Takeshi Asakawa

Efficacy of multidrug superselective intra-arterial chemotherapy (docetaxel, cisplatin, and 5-fluorouracil) using the Seldinger technique for tongue cancer

Abstract Conclusion: This therapy produced better results than intravenous multidrug chemotherapy (CF therapy, CPF therapy, etc.) or superselective intra-arterial chemotherapy (SIC) alone with cisplatin (CDDP) and 5-fluorouracil (5-FU). Primary tumor may be controlled by SIC alone in cases of T2 and many cases of T3 tumors, and by the combination of SIC and concurrent radiotherapy in cases of T3 and many cases of T4a. Cervical lymph node metastasis was treated with neck dissection in some patients. The results indicate that this therapy is useful to control primary tumor without resection for organ preservation. Objectives: This therapy was intended to control primary tumor without resection for better quality of life (QOL). Methods: A total of 45 patients with primary squamous cell carcinoma of the tongue were included in the study. SIC with docetaxel, cisplatin, and 5-FU was administered. Results: In terms of the primary response of primary tumor, 43 patients achieved a clinical complete response (CR). Moreover, in these patients no cancer cells were histopathologically found by biopsy, resulting in a response rate of 100% and a CR rate of 95.6%. During the median follow-up period of 1779 days (59 months) (range 110–3752 days), the 5-year survival rate and organ preservation rate were 89.8% and 80.7%, respectively.

Cervical branch of the facial nerve approach for retrograde parotidectomy compared with anterograde parotidectomy

Abstract Conclusion: The cervical branch of the facial nerve approach for parotidectomy is an excellent surgical technique that can reduce the incidence of facial nerve paralysis, surgical time, and surgical blood loss. Objective: To develop and evaluate a surgical technique for parotidectomy that can reduce the incidence of facial nerve paralysis. Methods: Retrograde parotidectomy following identification of the cervical branch of the facial nerve in 90 subjects was compared with standard anterograde parotidectomy in 100 subjects. Results: Retrograde parotidectomy with a cervical branch approach was associated with significant decreases in the incidence of facial nerve paralysis, surgical time, and surgical blood loss, compared with anterograde parotidectomy.

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

BackgroundVon 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 PresentationWe 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.ConclusionsThe 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.

Expression of von Hippel–Lindau tumor suppressor protein (pVHL) characteristic of tongue cancer and proliferative lesions in tongue epithelium

BackgroundPatients with tongue cancer frequently show loss of heterozygosity (LOH) of the von Hippel–Lindau (VHL) tumor suppressor gene. However, expression of VHL protein (pVHL) in tongue cancer has rarely been investigated and remains largely unknown. We performed immunohistochemical staining of pVHL in tongue tissues and dysplasia, and examined the association with LOH and its clinical significance.MethodsImmunohistochemical staining of pVHL in formalin-fixed, paraffin-embedded sections of cancerous and other tissues from 19 tongue cancer patients showed positivity for LOH of VHL in four samples, negativity in four samples, and was non-informative in 11 samples. The staining pattern of pVHL was also compared with those of cytokeratin (CK) 13 and CK17.ResultsIn normal tongue tissues, pVHL staining was localized to the cytoplasm of cells in the basal layer and the area of the spinous layer adjacent to the basal layer of stratified squamous epithelium. Positive staining for pVHL was observed in the cytoplasm of cancer cells from all 19 tongue cancer patients. No differences as a result of the presence or absence of LOH were found. Notably, cytoplasm of poorly differentiated invasive cancer cells was less intensely stained than that of well and moderately differentiated invasive cancer cells. pVHL staining was also evident in epithelial dysplasia lesions with pVHL-positive cells expanding from the basal layer to the middle of the spinous layer. However, no CK13 staining was noted in regions of the epithelium, which were positive for pVHL. In contrast, regions with positive staining for CK17 closely coincided with those positive for pVHL.ConclusionsPositive staining for pVHL was observed in cancerous areas but not in normal tissues. pVHL expression was also detected in lesions of epithelial dysplasia. These findings suggest that pVHL may be a useful marker for proliferative lesions.

A new combined therapy for functional organ preservation and survival in lateral oropharyngeal wall cancer

Abstract Conclusion: The outcome of this treatment was good, indicating that it is safe and effective. A favorable outcome was obtained, especially in patients with T3, N0–1, and N2a–b cancer, while outcome remained unfavorable in patients with T4a and N2c cancer. Consideration should be given to the need for intensity-modulated radiation therapy (IMRT) and maintenance therapy. Objective: To improve the survival and functional organ preservation rates in patients with lateral oropharyngeal squamous cell carcinoma. Methods: The primary site was treated conservatively by neoadjuvant chemotherapy and/or concurrent chemoradiation therapy. Chemotherapy was administered by superselective intra-arterial infusion and cervical lymph node metastasis was treated by radical neck dissection. Results: Among 71 patients, the 5- and 10-year overall survival rates were 85.1% and 63.5%, respectively; and the 5- and 10-year functional organ preservation rates were 61.0% and 51.6%, respectively. The outcomes were especially good in patients with T3 N0–1, and N2a–b cancer. All patients with N2c cancer had poor outcomes.