Effects of Wnt signaling on epithelial to mesenchymal transition in chronic rhinosinusitis with nasal polyp.

BACKGROUND: Epithelial to mesenchymal transition (EMT) is associated with the pathophysiology of chronic rhinosinusitis with nasal polyp (CRSwNP). Wnt signaling is causative for EMT, whereas the mechanism in CRSwNP is not fully understood. OBJECTIVE: We sought to evaluate the role of Wnt signaling in EMT of CRSwNP using a murine nasal polyp (NP) model and human tissues. METHODS: Inflammatory markers and EMT-related molecules were evaluated in NP models using adenomatosis polyposis coli (Apc)Min/+ mice with activated Wnt signaling and NP models treated with Wnt signaling inhibitor, indocyanine green-001 (ICG-001). EMT markers and Wnt signaling-associated mediators were analysed using human sinonasal tissues from control subjects and CRSwNP patients. RESULTS: ApcMin/+ mice-induced NPs exhibited more frequent polypoid lesions and upregulation of Wnt-related molecules, including nuclear ß-catenin, WNT3A and cyclin D1. Markers of EMT were significantly overexpressed in the ApcMin/+ NP mice (p<0.001 for E-cadherin and α-smooth muscle actin), and interleukin (IL)-17A+ cells and neutrophilic infiltration were increased in ApcMin/+ NP mice (p<0.001). Inhibition of Wnt signaling via ICG-001 resulted in significantly decreased nasal polypoid lesions (p<0.001), EMT-related markers (p=0.019 for E-cadherin and p=0.002 for vimentin) and the mRNA levels of IL-4 (p<0.001) and IL-17A (p=0.004) compared with the positive control group. Finally, nuclear ß-catenin (p=0.042) was significantly increased compared with the control, and the expression levels of Wnt ligands and receptors were upregulated in human NP tissues (p=0.045 for WNT3A and p=0.042 for FZD2), suggesting increased Wnt signaling and EMT in CRSwNP. CONCLUSION: Wnt signaling may contribute to the pathogenesis of NPs through EMT. Therefore, inhibition of Wnt signaling may be a potential therapeutic strategy for patients with CRSwNP.

IL-25 Could Be Involved in the Development of Allergic Rhinitis Sensitized to House Dust Mite.

BACKGROUND AND PURPOSE: When house dust mite (HDM), a common allergen, comes into the mucosal membrane, it may stimulate innate immunity. However, the precise role of interleukin- (IL-) 25 in the development of HDM-induced nasal allergic inflammation is still unclear. Therefore, we investigated the role of IL-25 in allergic rhinitis (AR) patients sensitized to HDM. METHODS: To confirm the production of IL-25 in human nasal epithelial cells (HNECs), we stimulated HNECs. IL-25 expression in the nasal mucosa from control, non-AR (NAR) patients, and HDM-sensitized AR patients was assessed using immunohistochemistry, and quantitative reverse transcription PCR. Correlations between IL-25 and other inflammatory markers were explored. RESULTS: An in vitro study showed significantly elevated concentrations of IL-25 in the HNEC samples with highest doses of HDM. Nasal tissues from AR patients sensitized to HDM showed significantly higher IL-25 expression, compared to those from the control or NAR patients. Moreover, the expression of IL-25 in nasal tissues from AR patients sensitized to HDM was positively associated with Th2 markers, such as ECP and GATA3. CONCLUSIONS: IL-25 expression increased with high-dose HDM stimulation and was related to Th2 markers. Therefore, IL-25 neutralization might offer a new strategy for treating patients with HDM-sensitized AR.

Regenerative and proliferative activities of chondrocyte based on the degree of perichondrial injury in rabbit auricular cartilage.

Although the regeneration process for injured cartilage requires an intact perichondrium, few studies have addressed the importance of the intact perichondrial layer in the regeneration of damaged cartilage. In this study, we evaluated the role of the perichondrium on regenerative activities in injured cartilage according to different degrees of perichondrial injury. Auricular cartilage harvested from six New Zealand white rabbits was irradiated with a 1,460-nm diode laser at two different power settings (0.3 or 0.5 W). Irradiated cartilage was reimplanted into a subperichondrial pocket under three different conditions: non-injured perichondrium (NPI), unilaterally injured perichondrium (UPI), or bilaterally injured perichondrium (BPI). Rabbits were sacrificed at 1, 2, and 4 weeks after reimplantation and the auricular cartilage was reharvested. A histopathological study using hematoxylin and eosin staining, a live/dead viability assay, and immunohistochemical staining for proliferating cell nuclear antigen were performed to evaluate structural changes and regenerative and proliferative activities of the injured chondrocytes. A modified array and restored boundary of chondrocytes were observed in the NPI and UPI groups. Regeneration of chondrocytes was prominent in the NPI and UPI groups, but was not observed in the BPI group. Proliferative activity of chondrocytes was observed only when the perichondrium was preserved in the NPI and UPI groups. In contrast, proliferative activity was not observed until 4 weeks in the BPI group. The degree of perichondrial injury affected proliferation and regeneration in injured elastic cartilage. In the case of unilateral perichondrial injury, the surgeon should be careful to avoid damaging the other side of the perichondrium, because at least a unilateral perichondrial layer is needed for the regeneration of elastic cartilage.

Increased Anti-Allergic Effects of Secretome of Low-Level Light Treated Tonsil-Derived Mesenchymal Stem Cells in Allergic Rhinitis Mouse Model.

BACKGROUND: Low-level light therapy (LLLT) is widely used for the photobiomodulation of cell behavior. Recent studies have shown that LLLT affects the proliferation and migration of various types of mesenchymal stem cells (MSCs). However, there is a lack of studies investigating the effect of LLT on enhancing the immunomodulatory properties of tonsil-derived MSCs (T-MSCs). OBJECTIVE: The aim of this study was to investigate the immunomodulatory effects of conditioned media from T-MSCs (T-MSCs-CM) treated with LLLT in allergic inflammation. METHODS: We isolated T-MSCs from human palatine tonsils and evaluated the ingredients of T-MSCs-CM. The effect of T-MSCs-CM treated with LLLT was evaluated in a mouse model of allergic rhinitis (AR). We randomly divided the mice into four groups (negative control, positive control, T-MSCs-CM alone, and T-MSCs-CM treated with LLLT). To elucidate the therapeutic effect, we assessed rhinitis symptoms, serum immunoglobulin (Ig), the number of inflammatory cells, and cytokine expression. RESULTS: We identified increased expression of immunomodulatory factors, such as HGF, TGF-ß, and PGE, in T-MSCs-CM treated with LLLT, compared to T-MSCs-CM without LLLT. Our animal study demonstrated reduced allergic symptoms and lower expression of total IgE and OVA-specific IgE in the LLLT-treated T-MSCs-CM group compared to the AR group and T-MSCs-CM alone. Moreover, we found that T-MSCs-CM treated with LLLT showed significantly decreased infiltration of eosinophils, neutrophils, and IL-17 cells in the nasal mucosa and reduced IL-4, IL-17, and IFN-γ expression in OVA-incubated splenocytes compared to the AR group. CONCLUSIONS: The present study suggests that T-MSCs-CM treated with LLLT may provide an improved therapeutic effect against nasal allergic inflammation than T-MSCs-CM alone.

Clinical Efficacy and Safety of Low-Level Laser Therapy in Patients with Perennial Allergic Rhinitis: A Randomized, Double-Blind, Placebo-Controlled Trial.

Allergic rhinitis (AR) is a common disease that interferes with the daily activities and reduces the quality of life. Conventional treatments often do not provide complete resolution of the symptoms, and many new treatment modalities have been tried. This study aimed to evaluate the efficacy and safety of low-level laser therapy (LLLT) for AR in a randomized, double-blind, placebo-controlled trial. Patients diagnosed with AR were randomly allocated to receive LLLT or sham treatment. The primary outcome was a change in the reflective total nasal symptom score (TNSS). The secondary outcome was quality of life scores assessed using the Rhinoconjunctivitis Quality of Life Questionnaire. Incidences of adverse events were also recorded. Among 67 randomized subjects, 41 subjects (22 in LLLT group and 19 in sham treatment group) were included for efficacy analysis. The LLLT group showed a significantly improved TNSS score compared to the sham treatment group for decreasing AR symptom severity (p = 0.011) and improving quality of life regarding nasal symptoms (p = 0.036) at the end of treatment. Throughout the treatment period, no severe adverse events occurred. This clinical trial showed that LLLT is an effective and safe option for the management of AR regarding symptom relief and quality of life improvement.

Role of IL-17A in Chronic Rhinosinusitis With Nasal Polyp.

PURPOSE: Th17-associated inflammation is increased in chronic rhinosinusitis with nasal polyp (CRSwNP), and is associated with disease severity and steroid resistance. Overexpressed interleukin (IL)-17A affects CRSwNP by tissue remodeling, eosinophilic accumulation, and neutrophilic infiltration. We aimed to identify the role of IL-17A in CRSwNP and to evaluate the effects of anti-IL-17A blocking antibody on nasal polyp (NP) formation using a murine NP model. Moreover, we sought to investigate whether the inhibition of mechanistic target of the rapamycin (mTOR) signal pathway could suppress IL-17A expression and NP formation. METHODS: Human sinonasal tissues from control subjects and patients with chronic rhinosinusitis (CRS) were analyzed using immunohistochemistry (IHC) and immunofluorescence staining. The effects of IL-17A neutralizing antibody and rapamycin were evaluated in a murine NP model. Mouse samples were analyzed using IHC, quantitative real-time polymerase chain reaction, and enzyme-linked immunosorbent assay. RESULTS: IL-17A⁺ inflammatory cells were significantly increased in number in NP from patients with CRSwNP compared to that in uncinate process tissues from control subjects and patients with CRS without NP or CRSwNP. CD68⁺ M1 macrophages dominantly expressed IL-17A, followed by neutrophils and T helper cells, in NP tissues. Neutralization of IL-17A effectively reduced the number of NPs, inflammatory cytokines, and IL-17A-producing cells, including M1 macrophages. Inhibition of IL-17A via the mTOR pathway using rapamycin also attenuated NP formation and inflammation in the murine NP model. CONCLUSIONS: IL-17A possibly plays a role in the pathogenesis of CRSwNP, the major cellular source being M1 macrophage in NP tissues. Targeting IL-17A directly or indirectly may be an effective therapeutic strategy for CRSwNP.

Strain-Specific Differences in House Dust Mite (Dermatophagoides farinae)-Induced Mouse Models of Allergic Rhinitis.

OBJECTIVES: Limited information is available regarding strain-related differences in mouse models of allergic rhinitis induced by Dermatophagoides farinae (Der f1). In this study, we compared differences between two mouse strains and determined the optimal dose of Der f1 for allergic rhinitis mouse models. METHODS: Forty-eight mice were assigned to the following six groups (n=8 per group): group A (control, BALB/c), group B (Der f1-sensitized BALB/c, 25 µg), group C (Der f1-sensitized BALB/c, 100 µg), group D (control, C57BL/6), group E (Der f1-sensitized C57BL/6, 25 µg), and group F (Der f1-sensitized C57BL/6, 100 µg). Allergic inflammation was induced with Der f1 and alum sensitization, followed by an intranasal challenge with Der f1. Rubbing and sneezing scores, eosinophil and neutrophil infiltration, and immunoglobulin, cytokine, and chemokine levels in the nasal mucosa and from splenocyte cultures were assessed. RESULTS: Rubbing and sneezing scores were higher in groups B, C, E, and F than in groups A and D, with a similar pattern in both strains (i.e., group B vs. E and group C vs. F). Serum immunoglobulin levels were significantly elevated compared to the control in groups B and C, but not in groups E and F. Eosinophil and neutrophil infiltration increased (all P<0.05) after the Der f1 challenge (groups B, C, E, and F) compared to the control (groups A and D) in both the BALB/c and C57BL/6 strains, without any significant difference between the two strains (group A vs. D, group B vs. E, and group C vs. F) (P>0.05). BALB/c mice (group B) showed a greater elevation of splenic interleukin (IL)-4 (P<0.01), IL-5 (P<0.01), and IL-6 levels (P<0.05) and nasal IL-4 mRNA levels (P<0.001) than the C57BL/6 mice (group E). Interestingly, mice treated with 100 µg Der f1 showed a weaker allergic response than those treated with 25 µg. CONCLUSION: We found 25 µg to be a more appropriate dose for Der f1 sensitization. BALB/c mice are more biased toward a Th2 response and are a more suitable model for allergic rhinitis than C57BL/6 mice. This study provides information on the appropriate choice of a mouse model for allergic rhinitis.

Inhibition of IRF4 in dendritic cells by PRR-independent and -dependent signals inhibit Th2 and promote Th17 responses.

Cyclic AMP (cAMP) is involved in many biological processes but little is known regarding its role in shaping immunity. Here we show that cAMP-PKA-CREB signaling (a pattern recognition receptor [PRR]-independent mechanism) regulates conventional type-2 Dendritic Cells (cDC2s) in mice and reprograms their Th17-inducing properties via repression of IRF4 and KLF4, transcription factors essential for cDC2-mediated Th2 induction. In mice, genetic loss of IRF4 phenocopies the effects of cAMP on Th17 induction and restoration of IRF4 prevents the cAMP effect. Moreover, curdlan, a PRR-dependent microbial product, activates CREB and represses IRF4 and KLF4, resulting in a pro-Th17 phenotype of cDC2s. These in vitro and in vivo results define a novel signaling pathway by which cDC2s display plasticity and provide a new molecular basis for the classification of novel cDC2 and cDC17 subsets. The findings also reveal that repressing IRF4 and KLF4 pathway can be harnessed for immuno-regulation.

The Impact of Allergic Rhinitis on Symptom Improvement in Pediatric Patients After Adenotonsillectomy.

OBJECTIVES: It is well known that allergic rhinitis (AR) has positive association with adenotonsillectomy. However, the impact of AR on symptom improvement after adenotonsillectomy is not well documented. Hence, we aimed to evaluate the effect of AR on the symptom improvement after adenotonsillectomy between AR and nonallergic patients. METHODS: A retrospective analysis was performed on 250 pediatric patients younger than 10 years old who received adenotonsillectomy from June 2009 to June 2014 in a tertiary referral hospital. All patients underwent skin prick test or multiple allergen simultaneous test (MAST) before surgery and classified into AR group and control group. Obstructive and rhinitis symptoms including snoring, mouth breathing, nasal obstruction, rhinorrhea, itching, and sneezing were evaluated before and 1 year after surgery using questionnaire and telephone survey. RESULTS: AR group was 131 and control group was 119, showing higher prevalence (52.4%) of AR among adenotonsillectomized patients. Both groups showed dramatic improvement of symptoms such as snoring and mouth breathing after surgery (all P<0.05). However, AR group showed significantly less improvement than control group in snoring, mouth breathing, nasal obstruction, and rhinorrhea (all P<0.05). Multivariate analysis showed that preoperative mouth breathing and snoring were dependent on tonsil grade and postoperative symptoms were mainly dependent on presence of AR. Nasal obstruction was dependent on tonsil grade and presence of AR preoperatively and presence of AR postoperatively. These suggest the importance of AR as a risk factor for mouth breathing, snoring, and nasal obstruction. CONCLUSION: AR has positive association with adenotonsillectomy and not only allergic symptoms but also obstructive symptoms such as snoring and mouth breathing improved less in AR group than control group. Hence, patients with AR should be monitored for long-term basis and more carefully after adenotonsillectomy.

Effect of Topical Propolis on Wound Healing Process After Tonsillectomy: Randomized Controlled Study.

OBJECTIVES: The post-tonsillectomy pain and post-tonsillectomy hemorrhage are the two main problems after tonsillectomy. The aim of this study was to investigate the beneficial effects of water soluble ethanol extract propolis on post-tonsillectomy patient. METHODS: One hundred and thirty patients who underwent tonsillectomy or adenotonsillectomy were randomly divided into the control and propolis groups, each including 65 patients. The propolis group was applied with propolis orally immediately after surgery and by gargle. The pain scores were assessed on post-tonsillectomy 0, 1st, 2nd, 3rd, and 7th-10th day using a visual analogue scale score. Postoperative wound healing was evaluated by scoring pinkish membrane of tonsillar fossae on postoperative days 3 and 7-10. The incidence of post-tonsillectomy bleeding was examined in each group. RESULTS: Post-tonsillectomy pain was significantly less in propolis group compared to control group on postoperative days 3 and 7-10. Post-tonsillectomy hemorrhage was significantly less in the propolis group compared to the control group (P<0.05). The wound healing was significantly better in the propolis group compared to the control group on postoperative day 7-10 (P=0.002). CONCLUSION: Applying the propolis to post-tonsillectomy wound showed beneficial effect of reducing postoperative pain, preventing hemorrhage, and accelerating of wound healing of tonsillar fossae.

Intranasal Helicobacter pylori colonization does not correlate with the severity of chronic rhinosinusitis.

OBJECTIVE: To investigate the prevalence of Helicobacter pylori (HP) in the nasal cavity of patients with chronic rhinosinusitis (CRS) and to correlate it with the severity of CRS. STUDY DESIGN AND SETTING: Intranasal HP was investigated using rapid urease (CLO) testing and immunohistochemical (IHC) analysis and confirmed with transmission electron microscopy. To evaluate the severity of sinusitis, CT scans were graded according to the Lund-MacKay scoring system, and CRS symptom scores were recorded. RESULTS: Twelve of 48 patients (25.0%) were positive, but only 1 of 29 (3.4%) controls was positive for both CLO testing and IHC analysis (P = 0.025). The mean preoperative CT grade (P = 0.439) and symptom scores (P = 0.515) were not related to the severity of CRS. CONCLUSIONS: Intranasal HP was more prevalent in patients with CRS than healthy controls. However, there was no significant correlation observed between the severity of sinusitis and intranasal HP colonization. SIGNIFICANCE: HP has a limited role in pathogenesis of CRS.

Hyperostosis may affect prognosis after primary endoscopic sinus surgery for chronic rhinosinusitis.

OBJECTIVE: To investigate the independent effect of hyperostosis on outcome after endoscopic sinus surgery (ESS) in patients with chronic rhinosinusitis (CRS). STUDY DESIGN AND SETTING: The medical records of 81 consecutive patients who had undergone primary ESS for CRS were reviewed retrospectively. Sinus CT scans were evaluated for the presence of hyperostosis to investigate the association with postoperative outcomes. The independent effect of hyperostosis on surgical outcome was analyzed, controlling for possible confounding factors with a multiple logistic regression model. RESULTS: Sixty percent of the patients showed hyperostosis, and there was a statistically significant association between the hyperostosis and postoperative outcome (P = 0.035, chi(2) test), which was confirmed after adjustment for the possible confounding factors (P = 0.048, odds ratio [OR] = 3.19, logistic regression analysis). CONCLUSIONS: Our study suggests that patients with CRS who have hyperostosis may have a poorer surgical outcome than those without hyperostosis. EBM RATING: B-2b.

Clinical characteristics of chronic rhinosinusitis with asthma.

OBJECTIVE: This study was directed at identifying clinical features of chronic rhinosinusitis with asthma, and examining the differences of the postoperative outcomes in asthmatics and nonasthmatics. STUDY DESIGN AND SETTING: Twenty-one asthmatic and 77 nonasthmatic patients who underwent functional endoscopic sinus surgery (FESS) were entered into the study. The following six parameters were determined in asthmatic and nonasthmatic groups; the presence of allergy, previous sinus surgery, severity of preoperative rhinosinusitis symptoms, improvements in postoperative rhinosinusitis symptoms, preoperative disease extent, and postoperative endoscopic outcomes. RESULTS: Symptom scores improved significantly in both asthmatics and nonasthmatics postoperatively, and asthmatics exhibited significantly worse postoperative endoscopic outcomes compared with nonasthmatics. No difference was found in other parameters between two groups. Multivariate analysis revealed asthma continues to be an independent predictor of success. CONCLUSIONS: The present study found that chronic rhinosinusitis in asthmatics showed worse postoperative outcomes than in nonasthmatics, and every attempt should be made for the improvement of surgical results in these patients.

Effect of a Chitosan Gel on Hemostasis and Prevention of Adhesion After Endoscopic Sinus Surgery.

OBJECTIVES: Postoperative bleeding and adhesion formation are the two most common complications after endoscopic sinus surgery (ESS). The former sometimes can be life threatening and the latter is the most common reason requiring revision surgery. This study was designed to evaluate the effect of newly developed chitosan gel (8% carboxymethyl chitosan, Surgi shield) on hemostasis and wound healing after ESS. METHODS: A prospective, randomized, double-blind controlled trial was conducted in 33 patients undergoing symmetric ESS. At the conclusion of the operation, Surgi shield was randomly applied on one side of the nasal cavity, with the opposite side acting as control and the bleeding quantity of the surgical field was evaluated every 2 minutes. And then, Merocel was placed in the ethmoidectomized areas of the both sides. Five milliliters of Surgi shield was applied to the Merocel of intervention side and saline was applied to the other side. Merocel in both nasal cavities was removed and 5 mL of Surgi shield was applied again to the intervention side on the second day after surgery. The nasal cavity was examined using a nasal endoscope and the degree of adhesion, crusting, mucosal edema, infection, and granulations were graded at 1, 2, and 4 weeks after surgery. RESULTS: Complete hemostasis was rapidly achieved in the Surgi shield applied side compared with the control side at 2, 4, 6, 8, and 10 minutes after application of Surgi shield (P=0.007, P=0.004, P<0.001, P=0.001, and P<0.001, respectively). There were significantly less adhesions on the Surgi shield applied side at postoperative 1, 2, and 4 weeks (P=0.001, P<0.001, and P<0.001, respectively). The degree of mucosal edema, infection, crusting, or granulation formation assessed by the endoscopic features in the Surgi shield applied side was not significantly different from that of the control side (P>0.05). No adverse effects were noted in the patient series. CONCLUSION: Surgi shield containing chitosan can be used safely to achieve rapid hemostasis immediately after ESS and to prevent adhesion formation.

The role of TRPV1 in the CD4+ T cell-mediated inflammatory response of allergic rhinitis.

Transient receptor potential vanilloid 1 (TRPV1), which has been identified as a molecular target for the activation of sensory neurons by various painful stimuli, was reported to regulate the signaling and activation of CD4+ T cells. However, the role of TRPV1 in CD4+ T cell in allergic rhinitis remains poorly understood. In this study, TRPV1 expression was localized in CD4+ T cells. Both knockout and chemical inhibition of TRPV1 suppressed Th2/Th17 cytokine production in CD4 T cells and Jurkat T cells, respectively, and can suppress T cell receptor signaling pathways including NF-κB, MAP kinase, and NFAT. In TRPV1 knockout allergic rhinitis (AR) mice, eosinophil infiltration, Th2/Th17 cytokines in the nasal mucosa, and total and ova-specific IgE levels in serum decreased, compared with wild-type AR mice. The TRPV1 antagonists, BCTC or theobromine, showed similar inhibitory immunologic effects on AR mice models. In addition, the number of TRPV1+/CD4+ inflammatory cells increased in the nasal mucosa of patients with AR, compared with that of control subjects. Thus, TRPV1 activation on CD4+ T cells is involved in T cell receptor signaling, and it could be a novel therapeutic target in AR.

Comparison of open dilatational tracheostomy with conventional pediatric tracheostomy in a growing animal model.

OBJECTIVES: To compare the tracheal changes after applying a new open dilatational tracheostomy (ODT) technique with those from a conventional open tracheostomy (COT) with vertical cartilage incision in a growing animal model. STUDY DESIGN: Prospective, experimental investigation in a rabbit model. MATERIALS AND METHODS: Thirteen New Zealand white rabbits as a pediatric model were divided into three groups: six rabbits had COT (n = 6), another six underwent an ODT (n = 6), and one rabbit acted as a control. Each rabbit underwent tracheostomy by assigned procedures on the first day. On day 8, they were decannulated. On day 15, their tracheas were harvested. We examined the gross findings and histologic changes of each tracheal segment at the stomal level. In addition, we analyzed three parameters: the quotient of the stomal and nonstomal segment in sagittal diameter, coronal diameter, and cross-sectional area. RESULTS: The framework of cartilages at the stomal level were more distorted in the COT group. Histologic examination also showed buckling of the anterior tracheal wall, loss of cartilage, infiltration by many polymorphonuclear neutrophils, and the marked ingrowth of fibrous tissue in the COT group. Sagittal and coronal diameters and cross-sectional areas were significantly affected more severely after a COT than after an ODT. CONCLUSION: Our new modification of percutaneous dilatational tracheostomy, named "open dilatational tracheostomy," was successfully applied to a small, growing animal model and showed more favorable and consistent healing of trachea compared with COT. Therefore, the authors' new tracheostomy procedure could be applied to children who require short-term tracheostomy at any age in clinical settings.

Prognostic factors of pediatric endoscopic sinus surgery.

OBJECTIVE: Pediatric endoscopic sinus surgery (ESS) is performed for refractory cases of rhinosinusitis that do not respond to medical management. However, few studies have been reported for the prognostic factors affecting the outcomes of pediatric ESS. The aim of this study was to investigate the prognostic factors affecting the outcomes of pediatric ESS. MATERIALS AND METHOD: Medical records of 97 pediatric patients who had undergone ESS from February 1995 to October 2003 were reviewed retrospectively. We classified the patients into two groups based on outcome, i.e., either good or poor, according to the postoperative endoscopic findings. Then univariate and multivariate analyses were performed to compare the following nine characteristics between the good and poor outcome groups: the presence of allergy, bronchial asthma, adenotonsillar hypertrophy, history of previous sinus surgery, presence of a smoker in the family, degree of polyposis, preoperative disease extent scored by CT scan findings, blood eosinophil count, and eosinophil infiltration in the nasal mucosa. RESULT: The overall success rate was 70% based on the objective postoperative endoscopic finding. Statistical differences were found between the good and poor groups in terms of the degree of preoperative polyposis and CT staging in univariate analysis, whilst in multivariate logistic regression analysis severe polyposis and indirect smoking predicted poor outcome after pediatric ESS. CONCLUSION: Pediatric ESS with severe polyposis, high CT rhinosinusitis staging, or indirect smoking predisposes to a poorer outcome. This needs to be taken into consideration when performing ESS for children.

Immunomodulatory effect of tonsil-derived mesenchymal stem cells in a mouse model of allergic rhinitis.

BACKGROUND: Although several studies have claimed that mesenchymal stem cells (MSC) derived from human tissues can ameliorate allergic airway inflammation, the immunomodulatory mechanism of MSCs remains unclear. OBJECTIVE: We aimed to determine the effects and the underlying mechanism of tonsil-derived MSCs (T-MSC) on allergic inflammation compared with adipose tissue-derived stem cells (ASC) in a mouse model of allergic rhinitis (AR). METHODS: MSCs were isolated from human palatine tonsil (T-MSC) and the surface markers were analyzed. The effect of T-MSCs was evaluated in 24 BALB/c mice that were randomly divided into four groups (negative control group, positive control group, T-MSC group, and ASC group). MSCs were administered intravenously to ovalbumin (OVA) sensitized mice (T-MSC and ASC groups) on days 18 to 23, and subsequent OVA challenge was conducted daily from days 24 to 28. Several parameters of allergic inflammation were assessed. RESULTS: T-MSC and ASC had similar characteristics in surface markers. Intravenous injection of T-MSC significantly reduced allergic symptoms, eosinophil infiltration, serum total, and OVA-specific immunoglobulin E (IgE), and the nasal and systemic T-helper (Th) 2 cytokine profile. Further analysis revealed that nasal innate cytokines, such as interleukin (IL) 25 and IL-33, and chemokines, such as CCL11, CCL24, induction was suppressed in T-MSCs injected groups, which explained their underlying mechanism. In addition, the T-MSC group had more inhibition of allergic inflammation than did the ASC group, which might be attributed to the more proliferative activity of T-MSC. CONCLUSION: Administration of T-MSC effectively reduced allergic symptoms and inflammatory parameters in the mouse model of AR. T-MSC treatment reduced Th2 cytokines and OVA-specific IgE secretion from B cells. In addition, innate cytokine (IL-25 and IL-33) expression and eotaxin messenger RNA expression was inhibited in the nasal mucosa, which is suggestive of the mechanism of reduced allergic inflammation. Therefore, T-MSC treatment is potentially an alternative therapeutic modality in AR.

Treatment outcomes of sinonasal malignant melanoma: a Korean multicenter study.

BACKGROUND: The aim of this work was to evaluate factors that influence local recurrence and survival after surgical resection of sinonasal malignant melanoma, using a large population-based multicenter study in Korea. METHODS: Retrospective analysis was performed for 155 newly diagnosed sinonasal malignant melanoma patients gathered from 15 university hospitals throughout Korea. Demographic data, tumor characteristics, surgical approach, adjuvant treatment, recurrence, and outcomes were analyzed. RESULTS: Three-year and 5-year overall survival rates were 48.8% and 40.1%, respectively. Local recurrence rate was 46.6%, with a mean recurrence time of 15.5 months. On multivariate analysis, patients who underwent surgery that included an endoscopic approach showed decreased local recurrence rate (p = 0.042) and increased survival rate (hazard ratio [HR], 1.702; 95% confidence interval [CI], 1.007 to 2.875; p = 0.047) compared to those who underwent an external approach. Patients with postoperative radiotherapy showed a decreased local recurrence rate (p = 0.001), but without impact on survival rate. Male gender, tumor beyond the nasal cavity, and presence of distant metastasis were associated with poor survival. CONCLUSION: An endoscopic-including surgical approach was associated with improved local control and survival in sinonasal malignant melanoma patients. Postoperative radiotherapy helped increase the local control rate.