Monoclonal antibodies raised against cell membrane components of human bladder tumor tissue recognizing subpopulations in normal urothelium.

Monoclonal antibodies to human bladder carcinoma membrane antigens were produced by fusion of MOPC-21 NS/1 mouse myeloma cells with spleen cells from BALB/c mice immunized against a crude membrane extract from a metastatic bladder carcinoma. Hybrids were screened for antibody production in a solid-phase radioimmunoassay and selected for their reactivity with subpopulations of urothelial cells on normal bladder tissue sections. Three antibody groups were defined: Group I (4-72-2) was urothelium specific and stained the basal and intermediate cells in normal urothelium; group II (3-48-2, 48-1, and 3-50-3) showed reactivity with intermediate and superficial cells; group III (8-30-3, 77-1, 2-94-2, 3-71-1, and 94-3) was restricted to antigens on the luminal membrane of superficial cells. All antibodies recognized antigenic determinants in fixed paraffin-embedded material and within groups showed a range of staining patterns in other tissues. Studies on sections representing different stages of neoplastic progression showed disruption in the antibody-staining pattern in urothelium and, in all cases, a strong distinct staining of invasive tumor areas and metastatic secondary tumors. Biochemical analysis of the antigens defined at least three antigenic systems, two of which consisted of molecules having Mr of 250,000 and 300,000 as judged by Western blot analysis. Antigenic determinants recognized by some antibodies (3-48-2, 48-1, 3-50-3, 8-30-3, 77-1, and 3-71-1) were shown to be carbohydrate by reactivity with glycolipid fraction and suggest that antibodies within groups recognize different epitopes on the same molecule.

The frequency of germ-line mutations in the breast cancer predisposition genes BRCA1 and BRCA2 in familial prostate cancer. The Cancer Research Campaign/British Prostate Group United Kingdom Familial Prostate Cancer Study Collaborators.

Predisposition to prostate cancer has a genetic component, and there are reports of familial clustering of breast and prostate cancer. Two highly penetrant genes that predispose individuals to breast cancer (BRCA1 and BRCA2) are known to confer an increased risk of prostate cancer of about 3-fold and 7-fold, respectively, in breast cancer families. Blood DNA from affected individuals in 38 prostate cancer clusters was analyzed for germ-line mutations in BRCA1 and BRCA2 to assess the contribution of each of these genes to familial prostate cancer. Seventeen DNA samples were each from an affected individual in families with three or more cases of prostate cancer at any age; 20 samples were from one of affected sibling pairs where one was < or = 67 years at diagnosis. No germ-line mutations were found in BRCA1. Two germ-line mutations in BRCA2 were found, and both were seen in individuals whose age at diagnosis was very young (< or = 56 years) and who were members of an affected sibling pair. One is a 4-bp deletion at base 6710 (exon 11) in a man who had prostate cancer at 54 years, and the other is a 2-bp deletion at base 5531 (exon 11) in a man who had prostate cancer at 56 years. In both cases, the wild-type allele was lost in the patient's prostate tumor at the BRCA2 locus. However, intriguingly, in neither case did the affected brother also carry the mutation. Germ-line mutations in BRCA2 may therefore account for about 5% of prostate cancer in familial clusters.

Failure to void after transurethral resection of the prostate and mode of presentation.

OBJECTIVES: Contemporary audits and reviews of outcome after transurethral resection of the prostate (TURP) make little reference to failure to void following catheter removal after this operation. There have been few reports of the likelihood of a successful trial without a catheter after TURP related to mode of presentation. We report the results of a retrospective review of outcome of TURP related to mode of presentation, age, and prostate histologic findings in a consecutive series of patients in a London Teaching Hospital. METHODS: A consecutive series of 379 patients (381 TURPs) was reviewed to document the incidence of and risk factors for failure to void following initial trial without a catheter after TURP. RESULTS: Twelve percent of men failed to void after TURP on the initial trial without a catheter. In those patients presenting with lower urinary tract symptoms, there were no instances of failure to void. Ten percent of patients with acute retention (painful inability to void, urine volume less than 800 mL), 38% with chronic retention (maintenance of spontaneous voiding, bladder volume greater than 500 mL), and 44% with acute on chronic retention (painful retention, urine volume greater than 800 mL) failed to void after TURP. Only 1% of patients required management by long-term catheterization. Failure to void on catheter removal was not related to age or prostate histologic findings. CONCLUSIONS: Bladder volume at initial presentation in patients with urinary retention provides important information about the likelihood of re-establishing spontaneous voiding catheter removal following TURP. Patients should be warned that there is a significant chance of failure to void after TURP, the exact risk depending on their mode of presentation, but that most will ultimately not require a permanent indwelling catheter.

Should all patients with ureteric colic be admitted?

A two-part study was undertaken to determine if all patients with uncomplicated ureteric colic require admission. The analgesic requirements and outcome in 31 patients admitted with ureteric colic were assessed; 20/31 (64%) required no further analgesia after admission and 8/31 (26%) required only oral/rectal analgesia. In the second part of the study a protocol was introduced allowing patients with no complicating factors to be discharged directly from the A&E department. Of 58 patients seen in the A&E department, 29 were discharged for outpatient follow-up. Of these patients, 19 required no additional acute hospital treatment, five returned for further parenteral analgesia but outside the time they would have stayed in hospital under our previous protocol (ie beyond 48 h) and three returned within 48 h of their first attendance with pain which had not responded to oral analgesics. No patient discharged from A&E subsequently required intervention for obstruction or infection. We conclude that it is not necessary to admit patients with uncomplicated ureteric colic if the initial colic has been relieved and there is adequate social support.

The role of internal urethrotomy in the prevention of urethral stricture following transurethral resection of prostate.

Urethral stricture is the commonest late complication of transurethral prostatectomy. Although internal urethrotomy is widely practised to prevent structures, there are no reports of any controlled trials of the procedure. A prospective trial of internal urethrotomy, using the Otis urethrotome, in 210 consecutive transurethral prostatectomies is presented. Patients were divided into 2 groups, those undergoing urethrotomy before TUR ("Trial group") and those undergoing TUR without urethrotomy ("Control group"), and they were followed for a minimum of 6 months. The incidence of stricture in the control group was significantly greater than in the trial group (P less than 0.01). Analysis of all other variables revealed no difference between the 2 groups and it is concluded that internal urethrotomy does prevent stricture formation and that it should be undertaken routinely before transurethral resection.

An evaluation of a simple stick test for pyuria.

The results of a simple stick test for the detection of urinary leucocyte esterase are compared with the findings from conventional examination of 150 cytoscopic specimens of urine. The test was found to indicate the presence of significant numbers of white cells in urine with accuracy, and its relevance to urological surgery is discussed

Chyluria as a cause of haematuria in patients from endemic areas.

Chyluria is an unusual cause of haematuria in temperate regions and is rarely considered even when no apparent cause has been found. We report 3 Guyanese men who presented with macroscopic haematuria in whom pyelo-lymphatic fistulae were found. In none of the patients were the symptoms severe enough for surgical disconnection of the fistula to be required.

Prognostic factors in a T3 bladder cancer trial. Co-operative Urological Cancer Group.

Information on primary tumour size, status of the pelvic lymph nodes, histological type and macroscopic tumour appearance, as well as age and sex, was available at presentation for 394 patients in the Co-operative Urological Cancer Group's prospective randomised trial for T3 cancer of the urinary bladder. An apparently significant prognostic effect of age and sex was shown to be entirely consistent with the effect of natural mortality. Primary tumour size was found to be the single most powerful prognostic factor (P = 0.002), followed by nodal status (P = 0.02). These factors do not act independently. Multivariate analysis showed that 75% of the effect of all the six variables and their first order interactions could be explained by a single prognostic grouping based on tumour size and nodal status only. Three levels for this grouping are proposed: node-negative small tumour, node-negative moderate tumour and either node-positive or large tumour. The 3-year survival probabilities for the three prognostic groups were 85.7% (95% CI 57.2 and 96.4%), 60.3% (48.0 and 71.5%) and 33.3% (23.5 and 44.8%) respectively.

Post-operative retention associated with acute prostatic infarction.

Twenty-one patients with post-operative retention following unassociated surgery and requiring transurethral resection of the prostate were compared with patients with acute retention (control group). Histological evidence of acute prostatic infarction was significantly increased in the post-operative retention group. Prolonged operative hypotension was associated with acute prostatic infarction, as were smoking and pre-existing cardiovascular disease.

Role of ultrasound in the investigation of haematuria after normal intravenous urography and cystoscopy.

The initial investigation of haematuria in the adult includes intravenous urography and cystoscopy. If these investigations reveal no cause for haematuria we propose that renal ultrasound should be considered, and illustrate this with two series of patients from different hospitals (147 from St. Peter's Hospitals, 35 from St. James' Hospital, Balham, London) with primary adenocarcinoma of the kidney.

Shared care for benign prostatic hyperplasia: a feasibility study.

OBJECTIVE: To determine the proportion of patients with symptoms of urinary outflow obstruction secondary to benign prostatic hyperplasia (BPH) who could be managed in the community after assessment in a shared-care clinic (managed by nursing staff, supervised by a consultant) to which they had direct access. PATIENTS AND METHODS: A total of 127 men were referred to one consultant urologist in a 9-month period for assessment of possible urinary outflow obstruction. All were investigated using urine analysis, serum prostate-specific antigen level, urea and electrolytes, plain abdominal X-ray, renal ultrasonography and urinary flow rate. Additional investigations were undertaken as required. The proportion of men who could have been investigated in a shared-care clinic and then managed in the community was determined. RESULTS: Of 127 men, 88 (69%) were found to have uncomplicated outflow obstruction secondary to BPH; of these 49 (38%) could have been managed in the community after assessment in the shared-care clinic and a further 27 (21%) could have been managed in the community after additional investigation by a specialist. Twelve men (9%) were found to have uncomplicated outflow obstruction and chose to undergo transurethral resection of the prostate. CONCLUSION: Many men with uncomplicated outflow obstruction could be assessed in a shared-care clinic and then managed in the community. A shared-care protocol for the management of these men has now been introduced in this unit.

The effects of aminoglutethimide and hydrocortisone, alone and combined, on androgen levels in post-orchiectomy prostatic cancer patients.

Aminoglutethimide has been used in combination with hydrocortisone in patients with advanced prostatic cancer with the rationale that it causes a 'medical adrenalectomy'. Both objective and subjective responses have been recorded. We have examined the effect of AG and HC alone and in combination on plasma androgen levels throughout the day in two studies on 11 such patients. Whilst AG combined with HC led to a significant suppression of both testosterone and androstenedione levels, the suppression with HC alone was significantly greater, indicating that any beneficial clinical effects of AG in these patients is not due to its suppression of adrenal androgen secretion.

Prostatectomy: patients' perception and long-term follow-up.

We have reviewed 500 consecutive prostatectomies with a follow-up period of between 5 and 8 years; 184 surviving patients were sent a questionnaire and patients with residual urinary symptoms were interviewed, examined and a flow rate was performed. The operative mortality rate was 0.5%. Patients who presented with retention of urine had a high mortality rate in the first 3 years after the operation. Thirty-six per cent of surviving patients with chronic retention and 24% of those who underwent elective prostatectomy had residual urinary symptoms at the time of the study. Of patients who were sexually active pre-operatively, 34% felt that the operation was responsible for a deterioration in their sex lives. The incidence of retrograde ejaculation was 93%. It was concluded that prostatectomy is a safe operation with good patient acceptability. Patients with symptoms of prostatism require careful evaluation before prostatectomy and sexually active patients should be warned of the risks of impotence and decreased satisfaction due to retrograde ejaculation.

[Basic principles and initial results of adjuvant hormone therapy and irradiation of prostatic carcinoma]. / Grundprinzipien und erste Ergebnisse der adjuvanten Hormontherapie und Bestrahlung des Prostatakarzinoms.

Radiotherapy is an effective treatment for localized prostate cancer. A dose response relationship has been demonstrated for both local tumor control and complications. Reducing the volume of normal tissue treated may allow dose escalation without an increase in RT induced side effects. Androgen blockade before RT could, by reducing tumor volume, increase local control, disease-free (DFS) and overall survival in patients (pts) with prostatic adenocarcinoma. A total of 79 patients with T2-T4 prostate cancer have been treated initially with LHRH agonists and cyproterone acetate followed by radical irradiation between 1988 and 1993. The first cohort of 22 patients were monitored intensively by transrectal ultrasound and computed tomography. For each patient conformal photon beam radiotherapy and conventional treatment plans were produced and dose volume histograms compared for total volume, rectal volume, and bladder volume. Overall mean reduction of prostate volume was about 50%, and radiotherapy target volume was reduced by 37%. 53 further patients without clinical evidence of regional or distant metastases were given 3 months preradiotherapeutic hormonal cytoreduction with a short course of cyproterone acetate and LHRH. PSA level fell rapidly in most patients and after 3 months treatment the median PSA level was 1 ng/ml and 83% had PSA level 10 ng/ml. At 18 months PSA levels continued to be < 2 ng/ml in 70% of the patients. Combined modality treatment with the neoadjuvant or adjuvant androgen deprivation and conformal therapy show considerable promise as novel methods to improve the therapeutic ratio. This treatment approach may be used to explore the possibility of dose escalation in prostate cancer to enhance local control, and therapeutic randomised studies are underway to test these approaches.

Hormonal cytoreduction and radiotherapy for carcinoma of the prostate.

We report the effect on prostatic volume of the administration of the luteinising hormone-releasing hormone (LHRH) analogue goserelin in 22 patients with locally advanced carcinoma of the prostate; 20 achieved a significant reduction in volume, the median volume being 66 ml before treatment (range 40-130) and 30 ml after 17 weeks (range 13-47). If used before external beam radiotherapy (RT), volume reduction will permit smaller boost fields and thus potentially reduce adverse radiotherapy effects. In addition, reducing tumour volume before RT may lead to an increase in local control. We discuss the possible role of hormonal volume reduction in the management of prostatic cancer.

Superficial bladder cancer: timing of check cystoscopies in the first year.

We report a prospective study of 141 patients presenting for the first time with a small, solitary, non-invasive, moderately or well differentiated transitional cell carcinoma of the bladder. The pattern of recurrence in the first year was assessed and recurrence rates calculated; 80% of patients without recurrence at 3 months remained clear in the first year. There was a highly significant reduction in recurrence rates for those free of recurrence at 3 months. It has been suggested that this group should have the second check cystoscopy at 1 year and yearly cystoscopies thereafter. Our findings support that proposal.

Comparison of aromatase activity in human prostatic, testicular and placental tissues.

The aromatase enzyme was quantified by the release of tritiated water from [1 beta-3H] androstenedione. Tritiated water was released by the crude homogenates in 4 of 18 samples of benign prostatic hyperplasia tissue and one of 5 samples of prostate carcinoma tissue. However, this apparent aromatase activity was not inhibited by 4-hydroxyandrostenedione (0.5 and 5.0 microM), and none of the particulate fractions (100,000 g pellet) prepared from each of the prostatic tissues exhibited aromatase activity. Particulate fractions from rat ovary (n = 3) and human testes (n = 6) displayed significant aromatase activity (mean values of 9.9 and 0.033 nmol estrone formed/g protein/h, respectively). The testicular aromatase was inhibited by aminoglutethimide, 4-hydroxyandrostenedione and CGS 16949A with IC50 values of 6.4, 0.17 and 0.0017 microM, respectively. These are of a similar order to values obtained with the aromatase enzyme from human placental microsomes (14, 0.43 and 0.0075 microM, respectively).

Rapid processing in the management of prostatic cancer.

OBJECTIVE: To carry out rapid histological processing of prostatic biopsies for the management of patients who present with urinary retention or other urological problems, or with a suspected diagnosis of prostatic cancer. PATIENTS AND METHODS: Biopsies were taken from each of 26 patients who presented with urinary retention or other urological problems, or with a suspected diagnosis of prostatic cancer. The biopsies were processed in a Shandon Hypercenter using a 3-hour programme and were stained on a Shandon Linistainer automatic staining machine. The slides were reviewed both immediately and at weekly histopathology audit meetings. RESULTS: Results were available within 4 h of receipt of the specimen in the laboratory. One false negative, due to a sampling error at the time of biopsy, was identified. CONCLUSION: We believe that this facility is of benefit to both surgeon and patient and should be more widely available.