Transcript Colon Cancer

Colon Neoplasia
VALERIE P. BAUER, MD
DIVISION OF COLON AND RECTAL SURGERY
ASSISTANT PROFESSOR
DEPARTMENT OF SURGERY
UTMB GALVESTON
JUNE 8, 2011
Epidemiology
COMMON
INCREASING INCIDENCE
DECREASING MORTALITY
Epidemiology
 Third most common diagnosed cancer and cause of
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cancer death annually
1 million people develop CRC annually
150,000 cases will be diagnosed in US
Probability of individual developing CRC in US is %6
over a lifetime
Population risk factors
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Age
Ethnicity
Race
Socioeconomic status
Etiology
AGE
DIETARY
ENVIRONMENTAL
PREDISPOSING MEDICAL CONDITIONS:
PRIOR HISTORY COLON CANCER OR POLYPS
INFLAMMATORY
GENETIC
Dietary Risk Factors for CRC
 Saturated animal fat
 Red meat
 High in iron- a pro-oxidant
 May increase free radicals that damage mucosa
 Charbroiled meat contains aromatic hydrocarbons
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Increasing RM consumption by 3.5 oz/ day is associated with 1217% increased risk of CRC
 Fruit and vegetables
 Contain anti-oxidants
 Studies show no association between high fruit and vegetable
consumption and risk reduction for CRC
Dietary Risk Factors for CRC
 Fiber
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Conflicting data
Increases intestinal transit, decreases exposure to carcinogens
May dilute or absorb carcinogens
Beneficial effect on colon- not rectum
Prostate, Lung, Colorectal, and Ovarian Screening Trial
 European Prospective Investigation into Cancer and Nutrition
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 Calcium
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Binds and precipitates bile salts
Beneficial in two randomized double blind placebo controlled trials
1200mg/ day for 4 years
 2000mg/ day 3 years
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Dietary Risk Factors for CRC
 Folate (Vitamin B)
 Normal DNA methylation
 Folate deficiency may disrupt DNA synthesis repair or loss of
control of proto-oncogene activity
 High intake reduces the risk of CRC
 1998 FDA required folate supplementation of flour, cereals,
and grain products
 Alcohol
 Increased risk for consumption o f 2 or more drinks a day
Environmental
 Smoking
 Two to three fold increase of adenoma risk in smokers
 Defined significant risk as smoking greater than 20 cigarettes
for 35-40 years
 Mechanism
Generates replication errors
 DNA mismatch repair genes
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Predisposing Medical Conditions
 Inflammatory Bowel Disease
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Ulcerative Colitis
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2% risk at 10 years/ 8% at 20 years/ 18% at 30 years
Crohn’s Disease
 Cholecystectomy
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Bile salt irritation
Increased risk for proximal small bowel and colon malignancy
 Ureterosigmoidostomy
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Ureterosigmoid anastomosis at risk
26 year latency period
About 25% will develop neoplasia
 Radiation
 Acromegaly
Genetic
 Hereditary Syndromes
 Familial Adenomatous Polyposis
 Hereditary Non-Polyposis Colorectal Cancer
 Others
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Peutz Jehger’s Syndrome
 Family History
 First degree relative with CRC or adenoma
Molecular Basis of CRC
ALTERATIONS IN REGULATORY MECHANISM
MUTATIONS
TRANSFORMATION
Alterations in Regulatory Mechanisms
 Six basic changes
1. Self sufficiency in growth signals
2. Insensitivity to anti-growth signals
3. Evading apoptosis
4. Limitless potential for cell replication
5. Sustained angiogenesis
6. Development of ability to invade and metastasize
Genetic Mutations
 Oncogenes
 K-ras
most frequently mutated gene in CRC
 Involved in transduction of exogenous growth signals
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 Tumor suppressor genes
 Inhibit cellular proliferation or promote apoptosis
 Both alleles must be inactivated: Two Hit Theory
 APC gene mutation
Adenoma to cancer pathway
 Found in 75% of sporadic cases of CRC
 Causes hyperproliferation
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Adenoma to Carcinoma Sequence
Normal
epithelium
Hyperproliferative
epithelium
APC
mutation
K-ras
mutation
Adenoma
DCC
Carcinoma
P53
mutations
Colon Cancer Screening
AVERAGE RISK
PERSONAL HISTORY OF ADENOMA OR CRC
FAMILY HISTORY OF ADENOMA OR CRC
HNPCC
FAP
IBD
Average Risk
 Who is average risk?
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No family or personal history of CRC
No symptoms to suggest CRC
No unexplained anemia
No IBD
 Recommendations: Begin at age 50
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FOBT annually
Flex sig every 5 years
FOBT and flex sig every 5 years
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Air contrast BE every 5-10 years
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15-25% with negative results harbor neoplasia in proximal colon
Detects 50-80% stage I and II adenocarcinoma
Colonoscopy every 10 years
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GOLD STANDARD
High Risk: Personal History Adenoma or CRC
 Surveillance Colonoscopy is Test of Choice*
 Prior adenoma
 > 3 adenomas or > 1 large adenoma or high risk lesion calls for
repeat within 6 to 12 months
 1-2 small adenomas- repeat in 3-5 years
 Prior CRC
 Post resection colonoscopy 1 year after surgery and every year
thereafter until colon is cleared
 Followed by colonoscopy every 3-5 years thereafter
Family History Adenoma or CRC
 For patients with first degree relatives diagnosed
with CRC:
 Screening colonoscopy at age 40, or 10 years before
the age of diagnosis of the affected relative
HNPCC
 Autosomal dominant inherited disorder
 Mutation in MMR genes (genes that code for proteins
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responsible for correcting errors during DNA replication)
Patients develop CRC between age 40 to 50
Most tumors are proximal to splenic flexure
Extra-colonic tumors are common
Amsterdam Criteria
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3 family members affected by CRC or HNPCC extra-colonic cancer
2 generations with one member being a first degree relative of the
other
1 having cancer diagnosis before age 50
HNPCC
 Screening colonoscopy
 Begins at age 20-25
 Repeat every 1-3 years
FAP
 Autosomal dominant
 Hundred and thousands of polyps
 Cancer before age 40
 Colonoscopy
 Puberty
 Repeat every 1-2 years
 Increased risk for neoplasia 7-8
IBD
years after diagnosis for pancolitis and 12-15 years after dx left
colitis
 Screening colonoscopy
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7-8 years after initial diagnosis and
every 1-2 years thereafter with multiple
biopsies to detect dysplasia
12-15 years for left sided colitis and
ever 1-2 years thereafter
Colonoscopy
Barium Enema
Pedunculated Polyp
 VA study
Flat Nonpolypoid Polyp
 Prevalence 9%
 Smaller more aggressive polyp
 Formerly a eastern polyp
 Best seen after training
 High definition
 Narrow band imaging
 Chromoendoscopy
Colon Cancer Evaluation and
Staging
CLINICAL PRESENTATION
STAGING AND PROGNOSTIC FACTORS
HISTOLOGIC FACTORS
SPREADING PATTERNS
Clinical Presentation
 Symptomatic patients
 Abdominal pain= MC
Vague and non-specific
 Poorly localized
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Changes in bowel habits
Depends on the side of the lesion
 Possibilities
 Pencil thin stool
 Mucus in BM
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Rectal bleeding
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17.5% patients had colorectal neoplasm in one series 570 patients
50 years or younger undergoing colonoscopy for bleeding
Occult blood in the stool
Preoperative Preparation
 Evaluate operative risks
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Nutrition
Co-morbidities (CAD, COPD, DM, Steroids)
 Localize and confirm tumor
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Review colonoscopy
Pathology
Radiography
 Stage
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CT CAP w/ oral and iv contrast
CEA
 Bowel Prep
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Controversial
No one likes operating in stool
Staging
 Outdated
 Dukes
A- Cancer limited to bowel wall
 B- Cancer extends to extracolonic tissue
 C- Cancer with regional lymph node metastasis
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 Current Staging System
 TNM
Staging: TNM
• Tumor
 T1- Into submucosa
 T2- Into muscularis propria
 T3- Through bowel wall
 T4- Adjacent structures
 Nodes
o N1- 1-3 nodes positive
o N2- 4 or more positive
 Metastasis
 M0- no metastasis
 M1- Metastasis
 Stage I
 Any T1 or T2, N0, M0
 Stage II
 Any T3 or T4, N0, M0
 Stage III
 A- T1 or 2, N1, M0
 B- T3 or 4, N1, M0
 C- Any T, N2, M0
 Stage IV
Histologic Factors
 Histologic Grade
 Well/ moderately/ poorly differentiated
 Mucin Production
 Signet-cell
 Low curative resection rate
 Mean survival 16 months
 Venous Invasion
 Perineural Invasion
 Lymph Node Involvement
 Most important prognostic indicator
 Need 13 or more for accurate staging
 CEA
 Correlates with metastatic disease
 > 15 mg/ml predicts increased risk of metastasis in otherwise curable
colon cancer
Spreading Patterns
Spreading Patterns
 Intramural Spread
 Rarely spreads this way
 Extent of average spread is 2cm
 Basis behind 5 cm margin
 Transmural Spread
 En-block resection indicated for
cure
 Margins
 5cm proximal and distal margin
 High ligation of primary feeding
vessel
 Radial Margins
 Becomes an issue in rectal cancer
Pelvic Structures
Spreading Patters
 Lymphatic
 MC mechanism for metastatic disease
 Causes metastatic liver disease
 T1- 9% risk of positive LN
 T2- 25% risk
 T3- 45% risk
 Hematogenous
 Bypass liver and goes to systemic circulation
 Explains lung mets in colon cancer
 Synchronous
 6% or less will have synchronous CRC
 Think HNPCC
 Give TAC
 Distant
 Liver
 Lung
Surgical Management
PREOPERATIVE PREPARATION
REVIEW OF SURGICAL OPTIONS
Surgical Options
 Right Colectomy
 Lesion located in cecum/ ascending colon
 Extended Right Colectomy
 Lesion located in the transverse colon (hepatic flexure to splenic flexure
 Left Colectomy
 Lesion in descending colon
 Sigmoid Colectomy
 Total Abdominal Colectomy Ileorectal Anastomosis versus
Total Proctocolectomy Ileal Pouch Anal Anastomosis
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HNPCC
Attenuated FAP/ FAP
Metachronous colon cancers
Distal obstruction with unknown proximal status