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To assess the severity of preoperative myopenia and myosteatosis in pediatric patients with inflammatory bowel disease (IBD) and examine their impact on postoperative complications.The subjects of this retrospective study were 30 pediatric patients with IBD (22 with ulcerative colitis (UC) and 8 with Crohn's disease (CD)) and 67 age-matched controls. Preoperative body mass index (BMI), psoas muscle index (PMI), and intramuscular adipose tissue content were compared between the patient groups, to investigate their association with postoperative complications.BMI and PMI were significantly lower in the IBD patients than in the controls (p 0.0001, p 0.0001, respectively). CD was associated with significantly lower BMI and PMI (p = 0.01, p = 0.01, respectively) than UC. Intramuscular adipose tissue content was comparable between the IBD patients and the controls and between the UC and CD patients. There were no significant differences among the three indices in relation to the presence or absence of postoperative complications in patients with IBD. When limited to surgical site infection (SSI), only PMI was significantly lower in the patients with SSI than in those without SSI (p = 0.04).Although BMI and PMI were lower preoperatively in pediatric IBD patients than in controls, only myopenia seemed to affect the development of SSI.

Midgut volvulus is associated with intestinal ischemia/reperfusion (IR) injury and can progress to severe intestinal damage. Remote ischemic conditioning (RIC) reduces IR-induced injury in distant organs. The aim of this study was to investigate whether RIC protects the intestine from IR injury. We investigated intestinal IR injury in 3 weeks old SD rats. Animals underwent: (i) sham laparotomy, (ii) intestinal IR injury, (iii) intestinal IR + RIC during ischemia, or (iv) intestinal IR + RIC after reperfusion. Intestinal IR injury was achieved by 45 min occlusion of superior mesenteric artery followed by de-occlusion. RIC was administered via four cycles of 5 min of hind limb ischemia followed by 5 min reperfusion. Animals were sacrificed 24 h after surgery and the ileum was harvested for evaluation. Intestinal injury was present after IR. However, this injury was reduced in both IR + RIC groups. Expression of inflammatory cytokine IL6 was lower in IR + RIC groups compared to IR alone. Carbonyl protein was also significantly lower in IR + RIC compared to IR, indicating lower oxidative stress in both IR + RIC groups. Remote ischemic conditioning attenuated intestinal injury, inflammation, and oxidative stress in experimental intestinal ischemia/reperfusion injury. Remote ischemic conditioning may be useful in children with midgut volvulus to reduce the intestinal injury. Experimental study. Animal experiment.

Necrotizing enterocolitis (NEC) is a devastating disease of premature infants with high mortality rate, indicating the need for precision treatment. NEC is characterized by intestinal inflammation and ischemia, as well derangements in intestinal microcirculation. Remote ischemic conditioning (RIC) has emerged as a promising tool in protecting distant organs against ischemia-induced damage. However, the effectiveness of RIC against NEC is unknown. To address this gap, we aimed to determine the efficacy and mechanism of action of RIC in experimental NEC. NEC was induced in mouse pups between postnatal day (P) 5 and 9. RIC was applied through intermittent occlusion of hind limb blood flow. RIC, when administered in the early stages of disease progression, decreases intestinal injury and prolongs survival. The mechanism of action of RIC involves increasing intestinal perfusion through vasodilation mediated by nitric oxide and hydrogen sulfide. RIC is a viable and non-invasive treatment strategy for NEC., Necrotizing enterocolitis (NEC) is one of the most lethal gastrointestinal emergencies in neonates needing precision treatment. Here the authors show that remote ischemic conditioning is a non-invasive therapeutic method that enhances blood flow in the intestine, reduces damage, and improves NEC outcome.

Establishment of evidence-based best practices for preventing surgical site infection (SSI) in neonates is needed. SSI in neonates, especially those with a low birth weight, is potentially life-threatening. We aimed to identify risk factors associated with SSI in neonates. A retrospective review was performed using 2007–2016 admission data from our institution. Neonatal patients who were admitted to the neonatal intensive care unit and underwent surgery were evaluated for a relationship between development of SSI and perinatal or perioperative factors and methicillin-resistant Staphylococcus aureus (MRSA) colonization during hospitalization. One hundred and eighty-one patients were enrolled in this study. Overall SSI incidence was 8.8%. Univariate analysis showed that SSI was significantly more frequent in both patients with contaminated or dirty wound operations and patients with MRSA colonization during hospitalization. Both of these factors were identified as independent risk factors for SSI by multivariate analysis [hazard ratio (HR): 6.1, 95% confidence interval (CI) 2.0–19.9; HR: 3.3, 95% CI 1.1–10.4, respectively]. This study identified contaminated or dirty wound operations and MRSA colonization during hospitalization as risk factors for SSI in neonates. MRSA colonization may be a preventable factor, unlike previously reported risk factors.

In neonatal surgical patients requiring an enterostomy, there is no definitive recommendation regarding the ideal enterostomy location: at the edge of the primary incision or at a different incision. We retrospectively reviewed 2005–2017 administration data in our institution. All neonatal patients who underwent contaminated or dirty wound laparotomy and enterostomy construction were evaluated regarding the enterostomy location, occurrence of postoperative incisional surgical-site infection (SSI) at the primary incision, and stoma-related complications. Patients were divided into two groups based on stoma location: at the primary incision (the same incision group: SI group, n = 16) or at another incision (different incision group: DI group, n = 23). We performed 2 jejunostomies, 13 ileostomies, and 1 colostomy in the SI group, and 4 jejunostomies, 18 ileostomies, and 1 colostomy in the DI group. One of 16 patients (6.3%) in the SI group and 2/23 patients (8.7%) in the DI group experienced superficial incisional SSI, with comparable SSI incidence between groups (p = 0.78). Every SSI did not result in stoma-related complications. Although the enterostomy location did not influence the incidence of laparotomy wound infection in this study, prospective studies are mandatory to fully assess the safety of enterostomy construction at the edge of the primary incision.

Purpose Gastroesophageal reflux after surgical repair of esophageal atresia (EA) can be associated with complications, such as esophageal stricture. Recent guidelines recommend prophylactic anti-reflux medication (PARM) after EA repair. However, the effectiveness of PARM is still unclear. The aim of this study was to review evidence surrounding the use of PARM in children operated for EA. Methods We performed a systematic review and meta-analysis. We searched Medline, EMBASE, and the Cochrane Databases from inception until the end of 2016 for comparative studies of PARM versus no PARM (control). Primary outcome was postoperative esophageal stricture. Quality of evidence was assessed using GRADE system. Results We identified four observational studies that focused on esophageal stricture as an outcome. A total of 362 patients were included in meta-analysis. There was no significant difference in esophageal stricture rates between PARM and control (OR = 1.14; 95% CI = 0.61–2.13; p = 0.68; I2 = 38%). The quality of the evidence was very low, due to lack of precision as a consequence of small study sizes. Conclusions Our results indicate that PARM does not reduce the incidence of esophageal stricture after EA repair. Future well-controlled prospective studies are needed to obtain higher quality evidence.

Administration of hyperosmolar formula is regarded as a risk factor for the development of necrotizing enterocolitis (NEC). However, there are limited number of reports about the relationship between formula osmolality and NEC. The aim of this study is to evaluate the effects of formula concentration in an experimental model of NEC. We studied experimental NEC in C57BL/6 mice. NEC was induced by giving hypoxia, gavage administration of lipopolysaccharide and gavage formula feeding from postnatal day 5–9. We used two types of formula: (1) hyperosmolar formula (HF): 15 g Similac + 75 ml Esbilac (849 mOsm/kg); (2) diluted formula (DF): dilute hyperosmolar formula with an equal amount of water (325 mOsm/kg). Controls were fed by the mother. On postnatal day 9, the ileum was harvested and evaluated for severity of mucosal injury (hematoxylin/eosin staining) and inflammation (PCR for IL6 and TNFα mRNA expression). The incidence of NEC was same in both HF and DF (80%). The intestinal inflammatory response was similar between HF and DF (IL6: p = 0.26, TNFα: p = 0.69). This study indicates the osmolality of enteral formula does not affect incidence of experimental NEC. This experimental study provides new insights into the relationship between formula feeding and NEC.

Maternal separation (MS) in neonates can lead to intestinal injury. MS in neonatal mice disrupts mucosal morphology, induces colonic inflammation and increases trans-cellular permeability. Several studies indicate that intestinal epithelial stem cells are capable of initiating gut repair in a variety of injury models but have not been reported in MS. The pathophysiology of MS-induced gut injury and subsequent repair remains unclear, but communication between the brain and gut contribute to MS-induced colonic injury. Corticotropin-releasing hormone (CRH) is one of the mediators involved in the brain–gut axis response to MS-induced damage. We investigated the roles of the CRH receptors, CRHR1 and CRHR2, in MS-induced intestinal injury and subsequent repair. To distinguish their specific roles in mucosal injury, we selectively blocked CRHR1 and CRHR2 with pharmacological antagonists. Our results show that in response to MS, CRHR1 mediates gut injury by promoting intestinal inflammation, increasing gut permeability, altering intestinal morphology, and modulating the intestinal microbiota. In contrast, CRHR2 activates intestinal stem cells and is important for gut repair. Thus, selectively blocking CRHR1 and promoting CRHR2 activity could prevent the development of intestinal injuries and enhance repair in the neonatal period when there is increased risk of intestinal injury such as necrotizing enterocolitis.

In sepsis, circulating free DNA (cf-DNA) is increased, and is a marker of severity and prognosis of septic patients. This study aimed to evaluate cf-DNA in a dextran sodium sulfate-induced colitis mouse model, and its clinical implications.Dynamic pathology of the cecum wall in the DSS-induced colitis mouse model was analyzed using multiphoton microscopy (MPM). Plasma cf-DNA concentrations in colitis mouse were quantified using PicoGreen dsDNA Assay Kit. Plasma cf-DNA was also measured in 123 human ulcerative colitis (UC) patients [mean age: 35.9 years (3-75 years) with 20 pediatric patients] to assess its relationships with clinical severity and Matt's grade.Real-time images of cf-DNA were detected in the colitis model. The amount of labeled cf-DNA in the circulation of the colitis mice group was significantly higher compared with that in the control group (P0.05). In human UC blood samples, plasma cf-DNA concentrations in UC patients were significantly positively correlated with the clinical severity of UC and Matt's grade (P0.05, P0.05, respectively).Using MPM, we observed and analyzed real-time images of cf-DNA in a colitis mouse model. Plasma cf-DNA is a potential non-invasive blood marker for reflecting clinical severity and mucosal damage in UC patients.

The aims of this study were to reveal how using the antibiotics recommended by the 2010 Surgical Infection Society (SIS) and Infectious Disease Society of America (IDSA) guidelines can affect the therapeutic outcomes. We reviewed the cases of 53 patients with a postoperative intra-abdominal abscess without anastomotic leakage after gastrointestinal surgery who underwent image-guided percutaneous abscess drainage (PAD) and concomitant antibiotic therapy. The type of antibiotic initially administered was determined based on the surgeon’s judgment. A persistent abscess was defined as one or more PAD procedures resulting in complete resolution after 21 or more days. The recommended antibiotics were defined according to 2010 SIS/IDSA guidelines. All 53 patients had complete resolution without the need for surgery. The results of a multivariable analysis revealed that a C-reactive protein level ≥12 mg/dL and non-recommended antibiotics were significant risk factors for a persistent abscess (P = 0.042 and 0.013, respectively). With regard to a fever lasting more than 48 h, there was a significant difference between the recommended (45.1 %) and non-recommended (72.7 %) antibiotic groups (P = 0.046). Using the recommended antibiotics may shorten the time to defervescence and reduce the risk of a persistent abscess in patients undergoing PAD for a postoperative abscess after gastrointestinal surgery.

N-myc downstream regulated gene 1 (NDRG1) markedly reduces metastasis of numerous tumors. However, NDRG1’s function in malignant tumors has not been fully determined. Therefore, we investigated the association of NDRG1 expression with clinical outcomes in neuroblastoma (NB) patients. We obtained total RNA from residual cancer cells using microdissection from NB patients. Furthermore, we examined the expression of NDRG1 in NB patients using immunohistochemical staining. Of the 48 patients observed, low NDRG1 expression was associated with poor prognostic factors such as primary tumor size and MYCN amplification. Low expression of NDRG1 was associated with a poor prognosis (p = 0.001) and multivariate analysis identified low expression of NDRG1 as an independent risk factor for predicting poor prognosis in NB patients. Furthermore, in the MYCN non-amplification group (n = 33), low expression of NDRG1 was associated with a poor prognosis (p = 0.001). Immunohistochemical analysis showed NDRG1 expression at the plasma membranes of NB cells. NDRG1 expression levels were also correlated with expression of NDRG1 mRNA. We confirmed that low NDRG1 expression is a significant and independent prognostic indicator in NB by multivariate analysis. Furthermore, NDRG1 may be a novel prognostic marker in MYCN non-amplification NB patients.

Although thrombus formation in vivo has recently been reported, all previous laser induced thrombus models have been associated with vessel wall disruption. This study aimed to evaluate in vivo real-time platelet aggregation after selective endothelial injury, and to visualize thrombus formation without disruption and swelling of the arterial intima induced by two-photon laser irradiation. Cecal arteriole thrombi were created in beta-actin-green fluorescent protein transgenic mice by selective endothelial injury using two-photon laser-scanning microscopy (TPLSM). The in vivo real-time process of thrombus formation was assessed. Anticoagulant drug efficiency for thrombi was also analyzed in detail. TPLSM allowed visualization of microvessel components from the arterial smooth muscle to the intimal layer. Immediately after selective laser irradiation of the intimal layer, platelet adhesion and aggregation were seen only at the area of injury of the intimal layer after forming linear adhesions downstream of the injured area. When shear stress was overcome, thrombus formation began at the downstream edge of the injured area. Thrombus volume plateaued approximately 60 min after laser irradiation. The thrombolytic effects of anticoagulant drugs were precisely assessed; therefore, our model appears the most advanced model in point of real-time imaging of pathophysiological processes in vivo currently reported. In vivo real-time imaging of thrombus formation can be achieved using TPLSM in combination with an organ stabilizing system. The high magnification and resolution of TPLSM allows investigation of the mechanisms of thrombus formation along with assessment of antithrombotic drug efficacy with little interexperimental variation.

The aim of this study was to determine if the placement of prophylactic drains influences the incidence of postoperative adverse events in neonates.Neonatal patients undergoing laparotomy between April 2000 and December 2007 were prospectively assigned to aggressive peritoneal cavity lavage, without the placement of prophylactic drains, before abdominal closure (non-drainage group, n = 111). The historical control group consisted of neonates who underwent laparotomy with routine prophylactic drain placement between January 1993 and March 2000 (drainage group, n = 87). The incidence of postoperative adverse events was compared between the two groups.There were no significant differences in the incidence of overall complications (drainage, 48%; non-drainage, 36%: p = 0.08), infectious complications (drainage, 34%; non-drainage, 26%: p = 0.20) or surgical site infections (drainage, 20%; non-drainage, 14%: p = 0.25) between the two groups. In the subgroup analysis, the incidences of total postoperative complications and infectious complications were significantly higher in the drainage group compared with the non-drainage group for upper gastrointestinal tract operations (52 vs. 20%; 39 vs. 6.7%) (p = 0.04 and 0.02, respectively).Prophylactic drainage did not reduce the incidence of postoperative complications, and the placement of drains may possibly increase the incidence of infectious complications.

We investigated the associations between hsMAD2 mRNA expression in tumor cells and sensitivity to paclitaxel or patient prognosis in neuroblastoma. Fifty-one formalin-fixed paraffin-embedded tumor samples were manually microdissected to collect tumor cells, and RNA was purified. Nineteen clinical samples of advanced neuroblastoma showed appropriate quality of the isolated RNA for real-time reverse transcription-polymerase chain reaction (RT-PCR) analyses. The hsMAD2 expression levels were determined by real-time RT-PCR in 4 neuroblastoma cell lines and 19 clinical samples. The sensitivity to paclitaxel was assessed by WST-8 colorimetric assays and flow cytometry. HsMAD2 expression of the clinical samples was investigated for its association with prognosis in advanced neuroblastoma patients. There was a significant positive correlation between hsMAD2 mRNA expression and the sensitivity to paclitaxel in four neuroblastoma cell lines. High hsMAD2 expression may be correlated with paclitaxel-induced apoptosis. Kaplan–Meier survival curves were stratified by hsMAD2 expression using the median value as a cut-off point and analyzed for prognostic significance by the log-rank test (P = 0.0467). Furthermore, multivariate survival analysis revealed that only hsMAD2 expression had a significant impact on the overall survival rate. Our results may warrant clinical application of paclitaxel in neuroblastoma treatment for poor prognosis patients.

The 13-year-old boy underwent tumor enucleation for pancreatic head insulinoma close to the pancreatic main duct after a preoperative endoscopic pancreatic stent placed by endoscopic retrograde cholangiopancreatography. The tumor was safely excised by identifying the indwelled pancreatic stent during the surgical procedure without pancreatic duct injury or postoperative complications.