Detailed Characteristics of Post-discharge Mortality in Acute Pancreatitis.

BACKGROUND & AIMS: The in-hospital survival of patients suffering from acute pancreatitis (AP) is 95% to 98%. However, there is growing evidence that patients discharged after AP may be at risk of serious morbidity and mortality. Here, we aimed to investigate the risk, causes, and predictors of the most severe consequence of the post-AP period: mortality. METHODS: A total of 2613 well-characterized patients from 25 centers were included and followed by the Hungarian Pancreatic Study Group between 2012 and 2021. A general and a hospital-based population was used as the control group. RESULTS: After an AP episode, patients have an approximately threefold higher incidence rate of mortality than the general population (0.0404 vs 0.0130 person-years). First-year mortality after discharge was almost double than in-hospital mortality (5.5% vs 3.5%), with 3.0% occurring in the first 90-day period. Age, comorbidities, and severity were the most significant independent risk factors for death following AP. Furthermore, multivariate analysis identified creatinine, glucose, and pleural fluid on admission as independent risk factors associated with post-discharge mortality. In the first 90-day period, cardiac failure and AP-related sepsis were among the main causes of death following discharge, and cancer-related cachexia and non-AP-related infection were the key causes in the later phase. CONCLUSION: Almost as many patients in our cohort died in the first 90-day period after discharge as during their hospital stay. Evaluation of cardiovascular status, follow-up of local complications, and cachexia-preventing oncological care should be an essential part of post-AP patient care. Future study protocols in AP must include at least a 90-day follow-up period after discharge.

Type 1 Autoimmune Pancreatitis in Europe: Clinical Profile and Response to Treatment.

BACKGROUND & AIMS: Autoimmune pancreatitis (AIP) is an immune-mediated disease of the pancreas with distinct pathophysiology and manifestations. Our aims were to characterize type 1 AIP in a large pan-European cohort and study the effectiveness of current treatment regimens. METHODS: We retrospectively analyzed adults diagnosed since 2005 with type 1 or not-otherwise-specified AIP in 42 European university hospitals. Type 1 AIP was uniformly diagnosed using specific diagnostic criteria. Patients with type 2 AIP and those who had undergone pancreatic surgery were excluded. The primary end point was complete remission, defined as the absence of clinical symptoms and resolution of the index radiologic pancreatic abnormalities attributed to AIP. RESULTS: We included 735 individuals with AIP (69% male; median age, 57 years; 85% White). Steroid treatment was started in 634 patients, of whom 9 (1%) were lost to follow-up. The remaining 625 had a 79% (496/625) complete, 18% (111/625) partial, and 97% (607/625) cumulative remission rate, whereas 3% (18/625) did not achieve remission. No treatment was given in 95 patients, who had a 61% complete (58/95), 19% partial (18/95), and 80% cumulative (76/95) spontaneous remission rate. Higher (≥0.4 mg/kg/day) corticosteroid doses were no more effective than lower (<0.4 mg/kg/day) doses (odds ratio, 0.428; 95% confidence interval, 0.054-3.387) and neither was a starting dose duration >2 weeks (odds ratio, 0.908; 95% confidence interval, 0.818-1.009). Elevated IgG4 levels were independently associated with a decreased chance of complete remission (odds ratio, 0.639; 95% confidence interval, 0.427-0.955). Relapse occurred in 30% of patients. Relapses within 6 months of remission induction were independent of the steroid-tapering duration, induction treatment duration, and total cumulative dose. CONCLUSIONS: Patients with type 1 AIP and elevated IgG4 level may need closer monitoring. For remission induction, a starting dose of 0.4 mg/kg/day for 2 weeks followed by a short taper period seems effective. This study provides no evidence to support more aggressive regimens.

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

The European Society of Gastrointestinal Endoscopy (ESGE) has recognized the need to formalize and enhance training in diagnostic 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 diagnostic EUS. This curriculum is set out in terms of the prerequisites prior to training; the 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 have achieved competence in upper gastrointestinal endoscopy before training in diagnostic EUS. 2: The development of diagnostic EUS skills by methods that do not involve patients is advisable, but not mandatory, prior to commencing formal training in diagnostic EUS. 3: A trainee's principal trainer should be performing adequate volumes of diagnostic EUSs to demonstrate maintenance of their own competence. 4: Training centers for diagnostic EUS should offer expertise, as well as a high volume of procedures per year, to ensure an optimal level of quality for training. Under these conditions, training centers should be able to provide trainees with a sufficient wealth of experience in diagnostic EUS for at least 12 months. 5: Trainees should engage in formal training and supplement this with a range of learning resources for diagnostic EUS, including EUS-guided fine-needle aspiration and biopsy (FNA/FNB). 6: EUS training should follow a structured syllabus to guide the learning program. 7: A minimum procedure volume should be offered to trainees during diagnostic EUS training to ensure that they have the opportunity to achieve competence in the technique. To evaluate competence in diagnostic EUS, trainees should have completed a minimum of 250 supervised EUS procedures: 80 for luminal tumors, 20 for subepithelial lesions, and 150 for pancreaticobiliary lesions. At least 75 EUS-FNA/FNBs should be performed, including mostly pancreaticobiliary lesions. 8: Competence assessment in diagnostic EUS should take into consideration not only technical skills, but also cognitive and integrative skills. A reliable valid assessment tool should be used regularly during diagnostic EUS training to track the acquisition of competence and to support trainee feedback. 9: A period of supervised practice should follow the start of independent activity. Supervision can be delivered either on site if other colleagues are already practicing EUS or by maintaining contacts with the training center and/or other EUS experts. 10: Key performance measures including the annual number of procedures, frequency of obtaining a diagnostic sample during EUS-FNA/FNB, and adverse events should be recorded within an electronic documentation system and evaluated.

Comparison of therapeutic efficacy and treatment costs of self-expandable metal stents and plastic stents for management of malignant biliary obstruction.

BACKGROUND: According to the European Society of Gastrointestinal Endoscopy guidelines, self-expandable metal stents (SEMSs) are preferable to plastic stents (PSs) in the management of pancreatic cancer, regardless of cancer stage. The aim of this study was to compare the therapeutic efficacy and treatment costs of SEMS and PS in the management of malignant biliary obstruction. METHODS: One hundred and thirty-five patients who underwent endoscopic stent placement were retrospectively enrolled and divided into PS (41 patients), primary SEMS (39 patients) and secondary SEMS (55 patients) groups. We determined the technical and functional success rate, stent patency, and cumulative treatment cost. RESULTS: A total of 111 SEMSs and 153 PSs were placed with similar technical (100% vs. 98.69%) and functional success rate (90.10% vs. 86.27%) but with different stent patency (10.28 vs. 22.16 weeks; p < 0.001). Multiple PS implantations and larger stent diameter increased the length of stent patency compared to 7-Fr PSs (10.88 vs. 10.55 vs. 7.63 weeks, respectively). The cumulative treatment cost of patients with different survival times did not differ significantly between groups, however, among patients surviving 2-4 months it was higher in PS group than primary SEMS and secondary SEMS groups (2888€ vs. 2258€ vs. 2144€, respectively, p = 0.3369) due to increased number of biliary reintervention (2.08 ± 1.04 vs. 1.20 ± 0.42 vs. 1.50 ± 0.53; p < 0.0274) and longer hospital stay (15.77 ± 10.14 vs. 8.70 ± 7.70 vs. 8.50 ± 6.17 days, p = 0.0527). CONCLUSIONS: In view of treatment costs, the consequences of illness, and the processes of the health care system, SEMS implantation is recommended regardless of patients' life expectancy.

The EFFect of dietary fat content on the recurrence of pancreaTitis (EFFORT): Protocol of a multicenter randomized controlled trial.

BACKGROUND: Around 20% of patients with acute pancreatitis (AP) will develop acute recurrent pancreatitis (ARP) and 10% will progress to chronic pancreatitis. While interventions to avoid recurrences exist for the two most common causes - abstinence for alcoholic and cholecystectomy for biliary pancreatitis - the are no known preventive measures in idiopathic ARP. Though it is not included in any of the guidelines, a low-fat diet is often recommended. Our aim is to test dietary fat reduction's effect on AP recurrence in a randomized controlled setting, in order to provide high-quality evidence for the validity of such an intervention. METHODS, DESIGN: Participants with at least 2 episodes of AP in the preceding 2 years of which the last episode was idiopathic will be randomized to one of two diets with different fat contents: a 'reduced fat diet' (15% fat, 65% carbohydrate, 20% protein) and a 'standard healthy diet' (30% fat, 50% carbohydrate, 20% protein; based on WHO recommendations). Participants will be followed-up for 2 years (visits will be scheduled for months 3, 6, 12, 18 and 24) during which they will receive a repeated session of nutritional guidance, complete food frequency questionnaires and data on relapse, mortality, BMI, cardiovascular parameters and serum lipid values will be collected. DISCUSSION: This study will determine the effect of modifying the dietary fat content on AP recurrence, mortality, serum lipids and weight loss in idiopathic cases.

Surgical outcome of percutaneous transhepatic gallbladder drainage in acute cholecystitis: Ten years' experience at a tertiary care centre.

BACKGROUND: Percutaneous transhepatic gallbladder drainage (PTGBD) plays an important role in the treatment of elderly patients and/or patients in poor health with acute cholecystitis (AC). The primary aim of this study is to determine how these factors influence the clinical outcome of PTGBD. Moreover, we assessed the timing and results of subsequent cholecystectomies. PATIENTS AND METHODS: We retrospectively examined the results of 162 patients undergoing PTGBD between 2010 and 2020 (male-female ratio: 51.23% vs. 48.77%; mean age: 71.43 ± 13.22 years). Patient's performance status and intervention outcomes were assessed with clinical success rates (CSR) and in-hospital mortality. The conversion rate (CR) of possible urgent or delayed, elective laparoscopic cholecystectomies (LC) after PTGBD were analysed. RESULTS: PTGBD was the definitive treatment in 42.18% of patients, while it was a bridging therapy prior to cholecystectomy (CCY) for the other patients. CSR was 87.97%, it was only 64.29% in grade III AC. In 9.87% of the cases, urgent LC was necessary after PTGBD, and its conversion rate was approximately equal to that of elective LC (18.18 vs. 17.46%, respectively, p = 0.2217). Overall, the post-PTGBD in-hospital mortality was 11.72%, while the same figure was 0% for grade I AC, 7.41% for grade II and 40.91% for grade III. Based on logistic regression analyses, in-hospital mortality (OR 6.07; CI 1.79-20.56), clinical progression (OR 7.62; CI 2.64-22.05) and the need for emergency CCY (OR 14.75; CI 3.07-70.81) were mostly determined by AC severity grade. CONCLUSION: PTGBD is an easy-to-perform intervention with promising clinical success rates in the treatment of acute cholecystitis. After PTGBD, the level of gallbladder inflammation played a decisive role in the course of AC. In a severe, grade III inflammation, we have to consider low CSR and high mortality.

Common calcium-sensing receptor (CASR) gene variants do not modify risk for chronic pancreatitis in a Hungarian cohort.

The calcium-sensing receptor (CASR) is expressed in the pancreas where it might regulate calcium concentrations in pancreatic secretions. Two independent studies reported conflicting results claiming that commonly occurring missense variants of the CASR gene are risk factors for chronic pancreatitis (CP). Here, we attempted to replicate the association between CASR variants and CP. We analyzed 337 patients and 840 controls from the Hungarian National Pancreas Registry either by direct sequencing of exon 7 and the flanking noncoding regions or by TaqMan SNP genotyping assays. We identified two common missense variants, c.2956G>T (p.A986S), and c.2968A>G (p.R990G), three low-frequency variants, c.3031C>G (p.Q1011E), c.2610G>A (p.E870=) and c.∗60T>A, and 8 rare variants including the novel variant c.1895G>A (p.G632D). When allelic or genotype distributions were considered, none of the CASR variants associated with CP. Subgroup analysis of nonalcoholic versus alcoholic patients revealed no disease association either. Our results demonstrate that common CASR variants do not modify the risk for CP and should not be considered as genetic risk factors in the clinical setting.

ERCP is more challenging in cases of acute biliary pancreatitis than in acute cholangitis - Analysis of the Hungarian ERCP registry data.

BACKGROUND: Endoscopic retrograde cholangiopancreatography (ERCP) is an important therapeutic modality in acute biliary pancreatitis (ABP) cases with cholangitis or ongoing common bile duct obstruction. Theoretically, inflammation of the surrounding tissues would result in a more difficult procedure. No previous studies examined this hypothesis. OBJECTIVES: ABP and acute cholangitis (AC) without ABP cases were compared to assess difficulty of ERCP. METHODS: The rate of successful biliary access, advanced cannulation method, adverse events, cannulation and fluoroscopy time were compared in 240 ABP cases and 250 AC cases without ABP. Previous papillotomy, altered gastroduodenal anatomy, and cases with biliary stricture were excluded. RESULTS: Significantly more pancreatic guidewire manipulation (adjusted odds ratio (aOR) 1.921 [1.241-2.974]) and prophylactic pancreatic stent use (aOR 4.687 [2.415-9.098]) were seen in the ABP than in AC group. Average cannulation time in the ABP patients (248 vs. 185 s; p = 0.043) were longer than in AC cases. No difference was found between biliary cannulation and adverse events rates. CONCLUSION: ERCP in ABP cases seem to be more challenging than in AC. Difficult biliary access is more frequent in the ABP cases which warrants the involvement of an experienced endoscopist.

Early occurrence of pseudocysts in acute pancreatitis - A multicenter international cohort analysis of 2275 cases.

BACKGROUND: Pseudocysts being the most frequent local complications of acute pancreatitis (AP) have substantial effect on the disease course, hospitalization and quality of life of the patient. Our study aimed to understand the effects of pre-existing (OLD-P) and newly developed (NEW-P) pseudocysts on AP. METHODS: Data were extracted from the Acute Pancreatitis Registry organized by the Hungarian Pancreatic Study Group (HPSG). 2275 of 2461 patients had uploaded information concerning pancreatic morphology assessed by imaging technique. Patients were divided into "no pseudocyst" (NO-P) group, "old pseudocyst" (OLD-P) group, or "newly developed pseudocyst" (NEW-P) groups. RESULTS: The median time of new pseudocyst development was nine days from hospital admission and eleven days from the beginning of the abdominal pain. More NEW-P cases were severe (15.9% vs 4.7% in the NO-P group p < 0.001), with longer length of hospitalization (LoH) (median: 14 days versus 8 days, p < 0.001), and were associated with several changed laboratory parameters. OLD-P was associated with male gender (72.2% vs. 56.1%, p = 0.0014), alcoholic etiology (35.2% vs. 19.8% in the NO-P group), longer hospitalization (median: 10 days, p < 0.001), a previous episode of AP (p < 0.001), pre-existing diagnosis of chronic pancreatitis (CP) (p < 0.001), current smoking (p < 0.001), and increased alcohol consumption (unit/week) (p = 0.014). CONCLUSION: Most of the new pseudocysts develop within two weeks. Newly developing pseudocysts are associated with a more severe disease course and increased length of hospitalization. Pre-existing pseudocysts are associated with higher alcohol consumption and smoking. Because CP is more frequently associated with a pre-existing pseudocyst, these patients need closer attention after AP.

Endoscopic tissue sampling - Part 2: Lower gastrointestinal tract. European Society of Gastrointestinal Endoscopy (ESGE) Guideline.

1: ESGE suggests performing segmental biopsies (at least two from each segment), which should be placed in different specimen containers (ileum, cecum, ascending, transverse, descending, and sigmoid colon, and rectum) in patients with clinical and endoscopic signs of colitis.Weak recommendation, low quality of evidence. 2: ESGE recommends taking two biopsies from the right hemicolon (ascending and transverse colon) and, in a separate container, two biopsies from the left hemicolon (descending and sigmoid colon) when microscopic colitis is suspected.Strong recommendation, low quality of evidence. 3: ESGE recommends pancolonic dye-based chromoendoscopy or virtual chromoendoscopy with targeted biopsies of any visible lesions during surveillance endoscopy in patients with inflammatory bowel disease. Strong recommendation, moderate quality of evidence. 4: ESGE suggests that, in high risk patients with a history of colonic neoplasia, tubular-appearing colon, strictures, ongoing therapy-refractory inflammation, or primary sclerosing cholangitis, chromoendoscopy with targeted biopsies can be combined with four-quadrant non-targeted biopsies every 10 cm along the colon. Weak recommendation, low quality of evidence. 5: ESGE recommends that, if pouch surveillance for dysplasia is performed, visible abnormalities should be biopsied, with at least two biopsies systematically taken from each of the afferent ileal loop, the efferent blind loop, the pouch, and the anorectal cuff.Strong recommendation, low quality of evidence. 6: ESGE recommends that, in patients with known ulcerative colitis and endoscopic signs of inflammation, at least two biopsies be obtained from the worst affected areas for the assessment of activity or the presence of cytomegalovirus; for those with no evident endoscopic signs of inflammation, advanced imaging technologies may be useful in identifying areas for targeted biopsies to assess histologic remission if this would have therapeutic consequences. Strong recommendation, low quality of evidence. 7: ESGE suggests not biopsying endoscopically visible inflammation or normal-appearing mucosa to assess disease activity in known Crohn's disease.Weak recommendation, low quality of evidence. 8: ESGE recommends that adequately assessed colorectal polyps that are judged to be premalignant should be fully excised rather than biopsied.Strong recommendation, low quality of evidence. 9: ESGE recommends that, where endoscopically feasible, potentially malignant colorectal polyps should be excised en bloc rather than being biopsied. If the endoscopist cannot confidently perform en bloc excision at that time, careful representative images (rather than biopsies) should be taken of the potential focus of cancer, and the patient should be rescheduled or referred to an expert center.Strong recommendation, low quality of evidence. 10: ESGE recommends that, in malignant lesions not amenable to endoscopic excision owing to deep invasion, six carefully targeted biopsies should be taken from the potential focus of cancer.Strong recommendation, low quality of evidence.

Endoscopic tissue sampling - Part 1: Upper gastrointestinal and hepatopancreatobiliary tracts. European Society of Gastrointestinal Endoscopy (ESGE) Guideline.

1: ESGE recommends that, where there is a suspicion of eosinophilic esophagitis, at least six biopsies should be taken, two to four biopsies from the distal esophagus and two to four biopsies from the proximal esophagus, targeting areas with endoscopic mucosal abnormalities. Distal and proximal biopsies should be placed in separate containers.Strong recommendation, low quality of evidence. 2: ESGE recommends obtaining six biopsies, including from the base and edge of the esophageal ulcers, for histologic analysis in patients with suspected viral esophagitis.Strong recommendation, low quality of evidence. 3: ESGE recommends at least six biopsies are taken in cases of suspected advanced esophageal cancer and suspected advanced gastric cancer.Strong recommendation, moderate quality of evidence. 4: ESGE recommends taking only one to two targeted biopsies for lesions in the esophagus or stomach that are potentially amenable to endoscopic resection (Paris classification 0-I, 0-II) in order to confirm the diagnosis and not compromise subsequent endoscopic resection.Strong recommendation, low quality of evidence. 5: ESGE recommends obtaining two biopsies from the antrum and two from the corpus in patients with suspected Helicobacter pylori infection and for gastritis staging.Strong recommendation, low quality of evidence. 6: ESGE recommends biopsies from or, if endoscopically resectable, resection of gastric adenomas.Strong recommendation, moderate quality of evidence. 7: ESGE recommends fine-needle aspiration (FNA) and fine-needle biopsy (FNB) needles equally for sampling of solid pancreatic masses.Strong recommendation, high quality evidence. 8: ESGE suggests performing peroral cholangioscopy (POC) and/or endoscopic ultrasound (EUS)-guided tissue acquisition in indeterminate biliary strictures. For proximal and intrinsic strictures, POC is preferred. For distal and extrinsic strictures, EUS-guided sampling is preferred, with POC where this is not diagnostic.Weak recommendation, low quality evidence. 9: ESGE suggests obtaining possible non-neoplastic biopsies before sampling suspected malignant lesions to prevent intraluminal spread of malignant disease.Weak recommendation, low quality of evidence. 10: ESGE suggests dividing EUS-FNA material into smears (two per pass) and liquid-based cytology (LBC), or the whole of the EUS-FNA material can be processed as LBC, depending on local experience.Weak recommendation, low quality evidence.

Esophageal stenting for benign and malignant disease: European Society of Gastrointestinal Endoscopy (ESGE) Guideline - Update 2021.

MALIGNANT DISEASE: 1: ESGE recommends placement of partially or fully covered self-expandable metal stents (SEMSs) for palliation of malignant dysphagia over laser therapy, photodynamic therapy, and esophageal bypass.Strong recommendation, high quality evidence. 2 : ESGE recommends brachytherapy as a valid alternative, alone or in addition to stenting, in esophageal cancer patients with malignant dysphagia and expected longer life expectancy.Strong recommendation, high quality evidence. 3: ESGE recommends esophageal SEMS placement for sealing malignant tracheoesophageal or bronchoesophageal fistulas. Strong recommendation, low quality evidence. 4 : ESGE does not recommend SEMS placement as a bridge to surgery or before preoperative chemoradiotherapy because it is associated with a high incidence of adverse events. Other options such as feeding tube placement are preferable. Strong recommendation, low quality evidence. BENIGN DISEASE: 5: ESGE recommends against the use of SEMSs as first-line therapy for the management of benign esophageal strictures because of the potential for adverse events, the availability of alternative therapies, and their cost. Strong recommendation, low quality evidence. 6: ESGE suggests consideration of temporary placement of self-expandable stents for refractory benign esophageal strictures. Weak recommendation, moderate quality evidence. 7: ESGE suggests that fully covered SEMSs be preferred over partially covered SEMSs for the treatment of refractory benign esophageal strictures because of their very low risk of embedment and ease of removability. Weak recommendation, low quality evidence. 8: ESGE recommends the stent-in-stent technique to remove partially covered SEMSs that are embedded in the esophageal wall. Strong recommendation, low quality evidence. 9: ESGE recommends that temporary stent placement can be considered for the treatment of leaks, fistulas, and perforations. No specific type of stent can be recommended, and the duration of stenting should be individualized. Strong recommendation, low quality of evidence. 10 : ESGE recommends considering placement of a fully covered large-diameter SEMS for the treatment of esophageal variceal bleeding refractory to medical, endoscopic, and/or radiological therapy, or as initial therapy for patients with massive bleeding. Strong recommendation, moderate quality evidence.

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

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.

EarLy Elimination of Fatty Acids iN hypertriglyceridemia-induced acuTe pancreatitis (ELEFANT trial): Protocol of an open-label, multicenter, adaptive randomized clinical trial.

INTRODUCTION: Acute pancreatitis (AP) is a life-threatening inflammatory disease, with no specific pharmacological treatment. However, concerning some etiologies, early specific intervention (such as ERCP in biliary AP) has proven to be remarkably beneficial. Hypertriglyceridemia (HTG) induces severe pancreatic damage by several direct (cellular damage) and indirect (deterioration of microcirculation) mechanisms. Published data suggest that early removal of triglycerides (TGs) and toxic free fatty acids (FFAs) may be advantageous; however, high-quality evidence is still missing in the literature. METHODS: Design: ELEFANT is a randomized controlled, multicenter, international trial testing the concept that early elimination of TGs and FFAs from the blood is beneficial in HTG-AP. The study will be performed with the adaptive "drop-the-loser" design, which supports the possibility of dropping the inferior treatment arm, based on the results of the interim analysis. Patients with HTG-AP defined by TG level over 11.3 mmol/l (1000 mg/dL) are randomized into three groups: (A) patients who undergo plasmapheresis and receive aggressive fluid resuscitation; (B) patients who receive insulin and heparin treatment with aggressive fluid resuscitation; and (C) patients with aggressive fluid resuscitation. Please note that all intervention must be started within 48 h from the onset of abdominal pain. Exclusion criteria are designed logically to decrease the possibility of any distorting effects of other diseases. The composite primary endpoint will include both severity and mortality. RESULTS: Our null hypothesis is that early elimination of HTG and FFAs reduces the risk of mortality and severity of AP. Sample size calculation suggests that 495 patients will need to be enrolled in order to confirm or reject the hypothesis with a 10% dropout, 80% power and 95% significance level. The general safety and quality checks required for high-quality evidence will be adhered to. The study will be organized between February 2020 and December 2025. CONCLUSION: Our study would provide the first direct evidence for or against early intervention in HTG-induced AP.

Development of disturbance of consciousness is associated with increased severity in acute pancreatitis.

BACKGROUND: Disturbance of consciousness (DOC) may develop in acute pancreatitis (AP). In clinical practice, it is known that DOC may worsen the patient's condition, but we have no exact data on how DOC affects the outcome of AP. METHODS: From the Hungarian Pancreatic Study Groups' AP registry, 1220 prospectively collected cases were analyzed, which contained exact data on DOC, included patients with confusion, delirium, convulsion, and alcohol withdrawal, answering a post hoc defined research question. Patients were separated to Non-DOC and DOC, whereas DOC was further divided into non-alcohol related DOC (Non-ALC DOC) and ALC DOC groups. For statistical analysis, independent sample t-test, Mann-Whitney, Chi-squared, or Fisher exact test were used. RESULTS: From the 1220 patients, 47 (3.9%) developed DOC, 23 (48.9%) cases were ALC DOC vs. 24 (51.1%) Non-ALC DOC. Analysis between the DOC and Non-DOC groups showed a higher incidence of severe AP (19.2% vs. 5.3%, p < 0.001), higher mortality (14.9% vs. 1.7%, p < 0.001), and a longer length of hospitalization (LOH) (Me = 11; IQR: 8-17 days vs. Me = 9; IQR: 6-13 days, p = 0.049) respectively. Patients with ALC DOC developed more frequently moderate AP vs. Non-ALC DOC (43.5% vs. 12.5%), while the incidence of severe AP was higher in Non-ALC vs. ALC DOC group (33.3% vs. 4.4%) (p < 0.001). LOH showed a tendency to be longer in Non-ALC DOC compared to ALC DOC, respectively (Me:13; IQR:7-20 days vs. Me:9.5; IQR:8-15.5 days, p = 0.119). CONCLUSION: DOC during AP is associated with a higher rate of moderate and severe AP and increases the risk of mortality.

Acid suppression therapy, gastrointestinal bleeding and infection in acute pancreatitis - An international cohort study.

BACKGROUND: Acid suppressing drugs (ASD) are generally used in acute pancreatitis (AP); however, large cohorts are not available to understand their efficiency and safety. Therefore, our aims were to evaluate the association between the administration of ASDs, the outcome of AP, the frequency of gastrointestinal (GI) bleeding and GI infection in patients with AP. METHODS: We initiated an international survey and performed retrospective data analysis on AP patients hospitalized between January 2013 and December 2018. RESULTS: Data of 17,422 adult patients with AP were collected from 59 centers of 23 countries. We found that 23.3% of patients received ASDs before and 86.6% during the course of AP. ASDs were prescribed to 57.6% of patients at discharge. ASD administration was associated with more severe AP and higher mortality. GI bleeding was reported in 4.7% of patients, and it was associated with pancreatitis severity, mortality and ASD therapy. Stool culture test was performed in 6.3% of the patients with 28.4% positive results. Clostridium difficile was the cause of GI infection in 60.5% of cases. Among the patients with GI infections, 28.9% received ASDs, whereas 24.1% were without any acid suppression treatment. GI infection was associated with more severe pancreatitis and higher mortality. CONCLUSIONS: Although ASD therapy is widely used, it is unlikely to have beneficial effects either on the outcome of AP or on the prevention of GI bleeding during AP. Therefore, ASD therapy should be substantially decreased in the therapeutic management of AP.

Hypertriglyceridemia-induced acute pancreatitis: A prospective, multicenter, international cohort analysis of 716 acute pancreatitis cases.

BACKGROUND: Hypertriglyceridemia is the third most common cause of acute pancreatitis (AP). It has been shown that hypertriglyceridemia aggravates the severity and related complications of AP; however, detailed analyses of large cohorts are contradictory. Our aim was to investigate the dose-dependent effect of hypertriglyceridemia on AP. METHODS: AP patients over 18 years old who underwent triglyceride measurement within the initial three days were included into our cohort analysis from a prospective international, multicenter AP registry operated by the Hungarian Pancreatic Study Group. Data on 716 AP cases were analyzed. Six groups were created based on the highest triglyceride level (<1.7 mmol/l, 1.7-2.19 mmol/l, 2.2-5.59 mmol/l, 5.6-11.29 mmol/l, 11.3-22.59 mmol/l, ≥22.6 mmol/l). RESULTS: Hypertriglyceridemia (≥1.7 mmol/l) presented in 30.6% of the patients and was significantly and dose-dependently associated with younger age and male gender. In 7.7% of AP cases, hypertriglyceridemia was considered as a causative etiological factor (≥11.3 mmol/l); however, 43.6% of these cases were associated with other etiologies (alcohol and biliary). Hypertriglyceridemia was significantly and dose-dependently related to obesity and diabetes. The rates of local complications and organ failure and maximum CRP level were significantly and dose-dependently raised by hypertriglyceridemia. Triglyceride above 11.3 mmol/l was linked to a significantly higher incidence of moderately severe AP and longer hospital stay, whereas triglyceride over 22.6 mmol/l was significantly associated with severe AP as well. CONCLUSION: Hypertriglyceridemia dose-dependently aggravates the severity and related complications of AP. Diagnostic workup for hypertriglyceridemia requires better awareness regardless of the etiology of AP.

Slow-pull technique yields better quality smears: prospective comparison of slow-pull and standard suction techniques of endoscopic ultrasound-guided fine-needle aspiration.

BACKGROUND: Diagnostic accuracy and quality of smears obtained by endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) are influenced by characteristics of suction and examined organ. AIMS AND METHODS: Efficiency of EUS-FNA and quality of smears obtained by slow-pull (SP) and standard suction (SS) techniques was prospectively compared in the sampling of pancreatic (N = 56) and extrapancreatic (N = 145) tumors. RESULTS: SS technique resulted in a higher number of smear pairs both in pancreatic (1.74 vs. 3.19; p < 0.001) and extrapancreatic tumors (1.62 vs. 3.28; p < 0.001); however, it decreased the proportion of diagnostic smears (46.69% vs. 36.52%; p = 0.002 and 49.17% vs. 30.67%; p < 0.001) and increased the bloodiness (1.51 vs. 2.07; p < 0.001 and 1.48 vs. 2.05; p < 0.001). In pancreatic cancers, no difference was observed in terms of diagnostic accuracy (81.38% vs. 83.45%) and cellularity (1.44 vs. 1.27; p = 0.067); however, they were substantially higher in extrapancreatic tumors using SP technique (71.41% vs. 60.71% and 1.34 vs. 0.77; p < 0.001). Only SP technique resulted in a significant difference between examiners in terms of technical success rate and quality of smears without any decrease of diagnostic accuracy. CONCLUSIONS: SP technique yields better quality smears independently from tumors characteristics; however, it shows significant examiner-dependency. SS technique reduces the diagnostic accuracy of sampling in extrapancreatic tumors.

Antibiotic therapy in acute pancreatitis: From global overuse to evidence based recommendations.

BACKGROUND: Unwarranted administration of antibiotics in acute pancreatitis presents a global challenge. The clinical reasoning behind the misuse is poorly understood. Our aim was to investigate current clinical practices and develop recommendations that guide clinicians in prescribing antibiotic treatment in acute pancreatitis. METHODS: Four methods were used. 1) Systematic data collection was performed to summarize current evidence; 2) a retrospective questionnaire was developed to understand the current global clinical practice; 3) five years of prospectively collected data were analysed to identify the clinical parameters used by medical teams in the decision making process, and finally; 4) the UpToDate Grading of Recommendations, Assessment, Development and Evaluation (GRADE) system was applied to provide evidence based recommendations for healthcare professionals. RESULTS: The systematic literature search revealed no consensus on the start of AB therapy in patients with no bacterial culture test. Retrospective data collection on 9728 patients from 22 countries indicated a wide range (31-82%) of antibiotic use frequency in AP. Analysis of 56 variables from 962 patients showed that clinicians initiate antibiotic therapy based on increased WBC and/or elevated CRP, lipase and amylase levels. The above mentioned four laboratory parameters showed no association with infection in the early phase of acute pancreatitis. Instead, procalcitonin levels proved to be a better biomarker of early infection. Patients with suspected infection because of fever had no benefit from antibiotic therapy. CONCLUSIONS: The authors formulated four consensus statements to urge reduction of unjustified antibiotic treatment in acute pancreatitis and to use procalcitonin rather than WBC or CRP as biomarkers to guide decision-making.

Prospective comparison of slow-pull and standard suction techniques of endoscopic ultrasound-guided fine needle aspiration in the diagnosis of solid pancreatic cancer.

BACKGROUND: The usage of endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) for the diagnosis of solid pancreatic cancer is increasing, however mainly retrospective studies are available about the detailed methods of sampling. METHODS: To compare prospectively the diagnostic yield of EUS-FNA samples obtained with slow-pull (SP) and with standard suction technique (SS). RESULTS: EUS-FNA sampling was diagnostic in 72 of 92 cases (78.3%). Diagnostic yield was 67.4% in the SS and 65.2% in the SP group. The number of smear pairs (1.84 vs. 3.56; p < 0.001) and blood contamination (1.50 vs. 2.19; p < 0.001) were significantly higher in the SS group, which resulted in lower rate of diagnostic samples (41.8% vs. 30.0%; p = 0.003). There was no difference in the cellularity (1.58 vs. 1.37; p = 0.2554), or in the sensitivity and specificity in the identification of malignancy between SP and SS subgroups (69.9, 100% vs. 73.5, 100%). Histological samples were obtained in 60 cases (with SP: 49 cases; with SS: 46 cases). There was no difference in the diagnostic yield of histological samples between the groups (63 and 58.7%). CONCLUSION: The diagnostic yield, the cellularity of smears and the rate of acquiring sufficient histological material are similar in the SP and SS group, but due to lower bloodiness and decreased number of slides, the pathological diagnosis is faster and more cost-effective.