1-Hexylcarbamoyl-5-fluorouracil (HCFU) is a masked compoud of 5-fluorouracil (5-FU), which is known to release 5 -FU spontaneously. We previously reported that the antitumor effects of HCFU were enhanced by combination with hyperthermia. In this study, we investigated the most effective treatment schedule and the enhancement of the antitumor effect of thermochemotherapy by combination with cepharanthin for tumor targeting therapy.
Ehrlich ascites tumor cells were transplanted to the right food pad of mice, and the antitumor effect was evaluated on the basis of tumor volume on the 21st day after transplantation. 5-FU concentration in the tumor tissue was also analyzed by high performance liquid chromatography (HPLC) as described by Mori et al.
The results were as follows. The highest concentration of 5 -FU in tumor tissue and the greatest enhancement of antitumor effect was found in mice treated with HCFU before hyperthermia, as compared with mice receiving hyperthermia before HCFU administration. Cepharanthin enhanced the antitumor effect of HCFU combined with hyperthermia.
The results indicated that HCFU given 1 to 2 hours before hyperthermia was the most effective treatment schedule. In addition, cepharanthin was considered to be useful as a biochemical modulator for clinical thermochemotherapy.

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We studied the optimal timing for the enhancement of the antitumor effects of the CDDP analogue cis-diammine-1, 1-cyclobutane dicarboxylate platinum (II)(CBDCA) combined with hyperthermia against CD-1 mice bearing Ehrlich ascites tumor (EAT) cells in vivo and the effect of hyperthermia on drug influx and efflux in vitro. The tumor doubling time was prolonged when two modalities were combined. The longest tumor doubling time was obtained by the simultaneous use of CBDCA and hyperthermia. The findings indicated that the most effective treatment was the simultaneous use of CBDCA and hyperthermia. An increase in the intratumoral platinum concentration was obtained by simultaneous treatment with CBDCA and hyperthermia.
Ehrlich ascites tumor cells were used in cellular accumulation studies with a flameless atomic absorption spectrophotometer. The cells were incubated in the serum-free RD medium. After 1 hour of exposure to 40μg/ml CBDCA (final concentration), the influx at 42.5°C was approximately 2 -fold higher than control (37.0°C incubation). After 1 hour of exposure to CBDCA at 37.0°C or 42.5°C, the rate of efflux in the 5 % calf serum RD medium at 37.0°C or 42.5°C was measured after drug removal. There was a significant difference between the control group (uptake and efflux at 37.0°C) and the heated group (uptake and efflux at 42.5°C), but no significant difference between the control group and the treatment group (uptake at 42.5°C and efflux at 37.0°C). We concluded that hyperthermia increases the intracellular accumulation of CBDCA.

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Fifty-two patients with squamous cell carcinomas of the oral cavity, oropharynx, and maxillary sinus who underwent neck dissection were clinico-pathologically reviewed. Maxillary sinus and tongue carcinomas showed high incidences of lymph node metastases. In contrast, carcinomas of the lower gum and oropharynx had low incidences of lymph node metastases. Of the 36 cases with histologically positive nodes, level 2 was the most frequent site of metastases followed by level 3, level 1, and level 4 at the affected side. Metastasis contralateral to level 2 was not infrequently observed. Non-contiguous nodal sites were observed in 2 patients with bilateral metastases. The largest number of metastatic nodes was 18, but the largest proportion of cases in this series had only one positive node. There was some correlation between the number of involved nodes and the level of metastasis. In relation to T category, many of the T 1 cases had only one affected node, but the numbers of involved nodes varied considerably in T2, T3 and T4 cases. The cumulative 5-year survival rate was 86.7% in pN (+) cases, versus 62.4% in pN (-) cases, and this difference was significant (P<0.05). Patients with more than 6 involved nodes showed a poor 5-year survival rate (14.7%). There was no statistical significance in 5-year survival between immediate dissection and subsequent therapeutic dissection.
The metastatic nodes were classified into 3 types according to the localization of tumor nests: marginal type, paracortical type, and replaced type. The replaced type accounted for 60% of all affected nodes, the paracortical type for 30%, and the marginal type for 10%. In the marginal type and the paracortical type, the majority of nodes were 9 mm or less in maximum diameter. In contrast, the replaced type nodes were 10mm or more in maximum diameter. Capsular invasion and extranodal spread were observed primarily in the replaced type. Extranodal spread was not found in the marginal type. The 5-year survival rate for patients with capsular invasion or extranodal spread without fibrous thickening of the nodal capsule was much poorer than those with fibrous thickening. The results suggest that fibrous thickening of the nodal capsule may inhibit the extension of extranodal spread. Independent of the tumor nest localization within the node, juxtacapsular tumor emboli of the metastatic nodes were observed in 17.1% of all metastatic nodes, and the 5 year survival rate for these cases was low.

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In this study, we immunohistochemically investigated the expression of TGF-β in 16 human temporomandibular joint (TMJ) discs.
The specimens were obtained at discectomy and autopsy.
TGF-β showed three types of expression:(1) at the blood cells in capillaries;(2) around fibrocytes and at the lacunae of chondrocytes in the disc; and (3) at the stroma of the hyperplastic synovial membrane and proliferating synovial membrane.
The first two types were observed in all cases, including control.
The last type was seen only in internal derangement of the TMJ.
The results suggest that TGF-β is involved in the pathogenesis of synovitis.

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Methicillin-resistant Staphylococcus aureus (MRSA) is one of the most important microorganisms in nosocomial infections. We surveyed inpatients with MRSA in our department to develop measures for preventing further outbreaks of MRSA infection and compared the distribution of MRSA in our department with that in the entire hospital.
The following results were obtained:
1. In our department, MRSA were isolated from 11 hospitalized patients with advanced head and neck cancer between January 1992 and June 1995.
2. The incidence of MRSA isolated from pus was higher than that from other specimens, such as sputum and urine.
3. General infections caused by MRSA, developed in 4 of the 11 patients, but none of them died of MRSA infection.
4. Most of the cancer patients in whom MRSA was detected died of cancer in a relatively short period, suggesting a relationship between MRSA infection and a poor prognosis in cancer patients.
5. Seventeen strains of MRSA were isolated from 8 inpatients in our department, and were studied using various epidemiological markers.
6. On the basis of drug sensitivity, coagulase typing, enterotoxin typing, and the ability to produce TSST-1, the MRSA strains in our ward were classified into 4, 2, 4 and 3 types, respectively.
7. At least 3 to 4 types of MRSA, including an “epidemic” type of MRSA, were isolated from 5 of 8 inpatients in our ward.
8. Except for no MRSA susceptible to OFLX, the current status of MRSA infection in our ward was similar to that of the entire hospital.
Because some MRSA carriers are discharged and followed up as outpatients, the complete eradication of MRSA appears to be very difficult.

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The relationship between root canal filling and the periodontal healing of autotransplantated teeth was studied clinically and radiographically in 21 autotransplanted teeth with complete root formation that were followed up for more than 6 months. The teeth were classified into three types according to the status of root canal filling immediately after transplantation: type A) teeth with root canal (s) wide enough to be detected on radiographs and root canal filling (s) to the apex (es); type B) teeth having incomplete root canal filling (s) because of narrow root canal (s); and type C) teeth having root canal (s) detectable on radiographs but with incomplete filling (s). The periodontal healing was examined more than 6 months postoperatively. Ten teeth classified as type A had no clinical symptoms and showed regeneration of the periodontium on radiographs. Eight teeth classified as type B had no clinical symptoms but the periodontal spaces were indistinct in 5 teeth. No clinical symptoms were associated with 2 of 3 teeth classified as type C, but the periodontal spaces were not clearly seen in the apical regions. The presence of apical lesions and inflammatory resorption of the root was observed on radiographs of the other tooth. These findings suggest that periodontal healing is associated with the width of the root canal and the status of root canal filling.

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Papillary cystadenomas usually occur in the ovary, testis, and thyroid gland and rarely arise in the oral and maxillofacial region. We recently encountered a patient with a papillary cystadenoma of the parotid gland. The patient was a 54-year-old woman who complained of a painful swelling of the right parotid region. Clinically, the lesion was an elastic soft, fluctuant mass, about 30×20mm in size and localized at the right parotid gland. Facial nerve paralysis was not evident. CT, MRI, and ultrasound examinations were performed. The clinical diagnosis was a parotid cyst or a benign tumor. The lesion was totally excised with the superficial part of the gland under general anesthesia. Histopathologically, the lesion had some cyst cavities with multiple papillary projections into the cystic spaces. The wall was lined with pseudostratified oxyphilic cells arranged in two layers. There were no lymphoid follicles in the connective tissue. The histopathological diagnosis was papillary cystadenoma. Papillary cystadenoma is a benign tumor, but recurrence has been reported. There has been no evidence of recurrence in the patient as of 17 months after the operation, but long-term followed-up will be continued.

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We reported two cases of calcifying epithelioma arising in subcutaneous tissue around the auricle. One case was in a 11-year-old Japanese girl who visited our clinic complaining of a mass at the left preauricular region, which had been present since the age of 3. Radiographic examination revealed the presence of calcification measuring 10×8 mm in diameter. Enucleation was performed, and a histopathological diagnosis of a calcifying epithelioma was made. Histopathologically, the tumor was composed mainly of shadow cells, and bone formation was also observed. The other case was in a 52-year old Japanese man, who visited our clinic complaining of a mass at the left side of the neck. The tumor was located at the subauricular region, and the surface of the tumor had undergone partial necrosis. The tumor was enucleated with the surrounding granulation tissue. The histopathological diagnosis was a calcifying epithelioma. Histopathological examination revealed the tumor to be composed of basophilic cells and shadow cells; calcifications were also observed.
The postoperative course of both patients was uneventful, with no evidence of recurrence.

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Two cases of rhabdomyosarcoma arising in the maxilla were treated at our hospital.
Case 1: A 28-year-old woman complaining of swelling in the right submandibular region. Several biopsies were performed to establish a diagnosis because of difficulty in histological evaluation. The patient was treated with radiation and anticancer agents without success and died 9 months after initial treatment.
Case 2: A 15-year-old girl presented with a tumor in the right upper maxilla that extended through the right antrum. Pathologic examination showed a variety of small round cells. Multiple-drug chemotherapy and radiotherapy were employed. The patient died 16 months after initial treatment.

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Synovial chondromatosis is a metaplastic lesion. It occurs frequently in the knee, elbow, and hip joints. However, reports of synovial chondromatosis of the temporomandibular joint (TMJ) are rare. This paper describes a case of synovial chondromatosis of the TMJ.
A 24-year-old woman visited our hospital complaining of difficulty in opening mouth. Double-contrast arthrography, CT scan, and MRI revealed a radiopaque mass measuring about 20 mm in front of the right condyle. Removal of the lesion, discectomy, and synovectomy were performed under general anesthesia. The lesion was consisted of 87 particles, the largest of which measured, 21×18×11mm. The patient has been free of disease and functional disturbances of the TMJ for two years after surgery.

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Granular cell tumor is a rare benign tumor arising in various soft tissues of the body. Its pathogenesis is not clearly understood.
We report our experience with a 23-year-old woman, with a granular cell tumor arising in the margin of the tongue.
A mass arising in the left margin of the tongue was resected along with the peripheral soft tissue under local anesthesia. Recurrence was not found 3 months after resection. The microscopic pathological diagnosis was granular cell tumor.
Recent reports provide compelling evidence for the neurogenic hypothesis of granular cell tumors. The neurogenic hypothesis was also supported by our case because the granules in the granular cells were positively stained by the PAS reaction. In addition, immunohistochemical studies showed a positive reaction with the antibody against S-100 protein.
Six-patients (20-59 years old; mean age, 33.4 years old; 3 men, 3 women) have been given a diagnosis of “granular cell tumor” at our clinic during the past 20 years. All of these cases of granular cell tumor were found in the tongue.

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Lingual osseous choristoma is a very rare lesion first described as osteoma of the tongue by Monserrat. We present a case of osseous choristoma arising in the tongue of a 7-year-old girl. The lesion was a hard polypous mass measuring about 3.5×5.5mm, near theforaman caecum of the tongue. The mass was removed under general anesthesia.
Histological examination showed a well circumscribed mass of dense lamellar bone with Haversian canals. The mass was covered with normal squamous epithelium.

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Eosinophilic granuloma of soft tissue is characterized by swelling with peripheral eosinophilia and elevated serum IgE values. The main histopathological features are proliferation of lymph folliculoid structures, granulation tissue with marked infiltration of eosinophils and mast cells, and fibrosis.
We describe a case of eosinophilic granuloma of the soft tissue of the left buccal region that was accompanied by urticaria recidivans. We also summarize our current understanding of the cause, disease concepts, and treatment of this disease.

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Wegener's granulomatosis (WG) is a systemic disease Characterized by necrotizing granulomatous inflammation of the respiratory tract, kidney, and other organs. The most common initial symptom of this disease is necrotizing granuloma in the nasal and paranasal cavity, and oral lesions are rare. Here we report a case of WG associated with oral lesions as one of the initial symptoms. The patient was a 39-year-old man who was referred to Fukuroi Municipal Hospital because of nasal pain, nasal obstruction, chest pain, pyrexia, gingival swelling, and ulcers of the tongue and soft palate. On the basis of clinical, laboratory, and histopathological findings, a diagnosis of WG was made, and the patient was treated with a combination regimen of chemotherapy regimen of chemotherapy consisting of prednisone and cyclophosphamide. The patient responded very well to the treatment, and symptoms disappeared within 4 weeks. He remains free of any oral or systemic signs and symptoms as of 11 months after the initiation of treatment.

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In this study, we investigated the proliferating activity of odontogenic keratocysts in 6 cases of basal-cell nevus syndrome by immunohistochemical studies using the proliferating cell nuclear antigen (PCNA) monoclonal antibody. The results were as follows.
1. PCNA-positive cells were detected on the basal cell layer and suprabasal cell layer in the epithelial linings, rete peg formations, or satellite cysts of odontogenic keratocysts. PCNApositive cells were widely distributed in the epithelial layer, especially in epithelial islands.
2. Odontogenic keratocysts had a significantly higher PCNA labeling index than that of radicular cysts, used as control, especially in epithelial islands.
These results strongly suggest that odontogenic keratocysts in basal-cell nevus syndrome have high proliferating activity.

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We report a case of mucosal cyst of the maxillary sinus with extensive maxillary bone resorption. A 47-year-old man was referred to our clinic with a chief complaint of a swelling in the left cheek.
Radiography revealed a dome-shaped radiopaque shadow at the floor of the left maxillary sinus.
The cyst was resected.
Histopathological examination revealed a mucosal cyst of the maxillary sinus.
Postoperatively, there has no evidence of recurrence as of one and a half years after the operation.

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A case of radiation osteomyelitis of mandible in a 56-year-old man with acquired factor VIII inhibitor is presented. He had undergone radiation therapy for malignant lymphoma of the tonsilar region seven years earlier, and also had received steroids to treat acquired factor VIII inhibitor for a year. On initial examination, he was given a diagnosis of phlegmon of the cheek caused by pericoronitis of the left lower wisdom tooth. To prevent the recurrence of inflammation, the wisdom tooth was extracted carefully, but radiation osteomyelitis occurred in association with a pathological fracture of the condylar head. After mini-pulse therapy with methylpredonisolone, segmental mandibulectomy and reconstruction with a titanium metal plate were performed. The postoperative course was satisfactory with no complications such as bleeding or infection.

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We report a case of necrotizing lymphadenitis arising in the left submental and submandibular regions of a 26-year-old woman.
The patient was referred to our clinic for evaluation of a slight fever and swellings in her left submandibular region. Ultrasonic examination and CT scan revealed multiple swellings of lymph nodes in the region. Treatment with antibiotic and anti-inflammatory drugs was ineffective. A biopsy specimen was therefore taken from the submental region. The histological findings were compatible with a diagnosis of necrotizing lymphadenitis. Systemic steroids was then given, and the symptoms disappeared about one month after the initiation of treatment. The patient was observed for two years without any signs of recurrence.
The anti-EBV antibody titer suggests that EBV may be involved in the pathogenesis of this disorder.

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Angioneurotic edema (Quincke's edema) is characterized by localized swelling of sudden onset and rapid disappearance in the oral and facial region. Some cases may be associated with respiratory distress, caused primarily by laryngeal edema. Angioneurotic edema can be classified into hereditary type and nonhereditary type. Most cases are nonhereditary type, and the pathogenesis is unknown.
We report a case of angioedema in the tongue and oral floor that was probably caused by treatment with an angiotensin-converting enzyme (ACE) inhibitor. The patient was a 64-year-old woman with a history of hypertension, diabetes, and hyper cholesterolemia. Her chief complain was swelling and an abnormal sensation of the tongue. Her family history was unremarkable. Laboratory examinations showed no abnormalities other than hyper cholesterolemia. We prescribed chlorpheniramine maleate, but angioneurotic edema was poorly controlled. One month later she complained of dyspnea and swelling. We gave methylprednisolone and stopped the ACE inhibitor that she was taking. Subsequently, chlorpheniramine maleate was switched to tranexamic acid.
There has been no recurrence of symptoms as 4 years after the termination of ACEinhibitor treatment.

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A five-year-old boy with kabuki make-up syndrome and submucosal cleft palate associated with mental retardation was not treated surgically because his parents did not consent to oral and maxillofacial therapy. He was therefore equipped with a speech aid. After practice. his voice progressively improved.

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