Estimation and diagnosis of cancer

1- Clinical suspition:hematuria, rectal bleeding, mole that changes in size or color, a wound that fails to heal....

2- Clinical history: –genetics,

–social history as smoking,

–occupational history: miner,

–Diet and Geographic origin: smoked fish, hepatitis B.

–Sexual and child bearing history.

Estimation and diagnosis of cancer

3-Physical examination and Investigations:

When symptoms and signs associated with cancer

first appear, the disease is usually already at

advanced stage.

Routine (screening) examinations:

Pap smear, regular breast examination and

Mammography (each 2-3 years) after 40 years, ….

After 50 years, sigmoidoscopy every 3-5 years..

Laboratory, X ray, endoscopy.

4-cytologic diagnosis:

1-exfoliated cells: sputum, urine, CSF, body

fluids, blood, bone marrow smears.

2-brushing or scraping of epithelium or of a

lesion that has been seen by endoscopy

(bronchoscopy, gastroscopy, colposcopy)

Including Pap smear.

3-FNA (CT sacan and ultrasonography may

help guide the needle in to the mass.

5- Histopathology:

Biopsy: incisional, excisional

Information provided by biopsy:

type of tumor, biology, degree of invasion

(melanoma, TCC of bladder), grading and staging.

If there is not conclusive diagnosis, immunohistology, special stains, and electrone

microscopy.

Serologic diagnosis and follow up:

Hepatoma, Yolk sac T. alfa fetoprotein

(AFP)

Chriocarcinoma à hCG, control treatment.

Gastrointestinal tract ca. Esp. colon à CEA

Ovarian ca. à CA-125

Myeloma, some B cell lymphomas à

Monoclonal immunoglobulin

Prognosis of cancer

1-type of tumor

2-location

3-early diagnosis and staging

4-age and state of patient (breast cancer

and pregnancy..)

5-rate of growth

6-grading

7-sensitivity to radiation

• Treatment of Neoplasms

• Surgery

• Wide local excision

• Lymph node removal

• Surgery for metastatic disease

• Palliative surgery

• Radiation therapy:

• X ray (electromagnetic radiations of zero mass and

charge) = Gamma rays (radioactive isotopes)

• Chemotherapy:

• Cyclophosphamide, Chlorambucil, Methotrexate, Mercaptopurine…

• Immunotherapy

• Chemotherapy

• Began in 1943 (observation of Leukopenia after exposure to mustard gas….→ IV → dramatic but short lived responses in Lymphoma and Leukemia.

• When single agent → drug resistance →combination chemotherapy.

• Chemoth. May be prior to surgery to facilitate resection and prevent metastasis or after surgical debulking (adjuvant).

• Value of chemoth.. In improving the quality of life of patients, by palliating symptoms and pain, even in the absence of survival advantage, is evident.

• Responsiveness in decreasing order of efficacy:

• Category 1: germ cell, Leukemias, Lymphomas,

Choriocarcinoma.

• Cat. 2: Breast, Colorectal, Ovarian,

Osteosarcoma, Ewing’s,, Wilms T.

• Cat. 3: Lung, Bladder, Prostate, stomach,

Cervical.

• Cat. 4: Head and neck

• Cat. 5: Liver, Melanoma, Pancreatic, Brain,

renal, Thyroid.

• Cat. 1:

• use of a single or a combination of drugs used alone or with other therapeutic modalities will result in cure as defined by a normal life span in some and prolongation of survival in most patients.

• Cat. 2:

• survival is prolonged when chemoth. Is used as an adjuvant to local surgery or radiotherapy in the early stages of disease.

• Cat. 3:

• Single drug or combination will produce clinically usefull responses in more than 20% of patients. Prolongation of survival occurs in most responding patients but may be of short duration.

• Cat. 4:

• T. where local control may be improved by using

chemotherapy before or after surgery and

radiotherapy.

• Cat. 5:

• T. for which there are currently no effective drugs.

Objective response occur in less than 20% of

patients and there is no evidence of survival benefit

in randomized controlled trials when compared to best supportive care.

• Systemic effects of chemotherapy:

• 1-bone marrow suppression

• 2-intestinal ulceration

• 3-loss of hair

• 4-inhibition of germ cell development

(spermatozoa,.. oocytes…)

• 5-cessation of ovarian function

• 6-Nausea and vomiting

• 7-Mutation …-→ malignancy,… Leukemia..

• Drugs for supportive care:• Most effective cancer chemotherapy has

significant side effects.

• Antiemetics,

• Neutropenia and risk of infection is one of the most common dose-limiting side-effects of cancer chemotherapy, leading to reduced dosage, dilayed cycles and reduced effectiveness.

• Drugs for the relief of many symptoms (Opioid analgesics)…

• Immunotherapy• Treatment of cancer with Vaccines to stimulate

the host’s owns immune system to reject the

cancer has been a goal of tumor immunologists

for much of the 20th century..

• Apart from vaccines and administration of other

agents such as bacterial products, which

constitute Active immunotherapy, exogenous

immunity may be provided by the giving of

antibodies or lymphoreticular cells in Passive

immunotherapy.

• Progress has been substantial but there is

still a long way to go before Immunotherapy

is accepted as an important modality in the

treatment of cancer.

• The problems largely stem from the fact that

most cancer antigens (proteins displayed on the tumor

cell surface which elicit a response from the host immune system)

are also expressed in normal tissue, albeit

at different levels or developmental stages

(reappearance of AFP and CEA).

• This lack of “foreigness” has meant that

immunization against tumors has proved

difficult.

• It is also clear that the method by which the

antigen is presented to the immune system is

critical in that T-cells can be “tolerized” to

the tumor antigen, rather than activated.

• Immune responses can be qualitatively

different and vary in their ability to reject

tumors.

• Products of the tumor cell may have direct

suppressive effects on immune

responses.

• Certain tumor cells also appear resistant

to programmed cell death induced by

the immune cells.

• Sensitivity of tumors to irradiation

• 1-tissue of origin.

• 2-degree of differentiation, usually inversely propotional to

the sensitivity.

• 3-Mitotic activity, directly propotional to to the sensitivity.

• 4-Vascularity of the stroma and general blood supply.

• 5-Hypoxia reduce the sensitivity of tumors to radiation, conversely hyperbaric Oxygen has been used to enhance radiotherapy.

• 6- Recurrent tumors are insensitive.

• High radiosensitivity:

• Rapid cell turnover is characteristic of the

hair follicles, gastrointestinal tract, bone

marrow, lymphoid system, and germ cells.

• Acute radiation sickness, thus, results in

hair loss, nausea, vomiting, diarrhea, and

susceptibility to bleeding and infection.

• Low radiosensitivity:• The cells of certain organs (kidney, liver,

pancreas) and tissues (mature cartilage, muscle) rarely divide and are, thus relatively less affected by radiation. Gradual loss of function may result when such organs are within a therapeutic radiation field.

•

• Intermediate radiosensitivity:• Most other body tissues (.. connective

tissue, vessels, urothelium..).