Performance of diagnostic tools for acute cholangitis in patients with suspected biliary obstruction

Background: Acute cholangitis is an infection requiring endoscopic retrograde cholangiopancreatography (ERCP) and antibiotics. Several diagnostic tools help to diagnose cholangitis. Because diagnostic performance of these tools has not been studied and might therefore impose unnecessary ERCPs, we aimed to evaluate this. Methods: We established a nationwide prospective cohort of patients with suspected biliary obstruction who underwent an ERCP. We assessed the diagnostic performance of Tokyo Guidelines (TG18), Dutch Pancreatitis Study Group (DPSG) criteria, and Charcot triad relative to real-world cholangitis as the reference standard. Results: 127 (16%) of 794 patients were diagnosed with real-world cholangitis. Using the TG18, DPSG, and Charcot triad, 345 (44%), 55 (7%), and 66 (8%) patients were defined as having cholangitis, respectively. Sensitivity for TG18 was 82% (95% CI 74-88) and specificity 60% (95% CI 56-63). The sensitivity for DPSG and Charcot was 42% (95% CI 33-51) and 46% (95% CI 38-56), specificity was 99.7% (95% CI 99-100) and 99% (95% CI 98-100), respectively. Conclusions: TG18 criteria incorrectly diagnoses four out of ten patients with real-world cholangitis, while DPSG and Charcot criteria failed to diagnose more than half of patients. As the cholangitis diagnosis has many consequences for treatment, there is a need for more accurate diagnostic tools or work-up towards ERCP

Performance of diagnostic tools for acute cholangitis in patients with suspected biliary obstruction

BACKGROUND: Acute cholangitis is an infection requiring endoscopic retrograde cholangiopancreatography (ERCP) and antibiotics. Several diagnostic tools help to diagnose cholangitis. Because diagnostic performance of these tools has not been studied and might therefore impose unnecessary ERCPs, we aimed to evaluate this. METHODS: We established a nationwide prospective cohort of patients with suspected biliary obstruction who underwent an ERCP. We assessed the diagnostic performance of Tokyo Guidelines (TG18), Dutch Pancreatitis Study Group (DPSG) criteria, and Charcot triad relative to real-world cholangitis as the reference standard. RESULTS: 127 (16%) of 794 patients were diagnosed with real-world cholangitis. Using the TG18, DPSG, and Charcot triad, 345 (44%), 55 (7%), and 66 (8%) patients were defined as having cholangitis, respectively. Sensitivity for TG18 was 82% (95% CI 74-88) and specificity 60% (95% CI 56-63). The sensitivity for DPSG and Charcot was 42% (95% CI 33-51) and 46% (95% CI 38-56), specificity was 99.7% (95% CI 99-100) and 99% (95% CI 98-100), respectively. CONCLUSIONS: TG18 criteria incorrectly diagnoses four out of ten patients with real-world cholangitis, while DPSG and Charcot criteria failed to diagnose more than half of patients. As the cholangitis diagnosis has many consequences for treatment, there is a need for more accurate diagnostic tools or work-up towards ERCP

Suspected common bile duct stones: reduction of unnecessary ERCP by pre-procedural imaging and timing of ERCP

Background: Endoscopic retrograde cholangiopancreatography (ERCP) is the procedure of choice to remove sludge/stones from the common bile duct (CBD). In a small but clinically important proportion of patients with suspected choledocholithiasis ERCP is negative. This is undesirable because of ERCP associated morbidity. We aimed to map the diagnostic pathway leading up to ERCP and evaluate ERCP outcome. Methods: We established a prospective multicenter cohort of patients with suspected CBD stones. We assessed the determinants that were associated with CBD sludge or stone detection upon ERCP. Results: We established a cohort of 707 patients with suspected CBD sludge or stones (62% female, median age 59 years). ERCP was negative for CBD sludge or stones in 155 patients (22%). Patients with positive ERCPs frequently had pre-procedural endoscopic ultrasonography (EUS) or magnetic resonance cholangiopancreatography (MRCP) imaging (44% vs. 35%; P = 0.045). The likelihood of ERCP sludge and stones detection was higher when the time interval between EUS or MRCP and ERCP was less than 2 days (odds ratio 2.35; 95% CI 1.25–4.44; P = 0.008; number needed to harm 7.7). Conclusions: Even in the current era of society guidelines and use of advanced imaging CBD sludge or stones are absent in one out of five ERCPs performed for suspected CBD stones. The proportion of unnecessary ERCPs is lower in case of pre-procedural EUS or MRCP. A shorter time interval between EUS or MRCP increases the yield of ERCP for suspected CBD stones and should, therefore, preferably be performed within 2 days before ERCP. Graphical abstract: [Figure not available: see fulltext.]

Perforation and Fistula of the Gastrointestinal Tract in Patients with Necrotizing Pancreatitis: a Nationwide Prospective Cohort

OBJECTIVE: The aim of this study was to explore the incidence, risk factors, clinical course and treatment of perforation and fistula of the gastrointestinal tract in a large unselected cohort of patients with necrotizing pancreatitis. SUMMARY BACKGROUND DATA: Perforation and fistula of the gastrointestinal (GI)-tract may occur in necrotizing pancreatitis. Data from large unselected patient populations on the incidence, risk factors, clinical outcomes, and treatment are lacking. METHODS: We performed a post-hoc analysis of a nationwide prospective database of 896 patients with necrotizing pancreatitis. GI-tract perforation and fistula were defined as spontaneous or iatrogenic discontinuation of the gastrointestinal wall. Multivariable logistic regression was used to explore risk factors and to adjust for confounders to explore associations of the GI-tract perforation and fistula on the clinical course. RESULTS: A perforation or fistula of the GI-tract was identified in 139 (16%) patients, located in the stomach in 23 (14%), duodenum in 56 (35%), jejunum or ileum in 18 (11%) and colon in 64 (40%). Risk factors were high C-reactive protein within 48-hours after admission (OR 1.19 [95%CI 1.01-1.39]) and early organ-failure (OR 2.76 [95%CI 1.78-4.29]). Prior invasive intervention was a risk factor for developing a perforation or fistula of the lower GI-tract (OR 2.60 [95% CI 1.04-6.60]). While perforation or fistula of the upper GI-tract appeared to be protective for persistent ICU-admission (OR 0.11 [95%CI 0.02-0.44]) and persistent organ failure (OR 0.15 [95%CI 0.02-0.58]), perforation or fistula of the lower GI-tract was associated with a higher rate of new onset organ failure (OR 2.47 [95%CI 1.23-4.84]). When the stomach or duodenum was affected, treatment was mostly conservative (n=54, 68%). Treatment was mostly surgical when the colon was affected (n=38, 59%). CONCLUSIONS: Perforation and fistula of the GI-tract occurred in one out of six patients with necrotizing pancreatitis. Risk factors were high C-reactive protein within 48 hours and early organ-failure. Prior intervention was identified as a risk factor for perforation or fistula of the lower GI-tract. The clinical course was mostly affected by involvement of the lower GI-tract

Aggressive fluid hydration plus non-steroidal anti-inflammatory drugs versus non-steroidal anti-inflammatory drugs alone for post-endoscopic retrograde cholangiopancreatography pancreatitis (FLUYT): a multicentre, open-label, randomised, controlled trial

Background: 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. Methods: 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. Findings: 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). Interpretation: 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. Funding: Netherlands Organisation for Health Research and Development and Radboud University Medical Center

Over- and Misuse of Antibiotics and the Clinical Consequence in Necrotizing Pancreatitis:An Observational Multicenter Study

OBJECTIVE: The use and impact of antibiotics and the impact of causative pathogens on clinical outcomes in a large real-world cohort covering the entire clinical spectrum of necrotizing pancreatitis remain unknown. SUMMARY BACKGROUND DATA: International guidelines recommend broad-spectrum antibiotics in patients with suspected infected necrotizing pancreatitis. This recommendation is not based on high-level evidence and clinical effects are unknown. METHODS: This study is a post-hoc analysis of a nationwide prospective cohort of 401 patients with necrotizing pancreatitis in 15 Dutch centers (2010-2019). Across the patient population from time of admission to 6 months post admission, multivariable regression analyses were used to analyze (1) microbiological cultures and (2) the antibiotic use. RESULTS: Antibiotics were started in 321/401 patients (80%) administered at a median of 5 days (P25-P75: 1-13) after admission. Median duration of antibiotics was 27 days (P25-P75: 15-48). In 221/321 patients (69%) infection was not proven by cultures at time of initiation of antibiotics. Empirical antibiotics for infected necrosis provided insufficient coverage in 64/128 patients (50%) with a pancreatic culture. Prolonged antibiotic therapy was associated with Enterococcus infection (OR1.08 [95%CI 1.03-1.16], P=0.01). Enterococcus infection was associated with new/persistent organ failure (OR3.08 [95%CI 1.35-7.29], P<0.01) and mortality (OR5.78 [95% CI 1.46-38.73], P=0.03). Yeast were found in 30/147 cultures (20%). DISCUSSION: In this nationwide study of patients with necrotizing pancreatitis, the vast majority received antibiotics, typically administered early in the disease course and without a proven infection. Empirical antibiotics were inappropriate based on pancreatic cultures in half the patients. Future clinical research and practice must consider antibiotic selective pressure due to prolonged therapy, coverage of Enterococcus and yeast. Improved guidelines on antimicrobial diagnostics and therapy could reduce inappropriate antibiotic use and improve clinical outcomes

Short- and long-term outcomes of a disruption and disconnection of the pancreatic duct in necrotizing pancreatitis: a multicenter cohort study in 896 patients : Disrupted pancreatic duct in acute pancreatitis

OBJECTIVES: Necrotizing pancreatitis may result in a disrupted or disconnected pancreatic duct (DPD) with the potential for long lasting negative impact on a patient's clinical outcome. There is a lack of detailed data on the full clinical spectrum of DPD which is critical for the development of better diagnostic and treatment strategies. METHODS: We performed a long-term post-hoc analysis of a prospectively collected nationwide cohort of 896 patients with necrotizing pancreatitis (2005-2015). The median follow-up after hospital admission was 75 months (P25-P75:41-151). Clinical outcomes of patients with and without DPD were compared using regression analyses, adjusted for potential confounders. Predictive features for DPD were explored. RESULTS: DPD was confirmed in 243 (27%) of the 896 patients and resulted in worse clinical outcomes during both the patient's initial admission and follow-up. During hospital admission, DPD was associated with an increased rate of new-onset intensive care unit admission (adjusted-OR2.52 [95%-CI 1.62-3.93]), new-onset organ failure (adjusted-OR2.26 [95%-CI 1.45-3.55]), infected necrosis (adjusted-OR4.63 [95%-CI 2.87-7.64]) and pancreatic interventions (adjusted-OR7.55 [95%-CI 4.23-13.96]). During long-term follow-up, DPD increased the risk of pancreatic intervention (adjusted-OR9.71 [95%-CI 5.37-18.30], recurrent pancreatitis (adjusted-OR2.08 [95%-CI 1.32-3.29]), chronic pancreatitis (adjusted-OR2.73 [95%-CI 1.47-5.15]) and endocrine pancreatic insufficiency (adjusted-OR1.63 [95%-CI 1.05-2.53]).Central or subtotal pancreatic necrosis on computed tomography (CT), (OR9.49 [95%-CI 6.31-14.29] and a high levels of serum C-reactive protein (CRP) in the first 48 hours after admission (per 10 points increase, OR1.02 [95%-CI 1.00-1.03] were identified as independent predictors for developing DPD. CONCLUSIONS: At least one of every four patients with necrotizing pancreatitis suffer from DPD which is associated with detrimental, short and long-term interventions and complications. Central and subtotal pancreatic necrosis and high levels of serum CRP in the first 48 hours are independent predictors for DPD

Comparison of lumen-apposing metal stents versus double-pigtail plastic stents for infected necrotising pancreatitis

Objective Lumen-apposing metal stents (LAMS) are believed to clinically improve endoscopic transluminal drainage of infected necrosis when compared with double-pigtail plastic stents. However, comparative data from prospective studies are very limited. Design Patients with infected necrotising pancreatitis, who underwent an endoscopic step-up approach with LAMS within a multicentre prospective cohort study were compared with the data of 51 patients in the randomised TENSION trial who had been assigned to the endoscopic step-up approach with double-pigtail plastic stents. The clinical study protocol was otherwise identical for both groups. Primary end point was the need for endoscopic transluminal necrosectomy. Secondary end points included mortality, major complications, hospital stay and healthcare costs. Results A total of 53 patients were treated with LAMS in 16 hospitals during 27 months. The need for endoscopic transluminal necrosectomy was 64% (n=34) and was not different from the previous trial using plastic stents (53%, n=27)), also after correction for baseline characteristics (OR 1.21 (95% CI 0.45 to 3.23)). Secondary end points did not differ between groups either, which also included bleeding requiring intervention-5 patients (9%) after LAMS placement vs 11 patients (22%) after placement of plastic stents (relative risk 0.44; 95% CI 0.16 to 1.17). Total healthcare costs were also comparable (mean difference -euro6348, bias-corrected and accelerated 95% CI -euro26 386 to euro10 121). Conclusion Our comparison of two patient groups from two multicentre prospective studies with a similar design suggests that LAMS do not reduce the need for endoscopic transluminal necrosectomy when compared with double-pigtail plastic stents in patients with infected necrotising pancreatitis. Also, the rate of bleeding complications was comparable

Comparison of lumen-apposing metal stents versus double-pigtail plastic stents for infected necrotising pancreatitis

Objective: Lumen-apposing metal stents (LAMS) are believed to clinically improve endoscopic transluminal drainage of infected necrosis when compared with double-pigtail plastic stents. However, comparative data from prospective studies are very limited. Design: Patients with infected necrotising pancreatitis, who underwent an endoscopic step-up approach with LAMS within a multicentre prospective cohort study were compared with the data of 51 patients in the randomised TENSION trial who had been assigned to the endoscopic step-up approach with double-pigtail plastic stents. The clinical study protocol was otherwise identical for both groups. Primary end point was the need for endoscopic transluminal necrosectomy. Secondary end points included mortality, major complications, hospital stay and healthcare costs. Results: A total of 53 patients were treated with LAMS in 16 hospitals during 27 months. The need for endoscopic transluminal necrosectomy was 64% (n=34) and was not different from the previous trial using plastic stents (53%, n=27)), also after correction for baseline characteristics (OR 1.21 (95% CI 0.45 to 3.23)). Secondary end points did not differ between groups either, which also included bleeding requiring intervention - 5 patients (9%) after LAMS placement vs 11 patients (22%) after placement of plastic stents (relative risk 0.44; 95% CI 0.16 to 1.17). Total healthcare costs were also comparable (mean difference -€6348, bias-corrected and accelerated 95% CI -€26 386 to €10 121). Conclusion: Our comparison of two patient groups from two multicentre prospective studies with a similar design suggests that LAMS do not reduce the need for endoscopic transluminal necrosectomy when compared with double-pigtail plastic stents in patients with infected necrotising pancreatitis. Also, the rate of bleeding complications was comparable

Comparison of lumen-apposing metal stents versus double-pigtail plastic stents for infected necrotising pancreatitis

Objective: Lumen-apposing metal stents (LAMS) are believed to clinically improve endoscopic transluminal drainage of infected necrosis when compared with double-pigtail plastic stents. However, comparative data from prospective studies are very limited. Design: Patients with infected necrotising pancreatitis, who underwent an endoscopic step-up approach with LAMS within a multicentre prospective cohort study were compared with the data of 51 patients in the randomised TENSION trial who had been assigned to the endoscopic step-up approach with double-pigtail plastic stents. The clinical study protocol was otherwise identical for both groups. Primary end point was the need for endoscopic transluminal necrosectomy. Secondary end points included mortality, major complications, hospital stay and healthcare costs. Results: A total of 53 patients were treated with LAMS in 16 hospitals during 27 months. The need for endoscopic transluminal necrosectomy was 64% (n=34) and was not different from the previous trial using plastic stents (53%, n=27)), also after correction for baseline characteristics (OR 1.21 (95% CI 0.45 to 3.23)). Secondary end points did not differ between groups either, which also included bleeding requiring intervention - 5 patients (9%) after LAMS placement vs 11 patients (22%) after placement of plastic stents (relative risk 0.44; 95% CI 0.16 to 1.17). Total healthcare costs were also comparable (mean difference -€6348, bias-corrected and accelerated 95% CI -€26 386 to €10 121). Conclusion: Our comparison of two patient groups from two multicentre prospective studies with a similar design suggests that LAMS do not reduce the need for endoscopic transluminal necrosectomy when compared with double-pigtail plastic stents in patients with infected necrotising pancreatitis. Also, the rate of bleeding complications was comparable