PROGNOSIS

Prognosis depends on stage

• If patient has stage I (T1-2N0) colon cancer 5 year survival is 93 percent [59]
• If patient has stage IIA (T3N0) or stage IIB (T4N0), 5 yr survival is 85 percent and 72 percent respectively [59]
• If patient has stage IIIA (T1-2 N1), IIIB (T3-4 N1) or IIIC (N2), 5 yr survival is 83, 64 and 44 percent respectively [59]
• If patient has stage IV ca colon, 5 yr survival is 8% [59]
• If patient has ca rectum and is in stage IIIA (T1-2, N1), IIIB (T3-4, N1) or IIIC, 5 yr survival is 55.1, 35.3 and 24.5 percent respectively [60]


COUNCELLING


The things you can do to lower your risk include the following:
• Quit smoking. Smoking cigarettes has been clearly linked with higher risk of colon cancer (as well as many other conditions).
• Take an aspirin every day. Because of potential side effects, this is not recommended for everyone. Talk to your health care provider first.
• Take a safe dose of folic acid (for example, 1 mg) every day.
• Engage in physical activity every day.
• Eat a variety of fruits and vegetables every day.
• Avoid red meats and saturated fats
• Increase fiber in your diet
• People who have one first-degree relative (parent, brother, sister, or child) who has experienced colorectal cancer or adenomatous polyps at a young age (before the age of 60 years), or two first-degree relatives diagnosed at any age, should begin screening earlier, typically at age 40, or 10 years younger than the earliest diagnosis in their family, whichever comes first, and screening should be repeated every 5 years
• People who have one first-degree relative (parent, brother, sister, or child) who has experienced colorectal cancer or adenomatous polyps at age 60 or later should begin screening at age 40, and screening should be repeated as for average risk people. People with a second-degree relative (grandparent, aunt, or uncle) or third-degree relative (great-grandparent or cousin) with colorectal cancer may be screened as average risk people.
• Every patient after 40 years of age should undergo screening for colon cancer


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SURVEILLANCE
• Coordinate physician visits every 3 to 6 months for the first 3 years, every 6 months during years 4 and 5, and subsequently at the discretion of the physician after treatment of colorectal carcinoma [57].
• Physician visits should focus on the initial risk assessment, followed by the implementation of a surveillance strategy and periodic counseling based on estimated risk and feasibility of surgical interventions like hepatic resection [57].
• For patients at lower risk of recurrence (stages I and Ia) or those with co morbidities impairing future surgery, only visits yearly or when symptoms occur are recommended [58]
• For patients at lower risk of recurrence (stages I and Ia) should have a colonoscopy before or within 6 months of initial surgery, repeated yearly if villous or tubular adenomas >1 cm are found; otherwise, repeat every 3 to 5 years [58]
• Postoperative serum CEA, CEA every 3-6 mo for 2 y, then every 6 mo for a total of 5 y for T2 or greater lesions, if the patient is a candidate for surgery or systemic therapy [56]
• Since fluorouracil-based therapy may falsely elevate CEA values, waiting until adjuvant treatment is finished to initiate surveillance is advised [57].
• If serial CEA level is increasing advise physical examination, colonoscopy and CT chest, abdomen and pelvis [56]
• If findings are negative consider PET scan and reevaluate chest/ abdominal/pelvic CT in 3 months [56]
• If metachronous tumor is documented treat accordingly [56]
• Routine blood tests (i.e., complete blood counts or liver function tests) are not recommended for surveillance [57].
• Periodic fecal occult blood testing or X Ray chest is not recommended [57].
• Patients who are at higher risk of recurrence, and who could be candidates for curative-intent surgery, should undergo annual CT of the chest and abdomen for 3 years after primary therapy for colon and rectal cancer [57].
• A pelvic CT scan should be considered for rectal cancer surveillance, especially for patients who have not been treated with radiotherapy
• All patients with colon and rectal cancer should have a colonoscopy for the pre- or perioperative documentation of a cancer- and polyp-free colon. Following the surgical treatment of colorectal cancer, a colonoscopy in 1 y: If abnormal, repeat in 1 y. If negative for polyps, repeat in 3 y, then every 5 y. If no preoperative colonoscopy due to obstructing lesion, colonoscopy in 3-6 months should be done [57]
• For patients of rectal cancer who have not received pelvic radiation, flexible sigmoidoscopy of the rectum every 6 months for 5 years is recommended [57].

• Acutely bleeding colon cancers that require emergent resection should be removed following the same principles as in elective resection
Staging of Colon Cancer [2].
• Colon cancers should be staged using the Primary Tumor, Regional Lymph Nodes, Distant Metastasis (TNM) staging system
• To be properly evaluated, one should strive to have a minimum of 15 lymph nodes examined microscopically.

Adjuvant Therapy [2].
• Postoperative adjuvant systemic chemotherapy has a proven benefit in Stage III colon cancer and may be beneficial in certain high risk Stage II patients
• Patients with Stage III colon cancer are recognized to be at high risk for recurrence, and administration of 5-fluorouracil (5-FU)/leucovorin for six months postoperatively has proven benefit in decreasing recurrence and improving survival.
• Standard therapy for metastatic colon cancer is CPT11 (irinotecan) plus 5-FU/leucovorin, also known as the Saltz regimen. In 2005, the standard therapy for metastatic colorectal cancer is IFL plus bevacizumab (irinotecan, 5-FU, leucovorin, Avastin).
o Each of the agents in the Saltz regimen is administered by IV injection weekly for 4 weeks every 6 weeks.
o Diarrhea is the most commonly encountered adverse effect with this regimen. Other adverse effects include mucositis, neutropenia, hair loss, and skin hypersensitivity reactions. The combination of 5-FU/leucovorin/CPT11 has the potential for severe toxicity, mainly diarrhea leading to dehydration and vascular collapse, in some patients. Many clinicians start therapy with an approximately 25% decrease in doses of CPT11 (100 mg/m2 rather than 125 mg/m2) and 5-FU (400 mg/m2 rather than 500 mg/m2) and escalate to full doses only if the initial cycle of treatment is well tolerated.
• The addition of levamisole does not seem to add any benefit. The addition of interferon alpha-2a does not improve disease-free survival or overall survival, but does increase toxicity.
• Patients with Stage II colon cancer who are considered at higher risk for recurrence include those with one or more of the following characteristics: tumor perforation, adherence, or invasion of adjacent organs; nondiploidy by flow cytometry; poorly differentiated tumor; or venous, lymphatic, and perineural invasion. It may be advantageous for these patients to receive adjuvant chemotherapy. Ideally, this should be performed within the confines of a clinical trial.
• The value of immunotherapy for colon cancer is undetermined. Its use is recommended within the setting of a clinical trial
• Intraperitoneal and intraportal infusions of chemotherapy are recommended only in the confines of a clinical trial
• Intrahepatic chemotherapy for colon cancer with liver metastasis is intra-arterial floxuridine (FUDR) [55].
o Following resection of the primary colon cancer and lymph nodes, 2 options for chemotherapy exist: systemic chemotherapy with a standard regimen such as 5-FU/leucovorin/CPT11 or intrahepatic (intraarterial) chemotherapy with FUDR.
o The second option is worth considering for patients with large or multiple liver lesions because this route results in delivery of a higher dose of chemotherapy to the liver metastases. The underlying principle is that liver metastases derive their blood supply primarily through the hepatic arterial circulation, whereas normal liver derives most of its blood supply through the portal vein.
o The major adverse effect of intra-arterial FUDR is sclerosing cholangitis, which may be quite severe and may necessitate discontinuation of therapy. [2].
• Palliative chemotherapy for patients with metastatic colorectal cancer aims to improve survival and quality of life. Resection of metastatic disease (hepatic or pulmonary metastases) can lead to 5-year survival rates of 35-58%. About 15% of patients with liver metastases initially judged to be unresectable will become resectable after systemic chemotherapy, with excellent long-term survival [22]
• Radiation is rarely used in the treatment of colon cancer. Radiation's potential for injury to the abdominal viscera limits its usefulness
• Patients with rectal cancer must be referred for radiation oncology consultation. Radiation has been demonstrated to reduce the risk of local recurrence of rectal cancer following surgical resection. Thus, in the adjuvant setting, the therapy for rectal cancer includes combination of radiation and chemotherapy. This is a basic difference between the therapy of colon cancer and rectal cancer [2].

SURVEILLANCE
• Coordinate physician visits every 3 to 6 months for the first 3 years, every 6 months during years 4 and 5, and subsequently at the discretion of the physician after treatment of colorectal carcinoma [57].
• Physician visits should focus on the initial risk assessment, followed by the implementation of a surveillance strategy and periodic counseling based on estimated risk and feasibility of surgical interventions like hepatic resection [57].
• For patients at lower risk of recurrence (stages I and Ia) or those with co morbidities impairing future surgery, only visits yearly or when symptoms occur are recommended [58]
• For patients at lower risk of recurrence (stages I and Ia) should have a colonoscopy before or within 6 months of initial surgery, repeated yearly if villous or tubular adenomas >1 cm are found; otherwise, repeat every 3 to 5 years [58]
• Postoperative serum CEA, CEA every 3-6 mo for 2 y, then every 6 mo for a total of 5 y for T2 or greater lesions, if the patient is a candidate for surgery or systemic therapy [56]
• Since fluorouracil-based therapy may falsely elevate CEA values, waiting until adjuvant treatment is finished to initiate surveillance is advised [57].
• If serial CEA level is increasing advise physical examination, colonoscopy and CT chest, abdomen and pelvis [56]
• If findings are negative consider PET scan and reevaluate chest/ abdominal/pelvic CT in 3 months [56]
• If metachronous tumor is documented treat accordingly [56]
• Routine blood tests (i.e., complete blood counts or liver function tests) are not recommended for surveillance [57].
• Periodic fecal occult blood testing or X Ray chest is not recommended [57].
• Patients who are at higher risk of recurrence, and who could be candidates for curative-intent surgery, should undergo annual CT of the chest and abdomen for 3 years after primary therapy for colon and rectal cancer [57].
• A pelvic CT scan should be considered for rectal cancer surveillance, especially for patients who have not been treated with radiotherapy
• All patients with colon and rectal cancer should have a colonoscopy for the pre- or perioperative documentation of a cancer- and polyp-free colon. Following the surgical treatment of colorectal cancer, a colonoscopy in 1 y: If abnormal, repeat in 1 y. If negative for polyps, repeat in 3 y, then every 5 y. If no preoperative colonoscopy due to obstructing lesion, colonoscopy in 3-6 months should be done [57]
• For patients of rectal cancer who have not received pelvic radiation, flexible sigmoidoscopy of the rectum every 6 months for 5 years is recommended [57].

• The sensitivity of CT scans in detecting metastatic lymphadenopathy ranges from 19 to 67 percent. Many series have reported the utility of CT in detection of liver metastases and cite sensitivities and specificities between 90 and 95 percent for lesions > 1 cm.
• There is a trend toward the routine use of preoperative evaluation of patients with CT scans, especially in cancer centers in which synchronous resections of the primary and metastatic cancers are increasing
• It is common practice among surgeons to obtain a chest x-ray preoperatively to evaluate the lungs for evidence of metastatic disease. Although the yield for metastatic disease is low, the cost is small, and the utility of the examination is part of an overall preoperative assessment
Preparation for Operation[2].
• All patients who are to undergo surgery for colon cancer need to be clearly informed of the reasons for and the extent of the proposed resection, the likely outcome of the surgery, the pertinent complications and their likelihood of occurring, expected length of hospitalization and recovery, alternatives to the proposed surgery, and prognosis
• Mechanical bowel preparation is nearly universal for elective surgery but outpatient bowel preparation can be safe and cost effective.
• Prophylactic antibiotics are recommended for patients undergoing colon resection
• Preoperative blood transfusions may be required for patients undergoing resection for colorectal cancer. The need for transfusion is primarily based on the starting hemoglobin, the patient's physiologic status, and extent of intraoperative blood loss.
• All patients undergoing surgery for colon cancer should receive prophylaxis against thromboembolic disease.


Operative Issues [2].
• The extent of resection of the colon should correspond to the lymphovascular drainage of the site of the colon cancer
• Tumors located in border zones should be resected with the neighboring lymphatic regions to encompass both possible directions of spread
• Laparoscopic-assisted colectomy may be considered based upon the following criteria:
• Surgeon with experience performing laparoscopically-assisted colorectal operations.
• No disease in rectum or prohibitive abdominal adhesions.
• No advanced local or metastatic disease.
• Not indicated for acute bowel obstruction or perforation from cancer.
• Thorough abdominal exploration is required
• Consider preoperative marking of small lesions.

• Synchronous colon cancers can be treated by two separate resections or subtotal colectomy
• Fifteen percent of patients with colon cancer will have tumors adherent to adjacent organs. They should be resected en bloc
• Between 10 and 20 percent of patients will have liver metastases at the time of their colon resection.
• Surgical excision or ablation of these tumors, when amenable, remains the only means of obtaining long-term survival in this group of patients. It is generally believed that such anatomic resections are best performed at a later date after recovery from the initial colonic resection.
• However, if at the time of the primary colon resection the patient is found to have limited metastatic disease in the liver, which is amenable to sub segmental resection or metastasectomy, it may be preferable to proceed with this additional procedure at the time of colectomy.
• Bilateral oophorectomy is advised when one or both ovaries are grossly abnormal or involved with contiguous extension of the colon cancer. However, prophylactic oophorectomy is not recommended
• Patients with an obstructing right or transverse colon cancer should undergo a right or extended right colectomy. A primary ileocolic anastomosis can be performed in the appropriate clinical setting
• The site of a colonic perforation caused by colon cancer should be resected, if at all possible

PREVENTION:

• If ca colon has to be prevented diets rich in fibers and vitamins and low in saturated fats should be advised. Screening for individuals at risk should be done at regular screening intervals. Drugs offering chemoprevention can betried in high risk patients
• Intake of a diet high in fruits and vegetables is protective from colorectal cancer.
• Diet low in red meat, animal fat and/or cholesterol may also be protective.
• If in populations with low average intake of dietary fiber, an approximate doubling of total fiber intake from foods is done, this could reduce the risk of colorectal cancer by 40 percent.
• Other possible protective factors, decreasing the incidence of CRC include folic acid, Vitamin B6, calcium and magnesium
• Postmenopausal hormone use may reduce the risk of colorectal cancer [53].
• If patient is at risk of ca colon, protective effect of aspirin and other nonsteroidal anti-inflammatory drugs on the development of colon cancer is described in various studies. How long-term aspirin or NSAID therapy might protect against colon cancer is not well understood [53]
• HMG-CoA reductase inhibitors (statins) may have a protective effect against several cancers, including colon cancer, although the data are conflicting [54]

TREATMENT
Surgery is the only curative modality for localized colon cancer. In addition, it is often required for diagnosis, staging or palliation of tumor-related obstruction or bleeding [2].
• Once a colon cancer has been detected, prompt preoperative evaluation and treatment is warranted [2].
• A crucial part of this evaluation is to ensure that the patient's entire colon and rectum have been assessed with colonoscopy for the presence of synchronous neoplasms.
• In cases in which the colon cancer prevents the proximal bowel from being examined, colonoscopy should be performed within a few months of the definitive surgery.
• Most patients diagnosed with colon cancer will require an operation.
• Depending on the patient's age and health status, a variety of laboratory, radiologic, and cardiorespiratory tests may be appropriate to assess the patient's operative risk
Preoperative Assessment [2].
• CEA is known to be elevated in a variety of conditions, including colorectal cancer, proximal gastrointestinal cancers, lung and breast cancers, benign inflammatory conditions of the gastrointestinal tract, and smoking. It has never been useful as a screening tool but has proven useful in individuals diagnosed with colorectal cancer.
• Drawing a CEA level has been recommended before and after resection of colorectal cancer [2].
• Postoperative return to normal of an elevated preoperative CEA is associated with complete tumor resection, whereas persistently elevated values indicate the presence of visible or occult residual disease. The interval recommended most commonly is every three months for the first two years. This allows enough time for CEA to return to baseline.
• Elevated preoperative CEA levels have been found to be an independent prognosticator of poor outcome.
• An elevated CEA is associated with future metastases in 37 percent of patients at five years vs. 7.5 percent of patients with normal CEA levels.
• If CEA level is >20 ng/ml before therapy consider a cancer which has already metastasized [62]
• If patient with ca colon has high preoperative carcinoembryonic antigen levels above 15 ng/ml, select patient for adjuvent therapy [62]
• CEA is positive in about 63% of patients having a colorectal carcinoma; about 20% of patient with Dukes A, 28% with Dukes B, 68% with Dukes C.
• In individuals in whom there is a suspicion of invasion of an adjacent organ (because of the presence of a palpable mass, unusual abdominal pain or other symptoms, or unexplained chemical abnormalities), a CT scan may be useful for preoperative planning [2].

PREVENTION:

PREVENTION: If patient is diagnosed to have ca colon determine the local and distant extent of disease spread in order to provide a framework for discussing therapy and prognosis by examining the biopsy specimen, having abdominopelvic ultrasonography/ CT for disease extent and X Ray chest for secondaries:
American Joint Committee on Cancer (AJCC) TNM Staging [56]
System for Colorectal Cancer
Primary Tumor (T)
Regional Lymph Nodes (N)
Distant Metastasis (M)
Stage Grouping
TX Primary tumor cannot be assessed
T0 No evidence of primary tumor
Tis Carcinoma : intraepithelial or invasion of lamina propria
T1 Tumor invades submucosa
T2 Tumor invades muscularis propria
T3 Tumor invades through the muscularis propria into the subserosa,
or into non-peritonealized pericolic or perirectal tissues
T4 Tumor directly invades other organs or structures, and/or perforates visceral peritoneum
NX Regional lymph nodes cannot be assessed
N0 No regional lymph node metastasis
N1 Metastasis in 1 to 3 regional lymph nodes
N2 Metastasis in 4 or more regional lymph nodes
MX Distant metastasis cannot be assessed
M0 No distant metastasis
M1 Distant metastasis


STAGE GROUPING [56]
Stage T N M Dukes MAC
0 Tis N0 M0 - -
I T1 N0 M0 A A
T2 N0 M0 A B1
IIA T3 N0 M0 B B2
IIB T4 N0 M0 B B3
IIIA T1-T2 N1 M0 C C1
IIIB T3-T4 N1 M0 C C2/C3
IIIC Any T N2 M0 C C1/C2/C3
IV Any T Any N M1 - D

• If the cancer is localized to the mucosa and submucosa, patient is said to have Dukes' A or TNM stage I [35]
• If the cancer is extending into or through the muscle layer without lymph node involvement patient is said to be in Dukes' B or TNM stage II [35]
• If there is lymph node involvement patient is said to be in Dukes' C or TNM stage III [35]
• If patient has distant metastases patient is said to be in Dukes' D or TNM stage IV [35]

SCREENING

• If person is 50 - 80 years of age having no personal or family history of colorectal carcinoma (Not having the following: A first degree relative or two second degree relatives with colorectal cancer, or clustering of HNPCC related cancers in the family) or no family history of adenomatous polyps before age of 60 yrs and no history of inflammatory bowel disease, advise cancer surveillance by either flexible sigmoidoscopy every 5 years, annual fecal occult blood test (FOBT), combination of flexible sigmoidoscopy or colonoscopy every 5 years and annual FOBT or total colon evaluation [32, 48]
• If patient is African American 45 to 80 years old having no personal or family history of colorectal carcinoma or no family history of adenomatous polyps before age of 60 yrs, advise cancer survillance by either flexible sigmoidoscopy every 5 years, annual fecal occult blood test (FOBT), combination of flexible sigmoidoscopy or colonoscopy every 5 years and annual FOBT or total colon evaluation [32]
• If colonoscopy is done (which is preferable if available) and is negative having no mass or polyps, repeat colonoscopy after 10 years. [48]
• If colonoscopy shows polyps recommend colonoscopic removal and histopathology of the specimen
• If polyp is hyperplastic advise routine colonoscopy after every 10 years. [48]
• If patient has polyp (adenoma with villous component, or any adenomatous polyp greater than 10 mm) or prior colorectal cancer advise colonoscopic surveillance at a 3- to 5-year interval [32]
• If patient has an abnormal sigmoidoscopy with significant pathology (single adenoma >1.0 cm, adenomas with tubulovillous or villous histology, or multiple adenomas) advise colonoscopy [37]
• If patient has an abnormal sigmoidoscopy with adenomas 0.6 to 1.0 cm, and for those with multiple adenomas advise colonoscopy
• For those with single tubular adenomas <0.6 cm, we advise discussing the marginal benefit of further investigation and seeking the patient's preference whether to proceed with colonoscopy.
• If fecal occult blood is advised to the patient, ask the patient to take the diet having no red meat or turnip/horseradishes (to prevent false-positive peroxidase reactions); no gastric irritant drugs (to prevent false-positive reactions from gastritis); no vitamin C (to prevent a false-negative chemical reaction); and high-fiber foods (to increase stool transit time) [36].
• If any sample of FOBT is positive proceed as follows [48]
Any positive test requires evaluation
3 successive stool specimens should be examined
Repeat test after prescribed diet
Sample not digital rectal examination
Guaiac-based nonrehydrated test should be performed
Immunochemical techniques are under investigation
Test should be coordinated by health care provider
Annual FOBT need not be performed if screening colonoscopy or doublecontrast enema is used as a screening measure in an average-risk patient

.
• If FOBT positive and colonoscopy negative, proceed with additional workup
• If patient has long standing inflammatory bowel disease involving the colon advise colonoscopic surveillance at a 1 to 2-year interval starting at 8 - 10 years from disease onset [32, 48]
• When clinically quiescent, 4 quadrant biopsies every 10 cm with > 30 total samples using large cup forceps (preferred). Additional extensive sampling of strictures and masses is also advised.
• Endoscopic polypectomy when appropriate with biopsies of surrounding mucosa for the assessment of dysplasia [48]
• The finding of definite dysplasia (of any grade) should be confirmed by an expert pathologist and is an indication for colectomy [38]
• Patients whose biopsies are indefinite for low grade dysplasia after review by an expert pathologist should undergo repeat surveillance colonoscopy at a shorter interval.

• If patient has High-grade dysplasia/intraepithelial neoplasia or Multifocal low-grade dysplasia/intraepithelial neoplasia, prophylactic proctocolectomy with ileoanal pouch should be considered [48]

• If patient has a family history of colorectal cancer they can be familial adenomatous polyposis, attenuated familial adenomatous polposis or othe varients and heridiatry non polyposis colorectal carcinoma.
• If patient has a family history of colorectal cancer involving one first order relative diagnosed before age 60, two first order relatives diagnosed at any age or a single first order relative diagnosed after age 60 advise colonoscopic surveillance at a 1- to 5-year interval begin at age 40 or 10 years before the index carcinoma [48]
• Patients with only one first order relative with a history of colorectal cancer, could be followed using combined barium enema and flexible sigmoidoscopy at five-year intervals [39]
• If two related second degree relatives with colorectal cancer at any age, risk is equivalent to one affected first degree relative
• If person has one second degree relative or any third degree relative(s) with colorectal cancer screen as average risk. Individualized evaluation, including a careful family history, is encouraged
• If patient has first degree relative with adenoma(s), colonoscopy beginning at age 50 or at the age of diagnosis of the adenoma in the relative, whichever is earlier, repeat after 5 – 10 year (Consider the shorter interval when advanced or multiple adenomas are diagnosed prior to age 60 y) [48]
• Recommend repeating the flexible sigmoidoscopy or colonoscopy screening at five-year intervals in patients having adenomatous polyposis [39]
• If patient is a gene carrier or at risk for familial adenomatous polyposis (Includes the subcategories of familial adenomatous polyposis, Gardner syndrome, some Turcot syndrome families, and attenuated adenomatous polyposis coli) advise sigmoidoscopy annually, beginning at age 10 to 12 years or colonoscopy in case of AAPC starting at the age of 20 yrs and continued until age 35 to 40 if negative [39].
• If patient has > 100 polyps in colon or > 20 cumulative adenomas in colon, advise genetic testing for FAP [39]
• If person is a first degree relative of FAP or AFAP patient, advise genetic testing [39]
• If person has a family history of FAP, advise genetic studies in an affected family member. Others should be tested for the same gene [39]
• If no gene mutation is identified all members of family at high risk should undergo screening [39]
• If patient has FAP screening of the upper gastrointestinal tract with upper endoscopy for gastric and duodenal polyps has been recommended [40]
• Careful palpation of the thyroid is recommended annually for all patients with FAP, including asymptomatic gene carriers [41].
• If children are at risk for FAP, should undergo testing for serum alpha-fetoprotein and have abdominal palpation every six months until the age of six. Serum alpha-fetoprotein is elevated in approximately two-thirds of patients with a hepatoblastoma [42].
• Patients who have undergone colectomy remain at risk for the development of adenomas and adenocarcinoma in the ileum [42]
• Colectomy at the time of initial diagnosis is strongly recommended in patients with multiple large (>1 cm) adenomas or adenomas with villous histology and/or high grade dysplasia and is the safest approach of all those with profuse polyposis at initial diagnosis [43].
• Patients in the second decade of life with only sparse, small (<5 mm) adenomas can usually be followed endoscopically with surgery scheduled to accommodate school and work schedules [43].
• If patient is a gene carrier or at risk for hereditary non-polyposis colorectal cancer advise colonoscopy, every 1 to 2 years, beginning at age 20 to 25 years or 10 years younger than the earliest diagnosis in the family, whichever comes first. HNPCC more commonly involves proximal colon [44]
• If gene can be found in patient with HNPCC advise demonstration of a mutated gene can then be used to screen the remainder of the family, and identify those members who need intensive monitoring [45].
• If patient has HNPCC gene annual screening for endometrial and ovarian cancer beginning at age 25 to 35 years (pelvic examination and endometrial aspirate with or without transvaginal ultrasound) is also recommended. Discussion of prophylactic hysterectomy and salpingo-oopherectomy at around age 35 or at the end of childbearing [46].
• If patient has HNPCC gene advise annual urinalysis and cytologic examination beginning at age 25 [46]
• If patient has HNPCC gene annual skin surveillance is advised [46]
• If patient has HNPCC gene advice periodic upper endoscopy. It should be performed in all patients starting at age 30 [47]

American Joint Committee on Cancer (AJCC) TNM Staging

System for Colorectal Cancer

Primary Tumor (T)

Regional Lymph Nodes (N)

Distant Metastasis (M)

Stage Grouping

TX Primary tumor cannot be assessed

T0 No evidence of primary tumor

Tis Carcinoma : intraepithelial or invasion of lamina propria

T1 Tumor invades submucosa

T2 Tumor invades muscularis propria

T3 Tumor invades through the muscularis propria into the subserosa,

or into non-peritonealized pericolic or perirectal tissues

T4 Tumor directly invades other organs or structures, and/or perforates visceral peritoneum

NX Regional lymph nodes cannot be assessed

N0 No regional lymph node metastasis

N1 Metastasis in 1 to 3 regional lymph nodes

N2 Metastasis in 4 or more regional lymph nodes

MX Distant metastasis cannot be assessed

M0 No distant metastasis

M1 Distant metastasis

STAGE GROUPING [56]

Stage T N M Dukes MAC

0 Tis N0 M0 - -

I T1 N0 M0 A A

T2 N0 M0 A B1

IIA T3 N0 M0 B B2

IIB T4 N0 M0 B B3

IIIA T1-T2 N1 M0 C C1

IIIB T3-T4 N1 M0 C C2/C3

IIIC Any T N2 M0 C C1/C2/C3

IV Any T Any N M1 - D

· If the cancer is localized to the mucosa and submucosa, patient is said to have Dukes' A or TNM stage I [35]

· If the cancer is extending into or through the muscle layer without lymph node involvement patient is said to be in Dukes' B or TNM stage II [35]

· If there is lymph node involvement patient is said to be in Dukes' C or TNM stage III [35]

· If patient has distant metastases patient is said to be in Dukes' D or TNM stage IV [35]

SCREENING

• If person is 50 - 80 years of age having no personal or family history of colorectal carcinoma (Not having the following: A first degree relative or two second degree relatives with colorectal cancer, or clustering of HNPCC related cancers in the family) or no family history of adenomatous polyps before age of 60 yrs and no history of inflammatory bowel disease, advise cancer surveillance by either flexible sigmoidoscopy every 5 years, annual fecal occult blood test (FOBT), combination of flexible sigmoidoscopy or colonoscopy every 5 years and annual FOBT or total colon evaluation [32, 48]

• If patient is African American 45 to 80 years old having no personal or family history of colorectal carcinoma or no family history of adenomatous polyps before age of 60 yrs, advise cancer survillance by either flexible sigmoidoscopy every 5 years, annual fecal occult blood test (FOBT), combination of flexible sigmoidoscopy or colonoscopy every 5 years and annual FOBT or total colon evaluation [32]
• If colonoscopy is done (which is preferable if available) and is negative having no mass or polyps, repeat colonoscopy after 10 years. [48]
• If colonoscopy shows polyps recommend colonoscopic removal and histopathology of the specimen
• If polyp is hyperplastic advise routine colonoscopy after every 10 years. [48]
• If patient has polyp (adenoma with villous component, or any adenomatous polyp greater than 10 mm) or prior colorectal cancer advise colonoscopic surveillance at a 3- to 5-year interval [32]
• If patient has an abnormal sigmoidoscopy with significant pathology (single adenoma >1.0 cm, adenomas with tubulovillous or villous histology, or multiple adenomas) advise colonoscopy [37]
• If patient has an abnormal sigmoidoscopy with adenomas 0.6 to 1.0 cm, and for those with multiple adenomas advise colonoscopy
• For those with single tubular adenomas <0.6>
• If fecal occult blood is advised to the patient, ask the patient to take the diet having no red meat or turnip/horseradishes (to prevent false-positive peroxidase reactions); no gastric irritant drugs (to prevent false-positive reactions from gastritis); no vitamin C (to prevent a false-negative chemical reaction); and high-fiber foods (to increase stool transit time) [36].
• If any sample of FOBT is positive proceed as follows [48]

Any positive test requires evaluation

3 successive stool specimens should be examined

Repeat test after prescribed diet

Sample not digital rectal examination

Guaiac-based nonrehydrated test should be performed

Immunochemical techniques are under investigation

Test should be coordinated by health care provider

Annual FOBT need not be performed if screening colonoscopy or doublecontrast enema is used as a screening measure in an average-risk patient

.

• If FOBT positive and colonoscopy negative, proceed with additional workup
• If patient has long standing inflammatory bowel disease involving the colon advise colonoscopic surveillance at a 1 to 2-year interval starting at 8 - 10 years from disease onset [32, 48]
• When clinically quiescent, 4 quadrant biopsies every 10 cm with > 30 total samples using large cup forceps (preferred). Additional extensive sampling of strictures and masses is also advised.
• Endoscopic polypectomy when appropriate with biopsies of surrounding mucosa for the assessment of dysplasia [48]
• The finding of definite dysplasia (of any grade) should be confirmed by an expert pathologist and is an indication for colectomy [38]
• Patients whose biopsies are indefinite for low grade dysplasia after review by an expert pathologist should undergo repeat surveillance colonoscopy at a shorter interval.

• If patient has High-grade dysplasia/intraepithelial neoplasia or Multifocal low-grade dysplasia/intraepithelial neoplasia, prophylactic proctocolectomy with ileoanal pouch should be considered [48]

• If patient has a family history of colorectal cancer they can be familial adenomatous polyposis, attenuated familial adenomatous polposis or othe varients and heridiatry non polyposis colorectal carcinoma.
• If patient has a family history of colorectal cancer involving one first order relative diagnosed before age 60, two first order relatives diagnosed at any age or a single first order relative diagnosed after age 60 advise colonoscopic surveillance at a 1- to 5-year interval begin at age 40 or 10 years before the index carcinoma [48]
• Patients with only one first order relative with a history of colorectal cancer, could be followed using combined barium enema and flexible sigmoidoscopy at five-year intervals [39]
• If two related second degree relatives with colorectal cancer at any age, risk is equivalent to one affected first degree relative
• If person has one second degree relative or any third degree relative(s) with colorectal cancer screen as average risk. Individualized evaluation, including a careful family history, is encouraged
• If patient has first degree relative with adenoma(s), colonoscopy beginning at age 50 or at the age of diagnosis of the adenoma in the relative, whichever is earlier, repeat after 5 – 10 year (Consider the shorter interval when advanced or multiple adenomas are diagnosed prior to age 60 y) [48]
• Recommend repeating the flexible sigmoidoscopy or colonoscopy screening at five-year intervals in patients having adenomatous polyposis [39]
• If patient is a gene carrier or at risk for familial adenomatous polyposis (Includes the subcategories of familial adenomatous polyposis, Gardner syndrome, some Turcot syndrome families, and attenuated adenomatous polyposis coli) advise sigmoidoscopy annually, beginning at age 10 to 12 years or colonoscopy in case of AAPC starting at the age of 20 yrs and continued until age 35 to 40 if negative [39].
• If patient has > 100 polyps in colon or > 20 cumulative adenomas in colon, advise genetic testing for FAP [39]
• If person is a first degree relative of FAP or AFAP patient, advise genetic testing [39]
• If person has a family history of FAP, advise genetic studies in an affected family member. Others should be tested for the same gene [39]
• If no gene mutation is identified all members of family at high risk should undergo screening [39]
• If patient has FAP screening of the upper gastrointestinal tract with upper endoscopy for gastric and duodenal polyps has been recommended [40]
• Careful palpation of the thyroid is recommended annually for all patients with FAP, including asymptomatic gene carriers [41].
• If children are at risk for FAP, should undergo testing for serum alpha-fetoprotein and have abdominal palpation every six months until the age of six. Serum alpha-fetoprotein is elevated in approximately two-thirds of patients with a hepatoblastoma [42].
• Patients who have undergone colectomy remain at risk for the development of adenomas and adenocarcinoma in the ileum [42]
• Colectomy at the time of initial diagnosis is strongly recommended in patients with multiple large (>1 cm) adenomas or adenomas with villous histology and/or high grade dysplasia and is the safest approach of all those with profuse polyposis at initial diagnosis [43].
• Patients in the second decade of life with only sparse, small (<5 style="color:green">43].
• If patient is a gene carrier or at risk for hereditary non-polyposis colorectal cancer advise colonoscopy, every 1 to 2 years, beginning at age 20 to 25 years or 10 years younger than the earliest diagnosis in the family, whichever comes first. HNPCC more commonly involves proximal colon [44]
• If gene can be found in patient with HNPCC advise demonstration of a mutated gene can then be used to screen the remainder of the family, and identify those members who need intensive monitoring [45].
• If patient has HNPCC gene annual screening for endometrial and ovarian cancer beginning at age 25 to 35 years (pelvic examination and endometrial aspirate with or without transvaginal ultrasound) is also recommended. Discussion of prophylactic hysterectomy and salpingo-oopherectomy at around age 35 or at the end of childbearing [46].
• If patient has HNPCC gene advise annual urinalysis and cytologic examination beginning at age 25 [46]
• If patient has HNPCC gene annual skin surveillance is advised [46]
• If patient has HNPCC gene advice periodic upper endoscopy. It should be performed in all patients starting at age 30 [47]

DIFFRENTIAL DIAGNOSIS

• Diverticular disease.
• Irritable bowel syndrome.
• Inflammatory bowel disease.
• Local rectal pathology. E.g. hemorrhoids.
• Ischemic colitis.
• Infective colitis
• Pneumatosis coli.
• Endometriosis
• Solitary rectal ulcer

If patient has mass in colon it should be differentiated from

• Tuberculosis
• Amebiasis
• Cytomegalovirus
• Fungal infections
• Extrinsic lesions

INVESTIGATIONS

• If CRC is suspected advise full blood count
• If CRC is suspected also advise liver function tests.
• If patient has ca colon advise X Ray chest
• Digital rectal examination and proctoscopy with or without sigmoidoscopy if available should be done but this should not delay definitive investigations.
• Flexible sigmoidoscope can reach deep enough into the bowel to detect about 60% of tumors [31].
• If screening sigmoidoscopy discloses a large adenoma (>1.0 cm), or adenomas of any size with tubulovillous or villous histology, or multiple adenomas; sigmoidoscopy should be followed by colonoscopy in these circumstances [33].
• Colonoscopy is the gold standard for diagnosis of colorectal cancer. At colonoscopy, up to 30% of subjects with distal colonic neoplasms have proximal lesions (up to 20% of these may be advanced) [30].
• If malignant obstruction precludes a full colonoscopy preoperatively, it should be carried out at a later time
• Attempt biopsy of every polyp under 5 mm in diameter. Polyps larger than 10 mm should be referred for complete excision at colonoscopy (no biopsy needed). Intermediate-sized polyps (greater than 5 mm and less than 10 mm) may be referred for colonoscopic removal [30]
• If the polyp was biopsied at flexible sigmoidoscopy and is hyperplastic on histology, no further exam is needed at this screening. Nonadenomatous polyps (juvenile, hyperplastic, lipomatous, inflammatory) have no precancerous potential and do not require referral for colonoscopy [30].
• If the colonoscopy is inadequate due to a partially obstructing lesion that precludes a more proximal advance of the colonoscope, the more proximal colon should be evaluated by radiologic means like CT colonography where available and if not available, use of a contrast enema to evaluate the more proximal colon is advised [32].
• Barium enema may be used if colonoscopy fails to visualise the caecum and/or the patient is unable to tolerate the procedure.
• Liver ultrasound, (occasionally intrarectal ultrasound) and CT or MRI is useful in staging. MRI is more specific than CT in showing liver metastases [22].
• Positron emission tomography (PET) is valuable for detection of recurrent colorectal cancer, but has little effect on staging of primary cancer [22].
• No consensus has been reached about the most sensitive method for detection of liver metastases of colorectal cancer. A meta-analysis [22] showed that PET is the most sensitive modality, and is also especially valuable for detection of extrahepatic disease. However, no randomised study has yet proved the value of PET in this setting, and therefore, CT and MRI remains the diagnostic standards.
• For patients with symptoms or a rising serum CEA level who is suspected of having metastatic disease but whose diagnostic workup is negative, PET scanning can potentially localize occult disease, permitting the selection of patients who may benefit from exploratory laparotomy [34].
• Elevated pre-treatment serum levels of carcinoembryonic antigen (CEA) have a negative prognostic significance (CEA is no use in screening but can be helpful in predicting relapse in patients after surgery suitable for further resection).
• If CEA is > 3 ng/ml in on smokers or > 5 ngram/ml in smokers, consider patient may have ca colon or rectum. It may also be raised in people with cancer of the pancreas, breast, ovary, or lung. CEA can also be elevated in cirrhosis, pancreatitis, kidney failure, inflammatory bowel disease, peptic ulcer disease, chronic obstructive pulmonary disease (COPD), or an obstructed bile duct.

STAGING

If patient is diagnosed to have ca colon determine the local and distant extent of disease spread in order to provide a framework for discussing therapy and prognosis by examining the biopsy specimen, having abdominopelvic ultrasonography/ CT for disease extent and X Ray chest for secondaries:

Criteria for urgent referral in patient suspected of CRC include

• Patients over the age of 50 years with any of the following symptoms over a period of six weeks should be urgently and appropriately investigated:
• Rectal bleeding with a change in bowel habit to looseness or increased frequency.
• Rectal bleeding without anal symptoms.
• Palpable abdominal or rectal mass.
• A definite palpable right-sided abdominal mass
• Intestinal obstruction.
• A definite palpable rectal mass (not pelvic)
• All patients with iron-deficiency anemia (below 10 Grams in post-menopausal women and below 11 Grams in all men) without other obvious cause should be thoroughly investigated for colorectal cancer.

METASTASIS

• If patient has colorectal carcinoma, because the venous drainage of the intestinal tract is via the portal system, the first site of hematogenous dissemination is usually liver, followed by lungs, bone, and many other sites, including brain [25]
• If the tumor arises in the distal rectum, it may metastasize initially to the lungs because the inferior rectal vein drains into the inferior vena cava rather than into the portal venous system [25]