J.J.M.C.H. de la Rosette

Focal Therapy in Prostate Cancer—Report from a Consensus Panel

PURPOSE To establish a consensus in relation to case selection, conduct of therapy, and outcomes that are associated with focal therapy for men with localized prostate cancer. MATERIAL AND METHODS Urologic surgeons, radiation oncologists, radiologists, and histopathologists from North America and Europe participated in a consensus workshop on focal therapy for prostate cancer. The consensus process was face to face within a structured meeting, in which pertinent clinical issues were raised, discussed, and agreement sought. Where no agreement was possible, this was acknowledged, and the nature of the disagreement noted. RESULTS Candidates for focal treatment should have unilateral low- to intermediate-risk disease with clinical stage <or=cT(2a). Prostate size and both tumor volume and tumor topography are important case selection criteria that depend on the ablative technology used. Currently, the best method to ascertain the key characteristics for men who are considering focal therapy is exposure to transperineal template mapping biopsies. MRI of the prostate using novel techniques such as dynamic contrast enhancement and diffusion weighed imaging are increasingly being used to diagnose and stage primary prostate cancer with excellent results. For general use, however, these new techniques require validation in prospective clinical trials. Until such are performed, MRI will, in most centers, continue to be an investigative tool in assessing eligibility of patients for focal therapy. CONCLUSIONS Consensus was derived for most of the key aspects of case selection, conduct of treatment, and outcome measures for men who are undergoing focal therapy for localized prostate cancer. The level of agreement achieved will pave the way for future collaborative trials.

Embryonic stem cell-like cells derived from adult human testis

BACKGROUND Given the significant drawbacks of using human embryonic stem (hES) cells for regenerative medicine, the search for alternative sources of multipotent cells is ongoing. Studies in mice have shown that multipotent ES-like cells can be derived from neonatal and adult testis. Here we report the derivation of ES-like cells from adult human testis. METHODS Testis material was donated for research by four men undergoing bilateral castration as part of prostate cancer treatment. Testicular cells were cultured using StemPro medium. Colonies that appeared sharp edged and compact were collected and subcultured under hES-specific conditions. Molecular characterization of these colonies was performed using RT-PCR and immunohistochemistry. (Epi)genetic stability was tested using bisulphite sequencing and karyotype analysis. Directed differentiation protocols in vitro were performed to investigate the potency of these cells and the cells were injected into immunocompromised mice to investigate their tumorigenicity. RESULTS In testicular cell cultures from all four men, sharp-edged and compact colonies appeared between 3 and 8 weeks. Subcultured cells from these colonies showed alkaline phosphatase activity and expressed hES cell-specific genes (Pou5f1, Sox2, Cripto1, Dnmt3b), proteins and carbohydrate antigens (POU5F1, NANOG, SOX2 and TRA-1-60, TRA-1-81, SSEA4). These ES-like cells were able to differentiate in vitro into derivatives of all three germ layers including neural, epithelial, osteogenic, myogenic, adipocyte and pancreatic lineages. The pancreatic beta cells were able to produce insulin in response to glucose and osteogenic-differentiated cells showed deposition of phosphate and calcium, demonstrating their functional capacity. Although we observed small areas with differentiated cell types of human origin, we never observed extensive teratomas upon injection of testis-derived ES-like cells into immunocompromised mice. CONCLUSIONS Multipotent cells can be established from adult human testis. Their easy accessibility and ethical acceptability as well as their non-tumorigenic and autogenic nature make these cells an attractive alternative to human ES cells for future stem cell therapies.

Prognostic Factors and Percutaneous Nephrolithotomy Morbidity: A Multivariate Analysis of a Contemporary Series Using the Clavien Classification

PURPOSE We stratified factors affecting treatment morbidity, compared the outcomes of percutaneous nephrolithotomy procedures from a single department and provided evidence of treatment benefits when percutaneous nephrolithotomy is performed in an expert setting. MATERIALS AND METHODS Since the department became a dedicated endourological center in 2002 we grouped all percutaneous nephrolithotomy procedures into those performed before 2002 (group 1) and after 2002 (group 2). The modified Clavien classification was used to score morbidity. Independent variables with an influence on complications were studied including stone size, operating time, operative complications, dilation device, urine culture, group allocation and lithotripsy device. Contingency and logistic regression were used for univariate and multivariate analysis. RESULTS Of the 244 percutaneous nephrolithotomy procedures 68 comprised group 1 and 176 formed group 2. Statistical preoperative differences were patient age, the use of anticoagulants and positive urinary cultures. Group 1 had a complication rate of 56.8% and group 2 had a complication rate of 37.2%. There were significant differences between the groups (p = 0.007). Almost all complications were grade 1 to 2. On univariate analysis the influence variables were urine culture (OR 1.69), group allocation (OR 2.20), stone size (OR 2.28), dilation device (OR 4.8), lithotripsy device (OR 1.22), perioperative complications (OR 2.83) and surgical time (OR 1.87). On multivariate analysis the independent factors in the complicated outcome were stone size (OR 1.25), type of lithotripsy device (OR 1.35) and incidence of perioperative complications (OR 3.71). CONCLUSIONS The dedicated setting for percutaneous nephrolithotomy at our center resulted in decreased operative time, more uneventful procedures and decreased hospitalization time. The modified Clavien morbidity score is a reliable tool for more objective outcome comparisons after renal stone treatment.

MR imaging of the male pelvis

Abstract. Prostate and urinary bladder cancer are the most frequently encountered malignancies of the urinary tract. Appropriate use of the different imaging techniques is crucial for accurate assessment of prognosis and for the development of appropriate treatment planning. Especially determination of local tumor extension and detection of nodal or bone metastases is extremely important. In this regard MR imaging is the most promising imaging technique. Therefore, in this review its role in staging these malignancies is evaluated and compared with clinical staging, and other imaging techniques. Finally, future developments, such as new sequences, new contrast agents, the role of surface coils and MR-guided biopsy, are considered. Also, the preferred radiological approach is discussed.

The safety and efficacy of irreversible electroporation for the ablation of prostate cancer: a multicentre prospective human in vivo pilot study protocol

Introduction Current surgical and ablative treatment options for prostate cancer have a relatively high incidence of side effects, which may diminish the quality of life. The side effects are a consequence of procedure-related damage of the blood vessels, bowel, urethra or neurovascular bundle. Ablation with irreversible electroporation (IRE) has shown to be effective in destroying tumour cells and harbours the advantage of sparing surrounding tissue and vital structures. The aim of the study is to evaluate the safety and efficacy and to acquire data on patient experience of minimally invasive, transperineally image-guided IRE for the focal ablation of prostate cancer. Methods and analysis In this multicentre pilot study, 16 patients with prostate cancer who are scheduled for a radical prostatectomy will undergo an IRE procedure, approximately 30 days prior to the radical prostatectomy. Data as adverse events, side effects, functional outcomes, pain and quality of life will be collected and patients will be controlled at 1 and 2 weeks post-IRE, 1 day preprostatectomy and postprostatectomy. Prior to the IRE procedure and the radical prostatectomy, all patients will undergo a multiparametric MRI and contrast-enhanced ultrasound of the prostate. The efficacy of ablation will be determined by whole mount histopathological examination, which will be correlated with the imaging of the ablation zone. Ethics and dissemination The protocol is approved by the ethics committee at the coordinating centre (Academic Medical Center (AMC) Amsterdam) and by the local Institutional Review Board at the participating centres. Data will be presented at international conferences and published in peer-reviewed journals. Conclusions This pilot study will determine the safety and efficacy of IRE in the prostate. It will show the radiological and histopathological effects of IRE ablations and it will provide data to construct an accurate treatment planning tool for IRE in prostate tissue. Trial registration number Clinicaltrials.gov database: NCT01790451.

Amyloidosis of the seminal vesicles simulating tumor invasion of prostatic carcinoma on endorectal MR images

Abstract. Amyloid deposits within the seminal vesicles are a common finding at autopsy. The incidence increases with age. Amyloid deposits can mimic tumor extension into the seminal vesicles due to prostate or bladder cancer on T2-weighted MR images. We describe a case of seminal vesicle amyloidosis demonstrating the MR appearance and the characteristic pathologic findings. Recognizing seminal vesicle amyloidosis may prevent overstaging prostate cancer on MR images.

MR Lymphangiography for Detection of Minimal Nodal Disease in Patients with Prostate Cancer

RATIONALE AND OBJECTIVES As prostate cancer is the second leading cause of cancer death in men in the USA, the clinical challenge is to develop methods that allow early diagnosis, accurate staging and precise treatment. Metastases to local and distant lymph nodes play a major role in the choice of therapy and in predicting outcome of these patients (1). Clinical examination to detect lymph node metastases alone is inadequate and surgical dissection and serial histologic examinations are currently accepted “yardsticks”. In the past years, there has been debate about the pros and cons of total lymph node resection, particularly because of its morbidity, lengthiness of the surgical procedure and the resources necessary for complete pathologic evaluation of harvested nodes (2). Non-invasive imaging techniques for the detection of lymph node metastases would be of great help and a potential cost savings (imaging study vs. surgical lymphadenectomy) in the evaluation and re-staging of cancer patients. All current cross sectional imaging techniques (US, CT and MRI) have a relatively low sensitivity in detecting nodal metastases primarily because detection relies on insensitive size criteria (10 mm short axis) (3). Ultrasmall superparamagnetic iron oxide (USPIO) is a relatively new RES targeted MR contrast agent that is known for lymph node uptake (4-13). The purpose of this study was to evaluate the utility of USPIO (Combidex ™; Sinerem) induced signal intensity changes in lymph nodes for staging patients with prostate cancer. Also assessed was the utility of postcontrast images alone in characterizing lymph nodes.

Standardization of definitions in focal therapy of prostate cancer: report from a Delphi consensus project

PurposeTo reach standardized terminology in focal therapy (FT) for prostate cancer (PCa).MethodsA four-stage modified Delphi consensus project was undertaken among a panel of international experts in the field of FT for PCa. Data on terminology in FT was collected from the panel by three rounds of online questionnaires. During a face-to-face meeting on June 21, 2015, attended by 38 experts, all data from the online rounds were reviewed and recommendations for definitions were formulated.ResultsConsensus was attained on 23 of 27 topics; TargetedFT was defined as a lesion-based treatment strategy, treating all identified significant cancer foci; FT was generically defined as an anatomy-based (zonal) treatment strategy. Treatment failure due to the ablative energy inadequately destroying treated tissue is defined as ablation failure. In targeting failure the energy is not adequately applied to the tumor spatially and selection failure occurs when a patient was wrongfully selected for FT. No definition of biochemical recurrence can be recommended based on the current data. Important definitions for outcome measures are potency (minimum IIEF-5 score of 21), incontinence (new need for pads or leakage) and deterioration in urinary function (increase in IPSS >5 points). No agreement on the best quality of life tool was established, but UCLA-EPIC and EORTC-QLQ-30 were most commonly supported by the experts. A complete overview of statements is presented in the text.ConclusionFocal therapy is an emerging field of PCa therapeutics. Standardization of definitions helps to create comparable research results and facilitate clear communication in clinical practice.

Present Practice and Development of Minimally Invasive Techniques, Imaging and Training in European Urology: Results of a Survey of the European Society of Uro-Technology (ESUT)

OBJECTIVES The European Society of Urological Technology (ESUT) conducted a survey in order to assess and record the current trend between European urologists with regard to the application of new technologies in BPH, stone disease and imaging and to identify differences amongst urologists. MATERIAL AND METHODS A total of 854 certified urologists and residents coming from European countries answered the ESUT survey during the XVIth Annual EAU Meeting in Geneva in 2001. The respondents were classified according to the geographical origin (Eastern, Southern and Northern Europe), year of certification (before 1980, and every 5 years hereafter) and power of the department in beds (less than 25, 26-50, and more than 50) in order to identify any differences in the replies mainly due to economical reasons, national or hospital policy and personal attitudes. RESULTS According to the replies, in Eastern Europe more procedures related to BPH and stones are performed comparing to Northern and Southern Europe (165.8 versus 77.1 and 100.6/month/department, respectively). However, the Northern European urologists have access to every type of lithotriptor and most of the different minimally invasive treatments for BPH in a higher percentage, followed by the Southern and the Eastern European urologists. The most widespread intracorporeal lithotriptor is the pneumatic and the most common alternative minimally invasive BPH treatment is electrovaporization (80.7% and 45.6%, respectively). Holmium laser is the most frequent choice (40.1%) when the surveyed urologists were asked to choose which of the minimally invasive techniques would like to have access to. In total 79.4% (54.1% alone and 25.3% in collaboration with the radiologists) of the respondents perform the ultrasound studies while the remaining 20.6% declare that only the radiologists do the studies. Of the surveyed urologists, 92.8%, 89.6% and 94.9% are interested in hands-on courses, simulators and live surgery, respectively. CONCLUSIONS The data obtained from the 854 surveyed European urologists and residents can be used as a tool to highlight the disparity between European countries and to advance training of European urologists.

Evaluation of renal masses with contrast-enhanced ultrasound

The clinical need for characterising small renal masses (SRMs) is increasing due to their rising incidental detection. This increase is especially seen in younger and older generations and concerns mainly SRMs. Diagnostics is mainly made by contrast-enhanced CT or MRI. However, these imaging methods fail to accurately distinguishing benign from malignant SRMs. Other disadvantages of CT or MRI are high costs, the use of ionizing radiation, nephrotoxicity induced by iodine contrast agents or nephrogenic systemic fibrosis (NSF) induced by gadolinium contrast agents. Contrast-enhanced ultrasound (CEUS) is based on ultrasonography and microbubbles to real-time visualize the renal blood flow without the use of nephrotoxic agents or ionizing radiation. This comprehensive review evaluates the capabilities of CEUS in the diagnostics of benign (angiomyolipomas, cysts, oncocytomas, pseudotumors) and malignant masses (renal cell carcinomas), and focuses on possible future treatment.