1. Cancer Medicine (Oncology)
Chapter 19
Pages 799 – 848

2. Introduction Page 800 Cancer = abnormal and excessive cell growth.
More than ½ of all patients who develop cancer are cured.
Most common causes of cancer death:
Women: Lung, followed by breast and colorectal cancers
Men: lung, colorectal, and prostate cancers
Cancer = abnormal and excessive cell growth. May arise in any tissue and at any time of life, although it occurs most frequently in older people.
More than ½ of all patients who develop cancer are cured. However, About 550,000 people die of cancer each year.
Most common causes of cancer death:
women: Lung, followed by breast and colorectal cancers
men: lung, colorectal, and prostate cancers
In addition to local growth, cancerous cells can spread throughout the body by way of the bloodstream or lymphatic vessels.
In some patients, the spread of caners from the site of origin to distant organs occurs early in the course of tumor growth & ultimately results in death.

3. Characteristics of Tumors
Pages 800 – 801
Characteristics of Tumors
Neoplasms (tumors) = new growths that arise from normal tissue. hyperchromatic =  A condition in which cells or parts of cells, especially cell nuclei, stain more intensely than normal
BENIGN = slow growing
Are often encapsulated (contained within a fibrous capsule or cover), so that the tumor cells do not invade the surrounding tissue.
Are composed of organized & differentiated (specialized) cells that closely resemble the normal, mature tissue from which they are derived.
Do not metastasize to form secondary tumor masses in distant places in the body.
MALIGNANT = grow fast
Compress, invade, and ultimately destroy the surrounding tissue.
Are anaplasia (composed of cells that resemble primitive cells & lack the capacity to perform mature cell functions). Undifferentiated = reverting to a less specialized state
Malignant tumors metastasize (spread).

4. Characteristics of Tumors (cont’d)
Page 801
Characteristics of Tumors (cont’d)
A liver studded with metastatic cancer

5. What Causes Cancer? Page 802 Only partly understood
Malignant transformation = damage to DNA
Must understand DNA and its functions in a normal cell
Carcinogenesis: transformation of a normal cell to a cancerous one. The causes of transformation from a normal cell to a cancerous one are only partly understood.
What is clear is that malignant transformation results from damage to the DNA (deoxyribonucleic acid) or genetic material (is a string of coded nucleotide) of the cell.
nucleotides = containing a sugar, phosphate, & a base, such as adenine, guanine, thymine, or cytosine
In order to understand what causes cancer, it is necessary to learn more about DNA and its functions in a normal cell.

6. DNA Pages 802 – 803 DNA has two main functions in a normal cell.
1) To control cell division
During cell division DNA copies itself so that exactly the same DNA is passed on to two new daughter cells. Strands of DNA in the cell nucleus form chromosomes, which become readily visible under a microscope when a cell is preparing to divide into two (daughter) cells.
2) To control the protein synthesis = specific proteins (such as hormones & enzymes)
Each gene contains the code for making a single protein. That protein carries out an important specific function in the cell. Gene = DNA piece - There are 20,000 to 25,000 human protein-coding genes. Genes are composed of an arrangement of units called nucleotides. DNA sends a molecular message outside the nucleus to the cytoplasm of the cell, directing the synthesis of specific proteins essential for normal cell function & growth.
Central Dogma: Transcription (DNA → RNA) and Translation (RNA → Protein). RNA = ribonucleic acid

7. Carcinogenesis Pages 803 – 804
DNA mutations lead to higher-than-normal rates of growth or keep them from dying.
Malignant cells are anaplastic.
Carcinogens
Chemicals, drugs, and tobacco smoke
Radiation
Viruses
Oncogenes
Although most DNA mutations lead to higher-than-normal rates of growth, some mutations found in cancer cells actually prevent the cells from dying entirely.
Normal cells undergo apoptosis = programed cell death.
Cancer cells reproduce almost continuously, and abnormal proteins are made.
Malignant cells are ANAPLASTIC = their DNA stops making normal codes that allow cells to carry on the function of differentiating mature cells.
Instead, new signals lead to malignant growth and spread of tumor cells.
Carcinogens = Environmental agents that damage DNA. These changes can cause abnormal genes called mutations. Mutations interfere with the accurate synthesis of new proteins & can be passed on to new cells during cell division.
CHEMICALS = hydrocarbons are in cigarette, cigar, pipe smoke & automobile exhaust.
Hormones such as estrogens can cause cancer by stimulating growth of cells in the lining of the uterus or in milk glands of the breast
RADIATION= consists of waves of energy.
Leukemia used to be an occupational hazard of radiologists, who were routinely exposed to x-rays.
There is a high incidence of leukemia and other cancers among survivors of atomic bomb explosions, as at Hiroshima & Nagasaki.
Ultraviolet radiation in sunlight can cause skin cancer, especially in persons with fair skin.
VIRUSES = The human T cell leukemia virus (HTLV1) causes a form of leukemia in adults, herpes virus type 8 causes Kaposi sarcoma, human papillomavirus (HPV) causes cervical cancer & hepatitis B and C viruses cause liver cancer.
Oncogenes = pieces of normal DNA that when activated by a mutation, can convert a normal cell to a cancerous cell.
Examples of oncogenes are: ras (colon cancer), myc (lymphoma), abl (chronic myeloid leukemia or CML)

8. Pages 804
Translocation
In abl (chronic myeloid leukemia or CML) the oncogene abl is activated when pieces from two different chromosomes switch locations. This mutation is called a translocation.
What happens?
The oncogene abl on chromosome 9 moves to a new location next to a gene called bcr on chromosome 22. When bcr (breakpoint cluster region) & abl are near each other, they cause the production of an abnormal protein that makes the leukocyte divide & cause a malignancy CML. The new chromosome formed from the translocation is called the Philadelphia chromosome (it was discovered in 1970 in Philadelphia).

9. Pages 804 – 805
Heredity
Although most caners result from chance mutations in body cells during a lifetime, cancer also may be caused by transmission from parents to offspring through defects in the DNA of the egg or sperm cells.
retinoblastoma (tumor of the retina of the eye)
adenomatous polyposis coli syndrome (premalignant polyps that grow in the colon & rectum)
Wilms tumor (is a type of cancer that starts in the kidneys. It is the most common type of kidney cancer in children)

10. Classification of Cancerous Tumors
Page 805
Classification of Cancerous Tumors
1 2 of cancer deaths = malignancies in lung, breast, or colon
More than 100 distinct types of cancer
Histogenesis
Half of cancer deaths are caused by malignancies that originate in lung, breast, or colon
However, there are more than distinct types of cancer, each having a unique set of symptoms and requiring a specific type of therapy.
Histogenesis = dividing types of cancer into groups on the basis of its tissue of origin.
Carcinomas, Sarcomas, Mixed- tissue tumors

11. Carcinomas Page 806 This is the largest group
Benign → gastric adenoma = a benign tumor of the glandular epithelial cells lining the stomach
Malignant → gastric adenocarcinoma = a cancerous tumor arising from glandular cells lining the stomach
Carcinomas, the largest group (Approx. 90% of all malignancies), are solid tumors that are derived from epithelial tissue that lines external and internal body surfaces, including skin, glands, and digestive, urinary, and reproductive organs.
Benign tumors of epithelial origin are usually designated by the term adenoma, which indicates that the tumor is of epithelial or glandular origin.
Benign = a gastric adenoma is a benign tumor of the glandular epithelial cells lining the stomach.
Malignant tumors of epithelial original are named by using the term carcinoma and adding the type of tissue in which the tumor occurs.
Malignant = Thus, a gastric adenocarcinoma is a cancerous tumor arising from glandular cells lining the stomach.

12. Page 806
Carcinomas and the epithelial tissues from which they derive

13. Page 807
Sarcomas
From connective tissues in the body
Benign → osteoma = a benign tumor of bone
Malignant → osteosarcoma = a malignant tumor of the bone
Comprises approximately 5% of all malignant tumors
They are derived from connective tissues in the body, such as bone, fat, muscle, cartilage, & bone marrow & from cells of the lymphatic system. Often, the term mesenchymal tissue is used to describe embryonic connective tissue from which sarcomas are derived. The mesodermal (middle) layer of the embryo gives rise to the connective tissues of the body as well as to blood & lymphatic vessels
Benign tumors of connective tissue origin are named by adding the suffix –oma to the type of tissue in which the tumor occurs.
Benign = For example, a benign tumor of bone is called an osteoma.
Malignant tumors of connective tissue origin are frequently named using the term sarcoma.
Malignant = For example, an osteosarcoma is a malignant tumor of the bone.

14. Page 807

15. Mixed–Tissue Tumors Page 808
Capable of differentiating into both epithelial and connective tissue.
Uncommon tumors
Examples are found in the kidney, ovaries, and testes.
These tumors are capable of differentiating into both epithelial and connective tissue.
These uncommon tumors are thus composed of several different types of cells
Examples of mixed-tissue tumors are found in the kidney, ovaries, and testes.

16. Pathologic Descriptions: Gross Descriptions
Pages 808 – 809
Pathologic Descriptions: Gross Descriptions
Cystic
Fungating
Inflammatory
Medullary
Cystic = Forming large open spaces filled with fluid (Picture A – note that the tumor has formed fluid-filled cysts and blood-filled sacs.)
Fungating = Mushrooming pattern of growth in which tumor cells pile one on top of another & project from a tissue surface
Inflammatory = Having the features of inflammation - that is, redness, swelling, & heat
Medullary = Large, soft, fleshy tumors (picture B – medullary carcinoma of the thyroid.. Tumor shows a solid pattern of growth.)

17. Pathologic Descriptions: Gross Descriptions (Cont’d)
Pages 808 – 809
Pathologic Descriptions: Gross Descriptions (Cont’d)
Necrotic
Polypoid
Ulcerating
Verrucous
Necrotic = Containing dead tissue (picture A – adenomatous polyposis of the colon. These innumerable polypoid adenmomas have a strong tendency for progression to colon adenocarcinoma.)
Polypoid = Growths that form projections extending outward from a base
Ulcerating = Characterized by an open, exposed surface resulting from the death of overlaying tissue (picture B – Gastric (stomach) carcinoma with a large irregular ulcer).
Verrucous = Resembling a wart-like growth

18. Pathologic Descriptions: Microscopic Descriptions
Pages 809 – 810
Pathologic Descriptions: Microscopic Descriptions
Alveolar
Carcinoma in situ
Diffuse
Dysplastic
Epidermoid
Follicular
Alveolar = Tumor cells form patterns resembling small sacs
carcinoma in situ = Referring to localized tumor cells that have not invaded adjacent structures
Diffuse = Spreading evenly throughout the affected tissue
Dysplastic = Containing abnormal-appearing cells that are not clearly cancerous
Epidermoid = Resembling squamous epithelial cells
Follicular = Forming small glandular sacs (Picture – Follicular non-Hodgkin lymphoma involving a lymph node)

19. Pathologic Descriptions: Microscopic Descriptions (Cont’d)
Pages 809 – 810
Pathologic Descriptions: Microscopic Descriptions (Cont’d)
Papillary
Pleomorphic
Scirrhous
Undifferentiated
Papillary = Forming small, finger-like or nipple-like projections (picture – papillary carcinoma of the thyroid)
Pleomorphic = Composed of a variety of types of cells
Scirrhous = Densely packed tumors, due to dense bands of fibrous tissue
Undifferentiated = Lacking microscopic structures typical of normal mature cells

20. Grading & Staging Systems
Page 811
Grading & Staging Systems
Doctors classify tumors on the basis of
Grade: degree of maturity or differentiation under the microscope
Stage: extent of spread in the body
These two properties influence the diagnosis, treatment, and prognosis for cancer patient.
Doctors classify tumors on the basis of
Grading: degree of maturity or differentiation under the microscope
Patients with grade I tumors have a high survival rate,
patient with grade II, III, & IV tumors have an increasingly poorer survival rate.
Grading also is used in evaluating cells obtained from body fluids in preventive screening tests, such as Pap smears of the uterine cervix.
Staging : extent of spread in the body
The staging of cancerous tumors is based on the extent of spread of the tumor. It relies on careful definition of the size & possible metastatic spread of the tumor, using computed tomography (CT), combination position emission tomography (PET-CT), & magnetic resonance imaging (MRI) scans & radionuclide (radioactive) bone scans. An example of staging system is the tumor-node-metastasis (TNM) International Staging System.
Notations in a staging system are:
T = tumor (size & degree of local extension)
N = nodes (number of regional lymph nodes invaded by tumor cells)
M = metastases (spread of tumor cells to distant sites)
Stage groupings I-IV indicate tumor progression. Thus a stage II group may be designated as T2, N1, M0. Stage IV group indicates any T, any N, & distant metastases.
These two properties influence the diagnosis, treatment, and prognosis for cancer patient.
EXAMPLE of International TNM Staging System for Lung Cancer

21. Cancer Treatment Page 812 Major approaches to cancer treatment are:
Surgery
Radiation therapy
Chemotherapy
Molecularly targeted therapy
Immunotherapy
Major approaches to cancer treatment are:
Surgery
Radiation therapy
Chemotherapy
Molecularly targeted therapy
Immunotherapy
Each modality (method) may be used alone, but often they are used together in combined-modality regimens to improve the overall diagnosis & treatment result. Let’s look closer at each.

22. Cancer Treatment: Surgery
Page 812
Cancer Treatment: Surgery
Many patients with cancer may be cured by surgical excision.
If it metastases,
Dubulking procedure
Then adjuvant (assisting) radiation therapy and/or chemotherapy
Many patients with cancer may be cured by surgical excision.
If it metastases,
Debulking procedure: Surgical removal of the primary tumor prevents local spread or complications, even in the presence of distant disease.
Then the patient receives Adjuvant (assisting) radiation therapy and/or Chemotherapy to prevent recurrence at local and distant sites.
Some common cancers in which surgery may be curative are those of the stomach, breast, colon, lung, & uterus.

23. Cancer Treatment: Surgery
Page 812
Cancer Treatment: Surgery
cauterization
exenteration
core needle biopsy
fine needle aspiration
cryosurgery
fulguration
en bloc resection
incisional biopsy
excisional biopsy
Cauterization – Destruction of tissue by burning
core needle biopsy – Placement of a large-bore needle that extracts a thin core of tissue
cryosurgery – Use of subfreezing temperature to destroy tissue
en bloc resection – Tumor is removed along with a large area of surrounding tissue containing lymph nodes.
excisional biopsy – Removal of tumor and a margin of normal tissue
exenteration – Wide resection involving removal of the tumor, its organ of origin, and all surrounding tissue in the body space.
fine needle aspiration – Placement of a very thin needle inside the tumor mass & extracting cells for microscopic evaluation
fulguration – Destruction of tissue by electric sparks generated by a high-frequency current
incisional biopsy – Piece of tumor is removed for examination to establish a diagnosis

24. Cancer Treatment: Radiation Therapy
Page 812
Cancer Treatment: Radiation Therapy
Goal → maximal dose of radiation to the tumor and minimal dose to the surrounding tissue.
Newer techniques
The goal of radiation therapy (Radiation Oncology) is to deliver a maximal dose of ionizing radiation to the tumor and a minimal dose to the surrounding tissue.
High-dose irradiation (exposure of tissue to radiation) destroys tumor cells and produces damage to DNA.
Newer techniques of irradiation use high-energy beams of protons (subatomic particles) to improve the uniformity (conformity) of dose and to limit damage to normal tissues.

25. Cancer Treatment: Radiation Therapy
Page 813
Cancer Treatment: Radiation Therapy
Brachytherapy
Electron beams
External beam radiation (teletherapy)
Fields
Brachytherapy - Implantation of small, sealed containers or seeds of radioactive material directly into the tumor; or in a cavity of the tumor.
electron beams - Low-energy beams for treatment of skin or surface tumors
external beam irradiation - Radiation therapy applied to a tumor from a distant source
Fields - Dimensions of the size of radiation area used to treat a tumor from a specific angle
(Picture – Radiation fields – three-color radiation dose distribution image showing radiation fields used to treat a brain tumor)

26. Cancer Treatment: Radiation Therapy
Page 813
Cancer Treatment: Radiation Therapy
Fractionation
Gray (Gy)
Linear accelerator
Photon therapy
Proton therapy
Fractionation - A method of dividing radiation into small, repeated doses rather than fewer large doses.
gray (Gy) - Unit of absorbed radiation dose
linear accelerator - Large electronic device that produces high-energy x-ray beams for the treatment of deep-seated tumors.
(Picture – Linear accelerator. Radiation therapy delivered to a patient position under a linear accelerator. IMRT is an advanced mode of high-precision radiotherapy that uses computer controlled liner accelerators to deliver precise radiation doses to a malignant tumor. This is a type of conformal radiation therapy that uses computer technology to created a three-dimensional image of a tumor so that rotating beams can shape exactly to the contour of the tumor.)
photon therapy - Radiation therapy using x-rays or gamma rays
proton therapy - Small subatomic positively charged particles produced by a cyclotron deposit all the energy at a focused finite point.
(Picture A – Proton therapy machine. Proton beam radiation therapy is useful in treating a variety of cancers including tumors of the head and neck, brain, eye, and prostate.)

27. Cancer Treatment: Radiation Therapy
Page 813
Cancer Treatment: Radiation Therapy
Radiocurable tumor
Radioresistant tumor
Radiosensitive tumor
Radiosensitizers
Simulation
Stereotactic radiosurgery
radiocurable tumor - Tumor that can be completely eradicated by radiation therapy
radioresistant tumor - Tumor that requires large doses of radiation to produce death of the cells
Radiosensitizer - Drugs that increase the sensitivity of tumors to x-rays
radiosensitive tumor - Tumor in which irradiation can cause that death of cells without serious damage to surrounding tissue
Simulation - An imaging study performed before radiation therapy using CT scan &/or MRI to map the area to receive treatment.
stereotactic radiosurgery - Single large dose of radiation is delivered under precise three-dimensional guidance from multiple angles to destroy vascular abnormalities & small brain tumors.
(Picture B – Proton stereotactic radiosurgery. A model poses to show how a proton beam device is brought near a patient in preparation for stereotactic radiosurgery.)

28. Radiation Therapy Side Effects
Page 815
Radiation Therapy Side Effects
Alopecia
Nausea and vomiting
Fibrosis
Pneumonitis
Infertility
Secondary tumors
Mucositis
Xerostomia
Myelosuppression
Alopecia (baldness)
Fibrosis (increase in connective tissue)
Infertility (inability to contribute to conception of a child)
Mucositis (inflammation and ulceration of mucous membranes)
Myelosuppression (bone marrow depression)
Nausea and vomiting
Pneumonitis (inflammation of the walls of the alveoli in the lungs, usually caused by a virus)
Secondary tumors (new types of tumors)
Xerostomia (dryness of mouth)

29. Cancer Treatment: Chemotherapy
Page 816
Cancer Treatment: Chemotherapy
Treatment of cancer using chemicals
Chemotherapy may be used alone or in combination
Combination chemotherapy
Treatment of cancer using chemicals. It is the standard treatment for many types of cancer, and is curative in a number of them, such as testicular cancer, acute lymphocytic leukemia, Hodgkin lymphoma, and large cell lymphomas.
Drugs cause tumor cells to die by damaging their DNA. Tumor cells with damaged DNA undergo apoptosis (self-destruction). This means that they have less capacity to repair their DNA and, in general are less able to survive DNA damage caused by drugs & radiation.
The ideal is to administer drugs that kill large numbers of tumor cells without harming normal cells. However, rapidly dividing normal cells, such as in the bone marrow & gastrointestinal lining, can suffer considerable damage from chemotherapeutic drug
Chemotherapy may be used alone or in combination with surgery and irradiation to improve cure rates.
Combination chemotherapy is the use of two or more drugs together to kill tumors. *

30. Categories of Chemotherapeutic Agents
Page 817
Categories of Chemotherapeutic Agents
Alkylating agents
Antibiotics
Antimetabolites
Antimitotics
Hormonal agents
Alkylating agents - These drugs cause crosslinks & breaks in DNA that interfere with cell division
Antibiotics - These drugs are produced by bacteria or fungi & inhibit cell division by causing breaks in DNA strands.
Antimetabolites - These drugs blocks synthesis of DNA components & prevent cells from dividing
Antimitotics - These chemicals block the function of a protein that is necessary for mitosis.
Hormonal agents – These drugs block hormone receptors on cells so that growth is inhibited
Figure 19-2 illustrates the mechanisms of action for various types of cancer chemotherapeutic agents. Often, drugs are admistered in combination, according to carefully planned protocols (regimens).

31. This table lists specific chemotherapeutic drugs in each category and the type of cancer they treat.

32. Cancer Treatment: Molecularly Targeted Therapy
Page 819
Cancer Treatment: Molecularly Targeted Therapy
Attack specific mutations that drive cancer growth
Cancer cells dies
Not found in normal tissues
Little or no effect on normal cells
Molecularly targeted cancer therapy uses drugs to attack specific mutations that drive cancer growth.
When these targets are blocked by drugs, the cancer cells dies.
Some of the targets are absolutely unique to tumor cells & not found in normal tissues.
Thus, in contrast with chemotherapy, blocking these targets will have little or no effect on normal cells.
Chemotherapeutic drugs normally are delivered by intravenous infusions, whereas molecularly targeted drugs often are given orally, in pill form.

33. Cancer Treatment: Immunotherapy
Page 819
Cancer Treatment: Immunotherapy
Use of immune cells or antibodies, to kill tumors. Examples:
Modified T cells
Herceptin that blocks a receptor then attacks a growth factor
Nivolumb blocks a protein on tumor cells
Immunotherapy is the use of immune cells or antibodies, to kill tumors. An antibody that will attack a target on the tumor cell surface.
Examples:
T cells that have been modified in a laboratory to recognize and destroy a patient’s own tumor.
This therapy is effective against acute lymphoid leukemia (ALL) and chronic lymphoid leukemia (CLL).
Herceptin blocks a receptor and destroys a growth factor on the surface of breast cancer cells.
Nivolumb works by blocking a protein on tumor cells.
It is effective against melanoma, lung cancer, bladder cancer, kidney cancer, & Hodgkin lymphoma.

34. Laboratory Tests Page 826 cytogentic analysis immunohistochemistry
protein marker tests
cytogentic analysis – Chromosomes of normal or tumor cells are examined for breaks
immunohistochemistry – Localization of antigens or proteins in tissues using labeled (colored or fluorescent) antibodies.
protein marker tests – Measures the level of proteins in the blood or on the surface of tumor cells

35. Clinical Procedures Pages 826 – 828 Bone marrow biopsy
Bone marrow or stem cell transplant
Core needle biopsy
Exfoliative cytology
Fiberoptic colonoscopy
Laparoscopy
bone marrow biopsy - Aspiration of bone marrow tissue & examination under a microscope for evidence of malignant cells
bone marrow or stem cell transplantation - Bone marrow or stem cells are infused intravenously into a patient
core needle biopsy - Insertion of a large-bore needle into tissue to remove a core of cells for microscopic examination
exfoliative cytology - Cells are scraped from the region of suspected disease & examined under a microscope
(Picture A – Normal exfoliative cytologic smear (Pap smear) from the cervicovaginal region. It shows flattened squamous cells and some neutrophils as well.)
(Picture B – Abnormal cervicovaginal smear shows numerous malignant cells that have pleomorphic (irregularly shaped) and hyperchromatic (stained) nuclei.
fiberoptic colonoscopy - Visual examination of the colon using a fiber-optic instrument
Laparoscopy - Visual examination of the abdominal cavity using small incisions & a laparoscope

36. Clinical Procedures (Cont’d)
Pages 826 – 828
Clinical Procedures (Cont’d)
Mammography
PET-CT Scan
Radionuclide scans
mammography - X-ray examination of the breast to detect breast cancer
PET-CT Scan - Diagnostic procedure combining CT & PET
(Picture – PET-CT Scan shown captures three areas of increased radioactiviy, seen in the lymph nodes of the left axilla (armpit). By overlaying PET and CT images, physicians can identify spread of malignancy or metastasis. Brain and heart activity are normal.
radionuclide scans - Radioactive substances are injected intravenously, & scans of organs are obtained.