When Can Children Perform Valsalva and Toynbee Maneuvers? An Exploratory Study.

OBJECTIVES: Barochallenge-induced Eustachian tube dysfunction (ETD) is difficult to diagnose because the examination is often normal during clinical assessment. In adults, functional tympanometry testing, performed by asking the patient to Valsalva and Toynbee while measuring the pressure shift, can aid in the diagnosis of ETD. However, standardized values do not exist in children. We aim to determine the age at which children can perform these maneuvers and the normative values in this population. METHODS: Patients with a normal basic ear examination 4 years and older, presenting to the pediatric Otolaryngology clinic, were recruited. Otoscopy, baseline tympanometry, followed by Valsalva and Toynbee maneuvers were performed. Because there are no pediatric norms, we hypothesized that children would achieve the same minimum normal pressure shift as cited in the adult literature (+20 daPa or higher for Valsalva and -20 daPa or lower for Toynbee). The data were analyzed using receiver operating characteristic curves and logistic regression. RESULTS: One hundred sixty-eight children (276 ears) were assessed. Participants as young as 4 years old were able to perform a Valsalva and Toynbee. Age cut-offs at which children achieved adult norms were 12.5 years ( p = 0.016) and 8.5 years ( p = 0.071) for Valsalva and Toynbee maneuvers, respectively. Mean pressure shift ranged from +29 to -36 daPa, and males were 2.5 times more likely to achieve Toynbee compared with females ( p = 0.006). CONCLUSIONS: Functional tympanometry testing may be used to help diagnose barochallenge-induced ETD in older children.

Phase II trial of concurrent sunitinib, temozolomide, and radiotherapy with adjuvant temozolomide for newly diagnosed MGMT unmethylated glioblastoma.

Background: The overall prognosis of glioblastoma (GBM) remains dismal, particularly for patients with unmethylated O6-methylguanine-DNA-methyltransferase (MGMT) promoter. In this phase II trial, we tested the combination of the antiangiogenic agent sunitinib with radiotherapy and temozolomide (TMZ) for newly diagnosed unmethylated MGMT GBM patients. Methods: We enrolled 37 patients with unmethylated MGMT promoter GBM, age 18-70, and KPS ≥70. Patients received 12.5 mg of daily sunitinib for 7 days, followed by concurrent chemoradiation plus 12.5 mg sunitinib, then adjuvant TMZ. The primary endpoint was progression-free survival (PFS), and secondary endpoints were overall survival (OS), safety, and neutrophil-to-lymphocyte ratio (NLR) biomarker. Results: At a median follow-up time of 15.3 months (range: 3.1-71.3 months), the median PFS was 7.15 months (95% CI: 5.4-10.5) and the 6-month PFS was 54.0%. Median OS was 15.0 months (95% CI: 13.8-19.4) and 2-year OS rate was 17.1%. Patients receiving >3 cycles of adjuvant TMZ, undergoing surgery at progression, and presenting a post-concurrent NLR ≤6 experienced a significant improved OS with hazard ratios of 0.197 (P = .001), 0.46 (P = .049), and 0.38 (P = .021), respectively, on multivariable analysis. Age >65 years predicted for worse OS with hazard ratio of 3.92 (P = .037). Grade ≥3 thrombocytopenia occurred in 22.9%, grade ≥3 neutropenia in 20%, and grade ≥3 thromboembolic events in 14.3% of patients. There were no grade 5 events. Conclusion: Our findings suggest a potential benefit of combining sunitinib with chemoradiation in newly diagnosed GBM patients with unmethylated MGMT status and provide a strong rationale to test this combination in future studies.

Predictors of dysplastic and neoplastic progression of Barrett's esophagus

Background: It is unknown why some cases of Barrett's esophagus progress to invasive malignant disease rapidly while others do so more slowly or not at all. The aim of this study was to identify demographic and endoscopic factors that predict dysplastic and neoplastic progression in patients with Barrett's esophagus. Methods: Patients with Barrett's esophagus who were assessed in 2000­2010 were assessed for inclusion in this retrospective study. Demographic and endoscopic variables were collected from an endoscopy database and the medical chart. Dysplastic and neoplastic progression was examined by time-to-event analysis. We used Cox proportional hazard regression modelling and generalized estimating equation methods to identify variables that were most predictive of neoplastic progression. Results: A total of 518 patients had Barrett's esophagus confirmed by endoscopy and pathology and at least 2 surveillance visits. Longer Barrett's esophagus segment (≥ 3 cm) (odds ratio [OR] 1.2, 95% confidence interval [CI] 1.1­1.3) and increased age (≥ 60 yr) (OR 3.5, 95% CI 1.7­7.4) were independent predictors of progression from nondysplasia to dysplastic or neoplastic grades. Presence of mucosal irregularities (OR 8.6, 95% CI 2.4­30.4) and increased age (OR 5.1, 95% CI 1.6­16.6) were independent predictors of progression from nondysplasia to high-grade dysplasia or adenocarcinoma. Conclusion: Increased age, longer Barrett's segment and presence of mucosal irregularities were associated with increased risk of dysplastic and neoplastic progression. In addition to dysplasia, these factors may help stratify patients according to risk of neoplastic progression and be used to individualize surveillance. More prospective studies with larger samples are required to validate these results.

Contexte: On ignore pour quelle raison certains cas d'oesophage de Barrett évoluent rapidement vers une maladie maligne envahissante, tandis que d'autres progressent lentement ou se stabilisent. Le but de cette étude était d'identifier les facteurs démographiques et endoscopiques prédicteurs d'une progression dysplasique et néoplasique chez les patients porteurs d'un oesophage de Barrett. Méthodes: Des patients présentant un oesophage de Barrett ayant été examinés entre 2000 et 2010, ont été évalués en vue de leur participation à cette étude rétrospective. Les variables démographiques et endoscopiques ont été recueillies à partir d'une base de données endoscopiques et des dossiers médicaux. La progression dysplasique et néoplasique a été évaluée par analyse du délai de survenue de l'événement. Nous avons utilisé le modèle de la régression de Cox (risques proportionnels) et les équations d'estimation généralisée afin d'identifier les variables les plus prédictives d'une progression néoplasique. Résultats: En tout, 518 patients présentaient un oesophage de Barrett confirmé par examen endoscopique et anatomopathologique et comptaient au moins 2 visites de surveillance. La présence de segments d'oesophage de Barrett plus longs (≥ 3 cm) (rapport des cotes [RC] 1,2, intervalle de confiance à 95 % [IC] 1,1­1,3) et un âge avancé (≥ 60 ans) (RC 3,5, IC à 95 % 1,7­7,4) ont été des prédicteurs indépendants de progression d'un grade non dysplasique vers un grade dysplasique. La présence d'irrégularités muqueuses (RC 8,6, IC à 95 % 2,4­30,4) et l'âge avancé (RC 5,1, IC à 95 % 1,6­16,6) ont été des prédicteurs indépendants de progression de la non-dysplasie vers une dysplasie de haut grade ou l'adénocarcinome. Conclusion: L'âge avancé, des segments d'oesophage de Barrett plus longs et la présence d'irrégularités muqueuses ont été associés à un risque accru de progression dysplasique et néoplasique. En plus de la dysplasie, ces facteurs peuvent faciliter la stratification des patients selon le risque de progression néoplasique et servir à individualiser la surveillance. Il faudra procéder à d'autres études prospectives auprès d'échantillons de population plus volumineux pour valider ces résultats.