NR283 Ch.20

Diagnostic Tests

1.Blood tests are important both as an indicator of a problem and in monitoring the effects of chemotherapy and radiation. Hemoglobin and erythrocyte counts may be low, a general sign of cancer. In some types of cancer, such as leukemia, the cell characteristics are diagnostic when confirmed by a bone marrow examination. 2.Tumor markers are substances, enzymes, antigens, or hormones, produced by some neoplastic cells. These tumor cell markers can be used to screen high-risk individuals, confirm a diagnosis, or monitor the clinical course of a malignancy. Examples include carcinoembryonic antigen for colon cancer, human chorionic gonadotropin for testicular cancer, alpha-fetoprotein for hepatocellular cancer, CA125 for ovarian cancer, and prostate specific antigen for prostate cancer. 3.X-ray, ultrasound, magnetic resonance imaging and computed tomography (CT) scans are methods of examining changes in tissues or organs (see Ready Reference 5 for information on these tests). In some cases radioisotopes may be used during these procedures to trace metabolic pathways and assess function. 4.Cytologic tests are used to screen high-risk individuals, confirm a diagnosis, or follow a clinical course and monitor change. Histologic and cytologic examinations are used to evaluate biopsies of suspicious masses and check sloughed cells in specific tissues (exfoliative cytology). This is the only dependable confirmation of malignancy. An accurate evaluation depends on good technique and preservation of the specimen.

Prognosis

A "cure" for cancer is generally defined as a 5-year survival without recurrence after diagnosis and treatment. In some cases, several periods of remission (no clinical signs) may occur before the disease becomes terminal. In some cases, early diagnosis and treatment limit the extent of the illness in an individual. In other cases, cancer treatment involves a prolonged period of illness with intermittent acute episodes. Information and support for the patient and family are offered by the American Cancer Society as well as cancer clinics and the many other community support groups.

Malignant Tumors: Cancer Pathophysiology

A tumor manifests as an enlarging space-occupying mass composed of more primitive or dysplastic cells. Normal organization, growth inhibition, contact controls, and cell-cell communication are absent. Cell membranes, including surface antigens, are altered. The expanding mass compresses nearby blood vessels, leading to necrosis and an area of inflammation around the tumor, and increases pressure on surrounding structures. Malignant cells do not adhere to each other but often break loose from the mass, infiltrating into adjacent tissue. Tumor cells often secrete enzymes such as collagenase, which break down protein or cells, adding to the destruction and facilitating the tumor's spread into adjacent tissue. Inflammation and the loss of normal cells lead to a progressive reduction in organ function. As a tumor mass enlarges, the inner cells are frequently deprived of blood and nutrients and die. This necrosis can lead to more inflammation and infection at the site. Some cancer cells secrete growth factors, which stimulate angiogenesis, the development of new capillaries in the tumor, thus promoting tumor development. Grading of tumors is based on the degree of differentiation of the malignant cells—a grade I tumor has well-differentiated cells similar to the original cells, whereas a grade IV tumor is undifferentiated with cells varying in size and shape (anaplasia); this type of tumor is considered highly malignant and likely to progress quickly.

Treatment

Basic treatment measures are surgery, chemotherapy, immunotherapy, or radiation, or a combination thereof, depending on the specific cancer. Not all cancer cells are sensitive to radiation or chemotherapy. Hematopoietic cancers such as leukemia are treated by chemotherapy because the cancer cells are dispersed in the blood. Treatment may be: •Curative if the tumor is small and localized, or •Palliative if the cancer is advanced. Palliative treatment is intended to reduce the manifestations and complications related to the cancer and to prolong life. For example decreasing the size of a tumor may lessen the pressure on a nerve, relieving pain, or reduce pressure on the esophagus or bronchus. Adjuvant therapy is additional prophylactic (preventative) treatment used in cancers that are known to metastasize early in their development, producing secondary tumors that are too small to be detected (micrometastases). Chemotherapy and radiation therapy are administered in repeated doses at intervals that maximize tumor cell death but minimize the effects on normal tissues. Not all cancer cells are destroyed in one treatment.

Cancer Incidences

Cancer among men: •Three most common •Prostate Cancer—First among men of all races •Lung Cancer—Second among white, black, native American, and Asian men; third among Hispanic men •Colorectal cancer—Second among Hispanic; third among white, black, native American, and Asian men •Leading causes of cancer deaths •Lung cancer—First among men of all races •Prostate cancer—Second among white, black, Hispanic, and native America men; fourth among Asian men •Liver cancer—Second among Asian men •Colorectal cancer—Third among men of all races Cancer among women: •Three most common •Breast cancer—First among women of all races •Lung cancer—Second among white, black and native American women; third among Asian and Hispanic women •Colorectal cancer—Second among Asian and Hispanic women; third among white, black and native American women •Leading causes of cancer deaths •Lung cancer—First among white, black, Asian, and native American women; second among Hispanics •Breast cancer—First among Hispanic women and second among white, black, Asian, and native American women •Colorectal cancer—Third among women of all races

Host Defenses

Cancer suppressor genes present in the body can inhibit neoplastic growth. The immune system appears to offer protection by reacting to changes in the membranes of some tumor cells, which are seen as "foreign." The immune response includes both cell-mediated and humoral immunity (see Chapter 7). Cytotoxic T lymphocytes, natural killer cells, and macrophages are involved in immune surveillance and the destruction of "foreign" or abnormal cells. Temporary or long-term immunodeficiency has been shown to increase the risk of cancer.

Etiology Carcinogenesis

Carcinogenesis is the process by which normal cells are transformed into cancer cells. Malignant tumors develop from a sequence of changes over a relatively long period of time. A combination of factors or repeated exposure to a single risk factor leads to changes that activate or change gene expression, leading to transformation of the normal cell into a malignant cell. Some specific cancers have well-established risk factors (e.g., bronchogenic carcinoma or lung cancer and cigarette smoking). The multiplicity of developmental steps in carcinogenesis is supported by the fact that not all cigarette smokers develop cancer. The stages in carcinogenesis have been organized into: 1.Initiating factors or procarcinogens cause the first irreversible changes in the cell DNA. Genetic changes or exposure to an environmental risk may cause this first mutation (Fig. 20-8). This initial change does not create an active neoplasm. 2.Exposure to promoters later causes further changes in DNA, resulting in less differentiation and an increased rate of mitosis. Dysplasia or anaplasia may be evident at this time. This process may lead to development of the tumor. Promoters include hormones and environmental chemicals. The prolonged time interval and multiple factors involved complicate efforts by researchers to establish risk factors for many cancers. 3.Continued exposure and changes in DNA result in a malignant tumor that is capable of growth and invasion of local tissue. 4.Changes in the regulation of growth result in cells that are capable of detaching from the tumor and spreading to distant sites (metastasis).

Characteristics of Benign and Malignant Tumors

Characteristics of specific tumors vary considerably depending on the cell of origin. The general characteristics of each type are summarized in Table 20-2. Benign tumors usually consist of differentiated cells that reproduce at a higher than normal rate. The benign tumor is often encapsulated and expands but does not spread (Fig. 20-1). It is usually freely moveable on palpation. Tissue damage results from compression of adjacent structures such as blood vessels. A benign tumor is not considered life threatening unless it is in an area such as the brain where the pressure effects can become critical. By comparison, malignant tumors are usually made up of undifferentiated, nonfunctional cells that do not appear organized. The cells tend to reproduce more rapidly than normal and often show abnormal mitotic figures. These cells have lost cellular connections with each other, and reproduction is not inhibited in the presence of other similar cells. Tumor cells infiltrate or spread into surrounding tissue and may easily metastasize or break away to spread to other organs and tissues

Review of Normal Cells

Every cell has an outer plasma membrane, enclosing the fluid cytoplasm or intracellular fluid. The membrane is semipermeable, controlling passage of materials into and out of the cell. It also maintains the cell's shape. The nucleus of the cell consists of DNA, the genetic material that controls the particular cell's function and structure, enclosed in the nuclear membrane. The cytoplasm contains various nutrients, proteins, glucose, and electrolytes required for cell metabolism. Other structures are located in the cytoplasm, such as ribosomes, granules that produce proteins; mitochondria providing energy in the form of ATP for cell activities; lysosomes containing digestive enzymes, to break down unwanted materials; and the Golgi complex to process and release proteins. Regulator genes control mitosis for different types of cells. Growth factors such as cytokines signal proliferation, whereas inhibitors inside cells prevent excessive growth. During its lifespan, each cell follows the basic cell cycle of growth and reproduction or mitosis. Different cells experience different life spans; for example, erythrocytes live for approximately 120 days, but some leukocytes survive only a few days. Highly specialized cells such as neurons cannot undergo mitosis, but they have a long life span of many years. Epithelial cells usually replicate very rapidly because of the demand for replacement caused by constant "wear and tear" on surface tissues. There are usually several layers of tightly packed cells, the upper layers being sloughed off or shed and replaced by regenerating cells from the lower layers. Changes in DNA can alter cell structure and function or cause cell death. DNA can mutate spontaneously during mitosis or as a result of exposure to chemicals, viruses, radiation, and other environmental hazards. Rapid rates of mitosis associated with tissue trauma or other stimuli may increase the risk of errors occurring in the chromosomes, cell enzymes, or cell components.

Other Drugs

Hormones are frequently prescribed during cancer treatment in addition to the basic treatment. A glucocorticoid such as prednisone is used to decrease mitosis and increase erythrocyte counts (see Chapter 5). For the patient, these drugs improve appetite and a sense of well-being. They also decrease inflammation and swelling around the tumor. Sex hormones are beneficial when tumor growth is dependent on such hormones; for example, estrogens may slow the growth of prostate cancer. Hormone-blocking agents are often effective in reducing tumors and preventing recurrences. Tamoxifen is an example of an estrogen-blocking agent used in clients with estrogen-dependent breast cancer; it has been particularly useful in postmenopausal women. Biologic response modifiers are agents that augment the natural immune response in the body to improve surveillance and removal of abnormal cells. Included in this group are a natural product of human cells, interferon, and bacillus Calmette-Guérin (BCG) vaccine (for tuberculosis). Interferon has not been as effective as expected, primarily due to undesirable and often dangerous side effects such as negative effects on areas of the immune system, but investigation into this area continues. The BCG vaccine may be injected near the tumor or instilled in a cavity such as the bladder when cancer is present. It stimulates the movement of macrophages and T lymphocytes to the site, where they may destroy the tumor cell. Other than BCG for treatment of bladder cancer, these are not a first-line treatment at this time. Another focus for investigation is the angiogenesis inhibitor drug group (e.g., angiostatin or endostatin). Angiogenesis means new blood vessels, and as a tumor grows and spreads, so must new blood vessels. Anti-angiogenesis drugs block the stimulus for endothelial cell (blood vessel walls) growth by various mechanisms and therefore reduce local blood flow and starve the tumor cells. It was hoped that these drugs would have fewer adverse effects and could be combined with traditional chemotherapy for more effective treatment. Analgesics for pain control are an important part of therapy, particularly when cancer is advanced (see Chapter 4). Determining the cause of the pain is important because this determines the therapeutic approach. In some cases, a specific factor such as infection or muscle spasm can be treated, leading to pain reduction. Radiation treatment can relieve nerve compression.

Complementary Therapies

Many alternative approaches are used to treat or "cure" cancer. These nonmedical therapies are referred to as complementary. They range from the use of a raw food macrobiotic diet, to the use of insulin and glucose to accompany chemotherapy. Although some complementary therapies have shown benefit when combined with medical therapy, there is no research-based evidence to show that any complementary therapy on its own will prolong life or reduce metastasis.

Nutrition

Patients with advanced cancer are often malnourished. Contributing factors include change in taste sensations, anorexia and vomiting, sore mouth or loss of teeth, pain and fatigue, malabsorption due to inflammation in the digestive tract, altered metabolism, and nutrient trapping by the tumor. These factors may result from the tumor itself or from the effects of chemotherapy and radiation. The use of measures such as ice and mouth rinses is suggested to reduce the discomfort of ulcers and inflammation in the mouth. Frequent small amounts of nonirritating and favorite foods are better tolerated.

Radiation Therapy

Radiation may be used alone (e.g., for some lymphomas) or combined with other therapies to treat radiosensitive tumors. Radiotherapy causes mutations or alterations in the targeted DNA, thus preventing mitosis or causing immediate cell death. Radiation also damages blood vessels, cutting off blood supply to the tumor cells. There are several methods of administration: •External sources, such as a cobalt machine, deliver radiation for a short period of time to a specific site in the body. •Internal insertion of radioactive materials at the tumor site may be used to treat specific cancers such as cervical or oral tumors. This is accomplished by sealing the radioisotope (e.g., radium) in a "seed" or needle and implanting the device at the site (brachytherapy). •Another method is to instill a radioisotope in a solution in a body cavity, such as the pleural cavity, to control excessive inflammatory exudate or blood from the tumor. Precautions are required when clients have internal sources of radiation to minimize radiation exposure of other persons. Adverse effects of radiation depend on the dose and extent of penetration of radiation into the body. Normal cells that rapidly reproduce, such as those in the skin and mucosa (epithelial cells), bone marrow, and gonads are also damaged by radiation. 1.Bone marrow depression is the most serious negative effect, so blood cell counts are constantly monitored. Decreased leukocytes greatly increase the risk of infection, decreased platelets may cause excessive bleeding, and decreased erythrocytes contribute to fatigue and tissue breakdown. 2.Epithelial cell damage includes damage to blood vessels (vasculitis) and skin. Skin becomes inflamed (as in a sunburn), and hair loss (alopecia) occurs. The mucosa of the digestive tract is damaged, resulting in some nausea, vomiting, and diarrhea, and the attendant risk of malnutrition and dehydration. 3.Abdominal radiation is likely to damage the ovaries or testes, leading to sterility or the risk of teratogenesis. Sperm banking or egg retrieval and storage should be discussed with the client before starting treatment. 4.In addition, radiation often produces a nonspecific fatigue and lethargy accompanied by mental depression.

Examples of Malignant Tumors

Skin Cancer Skin cancer is visible, easily diagnosed and treated (by surgery), and develops slowly; therefore most types with the exception of malignant melanoma have an excellent prognosis. Skin cancers have the highest rate of recurrence and usually arise on the head and neck or back, areas exposed to the sun and irritation. They occur more frequently in individuals with fair skin who are over 40 years of age and live in southern climates. The number of cases is increasing, resulting in a public education campaign to reduce sun exposure and sun tanning practices. Basal cell carcinoma is the most common form of skin cancer (see Chapter 8 for other skin cancers). The tumor appears as a pearly papule and develops a central ulceration, a "rodent ulcer" Ovarian Cancer Ovarian cancer has a very poor prognosis, ranking high in mortality rates. The tumor is hidden in the peritoneal cavity; it is a "silent" tumor (see Fig. 20-7). Although there are many histologic types of ovarian cancer, this section deals only with the basic concepts (see Chapter 19). Hormonal and genetic factors appear to play a role in development of this cancer. Presenting (or first) signs are vague and appear only after the tumor is well advanced and is large enough to cause pressure on the adjacent structures, such as the bladder or intestine, or when an inflammatory exudate forms in the abdominal cavity. These late signs often contribute to a late diagnosis and a delay in treatment. There are tumor markers to assist in early diagnosis and screening, but false-negatives do occur. The marker CA125 is elevated in other conditions as well as ovarian cancer, but is useful in monitoring the effectiveness of treatment. The first indications are usually altered bowel or bladder function or increased abdominal girth. Brain Cancer Brain tumors may be benign or malignant. Both are space-occupying masses that create pressure inside the skull, and both are serious for this reason. Brain tumors, even when small, can cause death if they are located in the brainstem or cerebellum, where they can interfere with vital functions such as respiration. Removal of the mass may be fairly easy if it is located on the brain surface but difficult and dangerous if it is located elsewhere (Fig. 20-12). Brain tumors vary histologically, originating from neurons, neuroglial cells, blood vessels, or connective tissue. They can occur in children as well as adults.

Risk Factors and Prevention

Some risk factors such as foods can be avoided. Other factors, such as genetic predisposition, cannot be avoided but can be addressed by encouraging frequent screening and therefore early diagnosis. For example, increasing fiber content in the diet and reducing fats decreases the risk of breast cancer. Deeply pigmented fresh fruits and vegetables provide antioxidants such as vitamins A and E, chemicals that protect cells against damaging substances called free radicals. Free radicals form in cells from exposure to radiation or certain products from metabolic processes. Foods containing antioxidants are now promoted to offset this problem.

Chemotherapy

Some types of cancer cells respond well to certain antineoplastic drugs, whereas other types of cells are resistant to this therapy. Chemotherapy may be used alone (as in leukemias), or may be combined with surgery or radiation. Usually therapy commences approximately 6 weeks following surgery, allowing time for some recovery. In most treatment protocols, a combination of two to four drugs, each from a different classification, is given to a patient at periodic intervals. The classifications include antimitotics, antimetabolites, alkylating agents, and antibiotics. The drugs interfere with protein synthesis and DNA replication at different points in the tumor cell cycle, thus destroying the cells. illustrates the combination of: •Adriamycin (doxorubicin), an antitumor antibiotic that binds DNA and inhibits synthesis of nucleic acids, acting primarily on cells in the S phase (DNA synthesis) but with some activity in other stages (e.g., altering the cell membrane) •Bleomycin, also an antitumor antibiotic that inhibits DNA synthesis •Vinblastine, a cell-cycle-specific antimitotic drug that acts on cells in the M stage (mitosis) •Dacarbazine, an alkylating agent nonspecific drug acting at several points in the cycle This combination is the "ABVD" regimen for treating Hodgkin's lymphoma, still the most effective drug treatment for this cancer, although many other combinations have been tried. This combination of drugs is administered intravenously on day 1 and day 15, and then repeated every 4 weeks. Every 4 weeks, Hydrocortisone may be added to the combination of drugs. Adverse effects (side effects) may be quite marked with drug therapy. As with radiation, the normal cells are also damaged, most commonly the skin and mucosa, bone marrow, and gonads. The need to minimize adverse effects is another factor in choosing the combination. Bone marrow depression is the limiting factor with chemotherapy, and dangerously low blood counts may require transfusions or cessation of therapy until the bone marrow recovers. Blood tests are taken before each treatment to check cell count. The nadir, or point of lowest cell count (neutropenia or leukopenia), may occur at different points in the cycle depending on the particular drug. If the count is too low, treatment may need to be postponed, and antibiotics or hospitalization may be required. Hemorrhage is a major risk with thrombocytopenia. •Vomiting may occur during or shortly after treatment owing to direct chemical stimulation by the drug of the emetic or vomiting center in the brain. Vomiting may continue after treatment in response to the mucosal inflammation and damage in the digestive tract. •Epithelial cells are easily damaged because of the ongoing mitosis. Hair loss (alopecia) and breakdown of skin and mucosa occur frequently. Stomatitis in the mouth and diarrhea are common problems and contribute to malnutrition. Candidal infections are common in the mouth. •In addition, some antineoplastic drugs have unique damaging effects in specific areas; for example, fibrosis in the lungs or damage to myocardial cells.

Staging of Cancer

Staging of cancer is a classification process applied to a specific malignant tumor at the time of diagnosis. It may be repeated at critical points. The staging system describes the extent of the disease at the time and therefore provides a basis for treatment and prognosis. Staging systems are based on the: •Size of the primary tumor (T) •Extent of involvement of regional lymph nodes (N) •Spread (invasion or metastasis) of the tumor (M)

Surgery

Surgery involves the removal of the tumor and surrounding tissue, including the nearby lymph nodes if required. The tumor cells and the boundaries are checked to confirm the diagnosis and to ensure their complete removal. The surgical approach may involve the use of a laparoscope and several small incisions. An alternative to surgery for small single tumors in the lungs or liver is radiofrequency ablation. This process is less invasive, easier for the patient to tolerate, and does not require the loss of an entire lobe of the organ as may happen with surgery.

Nomenclature

Tumors are named according to a system (Table 20-1). The root word, such as chondro, is the cell of origin, in this case cartilage. Depending on the type of tissue in which a tumor is located, the suffix indicates malignant tumors (carcinoma for epithelial tissue, sarcoma for connective tissue). The suffix oma alone indicates a benign tumor, e.g., lipoma. However, a number of neoplastic disorders have acquired unique names that are recognized in medical practice. Examples include Hodgkin disease, Wilms tumor, and leukemia. Oncology is the study of malignant tumors, otherwise known as cancer.

Spread of Malignant Tumors

Tumors spread by one or more methods depending on the characteristics of the specific tumor cells. They produce secondary tumors that consist of cells identical to the primary (parent) tumor. Many cancers have spread prior to diagnosis, and this factor must be considered before treatment begins. There are three basic mechanisms for the spread of cancer: •Invasion refers to local spread, in which the tumor cells grow into adjacent tissue and destroy normal cells (Fig. 20-4). Tumor cells are loosely attached to other cells and also secrete lytic enzymes that break down tissue. •Metastasis means spread to distant sites by blood or lymphatic channels. In this case the tumor cells erode into a vein or lymphatic vessel, travel through the body, and eventually lodge in a hospitable environment to reproduce and create one or more secondary tumors. •Seeding refers to the spread of cancer cells in body fluids or along membranes, usually in body cavities. Again, the tumor cells break away and travel easily with the movement of fluid and tissue.

Effects of Malignant Tumors All health care workers should be aware of the early indicators of possible malignancies. The classic warning signs of cancer are listed in the box below.

Warning Signs of Cancer 1. Unusual bleeding or discharge anywhere in the body. 2. Change in bowel or bladder habits (e.g., prolonged diarrhea or discomfort). 3. A change in a wart or mole (i.e., color, size, or shape). 4. A sore that does not heal (on the skin or in the mouth, anywhere). 5. Unexplained weight loss. 6. Anemia or low hemoglobin, and persistent fatigue. 7. Persistent cough or hoarseness without reason. 8. A solid lump, often painless, in the breast or testes or anywhere on the body.

Anemia

a decrease in circulating hemoglobin and oxygen-carrying capacity in the blood because of decreased erythrocyte production, decreased hemoglobin production, excessive hemolysis, or loss of blood.

Leukopenia

a decreased number of leukocytes in the blood.

Mitosis

a process of cell reproduction resulting in two daughter cells with the same DNA as the parent cell.

Radioisotope

a radioactive form of an element, giving off radiation (beta or gamma) in the body, used in diagnosis and therapy.

Antineoplastic

a substance or process that destroys neoplastic cells.

Thrombocytopenia

abnormally low number of thrombocytes or platelets.

Differentiation

increased specialization of cells for certain functions.

Chromosome

made up of genes, the genetic code of the living cell, consisting of DNA.

Apoptosis

normal programmed cell death in tissues.

Palliative

providing comfort and relieving pain and other symptoms of a disease without effecting a cure.

Metastasis

spread of cancer cells to distant sites by the blood or lymphatics; secondary malignant tumor.

Angiogenesis

the development of new capillaries.

Prognosis

the probable outcome of a disease.

Atypical

unusual, not characteristic.

Local Effects of Tumors

• Pain is not usually an early symptom of cancer; rather, it occurs when the tumor is well advanced. Pain is a warning of a problem; therefore it is helpful if it occurs early, but this is rare. The severity of the pain depends on the type of tumor and its location. Pain may be caused by direct pressure of the mass on sensory nerves, particularly where space is restricted (e.g., bone cancer). Secondary causes of pain include infection, ischemia, and bleeding. Blood can be "irritating" to tissues and, if it collects in an area, can cause pressure on nerves. • Obstruction can result when a tumor compresses a duct or passageway from an external position or grows inside a passageway or around a structure (Fig. 20-3). Obstruction may occur in ducts or tubes in the body such as those in the digestive tract. Blood supply or lymphatic flow may be restricted, leading to ulceration and edema. Air flow in the bronchi or nerve conduction may be blocked. Obstructions can cause serious complications for the patient, even in the early stage. In the late stage prevention of obstruction may form the rationale for continuing palliative treatment. • Tissue necrosis and ulceration may lead to infection around the tumor, particularly in areas where normal flora can become opportunistic. For example, infection is likely to be associated with cancer in the oral cavity. Host resistance to microbial invasion is often reduced with cancer.

Systemic Effects of Malignant Tumors

•Weight loss and cachexia (severe tissue wasting) occur with many malignancies. •Anemia or decreased hemoglobin is a common problem resulting from anorexia and decreased food intake, chronic bleeding with iron loss, and bone marrow depression. •Severe fatigue caused by inflammatory changes, cachexia, anemia, stress, and treatment schedules. •Infections such as pneumonia occur frequently as host resistance declines. Tissue breakdown develops and the immune system is less effective. •Bleeding may occur because the tumor cells may erode the blood vessels or cause tissue ulceration. Bone marrow depression and hypoproteinemia may contribute to poor clotting. Chronic bleeding is common in the digestive tract, where the mucosa fails to regenerate quickly. Chronic blood loss leads to iron deficiency anemia. •Paraneoplastic syndromes are additional problems associated with certain tumors, such as bronchogenic carcinoma in the lungs. Tumor cells release substances that affect neurologic function or blood clotting or have hormonal effects.