Pancreas Cancer Nimisha K. Parekh, MD, MPH Director, Inflammatory Bowel Disease Program H. H. Chao Comprehensive Digestive Disease Center Assistant Professor of Clinical Medicine University of California Irvine

Pancreas The pancreas is an organ located in the upper middle of the abdomen. It is surrounded by the stomach, small intestine, liver and spleen. Pancreatic cancer occurs when there is an uncontrolled growth of abnormal cells in the pancreas or ducts. The exact cause of pancreatic cancer are still largely unknown

The Facts 38,000 Americans will be diagnosed with pancreatic cancer this year 34,000 will die from the disease this year pancreatic cancer is the 4th leading cause of cancer-related death in the US 5-year survival rate is 5 percent Seventy-five percent of pancreatic cancer patients die within the first 12 months of the diagnosis Nearly 38,000 Americans will be diagnosed with pancreatic cancer this year, and over 34,000 will die from the disease. The incidence among African-Americans is 40 to 50 percent higher than other ethnic groups. Pancreatic cancer is one of the few cancers for which survival has not improved substantially over the past 30 years. As a result, in 2003, pancreatic cancer surpassed prostate cancer as the 4th leading cause of cancer-related death in the United States. Seventy-five percent of pancreatic cancer patients die within the first 12 months of the diagnosis. The 5-year survival rate is 5 percent.

The Facts Low survival rates are due to the fact that fewer than 10% of patients' tumors are confined to the pancreas at the time of diagnosis In most cases, the tumor has progressed to the point where surgery is impossible. Survival Rates According to the American Cancer Society, for all stages of pancreatic cancer combined, the one-year relative survival rate is 20%, and the five-year rate is 4%. These low survival rates are attributable to the fact that fewer than 10% of patients' tumors are confined to the pancreas at the time of diagnosis; in most cases, the malignancy has already progressed to the point where surgical removal is impossible. In those cases where resection can be performed, the average survival rate is 18 to 20 months. The overall five-year survival rate is about 10%, although this can rise as high as 20% to 25% if the tumor is removed completely and when cancer has not spread to lymph nodes.

Types of Pancreatic Tumors Ductal Adenocarcinomas (85%) Two thirds in head of pancreas Undifferentiated carcinomas Acinar cell carcinomas (1-2%) Sarcomatoid carcinoma/Carcinosarcoma (<1%) Serous cystic neoplasms Mucinous cystic neoplasms Intraductal papillary mucinous neoplasms NeuroEndocrine

Who should be screened? Not everyone should be screened for pancreatic cancer. Screening makes sense for people who are at risk for the disease typically because of hereditary factors or genetic syndromes that increase the likelihood of developing pancreatic cancer. Not everyone should be screened for pancreatic cancer. Screening makes sense for people who are at risk for the disease typically because of hereditary factors or genetic syndromes that increase the likelihood of developing pancreatic cancer.

Factors that Increase an Individual's Risk for Pancreatic Cancer Cigarette Smoking Alcohol BMI/Obesity Physical Activity Diabetes?? Gender (M>F) Family History Genetic Syndromes associated with pancreas cancer The following factors are known to increase the risk of developing pancreatic cancer; age, gender, race, cigarette smoking, diet, diabetes, environment and family history.

Family History Risk Factors Two or more first-degree relatives (parents, sibling, child) with pancreatic cancer One first-degree relative diagnosed with pancreatic cancer at an early age (under the age of 50) Two or more second-degree relatives (grandparent, aunt/uncle, niece/nephew, half-sibling) with pancreatic cancer, one of whom developed it at an early age History of a cancer syndrome associated with pancreatic cancer Factors that Increase an Individual's Risk for Pancreatic Cancer: Two or more first-degree relatives (parents, sibling, child) with pancreatic cancer One first-degree relative diagnosed with pancreatic cancer at an early age (under the age of 50) Two or more second-degree relatives (grandparent, aunt/uncle, niece/nephew, half-sibling) with pancreatic cancer, one of whom developed it at an early age History of a cancer syndrome associated with pancreatic cancer

Genetic Syndromes Associated with Pancreatic Cancer Genetic Mutation Clinical Clues Hereditary Pancreatitis PRSSI History of early pancreatitis (inflammation of the pancreas) of unknown cause Breast-ovarian cancer syndrome BRCA2 History of breast and/or ovarian cancer Hereditary nonpolyposis colorectal cancer syndrome Mismatch repair genes Personal or family history of early colorectal cancer Familial atypical multiple mole melanoma syndrome (FAMMM) CDK2NA/p16 Multiple melanomas with or without history of pancreatic malignancy Peutz-Jeghers syndrome STK11/LKB1 Benign polyps of the gastrointestinal tract with pigmented macules on the lips, inner lining of the cheeks, and hands/feet Genetic Syndromes Associated with Pancreatic Cancer

Diagnosis CT Scans MRI ERCP Endoscopic Ultrasound Laparascopy

Helical CT and MRI/MRCP

MRCP: Pancreatic Cancer Barish, NEJM, July 1999

EUS-Guided FNA Nodal staging Distant Metastasis Mediastinal: esophageal, lung Abdominal/celiac: gastric, pancreas Pelvis: rectal Distant Metastasis Liver Pleural/abdominal fluid Adrenal EUS-guided FNA has also been applied for the tissue confirmation of enlarged lymph nodes as well as metastatic lesions. Frank Gress has just presented this study on mediastinal lung staging in lung cancer. Abdominal, esp celiac nodes are important in staging GI malignancies. Pelvic nodes can be sampled thru the rectum And now, even metastasis to the liver, pleural/abd fluid and adrenal can be confirmed by FNA.

Pancreatic Body Mass UCSF Patient – MRCP – x 2; ERCP non-diagnostic; CT negative

ERCP vs. EUS for Pancreatic Masses Most Sensitive (well over 90%) NCI recommends this over CT guided biopsy ERCP Diagnostic Yield between 40-70% Image courtesy of Van Dam and Brugge, NEJM, 2003

Pancreatic Cancer - Detection EUS detected all tumors less than 2cm Schoefer et al, Abstract 1530, DDW 2000

Staging of Pancreas Tumors Stage I. Cancer is confined to the pancreas. Stage II. Cancer has spread beyond the pancreas to nearby tissues and organs and may have spread to the lymph nodes. Stage III. Cancer has spread beyond the pancreas to the major blood vessels around the pancreas and may have spread to the lymph nodes. Stage IV. Cancer has spread to distant sites beyond the pancreas, such as the liver, lungs and the lining that surrounds your abdominal organs

Treatments Surgery Radiation Chemotherapy Combination of above pancreatic cancer is treated either surgically, through radiation, chemotherapy, or a combination of these techniques

Anatomy of a Whipple Decrease in operative mortality over the last two decades Numerous studies have shown distinct association between patient volume and decreased mortality rates High volume institutions report rates of 3 to 15% for pancreatic cancer Minimum number per year of 11

Final Points Familial Pancreatic Cancer /National Familial Pancreas Tumor Registry Hirshberg Foundation for Pancreatic Cancer Research NIH UCLA, UCI, City of Hope have pancreas programs Healthy lifestyle