- Cancer > Head and Neck Cancer
- Chronic Rhinosinusitis
- Endoscopic Sinus Surgery
- Endoscopic Skullbase Surgery
- Nasal Septum and Turbinate Surgery
- Empty Nose Syndrome
- Epiphora/Excessive Tearing Surgery
- Epistaxis/Nosebleed Disorders and Surgery
- Clivus/Foramen Magnum/Odontoid Surgery
- All Varieties of Rhinologic/Sinus Disorders
- Revision Nasal Airway and Sinus Surgery
Assistant Professor - Med Center Line, Otolaryngology - Head & Neck Surgery Divisions
Assistant Professor - Med Center Line (By courtesy), Neurosurgery
Co-Director, Rhinology Fellowship Training Program, Stanford Dept. of Otolaryngology (2011 - 2018)
Honors & Awards
Co-Valedictorian, Woodbridge High School, New Jersey (1988)
Baccalaureate with Honors, University of Pennsylvania (1992)
Stanley J. Sarnoff Endowment Medical Student Research Fellowship, Salk Institute, La Jolla, CA (1994)
Howard Hughes Medical Institute Medical Student Research Fellowship, U California, San Diego (1995)
American Heart Association Medical Student Research Fellowship, U Californioa, San Diego (1996)
M.D./Ph.D. Transfer Admission & Full Scholarship Award, University of Pittsburgh (1997)
Bernhard A. Goldman Prize in Dermatology, University of Pittsburgh (2003)
Gold Foundation Little Apple Medical Student Teaching Award Finalist, University of Pittsburgh (2004)
CORE Schering Plough Resident Research Award from the American Academy of Otolaryngology, University of Pittsburgh (2005)
Influenza virus tropism for human nasal epithelial cells of the upper airway, Marion Avery Family Grant (2012)
2D and 3D Electron Microscopy Ultrastructure of Murine Nasal Cavity, Stanford Beckman Center Technology Innovation MiniGrant program (2012)
Immune Responses to Influenza Virus in Single Human Nasal Epithelial Cells, NIH/Cooperative Centers for Translational Research on Human Immunology and Biodefense (CCHI) (2012)
Human Mucosal Immune Responses to Influenza Virus: a Systems Biology Approach, NIH/Human Immunology Project Consortium (HIPC) (2012)
Career Development Award - Basal cells in maintenance and regeneration of the nasal epithelium, Triological Society of the American Academy of Otolaryngology-Head and Neck Surgery (2012)
National Finalist - Clinical Scientist Development Award, Doris Duke Charitable Foundation (December 2014)
Board Certification: Otolaryngology, American Board of Otolaryngology (2010)
Fellowship:University of Pennsylvania (2009) PA
Residency:University of Pittsburgh Medical Center (2008) PA
Internship:University of Pittsburgh Medical Center (2004) PA
M.D., Ph.D., University of Pittsburgh School of Medicine, MD - General Medicine PhD - Immunology (2003)
Medical Education:University of Pittsburgh School of Medicine (2003) PA
B.A., University of Pennsylvania, Neuroscience (1992)
Randall Kesten, Howard Levine, Thomas R. Jenkins, Jessica M. Liberatore and Jayakar V. Nayak. "United States Patent 9,433,347 Apparatus and ethmoid for treatment of ethmoid sinusitis", Sep 6, 2016
Current Research and Scholarly Interests
Upper Airway Stem Cell Biology, Fate, and Repair/Regeneration of the Airway Epithelium to treat Upper and Lower Airway Disorders
Independent Studies (9)
- Directed Reading in Immunology
IMMUNOL 299 (Win, Spr)
- Directed Reading in Otolaryngology
OTOHNS 299 (Aut, Win, Spr, Sum)
- Early Clinical Experience in Immunology
IMMUNOL 280 (Win, Spr)
- Graduate Research
IMMUNOL 399 (Win, Spr)
- Graduate Research
OTOHNS 399 (Aut, Win, Spr, Sum)
- Medical Scholars Research
OTOHNS 370 (Aut, Win, Spr, Sum)
- Teaching in Immunology
IMMUNOL 290 (Win, Spr)
- Undergraduate Research
IMMUNOL 199 (Win, Spr)
- Undergraduate Research
OTOHNS 199 (Aut, Win, Spr, Sum)
- Directed Reading in Immunology
Graduate and Fellowship Programs
Surgical therapy vs continued medical therapy for medically refractory chronic rhinosinusitis: a systematic review and meta-analysis.
International forum of allergy & rhinology
2017; 7 (2): 119-127
The currently accepted treatment paradigm of treating chronic rhinosinusitis (CRS) first with appropriate medical therapy (AMT) and then with surgery if patients are refractory to AMT, has been criticized for lack of evidence. The objective of this study was to reassess the literature and establish the highest level of evidence possible regarding further management of CRS patients refractory to AMT.This study was a systematic review (SR) with meta-analysis (MA). Adult CRS patients who received AMT and then underwent either medical or surgical therapy in moderate to high level prospective studies were included. Outcomes assessed were disease-specific quality of life (QOL), nasal endoscopy, health-state utility, missed work days, change in cardinal symptoms of CRS, economic impact, and adverse events.A total of 970 manuscripts were identified; 6 studies were ultimately included in the SR with 5 included in the MA. Compared to continued medical therapy, endoscopic sinus surgery (ESS) significantly improved patient-based QOL scores (p < 0.00001) and nasal endoscopy scores (p < 0.00001). Difference in missed work days depended heavily on patient choice of intervention. Unpooled analysis showed improvements in olfaction, health utility scores, and cost-effectiveness.On meta-analysis, for CRS patients refractory to AMT, ESS significantly improves objective endoscopic scoring outcomes vs continued medical therapy alone. In patients with refractory CRS who have significant reductions in baseline QOL, ESS results in significant improvements. Continued medical therapy appears to maintain outcomes in patients with less severe baseline QOL. Unpooled analysis demonstrates improvement in health utility, olfaction, and cost-effectiveness following ESS compared to continued medical therapy alone, in medically refractory CRS.
View details for DOI 10.1002/alr.21872
View details for PubMedID 27863163
Wnt Signaling in Chronic Rhinosinusitis with Nasal Polyps.
American journal of respiratory cell and molecular biology
The signaling pathways that sustain the disease process of chronic rhinosinusitis with nasal polyps (CRSwNP) remain poorly understood. We sought to determine the expression levels of Wnt signaling genes in CRSwNP and to study the role of the Wnt pathway in inflammation and epithelial remodeling in the nasal mucosa. Microarrays and real time-quantitative polymerase chain reaction comparing gene expression in matched NPs and inferior turbinates revealed that WNT2B, WNT3A, WNT4, WNT7A, WNT7B, and FZD2 were up-regulated and that FZD1, LRP5, LRP6, and WIF1 were down-regulated in NPs. Immunolabeling showed robust expression of Wnt ligands, nuclear β-catenin, and Axin-2 in NP tissue, suggesting that Wnt/β-catenin signaling is activated in NPs. We used primary human nasal epithelial cell (HNEpC) cultures to test the functional consequences of Wnt pathway activation. Monolayer HNEpCs treated with recombinant human WNT (rhWNT) 3A, but not with rhWNT4, had altered epithelial morphology and decreased adhesion, without loss of viability. We found that neither rhWNT3A nor rhWNT4 treatment induced proliferation. The expression and release of inflammatory cytokines IL-6 and granulocyte-macrophage colony-stimulating factor were increased after rhWNT3A exposure of HNEpCs. When differentiated at an air-liquid interface, rhWNT3A- and WNT agonist-, but not rhWNT4-treated HNEpCs, had abnormal epithelial architecture, failed to undergo motile ciliogenesis, and had defective noncanonical Wnt (planar cell polarity) signaling. On the basis of these results, we propose a model in which Wnt/β-catenin signaling sustains mucosal inflammation and leads to a spectrum of changes consistent with those seen during epithelial remodeling in NPs.
View details for DOI 10.1165/rcmb.2016-0024OC
View details for PubMedID 28059551
Endoscopic Resection of Skull Base Teratoma in Klippel-Feil Syndrome through Use of Combined Ultrasonic and Bipolar Diathermy Platforms.
Case reports in otolaryngology
2017; 2017: 6384586-?
Klippel-Feil syndrome (KFS) is associated with numerous craniofacial abnormalities but rarely with skull base tumor formation. We report an unusual and dramatic case of a symptomatic, mature skull base teratoma in an adult patient with KFS, with extension through the basisphenoid to obstruct the nasopharynx. This benign lesion was associated with midline palatal and cerebral defects, most notably pituitary and vertebrobasilar arteriolar duplications. A multidisciplinary workup and a complete endoscopic, transnasal surgical approach between otolaryngology and neurosurgery were undertaken. Out of concern for vascular control of the fibrofatty dense tumor stalk at the skull base and need for complete teratoma resection, we successfully employed a tissue resection tool with combined ultrasonic and bipolar diathermy to the tumor pedicle at the sphenoid/clivus junction. No CSF leak or major hemorrhage was noted using this endonasal approach, and no concerning postoperative sequelae were encountered. The patient continues to do well now 3 years after tumor extirpation, with resolution of all preoperative symptoms and absence of teratoma recurrence. KFS, teratoma biology, endocrine gland duplication, and the complex considerations required for successfully addressing this type of advanced skull base pathology are all reviewed herein.
View details for DOI 10.1155/2017/6384586
View details for PubMedID 28133560
View details for PubMedCentralID PMC5241474
Distinguishing computed tomography findings in patients with empty nose syndrome.
International forum of allergy & rhinology
2016; 6 (10): 1075-1082
Given the lack of basic diagnostic criteria for empty nose syndrome (ENS), we sought to define whether consistent radiographic characteristics could be identified to aid in the development of such criteria.Computed tomography (CT) scans were collected from 65 patients diagnosed with ENS, patients with a history of submucosal inferior turbinate reduction (ITR) without ENS, and patients without a history of sinonasal procedures. Measurements were taken at the level of the nasolacrimal duct, including the inferior turbinate (IT) mucosal thickness, and the widest distances between septum-IT, nasal floor-IT, lateral nasal wall-IT, and septum-lateral nasal wall. The thickest sites of soft tissue density of the nasal cavity floor, septum, and lateral wall were also measured in the anterior, central, and posterior segments of the nasal cavity.The mucosal thickness of both the central and posterior segments of the septum in ENS subjects was significant when compared to ITR without ENS (p < 0.01) and control subjects (p < 0.01). Constant landmarks such as the agger nasi, the presence of middle turbinate, and the nasolacrimal duct defined a simple set of landmarks that can serve as the start of the central-nasal region, and a cutoff >2.64 mm and >1.32 mm in the central nasal and posterior nasal regions provided the highest likelihood of differentiating ENS patients from ITR without ENS patients.These findings provide evidence there are 2 objective radiographic changes (central and posterior septal mucosa) that suggest ENS patients can be discriminated based on mucosal CT findings.
View details for DOI 10.1002/alr.21774
View details for PubMedID 27409044
Airway epithelial homeostasis and planar cell polarity signaling depend on multiciliated cell differentiation.
2016; 1 (13)
Motile airway cilia that propel contaminants out of the lung are oriented in a common direction by planar cell polarity (PCP) signaling, which localizes PCP protein complexes to opposite cell sides throughout the epithelium to orient cytoskeletal remodeling. In airway epithelia, PCP is determined in a 2-phase process. First, cell-cell communication via PCP complexes polarizes all cells with respect to the proximal-distal tissue axis. Second, during ciliogenesis, multiciliated cells (MCCs) undergo cytoskeletal remodeling to orient their cilia in the proximal direction. The second phase not only directs cilium polarization, but also consolidates polarization across the epithelium. Here, we demonstrate that in airway epithelia, PCP depends on MCC differentiation. PCP mutant epithelia have misaligned cilia, and also display defective barrier function and regeneration, indicating that PCP regulates multiple aspects of airway epithelial homeostasis. In humans, MCCs are often sparse in chronic inflammatory diseases, and these airways exhibit PCP dysfunction. The presence of insufficient MCCs impairs mucociliary clearance in part by disrupting PCP-driven polarization of the epithelium. Consistent with defective PCP, barrier function and regeneration are also disrupted. Pharmacological stimulation of MCC differentiation restores PCP and reverses these defects, suggesting its potential for broad therapeutic benefit in chronic inflammatory disease.
View details for PubMedID 27570836
Characterization of immunoglobulin E plasma cells that are elevated in the upper airway mucosa of nonatopic patients with chronic rhinosinusitis without nasal polyps
INTERNATIONAL FORUM OF ALLERGY & RHINOLOGY
2016; 6 (4): 378-384
The immunologic mechanisms driving inflammation in the upper airways of patients with chronic rhinosinusitis (CRS) are poorly understood. Previous studies have shown that B cells and immunoglobulin E (IgE) levels are elevated in the nasal tissue of patients with atopic chronic rhinosinusitis without nasal polyps (CRSsNP). However, less is known regarding B cell subsets and IgE-producing plasmablasts in nonatopic CRSsNP patients.Human blood and ethmoid sinus mucosa samples were analyzed from control (n = 6) and nonatopic CRSsNP (n = 11) patients. Tissue samples were evaluated using high-dimensional flow cytometry.A population of IgE antibody secreting cells is significantly increased in situ within inflamed nasal tissue of nonatopic CRSsNP subjects when compared to control nasal tissue and the circulating peripheral blood (p < 0.05). This IgE plasma cell population displays ∼90% cell surface Ig lambda light chain, is mitotically active (Ki-67(+) ), and displays intracellular IgE expression. The predominant B cell population expressing IgE are plasmablasts (CD38(high) , CD138(-) ) not typically found in the blood or peripheral tissue of these patients.The nasal mucosa from nonatopic CRSsNP patients demonstrate a significant regional spike in resident in situ IgE plasmablast cells not seen in control nasal tissue or peripheral blood from the same patient. The restricted expression of Ig lambda light chain in this mitotically active IgE plasmablast population supports the hypothesis of aberrant B cell proliferation in the context of CRS. These findings suggest the presence of a unique regional immune microenvironment for B cell priming and/or selection within chronically inflamed airway tissues.
View details for DOI 10.1002/alr.21696
View details for Web of Science ID 000373618500007
View details for PubMedID 26878990
Use of Pedicled Nasoseptal Flap for Pathologic Oroantral Fistula Closure.
Journal of oral and maxillofacial surgery
2016; 74 (4): 704 e1-6
Oroantral fistula (OAF) is a pathologic, epithelialized communication between the oral cavity and the maxillary sinus. OAF most commonly results from posterior maxillary tooth or molar extraction owing to proximity of the dental roots to the maxillary antrum and the thinness of the adjacent antral floor. It also can arise secondary to implant and orthognathic surgeries, cyst and tumor removal, dental infection, trauma, or as a sequela of radiation therapy. Communications larger than 5 mm are less likely to heal spontaneously and can epithelialize, forming an OAF. When locoregional flaps and grafts are not ideal or have failed, but primary OAF closure is mandated, surgical options are unclear. This report describes a novel method for autologous tissue flap coverage from the nasal septum, pedicled off the posterior septal artery, for successful extension to, and closure of, OAFs.
View details for DOI 10.1016/j.joms.2015.11.010
View details for PubMedID 26704432
The nasal vestibular body: anatomy, clinical features, and treatment considerations
EUROPEAN ARCHIVES OF OTO-RHINO-LARYNGOLOGY
2016; 273 (3): 777-781
Nasal obstruction is a common presenting complaint, with many possible etiologies. Herein, we provide an introductory anatomic description, clinical relevance, and proposed nomenclature for an underappreciated soft tissue focus in the nasal vestibule-the nasal vestibular body (NVB)-that can contribute to nasal obstruction in a subset of patients. This is a small mound of dynamic soft tissue in the lateral aspect of the internal nasal valve, situated inferior and anterior to the head of the inferior turbinate that can be missed on routine examination for many salient reasons. In well-selected patients, whose symptoms of nasal obstruction may in part be secondary to the presence of this soft tissue focus, directed testing and tissue reduction can be performed.
View details for DOI 10.1007/s00405-015-3868-2
View details for Web of Science ID 000371063700035
View details for PubMedID 26825801
International Consensus Statement on Allergy and Rhinology: Rhinosinusitis
INTERNATIONAL FORUM OF ALLERGY & RHINOLOGY
2016; 6: S22-S209
Isam Alobid, MD, PhD(1) , Nithin D. Adappa, MD(2) , Henry P. Barham, MD(3) , Thiago Bezerra, MD(4) , Nadieska Caballero, MD(5) , Eugene G. Chang, MD(6) , Gaurav Chawdhary, MD(7) , Philip Chen, MD(8) , John P. Dahl, MD, PhD(9) , Anthony Del Signore, MD(10) , Carrie Flanagan, MD(11) , Daniel N. Frank, PhD(12) , Kai Fruth, MD, PhD(13) , Anne Getz, MD(14) , Samuel Greig, MD(15) , Elisa A. Illing, MD(16) , David W. Jang, MD(17) , Yong Gi Jung, MD(18) , Sammy Khalili, MD, MSc(19) , Cristobal Langdon, MD(20) , Kent Lam, MD(21) , Stella Lee, MD(22) , Seth Lieberman, MD(23) , Patricia Loftus, MD(24) , Luis Macias-Valle, MD(25) , R. Peter Manes, MD(26) , Jill Mazza, MD(27) , Leandra Mfuna, MD(28) , David Morrissey, MD(29) , Sue Jean Mun, MD(30) , Jonathan B. Overdevest, MD, PhD(31) , Jayant M. Pinto, MD(32) , Jain Ravi, MD(33) , Douglas Reh, MD(34) , Peta L. Sacks, MD(35) , Michael H. Saste, MD(36) , John Schneider, MD, MA(37) , Ahmad R. Sedaghat, MD, PhD(38) , Zachary M. Soler, MD(39) , Neville Teo, MD(40) , Kota Wada, MD(41) , Kevin Welch, MD(42) , Troy D. Woodard, MD(43) , Alan Workman(44) , Yi Chen Zhao, MD(45) , David Zopf, MD(46) CONTRIBUTING AUTHOR AFFILIATIONS: (1) Universidad de Barcelona; (2) University of Pennsylvania; (3) Louisiana State University Health Sciences Center; (4) Universidade de São Paulo; (5) ENT Specialists of Illinois; (6) University of Arizona; (7) University of Oxford; (8) University of Texas; (9) University of Indiana; (10) Mount Sinai Beth Israel; (11) Emory University; (12) University of Colorado; (13) Wiesbaden, Germany; (14) University of Colorado; (15) University of Alberta; (16) University of Alabama at Birmingham; (17) Duke University; (18) Sungkyunkwan University; (19) University of Pennsylvania; (20) Universidad de Barcelona; (21) Northwestern University; (22) University of Pittsburgh; (23) New York University; (24) Emory University; (25) University of British Columbia; (26) Yale University School of Medicine; (27) Private Practice; (28) Department of Otolaryngology, Hôtel-Dieu Hospital, Centre de Recherche du Centre Hospitalier de l'Université de Montréal; (29) University of Adelaide; (30) Pusan National University; (31) University of California, San Francisco; (32) University of Chicago; (33) University of Auckland; (34) Johns Hopkins University; (35) University of New South Wales, Australia; (36) Stanford University; (37) Washington University; (38) Harvard Medical School; (39) Medical University of South Carolina; (40) Singapore General Hospital; (41) Taho University; (42) Northwestern University; (43) Cleveland Clinic Foundation; (44) University of Pennsylvania; (45) University of Adelaide; (46) University of Michigan.
View details for DOI 10.1002/alr.21695
View details for Web of Science ID 000371151900002
View details for PubMedID 26889651
- Inferior turbinate reconstruction using porcine small intestine submucosal xenograft demonstrates improved quality of life outcomes in patients with empty nose syndrome INTERNATIONAL FORUM OF ALLERGY & RHINOLOGY 2015; 5 (11): 1077-1081
Medical therapy vs surgery for recurrent acute rhinosinusitis.
International forum of allergy & rhinology
2015; 5 (8): 667-673
Treatment indications for recurrent acute rhinosinusitis (RARS) remain poorly defined. We studied outcomes of medical vs surgical treatment of RARS, anatomic variants associated with RARS, and factors predicting crossover from medical to surgical treatment.A total of 220 RARS patients treated between 2006 and 2014 were retrospectively divided into 3 cohorts: medical only (MED); surgical only (SURG); or medical crossing over into surgical (CROSS). Twenty-two item Sino-Nasal Outcome Test (SNOT-22) scores, modified Lund-Kennedy endoscopy scores, and prevalence of anatomic variants by computed tomography (CT) were compared. A total of 220 CT scans obtained for non-sinus indications served as controls. A logistic regression model was used for analysis.The mean baseline SNOT-22 scores for all cohorts were similar (MED = 48, SURG = 49, CROSS = 45, p < 0.0001). The SURG cohort showed greater reduction of SNOT-22 scores compared to the MED cohort at 3, 6, and 12 months follow-up (p < 0.0001). The crossover cohort converted to surgery after escalation of SNOT-22 score by a mean of 15 points (p < 0.03), and showed significant reduction postoperatively (p < 0.0001). Haller cell (odds ratio [OR] 3.9; p < 0.0001), concha bullosa (OR 3.7; p < 0.003), and accessory ostium (OR 2.2; p < 0.01) were more common in the entire RARS group vs controls; however, there were no inter-cohort differences in prevalence.RARS patients can benefit from both medical and surgical treatment strategies, but surgical treatment results in greater symptomatic improvement compared to medical treatment. Patients cross over from medical to surgical treatment when SNOT-22 scores escalate by a mean of 15 points. Haller cell, concha bullosa, and accessory ostium are associated with RARS but are equally common in medical, surgical, and crossover cohorts.
View details for DOI 10.1002/alr.21533
View details for PubMedID 25950995
Endoscopic Transnasal Approach for Urgent Decompression of the Craniocervical Junction in Acute Skull Base Osteomyelitis.
Journal of neurological surgery reports
2015; 76 (1): e37-42
Ventral epidural abscess with osteomyelitis at the craniocervical junction is a rare occurrence that typically mandates spinal cord decompression via a transoral approach. However, given the potential for morbidity with transoral surgery, especially in the setting of immunosuppression, together with the advent of extended endonasal techniques, the transnasal approach could be attractive for selected patients. We present two cases of ventral epidural abscess and osteomyelitis at the craniocervical junction involving C1/C2 that were successfully treated via the endoscopic transnasal approach. Both were treated in staged procedures involving posterior cervical fusion followed by endoscopic transnasal resection of the ventral C1 arch and odontoid process for decompression of the ventral spinal cord and medulla. Dural repairs were successfully performed using multilayered, onlay techniques where required. Both patients tolerated surgery exceedingly well, had brief postoperative hospital stays, and recovered uneventfully to their neurologic baselines. Postoperative magnetic resonance imaging confirmed complete decompression of the foramen magnum and upper C-spine. These cases illustrate the advantages and low morbidity of the endonasal endoscopic approach to the craniocervical junction in the setting of frank skull base infection and immunosuppression, representing to our knowledge a unique application of this technique to osteomyelitis and epidural abscess at the craniocervical junction.
View details for DOI 10.1055/s-0034-1395492
View details for PubMedID 26251807
Intraocular Pressure Changes in Emergent Surgical Decompression of Orbital Compartment Syndrome
JAMA OTOLARYNGOLOGY-HEAD & NECK SURGERY
2015; 141 (6): 562-565
Orbital compartment syndrome is an acute rise in intraorbital volume resulting in increased intraorbital pressure and possible ischemic compromise of the optic nerve. Tonometric pressure measurement of intraocular pressure can aid surgeons in the diagnosis of this condition and in choosing the need to proceed with emergent surgical intervention. In addition, we present an unexpected cause of orbital compartment syndrome following routine frontal sinus irrigation.An emergent lateral canthotomy and cantholysis followed by endoscopic medial wall decompression were performed, with intraocular pressure measurements performed throughout the evolution of this successful, and vision sparing, set of procedures. The techniques and continuous improvements in intraocular pressure measurements are described.There are only rare reports of the progression of intraocular pressure prior to, and concurrent with, surgical orbital decompression. While no absolute threshold for intraocular pressure exists for when surgical decompression should be performed, the decision of when and which decompression procedures to undertake should be based on clinical judgment and experience. Availability of tonometry in the operating room serves to measure response to management in these rare but challenging settings where intervention may be required to prevent irreversible visual loss.
View details for DOI 10.1001/jamaoto.2015.0524
View details for Web of Science ID 000356458300012
View details for PubMedID 25880995
Clinical predictors of neo-osteogenesis in patients with chronic rhinosinusitis.
International forum of allergy & rhinology
2015; 5 (4): 303-309
Neo-osteogenesis of the paranasal sinuses is a radiologic finding of unclear clinical significance. Although current evidence suggests that these bony changes represent an inflammatory response rather than an infectious osteitis, bacteria associated with the sinonasal mucosa may induce inflammatory mediators as a mechanism of neo-osteogenesis. The objectives of this study were (1) to determine whether there is an association between bacteria isolated on sinus culture and neo-osteogenesis, and (2) to identify other predictive factors for neo-osteogenesis.Ninety patients undergoing sinus surgery for medically refractory CRS were recruited. Radiologic evidence of neo-osteogenesis was assessed by the Global Osteitis Scoring Scale (GOSS) and mucosal disease severity was assessed by the Lund-Mackay score (LMS). Bacterial culture was obtained endoscopically at the preoperative office visit or during surgery. Multiple and logistic regression models were used to evaluate the association between the types of bacterial species isolated, number of previous surgeries, and severity of neo-osteogenesis.Thirty of the 90 (33.3%) patients had radiologic evidence of neo-osteogenesis. Pseudomonas aeruginosa was significantly associated with neo-osteogenesis (odds ratio [OR], 3.97; 95% confidence interval [CI], 1.12 to 13.56), whereas Staphylococcus aureus was not. The number of previous surgeries, especially 2 or more previous surgeries, was associated with the extent of neo-osteogenesis (OR, 3.48; 95% CI, 1.14 to 10.51). The LMS was also significantly associated with the extent of neo-osteogenesis.The presence of P. aeruginosa in the sinuses is an independent predictor of neo-osteogenesis, whereas S. aureus is not. The number of previous surgeries and the LMS are also independently associated with the severity of neo-osteogenesis.
View details for DOI 10.1002/alr.21485
View details for PubMedID 25644047
Consistent ipsilateral development of the posterior extension of the quadrangular cartilage and bony spur formation in nasal septal deviation.
Otolaryngology--head and neck surgery : official journal of American Academy of Otolaryngology-Head and Neck Surgery
2015; 152 (3): 444-448
Septal spurs are exceedingly common structural deformities that contribute to nasal obstruction and often require surgical correction. The posterior extension of the quadrangular cartilage (PEQC) and its relationship with septal spurs have not been previously examined. We seek to examine the anatomic and histologic relationship of the PEQC and concurrent septal spurs in patients undergoing septoplasty.Prospective cohort study.Facial plastic and rhinology center in tertiary hospital setting.Thirty patients with septal deviation are described in this series. The quadrangular cartilage and associated septal spur were removed en bloc from patients undergoing septoplasty. The length of the PEQC, the side of spur deviation, and the relationship of the PEQC to the spur (ipsilateral vs contralateral) were recorded.The mean length of the PEQC, beyond the bony-cartilaginous junction, was 30.06 ± 6.06 mm. The PEQC was present on the ipsilateral side of the spur deviation in all 30 patients (100%).At sites of septal spur formation, the quadrangular cartilage possesses an average 3-cm extension beyond its junction with the bony components of the septum. This cartilaginous extension is exclusively found on the same side of spur deviation. These findings have implications on our understanding of the ontogeny of commonly found septal spurs and deviations, as well as treatment strategies and cartilage graft harvesting.
View details for DOI 10.1177/0194599814564549
View details for PubMedID 25573678
Inverted Papilloma of the Sphenoid Sinus: Risk Factors for Disease Recurrence
2015; 125 (3): 544-548
Surgical treatment of inverted papilloma (IP) of the sphenoid sinus is complicated by close proximity to vital structures of the skull base. Identifying the site of tumor attachment and achieving complete removal can be challenging compared to IP at other sites. The objective of this study is to illustrate the clinical presentation, management, and risk factors for tumor recurrence for sphenoid IP.Retrospective study.A multi-institutional, retrospective review of endoscopic resections of IP based within the sphenoid sinus was performed from 1996 to 2014. Demographic and tumor data, operative notes, complications, and recurrence rates were collected. Statistical analysis was performed to identify risk factors for tumor recurrence.Forty-eight patients (31 males, 17 females) were identified. Mean age was 57 years, with a median follow-up of 13.6 months (range 6.8-36). Rate of tumor recurrence was 14.6%, with median time to recurrence of 13.1 months. Patients with dysplasia/carcinoma in situ (CIS) had a 3.6 greater rate of recurrence (RR) compared to patients with no dysplasia, approaching significance (RR = 3.6; P = 0.08). Patients with IP attachment sites overlying the optic nerve or carotid artery had a 4.76 greater rate of recurrence compared to other sites (RR = 4.76; P = 0.073).Sphenoid sinus IP is associated with a 14.6% rate of recurrence after surgery. Potential risk factors for tumor recurrence identified in this study include attachment sites over the optic nerve and carotid artery or evidence of dysplasia or CIS. Close follow-up in the postoperative period is essential for these patients to monitor for tumor recurrence.
View details for DOI 10.1002/lary.24929
View details for Web of Science ID 000349964100014
View details for PubMedID 25418985
Complications associated with the pedicled nasoseptal flap for skull base reconstruction.
2015; 125 (1): 80-85
To analyze complications associated with nasoseptal flap elevation and reconstruction in endoscopic skull base surgery.Case series.Retrospective chart review of all patients who underwent nasoseptal flap procedure in our institution between 2008 and 2013.A total of 121 patients were identified with a mean follow-up time of 10.4 months. Complications associated with this procedure occurred in 33 patients (27%). The majority of complications were related to the septal donor site and included septal perforation, cartilage necrosis, and prolonged crusting. Other complications included intraoperative injury to the flap pedicle (n = 4) or recurrent/persistent cerebrospinal fluid leak occurring in the early postoperative period (n = 7). Long-term quality-of-life data assessed via Sinonasal Outcome Test-22 questionnaires did not reveal notable differences when compared to preoperative scores.The complication rate associated with nasoseptal flap elevation and inset is higher than previously described. The majority of complications became manifest beyond the immediate postoperative period and were associated with the septal donor site, including septal perforation, prolonged crusting, and cartilage necrosis. We hypothesize that donor site morbidity may be related to compromise of the contralateral septal vascular supply during the procedure. The range and frequency of complications of nasal septal flap surgery should be considered in counseling patients who may receive a nasoseptal flap for skull base reconstruction.4. Laryngoscope, 125:80-85, 2015.
View details for DOI 10.1002/lary.24863
View details for PubMedID 25111727
- Long-term outcomes of endoscopic maxillary mega-antrostomy for refractory chronic maxillary sinusitis. International forum of allergy & rhinology 2015; 5 (1): 60-65
The Combined Subtemporal-Transfacial Approach for the Resection of Juvenile Nasopharyngeal Angiofibromas With Intracranial Extension
OTOLOGY & NEUROTOLOGY
2015; 36 (1): 151-155
Stage IVb juvenile nasopharyngeal angiofibromas (JNAs) are frequently regarded as unresectable because of their intracranial extension and cavernous sinus invasion. Although radiation has been described to control these tumors, it can leave the adolescent with long-lasting sequelae. Herein, we describe an alternative treatment strategy based on a combined subtemporal-transfacial surgical approach that permits the successful management of advanced stage JNAs by divorcing the intracranial vascular supply to these massive lesions.Four male patients were identified with Andrew's Stage IVB JNAs.All patients were treated by surgical resection using a combined subtemporal-transfacial surgical approach.Parameters assessed included tumor extent, number and types of surgical procedures, extent of resections, complications, and recurrence rate.Near-total tumor resections were achieved in all patients. No cerebrospinal fluid leak or cranial neuropathies were noted. All but one patient had local recurrences, and these could be managed with repetitive endoscopic debridement. No patient required adjuvant radiation treatment to control advanced disease.With the use of modern skull base surgical techniques, coordinated interdisciplinary care, and safe, near-total removal of the tumor mass, adolescent males with advanced JNAs may be spared the long-term morbidities associated with using radiation to treat these benign but aggressive lesions.
View details for Web of Science ID 000346368200030
View details for PubMedID 25036780
Air pollutants cause release of hydrogen peroxide and interleukin-8 in a human primary nasal tissue culture model.
International forum of allergy & rhinology
2014; 4 (12): 966-971
A component of primary innate defense of the nasal mucosa against inhaled pathogens includes continuous, low-level release of hydrogen peroxide (H2 O2 ) into luminal secretions. Epidemiologically, an association exists between poor air quality and increased prevalence of sinonasal disease. To understand the effects of particulate matter (PM) in nasal mucosa, we studied the release of H2 O2 and interleukin 8 (IL-8) after PM exposure.Human nasal specimens were collected from surgery and cultured in serum-free growth medium. Cell integrity and recovery during culture was monitored by lactate dehydrogenase (LDH) release into the medium. Cultures were exposed to PM for 24 hours in the presence/absence of diphenyleneiodonium sulfate (DPI; a nicotinamide adenine dinucleotide phosphate [NADPH] oxidase inhibitor). Luminex cytokine and Amplex-Red H2 O2 assays were performed.LDH levels dropped rapidly within 2 days, indicative of stabilization and cell recovery after harvest. All cultures released H2 O2 into the medium. Exposure to PM (20 μg/cm(2) ) increased H2 O2 levels significantly (94.6 ± 7.7 nM) compared to untreated controls (55.8 ± 4.0 nM; p = 0.001). PM-induced H2 O2 production was partially inhibited by DPI (80.1 ± 3.8nM), indicating that cellular NADPH oxidase may be a primary source of H2 O2 production. Exposure to PM increased IL-8 levels in a dose-dependent fashion (control = 2301 ± 412 MFI; 20 μg/cm(2) = 5002 ± 1327 MFI; 40 μg/cm(2) = 8219 ± 1090 MFI; p = 0.022).PM increases the quantity of H2 O2 released by nasal epithelial cells, indicating that PM can contribute to oxidative stress in part by activating a normal cellular defense mechanism. Exposure to PM resulted in elevated IL-8 levels and mucin production in explants. Efforts to reduce airborne PM may lead to reduced H2 O2 and mucin production in sinonasal epithelium.
View details for DOI 10.1002/alr.21413
View details for PubMedID 25400124
A case of stereotactic radiation in skull base solitary fibrous tumor: more harm than good?
Journal of neurological surgery reports
2014; 75 (2): e214-6
Objective Due to its location, total resection of a skull base solitary fibrous tumor (SFT) can lead to morbidity with injury to lower cranial nerves, and a decision must be made between subtotal resection with possible stereotactic radiotherapy or total resection with cranial nerve morbidity. We report the long-term outcomes and review the literature of a case of stereotactic radiation in SFT to provide evidence for making this decision. Design A retrospective case review. Setting An academic tertiary referral center. Results We present a case with > 10 years follow-up of radiation following skull base SFT, initially misdiagnosed as schwannoma, where radiotherapy did not improve recurrence or metastatic behavior and led to complications during subsequent surgical resection. Conclusions SFT often masquerades as schwannoma, especially in the skull base. Careful immunohistochemistry, including CD34 expression, is critical to the diagnosis and management. This case highlights that total tumor resection of SFT remains the gold standard of treatment. Stereotactic radiation is not recommended in the management of skull base SFT.
View details for DOI 10.1055/s-0034-1387196
View details for PubMedID 25485216
View details for PubMedCentralID PMC4242816
- Long-term Sinonasal Outcomes of Aspirin Desensitization in Aspirin Exacerbated Respiratory Disease OTOLARYNGOLOGY-HEAD AND NECK SURGERY 2014; 151 (4): 575-581
Anatomic relationship of nasolacrimal duct and major lateral wall landmarks: cadaveric study with surgical implications
INTERNATIONAL FORUM OF ALLERGY & RHINOLOGY
2014; 4 (8): 684-688
Detailed knowledge of the surgical anatomic landmarks of the lateral nasal wall is important for safe and successful endoscopic sinonasal surgery. We sought to determine the relationship of major landmarks to the nasolacrimal duct (NLD).Twenty mid-sagittal head sections of 10 fresh frozen cadavers were studied after removal of the nasal septum. The insertion of the alar cartilage into the maxilla was taken as a fixed point and all measurements were performed in a defined axial plane at the level of the maxillary sinus natural ostium. Two surgeons independently recorded each measurement 3 times with an average of the readings used for statistical analysis.The overall agreement index was excellent (r = 0.84) between the observers. At the level of maxillary ostium, the mean distance from the alar rim to the NLD was 43.05 ± 4.76 mm on the right and 41.25 ± 4.56 mm on the left. The most anterior projection of the middle turbinate head was noted to be anterior to the NLD in 70% of specimens. In positional relationship, the maxillary line was posterior to the NLD in 55%, whereas the bulla ethmoidalis and the free edge of uncinate process were uniformly posterior to the NLD in all the specimens.This study provides useful anatomic and positional relationships between the NLD and major lateral wall landmarks. Although the maxillary line and the head of the middle turbinate are often considered useful guides to the position of the ipsilateral NLD, their spatial relationship to the NLD is not consistent. These landmarks, therefore, cannot be solely relied upon during surgery to avoid injury to the NLD.
View details for DOI 10.1002/alr.21345
View details for Web of Science ID 000340415400014
View details for PubMedID 24845875
Outpatient endoscopic sinus surgery in cystic fibrosis patients: predictive factors for admission.
International forum of allergy & rhinology
2014; 4 (5): 416-421
An increasing number of adult patients with cystic fibrosis (CF) are becoming candidates for elective endoscopic sinus surgery (ESS). We sought to identify perioperative factors in this patient population that were predictive of postoperative admission.Retrospective chart review of CF patients who underwent ESS during the years 2005 through 2012. Multiple preoperative, intraoperative, and immediate postoperative variables were analyzed.Thirty-three patients who underwent 37 outpatient ESSs were identified. Successful same-day discharge was observed in 54%. In 46% of cases, postoperative admission was necessary, with a mean postoperative stay of 1.4 days. Pulmonary function, CF-related comorbidities, and history of lung transplant were not predictors of postoperative admission. Univariate analysis demonstrated that patients were more likely to be admitted if they had 1 of the following conditions: history of ≥4 prior ESS; procedure duration >2.5 hours; intraoperative blood loss greater than 150 mL; increased immediate postoperative pain scores; or larger narcotic requirements for pain control. On logistic regression analysis, a maximum pain score ≥ 7 out of 10 in the postanesthesia recovery unit was the only significant predisposing factor for postoperative admission.Although over 50% of adult CF patients can successfully undergo ESS on a same-day discharge basis, it is prudent to have contingent plans for potential inpatient observation postoperatively. Multivariate analysis suggests that preoperative demographics and pulmonary status cannot predict the need for postoperative admission, whereas higher pain scores in the postanesthesia care unit are predictive of the necessity for inpatient observation.
View details for DOI 10.1002/alr.21285
View details for PubMedID 24431198
Endoscopic reconstruction of surgically created skull base defects: a systematic review.
Otolaryngology--head and neck surgery : official journal of American Academy of Otolaryngology-Head and Neck Surgery
2014; 150 (5): 730-738
To systematically review the literature concerning techniques of closure of endoscopically created skull base defects based on site of skull base defect and flow rate of cerebrospinal fluid (CSF).PubMed, SCOPUS, and Cochrane databases.A comprehensive systematic literature review.The literature search produced a total of 1708 studies. Of these, 1585 studies were excluded based on title and/or abstract review. A total of 123 articles remained for full-text review, 101 of which were subsequently excluded primarily because of lack of detailed information as to the reconstructive techniques used or clinical outcomes. Of the 22 studies remaining for final analysis, all were case series. A total of 673 patients were included in the analysis, with an overall postoperative CSF leak rate of 8.5%. Subgroup analysis was performed based on location of the skull base defect and presence and quality of intraoperative CSF leak.Based on level 4 evidence, in cases of low-flow intraoperative CSF leaks, skull base reconstruction with multilayered free grafts and synthetic materials offers similar outcomes to vascularized flaps. In cases of high-flow intraoperative CSF leaks, pedicled vascularized flaps appear to be superior. Location of the defect does not seem to be a significant factor in determining successful closure, with the exception of clival defects. In all other sites, good closure may be achieved by multiple reconstructive approaches. More consistency in data reporting and higher levels of evidence will ultimately be necessary to make definitive recommendations.
View details for DOI 10.1177/0194599814520685
View details for PubMedID 24493791
Experience with intraoperative navigation and imaging during endoscopic transnasal spinal approaches to the foramen magnum and odontoid.
2014; 36 (3): E4-?
Object In this study the authors share their experience using intraoperative spinal navigation and imaging for endoscopic transnasal approaches to the odontoid in 5 patients undergoing C1-2 surgery for basilar invagination at Stanford Hospital and Clinics from 2010 to 2013. Methods Of these 5 patients undergoing C1-2 surgery for basilar invagination, 4 underwent a 2-tiered anterior C1-2 resection with posterior occipitocervical fusion during a first stage surgery, followed by endoscopic endonasal odontoidectomy in a separate setting. Intraoperative stereotactic navigation was performed using a surgical navigation system in all cases. Navigation accuracy, characterized as target registration error, ranged between 0.8 mm and 2 mm, with an average of 1.2 mm. Intraoperative imaging using a CT scanner was also performed in 2 patients. Results Endoscopic decompression of the brainstem was achieved in all patients, and no intraoperative complications were encountered. All patients were extubated within 24 hours after surgery and were able to swallow within 48 hours. After appropriate initial reconstruction of the defect at the craniocervical junction, no postoperative CSF leakage, arterial injury, or need for reoperation was encountered; 1 patient developed mild postoperative velopharyngeal insufficiency that resolved by the 6-month follow-up evaluation. There were no deaths and no patients required tracheostomy placement. The average inpatient stay after surgery varied between 72 and 96 hours, without extended intensive care unit stays for any patient. Conclusions Technologies such as intraoperative CT scanning and merged MRI/CT can provide the surgeon with detailed, virtual real-time information about the extent of complex endoscopic vertebral segment resection and brainstem decompression and lessens the prospect of revision or secondary procedures in this challenging surgical corridor. Moreover, patients experience limited morbidity and can tolerate early oral intake after transnasal endoscopic odontoidectomy. Essential to the successful undertaking of these endoscopic adventures is 1) an understanding of the endoscopic nasal, skull base, and neurovascular anatomy; 2) advanced and extended-length instrumentation including navigation; and 3) a team approach between experienced rhinologists and spine surgeons comfortable with endoscopic skull base techniques.
View details for DOI 10.3171/2014.1.FOCUS13533
View details for PubMedID 24580005
- Human ethmoid sinus mucosa: a promising novel tissue source of mesenchymal progenitor cells STEM CELL RESEARCH & THERAPY 2014; 5
Systemic prednisone administration selectively alters granulocyte subsets in nasal polyps from aspirin-exacerbated respiratory disease and chronic rhinosinusitis patients.
International forum of allergy & rhinology
2013; 3 (11): 866-876
Nasal polyps (NPs) are hallmark inflammatory lesions of sinusitis. Despite the spectrum of NP conditions, cellular differences between NPs from patients with chronic rhinosinusitis with NPs (CRSwNP) and aspirin-exacerbated respiratory disease (AERD) are poorly understood. NPs are associated with abundant eosinophils; the contributions of neutrophil and basophil granulocytes are less defined. We therefore sought to assess granulocyte subpopulations, and differential effects following prednisone pretreatment, within NPs of CRSwNP and AERD patients.NPs, adjacent ethmoid sinus tissue, and peripheral blood mononuclear cells (PBMCs) were obtained from patients undergoing endoscopic sinus surgery. Samples from 5 cohorts: CRSwNP ± prednisone (n = 6 each), AERD ± prednisone (n = 6 each), and controls (n = 9), were analyzed by high-dimensional flow cytometry to gate granulocyte populations. Specimens were also assessed using immunohistochemistry (IHC) staining.Systemic prednisone administration was associated with a lower frequency of eosinophils (p < 0.0001, n = 6) in NPs in both CRSwNP and AERD patients, whereas a decrease in neutrophils (p = 0.0070, n = 6) in NPs was only observed in CRSwNP patients after prednisone treatment. In contrast, steroids do not alter basophil proportions (p = 0.48, n = 6) within NPs from either group. No significant shift in granulocyte subsets after steroid treatment was identified in the adjacent ethmoid mucosa or PBMCs from the same patients. Immunohistochemistry (IHC) staining supported these findings.Granulocyte subpopulations are focally affected within NPs by systemic steroid exposure, without notable granulocyte alterations in the surrounding regional tissues. These data provide direct insights into the cellular effects of routine prednisone exposure in CRS patients, and highlight a unique microenvironment present within NP lesions.
View details for DOI 10.1002/alr.21221
View details for PubMedID 24106221
Characterization of human upper airway epithelial progenitors.
International forum of allergy & rhinology
2013; 3 (10): 841-847
New epithelial cells are generated through the proliferation and differentiation of resident progenitor cells in the nasal cavity. In several upper airway diseases, such as cystic fibrosis and chronic rhinosinusitis, self-renewing progenitor cells may be functionally defective, or compromised in their ability, to regenerate cells that maintain normal mucociliary clearance. Herein, we describe our early work to define and characterize a rare population of human nasal epithelial putative progenitors.Single-cell suspensions of human ethmoid sinus tissues were prepared following endoscopic sinus surgery. Cell surface antibodies were analyzed as candidate markers for detecting progenitor cells. A panel of antibodies, including epithelial cell adhesion molecule (EpCAM, epithelial cells), CD45 (hematopoietic cells), nerve growth factor receptor (NGFR/CD271), intercellular adhesion molecule-1 (ICAM1/CD54), and integrin-α6 (ITGA6/CD49f) were used to resolve epithelial progenitor candidates by high-dimensional flow cytometry and the gating technique of fluorescence minus one (FMO) controls.A rare population of approximately 0.06% of total ethmoid cells was discriminated as EpCAM(-) CD45(-) NGFR(+) ICAM1(+) by surface markers. Use of ITGA6 was excluded based on FMO control analysis. This lineage-negative population was purified to 99% homogeneity by cell sorting and analyzed by immunofluorescence microscopy. Sorted cells were subsequently confirmed to uniformly express the transcription factor p63. Upon in vitro culture, lineage-negative clonal cells were confirmed to spontaneously differentiate into epithelial lineage-positive cells.Using the NGFR and ICAM1 cellular coordinates, we have identified a promising population of native human nasal epithelial progenitor cells that require more formal investigation for their role in upper airway regeneration.
View details for DOI 10.1002/alr.21205
View details for PubMedID 23901007
Expression of dual oxidases and secreted cytokines in chronic rhinosinusitis.
International forum of allergy & rhinology
2013; 3 (5): 376-383
The airway epithelium generates reactive oxygen species (ROS) as a first line of defense. Dual oxidases (DUOX1 and DUOX2) are the H2 O2 -producing isoforms of the nicotinamide adenine dinucleotide phosphate (NADPH) oxidase family in the airway epithelium. The purpose of this study was to explore the molecular expression, function, and regulation of DUOXs in chronic rhinosinusitis (CRS).Human nasal tissue samples and nasal secretions were collected from 3 groups of patients undergoing sinus surgery (normal, n = 7; CRS with polyposis [CRSwP], n = 6; CRS without polyposis [CRSsP], n = 6). Nasal secretions were studied for cytokine and H2 O2 content. Tissue samples were used to determine DUOX mRNA and protein expression.DUOX1 mRNA level (80.7 ± 60.5) was significantly increased in CRSwP compared to normal (2.7 ± 1.2) and CRSsP (2.3 ± 0.5, p = 0.042). DUOX2 mRNA levels were increased in both CRSwP (18.6 ± 9.9) and CRSsP (4.0 ± 1.3) compared to normal (1.1 ± 0.3; p = 0.008). DUOX protein was found in the apical portion of the nasal epithelium and protein expression was increased in CRSwP and CRSsP. H2 O2 production was significantly higher in CRSwP (160.9 ± 59.4 nM) and CRSsP (81.7 ± 5.6 nM) compared to normal (53.5 ± 11.5 nM, p = 0.032). H2 O2 content of nasal secretions correlated tightly with DUOX expression (p < 0.001). Cytokines (eotaxin, monokine-induced by interferon γ [MIG], tumor necrosis factor [TNF]-α, interleukin [IL]-8) showed significantly higher levels in nasal secretions from CRSwP compared to normal (p < 0.05). Levels of eotaxin, MIG, and TNF-α correlated closely with DUOX expression.DUOX1 and DUOX2 were identified as factors upregulated in CRS. Close correlations between DUOX expression and H2 O2 release, and correlation between key inflammatory cytokines and DUOX expression, indicate DUOX in the inflammatory response in CRS.
View details for DOI 10.1002/alr.21133
View details for PubMedID 23281318
Survival outcomes in acute invasive fungal sinusitis: A systematic review and quantitative synthesis of published evidence.
2013; 123 (5): 1112-1118
Acute invasive fungal sinusitis (AIFS) is an aggressive and often fatal infection. Despite improvements in medical and surgical therapy, survival remains limited and the factors that contribute to patient outcomes remain poorly understood. The current study systematically reviews and quantitatively synthesizes the published literature to characterize prognostic factors associated with survival.Systematic review.Fifty-two studies comprising a total of 807 patients met inclusion criteria and were used for analysis of treatment, presentation, and outcomes. Univariate and multivariate logistic regression was used to identify prognostic factors.All studies were classified as level 4 evidence, as per definitions provided by the Oxford Center for Evidence-Based Medicine. The most common presenting symptoms of patients with AIFS were facial swelling (64.5%), fever (62.9%), and nasal congestion (52.2%). Most patients were treated with a combination of intravenous antifungal medication and surgery. The overall survival rate was 49.7%. On univariate analysis, poor prognosis was associated with renal/liver failure, altered mental status, and intracranial extension. Patients who were diabetic, had surgery, or received liposomal amphotericin B had an improved chance of survival. On multivariate analysis, advanced age and intracranial involvement were identified as independent negative prognostic factors. Positive prognostic factors again included diabetes and surgical resection.The overall mortality of patients with AIFS remains high, with only half of the patients surviving. Diabetic patients appear to have a better overall survival than patients with other comorbidities. Patients who have intracranial involvement, or who do not receive surgery as part of their therapy, have a poor prognosis.N/A.
View details for DOI 10.1002/lary.23912
View details for PubMedID 23300010
Trends in incidence and susceptibility among methicillin-resistant Staphylococcus aureus isolated from intranasal cultures associated with rhinosinusitis.
American journal of rhinology & allergy
2013; 27 (2): 134-137
Reports regarding the incidence and antibiotic susceptibility of methicillin-resistant Staphylococcus aureus (MRSA) in rhinosinusitis (RS) are limited. This study was designed to identify epidemiology and trends of MRSA incidence and antimicrobial resistance in the sinonasal cavities.This is a retrospective case series. All intranasal/sinus cultures obtained by otolaryngologists at Stanford over a 20-year period (1990-2010) were retrospectively reviewed by mining the microbiology database. Nested searches were then made for all S. aureus and MRSA cultures. Patterns of incidence and changes in antibiotic susceptibilities were tabulated and statistical analysis was performed.Our search retrieved 10,387 positive intranasal culture samples, with S. aureus found in 800 (7.7%), and MRSA comprising 110 (1.06%) of this subset. Between the years of 1990 and 1999, only 2/112 (1.7%) of S. aureus-positive nasal cultures were positive for MRSA, with a sharp rise in incidence to 86/606 (14.2%) from 2000 to 2005, and to 22/82, 26.8% from 2006 to 2010. On a percent basis, using logistic regression modeling, this represents a statistically significant increasing trend (p < 0.0001) for MRSA sinusitis. However, over the 20-year interval studied, the patterns of antibiotic resistance among MRSA remained unaltered, especially with regard to trimethoprim-sulfamethoxazole and vancomycin.S. aureus and MRSA isolates from intranasal cultures, which were essentially absent before the year 2000, became significantly more common earlier this decade. These data show the increased role of MRSA in sinusitis. MRSA antibiotic susceptibilities have remained, however, largely stable during this time period.
View details for DOI 10.2500/ajra.2013.27.3858
View details for PubMedID 23562203
Low-frequency pulsed ultrasound in the nasal cavity and paranasal sinuses: a feasibility and distribution study
INTERNATIONAL FORUM OF ALLERGY & RHINOLOGY
2012; 2 (4): 303-308
Bacterial biofilms have been implicated in refractory rhinosinusitis. Biofilms have been shown to respond to treatment with low-frequency ultrasound (LFU) therapy in vitro, and exposure to LFU has shown efficacy in wound repair and topical drug delivery in other fields. This preliminary study was designed to evaluate the safety and feasibility of LFU for use in the nasal cavity and paranasal sinuses.This was an experimental observational study. Six cadaver heads were used to deliver a mixture of Renografin and methylene blue solvent to the paranasal sinuses via LFU both before and after resident endoscopic sinus dissection. Sinus computed tomography (CT) scans of the cadaver heads were performed before and after mixture delivery, and blinded assessments were made for distribution to individual sinuses. Mucosa was harvested from 2 subsites to evaluate LFU-treated cadaver tissue.Predissection, LFU delivered solution to 12 of 12 inferior and middle turbinates, 6 of 12 of the superior turbinates and ethmoid sinuses, and 1 of 12 maxillary sinuses as shown by contrast radiography. Postdissection, all heads showed delivery to the maxillary and sphenoid sinuses, with 8 of 12 sinus cavities showing delivery to the ethmoid region, and 4 of 11 to the frontal recess. Using hematoxylin and eosin (H&E) staining of tissue frozen sections, harvested tissue demonstrated no architectural damage to the mucosal layer from LFU exposure.LFU appears to be capable of reliably delivering topical solution to the turbinates and ethmoid region preoperatively and to all sinuses, except the frontal, postoperatively. The nasal epithelium does not appear to be disrupted histologically from LFU at this time and distance. This data provides a foundation for a prospective human protocol studying the efficacy of this modality in the treatment of patients with chronic rhinosinusitis and biofilm formation.
View details for DOI 10.1002/alr.21039
View details for Web of Science ID 000308927400007
View details for PubMedID 22528624
Nationwide incidence of major complications in endoscopic sinus surgery
INTERNATIONAL FORUM OF ALLERGY & RHINOLOGY
2012; 2 (1): 34-39
Endoscopic sinus surgery (ESS) is one of the most commonly performed procedures in otolaryngology. Major complications are estimated to occur in 1-3% of cases, based on early studies with relatively small patient cohorts in academic institutions. The aim of this study was to update data regarding major complication rates associated with ESS by analyzing a large patient database.Retrospective review of a nationwide database of patients who underwent ESS between 2003 and 2007. Major postoperative complications-cerebrospinal fluid (CSF) leak, orbital injury, and hemorrhage requiring blood transfusion-were identified by searching the database for related International Classification of Diseases, 9th edition (ICD-9) and Current Procedural Terminology (CPT) codes. Complication rates were examined and time to occurrence analyzed. Two-tailed test of proportions, global chi-square test, and logistical regression analysis were used for statistical comparison.A total of 62,823 patients who met rigorous inclusion criteria were included. The overall major complication rate was 1.00% (CSF leak 0.17%; orbital injury 0.07%; hemorrhage requiring transfusion 0.76%). CSF leak was less likely to occur in the pediatric population (p = 0.05), whereas orbital injury was more likely to occur in children (p < 0.001). Examination of the impact of image guidance (IGS) was limited by study design.The incidence of major complications associated with ESS appears to have decreased since early reports over 10 years ago. There may be different complication rates in the pediatric population. Study design limitations did not allow for comprehensive assessment of IGS in the development of these complications. These data help to educate otolaryngologists and patients about complication rates in ESS in a modern context.
View details for DOI 10.1002/alr.20101
View details for Web of Science ID 000308925100007
View details for PubMedID 22311839
- Sinonasal seromucinous hamartomas: Clinical features and diagnostic dilemma OTOLARYNGOLOGY-HEAD AND NECK SURGERY 2010; 143 (1): 165-166
Assessing the risk of irrigation bottle and fluid contamination after endoscopic sinus surgery
55th Annual Meeting of the American-Rhinologic-Society
OCEAN SIDE PUBLICATIONS INC. 2010: 197–99
Saline nasal irrigation has become an important aspect of post-operative care following endoscopic sinus surgery. The objective of this study was to identify the risks of contamination of both the nasal irrigation bottle and fluid following endoscopic sinus surgery.This was a prospective study of consecutive patients undergoing endoscopic sinus surgery for chronic sinusitis. All patients were given nasal irrigation bottles with detailed cleaning instructions preoperatively. Nasal irrigation bottles were collected and cultured at 1 and 2 weeks postoperatively. During the same visit, 5-ml of sterile normal saline was mixed into the irrigation bottle and then cultured separately.A total of 20 patients agreed to participate in the study. At 1 week postoperatively, 50% of the bottles had positive cultures with 40% of the irrigation samples testing positive for bacteria. At two weeks, the contamination in the irrigation bottle and fluid decreased to 26.7% and 20%, respectively. The most common bacteria cultured was Pseudomonas aeruginosa. There were no cases of postoperative infection.Despite detailed cleaning instructions, there is a relatively high risk of bacterial contamination in nasal irrigation bottles and fluid following endoscopic sinus surgery. Although these risks did not translate into higher infection rates postsurgery, it may be important for physicians to emphasize regular cleaning techniques to minimize a potential source of bacterial contaminant exposure.
View details for DOI 10.2500/ajra.2010.24.3481
View details for Web of Science ID 000278843200007
View details for PubMedID 20537286
Biofilms in chronic rhinosinusitis: A review
AMERICAN JOURNAL OF RHINOLOGY & ALLERGY
2009; 23 (3): 255-260
Bacterial biofilms consist of a complex, organized community of bacteria that anchor to both biotic and abiotic surfaces. They are composed of layers of embedded, live bacteria within extruded exopolymeric matrix. This configuration allows for evasion of host defenses and decreased susceptibility to antibiotic therapy while maintaining the ability to deliberately release planktonic bacteria, resulting in recurrent acute infections. Thus, bacterial biofilms were hypothesized to contribute to the progression and persistence of chronic rhinosinusitis.This review summarizes several of the seminal papers supporting this hypothesis.Multiple reports using various imaging modalities have demonstrated the presence of biofilms in sinonasal mucosa of patients with chronic rhinosinusitis. More recently, several studies have correlated the presence of biofilms with poor clinical outcomes in the disease process. Early therapeutic interventions have generated mixed results.Bacterial biofilms appear to contribute to the progression of chronic rhinosinusitis in a subset of patients, although substantial effort toward therapeutic intervention is still necessary.
View details for DOI 10.2500/ajra.2009.23.3319
View details for Web of Science ID 000266387300004
View details for PubMedID 19490797
Head and neck epithelioid sarcoma in a child: Diagnostic dilemma and anterolateral thigh free flap reconstruction
INTERNATIONAL JOURNAL OF PEDIATRIC OTORHINOLARYNGOLOGY
2008; 72 (5): 719-724
The diagnostic dilemma is discussed of a child who presented with a granulomatous process of the external ear that was originally considered granuloma annulare and was later diagnosed as epithelioid sarcoma. We present the surgical treatment and the first report of reconstruction of a lateral skull base and cheek defect with an anterolateral thigh (ALT) free flap in a pediatric patient.
View details for DOI 10.1016/j.ijport.2008.01.032
View details for Web of Science ID 000255321200028
View details for PubMedID 18346795
Head and Neck Cancer Immunotherapy: Clinical Evaluation
CURRENT ONCOLOGY REPORTS
2008; 10 (2): 162-169
Overall survival for patients with squamous cell carcinoma of the head and neck (SCCHN) has not improved appreciably over the past few decades. Because standard treatments have not controlled this disease with sufficiently high success rates, novel therapeutic approaches, such as immunotherapy, are under investigation. Cancer immunotherapy involves various techniques used to expand and activate the immune system to control tumor growth in vivo; to date, clinical evaluation has demonstrated low toxicity. An emerging form of SCCHN immunotherapy involves the use of antibodies that target growth factor receptors (where immune activation appears to enhance tumor lysis), resulting in improved clinical outcome. So far, immunotherapy appears to have the most applicability after other therapeutic interventions; however, its vast potential clinical value has yet to be fully explored. This article reviews immunotherapeutic strategies currently in clinical trials or under development for patients with SCCHN.
View details for Web of Science ID 000207842200011
View details for PubMedID 18377830
Deferring planned neck dissection following chemoradiation for stage IV head and neck cancer: The utility of PET-CT
110th Annual Meeting of the Triological-Society
WILEY-BLACKWELL. 2007: 2129–34
To determine whether combined positron emission tomography and computed tomography (PET-CT) may be of value in deferring planned neck dissections for patients with advanced head and neck squamous cell carcinoma (HNSCC).Observational study of patients with de novo cervical > or =N2 regional spread of HNSCC in a tertiary care academic medical center.Forty-three patients were identified who underwent post-treatment PET-CT within 6 months of completing neoadjuvant chemotherapy combined with radiation therapy (CRT). The PET-CT was "positive" if the radiologist recommended tissue sampling or resection of cervical lymph nodes, or if there was progressive neck disease in the setting of distant metastatic disease. Patients who had positive PET-CT underwent confirmatory biopsy given clinical suspicion for regional cervical metastasis without distant disease. Patients with negative PET-CT were followed clinically and radiographically for a minimum of 5 months (median 18.1 months) after CRT.Ten (22%) of the 43 post-treatment PET-CT studies were positive. Seven of the 10 PET-CT scans (70% of positives) were true-positive given histologically-confirmed residual viable tumor or progressive disease including disease in the neck. The 3 remaining studies (30% of positives) were false-positive PET-CT results, given resolution of fluorodeoxyglucose (FDG) avidity on subsequent imaging or tissue sampling demonstrating absence of viable tumor cells. Of the 33 patients with negative PET-CTs in the neck, 1 patient had absence of FDG-avidity in the setting of malignant disease in the neck (3% false negatives); otherwise, patients with an initially negative PET-CT scan had no recurrences during the study (97% true negatives). This corresponds to a sensitivity of 87.5% (7/8), a specificity of 91% (32/35), a positive predictive value of 70% (7/10), a negative predictive value of 97% (32/33), and accuracy of 91% (39/43) for PET-CT scans in the detection of cervical metastatic disease after CRT. Overall, 37 (86%) of 43 patients were spared neck dissection using this technology without evidence of recurrent disease in the neck at extended follow-up.Our results suggest that planned neck dissection after CRT for HNSCC may be deferred in favor of serial PET-CT imaging, and that sampling of areas of suspicious FDG-avid uptake can be rationally considered prior to therapeutic neck dissection. These data also suggest that negative PET-CT scans are highly reliable for the absence of residual cervical nodal disease.
View details for DOI 10.1097/MLG.0b013e318149e6be
View details for Web of Science ID 000251397200008
View details for PubMedID 17921898
Experience with the expanded endonasal approach for resection of the odontoid process in rheumatoid disease
52nd Annual Meeting of the American-Rhinologic-Society
OCEAN SIDE PUBLICATIONS INC. 2007: 601–6
One of the common indications for removal of the odontoid process includes decompression of the cervicomedullary junction in patients with arthritic degeneration. Resection of the odontoid process can be accomplished using a completely transnasal endoscopic approach.A retrospective review was performed of patients with rheumatoid pannus undergoing transnasal endoscopic resection of the odontoid to assess preoperative characteristics, postoperative complications, and outcomes. Patients were followed for a minimum of 3 months in the postoperative period and/or until death. In addition to the primary procedure, those patients with preoperative cervical instability underwent posterior fusion of the upper cervical spine to the occiput for stabilization during the same hospitalization.Nine patients underwent transnasal endoscopic resection of the odontoid process for rheumatoid or degenerative pannus and brainstem compression. Perioperatively, four patients required a tracheostomy; two of whom had significant preoperative pharyngeal dysfunction. Two patients experienced postoperative velopharyngeal incompetence, which was transient. No patients had cerebrospinal fluid leaks, and there were no perioperative infectious complications noted. There was one delayed death in this patient cohort because of a presumed pulmonary embolus. Otherwise, all patients showed an improvement of their preoperative neurological symptoms.This early series of patients with rheumatoid pannus shows the feasibility of a fully endoscopic, completely transnasal approach for the resection of the odontoid process. Potential advantages include improved visualization, limited morbidity, decreased pain, and faster recovery than traditional approaches.
View details for Web of Science ID 000250770000015
View details for PubMedID 17999797
Phagocytosis induces lysosome remodeling and regulated presentation of particulate antigens by activated dendritic cells
JOURNAL OF IMMUNOLOGY
2006; 177 (12): 8493-8503
Immunization with particulate Ag effectively induces antitumor and antiviral T cell-mediated immunity. Immature dendritic cells (DCs) efficiently internalize, process, and present a variety of particulate Ags; however, previously published data suggest that both the uptake of soluble Ag through micropinocytosis, and phagocytosis of particulates are significantly curtailed in activated DC populations. In this study, we demonstrate that although macropinocytosis of soluble Ag is diminished following DC activation, subsets of DCs in activated DC populations retain the ability to actively phagocytose particulate Ags. Live cell imaging of activated DCs reveals that phagocytosis of particulates can result in cytoskeletal remodeling and perinuclear lysosome cluster disruption in a time-dependent manner. Interestingly, our results suggest that in activated DC populations, presentation of phagocytosed particulate Ags is dependent on the nature of the activation signal. These results provide direct evidence of functional heterogeneity in DC populations and contribute to the development of particle-based immunization strategies.
View details for Web of Science ID 000243416800026
View details for PubMedID 17142747
Role of antigen-processing machinery in the in vitro resistance of squamous cell carcinoma of the head and neck cells to recognition by CTL
JOURNAL OF IMMUNOLOGY
2006; 176 (6): 3402-3409
Squamous cell carcinoma of the head and neck (SCCHN) cells are poorly recognized in vitro by CTL despite expressing the restricting HLA class I allele and the targeted tumor Ag (TA). Several lines of evidence indicate that the lack of SCCHN cell recognition by CTL reflects defects in targeted TA peptide presentation by HLA class I Ag to CTL because of Ag-processing machinery (APM) dysfunction. First, lack of recognition of SCCHN cells by CTL is associated with marked down-regulation of the IFN-gamma-inducible APM components low-m.w. protein 2, TAP1, TAP2, and tapasin. Second, SCCHN cell recognition by CTL is restored by pulsing cells with exogenous targeted TA peptide. Third, the restoration of CTL recognition following incubation of SCCHN cells with IFN-gamma is associated with a significant (p = 0.001) up-regulation of the APM components TAP1, TAP2, and tapasin. Lastly, and most conclusively, SCCHN cell recognition by CTL is restored by transfection with wild-type TAP1 cDNA. Our findings may explain the association between APM component down-regulation and poor clinical course of the disease in SCCHN. Furthermore, the regulatory nature of the APM defects in SCCHN cells suggests that intralesional administration of IFN-gamma may have a beneficial effect on the clinical course of the disease and on T cell-based immunotherapy of SCCHN by restoring SCCHN cell recognition by CTL.
View details for Web of Science ID 000238768400015
View details for PubMedID 16517708
Current use of F-18-fluorodeoxyglucose positron emission tomography and combined positron emission tomography and computed tomography in squamous cell carcinoma of the head and neck
2005; 115 (11): 2029-2034
The history and physical examination, computed tomography (CT) and magnetic resonance imaging are the cornerstones for identifying new and recurrent cancers of the head and neck. The advent of positron emission tomography (PET) and combined PET/CT imaging technology is a promising development. These modalities have the potential to help stage patients presenting with head and neck cancer, identify responses to nonsurgical therapy, and allow earlier detection of recurrence in the hope of improving survival. The following paper provides a brief history of PET and PET/CT imaging. The current PET and PET/CT literature for squamous cell carcinoma of the head and neck is reviewed, and specific recommendations for its use are provided.
View details for DOI 10.1097/01.MLG.0000181495.94611.A6
View details for Web of Science ID 000233839600023
View details for PubMedID 16319618
Diagnostic utility of positron emission tomography-computed tomography for predicting malignancy in cystic neck masses in adults
2005; 115 (11): 1979-1982
Combined positron emission tomography and computed tomography (PET-CT) is used for the diagnostic evaluation and staging of squamous cell carcinoma of the head and neck (SCCHN). By superimposing anatomic localization of CT with the physiologic data of PET, occult primary and metastatic neoplasms might be identified. Because the diagnostic algorithm for cystic neck masses in adults often overlaps with the work-up of cancer of unknown primary site, we evaluated the utility of PET-CT scans to identify the presence of malignancy and the location of primary tumor.Single-institution retrospective case review series.We reviewed the PET-CT imaging of cystic neck masses occurring in five patients over 40 years of age with significant risk factors for SCCHN and correlated this information with histopathology.In each patient in our series, the PET portion of a combined PET-CT was misleading, whereas the CT examination was more suggestive of the correct pathology. Ultimately, clinical judgment and endoscopic evaluation, guided by CT findings, were most valuable for distinguishing malignant versus benign processes and identifying the primary tumor sites.PET-CT may not be a reliable modality for identifying malignancy in adults with suspicious cystic neck masses. A thorough clinical evaluation by an experienced head and neck surgeon, in conjunction with contrast-enhanced CT, may be sufficient to facilitate the optimal management of such patients.
View details for DOI 10.1097/01.mlg.0000178328.70288.55
View details for Web of Science ID 000233839600014
View details for PubMedID 16319609
Sensitization with xenogeneic tissues alters the heavy chain repertoire of human anti-Ga1 alpha 1-3Ga1 antibodies
2005; 80 (1): 102-109
Antigen sensitization alters the use of genes encoding the variable and constant regions of immunoglobulin, changing avidity, and function. Alterations in variable region genes induced by carbohydrate antigens have been studied extensively in animals but are incompletely characterized in humans. We asked how sensitization with the carbohydrate Galalpha1-3Gal modifies antibody heavy chain use.To overcome limited access to B cells, we analyzed anti-Galalpha1-3Gal antibodies from the serum of naïve and sensitized human subjects with anti-sera specific for VH families.We find that in preimmune subjects, heavy chains of IgM anti-Galalpha1-3Gal derived primarily from VH3 family members, whereas the heavy chains of IgG are from diverse VH families. After sensitization, heavy chains of IgM and IgG antibodies both derived from diverse VH families.The preimmune repertoire of IgM antibodies to Galalpha1-3Gal is thus more restricted than the antibody repertoire after sensitization, suggesting an antigen-induced shift in the repertoire.
View details for DOI 10.1097/01.TP.0000163976.07023.6D
View details for Web of Science ID 000230473800018
View details for PubMedID 16003240
Lipid-protamine-DNA-mediated antigen delivery to antigen-presenting cells results in enhanced anti-tumor immune responses
2003; 7 (5): 640-648
Vaccination with antigenic peptides encoding tumor antigens has the potential to be an effective treatment for cancer. To induce tumor-specific cellular immune responses, a peptide antigen must be presented by antigen-presenting cells (APCs) to T-cells in the lymphatic tissues. Effective in vivo delivery of peptide antigens to APCs has been problematic. Here we use a model antigen from the HPV16 E7 protein to formulate LPD/E7 particles that upon iv administration are internalized by CD11c(+) and CD11b(+) cells in the marginal zone of the spleen. Either iv or sc vaccination with LPD/E7 particles induces E7-specific CTL responses stronger than those obtained using previously described liposome/peptide strategies and prevents the establishment of E7-expressing tumors. Furthermore, the administration of LPD/E7 particles to tumor-bearing mice caused complete tumor regression in 100% of the treated animals. Based on these studies, the entrapment of peptide antigens inside LPD particles may be an effective and generally applicable strategy for the enhancement of peptide vaccine potency.
View details for DOI 10.1016/S1525-0016(03)00064-9
View details for Web of Science ID 000182645800012
View details for PubMedID 12718907
Myoepithelial neoplasia of the submandibular gland - Case report and therapeutic considerations
ARCHIVES OF OTOLARYNGOLOGY-HEAD & NECK SURGERY
2003; 129 (3): 359-362
Tumors of the submandibular gland typically arise from the seromucinous acini, which make up the majority of the gland. The most common benign tumor of this structure is the pleomorphic adenoma, whereas the most common malignancy of the submandibular gland is adenoid cystic carcinoma. We describe an unusual case of a neoplastic process of the myoepithelial cells of the submandibular gland in a middle-aged woman. This rare tumor is most commonly diagnosed in the parotid gland and in the minor salivary glands of the hard palate; a review of the literature uncovered only 5 previous reports of myoepithelioma of the submandibular gland. Distinguishing myoepithelioma from benign pleomorphic adenoma and malignant myoepithelial carcinomas can be challenging. Immunohistochemical staining can help to distinguish between the benign neoplasms, but histologic features remain the "gold standard" for diagnosing the malignant tumors. Increasing use of immunohistochemistry panels to assess parotid neoplasms also suggests that myoepithelioma may be underrecognized.
View details for Web of Science ID 000181522400016
View details for PubMedID 12622550
Primary lymphoma of the larynx: New diagnostic and therapeutic approaches
ORL-JOURNAL FOR OTO-RHINO-LARYNGOLOGY AND ITS RELATED SPECIALTIES
2003; 65 (6): 321-326
Tumors primary in the larynx, when not of squamous cell origin, require special diagnostic and therapeutic attention. An unexpected case of non-Hodgkin's lymphoma localized in the larynx in a patient with a brief history of dysphagia and hoarseness is discussed. This supraglottic tumor was extensively characterized at our institution for morphologic features by microlaryngoscopy, histology, immunocytochemical profiles with flow cytometry, chromosomal aberrations using banded karyotyping and extent of disease via PET-CT imaging. Our detailed analysis distinguished this neoplasm as a new-onset diffuse large B cell laryngeal lymphoma rather than a mucosa-associated lymphoid tissue lymphoma. A rational diagnostic approach guided the combination chemotherapy/immunotherapy treatment strategy instead of traditional localized radiation therapy. These findings highlight the importance of a thorough phenotypic and cytogenetic characterization of head and neck neoplasms, which has implications for downstream diagnostic considerations, interventional strategies and the available therapeutic options. The presence of nonsquamous laryngeal tumors reinforces the dictum to obtain a reliable tissue diagnosis before initiating definitive therapy.
View details for DOI 10.1159/000076049
View details for Web of Science ID 000189170500003
View details for PubMedID 14981324
Intravenous injection of naked DNA encoding secreted flt3 ligand dramatically increases the number of dendritic cells and natural killer cells in vivo
HUMAN GENE THERAPY
2000; 11 (4): 547-554
The trace number of dendritic cells (DCs) present in tissues has limited the study of DC biology and development of clinical applications utilizing DCs. Here we show that hydrodynamics-based gene delivery of naked DNA encoding secreted human flt3 ligand (hFLex) can dramatically increase the number of functional DCs and natural killer (NK) cells. After a single injection of the hFLex gene, hFLex levels in mouse serum reached approximately 40 microg/ml and remained above 1 microg/ml for 5-6 days. Sustained levels of serum hFLex correlated with significant increases in the size of the lymphoid organs and in the proportion of dendritic cells and NK cells in both lymph nodes and spleen. The increase in DC and NK cell numbers started from day 5, and reached peak levels between day 8 and day 12. The levels then returned to normal on day 20. These DCs and NK cells were functional as evidenced by mixed leukocyte reactions and lysis of YAC-1 cells, respectively. These results suggest that delivery of the hFLex gene provides a simple, efficient, and inexpensive way of increasing DC and NK cell populations in vivo, and may have broad applications in the further study of DC and NK cell biology and in the development of immunotherapy strategies.
View details for Web of Science ID 000085659100004
View details for PubMedID 10724033
The dual phases of the response to neonatal exposure to a V-H family-restricted staphylococcal B cell superantigen
JOURNAL OF IMMUNOLOGY
1998; 161 (10): 5720-5732
In vitro studies of several naturally occurring proteins have characterized VH family-specific B lymphocyte binding and stimulatory properties that appear analogous to those of T cell superantigens. To examine the in vivo consequences of exposure to a putative B cell superantigen, we treated neonatal BALB/c mice with a form of staphylococcal protein A (MS) devoid of Fcgamma binding activity, which retains the clan VHIII Fab binding specificity. In naive adults, about 5% of peripheral B cells and >13% of splenic IgM-secreting cells display MS binding activity, in association with high IgM and low IgG circulating anti-MS Ab titers. Neonatal exposure to MS elicited two distinct temporal phases of immune responsiveness. The early phase, representing the first approximately 5 wk of life, was associated with MS-specific B cell and T cell tolerance. Microfluorometric assays revealed that exposure caused a dramatic MS-specific B cell clonal loss in bone marrow and spleen, but levels normalized by about 3 wk of life. The late phase (>6 wk of age) was associated with spontaneous priming for MS-specific T cell responses and production of MS-specific IgG1 Abs despite long term persistently depressed in vivo and in vitro MS-specific IgM responses. In vivo challenge during the late phase induced high frequencies of MS-specific IgG-secreting cells, indicating recruitment of highly focused Ab responses that were predominantly encoded by rearrangements of the S107 family, a member of the VHIII clan. These studies document the immunodominance of the VH-restricted Fab binding site on staphylococcal protein A and demonstrate the diverse effects of a B cell superantigen on the emerging peripheral B cell compartment.
View details for Web of Science ID 000076919100079
View details for PubMedID 9820554
- In vivo consequences of B cell superantigen immunization Conference on B Lymphocytes and Autoimmunity NEW YORK ACAD SCIENCES. 1997: 105–110
B-cell superantigens: molecular and cellular implications.
International reviews of immunology
1997; 14 (4): 259-290
B cell superantigens are proteins that are capable of immunoglobulin variable region mediated binding interactions with the naive B cell repertoire at frequencies that are orders of magnitude greater than occur for conventional antigens. Within this review we discuss recent observations regarding the molecular basis of these interactions and the distribution of superantigen binding capacities in different human B cell populations. These findings and current predictions regarding the relevance of these proteins to the physiologic development of immune repertoires are also discussed.
View details for PubMedID 9186781