Bazedoxifene Suppresses the Growth of Osteosarcoma Cells by Inhibiting IL-6 and IL-11/GP130 Signaling Pathway.

Osteosarcoma is the most common primary bone tumor. Using the multiple ligands simultaneous docking method, we found that bazedoxifene could bind to the GP130 D1 domain. We then demonstrated that bazedoxifene can decrease cell viability and cell migration of osteosarcoma cells by inhibiting interleukin 6 (IL-6) and IL-11/GP130 signaling. Consistently, treatment with IL-6 or IL-11 antibody or knockdown of GP130 by siRNA silenced the activation of STAT3, ERK, and AKT. Similarly, recombinant IL-6 and IL-11 proteins antagonized the inhibitory effect of bazedoxifene on osteosarcoma cells. Finally, the combinational treatment of temsirolimus and bazedoxifene synergistically suppressed osteosarcoma development in vitro and in vivo. Our findings suggest that bazedoxifene directly prompts the deactivation of GP130 and inhibits the osteosarcoma progression in vitro and in vivo. Therefore, bazedoxifene could be effectively applied as a therapeutic drug for human osteosarcoma in the future.

Cinchophen induces RPA1 related DNA damage and apoptosis to impair ENS development of zebrafish.

Nonsteroidal anti-inflammatory drugs (NSAIDs) have become contaminants widely distributed in the environment due to improper disposal and discharge. Previous study has found several components might involve in impairing enteric nervous system (ENS) development of zebrafish, including NSAIDs cinchophen. Deficient ENS development in fetal could lead to Hirschsprung disease (HSCR), a congenital neurocristopathy characterized by absence of enteric neurons in hindgut. However, the intrinsic mechanism of neurotoxicity of cinchophen is unclear. We confirmed that cinchophen could impair ENS development of zebrafish and transcriptome sequencing revealed that disfunction of Replication protein A1 (RPA1), which is involved in DNA replication and repairment, might be relevant to the neurotoxicity effects induced by cinchophen. Based on previous data of single cell RNA sequencing (scRNA-seq) of zebrafish gut cells, we observed that rpa1 mainly expressed in proliferating, differentiating ENS cells and neural crest progenitors. Interestingly, cinchophen induced apoptosis and impaired proliferation. Furthermore, cinchophen caused DNA damage and abnormal activation of ataxia telangiectasia mutated/ Rad3 related (ATM/ATR) and checkpoint kinase 2 (CHK2). Finally, molecular docking indicated cinchophen could bind and antagonize RPA1 more effectively. Our study might provide a better understanding and draw more attention to the role of environmental factors in the pathogenesis of HSCR. And the mechanism of cinchophen neurotoxicity would give theoretical guidance for clinical pharmacy.

Identification of autophagy-related gene and lncRNA signatures in the prognosis of HNSCC.

OBJECTIVE: The aim of this study was to identify prognostic autophagy-related genes and lncRNAs to predict clinical outcomes in head and neck squamous cell carcinoma (HNSCC). SUBJECTS AND METHODS: Differentially expressed autophagy-related genes and autophagy-related lncRNAs were identified by comparing pare-carcinoma and carcinoma samples of HNSCC. And then, we constructed an ARG and an AR-lncRNA signature risk score. Receiver operating characteristic (ROC) curve analyses were performed to assess the prognostic prediction capacity. Gene Set Enrichment Analysis (GSEA) and Gene Ontology (GO) functional annotation were used to analysis the functions of ARGs and AR-lncRNAs. RESULTS: Six ARGs and thirteen AR-lncRNAs were identified in the ARG and AR-lncRNA signatures, and overall survival (OS) in the high-risk group was significantly shorter than the low-risk group. ROC analysis showed the ARG and AR-lncRNA signatures have excellent ability of predicting the total OS of patients with HNSCC. What's more, GSEA and GO functional annotation proved that autophagy-related pathways are mainly enriched in the high-risk group. CONCLUSIONS: These findings indicated that our ARG signature and AR-lncRNA signature could be considered to predict the prognosis of patients with HNSCC and provide a deep understanding of the biological mechanisms of autophagy in HNSCC.

Abnormally elevated expression of ACTA2 of circular smooth muscle leads to hyperactive contraction in aganglionic segments of HSCR.

BACKGROUND: Actin Alpha 2 (ACTA2) is expressed in intestinal smooth muscle cells (iSMCs) and is associated with contractility. Hirschsprung disease (HSCR), one of the most common digested tract malformations, shows peristaltic dysfunction and spasm smooth muscles. The arrangement of the circular and longitudinal smooth muscle (SM) of the aganglionic segments is disorganized. Does ACTA2, as a marker of iSMCs, exhibit abnormal expression in aganglionic segments? Does the ACTA2 expression level affect the contraction function of iSMCs? What are the spatiotemporal expression trends of ACTA2 during different developmental stages of the colon? METHODS: Immunohistochemical staining was used to detect the expression of ACTA2 in iSMCs of children with HSCR and Ednrb-/- mice, and the small interfering RNAs (siRNAs) knockdown technique was employed to investigate how Acta2 affected the systolic function of iSMCs. Additionally, Ednrb-/- mice were used to explore the changes in the expression level of iSMCs ACTA2 at different developmental stages. RESULTS: The expression of ACTA2 is higher in circular SM in the aganglionic segments of HSCR patients and Ednrb-/- mice than in normal control children and mice. Down regulation of Acta2 weakens the contraction ability of intestinal smooth muscle cells. Abnormally elevated expression of ACTA2 of circular smooth muscle occurs since embryonic day 15.5 (E15.5d) in aganglionic segments of Ednrb-/- mice. CONCLUSIONS: Abnormally elevated expression of ACTA2 in the circular SM leads to hyperactive contraction, which may cause the spasm of aganglionic segments in HSCR.

Inflammatory Myofibroblastic Tumor of the Sigmoid Colon in an Infant: A Case Report and Literature Review.

Inflammatory myofibroblastic tumor (IMT) infrequently involves the sigmoid colon, and has not previously been described in an infant sigmoid colon.An inflammatory myofibroblastic tumor arose from the sigmoid colon of an 11-month-old boy, confirmed by anaplastic lymphoma kinase (ALK), smooth muscle actin (SMA) and desmin immunohistochemical staining. The patient recovered well after complete resection of the tumor.Sigmoid IMT can occur in infancy. This eighth case is the youngest so far. The child did well after surgical resection.

Transanal full-thickness pull-through approach in the treatment of anastomotic leakage after operation for Hirschsprung disease.

BACKGROUND: Anastomotic leakage (AL) is one of the most perplexing complications that can occur following a radical operation to treat Hirschsprung disease (HSCR). The purpose of this study was to document our experience with anastomotic leakage following radical HSCR surgery to enhance therapeutic effect and prognosis. METHODS: Between January 2007 and April 2021, a retrospective study was conducted on 12 children who developed anastomotic leakage following radical surgery for HSCR. Medical records were analyzed to determine the clinical manifestations, primary surgical procedures, evaluation methods, surgical plans, and outcomes of the patients. To assess postoperative bowel function, the Rintala score was used. RESULTS: The Soave procedure was used as the primary surgical method in seven cases (58.3%), the Swenson procedure was used in four cases (33.3%), and the Rehbein procedure was used in one case (8.3%). Enterostomy (10, 83.3%) and conservative treatment (2, 16.7%) were performed when anastomotic leakage was diagnosed. Two patients who directly closed stoma without redoing pull-through both accepted enterostomy within 48 h. One female with anastomotic fistula who was closed leakage or fistula in situ had to endure lifelong stoma. Other patients who underwent redo pull-through procedures had normal bowel function. Seven patients underwent a redo pull-through procedure. Three of them preferred the transanal full-thickness pull-through (FTPT) approach, while four preferred the Soave technique. Three children had mild postoperative soiling, which improved with conservative treatment. Bowel function score was 17.5 ± 1.1. CONCLUSION: Enterostomy should be performed immediately if anastomotic leakage occurs. After leakage, it is necessary to redo the pull-through procedure in an anastomotic fistula or anastomotic stricture. Transanal FTPT reconstruction is an effective method for repairing anastomoses and leakage.

Down-Regulation of Double C2 Domain Alpha Promotes the Formation of Hyperplastic Nerve Fibers in Aganglionic Segments of Hirschsprung's Disease.

Hirschsprung's disease (HSCR) is a common developmental anomaly of the gastrointestinal tract in children. The most significant characteristics of aganglionic segments in HSCR are hyperplastic extrinsic nerve fibers and the absence of endogenous ganglion plexus. Double C2 domain alpha (DOC2A) is mainly located in the nucleus and is involved in Ca2+-dependent neurotransmitter release. The loss function of DOC2A influences postsynaptic protein synthesis, dendrite morphology, postsynaptic receptor density and synaptic plasticity. It is still unknown why hyperplastic extrinsic nerve fibers grow into aganglionic segments in HSCR. We detected the expression of DOC2A in HSCR aganglionic segment colons and established three DOC2A-knockdown models in the Neuro-2a cell line, neural spheres and zebrafish separately. First, we detected the protein and mRNA expression of DOC2A and found that DOC2A was negatively correlated with AChE+ grades. Second, in the Neuro-2a cell lines, we found that the amount of neurite outgrowth and mean area per cell were significantly increased, which suggested that the inhibition of DOC2A promotes nerve fiber formation and the neuron's polarity. In the neural spheres, we found that the DOC2A knockdown was manifested by a more obvious connection of nerve fibers in neural spheres. Then, we knocked down Doc2a in zebrafish and found that the down-regulation of Doc2a accelerates the formation of hyperplastic nerve fibers in aganglionic segments in zebrafish. Finally, we detected the expression of MUNC13-2 (UNC13B), which was obviously up-regulated in Grade3/4 (lower DOC2A expression) compared with Grade1/2 (higher DOC2A expression) in the circular muscle layer and longitudinal muscle layer. The expression of UNC13B was up-regulated with the knocking down of DOC2A, and there were protein interactions between DOC2A and UNC13B. The down-regulation of DOC2A may be an important factor leading to hyperplastic nerve fibers in aganglionic segments of HSCR. UNC13B seems to be a downstream molecule to DOC2A, which may participate in the spasm of aganglionic segments of HSCR patient colons.

NOX1/4 Inhibitor GKT-137831 Improves Erectile Function in Diabetic Rats by ROS Reduction and Endothelial Nitric Oxide Synthase Reconstitution.

BACKGROUND: Previous studies have shown that oxidative stress contributes to hyperglycemia-induced erectile dysfunction. A preferential direct inhibitor of NOX1 and NOX4, GKT-137831, exhibited a strong anti­oxidative role via blockade of reactive oxygen species (ROS) generation in endothelial cells, but whether GKT-137831 could improve erectile function was not clear. AIM: Our study was designed to investigate the effect of NOX1/4 inhibition on improving diabetic erectile dysfunction (ED) in rats. METHODS: We used streptozotocin to induce type 1 diabetes mellitus (DM) in 32 male Sprague Dawley (SD) rats (8 weeks old). Eight weeks later, type 1 diabetes mellitus-induced erectile dysfunction (DMED) in rats was confirmed using an apomorphine test. Our study consisted of 3 groups: (i) nondiabetic control group (n = 8), (ii) DMED + vehicle group (DMED group; n = 8), and (iii) DMED + GKT-137831 group (n = 9); GKT-137831 was given as a once-daily intraperitoneal injection for 4 weeks. Cavernous nerve electrostimulation was used to evaluate erectile function. Western blot, ELISA, immunohistochemistry, and immunofluorescence were used to measure expression of specific proteins, and DHE fluorescent probe was performed to detect ROS level. OUTCOMES: Intracavernous pressure (ICP), nitric oxide (NO)/cyclic guanosine monophosphate (cGMP) signaling pathway, oxidative stress level, inflammatory response, corporal autophagy, and apoptosis were measured. RESULTS: Erectile function in the DMED group was significantly impaired compared to the nondiabetic control group, whereas this impairment was improved with GKT-137831 treatment by 70%. Similarly, endothelial function and overactivated oxidative stress in the corpus cavernosum (CC) of the DMED + GKT-137831 group were improved. The DMED group showed serious inflammatory responses and excessive autophagy, which were inhibited by GKT-137831 treatment in the DMED + GKT-137831 group. CLINICAL TRANSLATION: Our study showed improvement in erectile function with GKT-137831 in a diabetic rat ED model. STRENGTH AND LIMITATIONS: This study suggested for the first time that GKT-137831, an NOX1/4 inhibitor undergoing clinical trials, is effective in improving erectile function in rats with type 1 DMED. However, we only investigated GKT-137831 treatment of streptozotocin-induced type 1 diabetic rats, and therapeutic evidence in other types of diabetes is lacking. CONCLUSION: GKT-137831 improves erectile function by 70% in type 1 DMED rats and constitutes a promising compound for the treatment of type 1 DMED, likely by inhibition of overactivated oxidative stress, down-regulation of proinflammatory factors, and amelioration of excessive autophagy and endothelial function. B Zhou, Y Chen, H Yuan, et al. NOX1/4 Inhibitor GKT-137831 Improves Erectile Function in Diabetic Rats by ROS Reduction and Endothelial Nitric Oxide Synthase Reconstitution. J Sex Med 2021;18:1970-1983.

Activated M1 macrophages suppress c-kit expression via TNF-α-mediated upregulation of miR-222 in Neonatal Necrotizing Enterocolitis.

BACKGROUND: Activation of intestinal macrophages is implicated in the pathogenesis of neonatal necrotizing enterocolitis (NEC), yet its precise mechanisms remain unclear. OBJECTIVE: The purpose of this study is to investigate the role of macrophages and TNF-α via an inflammatory MicroRNA in NEC. MATERIALS AND METHODS: Immunofluorescence (IF) staining of CD68, iNOS, and Arg-1 was employed to identify phenotypes of macrophage in the intestines of NEC infants and NEC mice. Expression of TNF-α, c-kit, and miR-222 was evaluated by qRT-PCR, Western blot, and immunochemical staining from the tissue samples. RESULTS: Large number of M1 macrophage infiltration was found in the NEC intestines. Expression of CD68, iNOS, and TNF-α were significantly increased, while c-kit was decreased distinctly in the NEC group. In the early phase of NEC mouse model, inhibition of M1 macrophages reduced the incidence of NEC and intestinal inflammation. We found that TNF-α upregulated the expression of miRNA-222 and inhibited the expression of c-kit. Conversely, such decrease of c-kit expression could be reversed by miR-222 antagonists. Furtherly, dual-luciferase assay confirmed that c-kit can be inhibited by miR-222 directly. CONCLUSION: Macrophages activation in NEC intestine results in an increased inflammatory response and TNF-α production, accompanied with miR-222 upregulation and c-kit suppression. Modulations of M1 macrophages, TNF-α or miR-222 may be potential therapeutic targets for NEC treatment.

NOX5 is expressed aberrantly but not a critical pathogenetic gene in Hirschsprung disease.

BACKGROUND: Hirschsprung disease (HSCR) is a congenital disorder characterized by the absence of intramural ganglion cells in the distal gastrointestinal tract (GI), which results in tonic contraction of the aganglionic gut segment and functional intestinal obstruction. Recent studies have suggested NADPH oxidase 5 (NOX5) as a candidate risk gene for HSCR. In this study, we examined the function of NOX5 to verify its role in the development of the enteric nervous system (ENS). METHODS: HSCR tissue specimens (n = 10) were collected at the time of pull-through surgery and control specimens (n = 10) were obtained at the time of colostomy closure in patients. The NOX5 expression in aganglionic and ganglionic segments of HSCR colon and normal colon were analyzed by immunohistochemistry (IHC), western blot and real-time quantitative PCR (qPCR). The gene expression levels and spatiotemporal expression spectrum of NOX5 in different development stages of zebrafish embryo were determined using qPCR and in-situ hybridization (ISH). The enteric nervous system in NOX5 Morpholino (MO) knockdown and wild type (WT) zebrafish embryo was analyzed by whole-mount immunofluorescence (IF). Intestinal transit assay was performed to analyze the gastrointestinal motility in NOX5 knockdown and control larvae. RESULTS: NOX5 is strongly expressed in the ganglion cells in the proximal segment of HSCR colons and all segments of normal colons. Moreover, the expression of NOX5 is markedly decreased in the aganglionic segment of HSCR colon compared to the ganglionic segment. In zebrafish, NOX5 mRNA level is the highest in the one cell stage embryos and it is decreased overtime with the development of the embryos. Interestingly, the expression of NOX5 appears to be enriched in the nervous system. However, the number of neurons in the GI tract and the GI motility were not affected upon NOX5 knockdown. CONCLUSIONS: Our study shows that NOX5 markedly decreased in the aganglionic segment of HSCR but didn't involve in the ENS development of zebrafish. It implies that absence of intestinal ganglion cells may lead to down-regulation of NOX5.

Combined analysis of RNA-sequence and microarray data reveals effective metabolism-based prognostic signature for neuroblastoma.

The relationship between metabolism reprogramming and neuroblastoma (NB) is largely unknown. In this study, one RNA-sequence data set (n = 153) was used as discovery cohort and two microarray data sets (n = 498 and n = 223) were used as validation cohorts. Differentially expressed metabolic genes were identified by comparing stage 4s and stage 4 NBs. Twelve metabolic genes were selected by LASSO regression analysis and integrated into the prognostic signature. The metabolic gene signature successfully stratifies NB patients into two risk groups and performs well in predicting survival of NB patients. The prognostic value of the metabolic gene signature is also independent with other clinical risk factors. Nine metabolism-related long non-coding RNAs (lncRNAs) were also identified and integrated into the metabolism-related lncRNA signature. The lncRNA signature also performs well in predicting survival of NB patients. These results suggest that the metabolic signatures have the potential to be used for risk stratification of NB. Gene set enrichment analysis (GSEA) reveals that multiple metabolic processes (including oxidative phosphorylation and tricarboxylic acid cycle, both of which are emerging targets for cancer therapy) are enriched in the high-risk NB group, and no metabolic process is enriched in the low-risk NB group. This result indicates that metabolism reprogramming is associated with the progression of NB and targeting certain metabolic pathways might be a promising therapy for NB.

A Morphology-based Analysis of Biliary Ductules After Kasai Procedure and a Review of the Literature.

OBJECTIVE: To explore the distribution of biliary ductules in biliary remnants of patients with biliary atresia and to investigate the relationship between the ductules and the prognosis after Kasai portoenterostomy. PATIENTS AND METHODS: From October 01, 2015 to September 30, 2017, 46 patients who were diagnosed as type 3 biliary atresia were enrolled in this study. Continuous sections of biliary remnants were stained with cytokerantin 19 antibody. The number, area, and distribution of micro-biliary ductules of each section were recorded. According to the number of ductules in the most proximal section (n ≥ 20 or n < 20), patients were divided into two groups (A or B) and followed up for 1-3 y, including cholangitis, jaundice clearance, and survival with native liver. RESULTS: Four patients had no micro-biliary ductules. In 17 patients with ductules, the numbers at bilateral parts were similar (P > 0.05), while the ductules in the middle part were significantly less than bilateral parts (P < 0.05). Starting from 2 mm from the proximal end of remnants, the number of ductules significantly and gradually decreased (P < 0.05). The total area of ductules in Group A was significantly increased compared to that in Group B (P < 0.05). Patients in Group A had significantly higher jaundice clearance rate and better survival rate with native liver than patients in Group B (both, P < 0.05). Patients had significantly higher incidence of cholangitis in Group A compared to Group B (P < 0.05). CONCLUSIONS: The number/area of ductules yielded by technical precision is closely related to effective bile drainage, jaundice clearance, and first onset of cholangitis in patients after Kasai procedure.

Long-term outcomes of single-incision laparoscopic technique in Soave procedure compared with heart-shaped anastomosis for Hirschsprung disease.

PURPOSE: This retrospective study compared the long-term outcomes of single-incision laparoscopy-assisted Soave procedure (SILSP) with single-incision laparoscopy-assisted heart-shaped anastomosis (SILHSA) in patients with Hirschsprung disease (HSCR). METHODS: Patients diagnosed with HSCR that underwent SILSP or SILHSA between January 2009 and January 2015 at our institute were enrolled in this retrospective study. Data on the clinical characteristics, perioperative complications, and postoperative quality of life were retrospectively collected and analyzed. RESULTS: There were 109 patients in the SILSP group and 95 patients in the SILHSA group. No differences in clinical characteristics, including age, weight, hospitalization length, blood loss volume, and operation time, were noted between the two groups. The incidence rates of constipation and soiling were lower in the SILHSA group than those in the SILSP group. The SILHSA group showed lower scores in constipation and soiling compared with the SILSP group, indicating a better surgical outcome for patients receiving SILHSA procedure. CONCLUSION: SILHSA is a feasible and reliable minimally invasive surgical procedure for patients with HSCR. Patients who underwent SILHSA had lower incidence rates of constipation and soiling than patients who underwent SILSP, suggesting that SILHSA could be a better choice for patients with HSCR.

Dual roles of commensal bacteria after intestinal ischemia and reperfusion.

PURPOSE: The roles of commensal bacteria after intestinal ischemia and reperfusion (IIR) are unclear. In current study, we aim to investigate the effects and underlying mechanisms of commensal bacteria in injury and epithelial restitution after IIR. METHODS: Commensal gut bacteria were deleted by broad-spectrum antibiotics in mice. IIR was induced by clamping superior mesenteric artery. Intestinal injury, permeability, epithelial proliferation, and proinflammatory activity of mesenteric lymph were investigated. RESULTS: Commensals deletion improved mice survival in the early phase, but failed to improve the overall survival at 96 h after IIR. Commensals deletion reduced proliferation of intestinal epithelial cells (IEC) and augmented proinflammatory activity of mesenteric lymph after IIR. Lipopolysaccharides (LPS) supplement promoted IEC proliferation and improved survival in mice with commensals deletion after IIR. LPS induced production of prostaglandin E2 (PGE2) in mucosa via toll-like receptor 4-NFκB-cyclooxygenase 2 pathway. PGE2 enhanced IEC proliferation in vivo, which was preceded by activation of Akt and extracellular signal-regulated kinase (ERK) 1/2. Blocking of EGFR, PI3K/Akt activity abolished LPS-induced IEC proliferation. CONCLUSIONS: Commensal bacteria are essential for epithelial restitution after IIR, which enhance IEC proliferation via induction of PGE2.

Biliary atresia in twins'population: a retrospective multicenter study in mainland China.

AIM: We evaluated the demographic of biliary atresia (BA) children from twins family and aimed to investigated what it can add to the twins' literature and our understanding of the disease. METHODS: This study contains 11 medical centers in mainland China and the medical record of twins with BA was retrospectively analyzed from January 2012 to December 2018. Follow-up was carried out by out-patient review and questionnaire. RESULTS: The study included 19 twin pairs in whom there was discordance for BA. Sixteen (84.2%) affected twin underwent Kasai Procedure (KP); median age at KP was 78 (49-168) days. There were ten affected twins that became jaundice-free at 3 months post-KP, and eight occurred with different degrees of cholangitis post-KP. Six affected twins received Liver Transplantation (LT) successfully. The 2 year native liver survival rate and the 2 year overall survival rate of affected twins were 61.1 and 94.4%, respectively. There were three affected monozygotic (MZ) twins and one healthy co-twin with BA-associated congenital malformations, all of which were cardiac malformations. The number of virus infection of affected MZ twins was significantly more (p = 0.04) than affected dizygotic (DZ) twin. CONCLUSIONS: Discordance for BA in 19 pairs of twins supported that BA may be related to genetic phenotype or penetrance. The difference in genetic background between MZ and DZ affects the susceptibility of the host to virus infection. High acceptance of KP (84.2%) in our study implied a high motivation for treatment for twins with BA. Delays of KP (78 days) in affected twin may be related to the postnatal gradual onset and the late diagnosis.

Optimal time for single-stage pull-through colectomy in infants with short-segment Hirschsprung disease.

OBJECTIVE: Short-segment Hirschsprung disease (HSCR) is the predominant type of HSCR that affects approximately 75% of patients. Whether single-stage endorectal pull-through (ERPT) surgery is appropriate for neonatal patients with HSCR has not been definitively determined. This retrospective cohort study concerning infants with short-segment HSCR investigated the optimal age for single-stage ERPT surgery, regardless of the operative approach. METHODS: The 198 patients were stratified by operative age ≤ 3 or > 3 months (groups A or B, respectively, n = 62 and 136, respectively). Diagnoses of short-segment HSCR were conducted by preoperative contrast enema and rectal suction biopsy with acetylcholinesterase immunohistochemical staining. The perioperative clinical course for all patients was reviewed and the accuracy rate of the preoperative diagnoses and postoperative short- and midterm outcomes were assessed. RESULTS: The rates of diagnostic accuracy, according to the results of the preoperative contrast enema or rectal suction biopsy, were lower in group A (67.2 and 93.5%, respectively) than in group B (81.4 and 94.9%, respectively). In groups A and B, 49 (79.1%) and 108 (79.4%) infants, respectively, completed follow-up examinations. The short-term outcomes were postoperative HSCR-associated enterocolitis, adhesive bowel obstruction, anastomosis leakage, and anal stenosis during the first 12 months after surgery. The midterm outcomes were incontinence and constipation at ~24 months after surgery. Compared with group B, group A experienced more incidences of anastomotic leakage in the short-term and more soiling in the midterm. In groups A and B, the rates of constipation recurrence were nil and 1.9%, respectively. CONCLUSION: Infants with HSCR ≤3 months old at the time of single-stage ERPT surgery showed lower rates of accurate and conclusive diagnostic results and poorer postoperative outcomes. Waiting to perform this surgery until infants are older might be more beneficial.

Results of rectoanal manometry after a novel laparoscopic technique: laparoscope-assisted heart-shaped anastomosis for Hirschsprung's disease.

PURPOSE: The present research utilizes a mid-term follow-up study to assess the results of anorectal manometry after laparoscope-assisted heart-shaped anastomosis (LHSA) for Hirschsprung's disease (HSCR), and compares it to a more generally applied approach, the laparoscope-assisted Soave procedure (LSP). METHODS: Retrospectively, patients from January 2015 to June 2017 who received LHSA or LSP were included in this study. After surgery, anorectal manometry was performed by the outpatient department. Anal sphincter resting pressure, anal canal length, amplitude of anal contraction, and frequency of anal contraction pre- and postoperatively were recorded. Additionally, mid-term complications were also monitored. RESULTS: Preoperative manometry showed no statistically significant difference between the LHSA and LSP groups. Postoperatively, anal sphincter resting pressure was lower in the LHSA group (60.64 ± 9.33 vs. 68.84 ± 11.80 mmHg, p = 0.001). Furthermore, anal canal length of the LHSA group was shorter than that of the LSP group (1.41 ± 0.18 vs. 1.53 ± 0.25 cm, p = 0.015). Frequency of anal contraction also showed a statistically significant difference between the LHSA and LSP groups (13.53 ± 2.17 vs. 12.50 ± 2.03 per minute, p = 0.032). The complication rates showed no significant difference and were as follows: incidence of enterocolitis was 13.89% in the LHSA group and 20.45% in the LSP group, incidence of constipation was 11.11% after LHSA and 27.27% after LSP, and incidence of soiling was 13.89% after LHSA and 25.00% after LSP. CONCLUSIONS: Manometric results of this study show satisfactory outcomes after LHSA. LHSA is an advanced surgical technique to make intestinal anastomosis easy and ensure a good prognosis.

A retrospective study of the ideal operation time for preterm biliary atresia patients.

OBJECTIVE: To study the ideal Kasai portoenterostomy (KPE) time for preterm infants with biliary atresia (BA) through evaluation of the postoperative effects. METHODS: Retrospectively, 34 preterm infants with BA from 2012 to 2016 were recruited in the present study. The following three groups were established according to their chronological and corrected age at the time of KPE operation: chronological age ≤ 90 days, chronological age > 90 days and corrected age ≤ 90 days, and corrected age > 90 days. For chronological age ≤ 90 days at operation, patients were further divided into another three groups: chronological age ≤ 60 days, chronological age > 60 days and corrected age ≤ 60 days, and corrected age > 60 days. Postoperative effects were then followed up and recorded. RESULTS: First, of those patients divided according to 90-day chronological and corrected age, postoperative total bilirubin levels (TBL), direct bilirubin levels (DBL), alanine aminotransferase (ALT), and aspartate aminotransferase (AST) of the group whose chronological age was ≤ 90 days were lower than the levels of the group whose chronological age was > 90 days and corrected age ≤ 90 days (P = 0.0472, P = 0.0358, P = 0.0083, and P = 0.0491), and the group whose corrected age was > 90 days (P = 0.0383, P = 0.0392, P = 0.0043, and P = 0.0107). Second, for those patients whose chronological age was ≤ 90 days, the group whose corrected age was > 60 days showed a higher ALT level than the other two groups with chronological age ≤ 60 days (P = 0.0472) and chronological age > 60 days and corrected age ≤ 60 days (P = 0.0258). CONCLUSION: According to the present study, the ideal KPE time for preterm BA infants should meet two conditions: chronological age ≤ 90 days and corrected age ≤ 60 days. The groups with a chronological age ≤ 60 days, and chronological age > 60 days and corrected age ≤ 60 days show similar postoperative effects.

Kasai procedure improves nutritional status and decreases transplantation-associated complications.

BACKGROUND: The aim of this study was to retrospectively investigate whether Kasai Procedure (KP) improves nutritional status and whether KP decreases liver transplantation (LT)-associated complications in children with biliary atresia (BA). METHODS: From March 1st 2014 to February 28th 2015, 103 patients underwent LT and the other 17 without prior KP died during the waiting period. In 103 patients undergoing LT, 58 patients received KP previously (Group A), and 45 only underwent primary LT (Group B). The nutritional status, liver function and LT-related short-term complications were analyzed. RESULTS: Compared to Group B, patients in Group A had significantly increased time interval when undergoing LT (p < 0.05). Persistently, the bodyweight, albumin and hemoglobin in Group A were significantly increased compared to Group B (all, p < 0.0001). The bilirubin, ALT/AST and PELD score in Group A were all decreased compared to Group B (p < 0.05) prior to LT. The incidences of post-LT severe infection and hypoalbuminemia in Group A were significantly lower than those of Group B (p < 0.05). CONCLUSIONS: KP improves the nutritional status, preserves liver function for patients who finally undergo LT, and decreases the incidence post-LT severe infection and hypoalbuminemia. Mental health can be improved in parents whose children underwent previous KP.

Intravenous immunoglobulin for the treatment of intractable cholangitis after Kasai portoenterostomy in biliary atresia patients.

OBJECTIVE: To assess the efficacy of intravenous immunoglobulin (IVIG) as add-on treatment for intractable cholangitis (IC) after Kasai portoenterostomy (KPE) in biliary atresia (BA) patients. METHODS: 113 BA patients who had one or more episodes of cholangitis after KPE were recruited in this study. According to whether response to routine conservative treatment, all patients were divided into IC group and simple cholangitis (SC) group. Meanwhile, patients with IC subdivided into IVIG group and control group according to whether application of IVIG. RESULTS: The IC group had higher serum procalcitonin (PCT) (P = 0.014), C-reactive protein (CRP) (P = 0.023), and γ-Gltamyltranspeptidase (γ-GGT) (P = 0.031) level than the SC group. The IVIG group had shorter duration of fever after treatment (P = 0.011) and length of hospital stay (P = 0.018) than the control group. The time until recurrent episode of cholangitis was significant longer in IVIG group than in control group (P = 0.019). CONCLUSIONS: IVIG as add-on treatment may be an effective treatment for the cholangitis acute episode, and we conclude by calling for more prospective studies to attest to the role of IVIG in the treatment of cholangitis.