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  • 5/19/2016

    1

    Understanding

    Pancreatic Cancer

    Advances in the

    Clinical Management of

    Pancreatic Cancer Nipun Merchant, MD

    Pancreas cancer….

    Don’t read the internet!!!!

  • 5/19/2016

    2

    The Pancreas

    Pancreas Function

    • Exocrine cells – Produce enzymes that

    help with digestion

    • Endocrine cells – Produce hormones that

    regulate blood sugar levels • Insulin -

    • Glucagon -

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    3

    Pancreatic Cancer

    • Pancreatic cancer begins when abnormal cells within the pancreas grow out of control and form a tumor

    • More than 95% of pancreatic cancers are exocrine tumors – Adenocarcinoma (PDAC)

    • Pancreatic neuroendocrine tumors (PNETs) account for less than 5% of all pancreatic tumors – Benign or malignant – Slow growing

    Risk Factors for PDAC

    • Risk factors that can be changed:

    – Tobacco use: • Risk 2x vs. those who have never smoked • 20% - 30% of all PDACs • Cigar and smokeless tobacco also risk factors

    – Overweight and obesity • Obese people – 20% more likely to develop PDAC

    – Workplace exposure to chemicals (?) • Dry-cleaning • Metal working industry

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    4

    Risk Factors for PDAC

    • Risk factors that cannot be changed:

    – Age – avg – 71 years

    – African American > White • ?smoking, diabetes, obesity

    – Family history: • Two or more first-degree relatives (sibling, parent) with

    pancreatic cancer

    • First-degree relative who developed pancreatic cancer before the age of 50

    • Inherited genetic syndromes associated with pancreatic cancer

    Inherited Genetic Syndromes

    • < 10% of PDACs: – Hereditary breast and ovarian cancer syndrome - BRCA1 or

    BRCA2 genes – Familial atypical multiple mole melanoma (FAMMM) syndrome -

    p16/CDKN2A gene – Familial pancreatitis -PRSS1 gene – Lynch syndrome (Hereditary non-polyposis colorectal cancer) -

    MLH1 or MSH2 genes – Peutz-Jeghers syndrome - STK11 gene – Von Hippel-Lindau syndrome - VHL gene

    • PNETs – Neurofibromatosis, type 1 - NF1 gene – Multiple endocrine neoplasia, type I (MEN1) - MEN1 gene

    • parathyroid gland, pituitary gland and PNETs

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    5

    Risk Factors for PDAC

    • Risk factors that cannot be changed:

    – Diabetes

    • Reason for this is not known

    • Most risk with type 2 diabetes – adult onset

    – ? related to being overweight or obese

    – Unclear if risk with with type 1 (juvenile) diabetes

    – Chronic pancreatitis

    • Long-term inflammation of the pancreas (especially in smokers)

    • Most people with pancreatitis never develop pancreatic cancer

    – Cirrhosis of the liver

    • Hepatitis and heavy alcohol use

    • Unclear risk:

    – Diet

    – Alcohol

    – Coffee +/-

    Complex Anatomy

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    6

    The Pancreas

    Head

    Body

    Tail

    Neck

    Pancreatic Cancer Symptoms: Location Matters

    • Initially silent and painless – By the time it causes symptoms, it has generally grown outside the

    pancreas

    • Symptoms depend on location:

    • Unexplained weight loss

    • Poor appetite

    • Jaundice • Dark urine, light color stool, itching

    • Nausea, vomiting

    • Abdominal pain

    • Back pain

    • Unexplained weight loss

    • Poor appetite

    • Abdominal pain

    • Back pain

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    7

    Diagnosis

    • ERCP

    • Endoscopic ultrasound (EUS)

    • CT scan

    • CA 19-9 blood test

    • CT/PET scan

    Endoscopic Retrograde Cholangiopancreatography (ERCP)

    • Biopsies, or samples of the tumor, can be obtained

    • Pictures taken show if the pancreatic or bile ducts are narrowed or blocked by a tumor

    • If bile duct is blocked a small plastic or metal stent, can be placed into a blocked bile duct to keep it open and allow bile to flow

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    8

    ERCP and Stent Placements

    EUS

    • Detailed ultrasound pictures of the pancreas, bile duct and digestive tract

    • Allows determination of: – Size and location of a tumor in the

    pancreas – Tumor spread to nearby lymph

    nodes – Invasion of nearby blood vessels

    • Biopsy - fine-needle aspiration (FNA)

    • Celiac ganglion block

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    9

    CT Imaging

    • CT scans are used to: – Detect the presence of a tumor

    – Determine the size and location of a tumor

    – Determine if the tumor has metastasized, or spread to other tissues

    – See the relationship of the tumor to surrounding blood vessels

    – Guide a biopsy

    – Help plan for surgery or radiation therapy

    – Determine whether the tumor is responding to treatment

    • “Pancreas Protocol CT”

    Combined Positron Emission Tomography (PET)/Computed Tomography (CT)

    • PET-CT scanning combines two imaging tests into one procedure

    • Images detect tissues that are using more glucose

    – Cancer cells use glucose at a faster rate than normal cells

    – Pancreatitis, infections, surgeries, and other diseases may change the way cells use glucose

    • Could produce false results on PET images

    • PET-CT is not a substitute for high-quality, contrast-enhanced CT scans

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    10

    CA 19-9

    • CA 19-9 (Lewis) antigens are foreign substances released by pancreatic tumor cells

    – Measured in blood

    • Elevated in many patients with pancreatic cancer

    • ≈ 15% do not secrete these antigens

    – Level normal even with PDAC

    • Many different conditions can cause elevation of CA 19-9

    – Other cancers

    – Jaundice

    – Pancreatitis

    – Cirrhosis

    • Cannot be used as a screening or diagnostic test for PDAC

    Stage 1

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    Stage 2

    Stage 3

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    12

    Stage 4

    Importance of Pre-operative Imaging: Focus on blood vessel margin

    SMA Margin

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    13

    Importance of Pre-operative Imaging: Focus on blood vessel margin

    SMA Margin

    SMV

    SMA

    SMV

    SMA

    Margin

    Resectable Pancreas Cancer

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    14

    Unresectable – Locally Advanced Stage III

    Pancreas Cancer

    Pancreatic Cancer Will be 2nd Most Common Cause of Death By Year 2020

    PANCAN.org

  • 5/19/2016

    15

    How do we change the course?

    • Prevention

    • Early Detection

    • Better Surgery

    • Better Chemotherapy

    • Novel techniques

    How do we change the course?

    • Prevention

    • Early Detection

    • Better Surgery

    • Better Chemotherapy

    • Novel techniques

  • 5/19/2016

    16

    Pancreas Cancer

     80% to 85% present with advanced disease

     10% confined to the pancreas

     40% local spread

     50% distant disease

     15% to 20% undergo potential curative resection

    How do we change the course?

    • Prevention

    • Early Detection

    • Better Surgery

    • Better Chemotherapy

    • Novel techniques

  • 5/19/2016

    17

    Whipple Procedure

    Distal Pancreatectomy

  • 5/19/2016

    18

    Laparoscopic/Robotic Surgery

    Incisions: Distal Pancreatectomy

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    19

    Vein Involvement

    SMV

    SMV

    SMA

    SMV/Portal Vein Resection

    PV

    IJ graft SMA

    SMV

    Pancreas

  • 5/19/2016

    20

    How do we change the course?

    • Prevention

    • Early Detection

    • Better Surgery

    • Better Chemotherapy

    • Novel techniques

    The Gemcitabine Era

    Gemcitabine N=63

    5-FU N=63

    Median Survival 5.65mo 4.41mo

    Survival 12mo 18% 2%

    Burris, JCO, 1997.

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    21

    FOLFIRINOX for Metastatic Pancreatic Cancer

    Overall Survival

    FOLFIRINOX 11.1 months

    6.8 months Gemcitabin

    e

    Conroy et al, NEJM, 2011.

    nab-Paclitaxel-Gemcitabine

    Hazard Ratio for Death (95% CI)

    0.72 (0.62-0.83)

    8.5 months

    6.7

    months

    Gemcitabi

    ne

    Overall Survival

    Survival(%)

    Months

    Abraxane + Gemcitabine for Metastatic Pancreatic Cancer

    Van Hoff et al, NEJM, 2013.

  • 5/19/2016

    22

    How do we change the course?

    • Prevention

    • Early Detection

    • Better Surgery

    • Better Chemotherapy

    • Novel techniques

    45 y/o man

    • History:

    – Presented with two week history of new onset back pain

    – No jaundice, no weight loss

    • Past Medical History:

    – Healthy, no previous surgeries