Effects of senescence and citral on neuronal vacuolar degeneration in rat pelvic ganglia.

A significant part of the morbidity in elderly men involves pelvic organs and their autonomic neural regulation. Environmental stimuli also impair the structure and function of pelvic organs. One of these factors is citral, a widely-used cosmetic fragrance constituent, which causes severe prostatic hyperplasia in rats. In this study, we assessed the effect of topical administration of citral (30 days) on the morphology of pelvic ganglia (PG) in young adult and old Wistar rats. Neuronal vacuolar degeneration with preserved nuclei of PG neurons was observed in untreated senescent, but not young rats. Citral significantly increased the rate of vacuolated neurons in old rats (from 3 to 14%), but only slightly in young ones (from 0 to 0.5-0.3%). Similar lesions were not found in inferior cervical or celiac ganglia, in either group. This shows that environmental stimuli enhance age-related processes of vacuolar neuronal degeneration in PG, and may contribute to the dysfunction of pelvic organs in the elderly.

Metachronous renal cell carcinoma metastasis to the contralateral adrenal gland.

OBJECTIVES: Metachronous metastasis of renal cell carcinoma to the contralateral adrenal gland is very rare. We review our experience with 5 such patients and compare it with reports in the literature. METHODS: The records of all 350 patients who underwent nephrectomy for renal cell carcinoma in our center between 1975 and 1992 were reviewed. Five patients were found to have had solitary metachronous metastases to the contralateral adrenal gland on follow-up. RESULTS: The adrenal metastasis was discovered 18 to 210 months (mean 66.8) after nephrectomy. In 2 patients the lesion was found incidentally on routine computed tomography scan; in the other 3 patients, diagnosis was by ultrasonography, performed because of flank pain and weight loss or routine follow-up. All patients underwent adrenalectomy. Survival ranged from 8 to 64 months (mean 36.4); 3 patients had no evidence of disease at 42, 44, and 64 months postoperatively, and 2 patients died of pulmonary metastasis at 8 and 24 months. Analysis of the clinical data of our 5 patients together with the 9 we found in the published reports revealed that the mean interval between nephrectomy and the appearance of adrenal metastasis was shorter in the patients who died. CONCLUSIONS: The results of adrenalectomy for metachronous metastasis of renal cell carcinoma to the contralateral adrenal gland are unpredictable. The prognosis is somewhat better when the mean interval between the nephrectomy and the appearance of the adrenal metastasis is longer than 18 months. We recommend adrenalectomy because long-term survival is expected in some of these patients.

Local microwave hyperthermia and intravesical chemotherapy as bladder sparing treatment for select multifocal and unresectable superficial bladder tumors.

PURPOSE: The role of a combined regimen of local hyperthermia and topical chemotherapy in patients with multifocal and recurrent superficial bladder tumors not curable by transurethral resection was evaluated in a neoadjuvant organ sparing clinical study. MATERIALS AND METHODS: A total of 19 patients with multifocal, superficial grades 1 to 3 bladder tumors that recurred after intravesical chemoprophylaxis or immunoprophylaxis underwent local combined administration of microwave induced hyperthermia and intravesical chemotherapy as a debulking approach. Due to extensive superficial involvement of the bladder walls complete transurethral resection of all tumors seemed technically unfeasible in all cases and radical cystectomy was considered the treatment of choice. Endovesical hyperthermia at 42.5 to 46C was delivered using the SB-TS 101 system, based on a microwave transurethral applicator that irradiates the bladder filled with a circulating solution of mitomycin C. Patients underwent 8 weekly 1-hour sessions on an outpatient basis without anesthesia. When possible, after treatment patients underwent transurethral resection of residual tumors and all suspicious areas. RESULTS: After treatment transurethral resection appeared to be feasible and curative in 16 patients (84%). Histological study revealed complete and partial responses in 9 (47%) and 7 (37%) cases, respectively. Due to extensive residual tumors radical cystectomy was performed in 3 patients (16%). At a median 33-month followup 8 superficial transitional tumor recurrences were documented and easily eradicated by transurethral resection or laser therapy in patients in whom the bladder had been saved. CONCLUSIONS: Microwave induced hyperthermia combined with intravesical mitomycin C seems to be a feasible, safe and elective approach for conservative treatment of multifocal and recurrent superficial bladder tumors when other treatment strategies have failed.

Role of chronic inflammation in the promotion of prostatic hyperplasia in rats.

PURPOSE: Chronic prostatitis is a common histopathological finding in prostatectomized patients. A possible interrelationship between the presence of leukocyte exudate and the extent of the hyperplastic lesions has been suggested. The aim of the present study was to analyze the effect of the immunomodulator compounds, Complete Freund Adjuvant (CFA) and cyclosporin A (CsA), administered alone or together with citral on the induction and extent of rat prostatic hyperplasia. MATERIALS AND METHODS: Adolescent Wistar rats (42 days old) were given citral alone or combined with CFA or CsA for one month. Semiquantitative analysis of the extent of the hyperplastic lesions was made with the histoscore protocol. RESULTS: CsA did not induce hyperplastic changes or abolish the ability of citral to promote hyperplastic changes or to affect the extent of the lymphocytic exudate in the stroma. CFA itself, however, had a proliferative action on the prostatic epithelium, and it augmented the hyperplastic changes induced by citral and even induced atypical transformations of the acinar epithelium. CONCLUSIONS: Immunoinflammatory stimulators might play a role in the prostatic epithelial cell growth and proliferation processes, most probably by modulation of the cytokine system.

[Gonadotropin-releasing hormone (GnRH) in selecting patients for varicocelectomy].

The gonadotropin-releasing hormone (GnRH) test was performed on 182 patients with various degrees of varicocele before and after low, inguinal, spermatic vein ligation, and on 18 controls. The levels of follicle-stimulating hormone (FSH) and luteinizing hormone, a synthetic GnRH (LH), were evaluated before and 45 minutes after intravenous injection of 100 mcg relisorm L. FSH levels increased more than 2-fold in 118 patients [64.8%] and LH levels increased more than 5-fold in 135 patients [74.1%]). In the control group the increase was less in all cases. Therefore, whenever FSH increased more than 2-fold and LH more than 5-fold, we considered the test positive (pathologic); On this basis the GnRH test was positive in 126 (69.2%) and negative (normal) in 56 (30.7%). Of the 126 with positive tests, only 32 (27.3%) still had a positive result 5-6 months after operation. There was correlation between a positive GnRH test and significant improvement in sperm parameters after varicocelectomy: of the 126 with positive tests before operation, sperm parameters improved in 87 patients (69%), while in the 56 patients with negative tests before operation, in only 7 (12.5%) was there improvement after correction. We conclude that a positive GnRH test indicates impairment of the hypothalamic-pituitary-gonadal axis caused by varicocele and could serve as a marker for surgical intervention with good prediction of outcome.

Correlation between semen parameters and retrograde flow into the pampiniform plexus before and after varicocelectomy.

OBJECTIVE: To compare, before and after repair of varicocele, the semen parameters (SP) in relation to the persistence of retrograde vein flow. MATERIAL AND METHODS: We examined the correlation between semen characteristics and retrograde flow (RF) into the pampiniform plexus in 158 patients with varicocele, before and after low inguinal spermatic vein ligation. RESULTS: The results of the investigation before surgery showed that all patients had RF and also a decrease in quantitative and qualitative SP. After surgery an improvement was observed in SP and there was a decrease in RF as a function of time elapsing from surgery. One year after surgery, an improvement in SP in 136 (86.1%) patients was observed. In 14 (8.8%) no change was noted and in 8 (5.1%) there was a deterioration in SP. Comparison between increased SP and persistence of RF 1 year after surgery revealed that of the 136 patients who showed improvement in SP, 124 (91.1%) did not have RF. Of the 14 patients with no improvement in SP, 12 (85.7%) were free of RF and 9 patients with deteriorated SP and bilateral RF. Amongst 132 infertile men, the wives of 55 (41.6%) became pregnant. None of these 55 men demonstrate RF. CONCLUSIONS: These results revealed a significant correlation between the improvement of SP, pregnancy in patients' wives and disappearance of RF. These results may be considered as a parameter of successful varicocelectomy.

Type II ureteral triplication associated with ectopic ureter.

We report a case of type II ureteral triplication associated with ectopic ureter. The ureter, draining the upper renal segment, entered the vagina, and the other two ureters, draining the middle and lower renal segments, had joined and entered the bladder. The anatomic findings are compatible with those predicted by the Weigert-Meyer law. A thorough evaluation of such an anomaly is essential for effective management.

[Surgery for women with urethral diverticulum].

Urethral diverticulum in the female is an acquired lesion following infection of the para-urethral glands. Its symptoms are often nonspecific and only by increased awareness of this condition can delay in diagnosis be avoided. Radiologic imaging of the urethra allows diagnosis of this lesion and determination of its location, extent and the number of lesions. Complete surgical excision is the optimal therapy. In recent years 8 women with this condition were admitted aged 21-52 years. It had been an average of 11 months before their lesions were diagnosed. All had complete surgical excision without perioperative complications. In 5 a Martius labial fat pad was used to facilitate prompt healing of the urethral defect. 6 have been followed for over a year and are completely symptom-free. Judicious choice of surgical technique is required to reduce the rate of complications in the management of these lesions.

Citral and testosterone interactions in inducing benign and atypical prostatic hyperplasia in rats.

Citral is a monoterpene in wide use as an aromatic supplement in the cosmetics and food industries. Previous studies in our laboratory have shown that cutaneous application of citral on adolescent rats may induce benign prostatic hyperplasia (BPH)-like and even atypical hyperplastic changes in the ventral lobes. In the present study we investigate the possible interactions between citral and serum testosterone levels on the induction of hyperplastic changes in the ventral prostate of adolescent rats. In addition, the study includes a comparative analysis of normal intact rats showing circadian variations of serum testosterone levels and rats in whom this rhythmic pattern was abolished either by excessive supplementation of exogenous androgen or by castration. Our results demonstrate an induction of benign as well as atypical prostatic hyperplasia following citral application. The most severe atypical changes were noted in the citral-treated rats with high serum testosterone levels. Although the mechanism of action of citral is yet unknown, the present results suggest a synergism between citral and testosterone resulting in hyperplastic changes in the rat ventral prostate. In addition, the results reconfirm that serum testosterone levels fluctuate according to a circadian rhythm in intact young and adolescent male rats. The application of citral tends to lower the morning circadian peaks, and the circadian pattern was abolished in orchiectomized rats and in those treated with testosterone implants.

Penile edema and meatal ulceration after intravesical instillation with bacillus Calmette-Guerin.

Bacillus Calmette-Guérin (BCG) bladder instillation is an accepted treatment modality in the management of superficial transitional cell carcinoma but is associated with frequent side effects. A report of intravesical BCG-induced penile edema and meatal ulceration that occurred in 2 patients is presented. During induction therapy, both patients complained of progressive penile edema. In 1 patient the edema appeared after the second instillation and in the other after the fourth instillation. Edema was associated with ensuing meatal ulceration and enlarged inguinal lymph nodes. BCG instillation was aborted, and oral antituberculous treatment was initiated. There was no report of external spillage during the administration of BCG or of genital or urethral trauma during catheterization. Patients were treated at different clinics but with BCG of the same strain and batch. Symptoms continued for 6 weeks until they abated. Both patients were managed with oral antituberculous drugs for a period of 3 months. Adverse effects of BCG intravesical administration affect several organs in the genitourinary system. The penis and urethra may also be involved, presenting as penile edema and meatal ulceration. Physicians who administer BCG must be familiar with the possible complications and their appropriate management.

Dismembered pyeloplasty in children with and without stents.

OBJECTIVES: To assess the benefit of performing nonstented pyeloplasty in infants. METHODS: Forty-eight consecutive pyeloplasties were performed by two surgeons using different techniques, from 1987 to 1992. One used stents in all cases (23) and the other performed a nonstented anastomosis with external drainage (25 cases). Patients with specific indications for internal drainage, i.e. poor renal function, extreme pyelocaliectasis, were excluded from the study. Parameters of cost and complications were assessed. RESULTS: The group with stents had more febrile episodes, needed more antibiotics and were hospitalized twice as long as the nonstented group. Pre- and postoperative renal function was similar in both groups. CONCLUSIONS: Performing pyeloplasties in children without stenting the anastomosis is safe and cost-effective.

[Changes in semen after low inguinal spermatic vein ligation].

We examined semen characteristics of 128 patients prior to low-inguinal, spermatic vein ligation for varicocele and every 2 or 3 months over the course of a year. There was a higher sperm count 26 months after surgery, and after 68 months improved motility and a higher proportion of sperm with normal morphology. 10 months to 1 year after surgery there was improvement in all 3 parameters in 106 patients (82.8%), in 17 (13.2%) no change, and in 5 (3.9%) deterioration. Changes in sperm parameters (SP) were compared with retrograde flow (RF) into the pampiniform plexus 10-12 months after operation. Of the 106 patients with improvement in SP, only 14 (13.7%) had RF; of the 17 with no improvement, 14 (82.4%) had RF; and in all 5 in whom SP deteriorated there was bilateral RF. The study points to the necessity of continued follow-up of varicocele patients for at least a year after operation. Further management should be based on postoperative changes and the presence or absence of RF and improvement in SP.

Vacuum therapy combined with psychotherapy for management of severe erectile dysfunction.

We used vacuum therapy in combination with psychotherapy in 145 patients with different types of erectile dysfunction (ED). The age range was 24-82 years (average 53.4 +/- 2.7 years). The patients were divided into 3 groups according to the type of ED: 26.2% psychogenic, 36.5% organic, 37.2% mixed. All received the same treatment. Improvement in sexual function parameters, both subjective (adequate erection, spontaneous erection) and objective (penile brachial index, maximal rigidity of penis) were compared among the groups. The best results were noted in the psychogenic and organic ED patients. Of the 38 patients with psychogenic ED, 12 (31.5%) had coitus after treatment without any intervention, 23 (60.5%) had coitus with help of the vacuum constriction device (VCD). Of 53 patients with organic ED, 11 (20.7%) had coitus without any intervention, and 39 (73.5%) had coitus with help of the VCD. Of the total study population (n = 145), 31 (21.3%) had coitus without any intervention, 98 (67.5%) had coitus with help of the VCD. In 16 (11%) cases, there was no improvement in either subjective or objective parameters of sexual function.

Metachronous bladder tumors in patients with upper urinary tract transitional cell carcinoma.

Sixty-nine patients who underwent nephroureterectomy for upper urinary tract transitional cell carcinoma were included in the study. The following data were collected for each patient: grade and stage of renal/ureteral tumor, tumor location, timing of tumor appearance and recurrence in the bladder, grade and stage of each of the recurrent tumors, and number of recurrences. Follow-up ranged between 2 and 15 years. Thirty-three patients (47.8%) developed metachronous bladder tumors. The appearance of the bladder tumors was related to tumor grade and multifocality of the upper urinary tract TCC. Of the 33 patients, 19 had 1 tumor appearance in the bladder, 6 had 2 recurrences, and 8 had 3 recurrences. The 5-year survival rate for patients with no subsequent bladder tumors was 57% compared to 22% for those who had subsequent tumors. It is concluded that the appearance of bladder tumors following nephroureterectomy characterizes a group of patients with biologically more active disease with unfavorable prognosis.

Effect of improved diagnosis of renal cell carcinoma on the course of the disease.

The impact of the improved diagnosis of renal cell carcinoma (RCC) on the course of the disease was evaluated in 188 patients who were diagnosed and treated at a single medical center. Sixty-seven patients (group A) who had undergone nephrectomy between 1979 and 1983 for RCC initially diagnosed by intravenous pyelography (IVP) were compared with 121 patients (group B) who had undergone nephrectomy between 1983 and 1989, diagnosed by ultrasound and/or computed tomography (CT) scan. Incidental asymptomatic tumors were found in 18 of 67 (26.9%) group A patients and in 57 of 121 (47.1%) group B patients (P < 0.001). The incidence of small tumors of < 5 cm in diameter was significantly lower in group A compared to group B (25.4% vs. 47.9%, respectively, P < 0.01). The disease-free 5-year survival rate for group A was 40% compared to 80% for group B. It is concluded that the introduction of modern imaging techniques has improved the survival of patients with RCC and decreased the progression rate of the disease.

A comparison between digitally-guided fine needle aspiration and ultrasound-guided transperineal core needle biopsy of the prostate for the detection of prostate cancer.

OBJECTIVE: To prospectively examine the accuracy of fine needle aspiration (FNA) for the detection of prostate cancer. Ultrasound-guided core needle biopsy of the prostate was used as the standard to which the FNA results were compared. PATIENTS AND METHODS: One-hundred patients who had been referred for urological evaluation were suspected of having prostate cancer on the basis of digital rectal examination (DRE) and/or transrectal ultrasound (TRUS). All were further evaluated by digitally guided transrectal FNA and by TRUS-guided transperineal core needle biopsy. RESULTS: Prostate cancer was identified in 54 patients by core needle biopsy and in 45 by FNA. The sensitivity of FNA was 81% and both specificity and positive predictive value were 98%. CONCLUSION: FNA is easily performed, has negligible morbidity and offers prompt results. These data suggest that FNA is a reasonable initial diagnostic procedure for the detection of prostate cancer. Core needle biopsy may be reserved for patients with negative cytology who are clinically suspected of having prostate cancer. In selected patients, FNA may be used as an alternative to core needle biopsy for diagnosis, treatment planning and follow-up.

Rapid tumour recurrence following cessation of long-term treatment with intravesical thiotepa.

OBJECTIVE: To report tumour recurrence related to cessation of long-term therapy with thiotepa. PATIENTS AND METHODS: A group of 12 patients with low grade (I-II), low stage (TA-T1) transitional cell carcinoma of the bladder were included in the study. All patients had been treated with intravesical thiotepa for a period ranging from 24 to 71 months and none had had a recurrence for a period of between 15 and 51 months. After referral to this department all the patients were withdrawn from thiotepa therapy. RESULTS: All the patients developed bladder tumours within 6 months of cessation of therapy. The recurrent tumours were grade II in 10 patients and grade III in two patients. Eight patients had stage TA and four had stage T1. All responded to bacille Calmette-Guérin therapy and none had tumour recurrence on follow up at 24 months. CONCLUSION: Meticulous follow-up of patients is indicated soon after the cessation of long-term therapy with thiotepa.

Immediate vasoactive effect of citral on the adolescent rat ventral prostate.

The vasoactive effect of a fragrance compound, citral, on rat ventral prostate is presented. A combined method of Indian-ink perfusion and postfixation transparency was used. One single dose of citral applied on the back skin of the rat induced an immediate triple response-like effect on the prostatic vascular bed. A slight vasodilatation appeared already after 2 1/2 min, followed by a marked vasoconstriction process after 5-min postcitral administration. Toward the period of 10 min, a second vasodilatation process was noted which persisted for the following 24 hr of observation. This study has demonstrated that changes in the microvascularization of the rat prostate can be estimated by counting the number of carbon-stained blood vessels. The results obtained by this technique are closely related with the findings in the vascular network profile of the macroangiographic observations. The mechanism of action of citral on the microvascularization of the rat ventral prostate is yet unknown. Based on the present findings, we suggest that the neoplastic capacity of citral upon the prostatic epithelia is activated via a nonspecific inflammatory reaction modulated either by local release of neurotransmitters or throughout a direct effect of citral on the endothelial cells.