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Objective Few and conflicting reports have characterized the genetics of paediatric pheochromocytomas and paragangliomas (PPGLs). This study aimed to investigate the clinical and genetic features of Brazilian children with PPGL. Patients and methods This study included 25 children (52% girls) with PPGL. The median age at diagnosis was 15 years (4-19). The median time of follow-up was 145 months. The genetic investigation was performed by Sanger DNA sequencing, multiplex ligation-dependent probe amplification and/or target next-generation sequencing panel. Results Of the 25 children with PPGL, 11 (44%), 4 (16%), 2 (8%), 1 (4%) and 7 (28%) had germline VHL pathogenic variants, SDHB, SDHD, RET and negative genetic investigation, respectively. Children with germline VHL missense pathogenic variants were younger than those with SDHB or SDHD genetic defects [median (range), 12 (4-16) vs. 15.5 (14-19) years; P = .027]. Moreover, 10 of 11 cases with VHL pathogenic variants had bilateral pheochromocytoma (six asynchronous and four synchronous). All children with germline SDHB pathogenic variants presented with abdominal paraganglioma (one of them malignant). The two cases with SDHD pathogenic variants presented with head and neck paraganglioma. Among the cases without a genetic diagnosis, 6 and 2 had pheochromocytoma and paraganglioma, respectively. Furthermore, metastatic PPGL was diagnosed in four (16%) of 25 PPGL. Conclusions Most of the paediatric PPGL were hereditary and multifocal. The majority of the affected genes belong to pseudohypoxic cluster 1, with VHL being the most frequently mutated. Therefore, our findings impact surgical management and surveillance of children with PPGL.

Familial primary aldosteronism (PA) is rare and mostly diagnosed in early-onset hypertension (HT). However, ‘sporadic’ bilateral adrenal hyperplasia (BAH) is the most frequent cause of PA and remains without genetic etiology in most cases. Our aim was to investigate new genetic defects associated with BAH and PA. We performed whole-exome sequencing (paired blood and adrenal tissue) in six patients with PA caused by BAH that underwent unilateral adrenalectomy. Additionally, we conducted functional studies in adrenal hyperplastic tissue and transfected cells to confirm the pathogenicity of the identified genetic variants. Rare germline variants in phosphodiesterase 2A (PDE2A) and 3B (PDE3B) genes were identified in three patients. The PDE2A heterozygous variant (p.Ile629Val) was identified in a patient with BAH and early-onset HT at 13 years of age. Two PDE3B heterozygous variants (p.Arg217Gln and p.Gly392Val) were identified in patients with BAH and HT diagnosed at 18 and 33 years of age, respectively. A strong PDE2A staining was found in all cases of BAH in zona glomerulosa and/or micronodules (that were also positive for CYP11B2). PKA activity in frozen tissue was significantly higher in BAH from patients harboring PDE2A and PDE3B variants. PDE2A and PDE3B variants significantly reduced protein expression in mutant transfected cells compared to WT. Interestingly, PDE2A and PDE3B variants increased SGK1 and SCNN1G/ENaCg at mRNA or protein levels. In conclusion, PDE2A and PDE3B variants were associated with PA caused by BAH. These novel genetic findings expand the spectrum of genetic etiologies of PA.

To evaluate in an experimental model, the mobility of a novel peritoneal dialysis catheter with a metallic tip (Mag-Cath) using an extra-corporeal magnet. The Mag-Cath was installed in a porcine model under general anesthesia using laparoscopic access. A senior urologist, a urology resident, and a 3rd-year medical student were assigned to complete 2 tasks guided by fluoroscopy: (1) Move the catheter tip from the right flank to the pelvis and (2) move the catheter tip from the pelvis to the left flank. Accomplishment and time to complete the tasks were recorded. Participants were asked independently to grade the difficulty of the tasks using an analog scale from 1 (extremely easy) to 10 (extremely difficult). All participants completed the tasks. The difficulty of the tasks was graded equal to 1 by the senior urologist and urology resident and equal to 3 by the medical student. The time to move the Mag-Cath from the right flank to the target was 14, 10, and 55 s for the senior urologist, urology resident, and medical student, respectively. The time to move the Mag-Cath from the target to the left flank was 17, 18, and 43 s for the senior urologist, urology resident, and medical student, respectively. In this preliminary analysis, the use of an extra-corporeal magnet to move the Mag-Cath was feasible, with a low grade of difficulty, and individuals with different levels of expertise could perform it. Further studies in human subjects are needed to evaluate the clinical applicability of the Mag-Cath properly.

To evaluate outcomes of laparoscopic pyeloplasty (LP) in adults with poorly functioning kidney due to ureteropelvic junction obstruction (UPJO). A retrospective comparative analysis was performed between adult patients who underwent LP due to UPJO with differential renal function (DRF) ≤ 15% and DRF > 15%. LP success rate and complications were assessed. LP success was defined as symptoms improvement and DRF improvement or stabilization. DRF and estimated glomerular filtration rate (eGFR) were analyzed before and 12 months after surgery to evaluate renal function recovery. DRF was estimated using Tc-99 m DMSA renal scintigraphy. Among 121 LP performed in the study period at our institution, 15 and 42 were included in the DRF ≤ 15% and DRF > 15% groups, respectively. At a median follow-up of 17.8 months, all patients with DRF ≤ 15% reported symptoms improvement. LP success rate was 86.7% and 90.5% (p = 0.65) for patients with DRF ≤ 15% and DRF > 15%, respectively. There were no complications in the DRF ≤ 15% group, while there were three complications recorded in the DRF > 15% group (Clavien 2 and 3b). In the DRF ≤ 15% group, mean pre-operative and post-operative DRF was 9.5% ± 3.6 and 10.5% ± 7.8 (p = 0.49), respectively. Median pre-operative and post-operative eGFR was 68.5 ml/min and 79.8 ml/min (p = 0.93), respectively. Two patients had DRF improvement after LP. LP in adult patients with UPJO and poor function kidneys is an effective and safe procedure. DRF recovery is seen in a minority of the patients; however, LP is an alternative to nephrectomy.

Background Treatment of palpable varicocele in infertile men with abnormal semen parameters is widely accepted, and physical examination (PE) remains a cornerstone for recommending varicocele repair. However, identification of clinical varicocele during PE can be challenging for both urology residents and consultants. Objective To compare the diagnostic accuracy of PE to color Doppler ultrasonography (CDU) for the diagnosis of varicocele in experienced and non-experienced examiners. Materials and methods Diagnostic accuracy study involving 78 patients attending a university-based infertility unit. Patients underwent scrotal PE by both experienced (over 10 years experience in male infertility) and non-experienced urologists (senior residents), and were subjected to CDU. varicocele diagnosis and varicocele grading were compared between examiner groups and to CDU. Accuracy measures were evaluated, and interobserver agreement was estimated using unweighted kappa statistics. A subgroup analysis for normal and high body mass index (BMI) was also performed for the same variables. Results Accuracy of PE for varicocele diagnosis was 63.5% with a positive predictive value (PPV) of 75.5%. The specificity and PPV of PE were higher among experienced than non-experienced urologists (82.0% CI: 74.27-88.26 and 81.1% CI: 74.39-86.44% vs 67.2% CI: 58.33-75.22 and 70.6% CI: 64.52-76.08, respectively). Agreements on varicocele diagnosis (k: 0.625 vs 0.517) and grading (k: 0.548 vs 0.418) by PE were higher among experienced than non-experienced urologists. Differences between eutrophic and overweight/obese patients were also suggested. Discussion and conclusions PE performed by infertility specialists identify patients with varicocele more precisely than non-specialists. However, PE alone has suboptimal accuracy for varicocele diagnosis. Our results indicate that PE should be followed by CDU to decrease the number of false positives and increase the diagnostic accuracy of varicocele diagnosis.

To perform a feasibility phase study of a panel of putative protein biomarkers and determine whether it can identify and predict tumor recurrence in patients with non-muscle-invasive bladder cancer (NMIBC) on follow-up. We prospectively analyzed the urine of 152 patients previously treated for NMIBC. Quantitative expression of plasminogen activator inhibitor-1 (PAI-1), DJ-1, apolipoprotein A-I (apoA-1), matrix metallopeptidase-9 (MMP-9), and interleukin-8 (IL-8) was assessed by enzyme-linked immunosorbent assay and compared amongst patients with and without bladder cancer recurrence at urine collection and during 3 years of follow-up. Tumor recurrence was confirmed by pathologic analysis. We performed a prediction analysis, excluding patients with recurrence at the start of the study, and assessed the influence of previous use of intravesical BCG on the level of biomarkers. Median follow-up time was 47 months (interquartile range 39–50 months). Sixteen patients (10.5%) were diagnosed with recurrence at the start of the study, and 21 (15.4%) were diagnosed during the study. Three biomarker proteins (apoA-1, MMP-9, and IL-8) appear to hold diagnostic potential [odds ratio (OR) = 12.9; 95% CI 3.5–47.4]; while, PAI-1 and IL-8 predict recurrence (OR = 4.1; 95% CI 1.4–11.4). Previous use of intravesical BCG did not affect biomarker levels. In the feasibility phase, the panel of urine biomarkers analyzed detected and predicted recurrence of NMIBC and provided reliable results in patients who had previously used intravesical BCG. Validation studies are required to confirm the panel clinical utility.

Objectives To develop a preoperative nomogram that would predict the risk of a postoperative complication for pheochromocytoma patients undergoing adrenalectomy using an international database. Methods We retrospectively analyzed preoperative variables and postoperative outcomes in patients who underwent adrenalectomy for pheochromocytoma in three institutions from 2000 to 2017. Internal validation of a generated nomogram was carried out with receiver operating characteristics, calibration plots, and decision curve analyses. Results A total of 153 patients who had undergone 166 adrenalectomies were included in the study. Overall, post-adrenalectomy complications were seen in 30% of patients, whereas 9.6% of patients sustained a Clavien ≥3a complication. Independent predictors of a complication were a history of hypertension, body mass index, tumor size, and Charlson Comorbidity Index score. On internal validation, the multivariable model generated a nomogram that predicted a postoperative complication or clinically hemodynamic event with an area under the curve of 0.86, showed good calibration and had an overall net benefit. Conclusions An internally validated nomogram combining body mass index, Charlson Comorbidity Index score and tumor size can predict the probability of a post-adrenalectomy complication in those with and without hypertension. The model, the first of its kind in pheochromocytoma surgery, identifies patients at risk of a postoperative complication at the time of their presentation with pheochromocytoma.

Objectives: To analyze the preoperative variables associated to the postoperative glomerular filtration rate (GFR) outcomes after nephrectomy for benign and malignant conditions, measured by the re...

While multiple studies have demonstrated that minimally invasive surgical (MIS) techniques are a safe and efficacious approach to adrenalectomy for pheochromocytomas (PC), these studies have only been small comparative studies. The aim of this multi-institutional study is to compare perioperative outcomes between open and MIS, stratified by robotic and conventional laparoscopic, techniques in the surgical management of PC. We retrospectively evaluated patients who underwent adrenalectomy for PCs from 2000 to 2017 at three different institutions. Clinical, perioperative, and pathologic parameters were analyzed using t test, Chi square, and Fisher exact statistical measures. Of the 156 adrenalectomy cases performed, 26 (16.7%) were with an open approach and 130 (83.3%) using MIS techniques. Of the MIS procedures, 41 (31.5%) were performed robotically and 89 (68.5%) performed laparoscopically without robotic assistance. Demographic and clinical parameters were similar between the open and MIS groups. Patients, who underwent MIS procedure had a lower complication rate (p = 0.04), shorter hospitalization (p = 0.02), shorter operative time (p < 0.001), and less blood loss (p = 0.002) than those who underwent open surgical resection. Conventional laparoscopic and robotic operative approaches resulted in similar complication rates, length of hospitalization, and blood loss. Our study is one of the largest cohorts comparing the perioperative outcomes between conventional laparoscopic and robotic adrenalectomies in patients with PC. Our results support that MIS techniques have potentially lower morbidity compared to open techniques, while laparoscopic and robotic approaches have similar perioperative outcomes.

Introduction: Surgical training models prepare the resident for a more ethical surgical practice as well as providing a less steep learning curve. In urology, there are well-known models of pyeloplasty simulation, urethro-vesical anastomosis and nephrectomy, which have helped in the training of urology residents (1–3). Learning laparoscopic prostatectomy is a difficult surgery and requires advanced surgical skill from the surgeon (4), requires operate without a direct view of the surgical field in a two-dimensional space and with longer instruments (5). Laparoscopic prostatectomy step by step makes the surgeon's learning curve less difficult, lead to less intraoperative complications, such as blood loss, while also enabling shorter operative time and less positive surgical margins (6). The objective of surgical models is to simulate surgical procedures in a reliable way thus preparing the surgeon for his daily practice, surgical simulations in animal models have been described to compensate for inadequate clinical exposure (7). The canine model of prostate cancer has many similarities with humans. Despite trying to develop a model that is as credible as possible, there are ethical issues in several countries, such as Brazil, that do not allow the use of live dogs for scientific experimentation and there is a difficulty in not standardizing the animals used (8, 9). The swine surgical training model is widely known, accepted and used as a valuable tool in the teaching of new surgeons (10). The porcine video laparoscopic prostatectomy model allows the urologist in training to exercise the skills required in a real surgical situation, practicing them in a single session (10). We will present an experimental model in pigs for training urology residents in laparoscopic radical prostatectomy with current techniques (11–13). The limitations found are that the prostate has no limits as well defined as in humans, the urethra is long and coiled, the fat surrounding the pelvic organs is scarce and there is no postoperative follow-up for evaluating functionality after the procedure, as well as the effectiveness of the surgery with surgical margins. However, it is similar in surgical model presented, it is reproducible and can provide a realistic simulation environment to the beginner surgeon. Material and Methods: In this paper, according to the institutional protocol approved by the institutional ethics and research committee FMUSP n° 964/2017 and protocol was in accordance with current international regulations for the use of animals in Research: Reporting In Vivo Experiments (ARRIVE) guide. Ten male pigs weighing 20 to 22kg were used. The animals were anesthetized with a combination of Telazol (5mg/kg), Xylazine (1.5mg/kg), Cetamine (22mg/kg) and Atropine (0.04mg/kg) for orotracheal intubation followed by Isoflurane (2%). Animals were euthanized at the end of the procedure with a lethal dose of KCl (2mEq/kg). The trocar insertion points were marked using the epigastric vessels and umbilical region as reference points. Initially, urethral catheterization was performed using a hydrophilic Nitinol guidewire, followed by a perineal incision to dissect the tortuous urethra of the porcine model. A malleable urethral catheter 8Fr was inserted into their bladder. The animal was placed in the Trendelenburg position inserted and 12mm trocars were inserted in its umbilical region, utilizing 10mm in the surgeon's dominant hand, 5mm in his non-dominant hand of the surgeon, and 5mm in the first assistant's trocar. The surgeon replicates the steps performed in a laparoscopic radical prostatectomy in humans, including the bladder catheterization, dissection of the anterior bladder plane, the vesicular and prostatic dissection, the suture of the dorsal venous plexus, a prostatectomy, an urethral vesical anast omosis, as well as the waterproof test, even including the performing of surgical steps using current concepts of anterior urethral suspension as the reconstruction of the posterior plane of the rhabdosphincter. Results: All steps of surgery could be reproduced in all ten porcine cases. No significant bleeding was observed and the surgical time was gradually reduced fifty percent from case one to last cases. Conclusions: The porcine model allowed the surgeon to replicate all the steps usually performed in a laparoscopic radical prostatectomy. The junior surgeons are better prepared to such difficult surgery. However, further studies will be necessary to prove the impact of the animal model presented in urological clinical practice.

Context The role of cytoreduction of adrenocortical carcinoma (ACC) remains poorly understood. Objective To analyze the impact of cytoreductive surgery of the primary tumor in patients with metastatic ACC. Design and Setting We performed a multicentric, retrospective paired cohort study comparing the overall survival (OS) in patients with metastatic ACC who were treated either with cytoreductive surgery (CR group) or without cytoreductive surgery (no-CR group) of the primary tumor. Data were retrieved from 9 referral centers in the American-Australian-Asian Adrenal Alliance collaborative research group. Patients Patients aged ≥18 years with metastatic ACC at initial presentation who were treated between January 1, 1995, and May 31, 2019. Intervention Performance (or not) of cytoreductive surgery of the primary tumor. Main outcome and measures A propensity score match was done using age and the number of organs with metastasis (≤2 or >2). The main outcome was OS, determined from the date of diagnosis until death or until last follow-up for living patients. Results Of 339 patients pooled, 239 were paired and included: 128 in the CR group and 111 in the no-CR group. The mean follow-up was 67 months. Patients in the no-CR group had greater risk of death than did patients in the CR group (hazard ratio [HR] = 3.18; 95% CI, 2.34-4.32). Independent predictors of survival included age (HR = 1.02; 95% CI, 1.00-1.03), hormone excess (HR = 2.56; 95% CI, 1.66-3.92), and local metastasis therapy (HR = 0.41; 95% CI, 0.47-0.65). Conclusion Cytoreductive surgery of the primary tumor in patients with metastatic ACC is associated with prolonged survival.

Context Von Hippel-Lindau (VHL) disease is an autosomal dominant syndrome caused by germline mutations in the VHL gene. Guidelines recommend pheochromocytoma (PHEO) biochemical screening should start at age 5 years. Objective Genotype–phenotype correlations in VHL, focusing on PHEO penetrance in children, were studied. Design We retrospectively evaluated 31 individuals (median age at diagnosis was 26 years) with diagnosed VHL disease. Results PHEO was diagnosed in six children with VHL. A large PHEO (5 cm) was detected in a 4-year-old boy with p.Gly114Ser mutation. PHEO penetrance was 55% starting at age 4 years. VHL missense mutations were identified in 11 of 22 families (50%), frameshift mutations in four (18.2%), stop codon in three (13.6%), splicing site in two (9.1%), and large gene deletion in two (9.1%). The codon 167 (n = 10) was a hotspot for VHL mutations and was significantly associated with PHEO (90% vs. 38%; P = 0.007). PHEOs and pancreatic neuroendocrine tumors (PNETs) were strongly associated with VHL missense mutations compared with other mutations (89.5% vs. 0% and 73.7% vs. 16.7%; P = 0.0001 and 0.002, respectively). In contrast, pancreatic cysts (91.7% vs. 26.3%; P = 0.0001), renal cysts (66.7% vs. 26.3%; P = 0.027), and central nervous system hemangioblastomas (91.7% vs. 47.3%; P = 0.012) were more frequent in VHL with nonmissense mutations. Conclusion VHL missense mutations were highly associated with PHEO and PNETs. Our data support that in children with VHL harboring missense mutations, biochemical screening for PHEO should be initiated at diagnosis.

Objectives To systematically summarize the available evidence concerning the impact of pyeloplasty on symptoms and differential renal function (DRF) in adults with unilateral UPJO in poorly functioning kidneys (PFK), and to identify potential predictors of kidney function recovery that could help clinicians select candidates for pyeloplasty. Methods A literature search (MEDLINE, Embase, Google Scholar, Scopus, ClinicalTrials.gov, and the WHO Clinical Trials Registry) and systematic review were performed up to September 2020 according to the PRISMA guidelines. PFK were defined as a baseline DRF ≤30% on renal scintigraphy. The primary endpoints were symptom relief and postoperative scintigraphic DRF. Predictors of kidney function recovery were evaluated and compared among studies. Results Nine studies comprising 731 patients met the inclusion criteria and were included for evidence synthesis. A DRF increase >5% occurred in 13.3%-53.8% of 160 patients with a pre- and postoperative renal scan. Symptoms improved in 73.3%-93.3% of 141 adults after pyeloplasty. Neither patient's age, baseline DFR, comorbidities, degree of hydronephrosis, kidney parenchymal thickness, nor kidney biopsy findings consistently predicted a significant DRF increase among 375 patients undergoing pyeloplasty. Conclusion Based on a low level of evidence, pyeloplasty may relieve symptoms and stabilize kidney function in adults with UPJO in PFK. A significant number of patients showed a DRF increase >5%, yet no consistent predictor of kidney function recovery was identified. Until more evidence becomes available, pyeloplasty could be considered for selected cases after accounting for the risks of a failure requiring a future nephrectomy.

To compare symptom resolution and short-term renal function after pyeloplasty or nephrectomy in adults with ureteropelvic junction obstruction (UPJO) in poorly functioning renal units (PFRU).Retrospective analysis of adult patients with UPJO and differential renal function (DRF) ≤ 15% who underwent laparoscopic pyeloplasty or nephrectomy. Primary endpoints included symptom resolution and estimated glomerular filtration rate (eGFR) at 12 months. Surgical complications were compared between groups. A secondary analysis was performed comparing baseline and postoperative DRF to evaluate the PFRU recovery potential after pyeloplasty.Sixty-three patients were included; 19 underwent pyeloplasty and 44 underwent nephrectomy. The mean age of the cohort was 39.5 ± 13.8 years. Nephrectomy was associated with significantly higher intra-operative blood loss (Pyeloplasty can be considered for selected patients with UPJO in PFRU as an organ-sparing alternative to nephrectomy. Although there was no significant gain in mean DRF, pyeloplasty prevented further functional loss and relieved symptoms in most cases in the short-term with at least the same complication rates of nephrectomy.

The infection by COVID-19 is a serious global public health problem. An efficient way to improve this disease's clinical management would be to characterize patients at higher risk of progressing to critically severe infection using prognostic biomarkers. The telomere length could be used for this purpose. Telomeres are responsible for controlling the number of maximum cell divisions. The telomere length is a biomarker of aging and several diseases. We aimed to compare leukocyte telomere length (LTL) between patients without COVID-19 and patients with different clinical severity of the infection. Were included 53 patients who underwent SARS-CoV-2 PCR divided in four groups. The first group was composed by patients with a negative diagnosis for COVID-19 (n = 12). The other three groups consisted of patients with a confirmed diagnosis of COVID-19 divided according to the severity of the disease: mild (n = 15), moderate (n = 17) and severe (n = 9). The LTL was determined by Q-PCR. The severe group had the shortest LTL, followed by the moderate group. The negative and mild groups showed no differences. There is an increase of patients with hypertension (p = 0.0099) and diabetes (p = 0.0067) in moderate and severe groups. Severe group was composed by older patients in comparison with the other three groups (p = 0.0083). Regarding sex, there was no significant difference between groups (p = 0.6279). In an ordinal regression model, only LTL and diabetes were significantly associated with disease severity. Shorter telomere length was significantly associated with the severity of COVID-19 infection, which can be useful as a biomarker or to better understand the SARS-CoV-2 pathophysiology., Highlights ● Telomere length is a biomarker in several diseases, including infections. ● Experimental report that associated leukocyte telomere length with severity of SARS-CoV-2. ● Leukocyte telomere length could be used to stratify patients with a greater risk of severe illness.

Purpose This prospective study presents the results of a new approach in the treatment of primary macronodular adrenal hyperplasia (PMAH), with simultaneous total adrenalectomy of the larger adrenal gland and partial adrenalectomy of the contralateral adrenal gland (adrenal-sparing surgery). Materials and Methods We performed a prospective study including 17 patients with PMAH treated surgically with adrenal-sparing surgery in a tertiary referral hospital, with a median follow-up of 41 months. Clinical, hormonal, and genetic parameters were evaluated before surgery and during follow-up. All patients had at least 1 radiological examination before and after the procedure. Results Among the 17 patients, all but 1 patient had complete hypercortisolism control, and 12 recovered normal adrenal function after surgery. Significant improvement in clinical parameters was observed: weight loss (P = .004); reduction of both systolic (P = .001) and diastolic (P = .001) blood pressure; and reduction in the number of antihypertensive drugs (P < .001). Intra-, peri-, and postoperative complications were not observed. Conclusion Adrenal-sparing surgery is a safe and feasible procedure to treat patients with PMAH, providing a substantial chance of hypercortisolism control without the disadvantages of lifetime corticosteroid replacement.

Background and Purpose: COVID-19 (Coronavirus Disease - 2019) represents a public health emergency because of the elevated transmission rates and associated mortality. There is an urgent need to limit the spread of the virus and to develop an effective antiviral treatment for the patients harboring such disease. This meta-analysis aimed to evaluate the results of the existing randomized clinical trials assessing the use of Hydroxychloroquine (HCQ) to treat COVID-19.Methods: A systematic review was performed on PubMed and Google Scholar according to the Preferred Reporting Items for Systematic Review and Meta-analysis (PRISMA) recommendations. Information from randomized controlled trials (RCT) was retrieved and included in a meta-analysis.Results: Among 214 studies that were found, 3 were included for in the meta‐ analysis. Patients treated with HCQ had a faster clearance of virus or pneumonia improvement than those that received standard treatment (OR = 7.08, 95% CI 2.79 to 4.12; P = 0.001). Only minor side effects were reported.Conclusions: Although this meta-analysis has found favorable evidence for the use of HCQ in the treatment of COVID-19, the literature does not yet present well-designed clinical studies that demonstrate the effectiveness of this medication. We believe that clinical trials coordinated by standardized guidelines, with complete and quality information, must be carried out worldwide and are urgently needed.

Background: Aldosterone producing adenomas (APAs) are the most common cause of unilateral primary aldosteronism (PA). In most cases, APAs present as small ( Clinical Cases: Case 1. A 33-yr-old man was referred to investigate resistant hypertension (HT). Biochemical evaluation revealed normal K levels, aldosterone (A) of 14.7 ng/dl, renin of 2.1 mUI/L (normal, 4.4-46.1) and A/R ratio of 24.8. Confirmatory testing confirmed PA diagnosis. Hypercortisolism investigation revealed a non-suppressible cortisol after an overnight 1 mg low-dose dexamethasone suppression (8.3 μg/dL), abnormal midnight salivary cortisol, and normal urinary free cortisol, plasma DHEAS and ACTH levels. Computed tomography (CT) scan showed a well-limited mass in left adrenal, measuring 5.8 cm with pre-contrast density of 30 HU and absolute wash-out of 72%. After left laparoscopic adrenalectomy, hydrocortisone was started and adrenal insufficiency confirmed by basal cortisol 1/3 diffuse architecture). CYP11B2 staining was positive in 30% and Ki67 in 5% of the cells. She presented biochemical cure of PA and improvement in HT control. Genetic investigation for somatic KCNJ5, ATP1A1, ATP2B3 and CTNNB1 was negative in both cases. Conclusion: We describe two rare cases of APAs that presented as large and suspicious tumors, without somatic mutations in genes associated with APAs.

Objective To determine the predictors of early, intermediate and late biochemical recurrence (BR) following minimally invasive radical prostatectomy in patients with localized prostate cancer (PC). Material and methods We included 6195 patients with cT1-3N0M0 prostate cancer treated using radical laparoscopic prostatectomy (RLP) and radical robot-assisted prostatectomy at our institution between 2000 and 2016. None of the patients underwent adjuvant therapy. BR is defined as PSA levels ≥0.2 ng/dL. The time to BR is divided into terciles to identify the variables associated with early ( 36 months) recurrence. We employed logistic regression models to determine the risk factors associated with each interval. Results We identified 1148 (18.3%) patients with BR. The median time to BR was 24 months (IQR, 0.98–53.18). The multivariate analysis showed that preoperative PSA levels, lymph node invasion, positive margins and RLP are associated with early recurrence (p ≤ 0.029 for all). Laparoscopic surgery was the only predictor of intermediate recurrence (p = 0.001). The predictors of late recurrence included a pathological Gleason score ≥7, stage ≥pT3, positive margins and RLP (p ≤ 0.02 for all). Conclusions The patients with high-risk prostate cancer can develop late recurrence and require long-term follow-up. Identifying patients with higher PSA levels and lymph node invasion has an important predictive role in the first year after surgery. The association between RLP and BR warrants further assessment.

Background Radical prostatectomy (RP) has been used as the main primary treatment for prostate cancer (PCa) for many years with excellent oncologic results. However, approximately 20-40% of those patients has failed to RP and presented biochemical recurrence (BCR). Prostatic specific antigen (PSA) has been the pivotal tool for recurrence diagnosis, but there is no consensus about the best PSA threshold to define BCR until this moment. The natural history of BCR after surgical procedure is highly variable, but it is important to distinguish biochemical and clinical recurrence and to find the correct timing to start multimodal treatment strategy. Also, it is important to understand the role of each clinical and pathological feature of prostate cancer in BCR, progression to metastatic disease and cancer specific mortality (CSM). Review design A simple review was made in Medline for articles written in English language about biochemical recurrence after radical prostatectomy. Objective To provide an updated assessment of BCR definition, its meaning, PCa natural history after BCR and the weight of each clinical/pathological feature and risk group classifications in BCR, metastatic disease and CSM.

Introduction: Urethral duplication is rare. Characterized by the presence of two urethral channels. This anomaly presents a great variety of clinical findings that depend on the type of duplication that often is associated with other anomalies. Material and Methods: We report thirteen boys with urethral duplication managed in our institution between 1988-2015. Clinical findings, associated anomalies, treatment of urethral duplication and our results are described. Patients were classified according to Effmann classification. Results: Mean patient's age was 38.3±34.7 months (3-136 months). Mean follow-up was 7.7±3.4 years (3y8m-14y2m). Type II A2 was the most common pattern (8/13 patients, 61.5%), followed by type IA (3/13 patients, 23%) and IIA1 (2/13 patients, 15.3%). The most frequent clinical manifestations were urinary tract infections (UTI) observed in 11/13 patients (84.6%) and anal urinary leakage, found in 7/13 patients (53.8%). Associated anomalies were found in 9/13 patients (69.2%). Required surgeries were 3.53±2.84 procedures per patient. Considering groups: Type IIA2 4.25±3.28, type IIA1 4±1.41 and type IA 1.33±0.57 needed procedures per patient. Complications rate were 0% for type IA, 50% for type IIA1 and 75% for type IIA2. Conclusions: Patients with incomplete duplication (type I A or I B) can totally be asymptomatic, with no need of surgical correction. Type IIA2 is the most complex form of duplication to correct and multiple procedures might be required because of the very hypoplastic orthotopic dorsal urethral tissue. Surgical treatment should be individualized and parents should be advised on complications and need of multiple surgeries according to urethral duplication type.

We assessed the impact of focal therapy on perioperative, oncologic and functional outcomes in men who underwent salvage robotic assisted radical prostatectomy compared to primary robotic assisted radical prostatectomy.Focal therapy was performed in patients presenting with Gleason score 3 + 3 or 3 + 4, clinical stage cT2a or less, serum prostate specific antigen 15 ng/ml or less, unilateral positive biopsy, maximum length of any positive core less than 10 mm and life expectancy greater than 10 years. Focal therapy was defined as target ablation of the index lesion plus a 1 cm safety margin in the normal ipsilateral prostatic parenchyma. The salvage group included 22 men who underwent salvage prostatectomy after focal therapy failure. The primary group was defined using matched pair 1:2 selection of 44 of 2,750 patients treated with primary prostatectomy. The primary and secondary end points were the between group differences in functional and oncologic outcomes, respectively.Complication rates were comparable (p0.05). Pad-free probability was comparable between the groups at 1 and 2 years (p = 0.8). Recovery of erectile function was significantly lower after salvage robotic assisted radical prostatectomy (p = 0.008), which also showed a significantly lower probability of cumulative biochemical recurrence-free survival compared to primary robotic assisted radical prostatectomy (56.3% vs 92.4% at 2 years, p = 0.001). Salvage prostatectomy demonstrated a significantly increased risk of biochemical recurrence (HR 4.8, 95% CI 1.67-13.76, p = 0.004). Study limitations included the retrospective nature, the lack of randomization and the short followup.Salvage robotic assisted radical prostatectomy after focal therapy failure is feasible with acceptable complication rates. However, patients assigned to primary focal therapy should be advised about a poorer prognosis in terms of oncologic control and lower erectile recovery rates in case of a future salvage surgery.

Purpose To evaluate whether patients with prostate cancer have worse functional urinary recovery with focal brachytherapy (FBT) at the base versus the apex of the prostate. Methods and Materials The functional outcomes of patients treated with FBT at the base of the prostate were compared with those of patients treated with FBT at the apex. Urinary symptoms, continence, and erectile dysfunction were measured using the International Prostate Symptom Score (IPSS), International Continence Score (ICS), and International Index of Erectile Function (IIEF-5) questionnaires, respectively, at baseline and at 6, 12, and 24 months after treatment. Results Twenty-eight and 13 patients were treated with FBT at the apex and the base, respectively, of the prostate. A significant difference between groups was found in the IPSS score at 6 months (mean IPSS: apex 6.4 ± 4.7, base 10.6 ± 5.7; p = 0.02), but not at baseline or at 12 and 24 months after treatment. On multivariate analysis, only FBT at the base of the prostate remained an independent predictor of worsening urinary symptoms (odds ratio, 5.8; p = 0.04). Conclusions At 6 months after FBT, significantly less urinary toxicity was found in patients who underwent FBT at the apex versus the base of the prostate. Continence and sexual side effects were minimal in all patients.

Adrenocortical carcinoma (ACC) is a rare endocrine malignancy with an unfavorable prognosis. Despite the poor prognosis in the majority of patients, no improvements in treatment strategies have been achieved. Therefore, the discovery of new prognostic biomarkers is of enormous interest. Sterol-O-acyl transferase 1 (SOAT1) is involved in cholesterol esterification and lipid droplet formation. Recently, it was demonstrated that SOAT1 inhibition leads to impaired steroidogenesis and cell viability in ACC. To date, no studies have addressed the impact of SOAT1 expression on ACC prognosis and clinical outcomes. We evaluated SOAT1 expression by quantitative real-time polymerase chain reaction and immunohistochemistry in a tissue microarray of 112 ACCs (Weiss score &ge, 3) from adults treated in a single tertiary center in Brazil. Two independent pathologists evaluated the immunohistochemistry results through a semiquantitative approach (0&ndash, 4). We aimed to evaluate the correlation between SOAT1 expression and clinical, biochemical and anatomopathological parameters, recurrence-free survival (RFS), progression-free survival (PFS), and overall survival (OS). SOAT1 protein expression was heterogeneous in this cohort, 37.5% of the ACCs demonstrated a strong SOAT1 protein expression (score &gt, 2), while 62.5% demonstrated a weak or absent protein expression (score &le, 2). Strong SOAT1 protein expression correlated with features of high aggressiveness in ACC, such as excessive tumor cortisol secretion (p = 0.01), an advanced disease stage [European Network for the Study of Adrenal Tumors (ENSAT) staging system 3 and 4 (p = 0.011)] and a high Ki67 index (p = 0.002). In multivariate analysis, strong SOAT1 protein expression was an independent predictor of a reduced OS (hazard ratio (HR) 2.15, confidence interval (CI) 95% 1.26&ndash, 3.66, p = 0.005) in all patients (n = 112), and a reduced RFS (HR 2.1, CI 95% 1.09&ndash, 4.06, p = 0.027) in patients with localized disease at diagnosis (n = 83). Our findings demonstrated that SOAT1 protein expression has prognostic value in ACC and reinforced the importance of investigating SOAT1 as a possible therapeutic target for patients with ACC.

Purpose: To investigate risk factors for complications in patients undergoing adrenalectomy. Materials and Methods: A retrospective search of our institutional database was performed of patients who underwent adrenalectomy, between 2014 and 2018. Clinical parameters and adrenal disorder characteristics were assessed and correlated to intra and post-operative course. Complications were analyzed within 30-days after surgery. A logistic regression was performed in order to identify independent predictors of morbidity in patients after adrenalectomy. Results: The files of 154 patients were reviewed. Median age and Body Mass Index (BMI) were 52-years and 27.8kg/m2, respectively. Mean tumor size was 4.9±4cm. Median surgery duration and estimated blood loss were 140min and 50mL, respectively. There were six conversions to open surgery. Minor and major post-operative complications occurred in 17.5% and 8.4% of the patients. Intra-operative complications occurred in 26.6% of the patients. Four patients died. Mean hospitalization duration was 4-days (Interquartile Range: 3-8). Patients age (p=0.004), comorbidities (p=0.003) and pathological diagnosis (p=0.003) were independent predictors of post-operative complications. Tumor size (p

Purpose To describe the surgical treatment of a patient harboring a ureteropelvic junction obstruction (UPJO) in the lower unit of an incomplete duplicated collecting system. Methods A female patient with 32-years old presented a progressively increasing left lumbar pain for 1 year and urinary tract infections (UTI) for the past 10 years. Computed tomography demonstrated a UPJO in the lower unit of an incomplete duplicated urinary collecting system. Results The patient underwent a robot-assisted pyeloureterostomy. The surgical time was 118 minutes and there was no intraoperative complication. During surgery, anomalous vessels crossing to the lower pole of the kidney were identified. The bladder catheter and abdominal drain were removed at the first and second postoperative days. The length of the hospital stay was 2 days and the post-operative course was uneventful. The double-J stent was retrieved 4 weeks after surgery. At 18 months of follow-up, the patient had complete pain resolution and no new episodes of UTI. The control image exam revealed minimal residual hydronephrosis. Conclusion Robot-assisted pyeloureterostomy was an effective approach to the present case. Many times, the surgical strategy for patients with anatomic variants is determined intra-operatively. The surgeon must have a wide range of skills and be prepared for a timely decision.

OBJECTIVE To estimate the conditional biochemical recurrence-free probability and to develop a predictive model according to the disease-free interval for men with clinically localized prostate cancer treated with minimally invasive radical prostatectomy. METHODS The study population consisted of 3576 consecutive patients who underwent laparoscopic radical prostatectomy and 2619 men treated with robotic radical prostatectomy in the past 15 years at Institute Mutualiste Montsouris, Paris, France. Biochemical recurrence was defined as serum prostate-specific antigen ≥0.2 ng/dL. Univariable and multivariable survival analyses were carried out to identify the prognostic factors for overall free-of-biochemical recurrence probability and conditional survival with respect to the years from surgery without recurrence. A detailed nomogram for the static and dynamic prognosis of biochemical recurrence was developed and internally validated. RESULTS The median follow-up period was 8.49 years (interquartile range 4.01-12.97), and 1148 (19%) patients experienced biochemical recurrence. Significant variables associated with biochemical recurrence in the multivariable model included preoperative prostate-specific antigen, positive surgical margins, extracapsular extension, pathological Gleason ≥4 + 3 and laparoscopic surgery (all P

A 19-year-old female patient presented refractory disabling loin pain associated with mild kidney atrophy (split renal function of 33%). Investigation revealed elevated serum renin level; a therapeutic test with oral renin inhibitor was tried, obtaining important pain control. Aiming to resolve the symptom while preserving the patient kidney and attributing the pain mechanism to be associated with the abnormal renin production, a laparoscopic kidney denervation was performed with no complications and complete pain resolution.

The participation of aberrant receptors and intra-adrenal ACTH in hyperplastic tissue are considered mechanisms that regulate hypercortisolism in PMAH. Additionally, germline ARMC5 mutations have been described as the most frequent genetic abnormality found in patients diagnosed with PMAH. Previous functional studies analyzed ARMC5 role using H295R cells. Therefore, we investigated the role of ARMC5 in cell cultures obtained from PMAH nodules containing steroidogenic cells, aberrant receptors and intra-adrenal ACTH. ARMC5 silencing in non-mutated PMAH cell cultures decreased steroidogenesis-related genes and increased CCNE1 mRNA expression and proliferative capacity without affecting cell viability. Additionally, ARMC5 overexpression induced cell death in PMAH mutated cell cultures, thereby decreasing cell viability. We confirmed the role of ARMC5 as an important pro-apoptotic protein involved in PMAH-related steroidogenesis. We also report for the first time the involvement of ARMC5 in controlling proliferation and regulating cell cycle in PMAH cell cultures; these effects need to be explored further.

Purpose: To evaluate the role of ARDT after surgical resection of ACC. Materials and Methods: Records of patients from our institutional ACC database were retrospectively assessed. A paired comparison analysis was used to evaluate the oncological outcomes between patients treated with surgery followed by ARDT or surgery only (control). The endpoints were LRFS, RFS, and OS. A systematic review of the literature and meta-analysis was also performed to evaluate local recurrence of ACC when ARDT was used. Results: Ten patients were included in each Group. The median follow-up times were 32 months and 35 months for the ARDT and control Groups, respectively. The results for LRFS (p=0.11), RFS (p=0.92), and OS (p=0.47) were similar among subsets. The mean time to present with local recurrence was significantly longer in the ARDT group compared with the control Group (419±206 days vs. 181±86 days, respectively; p=0.03). ARDT was well tolerated by the patients; there were no reports of late toxicity. The meta-analysis, which included four retrospective series, revealed that ARDT had a protective effect on LRFS (HR=0.4; CI=0.17-0.94). Conclusions: ARDT may reduce the chance and prolong the time to ACC local recurrence. However, there were no benefits for disease recurrence control or overall survival for patients who underwent this complementary therapy.

To evaluate predictive factors associated with detectable prostate-specific antigen (PSA) and describe clinical recurrence (CR) and cancer-specific mortality (CSM) after robot-assisted radical prostatectomy (RARP). The study included 2500 patients who were treated with RARP at a single institution between 2000 and 2016. All patients had clinically localized PCa. Patients were divided into two groups according to PSA value at 6 weeks after surgery: undetectable (n = 2271; PSA

Robot-assisted radical prostatectomy (RARP) has been embraced by urologists and has become a treatment standard in many countries already. Learning how to perform a RARP is challenging and has not yet been standardized. The current review summarizes the latest concepts regarding the most effective way of training for RARP.The strategy to learn RARP should comprise didactic activities, skills lab training, participating in surgeries and mentorship. Skills lab and virtual simulators are valuable tools to develop manual abilities and to overcome the initial technical learning curve. Participating in surgeries is crucial for familiarization with the robot installation, steps of the surgical procedure and is essential for troubleshooting. Mentorship improves learning and is the safest way to initiate real practice. Innate and individual background variances were suggested to influence the learning process; however, there is paucity of robust evidence correlating previous surgical experience and, for example videogame playing with faster learning of RARP. Structured curricula were proposed to orient the training for robotic surgery; currently, only one is focused exclusively on urology.Systematic training is the most effective way to learn and surpass the possibly intense learning curve of RARP. Training activities should focus on developing cognitive and manual abilities. The existing curricula for robotic surgery training still require constant refinement; however, they offer good and structured guidance to train for RARP.

A young patient from central Africa presented acute renal insufficiency due to extrinsic compression of the distal ureters by a pelvic mass. After initial medical management, a biopsy revealed poorly differentiated bladder cancer and Schistosoma haematobium eggs embedded in the bladder wall. The initial workup showed evidence of locoregional disease. Radical cystectomy with an incontinent urinary diversion was performed with no complications. Carcinosarcoma of the bladder was diagnosed by pathological analysis of the surgical specimen. After a short follow-up, the patient was readmitted presenting with lung and bone metastases. At 60 days after diagnosis, he died of respiratory insufficiency caused by pulmonary metastatic disease.

Objective To determine the feasibility and safety of performing robotic-assisted laparoscopic urological surgery (RALS) in infants and young children, highlighting technical challenges posed by the smaller body size and their potential solutions. Patients and methods We retrospectively reviewed perioperative records of all patients less than 3 years of age who underwent RALS at our institution between January 2006 and October 2012. Intraoperative data included difficulties with the robotic instruments or surgical procedure. Post-operative data included length of hospital stay and any complications. Results A total of 65 children less than 3 years underwent RALS. The average patient age was 1.6 years ± 0.7, with 14 patients under 1 year of age. Median patient weight was 11.6 kg ± 2.5 kg. Mean operative time was 153.3 ± 57 min. No conversions to open technique or intra-operative complications were reported. A total of 12 post-operative complications were identified after a mean follow-up of 13.6 months: 7 early complications and 5 late complications. Smaller children did not have more complications than larger children. Conclusion There are inherent challenges with performing RALS in infants and young children. However, they may be overcome with specific technical maneuvers and through understanding of the limitations of the robotic system.

The objective of this study is to evaluate the diagnostic properties of urinary biomarkers in adults with ureteropelvic junction obstruction: KIM-1, NGAL, CA19-9, and β2-microglobulin. We also assessed urinary biomarker concentrations following pyeloplasty.We prospectively studied adults from December 2013 to February 2015. We included 47 patients with a mean age of 38.6 ± 12.7 years. Each patient provided four samples of voided urine for biomarker measurement, one at pre-operative consultation and the others at 1, 3, and 6 months of post-operative follow-up. The control group consisted of 40 healthy individuals with no hydronephrosis on ultrasound evaluation.KIM-1 had an area under the curve of 0.79 (95% CI 0.70-0.89), NGAL 0.71 (95% CI 0.61-0.83), CA19-9 0.70 (95% CI 0.60-0.81), and β2-microgloblin 0.61 (95% CI 0.50-0.73). KIM-1 was the most sensitive marker with a cut-off of 170.4 pg/mg creatinine (sensitivity 91.4%, specificity 59.1%), whereas CA19-9 was the most specific with a cut-off of 51.3 U/mg creatinine (sensitivity 48.9%, specificity 88.0%). Urinary concentrations of biomarkers decreased after pyeloplasty.The evaluation of urinary biomarkers is useful in adults undergoing pyeloplasty. KIM-1, NGAL, and CA19-9 were elevated and significantly decreased after surgery.

Prostate cancer (PCa) is stratified into different risk categories based on the patient's prognosis. High-risk disease was formerly characterized by an increased risk of metastasis and lethality, requiring complex treatments. Surgery was recently highlighted to have a pivotal role for the treatment of such cases, even as monotherapy. In the past, open radical prostatectomy was performed for most patients with high-risk PCa; however, robot-assisted radical prostatectomy (RARP) emerged as a reasonable option because it provided optimal outcomes for low- and intermediate-risk PCa. Robust studies are lacking to properly assess the role of RARP for high-risk PCa. We summarize this knowledge and present a literature review on the perioperative recovery and functional and oncologic outcomes of RARP for the treatment of patients with high-risk PCa.

To perform a meta-analysis comparing the rates of positive surgical margins (PSM) and biochemical recurrence (BCR) between open radical prostatectomy (ORP) and robot-assisted radical prostatectomy (RARP) in patients with high-risk prostate cancer. A systematic review was performed on Pubmed, Embase and Scopus databases in August 2016, according to the Preferred Reporting Items for Systematic Review and Meta-analysis (PRISMA) statement. References retrieved were evaluated using the Newcastle–Ottawa scale and the Black and Down’s tool for quality assessment. Nine retrospective cohorts comparing ORP and RARP were selected and included in the meta-analysis. All studies reported the PSMs. Patients treated with RARP presented less risk of PSMs (risk difference −0.04, p 0.02) than those treated with ORP. Five articles reported hazard ratios for BCR-free survival. Patients treated with RARP had less risk of BCR (HR 0.72, 95% CI 0.58–0.89) than those treated with ORP. Reports for PSM assessment were considered of adequate quality, while the studies retrieved for BCR assessment were considered limited because of the heterogeneity of their results. Patients with high-risk prostate cancer treated with RARP have less risk of having PSM and BCR when compared to those treated with ORP. A strong conclusion is precluded due to the observational nature of the studies retrieved for our analysis.