Handbook of Genetic Counseling/Pancreatic Cancer

Pancreatic Cancer

Pancreatic Cancer

 * Incidence is more than 29,000 new cases/year in US
 * Fifth leading cause of cancer death
 * 4.1% five-year survival rate is lowest of all cancers
 * About 9-10% of pancreatic cancer is familial
 * Pancreas is a gland located in the abdomen between the stomach and the spine
 * Responsible for producing insulin, glucagon, and other hormones
 * Releases digestive juices through series of ducts leading to common bile duct
 * Risk factors for pancreatic cancer
 * Smoking - increases risk 2-3 times
 * Age - most cancers diagnosed between 60 and 80 years
 * Diabetes
 * Chronic pancreatitis
 * Long-term inflammation of the pancreas
 * Especially inherited form of the condition
 * Family history
 * Risk increases by 4.7% if first degree relative has been diagnosed
 * Increases by 7.3% if diagnosis was made before age 60
 * Increases by 12.3% if multiple primary cancers in family
 * Males and African-Americans may be at increased risk
 * Diets high in fat may increase risk

Diagnosis and Surveillance Options

 * Possible symptoms
 * Pain in upper abdomen or upper back
 * Yellowing of skin and eyes, dark urine due to jaundice
 * Weakness
 * Loss of appetite
 * Nausea and vomiting
 * Weight loss
 * Physical exam
 * Look for signs of jaundice or changes in area near pancreas
 * Check for ascites (build-up of fluid in abdomen)
 * Lab tests
 * Blood, urine, and stool samples
 * Check for bilirubin that may be high if tumor blocking common bile duct prevents its passage
 * CT Scan
 * Produces detailed picture of abdomen
 * Can provide information about nature and location of tumors, resectability
 * Ultrasonography
 * Transabdominal ultrasound
 * Endoscopic ultrasound (EUS)
 * Pass thin, illuminated optic instrument down mouth into stomach
 * Ultrasound device at tip of endoscope takes images of pancreas and surrounding areas
 * Endoscopic Retrograde Cholangiopancreatography (ERCP)
 * Pass endoscope through mouth and stomach into first part of small intestine
 * Inject dye through catheter into ducts
 * Take X-rays to determine if ducts are narrowed or blocked by tumor
 * Percutaneous Transhepatic Cholangiography (PTC)
 * Dye injected through needle inserted through skin into liver
 * Dye moves freely through bile ducts unless blocked
 * X-rays can show if dye has moved through ducts
 * Biopsy
 * Fine-needle aspiration
 * During EUS or ERCP
 * Open abdomen during operation
 * Laparoscopy
 * Uses several small incisions and TV camera to visualize organs in abdomen
 * Usually only used if CT scan shows evidence of metastases

Treatment

 * Pancreatic cancer is currently difficult to treat so participation in clinical trials is often recommended
 * Surgery
 * May be used alone or in combination with radiation or chemotherapy
 * Whipple procedure
 * If tumor is in head of pancreas
 * Remove head and part of small intestine, bile duct, and stomach
 * Distal pancreatectomy
 * Surgeon removes body and tail of pancreas
 * May also remove the spleen
 * Total pancreatectomy
 * Remove entire pancreas
 * Also remove part of small intestine and stomach, and all of common bile duct, gallbladder, spleen, and nearby lymph nodes
 * Create bypass or insert stent if tumor is blocking common bile duct or duodenum
 * Relives jaundice and pain resulting from blockage
 * Done if cancer cannot be completely removed surgically
 * Side effects of removal of all or part of pancreas
 * Diet control and medication may help with food digestion
 * Diarrhea, pain, cramping, and feelings of fullness are common
 * Radiation therapy and chemotherapy often used to destroy cancer cells

Genetic Conditions Associated with Pancreatic Cancer

 * Familial Atypical Multiple Mole Melanoma (FAMMM)
 * Due to mutations in p16 tumor suppressor gene
 * TP16 (CKDN2) located at 9p21
 * Affected individuals develop multiple nevi, atypical nevi, melanomas, and pancreatic cancer
 * Peutz-Jeghers Syndrome
 * Due to mutations in LKB1 (STK11) gene at 19p13.3
 * Causes multiple hamartomaous polyps of GI tract and pigmented macules on lips, buccal mucosa, and digits
 * Increases risk to develop cancers
 * In women: breast, pancreas, uterus, and ovary
 * In men: colon, pancreas, lung, or testes
 * Hereditary Breast-Ovarian Cancer Syndrome
 * Due to mutations in BRCA2 tumor suppressor gene at 13q12
 * Most common inherited predisposition to pancreatic cancer identified to date
 * Mutations in BRCA2 have been identified in individuals with no family history of breast or ovarian cancer
 * Estimated that carriers of 6174delT have 10-fold increased risk of developing pancreatic cancer
 * Increases risk for breast, ovarian, prostate, and colon cancers also
 * HNPCC
 * Due to mutations in mismatch repair genes, including MSH2 and MLH1
 * Microsatellite instability has been identified in ~4% of pancreatic cancers
 * Should be considered in patients with family history of colon cancer
 * Increases risk for colon/rectum, endometrium, ovarian, urinary tract, stomach, and small intestine also
 * MEN1
 * Due to mutations in menin tumor suppressor gene at 11q13
 * Associated specifically with insulinomas (10%) or gastrinomas (40%)
 * Can cause tumors on parathyroid and pituitary glands also
 * Hereditary Pancreatitis
 * Due to mutations in cationic trypsinogen gene on 7q35
 * Block inactivation of trypsin, resulting in autodigestion of pancrease
 * Increase in pancreatic cancer may be secondary to chronic injury and repair
 * Clinical testing available through University of Pittsburgh
 * Penetrance of mutations is only 80%

Psychosocial Issues

 * Worry about the future - caring for themselves, family, etc.
 * Financial concerns
 * Concerns about treatments and side effects
 * Concern about necessity of frequent hospital visits, home care, etc.
 * Feelings of guilt, anxiety, fear surrounding potential diagnosis of hereditary syndrome

Resources

 * The National Familial Pancreas Tumor Registry
 * Dr. Ralph H. Hruban, Director
 * Baltimore, MD 21231-2410
 * Phone: (410) 955-9132


 * Hereditary Pancreatitis Registry
 * Dr. Whitcomb or Dr. Lowenfels
 * The Midwest Multicenter Pancreatic Study Group
 * Phone: 888-PITT-DNA


 * National Cancer Institute
 * Phone: 1-800-4-CANCER
 * http://cancer.gov