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.

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.

Histopathological Features of Time-Zero Kidney Biopsy Are Predictive Factors for Posttransplant Anemia.

INTRODUCTION: Posttransplant anemia (PTA) is a common complication of kidney transplantation, associated with reduced graft survival and higher mortality. We aimed to determine the association of PTA with histopathological characteristics of time-zero allograft biopsy and donor clinical characteristics. METHODS: We conducted a retrospective, observational cohort study that included 587 patients who underwent kidney transplantation in our center. Hemoglobin levels were assessed at 6 and 12 months after transplantation, and anemia was defined according to World Health Organization criteria. The kidney allograft time-zero biopsy has been done in all investigated cases. The evaluated histopathological parameters of the kidney allografts included glomerulosclerosis, arteriolar hyalinosis (AH), vascular fibrous intimal thickening (CV), interstitial fibrosis, tubular atrophy, and interstitial fibrosis and tubular atrophy. The Banff Classification of Allograft Pathology criteria were followed to assess the allograft histopathological changes. RESULTS: The prevalence of anemia was 31.3% at 6 months after transplantation and 23.5% at 12 months. There was an association between 20-50% glomerulosclerosis and PTA in both time points, independently from estimated glomerular filtration rate. AH and interstitial fibrosis were identified as independent risk factors for anemia 6 months after transplantation. CONCLUSION: Histopathological features of time-zero kidney biopsy may be predictors of PTA. Among them, our study recognized 20-50% degree of glomerulosclerosis, AH, and CV as the most significant risk factors for PTA.

Collapsing Focal Segmental Glomerulosclerosis After Kidney Transplantation: Is It a Consequence of Viral Infections?

BACKGROUND: The aim of this case study was to explore the possible link between viral infections and collapsing focal segmental glomerulosclerosis (cFSGS) in patients who underwent kidney transplantation. METHODS: This case study included 3 case reports of patients who underwent kidney transplantation. The case reports were presented clinically and pathohistologically with cFsGS as a possible consequence of viral infections. RESULTS: The first patient developed cFSGS after polymerase chain reaction for SARS-CoV2 was positive twice. He gradually developed terminal stage chronic kidney disease. The second patient developed cFSGS with high range proteinuria after cytomegalovirus infection, which has been treated with 3 lines of antiviral medicaments. The third patient developed cFSGS as a possible consequence of hepatitis B virus infection. CONCLUSIONS: This case study highlighted the importance of viral etiology in the pathway of cFSGS. Pathogenic links between viral infections and concomitant glomerulopathies are challenging, especially in immunocompromised transplanted patients.

Comprehensive Clinical and Genetic Analysis of CHEK2 in Croatian Men with Prostate Cancer.

Germline pathogenic and likely pathogenic (P/LP) variants in CHEK2 have been associated with increased prostate cancer (PrCa) risk. Our objective was to analyze their occurrence in Croatian PrCa men and to evaluate the clinical characteristics of P/LP variant carriers. Therefore, we analyzed CHEK2 in 150 PrCa patients unselected for age of onset, family history of PrCa or clinical outcome, and the frequency of identified variants was compared to findings in 442 cancer-free men, of Croatian ancestry. We identified four PrCa cases harboring a P/LP variant in CHEK2 (4/150, 2.67%), which reached a statistical significance (p = 0.004) as compared to the control group. Patients with P/LP variants in CHEK2 developed PrCa almost 9 years earlier than individuals with CHEK2 wild-type alleles (8.9 years; p = 0.0198) and had an increased risk for lymph node involvement (p = 0.0047). No association was found between CHEK2 status and further clinical characteristics, including the Gleason score, occurrence of aggressive PrCa, the tumor or metastasis stage. However, carriers of the most common P/LP CHEK2 variant, the c.1100delC, p.Thr367Metfs15*, had a significantly higher Gleason score (p = 0.034), risk for lymph node involvement (p = 0.0001), and risk for developing aggressive PrCa (p = 0.027). Thus, in a Croatian population, CHEK2 P/LP variant carriers were associated with increased risk for early onset prostate cancer, and carriers of the c.1100delC, p.Thr367Metfs15* had increased risk for aggressive PrCa.

Urethral pressure profile before radical prostatectomy as a predictor of early postoperative continence.

OBJECTIVE: Urinary incontinence (UI) is one of the most common complications of radical prostatectomy (RP). Impaired urethral sphincter function is generally considered to be the most important contributing factor for UI; however, the mechanism of onset and recovery of urinary continence has not been fully elucidated. The objective of this research was to evaluate preoperative functional urethral length (FUL) and maximum urethral closure pressure (MUCP) as early continence recovery predictors after open retropubic RP (ORRP). METHODS: The research was conducted on a group of 43 patients with localized prostate cancer (PCa) in the period from July 2019 to May 2021. The urodynamic method of urethral pressure profile (UPP) was used to assess FUL and MUCP, and correlate with the postprostatectomy continence recovery. The severity of UI and bothersome were assessed using fully validated International Consultation on Incontinence Questionnaire - Urinary Incontinence Short Form (ICIQ-UI SF) and number of pads used in 24 h. Patients were interviewed about the use of urinary pads and asked to fill out the ICIQ-UI SF before and 2, 8, 16 and 24 weeks after ORRP. RESULTS: The median value of FUL (mm) and MUCP (cmH2O) was 69 (28-94) and 76 (16-223), respectively. Correlation and linear regression showed a statistically significant negative correlation between preoperative values of FUL and MUCP with ICIQ symptom score and the number of pads used per day at the four observed time intervals (p < 0.05). Such a result showed that patients with higher preoperative FUL and MUCP values were more likely to recover urinary continence earlier. A value of 65 mm for FUL and 80 cmH2 O for MUCP proved to be the cut-off values for continence recovery in 24 weeks after ORRP. CONCLUSION: Preoperatively evaluated FUL and MUCP seem to be valuable prognostic factors for early continence recovery after ORRP. Further investigation on a larger patient cohort is needed to evaluate the role of UPP in the preoperative management of patients with PCa.

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.].

ANESTHESIA FOR ROBOT-ASSISTED RADICAL PROSTATECTOMY - A CHALLENGE FOR ANAESTHESIOLOGIST.

Mininimally invasive surgery has become one of the most popular ones over the last few decades due to many benefits. The advantages are minimal surgical incision, reduced blood loss, reduced postoperative pain, faster postoperative recovery, shorter hospital stay, lower morbidity and better outcomes compared to open surgery. The most common robotic procedures in urology are radical prostatectomies. In UHC Zagreb, since November 2019 until now, there have been more than 180 robotic assisted radical prostatectomies (RALP) using Senhance robotic system performed. As a procedure with many possible complications, it represents a challenge for anaesthesiologist. Some of the problems the anaesthesiologists have to face are related to limited patient access, possible difficulties connected with positioning, pneumoperitoneum, subcutaneous emphysema, possible airway oedema. Pneumoperitoneum has impact on almost every system: cardiovascular, renal, respiratory, gastrointestinal and other. Detailed understanding of physiological changes of RALP, with intraoperative impact on nearly every body system is ultimate. Careful preoperative evaluation and intraoperative conduction minimize the risk of complications, and help patients to reach full recovery in a very short time. Excellent outcomes are the result of individualized approach to the patient and good communication between team members.

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.

Hospitalization and death after recovery from acute COVID-19 among renal transplant recipients.

INTRODUCTION: Data on post-COVID-19 in renal transplant recipients (RTR) is scarce. We investigated the rate of hospitalizations, reasons for hospital admission, and mortality rate among RTR who survived acute COVID-19. METHODS: A multi-center retrospective observational cohort study measured hospital admission and death to 180 days after acute SARS-CoV-2 infection in 308 adult patients. RESULTS: The median age was 57 years, 64.9% were male. All patients had at least one comorbidity, and 26.3% had diabetes. Data on post-COVID-19 course was available for 267 patients, and 49 of them (15.9%) required hospital treatment after recovery from the acute infection. The most common indications included pneumonia (24.5%) and renal allograft dysfunction (22.4%), 7 (14.3%) had sepsis and 5 (10.2%) had thrombotic events. A median duration of the hospital stay was 12 days. Six patients (2.2%) died due to multiorgan failure, respiratory insufficiency or urosepsis. The strongest predictor for hospitalization after acute COVID-19 was hospitalization for acute SARS-CoV-2 infection, while better allograft function decreased the probability of hospitalization. CONCLUSION: Delayed consequences of acute COVID-19 are highly prevalent and the health care systems should be prepared to respond to the needs of RTR suffering from post-COVID-19 complications.

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.

SCROTAL THERMOGRAPHY IN THE EVALUATION OF SURGICAL OUTCOME AFTER VARICOCELE REPAIR: A CASE REPORT.

Scrotal thermography is a diagnostic method for varicocele. In short, there are five diagnostic thermographic criteria for varicocele, i.e., pattern of scrotal thermographic image indicative of varicocele, temperature at pampiniform plexus ≥34 C°, temperature difference between left and right pampiniform plexus ≥0.5 C°, enhancement of image during Valsalva maneuver, and temperature at pampiniform plexus ≥ temperature at ipsilateral thigh. Three or more positive signs are indicative of varicocele. The aim of this report is to present the use of digital thermography as a diagnostic method to evaluate the outcome of varicocele repair. We present a case of a student diagnosed with varicocele grade III, and assessed preoperatively and followed up postoperatively by scrotal thermography. According to thermographic indicators, our patient was positive for varicocele diagnosis before surgical treatment. Three months after varicocele repair, the patient did not show positive thermographic indicators of varicocele while physical examination and color Doppler ultrasound were equivocal. This case report suggests that infrared digital thermography of scrotum could be very valuable for monitoring patients in the period after surgery for varicocele, however, it should be confirmed in a larger number of patients.

cfDNA methylation in liquid biopsies as potential testicular seminoma biomarker.

Background: Seminoma is a testicular tumor type, routinely diagnosed after orchidectomy. As cfDNA represents a source of minimally invasive seminoma patient management, this study aimed to investigate whether cfDNA methylation of six genes from liquid biopsies, have potential as novel seminoma biomarkers. Materials & methods: cfDNA methylation from liquid biopsies was assessed by pyrosequencing and compared with healthy volunteers' samples. Results: Detailed analysis revealed specific CpGs as possible seminoma biomarkers, but receiver operating characteristic curve analysis showed modest diagnostic performance. In an analysis of panels of statistically significant CpGs, two DNA methylation panels emerged as potential seminoma screening panels, one in blood CpG8/CpG9/CpG10 (KITLG) and the other in seminal plasma CpG1(MAGEC2)/CpG1(OCT3/4). Conclusion: The presented data promote the development of liquid biopsy epigenetic biomarkers in the screening of seminoma patients.

Seminoma belongs to testicular cancer, which represents a common malignancy among men of reproductive age. Diagnosis of seminoma is a multistep process that also includes checking tumor biomarkers from blood. However, these biomarkers are not specific for seminoma and to conclude a definite diagnosis of seminoma immunohistochemical analysis is needed, which requires the removal of a whole or partial testicle. Therefore, there is a need for novel, noninvasive biomarkers. cfDNA is the most extensively investigated source of minimally invasive tumor markers. Therefore, this study investigated cfDNA methylation of six genes as potential noninvasive biomarkers for the management of seminoma patients. By examining CpG sites of selected genes by pyrosequencing, the authors detected significant differences. However, receiver operating characteristic curve analysis showed modest results. Therefore, the authors tested possible panels of significantly different CpGs and detected two possible DNA methylation panels for seminoma screening. These findings suggest the further investigation of possible epigenetic biomarkers for seminoma patient management from liquid biopsies.