Pancreatic  Biliary Cancer by Dr Mahipal reddy
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Pancreatic Biliary Cancer by Dr Mahipal reddy

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Pancreatic  Biliary Cancer by Dr Mahipal reddy Pancreatic Biliary Cancer by Dr Mahipal reddy Presentation Transcript

  • DR MAHIPAL REDDY INDUR 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
      • 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 (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
  • 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
  •  
  •  
  •  
  • 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)