Diagnostic Testing

Clinical presentation, radiologic imaging, and pancreatic function testing (PFT) are pillars of investigation for the diagnosis of CP, which is a complex illness that often eludes diagnostic certainty. Radiologic modalities are helpful for visualizing the pancreas and associated calcifications, which is a common radiologic finding in CP. Imaging is often the first step in diagnostic testing. Noninvasive modalities include computed tomography (CT) and magnetic resonance cholangiopancreatography (MRCP). More invasive tools, such as endoscopic retrograde cholangiopancreatography (ERCP) and endoscopic ultrasound (EUS), are helpful in the evaluation of more challenging cases.3 

Computed Tomography

Diagnostic testing often begins with abdominal CT with pancreatic protocol. CT images are effective for detecting scattered pancreatic calcifications, which is suggestive of late-stage CP. CT is also useful in assessing for disease complications, such as pseudocysts and necrosis, and for differentiating similar diagnoses such as pancreatic adenocarcinoma, cholangiocarcinoma, and other biliary tract pathology. Lack of sensitivity in earlier stages of CP, however, limits the capability of CT to visualize ductal and parenchymal derangements.3

Magnetic Resonance Imaging

MRI is additive in diagnosing CP. According to the American Pancreatic Association, MRI is more sensitive than CT in the evaluation of CP in earlier stages, conferring an important advantage for early clinical intervention and enhanced disease outcomes. Although several MRI protocols are available, the MRCP/secretin protocol is regarded as the most accurate.3 MRCP involves an MRI of the abdomen focused on structural images of the pancreas, bile duct, and gallbladder. This method provides more definitive visualization than MRI of the abdomen alone.3 The MRCP/secretin protocol involves intravenous administration of secretin, a hormone that stimulates pancreatic exocrine secretion. Images are generated during secretin administration to qualify pancreatic function while also visualizing pancreatic structure. Furthermore, secretin administration increases the sensitivity and specificity of MRCP.3

Endoscopic Ultrasound

EUS is regarded as the most sensitive imaging tool for the diagnosis of CP and identification of ductal and parenchymal abnormalities early in the disease.8 EUS provides a high sensitivity of 91% depending on which diagnostic criteria are employed, conventional or Rosemont.5,8 The limitation of EUS, however, is low specificity. Yet as with sensitivity, specificity relies on the set of criteria employed.5,8 Conventional criteria are more sensitive, whereas Rosemont criteria are more specific.8 Regardless of the criteria used, EUS remains a useful test. Diagnosis should be established based on signs and symptoms consistent with CP in combination with EUS or other imaging modality.5

Pancreatic Function Testing

PFT is useful in diagnosing CP based on quantification of exocrine insufficiency.3 Methodology of PFT may involve either direct or indirect approaches. Direct PFT involves administration of secretin followed by endoscopic collection of stimulated pancreatic secretions while obtaining simultaneous EUS imaging. Direct PFT is distinct from the MRCP/secretin protocol in that it provides quantitative physiologic assessment. In contrast, MRCP/secretin testing is a qualitative evaluation of exocrine insufficiency wherein no fluid is collected or measured. Since direct PFT is invasive, it is rarely employed today. Indirect PFT is far more commonly performed and involves the assessment of fecal elastase 1 or fecal fat concentrations in a stool specimen. Fecal elastase 1 is a pancreatic enzyme that digests protein and aids in transport of cholesterol.3 Fecal elastase 1 concentrations <200 μg/g of stool are abnormal and indicative of some degree of exocrine insufficiency. Fecal elastase 1 concentrations <100 μg/g of stool indicate severe exocrine insufficiency and are supportive of a diagnosis of CP. Moreover, this assessment requires only 1 stool sample and is not affected by pancreatic enzyme replacement therapy (PERT).3,5,9  Fecal fat measurements are less specific but still may be considered. Detection of ≥7 g of fat per 24 hours during a 72-hour collection period is abnormal and suggestive of a diagnosis of CP.3,5,9 When interpreting indirect PFTs, confounding elements  such as diarrhea and bacterial overgrowth can cause false positives. Likewise, the presence of acute pancreatitis can cause false negatives. Celiac disease and inflammatory bowel disease must be considered in the interpretation of PFTs.3

Endoscopic Retrograde Cholangiopancreatography

ERCP is intended primarily for therapeutic purposes and is rarely used for diagnosis of CP. When selected for diagnosis, ERCP allows for performance of diagnostic biopsies. ERCP is invasive and carries significant risk for triggering acute pancreatitis. Additional limitations include visualization restricted to the ductal system, intraoperator bias, and lack of specificity.3 Histology obtained by ERCP lacks sensitivity and specificity due to sampling error.5