Pathophysiology

Genetically, colon cancer is a complex disease, and occurs due to genetic changes associated
with the development of premalignant lesions (adenomas) to invasive adenocarcinomas.[2]

The beginning is the existence of an APC (adenomatous polyposis gene) mutation, which was
first discovered in individuals with Familial Adenomatous Polyposis (FAP). This protein
coded by APC is important in the activation of c-myc oncogens and cyclin D1, which
promotes development into a malignant phenotype. Although FAP is a rare hereditary
syndrome that accounts for only about 1% of cases of colon cancer, APC mutations are also
very common in sporadic colon cancer. [1]

Other important genes in carcinogenesis in the colon include: KRAS oncogene, loss of
chromosome heterozygosity 18 which causes inactivation of the SMAD4 gene (DPC4), and
tumor suppressor gene DCC (which is a deletion in colon cancer). In addition, deletion of the
17p chromosome arm and mutation of the suppressor gene p53 tumor cause cell resistance to
programmed cell death (apoptosis) and this is considered to be an advanced event in colon
carcinogenesis. [1]

A number of colon cancers are also characterized by lack of DNA mismatch repair. This
phenotype is associated with gene mutations such as MSH2, MLH1, and PMS2. This
mutation produces what is called high frequency microsatellite instability (H-MSI), which
can be detected by immunocytochemical testing. H-MSI is a hallmark of hereditary
nonpolyposis colon cancer syndrome (HNPCC, Lynch syndrome), which accounts for about
6% of all colon cancers. H-MSI is also found in about 20% of sporadic colon cancers. [1]

Clinical Presentation

Because of increased attention on screening in clinics, colon cancer is now often detected
before it starts causing symptoms. In further cases, clinical presentations that can occur
include iron deficiency anemia, rectal bleeding, abdominal pain, changes in bowel habits, and
bowel obstruction or perforation. Right-sided colon lesions are more likely to bleed and cause
diarrhea, whereas tumors in the left-sided colon are usually detected at an advanced stage and
can appear as intestinal obstruction. [1]

Physical examination findings can be fatigue, weight loss, or normal early in the course of
colon cancer. In more advanced cases, a sign may appear: [1]
• Abdominal pain during palpation
• Anal bleeding that is macroscopic
• Palpable abdominal mass during palpation
• Hepatomegaly
• Ascites

Diagnosis

Suspicion in the diagnosis of colon cancer requires a colonoscopy examination with a biopsy
of any suspicious lesion. The National Comprehensive Cancer Network recommends that all
patients under the age of 70 who are diagnosed with colorectal cancer be tested for hereditary
nonpolyposis colon cancer syndrome (HNPCC, Lynch syndrome). Whereas patients aged 70
and over are only tested if they meet the revised Bethesda guidelines for HNPCC. [11, 12]

After tissue diagnosis (histopathology) is confirmed, laboratory studies are carried out with
the aim of assessing the function of the patient's organs (liver, kidney) in anticipation of
diagnostic and therapeutic procedures and also to estimate tumor burden. Adequate imaging
of the chest and abdomen must be obtained for staging purposes, ideally before surgery. [1]

One important laboratory examination is CEA. An initial CEA level must be obtained before
surgery because it carries a prognostic value and when very high can indicate further disease
and metastasis. Increased serum CEA levels are associated with a poor prognosis in patients
with operable colon cancer. [13]
Adequate chest and stomach imaging must be obtained for staging purposes. Generally an
abdominal CT scan is performed to evaluate the abdomen and liver. As for the evaluation of
pulmonary metastases, imaging can be done in the form of chest radiograph or chest CT scan.
[1]

Positron Emission Tomography (PET) scan is a very useful modality for staging and
evaluating colon cancer. The combination PET-CT scan, makes it possible to detect
metastatic deposits and has an additional tissue-based resolution of CT. However, please
note, some histology of colon cancer, especially mucinous signet-ring cell variants, cannot be
visualized properly with PET scans. [1]

Screening
In the United States, there are joint guidelines developed by the American Cancer Society,
the US Multi-Society Task Force on Colorectal Cancer, and the American College of
Radiology. [14] These guidelines recommend that screening for colon cancer and
adenomatous polyps begin at the age of 50 in asymptomatic men and women. The screening
includes:
• Sigmoidoscopy is flexible every 5 years
• Colonoscopy every 10 years
• Barium double contrast enemas every 5 years
• CT colonography every 5 years

Flexible Sigmoidoscopy
Flexible sigmoidoscopy screening every 5 years causes a reduction in CRC mortality and use
of high-risk individuals with adenomas. In patients with polyps, cancer or other
sigmoidoscopy flexion, get a colonoscopy.

Colonoscopy
Colonoscopy is currently the most accurate and best method used in examining the large
intestine. This procedure is very sensitive in detecting even small polyps and can be biopsy,
polypectomy, control bleeding and stricture dilatation. However, this examination requires
intestinal preparation and causes discomfort because it requires sedation. Colonoscopy is
done with the help of endoscopy. The main complications after colonoscopy are perforation
and bleeding, but they are very small.
The view of Colonoscopy and Sigmoidoscop