Textbook of Medical-Surgical Nursing 3e

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Unit 3   Applying concepts from the nursing process

rapidly stimulate formation of new blood vessels, which helps malignant cells obtain the necessary nutrients and oxygen. It is also through this vascular network that tumour emboli can enter the systemic circulation and travel to distant sites. Large tumour emboli that become trapped in the microcirculation of distant sites may further metastasise to other sites. Therapies that target VEGF or its receptors are being used to treat many cancers effectively (see Targeted therapies discussed later in this chapter). Malignant transformation, or carcinogenesis , is thought to be at least a three-step cellular process: initiation, promotion and progression. Agents that initiate or promote cellular transfor- mation are referred to as carcinogens. In initiation, the first step, initiators (carcinogens), such as chemicals, physical factors and biological agents, escape normal enzymatic mechanisms and alter the genetic struc- ture of the cellular DNA. Normally, these alterations are reversed by DNA repair mechanisms or the changes initiate programmed cellular suicide (apoptosis). Occasionally, cells escape these protective mechanisms and permanent cellular mutations occur. These mutations usually are not significant to cells until the second step of carcinogenesis. During promotion, repeated exposure to promoting agents (co-carcinogens) causes the expression of abnormal or mutant genetic information even after long latency periods. Latency periods for the promotion of cellular mutations vary with the type of agent and the dosage of the promoter as well as the innate characteristics of the target cell. Cellular oncogenes, present in all mammalian systems, are responsible for the vital cellular functions of growth and differentiation. Cellular proto-oncogenes are present in cells and act as an ‘on switch’ for cellular growth. Proto-oncogenes are influenced by multiple growth factors that stimulate cell proliferation, such as epidermal growth factor (EGF) and transforming growth factor alpha. Another proto-oncogene that plays an important role in cancer development is the k-ras (KRAS2) oncogene located on chromosome 12. Similarly, cancer suppressor genes ‘turn off’ or regulate unneeded cellular proliferation. When the suppressor genes become mutated, rearranged or amplified or lose their regula- tory capabilities, malignant cells are allowed to reproduce. The p53 (TP53) gene is a tumour suppressor gene that is frequently mutated in many human cancers. This gene regu­lates whether cells will repair or die after DNA damage. Apoptosis is the innate cellular process of programmed cell death. Alterations in TP53 may decrease apoptotic signals, thus giving rise to a survival advantage for mutant cell populations. Mutant TP53 gene is associated with a poor prognosis and may be associated with determining response to treatment. Once this genetic expression occurs in cells, the cells begin to produce mutant cell populations that are different from their original cellular ancestors. Progression is the third step of cellular carcinogenesis. The cellular changes formed during initiation and promotion now exhibit increased malignant behaviour. These cells now show a propensity to invade adjacent tissues and to metastasise. Agents that initiate or promote cellular transformation are referred to as carcinogens. Carcinogenesis Molecular process

Aetiology Categories of agents or factors implicated in carcinogenesis include viruses and bacteria, physical agents, chemical agents, genetic or familial factors, dietary factors and hormonal agents. Viruses and bacteria Viruses as a cause of human cancers are hard to determine because viruses are difficult to isolate. Infectious causes are considered or suspected, however, when specific cancers appear in clusters. Viruses are thought to incorporate them- selves in the genetic structure of cells, thus altering future gen- erations of that cell population—perhaps leading to a cancer. For example, the Epstein-Barr virus is highly suspect as a cause in Burkitt’s lymphoma, nasopharyngeal cancers, and some types of non-Hodgkin’s lymphoma and Hodgkin’s disease. Herpes simplex virus type II, cytomegalovirus, and human papilloma virus types 16, 18, 31 and 33 are associated with dys- plasia and cancer of the cervix. The hepatitis B virus is impli- cated in cancer of the liver; the human T-cell lymph­otropic virus may be a cause of some lymphocytic leukaemias and lymphomas; and the human immunodeficiency virus (HIV) is associated with Kaposi’s sarcoma. The bacterium Helicobacter pylori has been associated with an increased incidence of gastric malignancy, perhaps secondary to inflammation and injury of gastric cells. Bacteria have been evaluated as a cause of cancer over the years but with little evidence to support the link of bacteria to cancer. Chronic inflammatory reactions to bacteria and the production of carcinogenic metabolites are possible mechanisms under investigation. In the early 1990s, the International Agency for Research on Cancer (IARC) iden- tified Helicobacter pylori ( H. pylori ) as the first bacterium to be termed a definite cause of cancer in humans. H. pylori has been associated with an increased incidence of gastric malignancy related to chronic superficial gastritis, with resultant atrophic and metaplastic changes to the gastric mucosa (Schottenfeld & Beebe-Dimmer, 2006). Physical agents Physical factors associated with carcinogenesis include exposure to sunlight or radiation, chronic irritation or inflam- mation and tobacco use. Excessive exposure to the ultraviolet rays of the sun, espe- cially in fair-skinned, blue- or green-eyed people, increases the risk for skin cancers. Factors such as clothing styles (sleeveless shirts or shorts), use of sunscreens, occupation, recreational habits and environmental variables, including humidity, altitude and latitude, all play a role in the amount of exposure to ultraviolet light. Exposure to ionising radiation can occur with repeated diagnostic x-ray procedures or with radiation therapy used to treat disease. Fortunately, improved x-ray equipment appro- priately minimises the risk for extensive radiation exposure. Radiation therapy used in disease treatment or exposure to radioactive materials at nuclear weapon manu­facturing sites or nuclear power plants is associated with a higher incidence of leukaemias, multiple myeloma, and cancers of the lung, bone, breast, thyroid and other tissues. Background radiation from the natural decay processes that produce radon has also been associated with lung cancer. Homes with high levels of trapped radon should be ventilated to allow the gas to disperse into the atmosphere.