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Objective: To assess whether a multimodal opioid-limiting protocol and patient education intervention can reduce postoperative opioid use following transurethral resection of the prostate., Methods: This prospective, non-blinded, single-institution, randomized controlled trial (NCT04102566) assigned 50 patients undergoing a transurethral resection of the prostate to either a standard of care control (SOC) or multimodal experimental group (MMG). The intervention included adding ibuprofen to the postoperative pain regimen, promoting appropriate opioid use while hospitalized, an educational intervention, and discharging without opioid prescription. Data regarding demographics, operative data, opioid use, pain scores, and patient satisfaction were compared., Results: A total of 47 patients were included, n = 23 (MMG) and n = 24 (SOC). Demographic and operative findings were similar. Statistical analysis for noninferiority demonstrated non-inferior inpatient pain control (mean pain score 2.5 MMG vs 2.4 SOC, P = 0.0003). The multimodal group used significantly fewer morphine milligram equivalents after discharge (0 vs 4.1, P = 0.04). Inpatient use was reduced but did not reach statistical significance (6.0 vs 9.8, P = 0.2). Mean satisfaction scores with pain control were similar (9.6 MMG vs 9.2 SOC, P = 0.32). No opioid prescriptions were requested after discharge. Adverse events and medication side effects were infrequent and largely similar between groups., Conclusion: Implementation of an opioid-limiting postoperative pain protocol and patient education resulted in no outpatient opioid use while maintaining patient satisfaction with pain control. Eliminating opioids following a common urologic procedure will decrease risk of opioid-related adverse events and have a positive downstream impact., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Background: Ureteral identification is essential to performing safe colorectal surgery. Injected immunofluorescence may aid with ureteral identification, but feasibility without ureteral catheterization is not well described., Methods: Case series of robotic colorectal resections where indocyanine green (ICG) injection with or without ureteral catheter placement was performed. Imaging protocol, time to ureteral identification, and factors impacting visualization are reported., Results: From 2019 to 2020, 83 patients underwent ureteral ICG injection, 20 with catheterization and 63 with injection only. Main indications were diverticulitis (52%) and cancer (36%). Median time to instill ICG was faster with injection alone than with catheter placement (4min vs 13.5min, p < 0.001). Median time [IQR] to right ureter (0.3 [0.01-1.2] min after robot docking) and left ureter (5.5 [3.1-8.8] min after beginning dissection) visualization was not different between injection alone and catheterization., Conclusion: ICG injection alone is faster than with indwelling catheter placement and equally reliable at intraoperative ureteral identification., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Serological assays intended for diagnosis, sero-epidemiologic assessment, and measurement of protective antibody titers upon infection or vaccination are essential for managing the SARS-CoV-2 pandemic. Serological assays measuring the antibody responses against SARS-CoV-2 antigens are readily available. However, some lack appropriate characteristics to accurately measure SARS-CoV-2 antibodies titers and neutralization. We developed an Enzyme-linked Immunosorbent Assay (ELISA) methods for measuring IgG, IgA, and IgM responses to SARS-CoV-2, Spike (S), receptor binding domain (RBD), and nucleocapsid (N) proteins. Performance characteristics of sensitivity and specificity have been defined. ELISA results show positive correlation with microneutralization and Plaque Reduction Neutralization assays with infectious SARS-CoV-2. Our ELISA was used to screen healthcare workers in Louisville, KY during the first wave of the local pandemic in the months of May and July 2020. We found a seropositive rate of approximately 1.4% and 2.3%, respectively. Our analyses demonstrate a broad immune response among individuals and suggest some non-RBD specific S IgG and IgA antibodies neutralize SARS-CoV-2., (© 2021. The Author(s).)

Purpose: Despite low rates of transfusion associated with robotic prostatectomy, surgeons routinely obtain preoperative blood typing. Here we aim to understand the cost savings associated with eliminating blood typing prior to prostatectomy., Materials and Methods: A retrospective review of our single surgeon radical prostatectomy database was performed. Patients receiving blood transfusions within 3 days of prostatectomy were identified and clinical characteristics were recorded. Cost information was obtained, and descriptive statistical analysis performed., Results: 1,581 patients underwent prostatectomy from 2000 to 2019. Thirty-two patients (2.02%) received a transfusion within 3 days of surgery. The transfusion rate for open prostatectomy was 3.21% vs 1.37% for robotic prostatectomy. The cost of preoperative blood typing for all radical prostatectomies was $113,832, or about $5,812.70 per year., Conclusions: Transfusion rates for prostatectomy are low and decline with experience. Significant cost savings is possible by avoiding routine preoperative blood typing in most patients undergoing radical prostatectomy.

The "whole genome" TMV-based expression system, Geneware®, was used in the cGMP production of the plant-made pharmaceutical Q-Griffithsin and demonstrates stable expression for up to a two-year period. Virion and plasmid banks which contained viral cDNA and a Q-Griffithsin sequence were able to produce >200 g of Q-Griffithsin. Data assessing the quality and stability of the product banks were measured through functional assessments of visual symptomology and product expression., Competing Interests: Declaration of Competing Interest KEP, JLF, and KTH are inventors on patents and patent applications that claim Q-GRFT composition and utility. In addition, KEP, JLF, and KTH are founders and equity holders in GROW Biomedicine LLC, which is commercializing Q-GRFT. EH, JMC, JWS declare no conflicts of interest., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Introduction: In this quality initiative we assessed whether providing surgeons with the American Urological Association guideline regarding intravesical mitomycin C at the time of surgery scheduling impacts compliance. Furthermore, we examined the durability of the intervention and the influence of surgeon volume on guideline adherence., Methods: All patients (105) undergoing transurethral bladder tumor resection from July 2015 to February 2016 at Virginia Mason Medical Center were included prospectively. At the scheduling of surgery urologists were provided with a preoperative tool that included the relevant guideline. Mitomycin C use during the study period was compared to historical and subsequent year's use. Additionally, we stratified results by high and low volume resectionists., Results: Before this study mitomycin C was used in 17.1% (25 of 146) of all resections. During the intervention period its use nearly tripled to 43% (28 of 65), an increase of 25.9%. The year after the intervention its use decreased to 32.7% (36 of 110). Durability was strongest for high volume surgeons and trended toward significance for low volume surgeons., Conclusions: Providing surgeons with a copy of the guideline at the time of surgery scheduling resulted in a threefold increase in guideline compliance. This change is durable and most impactful for higher volume surgeons. We believe this model can be used to ensure adherence and consideration for many guidelines.

Objective: To review the pioneering contributions of Dr. Robert Gibbons of Virginia Mason Medical Center to the evolution and development of the modern ureteral stent., Methods: We reviewed Dr. Gibbons' extensive work through primary sources, including interviews, projector slides, radiology images, stent prototypes, his personal writings, and archived documents. In addition, we performed a review of historical texts and manuscripts describing important innovations in the development of the ureteral stent., Results: In 1972, motivated by a desire to provide his patients with a long-term alternative to open nephrostomy and inspired by Drs. David Davis and Paul Zimskind, who in 1967 had described the use of indwelling ureteral silicone tubing, Dr. Gibbons began to experiment with modifications to improve upon existing stents. To address distal migration, Dr. Gibbons added "wings" that collapsed as the stent was advanced and expanded once in proper position to secure the stent in place. Barium was embedded into the proximal tip to facilitate radiographic visualization. A flange was added to the distal end, preventing proximal migration and minimizing trigonal irritation, and a tail was attached to aid in stent removal. The result was the original Gibbons stent, the first commercially available ureteral stent, and the establishment of Current Procedural Terminology code 52332, still used today., Conclusion: The ureteral stent is a fundamental component of urologic practice. In developing the Gibbons stent, Dr. Gibbons played a pivotal role in addressing the challenge of internal urinary diversion particularly for those who needed long-term management. Urologists and the patients they serve owe Dr. Gibbons and other surgeon-inventors a debt of gratitude for their innovative work., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Introduction: Shared decision making (SDM) is widely encouraged by both the American Urological Association and Choosing Wisely for prostate cancer screening. Implementation of SDM is challenging secondary to time constraints and competing patient priorities. One strategy to mitigate the difficulties in implementing SDM is to utilize a decision aid (DA). Here we evaluate whether a DA improves a patient's prostate cancer knowledge and affects prostate-specific antigen (PSA) screening rates., Materials and Methods: Patients were randomized to usual care (UC), DA, or DA + SDM. Perception of quality of care was measured using the Consumer Assessment of Healthcare Providers and Systems (CAHPS) survey. Outcomes were stratified by long term provider relationship (LTPR, > 3 years) versus short term provider relationship (STPR, < 3 years). Knowledge of prostate cancer screening and the decision regarding screening were assessed. Groups were compared using ANOVA and logistic regression models., Results: A total of 329 patients were randomized. Patients in the DA + SDM arm were significantly more likely to report discussing the implication of screening (33% DA + SDM, 22% UC, 16% DA, p = 0.0292) and answered significantly more knowledge questions correctly compared to the UC arm (5.03 versus 4.46, p = 0.046). However, those in the DA arm were significantly less likely to report that they always felt encouraged to discuss all health concerns (72% DA, 78% DA + SDM, 87% UC, p = 0.0285). Interestingly, STPR patients in the DA arm were significantly more likely to undergo PSA-based prostate cancer screening (41%) than the UC arm (8%, p = 0.019). This effect was not observed in the LTPR group., Conclusions: Providing patients a DA without a personal interaction resulted in a greater chance of undergoing PSA-based screening without improving knowledge about screening or understanding of the consequences of this decision. This effect was exacerbated by a shorter term provider relationship. With complex issues such as the decision to pursue PSA-based prostate cancer screening, tools cannot substitute for direct interaction with a trusted provider.

Purpose: STAND, a randomized, phase II, open-label trial (NCT01431391), assessed sequencing of sipuleucel-T (an autologous cellular immunotherapy) with androgen deprivation therapy (ADT) in biochemically recurrent prostate cancer (BRPC) patients at high risk for metastasis. Experimental Design: Men with BRPC following prostatectomy and/or radiotherapy, a PSA doubling time ≤12 months, and no metastasis were enrolled. Patients were randomized (34/arm) to sipuleucel-T followed by ADT (started 2 weeks after sipuleucel-T completion), or ADT followed by sipuleucel-T (started 12 weeks after ADT initiation); ADT continued for 12 months in both arms. The primary endpoint was PA2024-specific T-cell response [enzyme-linked immunospot (ELISPOT)] over time. Results: PA2024-specific ELISPOT responses over time were similar between groups, except at week 6, where responses were higher with sipuleucel-T→ADT versus ADT→sipuleucel-T ( P = 0.013). PA2024-specific T-cell proliferation responses, averaged across time points, were approximately 2-fold higher with sipuleucel-T→ADT versus ADT→sipuleucel-T ( P = 0.001). PA2024-specific cellular and humoral responses and prostatic acid phosphatase-specific humoral responses increased significantly versus baseline ( P < 0.001) and were maintained for 24 months (both arms). Median time-to-PSA recurrence was similar between arms (21.8 vs. 22.6 months, P = 0.357). Development of a PA2024-specific humoral response correlated with prolonged time-to-PSA progression (HR, 0.22; 95% CI, 0.08-0.67; P = 0.007). Sipuleucel-T with ADT was generally well tolerated. Conclusions: Sipuleucel-T→ADT appears to induce greater antitumor immune responses than the reverse sequence. These results warrant further investigation to determine whether this sequence leads to improved clinical outcomes, as well as the independent contribution of ADT alone in terms of immune activation. Clin Cancer Res; 23(10); 2451-9. ©2016 AACR ., (©2016 American Association for Cancer Research.)

Background: The current study was conducted to determine the feasibility of cytologically clearing the bladder of tumor cells after transurethral resection of bladder tumor (TURBT) and aggressive serial bladder washing., Methods: A prospective pilot sample of 20 patients with known bladder masses was enrolled before undergoing TURBT. Preoperative cytology and 4 postoperative cytology specimens were assessed for malignant cells between serial bladder washes. Surgeons assessed tumor grade visually at the time of TURBT., Results: Surgeons were able to differentiate high-grade disease with limited accuracy (75% sensitivity, 92% specificity, 85% negative predictive value, and 86% positive predictive value). For patients with low-grade disease (12 patients), cytology was atypical in 25% of patients immediately before TURBT and was negative after serial washings in all patients. In patients with high-grade disease (8 patients), approximately 75% had cytology consistent with high-grade urothelial carcinoma immediately before TURBT and only 1 patient was cleared cytologically after serial bladder washings., Conclusions: In patients with high-grade disease, serial bladder washing after TURBT does not appear to clear malignant cells as detected by cytology. This theoretical oncologic risk should be weighed when considering concomitant upper tract procedures such as retrograde pyelography. Future work is needed to quantify risk. Cancer Cytopathol 2017;125:114-119. © 2016 American Cancer Society., (© 2016 American Cancer Society.)

Background: Local infiltration of CD8(+) T cells (CTLs) in tumor lesions predicts overall clinical outcomes and the clinical benefit of cancer patients from immune checkpoint blockade. In the current study, we evaluated local production of different classes of chemokines in prostate cancer lesions, and the feasibility of their modulation to promote selective entry of CTLs into prostate tumors., Methods: Chemokine expression in prostate cancer lesion was analyzed by TaqMan-based quantitative PCR, confocal fluorescence microscopy and ELISA. For ex vivo chemokine modulation analysis, prostate tumor explants from patients undergoing primary prostate cancer resections were cultured for 24 hr, in the absence or presence of the combination of poly-I:C, IFNα, and celecoxib (PAC). The numbers of cells producing defined chemokines in the tissues were analyzed by confocal microscopy. Chemotaxis of effector CD8(+) T cells towards the untreated and PAC-treated tumor explant supernatants were evaluated in a standard in vitro migration assays, using 24 well trans-well plates. The number of effector cells that migrated was enumerated by flow cytometry. Pearson (r) correlation was used for analyzing correlations between chemokines and immune filtrate, while paired two tailed students t-test was used for comparison between treatment groups., Results: Prostate tumors showed uniformly low levels of CTL/NK/Th1-recruiting chemokines (CCL5, CXCL9, CXCL10) but expressed high levels of chemokines implicated in the attraction of myeloid derived suppressor cells (MDSC) and regulatory T cells (Treg ): CCL2, CCL22, and CXCL12. Strong positive correlations were observed between CXCL9 and CXCL10 and local CD8 expression. Tumor expression levels of CCL2, CCL22, and CXCL12 were correlated with intratumoral expression of MDSC/Treg markers: FOXP3, CD33, and NCF2. Treatment with PAC suppressed intratumoral production of the Treg -attractant CCL22 and Treg /MDSC-attractant, CXCL12, while increasing the production of the CTL attractant, CXCL10. These changes in local chemokine production were accompanied by the reduced ability of the ex vivo-treated tumors to attract CD4(+) FOXP3(+) Treg cells, and strongly enhanced attraction of the CD8(+) Granzyme B(+) CTLs., Conclusions: Our data demonstrate that the chemokine environment in prostate cancer can be reprogrammed to selectively enhance the attraction of type-1 effector immune cells and reduce local attraction of MDSCs and Tregs . Prostate 76:1095-1105, 2016. © 2016 Wiley Periodicals, Inc., (© 2016 Wiley Periodicals, Inc.)

Purpose: We determined whether the characteristics of patients undergoing prostate needle biopsies and prostate needle biopsy results changed after the U.S. Preventive Services Task Force recommendation in 2012 against prostate specific antigen based screening for prostate cancer for men of any age., Materials and Methods: A prospective database of patients undergoing prostate needle biopsies at Virginia Mason from 2004 to 2014 was reviewed. Welch's t-test and chi-square tests were used to compare patients seen before to those seen after the USPSTF recommendation. Relative risks and corresponding confidence intervals were estimated by general linear regression., Results: Patients in the post-USPSTF group (310) had a higher prostate specific antigen (p <0.001), were more likely to be diagnosed with higher clinical stage (2b, p=0.003; 2c-3a, p=0.027) and D'Amico high risk prostate cancer (p=0.036), with an adjusted relative risk for high risk prostate cancer of 1.25 (95% CI 1.02-1.52) compared to those in the pre-USPSTF group (1,416). Limiting the pre-USPSTF group to the 30 months before the draft guidelines (448 patients) yielded similar results. The absolute number of biopsies performed decreased by 31%, with the majority of the decrease occurring in the detection of intermediate risk tumors., Conclusions: In the 2 and a half years after the USPSTF recommendation against prostate specific antigen based screening, patients undergoing prostate needle biopsies were significantly more likely to be diagnosed with high risk disease. However, a reduction in the number of prostate needle biopsies performed occurred concomitantly with a decrease in the detection of intermediate risk, potentially curable prostate cancer. Future focus on informed application of screening techniques may prevent the reversal of decades of improvement in the prostate cancer mortality rate., (Copyright © 2016 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.)

A 50-year-old man with benign prostatic hyperplasia and urinary retention had a very large diverticulum on the posterior wall of the bladder. The patient was managed with transurethral resection of the prostate and endoscopic fulguration of the bladder diverticulum mucosa using the Orandi technique. There was near-complete resolution of the bladder diverticulum following endoscopic management, obviating the need for bladder diverticulectomy. The patient now empties his bladder, with a postvoid residual < 50 mL and the absence of urinary tract infection after 6-month follow-up. We report the successful treatment of a large bladder diverticulum with endoscopic fulguration to near-complete resolution. This minimally invasive technique is a useful alternative in patients unfit for a more extensive surgical approach.

Objective: To collect and analyze quality-of-life (QOL) data from PROvenge Treatment and Early Cancer Treatment trial (PROTECT, NCT00779402), a phase III, randomized controlled trial of sipuleucel-T in patients with asymptomatic androgen-dependent prostate cancer., Methods: Patients experiencing prostate-specific antigen relapse after radical prostatectomy entered a 3- to 4-month run-in phase of androgen-deprivation therapy (ADT), followed by 2:1 randomization to sipuleucel-T or control. QOL was assessed throughout the run-in and 26-week post-randomization phases using the Brief Fatigue Inventory (BFI), Linear Analog Self-Assessment (LASA) scale, Global Rating of Change (GRoC) scale, and an elicited symptoms list., Results: One hundred seventy-six patients were randomized into 2 groups, the sipuleucel-T group (n = 117) or the control group (n = 59). The sample provided 80% power to detect a difference in fatigue interference score between treatment arms of 0.9 points. QOL declined predictably during ADT. At week 26, 26.2% of sipuleucel-T-treated patients and 21.6% of control-treated patients (P = .68) reported fatigue in the previous week, and the mean score for fatigue interference in the past 24 hours was 0.9 for both arms (P = .88). Results were comparable for usual fatigue (P = .91) and worst fatigue (P >.99). Mean LASA scores decreased in both groups (P = .26). The proportion of patients reporting better overall QOL on GRoC was similar (P = .62)., Conclusion: There is no clinically significant negative impact on QOL after sipuleucel-T treatment compared with control after a period of ADT in patients with asymptomatic androgen-dependent prostate cancer., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Background: Prostate cancer (PC) is the most commonly diagnosed noncutaneous malignancy in American men. PC, which exhibits a slow growth rate and multiple potential target epitopes, is an ideal candidate for immunotherapy. GVAX for prostate cancer is a cellular immunotherapy, composed of PC-3 cells (CG1940) and LNCaP cells (CG8711). Each of the components is a prostate adenocarcinoma cell line that has been genetically modified to secrete granulocyte-macrophage colony-stimulating factor. Hypothesizing that GVAX for prostate cancer could be effective in a neoadjuvant setting in patients with locally advanced disease, we initiated a phase II trial of neoadjuvant docetaxel and GVAX. For the trial, the clinical effects of GVAX were assessed in patients undergoing radical prostatectomy (RP)., Methods: Patients received docetaxel administered at a dose of 75 mg/m(2) every 3 weeks for 4 cycles. GVAX was administered 2-3 days after chemotherapy preoperatively for four courses of immunotherapy. The first dose of GVAX was a prime immunotherapy of 5×10(8) cells. The subsequent boost immunotherapies consisted of 3×10(8) cells. After RP, patients received an additional six courses of immunotherapy. Pathologic complete response, toxicity, and clinical response were assessed. The primary endpoint of the trial was a pathologic state of pT0, which is defined as no evidence of cancer in the prostate., Results: Six patients completed neoadjuvant docetaxel and GVAX therapy. No serious drug-related adverse events were observed. Median change in prostate-specific antigen (PSA) following neoadjuvant therapy was 1.47 ng/ml. One patient did not undergo RP due to the discovery of positive lymph nodes during exploration. Of the five patients completing RP, four had a downstaging of their Gleason score. Undetectable PSA was achieved in three patients at 2 months after RP and in two patients at 3 years after RP., Conclusions: Neoadjuvant docetaxel/GVAX is safe and well tolerated in patients with high-risk locally advanced PC. No evidence of increased intraoperative hemorrhage or increased length of hospital stay postoperatively was noted. These results justify further study of neoadjuvant immunotherapy.

Context: Prostate cancer patients at increased risk for relapse after prostatectomy were treated in a neoadjuvant study with androgen deprivation therapy (ADT) in combination with cixutumumab, an inhibitory fully human monoclonal antibody against IGF receptor 1 (IGF-IR)., Objective: A clinical trial with prospective collection of serum and tissue was designed to test the potential clinical efficacy of neoadjuvant IGF-IR blockade combined with ADT in these patients. The effect of body mass index (BMI) on response of IGF-IR/insulin components to IGF-IR blockade was also examined., Design: Eligibility for the trial required the presence of high-risk prostate adenocarcinoma. Treatment consisted of bicalutamide, goserelin, and cixutumumab for 13 weeks before prostatectomy. Here we report on an analysis of serum samples from 29 enrolled patients. Changes in IGF and glucose homeostasis pathways were compared to control samples from patients in a concurrent clinical trial of neoadjuvant ADT alone., Results: Significant increases were seen in GH (P = .001), IGF-I (P < .0001), IGF-II (P = .003), IGF binding protein (IGFBP)-3 (P < .0001), C-peptide (P = .0038), and insulin (P = .05) compared to patients treated with ADT alone. IGFBP-1 levels were significantly lower in the cixutumumab plus ADT cohort (P = .001). No significant changes in blood glucose were evident. Patients with BMIs in the normal range had significantly higher GH (P < .05) and IGFBP-1 (P < 0.5) levels compared to overweight and obese patients., Conclusions: Patients with IGF-IR blockade in combination with ADT demonstrated significant changes in IGF and glucose homeostasis pathway factors compared to patients receiving ADT alone. In the patients receiving combination therapy, patients with normal BMI had serum levels of glucose homeostasis components similar to individuals in the ADT-alone cohort, whereas patients with overweight and obese BMIs had serum levels that differed from the ADT cohort.

Prostate cancer is the most common cancer among men. The prospective discrimination of aggressive and clinically insignificant tumors still poses a significant and, as yet, unsolved problem. PITX2 DNA methylation is a strong prognostic biomarker in prostate cancer. Recently, a diagnostic microarray for prostate cancer prognosis based on PITX2 methylation has been developed and validated. Because this microarray requires nonstandard laboratory equipment, its use in a diagnostic setting is limited. This study aimed to develop and validate an alternative quantitative real-time PCR assay for measuring PITX2 methylation that can easily be established in clinical laboratories, thereby facilitating the implementation of this biomarker in clinical practice. A methylation cut-off for patient stratification was established in a training cohort (n = 157) and validated in an independent test set (n = 523) of men treated with radical prostatectomy. In univariate Cox proportional hazards analysis, PITX2 hypermethylation was a significant predictor for biochemical recurrence (P < 0.001, hazard ratio = 2.614). Moreover, PITX2 hypermethylation added significant prognostic information (P = 0.003, hazard ratio = 1.814) to the Gleason score, pathological T stage, prostate-specific antigen, and surgical margins in a multivariate analysis. The clinical performance was particularly high in patients at intermediate risk (Gleason score of 7) and in samples containing high tumor cell content. This assay might aid in risk stratification and support the decision-making process when determining whether a patient might benefit from adjuvant treatment after radical prostatectomy., (Copyright © 2013 American Society for Investigative Pathology and the Association for Molecular Pathology. Published by Elsevier Inc. All rights reserved.)

Purpose: Sipuleucel-T is an autologous cellular immunotherapy. We review the safety of the leukapheresis procedure required for sipuleucel-T preparation and complications related to venous catheter use in the randomized, placebo controlled phase 3 IMPACT (IMmunotherapy for ProstAte Cancer Trial) study (NCT 00065442)., Materials and Methods: A total of 512 patients with asymptomatic or minimally symptomatic metastatic castrate resistant prostate cancer were enrolled in the study. All patients were scheduled to undergo 3 standard 1.5 to 2.0 blood volume leukapheresis procedures at 2-week intervals. Leukapheresis related adverse events and those related to venous catheter use were reviewed. Immune cell counts were examined throughout the treatment course., Results: Of 512 enrolled patients 506 underwent 1 or more leukapheresis procedures and were included in this analysis. Adverse events were comparable between the sipuleucel-T and control arms. Leukapheresis related adverse events were primarily associated with transient hypocalcemia (39.3%). Most leukapheresis related adverse events (97%) were of mild/moderate intensity. Median white blood cell count and absolute monocyte and lymphocyte counts were stable and within normal ranges throughout the treatment course. Of all patients 23.3% had a central venous catheter placed primarily for leukapheresis. Patients with vs without a central venous catheter had a higher risk of infection potentially related to catheter use (11.9% vs 1.3%, p <0.0001) and a trend toward a higher incidence of venous vascular events potentially related to catheter use, excluding the central nervous system (5.9% vs 2.1%, p = 0.06)., Conclusions: Adverse events related to leukapheresis are manageable and quickly reversible. The majority of patients can undergo leukapheresis without a central venous catheter. Central venous catheters are associated with an increased risk of infections and venous vascular events. Peripheral intravenous access should be used when feasible., (Copyright © 2013 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.)

Purpose: Sipuleucel-T, an autologous cellular immunotherapy, was investigated in a randomized, double-blind, controlled trial to determine its biologic activity in androgen-dependent prostate cancer (ADPC)., Experimental Design: Patients with prostate cancer detectable by serum prostate-specific antigen (PSA) following radical prostatectomy received 3 to 4 months of androgen suppression therapy, and were then randomized (2:1) to receive sipuleucel-T (n = 117) or control (n = 59). The primary endpoint was time to biochemical failure (BF) defined as serum PSA ≥ 3.0 ng/mL. PSA doubling time (PSADT), time to distant failure, immune response, and safety were also evaluated., Results: Median time to BF was 18.0 months for sipuleucel-T and 15.4 months for control (HR = 0.936, P = 0.737). Sipuleucel-T patients had a 48% increase in PSADT following testosterone recovery (155 vs. 105 days, P = 0.038). With only 16% of patients having developed distant failure, the treatment effect favored sipuleucel-T (HR = 0.728, P = 0.421). The most frequent adverse events in sipuleucel-T patients were fatigue, chills, and pyrexia. Immune responses to the immunizing antigen were greater in sipuleucel-T patients at Weeks 4 and 13 (P < 0.001, all) and were sustained prior to boosting as measured in a subset of patients a median of 22.6 months (range: 14.3-67.3 months) following randomization., Conclusions: No significant difference in time to BF could be shown. The finding of increased PSADT in the sipuleucel-T arm is consistent with its biologic activity in ADPC. Long-term follow-up will be necessary to determine if clinically important events, such as distant failure, are affected by therapy. Treatment was generally well tolerated.

Introduction: Robotic assisted laparoscopic radical prostatectomy (RALP) is a common treatment for localized prostate cancer. Despite a primary advantage of improved postoperative pain, patients undergoing RALP still experience discomfort. Belladonna, containing the muscarinic receptor antagonists atropine and scopolamine, in combination with opium as a rectal suppository (B & O) may improve post-RALP pain. This study evaluates whether a single preoperative B & O results in decreased postoperative patient-reported pain and analgesic requirements., Materials and Methods: Patients undergoing RALP at Virginia Mason Medical Center between November 2008 and July 2009 were offered the opportunity to enter a randomized, double-blind, placebo-controlled trial. Exclusion criteria included: glaucoma, bronchial asthma, convulsive disorders, chronic pain, chronic use of analgesics, or a history of alcohol or opioid dependency. Surgeons were blinded to suppository placement which was administered after induction of anesthesia. All patients underwent a standardized anesthesia regimen. Postoperative pain was assessed by a visual analog scale (VAS) and postoperative narcotic use was calculated in intravenous morphine equivalents., Results: Ninety-nine patients were included in the analysis. The B & O and control groups were not significantly different in terms of age, body mass index, operative time, nerve sparing status or prostatic volume. Postoperative pain was significantly improved during the first two postoperative hours in the B & O group. Similarly, 24-hour morphine consumption was significantly lower in patients who received a B & O. No adverse effects secondary to suppository placement were identified., Conclusion: Preoperative administration of B & O suppository results in significantly decreased postoperative pain and 24-hour morphine consumption in patients undergoing RALP.

Ongoing clinical trials provide promise for the introduction of immunotherapy into the armamentarium against prostate cancer, but the precise role for immunotherapy remains to be determined. Combinations of immunotherapies may be needed to improve the response rates and the duration of response. Investigators have begun to examine the effect of immunotherapy in combination with other standard treatment, including as an adjuvant to chemotherapy or radiotherapy and as a neoadjuvant agent before prostatectomy. Although many studies examine efficacy in men with metastatic hormone-refractory prostate cancer, there is some evidence for improved responses at earlier stages of disease: the ability of the tumor to evade the immune system may be lessened with lower tumor burden, or the immune system may already be weakened in men with later stages of disease.

Background: This open-label, multicenter, dose-escalation study evaluated multiple dose levels of immunotherapy in patients with metastatic hormone-refractory prostate cancer (HRPC). The immunotherapy, based on the GVAX platform, consisted of 2 allogeneic prostate-carcinoma cell lines modified to secrete granulocyte-macrophage-colony-stimulating factor (GM-CSF)., Methods: Dose levels ranged from 100 x 10(6) cells q28d x 6 to 500 x 10(6) cells prime/300 x 10(6) cells boost q14d x 11. Endpoints included safety, immunogenicity, overall survival, radiologic response, prostate-specific antigen (PSA) kinetics, and serum GM-CSF pharmacokinetics., Results: Eighty men, median age 69 years (range, 49-90 years), were treated. The most common adverse effect was injection-site erythema. Overall, the immunotherapy was well tolerated. A maximal tolerated dose was not established. The median survival time was 35.0 months in the high-dose group, 20.0 months in the mid-dose, group, and 23.1 months in the low-dose group. PSA stabilization occurred in 15 (19%) patients, and a >50% decline in PSA was seen in 1 patient. The proportion of patients who generated an antibody response to 1 or both cell lines increased with dose and included 10 of 23 (43%) in the low-dose group, 13 of 18 (72%) in the mid-dose group, and 16 of 18 (89%) in the high-dose group (P = .002; Cochran-Armitage trend test)., Conclusions: This immunotherapy was well tolerated. Immunogenicity and overall survival varied by dose. Two phase 3 trials in patients with metastatic HRPC are underway., ((c) 2008 American Cancer Society.)

Iatrogenic bladder injury is a recognized complication of gynecologic surgery and may result in significant morbidity when associated with intraperitoneal perforation. Accordingly, open surgical repair is commonly required. We present a case of delayed iatrogenic bladder injury involving a foreign body and describe an innovative technique for conservative management.

Introduction: With nerve-sparing techniques, patients undergoing a radical prostatectomy may avoid the morbidity of erectile dysfunction. Certain patients who are not candidates for nerve-sparing procedures may be eligible for nerve interposition grafts. While bilateral cavernosal nerve grafting after radical prostatectomy has shown efficacy, the effect of unilateral nerve grafting following prostatectomy remains unclear. We evaluate a large group of patients who underwent a unilateral cavernosal nerve replacement., Methods: Forty patients underwent unilateral nerve sparing surgery with concomitant contralateral cavernosal nerve replacement. Patients were selected for this procedure based upon preoperative nomogram risk assessment, endorectal MRI evidence of extra capsular disease (ECE) or intraoperative histology demonstrating margin positivity. Age, demographic data, Gleason score, clinical and pathologic stage and pre and post operative IIEF data was collected and prospectively analyzed., Results: Median follow-up was 19 months. Median change in IIEF scores was 7.5. Twenty-one of 29 patients (72%) report being able to penetrate after prostatectomy. Sixteen of those 21 (76%) continue to require PDE-5 inhibitors to facilitate penetration. Four of the 6 patients (67%) who were unable to have intercourse following cavernosal nerve replacement received adjuvant hormonal and/or radiation therapy. Twenty-eight patients (97%) reported numbness at the graft harvest site. One patient experienced a graft site infection. Two of 29 (7%) patients reported pain at the harvest site., Conclusion: Unilateral sural nerve grafting is a feasible and well-tolerated approach for patients who must undergo wide resection of a NVB. While men do show a decrease in their IIEF score, 76% are able to achieve penetration following surgery. The majority of men continue to require PDE-5 inhibitors to facilitate intercourse.

Background: Bladder neck contracture (BNC) following prostatectomy has been reported in 0.5-32% of cases. While the etiology of a BNC is unclear, several factors have been associated with this complication, including blood loss, devascularization of bladder neck tissue, poor mucosal apposition and urinary extravasation. To study the impact of urinary extravasation on BNC formation, we used postoperative drain output as a surrogate measure for anastomotic leakage., Methods: All patients undergoing a radical retropubic prostatectomy (RRP) or a robotic assisted radical prostatectomy (RARP) from January 2000 to April 2006 have been entered into a prospective review board-approved database. All RRP patients had their anastomosis performed in an interrupted fashion using six monofilament 2-0 sutures. All robotic-assisted radical prostatectomy anastomoses were performed in a running fashion using 2-0 monofilament sutures. A single, closed suction Jackson Pratt drain was placed over the surgical bed at the conclusion of the case. Post-operative drain outputs were recorded. All patients were evaluated at 3, 6, 9, 12 and 24 months post-operatively. All patients who reported a diminished urinary stream or incontinence were evaluated by office cystoscopy. The inability to navigate an 18 French cystoscope through the bladder neck was defined as a bladder neck contracture., Results: A total of 576 patients underwent a radical prostatectomy over this time span. Complete records were available for 535 (93%) of these patients. There were 21 bladder neck contractures (3.9%) overall. The post-operative drain output ranged from 5-5,465 ml (median 119 ml). Eight patients who had drain outputs less than 119 ml developed a BNC while 13 BNC developed in patients with Jackson Pratt drain output > 119 ml (P = 0.343). In patients who underwent an open RRP, 19/424 (4.5%) developed contractures while 2/108 (1.9%) RARP patients developed a BNC (P = 0.105)., Conclusion: The amount of post-operative drain output is not statistically associated with the development of a bladder neck contracture.

Background: Soft tissue radiation necrosis (STRN) is effectively treated with hyperbaric oxygen (HBO,), believed to result from stimulation ofangiogenesis in radiation-injured tissue. Thirty to forty HBO2 treatments are usually recommended for STRN. For various reasons, different hyperbaric facilities offer these treatments once or twice daily and from 5-7 days weekly. It is not known whether the clinical response differs as a result of the rate of administration of HBO2 treatments., Methods: Details of hyperbaric treatment courses of patients treated for radiation enteritis/proctitis (n = 65) and cystitis (n = 94) at a single institution were reviewed. Outcomes were compared with the total number of HBO2 treatments administered and also rate of treatment administration., Results: Responses were similar for both forms of STRN whether the patient averaged fewer or greater than 5 treatments per week, or even < or = 3 versus > or = 7 treatments weekly. Outcome did differ, however, dependant on the total number of treatments administered. Response was better in patients receiving 30 or more total treatments, as compared with fewer., Conclusions: Soft tissue radionecrosis of the gastrointestinal tract or bladder is (1) effectively treated with hyperbaric oxygen, (2) has a higher response rate if at least 30 treatments are administered, and (3) is equally responsive to rates of hyperbaric treatment ranging from 3 or fewer to 7 or more treatments per week.

Introduction: Robotic-assisted laparoscopic radical prostatectomy (RLRP) is playing an increasing role in the surgical management of prostate cancer. The benefits of minimally invasive surgery, enhanced surgeon familiarity with the instrumentation, and increased patient demand has led to the popularity of this surgical technique. There are, however, shortcomings specifically associated with this technology. Notably, instrumentation failure associated with robotic procedures represents a new and unique problem in urological surgery. We examine the rate of mechanical failure of the da Vinci robotic system and its impact on our prostate cancer program., Materials and Methods: We reviewed our prospective, institutional review board-approved database of the first 350 RLRP procedures that were scheduled for surgery at our institution. We identified all cases in which mechanical failure of the da Vinci robotic system resulted in surgery being cancelled, postponed, or converted to a conventional laparoscopic or an open radical prostatectomy., Results: Nine of the 350 (2.6%) scheduled RLRPs were unable to be completed robotically secondary to device malfunction. Six of the malfunctions were detected prior to anesthesia induction and surgery was rescheduled. Three other malfunctions occurred intraoperatively and were converted either to a conventional laparoscopic (1 case) or an open surgical approach (2 cases). The etiology of the malfunctions included the following: set-up joint malfunction (2), arm malfunction (2), power error (1), monocular monitor loss (1), camera malfunction (1), metal fatigue/ break of surgeon's console hand piece (1) and software incompatibility (1)., Conclusions: Although uncommon, malfunction of the da Vinci robotic system does occur and may lead to psychological, financial, and logistical burdens for patients, physicians, and hospitals. Patients should be carefully counseled preoperatively regarding the possibility of robotic mechanical failure.

Introduction: Accurate clinical staging is critical in guiding treatment for patients with prostate adenocarcinoma. Endorectal magnetic resonance imaging (MRI) has been advocated to improve staging accuracy. In order to assess the learning curve for endorectal MRI interpretation, we compared two cohorts of patients with high-risk prostate who underwent endorectal MRI at a center with limited prior exposure to this imaging modality., Materials and Methods: Data for all patients who received a preoperative endorectal MRI followed by radical prostatectomy were prospectively collected. MRI was performed in patients with a high level of suspicion for extracapsular disease based on biopsy Gleason score, prostate specific antigen level, and digital rectal examination or if the Memorial Sloan-Kettering nomogram predicted a greater than 30% likelihood of extracapsular disease. The MRI results of our first 40 patients (group 1) and our second 40 patients (group 2) were compared to assess for improvement., Results: Between October 2003 and September 2005, 80 patients underwent an endorectal MRI followed by radical prostatectomy. Mean age and median PSA were 58.4 (range 43 - 74) and 6.4 (range 0.048 -115.0), respectively. MRI findings were compared to the pathological findings from the radical prostatectomy specimen. Sensitivity, specificity, positive predictive value, and negative predictive value for detection of extracapsular disease were 31.3% versus 64.7%, 70.8% versus 78.3%, 41.7% versus 68.8%, and 60.7% versus 75.0%, respectively in group 1 versus group 2. The accuracy of MRI for detecting extracapsular extension was 52.5% in group 1 compared to 72.5% in group 2., Conclusions: In our series, endorectal MRI initially did not accurately predict tumor stage in patients with prostatic adenocarcinoma. With further experience, the accuracy of MRI substantially improved and approached the results from centers with significant experience in the interpretation of endorectal prostate MRI.

Purpose: Radiation proctitis is a common complication following external beam radiation therapy and brachytherapy for prostate cancer. While 95% percent of radiation induced proctitis is temporary and self-limiting, up to 5% of patients experience toxicities that are refractory to conservative management. Hyperbaric oxygen has a well-defined role in treating chronic wounds, osteomyelitis, hemorrhagic cystitis and necrotizing fasciitis. We reviewed our experience with hyperbaric oxygen therapy for radiation induced proctitis in patients undergoing radiation treatment for prostate cancer., Materials and Methods: From October 1998 to December 2003, 27 patients with radiation induced proctitis secondary to brachytherapy (4), external beam radiation therapy (16) or combined modality (7) for prostate cancer were treated with hyperbaric oxygen therapy at Virginia Mason Medical Center in Seattle, Washington. In all patients primary medical or endoscopic management had failed. Patients received 100% oxygen in a multiplace hyperbaric chamber at a pressure of 2.4 atmospheres absolute for 90 minutes 5 to 7 days weekly for an average of 36 sessions (range 29 to 60). Data were collected from a retrospective review of medical records following approval by the Institutional Review Board at Virginia Mason Medical Center., Results: All 27 men completed the planned course of therapy. Of patients with bleeding 48% showed complete resolution after therapy, while 28% reported significantly fewer bleeding episodes. Of patients 50% noted complete resolution of fecal urgency. Six of the 8 patients (75%) with pain noticed some improvement after therapy, although no patients reported complete resolution of rectal pain. Of patients with rectal ulceration 21% showed complete resolution of the ulcer on posttreatment endoscopy, while 29% showed evidence of improvement. Six patients (43%) had no change or worsening of rectal ulcers. Overall 67% of patients had a partial to good response, while 33% showed no response or disease progression., Conclusions: This series of patients showed a good overall response rate to hyperbaric oxygen for radiation induced proctopathy after other attempts at management had failed. Hyperbaric oxygen is generally well tolerated and it remains an important treatment option for managing this common and difficult disease.

Primary epididymal adenocarcinoma is a rare malignancy with fewer than 30 documented cases. We report a case of a 57-year-old patient with a paratesticular mass in the presence of retroperitoneal metastatic disease. Histology confirmed the presence of primary paratesticular adenocarcinoma. In this report we review the index case, the pertinent literature and discuss adjuvant therapy.

Objective: To evaluate taking more biopsy cores for predicting the radical prostatectomy (RP) Gleason score compared with the biopsy Gleason score, as although random sextant biopsies are the standard for a tissue diagnosis of prostate cancer, and taking more biopsies increases the detection rate, it is uncertain whether taking more cores improves the prediction of the RP Gleason score., Patients and Methods: We analysed retrospectively 404 patients from three centres (Seattle 162, Washington 107 and Chicago 135) who had RP for prostate cancer. Six, eight or 10 biopsies were taken based on the physician's preference and the patient's characteristics., Results: Before RP, 158 (39%) patients had six, 65 (16%) had eight and 181 (45%) had 10 biopsy cores taken. The accuracy of the Gleason sum of the three groups was 65/158 (41%), 26/65 (40%) and 104/181 (57.5%), respectively (P < 0.004, 10-core vs six-core). However, when comparing the Gleason score separately (i.e. 4 + 3 is not equal to 3 + 4), the accuracy of the three groups was 48/158 (30%), 20/65 (31%), and 95/181 (52.5%), respectively (P < 0.001, 10-core vs six core)., Conclusions: Taking more biopsy cores improves the accuracy of the biopsy Gleason score in predicting the final Gleason score at RP; the predictive accuracy of the final Gleason score may be increased from 41% to 58% by increasing the number of biopsies from six to 10.

Objectives: To assess the clinical factors that affect the efficacy of hyperbaric oxygen (HBO2) therapy in treating radiation-induced hemorrhagic cystitis. HBO2 therapy is an effective treatment for radiation-induced hemorrhagic cystitis, with reported response rates ranging from 76% to 100%., Methods: The data from patients with radiation-induced hemorrhagic cystitis treated at our institution between May 1988 and December 2001 were reviewed retrospectively. All patients received HBO2 therapy at 2.36 atm absolute pressure, with 90 minutes of 100% oxygen breathing per treatment. The outcome was assessed after at least 12 months of follow-up. We evaluated patient demographics, types of pelvic malignancy and radiotherapy, total radiation dose, onset and severity of hematuria, and prior intravesical management. Clinical improvement was defined as the absence of, or reduction in, macroscopic hematuria., Results: A total of 60 patients (55 men and 5 women), mean age 70 years, received an average of 33 HBO2 treatments (range 9 to 63). Of the 60 patients, 48 (80%) had either total or partial resolution of hematuria. When treated within 6 months of hematuria onset, 96% (27 of 28) had complete or partial symptomatic resolution (P = 0.003). All 11 patients with previous clot retention had clinical improvement if treated within 6 months of hematuria onset (P = 0.007). Prior intravesical chemical instillation did not affect the clinical outcome. Patients who had undergone primary, adjuvant, or salvage external beam pelvic radiotherapy showed response rates of 81%, 83%, and 78%, respectively (P = 0.950)., Conclusions: Our results show that delivery of HBO2 therapy within 6 months of hematuria onset is associated with a greater therapeutic response rate. Treatment efficacy was independent of prior intravesical therapy and the timing of radiotherapy.

Bilateral ureteral loss is an uncommon occurrence that challenges the usual reconstructive approaches. We developed a novel procedure, using autotransplantation of one kidney to bridge the ureteral deficit of the contralateral kidney. A 61-year-old woman developed long bilateral mid and distal ureteral strictures from idiopathic retroperitoneal fibrosis. The left kidney was autotransplanted to the right iliac fossa and the right ureter was anastomosed to the autotransplanted kidney's pelvis, followed by ureteroneocystostomy, all over a stent. This provided an intestine-free, physiologically normal system for draining both kidneys into the bladder. She had a stable creatinine of 1.7 mg/dL at 18 months postoperatively.

Objective: To assess the effects of hyperbaric oxygen (HBO2; often used to treat haemorrhagic cystitis, a known side-effect after radiation therapy for prostate cancer and with the potential to induce tumour angiogenesis and stimulate latent recurrence) on indolent in vivo prostate cancer in a murine model., Materials and Methods: Human prostate LNCaP cells were injected into 60 severe combined-immunodeficient mice; of these 24 (40%) did not develop palpable tumours after 6 weeks. They were randomized to undergo 20 sessions of either HBO2 or normobaric air in standardized conditions, and observed for another 4 weeks before the histological assessment of any palpable tumours that developed. Analysis of developed LNCaP tumours included tumour volume, microvessel density, MIB-1, p53, p27 and racemase staining intensity., Results: HBO2 was associated with less prostate tumour progression than normobaric air (P = 0.26). During HBO2 therapy, 10 mice remained free of palpable tumours, compared with seven controls (P = 0.30). On evaluation during the 4 weeks after therapy, six mice treated with HBO2 remained free of palpable tumours, vs eight of the controls (P = 0.17). There was tumour invasion and necrosis in a two of six and four of the HBO2 group during and after therapy, respectively, vs five and seven of the controls. Tumour microvessel density, proliferative index, differentiation and apoptosis markers were similar in both groups., Conclusions: HBO2 does not accelerate the growth of indolent prostate cancer in a murine model, suggesting that it does not increase the risk of residual prostate cancer reactivation when it is used to manage radiation-induced haemorrhagic cystitis in patients treated by pelvic radiotherapy for prostate cancer.

Purpose: We conducted a prospective cohort study to examine the relationship between bicycle characteristics and the occurrence of erectile dysfunction., Materials and Methods: Subjects consisted of 463 cyclists completing a cycling event of at least 320 km who were free of erectile dysfunction before their event., Results: The cumulative incidence of erectile dysfunction after the ride was 4.2% (95% confidence interval [CI] 2.4%-6.8%) and 1.8% (95% CI 0.7%-3.8%) 1 week and 1 month after the event, respectively. Bicycle characteristics associated with an increased risk of erectile dysfunction included a mountain bicycle compared with a road bicycle (risk ratio [RR] 4.1, 95% CI 1.6-12.5), and the relative height of the handlebars parallel with or higher than the saddle compared with the relative handlebar height lower than the saddle (RR 3.0, 95% CI 1.1-9.3). Perineal numbness during the ride was experienced by 31% of the cyclists and was associated with erectile dysfunction (RR 4.4, 95% CI 1.6-12.7). Saddle cutouts were associated with an increased risk of erectile dysfunction among those who experienced numbness (RR 6.0, 95% CI 1.3-27.1), but the association was reversed among those who did not report numbness (RR 0.3, 95% CI 0.0-2.5)., Conclusions: If the associations described are causal, then cyclists on a long-distance ride may be able to decrease the risk of erectile dysfunction by riding a road bicycle instead of a mountain bicycle, keeping handlebar height lower than saddle height and using a saddle without a cutout if perineal numbness is experienced.

Purpose: Hemorrhagic cystitis can occur 6 months to 10 years after pelvic radiation therapy with moderate to severe persistent rates of hematuria as 3% to 5% after radiotherapy for pelvic malignancies. Current treatment modalities for hemorrhagic cystitis include oral and intravenous agents, intravesical therapy and selective embolization of the hypogastric arteries. Hyperbaric oxygen therapy is now a widely accepted treatment option for radiation induced hemorrhagic cystitis. We assess the efficacy of hyperbaric oxygen for treatment of hemorrhagic cystitis., Material and Methods: From May 1988 through March 2001, 62 patients with radiation induced hemorrhagic cystitis were treated with hyperbaric oxygen at our institution. Followup ranged from 10 to 120 months. The primary pathological conditions were prostate cancer (81%) and bladder cancer (10%). Mean patient age was 70 years (range 15 to 88). Mean time between completion of radiation therapy and onset of hematuria was 48 months (range 0 to 355). Patients received an average of 33 hyperbaric oxygen treatments (range 9 to 68)., Results: Of the 62 patients treated information on 57 was available for analysis. Of the 57 patients (86%) 49 experienced complete resolution or marked improvement of hematuria following hyperbaric oxygen treatment. Of the 8 patients who did not improve 4 received fewer than 40 hyperbaric oxygen treatments and 7 prematurely terminated treatment (medical co-morbidities 4, claustrophobia 2, temporary resolution of symptoms 1)., Conclusions: Hyperbaric oxygen therapy for radiation induced hemorrhagic cystitis is an efficacious treatment modality for patients in whom other forms of management have failed.

Objective: To determine whether radical nephrectomy causes less morbidity, less mortality and is associated with a shorter hospital stay than is partial nephrectomy., Patients and Methods: A total of 1885 nephrectomies (1373 radical and 512 partial) conducted between 1991 and 1998 in the Department of Veterans Affairs (VA) National Surgical Quality Improvement Program were evaluated. Using multivariate analyses, outcomes were risk-adjusted based on 45 preoperative variables to compare mortality and morbidity rates., Results: The unadjusted 30-day mortality was 2.0% for radical and 1.6% for partial nephrectomy (P = 0.58). Risk-adjusting the two groups did not result in a statistically significant difference in mortality. The 30-day overall morbidity rate was 15% for radical and 16.2% for partial nephrectomy (P = 0.52); risk-adjusted morbidity rates were not statistically different. There were no statistically significant differences in the rates of postoperative progressive renal failure, acute renal failure, urinary tract infection, prolonged ileus, transfusion requirement, deep wound infection, or extended length of stay., Conclusions: Partial nephrectomy carried out in the VA program has low morbidity and mortality rates, comparable with the complication rates after radical nephrectomy.

Objective: To examine the outcome of 23 consecutive patients with Fournier's gangrene., Patients and Methods: Patients' charts were reviewed retrospectively from all those treated for Fournier's gangrene between July 1994 and July 1997 at the UCLA affiliated hospitals., Results: Twenty-three patients were identified (mean age 51.7 years, range 13-71). The aetiologies included perirectal abscess (43%), urethral stricture (30%), scrotal abscess (21%) and unknown (4%). Predisposing factors included diabetes mellitus (43%), steroids or chemotherapy (21%), alcohol abuse (43%), malignancy (26%) and radiation therapy (9%). All 23 patients initially received wide debridement and placement of a percutaneous suprapubic tube. At the time of the first surgery, total scrotectomy was required in all, colostomy in 17% and penectomy in 4%. An additional 35% required eventual colostomy and an additional 9% required a penectomy. Patients underwent repeat debridement a mean of 2.5 times; the overall survival was 96%., Conclusion: Survival can be improved in patients with Fournier's gangrene by combining aggressive surgical and medical management. The keys to successful outcome included a high index of suspicion, prompt fluid resuscitation, rapid initiation of broad-spectrum antibiotics, a multidisciplinary approach, early surgical intervention with radical debridement, haemodynamic support in an intensive care setting, and frequent repeat operative debridement.

It is now becoming accepted that one is not tolerant to all the determinants of self proteins: the T cell repertoire directed to some sequences in self proteins is intact and can be activated. When a self protein is exclusively expressed by tumour cells, the T cell repertoire directed to the particular self antigen can potentially be activated to attack the tumour: this would amount to induction of a beneficial autoimmune response. Prostate cancer offers a unique opportunity for activation of a tumour-specific immune response owing to the exclusive synthesis of prostate-specific antigen (PSA) and prostate-specific membrane antigen (PSM) by prostatic tissue and prostate tumour cells. In this study we examine the CD4 and CD8 T cell repertoires specific for peptides of PSA and PSM in normal human male individuals, using short-term, peptide antigen-driven CD4 and CD8 T cell lines. We show that short-term, CD4 T cell lines derived from six HLA-DR4 individuals showed strong proliferative responses to six of 10 tested peptides of PSA, selected as to contain a DR4 binding motif. Short-term, CD8 T cell lines from three HLA-A1 individuals showed specific cytolytic activity for autologous targets loaded with five of five tested peptides of PSA and PSM, selected to possess an HLA-A1 binding motif. One of the peptides chosen is termed a 'dual-motif' peptide, as it encodes determinants for both CD4 and CD8 T cells. These results, indicating the existence of CD4 and CD8 T cells against determinants of the self proteins, PSA and PSM, in healthy male individuals reveal the potential of the T cell repertoire from the typical prostate cancer patient to eradicate prostate tumours upon being appropriately activated.

Loop transverse colostomy is a procedure that has been traditionally employed on a temporary basis for a number of indications, but, with improvement of intestinal suturing and stapling techniques, the applicability of this modality has become quite limited. This paper addresses the issue of securing the loop and traces the history of the development of this method to decompress the bowel, to divert the fecal stream, and to defunctionalize the distal colon.