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GENERAL SURGERY BOARD REVIEW MANUAL
STATEMENT OF
EDITORIAL PURPOSE
The Hospital Physician General Surgery Board
Review Manual is a peer-reviewed study guide
for residents and practicing physicians preparing for board examinations in general surgery.
Each quarterly manual reviews a topic essential to the current practice of general surgery.
PUBLISHING STAFF
PRESIDENT, GROUP PUBLISHER
Bruce M. White
EDITORIAL DIRECTOR
Debra Dreger
SENIOR EDITOR
Becky Krumm
ASSISTANT EDITOR
Rita E. Gould
EXECUTIVE VICE PRESIDENT
Barbara T. White
Contemporary Treatment
of Acute Pancreatitis
Series Editor: Kamal M.F. Itani, MD, FACS
Chief of Surgery, Boston VA Health Care System; Professor of Surgery,
Boston University; Associate Chief of Surgery, Boston Medical Center
and The Brigham and Women’s Hospital; Boston, MA
Contributors:
Scott F. Gallagher, MD
Assistant Professor, Department of Surgery, University of South
Florida, Tampa, FL
Michel M. Murr, MD, FACS
Associate Professor, Department of Surgery, University of South
Florida, Tampa, FL
EXECUTIVE DIRECTOR
OF OPERATIONS
Jean M. Gaul
PRODUCTION DIRECTOR
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ADVERTISING/PROJECT MANAGER
Table of Contents
Patricia Payne Castle
Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2
SALES & MARKETING MANAGER
Case 1 . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2
Deborah D. Chavis
Case 2 . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 5
Case 3 . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 8
NOTE FROM THE PUBLISHER:
This publication has been developed without
involvement of or review by the American
Board of Surgery.
Endorsed by the
Association for Hospital
Medical Education
Case 4 . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 10
Summary Points . . . . . . . . . . . . . . . . . . . . . . . . . . . 11
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 11
Cover Illustration by Joe Wilder, MD
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General Surgery Volume 8, Part 1 1
GENERAL SURGERY BOARD REVIEW MANUAL
Contemporary Treatment of
Acute Pancreatitis
Scott F. Gallagher, MD, and Michel M. Murr, MD, FACS
INTRODUCTION
Acute pancreatitis is an inflammatory disease of the
pancreas that can progress into a systemic inflammatory state with resultant multi-organ dysfunction. It is estimated that most of the 250,000 individuals diagnosed
with acute pancreatitis each year in the United States
develop pancreatitis secondary to gallstones or alcohol
intake. Most episodes of acute pancreatitis are mild and
resolve with minimal specific interventions; however,
approximately 2% to 5% of patients develop severe
pancreatitis associated with pancreatic necrosis and may
require operative intervention.1 The precipitating factor induces acinar cell injury resulting from colocalization of zymogen granules and lysozymes. This localized
inflammation in the pancreas can propagate systemically as pancreatic enzymes induce cytokine production
in the pancreas and affected organs, such as the lungs,
liver, and kidneys. Despite advancements in our understanding of the pathophysiology of acute pancreatitis,
the mainstay of treatment remains nonoperative, except in patients with necrotizing pancreatitis. Multiple
clinical trials utilizing anticytokine agents have failed to
reduce mortality.2,3 This monograph uses hypothetical
cases to review the evaluation and management of
acute pancreatitis.
NOMENCLATURE
In response to confusion in nomenclature, a clinically based classification system has been adopted by
many experts worldwide and will be used throughout
this text4:
Mild acute pancreatitis. An acute inflammation of
the pancreas with minimal distant organ dysfunction
and an uneventful recovery.
Severe acute pancreatitis. An acute inflammation of
the pancreas associated with organ failure and/or local
complications such as necrosis, abscess, or pseudocyst.
Acute fluid collection. Acute fluid collections occur
early in the course of acute pancreatitis, are located in
or near the pancreas, and always lack a wall of granula-
2 Hospital Physician Board Review Manual
tion or fibrous tissue. This is the most misunderstood
term and is commonly confused with a pseudocyst.
Pancreatic necrosis. Diffuse or focal areas of nonviable pancreatic parenchyma, which are typically associated with peripancreatic fat necrosis.
Acute pseudocyst. A collection of pancreatic fluid
enclosed by a wall of fibrous or granulation tissue that
arises as a consequence of acute pancreatitis, chronic
pancreatitis, or trauma to the pancreas.
Pancreatic abscess is a collection of pus, usually in
proximity to the pancreas, containing little or no pancreatic necrosis, which arises as a consequence of acute
pancreatitis or trauma to the pancreas.
CASE 1
PATIENT PRESENTATION
Patient 1 is a 42-year-old man who is admitted to the
hospital with acute onset of abdominal pain, nausea,
and vomiting. He has epigastric tenderness but no peritoneal signs. Admission laboratory test results are:
hemoglobin, 16.2 mg/dL; leukocyte count, 18 ×
103/mm3; serum creatinine, 1.3 mg/dL; total bilirubin,
1.8 mg/dL; amylase, 432 U/L; lipase, 242 U/L; and
alkaline phosphatase level, 260 U/L.
• What is an appropriate diagnostic plan for this patient?
DISCUSSION
This patient’s clinical presentation is consistent with
acute pancreatitis. Other abdominal conditions that
mimic acute pancreatitis can be ruled out by history,
physical examination, and laboratory data; however,
imaging modalities should be used to confirm the diagnosis of acute pancreatitis.
Clinical Presentation
The cardinal clinical symptom of acute pancreatitis is
constant epigastric pain of insidious onset, often radiating
to the back. Other clinical findings include anorexia,
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C o n t e m p o r a r y Tr e a t m e n t o f A c u t e P a n c r e a t i t i s
Table 1. Clinical Findings in Patients with Acute
Pancreatitis
Table 2. Biochemical Profile of Patients with Acute
Pancreatitis
Symptom
Hemoconcentration
Abdominal pain
Anorexia
Incidence (%)
085–100
85
Leukocytosis
Azotemia and increased creatinine
Hyperbilirubinemia
Nausea and vomiting
50–90
Ileus
50–80
Increased AST/ALT and γGT
Fever
10–80
Increased alkaline phosphatase
Abdominal mass
05–20
Hyperglycemia
Hyperlipidemia/hypertriglyceridemia
Data from Murr MM, Norman J. Acute pancreatitis. In: Greenfield LJ,
Mulholland MW, Oldham KT, et al, editors. Surgery: scientific principles and practice. 3rd ed. Philadelphia: Lippincott Williams & Wilkins;
2001:867.
Hypercalcemia
Hypomagnesemia
Hypoxemia
Acidosis/alkalosis
fever, nausea, vomiting, ileus, and abdominal distention
(Table 1). The spectrum of clinical presentation depends
on the severity of the disease process. Patients with
severe necrotizing pancreatitis can present with jaundice, hypotension, and signs of retroperitoneal hemorrhage, producing blue discoloration of the flanks (Grey
Turner sign), the umbilicus (Cullen sign), or the inguinal ligament (Fox sign). The differential diagnosis
includes gastritis, peptic ulcer disease, acute cholecystitis, pyelonephritis, intestinal ischemia, intestinal obstruction, intestinal perforation, and hepatitis.
Laboratory Tests
No single laboratory test or physical finding is pathognomonic for pancreatitis. Hyperamylasemia in a patient
with clinical signs and symptoms of acute pancreatitis is
the usual means of confirming the diagnosis of acute
pancreatitis.5 The degree of hyperamylasemia does not
correlate with disease severity, perhaps because of the relatively rapid clearance of amylase from plasma (amylase
half-life, 130 min). Clinical conditions associated with
hyperamylasemia of nonpancreatic origin include the
following: salivary gland injury, burns, head or multiple
trauma, diabetic ketoacidosis, macroamylasemia, renal
transplantation, renal dysfunction and hydronephrosis,
pneumonia, pregnancy, fallopian tube pathology, afferent loop syndrome, acute appendicitis, dissecting aortic
aneurysm, small bowel injury, perforated ulcer, small
bowel obstruction, and mesenteric ischemia.
Fractionation of plasma isoenzyme levels can be
used to differentiate pancreatic from salivary amylase.
Amylase is cleared by the kidneys; therefore, renal dysfunction can result in hyperamylasemia. In such a patient, determination of the ratio of amylase to creatinine clearance is potentially useful. This fractional
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Consumption coagulopathy
ALT = alanine aminotransferase; AST = aspartate aminotransferase;
γGT = gamma glutamyltransferase.
excretion of amylase (FeA) can be calculated using the
following formula:
FeA = (UA × SCr / UCr × SA) × 10
where S = serum and U = urine.
Clearance in excess of 4.5% to 6% is considered
abnormal but is not specific for acute pancreatitis. However, clinical findings or abdominal computed tomography (CT) scans have made these laboratory tests unnecessary in most instances.
Although the specificity of serum lipase is high
(> 95%), its sensitivity is lower (85%); therefore, serum
lipase determinations have not been found to be more
clinically useful than serum levels of amylase. Both tests
cost about the same. Nevertheless, concomitant increases in serum amylase and lipase have a 90% to 95% sensitivity and specificity in detecting acute pancreatitis in
patients with acute abdominal pain.5,6 Other enzymes
and products of acinar cell injury—such as trypsin, chymotrypsin, elastase, and phospholipase—have not been
shown to have any additional benefit to serum amylase
levels. Other biochemical features of acute pancreatitis
are listed in Table 2.
Diagnostic Imaging
Plain abdominal radiographs that demonstrate a sentinel loop, pancreatic calcifications, or an obscured
psoas muscle margin are not specific for acute pancreatitis. Ultrasonography is a rapid, inexpensive, and noninvasive tool for evaluating patients with presumed mild
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C o n t e m p o r a r y Tr e a t m e n t o f A c u t e P a n c r e a t i t i s
Table 3. Etiology of Acute Pancreatitis
Biliary tract stones
patients with recurrent “idiopathic” or complicated
pancreatitis; hence, it is indicated in these patients once
the acute phase of the disease has resolved.
Alcohol abuse
Postprocedural (ERCP/postoperative)
Trauma
Hyperlipidemia
Hyperparathyroidism/hypercalcemia
Medications
Infections
Tumors
Pancreas divisum
Pregnancy
Penetrating duodenal ulcer
Parasites
Hereditary
Idiopathic
ERCP = endoscopic retrograde cholangiopancreatography.
pancreatitis by assessing for edema of the pancreas and
by furnishing information on the status of the gallbladder and biliary ductal system. Ultrasonography is operator dependent and its utility is limited by dilated bowel
loops as well as its inability to detect parenchymal necrosis. The most common use for ultrasound in the clinical
setting of pancreatitis is to examine the biliary ductal system for the presence of dilated ducts or gallstones.
Contrast-enhanced dynamic CT has become the
standard and most widely used test to evaluate patients
with acute pancreatitis.7–9 CT is more sensitive than
ultrasonography for detecting parenchymal changes but
less sensitive for detection of cholelithiasis and choledocholithiasis. Findings on CT indicative of pancreatitis
include edema of the pancreas, peripancreatic fluid collections, as well as edema of the surrounding viscera and
mesentery. Absence of enhancement of the pancreatic
parenchyma by intravenous contrast signifies pancreatic
necrosis. Extravisceral gas is pathognomonic of infection
but is a rare finding. CT-based severity staging for acute
pancreatitis is as follows: (A) normal, (B) pancreatic
swelling, (C) peripancreatic fat abnormalities, (D) single fluid collection, and (E) multiple fluid collections.8,10
Endoscopic retrograde cholangiopancreatography
(ERCP), magnetic resonance imaging, and cholangiopancreatography serve little purpose, if any, as diagnostic modalities in acute uncomplicated pancreatitis.
ERCP can provide useful anatomic information about
4 Hospital Physician Board Review Manual
CASE 1 CONTINUED
Ultrasonography in the case patient, who has a history of mild alcohol intake, demonstrates multiple
small gallstones but no dilatation of the bile ducts.
• What is the most likely etiology of pancreatitis in
this patient?
DISCUSSION
Many patients develop acute pancreatitis because of
biliary tract stone disease or long-term ethanol abuse
(Table 3). Alcohol intake increases pancreatic fluid,
protein secretion, and the resistance of the ampulla.
The subsequent proteinaceous precipitates and plugs
induce pancreatic ductal hypertension and pancreatitis. With biliary tract stones, choledocholithiasis can be
demonstrated in 20% of patients with pancreatitis; however, only 2% of patients present with an impacted
stone in the ampulla. Nevertheless, gallstones are found
in the stools of 90% of patients with acute pancreatitis.1
These are important considerations because therapeutic interventions, such as ERCP, are necessary to extract
an impacted stone in only a few patients.
Postprocedural Complications and Trauma
Direct manipulation or retraction of the pancreas
appears to be the most common cause of postprocedural pancreatitis (gastric resection, 1%; common bile
duct exploration, 3%). Acute pancreatitis develops in
about 5% of patients after ERCP as well as several other
procedures remote from the pancreas.11 Hyperamylasemia is common after major trauma; however, the
full clinical picture of pancreatitis occurs in less than
5% of patients who sustain major blunt abdominal trauma.12
Hyperlipidemia, Hyperparathyroidism, and
Hypercalcemia
Acinar cell injury is thought to result from the liberation of free fatty acids from circulating triglycerides by
local action of lipases within pancreatic microcirculation. Hyperlipidemias may be the etiologic factor in
patients with recurrent and previously “idiopathic” pancreatitis. Hyperthyroidism increases calcium, a known
secretagogue that may cause pancreatitis because of calcium precipitation in the pancreatic duct; however, the
exact mechanism is unknown.
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C o n t e m p o r a r y Tr e a t m e n t o f A c u t e P a n c r e a t i t i s
Infections and Medications
Bacterial, fungal, and viral infections sometimes cause
pancreatitis. The recent epidemic of AIDS has uncovered
many cases of pancreatitis, most commonly caused by
cytomegalovirus infection and medications such as pentamidine. More than 85 drugs are suspected of causing
acute pancreatitis, but a clear and defined association has
been found with only a few,1 such as glucocorticoids,
furosemide, thiazides, warfarin, cimetidine, quinidine,
azathioprine, and clonidine. The mechanisms of druginduced pancreatitis are largely elusive and likely involve
different pathways.
Table 4. Ranson’s Criteria for Predicting the Severity
of Acute Pancreatitis*
Other Causes of Acute Pancreatitis
Other causes of acute pancreatitis include tumors,
pancreas divisum, pregnancy, and idiopathic causes. Of
patients with periampullary tumors, 1% to 3% present
with acute pancreatitis because the pancreatic duct is
obstructed. The association between pancreas divisum
and acute pancreatitis, however, is not absolute because
most individuals with pancreas divisum are asymptomatic and never develop pancreatitis. Acute pancreatitis also has been linked to pregnancy with an incidence
of 0.01% to 0.1%, but it is unclear whether pregnancy
is an independent risk factor. Finally, acute pancreatitis
develops in the absence of ductal obstruction or any
other identifiable cause in 10% of patients. Recent
large clinical trials have shown that an etiology can be
identified in most patients with idiopathic pancreatitis if
thorough diagnostic testing is undertaken.1
Within 48 hr
CASE 1 FOLLOW-UP
The patient undergoes an uneventful laparoscopic
cholecystectomy after resolution of acute pancreatitis.
The patient is symptom-free after the procedure.
CASE 2
PATIENT PRESENTATION
Patient 2 is a 47-year-old woman who presents to the
emergency department 12 hours after the onset of
abdominal pain. She is admitted to the hospital with
presumed biliary pancreatitis. She states she has nausea
and abdominal pain. Laboratory test results are as follows: amylase, 690 U/L; total bilirubin, 4.1 mg/dL;
hemoglobin, 16 mg/dL; leukocyte count, 21 ×
103/mm3; aspartate aminotransferase (AST), 67 U/L;
lactic dehydrogenase (LDH), 220 U/L; glucose,
189 mg/dL; and alkaline phosphatase levels, 310 U/L.
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Nonbiliary
Pancreatitis
Time
Biliary
Pancreatitis
Admission
Age (yr)
3
3
> 55
> 70
Leukocytes (× 10 /mm )
> 16
> 18
Blood glucose (mg/dL)
> 200
> 220
LDH (U/L)
> 350
> 400
AST (U/L)
> 250
> 250
Hematocrit decrease
(points)
> 10
> 10
BUN increase (mg/dL)
>5
>2
Serum calcium (mg/dL)
<8
<8
PaO2 (mm Hg)
< 60
< 60
Base deficit (mEq/L)
>4
>5
Fluid requirement (L)
>6
>4
AST = aspartate aminotransferase; BUN = blood urea nitrogen; LDH =
lactic dehydrogenase; PaO2 = arterial oxygen partial pressure.
*Three or more Ranson criteria within 48 hours of onset of acute
pancreatitis suggest severe acute pancreatitis.
• Is this patient a candidate for intensive care unit
(ICU) admission?
DISCUSSION
Ranson’s Criteria
Because of the propensity for acute pancreatitis to
progress into multisystem organ failure, a mechanism
to predict its severity and to allocate treatment resources is essential. Ranson’s criteria take into consideration 11 clinical findings over a 48-hour period
(Table 4). Three or more Ranson’s criteria within
48 hours of onset of acute pancreatitis suggest severe,
acute pancreatitis. Patients with 1 or 2 criteria have a
predicted mortality of 1%, which increases to 10% for
3 criteria and to 50% for patients with 7 or more criteria. The major limitations of Ranson’s criteria are that
complete assessment requires data that may not be
available until 48 hours after admission and that these
criteria cannot be calculated serially at later times during hospitalization. This particular patient meets one
criterion; therefore, she is at a reduced risk for developing complicated pancreatitis and does not require
triage to the ICU.
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C o n t e m p o r a r y Tr e a t m e n t o f A c u t e P a n c r e a t i t i s
Table 5. Physiologic Variables for APACHE II Severity
of Disease Classification*
Temperature
Mean arterial pressure
Pulse
Respirations
PaO2
Arterial pH
Serum Na+
Serum K+
Serum creatinine
Hematocrit
Leukocyte count
Glasgow coma score
*The APACHE II score is derived by adding points calculated by
assessing these variables to points based on age and chronic health
characteristics. A score of > 8 denotes severe acute pancreatitis.
APACHE = acute physiology score and chronic health evaluation.
Glasgow Score
This scoring system is more popular in Europe. It utilizes 8 clinical criteria similar to the Ranson’s criteria.
Acute Physiology Score and Chronic Health
Evaluation (APACHE II)
The APACHE II scoring system is a severity-of-illness
index that overcomes the limitations of Ranson’s criteria
but is cumbersome to calculate. It utilizes 12 physiologic
and laboratory parameters available at admission, as well
as age and preexisting comorbid conditions (Table 5).
The APACHE II score can be calculated on a daily basis,
thus providing a mechanism to serially evaluate the disease process. An APACHE II score higher than 8 denotes severe acute pancreatitis.13
Multi-Organ Dysfunction Score (MODS)
More recently, many investigators have employed
this end-organ injury–based scoring system to predict
the severity of acute pancreatitis. A MODS of 2 or more
seems to predict early mortality.14
Biochemical Assays
The central role of cytokines in the pathogenesis of
pancreatitis has been well established. With the possible
exception of interleukin 6 (IL-6) and IL-8, many biochemical markers of acute pancreatitis and inflammation
have not been proven to be superior to the clinical scoring systems in predicting the severity of pancreatitis.15 De-
6 Hospital Physician Board Review Manual
spite their predictive value, clinical use of IL-6 and IL-8
levels has been hindered by the lack of a rapid assay. The
utility of trypsinogen-activating peptide and C-reactive
protein as predictors of severity has been shown in small
studies and warrants further investigation.16
FURTHER CLINICAL MANIFESTATIONS IN PATIENT 2
Within hours of admission to the ward, the case
patient develops tachycardia, tachypnea, oliguria, and
hypotension. Laboratory data are as follows: total
bilirubin, 6.3 mg/dL; leukocyte count, 29 × 103/mm3;
blood urea nitrogen, 32 mg/dL; and arterial oxygen
partial pressure (PaO2), 61 mm Hg on room air. Her
APACHE II score is 10.
• What treatment plan should this patient receive after
initial stabilization in the ICU?
Discussion
Although Ranson’s criteria predicted a mild pancreatitis, this patient’s clinical condition took a different
course. Her clinical course reflects the pathophysiology of
systemic super inflammation during severe pancreatitis,
and her clinical manifestations are a result of circulating
inflammatory cytokines (Figure 1). The fundamental
pathophysiologic event of acute pancreatitis is injury to
acinar cells, after which inflammatory cytokines (IL-1,
IL-6, IL-8, and tumor necrosis factor) are produced by
leukocytes that invade the pancreas. After a latent period,
cytokines are produced to a larger extent in the lungs and
the liver by macrophages and neutrophils that are activated by circulating pancreatic enzymes.17–19
In these patients, aggressive fluid and electrolyte resuscitation should be undertaken to correct and prevent
further hypovolemia and prerenal azotemia. Supplemental oxygen should be administered and mechanical
ventilation should be carried out in the event of respiratory insufficiency. Invasive monitoring (pulmonary
artery catheter, arterial line) should be undertaken as
clinical circumstances dictate.
Currently, the mainstay of treatment of acute pancreatitis is supportive (Figure 2). The term “bowel rest”
is misleading and is not based on a current understanding of pancreatitis. In acute pancreatitis, the
pancreas is in a state of hyperinflammation and autodigestion, and further stimulation by food may be clinically insignificant. Most experts advocate resumption of
oral intake as soon as it can be tolerated. However, patients should be given nothing by mouth until ileus
resolves. Routine nasogastric tube use should be reserved for patients with severe pancreatitis or for those
demonstrating signs of gastric outlet obstruction.
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C o n t e m p o r a r y Tr e a t m e n t o f A c u t e P a n c r e a t i t i s
Pain control is an important aspect of treatment and
should be carried out diligently; narcotics usually are
needed. The theoretical disadvantage of morphineinduced spasm of the sphincter of Oddi has not been
shown to be of any clinical significance. Prophylaxis for
deep venous thrombosis is required as well. Most surgeons also institute acid suppression.
The use of prophylactic antibiotics has become a hotly
debated issue. A meta-analysis demonstrated that prophylactic antibiotics reduce morbidity and mortality of
severe acute pancreatitis.20 However, a recent placebocontrolled, double-blind study of ciprofloxacin/
metronidazole did not detect any difference in the risk
of developing infected pancreatic necrosis with the use
of prophylactic antibiotics versus placebo.21 Moreover,
the benefit of prophylactic antibiotics in acute mild pancreatitis is not well established. Imipenem is the antibiotic of choice because it has superior concentration in
the pancreatic parenchyma (including the necrotic pancreatic tissue) and has a broad spectrum of activity.22
Empiric antifungal therapy with fluconazole is recommended because fungal infections in severe pancreatitis
can potentially result in significant morbidity.23 Use of
the sandostatin analogue in managing acute pancreatitis has been controversial because of a lack of demonstrable benefit.1 Newer generation antibiotics with similar penetration in the pancreas have not been evaluated
clinically, but they may find a role in the future.
Nutritional support should be instituted promptly
after hemodynamic stability has been established. Initially, parenteral administration is the most practical
route for nutritional support because of many considerations, including fluid and electrolyte shifts as well as
ileus. Parenteral nutrition should be switched to enteral nutrition as soon as the latter can be tolerated. The
normal increase in pancreatic secretions in response to
intravenous lipid infusions has not been shown to worsen the course of pancreatitis. Once the ileus has resolved, feedings can be given orally or through a jejunal
feeding tube.
At least 4 clinical trials have demonstrated that endoscopic sphincterotomy can effectively relieve biliary obstruction and reduce morbidity of biliary sepsis during
pancreatitis, but its effects on the overall mortality are
not as clear.1 To achieve these outcomes, ERCP should
be carried out in the first 24 hours after onset of severe
pancreatitis to assess whether biliary obstruction is present; endoscopic sphincterotomy can be performed during the ERCP. This patient’s laboratory data strongly
suggest biliary obstruction, and she is within the initial
24- to 48-hour window; therefore, she is a candidate for
ERCP. The risk of routine early ERCP (especially in
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Alcohol, gallstones, hyperlipidemia, trauma, etc
Acinar cell injury
Acute pancreatitis
Immunocompetent cells
TNF
ILs
NO
PAF
SIRS
Renal failure
Pulmonary failure
Vascular leakage
Hypovolemia
Cardiac dysfunction
Figure 1. The role of inflammatory mediators in acute pancreatitis. Immunocompetent cells produce tumor necrosis factor (TNF), interleukins (ILs), nitric oxide (NO), and platelet
activation factor (PAF) in response to stimulation by pancreatic enzymes. Cytokines induce the clinical picture associated
with the systemic inflammatory response syndrome (SIRS).
mild pancreatitis) outweighs its benefits. Patient 2 undergoes ECRP, and small stones are recovered from the
bile duct.
Treatment of hyperlipidemia should prevent recurrences in most cases. Cholecystectomy for cholelithiasis
should be carried out for all patients with gallstone pancreatitis as well as for all patients with recurrent or idiopathic pancreatitis. Most surgeons recommend cholecystectomy during the same hospitalization as soon as
the pancreatitis has resolved and the patient is nearing
discharge. Abstinence from alcohol reduces the recurrences of alcoholic pancreatitis.
FURTHER PRESENTATION OF PATIENT 2
One week later, a CT scan is performed because of
continued fever (Figure 3A). The radiologist offers to
drain the easily accessible fluid collection or “pseudocyst” in the lesser sac.
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C o n t e m p o r a r y Tr e a t m e n t o f A c u t e P a n c r e a t i t i s
Acute pancreatitis
Severe
ICU admission, NPO, NG tube, fluid resuscitation, pain control
Support body system (O2, mechanical ventilation)
Prophylactic antibiotics/antifungals
Early ERCP if indicated (see text)
Nutritional support (TPN/enteral)
Treat underlying etiology
Pancreatitis-directed therapeutics?
Mild
NPO, IV fluids, pain control
Supportive treatment
Treat underlying etiology (eg, gallstones)
Pancreatitis-directed therapeutics?
sen
or
W
Improve
Fail
Discharge
Infected necrosis
Sterile necrosis
CT scan, FNA
Respond
Maximize nonoperative treatment for 24–48 h
Operative débridement
Worsen
Respond
Improve
Figure 2. Algorithm for the treatment of acute pancreatitis. CT = computed tomography; ERCP = endoscopic retrograde cholangiopancreatography; FNA = fine needle aspiration; ICU = intensive care unit; IV = intravenous; NG = nasogastric; NPO = nothing by mouth; TPN = total parenteral nutrition.
• What is the role of nonoperative drainage of pancreatic fluid collections?
Discussion
This patient developed acute pancreatic fluid collections (Figure 3A) that are commonly but erroneously
called phlegmon (small fluid component) or pseudocysts (predominant fluid component). These peripancreatic fluid collections can regress spontaneously (Figure 3B) or may persist to form a pseudocyst. This
patient has no evidence of infected pancreatic necrosis
or pancreatic abscess and therefore drainage is not indicated at this time.
CASE 2 FOLLOW-UP
The surgeon does not drain the acute peripancreatic fluid collection. The patient recovers from respiratory failure after 6 days of endotracheal intubation.
Aggressive fluid resuscitation prevents her from progressing into renal failure. She receives antibiotics, and
her fever resolves in 4 days. She is transferred to the surgical ward after 8 days in the ICU.
8 Hospital Physician Board Review Manual
CASE 3
PATIENT PRESENTATION
Patient 3 is a 52-year-old woman who is admitted to
the ICU with severe acute pancreatitis and acute respiratory distress syndrome (ARDS). Despite aggressive supportive treatment, she develops hypotension, tachycardia, and increased serum creatinine. An abdominal CT
scan is performed (Figure 4). The results of laboratory
tests are: alkaline phosphatase level, 320 U/L; leukocyte
count, 20 × 103/mm3; glucose, 310 mg/dL; LDH,
380 U/L; and AST, 300 U/L. Her APACHE II score is 12.
SEVERE PANCREATITIS WITH PANCREATIC NECROSIS
Approximately 2% to 5% of patients develop severe
acute pancreatitis associated with pancreatic necrosis
and may require operative intervention. The CT scan in
Figure 4 shows necrotizing pancreatitis because the
body and tail of the pancreas are not enhanced after an
intravenous contrast bolus (> 30% of the parenchyma).
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C o n t e m p o r a r y Tr e a t m e n t o f A c u t e P a n c r e a t i t i s
A
A
B
Figure 3. Computed tomography demonstrating an acute peripancreatic fluid collection. (A) Note irregularly shaped fluid collection anterior to the pancreas (arrows) that resolved spontaneously 6 weeks later (B). (Reprinted with permission from
Bradley EL 3rd. Clinically based classification system for acute pancreatitis and regional complications. Probl Gen Surg 1997;13:121.)
As with mild forms of pancreatitis, the mainstay of initial treatment in severe necrotizing pancreatitis is supportive, as outlined in the algorithm (Figure 2). The
role of operative treatment in patients with necrotizing
pancreatitis continues to evolve. However, the consensus is that operative treatment is indicated in patients
who develop infected necrosis or who continue to deteriorate despite maximal nonoperative treatment
whether or not they have infected necrosis.24,25 In patients who are suspected of having infected necrosis,
sampling the necrotic areas in the lesser sac via CTdirected fine needle aspiration can confirm the diagnosis. Findings of extravisceral air on CT would indicate
the need for operative débridement in the appropriate
clinical setting because extraluminal gas is indicative of
infected necrosis or peripancreatic abscess. Regarding
this patient, a necrosectomy should be entertained if
she does not respond to aggressive resuscitative measures within the next 24 to 48 hours.
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B
Figure 4. Computed tomography demonstrating pancreatic
necrosis. (A) Only the head of the pancreas enhances after an
intravenous contrast bolus, which is characteristic of massive pancreatic necrosis; the patient was managed without surgical débridement. (B) Repeat scan 16 months later demonstrates a normally enhancing pancreatic head but no contrast in body and tail.
Percutaneous biopsy of nonenhancing area of the gland showed
only fibrous tissue. (Reprinted with permission from Bradley EL
3rd. Clinically based classification system for acute pancreatitis and
regional complications. Probl Gen Surg 1997;13:122.)
The rationale for operative treatment is to remove
the necrotic peripancreatic and pancreatic tissue that
acts as a reservoir for infection and sepsis. Surgical
techniques for managing ongoing necrosis in the
lesser sac after the initial necrosectomy include wide
drainage (closed packing), high volume closed lavage,
or open packing.24 A more aggressive approach of
repeated planned necrosectomy every 48 hours involves closing the abdominal wall with a zipper; this
approach has resulted in a low rate of recurrent abdominal abscesses and incisional hernias25 (Figure 5).
Mortality of operative treatment of necrotizing pancreatitis ranges from 7% (closed packing)25 to 22%
(planned necrosectomy),26 which is more favorable than
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for a routine visit 6 weeks after developing an episode
of mild pancreatitis. She has minimal epigastric discomfort and is tolerating regular food. She has an
abdominal CT scan done by another physician the previous week that demonstrates a 5-cm pseudocyst in the
lesser sac.
• What is the rationale for operative treatment of
pseudocysts?
Figure 5. Repeated planned necrosectomy includes placement
of drains and a zipper in the abdominal wall fascia to facilitate
repeated debridement and to minimize loss of abdominal domain.
Repeated debridement is undertaken until all the necrotic tissue
has been removed and granulation tissue becomes apparent.
the uniformly fatal outcome of untreated infected pancreatic necrosis. It has become clear that in the appropriate clinical setting (stable patient, mild symptoms)
postponing necrosectomy may carry a more favorable
outcome; however, waiting longer than 28 days is of no
additional benefit.26 Long-term outcomes after necrosectomy are characterized by pancreatic endocrine
and/or exocrine insufficiency in 50% of the patients.27
Percutaneous catheter aspiration or drainage
achieves little in the evacuation of the thick necrotic
material and augments the risk of infection; therefore,
this method is not recommended. Endoscopic transgastric drainage of pancreatic necrosis and pseudocysts is
an exciting new approach for patients in whom the
necrotizing process is limited to the lesser sac and who
are considered high risk for operative treatment.28
Pancreatic resection and peritoneal lavage have no
proven role in the treatment of necrotizing pancreatitis.
CASE 3 FOLLOW-UP
The patient is managed nonoperatively and recovers
after 30 days in the ICU.
CASE 4
PATIENT PRESENTATION
Patient 4 is a 24-year-old woman who has returned
10 Hospital Physician Board Review Manual
DISCUSSION
Less than 10% of all patients with acute pancreatitis
develop pseudocysts, which are more common with
alcoholic than biliary pancreatitis.29,30 Acute peripancreatic fluid collections that are found within a few weeks
from the onset of pancreatitis should not be mistaken
for or treated as if they were pseudocysts. Pseudocysts of
the pancreas most commonly occur as a result of pancreatitis and disruption of the pancreatic duct. The
extravasated pancreatic fluid is walled off by a dense
inflammatory reaction. Thus, the lining of a pseudocyst,
which takes weeks to form, is nonepithelial granulation
tissue and is made from the surrounding viscera. Symptoms arise from compression of adjacent organs, causing
abdominal pain, nausea, vomiting, or jaundice.
The ready availability of imaging modalities has
helped elucidate the natural history of pseudocysts. Recently, it became apparent that not all pseudocysts require operative treatment because many resolve spontaneously. The treatment of pseudocysts has evolved
over the years from recommending operative drainage
in all pseudocysts larger than 6 cm to a more selective
approach. Two reports demonstrate that selective nonoperative management of pseudocysts is successful in
50% to 60% of asymptomatic patients irrespective of
pseudocyst size.29,30 Patients who are treated expectantly should be monitored closely for the development of
complications (10%) that require prompt intervention.
Rupture of a pseudocyst may be accompanied by intraabdominal hemorrhage and sepsis. Bleeding into a
pseudocyst can result in severe abdominal pain and
shock; emergency angiographic control of the bleeding
vessel has become widely accepted.29,30 Pancreatic
ascites and pleural effusion from a disrupted pancreatic duct can be treated with hyperalimentation, aspiration of ascites or pleural effusions, and transpapillary
stenting of the pancreatic duct.
In this particular patient, management of the
pseudocyst should take into consideration the clinical
presentation (symptomatic versus asymptomatic, presence of complications) and resolution of pancreatitis.
Patient 4 may require no further treatment than a
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C o n t e m p o r a r y Tr e a t m e n t o f A c u t e P a n c r e a t i t i s
cholecystectomy, especially because she is asymptomatic, and her pseudocyst may resolve without further
intervention. The presence of symptoms and the
“maturing” period of 6 weeks should be the principal
factors in determining whether a pseudocyst should be
drained.
Infected pseudocysts should be drained externally
because they contain debris and necrotic material that
will not be adequately drained by small caliber percutaneous drains. Enteric internal drainage of sterile pseudocysts can be achieved by anastomosing the pseudocyst
wall to the stomach, jejunum, or duodenum. New endoscopic approaches have yielded encouraging results, but
their long-term outcome is not known. Laparoscopic
drainage is an appealing alternative, especially when a
biopsy of the pseudocyst wall is desired in patients with a
“less than typical” history of acute pancreatitis. Recent
evidence shows that percutaneous drainage of pseudocysts is acceptable in patients with normal pancreatic
duct anatomy and results in satisfactory outcomes and
resolution of pancreatic fluid collections.31
CASE 4 FOLLOW-UP
A CT scan is repeated 3 weeks later, and it shows
almost complete resolution of the pseudocyst. Subsequently, the patient undergoes laparoscopic cholecystectomy and recovers without incident. It is essential
that the pseudocyst resolve before the cholecystectomy;
open cholecystectomy may be indicated when laparoscopy cannot be done.
SUMMARY POINTS
• The spectrum of clinical presentations of acute pancreatitis depends on the severity of disease process.
• No single laboratory test or physical finding is
pathognomonic for pancreatitis. The cardinal clinical symptom of acute pancreatitis is constant epigastric pain of insidious onset, often radiating to the
back. Other clinical findings include anorexia, fever,
nausea, vomiting, ileus, and abdominal distention.
• Contrast-enhanced dynamic CT has become the
standard test used to evaluate patients with acute
pancreatitis. However, ultrasonography is useful in
mild cases to assess for gallstones.
• Currently, the mainstay of treatment of acute pancreatitis remains supportive.
• Approximately 2% to 5% of patients develop severe
pancreatitis that is associated with pancreatic necrosis and is responsible for 90% of the mortality from
acute pancreatitis.
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• The rationale for operative treatment is removal of
the necrotic peripancreatic and pancreatic tissue that
acts as a reservoir for infection and sepsis.
• Acute peripancreatic fluid collections found within a
few weeks from the onset of pancreatitis tend to resolve
spontaneously. Acute fluid collections should not be
mistaken for or treated as if they were pseudocysts.
• Nonoperative management of pseudocysts is successful in 50% to 60% of asymptomatic patients irrespective of pseudocyst size.
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12 Hospital Physician Board Review Manual
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