Clinical Case Summary

We collected clinical, laboratory, radiological, cholangiographic, endoscopic and pathological findings from a 58 years old male, obese, with type 2 diabetes and with cardiovascular comorbidity. During 2020-2021, he was admitted several times at the Emergency Department for abdominal and thoracic pain, nausea and cold sweating, with night onset. Radiological, including abdominal Computed Tomography (CT) and laboratoristic findings were persistently negative. In 2022 he was hospitalized for acute mild biliopancreatitis. Abdominal Ultrasound (US) resulted negative for bile duct dilatation. During hospitalization, symptomatology improved, but he developed jaundice. Abdominal CT with contrast medium was performed, confirming mild pancreatitis (CT Severity Index 2), thickening and hyperemia of the common bile duct wall. Magnetic Resonance Cholangiopancreatography (MRCP) showed cholelithiasis, choledocolithiasis with multiple chained filling defects, without bile ducts dilatation. Endoscopic Retrograde CholangioPancreatography (ERCP) was then performed, demonstrating a 2 cm filling defect, with extraction of mucus and sludge, mixed with intraluminal tissue. Histopathology described a Bile Duct Intraductal Papillary Mucinous Neoplasm (IPMN-B) with low grade (and focally high grade) dysplasia. Clinical onset and imaging were misleading and ERCP findings were unexpected. IPMN-B is a rare premalignant disease, presenting as an intraluminal papillary mass, sometimes secreting mucus, and leading to abdominal pain, obstructive jaundice and cholangitis. Associated lithiasis is not rare and can be confusing. Pathological and radiological classification have been proposed. Here we focus on clinical presentation and radiological appearance aiming to raise the awareness about this rare entity.

References

1. Endoscopic image showing mucus and sludge, mixed with friable tissue, draining from papilla maior
2. Magnetic Resonance Cholangiopancreatography demonstrating focal lack of signal in common bile duct
3. Retrograde Cholangiogram showing a “peculiar” filling defect in a fusiform dilated choledocus

Introduction

Endoscopic retrograde cholangiopancreatography (ERCP) is a cornerstone in the diagnosis and treatment of pancreatobiliary diseases. However, it carries the risk of complications including potentially fatal post-ERCP pancreatitis (PEP). Despite ongoing efforts, effective strategies for managing PEP remain unestablished. Current guidelines define PEP based on symptoms and findings occurring within 24 hours after ERCP; however, early diagnosis and intervention may prevent its incidence and severity. Recently, urinary trypsinogen-2 (UT2) has emerged as a potential biomarker for early acute pancreatitis, but its role and the optimal timing for PEP remain unclear. Therefore, we aimed to evaluate the diagnostic performance of UT2 at multiple time points following ERCP.

Aims & Methods

This is a single-center prospective observational study conducted at The University of Tokyo Hospital. Patients who underwent their initial ERCP at our institution between February 2022 and June 2024 were enrolled. Patients with choledochojejunostomy, biliary pancreatitis, or those undergoing hemodialysis were excluded. UT2 levels were measured using a rapid dipstick test before ERCP, immediately after, and at 1 and 3 hours post-procedure. Serum amylase (AMY) levels were measured 3 hours after ERCP. We evaluated the diagnostic performance (sensitivity, specificity, and accuracy) of UT2 at multiple time points, for the diagnosis of PEP. PEP was defined as an elevation in pancreatic enzyme >3x upper limit of normal with abdominal pain at 24 hours post-pocedure.

Results

A total of 521 patients underwent initial ERCP during the study period, and 337 were included in the final analysis. The median age was 74 years, and 64% were male. A naïve papilla was present in 89% of patients. The indications for ERCP included bile duct stones (39%), malignant biliary obstruction due to pancreatic cancer (13%) or non-pancreatic cancer (18%), benign biliary stricture (5%), diagnostic pancreatogram (24%), and others (1.2%). EST, EPBD, and EPLBD were performed in 37%, 6.5%, and 4.5%, respectively. Prophylactic pancreatic stent placement and rectal NSAIDs administration were performed in 29% and 20%, respectively. PEP occurred in 10% (mild 8.6%, moderate 1.2%, and severe 0.3%) of patients. UT2 demonstrated a trend toward higher sensitivity compared to AMY (AMY: 52.9% vs. UT2 at 0 h: 52.9%, 1 h: 64.7%, 3 h: 64.7%), while AMY exhibited significantly higher specificity (AMY: 92.7% vs. UT2 at 0 h: 65.3%, 1 h: 64.7%, 3 h: 65.0%) and accuracy (AMY: 88.7% vs. UT2 at 0 h: 64.1%, 1 h: 64.7%, 3 h: 65.0%). Notably, 28.5% of patients were positive for UT2 prior to undergoing ERCP. These patients were significantly older (79 vs. 71 years, P < 0.01), more likely to have pancreatic cancer (19.8% vs. 9.5%, P = 0.02), and less likely to have chronic pancreatitis (3.1% vs. 12.9%, P = 0.01). After excluding 96 cases (28.5%) who were UT2-positive before ERCP, we further evaluated the diagnostic performance of UT2 and AMY. UT2 at 0 h had lower sensitivity compared to AMY (AMY: 54.2% vs. UT2 at 0 h: 37.5%, 1 h: 54.2%, 3 h: 54.2%). In contrast, specificity was similarly high across all markers (AMY: 91.7% vs. UT2 at 0 h: 88.9%, 1 h: 87.1%, 3 h: 87.1%). Diagnostic accuracy was comparable between AMY and UT2 (AMY: 88.0% vs. UT2 at 0 h: 83.8%, 1 h: 83.8%, 3 h: 83.8%).

Conclusion

UT2 showed slightly lower predictive performance for PEP compared to AMY. However, excluding UT2-positive pre-ERCP improved the diagnostic accuracy. The diagnostic performance plateaued at 1 hour after ERCP, suggesting its potential utility in predicting PEP earlier.

Disclosure

The author is affiliated with Nipro Corporation through a labor-related arrangement, but has received no financial support or remuneration related to this study.