Search

Despite preclinical success, monotherapies targeting EGFR or cyclin D1-CDK4/6 in Head and Neck squamous cell carcinoma (HNSCC) have shown a limited clinical outcome. Here, we aimed to determine the combined effect of palbociclib (CDK4/6) and afatinib (panEGFR) inhibitors as an effective strategy to target HNSCC. Using TCGA-HNSCC co-expression analysis, we found that patients with high EGFR and cyclin D1 expression showed enrichment of gene clusters associated with cell-growth, glycolysis, and epithelial to mesenchymal transition processes. Phosphorylated S6 (p-S6), a downstream effector of EGFR and cyclin D1-CDK4/6 signalling, showed a progressive increase from normal oral tissues to leukoplakia and frank malignancy, and associated with poor outcome of the patients. This increased p-S6 expression was drastically reduced after combination treatment with afatinib and palbociclib in the cell lines and mouse models, suggesting its utiliy as a prognostic marker in HNSCC. Combination treatment also reduced the cell growth and induced cell senescence via increasing reactive oxygen species with concurrent ablation of glycolytic and tricarboxylic acid cycle intermediates. Finally, our findings in sub-cutaneous and genetically engineered mouse model (K14-CreERtam;LSL-KrasG12D/+;Trp53R172H/+) studies showed a significant reduction in the tumor growth and delayed tumor progression after combination treatment. This study collectively demonstrates that dual targeting may be a critical therapeutic strategy in blocking tumor progression via inducing metabolic alteration and warrants clinical evaluation.

to Examine the practice characteristics of same-day clinic appointments and the use of same-day appointment scheduling to provide access to care in an otolaryngology-head and neck surgery clinic.Retrospective chart review of same-day clinic appointments from January 1, 2016, to December 31, 2018, in patients aged19 years at a single academic center. Demographic data, diagnoses, procedures completed, and operations completed were analyzed.There were 2696 visits by 2324 patients during the 3-year study period. More men than women (57% vs 43%) made same-day appointments. The mean age was 50.7 years (range, 19-99 years). Sinonasal and otologic diagnoses were the most frequently coded. A total of 1452 procedures were completed on the day of the visit, and 239 operations were completed as a result of the visit. Overall, a broad spectrum of otolaryngology care was delivered within the organizational new patient access goals.Access to otolaryngology-head and neck surgery care can be challenging. Many patients will seek care when they feel they need it, and patient conditions can change unexpectedly. Offering same-day scheduling can allow patients timely health care and appropriate care.Same-day appointment scheduling can provide access to care and urgent care for patients. The department of otolaryngology-head and neck surgery has been able to maintain a high rate of providing new patient appointments within 10 days with this method. Further considerations for the impact of same-day scheduling on no-show rates and patient satisfaction can be evaluated.

African Americans (AA) with Head and Neck Squamous Cell Carcinoma (HNSCC) have a worse disease prognosis than White patients despite adjusting for socio-economic factors, suggesting the potential biological contribution. Therefore, we investigated the genomic and immunological components that drive the differential tumor biology among race. We utilized the cancer genome atlas and cancer digital archive of HNSCC patients (1992–2013) for our study. We found that AA patients with HNSCC had a higher frequency of mutation compared to Whites in the key driver genes—P53, FAT1, CASP8 and HRAS. AA tumors also exhibited lower intratumoral infiltration of effector immune cells (CD8(+), γδT, resting memory CD4(+) and activated memory CD4(+) T cells) with shorter survival than Whites. Unsupervised hierarchical clustering of differentially expressed genes demonstrated distinct gene clusters between AA and White patients with unique signaling pathway enrichments. Connectivity map analysis identified drugs (Neratinib and Selumetinib) that target aberrant PI3K/RAS/MEK signaling and may reduce racial disparity in therapy response.

Cancer remains a leading cause of death in the USA and around the world. Although the current synthetic inhibitors used in targeted therapies have improved patient prognosis, toxicity and development of resistance to these agents remain a challenge. Plant-derived natural products and their derivatives have historically been used to treat various diseases, including cancer. Several leading chemotherapeutic agents are directly or indirectly based on botanical natural products. Beyond these important drugs, however, a number of crude herbal or botanical preparations have also shown promising utility for cancer and other disorders. One such natural resource is derived from certain plants of the family Annonaceae, which are widely distributed in tropical and subtropical regions. Among the best known of these is Annona muricata, also known as soursop, graviola or guanabana. Extracts from the fruit, bark, seeds, roots and leaves of graviola, along with several other Annonaceous species, have been extensively investigated for anticancer, anti-inflammatory and antioxidant properties. Phytochemical studies have identified the acetogenins, a class of bioactive polyketide-derived constituents, from the extracts of Annonaceous species, and dozens of these compounds are present in different parts of graviola. This review summarizes current literature on the therapeutic potential and molecular mechanism of these constituents from A.muricata against cancer and many non-malignant diseases. Based on available data, there is good evidence that these long-used plants could have both chemopreventive and therapeutic potential. Appropriate attention to safety studies will be important to assess their effectiveness on various diseases caused or promoted by inflammation.

// Muzafar A. Macha 1, 2 , Satyanarayana Rachagani 2 , Asif Khurshid Qazi 2 , Rahat Jahan 2 , Suprit Gupta 2 , Anery Patel 3 , Parthasarathy Seshacharyulu 2 , Chi Lin 4 , Sicong Li 4 , Shuo Wang 4 , Vivek Verma 4 , Shosei Kishida 5 , Michiko Kishida 5 , Norifumi Nakamura 6 , Toshiro Kibe 6 , William M. Lydiatt 1 , Russell B. Smith 1 , Apar K. Ganti 3, 7 , Dwight T. Jones 1 , Surinder K. Batra 2, 8, 9 , Maneesh Jain 2, 8 1 Department of Otolaryngology/Head and Neck Surgery, University of Nebraska Medical Center, Omaha, NE 68198, USA 2 Department of Biochemistry and Molecular Biology, University of Nebraska Medical Center, Omaha, NE 68198, USA 3 Department of Internal Medicine, University of Nebraska Medical Center, Omaha, NE 68198, USA 4 Department of Radiation Oncology, University of Nebraska Medical Center, Omaha, NE 68198, USA 5 Department of Biochemistry and Genetics, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima 890-8544, Japan 6 Department of Oral and Maxillofacial Surgery, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima 890-8544, Japan 7 VA Nebraska Western Iowa Health Care System and University of Nebraska Medical Center, Omaha, NE 68198, USA 8 Buffett Cancer Center, Omaha, NE 68198, USA 9 Eppley Institute for Research in Cancer and Allied Diseases, University of Nebraska Medical Center, Omaha, NE 68198, USA Correspondence to: Muzafar A. Macha, email: muzafar.macha@unmc.edu Keywords: head and neck squamous cell carcinoma (HNSCC), afatinib, radiosensitization Received: November 02, 2016 Accepted: February 06, 2017 Published: February 18, 2017 ABSTRACT The dismal prognosis of locally advanced and metastatic squamous cell carcinoma of the head and neck (HNSCC) is primarily due to the development of resistance to chemoradiation therapy (CRT). Deregulation of Epidermal Growth Factor Receptor (EGFR) signaling is involved in HNSCC pathogenesis by regulating cell survival, cancer stem cells (CSCs), and resistance to CRT. Here we investigated the radiosensitizing activity of the pan-EGFR inhibitor afatinib in HNSCC in vitro and in vivo . Our results showed strong antiproliferative effects of afatinib in HNSCC SCC1 and SCC10B cells, compared to immortalized normal oral epithelial cells MOE1a and MOE1b. Comparative analysis revealed stronger antitumor effects with afatinib than observed with erlotinib. Furthermore, afatinib enhanced in vitro radiosensitivity of SCC1 and SCC10B cells by inducing mesenchymal to epithelial transition, G1 cell cycle arrest, and the attenuating ionizing radiation (IR)-induced activation of DNA double strand break repair (DSB) ATM/ATR/CHK2/BRCA1 pathway. Our studies also revealed the effect of afatinib on tumor sphere- and colony-forming capabilities of cancer stem cells (CSCs), and decreased IR-induced CSC population in SCC1 and SCC10B cells. Furthermore, we observed that a combination of afatinib with IR significantly reduced SCC1 xenograft tumors (median weight of 168.25 ± 20.85 mg; p = 0.05) compared to afatinib (280.07 ± 20.54 mg) or IR alone (324.91 ± 28.08 mg). Immunohistochemical analysis of SCC1 tumor xenografts demonstrated downregulation of the expression of IR-induced pEGFR1, ALDH1 and upregulation of phosphorylated γH2AX by afatinib. Overall, afatinib reduces tumorigenicity and radiosensitizes HNSCC cells. It holds promise for future clinical development as a novel radiosensitizer by improving CSC eradication.

Background: Notch1 and its intracellular cytoplasmic domain (NICD) are dysregulated in many solid tumors, including head and neck squamous cell carcinoma (HNSCC), and associated with disease initiation and progression. NICD-mediated upregulation of nuclear receptor related 1 (NURR1/NR4A2) is linked to differentiation/development, homeostasis, and cellular metabolism. However, the role and molecular mechanism(s) of Notch1/NICD- NR4A2 axis in HNSCC pathogenesis are still unknown and need to be investigated. Methods: The clinicopathologic importance of Notch1 and NR4A2 was investigated using HNSCC patient samples and publicly available databases. NR4A2 was stably knocked out (KO) and Notch1 signaling was blocked using small-molecule inhibitor (PF3084014) in HNSCC cell lines and analyzed for tumorigenic and metastatic potential. We also examined the whole-genome NR4A2 target genes using ChIP sequencing. Results: Both Notch1 and NR4A2 were highly overexpressed in HNSCC patients. Inhibition of Notch1 signaling or NR4A2 KO significantly decreased the clonogenicity and migratory potential of HNSCC cells. Our ChIP analysis revealed that NR4A2 regulates genes involved in metabolism, hypoxia, cell cycle progression, integrin and Wnt signaling. Interestingly, we observed that NR4A2 regulates stem cell markers including Sox2, Nanog, and CD44 and their expression was drastically reduced upon Notch 1 inhibition. Conclusion: Targeting Notch1-NR4A2 signaling axis may be crucial for inhibition of cancer stem cell-mediated HNSCC pathogenesis. Citation Format: Sanjib Chaudhary, Ramesh Pothuraju, Zafar Sayed, Dwight T. Jones, Surinder K. Batra, Muzafar A. Macha. Deregulation of NOTCH 1/NR4A2 signaling axis in head and neck cancer pathogenesis [abstract]. In: Proceedings of the AACR-AHNS Head and Neck Cancer Conference: Optimizing Survival and Quality of Life through Basic, Clinical, and Translational Research; 2019 Apr 29-30; Austin, TX. Philadelphia (PA): AACR; Clin Cancer Res 2020;26(12_Suppl_2):Abstract nr A31.

Head and neck squamous cell carcinoma (HNSCC) is the sixth most common cancer, with high morbidity and mortality. Racial disparity in HNSCC is observed between African Americans (AAs) and whites, effecting both overall and 5-year survival, with worse prognosis for AAs. In addition to socio-economic status and demographic factors, many epidemiological studies have also identified factors including coexisting human papillomavirus (HPV) infection, primary tumor location, and a variety of somatic mutations that contribute to the prognostic incongruities in HNSCC patients among AAs and whites. Recent research also suggests HPV-induced dysregulation of tumor metabolism and immune microenvironment as the major regulators of HNSCC patient prognosis. Outcomes of several preclinical and clinical studies on targeted therapeutics warrant the need to elucidate the inherent mechanistic and population-based disparities underlying patient responses. This review systematically reports the underlying reasons for inconsistency in disease prognosis and therapy responses among HNSCC patients from different racial populations. The focus of this review is twofold: aside from discussing the causes of racial disparity, we also seek to identify the consequences of such disparity in terms of HPV infection and its associated mutational, metabolic, and immune landscapes. Considering the clinical impact of differential patient outcomes among AA and white populations, understanding the underlying cause of this disparity may pave the way for novel precision therapy for HNSCC.

Objectives/Hypothesis To study the complication rates of skin overgrowth, infection, and the need for revision surgery in longer length Baha™ abutments. Study Design Prospective observational cohort study compared with a retrospective historical control. Methods After the University of Nebraska Medical Center (UNMC) Institutional Review Board approval was obtained, data was collected from a prospective 8.5-mm abutment study group of 21 subjects with informed consent from October 2011 through October 2012, and was compared to a retrospective 5.5-mm abutment historical cohort of 23 patients who had undergone Baha™ by the same surgeon from May 2010 to October 2011. Patient demographics, body mass index (BMI), smoking status, and wound complications (skin overgrowth, infection, the need for revision surgery) were statistically investigated and compared between the groups. Results Forty-four patients were studied. The groups were similar in smoking status, diabetes, and a female preponderance. The 8.5-mm abutment group was older (P = 0.012). The average BMI for both groups was classified as overweight and nearly obese (BMI 28.8). Rates of infection, skin overgrowth, and the need for revision surgery related to wound complications were significantly decreased in the longer 8.5-mm abutment group (P = 0.020, P = 0.012, P = 0.007, respectively). BMI did not correlate with decreased infection, skin overgrowth, and the need for revision surgery based on abutment length as hypothesized (P = 0.214, P = 0.206, P = 0.408). Conclusions The 8.5-mm abutment lends to decreased complications postoperatively, including infection, skin overgrowth, and the need for revision surgery. Level of Evidence 3b. Laryngoscope, 124:989–992, 2014

Objective To assess the efficacy and safety of endoscopic management of subglottic stenosis both as a primary and as an adjunctive treatment in the pediatric population. Methods Retrospective review of pediatric patients with subglottic stenosis undergoing endoscopic airway procedures at a tertiary care pediatric medical center. Outcomes were assessed by systematic review to determine the success and failure of the endoscopic approach. Results Forty patients (22 male, 18 female) underwent endoscopic interventions for a diagnosis of subglottic airway stenosis between 2003 and 2006. Age ranged from 22 days old to 20 years old. Recorded degree of subglottic stenosis ranged from 10% to 99%. Fifty-three percent (21/40) had a history of prematurity, and 40% (16/40) had secondary airway diagnoses. Twenty-four patients underwent an endoscopic intervention initially (including laser or dilation, with or without topical mitomycin treatment), including four patients who underwent tracheostomy prior to the first endoscopic intervention. Sixteen underwent laryngotracheoplasty initially, including ten patients who underwent tracheostomy prior to the laryngotracheoplasty. Endoscopic treatment resulted in resolution of symptoms, and/or decannulation, and no further need for an open procedure in 58% of patients. Of the 24 patients undergoing endoscopic interventions initially, 14 patients underwent two or more endoscopic interventions, and 10 patients subsequently required tracheostomy or laryngotracheoplasty. When endoscopic procedures were used as an adjunct to laryngotracheoplasty, 60% (12/20) had resolution of symptoms, underwent decannulation, and did not require tracheostomy or revision laryngotracheoplasty. Conclusions The endoscopic approach can be successful in the management of properly selected patients with subglottic stenosis, either as the initial treatment modality or as an adjunctive treatment in cases of re-stenosis after open airway surgery. The likelihood of success with a minimally invasive procedure as the primary treatment decreases with worsening initial grade of subglottic stenosis.

BACKGROUND: The true rate of neurologic sequelae and infection from penetrating palatal trauma in children is unknown, which leads to significant variation in testing and treatment. OBJECTIVES: To (1) determine the incidence of stroke and infection in well-appearing children with penetrating palatal trauma and (2) describe patterns of testing and treatment for uncomplicated palatal trauma. METHODS: We assembled a retrospective cohort of children aged 9 months to 18 years with palatal trauma seen in the emergency department (ED) at a tertiary care pediatric hospital. Patients met the following definition: well-appearing with normal neurologic examination and a palate laceration but no findings requiring immediate operative care. Stroke was defined as any abnormal neurologic examination secondary to palatal trauma. Infection was defined as cellulitis or abscess secondary to palatal injury. All abnormal computed tomographic angiography (CTA) findings, except for free air, were considered positive and potentially significant. RESULTS: We identified 1656 potential subjects. A total of 995 of 1656 subjects were screened, and 205 of 995 met the case definition. A total of 122 of 205 had follow-up through at least 1 week after injury. The incidence of stroke in our study population was 0% (95% confidence interval [CI]: 0–2.5). One of 116 patients developed infection, for an incidence of 0.9% (95% CI: 0–5.3). A total of 90 of 205 (44%) subjects had CTA scans; the results of 9 (10%) were positive. No patients with positive CTA findings required operative care. No patients received anticoagulant medications. CONCLUSIONS: The incidence of morbidity from penetrating palatal trauma in the well-appearing child is extremely low. Diagnostic evaluation in the ED did not prompt clinical interventions other than antibiotics.

To identify clinical, audiological, and vestibular characteristics of posterior semicircular canal dehiscence.Retrospective case review.Tertiary referral center.Twelve patients aged 2 to 67 years identified with posterior semicircular canal dehiscence.Patients identified by suspicious clinical history and examination, confirmed by high-resolution computed tomography. Audiological evaluation included air and bone audiometry, tympanometry, acoustic reflexes, and vestibular evoked myogenic potential testing.Hearing loss was mixed in 9 patients, conductive in 2 patients, and sensorineural in 1 patient, with downward-sloping configuration being the most common. Imaging revealed that 7 of 12 patients had dehiscence into a high-riding jugular bulb and 1 patient had an enlarged vestibular aqueduct with a Mondini malformation. One patient had Apert syndrome and another patient had microtia/atresia. Vestibular symptoms were more common in the adult patients than in the pediatric patients, with chronic disequilibrium the most common complaint. Vestibular evoked myogenic potential testing confirmed dehiscence with the characteristic response of reduced threshold and higher amplitude compared with healthy patients.This is the first reported series of adult and pediatric patients with symptomatic posterior semicircular canal dehiscence. Posterior semicircular canal dehiscence represents a third-window lesion manifesting as hearing loss with vestibular dysfunction. Computed tomography findings of a dehiscent posterior canal can be verified with increased vestibular evoked myogenic potential responses as in other third-window lesions. Patients found to have a high-riding jugular bulb and hearing loss should have specific inspection of the posterior canal to ensure it is not dehiscent.

Objective Determine if passive smoke exposure (PSE) increases airway complications during outpatient mask anesthesia procedures in children. Methods A prospective cohort of children who underwent surgical procedures under mask anesthesia was studied with the American Thoracic Society children’s questionnaire on environmental and respiratory factors. Double-blinded outcomes with respect to adverse airway events were recorded both intraoperatively and in the recovery room for patients with and without passive smoke exposure. Multivariate comparisons assessing the likelihood of these airway complications were conducted between the PSE and nonexposed groups. Results Of 405 children, 168 (41.5%) had PSE. The incidence of airway complications during anesthesia or postanesthetic recovery was higher for all outcome measures for PSE children (all P ≤ 0.005), except for recovery room breath holding ( P = 0.086). Intraoperative laryngospasm and airway obstruction were 4.9 and 2.8 times more likely with PSE, respectively. Conclusions PSE significantly increases the risk of anesthesia-related airway complications during outpatient pediatric procedures. EBM rating: A-1b

Objective: To identify the most common otolaryngologic causes of mortality in the 0 to 19 age group in the state of Massachusetts and to estimate the pediatric otolaryngologic mortality rate based on population data. Study Design: Population-based retrospective cohort study. Methods: The Massachusetts State Registry of Vital Records and Statistics electronic database was searched for all otolaryngology related causes of death from 1990 to 2002 for children aged 0 to 19. The individual death certificates were then reviewed, and a database of otolaryngology related pediatric deaths was created. Results: A total of 59 otolaryngology related deaths were identified in the pediatric population from 1990 to 2002. Eighty-one percent of deaths occurred because of airway compromise caused by infection, anatomic obstruction, or congenital anomaly. The remaining 19% of deaths occurred because of aspiration, nonairway infections, and malignant neoplasms. Ninety-five percent of deaths in the children under age 10 were caused by airway compromise. Six of seven deaths (86%) in the age 15 to 19 group occurred because of malignant neoplasms. The overall mortality rate caused by otolaryngologic causes was estimated to be 0.28 per 100,000 population. Conclusions: The overall mortality rate for otolaryngology related deaths is low in the pediatric population. The vast majority of deaths are caused by airway compromise, primarily because of laryngotracheobronchitis or other upper airway obstruction. In older children (ages 15–19), malignant head and neck neoplasms are the leading cause of otolaryngology related deaths.

Objectives. To endeavor to explain why some graduates of extracorporeal membrane oxygenation (ECMO) therapy develop sensorineural hearing loss (SNHL) whereas others do not, to study the variability seen in the degree of SNHL, to attempt to explain why some graduates with SNHL experience progressive worsening whereas others do not, and to describe the time course of the onset of SNHL on the basis of identified risk factors.Design. A retrospective chart review with proportional-hazards regression analysis to identify specific risk factors for SNHL from a list of patient and treatment variables.Setting. Children’s Hospital Boston, a pediatric tertiary-care facility and ECMO center.Patients. Neonatal ECMO graduates born in 1986–1994 who survived to discharge and underwent audiologic evaluations (n = 111) and a random sample of ECMO graduates who survived to discharge and did not undergo audiologic evaluations (n = 30).Outcome Measures. Audiologic data, including the presence or absence of SNHL, the severity of SNHL at the most recent evaluation, the stability or progressive worsening of hearing (with the first evaluation compared with the most recent evaluation), and the occurrence of delayed-onset SNHL.Results. Twenty-nine (26%) of 111 ECMO graduates who underwent audiologic testing had SNHL at the last evaluation. Of these 29 subjects with SNHL, 21 (72%) had progressive SNHL, of whom 14 (48%) had delayed-onset SNHL. The age of identification of SNHL ranged from 4 months to 8 years 11 months. Factors identified with proportional-hazards regression analyses as being associated significantly with the time to onset of SNHL were a primary diagnosis of congenital diaphragmatic hernia (hazard ratio: 2.60), length of ECMO therapy (hazard ratio: 7.18), and number of days children received aminoglycoside antibiotics (hazard ratio: 5.56). Kaplan-Meier “time-to-event” curves were constructed to illustrate the time course of onset of SNHL, as affected by each of the variables identified as significant risk factors.Conclusions. These findings illustrate the need for early, routine, audiologic evaluations throughout childhood for all ECMO graduates. Children at even greater risk for developing SNHL because of a history of congenital diaphragmatic hernia, prolonged ECMO therapy, and/or a lengthy course of aminoglycoside antibiotic therapy should be monitored even more closely throughout childhood, depending on the child’s individual risk indicators, as suggested here. On the basis of these risk indicators, efforts can be made to minimize the risk of hearing loss while a child is being treated with ECMO. In addition, these risk indicators can assist with counseling families of ECMO graduates regarding the child’s specific risk of developing SNHL and how it can be managed should it occur.

Objective To describe the epidemiology, natural history, and treatment of epiglottitis in the Hemophilus influenzae type B (Hib) vaccine era. Design Ten-year retrospective study. Setting Tertiary-care children's hospital. Patients Nineteen patients with a discharge diagnosis of epiglottitis. Intervention As indicated by the presentation of the patient, including direct laryngoscopy, intubation, intravenous antibiotics, and steroids. Main outcome measures Presentation, management, and microbiology. Results Presenting symptoms included fever, drooling, and hot potato voice. Patients' ages ranged from 15.8 months to 17.5 (mean 8.9) years. From 1992 to 1997, the mean age was 5.8 years; from 1998 to 2002, the mean age was 11.6 years. Sixty-eight percent of patients were transferred from an outside hospital. A lateral neck radiograph was recorded in 84% of patients. Mean leukocyte count was 16,600. Direct laryngoscopy with intubation was performed in 79%; intubation was for an average of 3.5 days. H. influenzae was cultured in six patients, five of which had up-to-date immunizations. The most commonly administered antibiotics were ampicillin/sulbactam and ceftriaxone. Steroids were administered to 63% of patients. Complications included deep neck space infection (2), seizure (1), recurrent illness (1), and vocal granuloma (1). There were no deaths. Conclusion The demographics, causative organisms, and natural history of epiglottitis have changed substantially in the Hib vaccination era. The clinician evaluating and treating patients with epiglottitis should be aware of current trends.

Adenotonsillectomy (AT) is commonly performed for childhood OSA syndrome (OSAS), but little is known about prognosis without treatment.The Childhood Adenotonsillectomy Trial (CHAT) randomized 50% of eligible children with OSAS to a control arm (watchful waiting), with 7-month follow-up symptom inventories, physical examinations, and polysomnography. Polysomnographic and symptomatic resolution were defined respectively by an apnea/hypopnea index (AHI)2 and obstructive apnea index (OAI)1 and by an OSAS symptom score (Pediatric Sleep Questionnaire [PSQ])0.33 with ≥ 25% improvement from baseline.After 194 children aged 5 to 9 years underwent 7 months of watchful waiting, 82 (42%) no longer met polysomnographic criteria for OSAS. Baseline predictors of resolution included lower AHI, better oxygen saturation, smaller waist circumference or percentile, higher-positioned soft palate, smaller neck circumference, and non-black race (each P.05). Among these, the independent predictors were lower AHI and waist circumference percentile90%. Among 167 children with baseline PSQ scores ≥ 0.33, only 25 (15%) experienced symptomatic resolution. Baseline predictors were low PSQ and PSQ snoring subscale scores; absence of habitual snoring, loud snoring, observed apneas, or a household smoker; higher quality of life; fewer attention-deficit/hyperactivity disorder symptoms; and female sex. Only lower PSQ and snoring scores were independent predictors.Many candidates for AT no longer have OSAS on polysomnography after 7 months of watchful waiting, whereas meaningful improvement in symptoms is not common. In practice, a baseline low AHI and normal waist circumference, or low PSQ and snoring score, may help identify an opportunity to avoid AT.ClinicalTrials.gov; No.: NCT00560859; URL: www.clinicaltrials.gov.

BACKGROUND AND OBJECTIVES: Polysomnography defines the pathophysiology of obstructive sleep apnea syndrome (OSAS) but does not predict some important comorbidities or their response to adenotonsillectomy. We assessed whether OSAS symptoms, as reflected on the Sleep-Related Breathing Disorders Scale of the Pediatric Sleep Questionnaire (PSQ), may offer clinical predictive value. METHODS: Baseline and 7-month follow-up data were analyzed from 185 participants (aged 5–9 years with polysomnographically confirmed OSAS) in the surgical treatment arm of the multicenter Childhood Adenotonsillectomy Trial. Associations were assessed between baseline PSQ or polysomnographic data and baseline morbidity (executive dysfunction, behavior, quality of life, sleepiness) or postsurgical improvement. RESULTS: At baseline, each 1-SD increase in baseline PSQ score was associated with an adjusted odds ratio that was ∼3 to 4 times higher for behavioral morbidity, 2 times higher for reduced global quality of life, 6 times higher for reduced disease-specific quality of life, and 2 times higher for sleepiness. Higher baseline PSQ scores (greater symptom burden) also predicted postsurgical improvement in parent ratings of executive functioning, behavior, quality of life, and sleepiness. In contrast, baseline polysomnographic data did not independently predict these morbidities or their postsurgical improvement. Neither PSQ nor polysomnographic data were associated with objectively assessed executive dysfunction or improvement at follow-up. CONCLUSIONS: PSQ symptom items, in contrast to polysomnographic results, reflect subjective measures of OSAS-related impairment of behavior, quality of life, and sleepiness and predict their improvement after adenotonsillectomy. Although objective polysomnography is needed to diagnose OSAS, the symptoms obtained during an office visit can offer adjunctive insight into important comorbidities and likely surgical responses.

The management of a mastoid subperiosteal abscess has traditionally required mastoidectomy. With the improvement of antibiotic therapy current literature supports the treatment of uncomplicated acute mastoiditis with myringotomy and intravenous antibiotics. Treatment of a mastoid subperiosteal abscess with tympanostomy tube insertion, intravenous antibiotics, and postauricular incision and drainage of the abscess avoids the morbidity and potential complications of mastoid surgery in young children. Three patients diagnosed with a mastoid subperiosteal abscess were managed in this way. The outcome of their treatment has been documented with lengthy otologic follow-up. Complete resolution of the acute infectious process was achieved in all cases with no evidence of recurrent disease.

Objective: To examine the effects of endoscopic sinus surgery on the pulmonary status of cystic fibrosis (CF) patients through the objective parameters of steroid use, pulmonary function tests (PFTs), and inpatient hospital days (IHDs). Methods: Retrospective chart review of all patients with CF who underwent endoscopic sinus surgery from 1993 to 1999 at a tertiary care children's hospital. Preoperative pulmonary function, inhaler and steroid use, and IHDs were compared to postoperative parameters within a 1-year period. Results: Sixty-six patients, including eight lung transplant patients, underwent a total of 112 endoscopic sinus surgery procedures; 25 patients underwent more than one procedure. Patients were taking oral steroids preoperatively in 28% of procedures and inhaled steroids in 40%. Postoperatively, there was no statistically significant change in oral or inhaled steroid use, or in postoperative pulmonary function. If the index hospitalization, which was often for reasons not related to sinus disease, was considered part of the preoperative time period, endoscopic sinus surgery (ESS) was noted to result in a marked reduction (9.5 days (adjusted), P =0.001) in hospital days during the subsequent 6 months. If the date of the procedure alone was used to define pre- and postoperative time periods, the reduction in postoperative days was more modest and not statistically significant (3.5 days (adjusted), P =0.21). Conclusions: Although we found no statistically significant difference in PFTs, or steroid requirements following ESS, ESS may have resulted in a reduced need for hospitalization in the 6 months following the procedure. Future prospective studies in a larger number of patients and using more detailed outcome measures are needed to better evaluate the effects of endoscopic sinus surgery in pediatric patients with CF.

Background: Persistent nasolacrimal duct obstruction (NLDO) often requires treatment by probing, intubation, or balloon dacryoplasty. Refractory cases have been managed by external dacryocystorhinostomy (DCR), which leaves a scar; however, this procedure is generally avoided in young children. Endoscopic DCR has been successfully performed in adults and described in children. We report the success of this procedure in a series of pediatric patients. Methods: A retrospective review of all endoscopic lacrimal procedures performed in a 3-year period was undertaken. Seventeen children (22 ducts) with persistent NLDO after at least one failed probing, with or without silicone tube placement, underwent endoscopic DCR. Follow-up ranged from 6 to 36 months, and success was defined as resolution of tearing and discharge by follow-up clinical evaluation and by parental history. Results: All but 2 patients (88%) with NLDO showed complete resolution of tearing and discharge. These 2 patients had recurrent symptoms after the Crawford tubes were removed and required revision endoscopic DCR. No complications from this procedure were noted. Conclusions: Endoscopic DCR is a safe and effective means of treating persistent NLDO in infants and young children when simple probing, intubation, or balloon procedures have failed. The team ophthalmology-otolaryngology endoscopic approach provides a highly successful alternative for patients with a persistent distal obstruction that might otherwise require an external procedure. (J AAPOS 2001;5:143-7)

Two studies have reported that young women with breast cancer face increased risk of early mortality if their first child was male rather than female. An immunological mechanism has been suggested. We sought to confirm these results in a larger, historical cohort study of 223 parous women who were aged45 years at breast cancer diagnosis during 1983-1987. Subjects were identified through the Maine Cancer Registry. Follow-up data were obtained from hospitals, physicians, and death certificates. Reproductive history data were obtained from the next of kin of the deceased women, birth certificates, physicians, hospitals, and lastly, subjects. With a 7-year follow-up, multivariate modeling found a lower mortality risk in women with a male first child (hazard ratio [HR] 0.51, 95% confidence interval [CI] 0.32-0.81, log-rank comparison). The survival advantage remained for at least 13 years in women with a male firstborn. Thus, previous studies were not confirmed. Mortality risk in young women with breast cancer is not increased by having borne a male first child rather than a female first child.

From 1982 to 1984, the authors conducted a population-based case-control study of lung cancer in men and women nonsmokers in New York State. In-person interviews were completed for 437 lung cancer cases (197 never smokers, 240 former smokers) and 437 matched population controls. Cases and controls were asked to report any history of physician-diagnosed nonmalignant lung disease; cases were more likely than controls to report such a history. Statistically significant associations were found for emphysema (odds ratio (OR) = 1.94, 95% confidence interval (CI) 1.10-3.43), chronic bronchitis (OR = 1.73, 95% CI 1.10-2.72), and the combined endpoint of emphysema, chronic bronchitis, or asthma (OR = 1.82, 95% CI 1.26-2.63). After adjustment for active and passive tobacco smoke exposure, emphysema, chronic bronchitis, and asthma (each condition and the combined endpoint) were significantly associated with lung cancer risk. The risk was more marked for squamous cell carcinomas and for subjects who were diagnosed at older ages, and it remained significant when surrogate interviews were excluded. These results are consistent with the hypothesis that certain prior lung conditions increase the risk of lung cancer in men and women nonsmokers.

Background: The International (formerly National) Bariatric Surgery Registry began collecting data in January 1986. The aim of this study was to examine changes in the practice of surgical treatment of severe obesity that occurred during the decade of 1986 through 1995, as observed in the IBSR data. Methods: All data submitted to the IBSR during the decade were transferred to the IBM mainframe computer for analysis. Characteristics of operative type populations were compared over time using analysis of variance (ANOVA) for age, body mass index (BMI), operative weight and Chi-square (χ2) test for gender. Results: There has been a steady increase over the decade in mean patient weight. The operations used have changed from predominantly ‘simple’ operations to more frequent use of ‘complex’ operations. Within the categories of ‘simple’ and ‘complex’, an increase in the variety of operations occurred. As a group, patients with ‘simple’ operations have been heavier, more often male and public pay patients than those who have undergone ‘complex’ operations. One year weight loss was greater for Roux-en-Y gastric bypass (RGB) than vertical banded gastroplasty (VBG), but follow-up rates were too low to study the relative merits of the operations used. The reported incidence of operative mortality and serious complications (leak with peritonitis, abscess and pulmonary embolism) remained low. Conclusions: These observations and their implications can be summarized in three statements which relate to action for improved patient care in the beginning of the new century: (1) increasing weight of candidates for surgical treatment during this decade indicates the need for earlier use of operative treatment before irreversible complications of obesity can develop; (2) low risk of obesity surgery, decreasing postoperative hospital stay, and early weight control support the continued and increased use of surgical treatment; (3) continued widespread use of both ‘simple’ and ‘complex’ operations with increased modifications of standard RGB and VBG procedures emphasizes the need for standardized long-term data and analyses regarding both weight control and postoperative side-effects.

Among congenital neck masses seen in the pediatric population, thyroglossal duct cysts are the most common. This chapter will explore the cyst’s underlying embryologic pathogenesis from a persistent thyroglossal tract and why the lesion presents in a typical midline position. Additional sections are dedicated to epidemiology, pertinent history, physical exam findings, and differential diagnosis. Successful management of thyroglossal lesions requires imaging, preferably ultrasonography, to document the presence of a functioning thyroid gland, and excision of the cyst using the Sistrunk procedure. Strategies for dealing with a recurrent or infected cyst are also included.

BACKGROUND In the 1980s, prostate specific antigen (PSA) came into wide use as a prostate carcinoma screening and detection method in the United States. Following the introduction of PSA, the age-adjusted incidence of prostate carcinoma reported by the Surveillance, Epidemiology, and End Results (SEER) program in the United States rose rapidly (from 84.4/100,000 in 1984 to 163/100,000 in 1991). When an increase in incidence is observed following the introduction of a screening method, a subsequent decrease in incidence may be expected as prevalent cases are removed from the population (a cull effect). Incidence rates may also fall due to factors such as decreased intensity of screening. The Utah Cancer Registry data were examined for a decrease in prostate cancer incidence. METHODS We tracked age-adjusted prostate carcinoma incidence trends from the population-based Utah Cancer Registry and compared them with rates from the SEER national registry. RESULTS A rapid and highly correlated rise in prostate carcinoma incidence has been observed in both SEER and Utah incidence rates between 1988 and 1991, the last year for which SEER data are available. In 1992, Utah incidence rates peaked at 236.2 per 100,000. In 1993 and 1994, Utah incidence rates fell to 195.0, and an estimated 164.0 per 100,000, respectively. CONCLUSIONS Population-based data from the Utah Cancer Registry indicates that the incidence of prostate carcinoma is decreasing rapidly after a similarly rapid increase. Cancer 1996;77:1342-8.

OBJECTIVES. Each case of a continuous series of invasive cervical cancer cases was studied with a structured review procedure conducted by an expert panel to assess the reason that it was not detected before it became invasive. METHODS. All cases of invasive cervical cancer diagnosed in a 5-year period among Connecticut residents were identified; a screening history and screening outcome were obtained for 72% (481 of 664). RESULTS. Two hundred fifty women (51.9%) had suboptimal screening. One hundred thirty-seven women (28.5%) had never had a screening test, and their mean age was greater than that of the rest of the study population (64.5 years vs 46.5 years). Of the 344 women who had ever had a Pap test, 113 (32.8%) had their last Pap test 5 or more years before their diagnosis of invasive cancer; 52 (15.1%) were not followed up properly; 33 (9.6%) had their last smear misread as normal; and 118 (34.3%) developed cervical cancer within 3 years of their last Pap test. CONCLUSIONS. Physicians, nurses, and other care providers need to ensure that woman have timely and accurate screening with proper follow-up, make increased efforts to reach older women, and improve quality control of Pap smear readings.

M IN IS E M IN A R S stapedectomies in the past were undoubtedly performed on ears with occult third window syndromes. We will present a review of superior SCD and other third window syndromes, with an emphasis on differentiating them from more common otologic diagnoses. Cases will be presented that illustrate how these syndromes should be included in the differential diagnosis of many common otologic presentations. SCD, the most common third window syndrome, will be discussed in detail, including diagnosis and treatment indications, options, and outcomes.

Objectives/Hypothesis Penetrating palatal trauma in children presents a diagnostic dilemma regarding the small but severe risk of injury to carotid vessels. Decisions regarding which children require computed tomography with angiography must be balanced against the risk of radiation-induced malignancy. Our objectives were to compare outcomes between children with and without computed tomography with angiography in the evaluation of palatal trauma and to identify thresholds where the ideal strategy changes in the management of children with palatal trauma through sensitivity analyses. Study Design Decision analytic techniques were used to compare management strategies for penetrating palatal trauma. Methods We assigned utilities to the following outcomes: 1) perfect health, 2) future malignancy, 3) carotid injury diagnosed by computed tomography with angiography, and 4) delayed diagnosis of stroke. We calculated outcomes when the risk of stroke ranged from 0.01% to 5.0% for a hypothetical cohort of 10,000 injured children. Results Not obtaining computed tomography with angiography is the optimal strategy when the stroke risk is less than 4.5%. In two-way sensitivity analyses that consider a range of probabilities of radiation-induced malignancy and stroke, not obtaining computed tomography with angiography on all patients dominates as a strategy until the risk of stroke exceeds 2.3%, and the risk of malignancy is under 0.24%. Routine imaging would introduce 20 additional malignancies for each additional stroke diagnosed. Conclusions Routine use of computed tomography with angiography for well-appearing children with palatal trauma should be reconsidered, as the risk of radiation-induced malignancy may outweigh the benefit of identifying the rare carotid injury. Level of Evidence 2b.

The immunodeficient child presents a unique challenge to the otolaryngologist, who must be able to recognize the early stages of immunodeficiency as well as be a consultant in later stages of the disease. Infection by HIV has brought about a new era both in the magnitude of immunodeficiency seen and in our understanding of the mechanisms of immune function. The current literature concerning HIV-infected children with manifestations in the head and neck is reviewed. Many similarities between HIV-infected children and other immunosuppressed patients have emerged, and salient features of immunodeficiency diseases of childhood are examined.

The relationship between patella alta and patellar subluxation may, in part, reflect the relationship between the height of the patella above the tibiofemoral joint line and the patellofemoral contact force. This study reports on the direct in vitro measurement of the patellofemoral contact force, and its point of application on the patella, as a function of patellar height. The contact force was measured by a specially designed six-degree-of-freedom force transducer under loading simulating rising from a chair. The magnitude of the resultant contact force increased significantly with superior displacement of the patella. The magnitude of the resultant contact force changed as much as 3% per millimeter of change in patellar height. The details of this response varied among the knees tested and depended on the original anatomical patellar height. For a high-riding patella, the onset of tendofemoral contact is delayed and the magnitude of the patellofemoral contact continues to increase with increasing flexion angle. Early onset of tendofemoral contact associated with a low-riding patella results in a concomitant reduction in the magnitude of the contact force. The medially directed component of the contact force acting on the patella resists lateral subluxation of the patella. This force component increased with superior displacement of the patella. This may explain in part the tendency for a high-riding patella to sublux. For all seven specimens tested the point of application of the resultant contact force migrated superiorly with inferior displacement of the patella.

BACKGROUND Approximately 15% of all lung cancer deaths in the United States (about 22,350 deaths annually) may not be directly attributable to active cigarette smoking. Consumption of beta carotene, which is derived almost exclusively from intake of fruits and vegetables, has been associated with a reduced risk of lung cancer in smokers. However, studies examining this association in nonsmokers, particularly nonsmoking men, are limited. PURPOSE The purpose of this study was to examine whether dietary factors including beta carotene and retinol are associated with a reduced risk for lung cancer in nonsmoking men and women. METHODS A population-based, matched case-control study of lung cancer in nonsmokers was conducted in New York State from 1982 to 1985. Dietary interviews were completed for 413 individually matched case-control pairs of subjects. To determine whether the relationship between dietary intake from specific food groups and lung cancer differed by type of interview, smoking history, sex, age, or histologic type, we examined data on the case-control pairs from each subgroup separately. The intake of beta carotene and retinol was calculated as the weighted sum of the monthly frequencies of consumption of food items containing these nutrients, where the weights correspond to the nutrient content of a typical portion of the food items. RESULTS Consumption of greens (P for trend < .01), fresh fruits (P for trend < .01), and cheese (P for trend < .05) was associated with a significant dose-dependent reduction in risk for lung cancer, whereas consumption of whole milk (P for trend < .01) was associated with a significant dose-dependent increase in risk. Use of vitamin E supplements was also protective (odds ratio = 0.55; 95% confidence interval [CI] = 0.35-0.85). Increased consumption of the following food groups was associated with a reduction in risk among females: vegetables (P for trend < .025), raw fruits and vegetables (P for trend < .005), and dairy products (P for trend < .025). In males, increased consumption of raw fruits and vegetables was associated with a reduced risk for lung cancer (P for trend < .005). Dietary beta carotene (OR = 0.70; 95% CI = 0.50-0.99), but not retinol (OR = 0.98; 95% CI = 0.82-1.17), was significantly associated with risk reduction. CONCLUSIONS This is the largest study to date of dietary factors and lung cancer in nonsmokers; results suggest that dietary beta carotene, raw fruits and vegetables, and vitamin E supplements reduce the risk of lung cancer in nonsmoking men and women.

Hemangioma is a well-recognized cause of airway obstruction in the infant with stridor. Corticosteroid and laser therapy are effective in stabilizing the airway in most cases. There are, however, some extensive airway lesions that are not adequately managed by these modalities. This report describes the use of recombinant interferon alfa-2a in 15 patients with life-threatening airway hemangiomas. All patients had failed corticosteroid and/or laser therapy. Multiple upper airway sites were involved, including the base of the tongue, supraglottis, subglottis, trachea, and mediastinum. Eleven patients have completed therapy and are doing well. Four patients have resolving lesions on the drug regimen. Life-threatening airway lesions unresponsive to conventional treatment should be considered for a trial of interferon alfa-2a.

We examined the relationship between the survival of women with breast cancer and the gender of their first children using a genealogy-based survival analysis. The study group consisted of 2,155 parous women diagnosed in Utah (United States) with first primary breast cancers (excludingin situ tumors). We calculated hazard rate ratios (HRR) which were adjusted for stage, median survival times, and proportions surviving for three-, five-, and 10-year intervals stratified by age at diagnosis. Median survival among women diagnosed under the age of 45 was 171 months if the first child was female, but only 66 months if the first child was male (HRR=1.66, 95 percent confidence interval=1.07–2.57, for male children). For women diagnosed at age 45 or older, all survival times were similar, although women whose first child was male had slightly longer median survival time. These findings suggest that the gender of the first child has a strong influence on survival among women diagnosed under 45 years of age, but not among those diagnosed later in life. Gender of the first offspring may be a useful clinical indicator of prognosis and survival and may provide insights into etiologic and promotional factors for breast cancer.Cancer Causes and Control 1994, 5, 26–30.

Objectives To review the characteristic microbiology of the paranasal sinuses in patients with cystic fibrosis who undergo endoscopic sinus surgery. To examine the subtypes of organisms cultured from the maxillary sinuses and determine their sensitivity to antibiotic therapy. Study design Retrospective chart review. Setting Tertiary care children's hospital. Methods Sinus cultures were obtained from 51 patients with cystic fibrosis during endoscopic sinus procedures between 2000 and 2004 at a tertiary care children's hospital. A retrospective chart review was undertaken to obtain culture and sensitivity data of the sinus contents. Results The most common bacteria isolated was Staphylococcus aureus (71%), followed by Pseudomonas aeruginosa (PSA) (27%), Haemophilus influenzae (21%), Staphylococcus non-aureus (16%) and Streptococcus viridans (12%). Streptococcus pneumoniae and Moraxella catarrhalis were rarely isolated (2% and 0% respectively). Twenty-nine percent of the patients with cultures positive for PSA were of the mucoid variant. Only one patient had culture positive Escherichia coli. Antibiotic resistance among the more common organisms cultured from the sinus samples is also listed. Conclusion Staph. aureus is the most common isolate in the sinuses of this pediatric CF population followed by P. aeruginosa and H. influenzae. Although many isolates are pansensitive, some isolates are panresistant.

Cerebrospinal fluid leaks can be difficult management problems. Little information has been published about handling these cases in the pediatric population. A review of cases over the past 10 years at Boston Children's Hospital was undertaken to identify any prognostic factors and therapeutic recommendations. Twenty-seven patients were identified. While most patients responded to conservative therapy, those with leaks that persisted longer than 8 days required some type of operative closure. Severity of injury had little correlation with the occurrence of a leak. The findings in this study indicate that most pediatric cases can be managed on a conservative basis.

Objective The use of image guidance for sinonasal and skull base surgery has been well-characterized in adults but there is limited information on the use of these systems in the pediatric population, despite their widespread use. The aim of this study is to evaluate the use of image guidance systems to facilitate an endoscopic minimally invasive approach to sinonasal and skull base surgery in a pediatric population. Methods A retrospective cohort study was performed at a tertiary pediatric hospital. Thirty-three children presented with complications of sinusitis, tumors, traumatic, or congenital lesions of the skull base and underwent endoscopic surgery using image guidance from March 2000 to April 2007. Patient variables including diagnosis, extent of disease, and complications were extracted from paper and computer charts. Additional surgical variables including set-up time, accuracy, surgeon satisfaction index and number of uses per case were also reviewed. Results Twenty-eight patients (85%) underwent sinonasal surgery and five (15%) underwent skull base surgery. Indications included infectious complications of acute sinusitis ( N = 15), neoplasms ( N = 12), choanal atresia ( N = 4), and cerebrospinal fluid leak ( N = 2). Thirty-one patients (94%) required only one procedure. No surgical complications were reported. Surgeon satisfaction, mean accuracy and number of uses per procedure increased over time ( p Conclusions Image guidance systems are safe and effective tools that facilitate a minimally invasive approach to sinonasal and skull base surgery in children. Consistent with adult literature, usage and surgeon comfort increased with experience. The additional anatomical information obtained by image guidance systems facilitates a minimally invasive endoscopic approach for sinonasal and skull base pathologies.

To determine the prevalence of sensorineural hearing loss (SNHL) in cystic fibrosis (CF) patients and its relationship to antibiotic use.Case series with chart review.Tertiary care pediatric hospital.We reviewed the medical records of CF patients seen in our children's hospital between March 1994 and December 2007. Data collected included patient demographics, audiograms, tympanograms, genotype, and use of potentially ototoxic antibiotics.Seven of 50 (14%) patients had SNHL. Three percent of patients who receivedor=10 courses of intravenous aminoglycosides had SNHL versus 43 percent of those who received10 courses (P0.01). No patients who received five or fewer courses of nasal irrigation with aminoglycosides had SNHL versus 23 percent of those who received more than five courses (P0.05). Nine percent of patients who received five or fewer courses of macrolides had SNHL versus 60 percent of those who received more than five courses (P=0.079).CF patients receiving aminoglycosides are at high risk for developing SNHL.

Incidence rates and standardized incidence ratios (SIRs) for invasive and in situ cervical cancers diagnosed in 1982-87 were analyzed according to total population size of 148 towns, using data from the population-based Connecticut Tumor Registry. Previous studies have not considered socioeconomic or sociodemographic variables in analyzing cervical cancer rates in urban-rural or population density groups. In multiple regression analyses, increases in SIRs for invasive and in situ cancer from medium-sized to large towns were explained by differences in poverty prevalence or other socio-demographic variables. Nevertheless, cancer screening programs (aimed at preventing invasive cancer through early detection) could be targeted to some extent on the basis of town size category, because larger towns include large numbers of poorer and minority women with higher rates of invasive cervical cancer. SIRs for in situ cancer were significantly elevated in the largest towns (100,000 + total population), and primary prevention programs could target these larger towns with a higher prevalence of poverty.

Objective To assess the benefits of adenotonsillectomy in the treatment of pediatric patients with PFAPA (periodic fever, aphthous ulcers, pharyngitis, and adenitis) syndrome. Design Prospective case series. Setting Tertiary care pediatric hospital. Patients Pediatric patients meeting criteria for PFAPA syndrome. Intervention Tonsillectomy with or without adenoidectomy. Main Outcome Measure Resolution of PFAPA symptoms. Results Twenty-seven (14 female, 13 male) children with PFAPA syndrome underwent tonsillectomy with or without adenoidectomy from 2004 through 2006. The length of follow-up for all patients ranged from 8 to 41 months. A total of 26 patients experienced a complete resolution of their symptoms. The 1 child who continued to have febrile episodes had fever cycles that were not regular in duration or interval and in hindsight was not likely a patient with PFAPA syndrome. Conclusions Our findings showed complete resolution of symptoms in 26 of 27 patients with PFAPA syndrome treated surgically. Patients who meet clinical criteria for PFAPA syndrome should be considered for tonsillectomy and adenoidectomy if they do not respond to medical management.

Data from a large case-control study of breast cancer were examined to test the hypothesis that maternal age at the birth of female offspring is related to the incidence of breast cancer in daughters. Participants were between the ages of 20 and 54 at the time of the study. Based on results for 2,492 parous women who were newly diagnosed with breast cancer and 2,687 parous controls from the general population, a 15-year increase in maternal age was found to be associated with a 29% increase in the risk of breast cancer in daughters. Adjustment for the daughter's age, her own reproductive history, and other potential confounding factors yielded an estimate of 25% for this increase in risk (95% CI, 8% to 46%). The corresponding increase among 499 nulliparous cases and 457 nulliparous controls was 7%, which was not statistically significantly different in magnitude from the increase among parous women. These findings provide evidence for perinatal influences on the subsequent incidence of breast cancer during adulthood. Although specific mechanisms cannot be inferred directly, the results are consistent with the hypothesis that mutations in the genes of the human egg or sperm play a role in the etiology of breast cancer in female offspring.

Background Vocal cord dysfunction (VCD) is an increasingly recognized condition that affects the upper airway, which can be difficult to discriminate from asthma. Speech therapy and psychological cognitive therapy are the mainstays of treatment, but other modalities have been used when response is unsatisfactory. Objective To present 2 case studies in which VCD has been treated with long-term tracheostomy. Methods In the first patient, VCD was diagnosed by nasoendoscopic demonstration of paradoxical movement of the vocal cords. The patient was transferred to a regional unit, where nasoendoscopy was performed, which revealed immobile and adducted vocal cords. The decision to perform emergency surgical tracheostomy was made. In the second patient, a possible additional diagnosis of VCD was suggested during a hospital stay, and nasoendoscopy was performed. Results Both patients report considerable subjective benefits. Objective improvement was seen in only one patient. Conclusions Tracheostomy is an invasive procedure that carries risk of potential morbidity and should only be considered as a final option in carefully selected cases.

Context. Children frequently ingest coins. When lodged in the esophagus, the coin may cause complications and must either be removed or observed to pass spontaneously.Objectives. (1) To compare relatively immediate endoscopic removal to a period of observation followed by removal when necessary and (2) to evaluate the relationship between select clinical features and spontaneous passage.Design/Setting. Randomized, prospective study of children 24 hours earlier. Children were randomized to either endoscopic removal (surgery) or admission for observation, with repeat radiographs ∼16 hours after the initial image.Outcome Measures. Proportion of patients requiring endoscopic removal, length of hospital stay, and the number of complications observed.Results. Among 168 children who presented with esophageal coins lodged in the esophagus, 81 were eligible. Of those eligible, 60 enrolled, 20 refused consent, and 1 was not approached. In the observation group, 23 of 30 (77%) children required endoscopy compared with 21 of 30 (70%) in the surgical group. Total hospital length of stay was longer in the randomized-to-observation group compared with the randomized-to-surgery group (mean: 19.4 [SD: ±8.0] hours vs 10.7 [SD: ±7.1] hours, respectively). There were no complications in either group. Spontaneous passage occurred at similar rates in both groups (23% vs 30%). Spontaneous passage was more likely in older patients (66 vs 46 months) and male patients (odds ratio: 3.7; 95% confidence interval: 0.98–13.99) and more likely to occur when the coin was in the distal one third of the esophagus (56% vs 27% [95% confidence interval: 1.07–5.57]).Conclusions. Because 25% to 30% of esophageal coins in children will pass spontaneously without complications, treatment of these patients may reasonably include a period of observation, in the range of 8 to 16 hours, particularly among older children and those with distally located coins.

To determine the accuracy of computed tomography (CT) in the diagnosis of pediatric chronic rhinosinusitis (CRS).Multi-institutional prospective dual cohort study.Two cohorts of children undergoing CT of the paranasal sinuses were prospectively evaluated. The first cohort consisted of children undergoing CT in preparation for endoscopic sinus surgery (diseased group). The second cohort consisted of children undergoing CT for nonsinusitis reasons (nondiseased control group). Sinus CT scans were scored according to the Lund-MacKay system. Diagnostic accuracy was quantified with the receiver operating characteristic curve. Sensitivity, specificity, and predictive value analyses were conducted.A total of 66 pediatric patients (mean age, 8 years) were studied in the diseased group and exhibited a mean Lund score of 10.4 (95% confidence interval, 9.2-11.5); 192 control patients (mean age, 9 years) exhibited a mean Lund score of 2.8 (95% confidence interval, 2.4-3.2). The area under the curve for the receiver operating characteristic was 0.923 (P.001), indicating excellent diagnostic accuracy. Adopting a Lund score cutoff of 5 to represent true disease, the CT scan demonstrated a sensitivity and specificity of 86% and 85%, respectively. Lund scores of 2 or less have an excellent negative predictive value, whereas Lund scores of 5 or greater have an excellent positive predictive value (ie, strongly indicate true disease).The sinus CT scan demonstrates excellent diagnostic accuracy for the diagnosis of pediatric CRS, with excellent sensitivity and specificity. However, its predictive value depends substantially on the base rate prevalence of CRS in the population being evaluated.

Objective The purpose of this study was to investigate the association between deep dental overbite and eustachian tube dysfunction (ETD). Design Case-control study Setting Tertiary care pediatric otolaryngology outpatient clinic at the Children's Hospital, Boston, Massachusetts. Patients 105 patients between the ages of 2 and 6 years. Study Measurements Dental overbite, overjet, and occlusal relationships were measured by an observer who was unaware of ETD status. ETD was defined as having ventilation tubes in place or having the recommendation for ventilation tube placement by an attending pediatric otolaryngologist. In addition, demographic information and medical and social histories were prospectively recorded. Results In a multivariate logistic regression model, children with deep bites were 2.8 times more likely to have ETD than those without deep bites (P = .03). Other independent risk factors for ETD identified in this model were family history of otitis media (OM) and age less than 3 years. Conclusions Children with deep dental overbites are at a significantly increased risk for developing ETD.

The authors assessed body mass index (BMI), measured as Quetelet's index (weight in kilograms divided by the square of height in meters), in relation to lung cancer risk in never and former smokers by using data from a population-based, individually matched, case-control study conducted in New York State from 1982 to 1985. To be included in the study, subjects must never have smoked more than 100 cigarettes in their lifetime (never smokers) or not have smoked more than 100 cigarettes during the last 10 years (former smokers). Data on height and weight were complete for 412 of 439 case-control pairs. A positive relation was found between BMI and lung cancer risk for both never smokers (188 case-control pairs) and former smokers (224 pairs). When subjects were combined, those in the eighth (highest) octile (BMI > 30.84) had more than twice the odds of being cases compared with those in the lowest octile (BMI < or =21.26, 95 percent confidence interval: 1.2, 4.4). These study results are consistent with those from studies of BMI and other cancer sites but differ from lung cancer results usually found in predominantly smoking populations.

To evaluate the treatment, perioperative management, and outcome of infants who underwent repair of congenital tracheal stenosis. We hypothesized that early resection and tracheoplasty with early weaning of ventilatory support results in less mucosal injury, and thus better outcome.Retrospective study from 1986 to 1996.Tertiary care children's hospital.Seventeen consecutive infants with congenital tracheal stenosis, aged from birth to 16 months. Fifteen patients had complete tracheal rings, 6 of whom also had a left pulmonary artery sling. Fourteen patients underwent either tracheoplasty or resection and reanastomosis of the trachea, both facilitated by cardiopulmonary bypass.Six patients underwent resection and reanastomosis; 4 patients were extubated within 2 to 5 days without sequelae. There was 1 unrelated perioperative death. Two patients required reintubation. Eight patients required tracheoplasty due to severe tracheal stenosis and had variable postoperative courses. Seven of 14 patients required 0 to 1 postoperative bronchoscopies. Seven of 14 patients required 2 to 7 bronchoscopies for granulation tissue formation, cicatrix, graft collapse, and tracheitis. One patient required numerous procedures and revision tracheoplasty for cicatrix and stenosis.Correction of short-segment (5 rings) tracheal stenosis by resection and reanastomosis of the trachea with the aid of cardiopulmonary bypass and early weaning of ventilatory support is recommended. Tracheoplasty using either the castellation technique or slide tracheoplasty is recommended in the treatment of infants with severe (long segment) tracheal stenosis.

Objectives: To characterize otologic management of two patient groups, those with the CHARGE association and those not strictly labeled as CHARGE but with several features of the disorder (CHARGE-like), in order to determine: (1) the clinical validity and utility of managing CHARGE-like children in a similar manner to patients with the strictly defined CHARGE association, (2) the progression and prognosis of hearing loss and (3) the identification of factors that may predict the degree of hearing loss. Design: Case series. Setting: Tertiary care urban children's hospital. Patients: 37 children, 22 in the CHARGE group and 15 in the CHARGE-like group. Interventions: Otorhinolaryngologic and audiologic management. Main outcome measures : Otorhinolaryngologic and audiologic evaluation. Results: All patients required otologic and/or audiologic care. Bilateral hearing loss was found in 32 patients (86%) and unilateral hearing loss in five patients (14%) when hearing was assessed in the absence of otitis media. Among the 32 patients with bilateral hearing loss, 31 (97%) were able to be fit with useful hearing aids. External ear anomalies were present in 25/37 (68%) patients, and middle ear and ossicular anomalies were identified in four cases (4/37, 11%). 36/37(97%) patients required surgical management of otitis media. Three patients (3/37, 8%) exhibited radiographic evidence of inner ear deformity. Facial nerve dysfunction was noted in the records of 14/37 (38%) patients. No statistically significant difference was found when CHARGE and CHARGE-like patients were compared for degree of hearing loss ( P =0.5964), type of hearing loss ( P =0.2657), worsening of hearing level ( P =0.7908), or anomalies of the external ear ( P =0.6921), ossicles ( P =0.7908), inner ear ( P =0.7908) or facial nerve ( P =0.6409). Patients with external ear anomalies did not exhibit statistically different degrees ( P =0.3125) or types ( P =0.1515) of hearing loss from patients without auricular anomalies. The presence of facial nerve anomaly correlated significantly ( P =0.0021) with profound hearing loss. Conclusions: Children who are CHARGE-like may be may be considered equivalent in terms of otologic and audiologic management to children strictly defined as CHARGE patients. These children all require otologic care due to the high prevalence of middle ear disease and the underlying permanent hearing loss that is both stable and aidable. The degree of hearing loss cannot be predicted by external ear morphology, but may be predicted by facial nerve palsy.