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.

[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.

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.

[Hepatic metastasis of unknown primary site]. / Métastases hépatiques de site primitif inconnu.

In this retrospective study, 91 patients (30%) out of a series of 304 with metastatic cancer of unknown primary site were found to have liver metastases. The liver was the only metastatic site in 28 (31%) cases and was associated with other sites in 63 (69%) cases. Median age was 62 yr in 61 male patients and 59 yr in 30 female patients. Thirty patients were submitted to an extensive investigation in search of the primary tumor, including systematic endoscopies: no primary cancer was found in these patients. In 61 other patients, only symptom-oriented investigations were performed and the primary cancer was found in 11 cases. The histologic type was adenocarcinoma in 71 (78%) cases, undifferentiated in 11 (12%) cases, epidermoid in 5 (6%) cases and determined by cytology alone in 4 cases. The median survival was 4 months in patients with metastases in the liver only, and 5 months in the other patients. This difference was not significant, so prognostic factors such as the Karnofsky index, weight loss, CEA and LDH levels were evaluated in the entire group; these factors do not have significant prognostic value. By contrast, when patients were able to receive chemotherapy, median survival was better (4 months) than without (median survival: 1 month; P = 0.005). In addition, in the case of objective response to chemotherapy, the median survival was 9 months versus 3.5 months for patients without objective response (P = 0.001). Seventy-three out of 91 patients (80%) were treated with chemotherapy regimen; 65 patients were evaluable: the objective response rate was 11 +/- 7% (7/65). Different regimens were used. With a non-toxic combination of fluorouracil, vinblastine and cyclophosphamide, 3 partial responses greater than or equal to 50% out of 43 patients (7 +/- 8%) were obtained. No significant advantage was observed when adriamycin was added to FU (4/13): 31 +/- 25%. Second- or third line chemotherapy regimen due to progression of the disease after the first-line combination provided only one objective response out of 36 patients. According to this retrospective study we recommend that overinvestigation be avoided in patients, with liver metastases of unknown primary site and that these patients be treated with non-toxic drug combinations.

[Is the intestinal lavage with a solution of mannitol effective in the prevention of post-hemorrhagic hepatic encephalopathy in patients with liver cirrhosis? Results of a randomized prospective study]. / Le lavage intestinal par une solution au mannitol est-il efficace dans la prévention de l'encéphalopathie hépatique post-hémorragique chez le malade atteint de cirrhose?

OBJECTIVES: The aim of this study was to evaluate the usefulness of whole gut irrigation with a mannitol solution in the prevention of hepatic encephalopathy in patients with cirrhosis and bleeding oesophageal or gastric varices. METHODS: The randomized prospective study included 40 patients with a mean age of 59.6 +/- 9.6 years. Bleeding was controlled by a Blakemore or Linton haemostatic tube, in all cases. The patients were divided into a "mannitol" group (n = 20) treated by whole gut irrigation with a 5 L solution containing 40 g/L of mannitol, and a "control" group (n = 20). The two groups did not differ for age, sex, aetiology of cirrhosis or gastrointestinal bleeding, Child-Pugh classification, delay of minimum fare or the number of transfused blood units. The onset of hepatic encephalopathy was investigated within the first 48 hours after the beginning of gastrointestinal bleeding. The grade of hepatic encephalopathy was established using an index with 4 criteria (mental status, asterixis, number connection test, arterial ammonia concentrations), each with 5 grades of severity. RESULTS: There were no adverse side-effects in the mannitol group. The incidence of hepatic encephalopathy (5 vs 30%) and the length of hospitalization (8.2 +/- 2.3 vs 13.6 +/- 3.1 days) were significantly decreased in the mannitol group (P < 0.05). Mortality was not different between the 2 groups (P = 0.4). CONCLUSION: Whole gut mannitol irrigation appears to be an effective, simple, inexpensive, well tolerated technique in the prevention of hepatic encephalopathy after variceal bleeding in patients with cirrhosis.

[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.

[Critical analysis of a clustering method applied to the study of geographic distribution of cancer]. / Analyse critique d'une méthode de regroupement appliquée à l'étude de la répartition géographique du cancer.

Cancer registration permits to elaborate atlases that describe the spatial distribution of incidence within the registration area. The division of this area in small units is usually an administrative one, leading a wide range of unit sizes. Hence, results of indirect standardization are often difficult to interpret, due to the large variability of the observed cases. We used Huel's method (1986), which is based on the grouping of contiguous geographical zones that have the same incidence level. Here are displayed the results for cancer incidence within the "département de l'Isère" (France). We focus on method mechanisms and on the impact of the choice of the risk level.

[Incidence of colonic and rectal tumors as a function of the urban and rural characteristics of the residential area in the Isère district (1979-1985), France]. / Incidence des tumeurs coliques et rectales en fonction du caractère urbain et rural de la zone de résidence, dans le département de l'Isère (1979-1985), France.

From 1979 to 1985, 1443 new malignant tumors of the colon and 1017 of the rectum appear in the departement of Isère (France). Using the urban category of "Zone de Peuplement Industriel et Urbain" (Z.P.I.U), we were able to classify place of residence within 3 strata, according to the proportion of inhabitants of the rural (or urban) type. For both sexes, incidence of colon carcinomas is higher in urban categories than in rural ones. For males, incidence of rectal carcinomas is higher within areas of the rural type. Going from the urban category of the rural one, "urban" being the level of reference. Relative Risks for men are 1,0.9 and 0.6 for the colon, and 1, 1.3 and 1.2 for the rectum. For women, RR's are 1,0.8, and 0.7 for colon, and 1,1.0, and 0.8 for the rectum. Same results are described in the literature, with higher risks for colon cancers in urban areas. Our results reporting lower incidence for rectal carcinomas in Isère among men, are in contradiction with other results in the literature. This work supports the idea that epidemiology of large bowel carcinomas should focus onto segments. Second, when categories of residence allow it, it is worthwhile looking at gradients that bring more information on the relation, than the simple dichotomy: urban versus rural.

[Incidents of brain tumors observed in the Grenoble area (canton of Meylan) 1979-1990]. / Etude des cas incidents de tumeurs intra-crâniennes observés entre 1979 et 1990 dans la région de Grenoble (canton de Meylan).

A high excess of risk (standardized incidence ratio S.I.R.: 320 [190-490]) of intracranial tumors among men living within the county of Meylan, in the suburb area of Grenoble, as compared with the overall population was shown by the Isère Cancer Registry, for the period 1979-1984. There has been no change of this excess of risk between 1979 and 1990 (S.I.R. = 190). The pathological homogeneity of this cluster (neuroglial tumors) among men is noticeable. This county is known as a concentration of high-tech and intellectual professional activities. A descriptive study was conducted on the 24 cases diagnosed between 1979 and 1990, based on retrospective interviews of patient's family. Ethnical origins, blood groups, personal and familial medical history (with special interest in cranial injuries), socio economic status, chemicals, radiations and electro-magnetic exposures, acoustic and visual exposures (such as noises and T.V.), drinking water, tobacco and food consumptions, were investigated. Educational level, occupation, and European ethnic origin are all pointing to the same direction: a higher risk in high level social classes and high level professions. An analytical study is going on, that would give a deeper insight in these phenomenons.

[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.

[Clinical data and descriptive epidemiology of primary bronchial cancer. 9 years of activity of the Isère Registry]. / Données cliniques et épidémiologie descriptive du cancer bronchique primitif. Neuf années d'activité du Registre de l'Isère.

Systematical registration of morbidity for lung carcinoma of the primary type was performed since January 1979 for the department of Isere, where a population of 940,000 inhabitants are living. Results for nine years registration (1979-1987) are dealing with 2,590 new cases. Crude incidence for primary lung carcinoma is 55.7 per 100,000 among men, and 5.9 for women (sex ratio: 11.7). Upper lobe is the site more concerned. There is no preference as regard laterality. When lymphatic nodes are explored (32%), there is an extension of the carcinoma for 75.2% of them. At the moment of the diagnostic, there is already a metastasis for 24% of the patients, mainly for bones. Among men and women, proportions for the squamous cell type are respectively 52.6% and 22.3% (60.8% and 28.7% of histologically identified cases), for the small cell type: 18.4% and 16.3% (21.2% and 21.0% of histologically identified cases), and for glandular carcinomas: 13.2% and 32.1% (11.9% and 41.5% of histologically identified cases). Results of the pathological examination are known in 92.8% for primary lung carcinoma cases. As regard first course treatment, surgery is performed in 34.9% of the cases, radiotherapy in 60.4%, and chemotherapy in 32.2%. Fairly high incidence of lung carcinoma in man in Isere, contrasts with rather low incidence in woman, a situation rather different that the one in England and North America, where figures for women are slowly gaining over the one's for men.

[Epidemiology of testicular cancer]. / Epidémiologie des cancers du testicule.

Testicular carcinoma is a rare disease, with an incidence ranging from 0.2 (Blacks in Connecticut) to 7.8 (Denmark) in the World, and ranging from 2.5 to 4.3 in French Cancer Registries. An increase among young men has recently been described in Denmark and in England (Mortality Data between 1936 and 1976). Survival is 75% after five years, all histological types combined. No role as a risk factor "per se" has been confirmed for Genetics alone (Twins study in Finland), but a familial RR of 6 has been observed among first degree relatives of testicular carcinoma cases. Most interesting is a study by A.R. Moss, showing a RR of 4.4 among cases whose mother on had a breast cancer, as it emphasizes a possible role or hormones for non seminomatous testicular cancer.

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.