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It has long been recognized that interstitial cystitis (IC) is a disease of the urothelium. In this article, we review the results of published studies and present new data concerning the precise role of the bladder epithelium in IC. We discuss bladder defenses against both the penetration of urinary solutes and bacterial adherence, and we present new information about the proteoglycans that are present on the normal bladder. Previously published results and new data presented here support the conclusion that IC involves an aberrant differentiation program in the bladder urothelium that leads to altered synthesis of several proteoglycans, cell adhesion and tight junction proteins, and bacterial defense molecules such as GP51. These findings lend support to the rationale for glycosaminoglycan replacement therapy for the treatment of patients with IC.

The etiology of urinary tract infections (UTIs) that require hospitalization, whether they originate in the hospital or in the community, is changing, with increasing findings of gram-positive organisms. The Council for Appropriate and Rational Antibiotic Therapy (CARAT) criteria recommend evaluating treatment choices on the basis of sound clinical evidence, potential for therapeutic benefits, safety, optimal duration of treatment, and cost-efficacy in order to improve antibiotic treatment. Evidence-based guidelines recommend fluoroquinolones for the treatment of patients with cases of pyelonephritis or bacterial prostatitis severe enough to warrant hospitalization. For other serious UTIs, fluoroquinolones are usually recommended either when traditional agents have failed or when resistance to traditional agents is high. Even in the context of rapidly changing antimicrobial resistance patterns, the fluoroquinolones have maintained consistent, well-tolerated efficacy against many of the principal organisms responsible for UTIs, and are generally considered safe for most patients. To increase the likelihood of treatment success with first-line therapy, an antimicrobial agent must attain sufficient concentrations in the target tissue or in the urine for an appropriate amount of time. Both levofloxacin and gatifloxacin are excreted unchanged in the urine in concentrations that far exceed the minimum inhibitory concentration of most uropathogens. Factors that affect cost-effectiveness that should be considered include acquisition costs as well as treatment success and ease of use for hospital staff.

Purpose: Vaccinia virus is a DNA poxvirus previously used as a vaccine to eradicate smallpox. The virus has a high efficiency of infection, replicates in the cytoplasm without chromosomal integration and can transport a large amount of recombinant DNA without losing infectivity. Therefore, it is an excellent choice as a vector for gene delivery in vivo. Large quantities of vaccinia have been injected into dermal, subcutaneous and peripheral lymph node melanoma metastases without significant side effects, and with efficient infection of the tumor cells and recombinant gene transfection. To determine if vaccinia, when given intravesically, can effectively infect bladder mucosa and tumor with acceptable toxicity, we performed a phase I trial of intravesical vaccinia in patients with muscle invasive transitional cell carcinoma before radical cystectomy., Materials and Methods: After documenting immune competence and demonstration of a major reaction after revaccination, patients received 3 increasing doses of intravesical Dryvax vaccinia virus (Wyeth-Ayerst Laboratories, Philadelphia, Pennsylvania) that was provided by the Centers for Disease Control. Approximately 24 hours after the third dose, cystectomy was performed and the tissue was examined microscopically., Results: There were 4 patients who were treated. The 3 patients who received the highest doses (100 x 106 plaque forming units) had significant mucosal and submucosal inflammatory infiltration by lymphocytes, eosinophils, and plasma cells into tumor and normal tissue. Dendritic cells were recruited to the site after exposure to the vaccinia. Significant mucosal edema and vascular ectasia were seen. Tumor and normal urothelial cells showed evidence of viral infection, including enlarged vacuolated cells with cytoplasmic inclusions. There were no clinical or laboratory manifestations of vaccinia related toxicity except mild dysuria. Of the 4 patients 3 survived and were free of disease at 4-year followup., Conclusions: Our study demonstrates that vaccinia virus can be administered safely into the bladder with recruitment of lymphocytes and induction of a brisk local inflammatory response. To our knowledge, this is the first report of direct delivery of live virus into the human bladder. The role of wild type vaccinia as immunotherapy for bladder cancer warrants further study. Furthermore, these data support the exploration of recombinant vaccinia as a putative gene therapy vector for intravesical infection and transfection of bladder tumor cells with cytokine or other genes, an approach that our group pioneered and most recently studied in patients with superficial melanoma.

Purpose: We evaluated the effect of three-dimensional conformal radiation therapy (3D-CRT) with or without hormonal therapy (HT) on sexual function (SF) in prostate cancer patients whose SF was known before all treatment., Methods and Materials: Between March 1996 and March 1999, 144 patients received 3D-CRT (median dose = 70.2 Gy, range 66.6-79.2 Gy) for prostate cancer and had pre- and post-therapy SF data. All SF data were obtained with the O'Leary Brief SF Inventory, a self-administered, multidimensional, validated instrument. We defined total sexual potency as erections firm enough for penetration during intercourse. Mean follow-up time was 21 months (SD +/- 11 months). The Wilcoxon signed-rank test was used to test for significance of the change from baseline., Results: Before 3D-CRT, 87 (60%) of 144 men were totally potent as compared to only 47 (47%) of 101 at 1-year follow-up. Of the 60 men totally potent at baseline and followed for at least 1 year, 35 (58%) remained totally potent. These changes corresponded to a significant reduction in SF (p < 0.05). Patients who had 3D-CRT alone were more likely to be totally potent at 1 year than those receiving 3D-CRT with HT (56% vs. 31%, p = 0.012); however, they were also more likely to be potent at baseline (71% vs. 44%, p = 0.001). Although these two groups had a significant reduction in SF from baseline, their change was not significantly different from each other., Conclusion: These data indicate that 3D-CRT causes a significant reduction in total sexual potency as compared to pretreatment baseline. The addition of HT does not appear to increase the risk of sexual dysfunction.

Purpose: A major component of bladder surface mucin is a glycoprotein GP51 (molecular weight 51 kD.). GP51, which has previously been isolated from rabbit mucosa, appears to function as part of the defense mechanism in an in vivo infection model. GP51 coats the epithelium and is secreted into the urine, as detected by immunohistochemical testing and enzyme-linked immunosorbent assay (ELISA). Increased urinary GP51 occurs during urinary tract infection. To elucidate the role of GP51 as a component of the primary defense mechanism we studied interactions with uropathogenic bacterial isolates and urine from symptomatic patients with urinary tract infection., Materials and Methods: ELISA was performed to demonstrate the binding of GP51 and various uropathogens. Immunochemical studies were done using monoclonal antibodies to GP51 to determine the interaction of GP51 with certain uropathogenic isolates, including Escherichia coli, Enterobacter cloacae, Klebsiella pneumoniae, Proteus vulgaris, Pseudomonas aeruginosa, Serratia marcescens, Staphylococcus aureus, S. epidermidis and Streptococcus faecalis. Infected urinary sediments and uropathogenic bacterial cultures were examined by immunocytochemical testing to localize GP51. Antigen inhibition ELISA was done to quantitate urinary GP51 in the urine of 17 normal controls and 19 patients with urinary tract infection., Results: ELISA revealed that GP51 binds to a wide spectrum of gram-positive and gram-negative uropathogens in semiquantitative fashion. Immunochemical methods confirmed that purified GP51 binds to bacteria, encapsulating and aggregating the bacteria. Clinical specimens showed GP51 localized to bacteria and uroepithelial cells. We observed a significant increase in urinary GP51 in urinary tract infection compared to uninfected urine (p = 0.0003)., Conclusions: These studies suggest that GP51, a component of bladder mucin, may be a strategic factor in the primary defense mechanism of the bladder.

Purpose: Previous studies have indicated that high-energy transurethral microwave thermotherapy (TUMT) requires intravenous (IV) sedation and/or narcotics for patient tolerance. This study was performed to determine tolerability, patient acceptance, and efficacy of TUMT using both low- and high-energy protocols in a single United States university setting., Materials and Methods: Between August 11, 1997 and October 28, 1999, 210 men (mean age 64.9 +/- 9.1 years) presenting with symptomatic benign prostatic hyperplasia (BPH) received treatment with a Prostatron TUMT using either the low-energy Prostasoft 2.O or high-energy Prostasoft 2.5 software. Each patient had digital rectal examination and prostate-specific antigen level consistent with BPH, American Urological Association symptom score > or = 15, and Qmax <15 mL/s. Each patient received TUMT with only ibuprofen 400 mg by mouth (PO), lorazepam 1.0 mg PO, and ketorolac 30 mg intramuscularly (IM) prior to TUMT. A few patients who were concerned about limited pain threshold received oxycodone 5 mg/acetaminophen 325 mg PO. Of 210 patients treated, 12-month efficacy data were available for analysis in 80 patients., Results: Forty-eight men (mean age 65 +/- 9.2 years) received low-energy 2.0 software TUMT, and 32 men (mean age 65.1 +/- 9.2 years) were treated with high-energy 2.5 software. Mean prostatic volume was 44.3 +/- 23.9 mL and 60.7 +/- 26.4 mL for the 2.0 and 2.5 groups, respectively. Mean energy delivered was 108.8 +/- 50.4 kJ and 173.1 +/- 41.1 kJ for the 2.0 and 2.5 treatment groups, respectively. International Prostate Symptom Score decreased from 23 pre-TUMT to 8 post-TUMT and 21 pre-TUMT to 10 post-TUMT at 12 months in the 2.0 and 2.5 groups, respectively. Mean peak flow rate improved 31.9% from 9.1 mL/s pre-TUMT to 12.0 mL/s post-TUMT and 45.8% from 9.6 mL/s pre-TUMT to 14.0 mL/s post-TUMT at 12 months in the 2.0 and 2.5 groups, respectively. All but two patients tolerated treatment without IV sedation. One patient experienced intolerable rectal spasm, and treatment was terminated in another patient because of poorly controlled hypertension., Conclusions: Patients can be treated safely with TUMT using either low or high energy, with almost universal patient tolerance and without the need for IV sedation or narcotics, if they premedicated effectively using a PO/IM regimen. Patients experience significant relief of symptoms whether low- or high-energy TUMT is used; however, high-energy TUMT improves flow rate to a greater extent than does low-energy therapy.

The optimum management for an individual patient with prostate cancer is not well defined. Patients with localized disease may be offered options ranging from observation, hormonal therapy, cryotherapy, radiation therapy, or surgery. Each option may have unique aspects to consider when counseling a patient often leading to multiple physician visits over an extended period of time. Since 1996, the Kimmel Cancer Center of Thomas Jefferson University has offered newly diagnosed urologic cancer patients the opportunity to be evaluated in a multidisciplinary clinic. Here, multiple physician consultative visits, including pathologic and radiologic evaluation and protocol evaluation, are provided during the session. Herein we report on our experience with this multidisciplinary approach for patients with prostate cancer.

Indwelling urethral catheters are commonly used in patients admitted to acute care hospitals. Forty percent of nosocomial infections occur in the urinary tract, and greater than 80% of these infections are secondary to an indwelling urethral catheter. Fortunately, the majority of catheters are left indwelling for a short period of time. The duration of catheterization is directly related to the development of bacteriuria, nosocomial infection, and possible bacteremia with sepsis. A relatively low percentage of patients become infected during the first 3 to 5 days if sterile technique and proper maintenance of a closed system are performed. Bacteria may grow in the urine (planktonic) and ascend via the lumen, or bacteria in the biofilm around the outside of the catheter may infect the bladder. Most organisms are from the patient's intestinal flora, but exogenous sources on or near the patient may be involved. The major morbid events associated with the catheter are fever and the possible progression to bacteremia and sepsis. Early recognition of complications and arresting their progression, especially in the high-risk patient, are essential. Current research is directed at developing ways to reduce infection beyond the sterile closed system.

Purpose: This study examines the effect of adjuvant radiation therapy (RT) on outcome in patients with pT3N0 prostate cancer and makes comparisons to a matched control group., Methods and Materials: At our center, 149 patients undergoing radical prostatectomy were found to have pT3N0 prostate cancer, had an undetectable postoperative prostate-specific antigen (PSA) level, and had no immediate hormonal therapy. Fifty-two patients received adjuvant RT within 3 to 6 months of surgery. Ninety-seven underwent radical prostatectomy alone and were observed until PSA failure. From these two cohorts, we matched patients 1:1 according to preoperative PSA (<10 ng/ml vs. >10 ng/ml), Gleason score (<7 vs. > or =7), seminal vesicle invasion, and surgical margin status. Seventy-two patients (36 pairs) were included in the analysis. Median follow-up time was 41 months. We calculated a matched-pairs risk ratio for cumulative risk of PSA relapse (a rise above 0.2 ng/ml)., Results: After controlling for the prognostic factors by matching, there was an 88% reduction (95% confidence interval [CI]: 78-93%) in the risk of PSA relapse associated with adjuvant RT. The 5-year freedom from PSA relapse rate was 89% (95% CI: 76-100%) for patients receiving adjuvant RT as compared to 55% (95% CI: 34-79%) for those undergoing radical prostatectomy alone., Conclusions: These data suggest that adjuvant RT for pT3N0 prostate cancer may significantly reduce the risk of PSA failure as compared to radical prostatectomy alone. Its effect on clinical outcome awaits further follow-up.

Purpose: GP51 is a urinary glycoprotein with a molecular weight of 51 kDa. This glycoprotein is produced and secreted by the transitional epithelium of the genitourinary tract, and has been isolated from human urine. Studies have demonstrated that GP51 levels are decreased in bladder biopsies of patients with interstitial cystitis. We evaluated urinary GP51 in a noninvasive manner as a clinical marker of interstitial cystitis., Materials and Methods: Urinary GP51 levels were measured using antigen inhibition enzyme-linked immunosorbent assay. In blinded fashion we analyzed for quantitative differences 24-hour urine samples of 36 patients with interstitial cystitis and 23 normal controls who were age matched within 5 years (mean age 47.3). We also evaluated GP51 in random urine specimens of 17 normal controls, 14 patients with interstitial cystitis and 11 subjects who had undergone cystectomy to determine whether urinary GP51 is mainly produced by the bladder, which is the site of interstitial cystitis. To ascertain the specificity of urinary GP51 to interstitial cystitis urine samples of 34 patients with other urological diseases were measured and compared with findings in the samples of 15 with interstitial cystitis., Results: Low GP51 levels appeared to be unique to the interstitial cystitis state compared to normal (p = 0.008). GP51 in patients with interstitial cystitis and in those who underwent cystectomy was lower (p < 0.001) than in normal controls. These findings suggest that the major source of urinary GP51 is the bladder. Also, we observed lower GP51 levels in interstitial cystitis than in other urinary tract diseases (p < 0.0001)., Conclusions: Our study substantiates the possibility of using GP51 as a clinical marker for diagnosing interstitial cystitis by a noninvasive urinary assay.

Objectives: To determine the durable efficacy of early postoperative radiation therapy (RT) in patients with pT3N0 prostate cancer who were at an increased risk of biochemical failure. We also evaluated the long-term benefit derived from using higher RT doses., Methods: Seventy-nine patients with pathologic Stage T3N0 prostate cancer and high-risk postoperative features underwent RT within 6 months after surgery. No patient received prior hormonal therapy. Fifty-nine patients had positive surgical margin, 29 had pathologic seminal vesicle invasion, and 27 had persistently elevated postoperative prostate-specific antigen (PSA) levels. Freedom from biochemical relapse (bNED) was defined as an undetectable (less than 0.2 ng/mL) PSA level. Median follow-up time was 39 months, and the median radiation dose was 64.8 Gy. All patients were followed for at least 2 years to be considered biochemically controlled., Results: Patients receiving adjuvant RT for an undetectable pre-RT PSA level had a 3-year bNED rate of 90%, compared with 44% for those receiving salvage RT for a detectable level (P < 0.0001). In the group of adjuvant patients, RT doses more than 61.2 Gy resulted in a 3-year bNED rate of 90% compared with 64% for those receiving a lower dose (P=0.015). The salvage patients irradiated with a dose of 64.8 Gy or greater had a 3-year bNED rate of 52% compared with 18% for those irradiated with lower doses (P=0.048). Severe late RT-related complications were infrequent and did not correlate with dose., Conclusions: In patients with high-risk pT3N0 prostate cancer, an RT dose response may exist. Although some studies suggest limited durable efficacy for early postoperative RT, our data suggest that RT doses of 64.8 Gy or more appear superior to prevent future biochemical failures. A prospective randomized study evaluating a postoperative RT dose response is warranted.

Purpose: The appropriate radiation dose has not been determined for postoperative radiation therapy (RT) of prostate cancer. Postoperative PSA level is a useful marker of local residual disease, and may allow evaluation of RT dose-response after radical prostatectomy., Methods and Materials: Between 1989 and 1996, 86 consecutive patients with pT3N0 prostate cancer who did not receive prior hormonal therapy or chemotherapy were irradiated postoperatively. All patients received 55.8 to 70.2 Gy (median = 64.8 Gy) to the prostatic/seminal vesicle bed. Patients were judged to be free of biochemical failure (bNED) if their PSA remained undetectable or decreased to undetectable level (< 0.2 ng/ml). The median follow-up time was 32 months from time of irradiation., Results: Univariate and multivariate analyses of variables showed that the preRT PSA level was the most significant predictor of improved bNED survival (p < 0.001). Actuarial analyses of radiation dose grouped with preRT PSA levels found higher radiation dose to be significant (p < 0.05). For the 52 patients with an undetectable preRT PSA level, the 3-year bNED rate was 91% for patients irradiated to 61.5 Gy or more and 57% for those irradiated to lower doses (p = 0.01). For the 21 patients with preRT PSA level > 0.2 and < or = 2.0 ng/ml, the 3-year bNED rate was 79% for patients irradiated to 64.8 Gy or more and 33% for those irradiated to a lower dose (p = 0.02). No other preRT PSA interval or radiation dose level was associated with a dose-response function., Conclusion: In patients with pT3N0 prostate cancer after radical prostatectomy, a radiation dose-response function may be present and depends on the preRT PSA value. Patients with high postoperative PSA levels (> 2.0 ng/ml) may be less likely to benefit from higher doses of RT, and should be considered a group for which systemic therapy should be tested.

We investigated the utilization patterns of autologous blood donation for radical retropubic prostatectomy (RRP) during a 6-year period. A total of 225 patients electing RRP with blood donation were identified for analysis. Group 1 consisted of 113 men who had an RRP from 1990 to 1993. Group 2 consisted of 112 men who had an RRP from 1993 to 1995. Charts were reviewed for the number of units transfused, number of autologous units donated, and operative blood loss. More patients autodonated blood in the later group (84% vs. 75%). Technical improvements and experience have significantly decreased blood loss and the need for transfusions (69% vs. 96% in the early group). In the more current series, only 14% of patients who autodonated blood required homologous transfusion vs. 42% in the earlier group. An increase in the amount of wasted blood (42% vs. 16% in the early group) also was noted. The 4-unit donors had the lowest homologous transfusion rate in both series (group 1 = 21%, group 2 = 5%); the 2-unit donors had the lowest units wasted per person (0.74). In addition, the 2-unit donors maintained a low homologous transfusion rate of 16%. These data suggest that 2 units of autologous blood donation has a reduced risk of homologous blood transfusion while the amount of autologous blood wasted is minimized.

Objectives: At our institution, a Phase II trial using androgen suppression followed by surgery was completed for men with Stage T3 disease and negative laparoscopic nodal dissection. We recently reported the unfavorable biochemical outcome of that experience. Because that analysis did not include a control group of irradiated patients, the current project was undertaken to compare that Phase II experience with clinical Stage T3 patients treated at our institution with definitive irradiation during an overlapping period of time., Methods: The Phase II trial included 21 patients with T3 tumors and negative laparoscopic nodal dissections treated by 4 months of neoadjuvant hormonal treatment (leuprolide +/- flutamide) prior to radical prostatectomy. Patients who declined to participate in the study or those judged ineligible by virtue of poor surgical risk were treated with definitive irradiation (n = 29). Although the radiation portals were shaped with multileaf collimation, no attempt was made to design "conformal fields." The median dose was 68 Gy (range 66 to 72) delivered in conventional fractionation. Biochemical failure after prostatectomy was defined as prostate-specific antigen (PSA) levels exceeding 0.2 ng/mL. Biochemical failure after irradiation was defined as a rise in absolute level of PSA greater than 1.5 ng/mL, or two consecutive elevations of PSA on sequential measurements, even if the absolute level was less than 1.5 ng/mL., Results: In univariate comparison, the freedom from biochemical relapse rate at 3 years was 41% for irradiated patients and 23% for those treated by hormones combined with surgery (P <0.05). In a multivariate regression model controlling for the prognostic factors of baseline PSA, age, clinical substage, Gleason score, and treatment modality (induction androgen suppression + prostatectomy versus radiotherapy), only low baseline PSA independently predicted improved freedom from biochemical recurrence (P = 0.04)., Conclusions: The combination of induction hormonal treatment followed by radical prostatectomy offered no advantage over irradiation alone in this single institutional experience. Notwithstanding, the majority of men treated by definitive radiotherapy manifested biochemical failure. More innovative strategies such as conformal irradiation (either alone or combined with androgen ablation) and radiation dose escalation should be pursued to optimize outcome for this unfavorable group of patients.

The uroflowmeter is perhaps the most important and certainly the most commonly used urodynamic instrument currently employed in urologic practice. The modern uroflowmeter was invented by Willard M. Drake, Jr., in 1946 at the Jefferson Medical College. The original manuscript, entitled "The uroflometer: an aid to the study of the lower urinary tract," appeared in Journal of Urology in 1948. Drake obtained a US patent for the device, entitled "Uroflometer," in 1953. The flowmeter, originally manufactured by van Beek Industries, was more recently manufactured and distributed by Grewe Plastics. Drake is now retired and living in Nacogdoches, Texas.

Background and Objectives: We retrospectively examined the effects of epidural analgesia on patients undergoing radical retropubic prostatectomy (RRP)., Methods: Patients (203) underwent radical retropubic prostatectomy under either general or epidural anesthesia alone or a combined general epidural technique. Of those, 143 had an epidural catheter placed and underwent radical retropubic prostatectomy under general anesthesia followed by postoperative epidural analgesia (Group E+G). Twenty-eight patients had the operation under epidural anesthesia followed by epidural analgesia in the postoperative period (Group E). Thirty-two patients had general anesthesia for the operation and postoperative systemic analgesia (Group G)., Results: There were no significant differences between the groups with respect to age, height, weight, ASA status, or operation time. The length of postoperative hospital stay was significantly longer in the general anesthesia group patients as compared to the other two groups (P < 0.05). Intraoperative blood loss and blood replacement were significantly higher in the general anesthesia group (P < 0.001). There were no significant differences between the groups with respect to return of bowel function postoperatively, or incidence of complications., Conclusions: Epidural anesthesia and analgesia following radical retropubic prostatectomy have demonstrated a number of beneficial effects. These include decreased blood loss and shorter hospital stay.

Objectives: There is interest in treating prostate cancer with induction androgen deprivation prior to radical prostatectomy. Data on long-term prostate-specific antigen (PSA)-based survival analyses among patients treated with neoadjuvant hormonal therapy (NHT) and prostatectomy are limited. In 1991 we instituted a pilot study for T3 disease based on endorectal coil magnetic resonance imaging (eMRI), mandatory negative laparoscopic nodal dissection prior to hormonal manipulation, and prostatectomy followed by pathologic and PSA-based outcome determinations., Methods: Of 26 patients, 21 had negative laparoscopic lymphadenectomy followed by 4 months of NHT (leuprolide +/- flutamide) prior to radical prostatectomy. eMRI was performed at the time of diagnosis and following hormonal treatment. Serum PSA was determined at 3-month intervals. Prostatectomy specimens were evaluated by 3-mm whole-mount step sections., Results: Prior to prostatectomy, biochemical response was documented in all patients and downsizing was observed by eMRI in 57%. Pathologic downstaging to a lower stage (T2c or lower) was achieved in 48%. However, the actuarial 3-year freedom from biochemical relapse rate was only 24%., Conclusions: Using laparoscopy to exclude node-positive patients and 4 months of NHT appears to result in pathologic and initial biochemical evidence of regression. These factors have not translated into improved freedom from biochemical relapse among patients with Stage T3 disease treated with NHT and prostatectomy. Recent data strongly suggest a beneficial effect in patients with clinical T2 disease treated with NHT and radical prostatectomy. The NGT and radical prostatectomy approach appeared to offer no clear advantage when compared with PSA-based benchmarks achieved with conformal irradiation or NHT followed by external beam treatment among patients with clinical T3 disease.

It has previously been demonstrated that the urinary tract contains a unique glycoprotein (GP1) that appears to serve a function in the clearance of pathogenic bacteria. We prepared a panel of monoclonal antibodies (mAbs) to human GP1 and examined its antigenic specificity and distribution in the human urinary tract. This was also observed in relation to another glycoprotein associated with infection, Tamm-Horsfall protein (THP), as well as to URO-5, a protein used in identifying the lower urinary tract. In enzyme-linked immunoadsorbent assays (ELISA), all of the GP1 mAbs reacted with GP1 prepared from both human urine and rabbit bladder mucosa. No immunoreactivity was observed with either THP mAbs or URO-5 mAbs. Western-blot analyses using GP1 mAbs with human urine GP1 preparations detected a single band of approximately 50-52 kDa. Human urinary tract tissues were also examined by immunohistochemical techniques using the GP1 mAbs, commercial THP, and URO-5 mAbs. In paraffin-embedded bladder sections, only GP1 mAbs reacted with the urothelium. Selective staining of distal collecting tubules, renal pelvis, and ureters was demonstrated for GP1 mAbs. Proximal convoluted tubules, loops of Henle, and Bowman's capsule failed to stain for GP1. In the same tissues, THP mAbs reacted with the thick and thin segments of medullary loops of nephrons (Henle's loops). URO-5 mAbs stained fresh frozen sections of bladder urothelium, distal collecting tubules, and portions of Henle's loops; however, they failed to stain paraffin-embedded tissue sections. These GP1 mAbs provide a new tool for biochemical and histochemical investigations of the mucin layer in both healthy and diseased urinary tract tissue.

Intermittent pneumatic compression devices are a widely used, effective and presumed risk-free method of deep venous thrombosis prophylaxis, presumably by increasing peak venous blood velocity, and stimulating local and systemic fibrinolysis. We investigated whether intermittent pneumatic compression devices had any effect on intraoperative blood loss or transfusion during radical pelvic urological surgery. To our knowledge no previous study has addressed these issues. Records were reviewed for patients undergoing radical retropubic prostatectomy or radical cystectomy with diversion from 1985 to 1990. A total of 91 cases was reviewed: 38 radical retropubic prostatectomies and 53 radical cystectomies with diversion (34 male and 19 female patients). There were 59 patients with intermittent pneumatic compression devices (29 radical retropubic prostatectomies and 30 radical cystectomies with diversion) and 32 without intermittent pneumatic compression devices (9 radical retropubic prostatectomies and 23 radical cystectomies with diversion). Intraoperative blood loss and transfusions were calculated for each group with and without intermittent pneumatic compression devices. No clinically apparent lower extremity deep venous thrombosis or pulmonary embolus was diagnosed in any patient. For the group with intermittent pneumatic compression devices mean intraoperative blood loss was 2,541 ml. (range 700 to 8,850) versus 1,807 ml. (range 450 to 5,100) without a device, for a statistically significant difference of 734 ml. (p = 0.005). When 5 patients with excessive intraoperative blood loss (more than 5,000 ml.) were excluded the statistically significant difference was maintained. When comparing radical retropubic prostatectomy and radical cystectomy with diversion, with and without intermittent pneumatic compression devices, blood loss was greater for the group with a device for each procedure. Differences in intraoperative blood loss were independent of sex or tumor stage. Intraoperative transfusions were increased by approximately 0.6 units per patient with the device. Our study suggests that intermittent pneumatic compression devices may increase blood loss during a radical pelvic operation.

Metastatic involvement of pelvic lymph nodes in carcinoma of the prostate alters the prognosis and treatment of this disease. Our goal was to determine if additional techniques, such as immunohistochemical staining, could detect occult microscopic metastatic nodal disease not seen with routine hematoxylin and eosin staining. We examined paraffin embedded lymph nodes from 43 patients with clinical stage A or B carcinoma of the prostate who were candidates for radical prostatectomy and who underwent modified pelvic lymph node dissection with frozen section hematoxylin and eosin staining. Immunohistochemical staining for prostate specific antigen and prostate specific acid phosphatase was performed on the lymph nodes. Monoclonal antibodies to cytokeratins were used to confirm the epithelial origin of the prostate cells. An average of 9 lymph nodes and 42 histological sections per patient were stained. Based on routine hematoxylin and eosin staining the pathological staging was stage A in 3, stage B in 20, stage C in 9 and stage D1 in 11 cases. There were 17 well, 16 moderately and 10 poorly differentiated carcinomas. In 31 of 32 patients with negative nodes no occult metastases could be identified. One patient with poorly differentiated stage C cancer demonstrated occult nodal deposits by prostate specific acid phosphatase and not by prostate specific antigen. In the 11 stage D1 cancer patients immunohistochemical staining confirmed all malignant deposits and additional metastatic lesions were detected in only 1 patient. Unlike other carcinomas, such as breast, in which immunohistochemical staining yields a 14 to 37% occult metastasis rate, these data suggest that occult nodal metastases are infrequently seen in carcinoma of the prostate.

The goal of this study was to determine if patients with stage D0-3 prostatic adenocarcinoma have detectable hematogenous micrometastasis. Polymerase chain reaction amplification of prostate-specific antigen mRNA, which is exclusively expressed by prostatic epithelial cells, was used to detect circulating prostatic cells. Peripheral venous blood was obtained from 17 control and 12 prostate cancer patients with stage D0-3 prostatic adenocarcinoma. Of the 12 cancer cases, four patients (stage D1-3) tested positive for prostate-specific antigen RNA, indicating the presence of circulating micrometastasis. The 17 negative controls all tested negative. Contrary to a long held hypothesis, these data point to the possibility that hematogenous metastasis may be a relatively early event in the natural history of human prostate cancer. These findings may have an important impact on our understanding and treatment of prostate cancer.

The mucin lining of the bladder is thought to serve as a primary defense mechanism against bacterial colonization, and has recently been implicated in the urothelial resistance to carcinogenic insult. We have isolated a unique glycoprotein fraction (GP1) of this lining from the normal rabbit bladder which may have a function in preventing bacterial adherence and colonization in the urinary tract. This glycoprotein has been shown to bind to a wide range of uropathic bacteria. The present study examines changes in the bladder's antibacterial defense mechanisms as measured by GP1 expression in the neoplastic state. Using an anti-GP1 serum, immunohistochemical staining was performed on 20 paraffinized and fresh frozen transitional cell carcinomas ranging from low grade, superficial tumors to high grade, invasive tumors. The presence of GP1 was seen throughout the mucosal layer in normal specimens with increased amounts noted towards the mucosal surface. Progressively decreased expression was noted with increasing grades of all transitional carcinoma specimens. Mucosal field changes in GP1 expression were not noted in any of the patients. Intestinal mucosal controls failed to detect the presence of GP1. These studies suggest that the expression of GP1 decreases with tumor dedifferentiation and that bladder tumorogenesis may serve a role in handicapping the bladder's primary antibacterial defense mechanism.

From 1978 through 1987, 78 patients with carcinoma of the bladder were treated with combined pre- and postoperative adjuvant radiation therapy. All were given a single dose of pre-operative radiation therapy, 500 cGy, either on the day of or the day before cystectomy. Histological staging on the cystectomy specimens according to the TNM classification system was performed. Forty patients with Stage P2 (high grade III and IV), P3A, P3B, P4A, or N+ underwent planned high dose postoperative radiation therapy (4000-4500 cGy) in 5 weeks. The whole pelvis was treated with conventional fractionation of 180 cGy 5 days per week. Median follow-up was 52 months, with 36 months minimum follow-up. There was a 67% overall 5-year survival, and those with P1 and P2 (Grade I and II) had an 84% 5-year survival. Survival for patients with P2 tumor (Grade III and IV), P3A, P3B, and P4/N+ stages was 57%, 56%, 39%, and 50%, respectively. Bowel obstructions developed in 8% of patients who received no postoperative radiation therapy and 37% in those who did. Genitourinary complication rates were similar in both groups, 13% in the group that received no postoperative radiation therapy and 10% in the group that did. Although the planned approach of combined pre- and postoperative radiation therapy for unfavorable stages of bladder cancer is associated with a better than 50% 5-year survival rate (except in Stage P3B cancer), the bowel toxicity was unacceptably high.

Pentosanpolysulfate (PPS) represents the product obtained after sulfation of xylan and is composed of beta 1----4-D-xylopyranose residues sulfated at C2 and C3. Studies have shown that this compound can often be effective in relieving the symptoms of interstitial cystitis (IC). In order to elucidate the mode of action of PPS in IC, a sensitive and reliable assay was needed. To this end we prepared an immunogenic form of PPS by coupling it to methylated bovine serum albumin (MBSA). This complex was used to immunize NZW rabbits (1 mg, IM). Four of five animals responded with anti-PPS antibodies, three of which had high titer (greater than 1/2000) as measured by an enzyme-linked immunosorbent assay (ELISA). All sera were routinely absorbed with an MBSA-Sepharose immunoadsorbent to remove anti-MBSA antibodies. ELISA inhibition tests were used to determine the sensitivity and specificity of the sera. At least 50 ng/ml of PPS could be routinely detected by this assay. A number of naturally occurring proteoglycans, polysaccharides, monosaccharides and disaccharides were examined for reactivity with the antibodies but only heparin was an effective inhibitor. Absorption with heparin immunoadsorbents reduced, but did not eliminate, the ability of heparin to inhibit anti-PPS binding. This activity could be destroyed by treatment with heparinase without affecting PPS inhibition. Normal urine did not affect the ELISA or ELISA inhibition tests and thus allowed the determination of PPS levels in IC patient urines. Initial analysis of seven IC patients receiving oral PPS revealed urine concentration of 0.8-16.0 micrograms/ml. No inhibition could be detected in pre-treatment urine samples.

The subject of genitourinary cancer in the elderly becomes increasingly more important as our population of patients older than 50 years expands. Carcinoma of the kidney, bladder, and prostate all have an increasing incidence over the age of 50 and have a predilection for afflicting men more commonly than women. Etiologic factors, especially with bladder and kidney carcinomas, are well documented and in some cases preventable. Screening the urine for hematuria and careful digital rectal examinations may uncover a higher percentage of these malignancies in earlier, more curable stages. Recent advances in the treatment of all of these malignancies have improved survival and quality of life for these patients.

Pentosan polysulfate sodium (PPS) was compared with placebo for the symptomatic therapy of interstitial cystitis in a double-blind, multicenter study. A total of 110 patients were enrolled and treated for three months. In this study, overall improvement of greater than 25 percent was reported by 28 percent of the PPS-treated patients and by 13 percent of the placebo-treated patients (p = 0.03). The investigators' overall evaluation provided similar results, 26 percent vs 11 percent in favor of PPS (p = 0.04). Improvement in pain and pressure to urinate also favored PPS over placebo and approached statistical significance (p = 0.07 and 0.08). The incidence of adverse reactions was 6 percent in the PPS-treated group and 13 percent in the placebo-treated group. All adverse reactions were minor, and treatment was discontinued by 1 patient in the PPS group and 2 in the placebo group. In this study, PPS was found to be significantly more effective than, and equally as safe as, placebo.

The incidence of bacteriuria increases in men and women with age. Its association with multiple geriatric disorders makes it difficult to determine its relevance in the absence of cause-related symptoms. A direct relationship to morbidity and mortality is debatable except in very specific patients. Confronted with symptoms, the clinician should treat and manage UTIs as in the younger patient with careful selection of an antimicrobial drug. Diagnosis can often be rapid and inexpensive. Further evaluation should be undertaken only in specific instances. Perinephric abscess is uncommon but seen in increasing incidence in older, especially female, patients. This disorder can more accurately be diagnosed with new techniques. Successful management with percutaneous procedures has reduced the need for higher risk open surgical procedures. Improved methods of diagnosis and treatment have decreased mortality in the past decade.

The mucin layer covering the bladder transitional cell mucosa appears to function as a primary defense mechanism against bacterial infection. We have previously prepared a glycoprotein fraction (GP1) from the urinary bladder mucosa of NZW rabbits and raised murine antisera against it. These antisera react with bladder, ureter and kidney tissue from rabbits, rats, guinea pigs, and hamsters. We now show that a similar substance occurs in human kidneys and bladder. In order to remove antibodies reactive with the Tamm-Horsfall protein (THP), the antisera were initially absorbed with an immunoadsorbent composed of purified human THP covalently bound to Sepharose CL-4B gel. Using an enzyme linked immunosorbent assay (ELISA) it could be shown that the absorbed antisera did not react with THP but retained a high titer in binding to GP1. Immunohistochemical procedures involving avidin-biotin-immunoperoxidase staining demonstrated that the absorbed anti-GP1 reacted well with six human urinary bladder biopsy specimens and two kidney autopsy specimens while normal murine sera showed little or no binding. Although this reactivity was not as strong as that found with homologous tissue (rabbit) these studies suggest that GP1, an antigen common to several animal species, is also related to a human urinary tract component.

Thirty-nine patients with invasive bladder cancer were treated using a new approach to adjuvant radiation therapy. All patients had histologic evidence of bladder muscle invasion on biopsy and were considered suitable for surgical resection. Low-dose preoperative radiation (500 rad) was delivered either on the day of or the day before cystectomy. In most instances, a radical cystectomy was performed and patients were then stratified according to pathologic stagings. Those patients with pathologically good prognostic indicators, Stage B1 low grade (I or II) disease, were followed up with no further treatment. Patients at high risk for local recurrence and pelvic lymph node involvement, Stages B1 high grade (III or IV), B2, and C, were given aggressive postoperative radiation (4,500 rad in five weeks). Patients with advanced disease, Stage D2, were given palliative therapy. All patients received the dose of preoperative radiation as planned. Preliminary results indicate that combined pre- and postoperative radiation in bladder cancer gives excellent local control of disease. A significant potential for improved long-term survival of patients has been observed.

During the past ten years, 18 nonfunctioning adrenal tumors have been removed. The significance of these lesions may be unknown to the urologist because reported cases and series are few and pathologic possibilities are numerous. The significant percentage of carcinoma is demonstrated in this series. Presentation, workup, pathology, and operative approaches are discussed.

We recently established a multidisciplinary center for the evaluation and treatment of male sexual dysfunction. The patients are seen in a single day by the endocrinologist, psychiatrist, psychologist, neurophysiologist and urologist. Laboratory studies include chemical and hormonal profiles, pudendal nerve latency testing and determination of the penile blood pressure. Nocturnal penile tumescence studies are done in selected cases. A diagnosis was made in 95 of 106 patients (90 per cent). The problem was psychogenic in 42 per cent of the patients, vascular and neurologic in 34 per cent, hormonal in 15 per cent, urologic in 7 per cent and medication-related in 2 per cent. The interdisciplinary approach to this problem allows for a more comprehensive and accurate evaluation, while providing a convenient service to the patient.

Infection rates have been determined in a 332 bed university hospital using an efficient surveillance program. This computerized program analyzed, summarized and returned infection reports in six days. The efficiency rate of this system was 80 per cent as determined by prevalence survey. The mean nosocomial infection rate for the 12 month study period was 10.8 per cent. Neurology, medicine, neurosurgery, surgery and urology ahd the highest attack rates. Urinary tract infections composed 44 per cent of the total and predominated on seven of the 11 services. Escherichia coli predominated in infections of the urinary tract, surgical wounds and blood and ranked third in respiratory infections. Escherichia coli, klebsiella, pseudomonas and proteus mirabilis accounted for 61 per cent of the isolates. There is a need for efficient reporting of hospital infections to establish effective preventives.

Histochemical staining of bladder tissue has demonstrated a discrete layer of mucopolysaccharide (mucin) at the surface of rabbit and human bladders. This mucin is disrupted by acid treatment and is probably resynthesized by the transitional cells in less than twenty-four hours and replaced by forty-eight hours. Physiologic data indicate that bladder mucose can resist bacterial attachment, a function that is also disrupted by acid and recovers in less than twenty-four hours. These findings suggest that the surface mucopolysaccharide inhibits bacterial binding and may be the primary antibacterial defense of the urinary tract.

Oral methylene blue therapy was not effective in dissolving non-obstructive renal calculi in 26 patients but it may prevent new stone formation in patients with metabolically active urolithiasis. The use of methylene blue therapy in combination with other regimens having different mechanisms of stone inhibition is recommended to further improve results.

Urinary glycoconjugates (glycosaminoglycans, glycoproteins, mucopolysaccharides) have been postulated as the natural defense mechanisms which prevent urinary tract infections. As a direct approach to establish the validity of this hypothesis, we have prepared a glycoprotein fraction (GP1) from rabbit bladder mucosal tissue and shown that it may be involved in the prevention of bacterial adherence. Immunohistochemical studies using fluorescence have demonstrated that murine antibodies raised to rabbit GP1 can be used as a semiquantitative index of glycoprotein production. The present investigation addresses the question of the species restriction of the glycoprotein--whether it is confined to the rabbit or whether a similar or identical substance occurs in other species. Using an immunoperoxidase staining technique, we have examined the genitourinary tracts of Sprague Dawley rats, Golden hamsters, and Hartley guinea pigs. Mouse anti-rabbit GP1 was used as the primary antibody with an avidin-biotin complexing system. All three species reacted well with the murine antiserum but were negative with normal sera. Semiquantitative estimates of the relative amounts of this material in different areas of the genitourinary tract showed that the distal renal tubules, renal pelvic mucosa, ureters and bladders were rich in this glycoprotein while urethra and vagina were not.

Peanut lectin (PNA) binds to D Gal B (1-3) D Gal NAc which is the purported antigenic determinant of the so-called T blood group antigen (TAg). We used PNA in an indirect immunofluorescent technique to study TAg in transitional cell carcinomas of the bladder (TCC). All 14 control tissues failed to express TAg, whereas all controls (100%) expressed TAg on the cell membrane after prior treatment with neuraminidase. Sixty-nine percent of Stage O TCC expressed TAg, whereas 100% of cases expressed TAg after treatment with neuraminidase. Staining patterns noted were: granular intracytoplasmic, intracytoplasmic globular, and membrane. There was no correlation between TAg positivity or negativity and subsequent muscle wall invasion in the Stage O TCC group. Fifty percent of Stage B or greater TCC expressed TAg, whereas 27 of 30 (90%) cases expressed TAg after neuraminidase treatment. TAg-staining patterns noted in Stage B tumors were: membrane, granular intracytoplasmic, intracytoplasmic globular, and glycocalyx. Only 47% of Grade III TCC expressed TAg compared with 72% of low-grade TCC. The authors conclude that the expression of TAg reflects the neoplastic transformation of bladder epithelium. The data also suggest that in TCC, TAg positivity is most likely due to incomplete synthesis of MN blood group glycoprotein, as evidenced by loss of a terminal sialic acid, and that there is also evidence of cytostructural "relocalization" of TAg.

We have previously shown that the transitional cells lining the urinary bladder are capable of producing glycosaminoglycan (GAG). By use of a quantitative in vivo method of measuring bacterial adherence, we demonstrated that bacterial adherence to the mucosal cells is diminished in the presence of this GAG, rises when it is removed (by acid), and returns to normal when the GAG is resynthesized (in less than 24 h). We also found that this much layer could be removed (with a corresponding rise in bacterial adherence) and that addition of exogenous GAG (heparin) to the bladder prevented the expected rise in bacterial adherence. This study analyzed in depth the manner by which heparin prevents the rise in adherence seen when the mucin is removed. Pretreatment of bacteria with heparin had no effect on adherence, whereas pretreatment of the bladder with heparin inhibited adherence. To corroborate our impression that the heparin was coating the transitional cells, [3H]heparin was added to bladders after removal of mucin. Autoradiography revealed the heparin to be adherent to the surface of the transitional cells.

To implicate further the surface mucoprotein as the factor responsible for preventing bacterial attachment to the bladder mucosa, rabbit urothelium was severely disrupted and allowed to regenerate for varying periods of time. Quantitative measurements of the attachment of 14C-labeled Escherichia coli were correlated with the histologic presence of the surface mucoprotein. Control levels of bacterial attachment were observed only when the PAS-positive layer had regenerated, further supporting the role of this layer in the bladder's antibacterial defense.

Four patients with 5 nonopaque renal calculi composed of uric acid were examined by ultrasound. The calculi varied in size from a 1.5 X 1.5-cm intrapelvic stone to a staghorn calculus measuring 4 cm. All stones were satisfactorily imaged by ultrasound, allowing a diagnosis of nephrolithiasis to be made with confidence in each case. In 2 patients with poor excretion on urography, the diagnosis was not suspected prior to the ultrasound examination. The authors feel that ultrasound has great potential value in the investigation of nonopaque filling defects of the renal pelvis and in patients with urographic nonvisualization who have a high risk of uric acid lithiasis.

Previous studies performed in our laboratory indicated that the primary antibacterial defense mechanism of the rabbit bladder is the antiadsorptive action of the surface mucopolysaccharide. The increased bacterial adsorption that occurs when the bladder is denuded of this layer was prevented by the instillation of heparin. Additional studies showed that the protective effect of heparin is inhibited by protamine, a further indication that the bladder's "antiadherence factor" is a mucopolysaccharide. Small amounts of heparin, applied directly to the mucoprotein-deficient bladder or to the surface of the inoculated bacteria, produced a statistically significant reduction in bacterial adsorption.

Changing concepts regarding the epidemiology, pathogenesis, evaluation, and treatment of urinary tract infection have reduced patient expenditures. An appreciation of the natural history and associated significance of these infections at all ages in both male and female patients is essential for proper evaluation and treatment. Careful classification of the infection with attention to historical aspects allows the clinician to plan a treatment regimen tailored to each patient. When and how these patients are evaluated depend on the statistical likelihood of associated pathology.

The radiation therapy oncology group (RTOG) has conducted two studies testing the value of extended-versus limited-fields in carcinoma of the prostate. RTOG protocol 75-06 tests the value of paraaortic irradiation in patients with locally advanced tumors limited to the pelvis. RTOG protocol 77-06 tests the value of pelvic irradiation in patients with tumors limited to the prostate. Two hundred sixty-eight evaluable patients have been entered on RTOG 75-06, and 219 on RTOG 77-06 prior to 1981. This is a preliminary report on treatment-related morbidity in patients followed for a minimum of 1 year. Treatment-related morbidity has been classified according to a five-grade severity classification schema and correlated with the protocol option assignment in order to determine whether the use of extended fields had an effect on the incidence of side effects. Thirty-one percent of 268 patients on RTOG 75-06 and 34% of 219 patients on RTOG 77-06 had some form of treatment side effects. The majority (over 80%) of these were mild (grade 1 and 2) and by definition did not interfere with the patients' performance (life style). Only three patients on RTOG 75-06 and one on RTOG 77-06 had grade 4 complications (by definition requiring a surgical intervention). No fatal (grade 5) complications have been recorded so far. The use of paraaortic fields in RTOG 75-06 and pelvic fields in RTOG 77-06 have not resulted in a significant increase of GI or GU morbidity at this time. The only statistically significant trend was the incidence of postirradiation genital and lower extremity edema which strongly correlated with the extent of staging lymphadenectomy.

With the increasing use of pelvic node dissection for staging and treating pelvic urological cancer injury to the common, external and internal iliac veins will occur. The sequelae of these injuries are described and the treatment is outlined. A case is described that epitomizes the problems and solutions of this condition.

14C-labeled Escherichia coli was introduced into acid-treated and intact rabbit bladders in vivo. Live, dead, and metabolically inhibited bacteria displayed similar interaction with the urothelium with and without intact surface mucoprotein. Disruption of the mucoprotein layer by acid reduced the defense potential in each group to a similar degree. Neither active metabolism nor bacterial cell death seems to enhance bacterial adherence to bladder mucosa.