Inosine monophosphate dehydrogenase type 2 polymorphism IMPDH2 3757T>C (rs11706052) and 12-month evolution of the graft function in renal transplant recipients on mycophenolate-based immunosuppression.

Variant allele at the inosine monophosphate dehydrogenase type 2 polymorphism IMPDH2 3757T>C has been associated with increased enzyme activity and reduced susceptibility to mycophenolic acid (MPA) in vitro. It has been suggested associated with an increased risk of acute rejection in renal transplant recipients on MPA-based immunosuppression, but not unambiguously. We assessed one-year evolution of the estimated glomerular filtration rate (eGFR) in transplanted variant allele carriers and wild-type subjects, while controlling for a number of demographic, pharmacogenetic, (co)morbidity, and treatment baseline and time-varying covariates. The eGFR slopes to day 28 (GMR = 1.01, 95% CI 0.93-1.09), and between days 28 and 365 (GMR = 1.01, 95% CI 0.99-1.02) were practically identical in 52 variant carriers and 202 wild-type controls. The estimates (95%CIs) remained within the limits of ±20% difference even after adjustment for a strong hypothetical effect of unmeasured confounders. Polymorphism IMPDH2 3757T>C does not affect the renal graft function over the 1st year after transplantation.

The stress for surgeons: exploring stress entities with the robotic senhance surgical system.

Robotic surgery is on its way to revolutionizing traditional surgical procedures, offering precise and minimally invasive techniques hypothesized to shorten recovery times and improve patient outcomes. While there have been multiple publications on robotic systems' medical and procedural achievements, more emphasis should be put on the surgeon's experience, especially in comparison with laparoscopic surgery. The present report aims to systematically examine the stress impact on surgeons by comparing the robotic Senhance Surgical System (Asensus Surgical, Durham, North Carolina, U.S.A) to laparoscopic surgery. The well-established "SURG-TLX" survey is used to measure distinct stress entities. The "SURG-TLX" survey is a modified version of the NASA-TLX, validated for surgery by M. Willson. Based on a comprehensive database from six centers encompassing various disciplines and surgical procedures, our analysis indicates significantly reduced "overall stress" levels for robotic (cockpit) compared to laparoscopic surgeons. Exploring the "SURG-TLX" stress dimensions further between methods (robotic vs. laparoscopic) and surgeon position (laparoscopic, (robotic) bedside, or (robotic) cockpit) resulted in significantly more Mental (p.value < 0.015), less Physical Demands (p.value < 0.001) and less Distraction (p.value < 0.009) for robotic surgery, especially regarding the robotic cockpit surgeons. This finding suggests that robotic surgery with the Senhance Surgical System contributes to a favorable stress profile for surgeons, potentially enhancing their overall well-being and performance.

Robotic-assisted radical prostatectomy: a multicenter experience with the Senhance Surgical System.

PURPOSE: Robotic-assisted surgery for radical prostatectomy is becoming a standard treatment, and respective implementations are expanding. The Senhance Surgical System is a robotic system with existing but limited data on radical prostatectomy, including a lack of multicenter study experiences. The TRUST study aims to fill this gap and explores observations for radical prostatectomy with the Senhance Surgical System. METHODS: Between August 2019 and November 2022, 375 patients met inclusion criteria from two European sites. Patients' surgical procedure times, data on conversion, malfunction, adverse events, and pain scores were registered and evaluated. Outcomes were calculated for both sides, combined as a total and compared between the initial (1st-150th case) and later (> 150th case) period. RESULTS: The median operating time was 190 min (IQR: 167.5-215.0) and the median docking time was 3 min (IQR: 2.0-5.0). Eighteen cases (4.8%) were converted to standard laparoscopy and two (0.5%) to open. Two perioperative (0.5%) and eleven postoperative adverse events (2.9%) occurred, mostly (83.3%) categorized as mild. Pain scores were reduced from an average of 3.4 (± 1.4) on the postoperative day to 0.9 (± 0.7) at discharge. Compared to our previous data and based on a comparison between our initial and later period, operating time seems to plateau. However, docking time, complication, and conversion rates were successfully reduced. CONCLUSION: We demonstrate progressing safety and efficiency for robotic-assisted radical prostatectomy with the Senhance Surgical System.

Senhance robotic radical prostatectomy: A single-centre, 3-year experience.

BACKGROUND: Senhance Surgical System is a novel robotic platform used in University Hospital Centre Zagreb since February 2019. In this study, we present our 3-year experience with this platform. PATIENTS AND METHODS: Data were prospectively collected for 200 patients who underwent extraperitoneal robotic radical prostatectomy (RRP) from May 2019 to March 2022. RESULTS: The median age of the patients was 65 years, and the prostate-specific antigen was 6.9 ng/mL. Clinically, most of the patients had T1c stage. The estimated blood loss was 250 mL, and there were 6 conversions to laparoscopic and 2 to open prostatectomy. There were 15 early postoperative complications, 11 Clavien-Dindo classification grade I, 3 grade II and 1 grade IV. Functional outcomes in the first 150 patients: 140 patients (93.3%) had good urinary control. Thirteen patients underwent additional oncological treatment. CONCLUSION: RRP performed with the Senhance robotic platform is a feasible and safe procedure with good initial results.

Loss of Function ABCG2 c.421C>A (rs2231142) Polymorphism Increases Steady-State Exposure to Mycophenolic Acid in Stable Renal Transplant Recipients: An Exploratory Matched Cohort Study.

INTRODUCTION: Polymorphism ABCG2 c.421C>A (rs2231142) results in reduced activity of the important drug efflux transporter breast cancer-resistance protein (BCRP/ABCG2). One study has suggested that it may affect enterohepatic recirculation of mycophenolic acid (MPA). We evaluated the effect of rs2231142 on steady-state exposure to MPA in renal transplant recipients. METHODS: Consecutive, stable adult (age ≥ 16 years) renal transplant recipients on standard MPA-based immunosuppressant protocols (N = 68; 43 co-treated with cyclosporine, 25 with tacrolimus) underwent routine therapeutic drug monitoring after a week of initial treatment, and were genotyped for ABCG2 c.421C>A and 11 polymorphisms in genes encoding enzymes and transporters implicated in MPA pharmacokinetics. ABCG2 c.421C>A variant versus wild-type (wt) patients were matched with respect to demographic, biopharmaceutic, and genetic variables (full optimal combined with exact matching) and compared for dose-adjusted steady-state MPA pharmacokinetics [frequentist and Bayes (skeptical neutral prior) estimates of geometric means ratios, GMR]. RESULTS: Raw data (12 variant versus 56 wt patients) indicated around 40% higher total exposure (frequentist GMR = 1.45, 95% CI 1.10-1.91; Bayes = 1.38, 95% CrI 1.07-1.81) and around 30% lower total body clearance (frequentist GMR = 0.66, 0.58-0.90; Bayes = 0.71, 0.53-0.95) in variant carriers than in wt controls. The estimates were similar in matched data (11 variant versus 43 wt patients): exposure GMR = 1.41 (1.11-1.79) frequentist, 1.39 (1.15-1.81) Bayes, with 90.7% and 85.5% probability of GMR > 1.20, respectively; clearance GMR = 0.73 (0.58-0.93) frequentist, 0.71 (0.54-0.95) Bayes. Sensitivity analysis indicated low susceptibility of the estimates to unmeasured confounding. CONCLUSIONS: Loss-off-function polymorphism ABCG2 c.421C>A increases steady-state exposure to MPA in stable renal transplant patients.

Senhance robot-assisted adrenalectomy: a case series.

We present a case series of 12 consecutive robot-assisted adrenalectomies performed from May 2019 to March 2020 by a single surgeon experienced in laparoscopy using the novel Senhance robotic system. Eleven patients had primary aldosteronism due to an adrenal adenoma, diagnosed by means of endocrinological and radiological evaluation, and 1 had a benign adrenal cyst. The robotic adrenalectomy technique is described in detail. The mean procedure time was 165.1 minutes, with robotic docking time of 11.6 minutes and console time of 98.6 minutes. The mean estimated blood loss was 47 mL, and hospital stay duration was 4.5 days. There was 1 Clavien Dindo IIIB complication and 1 patient underwent conversion to laparoscopy. All patients with adenoma had complete biochemical remission after surgery. In conclusion, the Senhance robotic system is a safe and feasible platform for benign adrenal surgery in high-volume centers.

Correction to: Letter to the editor on "Initial experience of laparoscopic radical nephrectomy using the Senhance® robotic system for renal cell carcinoma".

[This corrects the article DOI: 10.1007/s13691-021-00494-y.].

LAPAROSCOPIC RADICAL PROSTATECTOMY: SINGLE CENTER CASE SERIES.

Laparoscopic radical prostatectomy (LRP) is traditionally characterized as a technically difficult procedure with a long learning curve but it is successfully performed worldwide. The aim of this paper was to assess the initial learning curve and clinical outcomes for LRP in our center. We performed a retrospective study including 63 LRP cases, in the course of 22 months, performed by 2 urologists, with no previous LRP experience. All patients were previously assessed by a multidisciplinary team and were selected on the basis of low and intermediate risk disease attributes according to the classification of prostate cancer risk groups of the European Association of Urology. The main outcomes of follow-up are procedure duration, estimated blood loss, complications, positive surgical margins, biochemical relapse and urinary continence. The median follow-up was 19.6 months. The median procedure duration was 196.8 minutes and median blood loss 257.1 mL. Significant decrease in both outcomes was observed when comparing first and last cases in the series. There were 5 (7.9%) Clavien Dindo grade II complications. Undetectable prostate specific antigen (PSA) was observed in 59 (93.6%) patients, and fifty-five patients (87.3%) were continent. Following a methodical learning approach, LRP can be safely mastered with favorable outcomes.

PELVIC REHABILITATION FOR URINARY INCONTINENCE AFTER RADICAL PROSTATECTOMY.

Radical prostatectomy (RP) performed by open, laparoscopic, or robotic approach is considered the gold standard for localized prostate cancer (PCa). However, it carries the risk of postprostatectomy urinary incontinence (UI) and erectile dysfunction (ED) which significantly reduce patients' satisfaction with surgery and quality of life (QoL), therefore it is important to decrease the possibility or severity of these complications to a minimum. There are several preoperative prognostic factors such as urethral length and closing pressure obtained by magnetic resonance imaging and profilometry, as well as several variations in the surgical approach such as preservation of the neurovascular bundle (NVB) and puboprostatic ligaments, sparing or reconstruction of bladder neck, Retzius-sparing approach, and meticulous surgical dissection, used to predict or prevent unwanted side effects of RP. In addition, there are postoperative methods that can help reduce complications. In this review, we will present the role of pelvic rehabilitation with an emphasis on pelvic floor muscle training (PFMT) in reducing consequences of radical surgery.

SENHANCE ROBOTIC RADICAL PROSTATECTOMY.

Since its introduction 20 years ago, robotic radical prostatectomy has become a standard of care in the treatment of localized prostate cancer in many Centers. Until recently, they have all been performed by the only available robotic platform. Senhance is a novel robotic platform that was approved for clinical use. The term Senhance was used to systematically search PubMed and Scopus databases for relevant articles that were afterward filtered for appropriate designs and data reports. There were two reports that met all of the criteria and were included in the review. Both studies were designed as prospective case series with a total of 234 patients where the data including operative data and oncological outcomes were reported. The average operative time ranged between 180 and 195 min, with estimated blood loss between 250 and 300 mL. There was 3 Clavien - Dindo grade III, and 1 Clavien - DIndo grade IV complication reported. One of the studies compared it with laparoscopy, but no significant difference in operative time and blood loss was found. Both studies concluded that the Senhance is a feasible and safe robotic platform for radical prostatectomy.

Comparison of extraperitoneal laparoscopic and extraperitoneal Senhance radical prostatectomy.

BACKGROUND: Senhance is novel robotic platform which can be used to perform radical prostatectomy (RP). We compare our results of robotic RP to similar patients operated with laparoscopic technique. PATIENTS AND METHODS: A prospective study of 61 patients operated laparoscopically and 107 patients operated using the Senhance robotic system. We have analysed operative and postoperative results in both groups. RESULTS: There was no difference in the operative time, estimated blood loss, positive surgical margins, length of hospitalisation and catheterisation. There were 4 (6.5%) Clavien-Dindo grade I complications, and 5 (8.1%) late complications in laparoscopy. There were 6 (5.6%) Clavien-Dindo grade I, 3 (2.8%) grade II, 1 (0.9%) grade IV complications and 2 (1.9%) late complications in robotic group. CONCLUSION: Senhance robot-assisted RP is safe, feasible and offers good and comparable functional and oncological outcomes to laparoscopy. The transition to robotic surgery with a relatively fast learning curve can be done effectively for surgeons with previous laparoscopic experience.

Resistant hypertension after renal infarction in a man with fibromuscular dysplasia.

We report the case of 39-year-old Caucasian man presenting in emergency department with new onset of severe hypertension with hypokalaemia eight weeks after renal colic. Patient was referred to a hypertension unit for further investigation. Hormonal analysis confirmed secondary aldosteronism and slightly impaired kidney function. Imaging revealed smaller right kidney, 'string of beads appearance' of distal part of right renal artery, a short zone of dissection and renal infarction. Renal scintigraphy showed significant blood flow reduction and severe functional damage of the right kidney. Despite multidrug antihypertensive treatment patient's hypertension was resistant and target organ damage evolved. After initial patient's refusal, he was later successfully treated with laparoscopic simple nephrectomy. Histopathological analysis confirmed renal artery dissection and medial fibroplasia. Thereafter, hypertension was controlled with trandalopril monotherapy. This is a first case report of the patient with renovascular multifocal fibromuscular dysplasia, dissection and renal infarction whose diagnosis of the disease was confirmed by angiography and histopathologic analysis. Resistant hypertension was successfully treated with nephrectomy.

Upper urinary tract surgery and radical prostatectomy with Senhance® robotic system: Single center experience-First 100 cases.

BACKGROUND: The Senhance® robotic surgery system is a novel robotic platform used in several European and World centres. We present our experience in urologic surgery using this platform. PATIENTS AND METHODS: From May 2019 to December 2020, we performed 30 operations of upper urinary tract (UUT) and 70 extraperitoneal radical robotic prostatectomies (RRP). Relevant data were prospectively collected for key outcomes. RESULTS: The median age for UUT was 51, and for RRP 65 years. The average estimated blood loss for UUT was 30, and for RRP 200 ml. The average operating time for UUT was 160, and for RRP 200 min. In-hospital stay for UUT was on average 4, and for RRP 5 days. In UUT group, one patient had Clavien-Dindo complication grade II and one had IIIb. In RRP, three patients had grade I complications and three patients had grade II complications. Catheter was removed on average 8 days after RRP. CONCLUSION: The Senhance® robotic system is a safe and feasible approach to urological surge.

Emergency Ilio-femoral Bypass during Kidney Transplantation due to External Iliac Artery Dissection: Case Report.

Intraoperative iliac artery dissection during kidney transplantation is a rare but serious complication that requires prompt intervention. We present a case of right external iliac artery dissection during deceased donor kidney transplantation. A 57-year-old male patient underwent standard pretransplant evaluation and had no signs of either significant aortoiliac occlusive disease or peripheral arterial occlusive disease. Diabetic nephropathy, arterial hypertension and smoking were the underlying causes of the patient's end-stage renal disease. Transplantation was performed in the standard fashion. The kidney was positioned in the right iliac fossa and the venous end to-side anastomosis was performed first. A significant dissection of the right external iliac artery was found on arteriotomy. Immediate ilio-femoral bypass with a vascular prosthesis was performed. During two years of follow-up the kidney function is stable and there are no signs of lower limb vascular insufficiency.

OCT4 immunohistochemistry after staging laparoscopic retroperitoneal lymphadenectomy for testicular tumor.

Twenty to thirty percent of patients with clinical stage I testicular tumor have metastases in the retroperitoneum. The aim of this study was to evaluate the role of OCT4 immunohistochemistry in histopathologic diagnosis of lymph node metastases in patients with nonseminomatous germ cell testicular tumors. All clinical stage I patients with staging laparoscopic retroperitoneal lymphadenectomy from 2001 until 2009 were included. Archived materials of dissected lymph nodes were reassessed and additional immunohistochemical staining with OCT4 antibody was performed in patients diagnosed as free from metastases. Each slide was visually estimated for the percentage of tumor cells showing nuclear immunoreactivity for OCT4. The study included 93 patients, of which 30 (32.3%) had initially positive retroperitoneal lymph nodes. Of the remaining 63 patients, materials were missing for 5 patients, so additional immunohistochemical staining was performed in 58 patients. Of these, two (3.4%) patients were OCT4 positive, suggesting a conclusion that they were initially misdiagnosed as stage I and metastasis free. OCT4 proved its value in detecting retroperitoneal metastases. Staging laparoscopic retroperitoneal lymphadenectomy for nonseminomatous germ cell testicular tumors in clinical stage I is a reasonable option for selected patients.

The association of preoperative reduced glomerular filtration rate with higher staging and histology grades in patients with urinary tract cancers.

PURPOSE: Studies have shown the increased incidence of urinary tract cancers which are associated with a decrease in glomerular filtration rate (GFR). We hypothesized that patients with GFR < 60 ml/min/1.73 m2 have an increased risk for higher staging and histology grades of cancers and, therefore, the increased risk for cancer recurrence and cancer-related death. METHODS: Retrospective clinical data and pathology reports were completed for 2116 patients. Patients were divided into two subgroups regarding GFR; the first group with GFR < 60 ml/min/1.73 m2 and the second group with GFR > 60 ml/min/1.73 m2 and regarding cancer recurrence. Cancers were also divided by stages (1-4) according to TNM classification. Patients were followed-up during 3 years. RESULTS: We have found significantly higher number of cancers with higher histology grades and higher staging in group of patients with GFR < 60 ml/min/1.73 m2 in all urinary tract localizations. GFR was the strongest predictor for higher cancer histology grade and only significant predictor for higher cancer staging. Patients with GFR < 60 ml/min/1.73 m2 had OR for higher histology grade, higher staging, and cancer recurrence of 10.7, 5.3, and 11.3 compared to patients with GFR > 60 ml/min. CONCLUSIONS: Higher staging and histology grades in patients with urinary tract cancers are associated with reduced GFR. Reduced GFR in these patients is a risk factor for cancer recurrence and cancer-related survival. Possible involvement of uremic toxins must be taken into account especially when cancers are predominantly located in estrogen sensitive organs. These patients should be intensively monitored and probably be more aggressively treated.

THE PROSTATE CENTER: MULTIDISCIPLINARITY, ORGANIZATION OF DIAGNOSTIC WORK-UP AND TREATMENT OF PROSTATE CANCER.

The aim of this paper is to show the results of prostate cancer treatment in Prostate Center of Department of Urology at the University Hospital Center Zagreb. The answer to growing demands for prostate cancer treatment due to increasing incidence is the formation of specialized, multidisciplinary units/centers that deal mainly with prostate cancer. The need was recognized by European School of Oncology and European Association of Urology, who have proposed their concepts of validating such centers with the aim of promoting high-quality prostate cancer treatment. Following these trends, the Department of Urology at the University Hospital Center Zagreb has established the Prostate Center. This new unit offers specialized and individualized approach to workup, treatment and follow up for prostate cancer patients based on multidisciplinarity. The Prostate Center was also established as a platform for education and research.