Edward El Rassi

Improvements in sleep-related symptoms after endoscopic sinus surgery in patients with chronic rhinosinusitis

Sleep impairment is highly prevalent in patients with chronic rhinosinusitis (CRS). Although endoscopic sinus surgery (ESS) has been shown to improve overall patient‐reported sleep quality, the postoperative impact on individual sleep symptoms remains unclear.

Sensitivity analysis and diagnostic accuracy of the Brief Smell Identification Test in patients with chronic rhinosinusitis

The Brief Smell Identification Test (BSIT) is an abbreviated version of the Smell Identification Test (SIT) used to assess olfactory function. Although the BSIT can be efficiently administered in under 5 minutes, the accuracy of the BSIT in relation to the SIT in patients with chronic rhinosinusitis (CRS) is unknown.

Cell Adhesion Molecule CD166/ALCAM Functions Within the Crypt to Orchestrate Murine Intestinal Stem Cell Homeostasis

Background & Aims Intestinal epithelial homeostasis is maintained by active-cycling and slow-cycling stem cells confined within an instructive crypt-based niche. Exquisite regulating of these stem cell populations along the proliferation-to-differentiation axis maintains a homeostatic balance to prevent hyperproliferation and cancer. Although recent studies focus on how secreted ligands from mesenchymal and epithelial populations regulate intestinal stem cells (ISCs), it remains unclear what role cell adhesion plays in shaping the regulatory niche. Previously we have shown that the cell adhesion molecule and cancer stem cell marker, CD166/ALCAM (activated leukocyte cell adhesion molecule), is highly expressed by both active-cycling Lgr5+ ISCs and adjacent Paneth cells within the crypt base, supporting the hypothesis that CD166 functions to mediate ISC maintenance and signal coordination. Methods Here we tested this hypothesis by analyzing a CD166–/– mouse combined with immunohistochemical, flow cytometry, gene expression, and enteroid culture. Results We found that animals lacking CD166 expression harbored fewer active-cycling Lgr5+ ISCs. Homeostasis was maintained by expansion of the transit-amplifying compartment and not by slow-cycling Bmi1+ ISC stimulation. Loss of active-cycling ISCs was coupled with deregulated Paneth cell homeostasis, manifested as increased numbers of immature Paneth progenitors due to decreased terminal differentiation, linked to defective Wnt signaling. CD166–/– Paneth cells expressed reduced Wnt3 ligand expression and depleted nuclear β-catenin. Conclusions These data support a function for CD166 as an important cell adhesion molecule that shapes the signaling microenvironment by mediating ISC–niche cell interactions. Furthermore, loss of CD166 expression results in decreased ISC and Paneth cell homeostasis and an altered Wnt microenvironment.

Overlapping Morphologic and Immunohistochemical Features of Hashimoto Thyroiditis and IgG4-Related Thyroid Disease

Immunoglobulin G4-related disease (IgG4-RD) is an emerging clinicopathologic entity characterized by both IgG4+ plasma cell infiltration and fibrosis in one or more organs, prototypically pancreas or salivary/lacrimal glands. IgG4-RD in the thyroid (IgG4-RTD) is an area of active study, and the relationship between IgG4-RTD and Hashimoto thyroiditis is not fully delineated due to their overlapping histologic features. Retrospective review was performed of all thyroidectomy cases demonstrating lymphocytic inflammation at a single institution over a 4-year period. Approximately half (23/38) of patients had a clinical diagnosis of Hashimoto thyroiditis (HT). Nine of the 38 patients had increased absolute and relative numbers of IgG4+ plasma cells. Patients with a clinical diagnosis of HT had increased lymphoplasmacytic inflammation, but the relative proportion of IgG4+ plasma cells was not increased compared to patients without HT. There was no correlation between IgG4 levels and the amount of fibrosis in patients with or without HT. Patients identified as having the fibrosing variant of HT were not more likely to have increased levels of IgG4+ plasma cells than those without. There is significant morphologic and immunohistochemical overlap between HT and IgG4-RTD. Future studies to identify specific characteristics of IgG4-RTD involving the thyroid are necessary to accurately define this entity.

Improving outcomes in veterans with oropharyngeal squamous cell carcinoma through implementation of a multidisciplinary clinic

Treatment of head and neck cancer is complex, and a multidisciplinary clinic may improve the coordination of care. The value of a head and neck multidisciplinary clinic has not yet been established in oropharyngeal squamous cell carcinoma (SCC).

Lymphoma of the nasal cavity and paranasal sinuses: A case series.

Background Lymphomas of the sinonasal tract are a rare and heterogeneous subset of solid sinonasal neoplasms. Objective To characterize, in this case series, presenting symptoms, treatment modalities, and outcomes for patients with sinonasal lymphoma within a single institution. Methods Retrospective patient data were collected from an academic, oncologic center and entered into a repository designed to capture outcomes for sinonasal malignancies. Patient demographics, presenting symptoms, imaging findings, treatment modalities, and health status were retrospectively extrapolated and evaluated by using Kaplan-Meier estimations for survival probability. Results Patients with sinonasal lymphoma with a mean follow-up of 50 months were identified (n = 18). Histologic diagnosis included the following: diffuse large B-cell lymphoma (n = 9), natural killer/T-cell lymphoma (n = 5), follicular lymphoma (n = 1), T-cell lymphoma (n = 1), and lymphoma-not otherwise specified (n = 2). The most frequent presenting symptoms were nasal obstruction (78%), facial pain (72%), facial swelling (50%), and nasal discharge (44%). Treatment before lymphoma diagnosis included antibiotics (83%), oral steroids (22%), decongestants (22%), and topical steroids (11%). Treatment regimens after diagnosis included both chemotherapy (94%) and chemoradiotherapy (56%). Survival rates by lymphoma subtype were 56% for B-cell lymphoma and 40% for natural killer/T-cell lymphoma. Overall, 2- and 5-year survival rates were 67% and 50%, respectively. The combination of chemotherapy and radiation resulted in significantly higher survival rates (p ≤ 0.001) than chemotherapy alone. Conclusion Sinonasal lymphomas are characterized by meager survival rates, which differ by histopathologic subtype. The diagnosis of sinonasal lymphoma is challenging because symptoms frequently parallel those of chronic rhinosinusitis. Increased awareness of these rare malignancies may improve detection and more timely treatment. Clinical trial registration NCT01332136.

Propranolol-responsive cranial nerve palsies in a patient with PHACES syndrome

PHACES syndrome is a neurocutaneous disorder characterized by the presence of segmental hemangiomas with associated anomalies of the posterior fossa, cerebral vasculature, cardiovascular system, eyes, and ventral or midline structures. We present the first case of propranolol-responsive congenital trigeminal and facial nerve palsies secondary to an intracranial hemangioma in a patient with PHACES syndrome.

Technical Refinements and Outcomes of the Modified Anterior Septal Transplant

Importance Severe anterior septal deviation and resultant nasal obstruction represent a difficult surgical task to correct. The goal of surgery is to straighten the anterior dorsal and caudal struts, while maintaining nasal tip and midvault support. This study presents a novel extracorporeal septoplasty technique to straighten the crooked anterior septum. Objective To describe the novel anterior septal transplant technique, which consists of complete resection of the caudal septum and reconstruction with extended spreader grafts and a columellar strut, without a separate caudal septal replacement graft. Design, Setting, and Participants This study was a retrospective case series at a tertiary academic referral center. Participants were sequential adult patients undergoing anterior septal transplant from January 1, 2008, to December 31, 2015. Main Outcomes and Measures Patient-reported nasal obstruction using Nasal Obstruction Symptom Evaluation (NOSE) scores and objective photographic analysis. Nasal tip deviation, projection, and rotation were measured. Preoperative and postoperative outcomes were compared. Complications are reported. Results Seventy-one patients (mean age, 46 years [age range, 16-72 years]; 48 [67.6%] female and 23 [32.4%] male) were included in the case series. Postoperative NOSE scores (mean [SD], 24.00 [24.58]) were significantly better than preoperative NOSE scores (mean [SD], 72.25 [14.55]) (P < .001). A separate cohort of 32 patients (mean age, 42 years [age range, 13-72 years]; 23 [71.9%] female and 9 [28.1%] male) had photographs available for analysis. In the frontal view, nasal deviation improved from a mean (SD) of 2.9 (2.0) degrees before surgery to a mean (SD) of 1.4 (1.7) degrees after surgery (P = .004). In the base view, the deviation was corrected from a mean (SD) of 4.9 (2.8) degrees to a mean (SD) of 1.7 (1.2) degrees (P < .001). Tip rotation and projection were unchanged after surgery. Four patients had mild dorsal irregularities after surgery. Conclusions and Relevance Anterior septal transplant by the described technique is a safe and effective treatment option for severe anterior septal deviation. Level of Evidence 4.

Practice patterns in the management of post-tonsillectomy hemorrhage: An American Society of Pediatric Otolaryngology survey

OBJECTIVES To evaluate practice patterns amongst pediatric otolaryngologists in the management of post-tonsillectomy hemorrhage. METHODS A cross-sectional survey of the American Society of Pediatric Otolaryngology membership was administered electronically. The survey contained questions related to practice type, availability of resident and fellow call coverage, and management of different scenarios of post-tonsillectomy hemorrhage. Anonymous responses were collected and tabulated. RESULTS The response rate was 157/443 (35%). For patients presenting with a convincing history of post-tonsillectomy hemorrhage but no clot or bleeding on exam, the most common management was overnight observation (55%) or discharge home with close follow-up (29%). In patients presenting with tonsillar clot but no active bleeding, the most common management was operating room for control (50%), followed by observation (25%) and bedside topical treatment (13%). In the same scenario with a cooperative teenager, bedside topical treatment was most common (45%), followed by operating room for control (27%) and observation (16%). In patients presenting with active tonsillar bleeding, operating room for control was most common (83%) while few (6%) attempted bedside treatment. If the patient was a cooperative teenager, 38% attempted bedside treatment while 52% would still go to the operating room. CONCLUSIONS There is substantial variation in the management of post-tonsillectomy hemorrhage amongst the pediatric otolaryngologists. Further studies to determine outcomes associated with differing treatment strategies would be useful in establishing practice recommendations.

Abstract 1631: FGF2 activation of FGFR1 in head and neck squamous cell carcinoma is associated with more invasive disease and can be attenuated by FGFR inhibition

Introduction. Head and neck squamous cell carcinomas (HNSCCs) account for nearly 600,000 deaths worldwide annually and have limited treatment options. Approximately 20% of HNSCCs harbor amplifications of fibroblast growth factor receptor 1 (FGFR1) on chromosome 8p, however FGFR1 amplification by itself does not predict clinical response to FGFR inhibitors. We hypothesized that FGF2, or basic FGF, ligand expression is a better marker of FGFR activation and predictor of response to FGFR inhibitors. Results. A tissue micro array (TMA) of HNSCC patient biopsies was stained and quantitated for FGF2 expression by Aperio ImageScope software. FGF2 was significantly increased in recurrent tissue samples (p = 0.04). We examined a number of immortalized HNSCC cell lines and found that overexpression of both FGF2 and FGFR1 predicted response to the selective FGFR inhibitor PD173074. FGFR inhibition did not cause apoptosis, but rather induced a G0/G1 arrest and growth inhibition. FGFR inhibition also induced a change in cell morphology, with a significant increase in cell size and adherence. The expression of epithelial-to‐mesenchymal transition (EMT) proteins was examined and FGF2-FGFR1 activation was associated with a more mesenchymal phenotype. Accordingly, FGFR inhibition reversed invasiveness as measured using the Incucyte WoundMaker scratch assay, suggesting that HNSCCs with FGF2-FGFR1 activation have more metastatic potential. Invasiveness of these cells in vivo was confirmed using orthotopic injection into the buccal pad of NSG mice. Once primary tumors reached 0.8 cm in size, mice were sacrificed and buccal mucosa, lung, liver, and neck tissue were examined post-mortem. All of the injected animals developed local invasion, and distant metastases in the lungs. 5/7 mice also had metastases in the liver and this model is being used to test the ability of FGFR inhibition to prevent metastasis. The mechanism of autocrine FGF2-FGFR1 activation was further explored and FGF2 was found to be secreted in association with extracellular vesicles (ECVs). Interestingly, inhibition of FGFR reduced secretion of ECVs and FGF2, providing a novel approach to target autocrine and paracrine FGFR1 activation within the tumor. We further tested a number of small molecule inhibitors in combination with PD173074 to look for synergistic combinations of kinase inhibitors and found significant synergy between EGFR and FGFR inhibitors suggesting this combination may be most effective in patients with HNSCC. Conclusions. Increased FGF2 in HNSCC patient samples is correlated with recurrent disease. FGF2-FGFR1 activation increases invasiveness through activation of EMT genes both in vitro, and in an orthotopic model. Inhibition of FGF2-FGFR1 reversed the invasive phenotype in vitro and may be an effective therapeutic strategy to reduce metastases in HNSCC patients. Citation Format: Isabel A. English, Jacqueline Martinez, Edward El Rassi, Mark Schmidt, Ellen Langer, Sophia Bornstein, John Gleysteen, Melissa Wong, Brian Druker, Elie Traer. FGF2 activation of FGFR1 in head and neck squamous cell carcinoma is associated with more invasive disease and can be attenuated by FGFR inhibition. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 1631.