COLORECTAL MALIGNANCY DESCRIPTION A malignant neoplasm arising from the luminal surface of the colon, rectum or anus.

The fourth most common malignancy in the U.S. and the second most common cause of cancer-related deaths. Adenocarcinoma - by far, most common histologic form, usually arising from benign adenoma. Unequally distributed, with 38% in proximal colon and 62% in distal colon or rectum. Carcinoid - uncommon, arising from enterochromaffin cells. Usually located in appendix or rectum; not likely to metastasize unless larger than 2 cm in diameter. Squamous cell carcinoma - uncommon form; located in the anal canal. Also called epidermoid or cloacogenic. Melanoma - rare; usually presents as pigmented lesion adjacent to dentate line System(s) affected: Gastrointestinal Genetics: Hereditary colon and rectal cancer accounts for approximately 15-20% of colorectal cancer Ras oncogene mutations seen in 40-50% of adenocarcinoma; alterations of suppressor genes also seen in 75%, especially involving chromosomes 17,18 Incidence/Prevalence in USA: 155,000 new cases/year Predominant age: Adenocarcinoma usually occurs in individuals > age 50 years with peak incidence in the seventh decade Predominant sex: Male = Female SIGNS & SYMPTOMS Vary with location Early lesions are frequently asymptomatic Right-sided adenocarcinoma Anemia Pain and/or mass in right lower quadrant Occult blood in stool Change in appearance of stool (infrequent) Left-sided adenocarcinoma Change in bowel habits (may be constipation or diarrhea) Reduced caliber of stool Red blood mixed in stool Rectal adenocarcinoma Bright red rectal bleeding Tenesmus Mass on digital exam Carcinoid Often incidental fi nding Appendicitis-like if located in appendix Rectal bleeding Cramping abdominal pain Carcinoid syndrome; occurs with metastases to liver; includes facial flushing, abdominal cramps, diarrhea Squamous cell carcinoma Painful defecation Rectal bleeding Mass or ulcer in anal canal Non-healing anal fissure

CAUSES Undetermined; both genetic and environmental factors may contribute Environmental - high dietary animal fat, low dietary fiber RISK FACTORS Adenocarcinoma Two-thirds of patients are over 50 years old Pancolonic ulcerative colitis, (2% per year after 10 years active disease) Familial polyposis (100%) Hereditary nonpolyposis colorectal cancer (family history) Benign adenomas (tubular 3%; villous 9-12%) Coexisting (synchronous) colon cancer (5%) Previous (metachronous) colon cancer (2-5%) Carcinoid Multiple endocrine adenopathy (MEA), rare Other organs with carcinoid (small bowel, bronchial) Squamous cell carcinoma Bowen disease Paget disease DIAGNOSIS LABORATORY Positive fecal occult blood test Anemia Urinary 5-hydroxyindoleacetic acid (5-HIAA); elevated in carcinoid Elevated plasma carcinoembryonic antigen (CEA) Drugs that may alter lab results: Aspirin-containing medications and non-steroidal antiinflammatory drugs - positive fecal occult blood test Smoking - increased carcinoembryonic antigen Disorders that may alter lab results: Peptic ulcer disease, ulcerative colitis, hemorrhoids, benign polyps - positive fecal occult blood test Renal failure - increased carcinoembryonic antigen PATHOLOGICAL FINDINGS Adenocarcinoma May appear as ulcerated, polypoid, or fungating mass. May extend to local structures or metastasize by blood, lymphatics; staging of tumor reflects level of penetration. TNM Staging - Adenocarcinoma Stage Pathology I Invades to muscularis propria II Into serosa or adjacent organs III Regional nodes involved IV Distant metastases Carcinoid Tend to be multicentric Metastasize by blood, lymphatics Squamous cell carcinoma Most are ulcerative but may vary greatly in size Metastasize to inguinal lymphatics

SPECIAL TESTS Carcinoembryonic antigen - usually elevated with bulky tumor or metastases, useful in postoperative assessment IMAGING Computerized tomography - used to determine extent of pelvic involvement in rectal cancer; not usually necessary in colon cancer Transrectal ultrasound - useful in defi ning extent of involvement by rectal lesions Virtual colonography - using CT scanning technology the entire colon can be visualized. This does not replace the colonoscope as a means of visualizing the colon and rectum. DIAGNOSTIC PROCEDURES Anoscopy - useful for anal canal visualization, biopsies Proctoscopy/fl exible sigmoidoscopy with biopsy used for distal lesions when complementary barium enema available for proximal colon Colonoscopy with biopsy - for primary diagnosis, screening of high-risk patients and post-resection surveillance; consider as screening modality of choice in all patients TREATMENT APPROPRIATE HEALTH CARE Inpatient SURGICAL MEASURES Surgical procedures - radical resection of tumor with wide margins; includes segments of normal colon, mesentery, lymph nodes Right hemicolectomy for proximal tumors Left hemicolectomy for descending colon cancers Sigmoid colectomy for sigmoid cancers Abdominoperineal resection with colostomy for cancers of distal rectum (within 5-7 cm of dentate line) Preoperative or postoperative radiotherapy and chemotherapy: May improve outcome when used for rectal carcinoma For carcinoma of anus - combined chemotherapy (5-fl uorouracil and mitomycin C) and radiotherapy. Convert to abdominoperineal resection for residual or recurrent tumor or consider salvage chemotherapy (5-FU + cisplatin). ACTIVITY Usually normal; may be slightly modified for patient with stoma DIET Usually normal; avoidance of gas-producing foods may be helpful in ostomates (cabbage, beans, onions, alcoholic beverages) MEDICATIONS DRUG(S) OF CHOICE Steroids or somatostatin may ameliorate symptoms of carcinoid syndrome Stage III colon adenocarcinoma fluorouracil (5-FU) plus leucovorin plus oxaliplatin or CPT-11 Stage II and III rectal - 5-FU + radiation Contraindications: Peptic ulcer disease (steroids) Precautions: Refer to manufacturers literature Significant possible interactions: Refer to manufacturers literature FOLLOWUP PATIENT MONITORING Adenocarcinoma (after remainder of colon is cleared of all lesions) Colonoscopy - repeat in 1 year; then every 3 years Carcinoembryonic antigen test, liver chemistries, fecal occult blood test - every 3 months for 2 years; then every 4 months for year 3; then every 6 months for year 4; then annually Carcinoid: 5-HIAA every 6 months x 2 years, then annually

 Squamous cell carcinoma: Clinical evaluation every 4 months x 1 year, then annually Biopsy suspicious areas in anus, groin PREVENTION/AVOIDANCE Colonic polyps should be removed, examined microscopically. If benign, surveillance colonoscopy should be performed after 3 years, and if normal, every 5 years Screening - asymptomatic population (screening modalities include colonoscopy, fl exible sigmoidoscopy, and air contrast barium enema [ACBE]) Average risk (eg, > 50 years) - Flexible sigmoidoscopy every 5 years - Colonoscopy every 10 years - Barium enema every 5 years High risk (history of polyps, personal history of colorectal cancer, family history of colorectal cancer, history of IBD, FAP [familial adenomatous polyposis], hereditary nonpolyposis colon cancer) - Colonoscopy - Schedules vary depending upon underlying risk Chemoprevention (use of medical agents to prevent the development of cancer) under investigation. Aspirin and COX-2 inhibitors have shown promise. POSSIBLE COMPLICATIONS Following resections: Mortality 5-10% Wound infection 5-15% Anastomotic stricture/leak/abscess 2-5% Pneumonia 5-10% Urinary tract infection 5-20% During chemotherapy or radiation therapy: Stomatitis Proctitis/diarrhea Temporary loss of hair EXPECTED COURSE/PROGNOSIS Adenocarcinoma: Overall 5-year survival is 55% but relates to tumor stage in individual patients Five year survival for colorectal adenocarcinoma by initial stage Stage I II III IV 5-year Survival 92% 70% 50% 5%

Carcinoid: Overall 5-year survival is 65% Relates to tumor stage as in adenocarcinoma Squamous cell carcinoma: Overall 5-year survival is 79% MISCELLANEOUS ASSOCIATED CONDITIONS Colonic carcinoid - multiple endocrine neoplasia types I, II AGE-RELATED FACTORS Pediatric: Adenocarcinoma of colon occurs rarely in children; prognosis is very poor Geriatric: Coexistence of medical illness may complicate postoperative course REFERENCES Benson AB, Choti MA, Cohen AM, et al. NCCN Practice guidelines for colorectal cancer. Oncology 2000;14:203-12 Burke CA, Van Stolk R. Colorectal screening: making sense of the different guidelines. Clev Clin J Med 1999;66:303-11 Lynch HT, Smyrk R. Hereditary colorectal cancer. Semin Oncol 1999;26:478-84