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Biomedical subjects

E Varenhorst

Publications and source records attributed to E Varenhorst.

At least 19 recordsLinked to original sources

Comparison of an LH-RH analogue (Goeserelin acetate, 'Zoladex') with combined androgen blockade in advanced prostate cancer: final survival results of an international multicentre randomized-trial. International Prostate Cancer Study Group.

OBJECTIVE: The aim of this study was to compare the effects of the nonsteroidal antiandrogen flutamide plus the LH-RH analogue goserelin acetate (combined androgen blockade [CAB]) with goserelin acetate alone in patients with advanced prostate cancer. The original analyses at 25 and 56 months of follow-up have been reported previously, and here we report the final survival analysis after 10 years of follow-up. METHODS: 589 patients with advanced prostate cancer (55% with metastatic [M1] and 45% with locally advanced [M0] disease) were randomized to receive goserelin acetate 3.6 mg either alone or in combination with flutamide (250 mg three times daily). RESULTS: A total of 583 patients were included in the analysis. There was a small, but nonsignificant, benefit for CAB compared with goserelin acetate alone in all patients with respect to survival (hazard ratio 0.88, 95% CI 0.73, 1.06). Subgroup analysis of M0 and M1 patients showed similar results (M0: hazard ratio 0.92, 95% CI 0.68, 1.25; M1: hazard ratio 0.85, 95% CI 0.66, 1. 08). The treatment effect was not significantly different for M0 and M1 patients (p = 0.685). CONCLUSIONS: In this large randomized trial containing significant numbers of M0 patients, after 10 years there was a small but nonsignificant benefit for CAB over castration alone.

Aged

[Microscopic hematuria in adults--a diagnostic dilemma. Scientific guidelines for management are not available according to a review of the literature].

Red cell urinalysis is a very common laboratory procedure in health care, and microscopic haematuria a common finding in apparently healthy people. Response to a questionnaire sent to all departments of urology in Sweden and to general practitioners in the province of Ostergötland showed both groups to vary considerably in their approach to its management. Accordingly, to determine whether a reliable scientific basis exists for its management, a literature search for the period, 1975-97, was made in MEDLINE, under the headings haematuria, microscopic haematuria and microhaematuria, which yielded a total of 845 items. After scrutiny of the abstracts, 203 reports were selected for closer study in the following respects: study design, series studied, selection criteria, age and gender distribution, test methods used, cut-off values for further investigation, and study results. In 17 series comprising a total of 5,000 patients, urological cancer was diagnosed in less than three per cent of cases. Of almost 200,000 males and females patients tested for haematuria, less than one per cent were found to have disease requiring treatment. In general, the studies were characterised by an absence of control groups, and by differences in study design, selection criteria, test methods, definitions of microscopic haematuria, and investigatory procedures. There were no randomised prospective studies where patients undergoing investigation were compared with those undergoing follow-up only. Thus, as available documentation in professional journals and textbooks shows no consensus to exist as to management in cases of microscopic haematuria, further research is required in this field before scientifically sound guidelines can be issued.

Adult

The role of arterial embolization in renal cell carcinoma.

Twenty-five years ago arterial embolization was introduced to facilitate the surgical excision of the carcinomatous kidney or to palliate symptoms, such as haemorrhage from non-resectable tumours. The role of this technique in the therapeutic armamentarium has been a source of debate in the literature. We reviewed all the available literature. A total of 389 papers were evaluated. Fifty-one publications and 3225 case histories met explicit entry criteria for inclusion. Until now no prospective randomized study of this approach to the management of renal carcinoma has been published. In the majority of studies the patients are grouped together irrespective of indication, i.e. pre-operative or palliative. Few articles are prospective or contain clear information regarding tumour stage, indication and adequate follow-up. Although we are not able to distinguish with certainty the effect of embolization on the course of the disease, it seems that complete pre-operative renal artery embolization facilitates the excision of large vein-invading tumours. The optimal delay between embolization and operation is probably one day. The embolization material of choice is ethanol. Palliative embolization in non-operable tumours with serious haemorrhage seems to have been successful in most cases. The scientific basis for the implementation of renal artery embolization in renal cell carcinoma is weak. We believe that either controlled trials or parallel prospective cohort studies should be undertaken to compare treatment of selected locally advanced renal carcinomas with and without embolization.

Carcinoma, Renal Cell

Prostate cancer registration in four Swedish regions 1996-- differences in incidence, age structure and management.

INTRODUCTION: In 1996 registration of prostate cancer in four of the six Swedish regions was started to facilitate evaluation of geographical variations in incidence and treatment. MATERIAL AND METHODS: For all cases of prostate cancer, personal identification number, tumour stage, tumour grade and primary treatment were registered. RESULTS: In the four regions covered by the register, 3541 cases of prostate cancer were registered. Altogether there were 5795 cases of prostate cancer diagnosed in Sweden the same year. The age-standardized incidence varied from 89/100000 to 169/100000 among counties. The proportion of localized tumours correlated positively to the incidence (p < 0.05) and negatively to mean age at diagnosis (p < 0.01). There was also a significant positive correlation between the proportion of localized tumours and the percentage of patients given curative treatment. All registered variables showed large geographical variations, especially concerning percentage of T1c tumours, treatment of localized tumours and choice of palliative treatment. CONCLUSION: Diagnostic activity varied considerably among counties, resulting in large variation in age-standardized incidence. High incidence is associated with a larger proportion of localized tumours, which, in turn, is associated with early age at diagnosis. In counties where a policy of detecting tumours early is practised, curative treatment is also given more often. Treatment of localized tumours and preference for palliative treatment seem to depend on local traditions. The lack of cytological and histopathological standards makes geographical comparisons based on tumour grade impossible.

Age Distribution

Economic evaluation of screening for prostate cancer: a randomized population based programme during a 10-year period in Sweden.

Prostate cancer is a growing health problem representing considerable costs. Screening and early curative treatment may reduce morbidity and possibly prevent future escalating costs. However, population screening programmes are generally not well accepted at present due to uncertainty about whether screening for prostate cancer can result in reduced mortality. Evidence from large, randomized, controlled trials is still lacking. The objective of this study was to calculate clinical and economic consequences of general prostate cancer screening based on a limited screening trial in a Swedish community and a decision-tree model. A random selection of 1492 men (50-69 years) were invited to repeated screening in 1987. They have been examined every third year (four rounds). The other 7679 men in the population act as controls. The results show that the total incremental health care costs for prostate cancer will increase by 179 million SEK per year with screening compared to no-screening. The number of detected cases of localized cancer will increase by about 1000, which represents an additional cost of about 158,000 SEK per case. In conclusion, general screening for prostate cancer can be performed with a reasonable cost per detected localized cancer. Information on the long-term effect on life quality and cancer mortality is unknown.

Aged

Impact on health service costs of medical technologies used in management of prostatic cancer.

The aim of the study was to calculate the direct costs for the management of prostatic cancer throughout the need for care period. The impact of new medical technologies was analysed on the basis of an earlier cost study. The records of all 128 men in a defined population who died in 1992-93 and had been diagnosed with prostatic adenocarcinoma were retrospectively reviewed from diagnosis to death. The median cost per case, SEK 86,400, was significantly lower than the average cost per case, SEK 135,000, largely because of a few high-cost patients (in 20% of cases the cost exceeded SEK 250,000). Analysis of cost distribution throughout the need for care period showed that about 84% of the total cost per case was incurred during the the 3 years up to death. Estimated total direct care costs due to prostatic cancer in Sweden in the mid-1980s and early 1990s rose from approx. SEK 550 million to approx. SEK 780 million (1993 prices).

Adenocarcinoma

[Decreasing number of orchiectomies in prostatic cancer. Results of 9-year registration of the disease are reviewed].

There are several controversies regarding the management of prostate cancer. Whether curative treatment (e.g. radiotherapy and total prostatectomy) prolongs survival remains uncertain. Conservative management is beset with such unresolved issues as the effect on tumour progression of early instituted hormonal treatment and of treatment deferral. Since the outcome of the different types of treatment is unclear the value of screening and early detection remains uncertain. Owing to such issues as these, and the divergent views on prostate cancer, there is an urgent need of auditing. To co-ordinate prostate cancer care in the South-east Region of Sweden, a local management programme with principles for investigation and treatment has been used since 1987. An important feature of the programme is a register containing information on all cases of prostate cancer in the region, including the patient's national registration number, date of diagnosis, basis of diagnosis (cytology, pathology), tumour stage, histological grade, first line treatment, and date and cause of death. Secondary treatment has also been recorded since 1990, and treatment with prostate specific antigen since 1992. From 1987 to 1995, a total of 5,939 cases of prostate cancer were registered, the annual total increasing from 531 to 779 in 1993, after which there was a slight overall decrease but a small increase in the proportion of local tumours. The proportion of incidental tumours followed the same pattern as the transurethral prostatectomy rate in the region. M- and N-categorisation were done to a greater extent in the under-70 than in the over-70 age group. Orchidectomy is rapidly being replaced by treatment with GnRH (gonadotrophin-releasing hormone) analogues. Over the 9-year period, the total prostatectomy rate decreased from 12.5 to 4.6 per cent. All units responsible for prostate cancer care in the south-east region regularly receive processed updates from the register providing information on diagnostic and therapeutic methods used and their effect on mortality, thus providing a basis for improving the quality of prostate cancer care. Starting in 1997, a similar registration system is to be extended to cover the entire country.

Humans

Morbidity of ultrasound-guided transrectal core biopsy of the prostate without prophylactic antibiotic therapy. A prospective study in 415 cases.

OBJECTIVE: To evaluate prospectively the incidence of complications following transrectal core biopsy of the prostate without prophylactic antibiotic therapy. PATIENTS AND METHODS: The study comprised 426 consecutive patients who underwent transrectal core biopsies of the prostate guided by transrectal ultrasonography (TRUS). The patients were requested to return a completed questionnaire 2 weeks after the examination; 415 patients (97.4%) did so. RESULTS: The predominant complications were haematuria (49.6%) and rectal bleeding (21.7%), which did not require treatment. Twelve patients (2.9%) developed fever and 11 of these were treated successfully with antibiotics. One recovered without treatment. One patient had urinary retention. CONCLUSION: In this study, most complications following TRUS-guided biopsies were minor and required no treatment. Automated needle biopsy is an acceptable option for biopsy of the prostate and does not provoke the need for prophylactic antibiotic therapy. However, it is mandatory to counsel patients before biopsy and to monitor the infection rate. The ultimate need for antibiotic prophylaxis remains to be determined.

Adult

Age-specific reference values for serum prostate-specific antigen in a community-based population of healthy Swedish men.

To establish normal reference values for prostate-specific antigen (PSA) in a Swedish population we investigated 878 healthy men, 56-75 years of age. They were randomly selected from a population of 9171 males in this group. Cancer of the prostate was excluded by digital rectal examination. When digital rectal examination was suspicious for carcinoma of the prostate and/or serum PSA > 4 micrograms l-1, fine-needle aspiration biopsy was performed. Central values, values of variance and reference limits were defined by a non-parametric method in four age groups. A strong positive correlation between PSA values and age was found and the variance increased with age. The relationship between PSA value and age was non-linear. For the age group 56-60 the upper reference limit (95th percentile) was 4.6 micrograms l-1 (confidence interval, CI: 3.9-5.5). For the age groups 61-65, 66-70 and 71-75 the corresponding values were 4.4 (3.8-5.2), 7.6 (6.5-8.9) and 8.4 micrograms l-1 (7.2-9.8) respectively. For the age groups studied the increment over time of the PSA value was 2-8% per year depending on age, with an average increment per year over 15 years of 4.3%. Overall, 11% of our reference sample had a serum PSA level > 4 micrograms l-1. We consider our study population to be representative for a normal Swedish male population in these age groups.

Aged

Randomised study of Casodex 50 MG monotherapy vs orchidectomy in the treatment of metastatic prostate cancer. The Scandinavian Casodex Cooperative Group.

The effect of Casodex (ICI 176,334), a new, once-daily, selective antiandrogen, given as 50 mg monotherapy, was compared with orchidectomy in a randomised, multicentre, open study in 376 patients with metastatic prostate cancer. At 3 months, PSA was reduced by 86% in the Casodex group and by 96% in the orchidectomy group. Treatment failed in 51 patients in the orchidectomy group and 66 showed a subjective response. Treatment failed in 86 patients treated with Casodex and 40 patients showed a subjective response. Patients treated with Casodex maintained their sexual interest better than those in the orchidectomy group. Median survival was significantly longer in the orchidectomy group. Casodex was well-tolerated. The most likely reason for the differences between the groups regarding time to treatment failure and survival is that the dose of Casodex was too small. Further studies with higher doses of Casodex are in progress.

Aged

Prevalence and duration of hot flushes after surgical or medical castration in men with prostatic carcinoma.

A total of 77 men with prostatic carcinoma treated with orchiectomy or a gonadotropin releasing hormone analogue before September 1987 underwent evaluation by a questionnaire regarding vasomotor symptoms. Answers were received from 84% of the patients. Of 63 patients 43 (68%) reported hot flushes during treatment, while 30 (48%) still had flushes 5 years after treatment. Of the latter 30 patients 28 (median 7.6 years after treatment) had vasomotor symptoms at the time of the study. Only 13 of 43 men with vasomotor symptoms after the start of treatment had relief 5 years later. At the time of the study 13 of 30 patients (more than 40%) still had flushes 8 years after castration. Most men reported that the flushes presently had the same frequency and duration as when they started therapy. Contrary to the general belief that the symptoms disappear with time, our study highlighted a long persistence of hot flushes after castration.

Aged

Clinical and economic considerations in the treatment of prostate cancer.

Prostate cancer is a growing health problem with considerable economic consequences. Despite progress in the management of this disease, few areas in medicine generate greater disagreement. The larger part of healthcare resources are allocated to 'halfway technologies' aimed at palliative intervention to prolong life, while a relatively small part goes to measures aimed at preventing or curing the disease. The aetiology of this cancer is multifactorial and no practical measures for primary prevention are known. The number of patients diagnosed with prostate cancer is increasing steadily. The age-adjusted mortality, however, has increased only slightly. In its early stages, prostate cancer is often asymptomatic and is usually not diagnosed until it has advanced. Programmes for the early detection of prostate cancer (screening) claimed to reduce morbidity and mortality are a matter of controversy. Furthermore, there has been much debate regarding optimal treatment in the early stages of the disease. Economic considerations have not as yet been integrated into studies concerning localised prostate cancer. The routine first-line treatment of advanced prostate cancer usually involves some type of endocrine treatment. The most straightforward technique is surgical castration. Oral estrogens are as effective as castration, but have significant cardiovascular adverse effects. These may possibly be prevented if estrogens are given parenterally. A third principal endocrine treatment is the administration of antiandrogens. Medical castration can be attained by the administration of recently developed synthetic peptides, gonadotrophin-releasing hormone {luteinising hormone-releasing hormone (LHRH)} (GnRH) analogue agonists which are given parenterally. The advantage of this type of medical castration is that the trauma of surgical castration and the adverse effects of oral estrogens are avoided. In an attempt to improve the results obtained with endocrine treatment, the concept of combining surgical or medical castration with antiandrogens was introduced. This combination could offer improved response rates and survival in a significant number of patients. However, this advantage must be weighed against the tolerability profiles and the high costs of antiandrogens and GnRH analogues. When using expensive drugs, the duration of treatment is a crucial factor in the total cost. As the length of treatment varies greatly between patients it is difficult to decide the most cost-effective alternative for a single individual. The patient's preference is an important factor when selecting treatment. When there is little or no difference in the effect of different regimens the total lifetime cost is important.(ABSTRACT TRUNCATED AT 400 WORDS)

Androgen Antagonists