Rob F.M. Bevers

Real-Time Cancer Cell Tracking by Bioluminescence in a Preclinical Model of Human Bladder Cancer Growth and Metastasis

BACKGROUND Bladder cancer is the fifth most common malignancy in the Western world and the second most frequently diagnosed genitourinary tumor. In the majority of cases, death from bladder cancer results from metastatic disease. Understanding the multistep process of carcinogenesis and metastasis in urothelial cancers is pivotal to the development of new therapeutic strategies. Molecular imaging of cancer growth and metastasis in preclinical models provides the essential link between cell-based experiments and clinical translation. OBJECTIVE Develop preclinical models for sensitive bladder cancer cell tracking during tumor progression and metastasis. DESIGN, SETTING, AND PARTICIPANTS A human transitional cell carcinoma UM-UC-3 cell line was generated that stably expresses luciferase 2 (UM-UC-3luc2), a mammalian codon-optimized firefly luciferase with superior expression. Preclinical models were developed with human UM-UC-3luc2 cells xenografted into the bladder (orthotopic model with metastases) or inoculated into the left cardiac ventricle (bone metastasis model) of immunocompromised mice. MEASUREMENTS Noninvasive, sensitive bioluminescent imaging of human firefly luciferase 2-positive bladder cancer in mice using the IVIS100 imaging system. RESULTS AND LIMITATIONS In the orthotopic model (intravesical inoculation), tumor growth could be followed directly after inoculation of UM-UC-3luc2 cells. Importantly, micrometastatic lesions originating from orthotopically implanted cancer cells could be detected in the locoregional lymph nodes and in distant organs. In addition, the superior bioluminescent indicator firefly luciferase 2 allows the detection and monitoring of micrometastatic lesions in real time after intracardiac inoculation of human bladder cancer cells in mice. The main disadvantage is the lack of T-cell immunity in the preclinical models. CONCLUSIONS The new bioluminescence-based preclinical bladder cancer models enable superior, noninvasive, and real-time tracking of cancer cells, tumor progression, and micrometastasis. Because of the significant improvement in detection of small cell numbers, the presented models are ideally suited for functional studies dealing with minimal residual disease as well as real-time imaging of drug response.

Transurethral and suprapubic mesh resection after Prolift® bladder perforation: a case report

Bladder perforation is a complication which can occur after a Prolift® procedure and may enhance vesicovaginal fistula formation. Different methods of management of bladder perforation caused by mesh procedures are described in the literature, and most authors advise complete excision of the mesh. In the case described in this article, we propose a combined transurethral and suprapubical approach as the optimal method for maximal tape removal, being both minimally invasive and less damaging to the vesical wall. A suprapubical catheter can be removed shortly after surgery to enable optimal tissue healing of the vesical mucosa.

Effect of preoperative pelvic floor muscle therapy with biofeedback versus standard care on stress urinary incontinence and quality of life in men undergoing laparoscopic radical prostatectomy: A randomised control trial

Laparoscopic radical prostatectomy (LARP) may cause stress urinary incontinence (SUI). This study reports the effects of preoperative pelvic floor muscle therapy (PFMT) on SUI and quality of life (QoL) in men undergoing LARP.

Effect of variations in depth of neuromuscular blockade on rating of surgical conditions by surgeon and anesthesiologist in patients undergoing laparoscopic renal or prostatic surgery (BLISS trial): study protocol for a randomized controlled trial

BackgroundSurgical conditions in laparoscopic surgery are largely determined by the depth of neuromuscular relaxation. Especially in procedures that are confined to a narrow working field, such as retroperitoneal laparoscopic surgery, deep neuromuscular relaxation may be beneficial. Until recently, though, deep neuromuscular block (NMB) came at the expense of a variety of issues that conflicted with its use. However, with the introduction of sugammadex, rapid reversal of a deep NMB is feasible. In the current protocol, the association between the depth of NMB and rating of surgical conditions by the surgeon and anesthesiologist is studied.Methods/designThis is a single-center, prospective, randomized, blinded, parallel group and controlled trial. Eligible patients are randomly assigned to one of two groups: (1) deep NMB (post-tetanic count, one or two twitches; n = 12) and (2) moderate NMB (train-of-four, 1 to 2 twitches, n = 12) by administration of high-dose rocuronium in Group 1 and a combination of atracurium and mivacurium in Group 2. The NMB in Group 1 is reversed by 4 mg/kg sugammadex; the NMB in Group 2 by 1 mg neostigmine and 0.5 mg atropine. Patients are eligible if they are over 18 years, willing to sign the informed consent form, and are scheduled to undergo an elective laparoscopic renal procedure or laparoscopic prostatectomy. A single surgeon performs the surgeries and rates the surgical conditions on a five-point surgical rating scale (SRS) ranging from 1 (poor surgical conditions) to 5 (excellent surgical conditions). The intra-abdominal part of the surgeries is captured on video and a group of five anesthesiologists and ten surgical experts will rate the videos using the same SRS. The primary analysis will be an intention-to-treat analysis. Evaluation will include the association between the level of NMB and SRS, as obtained by the surgeon performing the procedure and the agreement between the scoring of the images by anesthesiologists and surgeons.DiscussionWe aim to show that under the right conditions the perceived opposing goals of surgeons and anesthesiologists (optimal surgical conditions vs. optimal postoperative conditions) may be met without compromise to either.Trial registrationClinicalTrials.gov identifier NCT01631149.

Testis calcification of the tunica albuginea.

Sir, A 79 year-old man presented with a calcification of the left hemiscrotum accidentally found on plain X-ray during evaluation of joint pain (Fig. 1). There was no previous history of epididymitis, testicular torsion or trauma. Plain X-ray performed 4 years earlier showed no calcification. Physical examination revealed an abnormal, hard left testis. The right testis and epididymis were normal. Laboratory analysis showed normal AFP and β-HCG. Scrotal sonogram confirmed calcification of the tunica albuginea testis. As malignancy was not excluded by ultrasound, a left radical orchiectomie was performed. The orchiectomy specimen contained a calcified tunica albuginea (Fig. 2) and a normal funiculus in the surrounding fat tissue. The histological report revealed the tunica albuginea to consist of completely calcified dense fibrous tissue. The testis showed extensive

Laparoscopic Practice Patterns in the Netherlands in 2005

PURPOSE To assess the status of urologic laparoscopy in the Netherlands in 2005. MATERIALS AND METHODS A personal e-mail survey was sent to all practicing Dutch urologists to assess the urologic laparoscopic practice patterns in the Netherlands in 2005. RESULTS Data were gathered from 86.8% of all urologists receiving the survey. In 2005, 25.5% of Dutch urologists performed laparoscopic procedures. The median number of laparoscopic procedures per urologist was low: 23 per year. Of all non-laparoscopists, 28.5% indicated an intent to begin performing laparoscopic procedures within 1 year. CONCLUSION All currently performed laparoscopic urologic procedures were performed in the Netherlands in 2005, but the number of such procedures performed per year is low.

Impact of high- versus low-dose neuromuscular blocking agent administration on unplanned 30-day readmission rates in retroperitoneal laparoscopic surgery

Recent data shows that a neuromuscular block (NMB) induced by administration of high doses of rocuronium improves surgical conditions in certain procedures. However, there are limited data on the effect such practices on postoperative outcomes. We performed a retrospective analysis to compare unplanned 30-day readmissions in patients that received high-dose versus low-dose rocuronium administration during general anesthesia for laparoscopic retroperitoneal surgery. This retrospective cohort study was performed in the Netherlands in an academic hospital where routine high-dose rocuronium NMB has been practiced since July 2015. Charts of patients receiving anesthesia between January 2014 and December 2016 were searched for surgical cases receiving high-dose rocuronium and matched with respect to procedure, age, sex and ASA classification to patients receiving low-dose rocuronium. The primary post-operative outcome was unplanned 30-day readmission rate. There were 130 patients in each cohort. Patients in the high- and low-dose rocuronium cohorts received 217 ± 49 versus 37 ± 5 mg rocuronium, respectively. In the high-dose rocuronium group neuromuscular activity was consistently monitored; matched patients were unreliably monitored. All patients receiving high-dose rocuronium were reversed with sugammadex, while just 33% of matched patients were reversed with sugammadex and 20% with neostigmine; the remaining patients were not reversed. Unplanned 30-day readmission rate was significantly lower in the high-dose compared to the low-dose rocuronium cohort (3.8% vs. 12.7%; p = 0.03; odds ratio = 0.33, 95% C.I. 0.12–0.95). This small retrospective study demonstrates a lower incidence of unplanned readmissions within 30-days following laparoscopic retroperitoneal surgery with high-dose relaxant anesthesia and sugammadex reversal in comparison to low-dose relaxant anesthesia. Further prospective studies are needed in larger samples to corroborate our findings and additionally assess the pharmacoeconomics of high-dose relaxant anesthesia taking into account the benefits (reduced readmissions) and harm (cost of relaxants and reversal agents) of such practice.

Urologische laparoscopie in getal: enquête onder Nederlandse urologen

SamenvattingIntroductie:Urologische laparoscopie wordt reeds 2 decennia beoefend, maar inzicht in het aantal uitgevoerde laparoscopische ingrepen ontbreekt. In deze studie is het aantal laparoscopische ingrepen dat in Nederland in 2009 werd uitgevoerd geïnventariseerd. De uitkomsten zijn vergeleken met de uitkomsten van een inventarisatie over 2005.Methoden:Er is een enquête verstuurd aan alle Nederlandse urologen.Resultaten:Gegevens van 287 (85%) urologen zijn verzameld tegenover gegevens van 263 urologen (87%) in 2005. Laparoscopische urologie werd in 61% van alle samenwerkingsverbanden beoefend (45% in 2005). Van alle respondenten verrichtten er 88 (31%) laparoscopische ingrepen ten opzichte van 67 (26%) in 2005. Het totale aantal laparoscopische ingrepen steeg van 2308 in 2005 naar 4129 in 2009. Van deze 2308 ingrepen waren er 682 (16,5%) robotgeassisteerd. Het aantal ingrepen per uroloog steeg ook, met een mediaan van 23 in 2005 naar 32 in 2009. Van alle respondenten die geen laparoscopie beoefenden, was 11% van plan hier binnen 1 jaar mee te starten.Conclusie:De resultaten van deze studie illustreren de toegenomen populariteit van laparoscopie binnen de urologie in Nederland. De cijfers van deze studie kunnen bijdragen aan de actuele discussie over het minimale aantal te verrichten ingrepen.SummaryDutch urologic laparoscopy: a survey on practice patternsIntroduction:Urologic laparoscopy has been practiced since two decades. However, the extent of laparoscopy is unknown. In this study the status of urologic laparoscopy in the Netherlands in 2009 was assessed and compared with the results of a survey performed in 2005.Methods:A questionnaire was sent to all practicing Dutch urologists.Results:Data of 287 (84.7%) urologists was gathered versus 263 (86.8%) in 2005. Laparoscopic urology was practiced in 61% of all urologic practices (45% in 2005). Of all responding urologists, 88 (30.7%) performed laparoscopic procedures, compared to 67 (25.5%) in 2005. The total number of laparoscopic procedures increased from 2308 in 2005 to 4129 in 2009. New is the robot assisted procedure, 682 (16,5%) of these procedures were performed in 2009. The median number of laparoscopic procedures per urologist increased from 23 in 2005 to 32 in 2009. Of all responding urologists that did not practice laparoscopy, 11% indicated they planned to start within one year.Conclusion:The results of this study demonstrate the rapidly increasing popularity of laparoscopy in Dutch urology. The results of this study can assist the current discussion about threshold volumes.

Reoperation Rate in Patients with a Continent Urinary Diversion or Neobladder Is Influenced by the Oncological or Functional Indication for Cystectomy

Purpose: Continent urinary diversion following a cystectomy has become a standard procedure in suitable patients, because of its potentially favorable aspects. Reports concerning long-term complications necessitating reoperation are mainly based on patients with cystectomy for carcinoma. We reviewed the reoperation rate in patients with a continent diversion for both oncological and interstitial cystitis. Materials and Methods: A retrospective study was performed at our department on 63 patients in whom a continent diversion was created in the period from 1984 to 2002. Mean follow-up period was 73.9 months. Statistical analysis for the postoperative complication rate was performed using a multivariate linear stepwise regression, and Cox proportional hazard model. Results: Mean patient-age for the whole group was 53.8 years. Types of diversion used were Indiana (n = 31), Hautmann (n = 21) and Kock (n = 11). The group with an oncological indication for cystectomy consisted of 40 patients (31 male, 9 female) with a mean age of 58.5 years. Reasons for cystectomy were transitional cell carcinoma of the bladder (n = 39) and clear cell vaginal carcinoma (n = 1). The cystitis group was comprised of 23 patients (2 male, 21 female) with a mean age of 45.7 years. Cystectomy was performed for interstitial cystitis (n = 20) and chronic cystitis (n = 3). Multivariate linear stepwise regression of the summed side-effect score yielded a significant association, with the oncological group having less postoperative complications. The Cox proportional hazard model yielded a highly significant difference in revision of the urinary diversion. Reoperation rate in functional patients was 78.3 vs. 22.5% in oncological patients (p < 0.001). Conclusions: Postoperative complication and reoperation rates of continent diversion (or orthotopic neobladder) were significantly higher in patients with non-oncological indications for cystectomy. Therefore, results of continent diversion based on studies with oncological patients should not be used in counselling patients who may need a urinary diversion because of functional reasons such as interstitial cystitis.