Methotrexate, vinblastine, doxorubicin and cisplatin followed by radiotherapy or surgery for muscle invasive bladder cancer: the University of Chicago experience.

A total of 29 patients with muscle invasive bladder cancer, clinical stage T2N0 (12), T3aN0 (9), T3bN0 (5), T3N2 (2) or T4N2 (1), underwent 2 to 4 cycles of neoadjuvant methotrexate, vinblastine, doxorubicin and cisplatin (M-VAC) chemotherapy followed by either radiotherapy (15), radical cystectomy (11) or no local therapy (3). The overall response rate to M-VAC chemotherapy was 69%, with 31% clinical complete responses and 38% clinical partial responses. A functioning bladder was maintained in 55% of the responding patients, although bladder wall calcifications were observed in 4 of 15 irradiated patients. Overall survival was 71% and disease-free survival was 55% at a median followup of 57 months. For the 12 stage T2N0 cancer patients overall survival was 100% at a median followup of 52 months. For the stages T3a and T3bN0 cancer patients overall survival was 63%, while all 3 node positive patients died. Neoadjuvant chemotherapy with a modified M-VAC regimen is well tolerated and may result in bladder preservation.

Female urinary tract fistulas.

Urinary tract fistulas in women are an uncommon complication of a variety of surgical procedures. However, such fistulas lead to significant patient and physician distress, and have important medicolegal implications. Successful repair of urinary tract fistulas requires careful preoperative evaluation and adherence to basic surgical principles. A variety of approaches and techniques may be used, and the choice of procedure is less important than achieving adequate resection of fibrosis with watertight, tension-free closure of well vascularized tissues in layers. Interposition grafts of omentum, muscle, peritoneum and labial fat may be used in recurrent, complicated or radiated fistulas, and add significantly to the rate of success. Overall, successful repair of urinary tract fistulas can be achieved in the majority of cases.

Curative radiotherapy following chemotherapy for invasive bladder carcinoma (a preliminary report).

Twenty-five patients with invasive transitional cell carcinoma of the bladder (Stage T2, T3, T4) received combined modality therapy using four cycles of methotrexate, vinblastine, adriamycin, and cisplatin (MVAC) chemotherapy followed by surgery or radiation therapy (RT). Sixteen patients had complete (N = 8) or partial (N = 8) response to MVAC. Curative RT was delivered to 11 responders with T2 or T3 disease and to 2 patients with T4 disease. All 11 with T2 and T3 disease are currently alive, 7 with normal bladder function. The two with T4 disease are dead of disease. Three patients required salvage cystectomy for local recurrence and one patient had cystectomy for bladder stones. Follow-up ranged from 11 to 50 months with a median of 31 months. No late chemo-radiotherapy treatment-related complications to the intestines or in bladder function (other than one bladder stone formation) occurred. These preliminary results are encouraging and warrant further evaluation of this innovative approach in treating invasive carcinoma of the bladder. T2 and T3 patients with a complete or partial response to MVAC may be excellent candidates for a bladder-sparing treatment.

Assessment of screening for prostate cancer using the digital rectal examination.

An early detection study for prostate cancer was initiated to determine the effect of routine digital rectal examinations on the stage of prostate cancer at diagnosis. A prostate biopsy was recommended if induration, asymmetry or nodules were detected on the digital examination. During a 6-year period 4,160 examinations were performed on 2,131 men more than 45 years old. A prostate biopsy was performed on 144 men and 36 malignant tumors were detected, of which 68 per cent were clinically localized. Pelvic lymph node metastases were found in 6 per cent of the surgically staged cancer patients and in 10 per cent of the patients who had a high grade tumor. Surgical staging revealed that 50 per cent of the patients with clinical stage B disease were upstaged to stage C or D1 disease. These results suggest that mass screening programs using digital examination may not add sufficient benefit over conventional medical care to warrant the expense. Definitive proof that screening can lower the mortality rate from prostate cancer can be obtained only by a prospective randomized clinical trial.

Progress and problems in screening for carcinoma of the prostate.

Carcinoma of the prostate is the second most common cause of cancer-related deaths in American men. This is due, in part, to the low percentage of cases that are diagnosed when the tumor is still curable. To improve early detection, routine screening has been performed using one or a combination of tests that included open prostate biopsy, serum acid phosphatase, the digital rectal exam, and transrectal sonography. These studies have been critically reviewed and the problems associated with prostate cancer screening have been discussed. No study has proven that routine screening reduces the mortality from prostate cancer. Furthermore, the positive predictive value and the sensitivity of each of these tests are too low for any of them to be useful for screening at the present time. To determine the value of screening, new studies are needed which should include a control group and an assessment of the disadvantages of screening as well as the potential benefits. Based on published reports, however, routine screening for prostate cancer using any test should be considered investigational at the present time.

Transrectal aspiration biopsy of the prostate: the importance of atypia.

Transrectal aspiration biopsy is useful as an alternative method to examine the prostate. As a means to improve the sensitivity of this method we investigated the significance of cellular atypia. Transrectal aspiration biopsy revealed highly atypical cells in 30 of 225 patients and in 17 patients slightly atypical cells were found. Biopsy was repeated in 22 patients with highly atypical cells and cancer was confirmed in 17 (77 per cent). In the group with only slight atypia 2 of 6 patients had cancer upon repeat prostatic biopsy. When transrectal aspiration biopsy contains highly atypical cells biopsy should be repeated to avoid a false negative diagnosis. These results suggest that atypia is an abnormal finding that must be followed clearly to maintain a high sensitivity with this biopsy method.

Influence of long-term aldose reductase inhibitor therapy on autonomic dysfunction of urinary bladder, stomach and cardiovascular systems in diabetic patients.

The effects of the aldose reductase inhibitor (ARI) sorbinil (250 mg/day) were tested in an open-label pilot study over 1 year, in eight diabetics with peripheral neuropathy, seven of whom had symptomic autonomic neuropathy (AN). Autonomic function studies of the urinary bladder, stomach and cardiovascular system were performed at baseline, 6 and 12 months. Six patients reported improvement in symptoms of AN by 6 months which was maintained or further improved by 12 months. Bladder sensation, as measured by cystometrographic parameters, improved at 6 months (P less than 0.02- less than 0.04), but by 12 months had reverted to baseline. Residual urine volume decreased at 6 months (P less than 0.06) and 12 months (P less than 0.06). Vagally mediated gastric acid secretion improved at 6 months (P less than 0.06); the subgroup of patients with subnormal secretion showed improvement to the normal range at 6 months (P less than 0.03). Gastric emptying of solid food was normal in six of eight subjects and showed no significant change at 6 months. Both patients with delayed emptying normalized. No change in beat-to-beat variability in heart rate with respiration was noted. Resting minimum heart rate decreased at 12 months (P less than 0.05). Glycohemoglobin levels showed no statistically significant changes. No toxic reactions were observed. These data suggest a beneficial effect of ARI treatment on symptomatic and asymptomatic manifestations of diabetic autonomic neuropathy and indicate a need for large controlled trials.

Use of sexual history to differentiate organic from psychogenic impotence.

The use of sexual symptomatology to differentiate psychogenic from organogenic impotence was studied. All patients were independently classified based on the evaluation of a minimum of one night of nocturnal penile tumescence recording, a sleep lab technician's rating of penile turgidity of erections, Doppler determination of penile blood flow, determination of serum prolactin and testosterone levels. Three aspects of symptomatology significantly discriminated the criterion groups. The single best predictor was the presence or absence of early morning erections as reported by the patient.

Psychiatric treatment of erectile dysfunction in urology outpatient clinic.

This study examined the feasibility of establishing a satellite psychiatry service in a urology outpatient clinic for the express purpose of engaging men with inhibited sexual excitement in psychiatric treatment. This approach appeared to be more successful as judged by complete referrals and symptom remission than referral to a psychiatry clinic.

The role of transrectal aspiration biopsy in the diagnosis of prostatic cancer.

We reviewed our experience with transrectal aspiration biopsy during an 18-month period. This procedure was the sole technique used in 75 men and prostatic cancer was diagnosed in 19. Two of these patients were not treated because a core biopsy performed at another hospital was negative for carcinoma. Aspiration and transperineal core biopsies were performed in 62 other cases. The sensitivity of aspiration to diagnose prostatic cancer was 98 per cent (45 of 46 biopsies) compared to only 81 per cent (37 of 46) for the core biopsy method. No patient suffered a complication following the aspiration biopsy. These data further support the value of transrectal aspiration biopsy as a sensitive, easy to perform method for sampling an abnormal prostate. More widespread use of this technique in the United States should be encouraged.

Comparison of the incidence of bladder hyperreflexia in patients with benign prostatic hypertrophy and age-matched female controls.

Detrusor hyperreflexia long has been recognized as a condition associated with certain neurological disorders (that is multiple sclerosis, cerebrovascular accidents, spinal cord injuries and parkinsonism). Bladder outlet obstruction (primarily benign prostatic hypertrophy) recently has been added to the list. Hyperreflexia associated with bladder outlet obstruction does not always resolve with relief of the obstruction. Our study of age-matched female controls indicates that there is a baseline rate of hyperreflexia associated with the aging process alone. This baseline hyperreflexia probably explains persistent symptoms in men with hyperreflexia following relief of the obstruction.

Early detection of prostate cancer by routine screening.

In an attempt to detect prostate cancer when the disease was still localized, a free screening clinic was established for men over the age of 45 years. Digital rectal examinations were performed for 811 men. Prostate biopsy was recommended to 43 in whom abnormalities were found by digital rectal examination; only 38 complied. Prostate cancer was detected in 11 men. The patients with cancer ranged in age from 60 to 79 years, with the highest incidence of cancer in the group aged 70 to 79 years. The overall incidence in men between 51 and 80 years old was 1.7%. Staging evaluation revealed that none of the patients with prostate cancer had metastases to the bone or elevated serum acid phosphatase levels. Five men (45%) were found by clinical or pathological methods to have stage B disease. Two others (18%) showed radiographic evidence of lymph node metastases (stage D1). The cost of detecting each cancerous prostate tumor was approximately +6,300. Routine screening can be a cost-effective method for diagnosing prostate cancer in patients with less extensive disease. The ability of early detection to prolong survival of patients with this disease will require further investigation.

Selective surface staining of bladder tumors by intravesical methylene blue with enhanced endoscopic identification.

Intravesical instillation of methylene blue resulted in selective surface staining of bladder tumors in vivo without staining the background of normal urothelium. Staining of human bladder tumors in vivo was accomplished by the intravesical instillation of 0.1% methylene blue in 0.9% saline through a foley catheter under 20 cm of hydrostatic pressure up to a maximum volume of 400 ml. After 5 minutes contact time, the methylene blue solution was drained, and the bladder was washed with saline. Thereafter, either endoscopic or open surgery was performed. The transitional cell carcinomas in 45 of 48 patients bound methylene blue to the surfaces of the tumors but not to normal urothelium. Higher grade tumors usually bound the dye more extensively than lower grades. The three patients, whose tumors did not bind methylene blue, had received previous chemotherapy, which might account for their being falsely negative. Carcinoma in situ and dysplasia did stain blue. Areas of hyperplasia and cystitis, however, did not bind methylene blue. In vivo intravesical staining with methylene blue has been a simple and safe procedure which has enhanced the endoscopic localization for biopsy and fulguration/resection of transitional cell carcinomas.

Intraoperative real time ultrasonic scanning for locating and recovering renal calculi.

Intraoperative ultrasonic guidance is a useful method to locate and to remove small renal stones broken from a larger stone during extraction, stones and calices proximal to a narrowed infundibulum and parenchymal calculi that should be removed during other procedures on the kidney.

Bladder and sexual dysfunction in multiple sclerosis.

Bladder dysfunction becomes manifest in various ways, and many therapeutic measures may be of value. Organic and psychiatric therapeutic techniques may be used in a sensitive and open approach to sexual dysfunction.