9/30/2004 PITTSBURGH, PA William S. Saunders et al. University of Pittsburgh Medical Center The amount of smoke in just one or two puffs of a cigarette can cause breaks in DNA and defects to a cell's chromosomes, leading to irreversible changes in genetic information being passed to a newly divided cell, according to University of Pittsburgh researchers. Their findings, to be reported Tuesday, Oct. 5 at the 35th Annual Meeting of the Environmental Mutagen Society, are the first to show that cigarette smoke causes chromosome instability. While most research has focused on the changes in DNA sequence caused by cigarette smoke, little attention has been given to how smoke affects genomic stability of cells. In laboratory studies using human fibroblasts, common cells found in connective tissue, William S. Saunders, Ph.D., and colleagues discovered that exposure to even a small amount of cigarette smoke condensate – equal to about 1/25 of a cigarette – caused breaks to both strands of DNA and compromised the integrity of the cell's chromosomes. Cigarette smoke contains some 5,000 organic compounds, including chemicals known to cause cancers. While the researchers did not expose cells to actual puffs of smoke, the cigarette smoke condensate they used was derived from burning real cigarettes and obtained from the R.J. Reynolds Tobacco Company. Containing mostly particulates, the extracted smoke was liquefied as part of a solvent mixture before it was exposed to the cells. "Double-stranded breaks are considered the most mutagenic type of DNA damage because the broken ends can [...]

9/29/2004 Chicago, IL no attribution Journal of the American Dental Association The Journal of the American Dental Association reported in its August edition that cigarette smoke combined with healthy saliva creates a mixture that can accelerate oropharyngeal cancer, according to researchers in the July 5 issue of British Journal of Cancer. The report outlined that saliva contains antioxidants molecules that fight and neutralize harmful substances and help protect the body against cancer. Researchers examined its role in the development of oral cancer by recreating the effects of cigarette smoke on cancerous cells of the mouth. They exposed one-half of cancerous cell samples to cigarette smoke alone and the other one-half to a saliva and cigarette smoke mixture. They used cancerous cells in their study to assess quickly whether the saliva and smoke mixture would speed the cancer development. Researchers found that cigarette smoke destroyed the antioxidants in the saliva and turned the saliva into a chemical mixture that could accelerate the development of mouth cancer. The longer the cancerous cells were exposed to the contaminated saliva, the more the cells were damaged. "Most people will find it very shocking that the mixture of saliva and smoke is actually more lethal to cells in the mouth than cigarette smoke alone", said study co-author Dr. Rafi Nagler. "Our study shows that once exposed to cigarette smoke, our normally healthy saliva not only loses its beneficial qualities but it turns traitor and actually aids in destroying the cells of the mouth and oral [...]

9/29/2004 Jean-François Daisne, MD, Thierry Duprez et al Radiology 2004;233:93-100 Purpose To compare computed tomography (CT), magnetic resonance (MR) imaging, and fluorine 18 fluorodeoxyglucose (FDG) positron emission tomography (PET) for delineation of gross tumor volume (GTV) in pharyngolaryngeal squamous cell carcinoma and to validate results with the macroscopic surgical specimen when available. MATERIALS AND METHODS Twenty-nine patients with stages II–IV squamous cell carcinoma treated with radiation therapy or chemotherapy and radiation therapy (n = 20) or with total laryngectomy (n = 9) were enrolled. Ten patients had oropharyngeal, 13 had laryngeal, and six had hypopharyngeal tumors. CT, MR imaging, and PET were performed with patients immobilized in a customized thermoplastic mask, and images were coregistered. GTVs obtained with the three modalities were compared quantitatively and qualitatively. If patients underwent total laryngectomy, images were validated with the surgical specimen after three-dimensional coregistration. The effect of each modality was estimated with linear mixed-effects models. Adjustments for multiple comparisons were made with the Bonferonni or Sidak method. RESULTS For oropharyngeal tumors and for laryngeal or hypopharyngeal tumors, no significant difference (P > .99) was observed between average GTVs delineated at CT (32.0 and 21.4 cm3, respectively) or MR imaging (27.9 and 21.4 cm3, respectively), whereas average GTVs at PET were smaller (20.3 [P .10] and 16.4 cm3 [P .01], respectively). GTVs from surgical specimens were significantly smaller (12.6 cm3, P .06). In nine patients for whom a surgical specimen was available, no modality adequately depicted superficial tumor extension; this was due to limitations [...]

9/28/2004 A Altieri, C Bosetti, et al OralOncol, October 1, 2004; 40(9): 904-9 We examined the relation between consumption of different types of alcoholic beverages and the risk of oral and pharyngeal cancer, using data from a case-control study conducted in Italy and Switzerland between 1992 and 1997. This included a total of 749 cases of oral and pharyngeal cancer and 1,772 hospital controls, admitted for acute, non-neoplastic conditions, unrelated to alcohol and smoking consumption. Significant trends in risk were found with increasing total alcohol intake, with multivariate odds ratios (OR) of 2.1 for drinkers of 3-4 drinks/day, as compared to abstainers or light drinkers (#10877;2 drinks/day), 5.0 for 5-7, 12.2 for 8-11 and 21.1 for #10878;12 drinks/day. Similar increased risks for subsequent levels of consumption were found for wine drinkers. After allowance for wine intake, the ORs for beer drinkers were 1.2 for 1-2 drinks/day, and 2.3 for #10878;3 drinks/day. Corresponding values for spirit drinkers were 1.0 and 1.9. Patterns of risk for wine drinkers were similar for wine only drinkers and drinkers of wine, plus beer and spirits. Our study indicates that in populations with frequent wine consumption, wine per se can strongly increase the risk of cancer of the oral cavity and pharynx, and confirms that the most prevalent alcoholic beverage in each population tends to be the one with the highest risk.

9/28/2004 Gail Topping & JA Critchley, B Unal. Evidence-Based Dentistry, 2004, Volume 5, Number 3, Pages 79-79 Data sources Medline, Embase, CINAHL and Dissertation Abstracts were searched, supplemented by screening reference lists, smoking-related websites, and contacting experts. Study selection Analytical observational studies of use of smokeless tobacco (ST; cohorts, case-control, cross-sectional studies) with a sample size of 500 were included if they reported on one or more of the following outcomes: mortality from any cause, oral and pharyngeal cancers, other cancers, cardiovascular diseases, dental diseases, pregnancy outcomes or surgical outcomes. Data extraction and synthesis Data extraction covered control of confounding, selection of cases and controls, sample size, clear definitions and measurements of the health outcome, and ST use. Selection, extraction and quality assessments were carried out by one or two independent reviewers. Results Many of the studies lacked sufficient power to estimate precise risks, mainly because of the small number of ST users. Studies were often not designed to investigate ST use, and many also had major methodological limitations including poor control for cigarette smoking and imprecise measurements of exposure. Studies in India showed a substantial risk of oral or oropharyngeal cancers associated with chewing betel quid and tobacco. Studies from other regions and of other cancer types were not consistent. Few studies have adequately considered the non-cancer health effects of ST use. Conclusions Chewing betel quid and tobacco is associated with a substantial risk of oral cancers in India. Most recent studies from the US and Scandinavia are not [...]

9/27/2004 TAMPA, FL Ivanhoe Broadcast News HealthCentral.com Combining radiation and chemotherapy to kill cancer cells is often very difficult on patients because of the side effects, but new research shows the results may be worth it. Days like this with her family make it all worthwhile for Ruth Toseland. Three years ago, she was diagnosed with tongue cancer. A portion of her tongue was removed, but the cancer came back. After two more surgeries, she opted for an extreme treatment -- radiation combined with chemotherapy. Oncologist Julie A. Kish, M.D., of Moffitt Cancer Center in Tampa, Fla., was involved in a national study that may change the treatment of choice for patients at high risk for recurrence. "At two years, the recurrence rate was lower in patients that had the combined treatment as opposed to radiation alone," she tells Ivanhoe. But the treatment is very hard on the patient. Researchers say four of the 228 patients in the study died as a result of the combined therapy. Still, Dr. Kish says, for some, the tough approach is worth it. "If you can prolong the time until the cancer comes back, which potentially, at some point in time, it may not come back, which we never say because we can't predict that, it's worth going through it." Ruth finished her treatment two and half years ago. So far, the cancer has not returned. Her husband, Michael, says, "We've got a lot to be thankful for. It was touch and go for [...]

9/27/2004 Ritesh Gupta, MD, MPH; Hitinder Gurm, MD; John R. Bartholomew, MD Archives of Internal Medicine, 2004;164:1845-1849 This article discusses the evolution of smokeless tobacco in the United States and interprets the available data on cardiovascular risk factors and cardiovascular mortality associated with its use. There has been a resurgence of smokeless tobacco use since 1970. Smokeless tobacco consistently produces levels of nicotine higher than those seen with smoking and causes similar sympathetic neural stimulation and acute cardiovascular effects. However, there is conflicting evidence from prospective and case-control studies about cardiovascular mortality or myocardial infarction caused by smokeless tobacco use. Smokeless tobacco use is also associated with oral cancers and high-risk behavior in adolescents. Although the evidence is not conclusive, the adverse cardiovascular effects of smokeless tobacco use are less than those caused by smoking but are more than those found in nonusers. It is advisable to counsel all current users of smokeless tobacco to quit. Behavioral counseling, sustained-release bupropion hydrochloride therapy, and nicotine replacement therapy may be safe therapeutic modalities for treatment of smokeless tobacco use. From the Departments of Internal Medicine (Dr Gupta) and Cardiovascular Medicine (Drs Gurm and Bartholomew) and the Section of Vascular Medicine (Dr Bartholomew), The Cleveland Clinic Foundation, Cleveland, Ohio.

9/30/2004 Houston, TX Journal of Clinical Oncology A new study shows that a history of smoking affects survival in patients with cancer of the head and neck. Patients who had smoked fewer than 100 cigarettes in their lifetime were three times more likely to have better overall survival, disease-specific survival, and recurrence-free survival compared with patients who had a current or previous history of regular smoking. There are approximately 38,000 new cases of head and neck cancer cases in the U.S. each year, the vast majority of which occur in smokers. The study, to be published October 1 in the Journal of Clinical Oncology, is the first to compare survival in pairs of head and neck cancer patients who differ in smoking status but are matched for other factors. The study provides a more accurate assessment of the link between smoking status and survival by limiting other factors that could affect observed disease outcome. "These findings support previous studies indicating that molecular differences exist between the tumors of smokers and non-smokers and may actually reflect two separate types of head and neck cancer," said Erich M. Sturgis, MD, MPH, in the Department of Head and Neck Surgery at the University of Texas M. D. Anderson Cancer Center and senior author of the study. "Our study suggests that the changes that occur in smokers may lead to a more aggressive form of the disease that results in poorer survival." Although the relative risk of developing head and neck cancer is three [...]

9/30/2004 Volkert B. Wreesmann, Weiji Shi et al. Journal of Clinical Oncology, Vol 22, No 19, 2004: pp. 3965-3972 PURPOSE The goal of this study was to identify chromosomal aberrations associated with poor outcome in patients with head and neck squamous cell carcinoma (HNSCC). PATIENTS AND METHODS We assessed the global genomic composition of 82 HNSCCs from previously untreated patients with comparative genomic hybridization (CGH). The CGH data were subcategorized into individual cytogenetic bands. Only genomic aberrations occurring in more than 5% of cases were analyzed, and redundancies were eliminated. Each aberration was submitted to univariate analysis to assess its relationship with disease-specific survival (DSS). We used Monte Carlo simulations (MCS) to adjust P values for the log-rank approximate 2 statistics for each abnormality and further applied the Hochberg-Benjamini procedure to adjust the P values for multiple testing of the large number of abnormalities. We then submitted abnormalities whose univariate tests resulted in an adjusted P value of less than .15 together with significant demographic/clinical variables to stepwise Cox proportional hazards regression. We again verified and adjusted P values for the 2 approximation of the final model by MCS. RESULTS CGH analysis revealed a recurrent pattern of chromosomal aberrations typical for HNSCC. Univariate analysis revealed 38 abnormalities that were correlated with DSS. After controlling for multiple comparisons and confounding effects of stage, five chromosomal aberrations were significantly associated with outcome, including amplification at 11q13, gain of 12q24, and losses at 5q11, 6q14, and 21q11 (MCS adjusted P = .0009 to [...]

9/28/2004 University of Michigan BY PATRICIA ANSTETT Detroit Free Press Kenji Izumi enters a small sterile room at the University of Michigan Medical Center, scrubbed and covered head to toe in white plastic disposable garments. A research scientist, he's the caretaker for a collection of cells that will grow to millions in just two weeks. When he gets enough -- he needs a supply the size of a quarter -- the cells will be harvested as mouth grafts, for surgical treatment of oral cancers and periodontal disease. Eventually, the product could be used for other skull and facial problems. But oral surgeons found problems using such grafts in the mouth to repair wounds after surgery for oral and throat cancers and periodontal disease. Kenji Izumi, a visiting assistant research scientist at U-M, is the caretaker of a group of cells that will grow to millions in two weeks. Skin grafts are rigid, don't always last long and some -- heaven forbid -- grow hair like real skin does, says Dr. Stephen Feinberg, professor and associate chair of research at U-M's section of Oral & Maxillofacial Surgery, in the Department of Surgery. The grafts the U-M team are working on do not grow hairbecause the cells come from inside a person's mouth. Last month, Feinberg's U-M team began clinical studies with EVPOME, the oral mucosal tissue product for which the team has a pending patent application. The product is made from cells obtained from the oral mucosal tissue that covers most [...]