The Role of Denosumab Treatment in Recurrent Giant Cell Bone Tumor of the Orbit.

Giant cell tumor of the bone (GCTB) is a rare primary bone neoplasm, representing about 5% of all primary bone tumors. Most GCTBs are found in the epiphysis of long bones, with only 2% of GCTBs involving the skull. In recent years, the receptor activator of nuclear factor Kappa ligand monoclonal antibody denosumab has been demonstrated as a promising therapeutic option for GCTB; however, this is an evolving field. We present a case of a 57-year-old female with a rare GCTB in the right orbit and sinuses, originally thought to be an aneurysmal bone cyst. Her symptoms included proptosis, intermittent blurry vision, sinus congestion, and frontal headaches. After excision, the tumor recurred within 18 months. Upon repeat excision, a diagnosis of GCTB was made. The patient started denosumab therapy and had no tumor growth over the ensuing 2 years, with stability of symptoms and clinical signs on follow-up.

Intraosseous Cavernous Hemangioma of the Middle Turbinate: A Case Report.

BACKGROUND: We report a case of an intraosseous cavernous hemangioma originating from the middle turbinate that expanded into the anterior skull base, without traversing the cribriform plate. METHODS: The mass was found incidentally after a computed tomography head was ordered for unrelated reasons. On questioning, the patient denied any nasal symptoms. Magnetic resonance imaging showed an enhancing mass and the radiological imaging supported a broad differential. RESULTS: The lesion was removed by endoscopic image-guided surgery, and the pathology was that of a benign intraosseous cavernous hemangioma. There was no residual hemangioma on postoperative imaging and the nasal mucosa healed well. This is the first report of an intraosseous cavernous hemangioma of the middle turbinate showing superior expansion to the anterior skull base. CONCLUSION: This case demonstrates the extent to which cavernous hemangiomas may expand into surrounding tissues. While these lesions are uncommon, they can be considered as part of a broad differential diagnosis of sinonasal tumors.

In-Hospital Endocrinology Consultation After Transsphenoidal Surgery: Is It Always Necessary?

BACKGROUND: Patients with sellar masses undergoing transsphenoidal surgery (TSS) frequently develop endocrine dysfunction; therefore, in-hospital endocrinology consultation (IHEC) is recommended. However, we wondered whether routine endocrinology assessment of all TSS patients is always necessary. METHODS: We developed an IHEC Physician's Guide to identify patients who would require peri-operative IHEC. An analysis of all patients undergoing TSS for a sellar mass over a 4-year period was conducted to assess the predictive value of the IHEC Physician's Guide in identifying patients who required IHEC. RESULTS: A total of 116 patients underwent TSS; 24 required IHEC. As expected, the risk of endocrine complications requiring peri-operative endocrine management was significantly higher in the IHEC group versus no-IHEC group (96% vs. 1%; p < 0.001). The negative predictive value of the IHEC Physician's Guide in identifying patients who did not require IHEC was 0.99 (95% CI 0.9409-0.9997); Fisher's exact test, p < 0.001), meaning that the IHEC Physician's Guide successfully identified all but one patient who truly required IHEC. CONCLUSION: Results from our study show that most patients do not need IHEC after TSS and that those patients requiring IHEC can be reliably predicted at surgery by using a simple IHEC Physician's Guide.

Securing the position of the nasoseptal flap in endoscopic transsphenoidal surgery: No need for a Foley catheter (technical report).

BACKGROUND: The pedicled nasoseptal mucoperiosteal flap is currently widely used for the reconstruction of a skull base defect following transsphenoidal surgery. The flap is generally secured in position by a Foley catheter balloon. We describe an alternative technique using cylinders of Gelfoam™ (Pfizer Incorporated) to buttress the flap in place, obviating the need for a balloon catheter. MATERIAL AND METHODS: A review of our database identified patients who underwent endoscopic transsphenoidal surgery for a pituitary macroadenoma with nasoseptal flap, secured with small rolls of Gelfoam™ (Pfizer Incorporated) rather than a nasal Foley catheter. Minimum follow-up clinical and MRI assessments: 3 months. RESULTS: 73 patients (mean follow-up: 22 months) met the inclusion criteria: 56 non-functioning and 17 functioning pituitary adenomas. 36 patients had an intraoperative CSF leak: 30 high flow and 6 low flow leaks. The surgical repair in 35 patients included fat +/- fascia graft. One patient had a post-operative CSF leak repaired by subsequent surgery without the use of a Foley catheter. CONCLUSION: Securing the nasoseptal flap using rolls of Gelfoam™ (Pfizer Incorporated) as described can be achieved without the use of a nasal Foley catheter.

Rhinitis medicamentosa: a nationwide survey of Canadian otolaryngologists.

BACKGROUND: Rhinitis medicamentosa is a non-allergic form of rhinitis that is typically caused by prolonged use of topical nasal decongestants. This condition commonly affects young adults and treatment is not trivial. We aimed to survey Canadian Otolaryngologists to determine practice patterns and their opinions regarding this under-studied condition. METHODS: An electronic survey was sent to practicing Otolaryngologists within the Canadian Society of Otolaryngology - Head and Neck Surgery. The survey contained 16 questions pertaining to the diagnosis and treatment of rhinitis medicamentosa, as well as opinions on public and primary care awareness of proper use of nasal decongestants. RESULTS: The survey was distributed to 533 Otolaryngologists and 69 surveys were returned (response rate of 13%). Cessation and weaning of decongestant (96%), and intranasal steroids (94%) were the most common methods for treating RM. Intranasal saline rinses (55%) and oral steroids (25%) were also supported by some respondents. For those who recommended cessation/weaning, 61% also concurrently introduced an intranasal steroid during this process. The majority responded that current warnings on nasal decongestants were inadequate (75%), and were not visible enough (79%). CONCLUSIONS: Rhinitis medicamentosa is a common, and very preventable condition. Although the literature lacks a standardized approach to RM, our survey has shown that many Otolaryngologists diagnose and treat RM in a similar manner. Treatment tends to focus on decongestant cessation, often with concurrent introduction of intranasal steroids. It was felt the warning labels on the topical medications are not currently satisfactory.

Cavernous sinus involvement in human papillomavirus associated oropharyngeal squamous cell carcinoma: case report of an atypical site of distant metastasis.

BACKGROUND: HPV-associated OSCC (HPV-OSCC) has been determined to be a distinct disease entity from non-HPV associated OSCC. Patients affected by HPV-OSCC generally have a more favourable prognosis, with improved rates of locoregional control and survival compared with their non-HPV counterparts. Despite this, HPV-OSCC has a similar rate of distant metastases. Interestingly, recent evidence has emerged that demonstrates more frequent atypical metastasis patterns when compared to non-HPV associated disease. To the best of our knowledge, this report describes the first case of a confirmed HPV-OSCC with distant metastasis to the cavernous sinus. CASE PRESENTATION: A 62-year-old non-smoking male presented to the head and neck oncology clinic with a five-month history of enlarging right neck mass causing neck pain, dysphagia, and dysphonia. HPV-associated base of tongue squamous cell carcinoma (cT4aN2c) was diagnosed, and he was treated with primary chemoradiation. Shortly after treatment, he presented with progressive bilateral cranial nerve palsies including left cranial nerve III and right cranial nerve VI involvement. Imaging identified masses in the left cavernous sinus with extension of tumor into the sella and in the right cavernous sinus at the level of Dorello's canal. Endoscopic Image Guided Transsphenoidal biopsy of the left sellar mass confirmed distant metastases from the previously treated HPV-OSCC primary to the cavernous sinus. The patient was palliated with carboplatin and paclitaxel. CONCLUSION: The presented report is the first documented case of confirmed HPV-associated oropharyngeal squamous cell carcinoma metastasizing to the cavernous sinus, and the only HPV confirmed head and neck cancer case to present with metastasis to the cavernous sinus and limited extracranial disease. This case demonstrates the importance of recognizing presentations of atypical metastasis that are possible in HPV-associated oropharyngeal cancer. Given the rarity of metastasis to this region, vigilance in follow up is instrumental in early identification and treatment for these patients.

Models for the study of nasal and sinus physiology in health and disease: A review of the literature.

Objective: Chronic sinusitis is a very common yet poorly understood medical condition with significant morbidity. Hence, it remains an entity that is difficult to treat with unsatisfactory outcomes of current management options. This necessitates research into the etiology and pathophysiology of the condition to enhance our knowledge and the therapeutic options. Unfortunately, this kind of research is not always feasible on human subjects due to practical and ethical limitations. Therefore, an alternative model that simulates the disease had to be found in order to overcome these limitations. These models could either be in vivo or in vitro. The aim of our review is to summarize the research findings and key discoveries of both in vivo and in vitro models of chronic sinusitis that have enhanced our understanding of the condition today and have paved the way for the future research of tomorrow. Data Sources: PubMed literature review. Methods: A review of the literature was conducted to identify the main successful in vivo and in vitro models for chronic sinusitis. Results: Creating a successful model for chronic sinusitis is no easy task. Over the years, both in vivo animal models and in vitro tissue culture models were proposed, with each model having its accolades and pitfalls, with the ideal model remaining elusive to this day. However, advancing three-dimensional cell culturing techniques seems to be a promising new way to find a more accurate model. Conclusion: None of the current models is perfect for a thorough study of chronic sinusitis. However, three-dimensional cell cultures have the potential to bridge the gap between in vivo and in vitro studies. Level of Evidence: NA.

Drug-eluting nasal implants: formulation, characterization, clinical applications and challenges.

Chronic inflammation and infection of the nasal sinuses, also referred to as Chronic Rhinosinusitis (CRS), severely affects patients' quality of life. Adhesions, ostial stenosis, infection and inflammation relapses complicate chronic sinusitis treatment strategies. Drug-eluting stents, packings or implants have been suggested as reasonable alternatives for addressing these concerns. This article reviewed potential drug candidates for nasal implants, formulation methods/optimization and characterization methods. Clinical applications and important considerations were also addressed. Clinically-approved implants (Propel™ implant, the Relieva stratus™ MicroFlow spacer, and the Sinu-Foam™ spacer) for CRS treatment was an important focus. The advantages and limitations, as well as future considerations, challenges and the need for additional research in the field of nasal drug implant development, were discussed.

An anatomically sound surgical simulation model for myringotomy and tympanostomy tube insertion.

OBJECTIVE: Myringotomy and tympanostomy tube insertion (MT) is a common surgical procedure. Although surgical simulation has proven to be an effective training tool, an anatomically sound simulation model for MT is lacking. We developed such a model and assessed its impact on the operating room performance of senior medical students. STUDY DESIGN: Prospective randomized trial. METHODS: A randomized single-blind controlled study of simulation training with the MT model versus no simulation training. Each participant was randomized to either the simulation model group or control group, after performing an initial MT procedure. Within two weeks of the first procedure, the students performed a second MT. All procedures were performed on real patients and rated with a Global Rating Scale by two attending otolaryngologists. Time to complete the MT was also recorded. RESULTS: Twenty-four senior medical students were enrolled. Control and intervention groups did not differ at baseline on their Global Rating Scale score or time to complete the MT procedure. Following simulation training, the study group received significantly higher scores (P=.005) and performed the MT procedure in significantly less time (P=.034). The control group did not improve their performance scores (P>.05) or the time to complete the procedure (P>.05). CONCLUSION: Our surgical simulation model shows promise for being a valuable teaching tool for MT for senior medical students. Such anatomically appropriate physical simulators may benefit teaching of junior trainees.

Organic cation transporters in human nasal primary culture: expression and functional activity.

BACKGROUND: The majority of drugs cross epithelial cells by either passive diffusion or via carrier-mediated drug transporters. The aim of this study was to investigate the transport characteristics, protein expression and localization of organic cation transporters in human nasal epithelium. METHODS & RESULTS: The expression, localization and transport characteristics of the transporters were investigated using permeation, PCR and immunohistochemistry. The uptake of 4-(4-(dimethylamino)styryl)-N-methylpyridinium iodide followed Michaelis-Menten kinetics. Its intracellular accumulation of the compound was inhibited by organic cation transporters (OCTs) and carnitine/organic cation transporter (OCTNs) inhibitors. Detected OCT1-3, OCTN1 and OCTN2 gene transcripts correlated with immunohistological staining for OCT1-3, OCTN1 and OCTN2 antibodies. Except for OCTN1, the antibodies were generally localized on the apical side of the epithelial cells. CONCLUSION: Based on the immunohistochemical and uptake/transport studies, we conclude that the human nasal epithelium expresses OCT1-3, OCTN1 and OCTN2 transporters mainly on the apical side of the nasal cells.

Optimization of human nasal epithelium primary culture conditions for optimal proton oligopeptide and organic cation transporters expression in vitro.

AIM: To investigate the effect of key tissue culture conditions on cell growth, gene expression and functional uptake of peptide and organic cation transporter substrates in the human nasal epithelium (HNE). METHODS: HNE were cultured on different growth surfaces (polystyrene plastic, collagen film, and hydrated collagen gel) and were maintained with three popular nasal tissue culture media supplements [DMEM/F12 supplemented with Ultroser(®) G (2%), FBS (10%) and NuSerum(®) (10%)], respectively. The expression of gene transcripts for organic cation and peptide transporters were screened using qPCR and substrate uptake studies. RESULTS: Cell growth surface (polystyrene plastic surface, dried collagen film and hydrated collagen gel) did not significantly alter gene expression levels. However, Ultroser(®) G and FBS caused significant increase in PEPT1, PEPT2, PHT1, OCT3, and OCTN1 levels (~/=2-5-fold for FBS and 2-8-fold for Ultroser(®) G). In terms of the degree to which the supplements affected gene expression, the following observations were made: effect on OCTN1>PEPT2>OCT3>PHT1>PEPT1. Functional uptake of organic cation (4-Di-1-ASP) and peptide [ß-Ala-Lys (AMCA)] transporter substrates was significantly lower in cells cultured with NuSerum(®) compared to Ultroser(®) G and FBS cultured cells (p>0.05). CONCLUSIONS: Tissue culture media had a major effect on SLC gene expression levels of the human nasal epithelium in primary culture. Ultroser(®) G was identified as the most efficient culture supplement in maintaining SLC transporter expression under most culture conditions, whereas FBS appears to be an economical choice. We do not recommend the use of NuSerum(®) as a supplement for growing HNE for transport studies involving SLC transporters.

Systematic evaluation of obstructive sleep apnea websites on the internet.

OBJECTIVE: To determine the quality and comprehensiveness of the websites on the Internet with information directed toward patients with obstructive sleep apnea (OSA). DESIGN: Systematic evaluation of websites on the Internet with information on OSA. SETTING: World Wide Web. METHODS: The search engine Google was queried with the term "obstructive sleep apnea." The first 50 results were evaluated. Only websites written in English and containing original information were reviewed. MAIN OUTCOME MEASURES: A data quality score (DQS) was generated by evaluating each website for the presence of 67 points of information relating to OSA. Each website was also evaluated using a Global Quality Score (GQS), the DISCERN instrument, the Flesch-Kincaid reading grade level, date of the last update, and sources of funding. RESULTS: Thirty-four websites met the inclusion criteria. The average DQS was 36 points (range 17-57). The average GQS was 2.9 (range 1-5). The average DISCERN score was 3.3 (range 1.9-4.7). The average reading grade level was 11.0 (range 5.0-15.8). Twenty-six websites (76%) provided authorship information. Twenty-five websites (74%) displayed a date of the last update. Of these, 12 websites were not updated within the past 2 years. Twenty websites (59%) provided a source of funding. CONCLUSIONS: There is a heterogeneous mixture of websites with varying quality on the Internet with information regarding OSA. Health care providers should be cognizant of the variety of information available for patients and be prepared to direct patients toward the high-quality information sources.

Proton-coupled oligopeptide transporter (POT) family expression in human nasal epithelium and their drug transport potential.

The molecular and functional expression of peptide transporters (PEPT1 and PEPT2, PHT1, PHT2) in human nasal epithelium was investigated. Quantitative/reverse transcriptase polymerase chain reaction (qPCR/RT-PCR), Western blotting and indirect immuno-histochemistry were used to investigate the functional gene and protein expression for the transporters. Uptake and transport studies were performed using metabolically stable peptides [ß-alanyl-L-lysyl-Nε-7-amino-4-methyl-coumarin-3-acetic acid (ß-Ala-Lys-AMCA) and ß-alanyl-L-histidine (carnosine)]. The effects of concentration, temperature, polarity, competing peptides, and inhibitors on peptide uptake and transport were investigated. PCR products corresponding to PEPT1 (150 bp), PEPT2 (127 bp), PHT1 (110 bp) and PHT2 (198 bp) were detected. Immunohistochemistry and Western blotting confirmed the functional expression of PEPT1 and PEPT2 genes. The uptake of ß-Ala-Lys-AMCA was concentration-dependent and saturable (Vmax =4.1 ( 0.07 µmol/min/mg protein, Km = 0.6 ( 0.07 µM). The optimal pH for intracellular accumulation of ß-Ala-Lys-AMCA was 6.5. Whereas dipeptides and carbonyl cyanide m-chlorophenylhydrazone (CCCP) significantly inhibited peptide uptake and transport, L-Phe had no effect on peptide transport. The permeation of ß-alanyl-L-histidine was concentration-, direction-, and temperature-dependent. The uptake, permeation, qPCR/RT-PCR and protein expression data showed that the human nasal epithelium functionally expresses proton-coupled oligopeptide transporters.

Differential expression of organic cation transporters in normal and polyps human nasal epithelium: implications for in vitro drug delivery studies.

The aim of this study was to compare the expression of organic cation transporters (OCTs) in normal and polyps nasal epithelium. Primary cell cultures of human nasal epithelium (polyps and normal tissues) were compared by investigating the uptake of a fluorescent organic cation, [4-dimethylaminostyryl-N-methylpyridinium (4-Di-1-ASP)]. The effect of concentration, temperature, pH and competing inhibitors were investigated. Quantitative polymerase chain reaction (qPCR) was used to compare the OCTs gene expression levels in the cells. The K(m) (µM) and V(max) (µM/mg protein/15 min) for 4-Di-1-ASP uptake were higher in normal (K(m)=3031 ± 559.6, V(max)=70.8 ± 8.8) cells compared to polyps (K(m)=952.4 ± 207.8, V(max)=30.9 ± 2.1). qPCR results showed that OCT1-3 and organic cation/carnitine transporter 1-2 gene transcripts (OCTN1-2) were expressed in both normal and polyps cells at comparable levels, with OCT-3 having the highest expression level in both cultures. Kruskal-Wallis ANOVA showed that pH and specific inhibitors had similar effects on both normal and polyps cells (p>0.5). Similarly, OCTs and OCTNs gene expression levels were similar. This study showed that polyps biopsies can be used for isolating cells to study organic cation transporters in human nasal epithelium as no major functional or molecular differences relative to normal cells could be found.

Carotid artery visualization during anterior skull base surgery: a novel protocol for neuronavigation.

Detailed knowledge of the vascular anatomy of the anterior skull base is critical to successful surgery in this area. Whereas conventional neuronavigational approaches combine MRI (+/- contrast) for tumor visualization and CT (+/- C) for bony and vascular anatomy, we describe the Canadian and Austrian experiences using a novel protocol integrating MR angiography (MRA) into surgical neuronavigation to provide superior visualization of the carotid arteries. The pre-operative imaging protocol employs a T1-weighted, 3D fast spoiled gradient echo MRI (+/- C) for soft tissue anatomy, a plain CT for bony anatomy, and a 3D time-of-flight MR angiography for carotid anatomy. The series are imported into the Medtronic StealthStation((R)) TREON((R)) Treatment Guidance System; during intra-operative neuronavigation, each series (MRI, CT, MRA) can be viewed individually, or layered and viewed as a composite image. Our protocol has important advantages. First, it provides detailed tissue, tumor, vascular and bony anatomy. Second, a contrast CT is not necessary; this is important, as numerous reports have highlighted the nephrotoxic nature of radiographic contrast material. Third, visualization of the carotid system is superior than can be obtained from CT angiography. We use this unique imaging protocol routinely for our endoscopic transsphenoidal surgeries to provide superior visualization of the carotid arteries during anterior skull base surgery.

Specific aminopeptidases of excised human nasal epithelium and primary culture: a comparison of functional characteristics and gene transcripts expression.

OBJECTIVES: To investigate whether growing human nasal epithelium as primary cultures alters aminopeptidase B (APB), aminopeptidase N (APN) and dipeptidyldipeptidase (DPPIV) metabolic characteristics, and mRNA gene transcript expression. METHODS: The formation of 7-amino-methyl coumarin from specific substrates for APN (L-alanine-4-methyl-coumaryl-7-amide, APB (L-arginine-4-methyl-coumaryl-7-amide) and DPPIV (glycyl-L-proline-4-methyl-coumaryl-7-amide) was used to estimate the KM, Vmax and the effect of aminopeptidases inhibitors on the enzymes. Polymerase chain reaction was used to investigate gene expression. KEY FINDINGS: Results of this study showed that: (1) both the excised tissues and primary cultures of human nasal epithelium expressed APN, APB and DPPIV activity; (2) the KM of APB, APN and DPPIV was not significantly different in cell and tissue homogenates; (3) except for APN, the Vmax was not significantly different in the two metabolism models; (4) there was no statistically significant difference in the behaviours of APB, APN and DPPIV in response to inhibition by puromycin and bestatin in the two models; (5) the mRNA transcripts that encode APB, APN and DPPIV were expressed in both cell culture and tissue homogenate. CONCLUSIONS: Based on the results of this study, it may be concluded that nasal primary culture system is suitable for investigating peptide and protein metabolism and enzymatic stability in human nasal epithelium. Except for APN, the tissue culture conditions did not significantly alter the functional and molecular expression of the aminopeptidases.

Quality of life and impact of surgery on patients with chronic rhinosinusitis.

OBJECTIVE: To measure the impact of chronic rhinosinusitis (CRS) on the health of Nova Scotians and evaluate the role of surgery in modifying this impact. METHODS: Nova Scotia residents with CRS referred to one otolaryngologist were enrolled. The Chronic Sinusitis Survey (CSS) and Short Form 36-Item Health Survey (SF-36) were administered preoperatively and at two postoperative visits. The SF-36 data were compared with Canadian published norms. Also, the postoperative survey results were compared with preoperative data to evaluate the role of surgery in improving health. RESULTS: Thirty-eight patients completed preoperative and 3-month forms, and 26 patients completed preoperative and 3- and 12-month postoperative forms. Patients with CRS showed a significant decrease in five of eight SF-36 subscales. Surgery significantly improved preoperative scores for six of eight subscales and both the physical (PCS) and mental (MCS) component summary scores (p < .05). Males were more likely than females to report postoperative improvements (p = .02). Males under 50 years were more likely to show improvement in the PCS score (p = .02), with no significant change in the MCS score. Females under 50 years were more likely to show improvement in the MCS score (p = .02), with age having no effect on PCS score. CONCLUSION: This study confirms that Canadians with CRS have lower quality of life and for the first time in Canada demonstrates that functional endoscopic sinus surgery can restore health. Males showed a greater response than females, and patients under 50 years were more likely to improve after surgery. This information on patient factors influencing outcomes may help physicians when counseling patients regarding surgery for CRS.

The health and resource utilization of Canadians with chronic rhinosinusitis.

OBJECTIVES: To determine the impact of chronic rhinosinusitis (CRS) on the physical and mental health and health-resource utilization of Canadians. STUDY DESIGN: Cross-sectional. METHODS: Data from the detailed health portion of cycle 3 (1998-1999) of the National Population Health Survey (NPHS), which involved 17,000 Canadians, were used to evaluate Canadians with self-reported CRS. RESULTS: NPHS data confirmed lower mental and physical health, with CRS sufferers being almost three times more likely to report their health as poor (4.6% vs. 1.7%). Health Utility Index data identified a significant decline in the mental health of patients with CRS, which was associated with more depression (8.4% vs. 4.1%), more antidepressant use (9.1% vs. 4.6%), and more visits to mental-health professionals (11.8% vs. 7.0%). CONCLUSIONS: CRS significantly affects both physical and mental health. The mental impact of CRS remains largely unrecognized and should be of greater focus during patient care and in further research.