P-glycoprotein inhibition with verapamil overcomes mometasone resistance in Chronic Sinusitis with Nasal Polyps.

BACKGROUND: P-glycoprotein (P-gp) is a membrane efflux pump which is overexpressed in Chronic Rhinosinusitis with Nasal Polyps (CRSwNP) and promotes Type 2 inflammation. Glucocorticoids (GC) are substrates of P-gp suggesting that overexpression may additionally contribute to GC resistance in CRSwNP. This study aims to determine whether P-gp inhibition using verapamil enhances mometasone retention and efficacy in nasal polyp explants. METHODOLOGY: IRB approved study in which organotypic polyp explants were exposed to mometasone (4.15 µg/mL) and verapa- mil (125 µg/mL) as mono and combination therapy. The effect of verapamil on mometasone tissue retention over time was deter- mined using HPLC. The effect of verapamil on mometasone anti-inflammatory function was determined using ELISA for secreted IL-5. Groups were compared using Kruskal-Wallis test. RESULTS: P-gp expression strongly and significantly inversely correlated with mometasone retention 1hr after exposure, with a ne- arly 6-fold reduction in tissue retention between the lowest and highest P-gp expressing polyp explants. P-gp inhibition reversed this effect and significantly improved mometasone retention at 1hr relative to mometasone alone. The combination of mome- tasone and verapamil significantly reduced IL-5 secretion relative to vehicle control and outperformed either treatment alone. CONCLUSIONS: Our study confirms that P-gp contributes to mometasone resistance. This P-gp mediated resistance was successfully reversed by addition of the P-gp inhibitor verapamil. Verapamil further significantly enhanced the anti-inflammatory effect of mometasone when given as a combination therapy.

Pre-treatment apparent diffusion coefficient mapping: differentiation of benign from malignant laryngeal lesions.

OBJECTIVE: To determine whether a threshold apparent diffusion coefficient value may help to differentiate laryngeal carcinomas from benign lesions. METHODS: Fifty-three patients with laryngeal masses were recruited; four of them were excluded because of susceptibility artefacts. In the remaining 49 patients, the pathological results showed 32 laryngeal carcinomas and 17 benign lesions. The diagnostic value of diffusion-weighted magnetic resonance imaging for the identification of malignant lesions was determined. In addition, the agreement between diffusion-weighted magnetic resonance imaging and histopathology was assessed. Moreover, the sensitivity, specificity, and negative and positive predictive values of the apparent diffusion coefficient in detecting benign and malignant lesions were analysed. An apparent diffusion coefficient histogram was also produced. RESULTS: An apparent diffusion coefficient value of 1.1 × 10-3 mm2/second produced the best result when used as the cut-off point to differentiate malignant from benign masses. CONCLUSION: An apparent diffusion coefficient threshold of 1.1 × 10-3 mm2/second is optimal for distinguishing laryngeal carcinomas from benign lesions. Apparent diffusion coefficient values were lower for patients with laryngeal carcinomas than for those with benign lesions.