Lack of prognostic effect of carbonic anhydrase-9, hypoxia inducible factor-1α and bcl-2 in 286 patients with early squamous cell carcinoma of the glottic larynx treated with radiotherapy.

AIMS: To evaluate the prognostic significance of potential tumour markers of hypoxia and apoptosis in early squamous cell carcinoma of the glottic larynx managed with radiotherapy. MATERIALS AND METHODS: In total, 382 patients with T1 and T2 squamous cell carcinoma of the glottic larynx (vocal cords) received radical radiotherapy (50-55 Gy, in 16 fractions in 98% of cases). Pre-treatment haemoglobin was available for 328 patients; biopsy samples were available for 286. Immunohistochemistry was carried out for carbonic anhydrase-9 (CA-9), hypoxia inducible factor-1α (HIF-1α) and Bcl-2. RESULTS: At 5 years, locoregional control was achieved in 88.2%, cancer-specific survival in 95.0% and overall survival in 78.7%. Adverse prognostic factors for locoregional tumour recurrence were pre-treatment haemoglobin <13.0 g/dl (P = 0.035, Log rank test; sensitivity 0.28, specificity 0.84) and stage T2 rather than T1 (P = 0.002). The effect of haemoglobin level on locoregional control was not significant when stratified by the median of 14.2 g/dl (P = 0.43) or as a continuous variable (P = 0.59). High CA-9 (P = 0.11), HIF-1α (P = 0.67) and Bcl-2 (P = 0.77) expression had no prognostic significance. CONCLUSIONS: High CA-9, HIF-1α and Bcl-2 do not add to the prognostic significance of tumour stage and lower haemoglobin in predicting failure of local control in early glottic larynx squamous cell carcinoma managed with radiotherapy. The effect of haemoglobin was not strong enough to be useful as a prognostic biomarker.

Rhabdomyosarcoma of the trachea: first reported case treated with proton beam therapy.

OBJECTIVE: We report a case of rhabdomyosarcoma of the trachea in a 14-month-old child, and we present the first reported use of proton beam therapy for this tumour. CASE REPORT: A 14-month-old girl presented acutely with a seven-day history of biphasic stridor. Emergency endoscopic debulking of a posterior tracheal mass was undertaken. Histological examination revealed an embryonal rhabdomyosarcoma with anaplasia. Multimodality therapy with surgery and chemotherapy was administered in the UK, and proton beam therapy in the USA. CONCLUSION: Only three cases of rhabdomyosarcoma of the trachea have previously been reported in the world literature. This is the first reported case of treatment of this tumour with proton beam therapy. Compared with conventional radiotherapy, proton beam therapy may confer improved long-term outcome in children, with benefits including reduced irradiation of the spinal cord.

Unilateral transverse cordotomy for bilateral abductor vocal fold immobility.

OBJECTIVE: We present a case series with airway compromise due to bilateral abductor vocal fold paralysis or fixation, treated with unilateral transverse cordotomy. METHODS: Of eight consecutive patients with dyspnoea due to bilateral paramedian vocal fold immobility, seven underwent unilateral transverse cordotomy between August 2006 and April 2010 at University Hospital of South Manchester, UK. Airway and voice outcomes were compared before and after surgery. RESULTS: All seven treated cases derived subjective airway function improvement; there was no aspiration. The eighth case had inadequate access. None of the seven treated patients required contralateral cordotomy or permanent tracheostomy. One treated case required a temporary tracheostomy; unilateral transverse cordotomy facilitated eventual decannulation. Two patients died of cancer at five and six weeks, variously. At a mean follow up of 22 months, four cases showed unchanged or slightly worse Voice Symptom Scale and Grade-Roughness-Breathiness-Asthenia-Strain scale scores. CONCLUSION: In patients with bilateral abductor vocal fold immobility, unilateral transverse cordotomy results in improved dyspnoea with either no voice change or only slight worsening. This is a more conservative procedure than bilateral transverse cordotomy, with the potential for better preservation of voice and breath support.

Superficial temporal artery pseudoaneurysm: first reported case after parotid surgery.

OBJECTIVE: To describe a case of superficial temporal artery pseudoaneurysm occurring as a rare complication of parotid surgery (to the authors' knowledge, the first such case reported), to review the aetiology of superficial temporal artery pseudoaneurysm, and to highlight pseudoaneurysm as a cause of facial swelling after parotidectomy. METHOD: A literature search of the PubMed and EMBASE databases was carried out using the Medical Subject Heading key words 'superficial temporal artery', 'aneurysm', 'pseudoaneurysm' and 'parotid'. RESULT: No previously reported cases of superficial temporal artery aneurysm or pseudoaneurysm following parotid surgery were identified. CONCLUSION: Pseudoaneurysm of the superficial temporal artery is a rare complication of parotid surgery which has not previously been reported.

An approach to bilateral bone-anchored hearing aid surgery in children: contralateral placement of sleeper fixture.

OBJECTIVE: Bone-anchored hearing aid surgery in younger children is a two-stage procedure, with a titanium fixture being allowed to osseointegrate for several months before an abutment is fitted through a skin graft. In the first procedure, it has been usual to place a reserve or sleeper fixture approximately 5 mm from the primary fixture as a backup in case the primary fixture fails to osseointegrate. This ipsilateral sleeper fixture is expensive, is often not used, and is placed in thinner calvarial bone where it is less likely to osseointegrate successfully. The authors have implanted the sleeper fixture on the contralateral side, with the additional objective of reducing the number of procedures for bilateral bone-anchored hearing aid implantation, providing a cost-effective use for the sleeper. METHODS: The authors implanted the bone-anchored hearing aid sleeper fixture in the contralateral temporal bone instead of on the ipsilateral side in seven successive paediatric cases with bilateral conductive hearing loss requiring two-stage bone-anchored hearing aids, treated at the Royal Manchester Children's Hospital, UK. RESULTS: The seven patients ranged in age from five to 15 years, with a mean age of 10 years; in addition, a 20-year-old with learning disability was also treated. In each case, the contralateral sleeper fixture was not needed as a backup fixture, but was used in four patients (57 per cent) as the basis for a second-side bone-anchored hearing aid. CONCLUSIONS: In children with bilateral conductive hearing loss, in whom a bilateral bone-anchored hearing aid is being considered and the second side is to be operated upon at a later date, we recommend placing the sleeper fixture on the contralateral side at the time of primary first-side surgery. Our technique provides a sleeper fixture located in an optimal position, where it also offers the option of use for a second-side bone-anchored hearing aid and reduces the number of procedures needed.

Resistance of Pseudomonas to ciprofloxacin: implications for the treatment of malignant otitis externa.

For fifteen years oral ciprofloxacin has been the standard treatment for malignant otitis externa, a sometimes fatal osteomyelitis of the skull base usually caused by Pseudomonas aeruginosa. Resistance to ciprofloxacin is developing. Over a 16-month period, we saw five cases where malignant otitis externa progressed, with the development of cranial nerve palsies in four cases, despite oral ciprofloxacin. Prolonged intravenous antibiotic therapy became necessary. One case was managed largely as an out-patient, but four patients spent many weeks in hospital. Only two cases had diabetes and this was monitored and controlled. Pseudomonas aeruginosa was isolated in four of the five cases, but antibiotic sensitivity to ciprofloxacin was not determined. In one case a later isolate was tested and found to be ciprofloxacin resistant. Progress was monitored by serial C-reactive protein (CRP) and white cell count. For diagnosis and assessing response to treatment we considered serial magnetic resonance imaging or computed tomography more useful than isotope bone scan. There must be a readiness to use intravenous antibiotics, as a response to ciprofloxacin can no longer be assumed. Bacterial isolates must be tested for sensitivity to antibiotics including ciprofloxacin, and further biopsy and culture are essential if treatment fails.

Sore throat in adults--does the introduction of a clinical scoring system improve the management of these patients in a secondary care setting?

OBJECTIVE: To audit sore throat management in adults, introduce proforma-based guidelines and to re-audit clinical practice. SETTING: Adult emergency department of an inner city teaching hospital. METHODS: A literature search was carried out to identify relevant guidelines. In stage one, patients presenting to the emergency department with sore throat were identified retrospectively from the emergency department attendance register. Proformas were completed retrospectively. In stage two, new guidelines were introduced and staff educated about the guidelines. In stage three, patients presenting with sore throat were identified at triage and proformas were completed at time of consultation. OUTCOME MEASURES: (1) appropriate clinical assessment of the likelihood of bacterial infection using the clinical scoring system, (2) appropriateness of antibiotic prescription, (3) recommendation of supportive treatments to patients. RESULTS: Introduction of a clinical scoring system reduced the inappropriate prescribing of antibiotics from 44 per cent to 11 per cent. Correct antibiotic prescription rose from 60 per cent to 100 per cent. Although the variety of advice given about supportive treatment increased, the actual number of patients receiving documented supportive advice fell from 67.8 per cent in stage one to 58 per cent in stage three. CONCLUSION: The introduction of clinically based guidelines for the diagnosis and management of sore throat in adults can reduce inappropriate antibiotic prescribing.

Localization and quantitation of eotaxin mRNA in human nasal polyps.

Nasal Polyps (NPs) are the most common mass lesions found in the nose. NPs cause airway obstruction, prevent normal sinus function, and can lead to infection of the eye, facial bones and central nervous system. The predominant cell type inhabiting NPs is the eosinophil, and the chemokine eotaxin is believed to play an important role in NP eosinophilia. The objective of this study was to localize and quantitate expression of eotaxin mRNA in human NPs. Total RNA was isolated from NPs that were collected from 5 patients who had undergone polypectomy. Portions of these polyps were also fixed in formalin, embedded in paraffin, and sectioned onto slides for use in in situ hybridization. Total RNA from one patient was used in a reverse transcriptase polymerase chain reaction using eotaxin specific primers to generate a human eotaxin cDNA. The eotaxin cDNA was cloned and used to generate probes for Northern blot analyses and for use in in situ hybridization (ISH). Eotaxin mRNA was detected by Northern analyses in all patient samples, though the relative expression level in each patient varied. ISH localized the expression of eotaxin mRNA specifically in eosinophils in 2 of the 3 patients in the study for whom the embedded polyp tissue appeared sufficiently well preserved for mRNA localization. Our findings suggest that eosinophilia in NPs is likely a self-amplification process whereby increasing numbers of eosinophils are recruited to enter the polyp as a result of production of eotaxin by eosinophils already within the polyp.

Molecular typing of paired bacterial isolates from the adenoid and lateral wall of the nose in children undergoing adenoidectomy: implications in acute rhinosinusitis.

OBJECTIVE: Recent studies have suggested that the origin of bacteria that enter the lateral wall of the nose and paranasal sinuses arise from the nasopharynx. The purpose of this study was to compare the molecular biological profiles of potential pathogens found in the nasopharynx and lateral wall of the nose concomittantly in children undergoing surgery for upper respiratory tract disease. STUDY DESIGN AND SETTING: Fifty-two children undergoing adenoidectomy for either tonsillectomy or adenoidectomy (hypertrophy) or otitis media with effusion were studied. Bacterial cultures were taken from the crypts of the adenoids and from the lateral wall of the nose under endoscopic control after sterilization of the vestibule and inferior turbinate. Routine cultures of these areas were performed in the bacteriology laboratory of the Children's Hospital of Buffalo. RESULTS: Bacterial pathogens were isolated from 79% of adenoids and 46% of lateral walls of the nose. Molecular typing of pairs of nontypable Haemophilus influenzae, Streptococcus pneumoniae, and Moraxella catarrhalis revealed that in 16 of 18 pairs (89%) the identical strain was present in both sites simultaneously. CONCLUSIONS: These results support the concept that when potential bacterial pathogens that may cause acute bacterial rhinosinusitis are found concomitantly in the nasopharynx and lateral wall of the nose, they are usually identical.

Fine needle aspiration biopsy of pediatric head and neck masses.

OBJECTIVE: To determine if fine needle aspiration (FNA) can preclude the requirement for diagnostic open biopsy in suspicious pediatric head and neck masses. METHODS: The records of 40 children presenting to an inner city tertiary care hospital who underwent a total of 50 FNA biopsies during the years 1988-1999 were reviewed. From these 40 patients, 17 children, aged 3 months to 18 years, underwent both clinically indicated FNA biopsy and subsequent open surgical biopsy or excision. Outcome measurements included clinical resolution or surgical pathologic diagnosis. RESULTS: The 17 patients who underwent open surgical biopsy subsequent to the FNA had a total of 21 FNAs performed. Three of these patients had more than one needle biopsy prior to surgery. The histologic diagnosis of the surgical excision confirmed the FNA biopsy cytologic diagnosis in all but two cases. FNA cytologic diagnostic categories included reactive lymph node/non-specific inflammation (25 biopsies), benign cystic process (four), granulomatous disease (eight), malignant neoplasm (three), and benign neoplasm (one). Eight of nine FNAs initially non-diagnostic had either complete resolution of the mass or a diagnosis obtained by subsequent FNA or open biopsy. CONCLUSIONS: FNA is a valuable diagnostic tool in the management of children with the clinical presentation of a suspicious neck mass. The technique reduces the need for more invasive and costly procedures. Early surgical biopsy, however, should be considered in rapidly enlarging masses, in the presence of persistent systemic symptoms, and when repeated FNA cytology is non-diagnostic.

Detection of intracytoplasmic cytokines by flow cytometry in adenoids and peripheral blood lymphocytes of children.

Cytokine flow cytometry at the single-cell level has never been utilized in the study of adenoidal lymphocytes. We describe the multiparameter capability of flow cytometry to simultaneously detect an antigen on the surface of the adenoidal and peripheral blood lymphocytes and detect Th1 and Th2 cytokines within the cytoplasm of these lymphocytes. The data suggest that the percentage of cells producing interferon (IFN)-gamma are decreased in adenoidal as compared to peripheral blood lymphocytes, confirming our previous studies. The new findings show that the CD8 subset of adenoidal lymphocytes produces lower amounts of IFN-gamma as compared to peripheral blood CD8 cells. The intracytoplasmic synthesis of interleukin (IL)-2, however, appears to be similar in both adenoidal and peripheral blood lymphocytes. The CD4 subset of lymphocytes in the adenoid produces more IL-2, whereas the CD8 subset produces more IFN-gamma. Finally, as shown in our previous studies, the Th2 cytokines appear to be produced in similar quantities in both adenoidal and peripheral blood lymphocytes.

The molecular biology of nasal polyposis.

The molecular biologic events in the development of nasal polyps are now becoming unraveled. It appears that eosinophils are the dominant inflammatory cell present in this tissue. The events leading up to the extravasation of eosinophils into the lamina propria nasal polyps are regulated by the proinflammatory cytokines tumor necrosis factor-alpha and interleukin-1 beta. These cytokines upregulate very late antigen-4 on the surface of eosinophils and vascular cell adhesion molecule-1 on the surface of the endothelial blood vessel. Chemokines such as RANTES (regulated upon activation, normal T-cell expressed and secreted) and eotaxin are responsible for the movement of eosinophils into the lamina propria of the nasal polyp. The release of major basic protein has an effect on alteration of the epithelial architecture and on the sodium and chloride flux into and out of the apical epithelial cell of the tissue. Finally, the alteration of the surface epithelium results in a defect in the migration of the cystic fibrosis transmembrane regulator protein to the apical surface. These two events, the release of major basic protein from the eosinophil and the alteration of the architecture of the surface epithelium, lead to an increase in sodium absorption and resultant edema: the hallmark of the pathology of the nasal polyp.

Intracranial complications of acute mastoiditis.

OBJECTIVE: Oral antibiotic use may have changed the incidence and microbiology of otitic intracranial complications. We reviewed cases of acute mastoiditis to document: (1) incidence of intracranial complications; (2) risk factors; and (3) identify pathologic organisms. METHODS: A retrospective study of children at a tertiary care children's hospital with acute mastoiditis from July, 1986 through June, 1998. RESULTS: 118 children with acute mastoiditis were identified. Eight patients (6.8%), ages 20 months to 14 years, had intracranial complications related to acute mastoiditis. Three children had a sigmoid sinus thrombosis, two children had an epidural abscess, and two children had both complications of sigmoid sinus thrombosis and epidural abscess, and a sigmoid sinus thrombosis and meningitis was present in one child. Pre-admission oral antibiotics were administered for an average of 10 days in seven of the eight patients. Persistent otorrhea and/or otalgia were present in all patients. Intraoperative cultures were negative in four cases (50%). Organisms isolated included: Streptococcus pneumoniae (2); Proteus mirabilis (1); Pseudomonas aeruginosa (1); and coagulase negative Staphylococcus (1). Multi-drug resistant organisms were documented in only one case. All patients underwent a contrast enhanced CT of the temporal bones and brain. Surgical management included complete mastoidectomy in all patients and a pressure equalization tube in seven of the eight cases. CONCLUSIONS: Our review did not document an increase in the incidence of otitic intracranial complications. Persistent otalgia or otorrhea while on oral antibiotics with associated neurologic symptoms are ominous signs suggestive of a complication. Multi-drug resistant organisms are uncommon whereas negative intraoperative cultures are common.

Geographic variation in allergic fungal rhinosinusitis.

Allergic fungal rhinosinusitis (AFRS) has a worldwide distribution. This survey of 20 otolaryngologic practices throughout the United States confirmed a variation in the frequency of AFRS relative to endoscopic sinus procedures performed for all other diagnoses. The highest incidence occurred in Memphis, Tennessee at 23%, with three other southern practices reporting a frequency of at least 10%. In the northern locations the frequency ranged from 0 to 4%. No correlation with mould counts was demonstrated, possibly because of incomplete mould data relative to most of the surgical locations.

Bacteria-mucin interaction in the upper aerodigestive tract shows striking heterogeneity: implications in otitis media, rhinosinusitis, and pneumonia.

The mucociliary system of the upper and lower respiratory tracts is a critical nonspecific pathway for the elimination of bacteria and other particulate matter. The interaction between bacteria and purified mucin of the upper and lower respiratory tracts has been a major focus of our laboratory for the past decade. We have previously demonstrated that nontypable Haemophilus influenzae and Moraxella catarrhalis adhere to human purified nasopharyngeal mucin and human middle ear mucin by a very limited number of specific outer membrane proteins. There have been no previous studies on the interaction of Streptococcus pneumoniae and purified mucin. Such information would be of extreme importance in identifying specific mechanisms of preventing colonization of this important pathogen to nasopharyngeal mucin. Using an overlay technique of purified radiolabeled mucins of the upper and lower respiratory tracts in a solid phase assay with 4 predominant pathogens of the upper and lower respiratory tracts, we found a striking heterogeneity of bacteria-mucin interaction. The implications of these interactions in the development of otitis media, rhinosinusitis, and lower respiratory infections are briefly discussed.

Management and complications of congenital dacryocele with concurrent intranasal mucocele.

INTRODUCTION: The association of dacryocele and intranasal mucocele has been previously reported. Its incidence and optimal treatment are unknown. PATIENTS AND METHODS: A retrospective review of 22 patients with 30 dacryoceles was performed to determine the mean age at presentation, sex distribution, and prevalence of associated intranasal mucocele, associated dacryocystitis, and respiratory distress. The components of the examination, ancillary tests, treatment modalities, and treatment outcomes were then summarized. RESULTS: Unilateral dacryoceles were seen in 16 (73%) of the infants, and bilateral dacryoceles were seen in 6 (27%) of the infants. Four (25%) of the 16 patients who initially had unilateral dacryoceles later developed bilateral dacryoceles. Dacryocystitis, preseptal cellulitis, or both were present on presentation or developed in 18 (60%) of 30 dacryoceles. Nasal endoscopy was performed on 13 (59%) of 22 patients. Nasal examination with nasal speculum and headlight was performed on 7 patients (32%). A concurrent intranasal mucocele was diagnosed in 23 (77%) of 30 dacryoceles. Respiratory distress arose in 5 (71%) of 7 patients with bilateral intranasal mucoceles and in 2 (22%) of 9 patients with a unilateral intranasal mucocele. Thirty-four procedures were performed. Seven dacryoceles (21%) were treated with nasolacrimal duct probing under topical anesthesia. Another one (3%) was treated with needle aspiration with later definitive therapy. All other procedures were managed under general anesthesia. These included 2 nasolacrimal duct probings (6%), 2 probings with silicone tube placement (6%), 10 probings with intranasal mucocele marsupialization and silicone tube placement (29%), and 12 probings with marsupialization alone (35%). Two (29%) of the 7 probings performed under topical anesthesia failed, whereas all other procedures were successful. One dacryocele spontaneously resolved. CONCLUSIONS: Congenital dacryoceles are commonly associated with intranasal mucoceles, dacryocystitis, and preseptal cellulitis. Respiratory distress is common in bilateral cases. Bilateral nasolacrimal duct probing should be considered in unilateral cases because of the high incidence of occult contralateral involvement.

Waldeyer's ring and otitis media: the nasopharyngeal tonsil and otitis media.

This overview of the relationship between the nasopharyngeal tonsil and otitis media will review three important concepts: (1) Adenoid inflammation leads to inflammatory obstruction of the Eustachian tube; (2) early colonization of the adenoid with the three major bacterial pathogens of otitis media is the most important factor in the early pathogenesis of otitis media; (3) the local immune system in the adenoid particularly specific secretory IgA directed against both viruses and bacterial pathogens are probably genetically controlled and represent the immunological factor in protecting the host against invasion of these agents in the Eustachian tube and middle ear. This overview of the relationship between the adenoid and the development of otitis media emphasizes that nasopharyngeal colonization with the three major middle ear pathogens is among the most important risk factors in the pathogenesis of otitis media. Inasmuch as these pathogens normally reside in the nasopharynges of most healthy children, the factors which trigger development of otitis media need to be carefully evaluated. Among these two triggers are viral infections and upper respiratory tract allergy.

Cellular immune response of adenoidal and tonsillar lymphocytes to the P6 outer membrane protein of non-typeable Haemophilus influenzae and its relation to otitis media.

Cellular immune responses to the P6 outer membrane protein of non-typeable Haemophilus influenzae (NTHi) were determined in vitro by measuring immunoglobulin (Ig) secreting cells and lymphocyte proliferation in adenoidal and tonsillar lymphocytes from 19 children. Preliminary tests showed that P6 did not stimulate naive cells such as cord blood lymphocytes, but did stimulate sensitized cells in adenoids and tonsils. Cellular proliferation was significantly higher in adenoidal lymphocytes than in tonsillar lymphocytes (median: quadratile of stimulation index = 3.7:2.3-5.5 vs. 1.2:1.0-2.1, p < 0.02). A comparison between children with or without otitis media revealed that proliferative responses to P6 of adenoidal lymphocytes from children with otitis media were significantly decreased (2.0:1.8-3.6 vs. 3.7:2.3-5.5, p < 0.04). P6-specific antibody secreting cells were identified in a total of 14 adenoids and the number of cells secreting IgA was decreased in the otitis media group compared to controls (median: quadratile/10(6) cells = 435:359-499 vs. 755:593-1870, p < 0.05). Cultivation with P6 stimulated IgA secretion in children without otitis media, while no response was seen in children with otitis media (median: quadratile/10(6) cells = 1323:915-2410 vs. 2240:1900-2830, p < 0.02). These preliminary data demonstrate that lymphocytes from adenoids and tonsils recognize P6 as a specific antigen and that the adenoid is the more reactive of the two organs. Impaired P6-specific cellular immune responses of adenoids in children with otitis media may explain the recurrent nature of otitis media due to NTHi in the otitis prone population.