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!!!!

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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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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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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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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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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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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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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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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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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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Stage 4

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

SMA Margin

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

SMA Margin

SMV

SMA

SMV

SMA

Margin

Resectable Pancreas Cancer

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Unresectable – Locally Advanced Stage III

Pancreas Cancer

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

PANCAN.org

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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

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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

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Whipple Procedure

Distal Pancreatectomy

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Laparoscopic/Robotic Surgery

Incisions: Distal Pancreatectomy

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Vein Involvement

SMV

SMV

SMA

SMV/Portal Vein Resection

PV

IJ graft SMA

SMV

Pancreas

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How do we change the course?

• Prevention

• Early Detection

• Better Surgery

• Better Chemotherapy

• Novel techniques

The Gemcitabine Era

GemcitabineN=63

5-FUN=63

Median Survival 5.65mo 4.41mo

Survival 12mo 18% 2%

Burris, JCO, 1997.

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FOLFIRINOX for Metastatic Pancreatic Cancer

Overall Survival

FOLFIRINOX11.1 months

6.8 monthsGemcitabin

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.

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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

• No family history of cancer

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Celiac axis encased

Involvement of portal vein

• Laboratory work-up

– CA 19-9: 1213 U/ml

• EUS guided biopsy

– pancreatic adenocarcinoma

• EUS guided celiac ganglion block for pain control

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• Chemotherapy/radiation therapy first approach

– 10 cycles of FOLFIRINOX

– Radiation therapy

• Post-treatment

– CA 19-9 22U/ml

– CT scan with no metastases

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Superior mesenteric artery

Superior mesenteric vein

Celiac trunk

Tumor &

Margin of resection

Procedure

• Diagnostic laparoscopy

• Subtotal distal pancreatectomy with splenectomy

• Celiac artery axis and common hepatic artery resection

• Portal vein resection with primary repair

Pathology

• Complete pathologic response

– No viable cancer cells

• All Margins Negative

– pancreatic, celiac axis, common hepatic artery and portal vein

• All lymph nodes uninvolved with cancer

– 0 out of 12 lymph nodes positive

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How do we change the course?

• Prevention

• Early Detection

• Better Surgery

• Better Chemotherapy

• Novel techniques

Nanoknife

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We are changing the course!!

• Prevention– Tobacco cessation, weight control, diabetes control

• Early Detection– Working on it…

• Better Surgery– Complex resections

– Importance of going to a high volume center

• Better Chemotherapy– Use prior to surgery to convert unresectable to resectable disease

– Multidisciplinary tumor boards

• Novel techniques– Nanoknife