Management of IPMN

1. Intraductal papillary
mucinous neoplasm
(IPMN)
PHONGTHORN TUNTIVARARUT
POLICE GENERAL HOSPITAL
BANGKOK, THAILAND

2. Introduction
 Intraductal papillary mucinous neoplasm (IPMN) > pancreatic cyst
 Male : Female (MD-IPMN and BD-IPMN in Asia) >> 3 : 1.8
 Asymptomatic  present with abdominal discomfort
 Malignancy in MD-IPMN and mixed-type IPMN  60%
(Invasive cancer 45%)
 Malignancy in BD-IPMN  25% (Invasive cancer < 20%)
Tanaka M, et al. Pancreatology 2017;17:738-53

3. Morphologic classification
 Main duct IPMN (MD-IPMN)
 Mean frequency of Inv-IPMN and HGD = 61.6% (Inv-IPMN 43.1%)
 Branch duct IPMN (BD-IPMN)
 Mean frequency of Inv-IPMN and HGD = 31.1% (Inv-IPMN 18.5%)
 Mixed type IPMN
 Minimal MPD involvement
 Extensive MPD involvement
Tanaka M, et al. Pancreatology 2017;17:738-53

4. Morphologic Classification
Sahani DV, et al. Clin Gastroenterol Hepanol 2009;7:259-269
MD-IPMN
Mixed
type-IPMN
BD-IPMN

5. Histologic subtypes
 Gastric
 most common in BD-IPMN
 Papilla lining
 MUC5AC - positive
 MUC1 and MUC2 – negative
 If carcinoma develop  tubular
type
 Intestinal
 most common in MD-IPMN
 33% - invasive carcinoma
 Colloid type
 MUC2 and CDX2 - positive
Tanaka M, et al. Pancreatology 2017;17:745

6. Histologic subtypes
 Pancreatobiliary
 Rare
 Tubular type and aggressive
 Oncocytic
 Complex multilocular cyst
 Ductal dilatation
 Mucin extrusion (Ampulla)
 MUC6 – positive
 Good prognosis
Tanaka M, et al. Pancreatology 2017;17:745

7. Carlos Fernandez-del Castillo, et al. Gastroenterology 2010;139:708-713

8. Grading of dysplasia
 Low grade dysplasia (LGD)
 Intermediate grade dysplasia (IGD)
 High grade dysplasia (HGD)
 Invasive carcinoma (Inv-IPMN)
 pT1a  invasive carcinoma ≤ 5mm
 pT1b  invasive carcinoma 5-10 mm
 pT1c  invasive carcinoma 10-20 mm
Malignant IPMN
Tanaka M, et al. Pancreatology 2017;17:738-53

9. Investigation
Ultrasound CT scan MRCP
Ann Gastroenterol. 2018 Jab-Feb; 31(1): 90-95

10. Once detection of the Cyst..
 Pancreatic cyst < 5 mm, no symptom and no invasive carcinoma
characteristic  F/U imaging
 Pancreatic cyst > 5 mm  MRCP
 “procedure of choice” for evaluating pancreatic cyst
Tanaka M, et al. Pancreatology 2017;17:738-53

11. EUS-FNA
 For cyst fluid and tissue cytology
 Limitation: Operator dependent
 For diagnosis (HGD&Inv-IPMN)
in mucinous cyst
 Sensitivity 72%
 Positive predictive value 80%
Tanaka M, et al. Pancreatology 2017;17:738-53
SEEDING…????

12. Ngamruengphon S, et al. Endoscopy 2013;45:619-26
EUS-FNA >> not associated with a risk of needle track seeding

13. ERCP with brushing and washing
cytology
 Mural nodule size > 5 mm
 CEA level in pancreatic juice > 30 ng/ml
 Useful for diagnosis HGD and Inv-IPMN in BD-IPMN
 Positive predictive value 100%
 Negative predictive value 96.3%
Hirono S, et al. Ann Surg 2012;255:517-22

14. High risk stigmata of malignancy
Obstructive jaundice with pancreatic head cyst
Enhancing solid component within cyst (≥ 5 mm)
MPD size ≥ 10 mm
Tanaka M, et al. Pancreatology 2017;17:738-53

15. Worrisome features
 Clinical pancreatitis
 Cyst size ≥ 3 cm
 Enhancing mural nodule < 5 mm
 Thickened enhanced cyst walls
 MPD size 5-9 mm
 Abrupt change of MPD caliber with
distal pancreatic atrophy
 Lymphadenopathy
 Rising serum CA19-9
 Rapid growth rate ≥ 5mm/2years
Tanaka M, et al. Pancreatology 2017;17:738-53

16. “
”
Main duct IPMN
(MD-IPMN)

17. Main duct IPMN (MD-IPMN)
 Features suspected MD-IPMN
 Diffuse dilatation of MPD
 Thickened wall of MPD
 Intraductal mucin or mural nodule
 Incidence of Inv-IPMN and HGD in MD-
IPMN is 61.6%
 Incidence of Inv-IPMN alone ~ 43.1%)
 5 year survival rates 31-54%
Tanaka M, et al. Pancreatology 2017;17:738-53

18. Indications for resection in MD-IPMN
 Strongly recommend for all surgically fit patients with
 MPD > 10 mm
 Jaundice
 Mural nodules
 In MPD 5-9 mm (WF): no immediate resection
 There is no cut-off size of mural nodule to predict Inv-IPMN or HGD
in MD-IPMN
Tanaka M, et al. Pancreatology 2017;17:738-53

19. Resection of MD-IPMN
 Diffuse MPD dilation & no focal lesion >> ERCP
 Mucin extrusion or mural nodule  MD-IPMN
 Aim of resection >> complete removal of tumor
with negative margin
 MD-IPMN at middle segment or pancreatic body
>> right sided pancreatectomy or
pancreaticoduodenetomy
 Frozen section  for adequate margin
Tally NJ, Practical Gastroenterology&Hepatology; 2010

20. Intraoperative frozen section
 HGD or invasive carcinoma is present at the margin
 Further resection until negative margin
 LGD - not require any further therapy
 Low-grade pancreatic intraepithelial neoplasia (PanIN)
 As LGD - no further resection
 Negative margin in frozen but Inv-IPMN at margin ***
 Closed follow-up
Tanaka M, et al. Pancreatology 2017;17:738-53

21. Total pancreatectomy in MD-IPMN
 Consider in patient
 Definitive diagnosis
 Size of MPD dilation
 Present of symptom or mural nodules
 Young patient who can handle the exocrine
and endocrine insufficiency
 Intraductal ultrasonography and
intraoperative pancreatoscopy have been
used to obtain additional information
Michael J, et al. Intraoperative pancreatoscopy. Journal of gastrointestinal surgery 2014;18:1100-07

22. “
”
Branch duct IPMN
(BD-IPMN)

23. Branch duct IPMN (BD-IPMN)
 Incidence of Inv-IPMN and HGD in BD-IPMN is 31%
 Incidence of Inv-IPMN only ~18.5%
 Rate of progression to HGD or invasive cancer 1.4-6.9% per year
Tanaka M, et al. Pancreatology 2017;17:738-53

24. Differentiated pancreatic cyst
Tanaka M, et al. Pancreatology 2017;17:738-53

25. Differentiated pancreatic cyst
Tanaka M, et al. Pancreatology 2017;17:738-53

26. Differentiated pancreatic cyst
Amylase CEA
BD-IPMN
Pseudocyst
SCN
Tanaka M, et al. Pancreatology 2017;17:738-53
Cyst fluid analysis from EUS-FNA

27. Algorithm for
management
of suspected
BD-IPMN
Tanaka M, et al. Pancreatology 2017;17:738-53

28. “
”
Method of resection and
other management

29. Method of resection
Standard pancreatectomy
>> depending on location of lesion
► Pancreatic head
 Pancreaticoduodenectomy
► Pancreatic body or tail
 Distal pancreatectomy
► Diffuse type and MPD dilation along pancreas
 Total pancreatectomy

30. Other treatment
Limit resection (excision, enucleation, uncinatectomy)
 Consider for BD-IPMN without clinical, radiologic,
cytopathogic or serologic suspicion of invasive carcinoma
 Associated with leakage of mucin causing pseudomyxoma
peritonei
 Higher incidence of postoperative pancreatic fistula (POPF)
and recurrence

31. Role of mucosal ablation
 Pancreatic cyst > 2cm, unilocular or oligolocular (no MPD communication)
 Cysts in patient who refuse surgery or are high-risk surgical candidates
 BD-IPMN >> Not recommended..!!
 Cyst resolution rate
 Short term 33-79%
 Complete or partial 75% (median follow up 27 month)
Dewitt JM, et al. Endoscopy 2014;46:457-64
Gomez V, et al. Gastrointes Endosc 2016;83:914-20

32. Role of mucosal ablation
 Complication
 Acute pancreatitis (4.5-10%)
 Abdominal pain (<20%)
 Peritonitis
 Splenic vein obliteration
Steve Pereira, Cystic tumors of the pancreas, London pancreas update meeting 2017

33. Approach to multifocal BD-IPMN
 25-41% of all BD-IPMN
 Treatment as unifocal BD-IPMN
 Segmental resection >> IPMNs with the highest oncological risk
and perform surveillance of the remaining lesions
 Total pancreatectomy >> patients with a strong family history of
pancreatic duct adenocarcinoma (PDAC)
Tanaka M, et al. Pancreatology 2017;17:738-53

34. Follow up
Non-resected
IPMN
Surgically resected
IPMN
 For observe recurrent and progressive of IPMN (non-invasive
IPMN to Inv-IPMN)
 For observe characteristic of cyst >> mural nodule, size and
number
Tanaka M, et al. Pancreatology 2017;17:738-53

35. Follow up of non-resected IPMN
 History and physical examination
 MRI/MRCP (or pancreatic protocol CT)
 EUS (in patient with mural nodule)
 Serum CEA, CA 19-9
Tanaka M, et al. Pancreatology 2017;17:738-53

36. Follow up of non-resected IPMN
 BD-IPMN without high risk stigmata and worrisome features
Size of largest cyst Management
<1 cm
CT/MRI in 6 months then
Every 2 years if no change
1-2 cm
CT/MRI q 6 months x 1 year then
Yearly x 2 then
Every 2 years if no change
2-3 cm EUS q 3-6 months then yearly  alternating MRI with EUS as
Consider surgery in young, fit patient or prolong surveillance
>3 cm
MRI/EUS q 3-6 months
Strongly consider surgery in young, fit patients
Tanaka M, et al. Pancreatology 2017;17:738-53

37. Follow up of non-resected IPMN
 High risk stigmata
 Fit patients - go on surgery
 Unfit patients or high risk for surgery - surveillance q
3-6 month
 Worrisome feature
 Increase risk of invasive carcinoma and HGD
 Short surveillance
Tanaka M, et al. Pancreatology 2017;17:738-53

38. Follow up of non-resected IPMN
 Incidence of the development of concomitant PDAC
 5 year : 3%
 10-year : 8.8%
Uehara H, et al. Gut 2008;57:1561-5.
Tanno S, et al. Pancreas 2010;39: 36-40.
Long-term surveillance over 5 years is necessary for detection
of concomitant PDAC

39. Follow up of surgically resected IPMN
 Non-invasive IPMN with negative surgical margin
 For detect the development of a new IPMN or concomitant PDAC
 CT or MRI at least twice a year in high risk group
 High risks group
 Family history of PDAC
 Surgical margin positive for HGD
 Non-intestinal subtype
 Non high risks group  CT or MRI every 6-12 months
Tanaka M, et al. Pancreatology 2017;17:738-53

40. Follow up of surgically resected IPMN
 Invasive IPMN
 Clinical evaluation, CA19-9, CT whole abdomen with
contrast every 3–6 months for 2 years, then annually
NCCN Guidelines for Pancreatic Adenocarcinoma. v.1.2019

41.  Progression of IPMN within the pancreatic remnant
Jin He, et al. Journal of American College of Surgeons 2013;216:657.

42. Predictors of recurrence
 Presence of HGD in resected specimens
 Margin positive resection
>> conflicting outcomes reported by different centers
(margin positive vs margin negative)
 He et al. (27% vs 22%, p = ns) and Kang et al. (12.1% vs 10.4%, p =
0.704)1
 Marchegiani et al. (25% vs 14%, p = 0.008)
 Family history of PDAC (family history of PDAC vs non-family history of
PDAC)
 He et al. >> recurrent rate 23% vs 7% (p < 0.05)
Jin He, et al. Journal of American College of Surgeons 2013;216:657.
Marchegiani G, et al. Annual of Surgery 2015;261:976-83.

43. Predictors of recurrence
 Ideno et al
 IPMN having concomitant PDAC - gastric subtype
 Miyasaka et al
 Pancreatobiliary subtype of IPMN - predictor for metachronous
development of concomitant PDAC
 Gastric and pancreatobiliary subtypes of IPMN (MUC2- negative non-
intestinal subtype) - should be considered as a high risk for the
development of concomitant PDAC
Idena, et al. Annual of Surgery 2013;258:141-51.
Miyasaka Y, et al. Annual of surgery 2016;263: 1108-14.

44. Surveillance protocol
 Risk of progression of IPMN does not diminish over time following
resection
 Surveillance should continue indefinitely as long as the patient
remains fit for surgery
 In IPMN patients with two or more affected first-degree relatives 
cross-sectional imaging at least twice a year, and surveillance
should not be discontinued as long as the patient remains fit
Wang W, et al. Journal of clinical oncology 2007;25:1417-22.

45. Surveillance protocol
 Genetic defect that associated with increase risk of PDAC
 BRCA2/Fanconi anemia pathway defects (3.5-10 folds)
 Familial atypical mole malignant melanoma syndrome (9-47 folds)
 Peutz-Jeghers syndrome (132 folds)
Couch FJ, et al. Cancer Epidemiol Biomarkers Prev 2007;16:342-6.
Goggins M, et al. Cancer RES 1996;56:5360-4.
Giardiello FM, et al. The New England Journal of Medicine 1987;316:1511-4.

46. Surveillance protocol
 Synchronous and metachronous occurrence of malignant diseases
in extrapancreatic organs in patients with IPMNs occur in 20-30%
 Gastrointestinal cancer  Asian countries
 Skin, breast, and prostatic cancers  United States
 At present  no screening recommendations for detecting
extrapancreatic malignancies
 Once diagnosis of IPMN  consideration of extrapancreatic
neoplasms
Yamaguchi K, et al. European Journal of Surgery 1999;165:223-9.
Reid-Lombardo, et al. Annual of Surgery 2010;251:64-9.
Lee SY, et al. Pancreas 2006;32:186-9.

47. Thank you..