Ap

1. THE MANAGEMENT OF
ACUTE PANCREATITIS
Professor Ravi Kant
MB, MS, FRCS (Edinburgh), FRCS (Glasgow), FACS, FICS,
DNB, FAIS, FAMS,
1

2. 2
INTRODUCTION

3. 3
Introduction
 “In the growing world of EBM, only 30%
of surgery is based on evidence while
70% of medicine is evidence based” EJS,
Sep 2005

4. 4
Introduction
 Stress will be on Diagnosis, workup,
prognostic predictors and management
 Basic sciences

5. 5
DEFINITION

6. 6
Definition
 “Acute pancreatitis”:
 Inflammation of the pancreas without, or
with minimal fibrosis.

7. 7
EPIDEMIOLOGY

8. 8
Epidemiology
 300,000 annually in US
 10-20% are severe
 Total annual cost of 2 billion $$$
 (Biliary + alcoholic) 90%
 Even in the west, biliary pancreatitis is
the most prevalent type.
 Incidence among AIDS patients 4-22%

9. 9
Epidemiology
 Local statistics?

10. 10
Epidemiology
 “Profile of acute pancreatitis in Jizan,
Saudi Arabia” Saudi Med J. 2003 Jan;24(1):72-5.
 (KFCH), Jizan, KSA over 12 years regional
 42% (biliary), 18% Post ERCP
 “Pattern of acute pancreatitis” Saudi Med J.
2001 Mar;22(3):215-8.
 Cross sectional, 2 years, Asir central
hospital
 68% found to be biliary

11. 11
PATHOPHYSIOLOGY

12. 12
Pathophysiology
 Causes
 Biliary tract disease
 Alcohol
 Hyperlipedemia
 Hypercalcemia
 Trauma
 ERCP
 Ischemia
 Pancreatic neoplasia
 Pancreas divisum
 Ampullary lesions
 Duodenal lesions
 Infections
 Venom
 Drugs
 idiopathic

13. 13
Pathophysiology
 Theories behind mechanism of biliary
pancreatitis
 Common channel theory
 Incompetent sphincter theory
 Co-localization theory

14. 14
PATHOPHYSIOLOGY
 Common channel theory
 “Opie 1901”
 Detergent effect of bile

15. 15
Pathophysiology
 Critique of common channel theory
 Higher hydrostatic pressure in PD
 Introduction of bile into PD in animal
models failed to cause AP

16. 16
Pathophysiology
 Incompetent sphincter theory
 Incompetent sphincter of Oddi due to stone
passage  reflux  AP
 Critique
 How come papillotomy doesn’t routinely cause
AP??

17. 17
Pathophysiology
 Co-localization theory “Steer & Saluja”
1998
 Most acceptable
 Stones  PD ductal hypertension 
ducutle rupture
 Ductal pH = 9 …… parynchemal pH = 7
 trypsinogen + cathepsin B  trypsin 
autodigestion cascade

18. 18
Pathophysiology

19. 19
Pathophysiology

20. 20
Pathophysiology

21. 21
Pathophysiology
 Support of co-localization theory
 CA-074me (cathepsin B inhibitor)
prevented AP in 2 different models of acute
pancreatitis

22. 22
Pathophysiology
 Alcoholic pancreatitis
 No such thing as acute alcoholic
pancreatitis
 It is actually the first attack of chronic
alcoholic pancreatitis

23. 23
DIAGNOSIS

24. 24
Diagnosis
 Clinical picture
 Investigations
 “Acute pancreatitis is a diagnosis of
exclusion” Schwartz’s

25. 25
Diagnosis
 Hx:
 Epigastric pain
 Radiating to back
 Nausea, vomitting
 Precipitating factor?

26. 26
Diagnosis
 Physical
 V/S  variable
 Epigastric tenderness
 Cullen’s / Grey Turner’s (1%)
 Findings of complication(s)

27. 27
Cullen’s sign

28. 28
Grey Turner’s sign

29. 29
Diagnosis
 Serum markers
 Amylase
 Easiest to measure and most widely used
 Rises immediately
 Peaks in few hours
 Remains for 3-5 days
 “Three fold rise is diagnostic”
 May be normal in severe attacks
 May be falsely negative in hyperlipedimic patients
 Inverse correlation between severity and serum amylase
level
 No need to repeat

30. 30
Diagnosis
 Serum markers
 Urine amylase
 Remains elevated for a few more days
 Increase excretion of amylase with attacks of
AP
 Of great value when dealing with severe
pancreatitis

31. 31
 Serum markers
 P/S – amylase
 P amylase increases specificity to 93%
 Lipase
 “the serum marker of highest probability of
disease”
 Specificity of 96%
 Remains elevated for longer time than total
amylase
Diagnosis

32. 32
Diagnosis

33. 33
Causes of hyperamylesemia
 Pancreatitis p
 Choledocolethiasis p
 Parotitis s
 Renal failure s/p
 Liver cirrhosis s/p
 perforated bowel p
 mesenteric infarction p
 intestinal obstruction p
 Appendicitis p
 Peritonitis. P
 Gyne disease s
 Malignancies
 Lung CA
 Ovarian CA
pancreatic CA
 Colonic CA
 pheochromocytoma;
 Thymoma
 multiple myeloma
 breast cancer

34. 34
RADIOLOGY (diagnostic)

35. 35
Radiology
 Diagnostic role
 X-ray
 U/S
 CE-CT

36. 36
Radiology
 X-ray
 Air in the duodenal C loop
 Sentinel loop sign
 Colon cutoff sign
 All these signs are non specific

37. 37
Radiology
 CE-CT
 Enlargement of the pancreas
 (focal/diffuse)
 Irregular enhancement
 Shaggy Pancreatic contour
 Thickening of fascial planes
 fluid collections.
 Intraperitoneal / retroperitoneal
 Retroperitoneal air

38. 38
Radiology
 U/S
 Diagnosis of gallstones
 F/U of pseudocysts.
 Dx pseudoaneurysms
 EAUS vs. EUS

39. 39
PROGNOSIS

40. 40
Prognosis
 Course either mild or severe
 Mild = edematous pancreatitis
 Severe = necrotic pancreatitis
 No such thing as moderate pancreatitis

41. 41
Prognosis
 Serum markers
 CT
 Systemic complications
 Prognostic scores
 Ranson
 Apache II
 Modified Glasgow
 Atlanta
Atlanta Consensus
1992

42. 42
Prognostic scores
 Ranson’s
 Published in 1974
 Predictor of morbidity/mortality
 <2 0% mortality
 3-5 10-20%
 >7 >50% mortality
 Critique of Ranson’s
 11 parameters
 48 hours
 No predictor value beyond 48hrs
 Too pessimistic for today’s healthcare system

43. 43

44. 44
Prognostic scores
 APACHE II
 Immediate
 Acute and chronic parameters
 Complicated
 >7 = severe pancreatitis

45. 45
Prognostic biochemical
markers
 Biochemical markers of prognosis
 Ideally
 High sensitivity
 High specificity
 Discriminate severe from mild
 Immediate
 Widely available
 Amylase & lipase
 Highly sens./spec.
 Lack prognostic value

46. 46
Prognostic biochemical
markers
 Alternatives
 CRP
 2 macroglobulin
 PMN elastase
 1 antitrypsin
 Phospholipase A2
 “CRP seems to be the marker of choice in
these settings”
 CRP >150 is diagnostic of severe
pancreatitis

47. 47
Prognostic biochemical
markers
 Other markers
 IL-6
 Urinary TAP
 These showed great promise in models
and clinical trials
 Failed in larger scale trials

48. 48
CT scan (prognostic aspect)
 “CT scanning with bolus IV contrast has
become the gold standard for detecting and
assessing the severity of pancreatitis”
 “Currently, IV bolus contrast enhanced CT
scanning is routinely performed on patients
who are suspected of harboring severe
pancreatitis, regardless of their Ranson’s or
APACHE scores” Schwartz’s

49. 49
CT scan (prognostic aspect)

50. 50
CT scan (prognostic aspect)

51. 51
CT scan (prognostic role)
 Balthazar CT-severity index (CTSI)
 CTSI considers degree of necrosis
 Also considers the CT grade
 A final score is given and correlates with
mortality and complication development

52. 52
CT scan (prognostic role)
 Balthazar grading
 Grade A - Normal-appearing pancreas 0
 Grade B - Enlargement of the pancreas 1
 Grade C - Pancreatic gland abnormalities a with
peripancreatic fat infiltration 2
 Grade D - A single fluid collection 3
 Grade E - Two or more fluid collections 4

53. 53
CT scan (prognostic role)
 Grade of necrosis and the points
assigned per grade are as follows:
 None 0 points
 Grade 0.33 2 points
 Grade 0.5 4 points
 Grade > 0.5 6 points

54. 54
CT scan (prognostic role)
 Overall prognostic outlook:
CTSI Mortality Complication
0-3 3% 8%
4-6 6% 35%
7-10 17% 92%

55. 55
Is CT superior???
 “Computed Tomography Severity Index,
APACHE II Score, and Serum CRP
Concentration for Predicting the
Severity of Acute Pancreatitis”*
 n=55
 CTSI,APACHE and CRP had p <0.01

56. 56
Prognosis
 Recommendation for assessing
severity:
 Mild is defined as:
 No systemic complications
 Low APACHE/Ranson scores
 CE-CT findings (Balthazar)
 CRP level <150
Santorini
1999

57. 57
MANAGEMENT

58. 58
MANAGEMENT
 Management depends on severity
 We will consider management of
edematous pancreatitis separately from
necrotizing pancreatitis for purpose of
simplification

59. 59
MANAGEMENT OF MILD
PANCREATITIS

60. 60
Management (mild)
 Core of treatment based on
 Physiological monitoring
 Metabolic support
 Maintenance of fluids and electrolytes

61. 61
Management (mild)
 NG suction
 H2 blockers
 Gastric acid reaching the duodenum will
activate pancreatic secretion???
 Large studies failed to show any benefit

62. 62
Management (mild)

63. 63
Management (mild)

64. 64
Management (mild)
 What is the role of anti-secretory
agents?
 Atropin
 Calcitonin
 Somatostatin
 Glucagon
 Flurouracil
 Unproven benefit*

65. 65
Management (mild)
 Pancreatitis is an autodigestive process
 Role of protease inhibitors?
 Aprotinin
 Gabexate mesylate
 Camostate
 Phospholipase A2 inhibitors
 FFP
 No benefit

66. 66
Management (mild)
 Pancreatitis is an inflamatory process
 Role of anti-inflamatory drugs?
 Indomethacin
 Prostaglandin inhibitors
 Interleukin-10
 No measurable benefit

67. 67
Management (mild)
 Vascular injury is mediated by platelet
aggregating factor
 What’s the role of PAF inhibitors?
 PAF acetylhydrolase
 Lexipafant
 Great results in models
 Great results in small clinical trials
 Failed in larger studies
 Verdict: useless

68. 68
Management (mild)
 Question to audience:
 When dealing with acute pancreatitis,
do u start Abx therapy? (hands please)
 “Antibiotic therapy has not proved to be
of value in the absence of signs or
documented sources of infection”

69. 69
Management (mild)
 Mainstay of management is supportive
 NPO
 IVF
 When to resume oral intake?
 Absence of pain
 Absence of tenderness
 Patient feeling hungry
 On average takes about 3-7 days
 Sips of water and build up to low protein low
fat diet

70. 70
Management (mild)
 Any drug therapy for acute pancreatitis?
 “None of the evaluated medical treatments
is recommended (level A)”*
 Meta-analysis considering gabexate
mesylate, octreiotide, aprotinin and
lexipafant

71. 71
MANAGEMENT OF SEVERE
PANCREATITIS

72. 72
Management (severe)
 Severe pancreatitis:
 > Ranson / APACHE
 CRP >150
 Systemic complications
 Necrosis on CE-CT
 Hemodynamic compromise

73. 73
Management (severe)
 Complications
 Local
 Phlegmon
 Abcess
 Pseudocyst
 Ascitis
 pseudoanurysm
 Adjacent organ
envolvment
 Systemic
 pulmonary
 Cardiac
 Hematological
 GI
 Renal
 Metabolic
 CVS
 Fat necrosis

74. 74

75. 75

76. 76

77. 77

78. 78
Pseudocyst

79. 79
Management (severe)
 Sterile necrosis
 Absence of retroperitoneal air on CT
 Prognosis
 0% mortality without complications
 38% with single sys. complication

80. 80
Management (severe)
 How to approach sterile necrosis?:
 No sys. Comp., no infec. (i.e. uncomplicated)
 supportive
 Sys. Comp. + infection? ( mild complication)
 CT guided aspiration  gram stain/culture  Abx
 Mult. Sys comp + toxicity/shock (frank complication)
 surgical debridment
S
E
V
E
R
I
T
Y

81. 81
Management (severe)
 Role of prophylactic Abx?
 Previously thought to have no role in sterile necrosis
 Prophylaxis indicated whenever there is necrosis
 Drugs with proven benefit
 Imipenem
 Flagyl
 3rd gen. Cephalosporins
 Abx prophylaxis reduced:*
 Sepsis by 21.1%
 Mortality by 12.3%

82. 82
Management (severe)
 Role of Antifungal medication
 Candida is a common inhabitant of upper
GI tract
 Risk of secondary infection
 Empiric fluconazole?
 Clansy TE “current management of necrotizing
pancreatitis”*

83. 83
Management (severe)
 Nutritional support
 NPO with resumption of diet when fit
 If NPO > 7 days…
 TPN vs. Jujenal tube feeding?
 TPN: gastric mucosal atrophy  bacterial translocation
 Jujenal tube feeding: induces pancreatic secretion
 Inconclusive studies:
 Jujenal T. feeding is superior*

84. 84
Management (severe)
 Benefit of enteral feeding
 Prospective randomized trial
 n=34
 Severe acute pancreatitis
 “enteral feeding modulates the inflamatory
and sepsis response in acute pancreatitis”*

85. 85
Management (severe)
 NG vs. NJ feeding
 Prospective randomized trial
 N=50
 Mortality as endpoint
 No statistically significant benefit of NJ*
NG mortality NJ mortality
18.5% 31.8%

86. 86
Management (severe)
 Something very important has been
missing in the presentation…
 Where is pain management?
 Also missing from the research scene

87. 87
Specific considerations of
biliary pancreatitis

88. 88
Management (severe)
 Specific consideration of biliary
pancreatitis:
 Majority of stones will pass within hours
 Some might impact
 Patient at risk of subsequent stone obst.
 NECROSECTOMY

89. 89
Management (severe)
 If hyperbili is dropping:
 Lap chole with surgical duct clearance
 <72 hours vs. >72 (within admission)
 If patient critical  ERCP stone clearance
 Routine ERCP NOT ADVOCATED

90. 90
Management (severe)
 If hyper bili persists:
 confirm presence of stone before ERCP
(MRCP, EUS)

91. 91
Suggested algorithm

92. 92

93. 93
Conclusion
 Acute pancreatitis is a hot area for
research
 Advances at the cellular level show
promise to “halt”pancreatitis
 Most patients need just supportive care
 No indication for Antibiotics in mild type
 Severe pancreatitis needs antibiotics
 Surgical management ►gallstones /
complications

94. 94
Your comments….

95. 95
Pancreatic Psudocyst

96. 96
Definition:
Pseudocysts are
encapsulated localized
collection of pancreatic
enzyme, inflammatory fluid
and necrotic debris on
pancreas or in part or the
whole of the lesser sac.
They are distinguished
from other types of
pancreatic cysts by their
lack of an epithelial lining.

97. 97
Causes
 Acute or chronic pancreatitis
 abdominal trauma.
 Duct obstruction.

98. 98
Presenting symptoms
Epigastric
pain
Nausea
Vomiting
Weight loss
Mild Fever
Jaundice

99. 99
Physical Examination
•The sensitivity of physical
examination findings is limited.
•Tender abdomen.
•Palpable mass in the abdomen
with an indistinct lower edge.
•The upper limit is not palpable .

100. 100
Physical Examination
•The sensitivity of physical examination findings
is limited.
•tender abdomen.
•palpable mass in the abdomen with an
indistinct lower edge.
•The upper limit is not palpable .

101. 101
Physical Examination
•Its usually resonant to percussion because it is
covered by the stomach.
•It moves very slightly with respiration.
•it is not possible to elicit fluctuation or a fluid
thrill.
•Peritoneal signs suggest rupture of the cyst or
infection

102. 102
Differentialdiagnosis:
•Acute pancreatic fluid collections.
•Serous cystadenoma of the
pancreas
•Mucinous cystadenoma of the
pancreas
•Mucinous cystadenocarcinoma
•Pancreatic retention cyst

103. 103
Investigations:
•Lab studies
•Imaging
studies
• E.R.C.P

104. 104
Serum tests:
 Amylase and lipase levels are often elevated
but may be normal
 BilirubinandLFT findings may be elevated if
the biliary tree is involved.

105. 105
Lab Studies
 Analysis of the cyst fluid may help
differentiate pseudocysts from
tumors.
 Attempt to exclude tumors in any
patient who does not have a clear
history of pancreatitis.

106. 106
Analysis of cyst fluid
 Carcinoembryonic antigen (CEA) and
carcinoembryonic antigen-125 (CEA-125)
tumor marker levels are low in pseudocysts
and elevated in tumors.
 Fluid viscosity is low in pseudocysts and
elevated in tumors.
 Amylase levels are usually high in
pseudocysts and low in tumors.
 Cytology is occasionally helpful in diagnosing
tumors, but a negative result does not exclude
tumors.

107. 107
Abdominal CT scan
 CT scan is the investigation of
choice in pancreatic pseudocysts.
It has a sensitivity of 90-100% and
is not operator dependent.
 The usual finding on CT scan is a
large cyst cavity in and around the
pancreas.
 Multiple cysts may be present.

108. 108
Abdominal CT scan
 The pancreas may appear irregular or
have calcifications.
 Pseudoaneurysms of the splenic artery,
bleeding into a pseudocyst, biliary and
enteric obstruction, and other
complications may be noted on CT
scan.
 The CT scan provides a very good
appreciation of the wall thickness of the
pseudocyst, which is useful in planning
therapy.

109. 109
Abdominal ultrasound:
While cystic fluid collections in and
around the pancreas may be
visualized via ultrasound,
the technique is limited by operator
skill, the patient's habitus, and
overlying bowel gas.
As such, ultrasound is not the study of
choice for diagnosis.

110. 110
MR
MR is not necessary
for the diagnosis of
pseudocysts; however,
it is useful in detecting
a solid component to
the cyst and in
differentiating between
organized necrosis and
a pseudocyst.

111. 111
MRI
A solid component
makes catheter
drainage difficult;
therefore, in the setting
of acute necrotizing
pancreatitis with
resultant pseudocyst,
an MRI may be very
important before a
planned catheter
drainage procedure.

112. 112
Endoscopic Retrograde
Cholangiopancreatography
(ERCP) is not necessary in
diagnosing pseudocysts;
however, it is useful in
planning drainage strategy.

113. 113
Complications
 Infection of the pseudocyst
patients develop fever or an elevated WBC count.
Treat infection with antibiotics and urgent
drainage .
 Gastric outlet obstruction, manifesting as nausea and
vomiting, is an indication for drainage .

114. 114
Complications
 Rupture
 A controlled rupture into an enteric organ
occasionally causes GIbleeding.
 On rare occasions, a profound rupture into the
peritoneal cavity causes peritonitis

115. 115
Continue
Bleeding
 is the most feared complication and
is caused by the erosion of the
pseudocyst into a vessel.
 Consider the possibility of bleeding in
any patient who has a sudden increase
in abdominal pain coupled with a drop
in hematocrit level or a change in vital
signs.

116. 116
Continue
Bleeding
 is the most feared complication and
is caused by the erosion of the
pseudocyst into a vessel.
 Therapy is emergent surgery or
angiography with embolization of the
bleeding vessel.

117. 117
Management: 4X4, 5X5,6X6
 All cysts do not require treatment. In
many cases the pseudocysts may
improve and go away on their own.
 In a patient with a small (less than
5cm) cyst that is not causing any
symptoms, careful observation of the
cyst with periodic CT scans is
indicated.

118. 118
Management:
 If a pseudocyst is persistent over
many months or causing symptoms
then treatment of the cyst is
required.

119. 119
External Drainage
Catheter drainage:
•Percutaneous catheter
drainage is the procedure of
choice for treating infected
pseudocysts,
• allowing for rapid drainage
of the cyst and identification
of any microbial organism.
A high recurrence and failure
rate exist.

120. 120
Continue
 Percutaneous catheter drainage is
contraindicated in patients who are
poorly compliant and cannot manage
a catheter at home.
 It is also contraindicated in patients
with strictures of the main pancreatic
duct and in patients with cysts
containing bloody or solid material.

121. 121
Internal drainage:
•The majority of patients who
require treatment for their
pseudocysts are treated by
surgery.

122. 122
Internal drainage:
In the surgical procedure a
connection is created between
the cyst and an adjacent
intestinal organ to which the cyst
is adherent to such as the
stomach. This connection allows
the cyst to drain into the
stomach.

123. 123
Continue
 Cysto-gastrostomy
a connection is created between the back wall of the
stomach and the cyst , the cyst drains into the
stomach.
 Cysto-jejunostomy:
a connection is created between the cyst and the
small intestine.
 Cysto-duodenostomy:
a connection is created between the duodenum and
the cyst.
 During surgical drainage procedure biopsy of
cyst wall must be done to rule out a cystic
carcinoma.

124. 124
Endoscopic technique
 In this procedure a gastroenterologist
drains the pseudocyst through the
stomach by creating a small opening
between the cyst and the stomach during
endoscopy.

125. 125
Endoscopic technique
 In selected patients this treatment can
successfully treat pseudocyst.
 The disadvantage of this technique is that
if there is dead tissue in the pseudocyst
cavity or if the cyst is very large then
infection or recurrence of pseudocyst with
this technique may occur.

126. 126
Insertion of a pancreatic stent:
In this technique the gastroenterologist
may insert a drain into the cyst during an
ERCP.
If the drain is placed directly into the cyst
then the fluid from the cyst is drained
into the intestine through this tube.

127. 127
Prognosis
 Most pseudocysts resolve without
interference, and patients do well
without intervention.
 Outcome is much worse for patients
who develop complications or who
have the cyst drained.

128. 128
Prognosis
 The failure rate for drainage
procedures is about 10%, the
recurrence rate is about 15%, and the
complication rate is 15-20%.

129. 129