22 research outputs found

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

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    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

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    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

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    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

    The “New” Head and Neck Cancer Patient—Young, Nonsmoker, Nondrinker, and HPV Positive: Evaluation

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    ObjectiveThe near epidemic rise of the incidence of human papillomavirus (HPV)-related oropharyngeal squamous cell carcinomas (OPSCC) presents the practitioner with a "new" head and neck cancer patient, vastly different from those with the traditional risk factors who formed the basis of most practitioners' training experience. Accordingly, a thorough and disease-specific evaluation process is necessitated. This article will review the evaluation of the HPV-related cancer patient, including a review of the HPV-positive oropharyngeal cancer epidemic from the surgeon's perspective, evaluation of the primary lesion, evaluation of the neck mass, and role of imaging, to provide a framework for addressing the challenging questions patients may ask.Data sourcesAvailable peer-reviewed literature and practice guidelines.Review methodsAssessment of selected specific topics by authors solicited from the Head and Neck Surgery and Oncology Committee of the American Academy of Otolaryngology-Head and Neck Surgery Foundation and the American Head and Neck Society.Conclusions and implications for practiceThe dramatic rise in OPSSC related to HPV is characterized by a "new" cancer patient who is younger and lacks traditional risk factors. Today's caregiver must be prepared to appropriately evaluate, counsel, and treat these patients with HPV-positive disease with the expectation that traditional treatment algorithms will evolve to maintain or improve current excellent cure rates while lessening treatment related side effects

    Analysis of Alkaloids in Areca Nut-Containing Products by Liquid Chromatography–Tandem Mass Spectrometry

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    Chewing of areca nut in different forms such as betel quid or commercially produced pan masala and gutkha is common practice in the Indian subcontinent and many parts of Asia and is associated with a variety of negative health outcomes, particularly oral and esophageal cancers. Areca nut-specific alkaloids arecoline, arecaidine, guvacoline, and guvacine have been implicated in both the abuse liability and the carcinogenicity of the areca nut. Therefore, variations in the levels of areca alkaloids could potentially contribute to variations in addictive and carcinogenic potential across areca nut-containing products. Here, we developed an accurate and robust liquid chromatography–tandem mass-spectrometry (LC–MS/MS) method for simultaneous quantitation of all four areca alkaloids and applied this method to the analysis of a range of products obtained from India, China, and the United States. The results of the analyses revealed substantial variations in the levels of alkaloids across the tested products, with guvacine being the most abundant (1.39–8.16 mg/g), followed by arecoline (0.64–2.22 mg/g), arecaidine (0.14–1.70 mg/g), and guvacoline (0.17–0.99 mg/g). Substantial differences in the relative contribution of individual alkaloids to the total alkaloid content were also observed among the different products. Our results highlight the need for systematic surveillance of constituent levels in areca nut-containing products and a better understanding of the relationship between the chemical profile and the harmful potential of these products

    Quantitation of Pyridyloxobutyl-DNA Adducts in Tissues of Rats Treated Chronically with (<i>R</i>)- or (<i>S</i>)‑<i>N</i>′‑Nitrosonornicotine (NNN) in a Carcinogenicity Study

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    We quantified DNA adducts resulting from 2′-hydroxylation of enantiomers of the tobacco-specific nitrosamine <i>N</i>′-nitrosonornicotine (NNN) in tissues of male F-344 rats after 10, 30, 50, and 70 weeks of treatment with 14 ppm in the drinking water. These rats were in subgroups of a carcinogenicity study in which (<i>S</i>)-NNN was highly tumorigenic in the oral cavity and esophagus, while (<i>R</i>)-NNN was relatively weakly active. DNA adducts were quantified by liquid chromatography–electrospray ionization–tandem mass spectrometry in six tissues: oral mucosa, esophageal mucosa, nasal respiratory mucosa, nasal olfactory mucosa, liver, and lung. <i>O</i><sup>2</sup>-[4-(3-Pyridyl)-4-oxobut-1-yl]­thymidine (<i>O</i><sup>2</sup>-POB-dThd, <b>7</b>) and 7-[4-(3-pyridyl)-4-oxobut-1-yl]-2′-deoxyguanosine (7-POB-dGuo, <b>8</b>), the latter as 7-[4-(3-pyridyl)-4-oxobut-1-yl]­guanine (7-POB-Gua, <b>11</b>), were detected at each time point in each tissue. In the target tissues for carcinogenicity, oral mucosa and esophageal mucosa, levels of 7-POB-Gua (<b>11</b>) and <i>O</i><sup>2</sup>-POB-dThd (<b>7</b>) were similar, or <b>11</b> predominated, while in all other tissues at all time points for both enantiomers, <b>7</b> was clearly present in greater amounts than <b>11</b>. Total measured DNA adduct levels in esophageal mucosa and oral mucosa were higher in rats treated with (<i>S</i>)-NNN than (<i>R</i>)-NNN. The highest adduct levels were found in the nasal respiratory mucosa. DNA adducts generally persisted in all tissues without any sign of substantial decreases throughout the 70 week time course. The results of this study suggest that inefficient repair of 7-POB-dGuo (<b>8</b>) in the rat oral cavity and esophagus may be important in carcinogenesis by NNN and support the development of these DNA adducts as potential biomarkers of NNN metabolic activation in people who use tobacco products

    Cotinine and tobacco-specific carcinogen exposure among nondaily smokers in a multiethnic sample.

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    BackgroundNondaily smoking has increased among current U.S. smokers during the past decade and is practiced by a significant percentage of smokers. Although research in nondaily smoking has grown, little is known about levels of exposure to tobacco toxicants among nondaily smokers and their variation across ethnic groups.MethodsWe examined urinary levels of cotinine and a tobacco-specific nitrosamine (NNAL) in community participants. Associations between the biomarker data and smoking characteristics were evaluated with Spearman's correlation analysis.ResultsParticipants included 28 Blacks, 4 Latinos, and 25 Whites who smoked at least 1 cigarette on 4-24 days in the past 30 days. Participants averaged 3.3 (SD = 2.1) cigarettes per day (cpd) on days smoked, they smoked an average of 13.0 (SD = 5.4) days in the past month, and they smoked nondaily for 10.5 (SD = 10.5) years. Median levels of creatinine-normalized cotinine and NNAL were 490.9 ng/mg and 140.7 pg/mg, respectively. NNAL and cotinine were highly correlated (r = .84); NNAL and cotinine were modestly correlated with cpd (r = .39 and r = .34; all p values &lt;.05). The number of days smoked per month was not associated with any biomarker levels.ConclusionsOur findings demonstrate that nondaily smokers are, on average, exposed to significant levels of nicotine and carcinogenic nitrosamines, with exposures of 40%-50% of those seen in daily smokers. This level of exposure suggests a significant health risk. Nicotine and carcinogen exposure is most closely related to number of cigarettes smoked per day but not to number of days per month of smoking

    Optimized Liquid Chromatography Nanoelectrospray–High-Resolution Tandem Mass Spectrometry Method for the Analysis of 4‑Hydroxy-1-(3-pyridyl)-1-butanone-Releasing DNA Adducts in Human Oral Cells

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    Metabolic activation of the carcinogenic tobacco-specific <i>N</i>-nitrosamines leads to the formation of 4-hydroxy-1-(3-pyridyl)-1-butanone (HPB)-releasing DNA adducts. We recently developed a liquid chromatography (LC)–tandem mass spectrometry (MS/MS) method for the analysis of HPB-releasing DNA adducts in human oral cells. However, given the limited amounts of DNA that can be extracted from oral cells, higher sensitivity and selectivity are required for the reliable analysis of these adducts in future studies. We have developed a new sensitive LC–nanoelectrospray ionization–high-resolution MS/MS method for the analysis of HPB-releasing DNA adducts in oral cells. A new procedure was also developed for guanine analysis by LC–MS/MS. The detection limit of the developed assay is 5 amol, and the limit of quantitation is 0.35 fmol HPB on-column, starting with 50 pg of DNA. The method was tested by analyzing oral samples from 65 smokers, including 30 head and neck squamous cell carcinoma (HNSCC) patients and 35 cancer-free controls. In all smokers, the levels of HPB-releasing DNA adducts averaged 6.22 ± 16.18 pmol/mg DNA, with significant interindividual variation being consistent with previous reports. The median HPB-releasing DNA adduct level was 6.6 times greater for those with HNSCC than for smokers without HNSCC (<i>p</i> = 0.002). The developed highly sensitive and selective method is a valuable tool for future measurement of HPB-releasing DNA adducts in tobacco users, which can potentially provide critical insights for the identification of individuals at risk for cancer
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