Download Pancreatic cancer

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
[email protected]
Disclosure form
No conflict of interest in relation with this lecture
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
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)
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
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 (23N), 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 (23N), 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
Res 2013),
(Wang, Cancer Prev
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)
2- Can we trust imaging methods ?
Pseudotumour : length of MPD stenose
CBD
MPD
CBD
MPD
Focal pancreatitis
Cancer
- Long/incomplete
- Short /complete
- Different level CBD
- Same level CBD
PMPD : Main pancreatic duct
CBD : common bile duct
Suspicion of cancer on MRI : pitfall
Suspect « stop » and upstream enlargement of MPD
Suspicion of cancer on MRI : pitfall
CT
CT
To detect calcifications in chronic pancreatitis : CT scan > MRI
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
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
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
Steroid test
– False negatives in diabetes
Schick, Eur J Med Mol Imaging 2008
Kartalis Eur Radiol 2009:
Dietrich Clin Gastroenterol Hepatol 2008
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
2- Can we trust imaging methods ?
• Contrast (E)US
– Hypovascularization 57/62
– Differential diagnosis AIP/pNET
• Elastometry EUS
Courtesy Dr L. Palazzo
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
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
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
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 ?
no
Biopsy
Chemotherapy (CRT) or BSC
Specific management
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 ?
Specific management
Patient eligible ?
no
yes : surgery envisaged
Neoadjuvant treatment ?
biopsy
yes
no
biopsy
resection
Chemotherapy/BSC
Pancreatic cancer : remind the limits of pathology
EUS-FNA
Cytology
Conventional
monolayer
Courtesy Pr Couvelard
Pancreatic cancer : remind the limits of pathology
EUS-FNA
Cytology
Conventional
monolayer
Microfragments
Histology
« cell-block »
Informations needed : clinical context, conditions of FNA
Conventional
histology
Courtesy Pr Couvelard
Pancreatic cancer : remind the limits of pathology
Often poor material
Mucus
Blue Alcian
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?
hENT1
Courtesy Dr J. Cros
EUS-FNA : could we do more than « usual » histology ?
hENT1
Problem of tumour heterogeneity
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 difficult
to assess
• Clinical context is important
• Limitations of serum markers and imaging
methods
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