[in Japanese]

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Olfactory neuroblastoma is an uncommon intranasal tumor originating from olfactory neuroepithelium. Despite the development of electron microscopy and immunohistochemical testing, the pathological diagnosis of this tumor is still difficult because of the wide range of histological features. Magnetic resonance imaging (MR) of this tumor and the pattern of contrast enhancement have not been well described.
The purpose of this report was to analyze the MR characteristics of olfactory neuroblastomas. The MR signal, pattern of contrast enhancement, and correlation with high-resolution computed tomography (CT) imaging were examined.
Seventeen patients with olfactory neuroblastoma were treated at Hokkaido University Hospital and a related hospital during the past 25 years. MR images taken in 12 patients and CT images taken in 9 patients with histologically confirmed olfactory neuroblastoma were retrospectively reviewed.
Compared with brain gray matter, 11 tumors were hypointense on T1-weighted images, 9 homogeneously and 2 heterogenously. Eight tumors were hyperintense on T2-weighted images, 3 homogeneously and 5 heterogeneously, although their appearance was less intense than that of sinusitis. Gadolinium enhancement was moderate in one case and marked in 10 of the 11 cases, 9 homogeneously and 2 heterogeneously. Nine of the 11 tumors showed smooth regular shaped margins; 2 of these tumors exhibited irregular infiltrating margins on gadolinium-enhanced images, compared to the pre-contrast T1-weighted images. Eight of the 11 tumors had clearly demarcated margins, while 3 of the 11 tumors did not exhibit gadolinium enhancement. Six of the 12 cases (50%) exhibited intracranial cysts on the gadolinium-enhanced images. T2-weighted or gadolinium-enhanced images successfully distinguished sinusitis from tumors in 4 cases whereas the CT images failed. Gadolinium enhancement, particularly in the tangential plane, demonstrated intracranial extension not apparent on the CT images in one case.
In most cases, olfactory neuroblastomas are hypointense on T1-weighted images, hyperintense on T2-weighted images, and show marked homogeneous enhancement with well-demarcated regular margins upon gadolinium enhancement. Although the definite diagnosis is based on histopathology findings and MR features are nonspecific, they may suggest an imaging diagnosis of olfactory neuroblastoma when seen in the superior nasal cavity. MR is superior to CT both in delineating the extent of the tumor and in making an imaging diagnosis.

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To evaluate the efficacy of adjuvant chemotherapy after concurrent chemoradiotherapy, 41 previously untreated patients with locally advanced and resectable head and neck squamous cancer were enrolled in a study to compare adjuvant chemotherapy (Nedaplatin/UFT) after concurrent chemoradiotherapy (CDDP/5-FU) and concurrent chemoradiation alone. Nine of the patients had stage III tumors and 32 had stage IV tumors. The primary tumor site was the hypopharynx in 14 patients, the larynx in 12 patients, the oral cavity in 9 patients, and the oropharynx in 6 patients. Treatment consisted of 6 courses of Nedaplatin (80mg/m²) repeated at 4-week intervals and one year of the oral administration of UFTE (400mg/day) after concurrent chemoradiotherapy at an outpatient clinic. Toxicities included leukopenia (grade 3, 15.4%) and thrombocytopenia (grade 3, 7.7%). One death from a gastric ulcer occurred. The median overall survival time was 30.1 months (5.5-50.1 months) for the adjuvant chemotherapy group and 21.7 months (4.0-48.8 months) for the control group. The progression-free survival period was 22.8 months (5.6-33.9 months) for the adjuvant chemotherapy group and 26.5 months (5.6-33.9 months) for the control group. The two-year overall survival rate was 73.3% for the adjuvant chemotherapy group and 55.7% for the control group. A significant difference was observed in the two-year progression-free survival rates: 66.9% for the adjuvant chemotherapy group and 27.8% for the control group (p=0.03290). Among the patients with a partial response to concurrent chemoradiotherapy, in particular, a significant difference in the two-year progression-free survival rates was seen: 59.3% for the adjuvant chemotherapy group and 15.3% for the control group (p=0.01102). The rate of loco-regional failure was 29.6% for the adjuvant chemotherapy group and 64.3% for the control group (p=0.0716). Distant metastasis was not detected in either group. The rate of organ preservation was 66.7% for the adjuvant chemotherapy group and 35.7% for the control group (p=0.1183). This adjuvant chemotherapy regimen might improve-the loco-regional control rates after concurrent chemoradiotherapy.

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Chronic sinusitis with eosinophils easily recurs after endoscopic sinus surgery. The condition is usually complicated by asthma, and many eosinophils are present in the sinus mucosa. One conservative treatment method is the administration of glucocorticoids locally or systematically. To evaluate the efficacy and tolerability of intranasal fluticasone propionate for the treatment of chronic sinusitis with eosinophils, seven patients with chronic sinusitis with eosinophils were treated over a 12-week period using a fluticasone propionate aqueous nasal spray (800μg per day in each nostrilz). The Symptons of 7 patients, especially nasal discharge and nasal obstructions, improved and an expanded air space was observed on paranasal CT images. The percent of drug systemically available after intranasal administration varied by less than 1% for intranasal fluticasone propionate. Therefore, even if intranasal fluticasone propionate is administerved at double the usual dose, it is unlikely to cause systemic side effects. Fluticasone propionate aqueous nasal spray at double the usual dose is effective for the treatment of chronic sinusitis with eosinophils.

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Purpose: Metastatic activity is one parameter indicating the malignancy of tumor cells. Angiogenesis has now been extensively studied to clarify the mechanisms of tumor growth and metastasis. Vascular endothelial growth factor (VEGF) is an angiogenic cytokine expressed by many human and animal tumors. We studied the role of VEGF in tumor growth by transfecting the VEGF gene into tumor cells and analyzing the survival period of nude mice implanted with these transfected tumor cells.
Materials and Methods:
Cell line: The tumor cell line, OKK-LN, was established from human maxillary squamous cell carcinoma and used in this study. The tumor cells did not produce VEGF in the culture supernatant.
Transfection: OKK-LN cells were stably transfected with sense VEGF165 cDNA or with the vector alone. The full-length VEGF165 cDNA was cloned into an expression vector (pCIneo). The DNA transfection was performed by the lipofection method, and the limiting dilution method was used for cloning. ELISA was used to measure VEGF in the culture supernatant. As a control, OKK-LN cells were transfected with the vector alone without VEGF (OKK-LN/pCIneo). The tumor cells were subcutaneously injected into nude mice (Balb/c nu/nu, 6W), and the survival period and tumor volume were analyzed.
Effects of angio-suppressive agent, TNP-470, and anti-VEGF antibody on tumor growth and angiogenesis: TNP-470 (supplied by Takeda Pharmaceutical Co., Ltd.) and monoclonal anti-human VEGF antibodies were intraperitoneally administered to mice implanted with tumor cells once a week and twice a week for 5 weeks, respectively. The effects of TNP-470 and anti-VEGF antibodies were analyzed by examining tumor size and survival rate and immunohistologically using CD31 monoclonal antibody.
Results: Tumor cells transfected with sense VEGF 165 cDNA (referred to as OKK-LN/pCIneo-VEGF ) produced VEGF in the supernatant permanently, confirming the establishment of a VEGF-producing human cancer cell line. We observed marked tumor growth and a shortened survival period by nine days in the OKK-LN/pCIneo-VEGF group, compared to the control group. The administration of TNP-470 and anti-VEGF antibody significantly suppressed tumor growth. The immunohistological study showed the significant suppression of a number of tumor vessels in anti-VEGF antibody-administered mice.
Conclusion: Our data strongly suggests that VEGF plays an important role in tumor growth and that treatment by anti-VEGF antibody may be a promising strategy against head and neck cancers.

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