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Background Patients with inflammatory bowel disease (IBD) are at a higher risk of developing cardiovascular diseases than healthy individuals, owing to persistent chronic inflammation and treatment effects. This study aimed to assess left ventricular function in patients with childhood-onset IBD using layer-specific strain analysis and to identify early indicators of cardiac dysfunction in them. Methods A total of 47 patients with childhood-onset ulcerative colitis (UC), 20 patients with Crohn’s disease (CD), and 75 age- and sex-matched healthy control subjects were included in this study. Conventional echocardiographic measurements of layer-specific (ie, endocardium, midmyocardium, and epicardium) global longitudinal strain and global circumferential strain (GCS) were evaluated in these participants. Results Layer-specific strain analysis showed that global longitudinal strain was lower in all layers for the UC (P < .001) and CD (P < .001) groups, regardless of the age at onset, but that GCS was only lower in the midmyocardial (P = .032) and epicardial (P = .018) layers in the CD group than in the control group. Although the mean left ventricular wall thickness was not significantly different among the groups, it was significantly correlated with the GCS of the endocardial layer in the CD group (ρ= -0.615; P = .004), suggesting that thickening of the left ventricular wall occurred as a compensatory mechanism to maintain the endocardial strain in the CD group layer. Conclusions Children and young adults with childhood-onset IBD displayed decreased midmyocardial deformation. Layer-specific strain could also be useful to identify indicators of cardiac dysfunction in patients with IBD.

Background and Aims Transabdominal ultrasonography [TAUS] appears comparable to colonoscopy for evaluating ulcerative colitis [UC] activity, but it has low accuracy in rectal evaluation. In this study, the accuracy of transperineal ultrasonography [TPUS] for evaluating rectal activity was compared to that of colonoscopy in paediatric UC cases. Methods Faecal calprotectin [FCP] values and TPUS and colonoscopic findings were compared prospectively in paediatric UC cases. Rectal wall thickening [RWT] and rectal wall flow [RWF] on power Doppler evaluated by TPUS were compared with the colonoscopy findings and were also measured on TAUS and assessed for the concordance rate of each finding. Results Thirty Mayo endoscopic sub-score [MES] 0–1 UC cases and 57 MES 2–3 UC cases were enrolled. FCP, RWT and RWF showed significant differences between the two groups [p Conclusions TPUS may evaluate rectal activity of UC with accuracy comparable to endoscopy. If accurate ultrasonic screening for the total colon can be performed by TPUS and TAUS, repeated evaluation of short-term treatment response may be possible.

Autoimmune enteropathy (AIE) is a rare disease, characterized by intractable diarrhea, villous atrophy of the small intestine, and the presence of circulating anti-enterocyte autoantibodies. Immune dysregulation, polyendocrinopathy, enteropathy, X-linked (IPEX) syndrome, and mutations in FOXP3, which is a master gene of regulatory T cells (Tregs), are major causes of AIE. Recent studies have demonstrated that mutations in other Treg-associated genes, such as CD25 and CTLA4, show an IPEX-like phenotype. We present the case of a 13-year-old girl with CTLA4 haploinsufficiency, suffering from recurrent immune thrombocytopenic purpura and intractable diarrhea. We detected an autoantibody to the AIE-related 75 kDa antigen (AIE-75), a hallmark of the IPEX syndrome, in her serum. She responded well to a medium dose of prednisolone and a controlled dose of 6-mercaptopurine (6-MP), even after the cessation of prednisolone administration. Serum levels of the soluble interleukin-2 receptor and immunoglobulin G (IgG) were useful in monitoring disease activity during 6-MP therapy. In conclusion, autoimmune-mediated mechanisms, similar to the IPEX syndrome, may be involved in the development of enteropathy in CTLA4 haploinsufficiency. Treatment with 6-MP and monitoring of disease activity using serum levels of soluble interleukin-2 receptor and IgG is suggested for such cases.

Introduction: Anal fistulae have a significant impact on the quality of life of patients with Crohn’s disease (CD). In this cross-sectional study, we aimed to determine whether biological agents were effective in treating anal fistulae in patients with CD. Methods: Fifty-three patients diagnosed with CD were retrospectively enrolled. Their data regarding symptoms, treatments, and disease progression from January 2007 to December 2016 were reviewed from the medical records. Fifteen (28%) patients with CD were complicated by anal fistulae. Results: The male-to-female ratio was 13:2, and the mean age at onset was 11 years and 6 months. Among the 15 patients, 14 (93%) had anal fistulae as an initial symptom. Almost all patients were treated by providing elemental diet, 5-aminosalicylic acid, and steroids as induction therapy. Biological agents were used in 8 patients (53.3%), and fistula closure was confirmed in all of them. Among the 7 patients not treated with biological agents, 1 (14.3%) had a recurrent anal fistula, while another had incomplete fistula closure. Regarding surgical management, 2 patients were treated using the seton method, and no patients required a colostomy. Conclusion: Treatment with biological agents is highly effective concerning the closure of anal fistulae in patients with CD, and reducing pain may improve their quality of life.

When an obstacle is moved in a superfluid faster than a critical velocity, quantized vortices are generated behind the obstacle. Here we propose a method to create more complicated topological excitations, three-dimensional skyrmions, behind a moving obstacle. We numerically show that, in a two-component Bose-Einstein condensate, component-dependent obstacle potentials can generate skyrmions in the wake, made up of quantized vortex rings in different components that are linked with each other. The lifetime of generated skyrmions can be prolonged by a guiding potential, which enables the formation of a skyrmion train., 7 pages, 5 figures, 8 movies

The diagnosis of Yersinia enterocolitica (Ye) enteritis is not easy because detection from stool culture is more difficult for Ye than for other bacterial enteritides. The establishment of characteristic ultrasonographic findings for Ye enteritis would help improve the detection rate of Ye enteritis along with performance of several cold cultures. This would facilitate appropriate selection of antibiotics based on antimicrobial susceptibility testing and contribute to a more accurate understanding of local public health. This study aimed to retrospectively compare ultrasonographic findings and clinical features between children with Ye enteritis and other bacterial enteritides.We identified patients treated for Ye enteritis (Ye group; n = 27) or other bacterial enteritides (Other enteritis group; n = 29) between 2014 and 2018. Ultrasonographic findings (including mean maximum diameter and mean major-minor axis ratio of ileocecal lymph nodes, wall thickness of the terminal ileum, and presence of a pericecal hyperechoic region), clinical symptoms, and laboratory findings at first visit were compared between groups.No difference in mean maximum diameter of ileocecal lymph nodes was seen between groups. However, mean major-minor axis ratio of ileocecal lymph nodes was lower in the Ye group than in the Other enteritis group (p 0.001). Presence of a pericecal hyperechoic region was more frequent in the Ye group than in the Other enteritis group (p 0.001). The combined presence of a mean ileocecal lymph node major-minor axis ratio1.51 and a pericecal hyperechoic region offered 100% sensitivity.Characteristic ultrasonographic findings identified in this study may improve ultrasonographic differentiation of Y. enterocolitica enteritis from other bacterial enteritides.

The incidence of perforation during antibiotic therapy (AT) of children triaged as non-complicated acute appendicitis (NC-Ap) was investigated. Abdominal ultrasonography (US) and/or computed tomography (CT) scans from cases of perforation identified at appendectomy for failed AT were reassessed blindly by a panel of board-certified specialists for any evidence of pre-AT morbidity suggestive of perforation. Of 521 cases triaged as NC-Ap, symptoms resolved with AT in 452 cases (86.8%). All 69/521 (13.2%) cases with persistent symptoms had urgent appendectomy, and 12/521 (2.3%) were found to have perforated. Blind reassessment of US and/or CT scans from these cases identified seven with evidence of perforation when they were triaged as NC-Ap. Thus, the actual incidence of perforation during AT for NC-Ap was actually 12–7 = 5/521 (0.95%). Perforation is generally believed to be a complication of AT, but inappropriate triaging of cases for AT can bias results by artificially inflating the number of perforations, in this study, by more than double. We are the first to assess the unbiased incidence of perforation during AT for NC-Ap, by reassessing pre-AT US and/or CT scans. The incidence of perforation during AT is actually negligible.

Background: The correlation between small intestinal motility alteration and irritable bowel syndrome (IBS) is not well evaluated. Aims: To assess the small intestinal and colonic transits in an IBS rat model with restraint stress and determine the role of small intestinal motility in the IBS pathophysiology.Methods: Restraint stress was utilized to make adolescent IBS rat models that were evaluated for clinical symptoms, including stool frequency and diarrhea. The small intestinal motility and transit rate were also evaluated. The amounts of mRNA encoding corticotropin-releasing hormone, mast cell, and serotonin (5-Hydroxytryptamine; 5-HT) receptor 3a were quantified using real-time polymerase chain reaction (PCR); the 5-HT expression was evaluated using immunostaining.Results: Restraint stress significantly increased the number of fecal pellet outputs, stool water content, and small intestinal motility in the IBS rat models. There was no difference in real-time PCR results, but immunostaining analysis revealed that 5-HT expression in the small intestine was significantly increased in the IBS rat models.Conclusions: In the adolescent rat model of IBS with restraint stress, we observed an increase in small intestinal and colonic motility. In the small intestine, enhanced 5-HT secretion in the distal portion may be involved in increasing the small intestinal motility.

In classical fluids, surfactants enter the interface between two immiscible fluids and reduce the interfacial tension. We show that a similar situation can be realized in a three-component Bose-Einstein condensate (BEC), in which a phase-separated two-component BEC forms an interface and the third component enters the interface. We derive an expression for the interfacial tension of this system, and numerically show that the third component can reduce the interfacial tension, i.e., the third component plays the role of a surfactant. The stability of such an interface is corroborated by the Bogoliubov analysis. We also consider a system that has a spatial gradient in the interfacial tension, and we show that interfacial flow is induced, which resembles the Marangoni flow in classical fluids.

Introduction: Long-term disease duration of ulcerative colitis (UC) is known to increase the risk of developing colorectal cancer in adults; however, this association has not been genetically analyzed in children with UC. Herein, we examined the expression of cancer-related genes in the colonic mucosa of pediatric UC patients and their risk of developing colorectal cancer. Methods: Microarray analysis of cancer-related gene expression was conducted on rectal mucosa biopsy specimens randomly selected from pediatric cases, including 4 active-phase UC cases, 3 remission-phase UC cases, and 3 irritable bowel syndrome control cases. The subject pool was then expanded to 10 active-phase cases, 10 remission-phase cases, and 10 controls, which were analyzed by real-time polymerase chain reaction (PCR) and immunohistochemical staining. Results: The microarray results indicated significantly higher expression levels of cancer-related genes PIM2 and SPI1 in the active group than in the remission and control groups (p < 0.05). Real-time PCR confirmed that PIM2 and SPI1 expression levels were significantly higher, whereas TP53 and APC expression levels were significantly lower, in the active-phase group than in the remission and control groups (p < 0.05). Immunohistochemical staining for PIM2, SPI1, TP53, and APC proteins supported the real-time PCR results. Conclusions: Expression levels of previously unreported cancer-related genes in adult UC patients were significantly higher in pediatric UC patients than in controls. Inflammation of the gastrointestinal mucosa increased the expression levels of cancer-related genes even in childhood-onset UC cases, suggesting that chronic inflammation from childhood may increase the risk of colorectal cancer development.

BACKGROUND Some monogenic inflammatory bowel diseases (IBDs) are known to be refractory to conventional treatments. Although allogeneic hematopoietic stem-cell transplantation (allo-HSCT) has become a curative therapeutic option for certain monogenic IBDs, its effectiveness regarding endoscopic improvements has not been clarified. METHODS The clinical course and endoscopic findings of patients with monogenic IBDs who were treated with allo-HSCT between December 2017 and November 2018 at the National Center for Child Health and Development, were retrospectively reviewed. The clinical disease activity was assessed using the weighted Pediatric Crohn's Disease Activity Index (wPCDAI) and the endoscopic finding was evaluated using the Simple Endoscopic Score for Crohn's Disease (SES-CD). Clinical remission was defined as a wPCDAI

Background Granulomatosis with polyangiitis (GPA) is a syndrome of refractory vasculitis in the upper respiratory tract, lungs, kidneys, and systemic small and medium-sized arteries; adults and children have similar courses. A pediatric GPA case with a preceding bloody pericardial effusion, which caused cardiac tamponade, and bloody stool has not been reported. Case presentation: A 14-year-old boy was referred for the evaluation of prolonged fever. He had chest pain and bloody stools, and diagnostic imaging showed a pericardial effusion. Immediately after admission, his systolic blood pressure decreased (85/70 mmHg), and pericardiocentesis was performed, with aspiration of approximately 500 mL of bloody pericardial fluid. Because pericardiocentesis increased the blood pressure (115/65 mmHg), the cause of the blood pressure decrease was diagnosed as cardiac tamponade. Because the pericardial fluid cytology was negative for malignant disease, as were chest MRI and gallium scintigraphy, colonoscopy was performed and showed multiple irregular-shaped aphthae from the right transverse colon to the cecum on the contralateral side of the mesenteric attachments, and a biopsy of the aphthous region showed necrotizing granulomatous inflammation. The patient also had an elevated serine proteinase 3-anti-neutrophil cytoplasmic antibody (PR3-ANCA) level (141 IU/mL) on serological examination. Head MRI showed thickening of nasal and sinus mucosa and a cystic mass in the left sphenoid sinus. Therefore, GPA was diagnosed based on these findings, and treatment with oral prednisolone (PSL) and azathioprine was started. After the treatment, the bloody stool disappeared, and there was no recurrence of pericardial effusion even after completing PSL tapering, and the PR3-ANCA level was maintained in the normal range. Conclusions Although pericarditis is a common cardiac complication of GPA, there have been no previous reports of cardiac tamponade due to pericarditis. This is the first case of a pediatric patient with cardiac and gastrointestinal complications preceding the main symptoms, including upper and lower respiratory tract and renal symptoms, although cases of GPA with bloody stools are extremely rare. In conclusion, the sequencing of measuring ANCA levels appears important assuming the vasculitic syndrome as one of differential diseases causing persistent fever and bloody stool including such as the inflammatory bowel disease.

BACKGROUND Helicobacter pylori (H. pylori) infection causes chronic gastritis, duodenal and to a lesser extent, gastric ulcers, and gastric cancer. Most H. pylori infections are acquired in childhood, and effective treatment of childhood infection is very important. Esophagogastroduodenoscopy (EGD) is useful for endoscopic diagnosis, mucosal tissue biopsy, and culture examination for H. pylori in children and adults. In this paper, we report results of susceptibility tests and eradication rates in H. pylori-positive children who underwent EGD over a 12-year period. MATERIALS AND METHODS The subjects were H. pylori-positive pediatric patients who had gastrointestinal symptoms and underwent EGD in the Department of Pediatrics, Juntendo University Hospital (January 2007-December 2018). Patients underwent serum IgG antibody tests, fecal antigen tests, or urea breath tests, and subsequently, culture tests by gastric mucosal biopsy during EGD. H. pylori positivity was defined as a positive result on both tests. Patients received triple therapy for 14 days using our regimen, and eradication was assessed at 2, 6, and 12 months after therapy. RESULTS Forty-five patients were H. pylori-positive, and the overall clarithromycin (CAM) resistance rate was 71.1 % (32/45). The CAM resistance rate for the 2013-2018 period was significantly higher than the 2007-2012 period (52.6% vs. 84.6%, P

Evidence relating to the efficacy of Helicobacter pylori eradication therapy for chronic immune thrombocytopenic purpura (cITP) in childhood is inadequate. The aim of this retrospective study was to determine the efficacy of H. pylori eradication therapy for platelet response in pediatric patients with cITP in our hospital, and to perform a systematic review of previous reports about pediatric patients with cITP who were positive for H. pylori infection and were treated with H. pylori eradication therapy. Analysis of the data of pediatric patients with cITP in our hospital and a systematic review of digital literature databases of studies in pediatric patients with cITP were performed. Data of 33 pediatric patients with cITP from our hospital records showed that the prevalence of H. pylori infection and the rate of response to platelet therapy were 15% and 33.3%, respectively. Data of 706 pediatric patients from 18 previous reports showed that the prevalence of H. pylori infection and rate of platelet response were 23% and 43.8%, respectively. Eradication therapy for H. pylori infection in pediatric cITP patients can be expected to result in a response equivalent to that in the adult population, with fewer adverse effects than other treatments for cITP.

Evidence relating to the efficacy of Helicobacter pylori eradication therapy for chronic immune thrombocytopenic purpura (cITP) in childhood is inadequate. The aim of this retrospective study was to determine the efficacy of H. pylori eradication therapy for platelet response in pediatric patients with cITP in our hospital, and to perform a systematic review of previous reports about pediatric patients with cITP who were positive for H. pylori infection and were treated with H. pylori eradication therapy. Analysis of the data of pediatric patients with cITP in our hospital and a systematic review of digital literature databases of studies in pediatric patients with cITP were performed. Data of 33 pediatric patients with cITP from our hospital records showed that the prevalence of H. pylori infection and the rate of response to platelet therapy were 15% and 33.3%, respectively. Data of 706 pediatric patients from 18 previous reports showed that the prevalence of H. pylori infection and rate of platelet response were 23% and 43.8%, respectively. Eradication therapy for H. pylori infection in pediatric cITP patients can be expected to result in a response equivalent to that in the adult population, with fewer adverse effects than other treatments for cITP.

Intravenous administration of the brand formulation of rocuronium bromide, currently used as a muscle relaxant, has been associated with vascular pain accompanied by withdrawal movements of the arm and wrist. The purpose of this study was to identify the cause of vascular pain induced by the brand formulation and to develop a new rocuronium formulation, not causing vascular pain, using a vascular pain-evoked flexor reflex response model of anesthetized rats. A rat flexor reflex model, monitored by electromyography, was used to evaluate a flexor reflex response as the index of vascular pain. A catheter for drug administration was inserted into the superficial caudal epigastric artery. A needle electrode was inserted into a muscle in the femoral area to obtain an electromyogram (EMG) value. The integrated EMG values obtained after the administration of each test drug were compared to the baseline value and quantified. The acetate buffer contained in the solvent could cause flexor reflex response. Furthermore, the flexor reflex response increased in an acid concentration-dependent manner. Based on these results, we prepared a new rocuronium formulation using a low-acid-concentration buffer solution and found that it decreased the integrated EMG value in the rat model. The integrated EMG value acquired using the brand formulation was reduced by pretreatment with the TRPA1 channel inhibitor. Our findings suggest that the high acid concentration in the brand formulation buffer solution is the cause of vascular pain. The rocuronium formulation developed using a low-acid-concentration buffer solution might help eliminate vascular pain in the clinic.

Background: Yersinia enterocolitica (Ye) causes enteritis with mesenteric lymphadenitis and terminal ileitis, and can be difficult to distinguish from acute appendicitis, especially in children. In addition, because detection from stool culture is more difficult for Ye than for other bacteria causing enteritis, the diagnosis of Ye enteritis is not easy. Abdominal ultrasonography is useful for diagnosing bacterial enteritis, including Ye enteritis. This study diagnosed Ye enteritis and other bacterial enteritis by stool culture and compared and analyzed the ultrasonic findings and clinical features in children. The aims of this study are to compare and analyze ultrasonic findings and clinical features in children with Ye enteritis and other bacterial enteritis.Methods: Participants in this retrospective study comprised all 34 bacterial enteritis patients (3-18 years old) treated between 2014 and 2017. Patients were divided into the Yersinia enterocolitica enteritis (Ye) group and other bacterial enteritis (non-Ye) group from whom other pathogens were detected. Ultrasonic findings (including maximum and minimum diameters of ileocecal lymph nodes (C-LNs), mean major/minor axis ratio, wall thickness of the terminal ileum, and presence of a pericecal hyperechoic region) and blood examinations at first visit were compared between two groups. Results: The Ye group included 13 patients and the non-Ye group included 21 patients. Mean C-reactive protein level was higher in the Ye group (5.9±3.0 mg/dL) than in the non-Ye group (2.7±3.4 mg/dL, p = 0.049). No difference in mean maximum diameter of C-LNs was seen between two groups. However, mean C-LN major/minor axis ratio was lower in the Ye group than in the non-Ye group (p = 0.002) and terminal ileal wall thickness value was higher in the Ye group than in the non-Ye group (p = 0.004). Pericecal hyperechoic region was more frequent in the Ye group than in the non-Ye group (p = 0.021). Conclusion: The combination of characteristic ultrasonic findings identified in this study may improve ultrasonic differentiation of Yersinia enterocolitica enteritis and other bacterial enteritis.

Proper diagnosis in the pediatric population is required to eradicate Helicobacter pylori (H. pylori) and prevent gastric cancer. Our aim was to assess the performance of non-invasive tests to diagnose H. pylori infection in pediatric patients. A retrospective analysis was performed on 141 pediatric patients requiring endoscopic evaluation and diagnostic tests for H. pylori infection to define the cause of abdominal symptoms. Non-invasive tests included the 13C-urea breath test (UBT), a monoclonal stool antigen test using enzyme-linked immuno-sorbent assay (mSAT), and a serum immunoglobulin G antibody test using antigens derived from Japanese individuals (S-Ab). This study investigated sensitivity, specificity, likelihood ratios for a positive and a negative test (LR+ and LR-), and accuracy of non-invasive tests, in comparison with invasive tests. Eighty two of 141 patients (58%) were recognized as H. pylori positive by invasive methods. When UBT, mSAT or S-Ab were analyzed, all were found to be effective over 94% accurate. Specificity ranged between 86.7% and 95.8%, and sensitivity ranged between 93.8% and 97.1%. When subjects were stratified into three distinct age groups, the best performance was achieved for 1-6 years old with mSAT at 100% for sensitivity, specificity, and accuracy. S-Ab yielded the best results for children 7-12 years old and the UBT test performed best for 13-18 years old. These results demonstrate the utility of UBT, mSAT, and S-Ab non-invasive tests in diagnosing H. pylori but suggest that certain tests may be optimal for children of distinct ages. Three non-invasive tests, UBT, mSAT and S-Ab showed sufficient sensitivity, specificity and accuracy for the initial diagnosis of H. pylori infection among pediatric patients. Non-invasive tests may contribute to achieving minimum invasive diagnosis with combining with a histological test and a culture test in children.

Helicobacter pylori (H. pylori) eradication rates achieved with a proton pump inhibitor (PPI), amoxicillin and clarithromycin have recently decreased to about 75% because of the increase in clarithromycin resistance in Japan. In the present study, H. pylori resistance rates against clarithromycin, amoxicillin and metronidazole were investigated in pediatric patients and eradication rates were evaluated when tailored antibiotics regimens based on antibiotic sensitivity data were used. We isolated H. pylori endoscopically from 77 pediatric patients suffering from abdominal symptoms. The susceptibility tests of H. pylori strains to clarithromycin, amoxicillin and metronidazole were examined and eradication therapy was tailored using the appropriate antibiotics. Seventy-seven patients were treated with a mean age of 12.16 ± 3.34 years (range, 4.92-19.75) consisting of 40 males and 37 females. The average resistance rates between 1998 and 2016 to clarithromycin, amoxicillin and metronidazole were 54.5% (42 of 77), 6.5% (5 of 77) and 5.2% (4 of 77) respectively. The prevalence of clarithromycin resistance increased significantly over time to reach 88.9% by 2013-2016. Successful eradication rates using tailored antibiotic treatment was 93.8% (61 of 65). Clarithromycin-based eradication therapy rate reached 92.6% against clarithromycin-sensitive strains. Metronidazole-based initial eradication therapy also had a high successful rate (97.0%) to clarithromycin-resistant strains. Although high rates of clarithromycin resistant H. pylori reaching about 90% were observed in Japanese children, tailored eradication therapy using the appropriate antibiotic agents were highly successful. H. pylori sensitivity testing and eradication therapy with appropriate antibacterial agents may contribute to accomplishment of high initial eradication rates and consequently reducing the incidence of developing gastric cancer.

Purpose The purpose of this study was to examine whether acute non-perforated appendicitis (ANPA) can be safely triaged by a pediatrician for conservative management (CM) using gray-scale ultrasonography with power Doppler (GSPD). Method Seventy five cases of ANPA assessed by a pediatrician with GSPD (2013–2015) were reviewed. GSPD grading for ANPA was: I: slightly irregular wall/normal blood flow; II: irregular wall/increased blood flow; III: irregular wall/decreased blood flow; and IV: absence of wall/blood flow. Grades I/II were managed conservatively with intravenous antibiotics then encouraged to book for interval appendectomy (IA). Grades III/IV were reviewed for emergency appendectomy (EA) by a pediatric surgeon. Results GSPD grading was I ( n =26), II ( n =36), III ( n =9), and IV ( n =4). EA was required for 5 cases, one grade III, and four grade IV cases. One grade IV case was treated conservatively after surgical review but EA was unavoidable. Of the remaining 70 cases discharged well after a mean of 5.7days hospitalization, 25/70 had IA with chronic inflammation on histology, 6/70 had recurrence of ANPA treated successfully by EA, and 39/70 remain asymptomatic at least 10months after declining IA. Overall, GSPD triaging with CM was cheaper than surgery. Conclusions GSPD performed by pediatricians appears to be safe/effective for triaging ANPA. Level of evidence Level III.

Background Although Helicobacter pylori infection among adults is a major risk factor for the development of gastric cancer and initial infection with H. pylori may occur before 5 years of age, the direct effects of H. pylori infection since childhood on gastric mucosa are unknown. The aim of this study was to evaluate gene expression in the H. pylori-infected gastric mucosa of children. Methods Gastric mucosal samples were obtained from 24 patients (12 adults and 12 children) who had undergone endoscopic evaluation of chronic abdominal complaints and were examined by the adult and pediatric gastroenterologists at Juntendo University Hospital. Six adult and pediatric patients with and six without H. pylori infection were enrolled. Their gastric mucosal samples obtained from the antrum and corpus were used for microarray, real-time polymerase chain reaction, and immunohistochemical analyses to examine the expression of inflammatory carcinogenic molecules. Results The expression of inflammatory molecules was upregulated in the H. pylori-infected gastric mucosa from both adults and children. The expression of olfactomedin-4 was only upregulated in adult patients, while that of pim-2, regenerating islet-derived 3 alpha, lipocalin-2, and C-X-C motif chemokine ligand 13 was equally upregulated in the infected gastric mucosa of both adults and children. Conclusions Because several carcinogenic molecules are upregulated in H. pylori-infected gastric mucosa even in children, early eradication therapy from childhood may be beneficial to decrease the incidence of gastric cancer. Although increased expression of olfactomedin-4 can be important in suppressing gastric cancer in adults, the increase was not detected in children.

Collagenous sprue (CS) is a severe malabsorption disorder, the etiology of which has not been well defined. Herein, we report the case of a 3-month-old infant with CS who responded to steroid and immunomodulator treatment and presented a thick subepithelial collagen band. A 3-month-old Japanese girl presented with severe watery diarrhea that lasted for 2 weeks. She was admitted to the referring hospital, but symptomatic improvement was not achieved with fasting and rehydration. Gastroduodenal endoscopy showed an edematous duodenal mucosal surface. Duodenal biopsy indicated severe villous atrophy with infiltration of mostly CD8-positive T cells; and deposition of subepithelial collagen was confirmed. The subepithelial collagen deposits, however, had disappeared after treatment. Historically, child-onset CS is extremely rare and this case is likely to be the youngest case of infantile CS. The present case suggests that CS should be considered as a differential diagnosis for intractable diarrhea, even in infants.

Background Despite the presence of ganglion cells in the rectum, some patients have symptoms similar to those of Hirschsprung's disease. A consensus has yet to be established regarding the terminology for these diseases. We defined this group of diseases as "allied disorders of Hirschsprung's disease" and compiled these guidelines to facilitate accurate clinician diagnosis and provide appropriate treatment strategies for each disease. Methods These guidelines were developed using the methodologies in the Medical Information Network Distribution System (MINDS). Of seven allied disorders, isolated hypoganglionosis; megacystis-microcolon-intestinal hypoperistalsis syndrome; and chronic idiopathic intestinal pseudo-obstruction were selected as targets of clinical questions (CQ). In a comprehensive search of the Japanese- and English-language articles in PubMed and Ichu-Shi Web, 836 pieces of evidence related to the CQ were extracted from 288 articles; these pieces of evidence were summarized in an evidence table. Results We herein outline the newly established Japanese clinical practice guidelines for allied disorders of Hirschsprung's disease. Given that the target diseases are rare and intractable, most evidence was drawn from case reports and case series. In the CQ, the diagnosis, medication, nutritional support, surgical therapy, and prognosis for each disease are given. We emphasize the importance of full-thickness intestinal biopsy specimens for the histopathological evaluation of enteric ganglia. Considering the practicality of the guidelines, the recommendations for each CQ were created with protracted discussions among specialists. Conclusions Clinical practice recommendations for allied disorders of Hirschprung's disease are given for each CQ, along with an assessment of the current evidence. We hope that the information will be helpful in daily practice and future studies.

Background Although pediatric inflammatory bowel disease (IBD) is characterized by extensive intestinal involvement and rapid early progression, the precise cause and specific factors involved in disease aggravation have not been well established. The aim of this study was to investigate the pathogenesis of pediatric IBD. Methods The expression of inflammatory molecules in colon samples taken from active ulcerative colitis (UC) and Crohn's disease (CD) patients was compared with those of controls. Three children each with UC and CD in both the active and remission phase and their controls were enrolled, and the inflammatory gene expression in the mucosa was examined by microarray. Additionally, six children from each group were further enrolled in a real-time reverse transcription polymerase chain reaction and an immunohistochemical study to examine the expression of CXCL9, 10, 11, CXCR3, matrix metalloproteinase (MMP)-1, -3, -7, and -10. Results The microarray analysis revealed enhanced expression of the CXCL9, 10, and 11 genes in the active phase of CD. The expression of MMP-1, -3, -7, and -10 was significantly enhanced in the active phase of UC. These changes were also confirmed by real-time reverse transcription polymerase chain reaction. Immunohistochemical analysis revealed enhanced expression of CXCL9, 10, and 11 in both the lamina propria and epithelial cells in these patients. CXCR3-positive cells were also confirmed in the lamina propria. The expression of MMP-1, -3, -7, and -10 was also enhanced in the mucosal epithelial cells and the lamina propria in both CD and UC patients. Conclusions These findings suggest that CXCR3 axis components and MMP play an important role in the mucosal damage in pediatric IBD.

Background Although rectal bleeding in infancy (RBI) is not a rare phenomenon, the clinical course of RBI is not fully understood. Methods To investigate the outcome and pathogenesis of RBI, especially when concomitant with food-protein-induced proctocolitis (FPIP) and neonatal transient eosinophilic colitis (NTEC), 22 neonates with rectal bleeding with FPIP and NTEC from January 2008 to June 2012 were enrolled and their clinical course and mechanisms of inflammation were examined. Results Thirteen infants showed rectal bleeding after feeding and were diagnosed with FPIP, and nine infants showed rectal bleeding before feeding and were diagnosed with NTEC. Elevated peripheral white blood cell (12 685 ± 3754/μl and 30 978 ± 16 166/μl) and eosinophil (1084 ± 816/μl and 4456 ± 3341/μl) were confirmed in FPIP and NTEC, respectively. Colonoscopy revealed nodular lymphoid hyperplasia, a pale mucosal surface and oozing with diffuse infiltration of neutrophils, lymphocytes, and eosinophils in both groups. Reverse transcription polymerase chain reaction analysis revealed enhanced expression of the interleukin-6, CCL11, and CXCL13 genes, where CXCL13 expression was more prominent in FPIP. Mucosal infiltration by CD3- and immunoglobulin-A- but not immunoglobulin-E-positive cells was confirmed. Among them, only one infant with FPIP developed milk allergy, whereas none with NTEC had developed milk allergy at the age of 1 year. Conclusions FPIP in infancy and NTEC are similar diseases and interleukin-6, CCL11, and CXCL13 may play a major role in the pathogenesis of rectal bleeding. Although the involvement of allergic reaction is possible, milk allergy was not a common outcome after 1 year of follow up.

The prevalence of ulcerative colitis (UC) differs by country, which is likely due to differences in genetic factors among ethnicities. Moreover, the prevalence of pediatric UC with a family history (FH) is 4.1% in Japanese patients; its clinical course begins at an early age and is more severe. Recently, a genome-wide association study identified 3 new susceptibility loci for adult Japanese patients with UC.To assess the effects of FH in patients with UC, 60 children were enrolled. Age at diagnosis, clinical features of the initial symptoms, and family structure were assessed in patients with and without an FH. The 3 new loci were examined in patients who provided informed consent.Of the patients with UC, 10 (16.7%) had an FH involving first-degree relatives, including 7 mothers, 1 father, and 2 sisters. There was a trend toward a younger age at onset in the positive FH group. There were, however, no significant differences in the clinical characteristics of the patients regardless of FH. From the genomic analyses, there were significant differences in the polymorphisms of the solute carrier family 26, member 3 (SLC26A3) between those with and without an FH.Although the etiology of UC remains unknown, there were no observed relation between clinical symptoms and FH. SLC26A3 may, however, contribute to the pathogenesis of UC in Japanese individuals with an FH.

Background: Although initial infection with Helicobacter pylori may occur before 5 years of age, the pediatric mucosal immune response against H. pylori is not clear. The aim of the present study was to evaluate immune responses in the H. pylori-infected gastric mucosa of children using microarray and real-time polymerase chain reaction (PCR) analysis of pediatric gastric samples. Methods: Gastric samples were obtained from 12 patients undergoing routine endoscopy of chronic abdominal complaints. Six patients (three boys, three girls) aged 10.1–14.6 years had evidence of H. pylori infection, and the remaining six (three boys, three girls) aged 10.3–15.5 years had no evidence of infection and presented no histological changes associated with gastritis. Microarray and real-time PCR analyses were performed, and the changes in gene expression-related immune response were also analyzed. Results: Using microarray analysis, the total number of significantly upregulated and downregulated genes (fold change >5, P