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