Epidemiology and Pathogenesis
• It is the 3rd most common cancer in the world in general. It is the most common GI cancer.
• As with other GIS cancers, the risk begins to increase over the age of 45-50 and continues to increase in direct proportion to age.
• APC (tumor suppressor) gene inactivation is the most common (85%) and first mutation in sporadic colorectal cancers.
• In the trough that started with the APC mutation; Beta catenin, COX-2, KRAS, DCC, p53 gene mutations play a role.
• DNA repair gene mutations in the other pathway; MSH2, MLHL, PMS2 mutations play a role. This pathway plays a role in 15% of non-APC cancers.
• Cancer can develop from the plain colonic mucosa as well as from the adenomatous polyp background. These polyps may develop sporadically, especially over the age of 50, or may be associated with familial polyposis syndromes.
Colon Polyps
• They are considered the most common benign tumors of the colon.
• Polyps are classified according to their histological structures and malignant potential as follows:
Non-neoplastic (hyperplastic, inflammatory, hamartomatous)
Hyperplastic polyps and inflammatory polyps are considered non-malignant.
Hamartomatous polyps are also known as non-neoplastic, but multiple
Malignancy has been reported in some familial syndromes with hamartomatous polyps.
Neoplastic polyps (adenoma)
These polyps can be tubular, villous adenoma, or tubulovillous.
The risk of malignancy increases as the villous component and diameter increase.
The diameter of the polyp and the degree of dysplasia are the most important determinants of malignancy risk.
Serrated polyp: A group of lesions with serrated epithelium in the colon are defined as serrated polyps. These;
Hyperplastic polyps (no risk of malignancy)
Sessile serrated adenomas (risk of malignancy)
• Factors determining the risk of malignancy in adenomas
Histology (villous > tubulovillous > tubular)
Morphology (sound > stem)
Number (the higher the number, the greater the risk)
Size(> 2.5 cm polyp cancer risk >= 10%)
Dysplasia (cancer risk: low grade 6%, high grade 35%)
• In a patient with adenomatous polyp detected in colonoscopy, the entire colon must be seen.
Polyposis syndromes
• They are frequently familial and autosomal dominant syndromes characterized by multiple polyps in the colon and other parts of the GIS.
• In these syndromes, the polyps are either adenomatous or hamartomatous.
• Some are accompanied by extraintestinal findings and tumors.
• Familial (familial) adenomatous polyposis (polyposis coli, classical FAP)
It is the most common familial polyposis syndrome.
OD is inherited and develops as a result of APC gene mutation on chromosome 5. The diagnosis is made by the presence of > 100 adenomatous polyps in the colon and a positive family history.
Polyps begin to appear from puberty and the risk of malignancy reaches 40 years of age.
up to close to 100%. Tumors are mostly seen in the left colon.
In general, the risk of malignancy begins at the age of 15-20 years, so proctocolectomy should be performed when the diagnosis is made in adults.
It is recommended to start screening programs at the age of 10-12 years and with annual sigmoidoscopy. Gene mutation analysis and retinal pigment epithelial hypertrophy can be used in the evaluation of suspected patients, but they are not sufficient for screening.
In these patients, the most common cause of death other than colon cancer is intra-abdominal desmoid tumors.
The subtype of FAP, which is characterized by less than 100 adenomatous polyps in the colon and leads to cancer development in older ages (after 50 years), is defined as "attenuated FAP" (mild FAP) and is seen less frequently. Tumors tend to be localized to the right colon, unlike classical FAP.
• Gardner and Turcot syndrome
There is an APC gene mutation and is also known as the FAP variant.
Gardner's syndrome; It progresses with mandibular osteoma, soft tissue tumors, adenomatous polyposis in the colon and small intestine, ampullary tumor, teeth more than normal, desmoid tumors and congenital hypertrophy of retinal pigment epithelium.
Turcot syndrome; CNS tumors progress with multiple adenomatous polyps in the colon.
• Peutz-Jeghers syndrome
It is characterized by mucocutaneous hyperpigmentation and multiple hamartomatous polyps in the GIS. Polyps are most commonly located in the small intestine. Breast cancer is the most common and colon cancer is the second most common in these patients. It is the disease that increases the risk of pancreatic cancer the most.
• Juvenile polyposis
It progresses with multiple hamartomatous intestinal polyps.
Although it is low, there is a risk of developing colon cancer.
• Cowden's syndrome
It is characterized by multiple hamartomatous polyps in the colon, facial trichilemmoma, keratosis of the hands and feet. There is a low risk of developing colon cancer in this disease. Breast and thyroid cancer risk is high.
• Cronkhite-Canada syndrome
It progresses with hamartomatous polyps in the colon, alopecia, nail dystrophy, skin hyperpigmentation; rarely becomes malignant. It is not familial.
• Hereditary non-polyposis colon cancer (Lynch syndrome)
OD is inherited and is the most common hereditary colon cancer.
Hereditary, one of which is first degree; It is characterized by (1) having colon cancer in at least 3 relatives, (2) occurring in at least two consecutive generations, and (3) having at least one case under 50 years of age.
The mean age of tumors is less than 50 years and is more common in the proximal colon. The most common extracolonic tumors in these patients are endometrial and ovarian tumors. There may be tumors of the stomach, pancreas, bile.
There are mutations in DNA repair genes. (MLHI, MSH2)
These family members should be screened with a colonoscopy every two years starting from the age of 25.
Causes That Increase the Risk of Colon Cancer
• Age (>45) and family history
• diet; a diet rich in animal fats, low in fiber, excess red meat, and high in calories
• History of radiotherapy to the pelvis
• Presence of adenoma before
• Smoking and alcohol use
• Obesity
• Hereditary polyposis syndromes, Lynch syndrome
• Inflammatory bowel diseases
• Streptococcus bovis bacteremia
• Ureterosigmoidostomy
Factors That May Be Protective For Colon Cancer
• Long-term use of aspirin and NSAIDs
• Regular physical activity
• Postmenopausal hormone replacement therapy
• diet; A diet rich in vegetables and fruits, fibrous foods, calcium, folate and methionine.
Pathology and Clinic
• The most common malignant tumor is adenocarcinoma and is most commonly located in the rectosigmoid region (35-40%), least in the descending colon.
• The most common metastases are to regional lymph nodes and liver.
• Cancers on the right are less symptomatic and mostly present with symptoms of anemia and weight loss due to occult bleeding, while cancers on the left are more symptomatic and present with obstruction and constipation, decreased stool caliber, rectal bleeding and tenesm.
• In general, the first and most common symptoms in colon cancers are changes in bowel habits. However, patients may neglect this and the most common reason for coming to the clinic is rectal bleeding and tenesm.
Screening and Diagnosis
• Screening tests are recommended for people at risk and adults over the age of 50 for the early diagnosis of colon cancer.
• Screening programs recommended for healthy individuals;
Hidden blood in stool determination (annual)
Sigmoidoscopy (5 years apart)
Colonoscopy (10 years apart) (most effective method)
A patient with suspected colon cancer in clinical evaluation or other testing should undergo a direct colonoscopy.
• Diagnosis is made by colonoscopy + biopsy.
Serum CEA determination should be made. However, its value in early diagnosis is limited. They are used to monitor response to treatment and identify recurrences.
Staging
• Staging in colon cancers is similar to other GIS tumors.
• Rectal endosonography is the most valuable in determining local spread in tumors involving the rectum.
• Computed tomography is used to identify distant metastases.
• While the TNM staging system can be used, which provides a more detailed assessment, Dukes staging is common in practice because it is simple and practical.
