Akihide Negishi

The role of whole-body FDG-PET in preoperative assessment of tumor staging in oral cancers.

Objective: The aim of this study is to clarify the clinical utility of 2-deoxy-2-[18F]fluoro-d-glucose (FDG) positron emission tomography (PET) in determining the TNM classification in patients with oral cancer.Methods: Twenty-five consecutive patients (14 male and 11 female; age range, 40 yr to 86 yr) with oral cancer were included in this study. The diagnostic accuracy for detecting cervical lymph nodes was investigated by comparing the results of CT and/or MRI and physical findings. For the semi-quantitative analysis, the tumor standardized uptake value (SUV) and tumor to background SUV ratio (T/B ratio) were assessed in primary tumors and cervical lymph nodes.Results: All primary lesions were visualized on FDG-PET images. Even though artifacts from dental materials near the lesion hampered the delineation of primary tumors on CT/MRI, the extent of primary tumors was accurately assessed by FDG-PET. The SUV and T/B ratio in the primary tumor classified in higher T grade (T3 and T4) was significantly higher than that in lower T grade (T1 and T2) (mean ± SD of SUV; 8.32±2.99 vs. 5.15±3.77, p<0.01, mean ± SD of T/B ratio; 6.96±3.23 vs. 3.61±2.76, p<0.01). The SUV and T/B ratio of metastatic lymph nodes were also significantly higher than those of normal lymph nodes (mean ± SD of SUV; 3.39±1.69 vs. 1.55±0.57, p<0.001, mean ± SD of T/B ratio; 2.46±1.08 vs. 1.03±0.22, p<0.001). Among these three methods, FDG-PET in conjunction with CT/MRI showed the highest accuracy of 92%, but there were no significant differences in diagnostic accuracy among the three methods. For the semiquantitative analysis, a threshold SUV of 2.0 provided 100% sensitivity, 82% specificity, and 88% accuracy. Furthermore, a threshold T/B ratio of 1.5 provided 100% sensitivity, 100% specificity, and 100% accuracy. Regarding the detection of distant metastasis, there was one positive result in FDG-PET showing distant pulmonary metastasis.Conclusions: Whole-body FDG-PET is an effective and convenient diagnostic tool for the evaluation of tumor staging in patients with oral cancer. Tumor staging by whole-body FDG-PET may, in fact, supplement the conventional staging by means of CT/MRI and physical findings.

Diagnosis of maxillofacial tumor withl-3-[18F]-fluoro-α-methyltyrosine (FMT) PET: a comparative study with FDG-PET

Objectives: To comparel-3-[18F]-fluoro-α-methyltyrosine (FMT)-positron emission tomography (PET) and 2-[18F]-fluoro-2-deoxy-d-glucose (FDG)-PET in the differential diagnosis of maxillofacial tumors.Methods: This study included 36 patients (16 males, 20 females; 31–90 years old) with untreated malignant tumors (34 squamous cell carcinoma, one mucoepidermoid carcinoma, one rhabdomyosarcoma) and seven patients (five males, two females; 32–81 years old) with benign lesions. In all patients, both FMT-PET and FDG-PET were performed within two weeks before biopsy or treatment of the lesions. To evaluate the diagnostic usefulness of FMT-PET and FDG-PET, visual interpretation and semiquantitative analysis were performed. PET images were rated according to the contrast of tumor uptake as compared with background, and were statistically analyzed. As a semiquantitative analysis, standardized uptake values (SUV) of the primary tumors were measured, and the SUV data were analyzed using receiver operating characteristic (ROC) curves.Results: The mean SUV of the malignant lesions were significantly higher than those of the benign lesions in both FMT-PET (2.62±1.58 vs. 1.20±0.30, p<0.01) and FDG-PET (9.17±5.06 vs. 3.14±1.34, p<0.01). A positive correlation (r=0.567, p<0.0001, n=46) was noted between FMT and FDG. ROC analysis revealed that there was no statistically significant difference in SUVs between FMT and FDG for differentiating malignant tumors. In 27 of 36 patients, FMT-PET had better contrast of malignant tumor visualization to the surrounding normal structures by visual assessment (p<0.005, binomial proportion test).Conclusions: Differential diagnosis of FMT-PET based on the uptake in maxillofacial tumors is equivalent to FDG-PET. However, the contrast of FMT uptake between maxillofacial tumors and the surrounding normal structures is higher than that of FDG, indicating the possibility of accurate diagnosis of maxillofacial tumors by FMT-PET.

Regulation of cell motility via high and low affinity autocrine motility factor (AMF) receptor in human oral squamous carcinoma cells

A tumour-secreted cytokine autocrine motility factor (AMF) induces in vivo invasion and metastasis, and in vitro tumour cell motility by a signal transduction through interaction with its cell surface receptor gp78. In this report, we investigated the characterization of a high-metastatic human oral squamous cell carcinoma (SCC) cell line LMF4 and low-metastatic HSC-3 in comparison with non-metastatic HSC-2 and HSC-4. Morphological and motility analyses revealed LMF4 cells to have the highest motile activity among those cells. However, LMF4 cells shared the similar features with HSC-3: high level secretion of AMF, enhancement of gp78 expression, co-expression of vimentin and cytokeratin, although LMF4 cells showed twice as high motile reactivity as HSC-3. The only difference was that LMF4 had twice as high amount of low-affinity receptor(s) as HSC-3, shown by Scatchard analysis.

Ultrasound-guided intralesional laser treatment of venous malformation in the oral cavity

An ultrasound-guided intralesional photocoagulation (ILP) technique using a laser is described for treatment of deep venous malformations in the oral cavity. ILP is basically a blind operation and has a risk of unintended destruction of surrounding normal tissue, therefore the authors now routinely use guidance by ultrasonography using a mini-probe to improve the safety and reliability of ILP. This approach enables safe fibre insertion, appropriate laser irradiation, and intraoperative assessment of coagulation. The use of this technique is described in 8 patients. The authors conclude that ultrasound-guided ILP with a laser is a promising technique for less-invasive treatment of a vascular malformation in the oral cavity.

Effects of Repeated Administration of Pilocarpine and Isoproterenol on Aquaporin-5 Expression in Rat Salivary Glands

Aquaporins are water channel proteins which enable rapid water movement across the plasma membrane. Aquaporin-5 (AQP5) is the major aquaporin and is expressed on the apical membrane of salivary gland acinar cells. We examined the effects of repeated administration of pilocarpine, a clinically useful stimulant for salivary fluid secretion, and isoproterenol (IPR), a stimulant for salivary protein secretion, on the abundance of AQP5 protein in rat salivary glands by immunofluorescence microscopy and semi-quantitative immunoblotting. Unexpectedly AQP5 was decreased in pilocarpine-administered salivary glands, in which fluid secretion must be highly stimulated, implying that AQP5 might not be required for fluid secretion at least in pilocarpine-administered state. The abundance of AQP5, on the other hand, was found to be significantly increased in IPR-administered submandibular and parotid glands. To address the possible mechanism of the elevation of AQP5 abundance in IPR-administered animals, changes of AQP5 level in fasting animals, in which the exocytotic events are reduced, were examined. AQP5 was found to be decreased in fasting animals as expected. These results suggested that the elevation of cAMP and/or frequent exocytotic events could increase AQP5 protein. AQP5 expression seems to be easily changed by salivary stimulants, although these changes do not always reflect the ability in salivary fluid secretion.

Immunohistochemical staining patterns of cytokeratins 13, 14, and 17 in oral epithelial dysplasia including orthokeratotic dysplasia

Diagnosis of the exact grade of oral epithelial dysplasia is difficult, and interobserver variations in grading are common. The aim of this study was to investigate the expression patterns of cytokeratins (CKs) in dysplastic oral epithelia, to identify useful double immunostaining diagnostic markers. Immunoexpression of CK13, CK14, CK17, and Ki‐67 were investigated in 21 normal epithelial specimens and 146 epithelial dysplasia specimens. In epithelial dysplasia specimens, orthokeratotic dysplasia (OKD) was identified using CK10 immunostaining. Most mild dysplasia specimens were CK13+ and CK17–. In moderate dysplasia, CK13 expression tended to be lower and CK17 expression tended to be higher than in mild dysplasia. All carcinoma in situ (CIS) specimens were CK17+. In differentiated type CIS specimens, CK13 expression was weakly positive. Most epithelial dysplasia specimens were CK14+. There were no significant differences in the expression patterns of CKs between OKD and non‐OKD specimens in any of the grades of dysplasia. These results indicate that CK14 expression can be used to detect early epithelial dysplasia, and that CK13 and CK17 expression are useful for detecting neoplastic changes.

Synergistic effect of heat shock protein 90 inhibitor, 17-allylamino-17- demethoxygeldanamycin and X-rays, but not carbon-ion beams, on lethality in human oral squamous cell carcinoma cells

The purpose of this study is to clarify the effect of a heat shock protein 90 inhibitor, 17-allylamino-17-demethoxygeldanamycin (17-AAG), in combination with X-rays or carbon-ion beams on cell killing in human oral squamous cell carcinoma LMF4 cells. Cell survival was measured by colony formation assay. Cell-cycle distribution was analyzed by flow cytometry. Expression of DNA repair-related proteins was investigated by western blotting. The results showed 17-AAG to have synergistic effects on cell lethality with X-rays, but not with carbon-ion beams. The 17-AAG decreased G2/M arrest induced by X-rays, but not by carbon-ion beams. Both X-ray and carbon-ion irradiation up-regulated expression of non-homologous end-joining-associated proteins, Ku70 and Ku80, but 17-AAG inhibited only X-ray-induced up-regulation of these proteins. These results show that 17-AAG with X-rays releases G2/M phase arrest; cells carrying misrepaired DNA damage then move on to the G1 phase. We demonstrate, for the first time, that the radiosensitization effect of 17-AAG is not seen with carbon-ion beams because 17-AAG does not affect these changes.

Homozygous deletions on the short arm of chromosome 3 in human oral squamous cell carcinomas

Recent cytogenetic and allelic deletion analyses have demonstrated that deletions on the short arm of chromosome 3 (3p) are frequently found in various cancers, including oral squamous cell carcinomas (OSCCs). This suggests that one or more tumor suppressor gene(s) for these malignancies might be located on 3p. In the present study, to further define the region(s) on 3p that harbor putative tumor suppressor gene(s) for OSCCs, we have investigated the existence of homozygous deletions (HDs) at 34 loci on 3p, in 14 OSCC cell lines. HDs were detected within the FRA3B region at 3p14.2 in only two cell lines (HSC-4 and TSU). Recently, the human fragile histidine triad (FHIT) gene was isolated from this region, abnormalities of which have been found at high frequencies in several types of human cancers. We also examined the expression of the FHIT gene, using reverse transcription-polymerase chain reaction (RT-PCR) and exon-specific PCR, in the two OSCC cell lines which showed HDs at 3p14.2. There was no detectable expression of exon 5, which was the first protein-coding exon of FHIT gene, in HSC-4 cells, indicating that this region was homozygously deleted in this cell line. On the other hand, HD in the TSU cells did not affect the coding region of the FHIT gene, and the wild-type transcript was detected by RT-PCR. Therefore, several candidate tumor suppressor genes, including the FHIT gene, may reside in these homozygously deleted regions. To our knowledge, this is the first report of HDs on 3p in OSCCs.

Bizarre parosteal osteochondromatous proliferation of the maxilla: a case report

Bizarre parosteal osteochondromatous proliferation (BPOP) is a rare benign lesion of bone, known as Noras lesion. The lesion often behaves like a malignant tumor, clinically and microscopically. BPOP usually occurs in the small tubular bones of the hands and feet, and a lesion arising in the oral and maxillofacial region is extremely rare. In this report, we present a case of BPOP arising in the maxilla of an adult woman, in the absence of trauma. After the initial lesion was excised, the patient began orthodontic treatment. The lesion recurred twice, both times appearing in almost the same location. Finally, the lesion was excised via marginal resection of the maxilla. In this case, it is suspected that the orthodontic treatment may have affected the recurrence of BPOP, because there was no history of trauma.

Postoperative evaluation of the folded pharyngeal flap operation for cleft palate patients with velopharyngeal insufficiency.

Background: Velopharyngeal function is very important for patients with cleft palate to acquire good speech. For patients with velopharyngeal insufficiency, prosthetic speech appliances and speech therapy are applied first, and then pharyngeal flap surgery to improve velopharyngeal function is performed in our hospital. The folded pharyngeal flap operation was first reported by Isshiki and Morimoto in 1975. We usually use a modification of the original method. Purpose: The purpose of this research was to introduce our method of the folded pharyngeal flap operation and report the results. Materials and Methods: The folded pharyngeal flap operation was performed for 110 patients with velopharyngeal insufficiency from 1982 to 2010. Of these, the 97 whose postoperative speech function was evaluated are reported. The cases included 61 males and 36 females, ranging in age from 7 to 50 years. The time from surgery to speech assessment ranged from 5 months to 6 years. In order to evaluate preoperative velopharyngeal function, assessment of speech by a trained speech pathologist, nasopharyngoscopy, and cephalometric radiography with contrast media were performed before surgery, and then the appropriate surgery was selected and performed. Postoperative velopharyngeal function was assessed by a trained speech pathologist. Results: Of the 97 patients who underwent the folded pharyngeal flap operation, 85 (87.6%) showed velopharyngeal competence, 8 (8.2%) showed marginal velopharyngeal incompetence, and only 2 (2.1%) showed velopharyngeal incompetence; in 2 cases (2.1%), hyponasality was present. Approximately 95% of patients showed improved velopharyngeal function. Conclusions: The folded pharyngeal flap operation based on appropriate preoperative assessment has been shown to be an effective method for the treatment of cleft palate patients with velopharyngeal insufficiency.