Publications by authors named "Istvan Hritz"

49 Publications

Curriculum for ERCP and endoscopic ultrasound training in Europe: European Society of Gastrointestinal Endoscopy (ESGE) Position Statement.

Endoscopy 2021 Jul 26. Epub 2021 Jul 26.

Department of Gastroenterology and Hepatology, University Hospitals Leuven, and TARGID, KU Leuven, Leuven, Belgium.

The European Society of Gastrointestinal Endoscopy (ESGE) has recognized the need to formalize and enhance training in endoscopic retrograde cholangiopancreatography (ERCP) and endoscopic ultrasound (EUS). This manuscript represents the outcome of a formal Delphi process resulting in an official Position Statement of the ESGE and provides a framework to develop and maintain skills in ERCP and EUS. This curriculum is set out in terms of the prerequisites prior to training; recommended steps of training to a defined syllabus; the quality of training; and how competence should be defined and evidenced before independent practice. 1: Trainees should be competent in gastroscopy prior to commencing training. Formal training courses and the use of simulation in training are recommended. 2: Trainees should keep a contemporaneous logbook of their procedures, including key performance indicators and the degree of independence. Structured formative assessment is encouraged to enhance feedback. There should be a summative assessment process prior to commencing independent practice to ensure there is robust evidence of competence. This evidence should include a review of a trainee's procedure volume and current performance measures. A period of mentoring is strongly recommended in the early stages of independent practice. 3: Specifically for ERCP, all trainees should be competent up to Schutz level 2 complexity (management of distal biliary strictures and stones > 10 mm), with advanced ERCP requiring a further period of training. Prior to independent practice, ESGE recommends that a trainee can evidence a procedure volume of > 300 cases, a native papilla cannulation rate of ≥ 80 % (90 % after a period of mentored independent practice), complete stones clearance of ≥ 85 %, and successful stenting of distal biliary strictures of ≥ 90 % (90 % and 95 % respectively after a mentored period of independent practice). 4: The progression of EUS training and competence attainment should start from diagnostic EUS and then proceed to basic therapeutic EUS, and finally to advanced therapeutic EUS. Before independent practice, ESGE recommends that a trainee can evidence a procedure volume of > 250 cases (75 fine-needle aspirations/biopsies [FNA/FNBs]), satisfactory visualization of key anatomical landmarks in ≥ 90 % of cases, and an FNA/FNB accuracy rate of ≥ 85 %. ESGE recognizes the often inadequate quality of the evidence and the need for further studies pertaining to training in advanced endoscopy, particularly in relation to therapeutic EUS.
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http://dx.doi.org/10.1055/a-1537-8999DOI Listing
July 2021

Efficacy of Clarithromycin Depends on the Bacterial Density in Clarithromycin-Heteroresistant Infections: An Detected Susceptibility and Quantitative Morphometry-Based Retrospective Study.

Pathol Oncol Res 2021 29;27:1609863. Epub 2021 Jun 29.

2nd Department of Pathology, Semmelweis University, Budapest, Hungary.

The global rise in clarithromycin (Cla) resistance is considered to be the main contributor of () eradication failures. In nearly half of the Cla-resistant infections, Cla-susceptible bacteria are simultaneously present with the Cla-resistant ones (Cla-heteroresistance). The proportion of resistant bacteria in the bacterial population (R-fraction) and its predictive role for the use of Cla-based therapies in Cla-heteroresistant infections has not yet been investigated. Our retrospective study analyzed gastric biopsy samples of 62 -positive patients with Cla-heteroresistant infection. Fluorescence Hybridization technique was used to visualize the coexistence of resistant and susceptible bacteria within one tissue sample. R-fraction was quantified on multichannel microimages by digital morphometry. Resistant bacteria had a patchy distribution within the whole bacterial population causing high diversity among the investigated areas. Patients were subdivided into two major groups according to whether a Cla-based eradication attempt was conducted before or after the biopsy sampling. R-fraction was significantly lower among cases having only one previous Cla-based eradication attempt vs. those that had multiple previous eradications, including at least one Cla-containing therapy (0.41 vs. 0.89, = 0.0308). Majority of the patients without previous eradication attempt had successful eradication with Cla-containing regimen (59.26%), verified by a negative C-urea breath test or control biopsy. Multivariable model indicated that the therapeutic outcome using Cla-based regimens depended on the bacterial density rather than the R-fraction. Our study raises the potential use of Cla-containing eradication therapies in certain Cla-heteroresistant infections, taking into account the possible predictive role of bacterial density.
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http://dx.doi.org/10.3389/pore.2021.1609863DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8275651PMC
June 2021

Network meta-analysis of prophylactic pancreatic stents and non-steroidal anti-inflammatory drugs in the prevention of moderate-to-severe post-ERCP pancreatitis.

Pancreatology 2021 Jun 21;21(4):704-713. Epub 2021 Apr 21.

Department of Gastroenterology, BKM Hospital, Kecskemét, Hungary; Endo-kapszula Private Medical Center, Székesfehérvár, Hungary.

Background: There is an ongoing debate that non-steroidal anti-inflammatory drugs (NSAID) or prophylactic pancreatic stents (PPS) are more beneficial in preventing post-endoscopic retrograde cholangiopancreatography (ERCP) pancreatitis (PEP). In our present network meta-analysis, we aimed to compare PPSs to rectal NSAIDs in the prevention of moderate and severe PEP in average- and high-risk patients.

Methods: We performed a systematic search for randomized controlled trials (RCT) from MEDLINE (via PubMed), Embase and Cochrane Central databases. RCTs using prophylactic rectal NSAIDs or PPSs in patients subjected to ERCP at average- and high-risk population were included. The main outcome was moderate and severe PEP defined by the Cotton criteria. Pairwise Bayesian network meta-analysis was performed, and interventions were ranked based on surface under cumulative ranking (SUCRA) values.

Results: Seven NSAID RCTs (2593 patients), and 2 PPS RCTs (265 patients) in the average-risk, while 5 NSAID RCTs (1703 patients), and 8 PPS RCTs (974 patients) in the high-risk group were included in the final analysis. Compared to placebo, only PPS placement reduced the risk of moderate and severe PEP in both patient groups (average-risk: RR = 0.07, 95% CI [0.002-0.58], high-risk: RR = 0.20, 95% CI [0.051-0.56]) significantly. Rectal NSAID also reduced the risk, but this effect was not significant (average-risk: RR = 0.58, 95% CI [0.22-1.3], high-risk: RR = 0.58, 95% CI [0.18-2.3]). Based on SUCRA, PPS placement was ranked as the best preventive method.

Conclusion: Prophylactic pancreatic stent placement but not rectal NSAID seems to prevent moderate-to-severe PEP better both, in average- and high-risk patients.
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http://dx.doi.org/10.1016/j.pan.2021.04.006DOI Listing
June 2021

Prophylactic stents in the prevention of pancreatitis following endoscopic retrograde cholangiopancreatography

Orv Hetil 2021 01 3;162(1):31-38. Epub 2021 Jan 3.

3 Endo-Kapszula Magánorvosi Centrum, Székesfehérvár.

Összefoglaló. Bevezetés: Az endoszkópos retrográd cholangiopancreatographiát (ERCP) követő pancreatitis (PEP) incidenciája a magas kockázatú betegcsoportban 14,7%. Célkitűzés: A munkacsoportunk által szerzett tapasztalatok elemzése. Módszerek: A profilaktikus pancreassztentes (PPS), magas kockázatú betegek adatait tartalmazó prospektív adatbázisunkat elemeztük retrospektív módon. Az adatokat a PEP-incidencia és a súlyosság tekintetében összehasonlítottuk a korábbi, hasonlóan magas kockázatú, sztent nélküli beteganyagunkkal, illetve a sztenteléssel kapcsolatos szövődményeket és a különböző sztenttípusokat is elemeztük. A Cotton-kritériumok szerint értékeltük a PEP-t. Eredmények: A 317, magas kockázatú betegből 288 esetben (90,9%) volt sikeres a PPS-implantáció. A sztent nélküli kontrollcsoportba 121, magas kockázatú beteget választottunk be. A sikeresen sztentelt betegekben a PEP incidenciája 10,0% volt. Ez és a PEP súlyossága (enyhe: 8,3%, középsúlyos: 1,4%, súlyos: 0,3%) is szignifikánsan alacsonyabb volt a PPS nélküli beteganyaghoz (PEP: 31,4%, enyhe: 15,7%, középsúlyos: 10,7%, súlyos: 5,0%) és a sikertelenül sztentelt betegekhez (PEP: 41,3%, enyhe: 24,1%, középsúlyos: 13,8%, súlyos: 3,4%) képest. Az utóbbi két csoport közötti különbség nem volt szignifikáns. A sztenttel kapcsolatos szövődmények közül a leggyakrabban a korai sztentkicsúszást (5/288 beteg, 1,74%) és a proximalis sztentmigrációt (3/288 beteg, 1,04%) észleltük. A sztenttípusok közül a legkedvezőbb mellékhatás-profilúnak a Freeman-típusú, belső füllel és külső "pigtail" véggel ellátott sztenteket találtuk. Következtetés: A profilaktikus pancreassztentelés hatékonyan csökkenti a PEP incidenciáját, és a súlyosságát az enyhébb esetek felé tolja el. Alkalmazása viszonylag egyszerű, azonban ismerni kell használatának megfelelő technikáját, időben történő eltávolításának és a szövődmények felismerésének fontosságát. Eredményeink és a nemzetközi ajánlások alapján magas PEP-rizikójú betegekben a PPS rutinszerű alkalmazása minden ERCP-laborban ajánlott. Orv Hetil. 2021; 162(1): 31-38.

Summary:

Introduction: The most frequent complication of endoscopic retrograde cholangiopancreatography (ERCP) is post-ERCP pancreatitis (PEP). Its incidence in the high-risk patient population is 14.7%.

Objective: To analyze 10 years experiences of our working group.

Methods: We retrospectively analyzed our prospective database of high-risk patients treated with prophylactic pancreatic stents (PPS) including the period between 2009 and 2014. We compared PEP incidence and severity findings with our historical data of pre-PPS period of similarly high-risk patients (no-stent group), furthermore analyzed the complications of PPS insertion and different stent types. PEP was defined and categorized according to the Cotton criteria.

Results: In 317 high-risk patients, PPS implantation was successful in 288 cases (90.9%). The no-stent group comprised of 121 patients. Incidence and the severity of PEP in the successfully stented group (all: 10.0%; mild: 8.3%, moderate: 1.4%, severe: 0.3%) were significantly lower compared to the no-stent group (all: 31.4%; mild: 15.7%, moderate: 10.7%, severe: 5.0%) and the unsuccessfully stented group (all: 41.3%; mild: 24.1%, moderate: 13.8%, severe: 3.4%). The difference between the latter two groups was not significant. Only early dislodgment (5/288 patients, 1.74%) and proximal migration (3/288 patients, 1.04%) were observed as stent-related complications. Freeman type (single inner flange, outer pigtail end) stent was the best based on the complication profile.

Conclusion: Prophylactic pancreatic stenting effectively lowers the incidence and severity of PEP. We should recognize the proper technic of its application and the importance of proper timing of its extraction and identification of complications. Utilization of PPSs in high-risk patients is strongly recommended in every ERCP center. Orv Hetil. 2021; 162(1): 31-38.
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http://dx.doi.org/10.1556/650.2021.31934DOI Listing
January 2021

Az endoszkópia és gasztroenterológia szerepe, múltja, jelene és jövője a Semmelweis Egyetem I. sz. Sebészeti Klinikáján.

Magy Seb 2020 Sep;73(3):110-111

I. sz. Sebészeti Klinika, Semmelweis Egyetem, Budapest.

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http://dx.doi.org/10.1556/1046.73.2020.3.9DOI Listing
September 2020

The Behavior of MMP-2, MMP-7, MMP-9, and Their Inhibitors TIMP-1 and TIMP-2 in Adenoma-Colorectal Cancer Sequence.

Dig Dis 2021 22;39(3):217-224. Epub 2020 Sep 22.

Department of Gastroenterology, Hungarian Defence Forces, Budapest, Hungary,

Background: We and others have previously shown that matrix metalloproteinases (MMPs) play a role in colorectal cancer (CRC) invasion and metastasis. However, the serum changes of various MMPs and their inhibitors (TIMPs) have scarcely been concomitantly investigated in identical blood samples in the normal colon-adenoma-CRC sequence.

Methods: The MMP-2, MMP-7, MMP-9, TIMP-1, and TIMP-2 serum antigen concentrations were determined concomitantly in 19 tumor-free control patients, 19 patients with high-risk colorectal adenoma, and 47 patients with CRC by ELISA technique. The analyzed parameters were also investigated in correlation with CRC stages. Statistical analysis with one-way ANOVA and Student's t test was performed. p values <0.05 were considered significant.

Results: Serum antigen levels of MMPs and TIMPs were significantly increased in patients with CRC and adenomas compared to controls (mean values, ng/mL) (MMP-7: 5.88, 4.44, and 2.89, respectively, p = 0.001; MMP-9: 1,075.81, 999.22, and 845.97, respectively, p = 0.01; TIMP-1: 241.80, 205.98, and 166.53, respectively, p = 0.001; TIMP-2: 83.40, 80.30, and 69.62, respectively, p = 0.01). The elevated serum MMP-7, MMP-9, TIMP-1, and TIMP-2 levels significantly correlated with advanced tumor stages (p < 0.05). No statistically significant differences were observed in MMP-2 levels.

Conclusions: We demonstrate that serum antigen concentrations of MMP-7, MMP-9, TIMP-1, and TIMP-2 were significantly increased in patients with CRC and adenomas compared to controls. These results suggest that MMPs and their inhibitors TIMP-1 and TIMP-2 play an important role in CRC invasion; however, they are also activated in premalignant adenomas. Furthermore, MMP-7, MMP-9, TIMP-1, and TIMP-2 may have a potential prognostic impact in CRC.
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http://dx.doi.org/10.1159/000511765DOI Listing
May 2021

Cholecystectomia során bekövetkező epeútsérülések ellátása.

Magy Seb 2020 Jun;73(2):49-56

I. sz. Sebészeti Klinika,Semmelweis Egyetem Budapest.

Biliary injury is a rare but a very serious complication of laparoscopic cholecystectomy (LC). Our aim was to analyse the incidence of the biliary injuries and its therapeutic outcome on patients who underwent LC or converted LC. Our research was conducted at the 1st Department of Surgery, Semmelweis University, Budapest between 2006 and 2016, retrospectively. We analysed the LCs and converted LCs performed at our Department and as well as cases where the primary operations were conducted at other institutions but they were unable to provide the adequate therapy for the injury, thus the patients were transferred to our institution. At the 1st Department of Surgery complications occurred in 0,66% (30/4885) of all LCs. 327 converted LCs were done, complications occurred in 26 (7.95%) times. 22 patients were transferred to the 1st Department of Surgery from other institutions. Bilio-vascular injuries occurred in 61% (41/78). ERCP was performed in 25 cases with a 92% success rate. Reoperation was needed in 41% (28/41). Biliary reconstruction during the reoperation was performed via hepaticojejunostomy in 82% of all reoperations. The therapeutic solutions of LC's complications are complex. Therefore, the treatment is recommended only in institutions with appropriate experience.
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http://dx.doi.org/10.1556/1046.73.2020.2.1DOI Listing
June 2020

ERCP-related adverse events: European Society of Gastrointestinal Endoscopy (ESGE) Guideline.

Endoscopy 2020 02 20;52(2):127-149. Epub 2019 Dec 20.

Department of Gastroenterology and Hepatology, Amsterdam University Medical Centers, University of Amsterdam, The Netherlands.

Prophylaxis: 1:  ESGE recommends routine rectal administration of 100 mg of diclofenac or indomethacin immediately before endoscopic retrograde cholangiopancreatography (ERCP) in all patients without contraindications to nonsteroidal anti-inflammatory drug administration.Strong recommendation, moderate quality evidence. 2:  ESGE recommends prophylactic pancreatic stenting in selected patients at high risk for post-ERCP pancreatitis (inadvertent guidewire insertion/opacification of the pancreatic duct, double-guidewire cannulation).Strong recommendation, moderate quality evidence. 3:  ESGE suggests against routine endoscopic biliary sphincterotomy before the insertion of a single plastic stent or an uncovered/partially covered self-expandable metal stent for relief of biliary obstruction.Weak recommendation, moderate quality evidence. 4:  ESGE recommends against the routine use of antibiotic prophylaxis before ERCP.Strong recommendation, moderate quality evidence. 5:  ESGE suggests antibiotic prophylaxis before ERCP in the case of anticipated incomplete biliary drainage, for severely immunocompromised patients, and when performing cholangioscopy.Weak recommendation, moderate quality evidence. 6:  ESGE suggests tests of coagulation are not routinely required prior to ERCP for patients who are not on anticoagulants and not jaundiced.Weak recommendation, low quality evidence.

Treatment: 7:  ESGE suggests against salvage pancreatic stenting in patients with post-ERCP pancreatitis.Weak recommendation, low quality evidence. 8:  ESGE suggests temporary placement of a biliary fully covered self-expandable metal stent for post-sphincterotomy bleeding refractory to standard hemostatic modalities.Weak recommendation, low quality evidence. 9:  ESGE suggests to evaluate patients with post-ERCP cholangitis by abdominal ultrasonography or computed tomography (CT) scan and, in the absence of improvement with conservative therapy, to consider repeat ERCP. A bile sample should be collected for microbiological examination during repeat ERCP.Weak recommendation, low quality evidence.
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http://dx.doi.org/10.1055/a-1075-4080DOI Listing
February 2020

Risk factors of post-ERCP pancreatitis in high-risk patients despite prevention with prophylactic pancreatic stents.

Scand J Gastroenterol 2020 Jan 18;55(1):95-99. Epub 2019 Dec 18.

Department of Gastroenterology, Bács-Kiskun Megyei Kórház, Kecskemét, Hungary.

To analyze risk factors of post-ERCP pancreatitis (PEP) in high risk patients in whom prophylactic pancreatic stents (PPSs) were intended to use to prevent endoscopic retrograde cholangiography (ERCP)-related complications. Three hundred and seventeen high-risk patients for developing PEP were considered for preventive pancreatic stent placement in our endoscopy unit over 5 years. 5 Fr, 3-5 cm long PPSs were used. All data were collected in a predefined database. Development of PEP despite PPS placement was analyzed. PEP occurred in 29 of 288 successfully stented patients (10.07%; 24 mild, four moderate, one severe). PPS was protective against all risks factors except for sphincter of Oddi dysfunction (SOD). PPS related complication rate was 2.78% ( = 8). Unsuccessful stenting occurred in 29 patients (9.15%), PEP developed in 41.38% ( = 12; seven mild, four moderate, one severe). Those patients who had more patient related risk factors were more likely to develop PEP despite preventive measures with PPS. On the contrary, PPS placement was less successful in patients who had more procedure related risk factors. PPS is protective against all risks factors of PEP except for SOD in high-risk patients. More vulnerable patients who have more patient-related risk factors are more likely to develop PEP despite PPS is used, while more complex procedures predispose to unsuccessful PPS placement in patients with more procedure-related risk factors. PPS insertion in high-risk patients is effective and safe preventive method and the procedure related complication rate is reasonably low.
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http://dx.doi.org/10.1080/00365521.2019.1701069DOI Listing
January 2020

Helicobacter pylori heteroresistance to clarithromycin in adults-New data by in situ detection and improved concept.

Helicobacter 2020 Feb 8;25(1):e12670. Epub 2019 Nov 8.

Second Department of Pathology, Semmelweis University, Budapest, Hungary.

Background: Clarithromycin (Cla) heteroresistance of Helicobacter pylori (H pylori) infections is commonly assessed by comparing the resistance status of antrum and corpus biopsy samples and by demonstrating the discrepancy between them (interniche heteroresistance). However, fluorescence in situ hybridization (FISH) technique is capable of showing the synchronous presence of susceptible and resistant bacteria (intraniche heteroresistance), enabling the detection of heteroresistant H pylori populations within one biopsy sample.

Materials And Methods: Antrum and corpus biopsy specimens of 305 H pylori-infected patients were investigated with an rRNA-targeted Cla-resistance FISH test. Anamnestic data were collected from the institutional electronic register. Prevalence rates of susceptible, homo- and heteroresistant cases were correlated with the anamnestic and clinicopathological data.

Results: Overall Cla-resistance rate was 23.9% (73 cases), consisting of 35 (11.5%) homoresistant and 38 (12.5%) heteroresistant cases. Thirty-five patients had at least one biopsy site where susceptible and resistant bacteria were present simultaneously. From this subset, 20 cases demonstrated intraniche heteroresistance on both sites. Prior Cla-based eradication attempts were more frequent in homoresistant than in susceptible and heteroresistant cases (P < .001, P < .001, respectively). Cla-containing therapy eradicated heteroresistant infections at a significantly lower rate in comparison with susceptible cases (P = .0112), but more effectively than homoresistants (P = .0393).

Conclusions: The most frequent type of Cla-heteroresistance is the coexistence of susceptible and resistant H pylori bacteria in the same location (intraniche heteroresistance). A previous Cla-based eradication attempt predisposes patients to homoresistant infection. Heteroresistance is characterized by a non-eradication-related background and intermediate characteristics in many respects when compared to susceptible and homoresistant cases.
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http://dx.doi.org/10.1111/hel.12670DOI Listing
February 2020

Outcomes and timing of endoscopic retrograde cholangiopancreatography for acute biliary pancreatitis.

Dig Liver Dis 2019 09 25;51(9):1281-1286. Epub 2019 Apr 25.

Institute for Translational Medicine, Medical School, University of Pécs, Pécs, Hungary. Electronic address:

Background: Indication of endoscopic retrograde cholangiopancreatography (ERCP) in acute biliary pancreatitis (ABP) is challenging.

Aims: In this retrospective study, we analyzed real-world data to understand the ERCP practice in ABP in Hungarian centers.

Methods: Clinical data on ABP patients (2013-2015) were extracted from our large multicentric database. Outcomes, quality indicators and the role of early timing of ERCP (<24 h from admission) were analyzed.

Results: There were 356 patients with ABP. ERCP was performed in 267 (75%). Performance indicators of ERCP proved to be suboptimal with a biliary cannulation rate of 84%. Successful vs unsuccessful cannulation of naïve papilla resulted in lower rates of local [22.9% vs 40.9%, (P = 0.012)] and systemic [4.9% vs 13.6%, (P = 0.042)] complications. Successful vs unsuccessful clearance resulted in lower rates of local complications [22.5% vs 40.8%, (P = 0.008)]. Successful cannulation and drainage correlated with less severe course of ABP [3.6% vs 15.9%, (P = 0.001) and 4.1% vs 12.2%, (P = 0.033)] respectively. A tendency of an increased rate of local complications was observed if ERCP was performed later [<24 h: 21.1% (35/166); between 24-48 h: 23.4% (11/47); >48h: 37.2% (16/43) (P = 0.088)].

Conclusion: Optimization of ERCP indication in ABP patients is critical as suboptimal ERCP practices in ABP without definitive stone detection are associated with poorer clinical outcomes.
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http://dx.doi.org/10.1016/j.dld.2019.03.018DOI Listing
September 2019

Endoscopic management of common bile duct stones: European Society of Gastrointestinal Endoscopy (ESGE) guideline.

Endoscopy 2019 05 3;51(5):472-491. Epub 2019 Apr 3.

Department of Gastroenterology and Hepatology, Amsterdam University Medical Center, University of Amsterdam, Amsterdam, The Netherlands.

ESGE recommends offering stone extraction to all patients with common bile duct stones, symptomatic or not, who are fit enough to tolerate the intervention.Strong recommendation, low quality evidence.ESGE recommends liver function tests and abdominal ultrasonography as the initial diagnostic steps for suspected common bile duct stones. Combining these tests defines the probability of having common bile duct stones.Strong recommendation, moderate quality evidence.ESGE recommends endoscopic ultrasonography or magnetic resonance cholangiopancreatography to diagnose common bile duct stones in patients with persistent clinical suspicion but insufficient evidence of stones on abdominal ultrasonography.Strong recommendation, moderate quality evidence.ESGE recommends the following timing for biliary drainage, preferably endoscopic, in patients with acute cholangitis, classified according to the 2018 revision of the Tokyo Guidelines:- severe, as soon as possible and within 12 hours for patients with septic shock- moderate, within 48 - 72 hours- mild, elective.Strong recommendation, low quality evidence.ESGE recommends endoscopic placement of a temporary biliary plastic stent in patients with irretrievable biliary stones that warrant biliary drainage.Strong recommendation, moderate quality of evidence.ESGE recommends limited sphincterotomy combined with endoscopic papillary large-balloon dilation as the first-line approach to remove difficult common bile duct stones. Strong recommendation, high quality evidence.ESGE recommends the use of cholangioscopy-assisted intraluminal lithotripsy (electrohydraulic or laser) as an effective and safe treatment of difficult bile duct stones.Strong recommendation, moderate quality evidence.ESGE recommends performing a laparoscopic cholecystectomy within 2 weeks from ERCP for patients treated for choledocholithiasis to reduce the conversion rate and the risk of recurrent biliary events. Strong recommendation, moderate quality evidence.
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http://dx.doi.org/10.1055/a-0862-0346DOI Listing
May 2019

Endoscopic management of acute necrotizing pancreatitis: European Society of Gastrointestinal Endoscopy (ESGE) evidence-based multidisciplinary guidelines.

Endoscopy 2018 05 9;50(5):524-546. Epub 2018 Apr 9.

Department of Gastroenterology and Hepatology, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.

1:  ESGE suggests using contrast-enhanced computed tomography (CT) as the first-line imaging modality on admission when indicated and up to the 4th week from onset in the absence of contraindications. Magnetic resonance imaging (MRI) may be used instead of CT in patients with contraindications to contrast-enhanced CT, and after the 4th week from onset when invasive intervention is considered because the contents (liquid vs. solid) of pancreatic collections are better characterized by MRI and evaluation of pancreatic duct integrity is possible. Weak recommendation, low quality evidence. 2:  ESGE recommends against routine percutaneous fine needle aspiration (FNA) of (peri)pancreatic collections. Strong recommendation, moderate quality evidence. FNA should be performed only if there is suspicion of infection and clinical/imaging signs are unclear. Weak recommendation, low quality evidence. 3:  ESGE recommends initial goal-directed intravenous fluid therapy with Ringer's lactate (e. g. 5 - 10 mL/kg/h) at onset. Fluid requirements should be patient-tailored and reassessed at frequent intervals. Strong recommendation, moderate quality evidence. 4:  ESGE recommends against antibiotic or probiotic prophylaxis of infectious complications in acute necrotizing pancreatitis. Strong recommendation, high quality evidence. 5:  ESGE recommends invasive intervention for patients with acute necrotizing pancreatitis and clinically suspected or proven infected necrosis. Strong recommendation, low quality evidence.ESGE suggests that the first intervention for infected necrosis should be delayed for 4 weeks if tolerated by the patient. Weak recommendation, low quality evidence. 6:  ESGE recommends performing endoscopic or percutaneous drainage of (suspected) infected walled-off necrosis as the first interventional method, taking into account the location of the walled-off necrosis and local expertise. Strong recommendation, moderate quality evidence. 7:  ESGE suggests that, in the absence of improvement following endoscopic transmural drainage of walled-off necrosis, endoscopic necrosectomy or minimally invasive surgery (if percutaneous drainage has already been performed) is to be preferred over open surgery as the next therapeutic step, taking into account the location of the walled-off necrosis and local expertise. Weak recommendation, low quality evidence. 8:  ESGE recommends long-term indwelling of transluminal plastic stents in patients with disconnected pancreatic duct syndrome. Strong recommendation, low quality evidence. Lumen-apposing metal stents should be retrieved within 4 weeks to avoid stent-related adverse effects.Strong recommendation, low quality evidence.
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http://dx.doi.org/10.1055/a-0588-5365DOI Listing
May 2018

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

PLoS One 2016 31;11(10):e0165309. Epub 2016 Oct 31.

Bajcsy-Zsilinszky Hospital, Budapest, Hungary.

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.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0165309PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5087847PMC
June 2017

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

Pancreas 2016 Apr;45(4):541-5

From the *First Department of Medicine, University of Szeged, Szeged, Hungary; †Department of Molecular and Cell Biology, Boston University Henry M. Goldman School of Dental Medicine, Boston, MA; ‡Department of Pharmacology and Pharmacotherapy, Faculty of Medicine, University of Szeged, Szeged, Hungary; §2nd Department of Pediatrics, Comenius University Medical School, University Children's Hospital, Bratislava, Slovakia; ∥First Department of Internal Medicine, University of Pécs, Hungary; ¶Institute of Surgery, University of Debrecen, Clinical Center, Debrecen, Hungary; #Heim Pál Children's Hospital, Budapest, Hungary; **First Department of Medicine, Szent György Teaching Hospital of County Fejér, Székesfehérvár, Hungary; ††Department of Oncotherapy, University of Szeged, Szeged, Hungary; and ‡‡MTA-SZTE Translational Gastroenterology Research Group, Szeged, Hungary.

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.
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http://dx.doi.org/10.1097/MPA.0000000000000539DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4783207PMC
April 2016

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

Pancreatology 2015 Sep-Oct;15(5):508-513. Epub 2015 Sep 1.

Institute of Surgery, University of Debrecen, Clinical Center, Debrecen Hungary.

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.
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http://dx.doi.org/10.1016/j.pan.2015.08.008DOI Listing
July 2016

SPINK1 Promoter Variants in Chronic Pancreatitis.

Pancreas 2016 Jan;45(1):148-53

From the *First Department of Medicine, University of Szeged, Szeged, Hungary; †Second Department of Pediatrics, Comenius University Medical School, University Children's Hospital, Bratislava, Slovakia; ‡Department of Molecular and Cell Biology, Boston University Henry M. Goldman School of Dental Medicine, Boston, MA; §First Department of Medicine, Szent György Teaching Hospital of County Fejér, Székesfehérvár; ∥Heim Pál Children's Hospital, Budapest; ¶Department of Surgery and #First Department of Internal Medicine, University of Pécs, Pécs; and **MTA-SZTE Translational Gastroenterology Research Group, Szeged, Hungary.

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.
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http://dx.doi.org/10.1097/MPA.0000000000000412DOI Listing
January 2016

Early Achievable Severity (EASY) index for simple and accurate expedite risk stratification in acute pancreatitis.

J Gastrointestin Liver Dis 2015 Jun;24(2):177-82

1st Department of Medicine, University of Szeged; MTA-SZTE Lendület Translational Gastroenterology Research Group, Szeged, Hungary.

Background: Acute pancreatitis (AP) is one of the most common diseases of the gastrointestinal tract associated with significant morbidity and mortality. The assessment of severity is crucial in the management of the disease. Current methods of risk stratification in AP have a limited value, as they provide little additional information thus delaying appropriate patient care. Early recognition of severe disease may prevent serious adverse events and improve patient management as well as overall clinical outcome.

Methods/design: The EASY trial is an observational, multicenter, prospective cohort study for establishing a simple, easy and accurate clinical scoring system for early prognostication of AP. Evaluation of simple attainable potential prognostic parameters obtained at admission (or not later than 6-12 hours afterwards) from patients diagnosed with AP will be performed to assess their potential correlation with the disease severity. The selected parameters that show the strongest correlation with severe disease course will be further utilized as potential early severity prognostic markers for prospective new patient stratification. Comparison of patients' clinical course with the obtained results of early risk stratification may validate the utilized parameters as prognostic markers. The trial has been (i) discussed and (ii) accepted in a distinguished international scientific meeting, (ii) receiving the relevant ethical approval (TÜKEB: 30595-1/2014/EKU), (ii) registered at the ISRCTN registry which is a primary clinical trial registry recognized by WHO (Trial registration number: ISRCTN10525246).

Conclusion: The EASY trial is designed to develop a simple and accurate clinical scoring system that can stratify patients with AP during the first 6-12 hours of hospitalization according to their risk for severe disease course.
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http://dx.doi.org/10.15403/jgld.2014.1121.242.easyDOI Listing
June 2015

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

Pancreatology 2015 Mar-Apr;15(2):115-23. Epub 2015 Feb 25.

Department of Gastroenterology and Endoscopy, Bács-Kiskun County Hospital, Nyíri út 38, 6000 Kecskemét, Hungary.

Background: The 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.

Methods/design: PREPAST 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 48 h 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 48 h 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.

Discussion: The 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).
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http://dx.doi.org/10.1016/j.pan.2015.02.007DOI Listing
December 2015

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

Orv Hetil 2015 Feb;156(8):326-39

Péterfy Sándor utcai Kórház-Rendelőintézet Budapest.

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.
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http://dx.doi.org/10.1556/OH.2015.30063DOI Listing
February 2015

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

Orv Hetil 2015 Feb;156(8):308-25

Heim Pál Gyermekkórház-Rendelőintézet Budapest.

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.
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http://dx.doi.org/10.1556/OH.2015.30062DOI Listing
February 2015

[Autoimmune pancreatitis. Evidence based management guidelines of the Hungarian Pancreatic Study Group].

Orv Hetil 2015 Feb;156(8):292-307

Szegedi Tudományegyetem, Általános Orvostudományi Kar, Szent-Györgyi Albert Klinikai Központ I. Belgyógyászati Klinika Szeged.

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.
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http://dx.doi.org/10.1556/OH.2015.30061DOI Listing
February 2015

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

Orv Hetil 2015 Feb;156(7):262-88

Semmelweis Egyetem, Általános Orvostudományi Kar I. Sebészeti Klinika Budapest.

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.
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http://dx.doi.org/10.1556/OH.2015.30060DOI Listing
February 2015

[Acute pancreatitis. Evidence-based practice guidelines, prepared by the Hungarian Pancreatic Study Group].

Orv Hetil 2015 Feb;156(7):244-61

Szegedi Tudományegyetem, Általános Orvostudományi Kar, Szent-Györgyi Albert Klinikai Központ I. Belgyógyászati Klinika Szeged MTA-SZTE Lendület Gasztroenterológiai Multidiszciplináris Kutatócsoport Szeged.

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.
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http://dx.doi.org/10.1556/OH.2015.30059DOI Listing
February 2015

Impact of proteolytic enzymes in colorectal cancer development and progression.

World J Gastroenterol 2014 Oct;20(37):13246-57

László Herszényi, Zsolt Tulassay, 2 Department of Medicine, Semmelweis University, H-1088 Budapest, Hungary.

Tumor invasion and metastasis is a highly complicated, multi-step phenomenon. In the complex event of tumor progression, tumor cells interact with basement membrane and extracellular matrix components. Proteolytic enzymes (proteinases) are involved in the degradation of extracellular matrix, but also in cancer invasion and metastasis. The four categories of proteinases (cysteine-, serine-, aspartic-, and metalloproteinases) are named and classified according to the essential catalytic component in their active site. We and others have shown that proteolytic enzymes play a major role not only in colorectal cancer (CRC) invasion and metastasis, but also in malignant transformation of precancerous lesions into cancer. Tissue and serum-plasma antigen concentrations of proteinases might be of great value in identifying patients with poor prognosis in CRC. Our results, in concordance with others indicate the potential tumor marker impact of proteinases for the early diagnosis of CRC. In addition, proteinases may also serve as potential target molecules for therapeutic agents.
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http://dx.doi.org/10.3748/wjg.v20.i37.13246DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4188883PMC
October 2014

Endoscopic transluminal pancreatic necrosectomy using a self-expanding metal stent and high-flow water-jet system.

World J Gastroenterol 2013 Jun;19(23):3685-92

Department of Gastroenterology and Endoscopy, Fejér Megyei Szent György Teaching Hospital, H-8000 Székesfehérvár, Hungary.

Walled-off pancreatic necrosis and a pancreatic abscess are the most severe complications of acute pancreatitis. Surgery in such critically ill patients is often associated with significant morbidity and mortality within the first few weeks after the onset of symptoms. Minimal invasive approaches with high success and low mortality rates are therefore of considerable interest. Endoscopic therapy has the potential to offer safe and effective alternative treatment. We report here on 3 consecutive patients with infected walled-off pancreatic necrosis and 1 patient with a pancreatic abscess who underwent direct endoscopic necrosectomy 19-21 d after the onset of acute pancreatitis. The infected pancreatic necrosis or abscess was punctured transluminally with a cystostome and, after balloon dilatation, a non-covered self-expanding biliary metal stent was placed into the necrotic cavity. Following stent deployment, a nasobiliary pigtail catheter was placed into the cavity to ensure continuous irrigation. After 5-7 d, the metal stent was removed endoscopically and the necrotic cavity was entered with a therapeutic gastroscope. Endoscopic debridement was performed via the simultaneous application of a high-flow water-jet system; using a flush knife, a Dormia basket, and hot biopsy forceps. The transluminal endotherapy was repeated 2-5 times daily during the next 10 d. Supportive care included parenteral antibiotics and jejunal feeding. All patients improved dramatically and with resolution of their septic conditions; 3 patients were completely cured without any further complications or the need for surgery. One patient died from a complication of prolonged ventilation severe bilateral pneumonia, not related to the endoscopic procedure. No procedure related complications were observed. Transluminal endoscopic necrosectomy with temporary application of a self-expanding metal stent and a high-flow water-jet system shows promise for enhancing the potential of this endoscopic approach in patients with walled-off pancreatic necrosis and/or a pancreatic abscess.
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http://dx.doi.org/10.3748/wjg.v19.i23.3685DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3691031PMC
June 2013

The behavior of matrix metalloproteinases and their inhibitors in colorectal cancer.

Int J Mol Sci 2012 Oct 16;13(10):13240-63. Epub 2012 Oct 16.

Second Department of Medicine, Semmelweis University, H-1088 Budapest, Szentkirályi str. 46, H-1088, Hungary.

Matrix metalloproteinases (MMPs) play an important role in the degradation of extracellular matrix components crucial for tumor growth, invasion and metastasis. MMPs are controlled by natural inhibitors called tissue inhibitors of metalloproteinases (TIMPs). We and others have demonstrated that MMPs and TIMPs are especially important in the process of tumor invasion, progression and the metastasis of colorectal cancer (CRC). It has been proposed that MMPs and TIMPs might play a part not only in tumor invasion and initiation of metastasis but also in carcinogenesis from colorectal adenomas. Several recent studies demonstrated that high preoperative serum or plasma MMP-2, MMP-9 and TIMP-1 antigen levels are strong predictive factors for poor prognosis in patients with CRC and their determination might be useful for identification of patients with higher risk for cancer recurrence. MMP-9 and TIMP-1 have significant potential tumor marker impact in CRC. Their diagnostic sensitivity is consistently higher than those of conventional biomarkers. The pharmacological targeting of CRC by the development of a new generation of selective inhibitors of MMPs, that is highly specific for certain MMPs, is a promising and challenging area for the future.
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http://dx.doi.org/10.3390/ijms131013240DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3497324PMC
October 2012

The impact of matrix metalloproteinases and their tissue inhibitors in inflammatory bowel diseases.

Dig Dis 2012 20;30(3):289-95. Epub 2012 Jun 20.

2nd Department of Medicine, Semmelweis University, Budapest, Hungary.

Background: It has been suggested that matrix metalloproteinases (MMPs) may play a role in the pathogenesis of inflammatory bowel diseases (IBD). However, the impact of serum MMPs and their inhibitors [tissue inhibitors of metalloproteinases (TIMPs)] have scarcely been investigated in the same experimental setting in ulcerative colitis (UC) and Crohn's disease (CD) as well as their correlation with IBD activity.

Methods: MMP-2, MMP-7, MMP-9, TIMP-1 and TIMP-2 serum antigen levels were determined in 23 patients with UC, 25 patients with CD and 10 healthy control patients by enzyme-linked immunoassay technique. Statistical analysis with one-way ANOVA and Student's t tests was performed. A linear regression analysis or a Spearman's r test was used to assess correlation. Differences were considered significant with p < 0.05.

Results: Serum antigen concentrations of MMP-9, TIMP-1 and TIMP-2 were significantly higher in UC and CD patients compared to controls. MMP-7 was also significantly higher in CD compared with controls. Elevated MMP-9 and TIMP-1 antigen levels showed significant positive correlation with disease activity of IBD. MMP-2 and TIMP-2 levels inversely correlated with CD activity. Significant correlations were found between MMP-9/TIMP-1 and MMP-2/TIMP-2 antigen levels in both UC and CD.

Conclusions: We demonstrated that serum antigen concentrations of MMP-9, TIMP-1 and TIMP-2 were significantly increased in patients with UC and CD compared to controls. Our results suggest that MMPs and TIMPs may contribute to the inflammatory and remodeling processes in IBD. Serum MMP-9 and TIMP-1 might be useful as additional biomarkers in the assessment of IBD activity.
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http://dx.doi.org/10.1159/000336995DOI Listing
November 2012

The role of inflammation and proteinases in tumor progression.

Dig Dis 2012 20;30(3):249-54. Epub 2012 Jun 20.

2nd Department of Medicine, Semmelweis University, Budapest, Hungary.

Chronic inflammation is an important risk factor for the development of cancers. The link between chronic inflammation and the risk of developing cancer is now well established. At least 20% of all cancers arise in association with infection and chronic inflammation. Inflammation and cancer are linked both along intrinsic (driven by genetic events causing malignancy) and extrinsic (driven by inflammatory conditions predisposing to tumor) pathways. Proteinases are key contributors to the breakdown and reconstitution of extracellular matrix components in physiological processes and pathological conditions, including destructive diseases and tumor progression. Matrix metalloproteinases are especially essential in the complex process of coregulation between cellular components of the tumor environment, and they are considered as potential diagnostic and prognostic biomarkers in many types and stages of cancer. Although the link between chronic inflammation, proteinases and risk of developing cancer is now well established, several open questions remain. The most exciting challenge is to find the best approach to target cancer-associated inflammation in patients with cancer. With respect to matrix metalloproteinases, the development of a new generation of selective inhibitors is a promising area of research.
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http://dx.doi.org/10.1159/000336914DOI Listing
November 2012
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