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Pancreas Cysts: An Incidental Pancreas Cysts: An Incidental Finding or Harbinger of MalignancyFinding or Harbinger of Malignancy

William R. William R. BruggeBrugge, MD, FACG, MD, FACG

Professor of MedicineProfessor of Medicine

Harvard Medical SchoolHarvard Medical School

Director, GI Director, GI EndoscopyEndoscopy UnitUnit

Massachusetts General HospitalMassachusetts General Hospital

Cysts: Early Cysts: Early NeoplasiaNeoplasia

MalignantSerous

Cyst with associated mass

Macrocystic

Microcystic

Morphology

Mucinous

Pseudocyst / InflammatoryCavity

Mucinous Cystic LesionsMucinous Cystic Lesions

Cystic lesions of the pancreas. A diagnostic and management dilemma.Pancreatology. 2008;8(3):236-51. Garcea G, Pollard CA, Berry DP, Dennison AR.

EUSEUS--guided guided FNAFNA

Linear e-scope

Color Doppler

Aspiration needle

Transgastric or transduodenal aspiration

Cytologyendoscopy

EUScytology

Mucinous Cystic Mucinous Cystic NeoplasmNeoplasm

Macrocystic lesionsMacrocystic lesions Viscous (1.8), mucoid fluidViscous (1.8), mucoid fluid Fluid analysis: CEA>200, low Fluid analysis: CEA>200, low

amylase, DNA >40ng/mlamylase, DNA >40ng/ml MucinMucin--secreting epithelial secreting epithelial

cellscells Malignant potentialMalignant potential

cytology

Histology

Cyst fluid

CEA

Types of IPMNTypes of IPMN

Side branch

Main Duct

Gross

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Tissue Types of IPMNTissue Types of IPMN

Gastric Villous-intestinal Pancreatic-Biliary MalignantSurgery. 2010 Jan 7. Invasie carcinoma derived from the nonintestinal type intraductal papillary mucinous neoplasm of the pancreas has a poorer prognosis than that derived from the intestinal type.Sadakari Y, Ohuchida K, Nakata K, Ohtsuka T, Aishima S, Takahata S, Nakamura M, Mizumoto K, Tanaka M.

Low grade dysplasia

(adenoma)

Low grade dysplasia

(adenoma)

Moderate dysplasia

(Borderline)

Moderate dysplasia

(Borderline)

CarcinomaCarcinoma

Grading of IPMNGrading of IPMN

Chromoendoscopy of IPMNChromoendoscopy of IPMN

Brian C. Brauer MD, Norio Fukami MD and Yang K. Chen MDDirect cholangioscopy with narrow-band imaging, chromoendoscopy, and argon plasma coagulation of intraductal papillary mucinousneoplasm of the bile duct (with videos) Gastrointest Endosc. 2008 Mar;67(3):574-6.

Narrow Band Imaging

Chromoendoscopy

Types of IPMN by CT scanningTypes of IPMN by CT scanning

World J Gastroenterol. 2009 Aug 28;15(32):4037-43.Imaging features of intraductal papillary mucinous neoplasms of the pancreas in multi-detector row computed tomography.Tan L, Zhao YE, Wang DB, Wang QB, Hu J, Chen KM, Deng XX.

Benign Side-Branch Malignant main duct

MRCP of IPMNMRCP of IPMN

Waters JA, Schmidt CM, Pinchot JW, Akisik F, Howard TJ, Nakeeb A, Zyromski NJ, Lillemoe KD.CT vs MRCP: optimal classification of IPMN type and extent.J Gastrointest Surg. 2008 Jan;12(1):101-9.

Benign side branch Malignant main duct

EUS of IPMN Adenoma: type IIEUS of IPMN Adenoma: type II

Ann Surg. 2009 Apr;249(4):628-34.Intraductal papillary mucinous neoplasms of the pancreas: differentiation of malignant and benign tumors by endoscopic ultrasound findings of mural nodules. Ohno E, Hirooka Y, Itoh A, Ishigami M, Katano Y, Ohmiya N, Niwa Y, Goto H.

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EUS: NonEUS: Non--invasive malignancy: invasive malignancy: type IIItype III

EUS: Malignant Nodule: type IVEUS: Malignant Nodule: type IV

EUS of IPMN: nodulesEUS of IPMN: nodules

Ann Surg. 2009 Apr;249(4):628-34.Intraductal papillary mucinous neoplasms of the pancreas: differentiation of malignant and benign tumors by endoscopic ultrasound findings of mural nodules.Ohno E, Hirooka Y, Itoh A, Ishigami M, Katano Y, Ohmiya N, Niwa Y, Goto H.

Presence of Nodules in Resected Specimens as a Function of Histologic Subtype of Br-IPMN

0

8.5

43.8

75

0

10

20

30

40

50

60

70

80

90

100

Adenoma (0/66) Boderline (4/47) Carcinoma in situ (7/16) Invasive Carcinoma(12/16)

Histologic Subtype

% S

pec

imen

s w

ith

No

du

les

BD-IPMN: histology vs. nodules

Gastroenterology. 2007 Jul;133(1):72-9; Branch-duct intraductal papillary mucinous neoplasms: observations in 145 patients who underwent resection.Rodriguez JR, Salvia R, Crippa S, Warshaw AL, Bassi C, Falconi M, Thayer SP, Lauwers GY, Pederzoli P, Fernández-Del Castillo C.

Using Nodules and Size to Predict Malignancy

Ann Surg Oncol. 2008 Jan;15(1):199-205. Treatment guidelines for branch duct type intraductal papillary mucinous neoplasms of the pancreas: when can we operate or observe?Jang JY, Kim SW, Lee SE, Yang SH, Lee KU, Lee YJ, Kim SC, Cho BH, Yu HC, Yoon DS, Lee WJ, Lee HE, Kang GH, Lee JM.

Survival: IPMNSurvival: IPMN

Thomas Schnelldorfer, MD; Michael G. Sarr, MD;;; Michael B. Farnell, MD Experience With 208 Resections for Intraductal Papillary Mucinous Neoplasm of the PancreasArch Surg. 2008 Jul;143(7):639-46;

4

MR or thin slice CT yearly No

MR or CT

1-2 cm every 6-12 mo

2-3 cm every 3-6 moStable lesion without nodules

Symptomatic, size >3 cm or

Positive high-risk stigmata

YesEUS: Mural nodulesDilated Main DuctMalignant cytology

Resect

Size <1cm Size 1-3cm Size >3cm

Monitoring of Side Branch IPMN LesionsMonitoring of Side Branch IPMN Lesions

International consensus guidelines for management of intraductal papillary mucinous neoplasms and mucinous cystic neoplasms of the pancreas.Pancreatology. 2006;6(1-2):17-32.

Markov modeling: Management of Markov modeling: Management of pancreatic cystic lesionspancreatic cystic lesions

Gastroenterology. 2010 Feb;138(2):531-40. Asymptomatic pancreatic cystic neoplasms: maximizing survival and quality of life using Markov-based clinical nomograms.Weinberg BM, Spiegel BM, Tomlinson JS, Farrell JJ.

At 65 years old At 65 years old ……2cm cyst2cm cyst

Survival QoL

But if at 65 years old But if at 65 years old …… 3cm cyst3cm cyst

Survival QoL

Findings of the Markov ModelFindings of the Markov Model

For patients focused on overall survival, regardless of quality of life, surgery is optimal for lesions >2cm.

For patients focused on quality-adjusted survival, a 3cm threshold is more appropriate for surgery except for the extreme elderly.

Gastroenterology. 2010 Feb;138(2):531-40. Asymptomatic pancreatic cystic neoplasms: maximizing survival and quality of life using Markov-based clinical nomograms.Weinberg BM, Spiegel BM, Tomlinson JS, Farrell JJ.

Indications for Surgical Indications for Surgical ResectionResection

Recurrent pancreatitis

Main duct disease

Cystic lesion >3cm

Rising CA 19-9

Malignant cytology

J Clin Gastroenterol. 2010 May 5. Predictors of Malignant Intraductal Papillary Mucinous Neoplasm of the Pancreas.Mimura T, Masuda A, Matsumoto I, Shiomi H, Yoshida S, Sugimoto, Kutsumi H, Ku Y, Azuma T.

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Ethanol AblationEthanol AblationEPIC TrialEPIC Trial

Prospective, randomized trial of ethanol vs saline lavage

1-3cm cystic lesion

4 patients underwent resection (histology) 42 pts

25 pts lavagedwith ethanol

12/25 resolved

17 pts lavaged with saline

0/17 resolved

ethanolsaline

EUS-guided ethanol versus saline solution lavage for pancreatic cysts: a randomized, double-blind study.DeWitt J, McGreevy K, Schmidt CM, Brugge WR.Gastrointest Endosc. 2009 Oct;70(4):710-23. Epub 2009 Jul 4.

ConclusionsConclusions

IPMN is a common malignancy Main

Side Branch

Slowly progressive

Resect: main duct disease, high risk lesions, size>3cm with nodule