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Biomedical subjects

C Exbrayat

Publications and source records attributed to C Exbrayat.

At least 19 recordsLinked to original sources

Low doses of GM-CSF (molgramostim) and G-CSF (filgrastim) after cyclophosphamide (4 g/m2) enhance the peripheral blood progenitor cell harvest: results of two randomized studies including 120 patients.

The use of a combination of G-CSF and GM-CSF versus G-CSF alone, after cyclophosphamide (4 g/m2) was compared in two randomized phase III studies, including 120 patients. In study A, 60 patients received 5 x 2 microg/kg/day of G-CSF and GM-CSF compared to 5 mug/kg/day of G-CSF. In study B, 60 patients received 2.5 x 2 microg/kg/day G-CSF and GM-CSF compared to G-CSF alone (5 microg/kg/day). With the aim to collect at least 5 x 10(6)/kg CD34 cells in a maximum of three large volume leukapherises (LK), 123 LK were performed in study A, showing a significantly higher number of patients reaching 10 x 10(6)/kg CD34 cells (21/29 in G+GM-CSF arm vs 11/27 in G-CSF arm, P=0.00006). In study B, 109 LK were performed, with similar results (10/27 vs 15/26, P=0.003). In both the study, the total harvest of CD34 cells/kg was twofold higher in G-CSF plus GM-CSF group (18.3 x 10(6) in study A and 15.85 x 10(6) in study B) than in G-CSF group (9 x 10(6) in study A and 8.1 x 10(6) in study B), a significant difference only seen in multiple myeloma, with no significant difference in terms of mobilized myeloma cells between G-CSF and GM-CSF groups.

Adult↗

Optimizing the use of anti-interleukin-6 monoclonal antibody with dexamethasone and 140 mg/m2 of melphalan in multiple myeloma: results of a pilot study including biological aspects.

Interleukin-6 (IL-6) is a major survival factor for multiple myeloma (MM) cells preventing apoptosis induced by dexamethasone (DEX) or chemotherapy. In all, 24 consecutive patients with MM in first-line therapy received DEX for 4 days, followed by melphalan (HDM: 140 mg/m2) and autologous stem cell transplantation (ASCT). The anti-IL-6 monoclonal antibody (mAb) (B-E8) was given till haematological recovery, starting 1 day before DEX. Results were historically compared to MM patients treated with HDM 140 and 200 mg/m2. Our results show (1) that B-E8 was able to fully neutralize IL-6 activity in vivo before and after HDM as shown by inhibition of C reactive protein (CRP) production; (2) no haematological toxicity; (3) a significant reduction of mucositis and fever; (4) a median event-free survival of 35 months and an overall survival of 68.2% at 5 years with a median follow-up of 72 months; and (5) the overall daily IL-6 production progressively increased on and after 7 days post-HDM, with the increased serum CRP levels. In the 5/24 patients with uncontrolled CRP production, a large IL-6 production was detected (320 microg/day) that could not possibly be neutralized by B-E8. These data show the feasibility to neutralize IL-6 in vivo with anti-IL-6 mAb in the context of HDM.

Adult↗

Cancer incidence and mortality in France over the period 1978-2000.

BACKGROUND: Monitoring cancer incidence and mortality time trends is essential for cancer research and health-care planning. French cancer registries do not cover the entire population and do not provide a representative sample of the national population. Our study aimed at estimating national cancer incidence and mortality trends over the longest period available. METHODS: Incidence and mortality data were collected over the period 1978-1997. Twenty-seven cancer sites were selected and age, sex and site specific incidence and mortality rates were estimated for each year from 1978 up to 2000. Observed incidence and mortality data in the population covered by cancer registries were modelled using age-cohort methods. An estimation of the incidence/mortality ratio was obtained from these models and applied to the mortality rates predicted from an age-cohort model for the entire French population. The person-years of observation were calculated cohort-wise from census data provided by the national institute of statistics RESULTS: Cancer incidence increased by 63% throughout the study period, from 170,000 new cases in 1980 to 278,000 in 2000. This evolution was due to demographic changes but also to an increase in the risk of cancer which was estimated to more than 35% during the same period. In men, this change is largely explain by the increase of prostate cancer incidence. Among women, the increase was dominated by the continuing increase in breast cancer incidence. Large increases were also seen for non-Hodgkin lymphoma, melanoma, and thyroid cancer in both genders and for lung cancer in women. Cancer mortality increased by 20% from 125,000 deaths in 1980 to 150,000 in 2000. This increase is less than that predicted from changes in demographic factors and corresponds in fact to a decrease in the risk of death estimated to about 8%, slightly greater for women than for men. This decrease is associated with a decreasing incidence for stomach cancers for both sexes, alcohol-related cancer for men and cervical cancer for women. Colo-rectal cancer decreasing mortality contributes to this improvement despite an incidence increase. CONCLUSION: Between 1980 and 2000, the study showed a large change in the cancer burden both quantitatively and qualitatively. Decrease in exposure, earlier diagnosis and therapeutic improvement explained part of this change, but overall the distribution of cancer cases shifted toward a distribution including less aggressive cancers. A striking divergence between incidence and mortality trends is observed for a great number of cancers. Prostate cancer shares with breast cancer the same pattern of a severe increasing incidence and a stable mortality. This points to important changes in medical practice and needs further analysis. The trend of lung cancer mortality among women should be emphasised since the situation will inevitably worsen in the coming years. It is already the third cause of cancer death among women.

Age Distribution↗

[Estimate of regional prevalence of colorectal cancer in France].

BACKGROUND: Colorectal cancer prevalence is an important determinant of the health demand that completes information provided by cancer incidence. Current estimations established from data for the years 1985 and 1995 can be used to establish a precise description of changing healthcare needs for colorectal cancer. METHOD: Prevalence estimates method were based on incidence data computed on the regional scale by the FRANCIM network and mortality data provided by INSERM. We used the relationship that exists between the net risk of cancer, the net risk of dying of the given cancer and the age-specific prevalence of cancer. RESULTS: In 1995, the prevalence of patients who had a diagnosis of colorectal cancer amounted to 200 000 persons. The estimated number of prevalent cases was never lower than 3500 in any region and in 7 regions this number was higher than 10 000. From 1985 to 1995, there has been an increase of 35% in the prevalence rates. CONCLUSION: The evaluation of the number of persons who have had a diagnosis of colorectal cancer provides knowledge for health care planning. Such information on the regional scale is very useful for the health organisation (SROS). This geographical level induces difficulties not encountered at the national level.

Colorectal Neoplasms↗

Reduced intensity conditioning: enhanced graft-versus-tumor effect following dose-reduced conditioning and allogeneic transplantation for refractory lymphoid malignancies after high-dose therapy.

Non-myeloablative regimens have been proven to allow engraftment following allogeneic stem cells transplantation (allo-SCT) with minimal procedure-related toxicity. Conventional allo-SCT may produce remissions in patients with relapsed and refractory lymphoid malignancies (LM) but these good results may be achieved at the cost of high treatment-related morbidity and mortality. Application of allo-SCT using less intensive regimens may temper the frequency of these complications, allowing a potent graft-versus-tumor effect (GVT). We present our data on 11 patients with LM receiving allo-SCT with a reduced regimen. Ten patients had received previous high-dose therapy, and were at high risk for toxicity, thus precluding the use of allo-SCT. A fludarabine and low-dose busulfan combination facilitated engraftment while exerting GVT. Hematological recovery was quick, and full donor T cell chimerism preceded acute GVHD. GVHD and infections were the major problems. Spontaneous acute GVHD occurred in eight patients (72%). Five patients (45%) achieved complete remission, and the GVT effect was closely associated with GVHD. These results support the concept that GVT is effective against LM in patients who have been heavily pretreated. Further studies are needed to investigate strategies to generate more specific alloreactive effects providing optimal GVT and an acceptable risk of GVHD and infections.

Acute Disease↗

[Breast, cervical and colo-rectal simultaneous mass screening program for women 50 to 69 years old in Isere].

A cervical screening campaign is implemented in the Isere department since 1990 for women aged 50 to 69, together with breast cancer and colo-rectal cancer screening. The attendance rate is about 30% but a survey performed among this population shows that 68.6% of these women did presented for screening during the year following their invitation. One and a half per cent of all smears were abnormal or ASCUS smears. Cancer detection rate for invasive cancer and CIN III was 1.3/1000. General practitioners and gynaecologists took the same part in the programme. During a postal survey conducted among them, they declared that they felt concerned with cancer screening, even if they met some difficulties. This results suggest that nominative invitations and a good cooperation of GPs may improve the coverage of eligible women. For the future success of the National Programme, which is to be implemented in France, organisational arrangements have to be set up. The review of positive points and difficulties met by Isere's local programme may help to discuss it.

Aged↗

Analysis and classification of interval cancers in a French breast cancer screening programme (département of Isère).

The objective of this study is to analyse detection rates and stage of diagnosis of interval cancers in the mass screening mammography programme of Isère (France), launched in 1990. Interval cancers are defined as breast cancers diagnosed within 30 months after a negative screening assessment, for women attending the programme between November 1990 and December 1994. Stages of diagnosis of these cancers are compared with those of screened cancers and to those of cancers diagnosed outside the programme. The rates of invasive interval cancers are 17.7% of the expected incidence rate during the first year, 60.0% during the second year and 58.8% after the second year. Sensitivity of the programme (one test every 30 months) is 74%; sensitivity at one year is 82%. Results are better for women aged 60-69 years than for younger women (50-59 years). Diagnosis is made at an early stage with 8% of in situ cases, and with 40% of very small tumours (sizes < or = 10 mm). Those stages are very close to the ones for screened cases. Interval cancer rates are low during the first year. Higher rates for the second year and early stages of diagnosis could be explained by self-referred screening practice in our area.

Age Distribution↗

[Patterns of health care delivery and breast cancer in the department of Isère in 1955].

BACKGROUND: Caring for cancer patients is expensive, warranting verification that health care organization works in a satisfactory way. A first step of this evaluation deals with the description of the pathway followed in the health care system by the patient. METHODS: 671 breast cancer cases were diagnosed in Isère in 1995. According to the place where each treatment (surgery, chemotherapy, radiotherapy) was performed, we described pathways for the patient, either entirely private, public or mixed. Characteristics of the patient (age, place of residence), of the disease (extent of disease, way of discovery) and of the physician (general practitioner, specialist) might have influenced the choice of this pathway. We described and tested the distribution of these characteristics within the 3 groups using univariate analysis. Relative risk of being affected to the private pathway compared to the public one was computed, after adjusting for age, type of physician, extent of disease, way of discovery and sanitary area, using a multivariate analysis (logistic regression). RESULTS: In the department of Isère, the private pathway cared for 55% of breast cancers, the public one 23% and the mixed one 19%. There was no preferential recruitment according to age, physician type, presence of metastasis or of the rural or urban residence. In sanitary area number 5, characterized by an important attraction of the patients by the nearby department of Rhône, 41% of the patients were cared for the private pathway, compared to 63% in sanitary area 4, where most patients were treated in the main town of Isère: Grenoble. After early breast cancer detection with mammography instead of breast cancer screening, probability of being cared for in the private pathway was 2-fold higher (OR = 2) than in the public one. CONCLUSION: In Isère department, early breast cancer detection with mammography is in favor of the private pathway. This is not true for physician type, neither for characteristics of the patient or extent of the disease. Finally, the distance to next department of oncology or radiotherapy plays a major role.

Aged↗

Influence of the 'directions for use' on positivity rates of the Hemoccult II test.

OBJECTIVE: A concise, detailed, and complete instruction sheet is indispensable for adequate completion by the users of a product. This sheet should be enclosed in the envelope which contains Hemoccult II slides. The authors found that the instructions provided by the French manufacturer were unsatisfactory. They designed a short and simple notice, adequately detailed to be understandable by all volunteers and to obtain satisfactory stool smears. Positivity rates of Hemoccult II performed with the manufacturer's notice were compared to those obtained with Hemoccult II performed with the authors' instructions. METHODS: This study was made during the third screening campaign carried out by the Office Departemental de Lutte contre le Cancer (ODLC). This screening programme only concerned women 59 to 69 years of age. Six thousand three hundred and ninety-two Hemoccult II containing the manufacturer's instructions were received at the laboratory during March, April, May, June and July 1996, and 2633 Hemoccult II containing the ODLC instructions during March, April, May, June and July 1997. All Hemoccult II were developed and read by one trained technician in the Biochemistry Laboratory (Grenoble University Hospital). RESULTS: The two populations, studied in 1996 and 1997, were strictly comparable in terms of age and number of previous screenings. Out of 6392 Hemoccult II containing the manufacturer's instructions, 157 (2.5%) were found positive, as compared to 36 (1.4%) Hemoccult II out of 2633 which contained the authors' instructions. This difference is highly significant (P = 0.001). CONCLUSION: The directions for use provided with Hemoccult II had a crucial influence on positivity rates, and therefore on the cost of screening. The instruction sheet provided by the French manufacturer is not satisfactory as it contains too much needless information, while several important pieces of advice are missing.

Aged↗

Mass screening programs for breast cancer in France--average values of assessment criteria.

Breast cancer is the most common cancer in women worldwide. Many studies have been performed worldwide to assess the effectiveness of screening in terms of reduced mortality due to breast cancer. Since the end of 1989, 10 breast cancer mass screening programs using mammography have been carried out in France under the sponsorship of the National Fund for Health Prevention, Education, and Information (FNPEIS) from the National Health Insurance of Salaried Workers (CNAMTS). These 10 campaigns, which are on a district scale, are organized according to variable methods and are assessed using a common procedure. Four groups of criteria are measured in this procedure, which investigates the impact, quality, effectiveness, and costs of screening programs. The average and extreme values of each criterion as calculated from the campaigns are presented in this paper. In order to enlighten the judgment on the French results, a comparison with the international standards in force and with the results of foreign screening programs is proposed.

Aged↗

[Prevalence assessment of colorectal and breast cancers in the Rhône-Alpes area].

Prevalence of malignant neoplasm is a basic health indicator used in order to evaluate needs in medical equipment for treatment and follow-up of cancer patients. Data on prevalence are regularly published by Northern European countries. Thames and Connecticut cancer registries. In France available information on prevalence are scanty, because follow-up of cancer patients is not easy. Therefore, we used a statistical method to evaluate prevalence from incidence and mortality in the Rhône-Alpes area (France, 5,300,000 inhabitants) in 1990, using the department of Isère population based registry. For females, figures for breast carcinoma and colorectal carcinoma are respectively 25,000 and 5,700, and, for males, 5,700 colorectal carcinoma. For 5 year partial prevalence, these figures are respectively 11,300, 3,100 and 3,500. The ratio prevalence/incidence is 8.9 for breast in females, 5.8 for colorectal carcinoma in females and 4.8 for colorectal carcinoma in males with a steep decrease for 5 year partial prevalence (4 for breast carcinoma, 3.1 for females colorectal carcinoma and 2.9 for males colorectal carcinoma). These ratios are consistent with those observed elsewhere in Europe.

Adult↗

Use of mammography as a breast cancer screening tool in six districts in France.

Mass screening programs to detect breast cancer are currently under way in many countries. In France, several districts have been running mammographic screening programs since 1989. A survey was conducted in five of these districts and in a sixth district where no screening program was implemented. Using a self-addressed questionnaire mailed to a sample of 1500 women aged over 20 years, the survey was aimed at assessing women's use of mammography as well as their knowledge and perception of mammographic breast cancer screening. According to district, the compliance of the women replying to the questionnaire ranged from 72 to 82%. The proportion of women who had at least one mammography during their life ranged from 41 to 54%, according to district. The percentage of women aged 50 to 69 who had one mammography within 3 years before the survey ranged from 57 to 78% in the experimental districts and was only 48% in the control district. In all districts, women did not know exactly at what age it is recommended to start screening and with what periodicity, but, when invited to do so, they were satisfied with the program and intended to participate again.

Adult↗

[Campaign for cervical cancer screening with vaginal smears in women aged 50-69 years in Isère (France). Results of the first round (January 1991-June 1993)].

The department of Isère, which is involved since 1990 in a breast cancer screening campaign concerning women aged 50 to 69, has managed to associate a cervical and colorectal cancers screening program. The target sample size is 98,000 individuals. Women are asked to refer their general practitioner or gynaecologist for cervicovaginal smears. Each woman is invited at a screening interval of 30 months. The results of the first invitation (November 1990-December 1992) are reported. Thus 29,570 women did referred, so that the screening uptake is 30% and 20,083 women (68%) had Pap smears inside the screening program. 1.1% of the smears were unsatisfactory and 1.2% of the tests showed abnormalities. Ninety-six percent of the women who had been referred for further examinations have been followed up. Thirty-eight women (representing 17% of smears with abnormalities) had surgery (conisation, hysterectomy, Wertheim). Among them, 5 cases of invasive cervical carcinoma and 25 in situ carcinoma were detected. The detected cancer prevalence per 1,000 women screened is 1.5/1000. An organised screening program for cervical cancer in association with breast cancer screening, seems to be an effective way of increasing smears realisation in women aged 50 to 69, and of involving general practitioners in cervical cancer screening.

Aged↗

[Mass screening programs for breast cancer in France. Comparative evaluation].

OBJECTIVE: The purpose of this work was to comparatively assess the results of mass screening programs for breast cancer implemented in six French departments in 1986, within the scope of the National Fund for Health Prevention, Education and Information of the National Health Insurance Office of Salaried Workers. MATERIAL AND METHODS: The data collected by the screening centres were analyzed by ten assessment teams that were independent from the program promotion staff, all using the same evaluation form. A complementary population study performed in eight French districts then, allowed assessing the frequency of self-referred screening (mammography performed out of program). RESULTS: The rate of participation in screening programs, in relation to the invited population, ranged from 21 to 48%, according to the district (36% in average). This low participation was probably related to the extent of self-referred screening. In fact, 19 to 40% of women, according to the district, had previously had a screening mammographic coverage: rate was around 68% in women aged 50 to 69 years. Positive findings with mammography ranged from 4.5 to 15.8% (10.1% in average), while intervention rates ranged from 0.7 to 1.6% and detection rates from 3.8 to 6.2%. The ratio between benign tumors and cancers ranged from 0.7 to 2.1 according to the district. In order to enlighten the judgement on French results, we propose a comparison with the international standards in force. CONCLUSION: The various experiences with breast cancer screening in France show that this screening is technically feasible on the basis of existing medical structures. However, some criteria are still below the expected values, especially if compared with international standards. This result is probably accounted for by the high rate self-referred screening before age 40 in France. In these conditions, the question is whether extending breast cancer screening programs in France is an appropriate course of action.

Breast Neoplasms↗

Multiple primary cancers and estimation of the incidence rates and trends.

The use of different registration rules from one registry to another, both generally and also for paired organs, leads to variations in the proportion of multiple primary cancers: in men, from 0.4 to 4.9% for the colon, 0.1 to 2.7% for the lung, and 4.1 to 8.6% for the mouth and pharynx. Subjective factors, often impossible to verify, contribute to these variations. The impact on the estimation of incidence rates and trends is not negligible for cancers of the mouth and the pharynx and for all the cancers taken together. The trend towards an increase of cancers of the mouth and pharynx in the Bas-Rhin disappeared when the incidence was expressed taking only the first cancer (incidence by individual) into consideration, and the differences in incidence between the Calvados and the Bas-Rhin registries for the same site also disappeared. In the absence of harmonisation of the rules and methods followed for registration, incidence by individual is the only approach which makes it possible to compare incidence rates and trends between registries.

Breast Neoplasms↗

[Simultaneous screening of cancers of the breast, cervix, colon and rectum. The Isère experience].

The mass screening program for cancer in the Isere department offers women between 50 and 69 years a medical consultation and three tests: mammography for breast cancer screening, Pap smear for cervical cancer screening, and hemoccult for colorectal cancer. During the first round, 29,570 women took part in the program, 21% had a mammography, 20% Pap smears and 25% a hemoccult. In breast cancer screening, the rate for further examination was 11.9%, the breast cancer detection rate was 5.4 per 1,000 women screened and the detection rate of invasive tumor < or = 10 mm: 2.0 per 1,000. In cervical cancer screening, the rate of abnormal examinations was 1.2%. The cervical cancer detection rate was 1.5 per 1,000. The rate of positive hemoccult was 2.7% and the rate of colorectal cancers and polyps 10 mm or larger was 2.7 per 1000. Results of screening are satisfying, but compliance rate is too low. Acceptance rate must be examined in following rounds.

Aged↗