Pancreatic cancer is the tenth most common malignancy, and is the fourth leading cause of cancer related mortality in both women and men in the western world. It is predicted that by year 2020 pancreatic cancer will surpass colon and liver cancer related mortality, making pancreatic cancer the second leading cause of cancer related death, placing it just behind lung cancer (8)(9). The American Cancer Society estimates 48,960 new cases of pancreatic cancer for year 2015, and is estimated that 40,560 of these patients will succumb to the disease (8). These numbers highlight the extremely dismal diagnosis of pancreatic cancer, which has a median survival <6 months and a 5-year survival rate below 5% (10). The majority of diagnosed pancreatic
…show more content…
The median age at which PDAC is diagnosis is 71 years, and is rarely diagnosed in people younger than 40 years of age (11)(15). At 80 years of age the risk factor for developing pancreatic cancer increases 40-fold (18). Computational models of PDAC that incorporate the number of somatic mutations, driver versus passenger events, and cellular proliferation as they acquire a cancerous phenotype, estimate that it takes an average of 11.7 years for initiating events that begin pancreatic carcinogenesis to develop into in situ cancer and a further 6.8 years for primary tumor to develop metastatic clones (19)(20). Once metastasis occurs patients succumb to the disease an average of 2.7 years later (21), and unfortunately the majority of pancreatic cancer patients are diagnosed during the late-stage of disease making it difficult to provide therapeutic intervention. However, if these computation models of PDAC development are correct, it provides a large opportunity for early detection and potential …show more content…
Most commonly, the disease arises in the pancreas head and infiltrates into surrounding tissues, such as the lymphatics, peritoneum, and spleen (32). The most common sites for distal metastasis are the liver and lung; however, PDAC metastasis has been reported in virtually all organs (33)(34)(35). PDAC develops via a progressive model, determined by histological and genetic pathology (Figure 1.2) (36)(19). The precursor lesions that eventually develop into bona fide PDAC are termed pancreatic intraepithelial neoplasia (PanIN). There are three classifications of PanIN and are characterized by increasing cytological atypia: PanIN-1, are composed of mucinous columnar epithelial cells with little cellular atypia; PanIN-2, are composed of papillary (rather than flat) epithelial and have some nuclear atypia; PanIN-3, have high-grade dysplasia and are referred to as carcinoma in situ (Figure 1.2)
The median age at which PDAC is diagnosis is 71 years, and is rarely diagnosed in people younger than 40 years of age (11)(15). At 80 years of age the risk factor for developing pancreatic cancer increases 40-fold (18). Computational models of PDAC that incorporate the number of somatic mutations, driver versus passenger events, and cellular proliferation as they acquire a cancerous phenotype, estimate that it takes an average of 11.7 years for initiating events that begin pancreatic carcinogenesis to develop into in situ cancer and a further 6.8 years for primary tumor to develop metastatic clones (19)(20). Once metastasis occurs patients succumb to the disease an average of 2.7 years later (21), and unfortunately the majority of pancreatic cancer patients are diagnosed during the late-stage of disease making it difficult to provide therapeutic intervention. However, if these computation models of PDAC development are correct, it provides a large opportunity for early detection and potential …show more content…
Most commonly, the disease arises in the pancreas head and infiltrates into surrounding tissues, such as the lymphatics, peritoneum, and spleen (32). The most common sites for distal metastasis are the liver and lung; however, PDAC metastasis has been reported in virtually all organs (33)(34)(35). PDAC develops via a progressive model, determined by histological and genetic pathology (Figure 1.2) (36)(19). The precursor lesions that eventually develop into bona fide PDAC are termed pancreatic intraepithelial neoplasia (PanIN). There are three classifications of PanIN and are characterized by increasing cytological atypia: PanIN-1, are composed of mucinous columnar epithelial cells with little cellular atypia; PanIN-2, are composed of papillary (rather than flat) epithelial and have some nuclear atypia; PanIN-3, have high-grade dysplasia and are referred to as carcinoma in situ (Figure 1.2)