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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- 46,XY DSD due to 17 beta-HSD3 Deficiency and 5 alpha-Reductase Type 2 Deficiency(2011) INACIO, Marlene; SIRCILI, Maria Helena P.; BRITO, Vinicius N.; DOMENICE, Sorahia; OLIVEIRA-JUNIOR, Ari Alves; ARNHOLD, Ivo J. P.; TIBOR, Francisco D.; COSTA, Elaine M. F.; MENDONCA, Berenice B.
- 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.
- Elevated plasma miR-210 expression is associated with atypical genitalia in patients with 46,XY differences in sex development(2022) ELIAS, Felipe Martins; NISHI, Mirian Yumi; SIRCILI, Maria Helena Palma; BASTISTA, Rafael Loch; GOMES, Nathalia Lisboa; FERRARI, Maria Tereza Martins; COSTA, Elaine Maria Frade; DENES, Francisco Tibor; MENDONCA, Berenice Bilharinho; DOMENICE, SorahiaBackground: Differences of sex development (DSD) is a term used for conditions in which the chromosomal, gonadal or phenotypical sex is atypical. 46,XY DSD patients frequently present undervirilized external genitalia. The expression of different miRNAs in many organs of the male genital system has been reported, and these miRNAs have been associated with testicular function and its disorders, but no description has been related to DSD conditions. This study aimed to evaluate the plasma expression of miR-210 in 46,XY DSD patients who presented atypical genitalia at birth. Methods: Eighteen 46,XY DSD patients who presented atypical genitalia (undescended testis and/or hypospadias, bifid scrotum or micropenis) at birth and 36 male control individuals were selected. Plasma levels of miR-210 and reference miR-23a were measured using RT-qPCR and the data were analysed by the 2(-Delta Ct) method. Results: MiR-210 plasma levels were significantly higher in 46,XY DSD patients with atypical genitalia than in male control subjects (p = 0.0024). A positive association between miR-210 levels and the presence of cryptorchidism and hypospadias (p = 0.0146 and p = 0.0223) was found in these patients. Significantly higher levels of miR-210 were observed in patients with 46,XY DSD and cryptorchidism than in control subjects (p = 0.0118). These results are in agreement with previous literature reports, in which increased levels of miR-210 expression were observed in human testicular tissue from adult males with undescended testes in comparison with samples of descended testes. Conclusion: Our study showed a positive association between the presence of atypical genitalia and plasma levels of miR-210 expression in the group of patients with 46,XY DSD of unknown aetiology studied. These findings contribute to reveal a new perspective on the role of miRNAs in the development of male external genitalia and the broad spectrum of phenotypes presented by patients with 46,XY DSD.
- Evaluating TIMP-2 and IGFBP-7 as a predictive tool for kidney injury in ureteropelvic junction obstruction(2022) MELLO, Marcos Figueiredo; BESSA JUNIOR, Jose de; REIS, Sabrina T.; KONDO, Enzo Yagi; YU, Luis; DENES, Francisco Tibor; LOPES, Roberto IglesiasA major challenge in the management of ureteropelvic junction obstruction (UPJO) is the selection of patients who would benefit from surgical treatment. Tissue inhibitor metalloproteinase-2 (TIMP-2) and insulin-like growth factor-binding protein 7 (IGFBP7) indicate renal cell stress and are associated with cell cycle arrest. The [TIMP-2] [IGFBP7] ratio (Nephrocheck (R)) has been recently applied in patients in intensive care units patients to predict the development of acute kidney injury. In this study, we evaluated the performance of these biomarkers performance to distinguishing obstructive hydronephrosis (HN) from non-obstructive HN. Materials and Methods: Consecutive patients with UPJO were enrolled in this study. Urinary [TIMP-2] [IGFBP7] and clinical characteristics (hydronephrosis grade, differential renal function, and drainage half-time) were measured in the following groups: 26 children with obstructive HN at initial diagnosis (group IA) and after six months of dismembered pyeloplasty (group 1B); 22 children with non-obstructive HN (group 2), and 26 children without any urinary tract condition, as the control group (group 3). Results: Comparing the initial samples, [TIMP-2] [IGFBP7] had higher levels in the HN groups and lower levels in the control group; however, no difference was observed between the HN groups (obstructive vs. non-obstructive). After six months of followup, patients who underwent dismembered pyeloplasty showed stability in the urinary concentration of [TIMP-2] [IGFBP7]. All patients with [TIMP-2] [IGFBP7] higher than 1.0 (ng/mL)(2)/1000 had diffuse cortical atrophy on ultrasonography. Conclusions: We showed that urinary levels of urinary [TIMP-2] [IGFBP7] are higher in children with HN than controls. Nephrocheck (R) is not reliable in predicting the need for surgical intervention for pediatric patients with UPJO.
- Urinary extracellular matrix proteins as predictors of the severity of ureteropelvic junction obstruction in children(2021) MELLO, Marcos Figueiredo; REIS, Sabrina Thalita dos; KONDO, Enzo Yagi; BESSA JUNIOR, Jose de; DENES, Francisco Tibor; LOPES, Roberto IglesiasIntroduction Ureteropelvic junction obstruction (UPJO) particu-larly represents a challenge in regard to manage-ment, as not all hydronephrosis (HN) represent a kidney-damaging state. Urinary biomarkers have been proposed as noninvasive tools. Extracellular matrix (ECM) proteins are associated with tissue fibrosis in the setting of UPJO and is poorly explored. Objective To investigate whether urinary ECM proteins are useful to discriminate the severity of urinary obstruction on unilateral UPJO. Study design Children with unilateral UPJO were prospective enrolled. Urinary (u) matrix metalloproteinases (MMP-1,-2,-9 and TIMP-1,-2) as well as clinical characteristics were measured in the following groups: 26 children with obstructive HN at initial diagnosis and after six months of dismembered pyeloplasty; 22 children with non-obstructive HN at diagnosis and after six months of observation; 26 children without any urinary tract condition, as the control group. Results were assessed statistically using for homogenous groups, a one-way analysis of variances (ANOVA) and for nonparametric groups, Mann-Whitney test or Kruskal-Wallis test was per -formed. ROC curves were performed. Results Baseline samples demonstrated a higher concentra-tion of uMMP-1/Cr, uMMP-2/Cr, u-TIMP-1/Cr and u-TIMP-2/Cr in obstructive HN group; uMMP-9/Cr levels were higher in non-obstructive HN group and all studied biomarkers had lower concentrations for the control group. On follow-up, for the obstructive HN group, urinary concentration of uTIMP-1/Cr and uTIMP-2/Cr decreased, and uMMP-1/Cr, uMMP-2/Cr and uMMP-9/Cr increased when comparing preop-erative to postoperative values. In the non-obstructive HN group, all proteins analyzed were stable after six months of observation. ROC curves analysis showed a promising diagnostic profile for the detection of obstructive HN for uTIMP-1/Cr (area under the curve-AUC-; of 0.692), uTIMP-2/Cr (AUC of 0.678) and for uMMP-2/Cr (AUC of 0.655). Discussion The severity of kidney obstruction could correlate with the urinary ECM proteins concentration in this study. This is concordant with prior studies demon-strating that a disruption of the balance of accu-mulation/degradation of the ECM proteins occur on obstructive uropathy. Limitations of our study include the older age of our patients and that these markers had no influence at all on the surgical decision. Conclusion We demonstrate that obstructive HN have signifi-cantly higher uMMP-2, uTIMP-1 and uTIMP-2 con-centrations. Particularly, uTIMP-2 levels were correlated to severity of obstruction and therefore, it might be a useful urinary biomarker to correctly allocate children with HN between surgical man-agement vs follow-up. After pyeloplasty, uTIMP-1 and uTIMP-2 presented a progressive decrease postoperatively, which is also highly desirable for urinary markers.
- Laparoscopic ureterocalicostomy for complicated upper urinary tract obstruction: mid-term follow-up(2014) ARAP, Marco Antonio; ANDRADE, Hiury; TORRICELLI, Fabio Cesar Miranda; DENES, Francisco Tibor; MITRE, Anuar Ibrahim; DUARTE, Ricardo Jordao; SROUGI, MiguelTo report on the largest series of laparoscopic ureterocalicostomies done for complicated upper urinary obstruction. We retrospectively reviewed the data from 6 transperitoneal laparoscopic ureterocalicostomies performed in our institution from January 2008 to January 2012. Symptomatic complicated upper urinary obstruction was the main reason for all the procedures. The recorded data included age, gender, clinical presentation, duration of symptoms, laterality, mean operative time, hospital stay, complications and clinical and functional outcomes. The median patient age was 20.1 (2-44) years, and all patients were females. Patients underwent laparoscopic ureterocalicostomy due to previous failed procedures (3 patients), anatomic abnormalities (2 patients) and a severe upper ureteral stenosis (1 patient). The median operative time was 215 (180-270) min. There were no major complications. There were no conversions to open surgery. In a median follow-up of 30 (8-56) months, all patients presented with clinical and radiological improvement with no signs of obstruction. In all cases, the postoperative renal scintigraphy revealed a T1/2 lower than 10 min. Laparoscopic ureterocalicostomy is feasible and associated with high success rate in well-selected cases with complicated upper urinary obstructions.
- Transperitoneal laparoscopic pyeloplasty in children: does upper urinary tract anomalies affect surgical outcomes?(2018) BRUNHARA, Joao Arthur; MOSCARDI, Paulo Renato Marcelo; MELLO, Marcos Figueiredo; ANDRADE, Hiury Silva; CARVALHO, Paulo Afonso de; CEZARINO, Bruno Nicolino; DENES, Francisco Tibor; LOPES, Roberto IglesiasObjective: To assess the feasibility and outcomes of laparoscopic pyeloplasty in children with complex ureteropelvic junction obstruction (UPJO) and compare to children with iso-lated UPJO without associated urinary tract abnormalities. Material and Methods: Medical records of 82 consecutive children submitted to trans-peritoneal laparoscopic pyeloplasty in a 12-year period were reviewed. Eleven cases were con-sidered complex, consisting of atypical anatomy including horseshoe kidneys in 6 patients, pelvic kidneys in 3 patients, and a duplex collecting system in 2 patients. Patients were di-vided into 2 groups: normal anatomy (group 1) and complex cases (group 2). Demographics, perioperative data, outcomes and complications were recorded and analyzed. Results: Mean age was 8.9 years (0.5-17.9) for group 1 and 5.9 years (0.5-17.2) for group 2, p=0.08. The median operative time was 200 minutes (180-230) for group 1 and 203 minutes (120-300) for group 2, p=0.15. Major complications (Clavien =3) were 4 (5.6%) in group 1 and 1 (6.3%) in group 2, p=0.52. No deaths or early postoperative complications such as: urinoma or urinary leakage or bleeding, occurred. The success rate for radiologic improvement and flank pain improvement was comparable between the two groups. Re-garding hydronephrosis, significant improvement was present in 62 patients (93.4%) of group 1 and 10 cases (90.9%) of group 2, p=0.99. The median hospital stay was 4 days (IQR 3-4) for group 1 and 4.8 days (IQR 3-6) for group 2, p=0.27. Conclusions: Transperitoneal laparoscopic pyeloplasty is feasible and effective for the management of UPJO associated with renal or urinary tract anomalies.
- Surgical Treatment after Failed Primary Correction of Urogenital Sinus in Female Patients with Virilizing Congenital Adrenal Hyperplasia: Are Good Results Possible?(2016) SIRCILI, Maria Helena Palma; BACHEGA, Tania Sartori Sanchez; MADUREIRA, Guiomar; GOMES, Larissa; MENDONCA, Berenice Bilharinho; DENES, Francisco TiborPurpose: Genital reconstruction in female patients with virilizing congenital adrenal hyperplasia (CAH) is very challenging. Our aim was to evaluate the techniques employed to treat complications after failure of primary urogenital sinus (UGS) surgery, as well as the result of these reoperations. Patients and methods: Twenty girls with virilizing CAH who were previously submitted to genitoplasty in our service and elsewhere had recurrent UGS stenosis and vaginal introitus stenosis that required surgical treatment. The main symptoms were recurrent urinary tract infection (UTI) in nine, dyspareunia in six, and hematocolpos in three (two associated with sepsis). The anatomical findings were the persistence of UGS with stenosis in 17 patients and vaginal introitus stenosis in 3. The mean age at procedure was 15.2 years, averaging 13.1 years after the first surgery. The surgical techniques employed were isolated perineal flap in 17 patients and perineal flap with partial mobilization of UGS in 3. The mean follow-up after the procedure was 4.8 years (varying from 1 to 17 years). Results: Vaginal dilations were performed after surgery in 15 patients. Good functional and anatomical results were obtained in 15 patients, with vaginal introitus amenable to dilators of 3.0 cm in diameter. Five patients with high vaginal insertion had recurrent vaginal stenosis and required a surgical revision. No patients presented menstrual obstruction or UTI after surgery. Eight of the 15 adult patients are sexually active. Conclusion: The reoperation to treat failed primary UGS treatment using Y-V flap and partial mobilization techniques associated with vaginal dilations, promoted good anatomical, and functional results with low morbidity in 75% of the patients.
- Malignant paraganglioma in children treated with embolization prior to surgical excision(2016) MIRANDA, Eduardo de Paula; LOPES, Roberto Iglesias; PADOVANI, Guilherme Philomeno; MOSCARDI, Paulo Renato Marcelo; NISHIMURA, Fernanda Gardini Maciel; MENDONCA, Berenice Bilharinho de; CARNEVALE, Francisco Cesar; CRISTOFANI, Lilian Maria; DUARTE, Ricardo Jordao; SROUGI, Miguel; DENES, Francisco TiborBackground: Paragangliomas (PGL) are rare tumors derived from neural crest cells, whose origins may vary along the chain of the sympathetic nervous system. Such tumors are often characterized by secretion of catecholamines, but sometimes they are biochemically inactive, which makes diagnosis often challenging. Malignant paraganglioma is defined by the presence of this tumor at sites where chromaffin cells are usually not found or by local invasion of the primary tumor. Recurrence, either regional or metastatic, usually occurs within 5 years of the initial complete resection but long-term recurrence is also described. Malignancy is often linked to a SDHB mutation. Preoperative embolization has been applied in the surgical management of PGLs with the objective to decrease intra-operative blood loss and surgery length without complications. Case Presentation: We report two cases of patients with abdominal or pelvic malignant PGLs who have been treated surgically at our center after preoperative embolization. Surgery was a very challenging procedure with multiple surgical teams involved and embolization did not prevent major blood loss and intraoperative complications. Patients required adjuvant treatment with either chemotherapy or radiotherapy. Conclusions: Many studies in the adult population have established recommendations for the diagnosis and therapeutic management of PGL, but few studies concern the pediatric population. Because malignant PGL is more important in the pediatric population, screening and early diagnosis of PGL is advisable in children with genetic predisposing. Surgical resection is the mainstay of treatment, but a multimodal approach is often required due to the complexity of cases. The role of preoperative embolization is not established and in our experience it has provided little benefit and major complications.
- Laparoscopic ureteropyeloanastomosis in the treatment of duplex system(2012) HISANO, Marcelo; DENES, Francisco T.; BRITO, Artur H.; LUCON, Marcos; MACHADO, Marcos G.; BRUSCHINI, Homero; SROUGI, MiguelPurpose: Duplex system is one of the most common anomalies of upper urinary tract. Anatomical and clinical presentation determine its treatment. Usually, the upper moiety has a poor function and requires resection, but when it is not significantly impaired, preservation is recommended. Laparoscopic reconstruction with upper pole preservation is presented as an alternative treatment. Materials and Methods: Four female patients with duplex system, one presenting with recurrent urinary tract infection and the others with urinary incontinence associated to infrasphincteric ectopic ureter, were treated. Surgical procedure envolved a laparoscopic ureteropyeloanastomosis of the upper pole ureter to the pelvis of the lower moiety, with prior insertion of a double J stent. Results: Surgical time varied from 120 to 150 minutes, with minimal blood loss in all cases. Follow-up varied from 15 to 30 months, with resolution of the clinical symptoms and preservation of the upper moiety function. Conclusion: Laparoscopic ureteropyeloanatomosis is a feasible and safe minimally invasive option in the treatment of duplex system.