Phase i study of intravesical vaccinia virus as a vector for gene therapy of bladder cancer.

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.

Does hormonal therapy influence sexual function in men receiving 3D conformal radiation therapy for prostate cancer?

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.

Interaction of bladder glycoprotein GP51 with uropathogenic bacteria.

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.

Transurethral microwave thermotherapy of the prostate without intravenous sedation: results of a single United States center using both low- and high-energy protocols. TJUH TUMT Study Group.

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 multidisciplinary clinic approach to prostate cancer counseling and treatment.

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.

Hospital-acquired urinary tract infections associated with the indwelling catheter.

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.

The efficacy of early adjuvant radiation therapy for pT3N0 prostate cancer: a matched-pair analysis.

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.

The urinary glycoprotein GP51 as a clinical marker for interstitial cystitis.

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.

Durable efficacy of early postoperative radiation therapy for high-risk pT3N0 prostate cancer: the importance of radiation dose.

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.

Effect of higher radiation dose on biochemical control after radical prostatectomy for PT3N0 prostate cancer.

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.

Utilization of autologous blood donation during radical retropubic prostatectomy.

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.

Stage T3 prostate cancer: a nonrandomized comparison between definitive irradiation and induction hormonal manipulation plus prostatectomy.

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 invention of the modern uroflowmeter by Willard M. Drake, Jr at Jefferson Medical College.

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.

Postoperative epidural analgesia following radical retropubic prostatectomy: outcome assessment.

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.

Induction androgen deprivation plus prostatectomy for stage T3 disease: failure to achieve prostate-specific antigen-based freedom from disease status in a phase II trial.

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.

Urinary tract glycoprotein: distribution and antigenic specificity.

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.

The effect of intermittent pneumatic compression devices on intraoperative blood loss during radical prostatectomy and radical cystectomy.

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.

Screening for occult nodal metastasis in localized carcinoma of the prostate.

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.