Surgical Techniques & Interpretation

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Surgical Techniques & Interpretation

November 9, 2015

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Pancreatic Cancer: Surgical Techniques

Christopher L. Wolfgang, MD, PhD, FACS

Chief of Hepatobiliary and Pancreatic Surgery

Professor of Surgery, Pathology and Oncology

Paul K. Neumann Professor of Pancreatic Cancer Research

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How do we win the war?

Local Battle

Systemic Battle

Local Battle

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The Local Battle is Fought

with Surgery

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Systemic Battle

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The Systemic Battle is Fought

With Chemotherapy or

Biological Therapy

How do we determine what

therapy someone with

pancreatic cancer receives?

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Clinical StagingClinical StagingClinical StagingClinical Staging

Potentially ResectablePotentially ResectablePotentially ResectablePotentially Resectable

(20%)(20%)(20%)(20%)• Localized

• Borderline

(potentially curable)

Unresectable (80%)Unresectable (80%)Unresectable (80%)Unresectable (80%)

• Metastatic

• Locally Advanced

(unlikely to be cured)

1. Systemic Spread

2. Local Tumor Relationship

Determination of ResectabilityDetermination of ResectabilityDetermination of ResectabilityDetermination of Resectability

• Metastatic

– Liver

– Peritoneum

– Lung

– CT scan

– PET scan

– Laparoscopic

Exploration

• Local Tumor

Relationships

– Superior Mesenteric

Artery/Celiac Axis

– Portal Vein/Superior

Mesenteric Vein

– Adjacent Organs

– CT scan

– EUS

– Not Surgical Exploration

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Resectable Unresectable

Management

• Stage I/II (resectable)

– Surgery

– Adjuvant or Neoadjuvant Therapy

• Stage III (locally advanced, unresectable

and borderline resectable)

– Chemoradiotherapy for locally advanced

– Neoadjuvant for borderline

• Stage IV

– Systemic therapy

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Multidisciplinary Care: Especially Important for

Pancreatic Cancer

Biopsy Proven or Suspected Pancreatic Cancer

Staging Work-up: Genetics, Family Hx, Functional Status

Imaging: 3-D CT scan, MRI, Functional Imaging

Labs: CBC, Liver function, Ca 19-9

Borderline Resectable Unresectable

SurgeryNeoadj CRT

Metastatic or Unresectable

Chemotherapy CRT Chemo SBRT

or

3X10

Surgery

(IORT?)

ADJ Tx

Resectable

Pancreatic MDC: Case Review

Review Images

CT/PET/MRI/

EUS

Discuss Case

and reach

consensus

Review

Pathology

See patients and

discuss options

Present Cases

using outline

Enroll in trials/studies

Dictate note and cc to

referring physicians

• Oncology

• Radiation

Oncology

• Surgery

• Pathology

• Diagnostic

Imaging

• Pain Medicine

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Pancreaticoduodenectomy for Head and Uncinate Cancer

Distal Pancreatectomy for Body and Tail Cancer

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Atlas of Upper Gastrointestinal and HepatoAtlas of Upper Gastrointestinal and HepatoAtlas of Upper Gastrointestinal and HepatoAtlas of Upper Gastrointestinal and Hepato----PancreatoPancreatoPancreatoPancreato----Biliary Surgery (Douglas Evans)Biliary Surgery (Douglas Evans)Biliary Surgery (Douglas Evans)Biliary Surgery (Douglas Evans)


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Surgical Margins

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Minimally Invasive Whipple

Operation

(Robotic or Laparoscopic)

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Vessel Involvement

(Stage III)

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Resection determined by vessel

involvement

AHPBA/SSO/SSAT/NCCN

Resectable BorderlineLocally

Advanced

SMV/PV No contactAbut, encase or

occludeNot

reconstructable

SMA/Hepatic No contact Abut Encase

CHA No contactAbut or short-

segment encaseLong-segment

encase

Celiac Trunk No contact No contact Any contact

BorderlineLocally

advancedResectable

Sandone 5A

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Locally Advanced and

Unresectable

Sandone 2

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Sandone 6

MLC 406 US Rev B

How Electroporation Works

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NanoKnife® System

SMVSMASMV

SMA

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Preoperative CT

2/06

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Pancreatic Cancer is Almost

Always a Systemic Disease at

the Time of Diagnosis

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1980s (N=65) 1990s (N=512) 2000s (N=1115)

months 12 24 36 48 60 12 24 36 48 60 12 24 36 48 60

# at risk 42 23 16 12 10 355 189 139 108 96 740 414 232 162 110

Survival Of Pancreatic Cancer By Decade

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Personalized Approach

To Treatment

PalB2

• Partner and Localizer of BRCA2

• 3% of familial pancreatic cancer (also a

cause of familial breast cancer)

• Familial predisposition genes can be

discovered by sequencing all known

genes in a single patient!!

S. Jones, et al. Science 2009

EP Slater, et al. Clin Genet. 2010

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Biallelic PALB2 mutations in Pa10

Family History of Pancreatic, Breast and Ovarian Cancer

4CM, 8+LN, Margin +, Poorly Differentiated, Supraclavicular

metastasis at first post-op visit, Progressed on Gemcitabine,

Developed lung metastases

Villarroel

et al., Mol

Cancer

Ther.

2010

Biallelic PALB2 mutations in Pa10

Treated with Mitomycin C, Patient lived 5

years!

0

20000

40000

60000

80000

100000

120000

GemcitabineDiagnosis Mitomycin C

Villarroel

et al., Mol

Cancer

Ther.

2010

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Summary• There are 2 battles to fight to win the war on

pancreatic cancer

– Systemic and Local

• The treatment for pancreatic cancer is based on the

stage

• Surgery plays an important role in localized disease

• Whipple Operation – pancreatic head lesions

• Distal Pancreatectomy and Splenectomy for body

and tail lesions

• Most surgical failures are systemic

– Chemotherapy is used to combat this problem

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Interpretation

Martha Bishop Pitman, MD

Director of Cytology

Massachusetts General Hospital

Associate Professor of Pathology

Harvard Medical School

Patient Care Team

Microscope Clipart by ben : Science Cliparts #17424- ClipartSE

www.freepik.com

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Pathologist

• A medical doctor specialist in pathology;

specifically, a physician who interprets and

diagnoses the changes caused by disease in

tissues and body fluids.

Pancreatic Mass

– Abdominal/back pain

– Jaundice

– Dark urine/light stool

– Fatigue

– Fullness after eating

– Weight loss

– New onset or worsening

diabetes

– Solid mass

– Anywhere in the pancreas, most

common in the pancreatic head

(pancreas surrounded by the

duodenum)

– Irregular borders

Symptoms Radiological Imaging

HeadHeadHeadHead BodyBodyBodyBody TailTailTailTail

PancreasPancreasPancreasPancreas

No symptoms

– Radiological imaging for

another reason

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Diagnosis

Clinical diagnosis

(radiologist, gastroenterologist and surgeon)

– Symptoms

– Radiological imaging

– History of past illness

– History of family illness

– Physical examination

Diagnosis

Pathological Diagnosis

(Pathologist)

– Blood tests (clinical pathology)

– Tissue tests (anatomic pathology)

• Examination of cells (cytology) or tissue (histology)

under the microscope

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Normal Pancreas

Histology for Pathologists, S. Mills. LWW

HEAD BODY TAIL

Normal Pancreas Histology

•Exocrine Pancreas (enzymes)

•Acinar cells

•Ductal cells

•Endocrine Pancreas (hormones, e.g. insulin)

•Islet cells

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Pre-Operative Biopsy

– Pathology confirms clinical diagnosis of pancreatic

cancer

– Pathology makes the diagnosis when clinical

features are unclear

– Tissue diagnosis is required for therapy with

radiation and/or chemotherapy

– Tissue diagnosis is required for enrollment in

clinical trials

EUS-FNA(endoscopic ultrasound-guided fine needle aspiration biopsy- performed by the

gastroenterologist, interpreted (diagnosed) by the pathologist)

Pitman MB. Pancreas Cytology in Diagnostic Cytopathology, 3rd edition. Winifred Gray and Gabrijela Kocjan, eds. Elsivier.2010.

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EUS-FNA

The National Pancreas Foundation

Pre-Operative Pathology(Cytology)

Diagnosis: Pancreatic Ductal adenocarcinoma

https://therestlesslegsblog.wordpress.com/2010/04/

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Pre-Operative Diagnosis

Benign Malignant

Pre-Operative Diagnosis

Ductal Adenocarcinoma Neuroendocrine Tumor

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Pre-Operative Therapy

• Neoadjuvant therapy (chemotherapy or

chemoradiation therapy)

– Early treatment of micrometastatic disease

• Patient tolerance is better than post-operative

– May reduce tumor progression

– May induce tumor regression

• improves chances of clear surgical margins (R0)

– Allows pathologists to assess sensitivity of the

tumor to the therapy in operative patients

Bittoni, et al. Neoadjuvant Therapy in Pancreatic Cancer: An emerging Strategy. Gastroenterology Research and Practice , 2014)

Post-Operative Pathology(Histology)

Whipple Specimen (http://www.uwhealth.org/liver-pancreas-bile-duct-disorders/pancreatic-head-resection/26267)

http://www.slideshare.net/drferzli/trocar-port-placementforproceduregeneralstrategies

Whipple Resection Distal Pancreatectomy

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Tissue Processing

http://amida13.isi.uu.nl/?q=node/2

Pathological Diagnosis and Staging

• Tumor type

• Tumor size

• Tumor extent

• Surgical margins

• Lymph node involvement

• Distant spread (metastasis)

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Pathological Diagnosis: Tumor Type

• Ductal Adenocarcinoma (~90%)

AFIP Atlas of Tumor Pathology; 4th Series Fascicle 6


• Neuroendocrine Tumors (~10%)


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• Rare other types

– Solid-pseudopapillary neoplasm

– Acinar cell carcinoma

– Pancreatoblastoma

– Lymphoma

– Sarcoma


Solid-pseudopapillary neoplasm

Fine needle aspiration biopsy

Pathological Diagnosis: Tumor Size

Pea, cherry, walnut, and kiwi show tumor sizes.

www.pancreaticcancer.net.au

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Pathological Diagnosis

• Careful evaluation of

the surgical specimen

– Visual inspection of

tissue may not equate to

tumor under the

microscope

– Tumor and fibrosis are

both firm tissues

– Malignant glands can

extend beyond what is

seen as firm white tissueDuctal adenocarcinomaAFIP Atlas of Tumor Pathology; 4th Series Fascicle 6

Pathological Diagnosis: Tumor Extent

and Surgical Margins

http://www.rcpa.edu.au/Library/Practising-Pathology/Macroscopic-Cut-Up/Specimen/Gastrointestinal/Pancreas/Pancreas-resection

Cancer invasion of a nerve

Cancer invasion of a small vessel

Ductal adenocarcinomaAFIP Atlas of Tumor Pathology; 4th Series Fascicle 6

Cancers 2010, 2(4), 2001-2010

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Pathological Diagnosis: Lymph Node

involvement

http://medcell.med.yale.edu

Pathological Diagnosis: Metastasis

• Requires biopsy of distant tissue site and

diagnosis of cancer consistent with origin in

the pancreas: most common

– Liver

– Lung

– Adrenal glands

– Skin

Fine needle aspiration biopsy

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Pathological Staging:TNM Classification System

pT1 pT2

pT4N1

pT3

http://www.cancerresearchuk.org

American Joint Committee on Cancer(AJCC, 7th edition)

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Pathology Report

• Tumor Type– Ductal adenocarcinoma

– Neuroendocrine tumor

– Other

• Tumor Grade– Low grade or high grade

• Tumor extent

• High-risk histological findings– Invasion of the blood

vessels, lymphatic system, nerves

• Tumor Stage

Patient Care Team

Microscope Clipart by ben : Science Cliparts #17424- ClipartSE

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Thank you

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(877) 272-6226 or e-mail [email protected].

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Surgical Techniques & Interpretation

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