Introduction
Colorectal cancer is a type of cancer that occurs in the colon and rectum. The most prevalent form of gastrointestinal cancer is colorectal cancer (AlSohaily, Biankin, Leong, KohonenCorish, & Warusavitarne, 2012). It is linked to substantial morbidity and mortality all over the world. According to research, it is the third most prevalent cancer in men and the second most common cancer in women around the world (Siegel, DeSantis, & Jemal, 2014). Its prevalence, on the other hand, is about equivalent in all genders. It is the second leading source of cancer-related mortality in men in the United States (Siegel et al., 2014). It is most widespread in Australia and New Zealand (DeSantis et al., 2014). On the contrary, lower prevalence has been reported in India, South America, Africa and South Central Asia (DeSantis et al., 2014).
Epidemiology and Risk Factors
The frequency of colorectal cancer peaks in individuals above 50 years (Ahnen et al., 2014). The median age at diagnosis is 67 years (Siegel et al., 2014). Previously, less than 19% of cases occurred before the age of 50 years (Ahnen et al., 2014). However, currently, there are concerns over the increased rates of occurrence of colorectal cancer among young and middle-aged adults in the US. Research showed that for adults between the age of 20 to approximately 40 years, the incidence rates for colorectal cancer have increased by 1% annually from the mid-1980s to 2014 while for individuals between 41-55 years, the rate increased by 0.5% (Siegel et al., 2014). Siegel et al. (2014) further showed that people born in the 1990s have a 2-4 times risk of colorectal cancer than individuals born in the 1950s. Besides, mortality rates for colorectal cancer have been on an annual rise for individuals below the age of 55 years (Ahnen et al., 2014).
Risk Factors
Several risk factors are implicated in colorectal cancer. They include environmental influences, genetic factors, and gastrointestinal inflammatory conditions. As mentioned earlier, people above 50 years of age are at a higher risk of colorectal cancer. Johnson et al. (2013) note that people who have previously been treated for colorectal cancer or adenomatous polyps are also at risk. Specific hereditary syndromes are associated with increased risk for colorectal cancer. These include lynch syndrome and familial adenomatous polyposis where individuals with the former bear a risk of 45% within their lifetime while for the latter, there is almost a 99% likelihood of getting colon cancer by the age of 40 years (Johnson et al., 2013). A family history of the malignancy also increases the risk of colorectal cancer. Inflammatory conditions such as Crohn’s and ulcerative colitis carry a risk for colon cancer (Jess, Rungoe, & Peyrin–Biroulet, 2012). The risk increases with the duration of inflammation and the extent of colonic involvement. Dietary factors that increase the risk include a low intake of fruits and vegetables, intake of low fiber diets, and a high intake of red meat and refined fats and carbohydrates. Johnson et al. (2013) further note that lifestyle choices including smoking and alcohol consumption, obesity, and a sedentary lifestyle are risk factors for colorectal cancer. The effect of body sizes is particularly remarkable in men where it has been shown to affect the process of carcinogenesis, especially in its early stages. Lastly, diabetes and previous radiation therapy to the abdomen for cancer are also implicated (Johnson et al., 2013).
Anatomy and Physiology
The large bowel is a hollow tube sheathed in a serosal layer. It has a critical role in the formation and storage of stool. The colon absorbs water, electrolytes such as chloride ions, and vitamin K produced by the flora in the colon (Jayasekeran, Holt, & Bourke, 2013). Anatomically, the colon is divided into proximal and distal segments. The proximal sections are the ascending and transverse colon while the distal portion is made of the descending and sigmoid colon (Jayasekeran et al., 2013). Histologically, different layers of tissue make up the wall of the colon and rectum. The mucosa contains the epithelial cells. Most colorectal cancers, adenocarcinomas, arise from these epithelial cells (Al–Sohaily et al., 2012). Most colorectal cancers begin as polyps- growths in the inner lining of the colon and rectum. The chances of developing into cancer depend on whether the polyp is benign or cancerous. In this regard, polyps can be adenomatous (adenoma) which are mostly carcinogenic, or hyperplastic-these are more common and mostly harmless. Other factors such as the number of the polyps found, their sizes, or if they are dysplastic as well as other risk factors outlined above determine the potential for malignancy.
Genetic and Molecular Basis
Both genetic and epigenetic defects are responsible for the molecular events that lead to colorectal adenocarcinoma. Early events involve a mutation in the APC gene ("adenomatous polyposis gene") (Al–Sohaily et al., 2012). They can be inherited or acquired mutations. The gene codes for APC protein. The APC protein negatively regulates the β-catenin protein (Bogaert, & Prenen, 2014). Mutations and epigenetic events functionally inactivate the APC gene. With the functional inactivation of APC, there is accumulation of β-catenin (Bogaert, & Prenen, 2014). β-catenin is translocated into the nucleus where it activates gene transcription. The genes transcribed in this case are proto-oncogenes which promote uncontrolled proliferation of cells. Mutation of KRAS proto-oncogene, for instance, results in the loss of controlled cell growth and apoptosis (Bogaert, & Prenen, 2014). Other variations involve tumor suppressor genes such as p53. Abnormal DNA methylation, an epigenetic event, is also implicated in colorectal cancer. It leads to the activation of oncogenes and stifling of tumor suppressor genes (Al–Sohaily et al., 2012). In this way, the genetic balance is compromised, which is followed by malignant transformation. Other epigenetic abnormalities involve a deficiency in DNA mismatch repair. The deficiency is caused by a loss of mismatch repair genes. Consequently, a condition termed microsatellite instability results. Microsatellite instability is the basis for Lynch Syndrome, which is associated with a risk of colon cancer (Al–Sohaily et al., 2012).
Clinical Considerations
Signs and Symptoms
These include a change in bowel habits, which may entail changes in stool consistency, diarrhea, or constipation lasting for more than a month (Van Cutsem, Cervantes, Nordlinger, & Arnold, 2014). Blood in the stool may be indicative of rectal bleeding. Abdominal discomfort includes episodes of a feeling of fullness, gas, or pain (Van Cutsem et al., 2014). Other vague signs and symptoms include weakness, fatigue, and unexplained weight loss.
Diagnosis
After a comprehensive physical examination, different laboratory and imaging studies may be indicated for diagnosis. Laboratory studies include blood tests for anemia and tests for tumor markers such as carcinoembryonic antigen (CEA) (Van Cutsem et al., 2014). Colonoscopy helps to pinpoint polyps, remove them, and pick samples for biopsy (Van Cutsem et al., 2014). If one has cancer, elicited from pathological biopsy examination, imaging studies are used to facilitate tumor staging.
Prognosis
It depends on prognostic factors such as the stage of the disease, serum levels of CEA pretreatment, the level of lymph node involvement, and distant metastasis (DeSantis et al., 2014). The five-year survival rates differ depending on the prognostic factors. In the US, for example, the five-year survival rate for all stages is 66% (DeSantis et al., 2014).
Treatment
Different modalities of treatment of colorectal cancer depend on the stage of the disease. Stages I-III are curable with surgery (Breugom et al., 2015). Surgical resection is also used for stage IV cancer with minimal metastasis to the liver and lungs (Breugom et al., 2015). Adjuvant chemotherapy is also incorporated in stage III disease (Breugom et al., 2015). Radiation therapy, another treatment modality, is mostly limited to palliative therapy in cases of metastasis to the brain or bones.
Surgery
The main goal of surgery is the removal of the primary tumor and the adjacent tissue margins as well as the neighboring draining lymph nodes (Breugom et al., 2015). Further, it aims at reconstructing the bowel if it is possible to regain its maximum possible functioning postoperatively. There are several surgical options. As an example, laparoscopic surgery is a surgical treatment modality. It is a minimally invasive type of surgery that involves making small incisions on the abdomen and inserting several viewing scopes into the abdomen followed by correction of cancer (Van Cutsem et al., 2014). In cases of rectal cancer, a colostomy may be indicated. It is a surgical operation that creates an opening called a stoma on the abdomen. A stoma can be permanent or temporary. It connects the large intestine with the abdominal surface where a pouch worn by the patient is used to collect stool (Van Cutsem et al., 2014).
Radiation Therapy
It uses beams of X-rays to kill the cancer cells. Its role in colon cancer is limited despite being a standard modality of treatment of rectal cancer. However, where the tumor has metastasized to the liver and/or lungs, forms of radiation therapy such as brachytherapy and stereotactic radiation therapy may be utilized (Breugom et al., 2015). A radiation therapy regimen entails a series of sessions of treatment given over a specified period. Radiation therapy may be used to shrink large tumor masses before surgery for easier removal, to alleviate cancer symptoms, or even after surgery to remove any remaining neoplastic cells (Breugom et al., 2015). Another minimally invasive procedure is ablation. Radiofrequency ablation uses energy in the form of radiofrequency waves to heat the tumor mass (Breugom et al., 2015). It removes tumors which have metastasized to the liver or lungs. Cryotherapy, another thermal ablation technique, uses probes that freeze the tumor mass and the surrounding liver parenchyma (Breugom et al., 2015).
Chemotherapy
It involves the use of drugs to kill the cancer cells. It hinders the ability of the cancers cells to grow and divide (Breugom et al., 2015). Systemic chemotherapy is administered intravenously or orally. A chemotherapy regimen consists of some cycles conducted over a specific period. In colon cancer, chemotherapeutic agents are administered after surgery, especially if the regional lymph nodes were involved, to prevent the chances of cancer recurrence (Van Cutsem et al., 2014). Examples of agents used include tipiracil/trifluridine, capecitabine, irinotecan, etc. (Van Cutsem et al., 2014).
Opinion
The use of surgery as a treatment modality confers the advantage of its ability to reach body areas that would otherwise be inaccessible using chemotherapy and radiotherapy (Breugom et al., 2015). Besides, new microsurgical procedures that are minimally invasive make it a safe form of treatment. Also, surgery is a prerequisite during diagnosis, that is when obtaining tissue biopsies. Consequently, operations allow for a comprehensive medical examination of the cancerous tissues to determine the best course of treatment. It, however, has some disadvantages such as surgical complications pre- and postoperatively, an inability to treat metastatic tumors, and the risk of cancer recurrence, which necessitates the use of other treatment options (Breugom et al., 2015). Radiotherapy confers the advantage of its ability to kill even the microscopic tumor cells that may be unnoticeable during surgical resection (Breugom et al., 2015). It also preserves organs that would otherwise have been resected using surgical techniques. However, rays used in radiation therapy may destroy surrounding body organs. It also has side effects such as nausea, vomiting, and skin reactions. A significant advantage of chemotherapy is its ability to kill cancer cells in broad areas of the body, unlike surgery and radiotherapy which focus on one specific area (Breugom et al., 2015). It, therefore, kills many cancer cells both in the primary tumor and the disseminated ones. Its main disadvantage, however, is the systemic toxicities associated with the use of chemotherapy. In other cases, innate resistance develops against the chemotherapeutic agents (Breugom et al., 2015). Besides, chemotherapy often requires combination with different treatment modalities. Therefore, surgery, currently, is the preferred modality of treatment for colorectal cancer. However, the utility of surgical operations may differ depending on the stage of the disease which may further necessitate its combination with other modalities for maximum efficacy.
Conclusion
Colorectal cancer is the most common gastrointestinal malignancy. Its incidence varies globally but is highest in Australia and New Zealand. Its development is a multifactorial disease process involving different risk factors coupled with ranging genetic and epigenetic defects. The most common error is a mutation in the APC gene. Various signs and symptoms are highlighted as well as its diagnosis and prognosis. Of the different treatment modalities, surgery is the most preferred especially in localized disease. However, the utility of surgery may be reinforced using other treatment modalities to improve the outcomes of the treatment process.
References
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