Radiologic and Anatomic Characterization of Pancreatic Cancer and

Frank Acosta, HMS IV

Gillian Lieberman, MD

Radiologic and Anatomic Characterization of Radiologic and Anatomic Characterization of Pancreatic Cancer and Implications for Pancreatic Cancer and Implications for

TreatmentTreatment

Frank L. Acosta, Jr., Harvard Medical School Year IVGillian Lieberman, MD

July 2001

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Agenda• Epidemiology• Classification• Relevant anatomy• Clinical presentation• Imaging studies• Management strategies • Salient points

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Epidemiology of Pancreatic CA

• Fifth leading cause of cancer-related death in U.S.• 29,000 new cases per year• Significant morbidity and mortality:

– 5 year survival rate: 2-5%– Median survival 15-20 months– Most patients have advanced disease at initial

presentation– Only 15-20% are surgical candidates

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Classification of Pancreatic NeoplasmsI. Epithelial nonendocrine tumors

A. Duct cell origin1. Cystic

a. Microcystic (serous) adenomab. Mucinous cystic neoplasm

(cystadenocarcinoma)c. Ductectatic neoplasms

2. Solida. Duct cell adenocarcinomab. Variant carcinomas

(1) Pleomorphic giant cell carcinoma(2) Adenosquamous carcinoma(3) Mucinous (colloid) carcinoma(4) Anaplastic carcinoma(5) Small cell carcinoma(6) Ciliated cell adenocarcinoma(7) Oncocytic carcinoma(8) Clear cell carcinoma

B. Acinar cell origin1. Acinar cell carcinoma2. Acinar cell cystadenocarcinoma3. Pancreaticoblastoma

C. Indeterminate origin1. Osteoclast-type giant cell carcinoma2. Solid and papillary epithelial neoplasm3. Mixed endocrine-exocrine tumors4. Microadenocarcinoma

II. Endocrine (islet cell) tumorsA. InsulinomaB. GastrinomaC. GlucagonomaD. VIPomaE. SomatostatinomaF. Pancreatic polypeptidomaG. CarcinoidH. Miscellaneous

III. Other pancreatic neoplasmsA. Nonepithelial (mesenchymal) tumorsB. MetastasesC. Lymphoma

Friedman AC: Pancreatic Neoplasms. In Friedman AC, Dachman AH, eds: Radiology of the liver, biliary tract, pancreas, and spleen, St. Louis, 1994, Mosby-Year Book, pp 807-934

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Classification of Pancreatic NeoplasmsI.I.I. Epithelial Epithelial Epithelial nonendocrinenonendocrinenonendocrine tumorstumorstumors

A.A.A. Duct cell originDuct cell originDuct cell origin1.1.1. CysticCysticCystic

a.a.a. MicrocysticMicrocysticMicrocystic (serous) adenoma(serous) adenoma(serous) adenomab.b.b. MucinousMucinousMucinous cystic neoplasm cystic neoplasm cystic neoplasm

(((cystadenocarcinomacystadenocarcinomacystadenocarcinoma)))c.c.c. DuctectaticDuctectaticDuctectatic neoplasmsneoplasmsneoplasms

2.2.2. SolidSolidSolida. DUCT CELL

ADENOCARCINOMA (90%)b.b.b. Variant carcinomasVariant carcinomasVariant carcinomas

(1)(1)(1) PleomorphicPleomorphicPleomorphic giant cell carcinomagiant cell carcinomagiant cell carcinoma(2)(2)(2) AdenosquamousAdenosquamousAdenosquamous carcinomacarcinomacarcinoma(3)(3)(3) MucinousMucinousMucinous (colloid) carcinoma(colloid) carcinoma(colloid) carcinoma(4)(4)(4) AnaplasticAnaplasticAnaplastic carcinomacarcinomacarcinoma(5)(5)(5) Small cell carcinomaSmall cell carcinomaSmall cell carcinoma(6)(6)(6) Ciliated cell Ciliated cell Ciliated cell adenocarcinomaadenocarcinomaadenocarcinoma(7)(7)(7) OncocyticOncocyticOncocytic carcinomacarcinomacarcinoma(8)(8)(8) Clear cell carcinomaClear cell carcinomaClear cell carcinoma

B.B.B. AcinarAcinarAcinar cell origincell origincell origin1.1.1. AcinarAcinarAcinar cell carcinomacell carcinomacell carcinoma2.2.2. AcinarAcinarAcinar cell cell cell cystadenocarcinomacystadenocarcinomacystadenocarcinoma3.3.3. PancreaticoblastomaPancreaticoblastomaPancreaticoblastoma

C.C.C. Indeterminate originIndeterminate originIndeterminate origin1.1.1. OsteoclastOsteoclastOsteoclast---type giant cell carcinomatype giant cell carcinomatype giant cell carcinoma2.2.2. Solid and papillary epithelial neoplasmSolid and papillary epithelial neoplasmSolid and papillary epithelial neoplasm3.3.3. Mixed endocrineMixed endocrineMixed endocrine---exocrine tumorsexocrine tumorsexocrine tumors4.4.4. MicroadenocarcinomaMicroadenocarcinomaMicroadenocarcinoma

II.II.II. Endocrine (islet cell) tumorsEndocrine (islet cell) tumorsEndocrine (islet cell) tumorsA.A.A. InsulinomaInsulinomaInsulinomaB.B.B. GastrinomaGastrinomaGastrinomaC.C.C. GlucagonomaGlucagonomaGlucagonomaD.D.D. VIPomaVIPomaVIPomaE.E.E. SomatostatinomaSomatostatinomaSomatostatinomaF.F.F. Pancreatic Pancreatic Pancreatic polypeptidomapolypeptidomapolypeptidomaG.G.G. CarcinoidCarcinoidCarcinoidH.H.H. MiscellaneousMiscellaneousMiscellaneous

III.III.III. Other pancreatic Other pancreatic Other pancreatic neoplasmsneoplasmsneoplasmsA.A.A. NonepithelialNonepithelialNonepithelial (((mesenchymalmesenchymalmesenchymal) tumors) tumors) tumorsB.B.B. MetastasesMetastasesMetastasesC.C.C. LymphomaLymphomaLymphoma

Friedman AC: Pancreatic Neoplasms. In Friedman AC, Dachman AH, eds: Radiology of the liver, biliary tract, pancreas, and spleen, St. Louis, 1994, Mosby-Year Book, pp 807-934

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Vascular Supply & Innervation

Netter FH. Atlas of Human Anatomy, New Jersey, 1989, Novartis.

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Pancreatic Duct

Gray H: Anatomy, Descriptive and Surgical. Pick TP, Howden R, eds. Philadelphia, 1974, Running Press.

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Establishing the Diagnosis• Initial presentation varies with the location of

tumor:– Head of pancreas Symptoms of obstruction of

the intrapancreatic portion of common bile duct (steatorrhea, weight loss, jaundice)

– Body, tail Symptoms from invasion of celiac ganglia (pain, weight loss). Obstruction less common

– Courvoisier’s law• Imaging studies play two primary roles:

– Diagnosis– Selecting optimal treatment strategies (i.e. surgical

vs. nonsurgical)

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Menu of tests for Imaging Pancreatic CA

Test Sensitivity Specificity Useful in StagingUS 80% 90% No

EUS 90% 90% YesCT 90% 95% Yes

ERCP 90% 90% NoMRI 90% 90% NoFNA 90% 98% No

Steer ML: Clinical manifestations and diagnosis of exocrine pancreatic cancer. From UpToDate literature search, http://www.uptodate.com

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Radiologic Studies in the Evaluation and Treatment of Suspected Pancreatic CA

Zeman RK, Silverman PM: Computed Tomography. In Evans SRT, Ascher SM, eds: Hepatobiliaryand Pancreatic Surgery: Imaging Strategies and Surgical Decision Making, New York, 1998, Wiley-Liss, pp 445-463.

Contrast-enhanced helical CT scan (or MRI)

Dilated biliary tree

Suspected pancreatic CA

Nondilated biliary tree

Unresectable on CT criteria

Unresectable FNA

ERCP (MRCP) +/- stent placement

Resectable based on CT criteria

Surgical exploration

Resectable

Questionable resectabilitybased on CT criteria

Visceral angiography or EUS

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J.C. E.G.• 74 yo female• 2 weeks intermittent

upper abdominal pain– “Achy” in nature– Radiating to back– Worse with eating– 5-10 lb weight loss

• PE no focal findings• Lab findings: wnl

• 70 yo male• Steatorrhea, weight loss• PE: Jaundice,

nontender palpable gallbladder

• Lab findings: Bili, Alk Phos

Let’s Discuss 2 Patients

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Radiologic Diagnosis - CT

• Patient J.C.• Diffuse enlargement• Focal low density

mass, noncalcified, at neck-body junction

• Dilated pancreatic duct

Image courtesy of BIDMC Department of Radiology

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DDX: Mass in the Region of the Pancreas on CT or MRI

• COMMON:– Pancreatic CA– Abscess (pancreas,

lesser sac)– Aortic aneurysm– CA of duodenum,

ampulla, bile duct, gallbladder, liver

– Gastric neoplasm– Lymphadenopathy– Metastasis– Pancreatic pseudocyst,

cyst, or benign neoplasm– Pancreatitits– Renal cyst or neoplasm– Splenic mass

• UNCOMMON:– Hydatid cyst– Portal vein

thromboembolism– Retroperitoneal cyst

or neoplasmReeder & Felson’s Gamuts in Radiology: Comprehensive List of Roentgen Differential Diagnoses.

Pathologic analysis is ‘gold standard’ for dx.

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Patient J.C.: Intact Mesenteric Artery- ResectableResectable

• CT revealed preservation of fat plane around SMA

• No evidence of metastatic disease


Hypodense fat plane surrounding SMA, indicating tumor has not invaded this vessel

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Surgical Treatment: Pancreaticoduodenectomy (Whipple)

http://pathology2.jhu.edu/pancreas/surgery.cfm

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Radiologic Diagnosis - CT

• Patient E.G.• Heterogeneous

mass in pancreatic head

• Dilated pancreatic and common bile ducts – “double duct” sign


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Patient E.G.: Involvement of Porto-Mesenteric Vasculature-Non Resectable

• CT-Angiogram (CTA) reconstruction demonstrated encased and compressed main portal vein at the origin of the superior mesenteric vein

• Not amenable to surgical resection


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Management Strategies

• Neoadjuvant chemotherapy • Surgical resection• Palliation• Depends on extent, location of tumor at

diagnosis•• Radiologic studies have a key role in Radiologic studies have a key role in

determining optimal treatment (i.e. determining optimal treatment (i.e. surgical vs. nonsurgical)surgical vs. nonsurgical)

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A different patient A showing Obliteration of Splenic Vein with Liver Metastases - Non Resectable


Obliterated splenic vein

Hepatic metastases

Siegelman ES: Pancreatic MR defines ducts, pinpoints disease. http://www.dimag.com/bodymri/pancreatic

• CT demonstrating: • MR max. intensity projection image (portal venousphase of contrast enhancement) showing:

Obliterated splenic vein (no contrast-asterix)Prominent collateral vessel (gastroepiploic vein)

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This patient may benefit from Palliation: Celiac Plexus Neurolysis (CPN)

• Chemical splanchnicectomy of celiac plexus (absolute ethanol)

• Ablates afferent nerve fibers that transmit visceral pain

• Approx. 70% will have relief of pain for up to 24 weeks

From Wiersema MJ, Wiersema LM. Endosonography-guided celiac plexus neurolysis. Gastrointest Endosc 1996; 44:656.

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Image-Guided Palliative Therapy

From Wiersema MJ, Wiersema LM. Endosonography-guided celiac plexus neurolysis. Gastrointest Endosc 1996; 44:656.

EUS Fluoroscopic monitoringEthanol distribution followinginjection into L periaortic space

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Lets review the appearance of Pancreatic Cancer on other

imaging modalities

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Patient B:Magnetic Resonance• MR imaging useful when clinical

suspicion for disease is high, but CT results are negative or equivocal

• T1-weighted fat-suppressed images usually provide better resolution– Desmoplastic reaction of

most pancreatic CA lowers signal intensity of tumor on T2-weighted images

– Better contrast between tumor and normal pancreas

Friedman AC: Pancreatic Neoplasms and Cysts. In Friedman AC, Dachman AH, eds: Radiology of the liver, biliary tract, pancreas, and spleen, St. Louis, 1994, Mosby-Year Book, pp 807-934.

T1-weighted image without fat-suppression shows poor contrast between tumor and normal pancreas

T1-weighted fat-suppressed image allows bettercontrast; normal pancreas (white arrow)increases in signal much more than tumor (blackarrow)

A

B

A

B

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ERCP & MRCP

Dilated, irregular pancreatic ductwith filling defects

Images courtesy of BIDMC Department of Radiology

ERCP: Patient C

Dilated side branches of pancreatic duct

MRCP: Patient D

Dilated pancreatic duct and side branches

Gallbladder

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Patient E: Endoscopic Ultrasound (EUS)• Improved diagnosis and

localization of small (<2- 3cm) lesions– Early identification is

crucial– 30% 5-year survival rate

• Useful in detecting lymph node and vascular involvement

• Can determine invasion of duodenal wall and pancreas by ampullary tumors

• More accurately detailed staging information

• Does not reliably detect lesions distant from the pancreas

http://www.mc.Vanderbilt.Edu/surgery/pncnprog.html

http://www.mgh.harvard.edu/endoscopy/Endo%20site/EUS.html

EUS of pancreatic massInvolving SMV-portal vein confluence

Diagram of echoendoscopeimaging pancreatic massthrough pyloric wall

http://www.mgh.harvard.edu/endoscopy/images/Panc mass.mov

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Patient F: The Preoperative Response to Treatment may be evaluated by Nuclear Medicine

• 18FDG-PET scan performed before (A) and after (B) taxol-based neoadjuvant chemoradiation.

URL: http://www.mc.Vanderbilt.Edu/surgery/pncnprog.html

Near total reduction in tumor-specific signal following completion of taxol-based neoadjuvant chemoradiation

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Take Home Points• Carcinoma of the pancreas is an almost uniformly

fatal cancer• Disturbances in pancreatic structure/function

determine initial presentation• Duct cell adenocarcinoma and its variants account for

~90% of all pancreatic tumors – most occur in the head of the pancreas

• CT is the best pancreatic imaging modality useful in detection and staging of pancreatic CA

• Helical CT and CTA are useful in determining vascular involvement, resectability of pancreatic tumors (10-15%):

• Radiologic techniques are essential in the performance of nonoperative palliation – CPN

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References• Friedman AC: Pancreatic Neoplasms and Cysts. In Friedman AC, Dachman AH, eds: Radiology of the

liver, biliary tract, pancreas, and spleen, St. Louis, 1994, Mosby-Year Book, pp 807-934.• Gray H: Anatomy, Descriptive and Surgical. Pick TP, Howden R, eds. Philadelphia, 1974, Running Press.• Kuroda A, Nagai H: Surgical Anatomy of the Pancreas. In Howard J, et al., eds: Surgical Diseases of the

Pancreas, Baltimore, 1998, Williams & Wilkins, pp 11-21.• Massachusetts General Hospital Endoscopy, http://mgh.harvard.edu/endoscopy.• Netter FH. Atlas of Human Anatomy, New Jersey, 1989, Novartis.• Novelline RA. Squire’s Fundamentals of Radiology, Cambridge, 1997, Harvard University Press.• Raptopoulos V, Steer ML, Sheiman RG, Vrachliotis TG, Gougoutas CA, Movson JS. The use of helical CT

and CT angiography to predict vascular involvement from pancreatic cancer: correlation with findings at surgery. AJR 1997; 168:971-977.

• Reeder & Felson’s Gamuts in Radiology: Comprehensive List of Roentgen Differential Diagnoses.• Siegelman ES: Pancreatic MR defines ducts, pinpoints disease.

http://www.dimag.com/bodymri/pancreatic.• Steer ML: Clinical manifestations and diagnosis of exocrine pancreatic cancer. From UpToDate literature

search, http://www.uptodate.com.• Thoeni RF, Blankenberg F: Pancreatic Imaging, Radiol Clin North Am 1993; 31:1085-1113.• Vanderbilt Department of Surgery, http://www.mc.Vanderbilt.Edu/surgery/pncnprog.• Wiersema MJ, Wiersema LM: Endosonography-guided celiac plexus neurolysis, Gastrointest Endosc

1996; 44:656• Zeman RK, Silverman PM: Computed Tomography. In Evans SRT, Ascher SM, eds: Hepatobiliary and

Pancreatic Surgery: Imaging Strategies and Surgical Decision Making, New York, 1998, Wiley-Liss, pp 445- 463.

http://mgh.harvard.edu/endoscopy

http://www.mc.vanderbilt.edu/surgery/pncnprog

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Acknowledgments

• Vassilios Raptopoulos, MD• Chad Brecher, MD• Gillian Lieberman, MD• Beverlee Turner & Pamela Lepkowski• Larry Barbaras and Cara Lyn D’amour,

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