Andre Isaac

Detection of human papillomavirus type 16 in oropharyngeal squamous cell carcinoma using droplet digital polymerase chain reaction.

The incidence of oropharyngeal squamous cell carcinoma caused by oncogenic HPV (HPV‐OPSCC) is rising worldwide. HPV‐OPSCC is commonly diagnosed by RT‐qPCR of HPV‐16 E6 and E7 oncoproteins or by cyclin‐dependent kinase inhibitor 2A, multiple tumor suppressor 1 (p16) immunohistochemistry (IHC). Droplet digital PCR (ddPCR) has been recently reported as ultra‐sensitive and highly precise method of nucleic acid quantification for biomarker analysis. We aimed to validate this method for the detection of HPV‐16 E6 and E7 in HPV‐OPSCC.

Quality of Reporting and Evidence in American Academy of Pediatrics Guidelines

OBJECTIVES: The primary objectives were to evaluate the quality of development and reporting of American Academy of Pediatrics (AAP) guidelines and to determine the level of evidence underlying the recommendations. METHODS: Two reviewers scored each guideline by using the Appraisal of Guidelines for Research and Evaluation II (AGREE-II) instrument and determined the level of evidence for each recommendation in each guideline. Subgroup analyses compared AAP guidelines published before and after key changes in AAP guideline development policy and compared internal with endorsed guidelines. RESULTS: For the 28 current guidelines, the highest average scores on AGREE-II were in scope and purpose (75%) and clarity of presentation (73%). The lowest average scores were in editorial independence (17%) and applicability (30%). The only domain that improved after AAP policy updates was editorial independence (P = .01). Of the 190 treatment recommendations, 43% were based on experimental studies, 30% on observational studies, and 27% on expert opinion or no reference. Compared with early guidelines, late guidelines included a higher proportion of treatment recommendations based on experimental studies (P = .05). CONCLUSIONS: There was no clear improvement in the quality of development and reporting of AAP clinical practice guidelines over time. Routine application of AGREE-II to guideline development could enhance guideline quality. The proportion of guideline recommendations based on experimental evidence has increased slightly over time. Pediatric research agendas should be matched to vital gaps in the evidence underlying pediatric guidelines.

Correlations Between Acoustic Rhinometry, Subjective Symptoms, and Endoscopic Findings in Symptomatic Children With Nasal Obstruction

IMPORTANCE Nasal obstruction is common in children and difficult to quantify objectively. Symptom quantification is paramount for surgical and medical decision making. Acoustic rhinometry is a relatively new technique aimed at the objective assessment of nasal obstruction. There is no standardized method for the objective assessment of the pediatric nasal airway. OBJECTIVE To explore the correlations between acoustic rhinometry (AR), subjective symptoms, and endoscopic findings in children presenting with nasal obstruction. DESIGN, SETTING, AND PARTICIPANTS A cross-sectional, exploratory, diagnostic study of prospectively collected data from a multidisciplinary airway clinic (pulmonology, orthodontics, and otolaryngology) database at a tertiary academic referral center. Data were collected over a 2-year period (2010-2012) from 65 nonsyndromic children (38 boys) 7 years and older (mean [SD] age, 10.3 [2.5] years [range, 7-14 years]), presenting with persistent nasal obstructive symptoms for at least 1 year, without signs and symptoms of sinus disease. INTERVENTIONS We collected patient demographics and medical history information including allergy, asthma, and sleep-disordered breathing. Subjective nasal obstruction was scored using a visual analog scale (VAS). Sleep-disordered breathing was assessed using overnight pulse oximetry. The adenoid size, septal position, and visual severity of chronic rhinitis (endoscopic rhinitis score [ERS]) were rated on nasal endoscopy by 2 independent reviewers and validated by agreement. Acoustic rhinometry (AR) was undertaken before and after use of a decongestant. MAIN OUTCOMES AND MEASURES Correlation and multiple regression analyses were performed to explore interrelationships between subjective nasal obstruction VAS, AR, and nasal endoscopy. RESULTS Among the 65 patients, 28 (43%) had symptoms of sleep-disordered breathing, 14 (22%) had allergic rhinitis, 10 (15%) had asthma, 27 (41%) had grade 3 or 4 adenoidal obstruction, 28 (43%) had an ERS of 2, 6 (9%) had an ERS of 3, and 19 (29%) had septal deviation. Significant correlations were found between subjective nasal obstruction VAS score and ERS (r = -0.364, P = .003), ERS and minimal cross-sectional area before decongestion (r = -0.278, P = .03), and adenoid size and calculated nasal resistance after decongestion (r = 0.430, P < .001). Multiple regression analysis showed that the ERS was the only significant predictor of VAS score (β of -22.089; 95% CI, -35.56 to -8.61 [P = .002]). No predictors were identified for AR variables. CONCLUSIONS AND RELEVANCE Among the evaluated tools, endoscopy appears to be the most reliable tool to estimate the degree of subjective nasal symptoms.

Predictors of non-diagnostic cytology in surgeon-performed ultrasound guided fine needle aspiration of thyroid nodules

BackgroundFine needle aspiration (FNA) is the standard of care for the diagnostic work-up of thyroid nodules but despite its proven utility, the non-diagnostic rate for thyroid FNA ranges from 6-36%. A non-diagnostic FNA is problematic for the clinician and patient because it can result in repeated procedures, multiple physician visits, and a delay in definitive treatment. Surgeon-performed FNA has been shown to be safe, cost-effective, as accurate as those performed by other clinicians, and has the added benefit of decreasing wait times to surgery. Several studies have examined rates and factors that may be predictive of a non-diagnostic cytology in non-surgeon FNA, but none have evaluated this in surgeon-performed thyroid FNA. If these factors are unique in surgeon-performed vs. non-surgeon performed thyroid FNA, then patients may be more appropriately triaged to FNA by alternate clinicians.ObjectivesThe purpose of this study was to determine the rate and factors predictive of a non-diagnostic FNA in surgeon performed ultrasound-guided FNA of thyroid nodules.MethodsWe conducted a retrospective review of all adult patients who underwent thyroid FNA by a staff, fellow, or resident Otolaryngologist at the University of Alberta between January 2011 and June 2013. Factors analyzed included patient factors, thyroid characteristics, nodule characteristics, and surgeon level of training and experience. Univariate and multivariate binary logistic regression analysis were performed.Results131 patients (180 nodules) were reviewed. The non-diagnostic rate was 23%. Nodules with predominant cystic component, those less than 1 cm, and resident-performed FNA were associated with non-diagnostic cytology (p = 0.001, p = 0.02, p = 0.04 respectively). A cystic nodule was the only independent predictor of non-diagnostic FNA on multivariate analysis (OR = 4.441, 95% CI [1.785-11.045], p = 0.001).ConclusionsThe rate of non-diagnostic thyroid FNA performed by a surgeon with ultrasound guidance is similar to other clinicians. A cystic nodule is a strong independent predictor of non-diagnostic cytology. Non-cystic nodules may particularly benefit from surgeon-performed thyroid FNA due to the high diagnostic rate and potential for earlier definitive management.

Ultrasensitive detection of oncogenic human papillomavirus in oropharyngeal tissue swabs

BackgroundThe incidence of oropharyngeal squamous cell carcinoma (OPSCC) caused by oncogenic human papillomavirus (HPV) is rising worldwide. HPV-OPSCC is commonly diagnosed by RT-qPCR of HPV E6 and E7 oncoproteins or by p16 immunohistochemistry (IHC). Droplet digital PCR (ddPCR) has been recently reported as an ultra-sensitive and highly precise method of nucleic acid quantification for biomarker analysis. To validate the use of a minimally invasive assay for detection of oncogenic HPV based on oropharyngeal swabs using ddPCR. Secondary objectives were to compare the accuracy of ddPCR swabs to fresh tissue p16 IHC and RT-qPCR, and to compare the cost of ddPCR with p16 IHC.MethodsWe prospectively included patients with p16+ oral cavity/oropharyngeal cancer (OC/OPSCC), and two control groups: p16− OC/OPSCC patients, and healthy controls undergoing tonsillectomy. All underwent an oropharyngeal swab with ddPCR for quantitative detection of E6 and E7 mRNA. Surgical specimens had p16 IHC performed. Agreement between ddPCR and p16 IHC was determined for patients with p16 positive and negative OC/OPSCC as well as for healthy control patients. The sensitivity and specificity of ddPCR of oropharyngeal swabs were calculated against p16 IHC for OPSCC.Results122 patients were included: 36 patients with p16+OPSCC, 16 patients with p16−OPSCC, 4 patients with p16+OCSCC, 41 patients with p16−OCSCC, and 25 healthy controls. The sensitivity and specificity of ddPCR of oropharyngeal swabs against p16 IHC were 92 and 98% respectively, using 20–50 times less RNA than that required for conventional RT-qPCR. Overall agreement between ddPCR of tissue swabs and p16 of tumor tissue was high at ĸ = 0.826 [0.662-0.989].ConclusionOropharyngeal swabs analyzed by ddPCR is a quantitative, rapid, and effective method for minimally invasive oncogenic HPV detection. This assay represents the most sensitive and accurate mode of HPV detection in OPSCC without a tissue biopsy in the available literature.

A systematic review of the evidence on spontaneous resolution of laryngomalacia and its symptoms

INTRODUCTION AND OBJECTIVES Laryngomalacia (LM) is the most common cause of congenital stridor. Tradition holds that the majority of patients resolve spontaneously by 12-18 months of age. The objective of this study was to systematically review the literature on the spontaneous resolution of LM and/or its presenting symptoms, in otherwise healthy infants. METHODS Data sources included Medline/PubMed, EMBASE, Scopus, CINAHL, Proquest, Cochrane database, Cochrane Methodology Register, Web of Science Conference Proceedings Citation Index, and ACP Journal Club. Study inclusion criteria included participants with an endoscopic diagnosis of LM, and symptoms of stridor, swallowing dysfunction, and/or snoring/sleep-disordered breathing, that documented subjective or objective resolution endpoints. Surgical series, case reports, and narrative reviews were excluded. Studies with insufficient follow-up (<3 months), and patients with comorbidities without subgroup analysis were excluded. Two independent reviewers extracted follow-up duration, rate of retention, time to resolution of LM, and method of documentation of resolution. RESULTS Of the 1146 articles identified, three met inclusion/exclusion criteria (n=411 patients). All were retrospective and used stridor resolution as the only endpoint. Resolution rate was 89%, with time to resolution ranging from 4 to 42 months. Level of evidence was low, and studies suffered from lack of follow-up, and no objective endpoints. Meta-analysis was not possible. CONCLUSIONS Endoscopic evidence of the natural history of laryngomalacia and its resolution is lacking. Low level of evidence supports that stridor and respiratory distress resolve, but the range of the time to resolution and rate of resolution is wide. Other clinical manifestations have not been studied. Prospective longitudinal trials are required to better understand the natural history.

Does drug-induced sleep endoscopy change the surgical decision in surgically naïve non-syndromic children with snoring/sleep disordered breathing from the standard adenotonsillectomy? A retrospective cohort study

BackgroundAdenotonsillectomy is the most commonly performed operation for pediatric snoring/sleep disordered breathing (S/SDB). However, 20–40% of patients will fail to improve. Drug-induced sleep endoscopy (DISE) may provide a more individualized surgical plan and limit unsuccessful surgeries. The aim of this study was to assess the impact of DISE on surgical decision-making in surgically naïve children with S/SDB.MethodsA retrospective observational cohort study was undertaken at the Stollery Children’s Hospital. Patients 3–17 years of age who underwent DISE-directed surgery for S/SDB between January 2009 and December 2015 were eligible. We excluded other indications for tonsillectomy and syndromic children. The primary outcome was the level of agreement between a DISE-based surgical decision and the reference standard based on the American Academy of Pediatrics (AAP) guidelines via un-weighted Cohen’s kappa. Secondary outcomes included the frequency and type of alternate surgical targets identified by DISE. The agreement on tonsil size between in-office physical assessment and DISE was also calculated. The effectiveness of DISE-directed surgery on postoperative S/SDB was not investigated.ResultsFive hundred fifty-eight patients were included. DISE changed the surgical plan in 35% of patients. Agreement between DISE-based and AAP clinical practice guidelines-based management was low (κ = 0.354 +/- 0.021 [95% CI 0.312–0.395]). An alternate diagnosis or surgical target was identified by DISE in 54% of patients. There was moderate agreement on tonsil size (κ = 0.44 [0.33–0.55]) between DISE and in-office clinical assessment.ConclusionsThis is a first phase diagnostic study, which demonstrates that DISE affects decision-making in surgically naïve children with S/SDB in up to 35% of patients. It has utility in individualizing first stage surgical treatments as well as identifying alternate targets for further surgical or medical therapy, while potentially limiting unsuccessful surgeries. Further studies to examine the effect of DISE on surgical outcomes are required.

Predictors of Failed and Delayed Decannulation after Head and Neck Surgery

Objective To determine the variables that are predictive of failed decannulation (FD), delayed decannulation (DD), and days to decannulation in patients who underwent head and neck cancer resection with free tissue transfer reconstruction for head and neck squamous cell carcinoma. Design Case series with chart review. Setting Tertiary care otolaryngology–head and neck surgery referral center. Subject and Methods Patients (N = 108) were included who underwent head and neck cancer resection with free tissue transfer reconstruction and tracheostomy between 2011 and June 2014. Patients with laryngectomy, previous tracheostomy, and other airway pathology necessitating tracheotomy were excluded. Preoperative patient variables and cancer site/staging variables were analyzed, as well as extent of structures resected and type of reconstruction. Univariate and multivariate binary logistic and Cox regression analyses were used to determine predictors of FD and DD. Cox regression analysis was used to determine predictors of days to decannulation. Results Of the 108 included patients, 16 had FD, and 26 had DD. Univariate analysis demonstrated that advanced stage (r = 0.233, P = .021), total glossectomy (r = 0.924, P < .001), anterolateral thigh flap reconstruction (r = 0.906, P < .001), smoking at time of surgery (r = 0.319, P = .002), and pack years (r = 0.322, P = .001) were associated with FD. Cox regression analysis showed that total glossectomy, exp(B) = 15.837 (95% confidence interval [95% CI]: 1.949-128.679); anterolateral thigh flap reconstruction, exp(B) = 8.439 (95% CI: 2.435-29.620); and smoking status, exp(B) = 2.970 (95% CI: 1.617-5.456) were independent predictors of days to decannulation and FD. Conclusions Patients with total glossectomy defects and those who continue to smoke are at increased risk for FD and DD. Aggressive smoking cessation programs may decrease the risk of FD and DD. Patients should be counseled about their risk profiles.

Laryngomalacia, Supraglottoplasty, and Feeding and Swallowing Disorders: Is There An Association?

Laryngomalacia (LM) is a commonly encountered entity in infants and children with stridor and other upper aerodigestive symptoms [1]. Although the presentation and functional deficits encompass stridor, cyanotic spells, failure to thrive, and feeding and swallowing disorders (FSD), traditionally, the main focus had been on the respiratory impairment. The earlier and majority of the literature has been concerned mainly with the most severe cases whose life or thriving was at risk and the assessment of surgical success to relieve them [2]. Later research examined the association of LM with sleep-disordered breathing (SDB) [3], and only relatively recently has interest been directed toward the impact of FSD.

Correlation between gonial angle and dynamic tongue collapse in children with snoring/sleep disordered breathing – an exploratory pilot study

BackgroundDrug induced sleep endoscopy (DISE) is hoped to identify reasons of failure of adenotonsillectomy (AT) in treating pediatric sleep disordered breathing (SDB). Maxillomandibular disproportion has been studied as another association which may explain alternative pathogenesis of SDB. We aimed to explore the relation between the size of the gonial angle and inclination of the epiglottis measured from cone beam CT (CBCT) and tongue base collapse based on DISE in children with SDB.MethodA retrospective chart review was conducted at a tertiary pediatric center. Children (6-17 years old) assessed at a multi-disciplinary Upper Airway Clinic, diagnosed with SDB and maxillo-mandibular disproportion (MMD), and who underwent DISE were eligible. Variables obtained from the electronic medical records of the clinic and prospective database included demographics, comorbidities, surgeries performed, investigations, DISE findings and CBCT findings. The gonial angle of subjects with and without tongue base collapse (TBC) on SNP were compared.ResultsIn total 29 patients (13 male, 8 female) age 6-17 (median= 9) were eligible for the study from January 2009 – July 2016. We included 11 subjects, and 10 comparators. The mean gonial angle of the TBC group was 139.3°± 7.6°, while that of the comparison group was 129.4°±3.5 (mean difference -9.937, 95% CI of -15.454 to - 4.421, P = 0.001, power of test 0.95). Additionally, the mean inclination of the epiglottis had a mild positive correlation (r=0.32, p<0.05) with the gonial angle, in the whole cohort.ConclusionsThis pilot study suggests that TBC may be mediated by a wider gonial angle in children with SDB patients. The posterior tilt of the epiglottis on CBCT may be a surrogate sign of TBC.