PEARLS AND PITFALLS
| EPISTAXIS: CAUTERY AND PACKING —Jay K. Roberts, MD, Department of Otolaryngology, Cleveland Clinic Florida,
Naples
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| Presentation: patients use variety of methods in attempt to control bleeding (usually self-limited); medical attention often
sought after multiple episodes of epistaxis; medications (eg, aspirin, vitamin E, warfarin [Coumadin], clopidogrel
[Plavix]) may aggravate problem, but control normally achieved without interrupting medical treatment; bleeding originates
from anterior aspect of nasal septum in >95% of cases
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| Etiology: some medications increase risk; septal deviation results in turbulent flow of air (more drying than laminar flow);
mucosa becomes dry, crusted, and prone to bleeding (eg, crusts may come off when patient washes face, blows nose, or rolls
over in bed); heated air exacerbates dryness and risk for epistaxis
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| Examination: crusted and clotted blood inside nose; granulation tissue may develop at site; instruments—headlight or
head mirror important to free hands for speculum and other instruments; headlight easier to use, but mirror eliminates shadows
(especially important for identifying location of posterior lesions); metal or disposable specula available; bayonet forceps
preferred over straight forceps (hand positioned outside line of sight); variety of suction tips needed for removing clots
from nose and throat; preparation—insert speculum with blades oriented to expand nostril vertically (important for viewing
septum)
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| Control of bleeding: insert cotton ball saturated with mixture of 2% lidocaine (eg, Xylocaine) and 1% oxymetazoline
(Afrin) or phenylephrine (Neo-Synephrine) mixed 50/50; or spray solution directly into nose, then place cotton ball (vessels
constrict, causing bleeding to slow or stop); silver nitrate—contact lesion to stop remainder of bleeding (speaker
uses wooden sticks topped with cotton balls of silver nitrate); suction excess to avoid damage to tissue; use caution when
inserting silver nitrate into nostril, because contacted skin turns black (fades in 2-3 wk); gels and ointments—various
products (eg, Vicks Vaporub, A+D ointment, white petrolatum [Vaseline], bacitracin) used to aid healing; reaching lesion
sometimes difficult with petroleum-based products; speaker prefers water-soluble saline gel; patient places ball of
gel on medial wall and sniffs vigorously 4 to 5 times each day until healed; saline spray less effective; additional
measures—oxidized cellulose (Surgicel) dressing dissolves over time; 2 to 3 layers applied between middle turbinate
and septum decrease chance for recurrence
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| Packing: bleeding not controlled with silver nitrate may require placement of anterior or posterior pack; compressed
sponge (Merocel) pack—hard material may abrade nose during placement; pack softens as it fills with blood but can
abrade tissue during removal (3 days later), restarting bleeding; Vaseline strip gauze—packs effective but uncomfortable;
placement requires skill; balloon packs—1 or 2 balloons, for anterior and posterior bleeds; gauze packs—layers
span front to back, top to bottom of nasal cavity (requires 6 ft of 1-in gauze; very uncomfortable); saline-filled balloon
packs—air diffuses quickly; balloons filled with saline maintain pressure
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| Prophylaxis: patients with packed noses require antibiotics because of increased risk for toxic shock; pain medication often
necessary; bilateral nasal packs—patients breathe less and may develop hypoxia; pain medication may exacerbate condition;
after placement of bilateral pack, monitor blood pressure and consider discontinuing medications that aggravate bleeding
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| Follow-up: leave packs in place for 3 days; continued bleeding—if problem continues, consider embolization (preferred
by speaker) or vessel ligation
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| NASAL POLYPOSIS: A CLINICAL-PATHOLOGICAL PERSPECTIVE —Andrew H. Murr, MD, Professor and Vice
Chairman, Department of Otolaryngology-Head and Neck Surgery, University of California, San Francisco, School of
Medicine
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| Epidemiology: 37 million patients afflicted with sinusitis each year; asthma—7% of adults with asthma, 13% of patients
with intrinsic asthma, and 5% of patients with atopic asthma have polyps; chronic rhinosinusitis—5% of patients with
nonallergic and 1.5% of patients with allergic rhinitis have polyps; children—polyps uncommon; disorders—nasal polyps
common in patients with aspirin intolerance, cystic fibrosis, and Churg-Strauss syndrome; 85% of patients with allergic
fungal sinusitis (AFS) have polyps
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| Anatomy: role in development of polyps uncertain; studies using radiolabeled mist indicate hiatus semilunaris, uncinate
process, and anterior middle meatus as primary sites of deposition; insult caused by particulate matter may cause inflammatory
cascade and increase risk for polyposis in these areas; exceptions—polyps occur throughout nasal lining in patients
with systemic pathologies (eg, aspirin triad, cystic fibrosis, AFS, primary ciliary dyskinesia); antral choanal polyps
develop in maxillary sinus, then expand outward, leaving ethmoid sinuses clear
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| Examination: complaints—nasal obstruction most common; fullness or pressure may occur, but pain uncommon; some
patients experience asthma exacerbation and anosmia; endoscopy—reveals subtle findings and overall distribution of
polyps; radiologic studies—computed tomography (CT) mainstay of imaging; magnetic resonance imaging (MRI)
helpful in complex cases and differentiates inspissated secretions from tumors; problems—presence of viral upper respiratory
infections (URIs), especially during first 3 days, interferes with interpretation of CT; abnormalities inaccurately
attributed to sinus disease in 87% of patients; speaker emphasizes importance of “looking at your own CTs” when evaluating
patients with polyps or chronic sinus disease
|
| Etiology: polyps require categorization since they represent end-phenotypic expression of various disease processes and
inflammatory insults; understanding specific etiology important for targeting treatment; chronic rhinosinusitis—
dividing patients into groups based on presence or absence of polyps may prove useful for assessing treatment outcomes
|
| Viral polyps: human papillomavirus (HPV) types 6 and 11 prevalent in inverted papilloma; progression—rate of malignant
transformation 15%; high rate of local recurrence; treatment—open medial maxillectomy or endoscopic approach;
transmission—unclear whether sexual transmission occurs
|
| Aspirin triad: first case of respiratory reaction induced by aspirin reported within 1 yr of its introduction; aspirin triad (aspirin
sensitivity, nasal polyposis, and asthma) identified in 1968; mechanism—inhibition of cyclooxygenase-1 (COX-1)
decreases prostaglandin E2 (PGE2); relative up-regulation of leukotrienes results in chronic inflammation and formation
of polyps; increasing COX-1 blockade exacerbates asthma symptoms, and decreasing COX-1 blockade decreases asthma
symptoms in these patients; many patients have cross-sensitivities with other drugs and foods; treatment—aspirin and
salicylate avoidance (foods that contain salicylates include beer, cheese, and celery); topical and systemic corticosteroids
effective; leukotriene inhibitors less effective; surgery has high rate of recurrence; aspirin desensitization—aspirin challenges
can reduce leukotriene response and decrease symptoms
|
| AFS and polyposis: IgE-mediated type I Gell and Coombs reaction; examination reveals Charcot-Leyden crystals, elevated
IgE, characteristic findings on CT, and pathologic evidence of fungus; responds to corticosteroids; etiology—role
of fungus in sinus disease debated; eosinophils may act as mediators in allergic immune response; treatment—surgery;
immune desensitization; topical and systemic corticosteroids; antifungal agents may have role, but longitudinal studies
needed
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| Bacterial etiology: Staphylococcus aureus endotoxin may play role in eosinophil response seen in some patients with
chronic rhinosinusitis; treatment includes doxycycline and corticosteroids; disease mechanism in patients without S aureus
involves neutrophils, and treatment includes culture-directed antibiotics
|
| Epidermal growth factor receptor (EGFR) theory: polyps contain normal pseudostratified epithelium and hyperplastic
epithelium; epithelial damage may cause hyperplasia; EGFR regulates production of mucin and goblet cell hyperplasia;
evidence from rat model and studies of human tracheal epithelium suggest involvement in upper airway
inflammatory disease; mechanism—eosinophils produce tumor necrosis factor-á (TNF-á) which induces expression of
EGFR; hyperplastic epithelium produces larger quantities of EGFR than normal epithelium; MUC5AC gene that regulates
production of mucin controlled by EGFR; future treatments may involve blocking EGFR (drug trials in progress)
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| Atopy: inhalant allergy common, but <25% of patients with positive skin tests have polyps; IgE often evident on smears
of nasal secretions from patients with polyps, but may not represent inhalant allergy; ie, eosinophilia and IgE may play
role in pathophysiology of nasal polyps, but not necessarily related to atopic allergic rhinitis
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| Other factors: anatomic—mucoceles (plugged sinus and bone erosion); mucus retention cyst (plugged mucus gland;
appears similar to polyp on imaging); accessory ostia often found in posterior fontanelle; genetic—cystic fibrosis (CF)
involves abnormalities on chromosome 7; 50 mutations (of 550 mutations seen in CF patients) associated with nasal
polyposis; patients with Ä-F508/G551D mutation also have increased growth of Pseudomonas (significance unknown);
environmental—many substances (eg, recreational drugs, pesticides, water additives, food preservatives, plastics and
synthetic fibers, insulation material) suspected of having role in polyposis, but conclusive evidence does not exist
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| Treatment strategies: anti-inflammatory agents (eg, corticosteroids, EGFR-blockers, agents that stimulate COX cascade);
immunotherapy; environmental avoidance; surgery; genetic engineering; note—identification of causative insult and specific
mechanism of inflammation important for directing treatment; systemic inflammatory conditions best treated with technology
directed at global (rather than local) control of inflammation
|
| HPV: UPDATE ON TREATMENT STRATEGIES —Joel Palefsky, MD, CM, Professor, Department of Medicine, Division of
Infectious Diseases, University of California, San Francisco, School of Medicine
|
| Recurrent respiratory papillomatosis (RRP): 2000 to 2500 new cases each year; juvenile-onset disease (<5 yr of
age) more common and more aggressive than adult-onset; disease associated with HPV infection; HPV—75% of sexually
active adults infected with genital HPV during lifetime; genital warts common presentation, but infections often subclinical
|
| HPV genotypes: >100 viral genotypes, each with specific niche within skin; oncogenic genotypes—HPV-16 accounts
for 50% of cervical cancers; HPV-18 accounts for 20% of cervical cancers; nononcogenic genotypes—HPV-6 and
HPV-11 associated with genital warts and respiratory papillomatosis; warts present at time of delivery, and infant aspirates
virus while passing through birth canal; nononcogenic types also cause plantar and palmar warts
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| Viral proteins: E6 and E7 major oncoproteins of HPV; L1 major capsid protein; in vitro, L1 autoassembles into 3-dimensional
structure resembling native viral particle; antibodies needed to prevent HPV infection conformation-dependent;
antibodies generated using virus-like particles from L1 autoassembly much more effective in preventing HPV entry
into cells and can be used in vaccines; E7 oncoprotein inactivates retinoblastoma protein (important negative regulator of
cell growth); E6 oncoprotein binds p53 (another cell-cycle regulator) and leads to its destruction
|
| Pathogenesis: most cases of RRP caused by HPV-6 or HPV-11; occasionally, oncogenic types descend into lungs and
cause invasive squamous cell carcinoma; risk factors—exposure to HPV at delivery (HPV-11 more common); polymorphism
in oncoproteins may affect aggressiveness; HLA type has role in cell-mediated immunity; abnormalities in
transporter protein, TAP1, affect antigen presentation on surface of cell and decrease immune response
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| Surgery: mainstay of therapy, but recurrence common; HPV infects basal cells; removal of lesion does not eradicate dormant
HPV from adjacent cells; literature on adjuvant therapy—studies typically contain small numbers of patients, mixtures of
adult-onset and juvenile-onset disease, and variation in multiple factors, including severity of disease at baseline, dosing regimens,
timing of surgery, outcome measures, and length of follow-up
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| Interferon: nonspecific adjuvant therapy with response rates of 30% to 60%; use has decreased, partly because of adverse
effects (severe flu-like symptoms, hepatic and renal dysfunction) and availability of other therapies
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| Indole-3 carbinol (I3C): active against variety of cancers; main antioxidant in broccoli; mechanism—may affect estrogens
(hormone-response elements present in HPV); may induce arrest of cell cycle by inhibiting cyclin-dependent kinase;
study—of 33 patients, 33% experienced complete response, 33% had partial response, and 33% had no response;
complete response occurred in only 1 of 9 pediatric patients
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| Cidofovir: activity against genital warts reported, but no large controlled trials performed; mechanism unknown; molecule
appears to undergo phosphorylation; interferes with viral DNA polymerase (absent in HPV); action against HPV may involve
down-regulation of oncoproteins; regimen—2.5 to 5.0 mg/mL injected into lesions every 2 to 3 wk; adverse effects—
generally well tolerated, but concern about local toxicity and carcinogenicity (adenocarcinoma seen in rats); studies—
several small studies conducted with children; rates of complete response varied from 25% to 63% (higher in adults); promising
therapy, but questions persist about optimal dosing, duration of therapy, long-term response, and risk for malignancy
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| Photodynamic therapy (PDT): studies using 2 different activating agents showed response to treatment, but latent virus
remained (problems with recurrence)
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| Therapeutic vaccines: fusion protein between heat-shock protein of Mycobacterium bovis (Hsp65) and E7 protein of
HPV16 activates immune response against E7 antigen (tumor-specific antigen essential for transformation and continuously
expressed); phase 2 study found length of time required between repeat surgeries increased from 55 days to 95
days; phase 3 study in progress
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| Prophylactic vaccines: bivalent vaccine active against HPV-16 and HPV-18; quadrivalent vaccine adds HPV-6 and HPV-
11; both vaccines appear 100% effective at preventing persistent infection with HPV-16 and HPV-18 when given to women
before initiation of sexual activity; quadrivalent vaccine also appears effective against genital warts; preventing HPV infection
in mothers should have major impact on incidence of RRP in children
|
Educational Objectives
| The goal of this activity is to provide the clinician with information about the management of epistaxis and advances in
treatment for nasal polyps and recurrent respiratory papillomatosis (RRP). After hearing and assimilating this program, the
clinician will be better able to:
|
 | 1. Control epistaxis and implement appropriate prophylactic measures with nasal packing.
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| 2. Review etiologies of nasal polyposis and implications for treatment.
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| 3. List anatomic, genetic, and environmental factors associated with nasal polyposis.
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| 4. Identify patients with RRP and design a management plan.
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| 5. Discuss the role of prophylactic vaccines against human papilloma virus (HPV) in future eradication of RRP.
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Discussed on This Program
Bacitracin [AK-Tracin, Altracin, Baciguent, Baci-IM]
Cidofovir [Forvade, Vistide]
Clopidogrel bisulfate [Plavix]
Doxycycline (several trade names)
Interferon (several formulations and trade names)
Lidocaine HCl [Xylocaine, others]
Oxymetazoline HCl [Neo-Synephrine, others]
Polymyxin B sulfate, neomycin, and bacitracin [Neosporin, others]
Warfarin sodium [Coumadin]
White petrolatum [Vaseline]
Suggested Reading
Bachert C, et al: The role of sinus disease in asthma. Curr Opin Allergy clin Immunol 6:29, 2006; Behrens DC:
Treatment of epistaxis in the emergency department. Emerg Med J 23:241, 2006; Derkay CS, Darrow DH: Recurrent
respiratory papillomatosis. Ann Otol Rhinol Larngol 115:1, 2006; Feusi B, et al: Posterior epistaxis: systematic review
on the effectiveness of surgical therapies. Rhinology 43:300, 2005; Garavello W, Gaini RM: Incidence of inverted
papilloma in recurrent nasal polyposis. Laryngoscope 116:221, 2006; Kahn JA: vaccination as a prevention strategy for
human papillomavirus-related diseases. J Adolesc Health 37(6 Suppl):S10, 2005; Kieff DA, Busaba NY: Efficacy of
montelukast in the treatment of nasal polyposis. Ann Otol Rhinol Laryngol 114:941, 2005; Kitapci F, et al: Role of
mast and goblet cells in the pathogenesis of nasal polyps. J Otolaryngol 35:122, 2006; Mayeaux EJ Jr.: Harnessing the
power of prevention: human papillomavirus vaccines. Curr Opin Obstet Gynecol 18(Suppl 1):S15, 2006; Skillbeck CJ,
Oakley R: The fist model for nasal packing. Eur J Emerg Med 13:97, 2006; Spanos WC, et al: Cidofovir incorporation
into human keratinocytes with episomal HPV 16 results in nonselective cytotoxicity. Ann Otol Rhinol Laryngol
114:840, 2005; Stjarne P, et al: A randomized controlled trial of mometasone furoate nasal spray for the treatment of
nasal polyposis. Arch Otolaryngol Head Neck Surg 132:179, 2006; Umapthy N, et al: Persistent epistaxis: what is the
best practice? Rhinology 43:305, 2005; Viehweg TL, et al: Epistaxis: diagnosis and treatment. J Oral Maxillofac Surg
64:511, 2006.
Faculty Disclosure
In adherence to ACCME guidelines, the Audio-Digest Foundation requests all lecturers to disclose any significant financial
relationship with the manufacturer or provider of any commercial product or service discussed. The following has been disclosed:
Dr. Palefsky receives grant support from Merck.
Dr. Roberts was recorded in Naples, Florida at ENT Disorders for the Primary Care Practitioner, sponsored by
Cleveland Clinic Florida, and held March 19, 2005; Drs. Murr and Palefsky were recorded in San Francisco at Otolaryngology
Update, sponsored by the Department of Otolaryngology-Head and Neck Surgery, University of California,
San Francisco, School of Medicine and held November 10-12, 2005. The Audio-Digest Foundation thanks the
speakers and the sponsors for their cooperation in the production of this program.
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