Epigenetic inactivation of galanin receptors in salivary duct carcinoma of the parotid gland: Potential utility as biomarkers for prognosis.

Salivary duct carcinoma (SDC) constitutes one of the most aggressive cancers in the salivary gland and is associated with a poor prognosis; however, no established systemic therapy options are available. SDC exhibits biological similarity to prostate and breast cancers, therefore anti-hormone therapy and molecular target therapies are available, however with limited beneficial effects. Galanin and galanin receptors (GALRs) are well established as molecular biomarkers to predict the survival rate and risk of recurrence of head and neck squamous cell carcinoma. The present study investigated the clinicopathological features of patients with SDC and the methylation status of their galanin and GALR genes to demonstrate the prognostic value for this disease. The median overall survival (OS) was 37.2 months. T-stage, N-stage, disease stage, tumor size, and preoperative facial paralysis were significantly associated with OS, whereas human epidermal growth factor receptor 2 (HER2) overexpression was not. GALR1 and GALR2 methylation rates in tumor tissues were significantly increased compared with normal tissues with 9.85- and 4.49-fold increase, respectively. p27kip1 and p57kip2 expression significantly inversely correlated with the methylation rate of GALR1 and GALR2. In addition, the observed GALR1 and/or GALR2 methylation rates were significantly correlated with a decrease in OS. These results suggest that GALR1 and GALR2 may serve as potential prognostic factors and therapeutic targets in SDC.

Safety and short-term outcomes of basic fibroblast growth factor injection for sulcus vocalis.

BACKGROUND: Sulcus vocalis (SV) is characterized by the appearance of a groove and fibrotic changes in the vocal fold mucosa and an often irrevocable loss of tissue viscoelasticity and vibratory potential. Although several surgical approaches have been proposed, none are ideal treatments. Basic fibroblast growth factor (bFGF) may stimulate fibroblasts in the superficial layer of the lamina propria (SLP) and increase the vibration of vocal fold mucosa. AIMS/OBJECTIVES: The aim of this study was to evaluate the safety and short-term outcomes of bFGF injection for SV. MATERIALS AND METHODS: This study was registered with the University Hospital Medical Information Network-Clinical Trials Registry (UMIN000019347). Twelve cases of pathological SV were treated using a method involving bFGF injection. The treatment regimen involved the injection of 50 µg of bFGF into the SLP. More than 3 months after the injection, aerodynamic and acoustic outcomes were examined. RESULTS: No adverse events were recorded. Significant improvements were observed in the maximum phonation time (MPT) and Voice Handicap Index (VHI) after treatment. Multiple injections achieved additional effects. CONCLUSIONS AND SIGNIFICANCE: bFGF injection may be a safe and suitable office-based surgery for the alleviation of hoarseness caused by SV based on this preliminary short-term study.

Topical application of timolol decreases the severity and frequency of epistaxis in patients who have previously undergone nasal dermoplasty for hereditary hemorrhagic telangiectasia.

OBJECTIVE: Hereditary hemorrhagic telangiectasia (HHT) is widely known to cause bleeding that is difficult to control because of the associated vascular wall fragility. Although nasal dermoplasty results in decreased severity and frequency of nasal bleeding in patients with HHT, it does not eradicate epistaxis because this procedure cannot cover the entire nasal cavity. Residual bleeding warrants additional effective therapy. Preliminary reports on the use of ß-adrenergic blockers for treating epistaxis in patients with HHT encouraged us to examine their effects in HHT patients who had previously undergone nasal dermoplasty but still complained of epistaxis. METHODS: We performed a prospective topical timolol, a nonselective beta blocker, application study involving 12 HHT patients who had undergone nasal dermoplasty. The observation period lasted for 3 months. RESULTS: There was one improperly enrolled case in which timolol administration was discontinued. The mean score of bleeding intensity and that of bleeding frequency were markedly reduced after treatment. Two patients who had required transfusions before treatment did not need them afterward, and patients were generally satisfied with the treatment. CONCLUSION: Topical timolol application was effective in decreasing epistaxis. Although no adverse effects were observed in the properly selected patients, there are contraindications to timolol application that should be kept in mind when applying this treatment.

Three cases of organized hematoma of the maxillary sinus: clinical features and immunohistological studies for vascular endothelial growth factor and vascular endothelial growth factor receptor 2 expressions.

Objectives. Organized hematoma (OH) is a rare, nonneoplastic, hemorrhagic lesion causing mucosal swelling and bone thinning, mainly in the maxillary sinus. We aimed to clarify the clinical presentation and treatment of OH. Methods. Three cases of maxillary sinus OH and a literature review are presented. Results. Three men aged 16-40 years complained of nasal obstruction, frequent epistaxis, and/or headache. Clinical and radiological examinations revealed a maxillary sinus OH. They were cured in a piecemeal fashion via endoscopic middle meatal antrostomy. Furthermore, vascular endothelial growth factor and its receptor were expressed in the lesion. Conclusions. The pathogenesis of OH is unclear and it presents various histological and imaging findings; however, it is not difficult to rule out malignant tumors. Minimally invasive surgery such as endoscopic sinus surgery can cure it completely. Thus, it is important to determine the diagnosis using CT and MRI and to quickly provide surgical treatment.

Rare case of malignant transformation of recurrent respiratory papillomatosis associated with human papillomavirus type 6 infection and p53 overexpression.

Recurrent respiratory papillomatosis (RRP), a chronic upper respiratory condition characterized by diffuse multiple recurring papillomas, is thought to result from human papillomavirus (HPV) type 6 or 11 infection. Although RRP is an intractable disease, malignant transformation of RRP is rare. The underlying mechanism, however, has not been elucidated. We describe the clinical course of a patient who underwent more than 130 operations for RRP associated with HPV type 6 infection and subsequently suffered spontaneous malignant transformation to squamous cell carcinoma. Immunohistochemical analysis revealed that malignant transformation might result from a genomic defect, such as p53 inactivation, leading to stimulation of uncontrolled cell proliferation by HPV type 6 for an extended period, but not directly because of HPV itself. Our results could help in the development of novel therapeutic strategies for severe RRP, although further studies are required before clinical application of molecular targeted therapies.

[Clinical 22-case study of hereditary hemorrhagic telangiectasia subjects undergoing nasal dermoplasty].

Hereditary hemorrhagic telangiectasia (HHT)-a systemic autosomal dominant disorder adversely affecting skin, mucous membranes, and visceral blood vessels-typically shows epistaxis. In this pathological condition, even minor stimulation may cause bleeding and hemostasis is unlikely to occur. Subjects with HHT showing severe nasal bleeding require nasal dermoplasty (ND). We report our experience in 22 cases of HHT undergoing ND seen from January 2000 to November 2009. Average age at surgery was 55.8 years. Since April 2008, we modified ND, cut the harvested skin graft from the lateral thigh in halves and spread each strip on the anterior halves of the nasal cavity. Placement was circumferential in the sequence of agger nasi, nasal valve, septum, floor, and inferior turbinate. Before this technique was used, bleeding could not be controlled in 3 of 14 cases. Two of the 3 had histories of arterial embolization. Subjects undergoing the new technique have enjoyed improved quality of life.

Cytokine profiles in Japanese patients with chronic rhinosinusitis.

BACKGROUND: Chronic rhinosinusitis (CRS) is classified in CRS without nasal polyp (CRSsNP) and CRS with nasal polyp (CRSwNP) in western countries, whereas this classification was not common so far in Japan. Studying inflammatory mediators in clearly defined disease subgroups may lead to a better differentiation of chronic sinus diseases. METHODS: Homogenates of sinonasal mucosal tissue from 14 controls, 9 CRSsNP patients, and 19 CRSwNP patients were assayed for transforming growth factor (TGF)-ß, interleukin (IL)-5, immunoglobulin E (IgE), Staphylococcus enterotoxin (SAE)-IgE, eosinophil-catioic protein (ECP), myeloperoxidase (MPO), IL-1ß, IL-6, and IL-8 by enzyme-linked immunosorbent assay or UNICAP system. RESULTS: CRSwNP had significantly higher levels of IL-5, IgE, SAE-IgE, and ECP compared with CRSsNP and controls. CRSsNP was characterized by high levels of TGF-ß, while CRSwNP showed a Th2 polarization and lower levels of TGF-ß. Especially, in CRSwNP samples, 68.4% were eosinophilic (ECP/MPO ratio >1), and 52.6% were SAE-IgE positive. On the other hand, in 9 CRSsNP patients, eosinophilic or SAE-IgE positive sample was only one sample respectively. Additionally, 31.6% of CRSwNP were asthmatic patients, while none of CRSsNP patient was suffering from bronchial asthma. CONCLUSIONS: This study is thought to be the first one that showed the cytokine profiles in Japanese CRSs/wNP similar to those of European CRS. Based on mediator profiles, we suggest that CRSsNP and CRSwNP are distinct disease entities within the group of chronic sinus diseases.

Are patients with severe epistaxis caused by hereditary hemorrhagic telangiectasia satisfied with nostril closure surgery?

OBJECTIVE: Recurrent epistaxis as a manifestation of hereditary hemorrhagic telangiectasia (HHT) is usually difficult to control. Although no treatment is regarded to be completely efficacious, nostril closure is considered a modality of choice for the most severe cases. The cessation of airflow resulting from this procedure can stop bleeding by minimizing risk factors. However, loss of nasal functions is a disadvantage of nostril closure. We conducted a questionnaire survey of patients who underwent nostril closure surgery, regarding the effects and disadvantages of the operation. METHODS: Seven patients were asked questions on issues including frequency and severity of epistaxis pre- and post-operatively, satisfaction of treatment, and impairment in daily living activities. RESULTS: Most patients reported complete cessation of bleeding. Some still had bleeding, but the frequency and severity were far lower. No transfusions were required in any of the cases. Patients reported some disadvantages, for example, respiratory, olfactory, and phonatory issues. Six out of seven patients were very satisfied with the outcome of surgery. CONCLUSION: Nostril closure surgery can remarkably reduce frequency and volume of epistaxis. Our survey indicated that satisfactory results were achieved. However, difficulties caused by complete nasal obstruction varied. Thus, individualized coping strategies are required.

A new method of nasal dermoplasty (MW grafting method) in patients with large septal perforation.

Nasal dermoplasty is effective in controlling epistaxis in patients with hereditary hemorrhagic telangiectasia (HHT). Skin graft take failure occurs mostly in cases of large septal perforation. The MW method was developed as a modification of nasal dermoplasty designed for patients with HHT having a large septal perforation. It seems to be a safe and effective approach and should be tried for recurrent bleeders with septal perforation.

Experimentally induced eosinophilic polyps in rabbit sinuses.

BACKGROUND: Nasal polyps are one of the most common findings of physical examination in the otolaryngology area and the experimental model of nasal polyps in the rabbit maxillary sinus is helpful for clarifying the mechanism of polyp formation. Several protocols have been reported for this model, but most of them involved infectious polyps without eosinophil infiltration. We have attempted to establish a novel rabbit model of polyps associated with eosinophil infiltration. METHODS: Rabbits were either untreated (group A) or sensitized with ovalbumin (OVA; groups B-D). After repeated exposure to OVA, some animals further received valine-glycine-serine-glutamine (group C) or poly-L-arginine (group D) in their maxillary sinuses for 4 weeks. Subsequently, sinus tissues were dissected and subjected to histological analysis. The changes in mRNA expression were analyzed by DNA microarray. RESULTS: Remarkable histological changes were observed in groups C and D but not in group B in eosinophil number in the maxillary sinus mucosa, the width of the lamina propria, and polyp scoring. These changes in group D were greater than those in group C. DNA microarray analysis revealed that up-regulated genes in group D included those related to inflammation and extracellular matrix metabolism. On the other hand, down-regulated genes in group D involved those related to anti-inflammation. CONCLUSION: Our results indicate that treatment with inflammatory agents, in combination with an antigen-dependent immune response, could induce nasal polyp formation associated with eosinophil infiltration and mucosal hypertrophy. The gene expression profile supported the clinical relevance of this model.