A mutation at IVS1 + 5 of the von Hippel-Lindau gene resulting in intron retention in transcripts is not pathogenic in a patient with a tongue cancer?: case report.

BACKGROUND: Von Hippel-Lindau disease (VHL) is a dominantly inherited familial cancer syndrome predisposing the patient to a variety of malignant and benign neoplasms, most frequently hemangioblastoma, renal cell carcinoma, pheochromocytoma, and pancreatic tumors. VHL is caused by mutations of the VHL tumor suppressor gene on the short arm of chromosome 3, and clinical manifestations develop if both alleles are inactivated according to the two-hit hypothesis. VHL mutations are more frequent in the coding region and occur occasionally in the splicing region of the gene. Previously, we reported that the loss of heterozygosity (LOH) of the VHL gene is common in squamous cell carcinoma tissues of the tongue. CASE PRESENTATION: We describe a case of squamous cell carcinoma in the tongue caused by a point mutation in the splicing region of the VHL gene and discuss its association with VHL disease. Sequence analysis of DNA extracted from the tumor and peripheral blood of the patient with squamous cell carcinoma revealed a heterozygous germline mutation (c. 340 + 5 G > C) in the splice donor sequence in intron 1 of the VHL gene. RT-PCR analysis of the exon1/intron1 junction in RNA from tumor tissue detected an unspliced transcript. Analysis of LOH using a marker with a heterozygous mutation of nucleotides (G or C) revealed a deletion of the mutant C allele in the carcinoma tissues. CONCLUSIONS: The fifth nucleotide G of the splice donor site of the VHL gene is important for the efficiency of splicing at that site. The development of tongue cancer in this patient was not associated with VHL disease because the mutation occurred in only a single allele of the VHL gene and that allele was deleted in tumor cells.

Tongue cancer patients have a high frequency of allelic loss at the von Hippel-Lindau gene and other loci on 3p.

BACKGROUND: Although genetic abnormalities on 3p have been suggested to be linked to the development of squamous cell carcinoma of the head and neck, to the authors' knowledge no study to date has examined such genetic abnormalities in patients with squamous cell carcinoma of the tongue. In the current study, loss of heterozygosity (LOH) was evaluated at several loci within 3p, including the von Hippel-Lindau gene (VHL), in samples of tongue squamous cell carcinoma. In addition, the coding region of the intact VHL allele was screened for sequence mutations. METHODS: DNA was extracted from tumor and nontumor tissues collected from 28 patients with tongue squamous cell carcinoma. LOH was investigated by analysis of single nucleotide polymorphisms within exon 3 of VHL and by microsatellite analysis within another 10 loci. Mutation analysis of the VHL gene was performed by polymerase chain reaction (PCR) amplification and sequencing of the coding region of the gene. RESULTS: LOH within VHL was found at a high frequency (45.5%) within the tumor. However, mutations of the VHL gene were not detected in all tumor samples. LOH of other microsatellite markers on 3p was observed in 27.3% to 50% of tumor samples. Eleven (58%) of 19 samples that were informative at more than 2 loci exhibited LOH of at least 1 locus; 10 of these 11 cases exhibited LOH at multiple loci. CONCLUSIONS: A wide range of deletions in 3p, including at the VHL gene, may play a role in the development of tongue cancer.

[Long-term results of S-1 administration as adjuvant chemotherapy for advanced head and neck cancer].

The long-term results of a multi-institutional study were analyzed in 101 cases (27 with stage III and 74 with stage IV) with advanced head and neck squamous cell carcinoma (HNSCC) given S-1 administration for 6 months after definitive treatments. The 3-year disease-free survival rate was 66.3% in cases overall. In terms of the survival rates in two groups with different administration methods, i.e., 2-week administration followed by 1-week rest or 4-week administration followed by 2-week rest, there was no significant difference. The risk factors of relapse were examined by multivariate analysis. The relapse rate increased according to the advancement of N staging and the higher risk of distant metastasis in cases with laryngeal (especially, supraglottic type) or hypopharyngeal carcinomas. Now, the efficacy of S-1 administration as adjuvant chemotherapy after definitive treatments for advanced HNSCC is under investigation,and the adequate administration period of S-1 should be evaluated in a controlled randomized study in future.

Schwannoma of the retropharyngeal space.

We report a rare case of schwannoma arising from the retropharyngeal space. A 24-year-old man presented a 2-month-history of a foreign body sensation in the throat and gradually progressing dysphagia when he swallowed solids and liquids. The patient had no odynophagia, fever, or blood in his saliva. Computed tomographic scans and magnetic resonance images revealed a well-defined and oval mass, measuring about 40 mm x 20 mm in size, in the retropharyngeal space. Because the tumor existed in the retropharyngeal space and was the adequate size, the patient underwent trans-oral resection under the direct laryngoscope without the need for skin incision. On the basis of the histological findings, the tumor was diagnosed as a schwannoma. It was mostly composed of spindle cells arranged in short bundles and fascicles, with focal palisading of the nuclei. The neoplasm arising from the retropharyngeal space is quite rare, because of few anatomical structures in the space. The post-operative course was uneventful, and the patient is currently free from disease 30 months after surgery. Diagnosis, clinical behavior, and treatment of retropharyngeal schwannoma are reviewed from perusal of the literature. When schwannomas are located in the pharynx, they may cause foreign body sensation or dysphagia. Therefore, when a foreign body sensation in the larynx is present, a thorough diagnostic procedure should be performed to evaluate the morphology of the upper aerodigestive tract.

Facial nerve paralysis caused by middle ear cholesteatoma and effects of surgical intervention.

CONCLUSIONS: The clinical and surgical findings of this study indicated advanced cholesteatoma in many patients with facial paralysis. The outcome of facial paralysis was good. Poor outcomes were observed in cases with petrosal cholesteatoma and in those who underwent surgery > or = 2 months after the onset of paralysis. OBJECTIVE: To investigate clinical features of cholesteatoma associated with facial paralysis. MATERIAL AND METHODS: Sixteen patients with facial paralysis due to middle ear cholesteatoma were reviewed. After removal of the cholesteatoma lesion, a limited area of the fallopian canal, that in which facial nerve edema or redness was evident, was opened. Incision of the epineural sheath for nerve decompression was not performed. RESULTS: Initial paralysis was incomplete in 11 patients (69%). The onset of paralysis was sudden in 12 patients (75%). Labyrinthine fistulae (n = 9; 56%) and bone destruction in the cranial fossa (n = 10; 63%) were frequently observed. Six patients (38%) were totally deaf due to labyrinthitis. The outcome of facial paralysis was good in 13 patients (81%). Patients who underwent surgery > or = 2 months after the onset of paralysis frequently had a poor outcome. Paralysis was not improved in two cases with petrosal cholesteatoma.

[Concurrent chemoradiotherapy for advanced hypopharyngeal cancer].

INTRODUCTION: Chemotherapy has been shown to be most effective when delivered concurrently with radiation for the patients with advanced stage tumors. We conducted a concurrent chemoradiation using systemic infusion of cisplatin (CDDP) and 5-fluorouracil (5-FU). PATIENTS AND METHODS: Thirty-nine patients with advanced hypopharyngeal cancer received one or two cycles of intravenous administration of CDDP (80-100 mg/m2) followed by 120-hour continuous infusion of 5-FU (800-1000 mg/m2), and concomitant radiotherapy (200 cGy/day x 20-35 fractions) during the period from December, 1993 through December, 2001. Three of them were in stage III, 31 in stage IVA, and 5 in stage IVB. Until 1999 definitive surgery was planed in almost all the patients, however, primary tumors had pathologically disappeared in eleven out of the 20 (55%) of the surgical specimens. Based on the result, definitive surgery was reserved for residual or recurrent tumors afterwards. RESULTS: The complete response (CR) rates according to the T factor were 100% (1/1) for T1, 86% (6/7) for T2, 67% (2/3) for T3, and 50% (14/28) for T4, respectively. Two cycles of chemotherapy yielded a significantly higher CR rate than that of one cycle (P = 0.0371). One patient died of aspiration pneumonia. The rate of grade 3-4 leukocytopenia was 38%. The projected 5-year disease specific and overall survival rates were 57 and 51%, respectively. CONCLUSIONS: Concurrent chemoradiotherapy is promising as far as improving survival as well as organ preservation.

Laterality of human primary gustatory cortex studied by MEG.

We examined the laterality of the human gustatory neural pathway by measuring gustatory-evoked magnetic fields (GEMfs) and demonstrating the activation of the human primary gustatory cortex (PGC). In patients whose chorda tympani nerve had been severed unilaterally on the right side, we stimulated the normal side (i.e., left side) of the chorda tympani nerve with NaCl solution using a device developed for measuring GEMfs. We used the whole-head magnetoencephalography system for recording GEMfs and analyzed the frequency and latency of PGC activation in each hemisphere. "The transitional cortex between the insula and the parietal operculum" was identified as PGC with the base of the central sulcus in this experiment. Significant difference was found in frequencies among bilateral, only-ipsilateral, and only-contralateral responses by the Friedman test (P < 0.05), and more frequent bilateral responses were observed than only-ipsilateral (P < 0.05) or only-contralateral responses (P < 0.01) by the multiple comparison tests. In the bilateral responses, the averaged activation latencies of the transitional cortex between the insula and the parietal operculum were not significantly different in both hemispheres. These results suggest that unilateral gustatory stimulation will activate the transitional cortex between the insula and the parietal operculum bilaterally in humans.

[Intraarterial concomitant chemoradiation for tongue cancer: analysis of 20 patients].

Subjects were 20 patients with tongue cancer treated between April 1996 and December 2002 with intraarterial infusion of cisplatin (60-120 mg/m2) (and docetaxel 10-30 mg/m2) and intravenous infusion of sodium thiosulfate followed by 5-fluorouracil (5-FU) (800-1000 mg/m2) for 3 to 5 days. All patients underwent radiation (50-80 Gy). Ten had stage II, 4 stage III, and 6 stage IV A disease. Complete response at the primary site was achieved in 50% for T2, 67% for T3, and 0% for T4 lesions in those undergoing IA cisplatin followed by systemic 5-FU with concurrent radiation. Complete response at the primary site was achieved in all patients given IA cisplatin and docetaxel followed by systemic 5-FU with concurrent radiation. Disease-specific survival was 75% and overall survival 69% at 5 years. Side effects of treatment were tolerable, except for grade three radiomucositis in 70% of patients and grade three bone marrow depression in one treated with weekly IA chemotherapy.

Squamous papillomatosis of the bilateral nasal cavities.

The term "papillomatosis" indicates the tendency towards multicentricity and recurrence that these tumors exhibit (Snyder et al. 1972). A typical squamous papilloma arises from the nasal vestibule and is characterized by the epithelial proliferation growing an exophytic manner. We report a rare case of squamous papillomatosis of the bilateral nasal cavities. A 65-year-old man presented with a 2-year-history of bilateral nasal obstruction. Computed tomographic (CT) scans revealed a soft density mass in the bilateral nasal cavities and ethmoid sinuses. Because the tumors were limited to the nasal cavities and anterior ethmoid sinuses, total removal of the tumors was performed endoscopically. On the basis of the clinicopathological findings, the tumors were diagnosed as squamous papillomas. His post-operative course was uneventful, and he is currently free from disease 13 months after surgery. Nasal papillomas usually arise from the unilateral nasal cavity or paranasal sinus. While some cases of inverted (inverting) papillomas arising from the bilateral nasal cavities have been reported, bilateralism of the nasal squamous papillomas is quite rare. Diagnosis, clinical behavior and treatment of squamous papillomatosis of the bilateral nasal cavities are reviewed.

The role of adjustment of expiratory effort in the control of vocal intensity: clinical assessment of phonatory function.

OBJECTIVE: To determine the role of the adjustment of expiratory effort in the control of vocal intensity. STUDY DESIGN: An intensity-loading test was performed by using the airway interruption method. Three groups of subjects were used: a control group thought to resemble normal vocal fold closure, a group of patients with Reinke's edema thought to represent increased mass at the level of the vocal folds, and a group with vocal fold paralysis that was thought to represent a group with lack of adequate vocal fold closure. RESULTS: In the control group, expiratory lung pressure and airway resistance slightly increased. In the patients with Reinke's edema, expiratory lung pressure, and airway resistance significantly increased. In this group, the voice intensity was controlled by laryngeal adjustment, but a greater expiratory effort was needed because of a greater increase in glottal resistance. In the patients with vocal cord paralysis, airway resistance did not increase even with a high-intensity voice. Vocal intensity was controlled by expiratory effort. CONCLUSIONS: If there is sufficient ability for laryngeal adjustment, vocal intensity is controlled primarily by laryngeal adjustment and by expiratory adjustment in response to increased glottal resistance. However, vocal intensity is controlled by expiratory effort when laryngeal adjustment ability is poor.

A case of pleomorphic adenoma of the nasal septum.

We report a rare case of pleomorphic adenoma arising from the nasal septum. A 32-year-old woman presented with a 3-week-history of left-sided nasal obstruction. Computed tomographic scans revealed an oval mass, measuring about 30 mm in its greatest dimension, in the left anterior nasal cavity. The tumor arose from the anterior part of the nasal septum, and was removed endoscopically with endonasal approach. The microscopic finding showed a lobular and duct-like structures consisting of a loose chondromyxoid stroma. This lesion had histological characteristics of a pleomorphic adenoma, and this was confirmed by immunohistochemical expression of cytokeratin and S-100 protein. Her post-operative course was uneventful, and she is currently free from the disease 8 months after surgery. Diagnosis, clinical behavior and treatment of pleomorphic adenoma of the nasal septum are reviewed from perusal of the literature.

Phase I/II trial of weekly docetaxel and concomitant radiotherapy for squamous cell carcinoma of the head and neck.

BACKGROUND: A phase I/II trial of concurrent docetaxel and radiation for head and neck cancer was conducted to estimate the recommended dose schedule of docetaxel, and then to evaluate the therapeutic benefit. METHODS: Patients received radiation in 2.0-Gy single daily fractions to a total dose of 60 Gy. Docetaxel was administered weekly for 6 consecutive weeks. RESULTS: Docetaxel 15 mg/m(2) was considered the maximum tolerated dose (MTD). The recommended dose was decided as 10 mg/m(2). The phase II study was conducted using docetaxel at 10 mg/m(2). Thirty-nine patients were enrolled. The overall response rate was 96.9%. The prognosis of the complete response (CR) patients was significantly better than that of the partial response (PR) patients. Grade 3 or 4 adverse events consisted of lymphopenia, stomatitis, and anorexia. Thirty-two of the 35 eligible patients showed high compliance, of over 90%, and their toxicities were manageable. CONCLUSION: Even low-dose docetaxel shows a strong effect in combination with radiation, with a high survival rate in CR patients. The effect on survival will be assessed by further follow-up.A phase I/II trial of concurrent docetaxel and radiation for head and neck cancer was conducted to estimate the recommended dose schedule of docetaxel, and then to evaluate the therapeutic benefit.

[Changes in postural control mechanism after a long-time tilt].

In order to investigate the time-dependent dynamics of otolith organ-spinomotor function, we analyzed postural control biomechanically, in eight healthy adult volunteers, using a dynamic posturography (EquiTest System), before and after a four-hours lateral head and body tilt (90 degrees). After the tilt, a half of the subjects exhibited some changes. Their equilibrium scores decreased; i.e., the dependence on their vestibular inputs decreased, but in contrast, those on the visual and the somatosensory inputs increased. These changes were diminished by repeating the tests along the time course. The present findings confirmed [correction of comfirmed] the importance of vestibular gravity information for the maintenance of delicate postural stability.