American Pancreatic Association Practice Guidelines in Chronic Pancreatitis: evidence-based report on diagnostic guidelines

Abstract

The diagnosis of chronic pancreatitis remains challenging in early stages of the disease. This report defines the diagnostic criteria useful in the assessment of patients with suspected and established chronic pancreatitis. All current diagnostic procedures are reviewed, and evidence-based statements are provided about their utility and limitations. Diagnostic criteria for chronic pancreatitis are classified as definitive, probable, or insufficient evidence. A diagnostic (STEP-wise; survey, tomography, endoscopy, and pancreas function testing) algorithm is proposed that proceeds from a noninvasive to a more invasive approach. This algorithm maximizes specificity (low false-positive rate) in subjects with chronic abdominal pain and equivocal imaging changes. Furthermore, a nomenclature is suggested to further characterize patients with established chronic pancreatitis based on TIGAR-O (toxic, idiopathic, genetic, autoimmune, recurrent, and obstructive) etiology, gland morphology (Cambridge criteria), and physiologic state (exocrine, endocrine function) for uniformity across future multicenter research collaborations. This guideline will serve as a baseline manuscript that will be modified as new evidence becomes available and our knowledge of chronic pancreatitis improves.

Fig. 1. Pancreas with chronic pancreatitis (CP)

The stomach is at the top, the duodenum at the lower left, and the spleen on the right with the pancreas extending from the spleen to the duodenum. The pancreas is small, probably because of atrophy. The massively dilated main duct with a white stone is seen in the head and body of the pancreas. These are all characteristics of CP. Photo courtesy of Edward Bradley.

Fig. 2. Pancreas with CP

Note the fibrosis between and surrounding the lobules of acinar tissue. This is perilobular or interlobular fibrosis. The fibrosis extends into the lobule at the center and that is referred to as intralobular fibrosis. There is a chronic inflammatory infiltrate in this pancreas, best seen in the fibrous tissue. Hematoxylin and eosin stain (H&E).

Fig. 3. Perilobular and Intralobular Fibrosis

The collagen is blue. You can see the massive amounts of collagen around the lobule and extending into the lobule. The acini are atrophic. Small ducts along the top margin of the lobule are somewhat dilated. These are all characteristics of CP. There is less inflammatory infiltrate here than in Fig. 2. Connective tissue stain.

Fig. 4. Atrophy and Fibrosis (alcoholic CP)

The amount of collagen (pink) is increased, especially in the left-hand panel, Note the slight dilation of ducts and the loss of acinar tissue. On the right there are 5 islets located close together because of the loss of acinar tissue. Foci of calcification are blue. H&E

Fig. 5. Pancreas in cystic fibrosis

Note the diffuse fibrosis, loss of acinar tissue, persistence of ducts and some islets. The ducts are dilated and contain mucus. This is an advanced stage of cystic fibrosis in which inflammation has largely “burned out”. H&E

Fig. 6. CP can be a patchy or localized process

In the upper left portion of this transected pancreas there is a dilated duct surrounded by scar tissue (fibrous tissue) with virtually complete loss of acinar lobules (WHITE ARROW). In the lower right portion of the same trans-section, there is relatively good preservation of the acinar lobules illustrating that CP can have quite localized involvement(BLACK ARROW).

Fig. 7. Inflammation of pancreatic duct walls is the most distinctive feature of AIP

Although lobules can be involved, inflammation in the duct wall is more conspicuous. On the left there is inflammation in the duct wall (WHITE ARROW) and fibrosis around the duct. On the right there is severe ductitis (YELLOW ARROW) with paraductal and interlobular fibrosis (WHITE ARROW)and atrophy of acinar tissue(BLACK ARROW). H&E

Figure 8. Ultrasound in Chronic Pancreatitis

Transabdominal ultrasound demonstrating calcifications (white arrow) in the pancreas due to chronic pancreatitis.

Figure 9

CT Findings in Chronic Pancreatitis

Figure 10. Ductal changes in Chronic Pancreatitis

Dilated, beaded main pancreatic duct (white arrow) and parenchymal atrophy and calcifications.

Figure 11. Calcifications in Chronic Pancreatitis

Intraductal and parenchymal calcifications (white arrow) in chronic pancreatitis.

Figure 12. CT can appear normal in CP

CT image shows typical pancreatic appearance without calcifications or radiologic evidence to suggest chronic pancreatitis. Follow-up MRI/MRCP showed markedly abnormal main pancreatic duct and side branches.

Figure 13. Duct penetrating sign in “mass-forming” CP

Distinguishing CP from cancer can be difficult in mass forming chronic pancreatitis. Visualization of the pancreas duct as it penetrates the mass (white arrow and circle) on MRI favors a diagnosis of CP. ERCP and biopsy suggested adenocarcinoma but surgical pathology Whipple specimen confirmed chronic pancreatitis.

Figure 14. Classic CP ductal changes

Cambridge 4 (minor main pancreas ductal abnormalities with side branch changes, left) and Cambridge 5 (major main pancreas ductal changes, right) in CP

Figure 15. Glandular atrophy

Sequential (right to left) contrast enhanced MRI showing glandular atrophy and dilation of main pancreas duct in CP

Figure 16. Low T1 Signal

MRI displaying decreased pancreas signal intensity on T1-weighted images (lower right and left). No major CP changes observed on CT (upper left) or MRCP (Upper right)

Figure 17. Delayed Contrast Enhancement

Pre and post contrast MRI showing delayed contrast enhancement of pancreas

Figure 18. Secretin MRCP

Serial sequential images of pancreas displaying ductal and duodenal filling changes after secretin administration

Figure 19. Selected CP EUS criteria

EUS morphologic features of chronic pancreatitis. (adapted from reference 9) A. Hyperechoic foci and strands. B. Lobularity. C. Dilated, irregular pancreatic duct D. Hyperechoic duct margin E. Calcified, shadowing stones.

Figure 20. Figures 20a-3 Cambridge Criteria 1–4

Retrograde pancreatograms exhibiting various stages of change in pancreatic duct for advancing Cambridge criteria 1–4. (adapted from reference 3)

Figure 20. Figures 20a-3 Cambridge Criteria 1–4

Retrograde pancreatograms exhibiting various stages of change in pancreatic duct for advancing Cambridge criteria 1–4. (adapted from reference 3)

Figure 20. Figures 20a-3 Cambridge Criteria 1–4

Retrograde pancreatograms exhibiting various stages of change in pancreatic duct for advancing Cambridge criteria 1–4. (adapted from reference 3)

Figure 20. Figures 20a-3 Cambridge Criteria 1–4

Retrograde pancreatograms exhibiting various stages of change in pancreatic duct for advancing Cambridge criteria 1–4. (adapted from reference 3)

Figure 20. Figures 20a-3 Cambridge Criteria 1–4

Retrograde pancreatograms exhibiting various stages of change in pancreatic duct for advancing Cambridge criteria 1–4. (adapted from reference 3)

Figure 21

Traditional secretin PFT with Dreiling tube

Figure 22

Endoscopic Pancreatic Function Test (ePFT)

Figure 23

New Dreiling Tube

Figure 24

Liguory Drainage Tube (Burton Method)

Figure 25. Correlation of EUS and PFT with Pancreas Fibrosis

There is moderate correlation of EUS and ePFT to pancreatic fibrosis

Figure 26. Diagnostic Accuracy of EUS, ePFT or Combined EUS/ePFT

A combined EUS/ePFT may be the most accurate means of accessing for early chronic pancreatitis

Figure 27. Figure 27a–b. STEP-wise Algorithm Approach to Diagnosis of Chronic Pancreatitis

Step 1: Survey – data review, risk factors, CT imaging. Step 2: Tomography – Pancreas protocol CT Scan, MRI/S-MRCP. Step 3: Endoscopy – EUS (standard criteria). Step 4 – Pancreas function – Dreiling, ePFT. Step 5: ERCP (with intent for therapeutic intervention)

Figure 27. Figure 27a–b. STEP-wise Algorithm Approach to Diagnosis of Chronic Pancreatitis

Step 1: Survey – data review, risk factors, CT imaging. Step 2: Tomography – Pancreas protocol CT Scan, MRI/S-MRCP. Step 3: Endoscopy – EUS (standard criteria). Step 4 – Pancreas function – Dreiling, ePFT. Step 5: ERCP (with intent for therapeutic intervention)