Jarosław Walkowiak

Defining DIOS and Constipation in Cystic Fibrosis With a Multicentre Study on the Incidence, Characteristics, and Treatment of DIOS

Objectives: Various definitions for distal intestinal obstruction syndrome (DIOS), meconium ileus equivalent, and constipation in patients with cystic fibrosis (CF) are used. However, an unequivocal definition for DIOS, meconium ileus equivalent, and constipation is preferred. The aims of this study were, therefore, to seek consensus on the definitions for DIOS and constipation in patients with CF and to determine the incidence, characteristics, and treatment of DIOS in a cohort of paediatric patients with CF. Methods: During the 2005 European Society for Paediatric Gastroenterology, Hepatology, and Nutrition meeting in Porto a group of paediatric gastroenterologists discussed the definition of DIOS and constipation in CF. Subsequently, all patients younger than or equal to 18 years with complete DIOS according to the definition agreed upon and diagnosed during the years 2001 to 2005 in 8 CF centres were studied. Results: Distal intestinal obstruction syndrome was defined as an acute complete or incomplete faecal obstruction in the ileocaecum, whereas constipation was defined as gradual faecal impaction of the total colon. Fifty-one episodes of DIOS in 39 patients were recorded, giving an overall incidence of 6.2 (95% confidence interval, 4.4–7.9) episodes per 1000 patient-years. Of the 39 patients with DIOS, 20% experienced a relapse, 92% were pancreatic insufficient, 44% had a history of meconium ileus at birth, and 82% had a severe genotype. Conservative treatment was effective in 49 of 51 DIOS episodes (96%). Conclusions: The European Society for Paediatric Gastroenterology, Hepatology, and Nutrition CF Working Group definitions of DIOS and constipation in CF are specific and make a clear distinction between these 2 entities. The incidence of DIOS in the present study was considerably higher than reported previously.

Indirect pancreatic function tests in children

Department of Gastroenterology and Metabolism, Poznan University of Medical Sciences, Poznan, Poland; 4th Department of Pediatrics, Aristotle University, Thessaloniki, Greece; Klinik und Poliklinik für Kinderund Jugendmedizin des Universitätsklinikums Dresden, Germany; University Children’s Clinic, Tübingen, Germany; Department of Pediatric Gastroenterology, Erasmus MC-Sophia, Rotterdam, The Netherlands; Department of Child Health, University of Wales Swansea, Singleton Hospital, Swansea, United Kingdom

Secular changes in body height and weight in children and adolescents in Poznan, Poland, between 1880 and 2000

Aim: A secular trend in body height and weight is well documented. The first observations concerning this phenomenon in Poland were made at the end of the 19th century. The aim of this study was to assess changes in body height and weight during the 20th century, with special emphasis on the last decade. Methods: The results of body height and weight measurements obtained in eight subsequent surveys (1880–1886, 1922–1927, 1946–1950, 1960–1961, 1970–1971, 1980–1981, 1990–1991 and 1999–2000) were included in the analysis. Mean values were compared and differences between the surveys were analysed. Results: In general, in the 20th century, children grew taller and heavier and reached final body height and weight more rapidly. The biggest differences in body height and weight in the 20th century, observed at growth spurt, were about 17 cm and 11kg, respectively, for boys, and 13 cm and 13 kg for girls. The magnitude of secular changes in body height and weight in the 20th century was not stable. There were periods of increased and decreased intensity of acceleration of physical development (the 1950s and 1970s, and the 1960s and 1980s, respectively), as well as a period of deceleration (the 1940s). In the last decade, the tendency has been towards deceleration in most age groups studied.

Comparison of Fecal Elastase-1 Determination with the Secretin-Cholecystokinin Test in Patients with Cystic Fibrosis

BACKGROUND The secretin-cholecystokinin (CCK) test is the gold standard in the evaluation of exocrine pancreatic insufficiency. Because of its invasive character, it is of limited value in cystic fibrosis (CF) patients, especially in those with severe respiratory disease. The aim of the study was to evaluate the sensitivity of fecal elastase-1 in relation to the secretin-CCK test and quantitative fecal fat excretion in CF patients. METHODS The study comprised 28 patients (11 females and 17 males) aged 4 to 20 years. In all patients the secretin-CCK test and determination of fecal elastase-1 concentration (with enzyme-linked immunosorbent assay) and fecal fat excretion were performed. RESULTS The range of fecal elastase-1 was from undetectable to 485 microg/g (mean, 84.6+/-119.9 microg/g) and of fecal fat excretion from 1.0 to 55.1 g/day (mean, 15.0+/-12.2 g/day). On the basis of the results of the secretin-CCK test (and fecal fat analysis) exocrine pancreatic insufficiency was divided into three subgroups: mild (I), moderate (II), and severe (III). Four patients were classified in subgroup I, 4 in II and 20 in III. Fecal elastase (elastase-1) results were 332.0+/-124.9 microg/g in subgroup I, 96.9+/-45.7 microg/g in subgroup II, and 32.1+/-41.2 microg/g in subgroup III. The fecal elastase-1 sensitivity with a cut-off point of 200 microg/g was 89.3% for all patients, 100% for patients in subgroups II and III, but only 25.0% for patients in subgroup I; the specificity was 96.4%. Linear regression analysis showed a statistically significant correlation between fecal elastase (elastase-1) and duodenal volume, bicarbonate, amylase, lipase, and trypsin secretion (in all cases P < 0.001). CONCLUSIONS Measurement of fecal elastase-1 is simple and very useful for assessing the exocrine pancreatic function in CF patients. Elastase is highly specific in severe and moderate exocrine pancreatic insufficiency, but it is rather unspecific for milder forms of pancreatic insufficiency.

Early decline of pancreatic function in cystic fibrosis patients with class 1 or 2 CFTR mutations.

Background: Most cystic fibrosis (CF) patients develop steatorrhea and require pancreatic enzyme replacement therapy. However, there are few data regarding the decline of exocrine pancreatic function within the first years of life in relation to CF genotype. We assessed the decline of pancreatic function in CF infants carrying class 1 or 2 CFTR mutations who were diagnosed in a neonatal screening program. Materials and Methods: Twenty-eight CF patients were included in the study and 27 completed the study. In all subjects, fecal pancreatic elastase-1 concentrations and fecal fat excretion were scheduled to be determined at diagnosis, at 6 months of age and subsequently at 6-month intervals. Results: In all CF patients, fecal pancreatic elastase-1 concentrations of the first assay after diagnosis (3 to 4 months of age) were lower than the cut-off level for normals of <200 μg/g stool. Steatorrhea was found in 81.5% of these subjects. At the age of 6 months, all screened CF subjects had fecal pancreatic elastase-1 concentrations <100 μg/g and at the age of 12 months all were pancreatic insufficient. At that time, having proved pancreatic insufficiency in all studied subjects, we stopped the scheduled further assessment. Conclusion: CF patients require careful monitoring of pancreatic status from diagnosis onwards. In patients carrying class 1 or 2 CFTR mutations, pancreatic insufficiency develops in the first months of life. The proper assessment of pancreatic insufficiency and intestinal malabsorption is crucial for the early introduction of pancreatic enzymes.

The changing face of the exocrine pancreas in cystic fibrosis: pancreatic sufficiency, pancreatitis and genotype.

TABLE. No caption available Cystic fibrosis (CF) is the most frequent cause of exocrine pancreatic insufficiency in childhood. The cystic fibrosis transmembrane conductance regulator (CFTR) gene encodes CFTR protein that functions as cyclic AMP-dependent chloride channel allowing the passage of anions and secondarily water into the lumen of pancreatic ducts. Luminal chlorides are exchanged for bicarbonates. The lack of CFTR channel or its disrupted function (being the consequence of CFTR gene mutations) results in reduced volume of more acidic secretion. It has been suggested that such a situation leads to the precipitation of highly concentrated protein-containing secretion with obstruction and organ damage. The intensity of this process determines the progression of the disease. Steatorrhea is the significant symptom of classical form of CF. Residual pancreatic secretion in a subset of patients, however, allows for normal lipid digestion and absorption. Previous cross-sectional clinical studies estimated that about 85–90% of CF patients in preschool, school and older age are pancreatic insufficient. More frequent detection of mild and nonclassic forms of CF leads to higher frequency of pancreatic sufficiency (PS). The potential decline of exocrine pancreatic function, however, should be always considered. All PS patients with at least one severe or unknown CFTR mutation should be longitudinally assessed for the progression of pancreatic dysfunction. Recurrent acute and chronic pancreatitis is not a rare clinical condition in PS patients with PS: it might be the presenting symptom, even preceding CF diagnosis by several years. Potential appearance of this complication in individuals with pancreatic insufficiency demands elucidation.

Longitudinal follow-up of exocrine pancreatic function in pancreatic sufficient cystic fibrosis patients using the fecal elastase-1 test.

BackgroundA progressive decline in pancreatic function is possible in cystic fibrosis (CF) patients with exocrine pancreatic sufficiency. The secretin–cholecystokinin test is invasive and not acceptable as a repeatable procedure for children. Steatorrhea, conversely, has low sensitivity. Therefore, the aim of the present study was to evaluate the usefulness of the noninvasive fecal elastase-1 (E1) test for the longitudinal assessment of exocrine pancreatic function (EPF) in pancreatic-sufficient (PS) CF patients. MethodsOne hundred eighty-four CF patients were included in the study. In all subjects, E1 concentrations and fecal fat excretion were measured. PS patients were followed for 5 years. ResultsAt the beginning of the study, 35 (19.0%) CF patients were PS, and 32 (17.4%) had normal E1 concentrations. Longitudinal measurements of E1 concentrations in PS patients with CF demonstrated stable enzyme output in 27 and gradual decrease in 8. The decrease was rapid in five infant patients and gradual in three older patients. The decrease of E1 concentrations preceded the appearance of steatorrhea in all eight subjects. ConclusionsThe decline of EPF in patients with CF appears more frequently during the first months and years of life. However, late PS to pancreatic-insufficient (PI) conversion is also possible. The appearance of maldigestion is preceded by the decrease of fecal E1 concentration. Thus, the fecal E1 test is a helpful screening tool for the longitudinal assessment of declining EPF in PS patients with CF to demonstrate pancreatic deterioration. In suspected patients, fecal fat excretion should be assessed.

Fecal pyruvate kinase: a potential new marker for intestinal inflammation in children with inflammatory bowel disease.

Objective. Inflammatory bowel disease (IBD) in children creates diagnostic and clinical challenges. Clinical data, endoscopic appearance and the histopathological assessment of biopsies are essential for diagnosis. However, new methods are required for non-invasive follow-up. Recently, we demonstrated that the dimeric isoform of pyruvate kinase (PK) detected in stool might serve as a potential non-invasive screening tool in inflamed pouch mucosa. The aim of this study was to investigate whether this test could be used to detect intestinal inflammation in pediatric IBD patients. Material and methods. Fecal PK immunoreactivity was assessed in 75 patients with proven ulcerative colitis (UC) and 32 with Crohns disease (CD). Pediatric Crohn Disease Activity Index (PCDAI) and Truelove-Witts scores were determined in CD and UC patients, respectively. Thirty-five healthy subjects (HS) served as a control group. Results. Increased PK levels were documented in 94.1% and 100% active CD patients with a cut-off level of 5 U/g and a cut-off level of 4 U/g, respectively, and in 94.3% of active UC patients regardless of cut-off level. Enzyme immunoreactivity was significantly higher in all IBD patients than in HS. Abnormal PK results were documented in 71.7% of all IBD patients (65.3% and 84.4 for UC and CD patients, respectively). Enzyme levels in UC remission were significantly lower than in the active phase. Enzyme immunoreactivity significantly correlated to both scoring systems. Conclusions. The measurement of stool PK could be a potentially useful marker of IBD activity in children. However, its clinical value demands further studies for comparison with other tests.

Fecal pyruvate kinase (M2-PK): A new predictor for inflammation and severity of pouchitis

A dimeric isoform of pyruvate kinase (TuM2-PK) in stool has been suggested as a useful screening marker for gastrointestinal cancers with 73% sensitivity and 78% specificity [1]. Pyruvate kinase is a ubiquitous enzyme present in virtually all prokaryotic and eukaryotic cells catalyzing the regulatory step in the glycolytic pathway, the conversion of phosphoenolpyruvate (PEP) to pyruvate. Pyruvate kinase exists in two different isotypes: its tetrameric form (M1) has been found in skeletal muscles, heart and brain, whereas the dimeric form (M2) is present in undifferentiated and proliferating tissues [2]. Increased TuM2-PK concentration in polymorphonuclear neutrophils was documented in patients with polytrauma [3] and chronic cardiac failure [4]. We therefore investigated whether this stool test could be used to detect intestinal inflammation in a diagnostically challenging disease in which for the test period we could rule out any tumor involvement.

Faecal elastase-1 test is superior to faecal lipase test in the assessment of exocrine pancreatic function in cystic fibrosis.

Background and aims: Direct tests are characterized by the highest sensitivity and specificity. However, their practical use, especially in children, is limited. Among the indirect tests, the highest sensitivity and specificity was documented for faecal elastase‐1 test, yet the value of faecal lipase test in cystic fibrosis (CF) has not been defined. Therefore, the aim of the present study was to compare the sensitivity and the specificity of the faecal lipase test to the faecal elastase‐1 test in the assessment of exocrine pancreatic function in children with CF. Methods: The study comprised 90 CF patients and 95 healthy subjects (HS). In all subjects, faecal elastase‐1 concentrations (ELISA) and lipase activities (ELISA) were measured. The presence of pancreatic insufficiency was documented by the determination of faecal fat excretion in 78 pancreatic insufficient and by the secretin‐cholecystokinin test in 12 CF patients without steatorrhoea. Sensitivity and specificity of the faecal elastase‐1 test and faecal lipase test were analysed and, in 50 HS, sample‐to‐sample and day‐to‐day variations were determined. Results: With cut‐off levels providing the same specificity for both tests (95.8%), the sensitivity of the faecal elastase‐1 test (91.1%) was significantly higher (p > 0.0036) than that of the faecal lipase test (76.7%). Sample‐to‐sample (mean ± SEM: 13.2 ± 1.2% vs 23.4 ± 2.2%) and day‐to‐day variations (mean ± SEM: 16.3 ± 1.2% vs 32.5 ± 2.6%) were significantly lower (p > 0.0001) for elastase‐1 than for lipase measurements.