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.

Urethral strictures in childhood.

Thirty-six children have been treated for a non-hypospadiac urethral stricture. Of 12 patients with meatal or submeatal stenosis, 10 had undergone circumcision for balanitis xerotica obliterans. The strictures were successfully treated by meatoplasty or meatal dilatation. Twenty-four children had a more proximal urethral stricture: 16 were caused by urethral catheterisation, 4 were post-traumatic, 2 were congenital and 2 were idiopathic. Sixteen children were treated by visual urethrotomy; this was successful in 12 after a maximum of 2 urethrotomies. Two children required 4 or more urethrotomies and 2 required urethroplasty for restricturing. Seven children were treated by a formal urethroplasty. There were no complications. Two patients died of unrelated medical conditions. Follow-up was for a mean of 2 years.

Preferential and novel activation of H-ras in human bladder carcinomas.

In a survey of primary human bladder carcinomas from 24 patients, using the NIH/3T3 transfection nude mouse tumor assay, we have detected an activated c-H-ras-1 gene in four cases. Two of these scored negative in primary transfections using a NIH/3T3 focus assay. Oligonucleotide analysis of genomic and enzymatically amplified DNA revealed substitution of valine at codon 12 in DNA from three transfectants and their parental carcinomas, which was absent from the DNA of normal tissue of each of these patients. The fourth activation was identified as a cysteine substitution at codon 13, a novel activation of c-H-ras-1 in a solid tumor sample. Thus, all seven activated ras genes reported in human urothelial tumors (Fujita et al., Proc. Natl. Acad. Sci. USA 82, 3849-3853, 1985) have been c-H-ras-1 genes, strongly suggesting that this member of the ras gene family is preferentially activated in cells of transitional origin.

Who needs a prostatectomy? Review of a waiting list.

A total of 118 patients on a waiting list for a transurethral prostatectomy, who had been selected primarily on the basis of their symptoms and the finding of an enlarged prostate, were reassessed by objective tests. Of the 107 finally studied, 44% were retained on the waiting list and a further 8% kept under review; 48% were discharged from any further follow-up. The study reinforces the importance of objectively assessing patients presenting with urinary symptoms.

The management of obstructive renal candidiasis in the neonate.

Neonatal renal candidiasis is a rare complication of prematurity associated with a mortality rate of 50%. We describe a patient who was treated by nephrostomy drainage together with the removal of the fungal debris and both systemic and local antifungal therapy. The infection was eradicated and the baby survived with minimal renal morbidity. A rational plan of treatment is presented which may help to reduce the mortality rate in future.

Is the conservative management of chronic retention in men ever justified?

OBJECTIVE: To assess the outcome of men presenting with lower urinary tract symptoms (LUTS) associated with large postvoid residual urine volumes (PVR). PATIENTS AND METHODS: The study included men presenting with LUTS and a PVR of > 250 mL who, because of significant comorbidity, a low symptom score or patient request, were managed conservatively and prospectively, and were followed with symptom assessment, serum creatinine levels, flow rates and renal ultrasonography. Patients were actively managed if there was a history of previous outflow tract surgery, prostate cancer, urethral strictures, neuropathy, elevated creatinine or hydronephrosis. In all, 93 men (mean age 70 years, range 40-84) with a median (range) PVR of 363 mL (250-700) were included in the study and followed for 5 (3-10) years. At presentation, the median maximum flow rate was 10.2 (3-30) mL/s and the voided volume 316 (89-714) mL. RESULTS: The measured PVR remained stable in 47 (51%), reduced in 27 (29%) and increased in 19 (20%) patients; 31 patients (33%) went on to transurethral resection of the prostate after a median of 30 (10-120) months, because of serum creatinine elevation (two), acute retention (seven), increasing PVR (eight) and worsening symptoms (14). Of 31 patients 25 were available for evaluation after surgery; their median PVR was 159 (0-1000) mL, flow rate 18.4 (4-37) mL/s and voided volume 321 (90-653) mL. Symptoms were improved in all but five men. There was no difference in initial flow rate, voided volume or PVR between those who developed complications or went on to surgery and those who did not. Urinary tract infections (UTIs) occurred in five patients and two developed bladder stones. CONCLUSIONS: Complications such as renal failure, acute retention and UTIs are uncommon in men with large, chronic PVRs. Conservative management for this group of patients is reasonable but outpatient review is prudent. There were no factors that could be used to predict those patients who eventually required surgery.

The outcome of antenatally diagnosed urological abnormalities.

Twenty-eight patients undergoing routine antenatal screening by ultrasound were found to have a fetus with a major urological abnormality. In addition, two babies suspected of having an enlarged bladder were found post-natally to be normal. Seven of the 28 pregnancies were terminated before 26 weeks' gestation as a result of the ultrasound findings and all these fetuses had lethal renal abnormalities. Of the remaining 21 babies, four died of renal failure following delivery. Fifteen of the 17 babies who are alive and well had an ultrasound scan before 24 weeks' gestation. Only one of these scans revealed the abnormality. In the remaining patients the abnormality was first detected after 28 weeks. No patient had surgery in utero. Our data suggest that renal abnormalities detected prior to 24 weeks' gestation are associated with severe renal impairment. It appears that the role of antenatal drainage procedures may be of limited value.

Double J stents. A review of 100 patients.

Double J stents have been advocated for drainage or splintage of the ureter. One hundred and thirty-eight attempts at stent insertion were made in 100 patients. In 78% of attempts the stent was satisfactorily placed. Their use in retroperitoneal fibrosis, ureteric trauma and acute hydronephrosis of pregnancy has been encouraging. Poor results have been obtained in patients with malignant obstruction or tuberculous stricture.

Contemporary results of radical radiotherapy for bladder transitional cell carcinoma in a district general hospital with cancer-centre status.

OBJECTIVE: To assess the current efficacy and safety of definitive external beam radiotherapy (EBRT) in the treatment of invasive bladder transitional cell carcinoma (TCC) in a district general hospital with cancer-centre status. PATIENTS AND METHODS: The case notes of all patients with bladder TCC undergoing EBRT with curative intent over an 8-year period (1988-95) were reviewed. Additional missing outcome data were collected. RESULTS: In all, 120 patients (109 men; median age 70 years, range 34-90) underwent radical EBRT (40-65 Gy; fraction median=20) over the 8-year period. Staging, as assessed by examination under anaesthesia and computed tomography, was T1 in 16%, T2 in 43%, T3 in 38% and T4 in 3%. In 96 patients (80%) the tumour was poorly differentiated (G3). The overall morbidity at 12 months was 12%; proctitis occurred in nine patients (8%) and cystitis in five (4%). Sixty-seven patients (59%) developed a local recurrence and in 36 (30%) this was invasive. The overall median survival was 60 months. Thirty-three patients underwent salvage cystectomy with a subsequent median survival of 12.5 months. CONCLUSION: Modern radical multifraction EBRT in invasive bladder TCC has a low morbidity, with an overall median survival of 5 years.

Potential value of antisera to epithelial membrane antigen in detecting early invasion in transitional cell carcinoma.

The distribution of epithelial membrane antigen in human transitional epithelium using immunocytochemical techniques was investigated. In normal urothelium the antigen is restricted to the luminal surface and superficial cell cytoplasm. During neoplastic progression cytoplasmic staining of intermediate and basal cells is seen. In certain circumstances staining is seen at the interface between the stroma and tumour. The latter appearance correlates with the presence of invasion as assessed by conventional histology and may help to identify early invasion in difficult cases.

Response to aminoglutethimide and cortisone acetate in advanced prostatic cancer.

Forty patients with metastatic adenocarcinoma of the prostate were evaluated for response to treatment with aminoglutethimide plus cortisone acetate. All had relapsed from or failed to respond to primary endocrine treatment with orchidectomy or stilboestrol. Nineteen patients (48%) showed subjective response, in most cases relief of bone pain. Side effects limited treatment in only 3 patients. We conclude that aminoglutethimide plus cortisone acetate is a useful addition to the treatment available for this difficult group of patients. The mechanism by which this treatment has a beneficial effect remains unclear.

Prognostic factors in non-infiltrating carcinoma of the bladder: a preliminary report.

We have reviewed 111 patients with papillary transitional cell carcinoma of the bladder, category Ta and T1, admitted between 1975 and 1980. Histological grade and the presence of multiple tumours at presentation were the most useful prognostic features in terms of recurrence and mortality from either locally invasive or metastatic disease.