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Which part of the colon runs down the left side of the abdomen?
Colorectal cancer can originate only in the rectum.
False
What are the four layers of the large intestine wall?
Serosa, muscular layer, submucosa, mucosa
Mutation in the __________ genes can lead to the development of colorectal cancer.
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Which of the following is NOT a modifiable risk factor for colorectal cancer?
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Match the following parts of the colon with their descriptions:
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Colonic crypts are formed by the mucosa layer of the large intestine.
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Name two nonmodifiable risk factors for colorectal cancer.
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The __________ layer of the large intestine consists of a dense layer of tissue that contains blood vessels, lymphatics, and nerves.
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Which gene mutations may further develop from early adenomas into colon cancer?
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What is the percentage of cancer cases occurring in people aged 60 and above in Australia?
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Cancer mortality rates have increased in both Australia and New Zealand over the last few decades.
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What is the primary factor driving the increase in cancer incidence over the past 20 years in Australia?
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The most common cancer diagnosed in Australia is __________.
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Match the following countries with their cancer statistics:
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In which year did the age-standardised incidence rate of all cancers combined reach its peak in Australia?
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What characterizes cancer cells in contrast to normal cells?
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Normal cells do not divide unless there is surrounding cell degeneration or a physiological need for more cells.
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Name the two types of genes impacted by mutations that are crucial in the development of cancer.
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The process of cancer development includes three stages: initiation, promotion, and __________.
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Match the following terms with their definitions:
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What effect does contact inhibition have on normal cells?
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Mutations in tumor suppressor genes can make them inactive, leading to an increased risk of cancer.
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What is the term for the time required for a tumor mass to double in size?
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Which site is most commonly associated with the metastasis of colon cancer?
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Tumour angiogenesis is the process by which a tumour develops its own blood supply.
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What is the role of the sentinel lymph node in cancer metastasis?
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The immune system can distinguish normal cells from _____ cells.
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Match the immune cells with their primary functions in tumor immunity:
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What must tumour cells do to successfully metastasize?
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What percentage of cancers or predispositions to cancer are inherited from one’s parents?
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Acquired mutations are not passed on to daughter cells during cell division.
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Name a type of cancer that has been linked to UV radiation exposure.
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One example of a chemical carcinogen is __________.
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Match the following carcinogens with their associated cancers:
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Which of the following agents can initiate and promote cancer development?
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The process of developing cancer can take years or even decades.
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What term is used to describe the time between the first genetic alteration and the clinical evidence of cancer?
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Carcinogens may be chemical, radioactive, or __________ in nature.
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Which lifestyle change can help reduce the chance of cancer development?
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What was the estimated number of new invasive carcinoma cases diagnosed in Australia in 2021?
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The incidence of cancer in females is higher than in males.
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What are the three stages involved in the process of cancer development?
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The generation time of a cell is the time from when a cell enters the cell cycle to when it divides into two identical __________.
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Match the following cancer types with their common characteristics:
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What is the role of proto-oncogenes in normal cell processes?
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Normal cells can divide indiscriminately in the absence of physiological needs.
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What term is used to describe the process by which cancer cells grow continuously and indiscriminately?
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Tumour suppressor genes function to regulate cell growth by preventing cells from going through the cell cycle. Examples include __________ and __________.
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Match the following terms with their definitions:
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Which of the following statements about carcinogens is true?
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Inherited mutations account for a significant proportion of all cancer cases.
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Name one type of cancer associated with UV radiation exposure.
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A tumor that is 1.0 cm contains approximately __________ cancer cells.
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Match the following types of carcinogens with their examples:
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Which site is most commonly associated with the metastasis of colon cancer?
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Tumour cells can evade detection by the immune system through altered cell-surface antigens.
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What is the term for the process in which a tumour develops its own blood supply?
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The first lymph node encountered by travelling tumour cells is known as the __________ lymph node.
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Match the following immune cells with their primary functions in tumor immunity:
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What is the main difference between benign and malignant tumors?
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Oncofetal antigens have diagnostic value exclusively for malignant tumors.
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What cytokine is produced by macrophages that stimulates T-lymphocyte activation?
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The _____ is a type of tumor antigen often found in both fetal and cancerous cells.
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Match the following tumor markers with their associated cancers:
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Which of the following is NOT a mechanism by which cancer cells evade the immune system?
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Cytokines secreted by macrophages have no impact on tumor cells.
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What factor primarily determines whether a tumor is categorized as benign or malignant?
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The immune system can recognize cancer cells via specific tumor-associated _____.
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Which cells are primarily responsible for producing specific antibodies that can target tumor cells?
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What is the primary goal of surgical therapy in cancer treatment when a cure is not possible?
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Surgical procedures can be utilized for both preventive measures and to improve the effectiveness of chemotherapy.
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Name one surgical procedure used for the cure or control of cancer.
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Prophylactic surgery involves the removal of __________ organs to reduce cancer risk.
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Which of the following is a goal of debulking surgery?
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Match the following surgical terms with their definitions:
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Which patients might benefit from prophylactic mastectomy?
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Surgery remains the only form of treatment for cancer.
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What is the primary purpose of intravesical bladder chemotherapy?
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Chemotherapy selectively destroys only cancer cells, sparing normal cells.
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What is a common acute side effect of chemotherapy treatment?
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Radiation therapy uses high-energy beams or waves to produce _____ in the cells.
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Match the following chemotherapy effects with their categories:
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What is a primary goal of chemotherapy?
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Alkylating agents are considered cell cycle phase specific.
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Name one effect of chemotherapy medications on cancer cells.
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Mitotic inhibitors act during the _____ phase to prevent cell division.
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Match the chemotherapy medication categories with their characteristics:
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What surgical procedure may be performed to relieve bowel obstruction due to metastatic cancer?
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Cell cycle phase specific medications are effective only during certain phases of the cell cycle.
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When do most chemotherapy agents exert their maximum efficacy?
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The primary mechanism of action for antitumor antibiotics is to bind directly to _____ and inhibit DNA synthesis.
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Which of the following categories of chemotherapy is considered cell cycle phase non-specific?
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What is the most common route for administering chemotherapy?
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Irritants and vesicants are the same in terms of their potential tissue damage during chemotherapy administration.
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What type of chemotherapy administration delivers drugs directly to the body cavity, such as the peritoneum?
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Chemotherapy can be administered via __________ access device to mitigate risks associated with IV administration.
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Match the following chemotherapy administration methods with their corresponding examples:
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Which of the following methods involves delivering chemotherapy to the tumor site directly through the arteries?
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Safe handling guidelines for chemotherapy are established to protect only the patients from exposure.
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What device is used to reduce the need for repeated lumbar punctures in intrathecal chemotherapy?
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After chemotherapy is administered intraperitoneally, the fluid is generally allowed to 'dwell' in the peritoneum for __________ hours.
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Which of the following describes the primary benefit of regional chemotherapy administration?
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Study Notes
Colorectal Cancer
- Colorectal cancer is a malignant tumor originating in the colon or rectum.
- The colon consists of four parts:
- Ascending colon: Right side of abdomen
- Transverse colon: Across the upper abdomen
- Descending colon: Left side of abdomen
- Sigmoid colon: S-shaped connection to rectum
Large Intestine Wall Layers
- Serosa or adventitia: Outermost layer
- Muscular layer: Contracts to move food through the bowel
- Submucosa: Dense layer containing blood vessels, lymphatics, and nerves
- Mucosa: Innermost layer composed of simple columnar epithelium with goblet cells
- Forms invaginations called colonic crypts or glands
Colorectal Cancer Development
- Occurs when epithelial cells mutate in the APC genes (tumor suppressor genes)
- This leads to the formation of early adenomas (small polyps)
- Further mutations can occur in genes like KRAS or p53
- Contribute to the development of colon cancer
Risk Factors
-
Modifiable:
- Smoking
- Obesity
- Processed meat-rich diet
- Excessive alcohol intake
-
Nonmodifiable:
- Age above 40
- Family history of colorectal cancer or polyps
- Hyperinsulinemia
- Inflammatory bowel disease (Crohn's disease, ulcerative colitis)
Cancer: An Overview
- Cancer is a group of diseases characterized by uncontrolled and unregulated cell growth.
- While often associated with aging, cancer can occur at any age.
- In Australia, cancer incidence has increased by 67% in the past 20 years, mainly due to an aging population.
- However, the age-standardized incidence rate of all cancers combined has decreased from a peak in 2008 to an estimated rate in 2021.
- The most common cancers diagnosed in Australia are breast, prostate, melanoma of the skin, colorectal, and lung cancer.
- Cancer incidence is generally higher in men than in women.
Defects in Cell Proliferation and Differentiation
- Most tissues contain undifferentiated stem cells that differentiate into mature, functioning cells.
- Normal cells maintain a dynamic equilibrium, where cell proliferation balances cell degeneration or death.
- Cell proliferation is activated in response to cell degeneration, death, or physiological needs (e.g., infection).
- Normal cells exhibit contact inhibition, respecting the boundaries of neighboring cells, while cancer cells lose contact inhibition.
- Cancer cells proliferate at the same rate as normal cells but respond differently to intracellular signals, resulting in indiscriminate and continuous growth.
- The pyramid effect describes the continuous growth of a tumor mass as cells divide repeatedly.
- Doubling time refers to the time required for a tumor mass to double in size.
- Cell differentiation is normally an orderly process from immaturity to maturity, with a stable and orderly phasing out of cell potential.
- Cancer cells often exhibit dedifferentiation, reverting to a previous undifferentiated state.
Genetic Link to Cancer
- Cancer involves malfunctioning genes that control cell differentiation and proliferation.
- Proto-oncogenes are normal cell genes that promote growth, while tumor suppressor genes suppress growth.
- Mutations in proto-oncogenes can activate them to function as oncogenes, leading to tumor formation.
- Oncogenes can transform normal cells into malignant cells, which regain a fetal appearance and function.
- Tumour suppressor genes regulate cell growth and prevent cells from entering the cell cycle.
- Mutations in tumor suppressor genes can inactivate them, leading to a loss of their tumor-suppressing action.
Stages of Cancer Development
- Cancer development is a multistage process, typically occurring over time and involving initiation, promotion, and progression.
- Initiation involves a mutation in the cell's genetic structure, a change in the usual DNA sequence.
- Gene mutations can be inherited from a parent or acquired during a person's lifetime.
- Carcinogens (cancer-causing agents) can alter DNA and contribute to cancer development.
- Chemical carcinogens, radiation, and viral carcinogens are known to cause cancer.
- Promotion is characterized by reversible proliferation of altered cells, increasing the likelihood of additional mutations.
- Promoting agents include dietary fat, obesity, cigarette smoking, and alcohol consumption.
- Progression is marked by increased tumor growth rate, invasiveness, and metastasis, the spread of cancer to distant sites.
- Metastasis involves the detachment of tumor cells from the primary tumor, invasion of surrounding tissue, and penetration of lymph or blood vessels.
- Tumor cells need to develop a blood supply, facilitated by tumor angiogenesis factors, for survival and growth.
Role of the Immune System in Cancer
- The immune system distinguishes normal (self) from abnormal (non-self) cells.
- Cancer cells, while arising from normal cells, may display altered cell-surface antigens, called tumor-associated antigens (TAAs).
- Immunological surveillance involves lymphocytes continuously checking cell-surface antigens and destroying cells with abnormal antigens.
- Cytotoxic T-cells, natural killer cells, macrophages, and B-lymphocytes play a role in the immune response to malignant cells.
- Cytotoxic T-cells are capable of killing tumor cells and producing cytokines that stimulate other immune cells.
Natural Killer (NK) Cells
- NK cells can directly kill tumor cells without prior sensitization
- NK cells are stimulated by γ-interferon and IL-2, which are released from T-cells.
- This stimulation results in increased cytotoxic activity of NK cells.
Monocytes and Macrophages
- Macrophages are activated by γ-interferon, which is produced by T-cells, to become lytic for tumor cells.
- Macrophages secrete cytokines including interleukin-1 (IL-1), tumor necrosis factor (TNF), and colony-stimulating factors (CSFs).
- IL-1, along with processed antigen presentation, stimulates T-lymphocyte activation and production.
- α-interferon enhances the killing ability of NK cells
- TNF causes hemorrhagic necrosis of tumors, and has cytocidal or cytostatic effects against them.
- CSFs regulate blood cell production in the bone marrow and stimulate WBC function.
B-lymphocytes
- B-lymphocytes produce specific antibodies that bind to tumor cells.
- These antibodies are often detectable in patient serum and saliva.
Immunological Escape
- Cancer cells evade the immune system through various mechanisms including:
- Suppression of factors that stimulate T-cells to react to cancer cells.
- Weak surface antigens allowing cancer cells to avoid immune surveillance.
- Development of tolerance of the immune system to some tumor antigens.
- Suppression of the immune response by products secreted by cancer cells.
- Induction of suppressor T-cells by the tumor.
- Blocking antibodies that bind TAAs, preventing their recognition by T-cells.
Oncofetal Antigens
- Oncofetal antigens are found on both the surfaces and inside of cancer cells and fetal cells.
- These antigens are a manifestation of the shift of cancerous cells to a more immature metabolic pathway, commonly associated with embryonic or fetal development.
- Examples of oncofetal antigens include:
- Carcinoembryonic antigen (CEA)
- α-fetoprotein (AFP)
- CA-125
- CA-19-9
- Prostate-specific antigen (PSA)
- CA-15-3 and CA-27-29
Tumor Markers
- Oncofetal antigens can be used as tumor markers to monitor therapy effectiveness and indicate tumor recurrence.
- CEA is found on cancer cells derived from the GI tract and normal cells from fetal gut, liver, and pancreas.
- Elevated CEA levels are also observed in non-malignant conditions such as cirrhosis of the liver, ulcerative colitis, and heavy smoking.
- AFP is produced by malignant liver cells and fetal liver cells.
- Elevated AFP levels are also found in testicular carcinoma, viral hepatitis, and non-malignant liver disorders.
- AFP has diagnostic value in primary liver cancer (hepatocellular cancer).
Molecular Markers
- Molecular markers specific to tumors include:
- kRAS (oncogene expression in colon cancer)
- Epidermal growth factor receptor (EGFR) often overexpressed in lung cancer
- Human epidermal growth factor receptor 2 (HER2) expression in breast cancer.
Natural Killer (NK) Cells
- NK cells are able to directly destroy tumor cells without prior sensitization.
- NK cell activity is increased by γ-interferon and IL-2, released from T-cells.
Monocytes and Macrophages
- Macrophages are activated by γ-interferon to become lytic for tumor cells.
- Macrophages release cytokines including IL-1, TNF, and CSFs.
- IL-1 stimulates T-lymphocyte activation and production.
- TNF causes hemorrhagic necrosis of tumors and has cytotoxic or cytostatic effects on tumor cells.
- CSFs regulate blood cell production and stimulate WBC function in the bone marrow.
B-Lymphocytes
- B-lymphocytes produce specific antibodies that bind to tumor cells.
Tumor Immunological Escape Mechanisms
- Cancer cells evade the immune system through various mechanisms, collectively called immunological escape.
- These mechanisms include:
- Suppression of factors that stimulate T-cell recognition of cancer cells.
- Weak surface antigens allow cancer cells to avoid immune surveillance.
- Immune system tolerance to tumor antigens.
- Suppression of the immune response by cancer cell secretions.
- Induction of suppressor T-cells by the tumor.
- Blocking antibodies that bind TAAs, preventing T-cell recognition.
Oncofetal Antigens and Tumor Markers
- Oncofetal antigens are found on the surfaces and inside of both cancer cells and fetal cells.
- These antigens reflect a shift in cancerous cells towards a more immature metabolic pathway, similar to embryonal periods.
- Examples include carcinoembryonic antigen (CEA) and α-fetoprotein (AFP).
- CEA is found on cancer cells from the GI tract and normal cells from the fetal gut, liver, and pancreas.
- AFP is produced by malignant liver cells and fetal liver cells.
- Oncofetal antigens can be used as tumor markers to monitor therapy and indicate tumor recurrence, but they are not 100% specific.
Benign vs Malignant Neoplasms
- Benign neoplasms are well-differentiated, while malignant neoplasms range from well-differentiated to undifferentiated.
- The key difference between benign and malignant neoplasms is the ability of malignant tumor cells to invade and metastasize.
Cancer Classification Systems
- Cancer classification systems help stratify risk, establish standardized communication among healthcare providers, assist in treatment planning, predict prognosis, and compare groups for statistical purposes.
- Classification systems include anatomical site, histology (grading), and extent of disease (staging).
Anatomical Site Classification
- Tumors are identified by tissue of origin, anatomical site, and behavior (benign or malignant).
- Carcinomas originate from the embryonal ectoderm and endoderm.
- Sarcomas originate from the embryonal mesoderm.
- Lymphomas and leukemias originate from the hematopoietic system.
Histological Classification (Grading)
- Histological grading evaluates cell appearance and degree of differentiation.
- Grade I: cells differ slightly from normal cells, well-differentiated (low grade).
- Grade II: cells are more abnormal, moderately differentiated (intermediate grade).
- Grade III: cells are very abnormal, poorly differentiated (high grade).
- Grade IV: cells are immature and undifferentiated, difficult to determine cell of origin (high grade).
- Grade X: grade cannot be assessed.
Extent of Disease Classification (Staging)
- Staging describes the anatomical extent of the disease, not just cell appearance.
Clinical Staging
- Stage 0: cancer in situ.
- Stage I: tumor limited to tissue of origin, localized growth.
- Stage II: limited local spread.
- Stage III: extensive local and regional spread.
- Stage IV: metastasis.
TNM Classification System
- TNM staging determines the anatomical extent of disease based on:
- T: tumor size and invasiveness.
- N: presence or absence of regional lymph node spread.
- M: metastasis to distant organ sites.
Prevention and Early Detection
- Cancer incidence can be reduced through prevention and health promotion.
- Eliminate risk factors to reduce cancer incidence, such as smoking.
- Health promotion strategies include:
- Limiting alcohol use.
- Engage in regular physical activity.
- Maintain a healthy weight.
- Regular colorectal screenings.
- Avoid smoking and tobacco use.
- Regular mammograms and cervical smear tests.
- Sunscreen use with SPF 15 or higher.
- Healthy dietary habits, including reduced fat and increased fruits and vegetables.
Diagnostic Workup
- Diagnostic workup includes:
- Health history.
- Risk factor identification.
- Physical examination.
- Specific diagnostic studies (e.g. cytology studies, tissue biopsy, chest X-ray, blood tests, liver function studies, endoscopic examinations, radiographic studies, radioisotope scans, PET scan, tumor markers, genetic markers, molecular receptor status)
Biopsy Techniques
- A biopsy is the removal of tissue for analysis
- Percutaneous biopsies are performed through the skin
- Endoscopic biopsies can be used for lung and intraluminal lesions
- Surgical procedures are needed for tumors not easily reached
- Radiographic techniques (CT scans, MRI, ultrasound-guided biopsy, stereotactic biopsy, fluoroscopic-assisted biopsy) are used to improve tissue localization
- Fine-needle aspiration (FNA) provides cells for cytological examination
- Large-core biopsy cutting needles deliver a piece of tissue for histological examination
- Excisional biopsy is the surgical removal of the entire lesion and is therapeutic and diagnostic
- Incisional biopsy involves partial excision of the lesion
Pathological Evaluation
- Pathological evaluation is necessary to diagnose a malignancy
- The pathologist determines the nature of the tumor (benign or malignant), tissue of origin, and degree of cell differentiation
- The evaluation also provides information on the extent of malignant involvement, invasiveness, adequacy of surgical excision, and nuclear grade
- Special staining techniques can reveal responsiveness to treatment or disease behavior (receptor status, tumor markers)
Treatment Goals
- Cure, control, and palliation are the main goals of cancer treatment
- Factors determining therapy include tumor histology, staging outcomes, patient's physiological and psychological status, and personal desires
- Treatment modalities include surgery, radiation therapy, chemotherapy, biological and targeted therapy
- Therapies can be used alone or in combination during initial treatment, maintenance therapy, or retreatment
Multimodality Therapy
- Multimodality therapy involves two or more treatment modalities
- It is more effective but increases toxicity
- Evidence-based cancer treatment guidelines are available to guide treatment recommendations
Cure
- Treatment is expected to eradicate the disease
- Curative therapy may involve local therapies (surgery or radiation) alone or in combination with adjunctive systemic therapy (chemotherapy)
- There is no guaranteed cure for most malignancies
- The risk of recurrence is highest after treatment completion and gradually decreases over time
- Cancers with a higher mitotic rate are less likely to recur than cancers with slower mitotic rates
Control
- The goal is to manage cancer that cannot be completely eradicated
- Patients may undergo initial treatment followed by maintenance therapy
- Close monitoring for disease recurrence or progression is crucial
Palliation
- The primary goal is symptom relief and maintaining quality of life
- Palliative care and treatment can occur concurrently
Personalized Cancer Medicine
- Utilizes patient's genetic information to guide prevention, diagnosis, and treatment
- Genetic differences in people and their tumors explain varied responses to treatment
- Next-generation sequencing determines the cause of cancer (hereditary or sporadic)
- Targeted therapy targets specific genes or proteins contributing to cancer growth and survival
Surgical Therapy
- Goal: Remove cancerous tissue and surrounding healthy tissue to prevent cancer development, cure or control existing cancer, or provide supportive care
- Examples of surgical procedures: Mastectomy, orchidectomy, thyroidectomy, nephrectomy, hysterectomy, and oophorectomy.
- Types of surgical procedures: Prophylactic, curative, control, debulking, cytoreductive, neo-adjuvant, supportive, palliative
- Palliative procedures: Examples include debulking of tumor to relieve pain or pressure, colostomy for bowel obstruction relief, and laminectomy for spinal cord compression relief.
Chemotherapy
- Goal: Eliminate or reduce the number of malignant cells in the primary tumor and metastatic sites.
- Mechanism of action: Chemotherapy medications target cells during different phases of the cell cycle, including the resting phase (G0).
- Classifications of chemotherapy medications: Alkylating agents, Nitrosoureas, Platinum drugs, Antimetabolites, Antitumour antibiotics, Mitotic inhibitors, Topoisomerase inhibitors, Corticosteroids, Miscellaneous
Chemotherapy Administration
- Common routes of administration: Intravenous (IV), oral, intramuscular, intracavitary, intrathecal, intra-arterial, perfusion, continuous infusion, subcutaneous, topical
- Concerns with IV administration: Venous access difficulties, device/catheter-related infection, extravasation (infiltration of medications into surrounding tissues)
Regional Chemotherapy Administration
- Goal: Deliver higher concentrations of chemotherapy drugs directly to the tumor site, reducing systemic toxicity.
- Methods of regional delivery: Intra-arterial, intraperitoneal, intrathecal or intraventricular, intravesical bladder chemotherapy.
Effects of Chemotherapy
- Side effects: Result from destruction of normal cells, especially those that proliferate rapidly (bone marrow, GI lining, integumentary system).
- Types of side effects: Acute, delayed, chronic
- Examples of side effects: Myelosuppression, leucopenia, infection, anorexia, mucositis, nausea and vomiting, diarrhea, alopecia, reproductive dysfunction, heart, liver, kidney, lung damage
Radiation Therapy
- Goal: Uses high-energy beams or waves to damage DNA and cause cell death.
- Mechanism of action: The energy from ionizing radiation breaks chemical bonds in DNA.
- Types of radiation therapy: Intensity-modulated radiation therapy (IMRT), image-guided radiation therapy (IGRT)
- Radiation dose: Measured in gray (Gy) or centigray (cGy).
- Fractionation: Total radiation dose is divided into daily fractions, typically 180-200 cGy/day, delivered Monday-Friday for 2-8 weeks.
Radiosensitivity
- Radiosensitivity: The responsiveness of cells and tissues to radiation.
- Factors affecting radiosensitivity: Type of cancer, size and location of tumor, overall health of patient.
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Description
This quiz provides an overview of colorectal cancer, including its origins in the colon and rectum, the structure of the large intestine, and the development of cancerous cells. Additionally, it discusses risk factors and genetic mutations involved in colorectal cancer progression.