Satoru Takebayashi

Cyclin D1 overexpression correlates with poor prognosis in patients with tongue squamous cell carcinoma.

Tongue squamous cell carcinoma makes up a large percentage of head and neck cancers, and the incidence among young patients is increasing. The aim of this study was to reveal the correlation between cyclin D1 (CCND1) expression and clinical and histologic features. We performed an immunohistochemical study on the level of CCND1 expression in tumor specimens obtained from 94 patients with tongue squamous cell carcinoma. The relationship between the expression and the following features such as age, sex, smoking and alcohol intake history, T, N, histologic grade, and multiple primary cancer was analyzed. Eighteen patients (19%) showed CCND1 overexpression (tumor cell nuclei positivity >/=50%). The 5-year survival rate of high CCND1 expressors was 39%, which was significantly poor (p=0.04). N classification correlated with CCND1 expression. CCND1 overexpression is associated with poor survival associated with progression of lymph node spread in patients with tongue squamous cell carcinomas. CCND1 expression may be a useful biologic marker for prognosis.

Immunohistochemical Analysis of Small Cell Carcinoma of the Head and Neck: A Report of Four Patients and a Review of Sixteen Patients in the Literature with Ectopic Hormone Production

Small cell carcinoma (SCC) occurs mostly in the lung, and in some patients is accompanied by production of ectopic hormones. Small cell carcinoma of the head and neck is very rare. We report 4 patients with SCC of the head and neck (larynx, tonsil, maxillary sinus, and parotid gland). The patient with SCC of the maxillary sinus demonstrated a high level of plasma serotonin and overexpression of parathyroid hormone; however, he did not show any related symptoms. The patient with SCC of the tonsil showed the syndrome of inappropriate secretion of antidiuretic hormone associated with antidiuretic hormone hyperproduction at the terminal stage. In the literature, 16 patients with SCC of the head and neck with ectopic hormone production have been reported. Antidiuretic hormone and adrenocorticotropic hormone were the hormones that caused clinical symptoms (paraneoplastic syndromes). We believe that the evaluation of hormonal syndromes is valuable for diagnosis and treatment.

Loss of chromosome arm 18q with tumor progression in head and neck squamous cancer.

Loss of 18q was analyzed in 21 sets of head and neck squamous cell carcinoma (HNSCC) cell lines derived from primary and secondary tumors in the same patients. Only 3 of the 21 cell line pairs had no loss of 18q. In the remaining 18 sets, loss of heterozygosity (LOH) affecting 18q was found in either the primary or the secondary lines or both. In every case but one, the same chromosome was affected in both the primary and secondary cell lines. In 8 sets, the 18q loss occurred in the primary tumor and remained stable through the subsequent tumor progression. The primary and secondary lines differed in 18q loss in 10 of 18 (56%) cases with 18q LOH. In 3 of the 10 pairs that differed, 18q LOH was found in only the primary line, indicating that the loss developed after the metastatic or recurrent tumor population had diverged from the primary tumor population. In the other 7 pairs, 18q LOH developed or progressed with tumor recurrence or metastasis. Of these, 3 of 7 had 18q LOH in only the secondary lines, and 4 of 7 had 18q LOH in both the primary and secondary lines, but the extent of LOH was greater in the secondary lines than in the primary lines, indicating that additional rearrangements of the same chromosome occurred with progression. These cases showed that interstitial loss often progresses to consolidated loss in vivo. However, in vitro, the cell lines from the primary tumors with interstitial loss maintain those chromosomes over long‐term culture. LOH on 18q in cell lines from previously untreated primary tumors was significantly associated with advanced tumor stage (P = 0.0242) and decreased survival (P = 0.0453). The findings are consistent with the concept that 18q LOH is an event associated with tumor progression and suggest that inactivation and loss of one or more genes on 18q contributes to aggressive tumor behavior.

Epigenetic Inactivation of Galanin Receptor 1 in Head and Neck Cancer

Purpose: One copy of the galanin receptor 1 (GALR1) locus on 18q is often deleted and expression is absent in some head and neck squamous cell carcinoma (HNSCC) cell lines. To determine if loss of heterozygosity and hypermethylation might silence the GALR1 gene, promoter methylation status and gene expression were assessed in a large panel of HNSCC cell lines and tumors. Experimental Design: Promoter methylation of GALR1 in 72 cell lines and 100 primary tumor samples was analyzed using methylation-specific PCR. GALR1 expression and methylation status were analyzed further by real-time PCR and bisulfite sequencing analysis. Results: The GALR1 promoter was fully or partially methylated in 38 of 72 (52.7%) HNSCC cell lines but not in the majority 18 of 20 (90.0%) of nonmalignant lines. GALR1 methylation was also found in 38 of 100 (38%) primary tumor specimens. Methylation correlated with decreased GALR1 expression. In tumors, methylation was significantly correlated with increased tumor size (P = 0.0036), lymph node status (P = 0.0414), tumor stage (P = 0.0037), cyclin D1 expression (P = 0.0420), and p16 methylation (P = 0.0494) and survival (P = 0.045). Bisulfite sequencing of 36 CpG sites upstream of the transcription start site revealed that CpG methylation within transcription factor binding sites correlated with complete suppression of GALR1 mRNA. Treatment with trichostatin A and 5-azacytidine restored GALR1 expression. In UM-SCC-23 cells that have total silencing of GALR1, exogenous GALR1 expression and stimulation with galanin suppressed cell proliferation. Conclusions: Frequent promoter hypermethylation, gene silencing, association with prognosis, and growth suppression after reexpression support the hypothesis that GALR1 is a tumor suppressor gene in HNSCC.

Hyperbaric Oxygen Therapy as Adjuvant Treatment for Idiopathic Sudden Sensorineural Hearing Loss after Failure of Systemic Steroids

We evaluated the outcomes of and prognostic factors for idiopathic sudden sensorineural hearing loss (ISSNHL) treated with adjuvant hyperbaric oxygen therapy (HBOT). A retrospective review of clinical data was performed for 167 patients with ISSNHL who failed to respond to systemic steroids and were treated by adjuvant HBOT at Shizuoka Saiseikai General Hospital. We analysed the clinical outcomes, the averaged 5-frequency hearing level after systemic steroids, patient age, the interval between post-steroids and pre-HBOT, vertigo as a complication, the presence of diabetes mellitus, smoking history, and hypertension. Overall, after HBOT, complete recovery occurred in 16 (9.6%) of the patients, with definite improvement in 16 (9.6%) and slight improvement in 45 (26.9%). The overall rate of hearing improvement was higher in the study group (77/167 cases, 46.1%) than in the control group (52/160 cases, 32.5%; p = 0.021). If performed appropriately, HBOT should be able to improve hearing in many cases unresponsive to initial therapy.

Prognostic factors for idiopathic sudden sensorineural hearing loss treated with hyperbaric oxygen therapy and intravenous steroids.

OBJECTIVE This study evaluated the prognosis of idiopathic sudden sensorineural hearing loss when treated with hyperbaric oxygen therapy and intravenous steroids. METHODS The clinical data for 334 patients with idiopathic sudden sensorineural hearing loss treated by hyperbaric oxygen therapy and intravenous steroids at our hospital were retrospectively reviewed. These data included the initial averaged five-frequency hearing level, patient age, interval between onset of symptoms and treatment, vertigo as a complication, and co-existence of diabetes mellitus. RESULTS The overall improvement rate was 69.2 per cent, including better improvement (25.5 per cent), good improvement (21.0 per cent) and fair improvement (22.7 per cent). CONCLUSION Hyperbaric oxygen therapy appears to confer a significant additional therapeutic benefit when used in combination with steroid therapy for idiopathic sudden sensorineural hearing loss. If performed early, hyperbaric oxygen therapy may bring about hearing improvement in many patients who are unresponsive to initial therapy.

Undifferentiated sarcoma of the maxillary sinus: Report of a rare case in an adult

A 51-year-old man complained of left facial swelling and recurrent nasal bleeding. A giant solid tumor in the left maxillary sinus was detected on head CT and MRI, and this tumor was destroying the maxilla and extending into the orbit, pterygoid muscle and posterior paranasal sinuses. The resected specimen consisted of spindle cells containing necrotic material. Histological examination revealed immature tumor cells, and immunohistological study of the tumor showed staining was only positive for vimentin. We accordingly diagnosed undifferentiated sarcoma in the maxillary sinus. Combination chemotherapy with vincristine, doxorubicin, cyclophosphamide/ifosfamide with mesna and etoposide was administered; however, the tumor was unresponsive and the patient died after around 3 months.

Photodynamic therapy in patients with head and neck squamous cell carcinoma: PHOTODYNAMIC THERAPY FOR HEAD/NECK SCC

Photodynamic therapy (PDT) is a minimally invasive treatment for malignant tumors. The aim of this study was to determine the efficacy of PDT in patients with head and neck squamous cell carcinoma (HNSCC).

The impact of iatrogenic glottic atresia due to photodynamic therapy for laryngeal cancer: A report of two cases

Photodynamic therapy (PDT) is a minimally invasive therapy used in the treatment of premalignant and malignant diseases, including head and neck carcinomas. It can be applied before or after chemotherapy, irradiation, or surgery. Unlike irradiation and surgery, it can be repeated many times at the same site, and it is also associated with better cosmetic and functional outcomes [1]. We have treated 10 patients with laryngeal carcinomas with PDT since 1998, and herein we describe two such patients who developed vocal cord adhesion due to PDT. To our knowledge, there are no previous reports of patients with glottis atresia due to PDT, thus the cases reported herein are rare, and educationally valuable.

Hyperbaric Oxygen Therapy as Concurrent Treatment with Systemic Steroids for Idiopathic Sudden Sensorineural Hearing Loss: A Comparison of Three Different Steroid Treatments

We analyzed 356 patients with idiopathic sudden sensorineural hearing loss treated with hyperbaric oxygen therapy and systemic steroids (n = 161), systemic steroids alone (n = 160), or intratympanic and systemic steroids (n = 35). The main outcome measure was the hearing recovery rate. The effect of other variables, including the initial averaged 5-frequency hearing level, patient age, interval between the onset of symptoms and treatment, presence of vertigo as a complication, presence of diabetes mellitus, smoking history, and presence of hypertension, on the hearing recovery rate was also evaluated. The overall hearing recovery rate was significantly higher for the patients treated with hyperbaric oxygen therapy and systemic steroids than for those treated with systemic steroids alone (p < 0.001) or systemic and intratympanic steroids (p < 0.001). The presence of vertigo negatively affected hearing recovery. Our findings suggest that hyperbaric oxygen therapy confers a significant additional therapeutic benefit when used in combination with steroid therapy for idiopathic sudden sensorineural hearing loss.