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Background: Aldosterone synthase (CYP11B2) antibodies for immunohistochemistry, enables to visualize aldosterone-producing zona glomerulosa (ZG), aldosterone-producing micronodules, and aldosterone-producing adenomas. The architecture of the ZG differs in old versus young age but the evolution of the changes is not well known. The pathogenesis of aldosterone-producing micronodules and aldosterone-producing adenomas is still unclear and research on the ZG in young populations is limited. In this study, we elucidate changes in human ZG with age by quantifying the CYP11B2 expression., Methods: We collected 83 human adrenal glands from 57 autopsy cases aged 0 to 40 years old. In 26 cases, both adrenals were available. We performed immunohistochemistry targeting CYP11B2 and quantified the relative CYP11B2 expressing area, CYP11B2 continuity, the mean gap length between CYP11B2-expressing areas and the maximum extension of CYP11B2 area (depth)., Results: We found a negative correlation between age and the relative CYP11B2 expressing area, a negative correlation between age and CYP11B2 continuity, a positive correlation between age and mean gap length, and a positive correlation between age and maximum CYP11B2 depth. The changes in expression patterns of relative CYP11B2 expressing area, CYP11B2 continuity and mean gap length were seen in both adrenals of the same autopsy case., Conclusions: The decline of relative CYP11B2 expressing ZG area and continuity may indicate involution of the ZG, which is supported by an increase of gaps and maximum CYP11B2 depth indicating clustering, comparable to formation of aldosterone-producing micronodules. The similarities in both adrenals from the same case indicate that these changes occur bilaterally.

Introduction: Primary aldosteronism (PA) is the most common form of secondary hypertension. It is caused by overproduction of aldosterone by either a unilateral aldosterone-producing adenoma (APA) or by bilateral adrenal hyperplasia (BAH). Distinction is crucial, because PA is cured by adrenalectomy in APA and is treated by mineralocorticoid receptor antagonists in BAH. The distinction is currently made by adrenal vein sampling (AVS). AVS is a costly, invasive and complex technical procedure with limited availability and is not superior in terms of outcomes to CT scan-based diagnosis. Thus, there is a need for a cheaper, non-invasive and readily available diagnostic tool in PA. We propose a new diagnostic imaging modality employing the positron emission tomography (PET) tracer [ 68 Ga]Ga-PentixaFor. This tracer has high focal uptake in APAs, whereas low uptake was shown in patients with normal adrenals. Thus, [ 68 Ga]Ga-PentixaFor PET/CT is an imaging modality with the potential to improve subtyping of PA. It is readily available, safe and, as an out-patient procedure, much cheaper diagnostic method than AVS., Methods and Analysis: We present a two-step randomised controlled trial (RCT) protocol in which we assess the accuracy of [ 68 Ga]Ga-PentixaFor PET/CT in the first step and compare [ 68 Ga]Ga-PentixaFor PET/CT to AVS in the second step. In the first step, the concordance will be determined between [ 68 Ga]Ga-PentixaFor PET/CT and AVS and a concordance probability is calculated with a Bayesian prediction model. In the second step, we will compare [ 68 Ga]Ga-PentixaFor PET/CT and AVS for clinical outcome and intensity of hypertensive drug use defined as daily defined doses in a RCT., Ethics and Dissemination: Ethics approval was acquired from the medical ethical committee East-Netherlands (METC Oost-Nederland). Results will be disseminated through peer-reviewed articles., Trial Registration Number: NL9625., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Over the years, five different Trifecta score definitions have been proposed to optimize the framing of "success" in partial nephrectomy (PN) field. However, such classifications rely on different metrics. The aim of the present study was to explore how the success rate of robotic PN, as well as its drivers, vary according to the currently available definitions of Trifecta., Methods: Data from consecutive patients with cT1-2N0M0 renal masses treated with robotic PN at 16 referral centers from September 2014 to March 2015 were prospectively collected. Trifecta rate was defined for each of the currently available definitions. Multivariable logistic regression analysis was used to evaluate possible predictors of "Trifecta failure" according to the different adopted formulation., Results: Overall, 289 patients met the inclusion criteria. Among the definitions, Trifecta rates ranged between 66.4% and 85.9%. Multivariable analysis showed that predictors for "Trifecta failure" were mainly tumor-related (i.e. tumor's nephrometry) for those Trifecta scores relying on WIT as a surrogate metric for postoperative renal function deterioration (definitions 1,2), while mainly surgery-related (i.e. ischemia time and excision strategy) for those including the percentage change in postoperative eGFR as the functional cornerstone of Trifecta (definitions 3-5)., Conclusions: There was large variability in rates and predictors of "unsuccessful PN" when using different Trifecta scores. Further research is needed to improve the value of the Trifecta metrics, integrating them into routine patient counseling and standardized assessment of surgical quality across institutions.

Background: To explore predictors of positive surgical margins (PSM) after robotic partial nephrectomy (PN) in a large multicenter international observational project, harnessing the Surface-Intermediate-Base (SIB) margin score to report the resection technique after PN in a standardized way. Methods: Data from consecutive patients with cT1-2N0M0 renal masses treated with PN from September 2014 to March 2015 at 16 tertiary referral centers and included in the SIB margin score International Consortium were prospectively collected. For the present study, only patients treated with robotic PN were included. Uni- and multivariable analysis were fitted to explore clinical and surgical predictors of PSMs after PN. Results: Overall, 289 patients were enrolled. Median (IQR) preoperative tumor size was 3.0 (2.3−4.2) cm and median (IQR) PADUA score was 8 (7−9). SIB scores of 0−2 (enucleation), 3−4 (enucleoresection) and 5 (resection) were reported in 53.3%, 27.3% and 19.4% of cases, respectively. A PSM was recorded in 18 (6.2%) patients. PSM rate was 4.5%, 11.4% and 3.6% in case of enucleation, enucleoresection and resection, respectively. Patients with PSMs had tumors with a higher rate of contact with the urinary collecting system (55.6% vs. 27.3%; p < 0.001) and a longer median warm ischemia time (22 vs. 16 min; p = 0.02) compared with patients with negative surgical margins, while no differences emerged between the two groups in terms of other tumor features (i.e., pathological diameter, PADUA score). In multivariable analysis, only enucleoresection (SIB score 3−4) versus enucleation (SIB score 0−2) was found to be an independent predictor of PSM at final pathology (HR: 2.68; 95% CI: 1.25−7.63; p = 0.04), while resection (SIB score 5) was not. Conclusions: In our experience, enucleoresection led to a higher risk of PSMs as compared to enucleation. Further studies are needed to assess the differential impacts of resection technique and surgeon’s experience on margin status after robotic PN.

Introduction: We aimed to compare the outcomes of open vs robotic partial nephrectomy (PN), focusing on predictors of Trifecta failure in patients with highly complex renal masses., Patients and Methods: We queried the prospectively collected database from the SIB International Consortium, including 507 consecutive patients with cT1-2N0M0 renal masses treated at 16 high-volume referral centres, to select those with highly complex (PADUA score ≥10) tumors undergoing PN. RT was classified as enucleation, enucleoresection or resection according to the SIB score. Trifecta was defined as achievement of negative surgical margins, no acute kidney injury and no Clavien-Dindo grade ≥2 postoperative surgical complications. Multivariable logistic regression analysis was used to assess independent predictors of Trifecta failure., Results: 113 patients were included. Patients undergoing open PN (n = 47, 41.6%) and robotic PN (n = 66, 58.4%) were comparable in baseline characteristics. RT was classified as enucleation, enucleoresection and resection in 46.9%, 34.0% and 19.1% of open PN, and in 50.0%, 40.9% and 9.1% of robotic PN (p = 0.28). Trifecta was achieved in significantly more patients after robotic PN (69.7% vs. 42.6%, p = 0.004). On multivariable analysis, surgical approach (open vs robotic, OR: 2.62; 95%CI: 1.11-6.15, p = 0.027) and tumor complexity (OR for each additional unit of the PADUA score: 2.27; 95%CI: 1.27-4.06, p = 0.006) were significant predictors of Trifecta failure, while RT was not. The study is limited by lack of randomization; as such, selection bias and confounding cannot be entirely ruled out., Conclusions: Tumor complexity and surgical approach were independent predictors of Trifecta failure after PN for highly complex renal masses., Competing Interests: Declaration of competing interest All authors disclose any financial and personal relationships with other people or organizations that could inappropriately influence their work., (Copyright © 2021 Elsevier Ltd, BASO ~ The Association for Cancer Surgery, and the European Society of Surgical Oncology. All rights reserved.)

Introduction: The use of fluoroscopy during percutaneous nephrolithotomy (PCNL) may lead to an overestimation of stone-free rates. The objective of this study is to demonstrate the feasibility of intraoperative CT-guided PCNL compared with standard of care (SoC) PCNL. Patients and Methods: A prospective feasibility study (20 patients undergoing PCNL with an intraoperative CT scan between June 2017 and February 2020) and a retrospective study of a historical cohort (20 consecutive patients undergoing SoC PCNL between September 2015 and September 2016) were conducted. All procedures were performed by an expert endourologist in a tertiary referral hospital. Follow-up was performed at 6 weeks postoperatively. The primary goal is to investigate the practicality and potential benefits and harms of intraoperative CT scanning during PCNL. Secondary outcomes are a stone-free rate after the 6-week follow-up, perioperative radiation exposure, the need for postoperative imaging, and peri- and postoperative complications. Statistical significance was considered at p  < 0.05. Results: The initial stone-free rate in the CT scan group was 65% ( n  = 13). In 25% ( n  = 5) of patients, residual stone fragments were removed after the perioperative CT scan. In the SoC group, 85% ( n  = 17) of patients were thought to be stone free perioperatively. At the 6-week follow-up, 80% ( n  = 16) in the CT scan group vs 50% in the SoC group ( n  = 10) were found to be stone free. Radiation exposure, perioperatively, was higher in the CT scan group. Complications were comparable between groups. Limitations of the study are the nonrandomized design of the study and nonstandardized follow-up imaging. Conclusions: Intraoperative CT scanning during PCNL is feasible and gives a better estimate of any remaining stone fragments compared with fluoroscopy only.

Background: Different techniques for laparoscopic adrenalectomy have been proposed with the lateral transperitoneal approach and posterior retroperitoneal approach being the two more frequently minimally invasive surgeries in most of the clinics. There are no sufficient studies in which the results of lateral transperitoneal and posterior retroperitoneal approaches in synchronous bilateral laparoscopic adrenalectomy have been compared. In the current study, we aimed to report our multicenter results of the lateral transperitoneal and posterior retroperitoneal synchronous bilateral laparoscopic adrenalectomy experience in patients who had different bilateral adrenal pathologies and to compare the outcomes of these two different operative procedures., Methods: Between 2012 and 2018, a total of 52 patients with a mean age of 43.5 years underwent simultaneous bilateral laparoscopic adrenalectomy at 6 different centers. Twenty-seven and 25 patients underwent bilateral lateral transperitoneal and posterior retroperitoneal laparoscopic adrenalectomy, respectively. Patients' age, gender, body max index, operative indications, mass size, operation time, blood loss, length of hospitalization, intraoperative and postoperative complications and pathology reports were analyzed., Results: Synchronous bilateral transperitoneal group was younger than synchronous posterior retroperitoneal group (37 years vs. 50.4 years.) (p: 0.001). Posterior retroperitoneal group had significantly decreased operating time and less blood loss than transperitoneal group. No significant difference was found with regard to postoperative hospital stay, perioperative and postoperative complications between two groups. Majority of the histopathological results were adrenal hyperplasia associated with Cushing's disease (61.5%). Less frequent pathological results were adrenal adenoma and pheochromocytoma (15.4% and 13.5%, respectively). During the follow-up period, no recurrence or disease-related mortality was observed in the patients., Conclusion: Our results shows that shorter operative time and less bleeding can be achieved with posterior retroperitoneal approach in synchronous bilateral laparoscopic adrenalectomy. In our series, intraoperative and postoperative complication rates were similar between both surgical approaches.

Purpose: The impact of resection technique on partial nephrectomy outcomes is controversial. The aim of this study was to evaluate the pattern of resection techniques during partial nephrectomy and the impact on perioperative outcomes, acute kidney injury, positive surgical margins and the achievement of the Trifecta (negative surgical margins, no perioperative Clavien-Dindo grade 2 or greater surgical complications and no postoperative acute kidney injury)., Materials and Methods: We prospectively collected data on consecutive patients with cT1-2N0M0 renal masses treated with partial nephrectomy at a total of 16 referral centers from September 2014 to March 2015. After partial nephrectomy the resection technique was classified by the surgeon as enucleation, enucleoresection or resection according to the SIB (Surface-Intermediate-Base) margin scores 0 to 2, 3 or 4 and 5, respectively. Multivariable logistic regression analysis was done to evaluate the potential impact of the resection technique on postoperative surgical complications, positive surgical margins, acute kidney injury and Trifecta achievement., Results: Overall 507 patients were included in analysis. The resection technique was classified as enucleation in 266 patients (52%), enucleoresection in 150 (30%) and resection in 91 (18%). The resection technique (enucleoresection vs enucleation and resection) was the only significant predictor of positive surgical margins. Tumor complexity, surgical approach (open and laparoscopic vs robotic) and resection technique (enucleoresection vs enucleation) were significant predictors of Clavien-Dindo grade 2 or greater surgical complications. The surgical approach (open and laparoscopic vs robotic), the resection technique (enucleoresection vs enucleation) and warm ischemia time were significantly associated with postoperative acute kidney injury and Trifecta achievement., Conclusions: Resection techniques significantly impact surgical complications, early functional outcomes and positive surgical margins after partial nephrectomy of localized renal masses.

Purpose: Partial nephrectomy (PN) is standard for small renal masses, improving renal function by preserving renal parenchyma compared with radical nephrectomy. Recent work demonstrated that postoperative surgeon assessment of volume preservation (SAVP) and 3D imaging measurements agree and correlate with postoperative function. We hypothesize preoperative assessment of volume preservation (PAVP) with PN based on preoperative imaging will reliably indicate postoperative renal function., Materials and Methods: Data were collected from 336 patients undergoing PN for suspected renal cancer by 40 surgeons at 12 centers in Europe and the United States within the Surface-Intermediate-Base International Consortium. Surgeons recorded PAVP and SAVP for individual patients; pre- and postoperative glomerular filtration rate (GFR) was estimated by Chronic Kidney Disease Epidemiology Collaboration equations. Correlations between PAVP, SAVP, and postoperative GFR were assessed with linear regression models. Bland-Altman analysis was used to assess agreement between PAVP and SAVP with a significant cutoff of 5%., Results: Median PAVP was 90% (interquartile range [IQR] 85%-100%) and SAVP was 90% (IQR: 80%-94%). PAVP and SAVP were moderately correlated (R 2  = 0.67, P < 0.0001) and deemed "interchangeable" by Bland-Altman analysis at a 5% acceptable rate of difference (95% CI: -5.4, -3.1). Median postoperative GFR was 77.3 (IQR: 56.2, 92.0). Both PAVP (R 2  = 0.82, P < 0.0001) and SAVP (R 2  = 0.83, P < 0.0001) were correlated with postoperative GFR. Multivariable models utilizing volume-adjusted GFR based on PAVP or SAVP significantly and similarly predicted postoperative GFR (R 2  = 0.72 for each)., Conclusion: Renal function is closely linked to the amount of parenchymal volume preservation, whether estimated prior to surgery (PAVP) or afterward (SAVP). PAVP provides reasonably accurate information for decision-making in patients considering PN., (Copyright © 2018. Published by Elsevier Inc.)

Context: In primary aldosteronism (PA), two subtypes are distinguished: aldosterone-producing adenoma (APA) and bilateral adrenal hyperplasia (BAH). In general, these are treated by adrenalectomy (ADX) and mineralocorticoid receptor antagonists (MRA), respectively., Objective: To compare the effects of surgical treatment and medical treatment on quality of life (QoL)., Design: Post hoc comparative effectiveness study within the Subtyping Primary Aldosteronism: A Randomized Trial Comparing Adrenal Vein Sampling and Computed Tomography Scan (SPARTACUS) trial., Setting: Twelve Dutch hospitals and one Polish hospital., Participants: Patients with PA (n = 184)., Interventions: ADX or MRAs., Main Outcome Measures: At baseline and 6-month and 1-year follow-up, we assessed QoL by two validated questionnaires: RAND 36-Item Health Survey 1.0 (RAND SF-36) and European Quality of Life-5 Dimensions (EQ-5D)., Results: At baseline, seven of eight RAND SF-36 subscales and both summary scores, as well as three of five EQ-5D dimensions and the visual analog scale, were lower in patients with PA compared with the general population, especially in women. The beneficial effects of ADX were larger than for MRAs for seven RAND SF-36 subscales, both summary scores, and health change. For the EQ-5D, we detected a difference in favor of ADX in two dimensions and the visual analog scale. Most differences in QoL between both treatments exceeded the minimally clinically important difference. After 1 year, almost all QoL measures had normalized for adrenalectomized patients. For patients on medical treatment, most QoL measures had improved but not all to the level of the general population., Conclusion: Both treatments improve QoL in PA, underscoring the importance of identifying these patients. QoL improved more after ADX for suspected APA than after initiation of medical treatment for suspected BAH., (Copyright © 2017 Endocrine Society)

Background: Laparoscopic surgery may be complicated by visual disturbances, including lens fogging. Several techniques have been developed to prevent laparoscopic lens fogging (LLF). We aim to compare the effectiveness of two commonly available techniques in prevention of LLF: heated sterile water in a thermos flask and ResoClear ® impregnation wipes., Materials and Methods: In this single-center prospective randomized study, 50 patients underwent an elective laparoscopic donor nephrectomy and were allocated to either heated sterile water or ResoClear ® impregnation wipes as the antifogging method. The primary outcome was the number of fogging events during the first 30 minutes of the operation, whereas secondary outcomes were operating time, number of cleaning events because of other causes, cost differences, and assessment of predicting factors for fogging events., Results: In 50 patients, the outcomes were analyzed. The number of fogging events was significantly lower when using heated sterile water (median = 0, interquartile range [IQR]: 0-0) compared to ResoClear ® (median 1.0, IQR: 0.5-3.0), p < 0.001. There were no significant differences in operating time, number of cleaning events because of other causes, and costs. No predictors of fogging events were found., Conclusion: The use of heated sterile water leads to significantly less fogging events than the use of ResoClear ® impregnation wipes, resulting in an improved continuity of the surgery without differences in operating time and costs.

Context: Controversy exists regarding the choice for surgical approach and the role of lymph node dissection (LND) in adrenocortical carcinoma (ACC) treatment. ACC surgery is increasingly advocated to be performed in specialist referral centres., Objective: To review systematically the evidence of oncologic outcomes for ACC surgery by open adrenalectomy (OA) or laparoscopic adrenalectomy (LA), and for concomitant LND. The influence of surgical volume is also analysed., Evidence Acquisition: A systematic review of Ovid Medline, Embase, and the Cochrane Library was performed in June 2015 according to the Preferred Reporting Items for Systematic Review and Meta-analysis statement. Twenty-six publications were selected for inclusion in the analysis. Meta-analyses were performed when appropriate., Evidence Synthesis: Included studies reported on oncologic outcomes after surgical treatment of ACC (11 studies), compared different surgical approaches (7 studies), evaluated the role of LND (3 studies), and analysed the effect of surgical volume on outcome (5 studies). From the available studies and the meta-analysis, no differences were found in the rate of positive surgical margins, disease-free survival, and overall survival between OA and LA in localised disease. In patients with histologically proven positive lymph nodes, a shorter time to recurrence was seen when no proper LND was performed. A trend for better recurrence-free survival and disease-specific survival after LND was found. In high-volume centres, more aggressive and open surgery was performed. In low-volume centres, higher local recurrence and distant metastases rates, and a shorter time to recurrence were seen. Our findings are limited due to the low level of evidence of selected studies, patient and disease heterogeneity, and heterogeneous surgeon populations., Conclusions: After adequate clinical staging for localised disease, LA is as effective and oncologically safe as OA, as long as oncologic principles are respected. LA should be performed by surgeons with extensive experience in laparoscopic adrenal surgery in high-volume centres. Patients with locally advanced disease and metastatic disease, for debulking purposes, should be operated on extensively with open surgery with adequate margins and concomitant LND to optimise staging, which may contribute to survival in locally advanced disease., Patient Summary: Laparoscopic surgery for localised adrenocortical carcinoma is safe and effective when performed by expert surgeons in high-volume centres. Patients with more extensive tumours should be operated with open surgery; lymph node dissection is mainly applied to determine the stage of the disease., (Copyright © 2015 European Association of Urology. Published by Elsevier B.V. All rights reserved.)