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.

Intravesical Gemcitabine and Docetaxel Therapy for BCG-Naïve Patients: A Promising Approach to Non-Muscle Invasive Bladder Cancer.

Bacillus Calmette-Guérin (BCG) therapy for patients with non-muscle invasive bladder cancer (NMIBC) faces limitations in efficacy and significant side effects, aggravated by a recent global shortage. In this prospective clinical study, we report the outcomes of sequential intravesical administration of gemcitabine and docetaxel (Gem/Doce) as a first-line treatment for BCG-naïve patients with high-risk NMIBC (HR NMIBC). From October 2019 until April 2022, we enrolled 52 patients and followed the treatment protocol set forth by the University of Iowa. Follow-up assessments were conducted every 3 months. In this cohort, 25 (48.1%) patients were diagnosed with high-grade T1 (T1HG) bladder cancer, 10 (19.2%) patients had carcinoma in situ (CIS), and 17 (32.7%) patients had a combination of T1HG+CIS. The median time to first recurrence in the T1HG, CIS, and T1HG+CIS groups was 11, 10.5, and 8.8 months, respectively. The recurrence-free survival was 98.1%, 94.2%, and 80.8% at 6, 9, and 12 months, respectively. The rate of progression-free survival was 100%, 98.1%, and 92.3% at 6, 9, and 12 months, respectively. We demonstrated the safety and efficacy of Gem/Doce therapy in BCG-naïve patients with HR NMIBC during a one-year follow-up. Further research with extended follow-ups, as well as direct comparisons of Gem/Doce with other anticancer agents, is essential.

ABO Blood Type and Urinary Bladder Cancer: Phenotype, Genotype, Allelic Association with a Clinical or Histological Stage and Recurrence Rate.

Background Previous research on connection between the ABO blood group and bladder cancer has been based on determining the ABO phenotype. This specific research is extended to the molecular level, providing more information about particular ABO alleles. Aim To investigate the impact of the ABO blood group genotype or phenotype as a risk factor for urinary bladder cancer. Materials and Methods In the case-control study, we included 74 patients who underwent surgery for a urinary bladder tumor at the Urology Clinic, Clinical Hospital Centre Zagreb, in 2021 and 2022. The control group comprised 142 asymptomatic and healthy blood donors. ABO genotyping to five basic alleles was done using a polymerase chain reaction with sequence-specific primers. We compared ABO phenotypes, genotypes, and alleles between patients and the healthy controls and investigated their distribution according to the clinical and histological stage and recurrence rate. Results No statistically significant difference was found among the groups, nor for the observed disease stages in terms of the phenotype and genotype. At the allele level, the results show a significantly lower proportion of malignancy in O1 ( p < 0.001), A1 ( p < 0.001), and B ( p = 0.013), and a lower proportion of metastatic disease in A2 (0%, p = 0.024). We also found significantly higher proportions of high-grade tumors in patients with O1 (71.4%, p < 0.001), A1 (70.1%, p = 0.019), of nonmuscle invasive tumors in patients with O1 (55.1%, p < 0.001), O2 (100%, p = 0.045), and recurrent tumors in patients with O1 (70.2%, p < 0.001) and A1 (74.2%, p = 0.007) alleles. Conclusion We did not find an association between the ABO blood group genotype or phenotype as a genetic risk factor for urinary bladder cancer. However, an analysis at the allelic level revealed a statistically significant association between certain alleles of the ABO blood group system and urinary bladder tumors, clinical or histological stage, and recurrence rate, respectively.

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.

Clinical utility of [68Ga]Ga-PSMA-11 PET/CT in initial staging of patients with prostate cancer and importance of intraprostatic SUVmax values.

BACKGROUND: As in disease recurrence, providing clinicians with the exact extent of the disease at the time of initial diagnosis is key in the management and individual treatment of prostate cancer (PC) patients. Intending to examine the usefulness of gallium- 68 PSMA-11 positron emission tomography/computed tomography ([68Ga]Ga-PSMA-11 PET/CT) and to determine if there is a correlation between prostate-specific antigen (PSA) serum values, WHO/ISUP (World Health Organization/International Society of Urological Pathology's) grade group of the tumor and SUVmax (maximized standardized uptake value) values we retrospectively analyzed PET/CT studies performed for initial staging of the disease. PATIENTS AND METHODS: We retrospectively evaluated 34 studies of patients who underwent [68Ga]Ga-PSMA-11 PET/CT as part of the initial staging of prostate cancer. All patients had prostate cancer confirmed by histological assessment after biopsy and had Gleason score and PSA serum values obtained. The mean PSA value was 33.8 ± 40.9 nmol/L (range 2.2-232). RESULTS: Nineteen patients had extended disease (55.9%). The mean SUVmax in prostate lesions was 19.5 ± 12.6. The mean value of SUVmax of PET studies in the high-risk group was significantly higher than those of low risk (23.5 ± 13.2 and 10.6 ± 5.4, p < 0.05). A positive correlation was observed between the ISUP group and SUVmax value of prostate lesions (Pearson's r = 0.557, p < 0.01). A positive correlation was also found in the comparison between PSA values and SUVmax (Pearson's r = 0.34, p < 0.05). CONCLUSIONS: In our study, [68Ga]Ga-PSMA-11 PET/CT scans detected the extended disease in more than half of the patients. Locating disease beyond the prostate gland allowed better informed clinical decisions and modified treatment. A positive correlation was found between intraprostatic SUVmax values and the ISUP group of prostate cancer. High-risk patients had SUVmax values that were significantly higher than those of low-risk patients. The correlation between the Gleason score and SUVmax value can be explained by the increased intensity of PSMA expression as the tumor grade increases.

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.

SACRAL NEUROMODULATION IN TREATING OVERACTIVE BLADDER PATIENTS - FIRST-TIME APPLICATION IN CROATIA.

Sacral neuromodulation (SNM) is a safe, efficacious, and minimally invasive advanced therapy that involves electrical stimulation to sacral nerve root to modulate neural pathway. Indications for SNM include symptoms of overactive bladder (OAB), urinary incontinence, urinary retention, urgency and frequency and, regarding bowel dysfunction, fecal incontinence . In Europe and Canada, indication is also established for chronic constipation. The mechanism of action is still not fully elucidated and complete understanding is yet to be determined. It is proposed that SNM modulates neural circuits in both central and peripheral pathways, thus having an impact on the brain, as well as on the bladder-targeting neuronal activity. Another possible significant effect on irregular bladder activity is through inhibition of the bladder afferent pathways by stimulation of the pudendal nerve. Over the past two decades, with more than 300 000 treated patients, SNM has confirmed its efficacy to relieve refractory OAB symptoms, as well as urinary retention or fecal incontinence. First SNM applications in Croatia were uneventful and we are glad to offer our patients this novel therapy in the future.

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.

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.

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.

MANAGEMENT OF PROSTATE CANCER IN KIDNEY TRANSPLANT RECIPIENTS.

Kidney transplantation is the treatment of choice in eligible patients with end-stage kidney disease. Prostate cancer (PC) is the second most common cancer in men worldwide. The prevalence of chronic kidney disease worldwide is 13.4%. The management of localized PC in these patients is challenging due to immunosuppressive therapy and pelvic graft localization. High graft and recipient survival rates have resulted in higher numbers of these patients in our everyday practice. A retrospective analysis of male patients who had undergone kidney transplantation at our center between 2002 and 2022 and were diagnosed and treated for PC was performed. We analyzed the incidence, treatment methods, and follow-up of PC patients in this population. A total of 1079 male patients were transplanted. PC was diagnosed in 12 patients (8 after and 4 before transplantation). The incidence of PC was 1.11%. Radical prostatectomy was performed in 11 patients, and one patient was treated with radical radiotherapy. Eleven patients had stable graft function; 1 graftectomy was performed, unrelated to PC. Three patients were indicated for salvage radiotherapy, one is in process for prostate-specific membrane antigen positron emission tomography (PSMA PET CT), and 7 patients are in follow-up and without recurrence. Radical prostatectomy is a safe treatment method for localized PC in kidney transplant recipients, which does not impair graft function and survival.

SHORT-TERM OUTCOMES OF PERCUTANEOUS RADIOFREQUENCY AND MICROWAVE ABLATION IN THE TREATMENT OF SMALL RENAL MASSES.

Although the gold standard in the management of kidney tumors is surgical treatment, thermal ablation methods are a viable therapeutic option for patients with small (<4 cm) renal masses who are poor surgical candidates. The aim of this study was to compare the technical success, primary efficacy and complication rate of percutaneous radiofrequency and microwave ablation in the treatment of small renal masses. A retrospective analysis of consecutive patients with small renal masses treated with radiofrequency or microwave ablation between December 2017 and January 2022 was conducted. Response to the ablative therapy was assessed on contrast-enhanced computed tomography examination after 3 months. Ablations of 44 kidney lesions were performed in 43 patients. Sixteen lesions were treated with radiofrequency and 28 with microwave ablation. Both methods were associated with high technical success (100%). Primary efficacy rates of radiofrequency and microwave ablation were 81.3% and 89.3%, respectively. Ablation-related complications were noted only in the patients treated with microwave ablation (18.5%), all of them being low grade (Clavien-Dindo 1 and 2). Radiofrequency and microwave ablation exhibited comparable efficacy in the treatment of small renal masses. Microwave ablation was associated with a comparatively higher number of complications.

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.

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.