From May 1994 to March 1995, 18 patients with head and neck cancer were treated with accelerated hyperf ractionated irradiation and concomitant use of daily low-dose carboplatin. Tumors were located in the maxillary sinus, the hypopharynx in five patients, respectively, the tongue in four, the larynx in two and the tonsil, the buccal mucosa in one, respectively. The median age was 60.5 years (range, 38-70). All patients had biopsy-proven squamous cell carcinoma. According to TNM stage (UICC 1987), T3N0 in 5 patients, T4N0 in 7, T3N1 in one, T3N2 in two, T4N2 in one and T4N3 in two, respectively. All patients were treated with 1.6Gy, twice daily, 10 times a week, with minimum interval of 6 hours between fractions and the total tumor dose to 70.4Gy. Carboplatin was administered intravenously 15-30 minutes before irradiation at a dose of 30mg/body/day. The median follow-up period was 6.7 months with a range of 2-12 months. Complete response was observed in 9 patients (50%), partial response was observed in 8 patients (45%). Only one patient with maxillary sinus carcinoma showed no response. Major toxicities, graded according to RTOG criteria were stomatitis and bone marrow suppression. Grade 2-3 stomatitis were observed in 17 patients and Grade 4 was observed in just one patient. Grade 3-4 thrombocytopenia were observed in 22% of all patients, but none of the all was critical.

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We evaluated the results of radiation therapy in three cases with skull base spread and/or metastasis from salivary gland tumors. The period from primary diagnosis to skull base recurrence ranged from 28 to 120 months (mean 80), and the time from which neurological symptoms appeared to radiation therapy was from 8 to 12 months (mean 10). A decrease in tumor size and relief from symptoms were achieved in all cases. The period of relief from symptoms ranged from 4 to 12 months (mean 8.3). There were no serious complications following radiation therapy. Although most malignant tumors originating from the salivary glands have been thought to be radioresistant, palliative radiation therapy for skull base spread and/or metastasis effectively improves the patient's quality of life.

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The efficacy of concomitant Cisplatin (CDDP) and radiotherapy on locally advanced head and neck cancer was evaluated. This approach of concurrent use may allow enhancement of tumor cell kill, decrease of acute side effects and other adverse effcts compared with adjuvant or neoadjuvant combination chemotherapy. This study was a result of comparison between the group of chemoradiation and the other combination chemotherapy including a large dose of CDDP as a historical control study.
Protocol 1: Chemoradiation (Apr. 1992-Dec. 1995). Twenty seven patients have been treated with concurrent CDDP (20mg/m², over 4 times a week) administration during one week or two separate weeks of radiotherapy.
Protocol 2: Combination chemotherapy including a high dose of CDDP combined with radiotherapy (Jul. 1983-May. 1993). Thirty seven patients have been treated with CDDP (80mg/m²) and two selected chemotherapeutic agents among PEP (10mg/m², over 4 days), MTX (40mg/m²) and 5-FU (500mg/m²).
The patients treated with Protocol 1 had a superior local control of 23/27 (85%) compared with 16/37 (43%) in patients treated with Protocol 2. 2-year relapse free survival and 2-year overall survival of the Protocol 1 were 58%, 100% respectively. The same as those survivals of the Protocol 2 were 56%, 65% respectively. There is a significant difference between relapse free survival curves of the each group (p=0.049), and also a difference between overall survival curves of them (p=0.021). The group of CDDP chemoradiation was also lower than the controle group concerning with the rate of side effects. Although this study was historical and observating duration was still short, concurrent CDDP chemoradiotherapy was suggested to be effective method of treatment for locally advanced head and neck cancer.

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Dose volume histograms of the high dose rate brachytherapy for 30 patients with tongue cancer and 6 patients with cancer of the mouth floor were calculated by means of PLATO. All patients were treated with HDR brachytherapy of 6Gy per day. 20 patients with tongue cancer and 4 patients with mouthe floor cancer were treated with 60Gy/10 fractions of HDR brachytherapy alone. Other 12 patients were treated with 20-41Gy of external radiation and 42-60Gy of HDR brachytherapy. V100% was defined as the volume of 6Gy per fraction.
For tongue cancer, V100% of patients treated with single plane, single plane plus one tube, double plane and volume implant were 14cm³, 29cm³, 18cm³ and 64cm³, respectively. The corresponding figures of V200% were 3cm³, 8cm³, 3cm³ and 10cm³. V100% and V200% of mouth floor cancer were 10cm³ and 3cm³.
For patients treated with HDR brachytherapy alone, local recurrence occurred in 2 patients with small treatment volume (V100%: 9.7cm³, 11.0cm³) and soft tissue ulcer occurred in 2 patients with large treatment volume (V100%: 25.6cm³, 31.8cm³). Treatment volumes of mouth floor cancer were small compared with tongue cancer patients. There were no soft tissue ulcer in 6 patients.
For 10 tongue cancer patients treated with combination of external radiation and HDR brachytherapy, 6 patients were treated with single plane implant and 4 patients with volume implant. For single plane implant, V100% and V200% were 13-19cm³ and 2.3-4.3cm³, respectively. There were no local recurrence and no soft tissue ulcer. For volume implant, V100% and V200% were extremely high compared with other treatment. Ulcer occurred in the patient without local recurrence. It is difficult to treat these bulky tumor without late complication.
Treatment volume is an important factor for both local control and late complication.

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The development of tumor cell drug resistance is a major obstacle which often leads to the failure of cancer chemotherapy. We studied the cytotoxic and pharmacological properties of 40°C hyperthermia and CDDP in CDDP-sensitive (IMC-3) and CDDP-resistant (IMC-3-DDP) human maxillary carcinoma cells. IMC-3 and IMC-3-DDP cells did not differ in heat sensitivity at 40°C. Heating at 40°C potentiated CDDP cytotoxicity in both IMC-3 and IMC-3-DDP cells with thermal chemoenhancement ratios (C. E. R.) of 1.48 and 1.94, respectively. The intracellular CDDP uptake level of IMC-3-DDP at 37°C was significantly reduced to about 60% compared with IMC-3 cells. At 40°C, however, hyperthermia increased platinum accumulation by factors of 1.4 and 1.8 in IMC-3 and IMC-3-DDP cells, respectively. CDDP sensitivity was hyperthermically chemopotentiated in CDDP-resistant variants rather than in the control clones.
Thus, clinical cancer chemotherapy with CDDP may be improved by an appropriate combination with hyperthermia even at 40°C.

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Purpose: Usually, the middle-aged patients with non-Hodgkin's lymphoma and concomitant other adult diseases can not be tolerable for intensive chemotherapy. Then we introduced a new regimen composed of radiation for local and sorrounding lymph node areas, and brief reduced-dose chemotherapy into treatment for such patients.
Subjects and Methods: Thirth-eight patients with Stage IE or Stage IIE non-Hodgkin's lymphoma of the Waldeyer's ring were a core of this study. Histopathologically they were diagnosed as diffuse intermediate grade. In addi-tion, they suffered from other adult diseases such as cardiovascular diseases, cereblovascular disorders, diabetus melitus, chronic liver diseases, etc. They were treated by the combined modality composed of reduced-dose chemo-therapy (70%-ACOP: 2 cycles or 70%-MACOP-B: 8 weeks) and regional lymph node irradiation (30Gy) puls boost irradiation (10Gy) to inolved area (total 40Gy).
Results: No relapses were observed in the radiation field, the 5-year disease-free survival rate and cause-specific survival rate for all patients were 85.7% and 91.4%, respectively. There were no differences of the 5-year disease-free survival rate between stage I_E and II_E, among the pathological subtypes, among the complications and etc.
Conclusion: The regimen composed of regional lymph node irradiation (30Gy) puls boost irradiation (10Gy) to involved area (total 40Gy) and reduced-dose chemotherapy (70%-dose ACOP, 70%-dose MACOP-B) is a safe and useful approach to treatment for diffuse intermediate grade of B cell lymphoma in middle-aged patients having other adult diseases.

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We have established a squamous cell carcinoma cell line (SCCNI) in a protein-free medium consisting of 1:9 mixture of Dulbecco's modified Eagle's medium (DMEM) and MCDB 153, and purified an autocrine growth factor from the conditioned medium. One protein was isolated from the protein-free conditioned medium by using heparin affinity, strong anion exchange, gel filtration, and reversed phase chromatography. Analysis of SDS-page electrophorosis revealed that molecular weight of the protein was approximately 25kDa under the non-reduced condition, and 15kDa under the reduced condition. In Westernblotting analysis, the 25kDa protein was reacted by the anti-inhibin β A antibody. These results indicated that the 25kDa protein is Activin A. We also detected expression of inhibin β A mRNA in this squamous cell carcinoma line by RT-PCR. These results suggested that this squamous cell carcinoma cell line produces Activin, which may act as an autocrine growth factor for the proliferation of squamous carcinoma cells.

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Griffonia simplicifolia agglutinin-II (GSA-II) staining following endo-β-galactosidase (E-β-G) digestion procedure was applied on cells of three papillary carcinomas extracted by fine needle aspiration, and cells obtained by stamping five papillary carcinomas, two adenomas and five normal tissues adjacent to tumors excised at surgery. The results demonstrated that all the clusters of cells and almost all the separated two or three cells from eight papillary carcinomas were stained with GSA-II following E-β-G digestion. The cells from two adenomas and five normal thyroid tissues had no reactivity with GSA-II following E-β-G digestion. These results are well consistent with the previous ones using formalin-fixed, paraffin-embedded tissue sections. Applying the procedure of GSA-II staining following E-β-G digestion to cells collected by fine needle aspirate would be useful means to distinguish thyroid papillary carcinomas from other types of thyroid tumors before operation.

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In the period of 1984 to 1995, ultrasound examinations were performed on 144 patients (12 were recurrent cases) with pleomorphic adenoma (PA) and 10 patients with carcinoma in pleomorphic adenoma (CPA) of the parotid gland. According to our ultrasonographical diagnosis criteria of the parotid gland tumors, the benignity of the tumors (primary cases) were assessed correctly in 125 (94.7%) of 132 patients with PA. Five patients (50%) with CPA diagnosed as malignant. Total accuracy rate of the diagnosis of 142 tumors was 91.5%. In 4 cases of recurrent pleomorphic adenomas showed malignant patterns. The accuracy of sonography in predicting beniginity is affected by tumor size, namely, tumors smaller than 2cm in diameter were all diagnosed as benign. Benign or malignant pattern was examined retrospectively by the boundary echo and internal echo, respectively. The finding of boundary echo of the PA showed benign pattern in 111 cases out of 132, and that of CPA showed malignant pattern in 3 cases out of 10. And the finding of internal echo of the PA showed benign pattern in 120 cases out of 132, and that of CPA showed malignant pattern in 6 cases out of 10. The strong echos, that are sign of malignant pattern, were seen in 70% of CPA, and in 13.6% of PA. We analyzed ultrasonograms compared with pathological findings of tumors. Sharpness of the boundary echo is not directly related to the thickness of the tumor capsule. The origin of the strong echo was supposed to be the presence of dense fibrous tissue, chondroid formation, and hyaline degeneration areas. It is difficult to diagnose the subtype of the PA by means of ultrasonogram.

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α-Catenin (α-cat), one of the E-cadherin (E-cad) associated cytoplasmic proteins regulates E-cad functions. Since the expression of E-cad has been suggested to contribute metastasis of the same type of tumor, I hypothesized that the examination of α-cat may also help to evaluate an ability of tumor to metastasize. In the present study, therefore, the expression of α-cat in oral squamous cell carcinomas (SCCs) obtained by biopsy from 58 patients was examined with the immunohistochemistry of using a monoclonal antibody and was analyzed the relationship between the staining patterns and the regional lymph node metastasis, then those were compared with that in E-cad. α-Cat visually localized as circumferential staining and/or cytoplasmic staining in SCC cells. The expression of α-cat was divided positive, weakly positive and negative. The incidence of metastasis to regional lymph nodes in the negative case of α-cat was significantly higher (70.0%) than that in the combined group of the positive and the weakly positive cases (31.6%) (p=0.0118). The 65.5% (38/58) of E-cad staning belonged to the weakly positive case and the incidence of lymph node metastasis in this group was 47.4% (18/38) which was almost equal to that in all 58 cases (26/58, 44.8%). This result suggests that the rate of lymph node metastasis could not be supeculated in more than half of the patients. By adding the results of α-cat staining examination, α-cat negative case out of the weakly positive case for the E-cad showed higher incidence of lymph node metastasis than the weakly positive case.
In conclusion, the combined examination of α-cat and E-cad expression in oral SCC will yield useful information concerning regional lymph node metastasis.

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The binding of urokinase-type plasminogen activator (uPA) to its receptor (uPAR) has been implicated in cancer invasion and metastasis. This enzyme controls the synthesis of the plasmin, which is widely acting serine proteinase, from the zymogen plasminogen. To elucidate the participation of the uPA system in the malignant behavior of squamous cell carcinoma (SCC) in the oral cavity, uPA and uPAR expression and localization in 34 primary oral cancers were examined immunohistochemically. The results were then compared with clinicopathological findings. The positive rates of uPA and uPAR expression were 23.5 and 29.4%, respectively. The staining pattern of uPA was very similar to that of uPAR. uPA expression correlated with mode of cancer invasion according to Yamamoto-Kohama's criteria. uPAR expression also correlated with mode of invasion. In particular, the tumors of both uPA and uPAR-positive [uPA (+)/uPAR (+)] cases were highly invasive. These results indicate that the uPA system plays a significant role in the invasive and metastasic 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.

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During the past 25 years, 14 cases with head and neck cancer underwent bilateral ligation of the internal jugular vein. We studied complications, prognosis, surgical risks and clinical effect of bilateral ligation in these cases. There was no difference in complications and prognosis between the group of simultaneous bilateral ligation and that of separate ligation. It was suggested that bilateral ligation of the internal jugular vein was a feasible surgical approarch in selected cases.

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For the characteristic diagnosis of the cervical lymph node by ultrasonography, we investigated the 39 metastatic lymph nodes in papillary carcinoma of the thyroid gland and 24 nonmetastatic nodes in benign disease with 10MHz transducer. We examined these nodes on size (long and short axis diameter), shape (short/long axis diameter ratio), and internal echo (echo level, punctate bright echogenic spots, hilus echogenic line, cystic pattern). The short axis diameter and nodal shape of metastatic nodes were more thick and spherical respectively than those of nonmetastatic ones. The internal echo level of the metastatic nodes was more high than the nonmetastatic ones. Of the 39 metastatic nodes, 79% exhibited punctate bright echogenic spots, on the other hand none of the 24 nonmetastatic nodes showed the spots. Ourresults indicated that the hilus echogenic line was not present in any metastatic nodes, but was seen 58% of nonmetastatic ones. Of the 39 metastatic nodes, 41% exhibited a cystic pattern, none of the 24 nonmetastatic nodes showed a cystic pattern. We think that these different findings between metastatic and nonmetastatic nodes can be valid criteria for the characteristic diagnosis of the cervical lymph node by ultrasonography.

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The prognosis of oral squamous cell carcinoma and the histopathology of the primary lesions and metastasic neck lymph nodes were studied in 138 patients who underwent radical neck dissection (155 sides). The results suggested the importance of radical as well as prophylactic neck dissection in the initial operation and the usefulness of functional neck dissection. General indications of this procedure are considered to be (1) N1 cases with no metastasis in the trigonum cervicale posterius, (2) N2 cases showing no signs of external capsule invasion in internal jugular vein lymph nodes, (3) N0 cases suspected to have metastasis from the type of invasion, and (4) cases requiring bilateral radical neck dissection.

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Transitional cell carcinoma in the nasal cavity and paranasal sinuses are thought to be rare. Between 1981 to 1995, we treated 4 cases of transitional cell carcinoma in the nasal cavity and paranasal sinuses. These subjects were consisted of 4 males and ranging in age between 24 to 62 (mean age 45.5). The origin of 2 cases were the nasal cavity, the others were the ethomid sinus. Three cases were treated with combind therapy consisting of surgery, radiotherapy and chemotherapy. A case was treated with irradiation alone.

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Hematogenous metastatic mechanism of head and neck carcinoma cell is unknown. We analyzed the adhesion of tumor cell to endothelial cells in vitro. The number of adhering carcinoma cells to human umbilical vein derived endothelial cells (HUVECs) stimulated by TNF-α was much more than that to resting HUVECs. Treatment of stimulated HUVECs with anti-E-selectin monoclonal antibody (mAb) reduced the number of adhering carcinoma cells to endothelial cells. However, treatment with anti-P-selectin, anti-VCAM-1 and anti-ICAM-1 mAbs could not reduce the number of carcinoma cells. Furthermore, treatment of carcinoma cells with anti-sialyl-Lewis X and anti-sialyl-Lewis A mAbs decreased the amount of adhering carcinoma cells. Thus, the interaction of E-selectin expressed on endothelial cells with sialyl-Lewis X and siayl-Lewis A expressed on carcinoma cells play an important role in carcinoma cell adhesion to endothelial cells.
Treatment of carcinoma cells with E-selectin chimeric protein could increase the amount of adhering carcinoma cells to fibronectin. This data indicated that carcinoma cell adhesion to E-selectin molecules expressed on endothelial cells could activate the ligand of fibronectin. This activation is a part of the adhesion cascade in carcinoma cell adhesion to endothelium.

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Preoperative and postoperative upper gastrointestinal endoscopy combined with esophageal iodine staining was performed in a total of 116 patients with head and nedk cancer (68 males and 48 females), and esophageal cancer was detected in 7.8% (8 males and 1 female) of the total. An unstained area as a result of the iodine staining considered necessary for follow-up was found in 25.9% (22 males and 8 females) of the total number of patients, and stomach cancer was detected in 2.6% (2 males and 1 female) of the total. When esophageal cancer and stomach cancer were totaled, double cancer was found in 12 of the 116 patients, an incidence of 10.3%. The frequency of occurrence of double cancer was investigated according to T classification, mode of invasion, and degree of differentiation of the primary tumor. According to T classification, most of the cases were T2 or T3, and relatively few were T4. Investigation of mode of invasion failed to reveal and relationship between severity of grading of malignancy and frequency of occurrence of double cancer. According to differentiation, occurrence was most common in the poorly differentiated type. Smoking and alcohol drinking were also investigated in the patients in whom esophageal diseases were confirmed by endscopy. Smoking and alcohol drinking seemed to play a large role in the development of both head and neck cancer and double caner of the esophagus and stomach.

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37 patients with oropharyngeal cancer (30 males and 7 females) were treated in our clinic during the ten years from 1985 to 1994. Their mean age was 63.1 years old ranged from 38 to 84. They were classified in 3 of T1, 21 of T2, 9 of T3 and 4 of T4, and also in the stage clasificasions, stage I was one cases, stage II 14 cases, stage III 8 cases and stage IV 14 cases respectively. 5-year survival rate by stages was 0% for stage I, 36.5% for stage II, 65% for stage III and 34.4% for stage IV in all cases. Primary lesion death was the most high frequency of 50%. It was possible to control the primary lesion in T1 cases either radiotherapy or surgical treatment. In T2 cases, control of the primary lesion showed good result from the complementary operation rather than that of the non-surgical treatments. Carcinoma in the lateral wall is more effective than those in anterior and posterior wall and in superior wall by the radiotherapy. It was difficult to control the primary lesion by the radio-chemotherapy in T3 cases. From our data, if was no sensitive for radiation, We must be decide the surgery even in T1 and T2 cases. In T3 and T4 cases, it should be taken the functional reconstractive surgery following the component surgery with neck dissection after radiotherapy.

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Forty seven ultrasonography-guided fine needle aspiration cytology (USG-FNAC) were performed in patients with small neck tumors and the following results were obtained. The maximum diameter of the punctured tumors ranged from 6mm to 15mm.
1) Thirteen of 16 aspirates from malignant tumors were correctly diagnosed by USG-FNAC, establishing a sensitivity at 81%. All of 31 aspirates from benign tumors were correctly diagnosed by USG-FNAC, establishing a specificity at 100%, Consequently, overall accuracy of USG-FNAC was 94%.
2) USG-FNAC was very useful to diagnose thyroid carcinomas with small primary tumors, and recurrent lymphnode metastases of head and neck cancer in early stage.
3) The false-negative cases were 3 (mucoepidermoid carcinoma of submandibular gland, lymphnode metastasis of thyroid papillary carcinoma and lymphnode metastasis of nasopharyngeal carcinoma).
4) The reason of the false-negative is various and close communication between the clinician and the cytologist is crucial to decrease the false negative rate.

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From May 1994 to Aug 1995, 29 patiens with advanced head and neck cancer were treated with accelerated hyperfractionated irradiation (1.6Gy, twice daily, 10 times a week, with minimum interval of 6 hours between fractions and the total tumor dose to 70.4Gy) and concomitant use of daily low-dose Carboplatin (30mg/Body). The average age was 64.4 years (38-83). The median follow-up period was 15.5 months with a range of 2-27 months. Complete response and partial response were observed in 19 patients (65.5%), and 9 patients (31.0%), respectively. Total response rate was 96.5%. But no complete responder was observed in maxillay sinus cancer patients. The major acute toxicity was stomatitis which was mainly graded 2-3, but no therapeutic interruption was observed. Twenty-six patiens whose median follow-up period was over 3 months were evaluated for late sequelae. Grade 1-2 stomatitis was observed in 92.4% of all patients. Grade 1-2 xerostomia was observed in 70% of all patients. There was no difference between accelerated fractionation and conventional fractionation concernig late sequelae. It is doubtful whether to treat advanced maxillary sinus cancer and deep ulcerated hypopharyngeal cancer with this method. We experienced distant metastase even if the primary region has been controlled. Adjuvant chemotherapy will be requierd in the future.

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In generally, differentiated thyroid carcinomas are said that there are few numerical chromosomal aberrations. But, some cases in well differentiated thyroid carcinomas indicates aggressive invasion or metastasis. In this report, we tried to detect of numerical chromosomal aberrations about chromosome 1, 7, 17 on thyroid carcinomas by fluorescence in situ hybridization (FISH) and flow cytometry (FCM). In well differentiated thyroid carcinomas, no clear abnormality were not detected both in nuclear DNA contents and in numerical chromosomal aberrations. But, poorly differentiated thyroid carcinoma showed DNA-aneuploidy by FCM, and detected trisomy 7, tetrasomy 7 and trisomy 17 by FISH. Undifferentiated carcinoma showed DNA-aneuploidy, detected trisomy 1, tetrasomy 1 and trisomy 7, and suspected loss of short arm in chromosome 1.

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Treatment results of stage I glottic cancer in Gunma Cancer Center were analyzed from a viewpoint of radiation therapy. From 1972 to 1990, 128 patients with stage I glottic cancer were treated with radiation. Patient age ranged from 38 to 81, and there were only 7 women in this series. They were treated with daily fractions of 2.0-2.4Gy to total doses of 40-70Gy mainly with 6MV X-ray using lateral parallel opposing field.
Five and 10-year overall survival rate were 84% and 58%, respectively. The cause specific survival rate were 99% in 5 years, 96% in 10 years.
Twenty patients have locally recurred, and five and 10-year local control rates were 86% and 82%, respectively. All locally recurred patients received a salvage operation. Thirteen patients received partial laryngectomy, and total laryngectomy was adapted in 7 patients.
Uni-and multivariate analysis was performed using T stage, tumor size, total dose, field size, fraction size, and overall treatment time. Though it was not significant, extending the overall treatment time was assosited with a reduced local control rate.

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KTP laser, which can be easiliy operated has been used head and neck lesion. In this study we examined the effect of KTP laser on laryngeal disease; Laryngeal cancer, Leukoplakia, Granulomatosis.
When KTP laser is used, laser beams are irradiated to lesions observed from various angles using an endoscope at 0, 30, 70 degrees under a TV monitor instead of a microscope. After the field of view is maintained through an endoscope, using 0.3 and 0.6mm fibers mainly transpiration is made at 2-5W and occasionally an incision is added in cases of laryngeal cancer. Since satisfactory effects have been obtained in patients with cancer T1 (sometimes T2 cases), leukoplakia, granulomatosis of the larynx, KTP laser will be useful on head and neck lesion.

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We analyzed 74 vascular lesions experienced in our service from 1983 to 1996 with special reference to the modality of treatment, clinical course and prognosis of arteriovenous malformation (AVM). The objects are conformed of 60 cases of haemangioma, 6 of lymphangioma, 6 of AVM, 1 of Sturge-Weber syndrome and 1 of Wyburn-Mason syndrome. Surgical resection was predominantly selected for the treatment, except for the advanced AVM showing invasive growth into the mandible and facial skin because of high risk of massive bleeding and severe functional and aesthetic disturbance. Embolization was applied to the lesion preferably, however, suppression of the blood flow was not always satisfactory and permanent using conventional material such as Gelform, Ivalon and steel coil, follwing by reopening of the embolized blood vessel and/or the bypass formation. A patient suffering from repeated episodes of severe pain and bleeding from nidus finally died of sudden massive bleeding 4 years after uneffective embolization with conventional Gelform, Ivaon and steelcoils. On the contrary, excellent embolization was noted with n-butyl-2-cyanoacrylate (NBCA), though it is difficult to adjust its polymerizing time.

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Anchorage-independent growth of tumor cells as colonies in a semisolid medium is a good indicator of tumorigenicity. Many head and neck squamous carcinoma cell (HNSCC) lines fail to form colonies in agar or agarose. Matrigel is an extract from the Engelbreth-Holm-Swarm mouse sarcoma, a tumar rich in basement membrane and extracellular matrix proteins such as laminin, collagen IV, entactin and heparan sulfate proteoglycans. It also contains proteases (collagenases and plasminogen activators) and growth factors that include platelet-derived growth factor, insulin-like growth factor I, transforming growth factor β, epidermal growth factor, and lower amounts of basic fibroblast growth factor and nerve growth factor. Here we report that HNSCC SqCC/Y1 cells, which did not form colonies in 0.5% agarose, were able to form colonies when the cells were suspended in 0.2ml of Matrigel diluted 1:1 with growth medium and placed on the top of semisolid 1% agarose in growth medium.

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Immunohistochemical expression of bcl-2 protein and p53 protein was evaluated in 22 patients with early stage/intermediate grade B cell lymphoma of the Waldeyer's ring. The cases in which immunohistological reactivity for bcl-2 protein and p53 protein was observed in 15% or more of examined tumor cells were regarded as positive. Thirteen of 22 patients (59%) were of positive for bcl-2 protein. p53 protein was found to be positive in 10 of 22 patients (45%). Its prognostic significance was analysed in relation to relapse-free survival (RFS) and cause-specific survival (CSS). bcl-2 positive patients showed significantly worse prognosis as compared with bcl-2 negative patients. p53 protein expression was not correlated with the prognosis. Expression of bcl-2 protein was the significant prognostic factor in multivariate analysis.

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Radical neck dissection is able to resect the cervical tissue completely and certain to control cervical lymphnode metastasis, but postoperative injury is very great. Conservatie neck dissection (modified neck dissection or partial neck dissection) is available to decrease postoperative complaint, but is considered to have a high risk of cervical recurrence. In principle of National Cancer Center Hospital, therapeutic neck dessection is performed as conservatively as possible, only invasive tissue is resected. In order to evaluate this policy, prognosis of 127 cases of oral cancer with radical neck dissection was compared with that of 95 cases with conservative neck dissection since 1981 to 1990 in National Cancer Center Hospital retrospectively. Prognosis of radical neck dissection was 43.2% of 5 year survival, modified neck dissection and partial neck dissection (supraomohyoidal neck dissection) was 63.2% of 5 year survival. Local cervical recurrence (1.5%) of conservative neck dissection was less than that (11.0%) of radical neck dissection thogh recurrence of primary lesion or parapharyngeal space was even. Though N-stage of radical neck dissection was slightly more advanced than that of moified neck dissection and there was nonsense to check statistically significant difference between two groups, it is probable that modified neck dissection is not inferior to radical neck dissection in prognosis.

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Degradation of the extracellular matrix (ECM) surrounding tumor cells is an essential step for tumor invasion and metastasis. Matrix matalloproteinases (MMPs) that degrade various ECM components are frequently expressed in a variety of tumor tissue at higher levels than in their normal region. Type IV collagen is one of the major components of ECM, and its enzymatic degradation is initiated by MMPs, especially MMP-2 and MMP-9. In this study, investigated MMP-2 and MMP-9 concentration in cancer tissue homogenate of 49 cases with head and neck squamous cell carcinomas, and also measured MMP-2 and MMP-9 concentration of serum. Fresh tissue samples were obtined from 49 patients with carcinomas at the time of biopsy or surgery. The level of MMP-2 were about 2-fold higher in carcinoma tissue with lymphnode metastasis than in tissue without lymphnode metastasis. However, the level of MMP-9 in carcinoma tissue and both MMP-2 and MMP-9 concentration in serum showed no significant difference between cases with lymphnode metastasis and cases without lymphnode metastasis. These results suggest that MMP-2 plays an important role in tumor metastasis, so MMP-2 could be a useful biological marker to represent the metastasis and prognosis.

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Laryngeal cancer is one of the head and neck cancers with good prognosis. This is due to the morphological features of the larynx (laryngeal framework, elastic barriers) and the well established treatment modalities. Some patients, however, died from the cancer despite the treatment efforts. Among the 406 patients with laryngeal cancer who visited us between 1971 and 1996, 106 had died; 55 patients died from the primary cancer and the others from the other causes such as second primary cancers or cardiopulmonary diseases. Among the 55 patients who died from the primary cancer, 19 died from local recurrences, 19 from both local and distant metastases, 13 from distant metastases, and 4 from other causes. As for the 19 patients who died from local recurrences, we reviewed their surgical reports in light of whether there are factors prompted local recurrences. Direct invasion into the skin, extralaryngeal mucosal invasion, and major vascular invasion are the three patient's factors that might prompt local recurrences. Inadvertent manipulation to the cancer, lack of dissecting paratracheal lymphnodes, and insufficient resection margin are the three surgeon's factors that might prompt local recurrences.

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At Home Terminal Care Program is well indicated in the patients with the head and neck cancers because their general conditions usually remains fair until dying stage. We conducted At Home Terminal Care Program for five patients with terminal stage of the head and neck cancers. Problems and difficulties around this program are inquired of the family members of these 5 patients. Following points are considered to be important through this inquiry;
1. At Home Terminal Care Program should be commenced at early stage of terminal therapeutics.
2. Procedures for the topical treatment should be acquired by family members during a patient can attend as an outpatient.
3. Informed concent should be obtained for the fact that it would not always be possible to countermove to emergent state effectively under At Home Terminal Care Program.
4. Suicide should be warned.
At Home Terminal Care Program should be conducted widely because this program can maintain high quality of life of the patients who is in the terminal stage of the head and neck cancers.

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Loss of heterozygosity (LOH) of chromosome 9p21 was studied using two polymorphic markers in 79 head and neck squamous cell carcinomas. 15 out of 67 (22%) DNA samples obtained from cancer specimens were revealed to have LOH when at least one marker was used. Frequency of LOH was not correlated with localization of the tumor, clinical stage of the patient, tumor size and lymph node involvement. However, frequency of LOH was significantly higher in the recurrent tumors than the no-recurrent tumors. Replication error (RER) was observed in 4 cancers. These results indicate that LOH of 9p21 is a considerable prognostic factor independent of other existing facors concerning head and neck squamous cell carcinoma.

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We examined 73 Nasopharyngeal carcinoma (NPC) patients retrospectively, treated at Keio University Hospital between January 1980 and December 1994. Our series have 53 males (72.6%) and 20 females (27.4%), ranged in years of age from 16 to 81 with a mean age of 47.8. The 5-year and 10-year overall survival rates were 58.1% and 48.8% respectively. The median survival time was 57.8 months. Nine patients survived for more than 10 years and maximum time of survival was 169 months. Cervical metastases on initial presentation occured in 51 patients (69.9%). Stage III+IV group comprise 86.3% of all, so almost of NPC patients presented with advanced stage disease. The patients with WHO type III seemed to have better survival rates than the patients with other histological types. Patient sex and age were significantly related to survival. Patients presenting with stage IV disease obviously had a poorer prognosis. The nodal (N) categories appeared to have stronger relationship to the prognosis than T categories. Neoadjuvant chemotherapy (NAC) was given to 32 patients. The response rate to NAC was 68.8% without significant toxic effects. Unfortunately NAC followed with radiotherapy resulted in no significant improvement for the survival rates. Further clinical investigation about the efficacy of adjuvant chemotherapy after radiotherapy or simultaneous chemoradiotherapy seemed to be important.

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Eighty-seven patients with squamous cell carcinoma of the lower gingiva were treated radically at Second Department of Oral and Maxillofacial Surgery, Osaka Dental University, for 17 years from 1978 to 1994. Twelve cases that died within 5 years caused by primary recurrence and/or metastasis were analyzed.
Out of them, eight cases were in the primary recurrence, one in the primary recurrence and metastatic cervical lymph node, two in the primary recurrence and metastatic lung lesion, and one in the metastatic lung lesion alone.
Though the relation of radiographic bone destruction and poor prognosis was not evident, ten cases showed T3 and T4, or high grade of histological malignancy.
The recurrent site of cases treated by mandiblectomy was not bone, but surrounding soft tissues with the posterior portion of the resected soft tissues in 5 cases, buccal portion in 4 cases and anterior portion in 1 case.
Therefore careful excision with precise safety margin must be performed in the cases of the tumor extending to the posterior or buccal side out of the mandible.

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The treatment of squamous cell carcinoma of the mesopharynx still remains controversial. Recommendations for the initial therapeutic approach to this tumor include surgery, radiation therapy or various combination therapies.
Sixty-two patients with squamous cell carcinoma of the mesopharynx treated at our hospital from 1985 through 1996 were reviewed and the treatment results of 52 recent cases were analysed. The primary lesion was located in the lateral wall in 30, the anterior wall in 14, the superior wall in 4 and the posterior wall in 4 cases. The overall five-year crude survival rate was 45%. The rate of advanced stage (stage III·IV) was 80.8%. The 5-year survival rate did not differ between patients with irradiation therapy and those with surgical treatment. In stage III and IV, the 5 year survival rate of T1·T2 cases was 90.9% and that of T3·T4 cases was 31.6%. Multiple primary cancers were discovered in 11 out of 52 patients (21.2%) with previously untreated squamous cell carcinoma of the mesopharynx.
Analysis of these series supports the recommendation that early detection of other existing cancers by physical examination, CT, MRI, ultrasonography and endoscopy of the upper aerodigestive tract and stomach is very important and selection of the optimal treatment modalities according to the location and expanse of cancers in T3 and T4 cases should be investigated.

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We investigated the presence of the lymph node metastasis in the upper mediastinum in 7 cases of the hypopharyngeal carcinomas extended to cervical esophagus and in 10 cases of cervical esophageal carinomas. In most cases of the hypopharyngeal carcinomas, we observed the metastasis to the lymph noodes in the jugular chain and in the paratracheal region, but not in the upper mediastinum, indicating that the upper mediastinal dissection is not necessary. On the other hand, 4 of 6 cases of cervical esophageal carcinomas showed the metastasis to the lymph noded in the upper mediastinum. The metastasis to this region was found when the tumor invades into adventitia of esophagus, suggesting that the depth of invasion may affect the incidence of metastasis to this region. From these results, we recommend to detect metastasis to the lymph nodes in the upper mediastinuum for the treatment of cervical esophageal carcinomas. Careful mediastinal dissection is required when the involvement of lymph node metastasis in this region is suggested.

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Sixty four cases of oral squamous cancers were examined histologically for the presence of apoptotic cells using nick end-labeling method. Apoptosis was evaluated with the apoptotic labeling index (AI) and the distribution pattern of the apoptotic cells. Mean AT value was the highest in well differentiated cancers. Cancers with focally localized apoptotic cells only in cancer pearl were less metastatic. It was suggested that apoptosis might be related to differentiation and less malignant potential of cancer.

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To compare the efficacy and toxicity of CDDP-5-FU chemothetpy (CF) and CDDP-peplomycin chemotherapy (CP) for head and neck squamous cell carcinoma, retrospective statistical analysis was done. For regimen CF, CDDP was administered 70mg/m² at day 1 and 5-FU was administered 700mg/m²/day at day 1-5. For regimen CP, CDDP was administered 50mg/m² at day 1 and peplomycin was administered 5mg/body/day at day 2-6.
Of 153 cases applied to either CF or CP from April, 1981 to December, 1995, 139 cases were evaluable for response and toxicity. In 54 cases applied to CF the response rate was 72.2% (CR 12 and PR 27), while in the 85 cases applied to CP it was 68.2% (CR 22 and PR 36). According to each primary site, in oropharynx, the response rate with CP (88.9%) was higher than with CF (72.7%). Contrary in oral cavity, the response rate with CF (66.7%) was higher than with CP (54.5%). However, there were no significant differences statistically between CF and CP. The incidences of nausea and vomiting, leukopenia and thrombocytopenia were significantly higher with CF than with CP (p<0.01). However, the above toxicities were clinically mild and transient.
To increase the response rate of these combination chemotherapy, it is necessary to establish the method to select the optimal drugs based on each sensitivity for individual patient.

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Fibronectin was examined for its possible nature as a immunotherapy of cancer. Combined with the known biological response modifier, OK-432, fibronectin was administered locally near the shotted VX2 tongue cancer in rabbits. Fibronectin enhanced the cancer-suppressing effect of OK-432, and the rate of the tumor growth suppression observed was about two-fold that observed for the not fibronectin. The extent of the cancer-suppressing efficacy of fibronectin was positively proportional of the two times (P<0.05). Also, fibronectin in combination with OK-432 significantly suppressed the metastasis to the lymph nodes as compared with the control (P<0.025). These results suggested that fibronectin may be a potentially useful immunotherapy of cancer.

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This article presents long-term treatment results by analyzing 54 skull base surgeries for the nasal-paranasal sinus malignancies treated from January 1987 to August 1996 at the Shizuoka Red Cross Hospital and the associated hospitals. Analysis was performed using a computer program, which revealed cumulative survival curves with the Kaplan-Meier method and the statistical significances of the relationships between the cumurative survival rate, local control rate, and clinical parameters such as age and sex of the patient, location and histological types of the tumor, and the complete resectability, tested by the logrank (Mantel-Cox) method.
Cumulative 5 year survival rates were 52% and 45% for all of the histological types and the squamous cell carcinoma respectively in no relation to the site of the skull base resection, and were also 69%, 36%, and 83% in the anterior, anterior-middle and middle skull base resections respectively for all of the histological types, and samely were 56%, 32% and 100% respectively for the squamous cell carcinoma. The local control rate in the completely resected cases was 70% cumulatively at postoperative 5 and 9 years for all of the histological types.
Statistical analysis revealed that such factors were estimated as prognostic ones that were;
1. age of the patient (over 70 years of age) and complete resectability of the tumor were common factors in no relation to resection sites and tumor locations on the skull base.
2. tumor locations such as orbital apex and intradural tissues in the anterior skull base resection both for all of the histological types and the squamous cell carcinoma,
3. tumor locations such as orbital apex, oval foramen, clivus and dura mater, and occurrence of the postoperative major complications in the anterior-middle skull base resection for all of the histological types, and,
4. tumor locations such as clivus and dura mater, and occurrence of the postoperative major complications in the above-mentioned resection area for the squamous cell carcinoma (10% significance level).
They were thought clinically as the high risk location in the skull base surgery for nasal-paranasal sinus malignancies which invade such regions as orbital apex, body of the sphenoid bone, more posterior portions than the oval foramen, dura mater and intradural tissues.

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The correlation between clinico-pathological malignancy grading and ultrasonographic evaluation of cervical lymph nodes metastasis was studied in 46 patients (64 lymph nodes) with oral squamous cell carcinoma from 1987 to 1996.
The following conclusions were reached, as to the ultrasonographic findings, most lymph nodes with a minimal axial diameter of 10mm or more were diagnosed as metastasis. Furthermore, most metastatic cervical lymph nodes with a minimal axial diameter of less than 10mm showed high grade malignancy of primary (≥12 points).
The present results revealed that 92.2% of the involved lymph nodes were accurately estimated by using both ultrasonography and clinico-pathological malignancy grading.
So far as lymph nodes metastasis, a combination of urtrasonography and clinico-pathological malignancy grading is thought to be useful for the detection of cervical lymph node metastasis in oral malignant tumors.

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10 cases of chemotherapy death during recent 13 years in the Otorhinolaryngologic Department of Nihon University Itabashi Hospital were reviewed. They comprised 3.9% of all admission deaths during the same period in this Department. All cases, except one, died due to bone marrow depression following chemotherapy. One case died from pulmonary fibrosis caused by peplomycin. All cases were over the age of 60, except for 2 child cases with rhabdomyosarcoma, who has received massive chemotherapy, and 2 cases, aged 43 and 51, with recurrent tumors, who had history of chemotherapy and has undergone surgery just prior to the last chemotherapy. In most cases, risk factor-renal dysfunction, pulmonary metastases, elevated transaminase, and/or concurrent radiotherapy, and/or a history of chemotherapy was present. In myelosuppression cases, nadir appeared within 8 days of completion of the last chemotherapy. Except for 2 cases, the nadir white blood cell count were all 300/μl or less and the platelet count were 2.2×10⁴/μl or less. 7 of 9 cases died within 8 days of the appearance of nadir.

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We compared the finding of preoperative high resolution CT of 11 cases of carcinoma of the external auditory canal and middle ear with postoperative pathologic findings of the involvement area.
In 4 cases the histopathological findings of surgical specimens were compatible with the preoperative HRCT. In 3 cases tumor was limited in the external auditory canal without chronic otitis media, one advance case had chronic otitis media.
It was concluded that the preoperative determination of the extent of spread of tumor must be made by accurate pathological findings by the exploratory tympanotomy, especial in casca with chronic otitis media.

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This study investigated masticatory function of postoperative oral cancer patients subjectively and objectively to obtain some suggestions for higher functional level in overall postoperative cancer patients. The subjects were 53 postoperative oral cancer patients, 23 male and 30 female, 41 to 85 years, averaged 63.1. Their masticatory function was evaluated subjectively with the Yamamoto's masticatory grade and objectively with Occlusal Prescale (Fuji Film Co.) and the low adhesive color developing chewing gum method. They were also asked with the questionnaire whether they were satisfied with their functional level and desired further rehabilitative treatment. Their functional level were ranged widely from that of normal subject to almost hard to masticate. Some patients did not want to undergo further rehabilitative managements although they had very poor functional level and/or were not sastisf ied with their functional states. Combined with the improvements of surgical and prosthetical techniques, further efforts to motivate them are also important for rehabilitation of overall postoperative oral cancer patients.

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In an attempt to evaluate properly the results of treatment for laryngeal cancer, relative survival rates by the life table method, crude cumulative survival rates and cause-specific cumulative survival rates by Kaplan-Meier method were compaired on a total of 950 patients with previously untreated laryngeal cancer in our department between 1979 and 1991.
It is suggested that both cumulative survival rates had better be shown, if not relative survival rate, in order to evaluate properly the results of treatment for laryngeal cancer, for the reasons as follows:
1) Crude cumulative survival rate alone did not show the proper result of treatment but the expected survival rate of general population, in case of truely curable cases such as glottic stage I, of which relative survival rate was nearly equal to 100%. 2) Cause-specific cumulative survival rate alone did not show the proper result of treatment, in case that may contain many cases died of intercurrent diseases such as supraglottic stage I, of which cause-specific cumulative survival rate was 100% but relative survival rate and crude cumulative survival rate were 62% and 60%, respectively. 3) The mortality rate of intercurrent diseases may be useful for comparing with other data, which was shown the difference between the two cumulative survival rates.

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In mandibular reconstruction, the iliac crest provides a sufficient amount of bone graft matreial. Vascularized iliac graft showed little bone resorption and a high viability rate even in primary reconstruction and allowed application of the prosthetic restoration early after surgery. In this study, we review cases in which vascularized iliac crest grafts were used with implants to evaluate whether implants are useful for improving the oral function as comparing with the conventional prosthetic restoration, and whether the vascularized iliac crest provides sufficient support to the implants.
12 patients were performed implant-anchored prosthesis, and 38 Bronemark Mark II, 8Bronemark standard, 7 ITI Bonefit and 2 ITI Hollowscrew implants were inserted via intra oral approach. One of the implants failed to osseointegration initially, and 1 implant was removed, because marked inflammation and bone resorption were observed around it. For implants in three patients were made sleeping implants, because their position were inadequate. After treatment with the implant-anchored prosthesis, masticatory function was improved rather than wearing conventional dentures, but speech function was not improved.

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This is a report of a multi-institutional study of 23 patients with osteosarcoma of the jaw who had surgery. The ages of the 10 males and 13 females ranged from 11 to 68 years (mean, 40.0 years). Most of the tumors of the maxilla (six cases) occurred in the posterior ridge (4 cases). In the mandible (17 cases), the posterior body was preferred site (14 cases). Swelling with hypoparesthesia was the most frequent symptom. Radiographically, most of the lesions were osteoblastic, but 3 cases were well-circumscribed osteolytic. Treatment included surgry alone (11 cases), surgery with chemotherapy (5 cases), surgery with radiotherapy (3 cases) and surgery with chemotherapy and radiotherapy (4 cases). The overall five-year and ten-year survival rate was 45.2% and 33.9%.

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Osteoradionecrosis (ORN) generally follows radiotherapy for tongue cancer, and ORN is the most serious clinical problem among these complications. In this study, we focused on the incidence of ORN of the mandible and its relationship with preradiation dental extraction. During the period 1975 through 1990, 124 previously untreated patients with histologically verified squamous cell carcinoma of the tongue were treated by brachytherapy alone or in combination with external radiotherapy. All patients were diagnosed as T1N0, T2N0, according to the TNM classification of UICC, 1979.
Twenty-one (18.4%) of 114 tongue cancer patients who underwent radiotherapy without a spacer developed ORN. Nine (20.9%) of 43 and 12 of 71 (16.9%) Patients who did and did not undergo preradiation, respectively, developed ORN. The intervals between extraction and radiotherapy for the patients who did and did not develop ORN were 6.9 and 12.4 days, respectively, indicating that at least two weeks should be allowed to elapse after extraction before starting radiotherapy. The patients who underwent preradiation extraction tended to develop ORN earlier than those who did not, and the short interval berween extraction and radiotherapy in our institute indicates that an inadequate healing time may increase the risk of ORN in the early postradiotherapy stage. We have used radiation prostheses for 10 patients since 1985, but in this study, their treatment effect was not clear although other workers have already established their usefulness.

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We treated two patients with infantile fibromatosis. The first case is a one-year and four-month-old girl who had presented with a history of the increasing painless mass in the right maxilla. The mass was surgically removed, but local recurrence occutred in six months. The second operation was carried out and the postoperative course was uneventful, with no recurrence sixteen months later.
The second one is a eight-month-old girl who had presented with a history of the right lateral cervical mass. Local excision was performd to resect the mass and it has not recurred in fifteen months after surgery.

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