Yasuyuki Shibuya

Localization ofN-cadherin in the normal and regenerating nerve fibers of the chicken peripheral nervous system

Abstract The localization of N -cadherin in the normal, and regenerating nerve fibers was investigated by immunocytochemistry in the chicken sciatic nerve. The normal unmyelinated fibees exhibited N -cadherin immunoreactivity on the plasma membranes of axons and Schwann cells where they were in contact with each other, while myelinated fibers displayed no immunoreactivity except at the mesaxon where Schwann cell plasma membranes were attached to each other. In the regenerating nerves, intense immunoreactivity was demonstrated on the surface of plasma membranes of axons and Schwann cells where axon-axon and axon-Schwann cell contacts were made. No immunoreactivity was observed on the plasma membranes where regenerating axons or Schwann cells were in touch with the basal lamina. In addition, it was revealed that some vesicles in the growth cones had distinct N -cadherin immunoreactivity at the inner limiting membrane surface. These findings indicate that N -cadherin may be involved in the axon-axon and axon-Schwann cell adhesion in the normal unmyelinated as well as regenerating nerve fibers, and also in the attachment of Schwann cell processes at the mesaxon of myelinated fibers. In addition, these findings suggest that N -cadherin might be, at least in part, supplied by fusion of growth cone vesicles with the surface plasma membranes in growing axons.

Premalignant melanocytic dysplasia and malignant melanoma of the oral mucosa

Although malignant melanoma of the oral cavity frequently arises in pre-existing melanosis of the oral mucosa, little is known about oral melanoma precursor lesions. We reviewed three patients with premalignant melanocytic dysplasia and 14 with malignant melanoma of the oral mucosa. Thirteen of the 14 malignant melanoma cases had radial growth phases similar to those of acral lentiginous melanoma (ALM) of the skin. The prognosis of oral melanoma was not poor in contrast to that of cutaneous melanoma. Premalignant melanocytic dysplasia of the oral mucosa showed lentiginous or pagetoid proliferation of atypical melanocytes in the lower epithelium in the central part of the lesion, and lentiginous proliferation of dendritic melanocytes or simple hyperpigmentation in the basal cell layer in the peripheral part. These findings were similar to those of the radial growth phase of ALM of the oral mucosa.

Tumor-doubling time and onset of pulmonary metastasis from adenoid cystic carcinoma of the salivary gland

Adenoid cystic carcinoma (ACC), an uncommon malignancy in the head and neck region, invades diffusely and often metastasizes to the lung, although the growth rate is very slow. A retrospective study was conducted in 30 patients with ACC to ascertain the frequency of pulmonary metastasis, the doubling time of metastatic tumor deposits, and the time of onset for pulmonary metastasis. The following results were obtained: (1) Of 30 patients with ACC, 21 had pulmonary metastases (4 initially and 17 during observation), 7 were free of metastases but have not been observed for 5 years, and 2 were free of metastases for more than 5 years but less than 10 years after the initial treatment. The cumulative metastasis rate at 5 and 10 years for this group of patients was 70% and 100%, respectively. (2) Patients with T1 or T2 tumors that have a tubular or cribriform histopathologic pattern showed pulmonary metastases about 20 months later than those with T3 or T4 tumors and a solid pattern. However, the final metastasis rate did not differ between the 2 groups after a long period. (3) The tumor doubling time of the metastatic deposits of ACC was 86 to 1064 days with an average of 393 days, which was much longer than that of most other malignant neoplasms reported previously. (4) The time of onset of pulmonary metastasis was calculated to be much earlier (average of 227 months) before the first visit. These findings suggest that the treatment method for ACC should be chosen with the consideration that many of the patients may have occult pulmonary metastases at the time of their initial evaluation.

Ror2 expression in squamous cell carcinoma and epithelial dysplasia of the oral cavity

In this study, the expressions of Ror2 in the normal mucosa, the epithelium dysplasia, and squamous cell carcinoma (SCC) of the oral cavity were investigated, and possible differences in the expression patterns of Ror2 and of p53, Ki67, or PCNA were examined. In Western blotting analyses, Ror2 expression in oral cancer was significantly higher than that in the normal oral mucosa. Immunohistochemically, Ror2 was localized on the plasmalemma and in the rough endoplasmic reticulum (rER). The tissue area with an Ror2-positive expression tended to differ from the area with a positive expression of p53, ki67, or PCNA, and the number of cells with an Ror2 expression tended to increase as the degree of malignancy rose in the epithelial tissues. These results suggest that Ror2 was not related to cell proliferation, but rather associated with cell polarity and cell motility, and that it was also closely associated with the degree of malignancy in oral epithelial tissue.

Clinical evaluation of Lugol's iodine staining in the treatment of stage I–II squamous cell carcinoma of the tongue

Oral squamous cell carcinoma (OSCC) is often surrounded by epithelial dysplasia; leaving it unresected can result in local recurrence. Staining with Lugols iodine solution detects epithelial dysplasia in oral mucosa, but whether it decreases local recurrence after OSCC surgery is unknown. This study investigated local recurrence rates in patients with early tongue cancer who underwent surgery using Lugols staining. 93 patients with T1-2N0 tongue SCC underwent partial glossectomy using Lugols staining during surgery. Resection was performed at least 5mm from the margin of the unstained area. Patients were investigated retrospectively for local recurrence status. Postoperative histology revealed negative surgical margins for SCC or epithelial dysplasia in 81 patients, close margins for SCC in 5, positive margins for mild epithelial dysplasia in 6, and a positive margin for SCC in one. Those with a positive or a close margin for SCC underwent additional resection 2-4 weeks after surgery; one was proved histologically to have residual SCC. No patients developed local recurrence, but 2 died of neck metastasis and 2 of distant metastasis. The 5-year disease specific survival rate was 93.8%. Lugols staining during surgery can reduce local recurrence and improve survival in patients with early tongue SCC.

Risk factors associated with inferior alveolar nerve injury after extraction of the mandibular third molar—a comparative study of preoperative images by panoramic radiography and computed tomography

In this study we investigated the relationships among the risk factors for inferior alveolar nerve injury (IANI), and the difference between preoperative imaging findings on panoramic radiographs and computed tomography (CT), by univariate and multivariate analyses. We determined the following to be significant variables by multivariate analysis: panoramic radiographic signs, such as the loss of the white line of the inferior alveolar canal or the diversion of the canal; excessive haemorrhage during extraction; and a close relationship of the roots to the IAN (type 1 cases) on CT examination. CT findings of type 1 were associated with a significantly higher risk (odds ratio 43.77) of IANI. In addition, many panoramic findings were not consistent with CT findings (275 of 440 teeth; 62.5%). These results suggest that CT findings may be able to predict the development of IANI more accurately than panoramic findings. Panoramic radiography alone did not provide sufficiently reliable images required for predicting IANI. Therefore, when the panoramic image is suggestive of a close relationship between the impacted tooth and the IAN, CT should be recommended as a means of conducting further investigations.

Constitutional mutation of keratin 13 gene in familial white sponge nevus

OBJECTIVE We sought to investigate a novel mutation in the keratin genes assumed to be responsible for a familial case of oral white sponge nevus. PATIENTS AND METHODS The affected family consisted of a 36-year-old woman, her 17-year-old daughter, and her 14-year-old son. Keratin 4 and 13 genes extracted from venous blood lymphocytes were amplified by using the polymerase chain reaction and directly sequenced. RESULTS Sequencing analysis of the 3 patients revealed the presence of a novel heterozygous T-to-C transition mutation in exon 1 of the keratin 13 gene, with no abnormalities detected in the keratin 4 gene. CONCLUSION We identified a novel heterozygous missense mutation at 332T>C in the keratin 13 gene believed to be related to the development of white sponge nevus.

The observational study of delayed wound healing after tooth extraction in patients receiving oral bisphosphonate therapy.

INTRODUCTION In this study, we investigated whether such a discontinuation of oral bisphosphonate (BP) for 3 months might influence the incidence of BP-related osteonecrosis of the jaw (BRONJ) and wound healing after tooth extraction in patients receiving oral BP therapy. MATERIAL AND METHODS There were a total of 434 teeth in 201 patients (18 males and 183 females). The patients were divided into two groups depending on whether or not they underwent a 3-month discontinuation of BP therapy (BP- and BP+) before tooth extraction. In this observational study investigated delayed wound healing after tooth extraction in patients receiving oral BP therapy. RESULTS In all cases of the BP- group, there were no BRONJ although there was delayed wound healing in two cases. However, in one case of the BP+ group, oral BP was continued because it was deemed high risk to discontinue treatment by the patients physician. In this case, an intraoral fistula was still present with bone exposure at 120 weeks after extraction (BRONJ stage 1). CONCLUSION This study supports the idea of a drug holiday and encourages further clinical research on this topic of tooth extraction in patients receiving oral BP therapy.

Treatment and prognosis of malignant melanoma of the oral cavity: preoperative surgical procedure increases risk of distant metastasis

OBJECTIVE Many authors have reported that oral melanoma patients showed much worse prognosis than those with cutaneous melanoma. We investigated treatment method and prognosis of patients with oral malignant melanoma. STUDY DESIGN Twenty-one patients with oral melanoma treated at our hospital were investigated, with special reference to the influence of preoperative surgical procedures such as biopsy, incision, or tooth extraction on the prognosis. RESULTS All patients underwent surgery followed by immuno-chemotherapy with dimethyl triazeno imidazole carboxamide (DTIC), ninustine hydrochloride (ACNU), vincristine (VCR), and biologic response modifier OK-432. Local control was obtained in 20 of 21 patients. Lymph node metastasis appeared in 13 patients, but neck failure was not detected in any patients. Distant metastasis occurred in 9 patients in spite of loco-regional control. Five-year survival rate of 12 patients with no preoperative surgical procedure was 91.7%, while that of the 9 patients who had undergone surgical procedures before treatment was 25.9% (P < .05). CONCLUSIONS Oral melanoma patients can obtain a prognosis as good as that for cutaneous melanoma patients, when the above-mentioned therapy is used without any preoperative surgical procedures.

Evaluation of T-classifications of upper gingival and hard palate carcinomas—a proposition for new criterion of T4

Most carcinomas of upper gingiva and hard palate are classified as T4 stage on the basis of the UICC criteria, since they easily invade the underlying bone tissue. We classified 43 patients with squamous cell carcinoma of the upper gingiva in terms of three criteria: (1) the original T-classification by UICC, (2) the classification by the Japan Society for Head and Neck Cancer (JSHNC), and (3) a new classification in which the maxillary sinus or nasal floor is used as the defining borderline for T4 (MSF classification). Our study demonstrated that the new classification was superior with regard to distribution of patients by T stage, correlation with prognosis and choice of treatment method.