- 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
Assistant Professor - Med Center Line, Otolaryngology (Head and Neck Surgery)
Honors & Awards
National Finalist - Clinical Scientist Development Award, Doris Duke Charitable Foundation (December 2014)
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)
Human Mucosal Immune Responses to Influenza Virus: a Systems Biology Approach, NIH/Human Immunology Project Consortium (HIPC) (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)
2D and 3D Electron Microscopy Ultrastructure of Murine Nasal Cavity, Stanford Beckman Center Technology Innovation MiniGrant program (2012)
Influenza virus tropism for human nasal epithelial cells of the upper airway, Marion Avery Family Grant (2012)
CORE Schering Plough Resident Research Award from the American Academy of Otolaryngology, University of Pittsburgh (2005)
Gold Foundation Little Apple Medical Student Teaching Award Finalist, University of Pittsburgh (2004)
Bernhard A. Goldman Prize in Dermatology, University of Pittsburgh (2003)
M.D./Ph.D. Transfer Admission & Full Scholarship Award, University of Pittsburgh (1997)
American Heart Association Medical Student Research Fellowship, U Californioa, San Diego (1996)
Howard Hughes Medical Institute Medical Student Research Fellowship, U California, San Diego (1995)
Stanley J. Sarnoff Endowment Medical Student Research Fellowship, Salk Institute, La Jolla, CA (1994)
Baccalaureate with Honors, University of Pennsylvania (1992)
Co-Valedictorian, Woodbridge High School, New Jersey (1988)
Board Certification: Otolaryngology, American Board of Otolaryngology (2010)
Residency:University of Pittsburgh Medical Center (2008) PA
Internship:University of Pittsburgh Medical Center (2004) PA
Fellowship:University of Pennsylvania (2009) 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)
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
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
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
Long-term outcomes of endoscopic maxillary mega-antrostomy for refractory chronic maxillary sinusitis.
International forum of allergy & rhinology
2015; 5 (1): 60-65
Endoscopic maxillary mega-antrostomy (EMMA) is a revision surgical procedure for recalcitrant maxillary sinusitis in which medical therapy and endoscopic antrostomy have been unsuccessful. In 2008 our group published favorable outcomes of EMMA in 28 patients with relatively short follow-up and nonvalidated outcome measures. This study reports an update of long-term outcomes of this same cohort, as well as outcomes of an interval cohort of 94 patients using validated outcome measures.Retrospective review was performed for 122 patients (163 sides) who underwent EMMA between 2005 and 2013. For the original 2008 cohort, the original questionnaire from 2008 was readministered by telephone interview. For the interval cohort, preoperative and postoperative SNOT-22 symptom scores and modified Lund-Kennedy endoscopic scores were compared.The original 2008 cohort of 28 patients, now with a mean follow-up period of 6.9 years, demonstrated sustained improvement of symptoms. The outcomes were statistically comparable to the 2008 study, with 72.4% reporting complete or significant improvement, 27.6% reporting partial improvement, and 0% reporting worsening.
View details for DOI 10.1002/alr.21407
View details for PubMedID 25312656
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 Web of Science ID 000346022600004
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
- 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
Endoscopic Reconstruction of Surgically Created Skull Base Defects A Systematic Review
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 Web of Science ID 000335572300005
View details for PubMedID 24493791
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
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
- 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
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
- Characterization of human upper airway epithelial progenitors INTERNATIONAL FORUM OF ALLERGY & RHINOLOGY 2013; 3 (10): 841-847
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
- Expression of dual oxidases and secreted cytokines in chronic rhinosinusitis INTERNATIONAL FORUM OF ALLERGY & RHINOLOGY 2013; 3 (5): 376-383
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 Web of Science ID 000320782200011
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
- 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
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
OCEAN SIDE PUBLICATIONS INC. 2010: 197-199
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
2007; 117 (12): 2129-2134
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
AMERICAN JOURNAL OF RHINOLOGY
2007; 21 (5): 601-606
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 B LYMPHOCYTES AND AUTOIMMUNITY 1997; 815: 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