-mm of the bone level was required in the alveolar ridge for all. All implants were placed synchronously with sinus lifting procedure. Patients underwent strict oral hygiene instruction, periodontal charting, presurgical/postsurgical panoramic radiographs, and postsurgical computed tomographic scan during the follow-up. The implant survival was defined when the prosthesis had been delivered and followed for 2 years without infection, pain, or more than 2-mm peri-implant bone loss. Results Thirty-three patients (23 males, 10 females) having an average age of 55 years old, with a total of 47 fixtures were followed for more than 2 years after prosthesis delivery. No patients developed sinusitis or other complications leading to loss of an implant subsequent to performance of the sinus lifting-combined immediate implant surgery. The 2-year survival of fixture was 100%. Increases in lifted sinus bone height ranged from 3 mm to 9 mm with an average of 4.5 mm. The peri-implant health was judged to be good with a peri-implant sulcus depth of 2.7 ± 0.5 mm at 2-year follow-up. Conclusions A good survival rate was observed in the immediate implant placement synchronously with the lateral approach for maxillary sinus lift without bone grafting.

A 32-year-old male presented with an exophytic, pink, raw-surfaced mass over the gingiva, 4 × 4 × 3 cm in size and extending from the right upper central incisor to the first molar. A biopsy revealed a rarely occurring spindle cell carcinoma of the oral cavity. As past medical history and pathological reports bore little relation to the present illness, the patient received radical surgery and postoperative radiotherapy and chemotherapy. Even so, the local aggressiveness and early metastatic behaviour of the tumour eventually proved fatal. Spindle cell carcinoma is an uncommon tumour of uncertain histogenesis that typically arises as a biphasic polypoid tumour. Dual expression of cytokeratin and vimentin make its differential diagnosis difficult. We describe this rarely occurring tumour, with early bilateral neck, bone and lung metastases, that warrants clinical attention for correct diagnosis at an early stage.

Areca (betel) is an important etiological factor linked to the high prevalence of oral carcinoma and other oral diseases in South Asians. Involucrin is a key component of the cornified envelop and a differentiation marker of keratinocyte. In this study, we found that 5 microg/ml non-toxic areca nut extract (ANE) treatment resulted in the 0.5-fold down-regulation of involucrin and disruption in involucrin distribution in normal human oral keratinocyte (NHOK). Progressive down-regulation of involucrin during oral carcinogenesis was noted. Activation of AKT by 1.7-fold and up-regulation of COX-2 by 2-fold were elicited following ANE treatment in NHOK. Treatment with PI3K/AKT blockers reverted the down-regulation of involucrin. ANE also down-regulated involucrin by 0.6-fold and disturbed both cornified envelope and cell aggregation in calcium-induced differentiated NHOK. However, such phenomena seemed to be independent from the ANE-associated COX-2 activation. The ANE-associated down-regulation of involucrin through AKT pathway could underlie the areca-associated epithelial pathogenesis.

Objective: To investigate the use of positron emission tomography for the detection of cervical metastases of oral squamous cell carcinoma. Materials and Methods: Twenty four patients with histologically confirmed oral squamous cell carcinoma, without previous surgery, radiation therapy, or chemotherapy, and with pretreatment computed tomography and positron emission tomography scans, were included. In this retrospective chart review, data were collected for computed tomography and positron emission tomography findings, treatment, and outcomes. The findings for computed tomography, positron emission tomography, and histopathology were analysed by paired Fisher's exact t test. Results: A statistically significant correlation was noted between computed tomography and positron emission tomography findings (p = 0.033) as judged by the histopathology results of 8 neck dissections. No correlation was found between computed tomography findings or positron emission tomography and histopathology. Among the 14 patients with positive computed tomography and positron emission tomography scans, 9 were ultimately documented to have cervical metastases. Among the 6 patients with negative computed tomography and positive positron emission tomography, 5 had neck lymph node metastases (p = 0.048) during followup, while patients with negative positron emission tomography did not show neck metastases. Conclusion: In comparison with conventional computed tomography, positron emission tomography provided additional information for the detection of cervical lymph node metastases of oral squamous cell carcinoma. The importance of positron emission tomography for the early detection of neck lymph node metastases is emphasised.

Objective: To propose a sequential treatment approach for implant rehabilitation of a traumatised and deficient maxillary or mandibular alveolar ridge. Patients and Methods: Patients with severely deficient alveolar ridge and loss of teeth due to injury underwent sequential reconstructive procedures at the maxillary or mandibular edentulous areas with autogenous symphyseal bone or allogeneic bone graft with guided bone regeneration; vestibuloplasty with or without keratinised palatal mucosal graft to rebuild the vestibule; and implant rehabilitation. Postoperative followup consisted of clinical and radiographic examinations. Results: Thirty six implant fixtures were placed in the maxilla or mandible in 12 patients. The average follow-up period after treatment was 4 years. Before surgery, all patients had severely deficient ridges with a compromised shallow vestibule. Satisfactory results were observed in regard to the long-term stability of the rehabilitation result, contour of the reconstructed ridge, morphology of the vestibule, health of the periimplant tissue, and functionality of the implant-retained prostheses. Conclusion: The proposed sequential reconstructive treatment approach for both hard and soft tissues offers a reliable method of implant rehabilitation after traumatic injury.

Purpose This study was an analysis of the soft and hard tissue changes of the facial profile after bilateral sagittal splitting osteotomy for mandibular setback of Taiwanese patients. Patients and methods We collected pre- and postsurgical lateral cephalographs of 64 patients (28 males, 36 females) with skeletal Class III malocclusion who received combined orthodontic-surgical treatment with bilateral sagittal splitting osteotomy mandibular setback at Taipei Veterans General Hospital between 1994 and 2000. Nineteen cephalometric parameters of (14 linear, 4 angular, and the BS index) soft and hard tissues were measured at 1 week before treatment, and 2 months and 1 year after surgery, and analyzed by paired t test. Results Mean patient age was 20.0 ± 1.6 years. The patients underwent an average of 7 mm mandibular setback at the osseous pogonion (Pog). Average setbacks at Pog and soft tissue pogonion (pog) were 5.54 mm and 4.85 mm, respectively, at 1 year after surgery. The setback ratio of Pog/pog was 1:0.88. The hard tissue relapse at Pog was 21% at 1 year after surgery. Improvement in prognathic profile was demonstrated by significant changes in the positions of Pog and pog, ANB angle, the distance from lower lip to esthetic line (E-L lip), and the BS index after surgery. However, compared with parameters obtained from a normal Taiwanese population, the cephalometric data of Pog, pog, and BS index still indicated mild prognathism. Conclusion Although mandibular prognathism could be grossly improved by bilateral sagittal splitting osteotomy mandibular setback, a significant amount of relapse occurred within 1 year after surgery. The extent of the postoperatively preserved features showing mandibular prognathism should be a concern for both patients and physicians.

A peripheral T-cell lymphoma in a 58-year-old man presenting in the right maxillary gingiva with invasion of bone is reported. Treatment was chemotherapy with cyclophosphamide, vincristine, and prednisolone, followed by right maxilla sequestrectomy due to necrosis of soft tissue and bone. Pathological examination of the tumour tissue showed a T-cell lymphoma with characteristic large pleomorphic lymphoid cell infiltration with angio-invasion. The neoplastic lymphoid cells were positive for leukocyte common antigen, CD3, and Epstein-Barr virus stain and negative for L-26, CD2, CD5, and CD56.

Objective: Oral squamous cell carcinoma is the fifth most common malignancy among Taiwanese men. Telomerase reactivation is thought to be related to unregulated growth of tumour cells. Telomerase activity in oral squamous cell carcinoma cells, but not in normal somatic cells, suggest that it is a potential target for therapy. In this study, we used antisense oligonucleotide, which acts against human telomerase RNA and telomerase-associated protein 1, to investigate the connection between telomerase inhibition and cancer therapy. Materials and Methods: An in vivo tumour model was established with athymic nude mice and oral squamous cell carcinoma cell line-KB. Oligonucleotides with anti-human telomerase RNA and anti-telomerase-associated protein 1 were injected intratumourally twice a week for 2 weeks. The antiproliferative effect was measured by changes in tumour volume, and a telomeric repeat amplification protocol was used to determine telomerase activity. Results: Xenografted oral squamous cell carcinoma cells were established 3 weeks after inoculation. There were no statistically significant differences between the treatment and control groups in tumour volume change or telomerase activity. Conclusions: In this in vivo study, we successfully established an oral cancer cell line in an animal model. A high degree of telomerase activity was noted among the oral cancer cells. Antisense oligonucleotide use had a mild suppressive effect on tumour growth and telomerase activity. However, we could not define its therapeutic significance. Further fine-tuning of administration routes, types of vectors for antisense oligomers, targets for antisense oligomers, and different oral cancer cell lines may improve the results of anti-telomerase therapy.

We present a rare case of oral metastatic epithelioid sarcoma rapidly growing over the mandibular gingivae; the primary lesion occurred on the wrist and was treated 18 months earlier by surgery and radiotherapy. The oral metastatic lesion was resected and controlled by chemotherapy. This case has been followed for 2 years with good control of the resected oral metastatic lesion. Histologically, round to oval-shaped tumour cells with abundant eosinophylic globular cytoplasm and eccentrically localized nuclei, lack of epithelial features by electron microscopic study, and the immunohistochemical and cytologic features of tumour cells led into the diagnosis of epithelioid sarcoma. To our knowledge, no reports have been published of its occurrence in the oral cavity

Accumulation of mitochondrial DNA (mtDNA) mutations in human tissues has been associated with intrinsic aging and environmental insult. Recently, mtDNA mutations have been detected in various tumors, including head and neck tumors. However, the factors affecting the occurrence and accumulation of mtDNA deletions in tumor tissues are poorly understood. In Taiwan, betel quid chewing is a major risk factor for oral cancer. Using polymerase chain reaction (PCR) techniques, we examined large-scale deletions of mtDNA in 53 pairs of tumor and non-tumor oral tissues from the patients with or without betel quid chewing history. The results revealed that irrespective of the history of betel quid chewing, the incidences of the 4977bp deletion and other deletions of mtDNA were lower in the tumor portion as compared with the non-tumor portion. The average proportions of the 4977bp deleted mtDNA in the tumor tissues of the betel quid chewers and non-betel quid chewers were 13- and 5-fold, respectively, lower than those in the corresponding non-tumor tissues. Moreover, the average proportion of 4977bp deleted mtDNA was significantly higher (P

We report a case of aspergillosis in the right temporomandibular joint (TMJ) with a history of parotid carcinoma and post-irradiation otitis. Previous treatment attempts with surgery and antibiotics were unsuccessful. Radical debridement of the glenoid fossae, supplemented with amphotericin B and adjunct hyperbaric oxygen (HBO) therapy, was provided to resolve the symptoms. This case report highlights the need to be aware of the possibility of invasive mycosis in immunocompromised patients.

MicroRNAs (miRNAs) play important roles in modulating the neoplastic process of cancers including head and neck squamous cell carcinoma (HNSCC). Purpose A genetic polymorphism (rs2292832, C > T) has been recently identified in the precursor of miR-149; nevertheless its clinicopathological implications remain obscure. Material and methods 273 HNSCC patients and 122 healthy controls were enrolled for genotyping analysis and HNSCC cell lines including SAS, OECM-1, FaDu were chosen for phenotypic assay regarding to miR-149 expression. Results We showed that miR-149 is down-regulated in HNSCC compared to normal mucosa and this is associated with a poorer patient survival. In addition, HNSCC patients with the T/T genotype have more advanced tumors and a worse prognosis. Multivariate analysis indicated that patients carried the T/T genotype have a 2.81-fold (95% CI: 1.58–4.97) increased risk of nodal metastasis and 1.66-fold (95% CI: 1.05–2.60) increased risk of mortality compared to other groups. T/T genotype also predicted the worse prognosis of buccal mucosa carcinoma subset of HNSCC. In vitro analysis indicated that exogenous miR-149 expression reduces the migration of HNSCC cells. Moreover, HNSCC cell subclones carrying the pri-mir-149 sequence containing the T variant show a low processing efficacy when converting the pre-mir-149 to mature miR-149. Conclusions These findings suggest that miR-149 suppresses tumor cell mobility, and that the pre-mir-149 polymorphism may affect the processing of miR-149, resulting in a change in the abundance of the mature form miRNA, which, in turn, modulates tumor progression and patient survival.

Mammalian target of rapamycin (mTOR) is an important regulator of protein translation, biosynthesis, cell growth and cell proliferation, is over-activated in various human malignancies, but very few studies have yet to explore the mTOR activity in oral squamous cell carcinoma (OSCC), which is the 7th leading death of malignancy in Taiwan. We collect tissue samples of 58 OSCC patients from Taipei veteran general hospital during along with their clinical parameters. Immunohistochemical (IHC) staining was performed on the tissues for investigating active mTOR (p-mTOR) expression level with the use of tissue microarray (TMA) technique. The results revealed p-mTOR expression level in OSCC tissues are significantly higher than in normal oral mucosal tissues ( p p = 0.0391) and higher tumor recurrence after adjuvant cisplantin treatment ( p = 0.0159). Although positive group shows a relatively rapid descent on survival curves, no significant difference between positive and negative group in over-all survival rate ( p = 0.1064), cancer specific survival rate ( p = 0.0914) and disease free survival rate ( p = 0.0509). p-mTOR expression level in OSCC correlates to tumor recurrence, possible poorer survival rate and may even associate with cisplantin resistance in our study. A scale-up study in the future may further elucidate the role of mTOR in OSCC.