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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. - PowerPoint PPT Presentation
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ESMO, Barcelona, 3 July 2013
Pascal HAMMEL, MD, PhD
Department of Gastroenterology- Pancreatology Hôpital Beaujon
92110 ClichyFrance
pascal.hammel@bjn.aphp.fr
The optimal algorithm for diagnosis and for obtaining a biopsy in pancreatic
cancer
Disclosure form
No conflict of interest in relation with this lecture
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
Diagnosis of pancreatic cancer
- 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)
1- Take clinical context into account
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
Diagnosis of pancreatic cancer
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
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
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)
Focal pancreatitis
- Long/incomplete
- Different level CBD
Cancer
- Short /complete
- Same level CBD
Pseudotumour : length of MPD stenose
PMPD : Main pancreatic duct CBD : common bile duct
CBDMPD CBD
MPD
2- Can we trust imaging methods ?
Suspicion of cancer on MRI : pitfall
Suspect « stop » and upstream enlargement of MPD
To detect calcifications in chronic pancreatitis : CT scan > MRI
Suspicion of cancer on MRI : pitfall
CT CT
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
• 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
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 diabetesSchick, Eur J Med Mol Imaging 2008
Kartalis Eur Radiol 2009:Dietrich Clin Gastroenterol Hepatol 2008
2- Can we trust imaging methods ?
Steroid test
Locally advanced cancer (biopsy)
Screening of relative at risk for pancreatic cancer : islet of Pan-IN 3
Endoscopic Ultrasonography (EUS) in experienced hands remains one of the best tools for diagnosis
2- Can we trust imaging methods ?
Courtesy Dr Palazzo
• Contrast (E)US– Hypovascularization 57/62– Differential diagnosis AIP/pNET
• Elastometry EUSCourtesy Dr L. Palazzo
2- Can we trust imaging methods ?
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
Diagnosis of pancreatic cancer
Gut 2008;57:1646-7
Unappropriateresectionfor pancreatitis
Propose steroidsin a patient with cancer
1- Adenocarcinoma is much more frequent than pseudotumoral pancreatitis !
2- Do not hesitate to perform biopsy when doubtful
Pancreatic tumour and biopsy : why ?
Pain, jaundice
Imaging (US, CT, MRI, /+-EUS) : mass
Benign or malignant ?
Likely malignant (local signs, metastases)
Type ? Adenocarcinoma
Specific management
Pancreatic tumour and biopsy : when ?
no (pNET, autoimmune pancreatitis)
Pain, jaundice
Imaging (US, CT, MRI, /+-EUS) : mass
Benign or malignant ?
Likely malignant (local signs, metastases)
Resectable ?Patient eligible ?
no
Chemotherapy (CRT) or BSC
Type ? Adenocarcinoma
yes
Specific management
Biopsy
no (pNET, autoimmune pancreatitis)
Pancreatic tumour and biopsy : when ?
Pancreatic tumour and biopsy : when ?
Pain, jaundice
Imaging (CT, MRI, EUS) : mass
Benign or malignant ?
Likely malignant (locoregional signs, metastases)
Resectable ?Patient eligible ?
Neoadjuvant treatment ?
no
yes
biopsy
no
resectionChemotherapy/BSC
yes : surgery envisaged
Type ? Adenocarcinoma
no (pNET, autoimmune pancreatitis)yes
Specific management
biopsy
Conventional
EUS-FNA
Cytology
monolayer
Courtesy Pr Couvelard
Pancreatic cancer : remind the limits of pathology
Conventional Conventionalhistology
EUS-FNA
Cytology Microfragments
monolayer Histology « cell-block »
Courtesy Pr CouvelardInformations needed : clinical context, conditions of FNA
Pancreatic cancer : remind the limits of pathology
Blue Alcian
Mucus
Pancreatic cancer : remind the limits of pathology
Often poor material
Pancreatic tumour and biopsy : how ?
EUS-fine needle aspiration is not always the best tool !
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
EUS-FNA : more than « usual » histology with EUS-FNA?
hENT1Courtesy Dr J. Cros
hENT1
Problem of tumour heterogeneity
EUS-FNA : could we do more than « usual » histology ?
Courtesy Dr J. Cros
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
EUS-FNA : could we do more than « usual » histology ?
Biological differences between primary and metastases ?
Changes during the course of disease ?
Take home messages
• Diagnosis of pancreatic cancer remains difficultto assess
• Clinical context is important
• Limitations of serum markers and imaging methods
Take home messages
• Diagnosis of pancreatic cancer remains difficultto assess
• Clinical context is important
• Limitations of serum markers and imaging methods
• Most convenient route for biopsy andclose collaboration with pathologist
• Future: optimise analyses of material obtain
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