Endoscopic Ultrasound in Chronic Pancreatitis Jon Schneider March, 2011

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

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.

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) --3-2-1 rule….however, control group in 1 study showed uln of the MPD in the head was 3.6mm  3-2-1 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

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

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

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

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

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

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

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

--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

--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

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

CP-Lobularity, hyperechoic stranding, irregular PD Normal

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)

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

Honeycomb appearance Lobularity

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

Dilated PD with marked contour irregularity

Dilated PD with side-branch ectasia

PD with hyperechoic borders

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

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

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

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