Concurrent chemoradiotherapy were performed for 18 patients with unresectable head and neck squamous cell cancer. Chemotherapy, consisting of CDDP (40mg/m², Day 1 and 8) and 5-FU (200mg/m², 24-h continuous Infusion through Day 1-5 and 8-12), with concurrent radiotherapy (2Gy/day, 5 days/w) were administered and repeated 2-3 courses in every 5 weeks. Mucositis and myelo-suppression were the main side effects observed, but all of them were tolerable. Total response rate and complete response rate was 94.4% and 55.6%, respectively. Out of six patients requiring tracheotomy for airway obstruction due to bulky tumor, four achieved sufficient tumor shrinkage by the treatment and could obtain closure of the stoma. Two patients whose neck lymph nodes were still remaining after chemoradiotherapy, could obtain local control by supplemental neck dissection surgery. These ragimen is feasible and effective for locally advanced head and neck cancer.

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The treatment of laryngeal cancer is selected in consideration of a tumor site, TN staging, growth pattern of the tumor and the others, resulting in the relatively good 5-year-survivals in comparison with other cancers.
However, the prognosis of the patients with advanced supraglottic cancer and/or metastasis to the neck lymph nodes has been poor.
The 192 cases of laryngeal cancer were treated at our institution between September 1986 and December 1996. Seven cases of N2c at the time of therapy and 5 cases of pT4pN2c by bilateral neck dissections were reviewed. Those 12 cases were classified in supraglottic cancer, including one case with multicentric lesions. Radiation therapy was carried out in two cases (T1 and T2), one of which needed neck dissection later. Total laryngectomy with bilateral neck dissections were performed in other cases. Postoperative irradiation was carried out in 4 of 5 cases of pT4pN2c. Those cases resulted in no evidence of disease (6 cases), death of distant metastasis (5 cases) and death of another cancer (1 case) without local and neck recurrence.
Prophylactic neck dissection is important except for T1, some of T2 cases. It is stressed that bilateral thorough neck dissection for T4 supraglottic cancer cases and postoperative irradiation for pN2c case are effective. A strategy to distant metastasis is the theme to improve the cure rate of T4N2c cases.

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It has been reported that vessel density correlates with the intensity of VEGF expression and metastasis in breast cancer, colon cancer and prostate cancer, suggesting that vessel density is a prognostic factor. However, controversial data exist regarding the predictability of lymph node metastasis or prognosis based on vessel density in head and neck squamous cell carcinoma (HNSCC). To assess the clinical significance of angiogenesis in HNSCC, we examined vessel density immunohistochemically in 44 primary oral squamous cell carcinomas (SCCs) using 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. There was no association of vessel density with tumor site, T-category, degree of differentiation or cervical lymph node metastasis, except that the vessel density of carcinomas with a well-defined tumor-stromal boundary was higher than that of diffusely invasive carcinomas. The intensity of VEGF expression correlated with lymph node metastasis and expression of Flt-4 most significantly correlated with lymph node metastasis. These results suggest that not only angiogenesis but also lymphatic vessel neogenesis should be further examined in predicting metastasis and establishing prognosis in HNSCC.

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Ten patients with unresectable head and neck cancers and nine for neoajuvant chemotherapy were treated by two-route intra-arterial chemotherapy using cis-diamminedichloroplatinum (CDDP) and sodium thiosulfate (STS). In these patients, 100mg/m² of CDDP was administered weekly through each feeding artery of the tumor superselectively at 5mg/mm. During infusion of CDDP, STS of one-hundred fold of CDDP was injected through catheter placed in the brachiocephic vein introduced via the subclavian vein. The complete and partial response rates were 14/19 (74%) and 5/19 (26%), respectively. None of the nine patients following operation showed histlogically residual tumor. Three of the recurrent 4 cases showed partial response, which could have been attributed to the incapability to conduct superselective infusion. All the patients were free from chemotoxicity such as renal, hematological dysfunctions, or gastrointestinal symptoms. Each chemotherapy could be done weekly on schedule, and the treatment period between 1st intra-arterial infusion and surgery was only 21±1.5 days and its period was much shortened. This new method of chemotherapy seems very efficient for advanced head and neck cancers.

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Three cell lines, IMC-2, IMC-3 and IMC-4 established from a patient with maxillary squamous cell carcinoma were used to determine the relationship between epidermal growth factor receptor (EGFR) and radiosensitivity. Immunostaining was performed with an anti-EGFR antibody. The intensity of staining reactivity was determined using an image analysis system and expressed as grey value (0-black to 255-white). The mean grey values of IMC-2, IMC-3 and IMC-4 were 181, 210 and 222, respectively, and were significantly different from one another (p<0.001). Therefore, there was the highest number of EGFR in IMC-2, secondary in IMC-3 and the lowest in IMC-4. The cells were then irradiated at 1, 2, 4, or 6Gy. Cell survival was assessed by a standard colony-forming assay. The highest surviving rates were shown in IMC-2 at 1, 2 and 4Gy, secondary in IMC-3 and the lowest in IMC-4. These results were significantly different between IMC-2 and IMC-4, and IMC-3 and IMC-4, but not significantly different between IMC-2 and IMC-3. The surviving rates of IMC-2, IMC-3 and IMC-4 after irradiation increased in the order of amount of EGFR in each cell line. The results support the findings of previous clinical studies that showed that increased expression of EGFR was associated with higher recurrence rates of glottic and maxillary sinus carcinoma in patients treated with radiation therapy. The amount of EGFR in cells may therefore be associated with their radiosensitivity.

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We investigated the difference of histological malignancy between primary lesion and recurrent lesion using malignancy grading system by Lund (Jakobsson) for oral squamous cell carcinomas. Patients were divided into radiation group (20 patients) and surgery group (10 patients). The incidence of patients whose malignancy was increased was 40% in surgery group and 75% in radiation group. The mean points of total malignancy score was increased from 18.8 to 22.0 points (p<0.05) in radiation group while from 18.4 to 18.9 points (ns) in surgery group. In eight factors of grading system, the point of “appearance”, “nuclear differentiation” and “cellular response” were significantly increased in radiation group (p<0.05), although there was no significant increase in surgery group. The characteristic changes in recurrent tumor compared with primary tumor were that all four factors for tumor-host relationship became worth in both group, especially radiation group. It was suggested that resistance of host tissue against tumors was reduced in recurrent tumor and adjacent tissue after initial therapy.

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The aim of this study is to assess the safety of a neck dissection in which the fat pad was servered in certain areas deliberately in order to be removed as divided spaces instead of a standard en bloc manner. This surgical approach was applied to three patients with head and neck squamous cell carcinoma staged N2b. The cervical fat pad was divided into three compartments separeted anteriorly by the internal jugular vein and posteriorly by the spinal accesory nerve. Each compartment was dissected free from the other ones. The fat pad thus removed, consisting of 9 separatic speciments, were serially sectioned in the direction vertical to the lymphatic flow so that the extent of tumor cell spread could be traced in the lymphatics. There were 11 lymphnodes that contained metastatic disease in the 9 specimens examined. Of the 11 positive nodes, seven showed an evidence of tumor cells in the lymphatic duct adjacent to the capsule of these nodes. However, no tumor cell infiltration was found in the lymphatic duct located far from the nodes involved with metastases. The observaation suggests that the possibility of tumor dissemination seems to be unaffected by this surgical approach that allows for division of lymph node bearing fat pad. In the presence of metastatic nodal disease, this surgical technique may be safely employed, propvided the capsule of the nodes that contain metastatic disease remains surgically intact.

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The CD40 protein on the surface of B cells has several functions: induction of isotype switching in the presence of cytokine; proliferation, association with apoptosis, et al. In this study, we investigated whether head and neck cancer cell lines have CD40 on the surface of tumor cells and what would be induced by the signal of CD40. In only HTC/C3 cell line derived from thyroid cancer, CD40 was detected by a flowcytometry among five cell lines (KB, IMC-2, IMC-3, CA-19.9). The addition of anti-CD40 Ab inhibited the colony formation by HTC/C3 cell line, but not inhibited that of other four cell lines. No cytotoxicity of CD40 signal to HTC/C3 cell line was observed by MTT assay. CD40 signal enhanced the expression of Bcl-2 in HTC/C3 cell line, suggesting the Bcl-2 is associated with slow-growth of the tumor cells by CD40 stimulation. Further study concerning the inhibition of cell growth in HTC/C3 by anti-CD40 Ab is required to clarify the role of CD40 signal.

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The problems of osseointegrated implants placed in irradiated tissues has been discussed from the review of our multicenter study and other literature. This review revealed the followings. The most suitable time interval from radiotherapy to implant surgery was 1-2 years. The risks of implant failure have to be recognized even in low dose irradiated patients. The effect of hyperbaric oxygenation was not clear for implants placed in the mandible.

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Spindle cell carcinoma composed of carcinomatous and sarcomatoid components is an unusual and aggressive variant of squamous cell carcinoma.
Four consecutive cases of spindle cell carcinoma of the tongue, which accounted for 0.9% of all tongue malignancies treated at Chiba Cancer Center Hospital were reviewed.
There were 2 male and 2 female patients, and their ages ranged from 49 to 86 years with a mean of 63.5 years. Two patients had a history of prior radiation therapy for squamous cell carcinoma of the tongue. The gross appearance was predominantly exophytic in 2 tumors, endophytic in 1 tumor, and mixed in 1 tumor. Only one patient was diagnosed with spindle cell carcinoma by biopsy specimens, however, the other 3 patients were noted to have spindle cell carcinoma in surgical specimens. When clinically suspected, biopsies should include the base and/or stalk of the tumor. Contrary to other reports the primary lesion had a small amount of sarcomatoid components, however the amount increased when recurred. Three of the patients had or developed multiple neck node metastases. The metastatic foci showed both carcinomatous and sarcomatoid components, and the amount of sarcomatoid components increased as compared with those of primary tumors.
As the initial treatment for the primary tumor, 3 patients had surgery and one patient had radiation therapy, but it recurred in 3 patients. Two of them were salvaged by a total glossectomy. Two patients were alive with no evidence of disease 55 months and 8 months, and 2 patients died of their disease within 14 months from diagnosis.
Spindle cell carcinoma of the tongue is formidable disease that requires an aggressive surgery combined with postoperative irradiation.

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To assess how to influence the four indexes of the patient's QOL status, such as sociability, psychological status, somatic discomfort and physical function, by giving information about their cancer, QOL studies (Functional Living Index-Cancer: FLIC) for 75 patients with head and neck cancer were done approximately every two weeks from admission to discharge.
Sociability (P=0.04), psychological status (P=0.003) and somatic discomfort (P=0.0001) had improved by the time of discharge.
Those patients who were informed about their cancer maintained a better QOL status of sociability (P=0.03) and psychological status (P=0.03) than did those who were not informed.
Multiple regression techniques were used to determine any factor, including the information about cancer, which correlate sociabilty and psychological status. The information about cancer (P=0.008) and surgical treatment (P=0.040) were correlated with improvement of sociability.
But only surgical treatment was correlated with psychological status (P=0.048). This result suggested that the information about cancer which might lead patients to understand the necessity of surgery, could not relieve patients from psychological distress after surgery.

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A new stage classification of nasopharyngeal carcinoma was reported from UICC in 1997. It is defined as: confined to nasopharynx; T1, oropharynx or nasal fossa; T2a, parapharynx extension; T2b, bone or paranasal sinus invasion; T3. CT or MRI examination is indispensable for new classification. N staging, is defined as: unilateral; N1, bilateral; N2, >6cm or supraclavicular fossa nodes; N3. Stage IV is restricted to cases of T4 or N3 or M1 We examined 30 patients with nasopharyngeal squamous cell carci-noma who took examinations of CT or MRI on first visit at Keio University Hospital between 1984 and 1995. A comparative study was performed between new and former classifications. For stage classification, down staging was observed in 19 cases, and up staging was observed in 1 case. Some stage IV cases were devided into stage II or III by new classification. More patients are necessary to evaluate the efficacy of new classification.

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In 1992, Numata et al. first reported contralateral external carotid-middle cerebral artery bypass grafting for head and neck cancer. With this technique, the bypass route does not interfere the operative field for the cervical cancerous lesion so that the carotid blowout following local infection is preventable. And this surgical procedure requires no shunting method so that the tumor can be removed completely with the affected carotid artery.
We used this technique for a 66-year-old man who had oral cancer with cervical metastases (T2N2bM0).
This patient had no postoperative ischemic sequelae and has survived without any signs of recurrence for 25 months. We recognized the uniqueness of this technique and also made a few inventions including the clipping of the intracranial carotid artery.

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The thigh flap and the upper arm flap have become more common as tissues for reconstruction following to tumor resection in the head and neck. Both flaps have similar quality, but differ in that the upper arm falp is thinner and more pliable than the thigh flap. The thigh flap is 1.7 times as thick as the upper arm flap. The comparative study was performed to know which was better in reconstruction following to the resection for tongue cancer. Ten patients undergoing the upper arm flap transfer (medial 5, posterior 4, lateral 1) and seven patients undergoing the thigh flap transfer (anterolateral in all) were evaluated about the articulation function, the swallowing ability and so on. The resection ranged a half of the mobile part and the root of the tongue evenly in all patients. The patients obtained good articulation function irrespective of the sort of the flap, having about 80% of 100 Japanese monosyllables being accurately heard. It was noticed that patients transferred the thigh flap had larger range of intelligibility than those of the upper arm. The incidence of dysphagia was almost same in each flap, being 30%. In conclusion, there could not be seen the difference of function between two flaps in use for the patient who underwewnt the resection of a half tongue. It is recommended that the selection of the flap should be done by the patient's preference about the donor site scar.

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Concomitant chemoradiotherapy with CDDP and 5FU given to 18 patients with nasopharyngeal carcinoma during January 1994-October 1996. One and 17 were in Stages III-IV respectively. None had distant metastasis. The median duration of follow-up of all patients was 23.5 months (6-45). Objective responce (CR+PR) of the primary lesion and the regional nodes was 18/18 (100%), whereas CR was 2/18 (11%). CR+PR and CR at the primary lesion were 18/18 (100%) and 5/18 (28%) respectively. Two patients died of disease at T site. One patient was alive with disease. The remaining 15 (83%) patients were relapse free alive. There were 2 relapses, 1 at T+M, and 1 at T+N sites. Side effects, especially myelosuppression and mucositis, were severe. Leukopnia and mucositis in grade 3-4 were 78% and 89% respectively. In conclusion, this regimen has been effective in short term follow-up. However, because of severe side effects, further modifications are required. Long term follow-up are required to difine final effectiveness of this regimen.

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We investigated 115 patients with oral cancer (76 males and 39 females) and 121 people without oral cancer (69 males and 52 females) both groups with history of tobacco and alcohol use. We drew blood from both groups and analyzed of ALDH2 genotyping. In cancer group smoking rate (male 84.2% and female 35.9%) and drinking rate (male 77.7% and female 35.9%) was significantly higher than in non cancer group (Smoking rate: male 68.1% and female 5.8%, Drinking rate: male 43.6% and female 5.8%, p<0.05). In cancer group, heavy smoker (pack-years 50+) and heavy drinker (sake index 60+) rates were significantly higher than in non cancer group (p<0.05).
The incidence of ALDH 2*2 allele in cancer group with drinking habit was 31.5% higher than in non cancer group with drinking habit (18.1%). We considered ALDH 2*2 allele possibily a new risk factor of developing oral cancer and it is very useful for screening oral cancer.

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The prognostic factors related to the long-term survival of the cases with stage IV head and neck squamous cell carcinoma were studied.
We analysed the prognostic significance of some factors in relation to long-term survival by the overall survival curve with Kaplan-Meier method in 179 patients who underwent primary treatment in our clinic from 1982 to 1992.
The primary site status (T-categories) was not affected the long-term survival, but N3, M1 and extracapsular invasion of lymph node metastases diagnosed with ultrasonography significantly related to poor prognosis.
This ultrasonographic diagnosis of extracapsular invasion of lymph node metastases was also able to affect the prognosis of N2 cases.
The group of patients treated with radical operation had the better prognosis than the group with irradiation in the cases without ultrasonographic diagnosis of extracapsular invasion of lymph node metastases. However in the cases with extracapsular invasion of lymph node metastases, the prognosis did not differ between partients with surgical treatment and those with radiation therapy.
Analysis of these series supports the recommendation that the cervical lymphnode metastases and its extracapsular invasion was very important and valuable factor related to the prognosis of the cases with stage IV head and neck squamous cell carcinoma.

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Some reports suggest that vertical partial laryngectomy (VPL) following previous irradiation is an on-cologically sound procedure with excellent local control and survival rates, however, with an increased complication rate. The purpose of this retrospective study is to evaluate the efficacy and safety of VPL for glottic carcinoma after failure of radiotherapy.
A total of 536 patients with early glottic squamous carcinomas (stage I, II) received radiation therapy between 1979 and 1994. Of 97 with locally recurrent carcinomas, VPL for salvage was performed on 35 patients (group A). In the same period, VPL was performed on 28 patients without radiation therapy (group B), and on 10 patients with previous irradiation in other hospitals (group C). The local control rates for VPL were 86% in group A, 86% in group B and 80% in group C, and the laryngeal preservation rates 80%, 86% and 80%, respectively. The 5-year survival rates were 84% in group A, 96% in group B and 90% in group C, and cause-specific survival rates 93%, 100% and 90%, respectively. The mean time of decanulation and removal of the nasogastric tube were 9 days, 12 days in group A; 8 days, 11 days in group B; and 13 days, 14 days in group C, respectively. The chondritis of the thyroid cartilage was found in 2 patients; one was cured with medical treatment in group C, the other required a total laryngectomy in group A.
Our results indicated that VPL is a useful and oncologically sound procedure for salvage of failure of radiotherapy.

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In a review of 61 patients irradiated their eye balls in the Department of Radiology, Fukuoka University, from 1973 to 1997, radiation cataract as late effect occurred in 17 patients (27.9%), in 25 eye balls (22.1%).
The periods from radiation to appear the cataract were correlated closely with total radiation dose to the lens.
The radiation cataract developed earlier on cases irradiation with large total dose than with small total dose.
According to the fraction size, the radiation cataract rates were higher in the patients irradiated over 1.5Gy than the patients irradiated under 1.5Gy, with significant difference.
Five percent radiation cataract dose after 5 year was TDF 13 (95% confidence limits 11-14), 50% dose was 21 (19-23), and 95% dose was 35 (31-39).

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Preoperative X-ray CT examination using a dental CT software program was perfomed for 9 patients with oral squamous cell carcinoma, who underwent resection of the mandible in our clinic during the period from 1995 to 1996. Histopathological findings were compared with preoperative imaging diagnosis in 9 cases postoperatively. For the patients with bone resorption of pressure type, the range and depth of resorption shown in the X-ray pictures were almost identical with those in the dental CT images. However, in the patients with bone resorption of moth-eaten type, the range shown in the dental CT images was wider than that in the X-ray pictures. When the bone resorption was found histologically to be localized on one side of the buccal or lingual alveolar ridge, the range and depth of resorption was clearly displayed by dental CT images but not observed in X-ray pictures. The range and depth of bone resorption shown in the dental CT images were consistent with the histological observations in most of the cases.
Thus, dental CT images may provide information for range of bone resorption accurately, which is very useful in determining the method of mandibular resection.

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Our previous studies have suggested that invasion into the muscular layer may be the most reliable parameter to predict subsegent lymph node metastases in squamous cell carcinomas of the tongue. In this study, the relationship between histologic features of the tumor in the muscular layer and lymph node metastasis were investigated. Ten patients with pT1N0 carcinoma developing subsequent cervical metastases and ten patients with pT1N0 carcinoma without metastases, all of which were treated with a partial glossectomy alone, were analyzed histologically in pattern of muscular invasion, differentiation and keratinazation. The incidence of nodal metastasis for tropfige infiltration and confluent invasion was 47% (8/17) and 67% (2/3), respectively. This difference was not significant. The incidence of nodal metastasis for well differentiated tumor and poorly differentiated tumor was 38% (5/13) and 83% (5/6), respectively. The incidence of nodal metastasis for tumor with cancer pearls and tumors without ones was 18% (2/11) and 89% (8/9), respectively. All of three well differentiated tumors but with no cancer pearls developed cervical metastases. Therefore, these results indicate that pattern of muscular invasion is not an unreliable indicator of nodal metastasis but assessment of differentiation and keratinization of the tumor in the muscular layer may be useful in predicting cervical nodal metastasis in squamous cell carcinoma of the tongue.

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