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Objectives: To describe the ovarian cancer incidence and mortality trends in France from 1980 to 2000., Materials and Methods: Incidence data were obtained from 9 French departments covered by cancer registries which systematically record all cancers, of which those of the ovary. Mortality data has been provided by INSERM bureau in charge of the analysis of death certificates., Results: With 4500 incident cases and 3500 deaths for the year 2000 in France, ovarian cancer still shows a poor prognosis. Age adjusted incidence and mortality rates are almost stable over the study period at an annual rate of 9 by 100000 for incidence and 5.5 by 100000 for mortality. However the risk of developing this cancer and the risk of dying from it, steadily decreased for the cohort born in 1930 to 1950, and the beginning of this reduction corresponds exactly to the beginning of oral contraception. We present comparisons between departments and analyze the border-line tumors in parallel with invasive cancers., Conclusion: The cancer of the ovary represents only a small part of female cancers (3.8%) in France and its incidence is stable over time, but its prognosis is very bad.

Addition of chemotherapy to the treatment of non-small-cell lung cancer (NSCLC) resulted in a modest but clear improvement in the survival of selected patients. To ascertain if this translates to improved survival in the whole population of patients, we conducted a retrospective population-based study of a sample of 1738 patients diagnosed with primary NSCLC in a French department between 1982 and 1997. The proportion of women, metastatic cases and adenocarcinoma changed significantly over time, as did their management: use of chemotherapy alone increased from 9.7 to 28.1% (P<0.0001), while the use of radiotherapy alone decreased from 32.2 to 9.4% (P<0.0001). The 5-year survival probability was 15.7 % for all patients and 32.6% for those with resectable disease. The 1- and 2-year survival probabilities were 38.2 and 15.6% in locally advanced disease, and were, respectively, 16.8 and 5.2% in metastatic disease. Disease extent and histological subtype were significant independent prognostic factors. Survival of resectable disease was longer among patients treated with surgery or surgery plus chemotherapy, while better outcomes for locally advanced disease were associated with radiation plus chemotherapy. In metastastic disease, patients treated by classical agent without platin or palliative care only had the shortest survival. Despite changes in treatment in accordance with the state-of-the-art, overall survival did not improve over time. It is not unlikely that more patients with bad PS were diagnosed during the latter end of the study period. This could at least partially explain the absence of detection of an overall improvement in survival.

Initiation and re-initiation of chromosomal DNA replication in bacteria rely on divergent multiprotein assemblies, which direct the functional delivery of the replicative helicase on single-stranded DNA (ssDNA) at specific sites. These two processes are triggered either at the single chromosomal origin oriC or at arrested forks by the conserved DnaA and PriA proteins respectively. In Bacillus subtilis, these two pathways further require the three essential proteins DnaB, DnaD and DnaI, restrictively encoded in Gram positive bacteria of low GC content. We have recently shown that DnaI and DnaB act as a pair of loaders of the DnaC replicative helicase. The role of DnaD appeared more enigmatic. It was previously shown to interact with DnaA and to display weak ssDNA binding activity. Here, we report that purified DnaD can interact physically with PriA and with DnaB. We show that the lethality of the temperature-sensitive dnaD23 mutant can be suppressed by different DnaB point mutants, which were found to be identical to the suppressors of priA null mutants. The DnaD23 protein displays lower ssDNA binding activity than DnaD. Conversely, the DnaB75 protein, the main dnaD23 suppressor, has gained affinity for ssDNA. Finally, we observed that this interplay between DnaD and DnaB is crucial for their concerted interaction with SSB-coated ssDNA, which is the expected substrate for the loading of the replicative helicase in vivo. Altogether, these results highlight the need for both DnaD and DnaB to interact individually and together with ssDNA during the early stages of initiation and re-initiation of chromosomal DNA replication. They also point at a main structural role of DnaD in the multiprotein assemblies built during these two essential processes.

The purpose of this study was to assess possible regional disparities in the management of colon cancer in France. In 1995, 1605 patients with a colon cancer in eight areas covered by a population-based cancer registry were studied. Pre-therapeutic work-up, stage at diagnosis and therapeutic modalities were assessed. There were no differences between areas concerning the resection or the stage at diagnosis. The proportion of patients with a colonoscopy alone varied between 42.7 and 70.4% (P<0.001). The use of both colonoscopy and barium enema was even more heterogeneous (extremes from 11.7 to 40.2%, P<0.001). There were significant differences in the performance of abdominal computed tomography and tumour markers. The number of examined lymph nodes was lower than the recommendation in 47.3% of cases with extremes ranging from 36.9 to 60.9%. Adjuvant chemotherapy was performed on average in 49.4% of cases in stage II (in which it is not recommended) with extremes from 18.8 to 72.5% (P<0.001) and in 79.6% of the cases in stage III (in which it is recommended) with extremes from 63.6 to 94.4% (P=0.08). In conclusion, these results should alert practitioners and health care authorities in order to homogenize practices.

Background: In France, cancer ranks third as the most significant cause of mortality in young people. However, the incidence, the survival, and the management of adolescent cancers have never been studied. The aim of this study is to investigate incidence rate (IR) of adolescents with cancer from data recorded in French Cancer Registries covering eight administrative areas, representing 10% of the French population, over a 10-year period (from 1988 to 1997)., Procedure: Data from the FRANCIM network of French population-based Cancer Registries were used to analyze cancer incidence among adolescents aged from 15 to 19 years, excluding basal cell carcinomas of skin., Results: In total, 699 cases were recorded. Of these, 22.9% were lymphomas, 12.7% germ-cell tumors, 11.9% leukemias, 10.6% central-nervous-system tumors, 10.0% bone neoplasms, 7.6% soft-tissue sarcomas, and 19.5% tumors of adulthood (thyroid carcinomas 4.9%, melanomas 9.0%, and other carcinomas 5.6%). The overall IR was 172.9 per million adolescents (M/F: 1.2) with an annual increase of 3% (P = 0.58). Over the two 5-year periods (1988-1992 and 1993-1997) the IR increases significantly for malignant melanomas (respectively 10.4 and 21.2; P = 0.04)., Conclusions: Our findings are similar to that reported by previous studies performed in European and North-American countries. Future studies need to focus on the etiology explaining the increase in incidence, the management and the impact of the type of care on outcomes., (2004 Wiley-Liss, Inc.)

Aim: Monitoring cancer incidence and time trends is essential for cancer research and health care planning. The aim of the study was to compare the incidence of gastrointestinal cancers in twelve administrative area in France to estimate the national cancer incidence during 2000 compared with the preceding 20 years., Methods: Incidence data was provided by cancer registries and mortality data by the French national medical research institute (INSERM). The two data sets were modeled separately over the period 1988-1997 using age-cohort models. The incidence/mortality ratio obtained from these models was applied to the mortality rates of an age-cohort model of the entire population., Results: The estimated number of new cases of gastrointestinal cancer was 61,465 in 2000. Colorectal cancer was the leading localization with 36,257 cases. The incidence of gastrointestinal cancers was slightly higher in northern than in southern area. Incidence of esophageal cancer was three times that of liver cancer. Variations in incidence were less marked for other localizations. The incidence of gastric and esophageal cancer in the male population decreased between 1980 and 2000, on average by slightly more than 2% per year. Incidence of other cancers increased. The number of new cases of colorectal cancer increased by 50%. The rise in the incidence of liver cancer was particularly striking, with an increase from 2000 incident cases in 1980 to nearly 6000 in 2000., Conclusion: For most localizations, incidence of gastrointestinal cancers displays few geographical differences in France, but there has been a striking change in incidence trends over the past 20 years.

The epidemiology of cancers is known in France through mortality data provided by Inserm and morbidity data obtained by French tumor registries. The purpose of this study was to compare the incidence of laryngeal cancers in 9 French departments and to give an estimate of this incidence for the whole of France, based on this data. Incidence and mortality data were collected over the period 1978-1997. The 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 estimated number of laryngeal cancers was 3,865 in males and 361 in females. There were pronounced contrasts in laryngeal cancer incidence between cancer registries. The incidence rate of laryngeal cancers were especially high in the Somme and Calvados department compared to those observed in Haut-Rhin and Tarn. The ratio incidence/mortality was 2.4 in Doubs and 1.3 in Somme. France is among the countries which have the highest rates of incidence and mortality for laryngeal cancer in Europe.

Background: Population-based registries provide excellent data for drawing an accurate picture of disease management practices. The purpose of this study was to determine whether diagnostic and therapeutic management practices for rectal cancer vary in different geographic regions of France., Methods: Data Issued from nine cancer registries covering 11% of the French population. The files of 683 patients with a rectal cancer diagnosed in 1995 were selected for analysis., Results: Colonoscopy was performed in a mean of 91.6% of patients (range: 80.9%-98.2%) (P=0.01). The practice of colonoscopy concomitantly with barium enema varied greatly, ranging from 1.9%-57.7% of patients (P<0.001). Pretherapeutic work-up practices were significantly different depending on the region with respect to: abdominal CT scans (13.4%-69.2%), thoracic CT scans (0.9%-13.2%) and tumor markers (46.8%-80.8%). There were no significant differences between geographic regions concerning rate of resection, use of colostomy, or tumor stage at diagnosis. Administration of adjuvant radiotherapy (mean, 46.8%; range: 21.6%-70%; P<0.001) and adjuvant chemotherapy (mean, 24.1%; range: 10.3%-40.6%; P<0.05) varied significantly between regions., Conclusion: Diagnostic practices and administration of adjuvant treatments vary significantly between geographic regions in France. The recommendations of the French consensus guidelines are only partially adhered to. Practitioners and healthcare Authorities should be aware of these differences in order to provide more harmonious patient care.

The aim of this study was to evaluate the predictive value of five different biological factors in breast cancer patients treated with neoadjuvant anthracycline-based chemotherapy: (1) tumour grade scored according to the Elston-Ellis classification, (2) hormonal receptor (HR) status; (3) tumour cell proliferation evaluated by Ki-67 staining, (4) HER-2 and topoisomerase II alpha (TopoIIalpha) expression evaluated by immunohistochemistry (IHC), (5) HER-2 and TopoIIalpha amplification evaluated by real-time polymerase chain reaction (PCR). 119 patients with operable breast cancer were treated with six cycles of FEC (100 5-fluorouracil (5-FU) 500 mg/m2, Epirubicin 100 mg/m2, Cyclophosphamide 500 mg/m2). Tumour response was assessed clinically and by computed tomography (CT) scan, then by pathological assessment. The clinical overall response (OR) was 80%, with 19% of complete responders (CR). The radiological OR was 71%, with 16% of CR. A pathological CR was demonstrated in 13% of the patients according to the Sataloff classification. In the multivariate analysis, the absence of HR expression and Ki-67 > or = 20% were predictive for a clinical CR. A high tumour grade was predictive for a pathological CR. Overexpression or amplification of HER2 or Topollcalpha were not predictive of response.

Non-medical factors influencing treatment choices in prostate cancer are not well understood. We carried out a population-based study to obtain information on the management of prostate cancer patients. Our study population consisted of 1000 men diagnosed during 1995 from five French cancer registries. We looked at the main treatments performed in the year following diagnosis. Multivariate analysis was used to describe the determinants of the various treatment choices, simultaneously taking into account medical and non-medical factors. The probability of treatment by radical prostatectomy (RP) was 3 times higher in the Tarn area, whereas in the Calvados area the probability of treatment by radiotherapy was almost 6 times higher. The private sector favoured radical prostatectomy and hormonal therapy. In France, as in other developed countries, the initial treatment of prostate cancer varies greatly according to non-medical factors. This type of investigation, if carried out regularly, would make it possible to evaluate changes in practice patterns.

Objective: To summarize the geographical and temporal variations in incidence of pleural mesothelioma in Europe, using the extensive data available from European general cancer registries, and consider these in light of recent trends in asbestos extraction, use and import in European countries., Material and Methods: The data were extracted from the European Cancer Incidence and Mortality database (EUROCIM). The inclusion criteria was acceptance in Volume VII of Cancer Incidence in Five Continents. Truncated age-standardized rates per 100,000 for the ages 40-74 were used to summarise recent geographical variations. Standardized rate ratios and 95% confidence intervals for the periods 1986-1990 and 1991-1995 were compared to assess geographical variations in risk. To investigate changes in the magnitude of most recent trends, regression models fitted to the latest available 10-year period (1988-1997) were compared with trends in the previous decade. Fitted rates in younger (40-64) and older adults (65-74) in the most recent period were also compared., Results: There was a great deal of geographical variation in the risk of mesothelioma, annual rates ranging from around 8 per 100,000 in Scotland, England and The Netherlands, to lower than 1 per 100,000 in Spain (0.96), Estonia (0.85), Poland (0.85) and Yugoslavia, Vojvodina (0.56) among men. The rank of the rates for women was similar to that observed for men, although rates were considerably lower. Between 1978 and 1987, rates in men significantly increased in all countries (excepting Denmark). In the following 10 years, there was a deceleration in trend, and a significant increase was detectable only in England and France. In addition, the magnitude of recent trends in younger men was generally lower than those estimated for older men, in both national and regional cancer registry settings., Conclusions: While mesothelioma incidence rates are still rising in Europe, a deceleration has started in some countries. A decrease may begin in the next few years in certain European populations considering the deceleration of observed trends in mesothelioma and asbestos exposure, as well as the recent ban on its use.

The delivery of a ring-shaped hexameric helicase onto DNA is a fundamental step of DNA replication, conserved in all cellular organisms. We report the biochemical characterization of the bacterial hexameric replicative helicase DnaC of Bacillus subtilis with that of the two replication initiation proteins DnaI and DnaB. We show that DnaI and DnaB interact physically and functionally with the DnaC helicase and mediate its functional delivery onto DNA. Thus, DnaB and DnaI form a pair of helicase loaders, revealing a two-protein strategy for the loading of a replicative helicase. We also present evidence that the DnaC helicase loading mechanism appears to be of the ring-assembly type, proceeding through the recruitment of DnaC monomers and their hexamerization around single-stranded DNA by the coordinated action of DnaI and DnaB.

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.

This article analyses time trends and geographical variations of thyroid cancer by histological type. Incidence data were provided by 8 French cancer registries over the period 1978-1997, with 3853 adult cases reported. To assess the effects of age, period, cohort and area on incidence, log-linear Poisson regression models were used. Thyroid cancer increased exponentially from the cohort born in 1925. This increase was essentially due to papillary cancer, which increased by 6.2% per year in men and 8.1% per year in women over the entire period (1978-1997). In women, the recent trends were significantly different between the studied geographical areas. The analysis shows that the increase in thyroid cancer, essentially of the papillary type, is not recent. It may be attributed to a possible screening effect or to an increase in the number of "incidentally" discovered cases linked to the use of modern diagnostic tools.

The PriA protein was identified in Escherichia coli as a factor involved in the replication of extrachromosomal elements such as bacteriophage phiX174 and plasmid pBR322. Recent data show that PriA plays an important role in chromosomal replication, by promoting reassembly of the replication machinery during reinitiation of inactivated forks. A gene encoding a product 32% identical to the E.coli PriA protein has been identified in Bacillus subtilis. To characterise this protein, designated PriA(Bs), we constructed priA(Bs) mutants. These mutants are poorly viable, filamentous and sensitive to rich medium and UV irradiation. Replication of pAMbeta1-type plasmids, which is initiated through the formation of a D-loop structure, and the activity of the primosome assembly site ssiA of plasmid pAMbeta1 are strongly affected in the mutants. The purified PriA(Bs) protein binds preferentially to the active strand of ssiA, even in the presence of B.subtilis SSB protein (SSB(Bs)). PriA(Bs) also binds stably and specifically to an artificial D-loop structure in vitro. These data show that PriA(Bs) recognises two specific substrates, ssiA and D-loops, and suggest that it triggers primosome assembly on them. PriA(Bs) also displays a single-stranded DNA-dependent ATPase activity, which is reduced in the presence of SSB(Bs), unless the ssiA sequence is present on the ssDNA substrate. Finally, PriA(Bs) is shown to be an active helicase. Altogether, these results demonstrate a clear functional identity between PriA(Ec) and PriA(Bs). However, PriA(Bs) does not complement an E.coli priA null mutant strain. This host specificity may be due to the divergence between the proteins composing the E.coli and B.subtilis PriA-dependent primosomes.

Background: Axillary lymph node involvement (ALNI) remains the most accurate predictive factor for recurrence risk and survival in patients with invasive breast carcinoma (IBC) and is an essential element in therapeutic decisions. However, axillary dissection (AD) is responsible for several side effects and is now discussed in small IBC. The objective of this study was to define a predictive model of ALNI by using clinical and histologic variables available before surgery., Methods: The authors studied 795 cases of IBC (T0, T1, T2 < or = 4 cm; N0; M0) treated between 1980 and 1997 by conservative surgery and radiation therapy. All cases had axillary dissection with at least 10 lymph nodes removed. A stepwise logistic regression analysis was performed to build a predictive model of ALNI. The authors then used the jackknife resampling technique to produce unbiased estimates of the probabilities of ALNI along with their confidence intervals., Results: The global ALNI rate was 25.7%. The final predictive model included clinical tumor size, location, and histologic subtype and grade as variables independently associated with ALNI. The estimated probability of ALNI varied from 6% to 45%, according to case characteristics for these variables., Conclusions: These results show that the omission of AD in surgical procedures for these tumors is debatable. Even when ALNI rates were low, the superior bounds of the confidence intervals could be high. Consequently, we do not recommend to omit AD in women whose estimated risks are higher than 25%. Women with a risk of ALNI lower than 25% could benefit from the sentinel lymph node procedure with, likewise, a limited risk of false-negative.

The domain structure of the HSC70-interacting protein (HIP), a 43-kDa cytoplasmic cochaperone involved in the regulation of HSC70 chaperone activity and the maturation of progesterone receptor, has been probed by limited proteolysis and biophysical and biochemical approaches. HIP proteolysis by thrombin and chymotrypsin generates essentially two fragments, an NH2-terminal fragment of 25 kDa (N25) and a COOH-terminal fragment of 18 kDa (C18) that appear to be well folded and stable as indicated by circular dichroism and recombinant expression in Escherichia coli. NH2-terminal amino acid sequencing of the respective fragments indicates that both proteases cleave HIP within a predicted alpha-helix following the tetratricopeptide repeat (TPR) region, despite their different specificities and the presence of several potential cleavage sites scattered throughout the sequence, thus suggesting that this region is particularly accessible and may constitute a linker between two structural domains. After size exclusion chromatography, N25 and C18 elute as two distinct and homogeneous species having a Stokes radius of 49 and 24 A, respectively. Equilibrium sedimentation and sedimentation velocity indicate that N25 is a stable dimer, whereas C18 is monomeric in solution, with sedimentation coefficients of 3.2 and 2.3 S and f/f(o) values of 1.5 and 1.1 for N25 and C18, respectively, indicating that the N25 is elongated whereas C18 is globular in shape. Both domains are able to bind to the ATPase domain of HSC70 and inhibit rhodanese aggregation. Moreover, their effects appear to be additive when used in combination, suggesting a cooperation of these domains in the full-length protein not only for HSC70 binding but also for chaperone activity. Altogether, these results indicate that HIP is made of two structural and functional domains, an NH2-terminal 25-kDa domain, responsible for the dimerization and the overall asymmetry of the molecule, and a COOH-terminal 18-kDa globular domain, both involved in HSC70 and unfolded protein binding.

Breast helical computed tomography (CT) was evaluated for use in assessing response to neoadjuvant chemotherapy and residual tumor volume. Forty-three patients with large, inflammatory breast cancers (stage IIA, 12; IIB, 13; IIIA, 9; IIIB, 9), all histologically confirmed by core biopsy, were evaluated prior to and following neoadjuvant chemotherapy. The breast helical CT procedure involved patients in the prone position using single acquisition during quiet respiration following intravenous injection of nonionic contrast material. Helical CT results (3.2-mm slices and maximum intensity projections) were compared to clinical and mammographic evaluations, as well as to pathologic findings. All tumors were clearly visible by breast helical CT, showing important tumor enhancement. Helical CT evaluation of response to chemotherapy (using World Health Organization criteria) corresponded better with mammography (78%, Cohen's kappa statistic (kappa) = 0.65) than with clinical examination (53%, kappa = 0.30). Helical CT measurement of residual tumor volume after neoadjuvant chemotherapy and correlation with pathologic findings were globally satisfactory. The intraclass correlation coefficient was 0.69 (excellent for rounded opacities [0.97], but not as good for diffuse, scattered or multinodular opacities [0.60]). By contrast, clinical and mammographic correlations were globally unsatisfactory (0.49 and 0.28, respectively). Breast helical CT can be very useful in the quantitative assessment of response to neoadjuvant chemotherapy and preoperative determination of residual tumor volume. For this reason, it can be considered an alternative to breast magnetic resonance imaging because of its simplicity, rapidity, and accessibility.

Purpose: To analyze the main determinants of lymph nodal recurrence in early breast cancer and to compare our results with literature data., Methods: Retrospective analysis of 1119 patients with stage I-II infiltrating breast cancer treated by conservative radiosurgical association from 1980 to 1992, with a 10-year median follow-up., Results: The global rate of lymph nodal recurrence (LNR) was 2.7% (30 cases). Age under 40, high histoprognostic grade and previous local recurrence were the main risk factors of LNR. Axillary nodal involvement at time of diagnosis, number of lymph nodes sampled and tumor localization were not significantly related to LNR., Conclusion: Lymph nodal recurrences of early breast cancers are not frequent, but their prognosis is very unfavourable. A multidisciplinary approach of these LNR is necessary, taking into account previous treatments.

Purpose: To assess the clinical and histological characteristics of breast cancer (BC) occurring after Hodgkin's disease (HD) and give possible therapies and prevention methods., Materials and Methods: In a retrospective multicentric analysis, 117 women and two men treated for HD subsequently developed 133 BCs. The median age at diagnosis of HD was 24 years. The HD stages were stage I in 25 cases (21%), stage II in 70 cases (59%), stage III in 13 cases (11%), stage IV in six cases (5%) and not specified in five cases (4%). Radiotherapy (RT) was used alone in 74 patients (63%) and combined modalities with chemotherapy (CT) was used in 43 patients (37%)., Results: BC occurred after a median interval of 16 years. TNM classification (UICC, 1978) showed 15 T0 (11.3%), 44 T1 (33.1%), 36 T2 (27.1%), nine T3 (6.7%), 15 T4 (11.3%) and 14 Tx (10.5%). Ductal infiltrating carcinoma and ductal carcinoma in situ (DCIS) represented 81.2 and 11.3% of the cases, respectively. Among the infiltrating carcinoma, the axillary involvement rate was 50%. Seventy-four tumours were treated by mastectomy without (67) or with (ten) RT. Forty-four tumours had lumpectomy without (12) or with (32) RT. Another four received RT alone, and one CT alone. Sixteen patients (12%) developed isolated local recurrence. Thirty-nine patients (31.7%) developed metastases and 34 died; 38 are in complete remission whereas five died of intercurrent disease. The 5-year disease-specific survival rate was 65.1%. The 5-year disease-specific survival rates for the pN0, pN1-3 and pN>3 groups were 91, 66 and 15%, respectively (P<0.0001), and 100, 88, and 64% for the TIS, T1 and T2. For the T3 and T4, the survival rates decreased sharply to 32 and 23%, respectively. These secondary BC are of two types: a large number of aggressive tumours with a very unfavourable prognosis (especially in the case of pN>3 and/or T3T4), and many tumours with a 'slow spreading' such as DCIS and microinvasive lesions. These lesions developed especially in patients treated exclusively by RT., Conclusions: The young women and girls treated for HD should be carefully monitored in the long-term by clinical examination, mammography and ultrasonography. We suggest that a baseline mammography is performed 5-8 years after supradiaphragmatic irradiation (complete mantle or involved field) in patients who were treated before 30 years of age. Subsequent mammographies should be performed every 2 years or each year, depending on the characteristics of the breast tissue (e.g. density) and especially in the case of an association with other BC risk factors. This screening seems of importance due to excellent prognosis in our T(1S)T(1) groups, and the possibility of offering these young women a conservative treatment.

Background: An attempt was made to improve metachronous oesophageal cancer prognosis through bi-annual systematic esophageal endoscopy screening in patients treated for head and neck cancer., Patients and Methods: Bi-annual esophageal endoscopy, without a staining procedure, was performed in 1560 patients from 1987 to 1997. The distribution of previous head and neck cancer was oral cavity (20%), oropharynx (30%), hypopharynx (34%), and larynx (16%). All patients had initial panendoscopic inspection before HNSCC treatment. Esophageal tumors were considered to be second synchronous primaries when discovered within the first six months of initial tumor diagnosis., Results: Fifty metachronous esophageal asymptomatic cancers (42 T1 and 7 in situ carcinomas) were diagnosed by endoscopy. The median time between the HNC and the esophageal carcinoma was 43 months (7-137 months). Metachronous esophageal carcinoma was discovered in 2.6% of patients with oral cavity tumor, 5.7% of patients with oropharynx tumor, 2.3% of patients with hypopharynx tumor, and 1.7% of patients with larynx tumor. Causes of death were: 41.1% related to esophageal tumor with tumor progression, metastatic evolution, or treatment toxicity; 28.9% related to non malignant causes; 26.6% related to a cancer that was not of esophageal origin., Conclusions: Over a 10-year period, systematic bi-annual esophageal endoscopy uncovered metachronous esophageal tumors in 3.2% of 1560 patients originally treated for head and neck carcinoma, developing in a median time of 47 months. Patients with initial oropharyngeal tumors had a significantly higher risk of metachronous esophageal SCC, compared to the other tumor sites (P < 0.02 with Fisher exact test). Given the elevated death rate not related to the esophageal cancer and the median survival of 16 months, any potential benefit from this time-consuming procedure is debatable.

Axillary nodal involvement (ANI) remains an essential prognostic factor for breast cancer patients, as it implies the necessity of systemic adjuvant treatment and locoregional irradiation. Axillary dissection (AD) contributes to improved local disease control and may increase survival. However, AD results in a 10%-25% incidence of long-term side effects, particularly lymphedema. Moreover, many small primary lesions with low risk of ANI are now discovered by screening, and it is not clear whether AD should be used routinely in all such patients. Sentinel lymph node biopsy (SLNB) is a selective procedure that allows selective staging of the axilla with few side effects. However, indications for SLNB are not precisely defined yet, so some patients may be understaged and the axillary relapse rate may increase. This study was conducted to help clinicians assess the risk of ANI and analyzed six clinical and histological parameters to optimally recognize patients who might benefit from SLNB, with a minimal risk of false-negative rate. We retrospectively analyzed the ANI risk among 893 women treated by conservative surgery and radiation for T0, T1, or T2 invasive tumours < 3 cm in size. All patients underwent AD with sampling of a minimum of seven lymph nodes. In each case, we assessed the clinical and pathological tumor size, histological subtype (including grading), tumor location, age at diagnosis, and breast size. The global ANI rate in the entire cohort was 25.3%. In multivariate analysis, three variables were significantly predictive of the ANI risk: tumor size (P < 0.0001), histological subtype (P = 0.0005), and breast size (P = 0.004). By combining these parameters, we were able to define three categories of women with low (< 20%), intermediate (21%-25%), and high (> 25%) ANI risk. We suggest that women with nonpalpable (T0), T1 grade 1/2, and T2 < 3 cm tumors of medullary, mucinous, tubular, or papillary histological subtype are the best candidates for SLNB. For other patients with a higher ANI risk tumor, AD may still remain the best procedure to obtain accurate staging and definitive local control.

The aim of this study was to evaluate the reliability and accuracy of sentinel node biopsy for invasive breast cancer and the predictability of axillary node status. Between January 1996 and June 1997 a total of 73 patients underwent patent blue dye lymphatic mapping and sentinel node biopsy followed by standard (level I and II) axillary node dissection (one bilateral procedure). The sentinel node was identified in 82.4% (61/74) of the cases and was predictive of axillary status in 96.7% (59/61). The false-negative rate of the procedure was 8.0% (2/25). The sentinel node was involved in 37.7% (23/61) and was the only one invaded in 30.4% (7/23). The sensitivity of the procedure was 92% (CI95% 74-99%) and its specificity 100%. It is currently considered to be an attractive new procedure undergoing evaluation in prospective controlled trials. This study confirmed the reliability and reproducibility of intraoperative lymphatic mapping and sentinel node biopsy. This is the first step toward a new era of minimally invasive axillary surgery for breast cancer.

HSC70 interacting protein (HIP) is an essential cytoplasmic cochaperone involved in the regulation of HSC70 chaperone activity and the maturation of progesterone receptor. To determine the quaternary structure and the gross conformation of the protein in solution, a wide array of biochemical and biophysical techniques has been used. Size-exclusion chromatography and sedimentation velocity indicate the presence of a single species with a Stokes radius, R(s), of 55 A and a sedimentation coefficient, s degrees (20,w), of 4.34 S. The combination of these data gives a molecular mass of 101 000 Da, a value close to that of the theoretical molecular mass of a dimer (87 090 Da). Sedimentation equilibrium, performed at various protein concentrations and rotor speeds, gives a molecular mass of 88 284 Da, almost in exact agreement with the molecular mass of a dimer. On the basis of these data, a frictional ratio f/f(0) of 1.6 is obtained, suggesting an elongated shape for the HIP dimer. Secondary structure predictions, supported by circular dichroism experiments, indicate that HIP is an almost all alpha-protein, able to form extended coiled coils. Using threading and comparative model building methods, a structural model of a segment of HIP involved in HSC70 binding has been constructed and potential sites of interaction between HIP and HSC70 are proposed on the basis of electrostatic as well as shape complementarity. Altogether, these results indicate that HIP is an elongated dimer, able to bind two HSC70 molecules through its TPR regions, and suggest the existence of a versatile binding site on HSC70 that may be involved in the interaction of the chaperone with the cochaperones or other interacting proteins.

The human unr gene encodes an 85 kDa protein which contains five cold shock domains (CSD). The capacity of Unr to interact in vitro with RNA and its intracellular localization suggest that Unr could be involved in some aspect of cytoplasmic mRNA metabolism. As a step towards identification of Unr mRNA targets, we investigated the RNA-binding specificity of Unr by an in vitro selection approach (SELEX). Purine-rich sequences were selected by Unr, leading to the identification of two related consensus sequences characterized by a conserved core motif AAGUA/G or AACG downstream of a purine stretch. These consensus sequences are 11-14 nt long and appear unstructured. RNAs containing a consensus sequence were bound specifically by Unr with an apparent dissociation constant of 1 x 10(-8) M and both elements, the 5' purine stretch and the core motif, were shown to contribute to the high affinity. When the N-terminal and C-terminal CSD were analyzed individually, they exhibited a lower affinity than Unr for winner sequences (5- and 100-fold, respectively) but with similar binding specificity. Two combinations of CSDs, CSD1-2-3 and CSD1*2-3-4-5 were sufficient to achieve the high affinity of Unr, indicating some redundancy between the CSDs of Unr for RNA recognition. The SELEX-generated consensus motifs for Unr differ from the AACAUC motif selected by the Xenopus Y-box factor FRGY2, indicating that a diversity of RNA sequences could be recognized by CSD-containing proteins.

To evaluate the results, prognostic factors and especially side-effects of the treatment for subdiaphragmatic Hodgkin's disease (SHD) a retrospective study was conducted in the Haematology Departments and in the Cancer Centres of Nancy and Strasbourg between 1976 and 1990; 55 patients corresponding to the IA to IIB SHD stages were analysed. The median age was 45 years. In accordance with Ann Arbor classification, we observed 12 CS IA (21.3%), 2 CS IB (3.5%), 14 CS IIA (25.4%) and 27 CS IIB (49.7%). Twenty-five patients (45.4%) underwent laparotomy with spleen involvement in 10 cases. Fifteen patients (27.3%) had exclusive radiotherapy, 10 by inverted-Y field with or without splenic field, 5 by limited field to inguinal and homolateral iliac nodes. Forty patients had prior chemotherapy, 18 by MOPP protocol, 18 by hybrid MOPP/ABVD protocol and 4 by other schemes. The total dose delivered ranged from 26 to 45 Gy. With a median follow-up of 8 years, the overall and disease specific survival rates are respectively 61% and 83% at 10 years. Nine patients relapsed (16.4%), 4 among the 15 (26.6%) treated by exclusive irradiation and 5 among the 40 (12.5%) treated by combined therapy. We observed 8.3%, 21.4% and 18.5% of relapses respectively among the clinical stages IA, IIA and IIB. Eleven patients (20%) developed a second cancer. Twenty-six long-term complications were noted, nine of which concerned the digestive system. The only significant prognostic factor is age, with 10-year specific survival rates of 96% and 66% respectively for patients younger and older than 50 years (p=0.0003). Our data confirm that the most appropriate treatment for stage IA is exclusive radiotherapy and combined therapy for all other cases. With the use of CT-scan and eventually lymphography, the laparotomy is reserved only for cases with an uncertain diagnosis. Tobacco use is also clearly a risk factor in our series for late vascular complications and second cancers.

Objective: To analyze the effects on color vision of chronic exposure to mixtures of solvents including ethyl acetate, ethanol, and ketones among the workers of a large factory specializing in the manufacture of photoengraved aluminum packaging., Methods: We analyzed a group of 129 subjects who had been exposed to solvents for more than 3 years (mean age 40 years, range 25 59 years) and a nonexposed group of 120 subjects (mean age 41 years, range 21-57 years). The two groups had a similar length of service (17 and 19 years on average, respectively). The exposed subjects consumed more tobacco and alcohol than the nonexposed workers. The study involved administration of the Lanthony D-15 desaturated test. The subjects were classified as having or not having dyschromatopsia on the basis of Lanthony's criteria and the chromatic confusion index (CCI) was calculated according to Bowman's method. After observation of the work stations and analysis of an occupational questionnaire the findings were used to construct a cumulative exposure index covering the whole of each subject's working life. Air samples were taken at each work station and in each production sector to determine current exposure., Results: The average cumulative exposure index was 194 (median 174, range 27-513). The average hygienic effect index (according to ACGIH recommendations), regularly used for atmospheres containing mixtures of products, varied between 12% and 27% of the occupational limit values permitted under French legislation. As regards color vision, 23% of the exposed group had dyschromatopsia, as did 13% of the nonexposed group, with the odds ratio (OR) adjusted for age and consumption of tobacco and alcohol being 1.99 (1.02, 3.89). The analysis of the dose-response relationship according to the cumulative exposure index showed an OR of 1.59 for the lowly exposed group (index < 174) and an OR of 2.40 for the highly exposed group (index > 174) as compared with the nonexposed group. Subjects with complex color vision loss (n=23) had a significantly higher cumulative exposure index than those with blue-yellow loss (n=23; 232 versus 155; P=0.04). The CCI was on average higher in the exposed group, but the difference between the two groups was not significant., Conclusion: The results of this study are in favor of an increased risk for impairment of chromatic discrimination among workers exposed to mixtures of solvents including mainly ethyl acetate, ethanol, and ketones.

Aim of the Study: The goal of this study was to evaluate the technical feasibility of sentinel node biopsy in breast cancer and its predictivity of axillary node status., Patients and Methods: Between January 1996 and June 1997, 128 patients with invasive breast carcinomas, referred to the Cancer Center of Strasbourg and Lyon (France), underwent lymphatic mapping (Patent Blue dye) and sentinel node biopsy followed by axillary clearance (Berg's level I to II)., Results: Sentinel node was identified in 76.5% of cases and was predictive of axillary status in 94.9% of cases. The false negative rate of the procedure was 5.1%. Sentinel lymph node was involved in 43.9% of cases and it was the only one involved in 30.2% of cases. The sensitivity of the procedure was 94% (CI: 95% = [88%-98%]) and its specificity 100%., Conclusion: Actually considered as new attractive procedure under ongoing evaluation in prospective controlled trials, this study confirms the feasibility and reproductibility of lymphatic mapping and sentinel node biopsy, first stage before entering a new era of minimally invasive axillary surgery in breast cancer.

Study Aim: The aim of the study was to assess, by clinical and histological predictive factors, the axillary lymph-node involvement (pN+) in early breast cancers., Materials and Methods: Eight hundred ninety-three patients with unilateral invasive breast cancer were studied. The evaluated parameters included clinical size (T), pathological size (pT), histological subtype (ductal infiltrating, according to grading 1, 2, 3, lobular infiltrating and others), age (less than 40, 40 to 60 and above 60). Furthermore, a new parameter, the dosimetric breast size, recently described, was included (Eur J Cancer 1997; 33: 2432-4)., Results: The global rate of pN+ was 25.3%, with respectively, pN1: 10%, pN2-3: 8.4% and pN > 3: 6.9%. According to T, the pN+ rates were, respectively, 13.8%, 19.8% and 36.2% in the T0, T1 and T2 < or = 3 cm groups. According to pT, the pN+ rates were, respectively, 11.1%, 17.7%, 23.5%, 30.1% and 36% in the following groups: 0-9.9 mm, 10-14.9 mm, 15-19.9 mm, 20-24.9 mm and 25-29.9 mm. For the ductal infiltrating carcinoma, according to the gradings 1, 2 and 3, we found, respectively, 18.3%, 27.2% and 37.8% of pN+. For the lobular infiltrating carcinoma and the other histological subtypes, the rates were 22.7% and 10%, respectively. For the three age categories cited above the pN+ rates were, respectively, 30.3%, 25.8% and 22.4%. According to breast size we found 30.1% and 24.4% of pN+ respectively for small and medium or large dosimetric breast size. After a multivariate analysis, three factors were significant for pN+ risk: clinical tumor size (P = 0.0001), histological subtype (P = 0.0005) and dosimetric breast size (P = 0.004). With a combination of these three factors, the pN+ rates varied from 5% to 50%., Conclusions: The authors conclude that both clinical and pathological characteristics of the primary tumor (specified by previous core biopsy) can indicate the risk for axillary node metastases, and allow selection of candidates for limited axilla surgery (sentinel node).

A study of 50 patients with hyperthyroidism was conducted to evaluate the effect of preoperative administration of Lugol's iodine solution on thyroid blood flow. Highly significant reductions in diameter, time-averaged velocity, and volume flow of the superior thyroid artery were demonstrated after administration of Lugol's solution. The Duplex ultrasound scanning used in this study is a noninvasive, inexpensive, accurate, and reproducible technique suitable for analysis of thyroid blood flow in hyperthyroidism. On the basis of current ultrasonographic results and low postoperative morbidity in patients, Lugol's solution is well tolerated and may be recommended for use before thyroidectomy, especially for diffuse toxic goiters and Graves disease.

In a retrospective multicentric analysis, 63 women treated between 1941 to 1988 for Hodgkin's disease (HD) subsequently developed 76 breast cancers (BC). The median age at diagnosis of HD was 26 years (range 7-67), and 22 women (35%) were 20 years old or less. Exclusive radiotherapy (RT) was used in 36 women (57%) and combined modalities with chemotherapy (CT) in 25 (39%). Breast cancer occurred after a median interval of 16 years (range 2-40) and the median age at diagnosis of the first BC was 42 years (range 25-73). TNM classification (UICC, 1978) showed 10 T0 (non-palpable lesions) (13%), 20 T1 (26%), 22 T2 (29%), 8 T3 (11%), 7 T4 (9%) and 9 Tx (12%), giving altogether a total of 76 tumours, including, respectively, 5 and 8 bilateral synchronous and metachronous lesions. Among the 68 tumours initially discovered, 53 ductal infiltrating, one lobular infiltrating and two medullary carcinomas were found. Moreover, two fibrosarcomas and 10 ductal carcinoma in situ (DCIS) were also found. Among 50 axillary dissections for invasive carcinomas, histological involvement was found in 31 cases (62%). 45 tumours were treated by mastectomy, without (n = 35) or with (n = 10) RT. 27 tumours had lumpectomy, without (n = 7) or with RT (n = 20). 2 others received RT only, and one only CT. 7 patients (11%) developed isolated local recurrence. 20 patients (32%) developed metastases and all died; 38 are in complete remission, whereas 5 died of intercurrent disease. The 5-year disease-specific survival rate by the Kaplan-Meier method was 61%. The 5-year disease-specific survival rate for pN0, pN1-3 and pN > or = 3 groups were 91%, 66% and 0%, respectively (P < 0.0001) and 100%, 88%, 64% and 23% for the T0, T1, T2 and T3T4 groups, respectively. These secondary BCs seem to be of two types: a large number of aggressive tumours with a very unfavourable prognosis (especially in the case of pN > 3 and/or T3T4); and many tumours with a 'slow development' such as DCIS and microinvasive lesions, especially in patients treated exclusively by RT. Moreover, a very unusual rate of bilateral tumours (21%) was observed. These secondary BC could be 'in field', in 'border of field' or 'out of field'. However, a complete analysis of doses delivered by supradiaphragmatic irradiation was often very difficult, due to large variations in several parameters. We conclude that young women and girls treated for HD should be carefully monitored by clinical examination, mammography and ultrasonography.

To evaluate the risk of local recurrence following breast-conserving therapy for breast cancer, we measured the distance between each entry point of the irradiation on the surface of the breast in line with the axis of the external and internal tangential fields (dosimetric breast size). 652 breast cancer patients were retrospectively analysed, with a median age of 51 years and a median follow-up of 99 months (range 84-192). There were 50 local recurrences, 44 isolated and 6 associated with nodal recurrence or metastases. The global rates of local recurrences at 5 and 10 years were 5.3% and 9%, respectively (Kaplan-Meier analysis). Following a Cox's multivariate analysis, the only significant and independent parameters related to local recurrence were quality of excision, age at diagnosis and dosimetric breast size. For a small dosimetric breast size (< or = 10 cm), the rate of local recurrence was 14.1 compared with 11.8 for medium dosimetric breast size (> 10 cm-< or = 12 cm) and 5.2 for large dosimetric breast size (> 12 cm). If the analysis was restricted to only those with complete excision, then the relative risk for a patient with a small dosimetric breast size was three times that for a large breast size.

This study was performed on 282 patients with primary head and neck squamous cell carcinomas to evaluate the prognostic importance of 11q13 amplification. Amplification of the 11q13 DNA markers, HST-1/FGF-4 and BCL-1, evaluated by Southern and slot blot hybridisation, was detected in 52% of tumours. 11q13 amplification was associated with tumour site since this alteration occurred in 76% of tumours arising in the hypopharynx, versus 40% in the other sites (P = 0.0007). 11q13 amplification was also significantly related to the presence of involved neck lymph nodes (P = 0.013). The relationship between 11q13 amplification and risk of progression was studied in two subgroups of head and neck cancer patients with regard to treatment modalities. The presence of 11q13 amplification in the tumour was not significantly associated with a shorter event-free survival (P = 0.82) and crude survival (P = 0.61) of the 201 patients treated by surgery and postoperative radiotherapy. Similarly, absence of a relationship was observed for the group of 79 patients treated by surgery alone. These results confirm that 11q13 amplification is a prominent event in head and neck squamous cell carcinoma, indicating that it may be a common genetic event in the development of these neoplasms, but is not a reliable prognostic marker.

From 1970 to 1992, 31 pure ductal carcinoma in situ (DCIS) of the male breast treated in 19 French Regional Cancer Centres were reviewed. They represent 5% of all breast cancers treated in men in the same period. The median age was 58 years, but 6 patients were younger than 40 years. TNM classification (UICC, 1978) showed 12 T0 (discovered only by bloody nipple discharge), 10 T1, 5 T2 and four unclassified tumours (Tx). 11 patients (35.5%) had clinical gynecomastia, and three (10%) had a family history of breast cancer. 6 patients underwent lumpectomy, and 25 mastectomy. Axillary dissection was performed in 19 cases. 6 cases received postoperative irradiation. 15 out of 31 lesions were of the papillary subtype, pure or associated with a cribriform component. The size of the 12 measured lesions varied from 3 to 45 mm. All lymph nodes sampled were negative. With a median follow-up of 83 months, 4 patients (13%) presented a local relapse (LR), respectively, at 12, 27, 36 and 55 months. 3 of these patients had been initially treated by lumpectomy. In one case LR was still in situ, but already infiltrating in the 3 others. Radical salvage surgery was performed in 3 cases, but one patient developed metastases and died 30 months later. The last patient was treated by multiple local excisions and tamoxifen. One 43-year-old patient developed a contralateral DCIS and three others developed a metachronous cancer. The aetiology and risk factors of male breast cancer remain unknown. Gynecomastia, which implies an imbalance between androgen and oestrogen, may be a predisposing factor. As in women, DCIS in the male breast has a good prognosis. Total mastectomy without axillary dissection is the basic treatment. Frequently, the first symptom is a bloody nipple discharge. The age of occurrence is younger than for infiltrating carcinoma, suggesting that DCIS is the first step in the development of breast cancer.

Clinical outcome of gut's stromal tumors is difficult to predict by morphological data. The prognostic significance of a set of morphological criterias and immunostaining for proliferating cell nuclear antigen (PCNA) was studied. Thirty six tumours were classified benign (group A) or malignant (group B) according to ten year follow-up. Patient's sex and age, site of origin, tumour size, mitotic count and cytonuclear atypia were considered. Growth kinetic was studied by immunohistochemical analysis of PCNA (PC 10, DakoR). In univariate analysis, mitotic count, PCNA index, tumor size and cytonuclear atypia were associated with patient outcome. However, in multivariate analysis, only mitotic count and tumour size were independent prognosis factors. Thus, mitotic count remains the best prognostic indicator for these tumours since a cut off value of 2 mitosis/high power field allows an accurate prognosis in 33/36 tumors.

From 1960 to 1986, 397 cases of non-metastatic male breast cancer (MBC) treated in 14 French regional cancer centres were reviewed. The median age was 64 years (range 25-93). TNM classification (UICC, 1978) showed seven T0, 79 T1, 162 T2, 31 T3, 74 T4 and 44 unclassified tumours (Tx). Clinical positive lymph nodes were found in 31% of the patients. 24 patients received radiotherapy only, and 373 underwent surgery, 247 of these with postoperative irradiation. Adjuvant chemotherapy and hormonal therapy were used in 71 and 68 patients, respectively. There were 382 infiltrating carcinomas and 15 pure ductal carcinoma in situ. Lymph node involvement was found in 56% of infiltrating carcinoma. The oestrogen (ER) and progesterone (PgR) receptors were positive in 79% and 77%, respectively, of examined cases. Isolated local and regional recurrence were observed in 8.8% and 4.5% of cases, respectively and 40% of patients developed metastases. The crude survival rates by Kaplan-Meier method were 65% and 38% at 5 and 10 years, respectively, and the disease-specific survival rates (without death due to intercurrent disease or second cancer) was 74% at 5 years and 51% at 10 years. The disease-specific survival rate for pN- and pN+ groups were 77% and 39% at 10 years. The prognostic factors were clinical size (T) and histological axillary status (pN-/pN+). The relative risk of death for pN- was 1.0, 2.0 and 3.2 in the T0-T1, T2 and T3-T4 groups, respectively. For pN+, these relative risks increased 1.9, 3.9 and 6.0 in the same groups. The optimal treatment include modified radical mastectomy and irradiation for cases with risk factors of local relapse (nodal invasion, large tumour with cutaneous or muscular involvement). Locoregional failure had unfavourable prognosis. First-line adjuvant treatment seems to be tamoxifen, due to the very high rate of positive hormonal receptors and the old age of the patients, which contraindicate chemotherapy in many cases. The prognosis of patients with breast cancer is the same in male and female patients when disease-specific survival rate, tumour size and axillary involvement are compared.

It is still unknown what if any relationships exist between intake of macronutrients by the elderly, and their functional or cognitive handicaps, particularly for free living elderly people. We investigated 226 men and 215 women, aged 65 or more, free living and in good health. They were randomly selected in the département of Bas-Rhin, after stratification for age, sex and residence (rural or urban). Handicaps and cognitive functions of each subject were assessed with the Géronte scale and the Mini-Mental State Examination (MMSE), respectively. Food intake was measured by a three-day record. A multiple correspondence analysis concluded that functional parameters and macronutrient intakes were rather independent. The relationships found were detailed by a backward stepwise logistic regression. In men, alcohol intake was associated with an improvement in functional and cognitive parameters, and polyunsaturated fatty acids with the capacity to move outside the home. In women, lipid intake increased the MMSE score. Overweight in women was linked with better functional and cognitive performances, and in men with the capacity to move outside the home. In both sexes, age worsened the score of functional and cognitive parameters. In conclusion, macronutrient intakes and functional or cognitive parameters were found to be mutually independent; this suggests that macronutrient deficiencies are of little importance in the worsening functional or mental autonomy of the elderly. The relationships found between functional variables and alcohol or polyunsaturated fatty acid intakes in men, and lipid intakes in women, and overweight in both sexes might evidence a better state of health.

Tamoxifen is the anti-estrogen the most widely used in breast cancer. The duration of its prescription, as adjuvant treatment, tends to increase (5 years, and even more) and now it is used in chemoprevention. A slight increase of thromboembolic complications was noted in some studies. This article evaluates the frequency of thromboembolic accidents (TEA) in 441 postmenopausal patients treated by an association of conservative radiosurgery, tamoxifen +/- chemotherapy, for a breast carcinoma T0, T1T2 < 4 cm. Nineteen patients (4.3%), all in remission, presented a TEA, between 1 and 44 months after the beginning of the tamoxifen treatment. We observed seven pulmonary embolisms (PE), 11 deep venous thromboses (DVT) and an acute arterial ischemia. Two patients aged 74 and 80 years died, the others had a favourable evolution under anticoagulant treatment. Among these 19 patients, six presented known risks factors (phlebitis, cardiovascular disorders) and ten had a "favouring circumstance" aggravating the risk of TEA (surgical operation, severe infection, fracture). Their median age was 65 years (61 for all the 441 patients). We noted eight cases of breast lobular cancer (42%) among these 19 patients (11% for all the patients). Among postmenopausal patients, the indication of tamoxifen must be evaluated according to the benefits expected in those with high risk factors of TEA (history of heart failure, obesity, spread varix, age > 65 years). In case of DVT and/or PE, this treatment seems contra-indicated. In case of "favouring circumstances", a hypocoagulant or systematic anticoagulant treatment must be proposed. In case of combined chemotherapy, it is better to start tamoxifen at the end of the treatment. These simple prophylactic measures should allow to reduce significantly the risk of TEA in postmenopausal patients with adjuvant anti-estrogenotherapy.

The L-myc DNA restriction fragment length polymorphism (RFLF), revealed by EcoRI digestion, has been evaluated in a case-control study including 161 head and neck cancer (HNSCC) patients and 160 normal healthy individuals with similar smoking and alcohol habits. No significant difference in the distribution of L-myc genotypes (LL, LS or SS) was found between the two populations implying thus no predisposition to head and neck tumour by either allele. There was no significant association between L-myc genotypes and the usual clinicopathological features such as T staging, differentiation status and lymph node involvement. Moreover, follow-up data from 154 patients was obtained and correlated with the L-myc pattern. No significant difference was observed in metastasis occurrence, multiple cancer incidence and survival data in the patients classified according to the L-myc genotypes; only a trend to preferentially develop metastasis in lung for patients with S allele was noted. In conclusion, our data shows that the L-myc typing does not contribute to HNSCC risk or prognosis assessment. A review of L-myc RFLP published studies shows contradictory results even on the same type of tumour and emphasizes the lacunae in understanding the biological role of L-myc for valid interpretation of L-myc allelic associations with cancer susceptibility or prognosis.

Objectives: With effective screening programmes, the global incidence of in situ ductal carcinoma of the breast has risen to 15%, representing 20 to 30% of the mammographically detected T0 tumours. Prognosis is generally good in these tumours, but treatment has in the past, paradoxically, relied on extensive surgery. We report our experience with conservative radiosurgery performed in such cases from 1980 to 1990., Methods: There were 86 patients with a mean age of 52 years. Initial TNM classification was T0 = 57, T1 = 17, T2 = 9 and Tx = 3. All underwent limited surgery (quadrantectomy: 17; lumpectomy: 69) and 49 had axillary dissection. All received breast irradiation with scar boost (46-50 Gy + 10-14 Gy with classical fractionation). Thirty one postmenopausal women received adjuvant tamoxifen. The quality of the resection was good in 77 cases, doubtful or incomplete in 9. In one case axillary nodal involvement was found. The histological subtype was clearly identified in 63 cases. With a median follow-up of 58 months, 3 local relapses occurred (3.4%), at 27, 48 and 52 months respectively. One was in situ and two invasive. All were clinical lesions (2 T1 and 1 T2); two had incomplete or doubtful excision and all received less than 60 Gy on the tumour bed. All had mastectomy. Two are alive and well but one developed multiple metastasis. Five other women had subsequent surgery for suspicion of local relapse but all had benign disease. One developed contralateral disease 20 months later. Two women died subsequently due to a second cancer., Conclusion: These results confirm the importance of the excision quality and suggests a possible dose-effect in the control of in situ ductal carcinoma by radiotherapy. The recent results of the B-17 NSBAP trial also conclude that the radiosurgical conservative treatment, for limited in situ ductal carcinoma, is a reasonable alternative to mastectomy.

Of 441 postmenopausal breast cancer patients who received adjuvant tamoxifen, 19 had thromboembolic accidents (4.3%). All were in remission when thrombosis occurred. One patient died of bilateral pulmonary embolism. In the other cases, thromboembolic disorders were found to be reversible after the withdrawal of tamoxifen and anticoagulant treatment. Some patients had a history of vascular disorders, and others required prolonged bed rest which may have contributed as an aggravating circumstance to thrombotic events. Our study suggests that thromboembolic risk factors as well as potential vascular disorders induced by aggravating conditions have to be carefully examined in postmenopausal patients treated by adjuvant tamoxifen therapy. This is especially true in women with lobular breast cancer and aged more than 60 years.

Gradual tumor tissue devascularization during mastectomy is thought to decrease estrogen (ER) and progesterone (PgR) receptor activity. To determine whether or not hormone receptor values could be influenced by different mastectomy techniques, 62 patients with carcinoma of the breast had a Tru-cut needle (Baxter Healthcare Corporation) biopsy (premastectomy sample) and underwent modified radical mastectomy (postmastectomy sample) either before (group 1, 40 patients) or after (group 2, 22 patients) axillary lymph node dissection. When the two surgical procedures were compared in 33 patients in whom it could be assessed, no significant tendency (p = 0.51 for ER and p = 0.36 for PgR) for the postmastectomy sample to have hormone receptors levels less than samples taken at biopsy was detected. Overall, in the two groups (44 assessable patients), comparison with respect of each patient, between premastectomy and postmastectomy samples showed that the variations in either ER or PgR receptor values, determined by immunoenzymatic assays, were not statistically significant (p = 0.32 for ER and p = 0.21 for PgR). The current results indicated the relative stability of steroid receptors during the two modified radical mastectomy procedures and suggested that a systematic reference determination of hormone receptors on biopsy before modified radical mastectomy is unnecessary.

Background: The objectives of this study were to demonstrate the usefulness of Receiver Operating Characteristic (ROC) analysis in the definition of a positive threshold in the comparison of two in vitro tests for detecting IgE antibodies and to determine the clinical relevance of specific IgE tests according to the sensitivity and specificity determined by ROC analysis., Methods: Specific IgE levels were compared with the use of both MATRIX (Abbott Laboratories, Chicago, Ill.) and PHADEZYM (Pharmacia, Uppsala, Sweden) tests in 109 patients: 86 allergic patients and 23 control subjects. All allergic patients had a clinical history of allergy to mite, cat, grass pollen, or birch pollen and positive skin prick test results to the suspected allergen. Using various levels of specific IgE, we determined the points of the ROC curves with the best ratio of true positives to false positives for four aeroallergens (i.e., mite, cat, grass pollen, and birch pollen)., Results: Except for mite allergen there was no correspondence between the positive threshold values determined by ROC analysis with MATRIX and PHADEZYM tests. In terms of class, when ROC analysis was used, the threshold was class III with the MATRIX test and class II with PHADEZYM test for cat, grass pollen, and birch pollen and class III for mite. According to the threshold value, sensitivity and specificity for MATRIX and PHADEZYM tests were similar except for cat, for which the PHADEZYM test had a lower sensitivity (0.71) than the MATRIX test (0.90). With mite allergen the predictive value of only one positive MATRIX test result was 0.96. The specificities of MATRIX and PHADEZYM tests were 100% in both nonatopic and atopic control groups., Conclusions: We conclude that ROC analysis is a reliable method for comparing IgE in vitro tests and that it emphasizes the lack of correspondence between arbitrary units given for each in vitro test. ROC analysis appears to be a good method for helping to standardize IgE in vitro tests.

Therapeutic drug monitoring of 5-FU was investigated in patients with head and neck cancer treated with cisplatin (100 mg/m2) followed by 5-day continuous infusion of 5-FU (1 g/m2/d). In a first step, the 5-FU pharmacokinetic and pharmacodynamic analysis of 25 cycles for 14 patients revealed that both the time-concentration product (ASC) for the entire cycle and the half-cycle were predictive of cycle toxicity and a dose adjustment diagram was established. In a second experiment, this diagram was used for treatment monitoring in a group of 35 patients (97 cycles). The clinical toxicity and response were compared with those of a retrospective group of 55 patients (184 cycles) treated with the same protocol without dose adjustment. Pharmacokinetic follow-up of 5-FU has proved to be an objective means to significantly reduce haematological and/or digestive tract toxicity (47 to 33%). Moreover, although dose reduction was often performed, the clinical response was not affected (42-44%), neither was the median survival time (8.8 months-14.1 months in control and adapted groups respectively).

In a retrospective and multicentre study 106 cases treated from 1970 to 1985 were analysed. The patients' median age was 64 years. TNM classification showed 20 T1, 48 T2, 2 T3, 32 T4 and 4 Tx. Twenty one patients had clinical gynaecomastia; 99 underwent surgery and 85 radiotherapy; 32 received adjuvant chemotherapy or hormonal therapy. The main histological type was ductal infiltrating carcinoma; 82 axillary dissections were performed, and positive lymph nodes were found in 67 percent of the cases. Hormone receptors were positive in 15 out of 20 measured cases. Five and 10 years overall survival rates (Kaplan-Meier) were 57 and 37 percent, and corrected survival rates 68 and 55 percent respectively. The main prognostic factor remains the clinical size of the tumour (T) and histologically axillary node status (pN). Eleven patients developed a second metachronous cancer. The aetiology of male breast cancer is a poorly known as that of female breast cancer. Nevertheless, imbalance among oestrogens and androgens due to metabolic, infectious or pharmacological causes is probably responsible, at least in part, for this cancer. An on-going multicentre prospective national trial tries to address this question.

The extent of the biosynthesis of selenoproteins in mitochondria and cytosol of Saccharomyces uvarum depends on the sodium selenite concentration in the medium. In mitochondria there is a selenoprotein (SP 1) exhibiting glutathione peroxidase activity whose concentration already reaches a maximum at low concentrations of sodium selenite. A second selenoprotein (SP 2) was found in mitochondria and cytosol. Both proteins contain L-selenocysteine. The molecular masses of SP 1 and SP 2 are 73,000 Da and 83,000 Da, respectively. A subunit of SP 1 was found to have a molecular mass of 30,000 Da. SP 2, identified as a glycoprotein, has subunits with molecular masses of 36,500 Da and 5,000 Da. The selenium concentration of the total yeast increases from 260 micrograms/kg dry weight to 280 mg/kg dry weight after supplementation of the medium with sodium selenite.

Male breast cancer represents about only 1% of all breast cancers. We have analysed a retrospective, multicentric series of 404 patients, initially non-metastatic, with mean age of 63 years. The 5 and 10-year overall survival rates were 65 and 36% respectively. Sixty-eight patients developed secondary cancer. From ten patients who already presented with cancer (2.5%) 3 cases corresponded to prostatic cancer treated by estrogen. Four had synchronous cancer (1%). Three and eight patients respectively had a synchronous and metachronous contralateral breast cancer (2.7% of bilateral cancer). Forty-three other patients (10.6%) developed metachronous cancer. The main tumor types were: prostate (9), lung (6), colon and rectum (6), esophagus (4). Four patients developed various hematologic malignancies and 14 patients, various types of solid tumors. From these 43 patients, 27 died; 19 as a result of secondary cancer. This represents 9% of all deaths among the 404 patients. While the bilateral cancer rate is similar to women, the second cancer rate appears to be higher in men. From hematological malignancies, chemotherapy and radiotherapy do not seem to contribute to this high incidence of second cancer.