COLORECTAL CANCER (CRC)

Colorectal cancer is the third most commonly diagnosed cancer in men and women (after prostate and lung cancer among men and after breast and lung cancer among women). Usually it occurs in the age of 50-60

60% of colorectal cancer is detected in the distal colon, 1/3 in rectum. In general, CRC have 4 types

1.Polypoid: often located on the right side of the colon, causing bleeding.

2 Infiltrating: often located on the left side of the colon, leading to obstruction.

3 Ulcers: Located mostly in the cecum.

4 Nodular

5% of the cases takes the form of (synchronous) multiple primary colon cancer. Mostly evolve from such precancerous pathologies as family polyposis or ulcerative colitis.

 

Risk Factors

Diet: In developed countries colorectal cancer is more common. This situation is associated with diet rich of animal protein and fat in comparison to high-fiber nutrition in developing countries.

Bile acids: There is correlation between the concentration of bile acids: mainly lithocholic acid (LCA) and deoxycholic acid (DOC) and the colorectal cancer incidence.

Genetic factors: There is no convincing evidence of genetic inheritance, but genetic predisposition is possible. It is known that the simultaneous presence of two factors such as cancer in the family history (+) and age over 50 increases the risk.

Risk of CRC in people with a negative family history is classified at the level of 1.0. People with a history of colorectal cancer in a first-degree relative are at increased risk - 1.8. The risk is even higher if more than one first-degree relative was diagnosed with cancer - 2.75 if one of those relatives was younger than 45 the risk increases to 5.75.

It is also known that the tumor suppressor gene p53 mutation affect the transformation of adenoma to cancer.

Inflammatory and polypoid lesions: Many hereditary diseases increase the risk of colorectal cancer. Family polyposis is one of them. Polyps are not visible from birth, but they occure at the age of about 20, without treatment they evolve in to CRC.

Gardner's syndrome is a form of family polyposis that causes non-cancer tumors of the skin, soft tissue, bones and desmoid tumors in the mesentery of the small intestine,

Turcot syndrome is a rare inherited condition, which is linked to adenomatous polyps, colorectal cancer and malignant tumors of the central nervous system.

Petz-Jeghers syndrome manifests itself with type of polyp in the gastrointestinal tract called hamartomatous polyps and lesions of the mucous membranes of the mouth and lips, and sometimes also the dorsal feet and hands.

10% of polyps greater than 1 cm becomes an invasive cancer. While some of these tumors are treated with colonoscopic polypectomy other due to lymph nodes metastasis require segmental resection

 

Prevention

75% of the colorectal cancer cases develop in patients whit predisposing factors. For this reason very important are regular screenings for CRC. The prognosis of cancers in its early stage is better than in advanced stage.

In the colorectal cancer screening following tests are included:

1- Fecal occult blood

2- Double contrast colon radiography

3- Sigmoidoscopy

4- Colonoscopy

 

Symptoms

Change in bowel habits, change in the abundance of his stool and bleeding are the most common symptoms of CRC but the clinical presentation of the tumor often depends on its location, size, and degree of spread.

Tumors of the right colon are usually chronic, cause slow bleeding, which leads to anemia, which is a primary reason of admission to hospital. In this patients fecal occult blood analysis should be done, because bleeding usually appears intermittently. If during the examination patient feels pain tumor is suspected. Generally in these cases bowel habits are not changed, but sometimes the mucus-secreting tumors can cause diarrhea. Obstruction in right colon cancers occurs less frequently in comparison to left colon tumors due to the large diameter of the lumen and a greater content of fluid

Tumors of the left side of the colon cause change in bowel habits and the size of the stool. It may cause painful bowel movements. Patients are usually admitted to hospital after obstruction.

Rectal cancer cause complaints of rectal bleeding more often than on the obstruction

 

Physical Examination

Physical signs of colorectal cancer can include distension, increase bowel sounds, or the symptoms of peritonitis.

Evaluation of patient with CRC

X-ray image of the abdominal cavity can show layers of air or fluid, distension of the small intestine and free gas below the diaphragm.

Colonoscopy: type of screening test that allows to evaluate entire length of the colon and rectum with a colonoscope, a thin, flexible, lighted tube with a small video camera on the end. during a colonoscopy special tools can be passed through the colonoscope to perform a biopsy or remove suspicious tissue.

Rigid proctosigmoidoscopy: Allows to evaluate the rectum and about 20 – 25 cm of sigmoid colon The doctor can look closely at the inside lining of the rectum through the scope. The tumor can be seen, measured, and its exact location can be determined.

Ultrasonography is generally use to control the abdominal spread.

Computed tomography and MRI: According to some new schools are not carried out in the pre-operative period. Because during the operation, even in a patient with metastatic disease, it’s more important to remove the primary tumor than to prevent complications such as bleeding and obstruction.

Laboratory tests that support the diagnostic process include tumor markers. The most common tumor markers for colorectal cancer is carcinoembryonic antigen (CEA)

 

Treatment

Surgical Treatment

Surgery is aimed to remove the lesion with the mesentery and lymph nodes. To obtain sufficient results tumor must be removed together with the 2 cm of surrounding healthy tissue. However, in advanced stages, the degree of intraluminal spread comes up to 4 cm. Proximal and distal border of procedure should be define using the frozen section.

In case of colorectal cancer complications (perforation, obstruction, bleeding) to decrease the risk of intra-abdominal infection and morbidity it is necessary to apply intestinal cleansing before surgery.

In obstruction and unresectable cases, as palliative care proximal colostomy is applied.

Surgical treatment of rectal cancer unlike to treatment of colon cancer leads to serious morbidity and decreases life quality (diet or permanent stoma, after abdomioperineal resection - APR).

 

Nowadays in the early stages of the cancer in the distal part of colon doctors recommend local treatment instead of radical surgery as the APR.

There are 3 main methods of colorectal cancer treatment.

* Local Therapies

Transanal excision

Transanal endoscopic microsurgery

Intracavitary radiation

*Low anterior resection

 

Adjuvant therapy

In 30-50% of colorectal cancer cases local and distant recurrences are observed. Most distant metastasis are detected in the liver. Distant metastases after surgery develop from already existing micrometastasis. Adjuvant chemotherapy is directed to them. For patients with colon cancer III stage and high risk II stage most optimal is adjuvant treatment, these patients should be referred for clinical studies.

 

Radiotherapy

It is used in preoperative stage to reduce tumor size and invasion degree, what increases the success of the operation and reduces the risk of recurrence. Preoperative radiotherapy also reduces the risk of the spread during the operation. Postoperative radiotherapy reduces the risk of local recurrence. Application of adjuvan radiotherapy depends on lesions location. In colon cancer, due to mobility and number of adjacent organs adjuvant radiotherapy is not recommended, but in cases of estraperitoneal location of rectal tumors radiation therapy can be very effective.

 

Chemotherapy, Immunotherapy

The most frequent combination is 5 FU with other targeted drugs. Chemoimmunotherapy increases survival rate in a serious degree.

 

Prognosis

Prognosis of CRC is not commensurate with the size of the detected tumors. On the prognosis affects the degree of tumors penetration in the intestinal wall and nodal involvement.

Only 57% of patient with well-differentiated tumors stay alive 5 year after diagnose (relative survival rate) in the case of poor-differentiated tumors survival rate falls to 35%. Life expectancy depends on stage of disease.

Stage 0 75-80%

Stage 1 74%

Stage 2 63%

Stage 3 46%

Stage 4 6%

 

Recurrence

It is important to make the control biochemical tests, ultrasonography, and colonoscopy at certain time intervals after surgical treatment.

Generally, treatment of colorectal cancer recurrence is difficult. In that case surgery usually is performed for complications and isolated liver metastases.