Dezső Kelemen

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.

Pancreatic Cancer: Multicenter Prospective Data Collection and Analysis by the Hungarian Pancreatic Study Group.

BACKGROUND AND AIMS Pancreatic cancer is a devastating disease with poor prognosis. There is very limited information available regarding the epidemiology and treatment strategies of pancreatic cancer in Central Europe. The purpose of the study was to prospectively collect and analyze data of pancreatic cancer in the Hungarian population. METHODS The Hungarian Pancreatic Study Group (HPSG) organized prospective, uniform data collection. Altogether 354 patients were enrolled from 14 Hungarian centers. RESULTS Chronic pancreatitis was present in 3.7% of the cases, while 33.7% of the patients had diabetes. Family history for pancreatic cancer was positive in 4.8%. The most frequent presenting symptoms included pain (63.8%), weight loss (63%) and jaundice (52.5%). The reported frequency of smoking and alcohol consumption was lower than expected (28.5% and 27.4%, respectively). The majority of patients (75.6%) were diagnosed with advanced disease. Most patients (83.6%) had a primary tumor located in the pancreatic head. The histological diagnosis was ductal adenocarcinoma in 90.7% of the cases, while neuroendocrine tumor was present in 5.3%. Biliary stent implantation was performed in 166 patients, 59.2% of them received metal stents. Primary tumor resection was performed in 60 (16.9%) patients. Enteral or biliary bypass was done in 35 and 49 patients, respectively. In a multivariate Cox-regression model, smoking status and presence of gemcitabine-based chemotherapy were identified as independent predictors for overall survival. CONCLUSION We report the first data from a large cohort of Hungarian pancreatic cancer patients. We identified smoking status and chemotherapy as independent predictors in this cohort.

Autoimmun pancreatitis. A Magyar Hasnyálmirigy Munkacsoport bizonyítékon alapuló kezelési irányelvei

Az autoimmun pancreatitis ritka megbetegedes, amely megjeleneseben akar hasnyalmirigy-daganatot utanozhat, azonban ez utobbival ellentetben nem műteti, hanem gyogyszeres kezelest igenyel. A betegseg korrekt diagnozisa, differencialdiagnosztikaja es a betegek megfelelő kezelese korszerű es bizonyitekokon alapulo kezelesi utmutatot igenyel. A Magyar Hasnyalmirigy Munkacsoport celul tűzte ki, hogy a jelenleg elerhető nemzetkozi iranyvonalakat, illetve evidenciakat alapul veve az autoimmun pancreatitis kezelesenek kulcskerdesei vonatkozasaban bizonyitekalapu 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 4 temakorben (Alapok, Diagnozis, Differencialdiagnosztika, Terapia) 29 relevans kerdest allitott ossze. Az evidencia osztalyozasat az UpToDate ® rendszere alapjan hatarozta meg. Az osszeallitott iranyelvek a 2014. szeptember 12-ei konszenzustalalkozon kerultek bemutatasra es megvitatasra. A resztvevők minden kerdest csaknem teljes (95% feletti) egyetertessel fogadtak el. A Magyar Hasnyalmirigy Munkacsoport kezelesi iranyelvei az első, bizonyitek alapjan keszult autoimmun pancreatitis kezelesi utmutato hazankban. Az iranyelv komoly segitseget nyujthat az autoimmun pancreatitis 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), 292–307.

Open Treatment of Abdominal Wall Hernias: Mesh Repair is Superior toSuture Repair and Onlay Mesh is Better than Sublay Mesh Five-YearMulticentric, Prospective, Randomised Clinical Trial

Background: The aim of study was to compare the results of different surgical modalities/mesh (onlay/sublay position) and suture repair in treatment of abdominal hernias. Methods: According to the size of hernia gate patients were divided into two groups: small hernias (hernia gate between 5-25 cm2) and large hernias (gate > 25 cm2). In these two groups patients were randomized according to the surgical procedure: in group ‘A’ suture vs. mesh repair and in group ‘B’ onlay vs. sublay mesh reconstruction. Results: n = 734. In small hernia group significantly higher recurrences occurred after suture repair than in mesh repair (27.2% vs. 8.3% – p < 0.001). In large hernia group onlay mesh reconstruction showed significantly better results than sublay mesh repair, recurrence rate was much lower in onlay group (12.2% vs. 20.1% – p = 0.038). Wound infection presence was more significant (p=0.029) in onlay group. Conclusion: Among small hernias mesh repair provides better results than suture repair. In case of large hernia group the onlay mesh repair is significantly superior to the sublay repair, but the infection rate is much higher with only one.

Ganglioneuroma in the papilla of Vater with neurofibromatosis type 1: report of a case.

Ganglioneuromas (GNs) are rare benign tumors and their association with neurofibromatosis type 1 (NF-1) is especially uncommon. We report in this article the case of a young woman, subjected to diagnostic work-up because of abdominal pain. Endoscopy and histology revealed not only a GN in the papilla of Vater, but also NF-1. Because of the size and macroscopic features of the lesion, we performed pancreatoduodenectomy, from which she recovered uneventfully. Histological examination of the resected tumor confirmed a diagnosis of GN.

High versus low energy administration in the early phase of acute pancreatitis (GOULASH trial): protocol of a multicentre randomised double-blind clinical trial

Introduction Acute pancreatitis (AP) is an inflammatory disease with no specific treatment. Mitochondrial injury followed by ATP depletion in both acinar and ductal cells is a recently discovered early event in its pathogenesis. Importantly, preclinical research has shown that intracellular ATP delivery restores the physiological function of the cells and protects from cell injury, suggesting that restoration of energy levels in the pancreas is therapeutically beneficial. Despite several high quality experimental observations in this area, no randomised trials have been conducted to date to address the requirements for energy intake in the early phase of AP. Methods/design This is a randomised controlled two-arm double-blind multicentre trial. Patients with AP will be randomly assigned to groups A (30 kcal/kg/day energy administration starting within 24 hours of hospital admission) or B (low energy administration during the first 72 hours of hospital admission). Energy will be delivered by nasoenteric tube feeding with additional intravenous glucose supplementation or total parenteral nutrition if necessary. A combination of multiorgan failure for more than 48 hours and mortality is defined as the primary endpoint, whereas several secondary endpoints such as length of hospitalisation or pain will be determined to elucidate more detailed differences between the groups. The general feasibility, safety and quality checks required for high quality evidence will be adhered to. Ethics and dissemination The study has been approved by the relevant organisation, the Scientific and Research Ethics Committee of the Hungarian Medical Research Council (55961-2/2016/EKU). This study will provide evidence as to whether early high energy nutritional support is beneficial in the clinical management of AP. The results of this trial will be published in an open access way and disseminated among medical doctors. Trial registration The trial has been registered at the ISRCTN (ISRTCN 63827758).

[Pancreatojejunostomy--with purse-string suture].

INTRODUCTION Pancreatic fistula is one of the most relevant complications following pancreatoduodenectomies. Significant effort has been made to decrease it. The aim of the authors was to show a pancreatojejunal anastomosis combined with purse-string suture, and report the first experiences, as well. MATERIAL AND METHODS The implantation pancreatojejunostomy - which has been applied by the authors since 2003 - was modified, that the remnant of the pancreas was fixed in the jejunum with one purse-string and two mattress sutures. In case of a soft pancreas the Wirsungian duct was stented, then the vein canule was pulled out to the outside throught the afferent jejunal limb. The method was applied in seven patients during pylorus-preserving pancreatoduodenectomy performed for neoplasm. RESULTS In the postoperative period there were two complications in two patients noted (a bleeding ulcer developed in the region of the duodenojejunostomy and a transient confusion). However there was no pancreatic fistula, reoperation or early mortality detected. CONCLUSIONS While major conclusions can not be drawn due to the relatively small number of cases, this method seems promising and it is worth to carry out further trials.