Fernandez del Castillo Gastroenterology 2010 IPMN : the main problem ?
Actual risk of malignancy according to the location : main duct / side branches Mois Main pancreatic duct Side branches 63 % 15 % 0 20 40 60 80 100 0 20 40 60 Levy P et al Clin Gastroenterol Hepatol 2006; 4:460-8 IPMN : actual risk of malignancy Surgery follow-up (guidelines)
Is IPMN malignant ? Predictive factors Sugiyama et al, Br J Surg, 2003; Pais Clin Gastroenterol Hepatol 2007; 5: 489-95; Okabayashi T J Gastroenterol Hepatol 2006;21:462-7 Multivariate analysis, 62 patients operated Mural nodule (RR = 17) diameter Wirsung duct ≥ 7 mm (RR = 5) Multivariate analysis 23 patients diameter wirsung > 10 mm location main duct cyst > 30 mm mural nodule >5 mm Multivariate analysis 74 patients (EUS FNA) age, jaundice, weight loss solid lesion, ductal defect, increased wall thickness Risks : Main duct Wirsung > 7-10mm cyst > 30 mm ? Mural nodule >5 mm
Malignancy and IPMN : Sendai Consensus guidelines Tanaka M Pancreatology 2006;6:17-32 Branch duct (BD)-IPMN : surgical resection BD-IPMN <3 cm if worrisome features : cyst-related symptoms dilated MPD > 6 mm mural nodule BD-IPMN > 3 cm irrespective of symptoms
Validation of criteria for malignant IPMN: guidelines validation
204 patients operated for cystic lesions of the pancreas :
reassessment according to the Sendai guidelines
30 IPMN involving the main pancreatic duct
31 BD-IPMN :
23/31 recommended for surgery (74%)
18/26 adenomas, 5/5 CIS ou invasive carcinoma
8/31 not recommended for surgery
PPV 21 %; NPV 100%
Tang Clin Gastro Hepatol 2008;6:815-19
Summarizing validation of BD-IPMN surveillance… Rautou Clin Gastro Hepatol2008;6:807-14; Salvia Gut 2007;56:1086-90 Tanaka M Pancreatology 2006;6:17-32; Bishop Clin Gastro Hepatol 2008;6:724-25 Over estimation of the risk of malignancy Estimated rate for development and progression 5-10 % High-risk cysts have to better defined Surveillance intervals can probably be increased
No increase in size 91 patients Cyst wall thickening n=3 Surgery in 10 % of patients, no invasive cancer Resection n = 2 Adenoma : n=1 Borderline : n=1 Increase in size 30 patients Suggestive of malignancy n=9 Resection n = 6 In situ carcinoma : n=4 Borderline : n=2 No signs of malignancy n=21 Resection (symptoms) n = 4 Adenoma : n=3 Borderline : n=1 Rautou PA, Levy P, Hammel P, Palazzo L, O’Toole D. Clin Gastroenterol Hepatol 2008 Evolution of branch-duct IPMN under observation 121 patients median follow-up: 3 years
Another problem during the follow-up Fernandez del Castillo Gastroenterology 2010; Ingkakul T Ann Surg 2010; 251:70-5; Uehara D Gut 2008; 51:1561-5 Occurrence of ductal adenocarcinoma irrespective of the BD- IPMN Frequency 1 %/year (11% of concomitant case-series) Due to associated PanIN ? Total pancreatectomy
* First series :
25 patients; lavage 3 to 5 mn (ethanol 5-80%)
35 % cyst diseapparence; 5 patients operated : no epithelium
* association with Taxol injection (ethanol 5-80%)
response 70 % (11/14 patients);
one pancreatitis, 6 hyperamylasemia
* comparative study vs saline injection
42 patients; significant size decrease alcool vs serum salé
cyst healing 33%
Intra-cystic EUS-guided injection of alcohol Gan IS GIE 2005;61: 746-52;Oh HC GIE 2008;67:636-42; Dewitt GIE 2009 total, 81 patients with a 33-70 % efficiency
EUS guided PDT :
. expérimental in live pig : 3 cases , feasable
Pancreas , speeln, kidney without complication
. Protocol study in patients with malignant BD-IPMN
refused for surgery
Chan HH GIE 2004;59:95-9; Yusuf TE GIE 2008;67:957-61 Photodynamic therapy ?
The accuracy of EUS alone is about 50 % with morphological features alones
The accuracy of EUS combined with biological markers might reach 80 % accuracy
The indications for cytology are reduced because the accuracy of cytology is weak except in malignant lesions
Surveillance of side-branched IPMN is based upon the occurrence of mural nodes or enlargment of pancreatic duct. The frequency is 5-10 % but the modalities of this management are still discussed
Incidence cystic lesions of the pancreas (CLP) : Benign , premalignant, malignant ?
2 series with 49 and 212 resected cysts :
malignant 17-20 %
Spinelly et al, Ann Surgery 2004; Fernadez-del Castillo Arch Surg 2003 Fasanella Best Pract Res Clin gastro 2009; Ferrone,C.R. and W. Brugge, Arch Surg 2009 How to manage pancreatic cysts ? Clinical features Imaging : CT scan, MRI, EUS Histology / biological markers : EUS-FNA
FNA and IPMN
FNA accuracy : 42 patients
1- Dilated duct
Cytology (n=19) : accuracy 21 %
2- increased thickness or nodes
Histology (n=23) : accuracy 91 %
83 % without mucus flowing
Maire GIE 2003; 58:701-6
IPMN: intra-cystic markers Distinguishing benign from malignant IPMN, n=41 Maire, Palazzo, O’Toole. Am J Gastroenterol 2008 Cyst fluid CEA of > 200 ng/ml CA 72.4 > 40 U/mL Sensitivity, % 90 88 Specificity, % 71 73 PPV, % 50 47 NPV, % 96 96
Incidence cystic lesions of the pancreas (CLP)
Radiological and surgical series : 1.2% rate
CLP : 1-2% of pancreatic neoplasms
neoplasms : 10-15% of pancreatic cystic masses
Fortuitous discovery (71%)
Surgical resection (prophylactic)
5 years survival 100% ( vs 50-60% if not)
Fasanella Best Pract Res Clin gastro 2009; Gourgiotis J Clin Gastro 2007; Spinelly et al, Ann Surgery 2004; Ferrone,C.R. and W. Brugge, Arch Surg 2009
Classification CLP based upon tumor origin
More comprehensive, less descriptive, less useful ?
Cystic lesions easily diagnosed with modern cross sectional imaging
Typical serous cystadenoma
Typical mucinous cystadenoma
Solid pseudopapillary neoplasm
Unsolved diagnosis with modern cross sectional imaging
Differencial diagnosis between
macrocystic serous cystadenoma,
& non typical mucinous cystadenoma
& non typical pseudocyst
Diagnosis of cystic neuroendocrine tumor
Diagnosis of rare cystic lesions
EUS-FNA Histological analysis Tumor markers Monolayer preparation Amylase, CEA , CA 19-9
Intracystic markers . Amylase, lipase : ductal communication (IPMN) . ACE : the best < 5 ng/mL : serous cystadenoma > 400 ng/mL : mucinous lesion . Ca 19-9 : mucinous cystadenoma, malignant progression > 50000 U/ml MCA vs others 15% sens; 81 % spec MCA with carcinoma: 86% sens; 85% spec . Ca 72.4 : mucinous cystadenoma, malignant progression . Mucines M1 : disappointing, Ki-ras : disappointing Frossard Am J Gastroenterol 2003;Hammel GCB 2002; Van der Vaaij GIE 2005; Tada Clin Gastro 2006 Amylase, ACE CA19-9 low = SCA ACE > 400 ng/ml = mucinous (K++)
Histology AND cytology !
Diagnostic yield : < 30 %
Better if cancer present
Cystadenocarcinoma: 50-60 %
How do we optimise the biopsy?
Provide adequate information for pathologist ++
Combine cytology and histology
Pancreatic Cystic Tumors & biopsy Fabre M. Acta Endoscopica 2002
Gastric- Foveolar type Villous-intestinal type Pancreatobiliary type
Typical features Dilated main pancreatic duct And/or Branched cystic lesion
IPMN different types Branch duct type Malignancy 5-15% Combined type Malignancy >50% Main duct type Malignancy >50%
EUS-FNAB for patients with IPMN ? Maire, O’Toole, Palazzo Gastrointest Endosc 2003:701-6. Cytology – diagnosis of IMPN (n=18) Histology - IPMN (n=24) Side branch without nodule IPMN with nodule and mass
IMPN surveillance : unsolved questions
Regarding modalities :
frequency : annual, every two years ?
modalities : MRI only ? EUS or EUS-FNA associated ?
Regarding risk of malignancy :
All IPMN precursors to malignancy ?
Different speed course for progression ?
Role of symptoms in the risk of malignancy ?
Role of size ?
(Do BD-IPMN >30 mm without mural node require surgery ?)
role of environnmental factors or genetic disease ?
Tanaka M Pancreatology 2006;6:17-32; Bishop Clin Gastro Hepatol 2008;6:724-25
How to perform EUS-guided FNA in cystic pancreatic tumors ?
Puncture in one quick shot
Avoid the MPD and vessels
Use the shorter way (bending & elevator up)
But go through the pancreas ( uncinate process) to avoid fistula in case of IPMN.
Use 22 G needle in the majority of the cases
How to perform EUS-guided FNA in cystic pancreatic tumors ?
Start with fluid analysis (≥1ml for markers,≥1ml for cytology) & follow with septa and wall (avoid to go through the distal wall)
Empty the cyst if it is possible to improve the cytological (thin-prep® method on the last ml) analysis & better vizualise the wall & the landmarks between the cyst & the MPD
When less than 1ml ,prefer CEA. .
Provide IV antibiotics ( amoxicilin + clavulanic acid before starting and 6 h later. Add per-oral antibiotics during 5 days in case of pseudo-cyst with necrosis) even there is no graded data in the literature
Weak complication rate :
2 to 5% (2 series with solid pancreatic masses 90 and 216
Voss Gut 2000; Raut J Gastrointest Surg; O Toole Gastrointest endosc 2001
Summarizing validation of BD-IPMN surveillance… Rautou Clin Gastro Hepatol2008;6:807-14; Salvia Gut 2007;56:1086-90 Tanaka M Pancreatology 2006;6:17-32; Bishop Clin Gastro Hepatol 2008;6:724-25 Over estimation of the risk of malignancy Estimated rate for development and progression 5-10 % High-risk cyts have to better defined Surveillance intervals can probably be increased