ABDOMINAL RADIOLOGY

Autoimmune pancreatitis: multidetector-row computedtomography (MDCT) and magnetic resonance (MR) findingsin the Italian experience

Rossella Graziani • Simona Mautone • Maria Chiara Ambrosetti •

Riccardo Manfredi • Thomas J. Re • Lucia Calculli •

Luca Frulloni • Roberto Pozzi Mucelli

Received: 9 August 2012 / Accepted: 30 July 2013

� Italian Society of Medical Radiology 2014

Abstract Multidetector-row computed tomography

(MDCT) and magnetic resonance (MR) imaging are cur-

rently the most frequently performed imaging modalities

for the study of pancreatic disease. In cases of suspected

autoimmune pancreatitis (AIP), a dynamic quadriphasic

(precontrast, contrast-enhanced pancreatic, venous and late

phases) study is recommended in both techniques. In the

diffuse form of autoimmune pancreatitis (DAIP), the pan-

creatic parenchyma shows diffuse enlargement and

appears, during the MDCT and MR contrast-enhanced

pancreatic phase, diffusely hypodense and hypointense,

respectively, compared to the spleen because of lympho-

plasmacytic infiltration and pancreatic fibrosis. During the

venous phase of MDCT and MR imaging, the parenchyma

appears hyperdense and hyperintense, respectively, in

comparison to the pancreatic phase. In the delayed phase of

both imaging modalities, it shows retention of contrast

media. A ‘‘capsule-like rim’’ may be recognised as a

peripancreatic MDCT hyperdense and MR hypointense

halo in the T2-weighted images, compared to the paren-

chyma. DAIP must be differentiated from non-necrotizing

acute pancreatitis (NNAP) and lymphoma since both dis-

eases show diffuse enlargement of the pancreatic

parenchyma. The differential diagnosis is clinically diffi-

cult, and dynamic contrast-enhanced MDCT has an

important role. In the focal form of autoimmune pancrea-

titis (FAIP), the parenchyma shows segmental enlargement

involving the head, the body-tail or the tail, with the same

contrast pattern as the diffuse form on both modalities.

FAIP needs to be differentiated from pancreatic adeno-

carcinoma to avoid unnecessary surgical procedures, since

both diseases have similar clinical and imaging presenta-

tion. The differential diagnosis is clinically difficult, and

dynamic contrast-enhanced MDCT and MR imaging both

have an important role. MR cholangiopancreatography

helps in the differential diagnosis. Furthermore, MDCT and

MR imaging can identify the extrapancreatic manifesta-

tions of AIP, most commonly biliary, renal and retroperi-

toneal. Finally, in all cases of uncertain diagnosis, MDCT

and/or MR follow-up after short-term treatment

(2–3 weeks) with high-dose steroids can identify a signif-

icant reduction in size of the pancreatic parenchyma and, in

FAIP, normalisation of the calibre of the upstream main

pancreatic duct.

Keywords Chronic pancreatitis � Autoimmune

pancreatitis � Acute pancreatitis � Computed tomography �Magnetic resonance � Steroid treatment

Autoimmune pancreatitis (AIP): definition

and classification

Autoimmune pancreatitis (AIP) is a form of chronic pan-

creatitis associated with autoimmune processes. Distinct

histological and clinical profiles reveal two subtypes of

AIP, indistinguishable on the basis of imaging alone: type

1, or lymphoplasmacytic sclerosing pancreatitis (LPSP),

R. Graziani (&) � S. Mautone � M. C. Ambrosetti �R. Manfredi � T. J. Re � R. P. Mucelli

Department of Radiology, ‘‘G.B. Rossi’’ Hospital, University

of Verona, P.le L.A. Scuro 11, 37134 Verona, Italy

e-mail: rossella.paola.graziani@gmail.com

L. Calculli

Department of Radiology, Sant’Orsola-Malpighi Hospital,

University of Bologna, 9 Via Massarenti, Bologna, Italy

L. Frulloni

Department of Medicine, ‘‘G.B. Rossi’’ Hospital,

University of Verona, P.le L.A. Scuro 10, Verona, Italy

123

Radiol med

DOI 10.1007/s11547-013-0373-9

and type 2, or idiopathic duct-centric pancreatitis (IDCP)

[1]. Type 1, LPSP, or AIP without granulocyte epithelial

lesions, seems to be an IgG4-related multiorgan disease,

characterised by elevated serum IgG4 levels, multiple ex-

trapancreatic organ involvement and IgG4-rich lympho-

plasmacytic infiltrate on histology in all the affected organs

[2, 3]. This form characteristically responds to steroid

treatment, though relapse in the pancreas or other affected

organs is common. In type 2 AIP, IDCP or AIP with

granulocyte epithelial lesions, there is no extrapancreatic

organ involvement or IgG4-rich infiltrate on histology, and

serum IgG4 elevation is unlikely. This form appears to be a

pancreas-specific disorder and is histologically character-

ised by the presence of neutrophils with typical granulocyte

epithelial lesions.

The diagnosis of AIP is challenging even at expert

centres and many different diagnostic criteria have been

developed. Recently, the International Consensus Diag-

nostic Criteria (ICDC) have unified these diagnostic crite-

ria accommodating regional differences in practice. The

comprehensive criteria that must be fulfilled for the diag-

nosis include pancreatic imaging of the parenchyma and

ductal system, serological and histopathological findings,

other organ involvement and response to steroid treatment

[1].

The clinical presentation overlaps with other forms of

acute and chronic pancreatitis, but without a history of

alcohol or tobacco abuse or biliary stone disease. AIP may

vary in its clinical presentation depending on the pancreatic

distribution of disease (focal or diffuse) and on the specific

site involved (head, body or tail of the pancreas) [4–21]. In

the case of focal distribution in the pancreatic head,

patients frequently present painless jaundice. In diffuse

forms or in focal distribution in the pancreatic body-tail,

patients may present pancreatic abdominal pain in the

epigastric region, irradiating to the back with or without

jaundice [8–21]. Therefore, the clinical presentation of AIP

may mimic pancreatic adenocarcinoma in the focal forms

and pancreatic lymphoma or non-necrotizing acute pan-

creatitis (NNAP) in the diffuse forms [22–26].

In evaluating patients with suspected pancreatic disease,

acute or chronic pancreatitis or pancreatic neoplasms,

multidetector-row computed tomography (MDCT) and

magnetic resonance (MR) are the imaging modalities of

choice [15–17, 27–33]. In the specific case of suspected

AIP, a dynamic quadriphasic study (precontrast, contrast-

enhanced arterial, pancreatic, venous and late phases) is

recommended for both techniques.

Technically, in MDCT of the pancreas, contrast medium

administration typically involves the use of bolus tracking

software with a region of interest (ROI) placed over the aorta

and a predetermined attenuation threshold of 100 HU.

Pancreatic arterial and portal venous phase images are

acquired 20–30 and 60–70 s after bolus tracking, respec-

tively, and the delayed phase images 180 s after the begin-

ning of the injection. A collimation value between a

maximum of 2.5 mm and a minimum of 0.625 mm is rec-

ommended. The standard reconstruction thickness used

during the pancreatic and portal venous phase is 1 mm, with

an interval of 0.5 mm, whereas during the late phase it is

2–1 mm, with a range of 1–0.5 mm. Postprocessed coronal

and curved MDCT multiplanar reconstruction (MPR) ima-

ges are recommended in cases of suspected AIP.

Pancreatic MR and MR cholangiopancreatography

(MRCP) imaging must be performed on a 1.5 T scanner

using a surface phased-array body coil. Patients are asked to

fast for 4–6 h before the MR examination. To eliminate

overlapping fluid-containing organs on T2-weighted MRCP

images, 50–150 ml of superparamagnetic iron oxide parti-

cles is administered 10–20 min before the MR examination.

Pancreatic MR imaging includes the following sequences:

axial T1-weighted gradient echo, axial T1-weighted fat-

saturated, axial T2-weighted fat-saturated rapid acquisition

with relaxation enhancement (RARE), T2-weighted half-

Fourier RARE, coronal true fast imaging in the steady-state

precession (true-FISP), axial and coronal, coronal oblique

2D half-Fourier RARE cholangiopancreatography, axial

fat-saturated 3D volumetric gradient echo. The dynamic

study, during gadolinium-chelate injection, is obtained by

means of a 3D volumetric gradient-echo pulse sequence

using parallel imaging. A quadriphasic dynamic study is

performed during injection of 0.1 mmol/kg body weight of

gadolinium chelates by means of a power injector at

2–2.5 ml/s, by acquiring the precontrast-phase, late arterial/

pancreatic phase (35–45 s), portal venous phase (75–80 s),

and delayed phase ([180 s). For diffusion-weighted imag-

ing (DWI), a spin-echo echoplanar sequence is performed

with a b value of 0, 50, 600 s/mm2. An apparent diffusion

coefficient (ADC) map is automatically calculated for each

section by the system’s software.

AIP: MDCT findings

Diffuse forms (DAIP)

The pancreatic parenchyma shows [15, 34–36] diffuse

enlargement (Fig. 1) and appears isodense compared to the

spleen on precontrast MDCT images (Fig. 1a); pancreatic

ductal stones are almost always absent at onset but they

may be present in advanced stages [37, 38].

Dynamic contrast-enhanced MDCT study is helpful in

the diagnosis: during the pancreatic phase, the parenchyma

is diffusely hypodense compared to the spleen because of

the lymphoplasmacytic infiltration and pancreatic fibrosis

(Fig. 1b, e). During the venous phase, the parenchyma

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Fig. 1 Diffuse autoimmune pancreatitis (DAIP) before and after

short-term high-dose steroid treatment. Multidetector computed

tomography (MDCT) imaging. Precontrast (a), contrast-enhanced

pancreatic (b, e), venous (c, f) and late (d) phases. Axial (a–d) and

multiplanar curved reconstructions (e, f) MDCT images. Diffuse

pancreatic enlargement is present (a–e). The pancreatic parenchyma

is homogeneously isodense compared to the spleen on the precontrast

MDCT image (a); pancreatic stones are absent. The pancreatic

parenchyma appears hypodense compared to the spleen during

contrast-enhanced MDCT pancreatic phase (b, e). During the portal

venous phase, it becomes more dense, appearing hyperdense

compared to the previous pancreatic phase (c). During the late phase

(d), the pancreatic parenchyma shows retention of contrast medium: it

is hyperdense compared to the previous venous phase. In the delayed

phase (d), a peripancreatic hyperdense halo is visible (‘‘capsule-like

rim’’: arrow). The intrapancreatic segment of the common bile duct is

slightly dilated (arrow head); the intrahepatic bile ducts are normal.

In the left kidney, a solid cortical lesion is present which later proved

to be chronic autoimmune pyelonephritis on biopsy (black arrows);

the right kidney shows a cystic lesion. Retroperitoneal fluid film,

peripancreatic stranding and enlarged lymphonodes are absent. Three

weeks after high-dose steroid treatment (f), the pancreatic paren-

chyma shows normal thickness and parenchymal vascularisation has

become normal during the contrast-enhanced pancreatic phase

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appears hyperdense in comparison to the previous pan-

creatic phase (Fig. 1c) and it shows retention of contrast

media during the delayed phase, becoming more hyper-

dense compared to the previous venous phase (Fig. 1d)

[37–43].

The pancreatic margins are smooth and well defined in

all phases of the dynamic contrast-enhanced MDCT study

(Fig. 1), probably due to peripancreatic tissue inflammation

[12, 13]. A capsule-like rim, appearing as a peripancreatic

hyperdense halo compared to the parenchyma, may be

present in the delayed phase (Fig. 1d). According to some

authors, this peripheral rim of delayed contrast enhance-

ment is due to the presence of a chronic inflammatory

process and fibrous tissue involving the peripancreatic fat

[15, 20, 21, 44]. The periductal inflammatory cell infiltra-

tion and fibrous tissue centred around the pancreatic ducts

[12, 13, 44–49] produce diffuse narrowing of the main

pancreatic duct (MPD). The MPD is frequently not visible

within a DAIP lesion in axial and MPR MDCT images

(Fig. 1a–e). If local MPD stenosis is present, the upstream

duct is dilated. Patients with AIP often demonstrate

enhancement of the MPD wall on CT imaging (the

‘‘enhanced duct sign’’) [42, 43] and this could reflect

periductal inflammatory changes. The enhanced duct sign

is strongly associated with the abnormal enhancement area

of the pancreas in AIP and, although relatively uncommon,

this finding may be useful for the diagnosis of AIP.

Both the enhanced duct sign and the inability to visu-

alise the MPD lumen within a DAIP lesion can aid in the

diagnosis of AIP. Furthermore, the side branches are not

visible in axial and MPR images. The intrapancreatic

segment of the common bile duct (CBD) may be normal or

stenotic in DAIP. Retroperitoneal fluid film, recorded at

MDCT images as thickening of the anterior pararenal

fascial plane, is never present in DAIP. Also peripancreatic

stranding, represented by inflammatory changes of peri-

pancreatic fat in mild acute non-necrotizing pancreatitis,

recorded as a hypodense peripancreatic halo in all phases

of CT examination [32, 37] is absent in DAIP [50].

DAIP must be differentiated from NNAP and lymphoma

since both these pathological conditions show diffuse

enlargement of the pancreatic parenchyma [19, 25, 51, 52].

In both DAIP and NNAP, pancreatic abdominal pain

with epigastric location irradiating to the back, increase of

serum amylase and lipase and diffuse pancreatic enlarge-

ment are frequently present [28–31]. The clinical differ-

entiation of DAIP from NNAP at onset is useful since only

DAIP responds to steroid treatment because of its auto-

immune pathogenesis [32–38, 45] (Fig. 2). Dynamic con-

trast-enhanced MDCT is helpful in differentiating DAIP

from NNAP because the parenchymal vascularisation is

significantly different in the two diseases [50, 53]. During

the pancreatic phase, the glandular parenchyma is

hypodense in DAIP (Fig. 1b, e) due to lymphoplasmacytic

infiltrates and pancreatic fibrosis, and isodense compared to

the spleen in NNAP, due to interstitial oedema without

areas of necrosis (Fig. 2b, d). During the portal venous

phase, DAIP appears hyperdense compared to the previous

pancreatic phase (Fig. 1c), while in NNAP the parenchyma

most frequently becomes hypodense during the portal

venous phase (Fig. 2c). DAIP shows retention of the con-

trast medium in the delayed phase (Fig. 1d) while NNAP

shows parenchymal wash-out. Recently, this vascularisa-

tion pattern of DAIP has been assessed using the rate of

relative variation in enhancement from the previous phase

or Relative Enhancement Rate across all phases of the

MDCT study [50]. Evaluation of the Relative Enhancement

Rate confirmed the particular vascularisation pattern of

DAIP, different from that of NNAP. The presence of a

peripheral rim of contrast enhancement in the delayed

MDCT phase, due to chronic inflammatory processes and

fibrosis involving the fatty peripancreatic tissue, is highly

suggestive of AIP (Fig. 1d) and absent in NNAP. A ret-

roperitoneal fluid film, a typical finding in NNAP (Fig. 2a–

d) due to retroperitoneal inflammation with peripancreatic

oedema, is absent in DAIP. Peripancreatic stranding,

appearing as a hypodense peripancreatic halo in all phases

of the MDCT examination, is due to mild inflammatory

changes of the fat surrounding the pancreas and is fre-

quently present in NNAP (Fig. 2a–d), whereas it is absent

in DAIP. A statistically significant difference in the two

groups of patients (DAIP and NNAP) regarding the pre-

sentation of peripancreatic stranding and retroperitoneal

fluid has been demonstrated [50]. In conclusion, the pattern

of MDCT contrast enhancement of DAIP and NNAP,

particularly considering the Relative Enhancement Rate

parameters [50], provides qualitative and quantitative clues

for differentiating the diseases. The retroperitoneal findings

of peripancreatic stranding and retroperitoneal fluid film,

characteristic of NNAP, and the late-phase peripheral rim

enhancement, characteristic of DAIP, can also assist in the

differential diagnoses.

Both in DAIP and in pancreatic lymphoma (Fig. 2e, f),

glandular enlargement and reduced parenchymal enhance-

ment in the pancreatic phase are present. In DAIP, the pan-

creatic parenchyma becomes more dense in the venous and

delayed phases, while in lymphoma it remains hypodense in

all MDCT phases. A late enhancing capsule-like rim is

suggestive of DAIP, whereas the presence of peripancreatic

and periaortic lymphadenopathy and/or focal solid splenic

lesions suggests the presence of lymphoma [54–56].

Focal forms (FAIP)

Focal parenchymal enlargement may be present exclu-

sively in the pancreatic head (Fig. 3a–d), in the body and

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Fig. 2 Diffuse autoimmune pancreatitis (DAIP): differential diagno-

sis with non-necrotizing acute pancreatitis (NNAP) and pancreatic

lymphoma. MDCT imaging. Precontrast (a), contrast-enhanced

pancreatic (b, d), venous (c, e, f) phases. Axial (a–c, e, f) and

multiplanar curved reconstructions (d) MDCT images. NNAP (a–d).

Diffuse pancreatic enlargement is present. Pancreatic parenchyma is

homogeneously isodense compared to the spleen on the precontrast

MDCT image (a); pancreatic stones are absent. The pancreatic

parenchyma appears isodense compared to the spleen during the

contrast-enhanced pancreatic phase (b, d). Areas of pancreatic

necrosis are not recognisable because of the mild inflammatory

pancreatic process and oedema. During the portal venous phase, the

pancreatic parenchyma becomes hypodense compared to the previous

pancreatic phase (c). A retroperitoneal fluid film is present in the

pararenal anterior space (arrow). The pancreatic gland is surrounded

by a hypodense halo in all MDCT phases (peripancreatic stranding:

arrow head) due to mild inflammatory changes of peripancreatic fat.

Pancreatic lymphoma (e, f). The pancreatic parenchyma appears

enlarged (especially in the pancreatic head) and hypodense during the

portal venous phase compared to the spleen. Diffuse intra- and extra-

hepatic bile duct dilatation (black arrow) is present. Pancreatic core

biopsies confirmed the diagnosis of non-Hodgkin lymphoma

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tail (Fig. 3e, f), or only in the pancreatic tail. Enlarged

glandular portions of the pancreas appear isodense com-

pared to the spleen on precontrast MDCT images (Fig. 3a).

Pancreatic ductal stones are always absent.

During the contrast-enhanced pancreatic phase of

MDCT, the enlarged parenchyma appears hypodense

(Fig. 3b, e) compared to the spleen and the unaffected

adjacent parenchyma, due to inflammatory cell infiltration

and glandular fibrosis [50]. During the venous phase

(Fig. 3c), the parenchyma in FAIP becomes more dense,

and appears hyperdense compared to its attenuation during

the previous pancreatic phase. During the delayed phase,

FAIP shows retention of contrast medium: the parenchyma

becomes more hyperdense compared to its attenuation in

the previous venous phase and to the adjacent unaffected

glandular portions.

As in DAIP, the pancreatic margins are smooth and well

defined in all phases of dynamic contrast-enhanced MDCT

(Fig. 3), probably due to the peripancreatic tissue inflam-

matory process. A capsule-like-rim appearing as a hyper-

dense halo compared to the parenchyma surrounding the

areas involved by FAIP may be present in the delayed

phase. This is probably due to chronic inflammatory and

fibrotic processes of the peripancreatic fat. When this

peripheral rim is present, it is highly suggestive of AIP [15,

40, 57].

The MPD is not visible within FAIP or it may present a

focal short stenosis with a short segment of upstream

dilatation in the axial and MPR MDCT images, reflecting

inflammatory cell infiltrates and fibrosis centred around the

pancreatic ducts (Fig. 3). The upstream MPD may be

dilated (Fig. 3), as it is in patients with adenocarcinoma, or

may be normal. Patients with FAIP also often demonstrate

enhancement of the MPD walls on MDCT imaging [42,

43]. This ductal enhancement may reflect periductal

inflammatory changes and, although relatively uncommon,

this finding may be useful for the diagnosis of AIP (Fig. 3e,

f). The enhanced duct sign is strongly associated with the

abnormal enhancement area of the pancreas in AIP. The

side branches are also not visible in the axial and MPR

MDCT images. The intrapancreatic segment of the CBD

may be normal or stenotic (Fig. 3) in FAIP of the pan-

creatic head. If CBD stenosis is present, suprapancreatic

CBD has an enlarged calibre.

FAIP needs to be differentiated from pancreatic ade-

nocarcinoma (Fig. 4) since both these diseases show focal

enlargement, frequently in the pancreatic head, bile duct

dilation and a similar clinical presentation at onset [58–61].

Differentiating FAIP from adenocarcinoma is important to

avoid unnecessary surgical procedures. In both diseases,

the affected parenchyma appears hypovascular, hypodense

in the pancreatic phase (Figs. 3, 4) of the dynamic contrast-

enhanced MDCT study. The upstream MPD is frequently

dilated in adenocarcinoma. In FAIP, the upstream MPD

may be dilated, as in adenocarcinoma, but it may also be

normal. The latter finding is uncommon in patients with

adenocarcinoma. Therefore, in patients with enlarged

pancreatic head and normal size of upstream MPD, FAIP

should be considered in the differential diagnosis. In FAIP,

however, the hypodensity of the affected parenchyma

decreases in the venous and late phases (Fig. 3), unlike in

the case of adenocarcinoma (Fig. 4). The margins in FAIP

are more sharply defined than in adenocarcinoma, without

any extrapancreatic extension. The peripancreatic vessels

are normal. The presence of a capsule-like rim excludes

adenocarcinoma. Sometimes, the final diagnosis can only

be confirmed by a fine-needle aspiration biopsy [62].

AIP: MR and MRCP findings

MR imaging, especially completed by MRCP, with or

without secretin stimulation, is recommended for the

identification and characterisation of parenchymal and

ductal change in AIP.

At MR imaging, the pancreatic parenchyma shows dif-

fuse (Fig. 5) or focal (Fig. 6) enlargement with sharp

borders. It presents an abnormal signal intensity, usually

hypointense on T1-weighted images (Fig. 6a) and hyper-

intense on T2-weighted images, compared to the liver [63,

64]. On T2-weighted images, an hypointense capsule-like

rim may be present.

During the pancreatic phase of the dynamic study, the

parenchyma affected by AIP appears hypointense compared

to the spleen in diffuse forms (Fig. 5a, d) and to the unaf-

fected parenchyma in focal forms (Fig. 6b) [63]. In both

diffuse and focal forms of AIP, the affected parenchyma

usually appears hyperintense during the portal venous phase

(Figs. 5b, 6c) compared with the previous pancreatic phase

and it appears hyperintense in the delayed phase (Figs. 5c,

6d) compared with the venous phase, due to the contrast

medium retention, as in the MDCT study [63].

MRCP best depicts the pancreatic and biliary ductal

systems and it has a good correlation with the endoscopic

retrograde cholangiopancreatography (ERCP). The MPD is

typically not dilated and generally not visible within the

affected pancreatic parenchyma because of extrinsic com-

pression by the periductal cell infiltrate (Figs. 5, 6e). In the

focal forms, the MPD may present an upstream dilation

(Fig. 6e). MRCP after secretin stimulation can be useful to

better visualise the MPD. It is particularly important in the

focal forms, when a short ductal stricture can mimic a

malignant process. Secretin is a polypeptide hormone that

induces pancreatic bicarbonate-rich fluid secretion into the

duodenum and increases the tone of the sphincter of Oddi

with a temporary distension of the pancreatic ducts. If the

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Fig. 3 Focal autoimmune pancreatitis (FAIP). MDCT imaging.

Precontrast (a), contrast-enhanced pancreatic (b, d, e), venous (c,

f) phases. Axial (a–c, e) and multiplanar curved reconstruction (d,

f) MDCT images. Two cases (a–d, e, f). In the first case (a–d), the

MDCT images show focal enlargement of the pancreatic head. The

pancreatic parenchyma of the enlarged glandular portion (short

arrow) is homogeneously isodense to the spleen on precontrast

MDCT image (a). Pancreatic stones are absent. The pancreatic

parenchyma appears hypodense compared to the spleen and unaf-

fected adjacent parenchyma of the body-tail during the contrast-

enhanced MDCT pancreatic phase (b, d). During the portal venous

phase, the pancreatic parenchyma becomes more dense appearing

hyperdense compared to the attenuation of the previous pancreatic

phase (c). The intrahepatic bile ducts are dilated. The main pancreatic

duct is not visible within FAIP. Stenting of the upstream main

pancreatic duct was performed (arrows) to treat duct stenosis. A

nasogastric tube is present (arrow head). In the second case (e, f), the

MDCT images show focal enlargement of the pancreatic body and

tail. The parenchyma appears hypodense during the contrast-

enhanced MDCT pancreatic phase (e). The main pancreatic duct is

partially invisible because of focal ductal stenosis due to lympho-

plasmacytic infiltration and areas of fibrosis in the pancreatic body

and head, with upstream main duct dilatation. Enhancement of the

main duct walls is present (the enhanced duct sign: arrows). The

intrapancreatic segment of the common bile duct is slightly dilated

(arrow head)

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MPD stricture resolves after secretin stimulation, this rules

out a malignancy and is suggestive of AIP (the so-called

‘‘duct penetrating sign’’) [61]. Finally, MRCP is important

for evaluating the involvement of the biliary ducts, which

is frequently associated because the periductal infiltration

can extend to the intrapancreatic CBD and even to its su-

prapancreatic segment.

Recently, some authors [65–68] have reported that the

affected pancreatic parenchyma in both diffuse and focal

forms of AIP appears slightly hyperintense in the axial MR

DW images with b value = 600 s/mm2 and the baseline

ADC value is lower than the normal pancreatic paren-

chyma of patients without chronic pancreatitis (Fig. 5e, f).

It is possible that replacement of normal pancreatic

parenchyma with a severe inflammatory cellular infiltration

of lymphocytes, plasma cells and granulocytes, fibrous

tissue and/or reduced exocrine pancreatic function may

reduce diffusible tissue water and result in decreased

measured ADCs. Thus, in diffuse forms there is a diffusion

restriction at DWI and the ADC is low. In most instances,

diffusion restriction is not discernible because the entire

pancreatic gland is involved. When only a focal region is

involved this finding is more indicative. On the other hand,

DWI and ADC values are variable in pancreatic cancer,

allowing for this modality to differentiate between mass-

forming focal AIP and pancreatic carcinoma.

The final differential diagnosis between focal DAIP and

pancreatic cancer can only be confirmed by a fine-needle

aspiration biopsy [62, 69, 70].

Extrapancreatic AIP: MDCT and MR findings

CT and MR can identify some of the many extrapancreatic

manifestations of AIP, most commonly biliary, renal and

retroperitoneal [17, 71].

Biliary involvement, present in up to 80 % of AIP

patients, is the most common extrapancreatic involvement.

Both intrahepatic and extrahepatic bile ducts can be

involved, showing multifocal stenosis and wall thickening

Fig. 4 Focal autoimmune pancreatitis (FAIP): differential diagnosis

with pancreatic adenocarcinoma. MDCT imaging. Precontrast (a),

contrast-enhanced pancreatic (b), venous (c) and late (d) phases.

Axial MDCT images. MDCT images show focal enlargement of the

pancreatic head. The pancreatic head parenchyma is hypodense

compared to the spleen on precontrast MDCT images (a). The

pancreatic head lesion (short arrow) appears more hypodense

compared to the spleen and to the body-tail during pancreatic (b),

venous (c) and late (d) phases. The main pancreatic duct of the body-

tail (arrow) is dilated. The mesenteric vein lumen (arrow head) near

the solid lesion in the pancreatic head has a reduced diameter

(vascular infiltration)

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resembling primary sclerosing cholangitis. [72]. MDCT

shows only focal or diffuse thickening and enhancement of

bile duct wall. If the gallbladder is involved, it shows

diffuse wall thickening.

Biliary involvement by AIP is, therefore, best evaluated

by MRCP. This is an important technique to evaluate

involvement of the biliary ducts, which is frequently

associated because the periductal infiltration can extend to

the intrapancreatic CBD and even to its suprapancreatic

segment. This causes thickening and enhancement of the

CBD walls, a pattern similar to primary sclerosing cho-

langitis [73].

Renal involvement (Figs. 1, 6) is more rare than biliary

involvement (35 %). Renal lesions in AIP patients are

often multiple, bilateral cortex solid nodular lesions fre-

quently well circumscribed and well shaped. At MDCT

(Fig. 1) and MR imaging (Fig. 6), they appear as cortical

solid lesions, which are hypovascular during the pancreatic

Fig. 5 Diffuse autoimmune pancreatitis (DAIP). MR imaging. Axial

3D volumetric T1-weighted fat-suppressed gradient-echo images after

intravenous contrast medium administration during pancreatic (a),

venous (b) and delayed phase (c). Coronal true fast imaging in the

steady-state precession (true-FIST) (d). Diffusion-weighted MR

imaging (DWI): axial spin-echo echoplanar DW image with

b value = 600 s/mm2 (e); axial apparent diffusion coefficient

(ADC) map calculated from baseline images obtained with b value

of 0, 50, 600 (f). The overall pancreatic gland is enlarged with sharp

borders (a–d) and presents decreased enhancement in the arterial

pancreatic phase (a, d) compared to the spleen, with an increased

progressive contrast uptake during the venous (b) and the delayed

(c) phases. The affected pancreatic parenchyma appears slightly

hyperintense in the DW images (e) with lower ADC value (f) than

patients without pancreatitis due to a severe inflammatory cellular

infiltration (lymphocytes, plasma cells and granulocytes)

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phase of both modalities (Fig. 1b), with enhancement in

the venous (Fig. 1c) and delayed phases (Figs. 1d, 6f).

These lesions respond to steroid treatment with a reduction

in size.

Retroperitoneal involvement in AIP is represented by

retroperitoneal fibrosis. MDCT and MR identify a soft

tissue mass surrounding peripancreatic (Fig. 7a, b) and

retroperitoneal (Fig. 7d) vessels.

Fig. 6 Focal autoimmune pancreatitis (FAIP). MR imaging. Axial

3D volumetric T1-weighted fat-suppressed gradient-echo images

before (a) and after intravenous contrast medium administration

during the pancreatic (b), venous (c) and delayed phases (d, f). MR

cholangio-pancreatography (e). The parenchyma of the pancreatic

body-tail shows focal enlargement (arrows) with sharp borders and

abnormal signal intensity: it appears hypointense in the T1-weighted

images (a) compared to the unaffected parenchyma. In the dynamic

study, the AIP-affected parenchyma shows decreased enhancement

during the pancreatic phase (b), with a homogeneous and progressive

contrast uptake during the venous (c) and delayed phases (d). The

main pancreatic duct is not visible within the FAIP (e: arrowhead),

compressed by the crowded cellularity all around, with an upstream

dilation (e). This patient also presents renal involvement (f) with

multiple, bilateral, cortical solid lesions (black arrows: autoimmune

pyelonephritis)

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Post-treatment focal and diffuse AIP: MDCT and MR

findings

After a short-term treatment (2–3 weeks) with high-dose

steroid (Figs. 1f, 7e, f), MDCT and MR imaging can identify

a significant reduction in size of the pancreatic parenchyma

both in the diffuse and focal forms, as well as normalisation

of the calibre of the upstream MPD in the pancreatic head or

body of focal AIP [71]. Pancreatic enhancement during

MDCT and MR dynamic studies also becomes normal in

AIP. Both in diffuse and focal AIP, the pancreatic paren-

chyma appears isovascular to the spleen in the enhanced

Fig. 7 Extrapancreatic AIP findings. MDCT imaging. Contrast-

enhanced pancreatic (a–c, e), venous (d, f) phases. Axial (a, c–

f) and multiplanar coronal reconstruction (b). Two cases (a, b, c–f). In

both cases (a, b, c–f), diffuse pancreatic enlargement and hypodense

pancreatic parenchyma are present during the pancreatic phase.

MDCT also shows a retroperitoneal soft tissue mass surrounding

peripancreatic vessels (a, b: arrows) and right side pelvic vessels (d:

arrow). Histological analysis of pancreatic, retroperitoneal and pelvic

soft tissue mass showed lymphoplasmacytic infiltrate and fibrosis. In

the second case, the pancreatic parenchyma (e) and pelvic soft tissue

mass (f: arrow) are reduced in size at follow-up CT 3 weeks after

high-dose steroid treatment

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pancreatic phase and hypovascular in the venous phase, with

wash-out in the delayed phase. Finally, MDCT and MR

imaging can easily identify normalisation of the calibre of

the intra- and suprapancreatic common bile duct [19, 20, 37].

The Japan Pancreas Society has proposed diagnostic cri-

teria for the diagnosis of AIP [74–78]. These criteria include:

the finding of typical pancreatic imaging results (enlargement

of the pancreatic parenchyma and MPD narrowing), positive

laboratory tests (autoantibodies and elevated serum levels of

immunoglobulin G4) and positive histopathologic al findings

(lymphoplasmacytic infiltrate and pancreatic fibrosis). When

all three diagnostic criteria proposed by the Japan Pancreas

Society are present, AIP diagnosis is easy. However, there are

clinical conditions in which AIP diagnosis and the differential

diagnosis with other pancreatic diseases may be difficult. The

differential diagnosis of AIP is difficult when a patient with

typical clinical findings has other associated autoimmune

disorders with only non-specific imaging and/or histopathol-

ogical findings. In all the cases in which AIP is strongly sus-

pected but the diagnosis is uncertain, MDCT and MR are

useful imaging modalities to suggest the correct diagnosis.

Repeated MDCT and/or MR examinations after short-term

treatment (2–3 weeks) with high-dose steroids can identify a

significant reduction in the size of pancreatic parenchyma, and

the normalisation of the calibre of the MPD and bile ducts. The

results of this short-term follow-up are obviously present in

AIP and absent in the case of pancreatic adenocarcinoma. The

response at short-term imaging follow-up after steroid treat-

ment was recently considered a diagnostic criterion of AIP [1].

Conflict of interest RGraziani, S. Mautone, M.C. Ambrosetti, R.

Manfredi, T.J. Re, L. Calculli, L. Frulloni, R. Pozzi Mucelli declare

no conflict of interest.

References

1. Shimosegawa T, Chari ST, Frulloni L, Kamisawa T, Kawa S,

Mino-Kenudson M, Kim MH, Kloppel G, Lerch MM, Lohr M,

Notohara K, Okazaki K, Schneider A, Zhang L, International

Association of Pancreatology (2011) International consensus

diagnostic criteria for autoimmune pancreatitis: guidelines of the

International Association of Pancreatology. Pancreas 40:352–358

2. Kamisawa T, Egawa N, Nakajima H (2003) Autoimmune pan-

creatitis is a systemic autoimmune disease. Am J Gastroenterol

98:2811–2812

3. Zhang L, Notohara K, Levy MJ et al (2007) IgG4-positive plasma

cell infiltration in the diagnosis of autoimmune pancreatitis. Mod

Pathol 20:23–28

4. Cavallini G (1993) Is chronic pancreatitis a primary disease of the

pancreatic ducts? A new pathogenetic hypothesis. Ital J Gastro-

enterol 25:391–396

5. Yoshida K, Toki F, Takeuchi T et al (1995) Chronic pancreatitis

caused by an autoimmune abnormality. Proposal of the concept

of autoimmune pancreatitis. Dig Dis Sci 40:1561–1568

6. Okazaki K (2001) Autoimmune-related pancreatitis. Curr Treat

Options Gastroenterol 4:369–375

7. Sjogren I, Wengle B, Korsgren M (1979) Primary sclerosing

cholangitis associated with fibrosis of the submandibular glands

and the pancreas. Acta Med Scand 205:139–141

8. Gelrud A, Freedman SD (2005) Autoimmune pancreatitis.

J Gastrointest Surg 9:2–5

9. Ketikoglou I, Moulakakis A (2005) Autoimmune pancreatitis.

Dig Liver Dis 37:211–215

10. Frulloni L, Bovo P, Di Francesco V et al (1999) ‘‘Non-alcoholic

duct destructive chronic pancreatitis’’ or ‘‘primary chronic pan-

creatitis’’? Gut 44:579

11. Montefusco PP, Geiss AC, Bronzo RL et al (1984) Sclerosing

cholangitis, chronic pancreatitis, and Sjogren’s syndrome: a

syndrome complex. Am J Surg 147:822–826

12. Kloppel G, Luttges J, Lohr M et al (2003) Autoimmune pan-

creatitis: pathological, clinical, and immunological features.

Pancreas 27:14–19

13. Zamboni G, Luttges J, Capelli P et al (2004) Histopathological

features of diagnostic and clinical relevance in autoimmune

pancreatitis: a study on 53 resection specimens and 9 biopsy

specimens. Virchows Arch 445:552–563

14. Ghazale AH, Chari ST, Vege SS (2008) Update on the diagnosis

and treatment of autoimmune pancreatitis. Curr Gastroenterol

Rep 10:115–121

15. Toomey DP, Swan N, Torreggiani W, Conlon KC (2007) Auto-

immune pancreatitis. Br J Surg 94:1067–1074

16. Cavallini G, Frulloni L, Bassi C et al (2004) Prospective multi-

centre survey on acute pancreatitis in Italy (ProInf AISP): results

on 1005 patients. Dig Liver Dis 36:205–211

17. Bodily KD, Takahashi N, Fletcher JG et al (2009) Autoimmune

pancreatitis: pancreatic and extrapancreatic imaging finding. Am

J Roentgenol 192:431–437

18. Kawa S, Hamanno H, Umemura T et al (2007) Sclerosing cho-

langitis associated with autoimmune pancreatitis. Hepatol Res

37:S487–S495

19. Bollen TL, van Santvoort HC, Besselink MG et al (2008) The

Atlanta classification of acute pancreatitis revisited. Br J Surg

95:6–21

20. Frulloni L, Scattolini C, Falconi M et al (2009) Autoimmune

pancreatitis: differences between the focal and diffuse forms in

87 patients. Am J Gastroenterol 104:2288–2294

21. Kim KP, Kim MH, Song MH et al (2004) Autoimmune chronic

pancreatitis. Am J Gastroenterol 99:1605–1616

22. Procacci C, Carbognin G, Biasiutti C et al (2001) Autoimmune

pancreatitis: possibilities of CT characterization. Pancreatology

1:246–253

23. Sahani DV, Kalva SP, Farrell J et al (2004) Autoimmune pan-

creatitis: imaging features. Radiology 233:345–352

24. Yang DH, Kim KW, Kim TK (2006) Autoimmune pancreatitis:

radiologic findings in 20 patients. Abdom Imaging 31:94–102

25. Balthazar EJ (2002) Acute pancreatitis: assessment of severity

with clinical and CT evaluation. Radiology 223:603–613

26. Okazaki K, Kawa S, Kamisawa T (2006) Clinical diagnostic

criteria of autoimmune pancreatitis: revised proposal. J Gastro-

enterol 41:626–631

27. Desiree EM (2008) Imaging of acute pancreatitis and its com-

plications. Clin Gastroenterol Hepatol 6:1077–1085

28. Kwon S, Kim MH, Choi EK (2007) The diagnostic criteria for

autoimmune chronic pancreatitis: it is time to make a consensus.

Pancreas 34:279–286

29. Nakazawa T, Ohara H, Sano H (2007) Difficulty in diagnosing

autoimmune pancreatitis by imaging findings. Gastrointest En-

dosc 65:99–108

30. Kamisawa T (2008) Diagnostic criteria for autoimmune pancre-

atitis. J Clin Gastroenterol 42:404–407

31. Graziani R, Cenci D, Franzoso F (2009) The role of computed

tomography. In: Balthazar EJ, Megibow AJ, Pozzi Mucelli R

Radiol med

123

(eds) Imaging of the pancreas. Springer Berlin Heidelberg, Ber-

lin, pp 149–183

32. Graziani R, Cicero C, Casagranda G et al (2008) Pancreatite

cronica. In: Graziani R, Pozzi Mucelli R (eds) TC multistrato del

pancreas. Idelson Gnocchi, Sorbona, pp 45–84

33. Graziani R, Cicero C, Casagranda G (2008) Pancreas. In: Pozzi

Mucelli R (ed) TC multistrato addome. Idelson Gnocchi, Sor-

bona, pp 193–262

34. Horiuchi A, Kaneko T, Yamamura N et al (1996) Autoimmune

chronic pancreatitis simulating pancreatic lymphoma. Am J

Gastroenterol 911:2607–2609

35. Irie H, Honda H, Baba S et al (1998) Autoimmune pancreatitis: CT

and MR characteristics. AJR Am J Roentgenol 170:1323–1327

36. Eerens I, Vanbeckevoort D, Vansteenbergen W, Van Hoe L (2001)

Autoimmune pancreatitis associated with primary sclerosing

cholangitis: MR imaging findings. Eur Radiol 11:1401–1404

37. Manfredi R, Graziani R, Cicero C et al (2008) Autoimmune

pancreatitis: CT patterns and their changes after steroid treatment.

Radiology 247:435–443

38. Takayama M, Hamano H, Ochi Y et al (2004) Recurrent attacks

of autoimmune pancreatitis result in pancreatic stone formation.

Am J Gastroenterol 99:932–937

39. Takahashi N, Fletcher JG, Hough DM et al (2009) Autoimmune

pancreatitis: differentiation from pancreatic carcinoma and nor-

mal pancreas on the basis of enhancement characteristics at dual-

phase CT. AJR Am J Roentgenol 193:479–484

40. Sugumar A, Chari ST (2011) Autoimmune pancreatitis. J Gas-

troenterol Hepatol 26:1368–1373 (Review)

41. Okazaki K, Kawa S, Kamisawa T, Shimosegawa T, Tanaka M,

Research Committee for Intractable Pancreatic Disease and Japan

Pancreas Society (2010) Japanese consensus guidelines for

management of autoimmune pancreatitis: I. Concept and diag-

nosis of autoimmune pancreatitis. J Gastroenterol 45:249–265

42. Suzuki K, Itoh S, Nagasaka T et al (2010) CT findings in auto-

immune pancreatitis: assessment using multiphase contrast-

enhanced multisection CT. Clin Radiol 65:735–743

43. Kawai Y, Suzuki K, Itoh S et al (2012) Autoimmune pancreatitis:

assessment of the enhanced duct sign on multiphase contrast-

enhanced computed tomography. Eur J Radiol 81:3055–3060

44. Klimstra DS, Adsay NV (2004) Lymphoplasmacytic sclerosing

(autoimmune) pancreatitis. Semin Diagn Pathol 21:237–246

45. Ito T, Nakano I, Koyanagi S et al (1997) Autoimmune pancrea-

titis as a new clinical entity: three cases of autoimmune pancre-

atitis with effective steroid therapy. Dig Dis Sci 42:1458–1468

46. Kamisawa T, Tu Y, Egawa N et al (2006) Involvement of pan-

creatic and bile ducts in autoimmune pancreatitis. World J Gas-

troenterol 28:612–614

47. Van Hoe L, Gryspeerdt S, Ectors N et al (1998) Nonalcholic duct-

destructive chronic pancreatitis: imaging findings. AJR Am J

Roentgenol 170:643–647

48. Kawamoto S, Siegelman SS, Hruban RH, Fishman EK (2008)

Lymphoplasmacytic sclerosing pancreatitis (autoimmune pan-

creatitis): evolution with multidetector CT. Radiographics

28:157–170

49. Furukawa N, Muranaka T, Yasumori K et al (1998) Autoimmune

pancreatitis: radiologic findings in three histologically proven

cases. J Comput Assist Tomogr 22:880–883

50. Graziani R, Frulloni L, Mantovani W et al (2012) Autoimmune

pancreatitis and non-necrotizing acute pancreatitis: computed

tomography pattern. Dig Liver Dis 44:759–766

51. Webb TH, Lillemoe KD, Pitt HA et al (1989) Pancreatic lym-

phoma. Is surgery mandatory for diagnosis or treatment? Ann

Surg 209:25–30

52. Glazer HS, Lee KJ, Balfe DM et al (1983) Non-Hodgkin lym-

phoma: computed tomographic demonstration of unusual ex-

tranodal involvement. Radiology 149:211–217

53. Sahani DV, Sainani NI, Deshpande V et al (2009) Autoimmune

pancreatitis: disease evolution, staging, response, assessment and

CT features that predict response to corticosteroid therapy.

Radiology 250:118–129

54. Van Beers B, Lalonde L, Soyer P et al (1993) Dynamic CT in

pancreatic lymphoma. J Comput Assist Tomogr 17:94–97

55. Ferrozzi F, Zuccoli G, Bova D, Calculli L (2000) Tumori mes-

enchimali del pancreas: aspetti con tomografia computerizzata.

J Comput Assist Tomogr 24:622–627

56. Sheth S, Fishman EK (2002) Imaging of uncommon tumors of

the pancreas. Radiol Clin North Am 40:1273–1287

57. Muhi A, Ichikawa T, Motosugi U et al (2012) Mass-forming

autoimmune pancreatitis and pancreatic carcinoma: differential

diagnosis on the basis of computed tomography and magnetic

resonance cholangiopancreatography, and diffusion-weighted

imaging findings. J Magn Reson Imaging 35:827–836

58. Triantopoulou C, Giannakou N, Delis S et al (2007) Focal lym-

phoplasmacytic sclerosing pancreatitis. Pancreas 35:180–186

59. Wakabayashi T, Kawaura Y, Satomura Y et al (2003) Clinical

and imaging features of autoimmune pancreatitis with focal

pancreatic swelling or mass formation: comparison with so-called

tumor forming pancreatitis and pancreatic carcinoma. Am J

Gastroenterol 98:2679–2687

60. Wakabayashi T, Kawaura Y, Satomura Y et al (2002) Clinical

study of chronic pancreatitis with focal irregular narrowing of the

main pancreatic duct and mass formation. Comparison with

chronic pancreatitis showing diffuse irregular narrowing of the

main pancreatic duct. Pancreas 25:283–289

61. Ichikawa T, Sou H, Araki T et al (2001) Duct-penetrating sign at

MRCP: usefulness for differentiating inflammatory pancreatic

mass from pancreatic carcinomas. Radiology 221:107–116

62. Levy MJ, Wiersema MJ, Chari ST (2006) Chronic pancreatitis:

focal pancreatitis or cancer? Is there a role for FNA/biopsy?

Autoimmune pancreatitis. Endoscopy 38:S30–S35

63. Manfredi R, Frulloni L, Mantovani W et al (2011) Autoimmune

pancreatitis: pancreatic and extrapancreatic MR imaging-MR

cholangiopancreatography findings at diagnosis, after steroid

therapy, and at recurrence. Radiology 260:428–436

64. Balci NC, Bieneman BK, Bilgin M et al (2009) Magnetic reso-

nance imaging in pancreatitis. Top Magn Reson Imaging

20:25–30 (review)

65. Akisik MF, Aisen AM, Sandrasegaran K et al (2009) Assessment

of chronic pancreatitis: utility of diffusion-weighted MR imaging

with secretin enhancement. Radiology 250:103–109

66. Erturk SM, Ichikawa T, Motosugi U et al (2006) Diffusion-

weighted MR imaging in the evaluation of pancreatic exocrine

function before and after secretin stimulation. Am J Gastroenterol

101:133–136

67. Taniguchi T, Kobayashi H, Nishikawa K et al (2009) Diffusion-

weighted magnetic resonance imaging in autoimmune pancrea-

titis. Jpn J Radiol 27:138–142

68. Kamisawa T, Takuma K, Anjiki H et al (2010) Differentiation of

autoimmune pancreatitis from pancreatic cancer by diffusion-

weighted MRI. Am J Gastroenterol 105:1870–1875

69. Choueiri NE, Balci NC, Alkaade S, Burton FR (2010) Advanced

imaging of chronic pancreatitis. Curr Gastroenterol Rep 12:114–120

70. Braganza JM, Lee SH, McCloy RF, McMahon MJ (2011)

Chronic pancreatitis. Lancet 377:1184–1197

71. Church NI, Pereira SP, Deheragoda MG et al (2007) Autoim-

mune pancreatitis: clinical and radiological features and objective

response to steroid therapy in a UK series. Am J Gastroenterol

102:2417–2425

72. Maeda E, Akahane M, Yoshioka N et al (2012) Comparison of

CT findings of biliary tract changes with autoimmune pancreatitis

and extrahepatic bile duct cholangiocarcinoma. Jpn J Radiol

30:227–234

Radiol med

123

73. Nishino T, Toki F, Oyama H et al (2005) Biliary tract involve-

ment in autoimmune pancreatitis. Pancreas 30:76–82

74. Members of the Criteria Committee for Autoimmune Pancreatitis

of the Japan Pancreas Society (2002) Diagnostic criteria for auto-

immune pancreatitis by the Japan Pancreas Society. J Jpn Pancreas

17:587

75. Okazaki K (2005) Autoimmune pancreatitis: etiology, patho-

genesis, clinical findings and treatment: the Japanese experience.

JOP 6:89–96

76. Chari ST, Smyrk TC, Levy MJ et al (2006) Diagnosis of auto-

immune pancreatitis: the Mayo Clinic experience. Clin Gastro-

enterol Hepatol 4:1010–1016

77. Choi EK, Kim MH, Kim JC et al (2006) The Japanese diagnostic

criteria for autoimmune chronic pancreatitis: is it completely

satisfactory? Pancreas 33:13–19

78. Kim KP, Kim MH, Kim JC et al (2006) Diagnostic criteria for

autoimmune chronic pancreatitis revisited. World J Gastroenterol

28:2487–2496

Radiol med

123