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

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

3. Diagnosis of pancreatic cancer
1- Take clinical context into account 2- Do not trust too much serum markers 3- 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 markers 3- Discuss biopsy - When ? - How ? - What results ? 4- Future demands for biopsy

6. Steinberg Am J Gastroenterol 1990
2- Do not trust too much serum markers
CA 19.9
False -
False +
Causes
. Phenotype Lewis b -
benign cholestasis
chronic pancreatitis (50 %)
liver cirrhosis (60%)
Diabetes
Other cancers :
- biliary (70%), stomach (50%),
colon (30%), oesophagus (10%), non digestive (14%)
Comments
7-10% of the population
No CA 19.9 on cells surface (even when pancreatic cancer)
CA 19.9 not measurable (< 3U/mL)
Values can be very high in common bile duct obstruction whatever cause (> 1000 U/mL)
Diabetes : moderate elevation (2-3N), correlation between CA 19.9 and HbA1c
Magnani J Biol Chem 1982
Steinberg Am J Gastroenterol 1990

7. Steinberg Am J Gastroenterol 1990
2- Do not trust too much serum markers
CA 19.9
False -
False +
Causes
. Phenotype Lewis b -
benign cholestasis
chronic pancreatitis (50 %)
liver cirrhosis (60%)
Diabetes
Other cancers :
- biliary (70%), stomach (50%),
colon (30%), oesophagus (10%), non digestive (14%)
Comments
7-10% of the population
No CA 19.9 on cells surface (even when pancreatic cancer)
CA 19.9 not measurable (< 3U/mL)
Values can be very high in common bile duct obstruction whatever cause (> 1000 U/mL)
Diabetes : moderate elevation (2-3N), correlation between CA 19.9 and HbA1c
Magnani J Biol Chem 1982
Steinberg Am J Gastroenterol 1990

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

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

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

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

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

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

17. Diagnosis of pancreatic cancer
1- Take clinical context into account 2- Do not trust too much serum markers 3- 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)
Type ?
Adenocarcinoma
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)
Type ?
Adenocarcinoma
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)
Type ?
Adenocarcinoma
yes
no (pNET, autoimmune pancreatitis)
Resectable ?
Patient eligible ?
Specific management
yes : surgery envisaged no
Neoadjuvant treatment ?
biopsy
yes no
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
Cytology
Microfragments
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
Cytoponction pancréatique. Expression membranaire intense hENT1 par cellules adénocarcinome
Courtesy Dr J. Cros 26

27. EUS-FNA : more than « usual » histology with EUS-FNA?
Cytoponction pancréatique. Expression membranaire intense hENT1 par cellules adénocarcinome
hENT1
Courtesy Dr J. Cros 27

28. EUS-FNA : could we do more than « usual » histology ?
hENT1
Différents secteurs de la meme tumeur. En haut, expression membranaire intensité modérée de hENT1 par les cellules tumorales. En bas, absence d’expression par les cellules tumorales. Problème possible d’échantillonage par la ponction.
Problem of tumour heterogeneity
Courtesy Dr J. Cros 28

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. Diagnosis of pancreatic cancer remains difficult to assess
Take home messages
Diagnosis of pancreatic cancer remains difficult
to assess
Clinical context is important
Limitations of serum markers and imaging methods
Cytoponction pancréatique. Expression membranaire intense hENT1 par cellules adénocarcinome 31

32. Diagnosis of pancreatic cancer remains difficult to assess
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
Cytoponction pancréatique. Expression membranaire intense hENT1 par cellules adénocarcinome 32