current management of pancreatic cancer … · current management of pancreatic cancer. mark s....

Current Management of Pancreatic Cancer

Mark S. Talamonti, MDChairman, Department of Surgery

NorthShore University HealthSystemUniversity of Chicago Medical School

Pancreas Cancer: Biologic ChallengesMolecular Genetics

Alteration % Expression

Tumor SuppressorInactivation

p53P16/CDKN2ADPC4/SMAD4

758050

OncogeneActivation

k-ras 80-100

DNA MismatchRepair Mutations

hMSH2, hMLH1, hPMS1, hPMS2, hMSH6, hMSH3

4

Growth Factor Expression

EGF, TGF-B,FGF, IGF-1

Molecular Heterogeneity & Diversity

Most complicated & intense

stromal–epithelial interaction

PREDISPOSINGFACTORS Increased Risk Possible Risk Unproven Risk

Demographic FactorsAdvancing Age

Black raceMale gender

Jewish religion

Geography Socioeconomic statusMigrant status

HostFactors

HNPCCBRCA 2

Peutz-JeghersAtaxia-telangiectasia

FAMMMHereditary pancreatitis

DiabetesChronic PancreatitisEndocrine Tumors

Cystic fibrosisSex Hormones

Pernicious anemia

Peptic ulcer surgeryCholecystectomy

EnvironmentalFactors

Tobacco DietOccupation

AlcoholCoffee

Radiation

RISK FACTORS

Increasing Frequency & Relevancy

Smith BD, et al. Future of cancer incidence in the US: burdens upon an aging changing nation.JCO, 2009

55%

Anatomic Site at Presentation

Head

Body

Tail

Head-Body

Body-Tail

Diffuse

61%

13%

15%5%

Cubillo, JSO, ‘78302 PATIENTS

Common Clinical Manifestations of Pancreatic Cancer

• Abdominal pain or abdominal pain radiating to back

• Weight loss, anorexia• Diarrhea, nausea/vomiting• Jaundice• New onset diabetes• Depression

Staging Pancreatic Cancer

Optimize treatment for subgroups of patients

• localized and resectable or borderline resectable

• localized but unresectable

• distant metastases

Avoid redundant or unnecessary procedures

Prevent excessive testing and expenditures

RESECTABLE

<180º

TUMOR ABUTS SMV < 180o, NOT SMA

MESENTERIC “TEAR DROP” SIGN

BORDERLINE RESECTABLEMesenteric Artery Abutment

TUMOR ENCASES SMA

UNRESECTABLE

360º

TUMORNeedle

PANCREATIC CARCINOMA

Surgical Advances and Current Controversies

The Whipple Procedure

Standard Whipple

Pyloric-preserving Whipple

Vascular Resection

Recent Series of Long-term Survivors

Series No. pts. Stages included

R0Resection

(%)

AdjuvantTreatment

(%)

Median OS

survival (mo)

Actual 5-year

survivors (%)

Johns Hopkins,

2006564 nr nr nr 18 17

MAYO, 2008 357 pr, la, m 77 77 17 17

MSKCC, 2008 618 pr 73 21 nr 12

MDACC, 2009 329 pr, br 84 91 24 27

Katz et al., Ann Surg Onc, 2009

Intergroup Alliance AO21101

Hopkins, Mayo, MDACC, NorthShore/U of C, Cincinnati, Louisville, VanOhio State, Wisconsin, UC-San Diego

Complications and Consequences

• Short-term complications after surgery– Pulmonary

• Pneumonia• Pulmonary Embolism

– Hemorrhage• Gastrointestinal• Intra-abdominal

Complications and Consequences

• Short-term complications after surgery– Infections

• Wound infections• Intra-abdominal abscess and pancreatic anastomotic leaks

(pancreatic fistula)

– Delayed gastric emptying and malnutrition

Complications and Consequences• Long-term consequences of surgery

– Gastric problems• Reflux, ulcers, dumping syndrome, early satiety

– Pancreas problems• Diabetes or glucose intolerance• Pancreatic enzyme insufficiency

– Nutrition and weight loss• Dietary modifications• Nutritional supplements