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Colorectal Cancer Paper

Colorectal Cancer

            Colorectal cancer can be described as a malignant neoplasm of the colon, rectum and anal canal (Wells 2006). Colorectal cancers arise from colonic adenomatous polyps. These polyps are usually benign but they may become malignant due to the level of risk propagated by either genetic or environmental predisposing factors.

Etiology

            The etiology of colorectal cancer is very complex and involves an interplay of genetic and environmental factors. In combination these factors conspire to alter anatomically normal mucosa to an abnormal premalignant adenomatous polyp. Over the course of many years, this premalignancy progresses to colorectal cancer.

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            Familial factors have been demonstrated to significantly contribute to the risks associated with the sporadic development of colorectal cancer. While these genetic linkages mean that the likelihood of developing cancer before the risky age is increased, an enhancement to the risk of developing premalignant adenomas occurs when there is a genetic linkage to first degree relatives harboring colorectal cancer. In provocative assessments of groups, results suggest a dominant inherited susceptibility to the development of sporadic colorectal cancer. But the incidence of colorectal cancer as a product of genetic predisposition is variable depending on the extent of exposure to environmental factors. Specifically, genetic polymorphisms in glutathione-S-transferase, N-acetyltransferases (NAT1, NAT2), and ethylenetetrahydrofolate reductase, are of paramount importance. These polymorphisms are variable with respect to ethnicity and race. This explains why colorectal cancer is geographically variable (DeVita et al 2008).

            Even though greatly underscored in several seminal studies, environmental factors play a role in increasing the incidence and prevalence of colorectal cancer. Diet has a strong association with colorectal cancer. Total calorie intake and obesity are two independent and interrelated factors for the development and progression of colorectal cancer. Increase in body mass by  two fold increases the risk for colorectal cancer. This risk is more pronounced among men with colon cancer as opposed to rectal cancer.

            The ingestion of red meat increases the risk to colorectal cancer. Since the consumption of red meat is closely related to the socioeconomic status of an individual, per capita consumption is a potent risk indicator. However, research about the abstinence from red meat consumption and its effect in lowering the risk to colorectal cancer has not been conclusively studied. What is certain is that barbecued, fried and processed meat poses individuals to greater risk. Dietary intake rich in high fiber affords protection to colorectal cancer. The protective effects of fruits and vegetables is not uncontested as there is enough evidence suggesting that antioxidant vitamins, thioethers, foliate, terpenes, and plant phenols possess chemoprotective and carcinoprotective effects (DeVita et al 2008).

            Physical inactivity has a strong association with the development of colorectal cancer, especially colon cancer. Individuals having a sedentary lifestyle predispose themselves to cancer. Alcohol consumption has a predisposing effect to colorectal cancer. In a panel report by WCRF, evidence incriminating alcohol intake with the increase in colorectal cancer risk was found. Other studies have demonstrated a dose dependent alcohol consumption with colorectal cancer even when carcinoprotective factors are incorporated in the study(Longnecker et al 1992). This causal association needs further research so as to specifically determine the levels of dosage and risk (Kune et al 1987; DeVita et al 2008).

Incidence

            It is estimated that there are approximately 0.8 million new cases of colorectal cancer cases; 153, 760 in the United States. This estimate accounts for a tenth of all incident cancers. Mortality from this disease is nearly 0.45 million annually with 52,180 deaths occurring in the United States in 2003 (DeVita et al 2008). these statistics attest to the gravity of colorectal cancer on global health outcomes. The prevalence of harboring invasive colorectal cancer among individuals aged fifty years and above lies in the range of 0.5- 2% (DeVita et al 2008). More than any other demographic factor, the impact of age on the incidence of colorectal cancer is so predominant. After the age of 45 years, sporadic occurrence of cancer increases.

            Adenocarcinoma of the rectum and the colon is ranked second as the cause of cancer related deaths in U. S (Aziz & Wu 2001). The incidence of this adenocarcinoma increases with the increase in age in equal frequency among men and women. Below forty years the occurrence of colorectal cancer is uncommon. However, this changes sharply after the 50 year mark. Since the 1980s incidence of colorectal cancer has been on a steady decline mainly owing to the current strategies employed in polyp removal, early detection, accurate diagnosis and effective treatment interventions. Rates in the developing worlds are fairly higher than those in the developed world due environmental and dietary differences (Aziz & Wu 2001).

Signs and Symptoms of Colorectal Cancer

            Signs and symptoms are extremely subtle, varied and mostly nonspecific. Early stages are asymptomatic and diagnosis can only be made through screening (Wells 2006). In most cases, these adenomas are largely asymptomatic but when symptoms occur they usually possess a relationship to occult or overt rectal bleeding (Scheppach et al 2003). The initial symptoms of colorectal cancer are usually vague and not entirely descriptive of the condition. These symptoms include; weight loss, fatigue and bleeding. Local symptoms are usually rare in the premalignancy stage. These symptoms become apparent as the tumor continues to grow large. As the tumor enlarges towards the anus, bowel symptoms become apparent. Generally, symptoms are categorized as local, constitutional and metastatic.

            Local symptoms include; changes in bowel frequency such as diarrhea and or constipation, tenesmus, bloody stools, mucous stools and melena. Bowel obstruction occurs as the size of the tumor increases causing pain, vomiting of stool like substances and bloating. With time patients can feel a tumor in their abdomen. If the cancer invades the bladder, symptoms such as hematuria and pneumaturia may be detected. Vaginal invasion occasions maloderous vaginal discharge. However, these symptoms are representative of the late stage of tumor development (Wells 2006).

            Constitutional symptoms are sometimes referred to as systemic symptoms. They include unexplained weight loss that is usually a result of lack of appetite as well as the systemic effects of the malignancy.  Weight loss alone does not infer that an individual is suffering specifically from colorectal cancer.   Weight loss is also representative of other carcinomas.  Pallor and blood tests can be carried out to confirm the reduction of hemoglobin level. Anemia, fatigue and palpitations are some of the constitutional symptoms of colorectal carcinoma.

            Liver metastases causes’ jaundice abdominal pain mainly anterior of the epigastrium or in other cases pain may be felt at the right side of the abdomen. Clinical analysis by the doctor will confirm hepatomegally (liver enlargement). Blood clot in the arteries and veins is caused by a paraneoplastic syndrome. This syndrome has strong association to blood hypercoagulability.

            Hematochezia occurs in the descending colon, sigmoid as well as the rectum. Melena is closely associated with the right colon. In comparison to overt bleeding, occult bleeding is more predominant in the right and left sided adenomas. Since it is much hidden, occult bleeding can occur for a considerably long period of time before it is recognized until symptoms of iron deficiency anemia develop. It is only in rare cases, that adenomas present with symptoms associated to partial obstruction of the bowel (Scheppach et al 2003).

Radiographic Manifestations of Colorectal Cancer.

            Idiopathic inflammatory bowel diseases (IBDs) are definitive of any disease affecting the GIT. These diseases are often associated with a wide range of other systemic complications. These complications constitute the extra intestinal manifestations of IBDs. Specifically referred to as immune-mediated phenomena, these complications have been used as  direct pathophysiologic indicators of bowel inflammation or disease. Like all IBDs, colorectal cancers also exhibit these extra intestinal manifestations which can be detected radiographically (Hauser et al 2004).

            The most common chemical marker for colorectal cancer is the carcinoembronic antigen (CEA). This is a glycoprotein resident in cell membranes of tissues, colorectal cancerous tissue included. Once it enters into circulation it can be detected by serum radioimmunoassay. Even though, CEA is detectable in almost all body fluids, gastrointestinal cancers, a host of benign diseases and nonalimentary cancers lead to the rise of CEA in blood serum. Approximately 70% of all patients suffering from cancer have high levels of CEA. This makes this glycoprotein a useful marker in radiographic screening techniques. However, due to its non-specificity it is not a reliable diagnostic test but it is very useful in detecting the recurrence of cancer following curative surgical resection (Doherty et al 2005).

            Radiographic manifestations can also be obtained by routinely carrying out barium enema examination. This technique is important in diagnosis of colorectal cancer however it is unnecessary in where complete colonoscopy has been performed. Cancer in the left colon always appear as a fixed filling defect measuring two to four centimeters long with an annular configuration. Lesions in the right colon appear as an intraluminal mass or a constriction. These images are typical of an advanced carcinoma. Earlier stages are best diagnosed through colonoscopy. X-rays are not reliable in colorectal cancer detections. Palpation are endoscopy are more reliable diagnostic techniques.

            Computed tomography scans are more essential in assessing extramural extensions among patients with rectal cancers but not cancer of the colon. CT scans detect recurrence and metastases in rectal cancer. MRI and PET scans are more useful in elucidating and providing accurate diagnostic information for virtually all cancers (Doherty et al 2005).

Diagnosis

            Colorectal cancer s takes extremely long timely periods to develop. Early detections are central to the chances of a successful therapeutic management. In case colorectal cancer is suspected, physicians should carry out a careful history of the patient and carry out physical examinations with the aim of identifying the risk factors and the clinical manifestations of colorectal carcinoma. Through protosigmoidoscopy or colonoscopy, the entire large bowel is evaluated with double contrast barium enema (Wells 2003).

            Baseline laboratory tests include complete prothrombin time (PT), blood cell count, serum carcinoembronic antigen (CEA) , renal and liver function tests. Serum carcinoembronic antigen aids as a marker in both diagnosis and in the monitoring of treatment response. Despite this usefulness Serum CEA is non specific and too insensitive when screening early stage colorectal cancer. Tests such as radiographic imaging have grown to become central diagnostic options for cancers. X-rays, abdominal computed tomography, magnetic resonance imaging and ultrasonography can be employed especially in the early detection of colorectal carcinomas. The use of tumor directed antibodies in the immunodetection of tumors is important in early detections of these cancers. As the disease progresses, these tests are important in the identification of recurrent disease or metastatic cancers which are always manifested through rising CEA levels (Lang et al 2004).

Treatment and Complications

            Appropriate diagnosis is central to the commencement of an appropriate treatment program. Usually diagnosis should be able to define the stage of the disease: I, II and three can be cured, stage IV is incurable. Treatment in stage four is aimed at prolonging survival, alleviating the symptoms and managing the associated complications. Based on the diagnostic criteria, the treatment modalities with favorable outcomes are radiation therapy, surgery, biomodulators and chemotherapy (Wells 2006). Surgery is the most common treatment option in patients with colorectal cancer.

            Basically, surgery as categorized into curative, bypass, fecal diversion, palliative or open and close surgeries. Curative surgery is the most preferred surgical option if the tumor is localized. At the onset of cancer development, the cancerous cells inside the polyp can be eliminated by polypeptomy during colonoscopy. In a more advanced age of colonic cancer, surgical treatment involves the removal of the tumor containing colon with sufficient margin, colectomy and if possible anastomosis of the remnant parts of the colon to facilitate the regain of physiological function. In most cases, curative surgery involves the total mesorectal excision or abdominoperineal excisison (Ko et al 2008).

            The progression to multiple metastases, call on primary tumor palliative surgery(palliative resection). This is done to reduce morbidity due to invasion, bleeding and the catabolic effects of colorectal tumor. Through improved chemotherapeutic interventions, isolated liver metastases can be removed through surgery. In circumstances where the tumor has invaded adjacent structures, excision becomes technically difficult and the only option for surgeons is a proximal fecal diversion or ileotransverse bypass. The worst case of colorectal surgical treatment is when the tumor is unresectable. In this case open and close surgery is performed. However, the later surgical procedure is often avoided at all costs. Moreover, laparascopic assisted colectomy; an advanced surgical option is preferred because it is minimally invasive (Ko et al 2008).

            Just like any surgical operation, this treatment option may occasion complications. The most common complications are anastomosis breakdown resulting to fistula formation or abscess and peritonitis. Wound infections, hernia and dehiscence coupled to excessive bleeding are fatal complications if not immediately and adequately managed. There are cases where adhesions after surgery may result to bowel obstruction. Other complications are grouped under cardiorespiratory complications and they include, pneumonia, arrhythmia, myocardial infarction and pulmonary embolism. Injuries to adjacent organs may also occur. Since it is very difficult for patients to return to their normal lifestyles after the completion of surgery, specially trained enterstomal therapists help patients to adjust in the shortest time possible(Lee & Marks 2007).

            Chemotherapy is another treatment option used to prevent the development of metastasis. Chemotherapeutic interventions slows down tumor growth or shrinks it. It is often applied adjuvant or neo-adjuvant to surgery. In some cases it is used as a palliative option. Adjuvant chemotherapy involves a single regimen of a combination of oxiplatin, leucovorin and 5-flourouracil. For a metastatic stage chemotherapy regimens use a combination of infusional  oxiplatin, leucovorin and 5-flourouracil with bevacizumab (Ko et al 2008).

            Radiotherapy is most common in colon cancer where it serves as palliation and pain relief. In rectal cancer it is administered neo-adjuvant. In addition to these treatment interventions, other support therapies such as social service support, counseling and other services help in mitigating most difficulties arising from colorectal cancer. Radiotherapies predispose an individual to highly potential ionizing radiation and therefore they should be done with utmost care both for the radiographer and the patient under radiotherapy (Ko et al 2008).

Prognosis
The rates of survival of patients with colorectal cancer are directly related to the time of detection and carcinoma type. For those diagnosed during their early stages, their survival rates are five times the late stage detections. The concentration of CEA in serum is used in the prognosis of the disease. The concentration of CEA is directly proportional to the bulk of tumor tissue. Follow ups should be done to prevent the recurrence of met or the development of tumors originating from the metachronous lesions.

Summary

            Colorectal cancer can be described as a malignant neoplasm of the colon, rectum and anal canal. Colorectal cancers arise from colonic adenomatous polyps. These polyps are usually benign but they may become malignant due to the level of risk propagated by either genetic or environmental predisposing factors. The etiology of colorectal cancer is very complex and involves an interplay of genetic and environmental factors. In combination these factors conspire to anatomically alter normal mucosa to an abnormal premalignant edenomatous polyp. Over the course of many years, this premalignancy progresses to colorectal cancer. Familial factors have been demonstrated to significantly contribute to the risks associated with the sporadic development of colorectal cancer.

            Environmental factors play a role in increasing the incidence and prevalence of colorectal cancer. Diet, alcohol consumption and physical inactivity. Statistics attest to the gravity of colonic cancer which comes second in mortality rates of cancer related diseases. Early stage colorectal carcinoma is asymptomatic but as it progresses diagnosis can be done by colonoscopy, barium enema and a host of other radiographic techniques. The treatment of cancer is dependent on the stage of the disease. During the early stages: I, II and III, colorectal cancer is curable but stage VI is highly advanced and can only be managed. Surgical removal of cancerous tumors remains the major treatment option. However, chemotherapeutic interventions and radiotherapy are also profoundly important. The rates of survival of patients with colorectal cancer are directly related to the time of detection and carcinoma type. For those diagnosed during their early stages, their survival rates are five times the late stage detections. The concentration of CEA in serum is used in the prognosis of the disease. The concentration of CEA is directly proportional to the bulk of tumor tissue. Follow ups should be done to prevent the recurrence of met or the development of tumors originating from the metachronous lesions.

References

Aziz, K. & Wu, Y. George. (2001). Cancer Screening: A Practical Guide for Physicians.             Humana Press. 87

DeVita, T. Vincent., Lawrence, S. Theodore., Rosenburg, A. Steven., Weiberg., DePinho, A.      Robert. (2008). DeVita, Hellman, and Rosenberg’s Cancer: Principles & Practice of         Oncology. Lippincott Williams & Wilkins. 1233-1241

Doherty, M. Gerard., Way, W. Lawrence. (2005). Current Surgical Diagnosis & Treatment.        Edition: 12. McGraw-Hill Professional. 699-721
Hauser, C. Stephen., Darrell, S. Pardi., John, J. Poterucha., Mayo Clinic. (2004). Mayo Clinic             Gastroenterology and Hepatology Board Review. CRC Press. 195

Ko, H. Andrew., Malin, Dollinger, Ernest, H. Rosenbaum. (2008). Everyone’s Guide to Cancer Therapy: How Cancer Is Diagnosed, Treated, and Managed Day to Day. Andrews           McMeel Publishing. 586

Kune, S., Kune, G. A., & Watson, L. F. (1987). Case-control study of alcoholic beverages as      etiological factors: The Melbourne Colorectal Cancer Study Nutrition and Cancer     9(1):43-56

Lang,  S. Richard., Donald D. Hensrud, American Medical Association. (2004). Clinical            Preventive Medicine. 2nd Edition. AMA Bookstore. 52-52

Lee, D. & Marks, J.(2007). Colon Cancer. MedicineNet.com.             http://www.medicinenet.com/colon_cancer/article.htm]

Longnecker, M. P. (1992). Alcohol consumption in relation to risk of cancers of the breast and     large bowel. Alcohol Health & Research World .16(3)’:223-229.

Scheppach, Wolfgang.,  Bresalier, S. Robert., G. N. J. Tytgat. (2003). Gastrointestinal and Liver             Tumors. Springer.118-119

WCRF Food, Nutrition, Physical Activity and the Prevention of Cancer: a Global Perspective

Wells, G. Barbara. (2006). Pharmacotherapy Handbook. Edition 6. McGraw-Hill Professional. 622-630.

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