CASE PRESENTATION CC Jaundice HPI 64 yrold man

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CASE PRESENTATION CC: Jaundice HPI: 64 -yr-old man • • 4 wk h/o anorexia

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

CASE PRESENTATION PMH: DM, type 2 (dx’d 6 yrs ago) PSH: None Meds: glyburide

CASE PRESENTATION PMH: DM, type 2 (dx’d 6 yrs ago) PSH: None Meds: glyburide ALL: NKDA SH: Married. No Et. OH or tobacco FH: No malignancies

CASE PRESENTATION Physical Exam Vitals: 120/83 65 12 AF 176 lbs Gen: NAD. Heent:

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 nontender gallbladder. Ext: No c/c/e.

CASE PRESENTATION Laboratory Data TBili 8. 5 Alk phos 350 AST 78 ALT 90

CASE PRESENTATION Laboratory Data TBili 8. 5 Alk phos 350 AST 78 ALT 90 Albumin Hgb 10. 5 3. 0

Pancreaticobiliary Cancer Rajeev Jain, M. D.

Pancreaticobiliary Cancer Rajeev Jain, M. D.

2005 Estimated US Cancer Cases Prostate Men 710, 040 Women 662, 870 32% Breast

2005 Estimated US Cancer Cases Prostate Men 710, 040 Women 662, 870 32% Breast Lung and bronchus 13% 12% Lung and bronchus Colon and rectum 10% 11% Colon and rectum Urinary bladder 7% 6% Uterine corpus Melanoma of skin 5% 4% Non-Hodgkin lymphoma 4% Kidney 3% Melanoma of skin Leukemia 3% 3% Ovary Oral Cavity 3% 3% Thyroid Pancreas 2% 2% Urinary bladder 2% Pancreas All Other Sites 33% 17% 21% All Other Sites *Excludes basal and squamous cell skin cancers and in situ carcinomas except urinary bladder. Source: American Cancer Society, 2005.

Pancreas • Acinar cells 80% • Ductal cells 10 -15% • Endocrine cells 1

Pancreas • Acinar cells 80% • Ductal cells 10 -15% • Endocrine cells 1 -2%

Pancreatic Cancer • Endocrine - 1 to 2% • Exocrine - > 95% -

Pancreatic Cancer • Endocrine - 1 to 2% • Exocrine - > 95% - 85 to 90% ductal origin • Head 60 -70% • Body 5 -10% • Tail 10 -15%

Pancreatic Cancer WHO Classification - Exocrine • Malignant - Ductal adenocarcinoma Osteoclast-like giant cell

Pancreatic Cancer WHO 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

Pancreatic Cancer ACS 2005 Estimates www. cancer. org

Pancreatic Cancer ACS 2005 Estimates www. cancer. org

Pancreatic Cancer Risk Factors • • Tobacco (RR 1. 5 – 3) • Familial

Pancreatic Cancer Risk Factors • • Tobacco (RR 1. 5 – 3) • 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) Family history (7 -10%) - 1 st degree relative: RR 3 -5 Diabetes mellitus, type II (RR 2 if DM present > 5 yrs) Others: Obesity, inactivity, diet Michaud DS. Gastrointest Endosc 2002; 56: S 195 -200.

Pancreatic Carcinogenesis • Activation of oncogenes • Inactivation of tumor suppressor genes • Defects

Pancreatic Carcinogenesis • Activation of oncogenes • Inactivation of tumor suppressor genes • Defects in DNA mismatch repair genes

Pancreatic Cancer Presentation • Symptoms & signs - Jaundice, pruritus, acholic stool Abdominal pain

Pancreatic Cancer Presentation • 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

Pancreatic Cancer Diagnostic Evaluation • Laboratory - Tumor markers • Radiology - Computed Tomography

Pancreatic Cancer Diagnostic 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)

CA 19 -9 Tumor-Associated Antigen • Synthesized by pancreatic and biliary ductal cells •

CA 19 -9 Tumor-Associated Antigen • Synthesized by pancreatic and biliary ductal cells • • Lewis A blood group • Upper limit of normal 37 U/ml - Sensitivity 81% - Specificity 90% • • False elevation: cholangitis • Predicts recurrence 5% of population is Lewis A-Band cannot synthesize CA 19 -9 > 1000 predicts unresectability Steinberg W. Am J Gastroenterol 1990; 85: 350 -5.

Pancreatic Cancer CT Scan Pancreas protocol • • • Thin cuts • Second (portal

Pancreatic Cancer CT Scan Pancreas protocol • • • Thin cuts • Second (portal vein) phase - 70 s after IV contrast - Liver metastases - Tumor involvement of portal & mesenteric veins PO/IV contrast First (pancreas) phase - 40 s after IV contrast - Max. enhancement of normal pancreas

Pancreatic Cancer ERCP • Diagnostic - Pancreatic ductal abnormalities - Tissue (brushings) • Sens

Pancreatic Cancer ERCP • Diagnostic - Pancreatic ductal abnormalities - Tissue (brushings) • Sens 18 -60%, Spec 99% • Therapeutic - Biliary drainage • Plastic stent • Metal stent

Pancreatic Cancer ERCP

Pancreatic Cancer ERCP

Endoscopic Ultrasound • Developed to overcome limitations of transabdominal ultrasound - intervening structures -

Endoscopic Ultrasound • Developed to overcome limitations of transabdominal ultrasound - intervening structures - limited resolution • Transducer placed at distal end of side-viewing endoscope

Endoscopic Ultrasound Radial Linear 100° 360°

Endoscopic Ultrasound Radial Linear 100° 360°

Pancreatic Mass with Vascular Involvement

Pancreatic Mass with Vascular Involvement

Pancreatic Cancer Endoscopic Ultrasound • Tumor staging - more accurate than helical CT in

Pancreatic Cancer Endoscopic 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%

Percutaneous Transhepatic Cholangiography (PTC)

Percutaneous Transhepatic Cholangiography (PTC)

Pancreatic Cancer SUSPICION OF PANCREATIC CANCER Helical CT Scan No tumor Pancreatic head tumor

Pancreatic Cancer SUSPICION OF PANCREATIC CANCER Helical CT Scan No tumor Pancreatic head tumor < 2 cm ERCP EUS Pancreatic head tumor > 2 cm Tumor of body or tail of the pancreas Laparoscopy with cytology of washings if + if - Surgical exploration for resection

Pancreaticoduodenectomy

Pancreaticoduodenectomy

Pancreatic Cancer Palliative Issues • Jaundice - ERCP, PTC, or surgery • Pain -

Pancreatic Cancer Palliative Issues • Jaundice - ERCP, PTC, or surgery • Pain - Radiation therapy - Celiac axis neurolysis • Surgical, fluoroscopic- or EUS-guided • Duodenal obstruction - Surgery or metal stent

Endoscopic Stents • Plastic stents: polyethylene - Drainage prior to surgery Up to 11.

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

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

ERCP Stent v Surgical Bypass Palliation of Biliary Obstruction in Pancreatic Cancer Flamm CR et al. Gastrointest Endosc 2002; 56(6): S 218 -25.

Plastic v Metal Stent Palliation of Biliary Obstruction in Pancreatic Cancer Levy MJ et

Plastic v Metal Stent Palliation of Biliary Obstruction in Pancreatic Cancer Levy MJ et al. Clin Gastroenterol Hepatol. 2004 Apr; 2(4): 273 -85.

Duodenal Obstruction

Duodenal Obstruction

Duodenal Obstruction

Duodenal Obstruction

Screening for Pancreatic Cancer No guidelines or recommendations Studies in progress – Univ. Washington

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

Pancreatic Cancer AJCC Staging Primary Tumor (T) T 1 T 2 T 3 T

Pancreatic Cancer AJCC Staging Primary Tumor (T) T 1 T 2 T 3 T 4 Limited to pancreas, < 2 cm Limited to pancreas, > 2 cm Extension into duodenum, CBD Extension into vessels (not splenic), stomach, spleen, or colon Regional Lymph Nodes (N) N 0 None N 1 Regional nodal metastases Distant Metastases (M) M 0 None M 1 Distant metastases

Pancreatic Cancer AJCC Staging Stage T N M I 1 0 0 2 0

Pancreatic Cancer AJCC Staging Stage T N M I 1 0 0 2 0 0 3 0 0 1 1 0 2 1 0 3 1 0 IVA 4 any 0 IVB any 1 II III

Biliary Tract Cancer • Gallbladder • Extrahepatic bile duct • Ampulla of Vater

Biliary Tract Cancer • Gallbladder • Extrahepatic bile duct • Ampulla of Vater

Gallbladder Cancer • • • 2. 5 cases per 100, 000 5 th most

Gallbladder Cancer • • • 2. 5 cases per 100, 000 5 th 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

Cholangiocarcinoma • 1 case per 100, 000 • Slight M>F • Risk factors -

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)

Cholangiocarcinoma • Presentation - Obstructive jaundice • Diagnosis - Tumor markers • CA 19

Cholangiocarcinoma • 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% MRCP of PSC ERCP

Bismuth Classification

Bismuth Classification

Ampullary Cancer • 3 cases per 1 million • Risk factors - FAP -

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%

Outcome of Patients after Pancreaticoduodenectomy Operative Mortality Rate (%) Operative Morbidity Rate (%) Median

Outcome of Patients after Pancreaticoduodenectomy Operative Mortality Rate (%) Operative Morbidity Rate (%) Median Survival (mos) 5 -Year Survival Rate (%) 3 -15 27 -40 11 -18 6 -26 1 -11 24 -44 22 -33 13 -43 Ampullary Cancer 3 -15 25 -59 38 -49 33 -48 Duodenal Cancer 1 -6 57 -64 86 32 -60 Pancreatic Cancer Biliary Tract Cancer Sarmiento JM, et al. Surg Clin North Am 2001.