Surgical approaches for condylar fractures related to facial nerve injury: deep versus superficial dissection.

The aim of this study was to investigate the probability of facial nerve injury (FNI) in the treatment of condylar neck and subcondylar fractures (CN/SCFs) with percutaneous approaches and to identify factors predicting FNI. The data of 80 patients with 87 CN/SCFs were evaluated retrospectively. The primary outcome was FNI occurrence. The predictor variables were age, sex, aetiology, alcohol consumption, fracture site and pattern (dislocation or not), concomitant fractures, time interval to surgery, surgeon experience, plate type, and the dual classification of percutaneous approaches. The approaches were classified based on whether subcutaneous dissection traversed the marginal mandibular branch (MMB) deeply (deep group: submandibular and retroparotid approaches) or superficially (superficial group: transparotid, transmasseteric anteroparotid (TMAP), and high cervical-TMAP approaches). Twenty-two patients (27.5%) suffered FNI, of whom two in the deep group had permanent paralysis of the MMB. In the multivariate logistic regression model, deeply traversing surgery approaches (odds ratio 12.4, P=0.025) and the presence of a dislocated fracture (odds ratio 6.66, P=0.012) were associated with an increased risk of FNI. These results suggest that percutaneous approaches in the superficial group should be recommended for the treatment of CN/SCFs to reduce the risk of FNI.

Small size of metastatic lymph nodes with extracapsular spread greatly impacts treatment outcomes in oral squamous cell carcinoma patients.

Extracapsular spread (ECS) of metastatic lymph nodes from oral carcinoma is the most significant prognostic predictor of a poor treatment outcome. However, only a few reports on prognostic factors in ECS-positive cases have been investigated. To address this problem, a detailed examination of ECS pathology was conducted to determine the prognostic factors of oral squamous cell carcinoma (OSCC) with ECS of metastatic lymph nodes. This study involved 63 OSCC patients with at least one pathologically metastatic node with ECS. Among the 229 metastatic lymph nodes, 149 exhibited ECS. Univariate analysis revealed that a poor outcome and recurrence were significantly associated with the number of ECS-positive nodes, density of ECS, and the minor axis of the smallest ECS-positive node. However, multivariate analysis identified only small size of ECS-positive nodes as a significant and independent factor predicting recurrence and a poor outcome. Thus, small size of ECS-positive nodes is the most important prognostic indicator for OSCC with ECS in metastatic lymph nodes. The classification of ECS status using the minor axis of ECS-positive nodes may be useful for further prediction of a poorer prognosis in OSCC cases. Standardization of ECS diagnosis and multicenter prospective studies will be required to confirm and refine these findings.

First signs of late-presenting cervical lymph node metastasis in oral cancers during follow-up.

One of the most important prognostic factors in oral squamous cell carcinoma (OSCC) is the presence of lymph node metastasis. Therefore, the early detection of late-presenting cervical lymph node metastasis is important. Although many studies have assessed diagnostic modalities for detecting metastatic cervical lymph nodes, no study has evaluated the process, especially first signs, for detecting late-presenting cervical lymph node metastasis. A retrospective analysis comparing methods for detecting the first signs of late-presenting lymph node metastasis was performed. A total of 65 OSCC patients were assessed. These patients were identified retrospectively as having presented late metastasis during follow-up after initial treatment with curative intent. The findings of four detection methods were analyzed: palpation, ultrasonography, computed tomography, and subjective symptoms. The numbers of cases identified by each method were as follows: palpation, 31 (47.7%); ultrasonography, 17 (26.1%); computed tomography, 12 (18.5%); and subjective symptoms, 5 (7.7%). Palpation played a major role in the discovery of late-presenting lymph node metastasis. In contrast, metastatic lymph nodes were detected by other methods in about half of the cases. The results suggest a possible stratification of the various methods used for metastatic lymph node detection, depending on the characteristics of individual cases.

Aperture width of the osteomeatal complex as a predictor of successful treatment of odontogenic maxillary sinusitis.

Odontogenic maxillary sinusitis (OMS) is an inflammatory disease caused by the spread of dental inflammation into the sinus. The long-term administration of antibiotic medicine and/or treatment of the causative tooth are the usual initial treatments. These initial treatments are not always effective, and the reason is not well understood. The purpose of this study was to identify factors of significance that may contribute to the results of the initial treatment of OMS. Thirty-nine patients were studied, divided into two groups according to the results of initial treatment: effective or non-effective. The effective group comprised 20 patients who were cured by initial treatment. The non-effective group comprised 19 patients who required an additional operation. The duration of symptoms, spread into the other sinuses, aperture width of the osteomeatal complex (OMC) on the side of the maxillary sinus, and anatomical variations in the sinuses were compared between the groups. The only significant difference found was in the aperture width of the OMC, which was significantly narrower in the non-effective group than in the effective group. The aperture width of the OMC may be a significant predictor of the effectiveness of initial treatment of OMS.

Stabilization of phenotypic plasticity through mesenchymal-specific DNA hypermethylation in cancer cells.

The epithelial-mesenchymal transition (EMT) has a crucial role in normal and disease processes including tumor progression. In this study, we first classified epithelial-like and mesenchymal-like oral squamous cell carcinoma (OSCC) cell lines based on expression profiles of typical EMT-related genes using a panel of 18 OSCC cell lines. Then, we performed methylation-based and expression-based analyses of components of the Wnt signaling pathway, and identified WNT7A and WNT10A as genes silenced by mesenchymal-specific DNA hypermethylation in OSCCs. A significant association was revealed between some clinicopathological findings and the DNA methylation status of WNT7A (normal vs tumor, P=0.007; T1-2 vs T3-4, P=0.040; I-III vs IV, P=0.016) and WNT10A (N0-N1 vs N2-N3, P=0.046) in the advanced stages of OSCC. Moreover, we found that E-cadherin expression in cancer cells may be positively regulated by WNT7A, whose expression is negatively regulated by mesenchymal-specific DNA hypermethylation or ZEB1 in mesenchymal-like OSCC cells. Our findings indicate that epithelial-specific gene silencing through mesenchymal-specific DNA hypermethylation may stabilize the phenotypic plasticity of cancer cells during EMT/MET.

Epidermal growth factor receptor gene copy number aberration at the primary tumour is significantly associated with extracapsular spread in oral cancer.

BACKGROUND: Extracapsular spread (ECS) of lymph node metastasis in head and neck cancers, including oral squamous cell carcinomas (OSCCs), is known to reflect tumour aggressiveness, and is significantly associated with high rates of loco-regional recurrence, distant metastasis, and poor outcome. The purpose of this study was to confirm ECS as an important prognostic indicator and to determine the significant factors associated with ECS in OSCCs. METHODS: We investigated the incidence of ECS and impact of ECS on survival in 127 OSCC patients. To determine the factors significantly correlated with ECS, we examined many factors, including the clinicopathological features of primary tumours, lymph node metastasis, and copy number aberrations of the cyclin D1 gene (CCND1) and epidermal growth factor receptor gene (EGFR) at primary tumours, and evaluated the value of predicting the risk of ECS of the metastatic lymph node. RESULTS: Kaplan-Meier and multivariate disease-free and overall survival analysis clearly demonstrated that ECS is an independent prognostic factor in OSCCs. Moreover, logistic regression analysis showed that the number of pathologically positive nodes and copy number aberrations of EGFR at the primary tumour are independent predictors of ECS. CONCLUSIONS: The findings suggest that ECS is an independent prognostic factor in OSCCs. Moreover, the number of pathologically positive lymph nodes and EGFR numerical aberrations of the primary tumour were also shown to be excellent predictors of ECS in OSCCs. Preoperative evaluation of EGFR numerical aberrations might therefore be a useful tool for selecting patients at high risk of ECS, who would benefit from targeted aggressive multimodality therapy.

Homozygous deletions on the short arm of chromosome 3 in human oral squamous cell carcinomas.

Recent cytogenetic and allelic deletion analyses have demonstrated that deletions on the short arm of chromosome 3 (3p) are frequently found in various cancers, including oral squamous cell carcinomas (OSCCs). This suggests that one or more tumor suppressor gene(s) for these malignancies might be located on 3p. In the present study, to further define the region(s) on 3p that harbor putative tumor suppressor gene(s) for OSCCs, we have investigated the existence of homozygous deletions (HDs) at 34 loci on 3p, in 14 OSCC cell lines. HDs were detected within the FRA3B region at 3p14.2 in only two cell lines (HSC-4 and TSU). Recently, the human fragile histidine triad (FHIT) gene was isolated from this region, abnormalities of which have been found at high frequencies in several types of human cancers. We also examined the expression of the FHIT gene, using reverse transcription-polymerase chain reaction (RT-PCR) and exon-specific PCR, in the two OSCC cell lines which showed HDs at 3p14.2. There was no detectable expression of exon 5, which was the first protein-coding exon of FHIT gene, in HSC-4 cells, indicating that this region was homozygously deleted in this cell line. On the other hand, HD in the TSU cells did not affect the coding region of the FHIT gene, and the wild-type transcript was detected by RT-PCR. Therefore, several candidate tumor suppressor genes, including the FHIT gene, may reside in these homozygously deleted regions. To our knowledge, this is the first report of HDs on 3p in OSCCs.

A case of false median cleft of upper lip with IV-A holoprosencephaly that underwent cheiloplasty at 2.5 years of age.

Holoprosencephaly results from the incomplete development of midline structures within the cerebrum and encompasses a series of abnormalities of mid-facial development. Here, we report a case of male holoprosencephaly associated with false median cleft of upper lip. This patient belonged clinically to the DeMyer's group IV holoprosencephaly, semilobar type. An infant with this type of holoprosencephaly has been thought to die generally within 1 to 2 years after birth and to rarely benefit from an operation. In this case, the patient had cheiloplasty at the age of 2.5 years at the request of his parents and he lives currently, being 3 years and 2 months old.

Inactivation patterns of the p16 (INK4a) gene in oral squamous cell carcinoma cell lines.

To determine whether inactivation of the p16 gene mapped to the chromosome 9p21 region is associated with the development of oral squamous cell carcinoma (SCC), we investigated the mutational states of two forms of alternative transcripts (alpha and beta) from the p16 gene in 14 oral SCC cell lines by means of RT-PCR, PCR, direct sequencing and methylation analyses. Alterations of the alpha transcript were detected in all of the cell lines examined: homozygous deletions in three lines; subtle mutations in exons 1 alpha or 2 in four lines; skipping of exon 2 in two lines; hypermethylation of the 5' CpG island of the p16 gene in four lines; and an unknown mechanism in one line. On the other hand, abnormalities of the beta transcript were observed in seven of the 14 cell lines. Nonetheless, the mutations that essentially affect the function of the encoded protein were found only in five cell lines, including three lines with homozygous deletion. There was no cell line having only beta transcript alterations. Thus, alteration of the alpha transcript of the p16 gene was a highly frequent event in oral SCC. Since this type of alteration resulted in gene inactivation through multiple pathways, it may play a major role in the process of oral SCC development.

Functional evidence for involvement of multiple putative tumor suppressor genes on the short arm of chromosome 3 in human oral squamous cell carcinogenesis.

Cytogenetic and restriction fragment length polymorphism (RFLP) analyses have suggested that a putative tumor suppressor genes(s), which may play an important role in the development of human oral squamous cell carcinoma (SCC), is located on the short arm of chromosome 3 (3p). We previously reported that introducing in intact human chromosome 3 into three different oral SCC tumorigenic cell lines completely suppresses the tumorigenicity of each cell line with significant decrease in the in vitro growth rate and morphological changes. To map the tumor suppressor gene(s) on 3p, we have now examined the tumorigenicity of microcell hybrid clones containing various fragments derived from 3p that were introduced by microcell-mediated chromosome transfer. Sixteen hybrid clones were obtained from four successful experiments, and these clones were classified into two groups: 4 fully tumorigenic clones and 12 suppressed phenotype clones. Analyses of the 3p segments in the series of hybrid clones with the use of RFLP or microsatellite markers revealed that the 3p21.2-p21.3 or 3p25 regions or both were consistently retained in the 12 clones with suppressed phenotype but not in the 4 tumorigenic clones. The more proximal 3p13 region also was retained in three nontumorigenic clones. The overall results are fairly compatible with recent evidence that there are three discrete regions on 3p showing frequent allelic losses on oral SCC, and they directly provide functional evidence for the presence of tumor-suppressor genes for oral SCC in these regions. The possibility that three genes, FHIT, VHL, and T beta R-II, recently identified on 3p may be significantly involved in oral SCC development is also discussed.

Suppression of tumorigenicity in three different cell lines of human oral squamous cell carcinoma by introduction of chromosome 3p via microcell-mediated chromosome transfer.

It has been suggested that loss of the short arm of chromosome 3 is one of the most frequent abnormalities in human head and neck cancers including oral squamous cell carcinomas (SCC) and that one or more putative tumor suppressor gene(s) which may contribute to the initiation and/or progression of these tumors might be located on chromosome 3p. In this study, we examined the effects of introducing human chromosome 3 or 7 by microcell hybridization on the tumor-associated phenotypes of three different human oral SCC cell lines, HSC-2, HSC-3 and HSC-4. Transfer of a single chromosome 3p completely suppressed the tumorigenicity of all three parental cell lines, which showed a significant decrease in growth rate in vitro and morphological changes. In contrast, transfer of chromosome 7 had no effect on HSC-2 and HSC-4 cells, although it suppressed the tumorigenicity of HSC-3 cells without modifying their in vitro growth properties. Our findings provide additional confirmatory evidence that loss or inactivation of putative tumor suppressor gene(s) present on chromosome 3p might be primarily involved in the development of human oral SCC. The possibility that chromosome 7 may carry another tumor suppressor gene(s) is also discussed.