Roys Pangayoman, dr.

, SpB

Colorectal cancer is the most common cancer of the GIT. In : 2nd after breast cancer, in: 3rd after lung and prostate carcinoma.
(2001: Cancer: Principles and Practice of Oncology 6)

10% occur in patients with genetic predisposition (Lynch syndrome I / II or HNPCC* ; FAP) Literature:

Mostly >50 y.o. (Kodner,I.J.; Fry,R.D., 1994)

155.000 new cases each year (40% will die of the disease)

USA, 1992

*HNPCC = Hereditary NonPolyposis Colon Carcinoma

Predisposition to Mutagen Effects

Protection from the effects of mutagen-induced DNA

damage is achieved by a range of detoxification enzymes. Detoxification enzymes: glutathione S-transferase (GSH transferase), DT-diaphorase, and Nacetyltransferase. Reduction in these enzymes enhances the risk for colorectal cancer.

Fecal Mutagens
Mutagens: fecapentaenes, 3-ketosteroids, and

heterocyclic amines in the stool may be produced by the interaction of digestion and food products (red meat).

 Environmental
Diet: Fats considered toxic, while monosaturated fatty acids (omega-3 & omega-6) less carcinogenic Meat Intake high correlation of meat intake and mortality from colorectal cancer Bile acids (chenodeoxycholic acid) of fat can induce intestinal mucosal hyperproliferation, which increase neoplasia risk. Daily alcohol intake has been associated with a twofold increase in colon carcinoma.

Others:
Infection: amoebiasis (?) Fecal pH: higher rates of colon carcinoma are

found in subjects with a higher stool pH.

 Clinical:
Age: especially those >50 years

old. The peak onset of colorectal cancer in the United States is at age 65 years.

(however in Indonesia, young adults and children are included)

 Genetic

Predisposition:

Hereditary Polyposis Syndrome: Familial Adenomatous Polyposis (FAP) Gardners syndrome (osteoma, skin tumor, intestine polyposis) Turcots syndrome (colonic tumors and brain tumors, is also linked to medulloblastoma) Hereditary Nonpolyposis Syndrome

(HNPCC):

Lynch I (limited to the colorectum) Lynch II (coexist with extracolonic tumors, typically endometrial cancer)

 Acquired Somatic Syndrome Peutz-Touraine-Jeghers Syndrome Juvenile Polyposis Family History of Colon Carcinoma or

Polyps

 Premalignant

conditions:

Inflammatory Bowel Disease Ulcerative colitis Incidence of neoplasia in pancolitis patients is 10% by 20 years duration of disease More difficult to find in early stage 35% are Dukes C and D lesions Granulomatous colitis: Crohns disease
Overall incidence is 7% over 20 years duration of Crohns disease

 Non-Cancer

Surgery:

Some studies suggest that

cholecystectomy increases the incidence of colorectal cancer. The relationship between cholecystectomy and colorectal carcinoma is controversial.

 Dietary

Factors:

Fiber: Dietary fiber lower the incidence of cancer in patients who have a high-fat diet Vitamins & Minerals: Calcium can alter colonic mucosal proliferation by binding fatty acids and bile acids in the stool, resulting in insoluble complexes that are less likely to affect the mucosa reduce risk for colorectal Ca. Folate, Vitamin C, Vitamin D, Vitamin E all reduce risk for colorectal Ca.

 Dietary fat: Fish oils may have protective effects. Elevated levels of serum triglycerides have been associated with a higher risk of adenomatous polyps. Interestingly, lower cholesterol levels have been demonstrated in patients in whom colorectal cancer is diagnosed.

 Hormone

Replacement in Women:

Current use of postmenopausal hormones was

Energy

Intake, Physical Activity, and Obesity:

associated with decreased risk of colorectal cancer.

Restricted energy intake has reduced the

development of colonic tumors, while reduced physical activity increases the risk. Excessive weight and abdominal obesity were found to be risk indicators in men and women.

 NSAIDs:
colon tumors contain increased amounts of

prostaglandin E(2), and this compound is thought to participate in colon cancer carcinogenesis. COX-2 appears to be responsible for increased prostaglandin E(2 )in response to growth factors in human and animal colonic tumors. COX-2 inhibition, therefore, may play a role in colon cancer prevention. COX-2 inhibitor: aspirin, sulindac, nimesulide, etc.

 Focuses

on the identification of high-risk populations and interventions that can prevent the development of colorectal carcinoma. Involves: screening for adenomas, treatment of adenomatous polyps by endoscopic polypectomy, or excision of the large bowel in FAP.

Normal epithelium Hyperproliferative epithelium

Gene alterations

5q mutation or loss DNA hypomethylation Early adenoma 12p mutation of K-RAS Intermediate adenoma 18q loss (DCC) Late adenoma 17p loss (p53) Carcinoma Other alterations Metastasis

 Early signs/ symptoms are NOT spesific By pathogenesis of the carcinoma:

Subacute presentation Diarrhea paradoxic Dark / starry stools Iron-deficiency anemia (occult bleeding) Lower abdominal pain cramping Weight loss, fever

 Acute Presentation Mainly obstruction or perforation symptoms Inability to pass flatus or feces Cramping abdominal pain Abdominal distention If obstruction is not relieved ischemia necrosis severe abdominal pain (perforation and sepsis might occur)

Right colon:
Anemia, fatigue Occult blood in feces Dyspepsia Persistent right

Left Colon:
Alteration in bowel habit Bloody stools Intestinal obstruction Diarrhea and obstipation (diarrhea paradoxa)
Ring-like (Karzinomstenose) Sturdy (hard lesion)

abdominal discomfort Abdominal mass Diarrhea: bloody and mucus (DurchfallKarzinom)

Fungoid / Popypoid (exophytic) More fragile

Carcinoma recti:

Rectal bleeding Sensation of incomplete bowel discharge

Touch: mass (+)

Digital rectal examination (rectal touch)

Can reach app. 8 cm above the dentate line May detect almost

50% of colorectal cancer Flexible sigmoidoscopy

May identify 50% colorectal cancer

Contrast studies Colonoscopy

preparation
Double contrast barium enema 90% sensitive The most accurate method Requires patients compliance, bowel

 Imaging: Chest X-ray & Liver function tests: To rule out pulmonary and liver metastasis May suggest the need for CT-scanning CEA (Carcinoembryonic antigen):
Important in the evaluation of colorectal cancer Nonspesific Have high correlation with tumor metastasis if > 5 ng/ml !!! CT: 95% sensitive, can identify metastasis

 Recommendations

of the American Cancer Society for colorectal cancer:

A yearly digital exam is recommended

for ALL patients >40 y.o. Patients >50 y.o. : DRE (Digital Rectal Examination) with occult blood testing and should have flexible sigmoidoscopy every 3-5 years.

>90% are adenocarcinomas 4 morphologic variants:

Ulcerative: Descending & sigmoid colon Exophytic (polypoid/ fungating): Ascending colon (caecum) Annular (scirrhous): Descending colon Other: mucoid (colloid); signet-ring cell; adenosquamous; undifferentiated

Modified Astler-Coller classification of the DUKES staging system:

Stage A B1 B2 C1 C2 D Description
Lesion not penetrating submucosa Lesion up to, but not through, serosa Lesion through serosa, with involvement of adjacent organs Lesion up to, but not through, serosa; regional lymph node metastasis Lesion through serosa, with involvement of adjacent organs; regional lymph node metastasis Distant metastatic disease
Cancer: Principles & Practice of Oncology 6th Ed., 2001

 Futher

modified Astler-Coller by Gunderson and Sosin in DUKES system, subdividing the patients based on the presence of microscopic (B2m or C2m) and gross penetration (B2m + g, and C2m + g) through the bowel wall.
SOURCE: Cancer: Principles & Practice of Oncology 6th Ed., 2001

Primary tumor (T):

T1 T2 T3 T4

Invades Invades Invades Invades

into

N0 N1 N2 N3

submucosa muscularis propria subserosa but not through serosa through serosa into free peritoneal cavity contiguous organ

Regional lymph nodes (N):

No lymph node metastases Lymph node metastases in 1-3 nodes Lymph node metastases in 4 or more nodes Lymph node metastases in central nodes No distant metastases Distant metastases present

Distant metastases (M):

M0 M1

Stage 0 I II III IV

Tumor (T) Tis T1 T2 T3 T4 Any T Any T Any T

Lymph Nodes (N) N0 N0 N0 N0 N0 N1 N2 Any N

Metastasis (M1) M0 M0 M0 M0 M0 M0 M0 M1

Cancer: Principles & Practice of Oncology 6th Ed., 2001

 Carcinoma

of the colon: through the venous and lymphatic drainage, parallels with arterial supply for the colon directly to the LIVER via portal venous system Carcinoma of the rectum:
Upper part (8-16 cm from anus) drains into

the portal system liver Lower part (middle third and distal third) middle and inferior hemorrhoidal veins (rectal veins) vena cava inferior directly to the heart and lung

 Obstruction Perforation:

(ileus):

ILEUS

In good-risk patient, treated by immediate

resection

Aggressive approach to perforated cancer

Direct

of the colon is advisable, but anastomosis usually is delayed

extension:

When spread to adjacent organs (small

intestine, spleen, uterus, bladder), they should be resected en-block with the colon

NOTE: Intestinal tumors in the adults may cause ileus (intestinal obstruction) due to invagination (intussuseption) Case 1996-2000 RSI of Adults intussuseption (invagination): 7 patients, male: 2, female: 5 Age: 20-30 (43%), > 50 (67%) Chief complaint: abdominal pain (66%), vomitus (22%) Pure invagination (48%); Tumor as the cause (52%) Tumor: malignant lymphoma (33%), colon carcinoma (33%)

 Operative

surgery (laparotomy or laparoscopic resection) is the primary option For colon: 5-YSR:
Right hemicolectomy
T1-T2 in nodenegative disease:90% Right radical hemicolectomy T3: 80% Transverse colectomy Node (+): 27-69% UnresectableLeft hemicolectomy Low anterior resection metastatic disease: 5%

Subtotal colectomy

 For

Node (-): 75-90% Node (+): 30% Approaches: Recurrence rate: Abdominoperineal resection 10-50% Low anterior resection Coloanal anastomosis Transanal approaches Transsacral approaches (York-Mason, Kraske)

rectum:

5-YSR:

Procedures: Sphincter-Preservation procedure Colonic J Pouch

End of session