Tumor incidence in related hematopoietic stem cell donors.

Late malignancies have been discussed as a potential risk for growth factor mobilized donors of hematopoietic stem cells. Little is known about the incidence and potential risk factors. This single center retrospective cohort study evaluated all HLA-identical sibling pairs with hematopoietic stem cell transplantation (HSCT) for a hematological malignancy, treated from 1974 to 2001 at the University Hospital of Basel. Three hundred eighteen pairs were identified, 291 donors (92%) could be contacted. Median observation time was 13.8 years (range 5-32 years). Sixteen (5%) donors had developed a total of 18 tumors, 17 recipients a secondary tumor. According to the age- and sex-adapted cancer incidence, 3.3 tumors in male and 6.8 in female donors were expected, 3 (relative risk (RR): 0.91, 95% confidence interval: 0.19-2.66) and 4 (RR: 0.58, 95% confidence interval: 0.16-1.48), respectively, were found in donors between 0 and 49 years. Between 50 and 69 years, 4.5 tumors in males and 4.8 in females were expected, 5 (RR: 1.11, 95% confidence interval: 0.36-2.59) and 6 (RR: 1.23, 95% confidence interval: 0.45-2.67), respectively, were observed. Tumors do occur in donors of hematopoietic stem cells at least at the rate as expected in a normal population; whether incidence exceeds expected rates needs to be determined in larger international cohorts.

Variation in survival after diagnosis of breast cancer in Switzerland.

BACKGROUND: Survival after diagnosis of cancer is a key criterion for cancer control. Major survival differences between time periods and countries have been reported by the EUROCARE studies. We investigated whether similar differences by period and region existed in Switzerland. METHODS: Survival of 11,376 cases of primary invasive female breast cancer diagnosed between 1988 and 1997 and registered in seven Swiss cancer registries covering a population of 3.5 million was analysed. RESULTS: Comparing the two periods 1988-1992 and 1993-1997, age-standardized 5 year relative survival improved globally from 77% to 81%. Furthermore, multivariate analysis adjusting for age, tumour size and nodal involvement identified regional survival differences. Survival was lowest in the rural parts of German-speaking eastern Switzerland and highest in urbanised regions of the Latin- and German-speaking northwestern parts of the country. CONCLUSIONS: This study confirms that survival differences are present even in a small and affluent, but culturally diverse, country like Switzerland, raising the issue of heterogeneity in access to care and quality of treatment.

[Factors considered to choose type of a hysterectomy for benign uterus lesions (excluding prolapsus and obstetrical indications)]. / Facteurs du choix de la voie d'abord des hystérectomies pour lésions utérines bénignes (prolapsus et indications obstétricales exclus).

OBJECTIVES: We searched for the factors determining the type of hysterectomy (vaginal, laparoscopy or laparotomy) performed in women with supposedly benign uterine disease. MATERIAL AND METHOD: We conducted a retrospective study of 101 consecutive hysterectomies performed on voluminous uteruses, prolapsus and obstetrical indications excluded. The following factors likely to have influenced the decisions were examined: patient age, nulliparity, menopausal status, history of laparotomy, uterus weight, narrow vagina, nature of uterus lesions, associated unilateral or bilateral annexectomy, complications. RESULTS: The frequencies were: vaginal route 58.4% (average uterine weight 249.4 g, range 93-1149 g), laparoscopic preparation 37.6% (average uterine weight 348 g, range 92-818 g), and laparotomy 4% (average uterine weight 586.2 g, range 112-1216 g). Factors determining type of hysterectomy were uterine weight (and therefore volume) (p < 0.05), nulliparity (p < 0.04), narrow vagina probed by compulsory Schuchardt incision (p < 0.02), associated annexectomy (p < 0.01). No other factors were significantly determinant. The vaginal route appears to be highly preferred. CONCLUSION: Vaginal hysterectomy is clearly the most preferred and practiced. Laparoscopy may be helpful for vaginal hysterectomy and laparotomy is exceptional.

The impact of coding process on observed cancer mortality trends in Switzerland.

Official cancer mortality in Switzerland decreased by about 16% over the 9-year period 1990-1998 and this trend has often been used to suggest that secondary prevention by screening for breast cancer could be useless. However, the clear downshift observed between 1994 and 1995 for some cancers, such as female breast and prostate, and the simultaneous change in ICD classification used by the Federal Office for Statistics in 1995 (ICD-8 to ICD-10) could be related, suggesting an impact of coding process on the observed trend. For every death occurred between 1980 and 1999, the death certificates have been retrieved, the cause of death has been recoded and site-specific mortality rates have been calculated again for each year during this period. As suggested, the trend appears to be overestimated: in order to be comparable with current rates, the mortality observed before 1995 should be lowered by about 7% for men and 5% for women. The error may be partially due to attributing the cause of death to co-morbidity factors not normally (and nowadays) defined as the underlying cause. Logically, the impact of such a miscoding is more important among older people and for cancer sites with long survival. For instance, the correction should be around 15% for female breast, 12% for prostate and up to 40% for testicular cancer.

European health systems and cancer care.

INTRODUCTION: Data on the survival of all incident cases collected by population-based cancer registries make it possible to evaluate the overall performance of diagnostic and therapeutic actions on cancer in those populations. EUROCARE-3 is the third round of the EUROCARE project, the largest cancer registry population based collaborative study on survival in European cancer patients. The EUROCARE-3 study analysed the survival of cancer patients diagnosed from 1990 to 1994 and followed-up to 1999. Sixty-seven cancer registries of 22 European countries characterised by differing health systems participated in the study. This paper includes essays providing brief overviews of the state and evolution of the health systems of the considered countries and comments on the relation between cancer survival in Europe and some European macro-economic and health system indicators, in the 1990s. OVERVIEW OF THE EUROPEAN HEALTH SYSTEMS: The European health systems underwent a great deal of reorganisation in the last decade; a general tendency being to facilitate expanding involvement of the private sector in health care, a process which occurred mainly in the eastern countries (i.e. the Czech Republic, Estonia, Poland, Slovakia and Slovenia). In contrast, organisational changes in the northern European countries (i.e. Denmark, Iceland, Finland and Sweden) tended to confirm the established public sector systems. Other countries, including the UK and some southern European countries (i.e. England, Scotland, Wales, Malta and Italy) have reduced the public role while the systems remain basically public, at least at present. Our findings clearly suggest that cancer survival (all cancer combined) is related to macro-economic variables such as the gross domestic product (GDP), the total national (public and private) expenditure on health (TNEH) and the total public expenditure on health (TPEH). We found, however, that survival is related to wealth (GDP), but only up to a certain level, after which survival continues to be related to the level of health investment (both TNEH and TPEH). According to the Organisation for Economic Co-operation and Development (OECD), the TNEH increased during the 1990s in all EUROCARE-3 countries, while the ratio of TPEH to TNEH reduced in all countries except Portugal. CONCLUSIONS: Cancer survival depends on the widespread application of effective diagnosis and treatment modalities, but our enquiry suggests that the availability of these depends on macro-economic determinants, including health and public health investment. Analysis of the relationship between health system organisation and cancer outcome is complicated and requires more information than is at present available. To describe cancer and cancer management in Europe, the European Cancer Health Indicator Project (EUROCHIP) has proposed a list of indicators that have to be adopted to evaluate the effects on outcome of proposed health system modifications.

Cancer prevalence in Central Europe: the EUROPREVAL Study.

BACKGROUND: Information on cancer prevalence is either absent or largely unavailable for central European countries. MATERIALS AND METHODS: Austria, Germany, The Netherlands, Poland, Slovakia, Slovenia and Switzerland cover a population of 13 million inhabitants. Cancer registries in these countries supplied incidence and survival data for 465 000 cases of cancer. The prevalence of stomach, colon, rectum, lung, breast, cervix uteri, corpus uteri and prostate cancer, as well as skin melanoma, Hodgkin's disease, leukaemia and all malignant neoplasms combined was estimated for the end of 1992. RESULTS: A large heterogeneity was observed within central European countries. For all cancers combined, estimates ranged from 730 per 100 000 in Poland (men) to 3350 per 100 000 in Germany (women). Overall cancer prevalence was the highest in Germany and Switzerland, and the lowest in Poland and Slovenia. In Slovakia, prevalence was higher than average for men and lower than average for women. This was observed for almost all ages. As shown by incidence data, breast cancer was the most frequent malignancy among women in all countries. Among men, prostate cancer was the leading malignancy in Germany, Austria and Switzerland, and lung cancer was the major cancer in Slovenia, Slovakia and Poland. The Netherlands had a high prevalence of both prostate and lung cancer. Time-related magnitude of prevalence within each country and the variability of such proportions across the countries has been estimated and cancer prevalence is given by time since diagnosis (1 year, 1-5 years, 5-10 years, >10 years) for each site. The weight of 1-year prevalence (248 per 100 000 among men and 253 per 100 000 among women) was <15% of total prevalence. Prevalent cases between 1 and 5 years since diagnosis represented between 22% and 34% of the total prevalence. Prevalent cases diagnosed from 5 to 10 years before (335 per 100 000 for men and 505 per 100 000 for women) represented between 17% and 23% of prevalent cancers. Finally, long-term cancer prevalence (diagnosed >10 years before), reflecting long-term survival, and number of people considered as cured from cancer were 490 per 100 000 for men and 1028 per 100 000 for women, with a range between 26% (The Netherlands, men) and 50% (Slovakia, women). CONCLUSION: It is clear from observing countries in Central Europe, that high cancer prevalence is associated with well-developed economies. This burden of cancer could be interpreted as a paradoxical effect of better treatments and thereby survival. It could also be taken as a sign for not being satisfied with the advances in treating patients diagnosed with cancer, and for supporting more primary prevention.

Occupational risk factors, ultraviolet radiation, and ocular melanoma: a case-control study in France.

BACKGROUND: Ultraviolet radiation has been suspected as a possible cause of ocular melanoma. Because this association is controversial, we examine the role of occupational exposure to ultraviolet radiation on the occurrence of this rare cancer. MATERIAL AND METHODS: A population-based case-control study was conducted in 10 French administrative areas (départements). Cases were 50 patients with uveal melanoma diagnosed in 1995-1996. Controls were selected at random from electoral rolls, after stratification for age, gender, and area. Among 630 selected persons, 479 (76%) were interviewed. Data on personal characteristics, occupational history, and detailed information on each job held were obtained from face-to-face interviews using a standardized questionnaire. Estimates of occupational exposure to solar and artificial ultraviolet light were made using a job exposure matrix. RESULTS: Results show elevated risks of ocular melanoma for people with light eye color, light skin color, and for subjects with several eye burns. The analysis based on the job exposure matrix showed a significantly increased risk of ocular melanoma in occupational groups exposed to artificial ultraviolet radiation, but not in outdoor occupational groups exposed to sunlight. An elevated risk of ocular melanoma was seen among welders (odds ratio = 7.3; 95% confidence interval = 2.6-20.1 for men), and a dose-response relationship with job duration was observed. The study also showed increased risk of ocular melanoma among male cooks, and among female metal workers and material handling operators. CONCLUSION: Following the present study, the existence of an excess risk of ocular melanoma in welders may now be considered as established. Exposure to ultraviolet light is a likely causal agent, but a possible role of other exposures in the welding processes should not be overlooked.

Surveys on mammography frequency in Geneva.

Two surveys were conducted in Geneva, in 1991 and 1995, to assess the coverage of mammography before the introduction of a breast cancer screening programme. Women who attended for mammographies did so at their own request, or were referred by doctors (more by gynaecologists than general practitioners). In 1995, the total female population was around 200,000, of which the target population for screening (age group 50 to 69) was 46,000 persons. The total number of mammographies observed increased by 23%, with a higher increase for "routine" mammographies (+35%). However, these figures hide certain trends, with a high proportion of educated women performing regular breast investigations. The two year coverage rate for mammography among the 50 to 69 age group is estimated at 38%, which means that about 20,000 women within this target population in Geneva still escape screening.

Completeness of cancer registration: a new method for routine use.

We report a new method of estimating the completeness of cancer registration, in which the proportions of unregistered patients are derived from the time distributions of three probabilities, each of which can be directly estimated from the registry's own data--the probabilities of survival, of registration of the cancer during the patient's life, and of the mention of cancer on the death certificate of a cancer patient who dies. This method allows completeness to be assessed routinely by factors such as age, sex, geographical area and tumour type.

[Is systematic clinical breast examination in women still indicated?]. / L'examen clinique systématique des seins féminins, est-il toujours d'actualité?

Screening for breast cancer is not generalized in France. In order to evaluate any change in clinical practice, we reviewed three cohorts of one hundred successive breast cancers diagnosed in a geographical area without a breast screening campaign, starting in 1978, 1999 and 1996. The proportion of T1 (UICC) shifted from 32% to 50% and the rate of positive nodes among these T1 patients from 63% to 26% from the 1978 cohort to the 1996 cohort. There was an unchanged proportion (20%) of T4 patients in all three cohorts. Conservative treatment improved from 32% to 78% (p > 0.001). Systematic clinical breast examination should be strongly encouraged to lower the high proportion of T4 patients.

Combination but not single-agent methotrexate chemotherapy for gestational trophoblastic tumors increases the incidence of second tumors.

PURPOSE: No increase in second tumor incidence was found in a previous analysis of women treated with chemotherapy for gestational trophoblastic tumors (GTT). More patient years at risk enabled a further analysis of the risk of second tumors to be performed in the 1,377 women treated in this until up to 1990. PATIENTS AND METHODS: Health questionnaires were returned on 93.3% of patients who successfully completed chemotherapy and were living in the United Kingdom. The remainder were flagged for death or developing further cancers by the Office of Population Census and Surveys and by the Thames Cancer Registry. Incidence density analysis was performed based on 15,279 person-years of observation available. Standardized incidence ratio (SIR) was used to estimate the relative risk (RR) of second tumors associated with the treatment. To calculate the expected number, the actual incidence rates observed by the Thames Cancer Registry during the same calendar period of observation were used. RESULTS: An overall 50% excess of risk (RR = 1.5; 95% confidence interval [CI], 1.1 to 2.1; P < .011) was observed: there were 37 second tumors, when 24.5 were expected. For specific second tumors, the risk was significantly increased for myeloid leukemia (RR = 16.6; 95% CI, 5.4 to 38.9), colon (RR = 4.6; 95% CI, 1.5 to 10.7), and breast cancer when the survival exceeded 25 years (RR = 5.8; 95% CI, 1.2 to 16.9). The risk was not significantly increased among the 554 women receiving single-agent therapy (RR = 1.3; 95% CI, 0.6 to 2.1). Leukemias only developed in patients receiving etoposide plus other cytotoxic drugs. CONCLUSION: This study suggests that there is a slight increased risk of second tumors after sequential or combination chemotherapy for GTT. This has become apparent since the introduction of etoposide and longer follow-up.

[Cancer trends and health care planning: toward a better use of cancer registries]. / Tendances évolutives du cancer et prévision des besoins: vers une meilleure utilisation des registres du cancer.

Cancer registries are instruments for cancer surveillance in the whole population. They provide information not only on the current burden of cancer, but--by projection from current occurrence rates and recent trends--on the likely future burden. Cancer risk is increasing in many developed countries, and increasing life expectancy in the next 10-30 years will have a disproportionate effect on the number of cancer patients at advanced ages. Cancer registries are the only type of organisation capable of providing information on cancer in the population as a whole, and of estimating recent trends and future risks of cancer on a national scale. At present, however, cancer registries in France appear not to be used to their full potential for the development of public health strategy. This may be because they have inadequate resources to produce the desired information, or perhaps simply because there is ignorance of their activity and potential. In order to improve the utility of cancer registries, it would be possible to use the British model of establishing service level agreements with the funding authorities. The objectives of such agreements include measures of the quality of data collected, and the extent to which useful information is derived. Simple measures of the volume of research published, while useful, are inadequate as the sole index of activity or criterion for funding. A fresh national strategy is required in France, in order to create a network of efficient cancer registries with stable funding. The long-term benefits in cancer control would be immense.

Deprivation, stage at diagnosis and cancer survival.

The association between an area-based measure of deprivation and survival from the 10 most common cancers was studied in 155,682 patients diagnosed between 1980 and 1989 in the area covered by the South Thames Regional Health Authority. Furthermore, the impact of stage of disease at diagnosis on this association was studied. The measure of deprivation was the Carstairs Index of the census enumeration district of each patient's residence at diagnosis (5 categories) and the cancers studied were: lung, breast, colorectum, bladder, prostate, stomach, pancreas, ovary, uterus and cervix. In the univariate analyses the measure of outcome was the relative survival rate and in the multivariate analyses it was the hazard ratio. Both univariate and multivariate analyses showed that patients from affluent areas had better survival than patients from deprived areas for cancers of the lung, breast, colorectum, bladder, prostate, uterus and cervix. Stage of disease at diagnosis did not explain the survival differences by deprivation category. For cancers of the stomach, pancreas and ovary, no variation in survival by deprivation category was found. For most cancer sites, a clear gradient in survival by deprivation category was observed, which implies a large potential reduction of cancer mortality among the lower socioeconomic groups. Future studies need to incorporate other possible explanatory factors, besides stage, of the association between deprivation and survival.

Deprivation and survival from breast cancer.

We studied the association between deprivation and survival from breast cancer in 29,676 women aged 30 and over who were diagnosed during the period 1980-89 in the area covered by the South Thames Regional Health Authority. The measure of deprivation was the Carstairs Index of the census enumeration district of each woman's residence at diagnosis. We studied the impact of stage at diagnosis, morphology and type of treatment on this association, with the relative survival rate and the hazard ratio as measures of outcome. There was a clear gradient in survival, with better survival for women from more affluent areas. At all ages, women in the most deprived category had a 35% greater hazard of death than women from the most affluent areas after adjustment for stage at diagnosis, morphological type and type of treatment. In younger women (30-64 years), the survival gradient by deprivation category cannot be explained by these prognostic factors. In older women (65-99 years), part of the unadjusted gradient in survival can be explained by differences in the stage of disease: older women in the most deprived category were more often diagnosed with advanced disease. Other factors, so far unidentified, are responsible for the gradient in breast cancer survival by deprivation category. The potential effect on breast cancer mortality of eliminating the gradient in survival by deprivation category is substantial (7.4%). In women aged 30-64 years, 10% of all deaths within 5 years might be avoidable, while in older women this figure is 5.8%.

Trends in primary cerebral lymphoma.

Primary non-Hodgkin lymphoma of the brain is rare, representing only 1% of all non-Hodgkin lymphomas (NHLs), but its incidence has been increasing rapidly in south-east England since 1985. Among 17,322 cases of NHL registered during the 18 year period 1973-90, there were 210 cases of primary cerebral NHL, of which 179 (86%) were diagnosed in the last third of this period, 1985-90. This increase in cerebral lymphoma is not adequately explained by improvements in the precision of diagnosis or by changes in disease coding or cancer registration practice. While there has also been a rapid increase in Kaposi sarcoma, neither immunosuppression acquired through HIV infection nor the overall trend in non-Hodgkin lymphoma can satisfactorily explain the recent increase in cerebral lymphoma, which affects all ages and both sexes similarly. Other possible causes for a true increase in cerebral lymphoma should be sought.

Comparison of anti-HBe-positive and HBe-antigen-positive chronic hepatitis B in France. French Multicentre Group.

Two groups of patients with HBV DNA-positive chronic active hepatitis B, from 20 French hospitals, separated according to HBe status, were prospectively subjected to a comparative analysis of various epidemiological, clinical, biochemical, serologic and histologic features. There were 61 patients with anti-HBe and 215 patients with HBeAg. At diagnosis, 25 variables were compared between the two groups. Some of the patients were followed up for 1 year. Anti-HBe chronic hepatitis B occurred with a prevalence of 22.1%. In the anti-HBe-chronic hepatitis B group, the patients were older, and more often of Southern European origin; the source of infection was more frequently unknown, hepatitis B markers were more frequently observed within the family, and the estimated duration of liver disease was longer. Serum HBV DNA levels were lower in the anti-HBe-positive group. No difference was observed in ALT levels at diagnosis and during follow up in the patients studied. Cirrhosis was more frequent in the anti-HBe-positive group. There was no difference in histological activity score between the two groups. These results suggest that anti-HBe-positive, chronic active hepatitis B is not rare in France, and that the higher occurrence of cirrhosis in this group may be related to a longer duration of the disease.