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Introduction: Since the Management of Myelomeningocele Study (MOMS) publication in 2011 we have designed a prospective protocol for surveillance of neurogenic bladder according to the Leal da Cruz categorization system (J Urol, 2015) that guides us on treatment. Our institution was the precursor of in-utero myelomeningocele (MMC) in Latin America, so our database was biased mostly for patients that underwent fetal surgery for MMC closure. We have demonstrated that in-utero MMC closure does not improve bladder function in opposition to the data from the urological branch of the MOMS study (10), but our control group was based on a historical cohort, before the onset of in-utero MMC repair in our division (15) Since 2018, we have identified an increasing number of referrals of postnatal operated MMC patients to our group just for urological follow up. We decided then to start this prospective protocol for all neurogenic patients and provide a contemporary database to record differences in early bladder function, presence of hydronephrosis and vesicoureteral reflux, treatment, initial outcome and indication of surgery among three mains groups (in-utero MMC repair, post-natal repair and miscellaneous other cases of neurogenic bladder). We want to present preliminary data of this cohort in the period of time 2018 to 2023 (5 years). There was not an exclusion criteria, all patients with neuropathic bladder were included in this study., Materials and Methods: We evaluated our database of all neurogenic bladder (NB) patients aged <1 year who started urological treatment in our institution from 2018. We evaluated diagnosis, age at first visit, clinical data, prevalence of hydronephrosis and (vesicoureteral reflux) VUR, bladder pattern according to the Leal da Cruz categorization system (1), treatment, time of follow-up, number of clinical visits and (urodynamic evaluation) UE performed, final bladder status and surgeries performed., Results: We identified 43 were aged <1 year with a mean age of 4.5 months (median 3.5) at first urological appointment. Diagnosis was myelomeningocele in 33 patients and miscellaneous in 10. From the MMC group, 24 were operated in-utero and 9 post-natal. The initial bladder pattern in the whole group showed 23 (53.5%) high risk, 11 normal (25.6%), 5 underactive bladder (11.6%) and 4 incontinent (9.3%). Mean follow-up was 24 months, mean age at last UE (cases with minimum of 2): 37 months, mean UE per patient: 2. At present, 28 patients perform clean intermittent catheterization (CIC), 23 with anticholinergics and 15 are only under surveillance. VUR was seen in 11/43 cases: 25.6%. Urological surgery has been performed in 4 patients: bladder augmentation in 3 and vesicostomy in 1. Bladder categorization for high-risk and normal patterns were respectively 62.5% and 25% for in utero and 44.4% and 22.2% for postnatal repair and detailed statistical analysis did not present statistical significance of in utero and postnatal groups., Conclusion: Our study can conclude in a contemporary prospective study the findings of elevated incidence of high-risk patterns irrespectively of in-utero or post-natal repair (62.5% and 44.4%). We acknowledge that even though this is not new information and besides the still limited follow up, this cohort is one of the very few that follow and compare in one single institution with comparable UE for in-utero and post-natal MMC repair population, having also a miscellaneous group of NB as a pictorial report of also a similar initial distribution of bladder patterns. We plan to report in the future in a larger cohort the continuation of this study., (Copyright © 2024. Published by Elsevier Ltd.)

Introduction: The Macedo ileal catheterizable channel was published in 2000 and consists of an enterocystoplasty with a catheterizable channel that precludes the need of the appendix for the efferent channel. After 25 years of experience with this technique, we decided to review our experience in a select subgroup of cases performed and followed exclusively by the author in a non-teaching hospital facility after the latest modifications of the procedure., Materials and Methods: Since 2008, we have refined our technique with the following modifications: small skin transverse incision instead of longitudinal one, with a semicircular flap for further stoma creation in the midline and importantly the scissors maneuver. This maneuver consists of crossing two 2 cm rectus abdominis muscle flaps in the midline to create a neosphincter over the catheterizable channel. Follow-up was defined as the interval between the date of surgery and last visit to the clinic. We defined stoma continence if the dry interval between catheterization was 4hs. Early and late complications were reported as well as the reintervention rate. Additional procedures in association with bladder augmentation were also appointed., Results: We have treated 49 patients. Indications were spinal dysraphism (71.4%), mainly myelomeningocele (65.3%), and others (PUV, exstrophy, anorectal anomalies). Urodynamic evaluation showed bladder pressure of high risk for upper urinary tract involvement (66%), urinary incontinence (24.5%), conversion of incontinent urinary diversion (3.8%), one exstrophy patient not considered (1.9%). Mean age at surgery was 88 months (7.3 years), 21 patients had additional surgeries in addition to Macedo ileal catheterizable channel: Macedo-Malone LACE procedure in 21 patients and bladder neck surgery to improve continence in 5 patients. Urinary stoma continence was 93.9% (46/49) after first surgery, one patient had a serous line valve revised, two patients still leak after 2 h and await revision. Overall enterocystoplasty complications rate was 12.24% and consisted of urinary leakage in 3 cases and channel/stoma stricture in 3 cases. All patients treated for sphincteric deficiency associated with bladder reconstruction are continent per urethra. Urinary stoma revision for stricture was done in 2 cases and consisted on suprafascial approach and reanastomosis, one patient resolved with dilatation of the channel to the stoma. Mean follow up is 100 months (8.3 years)., Conclusion: We confirmed in a long term follow-up based on face-to-face visits with 8.3 years mean follow-up that the Macedo procedure associated with the scissors maneuver is associated with 93.9% continence of the stoma. Overall complications rate was 12.24%. The cosmetic aspect with a small transverse incision and a midline stoma is another strength of the technique., (Copyright © 2024 Journal of Pediatric Urology Company. Published by Elsevier Ltd. All rights reserved.)

Introduction: In-utero myelomeningocele repair is the gold standard treatment after the publication of the MOMS trial. We have performed a retrospective analysis from our prospective in-utero myelomeningocele closure database (started in 2011), and selected only patients with the incontinent bladder pattern according to the Leal da Cruz categorization (Leal da Cruz, et al. J Urol 2015) to review mid-term clinical outcomes., Material and Methods: We identified 30 patients with leaking pressure under 40 cmH20 (incontinent pattern) at first urodynamic evaluation (UE) from the whole cohort of 129 patients who underwent in-utero myelomeningocele closure. We selected patients with a minimum active follow-up of 48 weeks (4 years) to provide mid-term data. Patients were followed according to the same protocol with the proposal of yearly sonogram and UE. All clinical and radiological data were reviewed., Results: We found 11 patients, with a mean age of 10.2 years old, median age at diagnosis of 19 weeks, surgery performed at 25.6 weeks and birth at 33.2 weeks. The mean follow-up was 81.73 months (6.81 years). Mean age at first urological evaluation was 5 months, and UE was 5.6 months. Febrile UTI incidence in the whole observation period was 27.3%. The average initial DLPP was 30 cmH2O. 71.4% of the patients had bladder capacity less than 50% of the expected age. Bladder compliance could not be determined in 63.7% of cases due to leakage. A total of 5.7 urodynamic studies per patient were performed. Surgery was recommended for 8 patients and done in 4 (36.3%). Surgery consisted of Macedo catheterizable reservoir and Macedo-Malone ACE, associated with urethral sling (2 patients) and bladder neck closure (2). It took an average of 5 UE before the final surgical decision was confirmed. Last urodynamic study showed persistent leakage and low DLPP in 3 patients, normal bladder pressure in 2 (under CIC and anticholinergics), and 1 patient changed his bladder pattern into a high risk group. All operated patients are fully continent (urinary >4hs) and fecal., Conclusion: Despite initially presenting a low risk for the most patients, we found surgery in 36.3% (4/11) and if we considered all cases with surgery indication proposed to treat urinary incontinence it would be even higher (72.7%)., (Copyright © 2024 Journal of Pediatric Urology Company. Published by Elsevier Ltd. All rights reserved.)

Introduction: After 5 years experience with the GUD (glandular urethral disassembly) technique for distal hypospadias, we present the GUDplay technique, incorporating Thiersch-Duplay tubularization of the plate till the coronal area, disassembling the glans aggressively and refurbishing the glans., Methods: We defined the urethral plate and designed an inverted Y incision to open the glans in two wings. The glans was entirely detached from the corpora to gain a great mobility that allowed minor cranial mobilization of the urethra and caudal rotation of the wings. In sequence, there are well-known steps: Duplay urethroplasty, spongioblasts and a Dartos flap to cover the neourethra. The glans was connected to the urethra by 6.0 PDS sutures except in the ventral meatus and the glans wings are joined in the midline., Results: The 5-year-old patient had midshaft hypospadias without previous surgery. The catheter was removed after a week and the healing appears to be good., Discussion: We combined principles of total glans deconstruction in association to Duplay tubularization and then lifted it up to the tip of the glans divided in two wide and mobile wings. We have treated a small series of 6 cases without complications and mean follow-up of 6.2 months., (Copyright © 2024 Journal of Pediatric Urology Company. Published by Elsevier Ltd. All rights reserved.)

Spinal muscular atrophy (SMA) is a neurodegenerative disorder caused by mutations in the SMN1 gene resulting in reduced levels of the SMN protein. Nusinersen, the first antisense oligonucleotide (ASO) approved for SMA treatment, binds to the SMN2 gene, paralogue to SMN1, and mediates the translation of a functional SMN protein. Here, we used longitudinal high-resolution mass spectrometry (MS) to assess both global proteome and metabolome in cerebrospinal fluid (CSF) from ten SMA type 3 patients, with the aim of identifying novel readouts of pharmacodynamic/response to treatment and predictive markers of treatment response. Patients had a median age of 33.5 [29.5; 38.25] years, and 80% of them were ambulant at time of the enrolment, with a median HFMSE score of 37.5 [25.75; 50.75]. Untargeted CSF proteome and metabolome were measured using high-resolution MS (nLC-HRMS) on CSF samples obtained before treatment (T0) and after 2 years of follow-up (T22). A total of 26 proteins were found to be differentially expressed between T0 and T22 upon VSN normalization and LIMMA differential analysis, accounting for paired replica. Notably, key markers of the insulin-growth factor signaling pathway were upregulated after treatment together with selective modulation of key transcription regulators. Using CombiROC multimarker signature analysis, we suggest that detecting a reduction of SEMA6A and an increase of COL1A2 and GRIA4 might reflect therapeutic efficacy of nusinersen. Longitudinal metabolome profiling, analyzed with paired t-Test, showed a significant shift for some aminoacid utilization induced by treatment, whereas other metabolites were largely unchanged. Together, these data suggest perturbation upon nusinersen treatment still sustained after 22 months of follow-up and confirm the utility of CSF multi-omic profiling as pharmacodynamic biomarker for SMA type 3. Nonetheless, validation studies are needed to confirm this evidence in a larger sample size and to further dissect combined markers of response to treatment., (© 2023. The Author(s).)

Introduction: Persistent cloaca, defined as confluence of the rectum, the vagina and the urethra into a single common channel, has an estimated incidence of 1/50,000 live births. We describe the buccal mucosa graft vaginoplasty for a 11 year old female with cloaca, who underwent at the age of 11 months a Peña repair. We performed the vaginoplasty after the onset of uterine pain due to the beginning of menstruation., Material and Methods: We accessed the lower lip for superficial dissection to harvest the graft. The donor site has been kept with as much submucosal fat as possible to avoid damage to the buccinatoria muscles. A second graft was further obtained from the cheek. Both grafts were submitted to multiple small sections to produce a mesh graft and increase its size. A arciform incision anterior to the anal canal and posterior to the urethra was performed followed by consecutive dissection with eletrocautery to gain profundity. The mesh-graft was placed over the neovaginal cavity and sutured with 4.0 PDS monofilament suture used to suture and then quilt the graft in place. The vaginal capacity was confirmed by ease of a two-digit insertion. Haemostasis was confirmed before the insertion of a soft vaginal mold. The patient remained with an indwelling urinary catheter. The mold was equivalent to 24Fr and had 13 cm of profundity and Foley tube were removed after 14 days postoperatively., Results: Patient had an excellent postoperative course and had been instructed to perform vaginal dilatation every 3 h during the day. Current follow up is 10 months., Discussion: Buccal mucosal grafting has advantages over the use of keratinized skin flaps and intestinal flaps. Buccal mucosa is ideal for female genital reconstruction, given its color, texture, lack of hair and mild mucous production. In our particular case, we connected the neovagina after two months of adequate healing to the native 1⁄3 through laparoscopic approach., Conclusions: BMG vaginoplasty is a viable alternative to treat females with cloaca at adolescence., (Copyright © 2023 Journal of Pediatric Urology Company. Published by Elsevier Ltd. All rights reserved.)

Advanced quantitative bioanalytical approaches in combination with network analyses allow us to answer complex biological questions, such as the description of changes in protein profiles under disease conditions or upon treatment with drugs. In the present work, three quantitative proteomic approaches-either based on labelling or not-in combination with network analyses were applied to a new in vitro cellular model of nonalcoholic fatty liver disease (NAFLD) for the first time. This disease is characterized by the accumulation of lipids, inflammation, fibrosis, and insulin resistance. Hepatic G2 cells were used as model, and NAFLD was induced by a complex of oleic acid and bovine albumin. The development of the disease was verified by lipid vesicle staining and by the increase in the expression of perilipin-2-a protein constitutively present in the vesicles during NAFLD. The nLC-MS/MS analyses of peptide samples obtained from three different proteomic approaches resulted in accurate and reproducible quantitative data of protein fold-change expressed in NAFLD versus control cells. The differentially regulated proteins were used to evaluate the involved and statistically enriched pathways. Network analyses highlighted several functional and disease modules affected by NAFLD, such as inflammation, oxidative stress defense, cell proliferation, and ferroptosis. Each quantitative approach allowed the identification of similar modulated pathways. The combination of the three approaches improved the power of statistical network analyses by increasing the number of involved proteins and their fold-change. In conclusion, the application of advanced bioanalytical approaches in combination with pathway analyses allows the in-depth and accurate description of the protein profile of an in vitro cellular model of NAFLD by using high-resolution quantitative mass spectrometry data. This model could be extremely useful in the discovery of new drugs to modulate the equilibrium NAFLD health state.

Introduction: Diphallia is a rare anomaly. It has a range of appearances from a small accessory penile to complete duplication., Methods: We present a 2 year-old boy with complete penile duplication. The left penile was the largest. NMR (Nuclear Magnetic Resonance) suggested one corporal body for each penile and VCUG (Voiding Cystourethrogram) showed a normal urethra in the right penile and stricture at glandular and mid penile urethra of the left penis. A Y confluence to bulbar urethra was observed confirming only one prostate and bladder., Results: The cystoscopy through the right penile identified the urethral confluence in the bulbar area. We performed a meatotomy in the left penile to insert the cystoscope and confirmed the blind ending urethra. We decided to remove this penile. The penile was degloved entirely and clamped and took out the corpora at the base., Discussion: Diphallia can have three presentations: only glans duplication, bifid diphallia and complete diphallia (two corpora cavernosa and a corpus spongiosum for each penile). In our case, each penile presented only one corpora cavernosa and the decision taken was based on urethral patency., Conclusion: The treatment should always be planned individually whereas associated anomalies with the goal of attaining satisfactory functional and cosmetic results., (Copyright © 2022 Journal of Pediatric Urology Company. Published by Elsevier Ltd. All rights reserved.)

Introduction: A challenging situation in proximal hypospadias is the presentation of patients with successful urethroplasty but with persistent or recurrent ventral curvature (VC) after multiple hypospadias repair., Materials and Methods: We present a 13 year-old boy with 7 previous surgeries (long TIP, Duplay, meatoplasty) to treat hypospadias presenting with 60 degrees of VC, in spite of a well-accepted coronally neomeatus. We degloved the penis and artificial erection clearly appointed corporal disproportion causing curvature. We disconnected urethra from corpora. After excision of remnant fibrotic tissue, there was a residual curvature so a lenghtening corporoplasty with dermal graft from groin was performed. We have adjusted the urethral meatus position into a proximal penile shaft. We used a buccal mucosa graft placed in an inverted U-shape position planning a second stage urethroplasty (1). An indwelling silicone Foley tube was left for one week. The patient was discharged the day after surgery., Results: The aspect after corporoplasty proved satisfactory curvature correction. Patient had an excellent outcome and is scheduled for a second-stage after 6 months., Discussion: Snodgrass and Bush (2) reported that on 73 patients with an average of 2.7 operations for proximal shaft to perineal hypospadias; of which, 83% had VC at re-operation averaging 50°. We do believe that some good results with minimal dorsal plicature may recur in adolescence and therefore when these procedures may be considered, they should be performed by classic Nesbit technique (3). Otherwise, the choice for primary ventral lengthening should be taken., Conclusion: Severe curvature associated with hypospadias should undergo a major procedure at early stage to avoid decompensation after dorsal plicature in adolescence. We had a very satisfactory result, the patient awaits the second stage procedure (Figure-1)., Competing Interests: None declared., (Copyright® by the International Brazilian Journal of Urology.)

Introduction: Antegrade continence enema (ACE) is recommended for patients with fecal incontinence/constipation refractory to conservative management. The Malone ACE utilizes the appendix as a catheterizable channel whereas the Macedo-Malone (MM) precludes the use of the appendix. We aimed to illustrate the MM procedure., Methods: The left colon is brought out through a small transverse incision on the upper left abdomen and a 3-cm transverse flap in a tenia is created. A 12-Fr silicone Foley catheter is placed on the mucosal surface of the flap to allow creating a tubular conduit. After closure of the anterior wall colonic, the continence valve mechanism is produced by embedding the tube over a serous lined tunnel created by interrupted sutures. The distal portion of the tube is anastomosed into a V shape to the skin flap to avoid stoma stenosis., Discussion: The advantage of this technique is the all-the time availability for not requiring the appendix which some authors prefer to use for urinary reconstruction. In a previous study, we have shown that the MM produces a high rate (89%) of fecal continence (Mean follow-up: 75 months)., Conclusion: We are convinced that this procedure can be incorporated into fecal incontinence/constipation armamentarium., (Copyright © 2021 Journal of Pediatric Urology Company. Published by Elsevier Ltd. All rights reserved.)

Introduction: The purpose of this study was to determine the incidence of lower urinary tract surgery in patients with myelomeningocele (MMC) operated in utero as well as in the subgroup of patients with a minimum age of 5 years., Methods: We use a previously published protocol to categorize bladder patterns and propose the treatment: high risk pattern-anticholinergics and clean intermittent catheterization (CIC); incontinent and normal patterns-clinical surveillance and underactivity pattern- CIC. Non-response to clinical treatment with maintenance of detrusor pressure higher than 40 cmH20 with worsening of hydronephrosis or recurrent urinary infection were imperative indications for surgery and urinary incontinence due to sphincter deficiency and leakage pressure below 40 cmH20 in patients aged 5 years and older were possible indications too. We identified the prevalence of urinary tract surgery and concomitant treatment of constipation and refractory fecal incontinence by convenience, the technique performed and surgery outcomes., Results: A total of 122 patients are part of the prospective protocol. The first UE was performed in 119 patients (median age of 4 months). The categorization of the bladder pattern was high risk in 52.1%, incontinent in 25.2%, hypocontractile 4.2% and normal in 18.5%. Current follow-up was 29.9 months (1-99 months). Surgery was performed on 10 patients (8.4%): 3 vesicostomies, 2 surgeries to treat vesicoureteral reflux, 6 bladder augmentations, 3 ACE and a sling surgery. Considering only patients older than 5 years, we identified 65 patients and seven surgeries performed (10.8%)., Discussion: Most bladder reconstruction studies are case series of single institutions or cooperative services, most of which are retrospective. The prospective clinical interpretation and imaging and urodynamic exams over time allowed us prospectively to define the risk of surgery in patients with myelomeningocele operated in utero. It must be considered that the response to the initial urological treatment and even the failure that leads to the need for surgery have to be evaluated in a context of follow-up time. For this reason we have studied separately patients over 5 years-old and also the group considered to be at greatest risk for surgery, the high-risk group of the categorization already described., Conclusion: We found an incidence of 10.8% of surgeries in patients over 5 years-old and 12.9% for the high-risk group. This information may be useful to educate parents when stating urological treatment., (Copyright © 2021 Journal of Pediatric Urology Company. Published by Elsevier Ltd. All rights reserved.)

Introduction: Distal hypospadias represent the most frequent clinical presentation of hypospadias. In spite of more than 300 techniques available, there is not an ideal approach. We have proposed an alternative procedure based on the combination of minor urethral mobilization and major glans deconstruction and partial disassembly from the corpora, the GUD technique. We want to present our clinical experience with the procedure and describe it in detail., Methods: The technique consists of disconnecting the spongious tissue and the distal urethra from the corpora and detaching partially the glans as well, from 2 to 10 o'clock. The glans is opened in midline and the procedure combines cranially mobilization of urethra with caudal and medial rotation of glans wings to refurbish the glans correcting the hypospadia without urethroplasty., Results: We have treated 164 patients with distal hypospadia. Median age at the surgery was 22.4 months (1-184 months). The meatal position after penile degloving was coronal at 108 cases, subcoronal at 54 and 2 patients presented megameatus and intact foreskin. Three patients (1.8%) had mild penoscrotal transposition in addition to hypospadia. Twenty-eight patients were treated as a secondary repair (17%). We found complications in 6 patients (3.6%) consisting of five fistulas (3%) and three glans dehiscence (1.8%). Two patients had both complications. Follow up was 21 months (1-42 months) and the median follow-up time was 18 months., Discussion: We acknowledge that this procedure is intended only to distal hypospadias (coronal and subcoronal). We stress that the GUD procedure can be performed irrespectively of any urethral plate "quality" as it does not require a minimum glans width as the TIP repair. Moreover, there is no need for preoperative testosterone treatment. The absence of suture and urethroplasty minimizes the risk of coronal fistulas after surgery., Conclusions: We believe that this procedure is a viable alternative to distal hypospadias repair., Competing Interests: Conflict of interest None., (Copyright © 2021 Journal of Pediatric Urology Company. Published by Elsevier Ltd. All rights reserved.)

In this study we investigated the performance of a computational pipeline for protein identification and label free quantification (LFQ) of LC-MS/MS data sets from experimental animal tissue samples, as well as the impact of its specific peptide search combinatorial approach. The full pipeline workflow was composed of peptide search engine adapters based on different identification algorithms, in the frame of the open-source OpenMS software running within the KNIME analytics platform. Two different in silico tryptic digestion, database-search assisted approaches (X!Tandem and MS-GF+), de novo peptide sequencing based on Novor and consensus library search (SpectraST), were tested for the processing of LC-MS/MS raw data files obtained from proteomic LC-MS experiments done on proteolytic extracts from mouse ex vivo liver samples. The results from proteomic LFQ were compared to those based on the application of the two software tools MaxQuant and Proteome Discoverer for protein inference and label-free data analysis in shotgun proteomics. Data are available via ProteomeXchange with identifier PXD025097., (© 2021 The Authors. Proteomics published by Wiley-VCH GmbH.)

Introduction: We present a different salvage procedure for penile prosthesis implantation in a De Castro neophallus., Methods: A patient with congenital aphallia had been operated at the age of 11. Ten years later he had two non successful attempts of prosthesis implantation. Surgery consisted of adapting the implants into the aortic graft and folding it in the middle over the cylinders to reinforce its strength., Results: Patient had a successful postoperative course and has now 6 months of follow-up., Discussion: In a systematic review of penile prosthetic outcomes and complications in gender-affirming surgery, most of the prostheses were inflatable (83.6%) and single-cylinder (61.0%). At a mean follow-up of 3.0 years: 36.2% of prosthesis complications, 60.0% of patients had their original implant present and 83.9% reported achieving penetration. We decided to use vascular grafts as a scaffold because of former non successful attempts., Conclusion: The use of vascular prosthesis as a device to implant the penile prosthesis seems to be a safe and effective alternative in an attempt to offer erectile function to the neophallus in case of congenital aphallia., Competing Interests: Conflicts of interest None., (Copyright © 2021 Journal of Pediatric Urology Company. Published by Elsevier Ltd. All rights reserved.)

Competing Interests: None declared.

Background: Choline kinase-α (ChoKα/CHKA) overexpression and hyper-activation sustain altered choline metabolism conferring the cholinic phenotype to epithelial ovarian cancer (OC), the most lethal gynecological tumor. We previously proved that CHKA down-modulation reduced OC cell aggressiveness and increased sensitivity to in vitro chemotherapeutics' treatment also affecting intracellular content of one-carbon metabolites. In tumor types other than ovary, methionine decrease was shown to increase sensitivity to tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)-receptor 2 triggering. These effects were suggestive of a potential role for ChoKα in regulating susceptibility to TRAIL cytokine., Methods: The relationship between ChoKα/CHKA and TRAIL-receptor 2 (TRAIL-R2) expression was investigated in silico in OC patients' GEO datasets and in vitro in a panel of OC cell lines upon transient CHKA silencing (siCHKA). The effect of siCHKA on metabolites content was assessed by LC-MS. The triggered apoptotic signalling was studied following soluble-TRAIL or anti-TRAIL-R2 agonist antibody treatment. Lipid rafts were isolated by Triton X-100 fractionation. Preclinical ex vivo studies were performed in OC cells derived from patients' ascites using autologous PBLs as effectors and a bispecific anti-TRAIL-R2/anti-CD3 antibody as triggering agent., Results: Here we demonstrate that siCHKA specifically overcomes resistance to TRAIL-mediated apoptosis in OC cells. Upon siCHKA we detected: a significant sensitization to caspase-dependent apoptosis triggered by both soluble TRAIL and anti-TRAIL-R2 agonist antibody, a specific increase of TRAIL-R2 expression and TRAIL-R2 relocation into lipid rafts. In siCHKA-OC cells the acquired TRAIL sensitivity was completely reverted upon recovery of ChoKα expression but, at variance of other tumor cell types, TRAIL sensitivity was not efficiently phenocopied by methionine deprivation. Of note, we were also able to show that siCHKA sensitized tumor cells derived ex vivo from OC patients' ascites to the cytotoxic activity of autologous lymphocytes redirected by a bispecific anti-TRAIL-R2/anti-CD3 antibody., Conclusions: Our findings suggest that ChoKα/CHKA impairment, by restoring drug-induced or receptor-mediated cell death, could be a suitable therapeutic strategy to be used in combination with chemotherapeutics or immunomodulators to improve OC patients' outcome.

Competing Interests: None declared.

Aims: To evaluate the effects of high intra-abdominal pressure (IAP) during hyperthermic intraperitoneal chemotherapy (HIPEC) on cisplatin uptake by residual tumor and normal tissues, pharmacokinetics, and short-term surgical outcomes., Patients & Methods: Patients with peritoneal metastasis from colorectal cancer or pseudomyxoma peritonei were randomized to closed-abdomen HIPEC with low-IAP or high-IAP, after complete cytoreduction. High-IAP was obtained increasing the volume of perfusate maintaining constant the cisplatin concentration (42 mg/L). We determined the Platinum concentration using an Inductive Coupled Plasma Mass Spectrometry System. Randomization was stratified according to tumor type. To consider the multiple sampling in the three tissues types of interest, we performed linear mixed models to assess the differences of cisplatin concentration between study arms. We also compared AUC perfusate/plasma ratios (Wilcoxon-Mann-Whitney) and perioperative severe complication rates (chi-square) between study arms., Results: 38 cases were randomly assigned to IAP arms (n = 19 each). Median IAPs were 19 mmHg and 11 mmHg in the high and low arms, respectively. Cisplatin concentrations did not differ in the tumor residual tissues and in the muscular fascia [22.8 ng/mg (SD: 25.5) vs. 15.9 ng/mg (SD: 13.3), p = 0.181] and [50.3 ng/mg (SD: 40.1) vs. 42.0 ng/mg (SD: 38.3), p = 0.426, respectively], whereas in the mesenteric peritoneum it did [5.4 ng/mg (SD: 7.82) vs. 2.7 ng/mg (SD: 2.9), p = 0.048]. Pharmacokinetic advantage did not differ between the two arms. High-IAP did not increase perioperative severe complications rate (NCI-CTCAE.v3)., Conclusions: high-IAP HIPEC increases cisplatin distribution in the mesenteric peritoneum, is safe, and could be considered to obtain microscopic cytoreduction., (Copyright © 2019 Elsevier Ltd, BASO ~ The Association for Cancer Surgery, and the European Society of Surgical Oncology. All rights reserved.)

Introduction: We present an alternative procedure for distal hypospadias consisting of urethral mobilization and partial glandar disassembly, namely GUD (glandar urethral disassembly) technique., Materials and Methods: A subcoronal circumcision exposes distal dysplastic urethra. We incise the Buck´s fascia on both sides of urethra releasing it partially from the corpora. We keep a thin bridge of urethral plate to the glans and disassembly almost completely the glans from the corpora, except for the bridge. The glans is incised creating two wide wings that are extremely mobile. The urethra is mobilized, advanced and sutured to the tip of the glans. The glans wings embrace the distal urethra producing a conical glans., Discussion: Koff et al. published a modification of the Barcat technique known as extensive urethral mobilization and confirmed excellent cosmetic and functional results on 168 patients with only 3.5% of reoperation. This procedure has several modifications but none has reported an aggressive disconnection of corpora to the glans, but simply incising two glans wings. Mitchell & Blagi and Perovic et al. reported on complete penile disassembly for epispadia repair as a way to complete release of the rotation of the penis and treat dorsal chordee. We joined these two procedures to propose the GUD technique. The rationale for this procedure is to avoid suture urethroplasty and create a more conical and cosmetic glans., Conclusion: We are convinced that this operation can be regarded as a genuine alternative to distal hypospadias (coronal and subcoronal) but should not be addressed to midshaft forms., Competing Interests: None declared., (Copyright® by the International Brazilian Journal of Urology.)

Background: cytoreduction surgery (CRS) and heated intraperitoneal chemotherapy (HIPEC) is currently the standard of care for some peritoneal surface malignancies. There is experimental evidence supporting that high Intra Abdominal Pressure (IAP) during HIPEC could enhance the uptake of drugs by tumor tissues. However, few papers are describing the hemodynamic and respiratory effects of increased IAP during HIPEC., Aims: to evaluate the hemodynamic and respiratory association with different IAPs during HIPEC., Methods: This is part of an IRB board approved prospective randomized controlled trial conducted at The National Tumor Institute of Milan from 2014 to 2017 (NCT0294979). Patients diagnosed with Pseudomyxoma (PMP) or Peritoneal Metastasis of Colorectal Cancer (PM-CRC) were submitted to CRS and then randomized to receive low IAP (8-12 mmHg) or high IAP (18-22 mmHg) HIPEC. Hemodynamic and respiratory data were collected in eight different time-points during the whole procedure., Results: 33 patients (n low = 15, n high = 18) with PM-CRC and PMP were analysed. The mean IAP in the low IAP HIPEC group was 11.4 mmHg (SD: 2.5) and 18.1 mmHg (SD: 2.5) in the high IAP HIPEC group (p«0.001). There was no difference in the hemodynamic parameters between both groups, except for the central venous pressure (CVP) that was significantly higher in the high IAP group (p = 0.006). High IAP was well tolerated in the experimental arm with no hemodynamic and ventilation instability observed during the intervention., Conclusion: We conclude that high IAP at the level of 18-22 mmHg during HIPEC has no significant hemodynamic parameters difference, being feasible and safe in our study., (Copyright © 2020 Elsevier Ltd, BASO ~ The Association for Cancer Surgery, and the European Society of Surgical Oncology. All rights reserved.)

Introduction: Bladder exstrophy remains one of the most challenging abnormalities in pediatric urology. We propose bladder neck transection and bladder augmentation with a catheterizeable reservoir technique to achieve continence after previous anatomic reconstruction in stages., Methods: At the age of 5-6 years, we offer the transection of bladder neck and enterocystoplasty to achieve continence. We report on a 6-year-old boy that underwent this procedure. We perform the reservoir from ileum according to Macedo-technique that constructs a catheterizeable channel from the same bowel segment. The continence mechanism of the efferent tube is based on angulation and a serous lined tunnel created with 3.0 prolene sutures. The stoma is placed in the midline., Results: Patient had an uneventful evolution and is continent performing CIC every 4 h with 9 months of follow up., Discussion: In spite of continuous development of bladder exstrophy surgery, the urethral continence and voluntary micturition is still not possible in the majority of patients. We discuss with our patients honestly and offer this method as a viable alternative to achieve continence., Conclusion: In our experience, most patients accept urethral transection and suprapubic CIC when educated about results with other alternatives of bladder neck plasty., (Copyright © 2020 Journal of Pediatric Urology Company. Published by Elsevier Ltd. All rights reserved.)

Purpose: In utero myelomeningocele closure is a valid alternative to postnatal repair with unclear benefits to bladder function. We compared bladder status in patients who underwent fetal myelomeningocele surgery versus postnatal repair., Materials and Methods: We retrospectively reviewed our database, with group 1 consisting of in utero surgery and group 2 consisting of postnatal repair. Group 3 was a subgroup of group 2, including patients initially presenting at age less than 12 months. We recorded medical history, radiological investigation with renal ultrasonography, voiding cystourethrography, urodynamic evaluation and clinical outcome of the bladder pattern after treatment., Results: We identified 88 patients in group 1, 86 in group 2 and 38 in group 3. The incidence of urinary tract infection was higher in the postnatal period (45% vs 20%). Hydronephrosis occurred in 20.7%, 22.6% and 28.9% of patients in groups 1, 2 and 3, respectively. Vesicoureteral reflux was diagnosed in 15% in all groups. Urodynamic data showed a higher prevalence of detrusor overactivity in group 1 and no difference in other urodynamic parameters. The high risk bladder pattern at initial evaluation occurred in 56%, 50% and 46% of patients in groups 1, 2 and 3, respectively. There was a trend to decrease the percentages of the high risk bladder pattern and to increase the normal pattern after treatment in all groups., Conclusions: In utero repair did not improve urological parameters compared to repair in the postnatal period.

Objectives: To evaluate the first 100 cases of in utero myelomeningocoele (MMC) repair and urological outcomes in a prospective analysis aiming to define possible improvement in bladder function., Patients and Methods: We used a protocol consisting of a detailed medical history, urinary tract ultrasonography, voiding cystourethrography, and urodynamic evaluation. Patients were categorised into four groups: normal, high risk (overactive bladder with a detrusor leak-point pressure >40 cm H 2 O and high filling pressures also >40 cm H 2 O), incontinent, and underactivity (underactive bladder with post-void residual urine), and patients were treated accordingly., Results: We evaluated 100 patients, at a mean age of 5.8 months (median 4 months), classified as high risk in 52.6%, incontinent in 27.4%, with underactive bladder in 4.2%, and only 14.7% had a normal bladder profile. Clean intermittent catheterisation was initiated in 57.3% of the patients and anticholinergics in 52.6%. Antibiotic prophylaxis was initiated in 19.1% of the patients presenting with vesico-ureteric reflux., Conclusion: The high incidence of abnormal bladder patterns suggests little benefit of in utero MMC surgery concerning the urinary tract., (© 2018 The Authors BJU International © 2018 BJU International.)

Introduction: After the successful results of in utero myelomeningocele (MMC) repair presented by the Management of Myelomeningocele Study, the concept of fetal surgery was introduced in our institution in 2011. Since then, we have been able to follow prospectively a group of patients with attention to urological care. In the present study, we were interested in estimating urinary and fecal continence in this new subset of patients., Material and Methods: We selected from our database patients aged 5 years or older for evaluation of urinary and fecal continence. We reviewed all charts and completed a questionnaire to study aspects of urinary and fecal continence., Results: We identified 14 patients, i.e., 4 (28.6%) males and 10 (71.4%) females. The mean age at MMC surgery was 25.6 gestational weeks. The uro-dynamic class was high-risk in 6 (42.9%), incontinent in 4 (28.6%), hypocontractile in 1 (7.1%), and normal in 3 (21.4%) patients. Three patients had undergone surgery (2 augmentations, i.e., 1 in association with a left colon ACE Macedo-Malone procedure and 1 mini-sling urethroplasty). Twelve patients underwent clean intermittent catheterization (CIC) (85.7%). Only 3 (21.4%) patients had no urinary leakage. Eleven patients (78.6%) used diapers. Eight patients (57.2%) underwent retrograde rectal irrigation and 11 (78.6%) complained of fecal loss. Eleven patients (78.6%) did not report an impact on their self-esteem., Conclusion: Despite the use of CIC in 85.7% of the cases, the continence rate in MMC patients operated on in utero was low and 78.6% of the patients used diapers. This data can be used to educate parents about future conditions of their 5-year-old children and may stimulate the debate regarding further attempts (surgical or not) to improve fecal and urinary continence., (© 2019 S. Karger AG, Basel.)