Elevated levels of 1-hydroxypyrene and NOe-Nitrosonornicotine in the urine of smokers with head and neck cancer: a matched control study

University of Minnesota M.S. thesis. April 2014. Major: Clinical Research. Advisor: Dorothy Hatsukami. 1 computer file (PDF); vi, 26 pages.Background: Head and neck squamous cell carcinoma (HNSCC) is associated with tobacco use. Still, most smokers do not develop HNSCC. The mechanisms of varying susceptibility to HNSCC are poorly studied to date. Tobacco metabolite research provides insight regarding the innate metabolism and excretion of carcinogens. Methods: Smokers with HNSCC (cases) were compared to smokers without HNSCC (controls) in a matched cohort. The tobacco metabolites studied are: 1-hydroxypyrene (1-HOP), Nf-nitrosonornicotine (NNN), and 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL). Results: In 33 subjects, mean 1-HOP was 1.82 pmol/mg creatinine vs 1.08 pmol/mg creatinine (p=0.004) and mean NNN was 0.10 pmol/mg creatinine vs 0.04 pmol/mg creatinine (p=0.01) in cases and controls, respectively. NNAL did not differ between groups. Conclusions: Smokers with HNSCC have elevated urinary levels of 1-HOP and total NNN compared to matched controls suggesting an increased effective exposure to these carcinogens. Tobacco constituent metabolites may be useful in understanding tobacco-related carcinogenesis in HNSCC

Smokeless tobacco use: pattern of use, knowledge and perceptions among rural Bangladeshi adolescents

Background: The aim of the study was to investigate the practice and pattern of smokeless tobacco (SLT) use as well as the knowledge and perception about its ill effects among rural Bangladeshi adolescents. Methods: A cross-sectional survey was conducted among students aged 13–18 years in two rural secondary schools in Bangladesh in August 2015. Data were collected through a self-administered questionnaire which consists of topics derived from the Social Cognitive Theory and Health Belief Model (personal characteristics, environmental factors, self-efficacy, outcome expectancies, perceived susceptibility, perceived severity, perceived benefits, perceived barriers, and cues to action). Data analysis was performed using SPSS version 24. A descriptive analysis was conducted to determine the current pattern of SLT use and knowledge about its ill effects. A chi-square test and Fisher exact test were conducted to explore associations between variables. Lastly, a logistic regression model was used to locate the predictors for current SLT use. Results: A total of 790 students participated in the study. Among them, 9.5% (75) had used SLT at least once and 3.7% (29) were current SLT users. Males had a higher incidence of SLT use compared with females. The majority of students (77.3%) initiated SLT use between 10–13 years of age. ‘Zarda’ was the most common type of SLT used and most of the current users (86%) were able to buy SLT without age restrictions. Most of the current users (90%) wanted to quit SLT immediately; however, professional help was not available in schools. Overall, students had a good knowledge about the harmful effects of SLT with 54.8% (428) of respondents scoring in the good knowledge category. However, the majority of never SLT users (55.4%; 396) had a good knowledge compared to ever SLT users (42.7%; 32). Significant predictors of current SLT use included being a student aged 14 years and above (OR = 6.58, 95% CI [2.23–28.31]) as well as the variables of self-efficacy (OR = 5.78, 95% CI [1.46–19.65]), perceived barriers (OR = 0.30, 95% CI [0.10–0.74]), perceived benefit (OR = 0.21, 95% CI [0.05–1.03]) and perceived severity (OR = 0.36, 95% CI [0.16–0.91]). Discussion: This study demonstrates the need for comprehensive prevention and control programme in rural schools targeting young adolescents. Effective measure should be taken to reshape the attitude of rural adolescents towards self-confidence and competence, as to prevent SLT use

Oral/oropharyngeal “selfies” in gay and bisexual men: a pilot study exploring oropharyngeal screening for HPV-related possible malignancies

ObjectivesThis study aims to determine the potential uptake and quality of oropharyngeal “selfies” taken by gay/bisexual men as a screening approach for HPV-associated oropharyngeal cancer.MethodsFrom 1,699 gay/bisexual men in the US, surveyed about knowledge and attitudes to HPV-associated oropharyngeal cancer, a random sample of 320 men were invited to take an oropharyngeal “selfie” by smartphone and send it to the study website: 113 (35.5%) did so. Images were rated for quality by three healthcare professional raters blinded to each other's rating, with an otolaryngologist as the gold standard. In the second wave, those whose images were rated as unacceptable were sent a short instructional video and asked to send another image. Of the 65 invited, 46 did so. An additional 15.2% sent acceptable images, and a total of 28.3% of the sample was acceptable.ResultsA total of 1,121 men willing to participate in the future study who believed they could take a quality “oral selfie” were potentially eligible for this activity. A random sample of 320 participated: 153 participants started (47.8%) and 113 participants (35.3%) submitted an image. Responders were more likely to be younger, have higher knowledge scores on oropharyngeal HPV-related cancer, and have had HPV vaccination. There was high agreement between the three raters. Images of good/acceptable quality were 22.1%; oropharynx partially occluded images were 29.2%; oropharynx not visible images were 18.6%; images too dark were 21.2%; and images too small were 8.8%. From the second wave of requests with instructional videos, an additional 15.2% sent in quality images, with the remaining issues being partial occlusion of the tonsils by the tongue.ConclusionOne-third of the invited gay and bisexual men sent oropharyngeal selfie images to the study website and a total of 28.3% were of clinically acceptable quality. Following an instructional video on poorer-quality images, additional quality images were received. One barrier, i.e., partial occlusion of the oropharynx by the tongue remained. Quality oropharyngeal “selfies” are obtainable online

Laryngeal Transplantation: Research, Clinical Experience, and Future Goals

The loss of a functional voice because of trauma or laryngectomy can have a devastating impact on a patient's self-esteem and overall quality of life. Unfortunately, even with advances in organ preservation therapy, total laryngectomy is frequently necessary in the treatment of laryngeal carcinoma. Over the past several years, the senior author initiated research into laryngeal transplantation with the goal of restoring lung-powered speech for these patients. The research led to the development of an animal model and several groundbreaking studies in this area. Investigations into the use of irradiation, single-drug and multidrug immunosuppression, and the effects of mammalian target of rapamycin (mTOR) inhibitors have produced significant insight into laryngeal allograft preservation. The laboratory research culminated in the first successful total laryngeal transplant in 1998. The patient had suffered significant laryngeal trauma and strongly desired return of laryngeal phonation. The patient has been maintained on multidrug immunosuppression with minimal difficulties. Now more than 8 years after the procedure, the patient continues to have an excellent voice and dramatically improved quality of life. Recent data suggest that altered immunosuppression schedules and the use of mTOR inhibitors may allow patients to minimize immunosuppression-related adverse effects and ameliorate the risk of developing recurrent or de novo carcinoma. These data, when considered in combination with the progress made over the past 14 years, lead us to believe that the future of laryngeal transplantation is bright

Primary calcitonin-secreting neuroendocrine carcinoma of the larynx - Case report and update on current terminology

Primary calcitonin-secreting neuroendocrine carcinoma of the larynx is a rare neuroectodermal neoplasm currently classified as moderately differentiated (atypical carcinoid/WHO classification) neuroendocrine carcinoma of the larynx. Due to the rarity of these tumors at this location as well as their distinctive histologic and immunophenotypic features, they often raise significant diagnostic difficulties in biopsy specimens. We present a 57-year-old woman with persistent and gradually worsening pharyngeal pain for approximately one year duration, who was found to have a lesion limited to the right aryepiglottic fold. Final pathology showed moderately differentiated neuroendocrine carcinoma. Due to calcitonin positivity and coexistence of a thyroid nodule, the tumor raised the differential diagnosis of medullary thyroid carcinoma. A practical approach to pathologic diagnosis of laryngeal neuroendocrine tumors and discussion of clinical management is provided