Biliary pancreatitis

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by Bushra Ibnauf as part of SAMA's Visiting Faculty Program in Salam Rotana Hotel on June 24th 2011. This was in collaboration with the Sudanese Society for Gastroenterology.

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Biliary pancreatitis

  1. 1. Acute Biliary Pancreatitis: Pathogenesis and Management Bushra Ibnauf Sulieman, MD MS Consultant, Gastroenterology & Hepatology Department of Medicine King Faisal Specialist Hospital & Research Center - Jeddah
  2. 2. Case <ul><li>63 y.o. woman is admitted with abdominal pain, nausea and vomiting x 48 hours </li></ul><ul><li>No cardiopulmonary disease </li></ul><ul><li>Labs: </li></ul><ul><ul><li>WBC 18,500, HGB 13, PLT 191,000 </li></ul></ul><ul><ul><li>ALT 330, AST 260, ALKP 250, Bili 1.4, glucose 225 </li></ul></ul><ul><ul><li>BUN 47, Cr 1.4, PT 12s </li></ul></ul><ul><li>Ultrasound </li></ul><ul><ul><li>Gallstones in gallbladder </li></ul></ul><ul><ul><li>CBD 5mm without stones </li></ul></ul>
  3. 3. Objectives <ul><li>Pathogenesis: </li></ul><ul><li>Gallstone and biliary sludge </li></ul><ul><li>Biliary pancreatitis </li></ul><ul><li>Acute biliary pancreatitis </li></ul><ul><li>Diagnosis </li></ul><ul><li>Outcome </li></ul><ul><li>Management </li></ul><ul><ul><li>Medical </li></ul></ul><ul><ul><li>ERCP  sphincterotomy </li></ul></ul><ul><ul><li>Cholecystectomy </li></ul></ul>
  4. 4. Types of Gallstones Feldmans GastroAtlas online; www.gastroatlas.com
  5. 6. Gallstone Pathogenesis Feldman: Sleisenger & Fordtran's Gastrointestinal and Liver Disease, 7th ed., page 1069
  6. 7. Bile Supersaturation <ul><li>Cholesterol solubilization in bile </li></ul><ul><ul><li>Micelles and mixed micelles </li></ul></ul><ul><ul><li>Gallstone formation = maximal effective solubility is reached </li></ul></ul><ul><li>Mechanisms </li></ul><ul><ul><li> bile acids loss = Crohn’s, ileal resection, bypass </li></ul></ul><ul><ul><li> GB cholesterol secretion = obese white </li></ul></ul>Schiff: Diseases of the liver. 1 st edition, page 427-447 Feldmans GastroAtlas online; www.gastroatlas.com
  7. 8. Gallstone Nucleation <ul><li>Nucleation time </li></ul><ul><ul><li> in patients with gallstones </li></ul></ul><ul><li>Pro-nucleating factors </li></ul><ul><ul><li>Mucin glycoprotein – bind Ca-bilirubinate, bile salts, inorganic salts </li></ul></ul><ul><ul><li>IgG and IgM, aminopeptidase N haptoglobin, α1-acid glycoprotein </li></ul></ul><ul><li>Anti-nucleating factors </li></ul><ul><ul><li>Apolipoprotein A-I/A-II </li></ul></ul><ul><ul><li>Multilamellar vesicles </li></ul></ul>Schiff: Diseases of the liver. 1 st edition, page 427-447
  8. 9. Gallbladder Hypomotility <ul><li>Motility defects in gallstone patients </li></ul><ul><ul><li> fasting and residual volume </li></ul></ul><ul><ul><li> contractile response to intravenous CCK </li></ul></ul><ul><ul><li>Slower gallbladder emptying with meals </li></ul></ul><ul><ul><li>Cause = ?? Hormonal </li></ul></ul><ul><li>End result = stasis  sludge </li></ul>Schiff: Diseases of the liver. 1 st edition, page 427-447 Feldman: Sleisenger & Fordtran's Gastrointestinal and Liver Disease, 7th ed., page 1071
  9. 10. Pigment Stone Pathogenesis Feldmans GastroAtlas online; www.gastroatlas.com
  10. 11. Gallstone Risk Factors Am Fam Physician 2000; 62:164-74.
  11. 12. Gallstone Complications Feldman: Sleisenger & Fordtran's Gastrointestinal and Liver Disease, 7th ed., page 1074
  12. 13. Pathogenesis of ABP <ul><li>Bernard 1856 </li></ul><ul><ul><li>Bile induces pancreatitis in animals </li></ul></ul><ul><li>Opie 1902 </li></ul><ul><ul><li>Common channel hypothesis </li></ul></ul>Current Gastroenterology Reports 2003; 5:125-132
  13. 14. <ul><li>50% cases of pancreatitis </li></ul><ul><ul><li>Gallstones </li></ul></ul><ul><li>Stones recovered in stool </li></ul><ul><ul><li>85-90% with ABP compared to 10% w/ symptomatic cholelithiasis w/out panc </li></ul></ul><ul><li>Early surgical series </li></ul><ul><ul><li>w/in 48 hours </li></ul></ul><ul><ul><li>60-80% incidence of CBD or ampullary stones in ABP </li></ul></ul>Pathogenesis of ABP Gastroenterology 2003; 125:229-235 Feldmans GastroAtlas online; www.gastroatlas.com
  14. 15. Diagnosis of ABP <ul><li>Factors suggestive of ABP </li></ul><ul><ul><li>Gallbladder stones </li></ul></ul><ul><ul><li>Cholangitis complicating ABP </li></ul></ul><ul><ul><li>Amylase >1000 IU/L </li></ul></ul><ul><li>Tenner et al. </li></ul><ul><ul><li>Large meta-analysis of 8 studies, 557 patients </li></ul></ul><ul><ul><li>ALT > 3X ULN = ppv of > 95% </li></ul></ul><ul><ul><li>AST, ALKP, bili = 3X ULN have ppv < 90% </li></ul></ul>Am J Gastroenterol. 1994; 89(10)1863-1866
  15. 16. Diagnosis of ABP <ul><li>Ultrasound </li></ul><ul><ul><li>GB stones = 95% sensitivity, 98% specificity </li></ul></ul><ul><ul><li>Acute pancreatitis = 60-80% sensitivity </li></ul></ul><ul><ul><li>CBD stones = 25-90% sensitivity, 90-95% specificity </li></ul></ul><ul><ul><li>Lack of CBD dilation does not exclude acute BP </li></ul></ul><ul><ul><li>CT </li></ul></ul><ul><ul><li>Gold standard for assessment of </li></ul></ul><ul><ul><li>pancreatic involvement </li></ul></ul><ul><ul><li>- Low sensitivity for cause </li></ul></ul>Gastroenterology 2003; 125:229-235
  16. 17. <ul><li>MRCP </li></ul><ul><ul><li>Choledocholithiasis = 90-100% sensitivity, 92-100% spec </li></ul></ul><ul><ul><li>Not well suited for sick patients with ABP </li></ul></ul><ul><ul><li>Operator, facility dependent </li></ul></ul><ul><ul><li>ERCP </li></ul></ul><ul><ul><li>Utilization is ONLY for therapy </li></ul></ul>Feldmans GastroAtlas online; www.gastroatlas.com Diagnosis of ABP
  17. 18. http://www.medinfo.ufl.edu/year2/clinmed/jaundice/slide18.html Diagnosis of ABP
  18. 19. Severity Classification <ul><li>Scoring systems </li></ul><ul><ul><li>Ranson </li></ul></ul><ul><ul><li>Glasgow </li></ul></ul><ul><ul><li>Acute physiology and chronic health evaluation score (APACHE II) </li></ul></ul><ul><ul><li>Hong Kong score </li></ul></ul><ul><ul><li>New Haven </li></ul></ul><ul><ul><li>CRP, hemoconcentration </li></ul></ul><ul><li>Atlanta symposium (1992) </li></ul><ul><ul><li>Severe pancreatitis = organ failure and necrosis </li></ul></ul>Gastroenterology 2003; 125:229-235
  19. 20. Conservative Medical Therapy <ul><li>Fluid resuscitation </li></ul><ul><ul><li>immediate and aggressive </li></ul></ul><ul><ul><li>prevents progression to organ failure </li></ul></ul><ul><li>Pain control </li></ul><ul><li>Nutritional support </li></ul><ul><ul><li>Nasojejunal tubes = reduce septic complications </li></ul></ul><ul><ul><li>Intravenous nutrition (TPN) = less favorable </li></ul></ul><ul><li>Antibiotics </li></ul><ul><ul><li>Necrotizing pancreatitis </li></ul></ul><ul><ul><li>Cholangitis </li></ul></ul>Gastroenterology 2003; 125:229-235
  20. 21. Outcome in Pancreatitis <ul><li>Morbidity </li></ul><ul><ul><li>Majority present = mild disease, benign course </li></ul></ul><ul><ul><li>25% = severe attacks  sepsis </li></ul></ul><ul><li>Mortality </li></ul><ul><ul><li>ABP + biliary sepsis = 13-50% </li></ul></ul><ul><ul><li>Increased mortality with early biliary surgery (IOC + cholecystectomy + bile duct exploration) </li></ul></ul>Surgery 1980; 88:345-350 Gastroenterology 2003; 125:229-235 Type of Surgery No. of patients Mortality rate (%) Ampullary obstruction (%) Spontaneous stone passage (%) Early 24 12 63 14 Delayed 134 0 5 86 Elective 14 7 3 81
  21. 22. Challenge Identifying the patients who will benefit from early endoscopic drainage
  22. 23. ERCP and Sphincterotomy
  23. 24. ERCP
  24. 25. ERCP
  25. 26. ERCP – Advanced Transpappilary Balloon dilation Precut Sphincterotomy
  26. 27. ERCP Complications 5-30% <ul><li>Pancreatitis </li></ul><ul><li>Hemorrhage </li></ul><ul><li>Cholangitis </li></ul><ul><li>Perforation </li></ul><ul><li>Cardiopulmonary </li></ul><ul><li>Miscellaneous: Stent related </li></ul>
  27. 28. Major ERCP Complications Consensus Definition Complications of endoscopic biliary sphincterotomy. Freeman, Sherman NEJM 1996 Mild Moderate Severe Pancreatitis Hospital stay 2-3 days 4-10 days 10 days Pseudocyst/intervention Bleeding Hgb drop<3gm No Transfusion Transfusion<4 U No angio/surgery Transfusion >5 U Angio/surgery Perforation Possible or very mild Definite, treated medically Medical Rx>10 days, intervention Infection (Cholangitis) >38C for 24-28 hrs Febrile or septic illness > 3 days hospital Septic shock or surgery
  28. 29. Post-ERCP pancreatitis-Risk Factors Multivariate Analysis Risk factors for post-ERCP pancreatitis. Freeman, DiSario GIE 2001 Definite Maybe No Suspected SOD Female sex Biliary sphincterotomy Young Age Acinarization Small CBD Difficult/failed cannulation Trainee involvement SOD manometry Pancreatic sphincterotomy Absence of CBD stone PD injection Lower ERCP volume History of PEP Balloon Dilation Normal Bilirubin Precut sphincterotomy
  29. 30. ERCP Bleeding-Risk Factors Multivariate Analysis Risk factors for post-ERCP pancreatitis. Freeman, DiSario GIE 2001
  30. 31. Reducing Complications: Cannulation
  31. 32. Reducing Complications: Cannulation
  32. 33. Complications: Management Pancreatic stent placement Post-sphincterotomy Bleeding hemoclipping
  33. 34. ERCP  Sphincterotomy <ul><li>Four studies = randomized, placebo controlled, blinded studies </li></ul><ul><ul><li>United Kingdom (1988) </li></ul></ul><ul><ul><li>Hong Kong (1993) </li></ul></ul><ul><ul><li>Poland (1995) * abstract only* </li></ul></ul><ul><ul><li>Germany (1997) </li></ul></ul><ul><li>One = meta-analysis </li></ul><ul><ul><li>United States (1999) </li></ul></ul>Lancet 1988; 2:979-983 N Eng J Med 1993; 328:228-232 Gastroenterology 1995; 108:A380(abstract) N Eng J Med 1997; 336:237-242 Am J Gastroenterol 1999; 94:3211-3214
  34. 35. Trials of ERCP in ABP Lancet 1988; 2:979-983 N Eng J Med 1993; 328:228-232 N Eng J Med 1997; 336:237-242 Gastroenterology 1995; 108:A380(abstract) ERCP  ES Control Time to ERCP Center Severe pancreatitis ERCP Success Gall-stones Other United Kingdom 1988 59 62 72h Single 44% Glasgow 88% 85% Hong Kong 1993 97 98 24h Single 42% Ranson’s 90% 66% Germany 1997 126 112 72h Pain onset Multiple 14% Glasgow 96% 46% Bili > 5 excl Poland 1995 178 102 24h Single NR NR NR Pooled 460 374 30% 92% 61%
  35. 36. <ul><li>U.K study </li></ul><ul><li>LOHS 9.5 vs 17d (ERCP/ES vs controls; p=0.03) </li></ul><ul><li>Hong Kong study </li></ul><ul><li>Biliary sepsis reduced 0/30 vs 8/28 (ERCP/ES vs controls; p<0.001) </li></ul><ul><li>Polish Study </li></ul><ul><li>Published in abstract only </li></ul><ul><li>German study </li></ul><ul><li>Patients with severe pancreatitis had more severe complications and resp. failure </li></ul><ul><li>Many criticisms </li></ul>Predicted mild pancreatitis Predicted severe pancreatitis P<0.05 P=0.01 P=0.003 P<0.05 Lancet 1988; 2:979-983 N Eng J Med 1993; 328:228-232 Gastroenterology 1995; 108:A380(abstract) N Eng J Med 1997; 336:237-242
  36. 37. Predicted mild pancreatitis P<0.05 Predicted severe pancreatitis Lancet 1988; 2:979-983 N Eng J Med 1993; 328:228-232 Gastroenterology 1995; 108:A380(abstract) N Eng J Med 1997; 336:237-242 Interval between onset of ABP and ES Polish Study
  37. 38. Metanalysis of ERC+ES in ABP <ul><li>ARR for mortality </li></ul><ul><li>Pooled NNT = 25.6 </li></ul>ARR for morbidity Pooled NNT = 7.6 Am J Gastroenterol 1999; 94:3211-3214
  38. 39. Consensus Recommendation NIH State-of-the-science Conference, January 2002 <ul><li>Table 3. Indications for ERCP in biliary pancreatitis </li></ul><ul><li>Before cholecystectomy </li></ul><ul><li>Concomitant cholangitis </li></ul><ul><li>Obstructive Jaundice </li></ul><ul><li>Severe disease </li></ul><ul><li>In-hospital exacerbation </li></ul><ul><li>After cholecystectomy </li></ul><ul><li>Unsuccessful laparoscopic/open common bile duct exploration </li></ul><ul><li>Smoldering disease  sphincter dysfunction/ductal disruption </li></ul>“ In summary, ERCP plays a distinct role in the very ill patient with acute biliary pancreatitis…” Gastrointest Endosc 2002; 56(6):S170-S174
  39. 40. Case <ul><li>63 y.o. woman is admitted with abdominal pain, nausea and vomiting x 48 hours </li></ul><ul><li>ERCP – 5mm stone distal common bile duct </li></ul><ul><li>Biliary sphincterotomy </li></ul><ul><li>Clinical improvement over the next three days </li></ul><ul><li>What next? </li></ul>
  40. 41. Follow-up Cholecystectomy? <ul><li>Kelly. Surgery. 1980; 88:345-350. </li></ul><ul><ul><li>(n=14) Resolved pancreatitis, elective cholecystectomy </li></ul></ul><ul><ul><li>38% with recurrent ABP </li></ul></ul><ul><ul><li>Surgical mortality rate of 7% </li></ul></ul><ul><li>Osborne et al . Br. J. Surg. 1981; 68:758-761. </li></ul><ul><ul><li>(n=37) resolved pancreatitis + chole = mortality 0% </li></ul></ul><ul><ul><li>(n=10) unresolved pancreatitis + chole = mortality 50% </li></ul></ul><ul><ul><li>(n=100) resolved pancreatitis d/c without chole = recurrent attacks of ABP 21%, elective surgery no complications in 43% </li></ul></ul>
  41. 42. Follow-up Cholecystectomy? <ul><li>Amsterdam group </li></ul><ul><li>120 surgically fit patients </li></ul><ul><li>Documented GB stones and/or CBD stones + ES w/ stone extraction </li></ul><ul><li>Chole w/in 6weeks of ERCP or wait-and-see approach </li></ul>Median f/u = 30 mo Lancet 2002 360; 760-765
  42. 43. ERCP/ES Alone <ul><li>Median age 78 </li></ul><ul><li>Age>70 in 38/51 </li></ul>CBD stone(s) 38/51 Mean F/U 27 mo Gut 1995; 37:119-120
  43. 44. Biliary Sludge <ul><li>Biliary colic ~ 10% </li></ul><ul><li>Acute pancreatitis ~ <1-5% </li></ul><ul><li>All patients w/ </li></ul><ul><ul><li>Non-alcoholic pancreatitis ~ 30% have sludge </li></ul></ul><ul><ul><li>Idiopathic pancreatitis ~ 74% have sludge </li></ul></ul>Ann Intern Med 1999; 130:301-311 Feldmans GastroAtlas online; www.gastroatlas.com
  44. 45. ABP and Biliary Microlithiasis <ul><li>Komut et al. Gatrointest Endosc 2001;54:37-41 </li></ul><ul><ul><li>N=15 w/ suspected biliary AP </li></ul></ul><ul><ul><li>All underwent ERCP/ES < 24h </li></ul></ul><ul><ul><li>Exclusions: </li></ul></ul><ul><ul><ul><li>gallstones on U/S and ERCP </li></ul></ul></ul><ul><ul><ul><li>other cause of AP. </li></ul></ul></ul><ul><ul><li>Microlithiasis (Ca bilirubinate granules 75%) in 80% pts. </li></ul></ul><ul><ul><li>No episodes of ABP in f/u (mean 30 months) </li></ul></ul><ul><ul><li>2 patients developed GB stones, one required lap chole </li></ul></ul>
  45. 46. Summary <ul><li>ERCP and sphincterotomy in all patients with ABP remains controversial </li></ul><ul><li>ERCP and sphincterotomy appears to benefit patients with severe pancreatitis </li></ul><ul><ul><li>decreased morbidity </li></ul></ul><ul><ul><li>?? Mortality </li></ul></ul><ul><li>Same admission cholecystectomy is recommended </li></ul><ul><li>Biliary microlithiasis is present in many patients with ABP </li></ul>
  46. 47. Acute Gallstone Pancreatitis Mild Severe Cholecystectomy (same admit) Cholecystectomy (same admit) Discharge ERCP/ES ERCP/ES No planned cholecystectomy Clinical deterioration Emergent Cholangitis Jaundice BD dilated Surgical Contraindication(s) Adapted From - Gastrointest Endosc 2002; 56(6):S170-S174
  47. 48. Biliary Sludge Sx’s or complications present Consider cholecystectomy No reversible factor present Reversible factor present (ceftriaxone) Surgical candidate? Nonsurgical therapy (UDCA, cholecystostomy) Sx’s or complications absent Reverse (if possible) , observation Clinical observation Reconsider cholecystectomy if sludge persists or complications develop Yes No
  48. 49. SAMA www.sama-sd.org

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