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ESMO, Barcelona, 3 July 2013

ESMO, Barcelona, 3 July 2013. Pascal HAMMEL, MD, PhD Department of Gastroenterology- Pancreatology Hôpital Beaujon 92110 Clichy France pascal.hammel@bjn.aphp.fr. The optimal algorithm for diagnosis and for obtaining a biopsy in pancreatic cancer. Disclosure form.

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ESMO, Barcelona, 3 July 2013

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  1. ESMO, Barcelona, 3 July 2013 Pascal HAMMEL, MD, PhD Department of Gastroenterology- Pancreatology Hôpital Beaujon 92110 Clichy France pascal.hammel@bjn.aphp.fr The optimal algorithm for diagnosis and for obtaining a biopsy in pancreatic cancer

  2. Disclosure form No conflict of interest in relation with this lecture

  3. Diagnosis of pancreatic cancer 1- Take clinical context into account2- Do not trust too much serum markers3- Discuss biopsy - When ? - How ? - What results ?4- Future demands for biopsy

  4. 1- Take clinical context into account - Differential diagnosis can be difficult, consequences of errors very deleterious- Importance of : age, general status, tobacco/alcohol consumption, history of pancreatitis, changes in weight, diabetes, familial history of cancers (digestive, gynecologic, skin)

  5. Diagnosis of pancreatic cancer 1- Take clinical context into account 2- Do not trust too much serum markers3- Discuss biopsy - When ? - How ? - What results ?4- Future demands for biopsy

  6. 2- Do not trust too much serum markers SteinbergAm J Gastroenterol 1990 Magnani J Biol Chem 1982

  7. 2- Do not trust too much serum markers SteinbergAm J Gastroenterol 1990 Magnani J Biol Chem 1982

  8. 2- Do not trust too much serum markers Insuffisant validation,feasibility in routine practice, problems of sensitivity/specificity - KRAS (Maire, BJC 1998)- p53(Hammel, Gut 1997) - Circulating tumor cells(Iwanicki-Caron I Am J Gastroenterol 2013,Clement-Bidard Ann Oncol 2013)- Others :CYFRA 21-1(Boeck, BJC 2013), miR-27a-3p(Wang, Cancer PrevRes 2013), LCN2/TIMP1 (Slater, Translational Oncology 2013), serum metabolomics (Kobayashi, Cancer Epidemiol Biomarkers Prev 2013), PAM04 (Gold DV, ASCO GI 2010)… or specificity with jaundice(Tonack S, BJC 2013)

  9. 2- Can we trust imaging methods ? Pseudotumour : length of MPD stenose CBD MPD CBD MPD • Cancer • Short /complete • Same level CBD Focal pancreatitis - Long/incomplete - Different level CBD PMPD : Main pancreatic duct CBD : common bile duct

  10. Suspicion of cancer on MRI : pitfall Suspect « stop » and upstream enlargement of MPD

  11. Suspicion of cancer on MRI : pitfall CT CT To detect calcifications in chronic pancreatitis : CT scan >MRI

  12. Chronic pancreatitis often present beside a cancer… In a segment of pancreas, focal enlargement of main pancreatic duct upstream a mass … Chronic pancreatitis : risk factor for cancer(x 10-15) Pancreatic mass on imaging : pancreatitis or cancer ? Relative risk high….but less than 5% of patients with old CP Chronic pancreatitis silent for long time becomes symptomatic again Calcifications are «pushed » around the mass Extrapancreatic spreading of the tumour

  13. PET-18FDG Sensitivity and specificity in cancer do not exceed 80% 2- Can we trust imaging methods ? Schick, Eur J Med Mol Imaging 2008 Kartalis Eur Radiol 2009: Dietrich Clin Gastroenterol Hepatol 2008

  14. PET-18FDG Sensitivity and specificity in cancer do not exceed 80% Strong and diffuse signal in some benign pancreatitis False negatives in diabetes 2- Can we trust imaging methods ? Steroid test Schick, Eur J Med Mol Imaging 2008 Kartalis Eur Radiol 2009: Dietrich Clin Gastroenterol Hepatol 2008

  15. 2- Can we trust imaging methods ? Endoscopic Ultrasonography (EUS) in experienced hands remains one of the best tools for diagnosis Locally advanced cancer (biopsy) Courtesy Dr Palazzo Screening of relative at risk for pancreatic cancer : islet of Pan-IN 3

  16. 2- Can we trust imaging methods ? • Contrast (E)US • Hypovascularization 57/62 • Differential diagnosis AIP/pNET • Elastometry EUS Courtesy Dr L. Palazzo

  17. Diagnosis of pancreatic cancer 1- Take clinical context into account 2- Do not trust too much serum markers3- Discuss biopsy - When ? - How ? - What results ?4- Future demands for biopsies

  18. Pancreatic tumour and biopsy : why ? Gut 2008;57:1646-7 Unappropriate resection for pancreatitis Propose steroids in a patient with cancer 1- Adenocarcinoma is much more frequent than pseudotumoral pancreatitis ! 2- Do not hesitate to perform biopsy when doubtful

  19. Pancreatic tumour and biopsy : when ? Pain, jaundice Imaging (US, CT, MRI, /+-EUS) : mass Benign or malignant ? Likely malignant (local signs, metastases) Adenocarcinoma Type ? no (pNET, autoimmune pancreatitis) Specific management

  20. Pancreatic tumour and biopsy : when ? Pain, jaundice Imaging (US, CT, MRI, /+-EUS) : mass Benign or malignant ? Likely malignant (local signs, metastases) Adenocarcinoma Type ? yes no (pNET, autoimmune pancreatitis) Resectable ? Patient eligible ? Specific management no Biopsy Chemotherapy (CRT) or BSC

  21. Pancreatic tumour and biopsy : when ? Pain, jaundice Imaging (CT, MRI, EUS) : mass Benign or malignant ? Likely malignant (locoregional signs, metastases) Adenocarcinoma Type ? yes no (pNET, autoimmune pancreatitis) Resectable ? Patient eligible ? Specific management yes : surgery envisaged no Neoadjuvant treatment ? biopsy no yes Chemotherapy/BSC biopsy resection

  22. Pancreatic cancer : remind the limits of pathology EUS-FNA Cytology Conventional monolayer Courtesy Pr Couvelard

  23. Pancreatic cancer : remind the limits of pathology EUS-FNA Microfragments Cytology Conventional monolayer Histology « cell-block » Conventional histology Informations needed : clinical context, conditions of FNA Courtesy Pr Couvelard

  24. Pancreatic cancer : remind the limits of pathology Often poor material Mucus Blue Alcian

  25. Pancreatic tumour and biopsy : how ? EUS-fine needle aspiration is not always the best tool !

  26. Biopsy : more than « usual » histology ? • In the near future, to only assess cancer will not be sufficient… • Informations required for predictive, prognostic markers Courtesy Dr J. Cros

  27. EUS-FNA : more than « usual » histology with EUS-FNA? hENT1 Courtesy Dr J. Cros

  28. EUS-FNA : could we do more than « usual » histology ? hENT1 Problem of tumour heterogeneity Courtesy Dr J. Cros

  29. EUS-FNA : could we do more than « usual » histology ? SPARC in the stroma and nab-paclitaxel Mantoni T et al, Cancer Biology and Therapy 2008

  30. EUS-FNA : could we do more than « usual » histology ? Biological differences between primary and metastases ? Changes during the course of disease ?

  31. Take home messages • Diagnosis of pancreatic cancer remains difficult • to assess • Clinical context is important • Limitations of serum markers and imaging methods

  32. Take home messages • Diagnosis of pancreatic cancer remains difficult • to assess • Clinical context is important • Limitations of serum markers and imaging methods • Most convenient route for biopsy and • close collaboration with pathologist • Future: optimise analyses of material obtain

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