Cancer incidence and cancer mortality in relation to serum cholesterol.

We studied cancer incidence and mortality from cancer and coronary heart disease in relation to serum cholesterol levels in 92,710 individuals followed-up in the nationwide Swedish Cancer Register and the Swedish Cause of Death Register for 18-20 years. According to Cox's proportional hazard model, total cancer incidence and total cancer mortality were negatively correlated to serum cholesterol level (P less than .001). The negative correlations were most pronounced during the first years of follow-up. Cancer mortality data showed a stronger negative association to cholesterol than did incidence data during the first 10 years of follow-up (P less than .05). Mortality from coronary heart disease was positively correlated to serum cholesterol (P less than .001) during the entire follow-up. In contrast to most studies that were based on mortality data, our results of the comparison of incidence and mortality data of the same cohort are in agreement with those of a cholesterol-lowering effect of a preclinical cancer. Efforts by investigators and clinicians to lower serum cholesterol to prevent cardiovascular disease are, according to the present findings, not likely to increase cancer mortality risks but would extend life, irrespective of cause of death.

Prognostic significance of p53 nuclear and cytoplasmic overexpression in right and left colorectal adenocarcinomas.

The prognostic significance of nuclear and cytoplasmic p53 protein, detected immunocytochemically using CM1 and PAb 1801 antibodies, was evaluated in right-sided and left-sided colorectal adenocarcinomas from 293 patients. CM1 nuclear and cytoplasmic p53 accumulation occurred in 38 and 25% of cases, respectively. PAb 1801 nuclear staining occurred in 18%, with no cytoplasmic staining. CM1 expression either in the nucleus or in the cytoplasm was positively related to PAb 1801 expression (P < 0.001 and P = 0.009, respectively). The incidence of CM1 nuclear and cytoplasmic expression was more frequent in right-sided tumours (P = 0.023 and P = 0.034, respectively), while PAb 1801 nuclear staining was more common in left-sided tumours (P = 0.011). In survival analyses, CM1 nuclear overexpression in the right-sided tumours (P = 0.016) and CM1 cytoplasmic overexpression in left-sided tumours (P = 0.04) were prognostic indicators, independent of Dukes' stage, DNA ploidy, PAb 1801 expression and each other. Further analysis showed that the prognostic value of CM1 nuclear expression was greater in right-sided tumours than in left-sided tumours (P = 0.018). The nuclear and cytoplasmic p53 protein detected with CM1 and PAb 1801 may play different roles in tumour progression and provide prognostic indicators for right- and left-sided colorectal tumours.

c-erbB-2 expression and benefit from adjuvant chemotherapy and radiotherapy of breast cancer.

Frozen tissue from primary tumours of 152 premenopausal breast cancer patients, who participated in a trial comparing radiotherapy with adjuvant chemotherapy (cyclophosphamide, methotrexate, 5-fluorouracil, CMF), was analysed for c-erbB-2 protein expression, measured by flow cytometry. The relative risk of distant recurrence or death in the chemotherapy group as compared with the radiotherapy group was 3.0 (95% confidence interval (CI) 1.1-7.8) for patients whose tumours showed high c-erbB-2 levels and 0.87 (95% CI 0.43-1.7) for those with tumours with low levels of c-erbB-2 protein. Patients with highly proliferative tumours that did not overexpress c-erbB-2 benefited most, in terms of survival, from CMF. In addition, we found an increased risk of locoregional recurrence for tumours overexpressing c-erbB-2 when radiotherapy was replaced by chemotherapy.

ras p21 expression in relation to DNA ploidy, S-phase fraction and prognosis in colorectal adenocarcinoma.

ras p21 expression, as indicated by the monoclonal antibody ras 11, was estimated using immunohistochemistry on 69 primary colorectal adenocarcinomas. Also, DNA ploidy and S-phase fraction (SPF) were analysed with flow cytometry. Positive staining for ras 11 tended to be more common in DNA non-diploid tumours (P = 0.11), but was significantly correlated with high SPF (P = 0.038). Positive ras 11 staining, Dukes' stage, DNA ploidy and SPF were related to the recurrence-free interval of patients with Dukes' A-C tumours (P = 0.0014, P = 0.023, P = 0.035 and P = 0.040, respectively). ras 11 staining was a prognostic factor independent of both Dukes' stage and DNA ploidy (P = 0.011). The results indicate that pan ras p21 expression is associated with proliferative activity and has an independent prognostic value in colorectal adenocarcinoma.

Serum levels of cholesterol and ischemic heart disease mortality. The Värmland Study.

The objective of the Värmland Study was to examine how serum cholesterol can be used to predict short- and long-term ischemic heart disease (IHD) mortality, especially in women aged 65 or older. This prospective cohort study involved about 20 years of follow-up after a single determination of serum cholesterol and included participants in a health screening undertaken from 1962 to 1965 (48,076 men, 48,732 women). The main outcome measures were mortality from IHD, acute myocardial infarction (MI), and chronic ischemic heart disease (CIHD). An IHD mortality trend was associated with increasing cholesterol levels for people younger than 65 years, and was more pronounced for men than women. For people 65 years or older, there was a weak trend for men, but not even a tendency for women. Regarding acute MI, significant trends were observed for males as well as females, for young as well as old people. A mild CIHD mortality trend was observed for young men. Otherwise no significant trend was seen.

c-erbB-2 oncoprotein in relation to DNA ploidy and prognosis in colorectal adenocarcinoma.

Overexpression of the c-erbB-2 oncogene has been demonstrated in a variety of tumours, including colorectal tumours. In breast carcinoma, c-erbB-2 overexpression is associated with DNA ploidy, some other prognostic indicators, and unfavourable survival prospects. However, there is little such information available regarding colorectal tumours. In this study, c-erbB-2 was analysed retrospectively by immunohistochemistry in 293 primary colorectal adenocarcinomas to assess its relation to DNA ploidy, S-phase fraction, other prognostic factors, and patient survival. Using the monoclonal antibody NCL-CB11, we found that 23% of the tumours were strongly c-erbB-2 positive, while 36% showed weak expression. The highest frequency of c-erbB-2 expression was 81% in DNA tetraploid tumours, compared to 63% in aneuploid and, 53% in diploid tumours (test for heterogeneity, p = 0.031). Overexpression of c-erbB-2 indicated a favourable prognosis in patients with DNA aneuploid tumours (p = 0.0088), but not in those with diploid or tetraploid tumours. The prognostic value of c-erbB-2 in DNA aneuploid tumours remained even after adjustment for Dukes' stage (p = 0.027). The results suggest that a combination of c-erbB-2 expression and DNA ploidy may improve the identification of patients' risk of cancer death.

Overexpression of ras is an independent prognostic factor in colorectal adenocarcinoma.

The expression of ras was investigated by using immunohistochemistry in 245 primary colorectal adenocarcinomas and 49 corresponding metastases in the lymph nodes. One hundred and forty-four (59%) of the primary tumours presented as ras positive and 37 (76%) were positive in metastases. The ras expression was positively related to cell proliferation (p=0.01) and significantly increased in tumours with aneuploidy (68%) compared to tumours with diploidy (51%) and tetraploidy (53%, p=0.01). The frequency of ras expression was increased from Dukes' stage A to stages B-D (41% vs 62%, p=0.01). ras expression was compared in 40 paired primary tumours and their corresponding metastases, and the difference in expression did not reach statistical significance (73% vs 83%, p=0.32). In survival analyses, ras overexpression predicted a poor prognosis independent of Dukes' stage, DNA ploidy and S-phase fraction (p=0.049). We did not find any significant relationship between ras expression and patients' sex, age, tumour location, growth pattern, differentiation, p53 expression or heat shock protein. The results indicate that the alteration of ras expression may be involved in the instability of DNA and cellular overproliferation, but not in the progression to advanced stage and the development of metastases. The expression of ras was an important biological marker for evaluating the prognosis in patients with colorectal adenocarcinoma.

Interrelations of clinicopathologic variables and their prognostic value in colorectal adenocarcinoma.

We analyzed the interrelations of sex, age, tumor site, Dukes' stage, growth pattern and differentiation, and their prognostic value in 293 patients with primary colorectal adenocarcinoma. Simultaneously, growth pattern, differentiation, DNA and S-phase fraction (SPF) in paired primary tumors and lymph node metastases from 97 colorectal cancer patients were compared. The results revealed that poorly differentiated and mucinous tumors, as against well/moderately differentiated tumors, were frequently located in the proximal colon, and their frequencies were increased as Dukes' stage advanced (p=0.03). Tumor differentiation was usually identical in primaries and corresponding metastases (p=0.002), but this was not true of tumor growth pattern, DNA ploidy or SPF. In multivariate survival analyses, Dukes' stage provided strongly prognostic information (p<0.001) and mucinous tumors tended to predict worse survival (p=0.08).

Smoking-adjusted incidence of lung cancer among Swedish men in different occupations.

The Swedish Cancer-Environment Register was used to study the relation between occupation and lung cancer risk during the period 1961-79 in 1.6 million men aged 30-64 years in 1960. By adding information concerning smoking habits from a sample of 1% of the Swedish population, smoking-adjusted standardized incidence ratios (SIR) were estimated for different occupational categories according to the population census of 1960. Smoking-adjusted excess risks (p less than 0.01) were found in assemblers and machine erectors, drivers, miners, packers and longshoremen as well as in sheetmetal workers. Significantly fewer lung cancer cases than expected were seen in artists and writers, chemical and cellulose workers, farmers, farm workers, forestry workers, public administrators and in teachers. As a result of a high prevalence of smoking, the smoking-adjusted SIR was markedly lower than the unadjusted SIR in artists and writers, drivers, mechanics and repairmen, members of the armed forces and painters. The opposite situation was seen for clergy, farmers and forestry workers.

Mortality in relation to cigarette and pipe smoking: 16 years' observation of 25,000 Swedish men.

In a random sample of 25,129 Swedish men who responded to a questionnaire on smoking habits in 1963 the cause specific mortality was followed through 1979. In the cohort, 32% smoked cigarettes, 27% a pipe, and 5% cigars. There were clear covariations (p less than 0.001) between the amount of tobacco smoked and the risk of death due to cancer of the oral cavity and larynx, oesophagus, liver, pancreas, lung, and bladder as well as due to bronchitis and emphysema, ischaemic heart disease, aortic aneurysm, and peptic ulcer. Pipe smokers showed similar risk levels to cigarette smokers. There was a close to linear increase in lung cancer risk in relation to the amount of tobacco smoked for cigarette, pipe, and cigar smokers, respectively. An increasing risk of ischaemic heart disease with amount smoked was seen among both cigarette and pipe smokers. A similar fraction of inhalers in Swedish cigarette and pipe smokers may explain the similarity in risks.

Mortality among male and female smokers in Sweden: a 33 year follow up.

STUDY OBJECTIVE: It is still unclear if men and women are equally susceptible to the hazards of tobacco smoking. The objective of this study was to examine smoking related mortality among men and women. DESIGN: In 1963 a questionnaire concerning tobacco smoking habits was sent out to a random sample from the 1960 Swedish census population. Date and cause of death have been collected for the deceased in the cohort through 1996. SETTING: Sweden. PARTICIPANTS: The survey included a total of 27 841 men and 28 089 women, aged 18-69 years. The response rate was 93.1% among the men and 95.4% among the women. MAIN RESULTS: After adjustment for age and place of residence positive associations were found between cigarette smoking and mortality from ischaemic heart disease, aortic aneurysm, bronchitis and emphysema, cancer of the lung, upper aerodigestive sites, bladder, pancreas in both men and women, but not from cerebrovascular disease. When the effect of amount of the cigarette consumption was considered, female smokers displayed, for example, slightly higher relative death rates from ischaemic heart disease. However, no statistically significant gender differential in relative mortality rates was observed for any of the studied diseases. CONCLUSIONS: Women and men in this Swedish cohort seem equally susceptible to the hazards of smoking, when the gender differential in smoking characteristics is accounted for. Although the cohort under study is large, there were few female smokers in the high consuming categories and the relative risk estimates are therefore accompanied by wide confidence intervals in these categories.

Direct identification of pure Penicillium species using image analysis.

This paper presents a method for direct identification of fungal species solely by means of digital image analysis of colonies as seen after growth on a standard medium. The method described is completely automated and hence objective once digital images of the reference fungi have been established. Using a digital image it is possible to extract precise information from the surface of the fungal colony. This includes color distribution, colony dimensions and texture measurements. For fungal identification, this is normally done by visual observation that often results in a very subjective data recording. Isolates of nine different species of the genus Penicillium have been selected for the purpose. After incubation for 7 days, the fungal colonies are digitized using a very accurate digital camera. Prior to the image analysis each image is corrected for self-illumination, thereby gaining a set of directly corresponding images with respect to illumination. A Windows application has been developed to locate the position and size of up to three colonies in the digitized image. Using the estimated positions and sizes of the colonies, a number of relevant features can be extracted for further analysis. The method used to determine the position of the colonies will be covered as well as the feature selection. The texture measurements of colonies of the nine species were analyzed and a clustering of the data into the correct species was confirmed. This indicates that it is indeed possible to identify a given colony merely by macromorphological features. A classifier (in the normal distribution) based on measurements of 151 colonies incubated on yeast extract sucrose agar (YES) was used to discriminate between the species. This resulted in a correct classification rate of 100% when used on the training set and 96% using cross-validation. The same methods applied to 194 colonies incubated on Czapek yeast extract agar (CYA) resulted in a correct classification rate of 98% on the training set and 71% using cross-validation.

[Metachronous liver metastases treated with repeated liver resections and chemotherapy]. / Metakrone levermetastaser behandlet med gentagne leverresektioner og kemoterapi.

A patient with a radically resected rectosigmoid cancer underwent two liver resections for metachronous metastases. When a third hepatic recurrence was diagnosed, further surgery was considered technically impossible, and the patient was given chemotherapy with 5-fluorouracil and folinic acid. He went into complete remission, and seven and a half years after the resection for colorectal cancer no metastases in the liver can be shown by ultrasonography or CT scan. The patient has normal CEA, and is at work.

Relationship between Quetelet's index and cancer of breast and female genital tract in 47,000 women followed for 25 years.

The relationship between Quetelet's index and subsequent risk for cancer of endocrine target organs was studied in a cohort of 47,003 women, examined for height and weight in the years 1963-65, and followed up in the Swedish Cancer Register until 1987. High Quetelet's index was associated with a decreased risk for breast cancer among women less than 55 years of age at risk, while a high Quetelet's index predicted an increased risk among older women. Among women > or = 55 years of age, the excess relative risk for breast cancer associated with high Quetelet's index declined significantly during the follow-up period. Cancer of the ovaries and the uterine cervix were not significantly related to Quetelet's index in any age group. In women > or = 55 years of age, the relative risk for cancer of the uterine corpus associated to Quetelet's index was higher than that for breast cancer, and this association persisted during the entire follow-up period of more than 20 years. In spite of the fact that endometrial cancer is less common than breast cancer, because of the stronger relation between overweight and endometrial cancer, more endometrial cancer would be attributable to obesity than breast cancer.

Time trends in occupational risks of lung cancer among Swedish men from 1961-1979.

Using data from the Swedish Cancer-Environment Register, time trends in the standardized incidence ratio (SIR) for lung cancer 1961-1979 were studied in different occupations. After adjustments for differences in the SIR with respect to year of birth, only the decreasing trends for blacksmiths and members of the armed forces as well as increasing trends for foundry workers and construction machine operators were significant (p less than 0.05). For bakers and pastry cooks, there was a significant interaction between year of birth and observation period in relation to SIR. Data on smoking habits, obtained from a sample of the population, did not seem to explain the trends.

Breast cancer risk in relation to serum cholesterol, serum beta-lipoprotein, height, weight, and blood pressure.

The relation between breast cancer risk and serum levels of cholesterol and beta-lipoprotein (BLP), height, weight, Quetelet's index and blood pressure was studied in a cohort of 46,570 Swedish women less than 75 years of age. The cohort was examined between 1963 and 1965 and followed up in the Swedish Cancer Registry until 1983. During this period 1,182 cases of breast cancer were reported. Of those, 196 were reported among women less than 50 years of age. Statistically significant positive associations were observed between height, weight, and systolic blood pressure and breast cancer risk. No clear trend in cancer risk related to serum cholesterol or BLP was seen in the total material. In a stepwise Cox multiple regression analysis only the associations with height and blood pressure remained significant. Among women, having their cancer diagnosed before the age of 50, higher Quetelet's index was associated with a lower cancer risk, whereas a positive correlation was seen among women greater than or equal to 50 years. In the group of younger women a high BLP level was associated with an increased risk of breast cancer. This relation became even stronger when studied in a multivariate analysis, which also showed a negative correlation between serum cholesterol and cancer risk.

Risk of stomach cancer in association with serum cholesterol and beta-lipoprotein.

The relation between serum levels of cholesterol and beta-lipoprotein (BLP) and stomach cancer risk was studied in a Swedish cohort of 92,710 individuals. The cohort was examined with a single measurement of cholesterol and BLP between 1963 and 1965 and followed up in the Swedish Cancer Registry until 1983. During the follow-up period 576 stomach cancers were reported. The risk of stomach cancer was negatively correlated to serum levels of cholesterol with a relative risk (RR) of 0.85 for every 40 mg/dl increase of cholesterol (p less than 0.001) and to BLP with an RR of 0.90 for every 3 units increase of BLP (p less than 0.01) when analysed one at a time. In a multiple regression analysis, however, only the relation to cholesterol remained statistically significant. The risk association seemed to be most pronounced between the third and fifth years of follow-up.

Prognostic significance of DNA measurements in 409 consecutive breast cancer patients.

Four hundred nine consecutive breast cancer patients were studied retrospectively. Microspectrophotometric DNA measurements were performed using archival, fine-needle slide preparations upon which the primary diagnoses had been based 8 to 13 years earlier. The DNA distribution patterns of the tumor cell populations were analyzed according to various criteria and the cytochemical data were correlated to the clinical course, defined as distant recurrence-free survival. The results demonstrated a strong relationship between nuclear DNA content of the breast cancer cells and prognosis. Tumors exhibiting DNA values within the limits of normal tissues (DNA euploidy) were found to be correlated with a favorable prognosis. In contrast, tumors with increased and scattered DNA values (DNA aneuploidy) were found indicative of poor prognosis. This was found to be the case regardless whether the percentage of cells above 2.5c or 5c, DNA index/modal value, or the histogram typing according to Auer et al were utilized to discriminate low-grade from high-grade malignant cases. All of these DNA variables were also shown to be significantly correlated. With the aid of the Cox regression method, the additional prognostic value of any given variable was tested against the others. The statistical analyses showed that the histogram typing gives significant prognostic information in addition to that provided by any other variable. In conclusion, the current study demonstrates that tumor nuclear DNA content is a strong indicator of prognosis in patients suffering from invasive breast adenocarcinoma. However, the results also show that simple determination of the stemline position is not the optimal DNA measure of intrinsic tumor malignancy potential. The fraction of cells scattered outside the modal peaks of the histograms are of utmost importance for adequate cytochemical malignancy grading in breast carcinomas.