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42
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Clinical andLaboratory Diagnosis ofChronic Pancreatitis
Georg Beyer1, Markus M. Lerch2, and Julia Mayerle
1
Department of Medicine II, LMU University Hospital, Ludwig- Maximilians- University, Munich, Germany
2
LMU University Hospital, Munich, Germany
1
349
Introduction
For centuries the pancreas was a “terra incognita” hidden
behind the stomach and its pathophysiological role
remained obscure. In 1761 Jean- Baptista Morgagni
described the first case of chronic pancreatitis in his
book De sedibus et causis morborum and it took a further
60 years until Kuntzmann was able to connect fatty stool
to diseases of the pancreas. Even in the twenty- first century the time interval between the onset of symptoms
and the diagnosis of chronic pancreatitis is unacceptably
long and this is mainly caused by the fact that routine
blood tests are usually not helpful in diagnosing chronic
pancreatitis and that clinical symptoms are often nonspecific. The modern clinical concept of clinical chemistry for pancreatic diseases began in 1929 with the
introduction of serum amylase (diastase) measurements[1]. Thereafter Comfort and coworkers[2] combined clinical observations, surgical findings, and
autopsy studies to characterize chronic pancreatitis and
first reported a chronic relapsing course of the disease.
They also commented on its frequent association with
longstanding alcohol intake, its common onset in the
third and fourth decade of life, and the typical complications of the disease such as exocrine and endocrine pancreatic insufficiency.
Clinical Presentation
With a global incidence of 34 (CI 23–49), a prevalence of
13.5 to 52.4 per 100,000 population and a frequency of
0.04% to 5% among all autopsies, chronic pancreatitis
represents a rather common disorder of the gastrointestinal tract[3,4]. Chronic pancreatitis also accounts for a
substantial morbidity and healthcare costs. Although
most patients with chronic pancreatitis are treated as
outpatients, in 2017 there were almost 20,000 (ICD- 10:
K86) hospital admissions for chronic pancreatitis in
Germany alone (Federal Statistics Office). This does not
include those patients who were coded as having acute
pancreatitis, including those reporting an acute episode
of chronic pancreatitis (55,221 cases). Evaluating records
from the United States, United Kingdom, the
Netherlands, and Finland confirmed an increasing number of annual hospital admissions amounting to a 30%
increase within 6 years [5]. This substantiates the high
socioeconomic significance of the disease. Mortality
from chronic pancreatitis is reported to be 12.8 – 19.8 %,
over a mean observation period of 6.3 – 9.8 years[6–8].
Total mortality in the same studies was reported to be
28.8 – 35 %. Continued alcohol consumption results in a
significantly reduced survival rate. The number of
patients who leave the workforce and abandon gainful
employment due to prolonged illness or continued alcohol consumption, or become disabled and are forced to
retire prematurely during the course of the disease
amounts to 40 %. The 10- year survival rate is 70 % and the
20- year survival rate is 45 % in comparison with 93 % and
65 %, respectively, for an age- adjusted cohort[9].
Investigating the time interval between the onset of
symptoms and the diagnosis of chronic pancreatitis a
median interval of 30–55months was reported in alcoholics[10,11]. In nonalcoholics the diagnosis was even
more delayed (median 81 months) and frequently only
established if complications of the disease such as pseudocysts or gastric outlet obstruction occurred. The
major reason for this delay lies in the natural course of
the disease. The clinical presentation of patients with
chronic pancreatitis is highly dependent on the stage of
The Pancreas: An Integrated Textbook of Basic Science, Medicine, and Surgery, Fourth Edition. Edited by Hans G. Beger, Markus W. Büchler,
RalphH. Hruban, Julia Mayerle, John P. Neoptolemos, Tooru Shimosegawa, Andrew L. Warshaw, David C. Whitcomb, and Yupei Zhao.
© 2023 John Wiley & Sons Ltd. Published 2023 by John Wiley & Sons Ltd.
Companion website: www.wiley.com/go/beger/thepancreas4e
Clinical andLaboratory Diagnosis ofChronic Pancreatitis
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350
the disease. It varies between severely ill patients with
symptoms of an acute abdomen to slowly progressing
cachexia. Often the first signs of the disease which
prompt the patient to seek medical attention are belt- like
abdominal pain that frequently radiates to the back, loss
of body weight (in 80%), and steatorrhea (in less than
50%)[12].
Several attempts have been undertaken to establish
histological and morphological criteria that clearly
define chronic pancreatitis. Unfortunately an exact correlation between clinical symptoms, morphological
signs, and histological criteria is still not at hand.
Etiology
In Western countries alcohol consumption is assumed to
be the leading cause (42% to 68%) of chronic pancreatitis [13]. The prevalence of chronic pancreatitis clearly
correlates with the alcohol consumption in a given
population[14].
It is reported that 24.1% of all patients suffering from
acute pancreatitis will progress to chronic pancreatitis[15]. Of those, 48.2% have alcoholic pancreatitis and
smoking was identified as the only independent but
dose- dependent risk factor for disease progression[16].
With regard to the etiology of chronic pancreatitis, more
recent studies suggest that in addition to alcohol consumption smoking increases the risk and can independently cause chronic pancreatitis[17].
The second most common form of chronic pancreatitis (25%), as of today, is so- called idiopathic
pancreatitis[18,19]. Patients without an identifiable risk
factor for chronic pancreatitis are classified as having
idiopathic pancreatitis. This group is constantly decreasing since Comfort and Steinberg reported in 1952 an
inherited form of chronic pancreatitis that follows an
autosomal dominant inheritance pattern and knowledge about genetic susceptibility factors is accumulating [2]. Hereditary pancreatitis represents a genetic
disorder closely associated with mutations in the cationic trypsinogen gene and presents with a disease penetrance of ≈80%[20]. Shortly after the identification of
mutations in the trypsinogen gene associated with
chronic pancreatitis another important observation was
made by Witt etal. [21]. They found mutations in the
SPINK-
trypsin inhibitor, PSTI) to be associated with idiopathic
chronic pancreatitis in children. SPINK- 1 mutations can
be frequently detected in patients who do not present
with a family history of pancreatitis and are devoid of
classical risk factors for chronic pancreatitis[22,23].
with an estimated incidence of 1 : 2500 characterized by
1 gene (encoding the pancreatic secretory
Cystic fibrosis is an autosomal- recessive disorder
pancreatic exocrine insufficiency and chronic pulmonary disease. The extent to which the pancreas is
affected varies between a complete loss of exocrine and
endocrine function to clinically normal pancreatic
function. Recurrent episodes of pancreatitis occur in
1–2% of all patients with cystic fibrosis who have normal exocrine pancreatic function and much more rarely
in patients with exocrine pancreatic insufficiency. That
means that CFTR changes that would not cause cystic
fibrosis still confer a twice increased risk of developing
pancreatitis.
Metabolic disorders associated with hypertriglyceridemia above 1000 mg/dL can be responsible for the development of recurrent episodes of pancreatitis [24], but
even lower triglyceride levels pose a significant risk[25].
In addition to dietary restrictions, fibrates, and rescue
treatments by lipidapheresis and glucose/insulin infusion
to lower triglyceride levels, the antisense oligonucleotide
volanesorsen has been approved for the treatment of
familial chylomicronemia syndrome, a genetic disorder
leading to lipoprotein lipase deficiency resulting in severe
hypertriglyceridemia. In a prospective, randomized openlabel trial the risk for developing episodes of pancreatitis
was markedly reduced in the treatment group compared
to placebo, although the trial was not powered for this
endpoint[26]. In a few cases chronic calcifying pancreatitis has been reported due to hypercalcemia in patients
with untreated hyperparathyroidism. The underlying
mechanism of hyperparathyroidism- associated pancreatitis is most likely related to the established role of calcium
in the premature, intracellular activation of digestive
proteases[27].
Pain
Pain is the most commonly encountered symptom in
chronic pancreatitis (80–95% of patients)[28]. Up to 50%
of patients with chronic alcoholic pancreatitis may suffer
from chronic pain, while the remaining portion presents
with intermittent attacks followed by painor have never experienced severe pain due to pancreatitis [19,29]. Most patients report continual, numb pain
lasting for more than 24 hours and 68% report epigastric
pain (Fig. 42.1). Pain, which can radiate to the back is
reported in 39%, to the left upper quadrant in 50%, and
to the right upper quadrant in 32%. About 6% of patients
feel their pain radiating between the shoulders. In general, patients with abdominal pain take a “jackknife”
posture to relax abdominal musculature affected by peritonitis. In chronic alcoholic pancreatitis a relationship
between alcohol ingestion and recurrent pain has been
described. Pain often begins between 12 and 48 hours
after ceasing alcohol intake.
free intervals
75
100
125
Fecal fat in % of normal
Lipase secretion, % of normal
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50
Endocrine Insufficiency 351
Figure42.1 Erythema ab igne in a female patient aged 45 years
suffering from chronic alcoholic pancreatitis.
Malabsorption, Weight Loss
Fat excretion of patients with pancreatic steatorrhea frequently exceeds that of patients with other causes of
steatorrhea. Leaking oily stool from the anus is virtually
pathognomonic of exocrine pancreatic insufficiency. In
general, weight loss is a cardinal symptom of pancreatic
exocrine insufficiency with steatorrhea whereas hypoproteinemia or malabsorption of the fat- soluble vitamins
is less common. So far there have only been a few publications that have reported decreased bone mineral density, but no comparison to an agecohort was included[30,31]. Overt steatorrhea occurs in
approximately 30% of patients with chronic calcific
pancreatitis.
With rare exceptions, steatorrhea and azotorrhea
(excessive discharge of nitrogenous substances in the
feces or urine) only occur when the reduction in lipase
and protease secretion, respectively, surpasses 90%[32,33]
(Fig.42.2).
In alcoholic chronic pancreatitis it will usually take 10
to 20 years until severe exocrine insufficiency develops,
but according to DiMagno and coworkers lipase secretion will decrease more rapidly than protease secretion.
In decompensated chronic pancreatitis with less than
5%of the normal enzyme output, about 40% of nutrients
matched control
25
0
0255075 100
Figure42.2 The graph illustrates the reduction in lipase secretion,
which is paralleled by an increase in fecal fat. With rare exceptions,
steatorrhea and azotorrhea only occur if there is greater than 90%
reduction in pancreatic lipase and trypsin secretion. Source:
Adapted from [39].
after ref. 56
normal secretion
from a readily digestible low caloric meal are malabsorbed and enter the colon.
Endocrine Insufficiency
More rarely patients seek medical attention because they
develop diabetes mellitus with a loss of endocrine function or cachexia as the initial symptoms of chronic pancreatitis. A history of diarrhea with recent onset of
diabetes mellitus should always raise the suspicion of
chronic pancreatitis as the underlying cause. The symptoms of diabetes “of other specific types” according to
the WHO classification system released in 2003 (e.g.,
loss of insulin production due to diseases of the exocrine
pancreas) are similar to those of diabetes mellitus of
other causes. Overall 45% of the patients with chronic
pancreatitis suffer from overt diabetes. The cause of
chronic pancreatitis bears no relationship to the subsequent likelihood of developing diabetes, but it does seem
to influence the time lag between onset of pancreatitis
and onset of diabetes. Alcoholics show symptoms of
endocrine insufficiency earlier than nonalcoholics [7].
Diabetes mellitus is also an independent predictor of
mortality in patients with chronic pancreatitis. The
underlying pathophysiology of diabetes in chronic pancreatitis is the loss of insulinbined with a peripheral and hepatic insulin resistance.
Oral antidiabetics and especially metformin might therefore have a role in the treatment of these patients but
control of blood sugar levels should be achieved with
exogenous insulin supplementation.
secreting cells often com-
Clinical andLaboratory Diagnosis ofChronic Pancreatitis
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352
Jaundice
In 10–40% of cases with chronic pancreatitis a benign
dominant stenosis of the common bile duct develops due
to inflammation of the pancreatic head or due to pancreatic pseudocysts or phlegmons, all of which require
either endoscopic or surgical intervention. An asymptomatic increase in alkaline phosphatase is the most common laboratory manifestation of a stenosis of the
common bile duct secondary to chronic pancreatitis.
Jaundice may develop later. However, a raised alkaline
phosphatase or increased bilirubin alone does not always
point to extrahepatic cholestasis but might be a symptom of parenchymal liver damage caused by hepatitis,
steatosis, or even liver cirrhosis. Endoscopic intervention is clinically indicated if the patient presents with
jaundice or cholangitis and in order to prevent secondary biliary cirrhosis, whereas surgery is indicated, if a
malignant cause for jaundice cannot be excluded.
Laboratory Diagnosis
Even after two centuries of pancreatic research a diagnostic serum marker for chronic pancreatitis is not available. Usually the diagnosis is made by a combination of
imaging procedures such as ultrasound, endoscopic
ultrasound, computed tomography (CT) or magnetic
resonance imaging (MRI), or MRCP in combination with
exocrine and endocrine function tests.
Serum Tests forthe Diagnosis andEtiological
Characterization ofChronic Pancreatitis
The simplest, noninvasive tests would be to measure
exocrine pancreatic enzymes or hormones in fasting
blood samples. Total serum amylase, as opposed to pancreatic isoamylase or salivary isoamylase, has been measured routinely since 1929, but it is of little use for the
diagnosis of chronic pancreatitis. Since amylase secretion into the gut decreases in chronic pancreatitis it has
been hypothesized that low serum pancreatic amylase
could be used to diagnose chronic pancreatitis.
Unfortunately, pancreatic isoamylase is completely normal in many patients with mild to moderate chronic pancreatitis and the sensitivity was reported to be only 60%
with a variation between 12% and 100 % depending on
the severity of the disease[34]. The same problems apply
to the measurement of lipase and trypsin. Therefore
pancreatic serum enzyme testing lacks diagnostic accuracy as well as specificity.
Provocation tests, in which serum levels of pancreatic
enzymes are measured after stimulation of pancreatic
secretion by a secretagogues or parasympathomimetics,
have been found to be rather insensitive, nonspecific,
burdened with great interindividual ranges and therefore
just as unreliable as markers for chronic pancreatitis. At
most they are abnormal in 25% of patients suffering from
chronic pancreatitis and at least the same proportion of
healthy volunteers show abnormal test results[35,36].
A promising approach to diagnosing chronic pancreatitis by means of a blood test comes from the use of a
multitude of markers measured on a common platform,
called biomarker signature. In a three- tiered pro-
a sospective discovery and validation design, Adam and
Beyer et al. described a multivariable prediction model
based on blood plasma and serum metabolomics. The
signature is comprised of eight metabolites measured on
GC- MS and LC- MS/MS platforms and pancreatitis subjects were distinguished from non- pancreas disease control subjects with an AUC of 0.85 (95% CI 0.81–0.89) in
EDTA- plasma or 0.87 (95% CI 0.81–0.95) in serum[37].
Similarly, a protein- based signature unique for chronic
pancreatitis was identified by group from Stanford using
the Luminex® assay[38].
Pancreatic Exocrine Function Tests
Tests for exocrine and endocrine pancreatic function serve
as a second line of diagnostic tools for chronic pancreatitis.
Reduced exocrine function can precede overt morphological changes and therefore the sensitivity to detect early
changes is higher for exocrine pancreatic function tests
than for imaging studies. These patients have exocrine
pancreatic insufficiency because enzymes and chime do
not mix appropriately and their fat digestion is accordingly
impaired. However, excreted enzymes, for example elastase
or chymotrypsin in stool, will appear normal.
Several tests for exocrine pancreatic function are now
well established in the diagnostic workup of patients
with suspected chronic pancreatitis. Assays can be
divided into direct and indirect methods depending on
the technique used for determining enzyme output (via
duodenal tube or indirectly). When pancreatic function
is measured directly the stimulated output of enzymes
and bicarbonate into the small intestinal lumen is collected via a nasoduodenal tube and then quantitated.
Indirect methods detect a decreased amount of pancreatic enzymes in stool or serum or, alternatively, evaluate
the digestion of synthetic substrates by pancreatic
enzymes, which also indicate impaired exocrine function
when reduced (Table42.1). The disadvantage of indirect
tests for pancreatic function is that they cannot distinguish between structural or functional abnormalities.
The situation after gastrectomy can serve as a good
example of when an impaired synchrony between
pancreatic secretion and the gastrointestinal passage of
Pancreatic Exocrine Function Tests 353
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Table42.1 Direct andindirect pancreatic function tests.
Pancreatic function test
Direct
Indirect Serum tests:
● Secretin–cholecystokinin test
● Endoscopic secretin test
● Pancreolauryl test
● NBT- PABA test (commercially discontinued)
Fecal tests:
● Fecal elastase
● Chymotrypsin
● Stool weight
● Fecal fat quantification
food will signal exocrine insufficiency on pancreatic
function tests without any structural damage to the pancreas (pancreatico- cibale asynchrony)[39].
Direct Pancreatic Function Tests
Secretin–Cholecystokinin Test
Pancreatic enzyme activity as well as bicarbonate concentration are measured in the duodenal juice after stimulation with the enterohormones secretin (1 CU/kg KG
i.v.) and cholecystokinin (CCK; 25–100 ng/kg KG). The
secretin–cholecystokinin test was the gold standard for
pancreatic function testing. Its overall sensitivity and
specificity is 90%. The combined secretin–CCK test is no
longer used since pharmaceutical CCK preparations for
human use are no longer marketed (at least not in most
countries). Some authors used a standardized test meal
(Lund test) rather than hormone stimulation of the exocrine pancreas but this more “physiological” approach is
ultimately less sensitive in detecting early functional
changes and bicarbonate cannot be measured in the collected chyme. As early as 1982 Gregg suggested a new
method to determine exocrine pancreatic function by
collecting pancreatic juice after intravenous secretin
stimulation during ERP[40]. Until 2003no larger series
of this promising approach had been conducted until
DiMagno and coworkers presented a modified version of
the endoscopic pancreatic function test investigating 412
subjects. The overall accuracy of the endoscopic secretin
test was 79% with positive and negative predictive values
of 73% and 85%, respectively [41]. One possibility to
overcome the limitations of invasive function testing
might be secretin- stimulated MRI. Intravenous application of secretin causes the rapid washout of bicarbonaterich fluid from the exocrine pancreas which can be
quantified semiquantitatively but is significantly reduced
in patients with impaired exocrine function. Sensitivity
of secretin- stimulated MRI was calculated to be 69%
while the specificity was 90%. As MRI is becoming an
alternative to CT scan examination for the diagnosis of
chronic pancreatitis, secretin- MRCP could become a
valuable diagnostic tool[42,43].
Noninvasive Pancreatic Function Tests
Fecal Elastase- 1
Pancreatic elastase accounts for 6% of protein in pancreatic juice. Compared to other serine proteases this
enzyme is highly stable during its passage through the
gut and can be detected with a five- to sixfold concentration in stool (median concentration of 1200 μg/g). Fecal
elastase is measured using an enzyme- linked immunoassay (ELISA) and there are human- specific polyclonal and
monoclonal test kits without cross- reactivity commercially available. It is therefore not necessary for the
patient to discontinue enzyme supplementation treatment because it would potentially contain traces of pork
elastase. The overall sensitivity of fecal elastase testing is
63% for mild exocrine insufficiency and rises to 100% for
severe exocrine insufficiency if compared to the gold
standard of the secretin–cholecystokinin test [44].
Biochemically the elastase 1 assay is a misnomer since
the human pancreas expresses elastase 2 and 3 isoforms
but not elastase 1 isoform known only from pigs.
About 5% of chymotrypsin secreted into the duodenum can be recovered enzymatically active in the feces
and measured by a colorimetric enzyme reaction
employing the substrate N-
glutaryl- - phenylalanine- p-
nitroanilide (GNPNA). Sensitivity and specificity is
regarded to be equal or lower compared to fecal elastase
but false negative results occur in 4% of patients with
severe exocrine insufficiency, 15–18% of patients with
moderate exocrine insufficiency, and 25–40% of patients
with mild pancreatic insufficiency[44,45].
Another noninvasive approach to evaluate pancreatic
exocrine insufficiency is the assessment of CO2 exhalation after digestion of 13 labelled synthetic substrates
such as mixed triglyceride, triolein, and hiolein, which
are enzymatically cleaved by pancreatic enzymes in the
duodenum, and the 13 CO2 component, which is rapidly
resorbed on can therefore be detected in exhaled breath
over time[46]. In patients with severe exocrine insufficiency sensitivity of the detection of mixed triglycerides
is 92% to 100%, but in patients suffering from mild
impairment of exocrine function sensitivity it is reduced
to 46% [47]. However, in addition to the detection of
pancreatic insufficiency these tests can be used for clinical workup of chronic diarrhea or to monitor the efficacy
of enzyme supplementation[48].
Fecal fat quantification by the classical van de Kamer
(alcohol extraction) technique is the standard test to
determine steatorrhea as a characteristic symptom of
Clinical andLaboratory Diagnosis ofChronic Pancreatitis
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354
reduced exocrine function. After a 90% loss of exocrine
function fat excretion in stool significantly increases as
a sign of fat maldigestion. A mild or intermediate
impairment of exocrine function is usually clinically
compensated for. The van de Kamer test has fallen out
of favor with patients, nurses, and technicians because
it requires extensive handling of large amounts of
smelly stool.
Evaluation ofEndocrine Function
Overt diabetes occurs in approximately 20% of patients
suffering from alcoholic chronic pancreatitis 6 years after
disease onset. Ten years after disease onset about 50% of
alcoholic pancreatitis patients display signs of impaired
glucose metabolism with diminished insulin production[49]. Pancreatic endocrine function should be evaluated by measuring HbA1c, fasted glucose or by means of
an oral glucose tolerance test according to the guidelines
of the WHO for the diagnosis of diabetes mellitus. Type
3c diabetes mellitus on the background of CP can be diagnosed if exocrine insufficiency is also present and type 1
diabetes and insulin resistance are unlikely[50].
Genetic Testing
In addition to an evaluation of exocrine and endocrine
function considerable attention is now paid to the etiology of the disease. Recent results from molecular and
genetic studies suggest that a significant number of
patients with chronic pancreatitis suffer from a genetically determined or inherited disease. This is mainly true
for patients who were formerly classified as suffering
from idiopathic pancreatitis, for patients with an onset of
the disease before the age of 25, or those with a positive
family history for chronic pancreatitis or pancreatic cancer. Patients who suffer from chronic pancreatitis due to
mutations in the cationic trypsinogen gene are burdened
with a 70-
to 140- fold increased risk to develop pancreatic
Table42.2 Implications for genetic testing.
Indications for genetic testing in idiopathic or hereditary
pancreatitis
● Recurrent (2 or more) episodes of acute pancreatitis without
identifyable cause or etiology,
or
● Idiopathic chronic pancreatitis– especially in children and
young adults under the age of 25 years,
or
● Pancreatitis in a patients with a positive family history of
pancreatitis (one or more first-
or second- degree relatives)
cancer, particularly if they smoke. Whether, this is also
true for patients who carry SPINK-
1 or CFTR mutations
needs to be determined. Genetic testing for the most
common and clinically relevant trypsinogen gene mutations (N29I and R122H or R122C) can be recommended
for chronic pancreatitis patients who have first- degree
relatives suffering from pancreatitis or pancreatic cancer,
for patients with chronic pancreatitis or recurrent bouts
of acute pancreatitis before the age of 25 years and no
identifiable risk factor[3]. Genetic testing for clinically
unaffected relatives is not indicated and should only be
performed within Ethics Committee approved research
protocols. A much more detailed analysis of the genetic
risk factors of pancreatitis is found in other chapters of
this volume (Table42.2).
In conclusion, even in the twenty- first century the
diagnosis of chronic pancreatitis is made by a combination of clinical symptoms, imaging procedures such as
ultrasound, EUS, CT, and MRCP, and exocrine and
endocrine function tests. Therapy is restricted to symptom control for the lack of a causal treatment strategy
and the time point from first symptoms to diagnosis has
not been significantly shortened during the last 15 years.
Biomarkers or tests are urgently needed but currently
not available.
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43
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Abdominal Imaging forthe Diagnosis ofChronic Pancreatitis
Atsushi Irisawa and Akira Yamamiya
Department of Gastroenterology, Dokkyo Medical University School of Medicine, Tochigi, Japan
357
Introduction
In 2016, a mechanistic definition for progression of chronic
pancreatitis (CP) was proposed [1], with defined conditions of early, established, and end- stage CP. Regarding the
diagnoses of the last two conditions (definite CP), they are
easily diagnosed with identified parenchymal findings such
as parenchymal loss (glandular atrophy), chronic inflammation, and fibrosis of the pancreas, in addition to ductal
findings such as beading, dilated side- branch radicals,
enlargement of the main pancreatic duct (MPD), and dystrophic intraductal calcifications. Diagnostic imaging
modalities include transabdominal ultrasonography (US),
endoscopic ultrasonography (EUS), computed tomography (CT), magnetic resonance imaging/cholangiopancreatography (MRI/MRCP), and endoscopic retrograde
cholangiopancreatography (ERCP)[2,3]. Furthermore, for
the diagnosis of early CP, EUS plays a major role in elucidating subtle changes in the pancreatic parenchyma[4–6].
Although some guidelines for CP recommend CT or MRI
for the first- line diagnosis of CP and either test should be
the first choice for the diagnosis of CP[7,8], this chapter
also describes the significance of minimally invasive tests
such as US and plain abdominal radiography.
Transabdominal Ultrasonography
The simplest and least invasive imaging modality is US,
which is regarded as the first imaging procedure when a
patient has symptoms that suggest CP. Nevertheless, it
must be understood as a limitation that, because of its
low accuracy, US is useful only for the diagnosis of
advanced CP [9]. A definite CP diagnosis based on US
images is made when US shows a pancreatic duct stone,
multiple or diffuse pancreatic calcifications, or obvious
deformation of the pancreas with irregular dilation of the
pancreatic duct [5] (Fig. 43.1). However, because a CP
diagnosis based on US is susceptible to the effects of gastrointestinal tract fats and gas, its sensitivity is not high:
48–83%[10,11]. Consequently, some cases require other
imaging procedures for CP diagnosis. It is also noteworthy that the usefulness of US for diagnosing early CP has
not been established.
Recently, the performance of US-
based CP diagnosis
has been improved by the combined use of US elastography, which measures pancreatic stiffness[12]. US elastography, a new diagnostic tool, measures tissue elasticity
(stiffness) by evaluating distortion and waves occurring
after the addition of the external vibration energy to the
tissue through manual compression and heartbeat. The
pancreatic stiffness that is measured based on the shear
wave elastography has been reported as correlated with
CP progression[13].
Plain Abdominal Radiography
Plain abdominal radiography, a noninvasive and simple
modality, can be used to diagnose radiopaque pancreatic calculus. Furthermore, it offers superior costeffectiveness for the follow- up of patients with CP with
evidence of a stone (Fig.43.2) and those who experience
a stone for the first time. The frontal view of the abdominal radiograph has presented difficulty for independently
detecting pancreatic stones in some cases. Consequently,
three- view abdominal radiography (i.e., frontal, left, and
right views) has been adopted to improve this process[14–16]. The proportion of pancreatic calcifications
in patients with CP is estimated as 17–60.8%; few patients
The Pancreas: An Integrated Textbook of Basic Science, Medicine, and Surgery, Fourth Edition. Edited by Hans G. Beger, Markus W. Büchler,
RalphH. Hruban, Julia Mayerle, John P. Neoptolemos, Tooru Shimosegawa, Andrew L. Warshaw, David C. Whitcomb, and Yupei Zhao.
© 2023 John Wiley & Sons Ltd. Published 2023 by John Wiley & Sons Ltd.
Companion website: www.wiley.com/go/beger/thepancreas4e
Abdominal Imaging forthe Diagnosis ofChronic Pancreatitis
(a) (b)
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358
Figure43.1 Transabdominal ultrasound images of the definite chronic pancreatitis (a and b). Both images of transabdominal ultrasound
show multiple stones in the dilated pancreatic duct with atrophic parenchyma.
Figure43.2 Plain abdominal radiography in patient with definite
chronic pancreatitis. A pancreatic stone is seen (arrow).
are diagnosed with CP based only on abdominal radiography findings[17,18]. However, a diagnosis of noncalcified CP using this modality is difficult to reach.
Computed Tomography
Cross- sectional imaging is the most commonly used
method to establish a diagnosis of CP. Actually, CT is a
highly objective and minimally invasive imaging test.
Furthermore, gastrointestinal fats and gas have little effect
on the diagnostic performance of CT. A study in which
several radiologists read CT images of 39 patients with
CP based on the Cambridge classification and for which
their interobserver variations were evaluated showed
high interobserver reliability, indicating limited variation
among CP diagnoses [19]. Therefore, CT is an excellent
method for visualizing pancreatic calcifications/stones. It
can also visualize apparent pancreatic alterations that
show dilatation of the pancreatic duct with an uneven and
irregular outline, which are findings for probable CP diagnosis. A systematic review that compared different imaging procedures in the diagnostic performance for CP
showed excellent diagnostic performance of abdominal
CT, with sensitivity of 75% (95% confidence interval [CI]:
66–83%) and specificity of 91% (95% CI: 81–96%) [2].
Other studies have also shown high diagnostic performance of abdominal CT for CP diagnosis, with sensitivity
of 74–91% and specificity of 78–85%[20,21]. However, it
should be understood that the pancreatic duct branches
are poorly visualized on CT compared with MRCP or
ERCP in some cases. Furthermore, the diagnosis of CP in
older adults should be treated with caution, given that calcifications might be associated with other diseases in this
population. Recently, the usefulness of virtua1 CT pancreatoscopy has been reported [22]. This modality has
been shown to correlate closely with ERCP imaging.
Actually, CT has no diagnostic significance for early CP.
Furthermore, all imaging must be performed using a
multidetector helical CT scanner[23], from the perspective that CP entails a high risk of carcinogenesis.
The classical CT findings in CP are dilatation of the
pancreatic duct, pancreatic calcifications, and parenchymal atrophy (Fig.43.3). Other CT findings include MPD
dilatation and dilated secondary radicals. The MPD is
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