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Forms of colorectal cancer?
- Hereditary – Family history present, young age at onset, presence of other specific tumor and defect,
- Sporadic – Absence of family history, affect older population
- Familial – Life time risk for colorectal cancer increases for memebers – family in which the index case is young (<50 yrs) and relative is close (first degree relative)
Describe adenoma carcinoma sequence in colorectal carcinoma. [Tu 2063/6]
Fearon Vogelstein adenoma carcinoma multistep model of colorectal neoplasia?
Normal colonic epithelium – APC – Dysplastic abberent crypt focil – Early adenoma – k-ras – Intermediate adenoma – DCC – Late adenoma – p53 – Carcinoma [@ A KaliDas Poudel]
Observations that provide support of adenoma carcinoma sequence?
- - Large adenoma are found to harbor cancer more often than smaller ones and larger the polyp, the higher the risk of cancer
- - Residual benign adenomatous tissue is found in most invasive colorectal carcinoma
- - Benign polyp has been observed to develop into carcinoma
- - Colonic adenoma occur more frequently in patients who have colorectal cancer
- - Removal of polyp decreases the incidence of carcinoma
- - Population of high risk of colorectal carcinoma also have a high prevalence of colorectal polyp
- - Patients with FAP will develop colorectal carcinoma in almost 100% of cases in absence of surgical intervention
- - The peak incidence of discovery of benign colorectal polyp is 50yrs of age. The peak incidence of developing colorectal cancer is 60 years of age. This suggest 10 yrs time span for progression of adenomatous polyp to carcinoma
How do you classify colorectal polyps. What are the treatment modalities of colorectal polpys. [TU 2065/4]
Classification of colorectal polyp?
- 1) Neoplastic
- - Tubular adenoma
- - Villous adenoma
- - Tubulovilous adenoma
- - Serrated adenoma
- 2) Hyperplastic
- 3) Hemartomatous
- - Peutz Jeger Syndrome
- - Cronkite canada
- 4) Inflammatory
- - Pseudopolyp (ulcerative colitis)
- - Benign lymphoid polyp
Types of colorectal polyp?
- Tubular – branched tubular gland, most common (65-80%), pedunculated, less atypia
- Villous – long finger like projection of surface epithelium, 5-10%, sessile, severe atypia
- Tubulo-villous – Both cellular pattern (10-25%)
Treatment of polyp?
- Pedunculated – removal with snare
- Sessile – Segmental colectomy
What is invasive colonic Carcinoma?
Invasion of muscularis mucosa
Invasion level of polypoideal lesion by Haggitt?
- Level 0 – Mucosal invasion superficial ot muscularis mucosa
- Level 1 – Submucosal invasion, limited to the head of the polyp
- Level 2 – Submucosal invasion of the neck
- Level 3 – Submucosal invasion anywhere in the stem
- Level 4 – Submucosal invasion below the stem without reaching the muscularis propria
Note – all sessile polyp with invasive carcinoma are level 4 by Haggitt criteria.
Poor prognostic factors for polyp?
- Poorly differentiated
- Lymphovascular invasion
Hereditary colonic carcinoma syndromes?
- Familial adenomatous polyposis
- Lynch syndrome
- Juvenile polyposis syndrome
Write short note on FAP. [TU 2064,65,70,71,72]
What is FAP?
- FAP is the prototypical hereditary polyposis syndrome.
- APC gene, located on chromosome 5q21 is responsible for FAP
Features of FAP?
- Intestinal polyp - Multiple colonic polyp, gastric, duodenal and periampullary polyp
- Extraintestinal manifestations – epidermoid cyst, desmoid tumors, osteoma, brain tumors
- Gardner syndrome – Colonic polyp + Osteoma + Epidermal inclusion cyst
- Turcot Syndrome – Colonic polyp + Brain tumors [@ Turcot - Topi - In Head - brain]
- (Gardner and Turcot syndromr belong to FAP syndrome)
Treatment of FAP?
- Restorative Proctocolectomy with IPAA accompanied with distal rectal mucosectomy,to ensure that all premalignant colonic mucosa is removed, most commonly recommended operation. The incidence of inflammation in the ileal pouch (pouchitis) is much lower in patients with FAP than in patients with ulcerative colitis.
- Total abdominal colectomy with ileorectal anastomosis – procedure of choice before era of IPAA
Significance of genetic testing (codon 1250) in management of FAP?
- Mutation before 1250 – Abdominal colectomy with Ileorectal anastomosis
- Mutation after 1250 – Restorative proctocolectomy with IPAA
Management of Intestinal manifestations of FAP?
- Colonic Polyp
- Gastric polyp – Hyperplastic, do not requires surgical removal
- Duodenal polyp – Neoplastic, GI surveillance every 2 years, polypectomy. If Ampullary – Whipples
Management of Abdominal desmoid tumor in FAP?
- Small desmoid tumors – resection
- Mesenteric desmoid – Surgical treatment is dangerous and generally futile. Treatment with Sulindac, Tamoxifen, low dose of methotrexate, radiation
Clinical criteria for HNPCC. [TU 2071]
Amsterdam criteria for HNPCC?
- At least 3 relatives of colon cancer and all of the following –
- 1. One affected person is a first degree relative of two other affected persons
- 2. Two successive generation is affected
- 3. At least one case of colon cancer diagnosed before age 50 years
- 4. FAP excluded
Modified Amsterdam criteria for HNPCC?
- Same as Amsterdam criteria, except that cancer to be included to not only colorectal, but also endometrial, ovarian, gastric, pancreatic, small intestinal, urethral or renal pelvis
- Further liberalization for identifying HNPCC occurred with introduction of Bethesda criteria.
Management of Lynch syndrome?
- Close surveillance
- Surveillance colonoscopy begins at age 20 years – every 2 years till 35 years, then annually – removal of polyp when found
- Periodic vacuum curettage at age 25 years, pelvic ultrasound and CA-125 level
- Annual test for occult blood for urine – for urethral and renal pelvic carcinoma
- If cancer detected,
- Abdominal colectomy with ileorectal anastomosis
- Prophylactic TAH with BSO for family completed women
- Annual proctoscopic examination
Difference between development of cancer in FAP and HNPCC?
- In FAP – Accelerated tumor initiation (APC mediated), Normal tumor progression (RAS, p53 mediated)
- In HNPCC – Normal tumor initiation, Accelerated tumor progression
- In HNPCC, even with annual colonoscopic examination, there is a documented risk of colon cancer, but, when the cancer arises while the patient is under vigorous surveillance, the cancer stage is usually favorable.
Peutz- Jegher syndrome?
- Hemartomatous polyp of intestinal tract
- Hyperpigmented buccal mucosa, lips and digits
Short note on Npouch colon. [TU 2073]