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CASE PRESENTATION. CC: Jaundice HPI: 64-yr-old man 4 wk h/o anorexia & 15 lb wt loss 2 wk h/o pruritus dark urine abdominal pain, midepigastric, dull, constant with radiation to the back 2 days earlier a family members notes jaundice. CASE PRESENTATION.

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CASE PRESENTATION

CC: Jaundice

HPI: 64-yr-old man

  • 4 wk h/o anorexia & 15 lb wt loss

  • 2 wk h/o

    • pruritus

    • dark urine

    • abdominal pain, midepigastric, dull, constant with radiation to the back

  • 2 days earlier a family members notes jaundice


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CASE PRESENTATION

PMH: DM, type 2 (dx’d 6 yrs ago)

PSH: None

Meds: glyburide

ALL: NKDA

SH: Married. No EtOH or tobacco

FH: No malignancies


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CASE PRESENTATION

Physical Exam

Vitals: 120/83 65 12 AF 176 lbs

Gen: NAD.

Heent: Icteric. OP nl.

Neck: Supple. No LAD.

Lungs: CTA.

Heart: RRR w/o m/r/g.

Abd: NABS. Tender MEG. Palpable non- tender gallbladder.

Ext: No c/c/e.


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CASE PRESENTATION

Laboratory Data

TBili 8.5

Alk phos 350

AST 78

ALT 90

Albumin 3.0

Hgb 10.5


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Rajeev Jain, M.D.

PancreaticobiliaryCancer


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2005 Estimated US Cancer Cases

Men710,040

Women662,870

Prostate 33%

Lung and bronchus 13%

Colon and rectum 10%

Urinary bladder 7%

Melanoma of skin 5%

Non-Hodgkin 4% lymphoma

Kidney 3%

Leukemia 3%

Oral Cavity 3%

Pancreas 2%

All Other Sites 17%

32% Breast

12% Lung and bronchus

11% Colon and rectum

6% Uterine corpus

4% Non-Hodgkin lymphoma

4% Melanoma of skin

3% Ovary

3% Thyroid

2% Urinary bladder

2% Pancreas

21% All Other Sites

*Excludes basal and squamous cell skin cancers and in situ carcinomas except urinary bladder.

Source: American Cancer Society, 2005.


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Pancreas

  • Acinar cells 80%

  • Ductal cells 10-15%

  • Endocrine cells 1-2%


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Pancreatic Cancer

  • Endocrine

    • 1 to 2%

  • Exocrine

    • > 95%

    • 85 to 90% ductal origin

      • Head 60-70%

      • Body 5-10%

      • Tail 10-15%


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Pancreatic CancerWHO Classification - Exocrine

  • Malignant

    • Ductal adenocarcinoma

    • Osteoclast-like giant cell tumor

    • Serous cystadenocarcinoma

    • Mucinous cystadenocarcinoma

    • Intraductal papillary mucinous carcinoma

    • Acinar cell carcinoma

    • Pancreatoblastoma

    • Solid-pseudopapillary carcinoma

    • Miscellaneous carcinoma


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Pancreatic CancerACS 2005 Estimates

www.cancer.org


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Pancreatic CancerRisk Factors

  • Tobacco (RR 1.5 – 3)

  • Family history (7-10%)

    • 1st degree relative: RR 3-5

  • Familial syndromes

    • Hereditary pancreatitis (AD, cationic trypsinogen gene)

      • 40% by age 70, up to 75% if paternal

    • Peutz-Jeghers

    • Von Hippel-Lindau

    • Familial atypical multiple-mole melanoma (FAMMM)

    • Ataxia-telangiectasia

    • FAP, HNPCC

  • Chronic pancreatitis (RR up to 16)

  • Diabetes mellitus, type II (RR 2 if DM present > 5 yrs)

  • Others: Obesity, inactivity, diet

Michaud DS. Gastrointest Endosc 2002;56:S195-200.


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Pancreatic Carcinogenesis

  • Activation of oncogenes

  • Inactivation of tumor suppressor genes

  • Defects in DNA mismatch repair genes


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Pancreatic CancerPresentation

  • Symptoms & signs

    • Jaundice, pruritus, acholic stool

    • Abdominal pain

    • Back pain

    • Weight loss, anorexia, nausea & vomiting

    • Curvoisier’s sign: palpable non-tender gallbladder

  • Acute pancreatitis

  • New onset diabetes

  • Pancreatic exocrine insufficiency


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Pancreatic CancerDiagnostic Evaluation

  • Laboratory

    • Tumor markers

  • Radiology

    • Computed Tomography Scan

    • Magnetic Resonance Imaging (MRI/MRCP)

    • Positron Emission Tomography

    • Percutaneous Transhepatic Cholangiography (PTC)

  • Endoscopy

    • Endoscopic Retrograde Cholangiopancreatography (ERCP)

    • Endoscopic Ultrasound (EUS)


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CA 19-9 Tumor-Associated Antigen

  • Synthesized by pancreatic and biliary ductal cells

  • Lewis A blood group

  • 5% of population is Lewis A-B- and cannot synthesize CA 19-9

  • Upper limit of normal 37 U/ml

    • Sensitivity 81%

    • Specificity 90%

  • False elevation: cholangitis

  • CA 19-9 > 1000 predicts unresectability

  • Predicts recurrence

Steinberg W. Am J Gastroenterol 1990;85:350-5.


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Pancreatic CancerCT Scan

Pancreas protocol

  • Thin cuts

  • PO/IV contrast

  • First (pancreas) phase

    • 40s after IV contrast

    • Max. enhancement of normal pancreas

  • Second (portal vein) phase

    • 70s after IV contrast

    • Liver metastases

    • Tumor involvement of portal & mesenteric veins


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Pancreatic CancerERCP

  • Diagnostic

    • Pancreatic ductal abnormalities

    • Tissue (brushings)

      • Sens 18-60%, Spec 99%

  • Therapeutic

    • Biliary drainage

      • Plastic stent

      • Metal stent



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Endoscopic Ultrasound

  • Developed to overcome limitations of transabdominal ultrasound

    • intervening structures

    • limited resolution

  • Transducer placed at distal end of side-viewing endoscope


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Endoscopic Ultrasound

Radial

Linear

100°

360°


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Pancreatic Mass with Vascular Involvement


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Pancreatic CancerEndoscopic Ultrasound

  • Tumor staging

    • more accurate than helical CT in small lesions and assessing local extent, lymph nodes, & vascular invasion

    • CT better for distant metastases

    • better than angiography

    • ? MRI, MRCP, PET scan

  • Diagnostic – Fine Needle Aspiration (FNA)

    • Sensitivity 85%

    • Specificity 99%



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Pancreatic Cancer

SUSPICION OF PANCREATIC CANCER

Helical CT Scan

Pancreatic head

tumor < 2 cm

Pancreatic head

tumor > 2 cm

Tumor of body or

tail of the pancreas

No tumor

ERCP

EUS

Laparoscopy with

cytology of washings

if +

if -

Surgical exploration for resection



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Pancreatic CancerPalliative Issues

  • Jaundice

    • ERCP, PTC, or surgery

  • Pain

    • Radiation therapy

    • Celiac axis neurolysis

      • Surgical, fluoroscopic- or EUS-guided

  • Duodenal obstruction

    • Surgery or metal stent


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Endoscopic Stents

  • Plastic stents: polyethylene

    • Drainage prior to surgery

    • Up to 11.5 Fr

    • Life span < 3 months

    • $100

  • Metal stents: self-expanding metal stents (SEMS)

    • Palliative

    • 10 mm or 30 Fr

    • Longer patency

    • Life span > 3 months

    • $1,000


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ERCP Stent v Surgical Bypass Palliation of Biliary Obstruction in Pancreatic Cancer

Flamm CR et al. Gastrointest Endosc 2002;56(6):S218-25.


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Plastic v Metal Stent Palliation of Biliary Obstruction in Pancreatic Cancer

Levy MJ et al. Clin Gastroenterol Hepatol. 2004 Apr;2(4):273-85.




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Screening for Pancreatic Cancer

No guidelines or recommendations

Studies in progress – Univ. Washington & Johns Hopkins

  • Who

    • High-risk individuals

  • When

    • Age 40 yrs or 10 yrs younger than the youngest family member with PC

  • How

    • Serology: Genetic and protein markers

    • Radiology: CT, MRI/MRCP

    • Endoscopy: EUS, ERCP


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Pancreatic CancerAJCC Staging

Primary Tumor (T)

T1 Limited to pancreas, < 2 cm

T2 Limited to pancreas, > 2 cm

T3 Extension into duodenum, CBD

T4 Extension into vessels (not splenic),

stomach, spleen, or colon

Regional Lymph Nodes (N)

N0 None

N1 Regional nodal metastases

Distant Metastases (M)

M0 None

M1 Distant metastases


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Pancreatic CancerAJCC Staging


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Biliary Tract Cancer

  • Gallbladder

  • Extrahepatic bile duct

  • Ampulla of Vater


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Gallbladder Cancer

  • 2.5 cases per 100,000

  • 5th most common GI cancer

  • 6,500 deaths/year

  • M:F 1:3

  • Risk factors

    • Gallstones

    • Porcelain gallbladder

    • Chronic typhoidal carrier

  • Presentation

    • Pain, jaundice

    • 1-2% of resected gallbladders

  • 5 YR Survival: 5%

  • Highest incidences (7-20/100,000)

  • Native Americans (North & South)

  • Poland

  • Northern India


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Cholangiocarcinoma

  • 1 case per 100,000

  • Slight M>F

  • Risk factors

    • Primary sclerosing cholangitis (PSC)

    • Choledochal cysts

    • Clonorchis sinensis

    • Hepatolithiasis

    • CBD stones

    • Thorium dioxide (Thorotrast)


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Cholangiocarcinoma

MRCP of PSC

  • Presentation

    • Obstructive jaundice

  • Diagnosis

    • Tumor markers

      • CA 19-9 (85%)

      • CEA (35%)

      • CA 125 (30-50%)

    • ERCP/MRCP

    • CT scan

  • Treatment

    • Surgery

  • Palliation

    • Biliary drainage

  • 5 YR Survival: 5%

ERCP



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Ampullary Cancer

  • 3 cases per 1 million

  • Risk factors

    • FAP

    • Peutz-Jeghers

  • Presentation

    • Jaundice

    • “Silver stool”

  • Diagnosis/Staging

    • EGD, CT, EUS, ERCP

  • Treatment: Surgery

  • 5 YR Survival: 25 – 40%


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Outcome of Patients after Pancreaticoduodenectomy

Sarmiento JM, et al. Surg Clin North Am 2001.