M. Pilar Laguna Pes

Antibiotic Prophylaxis in Urologic Procedures: A Systematic Review

OBJECTIVE Antibiotic prophylaxis is used to minimize infectious complications resulting from interventions. Side-effects and development of microbial resistance patterns are risks of the use of antibiotics. Therefore, the use should be well considered and based on high levels of evidence. In this review, all available evidence on the use of antibiotic prophylaxis in urology is gathered, assessed, and presented in order to make choices in the use of antibiotic prophylaxis on the best evidence currently available. METHODS A systematic literature review was conducted, searching Medline, Embase (1980-2006), the Cochrane Library, and reference lists for relevant studies. All selected articles were reviewed independently by two, and, in case of discordance, three, reviewers. RESULTS Only the transurethral resection of prostate (TURP) and prostate biopsy are well studied and have a high and moderate to high level of evidence in favour of using antibiotic prophylaxis. Other urologic interventions are not well studied. The moderate to low evidence suggests no need for antibiotic prophylaxis in cystoscopy, urodynamic investigation, transurethral resection of bladder tumor, and extracorporeal shock-wave lithotripsy, whereas for therapeutic ureterorenoscopy and percutaneous nephrolithotomy, the low evidence favours the use of antibiotic prophylaxis. Urologic open and laparoscopic interventions were classified according to surgical wound classification, since no studies were identified. Antibiotic prophylaxis is not advised in clean surgery, but is advised in clean-contaminated and prosthetic surgery. CONCLUSIONS Except for the TURP and prostate biopsy, there is a lack of well-performed studies investigating the need for antibiotic prophylaxis in urologic interventions.

Novel contrast-enhanced ultrasound imaging in prostate cancer

PurposeThe purposes of this paper were to present the current status of contrast-enhanced transrectal ultrasound imaging and to discuss the latest achievements and techniques now under preclinical testing.ObjectiveAlthough grayscale transrectal ultrasound is the standard method for prostate imaging, it lacks accuracy in the detection and localization of prostate cancer. With the introduction of contrast-enhanced ultrasound (CEUS), perfusion imaging of the microvascularization became available. By this, cancer-induced neovascularisation can be visualized with the potential to improve ultrasound imaging for prostate cancer detection and localization significantly. For example, several studies have shown that CEUS-guided biopsies have the same or higher PCa detection rate compared with systematic biopsies with less biopsies needed.Materials and methodsThis paper describes the current status of CEUS and discusses novel quantification techniques that can improve the accuracy even further. Furthermore, quantification might decrease the user-dependency, opening the door to use in the routine clinical environment. A new generation of targeted microbubbles is now under pre-clinical testing and showed avidly binding to VEGFR-2, a receptor up-regulated in prostate cancer due to angiogenesis. The first publications regarding a targeted microbubble ready for human use will be discussed.ConclusionUltrasound-assisted drug delivery gives rise to a whole new set of therapeutic options, also for prostate cancer. A major breakthrough in the future can be expected from the clinical use of targeted microbubbles for drug delivery for prostate cancer diagnosis as well as treatment.

Irreversible electroporation: state of the art

The field of focal ablative therapy for the treatment of cancer is characterized by abundance of thermal ablative techniques that provide a minimally invasive treatment option in selected tumors. However, the unselective destruction inflicted by thermal ablation modalities can result in damage to vital structures in the vicinity of the tumor. Furthermore, the efficacy of thermal ablation intensity can be impaired due to thermal sink caused by large blood vessels in the proximity of the tumor. Irreversible electroporation (IRE) is a novel ablation modality based on the principle of electroporation or electropermeabilization, in which electric pulses are used to create nanoscale defects in the cell membrane. In theory, IRE has the potential of overcoming the aforementioned limitations of thermal ablation techniques. This review provides a description of the principle of IRE, combined with an overview of in vivo research performed to date in the liver, pancreas, kidney, and prostate.

Irreversible electroporation of the porcine kidney: Temperature development and distribution.

OBJECTIVE Although tissue ablation by irreversible electroporation (IRE) has been characterized as nonthermal, the application of frequent repetitive high-intensity electric pulses has the potential of substantially heating the targeted tissue and causing thermal damage. This study evaluates the risk of possible thermal damage by measuring temperature development and distribution during IRE of porcine kidney tissue. METHODS The animal procedures were conducted following an approved Institutional Animal Ethics Committee protocol. IRE ablation was performed in 8 porcine kidneys. Of them, 4 kidneys were treated with a 3-needle configuration and the remaining 4 with a 4-needle configuration. All IRE ablations consisted of 70 pulses with a length 90 µs. The pulse frequency was set at 90 pulses/min, and the pulse intensity at 1,500 V/cm with a spacing of 15 mm between the needles. The temperature was measured internally using 4 fiber-optic temperature probes and at the surface using a thermal camera. RESULTS For the 3-needle configuration, a peak temperature of 57°C (mean = 49 ± 10°C, n = 3) was measured in the core of the ablation zone and 40°C (mean = 36 ± 3°C, n = 3) at 1cm outside of the ablation zone, from a baseline temperature of 33 ± 1°C. For the 4-needle configuration, a peak temperature of 79°C (mean = 62 ± 16°C, n = 3) was measured in the core of the ablation zone and 42°C (mean = 39 ± 3°C, n = 3) at 1cm outside of the ablation zone, from a baseline of 35 ± 1°C. The thermal camera recorded the peak surface temperatures in the center of the ablation zone, reaching 31°C and 35°C for the 3- and 4-needle configuration IRE (baseline 22°C). CONCLUSIONS The application of repetitive high-intensity electric pulses during IRE ablation in porcine kidney causes a lethal rise in temperature within the ablation zone. Temperature monitoring should be considered when performing IRE ablation near vital structures.

Clinical update on testicular microlithiasis

Purpose of review Testicular microlithiasis becomes a greater interdisciplinary issue among urologists, andrologists, gynecologists dedicated to reproductive medicine, pediatricians, radiologists and pathologists. Proposed management ranges from benign neglect, instructing self-examination over follow-up once, regular biannual follow-up including ultrasonography to bilateral testicular biopsy to rule out possible concomitant unclassified intratubular germ cell neoplasia (ITGCN) or future development of testicular cancer. The aim of this review is to present an overview of the current dilemma and summarize management trends based on the most recent data. Recent findings Testicular microlithiasis is not a premalignant condition but may accompany ITGCN or testicular cancer. The importance of ruling out ITGCN with testicular biopsy in high-risk men, such as in those with bilateral testicular microlithiasis, infertility, cryptorchidism, atrophic testes or contralateral testicular cancer, has been recently advocated. Summary Despite greater awareness of testicular microlithiasis, a clear definition is currently missing and the etiology is still obscure. This causes confusion in management and follow-up. Self-examination alone or in combination with testicular ultrasonography has been advised. Recently, a single set of biopsies in selected, high-risk groups has been proposed to rule out ITGCN without a need for further investigations apart from self-examination. However, the cost-effectiveness of such a strategy needs to be evaluated.

Immediate Effect of Kidney Cryoablation on Renal Arterial Structure in a Porcine Model Studied by Imaging Cryomicrotome

PURPOSE Injury to blood microvessels has a crucial role in effective cryoablation for renal masses. We visualized vascular injury induced by a clinically applied cryoablation instrument and established a microvascular diameter threshold for vascular damage. MATERIALS AND METHODS In 5 anesthetized pigs 1 kidney each was exposed and 3, 17 gauge cryoneedles were inserted in 1 pole. Tissue was exposed to freezing for 2 x 10 minutes with a 10-minute thaw between freezes. After nephrectomy the arteries were injected with fluorescence dyed casting material and the kidney was frozen to -20C and cut in 40 to 60 micron slices in the imaging cryomicrotome, where fluorescent images of the cutting plane of the bulk were obtained. This resulted in a 3-dimensional image of the arterial tree that was segmented, resulting in unbranched vessel segments. Histograms were constructed with the total segment length per diameter bin plotted as function of diameter. RESULTS The ablated zone was sharply demarcated on fluorescent and normal light images. Mean +/- SD diameter at the peak of the histogram from control areas was 152.4 +/- 5.3 micron. Compared to control areas the peak diameter of ablated areas was shifted to a larger diameter by an average of 25.4 +/- 2.6 micron. CONCLUSIONS Immediate renal cryoablation injury destroys arteries smaller than 180 micron. Branching structures of larger arteries remain anatomically intact and connected to vascular structures in surrounding tissue.

Trends in epidemiology and treatment of upper urinary tract tumours in the Netherlands 1995-2005: an analysis of PALGA, the Dutch national histopathology registry

Study Type – Therapy (prospective cohort)
Level of Evidence 2b

Testicular Tumour Size and Rete Testis Invasion as Prognostic Factors for the Risk of Relapse of Clinical Stage I Seminoma Testis Patients Under Surveillance: a Systematic Review by the Testicular Cancer Guidelines Panel

CONTEXT Patients with clinical stage I (CS I) seminoma testis with large primary tumours and/or rete testis invasion (RTI) might have an increased risk of relapse. In recent years, these risk factors have frequently been employed to decide on adjuvant treatment. OBJECTIVE To systematically review the literature on tumour size and RTI as risk factors for relapse in CS I seminoma testis patients under surveillance. EVIDENCE ACQUISITION Relevant databases including Medline, Embase, and the Cochrane Library were searched up to November 2016. Randomised controlled trials (RCTs) or quasi-RCTs, prospective observational studies with controls, retrospective matched-pair studies, and comparative studies from well-defined registries/databases were included. The primary outcome was the rate of relapse and relapse-free survival (RFS). The risk of bias was assessed by the Quality in Prognosis Studies tool. EVIDENCE SYNTHESIS After assessing 3068 abstracts and 80 full-text articles, 20 studies met the inclusion criteria. Although evidence to justify a cut-off of 4cm for size was lacking, it was the most frequently studied. The reported hazard ratio (HR) for the RFS for tumours >4cm was 1.59-2.8. Accordingly, the reported 5-yr RFS ranged from 86.6% to 95.5% and from 73.0% to 82.6% for patients having tumours ≤4 and >4cm, respectively. For tumours with RTI present, the reported HR was 1.4-1.7. The 5-yr RFS ranged from 86.0% to 92.0% and 74.9% to 79.5% for patients without versus those with RTI present, respectively. A meta-analysis was considered inappropriate due to data heterogeneity. CONCLUSIONS Primary tumour size and RTI are associated with the risk of relapse in CS I seminoma testis patients during surveillance. However, in the presence of either risk factor, the vast majority of patients are cured by orchiectomy alone and will not relapse. Furthermore, the evidence on the prognostic value of size and RTI has significant limitations, so prudency is warranted on their routine use in clinical practice. PATIENT SUMMARY Primary testicular tumour size and rete testis invasion are considered to be important prognostic factors for the risk of relapse in patients with clinical stage I seminoma testis. We systematically reviewed all the literature on the prognostic value of these two postulated risk factors. The outcome is that the prognostic power of these factors in the published literature is too low to advocate their routine use in clinical practice and to drive the choice on adjuvant treatment in clinical stage I seminoma testis patients.

In vivo, percutaneous, needle based, optical coherence tomography of renal masses

Optical coherence tomography (OCT) is the optical equivalent of ultrasound imaging, based on the backscattering of near infrared light. OCT provides real time images with a 15 µm axial resolution at an effective tissue penetration of 2-3 mm. Within the OCT images the loss of signal intensity per millimeter of tissue penetration, the attenuation coefficient, is calculated. The attenuation coefficient is a tissue specific property, providing a quantitative parameter for tissue differentiation. Until now, renal mass treatment decisions have been made primarily on the basis of MRI and CT imaging characteristics, age and comorbidity. However these parameters and diagnostic methods lack the finesse to truly detect the malignant potential of a renal mass. A successful core biopsy or fine needle aspiration provides objective tumor differentiation with both sensitivity and specificity in the range of 95-100%. However, a non-diagnostic rate of 10-20% overall, and even up to 30% in SRMs, is to be expected, delaying the diagnostic process due to the frequent necessity for additional biopsy procedures. We aim to develop OCT into an optical biopsy, providing real-time imaging combined with on-the-spot tumor differentiation. This publication provides a detailed step-by-step approach for percutaneous, needle based, OCT of renal masses.

Confocal Laser Endomicroscopy for the Diagnosis of Urothelial Carcinoma in the Bladder and the Upper Urinary Tract: Protocols for Two Prospective Explorative Studies

Background Visual confirmation of a suspicious lesion in the urinary tract is a major corner stone in diagnosing urothelial carcinoma. However, during cystoscopy (for bladder tumors) and ureterorenoscopy (for tumors of the upper urinary tract) no real-time histopathologic information can be obtained. Confocal laser endomicroscopy (CLE) is an optical imaging technique that allows for in vivo high-resolution imaging and may allow real-time tumor grading of urothelial lesions. Objective The primary objective of both studies is to develop descriptive criteria for in vivo CLE images of urothelial carcinoma (low-grade, high-grade, carcinoma in situ) and normal urothelium by comparing CLE images with corresponding histopathology. Methods In these two prospective clinical trials, CLE imaging will be performed of suspicious lesions and normal tissue in the urinary tract during surgery, prior to resection or biopsy. In the bladder study, CLE will be performed in 60 patients using the Cystoflex UHD-R probe. In the upper urinary tract study, CLE will be performed in 25 patients during ureterorenoscopy, who will undergo radical treatment (nephroureterectomy or segmental ureter resection) thereafter. All CLE images will be analyzed frame by frame by three independent, blinded observers. Histopathology and CLE-based diagnosis of the lesions will be evaluated. Both studies comply with the IDEAL stage 2b recommendations. Results Presently, recruitment of patients is ongoing in both studies. Results and outcomes are expected in 2018. Conclusions For development of CLE-based diagnosis of urothelial carcinoma in the bladder and the upper urinary tract, a structured conduct of research is required. This study will provide more insight in tissue-specific CLE criteria for real-time tumor grading of urothelial carcinoma. Trial Registration Confocal Laser Endomicroscopy: ClinicalTrials.gov NCT03013894; https://clinicaltrials.gov /ct2/show/NCT03013894?term=NCT03013894&rank=1 (Archived by WebCite at http://www.webcitation.org/6wiPZ378I); and Dutch Central Committee on Research Involving Human Subjects NL55537.018.15; https://www.toetsingonline.nl /to/ccmo_search.nsf/fABRpop?readform&unids=6B72AE6EB0FC3C2FC125821F001B45C6 (Archived by WebCite at http://www.webcitation.org/6wwJQvqWh). Confocal Laser Endomicroscopy in the upper urinary tract: ClinicalTrials.gov NCT03013920; https://clinicaltrials.gov/ct2/show/NCT03013920? term=NCT03013920&rank=1 (Archived by WebCite at http://www.webcitation.org/6wiPkjyt0); and Dutch Central Committee on Research Involving Human Subjects NL52989.018.16; https://www.toetsingonline.nl/to/ccmo_search.nsf/fABRpop?readform&unids=D27C9C3E5755CFECC12581690016779F (Archived by WebCite at http://www.webcitation.org/6wvy8R44C).