Combined treatment with D-allose, docetaxel and radiation inhibits the tumor growth in an in vivo model of head and neck cancer.

The present study was designed to evaluate the effect of one rare sugar, D-allose, on normal human cells and cutaneous tissue, and to investigate the radiosensitizing and chemosensitizing potential of D-allose in an in vivo model of head and neck cancer. Results indicated that D-allose did not inhibit the growth of normal human fibroblasts TIG-1 cells, and no apoptotic changes were observed after D-allose and D-glucose treatment. The mRNA expression levels of thioredoxin interacting protein (TXNIP) in TIG-1 cells after D-allose treatment increased by 2-fold (50.4 to 106.5). Conversely, the mRNA expression levels of TXNIP in HSC3 cancer cells increased by 74-fold (1.5 to 110.6), and the thioredoxin (TRX)/TXNIP ratio was markedly reduced from 61.7 to 1.4 following D-allose treatment. Combined multiple treatments with docetaxel, radiation and D-allose resulted in the greatest antitumor response in the in vivo model. Hyperkeratosis, epidermal thickening and tumor necrosis factor-α immunostaining were observed following irradiation treatment, but these pathophysiological reactions were reduced following D-allose administration. Thus, the present findings suggest that D-allose may enhance the antitumor effects of chemoradiotherapy whilst sparing normal tissues.

Single injection of basic fibroblast growth factor to treat severe vocal fold lesions and vocal fold paralysis.

OBJECTIVES/HYPOTHESIS: Severe vocal fold lesions such as vocal fold sulcus, scars, and atrophy induce a communication disorder due to severe hoarseness, but a treatment has not been established. Basic fibroblast growth factor (bFGF) therapies by either four-time repeated local injections or regenerative surgery for vocal fold scar and sulcus have previously been reported, and favorable outcomes have been observed. In this study, we modified bFGF therapy using a single of bFGF injection, which may potentially be used in office procedures. STUDY DESIGN: Retrospective chart review. METHODS: Five cases of vocal fold sulcus, six cases of scars, seven cases of paralysis, and 17 cases of atrophy were treated by a local injection of bFGF. The injection regimen involved injecting 50 µg of bFGF dissolved in 0.5 mL saline only once into the superficial lamina propria using a 23-gauge injection needle. Two months to 3 months after the injection, phonological outcomes were evaluated. RESULTS: The maximum phonation time (MPT), mean airflow rate, pitch range, speech fundamental frequency, jitter, and voice handicap index improved significantly after the bFGF injection. Furthermore, improvement in the MPT was significantly greater in patients with (in increasing order) vocal fold atrophy, scar, and paralysis. The improvement in the MPT among all patients was significantly correlated with age; the MPT improved more greatly in younger patients. CONCLUSIONS: Regenerative treatments by bFGF injection­even a single injection­effectively improve vocal function in vocal fold lesions. LEVEL OF EVIDENCE: 4

[The Correlation between the Size of Vocal Polyps, Vocal Nodules and Vocal Dysfunction, before and after Laryngeal Microsurgery].

When we operate on a vocal polyp or a vocal nodule with laryngeal microscopy, we always carefully measure their length and width then multiply the length by the width to get the area. We examined whether there is a correlation between the area of these lesions and the acoustic analysis of voice. Before the surgery and one month post-operation, we checked five acoustic parameters, maximum phonation time (MPT), range of voice, mean air flow rate (MFR) and acoustic analyses (jitter% and shimmer%). By doing this, we could arrive at the improvement rate of each of the five acoustic parameters. We examined whether there was a correlation between the lesion area and acoustic parameters before surgery and the improvement rates of these acoustic parameters. Examinations of polyps showed a correlation between the size and range of voice and Jitter% pre-operation, and showed a correlation between the size and improvement rate of range of voice, MFR, Jitter% and Shimmer% post-operation. On the other hand, examination of nodules showed a correlation only between the size and range of voice pre-operation. Next we examined the correlation between the size and these acoustic parameters in the Elite vocal performer (EVP) group and extra EVP group. In the examinations of polyps, the EVP group showed a lower correlation between the size and acoustic parameters than in the extra EVP group. On the other hand, in the examinations of nodules, correlation between the size and acoustic parameters was low in both the EVP and extra EVP group.

Clinical outcomes of nedaplatin and S-1 treatment with concurrent radiotherapy in advanced head and neck cancer.

CONCLUSION: Nedaplatin and S-1 treatment with concurrent radiotherapy was effective, with acceptable toxicities. This regimen does not require extensive intravenous hydration and continuous infusion. Nedaplatin and S-1 may contribute to better clinical outcomes and improve quality of life for patients. OBJECTIVES: We retrospectively analyzed the clinical efficacy and toxicity of concurrent chemoradiotherapy with nedaplatin and S-1 for head and neck squamous cell cancer. METHODS: Forty-six patients with oropharyngeal, hypopharyngeal, and laryngeal cancer were treated with S-1 on days 1 through 14 and nedaplatin on day 1 every 4 weeks for two cycles of radiotherapy. Therapeutic responses and adverse events were assessed. RESULTS: Primary site tumors and neck lymph nodes exhibited complete response rates of 91% and 64.3%, respectively. The 4-year relapse-free survival and overall survival rates were 76.2% and 85.3%, respectively. The main grade 3 and 4 toxicities were mucositis (30%), leukopenia (30%), anorexia (22%), dermatitis (15%), and thrombocytopenia (9%).

Effects of D-allose in combination with docetaxel in human head and neck cancer cells.

In this study we investigated the combined effects of docetaxel and d-allose in HSC3 human oral carcinoma cells. The dose enhancement ratios at the 25% survival level were 1.3 and 1.71 for combined treatment with 10 or 25 mM D-allose, respectively. Apoptosis was significantly increased by addition of D-allose. Additionally, a synchronous increase in the G(2)/M-phase population was observed after docetaxel plus D-allose treatment. In vivo experiments revealed that docetaxel plus D-allose was more effective than either agent alone. Thus, D-allose enhanced the anticancer effects of docetaxel, and combined treatment may be useful to achieve clinical efficacy with reduced toxicity.

Phonological outcome of laryngeal framework surgery by different anesthesia protocols: a single-surgeon experience.

CONCLUSION: Similar to combined arytenoid adduction and medialization laryngoplasty (i.e. combined surgery) under local anesthesia, general anesthesia by intubation or by the laryngeal mask airway (LMA) method significantly improves phonological outcome. Thus, laryngeal framework surgery under general anesthesia is a promising surgical approach for selected patients with unilateral vocal cord paralysis (UVCP). OBJECTIVE: The advantages of laryngeal framework surgery under local anesthesia have been described, but no studies exist concerning the difference in phonological outcome of laryngeal framework surgery performed under general anesthesia. To add new information, we retrospectively investigated the phonological outcome of the combined surgery performed under three different anesthesia protocols. METHODS: Thirty-nine consecutive patients with severe UVCP underwent the combined surgery under three anesthesia protocols performed by a single surgeon: (1) under general anesthesia by intubation, (2) under general anesthesia using LMA, and (3) under local anesthesia. RESULTS: Under all anesthesia protocols, the vocal cords of most patients could be positioned such that the best vocal outcome could be expected. Statistical analyses demonstrated improved maximum phonation time and mean airflow rate, and grade, roughness, breathiness, asthenia, and strain (GRBAS) scale in all patients, regardless of their anesthesia protocol. Furthermore, of the three protocols, local anesthesia had the shortest operation time.

Enhancement of the radiation effects by D-allose in head and neck cancer cells.

The aim of this study was to investigate the radiosensitizing potential of D-allose in human head and neck cancer cells. HSC-3 cells were treated with or without D-allose for 6 h and then irradiated (2-6 Gy). The combination of D-allose and radiation was more effective than either agent alone. The radiation enhancement ratios at the 37% survival level were 1.61 and 2.11 for 10 mM and 25 mM D-allose treatment, respectively. The combination of D-allose and radiation also reduced the cell proliferation in 3D culture experiments. Although the mRNA expression of TXNIP was not increased by radiation alone, combined use with D-allose markedly elevated TXNIP expression. The combination of D-allose and radiation significantly induced intracellular reactive oxygen species (ROS) and apoptosis compared to that induced by either agent alone. This study shows that D-allose enhances the effect of radiation, suggesting a potential clinical application of combination treatment with D-allose and radiation for head and neck cancer.

Clinicopathological significance of cyclooxygenase-2 expression in hypopharyngeal squamous cell carcinoma.

The purpose of this study was to determine the expression of cyclooxygenase-2 (COX-2) in normal epithelium, dysplasia and squamous cell carcinoma of the hypopharynx and to investigate associations with clinicopathological factors and survival. Seventy-five patients with hypopharyngeal squamous cell carcinomas (HPSCC) who underwent surgical treatment at the Department of Otolaryngology, Osaka Medical Center for Cancer and Cardiovascular Diseases, were investigated. COX-2 expression was determined by immunohistochemistry and 97.3% (73/75) of samples displayed immunostaining in tumor cells. COX-2 staining was localized mainly in the cytoplasm (73/75) and was rare in stromal cells (2/75). Over half of the areas of dysplastic cells adjacent to carcinomas also showed COX-2 staining (41/70, 58.6%). There were no significant correlations between the COX-2 expression and tumor size, location and tumor growth type, T- and N-stage, tumor recurrence, lymph node metastasis and survival in this study. COX-2 expression thus does not appear to have a prognostic significance for hypopharyngeal SCC although there was a tendency for higher values in T3/T4 than T1/T2 cases. Furthermore, COX-2 was found to be more strongly expressed in poorly-differentiated than in moderately/well-differentiated carcinomas. In this study group, COX-2 was up-regulated not only in SCCs but also in the dysplastic lesions of the hypopharynx, suggesting that COX-2 inhibition may be a useful chemopreventive strategy.