What To Do With Pancreatic Cysts?Pancreatic Cysts?d2j7fjepcxuj0a.cloudfront.net/wp-content/uploads/2015/01/15ACG...• Not predictive of cyst size progression1 • Serial followSerial

Kenneth J. Chang, MD, FACG

What To Do With Pancreatic Cysts?Pancreatic Cysts?


Pancreatic Cysts

• Incidence: A growing problem

•Previous diagnostic approaches

•Emerging data: the conundrum

•New problems need new psolutions

ACG Western Regional Postgraduate Course - Las Vegas, NV Copyright 2015 American College of Gastroenterology

1


Case scenario•• 65 65 yoyo female was found to have an female was found to have an

incidental 2.9 cm cyst in the head of the incidental 2.9 cm cyst in the head of the pancreaspancreas

Q 1: What would you do next?

1.1. Whipple resectionWhipple resectionpppp

2.2. Repeat CT in 12 monthsRepeat CT in 12 months

3.3. MRI/MRCPMRI/MRCP

4.4. ERCPERCP

5.5. EUS/FNAEUS/FNA


2


Very common problem•• 300 300 consecutive autopsy casesconsecutive autopsy cases11

••186 cysts (at least 0.4 cm) in 73 cases (24.3%)186 cysts (at least 0.4 cm) in 73 cases (24.3%)186 cysts (at least 0.4 cm) in 73 cases (24.3%)186 cysts (at least 0.4 cm) in 73 cases (24.3%)

••Review of 24,039 CTs/MRIsReview of 24,039 CTs/MRIs22

•• 290 290 ptspts (1.2%) had pancreatic cysts(1.2%) had pancreatic cysts•• 168 (0.7%) w/o documentation of 168 (0.7%) w/o documentation of pancreatitispancreatitis

••Review ofReview of 2 832 MDCT2 832 MDCT33••Review of Review of 2,832 MDCT2,832 MDCT33

•• 73 73 ptspts (2.6%) had pancreatic cysts(2.6%) had pancreatic cysts•• 8.7% among elderly (age 808.7% among elderly (age 80--89)89)

1 Kimura W, et al. Int J Pancreatol 1995;18:197-206.2 Spinelli KS, et al. Ann of Surg 2004; 239: 651-6593 Laffan TA, et al. AJR 2008; 191: 802-807

Pathology ClassificationNonNon--MucinousMucinous

•• Serous NeoplasmsSerous Neoplasms~~ SerousSerous cystadenomacystadenoma

Mucinous• Mucinous cystic neoplasms

– LGD (adenoma)Serous Serous cystadenomacystadenoma•• MicrocysticMicrocystic•• MacrocysticMacrocystic•• SolidSolid•• VonVon--HippelHippel--

LandauLandau~~ Serous Serous

CystadenocarcinomaCystadenocarcinoma

( )– Moderate dysplasia (borderline)– HGD (carcinoma in situ)– Invasive carcinoma

• IPMNs– LGD (adenoma)– Moderate dysplasia (borderline)

Kloppel G SE, et al. World Health Organization classification of tumors of the digestive system. Lyon: IARC Press; 2000.

Hruban RH, et al. Tumors of the pancreas. AFIP Atlas of Tumor Pathology, 4th Series, Fascicle 6. Washington, DC: Armed Forces Institute of Pathology; 2007.

y p ( )– HGD (carcinoma in situ)– Invasive carcinoma


3


Clinical Characteristics

Demographics Pseudo SCA MCN IPMN SPPT G dGender

(male:female) 1:1 1:3-4 1:9 2:1 1:10

Age (y), range 40-70 60-80 30-50 60-80 20-40

History Pancreatitis - - - -

Body/tail Body/tail HeadLocation Even Body/tail>Head

Body/tail>>Head

Head>Body/tail

Even

Katz 2008 J Am Coll Surg

Serous Cystadenoma/ Microcystic Adenoma


4


Serous Cystadenoma / Oligocystic

Mucinous Cystic Neoplasm (MCN)


5


MCN

Intraductal Papillary Mucinous Neoplasia (IPMN)


6


IPMN – Main Duct Type

IPMN – Endoscopic View


7


Tanaka et al. Pancreatology 2006

Solid Solid PseudopapillaryPseudopapillary Tumors (SPPT)Tumors (SPPT)

•• Rare neoplasms with Rare neoplasms with malignant potentialmalignant potential

•• Start as solid tumors, Start as solid tumors, undergo degeneration giving undergo degeneration giving rise to a cystic appearancerise to a cystic appearance

•• Growth rate can be dramatic Growth rate can be dramatic (>10cm)(>10cm)

•• Can arise from any part of the Can arise from any part of the pancreaspancreas

•• Predominantly young Predominantly young femalesfemales


8


Solid Pseudopapillary Tumors (SPPT)•• Imaging: Imaging:

~~Range from solid to cystic, typically bothRange from solid to cystic, typically both~~WellWell marginatedmarginated~~Well Well marginatedmarginated~~Central calcificationCentral calcification~~Well vascularized with areas of hemorrhageWell vascularized with areas of hemorrhage

Solid Pseudopapillary Tumors (SPPT)•• EUSEUS--FNA:FNA:

~~Branching papillae with Branching papillae with myxoidmyxoid stromastroma~~The diagnostic accuracy of EUSThe diagnostic accuracy of EUS--FNA 75%FNA 75%**

•• Management: Management: ~~Considered low grade malignancyConsidered low grade malignancy~~Surgical resection to prevent local tumor Surgical resection to prevent local tumor

growth and distant metastases, to palliate growth and distant metastases, to palliate ttsymptomssymptoms

~~Favorable survival even in the face of Favorable survival even in the face of advanced disease (LN advanced disease (LN metsmets are rare)are rare)

*Dewitt et al. Endoscopy 2008 Mar;40(3):200-3.


9


Pancreatic Cysts




•New problems need new psolutions

Sendai Consensus Guidelines 2004

1. Size 2. High risk features-Mural nodules-Dilated main PD (>10mm)-Positive cytology

Curr Gastroenterol Rep (2010)12:98-105


10


MCN mural nodules

Updated “Sendai” Guidelines 2012

Pancreatology 2012


11


EUS-FNA and Cyst Fluid Analysis of Cystic Pancreatic Lesions

LesionFluid Color

Viscosity CEA Amylase

PseudocystYellow/ brown

Thin Low High

SCN Colorless ThinLow/

UndetectedVariable

MCN ColorlessUsually

++ VariableMCN Colorlessy

thick++ Variable

MCAC Colorless Thick +++ Variable

IPMN ColorlessUsually

thick+ to +++ High

EUS-FNA of Pancreatic Cyst•• Cyst fluid CEA 192 Cyst fluid CEA 192 ngng/mL optimizes non/mL optimizes non--

MCN vs. MCNMCN vs. MCN11MCN vs. MCNMCN vs. MCN•• Cyst fluid cytology is insensitive but very Cyst fluid cytology is insensitive but very

specific for diagnosis, malignancy and specific for diagnosis, malignancy and MCN vs. nonMCN vs. non--MCNMCN22

•• Cyst fluid DNA may help differentiate Cyst fluid DNA may help differentiate li t/b i d ili t/b i d imalignant/benign and mucinous vs. nonmalignant/benign and mucinous vs. non--

mucinous cystsmucinous cysts33

1. Brugge WR. Gastroenterology 2004;126:1330-62. DeWitt J. Tech GI Endosc 2005;7:181-73. Khalid A, et al. GIE 2009;69:1095-1102


12


National Coop. Panc Cyst Study

80

30

40

50

60

70

MorphologyCytologyMarker Analysis

0

10

20

% Accuracy

Brugge et al, Gastroenterology, 2004

Back to Clinical Scenario

6 months later a repeat EUS shows6 months later a repeat EUS shows6 months later, a repeat EUS shows 6 months later, a repeat EUS shows no change in size or morphology, but no change in size or morphology, but the CEA level went from 168 to 550the CEA level went from 168 to 550


13


Q 2: Now what?

1. Whipple resection

2. Repeat CT in 12 months

3. MRI/MRCP in 3 months

4. ERCP

S/ 65. Repeat EUS/FNA in 6 months

Pancreatic Cysts




•New problems need new solutionsp


14


CEA•Although may help distinguish mucinous

vs non-mucinous, does not distinguish gIPMN vs MCN.

•Not predictive of malignant progression1

•Not predictive of cyst size progression1

• Serial follow-up levels may be erattic2Serial follow up levels may be erattic

1. Othman MO. Dig Liver Dis 2012; 44:844-82. Nakai Y. ASGE abstract submission 2012

Serial CEA values in 87 patients

Nakai Y. Chang K. DDW 2012

14 pts with ≥ 3 FNA’s


15


Cyst Size

•Not all small side-branch IPMN are benign, despite negative cytologydespite negative cytology

•Among 20 patients with < 3cm SB-IPMN, 6 (30%) had CIS (3) or invasive cancer (3) 1

• Cyst size > 3cm (Sendai Guideline) NOT a predictor of malignancy among 112

i l 2surgical cases2

1. Pitman MB. Pancreatology 2008:8;277-852. Genevay M. Ann Surg 2011;254:977–983

Morphology of Pancreatic Cysts by Surgical Diagnosis

Unilocular Microcystic MacrocysticCyst w/ solid componentcomponent

Pseudocyst SCA MCN MCN

Retention cyst IPMN IPMN IPMN

IPMN SCA SPT

MCNAcinar

CystadenomaPET

Pittman M. Cancer Cytopathology 2010; 118:1-13

Cystadenoma

SCA Lymphangioma Adenocarcinoma

Lymphoepithelial Metastasis

Acinar cell


16


Pancreatic Cysts: Conundrum

CEA?

Imaging?

CEA?Amylase?

Cytology?

Biomarkers?SCAMCNIPMNSPPT

Size?

The answer is on the wall…

SCA

MCN

PAS+ cuboidal glycogen-staining cells

Frossard AJG 2003

MCN


17


The answer is on the wall…

IPMN

Cytology

• Yield of cytology is lowU ll di i i h MCN IPMN•Usually cannot distinguish MCN vs IPMN

•May not distinguish grade of dysplasia, which also may require histology

• Cannot distinguish IPMN histologic subtype1,2

1. Furakawa T. Gut 2011; 60:509-162. Mino-Kenudson M. Gut 2011; 60:1712-1720


18


Why low yield of cytology?• Cells don’t ready shed in cyst fluid; diluted

• Even for brush or biopsy – neoplastic epithelium can be heterogeneous (spotty); similar to Barrett’s

Back to Clinical Scenario

You are now fairly sure that theYou are now fairly sure that theYou are now fairly sure that the You are now fairly sure that the patient has IPMNpatient has IPMN


19


Q 3: Which is most predictive of progression to cancer?

1 Male sex1. Male sex

2. Size of cyst

3. Main Duct type vs Side branch type

4. IPMN histologic subtypeg yp

5. CEA level

IPMN - 4 Histologic Types

Yamaguchi, H. Modern Pathology 2007;20, 552–561


20


IPMN - 4 Histologic Types

Gastric

OncocyticOncocytic

Intestinal

Pancreatico-biliary

Furukawa Gut 2011

283 pts with IPMN

IPMN – disease specific death

Furukawa Gut 2011


21


Pancreatic CystsPancreatic Cysts




•New problems need new solutions

EUS-nCLE(needle confocal laser endomicroscopy)

nCLE

19 G FNA

Mauna Kea Technologies AQ-Flex 19


22


Pancreatic Cysts: nCLEATRAUMATICATRAUMATIC DIFFUSE SAMPLINGDIFFUSE SAMPLING

Pancreatic Cysts: nCLE


23


nCLE - IPMN

nCLE - IPMN


24


EUS nCLE IPMN

AGA #1204 An International, MultiAn International, Multi--Center Trial Center Trial on Needleon Needle--Based Confocal Laser Based Confocal Laser

EndomicroscopyEndomicroscopy ((nCLEnCLE): Results From the In ): Results From the In Vivo CLE Study in the Pancreas With Vivo CLE Study in the Pancreas With

EndosonographyEndosonography of Cystic Tumors of Cystic Tumors (INSPECT)(INSPECT)g p yg p y yy ( )( )VaniVani J. J. KondaKonda, , Alexander Alexander MeiningMeining, , LaithLaith H. H. JamilJamil, , Marc Marc GiovanniniGiovannini, ,

Kenneth J. Kenneth J. Chang, Chang, JooJoo Ha Ha Hwang, Hwang, Michael B. Michael B. Wallace, Wallace, UzmaUzma D. D. SiddiquiSiddiqui, , Harry R. Harry R. AslanianAslanian, , Simon K. Simon K. Lo, Lo, Michael D. Michael D. Saunders, Saunders,

John John Hart, Hart, Irving Irving WaxmanWaxman

ASGE #500 Diagnosis of Pancreatic Cysts: Diagnosis of Pancreatic Cysts: Endoscopic Ultrasound ThroughEndoscopic Ultrasound Through--thethe--NeedleNeedleEndoscopic Ultrasound, ThroughEndoscopic Ultrasound, Through thethe Needle Needle

Confocal LaserConfocal Laser--Induced Induced EndomicroscopyEndomicroscopy and and Cystoscopy Trial Cystoscopy Trial ((DETECT)DETECT)

YousukeYousuke NakaiNakai, , TakujiTakuji Iwashita, Do Hyun Park, Jason B. Iwashita, Do Hyun Park, Jason B. SamarasenaSamarasena, John G. Lee, Kenneth J. Chang , John G. Lee, Kenneth J. Chang

DDW 2012


25


nCLE

• Presence of villous structures high specificity

for Mucinous Neoplasia

• But sensitivity only 59%

Konda VJ, et al. INSPECT study. Endoscopy. Dec 2013;45(12):1006-1013

Can we improve nCLE with “red flag” technology?

• EUS can only detect obvious noduleF B tt’ h d & NBI• For Barrett’s, we have endoscopy & NBI

• Why not do “cystoscopy” to guide nCLE?


26


EUS-guided “through the needle” Cystoscopy

SCA MCN IPMNSmooth wallClear fluid

Smooth wallCloudy fluid

Papillary projectionsCloudy fluid

Cystoscopy

SCA

IPMNMCNNakai, Chang, et al DETECT study. GIE. 2015 (in press)


27


Conclusions (1)

•• Pancreatic cysts are Pancreatic cysts are increasingly recognized increasingly recognized with routine use of crosswith routine use of cross sectional imagingsectional imagingwith routine use of crosswith routine use of cross--sectional imagingsectional imaging

•• WWide range of diagnosis: from benign to ide range of diagnosis: from benign to malignant (and everything in between)malignant (and everything in between)

•• Many have characteristic (but overMany have characteristic (but over--lapping) lapping) imagingimaging and demographicand demographic characteristicscharacteristicsimaging imaging and demographic and demographic characteristicscharacteristics

Conclusions (2)

•• Cyst fluid CEA does not appear to predict Cyst fluid CEA does not appear to predict malignant transformationmalignant transformationmalignant transformationmalignant transformation

•• Clinical decisionClinical decision--making based on cyst making based on cyst size alone is inadequatesize alone is inadequate

•• Histologic subtyping and degree of Histologic subtyping and degree of d l i i i t t f i kd l i i i t t f i k t tifi tit tifi tidysplasia is important for riskdysplasia is important for risk--stratification stratification and will require new techniques for tissue and will require new techniques for tissue sampling and/or intrasampling and/or intra--cystic imagingcystic imaging


28


What To Do With Pancreatic Cysts?Pancreatic Cysts?



29

Documents

What To Do With Pancreatic Cysts?Pancreatic Cysts?d2j7fjepcxuj0a.cloudfront.net/wp-content/uploads/2015/01/15ACG...• Not predictive of cyst size progression1 • Serial followSerial