Giovanni Battista Di Pierro

Positioning Injury, Rhabdomyolysis, and Serum Creatine Kinase-Concentration Course in Patients Undergoing Robot-Assisted Radical Prostatectomy and Extended Pelvic Lymph Node Dissection

BACKGROUND AND PURPOSE During robot-assisted radical prostatectomy (RARP), patients remain in a steep Trendelenburg position. This can cause positioning injuries as well as rhabdomyolysis. The primary diagnostic indicator of rhabdomyolysis is elevated serum creatine kinase (CK). We investigate whether RARP with extended pelvic lymph node dissection (ePLND) in a prolonged extreme Trendelenburg position can cause positioning injuries and rhabdomyolysis. PATIENTS AND METHODS We performed a prospective study of the first 60 patients undergoing RARP and ePLND for organ-confined prostate cancer at our institute. Positioning injuries were graded according to three degrees of clinical severity. Serum-CK, serum-pH, and base excess (BE) were measured before, during, and for 5 days after surgery. Rhabdomyolysis was defined by serum-CK levels >5000 IU/L. RESULTS Median operative time was 317 minutes (range 200-475 min); median time in the Trendelenburg position was 282 minutes (range 170-470 min). Serum-CK was significantly elevated 6 hours postoperatively, peaking at 18 hours postoperatively. Serum-CK levels did not correlate with pH, BE, and perioperative creatinine values. Serum-CK course shows weak correlation with body mass index (BMI), operative time, Trendelenburg position time, and medium correlation with positioning injuries of any degree. Twenty-one of the 60 (35%) patients showed positioning-related injuries: 16 (27%) patients degree I, 2 (3%) patients degree II, and 3 (5%) patients degree III. Rhabdomyolysis developed in 10 patients. Postoperative renal failure did not develop in any patient receiving postoperative hypervolemic diuretic therapy nor any patient with injuries degrees I, II, or III. conclusion: Clinically relevant positioning injuries and rhabdomyolysis can occur in patients who are subjected to prolonged extreme Trendelenburg position during RARP and ePLND, especially at the beginning of the learning curve. Serum-CK increases significantly after surgery, peaking 18 hours postoperatively. Serum-CK elevation alone is not predictive of positioning injury. By very long operative and Trendelenburg times as well as high BMI with visible position injuries, we recommend serum-CK measurement 6 and 18 hours postoperatively followed by hypervolemic therapy to prevent possible renal injury from rhabdomyolysis if serum-CK >5000 IU/L.

A Prospective Trial Comparing Consecutive Series of Open Retropubic and Robot-Assisted Laparoscopic Radical Prostatectomy in a Centre with a Limited Caseload

BACKGROUND Robot-assisted radical prostatectomy (RALP) is performed worldwide, even in institutions with limited caseloads. However, although the results of large RALP series are available, oncologic and functional outcomes as well as complications from low-caseload centres are lacking. OBJECTIVE To compare perioperative, oncologic, and functional outcomes from two consecutive series of patients with localised prostate cancer treated by retropubic radical prostatectomy (RRP) or recently established RALP in our hospital, which has a limited caseload. DESIGN, SETTING, AND PARTICIPANTS One hundred fifty consecutive patients were enrolled. Their data and outcomes were collected and extensively evaluated. INTERVENTION Seventy-five consecutive patients underwent RRP, and 75 consecutive patients underwent RALP, including all patients of the learning curve. MEASUREMENTS Patient baseline characteristics, perioperative and postoperative outcomes, and complications were evaluated. End points were oncologic data (positive margins, prostate-specific antigen [PSA]), perioperative complications, urinary continence, and erectile function at 3- and 12-mo follow-up. RESULTS AND LIMITATIONS The preoperative parameters from the two groups were comparable. The positive surgical margin (PSM) rates were 32% for RRP and 16% for RALP (p=0.002). For RRP and RALP, the PSA value was <0.2 ng/ml in 91% and 88% of patients 3 mo postoperatively (p=0.708) and in 87% and 89% of patients 12 mo postoperatively (p=0.36), respectively. Continence rates for RRP and RALP were 83% and 95% at 3-mo follow-up (p=0.003) and 80% and 89% after 12-mo follow-up (p=0.092), respectively. Among patients who were potent without phosphodiesterase type 5 inhibitors (PDE5-I) before RRP and RALP, recovery of erectile function with and without PDE5-Is was achieved in 25% (12 of 49 patients) and 68% (25 of 37 patients) 3 mo postoperatively (p=0.009) and in 26% (12 of 47 patients) and 55% (12 of 22 patients) 12 mo postoperatively (p=0.009), respectively. Minimal follow-up for RRP was 12 mo; median follow-up for the RALP group was 12 mo (range: 3-12). According to the modified Clavien system, major complication rates for RRP and RALP were 28% and 7% (p=0.025), respectively; minor complication rates were 24% and 35% (p=0.744), respectively. CONCLUSIONS Despite a limited caseload and including the learning curve, RALP offers slightly better results than RRP in terms of PSM, major complications, urinary continence, and erectile function.

Early Recovery of Urinary Continence After Radical Prostatectomy Using Early Pelvic Floor Electrical Stimulation and Biofeedback Associated Treatment

PURPOSE We analyzed the benefit of the early combined use of functional pelvic floor electrical stimulation and biofeedback in terms of time to recovery and rate of continence after radical prostatectomy. MATERIALS AND METHODS A total of 60 consecutive patients who underwent radical prostatectomy were included in the study. Patients were prospectively randomized to a treatment group (group 1) vs a control group (group 2). In group 1 a program of pelvic floor electrical stimulation plus biofeedback began 7 days after catheter removal, twice a week for 6 weeks. Each of the 12 treatment sessions was composed of biofeedback (15 minutes) followed by pelvic floor electrical stimulation (20 minutes). The evaluation of continence was performed at time 0, at 2 and 4 weeks, and at 2, 3, 4, 5 and 6 months during followup. Evaluations were performed using the 24-hour pad test and the incontinence section of the International Continence Society questionnaire. RESULTS The mean leakage weight became significantly lower (p <0.05) in group 1 than in group 2 starting at 4 weeks until 6 months of followup. A significant difference (p <0.05) between groups 1 and 2 in terms of percentage of continent patients was achieved from 4 weeks (63.3% group 1 and 30.0% group 2) to 6 months (96.7% group 1 and 66.7% group 2). CONCLUSIONS Early, noninvasive physical treatment with biofeedback and pelvic floor electrical stimulation has a significant positive impact on the early recovery of urinary continence after radical prostatectomy.

Modern extraction techniques and their impact on the pharmacological profile of Serenoa repens extracts for the treatment of lower urinary tract symptoms

BackgroundBioactive compounds from plants (i.e., Serenoa repens) are often used in medicine in the treatment of several pathologies, among which benign prostatic hyperplasia (BPH) associated to lower urinary tract symptoms (LUTS).DiscussionThere are different techniques of extraction, also used in combination, with the aim of enhancing the amount of the target molecules, gaining time and reducing waste of solvents. However, the qualitative and quantitative composition of the bioactives depends on the extractive process, and so the brands of the recovered products from the same plant are different in terms of clinical efficacy (no product interchangeability among different commercial brands).SummaryIn this review, we report on several and recent extraction techniques and their impact on the composition/biological activity of S. repens-based available products.

Standardized and Simplified Extended Pelvic Lymph Node Dissection During Robot-assisted Radical Prostatectomy: The Monoblock Technique

OBJECTIVE To describe a simplified technique of extended pelvic lymph node dissection (ePLND) for prostate cancer treated by robot-assisted radical prostatectomy (RARP). MATERIALS AND METHODS The technique uses a standardized 10-step procedure to obtain a single tissue monoblock from each side that contains all lymph nodes within the ePLND template. We performed a prospective study of all patients with prostate cancer (n = 134) with a preoperative Gleason score of ≥ 7 and/or prostate-specific antigen level >10 ng/mL undergoing ePLND before RARP using transperitoneal access at our institute from July 2008 to August 2011. The standardized procedure consisted of 10 distinct surgical steps. Dissection obtained all lymph nodes and surrounding fatty tissue in a single monoblock applying the following ePLND template: cranially, the ureter crossing the common iliac artery; caudally, the femoral canal; laterally, the medial border of the external iliac artery; and medially, the medial border of the hypogastric artery. The number of resected lymph nodes and postoperative ePLND-related complications according to the modified Clavien classification were documented. RESULTS The median number of resected lymph nodes was 14 (interquartile range 11-19). Complications related to ePLND were seen in 8 patients (5.9%). CONCLUSION The robot-assisted monoblock ePLND technique is simple to perform, offers a good overview of the operative field during the entire procedure, permits complete and radical removal of the lymphatic tissue contained in the ePLND template, and avoids spreading of fatty and lymphatic tissue within the abdominal cavity.

Extended pelvic lymphadenectomy and various radical prostatectomy techniques: is pelvic drainage necessary?

The occurence of lymphoceles in patients after radical prostatectomy is well known (2–10%). It appears that patients undergoing open extraperitoneal radical prostatectomy develop more lymphoceles than patients undergoing robot‐assisted radical prostatectomy with transperitoneal access. The present study investigates in a prospective randomized manner whether the time of drainage (1 vs 7 days) makes a difference or whether drainage is even necessary. The study data, collected in the same institution, are compared with the incidence of lymphocele in patients treated by robot‐assisted radical prostatectomy.

Bladder Cancer: A Simple Model Becomes Complex

Bladder cancer is one of the most frequent malignancies in developed countries and it is also characterized by a high number of recurrences. Despite this, several authors in the past reported that only two altered molecular pathways may genetically explain all cases of bladder cancer: one involving the FGFR3 gene, and the other involving the TP53 gene. Mutations in any of these two genes are usually predictive of the malignancy final outcome. This cancer may also be further classified as low-grade tumors, which is always papillary and in most cases superficial, and high-grade tumors, not necessarily papillary and often invasive. This simple way of considering this pathology has strongly changed in the last few years, with the development of genome-wide studies on expression profiling and the discovery of small non-coding RNA affecting gene expression. An easy search in the OMIM (On-line Mendelian Inheritance in Man) database using “bladder cancer” as a query reveals that genes in some way connected to this pathology are approximately 150, and some authors report that altered gene expression (up- or down-regulation) in this disease may involve up to 500 coding sequences for low-grade tumors and up to 2300 for high-grade tumors. In many clinical cases, mutations inside the coding sequences of the above mentioned two genes were not found, but their expression changed; this indicates that also epigenetic modifications may play an important role in its development. Indeed, several reports were published about genome-wide methylation in these neoplastic tissues, and an increasing number of small non-coding RNA are either up- or down-regulated in bladder cancer, indicating that impaired gene expression may also pass through these metabolic pathways. Taken together, these data reveal that bladder cancer is far to be considered a simple model of malignancy. In the present review, we summarize recent progress in the genome-wide analysis of bladder cancer, and analyse non-genetic, genetic and epigenetic factors causing extensive gene mis-regulation in malignant cells.

Current and emerging strategies in bladder cancer.

Urothelial cell carcinoma is one of the most common malignancies of the urinary tract. The standard of care, intravesical chemo- and immunotherapy, while effective, is associated with a considerable side-effect profile and approximately 30% of patients either fail to respond to treatment or suffer recurrent disease within 5 years. In the setting of muscle-invasive urothelial carcinoma, use of neoadjuvant chemotherapy is associated with overall survival benefit. Muscle invasive bladder cancer is life threatening, showing modest chemosensitivity, and usually requires radical cystectomy. Although bladder cancer is fairly well-genetically characterized, clinical trials with molecularly targeted agents have, in comparison to other solid tumors, been few in number and largely unsuccessful. Hence, bladder cancer represents a considerable opportunity and challenge for alternative therapies. In this review, we will focus on promising global or pathway-based approaches (epigenetic modulators, kinase inhibitors, angiogenesis blockage, peroxisome proliferator-activated receptor γ agonists, apoptosis inductors, virus therapy) supported by a deeper understanding of molecular biology of urothelial carcinoma, which have been recently tested in clinical trials.

Male Urethral Strictures: A National Survey Among Urologists in Italy

OBJECTIVE To determine national practice patterns in the management of male urethral strictures among Italian urologists. METHODS We conducted a survey using a nonvalidated questionnaire mailed to 700 randomly selected Italian urologists. Data were registered into a database and extensively evaluated. Analysis was performed using SAS statistical software (version 9.2). Statistical significance was defined as P ≤.05. RESULTS A total of 523 (74.7%) urologists completed the questionnaire. Internal urethrotomy and dilatation were the most frequently used procedures (practiced by 81.8% and 62.5% of responders, respectively), even if most urologists (71.5%) considered internal urethrotomy appropriate only for strictures no longer than 1.5 cm; 12% of urologists declared to use stents. Overall, minimally invasive techniques were performed more frequently that any open urethroplasty (P = .012). Particularly, 60.8% of urologists did not perform urethroplasty surgery, 30.8% performed 1-5 urethroplasties yearly, and only 8.4% performed >5 urethroplasty surgeries yearly. The most common urethroplasty surgery was one-stage graft technique, particularly using oral mucosa and ventrally placed. Diagnostic workup and outcome assessment varied greatly. CONCLUSION In Italy, minimally invasive procedures are the most commonly used treatment for urethral stricture disease. Only a minimal part of urologists perform urethroplasty surgery and only few cases per year. The most preferred techniques are not traditional anastomotic procedures but graft urethroplasties using oral mucosa; the graft is preferably ventrally placed rather than dorsally. There is no uniformity in the methods used to evaluate urethral stricture before and after treatment.

Prospective Randomized Trial Comparing Titanium Clips to Bipolar Coagulation in Sealing Lymphatic Vessels During Pelvic Lymph Node Dissection at the Time of Robot-assisted Radical Prostatectomy

Lymphocele is the most common complication after pelvic lymph node dissection (PLND). Over the years, various techniques have been introduced to prevent lymphocele, but no final conclusion can be drawn regarding the superiority of one technique over another. In this prospective study, 220 patients undergoing robot-assisted radical prostatectomy between 2012 and 2015 were randomized to receive titanium clips (group A, n=110) or bipolar coagulation (group B, n=110) to seal lymphatic vessels at the level of the femoral canal during extended PLND (ePLND). Ultrasound examination was used to detect lymphoceles at 10 and 90 d after surgery. Lymphocele was defined as any clearly definable fluid collection and was considered clinically significant when requiring treatment. There were no statistically significant differences between groups A and B regarding overall lymphocele incidence (47% vs 48%; difference -0.91%, 95% confidence interval [CI] -2.6 to 0.7; p=0.9) and the rate of clinically significant lymphocele [5% vs 4%; difference 0.75%, 95% CI, 0.1-3.2; p=0.7]. The two groups were comparable regarding mean (±SD) lymphocele volume (30±32 vs 35±39ml; p=0.6), lymphocele location (unilateral, 37% vs 35%, p=0.7; bilateral, 13% vs 14%, p=0.9), and time to lymphocele diagnosis (95% vs 98% on postoperative day 10; p=0.5). In conclusion, this trial failed to identify a difference in lymphocele occurrence between clipping and coagulation of the lymphatic vessels at the level of the femoral canal during robot-assisted ePLND for prostate cancer. PATIENT SUMMARY In this study we compared the frequency of postoperative complications after sealing lymphatic vessels from the leg to the abdomen using metallic clips or electrical coagulation during robot-assisted surgery for prostate cancer. We found no difference in postoperative complications between the two methods.