THE MANAGEMENT OF ACUTE PANCREATITIS
Professor Ravi KantMB, MS, FRCS (Edinburgh), FRCS (Glasgow), FACS, FICS,
DNB, FAIS, FAMS,
1
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. 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
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
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
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 (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 Consensus1992
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
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 0 points Grade 0.33 2 points Grade 0.5 4 points Grade > 0.5 6 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
Santorini1999
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
Local Phlegmon Abcess Pseudocyst Ascitis pseudoanurysm Adjacent organ
envolvment
Systemic pulmonary Cardiac Hematological GI Renal Metabolic CVS Fat necrosis
74
75
76
77
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
SEVERITY
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 N=50 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
92
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
Causes Acute or chronic pancreatitis
abdominal trauma.
Duct obstruction.
98
Presenting symptoms
Epigastric pain
Nausea
Vomiting
Weight loss
Mild Fever
Jaundice
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
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
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
Differential diagnosis:•Acute pancreatic fluid collections.•Serous cystadenoma of the pancreas•Mucinous cystadenoma of the pancreas•Mucinous cystadenocarcinoma•Pancreatic retention cyst
103
Investigations:
•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
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
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
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
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
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
MRMR 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
MRIA 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
Endoscopic Retrograde Cholangiopancreatography
(ERCP) is not necessary in diagnosing pseudocysts; however, it is useful in planning drainage strategy.
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
Complications Rupture
A controlled rupture into an enteric organ occasionally causes GI bleeding.
On rare occasions, a profound rupture into the peritoneal cavity causes peritonitis
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.
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
Management: If a pseudocyst is persistent over
many months or causing symptoms then treatment of the cyst is required.
119
External DrainageCatheter 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
Internal drainage:•The majority of patients who require treatment for their pseudocysts are treated by surgery.
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
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
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
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
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
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
Prognosis The failure rate for drainage
procedures is about 10%, the recurrence rate is about 15%, and the complication rate is 15-20%.
129