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Biomedical subjects

P Maisonneuve

Publications and source records attributed to P Maisonneuve.

At least 91 records · Page 5Linked to original sources
PubMed1999

p21WAF1/CIP1 expression in colorectal carcinoma correlates with advanced disease stage and p53 mutations.

Defects in the mechanisms controlling the cell cycle are crucial in cell transformation and/or tumour progression. p21WAF1/CIP1 is an inhibitor of cyclin-dependent kinases, induced by p53-dependent and p53-independent pathways, which can block progression through the cell cycle. p21WAF1/CIP1 expression has been investigated immunohistochemically in a series of 191 patients with colorectal cancer of known p53 status. The purpose of the study was two-fold: to assess the relationship between p21WAF1/CIP1 immunoreactivity and p53 alterations, and to evaluate the prognostic significance of p21WAF1/CIP1 expression. In 96 carcinomas (51 per cent), p21WAF1/CIP1 was expressed in over 10 per cent of tumour cells, whereas in 26, p21WAF1/CIP1 was detected in under 10 per cent of neoplastic cells; 69 tumours lacked p21WAF1/CIP1 expression. Immunoreactivity was more frequent in tumours of the right colon (p < 0.003) and was inversely correlated with tumour stage (p < 0.03), p53 gene mutations (p < 0.0007), p53 protein accumulation (p < 0.019), and Bcl-2 expression (p < 0.0005). In univariate analysis, down-regulation of p21WAF1/CIP1 expression was associated with poor overall (p = 0.0022) and disease-free survival (p = 0.0009). Multivariate analysis, however, did not confirm any independent prognostic significance of p21WAF1/CIP1 expression. The results indicate that p21WAF1/CIP1 is associated with abnormal accumulation of p53 protein and the occurrence of p53 gene mutations in colorectal cancer and that lack of p21WAF1/CIP1 expression is correlated with reduced patient survival in univariate analysis. These data underline the crucial pathogenetic role of the p53-p21WAF1/CIP1 pathway in carcinomas of the large bowel.

Adenocarcinoma↗
PubMed1999

Chronic pancreatitis and other risk factors for pancreatic cancer.

Pancreatic cancer is the fourth or fifth most common form of cancer in Western countries. Early diagnosis is difficult and the overall mortality rate is high. Individuals at high risk for pancreatic cancer include smokers, African-Americans, and persons with various types of pancreatitis. As with other cancers, dietary factors play an important role. Approximately 10% of all pancreatic tumors may be related to an inherited germ line disorder.

Age of Onset↗
PubMed1999

Racial factors and the risk of chronic pancreatitis.

OBJECTIVE: It is unclear why some alcohol abusers develop alcoholic cirrhosis whereas others contract chronic pancreatitis. The aim of this study was to examine the importance of race as a risk factor for the development of chronic pancreatitis. METHODS: We compared the racial status of 1883 patients discharged with a first-listed diagnosis of two diseases strongly related to alcohol abuse: 433 patients with chronic pancreatitis (ICD 5771) and 1450 patients with alcoholic cirrhosis (ICD 5712). Information came from discharge statistics maintained by two acute care hospitals in New York City and one acute care hospital in Lisbon, Portugal. The study period included the years 1989-1996 in the US and 1989-1994 in Portugal. RESULTS: A total of 215 (50%) of the 433 chronic pancreatitis patients were black compared with 333 (23%) of the 1450 patients with alcoholic cirrhosis. When adjusted for sex and hospital site, patients with pancreatitis were significantly more likely to be black than patients with cirrhosis (odds ratio 2.5, 95% confidence interval 1.9-3.2, p < 0.001). CONCLUSIONS: In comparison with white patients, black patients are two to three times more likely to be hospitalized for chronic pancreatitis than alcoholic cirrhosis. This highly significant (p < 0.001) difference was observed in both men and women: in three different hospitals, and in two different countries. The explanation is unknown, but could be related to racial differences in diet, type or quantity of alcohol consumption, smoking, or ability to detoxify substances harmful to the liver or pancreas.

Adult↗
PubMed1999

Prognostic value of estrogen receptor status can be improved by combined evaluation of p53, Bcl2 and PgR expression: an immunohistochemical study on breast carcinoma with long-term follow-up.

Steroid receptor analysis is the only widely accepted prognostic/predictive marker in breast cancer (BC) treatment. In the present study we evaluated the prognostic role of ER/PgR with p53 and Bcl2, in a series of 277 BC (153 pN1/2, 122 pNO, 2 pNx) with a long-term follow-up (67 months for DFS, 75 months for OS). Our results, besides confirming the usefulness of ER immunohistochemical expression as a prognostic marker, showed that PgR expression alone had a borderline/not significant prognostic value in the whole series (p=0.08 for DFS and p=0.09 for OS), while showed to be prognostic in N+ cases (p=0.02 for DFS and p=0.03 for OS). PgR prognostic value, however, was not independent at the multivariate analysis. By combining ER with PgR, p53 and Bcl2, we showed that ER/p53 and ER/Bcl2 phenotypes had a better discriminant role than ER/PgR phenotype. The ER+/p53+ phenotype was at higher risk of relapse/death as compared with ER+/p53- phenotype. Conversely ER-/p53+ phenotype showed the most unfavourable prognosis. Similar results could be observed concerning ER/Bcl2 phenotypes. Our study showed that the combined evaluation of ER/PgR weakly enhanced the prognostic/predictive power of ER status alone. On the contrary, the combined evaluation of ER/p53 and ER/Bcl2, improved this prognostic/predictive capability and allowed the separation of ER positive and ER negative cases into subgroups with different prognosis.

Breast Neoplasms↗
PubMed1999

Pancreatico-biliary malignancy: prevalence and risk factors.

Tumors arising in the pancreatico-biliary system arise from the same embryological source and share several similar clinical features. For both sites, the mortality rate is high and early diagnosis is difficult. Despite these similarities, there are clear epidemiologic differences between cancers of the biliary tract and cancers of the pancreas. Gallbladder cancer is more frequent in females, whereas pancreatic cancer is more frequent in males. High-risk populations for gallbladder cancer include Native American Indians and Hispanic Americans. Black populations are at high risk for pancreatic cancer. Gallstones are causally related to gallbladder cancer, but for pancreatic cancer, smoking is the major known risk factor. The increasing frequency of cholecystectomy in persons with gallstones should result in a reduction in the incidence of gallbladder cancer. For pancreatic cancer, public health efforts to reduce smoking offers the best chance for prevention.

Biliary Tract Neoplasms↗
PubMed1998

Prevention of breast cancer with tamoxifen: preliminary findings from the Italian randomised trial among hysterectomised women. Italian Tamoxifen Prevention Study.

BACKGROUND: Tamoxifen is a candidate chemopreventive agent in breast cancer, although the drug may be associated with the development of endometrial cancer. Therefore we did a trial in hysterectomised women of tamoxifen as a chemopreventive. METHODS: In October, 1992, we started a double-blind placebo-controlled, randomised trial of tamoxifen in women (mainly in Italy) who did not have breast cancer and who had had a hysterectomy. Women were randomised to receive tamoxifen 20 mg per day or placebo, both orally for 5 years. The original plan was to follow the intervention phase by 5 years' follow-up. In June, 1997, the trialists and the data-monitoring committee decided to end recruitment primarily because of the number of women dropping out of the study. Recruitment ended on July 11, 1997, and the study will continue as planned. The primary endpoints are the occurrence of and deaths from breast cancer. This preliminary interim analysis is based on intention-to-treat. FINDINGS: 5408 women were randomised; participating women have a median follow-up of 46 months for major endpoints. 41 cases of breast cancer occurred so far; there have been no deaths from breast cancer. There is no difference in breast-cancer frequency between the placebo (22 cases) and tamoxifen (19) arms. There is a statistically significant reduction of breast cancer among women receiving tamoxifen who also used hormone-replacement therapy during the trial: among 390 women on such therapy and allocated to placebo, we found eight cases of breast cancer compared with one case among 362 women allocated to tamoxifen. Compared with the placebo group, there was a significantly increased risk of vascular events and hypertriglyceridaemia among women on tamoxifen. INTERPRETATION: Although this preliminary analysis has low power, in this cohort of women at low-to-normal risk of breast cancer, the postulated protective effects of tamoxifen are not yet apparent. Women using hormone-replacement therapy appear to have benefited from use of tamoxifen. There were no deaths from breast cancer recorded in women in the study. It is essential to continue follow-up to quantify the long-term risks and benefits of tamoxifen therapy.

Adult↗
PubMed1998

Incidence of hepatitis C in patients receiving different preparations of hepatitis B immunoglobulins after liver transplantation.

BACKGROUND: Recurrence of hepatitis B virus (HBV) or hepatitis C virus (HCV) infection after liver transplantation is a clinical problem. Polyclonal immunoglobulins against hepatitis B surface antigen (HBIGs) prevent the recurrence of HBV infection, but no effective prophylaxis is available for HCV infection. Before screening of blood donors was introduced in France, HBIGs may have contained antibody to HCV (anti-HCV). OBJECTIVE: To determine the influence of HBIG on the occurrence of hepatitis C after liver transplantation before and after 1990. DESIGN: Retrospective cohort study. SETTING: Liver transplantation unit of a university hospital. PATIENTS: 428 consecutive patients who had liver transplantation because of cirrhosis between 1984 and 1994. MEASUREMENTS: Detection of serum HCV RNA before and 1 year after transplantation and findings on liver graft biopsy. RESULTS: Among the 218 patients who had HCV infection before transplantation, the incidence of HCV viremia after transplantation was lower in those receiving HBIG than in those not receiving HBIG (25 of 46 patients [54%] compared with 162 of 172 patients [94%]; P < 0.001). In patients receiving HBIG, the incidence of HCV viremia after transplantation was lower among those who had transplantation before March 1990 than among those who had transplantation after this date (15 of 33 patients [45%] compared with 10 of 13 patients [77%]; P = 0.05). Among the 210 patients without HCV infection before transplantation, acquired infection was significantly less frequent in those receiving HBIG than in those not receiving HBIG (18 of 68 patients [26%] compared with 40 of 86 patients [47%]; P < 0.001). Passively transmitted anti-HCV was transiently detected in patients receiving HBIG before March 1990. Multivariate analysis in patients with HCV infection before transplantation showed that the absence of HBIG and transplantation after March 1990 were independent significant risk factors for chronic hepatitis C after transplantation. CONCLUSIONS: Polyclonal immunoglobulins that are treated for viral decontamination and contain anti-HCV could prevent HCV infection.

Adult↗
PubMed1998

Mortality after the treatment of hyperthyroidism with radioactive iodine.

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

Cardiovascular Diseases↗
PubMed1998

Prognostic implications of epidermal growth factor receptor immunoreactivity in squamous cell carcinoma of the oral mucosa.

To evaluate the clinical significance of the expression of epidermal growth factor receptor (EGFr) in oral squamous cell carcinoma (SCC), 100 formalin-fixed, paraffin-embedded cases of this tumour and ten samples of normal oral mucosa were immunostained with a monoclonal anti-EGFr antibody using an immunoalkaline phosphatase (APAAP) technique. EGFr immunoreactivity was detected in 36 of 100 tumours and in all samples of normal mucosa. Tumour cells demonstrated distinct membrane staining in 14 cases and predominantly cytoplasmic staining in 22 additional cases. EGFr was exclusively localized on the cell membrane of normal epithelial cells. Kaplan-Meyer survival curves and Cox proportional hazard regression models were used to assess overall survival and disease-free survival. A significant positive correlation was shown between EGFr membranous immunoreactivity and prolonged survival, in both univariate and multivariate analyses. Accordingly, patients with oral SCC showing down-regulated expression of membranous EGFr, who are more likely to suffer recurrence and death, should be strictly followed up and possibly treated with more aggressive therapeutic regimens.

Adult↗
PubMed1998

Effect of tamoxifen and transdermal hormone replacement therapy on cardiovascular risk factors in a prevention trial. Italian Chemoprevention Group.

The combination of tamoxifen and transdermal hormone replacement therapy (HRT) may potentially reduce risks and side-effects of either agent, but an adverse interaction could attenuate their beneficial effects. We assessed the effects of their combination on cardiovascular risk factors within a prevention trial of tamoxifen. Baseline and 12-month measurements of total, low-density lipoprotein (LDL)- and high-density lipoprotein (HDL)-cholesterol, platelets and white blood cells were obtained in the following four groups: tamoxifen (n = 1117), placebo (n = 1112), tamoxifen and HRT (n = 68), placebo and HRT (n = 87). The analysis was further extended to women who were on HRT at randomization but discontinued it during the 12-month intervention period (n = 33 on tamoxifen and n = 35 on placebo) and to women who were not on HRT but started it during intervention (n = 36 in both arms of the study). Compared with small changes in the placebo group, tamoxifen was associated with changes in total, LDL- and HDL-cholesterol of approximately -9%, -19% and +0.2% in continuous HRT users compared with -9%, -14% and -0.8% in never HRT users. Similarly, there was no interaction on platelet count. In contrast, the decrease in total and LDL-cholesterol levels induced by tamoxifen was blunted by two-thirds in women who started HRT while on tamoxifen (P = 0.051 for the interaction term). We conclude that the beneficial effects of tamoxifen on cardiovascular risk factors are unchanged in current HRT users, whereas they may be attenuated in women who start transdermal HRT while on tamoxifen. Whereas a trial of tamoxifen in women already on transdermal HRT is warranted, prescription of HRT during tamoxifen may attenuate its activity.

Breast Neoplasms↗
PubMed1998

Epidemiology of sociodemographic characteristics, lifestyle, medical history, and colon cancer: a case-control study among French Canadians in Montreal.

Colon cancer is the second most common cancer in both men and women in North America and other developed countries. In a population-based case-control study of colon cancer among French Canadians in greater Montreal, a total of 402 cases and 668 controls were interviewed. The cancer cases were identified through the admission offices of five major Francophone teaching hospitals in Montreal from 1989 to 1993. The controls, matched by age, sex, place of residence, and language, were selected by a modified random digit dialing method. The results show that subjects who had ever been married had a lower risk for colon cancer (odds ratio [OR]: 0.58; 95% confidence interval [95% CI]: 0.48-0.84) than did individuals who had never been married. A significant association (OR: 1.90; p for trend = 0.003) was found between the height of subjects and the risk of colon cancer. The OR for individuals with a family history of colorectal cancer was 2.78 with a p value of 0.01. A direct and significant association (OR: 2.01) was found among constipation, use of laxatives (OR: 1.41), and the risk of colon cancer. Among women, a suggestive inverse association was detected between the number of full-term pregnancies and the risk of colon cancer in female subjects (the OR for five or more pregnancies was 0.58 with a p for trend of 0.08). There was also a suggestive linear trend (increased age-decreased risk) between age at menarche and the risk of colon cancer. No association was apparent between other sociodemographic characteristics and the risk of colon cancer. In conclusion, married individuals had lower risk for colon cancer, perhaps due to food habits or other characteristics of being single. Higher height and weight history 10 years before the diagnosis of cancer are risk factors for breast cancer, while both current weight and body mass index seem to be protective. Positive family history of colon cancer increased the risk of colon cancer significantly.

Adult↗
PubMed1998

Sociodemographic characteristics, smoking, medical and family history, and breast cancer.

The relationship between sociodemographic characteristics, lifestyle, family history of cancer, medical history, and reproductive factors and breast cancer was investigated in a population-based case-control study of French Canadians in Montreal. In this study, a total of 414 French-Canadian cases and 429 age- and language-matched population controls were interviewed. Ever-married women showed significantly lower risk (OR: 0.64 [0.45-0.92]) for breast cancer, as did smokers (OR: 0.73 [0.55-0.98]), particularly of nonfilter cigarettes (OR: 0.36 [0.17-0.72]). Weight history, both for the year before the diagnosis of breast cancer and 10 years previously, was associated with risk for the disease. A strong inverse relationship was found between the number of full-term pregnancies (OR: 0.48 [0.28-0.82]) and the risk of breast cancer, while the p trend for late age at first pregnancy (p = 0.02) and menopause (p = 0.004) was statistically significant. A history of breast problems (OR: 1.87 [1.34-2.60]) and a history of breast cancer in relatives (OR: 2.95 [1.63-5.34]) were strongly associated with risk. This study confirms the risk factors of late age at first full-term pregnancy, nulliparity, late age at menopause, and positive family history of breast cancer in the etiology of this disease. Perhaps the protective effect of smoking against breast cancer could be due to its antiestrogenic influence.

Adult↗
PubMed1998

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

Carcinogens present in cigarette smoke and diet have been associated with pancreatic cancer. We hypothesized that heterocyclic and aromatic amines implicated in these exposures could be involved as causative agents and that therefore genetic variation in enzymes metabolizing these carcinogens could modify the risk of developing malignant and benign pancreatic disease. The effect of the genetic polymorphism of acetyltransferases (NAT1) and NAT2), glutathione S-transferase M1 (GSTM1) and NAD(P)H: quinone oxidoreductase 1 (NQO1) on the risk of pancreatic diseases (cancer, pancreatitis) was examined in a case-control study. PCR-based assays were used for genotype analysis of genomic DNA from whole blood cells. Samples collected from Caucasian patients with diagnosed pancreatic cancer (n = 81), with non-alcoholic (n = 41) and alcoholic pancreatitis (n = 73) and from asymptomatic control subjects (n = 78) were analysed. The prevalence of GSTM1 null genotype and of NAT2 fast and slow acetylator genotypes and the distribution of frequencies for NQO1 genotypes did not differ in subjects with pancreatic diseases vs controls. For NAT1 slow acetylators a non-significant excess (P = 0.18) was found among pancreatic cancer cases vs controls. There was a significant over-representation of the GSTM1 AB or B genotype in all pancreatic disease cases combined (OR = 2.6; P < 0.05). When concurrent controls were pooled with literature controls (n = 1427), OR was 1.4 (P = 0.08). The results of this study, requiring confirmation, suggest that the polymorphism of GSTM1 and NAT1 enzymes may be associated with a modest increase in susceptibility to pancreatic diseases.

Acetyltransferases↗