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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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slide1

Tomasz Marek

Acutebiliarypancreatitis

6th EAGEPostgraduateSchoolinGastroenterology

Prague 2010

Department of Gastroenterology & Hepatology

MedicalUniversity of Silesia inKatowice, Poland

acute biliary pancreatitis
Acutebiliarypancreatitis
  • Pathogenesis
  • Diagnosis
  • Determination of etiology
  • Prognosis
  • Endoscopictreatment
pathogenesis of biliary pancreatitis
Pathogenesis of biliarypancreatitis

Opie, Bull John Hopkins Hosp 1901

pathogenesis of biliary pancreatitis1
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

diagnosis of abp1
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
determination of biliary etiology1
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
cbd imaging in abp
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
determination of biliary etiology2
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%)

abp prognosis1
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
abp treatment1
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
abp treatment2
ABP treatment
  • Itisthegreatestpleasureof theendoscopistto removeimpactedstoneinpatientwithacutepancreatits
ercp es for abp
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)

slide20

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

slide21

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

slide22

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

slide23

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

slide24

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

slide25

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
slide26

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)
slide27

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

slide28

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%)

slide29

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%)

slide30

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%)

slide31

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%)

slide33

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

slide34

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%)
slide35

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)

slide36

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)

slide37

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

slide38

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 %

slide40

ERCP / ES for ABP – Pooledanalysis

  • Designstotallydifferent
  • Differententrycriteria
  • Differenttreatmentregimens
  • Differentoutcomecriteria
slide41

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
slide42

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)

slide43

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
slide45

ERCP for ABP prognosis

No swelling

Minor swelling,limited to peripapillaryarea

Moderateswelling withextensive involvementof D2

Severe swellingwith extensiveinvolvementof D2, bluishdiscoloration

DGE MUSK

2000-2005

slide46

Duodenalswelling

DGE MUSK 2000-2005

slide47

Duodenalswelling

Normal duodenum

Deformed duodenal loop

D2 deformed and narrowed

DGE MUSK 2000-2005

slide48

Duodenalswelling

Edema of submucosal layer

DGE & DPAT

MUSK

2000-2005

Mucosal hyperemia

slide49

Duodenalswelling

Normal duodenum

Marked thickening of D2 wall

20 mm

DGE & DRAD MUSK, Helimed 2000-2005

slide50

Duodenalswelling

D2 swelling

limited to

antero-medial

wall

D2 swelling

limited to

peripapillary

area

DGE & DRAD MUSK, Helimed 2000-2005

slide51

Duodenalswelling

Severe swelling

with circular

D2 involvement;

lumen barely visible

in the most

severe cases

DGE & DRAD MUSK, Helimed 2000-2005

slide52

Duodenalswelling

Duodenopathy grade

n (851)%

% severe

% surgery

% mortality

SGS-10

N

69081%

31

4

2

3.9

MLD

405%

48

5

3

4.9

MOD

8810%

72

16

8

6.0

SEV

334%

94

42

36

7.9

p

0.0000

0.0000

0.0000

0.0000

Marek et al., Gut 2005 (abstract)

slide53

ERCP for ABP prognosis

  • Gastric stasis(I 9%; S 73%; RR=2.1)
  • Erosivegastropathy(I 9%; S 55%; RR=1.5)
  • Unident. / v. small papilla (I 5%; S 55%; RR=1.8)
  • Unident. / tight orifice (I 17%; S 54%; RR=1.5)
  • Failed initial CBD access(I 9%; S 61%; RR=1.7)
  • Small CBD Ø≤ 4 mm (I 5%; S 62%; RR=1.8)
  • Erosiveduodenopathy!!! (I 5%; S 31%; RR=0.7)

I = incidence

S = severe AP

slide54

ERCP for ABP prognosis – Ease of CBD cannulation

Easy

Normal

Difficult

Failed initial

p

n

308

203

266

74

Severe

%

30

39

41

61

0.000

Surgery %

3

5

10

14

0.001

Mortality

%

2

3

5

11

0.004

Marek et al., UEGW 2006

slide55

ERCP for ABP prognosis – CBD diameter

mm

0 ÷ 4

5 ÷ 8

9 ÷ 12

13 +

p

n

37

269

297

137

Severe

%

62

42

34

20

0.000

Surgery %

19

7

6

1

0.000

Mortality

%

11

4

2

1

0.021

Marek et al., UEGW 2006

slide56

ERCP for ABP prognosis

  • ERCP should not be done purely for prognostic assessment
  • ERCP should not replace current prognostic systems
  • When urgent ERCP is done for treatmentof acute episode of ABP,it may be of value to record findingscarrying possible prognostic information
prognosis of abp major duodenal papilla
Prognosis of ABPMajor duodenal papilla

Unident. to small

Normal

Large / v. large

W impacted stone

p

n

237

271

256

87

Severe

%

55

31

32

32

0.000

Surgery %

14

5

4

1

0.000

Mortality

%

10

2

3

0

0.000

Marek et al., UEGW 2006

pancreatic duodenopathy
Pancreatic duodenopathy

Duodenopathy grade

n (851)n CT (162)

Duodenum

Wall thick.(mm)

Diameter(mm)

Lumen(mm)

L/D(%)

N

69075

6.0

23.3

14.5

61

MLD

4023

6.8

24.7

14.5

57

MOD

8844

7.8

26.4

13.5

51

SEV

3320

9.4

26.0

9.0

35

p

0.0000

0.0029

0.0004

0.0000

Marek et al., Gut 2005 (abstract)

slide59

Duodenopathy grade

n (851)%

Age (y)

Sex(% F)

BMI (kg/m2)

SE failure(%)

N

69081%

57.2

73

28.9

4

MLD

405%

62.1

53

30.6

13

MOD

8810%

60.7

59

31.9

17

SEV

334%

65.1

49

32.3

70

p

0.0077

0.0001

0.0000

0.0000

Marek et al., Gut 2005 (abstract)

slide60

Duodenopathy grade

n (851)%

CRPmax48 mg/L

IL-6max48pg/mL

WBCmax48 G/L

AP-Ocum48(score)

CTSI72h(score)

N

69081%

123

120

10.5

9.6

1.7

MLD

405%

163

144

11.8

12.2

2.3

MOD

8810%

232

267

14.9

12.8

3.5

SEV

334%

299

259

14.6

18.8

4.9

p

0.0000

0.0000

0.0000

0.0000

0.0000

Marek et al., Gut 2005 (abstract)

slide61

Patients flow

1024

Acute pancreatitis

Non-biliary AP, late phase ABP

48

Early phase of ABP(within 48 h of pain)

976

18

No ERCP

Urgent ERCP

958

18% / 958

20% / 881

77

Failed ERC

8% / 958

Impacted stone

881

Successful ERC

92% / 958

385

CBD stones

172

43% / 881

496

No CBD stone(s)

56% / 881

239

Indications for ES w/o CBDS(jaundice, AOC, pregnancy, children, etc.)

No other indicationsfor ES

257

27% / 881

29% / 881

Stratification for gallbladder stones

RANDOMIZATION

4

CBD mini-stones

ITT

PP

101 GBS+

25 GBS-

105 GBS+

26 GBS-

CM

ES

ES

131

127

126