Alcohol consumption and bladder cancer risk: results from The Netherlands Cohort Study.

Although several epidemiologic studies have been conducted on alcohol consumption and bladder cancer risk, the risk according to quantity and type of alcohol consumed is not clear. The authors investigated these associations in a large prospective cohort study on diet and cancer among 120,852 subjects in the Netherlands aged 55-69 years at baseline (1986). Subjects completed a questionnaire on risk factors for cancer, including alcohol consumption. Follow-up for incident cancer was established by record linkage to cancer registries. The case-cohort analysis was restricted to a follow-up period of 6.3 years and was based on 594 cases with bladder cancer and 3,170 subcohort members. The authors corrected for age and smoking in multivariable analyses. The incidence rate ratios for men who consumed <5, 5-<15, 15-<30, and > or =30 grams of alcohol per day were 1.49, 1.52, 1.16, and 1.63 compared with nondrinkers, respectively (p for trend = 0.13). Alcohol consumed from beer, wine, and liquor was associated with moderately elevated risks, although most were not statistically significant. The incidence rate ratios for women varied around unity. The results of this study do not suggest an important association between alcohol consumption and bladder cancer risk.

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.

Predictive value of parent-reported symptoms in the assessment of otitis media with effusion during infancy.

OBJECTIVE: To determine the predictive value of parent-reported symptoms in the assessment of otitis media with effusion (OME) during infancy. DESIGN: Prospective longitudinal study that compared the results of questionnaire-based parental reports with the state of the middle ear assessed by otoscopy and tympanometry at 3-month intervals from birth to the age of 2 years. SETTING: Outpatient Department, University Hospital Maastricht, The Netherlands. SUBJECTS: One hundred and fifth healthy-born infants. MAIN OUTCOME MEASURES: Sensitivity, specificity, positive and negative predictive values of parent-reported ear infection, hearing loss, mouth breathing, snoring and common cold. RESULTS: Prevalence rates showed the following ranges: OME, 39%-53%, parent-reported ear infection, 2%-20%, hearing loss 2%-7%, mouth breathing, 30%-41%, snoring, 31%-41% and common cold, 65%-81%. Common cold demonstrated the highest sensitivity (83%) with a low specificity of 36%. Hearing loss gave the highest positive predictive value (PPV) (70%) with a moderate negative predictive value (NPV) (54%). PPV increased with the number of anamnese questions answered positively. CONCLUSIONS: The diagnostic value of parent-reported ear infection, hearing loss and common cold was found to be limited. Combinations of positively-reported symptoms gives increased diagnostic validity while the absence of parent-reported symptoms does not necessarily indicate the absence of OME.

Chronic otitis media with effusion during infancy, have parent-reported symptoms prognostic value? A prospective longitudinal study from 0 to 2 years of age.

As a part of a prospective study (age, 0-2 years), the prognostic value of parent-reported symptoms relative to chronic otitis media with effusion (COME) was examined in a group of 122 infants. The occurrence of hearing loss, ear infection, mouth breathing, snoring and common cold was inventoried using a standardised questionnaire filled in by parents at 3-monthly intervals. Tympanometric and otoscopic records were combined for assessment of middle ear status. Subjects were categorized into three groups: none (n = 13), mild (n = 78) and severe (n = 31) COME. Analysis revealed that all symptoms in the first year of life were significantly associated with severe COME. In the second year, only hearing loss was associated with a higher risk for severe COME. The risk for severe COME increased when symptoms were combined. In conclusion, a questionnaire based on only symptoms during the first year of life may assist in screening and managing severe COME.

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.

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.

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.

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.

MIB-1 labelling index is an independent prognostic marker in primary breast cancer.

The proliferative activity of a tumour is considered to be an important prognostic factor in primary breast cancer. We have investigated the prognostic value of the MIB-1 labelling index in 341 patients with primary breast cancer and compared the results with the S-phase fraction in 220 patients of the same cohort. All patients were treated in one hospital and had a median follow-up of 128 months. No correlation between MIB-1 labelling and S-phase fraction could be demonstrated. MIB-1 had prognostic value for disease-free survival in the whole group of patients (P < 0.001) and in the node-negative subgroup (P < 0.001). In multivariate analysis, MIB-1 was an independent prognostic factor (P = 0.004) besides axillary lymph node status (P = 0.001). In univariate analysis high S-phase fraction was associated with decreased overall survival (P = 0.04); however, not in multivariate analysis. Moreover, S-phase fraction had a borderline prognostic significance for post-relapse survival in multivariate analysis (P= 0.08). Thus, in conclusion, the growth fraction of a tumour as determined by the MIB-1 labelling index is an important prognostic factor in patients with primary breast cancer.

CD44v6 is not a prognostic factor in primary breast cancer.

BACKGROUND: CD44 is an adhesion molecule and represents a highly variable family of isoforms. The isoform CD44v6 has been associated with metastasis formation and poor prognosis in animal models and human colon cancer. Results of studies in primary breast cancer are relatively small and contradictory. PATIENTS AND METHODS: The immunohistochemical expression of CD44v6 was studied in a series of 338 patients with primary breast tumours, uniformly staged and treated in a single center with a long median follow-up of 128 months. The prognostic significance of CD44v6 as well as the correlation with several clinicopathological features were analysed. RESULTS: Two hundred nineteen of 338 (64.8%) of the breast cancer were CD44v6-positive (> 5% of tumour cells with positive staining). CD44v6 expression had no value for prognosticating disease-free or overall survival at this or any other cut-off point. CONCLUSION: CD44v6 expression is not a prognostic factor in primary breast cancer.

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.

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.

High incidence of inflammatory bowel disease in The Netherlands: results of a prospective study. The South Limburg IBD Study Group.

PURPOSE: To gain recent epidemiologic information about inflammatory bowel disease in The Netherlands, a prospective study over four years (1991-1995) was performed. METHODS: The incidence of inflammatory bowel disease and its subgroups was examined using standardized reports of newly diagnosed patients. A separate study compared the Inflammatory Bowel Disease Registration and computerized diagnostic files of a subgroup of general practitioners with the aim of estimating completeness of case ascertainment. RESULTS: The following mean incidence rates (per 100,000 inhabitants and year) were found: 6.9 (95 percent confidence interval, 5.9-7.9) for Crohn's disease, 10 (95 percent confidence interval, 8.7-11.2) for ulcerative colitis (23 percent of these with ulcerative proctitis), and 1.1 (95 percent confidence interval, 0.7-1.5) for indeterminate colitis. In the age category 20 to 29 years, the incidence rate of Crohn's disease with small-bowel involvement was higher in females than in males. In extended ulcerative colitis, a male preponderance was observed in the older age groups. Estimated case ascertainment was 78 percent. CONCLUSIONS: Compared with recent studies in neighboring countries, the observed age and gender standardized incidence rates are high in the south of The Netherlands. Completeness of case ascertainment might have contributed to this observation; however, case ascertainment was low in ulcerative proctitis. In the study area, differences in age and gender standardized incidence rates and in disease localizations could be compatible with an influence of environmental risk factors.

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.

Efficacy and safety of prophylactic cranial irradiation in patients with small cell lung cancer.

BACKGROUND: Prophylactic cranial irradiation (PCI) as part of the treatment regimen for patients with limited stage small cell lung cancer (SCLC) remains controversial. The present study was performed to analyze the efficacy and safety of PCI in patients with limited stage SCLC who achieved complete remission. PATIENTS AND METHODS: Between 1983 and 1993, thirty-nine patients with limited stage SCLC who had shown complete remission after chemotherapy were enrolled prospectively into the non-randomized study. Eighteen of them received PCI (PCI+), while 21 did not (PCI-). Pretreatment CT or MRI of the brain was performed in all patients. Patients were prospectively evaluated by a neurologist at regular intervals. RESULTS: Three PCI+ patients and seven PCI- patients developed brain metastases. The frequencies of brain metastases were not significantly different between the groups (Fisher's exact test, p = 0.207), but brain metastases in PCI+ patients tended to occur later (log rank, p = 0.008). Overall survival was significantly longer in PCI+ patients (log rank, p < 0.001). Early toxicity consisted of headache, nausea, fatigue, concentration problems and alopecia. These symptoms and signs were mild and usually reversible within a few months. Late toxicity was studied in patients whose survival exceeded two years. Seven PCI+ patients survived for more than two years, while no PCI- patients survived for more than two years. Memory problems were seen in six of the seven patients. These problems were non-disabling and, once established, remained stable for months to years. The most prominent radiologic abnormalities were cortical atrophy and leukoencephalopathy, found in four of the five patients who underwent radiologic follow-up examination. CONCLUSIONS: This non-randomized study suggests that PCI may be effective by decreasing the frequency of brain metastases and by increasing the brain metastasis-free survival and overall survival, with a minor risk of clinical and radiologic neurotoxicity.

Prognostic significance of radial margins of clearance in rectal cancer.

A retrospective review of 325 patients was undertaken to analyse whether involvement of the radial resection margin (RRM) could predict locally recurrent disease or distant metastases in patients who had curative surgery for rectal or rectosigmoid cancer. Information on the RRM was available in 253 patients. The RRM was involved in 31 (12 per cent). Nine of these 31 patients developed local recurrence (29 per cent), while only 17 local recurrences were diagnosed in 217 patients (8 per cent) without involvement of the RRM (P < 0.01). At 2 years the overall local recurrence rate was 10 per cent. Distant metastases were diagnosed in 46 patients (18 per cent) and RRM involvement was identified as a prognostic factor depending on lymph node involvement (N stage) (P = 0.02). Local recurrence and some distant metastases result from microscopically incomplete resection. Assessment of the radial depth of tumour invasion by careful histological examination of x791p4ecimen may be used for selection of patients for adjuvant radiotherapy and/or chemotherapy.

Predictors for hidden problem drinkers in general practice.

In The Netherlands general practice attenders are not usually questioned about their drinking habits. The objective of this study was to determine to what extent easily available data (e.g. age, gender) can be used to identify categories of patients who are at risk of problem drinking as a preliminary to more intensive screening. Sixteen practices with a total population of 32,000 patients were involved in the study. All problem drinkers known by their GPs and a random sample of one in ten patients not thought to be problem drinkers were admitted to the study at their first surgery visit during a 1-year period. A screening questionnaire was used to find hidden problem drinkers amongst the individuals thought to be non-problem drinkers. The overall response rate was 91% (n = 1405). Problem drinking was detected in 6% (n = 82) of the group regarded by the GPs as non-problem drinkers (n = 1283). Male gender, smoking, life events and chronic social problems were the strongest non-alcohol-related predictors of hidden problem drinking. We conclude that a pre-selection of patients with a greater risk of problem drinking can be made without information related directly to alcohol. Case-finding in this category is much more effective and probably much more acceptable both to the GP and the patients, than the screening of all patients.

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.

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.

Endocrine cells in colorectal adenocarcinomas: incidence, hormone profile and prognostic relevance.

The occurrence of endocrine cells in 350 cases of colorectal adenocarcinoma was studied by immunohistochemistry for chromogranin A (CGA). The hormone profile of endocrine tumor cells, the correlation between endocrine differentiation and presence of other colorectal epithelial-cell lineages and the prognostic relevance of endocrine differentiation in colorectal cancer were investigated. CGA-positive tumor cells were found in 30% of cases, 21% showing moderate positivity and 9.0% extensive positivity. Of CGA-positive tumors, 70% additionally produced neurohormones, mainly indigenous to normal colorectal epithelium: 55% showed immunoreactivity for glucagon-like substances, 20% for serotonin and 10% for somatostatin, PYY and HCG. No immunoreactivity was found for various neurohormones not normally produced by colorectal endocrine cells. CGA-positive tumors tended to be more aggressive than CGA-negative tumors. Especially, tumors with extensive CGA positivity showed shorter survival, which was most apparent within Dukes' stage C. In multivariate analysis, extensive CGA positivity was an independent indicator of poor prognosis. CGA immunoreactivity significantly correlated with mucin production, but not with expression of secretory component (SC), a columnar-cell marker. Mucin production significantly correlated with SC expression. Tumors positive for CGA but not for mucin and/or SC showed the worst prognosis. SC expression was a relatively favorable feature, and mucin-producing tumors showed intermediate behavior.