Recurrence of idiopathic acute pancreatitis after cholecystectomy: systematic review and meta-analysis

Background: Occult biliary disease has been suggested as a frequent underlying cause of idiopathic acute pancreatitis (IAP). Cholecystectomy has been proposed as a strategy to prevent recurrent IAP. The aim of this systematic review was to determine the efficacy of cholecystectomy in reducing the risk of recurrent IAP. Methods: PubMed, Embase and Cochrane Library databases were searched systematically for studies including patients with IAP treated by cholecystectomy, with data on recurrence of pancreatitis. Studies published before 1980 or including chronic pancreatitis and case reports were excluded. The primary outcome was recurrence rate. Quality was assessed using the Newcastle–Ottawa Scale. Meta-analyses were undertaken to calculate risk ratios using a random-effects model with the inverse-variance method. Results: Overall, ten studies were included, of which nine were used in pooled analyses. The study population consisted of 524 patients with 126 cholecystectomies. Of these 524 patients, 154 (29·4 (95 per cent c.i. 25·5 to 33·3) per cent) had recurrent disease. The recurrence rate was significantly lower after cholecystectomy than after conservative management (14 of 126 (11·1 per cent) versus 140 of 398 (35·2 per cent); risk ratio 0·44, 95 per cent c.i. 0·27 to 0·71). Even in patients in whom IAP was diagnosed after more extensive diagnostic testing, including endoscopic ultrasonography or magnetic resonance cholangiopancreatography, the recurrence rate appeared to be lower after cholecystectomy (4 of 36 (11 per cent) versus 42 of 108 (38·9 per cent); risk ratio 0·41, 0·16 to 1·07). Conclusion: Cholecystectomy after an episode of IAP reduces the risk of recurrent pancreatitis. This implies that current diagnostics are insufficient to exclude a biliary cause

The diagnostic work-up and outcomes of ‘presumed’ idiopathic acute pancreatitis: A post-hoc analysis of a multicentre observational cohort

Introduction: After standard diagnostic work-up, the aetiology of acute pancreatitis remains unknown in 16–27% of cases, a condition referred to as idiopathic acute pancreatitis (IAP). Determining the aetiology of pancreatitis is essential, as it may direct treatment in the acute phase and guides interventions to prevent recurrent pancreatitis. Methods: Between 2008 and 2015, patients with acute pancreatitis were registered prospectively in 19 Dutch hospitals. Patients who had a negative initial diagnostic work-up with regard to the underlying aetiology of their pancreatitis were labelled ‘presumed’ IAP. The aim of this study was to assess the use of diagnostic modalities and their yield to establish an aetiology in ‘presumed’ IAP, and to assess recurrence rates both with and without treatment. Results: Out of the 1632 registered patients, 191 patients had a first episode of ‘presumed’ IAP, of whom 176 (92%) underwent additional diagnostic testing: CT (n = 124, diagnostic yield 8%), EUS (n = 62, yield 35%), MRI/MRCP (n = 56, yield 33%), repeat ultrasound (n = 97, yield 21%), IgG4 (n = 54, yield 9%) and ERCP (n = 15, yield 47%). In 64 of 176 patients (36%) an aetiological diagnosis was established, mostly biliary (n = 39). In 13 out of 176 of patients (7%) a neoplasm was diagnosed. If additional diagnostic workup revealed an aetiology, the recurrence rate was lower in the treated patients than in the patients without a definite aetiology (15% versus 43%, p = 0.014). Conclusion: Additional diagnostic testing revealed an aetiology in one-third of ‘presumed’ IAP patients. The aetiology found was mostly biliary, but occasionally neoplasms were found. Identification of an aetiology with subsequent treatment reduced the rate of recurrence

Fluid hydration to prevent post-ERCP pancreatitis in average- to high-risk patients receiving prophylactic rectal NSAIDs (FLUYT trial): Study protocol for a randomized controlled trial

Background: 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. Methods: 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. Discussion: 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

Impact of nationwide enhanced implementation of best practices in pancreatic cancer care (PACAP-1): A multicenter stepped-wedge cluster randomized controlled trial

Background: Pancreatic cancer has a very poor prognosis. Best practices for the use of chemotherapy, enzyme replacement therapy, and biliary drainage have been identified but their implementation in daily clinical practice is often suboptimal. We hypothesized that a nationwide program to enhance implementation of these best practices in pancreatic cancer care would improve survival and quality of life. Methods/design: PACAP-1 is a nationwide multicenter stepped-wedge cluster randomized controlled superiority trial. In a per-center stepwise and randomized manner, best practices in pancreatic cancer care regarding the use of (neo)adjuvant and palliative chemotherapy, pancreatic enzyme replacement therapy, and metal biliary stents are implemented in all 17 Dutch pancreatic centers and their regional referral networks during a 6-week initiation period. Per pancreatic center, one multidisciplinary team functions as reference for the other centers in the network. Key best practices were identified from the literature, 3 years of data from existing nationwide registries within the Dutch Pancreatic Cancer Project (PACAP), and national expert meetings. The best practices follow the Dutch guideline on pancreatic cancer and the current state of the literature, and can be executed within daily clinical practice. The implementation process includes monitoring, return visits, and provider feedback in combination with education and reminders. Patient outcomes and compliance are monitored within the PACAP registries. Primary outcome is 1-year overall survival (for all disease stages). Secondary outcomes include quality of life, 3- and 5-year overall survival, and guideline compliance. An improvement of 10% in 1-year overall survival is considered clinically relevant. A 25-month study duration was chosen, which provides 80% statistical power for a mortality reduction of 10.0% in the 17 pancreatic cancer centers, with a required sample size of 2142 patients, corresponding to a 6.6% mortality reduction and 4769 patients nationwide. Discussion: The PACAP-1 trial is designed to evaluate whether a nationwide program for enhanced implementation of best practices in pancreatic cancer care can improve 1-year overall survival and quality of life. Trial registration: ClinicalTrials.gov, NCT03513705. Trial opened for accrual on 22th May 2018

Nationwide practice and outcomes of endoscopic biliary drainage in resectable pancreatic head and periampullary cancer

Background: Guidelines advise self-expanding metal stents (SEMS) over plastic stents in preoperative endoscopic biliary drainage (EBD) for malignant extrahepatic biliary obstruction. This study aims to assess nationwide practice and outcomes. Methods: Patients with pancreatic head and periampullary cancer who underwent EBD before pancreatoduodenectomy were included from the Dutch Pancreatic Cancer Audit (2017–2018). Multivariable logistic and linear regression models were performed. Results: In total, 575/1056 patients (62.0%) underwent preoperative EBD: 246 SEMS (42.8%) and 329 plastic stents (57.2%). EBD-related complications were comparable between the groups (44/246 (17.9%) vs. 64/329 (19.5%), p = 0.607), including pancreatitis (22/246 (8.9%) vs. 25/329 (7.6%), p = 0.387). EBD-related cholangitis was reduced after SEMS placement (10/246 (4.1%) vs. 32/329 (9.7%), p = 0.043), which was confirmed in multivariable analysis (OR 0.36 95%CI 0.15–0.87, p = 0.023). Major postoperative complications did not differ (58/246 (23.6%) vs. 90/329 (27.4%), p = 0.316), whereas postoperative pancreatic fistula (24/246 (9.8%) vs. 61/329 (18.5%), p = 0.004; OR 0.50 95%CI 0.27–0.94, p = 0.031) and hospital stay (14.0 days vs. 17.4 days, p = 0.005; B 2.86 95%CI −5.16 to −0.57, p = 0.014) were less after SEMS placement. Conclusion: This study found that preoperative EBD frequently involved plastic stents. SEMS seemed associated with lower risks of cholangitis and less postoperative pancreatic fistula, but without an increased pancreatitis risk

Diagnosis and treatment of pancreatic duct disruption or disconnection: an international expert survey and case vignette study

Background: Pancreatic duct disruption or disconnection is a potentially severe complication of necrotizing pancreatitis. With no existing treatment guidelines, it is unclear whether there is any consensus among experts in clinical practice. We evaluated current expert opinion regarding the diagnosis and treatment of pancreatic duct disruption and disconnection in an international case vignette study. Methods: An online case vignette survey was sent to 110 international expert pancreatologists. Expert selection was based on publications in the last 5 years and/or participation in development of IAP/APA and ESGE guidelines on acute pancreatitis. Consensus was defined as agreement by at least 75% of the experts. Results: The response rate was 51% (n = 56). Forty-four experts (79%) obtained a MRI/MRCP and 52 experts (93%) measured amylase levels in percutaneous drain fluid to evaluate pancreatic duct integrity. The majority of experts favored endoscopic transluminal drainage for infected (peri)pancreatic necrosis and pancreatic duct disruption (84%, n = 45) or disconnection (88%, n = 43). Consensus was lacking regarding the treatment of patients with persistent percutaneous drain production, and with persistent sterile necrosis. Conclusion: This international survey of experts demonstrates that there are many areas for which no consensus existed, providing clear focus for future investigation

Suboptimal care for chronic pancreatitis patients revealed by moderate to low adherence to the United European Gastroenterology evidence-based guidelines (HaPanEU): A Netherlands nationwide analysis

Background and objective: The 2016, United European Gastroenterology evidence-based guidelines for the diagnosis and therapy of chronic pancreatitis (HaPanEU) provided evidence-based recommendations for the management of chronic pancreatitis and allowed for the objective evaluation of the quality of care in several domains of disease management through assessment of guideline adherence. Therefore, the aim of this study is to evaluate the current level and the variety of care for chronic pancreatitis patients in the Netherlands using the HaPanEU guidelines as a reference standard. The majority of these patients were diagnosed before the publication of these guidelines. Therefore, in most patients, the results of the present study with respect to those recommendations regarding the diagnostic process of chronic pancreatitis represent guideline correspondence and not adherence. Methods: A subgroup of patients from the Dutch nationwide chronic pancreatitis registry (CARE) was included in a retrospective cross-sectional observational cohort study. A total of 39 recommendations concerning the non-invasive management of chronic pancreatitis were appointed as quality indicators (QIs). Per patient, the number of relevant QIs was determined and guideline adherence was assessed. Data were analyzed to identify factors associated with guideline adherence. Results: Overall, 97 patients with chronic pancreatitis from 11 hospitals were included. Per patient, a mean number of 26 relevant QIs was applicable, with a

Role of endoscopic ultrasonography in the diagnostic work-up of idiopathic acute pancreatitis (PICUS): study protocol for a nationwide prospective cohort study

INTRODUCTION: Idiopathic acute pancreatitis (IAP) remains a dilemma for physicians as it is uncertain whether patients with IAP may actually have an occult aetiology. It is unclear to what extent additional diagnostic modalities such as endoscopic ultrasonography (EUS) are warranted after a first episode of IAP in order to uncover this aetiology. Failure to timely determine treatable aetiologies delays appropriate treatment and might subsequently cause recurrence of acute pancreatitis. Therefore, the aim of the Pancreatitis of Idiopathic origin: Clinical added value of endoscopic UltraSonography (PICUS) Study is to determine the value of routine EUS in determining the aetiology of pancreatitis in patients with a first episode of IAP. METHODS AND ANALYSIS: PICUS is designed as a multicentre prospective cohort study of 106 patients with a first episode of IAP after complete standard diagnostic work-up, in whom a diagnostic EUS will be performed. Standard diagnostic work-up will include a complete personal and family history, laboratory tests including serum alanine aminotransferase, calcium and triglyceride levels and imaging by transabdominal ultrasound

Accelerometry based assessment of gait parameters in children

The objective of this study was to examine if spatio-temporal gait parameters in healthy children can be determined from accelerations measured at the lower trunk as has been demonstrated in adults, previously. Twenty children aged 3-16 years, participated in a protocol that involved repeated walks of different distances in an indoor environment. During walking, accelerations were measured by three orthogonally mounted acceleration sensors in a small wireless device (DynaPort MiniMod) that was attached to the lower back. Based on an inverted pendulum approach, spatio-temporal gait parameters and walking distances were computed from the acceleration signals. Results were compared to video observations and known walking distances and durations. Steps were successfully detected in 99.6+/-0.6% of all observed steps (n=5554). On average, walking distance was accurately estimated (100.6+/-3.3%, range 93-106.7%). No correlation was found between the number of miscounted steps and the total number of steps or the age of the subject. It can be concluded that the use of an inverted pendulum model provides the possibility to estimate spatio-temporal gait parameters in children as well as in adults. The method allows an inexpensive and comfortable assessment of gait parameters in children, is applicable in controlled, indoor environments and could be tested for applicability under free living conditions