Hand pattern indicates prostate cancer risk.

BACKGROUND: The ratio of digit lengths is fixed in utero, and may be a proxy indicator for prenatal testosterone levels. METHODS: We analysed the right-hand pattern and prostate cancer risk in 1524 prostate cancer cases and 3044 population-based controls. RESULTS: Compared with index finger shorter than ring finger (low 2D : 4D), men with index finger longer than ring finger (high 2D : 4D) showed a negative association, suggesting a protective effect with a 33% risk reduction (odds ratio (OR) 0.67, 95% confidence interval (CI) 0.57-0.80). Risk reduction was even greater (87%) in age group <60 (OR 0.13, 95% CI 0.09-0.21). CONCLUSION: Pattern of finger lengths may be a simple marker of prostate cancer risk, with length of 2D greater than 4D suggestive of lower risk.

Diagnostic radiation procedures and risk of prostate cancer.

Exposure to ionising radiation is an established risk factor for many cancers. We conducted a case-control study to investigate whether exposure to low dose ionisation radiation from diagnostic x-ray procedures could be established as a risk factor for prostate cancer. In all 431 young-onset prostate cancer cases and 409 controls frequency matched by age were included. Exposures to barium meal, barium enema, hip x-rays, leg x-rays and intravenous pyelogram (IVP) were considered. Exposures to barium enema (adjusted odds ratio (OR) 2.06, 95% confidence interval (CI) 1.01-4.20) and hip x-rays (adjusted OR 2.23, 95% CI 1.42-3.49) at least 5 years before diagnosis were significantly associated with increased prostate cancer. For those with a family history of cancer, exposures to hip x-rays dating 10 or 20 years before diagnosis were associated with a significantly increased risk of prostate cancer: adjusted OR 5.01, 95% CI 1.64-15.31 and adjusted OR 14.23, 95% CI 1.83-110.74, respectively. Our findings show that exposure of the prostate gland to diagnostic radiological procedures may be associated with increased cancer risk. This effect seems to be modified by a positive family history of cancer suggesting that genetic factors may play a role in this risk association.

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.

Monoclonal antibodies reacting with colorectal tumours.

25 mouse monoclonal antibodies were screened for cell surface reactivity with colorectal tumours using the indirect immunoperoxidase method. Five antibodies of the IgG subclasses were selected. LICR-LON-M8 was raised against human milk fat globule membrane (HMFGM). The remaining four antibodies 48-1, 3-48-2, 77-1, and 8-30-3 were raised against human bladder metastases. M8, 77-1, and 8-30-3 which showed epithelial membrane antigen (EMA) - like reactivity exhibited greater selectivity for colorectal cancer compared with normal colon. M8 and 77-1 are being evaluated for immunoscintigraphy of colorectal carcinoma.

Statistical basis of the Compton metabolic profile test.

The statistical basis of the Compton metabolic profile test is described and alternative methods for choosing animals for blood sampling are discussed. Recent modifications to the presentation of results, which facilitate interpretation, are described.

Brachytherapy for advanced prostate cancer bleeding.

Advanced prostate cancer patients frequently deal with intractable prostatic bleeding which is a difficult problem to manage. Intraurethral high-dose rate (HDR) brachytherapy may palliate this condition. Advanced prostate cancer patients with intractable prostatic bleeding were offered brachytherapy with Iridium-192 using a Micro-selectron HDR machine. During a 5-year period, analysis was performed in 23 patients with a median age and Gleason score of 78 years and 9, respectively. Following brachytherapy, haematuria resolved in 19 of the 23 patients and was recurrence free at 6 months. Intraurethral HDR brachytherapy is a potentially effective modality for treating haematuria in patients with advanced prostate cancer.

Complications of ear disease.

Forty-seven patients with acute mastoiditis were treated in our hospital over a 2 and a half year period. Seven patients were symptomatic for a short period only. The other 40 gave a history of chronic ear disease, 22 of them with cholesteatoma. Post auricular swelling is an important sign of acute mastoiditis but was found in only 64% of the patients. Forty-five percent of our patients were found to have infection spread beyond the mastoid. Meningitis was the most common complication (13 patients). Most of the patients who presented without post auricular swelling were diagnosed as a result of having one or more complications. We believe that in cases of intracranial pathology or septic fever associated with ear disease, the diagnosis of mastoiditis is most likely. Early operation combined with appropriate antibiotic treatment can prevent further complications and fatal outcome.

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.

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.

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.

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.

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.

A dose-ranging study of the efficacy and safety of tamsulosin, the first prostate-selective alpha 1A-adrenoceptor antagonist, in patients with benign prostatic obstruction (symptomatic benign prostatic hyperplasia).

OBJECTIVE: To evaluate the efficacy and safety in a dose-ranging study of tamsulosin (once-daily) as a modified-release formulation compared with placebo in patients with lower urinary tract symptoms (LUTS) associated with benign prostatic obstruction (BPO), and to establish the optimum dosage for phase III clinical studies. PATIENTS AND METHODS: Of 169 patients with LUTS associated with BPO enrolled in a 3 week placebo run-in period, 126 were subsequently randomized to receive placebo (28), or 0.2 mg (35), 0.4 mg (30), or 0.6 mg (33) of tamsulosin once daily for 4 weeks. Free-flow and pressure-flow measurements, and modified Boyarsky symptom scores were used to determine efficacy. Safety was evaluated by monitoring adverse events and vital signs (including 8 h after the first dose), and by laboratory determinations. RESULTS: Tamsulosin 0.4 mg and 0.6 mg produced significantly greater improvements in maximum urinary flow rate (Qmax) (2.2 mL/s, 22.6%, and 1.8 mL/s, 20.2%, respectively) than did placebo (-0.1 mL/s, -0.9%). The results from the pressure-flow studies confirmed the results for Qmax in the free flow studies, with optimum and significant effects for tamsulosin 0.4 mg. This also applied for detrusor pressure at maximum flow, which decreased by 26.6 cmH2O (-28.2%) on 0.4 mg tamsulosin whereas it increased by 4.9 cm H2O (5.7%) on placebo. The greatest reductions in total symptom score were obtained with tamsulosin 0.4 mg and 0.6 mg (4.1, -28.7%, and 4.4 points, -28.2%, respectively) compared with reductions of 3.4 (-20.1%) in the tamsulosin (0.2 mg) and 2.9 points (-17.7%) in the placebo groups. The difference in effects on total symptom score between treatment groups was not statistically significant, which can be attributed to the small sample size. Tamsulosin was well tolerated; at least one adverse event was reported by 29%, 23%, 27% and 36% of patients in the placebo and tamsulosin 0.2 mg, 0.4 mg and 0.6 mg groups, respectively. There were no apparent tamsulosin dose-dependent changes in vital signs from baseline to the end of 4 weeks of randomized treatment. Tamsulosin caused no statistically significantly greater changes in blood pressure than placebo during the initial 8 h after the first dose. There were no clinically significant changes in laboratory variables. CONCLUSION: Tamsulosin is well tolerated and effective in improving urinary flow and relieving LUTS associated with BPO. Optimal effects are achieved with tamsulosin 0.4 mg administered once daily.

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.

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.

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.

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.

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.