Pancreatic Cancer

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Contents 1 More Specific Terms 2 Etiology 3 Epidemiology 4 Genetics 5 Clinical-manifestations 6 Laboratory 7 Diagnostic-procedures 8 Radiology 9 Complications 10 Management 11 More General Terms 12 Additional Terms 13 Internet Database 14 References

More Specific Terms

• pancreatic adenocarcinoma

Etiology

• ductal adenocarcinoma 90%
• endocrine neoplasms
• connective tissue neoplasm
• acinar cell neoplasm
• epidermoid neoplasm
• mixed cell tumors
• risk factors:

• diabetes mellitus
• chronic pancreatitis
• hereditary pancreatitis
• carcinogens

• benzidine
• cigarette smoking

• alcohol
• high-fat diet
• early adult obesity or excess weight [6]

Epidemiology

• more common in men than women
• generally presents between ages 60-80
• 4th leading cause of cancer death in USA [5]

Genetics

• chromosomal inversion(s) found in nearly all metastatic pancreatic cancer [7]
• telomeres are dysfunctional, control of cell cycle is lost
• intiation of pancreatic cancer begin 15 years prior & metastasis 5 years prior to clinical presentation [7]
• defects in SMAD4 are a cause of pancreatic carcinoma
• overexpression of: TM4SF5, LSM1
• implicated genes MLL4, WDR45, ANKRD37, IGF2BP3, MGAT4A, MGAT4B, AMIGO2, SULF1, HES2, ANLN, WIPI2, HCC1, TBRG1, ARID4B, LRRC26, OLFM4, PALLD, MTUS1, BCL9L, ARHGAP27, S100PBP, PTPRH, MUC17, NT5DC3, PEG10, ZNF146, CCKBR, CD97, PLXNB1, GNG7, RAB20, S100P, TSPAN8, BIRC5

Clinical-manifestations

• generally presents late in the course of the disease
• presenting signs & symptoms

• frequent

• prodrome of malaise, anorexia & weight loss
• upper abdominal pain, back pain
• jaundice (lesion of head of pancreas)

• infrequent

• glucose intolerance ( diabetes mellitus)
• palpable gallbladder ( Courvoisier's sign)
• migratory thrombophlebitis, superficial vein thrombosis ( Trousseau's syndrome)
• gastrointestinal hemorrhage
• splenomegaly

• may present as depression

• non- bacterial ( thrombotic) 'marantic' endocarditis
• hepatomegaly, ascites, abdominal mass
• left suprclavicular adenopathy

Laboratory

• non-specific elevations in serum transaminases, alkaline phosphatase, amylase may be present
• anemia is variable
• serum CA 19-9 > 800 ug/mL indicates a poor prognosis ( tumor markers not used for diagnosis) [3]

Diagnostic-procedures

• endoscopic retrograde cholangiopancreatography ( ERCP)

• biopsy with histopathology or cytology

Radiology

• abdominal ultrasound, evaluation of pancreatic & bile ducts
• computed tomography ( CT) imaging modality of choice [3]

• evaluation of pancreatic & bile ducts
• pancreatic mass, calcifications

• endoscopic ultrasonography
• 'double-duct' sign: obstruction of both the pancreatic & bile ducts
• percutaneous transhepatic cholangiopancreatography

Complications

• 
  
• disease interaction(s) of cancer with Alzheimer's disease

Management

• neoadjuvant chemotherapy with or without radiation typically used for locally advanced pancreatic cancer
• surgical resection affords the only hope of cure

• most lesions are non-resectable
• criteria for resection

• tumor < 2 cm
• absence of lymph node invasion
• absence of metastases

• surgical procedures:

• Whipple procedure
• total pancreatectomy
• survival is the same

• palliative surgery

• intraoperative chemical splanchnicectomy
• endoscopic biliary stent placement for obstructive jaundice
• expandable stent of gastrojejunostomy for relief of bowel obstruction
• celiac nerve block when systemic analgesics are not effective

• radiation therapy may have some role, but survival is unchanged
• chemotherapy has not been very useful

• gemcitabine plus daily oral erlotinib [5] for metastases

• protocols include:

• 5-fluorouracil
• 5-fluorouracil or gemcitabine with radiation therapy [3]

• prognosis:

• 5 year survival < 6%
• median survival with metastatic disease 3-6 months

More General Terms

• malignant neoplasm (cancer)

Additional Terms

• cancer antigen CA 19-9 (carbohydrate antigen 19-9) in serum
• Courvoisier's sign
• Trousseau's syndrome

Internet Database

OMIM: 606856
OMIM: 260350

References

1. Saunders Manual of Medical Practice, Rakel (ed), WB Saunders, Philadelphia, 1996, pg 382-83
2. Mayo Internal Medicine Board Review, 1998-99, Prakash UBS (ed) Lippincott-Raven, Philadelphia, 1998, pg 315
3. Medical Knowledge Self Assessment Program (MKSAP) 11, 14, 15, American College of Physicians, Philadelphia 1998, 2006, 2009
4. Harrison's Principles of Internal Medicine, 14th ed. Fauci et al (eds), McGraw-Hill Inc. NY, 1998, pg 582
5. Moore MJ, Goldstein D, Hamm J, Figer A, Hecht JR, Gallinger S, Au HJ, Murawa P, Walde D, Wolff RA, Campos D, Lim R, Ding K, Clark G, Voskoglou-Nomikos T, Ptasynski M, Erlotinib Plus Gemcitabine Compared With Gemcitabine Alone in Patients With Advanced Pancreatic Cancer: A Phase III Trial of the National Cancer Institute of Canada Clinical Trials Group. J Clin Oncol. 2007 Apr 23; [Epub ahead of print] PMID: [1]
6. Li D et al Body mass index and risk, age of onset, and survival in patients with pancreatic cancer. JAMA 2009 Jun 24; 301:2553. PMID: [2]
7. Campbell PJ et al The patterns and dynamics of genomic instability in metastatic pancreatic cancer. Nature 2010 Oct 28; 467:1109 PMID: [3]
   - Yachida S et al Distant metastasis occurs late during the genetic evolution of pancreatic cancer. Nature 2010 Oct 28; 467:1114 PMID: [4]
   - Luebeck EG. Genomic evolution of metastasis. Nature 2010 Oct 28; 467:1053 PMID: [5]
8. Nieto J et al Metastatic pancreatic cancer 2008: is the glass less empty? Oncologist. 2008 May;13(5):562-76. Review PMID: [6]
9. Pancreatic Cancer: NIH Institute and Center Resources [7]
10. National Guideline Clearinghouse
    - Use of gemcitabine in the treatment of advanced pancreatic adenocarcinoma (Program in Evidence-based Care) ngc-guideline: [8]
    - Chemotherapy or radiotherapy for resectable pancreatic adenocarcinoma: clinical practice guidelines. ngc-guideline: [9]
    - PET imaging in pancreatic cancer: recommendations. Program in Evidence-based Care ngc-guideline: [10]

pancreatic cancer