Clinical characteristics of postoperative necrotizing enterocolitis in patients with congenital jejunoileal atresia and its risk factors.

Objective: To review postoperative necrotizing enterocolitis (NEC) in patients with jejunoileal atresia (JIA) and to explore the potential risk factors related to the concurrence of NEC. Methods: Patients diagnosed with JIA who received surgical treatment from January 2016 to June 2021 were enrolled. Demographics, viral infection of the fetus, transfusion within 48 hours before NEC, sepsis before JIA repair, pathological and anatomical classification of JIA, combined malformation, occurrence time of NEC after the operation, treatment, and prognosis of patients were analyzed. Patients were divided into NEC group and non-NEC group, and all patients were followed up for 3-6 months to observe for complications. Results: A total of 180 patients with JIA were included, of whom 12 were diagnosed with NEC after surgery and 1 patient with NEC died during follow-up. The average age, birth weight, gestational age, proportion of premature infants, proportion of preoperative infections, and pathological classification of JIA did not significantly differ between the two groups. The probability of patients with proximal jejunal atresia (PJA) in the NEC group (58.3%) was higher than that in the non-NEC group (22.6%) (p=0.011), and patients with PJA had longer parenteral nutrition time than patients without PJA (26.64±9.21 days vs 15.11±6.58 days, p<0.001). Conclusion: PJA was more likely to be associated with concurrent NEC after surgery, which is a highly NEC-related risk factor inherent in JIA.

Mesenchymal Stem Cells Attenuates Hirschsprung Disease-Associated Enterocolitis by Reducing M1 Macrophages Infiltration via COX-2 Dependewhant Mechanism.

OBJECTIVE AND DESIGN: Hirschsprung disease-associated enterocolitis (HAEC) is a common life-threatening complication of Hirschsprung disease (HSCR). We aimed to investigate the effectiveness, long-term safety and the underlying mechanisms of Mesenchymal stem cells (MSCs) based therapy for HAEC. MATERIAL OR SUBJECTS: Specimens from HSCR and HAEC patients were used to assess the inflammatory condition. Ednrb knock-out mice was used as HAEC model. MSCs was intraperitoneally transplanted into HAEC mice. The therapy effects, long-term outcome, safety and toxicity and the mechanism of MSCs on the treatment of HAEC were explored in vivo and in vitro. RESULTS: Intestinal M1 macrophages infiltration and severe inflammation condition were observed in HAEC. After the injection of MSCs, HAEC mice showed significant amelioration of the inflammatory injury and inhibition of M1 macrophages infiltration. The expression levels of pro-inflammatory cytokines (TNF-α and IFN-γ) were decreased and anti-inflammatory cytokines (IL-10 and TGF-ß) were increased. In addition, we found that effective MSCs homing to the inflamed colon tissue occurred without long-term toxicity response. However, COX-2 inhibitor could diminish the therapeutic effects of MSCs. Using MSCs and macrophages co-culture system, we identified that MSCs could alleviate HAEC by inhibiting M1 macrophages activation through COX-2-dependent MAPK/ERK signaling pathway. CONCLUSIONS: MSCs ameliorate HAEC by reducing M1 macrophages polarization via COX-2 mediated MAPK/ERK signaling pathway, thus providing novel insights and potentially promising strategy for the treatment or prevention of HAEC.

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.

Nomogram for soiling prediction in postsurgery hirschsprung children: a retrospective study.

PURPOSE: The aim of this study was to develop a nomogram for predicting the probability of postoperative soiling in patients aged greater than 1 year operated for Hirschsprung disease (HSCR). MATERIALS AND METHODS: The authors retrospectively analyzed HSCR patients with surgical therapy over 1 year of age from January 2000 and December 2019 at our department. Eligible patients were randomly categorized into the training and validation set at a ratio of 7:3. By integrating the least absolute shrinkage and selection operator [LASSO] and multivariable logistic regression analysis, crucial variables were determined for establishment of the nomogram. And, the performance of nomogram was evaluated by C-index, area under the receiver operating characteristic curve, calibration curves, and decision curve analysis. Meanwhile, a validation set was used to further assess the model. RESULTS: This study enrolled 601 cases, and 97 patients suffered from soiling. Three risk factors, including surgical history, length of removed bowel, and surgical procedures were identified as predictive factors for soiling occurrence. The C-index was 0.871 (95% CI: 0.821-0.921) in the training set and 0.878 (95% CI: 0.811-0.945) in the validation set, respectively. And, the AUC was found to be 0.896 (95% CI: 0.855-0.929) in the training set and 0.866 (95% CI: 0.767-0.920) in the validation set. Additionally, the calibration curves displayed a favorable agreement between the nomogram model and actual observations. The decision curve analysis revealed that employing the nomogram to predict the risk of soiling occurrence would be advantageous if the threshold was between 1 and 73% in the training set and 3-69% in the validation set. CONCLUSION: This study represents the first efforts to develop and validate a model capable of predicting the postoperative risk of soiling in patients aged greater than 1 year operated for HSCR. This model may assist clinicians in determining the individual risk of soiling subsequent to HSCR surgery, aiding in personalized patient care and management.

Severity assessment to guide empiric antibiotic therapy for cholangitis in children after Kasai portoenterostomy: a multicenter prospective randomized control trial in China.

BACKGROUND: Cholangitis is common in patients with biliary atresia following Kasai portoenterostomy (KPE). The prompt use of empiric antibiotics is essential due to the lack of identified microorganisms. The authors aimed to validate a severity grading system to guide empiric antibiotic therapy in the management of post-KPE cholangitis. MATERIALS AND METHODS: This multicenter, prospective, randomized, open-label study recruited patients with post-KPE cholangitis and was conducted from January 2018 to December 2019. On admission, patients were categorized into mild, moderate, and severe cholangitis according to the severity grading system. Patients in the mild cholangitis group were randomized to receive cefoperazone sodium tazobactam sodium (CSTS) or meropenem (MEPM). Patients with severe cholangitis were randomized to treatment with MEPM or a combination of MEPM plus immunoglobulin (MEPM+IVIG). Patients with moderate cholangitis received MEPM. RESULTS: The primary endpoint was duration of fever (DOF). Secondary outcomes included blood culture, length of hospital stay, incidence of recurrent cholangitis, jaundice clearance rate, and native liver survival (NLS). For mild cholangitis, DOF, and length of hospital stay were similar between those treated with CSTS or MEPM (all P >0.05). In addition, no significant difference in recurrence rate, jaundice clearance rate, and NLS was observed between patients treated with CSTS and MEPM at 1-month, 3-month, and 6-month follow-up. In patients with moderate cholangitis, the DOF was 36.00 (interquartile range: 24.00-48.00) h. In severe cholangitis, compared with MEPM, MEPM+IVIG decreased DOF and improved liver function by reducing alanine aminotransferase, aspartate aminotransferase, gamma-glutamyl transferase, and direct bilirubin at 1-month follow-up. However, recurrence rate, jaundice clearance rate, and NLS did not differ significantly between MEPM+IVIG and MEPM at 1-month, 3-month, and 6-month follow-up. CONCLUSIONS: In patients with post-KPE cholangitis, MEPM is not superior to CSTS for the treatment of mild cholangitis. However, MEPM+IVIG treatment was associated with better short-term clinical outcomes in patients with severe cholangitis.

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.

Comprehensive characterization of the genetic landscape of familial Hirschsprung's disease.

BACKGROUND: Hirschsprung's disease (HSCR) is one of the most common congenital digestive tract malformations and can cause stubborn constipation or gastrointestinal obstruction after birth, causing great physical and mental pain to patients and their families. Studies have shown that more than 20 genes are involved in HSCR, and most cases of HSCR are sporadic. However, the overall rate of familial recurrence in 4331 cases of HSCR is about 7.6%. Furthermore, familial HSCR patients show incomplete dominance. We still do not know the penetrance and genetic characteristics of these known risk genes due to the rarity of HSCR families. METHODS: To find published references, we used the title/abstract terms "Hirschsprung" and "familial" in the PubMed database and the MeSH terms "Hirschsprung" and "familial" in Web of Science. Finally, we summarized 129 HSCR families over the last 40 years. RESULTS: The male-to-female ratio and the percentage of short segment-HSCR in familial HSCR are much lower than in sporadic HSCR. The primary gene factors in the syndromic families are ret proto-oncogene (RET) and endothelin B receptor gene (EDNRB). Most families show incomplete dominance and are relevant to RET, and the RET mutation has 56% penetrance in familial HSCR. When one of the parents is a RET mutation carrier in an HSCR family, the offspring's recurrence risk is 28%, and the incidence of the offspring does not depend on whether the parent suffers from HSCR. CONCLUSION: Our findings will help HSCR patients obtain better genetic counseling, calculate the risk of recurrence, and provide new insights for future pedigree studies.

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.

Screening of undernutrition in children with Hirschsprung disease using preoperative anthropometric parameters: A multicenter cross-sectional study.

BACKGROUND: The prevalence of malnutrition is unknown in patients with Hirschsprung disease. Undernutrition is associated with poor clinical outcomes. This study aims to describe the nutrition status among patients with Hirschsprung disease at admission. METHODS: We retrospectively used data from children with Hirschsprung disease admitted to three pediatric surgery centers in China from January 2016 to December 2020. The weight-for-age z scores (WAZ), height-for-age z scores (HAZ), and body mass index-for-age z scores (BAZ) were calculated as the reference for nutrition risk according to the World Health Organization child growth standards. The nutrition status of enrolled children was described and nutrition risk in each clinical characteristic was compared. The association between nutrition status and clinical outcomes was analyzed using univariate and multivariate logistic regression. RESULTS: A total of 624 patients were included in this study. The mean WAZ, HAZ, and BAZ of all patients was -0.64 ± 1.40, -0.45 ± 1.78, and -0.43 ± 1.50, respectively. Moderate to severe overall undernutrition was 16.3% (102/624). We found that WAZ and BAZ were significantly reduced with the length of aganglionic segments (P = 0.001). Children who had a definitive surgery at 3 years of age or older had significantly lower HAZ (P = 0.001). A multivariate regression model assessing postoperative Hirschsprung-associated enterocolitis showed that the WAZ was one of the independent risk factors (P = 0.001). CONCLUSION: Undernutrition is prevalent among children with Hirschsprung disease. Nutrition assessment to identify individuals at risk of undernutrition for further intervention is necessary.

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.

Role of cholinergic innervation in biliary remnants of patients with biliary atresia.

Objective: Biliary innervation is considered important in regulating the function of bile ducts, whereas the role of innervation in the hepatobiliary system of patients with biliary atresia (BA) remains unknown. This current study aims to investigate the role of innervation in biliary remnants and analyze the relationship between the innervation and prognosis of BA after surgery. Methods: Eighty-seven patients with type III BA who underwent the Kasai procedure were consecutively enrolled from January 2017 to September 2020. Innervation and ductules in remnants were examined by pathologists. Liver function, onset of cholangitis, jaundice clearance, and survival with the native liver were recorded. Patients were followed up for 24 months. The relationship between innervation and prognosis was analyzed. Results: In total, 67 patients had bile drainage postoperatively, and 21 biliary remnants contained neuronal plexuses where there was no neuron but nerve fiber bundles. Acetylcholinesterase staining was positive in all plexuses. In patients with bile drainage, those with plexuses had improved postoperative liver function, significantly better jaundice clearance 3 or 6 months postoperatively (50.0% vs. 19.1%, or 90.0% vs. 63.8%, respectively), fewer episodes of early cholangitis (10.0% vs. 34.0%), and better survival (80.0% vs. 61.7%) compared to those without. In addition, a larger area of plexuses was associated with a larger area of ductules (R2 = 0.786, p = 0.000), less frequent (p = 0.000) and later cholangitis onset (p = 0.012), and better jaundice clearance (p = 0.063). Conclusions: Increased cholinergic innervation in biliary remnants may help reduce the onset of cholangitis and lead to better and earlier jaundice clearance. Thus, it improves the postoperative prognosis of patients with BA.

An autophagy-related four-lncRNA signature helps to predict progression-free survival of neuroblastoma patients.

Background: This study aimed to identify autophagy-related long non-coding RNAs (lncRNAs) associated with progression of neuroblastoma (NB), and to build an autophagy-related lncRNA signature that helps to predict progression-free survival (PFS) of NB. Methods: Three independent gene expression datasets were utilized in this study. Autophagy-related genes (ARG) associated with PFS of NB patients were firstly identified by univariate Cox survival analysis. lncRNAs correlated with those PFS-related ARGs were then identified. The least absolute shrinkage and selection operator (LASSO) regression and multivariate Cox regression analyses were performed to select out those lncRNAs with the best prognostic value for PFS. The Receiver Operating Characteristic (ROC) and Area Under Curve (AUC) analyses were performed to assess the prediction accuracy. Results: Four autophagy-related lncRNAs (AL356599.1, AC022075.1, AC020928.1 and LINC02076) were found to be with the best prognostic value and integrated into a four-lncRNA risk signature for predicting PFS of NB patients. The four-lncRNA signature significantly stratify NB patients into two risk groups, with high-risk group has significantly poorer PFS than the low-risk group. The prognostic role of the lncRNA signature was independent with other clinical risk factors. The ROC curves revealed that the lncRNA signature has a good performance in predicting PFS (AUC > 0.70). A nomogram based on COG (Children's Oncology Group) risk and the lncRNA risk score was constructed, showing good prediction accuracy (C-index = 0.700). The prognostic ability of the nomogram was better than that of COG risk alone (AUC = 0.790 versus AUC = 0.748). GSEA analyses revealed that multiple autophagy-related gene sets are significantly enriched in the low-risk group. Conclusions: We identified an autophagy-related four-lncRNA signature that could help to predict the PFS of NB patients. Autophagy-related gene sets are significantly enriched in low-risk group, suggesting tumor suppressive roles of autophagy in NB.

Treatment of postoperative intestinal dysfunction of hirschsprung's disease based on the principle of "anorectal balance".

Purpose: Radical surgery is the most effective treatment for Hirschsprung's disease. However, some children still have symptoms of intestinal dysfunction such as constipation, abdominal distension, and recurrent enterocolitis after operation. The purpose of this study was to evaluate treatment outcomes of postoperative intestinal dysfunction in children with Hirschsprung's disease by using the principle of "anorectal balance". Methods: The clinical data of postoperative intestinal dysfunction in children with Hirschsprung's disease in the single treatment group from July 2019 to July 2021 were retrospectively analyzed. All the enrolled children underwent botulinum toxin injection (2.5 U/kg); 3 to 6 months later, the injection was performed again; the children who had received more than two botulinum toxin injections underwent the internal sphincter myectomy. Anorectal manometry was performed routinely after operation, and abdominal distension and defecation were recorded. Results: A total of thirty children with postoperative intestinal dysfunction underwent radical surgery for Hirschsprung's disease were included in this study. Symptoms of constipation, abdominal distension and enterocolitis were improved after botulinum toxin injections in most children compared to before surgery (P < 0.01). After re-injection of botulinum toxin in twelve children, the frequency of defecation increased, the anal resting pressure decreased, and the clinical symptoms were relieved again (P < 0.05). Eleven children underwent internal sphincter myectomy, and the symptoms of constipation, abdominal distension and enterocolitis were significantly improved after the operation (P < 0.01). Conclusion: Botulinum toxin injection and internal sphincter myectomy based on the principle of "anorectal balance" can effectively reduce the resting pressure of the anus and relieve intestinal dysfunction, and have satisfactory clinical effect.

The utility of the 24-h delayed film of barium enema for detecting the dysganglionic bowel segment in Hirschsprung's disease.

Background: Preoperative evaluation of the dysganglionic bowel segment is critical for establishing the optimal resection strategy for Hirschsprung's disease (HSCR), which facilitates patient outcomes. Objective: We set out to determine the utility of the 24-h delayed film of barium retention in predicting the length of dysganglionic bowel segment in HSCR. Materials and methods: A retrospective study of patients with clinically suspicious HSCR who underwent a preoperative 24-h delayed film of barium enema and were surgically treated from January 2015 to December 2019 was conducted. Results: Two hundred and 58 patients were enrolled in this study. The sensitivity, specificity, positive and negative predictive values (NPVs) of the 24-h delayed film of barium enema to predict the neuropathological segment were 89.1, 91.5, 91.3, and 89.4%, respectively. The Youden index was 80.6%, with a kappa value of 0.806 (P < 0.001). The correlation rate between barium retention level and pathological results was 72.7% (16/22) when aganglionosis was restricted within the mid-distal rectum (short-segment type), increasing to 92.0% (46/50) and 93.5% (174/186) for patients that had aganglionosis extended beyond the mid-distal rectum (classical type) and sigmoid colon (long-segment type), respectively. Lastly, patients younger than 3 months showed a lower correlation rate (72.2%) compared to patients aged 3-12 months (91.0%) and > 12 months (92.6%). Conclusions: Our investigation of the 24-h delayed film of barium enema performed for patients suspected of having HSCR indicated that the barium retention level remains crucial in predicting dysganglionic bowel segment, which contributes to the decision-making for surgical physicians.

Identification and validation of the common pathogenesis and hub biomarkers in Hirschsprung disease complicated with Crohn's disease.

Background: Although increasing evidence has supported that Hirschsprung disease (HSCR) is the risk factor for children developing Crohn's disease (CD), the common mechanism of its co-occurrence remains unknown. The purpose of this study is to further explore the underlying mechanism and biomarkers for the co-occurrence of HSCR and CD. Methods: The Gene Expression Omnibus (GEO) database was used to obtain gene expression profiles for CD (GSE95095) and HSCR (GSE98502). Following the identification of the shared differentially expressed genes (DEGs) of CD and HSCR, functional annotation, protein-protein interaction (PPI) network creation, and module assembly were performed to discover hub genes. RT-qPCR was performed to validate the expression of the hub genes in HSCR samples. The receiver operating characteristic (ROC) curve was utilized to assess the accuracy of the hub genes as biomarkers in predicting CD in both the training dataset and test dataset. Results: A total of 103 common DEGs (50 downregulated genes and 53 upregulated genes) were chosen for further investigation. The importance of chemokines and cytokines in these two disorders is highlighted by functional analysis. MCODE plug identified three important modules, which functionally enriched the immune system process. Finally, nine hub genes were identified using cytoHubba, including IL1B, IL10, CXCL10, ICAM1, EGR1, FCGR3A, S100A12, S100A9, and FPR1. The nine hub genes were mainly enriched in immune- and inflammation-related pathways. External data profiles and RT-qPCR confirmed the expression of the nine hub genes in HSCR and CD. ROC analysis revealed that the nine hub genes had a strong diagnostic value. Conclusion: Our study reveals the common pathogenesis of HSCR and CD. These hub genes and diagnostic models may provide novel insight for the diagnosis and treatment of HSCR complicated with CD.

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.

Anal Canal Duplication Mimicking Recurrent Abscess: A Case Report and Review of the Literature.

Background: Anal canal duplication (ACD) is a very rare duplication of the gastrointestinal tract and is described as a secondary anal orifice along the posterior side of the normal anal canal. Early surgical removal is advisable, also in asymptomatic patients, because of the risk of inflammatory complications, such as recurrent crissum abscess, and malignant changes. Case presentation: A previously healthy 2-year-old boy was evaluated in the emergency department with fever. He complained of anal pain in the absence of incentive. Physical examination and ultrasound confirmed a diagnosis of perianal abscess. He was treated with incision and drainage of the abscess and intravenous antibiotics. Two months after his discharge from the hospital, he developed fever and had intervals discharge pus and pain in the same locations. Colorectal endoscopy revealed that there was no fistula opening at the rectal wall. Intraoperative fistulography showed a fistulous tract that was connected to a subcutaneous cavity. Excision of the fistulous tract and wide drainage of the deep postanal space were performed. The patient was referred to our hospital for further evaluation 6 months later. Physical examination showed a secondary anus that had not been noticed before. MRI showed an anal fistula between 1 and 3 o'clock, and preoperative fistulography revealed a 3-cm-long tubular structure without any connection with the rectum. The diagnosis of ACD was made by intraoperative examination with a metal catheter and the postoperative pathological analysis. The duplicated anal canal was resected completely via a perianal approach without any rectal injury. Histology showed a squamous epithelium in the distal end with some smooth-muscle fibers. After a follow-up of 8 months, the patient has been doing well. Conclusion: Recurrent crissum abscess should raise clinical attention to alimentary tract congenital malformations such as ACD. Prompt recognition of these unique presentations of ACD is needed, and complete excision through a perineal approach or posterior sagittal approach is recommended.

Tumor Microenvironment Profiling Identifies Prognostic Signatures and Suggests Immunotherapeutic Benefits in Neuroblastoma.

The tumor microenvironment (TME) influences disease initiation and progression. Cross-talks of cells within TME can affect the efficacy of immunotherapies. However, a precise, concise, and comprehensive TME landscape in neuroblastoma (NB) has not been established. Here, we profiled the TME landscape of 498 NB-related patients on a self-curated gene list and identified three prognostic TMEsubgroups. The differentially expressed genes in these three TMEsubgroups were used to construct a genetic signature of the TME landscape and characterize three GeneSubgroups. The subgroup with the worst overall survival prognosis, the TMEsubgroup/GeneSubgroup3, lacked immune cell infiltration and received the highest scores of MYCN- and ALK-related signatures and lowest scores of immune pathways. Additionally, we found that the GeneSubgroup3 might be benefited from anti-GD2 instead of anti-PD-1 therapy. We further created a 48-gene signature, the TMEscore, to infer prognosis and validated it in three independent NB cohorts and a pan-cancer cohort of 9,460 patients. We did RNA-seq on 16 samples and verified that TMEscore was higher in patients with stage 3/4 than stage 1/2 diseases. The TMEscore could also predict responses for several immunotherapies. After adding clinical features, we found that the nomogram-based score system, the TMEIndex, surpassed the current risk system at predicting survivals. Our analysis explained TME at the transcriptome level and paved the way for immunotherapies in NB.

Optimal timing for Soave primary pull-through in short-segment Hirschsprung disease: A meta-analysis.

BACKGROUND: The optimal age for endorectal pull-through (ERPT) surgery in infants with short-segment Hirschsprung disease varies, with a trend toward earlier surgery. However, it is unclear if the timing of surgery impacts functional outcomes. We undertook the present study to determine the optimal timing of ERPT in infants with short-segment Hirschsprung disease. METHODS: The NCBI PubMed database was searched for English-language manuscripts published between 2000 and 2019 analyzing functional outcomes for patient following the initial Soave ERPT for short-segment Hirschsprung disease. Raw data from these studies was obtained from the corresponding author for each manuscript. We combined data from these papers with our own institutional data and performed a meta-analysis. RESULTS: A total of 780 infants were included in our meta-analysis. Constipation occurred in 1.0-31.7%, soiling 1.3-26.0%, anastomotic stricture 0.0-14.6%, and anastomotic leak 0.0-3.4%. Regarding age at ERPT, younger infants at the time of initial corrective surgery had higher rates of soiling, stricture, and leak. On sub-group analysis, patients <2.5 months at their initial corrective surgery had higher rates of soiling (25.9% vs. 11.4%, p<0.01), as well as stricture (10.0% vs 1.7%, p<0.01) and leak (5.5% vs 1.3%, p<0.01). CONCLUSION: While age at Soave endorectal pull-through for short-segment Hirschsprung disease has decreased over time, functional outcomes associated with this trend have only recently been examined. Our findings suggest that patients <2.5 months old at the time of endorectal pull-through may have worse functional outcomes, emphasizing the need to consider further study of the timing of surgery in this population.

Diaphyseal and Metaphyseal Modeling Defects-Clinical Findings and Identification of WRAP53 Deficiency in Craniometadiaphyseal Dysplasia.

Background: Diaphyseal and metaphyseal modeling defects lead to severe changes in bone mass and shape, which are common features in osteoporosis that linked to non-vertebral fractures. Original mechanism of diaphyseal and metaphyseal modeling defects has proved elusive. Studying rare syndromes can elucidate mechanisms of common disorders and identify potential therapeutic targets. Methods: We evaluated a family pedigree with craniometadiaphyseal dysplasia (CRMDD, OMIM 269300), a genetic disorder that is characterized by cortical-bone thinning, limb deformity, and absent of normal metaphyseal flaring and diaphyseal constriction. Systemic radiographic examination and serum hormone test were made for this rare disease. One patient and her two normal parents were examined by means of whole-exome sequencing (WES) to identify the candidate pathogenic gene and rule out mucopolysaccharidosis and Prader-Willi Syndrome by means of Sanger sequencing. Results: There are several conspicuous radiographic characteristics: (1) bullet-shaped phalanges, (2) long and narrow pelvic inlet, absent of supra-acetabular constriction, (3) round rod-shaped long tubular bones, (4) prominent aiploic mastoid, (5) bending-shaped limb, genua varus and genu varum, and (6) congenital dislocation of elbow. Here, we did not find any wormian bones, and there are several typical clinical characteristics: (1) macrocephaly and wide jaw, (2) Avatar elf-shaped ears, pointed and protruding ears, (3) hypertrophy of limbs, (4) flat feet and giant hand phenomenon, (5) nail dystrophy, (6) limb deformity, (7) high-arched palate, (8) superficial hemangiomas, (9) tall stature, and intellectual disability. In this patient, we found biallelic frameshift deletion mutations in WRAP53, and those two mutations were transmitted from her parents respectively. Conclusions: We describe her clinical and radiological findings and presented a new subtype without wormian bones and with a tall stature. Our study showed that craniometadiaphyseal dysplasia was caused by a deficiency of WRAP53 with autosomal recessive inheritance.