Clinical study of keratocystic odontogenic tumors

The odontogenic keratocyst (OKC) was originally classified as a developmental cyst, and OKCs were histologically divided into orthokeratotic (O-OKCs) and parakeratotic (P-OKCs) types. Clinical features differ between O-OKCs and P-OKCs with P-OKCs having a tendency to recur after surgical treatment. According to the revised histopathological classification of odontogenic tumors by the World Health Organization (2005) , the term keratocystic odontogenic tumor (KCOT) has been adopted to describe P-OKCs. In this retrospective study, we examined 186 KCOTs treated at the Maxillofacial Surgery Department of the Tokyo Medical and Dental University Hospital from 1981 through 2005. The patients ranged in age from 7 to 85 years (mean, 32.7) and consisted of 93 males and 93 females. The most frequently treated areas were the mandibular molar region and ramus. The majority of KCOTs in the maxillary region were treated by enucleation and primary closure. The majority of KCOTs in the mandibular region were enucleated, and the wound was left open. Marginal resection was performed in the 4 patients with large lesions arising in the mandible. In patients who were followed for more than a year, recurrences were observed in 19 of 120 lesions (15.8%) . The recurrences were found at the margins of the primary lesion in contact with the roots of the teeth or at the upper margins of the mandibular ramus. Clinicians should consider aggressive treatment for KCOTs because the recurrence rate of P-OKCs is higher than that of other cyst types such as O-OKCs, dentigerous cysts, primordial cysts that were non-keratinized, and slightly keratinized stratified squamous epithelium. Although more aggressive treatment is needed for KCOTs as compared to other cystic lesions, it is difficult to make a precise diagnosis preoperatively on the basis of clinical features and X-ray imaging. Therefore, preoperative biopsy is necessary for selecting the appropriate treatment for patients with cystic lesions.

Complications and Outcome of Free Flap Transfers for Oral and Maxillofacial Reconstruction / Oral Science International

Microvascular free flap transfers have become a preferred reconstructive technique; however, rare complications may still prove devastating. This study reviewed 213 consecutive free-tissue transfers in order to assess the incidence and causes of complications in patients undergoing microvascular free flap reconstruction in the oral and maxillofacial region. In most cases, reconstruction was undertaken after resection of a malignant tumor. The flap donor sites were the radial forearm (n=111), rectus abdominis (n=88), scapula (n=13), and latissimus dorsi (n=1). The superior thyroid artery and the external jugular vein were commonly used as recipient vessels for anastomosis. The overall flap success rate was 99%. There were 7 cases of postoperative vascular thrombosis (6 venous and 1 arterial), constituting 3.3% of the entire series. Five flaps were salvaged, representing a 71.4% successful salvage rate in cases of vascular complications. Most of the successful salvage attempts were made within 24 hours of the end of the initial operation, and the successful salvage rate for re-exploration was 100%. Finally, the total flap loss rate was 0.9% and the partial flap loss rate was 2.3%. We conclude that early re-exploration should be the first choice for management of vascular compromised flaps. Complications at the donor site occurred in 17 cases (8.0%), the most common complication of which was partial skin graft loss after harvesting a radial forearm flap (n=10; 9.0%). Recipient and donor site morbidity was limited and considered acceptable.

Simultaneous Assessment of Cyclin D1 and Epidermal Growth Factor Receptor Gene Copy Number for Prognostic Factor in Oral Squamous Cell Carcinomas / Oral Science International

Cyclin D1 gene (<i>CCND1</i>) numerical aberrations are independent prognostic indicators of head and neck squamous cell carcinomas (HNSCCs). High epidermal growth factor receptor gene (<i>EGFR</i>) copy number is associated with poor prognosis in lung cancer, but such findings are controversial in oral SCCs (OSCCs). We analyzed copy number status in <i>CCND1</i> and <i>EGFR</i> in OSCC patients and its association with clinical outcome.<i>EGFR</i> and <i>CCND1</i> statuses were analyzed in 85 OSCC patients by fluorescence <i>in situ</i> hybridization (FISH) of specimens obtained by fine-needle aspiration biopsy.<i>CCND1</i> numerical aberration was found in 35 of 85 tumors (41%), and aberrant <i>EGFR</i> copy number was observed in 36 (42%). Gene amplification (GA) was dominant among <i>CCND1</i> copy number changes (14/35:40%). Balanced trisomy (BT) was the most frequently observed <i>EGFR</i> aberration (17/36:47%). In a multivariate Cox's proportional hazards analysis, <i>CCND1</i> GA was correlated with disease-free survival (<i>P</i><0.001), whereas <i>EGFR</i> BT was significantly correlated with overall survival (<i>P</i>=0.001). Patients with a combination of <i>CCND1</i> GA and/or <i>EGFR</i> BT had significantly poorer clinical outcome.<i>CCND1</i> and <i>EGFR</i> copy number changes were frequent in OSCC and had differing aberration patterns. <i>CCND1</i> GA and <i>EGFR</i> BT statuses by dual-color FISH were the predominant predictors of clinical outcome. Further investigation is needed to determine the implications for EGFR inhibitor therapy in OSCC.

Multilineage Cells from Apical Pulp of Human Tooth with Immature Apex / Oral Science International

The human tooth with immature apex is a developing organ available for investigation. In this tooth, especially in the apical pulp, the proliferation and differentiation of various cells are activated to make a complete tooth. We investigated the notion that unique cells are included in the apical pulp of human tooth with immature apex. Human impacted third molars with immature apex freshly extracted for orthodontic reasons or treatment were obtained. Histological analyses revealed that BrdU-incorporating cells and cells positive for the mesenchymal stem cell markers SH2 and SH3 were located in the same region. The cells from the apical pulp of a human tooth with immature apex, designated here as apical pulp-derived cells (APDCs), can be cultured easily <i>in vitro</i> under ordinary serum-supplemented culture condition. The expression of surface markers of expanded APDCs is similar to that of bone marrow mesenchymal stem cells, except for CD49d (α4-integrin). APDCs differentiated into mineralized cells, adipocytes, chondroblasts and neural cells <i>in vitro</i>. APDCs have a high capacity for proliferation and multilineage potential <i>in vitro</i>. Our results indicate that human tooth with immature apex is a precious tissue source for the research of human adult stem cells and for the advancement of dental and regenerative medicine.

Oral Leukoplakia Related to Malignant Transformation / Oral Science International

Oral leukoplakia and its malignant transformation are reviewed in this article. Oral leukoplakia is defined as a predominantly white lesion of the oral mucosa that can not be characterized as any other definable lesion; however, the lesion must be confirmed histopathologically by biopsy in order to discuss malignant transformation of oral leukoplakia. Malignant transformation rates of oral leukoplakia range from 0.13 to 17.5%, while the rates of five-year cumulative malignant transformation range from 1.2 to 14.5%. Some reports found a high incidence of malignant transformation in older patients. Chewing tobacco and smoking are distinct risk factors particularly among males in certain countries; however, other countries have noted that females or non-smokers may be at risk of malignant transformation. HPV has been detected in oral dysplasia lesions and cancer in non-smokers. Conflicting reports have been presented regarding the malignant transformation of oral leukoplakia with epithelial dysplasia; however, we and some authors believe that epithelial dysplasia is an important factor in the malignant transformation of oral leukoplakia. The majority of researchers showed non-homogenous leukoplakia as a risk factor, although different terms have been used to describe these lesions. There may be several routes to malignant transformation of oral leukoplakia, including transformations induced by carcinogenesis due to betel quid chewing or smoking, or by HPV infection. While no definite treatment modalities for oral leukoplakia have been established, we suggest surgical therapy with an adequate safety-margin and well-timed evaluation as an appropriate treatment in preventing malignant transformation.

Analysis of Bilateral Neck Metastasis of Tongue Cancer / Oral Science International

To estimate the prognosis of bilateral cervical metastases from tongue carcinoma, we studied twelve patients (24-72 years old) who underwent neck dissections at our hospital to judge whether we should have performed radical treatment or not for those patients of tongue carcinoma who had bilateral metastatic nodes.The five-year survival rate of bilateral neck metastasis patients was 58% (the Kaplan-Meier method). On the other hand, the five-year survival rate of patients with only unilateral neck metastases of squamous cell carcinoma of the tongue was 56%. Thus, there was no statistical significant difference in survival rate.We conclude that even if a patient has metastatic lymph nodes on both sides of the neck, radical therapy should be done.

Perception of Hypernasality and its Physical Correlates / Oral Science International

To clarify the relationship between the perceptual diagnoses of hypernasality and its physical correlates, we conducted three experiments using the Japanese vowel /i/. We performed a spectral analysis of hypernasality on five cleft palate patients and six velum resection patients to investigate the spectral features related to hypernasality (experiment 1). Psychoacoustic experiments were conducted using various spectrally modified vowels to investigate the relationships between the spectral features and auditory perceptions of hypernasality (experiment 2). We analyzed the estimated spectral envelopes using an articulatory speech synthesis model to clarify the relationship between the spectral features and the velopharyngeal opening (experiment 3). Experiments 1 and 2 suggested four spectral features as the characteristics of hypernasality: (1) broadening of the F1 bandwidth, (2) an additional peak at around 1 kHz [P1], (3)^* a decrease in the magnitude of F2, and (4)^* a dip between F2 and F3 [D2]. In particular, the simultaneous modification of the decrease in the magnitudes of F2 and D2 is a very important cue for the auditory perception of hypernasality. Experiment 3 showed that the dips caused by nasal coupling resulted in the spectral modifications. In addition, the dip regions appeared to spread from the low-frequency region (around F1) to the high-frequency region (above F2), as the velopharyngeal opening enlarged. This suggests that the decrease in the magnitude of F2 and the dip between F2 and F3 [D2] are related to excessive acoustic coupling of the nasal cavity.^* New findings.