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Chapter 6
SAGES Manual: Chronic Pancreatitis–
Classication andMedical Management
EmilyHensler andSubhashiniAyloo
Classication ofChronic Pancreatitis
Chronic pancreatitis remains a signicant challenge for medical practitioners
because of its heterogeneity in clinical course and progression among patients [1].
Unlike acute pancreatitis, which has well-established systems for classication and
severity scoring (e.g., the Atlanta classication [2], the Glasgow criteria [3],
Ranson’s criteria [4], and the APACHE II score [5]), no widely accepted and utilized system exists for the classication of chronic pancreatitis. Several classication systems have been proposed, but no single system has become standard in the
management of this disease process. In addition, the majority of proposed classication systems lack rigorous prospective multi-institutional validation [1]. Many of
the proposed classication systems are also less applicable in clinical practice
owing to their focus on radiologic morphology or to the complexity of the classication system itself. Here, we review the Marseille, Cambridge, Rosemont,
TIGAR-O, M-ANNHEIM, ABC, Manchester, Heidelberg, and Chronic Pancreatitis
Prognosis Score (COPPS) classication systems and discuss the strengths and limitations of these systems.
E. Hensler · S. Ayloo (*)
Department of Surgery, Warren Alpert Medical School of Brown University,
Providence, RI, USA
e-mail: ehensler@lifespan.org
Switzerland AG 2025
E. P. Ceppa et al. (eds.), The SAGES Manual of Evolving Techniques in
Pancreatic Surgery, https://doi.org/10.1007/978-3-031-78409-5_6
99© The Author(s), under exclusive license to Springer Nature
100
E. Hensler and S. Ayloo
Marseille Classication
The initial Marseille conference on pancreatitis classication occurred in 1963, and
the group classied pancreatitis into four categories: acute, acute relapsing, chronic
relapsing, and chronic [6]. This classication was then revised at the Second
International Symposium on the Classication of Pancreatitis in 1984 to eliminate
the relapsing acute and chronic relapsing subcategories because of the difculty of
accurately differentiating between the two. This consensus group also differentiated
acute pancreatitis from chronic pancreatitis based on clinical and morphological
criteria, with the caveat that clinical presentation and morphological changes may
not correlate in these patients.
The authors of the 1984 Marseille classication stated that acute pancreatitis
presents clinically as acute attacks of abdominal pain associated with elevations in
serum pancreatic enzymes, occurring either as an isolated episode or as recurrent
attacks over time [6]. These attacks can lead to end organ damage and death, but
patients typically recover without lasting morbidity or progression to chronic pancreatitis. The authors also describe a spectrum of disease, from mild acute pancreatitis, characterized by interstitial edema and some fat necrosis but typically without
necrosis of the parenchyma, to severe acute pancreatitis, characterized by more
extensive fat necrosis within the pancreas and surrounding tissues, necrosis of the
pancreatic parenchyma, and even hemorrhage.
Chronic pancreatitis, in comparison, is often dened by persistent pain with or
without evidence of endocrine or exocrine dysfunction (diabetes or steatorrhea,
respectively). The morphologic changes in patients with chronic pancreatitis include
complications such as pseudocyst formation, ductal dilation, and permanent scarring, which can lead to loss of functional pancreatic parenchyma. The authors break
down classication of chronic pancreatitis based on these morphological changes
(Table6.1) with an additional category for obstructive chronic pancreatitis, which
they describe as being caused by occlusion of the major duct by scarring or tumors,
but rarely stones. Occlusion of the major duct leads to parenchymal atrophy throughout the pancreas as well as brosis—these changes often improve with resolution of
Table 6.1 Summary of the Marseille classication [6]
Acute pancreatitis Chronic pancreatitis
Description Acute episode of pain + elevated
Morphologic
changes
enzymes, ± temporary pancreatic
dysfunction, temporary morphologic
changes
1. Mild: fat necrosis and edema, no
parenchymal necrosis
2. Severe: fat necrosis, parenchymal
necrosis, hemorrhage
Recurrent pain with morphologic
changes, ± pancreatic dysfunction
1. Focal parenchymal necrosis
2. Segmental/diffuse parenchymal
brosis
3. ± Pancreatic calculi
4. Obstructive: occluded duct leading
to ductal dilation, parenchymal
atrophy, diffuse brosis
6 SAGES Manual: Chronic Pancreatitis–Classication andMedical Management
the obstruction. Overall, this early classication system relies heavily on morphological changes to the pancreas, which the authors admit do not always correlate to
a patient’s clinical presentation and disease course. This limits the applicability and
utility of the Marseille classication in routine clinical practice.
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Cambridge Classication
The Cambridge working group met in 1983 and developed the Cambridge classication system for pancreatitis [7]. This system has since formed the basis for many
revised or modied systems [1]. The authors focused on ve aspects of disease in
their development of this classication system: etiology, pancreatic exocrine function, imaging ndings, histology, and surgery [7]. They concluded that acute and
chronic pancreatitis are dened by the reversibility of pancreatic changes—acute
pancreatitis may result in a temporary alteration in function, whereas chronic pancreatitis is dened by irreversible changes. Although etiology, exocrine function,
and histology were deemed to be important in dening chronic pancreatitis, specic
guidelines were not included for their use in this classication.
The Cambridge group specically graded chronic pancreatitis based on imaging
ndings using endoscopic retrograde cholangiopancreatography (ERCP), ultrasound (US), or computed tomography (CT). They divided the ndings into ve
groups: (1) normal; (2) equivocal; (3) mild; (4) moderate; and (5) marked. For
ERCP, the grading system focused primarily on the location and number of abnormal duct branches, with marked chronic pancreatitis also including other changes
such as pancreatic duct stones, obstruction, and gland enlargement. Similar to the
Marseille classication, the authors acknowledge that the clinical course does not
always mirror morphological changes, especially early in a patient’s clinical course.
Rosemont Classication
The Rosemont classication is an imaging-based classication system published in
2009 [8]. It was developed by a consensus group of 32 endoscopic ultrasound (EUS)
practitioners from North America and Japan. The group anonymously voted on
statements focused on denitions and the predictive value of features seen on EUS
and whether each feature should be considered a major or minor feature. Major
features were further subdivided into A and B categories based on their predictive
value. The threshold for consensus was deemed to be two-thirds of the
participants.
The features were classed as parenchymal or ductal. The parenchymal features in
this classication system include at least three areas of hyperechogenicity >2mm
with shadowing (major A), three or more >5-mm lobules in the body or tail of the
pancreas (major B if contiguous, minor if not), three or more hyperechoic areas
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E. Hensler and S. Ayloo
>3mm without shadowing (minor), >2-mm cysts (minor), and three or more hyperechoic lines at least 3-mm long running in two or more directions in the same plane
(also called strands; minor). The ductal features include calculi in any part of the
main pancreatic duct (deemed to be the most predictive feature; major A), irregularity of the main duct in the body or tail (minor), at least three dilated side branches
>1mm that connect to the main duct in the body or tail (minor), dilation (>3.5mm
in the body, >1.5mm in the tail) of the main pancreatic duct (minor), and hyperechogenicity of the main duct wall across at least 50% of the portion of the duct in
the body and tail (minor). These features were then combined to create a diagnostic
classication system with four categories: consistent with, suggestive of, or indeterminate for chronic pancreatitis, and normal (Table6.2).
TIGAR-O Classication
Unlike earlier published classication systems, the TIGAR-O system focuses on the
etiology of chronic pancreatitis [9]. The authors of this system assert that other classication methods focus on the end result of the pancreatic damage seen in patients
with chronic pancreatitis, whereas a focus on etiology allows for more precision to
predict disease progression and to manage these patients. The potential etiologies
are divided into the following categories: toxic-metabolic, idiopathic, genetic, autoimmune, recurrent severe acute pancreatitis, and obstructive. Patients with multiple
risk factors are categorized based on the risk factor associated with the highest risk
of developing chronic pancreatitis. The toxic-metabolic category includes
Table 6.2 Summary of imaging ndings in chronic pancreatitis in accordance with the Cambridge
classication [7]
Grade ERCP ndings US/CT ndings
1. Normal No abnormalities No abnormalities
2. Equivocal <3 abnormal branch ducts Dilated main pancreatic duct, enlarged gland,
3. Mild >3 abnormal branch ducts At least two of the above criteria
4. Moderate Main pancreatic duct and
branch duct abnormalities
5. Marked Main pancreatic duct and
branch duct abnormalities
AND
>1cm cavity, enlarged
gland-lling defects/stones,
obstruction or stricture, or
neighboring organ involvement
ERCP endoscopic retrograde cholangiopancreatography, US ultrasound, CT computed tomography
cavities, ductal irregularities, acute
pancreatitis, hyperechoic duct, irregular head/
body of gland, or heterogeneous pancreatic
parenchyma
At least two of the above criteria
At least two of the above criteria
6 SAGES Manual: Chronic Pancreatitis–Classication andMedical Management
103
pancreatitis due to alcohol consumption, smoking, hypercalcemia, hyperlipidemia,
medications, toxins, and chronic kidney disease. The idiopathic category includes
minimal change pancreatitis and tropical pancreatitis. The genetic category includes
mutations in PRSS1 (autosomal dominant), CFTR (autosomal recessive), and
SPINK1 (autosomal recessive). The autoimmune category includes conditions that
can be associated with chronic pancreatitis, such as inammatory bowel disease,
primary biliary cirrhosis, primary sclerosing cholangitis, and Sjögren syndrome.
Recurrent severe acute pancreatitis occurs when patients experience an incomplete
recovery from attacks of acute pancreatitis. These recurrent attacks can be due to a
number of causes, including alcohol and hyperlipidemia. The obstructive category
includes obstructive features associated with chronic pancreatitis, such as tumors,
sphincter of Oddi dysfunction, brosis causing duct obstruction, trauma, or anatomical abnormalities such as pancreatic divisum.
Although different etiologies may indeed necessitate different management
strategies or present unique treatment options, this classication system addresses
only one aspect of the disease and does not consider symptom severity or pancreatic
dysfunction.
M-ANNHEIM Classication
The M-ANNHEIM classication, published in 2007, sought to create a unied classication system that combined risk factors, severity, and clinical course [10].
Specically, this system classies pancreatitis by risk factors, clinical staging, diagnostic criteria, imaging criteria, and severity scoring. Although comprehensive, this
system is limited by the large amount of data needed to accurately classify patients
and its overall complexity [1].
The risk factors are grouped as follows: alcohol use, nicotine use, nutritional,
hereditary, efferent duct factors, immunologic, and miscellaneous/metabolic [10].
Alcohol use is stratied by intake per day, with moderate intake dened as <20g
ethanol, increased intake as 20–80g ethanol, and excessive intake as >80g ethanol.
Smoking history is quantied in pack-years. Nutritional factors include a history of
hyperlipidemia or a diet high in fat or protein. Genetic factors include mutations in
PRSS1, SPINK1, and CFTR, as well as patients with an apparent autosomal dominant inheritance pattern without an identied gene mutation. This hereditary category also includes idiopathic and tropical pancreatitis. Efferent duct factors include
features that lead to obstruction, such as tumors, scarring, sphincter of Oddi dysfunction, pancreas divisum, and congenital abnormalities. The immunologic category includes autoimmune diseases that can lead to chronic pancreatitis, including
inammatory bowel disease, Sjögren syndrome, primary sclerosing cholangitis, and
primary biliary cirrhosis. Miscellaneous/metabolic factors include hypercalcemia,
chronic kidney disease, toxins, and medications.
The authors describe a clinical-stage classication that ranges from stage 0 to IV,
with each stage being further subdivided. Stage 0 is subclinical and includes patients
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E. Hensler and S. Ayloo
without chronic symptoms. This can include patients who never develop symptoms
(stage 0a), those who have a single acute episode (stage 0b), and those who have an
acute episode with complications (stage 0c). Stage I includes patients without evidence of exocrine or endocrine insufciency and is subdivided into patients with
recurrent acute episodes (stage Ia), those with pain between acute attacks (stage Ib),
and those who meet stage Ia or Ib and also have complications (stage Ic). Stage II
patients have evidence of partial exocrine or endocrine insufciency (but not both).
Stage IIa patients do not have associated pain, stage IIb patients do have associated
pain, and stage IIc patients meet stage IIa or IIb criteria with complications. Stage
III patients have both endocrine and exocrine insufciency, with stage IIIa including
patients with pain and stage IIIb including patients with complications. Stage IV
represents pancreatic burnout. These patients do not have pain but have both endocrine and exocrine dysfunction with or without complications.
For diagnostic criteria, the authors classied patients as having denite, probable, or borderline chronic pancreatitis based on imaging, functional, and histological characteristics. Denite chronic pancreatitis is dened as a typical symptom
history plus at least one of the following: calcications, Cambridge 4 or 5 duct
abnormalities, steatorrhea that improves with pancreatic enzyme replacement, or
histologic changes consistent with chronic pancreatitis. Patients with probable
chronic pancreatitis have one or more of the following features: Cambridge 3 duct
abnormalities, recurrent pancreatic pseudocysts, abnormal exocrine function, or
abnormal endocrine function. Patients with borderline chronic pancreatitis have a
typical symptom history without any of the previously described criteria. Pancreatitis
due to alcohol use is also included as a separate subcategory based on the daily
intake amount.
The imaging criteria were determined using CT, magnetic resonance imaging,
magnetic resonance cholangiopancreatography, or EUS. CT, magnetic resonance
imaging (MRI), and magnetic resonance cholangiopancreatography (MRCP) criteria were based on the Cambridge classication, while EUS criteria included the size
of the pancreas, the presence of cysts, hypoechoic or hyperechoic areas, lobulations,
hyperechogenicity of the wall of the main duct, main duct dilation or irregularity,
dilated side branch ducts, or calcications. The authors classied CT, MRI, or
MRCP imaging as normal (no abnormalities), equivocal (one abnormality), mild (at
least two abnormalities with a normal main duct), moderate (at least two abnormalities, including minor changes to the main duct), or marked (two or more abnormalities, with one of the “marked” criteria from the Cambridge classication). They
proposed that EUS examinations with one to four abnormal ndings should be classied as equivocal/mild, whereas those with at least ve abnormal ndings should
be classied as moderate/marked.
The severity index assigns a numeric score in each of the following categories:
subjective pain, use of pain medications, need for surgery, exocrine insufciency,
endocrine insufciency, staging based on imaging, and presence of complications.
Each category is scaled from 0 to 4, with complications and surgical interventions
able to be counted multiple times if they occurred multiple times in the patient’s
clinical course. This generates a total score, with 0–5 points correlating to minor
6 SAGES Manual: Chronic Pancreatitis–Classication andMedical Management
severity or M-ANNHEIM A, 6–10 points as increased severity or M-ANNHIEM B,
11–15 points as advanced severity or M-ANNHEIM C, 16–20 points as marked
severity or M-ANNHEIM D, and >20 points as exacerbated severity or
M-ANNHEIM E.
All these criteria taken together make up the M-ANNHEIM classication system. The authors stated that their goal was to create a comprehensive, simple-to-use
system to classify patients with chronic pancreatitis to more easily compare patients’
clinical courses and treatments. They also theorized that this system could be used
to identify trends in disease progression from different etiologies. However, given
the number of parameters included, this system is somewhat cumbersome for routine use.
105
ABC Classication
The ABC classication system was developed as a simple, noninvasive way to stratify patients with pancreatitis by disease severity, with the goal to group patients by
clinical stage to determine treatment needs [11]. Patients are placed in group A if
they have no pain, group B if they have pain but no complications, and group C if
they have pain and complications. Complications include pseudocysts, obstruction
of the biliary system or duodenum, portal hypertension, pancreatic ascites, and cancer. Each of the groups is further subdivided based on functional impairment (no
impairment, endocrine only, exocrine only, or both endocrine and exocrine). Of
note, this system does not include any imaging characteristics and, instead, focuses
on the symptoms of pain and pancreatic insufciency. The authors state that this is
because imaging ndings can be nonspecic and do not necessarily correlate with
disease severity. This focus on symptomatology rather than imaging may make this
a more clinically relevant classication system though it is also limited by its narrow focus.
Manchester Classication
The Manchester classication was developed as a clinical system and divides
patients with pancreatitis into three stages based on symptoms and disease complications [12]. The authors retrospectively identied 41 patients with radiographic
evidence of chronic pancreatitis (by MRCP, CT, or ERCP) and classied them into
mild, moderate, or end-stage disease. Patients were categorized as mild if they had
pain but did not require frequent pain medication. These patients also had preserved
pancreatic functions (both endocrine and exocrine) and did not have any complications. Patients with moderate disease had pain that required at least weekly pain
medication, and some level of pancreatic dysfunction, but no complications. Patients
with end-stage disease had diabetes or steatorrhea, as well as evidence of a
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E. Hensler and S. Ayloo
complication related to chronic pancreatitis, such as portal hypertension, duodenal
stenosis, or stricture in the biliary tree.
Based on this classication method, 44% of the patients studied had mild disease, 46% had moderate disease, and 10% had end-stage disease. The authors then
reviewed 10years of clinical records for these patients and reclassied them to
determine the amount of disease progression during this time period. After 10years,
no patients were considered to have mild disease. The rates of diabetes and steatorrhea also increased dramatically over the study period. At the initial time point, 5%
of patients had steatorrhea, and this number rose to 27% at the 10-year time point.
Initially, 5% of patients had diabetes, and this number rose to 61% by the end of the
10-year study period.
One of the strengths of this system is that it captures the progression of clinical
disease that patients experience. It also considers that pain may not be present in
end-stage disease without excluding patients who continue to experience pain. It is
somewhat limited by its design, having been developed retrospectively and based on
referrals to a tertiary care center. Its applicability may also be limited, as the majority of patients (78%) had disease resulting from alcohol use.
Heidelberg Classication
The Heidelberg classication sought to provide a simple method of categorizing
patients with pancreatitis that would offer insight into treatment and prognosis,
similar to the Child–Pugh classication in liver disease [13]. The Heidelberg system
combines clinical and radiographic criteria for diagnosis and straties patients by
disease severity (Table6.3). Stage A is considered early chronic pancreatitis. These
patients may have pain or recurrent acute episodes, but they do not exhibit disease
complications. Patients in stage A also have overall preservation of their pancreatic
function although they have mild dysfunction without overt symptoms. For example, these patients may have abnormal glucose tolerance without diabetes or mildly
impaired exocrine function without steatorrhea.
Stage B is the intermediate stage. Patients in this group again have overall preservation of pancreatic function (no diabetes or steatorrhea) but have experienced
complications of chronic pancreatitis. These complications include biliary or duodenal obstruction, vascular occlusion, clinically signicant pseudocysts, pancreatic
stula or ascites, or a complication that impacts a neighboring organ (such as the
spleen or colon). Stage C is considered an end-stage disease and is further subdivided into three categories: C1, patients with endocrine dysfunction (i.e., diabetes);
C2, patients with exocrine dysfunction (i.e., steatorrhea); and C3, patients with both
endocrine and exocrine dysfunction with or without complications.
The authors applied their classication system to 191 patients and then restaged
the patients every 6months for 3years. They found that, at each time point, approximately 4% of patients had developed new disease complications, which suggested a
steady rate of disease progression. However, all patients had received operative
6 SAGES Manual: Chronic Pancreatitis–Classication andMedical Management
Table 6.3 Summary of the Rosemont classication [8]
Features
Consistent with chronic pancreatitis – 1 Major A and ≥3 minor
– 1 Major A and Major B
– 2 Major A
Suggestive of chronic pancreatitis – 1 Major A and <3 minor
– Major B and ≥3 minor
– At least 5 minor
Indeterminate for chronic pancreatitis – 0 Major and 3–4 minor
– Major B
– Major B and <3 minor
Normal – 0 Major and 0–2 minor
Major A criteria: at least three areas of hyperechogenicity >2mm with shadowing; calculi in any
part of the main pancreatic duct
Major B criteria: three or more contiguous >5-mm lobules in the body or tail of the pancreas
Minor criteria: three or more noncontiguous >5-mm lobules in the body or tail of the pancreas;
three or more hyperechoic areas >3mm without shadowing; >2-mm cysts; three or more hyperechoic lines at least 3-mm long running in two or more directions in the same plane; irregularity of
the main duct in the body or tail; at least three dilated side branches >1mm that connect to the main
duct in the body or tail; dilation (>3.5mm in the body, >1.5mm in the tail) of the main pancreatic
duct; hyperechogenicity of the main duct wall across at least 50% of the portion of the duct in the
body and tail
Table 6.4 Summary of the Heidelberg classication [13]
Stage Description
A – Early chronic pancreatitis
– Pain, recurrent acute pancreatitis episodes without complications
– Preserved pancreatic function
B – Intermediate
– Preserved pancreatic function
– Complications present (e.g., biliary or duodenal obstruction, vascular occlusion,
clinically signicant pseudocysts, pancreatic stula or ascites, or a complication
impacting a neighboring organ)
C – End-stage
– C1: endocrine dysfunction
– C2: exocrine dysfunction
– C3: both endocrine and exocrine dysfunction ± complications
107
intervention for their disease, so this trend of progression may not be indicative of
the general population of patients with chronic pancreatitis (Table6.4).
Chronic Pancreatitis Prognosis Score Classication
The COPPS was developed to evaluate the risk of hospital admission for patients
with chronic pancreatitis and was modeled after the Child–Pugh score in liver disease [14]. This system uses multiple subjective and objective variables to generate a
108
score that is correlated to a disease stage. The authors examined clinical, laboratory,
and imaging variables and identied correlations with hospital readmissions over a
12-month period. These initial variables included levels of hemoglobin A1c, total
and conjugated bilirubin, stool elastase, alanine aminotransferase (ALT), gammaglutamyl transferase (GGT), international normalized ratio (INR), albumin,
C-reactive protein (CRP), platelets, urea, mean corpuscular volume (MCV), and
triglycerides, and the Cambridge score, pain rating, and body mass index (BMI).
Of these, only BMI and levels of hemoglobin A1c, CRP, and platelets correlated
to hospital readmission. The authors included the pain rating in the scoring system
because of its impact on patient quality of life, despite the lack of correlation to
hospital readmission. Patients could receive 1–3 points for each variable, which
depended on the reference ranges set by the authors based on an initial cohort of 91
patients, for a maximum of 15 points on this scale. Patients were considered to be
COPPS A if they had 5–6 points, COPPS B with 7–9 points, and COPPS C with
10–15 points. In this initial cohort, the COPPS stage correlated with hospital readmissions (both in general and for pancreas-specic reasons), number of days spent
in the hospital, and number of endoscopic treatments performed.
The authors then validated this scoring system in a second cohort of 129 patients,
with similar results. This system is distinct from the other classication systems
previously discussed in that it was developed using prospective recruitment of
patients. However, the COPPS is limited in scope, as it only includes hospitalized
patients and so may not be widely applicable.
E. Hensler and S. Ayloo
Medical Management ofChronic Pancreatitis
Chronic pancreatitis is a complicated disease that can be very difcult to treat, given
the number of etiologies, presenting symptoms, and lack of correlation between
imaging and clinical course. The lack of a widely accepted classication system
also contributes to the complexity of patient management. Overall, medical management is the rst step to treat chronic pancreatitis and primarily focuses on reduction of the frequency of acute episodes, reduction of patient symptoms, and
management of the effects of pancreatic dysfunction. A summary of treatment
modalities is given in Fig.6.1.
Reducing Frequency ofAcute Pancreatitis
Acute episodes of pancreatitis can lead to chronic pancreatitis or worsen symptoms
in those with chronic pancreatitis. Therefore, reduction in the frequency of these
attacks is an important component of the medical management of pancreatitis [15].
Risk factor modication is the main method to reduce the frequency of acute attacks.
Alcohol use is the primary modiable risk factor for chronic pancreatitis, as it is one