Dóra Mosztbacher

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.

Meta-analysis of the long term success rate of different interventions in benign biliary strictures

Background Benign biliary stricture is a rare condition and the majority of the cases are caused by operative trauma or chronic inflammation based on various etiology. Although the initial results of endoscopic, percutaneous and surgical treatment are impressive, no comparison about long term stricture resolution is available. Aims The goal of this study was to compare the long term disease free survival in benign biliary strictures with various etiology after surgery, percutaneous transhepatic—and endoscopic treatment. Methods PubMed, Embase, and Cochrane Library were searched by computer and manually for published studies. The investigators selected the publications according to the inclusion and exclusion criteria, processed the data and assessed the quality of the selected studies. Meta-analysis of data of 24 publications was performed to compare long term disease free survival of different treatment groups. Results Compared the subgroups surgery resulted in the highest long term stricture resolution rate, followed by the percutaneous transhepatic treatment, the multiple plastic stent insertion and covered self-expanding metal stents (SEMS), however the difference was not significant. All compared methods are significantly superior to the single plastic stent placement. Long term stricture resolution rate irrespectively of any therapy is still not more than 84%. Conclusions In summary, the use of single plastic stent is not recommended. Further randomized studies and innovative technical development are required for improving the treatment of benign biliary strictures.

Meta-analysis of early nutrition: The benefits of enteral feeding compared to a nil per os diet not only in severe, but also in mild and moderate acute pancreatitis

The recently published guidelines for acute pancreatitis (AP) suggest that enteral nutrition (EN) should be the primary therapy in patients suffering from severe acute pancreatitis (SAP); however, none of the guidelines have recommendations on mild and moderate AP (MAP). A meta-analysis was performed using the preferred reporting items for systematic review and meta-analysis protocols (PRISMA-P). The following PICO (problem, intervention, comparison, outcome) was applied: P: nutrition in AP; I: enteral nutrition (EN); C: nil per os diet (NPO); and O: outcome. There were 717 articles found in Embase, 831 in PubMed, and 10 in the Cochrane database. Altogether, seven SAP and six MAP articles were suitable for analyses. In SAP, forest plots were used to illustrate three primary endpoints (mortality, multiorgan failure, and intervention). In MAP, 14 additional secondary endpoints were analyzed (such as CRP (C-reactive protein), WCC (white cell count), complications, etc.). After pooling the data, the Mann–Whitney U test was used to detect significant differences. Funnel plots were created for testing heterogeneity. All of the primary endpoints investigated showed that EN is beneficial vs. NPO in SAP. In MAP, all of the six articles found merit in EN. Analyses of the primary endpoints did not show significant differences between the groups; however, analyzing the 17 endpoints together showed a significant difference in favor of EN vs. NPO. EN is beneficial compared to a nil per os diet not only in severe, but also in mild and moderate AP.

Analysis of research activity in gastroenterology: Pancreatitis is in real danger

Objective Biomedical investment trends in 2015 show a huge decrease of investment in gastroenterology. Since academic research usually provides the basis for industrial research and development (R&D), our aim was to understand research trends in the field of gastroenterology over the last 50 years and identify the most endangered areas. Methods We searched for PubMed hits for gastrointestinal (GI) diseases for the 1965–2015 period. Overall, 1,554,325 articles were analyzed. Since pancreatology was identified as the most endangered field of research within gastroenterology, we carried out a detailed evaluation of research activity in pancreatology. Results In 1965, among the major benign GI disorders, 51.9% of the research was performed on hepatitis, 25.7% on pancreatitis, 21.7% on upper GI diseases and only 0.7% on the lower GI disorders. Half a century later, in 2015, research on hepatitis and upper GI diseases had not changed significantly; however, studies on pancreatitis had dropped to 10.7%, while work on the lower GI disorders had risen to 23.4%. With regard to the malignant disorders (including liver, gastric, colon, pancreatic and oesophageal cancer), no such large-scale changes were observed in the last 50 years. Detailed analyses revealed that besides the drop in research activity in pancreatitis, there are serious problems with the quality of the studies as well. Only 6.8% of clinical trials on pancreatitis were registered and only 5.5% of these registered trials were multicentre and multinational (more than five centres and nations), i.e., the kind that provides the highest level of impact and evidence level. Conclusions There has been a clear drop in research activity in pancreatitis. New international networks and far more academic R&D activities should be established in order to find the first therapy specifically for acute pancreatitis.

Restoration of energy level in the early phase of acute pediatric pancreatitis

Acute pancreatitis (AP) is a serious inflammatory disease with rising incidence both in the adult and pediatric populations. It has been shown that mitochondrial injury and energy depletion are the earliest intracellular events in the early phase of AP. Moreover, it has been revealed that restoration of intracellular ATP level restores cellular functions and defends the cells from death. We have recently shown in a systematic review and meta-analysis that early enteral feeding is beneficial in adults; however, no reviews are available concerning the effect of early enteral feeding in pediatric AP. In this minireview, our aim was to systematically analyse the literature on the treatment of acute pediatric pancreatitis. The preferred reporting items for systematic review (PRISMA-P) were followed, and the question was drafted based on participants, intervention, comparison and outcomes: P: patients under the age of twenty-one suffering from acute pancreatitis; I: early enteral nutrition (per os and nasogastric- or nasojejunal tube started within 48 h); C: nil per os therapy; O: length of hospitalization, need for treatment at an intensive care unit, development of severe AP, lung injury (including lung oedema and pleural effusion), white blood cell count and pain score on admission. Altogether, 632 articles (PubMed: 131; EMBASE: 501) were found. After detailed screening of eligible papers, five of them met inclusion criteria. Only retrospective clinical trials were available. Due to insufficient information from the authors, it was only possible to address length of hospitalization as an outcome of the study. Our mini-meta-analysis showed that early enteral nutrition significantly (SD = 0.806, P = 0.034) decreases length of hospitalization compared with nil per os diet in acute pediatric pancreatitis. In this minireview, we clearly show that early enteral nutrition, started within 24-48 h, is beneficial in acute pediatric pancreatitis. Prospective studies and better presentation of research are crucially needed to achieve a higher level of evidence.

Transpancreatic sphincterotomy has a higher cannulation success rate than needle-knife precut papillotomy – a meta-analysis

Background and aim While many studies have discussed the different cannulation techniques used in patients with difficult biliary access, no previous meta-analyses have compared transpancreatic sphincterotomy (TPS) to other advanced techniques. Therefore, we aimed to identify all studies comparing the efficacy and adverse event rates of TPS with needle-knife precut papillotomy (NKPP), the most commonly used technique, and to perform a meta-analysis. Methods The Embase, PubMed, and Cochrane databases were searched for trials comparing the outcomes of TPS with NKPP up till December 2016. A meta-analysis focusing on outcome (cannulation success, post-endoscopic retrograde cholangiopancreatography (ERCP) pancreatitis (PEP), post-procedural bleeding, and total adverse events) was performed. The population, intervention, comparison, outcome (PICO) format was used to compare these cannulation approaches. Five prospective and eight retrospective studies were included in our meta-analysis. Results NKPP has a significantly lower success rate (odds ratio [OR] 0.50, P = 0.046; relative risk [RR] 0.92, P = 0.03) and a higher rate of bleeding complications (OR 2.24, P = 0.02; RR 2.18, P = 0.02) than TPS. However, no significant differences were found in PEP (OR 0.79, P = 0.24; RR 0.80, P = 0.19), perforation (risk difference [RD] 0.01, P = 0.23), or total complication rates (OR 1.22, P = 0.44; RR 1.17, P = 0.47). Conclusion While TPS has a higher success rate in difficult biliary access and causes less bleeding than NKPP, there are no differences in PEP, perforation, or total complication rates between the two approaches. We conclude that TPS, in the hands of expert endoscopists, is a safe procedure, which should be used more widely in patients with difficult biliary access.

Common variants in the CLDN2-MORC4 and PRSS1-PRSS2 loci confer susceptibility to acute pancreatitis

BACKGROUND/OBJECTIVES Acute pancreatitis (AP) is one of the most common gastrointestinal disorders often requiring hospitalization. Frequent aetiologies are gallstones and alcohol abuse. In contrast to chronic pancreatitis (CP) few robust genetic associations have been described. Here we analysed whether common variants in the CLDN2-MORC4 and the PRSS1-PRSS2 locus that increase recurrent AP and CP risk associate with AP. METHODS We screened 1462 AP patients and 3999 controls with melting curve analysis for SNPs rs10273639 (PRSS1-PRSS2), rs7057398 (RIPPLY), and rs12688220 (MORC4). Calculations were performed for the overall group, aetiology, and gender sub-groups. To examine genotype-phenotype relationships we performed several meta-analyses. RESULTS Meta-analyses of all AP patients depicted significant (p-value < 0.05) associations for rs10273639 (odds ratio (OR) 0.88, 95% confidence interval (CI) 0.81-0.97, p-value 0.01), rs7057398 (OR 1.27, 95% CI 1.07-1.5, p-value 0.005), and rs12688220 (OR 1.32, 95% CI 1.12-1.56, p-value 0.001). For the different aetiology groups a significant association was shown for rs10273639 (OR 0.76, 95% CI 0.63-0.92, p-value 0.005), rs7057398 (OR 1.43, 95% CI 1.07-1.92, p-value 0.02), and rs12688220 (OR 1.44, 95% CI 1.07-1.93, p-value 0.02) in the alcoholic sub-group only. CONCLUSIONS The association of CP risk variants with different AP aetiologies, which is strongest in the alcoholic AP group, might implicate common pathomechanisms most likely between alcoholic AP and CP.