KOK SIU YAN AMY

United Christian Hospital

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Introduction Classification Investigation Indication for resection Methods of resection Follow-up Prognosis

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History: 1982Described by Ohashi and his colleagues

Incidence ~2.04 per 100 000 Autopsy studies 25% of cystic

pancreatic lesions 30-50% may become invasive Accounts for 5-7% of all pancreatic

neoplasm

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Dtsch Arztebl Int. 2011 Nov;108(46):788-94.Intraductal papillary mucinous neoplasia (IPMN) of the pancreas: its diagnosis, treatment, and prognosis.Grützmann R, Post S, Saeger HD, Niedergethmann

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Dtsch Arztebl Int. 2011 Nov;108(46):788-94..Intraductal papillary mucinous neoplasia (IPMN) of the pancreas: its diagnosis, treatment, and prognosis.Grützmann R, Post S, Saeger HD, Niedergethmann M.

First international consensus guideline in 2006 and was revised in 2012

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Main duct Branch duct Mixed

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USG CT MRI + MRCP EUS +/- FNAC ERCP Intraductal USG or pancreatoscopy

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USGSize and extent

CTDiffusely distended pancreatic duct with

mucinous filling defects and cystic space occupying lesions

Sensitivity 42%

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MRI with MRCPEntire pancreatic parenchyma and the intra-

abdominal organsMore sensitive to detect mural nodulesSensitivity 88%

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Br J Surg. 2009 Jan;96(1):5-20.Preoperative tissue diagnosis for tumours of the pancreas.Hartwig W, Schneider L, Diener MK, Bergmann F, Büchler MW, Werner J.

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EUS-FNACEAAmylaseCytologyMolecular analysis

Investigational Small BD-IPMN

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MD-IPMN BD-IPMN

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Main duct dilatation≥1cm Frequency of malignancy: 60-92% No clinical parameters accurately

discriminate malignant and non-malignant lesion

RESECT ALL MAIN DUCT AND MIXED VARIANT IPMN

IF SURGICALLY FIT

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High-risk stigmata Obstructive jaundice in patient with cystic

lesion of the head of pancreasEnhancing solid component within cystMain pancreatic duct ≥10mm in size

CONSIDER SURGERY IF CLINICALLY APPROPRIATE

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Worrisome featuresClinical: pancreatitis Imaging:

cyst≥3cm Thickened/enhancing cyst walls Main duct size 5-9mm Non-enhancing mural nodule Abrupt change in calibre of pancreatic duct with

distal pancreatic atrophy

PERFORM ENDOSCOPIC ULTRASOUND

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EUS features:Definite mural noduleMain duct features suspicious for

involvementCytology: suspicious or positive for

malignancy

CONSIDER SURGERY IF CLINICALLY APPROPRIATE

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MD-IPMNMain duct dilatation≥5mm5-9mm worrisom features

Evaluation No immediate resection

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According to site and extend of diseasePancreatoduodenectomyDistal pancreatectomyTotal pancreatectomy

Limited resection ExcisionEnucleationUncinatectomy

Laparoscopy

+/- lymph node dissection

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Non-resected IPMN Surgically resected IPMN

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Benign:Yearly CT/MRI

Malignant6 monthly CT/MRICEA & CA19.9 no value

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Surgical margin statusnormal pancreatic tissuenon-dysplastic changes low grade dysplasiamoderate grade dysplasia invasive carcinoma

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Repeat exam 2-5 years

Hx/PE/MRCP half-yearly

Identical to PDAC

Complete resection of noninvasive IPMN5 year survival rate 95%

Complete resection of early stage tumors(T1N0)5 year survival rate 60%

Advanced or nodal positive tumors5 year survival rate 36%

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High-risk stigmata surgery Smaller cyst + worrisome features

EUS Cyst >3cm + NO worrisome features

EUS if elderly Cyst ≤3cm + NO worrisome features

surveillance

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High incidence of malignant/invasive lesions (61.6%/43.1%)

Segmental ectatic type/Diffuse type with focal lesions

Diffuse type without focal lesions Frozen section Intraductal USG/pancreatoscopy

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Mean frequency of malignancy/invasive cancer (25.5/17.7%)

Elderly Annual malignancy risk 2-3%

High risk factors:Mural nodulesHigh grade dysplasia/Positive cytology Rapidly increasing size

Individual decision

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One 1st degree relative with PDAC 2.3-fold increased risk

high-quality MRI/MRCP or CT and EUSMalignant stigmata/worrisome features

resectionNo malignant stigmata/worrisome features

MRI/MRCP or CT at 3-month intervals EUS annually for first 2 years

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Combination of clinical & imaging characteristics can provide preoperative diagnosis of cyst type

Multidetector CT (MDCT) & MRCP are useful for defining morphology, location, multiplicity, and communication with the MPD

Distinguishing features: multiplicity & visualisation of a connection to MPD

EUS: delineate malignant characteristics eg mural nodules & invasion but operator dependent

Cyst fluid x CEA, amylase & cytology cannot distinguish MCN & IPMN

Molecular analysis for GNAS mutations can distinguish MCN from BD-IPMN

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3 morphological patterns:Polycystic Honeycomb Oligocystic

Distinguished from SCN with a polycystic or honeycomb pattern by CT or MRCP

Differentiation between a small oligocystic SCN & a BD-IPMN may require EUS-FNA with cyst fluid CEA determination

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Neoplastic cysts:Non-mucinous

Serous cystic neoplasm (SCN) Solid pseudopapillary neoplasm (SPN)

Mucinous Mucinous cystic neoplasm (MCN) Intraductal papillary mucinous neoplasm

(IPMN)

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Low prevalence of invasive carcinoma (<15%)

Resection is recommendedYoung Risk of progression Locations in body and tail High cost of long-term FU

Distal pancreatectomy Parenchymal-sparing resection (middle

pancreatectomy) Laparoscopic

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Apart from imaging, elevated cyst fluid CEA is a marker that distinguishes mucinous from non mucinous cysts, but NOT benign from malignant cysts

A cut off of >/=192-200ng/ml is ~80% accurate for diagnosis of mucinous cyst

Cyst fluid amylase is shown to be not uniformly elevated in IPMN

Fluid cytology may add value especially for evaluation of a small BD-IPMN without “worrisome features”.

High grade epithelial atypia recognised in cyst fluid predicted malignancy in a mucinous cyst with 72% sensitivity in one study and detected 30% more cancers in small IPMN without worrisome features in another study

Some studies showed molecular analysis of cyst fluid may be helpful in distinguishing significant mucinous cysts from indolent cysts that can be conservatively managed

However, in view of the inconclusive evidence, this guideline suggests cyst fluid analysis is still investigational, but is recommended for evaluation of small BD-IPMN without worrisome features only in centres with expertise in EUS-FNA and cytological interpretation

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Synchronous/metachronous malignant diseases in extra-pancreatic organs 20-30%

Frequency and location of extra-pancreatic malignancies differsGI cancer is common in AsiaSkin/breast/prostatic cancers common in US

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This comprehensive guideline has lowered the criterion for characterising MD-IPMN to MPD dilatation of >5mm without losing specificity for radiologic diagnosis

-high risk stigmata and worrisome features have been defined to stratify risk of malignancy in BD-IPMN and consider resection or increased freq of surveillance

-resection is recommended for all surgically fit patients with MD-IPMN or MCN

Indications for resection of BD-IPMN are more conservative

BD IPMN >3cm without high risk stigmata can be observed without immediate resection

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A previous history of diabetes, especially with insulin use, CP, and family history of PDAC are all relevant risk factors for the development of IPMN. 

Am J Gastroenterol. 2013 Jun;108(6):1003-9. doi: 10.1038/ajg.2013.42. Epub 2013 Mar 5.

Risk factors for intraductal papillary mucinous neoplasm (IPMN) of the pancreas: a multicentre case-control study.

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Good past health No history of pancreatitis No family history of pancreatic cancer Physical examination: unremarkable

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Differential diagnosis

Benign– Pseudocyst– Serous cystic neoplasm (SCN)– Simple cyst, retention cyst, congential, lymphoepithelial

cyst

Potentially malignant– Intraductal papillary mucinous neoplasm (IPMN)– Mucinous cystic neoplasm (MCN)– Solid pseudopapillary neoplasm (SPN)– Neuroendocrine tumor

Malignant– Ductal adenocarcinoma

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Pathological diagnosis (n = 212)

Fernandez-del Castillo et al. Arch Surg 2003

Intraductal papillary mucinous neoplasm (IPMN)

75 (35%)

Mucinous cystic neoplasm (MCN)

43 (19%)

Serous cystadenoma 23 (11%)

Pseudocyst 29 (14%)

Ductal adenocarcinoma 14 (7%)

Others 28 (13%)

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WHO classification of digestive system 2010 IPMN with low or

intermediate grade dysplasia

IPMN with high grade dysplasia

IPMN with invasive cancer

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Criterion for characterising MD-IPMN >5mm

MD-IPMN: resection BD-IPMN:

high-risk stigmata & worrisome featuresConservative

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EUS-guided mucosal ablation by ethanol injection

Indication:Cyst >2cmUnilocular/oligolocularNo communication with MPDRefuse surgeryHigh risk surgical candidates

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CT-defined cyst resolution rates 33-79% Variable histopathologic degrees of

epithelial ablation

Complication:Acute pancreatitis (4.5-10%)Abdominal pain (<20%)Splenic vein obliteration

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ERCP Washing or brushing for cytology Not recommended

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