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We report two successful remnant and recurrent cases of head and neck cancer treated with S-1. Case 1, a 52-year-old man, was diagnosed as supraglottic laryngeal carcinoma (T3N2cM0, squamous cell carcinoma: SCC) on January 25, 2000, and concurrent chemoradiotherapy (CCRT) was applied. After the treatment, a remnant tumor in the larynx was found by biopsy. He was followed using UFT at 400mg/day because he had refused surgery. Pulmonary metastasis was detected by chest CT on June 14, 2001, and the administration of S-1 was started. After 2 courses, the mass in the lung disappeared, and the primary lesion was also judged to be a complete response(CR). The administration of S-1 is still continuing and remnant tumors have not been found. Case 2, a 76-year-old man, was diagnosed with hypopharyngeal carcinoma (T3N2bM0, SCC) on December 14, 2001, and CCRT was applied resulting in CR in the hypopharynx and the neck. He was followed using UFT at 300 mg/day after discharge. A supraclavicular lymph node became palpable on March 27, 2003. Pathological examination by fine needle aspiration cytology showed SCC, class V. After 2 courses administering S-1 at 100mg/day, the supraclavicular lymph node disappeared. S-1 was changed to UFT at 300 mg/day on July 31, 2003, because adverse events of grade 3 appeared. Administration of UFT was continued for one year. No recurrence has been found for 5 years.

Objective: To explore the potential clinical application of the oncolytic activity of cyclooxygenase 2 (COX-2) promoter-based, conditional, replication-selective adenovirus vector for hypopharyngeal squamous cell carcinoma., Design: In vivo study and retrospective study., Setting: Kobe University Hospital, Kobe, Japan., Subjects: Expression of COX-2 in hypopharyngeal cancers treated at Kobe University Hospital was immunohistochemically investigated. In addition, nude mice bearing human hypopharyngeal cancer cells (H891) were used to analyze oncolytic activity of a conditional replication-selective adenovirus vector in which the expression of E1a, required for viral replication, is controlled by the COX-2 promoter Ad-COX2-E1a., Results: In vivo assays showed significant growth suppression in the murine hypopharyngeal model. Cyclooxygenase 2 expression was observed in 75.3% of hypopharyngeal cancers, especially in differentiated tumor cells (P = .001; r = 0.433)., Conclusion: In this study, we demonstrated the potential of oncolytic therapy using the COX-2-promoter based, conditional, replication-selective adenovirus for COX-2-expressing hypopharyngeal squamous cell carcinomas.

Conclusion: The results presented here provide evidence of the enhancing effect of oral fluoropyrimidine derivative S-1 in concomitant chemoradiotherapy for head and neck cancer and further insights into its biological mechanism., Objective: To investigate the additive effect of S-1 and radiation for human hypopharyngeal cancer., Materials and Methods: Nude mice bearing hypopharyngeal cancer cells (H891) were used for an in vivo model. S-1 was administered at a volume of 0.01 mg/g body weight per mouse for 14 days, and tumors were irradiated with 2.0 Gy on days 1 and 8. Mice treated with either radiation or S-1 alone were used as controls. The growth of tumors in each group was measured and, after completion of the treatment, a focused DNA array was used to determine mRNA expression levels in the tumors of 132 genes related to 5-fluorouracil (5-FU), radiation or carcinogenesis., Results: The additive antitumor effect of S-1 and radiation was statistically confirmed on day 14 (p=0.01). DNA array assay showed significant changes in expression of several genes, including DNA repair gene POLD, angiogenesis-related genes bFGF and TP, DNA topoisomerase TOP2A, and nucleoside transporter gene ENT1.

Objective: Nafamostat mesilate (FUT-175), a synthetic serine protease inhibitor, has antitumor activities toward adenocarcinoma, e.g., colon cancer. However, its antitumor effects on other types of cancer have been less extensively studied. We investigated the biological activities of Nafamostat mesilate on cell proliferation, cell-invasive potential and growth factor production in head and neck squamous cell carcinoma (HNSCC)., Methods: Two human HNSCC cell lines established in our department, YCU-L891 and -H891, and a human vulvar squamous cell carcinoma cell line, A431, were examined for the effect of Nafamostat mesilate. The effects on cell growth were evaluated using the MTT assay. The effects on the relative expression levels of mRNA were measured by quantitative RT-PCR. Cytokine secretion was analyzed by enzyme-linked immunosorbent assay., Results: Nafamostat mesilate inhibited the proliferation of two HNSCC cell lines, YCU-L891 and YCU-H891, and A431. In these cell lines, Nafamostat mesilate down-regulated both matrix metalloproteinase (MMP)-2 and -9. In addition, it reduced the productions of vascular endothelial growth factor (VEGF) and transforming growth factor beta1 (TGF-beta1) by the tumor cells., Conclusion: Our results suggest that Nafamostat mesilate has potential for use as a treatment against local growth, invasion and metastasis of squamous cell carcinoma.

Objectives: Concurrent chemoradiotherapy (CCR) was given for the previously untreated T4 hypopharyngeal and laryngeal squamous cell carcinoma patients and the response and survival rates were evaluated., Patients and Methods: A total of 23 patients, namely, 15 for hypopharynx and 8 for larynx were eligible. These patients were given cisplatin and 5-fluorouracil based chemotherapeutic regimens with conventional radiotherapy for a total dose of 66.6-70.2 Gy., Results: Ten out of the 15 hypopharyngeal carcinoma patients and 4 out of the 8 laryngeal carcinoma patients showed a complete response at the primary sites. The 5-year disease-specific survival rate was 59.4% in all the patients, 51.9% in the hypopharyngeal carcinoma patients, and 71.0% in the laryngeal patients. Seven out of the 12 resectable hypopharyngeal carcinoma patients and 4 out of 8 laryngeal carcinoma patients were able to do without total laryngectomy., Conclusions: Based on these results, the survival rate in the hypopharyngeal and laryngeal T4 carcinoma patients treated by CCR seems to be satisfactory and the possibility of organ preservation for the advanced patients is indicated.

We treated a patient with hypopharyngeal fibromatous polyp and speculated the mechanism of this disease. Fibromatous polyp, consisting of fibrous tissue hyperplasia with small vessels, fatty cells and inflammatory cells, is a clinically diagnostic name. Most of pharyngeal fibromatous polyps are arising from the palatine tonsil, and those from the pharyngeal epithelium are rare. The greater part of hypopharyngeal tumors is squamous cell carcinomas, and benign tumors are really uncommon. Fibromatous polyp is not thought to be a true tumor, but the symptoms are almost the same as tumorous diseases, e.g., discomfort in the throat, swallowing difficulty and respiratory distress. Complete resection is used as the treatment method. We operated on this patient under a laryngoscope and successfully resected the polyp. Five months after the operation, there is no sign of recurrence and the patient has no symptoms. This type of polyp is considered to enlarge gradually and it can cause asphyxia and/or dysphagia, so complete ablation should be performed as soon as possible.

Myxofibrosarcoma is common in the extremities, but rare in the head and neck region. Hypopharyngeal myxofibrosarcoma has not been reported previously. We report the first case of a patient with myxofibrosarcoma of the hypopharynx. We examined this patient once a month after the operation, and there has been no local recurrence and no distant metastasis. Sarcomas are rare in the hypopharynx, but we have to bear in mind their possibility. Though a low-grade myxofibrosarcoma is a low-grade malignancy, complete resection should be done. We have to pay more attention planning the treatment for neoplastic diseases.

Objective: To study the efficacy of intensive chemotherapy for simultaneous triple primary cancers of the hypopharynx, esophagus, and stomach., Study Design: Retrospective case study., Methods: From April 2000 to March 2002, we treated 4 patients who had simultaneous triple primary cancers, including hypopharyngeal, esophageal, and gastric carcinomas. These 4 patients were designated as the objects for analysis, and the treatment modality for simultaneous multiple primary cancer cases was examined., Results: In 3 of 4 patients, all 3 primary cancers could be controlled by intensive induction chemotherapy and concurrent chemoradiotherapy for hypopharyngeal cancer and by endoscopic mucosal resection or argon plasma coagulation for esophageal and gastric carcinomas., Conclusions: In the treatment modality for simultaneous multiple primary cancers, including head and neck cancer, it is important to select intensive systemic chemotherapy and decide the order for treating each primary lesion in consideration of each patient's curability and prognosis.

Adult hypopharyngeal haemangioma is an uncommon neoplasm. We present three cases of adult hypopharyngeal haemangioma which were successfully treated with a neodymium: yttrium-aluminium-garnet (Nd: YAG) laser in our hospital between 2000 and 2003. The patients in this series experienced no untoward events from the use of the laser. Excessive bleeding and airway problems were not encountered. Postoperative pain was minimal. Excellent long-term function and a full resolution of symptoms can be obtained using Nd: YAG laser. The laser provides a bloodless field and complete healing of the hypopharynx, without stenosis or scar formation.

We analyzed the relationship between clinical response to neo-adjuvant chemotherapy including 5-fluorouracil (5-FU) in patients with hypopharyngeal carcinoma (HPC) and thymidylate synthase (TS) expression in their tumors. TS expression was evaluated with immunohistochemical staining techniques on biopsy specimens from HPC patients. TS immunostaining was divided into four levels (TS0-TS3) according to its level and pattern. The relationship between prognosis, tumor size, nodal status, differentiation of tumor cells and TS expression were also investigated. There was a statistically significant association between the level of TS expression and tumor size (p < 0.01). In terms of the effectiveness of chemotherapy, tumor differentiation, nodal status and prognosis, a statistical difference was not found in TS expression. These results suggest that the level of TS expression may show the degree of tumor proliferation, but may not necessarily be useful to obtain a response to chemotherapy including other drugs, e.g., cisplatin and other derivatives of platinum.

Thirty-seven biopsy specimens from primary sites, 18 surgically removed metastatic neck nodes, and 18 surgically removed primary sites from 37 patients with hypopharyngeal carcinoma (HPC) were evaluated for the presence of Epstein-Barr Virus (EBV) infection by in situ hybridization (ISH) and polymerase chain reaction (PCR). Although some of normal lymphocytes in 6 of 18 metastatic nodes were positive by ISH, there were no positive results from HPC tumor cells themselves. Our results indicate that EBV-infected non-neoplastic cells such as lymphocytes can be a cause of false positivity, if a study were conducted with PCR alone. Because ISH for EBV-encoded early RNAs was highly sensitive, even more sensitive than PCR from paraffin-embedded samples in our study, this method should be the first choice for identification of EBV infection to avoid false positives.

Hypopharyngeal carcinoma (HPC) has a poor prognosis. We investigated the expression of cyclin D1 in 34 advanced HPCs, and the value of cyclin D1 expression was evaluated as a predictive marker in terms of the prognosis of HPC, compared with other clinical factors. Using immunohistochemical staining, 20 of 34 patients showed positive immunoreactivity for cyclin D1. The statistical trend of the survival rate was lower in the cyclin D1-positive patients than in the cyclin D-negative ones (p = 0.0805). The predictive factors for the survival rate were effectiveness of neo-adjuvant chemotherapy (F = 8.698) (p = 0.0066), cyclin D1 expression (F = 6.244) (p = 0.0191) and N classification (F = 5.037) (p = 0.0335). The cyclin D1-positive patients had approximately four-fold higher mortality than the cyclin D1-negative ones. These data indicate that the expression of cyclin D1, in advanced patients with hypopharyngeal carcinoma is a useful marker for prognosis.

A carotid artery reconstruction was performed on two patients of head and neck cancer with infiltration into the carotid artery. To detect any possibility of cerebral ischemia at the time of ligation of the carotid artery, a temporary occlusion test of the internal carotid artery with a balloon catheter (balloon Matas test) was performed in both cases. An artificial vessel (Case 1) and a greater saphenous vein (Case 2) were used as an implanted vessel. No neurological sequelae were observed during or after the surgery in these cases. With a recent advance in various imaging diagnosis and an improvement in surgical techniques, the radical treatment including carotid artery reconstruction is expected to improve the prognosis for the cases demonstrating tumor infiltration into the carotid artery.