Formulation and in-vivo evaluation of L-cysteine chewing gums for binding carcinogenic acetaldehyde in the saliva during smoking.

Cigarette smoke contains toxic amounts of acetaldehyde that dissolves in saliva, posing a significant risk of developing oral, laryngeal and pharyngeal carcinomas. L-cysteine, a non-essential amino acid, can react covalently with carcinogenic acetaldehyde to form a stable, non-toxic 2-methylthiazolidine-4-carboxylic acid. The main aim of this study was to find out whether it is possible to develop a chewing gum formulation that would contain cysteine in amounts sufficient to bind all the acetaldehyde dissolved in saliva during the smoking of one cigarette. The main variables in the development process were: (1) chemical form of cysteine (L-cysteine or L-cysteine hydrochloride), (2) the amount of the active ingredient in a gum and (3) manufacturing procedure (traditional or novel compression method). Saliva samples were taken over 2.5 minutes before smoking and since smoking was started for 2.5 minutes periods for 10 minutes. During a five minutes smoking period with a placebo chewing gum, acetaldehyde levels increased from 0 to 150-185 microM. Once smoking was stopped, the acetaldehyde levels quickly fell to levels clearly below the in-vitro mutagenic level of 50 microM. All chewing gums containing cysteine could bind almost the whole of the acetaldehyde in the saliva during smoking. However, elimination of saliva acetaldehyde during smoking does not make smoking completely harmless. Cysteine as a free base would be somewhat better than cysteine hydrochloride due to its slower dissolution rate. Both traditional and direct compression methods to prepare chewing gums can be utilized and the dose of L-cysteine required is very low (5 mg).

Tobacco carcinogen-detoxifying enzyme UGT1A7 and its association with orolaryngeal cancer risk.

BACKGROUND: UDP-glucuronosyltransferase 1A7 (UGT1A7) detoxifies several tobacco carcinogens. We determined whether UGT1A7 expression is observed in normal orolaryngeal tissue and whether UGT1A7 allelic variations are associated with the risk for orolaryngeal cancer. METHODS: UGT1A7 expression in normal orolaryngeal tissue was determined by semiquantitative reverse transcription-polymerase chain reaction (PCR). Buccal cell DNA isolated from 194 case subjects with orolaryngeal cancer and from 388 control subjects who were matched by sex, age, and race was subjected to UGT1A7 genotyping with the use of combined PCR-restriction fragment length polymorphism and allelic discrimination analysis. All statistical tests were two-sided. RESULTS: UGT1A7 messenger RNA was expressed at similar levels in the esophagus, tongue, tonsil, floor of the mouth, and larynx. Genotyping revealed the presence of three variant reduced-activity UGT1A7 alleles in both Caucasians and African-Americans. Individuals with any of the predicted low-activity UGT1A7 genotypes had an increased risk of orolaryngeal cancer (odds ratio [OR] = 3.7; 95% confidence interval [CI] = 1.7 to 8.7) relative to subjects with the wild-type genotype. Both Caucasians and African-Americans with the low-activity genotypes had statistically significantly increased orolaryngeal cancer risk compared with Caucasians and African-Americans with the wild-type genotype (OR = 2.8 [95% CI = 1.1 to 7.6] and OR = 6.2 [95% CI = 1.2 to 31], respectively). For subjects with the predicted low-activity genotypes, the risks of oral cavity cancer (OR = 4.2; 95% CI = 1.7 to 10) and laryngeal cancer (OR = 3.7; 95% CI = 0.99 to 14) were similar. There was no association between UGT1A7 genotype and orolaryngeal cancer risk in never smokers, whereas subjects with predicted low-activity UGT1A7 genotypes who were light smokers (OR = 3.7; 95% CI = 1.1 to 12) or heavy smokers (OR = 6.1; 95% CI = 1.5 to 25) had an increased risk. CONCLUSIONS: The tissue expression of UGT1A7 is consistent with the possibility of a physiologic role in orolaryngeal cancer. Variations in the UGT1A7 gene that reduce UGT1A7 activity may affect the risk of smoking-related orolaryngeal cancer.

Epidemiology of alcohol and cancer.

There is still insufficient knowledge of the distribution of drinking habits in human populations, and more descriptive surveys are needed. Both prospective and retrospective epidemiological studies indicate that alcohol consumption is a cancer hazard. Prospective studies on excessive drinkers have shown an increased risk for cancer of the mouth, pharynx, larynx, esophagus, liver, and lung. Retrospective studies have confirmed this excess risk. For cancers of the buccal cavity, pharynx, larynx, and esophagus, the effect of drinking has been shown to be associated with the effect of smoking. In the case of esophageal cancer, these two effects are independent, and the observations made are consistent with a multiplicative model. Primary liver cancer is also associated with alcohol consumption, probably by a less direct action; the importance of the impact of alcohol on primary liver cancer is probably underestimated. Animal experiments have not shown that ethanol alone has a carcinogenic effect, and the mechanisms by which alcoholic beverages act on humans remain unknown. The proportion of cancer cases at sites known to be associated with alcohol consumption is approximately 8% in most population groups in the United States. This indicates that a sizeable proportion of cancers is potentially preventable if appropriate action is taken.

Comparative epidemiology of tobacco-related cancers.

In a retrospective study, interviews were obtained with 3,716 patients with histologically proven cancer of the lung (Kreyberg types I and II), mouth, larynx, esophagus, or bladder and with over 18,000 controls. For each of these cancers, the relative risk of both male and female present smokers increased with the quantity smoked and the duration of the habit. The strongest increase occurred for cancer of the lung and larynx, and the least increase occurred for cancer of the esophagus and bladder. For exsmokers the risk decreased with years of cessation. The risk for mouth cancer of pipe and cigar smokers who inhaled much less than cigarette smokers was less than that of the latter and increased with the quantity smoked. The risk of mouth, larynx, and esophagus cancer among smokers increased with the quantity of alcohol consumed. Greater smoking habits and lesser cessation rates were noted among lower socioeconomic groups, suggesting that these groups will bear an ever increasing proportion of the burden of tobacco-related cancer.

Laryngeal Kaposi's Sarcoma Complicated by the Immune Reconstitution Inflammatory Syndrome in an HIV-infected Patient.

We herein report a case of laryngeal Kaposi's sarcoma (KS) complicated by immune reconstitution inflammatory syndrome in a human immunodeficiency virus (HIV)-infected patient. The patient initially presented with KS involving the larynx, which was successfully treated with pegylated liposomal doxorubicin (PLD) and antiretroviral therapy (ART). PLD was discontinued after 2 courses because of a marked clinical improvement; however, the patient experienced progressive odynophagia and dyspnea 2 months after the initiation of ART. Laryngoscopy revealed a severely swollen, inflamed epiglottis. The readministration of PLD was successful, and the patient was thereafter discharged without any subsequent complications.

Squamous cell carcinoma of the upper aerodigestive tract in exclusive smokers, chewers, and those with no habits.

BACKGROUND: Tobacco consumption is the major risk factor for developing head and neck squamous cell cancer (SCC). The site of development of HNSCC may depend on the way the tobacco is consumed. While laryngeal cancers are more common among smokers, oral cancers are more common among tobacco chewers. Since the use of smokeless tobacco is increasing, it is important to know whether this difference is restricted only to site wise distribution or it has other clinical and pathological implications. PATIENTS AND METHODS: We analyzed a prospectively collected dataset of HNSCC patients other than nasopharyngeal cancers attending our outpatient department at a single unit of the head and neck services at Tata Memorial Hospital, Mumbai, India, between January 2010 and September 2011. There were 747 eligible patients and were divided into three groups: Those with chewing as the only habit (chewers), those with smoking as the only habit (smokers), and those with no habits. Patients with regular use of alcohol were excluded from the study. The clinical and pathological parameters were analyzed. RESULTS: Of the 747 patients, the tobacco chewers formed 69.3% followed by smokers (19.5%) and patients with no habits (11.1%). Majority of smokers were men (98%). Site distribution revealed patients with chewing as the only habit had oral cancers (most commonly gingivobuccal complex cancers) as the most common site and those with smoking as the only habit had larynx as the most common site. In patients with no habits, oral tongue was found to be the most common site. No statistically significant pathological differences were observed in between these groups in patients who underwent surgery (n = 366) at the initial modality of treatment. CONCLUSIONS: There is a direct relationship between the form of tobacco use and site of appearance of HNSCC. However, there are no differences in clinical or pathological parameters between HNSCC caused by tobacco chewing or tobacco smoking.

Occupation and upper aerodigestive tract cancers: a follow-up study in Sweden.

OBJECTIVES: We sought to examine the associations between occupation and upper aerodigestive tract cancers at various anatomic sites. METHODS: The Swedish Family-Cancer Database was used to calculate standardized incidence ratios for different occupational groups, adjusted for age, period, and socioeconomic status. RESULTS: Male dentists showed an increased risk for tongue cancer; hairdressers had an increased risk for tongue and larynx cancers among men and pharynx cancer among women; launderers and dry cleaners showed an increased risk for pharynx cancer among men and lip cancer among women; outdoor occupations such as fishermen, seamen, transport, and construction workers showed increased risks for lip cancer. CONCLUSIONS: Although smoking and alcohol drinking can explain some of these results, increased risks found for dentists, hairdressers, and launderers and dry cleaners may partly be explained by their work-related exposures; increased risks of lip cancer in outdoor occupations can be explained by sunlight exposure.

Teflonomas of the larynx and neck.

Intracordal fluorocarbon (Teflon, Mentor O and O Inc, Norwell, MA) injection has been used for decades to correct paralytic dysphonia, a result of unilateral laryngeal paralysis. Infrequently, the Teflon extravasates and infiltrates into the soft tissues of the neck and larynx producing a mass that clinically simulates a malignant lesion. We report eight cases of so-called "Telonomas" of the larynx and neck that have been identified in the files of the Armed Forces Institute of Pathology Otolaryngic Tumor Registry and from the Cytopathology Service at the George Washington University Medical Center. Patients ranged in age from 31 to 72 years. Vocal cord paralysis, treated by Teflon injection, was caused by primary laryngeal carcinoma or metastatic carcinoma (breast, lung) involving the recurrent laryngeal nerve, surgical trauma to the recurrent laryngeal nerve, or postviral neuritis. Subsequent symptomatology, related to extravasation of the Teflon with a resulting "Teflonoma", included a neck mass or persistent hoarseness. Infrequently, there was associated airway obstruction or voice changes. Diagnosis was made by fine needle aspiration or by excision of the suspicious mass and subsequent identification of a foreign body granulomatous reaction with associated birefringent material. Infrared absorption spectrophotometry identified the foreign material as a fluorocarbon which was further substantiated by scanning electron microscopy and energy dispersive x-ray analysis. Surgical removal of the mass alleviated all symptoms.

Mortality from alcohol related disease in Italy.

Trends in death certification rates from the five major alcohol related causes of death in Italy (cancers of the mouth or pharynx, oesophagus, larynx, liver and cirrhosis of the liver) were analysed over a period (1955-79) in which per capita alcohol consumption almost trebled. Age standardised mortality from liver cirrhosis almost doubled in males and increased over 70% in females. In males, mortality from cancers of the upper digestive or respiratory tract showed increases of between 27% and 44%, and liver cancer increased by over 100%. In the late 1970s, the four alcohol related cancer sites accounted for about 12% of all cancer deaths in males and 4.5% in females. Mortality from liver cirrhosis alone accounted for 4.8% of all deaths in males (9.2% of manpower years lost) and 2.3% in females (6.3% manpower years lost) in females. These figures were even higher in selected areas of north eastern Italy, where alcohol consumption is greater. In absolute terms, the upward trends observed correspond to about 10,000 excess deaths per year in the late 1970s compared with rates observed two decades earlier and are thus second only to the increase in tobacco related causes of death over the same calendar period.

Upper airway complications of smoking.

Tobacco smoke has a myriad of acute and chronic effects on the upper airway. These problems can range from aggravating inflammatory reactions to life threatening malignancies. Cessation of smoking is the key to successful resolution of many upper airway complaints. An increased awareness of these disease processes can improve early diagnosis and appropriate treatment. A better awareness of these processes may facilitate physicians in counseling patients about smoking.

Relationship between dental factors and risk of upper aerodigestive tract cancer.

We examined the relationship between dental health variables and risk of upper aerodigestive tract (UADT) cancers in a case-control study in Southern Brazil. The study population included 717 cases of cancers of the mouth, pharynx, and larynx and 1434 controls matched on age, gender, period of admission and study site. The association with dental factors was investigated by conditional logistic regression using extensive adjustment for a priori and empirical confounders, including tobacco and alcohol consumption, diet and sociodemographic variables. Lifetime use of dentures was not associated with risk of any UADT cancer, but history of oral sores secondary to ill-fitting dentures was associated with cancers of the mouth (odds ratio [OR] = 2.3, 95% confidence interval [CI] 1.2-4.6) and of the pharynx (OR = 2.7, 95% CI 1.1-6.2) among those using dentures. The association for mouth cancers was restricted primarily to an increased risk of tongue neoplasms (OR = 9.1, 95% CI 1.9-43.4). Less than daily tooth brushing frequency was also associated with risk of cancer of the tongue (OR = 2.1, 95% CI 1.0-4.3) and of other parts of the mouth (OR = 2.4, 95% CI 1.0-5.4). Having broken teeth was not significantly associated with risk of UADT cancer of any site. We conclude that poor oral hygiene due to infrequent tooth brushing and sores caused by dentures are risk factors for cancer of the mouth and that these associations are unlikely to be due to insufficient control of confounding.

Alcohol and tobacco consumption in cancer of the mouth, pharynx, and larynx: a study of 316 female patients.

Three hundred sixteen female patients with cancer of the larynx, pharynx, and mouth were examined and the following cancer sites were compared with respect to alcohol and tobacco consumption: oropharynx, hypopharynx, larynx, epilarynx, lip, and mouth. The mean daily tobacco consumption of smokers and ex-smokers was not significantly different between cancer locations; however, significant differences between cancer sites were observed with regard to the proportion of nonsmokers. The percentage of nonsmokers was the highest for cancer of the lips and the lowest for cancer of the epilarynx. Cancer locations differed significantly depending on daily alcohol consumption. Consumption was the lowest for patients with cancer of the lips. The percentage of nondrinkers was high for cancers of the lips and larynx and low for cancer of the epilarynx. Examination of the nonsmoking/nondrinking females (27.2%) did not reveal any features specific to this group, except that the patients were older.

Epidemiology of head and neck cancer.

The epidemiology of head and neck cancer can be accounted for largely in terms of known carcinogens introduced into the body through the mouth. Though there are many environmental exposures--such as asbestos, radon, nickel and arsenic--which have strong carcinogenic effects, most of these have only a small impact on the general population because exposure is limited, usually to small occupational groups. Two prevalent exposures, however, tobacco and alcohol, are strong risk factors for nearly all sites in the head and neck, and together account for about 80%-90% of all cancers of the head and neck. There is evidence for biologic interaction between some occupational exposures and cigarette smoking for cancer of the lung, and tobacco and alcohol for cancer of the mouth. Based on this evidence for biologic interaction and the prevalence of smoking, it seems likely that tobacco is related to about 80% of all cancers of the head and neck in the United States.

Papillomas of the larynx and pharynx: two case reports.

Two unusual cases of papillomas are presented: the first is that of a young boy with extensive papillomas of the larynx who was treated successfully without tracheotomy using endolaryngeal surgery and steroids at the time of each procedure. This case adds to the clinical evidence that the most probable cause of juvenile papillomas is a virus, since the mother had condyloma acuminata during pregnancy and at term. The second case is that of a young girl with rapidly recurring papillomas of the mouth and pharynx who was treated successfully with an autogenous vaccine and cryosurgery after other measures failed. This case demonstrates the effectiveness of cryosurgery in the treatment of papillomas and the possible efficacy of the autogenous vaccine suggests a viral etiology for papillomas of the pharynx and larynx.

E.N.T. manifestations of Von Recklinghausen's disease.

Von Recklinghausen's Disease (VRD) is a neurocutaneous, systemic disease characterized by CNS tumors and disorders, cafe-au-lait spots, generalized cutaneous neurofibromata, skeletal deformities, and somatic and endocrine abnormalities. It is an autosomal dominant, hereditary disorder found in approximately 1:2500 to 3300 births. There are many manifestations of this disease in the head and neck region of interest to the otolaryngologist. Case reports of three patients with multiple ENT involvements are detailed. A review of the literature is presented with a brief discussion of diagnosis and treatment. The most common intracranial tumor in the adult is the acoustic neuroma, usually bilateral, while in the child it is the astrocytoma. A defect in the sphenoid bone is common and may produce temporal lobe herniation into the orbit causing pulsatile exophthalmos. Involvement of the facial bones usually causes radiolucent defects secondary to neurofibromata within nerve pathways, and a variety of asymmetrical changes, especially within the mandible. "Elephantiasis" of the face is a hypertrophy of the soft tissues overlying a neurofibroma, often quite extensive and disfiguring. Laryngeal and neck involvement may compromise the airway and early and repeated surgical intervention is required. The over-all malignancy rate approaches 30%, indicating that the patient with VRD may be predisposed to developing a malignancy. There appears to be an increased surgical risk in these patients, with some demonstrating abnormal responses to neuromuscular blockade.

Dental status and oral hygiene in patients with head and neck cancer.

Poor oral hygiene is believed to play a role as a risk factor for head and neck cancer, especially for oral cancer. Only few epidemiologic data exist about dental status and oral hygiene in these patients. We performed a case-control study involving 100 patients with squamous cell carcinoma of the upper aerodigestive tract and 214 age- and sex-matched control subjects with no known tumorous disease. In the tumor patients, oral hygiene and dental status proved to be significantly worse: the majority of the tumor patients seldom or never brushed their teeth and the frequency of dental visits was significantly lower. Tartar of 3 mm or more was found in 40.9% of the tumor patients and in 22% of the control subjects. In the tumor group, the incidence of decayed teeth was significantly higher compared with the control subjects. Chronic inflammation of the gingiva was observed in 28% of the tumor patients vs. 13.5% in the control group. Oral hygiene was negatively correlated with alcohol as well as with tobacco consumption. The social status of subjects also correlated with oral hygiene, which was found to be worst in subjects from the lower social strata. The present study revealed a poor dental status and oral hygiene in patients with head and neck cancer. The pathogenetic mechanism being associated with this suspected risk factor remains to be investigated.

Alcohol-related cancers in Mediterranean countries.

In most countries bordering the Mediterranean, alcohol ranks second to tobacco as a risk factor for cancer. It is directly implicated in cancer of the mouth, larynx, hypopharynx and esophagus. For all these cancers a dose-response relationship has been demonstrated as well as a combination with the effect of tobacco, the two effects being multiplicative. Alcohol is also responsible for liver cancer developing on alcoholic cirrhosis. In addition, it has been suggested that alcohol consumption may be related to an increased risk of breast cancer.

Co-carcinogenesis and field cancerization: oral lesions offer first signs.

This article describes two cases of multifocal synchronous cell squamous cell carcinoma in high-risk patients. The initial presentation in both instances was an erythroplakic oral lesion. The importance of the team approach between the dentist and the oncologist for quality patient care is underscored.

Hoarseness: a potential role for the dentist in early diagnosis.

A patient who smoked heavily was under regular review by the oral medicine department because of oral keratosis. He subsequently complained of hoarseness of the voice, and was referred to the department of otorhinolaryngology. An early squamous cell carcinoma of the larynx was diagnosed, and the patient was treated with radical radiotherapy. This case highlights the importance of early diagnosis and the potential role of the dentist in the total healthcare of patients.

[Occupational exposure in cancer of the mouth, pharynx and larynx]. / Exposición ocupacional en el cáncer oral, faríngeo y laríngeo.

The AA. have scheduled a case-control study in order to assess the ambient hazards factors in these cancers, through the evaluation of its occupational risk. The program cover 242 cases of the epidermoid type of carcinoma (positive biopsy), and the group was parallelled with another group of 322 (after the age) admitted at the same Hospital, but affected with several processes. Were excluded the cancer of the lung, bladder, pancreas and kidney because of the causal link with tobacco smokers. In oral and pharyngeal cancer the AA. found out that the workers of high risk were butchers, blacksmiths, masons, drivers, electricians and railwaymen. Regarding the cancer of the larynx mechanics, plumbers, farmers, textile workers and drivers showed the greatest linkage. These findings are in accordance with those published in previous papers.