Prostate Bladder Research Articles

The association between allopurinol use and urologic malignancies: A nested case-control study.

435 Background: Oxidative stress may be involved in tumorigenesis processes. Uric acid is an important natural antioxidant that may reduce oxidative stress. Allopurinol is a commonly used uric acid lowering agent. There are conflicting data regarding the association between allopurinol use and cancer incidence. In the present nested case control study, we aimed to evaluated the association between allopurinol use and urologic malignancies in a large western population. Methods: conducted a nested case-control study within a population-representative database from the United Kingdom (THIN). Study cases were defined as individuals with any diagnostic code of prostate cancer, bladder cancer, or renal cell carcinoma. For every case, four eligible controls were matched on age, gender, practice site, time of diagnosis, and duration of follow-up. Exposure of interest was any allopurinol use prior to cancer diagnosis. Adjusted odds ratios (ORs) and 95% confidence intervals (CIs) for urologic malignancies were estimated using conditional logistic regression. Adjustment was performed for factors including smoking, BMI, and diabetes. Results: The study population included: for bladder cancer 13440 and 52421 matched controls, prostate cancer 27212 cases and 105940 controls, RCC 1547 cases and 6066 controls. Allopurinol use was associated with a significantly increase of risk for bladder cancer (adjusted OR 1.2, 95%CI 1.09-1.32, p<0.001). prostate cancer (adjusted OR 1.1, 95%CI 1.03-1.,17, p=0.003), RCC (adjusted OR 1.32, 95%CI 1-1..75, p=0.05). In a sensitivity analyses we observed similar associations when alopurinol use was initiated more than two years prior to cancer diagnosis, for bladder cancer (adjusted OR 1.2, 95%CI 1.08-1.33, p=0.001), prostate cancer (adjusted OR 1.09, 95%CI 1.02-1.16, p=0.01), RCC (adjusted OR 1.09, 95%CI 0.78-1.53, p=0.62). Conclusions: Allopurinol use may be associated with an increased risk for urologic malignancies.

Basic characteristics and features of the molecular genetic test systems designed for non-invasive diagnostics and prognosis of prostate cancer and bladder cancer

Improving the laboratory diagnosis of prostate cancer and bladder cancer are still an actual problem in modern urologic oncology. Test systems for DNA or RNA alterations that occurred during carcinogenesis and associated with the malignant tumor and the prognosis of disease have been actively developed in recent years. Here we reviewed the data published mainly in the last 5 years about the molecular genetic kits for diagnosis (Progensa, SelectMDx, ExoDx Prostate Test, Prosta-Test, Confirm MDx) and assessment of prognosis (Prolaris, Decipher, Oncotype DX) in patients with prostate cancer, discussed their sensitivity and specificity. The characteristics of analogous kits and panels for bladder cancer (UroVysion, CertNDx Bladder Cancer Assay, UroSEEK, mutations in the FGFR3 and TERT genes, and the Cxbladder Monitor/Detect/Triage kit's line) were systematized. Particularly we focused on the description of the patient cohorts for whom kits mentioned above have greater diagnostic accuracy, described limitations of these test systems in consequence both a methodological and registration aspects, and their use in combination with other tumor markers. This review is aimed at oncologists, urologists, laboratory geneticists and specialists in related professions.

Prostatic epithelial cells and their high expressions of CKIP-1 affect the TGF-\u03b21 expression levels which might reduce the scar formation in remodeling stage at prostatic urethral wounds after wound repair

ObjectiveThere are less scar formations in some wounds after wound repair. Our earlier study had shown that the amount of collagen fibers in canine prostatic urethra wound were less than in bladder neck wound after 2-μm laser resection of the prostate (TmLRP) and partial bladder neck mucosa at 4 weeks. The purpose of this study was to observe the amount of scar tissue and characterize the probable causes of “less scar healing” in prostatic urethra wound.MethodsA total of 12 healthy adult male crossbred canines underwent resection of prostate and partial bladder neck mucosa using 2-μm laser. The prostatic urethra and bladder neck wound specimens were harvested at 3, 4, 8 and 12 weeks after operation, respectively. The histopathologic characteristics were observed by hematoxylin and eosin(HE)staining, and the expression of transforming growth factor-β1 (TGF-β1) and casein kinase-2 interacting protein-1 (CKIP-1) were examined by immunohistochemistry in prostatic urethra and bladder neck wound, respectively. Overexpressed CKIP-1 human prostate epithelial cells (BPH-1 cells) were established and the expression of TGF-β1 was detected by Western blotting. Furthermore, a non-contact co-culture system of BPH-1 cells and human fibroblast (HFF-1) cells was used to observe the effects of BPH-1 cell and their high CKIP-1 levels on the expression of TGF-β1 in HFF-1 in vitro.ResultsThe histology showed that there were a large number of prostatic epithelium and a small amount of scar tissue in prostatic urethra wound, while no epithelial cells and more scar tissue in bladder neck wound at 4, 8 and 12 weeks after repair. There were a higher expression level of TGF-β1 in prostate epithelial cells and fibroblasts and a lower expression level of CKIP-1 in prostate epithelial cells at 3 weeks after surgery in prostatic urethral wound. Compared to week 3, the TGF-β1 expression decreased both in prostate epithelial cells and fibroblasts at 4, 8 and 12 weeks in prostatic urethral wound (p < 0.05 or p < 0.01). The CKIP-1 expression increased in prostate epithelial cells at 4, 8 and 12 weeks compared to 3 weeks in prostatic urethra wound (p < 0.01). A higher TGF-β1 expression level of fibroblasts was observed in bladder neck wound at 3 weeks. And there was no significant change in the expression of TGF-β1 of fibroblasts in 3, 4, 8 and 12 weeks after operation in bladder neck wound. Both the prostate urethra and bladder neck wound fibroblasts showed weak expression of CKIP-1 and there was no significant change in 3, 4, 8 and 12 weeks. The vitro experiments showed that the TGF-β1 expression in BPH-1 cells with CKIP-1 overexpression decreased 25% compared with control group (p < 0.05). Furthermore, the expression of TGF-β1 in HFF-1 cells of co-cultured group decreased by 20% compared with Control group (p < 0.05); the expression of TGF-β1 in HFF-1 cells of overexpression co-culture group were reduced by 15% compared with co-cultured group (p < 0.01).ConclusionsA large number of prostate epithelial cells in prostatic urethra wound may be one of the causes of less formation of scar tissue after repair. The prostate epithelial cells might reduce expression level of TGF-β1 by raising CKIP-1 expression and inhibit expression of TGF-β1 in peripheral fibroblasts at remodeling stage to reduce the excessive proliferation of fibrous cells and the excessive scar formation.

Palliative Radiation Therapy in patients with Oncology urological diseases: a component of complex treatment of Metastatic Bone Lesions

Background. Patients with first diagnosed prostate cancer, kidney cancer and bladder cancer, more than 25% of cases are diagnosed at stage IV disease at the primary visit in clinics. A characteristic feature of these types of tumors is a predisposition to bone metastasis. Bones failure at the treatment stages is diagnosed in 80% of patients already.Objectives. Determine the most effective palliative analgesic radiotherapy regimens.Materials and methods. Case histories of 41 patients with a diagnosis of osteolytic bone lesion were analyzed. The male / female ratio is 32/9. All patients underwent radiotherapy in the Radiological Division of the Rostov District Oncological Dispensary for the period from 2015 to 2018Results. The direct effectiveness of the analgesic effect of large-fraction radiotherapy is slightly higher than that of single-fraction radiotherapy. However, the opposite trend was observed a month after the R-therapy end. It was determined that higher analgesic effect corresponds to higher values of a single focal dose (SFD).Conclusion. This method deserves closer attention despite the low direct efficiency of single-fraction radiation. This is due to the high and persistent analgesic activity and the short duration of the course

Persistent storage symptoms after TURP can be predicted with a nomogram derived from the ice water test

To predict the persistence of storage symptoms after transurethral resection of the prostate (TURP) using a nomogram derived from the ice water test (IWT). The IWTs of 73 men with lower urinary tract symptoms and prostatic bladder outlet obstruction were retrospectively analyzed. The strength of the detrusor contraction was approximated by using the detrusor gradient of Δpdet /Δt at maximum detrusor pressure and the area under the curve. The parameters were utilized in a nomogram, which facilitated a severity categorization from 1 to 10. Patients with a positive IWT in the categories 1 to 2 were assigned to group A, categories 3 to 4 to group B and categories 5 and higher to group C. After TURP, patients with persisting storage symptoms were offered a botulinum toxin injection. There were 32 patients (44%) with negative and 41 patients (56%) with positive IWTs. Patients with negative IWTs were classified in category 1. Regarding patients with positive IWTs, 14 (34%) were correlated to group A, 14 (34%) to group B, and 13 (32%) to group C. The necessity of a subsequent botulinum toxin injection correlated significantly with a higher nomogram category (P < .001) as well as higher severity categorization (P < .001). In multivariate analysis, the nomogram category was an independent predictor for botulinum toxin injection (P = .002, OR, 6.9, CI, 2.0-23.9). The quantification of the detrusor contraction during the IWT allowed stratification of patients in risk categories for persistent storage symptoms after TURP and the potential need for later botulinum toxin injections.

Outcomes of Bladder Preservation Following Treatment for Rhabdomyosarcoma

Genitourinary rhabdomyosarcoma (RMS) is a relatively uncommon pediatric urologic oncologic condition with significant implications for both short- and long-term bladder functions. It is important for both pediatric and adult urologists to be aware of the pathophysiology, treatment, and long-term prognosis of this tumor and its potential impact on bladder function in both pediatric and adult survivors. Abnormalities in bladder function may arise secondary to surgical or medical management. Typical presenting complaints include lower urinary tract symptoms, which may be more common in pediatric RMS survivors than in survivors of other childhood cancers. Post-treatment evaluation of urinary function should include a baseline urodynamics study and an assessment of symptom severity and bother using validated, age-appropriate questionnaires. Upper tract monitoring should include renal/bladder ultrasound and serum creatinine. Hemorrhagic cystitis, which often develops acutely in patients receiving alkylating agents, may also present as a late effect. Lastly, urinary diversion may be required in patients with bladder/prostate (BP)-RMS either due to initial or delayed cystectomy or due to radiation-related loss of bladder function. Recent data suggest that diversion can maintain excellent quality of life in these patients. Both BP-RMS and its treatments have the potential for profound impacts on long-term bladder function. Most BP-RMS patients will survive beyond their initial diagnosis and treatment, and it is therefore important for both pediatric and adult urologists to be aware of the pathophysiology, treatment, and long-term prognosis of this tumor and its potential impact on bladder function in both pediatric and adult survivors.

Clinical value of suprapubic Trocar puncture lithotripsy in the treatment of benign prostatic hyperplasia and bladder stones

Objective To evaluate the clinical value of suprapubic Trocar puncture lithotripsy in the treatment of benign prostatic hyperplasia and bladder stones. Methods From February 2016 to August 2018, 60 patients with benign prostatic hyperplasia and bladder stones in the Second Hospital of Pujiang County were randomly selected.The patients were divided into transurethral prostatic bipolarplasma electrotomy group(control group, 30 cases) and transurethral prostatic bipolar excision procedure combined with suprapubic Trocar puncture cystinolithotomy group(study group, 30 cases) according to the operation methods.The operation time, stone extraction time, removal of bladder fistula time, catheter extraction time, success of one stone extraction, postoperative complications of the two groups were statistically analyzed. Results The operation time, stone removal time, bladder fistula removal time and catheter removal time of the study group were significantly shorter than those of the control group(t=6.965, 4.541, 3.365, 3.306, all P<0.05). The success rate of the first stone extraction in the study group was 100.0%(30/30), which was significantly higher than 86.7%(26/30) in the control group (χ2=12.83, P<0.05). The incidence rate of postoperative complications in the study group was 10.0%(3/30), which was significantly lower than 23.3%(7/30) in the control group(χ2=13.34, P<0.05). Conclusion Suprapubic Trocar puncture lithotripsy has high value in the treatment of benign prostatic hyperplasia and bladder stones. Key words: Urinary bladder calculi; Prostatic hyperplasia; Transurethral resection of prostate; Cystostomy; Cystotomy; Postoperative complications

Abstract B114: Cancer immunotherapy combining oral vaccination of recombinant Bifidobacterium longum displaying human Wilms’ tumor 1 protein and anti-PD-1 checkpoint blockade for solid tumors in mice experimental model

Abstract Nowadays, cancer immunotherapies such as immune-checkpoint inhibitors, chimeric antigen receptor T-cells and cancer vaccines have achieved great success in cancer therapy. Nevertheless, increasing cancer antigen-specific immune responses is necessary to obtain significant therapeutic effect. Recently, we had developed an oral cancer vaccine utilizing recombinant Bifidobacterium longum displaying murine Wilms’ tumor 1 antigen (B. longum 420) and had showed significant antitumor effect against WT1-positive leukemic cells by induction of WT1-specifc cytotoxic T-cell (CTL)-mediated immunity via activation of gut mucosal immune system in mice. In this study, we constructed B. longum displaying modified-human WT1 (B. longum 440) and investigated the antitumor effect against solid tumors in mice experimental model. Wild-type B. longum 105-A strain was transformed by electroporation by E. coli-B. longum shuttle vector and recombinant B. longum 440 was constructed. B. longum 440 was displaying human WT1 protein that had modified human WT1-CTL epitope to increase the affinity for MHC-class I. 1×106 of TRAMP-C2, a murine prostate cancer, MBT-2, a murine bladder cancer, and 3LL, a murine lung cancer cell lines were subcutaneously inoculated into mice respectively. All the cell lines were endogenously expressing WT1 protein. After tumor formation, 1×109 of B. longum 440, B. longum 2012 (negative control), or PBS were orally administered 5 times a week for following weeks. PD1-antibody therapy was combined with B. longum 440 therapy to investigate synergistic antitumor effect of immune checkpoint inhibitor against MBT-2. We also performed in vitro co-culture experiments by using B. longum 440, human dendritic cells (DCs) and CTLs derived from human peripheral blood mononuclear cells (PBMCs) to investigate the immune-interaction between B. longum 440 and human immune cells responsible for WT1-spcific immunity. As the results, oral vaccination of B. longum 440 induced significantly higher antitumor effect against TRAMP-C2 and 3LL compared with other therapies, and significantly prolonged overall survival (p&amp;lt;0.05). The combination therapy of B. longum 440 and anti-PD-1 induced substantially higher antitumor effect against MBT-2 tumor than B. longum 440 or PD-1 single therapy, and 40% of the mice completely suppressed the tumor growth. Significantly higher WT1-CTL-epitope, Db126 and mp235-specific IFN-γ and IL-2 production in CD4 and CD8 T-cells were seen in spleen cells isolated from B. longum 440-immunized mice, suggesting that human B. longum 440 could induce WT1-specific T-cell responses in mice as well as murine B. longum 420 as previously reported. Regarding in vitro assay, after co-culturing of B. longum 440 and human DCs, matured DCs that ingested WT1 protein were successfully induced. Then, WT1-specific CTLs were induced by co-culturing of the matured DCs and suspended PBMCs in vitro. As the results, those WT1-specific CTLs elicited significantly higher cell cytotoxicity against A549, a human non-small lung cancer cell line, and T24, a grade 3 human bladder cancer cell line compared to control B. longum 2012 (p&amp;lt;0.05), supporting that B. longum 440 might induce functional WT1-specific CTLs in human. In conclusion, we demonstrated that oral cancer vaccination by using B. longum 440 could induced antitumor effect against prostate cancer, lung cancer and bladder cancer in mice experimental model. In addition, we showed the synergistic antitumor effect of combination therapy of anti-PD-1 and B. longum 440 against bladder cancer. Our findings from in vitro co-culture experiments also supported that combining B. longum 440 cancer vaccines with checkpoint inhibitors has the potential to mediate tumor regression in human. Therefore, B. longum could be a promising candidate of combination immunotherapy with immune checkpoint inhibitors including pembrolizumab, an anti-PD-1 antibody therapy for treatment of advanced bladder cancer. Citation Format: Koichi Kitagawa, Maho Tatsumi, Mako Kato, Shota Komai, Yoshiko Hashii, Takane Katayama, Toshiro Shirakawa. Cancer immunotherapy combining oral vaccination of recombinant Bifidobacterium longum displaying human Wilms’ tumor 1 protein and anti-PD-1 checkpoint blockade for solid tumors in mice experimental model [abstract]. In: Proceedings of the Fourth CRI-CIMT-EATI-AACR International Cancer Immunotherapy Conference: Translating Science into Survival; Sept 30-Oct 3, 2018; New York, NY. Philadelphia (PA): AACR; Cancer Immunol Res 2019;7(2 Suppl):Abstract nr B114.

Is loss of power output due to laser fiber degradation still an issue during prostate vaporization using the 180 W GreenLight XPS laser?

To investigate whether heat-induced fiber degradation and loss of power output, which occurred during GreenLight laser vaporization (LV) of the prostate using the first- and second-generation 80 and 120W laser, are still an issue during LV using the upgraded third generation 180W GreenLight XPS™ laser. Laser beam power output of 53 laser fibers was measured at baseline and after every 25kJ of delivered energy during routine 180W GreenLight XPS™ LV in 47 patients with prostatic bladder outflow obstruction. After the procedures, the fiber tips were microscopically examined. The median applied energy per patient was 178kJ [interquartile range (IQR): 106-247]. Loss of power output during the procedure was detectable in all fibers. After the application of 25, 150, and 250kJ, the median power output decreased to 77% (IQR 59-87), 57% (IQR 32-71), and 51% (IQR 37-64) of the baseline value. Nine fibers (17%) remained on a relatively high power output level (> 80% of the initial output), while 13 fibers (25%) showed an end-of-procedure power output of less than 20%. Microscopy of the fiber tip revealed mild-to-moderate overall degradation and increasing degradation with higher energy delivered. Despite changes in fiber design, heat-induced fiber damage and loss of power output remain an issue during 180W GreenLight XPS™ LV. Whether modifications of the surgical technique can prevent impairment of fiber performance needs to be further evaluated.

The high-risk HPV infection and urinary system tumor

AbstractHPV is classified into high-risk and low-risk types depending on its probability of leading to tumorigenesis. Many studies have shown that HPV infection, especially the infection caused by the high-risk type, is always related to prostate cancer, bladder cancer, penile cancer, testicular cancer, and other urinary system tumors. However, previous studies differed in sexual openness and racial genetic susceptibility of the study object, sample size, and experimental methods. Hence, the correlation between high-risk HPV infection and urinary system tumors remains controversial. The early open reading frame of the HPV genome is composed of E1–E7, among which E6 and E7 are the key transfer proteins. The combination of these proteins with oncogene and anti-oncogene may be one of the mechanisms leading to tumorigenesis.

Combined prostatic urethral lift and remodeling of the prostate and bladder neck: a modified transurethral approach in the treatment of symptomatic lower urinary tract obstruction.

The aim of the study was to evaluate the feasibility and safety of combining prostatic urethral lift (PUL) and a limited resection of the prostatic middle lobe or bladder neck incision in the treatment of lower urinary tract symptoms (LUTS) secondary to benign prostatic hyperplasia (BPH). Twenty-eight patients were treated at two tertiary centers and followed prospectively. Patient evaluations included patient characteristics, relief of LUTS symptoms, erectile and ejaculatory function, continence, operative time and adverse events. Patients were followed for a mean of 10.9months. Patient characteristics were as follows: age 66years (46-85), prostate volume 39.6cc (22-66), preoperative IPSS/AUASI 20 (6-35)/QoL 3.9 (1-6)/peak flow 10.5mL/s (4.0-19)/post-void residual volume (PVR) 123mL (0-500). Mean operating time was 31min (9-55). Postoperative complications were minor except for the surgical retreatment of one patient for blood clot retention (Clavien 3b). One patient required catheterization due to urinary retention. Reduction of symptoms (IPSS -59.6%), increase in QoL (+49.0%), increase in flow (+111.5%), and reduction of PVR (-66.8%) were significant. Antegrade ejaculation was always maintained. Our data suggest that a combination of PUL and transurethral surgical techniques is feasible, safe, and effective. This approach may be offered to patients with moderate size prostates including those with unfavorable anatomic conditions for PUL. This procedure is still 'minimally invasive' and preserves sexual function. In addition, it may add to a higher functional efficacy compared to PUL alone. DRKS00008970.

Analysis of clinical efficacy of transurethral plasmakinetic resection of prostate combined with pneumatic lithotripsy in the treatment of benign prostatic hyperplasia and bladder stones

Objective To analyse the clinical efficacy and adverse reactions of transurethral plasmakinetic resection of prostate(PKRP) combined with pneumatic lithotripsy(TULT) in the treatment of benign prostatic hyperplasia(BPH) and bladder stones. Methods 78 cases with BPH and bladder stones were selected as the study subjects, and they were randomly divided into two groups, 39 cases in each group. They were all treated with transurethral PKRP, on this basis, patients in the control group were treated with small incision incision, patients in the observation group were treated with TULT. The clinical effect and complications were analyzed. Results The gravel time of the observation group was (28.56±4.73)min, which was significantly shorter than that of the control group. The intraoperative blood loss in the observation group was (103.47±10.58)mL, which was significantly less than that of the control group, there were statistically significant differences between the two groups(t=6.44, 6.85, all P 0.05). The postoperative catheterization time, bladder irrigation time and hospitalization time in the observation group were (5.26±1.38)d, (1.27±0.84)d and (6.34±1.25)d, respectively, which were significantly shorter than those in the control group, the differences were statistically significant(t=7.84, 7.16, 8.01, all P 0.05). The incidence rate of complications of the observation group was 2.56%, which was significantly lower than 5.13% of the control group(χ2=2.36, P>0.05). Conclusion The clinical efficacy and adverse reactions of transurethral PKRP combined with TULT in the treatment of BPH and bladder stones has significant effect, the utility model has the advantages of simple operation, small trauma, quick recovery and less complications, it can be used as the first choice for the treatment of elderly patients with BPH and bladder stones. Key words: Prostatic hyperplasia; Transurethral resection of prostate; Lithotripsy; Urinary bladder calculi

Transurethral plasmakinetic enucleation of prostate and suprapubic small cut in the treatment of patients with moderate and severe benign prostatic hyperplasia and multiple bladder stones

Objective To discuss the safety and efficiency of transurethral plasmakinetic enucleation of prostate and suprapubic small cut in the treatment of patients with moderate and severe benign prostatic hyperplasia and multiple bladder stones. Methods A total of 18 patients with moderate and severe benign prostatic hyperplasia and multiple bladder stones underwent plasmakinetic enucleation. Enucleation of the prostate was pushed into the bladder. We made a small suprapubic incision (3~4 cm) to remove prostate tissue and bladder stones completely. Results All operations of the 18 patients were successful. The weight of prostate tissue was 65~256 g, with an average of 87.6 g. Bladder stones were 3~21, with an average of 6.3. The mean operative time of prostate enucleation was 20~40 min. The time of removing the gland and bladder stones was 15~30 min. The volume of blood loss during operation was 50~100 mL. The postoperative time of wash the bladder continuously was 24~28 hours. The urethral catheters were removed after 4~5 days. Temporary incontinence occurred in one patient, but it disappeared after mention anal training 5 days later. All the 18 cases were followed up from 2 to 34 months, with an average of 19.8 months. There was no blood and all had good urination. International Prostate Symptom Scores (IPSS) one month after operation decreased from 25.6 to 7.4. The mean volume of Qmax increased from 6.3 mL/s before operation to postoperative 17.6 mL/s. Conclusions Transurethral plasmakinetic enucleation of prostate and suprapubic small cut in the treatment of patients with moderate and severe benign prostatic hyperplasia and multi-ple bladder stones is safe and effective. With simple operation and fewer complications, it should be applied more widely for patients. Key words: Prostatic Hyperplasia; Urinary Bladder Calculi; Prostatectomy

Current Treatment of Pediatric Bladder and Prostate Rhabdomyosarcoma.

Rhabdomyosarcoma (RMS) is the most common sarcoma diagnosed in the first 20years of life; bladder/prostate (BP) RMS accounts for 5% of all cases. Through efforts from multiple cooperative study groups, survival has improved significantly. This article aims to review the complex RMS classification system and treatment of BP RMS, with a focus on developing aspects of treatment. Recent advancements in technology are responsible for most of the progress in RMS treatment. PET-CT scanning has been shown to be superior to conventional metastatic workup. The use of proton beam therapy and brachytherapy to reduce the side effects of radiation is also showing promise. All cooperative oncology groups agree on surgical biopsy for diagnosis and staging of BP RMS. Patients are then grouped and risk classified before receiving chemotherapy. Regardless of local control strategy, oncologic outcomes appear to be similar for BP RMS. Alternative treatment strategies, which remain unproven, include brachytherapy and proton therapy.

Pulsed-dose rate brachytherapy for pediatric bladder prostate rhabdomyosarcoma: Compliance and early clinical results

ObjectiveNo data are available on the feasibility of pulsed dose rate (PDR) brachytherapy in very young children. Our experience of PDR brachytherapy for bladder prostate (BP) rhabdomyosarcoma (RMS) is reported, with focus on compliance and dosimetric parameters. Materials and methodsTreatment parameters and outcome of consecutive BP RMS patients treated in our center were examined. Treatment was carried out as part of a multimodal conservative radio-surgical treatment. Four single leader plastic tubes were implanted under perioperative guidance, encompassing the prostate/bladder neck. Tubes were systematically sutured to the bladder wall. Treatment planning was based on a computed tomography and followed Paris system rules. Continuous hourly pulses of 0.42Gy were delivered, to a total dose of 60Gy. Results32 patients were treated, median age 2.6years (10months–12years). Median duration of each pulse was 8.5min (3.8–17.4min). The minimal dose in the most irradiated 1cm3 of rectum was 44.7Gyα/β=3 (range: 4.1–77.3Gyα/β=3). Brachytherapy was conducted without significant compliance concern in all but two patients, 24 and 25months-old, who pulled out plastic tubes before treatment completion. Another child needed re-planning because of slight tube displacement. With median follow-up of 14.4months (15days–75months), all patients were free from any relapse after local treatment. Four grade 3 acute urinary complications were encountered. All long-term side effects were grade 2 or less. ConclusionPDR brachytherapy is feasible in very young patients, and associated with acceptable acute toxicity rates. Longer follow-up is required to ensure that local control and long-term side effects profile are comparable to the results of low dose rate brachytherapy.

Abstract 2014: Genitourinary cancer-derived cells produce microenvironment proteinases that regulate proteinase activated receptors (PARs) to drive oncogenic signaling

Abstract Background: Thrombin-triggered activation of proteinase-activated receptor-1 (PAR1) is recognized as a key stimulus for driving epithelial malignancies (IUBMB life.63:397, 2011; PMID:21557443). However, the enzymes for regulating PAR1 in the tumour microenvironment are not known. Hypothesis: We hypothesize that prostate (PC) and urinary bladder cancer (UBC) cells can regulate microenvironment signaling to drive cancer progression via the secretion of proteinases that cleave/regulate proteinase-activated receptors (PARs). Aims: 1.) Visualize the cleavage status of N- and C-terminally-dual-labelled PARs in receptor-transfected UBC- and PC-derived cells. 2.) Measure PAR cleavage by UBC and PC-secreted proteinases. 3.) Identify the UBC &amp; PC-derived proteinases that cleave/regulate PAR function. Methods: The cleavage status of dual-labeled PARs (N-terminus-mCherry/C-terminus-YFP) expressed in PC &amp; UBC cells was determined by confocal image analysis as already described (JBC 288:32979, 2013; PMID: 26957205). Intact receptors look 'yellow' and cleaved receptors look 'green'. The cleavage of PARs in UBC and PC cells was studied for dual-tagged-PAR-expressing UBC and PC cells exposed or not to cell-derived culture supernatants, enzyme agonists for PAR1 and 2 (thrombin and trypsin, respectively), and proteinase inhibitors (e.g. for MMPs and other enzymes). The impact of CRISPR-mediated elimination of MMPs from PC3 cells on PAR1 cleavage status was also monitored. Results: UBC- and PC-produced enzymes can cleave PAR1 as efficiently as thrombin, an established PAR1 agonist. None of the UBC cell lines produce proteinases that cleave PAR2. Inhibition of MMP activity partially prevents PAR1 cleavage by UBC cells and completely prevents PAR1 cleavage in PC3-PC cells. Conclusions: We conclude that UBC and PC cells secrete PAR-regulating proteinases that can directly regulate PAR1 in the tumour microenvironment so as to drive cancer progression. Funding: Alberta Innovates CRIO Grant, Prostate Cancer Canada Discovery Grant, Motorcycle Ride for Dad, Johnson &amp; Johnson Alberta Health Partnership and CIHR Note: This abstract was not presented at the meeting. Citation Format: Stacy G. Gibson, Koichiro Mihara, Andries Zijlstra, Matthew E. Hyndman, Morley D. Hollenberg. Genitourinary cancer-derived cells produce microenvironment proteinases that regulate proteinase activated receptors (PARs) to drive oncogenic signaling [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 2014. doi:10.1158/1538-7445.AM2017-2014

V1-10 IS CONTINENCE POSSIBLE IN PATIENTS WITH DOUBLE BLOCK AT BLADDER NECK -PROSTATE AND MEMBRANO -BULBAR URETHRA AFTER PELVIC FRACTURE URETHRAL INJURY?

You have accessJournal of UrologyReconstruction Lower Tract (I)1 Apr 2017V1-10 IS CONTINENCE POSSIBLE IN PATIENTS WITH DOUBLE BLOCK AT BLADDER NECK -PROSTATE AND MEMBRANO -BULBAR URETHRA AFTER PELVIC FRACTURE URETHRAL INJURY? Pankaj Joshi, Devang Desai, Sandesh Surana, Hazem Orabi, Craig Hunter, and Sanjay Kulkarni Pankaj JoshiPankaj Joshi More articles by this author , Devang DesaiDevang Desai More articles by this author , Sandesh SuranaSandesh Surana More articles by this author , Hazem OrabiHazem Orabi More articles by this author , Craig HunterCraig Hunter More articles by this author , and Sanjay KulkarniSanjay Kulkarni More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2017.02.242AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Rarely, pelvic fracture urethral injury can cause simultaneous transection of bladder neck and membrano-bulbar junction. Mundy reported sequestration of prostate. In another report, they found 85% of patients of PFUI have functioning external urethral sphincter mechanism after successful anastomotic repair. This information helped in our development of a new technique for repair in such cases to preserve continence. METHODS We present a retrospective review of 8 patients .Preoperative evaluation requires MCU and RGU. Urethroscopy evaluates the membrano-bulbar obliteration. Antegrade cystoscopy confirms the bladder neck obliteration. Pelvic MRI is also obtained to check for the prostate. Perineal incision- bulbar urethra is mobilized and transected proximally. Suprapubic incision- posterior pubectomy is performed. An endoscope passed through SPC tract and blocked bladder neck area is opened from outside. Semen collected in the sequestrated prostatic urethra is aspirated with needle over which prostatic urethra is opened .A 6Fr endoscope is passed through the prostatic urethra distally to visualize the membranous urethra. The membranous urethra is opened perfectly under vision as distally as possible. Excision of the scar at the apex of membranous urethra is kept to minimum to preserve continence. Bulbo-Membranous Anastomosis (BMA) and bladder neck–prostatic anastomosis is performed . RESULTS Mean age 14 (5 to 36) yrs ,mean follow up 26 (14 to 72) months .Initial 2 adults are 100% incontinent . We then modified our technique of identifying membranous urethra through intraprostatic scopy and bulbo membranous anastomosis. The video is of an adult who underwent transpubic urethroplasty at age 7 for double block. As prostatic urethra was rudimentary bulbo vesical anastomosis was performed. He presented at age 18 years with pain after ejaculation. He was reoperated using our modified technique.1 adult and all 5 children were approached through the above improved technique. 2 (40%) children required redo surgery with for revision of the bladder neck anastomosis. as we had tried narrow anastomosis to help continence. All children are continent and have good flow, 2 have occasional nocturnal dribbling. CONCLUSIONS Double transection with injury at membrano-bulbar and prostate bladder neck junction requires two separate anastomoses to be performed. Postoperative continence is possible .Our step wise technique improved continence rates to ensure proper preservation of the external sphincter. © 2017FiguresReferencesRelatedDetails Volume 197Issue 4SApril 2017Page: e70-e71 Advertisement Copyright & Permissions© 2017MetricsAuthor Information Pankaj Joshi More articles by this author Devang Desai More articles by this author Sandesh Surana More articles by this author Hazem Orabi More articles by this author Craig Hunter More articles by this author Sanjay Kulkarni More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...

The effective tool for self-assessment of adherence to treatment in patients with benign prostatic obstruction and overactive bladder symptoms

Purpose: Study of validity of the Medication Adherence Self-Report Inventory (MASRI) for use in clinical practice to treat patients with benign prostatic obstruction (BPO) accompanied with overactive bladder (OAB) symptoms.Methods: During 12 weeks of the randomized study, 452 patients with BPO and OAB symptoms (mean age of 61.3 (12.7)) were studied for adherence to the treatment with Tamsulosin, Solifenacin and Trospium using the MASRI. External monitoring instruments included the Brief Medication Questionnaire (BMQ) and the visual remaining pill count. The state of the prostate gland and the lower urinary tract was monitored using questionnaires I-PSS, OAB Awareness Tool, uroflowmetry and voiding diaries.Result: Correlation between the percentage of men non-adherent to treatment (MASRI) and the percentage of patients having a belief barrier on the screen of the BMQ was r = 0.89, p ≤0.05, r = 0.92, p ≤0.01, r = 0.85, p ≤0.05, a number of missed doses on the Regimen Screen of the BMQ was r = 0.79; p ≤0.05; r = 0.81; p ≤0.05; r = 0.75, p ≤0.05, a number of non-adherent patients according to the BMQ was r = 0.83 (p ≤0.05), r = 0.88 (p ≤0.05), r = 0.79, p ≤0.05, the results of the pill count were r = 0.65–0.76; p ≤0.05-0.01. These data confirm high validity of the MASRI.Conclusion: The MASRI is a valid tool for rapid assessment of adherence to treatment of patients with BPO and OAB receiving Tamsulosin and antimuscarinic drugs and may be recommended for use in clinical practice.

Progress in urinary protein tumor markers

The development of proteomic technique has sparked new focus on novel protein markers for many diseases including cancer. Urine is one of the most useful biofluids for routine testing to provide an ideal resource for the discovery of novel biomarkers, with the advantage over tissue biopsy samples due to the ease and the less invasive nature of urinary collection. This review summarizes urinary protein tumor markers found in prostate cancer, bladder cancer, lung cancer and breast cancer that have shown potential for urogenital and non-urogenital cancer, so as to provide reference on high sensitive and high specific urinary protein tumor markers for early prevention, early diagnosis and treatment of cancer. Key words: Urinary protein; Tumor markers; Early diagnosis

Abstract PR15: MYC distal enhancers underlie ovarian cancer susceptibility in the 8q24.21 locus.

Abstract Background: In a Genome Wide Association Study (GWAS) on epithelial ovarian cancer (EOC), we identified single nucleotide polymorphism (SNP) associations (p&amp;lt;10-8) in the 8q24.21 region. This region is characterized as a gene desert, which notably is also associated with other cancer types including prostate, colorectal, breast and urinary bladder cancer. We hypothesized that SNPs in this region function within enhancer elements that modify transcriptional regulation of a distant gene involved in ovarian cancer pathogenesis. Methods: Guided by fine mapping analysis of the locus, we employed various methods to select functional SNPs with allele-specific effects in ovarian surface epithelial (OSE) and fallopian tube epithelial (FTE) cells, based on the hypothesis that both cell types may represent the cell of origin for high-grade serous ovarian cancer. Luciferase assays tested the ability of enhancer elements to activate transcription. Chromosome conformation capture (3C) assays quantified the physical interactions between putative enhancer elements and candidate target genes. Electrophoretic mobility shift assays (EMSA) and proteomics analysis were utilized to confirm transcription factor binding. Results: We identified eight putative causal SNPs, which are in high Linkage Disequilibrium (LD) with the most significant SNP, rs1400482 (OR = 1.18, 95% CI 1.13 1.23; p = 2.5x10-13), residing within two distinct enhancer elements that display allele-specific activity in ovarian cells. Long-range physical interactions with the promoter region of the MYC oncogene, and to a lesser extent, the non-coding RNA, PVT1, establish these two genes as the targets of the enhancer elements containing the putative causal SNPs. We report evidence that the ATF1 transcription factor binds exclusively to the minor allele of variant rs2165806. Additionally, we report a comparative analysis testing the cell-type specific activity of different enhancer regions in breast, prostate, colorectal and ovarian cell lines. Conclusion: In summary, this work highlights the regulatory landscape of the 8q24.21 locus and provides a mechanistic basis to understand susceptibility to ovarian cancer in this region. Citation Format: Anxhela Gjyshi, Gustavo Mendoza-Fandino, Nicholas Woods, Jonathan Tyrer, Kate Lawrenson, Melissa Buckley, Howard Shen, Renato Carvalho, Ji-Heui Seo, Catherine Phelan, Matthew Freedman, Ellen Goode, Thomas Sellers, Simon Gayther, Paul Pharoah, Alvaro Monteiro. MYC distal enhancers underlie ovarian cancer susceptibility in the 8q24.21 locus. [abstract]. In: Proceedings of the AACR Special Conference on Advances in Ovarian Cancer Research: Exploiting Vulnerabilities; Oct 17-20, 2015; Orlando, FL. Philadelphia (PA): AACR; Clin Cancer Res 2016;22(2 Suppl):Abstract nr PR15.