Radical surgical excision is regarded as the treatment of choice for sinonasal malignant tumor. Advances in endoscopes, image technology, and powered instruments have enabled sinonasal lesions to be treated safely. Resection can be performed endoscopically for sinonasal benign tumor in selected cases. We treated endoscopically several cases of sinonasal malignant tumor which were located in the nasal cavity and the ethmoid sinus, and in more extensive cases we used an endoscope for the surgical procedure in the deep and narrow part of the sinonasal cavity. From our experiences, an endoscope is useful for the treatment of sinonasal malignant tumor in the following cases: 1) limited lesion in the nasal cavity with no invasion of adjacent structures, and 2) in surgical procedures for narrow and deep sinonasal lesions. Although an endoscope is useful for the treatment of sinonasal lesions, we should consider this method as one among several surgical options.

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Sixty-four patients with malignant maxillary sinus tumor admitted to Mi yagi Cancer Center from 1993 through 2001 were reviewed. Squamous cell carcinoma was the most common tumor (81%). The overall 5-year survival rate of all patients was 45%. The 5-year survival rates were 48% in untreated patients and 29% in treated patients. The 5-year survival rates were 50% in untreated patients with no lymph node metastasis and 16% in untreated patients with lymph node metastasis. Previous treatment, treatment modality and N classification were statistically related to the outcome.

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We reviewed the records of 45 patients with squamous cell carcinoma of maxillary sinus who underwent radiotherapy and intra-arterial chemotherapy with or without maxillectomy. Of 45 patients, 10 patients (stage II:III:IVA=1:5:4) were operated with radical radiotherapy without maxillectomy and had no local failure for more than 1 year (conservative and no local failure group), and 9 patients (stage III:IVA=3:6) were performed with partial or total maxillectomy after pre-operative radiotherapy and had no malignant cells in the operated specimen (group B). Complete response on radiological images was shown in 70% of patients in group A, and 67% of patients in group B. In group A, local recurrence was found in 1 of 10 patients in group A and 1 of 9 patients in group B during a further follow-up period. Five-year overall survival rate was 53% and 67% in group A and B, respectively. Five-year cause-specific survival rate was 89% and 67% in group A and B, respectively. Maxillary conservative treatment is appropriate in cases showing good response on radiological images after radiotherapy combined with concurrent intra-arterial infusion chemotherapy.

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Heparanase is an enzyme specifically degrading heparan sulfate in the basement membrane and is thought to play a role in cancer invasion. It has been shown that heparanase is involved in the process of metastasis in many malignant tumors.
In this study, we examined the correlation between heparanase mRNA expression and lymph node metastasis in oral squamous cell carcinoma. Specimens were obtained from 25 patients by biopsies or operations performed in our clinic from 1997 to 2000. Quantitative PCR was done for measurement of heparanase mRNA expression levels.
Five of 11 patients, operated with neck dissection and excision of primary lesions, had pathologically proven lymph node metastasis: 3 showed a high level of expression of heparanase mRNA and 1 showed moderate expression. Six patients subsequently developed lymph node metastasis: 1 showed a high level of expression, 3 cases a moderate level and 2 a low level of expression.
Statistical analysis indicated that heparanase mRNA expression and lymph node metastasis in oral squamous cell carcinoma were significantly correlated and suggested that heparanase may be a useful marker for the diagnosis of lymph node metastasis.

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In order to improve the prognosis of oral cancer patients, it is important to perform initial therapy with consideration of the cancer character of each patient.
We have used a histological malignancy grading system for planning the therapeutic modality of oral squamous cell carcinoma (SCC) patients since 1992. In this paper, we discuss whether the grading system has a prognostic value for recurrence and metastasis or not, and whether this system will contribute to improve the prognosis.
Two hundred and fifteen oral SCC patients were examined to investigate the relationship between malignancy grading and prognosis retrospectively. The results suggested that malignancy grading was closely related to recurrence, metastasis and survival. We consider that sufficient surgical margin, elective neck dissection and close observation after initial therapy are necessary for patients with high malignancy grade tumor. We used these policies for the planning and treatment of 227 patients from 1992 and verified that effect on prognosis.
In the patients with high malignancy grade tumor, the incidence of recurrence and secondary metastasis decreased from 30.8% to 13.5% (p<0.01), and from 35.4% to 26.1% (ns), respectively. The 5-year survival rate improved from 53.9% to 73.8% (p<0.05).
These data suggested that histological malignancy grading was a good prognostic factor. We should use the malignancy grading system to select high-risk patients and appropriate therapy for them.

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Malignant tumors of the head and neck involve the mandible by direct invasion from soft tissues into the cortical bone and the bone marrow accompanying bone destruction and by intramedullary invasion along the mandibular canal. In clinical pathology, the pattern of bone infiltration of malignant tumors is classified into the osteolytic type, osteoplastic type, and intertrabecular type. For determination of the area of mandibulectomy, imaging studies of the tumor by high-resolution MRI are needed. But this determination is difficult depending on the presence or absence of intramedullary metastasis or dissemination, or when the tumor has become fibrous due to radiation therapy in the past. We studied the pattern of cortical and medullary invasion histopathologically in 18 patients who underwent mandibulectomy with malignant tumors of the head and neck region in whom preoperative imaging diagnoses could be compared with pathological findings. All 16 patients with squamous cell carcinoma showed osteolytic type which was continuous in the mandibular marrow without intramedullary metastasis. Since squamous cell carcinoma invading into the mandible shows continuous and direct bone invasion, the clinical management of mandibulectomy may be determined with high-resolution MRI.

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This paper presents the results of radical radiotherapy and salvage surgery in patients with carcinoma of the larynx or hypopharynx.
Between 1986 and 2002, 120 patients with carcinoma of the larynx or hypopharynx were treated with radical radiotherapy (Stage III in 25 patients and Stage N in 95 patients, laryngeal cancer in 50 patients and hypopharyngeal cancer in 70 patients). Eighty-nine patients were treated with radiotherapy alone, and 31 patients were treated with concurrent chemo-radiotherapy with cisplatin and 5-fluorouracil (CF) chemotherapy.
The locoregional control rates of stage III patients (72%) were better than those of stage IV patients (44%), but there was no difference between patients with laryngeal carcinoma (34%) and those with hypopharyngeal carcinoma (47%).
Salvage surgery should be applied only to selected cases for whom resection is deemed likely to result in good locoregional control and QOL, and to reduce surgical complications.
Although the usefulness of concurrent chemoradiotherapy for advanced hypopharyngeal carcinoma was suggested, salvage surgery was unsuccessful in one case after concurrent chemoradiotherapy because of delay of wound healing.
In conclusion, radical radiotherapy is applied to stage i patients with not only laryngeal carcinoma but also hypopharyngeal carcinoma. Salvage surgery is recommended only for those cases confirmed to be resectable.

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It is accepted that carcinoma of the hypopharynx has a tendency to metastasize to the neck lymph nodes. In addition, a common fatal prognostic factor is metastasis to the lateral retropharyngeal nodes (Rouviere's lymph nodes). In this study, we reviewed retrospectively metastases to lateral retropharyngeal nodes in 214 hypopharyngeal cancer patients who were treated in Kurume University Hospital and analyzed the prognostic factors.
Metastases to Rouviere's lymph nodes were found in 21 (10%) of 214 patients (stage I: 0%, II: 3%, III: 10%, IV: 12%).
The cause-specific five-year survival rate determined using the Kaplan-Meier method was 69% for patients with negative Rouviere's lymph nodes and 41% for patients with positive Rouviere's lymph nodes. There was a statistically significant difference between the two survival rates (p<5%).
Fourteen (19%) of 76 patients who underwent retropharyngeal lymph nodes dissection had pathologically positive nodes. Distant metastasis was detected in 8 (13%) of the 62 patients whose retropharyngeal lymph nodes were pathologically negative. On the contrary, 6 (43%) of the 14 patients whose retropharyngeal nodes were pathologically positive had distant metastases. There was a statistically significant difference in the rate of distant metastases (p<1%) between them.
Eleven patients whose retropharyngeal lymph nodes at neck dissection were pathologically positive and received additional radiotherapy did not show recurrence in the Rouviere's lymph nodes.
These results highly support the efficacy of retropharyngeal lymph nodes dissection and postoperative irradiation for the Rouviere's lymph nodes in hypopharyngeal carcinomas.

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We isolated a metastasizing human esophageal squamous cell carcinoma cell line, T.Tn-AT1 from a parental non-metastasizing cell line, T.Tn. Firstly, T.Tn-AT1 was isolated by in vitro selection, in which the cells with high cell-substrate and cell-cell adhesion were obtained. Subsequently, their metastasizing potential in vivo was confirmed by a nude mouse orthotopic inoculation model. We compared the expression profile of 9, 206 genes between T.Tn-AT1 and T.Tn by microarray analysis. The gene expression profiles of T.Tn and T.Tn-AT1 were very similar, and only 114 genes showed more than two fold differential expression. In the 114 genes, 86 genes were down-regulated in T.Tn-AT1 cells, and only 28 genes were up-regulated in T.Tn-AT1 cells. Most of the identified genes encoded the proteins associated with metastatic processes, such as adhesion, migration, inflammation, proliferation, and differentiation.

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Seventy-four patients with untreated cervical esophageal carcinoma underwent resection of primary lesion from 1982 to 2000 in our hospital. We reviewed the clinical data on these 74 patients. The 5-year overall survival rate by pathological stage was 75.0% in Stage I, 43.3% in Stage II, 11.7% in Stage III, 5.8% in Stage IV, and 23.9% in all stages. The 5-year local control rate was 87.8% and the regional lymph node metastasis rate was 36.5%. These results indicated that cervical esophageal carcinoma is a highly lethal cancer among head and neck cancers.
Surgical treatment of cervical esophageal carcinoma is influenced by special problems arising from the anatomical characteristics of this organ. We must consider the patient's quality of life in treating high lethal cancers such as cervical esophageal carcinoma. In our hospital we positively tried to preserve the larynx. Twenty-one of 74 patients were selected for resection of the cervical esophagus preserving the larynx. Local recurrence occurred in 3 cases in the preserving-larynx group and 4 cases in the not-preserving-larynx group. There was no significant difference statistically between the two groups. These results indicated that resection of the cervical esophagus preserving the larynx should be positively selected.

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Recently, the incidence of multiple primary cancer in head and neck cancer patients is increasing. Among 337 cases with head and neck cancers treated at Tokai University Hospital from January 1995 to December 2000, 76 cases (22.8%) had multiple cancers. About 85% of multiple primary cancers were found in the upper aerodigestive tract including esophagus and stomach. Simultaneous esophageal cancer was detected in 27 cases (8.0%). Multiple primary cancers of head and neck at our hospital from 1982 to 1992 were reported previously, in which simultaneous esophageal cancers were found with similar incidence to this study. The importance of systematic screening of esophageal cancer with endoscpic examination was emphasized.

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The recurrent laryngeal nerve may need to be sacrificed because of invasion by thyroid cancer. Although unilateral resection of the nerve is not so fatal, the patient's suffering is serious. Traditionally, reconstruction of the recurrent laryngeal nerve has been considered unnecessary, because the procedure cannot restore normal movement. The patient's phonation improves, however, bacause the reconstructed cords recover from atrophy and restore tension during phonation. Immediate reconstruction of the recurrent laryngeal nerve was performed for 13 patients whose nerves were resected. Free nerve grafting in 5, and ansa cervicalis to recurrent laryngeal nerve anastomosis in 8 patients were conducted. Mobility was not observed in all 13 patients. The maximum phonation time (MPT) was regained within the normal range in 9 patients, and phonation quotient (VC/MPT) was improved within the normal range in 11 patients. On the other hand, improvement of MPT and VC/MPT was not obtained in 6 patients whose resected recurrent laryngeal nerve was not reconstructed.

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Although distant metastasis (M) represents the most important prognostic factor for cancer-specific death of patients with papillary thyroid carcinoma (PTC), some patients display extremely slow-growing M. Correctly predicting prognosis is extremely difficult in such cases.
Of 604 patients with PTC at our institution (1976-1998, excluding microcarcinoma), 32 patients (5.3%) displayed M at presentation and 26 patients (4.3%) developed M after primary surgery. Of the 58 total patients with M, 28 (48.3%) died of the disease. Of these, 5 died from local invasion of PTC or complications associated with treatment. Conversely, 7 patients with M displayed complete response to radio-iodine therapy and/or resection of metastatic lesions.
Patients displaying rapid progression of M (n=24) were compared with patients (n=24) in whom M demonstrated no change over 5-year observation. Age (<50 years old), smaller M (<2-cm diameter), lung metastasis without other M, and primary tumor predominantly comprising well-differentiated components were associated with significantly improved survival.
In conclusion, local control of PTC is significant even in patients with M, particularly when M appears to be slow-growing.

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We have performed dynamic supplemental reconstruction by transferring the temporal muscle to raise the base of the reconstructed tongue or reconstructive soft palates since 1992. The temporal muscle flap was elevated and transferred to the area under the zygomatic arch to lift the reconstructed tongue by the same method as in dynamic reconstruction after facial paralysis. In total glossectomy, bilateral temporal muscle flaps were elevated to raise the reconstructed musculocutaneous flap. The temporal muscle is innervated from the third branch of the trigeminal nerve and can coordinate with the peri-pharynx muscles in swallowing.
We have done video analysis of deglutition and articulation. The temporal muscle suspension transfers the force of the remaining pharyngeal muscles to the reconstructed tongue and the reconstructed soft palate because the temporal muscles simultaneously shrink with the surrounding pharyngeal muscles.
In total tongue reconstruction cases, the articulation was done between the lifted reconstructive tongue and the soft palate.
Our patients with a total glossectomy could talk to their family and friends over the telephone.

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Adequate tissue transfer is required to obtain good results of oral functions in patients with reconstruction after hemiglossectomy, particularly half resection of the movable portion of the tongue. In this paper we describe evaluations of postoperative oral functions in patients with reconstruction using a free rectus abdominis musculocutaneous flap or a radial forearm flap. Speech intelligibility, swallowing disorder, and the volume of transferred tissue were studied in 16 patients: 8 patients with a free rectus abdominis musclocutaneous flap (rectus group) and 8 with a forearm flap (forearm group). Regarding speech intelligibility and swallowing disorder, there were no remarkable problems in activities of daily life in all the patients and differences between the rectus and forearm group. In CT scanning images, the pharyngeal space had a tendency to be narrow in the rectus group, and to be wide in the forearm group.
From the results obtained we may choose a free rectus abdominis musculocutaneous flap for a slender patient and a forearm flap for an obese patient.

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It is recognized as standard surgery to perform immediate reconstruction using free flap after excision of head and neck tumors. In this paper, we discuss the postoperative functions of swallowing and articulation after major glossectomy. Persistent aspiration developed in one patient who underwent total glossectomy. When laryngoplasty was done, the patient underwent secondary total laryngectomy. Other patients in whom a little root of the tongue was preserved were able to eat orally. The function of articulation was poor in patients with total and near-total glossectomy as well as in patients with resection of the oral floor.

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This study reconsidered the principle of reconstruction following hemiglossectomy of limited mobile tongue. A radial forearm flap was the first choice except for young women and patients with severe disease. A rectus abdominis flap was selected for young women to consider the donor site. On the other hand, a pectoralis major myocutaneous flap was selected for patients who needed a shorter operating time, in order to reduce the risk with severe disease. Regardless of which flap was selected, it was very important for the postoperative oral function to raise a flap sufficiently larger than the size of the defect.
Between 1979 and 2002, a total of 50 patients underwent reconstruction, with 38 radial forearm flaps, 4 rectus abdominis flaps, and 8 pectralis major myocutaneous flaps following hemiglossectomy of limited mobile tongue. Each case was assessed regarding postoperative function.
The data for the radial forearm flaps showed the best results postoperatively, with the most flexible movement of the residual tongue. On the other hand, the results for the pectralis major myocutaneous flap group showed the least flexibility of movement of the residual tongue. In addition, the flaps were too bulky in comparison to the forearm flaps and showed scarring at 3 months postoperatively. However, due to the need to reduce the risk with severe conditions, operating time was the shortest among them. Concerning wound of the donor site, a rectus abdominis flap was more inconspicuous compared with the radial forearm flap. Although this type of flap was considered bulky, by reducting the flap volume it was possible to improve the postoperative function to the same level as that of the forearm flap.

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A study of TS-1, a novel oral antitumor agent of fluorinated pyrimidines, in patients with recurrent head and neck cancer was conducted in 23 patients. Objective response was 1 complete response, for a response rate of 30.4%. Grade 4 thrombocytopenia and pneumonia were observed in one case; however, this returned to the normal level after the termination of drug administration and blood transfusion and steroid. There fore, this event was confirmed to be reversible. For patients with lung metastasis, median survival time was 585 days in the TS-1 group (n=6), and, 120 days in the conventional therapy group without TS-1 (n=6). The TS-1 method was useful from the point of view of QOL. Based on these results, we believe that TS-1 is an active agent for the treatment of recurrent or lung metastastic head and neck cancer.

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Patients with recurrent and/or metastatic head and neck cancer are often primarily treated with surgical resection and/or radiation therapy and/or chemotherapy, in which case the secondary therapy options are limited. Consequently, based on tumor dormancy therapy, we performed weekly docetaxel therapy for 36 outpatients with recurrent and/or metastatic head and neck cancer since June 2000, and evaluated the efficacy and toxicity. In this study, docetaxel was administered by 1 hour intravenous infusion at a dose of 20 or 30mg/body every week. Administration was continued for 3 weeks followed by 1 week of rest. The short course premedication schedule consisted of 8mg dexamethasone for 30 minutes prior to docetaxel. Results of patient response evaluation were 4 CR, 4 PR, 17 NC, and 11 PD. The overall response rate was 22.2% and a better than NC response was seen in 69.4%. In terms of tumor dormancy therapy, this is an excellent and effective treatment for such patients. Toxicities observed were mostly mild, with only 1 patient having Grade 3 liver function damage. We consider that this therapy can be safely used for outpatients.

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