Ostre krwawienia z górnego odcinka przewodu pokarmowego o etiologii nieżylakowej: epidemiologia, etiologia i wyniki leczenia w Polsce w 2014 roku

Ostre krwawienia z górnego odcinka przewodu pokarmowego (GOPP) stanowią najczęstszy stan nagły w gastroenterologii. Na świecie występują z szacowaną roczną częstością wynoszącą 40/150 przypadków na 100 000 ludności. Większość z nich to krwawienia o tak zwanej etiologii nieżylakowej. W 16–20% przypadków w trakcie diagnostyki endoskopowej identyfikuje się więcej niż jedno źródło krwawienia, natomiast w 7–25% przypadków nie udaje się uwidocznić miejsca krwawienia w endoskopii. Ostre krwawienia z GOPP o etiologii nieżylakowej wymagają hospitalizacji częściej  niż krwawienia z dolnego odcinka przewodu pokarmowego, ponadto są potencjalną przyczyną zgonów. Leczenie powinno odbywać się w ośrodkach zapewniających odpowiedni sprzęt i przeszkoloną załogę. Celem artykułu jest oszacowanie skali zjawiska krwawień z GOPP w Polsce na podstawie danych pochodzących z Narodowego Funduszu Zdrowia, zebranych w 2014 roku. Omówiona zostanie częstość hospitalizacji, sposoby leczenia, nawrotowość krwawienia, konieczność transfuzji krwi oraz wskaźniki śmiertelności pacjentów

The natural history of primary sclerosing cholangitis in 781 children. A multicenter, international collaboration

There are limited data on the natural history of primary sclerosing cholangitis (PSC) in children. We aimed to describe the disease characteristics and long-term outcomes of pediatric PSC. We retrospectively collected all pediatric PSC cases from 36 participating institutions and conducted a survival analysis from the date of PSC diagnosis to dates of diagnosis of portal hypertensive or biliary complications, cholangiocarcinoma, liver transplantation, or death. We analyzed patients grouped by disease phenotype and laboratory studies at diagnosis to identify objective predictors of long-term outcome. We identified 781 patients, median age 12 years, with 4,277 person-years of follow-up; 33% with autoimmune hepatitis, 76% with inflammatory bowel disease, and 13% with small duct PSC. Portal hypertensive and biliary complications developed in 38% and 25%, respectively, after 10 years of disease. Once these complications developed, median survival with native liver was 2.8 and 3.5 years, respectively. Cholangiocarcinoma occurred in 1%. Overall event-free survival was 70% at 5 years and 53% at 10 years. Patient groups with the most elevated total bilirubin, gamma-glutamyltransferase, and aspartate aminotransferase-to-platelet ratio index at diagnosis had the worst outcomes. In multivariate analysis PSC-inflammatory bowel disease and small duct phenotypes were associated with favorable prognosis (hazard ratios 0.6, 95% confidence interval 0.5-0.9, and 0.7, 95% confidence interval 0.5-0.96, respectively). Age, gender, and autoimmune hepatitis overlap did not impact long-term outcome. CONCLUSION: PSC has a chronic, progressive course in children, and nearly half of patients develop an adverse liver outcome after 10 years of disease; elevations in bilirubin, gamma-glutamyltransferase, and aspartate aminotransferase-to-platelet ratio index at diagnosis can identify patients at highest risk; small duct PSC and PSC-inflammatory bowel disease are more favorable disease phenotypes

Assessing the Validity of Adult-derived Prognostic Models for Primary Sclerosing Cholangitis Outcomes in Children

Background: Natural history models for primary sclerosing cholangitis (PSC) are derived from adult patient data, but have never been validated in children. It is unclear how accurate such models are for children with PSC. Methods: We utilized the pediatric PSC consortium database to assess the Revised Mayo Clinic, Amsterdam-Oxford, and Boberg models. We calculated the risk stratum and predicted survival for each patient within each model using patient data at PSC diagnosis, and compared it with observed survival. We evaluated model fit using the c-statistic. Results: Model fit was good at 1 year (c-statistics 0.93, 0.87, 0.82) and fair at 10 years (0.78, 0.75, 0.69) in the Mayo, Boberg, and Amsterdam-Oxford models, respectively. The Mayo model correctly classified most children as low risk, whereas the Amsterdam-Oxford model incorrectly classified most as high risk. All of the models underestimated survival of patients classified as high risk. Albumin, bilirubin, AST, and platelets were most associated with outcomes. Autoimmune hepatitis was more prevalent in higher risk groups, and over-weighting of AST in these patients accounted for the observed versus predicted survival discrepancy. Conclusions: All 3 models offered good short-term discrimination of outcomes but only fair long-term discrimination. None of the models account for the high prevalence of features of autoimmune hepatitis overlap in children and the associated elevated aminotransferases. A pediatric-specific model is needed. AST, bilirubin, albumin, and platelets will be important predictors, but must be weighted to account for the unique features of PSC in children.Peer reviewe

Recurrence of Primary Sclerosing Cholangitis After Liver Transplant in Children : An International Observational Study

Background and Aims Recurrent primary sclerosing cholangitis (rPSC) following liver transplant (LT) has a negative impact on graft and patient survival; little is known about risk factors for rPSC or disease course in children. Approach and Results We retrospectively evaluated risk factors for rPSC in 140 children from the Pediatric PSC Consortium, a multicenter international registry. Recipients underwent LT for PSC and had >90 days of follow-up. The primary outcome, rPSC, was defined using Graziadei criteria. Median follow-up after LT was 3 years (interquartile range 1.1-6.1). rPSC occurred in 36 children, representing 10% and 27% of the subjects at 2 years and 5 years following LT, respectively. Subjects with rPSC were younger at LT (12.9 vs. 16.2 years), had faster progression from PSC diagnosis to LT (2.5 vs. 4.1 years), and had higher alanine aminotransferase (112 vs. 66 IU/L) at LT (all P < 0.01). Inflammatory bowel disease was more prevalent in the rPSC group (86% vs. 66%; P = 0.025). After LT, rPSC subjects had more episodes of biopsy-proved acute rejection (mean 3 vs. 1; P < 0.001), and higher prevalence of steroid-refractory rejection (41% vs. 20%; P = 0.04). In those with rPSC, 43% developed complications of portal hypertension, were relisted for LT, or died within 2 years of the diagnosis. Mortality was higher in the rPSC group (11.1% vs. 2.9%; P = 0.05). Conclusions The incidence of rPSC in this cohort was higher than previously reported, and was associated with increased morbidity and mortality. Patients with rPSC appeared to have a more aggressive, immune-reactive phenotype. These findings underscore the need to understand the immune mechanisms of rPSC, to lay the foundation for developing new therapies and improve outcomes in this challenging population.Peer reviewe

Endoscopic therapy of oesophageal strictures in children : a multicentre study

Introduction: Oesophageal strictures are rare in children but may require endoscopic dilation. Aim: To gather information on centres performing endoscopic oesophageal dilation in Poland. Material and methods: The data were obtained from questionnaires concerning the relevant data mailed to 22 paediatric endoscopy centres. Completed questionnaires were received from 11 centres. Results: In 2010 the 11 Polish paediatric endoscopy centres performed a total of 10,650 endoscopic procedures. This included 347 oesophageal dilations in 106 paediatric patients aged from 1 month to 18 years. The numbers of patients treated at individual centres ranged from 2 to 40. The indications for oesophageal dilation were as follows: postoperative strictures in 68 children, oesophageal burns in 17 children, postinflammatory strictures in 14 children, achalasia in 4 children, and strictures caused by a foreign body in 3 children. Rigid guidewire dilators were used in the majority of procedures (271), rigid dilators without a guidewire in 32 procedures, and balloon dilators in 45 procedures. A total of 203 procedures were conducted under fluoroscopic guidance, and 144 without the use of fluoroscopy. The number of dilating sessions performed in individual children varied from 1 to 6 and more. Conclusions: Oesophageal dilation constituted a minor proportion of all paediatric endoscopic procedures. The majority of children requiring dilation were patients up to 3 years of age with postoperative oesophageal strictures. In the majority of the centres rigid guidewire dilators were used, and in one third of the procedures these dilators were introduced without fluoroscopic guidance

Lack of an association between Helicobacter infection and autoimmune hepatitis in children

An association between Helicobacter infection and autoimmune hepatitis (AIH) in children was investigated. The prevalence of antibodies to H. pylori did not differ between the AIH and the control group, (22% versus 14%), and antibodies to non-gastric Helicobacter were not detected in either group. H. pylori DNA was found in two AIH liver tissues, but Helicobacter was not cultured from any sample

Transcriptional and Ultrastructural Analyses Suggest Novel Insights into Epithelial Barrier Impairment in Celiac Disease

Disruption of epithelial junctional complex (EJC), especially tight junctions (TJ), resulting in increased intestinal permeability, is supposed to activate the enhanced immune response to gluten and to induce the development of celiac disease (CD). This study is aimed to present the role of EJC in CD pathogenesis. To analyze differentially expressed genes the next-generation mRNA sequencing data from CD326+ epithelial cells isolated from non-celiac and celiac patients were involved. Ultrastructural studies with morphometry of EJC were done in potential CD, newly recognized active CD, and non-celiac controls. The transcriptional analysis suggested disturbances of epithelium and the most significant gene ontology enriched terms in epithelial cells from CD patients related to the plasma membrane, extracellular exome, extracellular region, and extracellular space. Ultrastructural analyses showed significantly tighter TJ, anomalies in desmosomes, dilatations of intercellular space, and shorter microvilli in potential and active CD compared to controls. Enterocytes of fetal-like type and significantly wider adherence junctions were observed only in active CD. In conclusion, the results do not support the hypothesis that an increased passage of gluten peptides by unsealing TJ precedes CD development. However, increased intestinal permeability due to abnormality of epithelium might play a role in CD onset

Interobserver Agreement on Endoscopic Classification of Oesophageal Varices in Children

Data regarding agreement on endoscopic features of oesophageal varices in children with portal hypertension (PH) are scant. The aim of this study was to evaluate endoscopic visualisation and classification of oesophageal varices in children by several European clinicians, to build a rational basis for future multicentre trials