Citations

ABSTRACT Introduction Laryngotracheoesophageal clefts (LTEC) are aspiration‐related lesions often assessed using swallow studies and symptoms like respiratory or feeding difficulties. However, these indicators are unreliable predictors of disease severity. Lung inflammation and injury, though significant concerns, are rarely and inconsistently evaluated or reported. As a result, the correlation between swallow study findings and actual pulmonary disease remains unclear. Methods A retrospective cohort of children with LTEC seen in our Aerodigestive Program between October 1, 2012, and September 30, 2023, who underwent videofluoroscopic swallow study (VFSS) or flexible endoscopic evaluation of swallowing (FEES) were included. Data collected included clinical history, risk factors, BAL, chest CT, impedance probe, VFSS/FEES findings, and FOIS‐P/I scores at baseline and follow‐up. Results Eight‐two subjects identified. Lung inflammation and bronchiectasis were common and correlated. Clinical factors, impedance probe, and the presence/severity of swallowing abnormalities on VFSS/FEES were not predictive of lung disease. Fifty‐seven patients underwent LTEC repair for a range of indications, only 49% based on CT and/or BAL findings. Of 57 children who had LTEC repair, only 49% were based on CT or BAL findings. LTEC repair was associated with modest improvement feeding and swallowing. Discussion Children with LTEC have a high prevalence of inflammatory lung disease and injury and undergo repair for a variety of reasons. Swallow studies detect functional swallowing issues but do not reliably identify lung disease. Despite this limitation, LTEC repair is linked to improved feeding and swallowing in some patients, though not all benefit.

Introduction: Laryngotracheoesophageal clefts (LTEC) are well-known aspiration-associated lesions. Results of swallow studies, and respiratory, feeding, and swallowing symptoms are commonly used indications for repair, despite being unclear predictors of disease. Although lung inflammation and injury are primary concerns, such findings are uncommonly and inconsistently evaluated and reported and therefore it remains unclear how well swallow studies predict lung disease. Methods: Children seen in our Aerodigestive program 10/1/2012 and 9/30/2023, with a LTEC and a videofluoroscopic swallow study (VFSS) or flexible endoscopic evaluation of swallowing (FEES) were included. Data regarding clinical history and risk factors, BAL, chest CT, and impedance probe results were abstracted, along with VFSS/FEES results and functional oral intake scale (FOIS-P/I) at baseline and follow-up. Results: 82 subjects identified. Lung inflammation and bronchiectasis were common and correlated. Clinical factors, impedance probe, and the presence/severity of swallowing abnormalities on VFSS/FEES were not predictive of lung disease. 57 patients underwent LTEC repair for a range of indications, only 49% based on CT and/or BAL findings. LTEC repair was associated with a trend towards improvement feeding and swallowing, yet none of these met statistical significance. Discussion: Children with LTEC have a high prevalence of inflammatory lung disease and injury and undergo repair for a variety of reasons. The insufficient ability of swallow study to identify patients with lung disease suggests that such studies identify functional abnormalities but not a disease state, per se. Nevertheless, LTEC repair is associated with improvements in feeding and swallowing in a subset of patients.

AbstractBackgroundAspiration pneumonia is the commonest cause of hospitalizations and death in patients with Parkinson's disease (PD). Among these patients, the relationships between severity of dysphagia, hospitalizations for related complications, and death are not robustly defined. Our aim was to characterize the relationship between PD‐related oropharyngeal dysfunction and clinically relevant outcomes.MethodsRetrospective cohort study of 312 patients with PD at a tertiary center who underwent videofluoroscopic swallow studies conducted by expert therapists between 2010 and 2015. Level of swallowing function was represented using the 7‐point Functional Oral Intake Scale (FOIS) (7 = normal function). Significance and relative risk calculations utilized Poisson regression. Time to composite outcome of first hospitalization or death was summarized using Kaplan‐Meier curve with log‐rank test.Key ResultsOne hundred thirty eight patients had a recorded FOIS score. The prevalence of oropharyngeal dysfunction was 76.1%. The median duration of follow‐up was 26.8 months. In multivariate analyses, patients with FOIS 5 (RR = 2.01 [95% CI: 1.22, 3.32]), FOIS 3 (RR = 2.78 [95% CI: 1.75, 4.40]), and FOIS 1 (RR = 2.50 [95% CI: 1.49, 4.20]) were significantly associated with increased risk of hospitalization or death compared to FOIS 7 after co‐variate adjustments. GERD was also associated with a significant increased risk of hospitalization or death (RR = 1.28 [95% CI: 1.01, 1.64]). Time to first hospitalization or death was shorter in patients with lower FOIS scores (p < 0.00005).Conclusions and InferencesSeverity of oropharyngeal dysphagia, as measured by the FOIS, is associated with poorer survival and shorter time to hospitalization for dysphagia‐related complications, pneumonia, or death in PD.

AbstractBackgroundLimited data exist regarding myopathies with early or prominent dysphagia.MethodsA retrospective study was performed (January 2003 to August 2019) to identify myopathy patients in whom dysphagia was the initial symptom or was disproportionately severe compared with limb weakness.ResultsThirty‐two patients were identified. The median age at diagnosis was 65 y (range, 36–80 y). Inclusion body myositis (IBM) (n = 15), immune‐mediated necrotizing myopathy (IMNM) (n = 5), and oculopharyngeal muscular dystrophy (n = 4), were the most common diagnoses. In 4 patients (3 IMNM and 1 nonspecific myositis) dysphagia evolved rapidly. At evaluation, 21 patients required diet alterations, 5 required feeding tubes, and 8 had aspiration pneumonia. Follow‐up data were available for 20 patients (median, 24 mo). Eight patients received immunosuppressive therapies with improvement in 7, including 3 of 4 with rapidly progressive dysphagia.ConclusionsIBM and IMNM accounted for approximately two‐thirds of patients with early or prominent dysphagia at our institution. Rapidly progressive dysphagia may predict immunotherapy responsiveness.

Secretory carcinoma is a special-type breast carcinoma underpinned by a recurrent t(12;15)(p13;q25) translocation resulting in ETV6-NTRK3 gene fusion. Immunohistochemistry (IHC) using a pan-TRK antibody has been recently shown to help identify NTRK rearrangements in other tumor types. The purpose of this study was to assess the diagnostic utility of pan-TRK IHC in secretory carcinoma of the breast. Pan-TRK IHC was performed using a rabbit monoclonal antibody on whole sections of 24 breast secretory carcinomas and tissue microarray sections of other breast carcinoma types (n=203) and histologic mimics (n=15). Cases were assessed for staining intensity and localization. The 24 patients with secretory carcinoma had a median age of 44 years and a median tumor size of 1.0 cm. ETV6 fluorescence in situ hybridization was positive in all cases tested (n=20). Twenty-three cases (95.8%) showed staining with pan-TRK, which was exclusively nuclear in 19, primarily nuclear with weak cytoplasmic staining in 3, and primarily cytoplasmic with focal nuclear staining in 1. The nuclear staining was diffuse in 17 and at least focally strong in 17. The only pan-TRK negative case was a core biopsy with limited tumor. Among the 203 nonsecretory carcinomas, 21 (10.3%) showed focal, weak nuclear staining in <5% of tumor cells and 1 (0.5%) showed focal membranous staining. All histologic mimics were negative. In conclusion, diffuse and/or at least focally strong nuclear pan-TRK staining is a sensitive and specific marker for secretory carcinoma of the breast.

Abstract Purpose: Although high glucocorticoid receptor (GR) expression in early-stage estrogen receptor (ER)-negative breast cancer is associated with shortened relapse-free survival (RFS), how associated GR transcriptional activity contributes to aggressive breast cancer behavior is not well understood. Using potent GR antagonists and primary tumor gene expression data, we sought to identify a tumor-relevant gene signature based on GR activity that would be more predictive than GR expression alone. Experimental Design: Global gene expression and GR ChIP-sequencing were performed to identify GR-regulated genes inhibited by two chemically distinct GR antagonists, mifepristone and CORT108297. Differentially expressed genes from MDA-MB-231 cells were cross-evaluated with significantly expressed genes in GR-high versus GR-low ER-negative primary breast cancers. The resulting subset of GR-targeted genes was analyzed in two independent ER-negative breast cancer cohorts to derive and then validate the GR activity signature (GRsig). Results: Gene expression pathway analysis of glucocorticoid-regulated genes (inhibited by GR antagonism) revealed cell survival and invasion functions. GR ChIP-seq analysis demonstrated that GR antagonists decreased GR chromatin association for a subset of genes. A GRsig that comprised n = 74 GR activation-associated genes (also reversed by GR antagonists) was derived from an adjuvant chemotherapy-treated Discovery cohort and found to predict probability of relapse in a separate Validation cohort (HR = 1.9; P = 0.012). Conclusions: The GRsig discovered herein identifies high-risk ER-negative/GR-positive breast cancers most likely to relapse despite administration of adjuvant chemotherapy. Because GR antagonism can reverse expression of these genes, we propose that addition of a GR antagonist to chemotherapy may improve outcome for these high-risk patients. Clin Cancer Res; 24(14); 3433–46. ©2018 AACR.