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)