Tailoring the Use of Central Pancreatectomy Through Prediction Models for Major Morbidity and Postoperative Diabetes: International Retrospective Multicenter Study.

OBJECTIVE: To develop a prediction model for major morbidity and endocrine dysfunction after CP which could help in tailoring the use of this procedure. SUMMARY BACKGROUND DATA: Central pancreatectomy (CP) is a parenchyma-sparing alternative to distal pancreatectomy for symptomatic benign and pre-malignant tumors in body and neck of the pancreas CP lowers the risk of new-onset diabetes and exocrine pancreatic insufficiency compared to distal pancreatectomy but it is thought to increase the risk of short-term complications including postoperative pancreatic fistula (POPF). METHODS: International multicenter retrospective cohort study including patients from 51 centers in 19 countries (2010-2021). Primary endpoint was major morbidity. Secondary endpoints included POPF grade B/C, endocrine dysfunction, and the use of pancreatic enzymes. Two risk model were designed for major morbidity and endocrine dysfunction utilizing multivariable logistic regression and internal and external validation. RESULTS: 838 patients after CP were included (301 (36%) minimally invasive) and major morbidity occurred in 248 (30%) patients, POPF B/C in 365 (44%), and 30-day mortality in 4 (1%). Endocrine dysfunction in 91 patients (11%) and use of pancreatic enzymes in 108 (12%). The risk model for major morbidity included male sex, age, BMI, and ASA score≥3. The model performed acceptable with an area under curve (AUC) of 0.72(CI:0.68-0.76). The risk model for endocrine dysfunction included higher BMI and male sex and performed well (AUC:0.83 (CI:0.77-0.89)). CONCLUSIONS: The proposed risk models help in tailoring the use of CP in patients with symptomatic benign and premalignant lesions in the body and neck of the pancreas and are readily available via www.pancreascalculator.com.

Quality of life after endoscopic procedures for chronic pancreatitis: A multicentre study.

BACKGROUND: Chronic Pancreatitis (CP) causes morphological changes in the pancreatic tissue, leading to complications and pain, which may require endoscopic interventions. OBJECTIVE: Our aim was to determine the frequency of endoscopic procedures (EP) in CP patients and to analyse pain and quality of life (QoL) in these patients after their EP. METHODS: This study included 1327 CP patients from the Scandinavian Baltic Pancreatic Club (SBPC) database including four countries and eight centres. We analysed patients undergoing EPs and gathered information on the EP, pancreatic function, pain, disease and duration. The EORTC C-30 QoL questionnaire was gathered prospectively and multivariable analysis was conducted on independent parameters between the groups. The reference population had no interventions (n = 870). RESULTS: 260 CP patients (22%) underwent EPs, median one year (range 0-39 years) after CP diagnosis. 68% were males. The median age was 59 (20-90) years. Most common aetiological factors were alcohol in 65% and smoking in 71%. Extracorporeal shock wave lithotripsy (ESWL) was used in 6% of the CP population and in 21% of the EP group. Biliary duct stenting was performed on 37% and pancreatic stenting was performed on 56% of the patients. There was no difference in pain patterns between patients who had pancreatic stenting and the reference population. The EP group had slightly better QoL (p = 0.047), functioning and fewer symptoms than the reference population, in the multivariable analysis there was no interaction effect analysis between the groups. The pancreatic stent group had better QoL and the same amount of pain than the reference group. The patients who needed later surgery (23%) had more pain (p = 0.043) and fatigue (p = 0.021). CONCLUSIONS: One in five of the CP patients underwent EP. These patients scored higher on QoL responses and had better symptom scores. CP patients who had pancreatic stenting performed had the same pain patterns as the reference population. Randomised prospective trials are needed to determine the effect of endoscopy procedures on CP patients.

Editorial for the Special Issue "Acute and Chronic Pancreatitis, Pancreatic Malignancies".

Pancreatic diseases, especially acute pancreatitis and pancreatic cancer, are associated with high rates of complications, difficult treatment that may not always be effective, and high mortality in complex cases [...].

Hypophosphatemia as a prognostic tool for post-hepatectomy liver failure: A systematic review.

BACKGROUND: Post-hepatectomy liver failure (PHLF) is one of the main causes of postoperative mortality and is challenging to predict early in patients after liver resection. Some studies suggest that the postoperative serum phosphorus might predict outcomes in these patients. AIM: To perform a systematic literature review on hypophosphatemia and evaluate it as a prognostic factor for PHLF and overall morbidity. METHODS: This systematic review was performed according to preferred reporting items for systematic reviews and meta-analyses statement. A study protocol for the review was registered in the International Prospective Register of Systematic Reviews database. PubMed, Cochrane and Lippincott Williams & Wilkins databases were systematically searched up to March 31, 2022 for studies analyzing postoperative hypophosphatemia as a prognostic factor for PHLF, overall postoperative morbidity and liver regeneration. The quality assessment of the included cohort studies was performed according to the Newcastle-Ottawa Scale. RESULTS: After final assessment, nine studies (eight retrospective and one prospective cohort study) with 1677 patients were included in the systematic review. All selected studies scored ≥ 6 points according to the Newcastle-Ottawa Scale. Cutoff values of hypophosphatemia varied from < 1 mg/dL to ≤ 2.5 mg/dL in selected studies with ≤ 2.5 mg/dL being the most used defining value. Five studies analyzed PHLF, while the remaining four analyzed overall complications as a main outcome associated with hypophosphatemia. Only two of the selected studies analyzed postoperative liver regeneration, with reported better postoperative liver regeneration in cases of postoperative hypophosphatemia. In three studies hypophosphatemia was associated with better postoperative outcomes, while six studies revealed hypophosphatemia as a predictive factor for worse patient outcomes. CONCLUSION: Changes of the postoperative serum phosphorus level might be useful for predicting outcomes after liver resection. However, routine measurement of perioperative serum phosphorus levels remains questionable and should be evaluated individually.

Postoperative Hypophosphatemia as a Prognostic Factor for Postoperative Pancreatic Fistula: A Systematic Review.

Background and Objectives: Postoperative pancreatic fistula (POPF) is one of the most challenging complications after pancreatic resections, associated with prolonged hospital stay and high mortality. Early identification of pancreatic fistula is necessary for the treatment to be effective. Several prognostic factors have been identified, although it is unclear which one is the most crucial. Some studies show that post-pancreatectomy hypophosphatemia may be associated with the development of POPF. The aim of this systematic review was to determine whether postoperative hypophosphatemia can be used as a prognostic factor for postoperative pancreatic fistula. Materials and Methods: The systematic literature review was performed according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses recommendations (PRISMA) and was registered in the International Prospective Register of Systematic Reviews (PROSPERO). The PubMed, ScienceDirect, and Web of Science databases were systematically searched up to the 31st of January 2022 for studies analyzing postoperative hypophosphatemia as a prognostic factor for POPF. Data including study characteristics, patient characteristics, operation type, definitions of postoperative hypophosphatemia and postoperative pancreatic fistula were extracted. Results: Initially, 149 articles were retrieved. After screening and final assessment, 3 retrospective studies with 2893 patients were included in this review. An association between postoperative hypophosphatemia and POPF was found in all included studies. Patients undergoing distal pancreatectomy were more likely to develop severe hypophosphatemia compared to patients undergoing proximal pancreatectomy. Serum phosphate levels on postoperative day 4 (POD 4) and postoperative day 5 (POD 5) remained significantly lower in patients who developed leak-related complications showing a slower recovery of hypophosphatemia from postoperative day 3 (POD 3) through postoperative day 7 (POD 7). Moreover, body mass index (BMI) higher than 30 kg/m2, soft pancreatic tissue, abnormal white blood cell count on postoperative day 3 (POD 3), and shorter surgery time were associated with leak-related complications (LRC) and lower phosphate levels. Conclusions: Early postoperative hypophosphatemia might be used as a prognostic biomarker for early identification of postoperative pancreatic fistula. However, more studies are needed to better identify significant cut-off levels of postoperative hypophosphatemia and development of hypophosphatemia in the postoperative period.

Dynamic Contrast-Enhanced Magnetic Resonance Imaging for Measuring Perfusion in Pancreatic Ductal Adenocarcinoma and Different Tumor Grade: A Preliminary Single Center Study.

BACKGROUND: Dynamic contrast-enhanced magnetic resonance imaging is a noninvasive imaging modality that can supply information regarding the tumor anatomy and physiology. The aim of the study was to analyze DCE-MRI perfusion parameters in normal pancreatic parenchymal tissue and PDAC and to evaluate the efficacy of this diagnostic modality in determining the tumor grade. METHODS: A single-center retrospective study was performed. A total of 28 patients with histologically proven PDAC underwent DCE-MRI; the control group enrolled 14 patients with normal pancreatic parenchymal tissue; the radiological findings were compared with histopathological data. The study patients were further grouped according to the differentiation grade (G value): well- and moderately differentiated and poorly differentiated PDAC. RESULTS: The median values of Ktrans, kep and iAUC were calculated lower in PDAC compared with the normal pancreatic parenchymal tissue (p < 0.05). The mean value of Ve was higher in PDAC, compared with the normal pancreatic tissue (p < 0.05). Ktrans, kep and iAUC were lower in poorly differentiated PDAC, whereas Ve showed no differences between groups. CONCLUSIONS: Ve and iAUC DCE-MRI perfusion parameters are important as independent diagnostic criteria predicting the probability of PDAC; the Ktrans and iAUC DCE-MRI perfusion parameters may serve as effective independent prognosticators preoperatively identifying poorly differentiated PDAC.

Surgical strategies for chronic pancreatitis in a 1,327- patient Scandinavian Baltic pancreatic Club (SBPC) register.

BACKGROUND: Chronic pancreatitis (CP) may cause intermittent or continuous pain and complications requiring invasive interventions. No specific recommendations for surgical interventions have been presented. Our aim was to determine the surgical treatment strategies for the treatment of CP in the Scandinavian and Baltic countries. METHODS: This multi-centre cross sectional study included 1327 CP patients from eight centres. The data was gathered from the Scandinavian Baltic Pancreatic Club (SBPC) database. Patients who underwent pancreatic surgery were analysed. The baseline CP population from the eight centres was used as a reference. The information registered included comorbidities, pancreatic function, previous interventions, time and type of surgery and the EORTC-30 quality of life (QOL) questionnaire. RESULTS: Overall, 95/1327 (7%) patients underwent pancreatic surgery. Fifty-one (54%) of these underwent pancreatic surgery for chronic pain (PSCP) and formed the final study group. Median follow-up time was two (range 0-8) years after surgery and seven (1-46) years after diagnosis. The most common surgical procedures were pancreatic resection combined with drainage (54%) followed by pancreatic resections (32%) and drainage procedures (14%). Postoperatively, 47% of the patients were pain free with or without pain medication while 16% had chronic pain episodes, this did not differ from the base CP population. In QOL questionnaires, PSCP patients reported the same QOL but worse social functioning and more symptoms compared to the CP population. CONCLUSIONS: Pancreatic surgery for CP is rare: surgical procedures were performed on only 7% of the CP patients in the SBPC database. In half of the patients the indication was pain. Most of these patients underwent endoscopic procedures before surgery. Half of the patients reported being pain-free after surgery.

Pancreatic enzyme treatment in chronic pancreatitis: Quality of management and adherence to guidelines-A cross-sectional observational study.

OBJECTIVES: Pancreatic exocrine insufficiency (PEI) is a common complication in patients with chronic pancreatitis (CP), leading to increased morbidity and mortality if not treated adequately. Pancreatic enzyme replacement therapy|pancreas enzyme replacement therapy (PERT) is the cornerstone in treatment of patients with PEI. In the present study, we use data from the Scandinavian Baltic Pancreatic Club database to examine adherence of PERT according to United European Gastroenterology evidence-based guidelines treatment of CP. PATIENTS AND METHODS: Patients with definitive or probable CP according to M-ANNHEIM diagnostic criteria were included. We collected information on exposures, exocrine function, intake of pancreatic enzymes, and markers of nutrition. Fecal elastase <200 µg/g was defined as a marker for PEI. Enzyme replacement therapy of 100,000 lipase units or more was defined as adequate treatment. RESULTS: We included 1006 patients from 8 centers in five countries. Sixty-four percent of the patients were correctly treated. Twenty-five per cent of PEI patients were not taking enzymes at all, and 20% of PEI patients were undertreated with insufficient PERT doses according to the guidelines. Fourteen percent of patients with sufficient pancreatic function were receiving enzymes despite normal exocrine pancreatic function. There were center differences. Current smoking was associated with lack of treatment and alcohol abuse was associated with under-treatment. There were no associations between "no treatment" or "under-treatment" for underweight or vitamin D deficiency. CONCLUSION: In our CP expert centers, the adherence to guidelines for enzyme treatment is insufficient. Both patient factors and center differences have influence on treatment adherence.

DNA Methylation of HOXA11 Gene as Prognostic Molecular Marker in Human Gastric Adenocarcinoma.

Hypermethylation of tumor suppressor genes and hypomethylation of oncogenes might be identified as possible biomarkers in gastric cancer (GC). We aimed to assess the DNA methylation status of selected genes in GC tissue samples and evaluate these genes' prognostic importance on patient survival. Patients (99) diagnosed with GC and who underwent gastrectomy were included. We selected a group of genes (RAD51B, GFRA3, AKR7A3, HOXA11, TUSC3, FLI1, SEZ6L, GLDC, NDRG) which may be considered as potential tumor suppressor genes and oncogenes. Methylation of the HOXA11 gene promoter was significantly more frequent in GC tumor tissue (p = 0.006) than in healthy gastric mucosa. The probability of surviving longer (71.2 months (95% CI 57-85.3) vs. 44.3 months (95% CI 34.8-53.9)) was observed with unmethylated HOXA11 promoter in cancer tissues. Survival in patients with a methylation of HOXA11 promoter either in healthy gastric mucosa or gastric cancer tissue was twice as high as in patients with a methylation of HOXA11 promoter in both healthy gastric mucosa and cancer tissue (61.2 months (95% CI 50.9-71.4) vs. 28.5 months (95% CI 20.8-36.2)). Multivariate Cox analysis revealed the HOXA11 methylation as significantly associated with patients' survival (HR = 2.4, 95% CI 1.19-4.86). Our results suggest that the HOXA11 gene might be a potential prognostic molecular marker in patients with gastric adenocarcinoma.

Volume, but Not the Location of Necrosis, Is Associated with Worse Outcomes in Acute Pancreatitis: A Prospective Study.

Background and Objectives: The course and clinical outcomes of acute pancreatitis (AP) are highly variable. Up to 20% of patients develop pancreatic necrosis. Extent and location of it might affect the clinical course and management. The aim was to determine the clinical relevance of the extent and location of pancreatic necrosis in patients with AP. Materials and Methods: A cohort of patients with necrotizing AP was collected from 2012 to 2018 at the Hospital of Lithuanian University of Health Sciences. Patients were allocated to subgroups according to the location (entire pancreas, left and right sides of pancreas) and extent (<30%, 30−50%, >50%) of pancreatic necrosis. Patients were reviewed for demographic features, number of performed surgical interventions, local and systemic complications, hospital stay and mortality rate. All contrast enhanced computed tomography (CECT) scans were evaluated by at least two experienced abdominal radiologists. All patients were treated according to the standard treatment protocol based on current international guidelines. Results: The study included 83 patients (75.9% males (n = 63)) with a mean age of 53 ± 1.7. The volume of pancreatic necrosis exceeded 50% in half of the patients (n = 42, 51%). Positive blood culture (n = 14 (87.5%)), multiple organ dysfunction syndrome (n = 17 (73.9%)) and incidences of respiratory failure (n = 19 (73.1%)) were significantly more often diagnosed in patients with pancreatic necrosis exceeding 50% (p < 0.05). Patients with >50% of necrosis were significantly (p < 0.05) more often diagnosed with moderately severe (n = 24 (41.4%)) and severe (n = 18 (72%)) AP. The number of surgical interventions (n = 18 (72%)) and ultrasound-guided interventions (n = 26 (65%)) was also significantly higher. In patients with whole-pancreas necrosis, incidence of renal insufficiency (n = 11 (64.7%)) and infected pancreatic necrosis (n = 19 (57.6%)) was significantly higher (p < 0.05). Conclusions: The clinical course and outcome were worse in the case of pancreatic necrosis exceeding 50%, rendering the need for longer and more complex treatment.

The essential requirements for an HPB centre to deliver high-quality outcomes.

The concept of a centre approach to the treatment of patients with complex disorders, such as those with hepato-pancreato-biliary (HPB) diseases, is widely applied, although what is needed for an HPB centre to achieve high-quality outcomes remains unclear. We therefore conducted a literature review, which highlighted the paucity of information linking centre structure or process to outcome data outside of caseloads, specialisation, and quality of training. We then conducted an international survey among the largest 107 HPB centres with experts in HPB surgery and found that most responders work in 'virtual' HPB centres without dedicated space, assigned beds, nor personal. We finally analysed our experience with the Swiss HPB centre, previously reported in this journal 15 years ago, disclosing that budget priorities set by the hospital administration may prevent the development of a fully integrated centre, for example through inconsistent assignment of the centre's beds to HBP patients or removal of dedicated intermediate care beds. We propose criteria for essential requirements for an HPB centre to deliver high-quality outcomes, with the concept of "centre of reference" limited to actual, as opposed to virtual, centres.

Correction: Vabalaite et al. Effects of High-Frequency (HF) Repetitive Transcranial Magnetic Stimulation (rTMS) on Upper Extremity Motor Function in Stroke Patients: A Systematic Review. Medicina 2021, 57, 1215.

In the original publication [...].

Pleuropulmonary pathologies in the early phase of acute pancreatitis correlate with disease severity.

BACKGROUND: Respiratory failure worsens the outcome of acute pancreatitis (AP) and underlying factors might be early detectable. AIMS: To evaluate the prevalence and prognostic relevance of early pleuropulmonary pathologies and pre-existing chronic lung diseases (CLD) in AP patients. METHODS: Multicentre retrospective cohort study. Caudal sections of the thorax derived from abdominal contrast enhanced computed tomography (CECT) performed in the early phase of AP were assessed. Independent predictors of severe AP were identified by binary logistic regression analysis. A one-year survival analysis using Kaplan-Meier curves and log rank test was performed. RESULTS: 358 patients were analysed, finding pleuropulmonary pathologies in 81%. CECTs were performed with a median of 2 days (IQR 1-3) after admission. Multivariable analysis identified moderate to severe or bilateral pleural effusions (PEs) (OR = 4.16, 95%CI 2.05-8.45, p<0.001) and pre-existing CLD (OR = 2.93, 95%CI 1.17-7.32, p = 0.022) as independent predictors of severe AP. Log rank test showed a significantly worse one-year survival in patients with bilateral compared to unilateral PEs in a subgroup. CONCLUSIONS: Increasing awareness of the prognostic impact of large and bilateral PEs and pre-existing CLD could facilitate the identification of patients at high risk for severe AP in the early phase and thus improve their prognosis.

Effects of High-Frequency (HF) Repetitive Transcranial Magnetic Stimulation (rTMS) on Upper Extremity Motor Function in Stroke Patients: A Systematic Review.

Background and Objectives: Repetitive transcranial magnetic stimulation (rTMS) is being widely used for treating upper extremity paresis after stroke, however, evidence of applying high-frequency rTMS (HF-rTMS) on the ipsilesional hemisphere for upper extremity motor recovery remains limited. This systematic review aimed to investigate the effect of high-frequency repetitive transcranial magnetic stimulation for upper extremity motor function recovery after a first-time ischaemic stroke. Materials and Methods: This systematic review was prepared according to the preferred reporting items for systematic reviews and meta-analyses (PRISMA) guidelines. A comprehensive literature search was performed to identify all studies published before 12 February 2021. The search was performed on the following databases: PubMed, Ovid, The Cochrane Library. Results: A total of 6440 studies were found in the databases and four trials were included in the review. Three of the studies were randomized control trials (RCT), and one was a pseudo-RCT. Three of the studies showed good methodological quality and one study was rated as excellent. Fugl-Meyer Assessment (FMA) was performed in three out of four studies and the score significantly increased in the HF-rTMS treatment group compared with sham stimulation in all trials. Other measures used in the studies were handgrip strength, shoulder abduction, Motricity Index, Wolf Motor Function Test (WMFT), and Box and Block, although these tests did not show unanimous results. Overall, all four studies conveyed significantly better results in at least one test that was performed for hand motor function evaluation in a 10 Hz stimulation group while none of the tests showed any advantage for sham stimulation groups. Two studies reported headache as an adverse event (six patients in total). Conclusion: The overall results showed that HF-rTMS may increase impaired upper extremity motor function better than sham stimulation in stroke patients.

Transaxillary gasless endoscopic thyroidectomy versus conventional open thyroidectomy: systematic review and meta-analysis.

AIM: This systematic review and meta-analysis evaluates surgical outcome and safety results of conventional (OT) versus endoscopic transaxillary gasless thyroidectomies (ET). MATERIAL AND METHODS: A systematic literature search was performed. The weighted mean differences or the odd ratios with corresponding 95% CIs were examined for surgical outcomes and complications. The results were analysed using fixed- or random-effects models. The heterogeneity was checked by the Cochran Q test and the extent of inconsistency was evaluated by the I2 statistic. RESULTS: Ten studies and 1597 patients were included. All studies found that ET required longer operative time. Postoperative pain was significantly lower after ET on day 1 and day 7. No statistical difference was found in complication rates. CONCLUSIONS: ET has disadvantages such as longer surgery time, but it is a feasible and safe procedure with lower postoperative pain and comparable complication rates to OT. However, good quality prospective randomised studies are necessary to draw firmer conclusions.

Dynamic perfusion CT - A promising tool to diagnose pancreatic ductal adenocarcinoma.

BACKGROUND AND OBJECTIVE: This study deals with an important issue of setting the role and value of the dynamic computed tomography (CT) perfusion analysis in diagnosing pancreatic ductal adenocarcinoma (PDAC). The study aimed to assess the efficacy of perfusion CT in identifying PDAC, even isodense or hardly depicted in conventional multidetector computed tomography. METHODS: A total of 56 patients with PDAC and 56 control group patients were evaluated in this study. A local perfusion assessment, involving the main perfusion parameters, was evaluated for all the patients. Sensitivity, specificity, positive, and negative predictive values for each perfusion CT parameter were defined using cutoff values calculated using receiver operating characteristic curve analysis. We accomplished logistic regression to identify the probability of PDAC. RESULTS: Blood flow (BF) and blood volume (BV) values were significant independent diagnostic criteria for the presence of PDAC. If both values exceed the determined cutoff point, the estimated probability for the presence of PDAC was 97.69%. CONCLUSIONS: Basic CT perfusion parameters are valuable in providing the radiological diagnosis of PDAC. The estimated BF and BV parameters may serve as independent diagnostic criteria predicting the probability of PDAC.

Dynamic Perfusion Computed Tomography and Apparent Diffusion Coefficient as Potential Markers for Poorly Differentiated Pancreatic Adenocarcinoma.

INTRODUCTION: Tumor grade, one of the most important risk factors for survival, is routinely determined after examining the biopsy material or a surgically removed specimen. The aim of the study was to analyze computed tomography (CT) perfusion parameters and diffusion-weighted imaging apparent diffusion coefficient (ADC) values in pancreatic ductal adenocarcinoma (PDAC) and to establish the diagnostic value of these modalities determining the tumor grade. MATERIALS AND METHODS: A prospective clinical study included 56 subjects with PDAC. All the patients had a local perfusion assessment and ADC measurement of the tumor. For the prediction of poor tumor differentiation sensitivity, specificity, positive, and negative predictive values for each perfusion CT and ADC parameters based on cutoff values from ROC analysis were calculated. RESULTS: Mean transit time (MTT) and ADC values were found to be independent prognosticators for the presence of G3 PDAC. MTT and ADC at the cutoff of 17.37 s and 1.15 × 10-3 mm2/s, respectively, appeared to be significant parameters discriminating against the differentiation grade of PDAC. If both values exceeded the defined cutoff point, the estimated probability for the presence of G3 PDAC was 89.29%. CONCLUSION: The MTT parameter, calculated with the deconvolution method, and the ADC value may serve as effective independent prognosticators identifying poorly differentiated PDAC.

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.