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Simple Summary: Patients with pituitary tumors and other masses at the bottom of the skull are at risk of brain infection and leaks of the fluid surrounding the brain when the tumor is removed surgically. To prevent these types of complications, surgeons have developed techniques to patch the surgical area with normal tissue taken from other parts of the body. In the past, this tissue was taken from the head, neck, and shoulder regions. Newer techniques allow the entire surgery to occur within the nose, resulting in fewer side effects and faster recovery. This includes taking normal tissue from within the nose to repair the base of the skull where the mass is removed. The nasoseptal flap is the most common method for this type of intranasal repair. In this paper, we describe the development and evolution of this surgical technique and discuss the impact that it has had on patient outcomes. The nasoseptal flap is a workhorse reconstructive option for anterior skull base defects during endonasal surgery. This paper highlights the versatility of the nasoseptal flap. After providing a brief historical perspective, this review will focus on the relevant primary literature published in the last ten years. We will touch upon new applications of the flap, how the flap has been modified to expand its reach and robustness, and some of the current limitations. We will conclude by discussing what the future holds for improving upon the design and use of the nasoseptal flap in anterior skull base reconstruction. [ABSTRACT FROM AUTHOR]

Background: The extended endonasal approach has been utilized in the resection of anterior skull base lesions in the pediatric population. There are unique challenges to these patients in the post‐operative setting, including patient compliance with medical therapy and post‐operative debridements, and a smaller nasal airway that may increase propensity toward scarring. Our objective for this study is to evaluate the incidence of post‐operative radiographic inflammation in this patient population using the Lund‐Mackay (LM) score. Methods: A single‐center, retrospective review of pediatric patients undergoing endoscopic approach to the skull base between 2009 and 2021 was performed. Demographic and clinicopathologic data and pre‐ and post‐operative imaging were analyzed. One‐way ANOVA followed by Tukey multiple pairwise comparisons statistical tests were used to compare mean LM scores between groups. Results: Seventy‐two patients (52 males, 20 females) were identified with a median follow‐up of 27 months. All patients underwent an extended endonasal approach for resection of skull base lesions. The mean LM scores were compared between pre‐operative MRI, first post‐operative MRI > 30 days after surgery, and most recent post‐operative MRI. One‐way ANOVA was performed with significant differences noted between the groups (p < 0.001). Tukey multiple pairwise comparisons test was then performed and noted significant differences between the pre‐operative and first post‐operative LM (p < 0.0001) and the first post‐operative and most recent LM (p < 0.0001). There was no significant difference noted between the pre‐operative LM score and most recent LM score (p = 0.14). Conclusion: Despite concerns regarding possible subsequent development of chronic rhinosinusitis following endoscopic skull base surgery in pediatric patients, the current study suggests that transient radiographic evidence of sinus inflammation can be seen up to six months postoperatively, which appears to resolve by approximately two years after surgery. Level of Evidence: 4 Laryngoscope, 133:2014–2017, 2023 [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Objective  Surgical resection is widely accepted as a critical component for definitive treatment of sinonasal mucosal melanoma. Systemic immunotherapy, including multiple newer agents, has been used to treat metastatic or unresectable disease. In this study, we examine its efficacy in locoregional control when used in conjunction with surgical resection for primary mucosal lesions. Design  Present study is a retrospective review of all patients at a tertiary academic medical center with primary sinonasal mucosal melanoma and distant metastatic disease. Results  A total of four patients were identified. In all cases, patients were treated with a combination of surgical resection of the primary tumor and systemic immunotherapy. Three patients were initially treated with surgery at the primary site followed by immunotherapy for distant metastases. Response to immunotherapy at the sites of primary and metastatic disease was seen in two patients. All four patients developed progression or recurrence at the primary site following initiation of immunotherapy for which they underwent surgical resection. One patient remains in follow-up without evidence of disease 20 months after initial treatment; three succumbed to the disease at 135, 37, and 16 months after initial treatment. Conclusion  Surgical resection for local control plays a critically important role in the treatment of sinonasal mucosal melanoma regardless of the presence of metastases and whether immunotherapy will be given. This case series suggests that, though immunotherapy may demonstrate efficacy in managing distant disease, surgery should remain the first-line treatment for the primary site. [ABSTRACT FROM AUTHOR]

Objectives  A persistent craniopharyngeal canal (CPC) is a rare embryologic remnant that presents as a well-corticated defect of the midline sphenoid body extending from the sellar floor to the nasopharynx. Our case series aims to describe three unique presentations of this congenital anomaly and their subsequent management. Design  Retrospective review. Setting  Tertiary academic medical center. Participants  Patients who underwent endoscopic transnasal surgical repair of a CPC lesion. Main Outcome Measures  Resolution of symptoms and surgical outcomes. Results  A total of three patients were identified. The clinical presentation varied, however, all cases prompted further imaging which demonstrated a persistent CPC and associated pathologic lesion. The presentation of a persistent CPC with nasal obstruction and subsequent iatrogenic cerebrospinal fluid leak as in Case 1 demonstrates the importance of imaging in this work-up. Cases 2 and 3 in the series were representative of the larger subset of patients in the literature who present with the defect incidentally but still warrant surgical management. Nonetheless, a standard approach to diagnosis with preoperative imaging and subsequent transnasal endoscopic repair of the skull base defect was undertaken. Conclusion  The persistent CPC is a rare congenital anomaly associated with diverse pathology and careful review of preoperative radiology is critical to the management. When warranted, subsequent surgical repair and reconstruction is associated with excellent postoperative outcomes. [ABSTRACT FROM AUTHOR]

Objectives/hypothesis: Currently, due to the rarity of pathology, there are limited data surrounding outcomes of pediatric skull base surgery. Traditionally, surgeons have proceeded with caution when electing endonasal endoscopic transsellar/transplanum approaches to the skull base in pediatric patients due to poor sphenoid pneumatization. In this study, we review outcomes of endoscopic pediatric skull base surgery based on sphenoid pneumatization patterns.Study Design: Retrospective chart review.Methods: A review of all cases of pediatric (age < 18 years) craniopharyngioma managed via an endoscopic endonasal approach at a tertiary academic medical center.Results: A total of 27 patients were included in the analysis. The median age was 8 years. Nineteen (70%) patients were male. Presellar, sellar/postsellar, and conchal sphenoid pneumatizations were found in 6, 11, and 10 patients, respectively. There was no significant association between sphenoid pneumatization pattern and extent of resection (gross vs. subtotal, P = .414), postoperative cerebrospinal fluid (CSF) leak (P = .450), intraoperative estimated blood loss (P = .098), total operative time (P = .540), and length of stay (P = .336). On multivariate analysis, after accounting for age, sex, preoperative cranial nerve involvement, and cavernous sinus invasion, there remained no significant association between sphenoid pneumatization pattern and extent of resection (P = .999) and postoperative CSF leak (P = .959).Conclusions: Sphenoid pneumatization pattern does not appear to affect outcomes in endoscopic skull base surgery in the pediatric population. Importantly, lack of sphenoid pneumatization does not impede gross total resection or increase complications. Thorough knowledge of the anatomy during the endoscopic approach is critical to optimize outcomes.Level Of Evidence: 4 Laryngoscope, 129:832-836, 2019. [ABSTRACT FROM AUTHOR]

Objectives/hypothesis: Inverted papillomas (IPs) are benign tumors of the sinonasal tract with a malignant transformation potential. Predicting the transformation propensity of IPs and corresponding risk factors has long been a challenge. In this study, we aimed to use radiographic findings on magnetic resonance imaging (MRI) and computed tomography (CT) to help differentiate IP from IP-transformed squamous cell carcinomas (IP-SCC).Study Design: Retrospective cohort study.Methods: A retrospective analysis was performed at two institutions comparing IP (n = 76) and IP-SCC (n = 66) tumors, evaluating preoperative radiographic imaging with corresponding surgical pathology reports. The presence of a convoluted cerebriform pattern (CCP) using postcontrast T1-weighted and T2-weighted MRI was evaluated. Using MRI diffusion-weighted imaging (DWI), we calculated the apparent diffusion coefficient (ADC) value of each tumor. We also determined the tumor origin, attachment sites, and presence of bony erosion using CT imaging.Results: Benign IPs had a higher prevalence of CCP on MRI compared to IP-transformed SCC (P = .0001. The mean value ADC of malignant IP-SCC (ADCb0,1000  = 1.12 × 10-3 mm2 /s) was significantly lower than that of benign IPs (ADCb0,1000  = 1.49 × 10-3 mm2 /s, P = .002). IP-SCC tumors were more likely to be have orbital wall attachment (P = .002) and bony erosion (P < .0001) compared to IPs.Conclusions: Evaluation of CCP and DWI with ADC values on MRI are promising qualitative and quantitative methods to help differentiate benign IP tumors from their transformed malignant counterparts. Malignant IP-SCCs are associated with a loss of CCP and lower ADC values. Findings of orbital wall involvement and bony erosion on CT may also help determine presence of malignancy.Level Of Evidence: 4 Laryngoscope, 129:777-782, 2019. [ABSTRACT FROM AUTHOR]

Background Methods Results Conclusions Cystic fibrosis transmembrane conductance regulator (CFTR) modulators improve pulmonary outcomes in cystic fibrosis (CF) by stabilizing the CFTR protein on respiratory epithelial surfaces. To determine the efficacy of CFTR modulators on sinonasal outcomes in patients with CF, we performed a meta‐analysis of clinical trials to date that include functional and radiographic evidence of sinus disease.English full‐text articles were searched in PubMed, Embase, and Scopus databases. Two reviewers screened articles and a third reviewer resolved disagreements. Articles were included if they reported functional or radiological sinonasal outcomes in patients with CF before and after CFTR modulator therapies. Preferred Reporting Items for Systematic Reviews and Meta‐Analyses guidelines were followed, and the risk of bias in non‐randomized studies of interventions tool was used for quality assessment. The generic inverse variance method with random effects model was used for meta‐analysis. Standardized mean difference (SMD) and mean difference (MD) were used as effect measurements.Seven prospective and two retrospective studies representing 248 patients were included in this analysis. There was a significant improvement in sinonasal outcome test‐22 scores on elexacaftor‒tezacaftor‒ivacaftor (MD = 12.80, [95% confidence interval, CI: 10.46‒15.13], p < 0.001, n = 222), with no heterogeneity detected (I2 = 0%, p = 0.820). There was also a significant improvement in Lund‒Mackay scores (SMD = 1.25, [95% CI: 0.58‒1.91], p < 0.001, n = 88), with heterogeneity detected (I2 = 67%, p = 0.030).CFTR modulators improve functional and radiologic sinonasal outcomes. Given the utility of CFTR modulators, the treatment paradigm for CF‐related chronic rhinosinusitis promises to evolve. [ABSTRACT FROM AUTHOR]

Background Methods Results Conclusion Inverted papilloma (IP) is a benign tumor characterized by epithelial proliferation, which has the potential for malignant transformation. However, the mechanisms driving this transformation are poorly defined. Matrix metalloproteinase‐11 (MMP‐11), a regulator of the tumor microenvironment that degrades extracellular matrix, is upregulated in IP with dysplasia. Here, we aim to investigate the role of MMP‐11 in IP epithelial migration and invasion.Human IP and contralateral normal sinus mucosa (control) samples were obtained. IP‐derived epithelial cultures and normal mucosa‐derived epithelial cultures were grown in air‒liquid interface, followed by immunostaining to assess MMP‐11 expression in IP. Migration and invasion assays were used to evaluate the role of an anti‐MMP‐11 antibody on IP and control epithelial cultures.IP‐derived cultures demonstrated strong MMP‐11 expression compared to controls. Treatment with anti‐MMP‐11 blocking antibody significantly reduced epithelial migration only in IP‐derived cells compared to non‐treated IP cells, as seen by incomplete wound closure and reduced transepithelial resistance. In addition, inhibition of MMP‐11 reduced IP epithelia's ability to invade through collagen‐coated transwells, suggesting that MMP‐11 plays a role in invasion.We established an in vitro model to study IP‐derived epithelial cells. MMP‐11 is uniquely expressed in IP epithelial cultures compared to control epithelial cultures. Inhibition of MMP‐11 limits IP epithelial migration and invasion to levels similar to that of normal sinus mucosa. MMP‐11 does not appear to have a functional role in normal sinus epithelium, suggesting that MMP‐11 has a role in malignant transformation of IP. [ABSTRACT FROM AUTHOR]

Objectives: There is growing interest in assessing patient quality of life (QOL) following treatment of sinonasal tumors, including inverted papilloma (IP). We aimed to elucidate the natural history of postoperative QOL outcomes in IP patients treated with surgery., Methods: Cases of sinonasal IP treated surgically at 4 tertiary academic rhinology centers were retrospectively reviewed. SNOT-22 scores were used to evaluate QOL preoperatively and postoperatively (1, 3, 6, 12 months). Repeated-measures ANOVA assessed for differences in mean scores over time. Linear regression identified factors associated with QOL longitudinally., Results: 373 patients were analyzed. Mean preoperative SNOT-22 score was 20.6 ± 20.4, which decreased to 16.3 ± 18.8 (p = 0.041) and 11.8 ± 15.0 (p < 0.001) at 1 and 3 months postoperatively, respectively. No further changes in SNOT-22 scores occurred beyond 3 months postoperatively (p > 0.05). When analyzed by SNOT-22 subdomains, nasal, sleep, and otologic/facial subdomain scores (all p < 0.05) demonstrated improvement at 12-month follow-up compared with preoperative scores; this was not observed for the emotional subdomain score (p = 0.800). Recurrent cases were associated with higher long-term SNOT-22 scores (β = 7.08; p = 0.017). Age, sex, degree of dysplasia, prior surgery, primary site, and smoking history did not correlate with symptoms (all p > 0.05)., Conclusions: QOL outcomes related to IP resection are largely driven by nasal, sleep, and otologic/facial subdomains, though patients appear to experience enduring improvement as early as 3 months postoperatively. Recurrent disease is a major driver of negative QOL., Level of Evidence: 4 Laryngoscope, 2024., (© 2024 The Author(s). The Laryngoscope published by Wiley Periodicals LLC on behalf of The American Laryngological, Rhinological and Otological Society, Inc.)

Background: Sinonasal neoplasms, whether benign and malignant, pose a significant challenge to clinicians and represent a model area for multidisciplinary collaboration in order to optimize patient care. The International Consensus Statement on Allergy and Rhinology: Sinonasal Tumors (ICSNT) aims to summarize the best available evidence and presents 48 thematic and histopathology-based topics spanning the field., Methods: In accordance with prior International Consensus Statement on Allergy and Rhinology documents, ICSNT assigned each topic as an Evidence-Based Review with Recommendations, Evidence-Based Review, and Literature Review based on the level of evidence. An international group of multidisciplinary author teams were assembled for the topic reviews using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses format, and completed sections underwent a thorough and iterative consensus-building process. The final document underwent rigorous synthesis and review prior to publication., Results: The ICSNT document consists of four major sections: general principles, benign neoplasms and lesions, malignant neoplasms, and quality of life and surveillance. It covers 48 conceptual and/or histopathology-based topics relevant to sinonasal neoplasms and masses. Topics with a high level of evidence provided specific recommendations, while other areas summarized the current state of evidence. A final section highlights research opportunities and future directions, contributing to advancing knowledge and community intervention., Conclusion: As an embodiment of the multidisciplinary and collaborative model of care in sinonasal neoplasms and masses, ICSNT was designed as a comprehensive, international, and multidisciplinary collaborative endeavor. Its primary objective is to summarize the existing evidence in the field of sinonasal neoplasms and masses., (© 2023 The Authors. International Forum of Allergy & Rhinology published by Wiley Periodicals LLC on behalf of American Academy of Otolaryngic Allergy and American Rhinologic Society.)

The nasoseptal flap is a workhorse reconstructive option for anterior skull base defects during endonasal surgery. This paper highlights the versatility of the nasoseptal flap. After providing a brief historical perspective, this review will focus on the relevant primary literature published in the last ten years. We will touch upon new applications of the flap, how the flap has been modified to expand its reach and robustness, and some of the current limitations. We will conclude by discussing what the future holds for improving upon the design and use of the nasoseptal flap in anterior skull base reconstruction.

Background: Distinguishing benign inverted papilloma (IP) tumors from those that have undergone malignant transformation to squamous cell carcinoma (IP-SCC) is important but challenging to do preoperatively. Magnetic resonance imaging (MRI) can help differentiate these 2 entities, but no established method exists that can automatically synthesize all potentially relevant MRI image features to distinguish IP and IP-SCC. We explored a deep learning approach, using 3-dimensional convolutional neural networks (CNNs), to address this challenge., Methods: Retrospective chart reviews were performed at 2 institutions to create a data set of preoperative MRIs with corresponding surgical pathology reports. The MRI data set included all available MRI sequences in the axial plane, which were used to train, validate, and test 3 CNN models. Saliency maps were generated to visualize areas of MRIs with greatest influence on predictions., Results: A total of 90 patients with IP (n = 64) or IP-SCC (n = 26) tumors were identified, with a total of 446 images of distinct MRI sequences for IP (n = 329) or IP-SCC (n = 117). The best CNN model, All-Net, demonstrated a sensitivity of 66.7%, specificity of 81.5%, overall accuracy of 77.9%, and receiver-operating characteristic area under the curve of 0.80 (95% confidence interval, 0.682-0.898) for test classification performance. The other 2 models, Small-All-Net and Elastic-All-Net, showed similar performance levels., Conclusion: A deep learning approach with 3-dimensional CNNs can distinguish IP and IP-SCC with moderate test classification performance. Although CNNs demonstrate promise to enhance the prediction of IP-SCC using MRIs, more data are needed before they can reach the predictive value already established by human MRI evaluation., (© 2022 ARS-AAOA, LLC.)