Periprostatic local anesthesia eliminates pain of office-based transrectal prostate biopsy.

Up to 96% of patient who undergo prostate biopsy report pain. We performed periprostatic local anesthesia injection in an effort to improve patient acceptance of prostate biopsy. Sixty patients were randomized to receive either local injection of lidocaine in the periprostatic nerves or no anesthetic. Lidocaine was injected through a 7-inch spinal needle placed through a transrectal ultrasound biopsy guide. Ten-core biopsies were immediately performed. Following biopsy, all patients gave a Visual Analog Scale (VAS) assessment of their pain experienced during biopsy.A majority of patients reported Visual Analog Scale (VAS) scores in the moderate (28.6%) or severe (28.6%) ranges unless local anesthesia was given. Only one of 27 patients (3.7%) receiving local anesthetic reported moderate pain, and none reported severe pain. Mean VAS pain scores were 1.4 in the anesthetic group and 4.5 in the control group (P<0.0001). No difficulty was encountered from scarring in the five patients who underwent nerve spring radical retropubic prostatectomy following local anesthetic injection. Periprostatic injection of local anesthetic essentially eliminates pain from prostate biopsy. Nerve-sparing radical retropubic prostatectomy is not more difficult as a result.

Prostatic and central nervous system histoplasmosis in an immunocompetent host: case report and review of the prostatic histoplasmosis literature.

Histoplasmosis is a common cause of systemic mycosis in areas of the United States where it is endemic. Central nervous system and genitourinary histoplasmosis is rare, especially in immunocompetent hosts. We describe a case of disseminated histoplasmosis in a normal host that was associated with cerebral and prostatic histoplasmosis presenting as fever of undetermined origin, weight loss, and severe debilitating altered mental status. The patient subsequently developed acute renal failure that manifested as obstructive uropathy during antifungal therapy with amphotericin B. Transurethral resection of the prostate resulted in improved renal function during continuation of amphotericin B therapy. Pathological analysis of the prostate revealed necrotizing granulomas with intralesional fungal organisms. Blood and urine cultures were positive for Histoplasma capsulatum. Diagnostic issues and management are discussed. Treatment resulted in return of normal cognitive and motor function. This case is compared with the 8 previously reported cases of H. capsulatum prostatitis.

T-cell adoptive immunotherapy of metastatic renal cell carcinoma.

OBJECTIVES: To determine the feasibility and toxicity of the adoptive transfer of ex vivo-activated T lymphocytes that have been sensitized to autologous tumor vaccine in vivo. METHODS: Twenty patients with extensive metastatic renal cell carcinoma received systemic adoptive immunotherapy with autologous T cells in the absence of conjunctional interleukin-2 (IL-2) administration. Patients were vaccinated intradermally with irradiated autologous tumor cells and granulocyte-macrophage colony-stimulating factor as an adjuvant to stimulate an immune response. Inguinal lymph nodes draining the vaccine site were surgically removed, and the cells were stimulated with staphylococcal enterotoxin A followed by expansion in 60 IU/mL IL-2, and in some cases additionally stimulated with anti-CD3 monoclonal antibody and IL-2, to obtain a large number of cells. RESULTS: The staphylococcal enterotoxin A/IL-2 activation induced vigorous proliferation of T cells (median expansion 26-fold) that were a mixture of CD4 and CD8 T lymphocytes. Activated cells were infused intravenously at doses ranging from 2x10(9) to 9.5x10(10). There was minimal toxicity consisting of grade 1 or 2 fever and nausea, and the entire treatment was delivered as outpatient therapy. One patient had a partial response, one had a mixed response, and 8 had stable disease lasting at least 5 months. CONCLUSIONS: Adoptive transfer of ex vivo-activated, tumor vaccine-primed lymph node cells is feasible and is associated with minimal toxicity when used alone. These results warrant further study in a Phase II trial.

Altered expression of RET proto-oncogene product in prostatic intraepithelial neoplasia and prostate cancer.

BACKGROUND: The RET proto-oncogene encodes a protein that belongs to the tyrosine kinase growth factor receptor family. Germline point mutations in RET are found in individuals with multiple endocrine neoplasia (MEN) syndromes, and gene rearrangements have been reported in papillary thyroid cancers. We recently identified transcripts of the RET proto-oncogene in human prostate cancer xenografts and prostate cancer cell lines by means of reverse transcription-polymerase chain reaction analyses. The purpose of this study was to investigate Ret protein expression in human prostate tissue. METHODS: Ret protein expression was evaluated immunohistochemically in formalin-fixed, paraffin-embedded whole-prostate sections. The prostate specimens were obtained from 30 patients with prostate cancer after radical prostatectomies. Ret protein expression was compared in tumor foci and benign prostatic tissue. Medullary thyroid carcinoma tissue associated with an MEN syndrome and papillary thyroid cancer tissue served as positive controls. RESULTS: Ret appeared to be overexpressed in high-grade (histopathologically advanced) prostatic intraepithelial neoplasia (PIN) and prostate cancer when compared with its expression level in benign prostatic secretory epithelium. In addition, there was an apparent increase in Ret protein expression with decreased cellular differentiation, i.e., increasing Gleason pattern. CONCLUSION: Expression of the RET proto-oncogene in benign prostatic epithelium, high-grade PIN, and histopathologically advanced prostate cancer suggests that RET may play a role in the growth of both benign and neoplastic prostate epithelial cells.

The changing management of ureterovaginal fistulas.

A retrospective review of 20 ureterovaginal fistulas in 19 patients treated within the last 20 years was done. All fistulas developed after gynecological procedures. The ureterovaginal fistulas resolved in all 7 patients in whom a self-retaining internal stent was placed in either a retrograde (5) or antegrade (2) manner for a minimum of 4 to 8 weeks. In contrast to the literature, it is concluded that modern endourological treatment will result in resolution of a ureterovaginal fistula if passage of a suitable internal stent is feasible. Every effort should be made to treat a ureterovaginal fistula endourologically rather than resort to an open operation.

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.

Use of electrocoagulation in the treatment of vesicovaginal fistulas.

The role of electrocoagulation for the treatment of vesicovaginal fistulas has not been clearly defined. To determine the use of this therapeutic modality, 15 cases of fistulas treated with electrocoagulation were retrospectively reviewed. Fulguration represented the primary treatment in 12 patients and the secondary treatment in 3 after an initial attempt at open surgical closure failed. In all instances fistula size was estimated to be 3.5 mm. or less. A Bugbee electrode, which was inserted into the fistula either cystoscopically or vaginally, was used to destroy the epithelial lining of the fistula tract. Following the procedure the bladder was decompressed with a large indwelling Foley catheter for at least 2 weeks. Fulguration was successful as the sole treatment modality in 9 of 12 patients (75%) and as an alternative intervention after failure of an open surgical repair in 2 of 3 (66%). Therefore, 11 of the 15 women (73%) had complete resolution of the fistulas with this technique. We conclude that fulguration is usually effective in managing patients with vesicovaginal fistulas a few millimeters in size or less. This technique should be used as an initial treatment for appropriately selected patients and in women with small residual fistulas after open surgical failure.

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.

Delayed spontaneous rupture of an ileocolonic neobladder.

A case of delayed spontaneous rupture of an ileocolonic neobladder and subsequent peritonitis 4 years after the initial operation is reported. Many of the features of this case are similar to those noted in recent reports of spontaneous rupture of an augmented bladder and it is postulated that the etiology is the same.

Partial cystectomy.

Partial cystectomy remains an uncommonly performed procedure in the urologist's armamentarium. Historically, it has had a limited role in the treatment of bladder cancer because of the variable reported success rate and because of the high success rate of local endoscopic excision. When patients with muscle-invasive lesions are appropriately selected, 5-year survival rates following partial cystectomy approximate those of radical cystectomy in the treatment of transitional-cell carcinoma while preserving a physiologically functioning bladder. Therefore, not only does partial cystectomy represent a valuable treatment option, but it appears to be the procedure of choice for local muscle-invasive transitional-cell carcinoma of the bladder when careful selection criteria are utilized. Future studies are needed to define its precise role in affording bladder preservation when used in association with adjuvant chemotherapy. Partial cystectomy also remains a surgical option for a variety of less common benign and malignant lesions of the bladder.

Factors influencing the outcome of a no incision endoscopic urethropexy.

A urethropexy without incision has been used in 108 women with a minimum of one year follow-up evaluation. Most of the patients (81 percent) experienced postoperative urinary retention, with the mean period of retention being 22 days. The cure rate was 81.5 percent. The technique was successful in women with grade I stress urinary incontinence (97 percent), but not as effective in women with high grade stress incontinence (45.5 percent in women with grade III stress urinary incontinence). The success rate, therefore, correlated significantly with the grade of incontinence (p less than 0.001). It is noteworthy that there were no failures in 36 women who were premenopausal and the cure rate of 72 percent in the postmenopausal group represented a significant reduction (p less than 0.001). The approach without incision is often effective in patients who have failed previous anti-incontinence procedures, with a cure rate of 82 percent in 22 women in this category, but most patients with a successful outcome in the more complex instances of stress urinary incontinence were also noted to be premenopausal. These data suggest that the success of the repair is dependent on the strength and integrity of the vaginal mucosa. When using the no incision technique, it is advisable to avoid the use of foreign body material in the suprapubic stab sites because of the high incidence of infection and tender nodules.

Treatment of osseous metastases secondary to renal cell carcinoma.

Osseous metastases occur in 25 to 50% of the patients with metastatic renal cell carcinoma. We retrospectively reviewed our experience with 14 patients who underwent 20 palliative orthopedic procedures for treatment of bony metastases secondary to renal cell carcinoma. Of the patients 6 presented after nephrectomy (group 1) and 8 presented initially with osseous metastases (group 2). Only 1 of the group 2 patients underwent adjunctive nephrectomy. Overall, 5 of 14 patients (36%) presented with fracture and 9 of 14 (64%) presented with impending fracture. Five patients required multiple procedures. A total of 7 lesions had been previously treated with external radiation. Of the 20 orthopedic procedures 17 (85%) resulted in significant functional improvement and 18 (90%) resulted in significant relief of pain. There were 4 major complications in the series, including 2 culminating in amputation. Average survival after palliative orthopedic procedures was 22 months (range 7 to 64 months) with a 1-year survival rate of 58%. Orthopedic palliation of osseous metastases from renal cell carcinoma is effective, and our experience indicates that the majority of renal cancer patients with bone metastases will survive long enough to benefit from palliative orthopedic procedures.

A dynamic dual isotope radionuclear method of quantifying penile blood flow.

A new radionuclear method of quantifying arterial and venous blood flow of the penis is described. The technique is based on the simultaneous recording of the change in blood volume and venous outflow in the flaccid and erect states, which is produced pharmacologically. The change in penile blood volume is determined by measuring the change in the technetium-labeled red blood cell activity with time. Venous outflow is recorded with a xenon washout technique. The isotope data are used to compute arterial and venous flows with a complex computerized mathematical formula. Three basic blood flow patterns have been noted that distinguish normal patients from those with arterial insufficiency and venous leakage. The study is relatively easy and noninvasive to perform, and it appears to quantify penile blood flow accurately.

Through the eyes of women: the sexual and psychological responses of women to their partner's treatment with self-injection or external vacuum therapy.

We prospectively delineated and contrasted the sexual, marital and psychological responses of women to their partner's use of 2 treatments for erectile dysfunction: 1) self-injection of papaverine and phentolamine, and 2) vacuum tumescence therapy. The women were assessed at 5 points during a 12-month period with psychometric questionnaires and clinical interviews. Statistical analysis indicated that the women responded equally well to both treatments. They demonstrated significant increases in frequency of intercourse, sexual arousal, coital orgasm and sexual satisfaction. No significant changes were noted on the psychometric questionnaires. The women reported feeling more at ease in their relationships and characterized sex as more leisurely, relaxed and assured. Negative responses focused on the lack of spontaneity and hesitation about initiating sex. Self-injection and vacuum pump therapy restore potency in men and secondarily facilitate improved sexual function in women.

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.

A dual-radioisotope technique for the evaluation of penile blood flow during tumescence.

A technique is described for concomitant study of both arterial and venous penile blood flow during tumescence. Dual-isotope acquisition is started after labeling red cells in vivo with 99mTc. Xenon-133 in saline is then injected into the corpus cavernosum followed with vasoactive drugs to induce an erection. The resulting xenon and technetium time-activity curves are inputs for a one-compartment model. In 14 subjects, the average peak arterial flow rate (PAF) for normal males was calculated as 13.0 +/- 1.28 ml/min (avg +/- s.d.) compared to 16.1 +/- 5.14 and 5.02 +/- 1.78 ml/min for patients with venous leak (VL) or arterial insufficiency (AI), respectively. Peak venous flows (PVF) were 4.25 +/- 1.17, 12.1 +/- 3.75, and 3.78 +/- 1.00 ml/min for normal, VL and AL respectively. Al patients have significantly lower PAF than normal (p = 0.002) or VL patients (p = 0.018), and VL patients had significantly higher PVF than normal (p = 0.012) or Al (p = 0.018). The technique may be helpful in the study of impotence.

Evolution of endoscopic urethropexy: seven-year experience with various techniques.

The surgical techniques for correction of stress urinary incontinence continues to evolve particularly those utilizing the endoscopic approach. Various forms of endoscopic urethropexy have been performed in 142 women with a minimum of one-year follow-up. The cure rate for the entire series was 94 percent. In the last two years the no-incision technique was used whenever feasible (31 patients) with an identical cure rate of 94 percent. Varying degrees of urinary retention occurred in 58 percent and was even more prevalent following the no-incision technique (68%). Owing to the high incidence of urinary retention a punch suprapubic cystostomy is now used in most patients. We conclude that endoscopic urethropexy is an effective means of correcting stress urinary incontinence. The no-incision technique is associated with even less morbidity and a reduction in hospital stay without compromising the outcome.

Sexual, psychological, and marital impact of self-injection of papaverine and phentolamine: a long-term prospective study.

This prospective study assessed the long-term effects of self-injection of papaverine hydrochloride and phentolamine mesylate along several critical domains for 42 men and 26 partners. Over the course of one year, men were, on average, injecting themselves five times monthly, with 84% of these injections producing satisfactory erections. Treatment resulted in statistically significant improvements in quality of erection, sexual satisfaction, frequency of intercourse, and coital orgasm. The women also demonstrated significant improvement in sexual satisfaction, arousal, frequency of intercourse, and coital orgasm. Decreases in general psychiatric symptomatology were apparent for men but not for partners. The dropout rate was 57%. The common side effects of treatment were development of fibrotic nodules (26%), abnormal liver function values (30%), and bruising (19%). We conclude that self-injection should be considered among the accepted treatments for erectile dysfunction. It does appear to enhance the sexual lives of men and women when the treatment is efficacious and the couple is motivated to utilize it.

External vacuum devices in the treatment of erectile dysfunction: a one-year study of sexual and psychosocial impact.

This prospective study assessed the sexual and psychosocial effects of 12 months' use of an external vacuum device in the treatment of erectile dysfunction. Results showed that the external vacuum device produced erections sufficient for intercourse in 87% of the men in our sample. The dropout rate was only 20% over the 12-month period. Use of the external vacuum device was associated with improvements in men's and their partners' sexual functioning. These improvements included erections of better quality, increased partner arousal, and increased frequency of orgasm and sexual satisfaction for men and women. The external vacuum device was also associated with decreases in general psychiatric symptomatology for men. Similar improvements in psychological functioning were not found for partners. Side effects and factors in patient and partner acceptance of the external vacuum device are discussed.