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Pancreatic cancers

Lecture for students
by

Chang Min Cho

on 14 August 2016

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Transcript of Pancreatic cancers

Kyungpook National University Medical Center
Department of Hepatobiliary and Pancreatic cancer
Pancreatic cancer
Cho Chang-Min
Cancer prevalence in 2009
Cancer-related death rate in 2010
5-year survival rate of cancer
Poor prognosis
no specific symptom
advanced stage at initial diagnosis
associated symptoms (abdominal pain, jaundice, weight loss)
incidental finding
early stage at initial diagnosis
no specific symptom
below 10%
10-20%: resectable

overall 5 year survival rate: < 5% - 10%
Pancreatic cancer
Demographic factor
age, gender, nationality
Environmental (host) factor
obesity, smoking, diabetes
Hereditary (genetic) predisposition
familial pancreatic cancer
familial multi-organ cancer syndrome
hereditary pancreatitis
Risk factors
Age: 80% in 60-80 yrs
Male gender
Ashkenazi Jewish descent
African-American descent
Demographic factors
smoking
25% of pancreatic cancer
OR of 2.13 with more than 50 pack*years
increased risk with
familial pancreatic cancer (x3.7)
hereditary pancreatitis (x2)
obesity
OR of 2.58
diabetes
less clear (OR of 1.82)
primary cause vs. secondary endocrine dysfunction
recently diagnosed (less than 4 year): OR of 2.1
long standing diabetes (5 year or more): OR of 1.5
Host factors
Familial pancreatic cancer
10% of pancreatic cancer
history of first degree relatives with pancreatic cancer
2 members affected: x18
3 members affected: x57
suitable candidate for screening
Familial multi-organ cancer syndrome
BRCA2: breast and ovarian cancer
CDKN2A: familial atypical multiple mole melanoma
STK11/LKV1: Peutz-Jeghers syndrome
Hereditary pancreatitis
PRSS1
Genetic predisposition
Precancerous lesions
PanIN (pancreatic intraepithelial neoplasia)
Mucinous cystic neoplasm
IPMN (intraductal papillary mucinous neoplasm)
Cancer sequence
Cancer sequence
Tumor marker
CEA
CA19-9
Screening and Early detection
Ca19-9
87%: increased in pancreatic cancer

Health screening examination
Duration: from Dec. 1994 to Jul. 1996
Enrollment: 11,974
> 37 U/mL: 179 (1.5%)
pancreatic cancer: 2%
positive predictive value: 0.98%

tumor associated antigen, not tumor-specific
synthesized by other organs
pancreas, bile duct
gastric, colonic, endometrial, and salivary gland

not useful for screening asymptomatic populations
Tumor markers for screening
No ideal single screening test
useful to diagnose large pancreatic cancer (> 2 cm in size)
advanced and unresectable stage

most sensitive modalities
EUS and multidetector CT

EUS
preferred modality
superior in sensitivity, specificity and accuracy
ability to perform EUS-FNA
Imaging modalities
Early 1980s
alternative diagnostic modality to USG
USG: limited depth of penetration and image interference
technical advances over last 20 years
linear array echoendoscopy
color flow/Doppler
evolved to interventional procedure

EUS abnormalities for screening
cystic or mass lesion

EUS-FNA
cytological sampling of abnormal area
high accuracy (92%)
EUS as a screening tool
General population: no cost-effective

Screening candidate for high risk group
familial pancreatic cancer
> 2 first-degree relatives with pancreatic cancer
hereditary pancreatitis
familial multi-organ cancer syndrome
FAMMM
Peutz-Jeghers syndrome

Modality
tumor marker + image (CT and/or EUS)
Screening and Early detection
obstructive jaundice
common in periampullary tumor
abdominal discomfort, pruritus, lethargy and weight loss
less common symptoms
epigastric pain, backache, new onset DM
acute pancreatitis
nausea and vomiting due to gastroduodenal obstruction
Clinical presentation
jaundice and cachexia
scratch marks due to pruritus
palpable gallbadder (Courvoisier's sign)
sign of malignant biliary obstruction
distant metastasis
hepatomegaly
ascites
left supraclavicular lymphadenopahty (Virchow's node)
periumbilical lymphadenopathy (Sister Mary Joseph's nodes)
Physical signs
Imaging modalities
Tissue diagnosis and cytology
Serum markers
Diagnosis
Objective
to confirm the presence of tumor
to differentiate mass between inflammatory and malignancy
to predict prognosis
localized vs. distant metastasis

Computed tomography (CT)
dual phase, contast-enhanced spiral CT
imaging modality of choice
MRI/MRCP
no advantage over CT
benefit to characterize the nature of liver metastasis
to evaluate the cause of biliary obstruction with no obvious mass
ERCP
EUS
highly sensitive in detecting small lesion (< 3cm)
useful in assessing vascular invasion and LN involvement
PET-CT
Imaging modalities
Not always necessary in operable pancreatic cancer

EUS-FNA
technique of choice
before neoadjuvant treatment
90% in accuracy
minimal risk of intraperitoneal dissemination

Percutaneous biopsy
primary tumor or liver metastatic lesion
inoperable or metastatic disease

ERCP
ductal brushing
diagnostic value of pancreatic juice sampling: 25-30%
Tissue diagnosis and Cytology
CA19-9
elevated in 70-80% of pancreatic cancer
inadequate for screening and diagnosis
preoperative level: correlated with tumor stage
postresection level: prognostic value
response in chemotherapy
Serum markers
AJCC TNM staging system
location and size of the tumor
involvement of LN
distant metastasis

resectable
locally advanced
unresectable without distant spread
metastatic
Staging
Resectable disease

Inoperable locally advanced disease

Metastatic disease
Treatment: pancreatic cancer
10%: potentially suitable for surgical resection
R0 resection with adjuvant treatment
best chance of cure
median survival: 20-23 months
5-year SR: 20%
favorable outcome
small tumor (< 3cm)
well-differentiated tumor
no involvement of LN

postoperative chemotherapy or CRT
improvement of long-term outcomes
Resectable disease
30% of pancreatic cancer
median survival with gemcitabine: 9 months
Inoperable locally advanced disease
60% of pancreatic cancer
gemcitabine
standard treatment
median survival: 6 months
1-year SR: 20%

gemcitabine-based combination therapy
erlotinib: tyrosine kinase inhibitor
capecitabine: no survival benefit

FOLFIRINOX
5FU/FA, irinotecan and oxaliplatin
increased toxicity
indicated at good performance status
Metastatic disease
Lee KT et al. Kor J Int Med 1997
Shi et al. Clin Cancer Res 2009
Brune et al Am J Surg Pathol 2006
Detlefsen et al Virchow Arch 2005
Bile duct tumor (cholangiocarcinoma)
Intrahepatic
Perihilar (Klatskin tumor)
Extrahepatic
Gallbladder tumor
Pancreatic cancer
Ampulla of Vater tumor
Pancreato-biliary tumors
PanIN and IPMN
more common in patients with family hx of pancreatic cancer
resected specimen in patients with FPC
PanIN associated with lobular atrophy of surrounding parenchyma

animal study
PanIN producing multiple foci of small duct obstruction
progression to multifocal lobulocentric atrophy

abnormal findings of EUS
cyst or mass
chronic pancreatitis-like change
국가암정보센터
K-RAS
p16
p53
DPC4
BRCA2
Biomarker
K-ras
p53
CDKN2A (p16)
Imaging modality
USG
CT
MRI/MRCP
ERCP
EUS
PET-CT
Phase III studies of adjuvant chemotherapy in resected pancreatic cancer






Study group






PFS/DFS
(mon)




Survival

Median p value
(mon)






HR
p value










ESPAC 1 (2004)










CTx (5FU+FA) 15.3










0.02










20.1 0.71











(n=550)











None 9.4 14.7











0.009













CONKO 001 (2007)













Gemcitabine 13.4














< 0.001













22.1 N/A















(n=368)















None 6.9 20.2















0.06

















ESPAC 3 (2010)

















5FU/LV


















N/A

















23 0.94


















(n=1088)


















Gemcitabine 23.6


















0.39
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