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When clinicians use the term pancreatic cancer, they refer to adenocarcinoma of the pancreas, one of the most challenging malignancies facing oncologists today. This disease is characterized by significant morbidity and poor prognosis. During the course of illness, a variety of problems may beset the patient and confront the clinician. At The University of Texas MD Anderson Cancer Center (MDACC), we manage pancreatic cancer patients with a multidisciplinary team and view palliation as the primary goal. However, for patients with potentially resectable disease, we take an aggressive multimodality approach whenever medically appropriate. In the setting of advanced disease, cure is not possible, but as our understanding of the underlying molecular events involved in carcinogenesis, invasion, and metastasis expands, more effective therapeutic strategies are expected to emerge. Therefore, whenever feasible, patients with advanced disease are treated in clinical trials with special emphasis on targeted therapy. This chapter reviews our current knowledge about pancreatic cancer, including its epidemiology, risk factors, molecular biology, diagnosis and staging, and clinical strategies for current and future therapies.

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Hard Facts About Pancreatic Cancer

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Pancreatic cancer, the most common pancreatic neoplasm, is an aggressive and often rapidly fatal malignancy. In the United States, it represents only 2% of all cancer cases but accounts for 5% of all cancer deaths (1). Currently, it is the fourth leading cause of cancer death, ranking only behind lung cancer, colorectal cancer, and breast cancer. While recent evidence suggests marginal improvements in 5-year survival rates over the last 25 years (2% in 1974-1976, 3% in 1983-1985, and 4% in 1992-1997), life expectancy remains short and is generally measured in months (2). Significant improvements in survival have been hampered by a number of factors, including inefficient and ineffective screening strategies, resulting in frequent presentation with advanced disease, technically challenging and often debilitating surgery (which is commonly misapplied), and minimally effective chemotherapy and radiotherapy.

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Moreover, pancreatic cancer is a dynamic disease, and sudden changes in clinical status occur frequently. Patients may rapidly develop worsening pain, biliary obstruction, or stent occlusion with cholangitis, gastrointestinal bleeding, thromboembolism, gastric outlet obstruction, or peritoneal carcinomatosis with intestinal dysmotility or intractable ascites. Any of these problems may preclude the timely delivery of cytotoxic therapy and limit opportunities to alter survival. Therefore most efforts should focus on symptom control, but for patients with adequate performance status, treatment is encouraged.

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Epidemiology

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There are approximately 30,000 new cases of pancreatic cancer each year in the United States and 170,000 cases worldwide. Overall, the incidence and mortality of pancreatic cancer are similar throughout the world, but incidence rates are highest in industrialized societies and Western countries. Of particular note is the risk of pancreatic cancer among African Americans, in whom pancreatic cancer mortality rates are higher than for most other ethnic groups in the United States and considerably higher than the rates for African blacks (3). This ...

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