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The sinonasal tract is home to a uniquely heterogenous collection of malignant tumors. Human papillomavirus (HPV) has been detected in a number of these, but the virus' role as an oncogenic driver or coincidental finding remains unclear. We aim to highlight five sinonasal tumor types and synthesize the prevalence, etiologic role, and known clinicopathologic relevance of HPV in each.The last decade has seen an expansion of investigation into HPV's oncogenic and prognostic significance within sinonasal malignancies. The sinonasal tract poses challenges to HPV detection where p16 lacks value as an accurate surrogate. A growing body of data supports a potentially favorable clinical profile for certain sinonasal HPV-positive lesions.HPV represents a potential biologically and clinically relevant factor for some sinonasal malignancies. Definitive conclusions regarding HPV's role as a potential oncogenic agent require routine testing using validated methodologies, genomic interrogation, and large-scale prospective studies.

The lateral poststyloid space (LPSS) located at the posterolateral aspect of the styloid process. This study aims to explore the anatomical relationships in LPSS via a transoral corridor, providing reference for addressing lesions extending to this region. An endoscopic transoral approach for exposure of the LPSS was performed on 6 cadaveric specimens (12 sides). Related landmarks were explored, and transoral extirpation of tumors extended into LPSS was employed in 12 patients. The deep lobe of the parotid gland, extratemporal facial nerve, and the accompanying artery in the LPSS were sufficiently exposed via the transoral corridor in all 12 cadaveric sides. The transoral corridor provided adequate exposure for tumors extending to the LPSS, and en bloc resection was achieved in these 12 patients. No facial nerve or vascular injury occurred, and no recurrence observed in this cohort with an average follow-up of 26 months. An endoscopic transoral approach provides a direct access to the LPSS. Appreciation of the anatomical relationships within the LPSS is valuable for employing a transoral extirpation of tumors extending to this specific region.

OBJECTIVE Suprasellar meningioma resection via either the transcranial approach (TCA) or the endoscopic endonasal approach (EEA) is an area of controversy and active evaluation. Skull base surgeons increasingly consider patient-reported outcomes (PROs) when choosing an approach. No PRO measure currently exists to assess quality of life for suprasellar meningiomas. METHODS Adult patients undergoing suprasellar meningioma resection between 2013 and 2019 via EEA (n = 14) or TCA (n = 14) underwent semistructured interviews. Transcripts were coded using a grounded theory approach to identify themes as the basis for a PRO measure that includes all uniquely reported symptoms. To assess content validity, 32 patients and 15 surgeons used a Likert scale to rate the relevance of items on the resulting questionnaire and the general Patient-Reported Outcomes Measurement Information System–29 (PROMIS29). The mean scores were calculated for all items and compared for TCA versus EEA patient cohorts by using unpaired t-tests. Items on either questionnaire with mean scores ≥ 2.0 from patients were considered meaningful and were aggregated to form the novel Suprasellar Meningioma Patient-Reported Outcome Survey (SMPRO) instrument. RESULTS Qualitative analyses resulted in 55 candidate items. Relative to patients who underwent the EEA, those who underwent the TCA reported significantly worse future outlook before surgery (p = 0.01), tiredness from medications 2 weeks after surgery (p = 0.001), and word-finding and memory difficulties 3 months after surgery (p = 0.05 and < 0.001, respectively). The items that patients who received a TCA were most concerned about included medication-induced lethargy after surgery (2.9 ± 1.3), blurry vision before surgery (2.7 ± 1.5), and difficulty reading due to blurry vision before surgery (2.7 ± 2.7). Items that patients who received an EEA were most concerned about included blurry vision before surgery (3.5 ± 1.3), difficulty reading due to blurry vision before surgery (2.4 ± 1.3), and problems with smell postsurgery (2.9 ± 1.3). Although surgeons overall overestimated how concerned patients were about questionnaire items (p < 0.0005), the greatest discrepancies between patient and surgeon relevance scores were for blurry vision pre- and postoperatively (p < 0.001 and < 0.001, respectively) and problems with taste postoperatively (p < 0.001). Seventeen meningioma-specific items were considered meaningful, supplementing 8 significant PROMIS29 items to create the novel 25-item SMPRO. CONCLUSIONS The authors developed a disease- and approach-specific measure for suprasellar meningiomas to compare quality of life by operative approach. If demonstrated to be reliable and valid in future studies, this instrument may assist patients and providers in choosing a personalized surgical approach.

Background Both the endoscopic transnasal Denker’s and prelacrimal approaches provide surgical access to the pterygopalatine fossa (PPF) and infratemporal fossa (ITF). Objectives This study compares the potential maximum exposure of the PPF and ITF and quantifies the difference in surgical freedom via endoscopic Denker’s and prelacrimal approaches. Methods Six cadaveric specimens (12 sides) were dissected using a prelacrimal approach on one side and an endoscopic Denker’s approach on the contralateral side. The contents of the PPF and ITF were sequentially exposed. Surgical freedom for each corridor was subsequently calculated. Results This study confirms that both the prelacrimal and Denker’s approaches provide adequate exposure of the PPF and ITF. The maximum exposure boundaries were similar for both approaches, including the middle cranial fossa superiorly, floor of the maxillary sinus inferiorly, zygomatic arch and temporomandibular joint laterally, and post-styloid space posteriorly. However, the data revealed a statistically significant difference ( p 2) and the endoscopic Denker’s approaches (906.35 ± 38.38 mm2). Conclusion When compared with an endoscopic Denker’s approach, a prelacrimal approach seems to achieve a similar extent of exposure (ie, visualization) of the PPF and ITF. Nonetheless, the endoscopic Denker’s approach offers superior surgical freedom; thus, it is preferred for the management of complex lesions which requires increased instrument maneuverability with a 3- or 4-handed technique.

The sphenoidal spine protrudes from the roof of the infratemporal fossa (ITF). This study aims to assess the anatomic relationships among the sphenoidal spine and other structures within the ITF from the perspective of an endoscopic endonasal access (EEA), and to explore the implications of these relationships.An EEA to the ITF was completed on six cadaveric specimens (12 sides). The anatomical relationships among the sphenoidal spine and adjacent structures were explored and associated distances from each other were measured using a navigation system.The foramen spinosum is located anterosuperior to the sphenoidal spine, whereas the chorda tympani courses caudal and medial to the sphenoidal spine and the Eustachian tube and parapharyngeal internal carotid artery (pICA) are at its posterior aspect. Two virtual vertical planes, at the anterior and posterior aspects of the sphenoidal spine, respectively, correspond to the posterior trunk of VThe sphenoidal spine is a meaningful landmark for endonasal approaches to the ITF. Measurements and conceptualization of vertical planes prior and posterior to the sphenoidal spine are beneficial to better appreciate the anatomic relationships in the ITF.

PURPOSE OF REVIEW: Sinonasal malignancies are rare and understudied, often diagnosed at late stages, and may behave aggressively. This review explores investigative diagnostic, therapeutic, and scientific advances specific to sinonasal undifferentiated carcinoma (SNUC), intestinal-type adenocarcinoma (ITAC), and olfactory neuroblastoma (ONB). RECENT FINDINGS: A number of studies have recently contributed more robust knowledge of the genetic and molecular landscapes of SNUC, ITAC, and ONB. These analyses have identified SMARCB1 and IDH2 mutations in SNUC, potentially allowing for the tumor’s subdivision. Recent studies have also defined a role for induction chemotherapy in SNUC. Somatic mutations for ITAC have been identified and may be potentially targetable with FDA approved therapies. Studies defining the tumor microenvironment for ITAC and ONB have introduced the possibility of immune checkpoint inhibition for these tumor types. SUMMARY: Studies reviewed here detail promising results of the most current and novel characterization of SNUC, ITAC, and ONB genetic and molecular landscapes, which have informed ongoing therapeutic discovery. With continued multi-institutional efforts, the field of sinonasal tumor research will achieve higher disease control and improved treatment outcomes for patients afflicted with these rare cancers.

Chordoma is a rare tumor derived from notochord remnants that has a propensity to recur and metastasize despite conventional multimodal treatment. Cancer stem cells (CSC) are implicated in chordoma's resistant and recurrent behavior; thus, strategies that target CSCs are of particular interest. Using in vitro cytotoxicity models, we demonstrated that anti-programmed death ligand 1 (anti–PD-L1; N-601) and anti-EGFR (cetuximab) antibodies enhanced lysis of chordoma cells by healthy donor and chordoma patient NK cells through antibody-dependent cellular cytotoxicity (ADCC). Treatment of NK cells with an IL15 superagonist complex (N-803) increased their cytotoxicity against chordoma cells, which was further enhanced by treatment with N-601 and/or cetuximab. PD-L1–targeted chimeric antigen receptor NK cells (PD-L1 t-haNKs) were also effective against chordoma cells. CSCs were preferentially vulnerable to NK-cell killing in the presence of N-601 and N-803. Flow cytometric analysis of a chordoma CSC population showed that CSCs expressed significantly more NK-activating ligand B7-H6 and PD-L1 than non-CSCs, thus explaining a potential mechanism of selective targeting. These data suggest that chordoma may be effectively targeted by combinatorial NK cell–mediated immunotherapeutic approaches and that the efficacy of these approaches in chordoma and other CSC-driven tumor types should be investigated further in clinical studies. Significance: Combinatory immunotherapy using NK-mediated approaches demonstrates robust antitumor activity in preclinical models of chordoma and selectively targets chordoma CSCs.

The incidence of internal carotid artery (ICA) injury associated with endoscopic endonasal approaches to the pituitary is less than 1%. While parent vessel sacrifice has historically been the choice of treatment, vessel-preserving endovascular techniques have been reported. Although flow diversion offers endoluminal reconstruction, its major limitation is the delay in obtaining complete occlusion. We describe the use of a combined Pipeline embolization device (PED) with endoscopic endonasal repair using a fascia lata/muscle graft to treat an iatrogenic ICA pseudoaneurysm and report long-term radiographic follow-up. Further investigation into the utility of directed endoscopic endonasal repair of iatrogenic pseudoaneurysms initially treated with PED is necessary, especially given the need of post-PED anticoagulation and the rate of permanent neurological deficit after ICA sacrifice.

Background Caudal pneumatization of the pterygoid process may impact endonasal exposure of the lateral recess of sphenoid sinus (LRSS). Objectives This study aims to explore the implications of a pneumatized pterygoid process for an endonasal transpterygoid approach to the LRSS and to define strategies regarding the preservation or sacrifice of the vidian nerve. Methods Dissection of the LRSS (11 sides) was performed on 6 cadaveric specimens, preselected for the radiographic presence of an LRSS. In addition, the dimensions of the LRSS were measured on the deidentified CT images of 120 patients (240 sides). The sphenoid sinus was subdivided into 3 categories: Type 1 (no identifiable LRSS), Type 2 (lateral pneumatization of the greater wing above the vidian canal), and Type 3 (pneumatization of both the greater wing and the pterygoid process). Results On the cadaveric specimens, a Type 2 pneumatization often allowed access to the LRSS above the level of the vidian canal; thus, sparing the vidian neurovascular bundle. In Type 3 pneumatization, a frontal corridor through the pterygoid base could be created to reach the LRSS with preservation of the vidian nerve. Extreme Type 3 pneumatization, however, required the transposition or sacrifice of the vidian nerve to facilitate a full direct access to the superolateral LRSS. Measurements on CT images revealed that the extent of caudal pneumatization of the pterygoid process had no statistically significant correlation with the superolateral extension of the lateral recess in patients with Type 3 LRSS ( P > .05). Conclusion Pneumatization of the LRSS toward a caudal or superolateral direction may develop independent from each other. Caudal pneumatization of the pterygoid process seems to variably impact the endonasal exposure of the LRSS.

BackgroundWhile radiation and chemotherapy are primarily purposed for their cytotoxic effects, a growing body of preclinical and clinical evidence demonstrates an immunogenic potential for these standard therapies. Accordingly, we sought to characterize the immunogenic potential of radiation and cisplatin in human tumor models of HPV-associated malignancies. These studies may inform rational combination immuno-oncology (IO) strategies to be employed in the clinic on the backbone of standard of care, and in so doing exploit the immunogenic potential of standard of care to improve durable responses in HPV-associated malignancies.MethodsRetroviral transduction with HPV16 E7 established a novel HPV-associated sinonasal squamous cell carcinoma (SNSCC) cell line. Three established HPV16-positive cell lines were also studied (cervical carcinoma and head and neck squamous cell carcinoma). Following determination of sensitivities to standard therapies using MTT assays, flow cytometry was used to characterize induction of immunogenic cell stress following sublethal exposure to radiation or cisplatin, and the functional consequence of this induction was determined using impedance-based real time cell analysis cytotoxicity assays employing HPV16 E7-specific cytotoxic lymphocytes (CTLs) with or without N803 (IL-15/IL-15-Rα superagonist) or exogenous death receptor ligands. In vitro observations were translated using an in vivo xenograft NSG mouse model of human cervical carcinoma evaluating cisplatin in combination with CTL adoptive cell transfer.ResultsWe showed that subpopulations surviving clinically relevant doses of radiation or cisplatin therapy were more susceptible to CTL-mediated lysis in four of four tumor models of HPV-associated malignancies, serving as a model for HPV therapeutic vaccine or T-cell receptor adoptive cell transfer. This increased killing was further amplified by IL-15 agonism employing N803. We further characterized that radiation or cisplatin induced immunogenic cell stress in three of three cell lines, and consequently demonstrated that upregulated surface expression of Fas and TRAIL-R2 death receptors at least in part mediated enhanced CTL-mediated lysis. In vivo, cisplatin-induced immunogenic cell stress synergistically potentiated CTL-mediated tumor control in a human model of HPV-associated malignancy.ConclusionStandard of care radiation or cisplatin therapy induced immunogenic cell stress in preclinical models of HPV-associated malignancies, presenting an opportunity poised for exploitation by employing IO strategies in combination with standard of care.

BACKGROUNDHead and neck squamous cell carcinoma not associated with HPV (HPV-unrelated HNSCC) is associated with a high rate of recurrence and poor survival.METHODSWe conducted a clinical trial in 14 patients with newly diagnosed HPV-unrelated HNSCC to evaluate the safety and efficacy of neoadjuvant bintrafusp alfa, a bifunctional fusion protein that blocks programmed death ligand 1 (PD-L1) and neutralizes TGF-β.RESULTSBintrafusp alfa was well tolerated, and no treatment-associated surgical delays or complications occurred. Objective pathologic responses (PRs) were observed, and 12 of the 14 (86%) patients were alive and disease free at 1 year. Alterations in Treg infiltration and spatial distribution relative to proliferating CD8+ T cells indicated a reversal of Treg immunosuppression in the primary tumor. Detection of neoepitope-specific tumor T cell responses, but not virus-specific responses, correlated with the development of a PR. Detection of neoepitope-specific responses and PRs in tumors was not correlated with genomic features or tumor antigenicity but was associated with reduced pretreatment myeloid cell tumor infiltration. These results indicate that dual PD-L1 and TGF-β blockade can safely enhance tumor antigen-specific immunity and highlight the feasibility of multimechanism neoadjuvant immunotherapy for patients with HPV-unrelated HNSCC.CONCLUSIONOur studies provide insight into the ability of neoadjuvant immunotherapy to induce polyclonal neoadjuvant-specific T cell responses in tumors and suggest that features of the tumor microenvironment, such as myeloid cell infiltration, may be a major determinant of enhanced antitumor immunity following such treatment.TRIAL REGISTRATIONClinicalTrials.gov NCT04247282.FUNDINGThis work was funded by the Center for Cancer Research, the NCI, and the Intramural Research Program of the NIDCD, NIH. Bintrafusp alfa was provided by the health care business of Merck KGaA (Darmstadt, Germany), through a Cooperative Research and Development Agreement with the NCI. Additional funding was provided by ImmunityBio through a Cooperative Research and Development Agreement with the NIDCD.

Background Olfactory neuroblastoma (ONB) or esthesioneuroblastoma (ENB) is a rare malignancy of the nasal cavity believed to arise from the olfactory epithelium. The goal of this study was to systematically review the genomics, epigenetics, and cytogenetics of ONB and to understand the potential clinical implications of these studies. Methods A systematic literature review was performed for articles published before May 2020 using Cochrane, Embase, Pubmed, and Scopus databases. Inclusion criteria included genomics, cytogenetics, and epigenetics studies on ONB. Exclusion criteria included studies not in English or systematic reviews. Articles and abstracts were reviewed by two independent reviewers to reduce bias during article selection and synthesis of results. Of the 36 studies included in this review, 24 were research articles and 12 were abstracts. Results Although recurrent mutations among ONB tumors are uncommon, alterations in TP53, DMD, PIK3CA, NF1, CDKN2A, CDKN2C, CTNNB1, EGFR, APC, cKIT, cMET, PDGFRA, CDH1, FH, SMAD4, FGFR3 and IDH2 genes have been reported in several recent studies. In addition, cytogenetic studies revealed that the landscape of chromosomal aberrations varies widely amongst ONB tumors. Conclusions The rare character of ONB has limited the sample size available for cytogenetic, genomic, and epigenetic studies and contributes to the limitations of this systematic review. Comprehensive genomic and epigenomic studies with larger cohorts are warranted to validate the initial reports summarized in this review and to identify potential therapeutic targets for ONB.

Objectives Sinonasal mucosal melanoma (SNMM) is an extremely rare and challenging sinonasal malignancy with a poor prognosis. Standard treatment involves complete surgical resection, but the role of adjuvant therapy remains unclear. Crucially, our understanding of its clinical presentation, course, and optimal treatment remains limited, and few advancements in improving its management have been made in the recent past. Methods We conducted an international multicenter retrospective analysis of 505 SNMM cases from 11 institutions across the United States, United Kingdom, Ireland, and continental Europe. Data on clinical presentation, diagnosis, treatment, and clinical outcomes were assessed. Results One-, three-, and five-year recurrence-free and overall survival were 61.4, 30.6, and 22.0%, and 77.6, 49.2, and 38.3%, respectively. Compared with disease confined to the nasal cavity, sinus involvement confers significantly worse survival; based on this, further stratifying the T3 stage was highly prognostic (p Conclusions We present findings from the largest cohort of SNMM reported to date. We demonstrate the potential utility of further stratifying the T3 stage by sinus involvement and present promising data on the benefit of immune checkpoint inhibitors for recurrent, persistent, or metastatic disease with implications for future clinical trials in this field.

A trans-lateral oropharyngeal wall approach (TLOWA) to the petrous apex has not been previously defined. This study aims to assess the feasibility of a TLOWA for surgical access to the petrous apex and the petroclival region.An endoscopic TLOWA for exposure of the petrous apex and petroclival region was performed on five cadaveric specimens (10 sides). Associated anatomical landmarks were defined, and the strategies for maximal exposure of the internal carotid artery (ICA) were explored.Via a TLOWA, the parapharyngeal ICA was widely exposed in all 10 sides. Following transection of the Eustachian tube, the inferior petrous apex and petroclival region could be sufficiently exposed. After drilling the anteroinferior bony canal, the horizontal petrous ICA, foramen lacerum, and the paraclival ICA could be adequately revealed.The TLOWA may provide an alternative corridor for access to the petrous apex and the petroclival region. The parapharyngeal, petrous, lower paraclival ICAs, and the foramen lacerum could be adequately exposed via the TLOWA.

Introduction: Extirpation of multiple head and neck paragangliomas carries challenge due to close anatomic relationships with critical neurovascular bundles. Objectives: This study aims to assess whether the application of 3-D models can assist with surgical planning and treatment of these paragangliomas, decrease surgically related morbidity and mortality. Methods: Fourteen patients undergoing surgical resection of multiple head and neck paragangliomas were enrolled in this study. A preoperative 3-D model was created based on radiologic data, and relevant critical anatomic relationships were preoperatively assessed and intraoperatively validated. Results: All 14 patients presented with multiple head and neck paragangliomas, including bilateral carotid body tumors (CBT, n = 9), concurrent CBT with glomus jugulare tumors (GJT, n = 4), and multiple vagal paragangliomas (n = 1). Ten patients underwent genomic analysis and all harbored succinate dehydrogenase complex subunit D (SDHD) mutations. Under guidance of the 3-D model, the internal carotid artery (ICA) was circumferentially encased by tumor on 5 of the operated sides, in 4 (80%) of which the tumor was successfully dissected out from the ICA, whereas ICA reconstruction was required on one side (20%). Following removal of CBT, anterior rerouting of the facial nerve was avoided in 3 (75%) of 4 patients during the extirpation of GJT with assistance of a 3-D model. Two patients developed permanent postoperative vocal cord paralysis. There was no vessel rupture or mortality in this study cohort. Conclusion: The 3-D model is beneficial for establishment of a preoperative strategy, as well as planning and guiding the intraoperative procedure for resection of multiple head and neck paragangliomas.

Cities across the globe are faced with (re)developing cruise infrastructure because of the increase in the number, size and capacity of cruise ships. Infrastructure development involves stakeholder networks which embrace competing interests, potentially leading to network fragmentation and associated risks. Despite prior studies identifying the risks that can arise from network fragmentation in infrastructure development, there is little research considering this issue explicitly in the context of cruise infrastructure development. This paper explores the extent to which network fragmentation can lead to risks impacting the development of cruise infrastructure. Twenty-three semi-structured interviews were conducted with key stakeholders in Auckland, New Zealand. Results demonstrate that network fragmentation was evident, leading to critical risks. Fragmentation was driven by political instability, competing interests, inadequate governance, and a lack of: a) effective leadership, b) a coordinated national strategy or vision, c) transparency, d) trust, and e) inclusiveness, particularly in the planning phase.

Background: Olfactory neuroblastoma (ONB), also known as esthesioneuroblastoma, is a rare malignancy of the nasal cavity and anterior skull base. Multispectral immunofluorescence (mxIF), allows for comprehensive evaluation of tumor immune cell spatial relationships and thorough characterization of the tumor immune microenvironment (TIME). The objective of this study was to comprehensively define the ONB myeloid cell TIME with mxIF. Methods: A tissue microarray including 47 clinically annotated human ONB samples was obtained, in addition to IRB approval, from our tertiary care hospital. A myeloid specific panel was validated in ONB tissue as well as controls. The panel stained for CD15, CD68, CD11b, CD14, HLA-DR, synaptophysin, and DAPI. Phenotypes of interest included CD11b+/CD15+/CD14−/HLA-DRlow/− polymorphonuclear leukocytes (PMNs), CD11b+/CD14+/CD15−/HLA-DR low/−monocytes, and CD68+ Pan Macrophages. HALO image analysis v3.4 was used to objectively quantify immune cell spatial relationships. A retrospective chart review was performed from these clinically annotated specimens with collection of patient demographics, stage, Hyams grade, dural infiltration status, and outcomes. Results: Three samples were excluded based on too little available tissue for meaningful analysis. Of the remaining 44, 38 were primary and 6 were recurrent tumors. PMNs, monocytes, and macrophages are present in the TIME of ONB at 22 cells per mm2, 2.0 cells per mm2, and 34 cells per mm2 respectively. Increased PMN and macrophage cell densities were noted in the stroma when compared to the tumor parenchyma (28 cells per mm2 vs 14 cells per mm2, p Conclusion: This study is the first to comprehensively define the ONB myeloid TIME using mxIF. Our study demonstrates the ONB TIME contains abundant myeloid populations. As these cells have been shown to be immunosuppressive, thereby fostering tumor cell escape and host evasion, in other human malignancies we posit they play a similar role in ONB. The functional study of myeloid populations in ONB, and whether they represent targets for therapeutic intervention, is warranted. Citation Format: Riley Larkin, Diana Lopez, Yvette Robbins, Wiem Lassoued, Gary Gallia, Clint T. Allen, Nyall R. London. Multispectral immunofluorescence analysis of the olfactory neuroblastoma tumor immune microenvironment reveals macrophage and polymorphonuclear leukocyte stroma localization and tumor parenchyma exclusion. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 4706.

Defects resulting from open resection of anterior skull base neoplasms are difficult to reconstruct. Our objective was to review the literature and describe an evidence-based algorithm that can guide surgeons reconstructing anterior skull base defects.A research librarian designed database search strategies. Two investigators independently reviewed the resulting abstracts and full text articles. Studies on reconstruction after open anterior skull base resection were included. Studies of lateral and posterior skull base reconstruction, endoscopic endonasal surgery, traumatic and congenital reconstruction were excluded. Based on the review, a reconstructive algorithm was proposed.The search strategy identified 603 unique abstracts. 53 articles were included. Adjacent subsites resected, defect size, radiotherapy history, and contraindications to free tissue transfer were identified as key factors influencing decision making and were used to develop the algorithm. Discussion of the reconstructive ladder as it applies to skull base reconstruction and consideration of patient specific factors are reviewed. Patients with a prior history of radiotherapy or with simultaneous resection of multiple anatomic subsites adjacent to the anterior skull base will likely benefit from free tissue transfer.Reconstruction of anterior skull base defects requires knowledge of the available reconstructive techniques and consideration of defect-specific and patient-specific factors.

Objective Structural anomalies of the jugular foramen (JF) and adjacent structures may contribute to development of pulsatile tinnitus (PT). The goal of this study was to assess anatomical variants in the ipsilateral JF region in patients with PT and to explore possible predisposing factors for PT. Methods One hundred ninety-five patients with PT who underwent CT angiography and venography of the temporal bone were retrospectively analyzed. Anatomic variants including dominance of the ipsilateral JF, bony deficiency of the sigmoid sinus and internal carotid artery canal, high riding or dehiscent jugular bulb, dehiscence of the superior semicircular canal, tumors in the JF region, or cerebellopontine angle were assessed. Results Of 195 patients with PT, the prevalence of a dominant JF on the ipsilateral side of patients with PT was 67.2%. Furthermore, the dominant JF demonstrated a significant correlation with the presence of ipsilateral PT (p Conclusion Structural abnormalities of the JF and adjacent structures may predispose to the development of PT. Knowledge of these anatomical variants in the JF region may help establish a clinical strategy for addressing PT.

Background: ARF nucleotide-binding site opener (ARNO) is a guanine nucleotide-exchange factor for ADP-ribosylation factor proteins. ARF nucleotide-binding site opener also binds MyD88, and small-molecule inhibition of ARNO reduces inflammation in animal models of inflammatory arthritis and acute inflammation. However, whether genetic deletion of Arno in mice reduces pathologic inflammation has not yet been reported. Furthermore, its role in the nasal cavity has yet to be investigated. Objective: To generate Arno knockout mice and to determine whether genetic loss of ARNO reduces eosinophilic inflammation in the ovalbumin (OVA) murine model of rhinitis. Methods: Arno knockout mice were generated and wild type and knockout littermates were subjected to the OVA-induced mouse model of rhinosinutitis. Eosinophilic inflammation was assessed through immunofluorescent quantification of EMBP+ eosinophils in the septal mucosa and cytokine expression was assessed by quantitative polymerase chain reaction. Results: Arno knockout mice are viable and fertile without any noted deficits. Arno wild type and knockout mice subjected to the OVA-induced model of rhinitis demonstrated an average of 314.5 and 153.8 EMBP+ cells per mm2 septal tissue, respectively ( P < .05). Goblet cells per mm of basal lamina were assessed via Alcian blue and there was no statistically significant difference between Arno wild type and knockout mice. Ovalbumin-induced expression of interleukin-5 (IL-5) was significantly reduced in Arno knockout mice ( P < .05). There was no statistically significant reduction in IL-4, IL-13, or eotaxin-1 expression. Conclusions: These data demonstrate that deletion of Arno reduces eosinophilic inflammation and IL-5 expression in an OVA-induced model of rhinitis.

Performing a nasopharyngectomy via a transoral approach has been reported; however, defining landmarks to facilitate this approach has not been addressed. This study aims to explore anatomical landmarks to aid in performing a nasopharyngectomy via the transoral corridor.An endoscopic transoral nasopharyngectomy was performed on six cadaveric specimens (12 sides). Related anatomical landmarks were defined, and the strategy to preserve the parapharyngeal internal carotid artery (pICA) was explored.An endoscopic transoral nasopharyngectomy was successfully achieved in all 12 sides. Utilizing the pterygoid hamulus as a landmark, the cartilaginous ET and attachments could be adequately exposed. Identification of the pICA is a prerequisite prior to Eustachian tube (ET) transection. The sphenoidal spine and the petrotympanic fissure could be sufficiently revealed in all 12 sides, which aided in transection of the cartilaginous ET without pICA injury. The ET and the prevertebral contents could be adequately removed via the transoral corridor.The pterygoid hamulus, sphenoidal spine and petrotympanic fissure serve as reliable landmarks for performing a transoral nasopharyngectomy. Identification of the pICA is a prerequisite prior to transection of the ET to avoid pICA injury.

The styloid process constitutes the posterolateral boundary for an endonasal exposure of the infratemporal fossa. This study aims to explore the feasibility of a far-lateral extension to the lateral poststyloid space via an endonasal corridor. An endonasal dissection was performed on six cadaveric specimens (12 sides). Following an endoscopic endonasal access to the parapharyngeal space, the styloid process and the tympanic portion of the temporal bone were removed to reveal the jugular bulb and the extratemporal facial nerve. Distances from the anterior nasal spine to the relevant landmarks were measured using a surgical navigation device. Through an endonasal corridor, only the anteroinferior aspect of the jugular bulb was exposed. Conversely, the extratemporal facial nerve could be sufficiently exposed, and the deep temporal nerve could be transposed to the stylomastoid foramen. The average horizontal distances from the nasal spine to the posterior tract of V

Endoscopic access to the petrous apex and petroclival region often requires sacrificing the Eustachian tube (ET). This study aimed to compare the maximum exposure of the petrous apex and petroclival region via an endonasal corridor when sparing or resecting the ET and its torus. Six cadaveric specimens (12 sides) were dissected through an endonasal transpterygoid approach. Endonasal exposure of the petroclival region was completed using techniques that included the preservation of the ET (group 1), resection of the torus tubarius (group 2), and resection of the ET (group 3) were sequentially performed on each side. The working distances from the anterior genu of the petrous internal carotid artery (ICA) to the inferior boundaries of each corridor were measured and compared. In group 1, the medial petrous apex and petroclival sulcus could be exposed with a working distance of 4.08 ± 0.67 mm. In group 2, the fossa of Rosenmüller, inferior petrous apex, and hypoglossal canal could be exposed, with a significantly increased working distance of 18.33 ± 0.89 mm (P = .001). In group 3, the exposure and ICA control was superior and offered a working distance of 20.67 ± 0.78 mm. No statistically significant difference derived from comparing groups 2 and 3 (P = .875). Resection of the torus tubarius can increase exposure of the petrous apex and petroclival region. It provides an alternative to resecting the ET, which might be beneficial for maintenance of middle ear function. ET resection, however, seems superior when ICA control is required.

This study aimed to ascertain the maximal exposure of the superior orbital fissure (SOF) afforded by combining endonasal and transorbital endoscopic approaches. Six cadaveric specimens (12 sides) were dissected using endonasal and transorbital endoscopic approaches to access the SOF. The order of the approaches was alternated in each specimen (eg, starting with an endonasal approach in one side followed by a transorbital exposure and reversing the order on the contralateral side). Maximal exposure of the SOF and its contents for individual and combined approaches were explored. The endonasal corridor provided adequate access to the inferomedial 1/3 of the SOF and including the proximal segments of cranial nerves (CN) III, V1 and VI. A transorbital approach was superior accessing the superolateral 2/3's of the SOF, including the superior ophthalmic vein, lacrimal nerve, and distal segment of the CN VI at the lateral aspect; the nasociliary nerve and divisions of CN III centrally; and the frontal nerve and CN IV at the dorsal aspect of levator palpebrae superioris. This study suggests that a combined endonasal and transorbital exposure of the SOF may be advantageous to address lesions in this challenging region.

Background Recent reports have investigated the nascent role of induction chemotherapy for sinonasal undifferentiated carcinoma (SNUC). The goal of this study was to ascertain trends in treatment pattern changes for SNUC at a single institution and design a treatment algorithm utilized at our institution. Methods Retrospective chart analysis of 21 cases of SNUC from 2010 to 2018. Results Of 21 patients in this cohort, 18 (85.7%) presented with T4 disease, 7 (33.3%) presented with nodal disease, and 3 (14.3%) presented with distant metastasis. Since 2016, patients have been managed by induction chemotherapy followed by concurrent chemoradiation. To this point, patients treated with TPF induction chemotherapy followed by concurrent chemoradiation show no evidence of disease; however, the average follow up time is 16.8 months. Conclusions The multimodality treatment for SNUC continues to evolve, as highlighted by this study, toward increased use of induction chemotherapy followed by chemoradiotherapy.

BACKGROUND Although treatment with checkpoint blockade is now accepted as standard of care for cutaneous melanoma, few studies have investigated its role in sinonasal melanoma (SNM). We aimed to evaluate whether immunotherapy was associated with improved survival in SNM and to compare the effect of immunotherapy in metastatic sinonasal and cutaneous melanoma. METHODS This was a cohort study of patients included in the United States National Cancer Database who had been diagnosed with sinonasal or cutaneous melanoma between 2012 and 2015 and had complete information regarding immunotherapy status. The primary outcome was overall survival. The influence of immunotherapy on overall survival was compared by Kaplan-Meier and Cox proportional hazards models. Propensity score matched analyses between SNM patients who received immunotherapy and those who did not were based on clinicopathological covariates associated with survival in univariate Cox models. RESULTS The analytic cohort consisted of 704 patients with SNM, 94 of whom were treated with immunotherapy and 152,896 patients with cutaneous melanoma, 8055 of whom were treated with immunotherapy. Immunotherapy was not associated with survival in the propensity-score matched cohort (n = 195; hazard ratio [HR] = 1.0; 95% confidence interval [CI], 0.7 to 1.5; p = 0.88) or in adjusted Cox proportional hazards model (n = 549; HR = 1.0; 95% CI, 0.74 to 1.4; p = 0.88). Regimens including immunotherapy were associated with improved overall survival in metastatic cutaneous melanoma (HR = 0.57; 95% CI, 0.49 to 0.66; p < 0.0001), but not metastatic SNM (HR = 1.1; 95% CI, 0.67 to 1.7; p = 0.75). CONCLUSION Compared to current standard of care therapy, inclusion of immunotherapy as first-line therapy was not associated with improved survival in SNM.

Background Endoscopic transethmoidal and prelacrimal approaches can access the medial intraconal space (MIS). Objective This study aimed to compare advantages and drawbacks of these two approaches, and to explore their appropriate indications for management of lesions at various locations within the MIS. Methods Six injected cadaveric specimens were dissected using an endonasal approach performing a transethmoidal approach on one side and a prelacrimal approach on the contralateral side. The MIS was divided into three Zones: Zone 1 was defined as the area above the superior border of the medial rectus muscle (MRM), Zone 2 as the area between the MRM and the optic nerve, and Zone 3 as the area below the inferior border of MRM. The exposure provided by these two approaches to various Zones within the MIS was assessed and compared. Results The average height of Zone 1 to 3 was 10.35 ± 0.45 mm, 11.07 ± 0.59 mm, and 6.53 ± 0.59 mm, respectively. Both approaches provided adequate exposure of Zone 2 and 3; however, the prelacrimal approach provided direct exposure of the posterosuperior aspect of Zone 2 without retraction of MRM. Retraction of MRM was unavoidable using a transethmoidal approach to enhance further exposure. Access to Zone 1 was adequately achieved through the corridor between superior oblique muscle and MRM via a transethmoidal corridor. Conclusion Conceptualizing the MIS into the three aforementioned Zones seems beneficial to select the optimal approach for lesions restricted to each specific Zone. Both the transethmoidal and prelacrimal approaches provide adequate exposure for select lesions in the MIS.

Background Delayed postoperative cerebrospinal fluid (CSF) leaks are uncommon and largely unstudied complications. In this study we aim to identify their etiology and understand the efficacy of various reconstruction strategies. Methods A retrospective chart analysis of 1017 endonasal skull base surgeries performed by a single neurosurgeon was completed identifying delayed CSF leaks (occurring >1 week after surgery). Results Seventeen cases of early (1-2 weeks after surgery) or delayed (>2 weeks after surgery) postoperative CSF leak were identified. The most common reconstruction during the initial surgery consisted of an inlay or gasket seal collagen matrix (82.4% of patients) with an onlay pedicled flap (76.5% of patients). Presenting symptoms of delayed CSF leak included rhinorrhea (82.4%), headache (41.2%), and meningitis (23.5%). The most common causes included flap dehiscence (17.6%); provoking events such as emesis, sneezing, or fall (17.6%); flap necrosis (11.8%); flap displacement (11.8%); and inadequate apposition of the flap, that is, folded flap (11.8%). Reconstructive techniques of the delayed CSF leak included fortification of the initial reconstruction with free fat grafts (29.4% of patients), combined collagen matrix with a fat graft (23.5% of patients), repositioning of the previous flap (11.8% of patients), and repair with a new flap (11.8% of patients). CSF diversion (spinal/ventricular drain or shunt) was used in 17.6% of patients. Conclusion This study identifies the most common etiologic factors leading to a delayed CSF leak and its initial symptoms. Furthermore, it serves as the foundation for a reconstructive algorithm based on reinforcement of the initial repair with free abdominal fat graft with or without collagen matrix.

BackgroundThe anterolateral triangle enclosed by the foramen rotundum and foramen ovale constitutes part of the floor of the middle cranial fossa (MCF).ObjectiveTo assess the feasibility of a transnasal prelacrimal approach for accessing the floor of MCF via an anterolateral triangle corridor and to determine the extent of maximal exposure while safeguarding neurovascular structures.MethodsA transnasal prelacrimal approach was performed in 5 cadaveric specimens (10 sides). Following the identification of foramen rotundum and foramen ovale, the bony ridge between 2 was drilled to expose the MCF. The temporal lobe dura was then elevated laterally, and the distances from foramen ovale to the respective borders of the area of the MCF window were measured using a surgical navigation device.ResultsThe MCF was exposed with a 0° scope in all specimens also exposing significant landmarks including the middle meningeal artery, greater superficial petrosal nerve, superior petrous sinus, and arcuate eminence. Average distances from foramen ovale to the anterior, posterior, and lateral exposed borders were 22.86 ± 1.87 mm, 27.24 ± 0.94 mm, and 24.23 ± 1.61 mm, respectively. The average area of exposed MCF window was 554.12 ± 60.22 mm2. Preservation of vidian nerve, greater palatine nerve, lateral nasal wall, and nasolacrimal duct was possible in all 10 sides.ConclusionIt is feasible to access the floor of MCF via an endoscopic transnasal prelacrimal approach with seemingly low risk.