The reduced function allele SLCO1B1 c.521T>C is of no practical relevance for the renal graft function over the first post-transplant year in patients treated with mycophenolic acid.

OBJECTIVE: It is unclear whether renal transplant recipients treated with mycophenolic acid (MPA) who carry the reduced-function allele at polymorphism SLCO1B1 c.521T>C differ from their wild-type peers regarding renal outcomes and tolerability. We aimed to estimate the effect of this polymorphism on the graft function (estimated glomerular filtration rate, eGFR) over the first 12 post-transplant months in patients on MPA-based maintenance immunosuppression. METHODS: In a 12-month observational cohort study, consecutive adult patients were repeatedly assessed for eGFR. The SLCO1B1 c.521C>T variant allele carriers (exposed) and wild-type subjects (controls) were balanced on a range of demographic, medical, and genetic variables at baseline, and eGFR trajectory was estimated with further adjustment for time-varying covariates. A subset of patients were assessed for exposure to MPA 5-7 days after the transplantation. RESULTS: The adjusted eGFR slopes from day 1 to day 28 (daily), and from day 28 to day 365 (monthly) were practically identical in exposed (n = 86) and control (n = 168) patients [geometric means ratios (GMR) = 0.99, 95% confidence interval (CI) = 0.92-1.06 and GMR = 0.98, 0.94-1.01, respectively]. The rates of adverse renal outcomes and possible MPA-related adverse effects were low, and similar in exposed and controls [rate ratios (RR) = 0.94, 0.49-1.84 and RR = 1.08, 0.74-1.58, respectively]. The pharmacokinetic analysis did not signal meaningful differences regarding exposure to MPA, overall (exposed n = 23, control n = 45), if cotreated with cyclosporine (n = 17 vs. n = 26) or with tacrolimus (n = 8 vs. n = 17). CONCLUSIONS: In patients treated with MPA, variant allele SLCO1B1 c.521T>C appears of no practical relevance regarding the 12-month renal graft function, MPA safety and exposure to MPA at early steady-state.

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.

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.

FLEXIBLE URETERORENOSCOPY AND LASER LITHOTRIPSY IN A PATIENT WITH A STONE IN THE TRANSPLANTED KIDNEY: A CASE REPORT.

We report a case of a 31-year-old patient with obstructive ureterolithiasis in a transplanted kidney, treated endoscopically with flexible ureterorenoscopy and laser lithotripsy. The patient presented with biochemical signs of acute renal failure and ultrasonographically detected hydronephrosis. Emergency nonenhanced computed tomography scan revealed an obstructive 5-mm stone in the ureter of the transplanted kidney with resulting hydronephrosis. The patient received a double J stent to relieve allograft obstruction. Since the stone size was deemed favorable for conservative treatment, the patient was discharged. Two months later, he was readmitted for leucopenia caused by mycophenolate mofetil. After recuperation of his white blood cell count, he was referred to extracorporeal shock wave lithotripsy, but since the stone was radiolucent, an endoscopic procedure was indicated. Retrograde endoscopic flexible ureterorenoscopy with 'dusting' of the stone was successfully performed. One year after the procedure, the patient was stone free and with good allograft function.

LAPAROSCOPIC ADRENAL-SPARING SURGERY CASE SERIES: PARTIAL ADRENALECTOMY AND CYST RESECTION.

The aim is to present our case series documenting indications, laparoscopic technique, surgical and endocrinologic outcomes of laparoscopic partial adrenalectomy. In the period from April 2011 until October 2021, we performed 39 procedures. The patients were divided into three groups: unilateral adrenal gland tumor with a normal contralateral gland (group 1), tumor of the solitary adrenal gland (group 2), and adrenal cysts (group 3). There were 20 patients in group 1, 6 patients in group 2, and 13 patients in group 3. The most common histology in group 1 was adenoma (40%), all tumors in group 2 were renal cell carcinoma metastases, and all cysts in group 3 were benign. There were no major complications (Clavien Dindo grade ≥2) in the whole cohort. All patients in groups 1 and 3 had favorable endocrinologic outcomes, and 50% of group 2 patients required lifelong hydrocortisone replacement therapy. The procedure is safe and feasible with favorable outcomes in the hands of a high volume adrenal surgeon.

OPEN RADICAL CYSTECTOMY: SINGLE CENTER RESULTS AND OUTCOMES IN THE LAST FIVE YEARS.

Radical cystectomy is a therapeutic modality of choice for many patients with muscle-invasive bladder cancer. We conducted a retrospective study of open radical cystectomies performed at a single Center from January 2017 to January 2022. Decision on the urinary diversion type was based on tumor stage, comorbidities, patient age, general condition and preferences. There were 19.5% of female and 80.5% of male patients, median age 67 (range 38-90) years. We performed 96 (44.7%) ureterocutaneostomies (UCS), 67 (31.2%) ileal conduit derivations, and 52 (24.2%) orthotopic neobladder derivations (OND). There were 17 (7.9%) complications after UCS, 7 (3.2%) after incontinent urinary diversion, and 7 (3.2%) after OND. Fifty-five (25.6%) patients developed early complications, of which 31 (14.4%) during the initial hospitalization period, and 24 (11.2%) required re-hospitalization in the 30-day postoperative period. The most common wound-related complication was wound dehiscence, most typically caused by infection. The main reason for readmission was urosepsis. The 30-day mortality rate was 0.9%. Late complications that occurred 30 days after the operation were found in 39 (18.1%) cases. Bladder cancer is a high-mortality disease that requires a multidisciplinary and personalized approach. Further development of multidisciplinary teams, perioperative and postoperative care, and follow-up strategy is needed to improve the oncologic and functional outcomes of this procedure.

POSTPROSTATECTOMY CONTINENCE AFTER FUNCTIONAL MAGNETIC PELVIC STIMULATION.

Although radical prostatectomy is considered the gold standard for optimal treatment of localized prostate cancer, this radical surgery carries a significant risk of erectile dysfunction and urinary incontinence which can be present as transient or permanent side effects in many patients. We have made significant advances in diagnostic and surgical approach to prostate cancer, using a number of new methods that are becoming increasingly available, resulting in better treatment outcomes. However, we still do not use all the possibilities for the prevention and treatment of these side effects, probably due to their insufficient research, or unclear effectiveness. Functional magnetic stimulation is a method used to treat a large number of diseases, i.e., to alleviate their symptoms and ailments. Its role through pelvic stimulation has been proven in the treatment of incontinence in women, and in our study, we want to determine its role in more detail, primarily in the treatment of urinary incontinence in patients after prostate cancer surgery. In case of positive results, this method may be recommended for wider use in patients with adverse effects of radical prostatectomy.

TRENDS IN SURGICAL MANAGEMENT OF RENAL NEOPLASMS: SINGLE CENTER RESULTS IN THE LAST DECADE.

The majority of renal neoplasms can be treated surgically using open or minimally-invasive approach. Nephron-sparing surgery should be used when possible, regardless to the operative approach. In this retrospective study, we analyzed surgical trends of operative treatment of renal neoplasms in the period from February 2011 until December 2020. There were a total of 1031 procedures, 703 (68.2%) radical nephrectomies (RN) and 328 (31.8%) partial nephrectomies (PN). Laparoscopic approach was used in 211 (20.5%) (111 PN and 100 RN), while open approach was used in 820 (79.5%) (328 PN and 703 RN) cases. There were 12 procedures performed with the use of cardiopulmonary bypass and hypothermic arrest. The median operative time was 161 minutes for open RN and 158 for open PN, 160 for laparoscopic RN, and 162 for laparoscopic PN. The most common pathology was clear cell carcinoma in 693 (67.3%), papillary carcinoma in 115 (11.2%), chromophobe carcinoma in 67 (6.5%), oncocytoma in 46 (4.5%), and angiomyolipoma in 33 (3.2%) patients. Pathologically, pT1 stage was diagnosed in 56.9%, pT2 in 5.8%, pT3 in 22.4% and pT4 in 1.2% of patients. Regional lymphadenectomy was performed in 354 (34.3%) patients, among which lymph nodes were positive in 40 (11.3%) cases. Surgical margins were positive in 27 cases when PN was performed (8.2%). In conclusion, there was an ongoing raising trend in the number of procedures in general, and also in minimally invasive and nephron-sparing surgery in our study.

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.

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.

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.

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 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.

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.

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.

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.].