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Primary malignant epithelial neoplasms of the pancreas are currently classified based on their phenotype into ductal, acinar, or neuroendocrine. Some remain unclassified as to their phenotype. Pancreatic ductal adenocarcinoma (PDAC) is the most common type, accounting for approximately 90% of the tumors [1].

Pancreatic cancer is the seventh leading cause of cancer deaths in the industrialized world and third most common in the USA [2]. Based on GLOBOCAN 18 estimates, it ranks as the eleventh most common cancer in the world, accounting for 4.5% of all deaths caused by cancer [2]. The highest mortality rates are in Western Europe (7.6 per 100,000 people), Central and Eastern Europe (7.3), and Northern Europe and North America equally (6.5). The lowest are in Eastern Africa (1.4) and South Eastern Asia and West Africa (2.1). Pancreatic cancer is trending to increase from 2018 to 2040 worldwide (+77.7% new cases and +79.9% deaths) [2].

The average lifetime risk of pancreatic cancer for both men and women is about 1 in 64 (1.6%). According to the American Cancer Society, about 57,600 people (30,400 men and 27,200 women) will be diagnosed with pancreatic cancer in the year 2020 and about 47,050 people will die of pancreatic cancer in the USA (www.cancer.org).

Table 1. Syndromes and their associated gene mutations

The incidence increases with age for both sexes [2]. Pancreatic cancer is usually present in patients older than 65 years of age, with a median age at diagnosis of 71 years. There is a slight preponderance in men. Risk factors associated with pancreatic cancer include older age, smoking, obesity, and exposure to certain chemicals used in dry cleaning and metal industries. Smoking is a firmly established risk factor for pancreatic cancer [3]. Compared to those who have never smoked, the overall risk is 1.40 for ever cigarette smokers, 1.17 for former cigarette smokers, and 2.2 for current cigarette smokers [3]. The risk of PDAC decreases with smoking cessation. Another potentially modifiable factor implicated in the development of pancreas cancer is a high body mass index (BMI). Insulin resistance is hypothesized as a mechanism contributing to this increase in risk in patients with a high BMI [4].

A family history of pancreatic cancer, usually defined as having at least one affected first degree relative, is seen in 5–10% of individuals with this disease [5, 6]. Risk is known to increase strongly in families with several members affected [7]. Familial pancreatic cancer characterizes families with an abnormally high rate of pancreatic cancer in which an inherited gene is suspected but has not been identified. Individuals with familial pancreatic cancer may have a specific genetic mutation that is linked to a syndrome which predisposes them to certain types of cancer. Mutations in a number of genes are related to increased risk of PDAC. Currently, at least twelve inherited gene mutations are known to increase the predisposition to pancreatic cancer [8]. The genetic syndromes included are hereditary breast and ovarian cancer syndrome, familial atypical multiple mole melanoma syndrome, familial pancreatitis, Lynch syndrome, and Peutz-Jeghers syndrome. PALB2 and ATM have recently been associated with familial cancers [8]. The inherited syndromes and gene mutations associated with pancreatic cancer are shown in Table 1a.

Other neoplasms and malignancies are less common. Pancreatic neuroendocrine tumors (PanNETs) comprise approximately 5% of pancreatic malignant tumors [1] and occur sporadically. PanNETs are rarely seen in children and adolescents, but when present are usually associated with a genetic/familial [9] predisposition such as multiple endocrine neoplasia 1 (MEN1), tuberous sclerosis, von Hippel-Lindau (VHL) disease, and neurofibromatosis (Table 1b). Acinar cell carcinoma (ACC) is a rare malignant neoplasm, comprising 1–2% of pancreatic malignant tumors with a mean age of presentation of 56 years [1]. Approximately 6% of ACCs occur in children between the ages of 8 and 15 years [1]. The clinical evolution of this neoplasm in children seems to be better than that observed in adults [10]. Pancreatoblastoma is a rare tumor comprising <1% of malignant pancreatic tumors that is said to have a bimodal peak first at 5 years and then at 40 years of age [1]. Solid-pseudopapillary neoplasm (SPN) comprises 1–2% of the pancreatic tumors [1] and occurs predominantly in young females.