Total pelvic exenteration with preservation of fecal continence.

Total pelvic exenteration may be required in the management of locally advanced or recurrent pelvic malignancy. Although prolonged survival may be achieved, the morbidity of this procedure is substantial. Many of the complications associated with total pelvic exenteration are related to the perineal wound, the necessity for two cutaneous stomas, and the creation of a empty pelvis that often has been previously irradiated. In selected cases, perineal preservation with restoration of coloanal continuity may significantly reduce postoperative morbidity. We report four cases of recurrent pelvic malignancy treated by total pelvic exenteration with preservation of fecal continence.

Carcinoma of prostate in men aged fifty and under: therapeutic options.

We made a retrospective study of 20 men, aged fifty or under, with adenocarcinoma of the prostate to evaluate presenting symptoms, stage, grade, and therapeutic results. Sixty-five percent were found to have extracapsular spread of disease (Stage C or D). The therapy used was one or a combination of three types: radical prostatectomy, radiation therapy, and hormonal manipulation. Five of 6 patients with Stage B disease and 3 of 6 patients with Stage C disease were treated with radiation therapy. The other Stages B and C patients underwent radical prostatectomy. In all 5 of Stage B patients receiving radiation, therapy failed; the mean time to tumor recurrence was 3.2 years. Two of 3 patients with Stage C disease died of metastatic disease within three years of receiving radiation. The 4 patients (Stages B and C) who underwent radical prostatectomy are free of disease. There was a statistically higher failure rate among the radiation therapy patients with Stages B and C disease than among the surgical patients (X2 = 8.4, p less than 0.1).

Multicenter study of superficial bladder cancer treated with intravesical bacillus Calmette-Guerin or adriamycin. Results of long-term follow-up.

We evaluated 158 cases of patients with superficial bladder cancers (Stages Ta, T1, and Tis). These cases were treated with either intravesical bacillus Calmette-Guerin (BCG) (Tice strain) or Adriamycin (ADR), in a multicenter, nonrandomized study. One hundred thirty-one of these patients were followed up; the results continue to show a higher percentage of initial complete remissions with BCG (68%) than with ADR (57%). With additional therapy, both BCG and ADR achieved complete remission in 83 percent of the patients. When 7 failures with patients taking ADR were switched to BCG and the disease cleared, the rate of complete remission for BCG rose to 85 percent. The recurrence rate per 100 patient-months was only slightly different for BCG (0.9) and ADR (0.8). The percentage of progressions continued to be higher for BCG (8%) than for ADR (5%). Cystectomies were performed in 2.5 percent of the BCG patients. Using the Cox regression model with covariates, we found drug treatment, tumor grade, and sex to be statistically significant in determining failures throughout the protocol. Although both BCG and ADR were effective over the course of the study, BCG is the drug of choice for residual tumor (Stages T1 and Tis).

Interstitial cystitis treated with intravesical doxorubicin.

Three patients with interstitial cystitis diagnosed on the basis of clinical symptoms, classic endoscopic findings, and a typical histologic picture were treated with intravesical doxorubicin. All 3 patients showed remarkable improvement, as manifested by complete clearance of irritative bladder symptoms and healing of ulceration. Doxorubicin therefore may be the breakthrough drug for interstitial cystitis.

Multicenter study of superficial bladder cancer treated with intravesical bacillus Calmette-Guérin or adriamycin.

We evaluated 155 patients with superficial bladder cancers (Stages Ta, T1, and TIS) and treated them with either intravesical bacillus Calmette-Guérin (Tice strain) (BCG) or doxorubicin hydrochloride (Adriamycin), in a multicenter nonrandomized study. At present 140 of these patients in treatment Groups I and II are being followed up. With additional follow-up, BCG continued to produce a higher percentage of complete remissions (71%) than doxorubicin (54%). The percentage of incomplete remission with BCG (7%) was half that with doxorubicin (14%). Half of the patients whose initial therapy failed had complete remission after additional therapy. However, for patients with recurrence, additional follow-up shows a recurrence rate per 100 patient-months for BCG (1.0) only slightly lower than that for doxorubicin (1.1). The percentage of progressions continued to be higher with BCG (8.5%) than with doxorubicin (5%), but the difference between these results for the two drugs proved slightly less than we reported previously. Of the patients in this study, 2.5 percent (all treated with BCG) required cystectomy. A comparison of the results of our study with those of 13 other studies using BCG to treat bladder cancer indicates that therapy beyond an initial course of 6 weekly treatments increases the percentage of complete response. All of the studies showed that the greatest improvement in percentage of complete response occurred with the second course of treatment. The value of maintenance therapy cannot yet be determined, since few studies have used that protocol. The percentage of patients requiring cystectomy in studies with fewer than 20 treatments was 2.2 times higher than in studies with more than 20 treatments.

Does bacillus Calmette-Guérin immunotherapy accelerate growth and cause metastatic spread of second primary malignancy?

In our study, 29 of 150 patients with bladder cancer also had other associated primary malignancies, 10 of which were manifested after intravesical treatment with bacillus Calmette-Guérin (BCG). Second primary malignancies developed in 5 of these patients within three months of the start of BCG therapy. All 5 showed acceleration of the second primary tumor, and distant metastatic lesions developed in 4. In the other 5 patients nonbladder primary malignancies developed eight months or more after intravesical BCG therapy started, but did not show acceleration or spread. Twenty patients with other primary malignancies that had developed months to years before intravesical therapy did not show acceleration or spread of those tumors. We have seen enough cases of patients who received intravesical BCG at the time of growth and spread of second primary malignancies to warrant concern. Animal and human studies of BCG use for treatment of malignancy indicate that the temporal relationship between the starting point of tumor development and the starting point of BCG treatment is crucial in determining whether BCG will eradicate or exacerbate the tumor. We have therefore instituted a change in our treatment until the question of whether or not BCG causes the appearance and spread of these second malignancies is answered.

Superficial bladder cancer treated with intravesical bacillus Calmette-Guérin or adriamycin: follow-up report.

We evaluated 139 patients with superficial bladder cancer (Stages Ta, Tl, and TIS) and treated them with either intravesical bacillus Calmette-Guérin, Tice strain (BCG), or doxorubicin hydrochloride (Adriamycin [ADR]) in a nonrandomized, multicenter study. Our follow-up study comprises 135 of these patients. Of these patients, 78 tumors were completely resected, and 61 were incompletely resected. When a proportional-hazards model (Cox) was applied, there was a statistically significant difference between the recurrence rates for the two drugs. On the basis of recurrence rates per 100 patient-months, both BCG (1.2) and ADR (0.9) worked well with completely resected tumors. However, for incomplete resections, the recurrence rate for BCG (0.9) was less than half that for ADR (1.9). The overall recurrence rates were 1.1 and 1.3 for BCG and ADR, respectively. There have been 42 failures of treatment with either BCG or ADR. We defined failure as any recurrence of tumor; progression of the cancer in stage, grade, tumor number or size; or any residual tumor after 18 treatments (14 months of therapy). As to the failures in patients whom we followed up, and whose treatment was either switched from ADR to BCG or continued on further BCG treatment, 53 per cent have achieved complete remission. Complete remission for BCG and ADR were 76 per cent and 52 per cent, respectively. Of the various factors considered in the study, only tumor grade and treatment drug were statistically significant. The cystectomy rate was 1 per cent for BCG-treated patients and 0 for ADR-treated patients.

Superficial bladder cancer treated by intravesical bacillus Calmette-Guerin or adriamycin: multicenter study interim report.

One hundred sixteen patients with superficial bladder cancers (Stages Ta, T1, and TIS) were evaluated and treated with either intravesical bacillus Calmette-Guerin [Tice strain] (BCG) or doxorubicin hydrochloride (Adriamycin [ADR]), in a multicenter study. One hundred nine of these patients currently have follow-up. Of these, 54 were completely resected and 55 incompletely resected. For complete resections, based on recurrence rates per 100 patient months, both BCG (0.22) and ADR (0.91) worked well, although BCG had a slightly lower recurrence rate. However, for incomplete resections, BCG (0.20) had a markedly lower recurrence rate than ADR (2.52). Eighteen patients failed initial treatment, with either BCG or ADR. All have been placed on long-term therapy schedules. Of the 12 failures who currently have follow-up, 11 (92%) have either partially or completely responded with additional intravesical therapy. No patients in this study have yet required cystectomies.

Correlation of histopathological, cytological and flow cytometric findings in neoplastic and nonneoplastic lesions of the bladder.

Biopsy diagnosis, urine cytology and flow cytometry features of urine and bladder washings were compared in 81 cases of benign and malignant bladder disease. Some patients were followed by urine cytology and flow cytometry during treatment of tumors. There was a good correlation of the 3 parameters in relatively high grade tumors (II and III) but an inconsistent appearance of cells in the urine diagnosable by either urine cytology or flow cytometry for low grade lesions. High grade flat neoplasms may be detectable by urine cytology and flow cytometry before they are visible on endoscopy. Flow cytometry may indicate urothelial proliferation before it is apparent on urine cytology. Exfoliative benign lesions are diagnosed readily by the combination of urine cytology and flow cytometry. In benign and malignant lesions shedding of viable cells and, therefore, accessibility to urine cytology and flow cytometry are inconsistent. The need for repeated examinations in the case of low grade lesions suggests that the method is not reliable for single test screening programs but it is a valuable means of followup in cases of suspected or diagnosed disease.

Tissue polypeptide antigen (TPA) as a predictor for genitourinary cancers and their metastases.

Tissue polypeptide antigen (TPA) is an oncofetal antigen found in human malignant tumors of various origins. We used radioimmunoassay to determine TPA levels in a total of 150 serum samples from 88 patients with different types of genitourinary cancers. The serum TPA level among cancer patients of all stages combined was higher than in normal healthy controls (p less than 0.05). However, when the patients with metastases were excluded from the analysis, the TPA titer was not significantly different from those of the normal controls. The difference in serum TPA between patients with local disease and patients with metastatic lesions was highly significant (p less than 0.0001). The serum TPA levels were significantly decreased in patients who responded to treatment; the levels were significantly increased in those who progressively became worse.

Screening for urinary tract infection using Bac-T-Screen bacteriuria device.

The Bac-T-Screen was used to process 795 urine specimens. Tests for urine specimens took slightly more than two minutes. The Bac-T-Screen predicted with 99 per cent accuracy if a specimen was negative for bacteriuria or pyuria. Thus, approximately one half of all carefully collected urine specimens need no further laboratory culture. In addition, the Bac-T-Screen detected bacteriuria with a sensitivity of 96 per cent at the 10(5) CFU/ml level of probability. Pyuria (1 +) was detected with a sensitivity of 98 per cent. The Bac-T-Screen can be used in an office practice as well as in the clinical laboratory.

Effects of calcium and verapamil on vesicourethral smooth muscle of rabbits.

Isolated smooth muscle strips from the rabbit bladder body, bladder base, and proximal urethra were contracted with ionic calcium (Ca2+) alone and with the calcium-selective ionophore A23187, acetylcholine, norepinephrine, adenosine triphosphate (ATP), and direct electrical stimulation. The effects of Ca2+ and the calcium entry blocker verapamil on spontaneous muscle activity and on contractions induced by these agonists were examined. Ca2+ -free Tyrode's solution and verapamil, 1 x 10(-7)M and above, relaxed all of the vesicourethral smooth muscle strips. In addition verapamil, 1 x 10(-8) to 1 x 10(-6) M depending on the particular stimulant employed, noncompetitively inhibited smooth muscle contractions elicited by Ca2+, acetylcholine, norepinephrine, ATP, and direct electrical stimulation. It was concluded that transmembrane Ca2+ influx was important not only in the maintenance of tone and spontaneous phasic muscle activity, but also for the activation of contractions induced by all of the stimulants tested. The data also suggest that intracellular Ca2+ fraction(s) participate in the contractile responses to acetylcholine and norepinephrine challenge, but not to contractions evoked by ATP or electricity.

Percutaneous nephrostomy in a child with obstructive uropathy.

The advantages of percutaneous nephrostomy include (1) achieving rapid, safe drainage of an obstructed collecting system with use of local anesthesia and sedation rather than general anesthesia, and (2) facilitating use of antegrade pyelography under fluoroscopic guidance to determine the cause of the obstruction. In addition, during temporary diversion the functional status of the obstructed kidney can be evaluated. If function is adequate, a pyeloplasty or reimplantation of a ureter may supplant nephrectomy. Use of percutaneous nephrostomy is a relatively new technique for treatment of obstructive uropathy in children. In the case reported here of an 8-year-old girl with a duplicated right collecting system and distal obstruction of the upper pole ureter, the procedure offered a rapid and safe alternative to surgical insertion of a nephrostomy tube.

Adenomatous polyp of the bladder: a rare cause of hematuria in young men.

A 26-year-old black man presented with gross hematuria and was found to have a papillary lesion of the trigone of the bladder. The lesion proved to be an adenomatous polyp with prostatic-type epithelium. This type of neoplasia ordinarily is found in the prostatic urethra and has not been reported previously in the bladder. Adenomatous polyps are benign tumors and should be considered in the differential diagnosis of hematuria in young men.

Vesicourethral smooth muscle: function and relation to structure.

The effects of acetylcholine and norepinephrine on the longitudinal and circular smooth muscle strips from the rabbit bladder body, bladder base, and proximal urethra have been studied and compared. Based on the functional responses that were obtained, it was concluded that the vesicourethral structure can consist of three muscular systems. One system consists of the acetylcholine sensitive detrusor, the deep bladder base, and the longitudinal smooth muscle layer of the urethra. The second muscle system comprises the norepinephrine-sensitive detrusor muscle, the superficial bladder base, the bladder neck, and part of the longitudinal urethral smooth muscle. The third muscle system is the circular urethral musculature, unrelated to the detrusor circular muscle.

The effects of adrenergic agonists and antagonists on vesicourethral smooth muscle of rabbits.

The effects of alpha and beta adrenergic agonists and antagonists on isolated smooth muscle preparations from the rabbit bladder body, bladder base and proximal urethra have been studied. The predominance of alpha receptors in the proximal urethra and the bladder base was observed via contraction of these areas by norepinephrine and blockade by phentolamine. Alpha receptor-mediated contractile activity could be unmasked in the bladder body when beta receptors were blocked with propranolol. Isoproterenol, 1 X 10(-10) to 3 X 10(-7) M, had a strong, dose-related relaxant effect on the bladder body, but little effect on the bladder base or proximal urethra. Selective beta-2 agonists such as terbutaline, salbutamol and ritodrine elicited tissue responses similar to those of isoproterenol. The pD2 values for isoproterenol, terbutaline, salbutamol and ritodrine were 8.59, 7.87, 7.34, and 6.52, respectively. Dobutamine, a selective beta-1 agonist, failed to cause significant relaxation of these tissues. The nonselective beta receptor blocker, propranolol, and the selective beta-2 receptor blocker, butoxamine, competitively antagonized the relaxant effects of the four active beta agonists; however, atenolol, a selective beta-1 receptor blocker, was inactive. On the basis of the selective action of these agonists and antagonists, we concluded that beta-2 receptors mediate relaxation of the vesicourethral smooth muscles of the rabbit and the participation of beta-1 receptors in the areas is insignificant.

In vitro study of antispasmodic effects of dicyclomine hydrochloride on vesicourethral smooth muscle of guinea pig and rabbit.

Dicyclomine inhibition of acetylcholine-induced and barium chloride-induced isotonic contractions of the smooth muscle from three segments of the lower urinary tract (bladder body, bladder base, and proximal urethra) of the guinea pig and the rabbit was studied in vitro. In the guinea pig dicyclomine caused competitive inhibition of acetylcholine-induced contraction of the bladder body (1 x 10(-7) M to 1 x 10(-5) M) and the bladder base (1 x 10(-6) M, 1 X 10(-5) M) and was less potent than atropine and propantheline. In the rabbit significant blockade of acetylcholine-induced contractions occurred at dicyclomine concentrations of 5 x 10(-6) M to 3 x 10(-5) M in the bladder body and at 1 x 10(-5) M and 3 x 10(-5) M in the bladder base. In both species dicyclomine inhibitory effects were most marked in the bladder body, moderate in the bladder base, and minimal in the proximal urethra. Dicyclomine failed to cause inhibition of the barium chloride-induced contractions in the guinea pig vesicourethral smooth muscle. In rabbits, however, significant antagonism P less than 0.01) of barium chloride-induced muscle contraction was observed with dicyclomine at concentration 1 x 10(-5) M in both bladder body and the bladder base. The clinical implication of such properties of dicyclomine are discussed.