Domenico Testa

CO2 laser surgery in the treatment of glottic cancer

The aim of the study was to assess the effectiveness of CO2 laser endoscopic surgery in the treatment of glottic carcinoma limited to the true vocal cords or involving the adjacent regions.

Store-Operated Ca2+ Entry Is Expressed in Human Endothelial Progenitor Cells

Endothelial progenitor cells (EPCs) may be recruited from the bone marrow to sites of tissue regeneration to sustain neovascularization and reendothelialization after acute vascular injury. This feature makes them particularly suitable for cell-based therapy. In mature endothelium, store-operated Ca(2+) entry (SOCE) is activated following emptying of inositol-1,4,5-trisphosphate-sensitive stores, and controls a wide number of functions, including proliferation, nitric oxide synthesis, and vascular permeability. The present work aimed at investigating SOCE expression in EPCs harvested from both peripheral blood (PB-EPCs) and umbilical cord blood (UCB-EPCs) by employing both Ca(2+) imaging and molecular biology techniques. SOCE was induced upon either pharmacological (ie, cyclopiazonic acid) or physiological (ie, ATP) depletion of the intracellular Ca(2+) pool. Further, store-dependent Ca(2+) entry was inhibited by the SOCE inhibitor, N-(4-[3,5-bis(trifluoromethyl)-1H-pyrazol-1-yl]phenyl)-4-methyl-1,2,3-thiadiazole-5-carboxamide (BTP-2). Real-time reverse transcription-polymerase chain reaction and western blot analyses showed that both PB-EPCs and UCB-EPCs express all the molecular candidates to mediate SOCE in differentiated cells, including TRPC1, TRPC4, Orai1, and Stim1. Moreover, pharmacological maneuvers demonstrated that, as well as in differentiated endothelial cells, the signal transduction pathway leading to depletion of the intracellular Ca(2+) pool impinged on the phospholipase C/inositol-1,4,5-trisphosphate pathway. Finally, blockage of SOCE with BTP-2 impaired PB-EPC proliferation. These findings provide the first evidence that EPCs express SOCE, which might thus be regarded as a novel target to enhance the regenerative outcome of cell-based therapy.

CO2 laser treatment of supraglottic cancer.

The aim of the study was to evaluate the effectiveness of endoscopic CO2 laser microsurgery in the management of supraglottic cancer.

Overexpression of the Cytokine Osteopontin Identifies Aggressive Laryngeal Squamous Cell Carcinomas and Enhances Carcinoma Cell Proliferation and Invasiveness

Purpose: Osteopontin is a secreted cytokine that binds to the cell surface CD44v6 receptor. We studied osteopontin and CD44v6 expression in laryngeal squamous cell carcinomas and correlated osteopontin expression levels with clinicopathologic tumor features. Experimental Design: We used immunohistochemistry, immunoblotting, and reverse transcription-PCR to study osteopontin expression in 58 laryngeal squamous cell carcinomas. Cultured squamous carcinoma cells were treated with exogenous osteopontin or with RNA interference to knockdown osteopontin expression. Results: Osteopontin expression was higher in all the invasive carcinomas than in patient-matched normal mucosa. Its expression levels were significantly correlated with tumor stage and grade and with the presence of lymph node and distant metastases. Osteopontin positivity was negatively correlated with overall survival (P = 0.03). Osteopontin expression was paralleled by intense cell surface reactivity for CD44v6. Treatment of squamous carcinoma cells with recombinant osteopontin sharply increased proliferation and Matrigel invasion in comparison with the untreated cells parallel to activation of the mitogen-activated protein kinase/extracellular signal-regulated kinase kinase/mitogen-activated protein kinase signaling cascade. Osteopontin knockdown by RNA interference, anti-CD44 antibodies, and mitogen-activated protein kinase/extracellular signal-regulated kinase kinase inhibition prevented these effects. Conclusions: These results identify osteopontin as a marker and a potential therapeutic target in cases of aggressive laryngeal squamous cell carcinomas.

Morphological, diagnostic and surgical features of ectopic thyroid gland: A review of literature

Ectopic thyroid tissue remains a rare developmental abnormality involving defective or aberrant embryogenesis of the thyroid gland during its passage from the floor of the primitive foregut to its usual final position in pre-tracheal region of the neck. Its specific prevalence accounts about 1 case per 100.000-300.000 persons and one in 4.000-8.000 patients with thyroid disease show this condition. The cause of this defect is not fully known. Despite genetic factors have been associated with thyroid gland morphogenesis and differentiation, just recently some mutation has been associated with human thyroid ectopy. Lingual region in the most common site of thyroid ectopy but ectopic thyroid tissue were found in other head and neck locations. Nevertheless, aberrant ectopic thyroid tissue has been found in other places distant from the neck region. Ectopic tissue is affected by different pathological changes that occur in the normal eutopic thyroid. Patients may present insidiously or as an emergency. Diagnostic management of thyroid ectopy is performed by radionuclide thyroid imaging, ultrasonography, CT scan, MRI, biopsy and thyroid function tests. Asymptomatic euthyroid patients with ectopic thyroid do not usually require therapy but are kept under observation. For those with symptoms, treatment depends on size of the gland, nature of symptoms, thyroid function status and histological findings. Surgical excision is often required as treatment for this condition.

Oxidative stress in chronic otitis media with effusion

Abstract Conclusions: The high oxidant levels in chronic otitis media with effusion (OME) observed in our research and the improvement seen in children with chronic OME after antioxidant treatment suggest that oxygen-derived free radicals play an important role in chronic OME. Objectives: OME is a common pathologic condition characterized by nonpurulent fluid in the middle ear (ME) that leads to moderate conductive hearing loss and flat tympanogram. During OME inflammatory cells generate large amounts of superoxide radicals to improve bactericidal activity. Overproduction of oxygen-derived free radicals induces oxidative damage in humans. Glutathione (GSH) is one of the major components of the antioxidant system that protects cells from oxidative stress. The aim of the study was to evaluate oxidative stress in chronic OME by investigation of ME fluids collected during myringotomy. Methods: During myringotomy, fluid was collected from the ME to evaluate lipid peroxide levels in the effusion. Fifty-nine children with ME effusion without any resolution after repeated medical treatments were enrolled in the study. Results: Lipid peroxide levels in all samples were high (mean 11.5 nmole/million cells), similar to the values found in other chronic diseases. GSH might be employed during surgery while applying ventilation tubes and after surgery to prevent oxidative stress.

OPN/CD44v6 overexpression in laryngeal dysplasia and correlation with clinical outcome

Laryngeal dysplasia is a common clinical concern. Despite major advancements, a significant number of patients with this condition progress to invasive squamous cell carcinoma. Osteopontin (OPN) is a secreted glycoprotein, whose expression is markedly elevated in several types of cancers. We explored OPN as a candidate biomarker for laryngeal dysplasia. To this aim, we examined OPN expression in 82 cases of dysplasia and in hyperplastic and normal tissue samples. OPN expression was elevated in all severe dysplasia samples, but not hyperplastic samples, with respect to matched normal mucosa. OPN expression levels correlated positively with degree of dysplasia (P=0.0094) and negatively with disease-free survival (P<0.0001). OPN expression was paralleled by cell surface reactivity for CD44v6, an OPN functional receptor. CD44v6 expression correlated negatively with disease-free survival, as well (P=0.0007). Taken as a whole, our finding identify OPN and CD44v6 as predictive markers of recurrence or aggressiveness in laryngeal intraepithelial neoplasia, and overall, point out an important signalling complex in the evolution of laryngeal dysplasia.

Glutathione in the Upper Respiratory Tract

Glutathione (GSH), a major extracellular antioxidant, has been found in high concentrations in the epithelial lining fluid of the lower respiratory tract The GSH concentrations in nasal fluid, in normal and pathologic conditions, were investigated and found to be very low. A GSH aerosol (600 mg daily for 10 days) increased GSH levels in the nasal mucosa and induced a statistically significant improvement in nasal obstruction, rhinorrhea, and ear fullness. Thus, GSH administered by aerosol could be a means of defending the epithelial respiratory cells against a toxic oxidant.

Management of chronic otitis media with effusion: the role of glutathione.

Background The inflammatory cells documented in chronic otitis media with effusion (OME) spontaneously release oxidants which can induce middle ear (ME) epithelial cell damage. Glutathione (GSH), a major extracellular antioxidant in humans, plays a central role in antioxidant defense.

Inferior turbinate osteoma: a rare cause of nasal obstruction.

Osteoma of the nose is a rare and benign tumor that develops slowly with an incidence of 0.6% of all benign tumors of the nose. It is the most common benign tumor of the paranasal sinuses and is usually asymptomatic and found only on a coincidental radiographic investigation. Osteoma frequently occurs in the frontal sinus (52%) followed by ethmoid (22.0%), and maxillary sinus (5.1%), most rarely in the sphenoid (1.7%), and in the nose (0.6%). Osteomas may occur at any age but usually present in the second-to-fourth decades with a slight male:female preponderance. We present an unusual and rare case of patient with an osteoma of the inferior turbinate.