Controversies in Gallstone Pancreatitis: An Evidence-Based Approach

1. Controversies in Gallstone Pancreatitis: An Evidence-Based Approach TM Mastracci and MJ Marcaccio Department of Surgery McMaster University

2. �RomancingtheStone�

3. Addressing the Controversy� in Six Simple Questions!

4. Mastracci/Marcaccio 2005 Introduction The literature is difficult to interpret because of large series with heterogeneous populations Our purpose is to examine the evidence to address specific clinical scenarios that are commonly encountered in General Surgical practice.

5. Mastracci/Marcaccio 2005 Our Questions What is the incidence of finding CBD stones in gallstone pancreatitis? Can we alter the course of an episode gallstone pancreatitis by treating a CBD stone? In a mild course of GSP which has settled, do we need to worry about potential common duct stones at the time of LC? In resolving, uncomplicated pancreatitis, what is the appropriate management of potential CBD stones? What is the best timing for LC as definitive treatment after an episode of GSP? What is the relative value of ES or LC as definitive treatment to prevent recurrent acute pancreatitis?

6. What is the incidence of finding common bile duct stones in gallstone pancreatitis?

7. Mastracci/Marcaccio 2005 Gallstone Pancreatitis: The Risk The presence of gallstones increases the risk of pancreatitis to levels 15 to 20 times the average population <Moreau et al>

8. Mastracci/Marcaccio 2005 Gallstone Pancreatitis Bernard 1852 First report questioning an association between gallstones and pancreatitis Prince 1882 Boston Medical/Surgical Journal (vol 107) First publication suggesting a link between stones and pancreatitis Opie 1901: Mechanism for gallstone pancreatitis: impaction of a gallstone at the ampulla Post-mortem dissection of bile ducts in pancreatitis patients

9. Mastracci/Marcaccio 2005 Gallstone Pancreatitis Acosta 1974 Linked the passage of gallstones through the CBD to pancreatitis Screening the stool Found gallstones in 94% within the first 10 days of presentation

10. Mastracci/Marcaccio 2005 Gallstone Pancreatitis Kelly 1976 Presence of gallstones in the stool of patients with gallstone pancreatitis was significantly more common than in those patients with other forms of biliary symptoms. Stones tended to appear in stool specimens as symptoms improved, suggesting that passage of the stone correlates with clinical improvement

11. Mastracci/Marcaccio 2005 Incidence of CBD Stones Kelly 1974, 1982 Ampullary calculi in 5 � 8% of patients with pancreatitis at the time of surgery CBD stones were present in 55% of patients undergoing early surgery 18% of those whose surgery was delayed Oslo 1985 Annals of Surgery 457 pts undergoing OC + history of pancreatitis, incidence of CBD stones = 8/457

12. Mastracci/Marcaccio 2005 Incidence of CBD Stones Folsch 1997 ERCP-based Study 238 Patients with acute pancreatitis 126 ERCP within 72 hours ? 58 had Stone in CBD 112 Patients ? ERCP within next 3 weeks (with high risk criteria) ? 22 Patients had ERCP, 13 had CBD Stones Uhl 1999 Surgical Endoscopy 77 Patients with gallstone pancreatitis 65 ERCP within 14 hours 48 Stone In CBD

13. Mastracci/Marcaccio 2005 Predictors of Choledocholithiasis Abboud et al 1999 Metaanalysis LR of CBD Stone with history of recent pancreatitis is 2.1 LR of CBD stone with history of hyperamylasemia is 1.5

14. Mastracci/Marcaccio 2005 SUMMARY: Question 1 Stones cause pancreatitis Stones frequently pass spontaneously Incidence of identifying CBD calculi decreases with time from onset of symptoms Clearance of stones from CBD correlates with relief of symptoms

15. Can we alter the course of an episode gallstone pancreatitis by treating a common bile duct stone?

16. Mastracci/Marcaccio 2005 CBD Stones Kelly 1982 Pre-ERCP Era Early treatment (<48h) had a higher mortality rate than late treatment (where incidence of CBD stones less) Risk of laparotomy outweighed the benefit of removing the CBD stone. In the ERCP Era, the issue was revisited because of the perceived lower risk of the procedure.

17. Mastracci/Marcaccio 2005 CBD Stones Kelly et al Randomized controlled trial Ranson�s score > 3 = higher mortality if submitted to pancreatic surgery early in their clinical course. Certainly any opportunity to alter the natural history of the disease has large clinical implications, 10% of patients with acute gallstone pancreatitis develop cholangitis <Neoptolomous, 1987> Mortality of this disease is estimated at 10 �15% <UK guidelines> Certainly any opportunity to alter the natural history of the disease has large clinical implications, 10% of patients with acute gallstone pancreatitis develop cholangitis <Neoptolomous, 1987> Mortality of this disease is estimated at 10 �15% <UK guidelines>

18. Mastracci/Marcaccio 2005 �Severity of Disease Neoptolomos et al Statistically significant decrease in LOS for patients with predicted severe pancreatitis who were offered urgent ERCP+ES, if a stone was found and removed. Trend for lower incidence of complications and mortality in the severe group who underwent urgent intervention. When the patients with a biliary tract indication for ERCP are removed there is no significant difference between early and late treatment. Also demonstrated that there is no increased risk of complications from the ERCP itself. Only biliary indications found improvementOnly biliary indications found improvement

19. Mastracci/Marcaccio 2005 CBD Stones Fan et al. There was a non-significant trend of decreased mortality in severe pancreatitis for patients who had urgent intervention. When gallstone pancreatitis subgroup is analyzed, the only benefit is seen in patients with biliary tract indication for ERCP Certainly any opportunity to alter the natural history of the disease has large clinical implications, 10% of patients with acute gallstone pancreatitis develop cholangitis <Neoptolomous, 1987> Mortality of this disease is estimated at 10 �15% <UK guidelines> Certainly any opportunity to alter the natural history of the disease has large clinical implications, 10% of patients with acute gallstone pancreatitis develop cholangitis <Neoptolomous, 1987> Mortality of this disease is estimated at 10 �15% <UK guidelines>

20. Mastracci/Marcaccio 2005 CBD Stones Folsch et al 238 Patients with no biliary obstruction randomized to early ERCP (126) or later ERCP if biliary symptoms presented (112) 58 patients in early group had a stone present, which was removed 22 patients in observation group developed a biliary indication for ERCP ? 13 had CBD stone Early group had more respiratory failure (p<0.03) Overall mortality within three months was 11% in the early group, 6% in the observation group (NSS) A policy of early ERCP and ES does not benefit patients with acute pancreatitis but no biliary indication. Did not substratefy mild vs. severe pancreatitis

21. Mastracci/Marcaccio 2005 CBD Stones Acosta and Pelligrini JACS August 1997 Experimental and clinical evidence that the duration of stone impaction correlates with the severity of pancreatitis. Major complications of pancreatitis were rare if the stone passed in <48 hours Observational study Severity was determined by appearance of pancreas at exploration. Observational study Severity was determined by appearance of pancreas at exploration.

22. Mastracci/Marcaccio 2005 CBD Stones Borie et al Systematic review Surgical Endoscopy Aug 2003 When biliary indications are excluded, the complication rates are no different with or without ERCP There is no evidence to support ES in severe pancreatitis if no stone was present

23. Mastracci/Marcaccio 2005 Summary: Question 2 The literature is confusing because of heterogeneous populations with differing indications for ERCP If there is no biliary cause, there is NO proof the early ERCP/ES modifies the course of pancreatitis in a stable patient (modify the course of pancreatitis vs. treating a biliary complication i.e.. cholangitis) (modify the course of pancreatitis vs. treating a biliary complication i.e.. cholangitis)

24. Mastracci/Marcaccio 2005 Summary Question 2 There may be a benefit in a patient with severe pancreatitis who is deteriorating Little to loseLittle to lose

25. Mastracci/Marcaccio 2005 Recommendation In Patients with acute pancreatitis and Biliary indications for ERCP, intervention should be undertaken at the time the biliary indication manifests. It may be reasonable to carry out ERCP for removal of a suspected CBD stone in a patient with Severe pancreatitis who is deteriorating. (Little to lose?)

26. In a mild course of GSP which has settled, do we need to worry about potential common duct stones at the time of LC? At tiem of definitive treatmentAt tiem of definitive treatment

27. Mastracci/Marcaccio 2005 Potential CBD Stones No studies relating to patients with pancreatitis alone. Mickley and Reisman In patients with known or clinically suspected CBD stones, clinical symptoms develop in 100% patients in 5 years.

28. Mastracci/Marcaccio 2005 Potential CBD Stones Peel et al. Retrospective review Untreated CBD stones developed clinical symptoms in 90% 24-45% caused serious complications cholangitis or pancreatitis

29. Mastracci/Marcaccio 2005 Potential CBD Stones Mills et al. Review of 8 series Average incidence of stones = 2.5% In patients without IOC, 0.03 to 0.8% later presented with symptomatic stones In all comers The metaanalysis is from routine and selective group Substratefied� In all comers The metaanalysis is from routine and selective group Substratefied�

30. Mastracci/Marcaccio 2005 Potential CBD Stones Abboud et al Metaanalysis History of pancreatitis Likelihood Ratio of finding a stone = 2.1 Similar incidence in Barkun et al Kelly et al Swiesinger et al.

31. Mastracci/Marcaccio 2005 Summary History of pancreatitis has a Positive predictive value of 2-8% for presence of a CBD stone High likelihood that this type of CBD stone will cause future morbidity

32. Mastracci/Marcaccio 2005 Recommendation We should investigate and treat potential CBD stones in this group of patients whenever possible

33. In resolving, uncomplicated pancreatitis, what is the appropriate management of potential CBD stones?

34. Mastracci/Marcaccio 2005 Managing Potential CBD Stones There are no studies specific to the gallstone pancreatitis population Extrapolate from the general CBD stone literature Debate: pre-op ERCP vs. planned IOC, and stone removal by various methods

35. Mastracci/Marcaccio 2005 Open Era Evidence Voluminous literature Four randomized trials All favoured one stage OC/IOC/OCBDE over pre op ERCP and OC Neoptolemos and Carr-Locke 55 preop ERCP = 3.6% mortality 59 one stage OR = 1.7% mortality

36. Mastracci/Marcaccio 2005 Laparoscopic ERA Sees et al LC/OCBDE shorter LOS than preop ERCP/LC ? ERCP pancreatitis Cuschieri et al European Collaborative Trial LC/IOC +/- LCBDE superior to pre op ERCP/LC Also Rhodes et al., Sqourakis et al.

37. Mastracci/Marcaccio 2005 Laparoscopic ERA Tse, Barkun et al Decision analysis model High risk = Pre op ERCP Criteria: (>80% likelihood CBD stone) Medium risk (includes history of pancreatitis) = LC/IOC; LCBDE, post op ERCP or OCBDE if stone identified Low risk = no imaging of duct Also: Urbach et al (2001)

38. Mastracci/Marcaccio 2005 Summary: Question 4 No evidence to support pre-operative ERCP in this group

39. Mastracci/Marcaccio 2005 Recommendation IOC should be done Decision for LCBDE or post op ERCP or OCBDE should depend on local expertise It is imperative that all general surgeons learn LCBDE to offer our patients the best care.

40. What is the best timing for LC as definitive treatment after an episode of gallstone pancreatitis?

41. Mastracci/Marcaccio 2005 Timing of Surgery Osbourne / Tandelli BJS ~ 1960 Recommended OC prior to hospital discharge because early risk of recurrent pancreatitis Kelly 1988 RCT OC </= 3 days after onset vs. >/= 3 days but before discharge Higher mortality (3.3 vs. 0%) and morbidity (48 vs. 11.3%) with early surgery

42. Mastracci/Marcaccio 2005 Timing of Surgery Uhl et al. Surgical Endoscopy 1999 Review 5 series: Recurrent pancreatitis in 29 � 63% if discharged without cholecystectomy Get theses references and determine trime frameGet theses references and determine trime frame

43. Mastracci/Marcaccio 2005 Timing of Surgery Barkun et al. 1994 35 patients pre-laparoscopic era Average time to surgery 9.9 days Complications while waiting for surgery = 0 58 patients Early laparoscopic era Average time to surgery 39.3 days Complications while waiting: 1x cholangitis 2x acute cholecystitis 3x recurrent pancreatitis Recommended LC on initial hospitalization When the though wast that early lc was dangerousWhen the though wast that early lc was dangerous

44. Mastracci/Marcaccio 2005 Risk of Conversion Borie et al. Review of 5 Series -- LC Early operation and >3 Ranson�s criteria were associated with increased conversion rate Operated too early�Operated too early�

45. Mastracci/Marcaccio 2005 Timing of Surgery Pelligrini AJS (vol 165) -- 1994 NIH Consensus conference Optimum time 5-6 days following onset of pancreatitis

46. Mastracci/Marcaccio 2005 Summary Discharge without cholecystectomy results in a significant rate of complications while waiting. LC on the same admission does not result in a significant increased conversion rate if performed when the pancreatitis has settled

47. Mastracci/Marcaccio 2005 Recommendation LC and IOC should be carried out prior to discharge as soon as the pancreatitis has settled.

48. What is the relative value of ES or LC as definitive treatment to prevent recurrent acute pancreatitis?� Switch with question sixSwitch with question six

49. Mastracci/Marcaccio 2005 Definitive Treatment It is generally accepted that a definitive treatment is required after an acute episode of biliary pancreatitis to decrease the incidence of recurrent gallstone pancreatitis by removing the supply of gallstones from the biliary tree. A patient who has had previous gallstone pancreatitis has a 30% chance of recurrent episode. Uhl 1999 Look for the quote for the 30% within 60 daysLook for the quote for the 30% within 60 days

50. Mastracci/Marcaccio 2005 Definitive Treatment LC has been the mainstay of treatment, however, some patients are at higher risk for complications of surgical intervention because of comorbidities In this group of people, an alternative option is ES after clearance of the bile duct, as it has been shown to be safe in people with high anesthesiological risk <Pezzilli et al>

51. Mastracci/Marcaccio 2005 � There are no randomized controlled trials investigating the efficacy of endoscopic sphincterotomy as definitive treatment after acute biliary pancreatitis Some groups have reported on their experience Significant heterogeneity with respect to study design and patient population

52. Mastracci/Marcaccio 2005 Definitive Treatment

53. Mastracci/Marcaccio 2005 Definitive Treatment Total number of patients = 424 (ERCP + ES without planned cholecystectomy) Weighted averages: Percentage who experienced recurrent pancreatitis = 2.8%. Incidence of recurrent biliary symptoms = 25.1% The number requiring subsequent cholecystectomy = 24.5%. Put cholecystectomy study� Risk of recurrent pancreatitis after cholecystectomy Put cholecystectomy study� Risk of recurrent pancreatitis after cholecystectomy

54. Mastracci/Marcaccio 2005 LC as Definitive Treatment Hui et al. 2004 Adding LC to ES did not further reduce the risk of pancreatitis in patients with CBD and GB stones 0% incidence of recurrent pancreatitis after LC in patients with GB stones

55. Mastracci/Marcaccio 2005 Summary LC is better protection than ES ES is viable option in patients in whom the surgical risk outweighs the increased protection of LC

56. Mastracci/Marcaccio 2005 Recommendation LC should be performed whenever possible to protect against subsequent pancreatitis and complications

57. In Summary�

58. Mastracci/Marcaccio 2005 Summary Stones cause pancreatitis Stones frequently pass spontaneously Incidence of identifying CBD calculi decreases with time from onset of symptoms Clearance of stones from CBD correlates with relief of symptoms

59. Mastracci/Marcaccio 2005 Summary If there is no biliary cause, there is NO proof the early ERCP/ES modifies the course of pancreatitis in a stable patient

60. Mastracci/Marcaccio 2005 Summary There may be a benefit to Urgent ERCP in a patient with severe pancreatitis who is deteriorating Little to loseLittle to lose

61. Mastracci/Marcaccio 2005 Summary History of pancreatitis has a Positive predictive value of 2-8% for presence of a CBD stone High likelihood that this type of CBD stone will cause future morbidity

62. Mastracci/Marcaccio 2005 Summary No evidence to support pre-operative ERCP in patients with a history of pancreatitis.

63. Mastracci/Marcaccio 2005 Summary No evidence to support pre-operative ERCP in patients with a history of pancreatitis.

64. Mastracci/Marcaccio 2005 Summary Discharge without cholecystectomy results in a significant rate of complications while waiting. LC on the same admission does not result in a significant increased conversion rate if performed when the pancreatitis has settled

65. Mastracci/Marcaccio 2005 Summary LC is better protection than ES ES is viable option in patients in whom the surgical risk outweighs the increased protection of LC

66. Mastracci/Marcaccio 2005 Recommendation In Patients with acute pancreatitis and Biliary indications for ERCP, intervention should be undertaken at the time the biliary indication manifests. It may be reasonable to carry out ERCP for removal of a suspected CBD stone in a patient with Severe pancreatitis who is deteriorating. (Little to lose?)

67. Mastracci/Marcaccio 2005 Recommendation We should investigate and treat potential CBD stones in patients who have had GSP whenever possible

68. Mastracci/Marcaccio 2005 Recommendation IOC should be done Decision for LCBDE or post op ERCP or OCBDE should depend on local expertise It is imperative that all general surgeons learn LCBDE to offer our patients the best care.

69. Mastracci/Marcaccio 2005 Recommendation LC and IOC should be carried out prior to discharge as soon as the pancreatitis has settled.

70. Mastracci/Marcaccio 2005 Recommendation LC should be performed whenever possible to protect against subsequent pancreatitis and complications

71.