Pain in the Early Phase of Pediatric Pancreatitis (PINEAPPLE Trial): Pre-Study Protocol of a Multinational Prospective Clinical Trial.

BACKGROUND: There are unexpectedly large differences between the incidences of acute pancreatitis (AP) as indicated by different hospitals. Retrospective studies suggest that the reason behind this is the large differences that exist between the local managements of abdominal pain at emergency units. Unfortunately, no evidence-based medicine (EBM) guidelines are available to give proper instruction concerning the necessity of serum pancreatic enzyme measurement during abdominal pain. SUMMARY: Pain in Early Phase of Pediatric Pancreatitis (PINEAPPLE) is an observational, multinational observational clinical trial to explore the route from the first sign of abdominal pain to the diagnosis of pancreatitis (PINEAPPLE trial). The PINEAPPLE-R subtrial is a retrospective review on the records of children (patients under 18) appearing at emergency units - a review of their clinical symptoms, results of imaging examinations and laboratory parameters. The PINEAPPLE-P subtrial is a prospective trial designed to develop a fast and simple EBM guideline that helps to evaluate (in a reliable and cost-efficient way) the necessity of pancreatic enzyme test and abdominal ultrasonography (or even computed tomography) when a child has abdominal pain. The trial has been registered at the ISRCTN registry and has received the relevant ethical approval. KEY MESSAGE: The PINEAPPLE trial will help to recognize AP in children in a highly efficient manner.

Analysis of Pediatric Pancreatitis (APPLE Trial): Pre-Study Protocol of a Multinational Prospective Clinical Trial.

BACKGROUND: Single-centered studies show increased number of acute pancreatitis (AP) in children. Here, the Pediatric Section of the Hungarian Pancreatic Study Group introduces an international observational clinical trial (APPLE) to collect a critical mass of clinical data and biomedical research samples in a uniform prospective manner. SUMMARY: The APPLE-R is for patients under 18 years of age with a history of pancreatitis. The study primarily provides information on possible genetic variants behind the disease and their impact on the prognosis. The APPLE-P is for patients under 18 years of age with a diagnosis of AP. Children with AP diagnosed based on the fulfillment of '2 out of 3' of the Atlanta criteria will be selected. This subtrial requests detailed information from the medical history, etiology, complains and symptoms, physical examinations, laboratory parameters, imaging, immediate therapy at admission and complications of the disease. The APPLE trial has been registered at the ISRCTN registry and has received the relevant ethical approval. The study is open for all pediatric centers throughout the world. KEY MESSAGE: This is the first worldwide study tracking earlier (APPLE-R) and ongoing episodes (APPLE-P) of pancreatitis.

Genetic analysis of the bicarbonate secreting anion exchanger SLC26A6 in chronic pancreatitis.

BACKGROUND: Pancreatic ductal HCO3(-) secretion is critically dependent on the cystic fibrosis transmembrane conductance regulator chloride channel (CFTR) and the solute-linked carrier 26 member 6 anion transporter (SLC26A6). Deterioration of HCO3(-) secretion is observed in chronic pancreatitis (CP), and CFTR mutations increase CP risk. Therefore, SLC26A6 is a reasonable candidate for a CP susceptibility gene, which has not been investigated in CP patients so far. METHODS: As a first screening cohort, 106 subjects with CP and 99 control subjects with no pancreatic disease were recruited from the Hungarian National Pancreas Registry. In 60 non-alcoholic CP cases the entire SLC26A6 coding region was sequenced. In the Hungarian cohort variants c.616G > A (p.V206M) and c.1191C > A (p.P397=) were further genotyped by restriction fragment length polymorphism analysis. In a German replication cohort all exons were sequenced in 40 non-alcoholic CP cases and variant c.616G > A (p.V206M) was further analyzed by sequencing in 321 CP cases and 171 controls. RESULTS: Sequencing of the entire coding region revealed four common variants: intronic variants c.23 + 78_110del, c.183-4C > A, c.1134 + 32C > A, and missense variant c.616G > A (p.V206M) which were found in linkage disequilibrium indicating a conserved haplotype. The distribution of the haplotype did not show a significant difference between patients and controls in the two cohorts. A synonymous variant c.1191C > A (p.P397=) and two intronic variants c.1248 + 9_20del and c.-10C > T were detected in single cases. CONCLUSION: Our data show that SLC26A6 variants do not alter the risk for the development of CP.

[Autoimmune pancreatitis. Evidence based management guidelines of the Hungarian Pancreatic Study Group]. / Autoimmun pancreatitis. A Magyar Hasnyálmirigy Munkacsoport bizonyítékon alapuló kezelési irányelvei.

Autoimmune pancreatitis is a rare disease which can even mimic pancreatic tumor, however, unlike the latter, it requires not surgical but conservative management. Correct diagnosis and differential diagnosis of autoimmune pancreatitis and treatment of these patients requires up-to-date and evidence based management guidelines. The Hungarian Pancreatic Study Group proposed to prepare an evidence based guideline based on the available international guidelines and evidences. The preparatory and consultation task force appointed by the Hungarian Pancreatic Study Group translated and complemented and/or modified the international guidelines if it was necessary. 29 relevant clinical questions in 4 topics were defined (Basics; Diagnosis; Differential diagnostics; Therapy). Evidence was classified according to the UpToDate(®) grading system. The draft of the guidelines was presented and discussed at the consensus meeting on September 12, 2014. All clinial questions were accepted with almost total (more than 95%) agreement. The present guideline is the first evidence based autoimmune pancreatitis guideline in Hungary. The guideline may provide very important and helpful data for tuition of autoimmune pancreatitis, for everyday practice and for establishing proper finance. Therefore, the authors believe that these guidelines will widely become a basic reference in Hungary.

[Pediatric pancreatitis. Evidence based management guidelines of the Hungarian Pancreatic Study Group]. / Gyermekkori pancreatitis. A Magyar Hasnyálmirigy Munkacsoport bizonyítékon alapuló kezelési irányelvei.

Pediatric pancreatitis is a rare disease with variable etiology. In the past 10-15 years the incidence of pediatric pancreatitis has been increased. The management of pediatric pancreatitis requires up-to-date and evidence based management guidelines. The Hungarian Pancreatic Study Group proposed to prepare an evidence based guideline based on the available international guidelines and evidences. The preparatory and consultation task force appointed by the Hungarian Pancreatic Study Group translated and complemented and/or modified the international guidelines if it was necessary. In 8 clinical topics (diagnosis; etiology; prognosis; imaging; therapy; biliary tract management; complications; chronic pancreatitis) 50 relevant questions were defined. Evidence was classified according to the UpToDate(®) grading system. The draft of the guidelines was presented and discussed at the consensus meeting on September 12, 2014. All clinical statements were accepted with total (more than 95%) agreement. The present Hungarian Pancreatic Study Group guideline is the first evidence based pediatric pancreatitis guideline in Hungary. The present guideline is the first evidence-based pancreatic cancer guideline in Hungary that provides a solid ground for teaching purposes, offers quick reference for daily patient care in pediatric pancreatitis and guides financing options. The authors strongly believe that these guidelines will become a standard reference for pancreatic cancer treatment in Hungary.

[Pancreatic cancer. Evidence based management guidelines of the Hungarian Pancreatic Study Group]. / Pancreasrák. A Magyar Hasnyálmirigy Munkacsoport bizonyítékon alapuló kezelési irányelvei.

Pancreatic cancer is a disease with a poor prognosis usually diagnosed at a late stage. Therefore, screening, diagnosis, treatment and palliation of pancreatic cancer patients require up-to-date and evidence based management guidelines. The Hungarian Pancreatic Study Group proposed to prepare an evidence based guideline based on the available scientific evidence and international guidelines. The preparatory and consultation board appointed by the Hungarian Pancreatic Study Group translated and complemented/modified the recent international guidelines. 37 clinical statements in 10 major topics were defined (Risk factors and genetics, Screening, Diagnosis, Staging, Surgical care, Pathology, Systemic treatment, Radiation therapy, Palliation and supportive care, Follow-up and recurrence). Evidence was graded according to the National Comprehensive Cancer Network (NCCN) grading system. The draft of the guideline was presented and discussed at the consensus meeting in September 12, 2014. Statements were accepted with either total (more than 95% of votes, n = 15) or strong agreement (more than 70% of votes, n = 22). The present guideline is the first evidence-based pancreatic cancer guideline in Hungary that provides a solid ground for teaching purposes, offers quick reference for daily patient care and guides financing options. The authors strongly believe that these guidelines will become a standard reference for pancreatic cancer treatment in Hungary.

[Acute pancreatitis. Evidence-based practice guidelines, prepared by the Hungarian Pancreatic Study Group]. / Akut pancreatitis. A Magyar Hasnyálmirigy Munkacsoport bizonyítékon alapuló kezelési irányelvei.

Acute pancreatitis is one of the most common diseases of the gastrointestinal tract associated with significant morbidity and mortality that requires up-to-date and evidence based treatment guidelines. The Hungarian Pancreatic Study Group proposed to prepare evidence based guideline for the medical and surgical management of acute pancreatitis based on the available international guidelines and evidence. The preparatory and consultation task force appointed by the Hungarian Pancreatic Study Group translated and, if it was necessary, complemented and/or modified the international guidelines. All together 42 relevant clinical questions were defined in 11 topics (Diagnosis and etiology, Prognosis, Imaging, Fluid therapy, Intensive care management, Prevention of infectious complications, Nutrition, Biliary interventions, Post-endoscopic retrograde cholangio-pancreatography pancreatitis, Indication, timing and strategy for intervention in necrotizing pancreatitis, Timing of cholecystectomy [or endoscopic sphincterotomy]). Evidence was classified according to the UpToDate® grading system. The draft of the guideline was presented and discussed at the consensus meeting on September 12, 2014. 25 clinical questions with almost total (more than 95%) and 17 clinical questions with strong (more than 70%) agreement were accepted. The present guideline is the first evidence based acute pancreatitis guideline in Hungary. The guideline may provide important help for tuition, everyday practice and for establishment of proper finance of acute pancreatitis. Therefore, the authors believe that these guidelines will widely become as basic reference in Hungary.

[Chronic pancreatitis. Evidence based management guidelines of the Hungarian Pancreatic Study Group]. / Krónikus pancreatitis. A Magyar Hasnyálmirigy Munkacsoport bizonyítékon alapuló kezelési irányelvei.

Chronic pancreatitis is an inflammatory disease associated with structural and functional damage of the pancreas. In most cases pain, maldigestion and weight loss are the leading symptoms, which significantly worsen the quality of life. Correct diagnosis and differential diagnosis of chronic pancreatitis and treatment of these patients requires up-to-date and evidence based treatment guidelines. The Hungarian Pancreatic Study Group proposed to prepare an evidence based guideline based on the available international guidelines and evidence. The preparatory and consultation task force appointed by the Hungarian Pancreatic Study Group translated and complemented and/or modified the international guidelines if it was necessary. 123 relevant clinical questions in 11 topics were defined. Evidence was classified according to the UpToDate® grading system. The draft of the guidelines were presented and discussed at the consensus meeting in September 12, 2014. All clinical questions were accepted with total or strong agreement. The present guideline is the first evidence based guideline for chronic pancreatitis in Hungary. This guideline provides very important and helpful data for tuition, everyday practice and proper financing of chronic pancreatitis. Therefore, the authors believe that these guidelines will widely become a basic reference in Hungary.

Pancreatic family history does not predict disease progression but connotes alcohol consumption in adolescents and young adults with acute pancreatitis: Analysis of an international cohort of 2,335 patients.

Background: In pediatric acute pancreatitis (AP), a family history of pancreatic diseases is prognostic for earlier onset of recurrent AP (ARP) and chronic pancreatitis (CP). No evidence supports the same association in adult-onset pancreatitis. Age-specific reasons for familial aggregation are also unclear. We aimed to examine the prognostic role of pancreatic family history for ARP/CP and observe possible underlying mechanisms. Methods: We conducted a secondary analysis of the Hungarian Pancreatic Study Group's (HPSG) multicenter, international, prospective registry of patients with AP, both children and adults. We compared the positive family history and the negative family history of pancreatic diseases, in different age groups, and analyzed trends of accompanying factors. Chi-square and Fisher exact tests were used. Results: We found a higher rate of ARP/CP in the positive pancreatic family history group (33.7 vs. 25.9%, p = 0.018), peaking at 6-17 years. Idiopathic AP peaked in childhood in the positive family history group (75% 0-5 years) and was consistently 20-35% in the negative group. A higher rate of alcohol consumption/smoking was found in the positive groups at 12-17 years (62.5 vs. 15.8%, p = 0.013) and 18-29 years (90.9 vs. 58.1%, p = 0.049). The prevalence of diabetes and hyperlipidemia steadily rose with age in both groups. Conclusion: Positive family history most likely signifies genetic background in early childhood. During adolescence and early adulthood, alcohol consumption and smoking emerge-clinicians should be aware and turn to intervention in such cases. Contrary to current viewpoints, positive pancreatic family history is not a prognostic factor for ARP and CP in adults, so it should not be regarded that way.

[Is there a unique measuring method to assess obesity?]. / Van kitüntetett méromódszer az elhízás megállapítására?

UNLABELLED: In the literature there is not available a uniformly accepted method for assessing the degree of obesity. AIM: To determine how far insulin resistance, serum levels of leptin and resistin are altered in persons categorized on the basis of body-mass index (BMI), body fat percentage, and abdominal circumference. METHODS: 101 volunteer boys and 115 girls participated in the studies. Body height was measured, body mass, abdominal circumference, and body composition were determined by InBody3 bioimpedance instrument. Body mass index and body fat percentage were calculated by the instrument. Concentrations of serum glucose, insulin, leptin, and resistin were determined. Insulin resistance was calculated using the homeostasis model: HOMA IR . RESULTS: Body fat percentage, serum levels of leptin and resistin were significantly higher in girls than in boys. Increases in BMI, body fat percentage, and abdominal circumference were associated with the significant elevation of both HOMA IR and serum leptin concentrations. In overweight boys categorized by body fat percentage as obese the serum leptin concentrations were significantly higher than in their non-obese counterparts. CONCLUSION: Determination of body composition would be important concerning the follow-up of biochemical changes occurring in the body during the course of both epidemiological studies and nutritional interventions.

[Effects of oligofructose containing diet in obese persons]. / Az oligofruktóz hatásának vizsgálata elhízottakban.

UNLABELLED: In the treatment of obesity the introduction of a low-calorie diet is a fundamental requirement. The enhancement of the fiber content of food causing satiety may contribute to the observation of dietary prescriptions. Oligofructoses belong to the group of dietary fibers. AIM: To study the effects of the consumption of a low-energy diet (2,000 kcal/day) completed with Jerusalem artichoke concentrate in obese adolescents and adults. METHODS: 12 obese students (6 boys and 6 girls) and 6 obese women were put on a low-calorie regimen for 12 weeks, whereas 16 obese students (10 boys and 6 girls) and 17 obese women consumed the same low-calorie diet completed with Jerusalem artichoke concentrate containing 14 g/day oligofructose. Sensation of fullness was estimated. In addition to anthropometric parameters serum biomarkers of lipid and carbohydrate metabolism and adipokines were determined. RESULTS: The consumption of the low-calorie diet completed with Jerusalem artichoke concentrate resulted in a diminished sensation of hunger. Body mass index and body fat percentage decreased significantly. In girls and women, the serum levels of triglycerides were also significantly reduced and the rate of insulin resistance estimated on the basis of homeostasis model assessment was also improved. CONCLUSIONS: The results of this pilot study appear to demonstrate that the Jerusalem artichoke concentrate produced by a new technology can be a promising component of future diet therapy.

Effect of enterally administered n-3 polyunsaturated fatty acids in acute pancreatitis--a prospective randomized clinical trial.

BACKGROUND: In acute pancreatitis (AP) administration of n-3 polyunsaturated fatty acids (PUFAs) might change the course of the disease through modulation of eicosanoid synthesis. PATIENTS AND METHODS: In a prospective, randomized clinical trial from 28 patients with moderate-severe AP, 14 received n-3 PUFAs (fish oil) enterally (3.3g/day for 5-7 days). Measurement of erythrocyte superoxide-dysmutase (SOD) activity, serum total antioxidant status (TAS), vitamin A and E, fatty acids, C-reactive protein, transthyretin concentrations were performed at admission, day 3, 7 and 14. RESULTS: The n-3 to n-6 LCPUFA ratios increased significantly in serum lipids of the patients receiving n-3 PUFA supplementation, whereas remained unchanged in the controls. Supplementation resulted in significant decrease in length of hospitalization (13.07+/-6.70 vs. 19.28+/-7.18 days, P<0.05) and jejunal feeding (10.57+/-6.70 vs. 17.57+/-10.52, P<0.05). Complications developed in 6/14 (42%) of treated and 9/14 (64%) of control patients. The SOD activity was significantly higher at day 3 in the supplemented group (P<0.05), but there were no significant differences between the two groups in other antioxidants and acute phase reactants. CONCLUSION: The use of enteral formula enriched with n-3 PUFAs in the treatment of AP seems to have clinical benefits based upon the shortened time of jejunal feeding and hospital stay.

Protein status in pancreatitis--transthyretin is a sensitive biomarker of malnutrition in acute and chronic pancreatitis.

Malnutrition may develop in acute pancreatitis (AP), accompanied by hypermetabolism and high nutritional requirements, and in chronic pancreatitis (CP). We measured the incidence of protein malnutrition in AP and CP by comparing different serum biomarkers of protein metabolism and inflammation. Thirty-five patients with acute (27 moderate, 8 severe), and 35 with chronic, pancreatitis were enrolled in the study. Serum transthyretin, albumin, transferrin and C-reactive protein (CRP) concentrations were measured in AP at admission, after 1 and 2 weeks of jejunal feeding, and in patients with CP at follow-up. In AP, at admission the transthyretin level was low in 74%, transferrin in 48%, and albumin in 29% of patients. In severe pancreatitis, transthyretin levels were significantly lower than in moderate forms (7.5 +/- 2.43 vs. 14.39 +/- 6.8 mg/dl, p < 0.005). Transthyretin levels increased significantly after 2 weeks of jejunal feeding (p < 0.05). In CP, transthyretin levels were decreased in 37%, transferrin in 27%, and albumin in 12% of patients. We found significantly lower transthyretin levels in alcohol-related CPthan in other forms (18.5 +/- 8.3 vs. 30.2 +/- 5.7, p < 0.01). Transthyretin correlated positively with albumin and transferrin and negatively with CRP Transthyretin seems to be a sensitive biomarker of protein status and metabolic stress. Monitoring nutritional status through measurement of serum proteins is important for optimal treatment of AP and CP.