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Endoscopy in Gastrointestinal Oncology - Slide 10 - M. Barthet - Management of cystic lesions of the pancreas
 

Endoscopy in Gastrointestinal Oncology - Slide 10 - M. Barthet - Management of cystic lesions of the pancreas

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  • Depuis la dernieres décénie, En raison surtout de l’émergeance des diff techniques d’imagerie, on remarque une réelle aug incidence des kystes ad 1 % des pts hospit. Certains dogmes ont été remis en question...en particulier la fréquence des pseudoKystes L’histoire naturelle demeure mal définie mais l’on sait avec certitude que certaines de ces lésions ont un potentiel d’évolution vers une néoplasie invasive. L’on sait également que lorsque réséqués précocément, au stade pré-néoplasique, la survie
  • Pour illustrer l’incidence des différentes lésions ksytiques, voici une série récemment publiée de 256 spécimens chirurgicaux avec les dxd Dans cette série ad 50% des lésions étaient malignes ou pré-malignes (Cis, borderline)...ce qui illustre le réel potentiel malin des lésions kystiques
  • 1- Globalement évaluation pré-opératoire demeure sous optimale car bcp de chevauchement a\\n morphologie (ex kyste uniloc et pancréatite = IPMN vs pseudoK) Apparence macrocystique ad 20-25% des SCN (séreux) 2-Pancréatoscopie (projections papillaires –Main duct type et extension intra-canalaire) et IDUS yield élevé 3- ERCP limité évaluation papille (anomalies canalaires non sp)
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  • 1
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  • Depuis la dernieres décénie, En raison surtout de l’émergeance des diff techniques d’imagerie, on remarque une réelle aug incidence des kystes ad 1 % des pts hospit. Certains dogmes ont été remis en question...en particulier la fréquence des pseudoKystes L’histoire naturelle demeure mal définie mais l’on sait avec certitude que certaines de ces lésions ont un potentiel d’évolution vers une néoplasie invasive. L’on sait également que lorsque réséqués précocément, au stade pré-néoplasique, la survie
  • Depuis la dernieres décénie, En raison surtout de l’émergeance des diff techniques d’imagerie, on remarque une réelle aug incidence des kystes ad 1 % des pts hospit. Certains dogmes ont été remis en question...en particulier la fréquence des pseudoKystes L’histoire naturelle demeure mal définie mais l’on sait avec certitude que certaines de ces lésions ont un potentiel d’évolution vers une néoplasie invasive. L’on sait également que lorsque réséqués précocément, au stade pré-néoplasique, la survie
  • Depuis la dernieres décénie, En raison surtout de l’émergeance des diff techniques d’imagerie, on remarque une réelle aug incidence des kystes ad 1 % des pts hospit. Certains dogmes ont été remis en question...en particulier la fréquence des pseudoKystes L’histoire naturelle demeure mal définie mais l’on sait avec certitude que certaines de ces lésions ont un potentiel d’évolution vers une néoplasie invasive. L’on sait également que lorsque réséqués précocément, au stade pré-néoplasique, la survie
  • 1
  • 1

Endoscopy in Gastrointestinal Oncology - Slide 10 - M. Barthet - Management of cystic lesions of the pancreas Endoscopy in Gastrointestinal Oncology - Slide 10 - M. Barthet - Management of cystic lesions of the pancreas Presentation Transcript

  • Management of cystic lesions of the pancreas Marc Barthet, Hôpital Nord, Marseille, France Roma, 11-12 March 2011
  • Cystic tumor of the pancreas : an increased frequency ?
    • Incidental cystic tumors :
    • US series : 1/5000 US examination
    • CT scan series: 1% out of CT scan
    Incidental cystic tumors 0,05 to 1% of pancreatic imaging series Singh Pancreas 2007; Barthet Endoscopy 2007 Allen PJ. Ann Surg 2006 Series 539 incidental cystic lesion
  • Distribution of cystic lesion
    • Surgical series 60 patients
    • incidental symptom
    • SCA 12 (55%) 4 (11%)
    • MCA 3 (14%) 2 (5%)
    • Invasive MCA 0 2 (5%)
    • Benign IPMN 4 (18%) 11 (29%)
    • In situ carcinoma IPMN 2 (9%) 7 (18%)
    • Invasive IPMN 1 (4,5%) 12 (32%)
    Hardacre Am J Surg 2007 More frequent incidental cystic tumor : SCA and MCA Incidental cystic lesions are more likely to be benign (compared to symptom) > <
  • Classification cystic lesions of the pancreas (CLP) :
    • Neoplastic / non neoplastic cysts
    • WHO classification
    • (World health organization 1996)
    Fasanella Best Pract Res Clin gastro 2009; Basturk O Arch Pathol Lab Med 2009 90 % Neoplastic cysts
  • C.R. Ferrone, W. Brugge, Arch Surg 2009 SCA : 13%; MCA : 18%; IPMN : branch duct 23%; main duct 25%; SPT 5% Endocrine 4% Others 10%
  • The problem with cystic tumor of the pancreas
    • Is to differenciate…
    • mucinous lesion with potential risk of malignancy (IPMN, MCA) or cystic endocrine tumor
          • From..
    • cystic lesions without risk of malignancy (SCA or PC)
    ENETS Guidelines Neuroendocrinology 2006; Singh Pancreas 2007; Barthet Endoscopy 2007
  • Risk of malignancy Serous cystadenoma Branch duct IPMN Mucinous cystadenoma Solid pseudo papillary neoplasm Main duct IPMN 0% 5-15% >30% >50% Singh Pancreas 2007; Barthet Endoscopy 2007
  • Imaging
    • U/S transabdominal
      • Identification & localization
    • CT > MRI better resolution
    • MRCP > for delineating duct
      • Cyst -duct communication
    • EUS
      • Better examination of the pancreas and characterization of mural nodes
        • Interobserver’s variability ( к = 0,46)
    Visser, AJR 2007 ; Kubo, Am J Gastro 2001; Brugge , Gastro 2003;Khalid, Clin Gas Hepatol 2005 Imaging alone is not sufficient to predict # Malignant vs benign Mucinous vs no-mucinous
  • Oh et al Am J Gastro 2008
  • Oh et al Am J Gastro 2008 CT: accuracy 54-93 %
  • Oh et al Am J Gastro 2008 EUS without FNA : accuracy 40-93%
  • Oh et al Am J Gastro 2008 CEA : < 4 = SCA CEA : > 300/400 = MCA
  • Criteria at EUS vs. final diagnosis (n=67) Frossard, Amouyal, Amouyal, Palazzo et al Am J Gastroenterol 2003;98:1516 Performance of EUS : morphology alone Diagnosis N Se. Sp. PPV NPV Pseudocyst 6 100 100 100 100 Serous cystadenoma 14 43 76 32 83 Mucinous cystadenoma 17 65 84 58 87 IPMN 14 100 100 100 100 Cystic neuroendocrine T. 6 33 100 100 93 Cystadenocarcinoma 9 88 96 80 93 Pseudosolid & papillary 1 100 100 100 100
  •  
  • Performance of EUS, cytology, markers
    • Multicentric EUS study – « mucinous lesion »
      • EUS, tumor markers, and cytology 1
        • mucinous (n=68) ; serous (n=7); pseudocyst (n=27) ;
        • neuroendocrine T (n=5) , other (n=5)
    Brugge et al Gastroenterology 2004;26:1330 Diagnostic accuracy, % p EUS features 51% * p < 0,05 Intra-cystic CEA levels 80% * Cytology 59%
  • Cytology Frossard Am J Gastroenterol 2003;98:1516 SC MC Van der Vaaij. Gastrointest Endosc 2005 Diagnostic yield <30%
  • Van der Vaaij. Gastrointest Endosc 2005 * CEA > 400 ng/mL MC/MCA se 57% sp 99% * CEA < 5 ng/mL Serous cystadenoma se 92% sp 87% CEA * Beaujon
  • Van der Vaaij. Gastrointest Endosc 2005 CA 19.9 Beaujon >50 000 U/mL MC/MCA se 72% sp 84%
  • Other markers ?
    • CA 72.4
      • Good (~CEA), less accessible
    • CA 15.3
      • Not well evaluated
    • Mucins M1
      • Deception : >1200 U/mL MC/MCA (se : 41% ; sp : 93 %)
      • Contamination by FNA route … trans-gastric
      • Not easily available
    • K-ras
      • Malignant lesions only, not readily available
      • Viscosity: reproducibility ?
  • Brugge WR. Gastroenterology 2004 Summary 50% 80% Cytology Imaging EUS Liquid (CEA) 90%
  • 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
    • 8 adenomas
    • 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
    • 3series
    • * 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 ?
  • Conclusion
    • 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 :
    • Benign 21-41%
    • premalignant 42-51%
    • 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
    • Clinical features
      • Fortuitous discovery (71%)
      • Asymptomatic (37-58%)
    • Natural history
      • 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 ?
    Basturk O Arch Pathol Lab Med 2009 Inflammatory –related cysts pseudocyst, cystic dystrophy of heterotopic pancreas Neoplastic cysts ductal lineage : mucinous serous endocrine lineage Acinar lineage Endothelial lineage Undetermined lineage Congenital cysts Miscellaneous cysts pseudocysts IPMN, MCA SCA Cystic Endocrine tumor Lymphoepithelial cyst Duplication cysts Acinar cell Cadenoma/CC Lymphangioma Solid pseudopapillary N
  • Which role for diagnostic EUS ± EUS-guided FNA ?
    • Cystic lesions easily diagnosed with modern cross sectional imaging
    • Typical pseudocyst
    • Typical serous cystadenoma
    • Typical mucinous cystadenoma
    • IPMN
    • Cystadenocarcinoma
    • 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 !
      • Pauci-cellular samples
      • Diagnostic yield : < 30 %
      • Better if cancer present
        • Cystadenocarcinoma: 50-60 %
        • IPMN: 80%
    • How do we optimise the biopsy?
      • Provide adequate information for pathologist ++
      • Combine cytology and histology
        • Thinprep ®
    Pancreatic Cystic Tumors & biopsy Fabre M. Acta Endoscopica 2002
  • IPMN
    • Adenoma
    • Borderline
    • In Situ
    • Invasive
    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
  • Morbidity
    • Weak complication rate :
    • 2 to 5% (2 series with solid pancreatic masses 90 and 216
    • patients)
    • bleeding, infection, acute pancreatitis, perforation
    • increased with cystic tumor
    • Problem of cystic lesion:
    • 134 solid tumors (head 95; body 39)
    • 2,5 passages
    • no complication
    • 114 cystic tumors: 4 complications
    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