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Swaminathan G, Lin YC, Ni J, Khalid A, Tsai CY, Ding Y, Bo N, Murayi JA, Jayaraman T, Poropatich R, Bottino R, Papachristou GI, Sheth SG, Wen L, Barakat MT, Frymoyer AR, Yu M, Husain SZ. Why is the rectal route for NSAIDS favorable for preventing post-ERCP pancreatitis? Pancreatology 2025:S1424-3903(25)00032-8. [PMID: 39922728 DOI: 10.1016/j.pan.2025.02.004] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/04/2024] [Revised: 01/22/2025] [Accepted: 02/04/2025] [Indexed: 02/10/2025]
Abstract
OBJECTIVE Acute pancreatitis is a frequent, burdensome adverse event of endoscopic retrograde cholangiography (ERCP). Rectal nonsteroidal anti-inflammatory drugs (NSAIDs) have reduced post-ERCP pancreatitis (PEP) risk by about 50 % and show greater efficacy over parenteral or oral administration, although the mechanism for its superiority remains unclear. To probe this question, we investigated in a preclinical model, the pharmacokinetics in the blood, pancreas and other tissues of the NSAID diclofenac given via the rectal, intravenous, or intragastric routes. METHODS The data on diclofenac was extracted from a larger study that examined a combination of diclofenac and tacrolimus. 20.8 mg diclofenac/kg body weight, which is the mouse equivalent dosing used in clinical practice for PEP prophylaxis, was administered to C57BL/6J mice via the rectal, intravenous and intragastric (oral) routes. Cross-collection of blood and tissues was done at various timepoints after administration for the evaluation of drug levels and pharmacokinetic parameters. RESULTS Rectal diclofenac demonstrated favorable blood pharmacokinetics and systemic bioavailability as well as sustained pancreas penetration. The total pancreas exposure to diclofenac over 24 h following rectal dosing was not significantly different as compared to intravenous and oral dosing. CONCLUSION Our findings suggest that the efficacy of rectal diclofenac in PEP prevention relates more to its higher and consistent systemic exposure than its absolute pancreas levels. The implications are that the rectal route provides both systemic and pancreas exposure for the full duration of PEP vulnerability.
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Affiliation(s)
- Gayathri Swaminathan
- Division of Gastroenterology, Hepatology and Nutrition, Department of Pediatrics, Stanford University, School of Medicine, Stanford, CA, USA
| | - Yu-Chu Lin
- Division of Gastroenterology, Hepatology and Nutrition, Department of Pediatrics, Stanford University, School of Medicine, Stanford, CA, USA
| | - Jianbo Ni
- Division of Gastroenterology, Hepatology and Nutrition, Department of Pediatrics, Stanford University, School of Medicine, Stanford, CA, USA; Department of Gastroenterology and Shanghai Key Laboratory of Pancreatic Disease, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Asna Khalid
- Division of Gastroenterology, Hepatology and Nutrition, Department of Pediatrics, Stanford University, School of Medicine, Stanford, CA, USA
| | - Cheng-Yu Tsai
- Division of Gastroenterology, Hepatology and Nutrition, Department of Pediatrics, Stanford University, School of Medicine, Stanford, CA, USA
| | - Ying Ding
- Department of Biostatistics, University of Pittsburgh, Pittsburgh, PA, USA
| | - Na Bo
- Department of Biostatistics, University of Pittsburgh, Pittsburgh, PA, USA
| | - Judy-April Murayi
- Division of Gastroenterology, Hepatology, and Nutrition, Department of Pediatrics, Nationwide Children's Hospital, Columbus, OH, USA
| | - Thottala Jayaraman
- Department of Oral and Craniofacial Sciences, School of Dental Medicine, McGowan Institute for Regenerative Medicine, University of Pittsburgh, Pittsburgh, PA, USA
| | | | - Rita Bottino
- Imagine Islet Center, Imagine Pharma, 1401 Forbes Avenue, Pittsburgh, PA, USA
| | | | - Sunil G Sheth
- Beth Israel Deaconess Medical Center, Boston, MA, USA
| | - Li Wen
- Institute of Clinical Medicine, Peking Union Medical College Hospital, Chinese Academy of Medical Science & Peking Union Medical College, Beijing, China
| | - Monique T Barakat
- Division of Gastroenterology, Hepatology and Nutrition, Department of Pediatrics, Stanford University, School of Medicine, Stanford, CA, USA; Division of Gastroenterology and Hepatology, Department of Medicine, Stanford University School of Medicine, Stanford, CA, USA
| | - Adam R Frymoyer
- Division of Neonatology, Department of Pediatrics, Stanford University School of Medicine, Stanford, CA, USA
| | - Mang Yu
- Division of Gastroenterology, Hepatology and Nutrition, Department of Pediatrics, Stanford University, School of Medicine, Stanford, CA, USA.
| | - Sohail Z Husain
- Division of Gastroenterology, Hepatology and Nutrition, Department of Pediatrics, Stanford University, School of Medicine, Stanford, CA, USA.
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Hamo-Giladi DB, Fokra A, Sabo E, Kabala A, Minkov I, Hamoud S, Hadad S, Abassi Z, Khamaysi I. Involvement of heparanase in the pathogenesis of acute pancreatitis: Implication of novel therapeutic approaches. J Cell Mol Med 2024; 28:e18512. [PMID: 39248454 PMCID: PMC11382361 DOI: 10.1111/jcmm.18512] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/02/2023] [Revised: 06/07/2024] [Accepted: 06/18/2024] [Indexed: 09/10/2024] Open
Abstract
Acute pancreatitis (AP) is a common gastrointestinal disease with high morbidity and mortality rate. Unfortunately, neither the etiology nor the pathophysiology of AP are fully understood and causal treatment options are not available. Recently we demonstrated that heparanase (Hpa) is adversely involved in the pathogenesis of AP and inhibition of this enzyme ameliorates the manifestation of the disease. Moreover, a pioneer study demonstrated that Aspirin has partial inhibitory effect on Hpa. Another compound, which possesses a mild pancreato-protective effect against AP, is Trehalose, a common disaccharide. We hypothesized that combination of Aspirin, Trehalose, PG545 (Pixatimod) and SST0001 (Roneparstat), specific inhibitors of Hpa, may exert pancreato-protective effect better than each drug alone. Thus, the current study examines the pancreato-protective effects of Aspirin, Trehalose, PG545 and SST0001 in experimental model of AP induced by cerulein in wild-type (WT) and Hpa over-expressing (Hpa-Tg) mice. Cerulein-induced AP in WT mice was associated with significant rises in the serum levels of lipase (X4) and amylase (X3) with enhancement of pancreatic edema index, inflammatory response, and autophagy. Responses to cerulein were all more profound in Hpa-Tg mice versus WT mice, evident by X7 and X5 folds increase in lipase and amylase levels, respectively. Treatment with Aspirin or Trehalose alone and even more so in combination with PG545 or SST0001 were highly effective, restoring the serum level of lipase back to the basal level. Importantly, a novel newly synthesized compound termed Aspirlose effectively ameliorated the pathogenesis of AP as a single agent. Collectively, the results strongly indicate that targeting Hpa by using anti-Hpa drug combinations constitute a novel therapy for this common orphan disease.
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Affiliation(s)
- Dalit B Hamo-Giladi
- Department of Physiology, The Ruth & Bruce Rappaport Faculty of Medicine, Haifa, Israel
| | - Ahmad Fokra
- Department of Physiology, The Ruth & Bruce Rappaport Faculty of Medicine, Haifa, Israel
| | - Edmond Sabo
- Department of Pathology, Carmel Hospital, Haifa, Israel
| | - Aviva Kabala
- Department of Physiology, The Ruth & Bruce Rappaport Faculty of Medicine, Haifa, Israel
| | - Irena Minkov
- Department of Pathology, Rambam Health Care Center, Haifa, Israel
| | - Shadi Hamoud
- Department of Internal Medicine E, Rambam Health Care Center, Haifa, Israel
| | - Salim Hadad
- Department of Pharmacy, Rambam Health Care Center, Haifa, Israel
| | - Zaid Abassi
- Department of Physiology, The Ruth & Bruce Rappaport Faculty of Medicine, Haifa, Israel
- Department of Laboratory Medicine, Rambam Health Care Center, Haifa, Israel
| | - Iyad Khamaysi
- Department of Gastroenterology, Rambam Health Care Center, Haifa, Israel
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Inamdar S, Cote GA, Yadav D. Endotherapy for Pancreas Divisum. Gastrointest Endosc Clin N Am 2023; 33:789-805. [PMID: 37709411 DOI: 10.1016/j.giec.2023.04.012] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 09/16/2023]
Abstract
Pancreas divisum (PD) is a common anatomic variant of the pancreatic duct. Causal association between PD and pancreatitis has been debated for many years. Minor papilla sphincterotomy (miES) is offered in clinical practice to patients with idiopathic acute recurrent pancreatitis (iRAP) and PD. However, available data originate mainly from observational studies with many limitations. An ongoing international, multicenter, sham-controlled trial is evaluating the efficacy of miES in iRAP and PD. Endoscopic therapy for pain relief has limited to no benefit in patients with chronic abdominal pain or chronic pancreatitis who have PD and is not recommended.
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Affiliation(s)
- Sumant Inamdar
- Division of Gastroenterology and Hepatology, Department of Medicine, University of Arkansas for Medical Sciences, Shorey Building, 8th Floor, 4301 West Markham Street, Little Rock, AR 72205, USA.
| | - Gregory A Cote
- Division of Gastroenterology, Oregon Health and Science University, 3181 SW Sam Jackson Park Road, Mail Code L461, Portland, OR, USA
| | - Dhiraj Yadav
- Division of Gastroenterology, Hepatology and Nutrition, University of Pittsburg Medical Center, 200 Lothrop Street, M2, C-wing, Pittsburgh, PA 15213, USA
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An Insight on Pharmacological and Mechanical Preventive Measures of Post-ERCP PANCREATITIS (PEP)—A Review. GASTROENTEROLOGY INSIGHTS 2022. [DOI: 10.3390/gastroent13040038] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/12/2022] Open
Abstract
Pancreatitis is the most common complication following endoscopic retrograde cholangio-pancreatography (ERCP). With the progress of research in many drugs and technologies, promising efficacy has been achieved in preventing post-ERCP pancreatitis (PEP). Recently, combined prevention has received more attention in order to further reduce the incidence of PEP. However, there is no review about the combined prevention of PEP. This review summarizes the medication and ERCP techniques that are used to prevent PEP and emphasizes that appropriate combination prevention approaches should be based on risk stratification.
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Pin F, Conti Bellocchi MC, Crinò SF, Bernardoni L, Facciorusso A, Gabbrielli A. Double guide-wire technique versus transpancreatic biliary sphincterotomy for difficult biliary cannulation: Real life experience from a referral center. Dig Liver Dis 2022; 54:1548-1553. [PMID: 35931625 DOI: 10.1016/j.dld.2022.07.011] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/20/2022] [Accepted: 07/19/2022] [Indexed: 12/30/2022]
Abstract
BACKGROUND During ERCP for biliary indication, when a difficult bile duct (BD) cannulation occurs, with unintended access to the main pancreatic duct (PD), both double guidewire technique (DGW) and transpancreatic biliary sphincterotomy (TPBS) can be performed. We aimed to compare the technical success and adverse events (AEs) rate of these techniques. METHODS A retrospective analysis of patients with naïve papillae referred to the Pancreas Institute of Verona from January 2016 and July 2021 to undergo ERCP for biliary indications was performed. RESULTS Overall, 202 patients (53.5% males, mean age 67.2 years) were evaluated (96 DGW, 106 TPBS). Malignant biliary stricture was the most common ERCP indication (78.2%). The rate of success in deep biliary cannulation was significantly higher in the DGW group (94.8%) compared to TPBS (79.2%) at the first attempt (p = 0.001). This result was also confirmed in the subgroup of patients with malignant distal stricture (72/77, 93.5% vs 63/80, 78.8%, p = 0.01). No significant difference in AEs rate, particularly in PEP incidence was found between the two groups. CONCLUSIONS DGW demonstrated a higher success rate and similar safety profile compared with TPBS in difficult biliary cannulation. Based on this retrospective study, DGW should be preferred over TPBS in case of unintended PD cannulation. Further prospective studies are needed to confirm our results.
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Affiliation(s)
- Federico Pin
- Diagnostic and interventional Endoscopy of Pancreas, Pancreas Institute, University of Verona, Italy
| | | | - Stefano Francesco Crinò
- Diagnostic and interventional Endoscopy of Pancreas, Pancreas Institute, University of Verona, Italy
| | - Laura Bernardoni
- Diagnostic and interventional Endoscopy of Pancreas, Pancreas Institute, University of Verona, Italy
| | - Antonio Facciorusso
- Digestive Endoscopy Unit, Department of Medical Sciences, University of Foggia, Foggia, Italy
| | - Armando Gabbrielli
- Diagnostic and interventional Endoscopy of Pancreas, Pancreas Institute, University of Verona, Italy
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Dietrich CF, Bekkali NL, Burmeister S, Dong Y, Everett SM, Hocke M, Ignee A, On W, Hebbar S, Oppong K, Sun S, Jenssen C, Braden B. Controversies in ERCP: Indications and preparation. Endosc Ultrasound 2022; 11:186-200. [PMID: 34677145 PMCID: PMC9258020 DOI: 10.4103/eus-d-21-00106] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/10/2021] [Accepted: 07/13/2021] [Indexed: 11/29/2022] Open
Abstract
The aim of the series of papers on controversies of biliopancreatic drainage procedures is to discuss the pros and cons of the varying clinical practices and techniques in ERCP and EUS for drainage of biliary and pancreatic ducts. The first part focuses on indications, clinical and imaging prerequisites before ERCP, sedation options, post-ERCP pancreatitis (PEP) prophylaxis, and other related technical topics. In the second part, specific procedural ERCP-techniques including precut techniques and its timing as well as management algorithms are discussed. In addition, controversies in EUS-guided bile duct and pancreatic drainage procedures are under preparation.
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Affiliation(s)
- Christoph F. Dietrich
- Department of Ultrasound, The First Affiliated Hospital of Zhengzhou University, China
- Johann Wolfgang Goethe University, Frankfurt/Main, Germany
- Department of Allgemeine Innere Medizin, Kliniken Hirslanden Beau Site, Salem und Permanence, Bern, Switzerland
| | - Noor L. Bekkali
- Translational Gastroenterology Unit, Oxford University Hospitals NHS Foundation Trust, Oxford, United Kingdom
| | - Sean Burmeister
- Surgical Gastroenterology Unit, Groote Schuur Hospital, Cape Town, South Africa
| | - Yi Dong
- Department of Ultrasound, Zhongshan Hospital, Fudan University, Shanghai, China
| | | | - Michael Hocke
- Medical Department, Helios Klinikum Meiningen, Meiningen, Germany
| | - Andre Ignee
- Medical Department 2, Caritas-Krankenhaus, Uhlandstr 7, D-97980 Bad Mergentheim, Germany
| | - Wei On
- Leeds Teaching Hospitals NHS Trust, Leeds, United Kingdom
| | - Srisha Hebbar
- University Hospitals of North Midlands, North Midlands, United Kingdom
| | - Kofi Oppong
- HPB Unit, Freeman Hospital, Newcastle upon Tyne, United Kingdom
| | - Siyu Sun
- Endoscopy Center, Sheng Jing Hospital of China Medical University, Shenyang, Liaoning, China
| | - Christian Jenssen
- Department of Internal Medicine, Krankenhaus Märkisch-Oderland, Strausberg, Germany
- Brandenburg Institute for Clinical Ultrasound at Medical University Brandenburg, Neuruppin, Germany
| | - Barbara Braden
- Translational Gastroenterology Unit, Oxford University Hospitals NHS Foundation Trust, Oxford, United Kingdom
- Johann Wolfgang Goethe University, Frankfurt/Main, Germany
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An Open-Label Randomized Controlled Trial Comparing Effectiveness of Aggressive Hydration Versus High-dose Rectal Indomethacin in the Prevention of Postendoscopic Retrograde Cholangiopancreatographic Pancreatitis (AHRI-PEP). J Clin Gastroenterol 2022; 57:524-530. [PMID: 35470300 DOI: 10.1097/mcg.0000000000001712] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/31/2021] [Accepted: 03/18/2022] [Indexed: 12/10/2022]
Abstract
BACKGROUND Although rectal administration of nonsteroidal anti-inflammatory drugs is recommended as the standard pharmacologic modality to prevent postendoscopic retrograde cholangiopancreatography (ERCP) post-ERCP pancreatitis (PEP), vigorous periprocedural hydration (vHR) with lactated Ringer's solution (LR) is emerging as an effective prophylaxis modality for PEP. There has been no head-to-head comparison between these 2. STUDY This was a single-center, randomized, open-label, noninferiority, parallel-assigned, equal allocation, controlled clinical trial in a tertiary care hospital. Consecutive adults referred for ERCP, satisfying predefined inclusion criteria, underwent simple randomization and blinded allocation into 2 groups. Those allocated to vHR received intravenous LR at 3 mL/kg/h during procedure, 20 ml/kg bolus immediately afterward, and then at 3 mL/kg/h for another 8 hours. Those randomized to rectal Indomethacin received only per-rectal 100 mg suppository immediately post-ERCP. Assuming PEP of 9% in Indomethacin arm and noninferiority margin of 4%, we calculated sample size of 171 patients in each arm for 80% power and α-error 5%. Primary outcome was incidence of PEP, within 1 week, as defined by Cotton's criteria. All analysis were done by intention-to-treat. RESULTS Between October, 2017 to February, 2018, 521 patients were assessed. In all, 352 were enrolled, 178 randomized to vHR, and 174 to per-rectal Indomethacin. Baseline details and ERCP outcomes were not different between 2 groups. PEP occurred in 6 (1.7%) overall, with 1 (0.6%) in hydration arm, and 5 (2.9%) in indomethacin arm; an absolute risk reduction of 2.3% (95% confidence interval: 0.9%-3.5%) and odds ratio of 0.19 (95% confidence interval: 0.02-1.65). Three patients developed severe PEP, all receiving indomethacin. CONCLUSIONS vHR with LR is noninferior to postprocedure per-rectal Indomethacin for PEP prevention (ClinicalTrials.govID:NCT03629600).
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Tse F, Liu J, Yuan Y, Moayyedi P, Leontiadis GI. Guidewire-assisted cannulation of the common bile duct for the prevention of post-endoscopic retrograde cholangiopancreatography (ERCP) pancreatitis. Cochrane Database Syst Rev 2022; 3:CD009662. [PMID: 35349163 PMCID: PMC8963249 DOI: 10.1002/14651858.cd009662.pub3] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/18/2022]
Abstract
BACKGROUND Cannulation techniques have been recognized as being important in causing post-endoscopic retrograde cholangiopancreatography (ERCP) pancreatitis (PEP). However, considerable controversy exists about the usefulness of the guidewire-assisted cannulation technique for the prevention of PEP. OBJECTIVES To assess the effectiveness and safety of the guidewire-assisted cannulation technique compared to the conventional contrast-assisted cannulation technique for the prevention of PEP in people undergoing diagnostic or therapeutic ERCP for biliary or pancreatic diseases. SEARCH METHODS For the previous version of this review, we searched CENTRAL (the Cochrane Library), MEDLINE, Embase, CINAHL and major conference proceedings, up to February 2012, with no language restrictions. An updated search was performed on 26 February 2021 for the current version of this review. Two clinical trial registries, clinicaltrials.gov and WHO ICTRP, were also searched in this update. SELECTION CRITERIA Randomized controlled trials (RCTs) comparing the guidewire-assisted cannulation technique versus the contrast-assisted cannulation technique in people undergoing ERCP. DATA COLLECTION AND ANALYSIS Two review authors conducted study selection, data extraction, and methodological quality assessment independently. Using intention-to-treat analysis with random-effects models, we combined dichotomous data to obtain risk ratios (RR) with 95% confidence intervals (CI). We assessed heterogeneity using the Chi² test (P < 0.10) and I² statistic (> 50%). To explore sources of heterogeneity, we conducted a priori subgroup analyses according to trial design, publication type, risk of bias, use of precut sphincterotomy, inadvertent guidewire insertion or contrast injection of the pancreatic duct (PD), use of a PD stent, cannulation device, and trainee involvement in cannulation. To assess the robustness of our results, we carried out sensitivity analyses using different summary statistics (RR versus odds ratio (OR)) and meta-analytic models (fixed-effect versus random-effects) and per-protocol analysis. MAIN RESULTS 15 RCTs comprising 4426 participants were included. There was moderate heterogeneity among trials for the outcome of PEP (P = 0.08, I² = 36%). Meta-analyses suggest that the guidewire-assisted cannulation technique probably reduces the risk of PEP compared to the contrast-assisted cannulation technique (RR 0.51, 95% CI 0.36 to 0.72, 15 studies, moderate-certainty evidence). In addition, the guidewire-assisted cannulation technique may result in an increase in primary cannulation success (RR 1.06, 95% CI 1.01 to 1.12, 13 studies, low-certainty evidence), and probably reduces the need for precut sphincterotomy (RR 0.79, 95% CI 0.64 to 0.96, 10 studies, moderate-certainty evidence). Compared to the contrast-assisted cannulation technique, the guidewire-assisted cannulation technique may result in little to no difference in the risk of post-sphincterotomy bleeding (RR 0.87, 95% CI 0.49 to 1.54, 7 studies, low-certainty evidence) and perforation (RR 0.93, 95% CI 0.11 to 8.23, 8 studies, very low-certainty evidence). Procedure-related mortality was reported by eight studies, and there were no cases of deaths in both arms (moderate-certainty evidence). Subgroup analyses suggest that the heterogeneity for the outcome of PEP could be explained by differences in trial design. The results were robust in sensitivity analyses. AUTHORS' CONCLUSIONS There is moderate-certainty evidence that the guidewire-assisted cannulation technique probably reduces the risk of PEP compared to the contrast-assisted cannulation technique. There is low-certainty evidence that the guidewire-assisted cannulation technique may result in an increase in primary cannulation success. There is low- and very low-certainty evidence that the guidewire-assisted cannulation technique may result in little to no difference in the risk of bleeding and perforation. No procedure-related deaths were reported. Therefore, the guidewire-assisted cannulation technique appears to be superior to the contrast-assisted cannulation technique considering the certainty of evidence and the balance of benefits and harms. However, the routine use of guidewires in biliary cannulation will be dependent on local expertise, availability, and cost. Future research should assess the effectiveness and safety of the guidewire-assisted cannulation technique in the context of other pharmacologic or non-pharmacologic interventions for the prevention of PEP.
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Affiliation(s)
- Frances Tse
- Department of Medicine, Division of Gastroenterology, McMaster University, Hamilton, Canada
- Farncombe Family Digestive Health Research Institute, Hamilton, Canada
| | - Jasmine Liu
- Department of Medicine, McMaster University, Hamilton, Canada
| | - Yuhong Yuan
- Department of Medicine, Division of Gastroenterology, McMaster University, Hamilton, Canada
| | - Paul Moayyedi
- Department of Medicine, Division of Gastroenterology, McMaster University, Hamilton, Canada
- Farncombe Family Digestive Health Research Institute, Hamilton, Canada
| | - Grigorios I Leontiadis
- Department of Medicine, Division of Gastroenterology, McMaster University, Hamilton, Canada
- Farncombe Family Digestive Health Research Institute, Hamilton, Canada
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Sperna Weiland CJ, Smeets XJ, Verdonk RC, Poen AC, Bhalla A, Venneman NG, Kievit W, Timmerhuis HC, Umans DS, van Hooft JE, Besselink MG, van Santvoort HC, Fockens P, Bruno MJ, Drenth JP, van Geenen EJ, on behalf of the Dutch Pancreatitis Study Group . Optimal timing of rectal diclofenac in preventing post-endoscopic retrograde cholangiopancreatography pancreatitis. Endosc Int Open 2022; 10:E246-E253. [PMID: 35295242 PMCID: PMC8920594 DOI: 10.1055/a-1675-2108] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/30/2021] [Accepted: 09/21/2021] [Indexed: 12/11/2022] Open
Abstract
Background and study aims Rectal nonsteroidal anti-inflammatory drug (NSAID) prophylaxis reduces incidence of post-endoscopic retrograde cholangiopancreatography (ERCP) pancreatitis. Direct comparisons to the optimal timing of administration, before or after ERCP, are lacking. Therefore, we aimed to assess whether timing of rectal NSAID prophylaxis affects the incidence of post-ERCP pancreatitis. Patients and methods We conducted an analysis of prospectively collected data from a randomized clinical trial. We included patients with a moderate to high risk of developing post-ERCP pancreatitis, all of whom received rectal diclofenac monotherapy 100-mg prophylaxis. Administration was within 30 minutes before or after the ERCP at the discretion of the endoscopist. The primary endpoint was post-ERCP pancreatitis. Secondary endpoints included severity of pancreatitis, length of hospitalization, and Intensive Care Unit (ICU) admittance. Results We included 346 patients who received the rectal NSAID before ERCP and 63 patients who received it after ERCP. No differences in baseline characteristics were observed. Post-ERCP pancreatitis incidence was lower in the group that received pre-procedure rectal NSAIDs (8 %), compared to post-procedure (18 %) (relative risk: 2.32; 95% confidence interval: 1.21 to 4.46, P = 0.02). Hospital stays were significantly longer with post-procedure prophylaxis (1 day; interquartile range [IQR] 1-2 days vs. 1 day; IQR 1-4 days; P = 0.02). Patients from the post-procedure group were more likely to be admitted to the ICU (1 patient [0.3 %] vs. 4 patients [6 %]; P = 0.002). Conclusions Pre-procedure administration of rectal diclofenac is associated with a significant reduction in post-ERCP pancreatitis incidence compared to post-procedure use.
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Affiliation(s)
- Christina J. Sperna Weiland
- Department of Gastroenterology and Hepatology, Radboud Institute for Molecular Life Science, Radboudumc, Nijmegen, the Netherlands,Department of Research and Development, St. Antonius Hospital, Nieuwegein, the Netherlands
| | - Xavier J.N.M. Smeets
- Department of Gastroenterology and Hepatology, Jeroen Bosch ziekenhuis, Den Bosch, the Netherlands
| | - Robert C. Verdonk
- Department of Gastroenterology and Hepatology, St. Antonius Hospital, Nieuwegein, the Netherlands
| | - Alexander C. Poen
- Department of Gastroenterology and Hepatology, Isala Clinics, Zwolle, the Netherlands
| | - Abha Bhalla
- Department of Gastroenterology and Hepatology, Hagaziekenhuis, The Hague, the Netherlands
| | - Niels G. Venneman
- Department of Gastroenterology and Hepatology, Medisch Spectrum Twente, Enschede, the Netherlands
| | - Wietske Kievit
- Department for Health evidence, Radboudumc, Nijmegen, the Netherlands
| | - Hester C. Timmerhuis
- Department of Research and Development, St. Antonius Hospital, Nieuwegein, the Netherlands
| | - Devica S. Umans
- Department of Research and Development, St. Antonius Hospital, Nieuwegein, the Netherlands,Department of Gastroenterology and Hepatology, Amsterdam Gastroenterology Endocrinology Metabolism, Amsterdam UMC, Amsterdam, the Netherlands
| | - Jeanin E. van Hooft
- Department of Gastroenterology and Hepatology, Leiden University medical Centre, Leiden, the Netherlands
| | - Marc G. Besselink
- Department of Surgery, Amsterdam Gastroenterology Endocrinology Metabolism, Amsterdam UMC, Amsterdam, the Netherlands
| | - Hjalmar C. van Santvoort
- Department of Surgery, St Antonius Hospital, Nieuwegein, the Netherlands ,Department of Surgery, University Medical Centre Utrecht, Utrecht, the Netherlands
| | - Paul Fockens
- Department of Gastroenterology and Hepatology, Amsterdam Gastroenterology Endocrinology Metabolism, Amsterdam UMC, Amsterdam, the Netherlands
| | - Marco J. Bruno
- Department of Gastroenterology and Hepatology, Erasmus Medical Centre, Rotterdam, the Netherlands
| | - Joost P.H. Drenth
- Department of Gastroenterology and Hepatology, Radboud Institute for Molecular Life Science, Radboudumc, Nijmegen, the Netherlands
| | - Erwin J.M. van Geenen
- Department of Gastroenterology and Hepatology, Radboud Institute for Molecular Life Science, Radboudumc, Nijmegen, the Netherlands
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10
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Single-operator peroral pancreatoscopy in the preoperative diagnostics of suspected main duct intraductal papillary mucinous neoplasms: efficacy and novel insights on complications. Surg Endosc 2022; 36:7431-7443. [PMID: 35277769 PMCID: PMC9485081 DOI: 10.1007/s00464-022-09156-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/04/2021] [Accepted: 02/18/2022] [Indexed: 11/20/2022]
Abstract
Background Distinguishing intraductal papillary mucinous neoplasms (IPMNs) from other pancreatic cystic lesions is essential since IPMNs carry the risk of becoming malignant. Differentiating the main pancreatic duct involving IPMNs (MD-IPMNs) through conventional imaging is deficient. Single-operator peroral pancreatoscopy (SOPP) represents a promising method offering additional information on suspected lesions in the pancreatic main duct (MD). We aimed to determine the role of SOPP in the preoperative diagnostics of suspected MD-IPMNs and identify factors contributing to SOPP-related complications. Materials and Methods In this primarily retrospective study, SOPPs were performed at three high-volume centers on suspected MD-IPMNs. Primary outcome was the clinical impact of SOPP to subsequent patient care. Additionally, we documented post-SOPP complications and analyzed several assumed patient- and procedure-related risk factors. Results One hundred and one (101) SOPPs were performed. Subsequent clinical management was affected due to the findings in 86 (85%) cases. Surgery was planned for 29 (29%) patients. A condition other than IPMN explaining MD dilatation was found in 28 (28%) cases. In 35 (35%) cases, follow-up with MRI was continued. Post-SOPP pancreatitis occurred in 20 (20%) patients and one of them was fatal. A decrease in odds of post-SOPP pancreatitis was seen as the MD diameter increases (OR 0.714 for 1.0 mm increase in MD diameter, CI 95% 0.514–0.993, p = 0.045). Furthermore, a correlation between lower MD diameter values and higher severity post-SOPP pancreatitis was seen (TJT = 599, SE = 116.6, z = − 2.31; p = 0.020). History of pancreatitis after endoscopic retrograde cholangiopancreatography was a confirmed risk factor for post-SOPP pancreatitis. Conclusions between complications and other risk factors could not be drawn. Conclusion SOPP aids clinical decision-making in suspected MD-IPMNs. Risk for post-SOPP pancreatitis is not negligible compared to non-invasive imaging methods. The risk for pancreatitis decreases as the diameter of the MD increases.
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Laquière A, Privat J, Jacques J, Legros R, Urena-Campos R, Belkhodja H, Subtil C, Kanafi L, Lecomte L, Boustière C, Katsogiannou M, Karsenti D. Early double-guidewire versus repeated single-guidewire technique to facilitate selective bile duct cannulation: a randomized controlled trial. Endoscopy 2022; 54:120-127. [PMID: 33860484 DOI: 10.1055/a-1395-7485] [Citation(s) in RCA: 12] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/16/2022]
Abstract
BACKGROUND During endoscopic retrograde cholangiopancreatography (ERCP), access to the common bile duct (CBD) can be problematic after unintentional insertion of the guidewire into the pancreatic duct. We conducted a prospective, randomized study in order to compare biliary cannulation success rates of early double-guidewire (EDG) and repeated single-guidewire (RSG) techniques in patients with inadvertent passage of the guidewire into the pancreatic duct. METHODS Patients with a native papilla were randomly assigned to either the EDG or RSG groups after unintentional insertion of the guidewire into the pancreatic duct. The primary outcome was successful selective CBD cannulation within 10 minutes. The secondary outcomes were successful final selective bile duct cannulation, time to bile duct cannulation, and frequency of post-ERCP pancreatitis (PEP). RESULTS 142 patients were randomized and selective bile duct cannulation was achieved in 57/68 patients (84 %) in the EDG group and in 37/74 patients (50 %) in the RSG group within 10 minutes (relative risk 1.34; 95 % confidence interval 1.08-6.18; P < 0.001). The overall final selective bile duct cannulation rate was 99.3 %. The time to access the CBD was shorter using the EDG technique (6.0 vs. 10.4 minutes; P = 0.002). Mild PEP was not observed more frequently in the EDG group than in the RSG group. CONCLUSION The EDG technique significantly increased the success rate of biliary duct cannulation within 10 minutes compared with an RSG approach.
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Affiliation(s)
- Arthur Laquière
- Department of Gastroenterology, Saint Joseph Hospital, Marseille, France
| | - Jocelyn Privat
- Department of Gastroenterology, Jacques Lacarin Hospital, Vichy, France
| | - Jeremie Jacques
- Department of Endoscopy and Gastroenterology, Dupuytren Hospital, Limoges, France
| | - Romain Legros
- Department of Endoscopy and Gastroenterology, Dupuytren Hospital, Limoges, France
| | | | - Hichem Belkhodja
- Digestive Endoscopy Unit, University Hospital Lyon Sud, Lyon, France
| | - Clément Subtil
- Digestive Endoscopy Unit, University Hospital, Bordeaux, France
| | - Leïla Kanafi
- Department of Gastroenterology, Groupe Polyclinique Marzet-Navarre, Pau, France
| | - Laurence Lecomte
- Department of Gastroenterology, Saint Joseph Hospital, Marseille, France
| | | | - Maria Katsogiannou
- Department of Clinical Research, Saint Joseph Hospital, Marseille, France
| | - David Karsenti
- Digestive Endoscopy Unit, Pôle Digestif Paris Bercy, Clinique Paris-Bercy, Charenton-le-Pont, France
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12
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Thiruvengadam NR, Saumoy M, Schneider Y, Attala S, Triggs J, Lee P, Kochman ML. A Cost-Effectiveness Analysis for Post-Endoscopic Retrograde Cholangiopancreatography Pancreatitis Prophylaxis in the United States. Clin Gastroenterol Hepatol 2022; 20:216-226.e42. [PMID: 34481952 DOI: 10.1016/j.cgh.2021.08.050] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/03/2021] [Revised: 08/24/2021] [Accepted: 08/26/2021] [Indexed: 02/07/2023]
Abstract
BACKGROUND & AIMS Post-endoscopic retrograde cholangiopancreatography pancreatitis (PEP) is the most common adverse event after endoscopic retrograde cholangiopancreatography, and is responsible for substantial morbidity and health care expenditures of at least $200 million. Therapies for PEP prevention include pancreatic stent placement (PSP), rectal indomethacin, sublingual nitrates, and aggressive lactated Ringer's hydration. Our objective was to determine which PEP prophylactic strategies are cost effective. METHODS We developed 2 separate decision trees to evaluate PEP prophylactic strategies. The first, in high-risk patients, compared rectal indomethacin, PSP, PSP with indomethacin, sublingual nitrates, aggressive hydration with lactated Ringer's, and no prophylaxis. The second, in average-risk patients, compared rectal indomethacin, sublingual nitrates, aggressive hydration, and no prophylaxis. We used incidence rates, transition probabilities, and costs from publications and public data sources. Outcome measures were reported as incremental cost-effectiveness ratios, with a willingness-to-pay (WTP) threshold of $100,000/quality-adjusted life years (QALYs). RESULTS Compared with no prophylaxis, all strategies were cost effective at a WTP of $100,000 in preventing PEP in high-risk patients. When directly compared with each other, rectal indomethacin was the cost-effective strategy in high-risk patients ($31,589/QALYs). In average-risk patients, indomethacin and sublingual nitrates were cost effective at a WTP of $100,000/QALYs compared with no prophylaxis. When directly compared with each other, rectal indomethacin was the cost-effective strategy ($53,016/QALYs). CONCLUSIONS Rectal indomethacin was the cost-effective strategy for preventing PEP in both average-risk and high-risk patients undergoing endoscopic retrograde cholangiopancreatography. All strategies were cost effective when compared with no prophylaxis in high-risk patients, whereas all strategies except for aggressive hydration with lactated Ringer's were cost effective in average-risk patients. Further studies are needed to improve the utilization of PEP prevention strategies.
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Affiliation(s)
- Nikhil R Thiruvengadam
- Division of Gastroenterology and Hepatology, Loma Linda University Health, Loma Linda, California; Gastroenterology Division, Perelman School of Medicine, Philadelphia, Pennsylvania; Center for Endoscopic Innovation, Research and Training, Department of Medicine, Hospital of the University of Pennsylvania, Philadelphia, Pennsylvania.
| | - Monica Saumoy
- Gastroenterology Division, Perelman School of Medicine, Philadelphia, Pennsylvania
| | | | - Sara Attala
- Gastroenterology Division, Perelman School of Medicine, Philadelphia, Pennsylvania
| | - Joseph Triggs
- Gastroenterology Division, Perelman School of Medicine, Philadelphia, Pennsylvania
| | - Peter Lee
- Gastroenterology Division, Perelman School of Medicine, Philadelphia, Pennsylvania
| | - Michael L Kochman
- Gastroenterology Division, Perelman School of Medicine, Philadelphia, Pennsylvania; Center for Endoscopic Innovation, Research and Training, Department of Medicine, Hospital of the University of Pennsylvania, Philadelphia, Pennsylvania
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Machicado JD, Mounzer R, Paragomi P, Pothoulakis I, Hart PA, Conwell DL, de-Madaria E, Greer P, Yadav D, Whitcomb DC, Lee PJ, Hinton A, Papachristou GI. Rectal Indomethacin Does Not Mitigate the Systemic Inflammatory Response Syndrome in Acute Pancreatitis: A Randomized Trial. Clin Transl Gastroenterol 2021; 12:e00415. [PMID: 34704970 PMCID: PMC8553238 DOI: 10.14309/ctg.0000000000000415] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/30/2021] [Accepted: 08/16/2021] [Indexed: 12/12/2022] Open
Abstract
INTRODUCTION Experimental data suggest that nonsteroidal antiinflammatory drugs may prevent disease severity and mortality in acute pancreatitis (AP). The aim of this study was to compare the efficacy of rectal indomethacin vs placebo in reducing the systemic inflammatory response syndrome (SIRS) score in a high-risk AP population for clinical progression. METHODS We conducted a single-center, quadruple-blinded, randomized, placebo-controlled trial. Eligible criteria were subjects with AP and SIRS within 72 hours of presentation and those without organ failure. Subjects were allocated in a 1:1 ratio to indomethacin or placebo using simple randomization. Both interventions were administered rectally every 8 hours for 6 doses and compared using both intention-to-treat and per-protocol analyses. RESULTS A total of 42 subjects (mean age 52 years, 55% men) were randomized to indomethacin (n = 18) or placebo (n = 24). There was no significant difference between the indomethacin and placebo groups in the change of SIRS score, proportion of subjects with SIRS, and distribution of SIRS scores at 24, 48, and 72 hours from randomization. There were no significant differences in the change of C-reactive protein levels at 48 hours or clinical outcomes between both treatment groups. Indomethacin was as safe as placebo, with 2 adverse events occurring in the placebo and none in the indomethacin arm. DISCUSSION Rectal indomethacin can be safely administered over 48 hours; however, it is not superior to placebo in reducing the SIRS or clinical progression in a high-risk population with AP (ClinicalTrials.gov: NCT02692391).
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Affiliation(s)
- Jorge D. Machicado
- Division of Gastroenterology and Hepatology, University of Michigan, Ann Arbor, Michigan, USA;
| | - Rawad Mounzer
- Interventional Endoscopy Associates, Scottsdale, Arizona, USA;
| | - Pedram Paragomi
- Division of Gastroenterology, Hepatology and Nutrition, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania, USA;
| | - Ioannis Pothoulakis
- Division of Gastroenterology, Hepatology and Nutrition, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania, USA;
| | - Phil A. Hart
- Division of Gastroenterology, Hepatology and Nutrition, The Ohio State University Wexner Medical Center, Columbus, Ohio, USA;
| | - Darwin L. Conwell
- Division of Gastroenterology, Hepatology and Nutrition, The Ohio State University Wexner Medical Center, Columbus, Ohio, USA;
| | - Enrique de-Madaria
- Gastroenterology Department, Alicante University General Hospital, ISABIAL, Alicante, Spain;
| | - Phil Greer
- Division of Gastroenterology, Hepatology and Nutrition, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania, USA;
| | - Dhiraj Yadav
- Division of Gastroenterology, Hepatology and Nutrition, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania, USA;
| | - David C. Whitcomb
- Division of Gastroenterology, Hepatology and Nutrition, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania, USA;
| | - Peter J. Lee
- Division of Gastroenterology, Hepatology and Nutrition, The Ohio State University Wexner Medical Center, Columbus, Ohio, USA;
| | - Alice Hinton
- Division of Biostatistics, College of Public Health, the Ohio State University, Columbus, Ohio, USA.
| | - Georgios I. Papachristou
- Division of Gastroenterology, Hepatology and Nutrition, The Ohio State University Wexner Medical Center, Columbus, Ohio, USA;
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Márta K, Gede N, Szakács Z, Solymár M, Hegyi PJ, Tél B, Erőss B, Vincze Á, Arvanitakis M, Boškoski I, Bruno MJ, Hegyi P. Combined use of indomethacin and hydration is the best conservative approach for post-ERCP pancreatitis prevention: A network meta-analysis. Pancreatology 2021; 21:1247-1255. [PMID: 34353727 DOI: 10.1016/j.pan.2021.07.005] [Citation(s) in RCA: 18] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/15/2021] [Revised: 07/19/2021] [Accepted: 07/20/2021] [Indexed: 12/11/2022]
Abstract
OBJECTIVES Post-ERCP pancreatitis (PEP) is a life-threatening complication. Given the lack of a causative treatment for pancreatitis, it is of vital importance to minimize this risk of PEP. Multi-target preventive therapy may be the best choice for PEP prevention as disease development is multifactorial. AIM We aimed to assess the efficacy of a combination of indomethacin and hydration - type and amount - for PEP prevention via a network meta-analysis. METHODS Through a systematic search in three databases, we searched all randomized controlled trials involving hydration and indomethacin and ranked the PEP preventive efficacy with a Bayesian network meta-analysis using the PRISMA for Network Meta-Analyses (PRISMA-NMA) guideline. The RoB2 tool was used for risk of bias assessment, surface under the cumulative ranking curve (SUCRA) for ranking and PROSPERO for the study protocol [reg. no. CRD42018112698]. We used risk ratios (RR) for dichotomous data with 95% credible intervals (95% CrI). RESULTS The quantitative analysis included 7559 patients from 24 randomized controlled trials. Based on the SUCRA values, a combination of lactated Ringer's and indomethacin is more effective than single therapy with a 94% certainty. The percent relative risk ratios estimate preventive efficacy 70-99% higher for combinations than single therapies. Aggressive hydration with indomethacin (SUCRA 100%) is also significantly more effective than all other interventions (percent relative effect 94.3-98.1%). CONCLUSIONS A one-hit-on-each-target therapeutic approach is recommended in PEP prevention with an easily accessible combination of indomethacin and aggressive hydration for all average and high-risk patients without contraindication.
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Affiliation(s)
- Katalin Márta
- Institute for Translational Medicine, Szentágothai Research Centre, Medical School, University of Pécs, Pécs, Hungary; Division of Pancreatic Diseases, Heart and Vascular Center, Semmelweis University, Budapest, Hungary
| | - Noémi Gede
- Division of Pancreatic Diseases, Heart and Vascular Center, Semmelweis University, Budapest, Hungary; Institute of Bioanalysis, Medical School, University of Pécs, Pécs, Hungary
| | - Zsolt Szakács
- Institute for Translational Medicine, Szentágothai Research Centre, Medical School, University of Pécs, Pécs, Hungary; First Department of Medicine, Medical School, University of Pécs, Pécs, Hungary
| | - Margit Solymár
- Institute for Translational Medicine, Szentágothai Research Centre, Medical School, University of Pécs, Pécs, Hungary; First Department of Medicine, Medical School, University of Pécs, Pécs, Hungary
| | - Péter Jenő Hegyi
- Institute for Translational Medicine, Szentágothai Research Centre, Medical School, University of Pécs, Pécs, Hungary; Division of Pancreatic Diseases, Heart and Vascular Center, Semmelweis University, Budapest, Hungary; First Department of Medicine, Medical School, University of Pécs, Pécs, Hungary
| | - Bálint Tél
- First Department of Pediatrics, Semmelweis University, Budapest, Hungary
| | - Bálint Erőss
- Institute for Translational Medicine, Szentágothai Research Centre, Medical School, University of Pécs, Pécs, Hungary; Division of Pancreatic Diseases, Heart and Vascular Center, Semmelweis University, Budapest, Hungary; First Department of Medicine, Medical School, University of Pécs, Pécs, Hungary
| | - Áron Vincze
- Institute for Translational Medicine, Szentágothai Research Centre, Medical School, University of Pécs, Pécs, Hungary; First Department of Medicine, Medical School, University of Pécs, Pécs, Hungary
| | - Marianna Arvanitakis
- Gastroenterology Department, Gastrointestinal Cancer Unit, Erasme Hospital University, Brussels, Belgium
| | - Ivo Boškoski
- Centre for Endoscopic Research Therapeutics and Training (CERTT), Università Cattolica del Sacro Cuore, Italy
| | - Marco J Bruno
- Department of Gastroenterology & Hepatology, Erasmus Medical Center, University Medical Center Rotterdam, the Netherlands
| | - Péter Hegyi
- Institute for Translational Medicine, Szentágothai Research Centre, Medical School, University of Pécs, Pécs, Hungary; Division of Pancreatic Diseases, Heart and Vascular Center, Semmelweis University, Budapest, Hungary; Centre for Translational Medicine, Semmelweis University, Budapest, Hungary.
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15
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Yu S, Shen X, Li L, Bi X, Chen P, Wu W. Rectal indomethacin and diclofenac are equally efficient in preventing pancreatitis following endoscopic retrograde cholangiopancreatography in average-risk patients. JGH Open 2021; 5:1119-1126. [PMID: 34621996 PMCID: PMC8485396 DOI: 10.1002/jgh3.12643] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/23/2021] [Accepted: 08/04/2021] [Indexed: 11/22/2022]
Abstract
Rectal indomethacin and diclofenac are promising drugs for prevention of post‐endoscopic retrograde cholangiopancreatography (ERCP) pancreatitis (PEP). However, their prophylactic effect on PEP in average‐risk patients remains controversial. We performed a systematic review and meta‐analysis to assess the efficacy and safety of rectal indomethacin and diclofenac in average‐risk patients, and to indirectly compare the prophylactic effect of the two drugs. A comprehensive search of the PubMed, EMBASE, and Cochrane Library databases was performed to identify randomized controlled trials (RCTs) on rectal indomethacin or diclofenac for prophylaxis against PEP. Fixed‐ and random‐effects models weighted by the Mantel–Haenszel method were used for direct comparisons. The adjusted indirect treatment comparison method was used to indirectly compare the efficacy of indomethacin and diclofenac. A total of 10 RCTs, including 2928 patients, met our inclusion criteria. No significant publication bias was identified. Pooled estimates showed that rectal indomethacin and diclofenac were associated with a significant reduction in the overall risk of PEP compared with control intervention [relative risk (RR) = 0.62; 95% confidence interval (CI): 0.46–0.83] in average‐risk patients. Subgroup analyses showed that both rectal indomethacin (RR = 0.67; 95% CI: 0.49–0.94) and diclofenac (RR = 0.42; 95% CI: 0.23–0.75) were effective in the prevention of PEP. Indirect comparison showed no significant difference between the effectiveness of the two drugs in the prevention of PEP (RR = 1.607; 95% CI: 0.824–3.136). The updated meta‐analysis suggests that both drugs provide equivalent protection against PEP in average‐risk patients.
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Affiliation(s)
- Shuang Yu
- Department of Gastroenterology Chongqing University Three Gorges Hospital Chongqing China
| | - Xumu Shen
- Department of Gastroenterology Chongqing University Three Gorges Hospital Chongqing China
| | - Liang Li
- Department of Gastroenterology Chongqing University Three Gorges Hospital Chongqing China
| | - Xiaofei Bi
- Department of Gastroenterology Chongqing University Three Gorges Hospital Chongqing China
| | - Ping Chen
- Department of Gastroenterology Chongqing University Three Gorges Hospital Chongqing China
| | - Wei Wu
- Department of Gastroenterology Chongqing University Three Gorges Hospital Chongqing China
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16
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Thanage R, Jain S, Chandnani S, Udgirkar S, Nair S, Debnath P, Jain S, Rathi P. Is the Combination of Rectal Diclofenac and Intravenous Ringer Lactate Superior to Individual Therapy for Prophylaxis of Post-Endoscopic Retrograde Cholangiopancreatography Pancreatitis: A Prospective, Open-Label, Single-Center Randomized Trial. Pancreas 2021; 50:1236-1242. [PMID: 34714289 DOI: 10.1097/mpa.0000000000001903] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/10/2022]
Abstract
METHODS This was single-center, open-label, randomized trial. Patients who were undergoing ERCP and who were at high risk for the development of PEP were selected for the study. Patients were randomized into 3 treatment groups: diclofenac suppository group, RL group, and a combination group. RESULTS Eight of 57 patients (14.03%) in the diclofenac group, 9 of 57 patients (15.78%) in the RL group, and 6 of 57 patients (10.52%) in the combination group developed PEP. The incidence of PEP between the three groups was not statistically significant (P = 0.70). Serum amylase level of >252 U/L had 91.3% sensitivity and 92.6% specificity for the diagnosis of PEP. CONCLUSIONS Post-ERCP pancreatitis is usually mild to moderate 95% times. Female sex, age younger than 50 years, a benign indication of ERCP, and low bilirubin levels have higher chances of PEP. A combination of rectal diclofenac and hydration with RL does not offer better protection for PEP, as compared with individual prophylaxis.
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Affiliation(s)
- Ravi Thanage
- From the Department of Gastroenterology, Topiwala National Medical College and B.Y.L. Nair Hospital, Mumbai, India
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Tomishima K, Ishii S, Fujisawa T, Yatagai N, Kabemura D, Sato S, Amano N, Murata A, Tsuzura H, Sato S, Matsumoto K, Shimada Y, Genda T, Nagahara A, Isayama H. Does restricting fluid volume impact post-ERCP pancreatitis in patient with heart disease? Saudi J Gastroenterol 2021; 27:355-360. [PMID: 34213425 PMCID: PMC8656333 DOI: 10.4103/sjg.sjg_693_20] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/09/2022] Open
Abstract
METHODS Two hundred and forty seven of 480 patients with naïve papilla undergoing therapeutic ERCP between April 2013 and March 2018 were enrolled for the study. The following patient characteristics were investigated: age, sex, body mass index, previous diseases (heart disease, renal failure, cerebrovascular disorders, coexisting malignancy and pulmonary disease), history of PEP, common bile duct diameter, diverticula and volume of fluid infused 24 hours after the procedure. All ERCP cases had naïve papilla and had undergone treatment. RESULTS The incidence of PEP was 8.5%. Significant differences were observed in the volume of fluid infused between patients without and with a history of heart disease (1,380 vs. 1,755 mL). The mean volume of the infused fluid was significantly lower in the PEP than non-PEP group (1,483 vs. 1,688 mL, P = 0.02). Moreover, PEP incidence differed according to a fluid infusion cutoff of 1,000 mL (7 vs. 11 cases of PEP in those with ≦1,000 mL and >1,000 mL fluid volume, respectively, P < 0.001). CONCLUSION Restricted fluid volume was a newly identified risk factor for PEP, particularly in patients with heart and renal diseases as comorbidities.
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Affiliation(s)
- Ko Tomishima
- Department of Gastroenterology, Graduate School of Medicine, Juntendo University, Tokyo, Japan,Department of Gastroenterology and Hepatology, Juntendo University Shizuoka Hospital, Tokyo, Japan
| | - Shigeto Ishii
- Department of Gastroenterology, Graduate School of Medicine, Juntendo University, Tokyo, Japan
| | - Toshio Fujisawa
- Department of Gastroenterology, Graduate School of Medicine, Juntendo University, Tokyo, Japan
| | - Noboru Yatagai
- Department of Gastroenterology, Graduate School of Medicine, Juntendo University, Tokyo, Japan,Department of Gastroenterology and Hepatology, Juntendo University Shizuoka Hospital, Tokyo, Japan
| | - Daishi Kabemura
- Department of Gastroenterology, Graduate School of Medicine, Juntendo University, Tokyo, Japan,Department of Gastroenterology and Hepatology, Juntendo University Shizuoka Hospital, Tokyo, Japan
| | - Sho Sato
- Department of Gastroenterology and Hepatology, Juntendo University Shizuoka Hospital, Tokyo, Japan
| | - Nozomi Amano
- Department of Gastroenterology and Hepatology, Juntendo University Shizuoka Hospital, Tokyo, Japan
| | - Ayato Murata
- Department of Gastroenterology and Hepatology, Juntendo University Shizuoka Hospital, Tokyo, Japan
| | - Hironori Tsuzura
- Department of Gastroenterology and Hepatology, Juntendo University Shizuoka Hospital, Tokyo, Japan
| | - Shunsuke Sato
- Department of Gastroenterology and Hepatology, Juntendo University Shizuoka Hospital, Tokyo, Japan
| | - Kouhei Matsumoto
- Department of Gastroenterology, Graduate School of Medicine, Juntendo University, Tokyo, Japan,Department of Gastroenterology and Hepatology, Juntendo University Shizuoka Hospital, Tokyo, Japan
| | - Yuji Shimada
- Department of Gastroenterology and Hepatology, Juntendo University Shizuoka Hospital, Tokyo, Japan
| | - Takuya Genda
- Department of Gastroenterology and Hepatology, Juntendo University Shizuoka Hospital, Tokyo, Japan
| | - Akihito Nagahara
- Department of Gastroenterology, Graduate School of Medicine, Juntendo University, Tokyo, Japan,Department of Gastroenterology and Hepatology, Juntendo University Shizuoka Hospital, Tokyo, Japan
| | - Hiroyuki Isayama
- Department of Gastroenterology, Graduate School of Medicine, Juntendo University, Tokyo, Japan,Address for correspondence: Prof. Hiroyuki Isayama, Department of Gastroenterology, Graduate School of Medicine, Juntendo University, 2-1-1 Hongo, Bunkyo-ku, Tokyo - 113-8421, Japan. E-mail:
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18
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Weissman S, Ahmed M, Baniqued MR, Ehrlich D, Tabibian JH. Best practices for prevention of post-endoscopic retrograde cholangiopancreatography pancreatitis. World J Gastrointest Endosc 2021; 13:161-169. [PMID: 34163563 PMCID: PMC8209540 DOI: 10.4253/wjge.v13.i6.161] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/27/2021] [Revised: 04/14/2021] [Accepted: 05/21/2021] [Indexed: 02/06/2023] Open
Abstract
Acute pancreatitis is of one the most common gastroenterology-related indications for hospital admissions worldwide. With the widespread reliance on endoscopic retrograde cholangiopancreatography (ERCP) for the management of pancreaticobiliary conditions, post-ERCP pancreatitis (PEP) has come to represent an important etiology of acute pancreatitis. Despite many studies aiming to better understand the pathogenesis and prevention of this iatrogenic disorder, findings have been heterogeneous, and considerable variation in clinical practice exists. Herein, we review the literature regarding PEP with the goal to raise awareness of this entity, discuss recent data, and present evidence-based best practices. We believe this manuscript will be useful for gastrointestinal endoscopists as well as other specialists involved in the management of patients with PEP.
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Affiliation(s)
- Simcha Weissman
- Department of Medicine, Hackensack Meridian Health Palisades Medical Center, North Bergen, NJ 07047, United States
| | - Mohamed Ahmed
- Department of Medicine, Hackensack Meridian Health Palisades Medical Center, North Bergen, NJ 07047, United States
| | - Matthew R Baniqued
- Department of Medicine, Hackensack Meridian Health Palisades Medical Center, North Bergen, NJ 07047, United States
| | - Dean Ehrlich
- UCLA Vatche and Tamar Manoukian Division of Digestive Diseases, Los Angeles, CA 91342, United States
| | - James H Tabibian
- Director of Endoscopy, Division of Gastroenterology, Department of Medicine, Olive View-UCLA Medical Center, Sylmar, CA 91342, United States
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Romano-Munive AF, García-Correa JJ, García-Contreras LF, Ramírez-García J, Uscanga L, Barbero-Becerra VJ, Moctezuma-Velázquez C, Ochoa-Rubí JA, Toledo-Cuque J, Vázquez-Anaya G, Keil-Ríos D, Grajales-Figueroa G, Ramírez-Luna MÁ, Valdovinos-Andraca F, Zamora-Nava LE, Tellez-Avila F. Can topical epinephrine application to the papilla prevent pancreatitis after endoscopic retrograde cholangiopancreatography? Results from a double blind, multicentre, placebo controlled, randomised clinical trial. BMJ Open Gastroenterol 2021; 8:bmjgast-2020-000562. [PMID: 33558263 PMCID: PMC7871689 DOI: 10.1136/bmjgast-2020-000562] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/02/2020] [Revised: 01/11/2021] [Accepted: 01/13/2021] [Indexed: 12/23/2022] Open
Abstract
Background and study aims Post-endoscopic retrograde cholangiopancreatography (ERCP) pancreatitis (PEP) is a complication associated with important morbidity, occasional mortality and high costs. Preventive strategies are suboptimal as PEP continues to affect 4% to 9% of patients. Spraying epinephrine on the papilla may decrease oedema and prevent PEP. This study aimed to compare rectal indomethacin plus epinephrine (EI) versus rectal indomethacin plus sterile water (WI) for the prevention of PEP. Patients and methods This multicentre randomised controlled trial included patients aged >18 years with an indication for ERCP and naive major papilla. All patients received 100 mg of rectal indomethacin and 10 mL of sterile water or a 1:10 000 epinephrine dilution. Patients were asked about PEP symptoms via telephone 24 hours and 7 days after the procedure. The trial was stopped half way through after a new publication reported an increased incidence of PEP among patients receiving epinephrine. Results Of the 3602 patients deemed eligible, 3054 were excluded after screening. The remaining 548 patients were randomised to EI group (n=275) or WI group (n=273). The EI and WI groups had similar baseline characteristics. Patients in the EI group had a similar incidence of PEP to those in the WI group (3.6% (10/275) vs 5.12% (14/273), p=0.41). Pancreatic duct guidewire insertion was identified as a risk factor for PEP (OR 4.38, 95% CI (1.44 to 13.29), p=0.009). Conclusion Spraying epinephrine on the papilla was no more effective than rectal indomethacin alone for the prevention of PEP. Trial registration number This study was registered with ClinicalTrials.gov (NCT02959112).
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Affiliation(s)
| | | | | | | | - Luis Uscanga
- Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran, Tlalpan, Mexico
| | | | | | - Jorge A Ochoa-Rubí
- Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran, Tlalpan, Mexico
| | - Julio Toledo-Cuque
- Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran, Tlalpan, Mexico
| | - Gerardo Vázquez-Anaya
- Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran, Tlalpan, Mexico
| | - Daniel Keil-Ríos
- Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran, Tlalpan, Mexico
| | | | | | | | | | - Felix Tellez-Avila
- Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran, Tlalpan, Mexico
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20
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Boškoski I, Costamagna G. How to Prevent Post-Endoscopic Retrograde Cholangiopancreatography Pancreatitis. Gastroenterology 2020; 158:2037-2040. [PMID: 32197979 DOI: 10.1053/j.gastro.2020.03.019] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Affiliation(s)
- Ivo Boškoski
- Digestive Endoscopy Unit, Fondazione Policlinico Universitario Agostino Gemelli IRCCS; and Centre for Endoscopic Research, Therapeutics and Training (CERTT), Catholic University of Rome, Rome, Italy.
| | - Guido Costamagna
- Digestive Endoscopy Unit, Fondazione Policlinico Universitario Agostino Gemelli IRCCS; and Centre for Endoscopic Research, Therapeutics and Training (CERTT), Catholic University of Rome, Rome, Italy
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21
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Koskensalo V, Tenca A, Udd M, Lindström O, Rainio M, Jokelainen K, Kylänpää L, Färkkilä M. Diclofenac does not reduce the risk of acute pancreatitis in patients with primary sclerosing cholangitis after endoscopic retrograde cholangiography. United European Gastroenterol J 2020; 8:462-471. [PMID: 32213036 DOI: 10.1177/2050640620912608] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/14/2022] Open
Abstract
BACKGROUND The European Society of Gastrointestinal Endoscopy recommends rectal indomethacin or diclofenac before endoscopic retrograde cholangiopancreatography (ERCP) to prevent post-ERCP pancreatitis. However, data on the prophylactic effect in patients with primary sclerosing cholangitis (PSC) are lacking. METHODS This was a retrospective case-control study. In 2009-2018, a total of 2000 ERCPs were performed in 931 patients with PSC. Case procedures (N = 1000 after November 2013) were performed after administration of rectal diclofenac. Control procedures (N = 1000 before November 2013) were performed with the same indication but without diclofenac. Acute post-ERCP pancreatitis and other ERCP-related adverse events (AEs) were evaluated. RESULTS Post-ERCP pancreatitis developed in 49 (4.9%) procedures in the diclofenac group and 62 (6.2%) procedures in the control group (p = 0.241). No difference existed between the groups in terms of the severity of pancreatitis or any other acute AEs. The risk of pancreatitis was elevated in patients with native papilla: 11.4% in the diclofenac group and 8.7% in the control group (p = 0.294). In adjusted logistic regression, diclofenac did not reduce the risk of pancreatitis (odds ratio (OR) = 1.074, 95% confidence interval 0.708-1.629, p = 0.737). However, in generalised estimation equations with the advanced model, diclofenac seemed to diminish the risk of pancreatitis (OR = 0.503) but not significantly (p = 0.110). CONCLUSION In this large patient cohort in a low-risk unit, diclofenac does not seem to reduce the risk of post-ERCP pancreatitis in patients with PSC. The trend in the pancreatitis rate after ERCP is decreasing. The evaluation of the benefits of diclofenac among PSC patients warrants a randomised controlled study targeted to high-risk patients and procedures.
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Affiliation(s)
- Vilja Koskensalo
- Faculty of Medicine, University of Helsinki, Helsinki, Finland.,Abdominal Centre, Gastroenterological Surgery, Helsinki University Hospital, Helsinki, Finland
| | - Andrea Tenca
- Faculty of Medicine, University of Helsinki, Helsinki, Finland.,Abdominal Centre, Gastroenterology, Helsinki University Hospital, Helsinki, Finland
| | - Marianne Udd
- Faculty of Medicine, University of Helsinki, Helsinki, Finland.,Abdominal Centre, Gastroenterological Surgery, Helsinki University Hospital, Helsinki, Finland
| | - Outi Lindström
- Faculty of Medicine, University of Helsinki, Helsinki, Finland.,Abdominal Centre, Gastroenterological Surgery, Helsinki University Hospital, Helsinki, Finland
| | - Mia Rainio
- Faculty of Medicine, University of Helsinki, Helsinki, Finland.,Abdominal Centre, Gastroenterological Surgery, Helsinki University Hospital, Helsinki, Finland
| | - Kalle Jokelainen
- Faculty of Medicine, University of Helsinki, Helsinki, Finland.,Abdominal Centre, Gastroenterology, Helsinki University Hospital, Helsinki, Finland
| | - Leena Kylänpää
- Faculty of Medicine, University of Helsinki, Helsinki, Finland.,Abdominal Centre, Gastroenterological Surgery, Helsinki University Hospital, Helsinki, Finland
| | - Martti Färkkilä
- Faculty of Medicine, University of Helsinki, Helsinki, Finland.,Abdominal Centre, Gastroenterology, Helsinki University Hospital, Helsinki, Finland
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22
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Avila P, Holmes I, Kouanda A, Arain M, Dai SC. Practice patterns of post-ERCP pancreatitis prophylaxis techniques in the United States: a survey of advanced endoscopists. Gastrointest Endosc 2020; 91:568-573.e2. [PMID: 31743690 DOI: 10.1016/j.gie.2019.11.013] [Citation(s) in RCA: 31] [Impact Index Per Article: 6.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/09/2019] [Accepted: 11/03/2019] [Indexed: 12/11/2022]
Abstract
BACKGROUND AND AIMS The American Society for Gastrointestinal Endoscopy recommends prophylactic pancreatic duct stent placement (PPS) and rectal nonsteroidal anti-inflammatory drugs (NSAIDs) to reduce the incidence and severity of post-ERCP pancreatitis (PEP) in high-risk individuals and suggests that rectal indomethacin may decrease the risk and severity of PEP in average-risk individuals. The European Society for Gastrointestinal Endoscopy recommends rectal indomethacin for all patients undergoing ERCP. Previous surveys of European endoscopists revealed low adoption of PPS or rectal NSAIDs to prevent PEP. We sought to capture current practice in the prevention of PEP among endoscopists in the United States involved in advanced endoscopy fellowship programs. METHODS An anonymous online 16-item survey was e-mailed to 233 advanced endoscopists involved in advanced endoscopy fellowship programs. RESULTS Of the 233 endoscopists who were invited to participate, 62 responded (26.7%). Most respondents reported working in tertiary referral centers (57; 95.0%) and performing ERCP for greater than 5 years (44; 74.6%). All respondents (60; 100.0%) reported working with fellows. Most PPS users (41; 72.0%) reported use of PPS in high-risk patients only and using PPS for PEP in ≤25% of ERCPs (38; 64.4%). Most respondents reported using rectal NSAIDs for high-risk patients only (34; 59.7%) compared with respondents (23; 40.1%) who reported using rectal NSAIDs for prevention of PEP in average-risk patients undergoing ERCP. Most respondents (49; 83.0%) also reported using rapid intravenous fluids to prevent PEP. CONCLUSIONS Among endoscopists involved in advanced endoscopy fellowships in the United States, rectal NSAIDs are used more frequently than PPS in the prevention of PEP. Despite mounting evidence supporting the use of rectal NSAIDs to prevent PEP in average-risk patients, less than half of the respondents in this survey reported such practice.
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Affiliation(s)
- Patrick Avila
- Division of Gastroenterology, University of California, San Francisco, San Francisco, California, USA
| | - Ian Holmes
- Division of Gastroenterology, University of California, San Francisco, San Francisco, California, USA
| | - Abdul Kouanda
- Division of Gastroenterology, University of California, San Francisco, San Francisco, California, USA
| | - Mustafa Arain
- Division of Gastroenterology, University of California, San Francisco, San Francisco, California, USA
| | - Sun-Chuan Dai
- Division of Gastroenterology, University of California, San Francisco, San Francisco, California, USA; Division of Gastroenterology, Zuckerberg San Francisco General Hospital and Trauma Center, San Francisco, California, USA
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23
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Fogel EL, Lehman GA, Tarnasky P, Cote GA, Schmidt SE, Waljee AK, Higgins PDR, Watkins JL, Sherman S, Kwon RSY, Elta GH, Easler JJ, Pleskow DK, Scheiman JM, El Hajj II, Guda NM, Gromski MA, McHenry L, Arol S, Korsnes S, Suarez AL, Spitzer R, Miller M, Hofbauer M, Elmunzer BJ. Rectal indometacin dose escalation for prevention of pancreatitis after endoscopic retrograde cholangiopancreatography in high-risk patients: a double-blind, randomised controlled trial. Lancet Gastroenterol Hepatol 2020; 5:132-141. [PMID: 31780277 PMCID: PMC10576534 DOI: 10.1016/s2468-1253(19)30337-1] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/07/2019] [Revised: 10/03/2019] [Accepted: 10/03/2019] [Indexed: 02/08/2023]
Abstract
BACKGROUND Although rectal indometacin 100 mg is effective in reducing the frequency and severity of pancreatitis after endoscopic retrograde cholangiopancreatography (ERCP) in high-risk patients, the optimal dose is unknown, and pancreatitis incidence remains high. The aim of this study was to compare the efficacy of two dose regimens of rectal indometacin on the frequency and severity of pancreatitis after ERCP in high-risk patients. METHODS In this randomised, double-blind, comparative effectiveness trial, we enrolled patients from six tertiary medical centres in the USA. Eligible patients were those at high risk for the development of pancreatitis after ERCP. We randomly assigned eligible patients (1:1) immediately after ERCP to receive either two 50 mg indometacin suppositories and a placebo suppository (standard-dose group) or three 50 mg indometacin suppositories (high-dose group). 4 h after the procedure, patients assigned to the high-dose group received an additional 50 mg indometacin suppository, whereas patients in the standard-dose group received an additional placebo suppository. The randomisation schedule, stratified according to study centre and with no other restrictions, was computer generated by an investigator who was uninvolved in the clinical care of any participants, distributed to the sites, and kept by personnel not directly involved with the study. These same personnel were responsible for packaging the drug and placebo in opaque envelopes. Patients, study personnel, and treating physicians were masked to study group assignment. The primary outcome of the study was the development of pancreatitis after ERCP. Analyses were done on an intention-to-treat basis. This trial is registered with ClinicalTrials.gov, number NCT01912716, and enrolment is complete. FINDINGS Between July 9, 2013, and March 22, 2018, 1037 eligible patients were enrolled and randomly assigned to receive either standard-dose (n=515) or high-dose indometacin (n=522). Pancreatitis after ERCP occurred in 141 (14%) of 1037 patients-76 (15%) of 515 patients in the standard-dose indometacin group and 65 (12%) of 522 patients in the high-dose indometacin group (risk ratio [RR] 1·19, 95% CI 0·87-1·61; p=0·32). We observed 19 adverse events that were potentially attributable to study drug. Clinically significant bleeding occurred in 14 (1%) of 1037 patients-six (1%) of 515 patients in the standard-dose indometacin group and eight (2%) of 522 patients in the high-dose indometacin group (p=0·79). Three (1%) of 522 patients in the high-dose indometacin group developed acute kidney injury versus none in the standard-dose group (p=0·25). A non-ST elevation myocardial infarction occurred in the standard-dose indometacin group 2 days after ERCP. A transient ischaemic attack occurred in the high-dose indometacin group 5 days after ERCP. All 19 adverse events, in addition to the 141 patients who developed pancreatitis after ERCP, were considered serious as all required admission to hospital. We observed no allergic reactions or deaths at 30 day follow-up. INTERPRETATION Dose escalation to rectal indometacin 200 mg did not confer any advantage compared with the standard 100 mg regimen, with pancreatitis incidence remaining high in high-risk patients. Current practice should continue unchanged. Further research should consider the pharmacokinetics of non-steroidal anti-inflammatory drugs to determine the optimal timing of their administration to prevent pancreatitis after ERCP. FUNDING American College of Gastroenterology.
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Affiliation(s)
- Evan L Fogel
- Division of Gastoenterology and Hepatology, Indiana University, Indianapolis, IN, USA.
| | - Glen A Lehman
- Division of Gastoenterology and Hepatology, Indiana University, Indianapolis, IN, USA
| | - Paul Tarnasky
- University of Texas Southwestern, Digestive Health Associates of Texas, Dallas, TX, USA
| | - Gregory A Cote
- Division of Gastroenterology, Medical University of South Carolina, Charleston, SC, USA
| | - Suzette E Schmidt
- Division of Gastoenterology and Hepatology, Indiana University, Indianapolis, IN, USA
| | - Akbar K Waljee
- Division of Gastroenterology, University of Michigan, Ann Arbor, MI, USA
| | - Peter D R Higgins
- Division of Gastroenterology, University of Michigan, Ann Arbor, MI, USA
| | - James L Watkins
- Division of Gastoenterology and Hepatology, Indiana University, Indianapolis, IN, USA
| | - Stuart Sherman
- Division of Gastoenterology and Hepatology, Indiana University, Indianapolis, IN, USA
| | - Richard S Y Kwon
- Division of Gastroenterology, University of Michigan, Ann Arbor, MI, USA
| | - Grace H Elta
- Division of Gastroenterology, University of Michigan, Ann Arbor, MI, USA
| | - Jeffrey J Easler
- Division of Gastoenterology and Hepatology, Indiana University, Indianapolis, IN, USA
| | - Douglas K Pleskow
- Division of Gastroenterology, Beth Israel Deaconess Medical Center, Boston, MA, USA
| | - James M Scheiman
- Division of Gastroenterology, University of Virginia, Charlottesville, VA, USA
| | - Ihab I El Hajj
- Division of Gastoenterology and Hepatology, Indiana University, Indianapolis, IN, USA; Division of Gastroenterology, University of Balamand, Beirut, Lebanon
| | - Nalini M Guda
- Division of Gastroenterology, University of Wisconsin, Milwaukee, WI, USA; Aurora St Luke's Medical Center, Milwaukee, WI, USA
| | - Mark A Gromski
- Division of Gastoenterology and Hepatology, Indiana University, Indianapolis, IN, USA
| | - Lee McHenry
- Division of Gastoenterology and Hepatology, Indiana University, Indianapolis, IN, USA
| | - Seena Arol
- University of Texas Southwestern, Digestive Health Associates of Texas, Dallas, TX, USA
| | - Sheryl Korsnes
- Division of Gastroenterology, University of Michigan, Ann Arbor, MI, USA
| | - Alejandro L Suarez
- Division of Gastroenterology, Medical University of South Carolina, Charleston, SC, USA; Division of Gastroenterology, Yale University, New Haven, CT, USA
| | - Rebecca Spitzer
- Division of Gastroenterology, Medical University of South Carolina, Charleston, SC, USA
| | - Marilyn Miller
- Division of Gastroenterology, University of Wisconsin, Milwaukee, WI, USA
| | - Maria Hofbauer
- Division of Gastroenterology, Beth Israel Deaconess Medical Center, Boston, MA, USA
| | - B Joseph Elmunzer
- Division of Gastroenterology, Medical University of South Carolina, Charleston, SC, USA
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24
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Johnson KD, Perisetti A, Tharian B, Thandassery R, Jamidar P, Goyal H, Inamdar S. Endoscopic Retrograde Cholangiopancreatography-Related Complications and Their Management Strategies: A "Scoping" Literature Review. Dig Dis Sci 2020; 65:361-375. [PMID: 31792671 DOI: 10.1007/s10620-019-05970-3] [Citation(s) in RCA: 47] [Impact Index Per Article: 9.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/04/2019] [Accepted: 11/16/2019] [Indexed: 12/12/2022]
Abstract
Endoscopic retrograde cholangiopancreatography (ERCP) is a well-known procedure with both diagnostic and therapeutic utilities in managing pancreaticobiliary conditions. With the advancements of endoscopic techniques, ERCP has become a relatively safe and effective procedure. However, as ERCP is increasingly being utilized for different advanced techniques, newer complications have been noticed. Post-ERCP complications are known, and mostly include pancreatitis, infection, hemorrhage, and perforation. The risks of these complications vary depending on several factors, such as patient selection, endoscopist's skills, and the difficulties involved during the procedure. This review discusses post-ERCP complications and management strategies with new and evolving concepts.
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Affiliation(s)
- Kemmian D Johnson
- Department of Internal Medicine, Louisiana State University Health Sciences Center, 1542 Tulane Ave Suite 436, New Orleans, LA, 70112, USA
| | - Abhilash Perisetti
- Department of Gastroenterology and Hepatology, University of Arkansas for Medical Sciences, 4301 W Markham St, Little Rock, AR, 72205, USA
| | - Benjamin Tharian
- Department of Gastroenterology and Hepatology, University of Arkansas for Medical Sciences, 4301 W Markham St, Little Rock, AR, 72205, USA
| | - Ragesh Thandassery
- University of Arkansas for Medical Sciences, 4301 W Markham St, Little Rock, AR, 72205, USA
- VISN-16 MD Lead for Advanced Liver Disease, CAVHS, Little Rock, USA
| | - Priya Jamidar
- Yale University School of Medicine, 333 Cedar Street-1080 LMP, P.O. Box 208019, New Haven, CT, 06520, USA
| | - Hemant Goyal
- Department of Internal Medicine, The Wright Center for Graduate Medical Education, 111 North Washington Avenue, Scranton, PA, 18503, USA.
| | - Sumant Inamdar
- Department of Gastroenterology and Hepatology, University of Arkansas for Medical Sciences, 4301 W Markham St, Little Rock, AR, 72205, USA
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Nonsteroidal Anti-inflammatory Drugs for Endoscopic Retrograde Cholangiopancreatography Postoperative Pancreatitis Prevention: a Systematic Review and Meta-analysis. J Gastrointest Surg 2019; 23:1991-2001. [PMID: 30251071 DOI: 10.1007/s11605-018-3967-7] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/11/2018] [Accepted: 09/07/2018] [Indexed: 02/06/2023]
Abstract
BACKGROUND OR PURPOSE There is controversy regarding the efficacy of nonsteroidal anti-inflammatory drugs (NSAIDs) for prophylaxis against endoscopic retrograde cholangiopancreatography (ERCP) postoperative pancreatitis. Therefore, we conducted a systematic review and meta-analysis to evaluate the efficacy of NSAIDs for prophylaxis against post-ERCP pancreatitis (PEP). METHODS PubMed, EMBASE, and Cochrane library databases were searched for relevant randomized controlled trials (RCTs). Selected RCTs were pooled under a fixed effects model to generate the relative risks (RRs) and their corresponding 95% confidence intervals (CIs). RESULTS Nineteen RCTs involving a total of 5031 patients (2555 in the intervention group and 2476 in the control group) were selected. Overall, NSAIDs were associated with a significant reduction in risk of PEP (RR = 0.54, 95% CI 0.45 to 0.64, I2 = 40.4%) and moderate to severe PEP (RR = 0.45, 95% CI 0.30 to 0.67, I2 = 0%) compared with the control group. Subgroup analyses were performed according to route of administration (rectal or other), type of NSAIDs (diclofenac, indomethacin, or other), timing of administration (pre-ERCP, post-ERCP, or other), and patient population (high risk or general). Subgroup analyses showed difference in clinical efficacy of NSAID prophylaxis regardless of route, timing, or specific type of NSAID. CONCLUSION NSAIDs were associated with a significant reduction in risk of PEP and moderate to severe PEP compared to the control group.
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Abstract
PURPOSE OF REVIEW The present article will focus in pharmacologic agents that have been studied to improve acute pancreatitis outcomes, and to prevent the disease at different levels. RECENT FINDINGS Too little and too much early fluid resuscitation can be harmful. The optimal volume, rate, and duration of intravenous fluid therapy is still unknown. Nonopioid analgesics should be the first line of analgesia in patients with acute pancreatitis. A few pharmacologic agents evaluated in acute pancreatitis have resulted in positive pilot trials; however, larger randomized clinical trials (RCTs) are needed before final conclusions. Statin use is associated with lower incidence of acute pancreatitis in the general population and ongoing studies are evaluating its preventive role in acute pancreatitis recurrences. The preventive role of rectal indomethacin in post-endoscopic retrograde cholangiopancreatography pancreatitis is indisputable, with subject selection and timing of administration requiring further investigation. SUMMARY There is still no proven effective disease-specific pharmacologic therapy that changes the natural history of acute pancreatitis. New therapeutic targets and pharmacologic agents are in the horizon. Careful refinement in study design is needed when planning future RCTs. There is also a need for drug development aiming at reducing the incidence of the disease and preventing its sequelae.
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27
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Does rectal ketoprofen prevent post ERCP pancreatitis? Arab J Gastroenterol 2019; 20:141-144. [DOI: 10.1016/j.ajg.2019.09.004] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/16/2019] [Revised: 07/17/2019] [Accepted: 09/15/2019] [Indexed: 02/07/2023]
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van Wanrooij RLJ, van Hooft JE. Prevention of post-ERCP pancreatitis: NSAID or pancreatic stent or both? Endosc Int Open 2019; 7:E869-E870. [PMID: 31288260 PMCID: PMC6609235 DOI: 10.1055/a-0889-7796] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/08/2022] Open
Affiliation(s)
- R. L. J. van Wanrooij
- Department of Gastroenterology and Hepatology, Amsterdam University Medical Center, Amsterdam, The Netherlands
| | - J. E. van Hooft
- Department of Gastroenterology and Hepatology, Amsterdam University Medical Center, Amsterdam, The Netherlands
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Bai Y, Li DF, Wang SL, Zhao SB, Ma SR, Zhang ST, Li ZS. Chinese expert consensus on perioperative medications for endoscopic retrograde cholangiopancreatography (ERCP). J Dig Dis 2019; 20:103-113. [PMID: 30604509 DOI: 10.1111/1751-2980.12699] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/27/2018] [Revised: 12/22/2018] [Accepted: 01/02/2019] [Indexed: 02/06/2023]
Affiliation(s)
- Yu Bai
- Department of Gastroenterology, Changhai Hospital, The Naval Medical University (Second Military Medical University), Shanghai, China
| | - De Feng Li
- Department of Gastroenterology, Shenzhen People's Hospital (Second Clinical Medical College of Jinan University, Shenzhen, Guangdong Province, China
| | - Shu Ling Wang
- Department of Gastroenterology, Changhai Hospital, The Naval Medical University (Second Military Medical University), Shanghai, China
| | - Sheng Bing Zhao
- Department of Gastroenterology, Changhai Hospital, The Naval Medical University (Second Military Medical University), Shanghai, China
| | - Shu Ren Ma
- Department of Gastroenterology, The General Hospital of Northern Theater Command, Shenyang, Liaoning Province, China
| | - Shu Tian Zhang
- Department of Gastroenterology, Beijing Friendship Hospital, Capital Medical University, Beijing, China
| | - Zhao Shen Li
- Department of Gastroenterology, Changhai Hospital, The Naval Medical University (Second Military Medical University), Shanghai, China
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30
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Pavel L, Bălan GG, Nicorescu A, Gîlcă-Blanariu GE, Sfarti C, Chiriac Ș, Diaconescu S, Drug VL, Bălan G, Ștefănescu G. Split-dose or hybrid nonsteroidal anti-inflammatory drugs and N-acetylcysteine therapy for prevention of post-retrograde cholangiopancreatography pancreatitis. World J Clin Cases 2019; 7:300-310. [PMID: 30746371 PMCID: PMC6369386 DOI: 10.12998/wjcc.v7.i3.300] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/28/2018] [Revised: 12/18/2018] [Accepted: 12/24/2018] [Indexed: 02/05/2023] Open
Abstract
BACKGROUND Despite significant technical and training improvements, the incidence of post-endoscopic retrograde cholangiopancreatography (ERCP) pancreatitis (PEP) has not significantly dropped. Although many studies have evaluated the efficacy of various agents, e.g. nonsteroidal anti-inflammatory drugs, octreotide, antioxidants, administered via various dosages, routes (oral, intrarectal or parenteral), and schedules (before or after the procedure), the results have been conflicting.
AIM To evaluate efficacy of three pharmacologic prophylactic methods for prevention of PEP.
METHODS In this prospective, single-center randomized trial, patients who underwent first-time ERCP for choledocholithiasis were randomly assigned to three groups. The first group received 600 mg N-acetylcysteine 15 min prior to ERCP, and per-rectum administration of 50 mg indomethacin both prior to and after completion of the ERCP. The second group was administered only the 50 mg indomethacin per-rectum both prior to and after the ERCP. The third group was administered per-rectum 100 mg indomethacin only after the ERCP, representing the control group given the guideline-recommended regimen. The primary end-point was PEP prevention.
RESULTS Among the total 211 patients evaluated during the study, 186 fulfilled the inclusion criteria and completed the protocol. The percentages of patients who developed PEP in each of the three groups were not significantly different (χ2 = 2.793, P = 0.247). Among the acute PEP cases, for all groups, 14 patients developed mild pancreatitis (77.77%) and 4 moderate. No severe cases of PEP occurred, and in all PEP cases the resolution was favorable. No adverse events related to the medications (digestive hemorrhage, rectal irritation, or allergies) occurred.
CONCLUSION The efficacies of split-dose indomethacin and combined administration (N-acetylcysteine with indomethacin) for preventing PEP were similar to that of the standard regimen.
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Affiliation(s)
- Laura Pavel
- Gastroenterology, “Grigore T. Popa” University of Medicine and Pharmacy, Iași 700115, România
| | - Gheorghe Gh Bălan
- Gastroenterology, “Grigore T. Popa” University of Medicine and Pharmacy, Iași 700115, România
| | - Alexandra Nicorescu
- Endocrinology, “Grigore T. Popa” University of Medicine and Pharmacy, Iași 700115, România
| | | | - Cătălin Sfarti
- Gastroenterology, “Grigore T. Popa” University of Medicine and Pharmacy, Iași 700115, România
| | - Ștefan Chiriac
- Gastroenterology, “Grigore T. Popa” University of Medicine and Pharmacy, Iași 700115, România
| | - Smaranda Diaconescu
- Department of Mother and Child Medicine, “Grigore T. Popa” University of Medicine and Pharmacy, Iași 700115, România
| | - Vasile Liviu Drug
- Gastroenterology, “Grigore T. Popa” University of Medicine and Pharmacy, Iași 700115, România
| | - Gheorghe Bălan
- Gastroenterology, “Grigore T. Popa” University of Medicine and Pharmacy, Iași 700115, România
| | - Gabriela Ștefănescu
- Gastroenterology, “Grigore T. Popa” University of Medicine and Pharmacy, Iași 700115, România
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Kamal A, Akshintala VS, Talukdar R, Goenka MK, Kochhar R, Lakhtakia S, Ramchandani MK, Sinha S, Goud R, Rai VK, Tandan M, Gupta R, Elmunzer BJ, Ngamruengphong S, Kumbhari V, Khashab MA, Kalloo AN, Reddy DN, Singh VK. A Randomized Trial of Topical Epinephrine and Rectal Indomethacin for Preventing Post-Endoscopic Retrograde Cholangiopancreatography Pancreatitis in High-Risk Patients. Am J Gastroenterol 2019; 114:339-347. [PMID: 30730860 DOI: 10.14309/ajg.0000000000000049] [Citation(s) in RCA: 20] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
INTRODUCTION Rectal indomethacin and topical spray of epinephrine have separately shown efficacy in the prevention of post-endoscopic retrograde cholangiopancreatography pancreatitis (PEP) in randomized controlled trials. We hypothesized that the combination of indomethacin and topical spray of epinephrine on the duodenal papillae would further reduce PEP than when indomethacin was used alone. METHODS We conducted a comparative effectiveness, multicenter, double-blinded, randomized trial of rectal indomethacin alone vs a combination of rectal indomethacin and topical spray of epinephrine for the prevention of PEP in high-risk patients. The primary outcome was the incidence of PEP and the secondary outcome was the severity of PEP. A 2-tailed Fisher's exact test was used to analyze the difference in the proportion of patients with PEP in the indomethacin alone vs the combination group. RESULTS A total of 960 patients (mean age 52.33 ± 14.96 years; 551 [57.4%] females) were randomized and 959 completed follow-up. The baseline demographic and clinical characteristics were similar between the 2 groups. Women <50 years of age (25.4%) and difficult cannulation (84.9%) were the most common PEP risk factors. The incidence of PEP was 6.4% in the indomethacin alone group (n = 482) compared to 6.7% in the combination group (n = 477; P = 0.87). Severe PEP was found in 5 (12%) and 7 (16%) patients in the indomethacin alone and combination groups, respectively (P = 0.88). The overall mortality was 0.6%, which was unrelated to the primary outcome. CONCLUSIONS The combination of rectal indomethacin and topical spray of epinephrine does not reduce the incidence of PEP compared to rectal indomethacin alone in high-risk patients; https://clinicaltrials.gov/ct2/show/NCT02116309.
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Affiliation(s)
- Ayesha Kamal
- Division of Gastroenterology, Johns Hopkins Medical Institutions, Baltimore, Maryland, USA
| | - Venkata S Akshintala
- Division of Gastroenterology, Johns Hopkins Medical Institutions, Baltimore, Maryland, USA
| | | | - Mahesh K Goenka
- Institute of Gastroenterology, Apollo Gleneagles Hospital, Kolkata, India
| | - Rakesh Kochhar
- Division of Gastroenterology, Postgraduate Institute of Medical Education and Research, Chandigarh, India
| | | | | | - Saroj Sinha
- Division of Gastroenterology, Postgraduate Institute of Medical Education and Research, Chandigarh, India
| | - Rajesh Goud
- Asian Institute of Gastroenterology, Hyderabad, India
| | - Vijay K Rai
- Institute of Gastroenterology, Apollo Gleneagles Hospital, Kolkata, India
| | - Manu Tandan
- Asian Institute of Gastroenterology, Hyderabad, India
| | - Rajesh Gupta
- Asian Institute of Gastroenterology, Hyderabad, India
| | - B Joseph Elmunzer
- Division of Gastroenterology and Hepatology, Medical University of South Carolina, Charleston, South Carolina, USA
| | | | - Vivek Kumbhari
- Division of Gastroenterology, Johns Hopkins Medical Institutions, Baltimore, Maryland, USA
| | - Mouen A Khashab
- Division of Gastroenterology, Johns Hopkins Medical Institutions, Baltimore, Maryland, USA
| | - Anthony N Kalloo
- Division of Gastroenterology, Johns Hopkins Medical Institutions, Baltimore, Maryland, USA
| | | | - Vikesh K Singh
- Division of Gastroenterology, Johns Hopkins Medical Institutions, Baltimore, Maryland, USA
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Abstract
PURPOSE OF REVIEW Endoscopic retrograde cholangiopancreatography (ERCP) is a commonly performed procedure to manage pancreaticobiliary disease. Post-ERCP pancreatitis (PEP) is the most common adverse event of ERCP with a significant burden of morbidity and cost. RECENT FINDINGS Appropriate indication and counseling is mandatory especially for patients at increased risk for PEP such as those with suspected sphincter of Oddi dysfunction, pancreatic indications, and a prior history of PEP. Guidewire-facilitated deep cannulation is favored over contrast injection. High-quality trials support the use of rectal administered non-steroidal anti-inflammatory agents and pancreatic duct stent placement for high-risk patients. There is emerging evidence favoring the use of rectal NSAIDs and aggressive hydration in average-risk patients though further studies are required. There is also growing interest in the use of combination therapies as well such as pancreatic stents in combination with NSAIDs. The initial step towards PEP prevention involves careful patient selection and informed decision-making. Endoscopists should use several approaches to mitigate the risk of PEP, including guidewire-assisted cannulation, pancreatic stent placement, and rectal NSAIDs use for high-risk patients. The exact role of aggressive hydration and combination therapies needs to be further investigated.
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Affiliation(s)
- Han Zhang
- Department of Medicine, Division of Gastroenterology, Keck School of Medicine, University of Southern California, D & T Building Room B4H100, 1983 Marengo St, Los Angeles, CA, 90033-1370, USA
| | - Jaehoon Cho
- Department of Medicine, Division of Gastroenterology, Keck School of Medicine, University of Southern California, D & T Building Room B4H100, 1983 Marengo St, Los Angeles, CA, 90033-1370, USA
| | - James Buxbaum
- Department of Medicine, Division of Gastroenterology, Keck School of Medicine, University of Southern California, D & T Building Room B4H100, 1983 Marengo St, Los Angeles, CA, 90033-1370, USA.
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Lyu Y, Cheng Y, Wang B, Xu Y, Du W. What is impact of nonsteroidal anti-inflammatory drugs in the prevention of post-endoscopic retrograde cholangiopancreatography pancreatitis: a meta-analysis of randomized controlled trials. BMC Gastroenterol 2018; 18:106. [PMID: 29973142 PMCID: PMC6032784 DOI: 10.1186/s12876-018-0837-4] [Citation(s) in RCA: 32] [Impact Index Per Article: 4.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/20/2017] [Accepted: 06/26/2018] [Indexed: 12/16/2022] Open
Abstract
Background Recently, although studies have investigated the role of NSAIDs in the prevention of post-endoscopic retrograde cholangiopancreatography pancreatitis (PEP), selection of the ideal drug, the time and route of its administration for the appropriate population remain controversial. Methods A systematic search was done in sources including PubMed, Embase, Web of Science, the Cochrane Library Central, and ClinicalTrials.gov from from August 1, 1990 to August 1, 2017. Randomized controlled trials comparing the prophylactic use of NSAIDs versus a placebo were included. Statistical analysis was performed using the RevMan 5.3 software to assess the outcomes. Results A total of 21 randomized controlled trials were included in the meta-analysis. Our study showed that NSAIDs significantly reduced the incidence of PEP (RR, 0.61, 95%CI,0.52–0.72; p < 0.00001). The analysis showed that indomethacin administration post-ERCP (RR, 0.47; 95% CI, 0.31–0.70; p = 0.0002) appeared to be more effective in preventing PEP than indomethacin administration pre-ERCP (RR, 0.59; 95% CI, 0.45–0.79; P = 0.0003), but there was no significant difference between the high-risk and average-risk population(p = 0.13). In the diclofenac group, it was noted that administration of diclofenac pre-ERCP (RR, 0.32; 95% CI, 0.16–0.63; p = 0.001) was more effective than that in post-ERCP (RR, 0.65; 95% CI, 0.27–1.599; p = 0.35). The relative risk of PEP was 0.63 (95% CI, 0.27–1.50; p = 0.30) in high-risk patients and 0.41 (95% CI, 0.17–0.98; p = 0.02) in average-risk patients. With regard to the route of administration, PEP decreased significantly only in patients receiving the drug rectally (RR, 0.53; 95% CI, 0.44–0.63; p < 0.00001), but not for those who received intramuscularly (RR, 0.74; 95% CI, 0.47–1.17; p = 0.20), intravenously (RR, 0.97; 95% CI, 0.51–1.83; p = 0.93), and orally (RR = 0.88; 95% CI, 0.55–0.1.43; p = 0.62). Conclusions Rectal administration of NSAIDs (both indomethacin and diclofenac) was effective in preventing PEP in unselected patients. A single dose of indomethacin after ERCP might be effective in preventing PEP in both high-risk and average-risk patients. However, diclofenac administered rectally before ERCP might be protective against PEP in high-risk patients compared to a placebo. However, more high quality head-to-head RCTs are required.
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Affiliation(s)
- Yunxiao Lyu
- Department of General Surgery, Dongyang people's Hospital, Dongyang, 322100, Zhejiang Province, China.
| | - Yunxiao Cheng
- Department of General Surgery, Dongyang people's Hospital, Dongyang, 322100, Zhejiang Province, China
| | - Bin Wang
- Department of General Surgery, Dongyang people's Hospital, Dongyang, 322100, Zhejiang Province, China
| | - Yueming Xu
- Department of General Surgery, Dongyang people's Hospital, Dongyang, 322100, Zhejiang Province, China
| | - Weibing Du
- Department of General Surgery, Dongyang people's Hospital, Dongyang, 322100, Zhejiang Province, China
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Mandalia A, Wamsteker EJ, DiMagno MJ. Recent advances in understanding and managing acute pancreatitis. F1000Res 2018; 7. [PMID: 30026919 DOI: 10.12688/f1000research.14244.1] [Citation(s) in RCA: 25] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 06/20/2018] [Indexed: 12/16/2022] Open
Abstract
This review highlights advances made in recent years in the diagnosis and management of acute pancreatitis (AP). We focus on epidemiological, clinical, and management aspects of AP. Additionally, we discuss the role of using risk stratification tools to guide clinical decision making. The majority of patients suffer from mild AP, and only a subset develop moderately severe AP, defined as a pancreatic local complication, or severe AP, defined as persistent organ failure. In mild AP, management typically involves diagnostic evaluation and supportive care resulting usually in a short hospital length of stay (LOS). In severe AP, a multidisciplinary approach is warranted to minimize morbidity and mortality over the course of a protracted hospital LOS. Based on evidence from guideline recommendations, we discuss five treatment interventions, including intravenous fluid resuscitation, feeding, prophylactic antibiotics, probiotics, and timing of endoscopic retrograde cholangiopancreatography (ERCP) in acute biliary pancreatitis. This review also highlights the importance of preventive interventions to reduce hospital readmission or prevent pancreatitis, including alcohol and smoking cessation, same-admission cholecystectomy for acute biliary pancreatitis, and chemoprevention and fluid administration for post-ERCP pancreatitis. Our review aims to consolidate guideline recommendations and high-quality studies published in recent years to guide the management of AP and highlight areas in need of research.
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Affiliation(s)
- Amar Mandalia
- Division of Gastroenterology and Hepatology, University of Michigan School of Medicine, Ann Arbor, MI, 48109, USA
| | - Erik-Jan Wamsteker
- Division of Gastroenterology and Hepatology, University of Michigan School of Medicine, Ann Arbor, MI, 48109, USA
| | - Matthew J DiMagno
- Division of Gastroenterology and Hepatology, University of Michigan School of Medicine, Ann Arbor, MI, 48109, USA
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Abstract
This review highlights advances made in recent years in the diagnosis and management of acute pancreatitis (AP). We focus on epidemiological, clinical, and management aspects of AP. Additionally, we discuss the role of using risk stratification tools to guide clinical decision making. The majority of patients suffer from mild AP, and only a subset develop moderately severe AP, defined as a pancreatic local complication, or severe AP, defined as persistent organ failure. In mild AP, management typically involves diagnostic evaluation and supportive care resulting usually in a short hospital length of stay (LOS). In severe AP, a multidisciplinary approach is warranted to minimize morbidity and mortality over the course of a protracted hospital LOS. Based on evidence from guideline recommendations, we discuss five treatment interventions, including intravenous fluid resuscitation, feeding, prophylactic antibiotics, probiotics, and timing of endoscopic retrograde cholangiopancreatography (ERCP) in acute biliary pancreatitis. This review also highlights the importance of preventive interventions to reduce hospital readmission or prevent pancreatitis, including alcohol and smoking cessation, same-admission cholecystectomy for acute biliary pancreatitis, and chemoprevention and fluid administration for post-ERCP pancreatitis. Our review aims to consolidate guideline recommendations and high-quality studies published in recent years to guide the management of AP and highlight areas in need of research.
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Affiliation(s)
- Amar Mandalia
- Division of Gastroenterology and Hepatology, University of Michigan School of Medicine, Ann Arbor, MI, 48109, USA
| | - Erik-Jan Wamsteker
- Division of Gastroenterology and Hepatology, University of Michigan School of Medicine, Ann Arbor, MI, 48109, USA
| | - Matthew J DiMagno
- Division of Gastroenterology and Hepatology, University of Michigan School of Medicine, Ann Arbor, MI, 48109, USA
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