Pathogenesis of chronic rhinosinusitis with nasal polyps: role of IL-6 in airway epithelial cell dysfunction.

BACKGROUND: Chronic rhinosinusitis with nasal polyps (CRSwNP) is characterized by an alteration in airway epithelial cell functions including barrier function, wound repair mechanisms, mucociliary clearance. The mechanisms leading to epithelial cell dysfunction in nasal polyps (NPs) remain poorly understood. Our hypothesis was that among the inflammatory cytokines involved in NPs, IL-6 could alter epithelial repair mechanisms and mucociliary clearance. The aim of this study was to evaluate the in vitro effects of IL-6 on epithelial repair mechanisms in a wound repair model and on ciliary beating in primary cultures of Human Nasal Epithelial Cells (HNEC). METHODS: Primary cultures of HNEC taken from 38 patients during surgical procedures for CRSwNP were used in an in vitro model of wound healing. Effects of increasing concentrations of IL-6 (1 ng/mL, 10 ng/mL, and 100 ng/mL) and other ILs (IL-5, IL-9, IL-10) on wound closure kinetics were compared to cultures without IL-modulation. After wound closure, the differentiation process was characterized under basal conditions and after IL supplementation using cytokeratin-14, MUC5AC, and ßIV tubulin as immunomarkers of basal, mucus, and ciliated cells, respectively. The ciliated edges of primary cultures were analyzed on IL-6 modulation by digital high-speed video-microscopy to measure: ciliary beating frequency (CBF), ciliary length, relative ciliary density, metachronal wavelength and the ciliary beating efficiency index. RESULTS: Our results showed that: (i) IL-6 accelerated airway wound repair in vitro, with a dose-response effect whereas no effect was observed after other ILs-stimulation. After 24 h, 79% of wounded wells with IL6-100 were fully repaired, vs 46% in the IL6-10 group, 28% in the IL6-1 group and 15% in the control group; (ii) specific migration analyses of closed wound at late repair stage (Day 12) showed IL-6 had the highest migration compared with other ILs (iii) The study of the IL-6 effect on ciliary function showed that CBF and metachronal wave increased but without significant modifications of ciliary density, length of cilia and efficiency index. CONCLUSION: The up-regulated epithelial cell proliferation observed in polyps could be induced by IL-6 in the case of prior epithelial damage. IL-6 could be a major cytokine in NP physiopathology.

Prognostic value and therapeutic implications of nodal involvement in head and neck mucosal melanoma.

BACKGROUND: The prognostic significance of nodal involvement is not well established in head and neck mucosal melanoma (HNMM). METHODS: A retrospective, monocentric study was performed on 96 patients with HNMM treated between 2000 and 2017. RESULTS: At diagnosis, seventeen patients (17.8%) were cN1, with a higher risk for HNMM arising from the oral cavity (p = 0.01). cN status had no prognostic value in patients with nonmetastatic resectable HNMM. No occult nodal metastasis was observed in the cN0 patients after a nodal dissection (ND). The nodal recurrence rate was similar in the cN1 and the cN0 patients. No isolated nodal recurrences were noted. Among the patients who underwent a ND, no benefit of this procedure was noted. CONCLUSIONS: cN1 status is not a prognostic factor in patients with resectable HNMM. Elective ND should not be systematically performed in cN0 HNMM.

Risk-based stratification in head and neck mucosal melanoma.

BACKGROUND: Head and neck mucosal melanoma (HNMM) is a rare and aggressive disease with a high metastatic potential. Two staging systems are currently available: one specific to HNMM (mmTNM) and one specific to primary tumour sites (sccTNM). Our main objective was to assess the prognostic value of both of these classifications in order to allow accurate risk-based classification. METHODS: We performed a retrospective cohort study of patients with HNMM treated consecutively between 2000 and 2017. All of the patients were restaged using the mmTNM and the sccTNM. A prognostic analysis was carried out according to both staging systems. RESULTS: There were 96 patients with an HNMM in our cohort, of whom 80 underwent surgical treatment followed by radiotherapy. The median overall survival (OS) and progression-free survival (PFS) for the operated patients were 39 months (95% CI, 21.6-56.4 months) and 18 months (95% CI, 6.5-29.5 months), respectively. A paranasal sinus localization was associated with lower survival compared to a nasal cavity primary localization (p < 1 0-4). Both of the classifications correlated with OS, PFS, and distant metastasis-free survival. High-risk HNMM were characterized as T4/stage IV by the mmTNM and T3-4/stage III-IV by the sccTNM. Given the primary tumour location, both TNM classifications were suitable for risk-stratification of sinonasal mucosal melanomas. However, combining both TNM, we defined new stages mmT3A and mmT3B according to sccTNM with a more accurate risk stratification (p < 1 0-4). CONCLUSIONS: Both of the classifications should be combined, in order to improve the risk-stratification of patients with HNMM.

Investigating hyperventilation syndrome in patients suffering from empty nose syndrome.

OBJECTIVES/HYPOTHESIS: Patients with empty nose syndrome (ENS) following turbinate surgery often complain about breathing difficulties. We set out to determine if dyspnea in patients with ENS was associated with hyperventilation syndrome (HVS). We hypothesized that lower airway symptoms in ENS could be explained by HVS. STUDY DESIGN: Observational prospective study. METHODS: All consecutive patients referred to our center for ENS over 1 year were invited to participate. Patients completed the Nijmegen score and underwent a hyperventilation provocation test (HVPT) and arterial blood gas and cardiopulmonary tests. HVS was defined by a delayed return of the end-tidal partial pressure of carbon dioxide in the expired gas to baseline during HVPT. Patients with HVS were asked to complete the Sinonasal Outcome Test (SNOT)-16 questionnaire before and after a specific eight-session respiratory rehabilitation program. RESULTS: Twenty-two of the 29 patients referred for ENS during the study period were eligible for inclusion and underwent a complete workup. HVS was diagnosed in 17 of these patients (77.3%). In the five patients who completed the SNOT-16, the score was significantly lower after rehabilitation. CONCLUSIONS: This study suggests that HVS is frequent in patients with ENS, and that symptoms can be improved by respiratory rehabilitation. Pathophysiological links between ENS and HVS deserve to be further explored. LEVEL OF EVIDENCE: 2b Laryngoscope, 127:1983-1988, 2017.