ERCP: A Potential Cause and a Potential Cure of Pancreatitis

1. ERCP: A Potential Cause and a Potential Cure of Pancreatitis Grace H. Elta, MDProfessor of MedicineDivision of GastroenterologyUniversity of Michigan

2. Complications of ERCP General Considerations: • Is the indication for ERCP strong enough to warrant the risks? • Low suspicion: Alternative imaging • Death in 0.4 -0.6% • Does the performing physician have adequate case volume?

3. *P <0.05 * Overall Severe * 2.3 0.9 * Case Volume of Endoscopist

4. ERCP Complications • Pancreatitis: 6.7%* • Perforation: 0.3% • Cholangitis: <1% • Cardiopulmonary / sedation: <1% • Failed procedure *Freeman ML et al GIE 2001

5. Causes of Post-ERCP Pain • Pancreatitis • Transient Pain • Cholangitis • Perforation

6. Post-ERCP Pain: What does it mean? • Pain at 2 hrs post-ERCP*: • 2/3 of pts developed pancreatitis • 1/3 of pts who did not get pancreatitis • Recovery room pain not very specific • 33% of panc. presents >4hrs post-ERCP** • Admission required in 12% with >1 risk factor and 4% without any *Gottlieb GIE 1996 **Freeman NEJM 1996

7. Post-ERCP Pancreatitis • Definition requires all 3: • New or worsened pain • amylase 3X ULN > 24 hrs post-ERCP • requiring >2 days hospitalization • Severity: • Mild: <4 days hospitalization • Moderate: 4-10 d. hospitalization • Severe: >10 d. hospitalization

8. Risk Factors for Post-ERCP Pancreatitis

9. Risk Factors for Post-ERCP Pancreatitis

10. Risks for Pancreatitis: Prospective US Multi-Center Study* Multivariate risk factorsOdds Ratio Minor sphincterotomy 3.8 Suspected SOD 2.6 Prior ERCP-pancreatitis 2.0 Age <60 1.6 2 or more pancreatic injections 1.5 Trainee involvement 1.5 Not risk factors: female gender, idiopathic pancreatitis, difficult cannulation, major sphincterotomy, SOM *Cheng AJG 2006

11. Does SOM Increase Procedure-Induced Pancreatitis? • Suspected SOD pts: • ERCP with SOM vs. ERCP alone—No differences in pancreatitis rates (26%)* • Compared to 3% rate in bile duct stone pts • Pancreatitis risk increased by ES and pancreatography Conclusion: It’s the diagnosis (suspected SOD) not the manometry that increases risk *Singh GIE 2004

12. Medications to Lower Post-ERCP Pancreatitis *4 positive / 1 negative studies **Single positive study

13. NSAID Meta-analysis • 4 RCTs: 879 patients* • Diclofenac / indomethacin vs. placebo • Relative risk of pancreatitis: 0.35 • 65% decrease in pancreatitis, 90% decrease in severe pancreatitis • NNT to prevent one episode: 15 *Elmunzer Gut 2008

14. Techniques to Lower Post-ERCP Pancreatitis • Wire cannulation instead of contrast* • Temporary PD stenting • Not clearly shown to be helpful: • Post-biliary ES botox • Pure cut cautery may be safer than blended cut • Low osmolality contrast * Lella GIE 2004

15. Temporary Pancreatic Stenting • RCT: Stent lowers risk in biliary SOD pts* • Used for other high risk cases • Single pigtail flangeless 3F stents appear safer and more effective** • Spontaneous stent passage: 70-85% • Successful placement in 4 studies=88% *Tarnarsky Gastroenterology 1998 ** Rashdan Clin Gastro & Hep 2004

16. Stenting to Minimize PancreatitisMeta-Analysis Singh P. GIE 2004;60:544.

17. Problems with Prophylactic PD Stent • Technical difficulty in placement • Small stents require 0.018 guide wire • Increased risk in failed stent placement • May require repeat endoscopy • Increased cost • Possible stent-induced damage • Lack of expert agreement on methods

18. Survey on PD Stents: Who should get one? Which one? • Agreed upon indications: • SOD • Pancreatic sphincterotomy (minor & major) • Ampullectomy • Indications according to some: • Pre-cut sphincterotomy (71%) • Prior post-ERCP pancreatitis (64%) • Suspected SOD / normal or no manometry (60%) • Traumatic or difficult cannulation (44%) • No agreement on stent size and length, how long stents left, and retrieval methods *Brackbill GIE 2006

19. Post-ERCP Pancreatitis: Conclusions • Most common complication, 1/3 pts. take > 4hrs to present • Patient-related and technique-related risk factors are major determinants of risk • Limit pancreatic injection / wire for cannulation • Temporary PD stenting for high risk pts

20. Endotherapy for the Pancreas • Indications: • Acute idiopathic pancreatitis • Chronic pancreatitis pain

21. Idiopathic Acute Pancreatitis:Possible Etiologies • Microlithiasis / missed stones in GB / ducts • Pancreas divisum • Sphincter of Oddi dysfunction • Neoplasms • Subtle chronic pancreatitis • Autoimmune / genetic pancreatitis • Missed diagnosis of hypertriglyceridemia or hypercalcemia

22. Idiopathic Pancreatitis:Possible Additional Labs • Cystic fibrosis genotype • Positive in 20% (range: 4-37%) • CA19-9 in suspected cancer • ANA and IGG4 subtype • Ionized serum calcium / parathormone • FH: trypsinogen gene and Spink1 • Repeat non-fasting triglyceride

23. Idiopathic Pancreatitis: Diagnostic Choices • Diagnostic Choices • Wait for second episode • EUS • MRCP +/- secretin stimulation • ERCP with manometry • Empiric cholecystectomy • Factors affecting choice • Age= >40 years: 21% had neoplasm* • Absent gallbladder *Choudhari AJG 1998

24. What is the role of Microlithiasis? • Microlithiasis: small (1-2 mm) stones • Sludge: Collection of crystals, mucin, glycoproteins, and cellular debris • Sludge may contain microlithiasis: terms used interchangeably clinically

25. Microlithiasis in IAP: Gallbladder in Situ • High incidence (60-80%) centers of IAP due to microlithiasis • Low incidence (6-8%) centers Evaluation/Rx options: • Empiric cholecystectomy / trial of Urso • Bile crystal analysis: sensitivity 66% • EUS: Superior to crystal analysis* *Dahan Gut 1996

26. Does Microlithiasis cause IAP Post Cholecystectomy? • Bile crystals rare in biliary SOD* • No biliary crystals in IAP pts** Conclusion: Bile duct Stones / microlithiasis are very rare cause of IAP post-cholecystectomy, best diagnosed by EUS*** *Quallich GIE 2001 **Law GIE 2002 ***Scheiman AJG 2001

27. Acute Idiopathic Pancreatitis Diagnostic Tests • EUS • Accurate for P. divisum, tumors, bile duct or gallbladder stones • Pro: Safe Con: Not therapeutic, miss SOD • MRCP • Accurate for P. divisum, variable accuracy for tumors and missed stones, miss SOD • + Secretin: Improve image quality but value of P. duct dilation / flow is controversial

28. Diagnostic Yield of EUS in IAP *Yusoff GIE 2004

29. Chronic Pancreatitis Presenting as IAP • “Small duct” or minimal change • Difficult diagnosis • EUS: need > 5 criteria for certainty • Panc func tests: Also has accuracy issues • Treatment options: • Medical therapy first • ? Value to endoscopic therapy • Surgery relegated to resection

30. EUS Diagnostic Accuracy in Chronic Pancreatitis • Number of EUS criteria only weakly correlated with fibrosis score* • >3 criteria: 80% sensitive & specific • EUS true cut and FNA also have poor specificity (65%) • Only moderate interobserver agreement on individual criteria** *Chong GIE 2007 **Wallace GIE 2001

31. EUS in IAP Patient

32. Endotherapy for P. Divisum

33. Pancreas Divisum Treatment • Pancreas divisum as cause of IRP • Rx outcome: 127 pts in 8 series81% no further episodes in mean f/u of 27 mo • Long term (61 mos) f/u of 28 IRP pts* • 23 cured, 5 better, 3 repeated ERCP • NK vs traction sphincterotome?** • Restenosis rate: 13% NK vs 25% TS *Alsolaiman T1528 GIE 04 **Berkes T1532 GIE 04

34. Acute pancreatitis can be a neoplastic presentation • Ampullary neoplasm • Ductal cancer / isolated MPD stricture • IPMN • Islet cell / metastatic cancer

35. Ampullary Neoplasm

36. Pancreatic Duct Stricture

37. EUS of Case: Early Pancreatic Cancer

38. Intraductal Papillary Mucinous Neoplasm: IPMN

39. SO Anatomy

40. Does SOD cause Idiopathic Acute Pancreatitis? Pro: • Present in 30-60% of IAP pts • Pts with panc. SOD more likely to get post-ERCP pancreatitis than those with normal SOM (26% vs. 7%)* • 60-80% IAP pts improve after sphincter ablation *Tarnasky Gastroenterology 1998

41. Does SOD cause Idiopathic Acute Pancreatitis? Pro: • Present in 30-60% of IAP pts • Pts with panc. SOD more likely to get post-ERCP pancreatitis than those with normal SOM (26% vs. 7%)* • 60-80% IAP pts improve after sphincter ablation *Tarnasky Gastroenterology 1998

42. Contemporary* Classification for Suspected Pancreatic SOD Type I -Pancreatic type pain -Amylase/lipase elevation -Dilated Pancreatic duct Type II -Pancreatic type pain -Either abnormal pancreas enzymes or duct dilation Type III -Pancreatic type pain only *Classic System includes delayed drainage >8 min

43. Why Pancreatic SOD Classification is Not Useful • Few Type I pts reported, most IAP pts have normal PD caliber • IAP pts fit into Type II category and are primary pts of interest • Type III—an uncertain diagnosis

44. Pancreatic SOD Therapy ChoicesWhat Type of Sphincterotomy? • Biliary ES: • Proposed as safer 1st step* • Dual purpose: treats microlithiasis and lowers panc SO pressure somewhat • Efficacy is only 28-50% • Higher failure rate than panc or dual ES *Levy AJG 2001

45. Pancreatic SOD Therapy ChoicesWhat Type of Sphincterotomy? • Pancreatic ES alone • Treats correct portion of SO • Creates small biliary ES • Complete dual ES • Surgical sphincteroplasty • Insufficient data to support clear superiority for any method

46. 65 yo woman, 3 episodes of IARP in one year

47. Algorithm for IARP Idiopathic Acute Pancreatitis ↓ R/0 autoimmune / genetic pancreatitis ↓ EUS → diagnosis/treatment ↓ no diagnosis ERCP with manometry for >1 attack

48. Pancreatic Endotherapy for Chronic Pancreatitis • Duct disruptions, pancreatic ascites • Pseudocyst drainage • Per ampulla-communicating cysts • Transluminal stents • Treatment of chronic pain • Stone clearance • Stricture treatment

49. Stent for Duct Disruption • Resolution: 60-80% • Bridge disruption • Less success in AP

50. Rules for Endoscopy of Pancreatic Pseudocysts • Symptomatic • True PP-not acute fluid collections (<4 wks) • EUS to assess wall (<10 mm) & R/O vessels • Antibiotic coverage • Surgical back-up