Publications by authors named "David W Kennedy"

269 Publications

Comparative efficacy and safety of monoclonal antibodies and aspirin desensitization for chronic rhinosinusitis with nasal polyposis: a systematic review and network meta-analysis.

J Allergy Clin Immunol 2021 Sep 17. Epub 2021 Sep 17.

Division of Clinical Immunology and Allergy. Department of Medicine. McMaster University; Department Health Research Methods, Evidence and Impact. McMaster University; Research Institute of St. Joes Hamilton. Electronic address:

Background: Chronic rhinosinusitis with nasal polyposis (CRSwNP) is an inflammatory condition of the upper airways. Optimal management is unclear.

Objective: To compare the effects of monoclonal antibodies and ASA desensitization (ASA-D) for treatment of CRSwNP.

Methods: We searched MEDLINE, EMBASE, CENTRAL, ICTRP, FDA and EMA databases from inception to Aug 4, 2021 for RCTs comparing the effects of monoclonal antibodies and ASA-D for CRSwNP. We conducted network meta-analysis (NMA) of sinusitis symptoms, heath-related quality of life (HRQoL), rescue oral corticosteroids and surgery, endoscopic and radiologic scores, and adverse events. We used the GRADE approach to assess certainty of evidence. PROSPERO CRD42020177334.

Results: 29 RCTs evaluating 8 treatments (n=3461) were included in the NMA. Compared to placebo, moderate-high certainty evidence showed that HRQoL (SNOT-22) improved with dupilumab (MD -19.91 [95%CI -22.50, -17.32]), omalizumab (MD -16.09 [95%CI -19.88, -12.30]), mepolizumab (MD -12.89 [95%CI -16.58, -9.19], ASA-D (MD -10.61 [95% CI -14.51, -6.71]) and benralizumab (MD -7.68 [95%CI -12.09, -3.27]). The risk of rescue nasal polyp surgery likely decreased with dupilumab (RD -16.35% [95%CI -18.13, -13.48]), omalizumab (RD -7.40% [95%CI -11.04, -2.43]), mepolizumab (RD -12.33% [95%CI -15.56, -7.22]) and ASA-D (RD -16.00% [95%CI -19.79, 0.21]; all moderate certainty). Comparisons among agents show with moderate-high certainty that dupilumab ranks among the most beneficial for 7 of 7 outcomes, omalizumab for 2/7, mepolizumab for 1/7 and ASA-D for 1/7.

Conclusions: Multiple biologics and ASA-D credibly improve patient-important outcomes, with clinically important differences in effects among agents, and dupilumab uniquely ranking among the most beneficial for all outcomes studied.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jaci.2021.09.009DOI Listing
September 2021

Targeted gene expression profiling of inverted papilloma and squamous cell carcinoma.

Int Forum Allergy Rhinol 2021 Sep 12. Epub 2021 Sep 12.

Department of Otorhinolaryngology-Head and Neck Surgery, University of Pennsylvania Health System, Philadelphia, Pennsylvania, USA.

Background: Inverted papilloma (IP) is a sinonasal tumor with a well-known potential for malignant transformation. The purpose of this study was to identify the genes and pathways associated with IP, with progression to carcinoma-in-situ and invasive carcinoma.

Methods: To determine genes and molecular pathways that may indicate progression and correlate with histologic changes, we analyzed six IP without dysplasia, five IP with carcinoma-in-situ, and 13 squamous cell carcinoma ex-IP by targeted sequencing. The HTG EdgeSeq Oncology Biomarker Panel coupled with next-generation sequencing was used to evaluate 2560 transcripts associated with solid tumors.

Results: Progressive upregulation of 11 genes were observed (CALD1, COL1A1, COL3A1, COL4A2, COL5A2, FN1, ITGA5, LGALS1, MMP11, SERPINH1, SPARC) in the order of invasive carcinoma > carcinoma-in-situ > IP without dysplasia. When compared with IP without dysplasia, more genes are differentially expressed in invasive carcinoma than carcinoma-in-situ samples (341 downregulated/333 upregulated vs. 195 downregulated/156 upregulated). Gene set enrichment analysis determined three gene sets in common between the cohorts (epithelial mesenchymal transition, extracellular matrix organization, and coagulation).

Conclusions: Progressive upregulation of genes specific to IP malignant degeneration has significant clinical implications. This panel of 11 genes will improve concordance of histologic classification, which can directly impact treatment and patient outcomes. Additionally, future studies on larger tumor sets may observe upregulation in the gene panel that preceded histologic changes, which may be useful for further risk stratification.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/alr.22882DOI Listing
September 2021

Pre-intervention SNOT-22 scores predict outcomes in aspirin exacerbated respiratory disease.

Am J Otolaryngol 2021 Sep-Oct;42(5):103025. Epub 2021 Mar 31.

Department of Otorhinolaryngology-Head and Neck Surgery, University of Pennsylvania, Philadelphia, PA, United States of America.

Purpose: This study evaluated whether stratified preoperative, pre- aspirin desensitization (AD) sinonasal symptom scores predict postoperative, post-AD outcomes in Aspirin exacerbated respiratory disease (AERD).

Materials And Methods: Retrospective chart review of patients with aspirin challenge-proven AERD who underwent endoscopic sinus surgery followed by AD was performed. Preoperative, postoperative/pre-AD, and postoperative/post-AD sinonasal symptom scores were collected (22-item Sino-Nasal Outcomes Test, SNOT-22). A longitudinal linear mixed-effects model was used for data analysis.

Results: Forty-seven patients (59.6% female) aged 48.0 ± 13.2 were included. Average time from surgery to AD was 70.0 ± 52.8 days. Preoperative SNOT-22 scores (n = 47) were divided into tertiles (cutoffs of 36 and 54 indicating mild [22.5 ± 13.7], moderate [44.3 ± 12.2], and severe [72.9 ± 19.7] disease). This corresponded to 12 (25.5%), 18 (38.3%), and 17 (36.2%) subjects being categorized into mild, moderate, and severe tertiles, respectively. Postoperative, pre-AD SNOT-22 in all disease groups decreased and were not significantly different (12.3 ± 13.7, 11.1 ± 12.2, 22.7 ± 19.7; p = 0.074). At short-term post-AD, only the severe group worsened (35.0 ± 20.3, p < 0.001), whereas other groups demonstrated negligible change (9.3 ± 14.3 and 14.4 ± 12.2). At long-term post-AD, all groups redemonstrated convergence in symptom scores (23.7 ± 20.9, 19.4 ± 15.4, and 31.0 ± 27.6, p = 0.304).

Conclusion: Preoperative SNOT-22 scores may be used as a predictor of postoperative, post-AD patient-reported outcomes in AERD. Patients with mild and moderate disease may derive benefit from surgery and AD alone, while those with severe disease may require additional interventions (e.g., biologics).
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.amjoto.2021.103025DOI Listing
March 2021

Treatment Outcomes in Aspirin-Exacerbated Respiratory Disease Based on the 12-Item Short Form Survey.

Am J Rhinol Allergy 2021 Mar 10:19458924211001640. Epub 2021 Mar 10.

Department of Otorhinolaryngology-Head and Neck Surgery, University of Pennsylvania, Philadelphia, Pennsylvania.

Background: Aspirin-exacerbated respiratory disease (AERD) is optimally managed by endoscopic sinus surgery (ESS) followed by aspirin therapy after desensitization (ATAD). Most AERD quality of life (QOL) studies use the 22-item Sinonasal Outcomes Test (SNOT-22), which focuses predominantly on sinonasal outcomes.

Objective: This study seeks to assess QOL outcomes in AERD patients after ESS and ATAD via the 12-item Short Form Survey (SF-12), a well-validated QOL measure for general health status of chronic conditions.

Methods: Retrospective review of 112 AERD patients who underwent ESS followed by ATAD at our institution between 2016 and 2019. SF-12 was collected preoperatively, postoperatively/pre-AD, and serially post-AD (1-3, 4-6, 7-12, and >12 months). Optum® PRO CoRE software was used to compare data to national norms. ANOVA was performed comparing physical component summary (PCS), mental component summary (MCS) and eight health domains (physical functioning, role physical, general health, bodily pain, vitality, social functioning, role emotional, and mental health).

Results: AERD patients showed improvement in PCS scores across all timepoints after ESS and ATAD (p = 0.004). When stratified by gender, women demonstrated an improvement in PCS scores (p = 0.004). Within the domains, there were significant improvements in social functioning (SF), role physical (RP), and bodily pain (BP) at all timepoints (SF: p = 0.006; RP: p = 0.005; BP: p < 0.001).

Conclusions: AERD patients undergoing ESS and ATAD show improvement in physical QOL and 3 of the 8 health domains as measured by the SF-12. Future studies can use the SF-12 to study the impact of AERD treatment versus other chronic diseases and health demographics.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1177/19458924211001640DOI Listing
March 2021

Effectiveness of endoscopic sinus surgery and aspirin therapy in the management of aspirin-exacerbated respiratory disease.

Allergy Asthma Proc 2021 03;42(2):136-141

Department of Otorhinolaryngology, University of Pennsylvania, Philadelphia, Pennsylvania; and.

Aspirin therapy and/or type 2 (T2) biologics are used in the management of aspirin-exacerbated respiratory disease (AERD). To identify the number of patients with AERD who tolerated aspirin therapy, yet due to persistent symptoms, incorporated T2 biologic management. A retrospective review was performed between July 2016 and June 2019. Patients with AERD and who underwent endoscopic sinus surgery (ESS), aspirin desensitization (AD), and at least 6 months of aspirin therapy (ATAD) after AD, and who remained biologic-naive up through this timepoint were included in the study. Introduction of a T2 biologic while on ATAD was the primary outcome. The secondary outcome was a change in a validated patient-reported outcome measure for chronic rhinosinusitis score between the postoperative predesensitization timepoint, and the 6-month postdesensitization timepoint, presented as means and compared by using the Student's t-test. A total of 103 patients met inclusion criteria. Two patients (1.9%) ultimately supplemented ATAD with a T2 biologic. The mean outcomes measure test score after 6 months of ATAD for patients who received biologics was 40.5 versus 15 in those who did not receive biologics (p = 0.02). The mean differences between the postoperative predesensitization test score and the 6-month postdesensitization test score for patients who went on to receive biologics was an increase of 13 versus a decrease of 10 for those patients who did not receive biologics (p = 0.12). ESS, coupled with AD and ATAD, was successful in the long-term management of the majority of the patients with AERD, which rarely required the incorporation of T2 biologics. Patient questionnaires, such as outcomes measure test score, may identify aspirin therapy failures and help guide the practitioner in deciding when to introduce T2 biologics into the patient's treatment regimen.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.2500/aap.2021.42.210002DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8133012PMC
March 2021

Multidisciplinary single-center outcomes compared to two-center outcomes for the treatment of aspirin exacerbated respiratory disease.

J Allergy Clin Immunol Pract 2021 06 3;9(6):2498-2500. Epub 2021 Feb 3.

Division of Rhinology, Department of Otorhinolaryngology, Head and Neck Surgery, University of Pennsylvania, Perelman School of Medicine, Philadelphia, Pa.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jaip.2021.01.032DOI Listing
June 2021

Solitary chemosensory cells are innervated by trigeminal nerve endings and autoregulated by cholinergic receptors.

Int Forum Allergy Rhinol 2021 05 11;11(5):877-884. Epub 2020 Oct 11.

Division of Rhinology, Department of Otorhinolaryngology-Head and Neck Surgery, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA.

Background: Solitary chemosensory cells (SCCs) in the murine nasal epithelium are discrete specialized cells that respond to irritants and activate trigeminal nerve fibers through the release of acetylcholine (ACh), resulting in local neurogenic inflammation. In addition to releasing ACh, SCCs are the exclusive epithelial source of interleukin (IL)-25. In humans, SCCs are significantly expanded in sinonasal polyps (NPs). However, the SCC-trigeminal synapse has yet to be demonstrated in human sinonasal epithelium.

Methods: Immunofluorescence for trigeminal nerve fiber markers, nicotinic ACh receptors (nChR), and SCC markers was performed in vibratome sections from polyp and healthy turbinate tissue. Quantitative polymerase chain reaction and immunofluorescence of cultured epithelial cells were used to evaluate the expansion of SCCs. Last, intracellular calcium imaging was used to demonstrate cholinergic signaling in sinonasal epithelial cells.

Results: Calcitonin gene-related peptide (CGRP) immunostaining was used to identify cholinergic nerve endings, which were only evident in sections from the inferior turbinate and intertwined with SCCs (α-gustducin-positive cells). CGRP-positive nerve endings were not identified in sections from NPs. Human SCCs expressed nChR as well as the ACh synthetic enzyme choline acetyltransferase. Live cell calcium imaging demonstrated functionally active cholinergic signaling in discrete sinonasal epithelial cells, consistent with SCCs. Finally, SCC-specific genes were dramatically upregulated with pretreatment with IL-13 and nicotinic agonists.

Conclusion: SCCs are innervated by trigeminal nerve endings in healthy turbinate tissue but not in NPs. SCCs express ACh receptors as well as choline acetyltransferase and, in the setting of a type 2 inflammatory environment, denervated SCCs dramatically expand with nicotinic stimulation.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/alr.22695DOI Listing
May 2021

Divergent bitter and sweet taste perception intensity in chronic rhinosinusitis patients.

Int Forum Allergy Rhinol 2021 05 26;11(5):857-865. Epub 2020 Aug 26.

Monell Chemical Senses Center, Philadelphia, PA.

Background: Bitter and sweet taste receptors are present in the human upper airway, where they have roles in innate immunity. Previous studies have shown that 1 of the 25 bitter receptors, TAS2R38, responds to specific bacterial signaling molecules and evokes 1 type of a defense response in the upper airway, whereas ligands of sweet receptors suppress other types of defense responses.

Methods: We examined whether other bitter taste receptors might also be involved in innate immunity by using sensory responses to bitter compounds that are not ligands of TAS2R38 (quinine and denatonium benzoate) to assess the sensitivity of other bitter receptors in chronic rhinosinusitis (CRS) patients. CRS patients with (n = 426) and without (n = 226) nasal polyps and controls (n = 356) rated the intensity of quinine, denatonium benzoate, phenylthiocarbamide (PTC; a ligand for TAS2R38), sucrose, and salt.

Results: CRS patients rated the bitter compounds denatonium benzoate and quinine as less intense and sucrose as more intense than did controls (false discovery rate [FDR] <0.05) and CRS patients and controls did not differ in their ratings of salt (FDR >0.05). PTC bitter taste intensity differed between patient and control groups but were less marked than those previously reported. Though differences were statistically significant, overall effect sizes were small.

Conclusion: CRS patients report bitter stimuli as less intense but sweet stimuli as more intense than do control subjects. We speculate that taste responses may reflect the competence of sinonasal innate immunity mediated by taste receptor function, and thus a taste test may have potential for clinical utility in CRS patients.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/alr.22686DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7907256PMC
May 2021

Guidance for contemporary use of biologics in management of chronic rhinosinusitis with nasal polyps: discussion from a National Institutes of Health-sponsored workshop.

Int Forum Allergy Rhinol 2020 09 3;10(9):1037-1042. Epub 2020 Jul 3.

Department of Otolaryngology, Head and Neck Surgery, McGovern Medical School, University of Texas Health Science Center at Houston, Houston, TX.

Background: Biologic medications are emerging as options for treating chronic rhinosinusitis with nasal polyps (CRSwNP). Several questions remain regarding patient selection, indications, clinical efficacy, and cost effectiveness.

Methods: In November 2019, a group of physicians and scientists gathered to consider strategies for future studies regarding biologics. During the discussion, gaps in knowledge highlighted a need for a consensus on the present day use of biologics in polyp patients.

Results: The goal of this guideline is to propose recommendations for the current use of biologics in CRSwNP as new evidence continues to emerge and inform practice.

Conclusion: We suggest that physicians evaluate patients on an individual basis and closely monitor for improvement due to the high cost and unknown long-term effects of biologics.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/alr.22633DOI Listing
September 2020

The current status of the sinonasal microbiome and the role of topical probiotics.

Authors:
David W Kennedy

Int Forum Allergy Rhinol 2020 04;10(4):431-432

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/alr.22563DOI Listing
April 2020

Management of the visual field in endoscopic sinus surgery.

Authors:
David W Kennedy

Int Forum Allergy Rhinol 2020 02;10(2):139-140

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/alr.22527DOI Listing
February 2020

In vitro safety of ketotifen as a topical nasal rinse.

Int Forum Allergy Rhinol 2020 02;10(2):265-270

Department of Otorhinolaryngology-Head and Neck Surgery, University of Pennsylvania, Philadelphia, PA.

Background: Ketotifen is a second-generation noncompetitive H1-antihistamine and mast-cell stabilizer. It is commonly used to treat or prevent allergic conjunctivitis, asthma, chronic urticaria, anaphylaxis, mast-cell, and other allergic-type disorders. However, it has never been studied in aspirin-exacerbated respiratory disease (AERD), an aggressive phenotype of chronic rhinosinusitis with nasal polyps, where the mast cell plays a prominent role its pathogenesis.

Methods: Human sinonasal epithelial cells were grown at an air-liquid interface (ALI). Ketotifen powder was dissolved in saline to make 4 test solutions at 1.04, 2.08, 10.4, and 20.8 µg/mL. Control (saline) or ketotifen solution was added apically to ALI cultures from tissue of 5 unique patients, and ciliary beat frequency (CBF) changes were recorded. Lactate dehydrogenase was measured at 24 and 48 hours to estimate long-term cellular toxicity.

Results: Apical application of ketotifen at all concentrations was neither ciliotoxic nor ciliostimulatory, with no change in CBF over a period of 15 minutes after application. Cellular toxicity for all concentrations at 24 and 48 hours after application was <3% and <7%, respectively, that of lysed cultures.

Conclusion: Topical application of ketotifen to an in vitro model of sinonasal epithelium is safe, as evaluated by CBF and lactate dehydrogenase. Ketotifen is neither ciliotoxic nor ciliostimulatory, and no long-term cellular toxicity was observed. Ketotifen may have promise as a topical nasal rinse in the treatment of AERD.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/alr.22461DOI Listing
February 2020

Inverted papilloma is associated with greater radiographic inflammatory disease than other sinonasal malignancy.

Int Forum Allergy Rhinol 2020 03 5;10(3):278-281. Epub 2020 Feb 5.

Department of Otorhinolaryngology-Head and Neck Surgery, University of Pennsylvania, Philadelphia, PA.

Background: The pathogenesis of inverted papilloma (IP) has not been fully elucidated. However, chronic paranasal sinus inflammation has been anecdotally observed in sites distant from tumor obstruction in IP patients, suggesting an association between inflammation and IP tumorigenesis. This study assesses the association between sinonasal inflammation found in IP and compares this to the level of inflammation observed in other sinonasal tumors.

Methods: A retrospective chart review was performed identifying patients with unilateral IP. Pertinent clinical data was obtained and comparative analysis of preoperative computed tomography (CT) imaging and histopathology was performed. A sample of unilateral, sinonasal, non-IP and non-squamous cell tumors was used as the control. The Lund-Mackay scoring system was used to assess radiologic sinonasal inflammation both ipsilateral and contralateral to the tumor.

Results: Seventy-one patients were included; 58.9% of patients with IP had evidence of contralateral sinusitis at the time of presentation. In the control group, 26.7% had evidence of contralateral inflammation. When comparing contralateral sinus inflammation between the 2 study groups, the IP patients had significantly higher Lund-Mackay scores than the control group (1.9 vs 0.26, p < 0.001). When comparing ipsilateral sinus inflammation, no significant difference was found in Lund-Mackay scores (5.44 vs 4.00, p < 0.184).

Conclusion: In this study, unilateral IPs were associated with a higher level of contralateral sinonasal inflammation when compared to control. This suggests that IP may be associated with inflammation that is independent of obstruction by the tumor. Further studies are needed to better understand the temporal relationship between chronic inflammation and tumorigenesis.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/alr.22484DOI Listing
March 2020

Distinct temporal diversity profiles for nitrogen cycling genes in a hyporheic microbiome.

PLoS One 2020 27;15(1):e0228165. Epub 2020 Jan 27.

Pacific Northwest National Laboratory, Richland, Washington, United States of America.

Biodiversity is thought to prevent decline in community function in response to changing environmental conditions through replacement of organisms with similar functional capacity but different optimal growth characteristics. We examined how this concept translates to the within-gene level by exploring seasonal dynamics of within-gene diversity for genes involved in nitrogen cycling in hyporheic zone communities. Nitrification genes displayed low richness-defined as the number of unique within-gene phylotypes-across seasons. Conversely, denitrification genes varied in both richness and the degree to which phylotypes were recruited or lost. These results demonstrate that there is not a universal mechanism for maintaining community functional potential for nitrogen cycling activities, even across seasonal environmental shifts to which communities would be expected to be well adapted. As such, extreme environmental changes could have very different effects on the stability of the different nitrogen cycle activities. These outcomes suggest a need to modify existing conceptual models that link biodiversity to microbiome function to incorporate within-gene diversity. Specifically, we suggest an expanded conceptualization that 1) recognizes component steps (genes) with low diversity as potential bottlenecks influencing pathway-level function, and 2) includes variation in both the number of entities (e.g. species, phylotypes) that can contribute to a given process and the turnover of those entities in response to shifting conditions. Building these concepts into process-based ecosystem models represents an exciting opportunity to connect within-gene-scale ecological dynamics to ecosystem-scale services.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0228165PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6984685PMC
April 2020

Aspirin exacerbated respiratory disease (AERD) treatment revisited.

Authors:
David W Kennedy

Int Forum Allergy Rhinol 2019 12;9(12):1399-1400

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/alr.22496DOI Listing
December 2019

Chronic rhinosinusitis precipitated by tumor necrosis factor alpha inhibitors is the phenotype of chronic rhinosinusitis without nasal polyps.

Int Forum Allergy Rhinol 2020 01 3;10(1):23-28. Epub 2019 Dec 3.

Department of Otorhinolaryngology-Head and Neck Surgery, University of Pennsylvania, Philadelphia, PA.

Background: Chronic rhinosinusitis (CRS) is a frequently observed condition in patients with immunodeficiency secondary to tumor necrosis factor alpha inhibitors (TNFαis). The histologic features of CRS caused by TNFαis have yet to be determined and may have important implications in understanding the pathophysiology of the disease process.

Methods: A structured histopathology report was used to analyze sinus tissue removed during functional endoscopic sinus surgery (FESS). These structured histopathology variables were compared among patients with CRS on TNFαi (CRSαi), CRS without nasal polyps (CRSsNP) patients, and CRS with nasal polyps (CRSwNP) patients.

Results: Eighteen CRSαi, 91 CRSwNP, and 113 CRSsNP patients undergoing FESS were analyzed. Compared to CRSsNP, CRSαi patients exhibited increased mucosal ulceration (16.7% vs 0.9%, p < 0.008), increased fibrosis (100% vs 34.5%, p < 0.001), and increased presence of Charcot-Leiden crystals (16.7% vs 0%, p < 0.002). Compared to CRSwNP, CRSαi patients demonstrated increased fibrosis (100% vs 54.9%, p < 0.001), decreased presence of subepithelial edema (44.4% vs 69.2% p < 0.043), decreased eosinophil aggregates (22.2% vs 47.3% p < 0.042), and fewer eosinophils per high-power field (44.4% vs 73.6%, p < 0.017).

Conclusion: CRSαi exhibits structured histopathology more similar to CRSsNP. In the appropriate clinical context, it may be reasonable that the medical regimen for these patients be focused on a more antineutrophilic, macrolide-based approach. This study provides insight into the inflammatory environment of patients with CRSαi and may have implications for disease management.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/alr.22462DOI Listing
January 2020

Clinical Implications of Carcinoma In Situ in Sinonasal Inverted Papilloma.

Otolaryngol Head Neck Surg 2019 12 22;161(6):1036-1042. Epub 2019 Oct 22.

Department of Otorhinolaryngology-Head & Neck Surgery, University of Pennsylvania Health System, Philadelphia, Pennsylvania, USA.

Objective: Sinonasal inverted papilloma (IP) is a typically benign sinonasal tumor with a tendency to recur and the potential for malignant transformation. Varying degrees of dysplasia may be present, of which carcinoma in situ (CIS) is most advanced. We hereby describe the biological and clinical behavior of IP with CIS (IPwCIS).

Study Design: Retrospective cohort.

Setting: Tertiary academic referral center.

Subjects And Methods: Patients who underwent surgical resection for IP between 2002 and 2017. Pertinent clinical data were obtained, and all IPwCIS cases were histologically confirmed.

Results: In total, 37 of 215 cases (17.2%) were identified with IPwCIS. Mean age was 57 years and 86.5% of patients were male. Median follow-up was 82 months, and the recurrence rate was 27%. The maxillary sinus was the most common primary site (37.8%) and 14 tumors (37.8%) demonstrated multifocal attachment, which was associated with recurrence (odds ratio [OR], 9.7; 95% confidence interval [CI], 1.4-112.8; = .028). IPwCIS was also associated with multiple recurrences (OR, 2.71; 95% CI, 1.246-5.814; = .021). Most patients were treated with surgery alone (89.1%) and 4 patients received adjuvant radiotherapy (8.1%). Only 1 patient (2.7%) demonstrated malignant transformation after definitive surgery.

Conclusions: IPwCIS represents the most severe degree of dysplasia prior to malignant transformation and is associated with higher recurrence rate and multifocal involvement but low rate of conversion to invasive carcinoma. The need for adjuvant therapy remains controversial, and further research into the etiology of the disease is warranted.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1177/0194599819883298DOI Listing
December 2019
-->