Malignancy and mortality in paediatric-onset inflammatory bowel disease: a 3-year prospective, multinational study from the paediatric IBD Porto group of ESPGHAN.

BACKGROUND: Risk benefit strategies in managing inflammatory bowel diseases (IBD) are dependent upon understanding the risks of uncontrolled inflammation vs those of treatments. Malignancy and mortality in IBD have been associated with disease-related inflammation and immune suppression, but data are limited due to their rare occurrence. AIM: To identify and describe the most common causes of mortality, types of cancer and previous or current therapy among children and young adults with paediatric-onset IBD. METHODS: Information on paediatric-onset IBD patients diagnosed with malignancy or mortality was prospectively collected via a survey in 25 countries over a 42-month period. Patients were included if death or malignancy occurred after IBD diagnosis but before the age of 26 years. RESULTS: In total, 60 patients were identified including 43 malignancies and 26 fatal cases (9 due to cancer). Main causes of fatality were malignancies (n = 9), IBD or IBD-therapy related nonmalignant causes (n = 10; including 5 infections), and suicides (n = 3). Three cases, all fatal, of hepatosplenic T-cell lymphoma were identified, all were biologic-naïve but thiopurine-exposed. No other haematological malignancies were fatal. The 6 other fatal cancer cases included 3 colorectal adenocarcinomas and 3 cholangiocarcinomas (CCAs). Primary sclerosing cholangitis (PSC) was present in 5 (56%) fatal cancers (1 colorectal carcinoma, 3 CCAs and 1 hepatosplenic T-cell lymphoma). CONCLUSIONS: We report the largest number of paediatric-onset IBD patients with cancer and/or fatal outcomes to date. Malignancies followed by infections were the major causes of mortality. We identified PSC as a significant risk factor for cancer-associated mortality. Disease-related adenocarcinomas were a commoner cause of death than lymphomas.

The humoral immune response to Helicobacter pylori infection in children with recurrent abdominal pain.

The systemic humoral immune response to Helicobacter pylori antigens was investigated in 36 children with recurrent abdominal pain (RAP). H. pylori was cultured and Helicobacter-like organisms (HLO) were seen in six children, three of whom had active and two inactive chronic gastritis. None of these children had endoscopic abnormalities. All sex children had increased IgG antibodies to heat-stable H. pylori antigens which were of the IgG1 and IgG3 subclasses. Using six other IgG tests, four of which were commercially available, two to five H. pylori-positive children were found seropositive. Five of six H. pylori-negative children with inactive chronic gastritis and no endoscopic abnormalities had increased IgM antibody levels in addition to increased or borderline increased IgG antibody levels to H. pylori, indicating activity in a chronic H. pylori infection. Five children without H. pylori and with no morphological changes, but with gastritis or duodenitis by endoscopy, had significantly lower IgG and IgA antibody levels compared to other groups. Six of nineteen children without H. pylori, and with no morphological or endoscopic changes had increased IgG and IgM antibody levels to H. pylori. All H. pylori-negative children were seronegative by the four commercial kits. Overall, 12 (33%) of 36 children with RAP were either H. pylori positive by culture and microscopy or had increased IgG antibody levels to H. pylori, which is significantly different from the 10-14% seropositive rate of asymptomatic children. H. pylori may therefore be a cause of RAP in one quarter to one third of the children with RAP in whom other etiologies of RAP are excluded. Further studies on a large number of children are needed for an extended evaluation of the humoral immune response to H. pylori and for further examination of commercial kits which seem to give a high number of false-negative results.

[Gallstones in children]. / Galdesten hos børn.

Children of all ages, including neonates, can have gallstones. According to international data the incidence seems to be increasing, but Danish data are missing. The most frequent associated conditions are haemolytic anaemia, children treated with total parenteral nutrition, and children who have undergone abdominal surgery, while older children with pregnancy or obesity are disposed. Between 40 and 65% have cholelithiasis on an idiopathic basis. When spontaneous dissolution of the gallstones is not to be expected, the treatment is surgery, and laparoscopic cholecystectomy is a well-described, safe and mini-invasive treatment, which can also be recommended for children.

[Pediatric colonoscopy]. / Paediatrisk koloskopi.

The procedure and results of 50 colonoscopies performed over a three-year period on a group of 43 children (range: 0.3-16 yr; median: 9 yr) are described. The main indications were evaluation for, or control of already known, chronic inflammatory bowel disease (n = 38) and rectal bleeding (n = 8). Following verbal and written information the children were admitted one to two days before the procedure for bowel preparation. Children < 10 years old received general anaesthesia during the colonoscopy (n = 25) and most children > or = 10 years old received an intravenous sedation with pethidine and midazolam (n = 25). In only one case was intravenous sedation not successful. The coecum was visualised in 96% and the terminal ileum intubated in 77% (when intended) of the endoscopies. The most important results obtained were establishment of the diagnosis of inflammatory bowel disease in 21 of 30 suspected cases and the removal of a polyp in two cases. At the time of colonoscopy a "best guess" diagnosis of either ulcerative colitis or Crohn's disease often predicted the histological diagnosis, but endoscopy tended to underestimate the severity and extent of the inflammation as compared to microscopy. There were no complications. We conclude that colonoscopy performed according to our recommendations is a safe and informative procedure for evaluation of the large bowel and terminal ileum in children with intestinal disease.

[Esophago-gastro-duodenoscopy of pediatric patients]. / Osofago-gastro-duodenoskopi af paediatriske patienter.

In total 199 oesophago-gastro-duodenoscopies (OGD) were performed in 71 female and 71 male paediatric patients (three months-15 years, median 8 years 2 months). The endoscopy was performed in general anaesthesia in children less than five years old, and in an intravenous sedation in older patients. The indications for OGD were: recurrent abdominal pain and concomitant positive antibodies against Helicobacter pylori as a part of a scientific project, upper dyspepsia, upper gastrointestinal bleeding, failure to thrive, coeliac disease, suspicion of chronic inflammatory bowel disease and a percutaneous gastrostomy. Seventy-two OGD were carried out in general anaesthesia, 86 in intravenous sedation with midazolam and pethidine and 41 in intravenous midazolam sedation. Complications related to the sedation or to the endoscopy were not observed. Amnesia was reported in 94/95 children who were sedated intravenously with midazolam and pethidine or midazolam alone. Six endoscopies could not be carried out in intravenous sedation because of agitation. In the primary OGD endoscopy revealed a normal mucosa in 121/142 (85%), oesophagitis in four (3%), nodular mucosa in six (4%), gastritis in four (3%) and a duodenal ulcer in one (0.7%). Histology disclosed active or inactive chronic gastritis at the primary endoscopy in 35/69 (51%) of the children with recurrent abdominal pain and antibodies against H. pylori. In children with failure to thrive an avillous duodenal mucosa was seen in 3/32 (9%). A comparison between histological and stereomicroscopical evaluation of the duodenal biopsies revealed agreement in 41/47 (87%). We conclude that OGD is a safe and tolerable procedure in paediatric patients, in whom possible morphological changes are suspected. The indications for an OGD need further evaluation.