Kikuo Sakamoto

Expression and Distribution of CD44 and Hyaluronic Acid in Human Vocal Fold Mucosa

Objectives: Expression of CD44 (a cell surface receptor for hyaluronic acid) and the distribution of hyaluronic acid were examined in the human vocal fold mucosa. Methods: Light microscopic investigation was carried out on 10 normal larynges of newborn, infant, younger adult, and older adults with Alcian blue staining, a hyaluronidase digestion study, and immunohistochemistry for CD44. Results: Before the appearance of hyaluronic acid in the newborn vocal fold mucosa, CD44 was expressed on the stellate cells in the macula flava and on the fibroblasts in Reinkes space. During infancy, hyaluronic acid appeared and was distributed in the vocal fold mucosa. Many more stellate cells in the macula flava showed CD44 expression, and a large amount of hyaluronic acid was present around the infant stellate cells; however, the fibroblasts in Reinkes space expressed little CD44. During adulthood, hyaluronic acid was distributed in the vocal fold mucosa. Almost all of the stellate cells in the macula flava showed CD44 expression, and much hyaluronic acid existed around the stellate cells in the adult macula flava. However, fibroblasts in the adult Reinkes space expressed little CD44, and hyaluronic acid density in that space was lower than that in the macula flava. Conclusions: Stellate cells in the macula flava and CD44 cooperatively play important roles in maintaining hyaluronic acid in the human vocal fold mucosa as a vibrating tissue.

Clinical study of parapharyngeal space tumours

This study reviewed 24 cases of parapharyngeal space tumour treated at Kurume University Hospital between 1990 and 2007. Histological diagnoses were generally obtained from the excised tumour (22/24). Seventy-seven per cent of the parapharyngeal space tumours were benign and 23 per cent were malignant. Thirty-eight per cent (eight of 22) of these tumours were pleomorphic adenomas and 23 per cent (five of 22) were schwannomas. A transparotidectomy and transcervical approach were used in 88 per cent (15/17) of benign tumours. A mandibular swing approach was used for one malignant tumour. Post-operative complications were identified in 16 of 22 patients. The most common complication, facial nerve paralysis, was identified in eight patients, and seven of these patients demonstrated first bite syndrome. In consideration of the high incidence of post-operative complications, the surgical approach should therefore be carefully selected when treating patients with parapharyngeal space tumours.

Antitumor effects of systemic and local immunization with a CTL-directed peptide in combination with a local injection of OK-432.

PURPOSE: The accumulation of T cells into the tumor site is crucial for the elicitation of in vivo antitumor effects after cancer vaccination. In this study, we investigated the antitumor effects and associated mechanisms of action that were induced by systemic and local immunization with a CTL-directed peptide in combination with a peritumoral injection of a streptococcal preparation, OK-432. EXPERIMENTAL DESIGN AND RESULTS: The human SART3(315-323) peptide, which has the potential to induce human leukocyte antigen-A24-restricted CTLs, not only has the same amino acid sequence as the mouse SART3, but also has the capacity for binding to H-2K(d) molecules. Therefore, the SART3(315-323) peptide could be used as a tumor antigen-derived peptide in H-2(d) mice. Systemic immunization with the SART3(315-323) peptide and the subsequent peritumoral injection of both the SART3(315-323) peptide and OK-432 effectively induced peptide-specific and colon26 carcinoma-reactive CTLs in BALB/c mice. The combination therapy suppressed the growth of s.c. established colon26 carcinoma. The accumulation of both CD8(+) and CD4(+) T cells into the tumor site was more apparent in mice treated with the combination therapy than in those treated with other protocols. In addition, the level of IgG reactive to the administered SART3(315-323) peptide increased in mice that were treated with the combination therapy. CONCLUSION: These results indicate that antitumor effects could be efficiently induced by a combination therapy that included systemic and local immunization with a CTL-directed peptide together with a local injection of OK-432.

Surgical approach to a giant fibrolipoma of the supraglottic larynx.

This paper describes the surgical procedures for a fibrolipoma that first appeared as a giant tumour in the hypopharynx and extended to the cardiac antrum of the oesophagus. At the initial surgery, a pedunculated tumour originating from the left arytenoid of the larynx was found to occupy the cervical as well as thoracic oesophagus and was thus removed through a lateral pharyngectomy. A histological examination revealed fibrolipoma. However there was a recurrence of the tumour in the arytenoid and the patient suffered from dysponea. In addition, a submucosal tumour was also found in the left false vocal fold. At the second surgery, the masses in the arytenoid and false vocal fold were subtotally removed without damaging the mucosa. The mucosa of the arytenoid was sutured to the thyropharyngeal muscle on the same side and the arytenoid swelling disappeared almost completely. The post-operative course has been uneventful for more than two years.

Laboratory data and treatment outcomes of head and neck tumor patients in the elderly.

OBJECTIVE To elicit the factors influencing the choice of treatment and the prognosis of elderly patients, we studied the clinical and laboratory data of head and neck tumor patients. The patients were divided into two groups (group A: younger than 75, group B: 75 years of age or older) and the treatment outcomes as well as the features of the laboratory data were analyzed. METHODS The clinical records of 1350 patients (888 males, 462 females) with head and neck tumors who received their initial treatment at our hospital were reviewed. The collected data including age, the site of the primary lesion, pre-treatment health states, pre-operative laboratory results were examined. According to the treatment policy, we grouped the patients according to whether or not they had received the standard therapy for the disease and then analyzed their treatment outcomes. RESULTS Standard therapy was not performed in 62 (5.6%) of the 1114 patients in group A and in 43 (18.2%) of the 236 patients in group B. A further analysis performed in group B (elderly patients) revealed that standard therapy was performed in 193 patients, while 43 received non-standard therapy. The prognosis for the non-standard therapy cases was poor. The averages of the laboratory test findings between groups A and B were compared, but no marked differences were observed. However, differences were observed in the ratio of patients whose data were in the normal range between group A and group B. When the laboratory data were compared between the standard and non-standard groups of the elderly, serum albumin and CBC (especially hemoglobin) showed a close relationship to the treatment modality. CONCLUSION The ratio of patients who did not receive standard therapy was high in the age group of 75 years or older. The prognosis of patients with head and neck tumors is therefore considered to depend on whether or not a patient receives the standard therapy against the disease. The pre-treatment clinical data and the laboratory findings vary markedly among elderly patients 75 years of age or older. Regarding the treatment of head and neck tumors in the elderly, the laboratory data and clinical conditions of each individual patient should be checked carefully and every possible means should be employed in order to allow such patients to receive the standard therapy whenever possible.

Supraglottic carcinoma treatment results analysed by therapeutic approach

This study reviewed 161 patients with supraglottic squamous cell carcinoma who underwent radical therapy at Kurume University Hospital between 1989 and 2003. The five-year survival rate was 89 per cent in patients with stage III disease and 75 per cent in stage IV patients, thus demonstrating favourable results even for patients with advanced cancer. The five-year local control rate and the laryngeal preservation rate were poor in patients with T3 tumours (being 75 per cent for both), but the overall five-year local control rate for all patients was 86 per cent. Laser surgery plus chemo-radiotherapy was the most frequently used treatment. The local control rates and laryngeal preservation rates were poor in patients with tumour infiltration to the glottis and the laryngeal ventricle. In conclusion, the indications for combination laser therapy for supraglottic carcinoma should in future be extended, and the type and number of chemotherapy courses for this cancer should be further clarified.

The immunohistochemical expression of p21WAF1/Cip1 and Proliferating cell nuclear antigen in laryngeal squamous cell carcinomas.

The purpose of this study was to assess the significance of the expression of p21WAF1/Cip1 and proliferating cell nuclear antigen (PCNA) in human laryngeal squamous cell carcinomas. Forty-eight patients (25 supraglottic, 23 glottic) who had undergone operations between 1998 and 2003 were included in this study. The Envision immunohistochemistry method was utilized to stain these tissue specimens. The results showed that the immunostaining of p21WAF1/Cip1 do not show any correlation with differentiation, N stage, metastasis, survival, recurrence or the laryngeal site of involvement. A significant inverse correlation was detected between p21WAF1/Cip1 and the T stage. In contrast, the percentage of PCNA labelled cells showed a significant correlation with the T stage, but not with other clinicopathological parameters. There were differences in the expression of p21WAF1/Cip1 and PCNA between the supraglottic and the glottic carcinomas. In conclusion, our findings suggest that p21WAF1/Cip1 and PCNA may play an important role in the progression of carcinoma of the supraglottic larynx.

Treatment of Subglottic Carcinoma

A retrospective review was performed on 12 patients (10 male and 2 female ; mean age of 62.1 years) with subglottic cancer who received initial treatment at Kurume University Hospital between 1979 and 2006. In T classification, there were 4 T2 cases and 8 T4 cases. In N classification, there were 8 NO cases, 3 N1 cases and 1 N2 case. 3 were at stage 2 and 9 were at stage 4a. The 3-year and 5-year survival rates as determined by the Kaplan-Meier method were 81.8% and 70.1% respectively. The 3-year and 5-year survival rates for cases at stage T2 were both 75%, whereas those at T4 were 83.3% and 62.5%. 6 patients died. 3 patients died of the primary disease (lymph node death : 1, distant metastasis death : 2) . Total laryngectomywith bilateral paratracheal neck dissection was performed in 9 cases. (3 T2 cases and 6 T4 cases) . Radiotherapy as additional treatment was performed on 4 out of 9 cases. Laryngeal preservation operations were performed in 3 cases (1 T2 cases and 2 T4 cases) . Radiotherapy and chemotherapy were performed in 2 cases while super-selective intra-arterial chemotherapywith radiotherapy was performed in 1 case. This particular patient did not experience recurrence. It is conceivable that super-selective intra-arterial chemotherapy with radiotherapy is one of the more effective treatments in laryngeal preservation.

Expression of cluster of differentiation 9 glycoprotein in benign and malignant parotid gland tumours.

OBJECTIVES This study aimed to clarify the significance of cluster of differentiation 9 glycoprotein gene expression in human parotid gland tumours. METHODS We retrospectively analysed immunohistochemical staining for cluster of differentiation 9 glycoprotein in parotid gland tumours. RESULTS Cluster of differentiation 9 glycoprotein was consistently detected in the normal parotid gland. Regarding benign parotid gland tumours, cluster of differentiation 9 glycoprotein was present in 13 of 18 pleomorphic adenomas, in all Warthin tumours tested (21/21) and in all cases of basal cell adenoma tested (four of four). In contrast, positive staining for cluster of differentiation 9 glycoprotein was less often observed in malignant parotid tumours. Cluster of differentiation 9 glycoprotein was present in 11 of 14 mucoepidermoid carcinomas, in two of five acinic cell carcinomas and in two of five adenoid cystic carcinomas. CONCLUSIONS There was a statistically significantly reduced expression of cluster of differentiation 9 glycoprotein in malignant parotid gland tumours, compared with benign parotid gland tumours (p < 0.05). These results suggest that a low level of cluster of differentiation 9 glycoprotein expression in parotid gland tumours may be associated with malignancy.

Clinical investigation of obstructive sleep apnea syndrome in female patients

Few papers have addressed gender differences in sleep apnea syndrome (SAS). We investigated the relation between SAS and gender. Five hundred and eighteen patients underwent polysomnography (PSG) at Kurume University Hospital between May 2002 and April 2004. In 386 patients (319 male, 67 female, average age of 50 years old) who fulfilled the criteria of SAS (apnea-hypopnea index ‹AHI›≥5), age, body mass index (BMI), AHI, abnormality of maxillo-facial form (maxilla, mandibular retrusion) and tonsil hypertrophy were examined. The AHI of males was higher than that of females (p=0.0553), but there was no difference in BMI. In regard to the maxillo-facial form and tonsil hypertrophy, abnormal findings were found in male patients, but there was no difference in mandibular retrusion. Forty-seven (70.1%) of the 67 female patients were in postmenopause. When data were compared between females in premenopause and postmenopause, BMI and AHI were significantly higher in premenopausal patients. In regard to the mandibular-facial form, postmenopausal females showed abnormality. On the other hand, tonsil hypertrophy was predominantly found in premenopausal females. In comparison to the number of SAS cases in male and female patients, there were fewer mandibular-facial form abnormalities in females. Therefore, the diagnosis of SAS in females is rather difficult unless PSG is done. In postmenopausal females, AHI was relatively high despite the fact that they were not obese. These results suggest that functional rather than qualitative changes are important for understanding the characteristics of SAS in postmenopausal females.