Endoscopic Ultrasound (EUS), Chronic Pancreatitis, and Pancreatic Cancer (PC) Precursors in High Risk Individuals

EUS and ERCP in high risk individuals (HRI) with an inherited predisposition for PC have shown chronic pancreatitis (CP)-like abnormalities but the significance of these changes has not been understood. AIM: To determine the prevalence of pancreatic EUS abnormalities in asymptomatic HRI and correlate these with ERCP, pancreatic function, and pathology. Methods: In 2 prospective cohort studies (1998–2004), 112 HRI (105 HRI with ≥2 affected first degree relatives with PC, 7 had Peutz-Jeghers syndrome) had screening EUS. ERCP was performed by another endoscopist without knowledge of EUS findings. Serum trypsin and secretin stimulated-peak bicarbonate concentration was measured in HRI and normal controls. Surgery was performed for suspected neoplasms or dysplastic tissue in EUS-FNA. Pancreata were examined by an experienced pathologist. Results: The prevalence of EUS changes of CP (≥4 of 9 features) in HRI was 72.3%. Mild ERCP abnormalities were present in 85.6%. Serum trypsin was lower in HRI than in controls (mean=66.4 vs. 169.1, p=.0001). But, mean peak bicarbonate concentration was similar in HRI and controls (106.8 meq/L vs. 105.4 meq/L, respectively, p=0.83). Subtotal pancreatectomy was performed on 15 HRI: pancreatic neoplasms were found in 11 and pancreatic intraepithelial neoplasia (PanIN) 1–3 were present in 13. The mean PanIN density in HRI pancreata was 12.2% (range 1–27.3%). Both IPMNs and PanIN were associated with parenchymal lobulocentric atrophy and CP. PanIN density was positively and linearly correlated with the number of EUS features of CP (Spearman's R=0.87, p=.005) but not ERCP grade of CP (Spearman's R=0.41, p=.31). Conclusions: EUS features of CP are highly prevalent in HRI with an inherited predisposition to PC and are associated with both IPMN and PanI. EUS features of CP correlate with PanIN density and PanIN-associated lobulocentric atrophy.