21st lecture (epidemology of cancer)

Question 1

how many people die from cancer per year?

Answer 1

10 million. (20% of the worlds death is caused by cancer)

Question 2

Describe the distribution of cancer by gender?

Answer 2

MALE: mortality rate:
#1: prostate cancer
#2: lung cancer
#3: GI cancer
FEMALE: morbidity:
#1: breast
#2: lung
#3:GI tract

Question 3

Describe the distribution of the different cancers over years?

Answer 3

Lung cancer increased in the 50s and then declined in both genders 20 years later, it was related to smoking.
Breast cancer experienced a small decline recently due to self-examination and education on the cancer. Mammography program where women over 50 are checked.
Prostate cancer is prominent over the age of 70. its decreasing because of effective cancer treatment but increasing as the population ages.
Stomach cancer decreased from the 50s at a rapid rate, due to refrigeration replaced smoking of food for preservation. The smoke was cancerous.
Cororectal experienced a slight decrease in recent years.

Question 4

Describe the distribution of cancer by age?

Answer 4

There of 2 peaks of cancer: 1 in childhood at the age of 2-5 and the other is at 60-70 years.
The type of cancers are different; The younger cancers are related to the still developing cancers. At old age the accumulation of mutation in cells causes cancer.

Question 5

Describe the distribution of cancer by geographic location?

Answer 5

In japan the smoked fish causes stomach cancer
In india: oral cancer is common
In asia: nasopharyngeal carcinoma

Environmental and genetic factors plays a role: Japanese that moved to America saw a decrease in the amount of stomach cancer.

hepatocellular cancer has increased in the developing world do to the infection of the virus.

Question 6

What are some of the environmental causes of cancer..

Answer 6

• alcohol causing: oral, pharyngeal, esophagus, stomach cancer, heptocellular cancer via the cirrhosis.
• smoking; oral pharyngeal, bronchial, lung cancer. (follows the route of the smoke).
• Obesity if related to colon cancer.

Question 7

describe carcinogenesis?

Answer 7

its a multistep process; certain sequence of mutations can generate cancer.
precancerous is related to dysplasia based on maturation.
Dysplasia can stay as it is with no alteration for a while as the carcinogen is eliminated. Or it can develop to cancer.

Anaplasia and dysplasia are synonyms.

Question 8

What are the Facultative preneoplastic stages?

Answer 8

These are factors that will say that the patient may or may not have cancer.

Question 9

what are the pre-neoplastic conditions.

Answer 9

1. persistent regeneration: a cell that dies and regenerates puts pressure on the mitotic activity possibly causing cancer, i.e. cirrhosis of the liver or paget’s disease (constant remodeling of the bone)
2. hyperplasia/metaplasia: (endometrium hyperplasia, or bronchial hyperplasia/metaplasia can lead to cancer).
3. Chronic inflammation; inflammatory reaction kills the cells as inflammatory cells release ROS. This is a genotoxic affect from the inflammatory cells. As the cells die the stems cells are pressured into proliferating. A genotoxic affect from one side and proliferation from the other side favors carcinogenesis. (examples: helicopylori gastritis)
4. Immune deficiency: (post transplant conditions) viral infection + immune deficiency causes cancer.
5. Autoimmunity: MALT lymphoma (active immune system may make mistakes causing cancer)
   6: Benign to malignant neoplasm

Question 10

Morphology of cancers? (intraepithelial neoplasm)

Answer 10

intraepithelial neoplasm: Basal cell layer - stratum planocellulare - stratum croneum layers from deep to superficial.
The basal cells may loose the differentiation and may start to take over the whole thickness of the epithelium. This is an intraepithelium neoplasm until they disrupt the basement membrane at which they are called cervical cancer.

Question 11

Morphology of cancers? describe how we judge the grade of a cancer? (intraepithelial neoplasm)

Answer 11

Thickness of the involved epithelium we speak about Cervical intraepithelial neoplasia (CIN1, CIN2, CIN3).
Depending on which part of the epithelium is replaced.
CIN1: 1/3
CIN2: 2/3
CIN3: 3/3
This is in the precancerous stage.
In clinical studies the prognosis of the CIN1, and CIN2 is the same, so new studies were needed:
LSIL: Low risk squamous intraepithelial lesions (CIN1, CIN2)
HSIL: High risk squamous intraepithelial lesions (CIN3)

This is important because if its diagnosed in the early stages a “cone resection” can be done, removing the diseased tissue to prevent cervical cancer.

Question 12

papanicolau test description?

Answer 12

swabbing the cervix and made a smear to analyze the cells. This swab reflects what is happening on the surface of the cervix:
P1: Normal (hormonal active lady)
P2: Normal (inactive)
P3: Unknown (could be normal or neoplastic)
P4: Dysplasia
P5: Neoplasia

This reduced cervical cancer death to near zero if the lady goes for screening every year. Since the screening can lead to cone-resection if its a dysplasia. Today the treatment is more complex.
PCR HIV examination can lead to the cervical examination and they to cone-resection and treatment.

Women if active sexual life have to be screened every year, Cancer development can take years as its a multi step process. HPV vaccine can also be used since cervical cancer can be related to HPV infection.

Question 13

Describe the meaning of the following:
Pan IN 
VAIN
PIN 
DIN
MDS

Answer 13

Pan IN (pancreas in-situ neoplasia)
VAIN (vaginal in-situ neoplasia). 
PIN (Prostate in-situ neoplasia)
DIN (ductal (breast) in-situ neoplasia)
MDS (myelodysplastic syndrome) = immune cells do not mature properly.

Question 14

What is leukoplakia?

Answer 14

white or grayish patches form usually inside your mouth. Smoking is the most common cause. But other irritants can cause this condition as well. Mild leukoplakia is usually harmless and often goes away on its own.

It could be due to inflammation, hyperplastic, dysplastic. If its not treated with conservative treatment then a biopsy must be performed.
All preneoplastic disease are diagnosed vis microscopy.

Question 15

Describe the grading and staging of cancers?

NOTE: there are 2 questions for cancer:

1. how to treat it?
2. what is the prognosis?

Answer 15

Grading: histology classification; how much of the tumor cells are anaplastic, how much have they de-differentiated. Tumor cells could be very similar to the normal tissue and thus a grade 1. High level of differentiation it could be grade 4 or 5. (this classification is subjective and is very hard to reproduce).
STAGING: the extension of the tumor/size of the tumor is graded via T1 - T4.
-metastasis is graded via N0 - N1 (lymph Node metastasis) Nx = unknown
-Distant metastasis is graded via: M0 - M1. Mx = unknown.

Question 16

Describe how the tumor size T1-T4 classification works for cancers. (colon cancer as an example).

Answer 16

Mucous membrane has the following layers:

• Mucosa
• Muscularis mucosa
• Submucosa
• muscularis propria/lamina propria,
• Peritoneum

Cancer extends to the mucosa = T1
Submucosa = T2
lamian propria = T3
Passes the peritoneum = T4.

Question 17

How do we classify the stage of a cancer using the T,N,M system for staging?

Answer 17

Stage 1: T1-T2, N0, M0 (98% survival)
Stage 2: T3-T4, N0, M0 (80-90% survival)
Stage 3: T1-T4, N1, M0 (40-50% survival)
Stage 4: T1-T4, N0-N1 and M1 (8% survival)

Survival = 5 year survival rate.

Question 18

Describe the affects of the tumor on the organism?

Answer 18

2 types of affects:
A/ Local growth of tumor: related to bleeding (tumor may disrupt the vascular system. Its also related to inflammation as the epithelium immune defense is disrupted making the organism prone to infection. The 3rd if Necrosis: the tumor grows faster then the stroma.
B/ Systemic affects: 3 categories:
1. Endocrine tumor
2. Cahexia
3. paraneoplastic syndrome

Question 19

Describe the endocrine, systemic tumor affect on patients?

Answer 19

Endocrine tumor: humeral affects: i.e. pheochromocytoma (adrenal medulla cancer): leading to hypertension do to catecholamines. Or can be for thyroid cancer.

Question 20

Describe the cahexia, systemic tumor affect on patients?

Answer 20

generalized atrophy of the patient, weakness, low muscle force. Related to TN-aplha secreted by the neoplastic cells and inflammatory cells co-ordinated by the neoplastic cells; They affect the metabolism of patients; they inhibit lipoprotein lipase and thus lipids are mobilized. they also inhibit the release of fatty acids.

Cachexia induces the cytokines, in particular tumor necrosis factor (TNF)-α, IL-1, is thought to inhibit the activity of lipoprotein lipase (LPL), and thereby induces weight loss as a result of reduced fat accumulation in the tissues.

Question 21

Describe the paraneoplastic syndrome, systemic tumor affect on patients?

Answer 21

wide range of symptoms that tumor cells generate depending on what soluble factors or hormones that they release.

1. endocrinopathies: Tumors that are no endocrine tumors can be humorally active. Cushings syndrome (ACTH secreted via lung cancer, or pancreas cancer) Hypercalcemia do to high PTH. Hypoglycemia do to insulin release.
2. Skin affects: acanthosis nigricans; grey-brown hyperkeratotic swelling on the skin (excessive epidermal growth factors secreted by the cancer.)
3. Blood coagulation affects: migratory thrombophlebitis (Trousseau syndrome); vein thrombosis in different areas do to the hypercoagulability of the patient as the cancer develops pro-coagulability factors.
4. Cardian: marantic endocarditis: The mitral valve has small vegetations made of fibrin and platelets.
5. Neuropathies: i.e. myasthenia gravis: weakness of muscle.