Treatment of Colorectal Cancer - Case Study Example

Approach To Colorectal Cancer Introduction Colorectal cancer is the second most common cancer and the second leading cause of cancer death in the United States. [1] The incidence and mortality of colorectal cancer increase with age, especially after 60 years of age. Worldwide, the mortality from this disease is estimated to have been 500, 000. [2] As with many other cancers, the development of colorectal cancer results from interaction between genetic and environmental influences. As many as 25% of patients with colorectal cancer have a family history of the disease, which suggest the involvement of a genetic factor.[3] Familial Adenomatous Polyposis (FAP), Hereditary Nonpolyposis colorectal cancer(HNPCC) and long standing Inflammatory Bowel Disease are associated with increased risk of developing colorectal cancer. Dietary factors may increase or decrease risk of colorectal cancer, e.g. a review of the data concerning saturated fat concluded that diets high in fat possibly increased the risk of colorectal cancer but the evidence relating risk to intake of monounsaturated fat and polyunsaturated fat was inconsistent.[4]High fat intake has also been found to increase the risk of adenoma recurrence after polypectomy.[5]Smoking and decreased physical activity have been associated with increased risk of colorectal cancer.[6][7] In the other hand fresh fruit and leafy green vegetables reduce the risk of colorectal cancer.[8] Treatment of colorectal cancer is essentially surgical. According to staging of cancer radiotherapy is used before and after surgery in stage 11 and stage 111 of rectal cancer. It can be used also in combination with chemotherapy postoperatively. [2] Complementary therapy can produce good help to colorectal cancer patients. Pathogeneses Adenomas Most colorectal cancers arise from pre-existing adenomas. These premalignant lesions should be distinguished from juvenile polyps, hamartomas, and inflammatory polyps, which are not proved to progress to colorectal cancer. Adenomatous polyps are grossly visible. They are classified histologically into tubular type, villous type and tubulovillous. Villous polyps are more likely to contain invasive carcinoma than are tubular polyps. Regardless of the histological type, large adenomas, more than one cm in diameter, are more liable to contain invasive carcinoma. [2] Evidence suggesting that colorectal cancer arises from premalignant adenomatous polyps: 1. Prevalence of colorectal cancer in countries with high incidence of adenomatous polyps. 2. Patients with previous history of resection of Adenomatous polyps are at high risk of developing colorectal cancer. 3. Adenomas are detected in younger patients while cancer s present mostly in old patients that is adenomas are precursor of cancer. 4. Colorectal cancer and adenomas are both of genetic alteration origin. 5. Early resection of adenomas by colonoscopy reduces the incidence of colorectal cancer. [2 ] Genetic Alteration The successive evolution of normal colonic mucosa to a benign adenoma, then to an Adenomatous polyp containing cancer, then to potentially life-threatening invasive cancer is associated with a series of genetic events occurring over a long period. The original model that was proposed over years ago involves key derangements in several genes, including APC (in patients with familial adenomatous Polyposis), K-ras, DCC, and p53. APC gene mutations alter cell adhesion; they also affect the WnT signaling pathway. C-myc, a transcription factor, is activated by abnormal WnT signaling, skewing the balance between proliferation and aptoptosis. Loss of APC influences tumor initiation, where as inactivation of E-cadherin, which complexes with beta catenin, plays a role in tumor progression. [2] Familial Adenomatous Polyposis (FAP) FAP is an autosomal dominant disorder characterized by the presence of numerous Adenomatous polyps, each less than one cm in diameter, all over the wall of the large bowel.This familial disorder is associated with extracolonic lesions, like osteomas, desmoids tumors, epidermoid and sebaceous cystsmpigmented retinal lesions, upper gastrointestinal tract polyps, and perampullary cancers or brain tumors. [3] Polyps developed during second and third decades of life. If surgery not done, colorectal cancer mostly develop by 40 years of age. Genetic testing is now the standard of care for FAP. Despite the detailed genetic knowledge of FAP that is now available, genetic testing is often poorly interpreted. So, genetic counseling is an integral part of management and should precede genetic testing. [9] Testing for FAP in a family is most informative when it begins with the affected family member, to identify the mutation responsible for FAP within that family. Once a causal mutation has been identified in an affected person, predictive testing can be done to identify other family members at risk. [10] Surgical prophylaxis in FAP includes resection of the whole large intestine, to prevent malignant transformation. Hereditary Nonpolyposis Colorectal Cancer It is an autosomal dominant disorder like FAP. In contrast to FAP it is associated with unusual high frequency of cancers in the proximal large bowel. If HNPCC is diagnosed, affected family members should undergo colonoscopy between the age of 20 and 25 or at the age of 10 years younger than the youngest age at diagnosis in the family, whichever is earlier, to be repeated every 1 to 2 years. [11] If an adenoma or adenocarcinomas of the colon is detected, total colectomy with an ileorectal anastomoses is done. In women, total abdominal hysterectomy and bilateral salpingo-oophorectomy are considered, especially if the patient has no intention of having children later, because of the increased risk of ovarian and endometrial carcinoma. [12] Inflammatory Bowel Disease: Long standing, extensive inflammatory bowel disease, including ulcerative colitis and Crohn colitis increases the risk of colon cancer. Colonoscopy with multiple biopsies of the entire colon should be done every 1 to 2 years after 8 years disease in patients with pancolitis or after 15 years in those with left –sided colitis. According to the results of biopsies colectomy must be carefully considered. [12] Environmental Factors Specific factors increase the risk of colorectal cancer, while others reduce risk, shown in the table. [2] Risk Rate Age 50 years and older Decreased risk High vegetable consumption Oral contraceptive use Estrogen replacement Multivitamins containing folic acid Long term use of aspirin and non- steroidal Increased risk Family history and familial adenomas Long standing Inflammatory bowel disease Physical activity (> 3 hr of exercise/week) Obesity Smoking Alcohol(< 1 drink/day Note: Table is modified Diagnosis Clinical Manifestations Usually patient seeks medical advice when passing blood with stool but this may be late. Before noticing blood the patient may complaint of symptoms suggesting anaemia like fatigue, pallor, bone-ache and palpitations. Bleeding per rectum maybe intermittent, so test for fecal occult blood may not be positive. Cancer in the rectosigmoid colon is associated with tenesmus, narrowing of the stool, and streaks of blood with stool. Patient and general practitioners may attribute these manifestations to haemorrhoids. Per rectal digital examination and colonoscopy should be done in this condition. Investigations Fecal Occult Blood Testing (FOBT) Large adenomas and most cancers bleed, so patients and high risk people (with positive family history and old age) should be screened by testing the presence of fecal occult blood. Meta-analysis of mortality results from randomized, controlled trials shows that patients screened with FOBTs had a decrease in colorectal mortality of 16%. When adjusted for screening attendance in individual studies, the mortality reduction is 23%. [13] The sensitivity of FOBT has ranged from 25% to over 90%. The disadvantage of low sensitivity is that you may reassure patient with false negative test. Also high false positive rate may result in persons, free of cancer, undergoing follow up colonoscopy, with its associated risks and costs. Data from the Minnesota trial suggest that screening process would result in 2,800 participants having at least one colonoscopy, with 3.4 colonoscopy complications (perforation or haemorrhage). [13] Two types of FOBTs are available: chemical tests and immunochemical tests. Chemical tests are subject to false positive results caused by dietary substances or drugs. The sensitivity of immunochemical test is better than the chemical test, without an unacceptable decline in specificity. [14]. the immunochemical test characterized by being not affected by diet or drugs. Flexible Sigmoidoscopy It an important diagnostic and screening tool in detecting cases of colorectal cancer. A prospective study showed that screening (primarily with flexible sigmoidoscopy) was associated with a 60% reduction in the incidence of distal colorectal cancer. [15]In the United Kingdom, the baseline findings of a multicenter trial showed that of 40,000 patients screened , distal adenomas were detected in 12%, and distal cancers were detected in 0.3%.[16] Restrictions of widespread use of flexible sigmoidoscopy include lack of training and low reimbursement rates. Training of nonphysicians to perform flexible sigmoidoscopy may facilitate more widespread use of this procedure, particularly in high-volume centers. Colonoscopy The effectiveness colonoscopy has been demonstrated by several studies. In a study of 3,212 United States veterans (almost all men) with a mean age of 63 years, an adenoma incidence rate of 37% was reported. The incidence of advanced adenoma (more than 10 mm in diameter, villous features, and high-grade dysplasia or cancer) was 10.5%. [17] A study in 1,322 women reported an adenoma incidence of 21% and an advanced adenoma incidence of 3%. The study showed that colonoscopic polypectomy lower the incidence of colorectal cancers by 90%. [18] Double Contrast Barium Enema (DCBE) A comparison study in patients who have undergone colonoscopic polypectomy found colonoscopy to be more effective method of surveillance than DCBE. [19] Prognosis The prognosis for the patients with colorectal adenocarcinomas closely related to the depth of tumor penetration into the wall of the bowel and the presence or absence of regional lymph node involvement and distant metastases, i.e. tumor cells invaded other organs as the lung, liver, bone, or other anatomically distant sites. Stages Stage A: It describes superficial lesions which do not penetrate the muscularis layer of the wall of the colon and do not involve regional lymph nodes. Stage B: It describes lesions that penetrate deeply into the wall of the bowel including the muscularis layer without involving regional lymph nodes. Stage C: Tumors with regional lymph nodes involvement. Stage D: Tumor cells have metastasized liver, lung, bone, or other distant sites. This stage has the worse prognosis. Prognostic Tool Carcinoembryonic Antigen (CEA) is an imperfect tumor maker but there are several defined roles for the CEA assay: 1. Preoperatively, the CEA level is related to the stage disease and may serve as a predictor of surgical incurability: preoperative CEA values greater than 5ng/ml have been associated with poor prognosis, independent of surgical stage.[19] 2. Postoperatively, the CEA level may serve as a measure of the completeness of tumor resection. If a preoperatively elevated CEA values does not fall to normal levels within 4 weeks (a period that is twice the plasma half-life of CEA) after surgery, the resection was probably incomplete or hidden metastases are present. 3. The CEA level may serve as a useful monitor for recurrent cases. 4. The CEA level may serve as a monitor of response to chemotherapeutic treatment of metastatic tumors. Until better reagents become available, the CEA assay will remain a source of information about tumor status that is unavailable by other means. Thus, this assay continues to merit a role in the management of selected colorectal cancer cases. [2] Treatment Surgical Management Surgical resection of the tumor gives the greatest chance for cure of patients suffering from colorectal cancer. Regarding the often old age of the patients, they should be thoroughly evaluated before surgery, especially for detection of metastases. Preoperative Evaluation Patients should be physically examined, X-Ray of the chest, to check for lung metastases, C.T. Scan to detect liver metastases or lymph nodes involvement, and X-Ray for skeletal bones, to exclude bone metastases. CEA level is measured to predict surgical outcome. Symptoms of anorexia, loss of weight and fever may point to hepatic metastases. Preoperative Trans Rectal Ultrasonography (TRUS) is very helpful in cases of distal rectal tumors as it visualizes the degree of tumor penetration into the layers of the rectum. The procedure has an accuracy of82% to 93% with respect depth of invasion. Assessment lymph node involvement is less reliable, with reported accuracy of 65% to 81%. [2] Procedure Affected segment of the colon should be resected together with 5cm safety margin of both sides, draining regional lymph nodes, and associated blood vessels. Tumors in the distal rectum are problematic. The surgeon should do his best to preserve the anal sphincter. In cases of rectal tumors 5 to 6 cm close to the anal verge, abdominal-perineal resection is done with permanent sigmoid colostomy. However staple devices permit the construction of end-to-en anastomoses by experienced surgical oncologists for many patients with midrectal tumors. The ideal margin for rectal cancer resection is 2 cm or more distally and 5 cm or more proximally. Lymphovascular resection of the rectum should include a wide anatomic resection of the mesorectum. [20] Minimally invasive (laparoscopic) colectomy is still not settled, but probably it will be used widely in the near future. Laparoscopic resection of rectal cancer is even more challenging and is being perfected in specialized centers. [2] Postoperative Follow Up If preoperative colonoscopy was normal (no colonic adenomas detected) subsequent colonoscopy should be done 3 years after surgery and if the outcome was normal, it can be done every 5 years. The intent is to detect recurrent adenomatous polyps and new primary cancers. [21] Flexible Proctosigmoidoscopy. Surveillance with flexible proctosigmoidescopy is appropriate for selected patients with rectal cancer. Combined chemotherapy and pelvic radiation represent the standard approach for stages B and C rectal cancer. For patients who have not received pelvic radiation, direct visualization of the rectum at periodic intervals is suggested. [2] Radiation Therapy Radiotherapy plays an important role in the treatment of patients with stage B or stage C rectal tumors. Cancer recurs locally or regionally in 20% to 40% of these patients after complete resection. This unusually high recurrence is the result, presumably, of two factors: loss of integrity of the serosa of the colon, as it enters the pelvis, facilitates the infiltration of the tumor, and the rich lymphatic supply of the side pelvic wall adjacent to the rectum, enhances the early spread of the malignant cells into surgically inaccessible sites. So, adjuvant radiotherapy was introduced to remove malignant cells from perirectal tissues and to increase chance of cure. [22] Radiotherapy has been used to treat cancer for more than 100 years. Most radiotherapy uses high-energy X-rays that are produced by a machine called a Linear Accelerator. This X-rays have about 500 to 1,000 times more energy than the ordinary X-rays used for imaging. This high energy means that the X-rays can go deeper into tissues and destroy malignant cells. [23] Advantages of Radiotherapy 1. When used before surgery it produces shrinkage of the tumor size which facilitates surgical resection. 2. It may lower the recurrence rate. 3. It increases the 5 year survival rate by 16%.[24] 4. When combined with chemotherapy .survival is prolonged. [ 2 ] Disadvantages (side effects) a. Acute or short-term side effects, last for few weeks 1. Diarrhoea 2. Tiredness 3. Sickness 4. Pain in the lower abdomen: This happens to about 6% of patients and lasts up to 6 months for 1% of them. This complaint probably is caused by nerve damage. [25] 5. Wound infection: About 20% of patients who received radiotherapy had wound infection after surgery, compared with 10% of those who did only surgery. [25] 6. Blood loss intraoperatively is more in patients who had preoperative radiotherapy, than in patients who had only surgery. [26] b. Long-Term Side Effects 1. Blood clots in legs or lungs: About 1 in 13 patients who have radio- therapy get blood clots. Usually these clots do not cause problems. [25] 2. Bowel blockage: This means some patients could not pass stool, so emergency surgery may be needed to clear the blockage. [25] 3. Tenesmus: It is sensation of urge to pass stool. This symptom may interfere with social life of the patients. 4. Sexual problems: If radiotherapy caused damage of pelvic nerves patients may experience erectile dysfunction or ejaculation problems. Women may get dry vagina. Chemotherapy This treatment modality is very important in treatment of advanced colon cancer. Some new drugs have been emerged but 5- fluorouracil is still a basic for most regimens. Fluorouracil 5-Fluorouracil, synthesized in 1952, is given as a bolus injection weekly or daily for 5 days every 4 weeks. Partial response rates with these regimens have been ranged from 10% to 15%. Development of portable infusion pumps permits the continuous infusion of 5-flourouracil on an outpatient basis. Continuous infusion increases the efficacy of the drug. The use of 5-Fu with leucovorin results in a higher response rate than with 5-FU alone. [2] Capecitabine Capecitabine is a prodrug of 5-flourouracil that mimics continuous –infusion 5-FU. It has the advantage of oral administration. Ii two studies that compared capecitabine with 5-FU in patients with advanced cancer, capecitabine therapy was associated with an improved response rate (26% versus 17%), but there was not a significant benefit in survival.[27] Irinotecan Irinotecan is a new topoisomerase inhibitor that has significant therapeutic activity in metastatic colorectal cancer. It is used in cases of tumor recurrence or spread after primary chemotherapy. Disadvantage of this drug: Diarrhoea and neutropenia, which can be life threatening if not treated promptly and aggressively. Oxaliplatin It is also used in treatment of colorectal cancer. It causes no renal toxicity and minimal hematological toxicity, but it is associated with reversible, acute, cold-related dysesthesia and a dose-limiting, cumulative, peripheral sensory neuropathy. [2] Combined Therapy Use of radiotherapy together with chemotherapy decreases the possibility of local or regional recurrences after complete resection of stage B or stage C rectal cancer and prolong survival. The chemotherapy causes radiosensetization so makes it more effective. This approach produced its most successful outcome when a continuous infusion of 5-FU was administered through a portable pump for the entire 4- to 5-week period of radiation therapy. [2] Palliative Therapy: Stenting of obstructing rectosigmoid or rectal cancers as well as use of laser photoablation should be considered if surgical decompression is not possible or advisable due to presence of extensive metastatic disease or comorbidity. [2] Complementary therapy: Many patients with cancer use complementary therapies to help support themselves through cancer and its treatment. It may be bewildering to spend time in hospitals, which can seem frightening and impersonal, and to meet so many different health professionals, as well as coping with the high-tech machinery and techniques used in cancer treatment. At the same time it can be difficult to cope with the implications of the illness itself. [28] Complementary therapists usually with the person as a whole, not just the part of the body with the cancer. This is called a holistic approach and is sometimes good medical practitioners also do. A complementary therapist who listens and cares may help patient to cope with some of those difficult feelings, which can be an effective way of getting back some control. Some hospitals provide complementary therapies as a part of cancer care, together with conventional cancer treatment, such as chemotherapy or radiotherapy. Advantages of complementary therapy: It can help patients feel better and improve their quality of life It improves general heath of patients It gives patients a sense of control over what is happening to them It reduces stress, tension, sleeplessness, anxiety, depression and makes patients feel more relaxed. It helps to reduce the symptoms of cancer, such as pain, feeling sick, breathlessness, constipation, diarrhoea, tiredness and poor appetite It helps to reduce some of the side effects of cancer treatment Patients claim that complementary therapy does a better job than conventional medicine of meeting their emotional needs and respecting their religious and cultural beliefs. [29] Disadvantages: There may be complementary therapies that are not suitable for some types of cancers or during a particular treatment. It is important to inform the professional staff in the hospital about the type of complementary therapy the patient, with cancer, has. In the other hand the complementary therapist should know that the patient has cancer. [28] Complementary medicines should be evaluated as rigorously as conventional medicine to protect public from charlatans and unsafe practices, but many practitioners of CAM are reticent about evaluation of their practice. Skeptics maintain that this is because of fear that investigations will find treatment in effective and threaten livelihoods. [30] Types of therapies [28] Relaxation: Simple breathing and relaxation exercises are very useful in reducing anxiety and stress and reducing the harmful effects of stress on the body Relaxation exercise Visualisation (mental imagery): This is a technique that involves creating images in the patient mind while he is in a state of relaxation (e.g. imagine that you are lying in a field full of beautiful flowers) Hypnotherapy (hypnosis): It helps patients in reducing some side effects associated with chemotherapy and radiotherapy such as nausea and vomiting. In this method, the hypnotherapist leads the patient into deeply relaxed state, during which the patient is still conscious of the surrounding Art therapy: This therapy help patients to express themselves through working with materials by communicating feelings such as fear or anger through painting, drawing or sculpting. Healing: Healers believe that healing energy exists all around us, and they act as channel through which healing energy flows into patient. Reiki: It is a method somewhat like relaxation method with moving the hands all over the body in certain sequences according to the therapist instructions Medition: It is a way of working with the mind. It uses mental exercises which can help to deeply relax and calm the mind. [28] Herbs and Dietary supplements Some biologics and micronutrients have been found as having the potential to prevent induction and inhibit the development of preinvasive and invasive neoplasia and its progression. Increasing evidence from animal research, observational human studies, and clinical trials, suggests that some nutrients may indeed help prevent certain cancers or assist in cancer therapies. [31] The concept of cancer prevention using nutrients is based on evidence from human epidemulogy, clinical trials, and studies of animal carcinogenesis models for cancer-inhibiting potential of these nutrients and non-nutrients derived from food. Basic research has identified nutrients as agents that are carcinogen-blocking, are antioxidants/anti-inflammatory, and are capable of inhibiting mutagenesis and hyperproliferation, as well as that induce apoptosis or differentiation as critical characteristics for chemoprevention regardless of their molecular targets. More than 40 diet-derived agents and agent combinations have been evaluated clinically as chemopreventive agents for major cancer targets, including breast, prostate, colon, and lung cancers. Some of the most promising nutrients identified as chemopreventive agents include soy isoflavones, green and black tea polyphenols, curcumin, lycopene, indole-3-carbinol, vitamin D, folic acid, and E, selenium, and calcium. [32] Conclusion Biomedical treatment is essential in treatment of cancer and cannot be replaced by complementary medicines. However complementary remedies can be used together with conventional procedures for the benefit of the patient as these natural approaches give the patient better feeling of their inner power in front of their serious illness. More over these remedies serve improved quality of life and make the side effects of the biomedical treatments less. Combination of both types of treatments arises the chance of widening the scope of health care beyond the domain of biomedicine, targeting the improvement outcome of the patient as a whole. Conclusive evidence of the importance of CAM therapies can be obtained only from well-characterized agents tested in suitable cohorts and using the same scientific rigor used to evaluate pharmaceutical agents and also using reliable intermediate biomarkers of cancer for evaluating their efficacy. [31] By subjecting the practitioners to high education and qualified training, together with opened communications with medical professionals and more co-operations between them in favor of patients, the healthcare system will be more efficient in providing safe, high quality, and effective treatments. References 1. Jemal A, et al: Cancer Statistics, 2003. CA Cancer J Clin 53:5, 2003 2. Bernard Levin: Colorectal Cancer.2005, retrieved by Medscape. 3. Rustgi AK: Hereditary gastrointestinal Polyposis and Nonpolyposis syndromes. N Engl J Med 331: 1694,1994 4. Colon and Rectum. Food, Nutrition and the Prevention of Cancer: A Global Perspective. 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Use of complementary/integrative nutritional therapies during cancer treatment: Implications in clinical practice. Cancer Control. 2002; 9(3): 236-243. 32. Kumar B, Besterman-Dahan K. Nutrients in chemoprevention of prostate cancer: current and future prospects. Cancer Control. 1999; 6: 580-586. Read More