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BACKGROUND: Following radical nephro-ureterectomy for urothelial carcinoma of the upper urinary tract (UUT), the reported bladder recurrence rate of urothelial carcinoma is 22-47%. A single intravesical instillation of chemotherapy within 10 days following nephro-ureterectomy has the potential to decrease the risk of a bladder recurrence significantly. Despite recommendation by the European Association of Urology guideline to administer a single instillation postoperatively, the compliance rate is low because the risk of extravasation of chemotherapy. AIM: To reduce the risk of bladder cancer recurrence by a single intravesical instillation of Mitomycin immediately (within 3 h) before radical nephro-ureterectomy or partial ureterectomy. METHODS: Adult patients (age ≥ 18 years) with a (suspicion of a) urothelial carcinoma of the UUT undergoing radical nephro-ureterectomy or partial ureterectomy will be eligible and will receive a single intravesical instillation of Mitomycin within 3 h before surgery. In total, 170 patients will be included in this prospective, observational study. Follow-up will be according to current guidelines. RESULTS: The primary endpoint is the bladder cancer recurrence rate up to two years after surgery. Secondary endpoints are: a) the compliance rate; b) oncological outcome; c) possible side-effects; d) the quality of life; e) the calculation of costs of a single neoadjuvant instillation with Mitomycin and f) molecular characterization of UUT tumors and intravesical recurrences. CONCLUSIONS: A single intravesical instillation of Mitomycin before radical nephro-ureterectomy or partial ureterectomy may reduce the risk of a bladder recurrence in patients treated for UUT urothelial carcinoma and will circumvent the disadvantages of current therapy.

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OBJECTIVE: To evaluate the need for a bone scan as a routine staging procedure in patients with newly diagnosed prostate cancer in relation to serum prostate-specific antigen (PSA) and alkaline phosphatase (ALP) levels, and thus determine whether a reduction of the use of this staging method is possible in patients with a low probability of osseous metastasis. PATIENTS AND METHODS: The results of bone scans were related retrospectively to levels of serum PSA and ALP in 363 patients with prostate cancer newly diagnosed between 1989 and 1997. RESULTS: Of 363 consecutive patients, 111 had a positive bone scan. In 19 of 144 (13%, "missed diagnosis") patients with a PSA level of < 20 ng/mL the bone scan was positive. In 125 patients (49%, "false-positives") with a PSA level of > 20 ng/mL the bone scan was negative. A threshold level of 100 U/L for ALP gave a better balance for the number of "false-positives" and "missed diagnosis". ALP values correlated better with an abnormal bone scan than did PSA levels; ALP levels of > 90 U/L indicated a 60% chance for the presence of bone metastases. CONCLUSION: Patients with newly diagnosed and untreated prostate cancer should undergo bone scintigraphy if there is bone pain or if ALP levels are > 90 U/L. Recent reports discourage the routine use of a bone scan when the serum PSA level is <20 ng/mL. However, the present series suggests there is a greater chance of a positive bone scan in patients with low PSA levels; these findings need further confirmation.

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OBJECTIVE: To assess the predictive role of the bone markers alkaline phosphatase (ALP) and urinary deoxypyridinoline (DPD), as indicators of bone turnover, at baseline in patients with prostate cancer. PATIENTS, SUBJECTS AND METHODS: Urinary DPD, serum ALP and prostate-specific antigen (PSA) were evaluated in 23 patients with benign prostatic hyperplasia (BPH), 115 with prostatic carcinoma, of whom 21 had bone metastasis, and in 16 age-matched control subjects. RESULTS: Patients with newly diagnosed prostate cancer and bone metastasis had a higher urinary excretion of DPD, and a higher serum PSA and ALP than had patients with BPH and those with prostate cancer but no metastasis. Receiver operating curve analysis for PSA, ALP and DPD showed a significant discriminating ability for positive and negative bone scans (P = 0.0684). However, from logistic regression of the combinations, only serum ALP was a significant independent predictor of bone metastasis in patients with prostate cancer. CONCLUSION: Serum ALP or urinary DPD are the best predictors of bone metastasis in patients with prostate cancer; further studies with more patients are required.

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In three men, aged 44, 47, and 48 years, prostatic carcinoma was diagnosed after a long delay, more than eight months after the onset of symptoms (obstructive and irritative micturition problems, erectile dysfunction, and haemospermia). The cancer was suspected on eventually performed rectal palpation and confirmed in biopsies. The serum prostate-specific antigen (PSA) levels were moderately increased. All were treated with goserelin and flutamide and radiotherapy on the emerging metastases (two patients). Two patients died, the third one, who had received antibiotic treatment for three months because at first prostatitis was suspected, was still in remission at the last follow up. Prostate cancer in young men is rare and may demonstrate aggressive biological behaviour. The age group less than 50 years of age accounts for 0.8% to 1.1% of all patients with prostate cancer. This form of the disease responds poorly to radiation or hormonal therapy and is often already too advanced for surgery. The symptoms at presentation of prostate cancer in young men are quite similar to those in prostate cancer patients beyond the fifth decade. When carcinoma grows beyond the margins of the prostate the prognosis is poor. In all men with micturition problems, rectal palpation of the prostate should be carried out as a routine.

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PURPOSE: To assess the reliability of first and second generation PSA assays. MATERIALS AND METHODS: In the present investigation we sought to compare pretreatment serum PSA levels determined by a first (IMx) and a second (IMMULITE) generation PSA assays to determine whether there were differences. Sera from 545 men were investigated in the range > 0 - 5330 microg/L, and prostatic histology was known, based on either transrectal ultrasound (TRUS), guided systematic needle biopsies, or transurethral resection or prostatectomy. RESULTS: Over the entire range there was an excellent correlation (r > 0.97) between the IMx and the IMMULITE PSA assays. When analyzed according to histology, there was an equivalent slope in the PSA ranges for patients with benign prostatic hyperplasia compared with prostate cancer patients. The area under the ROC curve for the IMx for the total PSA range was 0.7860, and for the IMMULITE assay the area under the ROC curve was 0.7810, a striking resemblance and not different significantly (p=0.87). CONCLUSION: For the majority of men, the first (IMx) and second (IMMULITE) generation PSA assays are equivalent. Small differences between both assays will not be of clinical significance for most men, but should be considered when comparing results of different assays in sequential determinations for a specific man.

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OBJECTIVE: A study was performed to evaluate the free-to-total prostate-specific antigen (PSA) ratio for discriminating benign prostatic hyperplasia (BPH) or prostate cancer in the intermediate PSA range (2.0-10.0 microg/l) in patients referred for prostate evaluation. In addition, the relationship of free-to-total PSA ratio and tumor grade in prostatic cancer cases, implying a higher concentration of complex PSA in poorly differentiated cancer, was assessed for its predictive value of tumor aggressiveness at the time of diagnosis. PATIENTS AND METHODS: Seven hundred and sixteen patients referred to the out-patient clinics of two urological departments were included in this prospective study. Blood samples were taken for total immunoreactive and free PSA (IMMULITE) determinations prior to any manipulation. The patients were grouped according to their PSA levels: 2.0-4.0 microg/l, 4.0-10.0 microg/l, 10.0-20.0 microg/l and > or = 20.0 microg/l. All patients were categorized, after histological confirmation, as having BPH (n = 423) or prostate cancer (n = 293). In patients with cancer the tumor grade was also assessed. RESULTS: In patients with serum immunoreactive PSA levels in the 2.0-4.0 microg/l range, a free-to-total PSA ratio lower than 22% predicted the presence of prostate cancer with a sensitivity of 67% and a specificity of 63%. The positive- and negative-predictive values were 29% and 90% respectively. Receiver-operating characteristic curve analysis indicated a free-to-total PSA ratio of 22% to be the optimum discriminatory level in this low PSA range. For patients with a serum PSA level between 4.0 and 10.0 microg/l, the threshold ratio of 18% gave a sensitivity of 70%, a specificity of 70%, a positive-predictive value of 46% and a negative-predictive value of 87%. Men with a well differentiated grade of prostate cancer had higher free-to-total PSA ratios than those with less differentiated tumors (p = 0.01). CONCLUSIONS: Our data indicate that the free-to-total PSA ratio, in patients with prostatic disease and with PSA levels in the 2.0-10.0 microg/l range, gives a significant improvement in prediction of cancer over the total immunoreactive PSA value alone. Because of the correlation between a higher tumor grade and a lower free-to-total PSA ratio, this ratio may be helpful in assessing the risk of a poorly differentiated cancer.

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BACKGROUND: Telomerase activation is thought to be essential for the immortality of cancer cells. It may be a prognostic factor in small volume well differentiated prostate cancers and hence a guide for the aggressiveness of the approach. The length of the chromosome tips (telomeres) are maintained by a specific enzyme (telomerase) independently of the normal cell division cycle. Although telomerase is not expressed in most normal human tissues, it is expressed in most human tumours. For the detection of telomerase in small prostate needle biopsy samples a recently developed telomeric repeat amplification protocol (TRAP) assay was used. The aim of the present study was: to measure telomerase activity in human prostate samples, and to evaluate the applicability of this assay on specimens from a prostate biopsy. MATERIALS AND METHODS: From 36 patients referred for lower urinary tract symptoms (LUTS) or suspicion of having prostate cancer a total of 288 prostate biopsy samples were obtained (8 in each patient). When the digital rectal examination was abnormal and/or when the PSA level was elevated in L.U.T.S., or asymptomatic patients' tissue samples were obtained by transrectal ultrasound (TRUS) guided biopsies. Samples were tested for telomerase activity by a modified TRAP and forwarded for histology. RESULTS: In 19 out of 36 patients prostate cancer was diagnosed on histology. In 11 of these 19 tumours substantial telomerase activity was detected, whereas only very low telomerase activity existed in 2 of 17 samples from benign prostatic hypertrophy (BPH) patients. In this small series the relative telomerase activity in prostate cancer correlated with histopathological grade. CONCLUSIONS: Our results show the applicability of a TRAP assay to measure telomerase activity in small needle biopsied prostate samples. In poorly differentiated and metastatic cancer we observed that levels of telomerase activity were high. To establish accuracy and to distinguish the 'relative good from the ugly' further study is needed.

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Invasion of prostatic adenocarcinoma into the seminal vesicles (SV) is generally accepted as an index of poor prognosis. The pre-operative identification of SV invasion is an important element in staging since it may alter subsequent treatment decisions. We studied the possibility of diagnosing SV invasion with two biopsies from the junction between the prostate and seminal vesicles. Also we studied the correlation of several prognostic factors with the risk of clinical stage T(1,2,3) prostate cancer patients of having cancer growth into the seminal vesicles. Consecutive patients referred for transrectal ultrasound (TRUS) and biopsy because of clinical suspicion of prostate cancer were examined. This staging procedure was evaluated in patients who underwent a pelvic lymphadenectomy and radical retropubic prostatectomy (RRP). In 83 out of 138 patients prostate cancer was detected whereas 55 patients had benign disease. In 44% of prostate cancer patients a positive SV biopsy was found. The accuracy of the biopsies adjacent to the junction of the SV and the prostate was 91%. The best predictors for SV invasion were tumor grade of the biopsy sample (P<0.001), serum prostate-specific antigen (PSA) (P<0.0005), PSA density (P<0.0005) and clinical stage (P<0.0005). No significance was found in the relation to seminal vesicle involvement with free/total (f/t) PSA ratio (P=0.588) for the prostate cancer group (SV+ and SV-). In a receiver operating characteristic curves analysis, PSA density was significantly more accurate for prediction of SV invasion than PSA or f/t PSA ratio. In five prostatectomized patients (and negative SV biopsy) no SV invasion was found in the final pathologic examination either. SV biopsy at the junction of the SV and prostate is accurate for staging with high efficacy and low morbidity. To predict SV invasion in prostate cancer patients, PSA density was more accurate than PSA or f/t PSA ratio. The determination of the f/t PSA ratio in patients with low and intermediate PSA levels (eg <15 &mgr;g/L) is not useful to estimation of the risk of seminal vesicle involvement. The combination of serum PSA concentration, PSA density, tumor grade from the biopsy specimens ad clinical stage provides the best prediction of SV invasion. These parameters are identical to the conventional predictors of pathology after RRP. SV biopsies may provide additional information; if one or both basal biopsies are positive, a clinical T(1,2) disease is altered to T(3). Hence SV biopsy is useful for selection of patients who might obtain good results from RRP for prostate cancer. Prostate Cancer and Prostatic Diseases (2000) 3, 100-106

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Four patients, men aged 81, 65, 69 and 52 years, presented with painless lymphomas, pain in the lower back and legs, venous thrombosis in an arm, and headache, vomiting and other neurological complaints, respectively. They were found to have carcinoma of the prostate with metastases. After antiandrogen therapy the symptoms resolved; 2 men died after 2 years and 2 are still alive, 2 and 5 years later. In men with unexplained complaints, it is advisable to perform a thorough physical examination, including digital rectal examination and a prostate specific antigen determination.

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Prostate specific antigen (PSA) is currently the tumour marker of choice for prostatic carcinoma. Various indices of PSA have been developed in an attempt to refine its sensitivity and improve its clinical value. These include the ratio of serum PSA level and prostate volume, the rate of change of the PSA level with time, age-referenced PSA, and the proportion of free PSA in serum relative to total PSA (free to total PSA ratio). The free to total PSA ratio is lower in patients with prostate cancer than in those with elevated PSA levels due to benign prostatic hyperplasia.

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PURPOSE: We demonstrate the effectiveness of intraureteral streptokinase instillations for the resolution of an insoluble blood clot in the renal pelvis. MATERIALS AND METHODS: A patient with renal adenocarcinoma had prolonged hematuria related to involvement of the "pyelum" by the tumor. An insoluble blood clot obstruction of the left renal collecting system developed as a consequence of epsilon aminocaproic acid therapy, which was treated with low dose streptokinase through a ureteral catheter. RESULTS: Complete resolution of the clot and obstruction occurred within 3 days of therapy. CONCLUSIONS: This relatively simple approach should be used for the treatment of obstruction before radical surgery is performed.

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A case of a 50-year-old woman with aortoiliac arteriosclerosis and an associated horseshoe kidney is presented. The diagnosis of this unusual combination was made prior to surgery; reconstruction was done by a Dacron bifurcation prosthesis. Ultrasonography, intravenous pyelography and aortography is important for "surgical planning".

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