Classification Causes Diagnosis Grading Staging Effects/Surgical Tx Cancer Classification Causes Diagnosis Grading Staging Effects/Surgical Tx

Objectives Discuss the pathophysiology of cancer. Differentiate between benign and malignant neoplasms Discuss causes of cancer Describe the lab and diagnostic tests used to diagnose cancer L & B p. 277

Pathophysiology Normal cell growth review The Cell Cycle: 4 phases A malfunction of any of the regulators of cell growth can result in rapid proliferation of immature cells Differentiation Etiology p. 275 L & B 1. Cell cycle G 1 phase: cell enlarges and synthesizes proteins to prepare for DNA replication—cell prepares to replicate Synthesis phase: DNA is replicated and the chromosomes in the cell are duplicated. Cell cycle G2 phase: cell prepares for mitosis. Cell begins mitosis, which culminates in division of parent cell into 2 exact copies called the daughter cells. Cycle repeats—is controlled by cyclins, which combine with and activate cyline – dependent kinases (CDKs). Some cyclins cause a braking action and stop the cycle from proceeding A malfunction of any of the regulators of cell growth can result in rapid proliferation of immature cells—these cells are considered cancerous or malignant. Differentiation is a normal process occurring over many cell cycles that allows cells to specialize in certain tasks. (Example of epithelial cells lining the lungs develop into tall columnar cells with cilia. The columnar cells sweep potential dangerous debris out of the lungs. When adverse conditions occur in body tissues occur during differentiation, protective adaptations can produce alterations in cells. Some are helpful but many cells may mutate beyond usefulness and become liabilities…ie hyperplasia, metaplasia, dysplasia, anaplasia Etiology: Much research (to include Human Genome Project) factors that cause cancer are both external (chemicals, radiation, and viruses) and internal (hormones, immune conditions, and inherited mutations). They may act together or in sequence to initiate or promote carcinogenesis. Ten ormore yrs often pass between exposures or mutations and detectable cancer.

Known Causes Viruses Drugs and Hormones Chemical Agents Physical Agents L & B p. 276-277 Viruses Drugs and Hormones Chemical Agents Physical Agents

Benign Neoplasms Localized growths Form a solid mass Well-defined borders Frequently encapsulated Response to homeostatic controls Grow slowly; same size Destructive with crowding/pressure L & B p. 278 When they respond to homeostatic controls, they stop growing because they reach the boundaries of another tissue. ( a process called inhibition). Because they are frequently encapsulated, they are easily removed and tend not to recur Although they are typically harmless, they can be destructive if they crowed surrounding tissue and obstruct function of other organs. --such as a benign meningioma (from the meninges of the brain and spinal cord) can cause severely increased ICP, which can progressively impair cerebral function. Unless removed, the steadily rising ICP will eventually lead to coma and death.

Malignant Neoplasms Grow aggressively Response to homeostatic controls Noncohesive; irregular shape Cut through surrounding tissues; Rapid Cells may travel thru blood or lymph Not always easy to remove Can recur p. 278 L & B Do not respond to homeostatic controls. Instead of crowding other tissues aside, malignant neoplasms cut thru surrounding tissues, causing bleeding, inflammation, and necrosis (tissue death) as they grow. This invasive quality of malignant neoplasms is reflected in the word origin cancer, from the Greek Karkinos, meaning CRAB. Cancer refers to the malignant neoplasm. Malignant cells from the primary tumor may travel via the blood stream or lymph to invade other tissues or organs and form a secondary tumor called a metastasis. This terms also refers to the destructive process. They very well may recur after surgical excision and other treatments. They vary in their degree of differentiation from the parent tissue. Highly differentiated cells try to mimic specialized functions from the parent tissue, but undifferentiated cancers, consisting of immature cells, have almost no resemblance to the parent tissue an so perform no useful function. They also rob the body of its energy and nutrition as they grow. They are the basis for many malignant neoplasms. The degree of differentiation of anaplastic cells is a consideration in the classification and staging of neoplasms.

Characteristics of Malignant Cells Loss of regulation of mitotic rate Loss of cell specialization Loss of contact inhibition Progressive acquisition of the cancerous phenotype & immortality Irreversibility of cancerous phenotype to greater aggressiveness Altered cell structure; diff in cell nucleus & cytoplasm Simplified metabolic activity Transplantability (metastasis) Ability to promote own survival L & B p. 278

How Cancer Invades Normal Tissue L & B p. 279 Fig 10-2 Fig. 09.05

Diagnostics X-ray imaging Computed Tomography Ultrasonography Magnetic Resonance Imaging Tissue Samples Screening: PSA L & B p. 284 Several procedures are used to diagnose cancer. However, only microscopic histologic examination can reveal the type of cell and its structural difference from the parent tissue. Tissue samples are obtained via Bx, Shedded cells (PAP), collections of secretions (sputum). Lymph nodes are also biopsied to see whether metastasis has begun. Simple screening measures can be done to pick up substances secreted by the tumor, such as prostatic-specific antigen (PSA) blood test now being used to identify early prostatic cancers. Increases in hormones or enzymes by normal tissues when theyare damaged may also contribute to the DX. One example of an enzyme increase is increased alkaline phoshatase noted in bone metastases and osteosarcoma. Recent research has identified tumor markers—which are used for early DX, tracking response to therapy, and for devising immunologic treatments. Some investigators studying chemical mediators of the immune systems have noted there seems to be communication between these mediators and the emotional centers of the brain. Therefore, they say that a person who states “I feel I have cancer” should be listened to, and the complaint investigated thoroughly.

Grading and Staging Grading Staging Amt of differentiation (level of functional maturity) of the cell Estimates rate of growth based on the mitotic rate Staging Use to classify solid tumors Refers to relative size of tumor and extent of disease TNM classification system L & B p. 284 Grading: cells that are most differentiated (most like the parent tissue and therefore least malignant) are classified as a GRADE 1 and are associated with a better prognosis. Grade 4 is reserved for the least differentiated and most aggressive malignant cells. Grading criteria may vary with different locations and types of tumors because of the differences inherent in tumor appearance and biologic behavior. TNM is an internationally agreed upon staging system: T stands for relative tumor size, depth of invasion, and surface spread. The N indicates presence and extent of lymph node involvement; M denotes the presence or absence of distant metastases. There are other systems used to differentiate types and locations of tumors—Table 10-6 shows the basic outline of the TNM system.

TNM Classification System Tumor To Tis T1, T2,T3,T4 No evidence of primary tumor Tumor in situ Ascending degrees of tumor size and involvment Nodes No N1a, N2a N1b, N2b, N3b Nx No abnormal regional nodes Regional nodes-no metastasis Regional lymph nodes-mets suspected; Regional nodes cannot be assessed clinically Metastasis Mo M1, M2, M3 No evidence of distant metastasis Ascending degrees of metastatic involvement of host including distant nodes

Effects of Cancer Disturbed or loss of physiologic functioning, from pressure to obstruction Hematologic Alterations: Impaired function of Blood Cells Infections: Fistula development & tumors may become necrotic; erode skin surface Hemorrhage: Tumor Erosion, bleeding, severe anemia Anorexia-Cachexia Syndrome: wasting away L & B Instructor Manual p. 84-85

Effects of Cancer Paraneoplastic Syndromes: ectopic sites w/excess hormone production Pain: major concern Physical Stress: body tries to respond and destroy neoplasm Psychological Stress

Surgical Tx Surgical Tx isused for Dx and staging of more than 90% of all cancers and for primary TXx of more than 60% of cancers If possible, tumor is removed in entirety; may necessitate mutilation of body Less distressing results Remove nonessential portion of organ or tissue containing tumor, such as in situ bowel tumors Remove organ whose function can be replaced chemically, such as thyroid Resect a pair of organs when the unaffected organ can take over the function of the missing one, such as a lung L & B p. 296