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Purpose: To evaluate if the density of interstitial cells of Cajal (ICC) in the ureteropelvic junction (UPJ) influences the outcomes of pyeloplasty in adults. Methods: Twenty-three patients with the diagnosis of ureteropelvic junction obstruction (UPJO) that underwent laparoscopic dismembered pyeloplasty were included. ICC density was measured using immunohistochemistry reaction for c-KIT expression in the resected UPJ segment. Pyeloplasty outcome was evaluated by patient self-report pain, urinary outflow using DTPA renogram and hydronephrosis assessment using ultrasound (US) at 12 months of follow-up. A logistic regression analysis was performed to assess the association of pyeloplasty outcomes and ICC density. Results: Low, moderate, and high ICC density were present in 17.4%, 30.4%, and 52.2% of the patients, respectively. Complete pain resolution was observed in 100%, 85.7%, and 75% of patients with low, moderate and high ICC density, respectively ( p = 0.791). DTPA renogram improved in 75%, 85.7%, and 91.7% of patients with low, moderate and high ICC density, respectively ( p = 0.739). Hydronephrosis improved in 25%, 85.7%, and 91.7% of patients with low, moderate and high ICC density, respectively ( p = 0.032). Conclusions: Patients with high ICC density have a significant amelioration of hydronephrosis after pyeloplasty. However, ICC density is not associated with functional outcomes.

ContextLimited information is available concerning the genetic spectrum of pheochromocytoma and paraganglioma (PPGL) patients in South America. Germline SDHB large deletions are very rare worldwide, but most of the individuals harboring the SDHB exon 1 deletion originated from the Iberian Peninsula.ObjectiveOur aim was to investigate the spectrum of SDHB genetic defects in a large cohort of Brazilian patients with PPGLs.MethodsGenetic investigation of 155 index PPGL patients was performed by Sanger DNA sequencing, multiplex ligation-dependent probe amplification, and/or target next-generation sequencing panel. Common ancestrality was investigated by microsatellite genotyping with haplotype reconstruction, and analysis of deletion breakpoint.ResultsAmong 155 index patients, heterozygous germline SDHB pathogenic or likely pathogenic variants were identified in 22 cases (14.2%). The heterozygous SDHB exon 1 complete deletion was the most frequent genetic defect in SDHB, identified in 8 out of 22 (36%) of patients. Haplotype analysis of 5 SDHB flanking microsatellite markers demonstrated a significant difference in haplotype frequencies in a case-control permutation test (P = 0.03). More precisely, 3 closer/informative microsatellites were shared by 6 out of 8 apparently unrelated cases (75%) (SDHB-GATA29A05-D1S2826-D1S2644 | SDHB-186-130-213), which was observed in only 1 chromosome (1/42) without SDHB exon 1 deletion (X2 = 29.43; P < 0.001). Moreover, all cases with SDHB exon 1 deletion had the same gene breakpoint pattern of a 15 678 bp deletion previously described in the Iberian Peninsula, indicating a common origin.ConclusionThe germline heterozygous SDHB exon 1 deletion was the most frequent genetic defect in the Brazilian PPGL cohort. Our findings demonstrated a founder effect for the SDHB exon 1 deletion in Brazilian patients with paragangliomas.

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.

COVID-19 represents a public health emergency, whose mechanism of which is not fully understood. It is speculated that microRNAs may play a crucial role in host cells after infection by SARS-CoV-2. Thus, our study aimed to analyze the expression of miR-200c-3p in saliva samples from patients with COVID-19. One handred eleven samples from patients with COVID-19 were divided into 4 groups. Group I: 39 patients negative for Covid-19; Group II: 37 positive and symptomatic patients, with no indication of hospitalization; Group III: 21 patients with respiratory disorders (hospitalized); Group IV: 14 patients with severe conditions (oxygen therapy). The expression levels of miR-200c-3p were determined using qPCR. We found greater expression of miR-200c-3p in patients in group IV (p

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.

Context Primary aldosteronism (PA) screening relies on an elevated aldosterone to renin ratio with a minimum aldosterone level, which varies from 10 to 15 ng/dL (277-415.5 pmol/L) using immunoassay. Objective To evaluate intra-individual coefficient of variation (CV) of aldosterone and aldosterone to direct renin concentration ratio (A/DRC) and its impact on PA screening. Methods A total of 671 aldosterone and DRC measurements were performed by the same chemiluminescence assays in a large cohort of 216 patients with confirmed PA and at least 2 screenings. Results The median intra-individual CV of aldosterone and A/DRC was 26.8% and 26.7%. Almost 40% of the patients had at least one aldosterone level 2 ng/dL/µIU/mL had a true positive rate for PA diagnosis of 94.4% and 98.4% when based on 1 or 2 assessments, respectively. CV of aldosterone and A/DRC were not affected by sex, use of interfering antihypertensive medications, PA lateralization, hypokalemia, age, and number of hormone measurements. Conclusion Aldosterone concentrations had a high CV in PA patients, which results in an elevated rate of false negatives in a single screening for PA. Therefore, PA screening should be based on at least 2 screenings with concomitant aldosterone and renin measurements.

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.

Female patient, 37 years old, coming from China, with a history of resistant arterial hypertension since the age of 25 years old associated with spontaneous hypokalemia and classic ACTH-independent Cushing's syndrome. Radiological imaging exams showed bilateral adrenal nodules. Diagnosed primary hyperaldosteronism (Baseline aldosterone 103ng/dL (2.5-39.2), Renin 2.7uUI/mL (4.4 - 46.1), Aldo/renin ratio 38.1 and K 3.3) and confirmed laboratory hypercortisolism (Cortisol after 1mg of dexamethasone overnight 17.9mcg/Dl (< 1.8), salivary cortisol at midnight 0.466mcg/dL ( Presentation: No date and time listed

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.

A hiperplasia prostática benigna (HPB) é uma das doenças mais frequentes do homem. Devido à alta prevalência, considera-se uma condição natural do envelhecimento masculino. Nem todos os pacientes com HPB terão sintomas relacionados à alteração prostática.

Adrenocortical carcinoma (ACC) is a rare malignancy that is associated with a dismal prognosis. Pan-genomic studies have demonstrated the involvement of ATRX and ZNRF3 genes in adrenocortical tumorigenesis. Our aims were to evaluate the protein expression of ATRX and ZNRF3 in a cohort of 82 adults with ACC and to establish their prognostic value. Two pathologists analyzed immuno-stained slides of a tissue microarray. The low protein expression of ATRX and ZNRF3 was associated with a decrease in overall survival (OS) (p = 0.045, p = 0.012, respectively). The Cox regression for ATRX protein expression of >1.5 showed a hazard ratio (HR) for OS of 0.521 (95% CI 0.273–0.997; p = 0.049) when compared with ≤1.5; for ZNRF3 expression >2, the HR for OS was 0.441 (95% CI, 0.229–0.852; p = 0.015) when compared with ≤2. High ATRX and ZNRF3 protein expressions were associated with optimistic recurrence-free survival (RFS) (p = 0.027 and p = 0.005, respectively). The Cox regression of RFS showed an HR of 0.332 (95%CI, 0.111–0.932) for ATRX expression >2.7 (p = 0.037), and an HR of 0.333 (95%CI, 0.140–0.790) for ZNRF3 expression >2 (p = 0.013). In conclusion, low protein expression of ATRX and ZNRF3 are negative prognostic markers of ACC; however, different cohorts should be evaluated to validate these findings.

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.

Introduction: Masses in adrenal topography are diagnosed frequently due to the increase in radiological imaging in clinical practice. Adrenal incidentalomas occur between 4% and 10% of the patients above 50 years undergoing abdominal imaging, and the majority are benign pathologies. Objective: To analyze the characteristics of the masses located in adrenal gland topography not originating from the adrenal gland. Methods: We retrospectively assessed patients from our tertiary hospital who underwent surgical treatment for masses in adrenal gland topography between 2006 and 2018. All patients had hormonal evaluations, according to the European and American Societies of Endocrinology guidelines. Two expert radiologists reviewed all images. Forty-six patients were included in the study, and the surgical specimens were analyzed by the same experienced pathologist. Patients with confirmed adrenocortical carcinoma (ACC) were excluded from this cohort. Results: Thirty-two (69.6%) patients were female. The median age was 49.5 years old (range 18-82yo). Abdominal or lumbar pain was the most frequent reason for medical investigation (43.5%). Adrenal incidentalomas represented 38.4% of the cohort. None of these patients had any clinical signs of adrenal hyperfunction, nor hormonal alteration. Twenty-four patients (52.17%) presented a mass on the left side, and only two cases presented bilateral adrenal masses. The median size was 8.6cm (1.3-18cm). The mean of Hounsfield Units (HU) on a non-contrasted CT was 25HU (0-50HU). Several etiologies were found: 8 cases (18%) of ganglioneuroma; 6 cases (13,5%) of adrenal cysts; 4 cases (9%) of leiomyosarcoma and adrenal hemorrhage; 3 cases (6.5%) of infectious disease; 2 cases (4.5%) of lymphangioma, schwannoma, and sarcoma. We also found single cases of renal cell carcinoma, poorly differentiated small cell neuroendocrine carcinoma, hepatocellular carcinoma, high grade dedifferentiated liposarcoma, epithelioid neoplasia, epithelial neoplasia with neuroendocrine differentiation, malignant peripheral nerve sheath tumor of the adrenal gland, poorly differentiated neuroblastoma, high grade lymphoma, myelolipoma, acute splenitis, arteriovenous malformation, and prostate cancer metastasis. Discussion and Conclusion: Ganglioneuroma was the most frequent diagnosis in adrenal incidentalomas in our cohort. In general, these conventional radiological exams could not differentiate lesions originated in the adrenal glands from lesions of other origins. In this large cohort, we could identify non-adrenal origin in approximately 45% of the patients with masses in the adrenal topography.

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.

Introduction: Pheochromocytomas and paragangliomas (PPGLs) are rare neuroendocrine tumors arising from chromaffin cells. More than 30% of patients with PPGLs have a hereditary predisposition. Malignancy in PPGLs is defined by the presence of local invasion or metastasis in nonchromaffin tissues. Germline SDHB mutations are found in approximately 40% of malignant PPGLs, mainly paragangliomas (PGLs). However, SDHB mutations are not a prognostic factor in malignant PPGLs. To date, no genotype-phenotype correlation has been reported in malignant PPGLs associated with SDHB mutations. Aim: To investigate clinical and imaging features of patients with malignant PGLs harboring germline SDHB exon 1 deletion or splicing site mutation. Methods: We retrospectively evaluated 22 unrelated individuals with malignant PPGLs. Six out of 22 (27%) malignant PPGLs harbored germline SDHB mutations. Three patients had SDHB exon 1 deletion and 3 splicing site mutation (2 with c.201-2A>G and one with c.423 + 1G>A). All SDHB defects were classified as likely pathogenic. Results: In the exon 1 deletion group, 2 patients had abdominal PGLs (one also had a neck PGL) and one had only head and neck PGLs. In the splicing site mutation group, all 3 patients had abdominal PGLs (one also had a neck PGL). Median age at diagnosis was 26 yrs (16 to 45) and 33 yrs (26 to 53) in the exon 1 deletion and splicing mutation groups, respectively. Two patients (one in each group) had metastasis at diagnosis. All 6 patients had bone metastasis, but liver and/or lung metastasis were more frequent in patients with SDHB exon 1 deletion (66 vs. 33%). Interestingly, metastasis from malignant PGLs harboring SDHB splicing site mutations were 131I-metaiodobenzylguanidine (MIBG) avid in all cases, whereas metastatic lesions from malignant PGLs harboring SDHB exon 1 deletion did not present any MIBG uptake on diagnostic imaging studies. Therefore, all 3 patients with SDHB exon 1 deletion were treated with chemotherapy (cyclophosphamide, vincristine and dacarbazine). In contrast, all 3 patients with splicing site mutations have been treated with MIBG therapy. Median follow-up was 87 months (8 to 360 months). Only one patient (exon 1deletion group) died because of disease progression. Conclusion: We first demonstrated here that germline SDHB exon 1 deletion is associated with absence of MIBG uptake in malignant PGLs. This finding needs to be confirmed in an expanded cohort of malignant PPGLs.

Background: 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, largely due to the rarity of these tumors. Therefore, the discovery of new prognostic biomarkers that could guide and improve the management of patients with ACC is of enormous interest. Sterol-O-Acyl Transferase 1 (SOAT1) is involved in cholesterol esterification in adrenocortical cells. Recently, it was demonstrated that SOAT1 inhibition leads to impaired steroidogenesis and cell viability in ACC [1]. There are no studies so far addressing the impact of SOAT1 protein expression in ACC prognosis and clinical outcomes. Methods: We evaluated SOAT1 protein expression by immunohistochemistry (ab39327; 1:4000; Abcam, EUA) in a tissue microarray of 107 adrenocortical carcinomas (Weiss score ≥ 3) from adult patients treated in a single tertiary center in Brazil. Immunohistochemistry results were evaluated through a semiquantitative approach by two independent pathologists. We aimed to evaluate the correlation of SOAT1 protein expression with clinical and biochemical parameters, surgical specimen histological characteristics, recurrence free-survival, progression free-survival and overall survival. Results: SOAT1 protein expression was heterogenous in this cohort; 38% of ACCs demonstrated strong SOAT1 protein expression while 62% demonstrated weak or absent SOAT1 protein expression. Strong SOAT1 protein expression correlates with known features of high aggressiveness in ACC, such as excessive tumor cortisol secretion (p= 0.007), advanced disease stage [ENSAT 3 and ENSAT 4 (p= 0.009)] and high Ki67 index (0.008). On multivariate analysis, strong SOAT1 protein expression was an independent predictor of lower overall survival (HR 1.71, CI 95% 1.05-2.92; p= 0.04) when considering all cases (n= 107) and of lower progression free survival (HR 3.05, CI 95% 1.05-8.85; p= 0.04) in patients with metastatic disease at diagnosis (n= 22). Conclusions: Our findings demonstrated that SOAT1 protein expression has prognostic value in ACC and reinforce the importance of investigating SOAT1 as a possible therapeutic target for patients with ACC. Multicentric prospective studies including a larger number of patients are needed in order to validate and consolidate the results found in this cohort. References: 1. Sbiera S, Leich E et al. Mitotane inhibits Sterol-O-Acyl Transferase 1 Triggering Lipid-Mediated Endoplasmic Reticulum Stress and Apoptosis in Adrenocortical Carcinoma Cells. Endocrinology. 2015; 156 (11):3895-908.

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.