Medical Management of

Pancreatic Cysts

Jeffrey H. Lee, MD, MPH, FACG, FASGE, AGAF

Professor and Director, Advanced Endoscopy

Fellowship and Training
MD Anderson Cancer Center
Pancreatic Cystic Lesions (PCLs)
1. Non-neoplastic pancreatic cysts
Pseudocyst
Congenital cyst
Retention cyst
2. Neoplastic pancreatic cysts (pancreatic cystic neoplasms)
Mucinous cystic lesions
Intraductal papillary mucinous neoplasm (IPMN)
Mucinous cystic neoplasm (MCN)
Non-mucinous cystic lesions
Serous cystic neoplasm (SCN)
Solid-pseudopapillary neoplasm (SPN)
Cystic neuroendocrine neoplasm
Acinar-cell cystic neoplasm
Ductal adenocarcinoma with cystic degeneration
Pancreatic Cystic Neoplasms (PCNs)

Prevalence
Imaging-based studies: 1.2% - 1.9%
In autopsy series of 300 patients
186 cystic lesions in 73 of 300 patients
(24.3%)
Increases with age

Yoon et al. Clin North Am 1012

Laffan et al. Am J Roentgenol 2008
 WHO Classification of PCNs
Benign
Serous Cystadenoma (SCN)
Premalignant
IPMN with low- or intermediate-grade dysplasia
IPMN with high grade dysplasia
Mucinous cystic neoplasm (MCN) with low- or intermediate-
grade dysplasia
Mucinous cystic neoplasm (MCN) with high-grade dysplasia
Malignant
Mucinous cystadenocarcinoma
IPMN with an associated invasive carcinoma
MCN with an associated invasive carcinoma
Solid-pseudopapillary neoplasm
 Pancreatic Cysts

Tanaka et al. Pancreatology 2012 (International Consensus Guidelines)

 Solid Pseudopapillary
Neoplasms
N = 62
9 (15%) malignant
No factors that predicted malignancy
N = 106 who underwent surgery
17 high-grade dysplasia
>5 cm was associated with an
increased risk of high-grade
dysplasia
Lee et al. Arch Surg 2008
Kim et al. Br J Surg 2014
 Pancreatic Cystic Lesions
To be, or not to be, that is the
question
- William Shakespeares play Hamlet

To operate or to observe, that is the

question.
-Gastroenterologists and surgeons
managing pancreatic cysts
 Are these results
acceptable?
N=74
Preoperative classification as
mucinous or nonmucinous was
correct in 74%
Path with higher malignancy potential
than the preop diagnosis in 7%
Benign path with preop diagnosis of
premalignant or malignant in 20%

Cho et al. Ann Surg Oncol 2009

 Goals in Managing PCNs
Desirable outcomes
Benign PCN - observation
Malignant PCN - resection
Premalignant PCN - resection before
malignant transformation occurs
Undesirable outcomes
Benign PCN undergoing resection
Malignant PCN being observed
Premalignant PCN - resection after malignant
transformation occurs
Pancreatic Cystic Lesions
Cysts to Resect Cysts to Observe
Cystadenocarcinoma
Malignant IPMN Pseudocyst
Main duct IPMN Serous cystadenoma
Branch duct-IPMN (BD- (SCN)
IPMN) with high risk BD-IPMN without
features worrisome features or
Solid pseudopapillary high risk features
neoplasm Small cystic
Cystic neuroendocrine neuroendocrine tumor
tumor >2 cm
Pancreatic Cystic Lesions
Easy to diagnose w/o
EUS FNA Difficult
Macrocystic
to diagnoseSCN vs.FNA
w/o EUS
Pseudocyst with history MCN
of pancreatitis Macro and Microcystic
Typical serous SCN vs. BD IPMN
cystadenoma Pseudocyst without
Typical mucinous history of pancreatitis
cystadenoma vs. MCN
Typical IPMN Cystic neuroendocrine
Cystadenocarcinoma tumor
Solid pseudopapillary Mural nodule/mucus
neoplasm plug in PD or PD side
branch
Diagnostic Tools and Their Limitations
CT and MRI
CLPs have heterogeneous appearance on imaging and share many morphological
features
EUS
Technical expertise may not be available
Accuracy no greater than 80%
EUS FNA
Usually paucity of cells
Nondiagnostic
Cytobrushing significantly more likely to detect intracellular mucin than FNA (62%
vs. 23%)
Cystic fluid
Cytology
Amylase
Viscosity
CEA
Needle based confocal laser endomicroscopy (nCLE)
 Serous Cystadenoma

CT, PV phase 3D T1 FS post Gad 2D T1 Out-of-Phase

T2 fat sat Diffusion ADC MapEric Tamm

Mucinous Cystadenoma

T1 Delayed Post T2, Fat Sat

Gadolinium, Fat Sat Capsule T2 hypointense
Eric Tamm
14
 Mucinous
Cystadenocarcinoma

d d

T1 Delayed Post T2, Fat Sat, Eric Tamm

Gadolinium, Fat Sat, enh capsule Capsule T2 hypointense
Mixed Main Duct and Side Branch
IPMN

3D MIP MRCP 3D MRCP Single Image

Eric Tamm
17
Pseudopapillary Tumor

Eric Tamm
Cystic Islet Cell tumor

Eric Tamm
Cooperative Pancreatic Cyst Study
N=341
112 surgical resection; 68 mucinous, 7 serous, 27
inflammatory, 5 endocrine, and 5 others

Brugge et al. Gastroenterol 2004

Cooperative Pancreatic Cyst Study

Brugge et al. Gastroenterol 2004

Cooperative Pancreatic Cyst Study

Brugge et al. Gastroenterol 2004

 nCLE

Konda et al. Endoscopy 2013

Nakai et al. Gastrointest Endosc 2015
Napoleon et al. Endoscopy 2014
 Diagnostic Tools and Their
Limitations
CT and MRI
CLPs have heterogeneous appearance on imaging and share many
Therefore, guidelines would be extremely
EUS
morphological features

useful in the initial management of CLPs if

Technical expertise may not be available
Accuracy no greater than 80%

they can be applied to CLPs detected on

EUS FNA
Usually paucity of cells
Nondiagnostic
cross-sectional imaging
Cytobrushing significantly more likely to detect intracellular mucin than FNA
(62% vs. 23%)
Cystic fluid
Cytology
Amylase
Viscosity
CEA
nCLE
 Guidelines
ASGE guidelines 2005
International Consensus Guidelines
2006 (Sendai)
ACG guidelines 2007
International Consensus Guidelines
2012 (Fukuoka)
AGA guidelines 2015
Tanaka et al. Pancreatology 2006 (Sendai Guidelines)
Tanaka et al. Pancreatology 2012
Lennon and Wolfgang. J Gastrointest Surg 2013
Vege et al.
Gastroenterol
2015 (AGA)
Lennon and Wolfgang. J Gastrointest Surg 2013
 Sendai Consensus
Guidelines
Risk stratification for IPMN and MCN
Resect all main PD IPMN, mixed-type
IPMN and MCN
Resect BD-IPMN with high risk features
Intracystic mural nodule
Main PD dilation > 10 mm
>3 cm
Observe BD-IPMN without high risk
features
Tanaka et al. Pancreatology 2006
 Fukuoka Consensus
Guidelines
Risk stratification for IPMN and MCN
Resect BD-IPMN with high risk features
Main PD dilation > 10 mm
Jaundice resulting from PCN in the head
Enhancing solid nodule within the cyst
Worrisome features not necessarily requiring
immediate resection
Main-duct IPMN with PD 5-9 mm
Symptomatic pancreatitis
>3 cm
Thickened/enhancing cyst walls
Nonenhancing mural nodule
Abrupt change in caliber of the PD

Tanaka et al. Pancreatology 2012

A Population-Based Cohort Study on
PCN
N = 1735 with PCN, retrospective
Median follow-up 23.4 months
Incidence of malignancy: 0.4 % / year with a
standardized incidence ratio of 35
Increased risk for malignancy
Larger size
>3 cm, 9.3 % risk
1-3 cm with main PD dilation, 13.6 % risk
Main PD dilation
Absence sepatations with calcification
Growth of the cyst during follow-up
Wu et al. Am J Gastroenterol 2014
 How did we fare with Sendai
Consensus Guidelines?
N=105
<3 cm; rate of malignancy 34%
N=123 BD-IPMN
69 Sendai negative; 17 (25%) with HGD
or invasive ductal carcinoma
Limitations
No details on worrisome features,
changes in size
Prescreening with EUS; selection bias
Wong et al. J Gastrointest Surg 2013
Fritz et al. Ann Surg 2012
 How did we fare with Fukuoka
Consensus Guidelines?
N=563, 240 resection
<3 cm BD-IPMNs; 6.5 % with HGD
>3cm; 8.8% with HGD including one
invasive carcinoma

Sahora et al. Ann Surg 2013

Comparison of the Utility of Sendai and
Fukuoka guidelines in Clinical Setting
N=317 surgical resection of PCLs (47
EUS)
56% were potentially malignant/malignant
Fukuoka guidelines vs. Sendai guidelines
for pre-malignant/malignant lesions
PPV: 88 vs. 67 %
NPV: 92.5 vs. 88 %
Retrospective study
IPMNs comprised only 21 % of all PCLs

Goh et al. Ann Surg Oncol 2014

 EUS guided Therapy
Authors Year # of Agents # of Follow- # with Remarks
patien used patient up resoluti
ts s in on of
follow- cyst
up
Gan et al. 200 25 Ethanol 23 6 12 8 (35%) Non-
5 m significant
trend,
>50%
Oh et al. 200 14 Ethanol 14 9m 11 1 mild
8 + (media (79%) pancreatit
Paclitaxe n) is
l
Oh et al. 201 52 Ethanol 47 21.7 m 29 1 mid
1 lavage (media (62%) pancreatit
followed n) CR is
by 6 (13%) & Splenic
Gan et al. Gastrointest Endosc 2005 Paclitaxe PR vein
Oh et al. Gastrointest Endosc 2008
Oh et al Gastroenterology 2011
l 12 obliteratio
(36%) n
 Acknowledgements
Eric Tamm, MD; Radiology
Dan Davis, DO; Pathology