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General Reference ⬇

Nejm 2000;342:1960

Pathophys and Cause ⬆ ⬇

Cause:Neoplasia; at least 20% are clearly genetic (Nejm 1985;312:1540), a small % autosomal dominant

Epidemiology ⬆ ⬇

After lung, 2nd most common cancer in US; 6% lifetime risk, 130 000 incidence/yr in US, 60 000 die/yr in US. Most arise from adenomatous polyps over years and decades (Ann IM 1993;118:91), not hyperplastic polyps? (Ann IM 1990;113:760 vs Nejm 2000;343:162, 169). Adenomatous polyps themselves are associated w high-animal-fat, low-fiber diets (Ann IM 1993;118:91); lower adenoma/cancer rates w increased dietary fiber (Nejm 1999;340:169, 223) but not after control for other risk factors (Jama 2005;294:2849), nor does it decr recurrence after 1st polyp removed (Nejm 2000;342:1149, 1156). Also much harder to distinguish “FLAT POLYPS”, 5-10% prevalence, 10x higher malignancy likelihood (Jama 2008;299:1027)

Associated with family h/o cancer or adenomatous polyps (Ann IM 1998;128:900; Nejm 1996;334:82) in a 1st-degree relative, 2-5 (5, under age 45 yr) × baseline rate if 1 such relative; autosomal dominant multiple gi polyposis syndromes (adenomatous or hamartomatous or nonpolyposis syndromes) (Nejm 2003;348:919): FAMILIAL COLONIC POLYPOSIS and TURCOT (colonic polyps and CNS tumors—Nejm 1995;332:839) SYNDROMES (gene defects on chomosome 5—Nejm 1993;329:1982; 1990;322:904); GARDNER’S SYNDROME with pigmented retinal lesions (Nejm 1987;316:661); and PEUTZ-JEGHERS SYNDROMEof hamartomas throughout the gi tract, pigmented spots on lips, with gi bleeding and GI as well as breast and gyn cancers developing in >50% (Ann IM 1998;128:896; Nejm 1987;316:1511); HEREDITARY NONPOLYPOSIS COLORECTAL CANCER (HNCC) (Jama 2005;294:2195, 293:1979, 1986, 2028; Ann IM 2003;138:560), hereditary nonpolyposis colon cancer 80% lifetime risk, and cancer of endometrium, ovary (Nejm 2006;354:261, 293), stomach, small bowel, biliary tree. Polyposis syndromes are generally associated with distal cancers, whereas nonpolyposis genetic types are associated with proximal cancers and other cancers (esp endometrial) in the same patient and 1st-degree relatives and have defects in DNA repair genes (Nejm 1998;338:1481)

Also associated with Streptococcus bovissepticemia, cancer is present 85% of the time (Ann IM 1979;91:560); ulcerative colitis sx >10 yr (Ulcerative Colitis); elevated cholesterol in men (Ann IM 1993;118:481)

Not associated with inguinal hernia (Nejm 1971;284:369)

Signs and Symptoms ⬆ ⬇

Sx:Change in bowel habits; blood in stool or on toilet paper (ask in ROS, positive response assoc w 24% prevalence of significant pathology—Jama 1997;277:44); abdominal cramps and other obstructive sx early with left-sided tumor, late with right-sided tumor

Si:Acanthosis nigricans (see Carcinoma of Stomach (Stomach Cancer) for differential dx); palpable rectal or abdominal mass; blood in stool, gross or by guaiac

Course ⬆ ⬇

Duke's stage A(I); T1-2N0M0: confined to submucosal area, 90% 5-yr survival with surgery

Complications ⬆ ⬇

Metastases; Strep. bovisendocarditis (Ann IM 1979;91:560; Nejm 1977;297:800)

r/o ANAL CANAL CANCER (Jama 2008;299:1914; Nejm 2000;342:792) caused by HPV, rx’d w radiation and chemRx (5 FU + mitomycin)

Lab and Xray ⬆ ⬇

Lab:

Endo:Colonoscopy age 50-75 yr in average-risk individuals for primary prevention (Colon Cancer)

Colonoscopy q 3-5 yr in patients who have had an adenomatous polyp removed (Nejm 1993;328:901) whether large or small since 30% will have proximal neoplasia (Nejm 1997;336:8)

Colonoscopy q 10 yr if no polyps found.

Path:Histologic staging as above, each worse if blood vessel invasion

Adenomatous and/or villous polyps deserve full bowel w/u (Jama 1999;281:1611)

COX-2 levels to guide post-op ASA prevention?

Serol:CEA to monitor for recurrence but does not change survival

Stool:Screening occult blood testing ages 50-75 yr in those of average risk: yearly screening with 3 stool-card protocol; single FOBT test less helpful for screening (Colon Cancer)

Xray:CT colonoscopy if colonoscopy unsuccessful; expensive, high-radiation load, and very dependent on prep for sensitivity, 85% sensitive and 88% specific in high-risk groups with less risk associated with perforation and sedation (Jama 2009;301:2453, 2498)

Treatment ⬆

Rx:

Prevent w:

  • ASA 81-325 mg po qd or biw-tiw (Nejm 2003;348:883, 891) w greater benefit w higher doses up to 650 mg po qd reduces risk by 50% (Jama 2009;302:649), vs. no increased benefit with doses >75 mg daily (Lancet 2010; 376:1741-50), or other NSAIDs like ibuprofen (Gastroenterol 1998;114:441; Nejm 1995;333:609), sulindac (Clinoril) (Ann IM 1991;115:952 vs Nejm 2002;346:1054); all shown to decr recurrent polyps but may not be worth the bleeding risks, probably work by inhibiting cyclooxygenase (COX-2) found in aggressive colon Ca (Nejm 2000;342:1960; Jama 1999;282:1254). Using COX-2 inhibitors not worth the cardiovascular risk (Nejm 2006;355:873, 885, 950). None work in Lynch syndrome (Nejm 2008;359:2567)
  • Folate qd × yrs may reduce absolute risk × 30% after 15 yr (NNT-15 = 3) (Ann IM 1998;129;517) vs increases polyp growth rate?
  • Perhaps genetic screening for adenomatous polyposis coli gene if pos fam hx (Nejm 1997;336:823); Calcium qd in low-fat dairy products? (Nejm 1999;340:101)
  • Not: Vits E, C, and A (ß-carotene) (Nejm 1994;331:141); not low-fat diets (Jama 2006;295:643)

Surgical excision by laparotomy or colonoscopy; prophylactic removal of adenomatous polyps, even those <1 cm (Nejm 1993;329:1977) decreases cancer rate by 75-90%.

Chemotherapy (Nejm 2005;352:476; 2004;350:2406; Med Let 2004;49:46) postop for stage C(III) w adjuvant 5-FU and levamisole + radiation

Palliation of advanced disease prolongs median survial from 2 mo w 5-FU alone to >21 mo, but is it worth the $15K/mo cost? (Nejm 2004;351:317, 337)

f/u after resection beyond pursuit of sx and q 3-5 yr colonoscopyafter resection beyond pursuit of sx and q 3-5 yr colonoscopy not justified (Nejm 2004;350:2375)

of liver mets: resection then hepatitic artery chemoRx (Nejm 1999;341:2039)

in rectal cancer, preop radiation (Jama 2000;284:1008; Nejm 1997;336:980) and chemoRx? (Nejm 2004;351:1731 vs 2006;355:1114) and AP resection, but latter has postop sexual dysfunction in 1/3; pre- or postop 5-FU does not prolong survival but decreases local recurrences (Nejm 2006;355:1114)