Etienne Xavier Keller

Polyomavirus BK and prostate cancer: a complex interaction of potential clinical relevance.

Several studies associating BK polyomavirus (BKPyV) and prostate cancer (PCa) suggested that this virus may exert its oncogenic activity at early stages of cancer development. The BKPyV oncogene, the large T antigen (LTag), has frequently been detected in areas of proliferative inflammatory atrophy, which is considered a precursor lesion leading to prostatic intraepithelial neoplasia and overt PCa. In a recently updated systematic review, the presence of BKPyV was significantly higher in PCa tissues than in healthy control tissues, providing an indication for a link between BKPyV infection and cancer risk. In addition, recent original investigations highlighted an association between expression of the virus and the clinical course of PCa. For example, by studying immune responses elicited against BKPyV LTag, a significant association between LTag positive cancer lesions and a peculiar regulatory profiling has been observed in PCa patients with evidence of disease recurrence after surgical radical prostatectomy. Lastly, a study carried out in a larger cohort of patients undergoing radical prostatectomy revealed the IgG response against LTag as an independent predictor of disease recurrence. Although a full picture of the mechanisms potentially responsible for the involvement of BKPyV in PCa is not available yet, continuing work on this topic should help to refine the potential role of BKPyV in PCa patients, perhaps revealing unsuspected associations with the clinical course of this disease. Copyright

High VEGF-D and Low MMP-2 Serum Levels Predict Nodal-Positive Disease in Invasive Bladder Cancer

Background To investigate stromal variables including angiogenesis, lymphangiogenesis, and matrix metalloproteinase (MMP) in the serum of patients with urothelial carcinoma of the bladder (UCB) and to evaluate their association with histopathological characteristics and clinical outcome. Material/Methods Protein levels of vascular endothelial growth factors-A, -C, -D (VEGF-A/-C/-D), their receptors- VEGF-R2 and -R3 (VEGF-R2/-R3), and matrix metalloproteinases 2, -3, and -7 (MMP-2, MMP-3, MMP-7) were quantified in the blood serum samples of 71 patients with UCB before radical cystectomy (RC). Samples of patients with non-invasive UCB or no history of UCB were investigated as controls (n=20). Protein levels in the serum were measured using a flow cytometric cytokine assay. Results A positive association for VEGF-D (p<0.001) and an inverse association for MMP-2 (p=0.017) were observed in patients with positive lymph node (LN) status at the time of RC. VEGF-A (p<0.001), VEGF-C (p<0.001), MMP-2 (p<0.001), and MMP-7 (p=0.005) serum levels were different in serum of patients with invasive UCB compared with non-invasive UCB or healthy individuals. None of the serum markers were associated with disease progression. Conclusions High VEGF-D and low MMP-2 serum levels predict LN metastasis in patients with UCB at the time of RC. VEGF-A, VEGF-C, MMP-2, and MMP-7 serum levels varied significantly between invasive and non-invasive disease as well as in comparison with healthy individuals. Clinical implementation of these marker serum measurements may be valuable to select high-risk patients with more invasive or nodal-positive disease.

Retrograde intrarenal surgery: An expanding role in treatment of urolithiasis

During the past 3 decades, the surgical management of kidney stones has undergone many technological advances and one is the development of the flexible ureteroscopy. The development of this instrument as well as ancillary equipment such as baskets, graspers, and others, and improvements in lithotripsy with Holmium: YAG laser have led to expand its indications with diagnostic and therapeutic management of medical issues of the upper urinary tract such as urolithiasis and urothelial tumors. The objective of this review is to describe its indications and results in the different scenarios for the treatment of urinary stones.

Dusting technique for lithotripsy: what does it mean?

Kidney stones are currently managed using laser lithotripsy and the most recent generation of laser generators have enabled the possibility of the dusting technique. Dusting avoids the use of a basket, as stone fragments are spontaneously evacuated; however, no consensus on the definition of dust currently exists.

Systematic review of ureteral access sheaths: facts and myths

The aim of the present paper was to review the literature on all available ureteral access sheaths (UASs) with their indications, limitations, risks, advantages and disadvantages in current modern endourological practice. Two authors searched Medline, Scopus, Embase and Web of Science databases to identify studies on UASs published in English. No time period restriction was applied. All original articles reporting outcomes or innovations were included. Additional articles identified through references lists were also included. Case reports, editorials, letters, review articles and meeting abstracts were excluded. A total of 754 abstracts were screened, 176 original articles were assessed for eligibility and 83 articles were included in the review. Based on a low level of evidence, UASs increase irrigation flow during flexible ureteroscopy and decrease intrapelvic pressure and probably infectious complications. Data were controversial and sparse on the impact of UASs on multiple reinsertions and withdrawals of a ureteroscope, stone‐free rates, ureteroscope protection or damage, postoperative pain, risk of ureteral strictures, and also on its cost‐effectiveness. Studies on the benefit of UASs in paediatrics and in patients with a coagulopathy were inconclusive. In the absence of good randomized data, the true impact of UASs on surgery outcome remains unclear. The present review may contribute to the evidence‐based decision‐making process at the individual patient level regarding whether or not a UAS should be used.

MP02-02 PURE BIPOLAR PLASMA VAPORIZATION OF THE PROSTATE: 5-YEAR FOLLOW-UP FROM A PROSPECTIVE 3D ULTRASOUND VOLUMETRY STUDY

INTRODUCTION AND OBJECTIVES: Pure bipolar plasma vaporization (BPV) has been established as low-morbidity alternative to conventional transurethral resection of the prostate (TURP). Low intraand postoperative morbidity as well as excellent functional short-term results have been reported. However, long-term outcome is still lacking. The extent of prostate tissue removal, which impacts the durability of postoperative functional improvements, is also unknown after BPV. The aim of the present study was to investigate the long-term functional outcome and associated prostate volume changes following pure BPV of the prostate. METHODS: A consecutive series of 75 patients treated by pure BPV in a tertiary care academic center was prospectively investigated. Prostate volume was assessed using planimetric volumetry following transrectal 3D-ultrasound of the prostate. Prostate volume and clinical parameters were recorded preoperatively and regularly after BPV (after catheter removal, 6W, 6M, 1, 3 and 5Y). RESULTS: Median (interquartile range; IQR) preoperative prostate volume was 41 ml (26.8ml), IPSS 16 (10), QoL 4 (2), Qmax 10.1ml/s (8ml/s), PVR 91ml (140ml) and PSA 2.57ng/ml (3.5ng/ml). A significant relative prostate volume reduction (RVR) of 33.3% (IQR: 22.3%; p<0.001) was already detectable at the time of catheter removal. Relative volume reduction increased significantly up to 12M (6W: 45.9% (17.4%; p<0.001), 6M: 50.5% (16.1%; p<0.001) and 12M 52.2% (17.4%; p1⁄40.014). After 12M the RVR remained stable with 50.6% (14.3%; p1⁄40.58) after 3Y and 52.6% (14.1%; p1⁄40.59) after 5Y. Postoperatively, all investigated clinical parameters improved significantly and remained stable during the 5Y follow-up [5Y results (IQR): IPSS: 3 (8), QoL: 1 (1), Qmax: 16.3ml/s (13.7ml/s), PVR 20ml (46.5ml)]. Median PSA reduction after 5Y was 55% (36.2%). During the observation period 9 urethral strictures (12%) were detected of which 7 were de novo strictures. Bladder neck incisions for postoperative bladder neck stenosis were performed in 6 patients (8%). Median prostate volume in these patients was 30.6ml (18.2ml). Re-resections for regrown adenoma were not necessary. CONCLUSIONS: Low intraand postoperative morbidity in combination with excellent functional outcome and durable prostate volume reduction confirm the role of contemporary BPV as a minimally invasive alternative to conventional TURP. However, postoperative bladder neck stenoses appeared rather frequent after BPV and might be a procedure-specific drawback.

The Potential Therapeutic Usefulness of Targeting BK Polyomavirus inProstate Cancer

Prostate cancer (PCa) is a slow-growing, organ-confined tumor usually accompanied with a favorable overall prognosis. Current standard-of-care chemotherapy, and recently immunotherapies, for patients suffering from this disease may prolong overall survival and improve quality of life, but they do not prevent tumor recurrence and thus are not curative. Underlying reasons are not completely understood. Recent investigations support a possible carcinogenic activity of the human BK polyomavirus (BKPyV) in the prostate. In this commentary, we envisage the development of BKPyV-related therapeutic strategies to be beneficial for individuals at risk of developing PCa.

MP71-19 LOSS OF POWER OUTPUT IS FREQUENTLY DETECTABLE DURING LASER VAPORIZATION OF THE PROSTATE USING THE 180-WATT 532 NM LASER IN COMBINATION WITH MOXYTM LASER FIBERS

INTRODUCTION AND OBJECTIVES: The objective was to measure the penetration depth after PhotoVaporization of the Prostate (PVP) by Enhanced Contrat UltraSonography (ECUS). METHODS: It is a forward-looking study about twelve patients operated by a PVP performed by the GREENLIGHT XPS laser. Ethical committee gave its aproval (EUDRACT N : 2012-001451-39). ECUS was performed (B-mode then contrast mode after injection of 2,4mL of suphur hexafluoride micro bubbles) preoperatively and immediately after the PVP and at 1 month. With ultrasound were measured: width, prostatic volume and diameter of the cavity of vaporization (DC) with the B-mode; then in contrast mode MicroFlow Imaging (MFI): the prostatic width and the NonVascularized cavity diameter (DD). The necrotic depth was measured using the formula: NC 1⁄4 (DD-DC)/2) (Figure 1). RESULTS: The characteristics of the patients were : a median age of 70 years old [57-81], median prostatic volume of 65 cc [40-110], median maximal urinary flow of 7,2 mL/s [2, 9-15,2], median post mictional residual volume of 90 cc [0-213], median IPSS score of 19 [8-24] and a median PSA rate of 4 ng/mL [1,6-7,9]. The results found with ultrasound performed pre and post operatively are summarized in table 1. All the patients had their bladder catheter removed and then discharged the hospital at day 1, except one patient who had an acute retention treated at day 8 by an indwelling catheter. CONCLUSIONS: The use of ECUS showed an unexpected necrotic depth up to 16,5 mm in the immediate post-operative ultrasound. This necrotic depth persisted at 1 month and was measured up to 13 mm. At one month we measured a 26% decrease of the prostatic volume and a 23% of the necrotic depth. These results are to be considered to performe securely PVP without any rectal complication. The continuing follow-up at 6 and 12 months will probably precize the necrotic depth evolution and the potential correlation with the occurrence of irritative voiding dysfunction. Table 1 : Ultrasonography results

MP71-20 ABSORPTION OF IRRIGATION FLUID IS FREQUENTLY DETECTABLE DURING 180W 532-NM LASER VAPORIZATION OF THE PROSTATE: RESULTS FROM A PROSPECTIVE INVESTIGATION USING BREATH ETHANOL MEASUREMENTS

INTRODUCTION AND OBJECTIVES: Laser vaporization (LV) of the prostate using the 532-nm laser is a recommended treatment option for patients with prostatic bladder outlet obstruction and particularly for those with significant cardiovascular comorbidities. Despite the excellent coagulation properties of the laser, fluid absorption was frequently detectable during 120W LV of the prostate. For the nextgeneration 180W laser, a better coagulation technology has been announced. If fluid absorption occurs during LV using this improved but also more powerful laser is unknown. METHODS: Intraoperative fluid absorption was investigated during routine LV using the 180W Greenlight XPS laser (AMS, USA) in 32 consecutive patients. For this purpose intraoperative irrigation was performed using saline containing 1% ethanol. Measurements of breath ethanol were performed every 10 minutes during the operation with a conventional alcometer. The volume of fluid absorption was calculated from these results. Intraoperative changes in hemoglobin (Hb), hematocrit (Hct), venous pH and serum Na, K, Cl, HCO3 were also recorded. Statistical analysis was done using Mann Whitney U test and Wilcoxon signed-rank test. RESULTS: Median age was 73 y (range: 56 85 y), median prostate volume 50 ml (20 99 ml). The median operative time was 60 min (30-150 min), the intraoperative irrigation volume 21 L (6 42 L), and the applied laser energy 175 kJ (70 e 544 kJ). 17 patients (53%) had a positive ethanol test. The median calculated absorption volume in these patients was 827 ml (138 e 4808 ml). In the absorber group, a significant decrease in Hb, Hct, HCO3, pH (p1⁄40.001, 0.004, 0.002 and 0.02, respectively), and a significant increase in serum Cl (p1⁄40.007) were detectable. The changes in Hb, Hct, Cl and HCO3 were significantly greater compared to the non-absorber group (p1⁄40.005, 0.02, 0.001 and 2000ml) were prolonged metabolic acidosis and somnolence, hypothermia, jugular venous distension and significant postoperative weight gain. CONCLUSIONS: Intraoperative fluid absorption occurs in a significant proportion of patients during 180W LV of the prostate. Fluid absorption can be excessive and thus clinically relevant. Early identification of fluid absorption using the ethanol breath test enables timely interventions. If ethanol monitoring is not available, changes in Hb, Hct, pH, HCO3 and Cl can be used to detect potentially dangerous fluid absorption.