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Unit 4 Alterations in Cell Differentiation/Neoplasia UNIT 4 (OPTION) Alterations in Cell Differentiation/Neoplasia Originally developed by: Patricia Halliday RN, MN Former MN student and staff nurse in the Tom Baker Cancer Centre Outpatient Clinic Harry Plummer RN, MSc, MEd. PhD. Former Director of Nursing, Tom Baker Cancer Centre Revised (2000) by: Marlene Reimer RN, PhD, CCN(C) Professor, Faculty of Nursing, University of Calgary & Associate in Nursing, Calgary Health Region 1 Unit 4 Table of Contents Overview ..............................................................................................................4 Aim .................................................................................................................... 4 Objectives ......................................................................................................... 4 Resources .......................................................................................................... 4 Web Links......................................................................................................... 5 Section 1: Alterations in Cell Differentiation/Neoplasia ............................6 Learning Activity #1—Interpretations of Statistical Tables ..................... 6 The Cell Cycle .................................................................................................. 7 Alterations in Cell Differentiation ................................................................ 8 Learning Activity #2—Crossword Puzzles ................................................. 9 Final Thoughts...................................................................................................13 References ..........................................................................................................14 Glossary ..............................................................................................................14 Acronyms ............................................................................................................14 Checklist of Requirements..............................................................................15 Answers to Learning Activities ......................................................................16 Learning Activity #1—Interpretation of Statistical Tables ..................... 16 Learning Activity #2—Answers to Crossword Puzzles.......................... 16 Unit 4 Alterations in Cell Differentiation/Neoplasia 3 UNIT 4 Alterations in Cell Differentiation/Neoplasia Understanding the pathophysiology that occurs in the cancer patient’s body is the first step required in understanding the disease process of cancer. Knowledge of cancer pathophysiology provides the groundwork that is required for understanding both the current method of cancer treatment and the social/emotional impact of cancer on the client and family. To enhance your learning on cell differentiation/neoplasia, think of a cancer patient for whom you have cared. Try to recall the signs, symptoms, laboratory and radiological findings that your patient presented with and exhibited throughout the treatment. As you are working through this unit, try to provide the rationale for the physiological changes that could possibly account for your findings. 4 Unit 4 Alterations in Cell Differentiation/Neoplasia Overview Aim Upon completion of this unit you will be able to understand the nature of cancer from a physiological perspective. Cancer is a group of diseases, but the one constant is the importance of a defective growth mechanism which is characteristic of cancer cells. We have included information that spans both normal physiology and abnormal pathophysiology to aid your learning. Objectives Upon completion of this unit you will be able to: 1. Differentiate among the terms neoplasm, cancer and tumour. 2. Identify the main classes of neoplastic growth. 3. Differentiate between benign and malignant neoplasms as to structure, rate of growth, pattern of enlargement and spread. 4. Describe the possible cellular basis for formation of malignant neoplasms. 5. Define metastasis and describe methods by which it might occur. 6. Describe the principles for treating neoplastic conditions in relation to rationale for selection and effects on normal body functioning. Resources Requirements Porth, C. M. (2005).Pathophysiology – Concepts of Altered Health States (7th ed.). Philadelphia: Lippincott. Groenwald, Frogge, Goodman & Yarbro (2005 ) Invasion and mestastases (Ch. 4, pp. 59-69). Cancer Nursing (3rd ed.). Boston: Jones & Bartlett: Note: You do not need to buy this text for this course but if you intend to go into oncology nursing it is an excellent textbook. Porth covers the concepts we will be discussing in sufficient depth to understand the processes. Print Companion: Alterations in Cell Differentiation/Neoplasia Rankin, Reimer & Then. © 2000 revised edition. NURS 461 Pathophysiology, University of Calgary Unit 4 Alterations in Cell Differentiation/Neoplasia 5 Learning Activities Learning Activity #1—Interpretation of Statistical Tables Learning Activity #2—Crossword Puzzle #1 and #2 Supplemental Readings See US National Cancer Institute Website www.nci.nih.gov Leading causes of death and related cancer statistics are available from Statistics Canada www.statcan.ca/english/Pgdb/People/Health Web Links All web links in this unit can be accessed through the Web CT system. 6 Unit 4 Alterations in Cell Differentiation/Neoplasia Section 1: Alterations in Cell Differentiation/Neoplasia Learning Activity #1—Interpretations of Statistical Tables Use the following statistical tables, available from Statistics Canada and the National Cancer Institute of Canada to answer the following questions (answers at the end of this unit). Note also Figure 8-1 on page 156. 1. What is the leading cause of death in Canada for males and females? 2. What percentage of females currently aged 30 to 50 years have a lifetime probability of dying from some type of cancer? 3. Which types of cancer, once developed, are most likely to result in death, in both male and female adults according to 1999 statistics: 4. Which type of cancer had the highest incidence among adult males in the period 1990 to 2005? 5. Which type of cancer was most likely to cause death among adult males and females according to 2005 statistics? 6. What type of cancer continues to have the highest incidence among females? Rankin, Reimer & Then. © 2000 revised edition. NURS 461 Pathophysiology, University of Calgary Unit 4 Alterations in Cell Differentiation/Neoplasia 7 The Cell Cycle Note: all cells whether normal or abnormal proceed through the cell cycle growth rates tend to vary for both normal and malignant cells Figure 4.1 The Cell Cycle Adapted from Carter, S. K., Bakowski, M. T., & Hellmann, K. (1981). Chemotherapy of cancer (2nd ed.). Toronto: John Wiley & Sons. Please note Figure 8-2 on page 157 for another description of the cell cycle. The concept of the cell cycle has important ramifications in chemotherapy. Certain drugs are cell cycle specific or non cycle specific. You will notice in your clinical practice that certain chemotherapy drugs work in specific parts of the cell cycle and that patients often receive more than one drug in order to take advantage of cell cycling. 8 Unit 4 Alterations in Cell Differentiation/Neoplasia Alterations in Cell Differentiation Cell morphology/differentiation. Tumor classification and nomenclature (e.g. a cancer of connective tissue is called a sarcoma. What is a cancer of epithelial tissue and glandular tissue called?). Cell cycle - see Figure 4.1 in this unit and p. 157 Characteristics of: normal cells, cancer cells Tumor development Tumor cell markers Ectopic hormone production Metastasis Clinical manifestations Evaluation and treatment modalities Oncological emergencies After completing the readings, test your knowledge by completing the following Crossword Puzzles. Answers are at the back of this unit. Cell proliferation (pp.157-8). The vast majority of normal cells, which have a nucleus, will undergo proliferation. Please read cell differentiation on p.158 and make sure you understand what a stem cell is, and does, as it is an important concept in understanding carcinogenesis and potentially treatment. Page 159 – 161 compares and contrasts the differences between a benign and a malignant tumour. Can a benign tumour be fatal? Can you think of an example where this may be the case? Cancer cell characteristics (pp. 161-2). The term anaplasia means the tumour has no defining characteristics. In other words, you could not say the sample came from a particular tissue because it has none of the characteristics of any tissue (special ‘markers may be useful in trying to do this). Tumours are described as being well differentiated (meaning they closely resemble the tissue of origin), moderately differentiated, and poorly differentiated. Porth describes cell surface antigens on page 162. These antigens may be useful to indicate the presence of cancer although they do not have the specificity to use for screening. For example, carcinoembryonic antigen is usually elevated in colon cancer (and other conditions as Rankin, Reimer & Then. © 2000 revised edition. NURS 461 Pathophysiology, University of Calgary Unit 4 Alterations in Cell Differentiation/Neoplasia 9 well). The physician will measure the pre treatment level and the post treatment level (often 3-4 months after treatment). The level is then measured approximately twice a year. If the level stays down it is a fairly good indicator that the colon cancer is under control. If the level begins to rise it usually indicates a return of the cancer (of course, other reasons for the increase will need to be ruled out). Can you think of other tumour antigens that are used in this regard? Invasion and Metastasis (pp.162-3). Tumours may spread by local invasion, e.g. breast cancer may invade the chest wall. By seeding – for example, an ovarian cancersheds tumour cells into the peritoneal cavity. The final method is metastasis and is the most common form seen in clinical practice. Metastasis occurs more frequently by lymph spread than by the blood spread. It is hypothesized that blood is relatively toxic to cancer cells and the majority of cancer cells die in the bloodstream (although some will survive. It has been hypothesized that only 4% of cancer cells in the blood will survive). Tumour growth (Page 164) discusses the rate of growth in a normal and cancer cell. On a theoretical basis cancer cells have the potential to grow exponentially but rather they grow more or less in a Gompertzian manner. Cancer cells do die often because their blood supply has tortuous blood vessels which collapse quite easily and the development of a necrotic core. Etiology of Cancer (pp. 165-6). It is not an expectation for this course for you to know the molecular basis of carcinogenesis. Be aware,though, of growth promoting oncogenes and growth suppressing oncogenes. See figure 8-8 for a brief illustration of how they may be a cause of cancer. Porth also discusses the host and environmental factors for cacinogenesis on pp.167-170. These are ‘hot’ topics in research and the popular press. The role of the BRCA-1 and BRCA-2 gene mutations in cancer risk were probably the first to be used in evaluating ‘at risk’ families. Clinical Manifestations (PP. 171-73). No doubt many of you have seen the consequences of cancer as the disease progresses. Your text refers to tissue integrity and how this may manifested by bleeding; a sore that won’t heal; or pain. Some early signs of cancer may be dismissed as being ‘normal’. For example, bloating may be dismissed, but in fact, it may be an early warning for ovarian cancer. 10 Unit 4 Alterations in Cell Differentiation/Neoplasia Another example, is cachexia. As your text mentions there are probably a number of factors that contribute to it. Tumour necrosis factor was the first factor to be identified as a cause for cachexia followed by certain interleukins. The paraneoplastic syndrome also called inappropriate hormone production or ectopic hormone production is a fascinating biological phenomena. In effect, certain cancers will produce hormones or factors which are inappropriate for that particular tissue. This hormone, or factor production may have important clinical consequences. Please see Figure 8-3 on page 172 for a list of common paraneoplastic syndromes. Learning Activity #2—Crossword Puzzles Crossword #1 Clues: Across Down Rankin, Reimer & Then. © 2000 revised edition. NURS 461 Pathophysiology, University of Calgary Unit 4 Alterations in Cell Differentiation/Neoplasia 2. Cancer causing viruses 4. Evaluation of the tumor’s degree of malignancy 7. New growth of blood vessels to vascularize tissues 11. Increase in size of cell 12. A broad group of malignant neoplasms divided into two groups, carcinomas and sarcomas. 15. Lack of cell differentiation. 16. Conversion of one cell into another kind. 11 1. A spontaneous new growth of tissue forming an abnormal mass 3. Production of cancer 5. Can be elevated in persons with hepatic, pancreatic and embryonal carcinomas 6. Process by which a normal cell becomes a cancer cell 8. Many shapes, a variety of cell types 9. Process of classifying tumors 10. Increase in number of cells 13. Cancers of connective tissue 14. Not recurrent or progressive 12 Unit 4 Alterations in Cell Differentiation/Neoplasia Crossword #2 Clues: Across Down 1. To invade, grow 9. Cancers of epithelial tissue 11. Glial cells of the central nervous system 12. Substances produced by cancer cells found on tumor plasma membranes or in blood/urine 2. 3. 4. 5. Cancers of lymphatic tissue New, and abnormal formation of tissue Cancers of the blood-forming organs Causes an acceleration of the rate at which the cell has a chance of becoming malignant 6. Spread of cancer cells from a primary site of origin to a distant site 7. Antigens expressed by cells during certain stages of embryonic development 8. Process of cells dividing in an uncoordinated fashion, invading and destroying neighboring tissue 10. Development of cancer after exposure to the carcinogen Rankin, Reimer & Then. © 2000 revised edition. NURS 461 Pathophysiology, University of Calgary Unit 4 Alterations in Cell Differentiation/Neoplasia 13 Final Thoughts In this unit, we have tried to enhance your understanding of the key concepts that lead to changes in cell morphology in the human body, culminating in the complex pathological process of cancer. I have not attempted to provide an in-depth explanation of all cancers but rather provide you with some of the core knowledge so that you can research cancers you have an interest in. Porth does a very good job of explaining these core concepts. The word “cancer” still strikes fear into the hearts of people. In order to understand and appreciate the full extent of what is happening to the person with cancer, it is our belief that nurses must understand the underpinnings of the pathophysiology as well as the psychosocial processes involved. We have focused primarily on neoplasias in adults. However, it would be inappropriate to close this unit without some attention to differences in the types and mechanisms involved with children and older adults. Leukemia is the most common malignancy diagnosed in children under 15 years of age. Over 80% of leukemias in children are of the acute lymphoblastic (ALL) or acute undifferentiated (AUL) types . The article by Crawford and Cohen (1987) on “Relationship of cancer and aging” in Clinics in Geriatric Medicine, pp. 419-432, provides an indepth look at the interaction between cancer and aging. You may find it a bit technical, but might skim it for a general appreciation. If you had some difficulty understanding the stages of carcinogenesis you may find Figure 6 on p. 424 of this article a useful review. The Tom Baker Cancer Centre Library has an extensive collection of books, articles and audiovisual materials covering every aspect related to cancer. 14 Unit 4 Alterations in Cell Differentiation/Neoplasia References Crawford, J., & Cohen, H. (1987). Relationship of cancer and aging. Clinics in Geriatric Medicine, 3(3), 419-432. (3rd Groenwald, Frogge, Goodman, & Yarbro (1993). Cancer nursing ed.). Boston: Jones & Bartlett. Porth, C. M. (2205). Pathophysiology- Concepts of Altered Health States (7th ed.). Philadelphia: Lippincott. Glossary No separate glossary is provided in this unit but you are encouraged to review the answers to the crossword puzzles to check your grasp of terminology. Acronyms ALL acute lymphoblastic leukemia AUL acute undifferentiated leukemia DNA deoxyribonucleic acid RNA ribonucleic acid Rankin, Reimer & Then. © 2000 revised edition. NURS 461 Pathophysiology, University of Calgary Unit 4 Alterations in Cell Differentiation/Neoplasia Checklist of Requirements Porth (2005) Chapter 8 Groenwold, Frogge, Goodman & Yarbro (2005) Invasion and metastases Ectopic hormone production Print Companion Alterations in Cell Differentiation/Neoplasia Learning Activities Learning Activity #1—Interpretation of Statistical Tables Learning Activity #2—Crossword Puzzles #1 and #2 15 16 Unit 4 Alterations in Cell Differentiation/Neoplasia Answers to Learning Activities Learning Activity #1—Interpretation of Statistical Tables 1. 2. 3. 4. 5. 6. cancer 22.8% lung pancreas leukemia stomach cancer of the prostate cancer of the lung cancer of the breast Learning Activity #2—Answers to Crossword Puzzles Crossword #1 Word List A-fetoprotein angiogenesis anaplasia benign cancer carcinogenesis grading hypertrophy hyperplasia metaplasia oncogenic viruses pleomorphism sarcomas staging transformation tumor Crossword #2 Word List carcinomas gliomas initiation leukemias lymphomas malignant metastasis neoplasm oncofetal promotion progression tumor cell markers Rankin, Reimer & Then. © 2000 revised edition. NURS 461 Pathophysiology, University of Calgary