case presentation cc: jaundice hpi: 64-yr-old man 4 wk h/o anorexia & 15 lb wt loss 4 wk h/o...

CASE PRESENTATIONCASE PRESENTATION

CC:CC: JaundiceJaundice

HPI:HPI: 64-yr-old man64-yr-old man

• 4 wk h/o anorexia & 15 lb wt loss4 wk h/o anorexia & 15 lb wt loss

• 2 wk h/o2 wk h/o- prurituspruritus- dark urinedark urine- abdominal pain, midepigastric, dull, constant abdominal pain, midepigastric, dull, constant

with radiation to the backwith radiation to the back

• 2 days earlier a family members notes jaundice2 days earlier a family members notes jaundice

PMH:PMH: DM, type 2 (dx’d 6 yrs ago)DM, type 2 (dx’d 6 yrs ago)

PSH:PSH: NoneNone

Meds:Meds: glyburideglyburide

ALL:ALL: NKDANKDA

SH:SH: Married. No EtOH or tobaccoMarried. No EtOH or tobacco

FH:FH: No malignanciesNo malignancies

CASE PRESENTATIONCASE PRESENTATION

Physical ExamPhysical Exam

Vitals:Vitals: 120/83 65 12 AF 176 lbs120/83 65 12 AF 176 lbs

Gen:Gen: NAD.NAD.

Heent:Heent: Icteric. OP nl.Icteric. OP nl.

Neck:Neck: Supple. No LAD.Supple. No LAD.

Lungs:Lungs: CTA.CTA.

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

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

Ext:Ext: No c/c/e.No c/c/e.

CASE PRESENTATIONCASE PRESENTATION

CASE PRESENTATIONCASE PRESENTATION

Laboratory DataLaboratory Data

TBiliTBili 8.58.5

Alk phosAlk phos 350 350

ASTAST 7878

ALTALT 9090

AlbuminAlbumin 3.03.0

HgbHgb 10.510.5

PancreaticobiliaryPancreaticobiliaryCancerCancer

Rajeev Jain, M.D.Rajeev Jain, M.D.

2005 Estimated US Cancer Cases2005 Estimated US Cancer Cases

*Excludes basal and squamous cell skin cancers and in situ carcinomas except urinary bladder.Source: American Cancer Society, 2005.

Men710,040

Women662,870 32%32% BreastBreast

12%12% Lung and bronchusLung and bronchus

11%11% Colon and rectumColon and rectum

6%6% Uterine corpus Uterine corpus

4%4% Non-Hodgkin Non-Hodgkin lymphoma lymphoma

4%4% MelanomaMelanomaof skinof skin

3% Ovary3% Ovary

3%3% ThyroidThyroid

2%2% Urinary bladderUrinary bladder

2%2% PancreasPancreas

21%21% All Other SitesAll Other Sites

Prostate 33%

Lung and bronchus 13%

Colon and rectum 10%

Urinary bladder 7%

Melanoma of skin 5%

Non-Hodgkin4% lymphoma

Kidney 3%

Leukemia 3%

Oral Cavity 3%

Pancreas 2%

All Other Sites 17%

PancreasPancreas

•Acinar cells 80%

•Ductal cells 10-15%

•Endocrine cells 1-2%

Pancreatic CancerPancreatic Cancer

• EndocrineEndocrine- 1 to 2%1 to 2%

• ExocrineExocrine- > 95%> 95%- 85 to 90% ductal origin85 to 90% ductal origin

• HeadHead60-70%60-70%

• BodyBody 5-10% 5-10%• TailTail

10-15%10-15%

Pancreatic CancerPancreatic CancerWHO Classification - ExocrineWHO Classification - Exocrine

• MalignantMalignant- Ductal adenocarcinomaDuctal adenocarcinoma- Osteoclast-like giant cell tumorOsteoclast-like giant cell tumor- Serous cystadenocarcinomaSerous cystadenocarcinoma- Mucinous cystadenocarcinomaMucinous cystadenocarcinoma- Intraductal papillary mucinous carcinomaIntraductal papillary mucinous carcinoma- Acinar cell carcinomaAcinar cell carcinoma- PancreatoblastomaPancreatoblastoma- Solid-pseudopapillary carcinomaSolid-pseudopapillary carcinoma- Miscellaneous carcinomaMiscellaneous carcinoma

Pancreatic CancerPancreatic Cancer ACS 2005 EstimatesACS 2005 Estimates

32180 31800

0

10000

20000

30000

40000

2005

New Cases

Deaths

www.cancer.org

• Tobacco (RR 1.5 – 3)Tobacco (RR 1.5 – 3)

• Family history (7-10%)Family history (7-10%)- 1st degree relative: RR 3-51st degree relative: RR 3-5

• Familial syndromesFamilial syndromes- Hereditary pancreatitis (AD, cationic trypsinogen gene)Hereditary pancreatitis (AD, cationic trypsinogen gene)

• 40% by age 70, up to 75% if paternal40% by age 70, up to 75% if paternal- Peutz-JeghersPeutz-Jeghers- Von Hippel-LindauVon Hippel-Lindau- Familial atypical multiple-mole melanoma (FAMMM)Familial atypical multiple-mole melanoma (FAMMM)- Ataxia-telangiectasiaAtaxia-telangiectasia- FAP, HNPCCFAP, HNPCC

• Chronic pancreatitis (RR up to 16)Chronic pancreatitis (RR up to 16)

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

• Others: Obesity, inactivity, dietOthers: Obesity, inactivity, diet

Pancreatic CancerPancreatic CancerRisk Factors

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

Pancreatic CarcinogenesisPancreatic Carcinogenesis

•Activation of oncogenes

•Inactivation of tumor suppressor genes

•Defects in DNA mismatch repair genes

Pancreatic CancerPancreatic CancerPresentationPresentation

• Symptoms & signsSymptoms & signs- Jaundice, pruritus, acholic stoolJaundice, pruritus, acholic stool- Abdominal painAbdominal pain- Back painBack pain- Weight loss, anorexia, nausea & vomitingWeight loss, anorexia, nausea & vomiting- Curvoisier’s sign: palpable non-tender Curvoisier’s sign: palpable non-tender

gallbladdergallbladder

• Acute pancreatitisAcute pancreatitis

• New onset diabetesNew onset diabetes

• Pancreatic exocrine insufficiencyPancreatic exocrine insufficiency

Pancreatic CancerPancreatic CancerDiagnostic EvaluationDiagnostic Evaluation

• LaboratoryLaboratory- Tumor markersTumor markers

• RadiologyRadiology- Computed Tomography ScanComputed Tomography Scan- Magnetic Resonance Imaging (MRI/MRCP)Magnetic Resonance Imaging (MRI/MRCP)- Positron Emission TomographyPositron Emission Tomography- Percutaneous Transhepatic Cholangiography (PTC)Percutaneous Transhepatic Cholangiography (PTC)

• EndoscopyEndoscopy- Endoscopic Retrograde Cholangiopancreatography Endoscopic Retrograde Cholangiopancreatography

(ERCP)(ERCP)- Endoscopic Ultrasound (EUS)Endoscopic Ultrasound (EUS)

CA 19-9 Tumor-Associated AntigenCA 19-9 Tumor-Associated Antigen

• Synthesized by pancreatic and Synthesized by pancreatic and biliary ductal cellsbiliary ductal cells

• Lewis A blood groupLewis A blood group

• 5% of population is Lewis A-B- 5% of population is Lewis A-B- and cannot synthesize CA 19-and cannot synthesize CA 19-99

• Upper limit of normal 37 U/mlUpper limit of normal 37 U/ml- SensitivitySensitivity 81%81%- SpecificitySpecificity 90%90%

• False elevation: cholangitisFalse elevation: cholangitis

• CA 19-9 > 1000 predicts CA 19-9 > 1000 predicts unresectabilityunresectability

• Predicts recurrencePredicts recurrence

72

8792

97

0

20

40

60

80

100

37 100 300 1000

CA 19-9 Level, U/ml

PPV, %

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

Pancreatic CancerPancreatic CancerCT ScanCT Scan

Pancreas protocolPancreas protocol

• Thin cutsThin cuts

• PO/IV contrastPO/IV contrast

• First (pancreas) phaseFirst (pancreas) phase- 40s after IV contrast40s after IV contrast- Max. enhancement of Max. enhancement of

normal pancreasnormal pancreas

• Second (portal vein) phaseSecond (portal vein) phase- 70s after IV contrast70s after IV contrast- Liver metastasesLiver metastases- Tumor involvement of Tumor involvement of

portal & mesenteric veinsportal & mesenteric veins

Pancreatic CancerPancreatic CancerERCPERCP

• DiagnosticDiagnostic- Pancreatic ductal Pancreatic ductal

abnormalitiesabnormalities- Tissue (brushings)Tissue (brushings)

• Sens 18-60%, Spec 99%Sens 18-60%, Spec 99%

• TherapeuticTherapeutic- Biliary drainageBiliary drainage

• Plastic stentPlastic stent• Metal stentMetal stent

Pancreatic CancerPancreatic CancerERCPERCP

• Developed to overcome limitations of Developed to overcome limitations of transabdominal ultrasoundtransabdominal ultrasound- intervening structuresintervening structures- limited resolutionlimited resolution

• Transducer placed at distal end of Transducer placed at distal end of side-viewing endoscopeside-viewing endoscope

Endoscopic UltrasoundEndoscopic Ultrasound

Endoscopic UltrasoundEndoscopic Ultrasound

Radial Linear

360°100°

Pancreatic Mass with Pancreatic Mass with Vascular InvolvementVascular Involvement

Pancreatic CancerPancreatic CancerEndoscopic UltrasoundEndoscopic Ultrasound

• Tumor stagingTumor staging- more accurate than helical CT in small lesions more accurate than helical CT in small lesions

and assessing local extent, lymph nodes, & and assessing local extent, lymph nodes, & vascular invasionvascular invasion

- CT better for distant metastasesCT better for distant metastases- better than angiographybetter than angiography- ? MRI, MRCP, PET scan? MRI, MRCP, PET scan

• Diagnostic – Fine Needle Aspiration (FNA)Diagnostic – Fine Needle Aspiration (FNA)- SensitivitySensitivity 85%85%- SpecificitySpecificity 99%99%

Percutaneous Transhepatic Percutaneous Transhepatic Cholangiography (PTC)Cholangiography (PTC)

Pancreatic CancerPancreatic Cancer

SUSPICION OF PANCREATIC CANCER

Helical CT Scan

No tumor Pancreatic headtumor < 2 cm

ERCPEUS

Surgical exploration for resection

Tumor of body ortail of the pancreas

Laparoscopy withcytology of washings

Pancreatic headtumor > 2 cm

if +if -

PancreaticoduodenectomyPancreaticoduodenectomy

Pancreatic CancerPancreatic CancerPalliative IssuesPalliative Issues

• JaundiceJaundice- ERCP, PTC, or surgeryERCP, PTC, or surgery

• PainPain- Radiation therapyRadiation therapy- Celiac axis neurolysisCeliac axis neurolysis

• Surgical, fluoroscopic- or EUS-guidedSurgical, fluoroscopic- or EUS-guided

• Duodenal obstructionDuodenal obstruction- Surgery or metal stentSurgery or metal stent

Endoscopic StentsEndoscopic Stents

• Plastic stents: polyethylenePlastic stents: polyethylene- Drainage prior to surgeryDrainage prior to surgery- Up to 11.5 FrUp to 11.5 Fr- Life span < 3 monthsLife span < 3 months- $100$100

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

- PalliativePalliative- 10 mm or 30 Fr10 mm or 30 Fr- Longer patencyLonger patency- Life span > 3 monthsLife span > 3 months- $1,000$1,000

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

Pancreatic CancerPancreatic Cancer

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

Plastic v Metal Stent Plastic v Metal Stent Palliation of Biliary Obstruction in Palliation of Biliary Obstruction in

Pancreatic CancerPancreatic Cancer

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

Duodenal ObstructionDuodenal Obstruction

Duodenal ObstructionDuodenal Obstruction

Screening for Pancreatic CancerScreening for Pancreatic Cancer

• WhoWho- High-risk individualsHigh-risk individuals

• WhenWhen- Age 40 yrs or 10 yrs younger than the youngest Age 40 yrs or 10 yrs younger than the youngest

family member with PCfamily member with PC

• HowHow- Serology: Genetic and protein markersSerology: Genetic and protein markers- Radiology: CT, MRI/MRCPRadiology: CT, MRI/MRCP- Endoscopy: EUS, ERCPEndoscopy: EUS, ERCP

No guidelines or recommendationsStudies in progress – Univ. Washington & Johns Hopkins

Pancreatic CancerPancreatic Cancer AJCC StagingAJCC Staging

Primary Tumor (T)T1 Limited to pancreas, < 2 cmT2 Limited to pancreas, > 2 cmT3 Extension into duodenum, CBDT4 Extension into vessels (not splenic),

stomach, spleen, or colon

Regional Lymph Nodes (N)N0 NoneN1 Regional nodal metastases

Distant Metastases (M)M0 NoneM1 Distant metastases

Pancreatic CancerPancreatic Cancer AJCC StagingAJCC Staging

StageStage TT NN MM

II 11 00 00

22 00 00

IIII 33 00 00

11 11 00

IIIIII 22 11 00

33 11 00

IVAIVA 44 anyany 00

IVBIVB anyany anyany 11

Biliary Tract CancerBiliary Tract Cancer

• GallbladderGallbladder

• Extrahepatic bile ductExtrahepatic bile duct

• Ampulla of VaterAmpulla of Vater

Gallbladder CancerGallbladder Cancer• 2.5 cases per 100,0002.5 cases per 100,000

• 55thth most common GI cancer most common GI cancer

• 6,500 deaths/year6,500 deaths/year

• M:F 1:3M:F 1:3

• Risk factorsRisk factors- GallstonesGallstones- Porcelain gallbladderPorcelain gallbladder- Chronic typhoidal carrierChronic typhoidal carrier

• PresentationPresentation- Pain, jaundicePain, jaundice- 1-2% of resected 1-2% of resected

gallbladdersgallbladders

• 5 YR Survival: 5%5 YR Survival: 5%

Highest incidences (7-20/100,000)• Native Americans (North & South)• Poland• Northern India

CholangiocarcinomaCholangiocarcinoma

• 1 case per 100,0001 case per 100,000

• Slight M>FSlight M>F

• Risk factorsRisk factors- Primary sclerosing Primary sclerosing

cholangitis (PSC)cholangitis (PSC)- Choledochal cystsCholedochal cysts- Clonorchis sinensisClonorchis sinensis- HepatolithiasisHepatolithiasis- CBD stonesCBD stones- Thorium dioxide Thorium dioxide

(Thorotrast)(Thorotrast)

CholangiocarcinomaCholangiocarcinoma

• PresentationPresentation- Obstructive jaundiceObstructive jaundice

• DiagnosisDiagnosis- Tumor markersTumor markers

• CA 19-9 (85%)CA 19-9 (85%)• CEA (35%)CEA (35%)• CA 125 (30-50%)CA 125 (30-50%)

- ERCP/MRCPERCP/MRCP- CT scanCT scan

• TreatmentTreatment- SurgerySurgery

• PalliationPalliation- Biliary drainageBiliary drainage

• 5 YR Survival: 5%5 YR Survival: 5%

MRCP of PSC

ERCP

Bismuth ClassificationBismuth Classification

Ampullary CancerAmpullary Cancer

• 3 cases per 1 million3 cases per 1 million

• Risk factorsRisk factors- FAPFAP- Peutz-JeghersPeutz-Jeghers

• PresentationPresentation- JaundiceJaundice- ““Silver stool”Silver stool”

• Diagnosis/StagingDiagnosis/Staging- EGD, CT, EUS, ERCPEGD, CT, EUS, ERCP

• Treatment: SurgeryTreatment: Surgery

• 5 YR Survival: 25 – 40%5 YR Survival: 25 – 40%

Outcome of Patients after Outcome of Patients after PancreaticoduodenectomyPancreaticoduodenectomy

Operative Operative Mortality Mortality Rate (%)Rate (%)

Operative Operative Morbidity Morbidity Rate (%)Rate (%)

Median Median Survival Survival

(mos)(mos)

5-Year 5-Year Survival Survival Rate (%)Rate (%)

Pancreatic Pancreatic CancerCancer 3-153-15 27-4027-40 11-1811-18 6-266-26

Biliary Biliary Tract Tract

CancerCancer1-111-11 24-4424-44 22-3322-33 13-4313-43

Ampullary Ampullary CancerCancer 3-153-15 25-5925-59 38-4938-49 33-4833-48

Duodenal Duodenal CancerCancer 1-61-6 57-6457-64 8686 32-6032-60

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