VALERIE P. BAUER, MDDIVISION OF COLON AND RECTAL SURGERY
ASSISTANT PROFESSORDEPARTMENT OF SURGERY
UTMB GALVESTONJUNE 8, 2011
Colon Neoplasia
COMMONINCREASING INCIDENCEDECREASING MORTALITY
Epidemiology
Epidemiology
Third most common diagnosed cancer and cause of cancer death annually
1 million people develop CRC annually150,000 cases will be diagnosed in USProbability of individual developing CRC in
US is %6 over a lifetimePopulation risk factors
Age Ethnicity Race Socioeconomic status
AGEDIETARY
ENVIRONMENTALPREDISPOSING MEDICAL CONDITIONS:
PRIOR HISTORY COLON CANCER OR POLYPSINFLAMMATORY
GENETIC
Etiology
Dietary Risk Factors for CRC
Saturated animal fatRed meat
High in iron- a pro-oxidant May increase free radicals that damage mucosa Charbroiled meat contains aromatic hydrocarbons
Increasing RM consumption by 3.5 oz/ day is associated with 12-17% 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 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
Calcium Binds and precipitates bile salts Beneficial in two randomized double blind placebo controlled
trials 1200mg/ day for 4 years 2000mg/ day 3 years
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
Predisposing Medical Conditions
Inflammatory Bowel Disease Ulcerative Colitis
2% risk at 10 years/ 8% at 20 years/ 18% at 30 years Crohn’s Disease
Cholecystectomy Bile salt irritation Increased risk for proximal small bowel and colon
malignancyUreterosigmoidostomy
Ureterosigmoid anastomosis at risk 26 year latency period About 25% will develop neoplasia
RadiationAcromegaly
Genetic
Hereditary Syndromes Familial Adenomatous Polyposis Hereditary Non-Polyposis Colorectal Cancer Others
Peutz Jehger’s Syndrome
Family History First degree relative with CRC or adenoma
ALTERATIONS IN REGULATORY MECHANISMMUTATIONS
TRANSFORMATION
Molecular Basis of CRC
Alterations in Regulatory Mechanisms
Six basic changes1. Self sufficiency in growth signals2. Insensitivity to anti-growth signals3. Evading apoptosis4. Limitless potential for cell replication5. Sustained angiogenesis6. 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
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
Adenoma to Carcinoma Sequence
Normal epithelium
Hyperproliferativeepithelium
Adenoma Carcinoma
APCmutation
K-rasmutation
DCC P53mutations
AVERAGE RISKPERSONAL HISTORY OF ADENOMA OR CRC
FAMILY HISTORY OF ADENOMA OR CRCHNPCC
FAPIBD
Colon Cancer Screening
Average Risk
Who is average risk? No family or personal history of CRC No symptoms to suggest CRC No unexplained anemia No IBD
Recommendations: Begin at age 50 FOBT annually Flex sig every 5 years FOBT and flex sig every 5 years
15-25% with negative results harbor neoplasia in proximal colon
Air contrast BE every 5-10 years Detects 50-80% stage I and II adenocarcinoma
Colonoscopy every 10 years 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 yearsPrior 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 disorderMutation in MMR genes (genes that code for proteins
responsible for correcting errors during DNA replication)
Patients develop CRC between age 40 to 50 Most tumors are proximal to splenic flexureExtra-colonic tumors are commonAmsterdam Criteria
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 dominantHundred and thousands of polypsCancer before age 40Colonoscopy
Puberty Repeat every 1-2 years
IBDIncreased risk for neoplasia
7-8 years after diagnosis for pan-colitis and 12-15 years after dx left colitis
Screening colonoscopy 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
Barium Enema Pedunculated Polyp
Colonoscopy
Flat Non-polypoid Polyp
VA studyPrevalence 9%Smaller more aggressive
polypFormerly a eastern polypBest seen after trainingHigh definitionNarrow band imagingChromoendoscopy
CLINICAL PRESENTATIONSTAGING AND PROGNOSTIC FACTORS
HISTOLOGIC FACTORSSPREADING PATTERNS
Colon Cancer Evaluation and Staging
Clinical Presentation
Symptomatic patients Abdominal pain= MC
Vague and non-specific Poorly localized
Changes in bowel habits Depends on the side of the lesion Possibilities
Pencil thin stool Mucus in BM
Rectal bleeding 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 Nutrition Co-morbidities (CAD, COPD, DM, Steroids)
Localize and confirm tumor Review colonoscopy Pathology Radiography
Stage CT CAP w/ oral and iv contrast CEA
Bowel Prep 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
Current Staging System TNM
Staging: TNM
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
• Tumor T1- Into submucosa T2- Into muscularis propria T3- Through bowel wall T4- Adjacent structures
Nodeso N1- 1-3 nodes positiveo N2- 4 or more positive
Metastasis M0- no metastasis M1- Metastasis
Histologic Factors
Histologic Grade Well/ moderately/ poorly differentiated
Mucin ProductionSignet-cell
Low curative resection rate Mean survival 16 months
Venous InvasionPerineural InvasionLymph 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 Pelvic Structures
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
Spreading Patterns
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
PREOPERATIVE PREPARATIONREVIEW OF SURGICAL OPTIONS
Surgical Management
Surgical Options
Right Colectomy Lesion located in cecum/ ascending colon
Extended Right Colectomy Lesion located in the transverse colon (hepatic flexure to splenic
flexureLeft Colectomy
Lesion in descending colonSigmoid ColectomyTotal Abdominal Colectomy Ileorectal Anastomosis versus
Total Proctocolectomy Ileal Pouch Anal Anastomosis HNPCC Attenuated FAP/ FAP Metachronous colon cancers Distal obstruction with unknown proximal status
Top Related