Determination of matrix metalloproteinase 9 (MMP-9) protein expression in laryngeal squamous cell carcinomas based on digital image analysis.

PURPOSE: Matrix metalloproteinases (MMPs) is a superfamily of proteins involved in angiogenesis and metastatic tissue invasion in many cancers. Overexpression of MMP- 9 has been detected in significant proportions of laryngeal squamous cell carcinomas (LSCCs), but its prognostic impact remains unclear. In this study we performed a digital image analysis for analyzing MMP-9 protein expression in a series of LSCCs correlating them with clinicopathological factors. METHODS: MMP-9 protein expression level was determined immunohistochemically in 30 tissue sections surgically derived from patients (21 male and 9 female) with LSCC. Using digital image analysis, we measured their corresponding protein expression levels (staining intensity/S.I. range values 0-255). RESULTS: Moderate and high MMP-9 protein expression levels (grouping as 2+/3+ overexpression) were detected in 19/30 (63.3%) cases. Statistical significance was observed correlating stage with SI (p=0.02), whereas a borderline association with differentiation grade of the examined tumors was also registered (p=0.05). Interestingly, high levels of MMP-9 expression were observed in cases that demonstrated a significant level of inflammatory (predominantly lymphocytic) infiltration. CONCLUSION: MMP-9 protein overactivation is a frequent and significant genetic event in LSCC, correlating with its biological behavior (increased TNM stage). MMP-9 seems to mediate an epithelial-stromal intra-reaction correlating also with induction of specific inflammation pathways.

MIF attenuates the suppressive effect of dexamethasone on IL-6 production by nasal polyp.

BACKGROUND: Nasal polyposis (NP) is a chronic inflammatory disease of the upper airways, that characterized by inflammatory cells infiltration, extracellular matrix accumulation and oedema. Interleukin-6 (IL-6) is a multifunctional cytokine, implicated in various inflammatory conditions, including NP pathogenesis. Macrophage migration inhibitory factor (MIF) is a pro-inflammatory mediator able to antagonize the inhibitory effects of glucocorticoids on the expression of various cytokines and growth factors. AIM: To investigate the presence of MIF in nasal polyp tissues and the influence of a MIF activity inhibitor on dexamethasone effects on IL-6 production. PATIENTS AND METHODS: Nasal polyps were resected by functional endoscopic sinus surgery for treatment of chronic sinusitis with polyposis and healthy nasal mucosa was taken during nasal septoplasty-chochoplasty. MIF and IL-6 levels were determined by ELISA. The expression of MIF and IL-6 at the mRNA level was ascertained by RT-PCR. RESULTS: MIF was detected in all polyp tissue extracts and tissue cultures conditioned media. MIF and IL-6 expression were significantly higher in polyp tissues as compared to normal nasal mucosa tissues. Dexamethasone at concentration 1-100 microM caused a statistically significant dose-dependent suppression of IL-6 production by polyp tissue cultures. Inhibition of MIF by (S,R)-3-(4-hydroxyphenyl)-4,5-dihydro-5-isoxazole acetic acid methyl ester (ISO-1), an inhibitor of MIF tautomerase activity, significantly enhanced the dexamethasone suppressive effect on IL-6 production. CONCLUSIONS: MIF, presence in polyp tissue, attenuates the suppressive effect of dexamethasone on the production of IL-6 by this tissue, since the simultaneous use of its inhibitor ISO-1 leads to an enhancement of dexamethasone activity. Therefore, it is reasonable to propose that the utilization of MIF inhibitors together with glucocorticoids in clinical practice may be beneficial in the treatment of NP.

Presence of hyaluronidase isoforms in nasal polyps.

BACKGROUND: Nasal polyps are benign lesions originating from the nasal mucosa or paranasal sinuses. The most important etiological factor seems to be increased hydration of epithelium and hyperplasia of the extracellular matrix, which may involve hyaluronan, a high molecular mass extracellular glycosaminoglycan. Degradation of hyaluronan proceeds through the action of specific hyaluronidases. OBJECTIVE: The aim of the present study was to investigate the hydrodynamic size of hyaluronan and the presence of the various hyaluronidase isoforms in nasal polyps. METHODS: Samples of polypoid mucosal tissue and normal nasal mucosa were obtained from twenty patients suffering from nasal polyposis. Zymographic analysis and western blotting were used to detect hyaluronidase activity. RESULTS: The results indicated the presence of hyaluronan of small molecular mass in all samples examined. About one third of it has a mean molecular mass of 240 kDa, exactly that required for the expression of inflammatory response. Laboratory analysis suggested that degradation of hyaluronan occurred through the action of three hyaluronidase isoforms: Hyal-1, Hyal-2 and PH-20. CONCLUSIONS: Since hyaluronan fragments of 200-250 kDa induce the expression of inflammatory cytokines, a specific role of hyaluronidases in the development or progression of nasal polyps may be concluded. Therefore, new treatment protocols may be proposed.

Factors influencing quality of life after total laryngectomy: a study of 92 patients.

BACKGROUND AND OBJECTIVES: Total laryngectomy is a radical surgery for advanced laryngeal cancer. In the present study we evaluate the influencing factors for long term quality of life of 92 laryngectomees. PATIENTS AND METHODS: 92 patients who underwent laryngectomy for laryngeal cancer in the University Hospital of Patras, Greece were evaluated using a modified version of the EORTC-QOL-C30 questionnaire. The patients were distributed into 6 groups based on time elapsed between surgical treatment and completion of the questionnaire, ranging from 2 years for group 1 to 9-10 years for group 6. RESULTS: The mean value of psychological status (p=0.01), smelling disorders (p=0.032), mood change (p=0.003) were statistically significant in regard to the patient's overall view of their life postsurgically. Coexisting illness (defined as diabetes, hypertension or prostate disease which required medication on daily basis or hospitalization more than two times a year) was also significantly affecting (p=0.021) the patient's oral communication skills. CONCLUSION: Quality of life is affected by functional disabilities and the psychological state of the patients. No statistically significant improvement over time was noted in our series.

Necrotizing fasciitis of the head and neck: report of 5 cases and review of the literature.

BACKGROUND: Necrotizing fasciitis (NF) is a severe, rapidly spreading soft tissue infection of polymicrobial origin. This condition most frequently affects thorax, abdominal wall, extremities, perineum and groin, but according to recent literature the head and neck area is also involved with increasing frequency. PATIENTS AND METHODS: Five cases of head and neck NF were detected among patients who were admitted at the Department of Otorhinolaryngology-Head and Neck Surgery of the University Hospital of Patras, Patras, Greece, over a 5-years period. Various parameters including patients' health status, co-morbidity, etiology, microbiology, affected area, antibiotic therapy, hospital stay, surgical treatment and complications were considered. CONCLUSIONS: The management of NF should comprise of hemodynamic and respiratory evaluation and monitoring, broad-spectrum i.v. antimicrobial therapy, surgical debridement and nutritional support. Close postoperative management of NF patients remains of paramount importance.

Sinonasal sarcoidosis. A case report.

INTRODUCTION: Sarcoidosis is a granulomatous disease of unknown etiology, which in the majority of cases affects the lower respiratory tract. Although neck mass, parotid swelling and facial nerve palsy are considered the primary complaints in cases of head and neck sarcoidosis, sinonasal localization of the disease is also uncommonly reported. CASE: A 46 year old woman presented in our clinic with complaints of nasal congestion over a six month period. The patient reported increasing symptom severity in the last month with occasional purulent discharge. No other symptoms were reported. The patient's medical record was significant only for sarcoidosis localized to the lower respiratory tract. On anterior rhinoscopy, the nasal mucosa presented marked hypertrophy, purplish discoloration and granulomatous appearance of the inferior turbinates on the left side. The diagnosis of sinonasal sarcoidosis was made based on histopathologic examination of biopsy specimens. CONCLUSION: Sinonasal sarcoidosis presents a challenging issue for the clinicial as its mimicking features may be misleading and delay diagnosis. In the present paper we present a case of sinonasal sarcoidosis presenting as chronic rhinosinusitis.

Voice restoration after total laryngectomy using provox 2 (generation II) prosthesis.

BACKGROUND AND OBJECTIVES: Voice restoration after total laryngectomy is of outmost importance for patient and a therapeutic challenge for the surgeon and speech pathologist. Among various rehabilitation methods prosthetic voice yields nowadays the best results. PATIENTS AND METHODS: A total of 12 patients underwent laryngectomy at the Department of Otorhinolaryngology, University Hospital, Patras, Greece, between February 2006 and May 2007. All patients had advanced laryngeal squamous cell carcinoma. Eight patients had primary voice prosthesis inserted and four patients had a tracheo-esophageal puncture (TEP) carried out as a secondary procedure. RESULTS: The majority of the patients (80%) from both the primary insertion or the secondary insertion group, developed good and understood speech using the prosthesis. No significant difference in quality of speech was found between the two subgroups. Four patients required replacement of the prosthesis at intervals of 8 and 10 months after insertion, because of salivary leakage and granulation formation around the fistula, while 3 patients developed a mild mucositis and tracheitis due to postoperative radiotherapy. DISCUSSION: TEP puncture and prosthesis insertion is a relatively simple, safe and effective surgical procedure for voice restoration after laryngectomy. Provox 2 (generation II) voice prosthesis is a new and useful modified device that has overcome the previous prosthesis drawbacks, is well tolerated by the patients and can be easily changed via the front-loading technique.

Palatine tonsillar metastasis from lung adenocarcinoma.

Tonsillar metastasis from lung cancer is an extremely rare event and is usually related to metastatic spread of the neoplastic disease to other organs with poor prognosis. We present the unusual case of a 71-year-old man who developed a huge metastasis to the left palatine tonsil from a lung adenocarcinoma. The tumor was exophytic with necrotic and hemorrhagic areas, occupying a large portion of the oropharynx and producing airway obstruction, thus necessitating tracheostomy. Radiation therapy was delivered in an attempt to reduce the size of the tumor. Although a mild decrease of the tonsillar mass was noted, the designed therapy had to be discontinued because of a rapid deterioration of the patient's general condition. The patient finally died of disseminated disease. This case highlights the need for a thorough evaluation of a suspicious tonsillar enlargement, as this may be a sign of a primary malignancy elsewhere in the body.