Subject: Surgery Topic: Principles of Surgical Oncology Lecturer: Dr. Malen M.

Gellido Date of Lecture: 22 July 2011 Transcriptionist: Gluttonoids Pages: 13

THE ROLE OF SURGERY IN CANCER MANAGEMENT

Cancer Statistics - according to the International Agency for Research on Cancer, WHO (2008) Most Frequent Cancers in the world: Female: Incidence Mortality 1. 2. 3. 4. 5. 6. 7. 8. 9. 10. Male: Incidence 1. Lung 2. Prostate 3. Colorectum 4. Stomach 5. Liver 6. Esophagus 7. Bladder 8. Non-Hodgkin Lymphoma 9. Leukemia 10. Others Both sexes: Incidence: 1. Breast 2. Prostate 3. Lung 4. Colorectum 5. Cervix Uteri 6. Stomach 7. Liver 8. Corpus Uteri 9. Esophagus 10. Ovary Mortality 1. Lung 2. Prostate 3. Colorectum 4. Stomach 5. Liver 6. Esophagus 7. Leukemia 8. Bladder 9. Non-Hodgkin Lymphoma 10. Others Breast Colorectum Cervix Uteri Lung Stomach Corpus Uteri Liver Ovary Thyroid Others 1. Breast 2. Colorectum 3. Cervix Uteri 4. Lung 5. Stomach 6. Liver 7. Ovary 8. Corpus Uteri 9. Thyroid 10. Others

Most Frequent Cancers in the Philippines: Female: Incidence Mortality 1. Breast 1. Breast 2. Cervix Uteri 2. Lung 3. Lung 3. Cervix Uteri 4. Colorectum 4. Liver 5. Ovary 5. Colorectum 6. Liver 6. Ovary 7. Corpus Uteri 7. Leukemia 8. Thyroid 8. Stomach 9. Leukemia 9. Corpus Uteri 10. Stomach 10. Thyroid Male: Incidence Lung Liver Prostate Colorectum Stomach Leukemia Pharynx, Others 8. Brain 9. Non-Hodgkin Lymphoma 10. Lip/Oral Cavity 1. 2. 3. 4. 5. 6. 7. Both sexes: Incidence: 11. Breast 12. Lung 13. Cervix Uteri 14. Liver 15. Prostate 16. Colorectum 17. Ovary 18. Stomach 19. Corpus Uteri 20. Leukemia Mortality Lung Liver Colorectum Prostate Stomach Leukemia Brain Pharynx, Others 9. Non-Hodgkin Lymphoma 10. Lip/Oral Cavity 1. 2. 3. 4. 5. 6. 7. 8. Mortality 11. Lung 12. Breast 13. Liver 14. Cervix Uteri 15. Prostate 16. Colorectum 17. Stomach 18. Leukemia 19. Ovary 20. Brain

Mortality 1. Lung 2. Breast 3. Stomach 4. Liver 5. Colorectum 6. Cervix Uteri 7. Prostate 8. Esophagus 9. Ovary 10. Leukemia

Incidence Rate of Neoplasms Malignant Neoplasms ranked number 3 in the over-all cause of morbidity in 2005 - Causes of death in the Philippines as of 2005 (DOH): 1st and 2nd =Cardiovascular disease 3rd = Malignant Neoplasms

SY 2011-2012

CARCINOGENESIS
The Cell Cycle

During the synthetic or S phase, the cell generates a single copy of its genetic material,. Mitotic or M phase, the cellular components are partitioned between two daughter cells. The G1 and G2 phases represent gap phases during which the cells prepare themselves for completion of the S and M phases, respectively. When cells cease proliferation, they exit the cell cycle and enter the quiescent state referred to as G0. In human tumor cell-cycle regulators like INK4A, INK4B, and KIP1 are frequently mutated or altered in expression. These alterations underscore the importance of cell-cycle regulation in the prevention of human cancers.

local selection pressures such as hypoxia. Apoptosis is a genetically regulated program to dispose of cells. o Cancer cells must avoid apoptosis if tumors are to arise. o The growth of a tumor mass is dependent not only on an increase in proliferation of tumor cells but also on a decrease in their apoptotic rate. Metastases arise from the spread of cancer cells from the primary site and the formation of new tumors in distant sites. A feature of malignant cells is their ability to invade the surrounding normal tissue. The ability to invade involves o changes in adhesion, o initiation of motility, and o proteolysis of the extracellular matrix (ECM).

Oncogenes

Six Essential Alteration in Cell Physiology that Dictate Malignant Growth 1. 2. 3. 4. 5. 6. Self- sufficiency in growth signals Insensetivity to antigrowth signals Tissue invasion and metastasis Limited replicative potential Sustained angiogenesis Evading apoptosis

counterpart: Proto-oncogenes they are originally proto-oncogenes that become abnormal through mutation, chromosomal transfer, or amplification These are: o PGFR (growth factor) o HER 2 neu (growth factor receptor) o c-myc (nuclear transcription factor) o ras (intracellular signal transduction molecules) Tumor supressor genes (mutations in these genes leads to cancer): o RB1 o p53 o APC o BRCA 1 and 2- breast cancer genes

FACTORS AFFECTING CARCINOGENESIS

A. Genetic Factors (See Last Page for table) General Features of Hereditary Cancer Syndromes Same or linked forms of cancer in two or more close relatives Earlier than usual cancer onset in one or more relatives Bilateral cancer in paired organs Multiple primary tumors in the same individual Specific constellation of tumors are part of known cancer syndrome Evidence of autosomal dominant transmission of cancer susceptibility

**Remember SALISE in patho. Self sufficiency in growth signals Ability to invade and metastasize Limitless replicative potential Insensitivity to growth-inhibitorysignals Sustained angiogenesis Evasion of APOPTOSIS Angiogenesis is the establishment of new blood vessels from a pre-existing vascular bed which is essential for tumor growth and metastasis. Tumors develop an angiogenic phenotype as a result of accumulated genetic alterations and in response to

B. Chemical Factors o even chemotherapic agents can cause malignancies. o chemical carcinogens usually affect specific organs, targeting the epithelial cells (or other susceptible cells within an organ) and causing genetic damage (genotoxic) o the most commonly associated exposures that increase cancer risk are: tobacco, alcohol, diet, and reproductive factors (e.g., sexual behavior and hormones). o Chemically related DNA damage and consequent somatic mutations relevant to human cancer can occur: Directy from exogenous exposures Indirectly activation of endogenous mutagenic pathways (e.g., nitric oxide and oxyradicals) Chemotherapeutic Agents

C. Viral Factors May cause or increase the risk of malignancy through: o direct transformation, expression of oncogenes that interfere with cellcycle checkpoints or DNA repair o expression of cytokines or other growth factors o alteration of the immune system. Oncogenic viruses may be RNA or DNA types

1. RNA Viruses Retroviruses that contain transcriptase.

reverse

After infection, the single-stranded RNA viral genome is transcribed into a double-stranded DNA copy, which is then integrated into the chromosomal DNA of the cell. Retroviral infection of the cell is permanent; thus integrated DNA sequences remain in the host chromosome

2. DNA Viruses Unlike the oncogenes of the RNA viruses, those of the DNA tumor viruses are viral, not cellular, in origin. These genes are required for viral replication using the host cell machinery. In permissive hosts, infection with an oncogenic DNA virus may result in a productive lytic infection, which leads to cell death and the release of newly formed viruses. In nonpermissive cells, the viral DNA can be integrated into the cellular chromosomal DNA, and some of the early viral genes can be synthesized persistently, which leads to transformation of cells to a neoplastic state. The binding of viral oncoproteins to cellular tumor-suppressor proteins p53 and Rb is fundamental to the carcinogenesis induced by most DNA viruses, although some target different cellular proteins.

Biological Agents that Cause Carcinogenesis

** how radiation produce cancer all the things are on the molecular level 2. UV Rays UV light creates UV-specific dipyrimidine photoproducts in the DNA of the target cells. When these are not sufficiently repaired, errors in replication can result in characteristic mutations in critical genes.

D. Physical Factors 1. Radiation Damage nucleotides, cross linkage, DNA single and double stranded breaks, inactivates tumor suppressor gene, induces genomic instability in cells that persist at least 30 generations Induces DNA lesions that damage nucleotide bases and cross-linking, and DNA single- and double-strand breaks (DSBs). Misrepaired DSBs are the principal lesions of importance in the induction of chromosomal abnormalities and gene mutations. DSBs in irradiated cells are repaired primarily by a nonhomologous endjoining process, which is error prone; thus DSBs facilitate the production of chromosomal rearrangements and other large-scale changes such as chromosomal deletions. It is thought that radiation may initiate cancer by inactivating tumorsuppressor genes. Radiation induces genomic instability in cells that persists for at least 30 generations after irradiation. Therefore, even if cells do not acquire mutations at initial irradiation, they remain at risk for developing new mutations for several generations.

3. Asbestos Asbestos is a naturally occurring mineral silicone that results from fibrous crystallization Induce DNA damage, including DSBs, mutations, and chromosomal damage. Asbestos fibers can impair mitosis and chromosomal segregation, which can result in aneuploidy. Due to formation of reactive oxygen species Can cause Mesothelioma

o Needle aspiration biopsy o Aspiration biopsy o Aspiration cytology o Needle biopsy Equipment needed: o 10 or 20ml syringe o Gauge 21- 27 needle **In a cell cycle, there are a lot of checkpoints but if tumor suppressor genes/oncogenes enter the cycle they will bypass the checkpoints, causing a lot of mutations and later on they will become cancer. (see last page for larger picture) o Glass slides o Local anesthetic Where is it done? o Office or clinic Advantages: o Office procedure o Cheap o Fast o High sensitivity Disadvantages: o Needs experienced cytopathologist o Low specificity o Can not distinguish invasive from in-situ malignancies 2. Core Needle Biopsy Performed with a large cutting needle, usually 14 gauge, deployed into the area of concern by a rapid-fire, springloaded, automated instrument. Retrieves a small piece of intact tumor tissue, which allows the pathologist to study the invasive relationship between cancer cells and the microenvironment. Advantages: o Sampled material familiar to most pathologists o Insufficient sampling infrequent (<1%) o Can differentiate invasive from in-situ cancer o No scar Disadvantages: o More expensive than FNAB o Less specificity than excision biopsy OPEN SURGICAL BIOPSY Other related terms: o Fine needle cytology o Fine needle biopsy 1. Incision Biopsy Removal of a portion of tumor through an actual incision through the skin or from the fungating tumor itself

SURGERY IN CANCER MANAGEMENT

DIAGNOSIS OF CANCER Biopsy An examination of tissue removed from a living body in order to determine the presence or extent of a disease. Origin 19th century French from Greek bios (life) and opsis (sight) Types of Biopsy Needle Biopsy - Fine Needle - Core Needle Open Surgical Biopsy - Incision Biopsy - Excision Biopsy NEEDLE BIOPSY 1. Fine Needle Aspiration Biopsy A cytologic technique in which cells are aspirated from a tumor using a needle and syringe with the application of negative pressure. Aspirated tissue consists of disaggregated cells rather than intact tissues

Used for tumors that are too big to be removed in its entirety without doing major surgery Examples: o Portions of tumor taken during endoscopic examinations of the bronchus, esophagus, stomach, duodenum, colon and rectum o Endometrial curettage

o Diagnostic and therapeutic (sometimes) Disadvantages: o Invasive procedure o Scar formation o Most expensive o Needs heavy sedation, even general anesthesia o Done in the operating room

2. Excision Biopsy An excision of the entire suspected tumor tissue with little or no margin of surrounding normal tissue is performed Excisional biopsy is the procedure of choice for most tumors if it can be performed without contaminating new tissue planes or further compromising the ultimate surgical procedure Can be both diagnostic and therapeutic Guiding Principles in Biopsy Procedures 1. Needle tracks or scars should be placed carefully so that they can be conveniently removed as part of the subsequent definitive surgical procedure. 2. Care should be taken to avoid contaminating new tissue planes during the biopsy procedure. 3. Adequate tissue samples must be obtained to meet the needs of the pathologist. 4. When knowledge of the orientation of the biopsy specimen is important for subsequent treatment, the surgeon should mark distinctive areas of the tumor carefully to facilitate subsequent orientation of the specimen by the pathologist. 5. Placement of radiopaque clips during biopsy and staging procedures is sometimes important to delineate areas of known tumor and to guide the subsequent delivery of radiation therapy to these areas. Biopsy Techniques FNA Office procedure Hemorrhage Wide sampling Ease of interpretation Ability to detect invasion Cost Rapid diagnosis Yes + + + No + +++

When is it done? o Needle biopsy not feasible o Prior biopsy results are nondiagnostic o Prior biopsy results are discordant with clinical findings

Where is it done? o Usually in the operating room Other examples: o Polypectomy (during colonoscopy) o Removal of skin lesions o Hemithyroidectomy

Core biopsy Yes ++ ++ ++ Yes ++ ++

Excision No ++ +++ +++ Yes +++ +

Advantages: o Allows pathologist to examine the entire lesion o Near 100% diagnostic accuracy o Can distinguish invasive from insitu cancer

HOW WILL YOU BIOPSY NON-PALPABLE LESIONS? Pulmonary nodule

2. Vacuum-assisted biopsy device (Mammotome Stereotactic or ultrasound guidance) Inserted once and rotated while in the breast to obtain samples from different areas of the lesion. A vacuum is used to pull tissue into the sample notch and transported to the collection chamber

Retroperitoneal mass

Image-guided biopsy for non-palpable lesions of the breast Stereotactic guidance Ultrasound guidance Magnetic resonance imaging guidance Needle localization biopsy A. Stereotactic Guidance

Using the vaccum-assisted breast biopsy system, the probe is positioned at the lesion. It vacuums, cuts, and removes tissue samples, which are passed through the probes hollow chamber into a collection tray. This allows for multiple samples to be collected whole only one incision into the breast is made.

Mammographic Needle Localization

Uses the principle of parallax to determine the lesion position in 3-D space Two angled xray views (stereotactic pair) acquired with the beam 15 degrees on either side of the center are used to localize the mammographic lesion A computer algorithm /software is used to calculate the position of the lesion

Cranio-caudal view

Magnification Micro calcifiview cations localized by needle

Mammographic Needle Localization Biopsy

1. Automated core biopsy guns Multiple core biopsy samples are necessary to ensure accurate sampling May need 5 -10 samplings Require multiple needle insertions

Specimen Mammography Excised breast tissue with needle intact is radiographed Mammographic abnormalities should be included in the specimen

Tis

Lobular carcinoma in situ

Tis Pagets disease of the nipple with no tumor. T1: T1a: T1b: T1c: T2: T3: Tumor < 2.0 cm or less Tumor 0.1 cm 0.5 cm Tumor 0.5 cm 1.0 cm Tumor 1.0 cm 2.0 cm Tumor 2.0 cm 5.0 cm Tumor > 5.0 cm T1mic: Microinvasion < 0.1 cm

Not all tumors need to be biopsied prior to surgical removal Parotid neoplasms Tumors of the head of the pancreas or periampullary area causing obstructive jaundice Liver tumors Retroperitoneal tumors **Biopsy may be omitted in situations whereby the histopath result will not change the decision to operate and surgically remove a tumor Biopsy is mandatory to establish the presence of malignancy in Patients who have inoperable tumors and need to undergo systemic anticancer treatment (chemotherapy, targeted therapy, etc) or radiation therapy.

T4: Tumor of any size with direct extension to chest wall or skin T4a: Extension to chest wall, not including pectoralis muscle T4b: Edema (including peau dorange) or ulceration of the skin of the breast or satellite skin nodules confined to the same breast T4c: T4d: Both T4a and T4b Inflammatory carcinoma.

Clinical Nodal Staging NX: Regional lymph nodes cannot be assessed N0: No regional lymph node metastasis N1: Metastasis to movable ipsilateral axillary lymph node(s) N2: Metastasis in ipsilateral axillary lymph node(s) fixed or matted, or in clinically apparent ipsilateral internal mammary nodes in the absence of clinically evident axillary lymph node metastasis N3: Metastasis in ipsilateral infraclavicular lymph node(s) with or without axillary lymph node involvement, or in clinically apparent iipsilateral internal mammary lymph node(s) and in the presence of clinically evident axillary lymph node metastasis; or metastasis in ipsilateral supraclavicular lymph node(s) with or without internal axillary or mammary lymph node involvement

CANCER STAGING
Why is cancer staging needed? To be able to prognosticate To be able to choose the appropriate management

Staging Systems Which staging system to use depends on the type of malignancy AJCC/UICC uses TNM and is the most commonly used for almost all solid tumors FIGO preferred by gynecologists Other systems for hematologic malignancies

Pathologic Nodal Staging pNX: Regional lymph nodes cannot be assessed pN0: No regional lymph node metastasis pN1: Metastasis in 1 to 3 axillary lymph nodes

Clinical Tumor Signaling TX: T0: Tis: Tis Primary tumor cannot be assessed No evidence of primary tumor Carcinoma in situ Ductal carcinoma in situ

pN2: Metastasis in 4 to 9 axillary lymph nodes pN3: Metastasis in 10 or more axillary lymph node

Distant metastasis MX: Presence of distant metastasis cannot be assessed M0: M1: No distant metastasis Distant metastasis present

Breast Cancer 5 Year Survival Rates Stage I 94% Stage IIa 85% Stage IIb 70% Stage IIIa 52% Stage IIIb 48% Stage IV 18%

TREATMENT OF CANCER
1. Removal of primary tumor provides local and regional control of the malignant process. Local tumor itself with margin of normal tissue Regional draining lymph nodes Questions before surgery Is there informed consent? Discuss risks and benefits Will the patient tolerate the procedure? Presence of co-morbid factors Nutritional status Performance status Curative or palliative? COLON CANCER

Cancer Staging Metastatic work-ups, usually in the form of imaging studies, are done to determine the presence of distant spread. Distant spread is defined by the staging system Usually refers to any area beyond the regional lymph node groups AJCC Stage Groupings for Breast Cancer STAGE TUMOR NODE METASTASIS 0 Tis N0 M0 I IIA T1 T0 T1 T2 IIB T2 T3 T0 T1 IIIA T2 T3 T3 IIIB IV T4 Any T Any T N0 N1 N1 N0 N1 N0 N2 N2 N2 N1 N2 Any N N3 AnyN M0 M0 M0 M0 M0 M0 M0 M0 M0 M0 M0 M0 M0 M1

**The lymphatic drainage of lesions in various anatomic locations throughout the colon.

Diagnostic Studies for Breast Cancer Patients Cancer Stage 0 I II III IV History & physical X X X X X CBC, platelets X X X X Liver function tests X X X X Chest x-ray X X X X Bilateral mammograms X X X X X Hormone-receptor X X X X status HER2/neu expression X X X X Bone scan X X X Abdominal CT scan or X X ultrasound or MRI

Tumor A in the cecum or ascending colon. A -> A (left colon) local margin is followed on the surgical resection to satisfy the regional control (lymph nodes) which are found along the vasculature (right colon) Remember: o carcinoma epithelial in origin metastasizes through lymphatic system (lumph nodes). o Sarcoma - mesenchymal in origin metastized through hematogenous route

BREAST CANCER Modified Radical Mastectomy vs. Lumpectomy MRM Lumpectomy

Large incision is made Curvilinear or radial from axilla across the incision concentric to breast the nipple-areola complex Breast tissue is dissected Carcinoma and from pectoralis muscle surrounding tissue is and removed removed completely Large scar and absent Small scar after breast after operation operation MRM = Lumpectomy with axillary dissection + radiation Radiation is needed to sterilize the breast tissue that was left behind after the surgery Lumpectomy for lesser magnitude Has a high chance of recurrence but with same rate of survival with Total Mastectomy. Breast is kept

Wide resection Local control is used by excising the tumor surrounding the normal tissue, regional control is disregarded.

Stage III Locally Advanced Breast Cancer Preoperative Chemotherapy

Mastectomy or Breast Conversation Therapy (BCT) if possible pre operative chemotherapy is given before the surgery to shrink the tumor. If chemotherapy is given before the surgery there will be less recurrence and improved survival. But if chemotherapy is NOT given before the surgery there is a chance for an early recurrence.

SENTINEL LYMPH NODE BIOPSY

Used to determine the status of axillary lymph nodes without encountering the morbidities of doing full Axillary Lymph Node Dissection (ALND) usually performed before removal of the primary breast tumor ALND has complication like lymph edema (LE). To prevent LE, sentimental lymph node is taken out. Nuclear Dye is used to localized the sentinel lymph node.

Neoadjuvant chemotherapy

TREATMENT OF CANCER (cont.) 2. Cytoreductive Surgery In some instances, the extensive local spread of cancer precludes the removal of all gross disease by surgery.

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The partial surgical resection of bulk disease in the treatment of selected cancers improves the ability of other treatment modalities to control residual gross disease that has not been resected. Burkitt's lymphoma and ovarian cancer

3. Metastatic disease Removal of tumors that have spread to distant sites May lengthen a patients survival or even provide cure As a general principle, patients with a single site of metastatic disease that can be resected without major morbidity should undergo resection of that metastatic cancer 7. Therapies other than surgical therapy (read the book to know this nice to knows :p ) Chemotherapy (Pharma o_0) Hormonal Therapy Targeted Therapy Immunotherapy Gene Therapy Radiation Therapy (different lecture)

4. Oncologic Emergencies exsanguinating hemorrhage perforation drainage of abscesses impending destruction of vital organs obstruction

CANCER PREVENTION
Diet Lifestyle

5. Palliation Surgical resection often is required for the relief of pain or functional abnormalities. The appropriate use of surgery in these settings can improve the quality of life for cancer patients. Palliative surgery may include procedures to relieve mechanical problems, such as intestinal obstruction, or the removal of masses that are causing severe pain or disfigurement

Three Categories (not in the ppt but in the book) a. primary prevention b. i.e., prevention of initial cancers in healthy individuals i.e., prevention of cancer in individuals with premalignant conditions c. tertiary prevention i.e., prevention of second primary cancers in patients cured of their initial disease

secondary prevention

6. Reconstruction and Rehabilitation The ability to reconstruct anatomic defects can substantially improve function and cosmetic appearance Lost function (especially of extremities) often can be restored by surgical approaches. These includes lysis of contractures or muscle transposition to restore muscular function that has been damaged by previous surgery or radiation therapy

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Conditions in Which Prophylactic Surgery Can Prevent Cancer Underlying Condition Cryptorchidism Polyposis coli Familial colon cancer Ulcerative colitis Multiple endocrine neoplasia types 2 and 3 Familial breast cancer Familial ovarian cancer RECURRENCE Associated Cancer Testicular Colon Colon Colon Medullary cancer of the thyroid Breast Ovary Prophylactic Surgery Orchiopexy Colectomy Colectomy Colectomy Thyroidectomy

MULTIDISCIPLINARY APPROACH TO CANCER MANAGEMENT

Modern cancer therapy is multidisciplinary, involving the coordinated care of patients by:

Surgical Oncologist Medical Oncologist Radiation Oncologist Primary Care Physician Pathologist Gynecologic Oncologist Reconstructive surgeon Anesthesia/Pain Specialist Rehab Med Physician Radiologist Psycho Oncologist Palliative Care Specialist Nurse Oncologist Chaplain/ Pastoral Care Staff Hospice Care Staff Support Groups Family Members

Mastectomy Oophorectomy

CASE STUDY

60 y/o male, presenting with mass on his anterior neck

Diagnostic Procedures and Treatment: History & PE = Clinical diagnosis Imaging studies ( mammography +/ultrasound if breast cancer) Biopsy Stage the disease Definitive treatment Additional treatment Surveillance END OF TRANSCRIPTION

Metastases can sometimes arise several years after the treatment of primary tumors. o E.g breast cancer recurrences have been reported decades after the original tumor. Dormancy - cells remain viable in a quiescent state and then become reactivated by a physiologically perturbing event o Cells establish preangiogenic metastases in which they continue to proliferate but that proliferative rate is balanced by the apoptotic rate.

I consider that our present sufferings are not worth comparing with the glory that will be revealed in us. Romans 8:18
RT @medschooladvice: Memorize, take test, unload. Memorize, take test, unload. Med school: the bulimia of learning. ~follow him on twitter :p

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A GENETIC MODEL FOR COLORECTAL TUMORIGENESIS

A genetic model for colorectal tumorigenesis. (**useful to know. The diagram part was not discussed extensively) Tumorigenesis proceeds through a series of genetic alterations involving oncogenes and tumor-suppressorgenes. In general, the three stages of adenomas represent tumors of increasing size, dysplasia, and villous content. Individuals with familial adenomatous polyposis (FAP) inherit a mutation on chromosome arm 5q. In tumors arising in individuals without polyposis, the same region may be lost or mutated at a relatively early stage of tumorigenesis. A ras gene mutation (usually K-ras) occurs in one cell of a pre-existing small adenoma which, through clonal expansion, produces a larger and more dysplastic tumor. The chromosome arms most frequently deleted include 5q, 17p, and 18q. Allelic deletions of chromosome arms 17p and 18q usually occur at a later stage of tumorigenesis than do deletions of chromosome arm 5q or ras gene mutations. The order of these changes varies, however, and accumulation of these changes, rather than their order of appearance, seems most important. Tumors continue to progress once carcinomas have formed, and the accumulated chromosomal alterations correlate with the ability of the carcinomas to metastasize and cause death. DCC = deleted in colorectal cancer gene

Easter Cooperative Oncology Group: Performance Scale and Corresponding Karnofsky Rating Grade 0 1 2 3 4 Description Karnofscy Scale Fully active, able to carry on all predisease activitiease without restriction 100 Restricted in physically strenuous activity, but ambulatory and able to carry 80 90 out work of a light or sedentary nature (e.g., light houseworl/office work) Ambulatory and capable of all self-care but unable to carry out any work 60 70 activities; up and about more than 50% of waking hours Capable of limited self-care, confined to bed or chair 50% or more of 40 50 waking hours Completely disabled cannot carry on any self-care; totally confined to bed or chair 30 or less

***This was not emphasized by Dr. Gellido but is included in his ppt.

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**nasa libro itong table at nasa ppt din di doc...baka gusto nyong kabisaduhin.. Good luck! :p o But the genes he emphasized were RB1, p53, APC, BRCA 1 and 2

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