A prospective cohort study on dietary fat and the risk of postmenopausal breast cancer.

In 1986 a prospective cohort study on diet and cancer was started in the Netherlands among 62,573 women ages 55-69 years. Baseline information on diet and other risk factors was collected with a questionnaire. Cancer incidence was measured by record linkage with cancer registries and a pathology register. A case-cohort approach was used, in which the accumulated person time in the cohort was estimated by follow-up of a randomly selected subcohort (n = 1812). After 3.3 years of follow-up, 471 incident breast cancer cases were available for analysis. Questionnaire data for these cases and the 1716 female subcohort members without a history of cancer other than skin cancer were analyzed. In a multivariate analysis, controlling for traditional risk factors, the relative rates for breast cancer in increasing quintiles of energy-adjusted total fat intake were 1.00, 1.00, 1.34, 1.22, 1.08 (P-trend, 0.32). For saturated fat there was some evidence for a weak positive association when quintiles were used (relative rates in quintiles 1-5, 1.00, 1.22, 1.22, 1.38, 1.39; P-trend, 0.049). The 95% confidence interval (CI) for the top quintile was 0.94-2.06, however; and when saturated fat was used as a continuous variable, the effect was no longer significant (P = 0.20). Relative rate estimates for the highest versus lowest quintiles of monounsaturated fat, polyunsaturated fat, and cholesterol intake were 0.75 (95% CI, 0.50-1.12), 0.95 (95% CI, 0.64-1.40) and 1.09 (95% CI, 0.74-1.61), respectively, with no evidence for significant trends. This prospective study does not support a major role of dietary fat in the etiology of postmenopausal breast cancer.

Examination of bone marrow biopsy specimens and staging of small cell lung cancer.

Bone marrow biopsy specimens were evaluated retrospectively in 63 of 88 (72%) patients with small cell lung cancer (SCLC). Significant differences were not found between extensive disease (ED) patients with or without bone marrow metastases in survival nor in nadirs of leucocytes or platelets subsequent to chemotherapy. A panel of antibodies was used to investigate whether immunohistochemical analysis on routinely processed bone marrow biopsy specimens could detect marrow metastases more effectively than conventional microscopy. In histologically proven marrow metastases and in control SCLC sections a combination of an antibody against cytokeratin 8, 18 and 19 (NCL5D3) and an antibody against neurone specific enolase was validated for detection of metastases. In histologically negative marrow biopsy samples, however, this combination did not yield any additional tumour positive cases. Therefore, histological evaluation of a bone marrow biopsy specimen, even when analysed by immunohistochemistry, does not contribute information relevant for staging, therapy evaluation or prognosis in SCLC.

Inflammatory bowel disease: is there any relation between smoking status and disease presentation? European Collaborative IBD Study Group.

Smoking is associated with Crohn's disease and nonsmoking with ulcerative colitis. The aim of this study was to compare the clinical features at diagnosis and during the first year of follow-up in smokers and nonsmokers with inflammatory bowel disease (IBD). In 19 centers across Europe, a prospective study was performed of 457 newly diagnosed patients with Crohn's disease and 930 with ulcerative colitis. The characteristics of the disease were recorded by the treating physician by using a standard protocol at the time of diagnosis. Treatment characteristics were assessed after 1 year of follow-up. Weight loss occurred significantly more often in smoking patients with Crohn's disease, as well as in smokers with ulcerative colitis (p < 0.02), and diarrhea was more frequent in smoking patients with Crohn's disease compared with non-smoking individuals (p < 0.01). Patients with Crohn's disease who smoke were less likely to have colonic involvement (p < 0.01) and were more often prescribed immunosuppressive medication (p < 0.02). The study suggests that (a) smoking protects the colon from inflammation and (b) is associated with more active disease in Crohn's disease. The association between weight loss and smoking in both diseases is probably due to a general effect of smoking. The reported relation between smoking and the course of Crohn's disease is a strong argument for encouraging patients to give up smoking.

The role of histopathologic subtyping in predicting neurologic complications in small-cell lung-cancer.

We examined the significance of histologic subtyping of small cell lung cancer (SCLC) as a prognostic factor for neurologic complications and in particular central nervous system (CNS) metastases. Pretreatment material of 239 consecutive patients with SCLC was retrospectively reexamined according to the histologic subclassification of the Pathology Panel of the International Association for the Study of Lung Cancer. Besides the classic small cell type (n=178), this subclassification distinguishes two variant cell types: mixed (n=31) and combined (n=1), which were treated as one group in the further statistical analysis. Twenty nine cases were not classified, for the following reasons: autopsy material only (n=14), slides missing (n=7), and initial SCLC diagnosis changed (n=8). The results showed that neurologic complications registered in a prospective neurologic follow-up were common in both subtypes and predominantly metastatic in nature. The data did not reveal any significant difference between histologic subtypes with regard to CNS metastases and brain metastatic-free survival. Paraneoplastic syndromes tended to occur more frequently in patients with classic small cell type. However, this relationship needs further study. It was concluded that no prognostic relevance exists for histologic subtyping with respect to neurologic complications.

Haematologic parameters as risk factors for cardiac infarction, in an occupational health care setting.

It is still controversial, whether moderately high haematocrit (Ht) and haemoglobin (Hb) values are risk factors for coronary heart disease. Using the computerized data-system of the Periodical Medical Examination (PME) of Phillips' International Electrical Company, a case-control study was carried out. Cases were male workers (n = 104, from 50 to 60 years of age) who had suffered a first, non-fatal myocardial infarction, and who had had a PME prior (on the average 16 months) to the occurrence of infarction. For each case two age-matched healthy controls were selected from the PME-attendancy list (= 208). For each subject information was abstracted from the PME-records about haematologic parameters and covariates (smoking, cholesterol, blood pressure, pulse-rate, weight, height, FEV5, consumption of antihypertensive agents). After dichotomizing the haematocrit and haemoglobin values at their whole sample means (0.46 l/l and 9.7 mmol/l respectively) in "low" (lower than or equal to the mean) and "high" (greater than the mean), crude odds-ratio's of 2.7 (95% CI: 1.6-4.6) and 2.1 (95% CI: 1.2-3.6) were found for Ht and Hb respectively, when comparing "high" with "low" levels. The associations between Ht and Hb, and the occurrence of myocardial infarction were still present after controlling for covariates using multiple logistic regression models, entering the continuous variables with their exact values. After adjustment, mean corpuscular volume (MCV) also appeared to be correlated with infarction. Our results confirm the hypothesis that moderately high haematocrit and--to a lesser extent--haemoglobin and MCV-values are risk factors for the occurrence of myocardial infarction.

A large-scale prospective cohort study on diet and cancer in The Netherlands.

In 1986, a prospective cohort study on diet and cancer was started in The Netherlands. The cohort (n = 120, 852) of 55-69 year old men (48.2%) and women (51.8%) originates from 204 computerized municipal population registries. At baseline, participants completed a self-administered questionnaire on diet and potential confounding variables. In addition, about 67% of the participants provided toenail clippings. Cancer follow-up consists of record linkage to a pathology registry and to cancer registries. The initial interest is in stomach, colorectal, breast and lung tumors. A case-cohort approach is applied, in which detailed follow-up information of a random subcohort (n = 5000) provides an estimate of the person-time experience of the cohort. Exposure data of the subcohort will be combined with those of incident cases, yielding exposure-specific incidence rate ratios. The intraindividual variation in determinants is estimated by annually repeated measurements (n = 250) within the subcohort. The rationale, efficiency aspects and study characteristics are discussed.

Trends in incidence of adenocarcinoma of the oesophagus and gastric cardia in ten European countries.

BACKGROUND: In many western countries an increase in incidence of adenocarcinoma of the oesophagus and/or gastric cardia have been reported. The aim of this study was to describe and compare trends in incidence of adenocarcinoma of the oesophagus and gastric cardia in several areas of Europe, 1968-1995, using Eurocim (a database of cancer incidence and mortality data from 95 European cancer registries). METHODS: Time-trends in age-standardized incidence rates of adenocarcinomas of the oesophagus and gastric cardia are described in 11 population-based cancer registries from 10 countries in North, South, East, West and Central Europe, 1968-1995. The statistical significance of the time-trends in incidence was assessed using Poisson regression analysis. RESULTS: An increase in incidence of adenocarcinomas of the oesophagus and gastric cardia was observed in Northern Europe (Denmark), Southern Europe (Italy, Varese), Eastern Europe (Slovakia) and Western Europe (England and Wales, Scotland). In Central Europe (Switzerland, Basel) and in the cancer registries of Iceland (Northern Europe), France, Bas-Rhin and Calvados, Southern Ireland, and the Netherlands, Eindhoven (Western Europe) no rise in incidence was observed. The increase in incidence of adenocarcinomas of the oesophagus and gastric cardia was accompanied by a decrease in incidence of both adenocarcinomas and non-adenocarcinomas of the non-cardia part of the stomach in almost all of the 11 cancer registries studied. Increased histological verification of tumours of the oesophagus and stomach and improvement in precision of histological diagnosis may partly explain the increase in incidence of adenocarcinomas in some registries. CONCLUSIONS: This study, using Eurocim data, supports the findings from other time-trend studies of population-based cancer registries in western countries.

Silica exposure and lung cancer in ceramic workers: a case-control study.

The results are presented from a case-control study, concerning the possible relation between silica exposure in the Dutch fine ceramic industry and lung cancer. For this purpose 381 male, age-matched pairs of primary lung cancer cases and controls were selected from the pathology department of the University Hospital in the region, where two large ceramic companies are located. Information about employment in the ceramic industry was obtained from the personnel and financial administration departments of the two companies. On the basis of job titles a panel of occupational hygiene experts reached consensus about the qualitative exposures of each individual worker. Twenty one per cent of the cases were employed in the ceramic industry, compared with 19% of the controls (odds ratio 1.11; 95% Cl: 0.77-1.61). Although the average employment period of cases and their relative silica exposure surpassed those of controls, odds ratios for long duration of employment and considerable exposure to respirable silica dust did not reach statistical significance. After constructing a qualitative exposure index, based on the amount and duration of exposure, a tendency towards a positive correlation with lung cancer emerged. No relation between specific histological tumour cell types and working in the ceramic industry emerged. Although the study does not suggest a consistent cause-effect relation between silica exposure in the regional, Dutch fine ceramic industry and lung cancer, an increased risk for the high exposure group in the past can not be totally excluded.

Occupational cohort studies: the influence of design characteristics on the healthy worker effect.

A cross-sectional analysis of the relation between the estimated healthy worker effect (HWE), as measured by a total Standardized Mortality Ratio (SMR) less than 100, and relevant design characteristics in 270 published retrospective occupational cohort studies is presented. The majority of the reviewed studies showed a HWE, varying in SMR from 50 to 99 (mean: 84). The estimated HWE seemed to influence the final outcomes of the studies to a great extent. A tendency for a positive relation between the study size in terms of the number of exposed workers, total number of person-years of follow-up, and the HWE emerged. Studies with a comparatively short follow-up period had an increased chance of resulting in a HWE. Cross-sectional cohorts did not show a stronger HWE than open cohorts. Studies of chemical exposures revealed a fivefold excess of having a HWE compared with other studies.

The value of objective measurements to select patients who are malnourished.

Several studies have attempted to define nutritional parameters that can be used to select malnourished hospitalised patients for nutritional support. A combination of objective nutritional parameters was evaluated in a group of 50 patients selected for total parenteral nutrition on clinical grounds only and compared with a control group. This control group consisted of 38 patients who were admitted for elective minor surgical procedures such as varicectomy and hernia repair. On a subset of 18 objective nutritional measurements, discriminant analysis was performed. In the evaluation it was shown that a combination of albumin (ALB), prealbumin (PALB), total lymphocyte count (TLC) and the percentage of ideal weight (PIW) was the most useful combination of nutritional tests in discriminating a chosen malnourished (M) group and a control group who were declared not malnourished (NM). With this combination the patients were correctly classified in 93% with a sensitivity of 93% and a specificity of 94%.

Relevance of the expression of bcl-2 in combination with p53 as a prognostic factor in breast cancer.

BACKGROUND: Both the proto-oncogene bcl-2 and the tumour suppressor gene p53 are involved in the regulation of apoptosis. PATIENTS AND METHODS: We have investigated the prognostic value of the immunohistochemical expression of p53 and bcl-2 separately and in combination in a group of 345 breast cancer patients from one hospital with a long median follow-up of more than 10 years. RESULTS: Bcl-2 expression was not a prognostic factor. p53 was an independent prognostic factor for overall survival (p = 0.005) and for post-relapse survival (p = 0.006). Looking at bcl-2/p53 subgroups in the bcl-2 positive subgroup there was a large difference in both disease-free and overall survival between p53 negative and p53 positive patients. In the bcl-2 negative subgroup the p53 status was not a prognostic factor at all. CONCLUSIONS: p53 is an independent prognostic factor for overall survival and post-relapse survival. However, p53 status is only important in the bcl-2 positive subgroup.

pS2 is an independent prognostic factor for post-relapse survival in primary breast cancer.

BACKGROUND: The pS2 protein is involved in the maintenance of the integrity of the gastrointestinal tract. In breast cancer pS2 can be demonstrated in at least half of the tumors and probably reflects the functional status of ER. Several features make it likely that pS2 is involved in growth regulation. PATIENTS AND METHODS: We have investigated the value of immunohistochemical pS2 determination as a prognostic factor in 339 breast cancer patients with long follow-up from one hospital. RESULTS: A prognostic role for pS2 could not be demonstrated considering disease-free and overall survival, although in pS2-negative tumors a trend for less locoregional relapse was found. However, in multivariate analysis pS2 showed independent prognostic value for post-relapse survival. CONCLUSIONS: PS2 is an independent prognostic factor for post-relapse survival, most likely because it is a predictive factor for response to systemic therapy.

Modern life' in the epidemiology of inflammatory bowel disease: a case-control study with special emphasis on nutritional factors.

OBJECTIVE: The rising incidence of inflammatory bowel disease (IBD) since the Second World War coincides with profound changes of the dietary pattern. The aim of the study was to investigate the possible pathogenic role of some characteristic 'modern life' dietary factors in IBD. DESIGN: Case-control, studying risk factors in recently diagnosed cases, 290 with Crohn's disease and 398 with ulcerative colitis, compared with 616 population controls. Smoking, age, gender and education were taken into account by using logistic regression analysis. SETTING: Hospital cases and population controls. INTERVENTIONS: Questionnaires. MAIN OUTCOME MEASURES: Logistic regression-derived odds ratios. RESULTS: A positive association with cola drinks [OR: 2.2 (95% CI 1.5-3.1)], chewing gum [OR: 1.5 (95% CI: 1.1-2.1)] and chocolate consumption [OR: 2.5 (95% CI: 1.8-3.5)] and a negative association with citrus fruit consumption [OR: 0.5 (95% CI 0.3-0.7)] and the development of Crohn's disease were found. Consumption of cola drinks [OR: 1.6 (95% CI 1.1-2.3)] and chocolate consumption [OR: 2.5 (95% CI 1.8-3.5)] were positively associated with developing ulcerative colitis. There was a negative association between the intake of citrus fruits [OR: 0.5 (95% CI 0.4-0.8)] and 'having a stuffed pet' for a period longer than 5 years [OR: 0.6 (95% CI 0.4-0.9)] and developing the disorder. No association with the frequency of tooth brushing and developing IBD was found. CONCLUSION: All the nutritional items mentioned may be true risk factors or they just might be the expression of a modern life-style also involving other risk factors for the development of IBD which at the present are still unknown.

Binding function in relation to injury risk in downhill skiing.

Time-trend studies suggest that in the recent past, the use of modern equipment and adequately functioning ski bindings have had a preventive effect on injuries. The question of whether a further decrease of injury figures can still be expected from better binding adjustment is investigated in a case-control study (N = 1,148) conducted among Dutch skiers. Nonrelease of both bindings directly before injury was associated with a higher risk (odds ratio = 3.3) for lower extremity (LE) injury. Binding release before LE injury was highest (31%) among those for whom adjustment was performed and then confirmed with a test device. The proportion of nonrelease is highest for knee injuries. No effect on injury risk could be found for the time of adjustment, the method of adjustment, or the person performing the adjustment. Direct measurement of binding function seems indispensable. The use of rented or borrowed skis was associated with a higher risk (odds ratio = 1.9) for LE injury. The same holds for ignorance concerning the type of ski and the age of the skis and bindings. We concluded that binding adjustment still seems to be a risk factor open to manipulation. The efficacy of intervention aimed at better adjustment should be studied experimentally.

Prevalence rates of otitis media with effusion from 0 to 2 years of age: healthy-born versus high-risk-born infants.

In a prospective-longitudinal study, prevalence rates of otitis media with effusion (OME) were analysed in 150 healthy-born and 100 high-risk-born infants, aged 0-2 years. In order to determine OME, otoscopy and tympanometry were performed at 3-monthly intervals beginning at term date. The Maastricht Otitis Media with Effusion Study (MOMES) algorithm was used to standardize the diagnosis. The distribution of relevant background characteristics was similar in both groups except for gestational age and birth weight, which were significantly lower (P < 0.001) in the high-risk-born group. The ratio of unilateral:bilateral OME was 2:3. Prevalence rates of OME were strongly associated with age (P < 0.001). During the first months of life, OME prevalence rates increased rapidly in both groups, but did not differ significantly. However, from the age of 6 months on, OME prevalence rates of the high-risk group became significantly higher compared with the normal group (P < 0.05). The peak prevalence of OME (59% in the high-risk group versus 49% in the normal group) was observed around the age of 10 months. Although gradually decreasing prevalence rates were noted in both groups with aging, the differences between high-risk and normal infants remained, at least up to 24 months. In conclusion, OME is a very prevalent, age-dependent disorder during infancy, especially in high-risk infants. Peak prevalence of OME was found in the second half of the first year of life.

Risk factors of otitis media with effusion during infancy.

UNLABELLED: Associations of possible risk factors with prevalence of otitis media with effusion (OME) were prospectively studied in a cohort of 250 infants, aged 0-2 years. In order to determine OME, otoscopy and tympanometry were performed at 3-monthly intervals beginning at term date. Eighteen epidemiologically relevant features were inventoried by means of standardized questionnaires. Multivariate analysis controlled for possible confounding factors. Prevalence of OME was most strongly associated with age (P-value < 0.001). Other factors significantly associated with the prevalence of OME (P-value < 0.05) were gestational age, birth weight, breastfeeding, day-care attendance, number of siblings, season, and parent-reported ear infection, hearing loss, mouth breathing and common cold. No significance was found for gender, date of birth, passive smoking, family history of otitis media, parental socio-economic status and histories of snoring and consultation of a physician. IN CONCLUSION: both intrinsic and extrinsic factors appear to play an important role in the prevalence of OME. Some of the risk factors appeared to be time-dependent.

Determinants of medico-social functioning after total gastrectomy.

AIM: To describe medico-social functioning after total gastrectomy and the factors determining it. PATIENTS AND METHODS: In three medical rehabilitation centres, 173 consecutive patients (female/male = 62/111) after potentially curative total gastrectomy for gastric malignancy 206 days earlier (median, interquartile range = IQR 56-644) were evaluated for different pre- and post-operative parameters with potential influence on post-operative medico-social functioning as measured with the Edinburgh Rehabilitation Status Scale (ERSS). Parameters evaluated were: gender, age, time since operation, tumour stage, type of operation, clinical centre of admittance, haemoglobin, ferritin, albumin, presence of small bowel bacterial overgrowth, rapid oro-coecal transit, dyspepsia, early satiety, reflux, dysphagia, vomiting, a symptom based score, body mass index in health, at operation and on admission, weight loss since operation, calorie intake, bowel habits, and fat malassimilation. Independent influential factors for the ERSS were identified in a linear regression analysis. RESULTS: The median ERSS-score was 4 (IQR 2-6) on a scale from 0 (best) to 28 (worst). There was a significant difference in the ERSS-scores between the three different clinics. The ERSS-scores improved significantly with time since operation (ca. 22% per year). ERSS-scores were higher in patients with intestino-oesophageal reflux (+71%), with dyspepsia (+65%), or with dysphagia (+62%). CONCLUSION: Medico-social functioning was acceptable in this patient population. After total gastrectomy, dyspepsia, dysphagia, and intestinal reflux into the oesophagus need special attention.

Agoraphobic behavior in daily life: effects of social roles and demographic characteristics.

Agoraphobia is related to demographic characteristics and social roles. To unravel behavioral aspects from demographic characteristics, daily life situations were registered with the Experience Sampling Method for 65 panic patients with and without agoraphobia. Surprisingly, panic patients with and without agoraphobia did not differ as hypothesized in reported frequencies of visits to public places. Panic subjects with agoraphobia did, however, spend significantly more time at home and with their families than did panic patients without agoraphobia and normal controls. When adjusted for demographic variables such as sex, marital status, family life, and employment, no significant differences between panic patients with and without agoraphobia emerged on the avoidance variables of remaining at home or being with a family member. The lack of discrimination of the diagnosis on these crucial behavioral variables highlights the influence of demographic characteristics and social roles on agoraphobia in daily life. Such findings challenge current diagnostic conceptualizations that rely on retrospective reports by patients of the avoidance of public places. Moreover, reliance on retrospective reports obscured the important role of significant others for understanding etiology and course.

Regression analysis of prognostic factors in colorectal cancer after curative resections.

The clinical, laboratory, and pathologic data of 310 patients who had curative resections were prospectively collected and analyzed in a multiple stepwise regression model. Although several factors (i.e., venous invasion) were of importance in univariate analysis, the following conclusions reflect the outcome and relative importance of the regression analysis only. Blood loss as an initial symptom and duration of symptoms were associated with a better prognosis. Location of the primary tumor, age, and sex did not appear to have prognostic value. Observations during operation such as palpable lymph nodes, fixity to adjacent organs, and tumor spill were related to a diminished tumor-free survival. Laboratory data (hemoglobin, leukocytes, ESR, GGTP, SGOT, SGPT, LDH, total protein, CEA) were tested for their potential prognostic values. Only a preoperative low protein level or an elevated CEA level were associated with an increased risk of death due to recurrent tumor. The histopathologic features (stage and grade), with the exception of venous invasion, were of relative importance in the determination of prognosis. The aforementioned variables can be included in a prognostic index on the base of which high-risk groups suitable for adjuvant studies can be identified.

Prenatal diagnosis and fetal outcome of cystic adenomatoid malformation of the lung: case report and historical survey.

Diagnostic ultrasound allows prenatal diagnosis of cystic adenomatoid malformation of the lung from the second trimester onwards throughout pregnancy. If the diagnosis is made before the 24th week of pregnancy, counselling often results in termination of pregnancy. Whether or not this attitude is in agreement with good medical practice is discussed on the basis of our own experience and a review of the literature.