S. Cucchiara

Disorders of oesophageal motility in children with psychomotor retardation and gastro-oesophageal reflux.

A group of 25 children affected by different degrees of psychomotor retardation (severe (n=13); mild-moderate (n=12)) and symptoms suggesting gastro-oesophageal reflux (GOR) underwent oesophageal manometry and oesophageal pH monitoring. Of these patients, 21 (84%) were affected by GOR. In all children with severe brain damage and GOR (12/13), oesophageal manometry showed marked motility abnormalities that persisted after cure of GOR. In patients with minor retardation and GOR (9/12), oesophageal manometry showed normal motility or a less severe degree of oesophageal motor dysfunction which improved after curing the GOR. These results suggest that oesophageal motor dysfunction is a frequent occurrence in children affected by severe psychomotor retardation and GOR.

Idiopathic dilated cardiomyopathy associated with coeliac disease: the effect of a gluten-free diet on cardiac performance.

An increased incidence of coeliac disease has recently been reported in patients with idiopathic dilated cardiomyopathy. This report deals with three patients with idiopathic dilated cardiomyopathy and coeliac disease who underwent clinical and laboratory evaluation to establish the effect of a gluten-free diet on cardiac performance. Two patients observed the gluten-free diet regimen very strictly, and, after a 28-month follow-up period, showed an improvement in echocardiographic parameters as well as in cardiological features and quality of life, as evaluated by the Minnesota Living with Heart Failure questionnaire and the Gastrointestinal Symptom Rating Scale questionnaire. The third patient did not observe the gluten-free diet and presented a worsening in the echocardiographic parameters and cardiological symptoms which required supplementary drug therapy. These preliminary data appear to suggest that the gluten-free diet may have a beneficial effect on cardiac performance in patients with idiopathic dilated cardiomyopathy.

JC Viral reactivation in a pediatric patient with Crohn's disease.

This is a report concerning human polyomavirus JC (JCV) reactivation in a pediatric patient with Crohns disease (CD) during the treatment with 5-aminosalicylic acid (5-ASA), a non-steroidal anti-inflammatory drug (NSAID). We examined 9 bioptic samples from three different bowel districts (ileum, cecum, rectum) of this child. These samples were analyzed by Quantitative PCR (Q-PCR) to investigate the presence of JCV DNA. JCV DNA was detected in one rectum biopsy taken two months after 5-ASA treatment. Although our result must be validated in a larger group of subjects and with a longer follow-up period, it underlines the importance of JCV monitoring in CD patients.

Size and dynamics of mucosal and peripheral IL-17A+ T-cell pools in pediatric age, and their disturbance in celiac disease

Mucosal interleukin (IL)-17A–producing T cells contribute to protective antimicrobial responses and to epithelial barrier integrity; their role in celiac disease (CD) is debated. We analyzed the frequency and developmental dynamics of mucosal (intraepithelial lymphocytes (IEL)) and circulating (peripheral blood (PB)) IL-17A (T17) and/or interferon (IFN)-γ–producing (T1, T1/T17) T-cell populations in 86 pediatric controls and 116 age-matched CD patients upon phorbol myristate acetate/ionomycin or CD3/CD28 stimulation. T17 and T1/17 are physiologically present among IEL and PB populations, and their frequency is selectively and significantly reduced in CD IEL. The physiological age-dependent increase of Th17 IEL is also absent in CD, while IFN-γ–producing PB-T cells significantly accumulate with patients age. Finally, the amplitude of IL-17A+ and IFN-γ+ T-cell pools are significantly correlated in different individuals; this relationship only applies to CD4+ T cells in controls, while it involves also the CD4− counterpart in CD patients. In conclusion, both size and dynamics of mucosa-associated and circulating IL-17A+ T-cell pools are finely regulated in human pediatric subjects, and severely disturbed in CD. The impaired IL-17A+ IEL-T pool may negatively impact on epithelial barrier efficiency, and contribute to CD mucosa damage; the disturbed dynamics of circulating IL-17A+ and IFN-γ+ T-cell pools may be involved in the extraintestinal autoimmune manifestations associated with CD.

PP2 EFFICACY AND TOLERABILITY OF α-GALACTOSIDASE ON GAS RELATED SYMPTOMS IN PEDIATRIC IRRITABLE BOWEL SYNDROME. A RANDOMIZED, DOUBLE-BLIND, PLACEBO CONTROLLED TRIAL

Introduction: Bloating, abdominal distension and flatulence represent very frequent complaints in children with irritable bowel syndrome (IBS). These symptoms are frequently associated to excessive intestinal gas. Hence the reduction of gas production can be considered an effective therapeutic strategy. Alpha-Galactosidase has been shown to reduce gas production and related symptoms in adults. Aim: to evaluate the efficacy and tolerability of Alphagalactosidase on gas related symptoms in pediatric IBS patients. Patients and Methods: this was a single center, randomized, double-blind, placebo-controlled, parallel-group study performed in tertiary care setting. Fifty-two pediatric patients (32 female, median age 8 yrs, range 4-17) with IBS according to Rome III criteria were randomized to receive placebo (n = 25) or Alpha-galactosidase (n = 27) (Sinaire, Promefarm). Both treatments were given as drops or tablets according to body weight at the beginning of each of three meals for 2 weeks. Children were followed up two weeks after the end of treatment. Parent and/or selfassessment of the severity of gas related symptoms (bloating, flatulence, abdominal distension and abdominal spasms) were recorded 3 times daily during the treatment period using a validated visual score. The primary endpoint was reduction in the severity of bloating at the end of treatment compared to baseline. Secondary endpoints were reduction in the severity of other symptoms. As a measure of intestinal gas production, breath hydrogen concentration was measured at baseline and at the end of treatment. Results: α-galactosidase significantly reduced the severity of bloating (p = 0,023) and flatulence (p = 0,005) as compared with placebo. No significant differences were found for abdominal spasms and abdominal distension. The administration of Alpha-galactosidase had no significant effect on breath hydrogen excretion as compared with placebo (p = 0,54). The benefical effects of treatment tended to disappear in both groups at the end of follow-up. No treatmentrelated adverse events were reported during treatment. Conclusions: Although larger and longer trials are needed to confirm our results, Alpha-galattosidase looks a safe and effective agent for managing gas related symptoms in pediatric IBS.

Investigating the small bowel in pediatric Crohn's disease: Prospective comparative study between small intestine contrast ultrasonography and magnetic resonance imaging

Background: Magnetic resonance imaging (MRI) is considered the gold-standard to evaluate SB in pediatric Crohn’s disease (CD). However, MRI is expensive, requires a strong compliance and a considerable amount of oral contrast to distend intestinal lumen. Small intestine contrast ultrasonography (SICUS) is non-invasive, low cost and generally well tolerated by patients. Objectives: To compare the diagnostic accuracy of SICUS and MRI in detecting presence, site and extension of SB disease and in assessing strictures in pediatric CD. Methods: Pediatric pts with suspected or known CD were prospectively enrolled. All underwent SICUS, MRI and ileocolonoscopy, performed by blind different operators. The SB was subdivided into: jejunum, ileum, terminal ileum (TI). The statistic concordance (k) between the two techniques was calculated. For the TI sensitivity (SE) and specificity (SP) were also assessed, with endoscopy as reference standard. The one-way ANOVA was used to compare the disease extension (cm) in the different segments. Results:66 consecutive patientswere included. The overall k for the presence of lesions was=0.94 (ES 0.06; 95%CI 0.8–1. The k for segments was 0.67 (jejunum), 0.91 (ileum) and 0.91 (TI). SE and SP (%) of SICUS andMRI for TI lesions were 98, 100 and 93, 92, respectively. There was no difference (p ns) in the evaluation of disease extension between the two techniques. The k for SB strictures was 0.62. SE and SP (%) of SICUS andMRI for TI strictures were 100, 100 and 92, 87, respectively. MRI provided 7 false positive results. Conclusions: The diagnostic performance of SICUS is comparable to that ofMRI. SICUSmight represent afirst-line tool in pediatric CD, able to reduce costs and to post-pone or even avoid more invasive investigations.

CO2 ULTRASONOGRAPHIC ASSESSMENT OF COLONIC WALL IN PEDIATRIC ULCERATIVE COLITIS: COMPARATIVE STUDY WITH ILEO-COLONOSCOPY

Background and Aim: Stricturing is the most common complicated phenotype in children with Crohn’s disease (CD), but only few studies have described its course and there are no data on the efficacy of medical treatment. The purpose of this study was to retrospectively describe in pediatric stricturing CD the course and assess clinical and radiological response to medical therapy. Patients and Methods: 36 patients (pts) with stricturing CD (64% males, age range: 7.3–20.2 years, median 14.7), were identified by our department database. Records were reviewed for disease duration before detecting stenosis, location of strictures, type of medical treatment received, number of disease recurrences and hospitalizations. Pediatric Crohn’s disease Activity Index (PCDAI), need to change medical treatment or surgery, magnetic resonance imaging or small intestine contrast ultrasonography were used as outcomes and evaluated at 6, 12, 18 and 24 months after diagnosis of stenosis. Results: Strictures were ileal in 61% of pts, ileocolonic in 28% and colonic in 11%; 6 pts (17%) also had proximal jejunal stenosis. Thirteen pts (36%) had a stricturing disease at the time of CD diagnosis, while 64% developed it at the follow-up (2.48±4.12 years after CD diagnosis). Cumulative risk for developing stenosis was 22%, 27% and 28% at 12, 18 and 24 months, respectively. At baseline, 89% of pts underwent medical treatment, while 11% had surgical resection: in a multivariate analysis, only ileal stenosis and severe abdominal pain significantly differed between the two groups (p: 0.05 and p: 0.006, respectively). At 6, 12, 18, and 24 months, 53%, 50%, 42%, and 35% had a complete response to medical treatment, respectively; whereas 34%, 43%, 40%, and 34% had a partial response, defined as a radiological evidence of stenosis requiring a change of their medical therapy. Overall, 44% were unresponsive to medical therapy and required surgery during 24 months followup; responders and non-responders did not statistically differ for clinical variables such as duration of disease, location of stenosis, mean PCDAI at the beginning of the therapy and type of medical treatment. Conclusions: A stricturing phenotype is not uncommon at the diagnosis of CD in children. Medical therapy seems to be poorly effective in avoiding intestinal resection and common clinical variables are not of value in discriminating between responder and non responders to medical therapy. Prospective studies are needed to define the optimal management strategy of stricturing CD and to identify predictive factors of medical treatment failure.

24 GASTROINTESTINAL (GI) MOTILITY, DUODENOGASTRIC REFLUX (DGR) AND GASTRIC EMPTYING (GE) IN CHILDREN WITH CHRONIC VOMITING

We evaluated GI motility by means of a perfused catheter system, DGR, as assessed by Bile Salts (BS) output in gastric aspirates, and GE of a milk labeled formula (% of emptying at 1 hr) in 11 patients (pts) with unexplained chronic vomiting. (Apts), in 8 pts with protracted gastroesophageal reflux (GER) disease (Bpts) and in 7 symptomatic controls (Cpts). Mean ± SD age (months) was respectively 44.2±37.7, 18.1±11.2, 20.4±14.4. In 9 Apts and 5 Bpts we found GI manometric abnormalities none of which were seen in Cpts: a) fasting and/or fed antral (and/or duodenal) hypomotility; b) abnormal propagation or configuration of interdigestive motor complexes (IMC); c) bursts of non propagated duodenal or jejunal motility; d) sustained fasting and/or fed phasic activity incoordinated with adjacent gut segments. Both A and B pts had BS fasting recovery significantly higher than Cpts during the various phases of IMC (mean group values (mg/ml): 1.52 (A), 1.12 (B), 0.36 (C), p < 0.05) and a significant delay of GE (A: 32.8±8.9%; B: 34.4±9.8%) as compared to Cpts (64.5±5.3%, p< 0.05, mean±SD). Highest degrees of gastric BS output and of delayed GE were associated with the most marked GI motility dysfunctions in both A and B pts. Conclusions: 1) children with chronic unexplained vomiting may exhibit, at GI manometry, disordered gut motility patterns; 2) the latter seem to be associated with increased DGR and delayed GE; 3) severe GER disease shows diffuse dysmotllity of upper GI tract.

ESOPHAGEAL MOTILITY (EM) IN BRAIN DAMAGED PATIENTS (PTS)

Oropharyngeal Dysphagia(OPD)is a common feature in PTS with brain damage. We performed esophageal manometry in 13 PTS(mean age:11.3 months)with neurological handicaps ranging from spastic tetraparesis with severe brain atrophy to only moderate psychomotor mental retardation, in order to assess the role of the EM in the mechanism; of the OPD. All 13 PTS complained of swallowing disorders and failure to thrive, 10 also had vomiting and 9 had pulmonary aspiration, too. All 13 but one had Gastroesophageal Reflux(GER)and 8/10 esophagitis. In PTS with severe brain damage(9/13)esophageal manometry showed a marked Upper Esophageal Sphincter(UES)dysmotility(incomplete relaxation and/or incoordinated activity)and an abnormal motility of the proximal esophagus. Symptoms and EM abnormalities were persistent after cure of GER. In PTS with minor neurological signs(4/13)esophageal manometry showed a normal EM and less severe degrees of UES dysmotility. This latter defect and symptomatology were not persistent after 4-12 months follow-up. In conclusion:Difficulty in swallowing, aspiration of food materials and failure to thrive in some PTS with neurological impairement may be caused by disorders of UES and esophageal motility.