FRANCISCO TIBOR DENES
Projetos de Pesquisa
Unidades Organizacionais
Instituto Central, Hospital das Clínicas, Faculdade de Medicina
LIM/55 - Laboratório de Urologia, Hospital das Clínicas, Faculdade de Medicina - Líder
LIM/55 - Laboratório de Urologia, Hospital das Clínicas, Faculdade de Medicina - Líder
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- Genetic and clinical aspects of paediatric pheochromocytomas and paragangliomas(2021) PETENUCI, Janaina; GUIMARAES, Augusto G.; FAGUNDES, Gustavo F. C.; BENEDETTI, Anna Flavia F.; AFONSO, Ana Caroline F.; PEREIRA, Maria Adelaide A.; ZERBINI, Maria Claudia N.; SIQUEIRA, Sheila; YAMAUCHI, Fernando; SOARES, Silvia C.; SROUGI, Victor; TANNO, Fabio Y.; CHAMBO, Jose L.; I, Roberto Lopes; DENES, Francisco T.; HOFF, Ana O.; LATRONICO, Ana Claudia; MENDONCA, Berenice B.; V, Maria Candida B. Fragoso; ALMEIDA, Madson Q.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.
- The role of renal biomarkers to predict the need of surgery in congenital urinary tract obstruction in infants(2019) KOSTIC, D.; BEOZZO, G. P. N. S.; COUTO, S. B. do; KATO, A. H. T.; LIMA, L.; PALMEIRA, P.; KREBS, V. L. J.; BUNDUKI, V; V, R. P. Francisco; ZUGAIB, M.; DENES, F. T.; CARVALHO, W. B. de; KOCH, V. H. K.Introduction The diagnosis of renal function impairment and deterioration in congenital urinary tract obstruction (UTO) continues to be extremely challenging. The use of new renal biomarkers in this setting may favor early renal injury detection, allowing for a reliable choice of optimal therapeutic options and the prevention or minimization of definitive renal damage. Objective The aim of the study was to investigate a selection of promising biomarkers of renal injury with the intention of evaluating and comparing their profile with clinically based decisions for surgical intervention of infants with congenital obstructive uropathies. Study design The first-year profile of renal biomarkers, serum creatinine (sCr), serum and urine cystatin C (CyC), neutrophil gelatinase-associated lipocalin (NGAL), kidney injury molecule-1 (KIM-1), transforming growth factor beta-1 (TGF-beta 1), retinolbinding protein (RBP), and microalbuminuria (mu ALB), was analyzed in a cohort of 37 infants with congenital UTO, divided into three subgroups, 14 cases with grade III unilateral hydro (uretero)nephrosis, 13 cases with grade III bilateral hydro (uretero)nephrosis, and 10 cases with low urinary tract obstruction (LUTO), compared with 24 healthy infants matched by gestational age and birth weight. Serum and urine samples were stored at -70 degrees C and thereafter analyzed by quantitative enzymatic immunoassay. Results Compared with the control group (Figure), all renal biomarker values were significantly increased in patients (P <= 0.02). In the unilateral hydronephrosis and LUTO group, RBP (P <= 0.043), NGAL (P <= 0.043), KIM-1 (P <= 0.03), and TGF-beta 1 (P <= 0.034) values dropped significantly after surgery. Neutrophil gelatinase-associated lipocalin alone and in combination with urine and serum CyC demonstrated the best performance in determining the need for surgery (area under the curve, 0.801 and 0.881, respectively). Biomarker profile analysis was suggestive of surgical intervention in 55.4% (7/13) of non-operated cases, and most of the biomarker values were above the cutoff levels within at least 3 months before the clinically based surgical decision in 58% (14/24) of all operated patients. Discussion To the best of the authors' knowledge, this is the first study to present the clinical use of selected group of serum and urinary biomarkers in the setting of UTO to distinguish between patients who would benefit from surgery intervention. The most promising results were obtained using NGAL, RBP, TGF-beta 1, and KIM-1, especially in the unilateral hydro(uretero)nephrosis and LUTO subgroups when compared with the control group. Conclusions Urine biomarkers, alone and in combination, demonstrated high potential as a non-invasive diagnostic tool for identifying infants who may benefit from earlier surgical intervention. [GRAPHICS] .
- Pyeloplasty vs. nephrectomy for ureteropelvic junction obstruction in poorly functioning kidneys (differential renal function < 20%): a multicentric study(2019) GNECH, M.; BERRETTINI, A.; I, R. Lopes; MOSCARDI, P.; ESPOSITO, C.; ZUCCHETTA, P.; DENES, F. T.; MANZONI, G.; BRAGA, L. H.; CASTAGNETTI, M.Introduction Management of poorly functioning kidneys with ureteropelvic junction obstruction (UPJO) is controversial, with some recommending direct nephrectomy and others direct pyeloplasty, and others temporary diversion. This study aimed to determine whether pyeloplasty is associated with higher complication rate than nephrectomy under these circumstances and whether it allows for functional recovery. Methods A retrospective review of 77 patients undergoing surgery for UPJO associated with a differential renal function (DRF) < 20% at 4 centres between January 2000 and December 2015 was conducted. Short- and long-term complications between pyeloplasties (n = 47) and nephrectomies (n = 16) and the changes in the DRF after pyeloplasty were compared. Results Patients undergoing nephrectomy had significantly lower median pre-operative DRF (p < 0.001) and were significantly more likely to undergo a minimally invasive approach (p = 0.002) than those undergoing pyeloplasty. No postoperative variable was statistically different between groups. After a mean follow-up of 63 (10-248) months, no statistically significant difference was found in intra-operative, early, late, and overall complications between pyeloplasty and nephrectomy. Pyeloplasty failed in 3% (2/62) of cases. Of the patients undergoing successful pyeloplasty, 36 had a pre-operative and a postoperative renogram, and functional recovery >5% was observed in '13 (36%), whereas the DRF remained unchanged in 16 (45%). Only postnatal diagnosis was associated with a significantly higher chance of functional recovery (odds ratio [OR] = 4.13, p = 0.047). Discussion Nephrectomy was more commonly performed using a minimally invasive approach and required less-intense follow-up than pyeloplasty. Moreover, complications after pyeloplasty, although occasional, required additional surgery which was never required after nephrectomy. Moreover, it should be considered that conservative treatment might be a third option in some of these patients. Conclusions In the study patients, pyeloplasty was not associated with significantly higher morbidity than nephrectomy. Need for deferred nephrectomy seems exceptional in decompressed kidneys even though renal function remains poor. Of the pyeloplasty cases not requiring additional surgery, one-third showed an improvement in DRF and a postnatal diagnosis was the only predictive factor for renal functional recovery.
- Urethral duplication type influences on the complications rate and number of surgical procedures(2017) LOPES, Roberto Iglesias; GIRON, Amilcar Martins; MELLO, Marcos Figueiredo; BARBOSA NETO, Cristovao Machado; SANTOS, Joana dos; MOSCARDI, Paulo Renato Marcelo; SROUGI, Victor; DENES, Francisco Tibor; SROUGI, MiguelIntroduction: 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 1988-02015. 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 (3-0136 months). Mean follow-up was 7.7 +/- 3.4 years (3y8m-014y2m). 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.
- Management of functioning pediatric adrenal tumors(2021) LOPES, Roberto Iglesias; SUARTZ, Caio Vinicius; PEDRENHO NETO, Rubens; BERJEAUT, Ricardo Haidar; MENDONCA, Berenice; ALMEIDA, Madson Q.; FRAGOSO, Maria Candida Villares; DENES, Francisco TiborAim: The aim of this study is to present our experience in the management of hormonally active adrenal tumors in children.& nbsp; Material and methods: We did a retrospective chart review of all children with hormonally active adrenal tumors evaluated at the endocrinology clinic and operated at our institution between 1983 and 2019.& nbsp; Results: There were 75 patients included in the study, 58 with adrenocortical tumors (ACTs) and 17 with pheochromocytomas (PCCs). Within the group of patients with ACTs, there were 41 females and 17 males. The mean age was 58.3 (SD: 87.9; range: 9 & ndash;211) months. The clinical manifestation of the tumor's hormonal activity was virilization in 37 cases, Cushing syndrome in 5, and mixed in 16. A positive family history was present in 11 patients (18.9%). The mean tumor size was 48.2 (SD: 22.4; range: 7 & ndash;120) mm. The pathological diagnosis was adenoma in 42 cases, carcinoma in 15 cases, and macronodular hyperplasia in 1. Median follow-up was 192 (range: 50 & ndash;290) months. Tumor recurrence occurred in 6 patients (10.3%), and there were three disease-related deaths (5%). Within the group of patients with PCCs, there were 11 males and 6 females. The mean age was 146.7 (SD: 71.2; range: 60 & ndash;216) months. A positive family history was present in 7 patients (41.2%). The mean tumor size was 36.6 (SD: 16.7; range: 7 & ndash;120) mm. The pheochromocytoma was classified as benign in 15 cases and as malignant in 2. During a median follow-up of 180 (range: 127 & ndash;300) months, recurrence was observed in 6 cases (35.3%) and disease-related death in 1 case (5.9%).& nbsp; Conclusions: Proper diagnosis and management at our referral center were associated with a high cure rate, even in cases of malignant tumors. Familial surveillance is highly recommended.& nbsp; Level of evidence: Level IV.& nbsp; (c) 2020 Elsevier Inc. All rights reserved.
- 27 years of experience with the comprehensive surgical treatment of prune belly syndrome(2015) LOPES, R. I.; TAVARES, A.; SROUGI, M.; DENES, F. T.Introduction Prune belly syndrome (PBS) presents with three main features: abdominal wall flaccidity, urological abnormalities and cryptorchidism. As a result, urologists must consider the eventual repair of the abdominal wall flaccidity and urinary tract abnormalities, and the mandatory correction of cryptorchidism, as well as decide whether to perform the procedures in a single comprehensive approach or in multiple steps. Objectives To report experiences with comprehensive surgical management of prune belly syndrome. Material and methods From 1987 to 2014, 46 children with PBS were submitted for comprehensive surgical treatment. According to individual needs, treatment aimed to correct the abdominal flaccidity, reconstruct the urinary tract, and perform bilateral orchiopexy and circumcision, which were performed in one procedure. Urinary tract reconstruction was indicated whenever pyelo-ureteral dilatation with evidence of significant stasis and/or vesicoureteral reflux was associated with recurrent urinary tract infections (UTI). Treatment for this cohort included: 44 abdominoplasties, 40 upper urinary tract reconstructions, 44 cystoplasties associated with three appendico-vesicostomies, 46 bilateral orchiopexies and 36 circumcisions. The median age at surgery was 16 months and children were followed for a median of 143 months. Results Abdominal appearance and tonus were improved in 90% of the children after the primary surgery and 100% after reoperation. Upper urinary tract reconstruction was performed in most children and long-term follow-up showed functional stabilization of the urinary tract in about 90% of the children, with progression to renal failure in 10%. Lower urinary tract reconstruction was performed in most children (95.6%); on late follow-up, continence was observed in 81% of them, while incontinence was present in 19% and usually associated with polyuria. Adequate bladder emptying was possible in most boys (82.6%), while the remaining required clean intermittent catheterization. Pre-operative UTI was present in 89.1% and urinary sepsis in 15.2%. Postoperatively, the incidence of laboratorial UTI was significantly reduced to 39.1%, while urinary sepsis was absent. Bilateral orchiopexy was performed in all children, with 85% of the testes becoming normal in size and well located in the scrotum. Conclusions Comprehensive surgical treatment is feasible and has good long-term results. A considerable incidence of reoperations due to complications or progression of the disease was observed. The long-term results for reno-ureteral anatomy and function, bladder function, infection, testicular size and location, as well as abdominal aspect and tonus, show that comprehensive surgery is an adequate method for managing children with PBS.
- Gonadal Function and Reproductive System Anatomy in Postpubertal Prune-Belly Syndrome Patients(2020) LOPES, Roberto Iglesias; TAVARES, Alessandro; DENES, Francisco Tibor; COCUZZA, MarcelloOBJECTIVE To gain insight into the causes of infertility in Prune Belly Syndrome (PBS) by evaluating reproductive system anatomy and gonadal function in a cohort of postpubertal PBS patients. METHODS We contacted all PBS patients 14 years old or older treated and followed at our institution. Age at orchiopexy, type of orchiopexy (with or without ligation of gonadal vessels), testicular volumes and positions were evaluated. Pelvic magnetic resonance imaging (to assess prostate size, seminal vesicles, and vas) and hormonal profile were ordered. Sperm analysis and analysis of urine after masturbation were performed after informed consent. RESULTS Fifteen patients were included in this study. Mean age was 19.2 years. Mean age at orchiopexy was 18 months. Fourteen patients (93.3%) had normal and orthotopic testes. Mean testicular volume was 6.9 cc. Eight patients collected semen, 5 of them (62.5%) had spermatozoa in the specimen and motile sperm was found in 4 (50%). Mean hormone levels were LH: 5.3 mg/dL, FSH: 6.9 mg/dL, testosterone 531 mg/dL. Magnetic resonance imaging revealed hypoplastic prostates in 66.6% and unilateral seminal vesicle absence in 66.6%. No vasal abnormality was noted. CONCLUSION Patients with PBS may have normal sexual hormonal levels. Motile spermatozoa were found in half of the patients. Our study highlights a high prevalence of prostate and seminal vesicle abnormalities that may represent an important cause for their infertility. (C) 2020 Elsevier Inc.
- Videolaparoscopic radical nephrectomy after chemotherapy in the treatment of Wilms' tumor: Long-term results of a pioneer group(2017) DUARTE, Ricardo Jordao; CRISTOFANI, Lilian Maria; ODONE FILHO, Vicente; SROUGI, Miguel; DENES, Francisco TiborIntroduction A high cure rate for Wilms' tumor has been achieved using a multidisciplinary approach. The natural step forward is to offer the benefits of a minimally invasive technique for surgery, which is an obligatory part of treatment. Nevertheless, some authors resist using videolaparoscopic radical nephrectomy (VRN) because of concerns about reducing the cure index. Methods The present study included children with unilateral Wilms' tumor treated from December 2003 to December 2015 with neoadjuvant chemotherapy followed by VRN. Patients were selected based on the size of their tumors compared with the contralateral kidney, and on their stature. Results VRN was performed in 24 patients of age range 10-93 months, with an average of 38.04 +/- 23.37 months. The tumoral kidney's largest diameter after chemotherapy averaged 10% of a patient's height. There was no tumor rupture or spillage and no patient presented intra or immediate postoperative complications, except for prolonged ileum in two patients. One patient required intraoperative transfusion because of preoperative anemia. Another developed a late herniation in the umbilical port that required surgical correction. After an average of 6.65 years of follow-up, two patients presented relapse: one with a stage IV disease had relapse in the lung and another with a stage III, involving the liver, had local relapse because of an unwanted delay in the adjuvant treatment. Conclusion VRN can be considered a feasible alternative to open surgery in selected cases of children with Wilms' tumor. The present experience shows that besides the benefits of minimally invasive procedures and better cosmetic results, there is no evidence of increased tumor rupture or spillage, peritoneal or port site metastasis, and the long-term oncological results are the same as open procedures.
- Robotic abdominoplasty for abdominal wall lateral bulging repair in an adult prune belly syndrome patient: a novel approach(2021) I, R. Lopes; ABDALLA, R. Z.; DENES, F. T.
- Serum and Urinary Values of CA 19-9 and TGF beta 1 in a Rat Model of Partial or Complete Ureteral Obstruction(2015) LOPES, Roberto Iglesias; DENES, Francisco Tibor; BARTOLAMEI, Matheus Gesualdo; REIS, Sabrina; SANCHES, Talita Rojas; LEITE, Katia Ramos; SROUGI, Miguel; SEGURO, Antonio CarlosIntroduction Abnormal levels of serum and urinary markers occur in the presence of renal damage associated to obstructive uropathy. Urinary and serum transforming growth factor beta 1 (TGF beta 1) and carbohydrate antigen (CA 19-9) have not yet been evaluated in an experimental model of obstructive uropathy. Material and Methods Rats were divided into seven groups: reference, sham operation, unilateral nephrectomy, complete unilateral ureteral obstruction, partial unilateral ureteral obstruction, partial bilateral ureteral obstruction, and unilateral nephrectomy with contralateral partial ureteral obstruction. Kidney and ureter morphometry, TGF beta 1 and CA 19-9 serum and urinary concentrations and CA 19-9 renal tissue expression were analyzed. Correlation of these markers to complete, partial obstruction, or unobstructed groups was performed. Results Pathological findings correlated positively with the degree of ureteral obstruction, but negatively with urinary CA 19-9 levels. Marked underexpression of CA 19-9 was observed in kidneys with complete ureteral obstruction. No statistically significant differences were found for urinary and serum TGF beta 1 and also for serum CA 19-9. Conclusion Urinary CA 19-9 correlated negatively with ureteral obstruction grade. Immunohistochemistry depicted CA 19-9 expression on epithelial tubular cells cytoplasm, suggesting renal origin. Serum and urinary TGF beta 1 did not show alterations in response to severity and length of urinary obstruction, which might be associated with less intense renal remodeling.