Outcome after restorative proctocolectomy and ileal pouch-anal anastomosis in children and adults.

BACKGROUND: Studies comparing the outcome of ileal pouch-anal anastomosis (IPAA) in children and adults are scarce. This complicates decision-making in young patients. The aim of this study was to compare adverse events and pouch function between children and adults who underwent IPAA. METHODS: This cross-sectional cohort study included all consecutive children (aged less than 18 years) and adults with a diagnosis of inflammatory bowel disease or familial adenomatous polyposis who underwent IPAA in a tertiary referral centre between 2000 and 2015. Adverse events were assessed by chart review, and pouch function by interview using a pouch function score (PFS). RESULTS: In total, 445 patients underwent IPAA: 41 children (median age 15 years) and 404 adults (median age 39 years), with a median follow-up of 22 (i.q.r. 8-68) months. Being overweight (P = 0·001), previous abdominal surgery (P = 0·018), open procedures (P < 0·001) and defunctioning ileostomy (P = 0·014) were less common among children than adult patients. The occurrence of anastomotic leakage, surgical fistulas, chronic pouchitis and Crohn's of the pouch was not associated with paediatric age at surgery, nor was pouch failure. The development of anastomotic strictures was associated with having IPAA surgery during childhood (odds ratio 4·22, 95 per cent c.i. 1·13 to 15·77; P = 0·032). Pouch function at last follow-up was similar in the children and adult groups (median PFS 5·0 versus 6·0 respectively; P = 0·194). CONCLUSION: Long-term pouch failure rates and pouch function were similar in children and adults. There is no need for a more cautious attitude to use of IPAA in children based on concerns about poor outcome.

Raised faecal calprotectin is associated with subsequent symptomatic relapse, in children and adolescents with inflammatory bowel disease in clinical remission.

BACKGROUND: Reliable data on inflammatory biomarkers for predicting relapse of paediatric inflammatory bowel disease (IBD) are lacking. AIM: To investigate the predictive value of faecal calprotectin (FC) and CRP for symptomatic relapse in pediatric IBD in clinical remission. METHODS: In this cross-sectional cohort study, patients <18 years with Crohn's disease or ulcerative colitis in clinical remission ≥3 months were included. At baseline, clinical and biochemical disease activity were assessed using the abbreviated-Pediatric Crohn's Disease Activity Index or Pediatric Ulcerative Colitis Activity Index, and FC and CRP respectively. Disease course over the subsequent 12 months was retrospectively assessed. RESULTS: In total, 114 patients (56% males; median age 14.9 years) were included. Baseline FC was higher in patients that developed symptomatic relapse [median (IQR), relapse 370 µg/g (86-1100) vs. remission 122 µg/g (40-344), P = 0.003]. Baseline FC was predictive of symptomatic relapse within 6 months [HR per 250 µg/g (95% CI): 1.46 (1.21-1.77), P < 0.001], with good predictive accuracy (AUC: 0.82). Optimal FC cut-off was 350 µg/g, with positive and negative predictive value of 41% and 96%. Baseline CRP was higher in patients that developed symptomatic relapse [median (IQR), relapse 1.0 µg/g (0.6-5.0) vs. remission 1.0 µg/g (0.4-2.0), P = 0.033]. Baseline CRP was predictive of symptomatic relapse within 6 months from baseline [HR per 1 mg/L (95% CI): 1.10 (1.02-1.19), P = 0.011], with fair predictive accuracy (AUC: 0.72). Optimal CRP cut-off was 1.0 mg/L, with positive and negative predictive value of 21% and 94%. CONCLUSIONS: Faecal calprotectin and CRP are predictive of symptomatic relapse and may be valuable in management of paediatric IBD in clinical remission.

The prevalence of irritable bowel syndrome-type symptoms in paediatric inflammatory bowel disease, and the relationship with biochemical markers of disease activity.

BACKGROUND: A large proportion (25-46%) of adults with inflammatory bowel disease in remission has symptoms of irritable bowel syndrome (IBS), which are thought to reflect ongoing inflammation. Data on paediatric inflammatory bowel disease patients are lacking. AIM: To investigate (i) the prevalence of IBS-type symptoms in paediatric inflammatory bowel disease patients in remission and (ii) the relationship of IBS-type symptoms with biochemical markers of disease activity. METHODS: This cross-sectional study included all patients (<18 years) with Crohn's disease or ulcerative colitis attending the out-patient clinic of one of three Dutch hospitals between March 2014 and June 2015. Clinical disease activity was determined using the abbreviated-PCDAI or PUCAI. Biochemical disease activity was assessed using faecal calprotectin and serum CRP. IBS-symptoms were assessed using physician-administered Rome III-questionnaires. RESULTS: We included 184 patients (92 female; mean age: 14.5 years) (Crohn's disease: 123, ulcerative colitis: 61). The prevalence of IBS-type symptoms in children with inflammatory bowel disease in clinical remission was 6.4% (95% CI: 2.5-11.1%; Crohn's disease: 4.5%; ulcerative colitis: 10.8%). Prevalence of IBS-type symptoms in children with faecal calprotectin <250 µg/g was 16.1% (95% CI: 7.6-25.8%; Crohn's disease: 16.7%; ulcerative colitis: 10.8%). No difference in faecal calprotectin or CRP was found between patients in clinical remission with or without IBS-type symptoms (faecal calprotectin: IBS+ median 58 µg/g, IBS- 221 µg/g, P = 0.12; CRP: IBS+ median 1.4 mg/L, IBS- 1.1 mg/L, P = 0.63). CONCLUSIONS: The prevalence of IBS-type symptoms in children with inflammatory bowel disease is highly dependent on the definition of remission. Nonetheless, the prevalence is much lower than that previously reported in studies in adult inflammatory bowel disease patients. IBS-type symptoms appear to be unrelated to gastrointestinal inflammation.

The duration of effect of infliximab maintenance treatment in paediatric Crohn's disease is limited.

BACKGROUND: Infliximab is effective for induction and maintenance of remission in children with moderately to severely active Crohn's disease (CD). AIM: To evaluate the long-term efficacy of infliximab treatment in paediatric CD. METHODS: In this observational, multicentre study, all paediatric CD patients in The Netherlands treated with infliximab from October 1992 to November 2009 and with minimal follow-up of 3 months since start of infliximab, were studied. RESULTS: One hundred and fifty-two CD patients [81M; median age at start of infliximab 15.0 years (IQR 13.1-16.4)] received a median number of 10.5 infliximab infusions (IQR 6-21). Median follow-up after start of infliximab was 25 months (IQR 13-40). Kaplan-Meier analysis showed that the cumulative probability of losing response to infliximab in patients who initially required repeated infusions was 13%, 40% and 50% after 1, 3 and 5 years, respectively. Seventy-four patients (49%) needed dose adjustments, with a median time to any adjustment of 6 months. CONCLUSIONS: Duration of effect of infliximab is limited as 50% of patients on infliximab maintenance treatment lose their therapeutic response after 5 years. Dose adjustments after start of infliximab are frequently needed to regain therapeutic benefit. These findings emphasise the need for effective, long-term treatment strategies for paediatric CD.

[Diagnostic methods for Helicobacter pylori infection in children]. / Diagnostiek naar Helicobacter pylori-infectie bij kinderen.

A Helicobacter pylori infection is usually acquired during early childhood. Poor socioeconomic circumstances form an important risk factor for this. An untreated infection may lead to peptic ulceration and, particularly in adults, to gastric cancer and mucosa associated lymphoid tissue (MALT) lymphoma. The gold standard for the diagnosis of H. pylori infection is gastroscopy with histology and culture of biopsy specimens. Non-invasive tests are serology, 13C-urea breath test and stool antigen test. The sensitivity and specificity of serology tests are low in children, but for both the 13C-urea breath test and the stool antigen test the sensitivity and specificity are high. A 'test and treat' approach is advised with due consideration for possible symptoms and the risk for peptic ulcers and gastric cancer at a more advanced age. The treatment results must be evaluated. If necessary, young children can be treated at a later age.

Evaluation of two commercial enzyme immunoassays, testing immunoglobulin G (IgG) and IgA responses, for diagnosis of Helicobacter pylori infection in children.

Serological testing to diagnose Helicobacter pylori infection in children is still controversial, although commonly used in clinical practice. We compared the immunoglobulin G (IgG) and IgA results of two commercially available enzyme immunoassays (EIAs) (Pyloriset IgG and IgA and Enzygnost II IgG and IgA) for 175 children with abdominal symptoms divided into three age groups (0 to < or =6 years, n = 47; >6 to < or =12 years, n = 77; >12 years, n = 51). A child was considered H. pylori infected if at least two of three tests (histology, rapid urease test, 13C-urea breath test) or culture were positive and noninfected if all results were concordantly negative. Of 175 children, 93 (53%) were H. pylori negative and 82 were H. pylori positive. With the recommended cutoff values, the overall specificity was excellent for all four EIAs (95.7 to 97.8%) regardless of age. Sensitivity varied markedly between tests and was 92.7, 70.7, 47.5, and 24.4% for Enzygnost II IgG, Pyloriset IgG, Enzygnost II IgA, and Pyloriset IgA, respectively. Sensitivity was low in the youngest age group (25 to 33.3%), except for Enzygnost II IgG (91.6%). Receiver-operating curve analyses revealed that lower cutoff values would improve the accuracy of all of the tests except Enzygnost II IgG. Measurement of specific IgA, in addition to IgG, antibodies hardly improved the sensitivity. The specificity of commercial serological tests is high in children when the cutoff values obtained from adults are used. In contrast, sensitivity is variable, with a strong age dependence in some, but not all, tests. We speculate that young children may have a different immune response to H. pylori, with preferable responses to certain antigens, as well as lower titers than adults. The Pyloriset test may fail to recognize these specific antibodies.

Evaluation of a rapid whole blood test to detect Helicobacter pylori infection in children.

BACKGROUND: Rapid, patient near tests for detecting antibodies against Helicobacter pylori are offered for clinical use. We evaluated the BM-Test (Boehringer Mannheim, Germany; identical to the Helisal Rapid Blood Test) in children with recurrent abdominal pain. METHODS: The BM-Test and 13C-urea breath test (UBT) were performed in 195 children (4-18 years). Symptoms were assessed using a 4-week diary. Upper endoscopy was performed in all UBT-positive children and in UBT-negative children with symptoms suggestive of organic disease. H. pylori status was considered positive if at least two of three methods (UBT, histology or rapid urease test) or culture were positive. RESULTS: After exclusion of children with previous H. pylori therapy (n = 8) and undetermined H. pylori status (n = 1), 61/186 (33%) children were H. pylori positive. The BM-Test in relation to H. pylori status revealed a sensitivity of 54%, specificity of 90%, a likelihood ratio of 5.2 for a positive, and of 0.4 for a negative test result. Accuracy of the test was independent of ethnicity, gender, age, family history for ulcer disease, frequency or severity of abdominal symptoms, epigastric tenderness, type of blood sampling (capillary versus venous) and DOB values of the UBT. In eight previously treated children, the test gave one false-positive and three false-negative results. CONCLUSIONS: Almost half of H. pylori-infected children and 10% of non-infected children were misclassified by the BM-Test. False-negative results are not related to young age or certain ethnic groups. The poor performance makes the test unsuitable for epidemiological and clinical use in children.

Influence of age on 13C-urea breath test results in children.

BACKGROUND: The 13C-urea breath test for diagnosis of Helicobacter pylori infection has not been validated in infants and young children. The influence of age on the test results was studied by conventional validation against invasive methods and by mathematical estimation in a large pediatric population. METHODS: The breath test was performed in 1499 children aged 2 months to 18 years. After a fasting period of 4 hours or more, 75 mg 13C-urea was ingested with cold apple juice, breath samples were taken at baseline and at 15 and 30 minutes. The distribution of the natural logarithms of the delta-over baseline (DOB) values were calculated, and the optimal cutoff values between positive and negative test results and gray zones with a risk of misclassification more than 10% were determined for both time points. In a subgroup of 149 children results of the breath test were compared with concordant results of histology and rapid urease test; 53 of them were less than 6 years of age. RESULTS: Logarithmic results of 1499 breath tests revealed two normally distributed subgroups with minimal overlap. The calculated optimal cutoff values were 4.7/1000 at 15 minutes and 5.0/1000 at 30 minutes. At 30 minutes, only 2.6% of all results were in the calculated gray zone (2.6-6.5/1000). Age was negatively correlated to DOB values of both negative (r = -0.223) and positive results (r = -0.291; P < 0.001). Breath test-negative and -positive children 6 or less years of age had significantly higher mean DOB values (P < 0.02) and a larger proportion of results within the gray zone than older children. Compared with biopsy-based results, the least discrepancies occurred at a cutoff of 5.0/1000: 0 of 61 infected (sensitivity 100%) and 6 of 88 noninfected children. Because five of the false-positive results were obtained in children less than 6 years of age, specificity and positive predictive values were lower in this age group than in older patients (88.1% vs. 97.8% and 68.8% vs. 98.0%, respectively). CONCLUSIONS: Under the applied conditions, the 13C-urea breath test shows an excellent separation between positive and negative results. Because of some overlap and a strong age effect, definition of a gray zone appears more meaningful than a threshold value. Because infants and young children have a high risk for false-positive breath test results, the values for cutoff and gray zones may have to be adapted. Further validation studies against invasive methods are warranted in this age group.

Why do patients seek treatment in hospitals of complementary medicine?

OBJECTIVE: This exploratory study evaluated patients' reasons for entering a complementary (alternative) medicine hospital by ranking 15 medical and psychosocial factors that were thought to influence this choice. SUBJECTS AND OUTCOME MEASURES: Two hundred patients (200) from two complementary hospitals, one focusing on Traditional Chinese Medicine and one on the Western type of complementary medicine, completed an extensive questionnaire at the beginning of their inpatient treatment. The questionnaire covered personal background; disease parameters; attitude towards conventional medicine; previous experience with, and knowledge of, complementary therapies; expectations concerning the forthcoming treatment; health-related habits; personality traits; and social support. RESULTS: Optimistic attitudes towards treatment and a positive appraisal of alternative doctors were frequently stated reasons (80%), as was the disease severity (long duration: 86%; acute progression or imminent surgery: 70%). Previous successes with complementary therapies, however, ranked relatively low (53%). Negative opinions concerning conventional therapies and conventional doctors' treatments were mentioned by 68% of the patients. Many patients felt themselves to be under considerable psychologic stress (74%). A majority (73%) was well informed about complementary therapies, and 65% were curious about the forthcoming therapies. Sixty-eight percent (68%) indicated good health behaviors. Fewer patients mentioned contemplative and/or religious attitudes (44%) or lack of social support (25%). Age primarily accounted for variations in the ranking weights of the two subgroups. The specific type of complementary medicine was of minor influence. In 14 out of 21 personality dimensions, the current patient group showed significant deviations from the healthy reference, which is in good agreement with findings from conventionally treated patients.

[Protein-losing giant fold gastritis in childhood--a case report and differentiation from Ménétrier disease of adulthood]. / Eiweissverlierende Riesenfaltengastritis im Kindesalter--ein Fallbericht und Abgrenzung zum Morbus Ménétrier des Erwachsenenalters.

We report on a 2.5-year-old boy, who presented with vomiting since one week and periorbital and pitting edema. Laboratory studies revealed hypoproteinemia and hypoalbuminemia without signs of renal or liver disease. The cause of protein loss was giant fold gastritis disclosed by upper endoscopy. Biopsies revealed foveolar hyperplasia with cystic dilatation of the glands, identical to Ménétrier's disease in adulthood. About 55 cases of hypertrophic gastropathy in children have been published. In contrast to the chronic course of Ménétrier's disease in adults, the pediatric cases are generally benign, self-limited with complete resolution typically within a few weeks. While the etiology of Ménétrier's disease is still unknown, the benign pediatric hypertrophic gastropathies have been associated with infections, primarily CMV and occasionally helicobacter pylori, herpes simplex and mycoplasma. Supportive treatment with a high-protein-diet and intravenous albumin transfusions is recommended. H2-receptor antagonists might improve symptoms.

The use of stable isotope techniques for nutritional and metabolic research in paediatrics.

Stable isotope methods are increasingly used in paediatrics for clinical diagnosis and research due to marked improvements in analytical technologies and better availability of suitable tracers. The safety of stable isotopes is of major importance for use in children. Large amounts of deuterium well above the doses applied under clinical conditions may induce adverse effects. In contrast, heavier stable isotopes such as 13C, 15N or 18O do not induce adverse effects even at the highest enrichments obtained, and they are safe. Breath tests with measurements of 13CO2 enrichment after oral application of a tracer can reliably evaluate helicobacter pylori infection and gastric emptying kinetics. Combined with an estimation of total CO2 production, 13CO2 breath tests allow estimation of the absorption and oxidation of 13C-labelled substrates, such as medium- and long-chain triglycerides, and demonstrates the beneficial effect of carnitine supplements on fat oxidation in primary carnitine deficiency. The study of metabolic processes may require the sampling of blood for isotopic analyses of metabolites of the applied tracer. Gas chromatography-isotope ratio mass spectrometry can detect tracer in individual components from small plasma samples. The high precision enabled us to utilize the small differences in natural 13C-enrichment between dietary fats to study fatty acid turnover in term infants, in whom the dietary fat source was switched to corn oil with a slightly higher 13C-content. With this approach we demonstrated active conversion of linoleic into arachidonic acid. We also applied biotechnologically produced, U-13C labelled linoleic and alpha-linolenic acids to infants and detected the conversion of these essential fatty acids to their longer chain polyunsaturated derivatives, with an apparent change of conversion activity with age. Moreover, it has become possible to measure tissue protein synthesis from small biopsy samples obtained in situ without surgery, such as forceps biopsies of rectal tumors. These few examples of recent developments demonstrate the great clinical and scientific potential of stable isotope methods in future paediatric applications.

[Comparison of perforated metal ceiling systems (supported airflow ceilings) with laminar airflow ceilings in type A (DIN 1946 T.4) operating rooms under surgical conditions]. / Vergleich von Lochblechdeckensystemen (Stützstrahldecken) mit Gewebedeckensystemen in OP-Räumen des Typs A (DIN 1946 T.4) unter Operationsbedingungen.

In eleven centrally ventilated operating theatres the concentration of particles and airborne germs in wound vicinity was measured on three workdays. Five theatres were equipped with air supply ceilings with supporting flow outlets (supporting flow ceilings), five with laminar air flow ceilings and one with an air supply ceiling, a body exhaust system and a partition wall between the anesthetic and operating areas. Under routine conditions the air supply of the laminar air flow ceiling with its lower turbulence shielded the operating field from the largely staff-related air contamination in the rest of the theatre better than in the case of the supporting flow ceilings. Particles and airborne germs were removed from the endangered wound area faster. A spatial separation between the anesthetic and the operating areas as well as a body exhaust system lead to a considerable reduction of the contamination. Two theatres were conspicuous by reason of their considerably raised values due to defective control engineering and the wrongly positioning of the operating table. From the point of view of ventilation technique the laminar air flow ceilings with lower turbulence are superior to air supply ceilings with supporting flow outlets in the working day of an operating theatre. In order to minimize the influence of the staff, which up till now has been neglected in testing specifications, constructional possibilities such as the size of ceiling, the partitioning off of operating and anaesthetic areas and the positioning of the operating table in relation to the incoming air should be coordinated rationally. Taking measurements regularly during operations can provide the impulse for considerable improvements in both operational and planning phases.