Efficacy of Three Different Injection Techniques for the Endoscopic Treatment of Vesicoureteral Reflux (VUR) in Children: A Review of 10 Years of Experience.

Aim: To review our 10 years of experience with the endoscopic treatment of vesicoureteral reflux (VUR) in children, emphasizing the long-term efficacy of the "combined STING-HIT" technique. Materials and Methods: A retrospective study was performed including all children with symptomatic VUR undergoing the cystoscopic injection of bulking agents from January 2013 to December 2022 in our pediatric tertiary referral center. Three different endoscopic techniques were adopted: the "combined STING-HIT" technique, the STING technique, and the HIT technique. Treatment success was defined as symptom remission and VUR resolution on the voiding cystourethrogram (VCUG) performed at the 3-month follow-up. Results: In the study period, 140 (F:M = 64:76) patients and 228 ureters were treated at a median patient age of 3 (2.0-6.0) years. After a single endoscopic treatment, VUR resolved in 203 (88%) ureters. The VUR resolution rate after a single endoscopic treatment was 95% (n=70/74) in case of I-II VUR, 88% (n=87/99) in case of III VUR; 83% (n=38/46) in case of IV VUR; 89% (n=8/9) in case of V VUR (p-value: 0.174). Overall, one or two endoscopic treatments succeeded in 219 (96%) ureters. The overall VUR resolution rate following one or two endoscopic treatments was 100% (74/74) in case of I-II VUR, 93% (n=92/99) in case of III VUR; 96% (n=44/46) in case of IV VUR; 100% (n=9/9) in case of V VUR (p-value: 0.083). Despite not being statistically significant, the VUR resolution rate was higher for the "combined STING-HIT" technique, both after one (92%: n=110/119; versus 85%; n=62/73 versus 86%; n=31/36; p-value: 0.225) or two (98%: n=116/119; versus 95%; n=69/73 versus 94%; n=34/36; p-value: 0.469) endoscopic treatments. Conclusion: The endoscopic approaches were highly successful for the treatment of VUR in children. The "combined STING-HIT" technique was a safe and effective procedure, being associated with the higher resolution rate.

Multidisciplinary Management of Children with Occult Spinal Dysraphism: A Comprehensive Journey from Birth to Adulthood.

Occult spinal dysraphism (OSD) comprises different forms of failure in embryogenic development that can lead to genitourinary, spinal, or lower limb alterations, thus determining progressive neurological deterioration. The correct management of children harboring OSD represents a significant issue during their life up to adulthood. However, patients often have to entertain individual consultations with each specialist. We settled on a multidisciplinary team comprising pediatric neurosurgeons, urologists, neurologists, orthopedists, and other supporting physicians. We present the results of such actions by analyzing a series of 141 children with OSD subjected to neurosurgical procedures, evaluating the impact of multidisciplinary management on outcomes. We also evaluated the specific actions according to the different ages of OSD patients from birth to adulthood to provide a schematic plan that could represent a basis for establishing and disseminating the need for a multidisciplinary approach in OSD management. The multidisciplinary team allows all consultants to see the patient together, covering specific aspects of history and examination pertinent to their management. Offering a one-stop service prevents coordination issues between the different medical teams, avoids delays or cancellations of the various appointments, optimizes cost-effectiveness, and improves efficiency and parents' satisfaction.

Topographic volume-standardization atlas of the human brain.

Specific anatomical patterns are seen in various diseases affecting the brain. Clinical studies on the topography of pathologies are often limited by the absence of a normalization of the prevalence of pathologies to the relative volume of the affected anatomical structures. A comprehensive reference on the relative volumes of clinically relevant anatomical structures serving for such a normalization, is currently lacking. The analyses are based on anatomical high-resolution three-dimensional T1-weighted magnetic resonance imaging data of 30 healthy Caucasian volunteers, including 14 females (mean age 37.79 years, SD 13.04) and 16 males (mean age 38.31 years, SD 16.91). Semi-automated anatomical segmentation was used, guided by a neuroanatomical parcellation algorithm differentiating 96 structures. Relative volumes were derived by normalizing parenchymal structures to the total individual encephalic volume and ventricular segments to the total individual ventricular volume. The present investigation provides the absolute and relative volumes of 96 anatomical parcellation units of the human encephalon. A larger absolute volume in males than in females is found for almost all parcellation units. While parenchymal structures display a trend towards decreasing volumes with increasing age, a significant inverse effect is seen with the ventricular system. The variances in volumes as well as the effects of gender and age are given for each structure before and after normalization. The provided atlas constitutes an anatomically detailed and comprehensive analysis of the absolute and relative volumes of the human encephalic structures using a clinically oriented parcellation algorithm. It is intended to serve as a reference for volume-standardization in clinical studies on the topographic prevalence of pathologies.

High-pressure balloon dilatation in children: our results in 30 patients with POM and the implications of the cystoscopic evaluation.

Primary Obstructive Megaureter (POM) is a common cause of hydronephrosis in children with spontaneous resolution in most cases. High-Pressure Balloon Dilatation (HPBD) has been proposed as a minimally invasive procedure for POM correction in selected patients. The aim of the paper is to review our experience with HPBD in patients with POM. We performed a retrospective study in a single Centre collecting data on patients' demographics, diagnostic modalities, surgical details, results and follow-up. In particular, the endoscopic aspect of the orifice permitted the identification of 3 patterns: adynamic ureteral segment, stenotic ureteric ring and pseudoureterocelic orifice. We performed HPBD in 30 patients over 6 years. We had 23 patients with adynamic distal ureteral segment (type 1), 4 with stenotic ring (type 2) and 3 with ureterocelic orifice (type 3). In 3 patients (10%) the guidewire did not easily pass into the ureter requiring ureteral stenting or papillotomy. Post-operative course was uneventful. Five patients (3 pseudoureterocelic) required open surgery during follow-up. HPBD for the treatment of POM is a safe and feasible procedure and it can be a definitive treatment of POM. Complications are mainly due to double J stent and none of our patients had symptoms related to vescico-ureteral reflux. The aspect of the orifice, identified during cystoscopy, seems to correlate with the efficacy of the dilatation: type 1 and 2 are associated with good and excellent results respectively; type 3 do not permit dilatation in almost all cases requiring papillotomy. HPBD can be performed in selected patients of all paediatric ages as first therapeutic line. The presence of a pseudoureterocelic orifice or long stenosis might interfere with the ureteral stenting and seems associated with worse outcomes.

Minimally Invasive Approaches in Pediatric Urolithiasis. The Experience of Two Italian Centers of Pediatric Surgery.

Background: Over the last 30 years, the incidence of pediatric urolithiasis (PU) has been increasing and the surgical management has evolved toward a minimally invasive approach (MIA). We reported the experience of two Centers of Pediatric Surgery in the management of PU, focusing on MIA as first choice in treatment. Methods: Data were retrospectively analyzed from October 2009 to October 2019 in children with urolithiasis who were admitted to two referral Italian Centers of Pediatric Surgery. Demographic and clinical data of the patients, features of the urolithiasis, type of surgery were considered. Results: Seventy patients (7.3 ± 5.0 years) with normal renal function were treated for calculi in the pyelocaliceal system (45.7%), ureter (34.3%), bladder (4.3%), urethra (1.4%), and multiple locations (14.3%). Size of calculi was >10 mm in 55.7% of cases (kidney>bladder/urethra>multiple>ureter, p = 0.01). Symptoms were present in 75.7% of patients. Family history was positive in 16.9% of cases. MIA was performed in 59 patients (84.3%): 11.8% shockwave lithotripsy (kidney>ureter>multiple); 32.2% ureteral retrograde surgery (ureteral>other localizations); 30.5% retrograde intrarenal surgery (kidney>other localizations); and 25.4% other procedures including percutaneous nephrolithotomy, cystoscopic bladder stone removal or laser cystolithotripsy (kidney>bladder>multiple). Preoperative stenting was necessary in 52.8% of cases. Four MIA procedures (6.9%, kidney>ureter/multiple) were converted to open surgery. Open surgery was required as first approach in 15.7% of patients (kidney>ureter>multiple) who needed urgent surgery or had associated congenital renal anomalies. In 18/70 of children (25.7%), with prevalence of stones in kidney and multiple location (p < 0.01), a second procedure completed the treatment (88.8% MIA). Intraoperative difficulties were recorded in 8.5% of cases, without difference between location and size of calculi. Late complications (5.7%) were related to displacement and infection of the ureteral stent. Conclusions: MIA resulted to be feasible in more than 75% of primary surgery and in more than 85% of cases requiring a second procedure. Preoperative stent was mandatory in more than 50% of children. The technological evolution allowed to overcome many of the technical difficulties related to the approach to the papilla and lower calyxes. Open surgery is reserved for selected cases and endoscopic surgery represents the best choice of treatment for PU.

Topographic brain tumor anatomy drives seizure risk and enables machine learning based prediction.

OBJECTIVE: The aim of this study was to identify relevant risk factors for epileptic seizures upon initial diagnosis of a brain tumor and to develop and validate a machine learning based prediction to allow for a tailored risk-based antiepileptic therapy. METHODS: Clinical, electrophysiological and high-resolution imaging data was obtained from a consecutive cohort of 1051 patients with newly diagnosed brain tumors. Factor-associated seizure risk difference allowed to determine the relevance of specific topographic, demographic and histopathologic variables available at the time of diagnosis for seizure risk. The data was divided in a 70/30 ratio into a training and test set. Different machine learning based predictive models were evaluated before a generalized additive model (GAM) was selected considering its traceability while maintaining high performance. Based on a clinical stratification of the risk factors, three different GAM were trained and internally validated. RESULTS: A total of 923 patients had full data and were included. Specific topographic anatomical patterns that drive seizure risk could be identified. The involvement of allopallial, mesopallial or primary motor/somatosensory neopallial structures by brain tumors results in a significant and clinically relevant increase in seizure risk. While topographic input was most relevant for the GAM, the best prediction was achieved by a combination of topographic, demographic and histopathologic information (Validation: AUC: 0.79, Accuracy: 0.72, Sensitivity: 0.81, Specificity: 0.66). CONCLUSIONS: This study identifies specific phylogenetic anatomical patterns as epileptic drivers. A GAM allowed the prediction of seizure risk using topographic, demographic and histopathologic data achieving fair performance while maintaining transparency.

Urothelial carcinoma in children: A case series.

OBJECTIVE: To report a series of 5 patients with urothelial bladder cancer (UBC) three of them with a history of exposure to amines and only two with gross hematuria. MATERIALS AND METHODS: After obtaining ethical and legal authorization, we performed a restrospective monocentric study. We collected information of patients with UBC over a period of 10 years. We recorded: age, sex, reason for presentation, familial history and risk factors, preoperative assessment, surgical details, histological type and grade, follow-up. RESULTS: 2 children came to our attention for hematuria and 3 for incidental bladder mass finding, at a median age of 11.8 years. We performed microscopically complete transurethral resection of the tumor (TURB). Median tumor size was 1.8cm. No further therapy was required. All cancers belonged to NMIBC (Non-muscle-invasive Bladder Cancer) considering the 2004 WHO classification: 2 urothelial papillomas, 2 papillary tumors with low grade malignancy (PUN-LPM) and 1 papillary urothelial carcinoma of low histological grade (LG-PUC Ta, N0, M0). There was not any complications and no relapse occurred during follow-up (median 30 months). CONCLUSIONS: In this study, UBCs presenting at a young age were low-grade and have not recurred in follow-up. This confirms the results of other series reported in Literature. Therefore there might be the space to perform a follow-up dedicated to children.

Severe Dumping Syndrome in a 6-year-old Girl with Congenital Microgastria Treated by Hunt-Lawrence Pouch.

Microgastria is a rare congenital condition often associated with other anomalies. In the present report we describe the case of a 6-year-old girl with isolated CM who presented with dumping syndrome successfully treated by a Hunt-Lawrence pouch.

Effectiveness and properties of the biological prosthesis Permacol™ in pediatric surgery: A large single center experience.

INTRODUCTION: The use of prosthetic patches of non-absorbable materials represents a valid tool in the treatment of abdominal wall and diaphragmatic defects in pediatric age. In recent years research has developed biological dermal scaffolds made from a sheet of acellular matrix that can provide the desired support and reduce the occurrence of complications from non-absorbable implant. We present our experience and a systematic review to evaluate the use of biologic prosthesis for abdominal wall closure in pediatric patients. METHODS: The study from January 2009 to January 2015 involved 20 patients treated with Permacol™ implant. We observed postoperative complications only in patients treated for abdominal wall closure, which is the major indication for the use of Permacol™. We conducted a systematic review and meta-analysis (according to PRISMA) on PubMed/Medline, Scopus and EMBASE regarding the use of biological prosthesis in pediatric population considering the incidence of complications as the primary outcome. RESULTS: 3/20 patients experienced complications: 2 patients with skin necrosis healed conservatively and 1 of them developed laparocele. Thus only 1 patient with incisional hernia had significant surgery complication. In patients who were permanently implanted with Permacol™ it has not determined adverse reactions with optimal functional outcome. CONCLUSIONS: In accordance with the few data (case reports and case series) reported in literature about pediatric patients, our experience in different pathologies and applications has shown the effectiveness of Permacol™, in particular for the non-occurrence of infections, that often affect the use of prosthesis.

A novel polyclonal antibody library for expression profiling of poorly characterized, membrane and secreted human proteins.

The YOMICS™ antibody library (http://www.yomics.com/) presented in this article is a new collection of 1559 murine polyclonal antibodies specific for 1287 distinct human proteins. This antibody library is designed to target marginally characterized membrane-associated and secreted proteins. It was generated against human proteins annotated as transmembrane or secreted in GenBank, EnsEMBL, Vega and Uniprot databases, described in no or very few dedicated PubMed-linked publications. The selected proteins/protein regions were expressed in E. coli, purified and used to raise antibodies in the mouse. The capability of YOMICS™ antibodies to specifically recognize their target proteins either as recombinant form or as expressed in cells and tissues was confirmed through several experimental approaches, including Western blot, confocal microscopy and immunohistochemistry (IHC). Moreover, to show the applicability of the library for biomarker investigation by IHC, five antibodies against proteins either known to be expressed in some cancers or homologous to tumor-associated proteins were tested on tissue microarrays carrying tumor and normal tissues from breast, colon, lung, ovary and prostate. A consistent differential expression in cancer was observed. Our results indicate that the YOMICS™ antibody library is a tool for systematic protein expression profile analysis that nicely complements the already available commercial antibody collections.

The ubiquitin ligase HectH9 regulates transcriptional activation by Myc and is essential for tumor cell proliferation.

The Myc oncoprotein forms a binary activating complex with its partner protein, Max, and a ternary repressive complex that, in addition to Max, contains the zinc finger protein Miz1. Here we show that the E3 ubiquitin ligase HectH9 ubiquitinates Myc in vivo and in vitro, forming a lysine 63-linked polyubiquitin chain. Miz1 inhibits this ubiquitination. HectH9-mediated ubiquitination of Myc is required for transactivation of multiple target genes, recruitment of the coactivator p300, and induction of cell proliferation by Myc. HectH9 is overexpressed in multiple human tumors and is essential for proliferation of a subset of tumor cells. Our results suggest that site-specific ubiquitination regulates the switch between an activating and a repressive state of the Myc protein, and they suggest a strategy to interfere with Myc function in vivo.

Human geminin promotes pre-RC formation and DNA replication by stabilizing CDT1 in mitosis.

Geminin is an unstable inhibitor of DNA replication that negatively regulates the licensing factor CDT1 and inhibits pre-replicative complex (pre-RC) formation in Xenopus egg extracts. Here we describe a novel function of Geminin. We demonstrate that human Geminin protects CDT1 from proteasome-mediated degradation by inhibiting its ubiquitination. In particular, Geminin ensures basal levels of CDT1 during S phase and its accumulation during mitosis. Consistently, inhibition of Geminin synthesis during M phase leads to impairment of pre-RC formation and DNA replication during the following cell cycle. Moreover, we show that inhibition of CDK1 during mitosis, and not Geminin depletion, is sufficient for premature formation of pre-RCs, indicating that CDK activity is the major mitotic inhibitor of licensing in human cells. Taken together with recent data from our laboratory, our results demonstrate that Geminin is both a negative and positive regulator of pre-RC formation in human cells, playing a positive role in allowing CDT1 accumulation in G2-M, and preventing relicensing of origins in S-G2.