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Hyperplasia

Hypertrophy

Atrophy

Metaplasia

Dysplasia

Hyperplasia - Inc cell #

Hypertrophy - Inc cell size
Atrophy - ↓ size and/or # of cells

Hyperplasia, hypertrophy & atrophy may represent physiologic responses to normal development (fetal growth, skin ...) or a pathologic change in response to a disease process

Metaplasia – a change from one type of differentiated tissue to another

Dysplasia – disordered growth; often a precursor of malignancy

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Neoplastic proliferation is...

a proliferation of cells which persists after the stimulus which initiated it has been withdrawn. It is autonomous. It is:

1) Progressive

2) Purposeless

3) Regardless of surrounding tissue

4) Not related to needs of body

5) Parasitic

Neoplastic cells are transformed and the normal mechanisms that control cellular proliferation & maturation FAIL

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Benign Tumors vs Malignant Tumors

Clinical features

Gross appearance

Clinical features:

Slow                              Growth                      Rapid
Rare                            Ulceration                    Frequent
Rare                          Hemorrhage                   Frequent
No                       Evidence of metastasis          Frequent

Gross appearance:

Tumour edge

B: Smooth, due to expansile growth; May be encapsulated
M: Irregular, due to infiltrative growth

Cut surface:

B: Bland, homogeneous
M: Variegated, due to haemorrhage & necrosis

Evidence of secondary:

B: No Spread
M: Draining lymph nodes or adjacent structures may obviously be infiltrated

Microscopic features:

Resemblance to tissue of origin:

B: Good
M: Often poor

Cell size and shape:

B: Fairly uniform
M: Highly variable (pleomorphic)

Mitotic figures:

B: Very few, all normal
M: Often numerous, frequently abnormal mitoses

Invasion of blood vessels/ Lymphatics/perineural space:

B: No
M: Often present

Dysplasia in adjacent tissues:

B: No
M: Sometimes (e.g. cervix, skin, stomach)

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Malignant neoplasm

Classification of tumours - Epithelium

Neoplastic cells in malignant neoplasms have potentially lethal characteristics enabling them to invade and metastasize (spread) to other tissues

Benign epithelial tumours are papillomas or adenomas and a malignant tumor of Epithelium is called a Carcinoma:

Squamous, e.g. skin
B: Squamous papilloma (papilloma = benign)
M: Squamous carcinoma

Glandular, e.g. gastrointestinal tract
B: Adenoma
M: Adenocarcinoma

Transitional, e.g. urothelium
B: Transitional cell papilloma
M: Transitional cell carcinoma

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Classification of tumours - Connective tissue

Malignant Tumor of mesenchyme = Sarcoma

Fat
B: Lipoma
M: Liposarcoma

Muscle: i. Smooth Muscle, e.g. wall of GI tract
B: Leiomyoma
M: Leiomyosarcoma

Muscle: ii. Striated Muscle, i.e. voluntary muscle
B: Rhabdomyoma
M: Rhabdomyosarcoma

Fibrous tissue, e.g. tendon
B: Fibroma
M: Fibrosarcoma

Cartilage
B: Chondroma
M: Chondrosarcoma

Bone
B: Osteoma
M: Osteosarcoma

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 Tumor of Lymphoid cells

Tumor of Plasma cells

Tumor of Central nervous system (e.g. glial cells)

Tumor of Melanocyte

Note:

Lymphoid cells  = Lymphocytic leukemias or Lymphomas

Plasma cells = Myeloma

CNS = Glioma (same name benign and malignant)

Melanocyte = Melanoma

Note: These are special categories of tumours. Tumours that do not fit epithelial or mesenchymal (support cell) categories -> Inconsistent naming! But all are malignant:

Lymphoma
Leukemia
Melanoma (malignant melanoma)
Embryonal tumours (“-blastoma”)

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Tumour shapes (pic of slide)

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Grading of tumours

and Staging

Ascites definition

Grading reflects cellular features:
Well differentiated (resemble cell of origin)
Poorly differentiated (disorganised growth pattern)-> worse

Staging reflects extent of spread:

TNM system:

T - Tumor (size)
N-  Nodes (is there cancer in the lymph nodes?)
M - Metastasis

There are others also (Dukes’ staging of colorectal carcinoma etc...)

Ascites: accumulation of free fluid in abdominal cavity (with cirrhosis of liver, intraabdominal cancer, congestive heart failure…)

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Features of neoplastic cells (atypical cytology)

What is Oncology?

What makes a tumor “malignant”?

1. Variable size & shape of nuclei (pleomorphic)
2. Densely staining nuclei (hyperchromatic)
3. Disproportionately large nuclei relative to cytopasm (Inc nuclear:cytoplasmic ratio -> n:c ratio)
4. Mitoses

The study of the development, diagnosis, treatment, and prevention of tumors

• Uncontrolled growth
• proliferation of abnormal clones
• Unregulated growth
• “lack of death” (inhibition of apoptosis)
• Genetic  disabilities
• Invasion
• Metastatic (“spreading”) potential
• Angiogenesis (imptnt)

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How common is Cancer?

• World:
• 1 in 4 deaths in developed countries
• 13% of all deaths (7.6 million deaths/year)
• Canada:
• 177,900 new cases, 75,000 deaths
• 38% of Canadian women and 41% of Canadian men will develop cancer in their lifetime

In men (most common):

1. Prostate
2. Lung

3. Colorectal

In women (most common):

1. Breast

2. Lung

3. Colorectal

Deaths (men and women):

1) Lung
2) Colon
3) Breast
4) Prostate

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What is carcinogenesis?

What are some risk factors for

developing cancer? (4 types)

• The initiation of cancer formation
• Disruption of the normal cell balance between proliferation and apoptosis (programmed cell death)
• Genotoxic (DNA damaging) agents
• Multistep process

Chemical factors:
Cigarette smoke, asbestos, arsenic

Physical factors:
Ionizing and Solar radiation
Heat
Chronic trauma ->repetitive trauma or inflammation

Viral factors:
Ebstein Barr virus, Hepatitis B, Human Papilloma Virus

Family History

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How do we screen for colorectal cancer?

Tumor must be....to be seen

For all individuals over 50 of average risk:

• 3-sample FOBT yearly
• Sigmoidoscopy every 5 years
• 3-sample FOBT yearly + sigmoidoscopy every 5 years
• Colonoscopy every 10 years
• Barium enema every 5 years

Despite its prevelance, only 17% of canadians do this!

mass of 10⁹ cells (about 1 gram) before it becomes clinically evident

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Tumor Growth Rate Factors (3)

Where should we target cell growth? (4)

1. Growth Fraction
Percentage of growing cells within the tumor

Range in cancers: 30-70%

2. Cell cycle time (Doubling time)
Burkitt’s Lymphoma               (1 day)
Testicular Cancer                   (5 days)
Colon Cancer                         (80 days)
NSCLC                                  (90 days)

3. Rate of cell death

1. Macromolecular synthesis and function
2. Cytoplasmic organization and signal transduction
3. Cell membrane and associated cell surface receptor synthesis, expression and function
4. Environment of cancer cell growth

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What % of cancer is preventable?

What is Erlotinib (Tarceva)?

1/3

• A pill
• Targets a specific growth receptor on the the cell
• New data showing increased survival in second and third line settings in non-small cell lung cancer

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Metaplasia

Dysplasia

Metaplasia - change from one type of differentiated tissue to another

• Reversible if the stimulus is removed
• Not pre-malignant
• At Inc risk of developing dysplasia, which is pre-malignant

Dysplasia – disordered growth; often a precursor of malignancy

• Abnormal cytologic features (atypia) & abnormal architecture
• PRE-CANCEROUS
• Differs from cancer in extent of abnormal changes
• early dysplasia may revert to normal if stimulus removed
• severe dysplasia progresses to cancer if untreated
  ie -> carcinoma in situ

Inc Nuclear atypia correlates to inc risk of progression to cancer

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Changes in basement membrane for

dysplasia and carcinoma

Dysplasia or carcinoma in situ: No invasion of tumour cells through epithelial basement membrane (growth on luminal side)

Invasive carcinoma: Basement membrane invaded

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Which of the following is false?
a) The progression to cancer is multistep.
b) Invasion of the basement membrane is a critical step in the progression to invasive carcinoma.
c) Metaplasia is reversible if the stimulant or irritant is removed.
d) Cancer continues to progress after the initiating stimulus is removed.
e) The pathologist cannot detect early changes so why bother with screening programmes.

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Tumour invasion: infiltrating ductal carcinoma in breast...

Cancer cell invasion steps (3)

Leads to Peau d’orange and Nipple retraction

Occurs when the lymphatics are blocked and this maty also trigger formation of fibrous tissue

1. Cancer Cells have the ability to secrete lytic enzymes (eg collagenases) -> basement membrane breached

2. These cells are less adhesive than usual (due to loss of cell adhesion molecs)

3. Cells pass basement memb and spead through body (b. vessels and lymphatics) = metastasis

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Invasion & Metastasis Multistep Events

1) Invade basement membrane under tumour
2) Move through extracellular matrix
3) Penetrate vascular or lymphatic channels
4) Survive in circulating blood or lymph nodes
5) Exit circulation into new tissue site
6) Survive & grow as metastasis

Following invasion, malignant cells spread to distant sites in a few steps:
1) Invade & survive in circulation - evade destruction by immune cells
2) Escape from circulation
3) Local growth - angiogenesis

New vascular supply needed for tumour grow >1mm

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Main routes of metastatic spread (6)

1) hematogenous via veins & arteries - eg osteosarcoma spreads to lungs or GI carcinoma to liver via HPV
2) lymphatic - eg carcinoma of breast

Also:

3) seeding of body cavities (transcoelomic spread - eg gastric carcinoma cells seeding through peritoneal cavity)

4) via cerebrospinal fluid (CSF)
5) Direct - Mediastinal tumor compressing superior vena cava

6) Field Change - eg. Transitional change carcinoma

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Characterizing Lymphatic spread

Characterizing Hematogenous spread

Tumour cells form tumour emboli in lymph stream -> travel to the nearest node (sentinel node)

If we ID sentinal node we can assess wheter the tumor has metastasized

Tumour cells invade venules or by lymphatic embolism through thoracic duct into subclavian vein.

Note: Direct invasion of arteries is rare (thicker walls)

Possible sequelae:
1. Tumour embolism to lungs (systemic circulation)
2. Embolism to liver (portal circulation)
3. Embolism via pulmonary veins to systemic arterial circulation e.g. to brain (or other organs too)

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Tumours metastatic to brain: Common primary sources (4)

Clonal origin & evolution

1. Lung

2. Breast

3. Kidney

4. Melanoma

Most cancers arise from a single transformed cell (monoclonal origin). Tumour cells progressively accumulate new mutations as they proliferate -> generate diverse population of genetically different cells.

This leads to tumor heterogeneity

SF105

Which of the following is true:
e) the degree of anaplasia does not generally correlate with the aggressiveness of a tumor
d) anaplastic features are unrelated to dysplasia
c) dysplastic epithelium is unrelated to carcinoma in situ
b) dysplastic epithelium always leads to carcinoma in situ
a) dysplastic epithelium may lead to carcinoma in situ

Which is true:
a) Diagnosis of malignancy can never be made on the basis of local invasion
b) The presence of metastases identifies a tumor as malignant
c) Malignant tumors resemble their parent tissue morphologically and functionally
d) Malignant cells have no capacity to invade surrounding tissue
e) Metastatic spread is a rare cause of cancer death

a) dysplastic epithelium may lead to carcinoma in situ

b) The presence of metastases identifies a tumor as malignant

SF105

Which is true
a) only rare cancers metastisize by a hematogenous route
b) breast cancer never metastasizeses by the lymphatic network
c) metastasis of breast cancer is often by the lymphatic network
d) the identification of a sentinel lymph nodes is not helpful in assessing the metastasis of breast cancer
e) breast cancer in a lymph node is not proof of metastasis

Which is true
a) metastasis does not involve the spread of tumor to distant sites
b) metastasis never involves invasion of the circulation
c) tumor cells do not commonly invade capillaries and veins
d) malignant tumors arising in organs adjacent to body cavities (ie ovaries) never shed malignant cells into these spaces
e) tumor cells may reach the brain through arterial dissemination

Which is true:
a) invasion of the basement membrane underlying a neoplasm is not a critical step towards metastasis
b) the basement membrane is not involved in carcinoma progression
c) carcinoma in situ is confined to the epithelium in which it arises
d) invasion and metastasis are not multistep events
e) liver and lung are rare sites of metastasis

c) metastasis of breast cancer is often by the lymphatic network

e) tumor cells may reach the brain through arterial dissemination

c) carcinoma in situ is confined to the epithelium in which it arises

SF127

Clinical Staging vs Pathologic Staging

The “TNM” Staging System

Clinical Staging: based on physical exam, radiographs, CT scans, isotopic scans and other imaging procedures

Pathologic Staging: information obtained during a surgical procedure

“T”  tumor  (local extent) - size of the tumor

“N”  Node  (regional extent)

“M”  Metastasis  (distant extent)

SF127

What are Tumor Markers? (Examples)

• Substance found in blood or urine that can be elevated in certain cancers
• Usually a protein
• NOT FOR SCREENING
  

Examples:

Carcinoembryonic antigen (CEA)

Colon cancer

Alpha-fetoprotein (AFP)

Testicular cancer

Liver cancer

Cancer Antigen 125 (CA 125)

Ovarian cancer

Lactate dehydrogenase (LDH)

Testicular cancer

Small Cell Lung Cancer

Prostate Specific Antigen (PSA)

Prostate Cancer

SF119

Neoplasia arises from mutations in

genes that regulate... (3)

Categories of “transforming genes” (3)

1. Cell growth

2. Apoptosis

3. DNA repair

Categories of “transforming genes”:
• Oncogenes
• Tumour suppressor genes
• DNA mismatch repair genes

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 Protooncogenes are...

Tumour suppressor genes are...

 Oncogenes Mechanisms of activation (3)

Protooncogenes are NORMAL genes that stimulate cell division. When they mutate they become oncogenes

Tumour suppressor genes are NORMAL genes that inhibit cell division (Ex Rb, P53)

When stimulators > inhibitors we get growth -> cancer

• By mutation
• By chromosomal translocation
• Chronic myeloid leukemia (CML)
• The Philadelphia chromosome (aquired CML)
• Burkitt Lymphoma
• Acute myeloid leukemia (AML)
• By gene amplification
• E.g. erbB2 (HER2/neu) protooncogene is amplified in up to 1/3 of breast & ovarian cancers

Choose the false statement:
a) Chromosomal translocations have been implicated in the pathogenesis of some leukemias & lymphomas.
b) CML, Burkitt lymphoma, & APL are malignancies initiated by chromosomal translocations.
c) Cell growth is regulated without “checkpoints” in the cell cycle.
d) The normal controls regulating the balance between factors stimulating & inhibiting cell growth are defective in cancer cells, resulting in inc cell proliferation.
e) Tumour suppressor genes are normal genes with products that inhibit cellular proliferation.

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Protooncogenes have roles in...

What are tumour suppressor genes?

biochemical pathways regulating growth & differentiation.

In cancer cells normal protooncogenes are changed permanently to ONCOGENES->uncontrolled proliferation

"Gatekeepers”: normal genes with inhibitory function in control of cell cycle

If this normal function is lost then critical regulation of cell cycle is lost (inhibition at checkpoints is lifted)

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Rb (retinoblastoma) gene inactivation

• 40% of cases are associated with germline mutation; remainder are sporadic
• Present with Leukocoria: abnormal white reflection from retina instead of “red eye” in photos with flash
• Histology: Rosettes (no idea why)
• Inc risk of osteosarcomas
• The “two-hit” origin of retinoblastoma
• Inherited retinoblastoma: Person starts with 1 "hit", need 1 more mutation to get retinoblastoma
• Sporadic retinoblastoma: both alleles need to undergo seperate muatations: less likely

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p53 gene

Choose the false statement
a) Oncogenes are altered versions of normal genes (proto-oncogenes).
b) Mutations activate proto-oncogenes to become oncogenes.
c) Tumour suppressor genes are altered genes with products that inhibit cellular proliferation.
d) Mutations inactivate the normal inhibitory activities of tumour suppressor genes.
e) Rb and p53 are tumour suppressor genes.

“Guardian of the genome”

• codes for a nuclear protein which is expressed in increased amounts following cellular damage
• when you have cell damage p53 stops cell in cycle until repaired or apoptosis
• If p53 deficient, damaged cells will continue in cycle which can lead to cancer

c) Tumour suppressor genes are altered genes with products that inhibit cellular proliferation.

SF119

DNA repair genes

Choose the false statement:
a) Neoplasia arises from mutations in genes that regulate cell growth, apoptosis, or DNA repair.
b) The link between EBV-associated Burkitt lymphoma & malaria is thought to be related to dysregulation of the immune system.
c) Rb and p53 act as inhibitors at checkpoints in the cell cycle.
d) Mutations of Rb & p53 result in loss of inhibition (i.e. disinhibition – the cell passes the checkpoint into the cell cycle).
e) Rb & p53 are oncogenes.

“Caretaker” genes

• Alterations in DNA repair genes BRCA1 & BRCA2 -> inc predisposition to breast & ovarian cancer (BRCA1) or ovarian cancer (BRCA2)
• Hereditary nonpolyposis colon cancer syndrome (HNPCC) results from defects in DNA repair genes (microsatellite instability)

e) Rb & p53 are oncogenes

SF119

Viruses & cancer (3)

Viral Carcinogenesis

Human papilloma virus (HPV) is associated with cervical cancer

Epstein-Barr virus (EBV) is associated with Hodgkins Lymphoma (owl eyes) Burkitt lymphoma (starry night) and -> closely linked with Malaria in Africa

Human herpes virus 8 (HHV8) is associated with Castleman disease/Lymphoma (onion skin)

Pic missing, see if you can find it! Slide 53

SF119

Choose the false statement:
a)EBV is associated with Burkitt lymphoma
b)HPV is associated with cervical cancer
c)There is no known association between EBV & Hodgkin lymphoma
d)Burkitt lymphoma is localised in Africa where malaria is endemic
e)HHV8-associated malignancies include a lymphoma arising in Castleman disease

Chemical carcinogenesis: Stages of initiation & promotion

c)There is no known association between EBV & Hodgkin lymphoma

*missed diagram - look back*

For it to work we need:

Initiator first, then promotor at optimal time intervals. Nothing else will work.

SF119

Physical carcinogenesis

Effects of radiation on cells

• Ultraviolet (UV) radiation -> skin cancers
• Asbestos causes mesothelioma
• malignant mesothelioma of pleural & peritonwal cavities
• latent period (i.e. between exposure & appearance of tumour) ~ 20 years
• asbestos fibres transported to pleura & peritoneum by lymphatic channels

radiation -> dysjunction -> random fusion of broken ends -> mutation

• Range of damage: single gene mutation to major chromosome damage including breaks, deletions, translocations
• Ionising radiation damages the cell’s DNA especially during cell proliferation
• Especially vulnerable = proliferating cells
• e.g. bone marrow, gut mucosa
• There can be a long latency period, or not

SF119

Choose the false statement:
a) Asbestos causes mesothelioma.
b) Regarding chemical carcinogenesis: the initiator must be applied before the promotor, and the promotor must be applied repeatedly & at regular intervals.
c) A radiation-induced tumour would not appear years following irradiation.
d) A white-skinned person in a sunny climate is at higher risk of developing melanoma than one in a cold grey country, or than a dark-skinned person.
e) Some tissues, e.g. bone marrow, gut mucosa, & thyroid (in the young), are particularly sensitive to the effects of radiation.

Tumour syndromes (2 examples)

c) A radiation-induced tumour would not appear years following irradiation.

Neurofibromatosis type 1:

Forms many neurofibromas -> multiple thoracolumbar nerve sheath tumours

Familial adenomatous polyposis (FAP):

Adenomatous polyposis coli (APC) genes: tumour suppressor genes

Affected individuals develop thousands of adenomatous polyps in colon during their teens or 20s -> malignant transformation of polyps -> colon cancer

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The colonic adenoma-carcinoma sequence (5)

Both benign & malignant tumours can cause death

1. Mutation produces a hyperproliferative epithelial focus
2. Further DNA alterations lead to formation of a small adenoma
3. Further mutation produces an intermediate adenoma
4. Further mutation produces a large adenoma
5. Another mutation leads to development of invasive cancer Other mutations may confer ability to metastasize

Coles notes:

Multistep carcinogenesis: accumulated DNA damage impairs cell cycle control -> allows further mutations

• Malignant tumours, once disseminated, often lead to death – main reasons:
• Cachexia, poor nutrition, progressive weakness, secondary infection, e.g. pneumonia
• Damage or obliteration of vital organ or system
• Most benign tumours are not life-threatening but their location may be critical in influencing outcome, e.g. “benign” tumour of brainstem

SF119

Effects of cancer (7 examples)

1. Systemic – fever, weight loss, cachexia
2. Paraneoplastic syndromes
3. Neurologic complications
4. Skeletal muscle syndromes, e.g. dermatomyositis
5. Hematologic complications due to direct infiltration of bone marrow or treatment
6. A hypercoagulable state
       –Venous thrombosis
       –Disseminated intravascular coagulation (DIC)
7. Amyloidosis associated with cancer

SF119

Paraneoplastic syndrome

Choose the false statement:
a) The designation of “benign” does not fit a low-grade brain tumour in a critical site.
b) Paraneoplastic syndromes are related to the production of bioactive substances by the tumour.
c) Cushing’s syndrome is due to cortisol deficiency.
d) Neurofibromas may undergo malignant transformation.
e) “B” symptoms in a patient with Hodgkin lymphoma include fever, drenching sweats, & weight loss.

Caused by bioactive agent produced by tumour or as a consequence of tumour (not due simply to mass effect of tumour)

Ex:

• Lambert-Eaton syndrome (autoimmune response against presynaptic component of neuromuscular junction – causes muscle weakness)
• Cushing’s syndrome (due to cortisol excess)
• Cushing’s disease when due to pituitary adenoma

c) Cushing’s syndrome is due to cortisol deficiency

SF119

Choose the false statement:
a) Lymphedema may be a direct effect of tumour or an effect of treatment.
b) Hypercoagulability is rare in patients with cancer.
c) Deep venous thrombosis (DVT) or pulmonary embolism (PE) may be a sign of underlying malignancy.
d) Angiosarcoma is a malignant vascular neoplasm.
e) Tumour cells can evade immunologic destruction.

Epidemiology:
Hepatocellular carcinoma

Malignant melanoma

Gastric carcinoma

b) Hypercoagulability is rare in patients with cancer

Hepatocellular carcinoma

Sub-Saharan black Africa, Far East

Malignant melanoma

Australia, Scandinavia

North America: Californian whites at highest risk

Gastric carcinoma

Japan, China, Brazil, Colombia, Chile, Iceland, Finland, USSR, Poland, Hungary

SF133

Adjuvant Therapy

Neoadjuvant Therapy

• Any kind of treatment given after “definitive treatment” and all detectable disease has been removed
• Can be chemotherapy or radiotherapy
• Assumed that proportion of patients will have already been cured by their surgery
  
  Tumors that show improved survival benefit from adjuvant chemotherapy:
• Lung, Breast, Colon (imptnt ones) and lots of others

Treatment given before definitive curable resection

Usually aimed to make the surgery “easier” with a higher chance of eliminating macroscopic disease:
Good side:

• Can shrink the tumor and make surgery easier
• Intact blood supply means theoretically higher delivery of chemotherapy
• Good test of tumor sensitivity or resistance to the choosen chemotherapy regimen

Bad side:

• Delaying definitive curative surgical treatment
• Possibly could induce chemotherapeutic resistance and decrease benefit of adjuvant therapy
• No improvement in overall survival

Used in: Breast cancer, Rectal cancer, Bladder Cancer and Gastric and Gastroesophageal cancer

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Palliative Systemic Therapy

Main side FX of Chemo

• Chemotherapy not aimed at complete cure
• Improve symptoms:
• Dysphagia, Dyspnea, Pain
• Paraneoplastic syndromes
• Improve quality of life
• Improve overall survival in:
• Lung, Breast, Colon, Prostate, Gastric and Pancreas

Nausea and Myelosuppression

SF133

4 main chemo drugs

Cisplatin:

inhibits DNA synthesis by creating DNA cross-links (intercalation) which interferes with mitosis

The most nauseating of all chemotherapy

Cyclophosphamide:

alkylating agent that prevents cell division by cross-linking DNA strands and decreasing DNA synthesis
It is a cell cycle phase nonspecific agent.

Potent immunosuppressive activity

Docetaxel:

Derived from the Yew tree (plant Alkyloid)
Binds to microtubules and results in inhibition of DNA, RNA, and protein synthesis

Occurs during the M phase of the cell cycle

GnRH agonists:

Ex Goserelin is a synthetic analog of luteinizing-hormone-releasing hormone (LHRH) testosterone level drops in blood - comparable to surgical castration.

SF133

New era: targeted therapy

Less toxic to host

Two classes:

1. Monoclonal antibodies
   Target cell surface proteins, growth factors or growth factor receptors
2. Small Molecules
   Tyrosine kinase inhibitors

Ex: Erlotinib (Tarceva)

Active in Non-small cell lung cancer and pancreatic cancer
Mechanism of action: targets and inhibits a tyrosine kinase pathway of a specific epidermal growth factor receptor over expressed on certain malignant cells

SF181

Lifetime risk of a cancer diagnosis:

Random Cancer Stats:

• 40% for women
• 45% for men
• 1 in 4 Canadians will die from cancer

Men:

Incidence = 1. Prostate, 2. Lung, 3. Colorectal

Death = 1. Lung, 2. colorectal, 3. Prostate

Women:

Incidence = 1. Breast, 2. Lung, 3. Colorectal

Death = 1. Lung, 2. Breast, 3. colorectal