Comparative Study of Two Cohorts of Newly Diagnosed Crohn's Disease Demonstrates Change in Therapeutic Strategies.

BACKGROUND: There has been a paradigm shift in the treatment of Crohn's disease (CD) involving the rapid introduction of biologics and/or immunomodulators after diagnosis. We wished to assess whether this was applied to patients with newly diagnosed CD in a tertiary inflammatory bowel disease referral centre in Israel. METHODS: Newly diagnosed CD patients were stratified into 2 groups: the early group was diagnosed between 2005 and 2007 and the late group was diagnosed between 2010 and 2012. Baseline demographics, medical and surgical treatments, disease course and complications during those 2 periods were analyzed. RESULTS: Each group included 60 patients. Significantly higher rates of immunomodulators and biologics were administered to patients in the late group compared to the early group (81.7 and 36.7% compared to 56.7 and 18.3%, p = 0.004 and p = 0.021, respectively). On the other hand, steroid therapy was less prevalent in the late (36.7%) group compared to that of the early group (56.7%), p = 0.059. Medical and surgical CD outcomes, including exacerbations/hospitalizations and surgeries, were comparable for both groups. CONCLUSIONS: There was a change in treatment strategy between 2005-2007 and 2010-2012, as reflected in higher proportions of biologics/immunomodulators for patients with newly diagnosed CD. This was associated with a steroid-sparing effect.

Polyposis syndromes in children and adolescents: a case series data analysis.

BACKGROUND: Polyposis syndromes in children are distinct entities clinically and pathologically. These syndromes have multiple genetic characteristics, with development of polyps at various sites of the gastrointestinal (GI) tract, and are associated with an increased risk of colon cancer. They are relatively rare, and have mostly been characterized in the adult population, whereas little epidemiologic data have been reported in children. AIMS: The aim of this study was to summarize the pediatric experience collected over a period of 11 years on polyposis syndromes in three major Israeli tertiary centers. PATIENTS AND METHODS: Medical records of children below 18 years old and their families, diagnosed with polyposis syndromes between 1999 and 2010, were reviewed. The data included disease presentation, genetic profile, surveillance, and treatment. RESULTS: Fifty patients with polyposis syndromes were identified. The most frequent syndrome was familial adenomatous polyposis (FAP) in 33 children (66%), of whom 25 children (75.7%) had a known mutation. The mean age at presentation was 10.6±3.9 years (range 4-17 years). Most children were examined because of a family history of a polyposis syndrome (42 children, 84%). Among symptomatic children (32 children), the most frequent complaint was rectal bleeding (42%), followed by abdominal pain (22%), intussusception (10%), and diarrhea (4%). The youngest symptomatic patient was 4 years old at presentation, with rectal bleeding.All patients underwent multiple colonoscopies and upper GI endoscopies according to specific guidelines. Thirteen children underwent colonic surgery (39%); nine children had FAP. Adenocarcinoma of the colon was diagnosed in a 12.5-year-old child. CONCLUSION: In this cohort study, FAP was the most common type of polyposis syndrome diagnosed in this pediatric population. Colon cancer was present at the onset of symptoms in a 12.5-year-old patient with FAP. We therefore recommend strict adherence to the hereditary GI cancer guidelines to prevent morbidity and mortality in FAP and other inherited polyposis syndromes.

Propofol for pediatric colonoscopy: the experience of a large, tertiary care pediatric hospital.

Successful colonoscopy includes full visualization of the terminal ileum, especially in inflammatory bowel disease when ileal biopsy is essential. In children, higher levels of anxiety and lack of cooperation often necessitate a deeper level of sedation. The aim of this study was to evaluate the effectiveness of propofol compared with midazolam and fentanyl for colonoscopy, and in accomplishing ileal and cecal intubation in particular. This was a retrospective cohort study comparing the rates of successful colonoscopy in patients receiving propofol with those receiving midazolam/fentanyl. Complete, successful, colonoscopy to the terminal ileum was achieved in 78% of propofol patients compared with 66% of the midazolam/fentanyl group (P=0.004). Endoscopy reaching the cecum, but not the terminal ileum, was achieved in 78% of propofol patients and 66% of midazolam/fentanyl patients. The use of propofol was associated with a statistically significant increase in the rate of successful colonoscopy reaching the terminal ileum.

FOXP3 expression in duodenal mucosa in pediatric patients with celiac disease.

OBJECTIVE: It was the aim of this study to evaluate the number of 2 lymphoid subpopulations, CD8(+) cells and FOXP3(+), in the duodenum mucosa from pediatric celiac patients. METHODS: Tissue sections prepared from paraffin-embedded biopsies of the descending duodenum of 61 celiac patients with Marsh grade 1 (M1), M2 and M3 disease and biopsies from 21 age-matched non-celiac (NC) patients were immunohistostained with anti-CD8 or FOXP3 antibodies. RESULTS: The histological Marsh grade correlated with the mean number of FOXP3(+) cells in the lamina propria (LP) mucosa (8.9 ± 1.1, 6.8 ± 2.4, 24.5 ± 2.6 and 31.1 ± 2.8 for NC, M1, M2 and M3 biopsies, respectively; p < 0.001). Using a cutoff point of 15 cells, 95% of NC and 88% of M1 biopsies had a mean of <15 FOXP3(+) cells compared with 14% for M2 and 13% for M3 biopsies. The number of FOXP3(+) cells in the epithelial mucosa also correlated with transglutaminase type 2 serum levels from the celiac patients. Unlike the FOXP3(+) cells, CD8(+) lymphocytes were present in both LP and surface epithelial mucosa and significantly different only in the LP mucosa of the M2 and M3 groups. CONCLUSION: The number of FOXP3(+) cells is substantially increased in the mucosa of celiac patients at advanced stages. Characterization of the activity of these cells in celiac and in other inflammatory bowel diseases will enable us to understand the significance of these cells in celiac disease.

Endoscopic ultrasonography in pediatric patients with gastrointestinal disorders.

BACKGROUND: Endoscopic ultrasound is a diagnostic tool for evaluation of gastrointestinal diseases in adults, but in children the use of endoscopic ultrasound is limited. This study retrospectively evaluates endoscopic ultrasound indications in, safety in, and impact on children. PATIENTS AND METHODS: We reviewed the data of all of the pediatric patients (<18 years old) that underwent endoscopic ultrasound in our institution. The main goal was to evaluate the impact of endoscopic ultrasound in this patient population. Significant impact was defined as a new diagnosis or treatment attributed to the endoscopic ultrasound examination. RESULTS: Thirty-two children (21 boys, 11 girls) at mean age 12 +/- 5 years; (range = 1.5-18 years) underwent endoscopic ultrasound during a period of 6 years. The pancreas and biliary tract were examined in 19 children, esophagus in 8, and the stomach and rectum in 2 children each. Only 1 child had endoscopic ultrasound for duodenal indication. The indications in the pancreas and biliary tract group were recurrent pancreatitis in 9 children, cyst or mass in 6 children, and obstructive jaundice in 4 children. Indications in the esophagus group were stenosis in 4 children, and suspected duplication and esophageal mass in 2 children each. We used conscious sedation in 18 children and unconscious sedation in 12. Two children underwent endoscopic ultrasound with no anesthesia at all. In 7 cases, endoscopic ultrasound-guided fine-needle aspiration was performed. The procedure was successful in all of the patients with no complications. Endoscopic ultrasound changed the diagnosis or therapy in 14 cases. CONCLUSIONS: Endoscopic ultrasound is an effective tool in the evaluation of pediatric gastrointestinal patients, mostly with pancreatobiliary or esophageal disorders. Endoscopic ultrasound is a safe procedure with a significant impact in almost half of the children examined.

[Percutaneous endoscopic gastrostomy (PEG) in children: indications, the procedure, outcomes, short and long-term complications].

BACKGROUND: Feeding through tubes placed in the intestine is a useful way of nutritional support in a patient who is unable to eat but has a well functioning gastrointestinal system. Till 1980, the acceptable technique to place a gastrostomy tube was surgical. However, in the past twenty years percutaneous endoscopic gastrostomy (PEG) has replaced surgical gastrostomy in most settings. GOALS: In this study we explored the indications, the age of the patients, the conditions in which the procedure took place and its outcome in children. The study aimed to investigate the effectiveness of this method in children. METHODS: The data was gathered retrospectively according to information found in the files and a questionnaire the parents answered. Fifty-two children from the Tel Aviv Medical Center and from the Sheba Medical Center who underwent a PEG procedure were studied. The data gathered from the study included age, gender, origin, sequence of the procedure, indications, place, performers, complications and the effectiveness of the method according to parents' satisfaction and weight of the patient. In addition, the following parameters were studied: type of anesthesia, sort of antibiotics that were provided, number of cases in which enteral nutrition was given permanently or temporarily, type of formula that was given and the way it was introduced, number of failures and fundoplications. RESULTS: Mean age of the children was 5.4 years. Ninety six percent of the procedures succeeded. The most common indications were failure to thrive (35%) and neurological disorders. In 56% of cases the performer was a gastroenterologist alone. When the procedures were performed by gastroenterologists, a lower rate of complications was seen than with a gastroenterologist and a surgeon (20.8% vs. 52.6% accordingly). In 57% of the children there were no complications observed. In addition, most of the complications which were observed were minor (abdominal pain, nausea and vomiting and reflux). CONCLUSIONS: According to this study we concluded that PEG is a minimally invasive technique, associated with a low rate of severe complications and provides significant support for children who need enteral nutrition.

Beta-adrenergic hyperresponsiveness in compensated hypothyroidism associated with Down syndrome.

Although compensated hypothyroidism (CH) is the most common thyroid impairment in Down syndrome (DS), its pathogenesis remains elusive. Because primary gonadal failure is another DS-associated endocrinopathy, we hypothesized that an impaired signal-transduction pathway shared by several organs may provide a unifying explanation for both endocrinopathies. We assessed two possible transduction-pathway components associated with CH in DS: the G-protein adenylate-cyclase (AC) system and beta-adrenergic responsiveness, previously reported to be enhanced in DS fibroblasts. Twenty-one DS patients and 14 control subjects were studied. Peripheral mononuclear cells (PMCs) were incubated with G-protein modulators [prostaglandin E1 (PGE1) and cholera toxin (CTx)], an AC stimulator (forskolin), and a beta-adrenergic agonist (isoproterenol), and cAMP levels were determined. All participants had normal plasma thyroid hormone levels, but 11 of the DS patients had elevated TSH levels (hTSH), whereas in the 10 others, they were normal (nTSH). cAMP levels in response to forskolin, PGE1, and CTx were similar in all groups, whereas isoproterenol-stimulated cAMP levels were significantly higher in the hTSH group than in the nTSH group and control subjects (45 +/- 30 versus 22 +/- 9 and 21 +/- 9 pmol . 10(6) cells(-1) . 10 min(-1), respectively; p = 0.02). Four patients in the DS hTSH subgroup had impaired sexual development. We found hyperresponsiveness of PMCs to a beta-adrenergic agonist in a subgroup of DS patients with CH. If this observation is applicable to the thyroid gland, then it may reflect a mechanism in which negative effects on cell growth or responsiveness to TSH lead to CH.