Clinical pathways in the management of the obese: Pre- and postoperative aspects.

INTRODUCTION: Bariatric surgery (BS) leads to substantial weight loss accompanied by reversal of several obesity-related co-morbidities and reduced mortality. However, surgery is associated with risks and its nearly irreversible characteristic requires a clearly established pre- and postoperative clinical pathway. In France, this pathway relies on recommendations made by the High Authority of Health (Haute Autorité de santé (HAS)) in 2009; an update is awaited in 2023. PREOPERATIVE ASPECTS: BS should be proposed only after failure of well-conducted medical treatment and is intended for patients whose body mass index (BMI) is ≥40kg/m2 or for those with BMI ≥35kg/m2 who also have co-morbidities amenable to improvement, and in whom there are no contra-indications, particularly, those related to general anesthesia or psychological factors. The success and safety of surgical management requires preparation of the patient with regard to dietetic and nutritional counseling, and physical activity. The possibility of complications must be recognized and communicated, including, in view of the large variability of outcomes between individuals, the risk of failure and regain of weight. POSTOPERATIVE ASPECTS: Prior to the operation, patients should be informed of and accept the program of postoperative clinical and laboratory follow-up, as well as the need for lifelong supplementation in micronutrients and the financial implications including what patients may have to pay out of their own pocket. CONCLUSION: Surgical management of obesity cannot replace the multidisciplinary medical management of severe obesity. The results obtained by BS are sustainable only if the patient adheres to the proposed modalities. New drugs such a GLP-1 analogues have opened encouraging perspectives as possible alternatives to BS in certain indications.

[Towards better management for sexual offenders: Presentation and conclusions of a public hearing concerning prevention, assessment, and care]. / Audition publique auteurs de violences sexuelles : prévention, évaluation, prise en charge des 14 et 15 juin 2018 : perspectives et préconisations.

In France, since the law of June 17, 1998, sexual offenders may be convicted to ambulatory mandatory care, articulated with the justice. Twenty years after the implementation of this law, while social and technological developments have redefined certain aspects of delinquency, reference documents and practice guidelines remain to be updated. This is why the professionals of the main structures and associations dealing with perpetrators of sexual violence organized a public hearing under the sponsorship of the French Federation of Resource Centers for Sexual Violence Perpetrators (FFCRIAVS) according to the methodology and with the accompaniment of the High Authority of Health. This article presents the global methodology of the public hearing "Sexual Offenders: Prevention, Evaluation and Care" which was conducted on June 14 and 15, 2018. Thirty-three experts replied to27 questions and presented their conclusions to an Audition Committee and an audience of 200 persons representative of the civil and professional society. After a public debate, the hearing committee prepared a report in which they proposed propositions in order to better care for sexual offenders.

Fostering infant food texture acceptance: A pilot intervention promoting food texture introduction between 8 and 15 months.

Healthy infant feeding practices form the basis of healthy eating behaviour later in life. The effect of providing parents with recommendations on textured food introduction between 8 and 15 months on children's experience with and acceptance of textured foods was studied. Sixty parent/child dyads were randomly assigned to a control group (CG) receiving current French recommendations and an intervention group (IG) receiving a brochure with supplementary advice, tips and monthly counselling on food texture introduction. After the intervention, parents completed self-report measures about the introduction of 188 food items, including purees, soft/small pieces, hard/large pieces and double textures. Children's acceptance of eight textured foods was assessed in a laboratory setting. Parents in the IG introduced more soft/small food pieces (P = 0.004) but not more complex textures (P = 0.15). There was no group difference in children acceptance for any of the textured foods offered in the laboratory. Independent of their study group, children's exposure to texture was associated with birth order, self-feeding with fingers, low gagging frequency and seldom use of commercial baby foods. Higher acceptance was associated with higher exposure to food pieces but not to pureed foods (either smooth or rough) and with children's eating behavioural traits (high food enjoyment, high food responsiveness and low food fussiness). This pilot intervention demonstrated that providing information can be effective in promoting the introduction of small and soft food pieces, but the most effective way to influence the introduction of more challenging textures (hard pieces and double texture) is uncertain. Further research should focus on the identification of barriers to complex texture introduction and on how building on this knowledge for a population-based public health intervention.

Fatty acids: a role for Africa?

Health effects of fatty acids have been very controversial. Total mortality is inversely associated with the amount of total fat consumed. In contrast, trans fatty acids or SFA intake is positively related to mortality while the inverse is observed with consumption of MUFA or PUFA. Among PUFA, long-chain (LC) n-3 PUFA have many beneficial effects. Dietary intake of some types of fatty acids is specific to Africa. Energy from saturated fat does not exceed 14% and energy from n-6 PUFA does not exceed 8% of total energy intake. Dietary intake of LC n-3 PUFA is less than 100 mg/d whereas international recommendations promote 250-500 mg/d. Consumption of plant n-3 PUFA mainly α-linolenic acid (ALA) is highly variable depending on the country. Both fish and ALA availability are low in several African countries. The prevalence of diabetes and cardiovascular events remain very low in Africa, partly explained by the fact that the whole dietary pattern is globally the best of all continents. One objective of 'fat for Africa' could be to increase, as much as possible, the dietary intake of LC n-3 PUFA by promoting sustainable aquaculture and to maintain as much as possible traditional dietary pattern by preventing a tendency to westernisation, provided that the amount of energy and protein is sufficient to fight against wasting and stunting where it still exists.

Identifying the ideal profile of French yogurts for different clusters of consumers.

Identifying the sensory properties that affect consumer preferences for food products is an important feature of product development. Different methods, such as external preference mapping or partial least squares regression, are used to establish relationships between sensory data and consumer preferences and to identify sensory attributes that drive consumer preferences, by highlighting optimum products. Plain French yogurts were evaluated by a sensory profiling method performed by 12 trained judges. In parallel, 180 consumers were asked to score their overall liking and complete a cognitive restraint questionnaire. After hierarchical cluster analysis on the liking scores, preference mapping using a quadratic regression model was performed. Five clusters of consumers were identified as a function of different preference patterns. Contrary to our expectations, fat levels were not discriminating. For each cluster, the results of preference mapping enabled the identification of optimum products. A comparison of the 5 sensory profiles revealed numerous differences between key sensory attributes. For example, one consumer cluster had a strong preference for products perceived as very thick, grainy, but with a less flowing texture, less sticky, whey presence and color, in contrast to other clusters. In addition, each segment of consumers was characterized according to the results of the cognitive restraint questionnaire.

Fish oil prevents the adrenal activation elicited by mental stress in healthy men.

OBJECTIVES: A diet rich in n-3 fatty acids (fish oils) is associated with reduced risks of cardiovascular and metabolic diseases, but the mechanisms remain incompletely understood. Sympathoadrenal activation is postulated to be involved in the pathogenesis of these diseases, and may be inhibited by n-3 fatty acids. We therefore evaluated the effects of a diet supplemented with n-3 fatty acids on the stimulation of the sympathetic nervous system and of stress hormones elicited by a mental stress. METHODS: Seven human volunteers were studied on two occasions, before and after 3 weeks of supplementation with 7.2 g/day fish oil. On each occasion, the concentrations of plasma cortisol, and catecholamines, energy expenditure (indirect calorimetry), and adipose tissue lipolysis (plasma non esterified fatty acid concentrations) were monitored in basal conditions followed by a 30 min mental stress (mental arithmetics and Stroop's test) and a 30 min recovery period. RESULTS: In control conditions, mental stress significantly increased heart rate, mean blood pressure, and energy expenditure. It increased plasma epinephrine from 60.9 +/- 6.2 to 89.3 +/- 16.1 pg/ml (p<0.05), plasma cortisol from 291 +/- 32 to 372 +/- 37 micromol/l (p<0.05) and plasma non esterified fatty acids from 409 +/- 113 to 544 +/- 89 micromol/l (p<0.05). After 3 weeks of a diet supplemented with n-3 fatty acids, the stimulation by mental stress of plasma epinephrine, cortisol, energy expenditure, and plasma non esterified fatty acids concentrations, were all significantly blunted. CONCLUSION: Supplementation with n-3 fatty acids inhibits the adrenal activation elicited by a mental stress, presumably through effects exerted at the level of the central nervous system.

Acute metabolic effects of dialysis fluids during CAPD.

Because the osmotic agents currently used for peritoneal dialysis, ie, glucose or amino acids, are also substrates, a metabolic transfer occurs during their peritoneal absorption. After the delivery of a 3.86% glucose dialysis solution, about 100% of the glucose absorbed through the peritoneal is oxidized. So, this glucose contributes fully to the energy load of the patients. Peritoneal glucose delivery also entertains hyperglycaemia and hyperinsulinaemia as compared to oral glucose. When compared to healthy subjects, oral glucose in continuous ambulatory peritoneal dialysis (CAPD) patients induces a higher glycaemic and insulinaemic response. This traduces insulin resistance in CAPD patients even after months of that renal replacement therapy. When amino acids are used in place of glucose in dialysis solution, they stimulate whole body protein turnover and are used mainly for protein synthesis. When a meal is coingested, protein breakdown is inhibited which reinforces the positive effect of the solution on protein balance.

[Cardiac abnormalities in a prospective series of 40 patients with type 2 diabetes]. / Anomalies cardiaques d'une série prospective de 40 patients diabétiques de type 2.

Cardiovascular mortality, the principal cause of early death in diabetics, is multifactorial. A prospective study was undertaken to analyse the different factors of excess cardiac complications in 40 patients with type 2 diabetes, whatever the symptomatology, by making an inventory of the cardiac abnormalities (systolic and diastolic left ventricular function, left ventricular hypertrophy, abnormalities of myocardial perfusion, heart rate variability and arrhythmias). Patients underwent 24 hour Holter monitoring, high amplification signal averaged electrocardiography, echocardiography, Thallium scintigraphy with a dipyridamole test followed by coronary angiography when positive. Patients were aged 60 +/- 8 years, diabetics for 11.8 +/- 6.8 years, and had associated cardiovascular risk factors: 85% were obese, 75% were hypertensive, 62.5% had hypercholesterolaemia and 60% were smokers. The HbA1C was 9.2 +/- 19%. An increased left ventricular mass was observed in 34.2% of patients. The left ventricular ejection fraction was normal (59.1 +/- 6.8%); 69.7% of patients had left ventricular diastolic dysfunction. Reduced heart rate variability was observed in 51.8% of cases. Late ventricular potentials were recorded on high amplification signal averaging in 39.5% of patients; 25.6% had significant ventricular extrasystoles and 52.2% had atrial extrasystoles. Twelve patients (45%) underwent Thallium myocardial scintigraphy with a positive dipyridamole test, 8 of whom had coronary lesions on angiography. The excess cardiac complications of diabetes is mainly due to ischaemic heart disease aggravated by autonomic neuropathy, left ventricular diastolic dysfunction, arrhythmias and left ventricular hypertrophy. In future, larger series are required to demonstrate that this detection can guide therapeutic intervention and reduce cardiac morbidity and mortality of diabetics.

Study of interaction phenomena between aroma compounds and carbohydrate matrixes by inverse gas chromatography.

Besides the conventional techniques used for the investigation of food-flavor interactions, inverse gas chromatography (IGC) may provide a useful tool for the direct assessment of the retention of aroma compounds in a matrix. IGC consists of single reference compound injections at a fixed temperature onto a column which stationary phase is the material of interest. We have applied this technique to high amylose corn starch, wheat starch, and beta-cyclodextrin matrixes, using aroma compounds presenting various functional groups. Low energy interactions were measured which may result from polar or hydrophobic binding. Starch behaved under these conditions as a polar chromatographic phase. We also focused on the influence of a physical modification of the starch on its retention properties toward 3,7-dimethyl-2,6-octadien-1-al. Retention was found to be greater after a specific thermal treatment. As checked by DSC (differential scanning calorimetry) and DMTA (dynamic mechanical and thermal analysis), the observed changes are believed to be related to the glass transition of the starch. For the time being, the dehydration of the matrix associated with the lack of control of the relative humidity within the column is the main restriction to this technique.

Effects of an amino acid dialysate on leucine metabolism in continuous ambulatory peritoneal dialysis patients.

BACKGROUND: Protein-energy malnutrition is frequent in continuous ambulatory peritoneal dialysis (CAPD) patients. The use of amino acids in the dialysate could improve the protein balance, especially if associated to a concomitant energy intake. METHODS: A 1.1% amino acid solution for peritoneal dialysis was administered to CAPD patients over 30 minutes during concomitant absorption of 600 ml water (control study) or of a 600 kcal meal/600 ml. Leucine metabolism was studied using the combination of intravenous [2H3] and intraperitoneal [13C] leucine. RESULTS: The rate of leucine appearance was stimulated by 56 and 53% (control and meal) at 45 minutes. The rates of leucine appearance and disappearance were lower from 180 to 300 minutes during the meal versus control study (P < 0.05). Proteolysis was unaffected during the control study and was inhibited by 25% during the meal study (P < 0.05). During the five-hour cycle dialysis with or without a meal, 80% of the leucine administered into the peritoneum was absorbed. Forty-one percent was retained in the splanchnic bed. Forty-three percent was used for protein synthesis, and 16% was oxidized. CONCLUSIONS: This amino acids solution is efficaciously utilized for protein synthesis in CAPD patients with no effect on protein breakdown. The concomitant ingestion of a carbohydrate-lipid meal inhibits protein breakdown and reinforces a positive effect of the amino acids solution on protein balance.

Effects of oral glucose on intermediary metabolism in continuous ambulatory peritoneal dialysis patients versus healthy subjects.

OBJECTIVE: To explore the mechanisms and metabolic consequences of the insulin resistance of patients treated by continuous ambulatory peritoneal dialysis (CAPD). DESIGN: CAPD patients and healthy subjects ingested a similar mean oral glucose load per kilogram of fat-free mass (FFM) [1.20+/-0.03 g/(kg FFM) vs 1.20+/-0.06 g/(kg FFM); CAPD vs healthy subjects]. Substrate oxidation was monitored over 6 hours using indirect calorimetry. SETTING: Peritoneal dialysis unit of a tertiary-care institutional center. OUTCOME MEASURES: Glycemia, insulinemia, substrate oxidation. PATIENTS: Six CAPD patients (68+/-5 yr) and 6 healthy subjects (24+/-1 yr). The CAPD patients had similar body mass index (21.4+/-1.3 vs 22.9+/-1.1 kg/m2), a higher percent fat (25.8%+/-3.7% vs 16%+/-2.2%; p < 0.05), and a lower FFM (42.2+/-2.2 kg vs 56.5+/-2.6 kg; p < 0.01) than healthy subjects. RESULTS: The CAPD patients displayed a higher glycemic and insulinemic responses to glucose than did healthy subjects (p < 0.05), but similar glucose oxidation and storage. Lipid oxidation and plasma nonesterified fatty acids were not increased in CAPD patients versus healthy subjects, in spite of a higher adiposity. Fat oxidation was related to fat mass in CAPD patients (r2 = 0.77, p < 0.05) but not in healthy subjects (r2 = 0.05). CONCLUSION: CAPD patients display an insulin-resistance not explained by an increased lipid oxidation. The maintenance of intracellular glucose utilization at the expense of higher glycemic and insulinemic responses suggests a defective glucose transport.

[Long-term prognostic role of steroid receptors in cancer of the breast]. / Rôle pronostique à long terme des récepteurs stéroïdiens dans le cancer du sein.

We screened for the prognostic value of estrogen receptor (ER) and progesterone receptor (PR) through a multicentric study of 2,257 operable breast cancer patients who did not received adjuvant therapy. Three hundred and seven local-regional recurrences, 105 metachronous contralateral breast cancer, 589 metastases and 537 deaths from cancer had been diagnosed with a median follow-up of 8.5 years. A total of 69% of the tumors were ER positive and 54% PR positive. For statistical analysis, 1,665 patients were studied because of complete clinical and biological data. In univariate analysis, ER and PR status were of prognostic value for the metastases-free interval (MFI) and the overall survival (OS). In multivariate analysis (Cox proportional hazard model), only the ER status showed a significant difference between positive and negative groups regarding the MFI and OS. By using Cox regression model with time-dependent covariates, we show that the predictive value of ER status of the primary tumor decreases by approximately 20% per year, losing its significance after 8 years of follow-up. These results show that ER and PR status have a relatively limited predictive value and their major interest remain in the domain of therapeutic decision.

Quantitative determination of c-erbB-2 in human breast tumours: potential prognostic significance of low values.

The purpose of this prospective multicentric study was to quantify the c-erbB-2 protein and investigate its relationship with DNA amplification and with various prognostic parameters of breast cancer. A total of 1062 primary operable human breast tumours were collected from six French anticancer centres. The c-erbB-2 protein was measured using an enzymoimmunoassay using two monoclonal antibodies directed against the extracellular domain of the protein. The results were expressed in arbitrary units/mg membrane protein (AU) after adjustment for the anticancer centre. A significant association was found between the dosage of the protein and DNA amplification (P = 0.0001). A value of 200 AU was found to maximise sensibility and specificity and was chosen as a cut-off for over-expression. Significant associations were found between c-erbB-2 values and oestrogen receptor (ER) (P = 0.01), progesterone receptor (PgR) (P = 0.0001) and histological grading (P = 0.01). The extreme high values (above the mean plus one standard deviation, S.D.) were significantly more numerous in ER- (P = 10(-16)), PgR- (P = 10(-14)) and grade III (P = 10(-8)) tumours. The extreme low values (below the mean minus one S.D.) were significantly more numerous in ER- (P = 10(-9)) and PgR- (P = 0.02) tumours. This prospective study confirms that high c-erbB-2 protein values are linked to poor prognostic factors and shows for the first time that low values are also linked to hormone receptor negative tumours, suggesting that these low values might also have a negative prognostic significance.

Long-term supplementation of culture medium with essential fatty acids alters alpha-linolenic acid uptake in Caco-2 clone TC7.

We investigated the influence of four different culture media: 20% fetal bovine serum (FBS), 5% FBS, 5% FBS supplemented with 10 mg x L(-1) linoleic acid (18:2(n-6)) or alpha-linolenic acid (18:3(n-3)) on alpha-linolenic acid apical uptake in clone TC7 of human intestinal Caco-2 cell line. Neither cellular viability nor cell monolayer integrity and permeability were altered by the four culture conditions. Our results show that the different culture media led to changes in alpha-linolenic acid maximal rate of uptake (Vmax) but did not alter the apparent transport constant (Km). Reducing FBS concentration from 20% to 5% increased significantly the rate of alpha-linolenic acid uptake, which was further increased by supplementation of the medium with 18:2(n-6) or 18:3(n-3). Supplementation with essential fatty acids led to a marked enrichment of brush-border membrane phospholipids in polyunsaturated fatty acids of the corresponding series and decreased significantly the levels of monounsaturated fatty acids. Saturated fatty acids, unsaturation index, and cholesterol/fatty acid ratios were unchanged. No clear relation could be established between the changes in membrane lipid composition and the alterations of alpha-linolenic acid uptake. These results indicate a weak influence of membrane lipid composition in the modulation of the uptake. Therefore, the increase of uptake following long-term supplementation of TC7 cells with essential fatty acids could be attributed to an increase of the expression of membrane protein(s) involved in the apical uptake of long-chain fatty acids. This remains to be established.

Effects of adrenergic blockade on hepatic glucose production during ethanol administration.

Acute ethanol administration stimulates sympathetic nervous system activity. The present study was designed to determine whether this sympathetic activation affects glycogenolysis and total hepatic glucose production (HGP) during ethanol-induced inhibition of gluconeogenesis. Nineteen volunteers participated in four protocols. Two protocols aimed to study--using combined infusion of [6,6-2H2]glucose and [U-13C]glucose, VCO2 and 13CO2 measurements--the effects of ethanol infusion alone (n = 10) or with propranolol (n = 6) or phentolamine infusion (n = 4) on HGP, glucose disposal (Rd), glucose oxidation [13C]Glcox and non-oxidative glucose disposal (NOGD = Rd - [13C]Glcox). The fourth protocol assessed the effects of saline infusion alone on HGP. Using ethanol, HGP decreased by 23%, Rd by 20% and glycaemia by 9% (all P < 0.001); heart rate increased by 10%, whereas blood pressure remained unchanged. The effects were not observed with saline, except a slight (10%) decrease in HGP (P < 0.01 vs. ethanol). Ethanol did not affect [13C]Glcox but decreased NOGD by 73% (P < 0.001). Propranolol or phentolamine did not alter any of the effects of ethanol on glucose metabolism, but decreased mean arterial pressure. Propranolol prevented the ethanol-induced increase in heart rate. In conclusion, ethanol decreased blood glucose by decreasing HGP, presumably by inhibiting gluconeogenesis. Sympathetic activation prevented the decrease in blood pressure produced by ethanol but did not stimulate glycogenolysis.

Effects of dexamethasone on hepatic glucose production and fructose metabolism in healthy humans.

This study was designed to determine whether glucocorticoids alter autoregulation of glucose production and fructose metabolism. Two protocols with either dexamethasone (DEX) or placebo (Placebo) were performed in six healthy men during hourly ingestion of[13C]fructose (1.33 mmol.kg-1.h-1) for 3 h. In both protocols, endogenous glucose production (EGP) increased by 8 (Placebo) and 7% (DEX) after fructose, whereas gluconeogenesis from fructose represented 82 (Placebo) and 72% (DEX) of EGP. Fructose oxidation measured from breath 13CO2 was similar in both protocols [9.3 +/- 0.7 (Placebo) and 9.6 +/- 0.5 mumol.kg-1.min-1 (DEX)]. Nonoxidative carbohydrate disposal, calculated as fructose administration rate minus net carbohydrate oxidation rate after fructose ingestion measured by indirect calorimetry, was also similar in both protocols [5.8 +/- 0.8 (Placebo) and 5.9 +/- 2.0 mumol.kg-1.min-1 (DEX)]. We concluded that dexamethasone 1) does not alter the autoregulatory process that prevents a fructose-induced increase in gluconeogenesis from increasing total glucose production and 2) does not affect oxidative and nonoxidative pathways of fructose. This indicates that the insulin-regulated enzymes involved in these pathways are not affected in a major way by dexamethasone.

Effect of dietary fish oil on body fat mass and basal fat oxidation in healthy adults.

OBJECTIVE: To investigate whether the substitution of fish oil for visible fats in a control diet (52% carbohydrates, 16% protein, 32% fat; P:S 0.2) influences body fat mass and substrate oxidation in healthy adults. DESIGN: Six volunteers (5 men; 23 +/- 2 y; BMI: 21.9 +/- 1.6) were fed a control diet (C) ad libitum during a period of three weeks and, 10-12 weeks later, the same diet where 6 g/d of visible fat were replaced by 6 g/d of fish oil (FO) for another three weeks. RESULTS: Energy intakes (IKA-calorimeter) were unchanged. Body fat mass (Dual-energy X-ray absorptiometry) decreased with FO (-0.88 +/- 0.16 vs -0.3 +/- 0.34 kg; FO vs C; P < 0.05). When adjusted for lean body mass (Ancova), resting metabolic rate (indirect calorimetry) was unchanged. Basal respiratory quotient decreased with FO (0.815 +/- 0.02 vs 0.834 +/- 0.02; P < 0.05) and basal lipid oxidation increased with FO (1.06 +/- 0.17 vs 0.87 +/- 0.13 mg kg(-1) min(-1); P < 0.05). CONCLUSION: Dietary FO reduces body fat mass and stimulates lipid oxidation in healthy adults.

Mechanisms and kinetics of alpha-linolenic acid uptake in Caco-2 clone TC7.

The uptake kinetics of alpha-linolenic acid (18:3(n - 3)), an essential fatty acid, were investigated in the human intestinal cell line Caco-2. Four clones (PD10, PF11, PD7 and TC7) from the heterogeneous parental Caco-2 cells population were used. After a screening step using isolated cells, the TC7 clone was selected for the study of alpha-linolenic acid uptake. [1-(14)C]linolenic acid dissolved in 10 mM taurocholate was presented to the microvillus plasma membrane (apical side) of TC7 differentiated cells, grown on a semi-permeable polycarbonate membrane. The results show that the initial rate of uptake is not a linear function of the 18:3(n- 3) monomer concentration in the incubation medium. In the monomer concentration range studied (0.2 to 36 microM) apical uptake was saturable and followed Michaelis-Menten kinetics (V(max) = 15.4 +/- 0.6 nmol/mg protein per min, K(m) = 14.3 +/- 1.3 microM). In addition, it was temperature- and energy-dependent but was apparently unaffected by the sodium gradient and intracellular metabolic fate of 18:3(n - 3). Excess of unlabeled saturated or unsaturated long chain fatty acids (C16 to C22) led to a 27-68% reduction of [1-(14)C]linolenic acid uptake. Likewise basolateral uptake was saturable (V(max) = 4.9 +/- 0.7 nmol/mg protein per min, K(m) = 8.7 +/- 2.9 microM). These facts argue in favour of the existence in these human intestinal cells of a carrier-mediated transport system for alpha-linolenic acid and probably other long chain fatty acids as well.

Prognostic value of steroid receptors after long-term follow-up of 2257 operable breast cancers.

The prognostic value of oestrogen receptor (ER) and progesterone receptor (PR) was estimated through a multicentric study of 2257 operable breast cancer patients followed up for a median of 8.5 years. None of the patients had received adjuvant therapy. The series included 33.3% stage I patients, 57.1% stage II, 5.7% stage IIIa and 2.4% stage IIIb. At the end point of the study 589 metastases and 537 deaths from cancer were recorded. Receptor measurements were performed by radiolgand assay according to a uniform protocol. A total of 68.8% of the tumous were ER positive and 54.0% PR positive ( > or = 10 fmol mg-1 cytosol protein). In univariate analysis, ER and PR status (positive/negative) were of prognostic value (P < 0.001) for the disease-free interval (DFI), the metastases-free interval (MFI) and the overall survival (OS). The OS of the patients after a first metastasis was also significantly different between ER-positive and -negative tumours (P < 0.001). In multivariate analysis (Cox proportional hazard model, 1665 patients), only the ER status showed a significant difference (P < 0.01) between positive and negative groups regarding the DFI, MFI and OS. By using Cox non-proportional, time-dependent models, we show that the predictive value of ER status of the primary tumour decreases by approximately 20% per year, losing its significance after 8 years of follow-up. Overall, when compared with TNM and histological grading, ER and PR status have a low prognostic value, their major interest remaining solely in the domain of therapeutic decision.