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Novel palliative strategies for patients with androgen-independent prostate cancer (AIPC) include targeting the epidermal growth factor receptor (EGFR) family. The aim of the present study was to investigate intrapatient changes of EGFRs during the development of AIPC. In total, 106 symptomatic AIPC patients were identified in whom prostatic biopsies (adenocarcinoma) were available both before the start of androgen deprivation (PRTR biopsy) and after the development of AIPC (AIPC biopsy). All four known subgroups of the EGFR family were determined by immunohistochemistry (IHC): c-erbB-1 (EGFR), c-erbB-2 (HER2/neu), c-erbB-3 (HER3) and c-erbB-4 (HER4). Moderate to strong membrane-specific staining was recorded semiquantitatively (<10% vs >/=10%=IHC stained tumour cells: 'negative' vs 'positive' staining). The medical records were reviewed for clinical variables. During the development of AIPC, intrapatient changes occurred in two opposite directions for each of the four EGFRs: negativity changed to positivity, and vice versa, statistically significant only for the increase of c-erbB-1 expression (P=0.001). The c-erbB-2 expression in the AIPC biopsy was associated with a significantly shorter survival from the time of the AIPC biopsy (P=0.029). Our results support ongoing therapeutic attempts of EGFR inhibition in subgroups of patients with prostate cancer. Further research is needed to understand the function of EGFRs in this malignancy.

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The determination of serum prostate specific antigen (PSA) has made the diagnosis of prostate cancer easier. PSA is also used extensively in the follow-up of patients, both treated and untreated. On the basis of material from 308 patients who were mainly managed conservatively, we discuss the usefulness of this practice. It is important to monitor PSA after radical treatment because an increase may indicate local recurrence. In some patients this may lead to further treatment with cure as the aim. For patients under observation only, or those being treated by endocrine intervention, the value of regular PSA measurements is less certain. Where such patients were followed up for at least three years, we found considerable overlaping of PSA values among patients with different outlooks. Within the present therapeutic possibilities it may be better to base their management on clinical signs rather than on PSA. Regular measurements of PSA lead to focusing on this variable, causing unnecessary distress to patients months, or even years, before clinical progression of the disease.

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PURPOSE: Instability of prostate specific antigen (PSA) in serum might complicate the interpretation of the free-to-total PSA ratio. We studied the in vitro stability of free PSA and total PSA in serum of patients with prostate cancer or benign prostate hyperplasia (BPH), and of elderly men without known prostate disease. Furthermore, we investigated conditions to stabilize the in vitro values in serum. MATERIALS AND METHODS: The effects of storage at 4C on free and total PSA were investigated in serum of 32 men with prostate cancer, 25 with BPH and 29 older than 70 years. All had total PSA less than 25 microg./l. The influence of total PSA levels on in vitro changes in free-to-total PSA was studied in serum of 39 other prostate cancer patients (total PSA 1.7 to 298 microg./l.). Stabilization studies were performed in yet another series of samples from 54 prostate cancer patients (total PSA 1.3 to 238 microg./l.) by adjustment of serum pH to 5.5 before storage. Free and total PSA was measured by a commercial immunofluorometric assay, as well as by in-house immunofluorometric assays. Statistical analyses of the results were performed by analysis of variance with repeated measures. RESULTS: We found no difference between the results obtained by the 2 assay systems. After 7 days at 4C there was a slight decrease in total PSA in sera of prostate cancer patients, BPH patients and men older than 70 years. A decrease in mean free PSA values occurred in all groups (21.3, 15.7 and 14.6%, respectively). The decrease of free PSA with time was significant (p <0.0001) in all groups but there was no significant difference among the groups (p=0.16). The concomitant decrease in free-to-total PSA ratio was significant in all groups (p <0.0001). This change was group dependent (p=0.003), with the largest decrease in the prostate cancer group. Large interindividual differences were observed. Storage at 4C for 7 days of sera of 39 patients with localized and disseminated prostate cancer (total PSA 1.7 to 298 microg./l.) gave a more pronounced decrease in free PSA than in total PSA. Adjustment of serum pH to 5.5 had a stabilizing effect on free PSA and on the free-to-total PSA ratio, giving a significantly smaller change in both values (p <0.0001). CONCLUSIONS: In vitro instability of free PSA in serum and large interindividual differences should be considered when using the ratio of free-to-total PSA in evaluation of patients with suspected prostate cancer. Serum samples should be stored frozen if not analyzed immediately or acidified to pH 5.5. Interpretation of data from determination of free-to-total PSA ratio should be done with caution if the sampling and storage conditions are not known.

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Patients with newly diagnosed prostate cancer who were registered in one hospital during two recent one-year periods were studied with regard to causes and consequences of the diagnosis. 65 new cases were registered in 1991 and 102 in 1994. These constitute about 90% of all new cases in the area served by the hospital, and are representative of the population to this extent. In only one of the 16 patients treated with curative intent was the diagnosis made as a consequence of routine determination of prostate specific antigen (PSA) when he was asymptomatic. On the other hand, PSA-assay in asymptomatic men led to an increasing number of patients being made aware of a disease for which no treatment was recommended. This was partly because most of the patients diagnosed in this manner were elderly (mean age 72). A plea is made to restrict this practice to younger men.

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OBJECTIVE: To quantify the need for treatment and care in patients with conservatively treated prostate cancer. PATIENTS AND METHODS: All men who had been diagnosed with prostate cancer in a defined geographical area and who died within the period 1987-91 were identified. Patients treated with curative intent were excluded. Medical records from hospitals, nursing homes and community nurses for the period from diagnosis until death were scrutinized for the remaining 174 patients. RESULTS: Of the 174 patients, 95% were symptomatic at diagnosis and 62% died from prostate cancer. All but two patients were hospitalized for prostate cancer, for a mean of 1 month. Thirty-six per cent needed regular nursing in nursing homes or by community nurses at home. Complications requiring hospitalization or long-term catheterization occurred in 49%. Prostatic surgery was performed in 66% and androgen ablation in 76% of the patients; palliative irradiation was given to 16% and 50% received analgesics regularly, including opiates or equivalents in 37%. Prednisone was given to 29%, after the failure of androgen ablation. CONCLUSION: Our findings demonstrate the considerable burden imposed both on patients and health-care resources by symptomatic prostate cancer, conservatively treated. There are few data available for comparison.

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Prostatic carcinoma, if detected early, may be cured by radical surgery or radiotherapy. In Norway, only a minority of patients (about 5%) received this treatment in 1988. However, diagnosis of possibly localised cancer was made in 31% of patients, most of whom were probably only observed and not treated unless progression occurred. This conservative attitude is representative of European practice but conflicts with the current approach in the United States. In view of the possible complications of such treatment there is no material to prove that radical treatment would benefit the populations as a whole. Nor has this been disproved. Such treatment should only be considered on the basis of strict criteria and for strongly motivated patients, who should be fully informed of the possibilities of complications and of being cured, and also about alternative treatment, including watchful waiting.

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Early diagnosis is a prerequisite for permanent cure of prostatic carcinoma, and screening of asymptomatic men has been suggested. This proposal is discussed in relation to criteria for meaningful screening, and we conclude that most of these criteria are not fulfilled. While prostatic carcinoma is a major health problem, it has not been proved that early diagnosis and treatment, although undoubtedly useful for some, is profitable for the population as a whole. Many cases of early disease represent latent or slowly growing disease, for whom radical surgery or irradiation, with possible complications, would mean overtreatment. At present, screening cannot be advised for the general population, but should be considered for men at risk because of a history of prostatic cancer among close relatives.

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Prostate-specific antigen has replaced acid phosphatase as a more sensitive marker of prostatic cancer. It is organ-specific but not cancer-specific. However, high serum level is more often indicative of cancer than of benign hyperplasia. The authors discuss the value of prostate-specific antigen in diagnosis and prognosis, and the indications for its use. This test should be included in the examination of men with prostatic symptoms and in men below age 70-75 with a suspicious finding in the prostate on digital rectal examination. At present, we do not recommend it for screening purposes, except in men with a family history of cancer of the prostate gland.

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In 1842, F. C. Faye obtained the degree of doctor of medicine. He was the fourth person to do so in Norway. His dissertation was on the seminal vesicles. These were the focus of much attention at that time, when so-called seminal flux was considered both a serious symptom and the cause of many ills, both mental and physical. The treatise, which was in Latin, and the academic proceedings involved serve to illustrate the medical world of his time. They also provide a background for a brief review of today's conception of the seminal vesicles, which is still incomplete and not entirely satisfactory. Newer methods of imaging, such as transrectal ultrasonography, may shed new light on the pathology of these organs.

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Total cystectomy with or without preoperative radiotherapy was performed in 122 patients with T2/T3 bladder carcinoma (group 1:42 patients, 23 X 2 Gy; group 2:34 patients, 5 X 4 Gy; group 3:46 patients, 0 Gy). Crude and disease-free survival was 40 and 54%, respectively, in this retrospective study. No survival difference was observed between the different groups. 'Stage reduction' in the cystectomy specimen (P less than T) was the only significant prognostic parameter and was seen in 24, 15 and 18 patients from groups 1, 2 and 3, respectively. Distant metastases were found in 47 patients during follow-up, equally distributed between the 3 groups, but significantly less often in patients with 'stage reduction'. In patients with T2/T3 bladder cancer, the role of precystectomy radiotherapy remains undefined, though there might be a nonidentifiable subgroup of patients (about 20%) who probably benefit from preoperative irradiation. Preferably short-term radiotherapy should be applied. As distant metastases represent the most common reason for treatment failure after total cystectomy, the role of adjuvant systemic chemotherapy has to be explored in further clinical studies.

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During a 5 year period, 500 stones from the upper urinary tract and 100 from the urinary bladder of as many unselected and consecutive patients were obtained in one hospital and analysed crystallographically. 90.4% of the upper urinary tract stones and 65% of the bladder stones belonged to the groups of calcium stones, while 6.6% and 24%, respectively, were triple phosphate stones. The contribution of calcium stones to this material is higher and that of triple phosphate stones lower than in comparable materials. Frequency variations between materials also exist within the groups of calcium stones, and for uric acid, urate and cystine stones. On the basis of published material, it is not possible to say if these differences are renal or reflect variations in the selection of stones and the methods of analysis. Reports on stone materials should include information on these aspects in order to allow meaningful comparison. Distinction between stones from the upper urinary tract and from the bladder is mandatory. The composition pattern reported here is believed to be as representative as is possible to obtain. A major part of stones from the upper urinary tract is, however, lost for analysis following spontaneous passage. Such stones are more often pure calcium oxalate and less often triple phosphate stones than those which are obtained by surgical methods, and the extent to which they are obtained will influence the findings in stone materials.

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On the basis of routine clinical and laboratory investigations, one or more probable or possible causes of stone formation were established in 27% of upper urinary tract and 98% of bladder stone patients. In the upper urinary tract, causes were usually found for triple phosphate and pure calcium phosphate stones and rarely for pure calcium oxalate stones. Except for cystine stones and largely for triple phosphate stones there was no definite correlation between the composition of stone and causes. Uric acid and urate stones were often not associated with obvious causes, but their demonstration should lead to further investigations. In a small group of recurrent calcium stone formers examined for hypercalciuria, hyperoxaluria, hyperuricosuria, and renal tubular acidosis, positive findings were noted for 65%, but there was no consistent correlation between these findings and the types of stone. Stone analysis is most useful in so far as it identifies or excludes triple phosphate, cystine, and uric acid/urate stones. This may be done by simple chemical analysis. Certain rare components may, however, be overlooked, as will details of stone structure, unless crystallographic methods are employed.

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175 stones from 70 recurrent stone formers with each at least two stones available for analysis were studied crystallographically. The chance that a subsequent stone belonged to the same of five major stone groups was 65% but rose to 91% if three of these groups were considered as one (calcium stones). Other findings, however, indicate that distinction between the three groups of calcium stones is of interest. Thus, pure calcium oxalate stones (Ox) did not occur in the same patients as pure calcium phosphate stones (P). In comparable stones containing both the above types of components (OxP), the calcium phosphate content was significantly lower (average apatite content per stone 9%) in stones from patients who also had Ox stones than (37%) in those who had associated P stones. Also, the stone nucleus was frequently Ox in the OxP stones from the former and usually P in the OxP stones of the latter patients. Brushite occurred in 10% of the stones, which is more frequent than in unselected stone materials and largely due to a tendency for it to recur in a few patients. Patients who provide more than one stone for analysis appear to differ considerably in stone composition from stone patients in general, and inclusion of several stones from some patients will lead to bias in materials purporting to reflect stone composition in a population. When available, several stones from each patient should preferably be analysed. Exceptions may be made for cystine and, possibly, pure uric acid stone patients.

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Quantitative analytical findings on upper urinary tract stones from 500 patients are reported and compared to data in the literature. Methods of presentation of quantitative data are discussed. A wide range of findings between recurrent stones in the same patient and between stones from patients with the same cause of stone formation was found. No immediate clinical value of quantitation can be seen, but larger materials and correlation with metabolic investigations in stone formers may reveal correlations of clinical interest. Quantitative observations may identify groups of patients and types of stones not recognised on the basis of qualitative analysis. Examples of this are given for calcium oxalate-calcium phosphate stones and for stones containing brushite. The organic matrix which usually contributes 2-3% of stone mass was not considered, but distinctly visible and separate organic material in 7 stones was quantitated by visual estimate. 32 stones were incomplete, and their quantitation may not be wholly representative. Their exclusion, however, would have led to major bias because most were large and nearly half were triple phosphate stones, both properties being relatively rare. In cases of multiple stones, usually only one was quantitated. Seventy patients provided more than one stone for analysis (Otnes, 1983b), but except when specifically stated only the first stone is considered.

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The weight of 500 upper urinary tract stones is correlated here with qualitative and quantitative stone analysis findings. The average weight was 725 mg, but 65% of the stones weighed less than 200 mg. With increasing weight, a shift in dominance from calcium oxalate to triple phosphate occurs. Stone materials differ in weight distribution, and reports of composition in different weight ranges may facilitate comparison and compensate for bias in selection of stones for analysis. Quantitative observations on stones consisting of calcium oxalate mono- and dihydrate with apatite show that the proportions of these components are much the same in all weight ranges, but vary with the composition of the nucleus. This is taken to support the significance of apatite in such stones and to indicate that stones with different nuclei should be considered separately. Similar observations on pure calcium oxalate stones may support a primary role of calcium oxalate monohydrate in the deposition of many such stones. Weight data for bladder stones are presented briefly and show a wide range of weights for all types of composition.

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