pancreatic biliary cancer by dr mahipal reddy
TRANSCRIPT
DR MAHIPAL REDDYINDUR ENDOSCOPY CENTRE
NIZAMBAD INDIA
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
SolidCystic
Mucinous cystic neoplasm Intraductal papillary mucinous neoplasm Serous cystic neoplasm Solid pseudopapillary neoplasm
Endocrine
Immunohistochemistry Infiltrating ductal adenocarcinoma
Cytokeratin(CK): 7(+), 19(+), 20(-)CEACA19-9Mucins
Risk factors of pancreatic cancerAdvanced ageLow socioeconomic statusCigarette Diabetes mellitusChronic pancreatitisHigh-fat and cholesterol dietCarcinogens exposure
PCBs, DDT, NNK, benzidine
Clinical presentationAbdominal painJaundice, obstructive
Right-side dominantWeight loss, anorexiaNew-onset DMAcute pancreatitis
Especially no risk factors, stones or alcohols
Clinical presentationPhysical signs
Jaundice: skin and scleraHepatomegalyPalpable gall bladderLymphadenopathy
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/MRIEUS: more accurate for tumor itself
EUS-FNAPET: to be investigated
Histopathologic diagnosis
Diagnosis Image studiesHistopathologic diagnosis
Direct operation: curative or palliative Percutaneous
More complication: hemorrhage, pancreatitis, fistula, abscess, tract seeding
EUS-FNA
Staging T
T1: limited to pancreas, <2cmT2: limited to pancreas, >2cmT3: extend beyond pancreas, not involve celiac
axis or SMAT4: involve celiac axis or SMA(unresectable)
NN1: regional LN(+)
StagingIA: T1N0M0IB: T2N0M0IIA: T3N0M0IIB: T1N1M0, T2N1M0, T3N1M0III: T4, any N, M0IV: M1
Treatment – surgical resectionPancreatic 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 resectionPancreatic head and neckPancreatic tail
No obstructive jaundice in early state Tend to be larger, usually metastasis at dx
Distal pancreatectomy
Right-side (N=564)
Left-side (N=52)
P value
Tumor diameter
3.1cm 4.7cm <0.01
Margin(+) 30% 20% NS
LN(+) 73% 59% 0.03
Post-op mortality
2.3% 1.9% NS
Overall complication
31% 25% NS
Post-op hospital stay
11d 7d NS
Median survival
18m 12m NS
Right-side versus Left-side pancreatic resection: John Hopkins Experience (1984-1999)
For recurrenceDisease nature
Locally recurrence and distant metsNeoadjuvant/adjuvant treatment
Chemoradiation 5FU, MMC, Cisplatin, Paclitaxel, Gemcitabine Relative radioresistant
Mostly single armNo definite evidence of survival benefit
Unresectable diseasePalliative surgeryRT or CCRT
Radio-resistance 5FU, GemcitabineReally benefit?
Palliative chemotherapy
Palliative surgeryObstructive jaundiceDuodenal obstruction
HepaticojejunostomyCholedochoduodenostomy Cholecystojejunostomy
Pain reliefNeurolysis
Systemic chemotherapy Problems
Highly resistant to chemotherapyUsually poor performance
Pain, N/V, cachexia, weaknessImpaired liver functionUsually 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 agentPhase 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 gainToxicity similar with 5-FU
Gemcitabine superior to 5-FU
Gemcitabine-based combination
Gemzar+Tarceva vs. Gemzar
ASCO annual meeting 2005, abstr no. 1
Classification Cholangiocarcinoma
All tumors arise from bile duct epithelium Mostly adenocarcinoma
Intrahepatic (6%)Hilum (67%): Klaskin’s tumorDistal extrahepatic (27%)Gall bladder
Epidemiology Old age: median 65 year-oldSlightly more in menUncommon cancerUncertain nature course and treatment
Risk factorsChronic inflammation
Primary sclerosing cholangitis : autoimmuneCholedochal cyst : congenitalParasite Stone : maybe Repeat inflammation, strictureYoung 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 patternNodular 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 typeLate in intrahepatic type
Abnormal ALP/GGTWeight loss, nausea/vomitPalpable liver
Intrahepatic typeBiliary tract infection
Due to obstruction
Clinical manifestationTumor markers
Elevated serum CEA and CA19-9
Diagnostic evaluation CT scan, ultrasound
For painless jaundice, to exclude stoneERCP (Endoscopic Retrograde
CholangioPancreatography)Biliary tree evaluationIntervention: stenting, brushing cytology
MRI/MRCPNon-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 CholangiocarcinomaT1 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 resectabilityIntrahepatic: hepatic resectionExtrahepatic: may require
pancreaticoduodenectomy, morbidity
Prognosis: not clear, due to rarity
Multimodality treatment Pre-op neoadjuvant tx
RT, C/T, CRT no benefitPost-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 diseaseCCRT, can be considered
5FU/LVGood performanceLiver toxicity, GI toxicity
Palliative chemotherapy
Palliative chemotherapyPooled analysis, extra- and intra-hepatic5FU/LV remained mainstay
Infusion, bolusRR: 20%-30%Survival 6-7m
Combination:Traditional: cisplatin, mitomycinNewer agents: gemcitabine, taxane
Palliative procedureBiliary stenting, PTCD
Complication of biliary stentingCommunicate bile duct and intestineBile is sterileResultant repeat infection (BTI)