Childhood passive smoke exposure is associated with adult head and neck cancer

Introduction: Passive smoke is carcinogenic but its association with head and neck squamous cell carcinoma (HNSCC) is uncertain. Methods: We conducted a case-control study of childhood passive smoke exposure (CPSE) and HNSCC in 858 cases and 806 frequency-matched controls using an interviewer-administered questionnaire. Odds ratios (OR) and 95% confidence intervals (CI) were estimated with logistic regression controlling for adult smoking in the total study population, and in never-smokers only (184 cases and 415 controls). CPSE was also studied in oropharyngeal separately from other HNSCC using polytomous logistic regression. Results: CPSE was associated with HNSCC (OR, 1.28; 95% CI, 1.01–1.63) after controlling for adult smoking and other factors. This association was similar in magnitude, although not statistically significant, among subjects who never smoked as adults (OR, 1.19, 95% CI, 0.80–1.76). CPSE was associated more strongly with oropharyngeal cancer (a HNSCC subtype commonly associated with human papillomavirus (HPV) infection) than with HNSCC at non-oropharyngeal sites (OR, 2.02; 95% CI, 1.01–4.06, N = 52 cases vs. OR, 1.04; 95% CI, 0.68–1.60, N = 132 cases; P-for-heterogeneity = 0.08). Conclusions: Data from this large US-based case control study suggest a role for CPSE in HNSCC etiology.     

Promoter hypermethylation using 24-gene array in early head and neck cancer: Better outcome in oral than in oropharyngeal cancer

Silencing of tumor suppressor genes (TSGs) by DNA promoter hypermethylation is an early event in carcinogenesis and a potential target for personalized cancer treatment. In head and neck cancer, little is known about the role of promoter hypermethylation in survival. Using methylation specific multiplex ligation-dependent probe amplification (MS-MLPA) we investigated the role of promoter hypermethylation of 24 well-described genes (some of which are classic TSGs), which are frequently methylated in different cancer types, in 166 HPV-negative early oral squamous cell carcinomas (OSCC), and 51 HPV-negative early oropharyngeal squamous cell carcinomas (OPSCC) in relation to clinicopathological features and survival. Early OSCC showed frequent promoter hypermethylation in RARB (31% of cases), CHFR (20%), CDH13 (13%), DAPK1 (12%), and APC (10%). More hypermethylation (≥ 2 genes) independently correlated with improved disease specific survival (hazard ratio 0.17, P = 0.014) in early OSCC and could therefore be used as prognostic biomarker. Early OPSCCs showed more hypermethylation of CDH13 (58%), TP73 (14%), and total hypermethylated genes. Hypermethylation of two or more genes has a significantly different effect on survival in OPSCC compared with OSCC, with a trend toward worse instead of better survival. This could have a biological explanation, which deserves further investigation and could possibly lead to more stratified treatment in the future.     

Effects of functional training of dysphagia to prevent pneumonia for patients on tube feeding

Objective: The purpose of this study was to evaluate the effects of functional training on outbreak frequency of pneumonia for the elderly dysphagia patients who were being tube fed. Methods: Subjects were divided into two groups; one group (n = 10) received oral care (i.e. non‐training group) and the other group (n = 11) received functional training of dysphagia in addition to oral care (i.e. training group). The dental health team treated subjects once a week for 3 years (1999–2001). The frequency of pneumonia outbreaks and changes in activities of daily living scale (ADL) were evaluated for each year. Result: It was recognised that the frequency of pneumonia in the training group decreased year by year (p < 0.05). Cognitive items in ADL improved in two subjects of the training group. No statistical differences were recognised in the non‐training group. Conclusion: It was suggested that once‐a‐week functional training of dysphagia with professional oral care might be effective in preventing pneumonia for elderly people who were being tube fed.     

Surface architecture of the oropharyngeal cavity and the digestive tract of Mulloidichthys flavolineatus from the red sea,Egypt: A scanning electron microscope study

Surface architecture of the buccal cavity and the surface organization of the luminal mucosa of the oesophagus, stomach, and intestine of the carnivorous fish M. flavolineatus from the Red Sea were studied by using SEM. The results revealed that M. flavolineatus has four kinds of teeth; curved-blunt, wedge-shaped, flattened crowns, molariform and papilliform. Three types of taste buds (type I, II and III) were recorded in the oropharyngeal cavity. It was observed that taste buds and teeth are co-located in the pharyngeal region. Characteristic patterns of microridges of the surface cells in the oral cavity and oesophagus were observed. Mucous cells are distributed in the lining of the mouth cavity, oesophagus, stomach, and intestine. Characteristic patterns of mucosal folds throughout the alimentary canal, concerning oesophagus, stomach, and intestine were revealed. Numerous gastric pits, which represents the emergence of the gastric glands, were recorded in the anterior and middle regions of the stomach. Complex patterns of the folds and mucous cells were recorded in the intestinal mucosa. These results were discussed with other teleost fishes.     

Palliative radiotherapy and quality of life in patients with locally advanced thoracic esophageal cancer: a single centre experience from Central India

BackgroundPatients with locally advanced esophageal squamous cell carcinoma (LAESCC ) have decreased quality of life (QoL) and, thus, require palliative external beam radiotherapy (EBRT). The present study was performed to evaluate the QoL in patients with LAESCC undergoing palliative EBRT.Materials and methodsThis was a prospective, observational study performed over a period of 18 months (from December 2018 to May 2020) in the Department of Radiation Oncology. Seventy patients with LAESCC received EBRT (30 Gy in 10 fractions, at 3 Gy per fraction over 2 weeks). Patients were followed-up at monthly intervals for 3 months. The dysphagia and odynophagia scores were calculated at baseline and follow-up visits. The QoL was assessed with 18-item EORTC QLQ-OES questionnaire at baseline and 3 months.ResultsOver the study period, significant decrease in mean dysphagia and odynophagia score was observed (p-value < 0.0001). On post-hoc analysis, significant decrease in both dysphagia and odynophagia score was observed between baseline and at the end of study and between various follow-up visits (p-value < 0.0001). Moreover, there was a significant increase in mean body weight (p-value < 0.0001). At 3 months, there was a significant decrease in dysphagia (p-value < 0.0001), eating (p-value < 0.0001), reflux (p-value = 0.005), pain (p-value < 0.0001), and saliva (p-value = 0.01) domains of EORTC QLQ-OES18 questionnaire.ConclusionIn patients with LAESCC, EBRT leads to significant decrease in dysphagia and odynophagia, and increase in body weight. These changes indirectly lead to improved QoL.     

Coordinate Mapping of Hyolaryngeal Mechanics in Swallowing

Characterizing hyolaryngeal movement is important to dysphagia research. Prior methods require multiple measurements to obtain one kinematic measurement whereas coordinate mapping of hyolaryngeal mechanics using Modified Barium Swallow (MBS) uses one set of coordinates to calculate multiple variables of interest. For demonstration purposes, ten kinematic measurements were generated from one set of coordinates to determine differences in swallowing two different bolus types. Calculations of hyoid excursion against the vertebrae and mandible are correlated to determine the importance of axes of reference.To demonstrate coordinate mapping methodology, 40 MBS studies were randomly selected from a dataset of healthy normal subjects with no known swallowing impairment. A 5 ml thin-liquid bolus and a 5 ml pudding swallows were measured from each subject. Nine coordinates, mapping the cranial base, mandible, vertebrae and elements of the hyolaryngeal complex, were recorded at the frames of minimum and maximum hyolaryngeal excursion. Coordinates were mathematically converted into ten variables of hyolaryngeal mechanics.Inter-rater reliability was evaluated by Intraclass correlation coefficients (ICC). Two-tailed t-tests were used to evaluate differences in kinematics by bolus viscosity. Hyoid excursion measurements against different axes of reference were correlated. Inter-rater reliability among six raters for the 18 coordinates ranged from ICC = 0.90 - 0.97. A slate of ten kinematic measurements was compared by subject between the six raters. One outlier was rejected, and the mean of the remaining reliability scores was ICC = 0.91, 0.84 - 0.96, 95% CI. Two-tailed t-tests with Bonferroni corrections comparing ten kinematic variables (5 ml thin-liquid vs. 5 ml pudding swallows) showed statistically significant differences in hyoid excursion, superior laryngeal movement, and pharyngeal shortening (p < 0.005). Pearson correlations of hyoid excursion measurements from two different axes of reference were: r = 0.62, r² = 0.38, (thin-liquid); r = 0.52, r² = 0.27, (pudding).Obtaining landmark coordinates is a reliable method to generate multiple kinematic variables from video fluoroscopic images useful in dysphagia research.     

A let-7 microRNA polymorphism in the KRAS 3′-UTR is prognostic in oropharyngeal cancer

IntroductionThis study aimed to investigate the effect of genetic polymorphisms in miRNA sequences, miRNA target genes and miRNA processing genes as additional biomarkers to HPV for prognosis in oropharyngeal squamous cell carcinoma (OPSCC) patients. Secondarily, the prevalence of HPV-associated OPSCC in a European cohort was mapped.MethodsOPSCC patients (n = 122) were genotyped for ten genetic polymorphisms in pre-miRNAs (pre-mir-146a, pre-mir-196a2), in miRNA biosynthesis genes (Drosha, XPO5) and in miRNA target genes (KRAS, SMC1B). HPV status was assessed by p16 immunohistochemistry (IHC) and high-risk HPV in situ hybridization (ISH) or by p16 IHC and PCR followed by enzyme-immunoassay (EIA). Overall and disease specific survival were analysed using Kaplan–Meier plots (log-rank test). Cox proportional hazard model was used to calculate hazard ratios (HR).ResultsThe overall HPV prevalence rate in our Belgian/Dutch cohort was 27.9%. Patients with HPV⁺ tumours had a better 5-years overall survival (78% vs. 46%, p = 0.001) and a better 5-years disease specific survival (90% vs. 70%, p = 0.016) compared to patients with HPV⁻ tumours. In multivariate Cox analysis including clinical, treatment and genetic parameters, HPV negativity (HR = 3.89, p = 0.005), advanced T-stage (HR = 1.81, p = 0.050), advanced N-stage (HR = 5.86, p = 0.001) and >10 pack-years of smoking (HR = 3.45, p = 0.012) were significantly associated with reduced overall survival. The variant G-allele of the KRAS-LCS6 polymorphism was significantly associated with a better overall survival (HR = 0.40, p = 0.031).ConclusionsOur results demonstrate that OPSCC patients with the KRAS-LCS6 variant have a better outcome and suggest that this variant may be used as a prognostic biomarker for OPSCC.     

Single Nucleotide Polymorphisms May Increase the Risk of Aspiration Pneumonia in Post-Stroke Patients with Dysphagia

This study aimed to evaluate whether genetic polymorphism is associated with an increased risk of infection, specifically post-stroke aspiration pneumonia. Blood samples were obtained from a total of 206 post-stroke participants (males, n = 136; mean age, 63.8 years). Genotyping was performed for catechol-O-methyltransferase (rs4680, rs165599), dopamine receptors (DRD1; rs4532, DRD2; rs1800497, DRD3; rs6280), brain-derived neurotrophic factor (rs6265), apolipoprotein E (rs429358, rs7412), and the interleukin-1 receptor antagonist gene (rs4251961). The subjects were stratified into two groups, aged < 65 (young) and ≥ 65 (elderly). Functional parameters and swallowing outcomes were measured at enrollment and at 3 months post-onset. The primary outcome was the incidence of aspiration pneumonia. Analysis of the association between genetic polymorphisms and aspiration pneumonia history showed that a minor C rs429358 allele was associated with the occurrence of aspiration pneumonia in the young group, both in the additive and the dominant models (odds ratio: 4.53; 95% CI: 1.60–12.84, p = 0.004). In the multivariable analysis, the minor C rs429358 allele increased the risk of post-stroke aspiration pneumonia in young stroke patients by 5.35 (95% CI: 1.64–20.88). In contrast, no such association was observed in the elderly group. Apolipoprotein E polymorphism may affect the risk of post-stroke aspiration pneumonia.     

甲流患儿鼻咽部及口咽部的菌群分析

目的 比较甲流（IA）患儿鼻咽部及口咽部菌群与健康儿童的差异,分析甲型流感病毒（IAV）感染后可能对儿童鼻咽部及口咽部菌群的影响。方法 选取我院120例甲流患儿作为病例组,120例年龄性别相近的健康儿童作为健康组,采用高通量测序技术,对采集的所有鼻咽部及口咽部标本行16S rDNA基因测序分析,比较两组儿童间的菌群多样性及在门、属水平上菌群结构的差异。结果 病例组鼻咽部及口咽部的菌群多样性均高于对照组（Ps0.05）,病例组鼻咽部的变形菌门（Proteobacteria）相对丰度显著高于健康组（Ps<0.05）;在鼻咽部菌属水平上,病例组中正常优势菌莫拉氏菌属（Moraxella）、棒状菌属（Corynebacterium）、狡诈菌属（Dolosigranulum）、普氏菌属（Prevotella）等的相对丰度显著减少（Ps<0.05）,而链球菌属（Streptococcus）、嗜血杆菌属（Haemophilus）、盐单胞菌属（Halomonas）、不动杆菌属（Acinetobacter）、罗尔斯通菌属（Ralstonia）等的相对丰度显著增加（Ps<0.05）,叶杆菌属（Phyllobacterium）仅见于病例组;在口咽部菌属水平上,病例组菌群相对减少的有奈瑟菌属（Neisseria）、乳杆菌属（Lactobacillus）等,而葡萄球菌属（Staphylococcus）、奇异菌属（Atopobium）、放线菌属（Actinomyces）等的相对丰度显著增加（Ps<0.05）。结论 通过对甲流患儿进行上呼吸道菌群分析,揭示了甲流患儿鼻咽部及口咽部菌群的失调,这提示我们可从微生态角度研究甲流,从而进一步了解甲流的发病机制,为减少甲流严重并发症及病死率提供可能的理论依据。