Michal Rygl

European biliary atresia registries: summary of a symposium.

Biliary atresia (BA) is a rare but potentially devastating disease. The European Biliary Atresia Registry (EBAR) was set up to improve data collection and to develop a pan-national and interdisciplinary strategy to improve clinical outcomes. From 2001 to 2005, 100 centers from 22 countries registered with EBAR via its website (www.biliary-atresia.com). In June 2006, the first meeting was held to evaluate results and launch further initiatives. During a 5-year period, 60 centers from 19 European countries and Israel sent completed registration forms for a total of 514 BA patients. Assuming the estimated incidence of BA in Europe is 1:18,000 live births, 35% of the expected 1488 patients from all EBAR participating countries were captured, suggesting that reporting arrangements need improvement. At the meeting, the cumulative evaluation of 928 BA patients including patients from other registries with variable follow-up revealed an overall survival of 78% (range from 41% to 92%), of whom 342 patients (37%) have had liver transplants. Survival with native liver ranged from 14% to 75%. There was a marked variance in reported management and outcome by country (e.g., referral patterns, timing of surgery, centralization of surgery). In conclusion, EBAR represents the first attempt at an overall evaluation of the outcome of BA from a pan-European perspective. The natural history and outcome of biliary atresia is of considerable relevance to a European population. It is essential that there is further support for a pan-European registry with coordination of clinical standards, further participation of parent support groups, and implementation of online data entry and multidisciplinary clinical and basic research projects.

What is the role of endoscopic retrograde cholangiopancreatography in assessing traumatic rupture of the pancreatic in children

Abstract Background and study aims: Trauma is one of the most common causes of morbidity and mortality in the pediatric population. The diagnosis of pancreatic injury is based on clinical presentation, laboratory and imaging findings, and endoscopic methods. CT scanning is considered the gold standard for diagnosing pancreatic trauma in children. Patients and methods: This retrospective study evaluates data from 25 pediatric patients admitted to the University Hospital Motol, Prague, with blunt pancreatic trauma between January 1999 and June 2013. Results: The exact grade of injury was determined by CT scans in 11 patients (47.8%). All 25 children underwent endoscopic retrograde cholangiopancreatography (ERCP). Distal pancreatic duct injury (grade III) was found in 13 patients (52%). Proximal pancreatic duct injury (grade IV) was found in four patients (16 %). Major contusion without duct injury (grade IIB) was found in six patients (24%). One patient experienced duodeno-gastric abruption not diagnosed on the CT scan. The diagnosis was made endoscopically during ERCP. Grade IIB pancreatic injury was found in this patient. One patient (4%) with pancreatic pseudocyst had a major contusion of pancreas without duct injury (grade IIA). Four patients (16%) with grade IIB, III and IV pancreatic injury were treated exclusively and nonoperatively with a pancreatic stent insertion and somatostatine. Two patients (8%) with a grade IIB injury were treated conservatively only with somatostatine without drainage. Eighteen (72 %) children underwent surgical intervention within 24 h after ERCP. Conclusion: ERCP is helpful when there is suspicion of pancreatic duct injury in order to exclude ductal leakage and the possibility of therapeutic intervention. ERCP can speed up diagnosis of higher grade of pancreatic injuries.

Alagille Syndrome Mimicking Biliary Atresia in Early Infancy.

Alagille syndrome may mimic biliary atresia in early infancy. Since mutations in JAG1 typical for Alagille syndrome type 1 have also been found in biliary atresia, we aimed to identify JAG1 mutations in newborns with proven biliary atresia (n = 72). Five biliary atresia patients with cholestasis, one additional characteristic feature of Alagille syndrome and ambiguous liver histology were single heterozygotes for nonsense or frameshift mutations in JAG1. No mutations were found in the remaining 67 patients. All “biliary atresia” carriers of JAG1 null mutations developed typical Alagille syndrome at the age of three years. Our data do not support association of biliary atresia with JAG1 mutations, at least in Czech patients. Rapid testing for JAG1 mutations could prevent misdiagnosis of Alagille syndrome in early infancy and improve their outcome.

Parameters of healing in approximative intestinal anastomosis.

INTRODUCTION The restoration of bowel continuity using multiple classic anastomoses is mostly impossible in unstable critically ill extremely low birth weight neonates. The parameters of healing of approximative anastomoses in which integrity and continuity of bowel is achieved with limited number of stitches were evaluated in an experimental study. MATERIAL AND METHODS Small bowel anastomoses were performed in twenty-two adult male rats. An approximative ileo-ileal anastomosis was performed with five seromuscular-interrupted sutures only; in the control group the anastomosis was performed with the conventional technique of interrupted sutures. The mechanical and biochemical parameters were compared. RESULTS All anastomoses in both groups healed well without obstruction. The mean operating time needed for an approximative anastomosis was shorter (16 +/- 7.1 min versus 23.6 +/- 6.2 min, p = 0.016). The strength of the approximative anastomoses on the 1st day after surgery was 55 +/- 15 torr; the strength of the conventional anastomoses was 55 +/- 42 torr. The strength of the approximative anastomoses after 7 days was 249 +/- 39 torr; the strength of the conventional anastomoses was 218 +/- 23 torr (p = 0.118). The activity of the collagenolytic enzymes matrix metalloproteinase-2 and matrix metalloproteinase-9 in the anastomotic area was significantly increased compared with the activity in samples of non-operated bowel. There was no significant difference in collagenolytic activity between both types of anastomoses. CONCLUSION The approximative anastomosis is a time-saving alternative to conventional anastomoses with a comparable course of anastomotic healing, anastomotic strength, and changes in collagen metabolism.

Antenatal assessment of liver position, rather than lung-to-head ratio (LHR) or observed/expected LHR, is predictive of outcome in fetuses with isolated left-sided congenital diaphragmatic hernia.

Abstract Objectives: Respiratory morbidity in congenital diaphragmatic hernia (CDH) is associated with high mortality and adverse outcome. Accurate prenatal diagnosis is essential for prognosis and potential treatment in utero. The aim was to evaluate the prenatal ultrasound findings in assessing the respiratory prognosis in fetuses with isolated left-sided CDH. Methods: We retrospectively analyzed the medical records of 59 prenatally diagnosed left-sided CDH cases managed at a tertiary perinatal center. Results: Survival rate in the study group was 73% (43/59). We found no statistically significant relationship between survival and the presence of polyhydramnios, gestational age at diagnosis, lung-to-head ratio (LHR) and observed/expected LHR (O/E LHR) values, gestational age at birth and birth weight. Intrathoracic liver herniation was a statistically significant parameter adversely affecting survival (37.2% in survivors, 68.8% in non-survivors, p = 0.031) and logistic regression confirmed this relationship. The presence of pneumothorax and severe pulmonary hypertension were significantly associated with mortality (82% non-survivors versus 15% in survivors, p = 0.0001). Conclusion: Intrathoracic liver herniation seems to be a reliable parameter in the prediction of survival and neonatal respiratory morbidity in fetuses with isolated left-sided CDH. In contrast, we found no significant correlation between perinatal outcome and LHR, O/E LHR values, birth weight and gestational age.

Urinary Intestinal Fatty Acid-Binding Protein Can Distinguish Necrotizing Enterocolitis from Sepsis in Early Stage of the Disease

Necrotizing enterocolitis (NEC) is severe disease of gastrointestinal tract, yet its early symptoms are nonspecific, easily interchangeable with sepsis. Therefore, reliable biomarkers for early diagnostics are needed in clinical practice. Here, we analyzed if markers of gut mucosa damage, caspase cleaved cytokeratin 18 (ccCK18) and intestinal fatty acid-binding protein (I-FABP), could be used for differential diagnostics of NEC at early stage of disease. We collected paired serum (at enrollment and week later) and urine (collected for two days in 6 h intervals) samples from 42 patients with suspected NEC. These patients were later divided into NEC (n = 24), including 13 after gastrointestinal surgery, and sepsis (n = 18) groups using standard criteria. Healthy infants (n = 12), without any previous gut surgery, served as controls. Both biomarkers were measured by a commercial ELISA assay. There were no statistically significant differences in serum ccCK18 between NEC and sepsis but NEC patients had significantly higher levels of serum and urinary I-FABP than either sepsis patients or healthy infants. Urinary I-FABP has high sensitivity (81%) and specificity (100%) and can even distinguish NEC from sepsis in patients after surgery. Urinary I-FABP can be used to distinguish NEC from neonatal sepsis, including postoperative one, better than abdominal X-ray.

Abnormalities in pulmonary function in infants with high-risk congenital diaphragmatic hernia

AIMS The aim of the study was to analyze lung growth and abnormality of infant pulmonary function tests (IPFT) in congenital diaphragmatic hernia (CDH) survivors younger than three years of age with respect to unfavorable prognostic factors. METHODS Thirty high-risk CDH survivors at the age of 1.32±0.54 years, body weight 9.76±1.25 kg were examined using IPFT: tidal breathing analysis, baby resistance/compliance, whole baby body plethysmography and rapid thoraco-abdominal compression. Gore-Tex patch was used in 13% of patients (GORE group). Pulmonary hypertension was diagnosed and managed in 13% (iNO group). Standard protocols and appropriate reference values were used and obtained data were statistically analysed. RESULTS High incidence of peripheral airway obstruction (70%), increased value of functional residual capacity (FRCp) 191.3±24.5 mL (126.5±36.9 % predicted; P < 0.0005), increased value of effective airway resistance (Reff) 1.71±0.93 kPa.L(-1).s (144.4±80.1 % predicted; P < 0.01) and decreased specific compliance of the respiratory system (Crs/kg) 14.1±2.3 mL.kPa.kg(-1) (i.e., 76.1±20.1 % predicted, P < 0.0005) was noted in infants with CDH in comparison with reference values. Increased value of FRCp was found in GORE group (165.7±51.9 versus 120.4±31.2, P < 0.02) and in iNO group (183.1±52.6 versus 117.8±25.7 mL; P < 0.0005). CONCLUSION A high incidence of peripheral airway obstruction, an increased value of FRCp and decreased specific compliance of the respiratory system was noted in infants with CDH. Unfavorable prognostic factors (Gore-Tex patch, pulmonary hypertension) correlate with more severe alteration of pulmonary function in infants.

The role of endoscopic retrograde cholangiopancreatography in choledochal cysts and/or abnormal pancreatobiliary junction in children

Introduction Biliary cysts with an abnormal pancreatobiliary junction are one of the most common pancreatobiliary malformations. The main symptom is cholestasis; endoscopic retrograde cholangiopancreatography (ERCP) plays a key role in diagnosis. Aim Retrospective evaluation of ERCP performed to diagnose abnormalities of the pancreatobiliary junction. Material and methods We retrospectively evaluated ERCP performed to diagnose abnormalities of the pancreatobiliary junction, mainly choledochal cysts, in 112 children between 1990 and 2011. Results We performed 112 examinations of 50 children with abnormal pancreatobiliary junction and choledochal cysts (15 males and 35 females, average age: 5 years, range: 1 month – 15 years). Cysts were associated with a common channel in 37 (74%) cases, were not associated with a common channel in 9 (18%) cases, and in 3 (6%) cases the common channel lacked cysts. We performed endoscopic papilla sphincterotomy on 33 (66%) patients; endoscopic drainage was performed 62 times, including 17 patients without papilla sphincterotomy. In 15 (30%) cases, we only performed sphincterotomy. Extraction of lithiasis was done in 2 (4%) cases. Both ERCP and magnetic resonance cholangiopancreatography (MRCP) were performed on 13 patients. There was concordance of the choledochal cyst and of the type of cyst in both methods; however, common channels could not be observed by MRCP. There was 1 serious complication (perforation after sphincterotomy) and 11 (9%) mild adverse events. Conclusions When performed at an expert centre, ECRP is a safe and reliable procedure for children with choledochal cysts and/or an abnormal pancreatobiliary junction. Endoscopic retrograde cholangiopancreatography remains a reasonable alternative because MRCP has a limited ability to diagnose the precise anomalies of the pancreatobiliary junction and has no therapeutic capabilities.

Delayed diagnosis of a right-sided traumatic diaphragmatic rupture

Right-sided traumatic diaphragmatic rupture in childhood is a very rare injury. Diaphragmatic rupture often manifests itself later, after an organ progressively herniates into the pleural cavity. When the patient is tubed, the ventilation pressure does not allow herniation of an organ, which occurs when the patient is ex-tubed. We present a patient with a delayed diagnose of right sided diaphragmatic rupture with a complicated post-operation state.

Cholelithiasis and choledocholithiasis in children; risk factors for development

Purpose To compare anthropometric data (body mass index [BMI]) in patients without lithiasis to patients with symptomatic simple cholelithiasis or choledocholithiasis. Methods We retrospectively reviewed data from 147 patients undergoing laparoscopic cholecystectomy between 2001–2015. Complete growth data from 98 patients was compared with anthropometric data from the population of the Czech Republic and a control group (BMI of 100 consecutive patients without biliary stones in abdominal ultrasound who were admitted to a surgical department for suspected appendicitis). Results The BMI of 75 children with simple cholelithiasis and 23 with choledocholithiasis was compared to the standard Czech pediatric population and to the control group. The median age (simple cholelithiasis and choledocholithiasis) was 16 years, and 35 patients (24%) had a family history of gallstones. Types of lithiasis included multiple (n = 120), solitary (n = 11), and sludge (n = 10). Five cases had polyps and one had gallbladder dysplasia. Patients with simple cholelithiasis had significantly higher BMI compared to the control group without cholelithiasis (p<0.0001) and the standard Czech population (p = 0.03). Patients with choledocholithiasis had a mean BMI significantly higher than that of the general population (p = 0.001) and the control group (p = 0.0001). Patients with choledocholithiasis had significantly higher BMI than those with simple cholelithiasis (p = 0.03). Conclusion Patients with cholelithiasis had significantly higher BMI than the general population, and patients with choledocholithiasis had significantly higher BMI than patients with simple lithiasis. Elevated BMI is a risk factor for developing choledocholithiasis. ERCP and early laparoscopic cholecystectomy in patients with choledocholithiasis offer equivalent outcomes in patients with simple cholelithiasis.