Cytologic analysis of ureteral washings is informative in patients with grade 2 upper tract TCC considering endoscopic treatment.

OBJECTIVES: To determine the diagnostic accuracy of ureteroscopic biopsy and whether exfoliated cell cytology can improve diagnostic accuracy. METHODS: Sixty-two cases of upper tract transitional cell carcinoma were diagnosed by ureteroscopic biopsy and treated by nephroureterectomy. Stage and grade evaluation was possible in 51 cases. Cytology for exfoliated cells from the ureter/pelvis was available in 48 cases. RESULTS: Biopsies were staged as Tis in 3, Ta in 35, and T1 in 13 and graded as G1 in 6, G2 in 32, and G3 in 13. Cytology was positive/suspicious in 40% (19 of 48). The biopsy grade accurately predicted the pathologic grade (P <0.0001) and stage (P = 0.001). The biopsy stage was not associated with the final stage (P = 0.112, Fisher's exact test). Biopsy G3 accurately predicted high-grade (G3) transitional cell carcinoma in 92% (12 of 13) of cases. The remaining 1 case was G2 by final histologic examination. No case of high-grade (G3) disease was found in the 6 G1 biopsies (100%). Of 32 G2 biopsies, 9 were upgraded to G3. Cytology was available for 8 of the 9 and 5 (63%) were positive. For patients with G2 biopsies, combining cytology and biopsy grade improved the sensitivity and specificity of high-grade tumor detection from 43% to 55% and 23% to 85%, respectively. CONCLUSIONS: The results of this study have shown that biopsy grade reflects the pathologic stage and grade. Combining exfoliated cell cytology improved the predictive power of biopsy G2 disease for high-risk specimen grade. Exfoliated cell cytology in combination with biopsy grade is recommended as part of the evaluation of upper tract transitional cell carcinoma selected for endoscopic management.

Treatment of carcinoma in situ with intravesical bacillus Calmette-Guerin without maintenance.

PURPOSE: Data concerning the relative efficacy of intravesical bacillus Calmette-Guerin (BCG) on subgroups of carcinoma in situ of the bladder are limited. We report the outcome of primary carcinoma in situ and carcinoma in situ associated with Ta or T1 transitional cell carcinoma of the bladder treated with BCG. MATERIALS AND METHODS: Between 1987 and 1997, 135 patients (median age 70 years) with biopsy proven bladder carcinoma in situ underwent a standard course of 6 BCG instillations. Patients were divided into group 1-23 patients with primary carcinoma in situ, group 2-37 with carcinoma in situ associated with Ta transitional cell carcinoma and group 3-75 with carcinoma in situ associated with T1 transitional cell carcinoma. RESULTS: Median followup was 41 months. For groups 1 to 3, complete response rates at 3 months were 74% (17 of 23 cases), 70% (26 of 37) and 75% (56 of 75), respectively. The overall progression rates at 5 years were 20% (3 of 15 cases), 18% (4 of 22) and 49% (25 of 51). Cancer specific survival rates were 83% (10 of 12 patients), 86% (12 of 14) and 59% (17 of 29), and the numbers of patients alive with the bladder intact were 60% (9 of 15), 58% (11 of 19) and 30% (12 of 40). Patients in group 3 treated with BCG had progression significantly earlier than those in groups 1 and 2 (log-rank test p = 0.013). A complete response to BCG in group 3 patients significantly delayed time to progression (Cox regression p = 0.001) but did not reduce death from transitional cell carcinoma. Indeed, only 38% (8 of 21) of complete responders were alive with the bladder intact at 5 years. CONCLUSIONS: A single course of BCG is remarkably effective for primary carcinoma in situ and carcinoma in situ associated with Ta transitional cell carcinoma but is suboptimal in patients with carcinoma in situ associated with T1 transitional cell carcinoma. Better outcomes in each of the 3 groups may have occurred with maintenance BCG.

Unanswered questions in screening for prostate cancer.

Prostate cancer fulfils some of the conditions required of a disease that might be managed by population screening. In a cohort of 50- to 60-year-old men, carrying out a rectal examination and prostate specific antigen (PSA) test will detect clinically suspicious areas within the prostate in approximately 5%, and approximately 10% will have a raised PSA. We are however unsure which of the prostate cancers that are known to be present in approximately 30-40% of men aged over 60 years will be detected. Eventually after such screening, around 4% of men with an otherwise normal prostate will be found to have prostate cancers. The use of rectal examination may increase the number of tumours found, but will reduce compliance. The use of free/total PSA ratios will reduce the number of unnecessary biopsies at the expense of missing some tumours. Of more concern, we remain uncertain how effective aggressive local treatment is in altering the natural history of the disease. The risk of a 50-year-old man with a 25 year life expectancy of having microscopic cancer is 42%, of having clinically evident cancer is 9.5%, and of dying of prostate cancer 2.9%. Only a small proportion of cancers known to be present become clinically evident: more men die with prostate cancer than of it. Screening will identify some men with cancer who will not benefit from treatment. It is unclear whether screening would be followed by a reduction in morbidity and mortality. Recent data suggest a screening effect has been observed in the USA with: an increase in incidence, a decrease in men with distant metastases. The small decrease in mortality recently observed (many times smaller than the increase in incidence) may be confounded by inappropriate 'attribution' of cause of death, the detection of men with better prognosis distant metastatic disease responsive to hormonal ablation and changes in social factors such as diet. Future changes may incorporate molecular markers that might aid identification of men best treated aggressively because of a risk of progression. Tests to identify genetic pre-disposition may also allow targeted screening. New treatments and early chemoprevention or dietary strategies will again shift the ground on which these arguments are being rehearsed. The most urgent evidence required concerns the effectiveness of treatment strategies.

Epididymectomy is an effective treatment for scrotal pain after vasectomy.

OBJECTIVE: To investigate the efficacy of epididymectomy in patients with significant scrotal pain after vasectomy. PATIENT AND METHODS: Sixteen patients were identified retrospectively to have undergone epididymectomy for pain after vasectomy; 19 epididymectomies were performed (three bilateral and 13 unilateral). Details from the preoperative investigations, histological examination and follow-up of symptoms were analysed and correlated. Outcomes were initially assessed at the routine outpatient clinic review 3 months after surgery and the long-term outcomes were assessed by a telephone interview 3-8 years after epididymectomy (mean 5.5 years). RESULTS: Of the 16 patients, 14 had excellent initial symptomatic benefit from epididymectomy. At 3-8 years afterward, nine of 10 patients interviewed had a sustained improvement of their scrotal pain. The following were indicators of a poor outcome: atypical symptoms including testicular or groin pain; erectile dysfunction and normal appearance of the epididymis on ultrasonography. Patients with bilateral scrotal pain can have a good outcome after epididymectomy. CONCLUSION: Epididymectomy in well-selected patients is a reliable and effective treatment for pain after vasectomy.

A prospective analysis of 1,930 patients with hematuria to evaluate current diagnostic practice.

PURPOSE: The commonly accepted diagnostic algorithm for hematuria includes excretory urography (IVP) and cystoscopy. Some have suggested that ultrasound of the upper urinary tract is adequate and that cystoscopy is not necessary in younger patients with microscopic hematuria. We ascertain whether a less intensive algorithm could be adopted while retaining diagnostic efficacy. MATERIALS AND METHODS: A total of 1,930 patients were enrolled prospectively in the study at a hematuria clinic between October 1994 and March 1997. Evaluation consisted of basic demographics, history and examination, routine blood tests, urinalysis and cytology. All patients underwent plain abdominal radiography, renal ultrasound, IVP and flexible cystoscopy. RESULTS: A total of 1,194 males and 736 females with a mean age of 58 years (range 17 to 96) were included in the study. Overall, 61% of patients had no basis found for hematuria, 12% had bladder cancer, 13% had urinary tract infection and 2% had stones. Kidney and upper tract tumors were noted in 14 patients (0.7%), including 4 who presented with microscopic hematuria. If only ultrasound or IVP had been performed 4 of these cases would have been missed. Of 982 patients presenting with microscopic hematuria 51 had cancer. Bladder cancer was found in 7 patients younger than 40 years. CONCLUSIONS: Our findings suggest that cystoscopy cannot be safely avoided even in younger patients with microscopic hematuria. Only a combination of ultrasound and IVP detected all upper tract tumors.

Nitric oxide and cyclic GMP formation following relaxant nerve stimulation in isolated human corpus cavernosum.

OBJECTIVE: To investigate further the role of the nitric oxide (NO)-cyclic GMP pathway as the mediator of relaxant neurotransmission in human corpus cavernosum and to establish whether impaired activity of this pathway contributes to the pathophysiology of impotence. PATIENTS AND METHODS: Samples of cavernosal tissue were obtained from 59 men undergoing penile operations. The controls comprised four men with penile carcinoma and 17 with Peyronie's disease. Of the impotent men, 35 had clinical evidence of penile vascular disease on pre-operative investigation, whilst three had non-vascular impotence. Each biopsy was divided into two strips which were then suspended under tension in organ bath chambers. The relaxant innervation of one strip of each pair was stimulated electrically whilst the other strip was left unstimulated. The formation of NO and cyclic GMP was calculated by comparing their respective tissue content in the stimulated and unstimulated strips. RESULTS: Overall, stimulation of the relaxant innervation produced significant increases in the tissue content of both NO and cyclic GMP. Incubation with an inhibitor of NO biosynthesis abolished the mechanical relaxant response and the formation of both NO and cyclic GMP. The magnitude of relaxant response and the formation of NO was diminished in tissue from men with vascular impotence compared to controls. The increase in cyclic GMP content was similar in both these groups. Relaxant response, NO formation and cyclic GMP formation in tissue from men with non-vascular impotence was similar to controls. CONCLUSIONS: This study provides further evidence that the NO-cyclic GMP pathway acts as the mediator of nerve-evoked smooth muscle relaxation in human corpus cavernosum. Diminished NO formation following relaxant nerve stimulation may account for impaired relaxant responses found in tissue from men with vascular impotence and may contribute to the cause of their erectile dysfunction.

The use of duplex ultrasound in the assessment of arterial supply to the penis in vasculogenic impotence.

Impotence may be caused by arterial disease affecting the vessels supplying the corpora cavernosa. Color duplex ultrasound was used to measure the peak systolic velocity and systolic rise time in the deep penile arteries in 22 impotent men following papaverine stimulation. The results were compared with the findings of selective internal pudendal pharmaco-arteriography. A further comparison was made using color duplex ultrasound with 37 impotent men who all responded well to papaverine. A systolic rise time of 110 msec. or more was found to be the best discriminant of disease in the arteries supplying the corpora giving a positive predictive value of 0.92. A long systolic rise time in a papaverine responder may indicate that the arterial supply is borderline or that the arterial flow is maximal and that the problem lies on the sinusoidal-venous side. It appears that in the absence of a pathological condition there is a large surplus arterial supply.

Corpus cavernosal relaxation in impotent men.

OBJECTIVE: To investigate smooth muscle responsiveness in isolated preparations of corpus cavernosum from men with vasculogenic impotence. PATIENTS AND METHODS: Biopsies of corpus cavernosum were obtained from 63 men undergoing penile surgery. These included a control group of eight men (mean age 59 years, range 38-82) undergoing penile amputation for carcinoma, 47 men with vasculogenic impotence (mean age 58, range 36-72) who were further sub-divided into arterial (n = 9), venous (n = 24) or mixed arterial/venous (n = 14) impotence according to the results of pre-operative haemodynamic investigation, and eight men with non-vasculogenic impotence (mean age 49 years, range 34-66). Smooth muscle contractile responses to alpha-adrenoceptor activation and relaxant responses to stimulation of intrinsic nerves and exposure to papaverine and sodium nitroprusside were recorded in tissue strips prepared from the biopsies. Morphology was assessed histologically using haematoxylin and eosin staining of tissue sections together with immunocytochemical labelling of intrinsic nerves. RESULTS: Nerve-evoked relaxation was markedly impaired in tissue from men with venous or mixed arterial/venous impotence. A lesser degree of impairment was found in tissue from men with arterial impotence alone. Tissue from men with all types of vasculogenic impotence also showed a decreased contractile response to alpha-adrenoceptor stimulation. The magnitude of relaxant responses to papaverine and sodium nitroprusside in the vasculogenic group was similar to that of the control. There were no differences in smooth muscle content or nerve density between the vasculogenic group and the control. In the non-vasculogenic group responses to relaxant nerve stimulation, alpha-adrenoceptor activation and relaxant drugs were similar to those of the control. Nerve density in this group was similar to the control but smooth muscle content was reduced. CONCLUSIONS: The results of this study demonstrate a functional impairment of smooth muscle contractility and neurogenic relaxation in corpus cavernosum from impotent men with abnormal penile haemodynamics. Altered smooth muscle responsiveness is likely to be a factor in the aetiology of impotence in such men and may contribute to the relatively poor results of vascular surgery for impotence.

The clinical application of dorsal penile nerve cerebral-evoked response recording in the investigation of impotence.

OBJECTIVE: To determine whether recording of penile cerebral-evoked response (CER) is useful in the assessment of men with impotence. PATIENTS AND METHODS: A total of 280 impotent men underwent CER recording as part of an assessment for a complaint of impotence. They were categorized from findings in the history and examination as having non-neurogenic impotence (n = 106), impotence related to existing neurological disturbance (n = 67), type I diabetes (n = 49) or type II diabetes (n = 58). Increased period of latency or absence of first positive peak (P1) on CER were used as the criteria for an abnormal response with reference to an age-matched control group of potent men (n = 34). RESULTS: Overall, impotent men with diabetes or a history of neurological disturbance had significantly longer P1 latencies and lower response amplitudes compared with the control group. In contrast the CER recorded from men with non-neurogenic impotence was similar to the control group. Individual results showed an increased period of latency or absence of P1 in 100 (36%) impotent men, 72 (72%) of whom were diabetic or had a history of neurological dysfunction. CER abnormalities were associated with neurological signs on physical or cystometrographic examination in 40 (40%) individuals. CONCLUSION: Although technically satisfactory, the clinical usefulness of CER recording is limited by the poor discriminatory value of response latencies. Most abnormal results could be predicted by the presence of diabetes or pre-existing neurological dysfunction, or by evidence of neurological deficit on physical examination. The test is not therefore suitable for routine clinical assessment of impotence but may be worthwhile if objective evidence of penile sensory dysfunction is required.

Evidence against vasoactive intestinal polypeptide as the relaxant neurotransmitter in human cavernosal smooth muscle.

1. The putative role of vasoactive intestinal polypeptide (VIP) as the relaxant neurotransmitter in human cavernosal smooth muscle has been studied in isolated tissue preparations. 2. Consistent neurogenic relaxations were evoked by electrical field stimulation (EFS; 2-64 pulses/train, 0.8 ms pulse duration, 10 Hz). VIP (0.1-3 microM) relaxed cavernosal smooth muscle in a dose-dependent fashion. Relaxant responses to both EFS and VIP were reduced in tissue from impotent men. 3. Neurogenic relaxant responses were not diminished in the presence of the VIP-inactivating peptidase, alpha-chymotrypsin (alpha-CT, 2 units ml-1). In contrast VIP-induced relaxations were completely abolished. 4. Inhibition of nitric oxide synthase by NG-nitro-L-arginine (30 microM), and of guanylate cyclase by methylene blue (50 microM) caused highly significant reductions of neurogenic relaxant responses whereas VIP-evoked relaxations were unaffected. 5. It is concluded that VIP-evoked relaxations are not mediated by the NO-guanosine 3':5'-cyclic monophosphate (cyclic GMP) pathway and that VIP release is not essential for neurogenic relaxation of human cavernosal smooth muscle. VIP does not therefore act as the major relaxant neurotransmitter in this tissue.

The effect of inhibitors of nitric oxide biosynthesis and cyclic GMP formation on nerve-evoked relaxation of human cavernosal smooth muscle.

1. The inhibitory transmission in isolated preparations of cavernosal smooth muscle from human penis has been studied. 2. Electrical field stimulation (EFS; 2-64 pulses/train, 0.8 ms pulse duration, 10 Hz) evoked relaxation of preparations treated with guanethidine (50 microM). The EFS-evoked relaxations were atropine-resistant and tetrodotoxin-sensitive indicating their origin to be non-adrenergic, non-cholinergic (NANC) nerve stimulation. 3. EFS-evoked relaxation was attenuated dose-dependently by the nitric oxide (NO)-synthase inhibitor, L-NG-nitro arginine (L-NOARG; 0.3-100 microM) but not by D-NG-nitro arginine. The inhibitory effect of L-NOARG on transmission was antagonized by L-arginine (100 microM), a NO precursor, but not by D-arginine. 4. Incubation with methylene blue (10-50 microM), a known inhibitor of guanylate cyclase activation by NO, caused a concentration-related inhibition of EFS-evoked relaxation. 5. It is concluded that NANC nerve-evoked relaxation of human cavernosal smooth muscle is mediated by NO or a NO-like substance.

The role of colour duplex ultrasonography in the diagnosis of vasculogenic impotence.

Colour duplex ultrasonography was used to obtain peak systolic velocity (PSV) readings from cavernosal arteries at rest and during papaverine-induced tumescence. Results from 31 men with vasculogenic impotence were compared with those from 17 men with non-vasculogenic impotence and a control group of 6 potent men. In the flaccid state no significant differences in PSV readings were found between the vasculogenic and control groups. Following the injection of papaverine, men from the vasculogenic group without venous leakage were alone in having significantly lower PSV readings compared with the potent controls. All 23 men with normal penile haemodynamics had a mean PSV greater than or equal to 20 cm/s during tumescence. This was also the case for 19 (61%) of the vasculogenic group, including 9 (69%) of the 13 patients with venous leakage. The remaining 12 men in the vasculogenic group (39%) had a mean PSV less than 20 cm/s, this being diagnostic of an inadequate arterial inflow. Colour duplex ultrasonography can identify patients who have marked arterial insufficiency as the major cause of their impotence and hence allows more rational selection for angiography and revascularisation. Lesser degrees of arterial deficit are difficult to characterise using mean PSV readings alone.

Outcome of elective prostatectomy.

OBJECTIVES: To determine the symptomatic and urodynamic outcome of elective prostatectomy and to establish whether the outcome is influenced or can be predicted by preoperative urodynamic measurements. DESIGN: Prospective non-randomised study with follow up at a mean of 11 months after operation. Most men were assessed jointly by a urologist and a general practitioner. SETTING: Department of urology in a teaching hospital serving a large district population. PATIENTS: 253 Men listed for elective prostatectomy because of symptoms and low urinary flow rates (less than 15 ml/s) and excluding those already on a waiting list or with acute urinary retention, clinically apparent prostatic cancer, and neurological or cerebrovascular disease; 217 (86%) were followed up. INTERVENTION: Elective prostatectomy. MAIN OUTCOME MEASURE: Classification on the basis of relief of symptoms assessed by patients and urologist and general practitioner and of symptom scores obtained by questionnaire. RESULTS: Of the 217 men followed up, 171 (79%) had a satisfactory subjective review and 155 (72%) had a satisfactory review and also low symptom scores. An unsatisfactory outcome was associated with preoperative symptoms of urge incontinence, small prostatic size and resected weight, low voiding pressures, and low urethral resistance. Preoperative maximum urinary flow rates did not predict outcome. Men with poor outcome could be classified into two groups: those with irritative symptoms who were more likely before operation to have had urge incontinence and detrusor instability and men with symptoms of poor urinary flow who were more likely before operation to have had a small prostate, low voiding pressures, and low urethral resistance. In patients in the second group flow rates or voiding pressures improved little after operation. Men with stable detrusors and either low urethral resistance or low voiding pressures were less likely to do well after prostatectomy, but despite these associations preoperative urodynamic measurements were unable to predict outcome accurately. CONCLUSIONS: Prostatectomy was satisfactory in relieving symptoms and improving urodynamic measurements in most men, but even in those with classic symptoms and low urinary flow rates a substantial minority experienced little improvement afterwards and urodynamic measurements did not accurately predict outcome in individual patients.

Deferred treatment for prostate cancer.

The clinical outcome of 278 prostate cancer patients managed by a deferred treatment policy was analysed retrospectively. Following TURP or biopsy, all patients were asymptomatic and deemed suitable for management by a deferred treatment policy, i.e. hormone therapy or other forms of treatment were only initiated if and when symptomatic progression occurred. The overall 5-year survival rate was 30%; 18% of patients died from other causes without needing treatment for their prostate cancer; 11% were alive and untreated after 5 years' follow-up; 17% died from prostate cancer without further treatment. Poor tumour grade, anaemia, metastatic disease, a short history, presentation with retention, and a raised serum creatinine at presentation were associated with a poor prognosis.

Reproducibility of measurement of prostatic volume by ultrasound. Comparison of transrectal and transabdominal methods.

88 men undergoing elective prostatectomy were investigated by transrectal and transabdominal ultrasound. A repeat examination was performed by a second observer in 28 patients. The aims were to determine the correlation between transrectal and transabdominal ultrasonic estimation of prostatic volume and the degree of observer error. Transabdominal estimation of prostatic volume correlated well with the transrectal method (p less than 0.001) and good agreement between the two observers was found with both methods (p less than 0.001). In the individual patient, however, a wide variation in prostatic volume was found between the two observers and the two methods.