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Pancreatic cancer

Pancreatic cancer. 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

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Pancreatic cancer

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  1. Pancreatic cancer

  2. Pathology • Exocrine • Solid • Infiltrating ductal adenocarcioma: most • Variant of ductal adenocarcinoma • Signet-ring cell, medullary, adenosquamous, anaplastic • Acinar cell carcinoma • Pancreatoblastoma • Cystic • Endocrine

  3. Pathology • Exocrine • Solid • Cystic • Mucinous cystic neoplasm • Intraductal papillary mucinous neoplasm • Serous cystic neoplasm • Solid pseudopapillary neoplasm • Endocrine

  4. Immunohistochemistry • Infiltrating ductal adenocarcinoma • Cytokeratin(CK): 7(+), 19(+), 20(-) • CEA • CA19-9 • Mucins

  5. 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

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

  7. 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

  8. 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

  9. Diagnosis • Image studies • Histopathologic diagnosis • Direct operation: curative or palliative • Percutaneous • More complication: hemorrhage, pancreatitis, fistula, abscess, tract seeding • EUS-FNA

  10. 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(+)

  11. Staging • IA: T1N0M0 • IB: T2N0M0 • IIA: T3N0M0 • IIB: T1N1M0, T2N1M0, T3N1M0 • III: T4, any N, M0 • IV: M1

  12. 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

  13. 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

  14. Right-side versus Left-side pancreatic resection: John Hopkins Experience (1984-1999)

  15. 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

  16. Unresectable disease • Palliative surgery • RT or CCRT • Radio-resistance • 5FU, Gemcitabine • Really benefit? • Palliative chemotherapy

  17. Palliative surgery • Obstructive jaundice • Duodenal obstruction • Hepaticojejunostomy • Choledochoduodenostomy • Cholecystojejunostomy • Pain relief • Neurolysis

  18. 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

  19. 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

  20. 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

  21. Gemcitabine-based combination

  22. Gemzar+Tarceva vs. Gemzar ASCO annual meeting 2005, abstr no. 1

  23. Biliary tract cancer

  24. Classification • Cholangiocarcinoma • All tumors arise from bile duct epithelium • Mostly adenocarcinoma • Intrahepatic (6%) • Hilum (67%): Klaskin’s tumor • Distal extrahepatic (27%) • Gall bladder

  25. Epidemiology • Old age: median 65 year-old • Slightly more in men • Uncommon cancer • Uncertain nature course and treatment

  26. Risk factors • Chronic inflammation • Primary sclerosing cholangitis : autoimmune • Choledochal cyst : congenital • Parasite • Stone : maybe • Repeat inflammation, stricture • Young age-onset • Carcinogens

  27. Pathology • Adenocarcinoma: 95%, most • CK20(-), CK7(+) • Squamous cell, small cell, sarcoma, lymphoma • CK20(-), CK7(+) • CholangioCa, pancreatic Ca, lung adenoCa • CK20(+), CK7(-) • Colon cancer

  28. 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

  29. 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

  30. Clinical manifestation • Tumor markers • Elevated serum CEA and CA19-9

  31. 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

  32. Treatment • Surgery: mainstay • Biliary tree evaluation for resectability • Intrahepatic: hepatic resection • Extrahepatic: may require pancreaticoduodenectomy, morbidity • Prognosis: not clear, due to rarity

  33. 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?

  34. Locally advanced disease • CCRT, can be considered • 5FU/LV • Good performance • Liver toxicity, GI toxicity • Palliative chemotherapy

  35. 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

  36. Palliative procedure • Biliary stenting, PTCD • Complication of biliary stenting • Communicate bile duct and intestine • Bile is sterile • Resultant repeat infection (BTI)

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