Description of Colorectal Cancer Pathogenesis

1. Describe the pathogenesis of Brian’s colorectal cancer from the initial cellular mutation to the diagnosis of stage IIA colorectal cancer.

2. Describe two (2) modiflable and three (3) non-modifiable risk factors for colorectal cancer and expalain how these risk factors may have contributed to the development of Brian’s colorectal cancer.

1. Colorectal cancer refers to the development of cancer in the colon or rectum part of a large intestine. The risk is less associated with a genetic factor (20 % of cases). On the contrary, it is more likely to link with older age, lifestyle including smoking, regular alcohol consumption, lack of physical activity and frequent intake of red meat.

Epithelial cell lining in the colon or rectum region has link with the pathogenesis of colorectal cancer. Mutation in the Wnt signaling pathway which results in increased signaling activity is the basic reason. APC (adenomatous polyposis cold) gene is responsible for expression of APC protein, which prevents the accumulation of β-catenin protein. Mutation in this gene produces faulty protein, because of which high level of accumulation of β-catenin protein occurs in cells (Rosty, 2013). This protein has potential to enter the nucleus and binds to DNA, and triggers the transcription of proto-oncogenes. Normally these genes are important for renewal of stem cell and corresponding differentiation. In high expression condition, they lead to cancer. P53 protein in cell functions for monitoring of cell division and apoptosis. Mutation in Wnt signaling leads to transformation of tissue into benign epithelial tumor to invasive epithelial cancer. Defects in another gene such as AXIN1, NKD1, TGF-β and SMAD also leads to stimulation of oncogene, leading to cause cancer-like condition (Zhu, 2013).

Presence of individual cell and small tumor cells at the invasive front of carcinoma is known as tumor budding stage. The risk of colorectal cancer stages is defined by TNM staging. With the cancer is touching the inner lining of the bowel, it is known as T stage. Condition where the cancer cell is invasive to the inner lining of the bowel, it is referred to as stage II, or Duke Stage B in clinical terms of colorectal carcinoma. Soon after this stage, the cancer cells become more invasive to bowel (Fearon, 2011).

2. Modifiable risk factors:

Smoking – smoking offers the prospect of genetic mutation that is responsible for various other forms of cancer including lung cancer and colorectal cancer. The risk factor associated with smokers is approximately five times higher compared to non-smokers for colorectal cancer. Often after diagnosis, general physician recommend quitting smoking that along with proper treatment have potential to restore the health conditions (Parajuli, 2013).

Lack of physical activity – the lack of physical activity has potential to deteriorate the health conditions in varieties of ways.  The condition of physical activity often leads to obesity, cardiovascular disorder, and improper circulation. Apart from this, reduced activity also helps in inefficient clearance of metabolites and toxic byproducts from the body that aid in risk of colorectal cancer. People who are not physical active, have a greater risk of developing the colorectal cancer, which can be recovered with proper treatment and increase in physical activities (Morikawa, 2013).

Modifiable Risk Factors of Colorectal Cancer

Non-modifiable risk factors:

Age – It is noteworthy to mention that chances of developing colorectal cancer are persistent in young adults also, but the risk of developing after the age of 50 increases. There are evidences that among ten cases of diagnosis, where colorectal cancer is confirmed, and nine cases are associated with older people with age more than 50 years old (Siegel, 2012).

Personal history of inflammatory bowel disease (IBD) – IBD includes Crohn’s disease and ulcerative colitis, where colon uses to have inflammation for a longer time. People are suffering from IBD often develop the condition of dysplasia, where cell lining of colon or rectum looks abnormal and are prone to develop cancer with time (Thomson, 2014). Hence, screening is necessary in such condition, which was there in Brain’s case.

Inherited syndrome – Chances are there that Brain might have inherited gene defect that have the probability to give rise to family cancer syndrome. Inherited syndrome associated with colon cancer is adenomatous polyposis and nonpolyposis colorectal cancer. Owing to these inherited gene defect, chances are there, that with age, signaling defect incurves the cancer complication.

Metronidazole is a broad spectrum drug that has “civil” activity against protozoa. It enters the cell by diffusion and produces nitro radical that act as an electron sink against anaerobic organism.  It also controls bowel movement along with preventing the infection in the colorectal region. In operative case, often pouchitis is necessary for which metronidazole is effective in preventing bowel complication. Notably, low dose Metronidazole is effective for chronic term as required in the present condition of Brain’s treatment (Vaughan-Shaw, 2013).

Morphine is the principal drug necessary for the management of pain. It exerts the action with interaction with opioid receptors present in neurons, CNS, and peripheral tissues. Upon acting over µ and δ receptor, it reduces the motility in the gastrointestinal tract. More importantly, it reliefs from pain especially the pressure ulcer pain, that is obvious after the operative condition. Since opium has dependency characteristics and carriers several legal obligation for its usage, thus effective medication management is necessary, in this case (Holler, 2013).

• Controlled analgesia is useful following the surgical conditions, but is also effective in the management of cancer-related
• Morphine is the gold standard for intravenous analgesia and hence is the opioid of choice.
• Mediation management requires proper chart preparation and approval by the pain control service council of the concerned health care settings.
• Use of patient-controlled analgesia requires specifically designed locked pump as continuous infusion rate, which allows bolus dose and lockout interval during a specific period. The dose concentration and interval of administration should be restricted to four hour period (Day, 2012).
• Importantly, only trained nurses should handle this activity with utmost care and safety.
• In PCA, Patient should be supplied with button to press for self-administer the amount of intravenous or subcutaneous analgesic solution (bolus dose). Such pump programming helps in determining the time for another bolus dose (Levv, 2011).
• Use of other medication should be cross-referred with evidence-based method for any drug or food related adverse effects.
• Level of consciousness should be monitored, as it will help in deciding the dose close to the monitoring process for any complication.
• PCA is suitable for daytime management; it is hence nurse controlled analgesia might be necessary for night time. It is thus necessary to use evidence-based practice and discussion with other professionals.
• Baseline observation needed with administration a valid pain assessment; heart rate, respiratory rate, blood pressure and the baseline sedation score.

References:

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Fearon, E. R. (2011). Molecular genetics of colorectal cancer. Annual Review of Pathology: Mechanisms of Disease, 6, 479-507.

Holler, J. P., Ahlbrandt, J., Burkhardt, E., Gruss, M., Röhrig, R., Knapheide, J., … & Weigand, M. A. (2013). Peridural analgesia may affect long-term survival in patients with colorectal cancer after surgery (PACO-RAS-Study): an analysis of a cancer registry. Annals of surgery, 258(6), 989-993.

Levy, B. F., Scott, M. J., Fawcett, W., Fry, C., & Rockall, T. A. (2011). Randomized clinical trial of epidural, spinal or patientâ€Âcontrolled analgesia for patients undergoing laparoscopic colorectal surgery. British Journal of Surgery, 98(8), 1068-1078.

Morikawa, T., Kuchiba, A., Lochhead, P., Nishihara, R., Yamauchi, M., Imamura, Y., … & Ogino, S. (2013). Prospective analysis of body mass index, physical activity, and colorectal cancer risk associated with β-catenin (CTNNB1) status. Cancer research, 73(5), 1600-1610.

Parajuli, R., Bjerkaas, E., Tverdal, A., Selmer, R., Le Marchand, L., Weiderpass, E., & Gram, I. T. (2013). The increased risk of colon cancer due to cigarette smoking may be greater in women than men. Cancer Epidemiology Biomarkers & Prevention, 22(5), 862-871.

Rosty, C., Hewett, D. G., Brown, I. S., Leggett, B. A., & Whitehall, V. L. (2013). Serrated polyps of the large intestine: current understanding of diagnosis, pathogenesis, and clinical management. Journal of gastroenterology, 48(3), 287-302.

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Vaughan-Shaw, P. G., Borley, N. R., Tomlinson, I. P., & Wheeler, J. M. (2013). PTH-011 Polypectomy May Lead to Inadequate Surveillance of Patients with a Family History of Colorectal Cancer. Gut, 62(Suppl 1), A216-A216.

Zhu, Q. C., Gao, R. Y., Wu, W., & Qin, H. L. (2013). Epithelial-mesenchymal transition and its role in the pathogenesis of colorectal cancer. Asian Pac J Cancer Prev, 14(5), 2689-98.