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

2. INTRODUCTION

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

5. DEFINITION

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

7. EPIDEMIOLOGY

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. Epidemiology
Local statistics?

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

11. PATHOPHYSIOLOGY

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

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

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

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. Pathophysiology

19. Pathophysiology

20. Pathophysiology

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

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

23. DIAGNOSIS

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

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

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

27. Cullen’s sign

28. Grey Turner’s sign

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. 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. Diagnosis Serum markers P/S – amylase Lipase
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

32. Diagnosis

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. RADIOLOGY (diagnostic)

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

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

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

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

39. PROGNOSIS

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

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

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

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

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

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. CT scan (prognostic aspect)

50. CT scan (prognostic aspect)

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. 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. CT scan (prognostic role)
Grade of necrosis and the points assigned per grade are as follows:
None points
Grade points
Grade points
Grade > points

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

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. 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. MANAGEMENT

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

59. MANAGEMENT OF MILD PANCREATITIS

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

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

62. Management (mild)

63. Management (mild)

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

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

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

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. 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. 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. 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. MANAGEMENT OF SEVERE PANCREATITIS

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

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

78. Pseudocyst

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

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 R I T Y

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

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

87. Specific considerations of biliary pancreatitis

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

91. Suggested algorithm

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. Your comments….

95. Pancreatic Psudocyst

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.  Acute or chronic pancreatitis
abdominal trauma.
Duct obstruction.

98. Epigastric pain
Nausea
Vomiting
Weight loss
Mild Fever
Jaundice

99. 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. 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. It moves very slightly with respiration.
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
101
101

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

103. Lab studies
Imaging studies
E.R.C.P

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

105. 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. 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. CT scan is the investigation of choice in pancreatic pseudocysts
CT scan is the investigation of choice in pancreatic pseudocysts. It has a sensitivity of % 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. 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. 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. 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. 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. (ERCP) is not necessary in diagnosing pseudocysts; however, it is useful in planning drainage strategy.

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. 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.
116
116

117. All cysts do not require treatment
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. If a pseudocyst is persistent over many months or causing symptoms then treatment of the cyst is required.

119. 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. 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. The majority of patients who require treatment for their pseudocysts are treated by surgery.

122. 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. Continue Cysto-gastrostomy Cysto-jejunostomy: Cysto-duodenostomy:
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. 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. 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. 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. 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. The failure rate for drainage procedures is about 10%, the recurrence rate is about 15%, and the complication rate is 15-20%.

129. Thank You