Dov Engelstein

Incidental small renal tumors accompanying clinically overt renal cell carcinoma

We searched 66 kidneys with renal cell carcinoma for subcapsular or intraparenchymal small nodules in the apparently normal-appearing portion of the kidney. Differentiation between adenoma and carcinoma was done according to histological characteristics. Of the 66 kidneys 20 (30 per cent) contained a total of 58 small nodules ranging from 1 to 15 mm. in diameter. In 9 kidneys the lesions were consistent histologically with carcinoma, in 7 with adenoma and in 4 with carcinoma plus adenoma. Thus, 13 of the 66 kidneys (19.7 per cent) contained small carcinoma. In view of the high incidence of small carcinoma accompanying clinically overt renal cell carcinoma, we suggest that the indications for partial nephrectomy in the management of renal cell carcinoma should be reevaluated.

Clinical and pathological findings in prostates following intravesical bacillus Calmette-Guerin instillations

The prostates of 36 patients who were treated with intravesical bacillus Calmette-Guerin were evaluated by digital rectal examination and transrectal ultrasonography. When abnormal palpatory and/or ultrasonographic findings were detected, core needle biopsies from the suspicious areas were performed. Of the 36 patients 20 underwent biopsies of the prostate. Pathological findings revealed typical granulomas in 8 patients (3 caseating and 5 noncaseating multifocal granulomas). Nonspecific chronic prostatitis was noted in 4 patients and benign prostatic hyperplasia was noted in 8. The number of bacillus Calmette-Guerin instillations ranged from 6 to 19. The interval from initiation of therapy to biopsy ranged from 1.5 to 14.5 months. Caseating granulomas were found during the early course of bacillus Calmette-Guerin instillations (1.5 to 3.0 months), whereas noncaseating granulomas were detected at later stages (4 to 14.5 months). These findings present a high incidence of granuloma formation in patients treated with intravesical bacillus Calmette-Guerin. The duration of therapy is a determinant factor in the induction of granuloma type.

The Effect of Intravesical Bacillus Calmette-Guerin Therapy on the Upper Urinary Tract

A total of 66 patients with low grade, low stage transitional cell carcinoma of the bladder who were treated with intravesical bacillus Calmette-Guerin (BCG) underwent cystourethrography to detect vesicoureteral reflux. BCG was instilled weekly for 6 weeks and monthly thereafter for up to 24 months. Whenever vesicoureteral reflux was found or morphological abnormalities were detected on excretory urography (IVP) an isotope renal scan was performed to evaluate the relative renal function. Vesicoureteral reflux was found in 13 patients (19.7%): 10 had grades 1 and 2A, and 3 had grade 2B reflux. The number of BCG instillations ranged from 8 to 22. IVPs were normal in 11 patients. In 2 patients mild unilateral dilatation was present before BCG instillations, and this remained unchanged during and after therapy. None of the 13 patients with vesicoureteral reflux had IVP features suggestive of urinary tuberculosis. In 11 patients the refluxing renal systems had normal relative renal function (50 to 55%). Two patients had a decrease to 40% of the relative renal function with normal IVPs, suggesting a nonBCG related cause. We conclude that BCG therapy is safe in patients with minimal reflux.

Urinary tract infection in men younger than 45 years of age: is there a need for urologic investigation?

OBJECTIVES To determine in a prospective study whether urinary tract infection (UTI) in men younger than 45 years of age is associated with anomalies of the genitourinary tract that necessitate additional urologic evaluation. UTI in young men is uncommon. In these patients, it is customary to follow the same policy as that for children or older men and to routinely perform urologic investigations. METHODS Twenty-nine consecutive, otherwise healthy, male patients aged 16 to 45 years (mean 30.5) were hospitalized for a first event of acute UTI. All patients underwent an imaging evaluation, including ultrasonography and intravenous urography. Those with macroscopic hematuria underwent cystoscopy. Uroflowmetry was performed at least 1 month after recovery, and patients with a maximal flow rate of less than 15 mL/s underwent a pressure flow study. RESULTS Significant urethral stricture was excluded in all patients. Twenty-seven patients (93%) had a postvoid residual urine volume of less than 20 mL, and only two had values of 120 and 200 mL. The imaging and cystoscopic evaluation demonstrated a normal urinary tract in all patients. The maximal urinary flow rate was greater than 15 mL/s in 22 patients (76%) and lower than 15 mL/s in 7 patients (24%). In the latter group, urodynamic investigations, including free flowmetry and/or pressure flow study, revealed normal lower urinary tract function in 6 patients and a bladder outflow obstruction in 1 (3%). CONCLUSIONS A first event of UTI in men younger than 45 years is usually not associated with significant structural or functional urinary tract abnormalities. Therefore, no radiologic, endoscopic, or urodynamic investigation is required.

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.

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.

Orthotopic model of renal cell carcinoma.

A human renal cancer was first established in continuous culture in 1962. Currently, there are well over 100 different characterized renal cancer cell lines derived from both primary and metastatic renal cell carcinomas (RCCs) (1-3). The biological phenotype of cultured renal cancer cells typically includes a sustained and essentially unlimited growth capacity, a lack of contact inhibition and anchorage dependence, a capacity to form tumors in athymic mice, and an aneuploid karyotype including nonrandom chromosomal abnormalities (1,2). The antigenic phenotype of RCCs as determined by monoclonal antibodies (mAbs) generated against cell-surface glycoproteins, glycolipids, and blood-group antigens of renal cancers provide a series of phenotypic markers which characterize these tumors (4-6). Many of these mAbs also react with the proximal tubule portion of the human nephron, confirming earlier studies indicating that >90% of renal cancers derive from epithelial cells of the proximal tubule (7,8). While established RCC cell lines have frequently been analyzed for molecular defects, their greatest utility has been to screen combinations of chemotherapeutic and biologic agents for antiproliferative activity (9-12). Short-term cultures of renal cancer cells derived from fresh tumor specimens have similarly been used to screen drugs (13), but inhibitory effects in vitro have not been shown to predict a response in vivo (i.e., in human patients).