Acute pancreatitis is one of the most common GI conditions requiring acute hospitalisation and has a rising incidence. In recent years, important insights on the management of acute pancreatitis have ...been obtained through numerous randomised controlled trials. Based on this evidence, the treatment of acute pancreatitis has gradually developed towards a tailored, multidisciplinary effort, with distinctive roles for gastroenterologists, radiologists and surgeons. This review summarises how to diagnose, classify and manage patients with acute pancreatitis, emphasising the evidence obtained through randomised controlled trials.
This study systematically explores the prevalence of pancreatic exocrine insufficiency (PEI) after acute pancreatitis in different subgroups of etiology (biliary/alcoholic/other), disease severity ...and follow-up time (<12, 12–36 and > 36 months after index admission).
PubMed and EMBASE databases were searched, 32 studies were included in this study level meta-analysis.
In a total of 1495 patients with acute pancreatitis, tested at a mean of 36 months after index admission, the pooled prevalence of PEI was 27.1% (95%-confidence interval CI: 20.3%–35.1%). Patients from seven studies (n = 194) underwent direct tests with pooled prevalence of 41.7% 18.5%–69.2%. Patients from 26 studies (n = 1305) underwent indirect tests with pooled prevalence of 24.4% 18.3%–31.8%. In subgroup analyses on patients that underwent fecal elastase-1 tests, PEI occurred more often in alcoholic pancreatitis (22.7% 16.6%–30.1%) than in biliary pancreatitis (10.2% 6.2%–16.4%) or other etiology (13.4% 7.7%–22.4%; P = 0.02). Pooled prevalence of PEI after mild and severe pancreatitis was 19.4% 8.6%–38.2% and 33.4% 22.6%–46.3% respectively in studies using fecal elaste-1 tests (P = 0.049). Similar results were seen in patients without (18.9% 9.3%–34.6%) and with necrotizing pancreatitis (32.0% 18.2%–49.8%; P = 0.053). Over time, the prevalence of PEI decreased in patients who underwent the fecal elastase-1 test and increased in patients who underwent the fecal fat analysis.
After acute pancreatitis, a quarter of all patients develop PEI during follow-up. Alcoholic etiology and severe and necrotizing pancreatitis are associated with higher risk of PEI. The prevalence of PEI may change as time of follow-up increases.
Infected necrotizing pancreatitis is a potentially lethal disease that is treated with the use of a step-up approach, with catheter drainage often delayed until the infected necrosis is encapsulated. ...Whether outcomes could be improved by earlier catheter drainage is unknown.
We conducted a multicenter, randomized superiority trial involving patients with infected necrotizing pancreatitis, in which we compared immediate drainage within 24 hours after randomization once infected necrosis was diagnosed with drainage that was postponed until the stage of walled-off necrosis was reached. The primary end point was the score on the Comprehensive Complication Index, which incorporates all complications over the course of 6 months of follow-up.
A total of 104 patients were randomly assigned to immediate drainage (55 patients) or postponed drainage (49 patients). The mean score on the Comprehensive Complication Index (scores range from 0 to 100, with higher scores indicating more severe complications) was 57 in the immediate-drainage group and 58 in the postponed-drainage group (mean difference, -1; 95% confidence interval CI, -12 to 10; P = 0.90). Mortality was 13% in the immediate-drainage group and 10% in the postponed-drainage group (relative risk, 1.25; 95% CI, 0.42 to 3.68). The mean number of interventions (catheter drainage and necrosectomy) was 4.4 in the immediate-drainage group and 2.6 in the postponed-drainage group (mean difference, 1.8; 95% CI, 0.6 to 3.0). In the postponed-drainage group, 19 patients (39%) were treated conservatively with antibiotics and did not require drainage; 17 of these patients survived. The incidence of adverse events was similar in the two groups.
This trial did not show the superiority of immediate drainage over postponed drainage with regard to complications in patients with infected necrotizing pancreatitis. Patients randomly assigned to the postponed-drainage strategy received fewer invasive interventions. (Funded by Fonds NutsOhra and Amsterdam UMC; POINTER ISRCTN Registry number, ISRCTN33682933.).
High-resolution anoscopy is increasingly advocated to screen HIV+ men who have sex with men for anal cancer and its precursor lesions, anal intraepithelial neoplasia. A systematic comparison between ...clinical features and the histopathology of suspect lesions is lacking.
This study aims to analyze interobserver agreement in classifying features of intra-anal lesions suspect for anal intraepithelial neoplasia and to compare these features with their histopathological outcome.
This study is a cross-sectional survey regarding high-resolution anoscopy with images and biopsies of suspect lesions. Two dermatologists experienced in high-resolution anoscopy, blinded for histopathological outcome, independently classified the lesions on clinical features.
This investigation was conducted at the Dermatology outpatient clinic of the Academic Medical Center in Amsterdam, The Netherlands.
Included in the study were 163 HIV+ men who have sex with men, older than 18 years, with no history of anal cancer.
The primary outcomes measured were the κ-coefficient for interobserver agreement and the proportions of anal intraepithelial neoplasia per clinical feature.
Three hundred four biopsies were taken from 163 patients. One hundred sixty-eight biopsies (55%) showed anal intraepithelial neoplasia, and 67/304 (22%) showed high-grade anal intraepithelial neoplasia. The κ-coefficient was 0.65 for condylomatous lesions, 0.14 for surface configuration, 0.54 for punctation, 0.08 for mosaicism, and 0.43 for atypical vessels. Condylomatous lesions showed high-grade anal intraepithelial neoplasia in 18% (95% CI, 11%-27%). In lesions with flat leukoplakia, punctation, and atypical vessels, high-grade anal intraepithelial neoplasia was seen in 25%, 30%, and 23%. In lesions with the combination punctation/atypical vessels and punctation/flat leukoplakia/atypical vessels, high-grade anal intraepithelial neoplasia was found in 38% and 40%.
We did not take biopsies of healthy-looking mucosa. Furthermore, the real-time description of features during high-resolution anoscopy, instead of the use of images, would improve the recognition of subtle mucosal abnormalities.
A moderate to substantial interobserver agreement was demonstrated in recognizing condylomas, punctation, and atypical vessels. Furthermore, high-grade anal intraepithelial neoplasia is present in a high proportion of intra-anal condylomata. A combination of punctation, flat leukoplakia, and atypical vessels is the best predictor for high-grade anal intraepithelial neoplasia.
It remains unclear whether urgent endoscopic retrograde cholangiopancreatography (ERCP) with biliary sphincterotomy improves the outcome of patients with gallstone pancreatitis without concomitant ...cholangitis. We did a randomised trial to compare urgent ERCP with sphincterotomy versus conservative treatment in patients with predicted severe acute gallstone pancreatitis.
In this multicentre, parallel-group, assessor-masked, randomised controlled superiority trial, patients with predicted severe (Acute Physiology and Chronic Health Evaluation II score ≥8, Imrie score ≥3, or C-reactive protein concentration >150 mg/L) gallstone pancreatitis without cholangitis were assessed for eligibility in 26 hospitals in the Netherlands. Patients were randomly assigned (1:1) by a web-based randomisation module with randomly varying block sizes to urgent ERCP with sphincterotomy (within 24 h after hospital presentation) or conservative treatment. The primary endpoint was a composite of mortality or major complications (new-onset persistent organ failure, cholangitis, bacteraemia, pneumonia, pancreatic necrosis, or pancreatic insufficiency) within 6 months of randomisation. Analysis was by intention to treat. This trial is registered with the ISRCTN registry, ISRCTN97372133.
Between Feb 28, 2013, and March 1, 2017, 232 patients were randomly assigned to urgent ERCP with sphincterotomy (n=118) or conservative treatment (n=114). One patient from each group was excluded from the final analysis because of cholangitis (urgent ERCP group) and chronic pancreatitis (conservative treatment group) at admission. The primary endpoint occurred in 45 (38%) of 117 patients in the urgent ERCP group and in 50 (44%) of 113 patients in the conservative treatment group (risk ratio RR 0·87, 95% CI 0·64–1·18; p=0·37). No relevant differences in the individual components of the primary endpoint were recorded between groups, apart from the occurrence of cholangitis (two 2% of 117 in the urgent ERCP group vs 11 10% of 113 in the conservative treatment group; RR 0·18, 95% CI 0·04–0·78; p=0·010). Adverse events were reported in 87 (74%) of 118 patients in the urgent ERCP group versus 91 (80%) of 114 patients in the conservative treatment group.
In patients with predicted severe gallstone pancreatitis but without cholangitis, urgent ERCP with sphincterotomy did not reduce the composite endpoint of major complications or mortality, compared with conservative treatment. Our findings support a conservative strategy in patients with predicted severe acute gallstone pancreatitis with an ERCP indicated only in patients with cholangitis or persistent cholestasis.
The Netherlands Organization for Health Research and Development, Fonds NutsOhra, and the Dutch Patient Organization for Pancreatic Diseases.
Post-endoscopic retrograde cholangiopancreatography (ERCP) pancreatitis (PEP) is the most common complication of ERCP and may run a severe course. Evidence suggests that vigorous periprocedural ...hydration can prevent PEP, but studies to date have significant methodological drawbacks. Importantly, evidence for its added value in patients already receiving prophylactic rectal non-steroidal anti-inflammatory drugs (NSAIDs) is lacking and the cost-effectiveness of the approach has not been investigated. We hypothesize that combination therapy of rectal NSAIDs and periprocedural hydration would significantly lower the incidence of post-ERCP pancreatitis compared to rectal NSAIDs alone in moderate- to high-risk patients undergoing ERCP.
The FLUYT trial is a multicenter, parallel group, open label, superiority randomized controlled trial. A total of 826 moderate- to high-risk patients undergoing ERCP that receive prophylactic rectal NSAIDs will be randomized to a control group (no fluids or normal saline with a maximum of 1.5 mL/kg/h and 3 L/24 h) or intervention group (lactated Ringer's solution with 20 mL/kg over 60 min at start of ERCP, followed by 3 mL/kg/h for 8 h thereafter). The primary endpoint is the incidence of post-ERCP pancreatitis. Secondary endpoints include PEP severity, hydration-related complications, and cost-effectiveness.
The FLUYT trial design, including hydration schedule, fluid type, and sample size, maximize its power of identifying a potential difference in post-ERCP pancreatitis incidence in patients receiving prophylactic rectal NSAIDs.
EudraCT: 2015-000829-37 . Registered on 18 February 2015.
13659155 . Registered on 18 May 2015.
Acute pancreatitis is mostly caused by gallstones or sludge. Early decompression of the biliary tree by endoscopic retrograde cholangiography (ERC) with sphincterotomy may improve outcome in these ...patients. Whereas current guidelines recommend early ERC in patients with concomitant cholangitis, early ERC is not recommended in patients with mild biliary pancreatitis. Evidence on the role of routine early ERC with endoscopic sphincterotomy in patients without cholangitis but with biliary pancreatitis at high risk for complications is lacking. We hypothesize that early ERC with sphincterotomy improves outcome in these patients.
The APEC trial is a randomized controlled, parallel group, superiority multicenter trial. Within 24 hours after presentation to the emergency department, patients with biliary pancreatitis without cholangitis and at high risk for complications, based on an Acute Physiology and Chronic Health Evaluation (APACHE-II) score of 8 or greater, Modified Glasgow score of 3 or greater, or serum C-reactive protein above 150 mg/L, will be randomized. In 27 hospitals of the Dutch Pancreatitis Study Group, 232 patients will be allocated to early ERC with sphincterotomy or to conservative treatment. The primary endpoint is a composite of major complications (that is, organ failure, pancreatic necrosis, pneumonia, bacteremia, cholangitis, pancreatic endocrine, or exocrine insufficiency) or death within 180 days after randomization. Secondary endpoints include ERC-related complications, infected necrotizing pancreatitis, length of hospital stay and an economical evaluation.
The APEC trial investigates whether an early ERC with sphincterotomy reduces the composite endpoint of major complications or death compared with conservative treatment in patients with biliary pancreatitis at high risk of complications.
Current Controlled Trials ISRCTN97372133 (date registration: 17-12-2012).
Pancreatitis is the most common complication of endoscopic retrograde cholangiopancreatography (ERCP). Prophylactic rectal administration of non-steroidal anti-inflammatory drugs (NSAIDs) is ...considered as standard of care to reduce the risk of post-ERCP pancreatitis. It has been suggested that aggressive hydration might further reduce this risk. Guidelines already recommend aggressive hydration in patients who are unable to receive rectal NSAIDs, although it is laborious and time consuming. We aimed to evaluate the added value of aggressive hydration in patients receiving prophylactic rectal NSAIDs.
FLUYT, a multicentre, open-label, randomised, controlled trial done across 22 Dutch hospitals, included patients aged between 18 and 85 years with moderate to high risk of post-ERCP pancreatitis. Patients were randomly assigned (1:1) by a web-based module with varying block sizes to a combination of aggressive hydration and rectal NSAIDs (100 mg diclofenac or indomethacin; aggressive hydration group) or rectal NSAIDs (100 mg diclofenac or indomethacin) alone (control group). Randomisation was stratified according to treatment centre. Aggressive hydration comprised 20 mL/kg intravenous Ringer's lactate solution within 60 min from the start of ERCP, followed by 3 mL/kg per h for 8 h. The control group received normal intravenous saline with a maximum of 1·5 mL/kg per h and 3 L per 24 h. The primary endpoint was post-ERCP pancreatitis and was analysed on a modified intention-to-treat basis (including all patients who underwent randomisation and an ERCP and for whom data regarding the primary outcome were available). The trial is registered with the ISRCTN registry, ISRCTN13659155.
Between June 5, 2015, and June 6, 2019, 826 patients were randomly assigned, of whom 388 in the aggressive hydration group and 425 in the control group were included in the modified intention-to-treat analysis. Post-ERCP pancreatitis occurred in 30 (8%) patients in the aggressive hydration group and in 39 (9%) patients in the control group (relative risk 0·84, 95% CI 0·53-1·33, p=0·53). There were no differences in serious adverse events, including hydration-related complications (relative risk 0·99, 95% CI 0·59-1·64; p=1·00), ERCP-related complications (0·90, 0·62-1·31; p=0·62), intensive care unit admission (0·37, 0·07-1·80; p=0·22), and 30-day mortality (0·95, 0·50-1·83; p=1·00).
Aggressive periprocedural hydration did not reduce the incidence of post-ERCP pancreatitis in patients with moderate to high risk of developing this complication who routinely received prophylactic rectal NSAIDs. Therefore, the burden of laborious and time-consuming aggressive periprocedural hydration to further reduce the risk of post-ERCP pancreatitis is not justified.
Netherlands Organisation for Health Research and Development and Radboud University Medical Center.
Following an episode of acute biliary pancreatitis, cholecystectomy is advised to prevent recurrent biliary events. There is limited evidence regarding the optimal timing and safety of ...cholecystectomy in patients with necrotising biliary pancreatitis.
A post hoc analysis of a multicentre prospective cohort. Patients with biliary pancreatitis and a CT severity score of three or more were included in 27 Dutch hospitals between 2005 and 2014. Primary outcome was the optimal timing of cholecystectomy in patients with necrotising biliary pancreatitis, defined as: the optimal point in time with the lowest risk of recurrent biliary events and the lowest risk of complications of cholecystectomy. Secondary outcomes were the number of recurrent biliary events, periprocedural complications of cholecystectomy and the protective value of endoscopic sphincterotomy for the recurrence of biliary events.
Overall, 248 patients were included in the analysis. Cholecystectomy was performed in 191 patients (77%) at a median of 103 days (P25-P75: 46-222) after discharge. Infected necrosis after cholecystectomy occurred in four (2%) patients with persistent peripancreatic collections. Before cholecystectomy, 66 patients (27%) developed biliary events. The risk of overall recurrent biliary events prior to cholecystectomy was significantly lower before 10 weeks after discharge (risk ratio 0.49 (95% CI 0.27 to 0.90); p=0.02). The risk of recurrent pancreatitis before cholecystectomy was significantly lower before 8 weeks after discharge (risk ratio 0.14 (95% CI 0.02 to 1.0); p=0.02). The complication rate of cholecystectomy did not decrease over time. Endoscopic sphincterotomy did not reduce the risk of recurrent biliary events (OR 1.40 (95% CI 0.74 to 2.83)).
The optimal timing of cholecystectomy after necrotising biliary pancreatitis, in the absence of peripancreatic collections, is within 8 weeks after discharge.
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