THE AMERICAN JOURNAL OF GASTROENTEROLOGY

2002 by Am. Coll. of Gastroenterology

Published by Elsevier Science Inc.

Vol. 97, No. 6, 2002

ISSN 0002-9270/02/$22.00
PII S0002-9270(02)04122-9

A Critical Evaluation of Laboratory Tests in Acute

Pancreatitis
Dhiraj Yadav, M.D., N. Agarwal, M.D., F.R.C.S., and C. S. Pitchumoni, M.D., M.A.C.G.
Division of Gastroenterology and Department of Surgery, Our Lady of Mercy University Medical Center,
New York Medical College, Bronx, New York

ABSTRACT

INTRODUCTION

An ideal laboratory test in the evaluation of a patient with

acute pancreatitis (AP) should, in addition to accurately
establishing the diagnosis of AP, provide early assessment
of its severity and identify the etiology. None of the tests
available today meet all these criteria, and presently there is
no biochemical test that can be considered the gold standard for the diagnosis and assessment of severity of AP. In
the diagnosis of AP, serum amylase and lipase remain
important tests. Advantages of amylase estimation are its
technical simplicity, easy availability, and high sensitivity.
However, its greatest disadvantage is its low specificity. A
normal amylase would usually exclude the diagnosis of AP,
with the exception of AP secondary to hyperlipidemia, acute
exacerbation of chronic pancreatitis, and when the estimation of amylase is delayed in the course of the disease. The
major advantage of lipase is an increased sensitivity in acute
alcoholic pancreatitis and in patients who initially present to
the emergency room days after the onset of the disease, as
lipase remains elevated longer than amylase. Although once
considered to be specific for AP, nonspecific elevations of
lipase have been reported in almost as many disorders as
amylase, thus decreasing its specificity. Simultaneous estimation of amylase and lipase does not improve the accuracy. Other enzymes for the diagnosis of APpancreatic
isoamylase, immunoreactive trypsin, and elastaseare
more cumbersome and expensive and have no clear role in
the diagnosis of AP. No enzyme assay has a predictive role
in determining the severity or etiology of AP. Once the
diagnosis of AP is established, daily measurements of enzymes have no value in assessing the clinical progress of the
patient or ultimate prognosis and should be discouraged. A
host of new serological and urinary markers have been
investigated in the last few years. Their main use is in
predicting the severity of AP. At present, serum C-reactive
protein at 48 h is the best available laboratory marker of
severity. Urinary trypsinogen activation peptides within
1224 h of onset of AP are able to predict the severity but
are not widely available. Serum interleukins 6 and 8 seem
promising but remain experimental. (Am J Gastroenterol
2002;97:1309 1318. 2002 by Am. Coll. of Gastroenterology)

The diagnostic tests in the evaluation of a patient with

suspected acute pancreatitis (AP) must answer three questions sufficiently early in the course of the disease: first and
foremost, the tests should establish the diagnosis accurately,
excluding other conditions that mimic AP with or without
hyperamylasemia. Second, at the earliest they should provide an assessment of severity of AP to provide appropriate
treatment in the required setting: intensive care unit versus
a regular floor or by an internist alone versus a team of
medical specialists that includes a surgeon, radiologist, and
gastroenterologist trained in therapeutic endoscopy. Third,
tests should also help in establishing the etiology for AP, so
as to offer a definitive treatment such as cholecystectomy
and/or to prevent recurrences of AP, as in the case of a
patient with hyperlipidemic AP. The tests should be easily
available, cost-effective, and easily repeatable. Obviously,
every patient should not undergo all tests.
This article, an extension of a number of recent reviews
on the topic, including ours published in 1990 in this journal
(1), critically evaluates the standard serum and urine tests
and discusses the advances in laboratory technology that
may have new diagnostic possibilities. In addition to our
previous article on this topic (1), we have included relevant
articles after 1990, using a broad-based MEDLINE search
using the terms acute pancreatitis, diagnosis, laboratory
tests, and severity. Relevant articles as well as their references were reviewed.

SERUM TESTS FOR DIAGNOSIS OF AP

A host of serum enzymes such as amylase, lipase, trypsinogen, elastase, phospholipase A2, ribonuclease, etc are available to diagnose AP and/or to assess the severity, but elevated amylase levels continue to be the gold standard
among the serum markers.
Serum Amylase
In AP, serum amylase rises as a result of both increased
release and, to some extent, reduced catabolism. The most
familiar units of expression are the Somogyi unit (SU) and
the international unit (IU). One SU per 100 ml is equivalent
to 1.85 IU/L. The normal values are 60 160 SU/100 ml or

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Yadav et al.

110 300 IU/L in serum and 35260 SU/h or 65 480 IU/L

in urine (2).
SENSITIVITY. The sensitivity of any test is dependent on
the criteria used for diagnosis. If the test itself is taken as a
criterion for diagnosis, as is often the case for serum amylase in AP, its sensitivity will be artificially raised to 100%
(3). In one cohort (4), a 99.6% sensitivity for serum amylase
reflected such subjective inclusion criteria. However, the
sensitivity decreases to 8195% when CT scan or ultrasound is used to ascertain the clinical diagnosis of AP (5, 6).
Normoamylasemia is reported in 19 32% of patients
with AP (6, 7). Diagnosis of AP is questioned if the amylase
level is normal. However, there are three major factors that
lower the sensitivity:
1. Time interval since onset of attack. A major confounding
factor is the variable time elapsed between the onset of
the symptoms and the first blood analysis in a given
patient. Within 24 h of the onset of symptoms, all enzymes are elevated; thus, serum amylase is as sensitive as
serum lipase, pancreatic isoamylase (P-isoamylase), immunoreactive trypsin, or elastase (8). Amylase is the first
one to return toward normal values, and as such, after the
first hospital day it is the least sensitive of the enzymatic
tests for pancreatitis. Normalization can sometimes occur
very rapidly, indicating early resolution of the disease,
increased urinary clearance, or, less frequently, extensive
destruction of the pancreas with cessation of pancreatic
amylase production (6).
2. Alcoholic pancreatitis. Spechler et al. (7) noted that
patients with acute alcoholic pancreatitis frequently
(32%) have normal serum amylase levels. Furthermore,
in patients with alcoholic AP, normoamylasemia was
significantly associated with number of previous attacks
(0.7 vs 0.4, p 0.01), indicating a parenchyma that is no
longer able to produce sufficient amounts of enzymes
(6).
3. Hypertriglyceridemia. Serum or urinary amylase levels
may be normal in as many as 50% of patients with
abdominal pain and hypertriglyceridemia, in whom a
clinical diagnosis of AP is considered and when CT
shows pancreatic inflammation (9). The hyperlipidemia
interferes with the amylase assay, leading to a spuriously
normal result. A circulatory inhibitor of serum amylase
exists, as suggested by demonstration of elevated amylase by dilution of the serum (10), but is probably not
triglyceride itself (11). In all situations where AP is
suspected with a normal serum amylase, triglyceride
estimations must be done, and if lactescent plasma is
present, serial dilution techniques should be employed to
circumvent false negative amylase results.
SPECIFICITY. The greatest limitation of serum amylase is
its lack of specificity. Besides AP, conditions that increase
serum amylase levels include many diseases and derangements of the biliary tract, liver, intestines, genitourinary

AJG Vol. 97, No. 6, 2002

Table 1. Conditions With Increased Amylase

Abdominal disorders
Pancreatic disorders: acute pancreatitis, chronic pancreatitis,
pseudocysts, pancreatic trauma, pancreatic cancer
Nonpancreatic intra-abdominal conditions: perforated bowel,
mesenteric infarction, intestinal obstruction, appendicitis,
peritonits, abdominal aortic aneurysm, ruptured ectopic
pregnancy, fallopian and ovarian cysts, salpingitis, hepatitis
Extra-abdominal conditions
Salivary diseases, renal failure, ketoacidosis, pneumonia,
cerebral trauma, burns, anorexia nervosa, bulimia,
nonabdominal surgery
Macroamylasemia
Idiopathic hyperamylasemia
Familial and nonfamilial
Drug induced
Definite association: azathioprine, L-asparginase,
sulfonamides, tetracycline, didanosine, methyldopa, estrogens,
furosemide, pentamidine, 5-aminosalicylic acid compounds,
valproic acid, salicylate, thiazide, calcium, vinca alkaloids
Probable association: glucocorticoids, nitrofurantoin,
phenformin, rifampin, FK-506 (tacrolimus), metronidazole,
6-mercaptopurine, procainamide, diphenoxylate,
chlorthalidone, cimetidine, cytosine arabinoside, cisplatin,
cyclosporin A

tract, lungs, breast, prostate, central nervous system, and, of

course, salivary glands (12). Abnormal serum levels also
occur in the presence of metabolic disturbances such as
renal failure, liver dysfunction, diabetic ketoacidosis, hypoperfusion, eating disorders like anorexia nervosa and bulimia (13), and abdominal and nonabdominal trauma including head injury, as well as with the use of various drugs (2,
14). Interestingly, hyperamylasemia, seen commonly in
HIV-infected persons and in up to 40% of intoxicated alcoholics, often does not signify AP, as predominantly Stype amylase levels alone go up (15, 16). An important
observation is that, after ERCP, hyperamylasemia is noted
in 25 43% of patients but only 1 4% have evidence of
pancreatitis (17). Furthermore, persistent hyperamylasemia
may be a normal variant (18) and has been recently described as a benign abnormality in many members of certain
families (19) (Table 1).
Another critical limiting factor that significantly influences the specificity is the issue of what signifies an abnormal value (3). More than 200 techniques of amylase determination are described in the literature, creating a host of
normal values that differ both quantitatively and in methods of expression (2, 20). Further, different studies have
arbitrarily used various cutoff values ranging from just the
upper limit of normal (300 IU/L) (3) to more than three
times the upper limit of normal (1000 IU/L) (21). No
international reference method or cutoff value has yet been
adopted toward establishing a standardized tool. With a
cutoff value of 300 IU/L (upper limit of normal), total
amylase has a sensitivity of 91100% but a specificity of
7198%. Increasing the cutoff value to 1000 IU/L increases
the specificity to around 100% but decreases sensitivity to as
low as 61%. Ideally, sensitivity should be increased at the

AJG June, 2002

expense of specificity when the penalty associated with

missing the disease is high. On the other hand, specificity
should be increased relative to sensitivity when the costs or
risks associated with further diagnostic techniques are substantial. Because AP can be serious, it is wiser to increase
the sensitivity at the expense of specificity.
SEVERITY OF AP. Virtually all investigators agree that
the magnitude of increase in amylase activity does not
correlate with the severity of the disease. It is even possible
for patients with very severe necrotizing AP to have normal
or low values of amylase, indicating an inverse relationship
between the amylase level and the severity of the disease
(22, 23). Clinically, AP does not seem to behave differently
when serum amylase is normal or elevated (6, 24). Once the
diagnosis of AP is established, daily measurements of serum
amylase have little value in assessing the clinical progress of
the patient or ultimate prognosis (25). However, persistent
hyperamylasemia that does not return to normal within 510
days has been shown to correlate with complications such as
pseudocysts, necrosis, or abscess.
ETIOLOGY OF AP. In general, patients with biliary pancreatitis have markedly higher initial serum amylase levels
than those with alcoholic pancreatitis or pancreatitis from
other causes. Hiatt et al. (26) observed that only 11% of
patients with biliary disease had initial serum amylase values lower than 1000 IU/L, whereas only 6% with alcoholic
pancreatitis had initial amylase values higher than 1000
IU/L.
CLINICAL PRACTICE RECOMMENDATIONS. The advantage of serum amylase estimation lies in its technical
simplicity and ready availability in all hospitals. In contrast,
its greatest disadvantage is its overall low specificity. Because the presence of a raised serum amylase in the clinical
setting of abdominal pain is not entirely specific, it is desirable to confirm it by imaging studies. A normal amylase
level would nearly exclude the diagnosis, with the exceptions of possible hyperlipidemic pancreatitis, acute exacerbation of chronic pancreatitis, and delayed estimation in the
course of the disease. Indeed, AP should not be dismissed in
the presence of an amylase level that is either normal or only
mildly elevated on initial evaluation if the clinical suspicion
for AP is high and it is prudent to seek additional tests.
Serum amylase has no value in assessment of severity or
etiology of AP.
Lipase
Lipase (triacylglycerol acylhydrolase) is mainly synthesized
and stored as granules in the pancreatic acinar cells. More
than 99% is subsequently excreted in the ductal systems,
and less than 1% diffuses via the lymphatics and capillaries
into the general circulation (27). The concentration gradient
between pancreatic tissue and serum is over 20,000-fold.
Other sources of lipase are the tongue, esophagus, stomach,
duodenum, leukocytes, adipose tissue, lung, and breast milk.

Evaluation of Laboratory Tests in Acute Pancreatitis

1311

However, the lipase concentration in the pancreas is 100fold greater than in the liver, duodenum, and small bowels
(28). In AP, increased permeability in the basal pole of the
acinar cells accounts for the pronounced rise of the enzyme
in the serum. Usually, serum lipase increases within 4 8 h
after onset of symptoms, peaks at 24 h, and returns to
normal after 8 14 days (29). Lipase assay is fast, reliable,
practical, and almost as sensitive as an amylase assay. The
cost of the lipase assay compares favorably with amylase
assays, and the technique can be available 24 h a day, 7 days
a week in most hospitals.
SENSITIVITY. The sensitivity of lipase ranges from 85%
to 100% (3, 21), with some reporting it to be less sensitive
than serum amylase (3) and others believing it to be more
sensitive than amylase (21, 30). The major advantage of
lipase is an increased sensitivity in acute alcoholic pancreatitis and with late clinical presentation, as lipase remains
elevated longer than does amylase. Clavien et al. (6) found
that in patients with AP who had normal amylase, more than
two thirds had elevated lipase levels. Gumaste et al. have
shown in their study on patients with AP and nonpancreatic
abdominal pain (31) that the sensitivity of lipase levels of
greater than three times normal is much higher than amylase
levels (100% sensitivity and 99% specificity, vs 72% sensitivity and 99% specificity for amylase levels). In a recent
study of ERCP-induced AP (32), mean lipase values were
four times higher than amylase levels 2 h after the procedure
in those who developed AP.
SPECIFICITY. Lipase elevation is not specific to AP, although it may be slightly better than amylase. Apple and
associates (30) have shown that lipase activity is four times
greater than amylase activity in the pancreas. Second, pancreatic tissue in chronic pancreatitis demonstrates a substantial decline in both amylase and lipase activity, with amylase
activity showing a greater decrease compared to lipase (91%
vs 26%). In conditions of extrapancreatic injury, lipase is
also elevated. Mumps, types I and IV hyperlipoproteinemias, peptic ulcer, acute cholecystitis, extrahepatic biliary
obstruction, liver diseases, small bowel obstruction, intestinal infarction, perforated bowel, acute renal failure, fracture
of bone, crush injury, fat embolism, and the postcholecystectomy syndrome are some examples (7, 33). In our study
of patients with diabetic ketoacidosis (34) we found nonspecific elevation of lipase to occur more frequently than
amylase elevation. Recently, inflammatory bowel disease
and familial pancreatic hyperenzymemia have been included among causes of lipase elevation (19, 35).
The reference point determined in different laboratories
may differ even for identical methods (27, 36). Further,
different authors have arbitrarily used different cutoff values. Steinberg et al. (3) have shown that the upper limit of
normal itself provided the best cutoff value. Keim and
associates (5) suggest that 2-fold elevated lipase values
should be used as the cutoff, whereas Gumaste et al. (31)

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Yadav et al.

advocate a cutoff level of three times normal. They observed

that when lipase elevation is not due to AP, the elevation is
usually less than three times normal. However, Frank and
Gottlieb (29) have reported patients with lipase greater than
three times normal secondary to renal insufficiency, malignant tumors, cholecystitis, esophagitis, and hypertriglyceridemia. Other major disadvantages of lipase assay are a)
presence of as many as four fractions of lipase in serum of
patients with pancreatitis, b) the macroforms or macrolipasemia contribute to hyperlipasemia, and c) technical difficulties are more with lipase assays than amylase assays
(27, 36, 37).
CLINICAL PRACTICE RECOMMENDATIONS. The
major advantage of lipase is an increased sensitivity in acute
alcoholic pancreatitis and late clinical presentation, as lipase
remains elevated longer than amylase. Its specificity may be
slightly better than amylase; however, it is increasingly
being recognized that nonspecific elevations of lipase can be
seen in as many disorders as amylase. Serum lipase also has
no value in assessment of severity or etiology of AP.
Amylase, Lipase, or Both
Controversy exists whether amylase and lipase should be
used alone or in combination to avoid overlooking patients
with AP. Opinions vary on the preferential test (38). Although amylase continues to be the screening test for AP (3,
6, 39), a number of studies have challenged the primary
diagnostic role of serum amylase, and a case has been made
for the use of serum lipase instead (31, 40, 41).
Within 24 h after onset of symptoms, both amylase and
lipase values have high sensitivity and specificity, with
lipase having a slightly higher diagnostic value. Amylase
appears to be a better test in gallstone pancreatitis and lipase
from alcoholic and other causes. The differences in performance of the two tests, though small, are definite (42).
Simultaneous evaluation of amylase and lipase does not
improve the accuracy (5, 43).
Other Tests of Limited or No Value
Normal circulating amylase consists of P-isoamylase (40%
of total amylase) and a salivary-type isoamylase (60%) (18).
In AP, P-isoamylase is expected to rise; hence the estimation of this fraction is theoretically attractive. Importantly,
some nonpancreatic abdominal emergencies such as acute
biliary tract disease, perforated duodenal ulcer, intestinal
obstruction, infarction, and ruptured abdominal aortic aneurysm are also associated with an increase in P-isoamylase.
Thus, a major group of differential diagnoses is not eliminated (44), and therefore, measurement of isoenzymes in the
serum has been largely abandoned (25).
Macroamylases are large molecules of amylase where
abnormal proteinsIgA, IgG, or IgMproduce a large
molecular weight complex that cannot be cleared through
the kidneys (45). It occurs in 0.1% of the population (46)
and in up to 2.7% of hospitalized patients (47). In a large
majority of individuals macroamylasemia is not clinically

AJG Vol. 97, No. 6, 2002

significant. However, in an asymptomatic individual with

elevated serum amylase, which causes concern, an estimation of urine amylase that shows low levels will settle the
issue.
Immunoreactive trypsinogen (IRT) has a sensitivity of
97100%, a specificity of 83%, and a positive predictive
value of 46 74% (3, 8). However, the levels are also high
in malignant neoplasms of the pancreas, diabetes mellitus,
chronic renal failure, hypercalcemia, hypertriglyceridemia,
cirrhosis of the liver, chronic pancreatitis, and extrahepatic
obstructive jaundice (48). Therefore, many believe that IRT
helps to confirm the pancreatic origin of a raised serum
amylase, but does not much improve the diagnostic accuracy in patients with suspected AP with normal or only
mildly elevated amylase. IRT is a more difficult test to
perform and requires 24 h to complete.
Elastase-1, a proteolytic enzyme liberated in the course of
AP, has a specific elastolytic action that is responsible for
digestion of blood vessel walls and vascular complications.
By radiommunoassay, one can demonstrate elevated elastase levels in the serum in all cases of AP. The test, however,
lacks specificity, as it is elevated in two thirds of pancreatic
cancer patients and less frequently in chronic pancreatitis
(17). Also, serum elastase levels did not correlate with
disease severity or development of complications. It is also
unable to discriminate between alcohol and gallstone pancreatitis (8). Elastase confers no benefit as a diagnostic test
nor does it provide any prognostic information. The only
strength of IRT and elastase assays is that they remain
elevated for 710 days after the onset of AP, and elastase is
the more sensitive of the two. Their determination may be
indicated in patients who present late and in whom the
diagnosis of pancreatitis is in doubt.
CLINICAL PRACTICE RECOMMENDATIONS. Presently, there is no role of isoamylases, IRT, macroamylases,
and elastase estimations in the routine management of patients with AP.

SERUM MARKERS OF SEVERITY OF AP

Hematocrit
Recently, hemoconcentration has been identified to be a
strong risk factor and early marker for necrotizing pancreatitis and organ failure (49, 50). An admission Hct of 47
and a failure of admission Hct to decrease at 24 h represent
a strong risk factor for the development of pancreatic necrosis. Baillargeon et al. (49) compared 32 patients with
necrotizing pancreatitis to an equal number of patients with
mild pancreatitis. At 24 h, 81% (26/32) of patients met
either of the criteria (admission HCT 47 or failure of HCT
to decrease), compared to 12.5% (4/32) of those with mild
AP (p 0.01). The sensitivity and specificity using these
criteria on admission were 34% and 91% and, at 24 h, 81
and 88%, respectively.

AJG June, 2002

C-Reactive Protein (CRP)

Serum CRP is an acute phase reactant that is elevated in
several inflammatory conditions and serves as a nonspecific
marker for inflammation. CRP levels peak on the 3rd or 4th
day, and values of 150 mg/L when done 48 h after the
onset of symptoms are now accepted as a proven predictor
of severity of AP (42). In a study by Wilson et al. (51), peak
CRP levels of 210 mg/L were able to differentiate severe
AP from the milder form with a sensitivity of 83 84% and
a specificity of 74 85%. Another recent study (52) has
shown CRP to be superior to interleukin 1B (IL-1B), IL-8,
and tumor necrosis factor (TNF-) and equivalent to IL-6
in predicting severe pancreatitis on day 2. CRP has also
been reported to have an overall accuracy of 93% in detecting pancreatic necrosis. Serum CRP therefore is considered
to be the gold standard for predicting severity of AP (51
55).
CRP is widely available, easy to measure, and cheap to
perform. The major drawback of CRP is that it takes 48 72
h to peak, a delay similar to other methods used for severity
assessment in AP.
Polymorphonuclear Elastase
In severe AP, neutrophils accumulate in the pancreas, producing lysosomal proteasesmainly elastaseand a major
factor for pancreatic necrosis. It also causes activation of
complement, kinins, and fibrinolytic systems, leading to
multiple organ system failure. Obviously, estimation of
PMN elastase is not a diagnostic test for AP but may
indicate severity. Uhl et al. (56) have shown that elastase
levels differentiate edematous from necrotic pancreatitis.
The PMN elastase level is comparable to CRP in predicting
necrosis. Its advantage over CRP is that its peak levels are
reached on day 1 of onset and the levels fall rapidly in
patients with edematous pancreatitis, compared to CRP values, which remain elevated.
Pancreatitis-Associated Protein (PAP)
PAP, an acute phase protein, is secreted from pancreatic
acinar cells (57, 58), especially in AP. It induces extensive
bacterial aggregation and thus may play a role in the prevention of bacterial infection in AP. PAP levels have been
correlated with severity of pancreatitis in rats (59) and
humans (60), suggesting a prognostic role.
Phospholipase A2 and Ribonuclease
Phospholipase A2 and ribonuclease are elevated in AP but
not in healthy individuals. Phospholipase A2 is produced in
the pancreas and also by neutrophil activation. Several studies have also shown it to be a good early marker of severe
pancreatitis (61 64). In a recent study by Mayer et al. (65),
levels of secretory synovial-type phospholipase were significantly higher in patients with infected necrosis than those
with sterile necrosis, and levels of 300 ng/ml on 2 successive days within the first 4 days predicted infected necrosis with a high sensitivity and specificity. Warshaw and
Lee (66) have reported a relationship between serum levels

Evaluation of Laboratory Tests in Acute Pancreatitis

1313

of pancreatic ribonuclease and the need for operative treatment of pancreatic necrosis or abscesses. They found that,
among 24 patients with normal ribonuclease levels, only one
required surgical treatment for abscesses. In contrast, 11 of
13 patients with elevated ribonuclease required surgical
intervention. These relationships need further evaluation in
a large group of patients. The assays are cumbersome and
not currently available for clinical use.
Interleukins
The activation of inflammatory cells that release cytokines
plays an important role in the pathogenesis of the disease.
Various studies have demonstrated that IL-6 and IL-8 peak
within the first 24 h after onset of symptoms and are significantly higher in patients with severe AP (6772). A
study of serum markers in ERCP-induced AP showed that
the earliest peak was of serum IL-8, 12 h after the procedure,
followed by IL-6s peak at 24 h and CRPs peak at 72 h.
Chen and associates (52) have observed that, when compared to serum TNF-, IL-1B, IL-8, and CRP, IL-6 is the
best early predictor (day 1 after admission) of severe AP.
Using a cutoff value of 400 pg/ml, the sensitivity, specificity, and accuracy were 89%, 87%, and 88%, respectively,
on day 1. Furthermore, patients with fatal outcomes showed
the most markedly elevated IL-6 concentrations (25 times
the mean values in severe pancreatitis) on days 1 and 2, and
they remained elevated on day 7. The disadvantage is that
the routine determination of IL-6 is not yet widely available.
A rapid dipstick method for estimation of IL-8 is also under
investigation (72).
In contrast, IL-10 reduces the inflammatory response in
experimental pancreatitis. In humans, Pezzelli and associates (68) have also observed higher levels of IL-10 in the
sera of patients with mild disease.
Tumor Necrosis Factor
The prognostic significance of serum TNF in AP has not
been established, as its release is variable and phasic. deBeaux et al. (73) have shown that the concentration of
soluble TNF receptors is able to differentiate mild, severe,
and fatal attacks of AP. Banks et al. (74) observed no
significant difference between mild and severe AP, whereas
Chen and associates (52) found significantly elevated levels
in severe AP on days 13 but not on days 4 and 7. The role
of TNF assay as a prognostic marker remains unclear.
Other Serum Markers
Preliminary studies indicate serum procalcitonin to be a
valuable marker for the prediction of infected pancreatic
necrosis as well as septic multiorgan failure (75, 76). Several other markers have been evaluated recently to assess the
severity of AP. These include plasma soluble intercellular
adhesion molecule 1 (76, 77), serum levels of extracellular
matrix (78), serum levels of the activation peptide of carboxypeptidase B (79), serum amyloid A (80), and serum
trypsinogen-2 and trypsinogen-2--1-antitrypsin complex
(81). The use of these tests is currently restricted to research

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Yadav et al.

settings, and further studies defining their clinical importance in assessment of severity of AP are awaited.
Clinical Practice Recommendations for Serum Tests of
Severity
Although a host of newer serum markers hold promise for
the future, they are still experimental, used in research
settings, and not widely available. Serum CRP is the best
available serum marker presently to assess the severity of
AP. A cutoff level of 150 mg/L is now accepted as a
proven predictor of severity.

CRITERIA UTILIZING MULTIPLE LABORATORY TESTS

Blood urea nitrogen with glucose levels have been shown to
be helpful in identifying patients with severe AP (82). The
most commonly used criteria for predicting severity are
Ransons criteria (83), which include 11 signs with prognostic significance. The mortality is related to the number of
these signs present: 0.9% with less than three positive prognostic signs, 16% with three or four, 40% with five or six,
and 100% with more than six signs (84). A modification of
Ransons signs as suggested by Osborne et al. (85) is used
in the United Kingdom. They have excluded Hct, base
deficit, and fluid sequestration, but included serum albumin
of 3.2 g/dl as an important criterion of severity.
Acute Physiology and Chronic Health Evaluation
(APACHE-II) uses the worst values of 12 physiological
measurements, age, and previous health status to provide a
general measure of severity of disease (86). The physiological variables considered are temperature, mean arterial
pressure, heart rate, respiratory rate, arterial oxygenation,
arterial pH, serum sodium, serum potassium, serum creatinine, Hct, white blood cell count, and Glasgow Coma Scale.
An APACHE-II score of 8 indicates severe AP. The
advantages of APACHE-II over other prognostic criteria are
objective determination of AP within hours of admission
and the ability to be recalculated daily so as to follow the
course of the disease and response to therapy.

LABORATORY TESTS TO PREDICT THE ETIOLOGY OF AP

The height of amylase or lipase does not predict the etiology
of AP. A reported benefit of estimating serum lipase is that
it might suggest the etiology of AP. Gumaste et al. (87)
found that a lipase/amylase ratio of 2 was suggestive of
acute alcoholic pancreatitis. Several other studies have tried
to determine the utility value of the lipase/amylase ratio
(88 91). Although all studies did not agree that a lipase/
amylase ratio is a precise indicator, most reveal a definite
trendvalues of 3 are highly indicative of acute alcoholic
pancreatitis, whereas low values (12) are more suggestive of gallstone pancreatitis (90). Controversy still exists
with regard to the utility of the ratio in clinical practice. A
recent practice guideline article (25) did not recommend it.
Table 2 summarizes the laboratory tests in AP.

AJG Vol. 97, No. 6, 2002

Table 2. Laboratory Tests in AP

Tests for diagnosis
Serum tests
1. Amylase
2. Isoamylases
3. Macroamylases
4. Lipase
5. Immunoreactive trypsin
6. Elastase
Urine tests
1. Amylase
2. Lipase
Fluid amylase
Tests for severity
Serum tests
1. CRP
2. Interleukins (IL-6, IL-8, etc)
3. Polymorphonuclear elastase
4. PAP
5. Phospholipase
6. Procalcitonin
7. TNF-
8. Ribonuclease
9. Methalbumin
Urine tests
TAPs

Several studies have looked at the utility of liver function

tests in predicting gallstone pancreatitis (9294). According
to a recent meta-analysis (95), an ALT level of 150 U/L
(approximately a 3-fold elevation) has a positive predictive
value of 95% in diagnosing acute gallstone pancreatitis.
However, the sensitivity is only 50%. Bilirubin and ALP
were not found to be as useful as ALT (95).

URINE TESTS
Diagnosis
Although routine use of urinary amylase is not done widely
to evaluate a patient with AP, recently several studies have
reported the use of urinary dipstick tests for screening cases
of AP in the emergency room (96, 97). A dipstick test for
detecting pancreatic amylase in urine by an immunochromatography principle using the monoclonal antibodies specific for pancreatic amylase in initial studies has shown
promising results (97). The test has a high specificity of 97%
and is likely to become useful in the emergency room
setting. Other tests have reported the clinical utility of the
urine trypsinogen-2 dipstick test in AP for screening patients with suspected AP as well as predicting the severity
(98, 99). In a study of 525 consecutive patients presenting to
the emergency room with abdominal pain, the sensitivity
and specificity of diagnosing AP were 96% and 92%, respectively. All nine patients with severe AP were detected
by the dipstick (98).
Severity
Trypsinogen activation peptides (TAPs) are the highly conserved tetra-1-aspartyl-1-lysyl amino terminal peptides re-

AJG June, 2002

Evaluation of Laboratory Tests in Acute Pancreatitis

1315

Table 3. Comparison of Laboratory Tests for AP

Amylase

Lipase

Sensitivity
Specificity
Prediction of severity

67100%*
8598%
None

82100%
82100%
None

Comments

Cheap, widely
available

Cheap, widely
available

Serum CRP
Test for severity
Test for severity
Yes
(150 mg/L at
48 h)
Cheap, widely
available, best
available lab
test for severity

Urinary TAPs

Interleukins (IL-6, IL-8)

Test for severity

Test for severity
Yes
(peak within 1224 h)

Test for severity

Test for severity
Yes
(peak within 1224 h)

Not widely available,

expensive

Experimental

* Poor sensitivity in hyperlipidemic AP, acute or chronic AP due to alcohol, and delayed estimation.
Better than amylase. Lipase is increasingly being recognized as nonspecific.

leased during the activation of trypsinogen to trypsin.

Though normally produced in the intestinal lumen after
activation of trypsinogen by enterokinase, they are not absorbed, because of degradation by enteric oligopeptidases
(100 103). In AP, premature intrapancreatic activation of
trypsinogen leads to the release of TAPs into blood, lymphatics, and peripancreatic tissue, leading to increased concentrations in body fluids. TAPs are liberated within the first
few hours of the onset of AP, and they peak within 1224
h of admission.
Experimental studies done in animals and humans have
found estimation of TAPs to be helpful as a prognostic
marker in differentiating severe from mild AP. Gudgeon et
al. in their study (103) found urinary TAP estimation to be
much better than serum CRP levels. When a urinary concentration of 2 nmol/L was used as a cutoff on admission,
the sensitivity and specificity for predicting severe AP were
80% and 90%. When the highest concentration of TAPs in
the first 24 h was used, the sensitivity and specificity of
urinary TAP levels of 10 ng/ml were 100% and 85% in
predicting severe AP (104).
Neoptolemus and associates (105) in a prospective study
compared levels of urinary TAPs with serum CRP and the
three currently used scoring systems in 172 patients with AP
(35 with severe disease) and 74 controls. Urinary TAP
concentrations differed significantly between mild and severe AP at 24 h and 48 h after onset of symptoms and also
at 24 h and 48 h after admission. CRP concentrations differed significantly at 48 h but not at 24 h. TAPs at 24 h (34
mmol/L) were similar to an APACHE-II score of 8 (0 12
h after admission) with respect to sensitivity (58% vs 58%),
specificity (73% vs 76%), positive predictive value (39% vs
40%), negative predictive value (86% vs 87%), and accuracy (70% vs 72%) (Table 3).

ASCITIC FLUID ANALYSIS

CLINICAL PRACTICE RECOMMENDATIONS. The assay of TAPs for determining severity of AP is appealing as
a single marker that is able to provide accurate severity
prediction within 24 h after onset of symptoms. These
encouraging results should be considered preliminary, and
further studies are needed to establish its role in the evaluation of AP. Presently, TAP assays are not widely available.

It is clear that there is no biochemical test that can be

considered to be a gold standard for the diagnosis or assessment of severity of AP. Amylase and lipase remain important tests in the diagnosis of AP. Lipase, which was initially
thought to be more specific than amylase, has recently been
shown to be almost as nonspecific as amylase. The use of
other tests like P-isoamylase, IRT, elastase, urinary amylase

Early appearance of ascites is seen in over 60% of cases of

severe AP (106). This peritoneal exudate is rich in activated
lipolytic and proteolytic enzymes, vasoactive substances,
and several other proinflammatory mediators. Ascites may
play a role in the transfer of toxic mediators into the systemic circulation or may be a reflection of the locoregional
necrotizing process (106). A peritoneal tap can provide
corroborative evidence of AP by the presence of a high
amylase concentration, especially if sterile fluid is aspirated
(106). The biochemical composition of peritoneal fluid during AP, however, reveals no major differences between the
principal etiological categories of AP (107, 108).
McMahon et al. (109) have shown that volume and color
of peritoneal fluid are indicators of the severity of an attack
of AP. Severe AP is indicated in the presence of one or more
of the following: greater than 20 ml of free peritoneal fluid,
dark-colored free intraperitoneal fluid, and lavage fluid
darker than a pale straw color obtained after peritoneal
lavage with a liter of normal saline. However, peritoneal
lavage is an invasive procedure that is not applicable for
patients with mild disease and contraindicated in patients
with previous scars, obesity, coagulopathy, or difficulty in
catheterization. It is associated with visceral puncture in
0.8% of patients. It is also a poor system for accurate
grading of patients with biliary pancreatitis (108).
CLINICAL PRACTICE RECOMMENDATIONS. Diagnostic peritoneal lavage is an invasive test and a poor system
for grading the severity of AP. It has never been accepted
widely into clinical practice.

RESULTS AND DISCUSSION

1316

Yadav et al.

and lipase, and fluid amylase has no clear role in the evaluation of patients with AP. Urinary TAPs within 1224 h
and serum CRP at 48 h are now considered by many to be
good markers for predicting severity of AP. A host of new
serological markers have been investigated in the last few
years to predict the severity of AP early. Some of them show
promise but have yet to prove their superiority.
Reprint requests and correspondence: C. S. Pitchumoni, M.D.,
M.A.C.G., M.P.H., Professor of Medicine and Preventive & Community Medicine, New York Medical College, Director, Department of Medicine & Chief of GI, Our Lady of Mercy Medical
Center, 600 East 233rd Street, Bronx, NY 10466.
Received Feb. 6, 2001; accepted Jan. 15, 2002.

REFERENCES
1. Agarwal N, Pitchumoni CS, Sivaprasad AV. Evaluating tests
for acute pancreatitis. Am J Gastroenterol 1990;85:356 66.
2. Salt WB, Schenker S. Amylaseits clinical significance: A
review of the literature. Medicine 1976;55:269 89.
3. Steinberg WM, Goldstein SS, Davis ND, et al. Diagnostic
assays in acute pancreatitis. Ann Intern Med 1985;102:576
80.
4. Jacobs ML, Daggett WM, Civetta JM, et al. Acute pancreatitis. Analysis of factors influencing survival. Ann Surg
1977;185:4351.
5. Keim V, Teich N, Fiedler F, et al. A comparison of lipase and
amylase in the diagnosis of acute pancreatitis in patients with
abdominal pain. Pancreas 1998;16:459.
6. Clavien PA, Robert J, Meyer P, et al. Acute pancreatitis and
normoamylasemia. Not an uncommon combination. Ann
Surg 1989;210:614 20.
7. Spechler SJ, Dalton JW, Robbins AH, et al. Prevalence of
normal serum amylase levels in patients with acute alcoholic
pancreatitis. Dig Dis Sci 1983;28:8659.
8. Ventrucci M, Pezzilli A, Naldoni P, et al. Serum pancreatic
enzyme behavior during the course of acute pancreatitis.
Pancreas 1987;2:506 9.
9. Toskes PP. Hyperlipidemic pancreatitis. Gastroenterol Clin
North Am 1990;19:78391.
10. Warshaw AL, Bellini CA, Lesser PB. Inhibition of serum and
urine amylase activity in pancreatitis with hyperlipemia. Ann
Surg 1975;182:72.
11. Mishkin S, Bates J, OHashi J, et al. Possible mechanisms of
normal amylase activity in hyperlipemic pancreatitis. CMAJ
1976;115:1016 9.
12. Webber J, Fromm D. Assessment, diagnosis, and initial treatment. In: Howard J, Yasuo I, Ihse I, Prinz R, eds. Surgical
diseases of the pancreas, 3rd ed. Baltimore: Williams &
Wilkins 1998:20727.
13. Humphries CC, Adams LJ, Eckfeldt JH, et al. Hyperamylasemia in patients with eating disorders. Ann Intern Med
1987;106:50 2.
14. Lott JA. The value of clinical laboratory studies in acute
pancreatitis. Arch Pathol Lab Med 1991;115:3257.
15. Berk JE, Fridhandler L, Webb SF. Does hyperamylasemia in
the drunken alcoholic signify pancreatitis? Am J Gastroenterol 1979;71:557 62.
16. Dutta SK, Douglass W, Smalls UA, et al. Prevalence and
nature of hyperamylasemia in acute alcoholism. Dig Dis Sci
1981;26:136 41.
17. Clavien PA, Burgan S, Moossa AR. Serum enzymes and the

AJG Vol. 97, No. 6, 2002

18.
19.
20.
21.
22.
23.

24.
25.
26.
27.
28.
29.
30.
31.
32.
33.
34.

35.
36.
37.
38.
39.
40.

other laboratory tests in acute pancreatitis. Br J Surg 1989;

76:1234 43.
Warshaw AL, Hawboldt MM. Puzzling persistent hypramylasemia, probably neither pancreatic nor pathologic. Am J
Surg 1988;155:453 6.
Gullo L. Familial pancreatic hyperenzymemia. Pancreas
2000;20:158 60.
Berk JE, Fridhandler J. Hyperamylasemia. Interpretation and
newer approaches to evaluation. Adv Intern Med 1980;26:
253 64.
Thomson HJ, Obekpa PO, Smith AN, et al. Diagnosis of
acute pancreatitis: A proposed sequence of biochemical investigation. Scand J Gastroenterol 1987;22:719 24.
Winslet M, Hall C, London NJ, et al. Relation of diagnostic
serum amylase to aetiology and severity of acute pancreatitis.
Gut 1992;33:982 6.
Lankisch PG, Burchard-Recker IS, Lehrich D. Underestimation of acute pancreatitis: Patients with only a small increase
in amylase/lipase levels can also have or develop severe
acute pancreatitis. Gut 1999;44:542 4.
Williamson RCN. Early assesssment of severity in acute
pancreatitis. Gut 1984;25:13319.
Banks PA. Practice guidelines in acute pancreatitis. Am J
Gastroenterol 1997;92:377 86.
Hiatt JR, Calabria RP, Passaro E, et al. The amylase profile:
A discriminant in biliary and pancreatic disease. Am J Surg
1987;154:490 2.
Tietz NW, Shuey DF. Lipase in serumthe elusive enzyme:
An overview. Clin Chem 1993;39:746 56.
Panteghini M. Lipase. Clin Chem News 1991;17(2):6 7 (review).
Frank B, Gottlieb K. Amylase normal, lipase elevated: Is it
pancreatitis? A case series and review of the literature. Am J
Gastroenterol 1999;94:4639.
Apple F, Benson P, Preese L, et al. Lipase and pancreatic
amylase activities in tissues and in patients with hyperamylasemia. Am J Clin Pathol 1991;96:610 4.
Gumaste VV, Roditis N, Mehta D, et al. Serum lipase levels
in non-pancreatic abdominal pain versus acute pancreatitis.
Am J Gastroenterol 1993;88:20515.
Gottelieb K, Sherman S, Lehman GA, et al. Early recognition
of post-ERCP pancreatitis by clinical assessment and serum
pancreatic enzymes. Am J Gastroenterol 1996;91:15537.
Lott JA, Speicher CE, Nemesanszky E. Is serum amylase an
obsolete test in the diagnosis of acute pancreatitis? Arch
Pathol Lab Med 1985;109:314 5 (editiorial).
Yadav D, Nair S, Norkus EP, et al. Non-specific hyperamylasemia and hyperlipasemia in diabetic ketoacidosis: Incidence and correlation with biochemical abnormalities. Am J
Gastroenterol 2000;95:3123 8.
Heikius B, Niemela S, Lehtola J, et al. Elevated pancreatic
enzymes in inflammatory bowel disease are associated with
extensive disease. Am J Gastroenterol 1999;94:10629.
Tietz NW. Support of the diagnosis of pancreatitis by enzyme
test old problems, new techniques. Clin Chim Acta 1997;
257:8598.
Tetraut GA. Lipase activity in serum measued with Ektachem
is often increased in non-pancreatic disorders. Clin Chem
1991;37:4751.
Chase WC, Barker DE, Russel WL, et al. Serum amylase and
lipase in the evaluation of acute abdominal pain. Am Surg
1996;62:1028 34.
Moossa AR. Diagnostic tests and procedures in acute pancreatitis. N Engl J Med 1984;311:639 43.
Kolars JC, Ellis CJ, Levitt MD. Comparison of serum amylase, pancreatic isoamylase and lipase in patients with hyperamylasemia. Dig Dis Sci 1984;29:289 93.

AJG June, 2002

41. Ventrucci M, Pezzilli A, Naldoni P, et al. A rapid assay for

serum immunoreactive lipase as a screening test for acute
pancreatitis. Pancreas 1986;4:320 3.
42. Dervenis C, Johnson CD, Bassi C, et al. Diagnosis, objective
assessment of severity, and management of acute pancreatitis. Santorini Consensus Conference. Int J Pancreatol 1999;
25:195210.
43. Werner H, Steinberg WM, Pauley C. Strategic use of individual and combined enzyme indicators for acute pancteatitis
analyzed by reciever operator characteristics. Clin Chem
1989;35:96771.
44. Piper-Bigelow C, Strocchi A, Levitt MD. Where does serum
amylase come from and where does it go? Gastroenterol Clin
North Am 1990;19:793 810.
45. Berk JE, Kizu H, Wilding P, et al. Macroamylasemia: A new
recognized cause for elevated serum amylase activity. N Engl
J Med 1967;277:941 6.
46. Imrie CW, King J, Henderson AR. Macroamylasemiasurvey of prevalence in a mixed population. N Engl J Med
1972;287:931.
47. Boyle CE, Fraser CG. Macroamylasemia: How common is
it? Br J Med 1985;291:1389.
48. Malvano A, Marchisio M, Massaglia A, et al. Radioimmunoassay of trypsin-like substance in human serum. Scand J
Gastroenterol Suppl 1980;62:310.
49. Baillargeon JD, Ramagopal V, Tenner SM, et al. Hemoconcentration as an early risk factor for necrotizing pancreatitis.
Am J Gastroenterol 1998;93:2130 4.
50. Brown A, Orav J, Banks PA. Hemoconcentration is an early
marker for organ failure and necrotizing pancreatitis. Pancreas 2000;20:36772.
51. Wilson C, Heads A, Shenkin A, et al. C-reactive protein,
antiproteases, and complement factors as objective markers
of severity in acute pancreatitis. Br J Surg 1989;76:177 81.
52. Chen CC, Wang SS, Lee FY, et al. Proinflammatory cytokines in early assessment of the prognosis of acute pancreatitis. Am J Gastroenterol 1999;94:213 8.
53. Mayer AD, McMahon MJ, Bowen M, et al. C-reactive
protein: An aid to assessment and monitoring of acute pancreatitis. J Clin Pathol 1984;37:20711.
54. Puolakkainen P, Valtonen V, Paananen A, et al. C-reactive
protein (CRP) and serum phospholipase A2 in the assessment
of the severity of acute pancreatitis. Gut 1987;28:764 71.
55. Uhl W, Buchler M, Malfertheiner P, et al. PMN-elastase in
comparison with CRP, anti-proteases, and LDH as indicators
of necrosis in human acute pancreatitis. Pancreas 1991;6:
2539.
56. Uhl W, Buchler M, Malfertheiner P, et al. PMN-elastase: A
new serum marker for the staging of acute pancreatitis.
Digestion 1989;43:176 7.
57. Iovanna J, Orelle B, Keim V, et al. Messenger RNA sequence
and expression of rat pancreatitis associated protein is overexpressed during acute experimental pancreatitis. J Biol
Chem 1991;226:24664 9.
58. Keim V, Iovanna JL, Dagorn JC. The acute phase reaction of
the exocrine pancreas: Gene expression and synthesis of
pancreatitis associated protein. Digestion 1994;35:6572.
59. Keim V, Willemer S, Iovanna JL, et al. Rat pancreatitisassociated protein is expressed in relation to severity of
experimental pancreatitis. Pancreas 1994;9:606 12.
60. Iovanna JL, Kein V, Nordback I, et al. Serum levels of
pancreatitis-associated protein as indicators of the course of
acute pancreatitis. Gastroenterology 1994;106:728 34.
61. Schroder T, Kivilaakso E, Kinnunen PK, et al. Serum phospholipase-A2 in human acute pancreatitis. Scand J Gastroenterol 1980;15:633 6.

Evaluation of Laboratory Tests in Acute Pancreatitis

1317

62. Nevalainen TJ. The role of phospolipase A in acute pancreatitis. Scand J Gastroenterol 1980;15:64150.
63. Buchler M, Malfertheiner P, Schadlich M, et al. Role of
phospholipase-A2 in human acute pancreatitis. Gastroenterology 1989;97:1521 6.
64. Bird NC, Goodman AJ, Johnson AG. Serum phospholipase
A2 activity in acute pancreatitis: An early guide to severity.
Br J Surg 1989;76:7312.
65. Mayer J, Rau B, Grewe M, et al. Secretory phospholipase A2
in patients with infected pancreatic necrosis in acute pancreatitis. Pancreas 1998;17:2727.
66. Warshaw AL, Lee KH. Serum ribonuclease elevation and
pancreatic necrosis in acute pancreatitis. Surgery 1979;86:
22734.
67. Gross V, Andreesen R, Leser HG, et al. Interleukin-8 and
neutrophil activation in acute pancreatitis. Eur J Clin Invest
1992;22:200 3.
68. Pezzelli R, Belli P, Miniero R, et al. Serum interleukin-6,
interleukin-8 and alpha-2 microglobulin in early assessment
of severity of acute pancreatitis. Comparison with C-reactive
protein. Dig Dis Sci 1995;40:2341 8.
69. Leser HG, Gross H, Scheibenbogen C, et al. Elevation of
interleukin-6 concentration precedes acute phase response
and reflects severity in acute pancreatitis. Gastroenterology
1991;101:7825.
70. Viedma JA, Perez-Mateo M, Dominquez JE, et al. Role of
interleukin-6 in acute pancreatitis: Comparison with C-reactive protein and phospholipase A. Gut 1992;33:1264 7.
71. Heath DI, Cruickshank A, Gudgeon M, et al. Role of interleukin-6 in mediating the acute phase protein response and
potential as an early means of severity assessment in acute
pancreatitis. Gut 1993;34:415.
72. Rau B, Steinbach G, Mayer J, et al. The role of interleukin-8
in the severity assessment of septic complication in necrotizing pancreatitis. Digestion 1997;58(suppl 2):11.
73. deBeaux AC, Goldie AS, Ross JA, et al. Serum concentration
of inflammatory mediators related to organ failure with acute
pancreatitis. Br J Surg 1996;83:349 53.
74. Banks RE, Evans SW, Alexander D, et al. Is fatal pancreatitis
a consequence of excessive leukocyte stimulation? The role
of tumor necrosis factor alpha. Cytokine 1991;3:6 12.
75. Rau B, Steinbach G, Gansauge F, et al. The potential role of
procalcitonin and interleukin-8 in the prediction of infected
necrosis in acute pancreatitis. Gut 1997;41:832 40.
76. Mandi Y, Farkas G, Takacs T, et al. Diagnostic relevance of
procalcitonin, IL-6, and sICAM-1 in the prediction of infected necrosis in acute pancreatitis. Int J Pancreatol 2000;
28:4351.
77. Kaufmann P, Demel U, Tilz GP, et al. Time course of plasma
intercellular adhesion molecule-1 (sICAM-1) is related to
severity of acute pancreatitis. Hepatogastroenterology 1999;
46:256571.
78. Lohr M, Hummel F, Martus P, et al. Serum levels of extracellular matrix in acute pancreatitis. Hepatogastroenterology
1999;46:326370.
79. Appelros S, Petersson U, Johnson C, et al. Activation peptide
of carboxypeptidase C and anionic trypsinogen as early predictors of the severity of acute pancreatitis. Br J Surg 2001;
88:216 21.
80. Rau B, Steinbach G, Baumgart K, et al. Serum amyloid A
versus C-reactive protein in acute pancreatitis: Clinical value
of an alternative acute-phase reactant. Crit Care Med 2000;
28:736 42.
81. Hedstrom J, Kemppainen E, Andersen J, et al. A comparison
of serum trypsinogen and trypsin-2-alpha-1-antitrypsin complex with lipase and amylase in the diagnosis and assessment

1318

82.
83.
84.
85.
86.
87.

88.
89.

90.
91.
92.

93.

94.

95.

Yadav et al.

of severity in the early phase of acute pancreatitis. Am J

Gastroenterol 2001;96:424 30.
Fan ST, Choi TK, Lai ECS, et al. Prediction of severity of
acute pancreatitis: An alternative approach. Gut 1989;30:
15915.
Ranson JH, Pasternack BS. Statistical methods for quantifying the severity of clinical acute pancreatitis. J Surg Res
1977;22:79 91.
Ranson JH. Acute pancreatitis. Curr Probl Surg 1979;16:1
84.
Osborne DH, Imrie CW, Carter DC. Biliary surgery in the
same admission for gallstone acute pancreatitis. Br J Surg
1981;68:758 61.
Knaus WA, Draper EA, Wagner DP, et al. APACHE II: A
severity of disease classification system. Crit Care Med 1985;
13:818 29.
Gumaste VV, Dave PB, Weissman D, et al. Lipase/amylase
ratio. A new index that distinguishes acute episodes of alcoholic from non-alcoholic acute pancreatitis. Gastroenterology
1991;101:1361 6.
Sadowski DC, Todd JK, Sutherland LR. Biochemical models
as early predictors of the etiology of acute pancreatitis. Dig
Dis Sci 1993;38:637 43.
Moster SG, Herbsmann D, Kniaz JL, et al. Use of lipase:
amylase (LA) ratio in distinguishing alcoholic versus gallstone causes of acute pancreatitis. Am J Gastroenterol 1993;
88:1536 (abstract).
Tenner SM, Steinberg W. The admission serum lipase:
amylase ratio differentiates alcoholic from non-alcoholic
acute pancreatitis. Am J Gastroenterol 1992;87:1755 8.
Lankisch PG, Petersen M. Lipase/amylase ratio: Not helpful
in the early etiological differentiation of acute pancreatitis. Z
Gastroenterol 1994;32:8 11.
Wang SS, Lin XZ, Tsai YT, et al. Clinical significance of
ultrasonography, computed tomography and biochemical
tests in the rapid diagnosis of gallstone-related pancreatitis. A
prospective study. Pancreas 1988;3:153 8.
Scholmerich J, Gross V, Johannesson T, et al. Detection of
biliary origin of acute pancreatitis: Comparison of laboratory
tests, ultrasound, computed tomography, and ERCP. Dig Dis
Sci 1989;34:830 3.
Ros E, Navarro S, Bru C, et al. Occult microlithiasis in
idiopathic acute pancreatitis: Prevention of relapses by cholecystectomy or ursodeoxycholic acid. Gastroenterology
1991;101:17019.
Tenner S, Dubner H, Steinberg W. Predicting gallstone pancreatitis with laboratory parameters: A meta-analysis. Am J
Gastroenterol 1994;89:1863 6.

AJG Vol. 97, No. 6, 2002

96. Burkitt DS. The rapignost-amylase test in acute pancreatitis.

Br J Surg 1987;74:1063.
97. Hedstrom J, Svens E, Kenkimaki P. Evaluation of new urinary amylase test strip in the diagnosis of acute pancreatitis.
Scand J Clin Lab Invest 1998;58:611 6.
98. Kylanpaa-Back ML, Kemppainen E, Puolakkainen P, et al.
Reliable screening for acute pancreatitis with rapid urine
trypsinogen-2 test strip. Br J Surg 2000;87:49 52.
99. Pezzilli R, Morselli-Labate AM, dAlessandro A, et al. Timecourse and clinical value of the urine trypsinogen-2 dipstick
test in acute pancreatitis. Eur J Gastroenterol Hepatol 2001;
13:269 74.
100. Guy O, Lombardo D, Bartelt DC, et al. Two human trypsinogens. Purification, molecular properties, and n-terminal
sequence. Biochemistry 1978;17:1669 75.
101. Hurley PR, Cook A, Jehanli A, et al. Development of radioimmunoassays for free tetra-L-aspartyl-L-lysine trypsinogen
activation peptides (TAP). J Immunol Methods 1988;111:
195203.
102. Schmidt J, Fernandez-del Castillo C, Rattner DW, et al.
Trypsinogen activation peptides in experimental rat
pancreatitis: Prognostic implications and histopathologic correlates. Gastroenterology 1992;103:1009 16.
103. Gudgeon AM, Heath DI, Hurley P, et al. Trypsinogen activation peptides assay in the early prediction of severity of
acute pancreatitis. Lancet 1990;335:4 8.
104. Tenner S, Fernandez-del Castillo C, Warshaw A, et al. Urinary trypsinogen activation peptide (TAP) predicts severity
in patients with acute pancreatitis. Int J Pancreatol 1997;21:
10510.
105. Neoptolemus JP, Kemppainen EA, Mayer JM, et al. Early
prediction of severity in acute pancreatitis by urinary
trypsinogen activation peptides: A multicenter study. Lancet
2000;355:1955 60.
106. Dugernier T, Laterre PF, Reynaert MS. Astices fluid in
severe acute pancreatitis: From pathophysiology to therapy.
Acta Gastroenterol Belg 2000;63:264 8.
107. Dubick MA, Mayer D, Majumdar APN, et al. Biochemical
studies in peritoneal fluid from patients with acute
pancreatitis: Relationship to etiology. Dig Dis Sci 1987;32:
30512.
108. Corefield AP, Cooper MJ, Williamson RCN, et al. Prediction
of severity in acute pancreatitis: Prospective comparison of
three prognostic indices. Lancet 1985;2:4037.
109. McMahon MJ, Playforth MJ, Pickford IR. A comparative
study of methods for the prediction of severity of attacks of
acute pancreatitis. Br J Surg 1980;67:225.