G. Di Nardo

Chronic intestinal pseudo-obstruction in children and adults: diagnosis and therapeutic options

Chronic intestinal pseudo‐obstruction (CIPO) represents the most severe form of gastrointestinal dysmotility with debilitating and potentially lethal consequences. Symptoms can be non‐specific, and result in this condition being diagnosed incorrectly or too late with consequences for morbidity and even mortality.

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.

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.

PA44 AN UNUSUAL GUT BLEEDING IN CHILDHOOD SUCCESSFULLY TREATED WITH OCTREOTIDE

Objective: Menetrier’s disease, also called hypoproteinemic hypertrophic gastropathy, is a rare, acquired, premalignant disorder of the stomach. It is generally characterized by giant hypertrophic folds that most often involve the fundus, excessive mucus secretion, decreased acid secretion (hypochlorhydria), and hypoproteinemia due to selective loss of serum proteins across the gastric mucosa. Aims and methods: A four year old boy was referred to our Pediatric Gastroenterology and Liver Unit because of iron deficiency anemia. The child had been healthy since his birth; no illness during the delivery or the neonatal period were accounted. He had been breastfed till 12 months of age, his physical and psychological development was unremarkable and his growth curves were within the normal ranges. At medical history, it was reported that his grandfather suffered from Menetrier’s disease. Therefore, on suspicion of chronic obscure gastrointestinal bleeding, we performed upper gastrointestinal tract (GI) endoscopy which disclosed markedly thickened gastric folds with nodularity, erythema, and exudate involving the proximal stomach (corpus and fundus); the antrum and pylorus did not show pathological features. Histological specimens of the stomach obtained by multiple superficial cold forceps biopsies showed only foveolar hyperplasia and dilatation of some glands. Helicobacter pylori was not found. Cytomegalovirus (CMV) PCR on gastric aspiration, serum and urine did not show the presence of viral load. Results: After one month, we re-performed upper GI endoscopy in order to obtain a wider sample for histological examination by jumbo forceps. At this time, the pathologist identified marked foveolar hyperplasia and elongation of gastric pits, cystic dilatation of gastric gland in the deeper part of the mucosa, moderate atrophy of fundic glands; in the lamina propria there was no inflammation, but marked dilatation and congestion of small vessels, and diffuse edema has been observed. These findings suggested the diagnosis of Menetrier’s disease, and the child was thus treated with Octreotide longacting release (LAR) which brought to clinical amelioration of the anemia. Conclusion: The cause of Menetrier’s disease is unknown, although in children infection by CMV and by Helicobacter Pylori have been implicated. Classical symptoms include epigastric pain, vomiting, edema, anorexia, and weight loss. In this case of pediatric Menetrier’s disease, the only clinical feature was iron deficiency anemia, probably due to congested small vessel leakage. We might speculate that this child had not expressed yet all the other features of the disease, such as the protein-loss syndrome, because of his early diagnosis. The medical treatment of Menetrier’s disease consists of Octreotide administration, which is a somatostatin analogue, and in our case successfully controlled hemorrhage from gastric lesions.

CO15 DIAGNOSTIC USEFULNESS OF SINGLE BALLOON ENTEROSCOPY IN CHILDREN WITH GASTROINTESTINAL DISORDERS UNDEFINED AT CONVENTIONAL ENDOSCOPY

IFX for remission 7 were still in remission, 5 restarted biologic therapy (3 Adalimumab, 2 IFX), 1 underwent ileal resection. No serious adverse events or malignancies were reported. Conclusions: In our cohort of IBD pts, IFX maintenance therapy was a durable and effective treatment over a 3-year period in children with CD, it appeared also an effective therapeutic option to avoid or postpone colectomy in UC pts.

PP23 ARGON PLASMA COAGULATOR IN A 2-MONTH-OLD CHILD WITH TRACHEO-OESOPHAGEAL FISTULA

A 2 month-old boy was admitted to the authors’ hospital because of regurgitation and persistent cough during breastfeeding. A chest X-ray examination and a barium esophagogram disclosed small amounts of barium passing in the trachea, suggesting a tracheoesophageal fistula (TEF). Bronchoscopy combined with upper gastrointestinal (GI) endoscopy performed with the patient under general anesthesia confirmed the fistula. The TEF was treated by injection of 1 ml Glubran 2 from the esophageal side. A nasogastric tube was placed for feedings, and 7 days later, a barium esophagogram showed a reduction of caliber but not complete closure of the TEF. Unsuccessful fistula obliteration with Glubran was attributed to technical difficulties in catheterization of the fistula orifice, mainly resulting from its close proximity to the upper esophageal sphincter and to its small caliber. Therefore, an argon plasma coagulator (APC) probe with a circumferentially oriented nozzle was used from the esophageal side as an alternative technique to fulgurate the residual fistula orifice (see video). A nasogastric tube was placed for feedings. Oral feeding was started 7 days later when a barium esophagogram confirmed complete fistula closure. At the 2-year follow-up visit, the boy was asymptomatic, and the barium esophagogram was negative. This report describes a case in which esophagoscopy gave a clear view of the fistula due to its direction from esophagus to trachea. Complete fistula obliteration was not obtained with Glubran. However, APC was successfully used to close the residual fistula orifice. The authors suggest that APC can be used as an alternative endoscopic technique to repair TEF when other techniques fail.