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To offer an up-to-date appraisal of the current status of enhanced recovery after surgery (ERAS) protocols in pediatric urology and to provide a guide for the clinical urologist.We performed a comprehensive literature search and scoping review on ERAS protocols in pediatric urology using Pubmed (from 1946), Cochrane library, and MEDLINE to December 2021 with the terms ''enhanced recovery'', ''protocolised care'', ''post-operative protocol", ''fast-track surgery'' and ''pediatric urology". Studies were excluded if they did not include perioperative intervention related to urological procedures, no full-text available and in non-English language.To date, eight clinical studies (involving 1153 patients) have been published on ERAS protocols in pediatric urology. The patients involved ranged from neonates to adolescents, and the urological procedures included bladder augmentation, the Mitrofanoff procedure, laparoscopic pyeloplasty, laparoscopic nephrectomy, hypospadias repair, etc. Multidisciplinary components such as surgical and anesthetic considerations have been employed in ERAS protocols. The length of hospital stay was significantly lower in the ERAS groups with earlier enteral feeding resumption and return of bowel function in pediatric urology patients. The implementation of ERAS protocols does not result in higher complication and readmission rates; instead, some studies have even demonstrated a significant reduction in complication occurrence.ERAS is novel to pediatric urology with a limited scale of published data in the literature. Initial clinical studies revealed that ERAS appears to be efficacious in the field of pediatric urology. Further prospective studies formulating a standardized multimodal protocol are encouraged to better understand key components of ERAS and incorporate ERAS into clinical practice to optimize surgical outcomes for pediatric urology procedures.

Background Laparoscopic inguinal hernia repair is one of the procedures most commonly performed by paediatric surgeons. Current research on the learning curve for laparoscopic hernia repair in children is scarce. This study aims to evaluate the clinical outcome and learning curve of laparoscopic intra-corporeal inguinal hernia repair in children. Methods A retrospective single-centre analysis of all paediatric patients who underwent laparoscopic intra-corporeal inguinal hernia repair between 2010 and 2019 was performed. The clinical outcomes were analysed. The data on the achievement of the learning curve by surgical trainees were evaluated with the CUSUM technique, focusing on operative time. Results There were 719 patients with laparoscopic intra-corporeal inguinal hernia repair (comprising 1051 sides) performed during the study period. The overall ipsilateral recurrence rate was 1.8% without other complications detected. CUSUM analysis showed that there were 3 phases of training, for which the trainees underwent initial learning phase (Phase 1) for the first 7 cases. After mastering of the skills and extrapolating the skills to male patients with smaller body size (Phase 2), they then achieved performance comparable to that of the senior surgeons after 18 procedures (Phase 3). Conclusions 18 procedures seem to be the number required to reach the learning curve plateau in terms of operative time by surgical trainees. The clinical outcomes show that laparoscopic intra-corporeal inguinal hernia repair is a safe and transferrable technique, even in the hands of trainees, with adequate supervision and careful case selection. It also provides skill acquisition for minimally invasive surgery.

Summary Enteroviruses, such as EV-A71 and CVA16, mainly infect the human gastrointestinal tract. Human coronaviruses, including SARS-CoV and SARS-CoV-2, have been variably associated with gastrointestinal symptoms. We aimed to optimize the human intestinal organoids and hypothesize that these optimized intestinal organoids can recapitulate enteric infections of enterovirus and coronavirus. We demonstrate that the optimized human intestinal organoids enable better simulation of the native human intestinal epithelium, and that they are significantly more susceptible to EV-A71 than CVA16. Higher replication of EV-A71 than CVA16 in the intestinal organoids triggers a more vigorous cellular response. However, SARS-CoV and SARS-CoV-2 exhibit distinct dynamics of virus-host interaction; more robust propagation of SARS-CoV triggers minimal cellular response, whereas, SARS-CoV-2 exhibits lower replication capacity but elicits a moderate cellular response. Taken together, the disparate profile of the virus-host interaction of enteroviruses and coronaviruses in human intestinal organoids may unravel the cellular basis of the distinct pathogenicity of these viral pathogens., Highlights • An optimized differentiation protocol improves maturation of intestinal organoids • SARS-CoV-2 and SARS-CoV infection triggers less robust response than enteroviruses • Coronaviruses show lower sensitivity to type III IFNs than enteroviruses • Intestinal organoids recapitulate disparate pathogenicity of CoVs and enteroviruses, Zhao and colleagues modified the composition of differentiation medium and demonstrated that the optimized medium improves the maturation state of human intestinal organoids. Two coronaviruses, SARS-CoV-2 and SARS-CoV, and two enteroviruses, EV-A71 and CVA16, reveal distinct profiles of virus-host interaction in the optimized intestinal organoids. Overall, human intestinal organoids adequately recapitulate disparate pathogenicity of coronaviruses and enteroviruses in the human intestines.

BackgroundSevere acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is an emerging coronavirus that has resulted in more than 2 000 000 laboratory-confirmed cases including over 145 000 deaths. Although SARS-CoV-2 and SARS-CoV share a number of common clinical manifestations, SARS-CoV-2 appears to be highly efficient in person-to-person transmission and frequently causes asymptomatic or presymptomatic infections. However, the underlying mechanisms that confer these viral characteristics of high transmissibility and asymptomatic infection remain incompletely understood.MethodsWe comprehensively investigated the replication, cell tropism, and immune activation profile of SARS-CoV-2 infection in human lung tissues with SARS-CoV included as a comparison.ResultsSARS-CoV-2 infected and replicated in human lung tissues more efficiently than SARS-CoV. Within the 48-hour interval, SARS-CoV-2 generated 3.20-fold more infectious virus particles than did SARS-CoV from the infected lung tissues (P < .024). SARS-CoV-2 and SARS-CoV were similar in cell tropism, with both targeting types I and II pneumocytes and alveolar macrophages. Importantly, despite the more efficient virus replication, SARS-CoV-2 did not significantly induce types I, II, or III interferons in the infected human lung tissues. In addition, while SARS-CoV infection upregulated the expression of 11 out of 13 (84.62%) representative proinflammatory cytokines/chemokines, SARS-CoV-2 infection only upregulated 5 of these 13 (38.46%) key inflammatory mediators despite replicating more efficiently.ConclusionsOur study provides the first quantitative data on the comparative replication capacity and immune activation profile of SARS-CoV-2 and SARS-CoV infection in human lung tissues. Our results provide important insights into the pathogenesis, high transmissibility, and asymptomatic infection of SARS-CoV-2.

Aim This study reviewed the experience of a tertiary paediatric surgery and obstetric centre on prenatal counselling of congenital surgical anomalies and to explore the role of paediatric surgeons on perinatal outcomes of antenatally detected anomalies. Methods A retrospective analysis of all antenatal consultations and subsequent medical records after birth were performed between 2009 and 2018. Data including timing of consultations, gestations at birth, birthweight, impact on obstetrics management, neonatal mortality and need of surgery were included. Results A total of 256 fetuses were diagnosed to have congenital surgical anomalies on antenatal ultrasound. The most common were urogenital (31%) and thoracic (30%) anomalies. Twelve of the 256 (4.7%) had multiple anomalies. The mean gestation at referral was 23 ± 5 weeks. The majority (85.4%) were born at term. Mode and timing of delivery was altered in 7% of patients. Four received fetal intervention after surgical consultation. Termination of pregnancy rate was 5.4% (n = 14). Neonatal death was reported in 7.8% of the cohort. Conclusion Congenital surgical anomalies had a significant impact on perinatal outcome as well as morbidity in later infancy and childhood. A multidisciplinary approach in managing pregnancy with these anomalies should be implemented. Combined-specialty consultations and counselling deliver valuable information for parents.

Background And Aims Besides prominent respiratory involvement, gastrointestinal manifestations are commonly reported in Coronavirus Disease 2019 (COVID-19) patients. We compared infection of ex vivo human intestinal tissues by SARS-CoV-2 and SARS-CoV with respect to their replication kinetics and immune activation profile. Methods Human intestinal tissues were obtained from patients while undergoing surgical operations at the Queen Mary Hospital, Hong Kong. Upon surgical removal, the tissues were immediately processed and infected with SARS-CoV-2 or SARS-CoV. Replication kinetics were determined with immunohistochemistry, qRT-PCR, and plaque assays. Immune activation in the infected intestinal tissues was assessed by detecting the gene expression of interferons and representative pro-inflammatory cytokines and chemokines. Results SARS-CoV-2 could infect and productively replicate in the ex vivo human intestinal tissues with the release of infectious virus particles, but not in ex vivo human liver and kidney tissues. Importantly, SARS-CoV-2 replicated less efficiently than SARS-CoV, induced less cytopathology in the human intestinal epithelium, and induced a more robust innate immune response including the activation of both type I and type III interferons, than SARS-CoV in human intestinal tissues. Conclusion Using the ex vivo human intestinal tissues as a physiologically relevant model, our data indicated that SARS-CoV-2 could productively replicate in the human guts, suggesting the gastrointestinal tract might serve as an alternative route of virus dissemination. SARS-CoV-2 replicated less efficiently and induced less cytopathology than SARS-CoV in keeping with the clinical observations reported for SARS-2003 and COVID-19, which might be a result of the more robust immune activation by SARS-CoV-2 than SARS-CoV in the human intestine., SARS-CoV-2 induces a higher innate immune response while replicates less efficiently and induces less cytopathology than SARS-CoV in the human intestinal tissues. These findings potentially explained the differential gastrointestinal manifestations observed in COVID-19 and SARS-2003.

SARS-CoV-2 is more infectious and transmissible in humans than SARS-CoV, despite the genetic relatedness and sharing the same cellular receptor. We sought to assess whether human airway organoids can model SARS-CoV-2 infection in the human airway and elucidate the cellular basis underlying its higher transmissibility. We demonstrate that SARS-CoV-2 can establish a productive infection in human airway organoids, in which ciliated cell and basal cell are infected. Wildtype SARS-CoV-2 carrying a furin cleavage motif exhibits comparable replication kinetics to a mutant virus without the motif. Human airway organoids sustain higher replication of SARS-CoV-2 than SARS-CoV, whereas interferon response is more potently induced in the latter than the former. Overall, human airway organoids can model SARS-CoV-2 infection and recapitulate the disposable role of furin cleavage motif for virus transmission in humans. SARS-CoV-2 stealth growth and evasion of interferon response may underlie pre-symptomatic virus shedding in COVID-19 patients, leading to its high infectiousness and transmissibility.

SARS-CoV-2 has affected over 9 million patients with more than 460,000 deaths in about 6 months. Understanding the factors that contribute to efficient SARS-CoV-2 infection of human cells, which are not previously reported, may provide insights on SARS-CoV-2 transmissibility and pathogenesis, and reveal targets of intervention. Here, we reported key host and viral determinants that were essential for efficient SARS-CoV-2 infection in the human lung. First, we identified heparan sulfate as an important attachment factor for SARS-CoV-2 infection. Second, we demonstrated that while cell surface sialic acids significantly restricted SARS-CoV infection, SARS-CoV-2 could largely overcome sialic acid-mediated restriction in both human lung epithelial cells and ex vivo human lung tissue explants. Third, we demonstrated that the inserted furin-like cleavage site in SARS-CoV-2 spike was required for efficient virus replication in human lung but not intestine tissues. Overall, these findings contributed to our understanding on efficient SARS-CoV-2 infection of human lungs.

Understanding the factors that contribute to efficient SARS-CoV-2 infection of human cells may provide insights on SARS-CoV-2 transmissibility and pathogenesis, and reveal targets of intervention. Here, we analyze host and viral determinants essential for efficient SARS-CoV-2 infection in both human lung epithelial cells and ex vivo human lung tissues. We identify heparan sulfate as an important attachment factor for SARS-CoV-2 infection. Next, we show that sialic acids present on ACE2 prevent efficient spike/ACE2-interaction. While SARS-CoV infection is substantially limited by the sialic acid-mediated restriction in both human lung epithelial cells and ex vivo human lung tissues, infection by SARS-CoV-2 is limited to a lesser extent. We further demonstrate that the furin-like cleavage site in SARS-CoV-2 spike is required for efficient virus replication in human lung but not intestinal tissues. These findings provide insights on the efficient SARS-CoV-2 infection of human lungs., Here, using lung epithelial cells and ex vivo tissue explants, the authors show that, in addition to ACE2, host heparan sulfate is directly involved in SARS-CoV-2 attachment and entry and provide data suggesting that host sialic acids may act as viral restriction factor in lung tissues.

A novel coronavirus-severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-emerged in humans in Wuhan, China, in December 2019 and has since disseminated globally1,2. As of April 16, 2020, the confirmed case count of coronavirus disease 2019 (COVID-19) had surpassed 2 million. Based on full-genome sequence analysis, SARS-CoV-2 shows high homology to SARS-related coronaviruses identified in horseshoe bats1,2. Here we show the establishment and characterization of expandable intestinal organoids derived from horseshoe bats of the Rhinolophus sinicus species that can recapitulate bat intestinal epithelium. These bat enteroids are fully susceptible to SARS-CoV-2 infection and sustain robust viral replication. Development of gastrointestinal symptoms in some patients with COVID-19 and detection of viral RNA in fecal specimens suggest that SARS-CoV-2 might cause enteric, in addition to respiratory, infection3,4. Here we demonstrate active replication of SARS-CoV-2 in human intestinal organoids and isolation of infectious virus from the stool specimen of a patient with diarrheal COVID-19. Collectively, we established the first expandable organoid culture system of bat intestinal epithelium and present evidence that SARS-CoV-2 can infect bat intestinal cells. The robust SARS-CoV-2 replication in human intestinal organoids suggests that the human intestinal tract might be a transmission route of SARS-CoV-2.

A novel coronavirus-severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-emerged in humans in Wuhan, China, in December 2019 and has since disseminated globally

Aim We investigated the efficacy of endoscopic-Deflux-injection in treating primary-vesicoureteric-reflux (VUR) and identified factors to predict resolution. Materials and methods Records of children treated with Deflux for primary-VUR from 1995 to 2016 were reviewed, and outcomes were investigated. Results Eighty-eight ureters (35 bilateral, 18 unilateral) in 53 children underwent 124 injections. Thirty-five (66%) patients had single injection (13 unilateral, 22 bilateral). Fifteen (28%), two (37%), and one (2%) patients had two, three, and four injections, respectively. Overall success rate by ureters was 57% after single injection. Complete resolution occurred in 65% of ureters with VUR below grade III, 63% of grade III, 40% of grade IV, and 70% of grade V VUR. Four patients had reimplantation. The median follow up duration was 60 months (range 20–216 months). Univariate analysis showed that lower VUR grade (p = 0.03) and absent renal scars (p = 0.04) were statistically significant predictors of resolution. In multivariate analysis, absent renal scars were statistically significant (p = 0.01). Conclusion We demonstrated efficacy of endoscopic-Deflux-injection as the first line treatment for primary-VUR. Absent renal scar and lower VUR grade were statistically significant predictors of resolution after single injection. Type of study Case–Control / Retrospective Comparative Study. Level of evidence Level III.

Pediatric inguinal hernia is one of the most common surgical conditions with open herniotomy being the gold standard of treatment. With the advances of laparoscopic surgery, it has emerged as an alternative to open repair with reported good results. However, laparoscopic hernia repair is not yet a routine procedure in many centers, and debate of laparoscopic versus open repair still exists. After 20 years of development of laparoscopic hernia repair, different techniques have been described with no consensus on the standard technique right now. This article reviews the latest updates of laparoscopic repair from the current evidence in the literature. Laparoscopic management of hernia in premature/small infants and hernia incarceration are also discussed here.

Summary Paediatric urological surgery is often required for managing congenital and acquired disorders of the genitourinary system. In this Series paper, we highlight advances in the surgical management of six paediatric urological disorders. The management of vesicoureteral reflux is evolving, with advocacy ranging from a less interventional assessment and antimicrobial prophylaxis to surgery including endoscopic injection of a bulking agent and minimally invasive ureteric reimplantation. Evidence supports early orchidopexy to improve fertility and reduce malignancy in boys with undescended testes. A variety of surgical techniques have been developed for hypospadias, with excellent outcomes for distal but not proximal hypospadias. Pelvi-ureteric junction obstruction is mostly detected prenatally; indications for surgery have been refined with evidence, and minimally invasive pyeloplasty is now standard. The outlook for patients with neurogenic bladder has been transformed by a combination of clean intermittent catheterisation, algorithms of diagnostic investigations, and innovative medical and surgical therapies. Posterior urethral valves are associated with considerable mortality; fetal diagnosis allows stratification of candidates for intervention, but ongoing bladder dysfunction in patients after valve ablation remains a cause of long-term morbidity.

Viruses are obligate intracellular microbes that exploit the host metabolic machineries to meet their biosynthetic demands, making these host pathways potential therapeutic targets. Here, by exploring a lipid library, we show that AM580, a retinoid derivative and RAR-α agonist, is highly potent in interrupting the life cycle of diverse viruses including Middle East respiratory syndrome coronavirus and influenza A virus. Using click chemistry, the overexpressed sterol regulatory element binding protein (SREBP) is shown to interact with AM580, which accounts for its broad-spectrum antiviral activity. Mechanistic studies pinpoint multiple SREBP proteolytic processes and SREBP-regulated lipid biosynthesis pathways, including the downstream viral protein palmitoylation and double-membrane vesicles formation, that are indispensable for virus replication. Collectively, our study identifies a basic lipogenic transactivation event with broad relevance to human viral infections and represents SREBP as a potential target for the development of broad-spectrum antiviral strategies., Viruses rely on host cell metabolism for replication, making these pathways potential therapeutic targets. Here, the authors show that AM580, a retinoid derivative and RAR-α agonist, affects replication of several RNA viruses by interfering with the activity of SREBP.

Human intestinal tract as an alternative route to acquire MERS-CoV infection., Middle East respiratory syndrome coronavirus (MERS-CoV) has caused human respiratory infections with a high case fatality rate since 2012. However, the mode of virus transmission is not well understood. The findings of epidemiological and virological studies prompted us to hypothesize that the human gastrointestinal tract could serve as an alternative route to acquire MERS-CoV infection. We demonstrated that human primary intestinal epithelial cells, small intestine explants, and intestinal organoids were highly susceptible to MERS-CoV and can sustain robust viral replication. We also identified the evidence of enteric MERS-CoV infection in the stool specimen of a clinical patient. MERS-CoV was considerably resistant to fed-state gastrointestinal fluids but less tolerant to highly acidic fasted-state gastric fluid. In polarized Caco-2 cells cultured in Transwell inserts, apical MERS-CoV inoculation was more effective in establishing infection than basolateral inoculation. Notably, direct intragastric inoculation of MERS-CoV caused a lethal infection in human DPP4 transgenic mice. Histological examination revealed MERS-CoV enteric infection in all inoculated mice, as shown by the presence of virus-positive cells, progressive inflammation, and epithelial degeneration in small intestines, which were exaggerated in the mice pretreated with the proton pump inhibitor pantoprazole. With the progression of the enteric infection, inflammation, virus-positive cells, and live viruses emerged in the lung tissues, indicating the development of sequential respiratory infection. Taken together, these data suggest that the human intestinal tract may serve as an alternative infection route for MERS-CoV.

Middle East respiratory syndrome (MERS) is associated with a mortality rate of >35%. We previously showed that MERS coronavirus (MERS-CoV) could infect human macrophages and dendritic cells and induce cytokine dysregulation. Here, we further investigated the interplay between human primary T cells and MERS-CoV in disease pathogenesis. Importantly, our results suggested that MERS-CoV efficiently infected T cells from the peripheral blood and from human lymphoid organs, including the spleen and the tonsil. We further demonstrated that MERS-CoV infection induced apoptosis in T cells, which involved the activation of both the extrinsic and intrinsic apoptosis pathways. Remarkably, immunostaining of spleen sections from MERS-CoV-infected common marmosets demonstrated the presence of viral nucleoprotein in their CD3(+) T cells. Overall, our results suggested that the unusual capacity of MERS-CoV to infect T cells and induce apoptosis might partly contribute to the high pathogenicity of the virus.

Background & Aims Biliary atresia (BA) is a rare and most severe cholestatic disease in neonates, but the pathogenic mechanisms are unknown. Through a previous genome wide association study (GWAS) on Han Chinese, we discovered association of the 10q24.2 region encompassing ADD3 and XPNPEP1 genes, which was replicated in Chinese and Thai populations. This study aims to fully characterize the genetic architecture at 10q24.2 and to reveal the link between the genetic variants and BA. Methods We genotyped 107 single nucleotide polymorphisms (SNPs) in 10q24.2 in 339 Han Chinese patients and 401 matched controls using Sequenom. Exhaustive follow-up studies of the association signals were performed. Results The combined BA-association p -value of the GWAS SNP (rs17095355) achieved 6.06×10 −10 . Further, we revealed the common risk haplotype encompassing 5 tagging-SNPs, capturing the risk-predisposing alleles in 10q24.2 [ p =5.32×10 −11 ; odds ratio, OR: 2.38; confidence interval, CI: (2.14-2.62)]. Through Sanger sequencing, no deleterious rare variants (RVs) residing in the risk haplotype were found, dismissing the theory of "synthetic" association. Moreover, in bioinformatics and in vivo genotype-expression investigations, the BA-associated potentially regulatory SNPs correlated with ADD3 gene expression (n=36; p =0.0030). Remarkably, the risk haplotype frequency coincides with BA incidences in the population, and, positive selection (favoring the derived alleles that arose from mutations) was evident at the ADD3 locus, suggesting a possible role for the BA-associated common variants in shaping the general population diversity. Conclusions Common genetic variants in 10q24.2 can alter BA risk by regulating ADD3 expression levels in the liver, and may exert an effect on disease epidemiology and on the general population.

Background With advances in minimally invasive surgery, thoracoscopic repair of oesophageal atresia has become popular in many centres worldwide and indeed has been described as the pinnacle of neonatal surgery. Here, we report our experience in two tertiary referral centres. Methods Thoracoscopic technique was introduced in 2007. Thus, a retrospective review of all patients diagnosed with oesophageal atresia was carried out. Patients who had thoracoscopic repair were included, and those who had open repair due to co-morbidities were excluded. Patient demographics, operative data, complications, and associated anomalies were noted. Results A total of thirty-three patients underwent thoracoscopic repair during the time period. Thirty-one were successfully repaired thoracoscopically. Two patients had conversions due to intra-operative instability. The mean body weight of the neonates was 2.58kg. The mean operative time was 146min. Three patients suffered from minor anastomotic leaks, which healed on conservative management. Seven patients had anastomotic strictures, which responded successfully to endoscopic dilatation. Two patients died in the post-operative period due to pneumonia. One patient had a recurrent fistula 3months after the primary repair, and he subsequently underwent a successful second repair. Conclusions In experienced hands, thoracoscopic repair of oesophageal atresia is at least as good as open surgery but with less surgical trauma. Standard of post-operative care contributes significantly to post-operative outcome. Thoracoscopic technique is now our preferred approach.

PURPOSE: Laparoendoscopic single-site surgery has recently been described in children and regarded as an improved technology leading to less pain and better cosmetic outcome. Compared to the traditional three-port method, it is not known if the single-port method is less invasive. The aim of this study was thus to investigate the post-operative acute inflammatory response in order to evaluate surgical stress in the two surgical approaches in children. METHODS: A prospective, single blinded, case-control study was carried out. Thirteen male patients who presented with unilateral varicocele were divided into two groups. Six children underwent single-port laparoscopic procedure, while the other seven children underwent three-port laparoscopic procedure. Pre-operative and post-operative blood samples were taken for the measurement of tumor necrosis factor-alpha (TNF-alpha) and interleukin 6 (IL-6) using ELISA. Demographics including the operation time, and complications were recorded. Data between the two groups were analyzed using unpaired t-test and a p value of, published_or_final_version, Springer Open Choice, 21 Feb 2012

This report is of robotic-assisted laparoscopic Mitrofanoff appendicovesicostomy in a 12-year-old patient with detrusor underactivity and hereditary sensory neuropathy. The whole operation was performed in 555 minutes with no open conversion. The patient experienced one episode of stomal stenosis, which required dilatation. At 3-year follow-up, the patient had both stomal and urinary continence. This is a safe and effective procedure to create a means of urinary catheterisation with avoidance of a large unsightly scar and comparable clinical outcome to an open procedure.

Objectives To review all paediatric patients with intussusception over the last 17 years. Design Retrospective case series. Setting A tertiary centre in Hong Kong. Patients Children who presented with intussusception from January 1997 to December 2014 were reviewed. Main outcome measures The duration of symptoms, successful treatment modalities, complication rate, and length of hospital stay were studied. Results A total of 173 children (108 male, 65 female) presented to our hospital with intussusception during the study period. Their median age at presentation was 12.5 months (range, 2 months to 16 years) and the mean duration of symptoms was 2.3 (standard deviation, 1.8) days. Vomiting was the most common symptom (76.3%) followed by abdominal pain (46.2%), per rectal bleeding or red currant jelly stool (40.5%), and a palpable abdominal mass (39.3%). Overall, 160 patients proceeded to pneumatic or hydrostatic reduction, among whom 127 (79.4%) were successful. Three (1.9%) patients had bowel perforation during the procedure. Early recurrence of intussusception occurred in four (3.1%) patients with non-operative reduction. No recurrence was reported in the operative group. The presence of a palpable abdominal mass was a risk factor for operative treatment (relative risk=2.0; 95% confidence interval, 1.8-2.2). Analysis of our results suggested that duration of symptoms did not affect the success rate of non-operative reduction. Conclusions Non-operative reduction has a high success rate and low complication rate, but the presence of a palpable abdominal mass is a risk factor for failure. Operative intervention should not be delayed in those patients who encounter difficult or doubtful non-operative reduction.

Anorectal malformations (ARMs, congenital obstruction of the anal opening) are among the most common birth defects requiring surgical treatment (2-5/10 000 live-births) and carry significant chronic morbidity. ARMs present either as isolated or as part of the phenotypic spectrum of some chromosomal abnormalities or monogenic syndromes. The etiology is unknown. To assess the genetic contribution to ARMs, we investigated single-nucleotide polymorphisms and copy number variations (CNVs) at genome-wide scale. A total of 363 Han Chinese sporadic ARM patients and 4006 Han Chinese controls were included. Overall, we detected a 1.3-fold significant excess of rare CNVs in patients. Stratification of patients by presence/absence of other congenital anomalies showed that while syndromic ARM patients carried significantly longer rare duplications than controls (P = 0.049), non-syndromic patients were enriched with both rare deletions and duplications when compared with controls (P = 0.00031). Twelve chromosomal aberrations and 114 rare CNVs were observed in patients but not in 868 controls nor 11 943 healthy individuals from the Database of Genomic Variants. Importantly, these aberrations were observed in isolated ARM patients. Gene-based analysis revealed 79 genes interfered by CNVs in patients only. In particular, we identified a de novo DKK4 duplication. DKK4 is a member of the WNT signaling pathway which is involved in the development of the anorectal region. In mice, Wnt disruption results in ARMs. Our data suggest a role for rare CNVs not only in syndromic but also in isolated ARM patients and provide a list of plausible candidate genes for the disorder.

Background Laparoscopic anorectoplasty was introduced in 2000, but the procedure has not yet gained universal acceptance. Previous studies, including ours, reported satisfactory early postoperative outcome as compared with posterior sagittal anorectoplasty (PSARP), but mid- to long-term results are not available. Here, we aim to evaluate the mid- to long-term defecative function in these patients. Materials and Methods A retrospective study was carried out and included all patients who underwent laparoscopic-assisted anorectoplasty for high-/intermediate-type imperforate anus between 2001 and 2005. Their degree of continence was graded according to the Krickenbeck classification and compared with historical controls treated with PSARP. The results were compared using χ 2 test, and P Results There were 18 patients who underwent laparoscopic anorectoplasty (LAR) in the study period. They were compared with 20 historical PSARP patients. For defecation sensation, 16 of the 18 LAR patients were positive, whereas there were 16 of 20 PSARP patients. Eight LAR patients were clean without any fecal soiling or incontinence (11/20 PSARP). Only 3 of 18 LAR had constipation as compared with 7 of 20 PSARP. The need for rectal enema for evacuation was seen in 1 of 20 LAR patients and 2 of 20 PSARP patients (for all categories, P > .05). Conclusions Mid- to long-term follow-up study revealed satisfactory defecative function for patients with high-/intermediate-type imperforate anus after LAR. The outcome is at least as good as PSARP. Longer term follow-up with larger sample size is necessary to demonstrate the benefits of LAR over PSARP.

Hirschsprung disease (HSCR, congenital colon aganglionosis) is a relatively common complex genetic condition caused by abnormal development of the enteric nervous system (ENS). Through a recent genome-wide association study conducted on Chinese HSCR patients, we identified a new HSCR contributing locus, neuregulin 1 (NRG1; 8p12), a gene known to be involved in the development of the ENS. As genes in which disease-associated common variants are found are to be considered as candidates for the search of deleterious rare variants (RVs) in the coding sequences, we sequenced the NRG1 exons of 358 sporadic HSCR patients and 333 controls. We identified a total of 13 different heterozygous RVs including 8 non-synonymous (A28G, E134K, V266L, H347Y, P356L, V486M, A511T, P608A) and 3 synonymous amino acid substitutions (P24P, T169T, L483L), a frameshift (E239fsX10), and a c.503-4insT insertion. Functional analysis of the most conserved non-synonymous substitutions, H347Y and P356L, showed uneven intracellular distribution and aberrant expression of the mutant proteins. Except for T169T and V486M, all variants were exclusive to HSCR patients. Overall, there was a statistically significant over-representation of NRG1 RVs in HSCR patients (p = 0.008). We show here that not only common, but also rare variants of the NRG1 gene contribute to HSCR. This strengthens the role of NRG1.

The introduction of Kasai portoenterostomy has dramatically improved the management and survival of children with biliary atresia. The success rate of this operation worldwide varies with different centers. In this respect, many authors have studied the correlation of a successful outcome with various factors, such as the experience and workload of the surgical center, the use of postoperative steroids, the underlying biliary anatomy, as well as the age of patients at the time of the operation. Indeed, the age of 60 days has been used by clinicians as a critical time beyond which the rate of success of the Kasai operation markedly reduces. Despite this worldwide adoption, clear evidence supporting this critical operative time is still lacking. We undertook a review of our experience in the management of children with biliary atresia and focused specifically on the issue of the timing of operation. We showed that performing the Kasai operation beyond the age of 60 days was not associated with a worse outcome and that a high percentage of patients could still achieve good bile flow with normal bilirubin postoperatively. Thus, we believe that until the age of 100 days, the age of the patients does not play a significant role in determining the success of the Kasai operation.

Rare (RVs) and common variants of the RET gene contribute to Hirschsprung disease (HSCR; congenital aganglionosis). While RET common variants are strongly associated with the commonest manifestation of the disease (males; short-segment aganglionosis; sporadic), rare coding sequence (CDS) variants are more frequently found in the lesser common and more severe forms of the disease (females; long/total colonic aganglionosis; familial). Here we present the screening for RVs in the RET CDS and intron/exon boundaries of 601 Chinese HSCR patients, the largest number of patients ever reported. We identified 61 different heterozygous RVs (50 novel) distributed among 100 patients (16.64%). Those include 14 silent, 29 missense, 5 nonsense, 4 frame-shifts, and one in-frame amino-acid deletion in the CDS, two splice-site deletions, 4 nucleotide substitutions and a 22-bp deletion in the intron/exon boundaries and 1 single-nucleotide substitution in the 5′ untranslated region. Exonic variants were mainly clustered in RET the extracellular domain. RET RVs were more frequent among patients with the most severe phenotype (24% vs. 15% in short-HSCR). Phasing RVs with the RET HSCR-associated haplotype suggests that RVs do not underlie the undisputable association of RET common variants with HSCR. None of the variants were found in 250 Chinese controls. © 2011 So et al., published_or_final_version