Biomedical subjects

G Steineck

Publications and source records attributed to G Steineck.

At least 37 records · Page 2Linked to original sources

PubMed2000

Prognostic and treatment-predictive factors-is there a difference?

The terms risk factor, prognostic factor and predictive factor are often imprecisely used. We defined a prognostic factor as a patient characteristic that identifies subgroups of untreated patients having different outcomes, and a factor predictive of treatment effect as a patient characteristic that identifies subgroups of treated patients having different (as a consequence of treatment) outcomes. To illustrate this, theoretical graphical examples were constructed and data from the literature on prostate cancer were used to substantiate the theoretical examples. In most situations, but not necessarily always, a prognostic factor is also pre- dictive of the effect of specific treatments. Whether a prognostic factor is also predictive of treatment effect or not can only be assessed in a valid comparative setting such as in a randomized trial. A factor that is predictive for treatment effect may not be predictive for another treatment. Prostate Cancer and Prostatic Diseases (2000) 3, 265-268

Journal Article↗

PubMed2000

Epidemiology and etiology of premalignant and malignant urothelial changes.

Bladder neoplasms are common around the world. Incidences are particularly high in the Nile River Valley secondary to schistosomiasis, which is frequently associated with the development of squamous cell carcinoma similar to that of other chronic inflammatory processes of the lower urinary tract. However, elsewhere, most bladder tumors are of the urothelial (transitional) cell type. There is a marked male predominance and there are extensive racial differences. It is predominantly a neoplasm that occurs in patients aged >50 years. Urothelial carcinomas comprise two distinct diseases both biologically and molecularly: a low-grade papillary tumor which frequently recurs; and a high-grade malignancy which can present as dysplasia or carcinoma in situ, but frequently presents as invasive disease. However, epidemiological investigations of urothelial malignancies have generally not distinguished between preneoplastic and invasive neoplasms or between these two types of urothelial neoplasms. It is recommended that future studies should distinguish between these entities. The most common etiologic factor of urothelial malignancies besides schistosomiasis is cigarette smoking. In addition, numerous specific chemicals have been identified as bladder carcinogens in humans, some relating to specific occupational exposures. Bladder carcinogens include aromatic amines and amides, such as 4-aminobiphenyl, benzidine, 2-naphthylamine and phenacetin-containing analgesics, and certain cancer chemotherapeutic agents, such as phosphoramide mustards. More recently, occupational exposure to various combustion gases, such as diesel exhaust, has been related to an increased risk of developing bladder neoplasms. Also, exposure to chlorination by-products in drinking water and to arsenic has been suggested as increasing the risk of bladder neoplasia. As numerous specific chemicals appear to be related to the development of bladder tumors, various polymorphisms of enzymes involved in their metabolism have been suggested as affecting the susceptibility to their carcinogenicity. This has been particularly true with respect to the role of acetyltransferases in relation to aromatic amine carcinogenesis. Dietary influences have also been suggested as affecting bladder neoplasia susceptibility. Various heterocyclic amines generated by pyrolysis of food have been suggested as potential dietary factors increasing the risk of bladder cancer, particularly in relation to the ingestion of red meat. Despite the existence of several identifiable factors that increase or decrease the risk of bladder cancer, many patients have no known carcinogens or risk factors.

Adenocarcinoma↗

PubMed2000

Prevention and treatment of urothelial premalignant and malignant lesions.

Bladder cancer is believed to develop through reversible premalignant stages followed by irreversible steps, and ending in invasive cancer giving rise to distant metastases. Because of the variation in the clinical course it has also been suggested that different forms of cancer develop along different molecular pathways leading to tumor presentations of various malignant potential. Today we treat and prognosticate bladder cancer on the basis of clinical and histologic findings that are insufficient to assess all the biologic potential of these tumors. Understanding the pathogenesis of bladder cancer might lead to a more precise identification of particular tumors with regard to clinical aggressiveness, resulting in individualized strategies for treatment and prophylaxis. Bladder cancer is seldom diagnosed in its preclinical stage, it is instead detected at cystoscopy and virtually never recognized as an incidental finding on autopsy. Therefore its "natural history" largely reflects that of "treated" disease. The true incidence of premalignant and malignant epithelial changes is not known. Incidences of hyperplasia and dysplasia of approximately 10% and approximately 5%, respectively and only occasional findings of cancer itself were reported in two autopsy series. Urothelial dysplasia is generally believed to be premalignant and a putative precursor of invasive cancer but unfortunately there has been a lack of standardization in terms of terminology and diagnosis. There is also a need for an agreed definition of the boundary between premalignancy, i.e. urothelial changes that have some but not all the features of carcinoma in situ, and malignancy, especially when considering potentially harmful treatments to prevent this transition. Most new diagnostic tools available and being tested today compare new detection techniques with traditional methods such as cytology or conventional histology of malignant rather than premalignant changes. There is probably also a short preclinical latency, as implied by the incidental findings of bladder cancer at autopsy, which makes it necessary to define how and when to promote early detection and treatment. Future studies therefore have to concentrate on methods for early detection of disease as well as characterization of host susceptibility, evaluation of exposure to carcinogens and potential effects of preventive measures. It is also likely that the improved tools of molecular prognostication will allow us to design trials more precisely in order to tailor therapeutic strategies.

Animals↗

PubMed2000

p53 intron 7 polymorphisms in urinary bladder cancer patients and controls. Stockholm Bladder Cancer Group.

A C-->T polymorphism in intron 7 of the human tumour suppressor gene p53 was studied in 159 urinary bladder cancer patients and 171 non-cancer controls. The polymorphism was found in 15% of both patients and controls, suggesting that it has no relevance in urinary bladder cancer pathogenesis or aetiology. A second polymorphism, a T-->G change located 20 bp downstream of the C-->T change, was found in all samples with the C-->T change. Our findings indicate that the C-->T and the T-->G changes occur simultaneously and belong to the same allelotype.

Adult↗

PubMed2000

Bladder cancer: allelic deletions at and around the retinoblastoma tumor suppressor gene in relation to stage and grade.

Inhibition of the retinoblastoma tumor suppressor gene (RB) is probably important in the pathogenesis of urinary bladder cancer. Little information is available concerning allelic loss on 13q11 to 13q32 and its relation to grade and stage. In a population-based study, freshly frozen tissue was collected from all new cases of urinary bladder cancer in the Stockholm region during 1995-1996. Here we report the occurrence of loss of heterozygosity (LOH) at seven sites in 13q11 to 13q32 as analyzed in 236 cases by a fluorescent multiplex PCR-based on tumor DNA and peripheral blood. For each site, about 30% of the cases were not informative because of homozygosity. Replication errors were detected in 4% (17 cases). LOH was found in 21 (at 13q11-12.1) to 32% (at 13q14.3 in RB) of the informative cases. A correlation was found between the prevalence of LOH at all observed loci and stage and grade, respectively, and it was statistically significant for 13q14.3. LOH at RB was found in Ta as well as grade 1 tumors. Also, a statistically significant correlation was found between the number of loci with LOH at 13q and tumor stage and grade, respectively. Typically an altered RB function is related to the expected clinical course of urinary bladder cancer, but allelic loss including the gene also occurs in low grade and low stage tumors. An altered RB function probably is not necessary for a malignant transformation of urothelial cells. The causal direction of the relation between the quantity of the deleted DNA and tumor aggressiveness is not clear.

Alleles↗

PubMed1999

Vaginal changes and sexuality in women with a history of cervical cancer.

BACKGROUND: In women with cervical cancer, treatment causes changes in vaginal anatomy and function. The effect of these changes on sexual function and the extent, if any, to which they distress women are not known. METHODS: In 1996 and 1997, we attempted to contact 332 women with a history of early-stage cervical cancer (age range, 26 to 80 years) who had been treated in 1991 and 1992 at the seven departments of gynecological oncology in Sweden and 489 women without a history of cancer (controls) to ask them to answer an anonymous questionnaire about vaginal changes and sexual function. RESULTS: We received completed questionnaires from 256 of the women with a history of cervical cancer and 350 of the controls. A total of 167 of 247 women with a history of cancer (68 percent) and 236 of 330 controls (72 percent) reported that they had regular vaginal intercourse. Twenty-six percent of the women who had cancer and 11 percent of the controls reported insufficient vaginal lubrication for sexual intercourse, 26 percent of the women who had cancer and 3 percent of the controls reported a short vagina, and 23 percent of the women who had cancer and 4 percent of the controls reported an insufficiently elastic vagina. Twenty-six percent of the women who had cancer reported moderate or much distress due to vaginal changes, as compared with 8 percent of the women in the control group. Dyspareunia was also more common among the women who had cervical cancer. The frequency of orgasms and orgasmic pleasure was similar in the two groups. Among the women who had cervical cancer, the type of treatment received had little if any effect on the prevalence of specific vaginal changes. CONCLUSIONS: Women who have been treated for cervical cancer have persistent vaginal changes that compromise sexual activity and result in considerable distress.

Adult↗

PubMed1999

Dietary heterocyclic amines and cancer of the colon, rectum, bladder, and kidney: a population-based study.

BACKGROUND: Heterocyclic amines formed in cooked meat and fish are carcinogenic in animal models and form DNA adducts in human beings. We undertook a study to assess whether these substances are related to the risks of cancer in the large bowel and urinary tract. METHODS: In a population-based case-control study, cases were identified from the Swedish cancer registry. Controls were randomly selected from the population register. Information on intake of various foods and nutrients was assessed by questionnaire, with photographs of foods cooked at various temperatures. We measured the content of heterocyclic amines in foods cooked under these conditions. FINDINGS: Information was retrieved from 553 controls, 352 cases of colon cancer, 249 cases of rectal cancer, 273 cases of bladder cancer, and 138 cases of kidney cancer. The response rate was 80% for controls and 70% for cases. The estimated daily median intake of heterocyclic amines was 77 ng for controls, and 66 ng, 63 ng, 96 ng, and 84 ng for cases with cancer of the colon, rectum, bladder, and kidney, respectively. The relative risk for the intake of heterocyclic amines (highest vs lowest quintile) was 0.6 (95% CI 0.4-1.0) for colon cancer, 0.7 (0.4-1.1) for rectal cancer, 1.2 (0.7-2.1) for bladder cancer, and 1.0 (0.5-1.9) for kidney cancer. Seven cases, but no controls, had an estimated daily intake of heterocyclic amines above 1900 ng. INTERPRETATION: Intake of heterocyclic amines, within the usual dietary range in this study population, is unlikely to increase the incidence of cancer in the colon, rectum, bladder, or kidney. For daily intakes above 1900 ng, our data are consistent with human carcinogenicity, but the precision was extremely low.

Aged↗

PubMed1999

A population-based dietary inventory of cooked meat and assessment of the daily intake of food mutagens.

Frequent consumption of meat has been associated with an increased risk of colorectal cancer. Such a risk may be due to naturally occurring compounds in the meat, substances added to the meat, or agents formed during cooking. Concerning the latter alternative, mutagenic heterocyclic amines are multi-site animal carcinogens, but their relevance to human cancer has yet to be determined. In the present study, we made a population-based inventory of cooked meat dishes consumed in the county of Stockholm, ranked dishes according to cooking method and frequency of consumption and, in addition, determined levels of mutagenic activity in six commonly consumed fried meat dishes. Meat was consumed, on average, 493 times per year, giving 1.4 daily servings. Frying was the most common way to cook meat. When ranking meat dishes according to intake frequency, the top eight dishes were as follows: sausage, steak casserole, meatballs, pork chops, pork belly, bacon, ground beef patties, and finally, mince-meat sauce. The frying sessions were performed under controlled conditions at four different temperatures, and we documented the degree of surface browning and measured mutagenic activity in six frequently eaten dishes (sausage, meatballs, pork chops, pork belly, ground beef patties, and minute beef). We found extracts from all six dishes to be mutagenic, and a mean daily dose of exposure was calculated, giving 862 revertants. This investigation leaves no doubt that a major portion of the total meat consumption is fried before ingestion and that fried meat dishes frequently consumed by an elderly population in Stockholm contain mutagenic substances. Furthermore, the study provides usable information for future epidemiological research in which it is necessary to disentangle the effect of meat per se from the effect of potentially carcinogenic heterocyclic amines.

Aged↗

PubMed1999

Measuring errors and non-participation in a nation-wide study of stillbirth.

BACKGROUND: An observational study in which data are being collected by an anonymous questionnaire is an alternative when an intervention cannot be investigated by a controlled clinical trial. If used, measuring errors and non-participation may decrease validity. METHODS: We compared data retrieved with an anonymous questionnaire in a nation-wide study on stillbirth with information from the Swedish Medical Birth Register. In the original study population with 759 women, four groups were formed comprising participants and non-participants among subjects (stillbirth in 1991) and controls (live birth the same year). To assess misclassification, we compared information provided by the questionnaire to the data for the corresponding group in the Swedish Medical Birth Register. Comparing background information on participants and non-participants elucidated misrepresentation. RESULTS: The figures from the questionnaire and the register were almost identical for hypertension, albumin and sugar in the urine during pregnancy, while anemia and tiredness were reported more often in the questionnaire. Similar results were found in the two data sources regarding the type and frequency of analgesia during the delivery, birth order, gender and weight of the index child. On average, all women reported a larger number of gestation weeks in the questionnaire than was indicated in the register-based information. A higher percentage of the participants than the non-participants, both among subjects and controls, were born in Sweden, had Swedish citizenship and were married or cohabiting. CONCLUSION: Information on many variables derived from an anonymous questionnaire can be used in a scientific context. The validity of a study in the investigated population would probably be enhanced if it were restricted to subjects born in Sweden.

Analysis of Variance↗

PubMed1999

Assessing the human intake of heterocyclic amines: limited loss of information using reduced sets of questions.

The aim of this study was to evaluate loss of information from a reduced food frequency questionnaire as compared with an extensive reference method developed to assess the intake of heterocyclic amines (HCAs). Food frequency data were linked to concentrations of HCAs in cooked foods to estimate the individual daily exposure to a combination of five HCAs. The number of food items in the questionnaire was reduced and selected in three ways: (a) according to the contribution to the estimated total intake; (b) the between-person variance; or (c) dishes included in other studies. The effect on sensitivity, specificity, concordance, the correlation coefficient, kappa, and simulated relative risks was determined using information from a population-based study conducted in Stockholm. Only a limited amount of misclassification was introduced when the number of dishes was reduced from 39 to 15 or 20, and no major difference was seen when dishes were selected according to the total intake or the between-person variance. Our data indicate that for a specific exposure, such as HCAs, the loss of accuracy in an analytical epidemiological study is small and may not be relevant when the number of dishes in a food frequency questionnaire is decreased, if the initially chosen dishes are carefully selected and cover a reasonable part of the total intake or between-person variance.

Aged↗

PubMed1999

Deferred treatment of locally advanced nonmetastatic prostate cancer: a long-term followup.

PURPOSE: We prospectively investigated long-term survival in select men with locally advanced, nonmetastatic prostate cancer managed with deferred treatment. MATERIALS AND METHODS: A total of 50 patients with prostate cancer clinically outside the prostatic capsule and without distant metastases were included in a surveillance protocol. The men were treated if and when symptoms occurred or upon request. The series was followed until December 1994. No patient was lost to followup. RESULTS: Median patient age at diagnosis was 71 years. All patients were followed more than 144 months or died before then. Actual (cumulative incidence) overall and disease specific survival rates at 5, 10 and 12 years were 68 and 90, 34 and 74, and 26 and 70%, respectively. A third of the patients had not received antitumor treatment at followup or before death. CONCLUSIONS: When managed with deferred treatment nonpoorly differentiated, locally advanced nonmetastatic prostate cancer seems to have a poorer survival outcome than similarly managed clinically localized prostate cancer. However, compared with other treatments and in terms of survival deferred treatment may be an option for select patients with such tumors and a life expectancy of 10 years or less.

Aged↗

PubMed1998

A comparison of women's memories of care during pregnancy, labour and delivery after stillbirth or live birth.

OBJECTIVE: To compare women's reports of aspects of their care during pregnancy, labour and delivery following stillbirth and live birth. DESIGN: Data were collected by postal questionnaire in 1994. SETTING: A Swedish nation-wide population-based study of cohorts defined in 1991. PARTICIPANTS: Three hundred and fourteen women with stillbirth (subjects) and 322 women with live birth (controls). MEASUREMENTS AND FINDINGS: Labour and delivery were assessed as physically 'insufferably hard' by 52 (17%) of the subjects and 33 (10%) of the controls. The corresponding figures for emotional strains were 144 (47%) and 21 (7%). Obstetric analgesia was more frequently used during labour for stillbirth. One hundred and thirty-eight (44%) subjects, as compared to 44 (2%) of the controls, left hospital within 24 hours of birth. Almost all the women with stillbirth 296 (95%) stated that it was important to have an explanation of the baby's death. Adverse events related to bromocriptine given to inhibit postpartum lactation, were reported by 60 (22%) of the subjects. KEY CONCLUSIONS: It is possible to ease the distress of labour and delivery for stillbirth. Discussion of the aetiology of the baby's death with the mother should be a priority. The optimal length of stay in hospital after stillbirth remains to be defined. Non-pharmacological inhibition of lactation may be presented as an alternative to bromocriptine, breast binding is a concrete 'reality confrontation' for the woman and may aid her in her grieving process. Further studies concerning breast binding vs pharmacological inhibition of lactation and long-term psychological outcome are warranted.

Adult↗

PubMed1998

Distress due to unwanted side-effects of prostate cancer treatment is related to impaired well-being (quality of life).

Based on traditional quality of life scales, it has been suggested that known side-effects of prostate cancer treatment do not influence the quality of life. The present authors have developed an alternative approach to quality of life assessment applying epidemiological methods. Using a self administered questionnaire, we investigated 431 prostate cancer patients and an age stratified sample of 435 randomly selected men. Patients reporting any level of distress due to waning sexual functions (66%) or urine or bowel symptoms (38%), reported a lower psychological well-being compared to patients not reporting these symptoms or patients not distressed by their symptoms. Our results stress that an intact sexual and urinary and bowel functions are important for the quality of life among elderly men with or without prostate cancer.

Journal Article↗

PubMed1998

'Potency': the validation of information from a self-administered questionnaire using objective measurements of night-time erections and test-retest reliability.

OBJECTIVE: To assess the validity and reliability of a questionnaire assessing 'physiological potency'. PATIENTS AND METHODS: The study comprised 89 patients with prostate cancer and 43 men without; the latter were attending a consultation clinic because of problems with erection. All men answered three questions assessing erectile rigidity during sexual activity, morning and spontaneous erections. In the questionnaire, 'potency' was defined as erectile rigidity 'sufficient for intercourse most of the time' or better. 'Potency' in one or more of the three aspects of erection was defined as 'physiological potency'. The patients with prostate cancer answered the questionnaire twice with a 3-week interval. The men attending the consultation clinic underwent two nights of erectile monitoring (using the RigiScan device) and the minimum criterion for RigiScan potency was defined as 55% rigidity at both tip and base. RESULTS: The test-retest assessment showed 93% conformity in the questionnaire diagnosis of 'physiological potency/impotence' between the tests. The sensitivity and specificity of the questionnaire assessment compared with the RigiScan method were 40% and 100%, respectively, when the question assessing sexually stimulated erectile rigidity was used alone. Using 'physiological potency', the sensitivity increased to about 60% without jeopardizing the specificity, and when men reporting depression were excluded from the analysis, the sensitivity increased to about 80%. CONCLUSIONS: The test-retest reliability of the questionnaire was satisfactory. Using questions in a self-administered questionnaire, 'physiological impotence' can be diagnosed with complete and 'physiological potency' with 60-80% sensitivity. The sensitivity of the self-assessment for 'potency' depended on the number of questions asked and the proportion of men reporting depression.

Erectile Dysfunction↗

PubMed1998

A comprehensive clinical epidemiological theory based on the concept of the source person-time and four distinct study stages.

The medical community is forced to accelerate the move from opinion-based to evidence-based medicine, that is, to aim at basing all caring and clinical practice on empiri. A clear-cut epistemology would facilitate this process. In this article we present a comprehensive clinical epidemiological theory which can be used for validity issues in caring science, quality of life research, controlled clinical trials and compilations of uncontrolled evidence. The theory is based on four distinct stages that can be identified in a study, whereof the first is demarcation of the source person-time. A source person-time ('study base') can be identified for any study in all disciplines, giving an argument for using this concept as the common reference point for validity issues. Apart from identifying the source person-time, recovery of the actually observed person-time, collection of data and calculation of an ('adjusted') effect parameter (e.g., incidence ratio) are additional stages of a study. When the source person-time is demarcated confounding is introduced, when the actually observed person-time is recovered misrepresentation, in the third stage misclassification and in the fourth analytical alteration of the parameter of effect. The concept of the source person-time can, in addition, link examination of validity in caring and clinical sciences to observational studies, thereby allowing the field to benefit from all theoretical achievements for preventing, handling and understanding systematic errors developed in epidemiology. We conclude it is possible to implement a common terminology of validity for all caring and medical sciences. Drawing causal inferences in these disciplines is not mechanical, it can never, for example, be done with statistical inference. Establishing a causal relation always includes an assessment of the magnitude and direction of systematic errors influencing the adjusted effect parameter. From the presented epistemology it follows that differences in validity from a case history to a large randomized, placebo-controlled and double-blinded study are quantitative rather than qualitative. This realization in turn opens up for a more refined discussion of when a decision is evidence-based rather than opinion-based.

Clinical Trials as Topic↗

PubMed1998

Urinary and bowel symptoms in men with and without prostate cancer: results from an observational study in the Stockholm area.

OBJECTIVES: To investigate the prevalence of urinary and bowel symptoms in population-based groups of men with and without prostate cancer. METHODS: A self-administered questionnaire, assessing 5 urinary and 3 bowel symptoms, was sent to the 431 men diagnosed as having prostate cancer in the Stockholm area in 1992 who were still alive in October 1993 and to 435 randomly selected control subjects with an age distribution matching men with newly diagnosed prostate cancer in the same area. The results were evaluated as ratios of proportions. RESULTS: Among the prostate cancer patients, all urinary and bowel symptoms assessed were more common and the risk of having the various symptoms was 1.3-4.5 times that of the controls. The risks of having leakage of urine after radical prostatectomy and bowel urgency after external beam radiation therapy were fourfold when compared with the control group. We noted an increased risk ratio of proportions of leakage of faeces after radical prostatectomy and this risk was significantly increased when men with any of 11 specified diseases were excluded from the analysis to reduce confounding. CONCLUSIONS: Prostate cancer and its treatment affects urinary and bowel functions. The increased risk of having leakage of faeces after radical prostatectomy may be a chance phenomenon due to few patients subjected to surgery, but warrants further investigation.

Aged↗

PubMed1997

Prostate carcinoma and long term survival.

BACKGROUND: The long term survival of patients with prostate carcinoma is not well understood. The objective of the current study was to investigate the temporal trend of prostate carcinoma mortality in patients who survived > or = 10 years after diagnosis. METHODS: Men with prostate carcinoma diagnosed from 1958 through 1983 in the Stockholm/Gotland region in Sweden and who survived > or = 10 years after the diagnosis were investigated regarding survival beyond 10 years. The expected survival was calculated from an annually selected age and time-matched cohort of men from the general population in the same geographic region. The relative survival was expressed as the annual quotient of the observed survival over the expected survival. RESULTS: The authors identified 1896 patients who had survived > or = 10 years. The relative survival decreased up to approximately 18 years after the diagnosis, whereupon it reached a plateau that was constant up to 30 years after diagnosis. CONCLUSIONS: Men with prostate carcinoma surviving > or = 10 years have an excess mortality compared with age-matched controls. This excess mortality ceases 20 to 23 years after diagnosis and the observed and the expected survival are similar, indicating few, if any, deaths from prostate carcinoma from there on.

Aged↗

PubMed1997

Supplementary iron intake and risk of cancer: reversed causality?

Dietary iron intake and body iron stores have been suggested to increase cancer risk, especially colorectal cancer. Within a population-based case-control study in Stockholm county 1993-94, information on dietary and supplementary iron intake were collected through a food frequency questionnaire. An initially noted positive association between intake of supplementary iron and colorectal cancer risk was reversed when intake 5 years prior to cancer diagnosis was subtracted. Reversed causality due to early disease giving symptoms of iron shortage, resulting in iron supplementation, is an issue to consider when a possible association between intake of iron and cancer risk is investigated.

Age Factors↗