[Capsule endoscopy in children: which are the best indications?]. / Quelles indications pour l'endoscopie du grêle par vidéocapsule en pédiatrie?

BACKGROUND AND STUDY AIMS: Capsule endoscopy (CE) is a novel and noninvasive means of investigating the small bowel. In children, the best CE indications have not yet been fully appraised. The aim of this study was to evaluate the diagnostic yield of CE in different pediatric pathologies. PATIENTS AND METHODS: We retrospectively reviewed every CE performed in children in two French pediatric hospitals between March 2002 and June 2009. Seventy-nine CEs were performed on 70 children (mean age, 10.6 years; range, 2.2-18.0); 52 boys and 18 girls. The indications were iron deficiency anemia (24%), obscure gastrointestinal bleeding (14%), polyposis syndromes (16%), suspected Crohn disease (15%), unresponsive Crohn disease (10%), graft-versus-host disease (10%), and other (10%). RESULTS: Of the 79 CEs, 69 reached the cecum (87%). Only one occlusion occurred in a case of stenosing Crohn disease, requiring surgical removal. In addition, technical difficulties led to an incomplete small bowel study in 12 cases (16%). The CE showed small bowel lesions in 42 cases (53%). The diagnostic yield was 27% in obscure gastrointestinal bleeding, 37% in iron-deficiency anemia, 42% in suspected Crohn disease, 88% in unresponsive Crohn disease, 62% in polyposis syndromes, and 88% in graft-versus-host disease. CONCLUSION: In children, CE is well tolerated and can be performed in children as young as 2.2 years of age. Its diagnostic yield is highest in polyposis syndromes, unresponsive Crohn disease, and graft-versus-host disease.

Treatments for pediatric achalasia: Heller myotomy or pneumatic dilatation?

AIM: The treatment of achalasia consists of reducing distal esophageal obstruction by either Heller myotomy surgery or endoscopic pneumatic dilatation. The aim of the present study was to evaluate the short- and middle-term results of these procedures in children. METHODOLOGY: For technical reasons, children under six years old (n=8) were treated by surgery only, whereas patients over six years old (n=14) were treated by either Heller myotomy or pneumatic dilatation. RESULTS: Of the children aged under six years, 75% were symptom-free at six months and 83% at 24 months of follow-up. Of the patients aged over six years, complete remission was achieved by Heller myotomy in 44.5% vs. 55.5% by pneumatic dilatation after six months, and in 40% vs. 65%, respectively, after 24 months. Both pneumatic dilatation and Heller myotomy showed significant rates of failure. CONCLUSION: These results suggest that pneumatic dilatation may be considered a primary treatment in children over six years old. Also, where necessary, Heller myotomy and pneumatic dilatation may be used as complementary treatments.

[Hemorrhagic ascites revealing duodenal duplication]. / Une ascite hémorragique révélant une duplication duodénale.

Duodenal duplication is a rare congenital disorder of the gastrointestinal tract. The presentation is highly variable. We report a case of duodenal duplication presenting with hemorrhagic ascites in a 3-month-old girl. The diagnosis of duodenal duplication can be made preoperatively by resonance magnetic imaging. Surgical resection of the duplication was performed. Microscopic examination of the specimen confirmed the duodenal duplication. To our knowledge, this is the 1st reported case of hemorrhagic ascites caused by duodenal duplication and demonstrated by resonance magnetic imaging.

Prevention of relapse by mesalazine (Pentasa) in pediatric Crohn's disease: a multicenter, double-blind, randomized, placebo-controlled trial.

AIM: This study aimed to test the efficacy of mesalazine in maintaining remission in pediatric Crohn's disease (CD) following successful flare-up treatment. METHODS: In this double-blind, randomized, placebo-controlled trial, 122 patients received either mesalazine 50mg/kg per day (n=60) or placebo (n=62) for one year. Treatment allocation was stratified according to flare-up treatment (nutrition or medication alone). Recruitment was carried out over two periods, as the first period's results showed a trend favoring mesalazine. Relapse was defined as a Harvey-Bradshaw score more than or equal to 5. Time to relapse was analyzed using the Cox model. RESULTS: The one-year relapse rate was 57% (n=29) and 63% (n=35) in the mesalazine and placebo groups, respectively. We demonstrated a twofold lower relapse risk (P<0.02) in patients taking mesalazine in the medication stratum (first recruitment period), and a twofold higher risk in patients taking mesalazine in the nutrition stratum (second recruitment period), compared with the other groups. None of the children's characteristics, which differed across the two recruitment periods, accounted for the between-period variation in mesalazine efficacy. One serious adverse event was reported in each treatment group. CONCLUSION: Overall, mesalazine does not appear to be an effective maintenance treatment in pediatric CD.

Long-term outcome, growth and digestive function in children 2 to 18 years after intestinal transplantation.

OBJECTIVE: Small bowel (SB) transplantation (Tx), long considered a rescue therapy for patients with intestinal failure, is now a well recognised alternative treatment strategy to parental nutrition (PN). In this retrospective study, we analysed graft functions in 31 children after SBTx with a follow-up of 2-18 years (median 7 years). PATIENTS: Twelve children had isolated SBTx, 19 had combined liver-SBTx and 17 received an additional colon graft. Growth, nutritional markers, stool balance studies, endoscopy and graft histology were recorded every 2-3 years post-Tx. RESULTS: All children were weaned from PN after Tx and 26 children remained PN-free. Enteral nutrition was required for 14/31 (45%) patients at 2 years post-Tx. All children had high dietary energy intakes. The degree of steatorrhoea was fairly constant, with fat and energy absorption rates of 84-89%. Growth parameters revealed at transplantation a mean height Z-score of -1.17. After Tx, two-thirds of children had normal growth, whereas in one-third, Z-scores remained lower than -2, concomitant to a delayed puberty. Adult height was normal in 5/6. Endoscopy and histology analyses were normal in asymptomatic patients. Chronic rejection occurred only in non-compliant patients. Five intestinal grafts were removed 2.5-8 years post-Tx for acute or chronic rejection. CONCLUSIONS: This series indicates that long-term intestinal autonomy for up to 18 years is possible in the majority of patients after SBTx. Subnormal energy absorption and moderate steatorrhoea were often compensated for by hyperphagia, allowing normal growth and attainment of adult height. Long-term compliance is an important pre-requisite for long-term graft function.

[Rotavirus: an ubiquitous infection?]. / Rotavirus: une infection ubiquitaire?

Rotavirus is the most frequent virus found in childhood gastroenteritis. A rotavirus viremia is observed in 19 to 63 % of cases, for three days at the beginning of infection. Then, rotavirus can reach several organs as liver (hepatitis in 1/3 of case), nervous central system (2 % of encephalitis could be linked to rotavirus), or more infrequently mesenteric lymph nodes, lung or heart. However, the link between rotavirus and systemic manifestations has not been well established. Further studies are necessary to confirm the role of rotavirus in these organ's lesions.

[Medication in infectious acute diarrhea in children]. / Traitement médicamenteux des diarrhées aiguëis du nourrisson et de l'enfant.

Acute infectious diarrhea in children remain still a frequent cause of morbidity. 50 % of them are due to rotavirus. Oral rehydration therapy and early realimentation have drastically reduced their mortality and morbidity. Beside oral or eventually IV rehydration therapy no medication has proven its efficacy based on the main HMO criteria (reduction of over 30 % of the stool output) except racecadotril and loperamide which is contre-indicated for the last one in children less than 2 years old. Other medications such as silicates or some probiotics have shown efficacy on diarrhea duration or stool consistency but not on stool output. They have so no formal indication in infectious diarrhea and should be considered as "comfort" treatment. Antibiotics, beside their indication in shigella, cholera and amibiasis could be used in invasive diarrhea in some debilating conditions or infants less than 3 months.

Efficacy of methotrexate in pediatric Crohn's disease: a French multicenter study.

BACKGROUND: Immunosuppressors play a major role in maintaining remission in Crohn's disease (CD). In patients who do not tolerate or escape therapy with azathioprine (AZA)/6-mercaptopurine, there is a marked need for other immunosuppressive drugs. The aim of the present study was to evaluate the efficacy and safety of methotrexate (MTX) in children with active CD. METHODS: In a retrospective multicenter (n = 3) study, the efficacy of MTX to induce complete remission or a clinical improvement was analyzed in 61 children with active CD. RESULTS: CD was diagnosed at a mean age of 11.1 +/- 2.3 years, and MTX was introduced 3.1 +/- 2.2 years after diagnosis. Indications to use MTX were a nonresponse to or relapse under AZA (n = 42) or AZA intolerance/toxicity (n = 19). MTX improved or induced complete remission in 49 patients (80%), of whom 18 (29.5%) relapsed after 13 +/- 10 months of treatment. Under MTX medication, complete remission was observed in 39%, 49%, and 45% at 3, 6, and 12 months, respectively. Follow-up over at least 24 months in 11 children confirmed a sustained remission on MTX monotherapy up to 40 months. Adverse reactions were observed in 14 patients (24%), requiring discontinuation of MTX in 6 children (10%) (liver enzyme elevation, n = 2; varicella-zoster, n = 1; nausea, n = 3). MTX allowed corticosteroid discontinuation in 36 patients. CONCLUSIONS: MTX improved the clinical course in most pediatric CD patients who escaped or did not tolerate AZA. Short-time toxicity of MTX resulted in drug discontinuation in <10%. These data point to a beneficial and safe use of MTX in the treatment of pediatric CD.

Factors influencing outcome after intestinal transplantation in children.

We evaluated 131 patients (6 months-14 years) who experienced 21 deaths before listing, 11 continuing on the waiting list, 38 well on home parenteral nutrition, 6 off parenteral nutrition and 59 transplanted (20 girls) aged 2.5 to 15 years, (18 >7 years). They received cadaveric isolated intestine (ITx, n = 31) or liver-small bowel (LITx, n = 32), including right colon (n = 43; 23 LITx) for short bowel (n = 19), enteropathy (n = 20), Hirschsprung (n = 14), or pseudo-obstruction (n = 6). Treatment included tacrolimus, steroids, azathioprine, or interleukin-2 blockers. After 6 months to 10.5 years, the patient and graft survivals were 75% and 54%. Sixteen patients (10 LITx) died within 3 months from surgery (n = 3), bacterial (n = 5) or fungal (n = 6) sepsis, or posttransplant lymphoproliferative disorder (n = 2). Rejection occurred in 27 patients, including 10 steroid-resistant episodes requiring antilymphoglobulins. The grafts were removed due to uncontrolled rejection in seven ITx recipients. Surgical complications were observed in 38 recipients (25 LSBTx) within 2 months, including bacterial (n = 22) or fungal (n = 11) sepsis, cytomegalovirus disease (n=12), adenovirus (n = 11), or posttransplant lymphoproliferative disorder (n = 12). Forty-two children (19 LSBTx) are alive. Weaning from parenteral nutrition was achieved after 42 days (median). Factors related to death or graft loss were pre-Tx surgery (P < .01), pseudo-obstruction (P < .01), age over 7 years (P < .03), fungal sepsis (P < .03), steroid resistant rejection (P < .05), hospitalized versus home patient (P < .01), and retransplantation (P < .05). Colon transplant did not affect the outcome. Interleukin-2 blockers improved isolated ITx (P < .05). Early referral and close monitoring of intestinal failure and related disorders are mandatory to achieve successful ITx.

Severe dysimmune cytopenia in children treated with tacrolimus after organ transplantation.

Rare cases of dysimmune phenomena after solid organ transplantation were described in the past. In the present series, we describe six children who developed severe dysimmune anemia or thrombocytopenia while treated with tacrolimus after liver or small bowel transplantation. All patients were off steroids or under low doses alternate day steroid medication when dysimmune cytopenia developed. All patients had positive anti-platelets antibodies and/or Coombs' positive anemia. Therapy was successful in all six patients with a rapid response to corticosteroids in three children, and to anti-CD20 monoclonal antibodies (rituximab) in the three others. The pathogenesis of these rare dysimmune/autoimmune disorders might be related to the interference of tacrolimus with T-cell functions and/or the endogenous control mechanisms of T-lymphocyte activation and down-regulation. Although rare, these complications must be known when discussing protocols of immunosuppression.

Reflux in esophageal atresia, tracheoesophageal cleft, and esophagocoloplasty: Bianchi's procedure as an alternative approach.

PURPOSE: Fundoplication has been used successfully to treat gastroesophageal reflux (GER) in the pediatric population. Although successful in many patients, there is a significant risk of complications and failure, especially in high-risk patients such as those with certain types of associated anomalies, diffuse motility disorders, chronic pulmonary disease, neurological impairment, and young infants. However, the results are poorer with children with severe pathologic lesion associated to reflux: tracheoesophageal cleft, esophagocoloplasty, and esophageal atresia (EA) with severe dysmotricity. In neurologically impaired children with neuromuscular incoordination and GER, Bianchi has proposed total esophagogastric dissociation (TED). The authors report the use of esophagogastric or esocologastric dissociation to control reflux in children with severe GER in other situations, such as EA, burn esophageal lesions having led to coloplasty and severe esotracheal cleft. METHODS: The authors reviewed the patients operated on for an esogastric or cologastric disconnection between 1997 and 2002. It is a single center retrospective study. The initial diagnosis, previous surgical procedure, postoperative course, and follow-up results were studied. RESULTS: Between September 1999 and June 2003, 13 TEDs were performed in 6 boys and 7 girls. The mean age for TED procedure was 35 months (range 14 days to 218 months). Indication for TED was severe persistent reflux in, respectively, 9 cases of EA (7 with coloplasty and 2 with preservation of the native esophagus after atresia repair, associated in 1 case with an esotracheal cleft), 2 cases of esotracheal cleft type III, and 2 cases of esophagocoloplasty for caustic burns. Six patients had undergone previous fundoplications (1-4 procedures) that failed, whereas the remaining patients underwent TED as the primary antireflux procedure. The average follow-up was 26 months (range 1 month to 4 years). There were no complication during the immediate postoperative course. Three children died at 3, 4, and 12 months after the procedure from acute respiratory failure. Respiratory status was improved in 8 children, and recurrent bronchitis was noted in 1 child. Regarding the digestive status, gastrostomy was closed at 18 and 24 months in 2 children, and partial nocturnal enteral nutrition (200 to 900 mL/d) through the gastrostomy remains necessary in the other children. CONCLUSION: Total esophagogastric dissociation procedure improves the respiratory consequences of severe GER, particularly in children for whom other surgical treatments have failed. The long-term safety of this operation remains to be determined especially regarding the consequences of a gastrointestinal Roux-en-Y loop procedure.

Bacterial contamination of enteral nutrition in a paediatric hospital.

A prospective study was performed in a paediatric hospital to evaluate the incidence of bacterial contamination in enteral nutrition bags and to determine the critical points of process. During two separate one-month periods, all children receiving pump-assisted enteral nutrition were enrolled in the study. Samples for microbiological analysis were collected from enteral nutrition bags after administration in the first and second study period (sample T(2)). In the second study period, two additional samples were made at the end of the feed preparation process. One was refrigerated immediately (sample T(0)) and the other was sealed in a tube that followed the enteral nutrition solution until the end of its administration (sample T(1)). Bacterial contamination was detectable above 10(2)cfu/mL. Twenty-six out of 40 patients were included in the first study period and 14 out of 44 in the second study period. Contamination (>10(2)cfu/mL) occurred in nine of 26 samples (35%) and seven of 14 samples (50%) in the first and second study periods, respectively. Of these, five (20%) and three (21%) contained significant contamination (>/=10(4)cfu/mL). Bacteria of low pathogenicity were found in T(0) samples. Bacteria present in T(2) samples were pathogenic and multiple in 50% of cases. These results suggest that manipulation of the enteral nutrition bags at the bedside is critical for bacterial safety.

[Low bone mineral density in children with Crohn's disease]. / Déminéralisation osseuse au cours de la maladie de Chron de l'enfant.

UNLABELLED: Recent studies have reported low bone mineral density in children with Crohn's disease. The aims of this retrospective study were to quantify its frequency and to search for risk factors. POPULATION AND METHODS: Bone mineral density of 29 children with Crohn's disease was measured by dual-energy X-ray absorptiometry. All the children were taking calcium and vitamin D, during all the follow-up. RESULTS: Osteoporosis (Z-score < or = -2.5 S.D.) was found in 38% of the children, and osteopenia in 38% (Z-score between -1 and -2.5 S.D.). Low bone mineral density was correlated with age, suggesting it begins with puberty. Daily corticosteroid exposure was significantly higher for patients with osteoporosis. Disease severity measured with Harvey-Bradshaw index and exposure to immunosuppressive drugs were almost statistically significant. Sex, height, duration and site of disease, nutritional assistance exposure were not associated with low bone mineral density. CONCLUSION: This study confirms the high frequency of low bone mineral density in children with Crohn's disease, mainly during puberty. Corticosteroid exposure is a risk factor, and the disease severity, a probable one (non significant). New treatment strategy has to be defined to prevent and to treat this complication.

Cytokines, chemokine receptors, and homing molecule distribution in the rectum and stomach of pediatric patients with ulcerative colitis.

BACKGROUND: Cytokines appear to play a significant role in the pathogenesis of inflammatory bowel disease (IBD) with a predominant Th2 pattern in colonic mucosa of patients with ulcerative colitis (UC). Chemokines and their receptors also regulate the migration of Th1 or Th2 lymphocytes to inflammatory tissues during the immune response. Although adult UC is usually confined to the colon, pediatric UC not uncommonly affects the stomach. AIMS: The aim of this study was to compare expression of cytokines, chemokine receptors, and homing molecules in the rectal and the histologically characterized gastric mucosa of pediatric patients with UC. SUBJECTS Sixteen patients (11 girls and 5 boys; median age, 9 years) having all the features of UC were included in the study. METHODS: Rectal and gastric mucosa obtained from UC cases were immunostained with antibodies against L-selectin, beta 7 integrin, CXCR3, CCR3, and CCR5. IL-4 and IL-12 p40 transcript expression was studied by in situ hybridization. RESULTS: Chronic gastritis was found in 93.7% of cases and Helicobacter pylori (Hp) was found in 2 (13.3%) cases. In the rectal and gastric mucosa, CXCR3 was found in perivascular lymphocytes and CCR5 in a subset of CXCR3+ cells in the lamina propria. CCR3+ lymphocytes and IL-4-positive cells were always found, but there was no evidence of IL-12 production. Most of the lymphocytes infiltrating the gastric mucosa expressed beta 7 but not CD62L. In contrast, beta 7-positive cells were randomly dispersed in the rectal lamina propria, and the fraction of CD3+beta 7+ was low. CONCLUSIONS: The authors conclude that gastritis is common in pediatric UC. The presence of CCR3+ lymphocytes, IL-4 transcript expression, without IL-12 p40 production in the stomach and in the rectum suggests a Th2 immune response. The presence of CCR3+, CD62L- activated Th2 cells may suggest that these gastric cells are recruited from colorectal primary lesions.

[Failure to thrive and intestinal diseases in congenital disorders of glycosylation]. / Hypotrophie et manifestations digestives des désordres congénitaux de la glycosylation.

UNLABELLED: Congenital disorders of glycosylation type I (GDG-I) is a class of genetic multisystem disorders characterised by defective glycosylation of glycoproteins. The characteristics and mechanisms of failure to thrive and intestinal diseases present in CDG-I are anectodal. PATIENTS AND METHODS: The aim of this study was to analyse 7 CDG-I (4 CDG-Ia, 2 CDG-Ib and 1 CDG-Ix) with important digestive symptoms and failure to thrive in order to characterise the mechanisms implied. RESULTS: Four children had no skin abnormality or dysmorphia (1 CDG-Ia, 2 CDG-Ib, 1 CDG-Ix). An encephalopathy with cerebellar hypoplasia was present only in the 4 CDG-Ia. Failure to thrive and diarrhea were present during the first month of life in 6 and appeared at 5 years in one CDG-Ia associated to mild or severe hepatopathy in all patients. One CDG-Ia, 1 CDG-Ib, 1 CDG-Ix had an exsudative enteropathy. A positive steatorrhea was present in 3 patients. Five patients had an abnormal small bowel biopsy. Abnormalities were variable: moderate inflammation of the chorion without villous atrophy in 2, intra-enterocyte fat accumulation without villous atrophy in 2, and partial villous atrophy with lymphangectasia in 1. In 2 CDG-Ia the intestinal biopsy was normal. Enteral nutrition in 4 and parenteral nutrition in 2 were effective in 4 patients and 1 patient with an exsudative enteropathy respond to a free fat diet (CDG-Ix). CONCLUSION: The digestive symptoms with failure to thrive is a common feature of CDG-I and could be the first symptoms. The diagnostic should be suspected if no other cause is found. Mechanisms of the intestinal symptoms appear to be multiple such as inflammation, abnormal enterocyte lipid transport or intestinal permeability related to the abnormal glycosylation of intestinal mucosa glycoproteins.

Card15 gene overexpression in mononuclear and epithelial cells of the inflamed Crohn's disease colon.

BACKGROUND: Crohn's disease is one of the principal human chronic inflammatory bowel diseases. Although its aetiology is still unknown, its complex pathogenesis has environmental, immunological, and genetic determinants. CARD15 is the first susceptibility gene implicated in the predisposition to Crohn's disease and is known to be expressed only in monocytes. However, its expression in situ has not yet been studied. AIMS: To analyse the tissue distribution of CARD15 and identify cells producing CARD15 in samples of colon from patients with Crohn's disease and control subjects. PATIENTS AND METHODS: We analysed CARD15 gene expression in surgical specimens of colon from eight children with Crohn's disease and nine controls by immunohistochemistry, in situ hybridisation, and reverse transcription-polymerase chain reaction (RT-PCR). RESULTS: We showed that CARD15 was present only in the cytoplasm of macrophages in the normal colon. Increased CARD15 expression was detected in Crohn's disease lesions. There were more CARD15 positive cells in Crohn's disease lesions than in uninvolved areas. Both intestinal epithelial cells, macrophages, and their derivatives overproduced CARD15 in Crohn's disease. To further assess CARD15 expression by intestinal epithelial cells, we performed RT-PCR on freshly isolated intestinal epithelial cells, and showed that these cells isolated from Crohn's disease samples contained more CARD15 mRNA than intestinal epithelial cells from controls. CONCLUSIONS: We have demonstrated that colonic involvement in active Crohn's disease is associated with increased CARD15 gene expression in both macrophages and intestinal epithelial cells. Therefore, this deregulation can affect the host-environment interaction and thus contribute to the pathogenesis of this disease.