Characteristics and Frequency of Pediatric Inflammatory Bowel Disease-Associated Pancreatitis: A Japanese Nationwide Survey.

Acute pancreatitis (AP) develops in approximately 2% of patients with the diagnosis of inflammatory bowel disease (IBD), but the characteristics and frequency of childhood-onset IBD-associated AP in Japan have not been studied. The present study aimed to clarify the characteristics of IBD-associated AP in Japan. Methods: A nationwide survey of pediatric patients with IBD (age, <17 years) was conducted from December 2012 to March 2013 at 683 hospitals and medical centers in Japan. A secondary survey was also sent to the centers with the target patients to evaluate their characteristics. Results: The response rate to the first part of the survey was 61.2% (n = 418). In total, 871 patients with Crohn disease and 1671 patients with ulcerative colitis were enrolled. The second part of the survey found that 11 (1.3%) patients with Crohn disease and 23 (1.4%) patients with ulcerative colitis experienced IBD-associated AP caused by medication (n = 18, 53%), a primary disease (n = 11, 32%), autoimmune pancreatitis (n = 1, 3%), or an anatomical abnormality (n = 1, 3%). All the patients had only mild AP. Conclusions: IBD-associated AP was not very frequent and was generally mild. The major cause of the pancreatitis was the medication used to treat the IBD.

The updated JSPGHAN guidelines for the management of Helicobacter pylori infection in childhood.

The Japan Pediatric Helicobacter pylori Study Group published the first guidelines on childhood H. pylori infection in 1997. They were later revised by the Japanese Society for Pediatric Gastroenterology, Hepatology and Nutrition (JSPGHAN). The H. pylori eradication rates, when employing triple therapy with amoxicillin and clarithromycin, currently recommended as the first-line therapy of H. pylori infection in Japan, have substantially decreased, creating an important clinical problem worldwide. In Japanese adults, the "test-and-treat" strategy for H. pylori infection is under consideration as an approach for gastric cancer prevention. However, the combined North American and European pediatric guidelines have rejected such a strategy for asymptomatic children. As risk for gastric cancer development is high in Japan, determining whether the "test-and-treat" strategy can be recommended in children has become an urgent matter. Accordingly, the JSPGHAN has produced a second revision of the H. pylori guidelines, which includes discussion about the issues mentioned above. They consist of 19 clinical questions and 34 statements. An H. pylori culture from gastric biopsies is recommended, not only as a diagnostic test for active infection but for antimicrobial susceptibility testing to optimize eradication therapy. Based upon antimicrobial susceptibility testing of H. pylori strains (especially involving clarithromycin), an eradication regimen including use of the antibiotics to which H. pylori is susceptible is recommended as the first-line therapy against H. pylori-associated diseases. The guidelines recommend against a "test-and-treat" strategy for H. pylori infection for asymptomatic children to protect against the development of gastric cancer because there has been no evidence supporting this strategy.

Tacrolimus for ulcerative colitis in children: a multicenter survey in Japan.

BACKGROUND/AIMS: Tacrolimus is effective for refractory ulcerative colitis in adults, while data for children is sparse. We aimed to evaluate the effectiveness and safety of tacrolimus for induction and maintenance therapy in Japanese children with ulcerative colitis. METHODS: We retrospectively reviewed the multicenter survey data of 67 patients with ulcerative colitis aged < 17 years treated with tacrolimus between 2000 and 2012. Patients' characteristics, disease activity, Pediatric Ulcerative Colitis Activity Index (PUCAI) score, initial oral tacrolimus dose, short-term (2-week) and long-term (1-year) outcomes, steroid-sparing effects, and adverse events were evaluated. Clinical remission was defined as a PUCAI score < 10; treatment response was defined as a PUCAI score reduction of ≥ 20 points compared with baseline. RESULTS: Patients included 35 boys and 32 girls (median [interquartile range] at admission: 13 [11-15] years). Thirty-nine patients were steroid-dependent and 26 were steroidrefractory; 20 had severe colitis and 43 had moderate colitis. The initial tacrolimus dose was 0.09 mg/kg/day (range, 0.05-0.12 mg/kg/day). The short-term clinical remission rate was 47.8%, and the clinical response rate was 37.3%. The mean prednisolone dose was reduced from 19.2 mg/day at tacrolimus initiation to 5.7 mg/day at week 8 (P< 0.001). The adverse event rate was 53.7%; 6 patients required discontinuation of tacrolimus therapy. CONCLUSIONS: Tacrolimus was a safe and effective second-line induction therapy for steroid-dependent and steroid-refractory ulcerative colitis in Japanese children.

Successful azathioprine treatment in an adolescent with chronic enteropathy associated with SLCO2A1 gene: A case report.

INTRODUCTION: Chronic nonspecific multiple ulcers of the small intestine (CNSU), an entity with female preponderance and manifestations including anemia and hypoproteinemia reflecting persistent gastrointestinal bleeding and intestinal protein loss, has been considered idiopathic. Umeno et al recently reported that CNSU is caused by loss-of-function mutations in the solute carrier organic anion transporter family member 2A1 gene (SLCO2A1) encoding a prostaglandin transporter, renaming the disorder "chronic enteropathy associated with SLCO2A1 gene mutation" (CEAS). Treatments for chronic enteropathies such as inflammatory bowel disease, including 5-aminosalicylic acid, corticosteroids, azathioprine, and anti-tumor necrosis factor-α antibody, often are ineffective in CEAS, which frequently requires surgery. CASE PRESENTATION: A 14-year-old girl had refractory anemia and hypoproteinemia for more than 2 years. Video capsule endoscopy showed nonspecific jejunal and ileal ulcers with varied sizes and shapes. She was diagnosed with CEAS resulting from compound heterozygous mutation of the SLCO2A1 gene. After corticosteroid treatment without improvement, azathioprine treatment improved her anemia and edema as hemoglobin and serum protein increased. Video capsule endoscopy 1 year after initiation of azathioprine showed improvement of small intestinal ulcers. CONCLUSION: Physicians should consider CEAS in patients with refractory anemia, hypoproteinemia, and multiple small intestinal ulcers. Why our patient responded to azathioprine but not to corticosteroids is unclear, but azathioprine might benefit some other patients with CEAS.

Japanese clinical practice guidelines for allied disorders of Hirschsprung's disease, 2017.

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.

Shwachman-Diamond syndrome: Nationwide survey and systematic review in Japan.

BACKGROUND: Shwachman-Diamond syndrome (SDS) is a rare multisystem disorder associated with exocrine pancreatic insufficiency. The present study reports the results of a nationwide survey and a systematic review on SDS to develop consensus guidelines for intractable diarrhea including SDS. METHODS: Questionnaires were sent to 616 departments of pediatrics or of pediatric surgery in Japan in a nationwide survey. A second questionnaire was sent to doctors who had treated SDS patients and included questions on clinical information. Additionally, a systematic review was performed using digital literature databases to assess the influence of medical (i.e. non-surgical) treatment on SDS prognosis. RESULTS: Answers were received from 529 institutions (85.9%), which included information on 24 patients with SDS (median age, 10.4 years; male, n = 15) treated from January 2005 to December 2014. Although 75% of patients received pancreatic enzyme replacement therapy, there was no significant association between treatment and prognosis. Systematic review identified one clinical practice guideline, two case series, eight case reports and 26 reviews. Patient information from those studies was insufficient for meta-analysis. CONCLUSIONS: The rarity of SDS makes it difficult to establish evidence-based treatment for SDS. According to the limited information from patients and published reports, medical treatment for malabsorption due to SDS should be performed to improve fat absorption and stool condition, but it is not clear whether this treatment improves the prognosis of malabsorption.

Epidemiologic features of 348 children with hepatitis C virus infection over a 30-year period: a nationwide survey in Japan.

BACKGROUND: Although the epidemiology of hepatitis C virus (HCV) infection among children may be rapidly changing, few reports have characterized large nationwide cohorts of children with HCV infection. We, therefore, sought to clarify the epidemiology and natural history of HCV infection in Japanese children born over the last three decades. METHODS: Sixty-five pediatric centers retrospectively and prospectively recruited consecutive, otherwise-healthy HCV-infected children born during 1986 to 2015. RESULTS: Entry criteria were met by 348 children. Age at initial diagnosis of infection has decreased significantly in recent years. Cirrhosis and hepatocellular carcinoma were not identified. Prevalence of spontaneous clearance and of interferon treatment with/without ribavirin were 9 and 54%, respectively. Maternal transmission has increased significantly, representing over 99% of cases in the last decade. No transfusion-related cases have been seen after 1994. HCV genotype 2 has increased to become the most prevalent in Japanese children. Histopathology examination of liver specimens showed no or mild fibrosis in most children with chronic hepatitis C; none showed cirrhosis. CONCLUSIONS: This largest nationwide cohort study of Asian children with HCV infection spanned the last three decades. None of these Japanese children developed cirrhosis or hepatocellular carcinoma. Maternal transmission increased to account for 99% of cases during the last decade. Genotype 2 now is most prevalent in these children. Histopathologically, most children with chronic hepatitis C showed mild fibrosis or none.

Study to determine guidelines for pediatric colonoscopy.

AIM: To investigated characteristics, diagnosis, bowel-cleansing preparation, sedation, and colonoscope length and diameter in Japanese pediatric patients receiving total colonoscopy. METHODS: The present study evaluated consecutive patients aged ≤ 15 years who had undergone their first colonoscopy in Kurume University between January 2007 and February 2015. Data were retrospectively analyzed. We identified 110 pediatric patients who had undergone colonoscopy that had reached the cecum, allowing the observation of the total colon. RESULTS: Hematochezia, abdominal pain, and diarrhea were the most common symptoms. For bowel-cleansing preparation, pediatric patients aged ≤ 12 years were treated with magnesium citrate, and patients aged 13-15 years were treated with polyethylene glycol 4000. For sedation, thiamylal with pentazocine, which has an analgesic effect, was used in patients aged ≤ 6 years, and midazolam with pentazocine was used in patients aged ≥ 7 years. Regarding the choice of endoscope, short and thin endoscopes were selected for younger patients, particularly patients aged ≤ 3 years. Positive diagnoses were made in 78 patients (70.9%). Inflammatory bowel disease (n = 49, 44.5%), including ulcerative colitis (n = 37, 33.6%) and Crohn's disease (n = 12, 10.9%), was the most common diagnosis. CONCLUSION: Colonoscopy offers a high diagnostic capability for pediatric patients with gastrointestinal symptoms. The selection of appropriate management the performance of colonoscopy is important in pediatric patients.

Immunosuppressive medication is not associated with surgical site infection after surgery for intractable ulcerative colitis in children.

Pediatric ulcerative colitis (UC) sometimes progresses to an intractable condition for medical therapy. The surgical management of UC is challenging because of difficult procedures and frequent infectious complications. The aim of this study was to survey surgical procedures and infectious complications in pediatric patients with UC in Japan and to assess the relationship between preoperatively administered immunosuppressive drugs and postoperative surgical site infection (SSI). A survey of pediatric patients treated from 2000 to 2012 was sent to 683 facilities nationwide. Secondary questionnaires were sent to physicians who followed up patients with UC who had undergone surgery with the aim of assessing the relationships between postoperative SSI and selected preoperative patient characteristics, disease severity, medications, and operative procedures. Data for 136 patients (77 boys and 59 girls) were assessed. Median age at surgery was 14.1 years (range: 2.4-18.9 years). Surgery was performed in one stage in 35 cases, two stages in 57 cases, and three stages in 44 cases. SSI occurred in 36/136 patients (26%). According to multiple logistic regression analysis, there were statistically significant associations between SSI and staged surgery (three/one, OR: 6.7, 95% CI: 2.1-25.5, p = 0.0007; three/two, OR: 3.4, 95% CI: 1.4-8.6, p = 0.0069) and female sex (OR: 2.3, 95% CI: 1.0-5.4, p = 0.0434). Preoperative medications and incidence of SSI were not significantly associated. Preoperative immunosuppressive medication does not affect the incidence of SSI. Three-stage surgery and female sex are independent predictors of development of postoperative SSIs in pediatric patients with UC.

Internal anal sphincter achalasia: data from a nationwide survey of allied disorders of Hirschsprung's disease in Japan.

PURPOSE: To investigate the incidence and treatment of internal anal sphincter achalasia (IASA) in Japan based on an analysis of data from a nationwide retrospective cohort study of the allied disorders of Hirschsprung's disease. METHODS: Five cases of definitive IASA were collected from a nationwide retrospective cohort study conducted from 2001 to 2010 and a search of the Japanese literature. RESULTS: Symptoms developed during the neonatal period in two patients, during early childhood in two, and at school age in one. Symptoms included abdominal distension with severe constipation (n = 4) and enterocolitis (n = 1). Rectocolonography showed megarectum and no narrow segment in most of the patients. All patients were negative for rectosphincteric reflex. The presence of ganglion cells was demonstrated by H&E or AChE staining from rectal mucosal biopsies or resected full-thickness segments. Two patients were treated conservatively, and three were treated surgically by internal anal sphincter myotomy (n = 2) or Lynn procedure (n = 1), with satisfactory outcomes. CONCLUSION: IASA is a rare but distinct entity in Japan. Although the clinical features of IASA resemble those of short- and ultrashort-segment HD, characteristic pathological findings include the presence of ganglion cells. The outcomes of both conservative and surgical treatment are good.

Natural history of chronic hepatitis B virus infection in children in Japan: a comparison of mother-to-child transmission with horizontal transmission.

BACKGROUND: It is necessary to evaluate the natural history of children with hepatitis B virus (HBV) infection in each country to consider their long-term management. METHODS: A multi-center observational study of children with chronic HBV infection who were diagnosed at age ≤15 years was carried out in 18 hospitals in Japan. RESULTS: We reviewed children with HBV infection including 381 with mother-to-child transmission (MTCT) and 154 with horizontal transmission, genotype C being the most prevalent virus genotype (83%). Children with horizontal transmission were more frequently infected with HBV genotype A or B and more likely to receive interferon therapy than those infected by MTCT. The HBeAg seroconversion rate at 15 years of age was 42% in the MTCT group and 38% in the horizontal group. It was lower in children with genotype C infection than in those infected with other genotypes (33 versus 45%). Hepatitis developed at any age but before 4 years of age the incidence was high in the horizontal group. At 3 years after the onset of the hepatitis, 26% of children with MTCT and 30% of those with horizontal transmission became inactive carriers. The incidences of hepatocellular carcinoma (HCC) at 30 years of age were 6% in the MTCT group and 11% in the horizontal group. CONCLUSIONS: Patients with childhood-onset HBV infection with MTCT and horizontal transmission developed hepatitis and seroconverted to anti-HBe at any age and had a lifetime risk of developing HCC.

Pharmacotherapy for pediatric chronic intestinal pseudo-obstruction: Nationwide survey in Japan.

BACKGROUND: Chronic intestinal pseudo-obstruction (CIPO) is a rare disabling and life-threatening disorder characterized by severe impairment of gastrointestinal peristalsis. While a number of pharmacotherapeutics have been developed, only a few trials have been carried out for improvement of the pathological condition of CIPO patients. This report describes the results of a nationwide survey on the pharmacotherapy used in pediatric CIPO in Japan. METHODS: In 2012, a nationwide survey was conducted to identify the clinical presentation of CIPO in Japan. Information was gathered on pharmacotherapy. Four categories were created for medicines used in pharmacotherapy: "probiotics", "Japanese herbal medicines (Kampo medicines)", "laxatives", and "prokinetics". RESULTS: Ninety-two responses were collected from 47 facilities. Of the 62 patients who met the diagnostic criteria, 52 were treated with medications, while the remaining 10 were not. Thirty-four patients were given a total of 49 probiotics; 39 were treated with a total of 50 Kampo medicines; 20 were treated with a total of 28 laxatives; and 26 were given a total of 30 prokinetics, 70% of whom were treated specifically with mosapride. CONCLUSION: Traditional Japanese medicines such as Kampo medicines and mosapride are often used to treat CIPO in Japan. Two combinations, that is, probiotics and Kampo medicines; and Kampo medicines and prokinetics, were often used for pediatric CIPO in Japan.

Treatment with infliximab for pediatric Crohn's disease: Nationwide survey of Japan.

BACKGROUND AND AIM: Childhood-onset inflammatory bowel disease (IBD) is characterized by extensive intestinal involvement and rapid early progression. Infliximab (IFX), cyclosporin (CYA), and tacrolimus (FK506) are increasingly used to treat pediatric IBD; however, their long-term effects and adverse events have not been properly investigated in pediatric patients. The aim of this study was to characterize the effects of these biologics and immunomodulators on pediatric IBD patients in Japan. Additionally, we assessed IFX use in pediatric patients with Crohn's disease (CD). METHODS: A national survey of IFX, adalimumab, CYA, and FK506 use in pediatric IBD patients (< 17 years of age) was sent to 683 facilities in Japan from December 2012 to March 2013. Secondary questionnaires were sent to pediatric and adult practitioners with the aim of assessing the effectiveness and safety of IFX for pediatric CD patients. RESULTS: The response rate for the primary survey was 61.2% (N  =  418). Among 871 pediatric CD patients, 284 (31.5%), 24, 4, and 15 received IFX (31.5%), adalimumab, CYA, and FK506, respectively, from 2000 to 2012. According to the secondary survey, extensive colitis (L3, Paris classification) was diagnosed in 69.4% of pediatric CD patients who received IFX. Regarding the effectiveness of IFX in this population, 54.7% (99/181) of patients were in remission, and 42.0% (76/181) were on maintenance therapy. However, 32.0% (58/181) of patients experienced adverse events, and one patient died of septic shock. CONCLUSIONS: Infliximab is reasonably safe and effective in pediatric CD patients and should therefore be administered in refractory cases.

Pediatric-onset Chronic Nonspecific Multiple Ulcers of Small Intestine: A Nationwide Survey and Genetic Study in Japan.

We performed a Japanese nationwide survey of pediatric-onset chronic nonspecific multiple ulcers of the small intestine between January 2000 and July 2013 in 176 institutions of pediatric surgery or pediatric gastroenterology and clarified the clinical features associated with genetic abnormalities in the Solute Carrier Organic Anion Transporter Family, Member 2A1 (SLCO2A1) gene. A total of 4 cases (3 girls and 1 boy) were diagnosed in this series, which had to be differentiated from Crohn disease, Behçet disease, tuberculosis, or drug-induced enteropathy. Clinical symptoms appeared in infants and accurate diagnosis required several years. Medical therapies for inflammatory bowel disease were administered in all patients; however, 2 of the 4 patients had mutation in the SLCO2A1 gene which are responsible for primary hypertrophic osteoarthopathy, and underwent strictureplasty or ileal resection after long-term follow-up. Pediatric gastroenterologists should include this new entity in the differential diagnosis of small intestinal ulcers and inflammatory bowel disease.

Hepatocellular carcinoma in children and young patients with chronic HBV infection and the usefulness of alpha-fetoprotein assessment.

The aims of the study were to elucidate the clinical characteristics of patients who developed hepatocellular carcinoma (HCC) related to persistent HBV infection since childhood and to investigate usefulness of assessing alpha-fetoprotein (AFP) in this population. A nationwide multicenter survey of children with chronic HBV infection was performed. Among 548 patients, 15 patients developed HCC at the median age of 15 years (range 9-36), including 13 males and 2 females. A case-control comparison showed that HBeAg seroconversion and liver cirrhosis were associated with the occurrence of HCC. Of the 15 HCC patients, 5 were treated with interferon and none of them responded to interferon therapy as compared with 12 of the 17 responders in the control group. Of the 15 patients, 10 died and 9 of the 10 who died never visited any medical facilities until diagnosis of HCC, while the remaining 5 surviving patients never stopped their clinic visits. The usefulness of AFP assessment was shown by the findings that AFP levels were elevated in all HCC cases, that elevations in AFP levels were detected prior to the diagnosis in the surviving patients, and that sensitivity of AFP as a diagnostic test for HCC was very high among 40 patients including our 14 and an additional 26 collected from the literature. HBeAg seroconversion and liver cirrhosis are associated with the occurrence of HCC. Regular measurement of AFP might be helpful to watch for the occurrence of HCC when following children and young patients with chronic HBV infection since childhood.

A role for fosfomycin treatment in children for prevention of haemolytic-uraemic syndrome accompanying Shiga toxin-producing Escherichia coli infection.

The role of antimicrobial therapy for Shiga toxin-producing Escherichia coli (STEC) infection has not been clearly defined. A prospective study identified antibiotic use as a significant risk factor for subsequent development of haemolytic-uraemic syndrome (HUS). However, early treatment with fosfomycin, a bacteriostatic antibiotic, resulted in a significantly decreased risk of HUS. The aim of this study was to evaluate a role of fosfomycin therapy in the development of HUS in children who contracted STEC infection. The study included 118 children who contracted a STEC infection between 1997 and 2013. A pre-defined questionnaire was utilised to collect patient information regarding age, sex, presenting symptoms (fever, abdominal pain, diarrhoea and bloody stool), results of stool culture examination, initial results of white blood cell counts and C-reactive protein (CRP), use of antibiotics, the timing of introduction of antibiotics, and complications including HUS. Of the 118 patients, 64 were diagnosed with HUS and the remaining 54 did not develop HUS. Multivariate analysis showed that three independent factors (age, initial values of CRP and use of fosfomycin) were significantly associated with the occurrence of HUS; of particular note, the adjusted odds ratio for use of fosfomycin was 0.15 (95% confidence interval 0.05-0.45). Use of fosfomycin within the first 5 days of illness may decrease the development of STEC-related HUS in children.

Serologic response after vaccination against influenza (A/H1N1)pdm09 in children with renal disease receiving oral immunosuppressive drugs.

A limited number of reports are available regarding the effect of the influenza vaccine in pediatric patients receiving steroid and immunosuppressant therapy. The influenza A(H1N1)pdm09 vaccine was administered to 15 children with renal disease who were receiving steroid and immunosuppressant therapy (treatment group) and 23 children with who were not receiving these drugs (non-treatment group). Titer transition of the hemagglutination inhibition antibody was compared between the 2 groups immediately before vaccination and 4 weeks and 6 months after vaccination. Multivariate analysis showed a significant correlation between geometric mean titer, SCR, and SPR with age, while no correlation was observed between treatment with immunosuppressant therapy and efficacy. No serious adverse reactions occurred after vaccination. This strain is not present in existing influenza vaccines, and A(H1N1)pdm09HA vaccination was administered alone in 2009. The children in this study had not previously been exposed to this strain. Therefore, we evaluated the effect of the A(H1N1)pdm09HA vaccine without the effects of vaccination or past infection with A(H1N1)pdm09HA or A(H3N2) vaccination in the previous year.

Pediatric chronic intestinal pseudo-obstruction is a rare, serious, and intractable disease: a report of a nationwide survey in Japan.

BACKGROUND/PURPOSE: A nationwide survey was conducted to identify the clinical presentation of pediatric chronic intestinal pseudo-obstruction (CIPO) in Japan. METHODS: Data were collected via a questionnaire, ensuring patient anonymity, from facilities that treat pediatric gastrointestinal diseases in Japan. RESULTS: Ninety-two responses were collected from forty-seven facilities. Sixty-two patients (28 males, 34 females) met formal diagnostic criteria for CIPO. The estimated pediatric prevalence was 3.7 in 1 million individuals. More than half the children (56.5%) developed CIPO in the neonatal period. Full-thickness intestinal specimens were available for histopathology assessment in forty-five patients (72.6%). Forty-one (91.1%) had no pathological abnormalities and were considered to be idiopathic. Patients were treated according to the local protocol of each facility. Forty-one patients (66.1%) had restricted oral intake of ordinary diets, and twenty-nine (46.8%) depended on parenteral nutrition. No therapeutic intervention, including medication and surgery, successfully improved oral food intake or obstructive symptoms. Only three patients (4.8%) died from enteritis or sepsis. CONCLUSIONS: In Japan, pediatric CIPO is a rare, serious, and intractable disease. The prognosis with respect to survival is good, but unsatisfactory because of the need for prolonged parenteral nutrition and associated potential for restricted quality of life.

The burden of rotavirus gastroenteritis and hospital-acquired rotavirus gastroenteritis among children aged less than 6 years in Japan: a retrospective, multicenter epidemiological survey.

BACKGROUND: Rotavirus is a leading worldwide cause of acute gastroenteritis in young children. This retrospective hospital-based study assessed the burden of rotavirus gastroenteritis in children younger than 6 years in Japan. METHODS: Children admitted to eight hospitals for acute gastroenteritis between 2008 and 2009 were identified from hospital admission databases. Diagnosis of acute gastroenteritis/rotavirus gastroenteritis and hospital-acquired rotavirus gastroenteritis was confirmed based on either the International Classification of Diseases and Related Health Problems 10th revision (ICD10) codes (intestinal infectious diseases [AA00-AA09] and rotavirus gastroenteritis [A08.0]) or from rapid rotavirus diagnostic test results. RESULTS: Of 13,767 hospitalized children, 11.9% (1,644), 4.8% (665) and 0.6% (81) were diagnosed with acute gastroenteritis, rotavirus gastroenteritis and hospital-acquired rotavirus gastroenteritis, respectively. Among acute gastroenteritis hospitalizations, 40.5% (665/1,644; ICD10 and rapid test) and 57.7% (645/1,118; rapid test only) were confirmed as rotavirus positive. Of 1,563 children with community-acquired acute gastroenteritis, 584 (37.4%) cases were confirmed as rotavirus positive. The median durations of hospitalization for all and community-acquired rotavirus gastroenteritis were 5.0 days (range: 2.0-133.0 days) and 5.0 days (range: 2.0-34.0 days), respectively. Among rotavirus gastroenteritis hospitalizations, 12.2% (81/665) of cases were hospital-acquired and the median duration of hospitalization was 10.0 days (range: 2.0-133.0 days). The median duration of additional hospitalization due to hospital-acquired rotavirus gastroenteritis was 3.0 days (range: 0-14 days). The overall incidence rate of hospital-acquired rotavirus gastroenteritis was 1.0 per 1,000 children hospital-days. The number of rotavirus gastroenteritis cases peaked between February and May in both 2008 and 2009, and the highest number of cases was reported in March 2008 (21.8%; 145/665). The highest number of rotavirus gastroenteritis hospitalizations (24.1%; 160/665) was observed in children aged 12-18 months. The proportion of hospital-acquired rotavirus gastroenteritis was higher in children aged below 18 months as compared to children at least 18 months of age (0.94 [95% CI: 0.71-1.21] vs. 0.39 [95% CI: 0.25-0.58]) and for children hospitalized for at least 5 days compared to those hospitalized for less than 5 days (0.91 [95% CI: 0.72-1.14] vs. 0.15 [95% CI: 0.05-0.32]). CONCLUSIONS: Both community- and hospital-acquired rotavirus gastroenteritis are significant public health problems in Japan. Data from this study justify the need for the introduction and implementation of rotavirus vaccination in the Japanese national immunization program. TRIAL REGISTRATION: ClinicalTrials.gov, NCT01202201.

Leukocytapheresis in pediatric patients with ulcerative colitis.

OBJECTIVE: Leukocytapheresis (LCAP) is a nonpharmacologic therapy that has recently been used to treat ulcerative colitis (UC). This multicenter open-label study prospectively assessed the efficacy and safety of LCAP in pediatric patients with UC. PATIENTS AND METHODS: Twenty-three patients ages 8 to 16 years with moderate (n = 19) to severe (n = 4) steroid-resistant UC were enrolled. One of 2 LCAP columns with different volumes (model EX and the half-volume model EI) was selected, according to body weight. LCAP was performed once per week for 5 consecutive weeks. Clinical and laboratory data were collected at predetermined time points. The primary endpoint was decreased stool frequency/hematochezia score, and secondary endpoints were clinical, laboratory, and endoscopic improvements. RESULTS: The stool frequency/hematochezia score decreased significantly from 4.5 ± 1.2 before treatment to 1.6 ± 1.9 after the fifth treatment. Clinical parameters, including stool frequency, presence of visible blood, abdominal pain, and body temperature, were significantly improved. Fecal calprotectin decreased significantly. Endoscopic findings evaluated using Matts score also improved (P < 0.01). The steroid dose decreased from 1.1 ± 0.4 mg/kg before treatment to 0.8 ± 0.5 mg/kg after treatment. There were no significant differences in changes between the EX and EI columns. The incidence of adverse effects was 61%, although none was serious. The most common adverse effects were decreased hematocrit and hemoglobin concentration. CONCLUSIONS: The present study showed that LCAP was well tolerated in children with UC, mostly moderate, and was as effective as in adults. The types of pediatric patients best suited to LCAP remain to be determined.