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Background: Active surveillance (AS) aims to reduce overtreatment of low-risk prostate cancer (PC). Incorporating multiparametric magnetic resonance imaging (mp-MRI) and MR-guided biopsy (MRGB) in an AS protocol might contribute to more accurate identification of AS candidates. Objective: To evaluate the value of 3. T mp-MRI and MRGB in PC patients on AS at inclusion and after 12-mo follow-up. Design, setting, and participants: Patients with cT1c-cT2 PC, prostate-specific antigen (PSA) ≤10. ng/ml, PSA density 6, >2 positive cores at repeat transrectal ultrasound-guided biopsy (TRUSGB), presence of PC in >3 separate cancer foci upon both MRGB and TRUSGB, or cT3 tumor on mp-MRI. Outcome measurements and statistical analysis: Reclassification rates, treatment after discontinuation, and outcome on radical prostatectomy after discontinuing AS were reported. Uni- and multivariate analyses were performed to identify predictors of reclassification after 1 yr. Results and limitations: From 2009 to 2013, a total of 111 of 158 patients were consecutively and prospectively included. Around initial diagnosis, 36 patients were excluded from the study protocol; mp-MRI + MRGB reclassified 25/111 (23%) patients, and 11 patients were excluded at own request. Reasons for reclassification were as follows: GS upgrade (15/25, 60%); cT3 disease (3/25, 12%); suspicion of bone metastases (1/25, 4%); and multifocal disease upon MRGB (6/25, 24%). Repeat examinations after 1 yr showed reclassification in 33/75 patients (44%). Reasons were the following: GS upgrade upon TRUSGB (9/33, 27%); volume progression upon TRUSGB (9/33, 27%); cT3 disease upon mp-MRI (1/33, 3%); GS upgrade upon MRGB (1/33, 3%); volume progression upon MRGB (1/33, 3%); multifocal disease upon MRGB (2/33, 6%); and upgrade or upstage upon both TRUSGB and MRGB (10/33, 30%). On logistic regression analysis, the presence of cancer at initial mp-MRI and MRGB examinations was the only predictor of reclassification after 1 yr (odds ratio 5.9, 95% confidence interval 2.0-17.6). Conclusions: Although mp-MRI and MRGB are of additional value in the evaluation of PC patients on AS, the value of mp-MRI after 1 yr was limited. As a considerable percentage of GS ≥7 PC after 1 yr was detected only by TRUSGB, TRUSGB cannot be omitted yet. Patient summary: More aggressive tumors are detected if low-risk prostate cancer patients are additionally monitored by magnetic resonance imaging. However, some high-grade tumors are detected only by transrectal ultrasound-guided biopsy. Multiparametric magnetic resonance imaging (MRI) and MR-guided biopsies are of additional value in the initial evaluation of prostate cancer patients on active surveillance. At repeat examinations after 1 yr, transrectal ultrasound-guided biopsies cannot be omitted yet, as MRI could not detect all aggressive tumors.

Het doel van het ERAS-protocol is het postoperatieve herstel te optimaliseren. Om te inventariseren welke invulling landelijk gegeven wordt aan dit protocol, hebben wij een enquete gehouden onder Nederlandse urologen. Hieruit bleek dat er nog veel verschillen bestaan tussen de ziekenhuizen. Om het effect van ERAS te onderzoeken, hebben wij een onderzoek gedaan in onze eigen kliniek. In deze studie hebben wij de resultaten vergeleken van de robotgeassisteerde radicale cystectomie met intracorporele reconstructie (RARC-IC) voor en na de introductie van het ERAS-protocol. 37 patienten zijn geopereerd in de periode voor introductie van het protocol en 71 erna. Preoperatief waren er geen verschillen tussen beide groepen. De OK-tijd verminderde significant en de gemiddelde opnameduur daalde van 14 naar acht dagen. Het aantal complicaties nam niet toe. De afgenomen OK-tijd is te verklaren vanuit het doorlopen van de RARC-leercurve. Verder onderzoek moet aantonen hoe het ideale ERAS-protocol eruit moet zien en wat de meerwaarde is van een dergelijk protocol.

De open radicale cystectomie wordt beschouwd als de standaardbehandeling van het spierinvasief blaascarcinoom en bij recidiverend hoogrisico niet-spierinvasief blaascarcinoom. Sinds 2000 wordt de cystectomie steeds meer laparoscopisch en met assistentie van de robot uitgevoerd, al dan niet met een intracorporeel aangelegde urinedeviatie. De resultaten uit de literatuur komen vooral uit retrospectieve studies, waarin de resultaten worden vergeleken met historische open cystectomieseries. In combinatie met de resultaten van enkele kleinere prospectieve series is er aanzienlijk bewijs dat de robotgeassisteerde radicale cystectomie (RARC) een veilige techniek is waarbij minder bloedverlies en bloedtransfusiebehoefte optreedt en patiënten minder lang opgenomen zijn ten opzichte van de open radicale cystectomie (ORC). Ten aanzien van de functionele en oncologische resultaten lijkt de RARC niet onder te doen voor de ORC. Daarbij heeft de RARC een groot ergonomisch voordeel. Een nadeel is dat de aanschaf en het gebruik van een daVinci™-systeem gepaard gaan met hogere kosten.Zowel internationaal als nationaal wordt momenteel gewerkt aan prospectieve multicentrische vergelijkende studies om het mogelijke verschil aan te tonen ten opzichte van de ORC op het oncologische en/of functionele vlak, maar daarnaast meer duidelijkheid te verkrijgen ten aanzien van de kosteneffectiviteit van de RARC., The open radical cystectomy is considered the golden standard treatment for muscle invasive bladder cancer and recurrent high risk non-muscle invasive bladder cancer. Since 2000 there is an increase in the performance of laparoscopic and robotic assisted cystectomy with or without the creation of an intracorporal performed urine deviation. The results from literature mainly present retrospective studies reflecting comparison with historical open cystectomy series. In combination with few smaller prospective series there is ample evidence for RARC as a safe technique, accompanied with less blood loss and transfusion rates and shorter admission time, compared to the ORC. Concerning the functional and oncological results the RARC seems not inferior to the ORC. In addition, the RARC has a great ergonomic benefit. As a drawback the higher costs for purchase and use of the daVinci™ system can be mentioned. Nowadays, international and national studies are being developed to gain more evidence to show potential difference over the ORC as well as to clarify the concerns about the cost-effectiveness of the RARC.

Het doel van deze studie is evaluatie van de eerste ervaringen en perioperatieve complicaties met de robotgeassisteerde radicale cystectomie (RARC) en de intracorporele aanleg van de urinedeviatie volgens Bricker. 20 patienten ondergingen een RARC wegens een klinisch gelokaliseerd blaascarcinoom. Onderzocht zijn perien postoperatieve complicaties tot 30 dagen na de operatie, duur van de operatie, en het verloop en duur van de opname. De gemiddelde operatieduur was 377 (285-491) minuten, het bloedverlies bedroeg 202 (50-800) ml en de opnameduur was 15,3 (8-39) dagen. Er waren in totaal 11 (55%) chirurgische complicaties: 4 Clavien I-, 5 Clavien IIen 2 Clavien IIIb-complicaties. Er waren geen Clavien IV- of V-complicaties. Het is goed mogelijk om een RARC in een Nederlands perifeer ziekenhuis uit te voeren, inclusief de aanleg van de urinedeviatie volgens Bricker intracorporeel. Er is een duidelijk dalende trend in de operatieduur en het bloedverlies is gering.

Item does not contain fulltext OBJECTIVES: In muscle invasive bladder cancer (MIBC), careful clinical staging is essential for patient counseling and decision-making. Bimanual palpation (BP) is an integral part and guideline advice of clinical staging. Until now, however, the value of BP has never been studied. With this study, we aim to determine the accuracy of clinical staging through BP. METHODS: Detailed clinical data were collected from a population-based series of 1,409 patients with MIBC, diagnosed between 1989 and 2005, in the region of the Comprehensive Cancer Centre East in The Netherlands. Selected were all patients who underwent BP (n = 738). Preoperative tumor-stage (cT-stage) determined through BP was compared with post-cystectomy pT-stage. Contingency tables were made to determine the correlation between cT-stage and pT-stage. RESULTS: In 18 of 142 patients in whom BP showed an organ-confined tumor, the tumor was unresectable (pT4) at the time of surgery. Four out of 9 patients who had a suspected T4 tumor on BP but who underwent cystectomy anyway appeared to have operable tumors at cystectomy. In 87 patients (57.6%), accurate staging through BP was observed. In 17 patients (11.3%), clinical overstaging was found, and in 47 patients, (31.1%) clinical understaging. CONCLUSIONS: Frequently, pT-stage after cystectomy does not correlate with preoperative cT-stage based on BP. Discrepancy was observed in 42% of the patients: in 11%, clinical overstaging and in 31%, clinical understaging. Based on these data, some caution is suggested when interpreting the outcome of BP. Prospective data is needed for a more formal evaluation of the staging accuracy of BP.

Objectives. To evaluate microstaging by means of quantifying the depth of invasion of the subepithelial connective tissue in pT1 transitional cell carcinoma (TCC) of the bladder for its additional prognostic value with respect to disease recurrence and progression. Methods. We reviewed the pathologic findings of a consecutive series of 124 patients with pT1 tumors entered in a prospective randomized multicenter trial comparing mitomycin C and bacillus Calmette-Guerin treatment, with at least 3 years of follow-up and clinical outcome hidden from reviewers. The depth of invasion was established by identifying submucosal tumor invasion up to, in, or beyond the muscularis mucosae or vascular plexus and classified as pT1a, pT1b, or pT1c, respectively. In addition to tumor grade, the presence of carcinoma in situ (CIS) near the primary tumor or in biopsy specimens taken from abnormal looking mucosa was taken into account. The risks of recurrence and progression were calculated using Kaplan-Meier curves and modeled with proportional hazard models. Results. pT1 subclassification was possible in more than 90% of the specimens. The 3-year risk of recurrence was not different in any of the subgroups. By contrast, the Kaplan-Meier 3-year risk for progression was 6%, 33%, and 55% for pT1a, pT1b (hazard ratio [HR] 5.51), and pT1c (HR 12.35) tumors, respectively (log-rank test P < 0.001). The Kaplan-Meier 3-year risk of progression was 9% versus 39% (HR 5.62) for the absence or presence of CIS in the tumor (P = 0.001) and 8% versus 49% (HR 6.72) for CIS in biopsy specimens (P < 0.001). Tumor grade had no statistically significant prognostic value with respect to progression, nor had tumor volume or multifocality. The combination of the parameters (pT1c and CIS) increased the risk of progression by a factor of 27 (P < 0.0001) compared with the absence of pT1c and CIS. Conclusions. These data show that the extent of lamina propria invasion (pT1a, pT1b, pT1c) is a clinically relevant prognostic factor for progression of pT1 TCC of the bladder. With the combination of this pT1 subclassification and the presence of CIS subgroups, distinct risks of progression can be identified that may give additional information for follow-up and treatment policies.

There is accumulating evidence that some biochemical pathways observable by magnetic resonance spectroscopy, e.g., citrate acid and phospholipid metabolism, are altered in human prostate cancer. Four well-established human prostate cancer cell lines were therefore studied with magnetic resonance spectroscopy to compare differences in metabolic content with tumor biological behavior. Herein we demonstrate that, although each cell line has its own metabolic profile, relative creatine and citrate levels can be used to discriminate the androgen-dependent LNCaP cell line from the androgen-independent DU-145, TSU, and PC-3 cell lines.

Contains fulltext : 97259.pdf (Publisher’s version ) (Closed access) Prognostic factors for survival after recurrent MIBC are unknown and were evaluated using a population-based series of 1409 MIBC patients. 330 Patients who underwent RC or RT with curative intent and who suffered from recurrence were selected. Multivariable survival analyses were performed. Clinicopathological factors that predict survival after recurrence are recurrence location, treatment for recurrence and age at recurrence diagnosis. PURPOSE: We conducted this study to evaluate the prognostic factors for survival among patients with recurrent muscle-invasive bladder cancer (MIBC) after initial treatment with curative intent. PATIENTS AND METHODS: Clinical data were collected from a population-based series of 1409 patients with MIBC. We selected 330 patients who underwent radical cystectomy (RC) or radiotherapy (RT) for urothelial carcinoma with curative intent and who experienced recurrence. Multivariate survival analyses were performed with death from MIBC as the endpoint. Covariates were gender, time to recurrence, age at diagnosis of recurrence, recurrence multiplicity, localization, and treatment for recurrence. Analyses were performed separately for patients initially treated with RC (i-RC) or external beam radiotherapy (i-EBRT). RESULTS: Patients with recurrence after i-RC showed a 1- and 3-year survival of 17% and 6%, respectively. Localization and treatment for recurrence were significantly associated with survival. Patients with recurrence after i-EBRT showed a 1- and 3-year survival of 31% and 12%, respectively. Age at diagnosis of recurrence, localization, and treatment for recurrence were significantly associated with survival. CONCLUSION: This study confirms the extremely poor prognosis after recurrence of MIBC in patients initially treated with surgery or RT. Clinicopathologic factors that predict survival after disease recurrence are location of recurrence, treatment for recurrence, and age at diagnosis of recurrence. Improved diagnosis of primary MIBC to detect extravesical disease and more effective therapeutic approaches to target recurrent MIBC are needed.

Recently, we have shown that connecting live three-dimensional (3D) monitors to all three available Da Vinci® robot (Intuitive) generations improved the impression of shared perception for the whole surgical team. Standardized dry lab experiments revealed that delicate teamwork was faster (up to 40%) when using the 3D monitor [1]. We now studied whether introduction of 3D auxiliary monitor for the assistants at the operating table indeed had a positive impact for robot-assisted laparoscopic partial tumor-nephrectomies (RAL-PN). In order to exclude possible learning curve effects, we examined the data of 26 procedures of 1 experienced surgeon and team members where in every case the same standardized surgical procedure was performed.

Ondanks de inzet van de robot bij de radicale cystectomie (RARC) is er nog weinig bekend over de kosteneffectiviteit.

Contains fulltext : 81043.pdf (Publisher’s version ) (Closed access) OBJECTIVES: To study the time-to-recurrence and duration of response in non-muscle invasive bladder cancer (NMIBC) patients, with a complete ablative response after intravesical apaziquone instillations. METHODS: Transurethral resection of bladder tumour(s) (TURBT) was performed in patients with multiple pTa-T1 G1-2 urothelial cell carcinoma (UCC) of the bladder, with the exception of one marker lesion of 0.5-1.0 cm. Intravesical apaziquone was administered at weekly intervals for six consecutive weeks, without maintenance instillations. A histological confirmed response was obtained 2-4 weeks after the last instillation. Routine follow-up (FU) was carried out at 6, 9, 12, 18 and 24 months from the first apaziquone instillation. RESULTS: At 3 months FU 31 of 46 patients (67.4%) had a complete response (CR) to ablative treatment. Side-effects on the long-term were only mild. Two CR patients dropped out during FU. On intention-to-treat (ITT) analysis 49.5% of the CR patients were recurrence-free at 24 months FU, with a median duration of response of 18 months. Of 15 no response (NR) patients, only two received additional prophylactic instillations after TURBT. On ITT-analysis 26.7% of the NR patients were recurrence-free (log rank test, P = 0.155). The overall recurrence-free survival was 39% (18 of 46 patients) at 24 months FU. CONCLUSIONS: The CR of the marker lesion in 67% of patients was followed by a recurrence-free rate of 56.5% at 1-year FU, and 49.5% at 2-year FU. These long-term results are good in comparison with the results of other ablative studies.

In this study, it was investigated whether prostate tumor biological parameters correlate with metabolic profiles. 1H and 31P magnetic resonance spectra were acquired from perchloric acid extracts of seven Dunning R-3327 prostate tumor sublines. Several metabolic ratios, for example, phosphocholine/total phosphate, choline/total creatine, and inositol/total creatine, did not correlate specifically with one biological characteristic but, based on each of these ratios, the well-differentiated, nonmetastatic, and hormone-dependent sublines could be discriminated from the poorly differentiated or anaplastic, metastatic, and hormone-independent sublines. The glycerophosphoethanolamine/total phosphate, glycerophosphocholine/total phosphate, and phosphocreatine/total phosphate ratios correlated with differentiation grade, and the differences in glycerophosphorylglycerol/total phosphate ratio between metastatic and nonmetastatic sublines was highly significant. No correlation for hormonal sensitivity with any of the metabolites measured could be found, neither by 31P nor by 1H MRS. © 1994 Wiley-Liss, Inc.

In vitro 1 H and 31 P magnetic resonance spectra were acquired from perchloric acid extracts of human prostate tissue obtained by transurethral resection. This included tissue of patients with benign prostatic hyperplasia and prostatic adenocarcinoma; one tissue sample was obtained from a patient without any sign of BPH or malignancy. Major resonances in the magnetic resonance spectra were assigned to prostate compounds and were quantified. The citrate/lactate, citrate/total choline, phosphocholine/total creatinine, choline/total creatine, alanine/total creatine, phosphoethanolamine/total phosphate, phosphocholine/total phosphate and glycerophosphoethanolamine/total phosphate ratios were statistically different for the prostate cancer samples as compared with the BPH specimens. These observations may contribute to the understanding of in vivo magnetic resonance spectra of the prostate and indicate that magnetic resonance spectroscopy can aid in the diagnosis of prostate malignancy.

High energy shock waves (electromagnetically generated, Siemens Lithostar) were studied for their effects in vitro on different (tumor) cell types. Cells were exposed to the shock waves as a single cell suspension or as a cell pellet on the bottom of a test tube. In both cases, a dose dependent direct cytotoxicity, established by trypan blue dye exclusion, was observed after treatment with 1000 or 2000 shock waves. Also, the antiproliferative capacity as determined by clonogenic potential (double layer soft agar) and growth rate (plastic) were affected in this way. However, comparing the results after treatment in suspension or pellet, a discrepancy was evident. The cell lines showed a different susceptibility in pellet vs. suspension. Also the differential sensitivity of the cell types varied in these two treatment models. Furthermore the outcome depended on the cell concentration; direct cytotoxicity in a cell suspension was more pronounced at higher cell concentrations, while in a pellet this was increased by decreasing the number of cells. Finally, no shock wave induced cytotoxicity could be seen after fixation of cells in gelatine or by placing the pellet on a bottom layer of gelatine. Pressure measurements revealed no adequate explanation for this phenomenon. These results indicate that in vitro effects depend on the way cells are exposed to the shock waves and can be greatly influenced by changing the conditions of the microenvironment. Therefore, precise descriptions of the experimental set-up and careful interpretations of their outcome are obligatory.

We have studied the effect of high energy shock waves (HESW) alone or in combination with cytotoxic drugs on the growth of urological tumors. The effects of HESW on kidney or prostatic tumors depend largely on the tumor line used. In the rapidly growing prostate tumor no antitumor effect was evident in vivo, but in vitro examination of the in vivo shocked cells showed that the clonogenic potential of HESW treated cells was inhibited. In the more slowly growing tumors, like human kidney xenografts, a temporary growth delay is observed in vivo. The effect on tumor growth depends not only on the number of HESW administered but also on the initial tumor volume. The smaller the tumor burden, the better the antitumor effect. Single shock wave administration may cause a growth delay, and repeated administration leads to a prolonged delay in growth. This effect is temporary and several days after stopping the HESW administration the tumor regains its original growth potential (same doubling time). Finally we could show that tumor growth was suppressed in different tumor models for a longer period by a combination of HESW and a single dose of adriamycin. The effect of combined treatment resulted in a persistent longer doubling time.

Purpose: To improve the specificity in prostate cancer diagnosis and to prevent unnecessary prostate biopsies, especially in the serum prostate-specific antigen (PSA) ''gray zone'' between 3 and 15 ng/mL, the implementation of prostate cancer ^ specific markers is urgently needed. The recently discovered prostate cancer antigen 3 (PCA3) is such a promising prostate cancer marker. In a previous single institution study, the PCA3 urine test clearly proved to be of diagnostic value.Therefore, the diagnostic performance of the PCA3 urine test was validated in a multicenter study. Experimental Design:The first voided urine after digital rectal examination was collected from a total of 583 men with serum PSA levels between 3 and 15 ng/mL who were to undergo prostate biopsies. We determined the PCA3 score in these samples and correlated the results with the results of the prostate biopsies. Results: A total of 534 men (92%) had an informative sample. The area under the receiver- operating characteristic curve, a measure of the diagnostic accuracy of a test, was 0.66 for the PCA3 urine test and 0.57 for serum PSA. The sensitivity for the PCA3 urine test was 65%, the specificity was 66% (versus 47% for serum PSA), and the negative predictive value was 80%. Conclusions: In this multicenter study, we validated the diagnostic performance of the PCA3 urine test in the largest group studied thus far using a PCA3 gene-based test. This study shows that the PCA3 urine test, when used as a reflex test, can improve the specificity in prostate cancer diagnosis and could prevent many unnecessary prostate biopsies.

High energy shock wave lithotripsy has proven to be an effective tool in the management of renal calculi. The effects of electrohydraulically generated high energy shock waves (HESW) on tumor cells were described only recently. Here we present data on the experimental design for treatment of tumor cells, using electromagnetically generated shock waves. The determination of the focal area, in which pressures are at least 50% of the maximum pressure, appeared to be essential. In vitro HESW treatment resulted in a dose dependant anti-proliferative effect on Dunning R-3327 PAT-2 rat prostate cancer subline, determined by temporal growth curve analysis after plating of treated cells in soft agar. Furthermore, it was shown that HESW treatment had a potentiating effect on Vinblastin treatment. The combination of HESW with Vinblastin appeared to have an additive in vitro anti-proliferative effect on PAT-2 prostatic cancer cells.