István Hritz

Early ERCP and biliary sphincterotomy with or without small-caliber pancreatic stent insertion in patients with acute biliary pancreatitis: better overall outcome with adequate pancreatic drainage

Abstract Objective. To analyze the efficacy of pancreatic duct (PD) stenting following endoscopic sphincterotomy (EST) compared with EST alone in reducing complication rate and improving overall outcome in acute biliary pancreatitis (ABP). Methods. Between 1 January 2009 and 1 July 2010, 141 nonalcoholic patients with clinical, laboratory and imaging evidence of ABP were enrolled. Emergency endoscopic retrograde cholangiopancreatography (ERCP) was performed within 72 h from the onset of pain. Seventy patients underwent successful ERCP, EST, and stone extraction (control group); 71 patients (PD stent group) had EST, stone extraction and small-caliber (5 Fr, 3-5 cm) pancreatic stent insertion. All patients were hospitalized for medical therapy and jejunal feeding and were followed up. Results. The mean age, Glasgow score, symptom to ERCP time, mean amylase and CRP levels at initial presentation were not significantly different in the PD stent group compared to the control group: 60.6 vs. 64.3, 3.21 vs. 3.27, 34.4 vs. 40.2, 2446.9 vs. 2114.3, 121.1 vs. 152.4, respectively. Complications (admission to intensive care unit, pancreatic necrosis with septicemia, large (>6 cm) pseudocyst formation, need for surgical necrosectomy) were less frequent in the PD stent group resulting in a significantly lower overall complication rate (9.86% vs. 31.43%, p < 0.002). Mortality rates (0% vs. 4.28%) were comparable, reasonably low and without any significant differences. Conclusions. Temporary small-caliber PD stent placement may offer sufficient drainage to reverse the process of ABP. Combined with EST the process results in a significantly less complication rate and better clinical outcome compared with EST alone during the early course of ABP.

Prospective, Multicentre, Nationwide Clinical Data from 600 Cases of Acute Pancreatitis

Objective The aim of this study was to analyse the clinical characteristics of acute pancreatitis (AP) in a prospectively collected, large, multicentre cohort and to validate the major recommendations in the IAP/APA evidence-based guidelines for the management of AP. Design Eighty-six different clinical parameters were collected using an electronic clinical research form designed by the Hungarian Pancreatic Study Group. Patients 600 adult patients diagnosed with AP were prospectively enrolled from 17 Hungarian centres over a two-year period from 1 January 2013. Main Results With respect to aetiology, biliary and alcoholic pancreatitis represented the two most common forms of AP. The prevalence of biliary AP was higher in women, whereas alcoholic AP was more common in men. Hyperlipidaemia was a risk factor for severity, lack of serum enzyme elevation posed a risk for severe AP, and lack of abdominal pain at admission demonstrated a risk for mortality. Abdominal tenderness developed in all the patients with severe AP, while lack of abdominal tenderness was a favourable sign for mortality. Importantly, lung injury at admission was associated with mortality. With regard to laboratory parameters, white blood cell count and CRP were the two most sensitive indicators for severe AP. The most common local complication was peripancreatic fluid, whereas the most common distant organ failure in severe AP was lung injury. Deviation from the recommendations in the IAP/APA evidence-based guidelines on fluid replacement, enteral nutrition and timing of interventions increased severity and mortality. Conclusions Analysis of a large, nationwide, prospective cohort of AP cases allowed for the identification of important determinants of severity and mortality. Evidence-based guidelines should be observed rigorously to improve outcomes in AP.

Chronic pancreatitis. Evidence based management guidelines of the Hungarian Pancreatic Study Group

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.

Pediatric pancreatitis. Evidence based management guidelines of the Hungarian Pancreatic Study Group

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.

SPINK1 Promoter Variants in Chronic Pancreatitis.

Objectives Serine protease inhibitor Kazal type 1 (SPINK1) provides an important line of defense against premature trypsinogen activation within the pancreas. Our aim was to identify pathogenic SPINK1 promoter variants associated with chronic pancreatitis (CP). Methods One hundred CP patients (cases) and 100 controls with no pancreatic disease from the Hungarian National Pancreas Registry were enrolled. Direct sequencing of SPINK1 promoter region was performed. Functional characterization of variants was carried out using luciferase reporter gene assay. Results Two common polymorphisms (c.-253T>C and c.-807C>T) were found in both cases and controls. Variant c.253T>C was enriched in cases relative to controls (odds ratio, 2.1; 95% confidence interval, 1.2-3.8; P = 0.015). Variant c.-215G>A was detected in 3 of 100 cases; always linked with the pathogenic variant c.194+2T>C. Novel promoter variants c.-14G>A, c.-108G>T, and c.-246A>G were identified in 1 case each. Functional analysis showed decreased promoter activity for variants c.-14G>A (80%), c.-108G>T (31%), and c.-246A>G (47%) whereas activity of variant c.-215G>A was increased (201%) and variant c.-253T>C was unchanged compared with wild type. Conclusions The common promoter variant c.-253T>C was associated with CP in this cohort. Two of 3 newly identified SPINK1 promoter variants seem to exhibit significant functional defects and should be considered potential risk factors for CP.

Pancreatic cancer. Evidence based management guidelines of the Hungarian Pancreatic Study Group

A pancreasrak gyakran kesőn diagnosztizalt korkep, amely a legrosszabb korlefolyasu betegsegek csoportjaba sorolhato, ezert a szűrese, diagnosztikaja, kezelese es palliacioja korszerű es bizonyitekokon alapulo utmutatot igenyel. A Magyar Hasnyalmirigy Munkacsoport celul tűzte ki, hogy a jelenleg elerhető nemzetkozi iranyvonalakat, illetve evidenciakat alapul veve a pancreasrak kezelesenek kulcskerdesei vonatkozasaban bizonyitek alapu iranyelveket fogalmazzon meg. A Magyar Hasnyalmirigy Munkacsoport altal kijelolt előkeszitő es konzulens munkacsoport leforditotta, es ahol szuksegesnek talalta, kiegeszitette es/vagy modositotta a nemzetkozi iranyelveket. Osszesen 10 temakorben (Rizikofaktorok es genetika, Szűres, Diagnozis, Staging, Sebeszi kezeles, Patologiai feldolgozas, Szisztemas kezeles, Sugarterapia, Palliacio es szupportiv kezeles, Utankovetes es rekurrencia) 37 relevans iranyelv kerult osszeallitasra. Az evidencia osztalyozasa a National Comprehensive Cancer Network (NCCN) rendszere alapjan kerult meghatarozasra. Az osszeallitott iranyelvek a 2014. szeptember 12-ei konszenzustalalkozon kerultek bemutatasra es megvitatasra. A resztvevők 15 iranyelvet teljes (95% feletti) egyetertessel, mig 22 iranyelvet erős (70% feletti) egyetertessel fogadtak el. A Magyar Hasnyalmirigy Munkacsoport kezelesi iranyelvei az első, bizonyitek alapjan keszult pancreasrak-kezelesi utmutato hazankban. Az iranyelv komoly segitseget nyujthat a pancreasrak oktatasahoz, a mindennapi betegellatashoz es a megfelelő finanszirozas kialakitasahoz. Ezert a szerzők biznak abban, hogy ezen iranyelvek minel szelesebb korben alapreferenciakent fognak szolgalni Magyarorszagon. Orv. Hetil., 2015, 156(8), 326–339.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.

Preventive pancreatic stents in the management of acute biliary pancreatitis (PREPAST trial): Pre-study protocol for a multicenter, prospective, randomized, interventional, controlled trial

BACKGROUNDnThe outcome of the most common biliary form of acute pancreatitis has not changed even with the better described indications for early endoscopic intervention. It may be due to the fact that this intrevention theoretically can cause further pancreatic injury or cannot always relieve the pancreatic duct obstruction. We hypothesize that maintaining the outflow of the pancreatic duct with preventive pancreatic stents at the early ERCP improves the outcome of acute biliary pancreatitis.nnnMETHODS/DESIGNnPREPAST is a prospective, randomized, controlled, multicenter trial. Patients with acute biliary pancreatitis with coexisting cholangitis are randomized to undergo urgent endoscopic intervention with or without pancreatic stenting within 48xa0h from the onset of pain, and in addition patients without signs of cholangitis but cholestasis are randomly allocated to recieve conservative treatment or early endoscopic intervention with or without pancreatic stenting within 48xa0h from the onset of pain. Patients without acute cholangitis and signs of cholestasis recieve conservative treatment. 230 patients are planned to be enrolled during a 48 months period from different centers. The primary endpoint is the outcome of acute biliary pancreatitis as described by the latest guidelines. Secondary endpoints include mortality data, and other variables not analyzed as a primary endpoint but related to the pancreatitis or the pancreatic stenting.nnnDISCUSSIONnThe PREPAST trial is designed to show whether early endoscopic intervention with the usage of preventive pancreatic stenting improves the outcome of acute biliary pancreatitis. The study has been registered at the International Standard Randomised Controlled Trial Number (ISRCTN) Register (trial ID: ISRCTN13517695).

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

BACKGROUNDnPancreatic 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.nnnMETHODSnAs 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.616Gxa0>xa0A (p.V206M) and c.1191Cxa0>xa0A (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.616Gxa0>xa0A (p.V206M) was further analyzed by sequencing in 321 CP cases and 171 controls.nnnRESULTSnSequencing of the entire coding region revealed four common variants: intronic variants c.23xa0+xa078_110del, c.183-4Cxa0>xa0A, c.1134xa0+xa032Cxa0>xa0A, and missense variant c.616Gxa0>xa0A (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.1191Cxa0>xa0A (p.P397=) and two intronic variants c.1248xa0+xa09_20del and c.-10Cxa0>xa0T were detected in single cases.nnnCONCLUSIONnOur data show that SLC26A6 variants do not alter the risk for the development of CP.

A Common CCK-B Receptor Intronic Variant in Pancreatic Adenocarcinoma in a Hungarian Cohort:

Objectives Variant c.811+32C>A in intron 4 of the cholecystokinin-B receptor gene (CCKBR) was reported to correlate with higher pancreatic cancer risk and poorer survival. The variant was suggested to induce retention of intron 4, resulting in a new splice form with enhanced receptor activity. Our objective was to validate the c.811+32C>A variant as an emerging biomarker for pancreatic cancer risk and prognosis. Methods We genotyped variant c.811+32C>A in 122 pancreatic adenocarcinoma case patients and 106 control subjects by sequencing and examined its association with cancer risk and patient survival. We tested the functional effect of variant c.811+32C>A on pre–messenger RNA splicing in human embryonic kidney 293T and Capan-1 cells transfected with CCKBR minigenes. Results The allele frequency of the variant was similar between patients and control subjects (18.4% and 17.9%, respectively). Survival analysis showed no significant difference between median survival of patients with the C/C genotype (266 days) and patients with the A/C or A/A genotypes (257 days). CCKBR minigenes with or without variant c.811+32C>A exhibited no difference in expression of the intron-retaining splice variant. Conclusion These data indicate that variant c.811+32C>A in CCKBR does not have a significant impact on pancreatic cancer risk or survival in a Hungarian cohort.