1. Endoscopic Ultrasound in Chronic Pancreatitis
Jon Schneider
March, 2011

2. Origin of EUS
EUS was developed initially for improving imaging of the pancreas
Sivak MV, Kaufman A. Endoscopic ultrasonography in the differential diagnosis of pancreatic disease. A preliminary report. Scand J Gastro, 1986
The close proximity of the pancreas to the gastric and duodenal lumen permits EUS to obtain high resolution imaging without interference by overlying bowel gas
1986 Article: 14 patients

3. Sonographic features of a normal pancreas
The following findings were noted in a study involving 130,951 patients who underwent a screening examination with transabdominal ultrasonography
PD diameter was dilated (>3 mm) in only 0.49 % of individuals (more common in men & in older individuals).
Cystic lesions were detected in 0.21% and calcifications in 0.05% of individuals
--Need to know normal appearance of pancreas so abnormalities can be appreciated
---There was a strong trend toward increasing duct diameter with age
--TUS may underestimate the prevalence of these abnormalities compared with EUS.

4. EUS features of a normal pancreas
3 studies have evaluated the pancreas with EUS in populations of patients without clinical features or obvious risk factors for chronic pancreatitis
homogeneous fine granular appearance with smooth margins
main PD diameter was 2.4 mm in the head, 1.8 mm in the body, and 1.2 mm in the tail
without evidence of side-branch ectasia
more echogenic than liver
A ventral anlage was detected in 45 & 66%
Patient populations:such as those undergoing nonpancreatic tumor staging, evaluation of submucosal tumors or portal hypertension
However, some patients may have had risk factors for chronic pancreatitis (such as heavy ETOH use)
rule….however, control group in 1 study showed uln of the MPD in the head was 3.6mm  rule may lead to overdiagnosis
--If saw side branches, this could be a marker of CP; now with newer echoendoscopes can see it on a regular basis
Ventral anlage: echogenic difference between the ventral and dorsal pancreas

5. Reference Standards
No agreement on an appropriate reference standard for CP
findings on EUS have been correlated with histology, pancreatic function testing, pancreatography
particularly problematic with early or minimal change CP
--Autopsy studies on the elderly with no history of pancreatic disease revealed fibrosis and atrophy

6. Comparison of EUS findings with histopathology in chronic pancreatitis
34 patients who underwent EUS followed by pancreatectomy or open surgical biopsy
21 for CP, 12 for pancreatic cancer
Overall, 68% were considered to have CP based upon the histologic findings
Total # of EUS criteria present were predictive of histologic CP
Sensitivity & specificity using a threshold diagnosis for:
≥3 criteria were 87% and 64%
≥4 criteria were 78% and 73%
≥5 criteria were 60% and 83%
≥6 criteria were 43% and 91%
--The authors concluded that a minimum of four or more criteria was optimal.
--Biopsy isn’t perfect because CP is a patchy disease so it’s possible to miss; no standard definition regarding amount of fibrosis or atrophy needed to make the diagnosis of CP
Zimmerman, MJ, Mishra, G. GIE 1997

7. From UAB, 42 patients
--2nd table: Sensitivity, specificity for individual EUS features for CP

8. Secretin PFT, EUS, ERP performed EUS + if >2 criteria seen
Aim of study was to compare ERP and EUS for the prediction of exocrine insufficiency as detected by a secretin endoscopic PFT
Secretin PFT, EUS, ERP performed
EUS + if >2 criteria seen
ERCP + if Cambridge Class II or worse
>3 abnl side-branches, normal or minimally dilated PD
-Cleveland Clinic
-Patients with chronic abd. Pain undergoing evaluation for presence of CP; total of 83
-ERCP is a sensitive test to evaluate ductal changes however drawbacks would include no evaluation of the parenchyma, risk of pancreatitis…duct changes can be normal finding in elderly as well as those who drink alcohol but don’t have clinical evidence of pancreatitis
-pancreatic FT is used as a reference standard as it detects mild exocrine insufficiency as a surrogate for fibrosis (drawback is often normal in early stages of CP)—duod. Aspirate over 60 minutes after IV secretin, peak bicarb administration <80 was diagnostic

9. ERP findings of CP A: CC 0 (normal): normal main duct, no
abnormal side-branches
B: CC II (mild): minimally dilated MPD with numerous abnormal
side-branches
C CC III (moderate):
dilated MPD &
numerous abnormal side-branches,
D CC IV (severe):
Dilated MPD with stones or strictures

10. Given less risk with EUS, safer test for diagnosis of CP
EUS & ERP demonstrate good agreement and are equally diagnostic in the presence of both mild and severe structural changes
Given less risk with EUS, safer test for diagnosis of CP
Kappa 0.69

11. Bradley Shepherd, MD
Purpose was to establish a consensus-based criteria for EUS features of CP
32 internationally recognized endosonographers anonymously voted on terminology of EUS features, rank order, and category (major vs minor criteria)
Consensus was defined as greater than two thirds agreement among participants
--Rosemont, IL; in 2007, group of experts from US and Japan
--Wanted to divide criterion into major and minor based on their relative positive predictive value for CP

12. --EUS scanning for CP in the pancreatic head were not recommend, because the ventral pancreas is normally more hypoechoic than the dorsal gland and, therefore, may falsely show pancreatic abnormalities

13. --Results of the deliberations do not provide validation for the recommendations
--Feel that these guidelines represent an improvement over the previous means of EUS diagnosis, which assigned equal importance to each criterion

14. May ask “why not just take a biopsy while doing the EUS
May ask “why not just take a biopsy while doing the EUS?”—low accuracy, risky

15. CP-Lobularity, hyperechoic stranding, irregular PD
Normal

16. Mild: lobularity, hyperechoic foci and strands, duct irregularity
Normal
Severe: hyperechoic foci & strands, parenchymal calcifications, cystic change, lobularity
Severe: ductal dilation and intraductal calcification
A Normal pancreatic duct and parenchyma.
B Mild EUS changes (four criteria: lobularity, hyperechoic foci and strands, duct irregularity).
C Severe EUS parenchymal changes (hyperechoic foci and strands, parenchymal calcifications, cystic change, lobularity).
D Severe ductal EUS changes (ductal dilation and intraductal calcification)

17. Calcification within the wall of the dilated MPD
Parenchymal echogenic foci are present

18. Honeycomb appearance
Lobularity

19. Dilated pancreatic duct (7 mm) with MPD calculi with shadowing

20. Dilated PD with marked contour irregularity

21. Dilated PD with side-branch ectasia

22. PD with hyperechoic borders

23. Interobserver Reliability Wiersema, Endoscopy, 1993
varies depending upon the specific finding
agreement was:
88 % for hyperechoic foci
94 % for focal reduced echogenicity
94 % for lobularity
83 % for hyperechoic duct margins
94 % for duct irregularity
Linear versus Radial EUS Stevens, Endoscopy, 2009
noninferiority study of 100 patients
no significant difference between linear EUS and radial EUS with regard to sensitivity, specificity, accuracy

24. Distinguishing chronic pancreatitis from pancreatic cancer
EUS-FNA of the pancreas is challenging in patients with CP
EUS alone cannot reliably differentiate malignant from inflammatory lesions
Cytologic evaluation of pancreatic tissue in the setting of chronic inflammation is very difficult
-Because focal pancreatitis and adenocarcinoma have similar EUS appearance
-The inflammatory infiltrate may obscure or simulate a pancreatic malignancy
--Compounded by the facts that patients with chronic pancreatitis are at increased risk of developing pancreatic ductal adenocarcinoma and patients with pancreatic ductal adenocarcinoma often have focal areas of chronic pancreatitis

25. 282 consecutive patients who underwent a total of 300 EUS-FNA
The diagnostic yield and accuracy of EUS-FNA was compared between patients with and without CP
CP defined as >4 criteria
--Because of the lowered sensitivity of EUS-FNA in CP, recommend surgery to patients if clinical suspicion for cancer remains high
--One thought is that in severe CP, calcifications cause acoustic shadowing that may conceal a malignant mass
--Increased number of needle passes, repeating the EUS-FNA, and using on-site cytology interpretation can certainly overcome the issue of inadequate yield

26. Conclusion
The EUS diagnosis of CP relies on quantitative and qualitative parenchymal and ductal criteria
Generally accepted that in the absence of any criteria, CP is unlikely
If ≥5 criteria are present, CP is likely
Despite ERCP findings
The clinical significance of fewer (1 to 4) features found on EUS is unclear
1 problem is can see these changes normally in elderly: One practice is to raise the threshold of diagnosis to a higher # of criteria in the elderly
Another problem is that EUS is operator dependent and diagnosis is based on subjective criteria