Askep ca colon inggris
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Colorectal Cancer (CRC)
1) Epidemiology, Risk Factors
2) Symptoms, Stages, Therapy
3) Molecular Biology & Pathology
4) Screening
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EPIDEMIOLOGY
one of the most common cancers in the world
US: 4th most common cancer (after lung, prostate, and breast cancers)
2nd most common cause of cancer death(after lung cancer)
2001: 130,000 new cases of CRC 56,500 deaths caused by CRC
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Typical sites of incidence and sympoms of colon cancer
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Risk factors for CRC
Age
Adenomas, Polyps
Sedentary lifestyle, Diet, Obesity
Family History of CRC
Inflammatory Bowel Disease (IBD)
Hereditary Syndromes(familial adenomatous polyposis (FAP))
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result of interplay between environmental and genetic factors
Central environmental factors:
diet and lifestyle
35% of all cancers are attributable to diet
50%-75% of CRC in the US may be preventable through dietary modifications
Development of CRC
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consumption of red meat
animal and saturated fat
refined carbohydrates
alcohol
increased risk
Dietary factors implicated in colorectal carcinogenesis
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dietary fiber
vegetables
fruits
antioxidant vitamins
calcium
folate (B Vitamin)
decreased risk
Dietary factors implicated in colorectal carcinogenesis
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Symptoms associated with CRC
weight loss
loss of appetite
night sweats
fever
rectal bleeding
change in bowel habits
obstruction
abdominal pain & mass
iron-deficiency anemia
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TNM system
Primary tumor (T)
Regional lymph nodes (N)
Distant metastasis (M)
Staging of CRC
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Staging of CRC
A Mucosa 80%B Into or through M. propria 50%C1 Into M. propria, + LN ! 40%C2 Through M. propria, + LN! 12%D distant metastatic spread <5%
Dukes staging system
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Sites of metastasis
Liver
Lung
Brain
Bones
Via blood
Lymph nodesAbdominal wall
Nerves
Vessels
Via lymphaticsPer continuitatem
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Therapy
Surgical resection the only curative treatment
Likelihood of cure is greater when disease isdetected at early stage
Early detection and screening is of pivotalimportance
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Screening
What is screening?
a public health service in which members of a defined population are examined to identify those individuals who would benefit from treatment
to benefit: to reduce the risk of a disease or itscomplications
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fecal occult blood test (FOBT)chemical test for blood in a stool sample. annual screening by FOBT reduces colorectal cancer deaths by 33%
Flexible sigmoidoscopy can detect about 65%–75% of polyps and 40%–65% of colorectal cancers. rectum and sigmoid colon are visually inspected
Types of Screening
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regular screening for all adults aged 50 years or older is recommended
FOBT every year
flexible sigmoidoscopy every 5 years
total colon examination by colonoscopy every 10 years or by barium enema every 5–10 years
Current Screening Guidelines
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Changes resulting in colon cancer
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Molecular Biology & Pathology
CRCs arise from a series of histopathological and molecular changes that transform normal epithelial cells
Intermediate step is the adenomatous polyp
Adenoma-Carcinoma-Sequence (Vogelstein & Kinzler)
Polyps occur universally in FAP, but FAP accounts for only 1% of CRCs
Adenomatous Polyps in general population:33% at age 5070% at age 70
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Mutations in the APC pathway cause increased proliferation
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MMR defects give rise to TGF-beta RII mutations, which preventcell cycle inhibitor (p15) and protease inhibitor (PAI-1) expression
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Cyclooxygenase (COX)
cell membrane lipids
arachidonic acid (aa)
prostaglandins
Phospholipase A2
COX-1
-2
aspirinibuprofenindomethacin
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COX and CRC
COX-2 not detectable in normal colon but in 90% of CRCs and 40% of adenomas
Animal models: COX-inhibition results in 50% reduction of carcinomas and >90% reduction of adenomas
Epidemiological studies: patients regularly taking aspirin showed 40-50% reduced risk of CRC
But: minimal effective dose and duration of treatmenthave not yet been determined
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Microenvironment
Control mechanisms of mitosis & apotosis lost
High metabolic rates, glycolysis (Warburg),high lactic acid output
Result: hostile microenvironmental conditions(Hypoxia, low pH, low glucose, free oxygen radicals)
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Hypoxia
Central factor for tumor growth and spread
Correlated to tumor hypoxia:Therapy outcome & probablility of metastasis
Hypoxia exerts selective pressuregenetic instability results in survival of cellsbetter adapted to lack of oxygen
Evolution of highly aggressive tumor cells
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“Sign up to receive an e-mail message reminding you to have your colon screened at www.wewantthebestforyou.com”
CRC and the Internet
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CRC is a leading cause of death
Early stages are detectable
Screening can prevent CRC
Katie Couric: http://www.nccra.com/about/videos.htm
Summary