Chromosomal basis of adenocarcinoma of the prostate.

Prostate cancer is the most frequent malignancy and the second leading cause of cancer deaths among males in the Western world. The clinical course of the disease is highly complex, and genetic factors underlying tumorigenesis are poorly understood. The challenge that lies ahead is to identify the important gene(s) that causes adenocarcinoma of the prostate. Chromosomal findings by cytogenetic and molecular methods, including Southern blotting, microsatellite analysis, fluorescence in situ hybridization, and comparative genomic hybridization, revealed a high frequency of chromosomal aberrations of heterogeneous nature, including: -1, +1, -1q, +4, -6q, -7, +7, -8, -8p, -8q, +i(8q), -9, -9p, -10, +10, +11, -12, -13q, -16, -16q, +16, -17, +17, +17q, -18, +18, -18q, +19p, +20q, +X, -Xq, -Y, and +Y. Specific chromosomal regions of alterations were 1q24-25, 2cen-q31, 5cen-q23.3, 6q14-23.2, 7q22-q31, 8p12-21, 8p22, 8q24-qter, 10q22.1, 10q23-25, 11p11.2, 16q24, 17p13.1, 18q12.2, and Xq11-12. Recently, a predisposing gene for early onset has been localized on 1q42.2-43. The losses of heterozygosity at specific chromosomal loci from chromosomes 5q, 6q, 7q, 8p, 8q, 10q, 13q, 16q, 17p, 17q, and 18q are generally correlated with poor prognosis in advanced tumor stage. In addition, an abnormal function of known tumor suppressor genes from these regions have been observed in prostate cancer. Although, the amplification of the androgen receptor gene at Xq11-13 and HER-2/neu gene at 17q11.2-q12 are novel findings, no single gene has been implicated in harboring prostate cancer. Frequent inactivation of PTEN/MMAC1 tumor suppressor gene at 10q23, MXI-1 at 10q25, KAI-1 at 11p11.2, Rb at 13q14.2, and p53 at 17p13.1 and deregulation of c-myc oncogene at 8q24 have recently been the subject of intense scrutiny and debate.

"Skin-CNS-bladder" reflex pathway for micturition after spinal cord injury and its underlying mechanisms.

PURPOSE: A "skin-CNS-bladder" reflex pathway for inducing micturition after spinal cord injury has been established in cat. This reflex pathway which is basically a somatic reflex arc with a modified efferent limb that passes somatic motor impulses to the bladder, has been designed to allow spinal cord injured patients to initiate voiding by scratching the skin. MATERIALS AND METHODS: The skin-CNS-bladder reflex was established in the cat by intradural microanastomosis of the left L7 ventral root (VR) to the S1 VR while leaving the L7 dorsal root (DR) intact to conduct cutaneous afferent signals that can trigger the new micturition reflex arc. After allowing 11 weeks for axonal regeneration, urodynamic, pharmacological and electrophysiological studies were conducted in pentobarbital or chloralose anesthetized animals. RESULTS: A detrusor contraction was initiated at short latency by scratching the skin or by percutaneous electrical stimulation in the L7 dermatome. Maximal bladder pressures during this stimulation were similar to those activated by bladder distension in control animals. Electrophysiological recording revealed that single stimuli (0.3 to 3 mA, 0.02 to 0.2 msec duration) to the left L7 spinal nerve in which the efferent axons had degenerated evoked action potentials (0.5 to 1 mV) in the left S1 spinal nerve distal to the anastomosis. In addition, increases in bladder pressure were elicited by trains of the stimuli (5 to 20 Hz, 5 seconds) applied to the L7 spinal nerve. Urodynamic studies including external sphincter EMG recording demonstrated that the new reflex pathway could initiate voiding without detrusor-external urethral sphincter dyssynergia. Atropine (0.05 mg./kg., i.v.) or trimethaphan (5 mg./kg., i.v.), a ganglionic blocking agent, depressed the bladder contractions elicited by skin stimulation. The skin-CNS-bladder reflex could also be elicited after transecting the spinal cord at the L2-L3 or L7-S1 levels. CONCLUSION: The cross-wired somato-autonomic bladder reflex is effective in initiating bladder contractions and coordinated voiding in cats with an intact neuraxis and can also induce bladder contractions after acute transection of the lumbar spinal cord. The new pathway is mediated by cholinergic transmission involving both nicotinic and muscarinic receptors. It is concluded that somatic motor axons can innervate bladder parasympathetic ganglion cells and thereby transfer somatic reflex activity to the bladder smooth muscle.

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.

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.

A possible new reflex pathway for micturition after spinal cord injury.

In order to restore bladder function after spinal cord injury, a controllable new reflex pathway has been established in rats. It involves a somatic reflex arc with an artificially modified efferent branch which passes the somatic motor impulses to the bladder. This is achieved by intradural microanastomosis of the left L4 ventral root to L6 ventral root, while leaving the L4 dorsal root intact as a starter of micturition. The 'skin-CNS-bladder' reflex pathway is designed to initiate voiding by scratching the skin. After axonal regeneration, 15 of the 24 rats with the new pathway underwent electrophysiological study. Single stimuli (0.3-3 mA, 0.02-0.2 ms duration) to the left L4 nerve resulted in evoked potentials (0.5-1 mV) recorded from the left L6 nerve distal to the anastomosis. The bladder detrusor contraction was very quickly initiated by trains of the stimuli and bladder pressures increased rapidly to levels similar to controls. Neural tracing study with horseradish peroxidase (HRP) on six rats with the pathway demonstrated that the somatic motor axons regenerated successfully into the pelvic nerve, and the bladder was reinnervated by the L4 somatic motor neurons. The bladder contraction can also be initiated by electrostimulation of left sciatic nerve as well as scratching the L4 related skin. A new concept may be derived from the skin-CNS-bladder reflex pathway: the impulses delivered from the efferent neurons of a somatic reflex arc can be transferred to initiate responses of an autonomic effector.

Simultaneous presence of schistosomiasis and advanced cancer in prostate.

A forty-nine-year-old patient was found to have Schistosoma eggs inside his prostatic cancer. At the time of diagnosis, the patient already had spread of metastatic disease in lumbar spine. Review of the literature revealed this to be the first such case published in English literature. Despite advanced stage of disease (Stage D2), the patient responded well to immediate orchiectomy and regional irradiation. Two years after diagnosis was established, the patient was without clinical evidence of disease, when he suddenly died. The cause of death was not established because the family declined an autopsy.

Initial experience with therasonic lithotriptor.

Piezoelectric shock wave lithotripsy has been shown to offer a low-cost, safe, anesthesia-free yet effective means of disintegrating urinary calculi. The Therasonic lithotriptor combines proprietary piezoelectric shock wave technology for effective stone fragmentation with a multi-purpose urologic table and both fluoroscopic and ultrasound imaging for accurate stone localization and real-time treatment monitoring. From December 1, 1988 to November 15, 1989, 138 patients with 172 calculi were treated (94.2% were intrarenal, 5.8% were in ureter). All stones greater than or equal to 4 mm were considered suitable for treatment. Lithotripsy was performed under intravenous sedation except when ancillary procedures were necessary. For evaluation of device effectiveness, 94 patients were available with follow-up greater than or equal to thirty days. Successful fragmentation (stone free or residual debris less than or equal to 4 mm) was achieved in 97 percent of patients. The retreatment rate for stones 0.5-2.0 cm was 11 percent, and the overall retreatment rate was 21.2 percent regardless of stone size. Complications were minimal, transient, and resolved spontaneously.

Asynchronous erosion of inflatable penile prosthesis into small and large bowel.

Complications of a 3-piece inflatable penile prosthesis reservoir are rare, with rupture and fluid leakage being the most common. We recently encountered a patient in whom the reservoir migrated twice into the bowel. A review of the literature suggests that a previous major pelvic or abdominal operation might contribute to erosion of the reservoir into the adjacent viscera.

A retrospective analysis of the metabolic status of stone formers in the New York City metropolitan areas.

Eighty stone-forming patients were evaluated as outpatients for risk factors involved in stone formation. Analyses of the major stone risk parameters in the 24-hour collections indicated low volume (less than 2L) in about 79% of these patients. Forty percent of all patients were found to be hypocitraturic, 30% were hyperoxaluric, 18% were hypercalciuric, and 13% were hyperuricosuric. Sixty-one percent of the patients had a normal calcium load study; of these, four patients were uric acid stone formers. The remaining 39% of patients were classified as either absorptive hypercalciuric (16 patients), or fasting hypercalciuric with normal (12 patients) or elevated (3 patients) serum parathyroid hormone (PTH) levels. Of these 31 patients, 61% were not hypercalciuric on the basis of the 24-hour urine collections. The protocol provided a diagnosis in over 98% of patients. Low urinary volume was the only defect found in 5% of patients, while more than one risk factor was identified in 93%.

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.

Arteriovenous malformations of the bladder.

We report a rare case of a localized arteriovenous malformation of the bladder mimicking a bladder tumor and presenting with gross hematuria. The mass was successfully resected transurethrally.

Traumatic acute incarcerated scrotal hernia.

A 23-year-old male presented to the ER with left scrotal pain and swelling after being struck with a knee in the left inguinoscrotal area during a basketball game. Upon examination, an incarcerated scrotal hernia with necrotic segment of small bowel was found. Bowel was resected and direct reanastomosis performed. This appears to be the first such case in the English-language literature.

The erect penis--injury prone organ.

Erection converts the safe, flaccid penis into a vulnerable organ. During erection, the usually thick tunica albuginea becomes very thin and easily fracturable. Penile fracture is an under-reported urologic injury, with only approximately 100 cases reported in the world literature. We report on three cases, one with rupture of one corpus spongiosum and two with rupture of both corpora cavernosa associated with almost complete transection of the urethra. All three cases were treated surgically, with good outcome and no postoperative complications. The authors postulate that some cases of deviation of the penis are actually the result of some minor degree of penile fracture.

Triple therapy for adult Wilms tumor.

Adult Wilms tumor is still considered a rarity. Approximately 170 adult Wilms tumors have been reported. The final diagnosis is usually established with surgery. There is no specific radiologic diagnosis of adult Wilms tumor. We report on a case of Wilms tumor in a twenty-two-year-old black man. The tumor was removed with radical nephrectomy and classified as Stage II. Radiation of the renal fossa (4,000 rad) and chemotherapy with actinomycin D and vincristine were administered after surgery. Six years after surgery the patient is disease free. A review of published cases of adult Wilms tumor is presented, and a plea is made for triple therapy.

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.

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.

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.