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Most colorectal cancers should be preventable, through increased surveillance, improved lifestyle, and, probably, the use of dietary chemopreventative agents.
Most colorectal cancers arise from adenomatous polyps. These lesions can be detected and removed during colonoscopy. Studies show this procedure would decrease by > 80% the risk of cancer death, provided it is started by the age of 50, and repeated every 5 or 10 years. As per current guidelines under National Comprehensive Cancer Network, in average risk individuals with negative family history of colon cancer and personal history negative for adenomas or inflammatory bowel diseases, flexible sigmoidoscopy every 5 years with fecal occult blood testing annually or double contrast barium enema are other options acceptable for screening rather than colonoscopy every 10 years (which is currently the gold standard of care).
Lifestyle and nutrition
The comparison of colorectal cancer incidence in various countries strongly suggests that sedentarity, overeating (i.e., high caloric intake), and perhaps a diet high in meat (red or processed) could increase the risk of colorectal cancer. In contrast, a healthy body weight, physical fitness, and good nutrition decreases cancer risk in general. Accordingly, lifestyle changes could decrease the risk of colorectal cancer as much as 60-80%. A high intake of dietary fiber (from eating fruits, vegetables, cereals, and other high fiber food products) has, until recently, been thought to reduce the risk of colorectal cancer and adenoma. In the largest study ever to examine this theory (88,757 subjects tracked over 16 years), it has been found that a fiber rich diet does not reduce the risk of colon cancer. A 2005 meta-analysis study further supports these findings. The Harvard School of Public Health states: "Health Effects of Eating Fiber: Long heralded as part of a healthy diet, fiber appears to reduce the risk of developing various conditions, including heart disease, diabetes, diverticular disease, and constipation. Despite what many people may think, however, fiber probably has little, if any effect on colon cancer risk."
More than 200 agents, including the above cited phytochemicals, and other food components like calcium or folic acid (a B vitamin), and NSAIDs like aspirin, are able to decrease carcinogenesis in pre-clinical development models: Some studies show full inhibition of carcinogen-induced tumours in the colon of rats. Other studies show strong inhibition of spontaneous intestinal polyps in mutated mice (Min mice). Chemoprevention clinical trials in human volunteers have shown smaller prevention, but few intervention studies have been completed today. The
However. this does not constitute sufficient evidence to recommend the general use of calcium supplements to prevent colorectal cancer. Aspirin chemoprophylaxis Aspirin should not be taken routinely to prevent colorectal cancer. Surgery remains the primary treatment. in people and in animals. it is less likely to be curable. ] Calcium The meta-analysis by the Cochrane Collaboration of randomized controlled trials published through 2002 concluded "Although the evidence from two RCTs suggests that calcium supplementation might contribute to a moderate degree to the prevention of colorectal adenomatous polyps. but "concluded that harms outweigh the benefits of aspirin and NSAID use for the prevention of colorectal cancer". which showed an inverse relationship with blood levels of 80 nmol/L or higher associated with a 72% risk reduction compared with lower than 50 nmol/L. it can be curable. while chemotherapy and/or radiotherapy may be recommended depending on the individual patient's staging and other medical factors. A second randomized controlled trial reported reduction in all cancers."chemoprevention database" shows the results of all published scientific studies of chemopreventive agents. When colorectal cancer is caught at early stages (with little spread). Subsequently. The Task Force acknowledged that aspirin may reduce the incidence of colorectal cancer. when it is detected at later stages (when distant metastases are present). A subsequent meta-analysis concluded "300 mg or more of aspirin a day for about 5 years is effective in primary prevention of colorectal cancer in randomised controlled trials. A clinical practice guideline of the U. . one randomized controlled trial by the Women's Health Initiative (WHI) reported negative results. long-term doses over 81 mg per day may increase bleeding events.". with a latency of about 10 years". Management The treatment depends on the stage of the cancer. Preventive Services Task Force (USPSTF) recommended against taking aspirin (grade D recommendation). A possible mechanism is inhibition of Hedgehog signal transduction. but had insufficient colorectal cancers for analysis. because the risk of bleeding and kidney failure from high dose aspirin (300 mg or more) outweigh the possible benefits. even in people with a family history of the disease. Vitamin D A scientific review undertaken by the National Cancer Institute found that vitamin D was beneficial in preventing colorectal cancer.S. However.
bypass.Because colon cancer primarily affects the elderly. including • • • wound infection. Most of these cases formerly subjected to "open and close" procedures are now diagnosed in advance and surgery avoided. any more procedures are thought by some to do more harm than good to the patient. Clinical trials suggest "otherwise fit" elderly patients fare well if they have adjuvant chemotherapy after surgery. • • Very early cancer that develops within a polyp can often be cured by removing the polyp (i. Curative surgical treatment can be offered if the tumor is localized. especially after surgery. If the tumor invaded into adjacent vital structures. colectomy). In colon cancer. palliative.e. anastomosis breakdown. In cases when anastomosis is not possible. so chronological age alone should not be a contraindication to aggressive management. the remaining parts of colon are anastomosed to create a functioning colon. a more advanced tumor typically requires surgical removal of the section of colon containing the tumor with sufficient margins. and/or peritonitis. .e. when surgeons find the tumor unresectable and the small bowel involved. bleeding with or without hematoma formation. Surgery Surgeries can be categorised into curative. fecal diversion. The worst case would be an "open-and-close" surgery. or open-and-close. and radical en-bloc resection of mesentery and lymph nodes to reduce local recurrence (i. As with any surgical procedure. Laparoscopic-assisted colectomy is a minimally invasive technique that can reduce the size of the incision and may reduce postoperative pain. palliative (noncurative) resection of the primary tumor is still offered to reduce further morbidity caused by tumor bleeding. If possible. invasion. colorectal surgery may result in complications. however. it can be a challenge to determine how aggressively to treat a particular patient. Surgical removal of isolated liver metastases is. which makes excision technically difficult. Curative surgery on rectal cancer includes total mesorectal excision (lower anterior resection) or abdominoperineal excision. polypectomy) at the time of colonoscopy. common and may be curative in selected patients. a stoma (artificial orifice) is created. This is uncommon with the advent of laparoscopy and better radiological imaging. • In case of multiple metastases.. the surgeons may prefer to bypass the tumor (ileotransverse bypass) or to do a proximal fecal diversion through a stoma. leading to abscess or fistula formation. dehiscence (bursting of wound) or hernia.. improved chemotherapy has increased the number of patients who are offered surgical removal of isolated liver metastases. and its catabolic effect.
and oxaliplatin (FOLFOX) with bevacizumab or infusional 5-fluorouracil. A 5-year study of patients who had surgery in 1997 found the risk of hospital readmission to be 15% after panproctocolectomy. or slow tumor growth. before surgery (neoadjuvant). ureters. most commonly to the small intestine. Chemotherapy is often applied after surgery (adjuvant). or as the primary therapy (palliative). chemotherapy after surgery is usually only given if the cancer has spread to the lymph nodes (Stage III). pneumonia. In colon cancer. arrythmia. leucovorin. folinic Acid) Irinotecan (Camptosar) Oxaliplatin (Eloxatin) Bevacizumab (Avastin) Cetuximab (Erbitux) Panitumumab (Vectibix) • In clinical trials for treated/untreated metastatic disease. and irinotecan (FOLFIRI) with bevacizumab or the same chemotherapy drug combinations with cetuximab in KRAS wild type tumors o o o o o o o o 5-fluorouracil (5-FU) or capecitabine UFT or Tegafur-uracil Leucovorin (LV. leucovorin. folinic Acid) Oxaliplatin (Eloxatin) • Chemotherapy for metastatic disease. The treatments listed here have been shown in clinical trials to improve survival and/or reduce mortality rate. and have been approved for use by the US Food and Drug Administration. spleen. .• adhesions resulting in bowel obstruction. and 11% after ileostomy adjacent organ injury. pulmonary embolism. shrink tumor size. Commonly used first line chemotherapy regimens involve the combination of infusional 5-fluorouracil. etc. 9% after total colectomy. or bladder. such as myocardial infarction. • • Chemotherapy Chemotherapy is used to reduce the likelihood of metastasis developing. • Adjuvant (after surgery) chemotherapy o 5-fluorouracil (5-FU) or capecitabine (Xeloda) o o Leucovorin (LV. and cardiorespiratory complications.
as it could lead to radiation enteritis. theoretical drug cost savings would be $753 million. director of oncology at the Lineberger Comprehensive Cancer Center at the University of North Carolina. and progressionfree and overall survival is increased.6% of all patients) would not receive cetuximab (other studies have found Kras mutation in up to 46% of patients).” cautions Goldberg.o o o o Bortezomib (Velcade) Oblimersen (Genasense.targeted at metastatic tumor deposits if they compress vital structures and/or cause pain . patients should now be tested for the KRAS gene mutation before being offered these EGFRinhibiting drugs. The mutation turns [EGFR] into a switch that’s always on. KRAS is a fail-safe. MD. the US Food and Drug Administration (FDA) updated the labels of two anti-EGFR monoclonal antibody drugs (panitumumab (Vectibix) and cetuximab (Erbitux)) indicated for treatment of metastatic colorectal cancer to include information about KRAS mutations.” says Richard Goldberg. The cost benefit of testing patients for the KRAS gene could potentially save about $740 million a year by not providing EGFR-inhibiting drugs to patients who would not benefit from the drugs. and it is difficult to target specific portions of the colon. since the rectum does not move as much as the colon and is thus easier to target. G3139) Gefitinib and erlotinib (Tarceva) Topotecan (Hycamtin) At the 2008 annual meeting of the American Society of Clinical Oncology. In July 2009." Radiation therapy Radiotherapy is not used routinely in colon cancer. “The trouble with the KRAS mutation is that it’s downstream of EGFR. "With the assumption that patients with mutated Kras (35. Following recommendations by ASCO. However. researchers announced that colorectal cancer patients that have a mutation in the KRAS gene do not respond to certain therapies. It is more common for radiation to be used in rectal cancer. having the normal KRAS version does not guarantee these drugs will benefit the patient. considering the cost of Kras testing. net savings would be $740 million.” But this doesn’t mean that having normal. you’re more likely to respond. “It doesn’t matter if you plug the socket if there’s a short downstream of the plug. or wild-type. “If you have wild-type KRAS. “It isn’t foolproof.” Tumors shrink in response to these drugs in up to 40 percent of patients with wild-type KRAS. Indications include: • Colon cancer o pain relief and palliation . those that inhibit the epidermal growth factor receptor (EGFR)--namely Erbitux (cetuximab) and Vectibix (panitumumab). but it’s not a guarantee.
Smaller lesions of the central or left liver lobe may sometimes be resected in anatomic "segments". intraoperative ultrasound. Treatment of lesions by smaller. Cancer Vaccine TroVax. to decrease the risk of recurrence following surgery or to allow for less invasive surgical approaches (such as a low anterior resection instead of an abdominoperineal resection). while large lesions of left hepatic lobe are resected by a procedure called hepatic trisegmentectomy. over 20% of patients present with metastatic (stage IV) colorectal cancer at the time of diagnosis. a cancer vaccine. Treatment of liver metastases According to the American Cancer Society statistics in 2006. if present. produced by Oxford BioMedica. and up to 25% of this group will have isolated liver metastasis that is potentially resectable.• Rectal cancer o neoadjuvant . and by direct palpation and visualization during resection. In locally advanced adenocarcinoma of middle and lower rectum. Resectability of a liver metastasis is determined using preoperative imaging studies (CT or MRI). Lesions confined to the right lobe are amenable to en bloc removal with a right hepatectomy (liver resection) surgery.given before surgery in patients with tumors that extend outside the rectum or have spread to regional lymph nodes.where a tumor perforates the rectum or involves regional lymph nodes (AJCC T3 or T4 tumors or Duke's B or C tumors) palliative . Some lesions which are not initially amenable to surgical resection may become candidates if they have significant responses to preoperative chemotherapy or immunotherapy regimens.to decrease the tumor burden to relieve or prevent symptoms o Sometimes chemotherapy agents are used to increase the effectiveness of radiation by sensitizing tumor cells. Lesions which are not amenable to surgical resection . nonanatomic "wedge" resections is associated with higher recurrence rates. Immunotherapy Bacillus Calmette-Guérin (BCG) is being investigated as an adjuvant mixed with autologous tumor cells in immunotherapy for colorectal cancer. Lesions which undergo curative resection have demonstrated 5-year survival outcomes now exceeding 50%. • o adjuvant . and phase III trials are planned for colon cancers. regional hyperthermia added to chemoradiotherapy achieved good results in terms of rate of sphincter-sparing surgery. is in Phase III trials for renal cancers.
while those with distant metastases (any T. These services help to mitigate some of the difficulties of integrating patients' medical complications into other parts of their lives. including a prospective cohort of 1. and inhibits tumor growth and metastases in animal models. through several mechanisms . For example. Those with a more invasive tumor. Several reports. cryoablation. and other services. any N. as they are typically quite advanced.for cure can be treated with modalities including radio-frequency ablation (RFA). yet without node involvement (T3-4. N0. Patients with positive regional lymph nodes (any T. Support therapies Cancer diagnosis very often results in an enormous change in the patient's psychological wellbeing. . Prognosis Survival is directly related to detection and the type of cancer involved. Various support resources are available from hospitals and other agencies. social service support. and the comfort of the surgery performing potentially complex hepatic surgery. N1-3. M0) have an average 5-year survival of approximately 40%. Cimetidine Cimetidine is being investigated in Japan as an adjuvant for adenocarcinomas. and chemoembolization. Survival rates for early stage detection is about 5 times that of late stage cancers. M0) have an average 5-year survival of approximately 90%. The influence of aspirin on survival after diagnosis of colorectal cancer is unknown. Patients with colon cancer and metastatic disease to the liver may be treated in either a single surgery or in staged surgeries (with the colon tumor traditionally removed first) depending upon the fitness of the patient for prolonged surgery. which provide counseling. but overall is poor for symptomatic cancers. cancer support groups.279 people diagnosed with stages I-III (nonmetastatic) colorectal cancer. N0. Multiple small trials suggest a significant survival improvement in the subset of patients with the sLeX and sLeA biomarkers that take cimetidine treatment perioperatively. patients with a tumor that has not breached the muscularis mucosa (TNM stage T1-2. M1) have an average 5-year survival of approximately 5%. Aspirin A study published in 2009 found that aspirin reduces risk of colorectal neoplasia in randomized trials. M0) have an average 5-year survival of approximately 70%. the difficulty expected with the procedure with either the colon or liver resection. including for stage III and stage IV colorectal cancers biomarked with overexpressed sialyl Lewis X and A epitopes.  have suggested a significant improvement in cancer-specific survival in a subset of patients using aspirin.
For other abnormalities. patients who had poorly differentiated tumors or venous or lymphatic invasion) and are candidates for curative surgery (with the aim to cure). except if it could not be done during the initial staging because of an obstructing mass. References 1. a polyp >1 centimeter or high grade dysplasia is found.gov/cancertopics/commoncancers. If a villous polyp. Routine PET or ultrasound scanning. but did not originate from the original cancer (metachronous lesions). H&E stain. chest X-rays. ^ "Cancer". The U. February 2006. any metastasis or tumors that develop later. A medical history and physical examination are recommended every 3 to 6 months for 2 years. ^ "Cancer".CEA level is also directly related to the prognosis of disease.cancer. The aims of follow-up are to diagnose. in the earliest possible stage. Follow-up Micrograph of a colorectal villous adenoma. . the colonoscopy can be repeated after 1 year. abdomen and pelvis can be considered annually for the first 3 years for patients who are at high risk of recurrence (for example. then every 5 years. A CT-scan of the chest.S.who. National Comprehensive Cancer Network and American Society of Clinical Oncology provide guidelines for the follow-up of colon cancer. World Health Organization. Retrieved 24 May 2007. A colonoscopy can be done after 1 year. then every 6 months for 5 years. http://www. http://www. 2009. complete blood count or liver function tests are not recommended. These lesions are considered pre-cancerous.int/mediacentre/factsheets/fs297/en/. These guidelines are based on recent meta-analyses showing intensive surveillance and close follow-up can reduce the 5-year mortality rate from 37% to 30%. 2. but are only advised for patients with T2 or greater lesions who are candidates for intervention. since its level correlates with the bulk of tumor tissue. Carcinoembryonic antigen blood level measurements follow the same timing. National Cancer Institute. in which case it should be performed after 3 to 6 months. it can be repeated after 3 years.
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