PubMed Health⌕ Search

Biomedical subjects

J Adolfsson

Publications and source records attributed to J Adolfsson.

At least 37 records · Page 2Linked to original sources
PubMed2000

Localized prostate cancer and 30 years of follow-up in a population-based setting.

Some patients with a histopathological diagnosis of prostate cancer have a tumour that behaves benignly during long-term follow-up. The proportion of patients with such a tumour is unknown, as is the fraction who die of prostate cancer between 10 and 20 y of follow-up. All men aged 45-84 y obtaining a diagnosis of prostate cancer between 1965 and 1993 and being reported to the Finnish Cancer Registry were observed. Death was recorded as caused by prostate cancer or not. We identified 11,500 men with localized prostate cancer and in this group the disease-specific survival rate reached a plateau at approximately 30% after 23 y of follow-up. In the same cohort, 5% of the patients died of prostate cancer during years 11-20 of follow-up. During the observation period, somewhat less than half of the patients with localized prostate cancer who died, died of the disease. This proportion decreased with duration of follow-up. In conclusion, early aggressive therapy for localized prostate cancer is unnecessary, in terms of survival, for those with a benignly behaving tumour (about 30% in this series) or who die of intercurrent disease (about 50% in this series). Such therapy may, however, prolong life for the patients and may cure the patients that die of prostate cancer after more than 10 y follow-up. Prostate Cancer and Prostatic Diseases (2000) 3, 37-42

Journal Article↗
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

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↗
PubMed2000

Clinical management of premalignant lesions of the prostate. WHO Collaborative Project and Consensus Conference on Public Health and Clinical Significance of Premalignant Alterations in the Genitourinary Tract.

The presence of high-grade prostatic intraepithelial neoplasia (PIN) in a prostate biopsy is a considerable risk factor for the presence of prostate cancer, with up to 73% of patients having cancer on rebiopsy. The risk is related to the clinical setting (screening vs urological practice) and patient factors such as prostatic serum antigen (PSA) and findings on digital rectal examination (DRE). Thus, high-grade PIN has serious clinical implications. The aim of this paper is to propose practical guidelines for the clinical management of PIN. Based on current knowledge we recommend that: Only patients considered for curative treatment of prostate cancer be further investigated for a PIN biopsy finding; A palpable nodule or tumor-suspicious transrectal ultrasonography (TRUS) finding, in conjunction with a finding of high-grade PIN on prostate biopsy, should prompt rebiopsy; An elevated PSA level or an elevated PSA density should also warrant repeat biopsy, as the most likely cause of PSA elevation is concomitant prostate cancer; The presence of high-grade PIN on biopsy without concomitant prostate cancer in patients suitable for curative treatment, notwithstanding normal DRE, TRUS or PSA, should prompt repeat biopsies, as the association with prostate cancer is significant; The presence of PIN alone on biopsy does not warrant treatment, as a substantial number of rebiopsies yield only PIN.

Biopsy↗
PubMed1999

Lymphoid-restricted development from multipotent candidate murine stem cells: distinct and complimentary functions of the c-kit and flt3-ligands.

The two tyrosine kinase receptors, c-kit and flt3, and their respective ligands KL and FL, have been demonstrated to play key and nonredundant roles in regulating the earliest events in hematopoiesis. However, their precise roles and potential interactions in promoting early lymphoid commitment and development remain unclear. Here we show that most if not all murine Lin(-/lo)Sca1(+)c-kit(+) bone marrow (BM) cells generating B220(+)CD19(+) proB-cells in response to FL and interleukin-7 (IL-7) also have a myeloid potential. In contrast to FL + IL-7, KL + IL-7 could not promote proB-cell formation from Lin(-/lo)Sca1(+)c-kit(+) cells. However, KL potently enhanced FL + IL-7-stimulated proB-cell formation, in part through enhanced recruitment of FL + IL-7-unresponsive Lin(-/lo)Sca1(+)c-kit(+) progenitors, and in part by enhancing the growth of proB-cells. The enhanced recruitment (4-fold) in response to KL occurred exclusively from the Lin(-/lo)Sca1(+)c-kit(+)flt3(-) long-term repopulating stem cell population, whereas KL had no effect on FL + IL-7-stimulated recruitment of Lin(-/lo)Sca1(+)c-kit(+)flt3(+) short-term repopulating cells. The progeny of FL + IL-7-stimulated Lin(-/lo)Sca1(+)c-kit(+) cells lacked in vitro and in vivo myeloid potential, but efficiently reconstituted both B and T lymphopoiesis. In agreement with this FL, but not KL, efficiently induced expression of B220 and IL-7 receptor-alpha on Lin(-/lo)Sca1(+)c-kit(+)flt3(+) cells. Thus, whereas KL appears crucial for recruitment of FL + IL-7-unresponsive candidate (c-kit(+)flt3(-)) murine stem cells, FL is essential and sufficient for development toward lymphoid restricted progenitors from a population of (c-kit(+)flt3(+)) multipotent short-term reconstituting progenitors.

Animals↗
PubMed1999

Diagnostic value of percent free prostate-specific antigen: retrospective analysis of a population-based screening study with emphasis on men with PSA levels less than 3.0 ng/mL.

OBJECTIVES: To retrospectively investigate the use of percent free prostate-specific antigen (PSA) compared with total PSA in serum as predictor of prostate cancer in men selected randomly from the general population who underwent biopsy on the basis of abnormal findings on digital rectal examination (DRE) or transrectal ultrasound (TRUS) and/or serum PSA levels greater than 10 ng/mL. METHODS: A single intervention, population-based screening study was undertaken in 1988 and 1989. Of the 2400 men aged 55 to 70 years invited to participate, 1782 men responded and were examined with DRE, TRUS, and PSA testing (Tandem-Hybritech). In 1995, frozen serum samples from 1748 men were analyzed for percent free PSA (Prostatus, Wallac OY). Five-year follow-up data on new cancers in the screened population were obtained from the Swedish Cancer Registry (SCR). RESULTS: Of the 1748 men, 367 underwent TRUS-guided biopsies because of abnormal findings on either DRE or TRUS or serum PSA levels of greater than 10 ng/mL. This resulted in the diagnosis of 64 cases of prostate cancer (3.7%). PSA levels of 3.0 ng/mL or greater were found in 55 (86%) of 64 cancer cases and in 399 (24%) of the 1684 benign cases. Among the 1294 men with PSA less than 3.0 ng/mL, 9 prostate cancers were diagnosed (14% of all prostate cancers). All 9 patients with cancer and with PSA less than 3.0 ng/mL had a percent free PSA of 18% or less. In the group of 1109 patients with PSA less than 3.0 ng/mL and a percent free PSA greater than 18%, 159 biopsies were performed because of abnormal DRE or TRUS. However, no prostate cancer was diagnosed in this category of patients. Five years after the screening intervention, 7 more cases of prostate cancer were clinically diagnosed in the screened population according to the SCR. CONCLUSIONS: The combination of PSA levels less than 3.0 ng/mL and percent free PSA greater than 18% defines a large part of the population at a very low risk of cancer of the prostate both at the time of screening and during the following 5 years. Men in this group may be spared DRE, and longer screening intervals may be considered. However, the risk of having prostate cancer is not negligible in men with PSA less than 3.0 ng/mL and percent free PSA of 18% or less. The results of this study indicate that biopsy should be recommended to men fulfilling these criteria, although these results should be confirmed in larger prospective studies because of the limited number of patients with prostate cancer in the present series.

Aged↗
PubMed1999

Endogenously formed nitric oxide modulates cell growth in bladder cancer cell lines.

OBJECTIVES: Nitric oxide (NO) is formed in many mammalian tissues, and a growing body of evidence suggests that NO is involved in cell growth and cell differentiation. Low concentrations of NO can stimulate cell growth; high concentrations result in cytostatic/cytotoxic effects. It has previously been shown that intravesical treatment with bacille Calmette-Guérin (BCG) for bladder cancer increases NO production in the human urinary bladder and that NO inhibits bladder cancer cell growth in vitro. In this study, we investigated nitric oxide synthase (NOS) activity in different bladder cancer cells and the role of the NO precursor L-arginine in cell proliferation. METHODS: NOS activity was assessed by citrulline assay in cultured normal human urothelial cells and bladder cancer cell lines T24 and MBT-2 before and after treatment with cytokines. We also measured cell growth at various L-arginine concentrations and after addition of the NOS inhibitor N(G)-nitro-L-arginine (L-NNA) in unstimulated and cytokine-stimulated cells. RESULTS: Normal urothelial cells, as well as T24 and MBT-2 cells, showed calcium-dependent NOS activity under basal conditions. The bladder cancer cell lines also showed calcium-independent NOS activity in contrast to the normal cells. After cytokine treatment, both the normal cells and the cancer cell lines showed a marked increase in calcium-independent NOS activity. There was a dose-dependent stimulation of cell growth in the cancer cell lines after L-arginine addition, and this effect could be antagonized by L-NNA. Cytokine treatment inhibited cell growth, and this inhibition was partly reversed by L-NNA. CONCLUSIONS: Normal urothelial cells and bladder cancer cell lines MBT-2 and T24 show NOS activity, and cytokine treatment induces calcium-independent NOS activity. Our results suggest that endogenous activity of the constitutively expressed form of NOS in unstimulated cells promotes cell proliferation, and NO production secondary to increased activity of the inducible form of NOS after cytokine treatment inhibits cell growth.

Arginine↗
PubMed1999

The natural history of early prostate cancer and the impact of endocrine treatment.

The best approximation of the natural course of early prostate cancer comes from studies on deferred treatment. In such studies, the 10-year disease-specific survival rate is 85-90% for patients with clinically localized tumours and 74% for those with tumours not confined to the prostate gland; 15-year data are sparse and diverging. Patients with poorly differentiated tumours have a worse prognosis than those with well or moderately differentiated tumours. Endocrine treatment of early prostate cancer is a revitalized concept, with the majority of the evidence for a beneficial effect coming from uncontrolled studies. Recently, however, data from two randomized studies have suggested that endocrine treatment may prolong survival in patients with non-metastatic prostate cancer. Also, in studies of radiotherapy for localized prostate cancer, a longer survival has been seen in patients randomized to neoadjuvant or adjuvant endocrine treatment compared with placebo. The current trend for earlier treatment means that the total time on endocrine therapy has increased and patients are younger when treatment is initiated. Therefore, randomized studies should not only substantiate a possible survival benefit of endocrine treatment, but also assess potential long-term side effects and their impact on quality of life.

Antineoplastic Agents, Hormonal↗
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

Effects of L-arginine treatment on symptoms and bladder nitric oxide levels in patients with interstitial cystitis.

OBJECTIVES: Nitric oxide (NO) is involved in host defense reactions, and NO production is elevated in various inflammatory disorders. We have found very high levels of luminal NO in the urinary bladder of patients with interstitial cystitis. Oral treatment with low doses of L-arginine, the substrate for NO production, has been reported to alleviate symptoms in patients with interstitial cystitis. The aim of our investigation was to evaluate the effect of higher doses of L-arginine in patients with interstitial cystitis and to study the effects of L-arginine on NO production in the bladder. METHODS: Nine women (age 69+/-3 years) with interstitial cystitis were treated daily with 3 or 10 g of L-arginine for 5 weeks. Symptoms were evaluated with an interstitial cystitis symptom score index, and NO production was measured. Patients with stress incontinence (n=18) were used as control subjects for measurement of NO levels. RESULTS: NO concentration in the urinary bladder was markedly elevated in the patients with interstitial cystitis (239+/-60 ppb) compared with the control patients (15+/-2 ppb). NO levels did not change in the patients with interstitial cystitis after oral treatment with L-arginine (189+/-72 ppb). There was no significant change in the symptom scores at either dose after 5 weeks of L-arginine treatment. CONCLUSIONS: L-arginine treatment in the doses used in this study did not change NO production in the urinary bladder in patients with interstitial cystitis. Furthermore, the patients in our study did not notice any relief of their symptoms.

Aged↗
PubMed1998

The role of nitric oxide in bacillus Calmette-Guérin mediated anti-tumour effects in human bladder cancer.

Bacillus Calmette-Guérin (BCG) has been used for many years to treat cancer of the urinary bladder. It constitutes effective intravesical therapy of carcinoma in situ and recurrent superficial bladder cancer. Although the mechanism of action is unknown, most evidence suggests an immune-mediated mechanism. BCG treatment is known to increase cytokine production in the urinary bladder. As cytokines may induce nitric oxide synthase (NOS) activity and as nitric oxide (NO) exerts cytotoxic effects on tumour cells, we investigated the role of NO in BCG-mediated anti-tumour activity. Here we demonstrate a marked induction of both calcium-dependent and calcium-independent NOS activity in the human urinary bladder after BCG treatment. The presence of NOS in the urothelial cells was also demonstrated by the use of immunohistochemistry. Furthermore, patients treated with BCG showed a 30 times higher production of gaseous NO as measured in the urinary bladder by chemiluminescence. Finally, NO donors exerted cytotoxic effects on bladder cancer cell lines. These findings suggest that NO synthesis may be an important mechanism in BCG-mediated anti-tumour therapy.

BCG Vaccine↗
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

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↗
PubMed1998

Sexual dysfunction associated with the management of prostate cancer.

Improvements in the management of prostate cancer have increased the need to consider patients' quality of life, in particular in relation to sexual function. The causes of sexual dysfunction are varied and derive from both the condition and its management. Health professionals must choose their treatment strategies with great care. Patient expectations must be understood, and patients should be offered counselling, as an understanding of what can reasonably be expected contributes to patients' perception of their quality of life. There are few studies on sexual dysfunction in patients with prostate cancer. A first step would be to develop reliable questionnaires for the assessment of the problem. This article describes and discusses the findings of one such recently developed questionnaire. When baseline measures of sexual function have been established and the extent of sexual dysfunction in patients with prostate cancer is reliably quantified, large multicentre trials can be performed to evaluate the impact of different therapies on sexual function and quality of life. Sexual dysfunction is an area which will be of increasing importance to urologists who manage prostate cancer and one that should not be underestimated.

Aged↗
PubMed1998

Nitric oxide synthase activity in human renal cell carcinoma.

PURPOSE: Nitric oxide (NO) is generated in mammalian tissue by the conversion of L-arginine to L-citrulline. The reaction is catalyzed by nitric oxide synthase (NOS). NO has been suggested to have a dual role in tumor biology with both antitumor and tumor promoter activity. Furthermore, it has been proposed that NO contributes to interleukin-2-induced antitumor activity. Since interleukin-2 is used in the treatment of renal cell carcinoma (RCC) it was of interest to study the NOS activity in the human kidney and in RCC and its correlation to tumor grade. Furthermore, the effect of cytokine treatment on NOS activity and the effect of NO donor application was studied in cultured cells. MATERIALS AND METHODS: The effect of cytokine treatment on NOS activity and the effect of NO donor application on cell proliferation was studied in cultured human proximal tubular cells and in RCC cell lines HN4 and HN51. NOS activity was measured by the L-arginine to L-citrulline conversion assay. RESULTS: Calcium-dependent NOS activity was found in all non-malignant kidney tissues (486+/-63 pmol. min(-1) g(-1) tissue). The activity was significantly lower in RCC (24+/-6 pmol. min(-1) g(-1) tissue) and correlated with tumor grade; thus high grade tumors showed lower activity than low grade tumors. Calcium-independent NOS activity was not detected in non-malignant kidney tissue or in RCC tissue. In cultured proximal tubular cells and RCC cell lines HN4 and HN51, cytokine treatment induced a marked increase in NOS activity and NO exerted cytostatic effects on these cell lines. CONCLUSIONS: The NOS activity was higher in non-malignant kidney tissue than in RCC tissue and was inversely correlated with tumor grade. Furthermore, cytokine treatment induced a marked increase in NOS activity and NO exerted cytostatic effects on cultured proximal tubular cells and RCC cell lines.

Analysis of Variance↗
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↗