22 research outputs found
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
The “New” Head and Neck Cancer Patient—Young, Nonsmoker, Nondrinker, and HPV Positive: Evaluation
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
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Tobacco toxicant exposure in cigarette smokers who use or do not use other tobacco products.
BackgroundNon-cigarette other tobacco products (OTP; e.g., cigarillos, little cigars) are typically used in combination with cigarettes, but limited data exists on the tobacco toxicant exposure profiles of dual cigarette-OTP (Cig-OTP) users. This study examined biomarkers of nicotine and carcinogen exposure in cigarette smokers who used or did not use OTP.Methods111 Cig-OTP and 111 cigarette only (Cig Only) users who smoked equivalent cigarettes per day were matched on age (< 40, >=40), race (African American, White), and gender. Participants reported past 7-day daily use of cigarettes and OTP and provided urine for nicotine, cotinine, total nicotine equivalents (TNE) and total NNAL concentrations.ResultsCig-OTP users reported greater past 7-day tobacco use (15.9 versus 13.0 products/day, p<0.01) but had significantly lower creatinine-normalized nicotine (606 versus 1301ng/mg), cotinine (1063 versus 2125ng/mg), TNE (28 versus 57 nmol/mg) and NNAL (251 versus 343pg/mg) than Cig Only users (p<0.001).ConclusionsCig-OTP users had lower levels of nicotine and metabolites of a lung carcinogen relative to Cig-Only users, but concentrations of toxicants among Cig-OTP users were still at levels that place smokers at great risk from the detrimental health effects of smoking.ImpactOur study finds that nicotine and carcinogen exposure in Cig-OTP users are lower compared to cigarette only users, but still likely to be associated with substantial harm. A better understanding of why toxicant levels may be lower in Cig-OTP is an important area for future study
Analysis of Alkaloids in Areca Nut-Containing Products by Liquid Chromatography–Tandem Mass Spectrometry
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
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]Âthymidine
(<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]Âguanine
(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.
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 <.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
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