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Acute biliary pancreatitis

Tomasz Marek. Acute biliary pancreatitis. 6th EAGE Postgraduate School in Gastroenterology Prague 2010. Department of Gastroenterology & Hepatology Medical University of Silesia in Katowic e, Poland. Acute biliary pancreatitis. Pathogenesis Diagnosis Determination of etiology

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Acute biliary pancreatitis

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  1. Tomasz Marek Acutebiliarypancreatitis 6th EAGEPostgraduateSchoolinGastroenterology Prague 2010 Department of Gastroenterology & Hepatology MedicalUniversity of Silesia inKatowice, Poland

  2. Acutebiliarypancreatitis • Pathogenesis • Diagnosis • Determination of etiology • Prognosis • Endoscopictreatment

  3. Pathogenesis of biliarypancreatitis Opie, Bull John Hopkins Hosp 1901

  4. Pathogenesis of biliarypancreatitis Acutebiliarypancreatitis (ABP) istriggered byobstruction of theampulla of Vater by migratingorimpactedstones Common channel? Obstruction !!! Opie, Bull John Hopkins Hosp 1901 Acosta & Ledesma, NEJM 1974

  5. Pathogenesis of biliarypancreatitis

  6. Diagnosis of ABP

  7. Diagnosis of ABP • Pain • Elevatedenzymes- lipasebetterthanamylase- no specificcut-off, 2-3 x N ? • Imagingstudies- usually not necessary- US not perfect (intestinal gas)- CT should not be donewithin 72hif not for differentialdiagnosis

  8. Determination of biliaryetiology

  9. Determination of biliaryetiology • Elevated liverfunction tests(~ 2 x N) • Gallstones or sludge (?) • Dilated CBD (> 8 mm) • ERCP (added value):- small CBD stones in non-dilated CBD- endoscopic signs of stone passage- biliarymicrolithiasis

  10. CBD imagingin ABP • Abdominal US not sensitive enough • MRCP- small (especially impacted) stones may be missed- air bubbles may give false+ results- fluid collections may obscure CDB in severe cases • EUS- may be not readily available 24/24h (ES delay?)- perfect when ERCP fails

  11. Determination of biliaryetiology CBD stones 326 (39.8%)1 pt lab criterianegative Gallbladderstonesonly 402 (49.0%)24 pts lab criterianegative ? Biliarymicrolithiasis 19 ( 2.3%) Signs of stonepassage 31 ( 3.8%) Lab criteriaonly 42 ( 5.1%)

  12. ABP prognosis

  13. ABP prognosis • Smalldifferences • Glasgow Blamey- best of „classic” systems • Bilirubin to be removedfrom AP III J • CRP cut-offto be set higher180 mg/l worksbetterthan 150 mg/l • ERCPcan be used for prognosiswhendone for treatment

  14. ABP treatment

  15. ABP treatment • Obstructionisthemain elementof thepathogenesis of ABP • The restoration of normal outflowof bile and pancreatic juiceshouldconstitute an effective, cause-directed treatmentof acute biliary pancreatitis • Endoscopic sphincterotomycould be the method of choice

  16. ES for ABP – First cases

  17. ABP treatment • Itisthegreatestpleasureof theendoscopistto removeimpactedstoneinpatientwithacutepancreatits

  18. ABP treatment

  19. ERCP / ES for ABP Randomizedcomparisonsof endoscopicsphincterotomy (ES)versusconventional management (CM)for acutebiliarypancreatitis 1988 - Neoptolemos et al., Leicester, UK (Lancet) 1993 - Fan et al., Hong-Kong, Hong-Kong (NEJM) 1995 - Fölsch et al., Kiel, Germany (NEJM) (multicenterstudy) 2006 – Acosta et al., Los Angeles, USA (Ann Surg) 2007 - Oriaet al., Buenos-Aires, Argentina (Ann Surg)

  20. ERCP / ES for ABP – Neoptolemos et al. • 121 patients (62 CM, 59 ERCP) • ERCP / ES > 48 & < 72 h Complications Mortality ABP PredictedmildPredictedsevereTotal CM 12%61%34% ERCP 12%24%17% CM 0%18% 8% ERCP 0% 4% 2% • ERCP only after 48 hours (severity stratification) • ES onlyinpatientswith CBD stones(33% ERCP) • Trend onlyobserved for mortality Neoptolemos et al., Lancet 1988

  21. ERCP / ES for ABP – Fan et al. • 195 patients, 127 ABP (64 CM, 63 ERCP) • ERCP / ES < 24 h Complications Mortality ABP PredictedmildPredictedsevereTotal CM 17%54%33% ERCP 18%13%16% CM 0%18% 8% ERCP 0% 3% 2% • ESonlyinpatientswith CBD stones (38% ERCP) • Significantreduction of biliarysepsisin ES group • Trend onlyobserved for mortality Fan et al., NEJM 1993

  22. ERCP / ES for ABP – Fölsch et al. • 238 patients, (112 CM, 126 ERCP) • ERCP / ES < 72 h Complications Mortality ABP Total CM 51%11% ERCP 46%1% CM 4% ERCP 8% New onsetjaundice • Exclusion of patientswithjaundice (Bil > 5.0 mg/dL) • ES only in CBD stones (46% ERCP / 12% CM group) • Fewcases/center; ERCP mortality 5xvs. UK / HK Folschet al., NEJM 1995

  23. ERCP / ES for ABP – Acosta et al. • 61 patients (31 CM, 30 ERCP) • ERCP / ES > 24 h & < 48 h of onset Complications Mortality ABP Total CM 29% ERCP 7% CM 0% ERCP 0% • Complicated design • Patienswithobstruction (Bil ↓ checkedevery 6h) • ERCP for patientswith no spontaneousdisobstruction • ES – ERCP 43% < 48 h, CM 10% > 48 h Acosta et al., Ann Surg 2006

  24. ERCP / ES for ABP – Oria et al. • 238 patients, 102 randomized (51 CM, 51 ERCP) • ERCP / ES > 24 h of onset Complications Mortality ABP Total CM 18% ERCP 21% CM 2% ERCP 4% • Bil >=1.2 mg/dL + CBD >= 8mm on US • Acutecholangitis (temp >= 38.4 C) excluded • ES 76% ERCP group (CBDS) • No differencein organ failurescore Oriaet al., Ann Surg 2007

  25. ERCP / ES for ABP – Guidelines AOC JaundiceSev AP Old/unfit • Atlanta ’94 X X • BSG ’98 X XX • SSAT ’98 X • Santorini ’99 X XX • SNFGE ’01 X X • WCG ’02 X XXX • JSAEM ’02 X XX • IAP ’03 X X • BSG ’05 X XXX • ACG ’06 X XX? X • AGA ’07 X XX? X

  26. ERCP / ES for ABP – Guidelines • Allguidelinesrecommendthe use of ERCP/ESin settings with high suspicion of CBD stones,jaundice and cholangitis • Majority of guidelines recommend ERCP/ESas an emergency procedure(as soon as possible) • Noguidelinesrecommendtheuseof ERCP/ES inpredictedmildpancreatitis(OK if the prognosis system is perfect and it can provide the prognosis on admission)

  27. Prediction of CBD stones n (793)% Time P-E (h) Bilirubin (mg/dL) ALT (U) ALP (U) GGT (U) Amylase (U) Lipase (U) CBD Ø (mm) IMPS 13116.5 % 32 5.2 413 314 710 2074 11866 13.2 CBDS 20626.0 % 37 3.4 350 259 571 1605 10020 11.7 no CBDS 45657.5 % 34 2.9 392 210 492 1415 8121 8.7 p 0.054 0.000 0.113 0.000 0.000 0.000 0.000 0.000

  28. Prediction of CBD stones – Bilirubin CBDS 33 (25%) 84 (26%) 38 (24%) 51 (28%) n (792) Bilirubin 0 - 1 mg/dL 1 - 3 mg/dL 3 - 5 mg/dL > 5 mg/dL IMPS 7 ( 6%) 32 (10%) 39 (24%) 53 (29%) no CBDS 90 (69%) 204 (64%) 85 (53%) 76 (42%)

  29. Prediction of CBD stones – CBD diameter CBDS 4 (11%) 50 (19%) 84 (28%) 54 (39%) n (740) CBD diameter 0 - 4 mm 5 - 8 mm 9 - 12 mm > 12 mm IMPS 1 ( 3%) 20 ( 7%) 44 (15%) 45 (33%) no CBDS 32 (87%) 199 (74%) 169 (57%) 38 (28%)

  30. Prediction of impactedstone – ES timing No IMPS 3 (60%) 35 (70%) 65 (76%) 518 (84%) n (759) Time: Pain – ERCP 0 – 6 h 6 – 12 h 12 – 18 h > 18 h IMPS 2 (40%) 15 (30%) 20 (24%) 101 (16%)

  31. Prediction of impactedstone – ES timing No IMPS 52 (68%) 185 (79%) 121 (87%) 263 (85%) n (759) Time: Adm – ERCP 0 – 2 h 2 – 4 h 4 – 6 h > 6 h IMPS 24 (32%) 49 (21%) 18 (13%) 47 (15%)

  32. Prediction of impactedstone – ES timing

  33. Prediction of acutecholangitis n (789)% Temp (C) Bilirubin (mg/dL) ALT (U) ALP (U) GGT (U) WBC (G/L) CRP (mg/L) CBD Ø (mm) no AOC 70389.1 % 37.5 3.1 388 228 527 12.4 51.8 9.7 AOC 8610.9 % 37.5 5.5 359 337 732 14.6 92.5 14.0 p 0.445 0.000 0.383 0.000 0.000 0.000 0.000 0.000

  34. ERCP / ES for ABP – ES for allpatients? • CBD stonesaredifficult to be predicted • ES inpatientswith no CBD stones ? • ES causesdecompression of pancreatic and bile ducts(papillary edema may develop after stone passage) • ES preventsthe repeatedobstruction of the papillatriggering the next episode of ABP • ES canlead to removal of possible ERC-invisible CBD stones (veryrare ~ 3%)

  35. ERCP / ES for ABP – Nowak et al. • 280 patients, 205 randomized (102 CM, 103 ERCP) • ERCP / ES < 24 h Complications Mortality ABP PredictedmildPredictedsevereTotal CM 25%74%38% ES 10%39%17% CM 5%33%13% ES 0% 4%2% • ES in 75 patients with impacted stone w/o random • ES in 100% of ES group (irrespective of CBD stones) • ES useful in both predicted mild and severe cases Nowak et al., Gastroenterology 1995 (abstract)

  36. ERCP / ES for ABP – Nowakowska et al. • 976 patients, 253 randomized (126 CM, 127 ERCP) • ERCP / ES < 12 h (median 5 h) Complications Mortality ABP Total CM 48% ES 25% CM 5% ES 1% • ES w/o random injaundice, AOC, CBD stones, etc. • ERCP for all, randomizationafternegative ERC • Stratification for gallbladderstones • ES 100% ES group Nowakowska et al., Gut 2010 (abstract)

  37. ERCP / ES for ABP – van Santvoort et al. • 78 patientswithcholestasis (26 CM, 52 ERCP) • ERCP / ES < 72 h fromonset Complications Mortality ABP Total CM 54% ES 25% CM 15% ES 6% • Patientswithsevere ABP from PROPATRIA study • Prospectivestudy, no randomization • Cholestasis (Bil > 2.3, CBD > 8 (10) mm) • ES 87% ERCP Van Santvoortet al., Ann Surg 2009

  38. ERCP / ES for ABP – Pooledanalysis 7 RCTs, 1107 patients, (547 CM, 560 ERCP) Complications Mortality Neoptolemos Fan Fölsch AcostaOria Nowak Nowakowska Total CM 34 % 33 % 51 % 29% 18 % 38 % 48 % 40 % ERCP 17 % 16 % 46 % 7% 22 % 17 % 25 % 25 % CM 8.2 % 7.9 % 3.6 % 0.0% 2.0 % 12.7 % 4.8 % 6.2 % ERCP 1.7 % 1.6 % 7.9 % 0.0% 3.9 % 2.2 % 0.8 % 2.9 %

  39. ERCP / ES for ABP – Pooledanalysis

  40. ERCP / ES for ABP – Pooledanalysis • Designstotallydifferent • Differententrycriteria • Differenttreatmentregimens • Differentoutcomecriteria

  41. ERCP / ES for ABP • May be difficult • Pre-cutnecessaryup to 35% • Failurerate: 69/820 (8.5%) • Safe – complications: 12 / 820 (1.5%) • Consumesextensive resourcesTeam on call: 3-5 doctors and nurses

  42. ERCP / ES for ABP in Katowice Year Q1 Q2 Q3 Q4 Tot P/Wk 2001 45 41 34 54 174 3.3 2002 44 49 46 73 212 4.1 2003 59 54 65 56 234 4.5 2004 71 76 65 47 259 5.0 P/Wk 4.2 4.2 4.0 4.4Weekly max: 15 cases (Mar 27 - Apr 2, 04)Daily max: 5 cases (Nov 16, 01) (8 additionaldays - 4 cases/d)

  43. Acute biliary pancreatitis - Summary • ABP is triggered by obstructionof major duodenal papilla by biliary stones • Rapid identification of biliary etiologyis of great importance • Urgent ERCP / ES decreases complicationsand mortality rates • As the CBD stones identification is not perfectand there is no time for severity assessmenturgent ES should be done in all patients with ABP

  44. ERCP for ABP prognosis

  45. ERCP for ABP prognosis No swelling Minor swelling,limited to peripapillaryarea Moderateswelling withextensive involvementof D2 Severe swellingwith extensiveinvolvementof D2, bluishdiscoloration DGE MUSK 2000-2005

  46. Duodenalswelling DGE MUSK 2000-2005

  47. Duodenalswelling Normal duodenum Deformed duodenal loop D2 deformed and narrowed DGE MUSK 2000-2005

  48. Duodenalswelling Edema of submucosal layer DGE & DPAT MUSK 2000-2005 Mucosal hyperemia

  49. Duodenalswelling Normal duodenum Marked thickening of D2 wall 20 mm DGE & DRAD MUSK, Helimed 2000-2005

  50. Duodenalswelling D2 swelling limited to antero-medial wall D2 swelling limited to peripapillary area DGE & DRAD MUSK, Helimed 2000-2005

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