Genetics of bladder cancer.

Bladder cancer manifests many different forms, ranging from superficial to aggressive muscle invasion, which suggests that various genetic alterations are responsible. Several attempts have been made to establish correlations between specific genetic alterations and various grades of the disease. Numerous types of chromosomal abnormalities have been observed, involving [1p, 1q, 2q, 3p, 4p, 5q, i(5p), +7, +8, 8p, 9p, 9q, 10q23-25, 11p, 11q, +11, 13q, 14q, 17p, 18q, 21q, and Y]. In addition, p53 mutations and loss of heterozygosity on various chromosomes have recently begun to shed light on the molecular pathways of transitional cell carcinomas of the bladder. We have begun to focus on specific genomic sites (especially 9q), although the heterogeneity of the disease and the variable presentation suggests divergent progression pathways. When the genetic basis of bladder cancer is fully understood, new diagnostic and therapeutic strategies will be developed, which in turn may promote better clinical management by pathologists and urologists.

Loss of heterozygosity of the TP53 tumor suppressor gene and detection of point mutations by the non-isotopic RNAse cleavage assay in prostate cancer.

Mutation within the TP53 tumor suppressor gene is a frequent occurrence in human cancers, resulting in a poor prognosis, response to therapy, and overall survival time. Mutations have been primarily detected in advanced prostate cancer; however, the involvement of the gene through loss of heterozygosity (LOH) in primary prostate cancers has not been investigated due to lack of identifiable polymorphisms within this gene. Using the nonisotopic RNAse cleavage assay (NIRCA), we screened for point mutations and identified an ApaI restriction site polymorphism located in intron 7 within the TP53 gene. This polymorphism allowed us to detect LOH in informative samples in a population of patients that underwent prostate biopsies and a population that underwent radical prostatectomies. Within the combined study population, 31 of 80 patients (38.75%) were informative for the polymorphism. Loss of heterozygosity was detected in 10 of the 31 samples (32.3%). Point mutations were identified in two samples. The identification of LOH in these patients suggests that the TP53 tumor suppressor gene may play a more active role in prostate cancer than was previously believed.

Highly complex chromosomal aberrations in bone marrow of a patient with metastatic prostate neoplasm.

Prostate cancer is the single most common malignancy among men in North America. Nevertheless, cytogenetic evaluation of bone marrow in patients with metastatic prostate neoplasm has been rare and, to date, only five such patients have been reported. We report an additional case where chromosomal abnormalities of a bizarre nature were found in the bone marrow. Though cytogenetic findings in prostate cancer are heterogeneously complex, the chromosome regions involved include 1p, 1q, 7q, 8p, 10q, 12p, and 17q and are considered hot spots. What is the significance of these so-called hot spots in metastasis of prostatic cancer to the bone marrow? At present, no meaningful conclusion can be drawn, as data are limited, but accumulation of such cases may provide valuable information concerning the role of chromosomal abnormalities in patients--specifically with metastatic stage--and may help urologists during therapeutic decision making, particularly if a genetic marker for aggressiveness can be determined.

Acute urinary retention in young homosexuals.

Acute urinary retention secondary to and intercourse was found in 4 homosexuals. All four were treated initially with an indwelling Foley catheter and then with bethanechol and phenoxybenzamine (Dibenzyline). Normal micturition was restored in all 4 patients. Anal dilatation can produce reflex bladder inhibition resulting in acute retention.

Detrusor hyperreflexia inhibited by anal dilatation.

Urge incontinence in 6 patients was found to be due to detrusor hyperreflexia. A cystometrogram was repeated during calibrated anal dilatation and showed increased bladder capacity and decreased hyperreflexia in 4 patients and a normal curve in 2 patients. The mechanism of this response is discussed.

Malignant Sertoli cell tumor of testicle.

The eleventh case of malignant Sertoli cell tumor of the testicle is described. The tumor displayed malignant character with local invasion into the epididymis. Retroperitoneal lymph node dissection revealed a malignant deposit around the left renal artery.

Comparative evaluation of impotence with vibration and nocturnal monitoring.

Vibratory stimuli were used for diagnostic evaluation of 130 impotent patients. The stimuli were applied to the glans penis, and erectile response was measured and displayed on a recorder. The erectile response to vibration was compared with nocturnal penile tumescence (NPT) monitoring and to artificially produced full erection. At the present time vibratory stimuli do not represent an alternative diagnostic method to NPT. However, the two methods are complementary. Erectile activity during vibration was detected in 43 of 130 patients. For these 43 patients further evaluation with NPT monitoring would not be necessary. Because vibration evaluation is performed as an outpatient procedure, it can contribute to a significant cost reduction in the evaluation of impotent patients.

Acute electrical stimulation for urinary incontinence.

Acute or maximal electric stimulation of the pelvic floor muscles has been used in incontinent patients who are suitable candidates for electrical stimulation, but unwilling or unable to use the anal plug electrodes. Seventeen of 20 patients had relief or improvement of their incontinence. However 5 of these 17 patients had a relapse of symptoms on follow-up, requiring a repeat treatment with acute or maximal electrical stimulation.

Clinical application of Pavlov conditioning reflexes in treatment of urinary incontinence.

A new method of treatment of urinary incontinence is described. A tape recorder with two outlets generates musical stimuli. One outlet brings direct unconverted musical stimuli to the patient's ear, the other outlet conveys the musical stimuli to a converter where the musical pulses are converted into electrical stimuli which are then applied to the patient's anus. At first stimultaneous application of stimuli into the ear and anus is performed and anal pressure response recorded. After conditioning takes place, music is applied to the patient's ear, stimulation to the anus is disconnected, and only anal pressure response is recorded. The patients are conditioned enough to generate good and response to aural stimulation only.

"Timed voiding"--a useful tool in the treatment of urinary incontinence.

Female patients need more privacy for micturition and are, therefore, more prone to suppress the normal micturition reflex. Due to postponed micturition, their bladders are usually full and during stress conditions urinary incontinence does occur. In 20 patients who had functional stress incontinence, the urologic and urodynamic evaluation was performed. When no major structural deformities were found, the timed voiding was taught to the patients. In 79 per cent of patients the urinary incontinence was cured by timed voiding only. Some of the patients who had positive urinary cultures became sterile following the new voiding patterns. The possible neurophysiologic mechanisms of timed voiding are discussed.

Simultaneous occurrence of transitional cell carcinoma and urothelial adenocarcinoma associated with xanthogranulomatous pyelonephritis.

We report on a patient with xanthogranulomatous pyelonephritis, in situ transitional cell carcinoma, and focal prosoplasia revealing abrupt conversion of transitional epithelium to moderately well-differentiated adenocarcinoma. The etiology and pathogenesis of mucinous adenocarcinoma in the renal pelvis very likely involves the prosoplastic transition of pre-existing transitional carcinoma to adenocarcinoma. The urologist should be aware of the increased possibility of this tumor developing in a patient with longstanding infection, and frozen section should be performed more often because the gross structure of the tumor frequently appears normal. This permits the urologist to change his surgical strategy if frozen section is positive for tumor.

Rapid and slow-fill gas cystometry. Influence on bladder capacity and diagnosis of hyperreflexic bladder.

Rapid-fill gas cystometry has been criticized for giving a falsely low value of bladder volume and for inducing an "artefact", the hyperreflexic bladder. This study in 72 patients revealed that the average capacity with slow-fill air cystometry was less than with rapid fill. The diagnosis of hyperreflexic bladder was made more often with slow fill than with rapid fill in these 72 patients.

Urethral injury due to external trauma.

Fifty-six patients with urethral injuries comprised 35 involving the posterior urethra and 21 involving the anterior urethra. Immediate retrograde urethrography confirmed the clinical diagnosis made when blood was found at the external urinary meatus after external trauma. Traffic accidents caused most of the posterior urethral injuries and were associated with severe injuries to multiple systems and a significant mortality rate (34 per cent). Primary realignment of the urethral injury by a urethral catheter in all cases of urethral rupture (plus a suprapubic cystostomy in most of these cases) resulted in a stricture rate of 62 per cent on follow-up. However, only half of these strictures required surgical correction. The incidence of incontinence was 10 per cent and of impotence 38 per cent.

Psychosocial aspects of micturition.

The complex act of micturition is still insufficiently understood and a controversial neuromuscular phenomenon. In humans, the urinary bladder reflects the constant accommodation to physiologic, psychologic, and social aspects of micturition. This article deals with these additional dimensions of micturition of which the urologist should be aware.

Endoscopic removal of staghorn calculi in patient with high urinary diversion.

The treatment of recurrent renal calculi in patients after ureteroileal urinary diversion is difficult, especially when urinary stones are formed in the presence of urinary tract infection. In many cases, these patients already have undergone multiple renal operations and more surgery could pose difficult technical problems. We report on a patient with a high urinary diversion in whom bilateral staghorn renal calculi developed, and then were endoscopically removed. The conversion of ureteroileocutaneous diversion to a high pyeloileocutaneous diversion is recommended in selected cases as alternate treatment for patients with recurrent stone formation.

Cholinergic receptors in corpora cavernosa.

In a group of 13 patients who underwent penile surgery, a small amount of cavernosal tissue was removed and examined for content of cholinergic receptors. Three patients did not display any amount of cholinergic receptors. Values in the other 10 patients ranged from 34 to 136 femtomols. In another group of 61 impotent patients with some degree of preserved erectile capacity, cholinergic stimulation was administered to the patients and the response monitored. Preliminary data displayed improved erectile capacity in 41 per cent. Further studies are needed to identify impotent patients who might respond favorably to cholinergic stimulation.

Bladder inhibition with functional electrical stimulation.

Spastic or hyperreflex bladder dysfunction can cause frequency, urgency, and incontinence. Detrusor activity was inhibited by FES (functional electrical stimulation) applied to the anal sphincter causing decreased bladder spasticity and increased bladder capacity. FES is indicated for incontinence not only because of weakness of the pelvic floor but also because of hyperreflex bladder.

Testosterone receptors in corpora cavernosa of penis.

Despite existing information that most impotent patients have normal serum testosterone, testosterone is still used frequently in the treatment of impotence. In 11 patients who underwent penile implantation, we measured the presence of testosterone receptors in the corpora cavernosa. An average value of 1.82 fmol/mg of protein cytosol was found in this group of patients. This value is too low to obtain any significant improvement in erectile function following testosterone application. Testosterone hypogonadism will likely remain the only indication in which testosterone application might improve organically triggered impotence.

Necrotizing infection of scrotum.

Necrotizing infection of the scrotum (Fournier gangrene) rapidly spreads to adjacent skin with fever and toxemia and is life-threatening. Subcutaneous gas and a foul-smelling wet discharge from the skin are usually present. The infection is not cured with antibiotic therapy alone and requires immediate extensive debridement of all necrotic tissue. Repeated debridement each several days under general anesthesia is necessary until healthy granulation is present in the wound. Reconstruction with skin flaps or skin grafts shortens hospitalization and prevents the dense scar tissue and immobility of the tests that can occur with spontaneous epithelization.

Primary renal aspergillosis.

Primary renal aspergillosis has been reported only five times previously. We report the first case with primary renal aspergillosis where reconstructive and not extirpative surgery was used. Patients who have predisposing factors such as diabetes, malignancies, or immunosuppression represent the primary target for fungal infection. In these patients the clinical picture of nonspecific and fungal pyelonephritis are similar. Therefore fungal infections should be considered in the differential diagnosis of urinary tract infections.