¹8F-fluorocholine PET/CT compared with extended pelvic lymph node dissection in high-risk prostate cancer.

PURPOSE: To compare (18)F-fluorocholine positron-emission tomography/computed tomography (PET/CT) with extended pelvic lymph node dissection (ePLND) for the detection of lymph node metastases in a large cohort of patients with high-risk prostate cancer. MATERIALS AND METHODS: Patients with prostate-specific antigen levels between 20 and 99 ng/mL and/or Gleason score 8-10 cancers, planned for treatment with curative intent following a negative or inconclusive standard bone scan, were investigated with (18)F-fluorocholine PET/CT followed by an ePLND. None of the patients received hormonal therapy prior to these staging procedures. Results for PET/CT were compared on a per-patient basis with histopathology from ePLND. Sensitivity, specificity, positive and negative predictive values were calculated. RESULTS: PET/CT detected a total of 76 suspected lymph node metastases and four suspected bone metastases in 33 (29 %) of the 112 included patients. Of these, 35 suspected lymph node metastases, only within the anatomical template area of an ePLND, were found in 21 of the patients. Histopathology of the ePLND specimens detected 117 lymph node metastases in 48 (43 %) of the 112 patients. Per-patient sensitivity, specificity, positive and negative predictive values for (18)F-fluorocholine PET/CT for lymph node metastases within the ePLND template were 0.33, 0.92, 0.76 and 0.65, respectively. Only 11 patients had lymph nodes larger than 10 mm that would have been reported by CT alone. CONCLUSIONS: (18)F-fluorocholine PET/CT detects lymph node metastases in a significant proportion of patients with high-risk prostate cancer with a high specificity, but low sensitivity.

Open-label, clinical phase I studies of tasquinimod in patients with castration-resistant prostate cancer.

BACKGROUND: Tasquinimod is a quinoline-3-carboxamide derivative with anti-angiogenic activity. Two open-label phase I clinical trials in patients were conducted to evaluate the safety and tolerability of tasquinimod, with additional pharmacokinetic and efficacy assessments. METHODS: Patients with castration-resistant prostate cancer with no previous chemotherapy were enrolled in this study. The patients received tasquinimod up to 1 year either at fixed doses of 0.5 or 1.0 mg per day or at an initial dose of 0.25 mg per day that escalated to 1.0 mg per day. RESULTS: A total of 32 patients were enrolled; 21 patients were maintained for >or=4 months. The maximum tolerated dose was determined to be 0.5 mg per day; but when using stepwise intra-patient dose escalation, a dose of 1.0 mg per day was well tolerated. The dose-limiting toxicity was sinus tachycardia and asymptomatic elevation in amylase. Common treatment-emergent adverse events included transient laboratory abnormalities, anaemia, nausea, fatigue, myalgia and pain. A serum prostate-specific antigen (PSA) decline of >or=50% was noted in two patients. The median time to PSA progression (>25%) was 19 weeks. Only 3 out of 15 patients (median time on study: 34 weeks) developed new bone lesions. CONCLUSION: Long-term continuous oral administration of tasquinimod seems to be safe, and the overall efficacy results indicate that tasquinimod might delay disease progression.

Three-month neoadjuvant hormonal therapy before radical prostatectomy: a 7-year follow-up of a randomized controlled trial.

OBJECTIVE: To describe the outcome, assessed as the level of prostate specific antigen (PSA), of a mature (more than half the events recorded) prospective randomized study with a median follow-up of 82 months of neoadjuvant hormonal therapy before radical prostatectomy, as this has been suggested to decrease the rate of positive surgical margins (i.e. provide greater potential to completely excise the tumour). PATIENTS AND METHODS: From December 1991 to March 1994, 126 patients with clinically localized prostate cancer were randomized between direct radical prostatectomy or a 3-month course of a gonadotrophin-releasing hormone analogue before surgery. The patients were followed by PSA determinations and a value of > 0.5 ng/mL used to define progression. RESULTS: The incidence of positive surgical margins decreased from 45.5% to 23.6% (P = 0.016) with hormone treatment. Despite this there was no difference in PSA progression-free survival at the last follow-up; it was 51.5% for those undergoing radical prostatectomy only and 49.8% for those who received hormonal pretreatment (P = 0.588). CONCLUSIONS: Three months of neoadjuvant hormonal therapy before radical prostatectomy offers no benefit to the patient and cannot be recommended for routine clinical use.

Splenic rupture following ESWL for a pancreatic duct calculus.

Extracorporeal shock wave lithotripsy (ESWL) is an established and extensively used treatment alternative for urinary calculi. It is also an established method of dealing with pancreatic duct calculi complementing endoscopic techniques in selected cases. Three reports of splenic injury following and probably caused by ESWL for urinary calculi have previously been published. We report a case of splenic rupture presenting with life-threatening hemorrhage 6 days after a single ESWL therapy session for pancreatic duct calculi.

Palliative radiation with a radiolabeled diphosphonate (rhenium-186 etidronate) in patients with hormone-refractory disseminated prostate carcinoma.

MATERIAL AND METHODS: The present study investigates the safety and efficacy of 2590 MBq rhenium-186 (186Re) etidronate (i.e. twice the activity normally used) administered intravenously in 15 patients with disseminated prostatic carcinoma and bone pain. RESULTS: Pain relief was observed in 11 of 14 evaluable patients (79%), 4 of whom became completely free from pain. Five of the responding patients also noted an improvement in daily activity and two found it possible to reduce or discontinue morphine medication. Pain relief occurred within one week in four patients, and within two weeks in eight of the responding patients. The mean duration of pain relief after the first course of 186Re-etidronate was 6 weeks (range 4-10). The toxicity was mild (< or = grade 2), transient, and restricted to hematological toxicity. CONCLUSIONS: 186Re-etidronate provided rapid pain-relief and had mild toxicity in most patients with disseminated hormone-refractory prostatic carcinoma, but doubling the activity did not markedly improve the efficacy.

Regressive changes and neuroendocrine differentiation in prostate cancer after neoadjuvant hormonal treatment.

BACKGROUND: We studied the extent of neuroendocrine (NE) tumor cell differentiation and its relation to regressive changes in prostate cancer after 3-month hormonal treatment. METHODS: Radical prostatectomy specimens from 103 patients, randomized to 3-month neoadjuvant LH-RH-analogue treatment (neoadjuvant group) or to surgery alone (control group), were available for analysis. The effects of hormonal treatment in terms of positive surgical margins, the degree of histopathological changes, and tumor cell proliferation were evaluated in relation to NE-differentiation assessed with antibodies against chromogranin A (CGA). RESULTS: Both the number of CGA-positive cells/cm(2) (P < 0.003) and the proportion of NE-positive tumors (P = 0.07) were greater in the neoadjuvant group than in the control group. No correlation existed between NE-differentiation and the effects of the neoadjuvant hormonal treatment; nor did NE-differentiation correlate to the decrease in serum PSA. CONCLUSIONS: Neuroendocrine differentiation in prostate cancer increases after 3 months of neoadjuvant hormonal treatment but does not correlate to the effects of hormonal treatment.

Evaluation of DNA ploidy combined with a cytometric proliferation index of imprints from core needle biopsies in prostate cancer.

OBJECTIVE: To evaluate if DNA ploidy analysis with a proliferation index (PI) derived from DNA cytometry of imprints from core needle biopsies predicts disease progression in patients with prostate cancer. METHODS: Touch imprints were done on a consecutive series of core needle biopsies taken by the same urologist from 240 patients with suspected prostate cancer, 137 (46%) of whom were found to have prostate cancer and included in the study. Scattered cells to the right of the image cytometry (ICM) ploidy-establishing peak, the S-phase fraction, and those in the G2M area of the ICM DNA histograms, were counted in percent of the total number of tumor cells, this value being designated the ICM PI. Based on previous results in archival fine needle aspiration material, the following classification was used: DNA group I, diploid tumor with a low PI; DNA group II, diploid tumor with an intermediate PI and tetraploid tumor with a low or intermediate PI, and DNA group III, diploid or tetraploid tumor with high PI and all tumors with an aneuploid pattern. RESULTS: Correlation was found to exist between DNA groups I-III and Gleason score (GS) (p < 0.0001), T-stage (p = 0.006), M-stage (p = 0.009) and disease progression (p < 0.0001). Among the 39 patients who had curative treatment and GS 5-7, the progression-free survival rate was 100% in DNA group I, as compared with only 38% in DNA group II and 55% in DNA group III within the follow-up period (p = 0.008). CONCLUSION: DNA ploidy combined with a PI derived from image cytometry of imprints from core needle biopsies yields additional prognostic information in patients with GS 5-7. Diploid tumors with a low PI (DNA group I) are associated with a low risk of disease progression.

Tumor cell proliferation in prostate cancer after 3 months of neoadjuvant LHRH analogue treatment is a prognostic marker of recurrence after radical prostatectomy.

OBJECTIVES: To evaluate tumor cell proliferation in relation to histopathologic regressive changes and failure after radical prostatectomy after a 3-month course of neoadjuvant luteinizing hormone-releasing hormone (LHRH) analogue treatment. METHODS: We evaluated slides from 103 radical prostatectomy specimens of the 111 patients participating in a randomized trial of a 3-month course of neoadjuvant LHRH analogue treatment before radical retropubic prostatectomy (n = 50) versus surgery alone (n = 53). The histopathologic regressive changes in the specimens were scored by two pathologists. Sections were stained with the anti-Ki-67 monoclonal antibody MIB-1. The proliferation index (PI) was defined as the proportion of Ki-67-positive cells in a random cell count. The patients were followed up until treatment failure or for a mean of 39 months among those without failure. RESULTS: In the neoadjuvant group, increasing histopathologic regressive changes correlated with a decrease in capsular penetration, positive surgical margins, and tumor cell proliferation but did not correlate with Gleason score in biopsies. Treatment failure was not related to the histopathologic regressive changes. In the neoadjuvant treatment group, progression-free survival was longer in the subgroup of patients with tumors with a PI less than 1.2% compared with those with tumors with a PI greater than 1.2% (P = 0.02). Multivariate analysis of PI and histopathologic and clinical features showed the PI (P = 0.002) and the pretreatment serum prostate-specific antigen level (P = 0.003) to be significant prognostic markers of failure in the neoadjuvant group. CONCLUSIONS: Tumor cell proliferation after 3 months of neoadjuvant hormonal treatment is a prognostic marker of failure after radical prostatectomy without correlation to Gleason score or the histopathologic regressive changes resulting from hormonal treatment.

Hormonal treatment before radical prostatectomy: a 3-year followup.

PURPOSE: Hormonal treatment administered before radical prostatectomy has been shown to decrease the rate of positive surgical margins. We determine whether preoperative hormonal treatment has any impact on the subsequent failure rate. MATERIALS AND METHODS: We prospectively evaluated 122 patients with stages T1bNxM0 to T3aNxM0, grades 1 to 3 prostate cancer, including 64 randomly assigned to immediate radical retropubic prostatectomy and 58 randomly assigned to radical retropubic prostatectomy preceded by 3 months of pretreatment with a gonadotropin-releasing hormone agonist. We performed intention to treat analysis on the data with failure defined as lymph node involvement, serum prostate specific antigen greater than 0.5 ng./ml., or the need for postoperative hormonal or radiation adjuvant treatment. RESULTS: The positive margin rate was 23.6 versus 45.5% in the pretreatment plus prostatectomy versus prostatectomy only groups (p = 0.016). There were 20 failures (34.5%) in the pretreatment plus prostatectomy subgroup and 26 (40.6%) in the prostatectomy only group (p = 0.48). A negative surgical margin was associated with a significantly lower risk of progression than a positive surgical margin (20.8 versus 50.0%, p = 0.0016), and progression was delayed by approximately 1 year after hormonal pretreatment. However, at a median followup of 38 months there was no difference in progression-free survival (p = 0.57). CONCLUSIONS: Although hormonal pretreatment significantly decreased the positive margin rate, it did not result in any difference in progression-free survival when followup exceeded 3 years. Thus, our current results do not support the routine administration of hormonal treatment before radical prostatectomy.

A DNA cytometric proliferation index improves the value of the DNA ploidy pattern as a prognosticating tool in patients with carcinoma of the prostate.

OBJECTIVES: A still controversial issue is whether the results of a cytometric assessment of the DNA distribution pattern of the nuclei of the neoplastic parenchymal cells of a prostatic adenocarcinoma has additional prognostic value to that of the stage and grade of the disease. To increase the accuracy of the DNA ploidy assessments. Image cytometry (ICM) has been used and combined with the determination of an ICM proliferation index (PI) to increase its value as an additional prognosticating tool. METHODS: We investigated 96 patients, followed up since diagnosis in 1980/1981 until death or, in 11 surviving patients, for an average of 14.5 years. Survival analysis was made by the conventional Kaplan-Meier method. Fine-needle aspiration biopsy was used as the major diagnostic tool. The neoplastic cell nuclei were classified as ICM DNA diploid, tetraploid, or aneuploid by means of the ploidy-establishing peak in the ICM DNA histograms, as well as the fraction of tumor cells in the S-phase. Scattered cells to the right of the ploidy-establishing peak, the S-phase fraction, and those in the G2M area of the ICM DNA histograms were counted as percent of the total number of tumor cells; this percentage was defined as the PI. Arbitrarily, tumors with a PI less than 5% were classified as having a low proliferation rate, those with a PI greater than 10% were considered highly proliferating, and those with a PI between 5% and 10% as carcinomas with an intermediate proliferation potency. RESULTS: By univariate analyses, clinical stage, cytodiagnostic grade, cytometric DNA ploidy pattern and PI all had significant prognostic value. By multivariate analyses, the PI was found to add prognostic information to that of the ICM DNA ploidy pattern variable, giving it an increase in its statistical P value from 0.002 to 0.0005. As a consequence, the combination of these two variables was found to give rise to three new patient groups with regards to their prognosis: DNA group I had tumors with a diploid ICM DNA pattern with a low PI; DNA group II had tumors with a diploid or tetraploid ICM DNA tumor cell nuclei pattern with an intermediate PI; and DNA group III had a diploid or tetraploid ICM DNA pattern with high PI and all tumors with an aneuploid pattern. By multivariate analysis, including tumor grade and clinical stage, these new DNA groups (P = 0.0004) and M stage disease (P = 0.0006) were the only significant prognostic variables. CONCLUSIONS: A DNA cytometric PI improves the prognosticating value of DNA ploidy. Patients with prostatic adenocarcinomas, classified as DNA group I, have a low risk of death from their neoplastic disease with deferred or hormonal treatment only.

Diagnosis of prostate cancer: optimal number of prostate biopsies related to serum prostate-specific antigen and findings on digital rectal examination.

The optimal number of core biopsies of the prostate that are needed for the detection of prostate cancer is unknown. A retrospective review of protocols and charts concerning 1149 transrectal ultrasound examinations with biopsy performed in 1013 patients was undertaken. Cancer detection rate was correlated to findings on digital rectal examination (DRE), serum levels of prostate-specific antigen (PSA) and number of biopsies taken. The cancer detection rate was significantly higher in patients who had five or more cores taken compared to those who had four or less (49% versus 35%, p < 0.05) in patients with serum PSA less than 10 ng/ml and a DRE suspicious of malignancy. The same trend was seen in patients with normal DRE and PSA less than 10 ng/ml (14% versus 8%, p = 0.057), while the detection rate for prostate cancer was unaffected by the number of cores taken if serum PSA was above 10 ng/ml.

Infection after transrectal core biopsies of the prostate--risk factors and antibiotic prophylaxis.

OBJECTIVE: To compare the infection rate between different durations of antibiotic prophylaxis after transrectal core biopsy and to evaluate the impact of possible risk factors. PATIENTS AND METHODS: The study comprised 491 patients who underwent transrectal core biopsies of the prostate and who were randomized to receive 400 mg of norfloxacin twice daily for one day or one week. RESULTS: Patients receiving prophylaxis for one week had a significantly lower rate of infection (4.9%) compared to patients who received only two tablets (11%; P < 0.05). The most pronounced effect was seen in those patients with risk factors (e.g. an indwelling catheter, a former history of urinary tract infection, diabetes or prostatitis) in whom the infection rate was reduced from 17.9% to 3.3% (P < 0.02), and febrile infections from 9.5% to 1.1% (P < 0.02). CONCLUSIONS: Some factors have a clear impact on the risk of developing an infection after transrectal core biopsy. Prophylaxis for one week with norfloxacin is an effective way to minimize these infections.

The risk of malignancy in the surgical margin at radical prostatectomy reduced almost three-fold in patients given neo-adjuvant hormone treatment.

OBJECTIVES: To investigate the outcome of neo-adjuvant hormone treatment before radical prostatectomy regarding local tumour extension, peri-operative blood loss and operation time. PATIENTS: Of 111 surgically treated patients with prostate cancer (T1b-T3a, N0, M0, G1-3), 55 were randomised to immediate radical prostatectomy and 56 to 3 months of neo-adjuvant treatment with triptorelin (3.75 mg i.m. every 28 days) and cyproterone acetate (50 mg b.i.d. for 3 weeks to prevent flare). RESULTS: No differences were found in blood loss or operation time but patients who had neo-adjuvant treatment had a significantly lower frequency of positive margins (41 vs. 23%, p = 0.013). CONCLUSION: Neo-adjuvant treatment does not facilitate radical prostatectomy but may improve the chance of local cure. This must, however, be documented with long-term follow-up in randomised patients.

Impaired secretory function of the prostate in men with oligo-asthenozoospermia.

The secretory function of the human prostate and the seminal vesicles is a prerequisite for gel formation and liquefaction of semen, but the relation to poor sperm motility and low sperm count in infertile men remains to be clarifyed. Our aim was to evaluate the secretory function of the prostate and the seminal vesicles in normozoospermic men (n = 35) and in asthenozoospermic men, who were all also oligozoospermic (n = 27). All 62 subjects belonged to couples undergoing routine infertility evaluation. In liquefied seminal fluid we measured the concentrations of fructose and protein C inhibitor (PCI) contributed by the seminal vesicles, PCI complexed to prostate-specific antigen (PSA), and the prostatic contribution of zinc, PSA, acid phosphatase (PAP), beta-microseminoprotein (beta-MSP), and Zn alpha 2-glycoprotein (Zn alpha 2-GP). The concentration of each prostatic secretory protein correlated significantly with that of zinc (P < 0.01) in both the normozoospermic (NZS) and oligo-asthenozoospermic (OAZS) subgroups, but the PCI concentration did not correlate significantly with that of fructose. There was no significant difference between the NZS and OAZS subgroups in ejaculate volume or secretory contribution from the seminal vesicles, whereas the OAZS subgroup was characterized by significantly lower secretory contributions of Zn alpha 2-GP (P = 0.001), Zn, PSA, PAP (P < 0.01), and beta-MSP (P < 0.05). The two subgroups did not differ significantly in the serum concentration of luteinizing hormone (LH), testosterone, or sex hormone-binding globulin (SHBG). The results thus suggest the secretory contribution of major prostatic proteins and zinc per ejaculate to be significantly decreased in oligo-asthenozoospermic men. The importance of this finding in relation to poor sperm count and motility as indicators of impaired gonadal function requires further investigation.

Renal parenchymal function evaluated by scintillation camera renography before and after pyeloplasty for hydronephrosis.

Scintillation camera renography with Tc-DTPA was performed before and after pyeloplasty on 16 kidneys with urographic signs of pelviureteric obstruction causing hydronephrosis. Regional parenchymal renograms were generated, and the passage of Tc-DTPA through the parenchyma was measured and correlated to the change in separate glomerular filtration rate. Preoperative parenchymal passage of DTPA was significantly slower (p = 0.02) in kidneys with improved glomerular filtration rate after pyeloplasty than in those without such improvement. Postoperative passage of DTPA in parenchyma was almost identical with that in a reference series. This method seems to be clinically useful for evaluating cases of hydronephrosis and for predicting the outcome of pyeloplasty.

Glomerular filtration rate up to 10 years after urinary diversion of different types. A comparative study of ileal and colonic conduit, refluxing and antirefluxing ureteral anastomosis and continent caecal reservoir.

To evaluate the influence of conduit type (ileal or colonic) and method of ureterointestinal anastomosis (refluxing or antirefluxing) on renal function in patients with urinary diversion, a prospective randomized trial was conducted in 1977-1984. During these years urinary diversion via a continent caecal reservoir emerged as an alternative to conduit diversion at our hospital, and these patients with continent reservoir were also included in the study. Total and separate glomerular filtration rate (GFR) were measured, the latter with scintillation camera renography, preoperatively and at follow-up in 70 patients. Measurements 2-10 years postoperatively showed slight to moderate decrease of GFR in all groups, with no significant difference between values according to conduit type or caecal reservoir or between refluxing and antirefluxing ureterointestinal anastomosis. Almost all of the anastomotic strictures involved the ureter that had been brought beneath the sigmoid mesentery, indicating that ischemia secondary to extensive ureteral mobilization is a likely cause of stricture in these cases.

Estimating Bacterioplankton Production by Measuring [H]thymidine Incorporation in a Eutrophic Swedish Lake.

Bacterioplankton abundance, [H]thymidine incorporation, CO(2) uptake in the dark, and fractionated primary production were measured on several occasions between June and August 1982 in eutrophic Lake Norrviken, Sweden. Bacterioplankton abundance and carbon biomass ranged from 0.5 x 10 to 2.4 x 10 cells liter and 7 to 47 mug of C liter, respectively. The average bacterial cell volume was 0.185 mum. [H]thymidine incorporation into cold-trichloroacetic acid-insoluble material ranged from 12 x 10 to 200 x 10 mol liter h. Bacterial carbon production rates were estimated to be 0.2 to 7.1 mug of C liter h. Bacterial production estimates from [H]thymidine incorporation and CO(2) uptake in the dark agreed when activity was high but diverged when activity was low and when blue-green algae (cyanobacteria) dominated the phytoplankton. Size fractionation indicated negligible uptake of [H]thymidine in the >3-mum fraction during a chrysophycean bloom in early June. We found that >50% of the H activity was in the >3-mum fraction in late August; this phenomenon was most likely due to Microcystis spp., their associated bacteria, or both. Over 60% of the CO(2) uptake in the dark was attributed to algae on each sampling occasion. Algal exudate was an important carbon source for planktonic bacteria. Bacterial production was roughly 50% of primary production.