Acute cholangitis due to common bile duct stones: Clinical outcomes in patients with and without concurrent acute pancreatitis

Abstract

BACKGROUND

Patients with concurrent acute biliary pancreatitis (ABP) and acute cholangitis (AC) may experience exacerbated clinical consequences due to bile duct stones. However, studies exploring this topic remain limited.

AIM

To compare the clinical presentation and outcomes of patients experiencing AC with and without ABP.

METHODS

This single-center retrospective cohort study included 358 patients with AC who underwent endoscopic retrograde cholangiopancreatography (ERCP) between January 2016 and December 2017. Patients were divided into two groups: AC with ABP (n = 90) and AC without ABP (n = 268). Clinical characteristics, laboratory data, ERCP results, primary study outcome [intensive care unit (ICU) admission], and secondary outcomes including 30-day mortality, length of hospital stay, and 30-day readmission rate were analyzed and compared.

RESULTS

All patients in the AC with ABP group had interstitial pancreatitis. The AC with ABP group had significantly higher white cell count (WBC) counts (13.1 × 10³/µL vs 10.4 × 10³/µL, P = 0.007) and more abnormal WBC results (61.1% vs 42.3%, P = 0.015). Liver biochemical tests, AC severity, ERCP success, adverse events, ICU admissions, 30-day mortality, hospital stay, and readmission rates did not differ significantly between the two groups. Univariate analysis showed no significant link between concurrent ABP and ICU admission, although significance was marginal in moderate/severe ABP cases (P = 0.051). In the multivariate analysis, age (P = 0.035) and cardiovascular dysfunction (P < 0.001) were independently associated with length of ICU stay.

CONCLUSION

Concurrent interstitial ABP and AC did not significantly affect outcomes. Age and cardiovascular dysfunction were stronger predictors of ICU admission and should guide clinical monitoring and management.

Key Words: Acute cholangitis; Acute pancreatitis; Atlanta classification; Clinical outcomes; Concurrent; Common bile duct stones; Endoscopic retrograde cholangiopancreatography; Tokyo guidelines

Core Tip: Concurrent acute cholangitis (AC) and acute biliary pancreatitis resulted in significantly higher white cell count (WBC) counts and abnormal WBC counts, suggesting a more intense inflammatory response. However, liver biochemical indices, AC severity, endoscopic retrograde cholangiopancreatography success or adverse events, and primary and secondary outcome measures did not differ significantly between the two groups. Multivariate analysis showed that age and cardiovascular dysfunction were independent factors for intensive care unit admission. Therefore, the presence of acute biliary pancreatitis in patients with AC does not appear to have a significant impact on intensive care unit admission rates or other major clinical outcomes.

INTRODUCTION

Acute cholangitis (AC) occurs when bile duct obstruction leads to cholangio-venous reflux of pathogenic microorganisms or endotoxins with common bile duct stones (CBDS) frequently causing this issue[1]. The pathophysiology of acute biliary pancreatitis (ABP) involves obstruction of the pancreatic duct with gallstones that migrate from the bile duct into the common channel at its opening into the duodenum[2]. Persistent CBDS causes ongoing obstruction of the pancreatic duct and/or biliary tree, potentially resulting in pancreatic necrosis and/or AC[3]. Therefore, some patients with CBDS experience complications from both AC and ABP, which is called gallstone cholangio-pancreatitis[4]. ABP may represent a hybrid condition that encompasses a spectrum ranging from AC with mild acute pancreatitis (biliary-type acute pancreatitis) to necrotizing pancreatitis without biliary involvement (pancreatic-type acute pancreatitis)[1].

AC is uncommon in patients with ABP, accounting for only 2%-3% of patients diagnosed with AC in the early studies or using the Tokyo guidelines (TG18/TG13)[5-7]. There are few studies on the prevalence of ABP in patients with AC caused by CBDS. Currently, only one study has reported the presence of ABP in 23.0% (32/139) of gallstone-related AC cases[8]. The simultaneous presence of ABP may intensify the systemic inflammatory response associated with AC and worsen the clinical course by increasing both morbidity and mortality. Although theoretically interesting most studies have not addressed the clinical impact and outcome of concurrent ABP and AC, resulting in an unknown area in the field of these two diseases[9-11].

Therefore, we hypothesized that the presence of ABP in patients with CBDS-related AC may experience exacerbated disease severity and clinical outcomes such as intensive care unit (ICU) admission, hospital stay, and mortality. Clarifying this association will guide timely clinical triage, urgency of interventions, and arrangement of ICU admission. Therefore, this study was conducted to compare the clinical presentation, endoscopic retrograde cholangiopancreatography (ERCP) treatment, and clinical outcomes in patients with CBDS-related AC with or without ABP.

MATERIALS AND METHODS

This retrospective cohort study was conducted at a tertiary medical center; a flowchart of the study is provided in Figure 1. ERCP remains the first-line approach to treating patients with AC at our institution, after more than two decades.

Figure 1 Study flow chart. ¹According to the 2018/2013 Tokyo guidelines. ABP: Acute biliary pancreatitis; CBDS: Common bile duct stones; ER: Emergency room; ERCP: Endoscopic retrograde cholangiopancreatography.

Definitions in this study

The diagnosis of AC was based on the TG18/TG13 criteria, which included systemic inflammation, cholestasis, and imaging findings. The diagnosis of AC was further categorized as definite AC or suspected AC (Supplementary Table 1)[6]. Systemic inflammation was defined by fever (> 38 °C) or an inflammatory response (WBC < 4000 or > 10000/µL or C-reactive protein ≥ 1 mg/dL). Cholestasis included jaundice (bilirubin ≥ 2 mg/dL) or abnormal liver function tests (alkaline phosphatase, γ-glutamyl transferase, aspartate aminotransferase, or alanine aminotransferase > 1.5 × the upper limit of normal). Imaging findings included bile duct dilatation or evidence of strictures, stones, or stents. According to TG18/13, AC severity was classified as mild, moderate, or severe, with severe AC involving organ dysfunction, including cardiovascular, respiratory, renal, hepatic, or hematological dysfunction (Supplementary Table 2)[6].

The diagnosis and severity of ABP were determined according to the revised Atlanta criteria[2,12]. Supplementary Table 3 Lists the revised diagnostic criteria for acute pancreatitis. Severe ABP was defined as the presence of persistent organ failure (lasting > 48 hours) and/or death. The detailed criteria for severity classification are listed in Supplementary Table 4.

The time to ERCP treatment was defined as the interval between the patient’s arrival at the emergency department and the completion of the ERCP procedure. ERCP-related adverse events, including perforation, pancreatitis, delayed bleeding, and cholangitis, were defined according to the lexicon for endoscopic adverse events published by the American Society for Gastrointestinal Endoscopy[13].

Patient selection

A retrospective review was conducted of 683 patients who underwent ERCP at our center between January 2016 and December 2017 and met the TG18/TG13 criteria for definitive AC[6]. Data were retrieved from the database at the Therapeutic Endoscopy Center[11]. Exclusion criteria included the following: (1) AC caused by factors other than CBDS, such as a previously indwelling biliary stent (n = 61), malignant biliary obstruction (n = 56), or other causes (n = 13); (2) The absence of a native papilla (n = 65); (3) Neither CBDS nor gallstones found on any imaging studies before the ERCP, including abdominal ultrasound, computed tomography (CT) scan, or magnetic resonance cholangiopancreatography (n = 58); and (4) Data lacking on serum amylase or lipase (n = 72).

Data collection

Medical records were reviewed to collect demographic information, including sex and age, clinical manifestations, such as body temperature, systolic blood pressure, heart rate, blood oxygen saturation, respiratory rate, and urine output, and laboratory values, including WBC count, platelet count, prothrombin time-international normalized ratio, and serum levels of creatinine, alanine aminotransferase, aspartate aminotransferase, total bilirubin, alkaline phosphatase, lipase, amylase, and albumin. Gallbladder status (in situ with or without stones or post-cholecystectomy), time to ERCP, and ERCP outcomes, including biliary cannulation success rate, papillary procedures, bile duct clearance (with or without stones), need for stent placement, and adverse events, were also documented. Patient symptoms, vital signs, and laboratory test results used to assess AC severity were collected while patients were in the emergency room. Serum C-reactive protein levels were not collected because C-reactive protein is not a routine test item in the emergency room. Serum albumin level data were available for only 55 patients (12.8%) and were excluded from the analysis.

Outcome assessments

Patients were divided into two groups: AC with ABP, and AC without ABP. The primary outcome comparison was ICU admission. The decision for ICU admission was made by the doctor on duty using the following common criteria: Respiratory failure requiring intubation and an unstable condition despite the use of norepinephrine. Secondary outcomes were 30-day mortality, length of hospital stay (LOHS), and 30-day readmission rate.

Statistical analysis

Continuous variables were presented as medians with interquartile ranges while categorical variables were expressed as numbers and percentages. The Mann-Whitney U test was used for comparisons of continuous variables, and Pearson’s χ² test or Fisher’s exact test was applied to appropriate categorical variables. Logistic regression analysis was conducted to identify factors associated with ICU admissions, with variables having a P value < 0.05 in the univariate analysis included in the multivariate analysis. Results from the univariate and multivariate analyses were reported as odds ratios (ORs) with 95% confidence intervals (CIs). Statistical significance was defined as two-tailed P values < 0.05. All statistical analyses were performed using SPSS software (version 29.0; IBM Corp., Armonk, NY, United States).

RESULTS

This study included a total of 358 patients who met the inclusion criteria. Of these, 90 patients (25.1%) were diagnosed with concurrent ABP and AC. All patients had interstitial edematous pancreatitis on their initial CT scan in the emergency room. This group included 7 patients (7.8%) with severe ABP and 9 patients (10.0%) with moderate ABP. The remaining 268 patients (74.9%) were diagnosed with AC.

Demographic data, clinical characteristics, and laboratory results

Table 1 Lists the patient demographic, laboratory, and clinical characteristics. The median age, sex, and body temperature at onset were comparable between the AC with ABP group and the AC without ABP group. The AC with ABP group had a significantly higher WBC count (13.1 × 10³/µL vs 10.4 × 10³/µL, P = 0.007) and a higher percentage of patients with an abnormal WBC count (61.1% vs 42.3%, P = 0.015). There were no significant differences in any of the liver biochemical tests. Blood cultures were obtained for 293 patients, yielding a positive rate of 19.2% (14/73) in the AC with ABP group and 25.9% (57/220) in the AC without ABP group (P = 0.245).

Table 1 Demographic, laboratory, and clinical characteristics, n (%).

Variables	AC with ABP, n = 90	AC without ABP, n = 268	P value
Age in years	73 (64-82)	63 (52-75)	0.305
Male sex	52 (57.8)	154 (57.5)	0.958
Body temperature in °C	37.4 (36.9-38.0)	37.5 (36.9-38.4)	0.797
WBC count as × 103/µL	13.1 (9.2-17.3)	10.4 (8.5-15.3)	0.007
Abnormal WBC count	55 (61.1)	124 (42.3)	0.015
AST in U/L	178.5 (83-261)	193 (111-468)	0.722
ALT in U/L	175 (89.5-290.5)	222 (136-447)	0.790
ALK-P in U/L	215 (135.5-300.5)	181 (123-267)	0.316
Total bilirubin in mg/dL	3.5 (2.1-5.3)	3.6 (2.5-6.2)	0.795
Creatinine in mg/dL	1.08 (0.90-1.27)	0.88 (0.73-1.15)	0.201
Amylase	1165 (611-2368)	47.6 (40.0-69.4)	< 0.01
Lipase	2054 (1128-4289)	28 (24-40)	< 0.01
Blood culture performed, n = 293	73 (81.1)	220 (82.1)	0.835
Positive blood culture	14/73 (19.2)	57/220 (25.9)	0.245
Gallbladder status
In situ with stone	55 (61.1)	156 (58.2)	0.069
In situ without stone	28 (31.1)	63 (23.5)	0.152
Post cholecystectomy	7 (7.8)	49 (18.3)	0.018
CBDS on images before ERCP	61 (67.8)	171 (63.8)	0.495
Abdominal ultrasound, n = 89	1/19 (5.3)	9/70 (12.9)	0.353
CT scan, n = 356	58/90 (64.4)	154/266 (57.9)	0.274
MRCP, n = 19	3/4 (75)	15/15 (100)	0.047
Median CBDS diameter in mm	5.6 (4.0-8.7)	6.8 (4.7-10.0)	0.775
Severity of AC
Mild	39 (43.3)	141 (52.6)	0.088
Moderate	28 (31.1)	71 (26.5)	0.397
Severe	23 (25.6)	56 (20.9)	0.356
Organ dysfunction
Cardiovascular	4 (4.4)	12 (4.5)	0.989
Neurological	6 (6.7)	14 (5.2)	0.606
Respiratory	6 (6.7)	7 (2.6)	0.075
Renal	11 (12.2)	20 (7.5)	0.165
Hepatic	4 (4.4)	3 (1.1)	0.044
Hematological	8 (8.9)	16 (6.0)	0.352

Data are presented as n (%) or median (interquartile range) unless otherwise defined. ABP: Acute biliary pancreatitis; AC: Acute cholangitis; ALK-P: Alkaline phosphatase; ALT: Alanine aminotransferase; AST: Aspartate aminotransferase; CBDS: Common bile duct stone; ERCP: Endoscopic retrograde cholangiopancreatography; MRCP: Magnetic resonance cholangiopancreatography.

Patients who underwent cholecystectomy before the AC episode were significantly less prevalent in the AC with ABP group than in the AC without ABP group (7.8% vs 18.3%, P = 0.018). Before ERCP, 89 patients (24.9%) underwent transabdominal ultrasonography, 356 patients (99.4%) underwent CT scan, and 19 patients (5.3%) underwent magnetic resonance cholangiopancreatography. CBDS was evident on at least one of these images for 61 patients (67.8%) in the AC with ABP group and 171 patients (63.8%) in the AC without ABP group (P = 0.495). The median stone diameter was 5.6 mm and 6.8 mm in the two groups, respectively (P = 0.775).

There were no significant differences in AC severity and the proportion of organ dysfunction between the AC with ABP and AC without ABP groups.

Outcomes of ERCP

The results of ERCP are listed in Table 2. The time to ERCP treatment in the AC with ABP group was significantly shorter than in the AC without ABP group (median: 45.4 hours vs 62.6 hours, P = 0.030). When stratified by AC severity, the time to ERCP treatment in patients with moderate AC was also significantly shorter in the AC with ABP group (median: 35.9 hours vs 46.6 hours, P = 0.029). However, this difference was not observed in patients with mild or severe AC.

Table 2 Outcomes of endoscopic retrograde cholangiopancreatography, n (%).

Variables	AC with ABP, n = 90	AC without ABP, n = 268	P value
Time to ERCP in hours
Overall population	45.4 (30.4-69.3)	62.6 (26.0-83.1)	0.030
Mild AC	42.1 (18.4-71.8)	46.3 (28.6-84.0)	0.243
Moderate AC	35.9 (19.5-57.6)	46.6 (28.9-76.4)	0.029
Severe AC	63.4 (28.6-91.8)	67.5 (28.8-94.6)	0.538
ERCP procedure
Successful biliary cannulation	90 (100)	264 (98.5)	0.244
Papillary procedures, n = 354
EST	89 (98.9)	253 (94.4)	0.167
EPBD	0	4 (1.5)	0.241
No EST or EPBD	1 (1.1)	10 (3.7)	0.206
Bile duct sweep, n = 341	86 (95.6)	255 (95.1)	0.844
With stones	72/86 (83.7)	230/255 (90.2)	0.103
Without stones	14/86 (16.3)	25/255 (9.8)	0.103
Stent insertion	5 (5.6)	23 (8.6)	0.338
Adverse event due to ERCP	5 (5.6)	14 (5.2)	0.921
Delayed bleeding	2 (2.2)	6 (2.2)	0.982
Pancreatitis	0	6 (1.9)	0.344
AC	2 (2.2)	1 (0.4)	0.159
Perforation	2 (2.2)	1 (0.4)	0.159

Data are presented as n (%) or median (interquartile range) unless otherwise defined. ABP: Acute biliary pancreatitis; AC: Acute cholangitis; EPBD: Endoscopic papillary balloon dilatation; ERCP: Endoscopic retrograde cholangiopancreatography; EST: Endoscopic sphincterotomy.

There was no statistically significant difference in the success rate of deep bile duct cannulation between the two groups (100% vs 98.5%, P = 0.244). Similarly, the frequency of papillary procedures, such as endoscopic sphincterotomy or endoscopic papillary balloon dilatation, did not significantly differ between the groups. Bile duct sweeping was performed in 341 patients: 86 patients (95.6%) in the AC with ABP group and 255 patients (95.1%) in the AC without ABP group (P = 0.844). Among those who underwent bile duct sweeping, stones were removed from 72 patients (83.7%) in the AC with ABP group and 230 patients (90.2%) in the AC without ABP group (P = 0.103).

Plastic stents were placed in 28 patients (7.8%) because of unstable clinical conditions, bile duct stricture (including Mirizzi syndrome), coagulopathy or use of anticoagulants, incomplete stone removal, or significant bleeding after endoscopic sphincterotomy. The incidence of stenting was similar in the two groups. The overall ERCP-related adverse events, including perforation, delayed post-endoscopic sphincterotomy bleeding, biliary tract infection, and pancreatitis, were not significantly different between the two groups (5.6% vs 5.2%, P = 0.921).

Primary and secondary outcomes

Table 3 shows the primary and secondary outcomes for the overall population and for the population when stratified by AC severity. ICU admission rates were similar in the AC with ABP and AC without ABP groups (6.7% vs 4.5%, P = 0.411). Secondary outcomes included 30-day mortality (1.1% vs 0.4%, P = 0.416), LOHS (median: 7 days vs 7 days, P = 0.554), and 30-day readmission rate (8.9% vs 6.7%, P = 0.492), which did not differ significantly between the two groups.

Table 3 Primary and secondary outcomes, n (%).

Variables	AC with ABP, n = 90	AC without ABP, n = 268	P value
Overall population	(n = 90)	(n = 268)
ICU admission	6 (6.7)	12 (4.5)	0.411
30-day mortality	1 (1.1)	1 (0.4%)	0.416
LOHS in days	7.0 (5.5-9.5)	7.0 (5.0-9.0)	0.554
30-day readmission	8 (8.9)	18 (6.7)	0.492
Mild AC	(n = 39)	(n = 141)
ICU admission	0	0
30-day mortality	0	0
LOHS in days	6.0 (5.0-8.0)	6.0 (5.0-8.0)	0.823
30-day readmission	4 (10.2)	5 (3.5)	0.097
Moderate AC	(n = 28)	(n = 71)
ICU admission	0	0
30-day mortality	0	0
LOHS in days	6.0 (5.0-8.5)	6.0 (5.0-9.0)	0.666
30-day readmission	1 (3.6)	7 (9.9)	0.301
Severe AC	(n = 23)	(n = 56)
ICU admission	6 (26.0)	12 (21.4)	0.201
30-day mortality	3 (13.0)	6 (10.7)	0.510
LOHS in days	9.0 (7.0-10.5)	7.5 (6.0-11.0)	0.409
30-day readmission	3 (13.0)	6 (10.7)	0.767

Data are presented as n (%) or median (interquartile range) unless otherwise defined. ABP: Acute biliary pancreatitis; AC: Acute cholangitis; ICU: Intensive care unit; LOHS: Length of hospital stay.

The reasons for readmission within 30 days in the two groups are shown in Table 4. A total of 26 patients (7.3%) were readmitted within 30 days, including 3 cases of acute cholecystitis (0.8%), 3 cases of acute pancreatitis (0.8%), 4 cases of recurrent AC (1.1%), 2 cases of delayed bleeding after endoscopic sphincterotomy (0.6%), 7 cases of planned laparoscopic cholecystectomy (2.0%), and 7 cases of unrelated biliary or pancreatic diseases (2.0%).

Table 4 30-day readmission causes, n (%).

Reason	AC with ABP, n = 90	AC without ABP, n = 268	Overall, n = 358
Acute cholecystitis	1 (1.1)	2 (0.8)	3 (0.8)
Acute pancreatitis	2 (2.2)	1 (0.4)	3 (0.8)
AC	0	4 (1.5)	4 (1.1)
Post-EST bleeding	0	2 (0.8)	2 (0.6)
Scheduled laparoscopic cholecystectomy	3 (3.3)	4 (1.5)	7 (2.0)
Other unrelated disorders	2 (2.2)	5 (1.9)	7 (2.0)

Data are presented as n (%). ABP: Acute biliary pancreatitis; AC: Acute cholangitis; EST: Endoscopic sphincterotomy.

When stratified by AC severity, ICU admission, 30-day mortality, LOHS, and 30-day readmission rates were comparable between the two groups for mild, moderate, and severe disease.

We performed a subgroup analysis restricting ABP to severe or moderate severity, and the results showed that the AC combined with severe/moderate ABP group had a significantly higher ICU admission rate (18.8% vs 4.5%, P = 0.013), a significantly higher 30-day mortality rate (6.3% vs 0.4%), and a significantly longer hospital stay (median, 8.5 days vs 7 days).

Factors associated with ICU admission

Table 5 presents the factors associated with ICU admission. In the univariate analysis, age, sex, WBC count, time to ERCP within 12 hours, any ERCP-related adverse event, and organ failure (including cardiovascular, neurological, or hepatic dysfunction) were associated with ICU admission. Concurrent pancreatitis (OR: 1.524, 95%CI: 0.670-4.186, P = 0.414) was not significantly associated with ICU admission. However, when only severe and moderate ABP cases were considered, this factor showed marginal significance (OR: 5.462, 95%CI: 0.992-30.077, P = 0.051).

Table 5 Univariate and multivariate analyses of factors associated with intensive care unit admission, n (%).

Factor		Univariate analysis		Multivariate analysis
		OR (95%CI)	P value	OR (95%CI)	P value
Age	Every 1-year increase	1.103 (1.050-1.159)	< 0.001	1.179 (1.012-1.373)	0.035
Sex	Male	2.218 (0.839-5.862)	0.108
WBC count		1.148 (0.555-1.230)	< 0.001	1.014 (0.875-1.174)	0.857
Acute pancreatitis	Yes	1.524 (0.670-4.186)	0.414
Severe plus moderate acute pancreatitis	Yes	5.462 (0.992-30.077)	0.051
Time to ERCP within 12 hours	Yes	6.880 (2.211-21.414)	< 0.001	11.984 (0.346-415.629)	0.170
Any ERCP-related AE	Yes	6.133 (1.800-20.897)	0.004	3.123 (0.125-77.908)	0.488
Cardiovascular dysfunction1	Yes	292.067 (62.939-1355.333)	< 0.001	1201.997 (28.078-51457.080)	< 0.001
Neurological dysfunction (conscious disturbance)	Yes	29.909 (9.935-90.038)	< 0.001	28.347 (1.829-439.339)	28.347
Respiratory dysfunction (PaO2/FiO2 ratio < 300)	Yes	Infinite	0.998
Renal dysfunction (Cr > 2.0 mg/dL)	Yes	2.229 (0.608-8.165)	0.226
Hepatic dysfunction (PT-INR > 1.5)	Yes	15.375 (3.135-75.408)	< 0.001	2.443 (0.077-77.235)	0.612
Hematological dysfunction (PLT < 100 × 103/µL)	Yes	3.010 (0.807-11.220)	0.101

¹Cardiovascular dysfunction: Hypotension requiring treatment with dopamine 5 µg/kg per minute, or any dose of norepinephrine.

AE: Adverse event; CI: Confidence interval; Cr: Creatine; ERCP: Endoscopic retrograde cholangiopancreatography; FiO₂: Fraction of inspired oxygen; OR: Odds ratio; PaO₂: Partial pressure of oxygen; PLT: Platelet; PT-INR: Prothrombin time-international normalized ratio.

In the multivariate analysis independent factors associated with ICU admission were age (OR: 1.179, 95%CI: 1.012-1.373, P = 0.035) and cardiovascular dysfunction (OR: 1201.997, 95%CI: 28.078-51457.080, P < 0.001).

DISCUSSION

The diagnosis of AC according to the TG18/TG13 can be divided into definite AC or suspected AC[6]. Using only definite AC diagnostic criteria, we found that 18.7% of patients with AC also had ABP. The inflammation of surrounding tissue due to ABP may theoretically increase the difficulty of ERCP, but there are few studies conducted on this topic[14]. Pecsi et al[14] compared ERCP in patients with ABP and those with AC without ABP. They found no difference in overall biliary cannulation success (95.8% vs 97.2%) or adverse event rates between the two groups. Likewise, in our study the overall success rate of biliary cannulation was comparable in the AC with ABP group and the AC without ABP group (100% vs 98.5%). The overall adverse event rate was also similar (6.7% vs 4.9%).

Pecsi et al[14] reported a higher incidence of normal cholangiograms in patients with ABP compared with patients with AC (20.0% vs 12.3%, P = 0.026). This observation may be due to more frequent spontaneous passage of CBDS into the duodenum before ERCP in patients with ABP[15,16]. However, the direct comparison of the rates of spontaneous CBDS passage in patients with AC alone and patients with both AC and ABP has not been conducted. In our study, the detection rates of CBDS on imaging before ERCP were similar between the two groups and stone retrieval rates via bile duct sweeping during ERCP were also comparable. These findings suggest that the spontaneous CBDS passage rate did not significantly differ between the groups.

Patients with both AC and ABP are expected to exhibit a more pronounced inflammatory response than patients with AC alone. This potentially results in worse clinical outcomes. However, studies specifically investigating this association are lacking. Our patients with AC and ABP demonstrated significantly higher WBC counts and a higher incidence of abnormal WBC values, indicating an enhanced inflammatory response in those with both conditions. Unexpectedly, clinical outcomes, including ICU admission rates, 30-day mortality, LOHS, and 30-day readmission rates, were similar between the two groups.

This discrepancy may lie in the criteria used to classify disease severity. Both the TG18/TG13 and the revised Atlanta criteria rely on the presence of organ failure to define severe illness. Based on the revised Atlanta criteria, severe ABP is defined by the presence of persistent organ failure (lasting > 48 hours) and/or death. Organ failure is defined as shock, pulmonary insufficiency, renal failure, and/or gastrointestinal bleeding or modified Marshall score of 2 or more in the three accepted organ systems. Moderately severe ABP is defined as transient organ failure (resolves within 48 hours) and/or the development of local complications. As a result, we may have categorized patients with severe or moderately severe ABP, even when the ABP was mild.

Another potential explanation is the spontaneous passage of CBDS prior to ERCP, particularly in patients with ABP. Spontaneous passage likely resolves the obstruction. In these cases, the inflammatory response may overestimate the actual severity of ABP, and clinical outcomes remain stable. Furthermore, CT imaging in our cohort did not reveal peripancreatic fluid collections or pancreatic necrosis, suggesting that most cases were mild[1]. Due to the overlap in the severity classification between the TG18/TG13 and Atlanta criteria, the severity of ABP in the patients with both AC and ABP should be assessed dynamically and continuously instead of relying on the Atlanta classification.

The clinical outcomes of concurrent AC and ABP were similar to those of AC alone, suggesting that concurrent AC and ABP can be treated according to the AC management guidelines for ERCP[17,18]. However, the mean time to ERCP treatment was shorter in the AC with ABP group compared with the AC group, particularly among patients with moderate AC. ERCP timing is primarily based on the physician’s discretion based on the patient’s hemodynamic status and clinical condition. Although patients with severe AC experience longer delays before ERCP treatment than patients with moderate or mild AC due to their unstable condition, we found similar times to ERCP between the two groups. Therefore, we believe this factor did not significantly influence the overall study outcomes.

A multicenter study involving 6063 patients from Japan and Taiwan (including our center) divided patients into two groups according to whether they underwent early/urgent ERCP[19]. There was no difference in 30-day mortality between the two groups for patients with mild or severe AC. However, the 30-day mortality was significantly lower in patients with moderate AC who underwent early/urgent ERCP. This suggests that the TG18/TG13 AC severity grading criteria may be more favorable for patients with moderate AC who benefit the most from timely biliary drainage. The report also observed significantly higher 30-day mortality in patients with grade II AC and abnormal WBC counts, suggesting that early ERCP may be particularly beneficial for our patients with AC and ABP with elevated WBC counts. Because the AC with ABP group had a significantly higher rate of abnormal WBC counts (a key criterion for moderate AC), clinicians should prioritize early ERCP treatment in this patient population.

Our study had several limitations. First, the inherent biases of observational and retrospective study designs (e.g., selection bias) should be acknowledged. However, due to the limited number of studies on this topic, our study still provides valuable insights; Second, CT scans were performed while the patient was treated in the emergency room, potentially leading to the underdiagnosis of some patients with moderately severe ABP because signs of impaired pancreatic perfusion and peripancreatic necrosis are not apparent until several days later[12]; Third, albumin data (one criterion for moderate AC) were available in only 12.8% of patients. Therefore, patients with moderate AC may be misclassified as mild AC and vice versa. Fourth, the time to ERCP treatment was longer for patients with severe AC than for patients with moderate or mild AC regardless of the presence of ABP because of the unstable conditions of patients with severe AC. However, we believe this factor did not influence the overall study outcomes because the times were comparable in both groups. In the multivariate analysis, we identified age and cardiovascular dysfunction as independent predictors of ICU admission. Notably, pancreatitis itself was not an independent risk factor for ICU admission, contrasting with our initial hypothesis that concurrent ABP would worsen clinical outcomes. Therefore, risk stratification in AC should incorporate age and cardiovascular dysfunction as well as inflammatory markers and concomitant ABP.

CONCLUSION

This study demonstrated that the presence of interstitial ABP in patients with AC did not significantly impact ICU admission rates or other major outcomes. However, age and cardiovascular dysfunction were critical determinants of ICU admission. The findings highlighted the importance of managing organ dysfunction and monitoring older patients closely.