False-positive screening results in the Finnish prostate cancer screening trial.

BACKGROUND: There is evidence that prostate cancer (PC) screening with prostate-specific antigen (PSA) serum test decreases PC mortality, but screening has adverse effects, such as a high false-positive (FP) rate. We investigated the proportion of FPs in a population-based randomised screening trial in Finland. METHODS: Finland is the largest centre in the European Randomized Study of Screening for Prostate Cancer. We have completed three screening rounds with a 4-year screening interval (mean follow-up time 9.2 years) using a PSA cutoff level of 4.0 ng ml(-1); in addition, men with PSA 3.0-3.9 and a positive auxiliary test were referred. An FP result was defined as a positive screening result without cancer in biopsy within 1 year from the screening test. RESULTS: The proportion of FP screening results varied from 3.3 to 12.1% per round. Of the screened men, 12.5% had at least one FP during three rounds. The risk of next-round PC following an FP result was 12.3-19.7 vs 1.4-3.7% following a screen-negative result (depending on the screening round), risk ratio 3.6-9.9. More than half of the men with one FP result had another one at a subsequent screen. Men with an FP result were 1.5 to 2.0 times more likely to not participate in subsequent rounds compared with men with a normal screening result (21.6-29.6 vs 14.0-16.7%). CONCLUSION: An FP result is a common adverse effect of PC screening and affects at least every eighth man screened repeatedly, even when using a relatively high cutoff level. False-positive men constitute a special group that receives unnecessary interventions but may harbour missed cancers. New strategies are needed for risk stratification in PC screening to minimise the proportion of FP men.

Prostate cancer incidence among finasteride and alpha-blocker users in the Finnish Prostate Cancer Screening Trial.

BACKGROUND: The Prostate Cancer Prevention Trial has shown a protective effect of finasteride on prostate cancer in low-risk men. It is uncertain whether similar results can be expected when finasteride is used to treat benign prostatic hyperplasia. METHODS: We performed an observational cohort study within the Finnish Prostate Cancer Screening Trial. Using a comprehensive prescription database on medication reimbursements during 1995-2004 of men using finasteride or alpha-blockers for benign prostatic hyperplasia, we evaluated prostate cancer incidence among 23 320 men screened during 1996-2004. RESULTS: Compared to medication non-users, overall prostate cancer incidence was not significantly affected in finasteride users (hazard ratio 0.87; 95% CI 0.63-1.19). Incidence of Gleason 2-6 tumours, however, was decreased among finasteride users (HR 0.59; 95% CI 0.38-0.91), whereas incidence of Gleason 7-10 tumours was unchanged (HR 1.33; 95% CI 0.77-2.30). The protective effect concerned mainly screen-detected tumours. Overall prostate cancer risk was not significantly reduced among alpha-blocker users relative to non-users, but decreased incidence of high-grade tumours was observed (0.55; 95% CI 0.31-0.96). CONCLUSIONS: The detection of low-grade, early-stage tumours is decreased among men who use finasteride for symptomatic BPH. The protective effect of finasteride can also be expected in men with benign prostatic hyperplasia.

Specificity of serum prostate-specific antigen determination in the Finnish prostate cancer screening trial.

Specificity constitutes a component of validity for a screening test. The number of false-positive (FP) results has been regarded as one of major shortcomings in prostate cancer screening. We estimated the specificity of serum prostate-specific antigen (PSA) determination in prostate cancer screening using data from a randomised, controlled screening trial conducted in Finland with 32 000 men in the screening arm. We calculated the specificity as the proportion of men with negative findings (screen negatives, SN) relative to those with negative and FP results (SN/(SN+FP)). A SN finding was defined as either PSA

Bladder management in persons with spinal cord lesion.

STUDY DESIGN: Cross-sectional clinical descriptive prevalence study. OBJECTIVE: To evaluate the methods of self-reported bladder management, the frequency of urinary tract infection (UTI) and subjective disturbance of bladder problems of all those individuals with traumatic spinal cord lesion (SCL) living in Helsinki area. SETTING: : Helsinki, Finland. METHODS: A total of 152 persons with SCL were found in the Helsinki area (546 000 inhabitants). A structured questionnaire was sent to all subjects and they were invited to a clinical visit. RESULTS: The final study-group consisted of 129 (85%) subjects. They were defined into seven specific subgroups of bladder management: 14 (11%) subjects in the normal voiding group, 15 (12%) in the controlled voiding group, 16 (12%) in the clean intermittent catheterization (CIC) group, 30 (23%) in the mixed group, 31 (24%) in the suprapubic tapping group, 16 (12%) in the compression or straining group and seven (5%) in the catheter or conduit group. The frequency of UTI was highest in the mixed group. The bladder management was a biggest bother to the subjects in the compression or straining group. CONCLUSIONS: This prevalence study assesses the self-reported bladder management methods in all the persons with traumatic SCL in the Helsinki area. The subjects who used CIC and other methods for bladder management had more problems than others. These subjects might manage better by using either CIC or suprapubic tapping as the only method for bladder emptying.

A randomized trial of choice of treatment in prostate cancer: the effect of intervention on the treatment chosen.

OBJECTIVE: To determine whether different approaches in the choice of treatment affect the treatment chosen by the patient for prostate cancer. PATIENTS AND METHODS: We conducted a randomized trial with 210 men who had a histologically confirmed diagnosis of prostate cancer in 1993-94 at four major hospitals in Finland. After obtaining informed consent the men were randomized either to an intervention arm, in which there was greater patient participation in the choice of treatment following a structured procedure, or a control arm in which the standard approach, i.e. a standardized treatment protocol, was used. The main outcome measure of the analysis was the primary treatment chosen for prostate cancer. RESULTS: In the enhanced participation arm patients not eligible for radical prostatectomy chose orchidectomy less frequently and favoured nonsurgical endocrine treatment than in the treatment protocol arm. Radical prostatectomy was the most commonly chosen treatment option in both arms among men with operable cancer. The way treatment options were presented affected the treatment chosen for prostate cancer. CONCLUSION: Patients with prostate cancer are willing and able to take an active role in making decisions. The preferences of patients with prostate cancer in the choice of treatment may differ from the priorities of the physicians.

The effect of photodynamic therapy on rat urinary bladder with orthotopic urothelial carcinoma.

OBJECTIVE: To assess the effect of whole-bladder photodynamic therapy (PDT) on a rat model with orthotopic superficial bladder cancer, as PDT is an alternative intravesical therapy for treating superficial bladder cancer, based on an interaction between a photosensitizer and light energy to induce oxygen radicals that destroy tissue by lipid peroxidation. MATERIALS AND METHODS: In all, 76 female Fischer F344 rats were inoculated intravesically with AY-27 tumour cells. After establishing superficial tumour, 24 rats were treated with PDT using aminolaevulinic acid (ALA)-induced protoporphyrin IX as a photosensitizer, and a continuous-wave argon pumped-dye laser (638 nm). At 4 h after intravenous (300 mg/kg) or intravesical (100 mg/mL) administration of ALA the bladders were intravesically exposed to a 40 J/cm(2) light dose; 12 rats received no ALA but were exposed to the same light dose. Before administering ALA, urine cytology samples were taken for analysis. At 3 or 21 days the treated rats were killed and morphological changes in the bladder walls analysed by light microscopy. Forty rats served as controls to examine the presence of tumour. RESULTS: The tumour established in 33 of 40 rats (83%) in the controls, but after PDT with intravesical ALA there was carcinoma in only in one of 12 (P < 0.001, Pearson's chi(2) test). After PDT with intravenous ALA there was carcinoma in five of 11 rats (P = 0.063, Pearson's chi2 test). In the control group of 12 rats receiving only light energy there was carcinoma in three (P = 0.001, Pearson's chi(2) test). Histologically, at 3 days after PDT there was only mild superficial damage in all six rats treated intravesically. Bladder wall destruction reached the muscular layer, with an abscess in one of six rats treated intravenously. After 3 weeks of PDT there was muscular necrosis with perforation and abscess from catheterization two of six rats treated intravesically and in three the bladder wall totally recovered. In the intravenous group the bladder walls were normal or had only mild superficial damage. Cytology of the urine sediment failed to detect half the tumours in the treatment groups. CONCLUSION: These results support the use of PDT with intravesical ALA-induced protoporphyrin X for treating superficial bladder carcinoma. Intravesical was better than intravenous ALA in eradicating bladder carcinoma with PDT.

HSV-tk gene therapy for human renal cell carcinoma in nude mice.

We have treated Caki-2 human renal cell carcinoma in vivo using herpes simplex virus thymidine kinase (HSV-tk) gene therapy. Both stably transduced Caki-2 tumors, generated using retrovirus-mediated ex vivo HSV-tk gene transfer and direct intratumoral adenovirus-mediated HSV-tk gene transfer of wild type tumors, were tested. Similar treatments with LacZ containing retro- and adenoviruses were used as controls. The outcome was evaluated by imaging the tumors before and after the treatment with magnetic resonance imaging, and using histology, immunocytochemistry, and survival analysis. When implanted orthotopically into nude mouse kidneys, Caki-2 cells formed reproducible cystic papillary kidney carcinomas. In vivo magnetic resonance imaging provided an important tool for the evaluation of tumor growth. Transduction efficiency of wild-type tumors in vivo with adeno-LacZ was 22+/-14%. Significant tumor regression was achieved with direct intratumoral adeno-HSV-tk transduction followed by intraperitoneal ganciclovir (GCV) (P<.001). Also, the treatment of stably transduced Caki-2 tumors with intraperitoneal GCV resulted in a significant treatment response in the HSV-tk group as compared to the LacZ group (P<.009). Increased apoptosis and macrophage infiltrations, reduced proliferation, and degenerative changes were observed in the tumors treated with HSV-tk and GCV. Also, significant prolongation in survival was achieved with adeno-HSV-tk- and GCV-treated mice as compared to the controls. It is concluded that adeno-HSV-tk gene therapy may be useful for the treatment of renal cell carcinoma in vivo.

Effect of photodynamic therapy on urinary bladder function: an experimental study with rats.

Photodynamic therapy (PDT) produces localized necrosis with light after prior administration of a photosensitizing drug. The problems with laser light dosimetry and complications relating to bladder function appear to be important limiting factors of PDT in urology. Photodynamic therapy on urinary bladder with normal epithelium of rats was performed using an argon ion laser as an energy source, with aminolevulinic acid (ALA)-induced protoporphyrin IX (PpIX) photosensitizer. Four hours after ALA intravenous administration, the bladders were intravesically radiated with light doses 20, 40, or 80 J/cm2. Animals in the control group did not receive ALA and were radiated with 20 J/cm2 light dose. Three weeks prior to PDT, the bladder capacity and pressure changes during filling cystometry were assessed. Cystometrics were repeated 1, 3, 7, or 21 days after laser therapy. The light dose 20 J/cm2 and 40 J/cm2 together with the used ALA dose caused no reduction in bladder capacity, whereas 80 J/cm2 light dose produced up to 50% reduction in the capacity at 3 weeks postoperatively. In control group without ALA, the animals did not regain more than 34% of the capacity of their control values at 3 weeks. The light dose of 20 J/cm2 and 40 J/cm2 with ALA induced functional changes that subsided after day 1. Our results indicate that with proper dosing of photosensitizing drug and light energy, the functional impairment of urinary bladder may be reduced as transient. These findings support the use of PDT as safe therapy of superficial bladder cancer.

Two-year follow-up results of a prospective randomized trial comparing hybrid laser prostatectomy with TURP in the treatment of big benign prostates.

OBJECTIVE: We compared conventional transurethral electroresection of the prostate (TURP) and hybrid laser treatment in patients with symptomatic bladder outflow obstruction caused by a benign prostate bigger than 40 ml. MATERIAL AND METHODS: Forty-six patients with symptomatic urodynamically confirmed outflow obstruction caused by benign prostate hyperplasia bigger than 40 ml were accepted to the prospective trial and were randomized to receive hybrid laser treatment or TURP. The hybrid laser technique involved initial non-contact Nd:YAG coagulation followed by contact Nd:YAG vaporization to open the prostatic urethra. Patients were re-assessed after 3, 6, 12 and 24 months. RESULTS: Of the 46 patients, 37 (80%) were available at the 24-month follow-up. The re-operation rate was 14.3% in the hybrid laser group and 8.3% in the TURP group. The decrease in DanPSS-1 symptom score from baseline at 24 months was 51.0% in the hybrid laser group (p<0.01) and 80.0% in the TURP group (p<0.001), with no statistically significant differences between the groups. Early improvement in objective urinary parameters of peak urinary flow rate and residual urinary volume showed deterioration in hybrid laser group during longer follow-up, whereas in TURP group the improvement of these variables was sustained. Comparison between groups showed TURP to be superior in peak urinary flow rate (p < 0.001) and residual urinary volume (p < 0.01) at the 24-month follow-up visit. CONCLUSIONS: Both hybrid laser treatment and TURP give good symptomatic relief lasting at least 2 years in the treatment of big obstructing prostates, but hybrid laser treatment is associated with a higher re-operation rate because of inadequate initial prostate tissue removal and with inferior outcome in objective urinary parameters compared with TURP.

The effect of transurethral needle ablation on symptoms of chronic pelvic pain syndrome--a pilot study.

OBJECTIVE: We evaluated the effects of transurethral needle ablation (TUNA) in chronic pelvic pain syndrome (CPPS). MATERIAL AND METHODS: CPPS patients were subjected to TUNA (n = 21) or sham therapy (urethrocystoscopy) (n = 6). Digital rectal examination and transrectal ultrasound were performed. Prostate-specific antigen and urine were analysed before and 1 month after treatment. Symptoms, the DAN-PSS-1 questionnaire, urine flow, residual urine volume, medication and a subjective estimation of the effect of treatment were evaluated during a follow-up period of 12 months. RESULTS: In both groups the maximal urine flow increased and the DAN-PSS-1 score decreased, but the decrease in the DAN-PSS-1 score was significant (p = 0.002) only in the TUNA group. The total symptom score decreased from 14 to 8.3 points in the TUNA group, and from 12.6 to 8.0 points in sham patients. TUNA relieved pain significantly. In the TUNA group symptoms were ameliorated in patients with small (< or = 20 ml; p = 0.002) and large prostates (> 20 ml; p = 0.04). Similarly, patients with both mild (p = 0.004) and severe (p = 0.02) symptoms at baseline benefitted from TUNA. Of the TUNA patients, 72% felt better at 1-year follow-up, although 57% still had symptoms and 38% needed medication. The figures in the sham group were 50%, 66% and 50%, respectively. CONCLUSIONS: TUNA relieved symptoms in CPPS patients for at least 12 months. The need for medication and the presence of symptoms were reduced, and the fraction of patients satisfied with treatment was higher in the TUNA group than in the sham group. However, these differences between the groups were not statistically significant. To assess the clinical value of TUNA in CPPS a prospective double-blind study with a large number of patients is needed to confirm the results of this pilot study.

Human complement factor H related protein test for monitoring bladder cancer.

PURPOSE: The BTA stat test is a rapid, noninvasive, qualitative urine test that detects bladder tumor associated antigen (human complement factor H related protein) in urine. We compared BTA stat test to voided urine cytology in patients monitored for bladder cancer in a prospective trial, and determined whether this test is effective in detection of recurrence not seen by regular cystoscopy. MATERIALS AND METHODS: A total of 445 consecutive patients with bladder cancer were studied. A voided urine sample was obtained before cystoscopy and divided for culture, cytology and BTA stat testing. In cases of a positive BTA stat test but negative cystoscopy, excretory urography or renal ultrasound, random biopsies and collected ureteral urine samples for ureteral cytology were obtained. The overall sensitivity and specificity as well as positive and negative predictive values for BTA stat test, cytology and their combination were calculated. RESULTS: Of the 445 patients 118 (26.5%) had bladder cancer recurrence on cystoscopy, which was detected by BTA stat test and cytology in 63 (53.4%) and 21 (17.8%), respectively. Of the remaining 327 patients not having recurrent tumor on cystoscopy 81 (24.8%) had a positive BTA stat test. Excretory urography or renal ultrasound and random biopsies in 48 (59.3%) of these patients revealed 7 recurrences, making the total number of recurrent tumors 125 of 412 (30.3%). The overall sensitivities and specificities for the BTA stat test, cytology and their combination were 56.0%, 19.2%, 60.0% and 85.7%, 98.3% and 85.0%, respectively. CONCLUSIONS: The sensitivity for detection of recurrent tumor on BTA stat test is superior to that of voided urine cytology in all bladder cancer categories, whereas the specificity of voided urine cytology is higher than that for BTA stat test. However, a sixth of the patients with apparent false-positive BTA stat test results chosen for further investigation had recurrent tumors that were not found on routine cystoscopy. Although the sensitivity and specificity were highest when both tests were used, the differences were not significant overall. Therefore, the BTA stat test could potentially replace urine cytology for followup of superficial bladder cancer.

Expression and prognostic value of CD44 standard and variant v3 and v6 isoforms in prostate cancer.

BACKGROUND: The adhesion molecule CD44 standard (CD44s), and its variant isoforms v3 and v6 are associated with cell-to-cell adhesion. The down-regulation of CD44 standard and its variant isoform CD44v6 is linked with early cancer cell dissemination, but the relationship between CD44v3 and malignant features of prostate cancer (PC) has not been established previously. METHODS: The expression of CD44s and its CD44v3 and CD44v6 isoforms was analysed by immunohistochemistry in 209 archival PC biopsy specimens to establish their prognostic value. RESULTS: Down-regulation of CD44s and CD44v6 was related to high T classification, metastasis, high Gleason score, DNA aneuploidy, high S-phase fraction, high mitotic index, perineural growth and dense amount of tumour infiltrating lymphocytes (p < 0.03 for all). Down-regulation of CD44s and CD44v6 was related to poor survival in the entire cohort (p < 0.0001), in M0 tumours (p < 0.001) and in T1-2M0 tumours (p < 0.05). In needle biopsies and TURP specimens, the prognostic impact of the investigated parameters was similar. In the multivariate analysis, T classification (p = 0.0009), presence of metastases (p < 0.0001), Gleason score (p = 0.0060) and CD44v6 (p = 0.0220) expression were independent prognostic factors. In M0 tumours, T classification (p < 0.0001) and CD44v6 (p = 0.003) independently predicted survival. CONCLUSION: Down-regulation of CD44s and its CD44v6 isoform is related to tumour malignancy and unfavourable prognosis in PC.

MR urography in evaluation of acute flank pain: T2-weighted sequences and gadolinium-enhanced three-dimensional FLASH compared with urography. Fast low-angle shot.

OBJECTIVE: The aim of this study was to compare the usefulness of breath-hold heavily T2-weighted sequences with gadolinium-enhanced three-dimensional fast low-angle shot (3D FLASH) MR urography in the evaluation of patients with acute flank pain. SUBJECTS AND METHODS: Forty consecutive patients with symptoms of acute flank pain underwent MR urography followed immediately by excretory urography. Heavily T2-weighted (combined thin-slice half-Fourier acquisition single-shot turbo spin-echo [HASTE] and thick-slab single-shot turbo spin-echo) and 3D FLASH sequences were evaluated separately and independently by two experienced radiologists for the presence, cause, level, and degree of obstruction. Interobserver agreement was calculated using the kappa statistic. Excretory urography and the final clinical diagnosis were used as reference. RESULTS: Twenty-six patients were found to have unilateral obstruction caused by ureteral stones. Both MR urography methods were excellent for detecting obstruction. In the detection of stones 3D FLASH was superior, with a sensitivity of 96.2% and 100% and specificity of 100% and 100% for observers A and B, respectively, compared with a sensitivity of 57.7% and 53.8% and a specificity of 100% and 100%, respectively, for T2-weighted sequences. The best degree of obstruction was seen with 3D FLASH, and the interobserver agreement was excellent for stone detection (kappa = 0.97). CONCLUSION: T2-weighted sequences alone are not sufficient for examining patients with acute flank pain. However, the combined use of both T2-weighted and 3D FLASH sequences will ensure better confidence in the evaluation of acute suspected renal colic. MR urography can replace conventional excretory urography when the latter is contraindicated or undesirable.

A randomized trial of the choice of treatment in prostate cancer: design and baseline characteristics.

OBJECTIVE: To assess the effects of different approaches to decision-making on the treatment chosen for prostate cancer and on the patients' quality of life in prostate cancer. PATIENTS AND METHODS: A multicentre randomized trial was conducted, including all histologically confirmed cases of prostate cancer diagnosed between September 1993 and November 1994 in four Finnish hospitals. In the intervention group, the role of the patient in the choice of treatment was actively emphasized. In the control group, the treatment was chosen using standardized treatment protocols. The first intermediate endpoint was the patient's participation in decision-making and the next will be the treatment chosen in the intervention and control groups. The main outcome will be the quality of life. Clinical data on prognostic factors including age, tumour grade, stage, functional status and serum prostate-specific antigen (PSA) concentration was collected for comparison between the arms, and between those enrolled or not. RESULTS: In all, 210 of 251 eligible patients were randomized into the two arms. Patients were randomized before obtaining informed consent, which led to four patients already randomized refusing to participate. The 41 patients not enrolled were of similar age and grade distribution, but more frequently had extensive disease than had those enrolled in the trial. Three patients were unable to participate because of rapid deterioration in their general condition after randomization. There were no clear differences in baseline characteristics (including age, functional status, tumour grade and stage) of the patients between the arms. The distribution of PSA level differed slightly between the arms, which may require adjustment in the analyses. Patients in the intervention arm participated in decision-making more actively than those in the control arm. CONCLUSION: Randomized studies on ethical issues such as the patient's role in choosing treatment are feasible and likely to provide important information.

Evaluation of p21WAF1/CIP1 and cyclin D1 expression in the progression of superficial bladder cancer. Finbladder Group.

Immunoreactivity of p21WAF1/CIP1 and cyclin D1 proteins was assessed in a cohort of 207 patients with superficial (pTa-pT1) bladder cancer followed up for a mean of 4.9 years. The results of the immunostainings were compared with T category, WHO grade, tumor cell proliferation rate (MIB-1 score), the expressions of p53 and bcl-2 as well as survival. Sixty-eight percent and 75% of the tumors were p21WAF1/CIP1 positive (> or = 5% of cells positive) and cyclin D1 positive (> or = 10% of cells positive), respectively. The p21WAF1/CIP1 expression was related to cyclin D1 immunolabelling (P < 0.001) but not to the other variables studied. The expression of cyclin D1 was inversely associated with T category (P = 0.001), WHO grade (P = 0.006), MIB-1 score (P = 0.014), p53 expression (P = 0.001), and bcl-2 (P = 0.011) immunoreactivity. In univariate analysis, T category (P = 0.0001), WHO grade (P < 0.0001), MIB-1 score (P < 0.0001), bcl-2 (P = 0.0092), p53 (P = 0.0016) and p21WAF1/CIP1 (P = 0.009) expressions were significant prognostic factors with regard to tumor progression, whereas cyclin D1 was without any prognostic significance (P = 0.1). Out of 123 p21 positive tumors 21 progressed, whereas only 2 out of 58 p21 negative tumors progressed. In multivariate analysis, the MIB-1 score was the only independent predictor of cancer-specific survival (P = 0.03), whereas tumor grade (P = 0.002) and cyclin D1 expression (P = 0.04) were independent predictors of tumor recurrence. Only the WHO grade (P = 0.04) retained its prognostic value indicating the risk of progression. We suggest that in superficial bladder cancer p21WAF1/CIP1 and cyclin D1 immunohistochemistry provide no additional prognostic information compared with already established prognostic factors for predicting the risk of progressive disease.

Prognostic value of CD44 standard, variant isoforms 3 and 6 and -catenin expression in local prostate cancer treated by radical prostatectomy.

OBJECTIVE: The clinical and histological data of prostate cancer patients were compared with the expression of CD44 standard (CD44s), variant isoforms CD44v3, CD44v6 and alpha-catenin. The prognostic value of these adhesion molecules was also analysed. PATIENTS AND METHODS: We analysed the clinical and histological data of 87 prostate cancer patients treated by radical prostatectomy in two Finnish hospitals. The mean (SD) age of the patients at diagnosis was 64 years (6) and the mean follow-up was 3 years (8). Immunohistochemistry was used to detect the expression of CD44s and its v3 (CD44v3) and v6 (CD44v6) isoforms and alpha-catenin. RESULTS: The mean (SD) fractions of positively stained cancer cells were 38 (38), 10 (22), 56 (41) and 93% (17) for CD44s, CD44v3, CD44v6 and alpha-catenin, respectively. Low fractions of CD44s- and CD44v6-positive cancer cells were related to high preoperative prostate-specific antigen (PSA) levels (p<0.05 for both). Low fraction of CD44s positive cancer cells was linked with presence of seminal vesicle invasion (p = 0.07), surgical margin positivity (p = 0.09), high Gleason score (p = 0.04) and high mitotic index (p = 0. 02). Low fraction of CD44v3-positive cancer cells was related to positive surgical margins (p = 0.05), high Gleason score (p = 0.04), presence of perineural infiltration (p = 0.02) and absence of tumour-infiltrating lymphocytes (p = 0.02). Low fraction of CD44v6-positive cancer cells was related to high pT classification (p = 0.07), capsule invasion (p = 0.03), positive surgical margins (p = 0.05), high Gleason score (p = 0.008), perineural infiltration (p = 0.0001) and high mitotic index (p = 0.001). alpha-Catenin expression was not related to any of the clinicopathological variables included in this study. Gleason score (p = 0.001), pT classification (p = 0.007), perineural infiltration (p = 0.01) and the fraction of CD44v3-positive cancer cells (p = 0.04) were predictors of PSA failure in univariate analysis. pT category (p = 0. 012), Gleason score (p = 0.02) and expression of CD44v3 (p = 0.0003) were independent predictors of PSA failure. CONCLUSIONS: The expression of CD44s, CD44v3 and CD44v6 is related to tumour differentiation. The expression of CD44v3 independently predicts PSA failure in addition to Gleason score and pT category during a short-term follow-up.

The morphological, in situ effects of a self-reinforced bioabsorbable polylactide (SR-PLA 96) ureteric stent; an experimental study.

PURPOSE: The present study was done to evaluate the biocompatibility of a new biodegradable double helical spiral self-reinforced poly-L, D-lactide copolymer (L/D ratio 96/4, SR-PLA96) ureteric stent. MATERIALS AND METHODS: In sixteen dogs, the right ureter was cut transversally, sutured and stented with a 50 mm. long SR-PLA 96 stent. In eight dogs, left ureter was similarly operated and stented with a double-J pigtail stent (C-Flex, Cook Urological Inc.), while eight remaining ureters served as plain controls. Urine was analyzed for signs of infection. The dogs were terminated at 6, 12 and 24 weeks postoperatively and the ureters dissected to find persistent SR-PLA 96 particles or local ureteric changes. Histologic samples were taken at three levels of dissected ureters in contact with the stent. RESULTS: C-Flex and SR-PLA 96 materials were well tolerated. Both of these induced only minimal ureteral wall edema, epithelial hyperplasia, epithelial destruction and inflammatory cell reaction. In SR-PLA 96 stented ureters the tissue reaction subsided after the degradation of the device. CONCLUSIONS: SR-PLA 96 spiral stent is regarded highly compatible and SR-PLA 96 might be a suitable material for a partial ureteric stent. Biodegradation of a SR-PLA 96 stent makes stent removal unnecessary.

The prognostic value of inducible nitric oxide synthase in local prostate cancer.

OBJECTIVE: To compare the clinical and histological data from patients with prostate cancer with the results of the immunohistochemical analysis of inducible nitric oxide synthase (iNOS), and thus determine the prognostic value of iNOS. PATIENTS AND METHODS: The study included 82 patients (mean age 64.6 years, SD 6.1) with local prostate cancer treated by radical prostatectomy in two Finnish hospitals. Their mean (SD) follow-up was 3.3 (2.2) years. An immunohistochemical method was used to detect the expression of iNOS in these specimens, and the expression graded according to staining intensity as none, weak or strong. RESULTS: There was weak or strong expression of iNOS in 25 (31%) and 56 (68%) of the patients, respectively, and one specimen was negative for iNOS. Strong expression of iNOS was related to high a preoperative prostate specific antigen (PSA) level (P = 0.006) and high pT classification (P < 0.001), but not to nodal status, grade, seminal vesicle or capsular invasion, surgical margin status, perineural infiltration, tumour infiltrating lymphocytes or proliferation rate of cancer cells. A PSA failure was detected in 29 patients but was not predicted by iNOS expression. A Cox multivariate analysis showed that surgical margin positivity, seminal vesicle involvement and number of tumour infiltrating lymphocytes predicted the PSA failure. CONCLUSION: A high expression of iNOS was related to a high pT classification and the preoperative PSA level but not to other established prognostic factors; iNOS expression was not a predictor of PSA failure in patients with local prostate cancer.

Characterization of a new animal model for human renal cell carcinoma.

BACKGROUND: Human renal cell carcinoma (RCC) is the most common kidney malignancy with significant mortality. Human tumor xenograft models are important tools for cancer research. MATERIALS AND METHODS: We have established and characterized a new animal model for human RCC using Caki-2 cells implanted into the renal subcapsule (RSC) of nude mice. Histology, immunocytochemistry, in situ hybridization and magnetic resonance imaging (MRI) were used to analyze the tumors. RESULTS: The implantations generated reproducible carcinomas which closely resemble human RCC. The tumors showed cystic-papillary structures, rich capillary network and fibro-septa formations. Proliferation varied from 0-5% and from 1-60% in cystic and solid areas, respectively. Apoptosis was less than 1%. Macrophages and other inflammatory cell infiltrations were detected in the tumors. VEGF-A and angiopoietin I were expressed in a small number of cells in large tumors. Tumors did not metastasize outside peritoneal cavity. Survival of the tumor bearing animals was 23 +/- 3 weeks. CONCLUSIONS: It is concluded that Caki-2 carcinomas implanted into renal subcapsule of nude mice resemble human RCC in several aspects and represent a good animal model for studies regarding the pathogenesis and treatment of human RCC.