Colorectal cancer

Krista Brūna, MF V

About...

• Colorectal cancer - starts in the large intestine (colon) or the rectum. Almost all colon cancers start in glands in the lining of the colon and rectum.[1]

• CRC is the 3rd most common cancer in men and 2nd in women. 55% occur in more developed countries.[2]

• 5 year life expectancy depends of the stage CRC is detected.• localized stage – 90%, • regional -70%, • distant metastatic disease -10%.[3]

GLOBOCAN 2012: Estimated Cancer incidence, Mortality and Prevalence Worldwide in 2012*[2]

* Estimated numbers (thousands)

Men Women

GLOBOCAN 2012: Estimated Cancer incidence, Mortality and Prevalence Worldwide in 2012. http://globocan.iarc.fr/Pages/fact_sheets_cancer.aspx

Nonmodifiable risc factors[3]

• Age (likelihood increases >40 years, sharp rise >50 years)

• Personal history (adenomatous polyps)

• Inflammatory bowel disease (Crohn’s, Ulcerative colitis)

• Family history (CRC or adenomatous polyps)

• Inherited genetic risk

The adenoma-carcinoma sequence in sporadic and hereditary colorectal cancer. (From Ivanovich JL, Read TE, Ciske DJ, et al: Am J Med 107:68-77, 1999.)

Hereditary cancer syndromes[4]

• HEREDITARY NONPOLYPOSIS COLON CANCER

• HEREDITARY ADENOMATOUS POLYPOSIS SYNDROMES• Familial Adenomatous Polyposis/Gardner's Syndrome• Turcot's Syndrome

• HEREDITARY HAMARTOMATOUS POLYPOSIS SYNDROMES• Cowden's Disease• Familial Juvenile Polyposis• Peutz-Jeghers Syndrome• Ruvalcaba-Myhre-Smith Syndrome (Bannayan-Zonana

Syndrome)

Townsend:Sabiston Textbook of surgery ,18th ed. 2007, Elsevier. Chapter:50.

Environmental risc factors• Studies of immigrants and their offspring ( from low-risk

countries to high-risk; incidence increases toward that of the host country).[3]

• Nutritional practices• High level of processed and /or red meat intake (20% increased

risk).[5]

• In most publications, “red meat” gathers beef, veal, mutton, pork and offal, and “processed meat” (equivalent: deli meat) gathers cooked, dried, smoked, or cured meat and offals from any animal, but mostly pork.[7]

• Possible underlying mechanism – heme iron in red meat, heterocyclic amines and polycyclic aromatic hydrocarbons (when cooked at high t0) – possible carcinogenic properties.[3]

• Current WCFR-AICR recommendations <500 g per week red meat, to avoid processed meat.[7]

• Physical activity and Obesity• Regular physical activity and a healthy diet can help decrease the

risk of colorectal cancer, although the evidence is stronger for colonic than for rectal disease.[3]

• Protective effect slightly stronger in men than women (22% for men and 13% for women).[5]

• Sustained moderate physical activity raises the metabolic rate and increases maximal oxygen uptake. [3]

• Several biologic correlates of being overweight or obese, notably increased circulating estrogens and decreased insulin sensitivity, are believed to influence cancer risk, and are particularly associated with excess abdominal adiposity independent of overall body adiposity.[3]

• Alcohol consumption• For heavy drinkers risk is increased for 60% than in light or non-

drinkers.[5]

• Acetaldehyde (alcohol metabolite) is a possible carcinogen.[8]

• Alcohol may also function as a solvent, enhancing penetration of other carcinogenic molecules into mucosal cells.[8]

• Cigarette smoking• The carcinogens found in tobacco increase cancer growth in the

colon and rectum, and increase the risk of being diagnosed with this cancer.[3]

• Cigarette smoking is important for both formation and growth rate of adenomatous polyps, the recognized precursor lesions of colorectal cancer.[9]

• Mean age of patients with CRC who did not smoke or drink being 71.3 years, while the mean age of current drinkers and smokers was 62.6 years.[10]

Clinical presentation[11]

• Patient with CRC may present in 3 ways:• Patients with suspicious symptoms and/or signs

• Asymptomatic individuals discovered by routine screening

• Emergency admission with intestinal obstruction, peritonitis, or rarely, an acute gastrointestinal (GI) bleeding;

• Symptoms of CRC are typically due to growth of the tumor into the lumen or adjacent structures, and as a result, symptomatic presentation usually reflects relatively advanced CRC.

Signs and symptoms

• Hematochezia or melena – hematochezia more common in rectosigmoid location. [11]

• Change in bowel habit – passage of loose stool or increased frequency of defaecation (60-91% in distal CRC, 40-61% in proximal CRC); constipation not so common.[12]

• Iron deficit anemia – common, more frequent in right sided CRC (65-80%)[12], which cause greater blood loss (9ml/day).[11]

• Weight loss - 5% of body weight in 6-12 months.[12]

• Abdominal pain – nonspecific. More common for proximal cancer (45-90%), than distal (10-15%). Nonspecific pain and rectal bleeding / diarrhea / weight loss – caution necessary.[12]

• Palpable mass – rectal cancer, right iliac fossa.[12]

• Abdominal distention and/or nausea, vommiting – rarely, indicators of possible obstruction.[11]

• Right sided tumors– exophytic mass (grows outward in the lumen).

• Left sided tumors- endophytic mass (grows inward, «apple core» sign).

• Obstructive symptoms more common in tumors that constrict the lumen circulary.[11]

http://library.med.utah.edu/WebPath/GIHTML/GI116.html

Differential diagnosis [13]

• Inflammatory bowel disease• Irritable bowel syndrome• Diverticulosis• Gastrointestinal lymphoma• Haemorrhoids

Diagnostic

• Patients with suspicous symptoms or signs[1]

• Anamnesis • Physical evaluation (sometimes a palpable mass) • Occult blood test• Colonoscopy (material for histology)• Additional blood tests:

• Full blood count• Liver enzymes

• Emergency admission[4]

• Double contrast barium enema• CT / MRI• Blood tests• Surgical intervention (material for histology)

• Screening for asymptomatic patients age >50 [14]

Screening [14][15]

• Aim: detect CRC in early stage, when no symptoms are present.• For people age >50 years, once a year.• Test: fecal occult blood test

• For positive result – additional colonoscopy

• Increased risc for colorectal cancer:• Family history of CRC (at 40 yrs or 10

years younger than earliest diagnosis in family)

• Inflammatory bowel disease

• Anoscopy – anus, anal canal and lower rectum.• Sigmoidoscopy – rectum, sigmoid colon.• Colonoscopy – rectum, large intestine.

4 basic tests for colon cancer: • a stool test (to check for blood); • sigmoidoscopy (inspection of the lower colon; • colonoscopy (inspection of the entire colon); • double contrast barium enema. All 4 are effective in catching cancers in the early stages, when treatment is most beneficial.[18]

Colonoscopy • Most accurate and versatile

diagnostic test for CRC.[11]

• Can localise and biopsy lesions, detect synchronous neoplasms and remove polyps.[11]

• Synchronous colorectal neoplasias - 2 or more primary tumors identified in the same patient and at the same time.[19]

Before procedure[20]

• Intestine need to be completely cleansed.• Bowel preparation:• Polyethylene glycol (PEG)

• PEG - isotonic solution. • Safe and efficiant• Large volumes

• Contraindications for PEG:• Severe general condition• Decompensated cardiac failure• Suspected intestine wall tear or inflammation• Ileus• Non-compliant patient• Dysphagia for fluids (in emergency cases nasogastric tube)

• Newer preparations:• Eziclen (sulphate-based forumulation; 1L +2L water)• Moviprep PEG with electrolyte ( 3L)

• Standard scheme for bowel preparation with PEG:[20]

• Preparation begins 1 day prior to examination

• Eating not recommended 3-4 hours before PEG administration.

• Process can take at least 12 hours.

• Last PEG portion 4 hours prior to exam.

• Standard PEG is 4 l.

• One hour prior to PEG administration all medicine per os must be discontinued.

• Additional to PEG – only non coloured, clear solutions.

• 10% of water is absorbed (400ml).

• Complete colonoscopy – visualisation of the caecum, confirmed by identification of the ileo-caecal valve and triradiate fold or by performing terminal ileoscopy. [21]

• Still images of the cecum is the preferred modality for documenting colonoscopy completion.[22]

• Photographs that depict recognizable landmarks, such as the ileocecal valve (ICV), triradiate fold, and appendiceal orifice (AO), are favored.[22]

• terminal ileal images are superior to cecal images and are comparable to terminal ileal biopsy.[22]

A still image of the cecum depicting an ilcocecal valve (ICV).[22]

A still image of the terminal ileum showing villi.[22]

A still image of the appendicel orifice. Unless surrounding structures, such as the ileocecal valve or the triradiate fold, are clearly visible in the same static image, some reviewers are unconvinced, that the image truly depicts the cecum.[22]

• Common causes of incomplete colonoscopy:[21]

• Poor bowel preparation• Obstructing disease or colitis• Excess looping/ patient intolerance• Diverticular disease

• Failure in women most often tends to occur in the sigmoid colon as opposed to the ascending colon in males. [21]

Polypectomy during colonoscopy

• In general, a colonic polyp should be removed if:[24] • it is causing clinical problems (namely, hemorrhage or

obstruction) • is thought to be malignant or premalignant • its etiology is uncertain (requiring histopatho-logic evaluation for

diagnosis).

• Research has shown that by interrupting the adenoma-carcinoma sequence, endoscopic polypectomy can prevent the development of CRC.[24]

• If possible, the method of resection should be endoscopic, as opposed to surgical, to decrease morbidity and cost.[24]

Anatomic landmarks of pedunculated and sessile adenomas. (From Haggitt RC, Glotzbach RE, Soffer EE, et al: Prognostic factors in colorectal carcinoma arising in adenomas: Implications for lesions removed by endoscopic polypectomy. Gastroenterology 89:328-336, 1985.)

• Malignant polyp – macroscopically benign appearing adenoma, in which invasive carcinoma is detected histologically in the resected specimen.[23]

• The management of malignant polyps includes colonoscopic and surgical approaches.[23]

• Patients treated with polypectomy were presumably higher risk for surgery, as reflected in age and comorbidity scores, and were more likely to have tumor characteristics that were favorable, including well differentiated cancers.[23]

• Management with polypectomy is a safe and effective strategy.[23]

Thank you for your

time!

Literature:1. Colon cancer. A.D.A.M. Medical Encyclopedia. Last reviewed: Nov 17, 2012. http://www.ncbi.nlm.nih.gov/pubmedhealth/PMH0001308/ 2. GLOBOCAN 2012: Estimated Cancer incidence, Mortality and Prevalence Worldwide in 2012. http://globocan.iarc.fr/Pages/fact_sheets_cancer.aspx 3. Colorectal Cancer Epidemiology: Incidence, Mortality, Survival, and Risk Factors. Haggar F.A., Boushey R.P. Clin Colon Rectal Surg. Nov 2009; 22(4): 191–197.

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2796096/ 4. Townsend:Sabiston Textbook of surgery ,18th ed. 2007, Elsevier. Chapter:50. 5. The impact of dietary and lifestyle risk factors on risk of colorectal cancer: a quantitative overview of the epidemiological evidence. Huxley R.R. et al. Int J

Cancer. 2009 Jul 1;125(1):171-80. http://onlinelibrary.wiley.com/doi/10.1002/ijc.24343/pdf 6. Colorectal Cancer Epidemiology: Incidence, Mortality, Survival, and Risk Factors. Haggar F.A., Boushey R.P. Clin Colon Rectal Surg. Nov 2009; 22(4): 191–197.

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2796096/ 7. Red meat and colon cancer: should we become vegetarians, or can we make meat safer? Corpet D.E. Meat Science. Volume 89, Issue 3, November 2011, Pages

310–316. http://www.sciencedirect.com/science/article/pii/S0309174011001458 8. Alcohol and cancer. Pöschl G., Seitz H.K. Alcohol Alcohol. 2004 May-Jun;39(3):155-65. http://alcalc.oxfordjournals.org/content/39/3/155.long 9. Cigarette smoking and adenomatous polyps: a meta-analysis. Botteri E. et al. Gastroenterology. 2008 Feb;134(2):388-95.

http://www.ncbi.nlm.nih.gov/pubmed/1824220710. Associations Between the Age at Diagnosis and Location of Colorectal Cancer and the Use of Alcohol and Tobacco . Zisman A.L. et al. Arch Intern Med.

2006;166(6):629-634. http://archinte.jamanetwork.com/article.aspx?articleid=410057 11. Clinical presentation, diagnosis and stagings of colorectal cancer. Ahnen D.J. et al. UpTpDate, Feb 19, 2014.

http://www.uptodate.com/contents/clinical-presentation-diagnosis-and-staging-of-colorectal-cancer 12. Symptoms and signs in patients with colorectal cancer. John S.K. et al. Colorectal Dis. 2011 Jan;13(1):17-25.

http://onlinelibrary.wiley.com/enhanced/doi/10.1111/j.1463-1318.2010.02221.x/ 13. Colon adenocarcinoma. Dragovich T. et al. Medscape reference. Last updated: Apr 16, 2014. http://emedicine.medscape.com/article/277496 14. Kas jāzina par zarnu vēzi un tā novēršanas iespējām. Leja M. 2009. http://www.onko.lv/faili/kas-jazina-par-zarnu-vezi-un-ta-noversanas-iespejam.pdf 15. Patient information: Colon and rectal cancer screening (Beyond the Basics). Fletcher R. H. UpToDate. Last updated: Dec 30, 2013.

http://www.uptodate.com/contents/colon-and-rectal-cancer-screening-beyond-the-basics 16. Anoscopy. A.D.A.M. Medical Encyclopedia. Last reviewed: Dec 10, 2012. http://www.ncbi.nlm.nih.gov/pubmedhealth/PMH0004341/17. Sigmoidoscopy. A.D.A.M. Medical Encyclopedia. Last reviewed: Oct 14, 2013. http://www.ncbi.nlm.nih.gov/pubmedhealth/PMH0004336/ 18. Colonoscopy. A.D.A.M. Medical Encyclopedia. Last reviewed: Oct 8, 2012. http://www.ncbi.nlm.nih.gov/pubmedhealth/PMH0004337/ 19. Synchronous colorectal neoplasias: our experience about laparoscopic-TEM combined treatment. Spizzirri A. et al. World Journal of Surgical Oncology 2010,

8:105. http://www.wjso.com/content/8/1/105 20. Vadlīnijas / Zarnu trakta tīrīšana kolonskopiskajiem izmeklējumiem ar polietilēnglikola šķīdumu. Darba grupa: prof. A. Danilāns, dr. J. Derova, dr. A. Derovs, dr. V.

Eglīte, prof. J. Pokrotnieks, doc. A. Puķītis. http://www.gastroenterologs.lv/lv/vadlinijas/zarnu-trakta-tirisana-kolonskopiskajiem-izmeklejumiem-ar-polietilenglikola-skidumu.html

21. Successful colonoscopy; completion rates and reasons for incompletion. Mitchell R.M.S. et al. The Ulster Medical Journal, Volume 71, No. 1, pp. 34-37, May 2002. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2475359/pdf/ulstermedj00008-0037.pdf

22. The Use of Cecal and Terminal lleal Images for Verifying the Completion of Colonoscopy. Powell N. Gastroenterol Hepatol (N Y). Aug 2011; 7(8): 536–539. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3264938/

23. Management of Malignant Colonic Polyps: A Population-Based Analysis of Colonoscopic Polypectomy versus Surgery. Cooper G.S. et al. Cancer. 2012 Feb 1;118(3):651-9. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3193545/

24. Complex Colon Polypectomy. Gallegos-Orozco J.F. et al. Gastroenterol Hepatol (N Y). Jun 2010; 6(6): 375–382. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2920588/