Single photon emission computerized tomography with capromab pendetide plus computerized tomography image set co-registration independently predicts biochemical failure.

PURPOSE: We evaluate the usefulness of pretreatment (111)Indium capromab pendetide (ProstaScint) planar imaging (immunoscintigraphy) plus single photon emission tomography co-registration with computerized tomography scans to detect occult metastatic disease and predict for biochemical failure, in a cohort of patients with a clinical diagnosis of localized adenocarcinoma of the prostate referred for primary radiotherapy. MATERIALS AND METHODS: Patients were followed after radiotherapy for evidence of biochemical failure using 2 criteria of prostate specific antigen clinical nadir +2 ng/ml and American Society for Therapeutic Radiology and Oncology Consensus definitions. Median followup was 58.8 months (mean 64.8). Clinical risk factors defined 3 risk groups of high (51), intermediate (72) and low (116). RESULTS: Overall biochemical failure was 18.3% vs 11.8% by the 2-BFC at 8-year actuarial analysis with 58.8 months median followup. By the CN +2 definition the control date for the cohort is 34.8 months. Pretreatment SPECT/CT suggested prostate cancer metastasis (22), seminal vesicle extension (20) and organ confined disease (197). Biochemical failure in patients having extra-periprostatic metastatic prostate cancer, seminal vesicle extension and organ confined disease uptake on SPECT/CT was 43.2%, 16.0% vs 14.7% (p = 0.0006); and 33.3%, 15.0% vs 8.7% (p = 0.0017) by the 2-BFC, respectively. Cox multiple regression analysis demonstrated that a finding of extra-periprostatic metastatic prostate on SPECT/CT significantly predicted a 4.2-fold greater risk (p = 0.0012) and a 4.5-fold greater risk (p = 0.0011) of failure by the 2-BFC than organ confined disease adjusting for treatment and risk group. CONCLUSIONS: Unconfirmed findings of extra-periprostatic metastatic prostate cancer on SPECT/CT immunoscintigraphy independently and significantly predicted an increased risk of biochemical failure in patients presenting for radiotherapy with a clinical diagnosis of localized prostate cancer.

Xenografts of primary human prostatic carcinoma.

BACKGROUND: Prostatic carcinoma is both the most common invasive cancer and the second most common cause of cancer deaths in men in the United States. Before 1991, attempts to propagate prostatic carcinoma from primary tumors for periods longer than 3 months were unsuccessful in vivo and in vitro with rare exceptions. In 1991, we reported establishment of slowly growing tumors for six of 10 human primary prostatic carcinomas approximately 2-6 months after transplantation. However, none of the tumors were larger than 5 mm or serially transplantable. PURPOSE: Our purpose in this study was to determine whether human primary prostatic carcinoma could be grown as serially transplantable xenografts. METHODS: Cells from primary prostatic carcinomas obtained from transurethral prostatic resections or total prostatectomies in 20 patients were injected subcutaneously into male nude mice on the day of surgery. Sustained-release testosterone pellets were placed subcutaneously in the mice 2-24 days before transplantation of tumors and at intervals of 10-12 weeks. Serial transplantations in subsequent generations of mice were carried out by similar methods. Chromosome analysis was performed on six tumors. RESULTS: Six of 20 primary prostatic carcinomas have grown sufficiently to permit serial transplantation into second mice; four have been documented histopathologically in the second mouse and serially transplanted into three or more successive mice. When a single primary tumor was injected into several mice by the same procedure, tumors failed to grow in some recipients but became serially transplantable in others. Growth of these tumors is slow and irregular, with frequent regressions. Short-term cultures of 10 tumors, eight of which were injected into mice in parallel, were initiated on the day of surgery; CWR31, which was successfully transplanted serially, exhibited only aberrant metaphases and showed clonal, chromosomal changes in culture. Including CWR31, three of the six tumors for which chromosomal analysis was successful contained clonal aberrations. Preliminary studies of SCID (severe combined immunodeficient) mice suggest that they are not superior to nude mice for establishment of serially transplantable prostatic carcinoma xenografts. CONCLUSIONS: A proportion of human primary prostatic carcinomas can be grown as xenografts. Four new serially transplantable xenografts (CWR21, CWR31, CWR91, and CWR22) are currently propagated in our laboratory, a resource that was not previously available. IMPLICATIONS: Our experience suggests that the most important factor in serial transplantation is the collaboration of urologists and pathologists in expediting placement of the tumor in cold saline, examination of the frozen section, and transplantation.

CWR22: androgen-dependent xenograft model derived from a primary human prostatic carcinoma.

The long-term propagation of primary human prostate cancer (PCA) in vivo or in vitro has been rare. Most such PCAs are phenotypically different from most PCAs in humans; i.e., they make little prostate specific antigen and respond little, if at all, to androgen deprivation. A serially transplantable, primary human PCA, designated CWR22, exhibits a clonal cytogenetic aberration, causes high elevations of prostate specific antigen in the peripheral blood of nude mice, and is unusually responsive to androgen deprivation as compared with other xenografts. Studies of mRNA from CWR22 have demonstrated the expression of prostate specific antigen and the epidermal growth factor receptor family including erbB1/epidermal growth factor receptor, erbB2/neu, and erbB3, but not erbB4. A ligand for these receptors, the neu differentiation factor, is also expressed.

Alternative method of nerve-sparing when performing radical retropubic prostatectomy.

An alternative method of preserving the pelvic parasympathetic nerve plexus and potency when performing a radical retropubic prostatectomy is described. The prostate is removed in an antegrade manner as opposed to the classic retrograde approach with a current potency rate of 60 percent. The advantages of this technique are ease of defining the lateral vascular pedicles and late transection of the dorsal vein complex to minimize bleeding early in the procedure.

Palliative nephrostomy for relief of ureteral obstruction secondary to malignancy.

A mean survival of 7.6 months in 20 patients undergoing nephrostomy for relief of ureteral obstruction from advanced pelvic malignancy was not as dismal as previous reports have indicated. Patients with bilateral ureteral obstruction from direct extension of pelvic malignancy survived considerably longer and appear to be the best candidates for nephrostomy. The physician must be cautious in advising the procedure to patients with bilateral ureteral obstruction from disseminated disease originating outside the pelvis since mean survival in this group (3 patients) was less than one month. Nephrostomies were associated with a significant incidence of perinephric abscess (15 per cent) emphasizing the technical aspect of accurate placement to avoid leakage of potentially infected urine.

Intraurethral alprostadil for treatment of erectile dysfunction in patients with spinal cord injury.

OBJECTIVES: To assess the efficacy of intraurethral prostaglandin E1 (alprostadil, MUSE) in treating erectile dysfunction in patients with spinal cord injury (SCI). METHODS: Intraurethral alprostadil was tested in 15 patients with SCI to evaluate its effectiveness in treating SCI-associated erectile dysfunction. All patients were at least 1 year after injury, and all had previously used intracavernosal injections successfully (Schramek's grade 5 erection). The intraurethral drug was administered in the office, in the presence of a physician, with monitoring of blood pressure. If effective, the patient was then able to use MUSE at home. The first 3 patients underwent gradual dose escalation starting with 125 microg, without the use of a constriction ring. Because of hypotension, the remaining 12 patients all used a penile constriction ring prior to intraurethral drug administration using 1000 microg. The quality of the erection was compared with that achieved with intracavernosal injections using Schramek's grading. RESULTS: The dose escalation (titration) in the first 3 patients demonstrated that the 1000-microg dose was the most effective in creating an erectile response. Transient hypotension was noted in these first 3 patients in whom the constricting band was not used. The highest dose of MUSE (1000 microg) was, therefore, used in the remaining 12 patients, with the constriction band. The quality of the erection varied and appeared to be less rigid in all patients (12 patients with grade 1 to 3; 3 patients with grade 4) than that noted with intracavernosal injection therapy (1 5 patients with grade 5). There was no incidence of priapism. The 3 patients with grade 4 erections tried the MUSE at home. All 3 patients were dissatisfied with the quality of the erection and did not continue to use the MUSE at home and returned to intracavernosal injection therapy. CONCLUSIONS: MUSE appears to be somewhat effective in creating erections; however, these were less rigid erections than those obtained with intracavernosal therapy and provided less overall satisfaction. It should always be used in the patient with SCI after placement of a constriction ring to prevent hypotension. Its ultimate use depends on the patient's level of satisfaction with the quality of the erection compared with intracavernosal injections.

Acquired infundibular stenosis.

Acquired infundibular stenosis is an unusual complication resulting in pancalyceal obstruction. We have cared for 6 patients with acquired infundibular stenosis not associated with tuberculosis. All patients had urinary diversion with ileal conduits for a minimum of eleven years and documented ileal-ureteral reflux and chronic urinary tract infections. The clinical, radiographic, and pathologic characteristics of this syndrome are described and therapeutic guidelines suggested.

Hepatotoxicity related to intracavernous pharmacotherapy with papaverine.

OBJECTIVES: To determine the incidence of hepatotoxicity related to self-administration of intracavernous papaverine or papaverine/phentolamine (bimix). METHODS: From October 1994 through June 1996, we retrospectively reviewed the medical records of 71 consecutive patients diagnosed with organic erectile dysfunction (ED) and receiving intracavernous injection therapy. Inclusion criteria were documentation of normal baseline liver function tests (LFTs), a minimum of 6 months of follow-up that included LFTs, at least one self-injection every 2 weeks, and no other prior or concurrent treatment for ED. Thirty evaluable patients satisfied the inclusion criteria and formed group 1. Mean age was 63 years (range 40 to 77), mean follow-up was 18 months (range 6 to 32), and mean number of injections per month was 5.7 (range 3 to 12). An age-matched population of 20 patients (mean age 69 years, range 46 to 90) without ED but with similar comorbid risk factors formed the control group (group 2). All patients in group 2 had routine long-term follow-up of LFTs (mean 52 months, range 10 to 1 14). RESULTS: Two patients (6.67%) from group 1 had elevated LFTs during treatment: one experienced a mild elevation in alanine aminotransferase and the other developed transient elevations of total bilirubin and aspartate aminotransferase 6 months after beginning therapy. Both patients reported a history of alcohol abuse. Both patients remained asymptomatic. Neither patient required discontinuation of therapy. One patient (5%) from group 2 developed an elevation of total bilirubin at a follow-up of 12 months. CONCLUSIONS: Routine monitoring of LFTs is probably unnecessary during intracavernous pharmacotherapy. Patients with a history of alcohol abuse or liver disease, however, should be followed up more closely when papaverine is selected for intracavernous injection. In these patients, LFTs should be obtained before initiating treatment and at 6-month intervals.

Twelve-month comparison of two treatments for erectile dysfunction: self-injection versus external vacuum devices.

This study directly compared two nonsurgical treatments for erectile dysfunction, self-injection of papaverine/phentolamine and external vacuum devices, in terms of usage rates, effectiveness, side effects, dropout rates, and impact on patient sexual and psychologic functioning. Both alternatives were regularly, successfully, and safely used by patients, though dropout rates were higher for self-injection. Both produced erections of improved quality, and effected sustained improvements in frequency of intercourse, orgasm, and sexual satisfaction. Spontaneous erections also improved with both treatments. General psychiatric symptomatology was decreased, and anxiety was improved. There were no differences between the two treatments in sexual or psychologic impact. Relative contraindications and esthetic considerations are presented.

The urethral syndrome.

The urethral syndrome remains a diagnosis of exclusion. The obvious difficulty is the lack of overall significance of this problem: patients with urethral syndrome do not die of their disease. More serious causes of urinary frequency, dysuria, and suprapubic discomfort must be excluded. A combination of a careful history, physical examination, inspection of the urine, urine culture, urine cytology, and cystourethroscopy with biopsy will make the diagnosis. One's personal bias about the etiology will often direct the evaluation. Selective usage of suppressive antibiotics along with reassurance and careful follow-up will prove effective in treating these patients. With greater understanding of lower urinary tract infections and the neurologic innervation of the bladder and urethra, it would seem appropriate for us to continue to develop a better understanding of the urethral syndrome, its etiology, and a more effective treatment rationale. A systematic approach must be maintained in the evaluation of these patients so that an appropriate treatment can be devised.

Sexual dysfunction after spinal cord injury.

Treatment of sexual dysfunction is an integral part of the rehabilitation of the patient with spinal cord injury. The degree of sexual dysfunction varies with the level and completeness of injury. A multidisciplinary approach is necessary to evaluate and treat these patients. Intracorporeal injections of vasoactive medications or vacuum devices are effective means of restoring erections in selected patients with spinal cord injury. Penile prostheses are rarely indicated for this purpose.

Ileal and jejunal conduit urinary diversion.

The indications for urinary diversion have changed in recent years, and it is most often required in association with radical surgery for pelvic malignancies. Many patient with lower urinary tract dysfunction can be managed satisfactorily without diversion by use of intermittent catheterization, administration of specific pharmacologic agents, and, when necessary, implantation of artificial sphincters. For patients who require urinary diversion, the ureteroileal conduit remains the standard by which other methods should be judged. If satisfactory results are to be obtained, it is clear that meticulous attention to indications, operative technique, and careful follow-up are essential. As many of these patients have other disabilities, the management of the urinary tract must be integrated with other aspects of patient care. The introduction of the colonic conduit and recently the continent types of urinary diversion represent a search for the ideal method that has yet to be achieved.

Injection therapy for impotence.

Injection of vasoactive drugs is an effective form of treatment for selected patients with impotence from virtually all causes. The two most commonly employed drugs in the United States are either papaverine alone or various combinations of papaverine and phentolamine. Patients with organic and mixed impotence are best suited for injection treatment, but selected patients with psychogenic impotence also benefit from therapy. After the patient is selected for injection therapy, he undergoes a series of trial injections in the physician's office. The incidence of priapism will be minimized if the initially administered doses are low and the patient is titrated to an appropriate dose level. Uncontrolled trials have revealed that injection treatment produces a satisfactory erection in 65 to 100 per cent of patients for a follow-up period of as long as 2 years with minimal side effects, but the dropout rate is high. If priapism does occur, it almost always responds readily to treatment with aspiration, low doses of an alpha-adrenergic agent, or both. The other common side effects are bruising or ecchymosis and nodule formation at the injection site. This latter complication has not been noted to cause significant abnormal penile curavature necessitating cessation of the program.

Urologic function after experimental cauda equina compression. Cystometrograms versus cortical-evoked potentials.

Twenty female beagle dogs underwent an L6-7 laminectomy and six dogs each had 25, 50 or 75% constriction of the cauda equina and 2 control dogs had laminectomy only. Cystometrograms were performed pre- and post-operatively and three months after constriction. Cortical evoked potentials were monitored pre- and post-operatively and monthly for three months. After three months of constriction, the cauda equina of these dogs in each group was examined histologically and vascular circulation was examined by latex and India ink injection (Spalteholz technique). The control dogs had normal CMGs and CEPs. Twenty-five percent constriction caused no CMG changes and mild CEP changes. Fifty percent constriction caused no statistically significant CMG changes, major CEP changes and venous congestion of the nerve roots and dorsal root ganglia. Seventy-five percent constriction produced severe CMG changes with detrusor areflexia, increased bladder capacity and clinical incontinence. CEPs also had marked deterioration. Vascular analysis revealed severe arterial narrowing at the level of constriction and venous congestion of the nerve roots and dorsal root ganglia. Blockage of axoplasmic flow and nerve root atrophy was seen in all dogs with 75% constriction. Cortical evoked potentials were the most sensitive predictor of neural compression. CMGs were not sensitive until severe compression was achieved. Bladder dysfunction, i.e., detrusor areflexia, appears to occur with blockage of axoplasmic flow and early sensory changes occur with neurovenous congestion.

Review of sacral electrical stimulation in the management of the neurogenic bladder.

In patients with spinal cord injury above the conus medullaris, electrical stimulation of the sacral anterior nerve roots can produce micturition with low residual volumes of urine and reduced urinary tract infection. Vowing pressures appear to be maintained at safe levels by the use of an intermittent pattern of stimulation. The procedure is usually combined with division of the sacral posterior roots, which increases bladder capacity and continence; this also increases bladder compliance, which may be protective for the upper urinary tracts.The procedure has now been applied in about 900 patients with spinal cord injury, some of whom have been followed up for over 15 years. The nerves do not appear to be damaged by long-term stimulation and technical faults with the equipment are now uncommon.

Impotence: evaluation and treatment.

Impotence is a multifaceted problem. Complex neurologic pathways intermingle to control specific vascular changes in a tightly controlled hormonal milieu. Although great progress has been made in understanding the mechanism of erection, further studies are needed. Careful history and physical examination along with appropriate laboratory tests and noninvasive penile vascular studies are important in differentiating organic from psychogenic impotence. Understanding the etiology of impotence permits a more logical and effective treatment plan. The advent of the semirigid and inflatable penile prostheses has provided a simple and effective treatment for patients with organic impotence for whom there were no treatment options available in the past. The continued improvement in the design of the prostheses and the simplicity with which they can be implanted have revolutionized the treatment of impotence. With newer prosthetic devices being developed, the penile prosthesis will continue to improve the quality of life for impotent patients.

International standards to document remaining autonomic function after spinal cord injury.

STUDY DESIGN: Experts opinions consensus. OBJECTIVE: To develop a common strategy to document remaining autonomic neurologic function following spinal cord injury (SCI). BACKGROUND AND RATIONALE: The impact of a specific SCI on a person's neurologic function is generally described through use of the International Standards for the Neurological Classification of SCI. These standards document the remaining motor and sensory function that a person may have; however, they do not provide information about the status of a person's autonomic function. METHODS: Based on this deficiency, the American Spinal Injury Association (ASIA) and the International Spinal Cord Society (ISCoS) commissioned a group of international experts to develop a common strategy to document the remaining autonomic neurologic function. RESULTS: Four subgroups were commissioned: bladder, bowel, sexual function and general autonomic function. On-line communication was followed by numerous face to face meetings. The information was then presented in a summary format at a course on Measurement in Spinal Cord Injury, held on June 24, 2006. Subsequent to this it was revised online by the committee members, posted on the websites of both ASIA and ISCoS for comment and re-revised through webcasts. Topics include an overview of autonomic anatomy, classification of cardiovascular, respiratory, sudomotor and thermoregulatory function, bladder, bowel and sexual function. CONCLUSION: This document describes a new system to document the impact of SCI on autonomic function. Based upon current knowledge of the neuroanatomy of autonomic function this paper provides a framework with which to communicate the effects of specific spinal cord injuries on cardiovascular, broncho-pulmonary, sudomotor, bladder, bowel and sexual function.

The development of urologic complications in relationship to bladder pressure in spinal cord injured patients.

The medical records of 88 patients followed through our spinal cord injury clinic were reviewed to determine if elevated intravesical pressures result in more urologic complications than are seen with low pressure bladders. Fifty-two of the patients were noted to have a high bladder pressure (sustained detrusor pressure greater than 40 cm water) on cystogram while 36 had low pressures. All patients had routine urine cultures, urodynamics, ultrasonography, radioisotope renal scans, and excretory urograms. Bladder management was directed at maintaining a low bladder pressure and included one or more of the following: intermittent catheterization, anticholinergics, alpha blockers, transurethral sphincterotomy, or indwelling catheters. Average follow-up was 6 years. Mild degrees of hydronephrosis were noted in seven (14 percent) of the patients with a high pressure bladder and in one (3 percent) with a low pressure bladder. Pyelonephritis was noted in two (4 percent) with high bladder pressure and two (5 percent) with low bladder pressure. Preservation of renal function occurred as the result of patient compliance with bladder management and bladder pressure. Sustained high detrusor pressure, when not corrected, leads to upper tract deterioration which was reversed by aggressive lower tract management.

Trimethoprim-sulfamethoxazole prophylaxis against urinary tract infection in the chronic spinal cord injury patient.

Suppressive therapy with antibiotics has long been thought to decrease the number of complications from the neuropathic bladder in spinal cord injury patients, but it may also induce resistance to antibiotics which subsequently causes difficulties in treating symptomatic urinary tract infections. Forty-three chronic spinal cord injury patients were randomized to continue to receive daily trimethoprim-sulfamethoxazole (TMP-SMX) urinary tract prophylaxis versus discontinuing antibiotic prophylaxis. Patients were all at least 6 months after spinal cord injury. Patients were followed for a minimum of 3 months, with weekly catheter urine cultures. The difference in the colonization rate at onset and after 3 months (percent of cultures with asymptomatic bacteriuria) between the control and prophylaxis group was not statistically significant (P > 0.1). There was a significant decrease in the percentage of TMP-SMX resistant asymptomatic bacteriuria in the control group, 78.8%, compared to 94.1% in the suppressive group (P < 0.05). There was no significant difference in the number of symptomatic urinary tract infections following the withdrawal of suppressive therapy between the control group, 0.035/week, and the prophylaxis group, 0.043/week (P > 0.5). There was a larger percentage of TMP-SMX resistant symptomatic urinary tract infections in the treated group, 42.5% versus 37.5% in the control group, but the difference was not significant (P > 0.5). Irrespective of the method of bladder management, suppressive therapy with TMP-SMX did not reduce the incidence of symptomatic bacteriuria and did increase the percentage of cultures resistant to TMP-SMX in asymptomatic patients.