To review the current literature about the epidemiology, clinical presentation, diagnosis, and treatment of laryngopharyngeal reflux (LPR).
PubMed, Cochrane Library, and Scopus.
A comprehensive ...review of the literature on LPR epidemiology, clinical presentation, diagnosis, and treatment was conducted. Using the PRISMA statement, 3 authors selected relevant publications to provide a critical analysis of the literature.
The important heterogeneity across studies in LPR diagnosis continues to make it difficult to summarize a single body of thought. Controversies persist concerning epidemiology, clinical presentation, diagnosis, and treatment. No recent epidemiologic study exists regarding prevalence and incidence with the use of objective diagnostic tools. There is no survey that evaluates the prevalence of symptoms and signs on a large number of patients with confirmed LPR. Regarding diagnosis, an increasing number of authors used multichannel intraluminal impedance-pH monitoring, although there is no consensus regarding standardization of the diagnostic criteria. The efficiency of proton pump inhibitor (PPI) therapy remains poorly demonstrated and misevaluated by incomplete clinical tools that do not take into consideration many symptoms and extralaryngeal findings. Despite the recent advances in knowledge about nonacid LPR, treatment protocols based on PPIs do not seem to have evolved.
The development of multichannel intraluminal impedance-pH monitoring and pepsin and bile salt detection should be considered for the establishment of a multiparameter diagnostic approach. LPR treatment should evolve to a more personalized regimen, including diet, PPIs, alginate, and magaldrate according to individual patient characteristics. Multicenter international studies with a standardized protocol could improve scientific knowledge about LPR.
Several studies have highlighted the diagnostic potential of salivary microRNA (miRNA) in head and neck squamous cell cancer (HNSCC). The purpose of this meta-analysis was to summarize published ...studies and evaluate the diagnostic accuracy of salivary miRNA in HNSCC detection. In this meta-analysis, we systematically searched PubMed, EMBASE, and Cochrane Library databases for studies on miRNA and HNSCC diagnosis. Pooled sensitivity, specificity, and diagnostic odds ratio (DOR) with a summary receiver-operating characteristic curve were calculated using a bivariate random-effect meta-analysis model. Furthermore, subgroup analyses were conducted to explore the main sources of heterogeneity. Seventeen studies from ten articles, including 23 miRNA and a total of 759 subjects, were included in this meta-analysis. The pooled sensitivity and specificity of salivary miRNA in the diagnosis of HNSCC were 0.697 (95% CI: 0.644–0.744) and 0.868 (95% CI: 0.811–0.910), respectively. The overall area under the curve was 0.803 with a DOR of 12.915 (95% CI: 9.512–17.534). Salivary miRNAs are a promising non-invasive diagnostic biomarker with moderate accuracy for HNSCC. These results must be verified by large-scale prospective studies.
Objectives/Hypothesis
To determine salivary pepsin levels as a function of collection time.
Study Design
A prospective, case‐control study.
Methods
We selected 57 patients with clinical symptoms and ...signs of laryngopharyngeal reflux who underwent 24‐hour multichannel intraluminal impedance‐pH (24h MII‐pH) monitoring tests, and 12 control subjects without clinical symptoms and signs of laryngopharyngeal reflux. All subjects were instructed to collect saliva samples upon waking, 1 hour after each meal (3 times per day), and upon any occurrence of laryngopharyngeal reflux (LPR) symptoms. The pepsin levels in saliva were measured by using enzyme‐linked immunosorbent assay. The Reflux Symptom Index survey was also administered.
Results
A total of 50 patients in whom LPR was diagnosed based on results of 24h MII‐pH monitoring test were enrolled in the study. The average pepsin level upon waking was 17.2 ng/mL, which was significantly higher than that measured in samples collected at any other time (P < .005). Pepsin levels were higher in patients with LPR than those in controls. The Reflux Symptom Index scores were statistically different between these groups of subjects.
Conclusions
The levels of total pepsin in saliva collected upon waking were significantly higher in the group of patients presenting with LPR symptoms and who demonstrated at least one episode of proximal esophageal reflux during 24h MII‐pH monitoring. Furthermore, the average pepsin level upon waking was higher than that measured at any other time. Measuring pepsin levels in the saliva upon waking may be a useful method in the diagnosis of LPR.
Level of Evidence
3b Laryngoscope, 126:2770–2773, 2016
Oral microbiota can alter cancer susceptibility and progression by modulating metabolism and inflammation. We assessed the association between the oral microbiome and lymph node (LN) metastasis in ...oral squamous cell carcinoma (OSCC). We collected a total of 54 saliva samples from patients with OSCC before surgery. LN metastasis was assessed based on postoperative pathological examination. We used QIIME2, linear discriminant analysis effect size (LEfSe), and PICRUSt2 methods to analyze microbial dysbiosis. A random forest classifier was used to assess whether the oral microbiome could predict LN metastasis. Among the 54 OSCC samples, 20 had LN metastasis, and 34 had no evidence of metastasis. There was a significant difference in β-diversity between the metastasis and no metastasis groups. Through LEfSe analysis, the metastasis group was enriched in the genera Prevotella, Stomatobaculum, Bifidobacterium, Peptostreptococcaceae, Shuttleworthia and Finegoldia. Pathways related to signal peptidase II were predominant in the no metastasis group. The RF model showed a modestly high accuracy for predicting metastasis. Differences in microbial community composition and functions were observed in the oral microbiome of patients with OSCC with and without LN metastasis. However, the finding that specific taxa may be associated with LN metastasis should be verified in a further prospective study.
In this study we assessed the clinical significance of an epithelial-mesenchymal transition (EMT) gene signature and explored its association with the tumor microenvironment related to immunotherapy ...in patients with head and neck squamous cell carcinoma (HNSCC). Genes were selected when mRNA levels were positively or negatively correlated with at least one well-known EMT marker. We developed an EMT gene signature consisting of 82 genes. The patients were classified into epithelial or mesenchymal subgroups according to EMT signature. The clinical significance of the EMT signature was validated in three independent cohorts and its association with several immunotherapy-related signatures was investigated. The mesenchymal subgroup showed worse prognosis than the epithelial subgroup, and significantly elevated PD-1, PD-L1, and CTLA-4 levels, and increased interferon-gamma, cytolytic, T cell infiltration, overall immune infiltration, and immune signature scores. The relationship between PD-L1 expression and EMT status in HNSCC after treatment with TGF-β was validated in vitro. In conclusion, the EMT gene signature was associated with prognosis in HNSCC. Additionally, our results suggest that EMT is related to immune activity of the tumor microenvironment with elevated immune checkpoint molecules.
This study aimed to evaluate the characteristics of reflux in proton pump inhibitor (PPI) nonresponders vs responders in patients with laryngopharyngeal reflux (LPR) by using 24-hour multichannel ...intraluminal impedance-pH (MII-pH) monitoring.
Prospective cohort study.
A tertiary care otolaryngology clinic.
Patients with typical LPR symptoms showing >1 proximal reflux episode were considered to have LPR and investigated prospectively. Patients were prescribed high-dose PPI twice daily and followed up for at least 2 months. Patients with LPR showing a ≥50% decrease in the follow-up reflux symptom index score during treatment periods as compared with pretreatment were defined as responders; others were defined as nonresponders. Various parameters in 24-hour MII-pH monitoring between nonresponders and responders with LPR were compared with Student's
test and receiver operating characteristic curve.
Eighty patients were diagnosed with LPR and categorized as nonresponders (n = 19) and responders (n = 61). Proximal all reflux time and proximal longest reflux time in various MII parameters were higher in responders than in nonresponders (
= .0040 and .0216, respectively). Proximal all reflux time >0.000517% was a better cutoff value to predict responders with LPR as compared with the proximal longest reflux time >0.61 minutes (sensitivity + specificity: 1.317 vs 1.291).
Proximal all reflux time in various 24-hour MII-pH monitoring parameters can be helpful to predict the response to PPI therapy in patients with LPR. These findings will help establish a personalized therapeutic scheme for patients with LPR.
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► We prepare graphene/epoxy composite films by solution casting and thermal curing. ► We exploit structures and electrical properties of the composite films. ► The composite films ...show excellent electric heating behavior. ► The composites have rapid temperature response and high electric power efficiency. ► High operational stability at applied voltages are also confirmed.
We have prepared a series of graphene/epoxy composite films by thermal curing of diglycidyl ether of bisphenol-A with an amine-functionalized agent casted on a polyimide film, and investigated their structures and electrical properties as a function of graphene content of 0.0–10.0wt%. X-ray diffraction patterns and TEM images show that graphene nanoplatelets are well dispersed in the epoxy resin matrix. The electrical resistance of the composite films varies dramatically from ∼1013 to ∼103Ω with increasing the graphene content, especially at a certain graphene content between 1.0 and 2.0wt%. Accordingly, electric heating behavior of the composite films with 2.0–10.0wt% graphene is strongly dependent on graphene content as well as applied voltage. For the composite film with 10.0wt% graphene, a maximum temperature of ∼126°C is stably maintained over a cyclic voltage variation of 30V. The excellent electric heating performance such as rapid temperature response, high electric power efficiency, and operational stability at applied voltages is believed to be owing to the presence of highly conductive graphene sheets interconnected in the thermosetting epoxy matrix.
Although numerous studies have used systemic approaches to identify prognostic predictors in oral squamous cell carcinoma (OSCC), the effectiveness of these approaches has not been assessed ...clinically. Further, the mechanism underlying malignant behaviors in OSCC is poorly characterized. This study aimed to develop and verify accurate prognostic predictors for OSCC patients and assess the associated biology. We identified an OSCC‐recurrence‐related gene signature (ORGS) using a Cox regression analysis. Functional enrichment analysis was used to identify enriched pathways and biological processes to reveal the underlying mechanism of OSCC malignant behavior. The ORGS successfully divided OSCC patients into low‐ and high‐risk groups with significantly different overall survivals. Pathway analysis revealed oxidative phosphorylation (OXPHOS) as a signaling pathway associated with the ORGS in OSCC. Interestingly, high OXPHOS status was strongly associated with poor overall survival in OSCC patients. Mediator complex subunit 30 (MED30) was a predicted upstream regulator of OXPHOS, and knockdown of MED30 reduced histone acetylation. We identified that the ORGS was strongly correlated with OXPHOS regulatory processes, suggesting OXPHOS as a key mechanism leading to poor prognosis in OSCC.
Here, we define a gene signature from oral squamous cell carcinoma (OSCC) patients which could stratify patients into low and high‐risk groups with different overall survival. We highlight oxidative phosphorylation (OXPHOS) as a signaling pathway associated with this signature. Finally, we demonstrate that MED30‐induced OXPHOS gene transcription depolarizes mitochondrial membrane potential and inhibits ROS‐dependent apoptosis of cancer cells.
The FAT1 gene functions as a tumor suppressor or promoter and remains incompletely understood. We examined the clinical significance of FAT1 in head and neck squamous cell carcinoma (HNSCC) using ...four publicly available HNSCC cohorts and one HNSCC cohort enrolled at a tertiary medical center. We developed FAT1 signatures reflecting FAT1 mutations and mRNA expression using one cohort. Patients with HNSCC were classified into FAT1‐associated low risk (FAT1‐LR; n = 195) and FAT1‐associated high risk (FAT1‐HR; n = 371) subgroups. The five‐year overall survival and recurrence‐free survival rates were significantly lower in the FAT1‐HR subgroup than in the FAT1‐LR subgroup (P = 0.01 and 0.003, respectively). The clinical significance of FAT1 was validated using four independent cohorts. Cox proportional hazards models showed that the FAT1 signature was an independent prognostic factor for HNSCC patients. In addition, FAT1 signature was associated with the response to radiotherapy, advanced stage, and human papilloma virus (HPV) status in HNSCC patients. In conclusion, the FAT1 gene signature was associated with prognosis of HNSCC and may help to provide personalized treatments for HNSCC patients.
In our study, we classified patients with head and neck squamous cell carcinoma (HNSCC) as FAT1‐associated low risk and FAT1‐associated high risk, based on our predefined FAT1 gene‐related molecular signature. The prognosis of patients with HNSCC was significantly different between both subgroups. In conclusion, the FAT1 signature served as an independent prognostic factor for HNSCC and was associated with response to radiation therapy.
Background
This study aimed to develop and compare machine learning (ML) based predictive models for lymph node metastasis (LNM) in early T classification oral squamous cell carcinoma (OSCC).
Methods
...We used data from the Surveillance Epidemiology and End Results Database to develop and validate the predictive models for LNM in patients with T1, T2 OSCC. Using simple clinical and histopathological data, we developed six ML algorithms to predict LNM. The predictive performance of models was compared.
Results
The areas under the receiver operating characteristic curves (AUCs) of the six models ranged from 0.768 to 0.956. The best prediction performance was achieved with a XGBoost (AUC = 0.956). Permutation importance analysis showed that tumor size is the most important feature in predicting metastasis.
Conclusions
We developed a simplified and reproducible ML‐based predictive model for metastasis in early T classification OSCC that could be helpful for the decision of a treatment strategy.
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