Minimal endoscopic sphincterotomy followed by papillary balloon dilation to relieve choledocholithiasis in a 6-year-old girl with hereditary spherocytosis.

A 6-year-old girl previously diagnosed with hereditary spherocytosis was admitted to our hospital with gallstones and cholangitis. Endoscopic retrograde cholangiopancreatography (ERCP) was performed, and fluoroscopy revealed a dilated common bile duct (CBD) without evident stones, possibly due to spontaneous excretion through the papilla of Vater. A 7-French plastic stent was inserted into the CBD. After the procedure, a marked increase in pancreatic enzyme levels was observed, and she was diagnosed with post-ERCP pancreatitis (PEP). Stent placement could have been a cause of pancreatitis; therefore, we removed the stent. Subsequently, recovery from pancreatitis was confirmed, although she suddenly complained of abdominal pain and was diagnosed with choledocholithiasis recurrence. ERCP was repeated, and fluoroscopy revealed a dilated CBD with a stone. A minimal endoscopic sphincterotomy (EST) was performed to reduce the risk of PEP, and a biliary dilation balloon placed across the papilla was gradually inflated until the waist of the balloon disappeared. Stones were extracted using a retrieval balloon catheter. The abdominal pain resolved immediately, and the patient recovered without developing PEP. To our knowledge, this is the first case report of a pediatric patient treated with minimal EST followed by papillary balloon dilation for choledocholithiasis.

Utility of a rapid assay for prostaglandin E-major urinary metabolite as a biomarker in pediatric ulcerative colitis.

Prostaglandin E-major urinary metabolite (PGE-MUM) is a urinary biomarker reflecting ulcerative colitis (UC) activity. This prospective observational study aimed to evaluate the usefulness of PGE-MUM via rapid chemiluminescent enzyme immunoassay in detecting endoscopic remission (ER) and histologic remission (HR) in pediatric UC (6-16 years) in comparison with fecal calprotectin (FCP). ER and HR were defined as Mayo endoscopic score (MES) of 0 and Matts' histological grades (Matts) of 1 or 2, respectively. A total of 104 UC and 39 functional gastrointestinal disorder (FGID) were analyzed. PGE-MUM levels were significantly higher in the UC group than in the FGID group (P < 0.001). FCP levels were significantly elevated in the group without ER and HR than in the group with ER and HR (P < 0.001 and P = 0.001), whereas PGE-MUM levels were significantly higher in the group without ER compared to the group with ER (P < 0.001). No significant differences were noted in the AUCs for PGE-MUM and FCP in detecting ER and HR. Although PGE-MUM was inferior to FCP for the detection of HR, it might have the potential for application as a biomarker of endoscopic activity in pediatric UC owing to its noninvasive and rapid method.

Accuracy of Transperineal Ultrasonography for Assessing Rectal Lesions in Paediatric Ulcerative Colitis: A Prospective Study.

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 < 0.05]. RWT and RWF were independent predictors of UC endoscopic activity, showing sensitivity of 95.8% and specificity of 100% with RWT ≥ 4.5 mm and positive RWF. The concordance rates between TPUS and TAUS findings in MES 2-3 were moderate to fair, whereas those in MES 0-1 were fair to poor. The concordance rates between ultrasonic examiners were good for both TAUS and TPUS. 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.

Expert consensus on vaccination in patients with inflammatory bowel disease in Japan.

Immunosuppressive therapies can affect the immune response to or safety of vaccination in patients with inflammatory bowel disease (IBD). The appropriateness of vaccination should be assessed prior to the initiation of IBD treatment because patients with IBD frequently undergo continuous treatment with immunosuppressive drugs. This consensus was developed to support the decision-making process regarding appropriate vaccination for pediatric and adult patients with IBD and physicians by providing critical information according to the published literature and expert consensus about vaccine-preventable diseases (VPDs) [excluding cervical cancer and coronavirus disease 2019 (COVID-19)] in Japan. This consensus includes 19 important clinical questions (CQs) on the following 4 topics: VPDs (6 CQs), live attenuated vaccines (2 CQs), inactivated vaccines (6 CQs), and vaccination for pregnancy, childbirth, and breastfeeding (5 CQs). These topics and CQs were selected under unified consensus by the members of a committee on intractable diseases with support by a Health and Labour Sciences Research Grant. Physicians should provide necessary information on VPDs to their patients with IBD and carefully manage these patients' IBD if various risk factors for the development or worsening of VPDs are present. This consensus will facilitate informed and shared decision-making in daily IBD clinical practice.

Both fecal calprotectin and fecal immunochemical tests are useful in children with inflammatory bowel disease.

BACKGROUND: Noninvasive biomarkers of intestinal inflammation can reduce the number of endoscopies in children with inflammatory bowel disease (IBD). This study aimed to prospectively investigate the usefulness of fecal calprotectin (FCP) and fecal immunochemical test (FIT) in pediatric IBD. METHODS: Patients aged 6-17 years who underwent ileocolonoscopy for established or suspected IBD were eligible for this study. Fecal samples for FCP and FIT were collected before colonoscopy. RESULTS: A total of 251 samples were analyzed: 88 from ulcerative colitis (UC), 74 from Crohn's disease (CD), 75 from healthy controls (HC), and 14 from children with functional gastrointestinal disorders and normal colonoscopy (NC). At IBD diagnosis, both FCP and FIT were significantly higher in the newly diagnosed UC/CD group than in the HC/NC group (P < 0.001). The optimal cutoffs of FCP and FIT to predict IBD diagnosis were 217 mg/kg and 87 ng/mL, respectively. Patients without mucosal healing (MH) showed higher FCP and FIT than those with MH in both UC and CD (P < 0.001). The FCP increased exponentially as the endoscopic activity score increased. The optimal cutoff values of FCP and FIT for predicting MH were 161 mg/kg and 106 ng/mL for UC and 367 mg/kg and 57 ng/mL for CD, respectively. FCP showed better specificity than the FIT. Patients with CD and normal ileocolonoscopy had elevated FCP during active small intestinal inflammation. CONCLUSIONS: Both FCP and FIT correlate well with endoscopic activity in pediatric patients with IBD. The FCP is a superior marker for predicting MH.

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.

Expression of Oncogenic Molecules in Pediatric Ulcerative Colitis.

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.

Novel pediatric granulomatosis with polyangiitis with a marked bloody pericardial effusion and bloody stool: a case report.

BACKGROUND: Granulomatosis with polyangiitis (GPA) is a syndrome of refractory vasculitis involving the upper respiratory tract, lungs, kidneys, and systemic small and medium-sized arteries that affects all age groups. No pediatric case with a bloody pericardial effusion resulting in cardiac tamponade and co-existing hematochezia has been reported. CASE PRESENTATION: A 14-year-old boy was referred for evaluation of prolonged fever, chest pain, and intermittent hematochezia. Diagnostic imaging showed a prominent pericardial effusion. Immediately after admission, his systolic blood pressure decreased. Emergent pericardiocentesis resulted in aspiration of a massive amount of bloody pericardial fluid. This was diagnosed as cardiac tamponade because his blood pressure recovered immediately after the drainage. The patient had an elevated serine proteinase 3-anti-neutrophil cytoplasmic antibody (PR3-ANCA) level on serological examination. Head MRI showed thickening of nasal and sinusoidal mucosa and a cystic mass in the left sphenoid sinus. After ruling out malignancy based on the cytology of the effusion, chest MRI, and gallium scintigraphy, total colonoscopy showed multiple irregular-shaped aphthae from the right transverse colon to the cecum on the contralateral side of the mesenteric attachments. Biopsy specimens of aphthous lesions confirmed necrotizing granulomatous inflammation. A diagnosis of GPA was made based on these findings, and oral prednisolone (PSL) and azathioprine were started. The hematochezia disappeared rapidly, and no recurrence of pericardial effusion was seen after PSL tapering was completed. The PR3-ANCA level decreased into the normal range immediately after the initial therapy. CONCLUSIONS: Pericarditis is a common cardiac complication of GPA, but there have been no reports of resultant cardiac tamponade. This is the first case of pediatric GPA with cardiac and gastrointestinal complications preceding the common symptoms such as respiratory or renal symptoms. A case of pediatric GPA with hematochezia is also extremely rare. In conclusion, serial measurement of ANCA levels is important in patients with persistent fever and bloody stool, such as in inflammatory bowel disease, to make the diagnosis of a vasculitic syndrome.

Long-Term Durability of Infliximab for Pediatric Ulcerative Colitis: A Retrospective Data Review in a Tertiary Children's Hospital in Japan.

PURPOSE: The long-term efficacy and safety of infliximab (IFX) in children with ulcerative colitis (UC) have not been well-evaluated. Here, we reviewed the long-term durability and safety of IFX in our single center pediatric cohort with UC. METHODS: This retrospective study included 20 children with UC who were administered IFX. RESULTS: For induction, 5 mg/kg IFX was administered at weeks 0, 2, and 6, followed by every 8 weeks for maintenance. The dose and interval of IFX were adjusted depending on clinical decisions. Corticosteroid (CS)-free remission without dose escalation (DE) occurred in 30% and 25% of patients at weeks 30 and 54, respectively. Patients who achieved CS-free remission without DE at week 30 sustained long-term IFX treatment without colectomy. However, one-third of the patients discontinued IFX treatment because of a primary nonresponse, and one-third experienced secondary loss of response (sLOR). IFX durability was higher in patients administered IFX plus azathioprine for >6 months. Four of five patients with very early onset UC had a primary nonresponse. Infusion reactions (IRs) occurred in 10 patients, resulting in discontinuation of IFX in four of these patients. No severe opportunistic infections occurred, except in one patient who developed acute focal bacterial nephritis. Three patients developed psoriasis-like lesions. CONCLUSION: IFX is relatively safe and effective for children with UC. Clinical remission at week 30 was associated with long-term durability of colectomy-free IFX treatment. However, approximately two-thirds of the patients were unable to continue IFX therapy because of primary nonresponse, sLOR, IRs, and other side effects.

Effectiveness of Biological Agents in the Treatment of Pediatric Patients with Crohn's Disease and Anal Fistulae.

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.

Eradication therapy for Helicobacter pylori infection based on the antimicrobial susceptibility test in children: A single-center study over 12 years.

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 < 0.05). According to the results of the antimicrobial susceptibility test, we prescribed effective antibiotics, and this resulted in a primary eradication rate of 97.7%. CONCLUSIONS: We suggest that antimicrobial susceptibility testing can significantly improve rates of primary eradication of H. pylori infection.

Efficacy of Helicobacter pylori Eradication Therapy on Platelet Recovery in Pediatric Immune Thrombocytopenic Purpura-Case Series and a Systematic Review.

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.

A novel segmental absence of intestinal musculature with small intestinal stenosis: a case report.

BACKGROUND: Segmental absence of intestinal musculature (SAIM) is a rare cause of intestinal obstruction and perforation due to partial or complete defects in the intestinal muscularis propria in neonates and is occasionally observed in adulthood. CASE PRESENTATION: The first case of small intestinal stenosis derived from SAIM, which was difficult to differentiate from Crohn's disease (CD), is reported. A 4-year-old girl presented with abdominal pain, anemia, and a positive fecal occult blood test. She was initially diagnosed with CD and started on treatment. Because her gastrointestinal symptoms persisted, her previous pediatricians tried to carry out capsule endoscopy, but it was not possible because the patency capsule was retained. Therefore, she was referred to our institute and re-evaluated. The patency capsule examination was repeated to re-evaluate small intestinal passage, but it stagnated again. Abdominal ultrasonography showed a poorly deformable intestinal tract that narrowed rapidly from the dilated segment and had a thin wall with an irregular laminar structure. In addition, unlike the typical ultrasonic CD findings, the power Doppler signal enhancement at the intestinal wall and "creeping fat sign" were not found. The patient was referred for laparoscopic observation to pediatric surgeons, who confirmed a prominently dilated intestinal tract 40 cm proximal to the ileocecal valve, which was resected. Histopathological findings showed longitudinal muscle hypoplasia of the resected, dilated intestinal tract and fat replacement of the muscle layer. At the stenosis site, the muscle layer was fibrotic and showed incomplete muscle arrangement. Because of these findings, she was diagnosed with SAIM. After the surgical treatment, no gastrointestinal symptoms relapsed, and the fecal occult blood test has remained negative for 2 years. Moreover, 8 months after surgery, double-balloon endoscopy showed no abnormalities, such as a longitudinal ulcer and cobblestone appearance. CONCLUSIONS: In the present case, SAIM involved not only intestinal ileus and perforation, but also small intestinal stenosis. Although no other reports have demonstrated the usefulness of abdominal ultrasonography for the diagnosis of SAIM, the present report suggests that ultrasonography may be useful for differentiating SAIM from CD by close observation of the area around the small intestinal stenosis.

Ultrasonographic study of intestinal Doppler blood flow in infantile non-IgE-mediated gastrointestinal food allergy.

BACKGROUND: Although non-IgE-mediated gastrointestinal food allergy has increased rapidly in Japan, a small number of reports has evaluated B-mode and Doppler ultrasonographic findings in the acute phase of infantile gastrointestinal milk allergy. The aim of the present study was to compare the diagnostic utility of ultrasonographic findings and laboratory allergic data in non-IgE-mediated infantile gastrointestinal milk allergy. METHODS: Sixteen cases of active non-IgE-mediated infantile gastrointestinal milk allergy, diagnosed by food elimination tests and oral food challenge tests (OFCTs) (group A), 15 cases of acute viral gastroenteritis (AGE) (group B), and 15 controls (group C) were enrolled. 1) B-mode abdominal ultrasound findings, 2) laboratory allergic data including eosinophil counts (Eos), serum IgE, and the antigen-specific lymphocyte proliferation test (ALPT) against milk protein, and 3) vessel density (VD) indirectly quantified by gastrointestinal Doppler flow at jejunum, ileum, and sigmoid colonic mucosae were evaluated and compared among the groups. RESULTS: In the small intestine, wall thickening, dilation, mesenteric thickening, and poor peristalsis were found in 100%, 62.5%, 93.7%, and 100%, respectively, in group A. Eos, IgE, ALPT, and VD were positive in 25.0%, 0%, 87.5%, and 100%, respectively, in group A. Small intestinal VD was significantly greater in group A than in groups B (jejunum p < .001; ileum p < .001) and C (jejunum p < .001; ileum p < .001), with no significant differences between groups B and C (jejunum: p = .74; ileum: p = .73). CONCLUSIONS: Abdominal Doppler ultrasonography and small intestinal VD at symptomatic state can support the diagnosis and evaluation of non-IgE-mediated infantile gastrointestinal milk allergy with symptoms of vomiting, diarrhea, and failure to thrive.

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.

5-Aminosalicylate intolerance causing exacerbation in pediatric ulcerative colitis.

BACKGROUND: 5-Aminosalicylate (5-ASA) is widely used as the first-line drug for ulcerative colitis (UC). 5-ASA is mostly a safe and effective drug, but it can bring about exacerbation due to 5-ASA intolerance. 5-ASA intolerance can be confusing and it can mislead physicians into considering unnecessary treatment escalation, including corticosteroid (CS), biologics, or even surgery. In spite of the clinical importance of 5-ASA intolerance, there have been few studies on its incidence, clinical features, and diagnosis. METHODS: In order to evaluate the incidence, characteristic symptoms, disease course, and laboratory data of children with 5-ASA intolerance, we retrospectively reviewed the medical records of 80 children with UC. RESULTS: Eleven of 80 children (13.8%) with UC were diagnosed with 5-ASA intolerance. The median time between the initiation of 5-ASA and the onset of 5-ASA intolerance was 10 days (range, 4-20 days) in patients not receiving CS. Drug-induced lymphocyte stimulation test (DLST) was performed in 10 patients, and was positive in eight. C-reactive protein (CRP) increased significantly when exacerbation of colitis symptoms occurred. CONCLUSIONS: The incidence of 5-ASA intolerance was relatively high. Besides the challenge test, elevation of CRP and positive DLST appeared to support the diagnosis of 5-ASA intolerance.

Prolonged tacrolimus for pediatric gastrointestinal disorder: Double-edged sword?

BACKGROUND: Although tacrolimus (TAC) can induce remission in children with refractory inflammatory bowel disease (IBD) or autoimmune gastroenteropathy (AGE), its use in maintenance therapy remains controversial. The aim of this study was to investigate the potential nephrotoxic nature of prolonged TAC use. METHODS: This retrospective study reviewed children with gastrointestinal disorder who underwent kidney biopsy for the evaluation of renal damage during TAC therapy for >1 year. The clinical and histological features of renal damage were evaluated in this single-institution cohort. RESULTS: Eighteen of 121 children with IBD and two children with AGE followed at a national children hospital in Tokyo, Japan, received TAC between August 2006 and April 2013. Among them, five (Crohn's disease, n = 3; autoimmune gastropathy, n = 1; autoimmune enteropathy, n = 1) received TAC for >1 year, and underwent kidney biopsy. All five had achieved remission on TAC, but had histological evidence of chronic nephrotoxicity. Renal damage in one patient with relatively low TAC trough level remained mild. Estimated glomerular filtration rate (eGFR) at the time of kidney biopsy was lower than at the initiation of TAC in all four available patients. Among them, eGFR improved in one patient after the decrease or discontinuation of TAC. CONCLUSIONS: TAC appeared to be effective in children with refractory gastrointestinal disorder, but long-term use seems to cause irreversible renal damage. Rigorous monitoring of eGFR and kidney biopsy in selected cases should be considered for the proper adjustment of TAC.

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.

Assessment of the Family History of Patients With Ulcerative Colitis at a Single Center in Japan.

OBJECTIVES: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.