Acute gallstone pancreatitis (AGP) is the most common cause of acute pancreatitis (AP) in the United States. Patients with AGP may also present with choledocholithiasis. In 2010, the American Society for Gastrointestinal Endoscopy (ASGE) suggested a management algorithm based on probability for choledocholithiasis, recommending additional imaging for patients at intermediate risk and endoscopic retrograde cholangiopancreatography (ERCP) for patients at high risk of choledocholithiasis. In 2019, the ASGE guidelines were updated using more specific criteria to categorize individuals at high risk for choledocholithiasis. Neither ASGE guideline has been studied in AGP to determine the probability of having choledocholithiasis.

To determine compliance with ASGE guidelines, assess outcomes, and compare 2019 vs 2010 ASGE criteria for suspected choledocholithiasis in AGP.

We conducted a retrospective cohort study of 882 patients admitted with AP to a single tertiary care center from 2008-2018. AP was diagnosed using revised Atlanta criteria and AGP was defined as the presence of gallstones on imaging or with cholestatic pattern of liver injury in the absence of another cause. Patients with chronic pancreatitis and pancreatic malignancy were excluded as were those who went directly to cholecystectomy prior to assessment for choledocholithiasis. Patients were assigned low, intermediate or high risk based on ASGE guidelines. Our primary outcomes of interest were the proportion of patients in the intermediate risk group undergoing magnetic resonance cholangiopancreatography (MRCP) first and the proportion of patients in the high risk group undergoing ERCP directly without preceding imaging. Secondary outcomes of interest included outcome differences based on if guidelines were not adhered to. We then evaluated the diagnostic accuracy of 2019 in comparison to the 2010 ASGE criteria for patients with suspected choledocholithiasis. We performed the t test or Wilcoxon rank sum test, as appropriate, to analyze if there were outcome differences based on if guidelines were not adhered to. Kappa coefficients were calculated to measure the degree of agreement between pairs of variables.

In this cohort, we identified 235 patients with AGP of which 79 patients were excluded as they went directly to surgery for cholecystectomy without prior MRCP or ERCP. Of the remaining 156 patients, 79 patients were categorized as intermediate risk and 77 patients were high risk for choledocholithiasis according to the 2010 ASGE guidelines. Among 79 intermediate risk patients, 54 (68%) underwent MRCP first whereas 25 patients (32%) went directly to ERCP. For the 54 patients with intermediate risk who had MRCP first, 36 patients had no choledocholithiasis while 18 patients had evidence of choledocholithiasis prompting ERCP. Of these patients, ERCP confirmed stone disease in 11 patients. Of the 25 intermediate risk patients who directly underwent ERCP, 18 patients had stone disease. One patient with a normal ERCP developed post ERCP pancreatitis. Patients undergoing MRCP in this group had a significantly longer length of stay (5.0 vs 4.0 d, P = 0.02). In the high risk group, 64 patients (83%) had ERCP without preceding imaging, of which, 53 patients had findings consistent with choledocholithiasis, of which 13 patients (17%) underwent MRCP before ERCP, all of which showed evidence of stone disease. Furthermore, all of these patients ultimately had an ERCP, of which 8 patients had evidence of stones and 5 had normal examination.

Our cohort also demonstrated that 58% of all 156 patients with AGP had confirmed choledocholithiasis (79% of the high risk group and 37% of the intermediate group when risk was assigned based on the 2010 ASGE guidelines). When the updated 2019 ASGE guidelines were applied instead of the original 2010 guidelines, there was moderate agreement between the 2010 and 2019 guidelines (kappa = 0.46, 95%CI: 0.34-0.58). Forty-two of 77 patients were still deemed to be high risk and 35 patients were downgraded to intermediate risk. Thirty-five patients who were originally assigned high risk were reclassified as intermediate risk. For these 35 patients, 26 patients had ERCP findings consistent with choledocholithiasis and 9 patients had a normal examination. Based on the 2019 criteria, 9/35 patients who were downgraded to intermediate risk had an unnecessary ERCP with normal findings (without a preceding MRCP).

Two-thirds in intermediate risk and 83% in high risk group followed ASGE guidelines for choledocholithiasis. One intermediate-group patient with normal ERCP had post-ERCP AP, highlighting the risk of unnecessary procedures.

Acute gallstone pancreatitis (AGP) is the most common cause of acute pancreatitis (AP) in the United States[1]. Patients with AGP may also present with choledocholithiasis as the occurrence of common bile duct (CBD) stones is present in up to 15% of patients with gallstones[2]. The diagnosis of choledocholithiasis is challenging and requires a high degree of suspicion as it often cannot be made conclusively without invasive procedures like endoscopic retrograde cholangiopancreatography (ERCP)[3]. In 2010, the American Society for Gastrointestinal Endoscopy (ASGE) suggested a management algorithm based on probability for choledocholithiasis to assist in risk stratifying patients[4]. These guidelines stratify patients into those with high, intermediate, and low risk based on clinical criteria, liver tests, and abdominal ultrasound. High risk (> 50% probability of choledocholithiasis) is defined as the presence of any very strong predictor (clinical ascending cholangitis, CBD stone seen on ultrasound, and/or total bilirubin > 4 mg/dL) or the presence of both strong predictors (CBD dilated more than 6 mm and bilirubin 1.8-4 mg/dL). Intermediate risk (10%-50% probability of choledocholithiasis) is defined as presence of age > 55, clinical gallstone pancreatitis, any other abnormal liver test. Finally, low risk patients do not have any of these features[4].

These guidelines aim to provide evidence-based recommendations with the goal of optimizing the efficacy and safety of patient care by minimizing the morbidity and cost from unnecessary invasive biliary evaluation. Furthermore, they recommend imaging [i.e. magnetic resonance cholangiopancreatography (MRCP) or endoscopic ultrasound (EUS)] for patients with intermediate risk and ERCP for patients with high probability of choledocholithiasis[4].

In 2019, the ASGE guidelines were updated using more specific criteria to categorize individuals at high-risk for choledocholithiasis[5]. These updated criteria propose that high-risk patients are those with elevated total bilirubin > 4 mg/dL and dilated CBD. The presence of only elevated total bilirubin > 4 or total bilirubin 1.8-4 with dilated CBD are no longer in the criteria for the high-risk group. These guidelines still recommend ERCP for those with high risk and imaging (MRCP or EUS) for those with intermediate risk for choledocholithiasis[6]. Additionally, clinical gallstone pancreatitis was removed as one of the criteria for assigning intermediate risk[6].

Neither ASGE guideline has been studied in AGP to determine the probability of having choledocholithiasis. Thus, our study aimed to determine the true incidence of choledocholithiasis in patients with AGP and determine compliance with the guidelines at our institution and assess outcomes when guidelines were not adhered to. In our patient population of AGP, we also evaluated the performance and diagnostic accuracy of 2019 vs 2010 ASGE criteria for suspected choledocholithiasis in patients with AGP.

AGP is the most common cause of AP in the United States accounting for approximately one-third of all cases[1]. Furthermore, given the potential for comorbid choledocholithiasis, patients with AGP should be evaluated for CBD stone disease[2]. In our cohort of patients with AGP, 37% of patients with intermediate risk and 79.2% of patients with high risk for choledocholithiasis based on the 2010 ASGE guidelines had documented CBD stone disease. When combined, our data demonstrated that the true incidence of choledocholithiasis in patients with AGP is 58%. The overall high prevalence of concurrent choledocholithiasis in patients with AGP may help explain the relatively high risk of recurrent pancreatitis in patients with AGP[10].

The ASGE published guidelines in 2010 which proposed a risk stratification system to clarify how to best manage patients with suspected choledocholithiasis, categorizing patients into low, intermediate and high risk[4].

In this scheme, patients at high risk are recommended to undergo ERCP directly without further imaging and those at intermediate risk should have additional imaging with MRCP or EUS. Those at low risk require no further evaluation. In this study, we aimed to apply these guidelines to patients admitted with AGP to a single tertiary care center over 10 years and determine what effect deviation had on outcomes.

In our cohort of 156 patients, approximately one-half of patients were either classified as intermediate or high risk. Since all patients in our cohort had AGP and the presence of AGP was a criteria for at least intermediate risk for choledocholithiasis according to the 2010 ASGE guidelines, no patients in our cohort were considered low risk for choledocholithiasis. After applying the guidelines to these groups, 76% of patients (54 patients in the intermediate group and 64 patients in the high risk group) were managed in accordance to the ASGE recommendations and 24% of patients (25 patients in the intermediate group and 13 patients in the high risk group) deviated from the guidelines. Specifically in the intermediate group, 7 patients who had an ERCP first had a normal examination suggesting that an inappropriate procedure was performed and importantly, one of these patients suffered from post-ERCP pancreatitis. These 7 intermediate risk patents who directly underwent ERCP and had normal findings did not receive EUS or MRCP. Thus, it may be prudent to consider EUS to evaluate for choledocholithiasis to prevent unnecessary ERCPs. Furthermore, all 13 of the patients in the high risk group who underwent MRCP prior to ERCP had a positive finding, suggesting an unnecessary test (i.e. MRCP) was performed first. Importantly, patients who underwent MRCP prior to ERCP were found to have longer hospital lengths of stay and delays in initiation of enteral feeding.

The ASGE guidelines provide evidence-based recommendations with the goal of optimizing the efficacy and safety of patient care. Additionally, a study has shown that adherence to ASGE guidelines also result in cost-saving from unnecessary imaging studies[3]. Accordingly, patients with intermediate risk (10%-50%) should undergo additional imaging because the risk of choledocholithiasis is too low to warrant proceeding directly to ERCP[6]. MRCP is often preferred in patients with pancreatitis who have intermediate risk for choledocholithiasis because it has high sensitivity in detecting CBD stones without procedural risks[11]. While ERCP is highly sensitive and specific in diagnosis and effective in therapeutic management of choledocholithiasis[12], the procedure also has a number of associated risks such as post-ERCP pancreatitis and post-endoscopic sphincterotomy bleeding[13,14]. One of the intermediate risk patients in our cohort who went directly to ERCP which showed normal findings developed worsening of pancreatitis thought to be related to post ERCP AP. This highlights that unnecessary invasive procedure and adverse outcome could have been prevented by adhering to the guidelines.

In 2019, the ASGE updated guidelines on management of choledocholithiasis, which further fine-tuned the criteria needed for the high risk group[6]. Specifically, patients now required the presence of a bilirubin greater than 4 mg/dL and imaging with a dilated CBD to qualify as high risk and thus those patients with a total bilirubin of 1.8-4.0 mg/dL with CBD dilation on imaging were downgraded to intermediate risk. The impetus for these changes were largely driven by studies that demonstrated that up to 30% of patients had ERCPs without evidence of CBD stones[15,16]. In our study, we found that approximately 26% (9/35) of patients categorized as high risk by 2019 criteria had a normal ERCP.

Since the cohort we studied was prior to the update, the 2010 guidelines were used in the initial analysis. In our subsequent analysis we aimed to determine concordance in categorization between the 2010 and 2019 guidelines. After applying the 2019 guidelines, we found that all patients in the intermediate group remained the intermediate group, whereas there was less concordance in the high risk group which was largely due to the group of patients who had lower total bilirubin levels. Importantly, using the newer guidelines, 9 patients may have been spared an ERCP. We also found that while the 2010 ASGE guidelines in predicting high risk for choledocholithiasis had a specificity of 75.8%, using the 2019 ASGE guidelines led to an improved specificity of 89.4%. This demonstrated that the use of the revised guidelines in assessing risk for choledocholithiasis in AGP patients can lead to a decrease in unnecessary invasive and costly procedures. Moreover, although AGP was removed from the intermediate risk criteria, all patients in our intermediate cohort remained intermediate suggesting that AGP implicitly increases the risk to the intermediate level for choledocholithiasis. This was verified in our cohort where 58% of patients with AGP were confirmed to have choledocholithiasis. Thus, clinicians should remain vigilant for concurrent choledocholithiasis in patients admitted with AGP.

We recognize that our study also has several limitations. First, this is a retrospective cohort study which has a potential for selection bias. The smaller size and retrospective nature of this study may limit the assessment of the degree of adherence to the ASGE guidelines. As the decision to proceed with MRCP or ERCP were at the discretion of the physician on service, the detailed reasoning behind selecting each modality was not always apparent in the medical record. Our results may not be generalizable to all medical settings as this study was done at a single tertiary care center at an academic institution located in a large metropolitan city. Further work is needed to determine the influencing factors driving deviation from the guidelines.

In the study cohort, we demonstrated that more than half of patients with AGP have choledocholithiasis. We also found that approximately two thirds of patients in the intermediate group and 83% of patients in the high risk group followed ASGE guidelines for management of choledocholithiasis in the setting of AGP. There was associated longer LOS for patients undergoing MRCP in both groups. Importantly, one patient who had a normal ERCP in the intermediate group without preceding MRCP suffered from post ERCP AP, highlighting the risk of unnecessary procedures. Further work is needed to determine the influencing factors driving deviation from the guidelines.

The authors would like to thank the Harvard Catalyst Biostatistics Consulting Program at Beth Israel Deaconess Medical Center for reviewing statistical methods and reporting of results.