Colorectal cancer commonly seen in diabetic men

Colorectal cancer commonly seen in diabetic men

                The colon and rectum perform vital functions in the last phases of digestion. Digestion first begins in the mouth where food is chewed into smaller pieces and swallowed. The food travels down the esophagus to the stomach where it is further broken down by gastric juices and sent to the small intestine. The small intestine continues to break down the contents in addition to absorbing most of the nutrients, including carbohydrates, proteins and vitamins. Once the contents have passed through the small intestine, the material has become mostly liquid and is moved into the colon, which measures about 5 ½ feet long. The main function of the colon is to absorb water and dehydrate the leftover material, forming semi-solid matter, or stool. The colon moves the stool into the approximately 6-inch long rectum, which acts as a holding chamber, until it is ready to be expelled through the anus.

                                                Because colon and rectal cancers arise from the same type of cell and have many similarities, they are often referred to collectively as “colorectal cancer”. The cells lining the colon or rectum can sometimes become abnormal and divide rapidly. These cells can form benign (non-cancerous) tumours or growths called polyps. Although not all polyps will develop into colorectal cancer, colorectal cancer almost always develops from a polyp. Over a period of many years, a polyp’s cells may undergo a series of DNA changes that cause them to become malignant (cancerous). At first, these cancer cells are contained on the surface of a polyp, but can grow into the wall of the colon or rectum where they can gain access to blood and lymph vessels. Once this happens, the cancer can spread to lymph nodes and other organs, such as the liver or lungs—this process is called metastasis, and tumours found in distant organs are called metastases ^[1]. There are usually no symptoms in early stages

                                                  Studies in swedan at karolinska institute in Stockholm and University of California Berkeley. (The findings were  published in the journal  Diabetes Care, the American Journal of Gastroenterology)noted that there is a link between colorectal cancer and diabetics^{[ 2  ]}. Men with diabetics may want to be more vigilant about screening for cancer,and had an elevated risk of colorectal cancer..   Study researchers from above universities surmise that the results show a relationship between insulin resistance (the inability of the body to use insulin properly) and colorectal cancer. "These observations support the hypothesis that hyperinsulinemia or factors associated with insulin resistance…may play a role in colorectal carcinogenesis.

                                                    They tracked more than 45,000 men between the ages of 45 and 79. They found 411 cases of colorectal cancer developed among the group over an average six-year period. After factoring in a number of variables, the researchers discovered that having diabetes was associated with nearly a 50% increased risk of developing colon and rectal cancer..The study authors noted additional insulin-connected factors that are closely related to an increased risk for colorectal cancer.                                              

                                                 Dietary and lifestyle factors related to insulin resistance and hyperinsulinemia, including a westernized diet, physical inactivity and obesity, have been linked to (an) increased colorectal cancer risk. Also, a recent study reported that chronic insulin therapy was related to a significant increased risk of colorectal cancer among patients with type 2 diabetes ^[3]

                                                    Although diabetes appears to be associated with colon cancer in some capacity, it appears that the relationship is not as serious as was once thought. The American Cancer Society conducted a study demonstrating that men with diabetes had a 25% increase in risk of colon cancer, but that risk was less severe than scientists had previously thought. In addition, research has not proven that the same link between diabetes and colon cancer also exists in women ^[3].

SPREAD:-

1) Direct spread-Spreads most commonly by direct extension in both ways-circumferentially into bowel as well as directly into depth of bowel wall to serosa, and sometimes into peritoneal cavity.

2) Lymphatic spread-Spread via lymphatics occurs involves firstly the regional lymph nodes in vanity of tumor, and then into other groups of lymph nodes like preaortic, internal iliac and sacral lymph nodes.

3) Haematogenous spread-Blood spread of large bowel cancer occurs relatively late and involves the liver, lungs, brain, bones and ovary ^[4].

TREATMENT OF COLORECTAL CANCER:-

1] Surgery

Surgery with curative intent is primary treatment modality for stage 1, 2 and 3 colorectal cancers.

2] Adjuvant therapy

The administration of treatment aimed at occult microscopic disease that may remain after complete surgical resection of all gross disease is termed adjuvant therapy. The goal of treatment when no disease is present to decrease the risk of recurrences and ultimately prolong survival. To obtain maximal benefit, the adjuvant therapy should be administer when potential tumour burden is minimal and must be administered in maximally tolerated doses.

3] Radiation

Radiation therapy is sometimes used in patients with colon cancer. It is usually used in combination with chemotherapy for patients with stage III rectal cancer. For patients with stage IV disease that has spread to the liver, treatments directed at the liver can be used. This may include: Burning the cancer (ablation), Delivering chemotherapy or radiation directly into the liver, freezing the cancer (cryotherapy).

4] Advanced colorectal cancer for stageⅳ

A) Chemotherapy:-

Chemotherapy is used to improve symptoms and prolong survival in patients with stage IV colon cancer. Chemotherapy is usually the only feasible approach to controlling advanced (stage ⅳ) colorectal cancer. It has no curative potential in an attempt to decrease symptoms and ultimately prolong survival

B) Combination chemotherapy:-

Numerous combinations of chemotherapeutic agents have been explored in colorectal cancer. Monoclonal antibodies, including cetuximab (Erbitux), panitumumab (Vectibix), bevacizumab (Avastin), 5-fu, cisplatin, cyclophosphamide and other drugs have been used alone or in combination with chemotherapy.

5] Future therapies

Irinotecan is first line therapy for colorectal cancer revealed response rate of 19-32%.Irinotecan as second line treatment of 5-fu resistant colorectal carcinoma resulted in response rate of 13-25%.It is approved by FDA as standard second line treatment for patients with colorectal cancer. Recommended dose is 125mg/m² IV weekly times for every six weeks. Toxicities of irinotecan are diarrhea, nausea, myelosuppression.An alternative irinotecan dosing schedule of 350mg/m² IV every 3 weeks has approved for use in us. Toxicity with this regimen is similar to weekly schedule. The fluropyramidines continue to be the most active and most commonly used agents used in colorectal cancer ^[5].

RECENTLY APPROVED DRUGS BY FDA FOR COLORECTAL CANCER:-

The FDA announced a new form of avastin together with Oxaliphan chemotherapy for those suffering from colorectal cancer.Avastin is only available through prescription and is only for intravenous infusion. It is a form of biological antibody that is designed to bind specifically to protein known as vascular endothelial growth factor, which plays an integral part in life cycle of cancer tumour.

In September 28, 2012 a new drug called Stivarga (regorafenib) to treat patient with colorectal cancer was approved. The drug was evaluated in a clinical study of 760 patients who had previously been treated for metastatic colon cancer. Patients treated with Stivarga lived an average 6.4 months, compared to 5 months for patients who received a placebo^[6].

The drug works by blocking several enzymes in the body that help cancer cells grow. It’s the second drug approved for colon and rectal cancer in the past two months. The FDA approved Zaltrap (ziv-aflibercept) in August.

A warning to be included in the drug’s prescribing information states that severe and sometimes fatal liver toxicity occurred in some patients treated with Stivarga during the clinical study. Other side effects can include weakness or fatigue, loss of appetite, hand-foot rash, diarrhoea, mouth sores, weight loss, infection, high blood pressure, and voice changes^[7][6].

Shilpa, Second Pharm.D