painless jaundice . . . painful diagnoses: radiologic ...painless jaundice . . . painful diagnoses:...

David M. DudzinskiGillian Lieberman, MD

Painless Jaundice . . . Painful Diagnoses:

Radiologic Evaluation of Periampullary Malignancies

David M. Dudzinski, Harvard Medical School Year IIIGillian Lieberman, MD

September 2004

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ED Presentation; BIDMC w/u85MMay 2004, presented to OSH ED s/p fall • Scleral icterus noted. • CT for workup of fall revealed pancreatic mass.

Referred to BIDMC• No abdominal pain or back pain. Jaundice over

past several days = “painless jaundice”– No pruritis, weight loss, or other GI symptoms

• Exam: “palpable, firm mass in the right upper quadrant, compatible with a Courvoisier’s gallbladder”

• Labs: indicative of obstructive jaundice– Bilirubin (total) 18.3 mg/dL (ref. 0-1.5 mg/dL)– Alkaline phosphatase 749 IU/L (ref. 39-117 IU/L)

PATIENT #1: FS

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CT Image: Pancreatic Mass

BIDMC PACS

IMV

06/02/04

Renal arteries

2 cm Pancreatic Head Mass

CBD Stent

SMA (shift left 2° to scoliosis)

IVC

PATIENT #1: FS

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Periampullary Anatomy

Netter FH. Atlas of Human Anatomy. 2d ed. 1997.

ANTERIOR VIEW POSTERIOR VIEW

Biliary Tree

SMA SMV

Celiac Axis Portal System

Hepatic Triad

Ampulla, CBD, PD

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Periampullary Mass LesionsDifferential diagnoses based on imaging • Malignant neoplasms• Focal pancreatitis• Benign neoplasms• Pancreas pseudocyst, traumatic cyst, necrosis• Abscess• Biloma, Hematoma• Lymphadenopathy• Aneurysm• Duodenal cyst, polyp, diverticulum

Overlap with DDx of obstructive jaundice ?

Reeder MM. Reeder and Felson’s Gamuts in Radiology. 4th ed. 2003.

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Painless JaundiceSign classically associated with malignant etiologies of extrahepatic or obstructive jaundice• Carcinoma of ampulla of Vater• Extrahepatic cholangiocarcinoma (“CCA”)• Ductal adenocarcinoma of the pancreatic head (“ACA”)

Diagnostic caveat• Painless jaundice in some cases of cholecystitis• Advanced malignancies may often present with pain

Painless jaundice is the most common presentation associated with a resectable and curable malignancy. • Thus, the radiologist can facilitate rapid, lifesaving

diagnosis and surgical intervention.

Kalser MH, et al. Cancer. 1985; 56:397-402.Molodell I, et al. Annals Oncol. 1999; 10:S82-S84.

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Menu of Radiologic ExamsUS: dilated ducts, r/o cholelithiasis / cholecystitis; not as likely to show tumorCT: masses, local anatomy, metastasesMRI/MRCP: biliary tree anatomyERCP: giving way to MRCP, therapeutic roleFuture Modalities (?)• EUS: (irregularly hypoechoic mass, pancreatic

duct dilatation)• Functional: (PET protocols to detect metastases)

Talamonti MS, Denham W. Radiol. Clin. N. Am. 2002; 40: 1397-410.

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CT ImagingHelical CT = primary imaging study in suspected periampullary malignancy• Detection: more sensitive than US ≈

90% vs. 75%

CT Findings• Focal mass, mass effects, distort gland contour• Hypoattenuation with IV contrast (hypovascularity)

– “Negative oral contrast”: duodenal-pancreatic interfaces• Smoothly dilated pancreatic duct, abrupt cut-off

– Double duct sign (CBD involvement)• Enlarged gallbladder

No masses, but dilatation ? MRI/MRCPFaria SC, et al. Semin. Roentgenol. 2004; 39: 397-411.

Horton KM, Fishman EK. Radiol. Clin. N. Am. 2002; 40: 1263-72.Nino-Murcia M, et al. Abd. Imaging. 2003; 28: 366-77.

Smith SL, Rajan PS. Clin. Radiol. 2004; 59: 26-38.

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MRI/MRCP StudiesMRI: (T1 fat suppressed) • Pancreatic ACA: low

signal on Gd contrast scan due to hypovascularity

• Cholangiocarcinoma: low T2 signal intensity due to desmoplastic character

MRCP: T2 (FSE) show fluid in biliary tree with high signal intensity• Double duct sign• PD: smooth or beaded vs.

irregular dilatation• CBD: irregular, ragged

strictures in CCA

Medical Center for Radiology, Philipps University at Marburg, http://online-media.uni-marburg.de/radiologie

CBD ≈

10 mm PD ≈

7 mm Malignant strictures

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Cancer of Ampulla of VaterPainless jaundice in 75%Intestinal histologyAssociated w/ FAPCBD/PD dilated to ampullaPatient JS:• 73F• Elevated

LFTs

Ampullary Mass

CBD Stent

BIDMC PACS06/25/04

PATIENT #2: JS

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Cancer of Ampulla of Vater (2)

Tend to present relatively earlyRetroperitoneal means less interference with other structuresBetter prognosis

BIDMC PACS

Ampullary Mass

CBD StentPancreatic Duct Dilatation 06/25/04

PATIENT #2: JS

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Extrahepatic Cholangiocarcinoma

Location in Biliary Tree• Perihilar (Klatskin tumor): 60-70%• Distal CBD: 20-30% • [Intrahepatic ducts 10%]

5 year survival ≈ 5-15%Semin. Liver Dis., July 2004: Clinical picture is “complex”, “not straightforward”, and “continues to defy diagnosis”.• Imaging complements clinical observations

to reach the diagnosis.

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CholangiocarcinomaPatient JC• 76M• Painless jaundice• Alk phos 389 IU/L• Bili 28.3 mg/dL

CT Findings• Asymmetric CBD wall

thickening, – With medial

enhancement near ampulla (fibrosis)

– CBD dilated near ampulla

• Hepatic artery proper• SMV, splenic veins

BIDMC PACS05/27/04

PATIENT #3: JC

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Cholangiocarcinoma (2)Patient MD: (Hosp. Univ. Pennsylvania)• 73F• Painless jaundice,

two weeks diarrhea• Alk phos 64 IU/L • Bili 7.7 mg/dL

MRCP Findings• 2.1 cm CBD stricture• Beaded left hepatic

duct Hospital of the University of Pennsylvania

06/02/0407/15Duodenal fluid

PATIENT #4: MD

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Pancreatic CancerEpidemiology (USA)• 31k new cases, 31k

deaths estimated in 2004

• 4th leading cause of cancer deaths for men and women

• 5 year survival < 5%Pathology• > 90% ductal

adenocarcinoma• 70% in pancreatic head • Broad DDx

St. George’s Hospital, Dept. of Histopathology http://www.sghms.ac.uk/depts/histopathology

PANCREATIC ADENOCARCINOMA IN HEAD OF PANCREAS

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Dilated Ducts in Pancreatic ACA

06/02/04 BIDMC PACS

RHD

CBD Panc.

Cystic

RECAP PATIENT #1: FS

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Role of Radiology in Treatment“Imaging studies play a critical role in evaluating patients with biliary obstruction, and because resection is the only effective treatment, such studies should be directed at fully assessing the extent of disease.”

Jarnagin WR, Shoup M. Semin. Liver Dis. 2004; 24: 189-99.

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Treatment OptionsPotentially curative for all three malignancies: Whipple Procedure• 80% inoperable

Palliative biliarytree stenting

(1) JHU Gastroenterology & Hepatology, http://hopkins-gi.nts.jhu.edu(2) BIDMC PACS

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CT Evaluation of ResectabilityPost processing methodologies / CT angio• Multiplanar 3D reconstruction• Curved planar reformation• 3D volume rendering• Maximum intensity projection (MIP)

Evaluate by CT:• Adjacent invasion of tumor• Vascular: hepatic phase acquisition

– Tumor encasement: vessel narrowing, deformation, obliteration, and collaterals

• Neurovascular plexus: check fat planes• Metastases and nodal Involvement

Nino-Murcia M, et al. Abd. Imaging. 2003; 28: 366-77.Prokesch RW, et al. Eur. Radiol. 2003; 13: 2147-54.

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Staging Pancreatic Cancer for Determining ResectabilityOncologic Staging: TMN• Size (< 2cm), extension, metastases, nodes

CTA Surgical Staging (Raptopoulos, 1997):• 0. Normal• 1. Smooth displacement of vessel, resectable• 2. Flattening or deforming a vessel, ? resectable• 3. Narrowed vein, unresectable (unclear margin)• 4. Occluded vessel, unresectable• (5. Distant Metastases, unresectable)

Identical concept for cholangiocarcinomaRaptopoulos V, et al. AJR 1997; 168:971-977.

Prokesch RW, et al. Eur. Radiol. 2003; 13: 2147-54.

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Clear Fat Planes

BIDMC PACS

Patient CK• 83M• Painless jaundice,

10 days duration• Bili 17.2 mg/dL• Alkphos 2024 IU/L

Clear Fat Planes• No interference

with vascular structures Aorta

(calcified)

SMVSMA

04/11/03

IVC3.2 cm Panc. Head Mass

Duodenum, Thick wall?

PATIENT #5: CK

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Clear Fat Planes (2)

BIDMC PACS

CT Recon Image• Surgical clips s/p

cholecystectomy• Ductal dilatation• Thin fat planes

between mass and– SMV– SMA

Predict Resectable• No interference

with vascular structures

• Category 1

04/11/03

PATIENT #5: CK

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SMV Involvement ?Patient BK• 65F• Jaundice, dark urine,

wt loss, pruritis 14d• Bili 13.1 mg/dL• Alk phos 471 IU/L

CT: “contiguous with SMV for 180°”, but• Predicted resectable• Category 2

Surgery:• “densely adherent . . .

not invaded . . . separated” from tumor

BIDMC PACS

SMVSMA

05/10/02

2.2 cm Panc. Head Mass

PATIENT #6: BK

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Portal Vein InvolvementPatient CJ• 53F• Jaundice, dark

urine, pruritis• Elevated LFTs

Unresectable• “Tear drop” sign

and thrombus in portal vein

• Category 3-4

BIDMC PACS

Distal SMA SMV

Splenic veinPortal vein

PATIENT #7: CJ

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Portal Vein Involvement (2)

06/10/04

BIDMC PACS

Common Hepatic a.

Diffuse Pancreatic Head Mass

Portal Vein, Thrombus, Tear Drop Sign

Fat Stranding ? Pancreatitis

Splenic a.

CBD Stent

PATIENT #7: CJ

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Venous Collateralization

BIDMC PACS

SMV and splenicvein tributaries to portal system blockedNote extensive collateral venous network • Peripancreatic• Lesser curvature• Greater curvature

PATIENT #7: CJ

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Metastases

BIDMC PACS

Patient PH• 72M• Jaundice, LLQ pain (?)• Bili 6.0, Alk phos 899

Thrombosed SMV

7x6 cm Mass

s/p R nephrectomy

IVC Compressed

Ascites: perisplenic, perihepatic. ? of peritoneal carcinomatosis

Metastases Pneumobilia

PATIENT #8: PH

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Patients’ ResultsPatient #1, FS: CT resectable, liver metastases at WhipplePatient #2, JS: CT resectable, s/p successful WhipplePatient #3, JC: CT resectable, awaiting Whipple, stent

placed by ERCPPatient #4, MD: MRI/MRCP resectable, s/p successful

WhipplePatient #5, CK: CT resectable, awaiting WhipplePatient #6, BK: CT resectable, s/p Whipple, but XRT/chemo for positive nodes diagnosed post surgeryPatient #7, CJ: CT non-resectable, chemotherapy/XRTPatient #8, PH: CT non-resectable, chemotherapy/stent

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Limitations: CT ResectabilityNPV of CT non-resectability approximately 100%In contrast, PPV of CT resectability lacking• 53% - 79% CT, 85+% with MDCT, CT angio

Causes of Lower PPV (false positives)• small (< 10mm) liver metastases (Patient #1, FS)• small peritoneal metastases• unknown nodal metastases (Patient #6, BK)• unappreciated portal vein or SMV involvement • unappreciated hepatic artery encasement • tumor spread: porta hepatis or root of mesentery• lack of CT angiography study

Lepanto L, et al. Radiology. 2002; 222:347-52.Raptopoulos V, et al. AJR 1997; 168:971-977.

Vargas R, et al. AJR 2004; 182:419-425.Valls C, et al. AJR 2002; 178: 821-826.

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SummaryPainless jaundice associated with curable periampullary malignancyRole of radiology in diagnosis• CT, MRI/MRCP methods distinguish

malignancies from other possible etiologiesRole of radiology in surgical planning• Involvement of adjacent vessels, tissues• Future improvements in CT detection and

staging of metastases, nodes

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ReferencesCay O, Raptopoulos V. Spiral CT for the Diagnosis and staging of pancreatic adenocarcinoma, in Spiral CT of the Abdomen (Terre F, Grossholz M, Becker CD, eds., 2002).Faria SC, Tamm EP, Loyer EM, Szklaruk J, Choi H, Charnsangavej C. Diagnosis and staging of pancreatic tumors. Semin. Roentgenol. 2004; 39: 397-411.Fletcher JG, Wiersema MJ, Farrell MA, et al. Pancreatic malignancy: value of arterial, pancreatic, and hepatic phase imaging with multi-detector row CT. Radiology 2003; 229: 81-90.Fujita N, Noda Y, Kobayashi G, Kimura K, Ito K. Endoscopic approach to early diagnosis of pancreatic cancer. Pancreas. 2004; 28: 279-81Horton KM, Fishman EK. Adenocarcinoma of the pancreas: CT imaging. Radiol. Clin. N. Am. 2002; 40: 1263-72.Kalra MK, Maher MM, Mueller PR, Saini S. State-of-the-art imaging of pancreatic neoplasms. Br. J. Radiol. 2003; 76: 857-65.Kalser MH, Barkin J, MacIntyre JM. Pancreatic cancer. Assessment of prognosis by clinical presentation. Cancer. 1985; 56:397-402.Lowenfels AB, Maisonneuve P. Epidemiology and prevention of pancreatic cancer. Jpn. J. Clin. Oncol. 2004; 34: 238-44.Nino-Murcia M, Jeffrey RB. Multidetector-row CT and volumetric imaging of pancreatic neoplasms. Gastroenterol. Clin. N. Am. 2002; 31: 881-96.Nino-Murcia M, Tamm EP, Charnsangavej C, Jeffrey RB. Multidetector-row helical CT and advanced postprocessing techniques for evaluation of pancreatic neoplasms. Abd. Imaging. 2003; 28: 366-77.Pafioleas MC, Moulakakis KG. Pancreatic cancer today. Hepato-gastroenterology. 2004; 51: 862-8.Prokesch RW, Schima W, Chow LC, Jeffrey RB. Multidetector CT of pancreatic adenocarcinoma: diagnostic advances and therapeutic relevance. Eur. Radiol. 2003; 13: 2147-54.

PANCREATIC CANCER

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Raptopoulos V, Steer ML, Sheiman RG, et al. The use of helical CT and CT angiography to predict vascular involvement from pancreatic cancer: correlation with findings at surgery. Am. J. Roentgenol. 1997; 168: 971-977. Smith SL, Rajan PS. Imaging of pancreatic adenocarcinoma with emphasis on multidetector CT. Clin. Radiol. 2004; 59: 26-38.Talamonti MS, Denham W. Staging and surgical management of pancreatic and biliary cancer and inflammation. Radiol. Clin. N. Am. 2002; 40: 1397-410.Valls C, Andia E, Sanchez A, et al. Dual-phase helical CT of pancreatic adenocarcinoma: assessment of resectability before surgery. Am. J. Roentgenol. 2002; 178: 821-826.Vargas R, Nino-Murcia M, Trueblood W, Jeffrey RB Jr. MDCT in Pancreatic adenocarcinoma: prediction of vascular invasion and resectability using a multiphasic technique with curved planar reformations. Am. J. Roentgenol. 2004; 182: 419-425.

References (cont.)

Abu-Hamda EM, Baron TH. Endoscopic management of cholangiocarcinoma. Semin. Liver Dis.2004; 24: 165-75.Chari RS, Love RC, Afdhal NH, Anderson C. Clinical manifestation and diagnosis of cholangiocarcinoma. UpToDate. 2004.Jarnagin WR, Shoup M. Surgical management of cholangiocarcinoma. Semin. Liver Dis. 2004; 24: 189-99. Lim JH. Cholangiocarcinoma: recent advances in imaging and intervention. Abd. Imaging. 2004; 29:538-9.Manfredi R, Barbaro B, Masselli G, Vecchioli A, Marano P. Magnetic resonance imaging of cholangiocarcinoma. Semin. Liver Dis. 2004; 24: 155-64.Olnes MJ, Erlich R. A review and update on cholangiocarcinoma. Oncology. 2004; 66: 167-79.

CHOLANGIOCARCINOMA

PANCREATIC CANCER

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References (cont.)AGA, AGA technical review: Epidemiology, diagnosis, and treatment of pancreatic ductaladenocarcinoma: Parts 1 and 2. UpToDate. 2004.BIDMC PACSChoi H, Loyer EM, Charnsangavej C. Neoplasms of the liver and bile ducts. Semin. Roentgenol.2004; 39: 312-427.Fayad LM, Kowalski T, Mitchell DG. MR cholangiopancreatography: evaluation of common pancreatic diseases. Radiol. Clin. N. Am. 2003; 41: 97-114.Fletcher ND, Wise PE, Sharp KW. Common bile duct papillary adenoma causing obstructive jaundice: case report and review of the literature. Am. Surg. 2004; 70: 448-52.Karnam US, Kruskal JB, Reddy KR. CT of the hepatobiliary tract. UpToDate. 2004.Lepanto L, Arzoumanian Y, Gianfelice D, et al. Helical CT with CT angiography in assessing periampullary neoplasms: identification of vascular invasion. Radiology. 2002; 222:347-52. Memon MA, Shiwani MH, Anwer S. Carcinoma of the ampulla of Vater: results of surgical treatment of a single center. Hepato-gastroenterology. 2004; 51:1275-7.Molodell I, Guarner L, Malageldala JR. Vagaries of clinical presentation of pancreatic and biliarytract cancer. Annals Oncol. 1999; 10:S82-S84.Motohara T, Semelka RC, Bader TR. MR cholangiopancreatography. Radiol. Clin. N. Am. 2003; 41: 89-96.National Cancer Institute. Pancreatic Cancer. http://www.nci.nih.gov/cancertopics/ Netter FH. Atlas of Human Anatomy. 2d ed. 1997.Parmar, MS. Courvoisier’s Law. Can. Med. Assoc. J. 2003; 168: 876.Reeder MM. Reeder and Felson’s Gamuts in Radiology. 4th ed. 2003.Rutstein L, Martin JA, Moser JA. Ampullary Carcinoma. UpToDate. 2004.

GENERAL

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Acknowledgements

Nicole Nelson, MD Jesse Wei, MDJason Handwerker, MDMichael Goldfinger, MDGillian Lieberman, MDPamela LepkowskiLarry Barbaras, our Webmaster

painless jaundice . . . painful diagnoses: radiologic ...painless jaundice . . . painful diagnoses:...

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