Journal of. Review Article Volume 2 Issue 5. Incidence rates of post-ERCP complications: a systematic survey of prospective studies. Am J Gastroenterol. Early recognition of post-ERCP pancreatitis by clinical assessment and serum pancreatic enzymes.
Risk factors for pancreatitis following endoscopic retrograde cholangiopancreatography: a meta-analysis. Bradley EL. A clinically based classification system for acute pancreatitis. Arch Surg. Patterns of use of endoscopic retro-grade cholangiopancreatography in a Canadian province. Can J Gastroenterol. Quality indicators, including complications, of ERCP in a community setting: a prospective study. Gastrointest Endosc.
Risk factors for complication following ERCP; results of a large-scale, prospective multicenter study. A randomized trial of rectal indomethacin to prevent post-ERCP pancreatitis. N Engl J Med. Rectal indomethacin does not prevent post-ERCP pancreatitis in consecutive patients. Complications of ERCP. Routine pre-procedural rectal indometacin versus selective post-procedural rectal indometacin to prevent pancreatitis in patients undergoing endoscopic retrograde cholangiopancreatography: a multicentre, single-blinded, randomised controlled trial.
Effect of body weight on fixed dose of diclofenac for the prevention of post-endoscopic retrograde cholangiopancreatography pancreatitis. Scand J Gastroenterol. Ulinastatin shows preventive effect on post-endoscopic retrograde cholangiopancreatography pancreatitis in a multicenter prospective randomized study. J Gastroenterol Hepatol. Ulinastatin for pancreatitis after endoscopic retrograde cholangiopancreatography: a randomized, controlled trial.
Clin Gastroenterol Hepatol. Aliment Pharmacol Ther. Nitroglycerin in the prevention of post-ERCP pancreatitis: a meta-analysis. Dig Dis Sci. Meta-analysis: somatostatin or its long-acting analogue, octreotide, for prophylaxis against post-ERCP pancreatitis.
J Gastroenterol. Aggressive hydration with Lactated Ringer's solution as the prophylactic intervention for postendoscopic retrograde cholangiopancreatographypancreatitis: A randomized controlled double blind clinical trial.
J Res Med Sci. Biliary cannulation during endoscopic retrograde cholangiopancreatography: core technique and recent innovations. Needle-knife sphincterotomy: factors predicting its use and the relationship with post-ERCP pancreatitis with video. Can wire-guided cannulation prevent post-ERCP pancreatitis? A prospective randomized trial. Guidewire cannulation reduces risk of post-ERCP pancreatitis and facilitates bile duct cannulation.
The American Journal of Gastroenterology. Endoscopic sphincterotomy is a common cause of pancreatitis after ERCP. This procedure is typically performed during an ERCP procedure after a diagnosis is made. Endoscopic sphincterotomy involves several types of instruments being inserted through the endoscope, or tube-like instrument, that is inserted during ERCP.
The sphincter, or group of muscles that controls the flow of pancreatic fluid and bile, is cut or stretched. This allows the removal of stones. A stent, or drain, may be inserted to prevent the narrowed region from returning to its narrowed state. Patients may be more likely to develop pancreatitis after ERCP if they:. Dugdale, David, ed. Flati, Giancarlo, et al. Lehman, Glen A. A proposed alternative to the consensus definition is the standard clinical definition of acute pancreatitis, which mandates presence of 2 of the 3 following features: 1 abdominal pain typical of acute pancreatitis; 2 at least a 3-fold elevation in serum amylase or lipase levels; and 3 evidence of pancreatitic inflammation on cross-sectional imaging A prospective comparative study demonstrated that the clinical definition is more sensitive than the consensus definition, 9 however the clinical impact of this more sensitive diagnostic approach — which may only capture additional mild self-limited cases — is unclear.
Further, the radiation exposure and costs of systematic CT scanning in all patients with post-ERCP pain are not justified. Given the limitations of both definitions, additional research aiming to elucidate a practical and accurate diagnostic tool for PEP is of substantial importance. Ideally, this tool would be objective, applicable early in the course of disease, and would reliably diagnose patients destined to develop a clinically important adverse course, in whom hospitalization and other interventions is likely to be beneficial.
Our understanding of the mechanisms underlying PEP has evolved slowly and remains limited. As the only true human model for the study of acute pancreatitis, fully elucidating the pathophysiology of PEP is of substantial importance, not only to guide the development of novel pharmacologic interventions, but also to expand our understanding of pancreatitis in general.
This initial injury leads to premature intra-pancreatic activation of trypsinogen , which — in patients with genetic or environmental predisposition — incites the inflammatory cascade. The relative contribution of each of the aforementioned injurious factors remains unclear and is probably variable, but no single factor appears dominant.
Thus a multifactorial approach involving several complimentary pharmacologic and mechanical prophylactic measures addressing different mechanisms of injury may be the most effective approach to PEP prevention. Alternatively, interventions that impact downstream inflammatory targets e.
A principal objective of an upcoming large-scale comparative effectiveness trial of indomethacin and prophylactic stent placement is to develop a robust repository of biological specimens from study participants to drive translational research elucidating the pathophysiology of PEP and pancreatitis in general.
Preventive strategies can be broadly divided into 5 areas: 1 appropriate patient selection, 2 risk stratification of patients undergoing ERCP and meaningful use of this information in clinical decision-making, 3 atraumatic and efficient procedural technique, 4 prophylactic pancreatic stent placement, and 5 pharmacoprevention.
All five strategy areas should be considered in every case, and the latter two implemented when appropriate. Additionally, EUS, MRI, and other non-invasive modalities such as radionucleotide-labeled scan and percutaneous drain fluid analysis are very accurate in diagnosing a multitude of other pancreaticobiliary processes e.
Indeed, the utilization of ERCP as a diagnostic procedure has steadily declined in favor of less invasive but equally accurate alternative tests, and ERCP has appropriately become a near-exclusively therapeutic procedure reserved for patients with a high pre-test probability of intervention 93, This trend is consistent with recent clinical practice guidelines on the role of endoscopy in the evaluation of choledocholithiasis and the National Institutes of Health consensus statement on ERCP for diagnosis and therapy, both favoring less invasive tests over ERCP in the diagnosis of biliary disease 2, An exception to the widespread practice of reserving ERCP for patients with a high likelihood of therapeutic intervention has been the evaluation of patients with suspected sphincter of oddi dysfunction SOD , for which an accurate, less-invasive alternative to ERCP-guided sphincter of Oddi manometry SOM remains elusive 40, Even when considering patients for SOM, however, thoughtful clinical judgment is necessary to select those who are most likely to benefit from the procedure.
Additional studies are necessary to determine whether diagnostic ERCP with SOM is truly beneficial in cases of suspected type 2 biliary or pancreatic SOD recurrent unexplained pancreatitis.
Pending such studies, many experts believe ERCP remains reasonable in such cases after careful assessment of the risk-benefit ratio and detailed informed consent. Another possible exception to the therapeutic ERCP trend may be the evaluation of biliary complications in liver transplant recipients, for whom a recent retrospective study suggested that diagnostic ERCP is a reasonable and efficient clinical approach in this patient population based on a high likelihood of therapeutic intervention and a very low rate of complications, in particular PEP A substantial amount of research over the last two decades has contributed to our understanding of the independent risk factors for post-ERCP pancreatitis.
These risk factors can be divided into patient-related and procedure-related characteristics. The definite and probable patient-related risk factors that predispose to PEP are: a clinical suspicion of sphincter of SOD regardless of whether or not sphincter of Oddi manometry is performed 35, 53, 56, 58, 87, 89, , a history of prior PEP 27, 56, 59, , a history of recurrent pancreatitis 89 , normal bilirubin 56, 94 , younger age, 27, 85, 90, and female gender 56, 89, The definite and probable procedure-related risk factors for PEP are: difficult cannulation 56, 58, , pancreatic sphincterotomy 27, 56 , ampullectomy 46, , repeated or aggressive pancreatography 56, 58, 85, 89 , and short-duration balloon dilation of an intact biliary sphincter 15, 44, Two recent systematic reviews have affirmed that most of these factors are independently associated with PEP 26, Additional risk factors that have been implicated, but are not concretely accepted as independent predictors of PEP are precut access sphincterotomy see below 58, 89, , pancreatic duct wire passage see below , biliary sphincterotomy, self-expanding metal stent placement, non-dilated bile duct, intraductal papillary mucinous neoplasm, and Billroth 2 anatomy.
Operator endoscopist -dependent characteristics have also been implicated in the risk of PEP. Endoscopist procedure volume is suggested to be a risk factor for PEP, although multi-center studies have not confirmed this trend, presumably because low-volume endoscopists tend to perform lower-risk cases 56, 58, 85, Nevertheless, potentially dangerous cases based on either patient-related factors or anticipated high-risk interventions are best referred to expert medical centers where a high-volume endoscopist with expertise in prophylactic pancreatic stent placement can perform the case, and where more experience with rescue from serious complications may improve clinical outcomes 64, Similarly, trainee involvement in ERCP is a possible independent risk factor for PEP, although results of existing multivariable analyses are conflicting 27, It stands to reason that inexperienced trainees may augment procedure-related risk factors, such as prolonging a difficult cannulation or delivering excess electrosurgical current during an inefficient pancreatic sphicterotomy, etc.
Therefore, an improved understanding of the process of ERCP training is necessary to minimize the contribution of trainee involvement to the development of PEP. Future research focused on defining ERCP training metrics and developing an evidence-based list of appropriate fellow cases based on stage of training and skill level is needed. Further, defining the optimal parameters that guide trainee-attending scope exchange during any particular case or intervention is necessary in order to maximize learning potential while minimizing patient risk.
Several additional points regarding clinical risk stratification are worth considering. First, predictors of PEP appear synergistic in nature For example, a widely referenced multi-center study by Freeman et al.
Second, patients with a clinical suspicion of SOD, particularly women, are not only at increased risk for PEP in general, but appear more likely to develop severe pancreatitis and death 56, 58, Additionally, several clinical characteristics are thought to significantly reduce the risk of PEP.
First, biliary interventions in patients with a pre-existing biliary sphincterotomy probably confer a very low risk of PEP. Prior sphincterotomy will have generally separated the biliary and pancreatic orifices, allowing avoidance of the pancreas, and making pancreatic sphincter or duct trauma unlikely. Further, patients with chronic pancreatitis, in particular those with calcific pancreatitis, are at low risk for PEP because of gland atrophy, fibrosis, and consequent decrease in exocrine enzymatic activity Similarly, the progressive decline in pancreatic exocrine function associated with aging may protect older patients from pancreatic injury Lastly, perhaps due to post-obstructive parenchymal atrophy, patients with pancreatic head malignancy appear to be relatively protected as well While understanding these aforementioned risk factors and incorporating them into clinical decision-making are important aspects of preventing PEP, additional research focused on developing more robust risk-stratification tools based upon existing literature and future multi-center studies is important.
Such risk stratification instruments are unlikely to be developed using conventional statistical models ie; multivariable regression analysis , and may require the use of novel, more advanced prediction methods involving artificial intelligence, such as machine learning — a technique that has already been successfully utilized in both business and medicine Meaningful Use of Risk-Stratification Information. Armed with risk assessment information, clinicians can better inform patients about adverse events and tailor costly and potentially dangerous risk-reducing strategies.
For example, prophylactic pancreatic stent placement and consideration of post-procedure hospital observation are appropriate for a patient predicted to be at high risk for PEP, but are not justified in low-risk cases.
Patient-related characteristics are not modifiable, but can be used at least in part to predict the risk of PEP prior to ERCP, allowing appropriate case selection and a meaningful discussion with the patient regarding the risk-benefit ratio of the procedure.
For example, a young woman with suspected biliary SOD but moderate symptoms that are partially responsive to pain modulating therapy may elect to forgo ERCP after understanding her elevated risk of severe PEP. Indeed, the ability to risk-stratify patients can concretely influence the decision-making process that surrounds 1 proceeding with ERCP, 2 referral to a tertiary center, 3 fluid resuscitation, 4 prophylactic stent placement, 5 pharmacoprevention, and 6 post-procedural hospital observation.
Efficient and atraumatic technical practices during ERCP are central to minimizing the risk of pancreatitis. Many of the procedure-related risk factors listed above, while predisposing to PEP, are mandatory elements of a successful case. Even though these high-risk interventions are unavoidable for execution of the clinical objective, certain strategies can be utilized to minimize procedure-related risk.
As mentioned, difficult cannulation and pancreatic duct injection are both independent risk factors for PEP. As such, interventions that improve the efficiency of cannulation and limit injection of contrast into the pancreas are likely to decrease the risk of pancreatitis.
Guidewire-assisted cannulation accomplishes both, representing a major paradigm shift in ERCP practice. In contrast to conventional contrast-assisted cannulation, which may lead to inadvertent injection of the pancreatic duct or contribute to papillary edema, guidewire-assisted cannulation employs a small-diameter wire with a hydrophilic tip that is initially advanced into the duct, subsequently guiding passage of the catheter.
Since the wire is thinner and more maneuverable than the cannula, it is easier to advance across a potentially narrow and off-angle orifice. Moreover, this process limits the likelihood of an inadvertent pancreatic or intramural papillary injection.
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