Study of cavernosal arterial anatomy using color and power Doppler sonography: impact on hemodynamic parameter measurement.

PURPOSE: We report on color and power Doppler ultrasound to study cavernosal arterial anatomy, and evaluate the impact of vascular anatomy on the measurement of hemodynamic parameters. MATERIALS AND METHODS: Cavernosal arterial anatomy of 42 patients with erectile dysfunction was evaluated using color and power Doppler ultrasound. A computerized waveform analysis was used to measure peak systolic velocity, end diastolic velocity and resistive indexes at various sites, including the penile crura, and proximal mid and distal penile shaft. Hemodynamic parameters were measured in each artery in cases of bifurcated or multiple cavernosal arteries. RESULTS: A total of 80 corpora were adequately evaluated. We observed a single artery without major proximal branches in 37 corpora, a single artery with major proximal branches in 17, bifurcated arteries in 15, 2 cavernosal arteries in 4 and marked arterial tortuosity in 1. In 6 corpora the main cavernosal artery arose from the superficial dorsal artery. The peak systolic velocity was highest at the proximal and decreased progressively at the distal site. The peak systolic velocity plus or minus standard deviation at the mid shaft averaged 69.3+/-30.0% of that at the proximal penile shaft. Of the 15 corpora with bifurcated arteries 67% had a 40% or greater difference in peak systolic velocity between the branches. Complete or partial occlusion of the cavernosal artery was identified in 3 corpora, and a dramatic difference in peak systolic velocity proximal and distal to the stenotic area was demonstrated. CONCLUSIONS: Cavernosal arterial anatomy is variable and hemodynamic parameters differ at various sites of measurement. Parameters should be measured at a consistent proximal site to obtain a reliable assessment. Variations in vascular anatomy and cavernosal artery pathology should be considered when interpreting color Doppler sonography and before penile vascular surgery.

Tumor localization and systemic absorption of intravesical instillation of radio-iodinated iododeoxyuridine in patients with bladder cancer.

PURPOSE: We evaluated tumor uptake and systemic distribution of intravesically instilled iododeoxyuridine (IUdR) in patients with superficial bladder cancer. MATERIALS AND METHODS: We performed 24 intravesical instillation studies in 11 patients with a mean age of 71 years. Radio-iodinated IUdR was administered through a Foley catheter. Gamma camera imaging was done after instillation and after 5 to 7 bladder irrigations. Tumor uptake was estimated by region of interest analysis. Bladder biopsy samples and surgical tumor specimens were tested for acid insoluble (deoxyribonucleic acid incorporated) radioactivity. Blood samples were obtained and analyzed for systemic absorption. RESULTS: Imaging was positive in all patients with bladder cancer. Average tumor uptake plus or minus standard deviation was 0.185+/-0.120% of the instilled dose. Preferential uptake of IUdR in the tumor was observed in all 6 patients undergoing tissue analysis. The tumor-to-normal bladder ratio ranged from 3.2 to 74,000 (median 202). Systemic absorption of IUdR was minimal. Blood sample analysis performed after intravesical instillation in all 11 cases revealed an average uptake of 3.2x10(-5)% instilled dose per ml. (range 0.69x10(-5) to 6.7x10(-5)) in the systemic circulation. Instillation within 24 hours after transurethral bladder tumor resection in 5 cases resulted in a higher but not dangerous average systemic uptake of 7.3x10(-4)% instilled dose per ml. (range 1.3x10(-5) to 2.6x10(-3)). Instillation 1 to 4 weeks after transurethral surgery in 8 cases resulted in no increased systemic absorption with an average blood level of 3.4+/-1.8x10(-5)% instilled dose per ml. There was no detectable distribution of radioactivity into other organs, including the thyroid. We noted no evidence of systemic toxicity in the study. CONCLUSIONS: Intravesical instillation of radio-iodinated IUdR achieves selective localization in the bladder tumor with minimal uptake by the normal bladder and minimal systemic absorption. The use of intravesical IUdR therapy for bladder cancer appears to be promising and requires further study.

Long-term outcome of prostatic stent treatment for benign prostatic hyperplasia.

OBJECTIVES: To evaluate the long-term result of prostatic stent treatment for patients with benign prostatic hyperplasia (BPH). METHODS: We reviewed our experience with prostatic stents in 24 patients with bladder outlet obstruction caused by BPH for whom up to 63 months of follow-up data were available. RESULTS: Prostatic stents were successfully placed in 24 of 25 patients enrolled in the study. All 9 patients treated for urinary retention voided spontaneously after stent placement. In 14 (93%) of 15 patients with nonretention, voiding symptoms decreased by 50% or more. The stent was removed in 9 patients for persistence of symptoms, symptom recurrence, or stent migration. Nine patients died of unrelated causes during the follow-up period. The stents functioned adequately in these patients until death. In the remaining 6 patients, the stent was still in place at the last follow-up visit (range 12 to 52 months, average 35) after placement, and their Madsen-Iversen symptom scores ranged from 3 to 10. Fourteen patients underwent cystoscopy 1 to 37 months after stent placement. Epithelium did not completely cover the stent in any of these patients; however, no stone formation was noted. CONCLUSIONS: Prostatic stents can be effective in relieving bladder outlet obstruction caused by BPH. They appear to be most useful in patients at high surgical risk and with a limited life expectancy. However, stent removal, which can be difficult, may be required in more than one-third of patients. We recommend prostatic stent placement primarily in patients who would otherwise be relegated to an indwelling catheter.

Radiolabeled iododeoxyuridine: safety evaluation.

UNLABELLED: The emphasis of radiolabeled iododeoxyuridine (*IUdR) research at our institution to date has been to assess its safety as a potential therapeutic agent. Toward this goal, we have performed preclinical and clinical studies, using various routes of administration, to detect adverse changes in normal tissues in both humans and animals. As IUdR is rapidly dehalogenated by the liver, the intravenous route is unlikely to be successful in therapeutic efforts. We have therefore focused our attention on more "protected" routes: intra-arterial and intravesicular administration. METHODS: Studies were performed in farm pigs after multiple administrations of [125I]IUdR into the aorta, carotid artery and bladder. IUdR and metabolites were measured in venous blood samples at appropriate time intervals after administration, after which histologic examination of tissues was performed. Studies in human have been performed after intra-arterial administration of [123I]IUdR in patients with liver metastases and intravesicular administration in patients with bladder carcinoma, initially using [123I]IUdR and currently using both [123I]IUdR and [125I]IUdR. Blood samples for pharmacokinetics and metabolite analysis and tissue for autoradiography (when feasible) have been obtained. RESULTS: To date, no evidence of adverse effects on normal tissue or alteration of hematologic or metabolic indices have been seen in pigs or humans. When instilled in the bladder, there is little leakage of IUdR in the circulation. CONCLUSION: When [125I]IUdR is used as a therapeutic agent, we anticipate little or no effect on normal tissues.

Treatment of recurrent vesicourethral anastomotic stricture after radical prostatectomy with endourethroplasty.

We report our experience with successful treatment of 2 cases of severe recurrent vesicourethral anastomotic stricture after radical prostatectomy with endourethroplasty. Both patients had multiple failures of conventional treatments but have been free of stricture recurrence after endourethroplasty with 11 and 25 months follow-up, respectively. Follow-up urethroscopy showed open anastomotic segments with epithelialization after endourethroplasty in both patients. The patient who was continent prior to endourethroplasty remained continent afterward.

Evaluation of urethral strictures and associated abnormalities using high-resolution and color Doppler ultrasound.

OBJECTIVES: To study the role of urethral sonography and color Doppler imaging in the evaluation of patients with urethral strictures and associated abnormalities. METHODS: We reviewed our experience with 41 urethral sonographic studies in 35 patients and compared them to 33 retrograde urethrograms. For 6 recent cases, we also used color Doppler imaging to assess spongiosal tissue blood flow and the location of urethral arteries. RESULTS: Both retrograde urethrography and urethral sonography assessed the caliber and length of the strictures well. Urethral sonography provided additional information about stricture involvement of the spongiosum, location of urethral arteries, and associated abnormalities (that is, periurethral abscess and urethrocutaneous fistula). This information was useful for the clinical stratification of urethral stricture disease and the planning of treatment. CONCLUSIONS: With the advantages of avoiding radiation to testis, providing real-time evaluation of the distensibility of the urethra, and having the capacity of assessing spongiosum and periurethral tissue involvement and urethral artery location, urethral sonography appears to offer more than retrograde urethrography for the evaluation of anterior urethral stricture.

Long-term experience utilizing a new balloon expandable prostatic endoprosthesis: the Titan stent. North American Titan Stent Study Group.

OBJECTIVES: To determine the long-term safety and efficacy of the Titan endoprosthesis as a therapeutic alternative in the management of men with bladder outlet obstruction. METHODS: One hundred forty-four patients (mean age, 73.5 years +/- 4.2) had placement of the Titan stent. The stents were inserted under direct vision and expanded to 33 F using a balloon catheter. Of the 144 patients, 59 (41%) were in urinary retention and 85 (59%) presented with moderate to severe symptoms of prostatism. Patients were assessed at baseline and in follow-up at 1, 3, 6, 12, 18, and 24 months. Parameters of evaluation included the Madsen-Iversen symptom questionnaire, peak flow rate (Qmax), postvoid residual urine volume (PVR), and incidence of adverse events. RESULTS: At 24 months, for the retention cohort, symptoms, Qmax, and PVR were 5.21 +/- 0.81, 11.34 +/- 1.12 mL/s, and 31.00 +/- 12.8 mL, respectively (P < 0.002). For patients with symptoms of bladder outlet obstruction, the results were as follows at 24 months: (1) symptoms decreased from 15.89 +/- 0.47 to 9.33 +/- 0.86 (P < 0.001); (2) Qmax increased from 8.59 +/- 0.41 mL/s to 11.43 +/- 1.12 mL/s (P < 0.001); and (3) PVR decreased from 116.94 +/- 19.95 mL to 74.4 +/- 36.2 mL (P < 0.03). There were minimal complications; stents were removed from 28 patients (19%) because of migration, 10 of which were placed by one investigator. CONCLUSIONS: When properly placed, the Titan stent was an effective therapeutic alternative to prostatectomy or long-term catheterization in high-risk obstructed patients or those in urinary retention.

Randomized comparison of balloon dilation and transurethral incision for treatment of symptomatic benign prostatic hyperplasia.

The concept of relieving the symptoms of benign prostatic hyperplasia (BPH) by dilating the urethral has existed for centuries. Thirty patients with a clinically estimated prostate gland size of 25 g or less were randomized to either balloon dilation (BDP) or transurethral incision of the prostate (TUIP). The mean pretreatment Madsen-Iverson symptom scores in the two groups were 15.0 +/- 4.9 (SD) and 15.4 +/- 4.4, respectively. The early response rates were 87% fo BDP and 86% for TUIP, with the mean symptom scores declining to 3.4 +/- 2.8 after dilation and 4.2 +/- 6.6 after incision. Among the 14 patients who initially responded to BDP, 2 have been lost to follow-up, 1 died of unrelated causes at 17 months with no urinary symptoms, 2 remain in response at 32 and 38 months, and the other 9 (75% of those available for evaluation) have developed recurrences. Among the 12 patents who responded to TUIP, 2 have been lost to follow-up, 8 remain in response at 14 to 48 months, and 2 (20%) developed recurrences by 44 months of follow-up. In the short term, both BDP and TUIP are effective for treating bladder outlet obstruction in men with relatively small prostates. However, the effect of dilation appears to be less durable than that of incision.

The titanium intraprostatic stent: the United States experience.

This multicenter, cooperative study represents the initial United States experience using an expandable, titanium intraprostatic stent in 68 patients (60 to 93 years old). The stents were inserted under direct vision and expanded to 33F using a balloon catheter. All patients had a symptom score analysis, and underwent measurement of peak urine flow and rate and post-void residual urine volume as part of the initial evaluation. Patients were seen at approximately 1, 3, 6 and 18 months after stent insertion (mean followup 16 months). Of the 68 patients 38 presented in urinary retention. The type of anesthesia used included general anesthesia in 6 patients, spinal or epidural anesthesia in 24, intravenous sedation in 20 and intraurethral lidocaine only in 18. All patients were able to void spontaneously within 36 hours after stent insertion. Symptom scores decreased from 16.8 to 3.9, 6.3, 5.0, 5.7 and 3.2 at approximately 1, 3, 6, 12 and 18 months, respectively. Peak urine flow rate increased from 3.9 to 13.8, 11.5, 11.2, 12.4 and 14.4 ml. per second at approximately 1, 3, 6, 12 and 18 months, respectively. Post-void residual urine volume decreased from 74.4 to 30.1, 29.2, 19.8 and 40.2 ml. at approximately 1, 3, 6 and 12 months, respectively. Of the initial 68 patients 5 died of the underlying disorder (all voiding satisfactorily with the stent in place) and 17 underwent uneventful stent removal (10 for technical failure and 7 for treatment failure). Technical failures were secondary to either inaccurate positioning or improper stent sizing. Of the 58 patients with proper placement of the stent and no technical failures 46 (79%) had improvement in symptom scores and urine flow rate. Transient hematuria was noted in 43 patients (63%) and usually resolved within 48 hours. None of the 6 urinary tract infections (9%) was recurrent. In conclusion, the titanium intraprostatic stent, when properly placed, is a promising therapeutic alternative to prostatectomy or long-term catheterization in high risk obstructed patients or those in urinary retention. Studies are currently in progress to determine the long-term efficacy of this therapeutic modality.

The impact of tumor size on the efficacy of monoclonal antibody-targeted radiotherapy: studies using a nude mouse model with human renal cell carcinoma xenografts.

Monoclonal antibody (Mab)-targeted radiotherapy is a unique approach in cancer therapy. Multiple factors affect the success of treatment. Internal radiation dosimetry and mini-dose Mab-targeted radiotherapy studies reveal that tumor size affects the efficacy of treatment. For tumors with calculated weight greater than 400 mg., intravenous administration of 131I-labeled A6H or A6H-C5H combination delivers significantly less tumor radiation dose (2070 +/- 580 cGy/100 microCi) than those for tumors of weight less than 200 mg. (5260 +/- 2460 cGy/100 microCi). In the mini-dose (an average of 73 to 86 microCi) Mab-targeted radiotherapy study of 109 mice with small tumors (six, 12, or 19 days after implantation), tumors 12 days after implantation (approximately 60 mg. in weight) showed regression in all mice and in 62% of mice gross tumor elimination was observed. In contrast, mini-dose therapy at day 19 (tumor weights approximately 170 mg.) resulted in tumor regression and tumor elimination rates of 33% and 17% respectively. These studies suggest that Mab-targeted radiotherapy is more suitable for treating small tumors.

Study of the clinical thermoluminescent dosimeter in the direct measurement of radiation adsorbed dose for radioimmunotherapy.

One of the major obstacles facing radioimmunotherapy (RIT) is the lack of a device to measure directly tumor and normal tissue radiation absorbed dose. Calculations based on the clearance and imaging scans have several limitations; hence we design and fabricate a sheathed clinical thermoluminescent dosimeter (TLD) for the measurement of absorbed dose by implantation in humans. Preclinical studies are performed in nine normal rabbits. Complete blood count, body temperature monitoring, clinical observation and necropsy show no untoward effects from the TLD. Consistent bone marrow radiation doses are noted in the four rabbits receiving 131I-labeled monoclonal antibody A6H. By using up to 20 clinical TLDs in one sheath, it will be possible to determine macroscopic heterogeneities in organs undergoing RIT.

Ureteral obstruction associated with prostate cancer: the outcome after percutaneous nephrostomy.

We retrospectively reviewed the outcome of 37 prostate cancer patients with ureteral obstruction treated by percutaneous nephrostomy. The over-all survival was 57% at 1 year and 29% at 2 years (median survival time 21 months). The 1 and 2-year survival rates of 15 patients with no prior hormonal therapy were 73 and 47%, respectively, while those of patients who had previously received hormonal therapy were 48 and 19%, respectively. Median survival times of these groups were 24 months and 12 months, respectively. Of 12 patients who had severe renal failure before percutaneous nephrostomy (serum creatinine greater than or equal to 6.9 mg. per dl.) 9 had an adequate return of renal function (serum creatinine less than 3 mg. per dl.) after drainage and 58% survived more than 1 year (median survival time 22 months). Percutaneous nephrostomy is safe and effective in relieving ureteral obstruction and reasonable survival can be achieved even in patients with renal failure. Percutaneous nephrostomy should be considered strongly in these patients.

Cosmetic orchiectomy for prostate cancer.

With several effective therapeutic methods available for achieving androgen ablation, we must respect the psychological needs of our patients. The choice should ultimately be made by the patient after a thoughtful discussion of the advantages and disadvantages of various approaches. Cosmetic orchiectomy has the advantages of having the minimal morbidity of a simple operation, achieving the reliable result of androgen ablation and preserving the physical male organ without the risk of drug side effects and the dependence on patient compliance. In our experience, the operation is satisfactory both in achieving the therapeutic goal of androgen deprivation and in meeting the psychological needs of patients.

Biodistribution and radioimmunoscintigraphy studies of renal cell carcinoma using tumor-preferential monoclonal antibodies and F(ab')2 fragments.

The in vivo localization of renal cell carcinoma-preferential monoclonal antibodies A6H, D5D, and C5H was evaluated and the biodistribution of F(ab')2 antibody fragments of A6H and the intact Mab were compared in over 100 nude mice. A6H localized well to most renal cell carcinoma xenografts studied; the median tumor to blood ratios ranged from 6.4 to 11.5 for various xenografts. C5H also localized well to most renal cell carcinoma xenografts tested. However, D5D did not localize well to renal cell carcinoma xenografts in vivo despite its highly restrictive in vitro reactivity. The F(ab')2 fragments of A6H produced higher tumor to blood ratios, which probably resulted from fast clearance of the fragments from the circulation. Preliminary results showed that indium-111 labeling may further improve imaging.

Adjunctive endourological technique for transurethral resection in patients with urethral stricture.

Attempts to dilate the urethra with metal sounds and to insert a resectoscope sheath with the metal obturator can be traumatizing in patients with urethral stricture or false passage. We describe a simple technique that uses endourological instruments to facilitate insertion of the resectoscope sheath and placement of the post-resection Foley catheter.

Endoscopic treatment of posterior urethral obliteration: long-term followup and comparison with transpubic urethroplasty.

We compare our results with the endoscopic management of posterior urethral obliteration in 8 patients to our previous experience with transpubic urethroplasty in 6 patients. Although most patients who underwent an endoscopic procedure required 2 or 3 followup internal urethrotomies within the first 2 to 10 months after treatment, 6 have remained free of stricture for more than 2 years after this initial period of aggressive endoscopic management. This finding suggests that total obliteration of the posterior urethra can be managed effectively by endoscopic techniques. Comparison of endoscopic treatment with transpubic urethroplasty revealed a decrease in operative time, blood loss and hospital stay with endoscopic management. We recommend that transpubic urethroplasty be reserved for patients in whom urethral continuity cannot be re-established with relatively safe and simple endourological techniques.

Endourethroplasty in the management of complicated posterior urethral strictures.

A 2-step endourethroplasty was performed to repair complicated posterior urethral strictures in 3 patients. In the first procedure scar tissue was resected transurethrally to create a smooth grafting bed. In a second endourological procedure a piece of full thickness prepuce was grafted at the stricture site. An intraluminal balloon catheter was used to keep the skin graft in close contact with the resected area of the urethra. Of the patients 2 have remained free of stricture for more than 22 months and 1 has remained free of stricture for more than 12 months after endourethroplasty. The technique offers a promising alternative to open surgery in selected patients with complicated posterior urethral strictures.