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