1. 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

2. Pancreatic Cystic Lesions (PCLs)
Non-neoplastic pancreatic cysts
Pseudocyst
Congenital cyst
Retention cyst
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

3. 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

4. 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

5. Pancreatic Cysts
Tanaka et al. Pancreatology 2012 (International Consensus Guidelines)

6. Solid Pseudopapillary Neoplasms
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

7. Pancreatic Cystic Lesions
“To be, or not to be, that is the question…” - William Shakespeare’s play Hamlet “To operate or to observe, that is the question.” -Gastroenterologists and surgeons managing pancreatic cysts

8. 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

9. Goals in Managing PCNs Desirable outcomes Undesirable 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

10. Pancreatic Cystic Lesions
Cysts to Resect
Cysts to Observe
Cystadenocarcinoma
Malignant IPMN
Main duct IPMN
Branch duct-IPMN (BD-IPMN) with high risk features
Solid pseudopapillary neoplasm
Cystic neuroendocrine tumor >2 cm
Pseudocyst
Serous cystadenoma (SCN)
BD-IPMN without worrisome features or high risk features
Small cystic neuroendocrine tumor

11. Pancreatic Cystic Lesions
Easy to diagnose w/o EUS FNA
Difficult to diagnose w/o EUS FNA
Pseudocyst with history of pancreatitis
Typical serous cystadenoma
Typical mucinous cystadenoma
Typical IPMN
Cystadenocarcinoma
Solid pseudopapillary neoplasm
Macrocystic SCN vs. MCN
Macro and Microcystic SCN vs. BD – IPMN
Pseudocyst without history of pancreatitis vs. MCN
Cystic neuroendocrine tumor
Mural nodule/mucus plug in PD or PD side branch

12. 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)

13. Serous Cystadenoma CT, PV phase 3D T1 FS post Gad 2D T1 Out-of-Phase
Consider showing case of metastatic serous cystadenoma
T2 fat sat
Diffusion
ADC Map
Eric Tamm

14. Mucinous Cystadenoma T1 Delayed Post Gadolinium, Fat Sat T2, Fat Sat
Capsule T2 hypointense
Eric Tamm 14

15. Mucinous Cystadenocarcinoma
T1 Delayed Post
Gadolinium, Fat Sat, enh capsule
T2, Fat Sat,
Capsule T2 hypointense
Eric Tamm

17. Mixed Main Duct and Side Branch IPMN
3D MIP MRCP
3D MRCP Single Image
Eric Tamm

18. Pseudopapillary Tumor
Eric Tamm

19. Cystic Islet Cell tumor
Eric Tamm

20. Cooperative Pancreatic Cyst Study
112 surgical resection; 68 mucinous, 7 serous, 27 inflammatory, 5 endocrine, and 5 others
Brugge et al. Gastroenterol 2004

21. Cooperative Pancreatic Cyst Study
Brugge et al. Gastroenterol 2004

22. Cooperative Pancreatic Cyst Study
Brugge et al. Gastroenterol 2004

23. nCLE Konda et al. Endoscopy 2013 Nakai et al. Gastrointest Endosc 2015
Napoleon et al. Endoscopy 2014

24. 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
nCLE
Therefore, guidelines would be extremely useful in the initial management of CLPs if they can be applied to CLPs detected on cross-sectional imaging

25. Guidelines ASGE guidelines 2005
International Consensus Guidelines 2006 (Sendai)
ACG guidelines 2007
International Consensus Guidelines 2012 (Fukuoka)
AGA guidelines 2015

26. Tanaka et al. Pancreatology 2006 (Sendai Guidelines)

27. Tanaka et al. Pancreatology 2012
Lennon and Wolfgang. J Gastrointest Surg 2013

28. Vege et al. Gastroenterol 2015 (AGA)

29. Lennon and Wolfgang. J Gastrointest Surg 2013

30. 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

31. 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

32. 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

33. How did we fare with Sendai Consensus Guidelines?
<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

34. 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

35. 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

36. EUS – guided Therapy Authors Year # of patients Agents used
# of patients in follow-up
Follow-up
# with resolution of cyst
Remarks
Gan et al.
2005 25
Ethanol 23
6 – 12 m
8 (35%)
Non-significant trend, >50%
Oh et al.
2008 14 +
Paclitaxel
9 m (median)
11 (79%)
1 mild pancreatitis
2011 52
Ethanol lavage followed by Paclitaxel 47
21.7 m
(median)
29 (62%) CR
6 (13%) PR
12 (36%) NR
1 mid pancreatitis
& Splenic vein obliteration
Gan et al. Gastrointest Endosc 2005
Oh et al. Gastrointest Endosc 2008
Oh et al Gastroenterology 2011

37. Acknowledgements
Eric Tamm, MD; Radiology
Dan Davis, DO; Pathology