Patrick Maisonneuve

Mortality after the Treatment of Hyperthyroidism with Radioactive Iodine

BACKGROUND Hyperthyroidism affects many organ systems, but the effects are usually considered reversible. The long-term effects of hyperthyroidism on mortality are not known. METHODS We conducted a population-based study of mortality in a cohort of 7209 subjects with hyperthyroidism who were treated with radioactive iodine in Birmingham, United Kingdom, between 1950 and 1989. The vital status of the subjects was determined on March 1, 1996, and causes of death were ascertained for those who had died. The data on the causes of death were compared with data on age-specific mortality in England and Wales. The standardized mortality ratio was used as a measure of relative risk, and the effect of covariates on mortality was assessed by regression analysis. RESULTS During 105,028 person-years of follow-up, 3611 subjects died; the expected number of deaths was 3186 (standardized mortality ratio, 1.1; 95 percent confidence interval, 1.1 to 1.2; P<0.001). The risk was increased for deaths due to thyroid disease (106 excess deaths; standardized mortality ratio, 24.8; 95 percent confidence interval, 20.4 to 29.9), cardiovascular disease (240 excess deaths; standardized mortality ratio, 1.2; 95 percent confidence interval, 1.2 to 1.3), and cerebrovascular disease (159 excess deaths; standardized mortality ratio, 1.4; 95 percent confidence interval, 1.2 to 1.5), as well as fracture of the femur (26 excess deaths; standardized mortality ratio, 2.9; 95 percent confidence interval, 2.0 to 3.9). The excess mortality was most evident in the first year after radioiodine therapy and declined thereafter. CONCLUSIONS Among patients with hyperthyroidism treated with radioiodine, mortality from all causes and mortality due to cardiovascular and cerebrovascular disease and fracture are increased.

European School of Oncology Advisory report to the European Commission for the “Europe Against Cancer Programme” European Code Against Cancer

A European School of Oncology Advisory Group has reviewed the European Code Against Cancer after its initial use over a 6-year period. With minor modifications, the original ten recommendations were found to be adequate, although it was agreed that an Annex was necessary to explain the scientific evidence supporting each point, and is presented herewith. Tobacco smoking clearly remains the most important cause of cancer, and now it can be quantified better than ever before. It is also clear that it is never too late to stop smoking: stopping even in middle age, prior to the onset of serious illness has a beneficial effect on life expectancy. Alcohol drinking is an important cause of cancer, and yet modest consumption levels protect against cardiovascular disease mortality. The optimal strategy seems to be a consumption not exceeding 2-3 drinks per day, although this limit may be lower for women. Increased consumption of fruits and vegetables, reduction in consumption of fatty foods, reduction of obesity and increased physical activity can all be recommended to reduce cancer risk. Exposure to excessive sunlight remains a problem which should be limited. Control of occupational cancer is a three-way partnership: legislation identifies and limits exposure to known carcinogens, employers enact the legislation and workers should respect the measures introduced. There are a number of signs and symptoms which may lead to cancer being diagnosed earlier, and patients with these should be referred to a doctor. For women, participation in organised programmes of cervical cancer and breast cancer (after 50 years of age) should lead to a reduction in mortality from these forms of cancer. The key element is organised programmes, where quality control and quality assurance are in force. These revised recommendations are the result of an agreement following advice, review and dialogue with cancer experts throughout Europe. They were approved by the European Community Cancer Experts at their meeting in Bonn on 28-29 November 1994. Their implementation by the European population should greatly reduce cancer incidence and mortality.

Genetic polymorphism of N-acetyltransferases, glutathione S-transferase M1 and NAD(P)H:quinone oxidoreductase in relation to malignant and benign pancreatic disease risk

Carcinogens present in cigarette smoke and diet have been associated with pancreatic cancer. We hypothesized that heterocyclic and aromatic amines implicated in these exposures could be involved as causative agents and that therefore genetic variation in enzymes metabolizing these carcinogens could modify the risk of developing malignant and benign pancreatic disease. The effect of the genetic polymorphism of acetyltransferases (NAT1 and NAT2), glutathione S-transferase Ml (GSTM1) and NAD(P)H: quinone oxidoreductase 1 (NQO1) on the risk of pancreatic diseases (cancer, pancreatitis) was examined in a case—control study. PCR-based assays were used for genotype analysis of genomic DNA from whole blood cells. Samples collected from Caucasian patients with diagnosed pancreatic cancer (n=81), with non-alcoholic (n = 41) and alcoholic pancreatitis (n= 73) and from asymptomatic control subjects (n=78) were analysed. The prevalence of GSTM1 null genotype and of NAT2 fast and slow acetylator genotypes and the distribution of frequencies for NQO1 genotypes did not differ in subjects with pancreatic diseases vs controls. For NAT1 slow acetylators a non-significant excess (P=0.18) was found among pancreatic cancer cases vs controls. There was a significant over-representation of the GSTM1 AB or B genotype in all pancreatic disease cases combined (OR=2.6; P<0.05). When concurrent controls were pooled with literature controls (n=1427), OR was 1.4 (P= 0.08). The results of this study, requiring confirmation, suggest that the polymorphism of GSTM1 and NAT1 enzymes may be associated with a modest increase in susceptibility to pancreatic disease

Analysis of quantitative data by quantiles in epidemiologic studies: classification according to cases, noncases, or all subjects?

Quantitative exposure data in epidemiologic studies are frequently analyzed by ordered categories. Categorization by quantiles can be based on the distribution of (1) cases, (2) noncases, and (3) all subjects. The advantages of the three schemes in determining quantiles were compared. They were found to give the same power regarding a test for trend over a wide range of study situations. Considerations on the representativeness and the ease of the analysis implementation could dictate the choice of the categorization scheme.

Cancer control in women. Update 2003

The global cancer burden in women appeared to be increasing quickly at the end of the twentieth century with notable increases in the absolute numbers of cases of breast, cervix, lung and colorectal cancer of concern. However, prospects for cancer control in women appear to be good within our current knowledge and deserve close attention. Rates of lung cancer in women are increasing substantially in many countries and seem set to overtake breast cancer as the commonest form of cancer death in women in many parts of the world. These changes are due to the effects of cigarette smoking, a habit which women widely embraced during the second half of the last century. The high levels of smoking current in young women, which have yet to have their full impact on death rates, constitute an important hazard not only for future cancer risks but for several other important causes of death.

Epidemiology of benign prostatic hyperplasia: present knowledge and studies needed.

Despite being such a common condition, morphologically prevalent in 88% of autopsies of old (greater than 80 years) men, little epidemiologic research has been undertaken on benign prostatic hyperplasia (BPH). The prevalence of BPH, and probably the incidence, increases with age although the belief that BPH is a direct consequence of aging per se still awaits proof. Many observers have concluded that the age association reflects age-related hormonal changes, although this also requires proof. BPH is a very common condition in aging men: 3 in every 10 may ultimately require surgery for this condition if current estimates of prevalence are correct. Despite its common occurrence, little is known with any degree of certainty about risk factors for BPH apart from being male, being old, and having had a pair of functioning testicles since puberty. There are good reasons why the epidemiology of BPH has remained poorly understood although the application of more epidemiologic thought could pay great dividends, particularly if prostate screening programs could be exploited maximally.

Incidence of prostate cancer will double by the year 2030: the argument for.

Prostate cancer is a frequent cancer in old men which increases with age and is associated with wide geographical variation. Even if age-specific incidence rates remain stable, the problem of prostate cancer seems certain to increase in absolute terms simply because of the ageing of the population. This will have major economic implications for the future, particularly in Westernised societies, with any temporal trend in risk serving only to further compound the problem. However, since the risk of dying from prostate cancer has remained unchanged in many countries throughout this century, it may be that the increased incidence may be the result of increasing transurethral resection of the prostate procedures or screening techniques which have increased the detection and reporting of prostate cancer.

Case mix at the European Institute of Oncology: First report of the Tumour Registry, years 2000-2002

Introduction: An institutional and centralized hospital-based tumour registry (TR) is the ideal supporting tool for the organization and management of clinical data in a comprehensive cancer centre. The purpose of this paper is to describe the development of the TR at the European Institute of Oncology (IEO), Milan, Italy, from its origin to its current applications. Material and methods: After a series of meetings with members of administrative, clinical, research and informatics departments, the TR was activated in March 2006 with the aim of collecting data on all the individuals referred to the institute, with or at risk of developing a tumour. It was implemented on an Oracle™-based interface. A minimum dataset of variables was defined and data collection was divided into four forms, which together gather all the relevant data on patients, tumours, treatments and subsequent events. Results: After a six-month pilot period, which involved the training of the tumour registrars, adjustments to the structure of the registry, development of a data quality control procedure and finalization of the operative protocol, since September 2006 the data collection has been fully operative. Five registrars have been chronologically entering data of all individuals who visited the IEO for the first time since 1 January 2000. As of March 2009, data on 69,637 individuals and 43,567 tumours has been reviewed, recoded and registered in the TR. Twenty-two per cent of the tumours (n=9578) were first invasive primaries, diagnosed and treated in the IEO; the most common sites were breast (n=4972), lung (n=627), intestines (n=479) and prostate (n=376). Conclusion: The IEO TR has been proven functional and reliable in monitoring the activity of the hospital, allowing extraction of data from any subpopulation with characteristics of interest. The structured and centralized TR represents an important tool for our research-oriented institution.