Very early onset inflammatory bowel disease in a South Asian country where inflammatory bowel disease is emerging: a distinct clinical phenotype from later onset disease.

BACKGROUND/AIMS: Information on pediatric inflammatory bowel disease (PIBD) and very early onset IBD (VEOIBD) are sparse in India, where IBD is emerging. We aimed to evaluate characteristics of VEOIBD and later onset PIBD (LO-PIBD) in India. METHODS: We performed retrospective analysis of a large, prospectively maintained IBD registry. PIBD was divided in to VEOIBD ( < 6 years) and LO-PIBD (6-17 years). Demographic data, disease characteristics and treatment were compared between the PIBD groups and with other Asian/Western studies as well as the adult patients of the registry. RESULTS: Of 3,752 IBD patients, 292 (7.8%) had PIBD (0-17 years) (175 Crohn's disease [CD], 113 ulcerative colitis [UC], 4 IBD-undifferentiated; 22 VEOIBD [7.5%], and 270 LO-PIBD [92.5%]). VEOIBD patients had more severe disease compared to LO-PIBD in both UC (P= 0.003) and CD (P< 0.001). Familial IBD was more common in VEOIBD (13.6%) compared to LO-PIBD (9.2%). Ileal disease (L1) was an independent risk factor for diagnostic delay in pediatric CD. Diagnostic delay ( > 6 months) was significantly lower in VEOIBD (40.9%) than in LO-PIBD (78.8%) (P< 0.001). Compared to other Asian and Western studies, extensive UC (72.5%) and complicated CD (stricturing/penetrating: 42.7%) were relatively more common. Perianal CD was relatively less frequent (7.4%). PIBD had a significantly higher number of complicated and ileal CD and extensive UC comparison to adult cohort of the registry. CONCLUSIONS: VEOIBD has more aggressive phenotype than LO-PIBD. Disease appears distinct from other Asian and Western studies and adult onset disease, with more complicated CD and extensive UC.

Functional dyspepsia in children: A study of pathophysiological factors.

BACKGROUND AND AIM: Functional dyspepsia (FD) is common in children, and treatment targeted towards the altered pathophysiology can improve outcome. We evaluated FD children for abnormality of gastric accommodation and emptying, psychological stressors (PS), Helicobacter pylori (HP) infection, and post-infectious FD. METHODS: Diagnosis of FD was based on ROME III criteria. Clinical evaluation including dyspeptic symptom scoring and assessment for PS was performed. Satiety drink test for gastric accommodation, gastroscopy with biopsy for HP infection, and solid meal gastric emptying were performed. Sixty-seven healthy children were enrolled for assessing PS and satiety drink test. RESULTS: Fifty-five FD children (33 boys, age 12 [6-18] years) with symptoms for 4 (2-48) months and dyspeptic score of 5 (1-13) were enrolled. PS were more common in FD than in controls (46/55 vs 9/67; P < 0.001). Median satiety drink volume was 360 mL (180-1320 mL); no patients had satiety drink volume of < 5th centile of healthy children. The frequency (98% vs 85%; P = 0.01) and severity (65 [10-175] vs 50 [5-130]; P < 0.001) of postprandial symptoms were higher in FD than in controls. Of the postprandial symptoms, pain (20.3% vs 0%; P = 0.000) was present only in FD. Delayed gastric emptying was present in 6.5%, HP infection in 11%, and post-infectious FD in 13% cases. Etiological factor was identified in 87% children, with 20% having multiple factors. CONCLUSIONS: Abnormality of gastric sensorimotor function is seen in one-fourth of FD cases. HP infection and post-infectious FD are present in 11% and 13% cases, respectively.

Pancreas Divisum Increases the Risk of Recurrent Acute Pancreatitis in Patients with rs12338 Polymorphism in the Cathepsin B Gene.

OBJECTIVES: Pancreas divisum (PD) as a cause of pancreatitis has been debated. In this study, we report the association of multiple gene polymorphisms on the risk of RAP in the presence of PD. DESIGN: We enrolled 687 individuals (167 IRAP, 276 ICP, and 244 unrelated healthy controls) from May 2015 to September 2016. Patients were divided into those with/without PD. Associations between the significantly prevalent SNPs and IRAP/ICP in the presence of PD were evaluated. Clinical data were analyzed using Mann-Whitney U/Chi-square test. Effect size of association of SNPs with IRAP/ICP was expressed as odds ratio (OR) (95% CI). Gene-gene interaction was assessed by transheterozygosity analyses. Bonferroni-corrected two-tailed "p" value of ≤ 0.01 was considered statistically significant. RESULTS: Thirty-three (19.8%) and 82 (29.7%) patients with IRAP and ICP, respectively, had PD. Among the patients with IRAP, duration of disease was significantly shorter in those with PD compared to those without (mean [95% CI] duration: 1.6 (1.3-1.9) vs 2.7 (2.3-3.1) years; p = 0.005). There were no differences in gender, race, and diabetes among patients with/without PD in IRAP/ICP groups. Mean (95% CI) pancreatic duct diameter (mm) was significantly higher in the presence of PD in patients with both IRAP [1.6 (1.4-1.9) v/s 1.29 (1.2-1.4); p = 0.03)] and ICP [5.2 (4.5-5.9) v/s 4.5 (3.9-5.1); p = 0.02]. CTSB (rs12338) polymorphisms were significantly associated with IRAP [OR (95% CI) 2.44 (1.41-4.22); p = 0.001] among patients with PD. No association was observed with ICP. Transheterozygosity analysis did not show any significant associations of combination of SNPs with IRAP in the presence of PD. CONCLUSION: Risk of RAP due to PD increases in patients with rs12338 polymorphism in the cathepsin B gene.

Genetic Evaluation of Children with Idiopathic Recurrent Acute Pancreatitis.

OBJECTIVES: Several genetic risk factors have been identified in adults with idiopathic acute recurrent pancreatitis (IARP). However, the literature regarding the genetics of IARP is sparse in children. In this study, we aimed to analyze the genetic risk factors in children with IARP. METHODS: All children (< 18 years) with ARP from January 2015 to May 2018 were prospectively enrolled in the study. Children with a known cause of ARP like obstructive, toxic/metabolic, and autoimmune were excluded from the final analysis. Children with IARP underwent genetic testing for mutations/polymorphisms in genes known to predispose to pancreatitis including cationic trypsinogen protease serine 1 (PRSS1), serine protease inhibitor Kazal type 1 (SPINK1), cystic fibrosis transmembrane conductance regulator gene (CFTR), chymotrypsin C (CTRC), claudin-2 (CLDN2) and cathepsin B (CTSB). RESULTS: A total of 239 children (116 boys, 10.3 ± 3.7 years) were enrolled during the study period. Of these, 204 (85.35%) children were identified as IARP. The mean age of symptom onset and the number of pancreatitis episodes were 8.3 ± 3.7 years and 3.3 ± 1.8, respectively. A family history of pancreatitis was noted in 4.6% children. Mutations/polymorphisms in at least 1 gene were identified in 89.5% (129/144) children including SPINK1 in 41.9%, PRSS1 (rs10273639) in 58.2%, CTRC in 25.6%, CTSB in 54.9%, CLDN2 in 72.9%, and CFTR in 2.3%. There was no significant incidence of genetic mutations/polymorphisms in IARP with or without pancreas divisum (95.7 vs 88.4%; p = 0.467). CONCLUSIONS: Genetic alterations are present in the majority of the children with IARP. The incidence of genetic mutations is similar in children with or without pancreas divisum.

Outcome of radiological interventions in pediatric gastrointestinal diseases: A large tertiary center experience.

BACKGROUND: Interventional radiology (IR) is an indispensable component of multidisciplinary care in various gastrointestinal (GI) diseases. The literature on safety and utility of IR is limited in children. OBJECTIVES: In this study, we aim to analyze the outcomes of IR in various pediatric GI diseases. METHODS: The data of children (≤18 years) who underwent radiological interventions for GI disorders (2009-2017) were analyzed, retrospectively. The indications for interventions included vascular (Budd Chiari syndrome [BCS], pseudoaneurysm) and nonvascular (pancreatic fluid collections [PFCs], cholangitis and anastomotic biliary strictures). The outcomes of radiological interventions, including success and adverse events, were assessed. RESULTS: A total of 93 children (mean age 13.45 ± 4.09 years) underwent radiological interventions for vascular (chronic BCS = 14, pseudoaneurysm = 28) or nonvascular (PFCs = 33, hepaticojejunostomy strictures or leaks = 12, cholangitis = 6) indications. Of 33 children who underwent drainage of PFCs, clinical success was noticed in 32 children during a mean follow-up of 32.4 ± 21.66 months; 11 children with persistent external pancreatic fistula were managed with endoscopic pancreatic ductal stenting (8 children) and internalization of transgastric drain (3 children). In children who underwent hepatic vein or inferior vena cava stenting for BCS, mean stent patency was 78.57% during a follow-up of 24.1 ± 13.78 months. In children with pseudoaneurysms, angioembolization was successfully performed in 92.8% patients. Re-bleeding was noticed in two children, one of whom required reintervention. In children who underwent percutaneous transhepatic biliary drainage, resolution of anastomotic strictures was noticed in all during a follow-up of 36.1 ± 13.73 months. CONCLUSION: Interventional radiology is safe and effective in the management of various pediatric GI diseases.

Disconnected Pancreatic Duct in Children With Walled OFF Necrosis: Impact on Outcomes of Endoscopic Drainage.

OBJECTIVES: Disconnected pancreatic duct syndrome (DPDS) is frequently encountered in cases with walled off necrosis (WON). The impact of DPDS on the outcomes of pancreatic fluid collections (PFCs) is not well known. In this study, we aim to evaluate the incidence of DPDS and its clinical impact on the outcomes of endoscopic ultrasound (EUS)-guided drainage of PFC in children. METHODS: All children with symptomatic WON who underwent EUS-guided drainage using metal stents were included in the study. At 4 weeks, pancreatic ductal anatomy was evaluated, and metal stents removed. All the children were followed at regular intervals and evaluated for the recurrence of PFC and the development of new-onset diabetes. RESULTS: A total of 32 children (28 boys, median age 15 years) underwent EUS-guided drainage of WON. Resolution of WON was documented in all children at 4 weeks. Pancreatic ductal anatomy using magnetic resonance retrograde cholangiopancreatography and endoscopic retrograde pancreatography was available in 30 (93.7%) children. Of these, DPDS was documented in 25 (83.3%) children including proximal disconnection in 12 and distal disconnection in 13 children. Recurrent PFC and new-onset diabetes were found in 5 (20%) and 2 (8%) children with DPDS, respectively. Of the 5 recurrences of PFC, endoscopic reintervention was required in 3 children. CONCLUSIONS: Majority of the children with DPDS do not develop a symptomatic recurrence of PFC after the removal of cystogastric stents. DPDS may be a risk factor for the development of new-onset diabetes. However, future prospective studies are needed.

Outcome of peroral endoscopic myotomy in children with achalasia.

BACKGROUND AND AIMS: Achalasia cardia is rare in children and optimum endoscopic management options are not well known. Peroral endoscopic myotomy (POEM) is a novel treatment modality for achalasia with excellent results in adult patients. The long-term outcomes of POEM are not well known in children. In this study, we aim to evaluate the outcome of POEM in children with idiopathic achalasia. METHODS: We analyzed the data of children (≤ 18 years) diagnosed with achalasia from September 2013 to January 2018. Technical success, clinical success, and adverse events were assessed. Post-POEM, gastroesophageal reflux (GER) was assessed with 24-h pH-impedance study and esophagogastroduodenoscopy. RESULTS: A total of 44 children (boys-23, girls-21) with mean age of 14.5 ± 3.41 years (4-18) were diagnosed with achalasia during the study period. Of these, 43 children underwent POEM. The subtypes of achalasia according to Chicago classification were type I-11, type II-29, type III-2, and unclassified-2. Eighteen children (40.9%) had history of prior treatment. POEM was successfully performed in 43 children (technical success-97.72%). Intra-operative adverse events occurred in 11 (25.6%) children including retroperitoneal CO2 (7), capnoperitoneum (3), and mucosal injury (1). Clinical success at 1, 2, 3, and 4 years' follow-up was 92.8%, 94.4%, 92.3%, and 83.3%, respectively. Erosive esophagitis was detected in 55% (11/20) children. On 24-h pH study, GER was detected in 53.8% (7/13) children. CONCLUSION: POEM is a safe, effective, and durable treatment for achalasia in children. However, GER is a potential concern and should be evaluated in prospective studies before adopting POEM for the management of achalasia in children.

Assessment of stool frequency and colonic transit time in Indian children with functional constipation and healthy controls.

INTRODUCTION: Indian adults have higher stool frequency and shorter colonic transit time compared to the Western population. Colonic transit time has not been studied well in Indian children. We aimed to compare colonic transit time in normal and constipated children. METHODS: In this prospective study, stool characteristics and colonic transit time by radio-opaque markers were studied in healthy children (group A, n = 39) and functional constipation patients (group B, n = 61). Twenty radio-opaque markers were ingested per orally at 0, 12, and 24 h followed by a single abdominal X-ray at 36 h. Total and segmental colonic transit times were calculated using the standard formula. RESULTS: Stool frequency per week and consistency were significantly different between group A (9 [2.5-17] years) vs. group B (4.5 [2-14] years), 7 (7-14) vs.1 (1-2), and Bristol type 4 (3-5) vs. type 2 (1-3). Total colonic transit time of groups A and B was 16.2 (0.6-36) vs. 22.8 (1.8-35.4) hours; p = 0.003. Ninety-fifth percentile (upper limit of normal) cutoff derived from group A was 31.8 h. Ninety-two percent of group B had colonic transit < 95th percentile of normal healthy children. Despite 8% with colonic transit > 95th percentile, all group B patients responded well to standard therapy with laxatives. CONCLUSION: Indian children have significantly higher stool frequency and shorter colonic transit time, which are different compared to the reported figures from the West. Most of the Indian children with functional constipation had normal colonic transit time.

Diagnosis of Hirschsprung's disease in children: Preliminary evaluation of a novel endoscopic technique for rectal biopsy.

BACKGROUND AND AIM: The diagnosis of Hirschsprung's disease (HD) relies on anorectal manometry and rectal biopsy. The role of endoscopic biopsy is uncertain for the diagnosis of HD in children. In this study, we evaluated the adequacy of biopsies procured by endoscopic mucosal resection (EMR) for the diagnosis of HD. METHODS: Consecutive children with suspected HD from January 2013 to January 2018 were enrolled in the study. EMR was performed using the standard band ligation device at a distance of about 3 cm from dentate line in rectum. All samples were assessed macroscopically and microscopically. An adequate sample was defined as those measuring >3 mm and including adequate submucosa. RESULTS: A total of 132 children underwent evaluation for constipation in the study period. Of these, 10 children (median age, 4.25 years) underwent EMR using the band ligation device for the evaluation of HD. EMR was performed with and without submucosal lifting injection in four and six children, respectively. All the samples were adequate macroscopically (>3 mm). Absence of ganglion cells was noted in six children. Of these, three children underwent full-thickness rectal biopsy followed by surgery. Three children did not undergo surgery. Ganglion cells were identified in four children, thereby excluding the diagnosis of HD. CONCLUSION: Rectal biopsy using EMR with a band ligation device is feasible, safe, and provides adequate sample for the evaluation of HD in children.

Nutrient drink test: Normative values in Indian children.

BACKGROUND: Nutrient drink test (NDT) is a simple, non-invasive method to assess gastric function including accommodation. However, data on normal satiety drink volume (SDV) in children is scanty with no information about postprandial symptoms (PPS). Our aims were to establish normal values of NDT in healthy children and evaluate its correlation with age, gender, and anthropometry. METHODS: Six- to 18-year-old healthy children underwent the NDT. The nutrient drink (0.94 kcal/mL) was given at a constant rate of 15 mL/min in 6-12-year-old subjects and at 30 mL/min in 13-18-year-old subjects till satiety score of 5 was reached. Postprandial symptoms (30 min) of fullness, nausea, bloating, and pain were scored using a visual analogue scale (0-100 mm) individually and as aggregate score. RESULTS: Sixty-seven children (40 boys, age 12 [6-18 years]) were enrolled. Median SDV was 360 [180-960 mL], higher in 13-18-year-olds in comparison to 6-12-year-old children (360 [240-1002] vs. 300 [148-960] mL; p=0.005). SDV showed significant correlation with age, weight, and height. SDV was higher in boys than girls (450 [240-1074] vs. 330 [240-480] mL; p=0.02) in the older children (13-18 y), but it was similar in the younger children. Mild fullness (40 [0-80]) was the only PPS seen in 85% children and none had pain. PPS were not different between boys and girls or younger and older children. CONCLUSION: The study provides normative data of SDV and PPS by NDT in 6-18-year-old children. SDV correlated with age and was higher in adolescent boys than girls.

ß-Blocker therapy ameliorates hypersplenism due to portal hypertension in children.

BACKGROUND/PURPOSE: Thrombocytopenia due to hypersplenism precludes percutaneous liver biopsy in many cases of chronic liver disease (CLD). The aim of this study was to assess the efficacy of propranolol in correcting platelet counts (>100,000/mm(3)) to ensure percutaneous liver biopsy in children with CLD. METHODS: From January 2005 to December 2012, 51 consecutive children (mean age 11.5 ± 3.0 years, 34 boys) with CLD who needed liver biopsy but could not be done due to hypersplenism-related thrombocytopenia (platelets <100,000/mm(3) and/or total leukocyte counts <4,000/mm(3) with splenomegaly) were recruited and given a 4-week trial of long-acting propranolol (1.5-2 mg/kg/day). Hemodynamic parameters and splenic artery hemodynamics by Doppler ultrasound were recorded before and after the propranolol trial. Response to therapy was defined as improvement of platelet counts to ≥10(5)/mm(3). RESULTS: Thirty-two (62.7%) children responded to propranolol therapy and their mean platelet counts increased from 57.5 ± 13.0 × 10(3) to 140.7 ± 43.3 × 10(3)/mm(3), p = 0.0001. Liver biopsy could be done in 29. While comparing responders with non-responders, baseline spleen size (7.4 ± 3.3 vs. 12.7 ± 4.5 cm, p = 0.0001) and platelet counts (57.5 ± 13.0 × 10(3) vs. 39.5 ± 14.5 × 10(3), p = 0.0001) were found to be significant. ROC curve suggested a cut-off value of ≤8.5 cm of spleen and ≥53,000 platelets as predictors of response. With propranolol, mean arterial pressure and spleen size reduced (p < 0.05) and splenic artery resistance increased significantly (p = 0.005) in responders. CONCLUSIONS: Propranolol corrects thrombocytopenia and makes liver biopsy possible in almost two-thirds of cases by reducing splenic sequestration through splenic artery vasoconstriction. The baseline spleen size and platelet counts determine the effectiveness of therapy. A trial of ß-blocker is worth carrying out in cases where liver biopsy is contraindicated due to hypersplenism-related thrombocytopenia.

Severe heart failure, dilated cardiomyopathy and pulmonary haemosiderosis in coeliac disease: report of two cases.

Coeliac disease (CD) is a chronic inflammatory, multi-system disorder with protean manifestations which has been linked to various auto-immune-mediated disorders. Dilated cardiomyopathy (DCM) is a rare extra-intestinal manifestation that is being recognised increasingly in patients with CD. Two cases of CD are described, an 18-year-old boy and a 13-year-old girl, both of whom presented with rapid onset of congestive heart failure and severe left ventricular systolic dysfunction. Upper limb venous thrombosis and recurrent haemoptysis secondary to pulmonary haemosiderosis in the second case were the other unusual features. The importance of CD screening of patients with DCM and pulmonary haemosiderosis is emphasised.

Anasarca as the initial presentation of juvenile polymyositis: an uncommon occurrence.

Polymyositis is uncommon in childhood. Unlike dermatomyositis, which is common in pediatric age group, skin involvement is lacking in polymyositis. We report an 8-year-old boy who presented with anasarca as the initial complaint. This presentation has been rarely reported before in the pediatric literature.

Imatinib has adverse effect on growth in children with chronic myeloid leukemia.

BACKGROUND: Long-term adverse effects of Imatinib in children with chronic myeloid leukemia (CML) are uncertain. The aim was to study the effect of imatinib on growth in children with CML. PROCEDURE: Children ≤13 years of age at diagnosis were enrolled retrospectively, from 2004 to 2011, from a single center in India. Patients who received imatinib for >1 year were included for growth assessment. Height standard deviation scores (SDS) were derived from WHO-AnthroPlus, a global growth monitoring tool. RESULTS: Thirty-four children received imatinib. Twenty children fulfilled the criteria for assessment of growth. Median age was 10 years (range: 2-13). Of 20 children, 13 were prepubertal at commencement of imatinib. The mean duration of imatinib in 20 children was 61.3 ± 16.2 months (range: 31-83). No patient was treated with a second-generation tyrosine kinase inhibitor or a stem cell transplant. Highly significant reduction in height SDS's was observed (P = 0.002 at 5th year). Children who started imatinib therapy after the onset of puberty were immune to this adverse effect (P = 0.448 and 0.003 at 5th year of treatment for pubertal and prepubertal children, respectively). The 5-year survival probability of 33 children who received imatinib in chronic phase was 80% with a median survival time of 60 months (mean: 70.2; 95% CI: 60-80.5). CONCLUSIONS: Growth retardation is a significant adverse effect of imatinib in children with CML. The failure to gain appropriate height was most discernible when imatinib was initiated in the prepubertal period. Etiology and remedial measures need to be investigated.