Ya-Wei Chen

Chromosome Instability Modulated by BMI1–AURKA Signaling Drives Progression in Head and Neck Cancer

Chromosomal instability (CIN) is widely considered a hallmark of cancer, but its precise roles in cancer stem cells (CSC) and malignant progression remain uncertain. BMI1 is a member of the Polycomb group of chromatin-modifier proteins that is essential for stem cell self-renewal. In human cancers, BMI1 overexpression drives stem-like properties associated with induction of epithelial-mesenchymal transition (EMT) that promotes invasion, metastasis, and poor prognosis. Here, we report that BMI1 mediates its diverse effects through upregulation of the mitotic kinase Aurora A, which is encoded by the AURKA gene. Two mechanisms were found to be responsible for BMI1-induced AURKA expression. First, BMI1 activated the Akt pathway, thereby upregulating AURKA expression through activation of the β-catenin/TCF4 transcription factor complex. Second, BMI1 repressed miRNA let-7i through a Polycomb complex-dependent mechanism, thereby relieving AURKA expression from let-7i suppression. AURKA upregulation by BMI1 exerts several effects, including centrosomal amplification and aneuploidy, antiapoptosis, and cell-cycle progression through p53 degradation and EMT through stabilization of Snail. Inhibiting Aurora A kinase activity attenuated BMI1-induced tumor growth in vivo. In clinical specimens of head and neck cancer, we found that coamplification of BMI1 and AURKA correlated with poorer prognosis. Together, our results link CSCs, EMT, and CIN through the BMI1-AURKA axis and suggest therapeutic use from inhibiting Aurora A in head and neck cancers, which overexpress BMI1.

Detection and Screening of Oral Cancer and Pre-cancerous Lesions

&NA; 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.

Histopathological factors affecting nodal metastasis in tongue cancer: analysis of 94 patients in Taiwan

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 3mm 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.

Application of In Vivo Stain of Methylene Blue as a Diagnostic Aid in the Early Detection and Screening of Oral Squamous Cell Carcinoma and Precancer Lesions

Background: Early detection of oral malignant or precancerous lesion by screening individuals with high‐risk factors may identify candidates who should receive treatment to prevent cancer progression and reduce patient mortality. Among the diagnostic tools, in vivo staining is advocated as a simple, inexpensive, and fairly sensitive method. Methods: The present study involved the examination of fifty‐eight patients suspected of having oral malignant or precancerous lesions by methylene blue staining. The results of methylene blue uptake were compared with a simultaneous biopsy of these lesions. The pathologically confirmed precancers and cancers were the positive targets of this screening, while benign epithelial lesions were sorted as negative subjects of screening. Results: The results revealed sensitivity of 90%, specificity of 69%, positive predictive value of 74%, and negative predictive value of 87%. Conclusion: We consider that methylene blue staining is a useful diagnostic adjunct in a large, community‐based oral cancer screening program for high‐risk individuals.

Histone modification patterns correlate with patient outcome in oral squamous cell carcinoma

Patterns of global histone modifications have been suggested to be predictors of clinical outcome in many cancers. However, the role of global histone modification patterns in oral squamous cell carcinoma (OSCC) is unclear.

Botulinum toxin therapy for temporomandibular joint disorders: a systematic review of randomized controlled trials

The objective of this study was to undertake a systematic review to assess the efficacy of botulinum toxin therapy (BTX) for temporomandibular joint disorders (TMDs). A comprehensive search of major databases through PubMed, EMBASE, and Cochrane CENTRAL was conducted to locate all relevant articles published from inception to October 2014. Eligible studies were selected based on inclusion criteria and included English language, peer-reviewed publications of randomized controlled trials comparing BTX versus any alternative intervention or placebo. Quality assessment and data extraction were done according to the Cochrane risk of bias tool and recommendations. The entire systematic search and selection process was done independently by two reviewers. Five relevant study trials were identified, involving 117 participants. Two trials revealed a significant between-group difference in myofascial pain reduction, another trial that compared BTX with fascial manipulation showed equal efficacy of pain relief on TMDs, while the remaining two trials showed no significant difference between the BTX and placebo groups. Because of considerable variations in study methods and evaluation of results, a meta-analysis could not be performed. Based on this review, no consensus could be reached on the therapeutic benefits of BTX on TMDs. A more rigorous design of trials should be carried out in future studies.

Analysis of p16INK4A expression of oral squamous cell carcinomas in Taiwan: Prognostic correlation without relevance to betel quid consumption†

In this study, we examined the role of p16INK4A, a surrogate biomarker of HPV‐related head and neck cancers with better prognosis, in an endemic area of betel quid (BQ)‐related oral squamous cell carcinoma (OSCC).

Oral health status of children with special health care needs receiving dental treatment under general anesthesia at the dental clinic of Taipei Veterans General Hospital in Taiwan

Background: Oral health is crucial to individual growth and development. However, oral health care is often overlooked in children with special health care needs (CSHCN). We investigated current oral health status and unmet dental needs of CSHCN in Taiwan. Methods: We performed a retrospective study of consecutive CSHCN cases receiving first‐time comprehensive dental treatment under general anesthesia at Taipei Veterans General hospital from 2001 to 2010. We retrieved clinical data including age, sex, types, and severity of disability, caries experience index [decayed, extracted, and filled teeth (deft) index for primary dentition/decayed, missing, and filled teeth (DMFT) index for permanent dentition], malocclusion, and treatment modalities from medical charts for analysis. The correlation between different groups of CSHCN regarding the deft/DMFT indices and treatment modalities was analyzed statistically. Results: Our study included 96 children, ranging in age from 2.4 years to 14.3 years (mean age 6.8 ± 3.3 years). The deft/DMFT index was significantly higher in the younger age group (2–6 years; 13.8 ± 4.3) compared with the older group (> 6 years; 10.5 ± 5.3; p < 0.001). The mean number of total treated teeth was 14.2 ± 3.8, and no differences existed among disability groups (p = 0.528) and age groups (p = 0.992). For the treatment modality, the number of pulp therapies with crown restoration was higher in the younger age group than in the older group. At the time of the study, 53 CSHCN had reached their full permanent dentition. We observed significantly more malocclusion of full permanent dentition in the older age group (91%) than in the younger group (35%; p < 0.001). Conclusion: Unmet dental needs and caries experience indices remain high in CSHCN, regardless of the types and severity of disability. However, the younger the age at which CSHCN received their first dental treatment, the more effective the dental rehabilitation was. Parental education regarding early dental intervention and a preventive approach for enhanced oral care is mandatory.

Prognostic value of hypercalcaemia and leucocytosis in resected oral squamous cell carcinoma.

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.

Predictors and impact of microsurgical complications in patients with locally advanced oral squamous cell carcinoma

Microvascular free flap transfer for post‐oncologic reconstructive surgery in oral cancer is considered to be a challenge due to the complexity of the anatomy and function of the region. We sought to identify possible factors associated with microsurgical complications and to assess the impact of these complications in relation to patient survival. Following the inclusion and exclusion protocol, 142 patients with stage III and IV oral squamous cell carcinoma (OSCC) who underwent immediate free flap reconstruction after tumor ablation were included in the study. Clinical and surgical procedural‐related factors were retrieved from a database and analyzed retrospectively; survival data were evaluated using the Kaplan–Meier method. Major complications that required re‐anastomosis of the flap vessels occurred in 23 patients (16.2%); total necrosis of the flaps, regardless of salvage treatment, occurred in seven cases, with 95.1% of full flap survival. The American Society of Anesthesiologists classification, types of neck dissection, and number of flaps were regarded as strong predictors for surgical complications. Patients with these complications appeared to have a shortened survival (5‐year cancer‐specific survival of approximately 60%, both in stage III and IV OSCC). However, the impact of surgical complications on survival was significant only in stage III OSCC (P = 0.037). Strategies to minimize surgical complications should be used to ensure better prognoses for these patients.