Etsuhide Yamamoto

Mode of invasion, bleomycin sensitivity, and clinical course in squamous cell carcinoma of the oral cavity

Forty patients with squamous cell carcinoma of the oral cavity were treated with bleomycin prior to undergoing surgery. The degree of the clinical effect of bleomycin and the postoperative clinical course of each case were estimated from the viewpoint of correlation with the mode of invasion. A strong correlation was found among the mode of invasion, bleomycin sensitivity, and clinical course. A slight effect of bleomycin and poor prognosis existed in the group with a diffuse invasion of mode of invasion, while the greatest effect of bleomycin and good clinical course were achieved in the group with a welldefined tumor‐host borderline.

Immunohistochemical study of tumour angiogenesis in oral squamous cell carcinoma

To assess the clinical significance of angiogenesis in oral squamous cell carcinoma (SCC), we examined vessel density immunohistochemically in 44 primary oral SCCs using the JC-70A antibody which reacts specifically with vascular endothelial cells. In addition, the expression of vascular endothelial growth factor (VEGF) and its receptors, KDR, Flt-1 and Flt-4 in oral SCCs was examined in relation to the vessel density and lymph node metastasis. There was no association of vessel density with tumour site, T-category (tumour size), degree of differentiation or cervical lymph node metastasis, except that the vessel density of carcinomas with a well-defined tumour-stromal boundary was higher than that of diffusely invasive carcinomas. The intensity of VEGF expression correlated with lymph node metastasis (P < 0.01), but not with vessel density. The expression of KDR and Flt-1 did not correlate with vessel density and lymph node metastasis. However, the vessel density in Flt-4-positive carcinomas was higher than that in Flt-4-negative carcinomas (P < 0.05), and expression of Flt-4 most significantly correlated with lymph node metastasis (P < 0.001). These results suggest that the expression of VEGF or Flt-4 rather than vessel density may be a predictor of lymph node metastasis in oral SCC.

Factors affecting the occurrence of bacteremia associated with tooth extraction

This study examined the factors that affect the occurrence of bacteremia associated with tooth extraction and the kinds of bacteria causing this bacteremia. Bacteremia was found in 132 (72.1%) of 183 patients who had one or more teeth extracted for various reasons. Bacteremia occurred more frequently when teeth were extracted because of inflammatory dental diseases. The occurrence of bacteremia also increased with the number of teeth extracted and the age of the patients. When the volume of blood lost during surgery was > 50 ml and the time required for the operation exceeded 100 min, the occurrence of bacteremia was also higher. Anaerobes were isolated from 104 (78.8%) of the 132 cases of bacteremia. Of the 187 isolates obtained, three (1.6%) were aerobes, 51 (27.3%) were facultative anaerobes (including microaerophils), and 133 (71.1%) were anaerobes. Among facultative anaerobes and microaerophils, the most frequently isolated bacterial genera were Lactobacillus (n = 15), Streptococcus (n = 13), and Staphylococcus (n = 12); and among anaerobes, Eubacterium (n = 40), Peptostreptococcus (n = 40), and Propionibacterium (n = 20).

Cloning of a human gene potentially encoding a novel matrix metalloproteinase having a C-terminal transmembrane domain.

Matrix metalloproteinases (MMPs) play key roles in tissue remodeling during physiological and pathological processes by degrading various extracellular matrix (ECM) components. Although nine distinct MMPs have been characterized by cDNA cloning, there are thought to be more corresponding to the complexity of the ECM. MMP genes expressed in human tissues and cell lines were analyzed by the polymerase chain reaction (PCR) using degenerate primers that corresponded to the conserved amino acid (aa) sequences of the MMPs. One isolated complementary DNA (cDNA) fragment had sequence homology to the reported MMPs, but was otherwise unique. A human placenta cDNA library (Clontech) was screened using the fragment as a probe and a 3.4-kb cDNA fragment containing a long open reading frame (potentially encoding 582 aa) was isolated. The putative gene product had a common domain structure and the conserved sequence of a MMP, but it had a unique transmembrane (TM)-like structure at the C terminus. It should, therefore, be an TM protein, whereas all the other reported MMPs are secretory proteins. Thus, the gene is thought to be the first of a new subclass of MMPs whose products are potentially expressed on the cell surface.

A comparative CT evaluation of pharyngeal airway changes in class III patients receiving bimaxillary surgery or mandibular setback surgery

OBJECTIVE The purpose of this study was to compare the morphologic changes of the upper airway space in Class III patients who underwent mandibular setback or bimaxillary surgery (maxillary advancement and mandibular setback) by computed tomography at 2 levels: soft palate and base of tongue. METHODS The sample consisted of 47 subjects in 2 groups who had been diagnosed as having Class III skeletal deformities and had been treated by mandibular setback or bimaxillary surgery (maxillary advancement and mandibular setback). Anteroposterior, lateral, and cross-sectional area dimensions of the airway at the level of soft palate and base of tongue were measured pre- and postoperatively on computed tomography images. RESULTS Anteroposterior dimensions of the airway decreased in both groups (P < .0001); however, the reduction was significantly less in cases treated with bimaxillary surgery (P < .05). In the mandibular setback surgery group, the cross-sectional area of the airway decreased significantly (P < .001). Although the cross-sectional area of the airway decreased in the bimaxillary surgery group, the reduction was not statistically significant (P > .05). CONCLUSIONS This study suggests that bimaxillary surgery can prevent narrowing of the upper airway in the correction of Class III deformities in comparison with mandibular setback surgery used as the sole treatment. Computed tomography was valuable in determining the effects of surgical treatment on pharyngeal airway dimensions.

Immunohistochemical localization of a urokinase-type plasminogen activator system in squamous cell carcinoma of the oral cavity: association with mode of invasion and lymph node metastasis.

The binding of urokinase-type plasminogen activator (uPA) to its receptor (uPAR) has been implicated in cancer invasion and metastasis. This activity is known to be regulated by several inhibitors such as plasminogen activator inhibitors (PAIs). To elucidate the participation of the uPA system in the malignant behaviour of squamous cell carcinoma (SCC) in the oral cavity, uPA, uPAR, PAI-1 and -2 expression and localisation in 34 primary oral cancers were examined immunohistochemically. The results were then compared with clinicopathological findings. The positive rates of uPA, uPAR, PAI-1 and -2 expression were 23.5, 29.4, 29.4 and 11.8%, respectively. uPA expression correlated with mode of cancer invasion according to Yamamoto-Kohamas criteria (p < 0.01) and with secondary regional lymph node metastasis. uPAR expression also correlated with mode of invasion. In particular, the tumours of both uPA- and uPAR-positive [uPA(+)/uPAR(+)] cases were highly invasive. In the present study, neither PAI-1 nor PAI-2 expression correlated with clinicopathological parameters. However, PAI-2 negative cases of uPA(+)/uPAR(+) were significantly more invasive (p < 0.0001). Such uPA(+)/uPAR(+)/PAI-2(-) cases almost always showed secondary lymph node metastasis (p < 0.01). These results indicate that the uPA system plays a significant role in the invasive and metastatic processes of oral SCC, and that this system may be a powerful aid in evaluating the clinical course or prognosis of patients with oral cancer.

SIGNIFICANCE OF STROMAL DESMOPLASIA AND MYOFIBROBLAST APPEARANCE AT THE INVASIVE FRONT IN SQUAMOUS CELL CARCINOMA OF THE ORAL CAVITY

Tumor invasion involves complex interactions between tumor and stromal cells. We examined the extent of connective tissue in the tumor stroma and whether myofibroblasts play a role in assisting cancer invasion and metastasis.

Development of a new invasion and metastasis model of human oral squamous cell carcinomas.

A new model was devised in order to establish an in vivo model for oral carcinoma that exhibits significant local invasion and metastasis. One hundred and fifty-two nude mice had tumour cells from one of two established oral squamous cell carcinoma (SCC) cell lines (OSC-19 and OSC-20) implanted into the tongue or the oral floor via an intra-oral route and, as a control, the subcutaneous tissue of the back. The back tumours showed an expansive growth pattern, lacking significant invasion of surrounding tissues. In contrast, the tumours implanted into the tongue or the oral floor exhibited invasive growth and the histological appearance was similar to that of the original tumours. Moreover, regional neck lymph node and pulmonary metastases were observed in this model. Regional neck lymph node metastases were detected in 81.0% of mice implanted with OSC-19 cells and in 13.6% of mice implanted with OSC-20 cells. OSC-19 and OSC-20 cells showed pulmonary metastases in 9.5 and 9.1% of mice, respectively. These results suggest that this intra-oral implantation model is valuable in the study of the mechanism of invasion and metastasis of oral SCC.

The use of polylactic acid/polyglycolic acid copolymer and gelatin sponge complex containing human recombinant bone morphogenetic protein-2 following condylectomy in rabbits.

PURPOSE To examine the results of a polylactic acid/polyglycolic acid copolymer and gelatin sponge complex (PGS) with or without recombinant human bone morphogenetic protein-2 (rhBMP-2) used to treat condylar defects in rabbits. MATERIAL AND METHODS Adult male Japanese white rabbits (n=60; 3kg; 12-16 weeks old) were divided into three groups of 20 each. All rabbits underwent condylectomy. In the two implanted groups, PGS with or without 5 microg of rhBMP-2 was implanted to the condylar defect without fixation. No material was implanted into the control group. Animals were sacrificed at 2, 4, 8, 12 and 24 weeks postoperatively, and the temporomandibular joints (TMJs) were examined histologically. RESULTS Four weeks after implantation, growth of bone and cartilage-like tissue was observed in all rabbits that received PGS implants (with and without rhBMP-2). A cartilage-like layer was derived from the bone marrow at the operated surface. There was no growth of bone tissue in the control rabbits, but they also had a cartilage-like layer directly derived from the operated surface. CONCLUSION This study demonstrated that PGS with or without rhBMP-2 could induce regeneration of new bone and cartilage-like tissue in the TMJ.

The effect of mandibular setback or two-jaws surgery on pharyngeal airway among different genders

Cephalometric studies show significant gender differences in the size of the pharyngeal airway space. This study aimed to investigate and compare morphologic changes after mandibular setback or two-jaws surgery on the pharyngeal airway in men and women using computed tomography (CT). The sample included 34 women and 13 men diagnosed with Class III skeletal deformities, who had been treated by mandibular setback or bimaxillary surgery (maxillary advancement and mandibular setback). Anteroposterior, lateral and cross-sectional area dimensions of the airway, at the level of soft palate and base of tongue, were measured pre- and postoperatively on CT images. In the mandibular setback group, the anteroposterior and cross-sectional area of the pharyngeal airway at the level of the soft palate and base of tongue were significantly reduced for men or women (P<.05). In the two-jaws surgery group, only midsagittal anteroposterior dimensions at the same levels were significantly decreased for men or women (P<.05). The difference between any values measured between men and women who received bilateral sagittal split ramus osteotomy setback surgery or two-jaws surgery for the treatment of class III anteroposterior discrepancy were not statistically significant (P>.05). This study suggests that oropharyngeal airway measurements, important for airway patency, do not demonstrate sex dimorphism.