Survey
* Your assessment is very important for improving the workof artificial intelligence, which forms the content of this project
* Your assessment is very important for improving the workof artificial intelligence, which forms the content of this project
MINISTRY OF HEALTH OF UKRAINE VINNITSA NATIONAL PIROGOV MEMORIAL MEDICAL UNIVERSITY "CONFIRM" at the methodical meeting Department of Ray diagnostics, Ray therapy and Oncology Head of the department As. of Prof., M.S.D. Kostyuk A.G. ________________________ "______" ________ 2013 year METHODICAL GUIDELINES For self-study for students in preparing for the practical (seminary) lessons Subject of Study Oncology Module No 1 Theme No 7 Topic of Lesson Colon cancer. Risk factors. Classification by TNM. Methods of diagnostics. Clinics. Treatment: surgery, radiotherapy, chemotherapy, combined. Course 5 Faculty General Medicine 2 Topicality. Colorectal cancer is the third most common malignant tumor and the fourth most common cause of cancer death in the world. Every year it was estimated that worldwide there would be 945,000 new colorectal cancer cases and 492,400 colorectal cancer-related deaths. In the United States every year are expected 106,680 new cases of colon cancer (men 49,220; women 57,460), and 42,000 new cases of rectal cancer (men 23,580; women 18,350). Colorectal cancer is the second leading cause of cancer related death in the United States with 68,000 deaths annually representing 10% of all cancer deaths. Age is a major risk factor in developing colon cancer. Increase the risk of developing colorectal cancer is approximately after age 50. Learning Objectives: 1 Incidence and epidemiology 2. Etiology and Risk factors. 3. Differential diagnosis between benign tumors and Colon cancer. 4. The ways of spreading Colon cancer. 5. Classification TNM. Stages of Colon cancer. 6. Hystologic Classification Colon tumors. 7. Main symptoms in dependent of localization. 8. Treatment tactics 9. Surgical treatment of Colon cancer in dependent of localization 10. Choice the method of treatment (surgical, chemo- and radiotherapy). 11. Indications and contraindications for chemo- and radiotherapy. 12. Survival and prognosis. 13. Palliative care Colorectal Cancer Statistics In the United States, 106,680 new cases of colon cancer were expected in 2006 (men 49,220; women 57,460) (1), and 41,930 new cases of rectal cancer were expected in 2006 (men 23,580; women 18,350). Colorectal cancer is the second leading cause of cancer related death in the United States with 68,000 deaths annually representing 10% of all cancer deaths. Age is a major risk factor in developing colon cancer. The lifetime risk of developing colorectal cancer is approximately 5% with the vast 3 majority of cancers occurring after age 50. The overall incidence has been falling perhaps due to screening. Epidemiologic Associations The vast majority of colorectal cancers are sporadic and not familial. Epidemiologic studies demonstrate an increased risk of colorectal cancer with the following conditions/characteristics: • Family history of colorectal cancer is associated with an increased risk ofdeveloping colorectal cancer. If one first-degree family member had colorectal cancer, the risk increases 1.7-fold • Western/urbanized societies • Diet high in red or processed meat • Increased bowel anaerobic flora • Diabetes mellitus/insulin resistance: the risk of colon cancer may be 30% higher in diabetics compared with nondiabetics • Inflammatory bowel disease. Increased incidence is seen with both Crohn’s disease and ulcerative colitis and is associated with the severity, extent, and duration of disease affecting the colon. The risk of colon cancer in ulcerative colitis is approximately 10% at 10 year duration, 20% at 20 year duration, and >35% at 30 year duration. Total colectomy eliminates the risk of colon cancer. • Cigarette smoking • Alcohol consumption • Ureterosigmoidostomy • Streptococcus bovis bacteremia • Prior pelvic radiation RISK FACTORS DIETARY A typical Western diet consists of increased intake of fats and red meats, and decreased fruit and vegetable intake. Epidemiologic studies suggest a relationship between lifestyle, diet, and colorectal cancer risk. Modifying dietary and lifestyle factors could help in the prevention of colorectal cancer as well as provide other health benefits. ALCOHOL AND TOBACCO Daily alcohol consumption increases the risk of colon cancer. There is a twofold increase in risk of colon cancer in individuals who consume greater than two drinks per day. Beer intake has been suggested to increase risk of CRC, mainly of rectal cancer PHYSICAL ACTIVITY AND TOTAL BODY MASS 4 There is a definite relationship between physical activity and decreased colon cancer risk, but not rectal cancer risk. NONSTEROIDAL ANTIINFLAMMATORY DRUGS Nonsteroidal antiinflammatory drug (NSAID) use is associated with a decreased risk of colorectal cancer. The majority of the epidemiologic studies in the literature reveal that there is a decrease in adenoma incidence, carcinoma incidence, and colorectal cancer mortality associated with NSAID use. The use of aspirin for at least 16 days per month reportedly reduces colorectal cancer risk by 50% and reduces the risk of colorectal cancer death by 40%. Age The incidence of colorectal cancer increases after age 50 years. In the Surveillance, Epidemiology and End Results statistics for the period 1995 to 1999, the incidence rate of colorectal cancer was 48 per 100,000 population for individuals between 40 and 49 years of age, while it was 327 per 100,000 population for individuals aged 60 to 69 years. The incidence rate increased with each subsequent decade age. Prior History of Adenomas A personal history of adenomas will increase the risk of subsequent adenomas and thus of colorectal cancer. Family History of CRC and Adenomas Family history of colorectal cancer in a firstdegree relative increases the risk of colorectal cancer two- to threefold Prior History of Colorectal Cancer After curative resection, patients with colorectal cancer are at risk of recurrent disease. However, the main purpose of endoscopic surveillance is to detect metachronous lesions. The incidence of metachronous colorectal cancer and adenomas in patients with a personal history of CRC is approximately 6% and 25%, respectively. Hereditary Nonpolyposis Colorectal Cancer HNPCC is an autosomal dominant syndrome characterized by early age onset of colorectal cancer, right-sided predominance, excess synchronous and metachronous colorectal neoplasms, and extracolonic malignancies such as endometrial cancer, small-bowel cancer, renal, pelvis, and ureter cancers, and skin lesions such as sebaceous adenomas, keratoacanthomas, and sebaceous carcinoma. The median age of onset of CRC is 45 years. Hamartomatous Polyposis Syndromes Peutz-Jeghers and juvenile polyposis are the most common hamartomatous polyposis syndromes predisposing to colorectal cancer. Peutz-Jeghers patients are also at risk of stomach, pancreas, breast, and uterine carcinoma, as well as ovarian sex cord tumors. In addition to colorectal cancer, juvenile polyposis patients are at risk of 5 gastric, duodenal, and pancreatic cancers. In both of these syndromes, there are no evidence-based surveillance recommendations. The recommendations have to be individualized. Genetic testing is also available for affected patients. Crohn Disease The incidence and characteristics of colorectal cancer in Crohn disease have been reported to be similar to ulcerative colitis. There are no specific recommendations for surveillance in Crohn disease. However, following the model of ulcerative colitis, recommendations can be made for colonoscopy after 8 years of diagnosis and then every 1 to 2 years. Consideration should be given to random biopsies every 10 cm. Ulcerative Colitis In a meta-analysis of 116 publications in the English language, was noted that the annual colonoscopy should be performed after 8 years of pancolitis. If the disease is confined to the left side of the colon, then surveillance can be started at a later time. It is imperative to perform random biopsies every 10 cm. If there is severe dysplasia in the specimens, consideration should be given to surgery, as there is a high incidence of occult cancer in the colon. Development of Colorectal Cancer from Polyps Most colorectal cancers arise from adenomatous polyps. The progression of adenomatous polyps from small polyps, to larger polyps, to dyspastic polyps, and finally to cancer occurs over at least a 10 year period. Colonoscopy is best method allows for direct visualization of the colon and, if necessary, polypectomy. Approximately 3–6% of Americans undergoing colonoscopic screening in their 50s will have a colon cancer, dysplastic polyp, or villous adenoma. For patients without a family history of colon cancer, the United States Multisociety Task Force recommends screening patients beginning at age 50 with annual fecal occult blood test as well as sigmoidoscopy every 5 years. For patients with two or more affected first-degree relatives or any firstdegree relative with colon cancer under the age of 60, screening should begin by age 40 or at least 10 years younger than the age at which the affected family member was diagnosed. Pathology of Primary Tumors Approximately 95% of the malignant colorectal tumors are adenocarcinomas. Macroscopically, colorectal tumors can be described as ulcerative, polypoid, or infiltrative. Histopathologically, colorectal adenocarcinomas are classified as well, moderately, or poorly differentiated, depending on the formation of glandular elements. Well and moderately differentiated adenocarcinomas have more glandular components than do poorly differentiated tumors. 6 Adenocarcinomas of the colon and rectum are also described depending on additional cytological and histopathologic characteristics. Mucin-producing tumors characterized by extracellular mucin pools. Signet-ringcell–type adenocarcinomas characteristically have intracellular mucin pushing the nuclei to give the cell the characteristic signet ring appearance. Adenosquamous carcinomas are composed of both glandular and squamous elements. PRESENTATION AND STAGING Signs and Symptoms The presenting symptoms depend on the location of the tumor. Obstruction, perforation, change in stool character, and hematochezia are more common with leftsided tumors. Anaemia is more common features right-sided tumors related. The most common symptoms of large bowel cancer are a change in bowel habits (constipation or diarrhoea or sometimes alternating constipation and diarrhoea), bleeding from the bowel, and a feeling of incomplete evacuation after going to the toilet. In some cases patients are not aware of any symptoms until the cancer has caused partial or complete bowel obstruction. The fi rst symptoms may thus be of bowel obstruction with intermittent griping abdominal pain (colic), constipation and abdominal distension. Other features of large bowel cancer may be of general debility, weight loss, tiredness and lassitude (sometimes due to anaemia) or features of liver enlargement or jaundice due to liver metastases. It may be possible to feel an abdominal lump or localised swelling or on anal examination with a gloved finger, a mass in the anus or lower rectum can sometimes be felt. There may be evidence of blood in the faeces. In obstructive bowel cancer, colic with abdominal distension or swelling is likely. Staging of Colon Cancer The process of staging a colon cancer is based on the American Joint Committee on Cancer (AJCC) TNM. T (Tumor) CATEGORIES FOR COLORECTAL CANCER The T stage describes the extent through the bowel wall that the cancer spread. The N (Nodes) stage describes the presence of regional nodal metastases Tx. No description of the tumor’s extent is possible because of incomplete information. Tis. The cancer is in the earliest stage. It involves only the mucosa. It has not grown beyond the muscularis mucosa (inner muscle layer) of the colon or rectum. This stage is also known as carcinoma in situ or intramucosal carcinoma. 7 T1. The cancer has grown through the muscularis mucosa and extends into the submucosa. T2. The cancer has grown through the submucosa, and extends into the muscularis propria. T3. The cancer has grown completely through the muscularis propria into the subserosa but not to any neighboring organs or tissues. T4. The cancer has spread completely through the wall of the colon or rectum into nearby tissues or organs. N CATEGORIES FOR COLORECTAL CANCER N categories indicate whether or not the cancer has spread to nearby lymph nodes and, if so, how many lymph nodes are involved. Nx. No description of lymph node involvement is possible because of incomplete information. N0. No lymph node involvement is found. N1. Cancer cells found in one to three regional nodes. Regional nodes depend upon the location of the colon cancer and are located along the course of major vessels supplying the colon, along the vascular arcades of the marginal artery, and along the mesocolic border of the colon. N2. Cancer cells found in four or more regional lymph nodes. M CATEGORIES FOR COLORECTAL CANCER M categories indicate whether or not the cancer has spread to distant organs, such as the liver, lungs, or distant lymph nodes. Mx. No description of distant spread is possible because of incomplete information. M0. No distant spread is seen. M1. Distant spread is present. TREATMENT Surgical Management At presentation, the initial evaluation should consist of routine chemistries and a complete blood count. An elevated carcinoembryonic antigen (CEA) preoperatively is associated with a poor prognosis. The routine use of imaging is controversial. It is reasonable to obtain CT scans of the chest, abdomen, and pelvis to evaluate for the presence of metastatic disease. For patients with stage I, II, or III colon cancer, surgical resection of the colon cancer is the mainstay of therapy. Open colectomy or laparoscopic colectomy is equally effective. For patients with stage IV colon cancer who are not considered candidates for cure, resection of the primary lesion can be based upon the symptoms of the patient. In the asymptomatic patient, surgical resection of the primary tumor is not 8 necessary and can be deferred until the patient experiences local symptoms. Some patients will die of metastatic disease without ever experiencing symptoms from the primary tumor. Stage 1 Surgical resection cures >90% of patients with stage 1 colon cancer. Adjuvant therapy is not recommended. Patients should undergo surveillance colonoscopy within 3–5 years of diagnosis. Patients with more than two firstdegree relatives with colon cancer, a first-degree relative with colon cancer under the age of 50, or who are under 50 themselves, should undergo evaluation in a genetic/high-risk clinic. Stage 2 Surgical resection cures approximately 80% of patients with stage 2 colon cancer. The use of adjuvant chemotherapy is controversial and is currently not recommended by the American Society of Clinical Oncology. Randomized studies have not shown a statistically significant benefit for the use of adjuvant chemotherapy in patients with stage 2 colon cancer. However, many experts advocate for the use of adjuvant chemotherapy in high-risk patients, because these patients carry a greater than 20% risk of dying from recurrent disease. Patients with stage 2 colon cancer who are considered high risk carry the following features • T4 disease • Presentation with perforation or obstruction • Inadequate nodal evaluation; the American College of Pathology recommends that at least 12 regional lymph nodes be examined for the presence of nodal metastases • Poorly differentiated tumors For type of adjuvant chemotherapy see stage 3 section below. Stage 3 Surgical resection cures approximately half of patients with stage 3 colon cancer. Patients with N1 disease can expect a cure rate with surgery alone of approximately 60–70%. Patients with N2 disease can expect a cure rate of 30% with surgery alone. Adjuvant chemotherapy is recommended for all patients with stage 3 colon cancer at improved overall survival. Standard treatment can consist of 6 months of 5-fluorouracil (5FU) and leucovorin. Six months of capecitabine, an oral fluoropyrimidine, has equivalent efficacy to intravenous 5FU and leucovorin. Recently, the addition of oxaliplatin to intravenous 5FU and leucovorin has been associated with an improved disease-free survival compared with 5FU and leucovorin for patients with stage 2 and 3 colon cancer. Subset analysis of patients with stage 2 disease did not reveal a statistically 9 significant advantage in disease-free survival for patients receiving FOLFOX compared with 5FU and leucovorin. Stage 4 All patients with isolated liver or lung metastases should be evaluated by a surgical specialist for consideration of resection of the metastases. Approximately 30% of patients undergoing complete resection of isolated liver or lung metastases will be cured. For patients in whom a curative resection cannot be done, the median survival is approximately 6–8 months without chemotherapy and 2 years with chemotherapy. Approximately 10% of patients who undergo aggressive chemotherapy will live for 5 years. Until 1997, 5FU was the only active chemotherapy. Studies demonstrated that the addition of folinic acid (leucovorin) to 5FU improved the response rates and time to tumor progression. Since 1997, irinotecan, oxaliplatin, bevacizumab, and cetuximab have been approved for use in patients with metastatic colon cancer. First-line chemotherapy for patients with metastatic disease of consists of either FOLFOX (5FU, leucovorin, oxaliplatin) or FOLFIRI (5FU, leucovorin, irinotecan) with bevacizumab. Second-line chemotherapy typically consists of either an irinotecan-based regimen if FOLFOX was used as the first-line regimen, and an oxaliplatin-based regimen if FOLFIRI was used as the first-line regimen. Cetuximab is approved for use either alone or in combination with irinotecan for patients who had previously progressed on an irinotecan containing regimen. Capecitabine is often substituted for 5FU and leucovorin in the FOLFOX regimens. The median survival for patients with metastatic disease receiving all available therapy is approximately 2 years Suggested Reading: 1. Manual Of Clinical Oncology, - Dennis A. Casciato, Barry B. Lowitz, 2000 2. Oxford Handbook of Oncology, - Oxford University Press, 2002 3. Basics of Oncology, - Frederick O. Stephens · Karl R. Aigner, 2009 4. HARRISON’S Manual of Oncology, - Bruce A. Chabner, Thomas J. Lynch, Jr., Dan L. Longo, 2008