Pancreatic cancer

dr. Tjatur Winarsanto SpPD

Pathology

 Exocrine
 Solid
 Infiltrating ductal adenocarcioma: most
 Variant of ductal adenocarcinoma
 Signet-ring cell, medullary, adenosquamous, anaplastic
 Acinar cell carcinoma
 Pancreatoblastoma

 Cystic
 Endocrine
Pathology

 Exocrine
 Solid
 Cystic
 Mucinous cystic neoplasm
 Intraductal papillary mucinous neoplasm

 Serous cystic neoplasm

 Solid pseudopapillary neoplasm

 Endocrine
Immunohistochemistry

 Infiltrating ductal adenocarcinoma

 Cytokeratin(CK): 7(+), 19(+), 20(-)
 CEA

 CA19-9

 Mucins
Risk factors of pancreatic cancer

 Advanced age
 Low socioeconomic status
 Cigarette
 Diabetes mellitus
 Chronic pancreatitis
 High-fat and cholesterol diet
 Carcinogens exposure
 PCBs, DDT, NNK, benzidine
Clinical presentation

 Abdominal pain
 Jaundice, obstructive
 Right-side dominant
 Weight loss, anorexia
 New-onset DM
 Acute pancreatitis
 Especially no risk factors, stones or alcohols
Clinical presentation

 Physical signs
 Jaundice: skin and sclera
 Hepatomegaly

 Palpable gall bladder

 Lymphadenopathy
 Left supraclavicle: Virchow’s node
 Periumbilical: Sister Mary Joseph’s node

 Peri-rectal region: Blumer’s shelf

Diagnosis

 Image studies
 CT or MRI: image of choice, equivalent
 ERCP: direct imaging of p-duct, replaced by
CT/MRI
 EUS: more accurate for tumor itself
 EUS-FNA
 PET: to be investigated
 Histopathologic diagnosis
Diagnosis

 Image studies
 Histopathologic diagnosis
 Direct operation: curative or palliative
 Percutaneous
 More complication: hemorrhage, pancreatitis,
fistula, abscess, tract seeding
 EUS-FNA
Staging

 T
 T1: limited to pancreas, <2cm
 T2: limited to pancreas, >2cm

 T3: extend beyond pancreas, not involve

celiac axis or SMA
 T4: involve celiac axis or SMA(unresectable)

 N
 N1: regional LN(+)
Staging

 IA: T1N0M0
 IB: T2N0M0
 IIA: T3N0M0
 IIB: T1N1M0, T2N1M0, T3N1M0
 III: T4, any N, M0
 IV: M1
Treatment – surgical resection

 Pancreatic head and neck

 Pancreaticoduodenectomy +/- distal
gastrectomy: Whipple’s operation
 Mortality: 2-3%
 Sepsis, hemorrhage , CV event
 Morbidity: 40-50%
 Leakage, abscess, delayed gastric emptying,
hemorrhage

 Pancreatic tail
Treatment – surgical resection

 Pancreatic head and neck

 Pancreatic tail
 No obstructive jaundice in early state
 Tend to be larger, usually metastasis at dx
 Distal pancreatectomy
Right-side versus Left-side pancreatic resection:
John Hopkins Experience (1984-1999)

Right-side Left-side
P value
(N=564) (N=52)
Tumor
3.1cm 4.7cm <0.01
diameter
Margin(+) 30% 20% NS
LN(+) 73% 59% 0.03
Post-op
2.3% 1.9% NS
mortality
Overall
31% 25% NS
complication
Post-op
11d 7d NS
hospital stay
Median
18m 12m NS
survival
For recurrence

 Disease nature
 Locally recurrence and distant mets
 Neoadjuvant/adjuvant treatment
 Chemoradiation
 5FU, MMC, Cisplatin, Paclitaxel, Gemcitabine
 Relative radioresistant

 Mostly single arm

 No definite evidence of survival benefit
Unresectable disease

 Palliative surgery
 RT or CCRT
 Radio-resistance
 5FU, Gemcitabine

 Really benefit?

 Palliative chemotherapy
Palliative surgery

 Obstructive jaundice
 Duodenal obstruction
 Hepaticojejunostomy
 Choledochoduodenostomy

 Cholecystojejunostomy

 Pain relief
 Neurolysis
Systemic chemotherapy

 Problems
 Highly resistant to chemotherapy
 Usually poor performance
 Pain, N/V, cachexia, weakness
 Impaired liver function
 Usually lack of measurable lesions
 Variation in phase II studies
Chemotherapy – historical

 5-FU is cornerstone
 Combination with
 Adramycin, mitomycin: FAM
 Cyc, MTX, Vincristine, Mitomycin

 Epirubicin, cisplatin, carboplatin, Ara-C

 High response rate in phase II : 40%

 Not confirmed in phase III
 Combination not better than 5FU alone
Gemcitabine

 Well-tolerated agent
 Phase III study, Gemzar vs. 5-FU
 Response rate: 5.4% vs. 0%
 Survival: 5.65m vs. 4.41m (p=0.0025)

 Clinical benefit: 23.8% vs. 4.8

 Pain, performance status, weight gain
 Toxicity similar with 5-FU
 Gemcitabine superior to 5-FU
Gemcitabine-based combination
Gemzar+Tarceva vs. Gemzar

ASCO annual meeting 2005, abstr no. 1

Biliary tract cancer
Classification

 Cholangiocarcinoma
 All tumors arise from bile duct epithelium
 Mostly adenocarcinoma
 Intrahepatic (6%)
 Hilum (67%): Klaskin’s tumor

 Distal extrahepatic (27%)

 Gall bladder
Epidemiology

 Old age: median 65 year-old

 Slightly more in men
 Uncommon cancer
 Uncertain nature course and treatment
Risk factors

 Chronic inflammation
 Primary sclerosing cholangitis : autoimmune
 Choledochal cyst : congenital

 Parasite

 Stone : maybe

 Repeat inflammation, stricture

 Young age-onset

 Carcinogens
Pathology

 Adenocarcinoma: 95%, most

 CK20(-), CK7(+)
 Squamous cell, small cell, sarcoma,
lymphoma

 CK20(-), CK7(+)
 CholangioCa, pancreatic Ca, lung adenoCa
 CK20(+), CK7(-)
 Colon cancer
Growth pattern

 Nodular type
 Intrahepatic
 Differential diagnosis of hepatic tumor
 HCC, cholangioCa, metastatic tumor
 Sclerosing type
 Hilum and distal
 Growth along the bile duct, difficult to
diagnosis
Clinical manifestation

 Painless jaundice
 Early in hilum/distal type
 Late in intrahepatic type
 Abnormal ALP/GGT
 Weight loss, nausea/vomit
 Palpable liver
 Intrahepatic type
 Biliary tract infection
 Due to obstruction
Clinical manifestation

 Tumor markers
 Elevated serum CEA and CA19-9
Diagnostic evaluation

 CT scan, ultrasound
 For painless jaundice, to exclude stone
 ERCP (Endoscopic Retrograde
CholangioPancreatography)
 Biliary tree evaluation
 Intervention: stenting, brushing cytology

 MRI/MRCP
 Non-invasive entire biliary tree evaluate
Extrahepatic Cholangiocarcinoma
T1 confined to the bile duct

T2 invades beyond the wall of the bile duct

T3 invades the liver, gallbladder, pancreas, and/or unilateral branches of the

portal vein or hepatic artery

T4 Invades any of the following: main portal vein or its branches bilaterally,
common hepatic artery, or other adjacent structures, such as the colon,
stomach, duodenum, or abdominal wall
N1 Regional lymph node metastasis

M1 Distant metastasis

Stage IA T1 N0 M0
Stage IB T2 N0 M0
Stage IIA T3 N0 M0

Stage IIB T1–T3 N1 M0

Stage III T4 Any N M0

Stage IV Any T Any N M1
Intrahepatic Cholangiocarcinoma
T1 Solitary tumor without vascular invasion
T2 Solitary tumor with vascular invasion or multiple tumors none >5 cm
T3 Multiple tumors >5 cm or tumor involving a major branch of the portal
or hepatic veins
T4 Tumor(s) with direct invasion of adjacent organs other than the
gallbladder or with perforation of visceral peritoneum
N1 Nodal metastases to the hepatoduodenal ligament
M1 Any distant metastases

Stage I T1 N0 M0
Stage II T2 N0 M0
Stage IIIA T3 N0 M0
Stage IIIB T4 N0 M0
Stage IIIC Any T N1 M0
Stage IV Any T Any N M1
Treatment

 Surgery: mainstay
 Biliary tree evaluation for resectability
 Intrahepatic: hepatic resection

 Extrahepatic: may require

pancreaticoduodenectomy, morbidity

 Prognosis: not clear, due to rarity

Multimodality treatment

 Pre-op neoadjuvant tx
 RT, C/T, CRT  no benefit
 Post-op adjuvant tx
 RT, C/T, CRT  no benefit
 A trial suggest adjuvant C/T may benefit GB ca
 Adjuvant CCRT for locally advance dz?
Locally advanced disease

 CCRT, can be considered

 5FU/LV
 Good performance

 Liver toxicity, GI toxicity

 Palliative chemotherapy
Palliative chemotherapy

 Pooled analysis, extra- and intra-hepatic

 5FU/LV remained mainstay
 Infusion, bolus
 RR: 20%-30%

 Survival 6-7m

 Combination:
 Traditional: cisplatin, mitomycin
 Newer agents: gemcitabine, taxane
Palliative procedure

 Biliary stenting, PTCD

 Complication of biliary stenting

 Communicate bile duct and intestine
 Bile is sterile

 Resultant repeat infection (BTI)