IPMN: is het nu kanker of niet?

Gastroenterologische oncologische zorg Nieuwe ontwikkelingen, nieuwe zorg(en)? IPMN: is het nu kanker of niet? dr. Jeanin van Hooft MDL-­‐arts, AMC Amsterdam IPMN: is het nu kanker of niet?
•  How it came into the picture
•  Different types
•  Unraveling IPMN
•  Daily practice
•  Summary
•  Take home
IPMN: is het nu kanker of niet?
How it came into the picture
IPMN: is het nu kanker of niet?
How it came into the picture
• IPMN
• Intraductal
• Papillary
• Mucinous
• Neoplasm
IPMN: is het nu kanker of niet?
How it came into the picture
•  1982 first described as mucinproducing tumor
•  1996 formal recognition by the WHO
as IPMN
•  2006 first guide
line
Ohashi K et al., Prog Dig Endosc. 1982
IPMN: is het nu kanker of niet?
How it came into the picture
• Cross sectional modalities
•  1965 real-time ultrasound Vidoson® by Siemens
Medical Systems, Germany
•  1971 clinical CT scan EMI Research
Laboratories, London
•  5 min per slide
IPMN: is het nu kanker of niet?
How
it came into
the picture
Why are
we particularly
interested
in CT?
USA
0.2
50
0.15
40
30
0.1
20
0.05
10
0
0
1980
1985
1990
1995
2000
2005
Year
http://en.wikipedia.org/wiki/X-ray_computed_tomography
3.0
UK
0.05
2.5
0.04
2.0
0.03
1.5
0.02
1.0
0.01
0.5
0.0
0
1980
1985
1990
1995
Year
2000
2005
Number of CT scans per person / year
60
CT scans per year in the UK (millions)
0.25
70
Number of CT scans per person / year
CT scans per year in US (millions)
•  70 million
CTs ofper
1 out
Frequency
CT year,
scans per
yearof 4
IPMN: is het nu kanker of niet?
How it came into the picture
Incidence of total
IPMN
Klibansky et al., Clin Gastroenterol Hepatol 2012
IPMN: is het nu kanker of niet?
Different types
IPMN: is het nu kanker of niet?
Different types
•  Based on location:
•  Branch duct IPMN
•  Main duct IPMN
•  Mixed IPMN
IPMN: is het nu kanker of niet?
Different types
•  Based on cellular atypia:
•  Benign (low-grade dysplasia)
•  Borderline (intermediate & high grade)
•  Malignant (cancer)
IPMN: is het nu kanker of niet?
Different types
•  Different types, different behaviour
•  Prevalence of malignancy
•  Main duct IPMN 57-92%
•  Side branch IPMN 6-46%
•  Malignancy at 5 years
•  Main duct IPMN 63%
•  Side branch IPMN 15%
De Jong et al., Gastroenterol Res Pract 2012
Sahani et al., Clin Gastroent Hepatol 2009
IPMN: is het nu kanker of niet?
Unraveling IPMN
•  http:/
IPMN: is het nu kanker of niet?
Unraveling IPMN
• Anamnesis (ao pancreatitis, symptoms
suspicious for malignancy)
• High quality imaging studies
•  CT scan
•  Solid masses
•  Calcifications
•  MRI scan
•  Cysts
•  Connection PD
IPMN: is het nu kanker of niet?
Unraveling IPMN
• High risk stigmata
• 
• 
Enhanced solid component
Main duct ≥ 10 mm
• Worrisome features
• 
• 
• 
• 
• 
• 
Cyst ≥ 3 cm
Thickened cyst wall
Non-enhanced nodules
Main duct 5-9 mm
Abrupt change in main duct
Lymphadenopathy
3. Investigation
IPMN:
is het
nu kanker
of niet?
3.1. Work-up for cystic
lesions
of the
pancreas
Unraveling
IPMN
Cystic lesions are increasingly being recognized by imaging
he
un
“w
str
fea
thi
eld
studies, and the frequency of pancreatic cyst detection by MRI
(19.9% [28]) is higher than by CT (1.2% [29] and 2.6% [30]). A cyst
Contents lists
at SciVerse ScienceDirect
with invasive carcinoma
isavailable
uncommon
in patients with an
asymptomatic pancreatic cyst,
particularly one of <10 mm in size,
fea
Pancreatology
and therefore no further work-up may be needed at that point,
cat
journal homepage: www.elsevier.com/locate/pan
although follow-up is still recommended [31,32]. For cysts greater
than
1 cm, pancreatic protocol CT or gadolinium-enhanced
MRI
Review article
3.2
Pancreatology 12 (2012) 183e197
with
magnetic
resonance
(MRCP)
International
consensus
guidelinescholangiopancreatography
2012 for the management of IPMN
and MCNisof
the pancreas
recommended
for better characterization
of the
(Fig.
2) [33]. ScienceD
Contents
listslesion
available
at SciVerse
a, *
e
Masao
Tanakaconsensus
, Carlos Fernández-del
Castillo b, Volkan
Adsay c, Suresh
Chari d, Massimo
Falconi
,
A
recent
of
radiologists
suggested
dedicated
MRI
as
the
act
f
g
h
i
j
Jin-Young Jang , Wataru Kimura , Philippe Levy , Martha Bishop Pitman , C. Max Schmidt ,
l
m
n
procedure
choice L.for
evaluating
a pancreatic
cyst,
based on its
no
, Christopher
Wolfgang
, Koji Yamaguchi
, Kenji Yamao
Michio Shimizu kof
Pancreatology
superior contrast resolution that facilitates recognition of septae,
on
nodules, and duct communications [33]. When patients are
acc
journal homepage: www.elsevier.com/lo
required to undergo frequent imaging for follow-up, MRI may be
na
Berlandfor
et al.,avoiding
J Am Col Radiol
2010
better
radiation
exposure.
ini
Waters et al., J Gastrointest Surg 2008
Review
article
For amelioration
of symptoms, and owing to the higher risk of
im
Pancreatology 12 (2012) 183e197
•  CT vs MRI/MRCP for pancreatic cyst
analysis
•  No high grade evidence
a
Department of Surgery and Oncology, Graduate School of Medical Sciences, Kyushu University, Fukuoka 812-8582, Japan
Pancreas and Biliary Surgery Program, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA
c
Department of Anatomic Pathology, Emory University Hospital, Atlanta, GA, USA
d
Pancreas Interest Group, Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN, USA
e
U.O. Chirurgia B, Dipartimento di Chirurgia Policlinico “G.B. Rossi”, Verona, Italy
f
Division of Hepatobiliary-Pancreatic Surgery, Department of Surgery, Seoul National University College of Medicine, Seoul, South Korea
g
First Department of Surgery, Yamagata University, Yamagata, Japan
h
Pôle des Maladies de l’Appareil Digestif, Service de Gastroentérologie-Pancréatologie, Hopital Beaujon, Clichy Cedex, France
i
Department of Pathology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA
j
Department of Surgery, Indiana University, Indianapolis, IN, USA
k
Department of Pathology, Saitama Medical University, International Medical Center, Saitama, Japan
l
Cameron Division of Surgical Oncology and The Sol Goldman Pancreatic Cancer Research Center, Department of Surgery, Johns Hopkins University, Baltimore, MD, USA
b
m
IPMN: is het nu kanker of niet?
Unraveling IPMN
•  Role of EUS
•  Very high spatial resolution
• 
• 
• 
Solid masses
Vascular invasion
Lympnode metastases
•  FNA
• 
• 
• 
Viscosity
Biochemistry
Cytology
IPMN: is het nu kanker of niet?
Unraveling IPMN
•  Limitations of EUS
•  FNA complications (pancreatitis)
•  Invasive
•  Operator depending
Hutchins et al., Surg Clin N Am 2010
Tanaka et al., Pancreatology 2012
IPMN: is het nu kanker of niet?
Daily practice
IPMN: is het nu kanker of niet?
Daily practice
• ♂ 78
•  Extensive cardiac, pulmonary and
urologic history
•  No complaints
•  Imaging as FU for bladder cancer
IPMN: is het nu kanker of niet?
Daily practice
!
Report:!
“Dilated PD up to 8 mm, with
focal cyst of 3 cm”!
IPMN: is het nu kanker of niet?
Daily practice
!
What would you do?
•  Review images?
•  Conduct EUS?
•  FNA?
alignancy, all symptomatic cysts should be further evaluated or
sected as determined by the clinical circumstances.
“Worrisome features” on imaging include cyst of !3 cm, thickned enhanced cyst walls, MPD size of 5e9 mm, non-enhanced
ural nodules, abrupt change in the MPD caliber with distal
ancreatic atrophy, and lymphadenopathy [34e38].
Cysts with obvious “high-risk stigmata” on CT or MRI (i.e.,
bstructive jaundice in a patient with a cystic lesion of the pancreatic
are the most useful primary methods for defining the mor
location, multiplicity, and communication with the
[8,9,18,57,58]. Reliable distinguishing features of BD-IPMN
multiplicity and visualization of a connection to the MPD, a
such a connection is not always observed. EUS can then be
detecting mural nodules and invasion, and is most effe
delineating the malignant characteristics (Fig. 3) [18], alth
has the limitation of operator dependency [13,58]. C
IPMN: is het nu kanker of niet?
Daily practice
!
Are any of the following high-risk stigmata of malignancy present?
i) obstructive jaundice in a patient with cystic lesion of the head of the pancreas, ii) enhancing solid component within cyst,
iii) main pancreatic duct >10 mm in size
Yes
No
Are any of the following worrisome features present?
Clinical: Pancreatitis a
Imaging: i) cyst >3 cm, ii) thickened/enhancing cyst walls, iii) main duct size 5-9 mm, iii) non-enhancing
mural nodule iv) abrupt change in caliber of pancreatic duct with distal pancreatic atrophy.
Consider
surgery,
if clinically
appropriate
No
If yes, perform endoscopic ultrasound
Are any of these features present?
No
i) Definite mural nodule (s)b
Yes
ii) Main duct features suspicious for involvement c
iii) Cytology: suspicious or positive for malignancy
Inconclusive
<1 cm
1-2 cm
2-3 cm
CT/MRI
CT/MRI
yearly x 2 years,
then lengthen
interval
if no change d
EUS in 3-6 months, then
lengthen interval alternating MRI
with EUS as appropriate. d
Consider surgery in young,
fit patients with need for
prolonged surveillance
in 2-3 years d
What is the size of largest cyst?
Tanaka et al., Pancreatology 2012
a. Pancreatitis may be an indication for surgery for relief of symptoms.
>3 cm
Close surveillance alternating
MRI with EUS every 3-6 months.
Strongly consider surgery in young,
fit patients
mptomatic cysts should be further evaluated or
ined by the clinical circumstances.
is het
nu
ures” on imaging include cyst IPMN:
of !3 cm,
thickst walls, MPD size of 5e9 mm, non-enhanced
rupt change in the MPD caliber with distal
and lymphadenopathy [34e38].
ious “high-risk stigmata” on CT or MRI (i.e.,
e in a patient with a cystic lesion of the pancreatic
are the most useful primary methods for defin
location, multiplicity, and communication
kanker
of niet?Reliable distinguishing features
[8,9,18,57,58].
multiplicity and visualization of a connection t
such a connection is not always observed. EUS
detecting mural nodules and invasion, and
delineating the malignant characteristics (Fig
has the limitation of operator dependenc
Daily practice
!
Are any of the following high-risk stigmata of malignancy present?
i) obstructive jaundice in a patient with cystic lesion of the head of the pancreas, ii) enhancing solid component within cyst,
iii) main pancreatic duct >10 mm in size
Yes
Consider
surgery,
if clinically
appropriate
No
Are any of the following worrisome features present?
Clinical: Pancreatitis a
Imaging: i) cyst >3 cm, ii) thickened/enhancing cyst walls, iii) main duct size 5-9 mm, iii) non-enhancing
mural nodule iv) abrupt change in caliber of pancreatic duct with distal pancreatic atrophy.
No
If yes, perform endoscopic ultrasound
Are any of these features present?
Yes
i) Definite mural nodule (s)b
ii) Main duct features suspicious for involvement c
iii) Cytology: suspicious or positive for malignancy
No
What is the size of largest cyst?
Inconclusive
IPMN: is het nu kanker of niet?
Daily practice
!
•  Conduct EUS
•  Mural nodes?
•  Main duct involved?
•  Obtain cytology
IPMN: is het nu kanker of niet?
Daily practice
!
• Conclusion
•  IPMN, fish eye
•  Main duct involved, 3 cm Ø
•  Cytology suspicious for malignancy
•  Main duct IPMN
Because of clinical condition operation
sustained
IPMN: is het nu kanker of niet?
Daily practice
• ♀ 65
•  Unremarkable history
•  No complaints
•  Check up “for safety”
• 
MRI revealed pancreatic cyst
IPMN: is het nu kanker of niet?
Daily practice
!
Report:!
“One cystic lesion close to PD
in body of pancreas, roughly 3
cm”!
mptomatic cysts should be further evaluated or
ined by the clinical circumstances.
is het
nu
ures” on imaging include cyst IPMN:
of !3 cm,
thickst walls, MPD size of 5e9 mm, non-enhanced
rupt change in the MPD caliber with distal
and lymphadenopathy [34e38].
ious “high-risk stigmata” on CT or MRI (i.e.,
e in a patient with a cystic lesion of the pancreatic
are the most useful primary methods for defin
location, multiplicity, and communication
kanker
of niet?Reliable distinguishing features
[8,9,18,57,58].
multiplicity and visualization of a connection t
such a connection is not always observed. EUS
detecting mural nodules and invasion, and
delineating the malignant characteristics (Fig
has the limitation of operator dependenc
Daily practice
!
Are any of the following high-risk stigmata of malignancy present?
i) obstructive jaundice in a patient with cystic lesion of the head of the pancreas, ii) enhancing solid component within cyst,
iii) main pancreatic duct >10 mm in size
Yes
Consider
surgery,
if clinically
appropriate
No
Are any of the following worrisome features present?
Clinical: Pancreatitis a
Imaging: i) cyst >3 cm, ii) thickened/enhancing cyst walls, iii) main duct size 5-9 mm, iii) non-enhancing
mural nodule iv) abrupt change in caliber of pancreatic duct with distal pancreatic atrophy.
No
If yes, perform endoscopic ultrasound
Are any of these features present?
Yes
i) Definite mural nodule (s)b
ii) Main duct features suspicious for involvement c
iii) Cytology: suspicious or positive for malignancy
No
What is the size of largest cyst?
Inconclusive
IPMN: is het nu kanker of niet?
Daily practice
!
IPMN: is het nu kanker of niet?
Daily practice
!
• Conclusion
•  2 cm cyst, relation with PD, main duct
not involved
•  FNA
•  Mucous
•  CEA 820 ng/ml
•  Amylase 4000 u/l
•  Branch duct IPMN
alignancy, all symptomatic cysts should be further evaluated or
sected as determined by the clinical circumstances.
“Worrisome features” on imaging include cyst of !3 cm, thickned enhanced cyst walls, MPD size of 5e9 mm, non-enhanced
ural nodules, abrupt change in the MPD caliber with distal
ancreatic atrophy, and lymphadenopathy [34e38].
Cysts with obvious “high-risk stigmata” on CT or MRI (i.e.,
bstructive jaundice in a patient with a cystic lesion of the pancreatic
are the most useful primary methods for defining the mor
location, multiplicity, and communication with the
[8,9,18,57,58]. Reliable distinguishing features of BD-IPMN
multiplicity and visualization of a connection to the MPD, a
such a connection is not always observed. EUS can then be
detecting mural nodules and invasion, and is most effe
delineating the malignant characteristics (Fig. 3) [18], alth
has the limitation of operator dependency [13,58]. C
IPMN: is het nu kanker of niet?
Daily practice
!
Are any of the following high-risk stigmata of malignancy present?
i) obstructive jaundice in a patient with cystic lesion of the head of the pancreas, ii) enhancing solid component within cyst,
iii) main pancreatic duct >10 mm in size
Yes
No
Are any of the following worrisome features present?
Clinical: Pancreatitis a
Imaging: i) cyst >3 cm, ii) thickened/enhancing cyst walls, iii) main duct size 5-9 mm, iii) non-enhancing
mural nodule iv) abrupt change in caliber of pancreatic duct with distal pancreatic atrophy.
Consider
surgery,
if clinically
appropriate
No
If yes, perform endoscopic ultrasound
Are any of these features present?
No
i) Definite mural nodule (s)b
Yes
ii) Main duct features suspicious for involvement c
iii) Cytology: suspicious or positive for malignancy
Inconclusive
<1 cm
1-2 cm
2-3 cm
CT/MRI
CT/MRI
yearly x 2 years,
then lengthen
interval
if no change d
EUS in 3-6 months, then
lengthen interval alternating MRI
with EUS as appropriate. d
Consider surgery in young,
fit patients with need for
prolonged surveillance
in 2-3 years d
What is the size of largest cyst?
Tanaka et al., Pancreatology 2012
a. Pancreatitis may be an indication for surgery for relief of symptoms.
>3 cm
Close surveillance alternating
MRI with EUS every 3-6 months.
Strongly consider surgery in young,
fit patients
IPMN: is het nu kanker of niet?
Summary
IPMN: is het nu kanker of niet?
Summary
!
• 
• 
• 
• 
• 
Fast rising incidence
Different types
CT/MRI for initial screening
EUS/EUS-FNA on indication
High risk stigmata/worrisome features?
RESECT
•  Close follow-up
IPMN: is het nu kanker of niet?
Take home
!
IPMN
Malignant potency
Different types
Different risks