1. Role of EUS in pancreato- biliary Disorders A Aljebreen M.D, FRCPC Gastroenterology Division, KKUH, King Saud University EUS meeting, KFMC, Dec 16, 2006

2. Objectives Role of EUS in Role of EUS in Pancreatic cancers Pancreatic cancers Pancreatic neuroendocrine tumors Pancreatic neuroendocrine tumors Pancreatic cystic lesions Pancreatic cystic lesions Pancreatitis Pancreatitis Choledocholithiasis Choledocholithiasis Periampullary tumors Periampullary tumors

3. Pancreatic cancers

4. Backgrounds Data indicate that incomplete resection and positive nodes may convey poor long-term survival, equivalent to vascular encasement. In addition, the increasing use of complementary endoscopic techniques, including duodenal endoprosthetic placement, biliary decompression via ERCP, and EUS placement of celiac neurolysis, obviates the necessity for reliance on surgical techniques for the palliation of obviously unresectable or incurable malignancies.

5. Resectability of PC: Backgrounds An apparent clean surgical resection is needed for potential cure. During staging, 50% have mets and 30-35% have locally advanced unresectable tumors 15-20% of tumors are resectable. Surgical resection is curative in a small percentage of patients (15-20% 5-year survival rate of those resected). Niederhuber et al. Cancer 1995; 76: 1671-7.

6. EUS diagnostic accuracy Staging sensitivity with EUS has consistently been reported to be over 90%. EUS is also more accurate in the assessment of vascular invasion that might preclude surgical resection (compared to h-CT/MRI) Rösch et al. Gastrointest Endosc Clin N Am 1995;5:735-9. Yasuda et al. Endoscopy 1993;25: 151-5. Palazzo et al. Endoscopy 1993;25:143-50. Brugge et al. GI Endosc 1996;43:561-7.

7. Mertz et al. GI Endoscopy 2000 35 patients, retrospective

8. Gress et al. GI Endoscopy 1999

9. Radiologist DATA? Data from 30 pts with suspected pancreatic ca a 92% sensitivity & 93% overall accuracy for h-CT a 100% sensitivity & 93% overall accuracy for EUS. The accuracy in predicting the tumor resectability was 90% for both techniques Accuracy for predicting unresectability was 100% for helical CT and 86% for EUS (over staging). Legmann et al. AJR 1998

10. h-CT? Fine section h-CT: 90% sensitive, 90% sensitivity for liver mets, 80-90% sensitive for vascular invasion Fine section h-CT: 90% sensitive, 90% sensitivity for liver mets, 80-90% sensitive for vascular invasion Specificity of HCT for assessment of resectability due to vascular invasion is close to 100% Specificity of HCT for assessment of resectability due to vascular invasion is close to 100% MRI has almost the same sen and sp rates. MRI has almost the same sen and sp rates.

11. What are the remaining indications for EUS in pancreatic ca? 1. 10% of PC (20-30% of PC<2cm) are not demonstrated by h-CT Sensitivity of EUS is close to 100% Sensitivity of EUS is close to 100% 2. Demonstration of N2-positive nodes (celiac, mesentric),+ EUS FNA for confirmation. 3. 3. EUS is the most effective method for biopsy of solid pancreatic masses whatever the size is or the location.

18. FNA for solid pancreatic mass All areas of pancreas including uncinate process and tail, diameter >5mm Low complication rate ~ 1-2% (pancreatitis, haemorrhage) ? Risk of peritoneal seeding NPVPPVspecificitySensitivity 25-85%100%95-100%75-93% Vilmann, Wiresma, Giovannini, Chang, Gress, Bhutani, Hawes, Williams, Palazzo

20. Mallery et al. GI Endoscopy 2002

21. Suspected pancreatic mass Ultrasound H-CT No Mass Mass EUS +/- FNA Bx (CT, EUS or ERCP) Palliation (biliary stent/CPN, oncology) ERCP/Stent Surgery Cholangitis OR delayed resection + jaundice/pruritu s Unresectable Resectable Unresectable Resectabl e Unresectable

23. EUS- guided Plexus Block/Neurolysis (CPN)

24. Technique

25. Complications Mild complications include transient diarrhea (4%-15%), transient orthostasis (1%), transient increase in pain (9%). Major complications (2.5%) retroperitoneal bleeding peripancreatic abscess. The patients typically receive IV 0.9% saline during the procedure. They should be monitored for orthostasis for 2 hours after the procedure.

26. EUS- guided CPN: Results Wiersema's initial study of EUS-CPN in patients with pancreatic cancer showed a significant reduction in pain that persisted for 20 weeks (2 weeks for chronic pancreatitis). It reduced pain scores in 78% of patients which is similar to that achieved by surgical and transcutaneous reports (Gunaratnam et al GI Endosc 2001) Ischia et al. found CPN to be more effective when applied soon after the diagnosis rather than late in the course.

28. Neuroendocrine Pancreatic Tumors Up to 30 % of patients with gastrinomas or insulinomas who undergo surgery fails to have localization of the tumor during surgery Up to 30 % of patients with gastrinomas or insulinomas who undergo surgery fails to have localization of the tumor during surgery Rosch Gastroenterology 92 Rosch Gastroenterology 92 A series of 37 patients who had had non-diagnostic CT and US proceeded to have pre-op EUS. A series of 37 patients who had had non-diagnostic CT and US proceeded to have pre-op EUS. 22 underwent selective angio. 22 underwent selective angio. EUS had sensitivity of 82% compared with 27% for angio and the specificity of EUS was ~95%. EUS had sensitivity of 82% compared with 27% for angio and the specificity of EUS was ~95%. Rosch et al, NEJM 92 Rosch et al, NEJM 92

31. Pancreatic Cystic neoplasms

32. DDX Pseudocysts (~90% of PCL) Benign: *Serous cystadenoma. *Others Malignant potential: Mucinous cystadenoma (commonest after pseudocysts) Intraductal papillary mucinous tumor (IPMT). Others Malignant: Cystadenoca Necrotic adenoca

36. EUS and PCL EUS imaging findings are not sufficient to reliably distinguish between benign and those e malignant potential. The main use of EUS is to guide aspiration of cystic lesion to obtain fluid for cytologic and biochem analysis. Is it important to differentiate?

40. EUS aloneCytologyCEA>3.1 ng/mL* CA 19-9 >37 U/mL* Sensitivity (95% CI) 50% (16-84%)71% (44-90%)78% (40-97%)82% (48-97%) Specificity (95% CI) 56% (30-80%)96% (78-99%)82% (48-97%)90% (56-98%) NPV (95% CI)69% (39-91%)82% (62-94%)79% (49-95%)75% (43-95%) PPV (95% CI)36% (11-69%)92% (64- 99.8%) 78% (40-97%)90% (56-99.8%) Accuracy (95% CI) 54% (34-74%)85% (74-96%)78% (61-95%)82% (66-98%) Aljebreen et al (in press) 41 prospective patients Aim: diagnostic accuracy of EUS/CEA, CA 19-9 & cytology to differentiate benign from malignant/pre- malignant pancreatic cystic lesions

41. FNA complications There is a risk of infecting cyst fluid, so ABX prophylaxis is advisable. There is a risk of infecting cyst fluid, so ABX prophylaxis is advisable. There is also 1% risk of causing acute panc especially for pancreatic head lesions. There is also 1% risk of causing acute panc especially for pancreatic head lesions. Bleeding is an uncommon complication. Bleeding is an uncommon complication.

42. 337 patients with cystic lesions underwent prospective EUS and FNA. 116 (mean age 63) underwent surgical resection of the cystic lesion and the histology was used to determine the type of the cyst. EUS morphology was prospectively collected (microcystic= benign, macrocystic= mucinous, mass=malignant, unilocular=pseudocyst). W Bruggie, Gastroenterology, 2004

43. Results CEA provided the greatest accuracy for mucinous and malignant. CEA provided the greatest accuracy for mucinous and malignant. The optimal diagnostic cut-off for CEA was 158 pg/ml (mucinous) and 1872 pg/ml (malignant). The optimal diagnostic cut-off for CEA was 158 pg/ml (mucinous) and 1872 pg/ml (malignant). CEA negatively correlated with predicting serous cystadenoma. CEA negatively correlated with predicting serous cystadenoma.

44. Results The findings of a microcystic morphology was nearly diagnostic of a serous cystadenoma. Malignant cytology was highly specific but insensitive (17%). The use of all 3 tests provided the greatest diagnostic accuracy for all types of cyst.

45. Choledocholithiasis In prospective studies, EUS has demonstrated a sensitivity of >95% for the detection of choledocholithiasis. These results compare favorably to ERCP and are superior to conventional ultrasound and clinical history without the inherent risk of post-procedural pancreatitis. EUS has also been shown to be a cost-effective initial screening study, in lieu of ERCP for patients with a low or intermediate risk of bile duct stones.49 EUS does not have the therapeutic capacity of ERCP and cannot help in stone removal. The precise clinical role of EUS remains to be defined. Canto et al. GI Endosc 1998;47:439-48.

48. Biliary cancers Cancers of the biliary tract (gall bladder adenocarcinoma and cholangiocarcinoma) have also been staged by EUS with improved staging accuracy compared to other imaging techniques, although the data are considerably limited as compared to pancreatic malignancy.

49. Tierney et al, GI endoscopy 2001

50. Cannon et al, GI endoscopy 1999

52. Conclusion EUS has a major role in not only in diagnosing and staging pancreatic tumor but also as a therapeutic toll for patients with pancreatic tu pain. EUS has a major role in not only in diagnosing and staging pancreatic tumor but also as a therapeutic toll for patients with pancreatic tu pain. EUS has the best diagnostic accuracy in patients with small pancreatic lesions especially neuroendocrine tumors EUS has the best diagnostic accuracy in patients with small pancreatic lesions especially neuroendocrine tumors EUS is the gold standard in diagnosing pts with chronic pancreatitis. EUS is the gold standard in diagnosing pts with chronic pancreatitis.