1. Department Of General And Minimal Invasive Surgery .POLYPOSIS SYNDROMES INCOLORECTUMPresenter: Dr. Muzzain Iqbal Khateeb.Moderator: Dr. Fazl .Q .Parray.Postgraduate Seminar Presentation

2. A colorectal polyp is any massprojecting into the lumen of thebowel.Polyps are further categorizedaccording toi. Size.ii. Character of their attachmentto bowel wall.iii. Cellular architecture.iv. Histological appearance. 3. POLYPS WITH LARGER MASS HAVEGREATER VOLUME OF NEOPLASTICCELLS ,HENCE A HIGHERLIKELIYHOOD OF HARBORINGCANCER.POLYP SIZE(mm)42NUMBER513735811069516219677% WITH INVASIVECARCINOMA02.218.642.863.978.9 4. Depending upon attachment tobowel wall, polyps can be1) Pedunculated:with stalk2) Sessile: withoutstalkNote: the way in which polyp is attached to the wall does not accurately predictthe presence verses absence of invasive malignancy. 5. Polyp architectureAdenomatousTubularTubulovillousVillousNon adenomatousHyper plasticHamartomatousInflammatory polyps 6. Adenomatous polyps:Are commonThese lesions are dysplastic, so shouldbe treated as premalignant.Based on extent to which dysplasticepithelium is organized these can be 7. 1)Tubular:Found any where incolon.Approx 65%-85% of alladenomatous polyps.Most oftenpedunculated.Have less atypia,associated withmalignancy in only 5%of cases.Pedunculated tubularadenoma 8. 2)Tubulovillous10%-25% of adenomatous polyps Commonly found in the rectalarea.Are at intermediate risk (22%)of malignancy 9. 3)Villous: most commonly occur in therectal area. Least common about 5%-10%. Most often sessile. Generally have severe atypia ordysplasia, may harbour cancer inup to 40%. They tend to be larger than theother two types.1 cm sessile villousadenoma of the sigmoidcolon. 10. Associated with the highest morbidity andmortality rates of all polyps.Can cause hyper secretory syndromes :hypokalemia and profuse mucous dischargeCan harbor carcinoma in situ or invasivecarcinoma more frequently than otheradenomas. 11. Clinical presentation andnatural history of AdenomasAdenomas are generally asymptomaticand are most often detected by coloncancer screening tests.Small adenomas do not typically bleedAdvanced adenomas are more likely tobleed and cause a positive fecal occultblood test. 12. Advanced pathologic risk factorsAdenomatous polyps >1 cm in diameterAdenomatous polyps with high-gradedysplasiaAdenomatous polyps with >25 percentvillous histology 13. Adenoma carcinomasequencePeak incidence fordiscovery of benigncolorectal polyp is 50yrs an development ofcolorectal cancer is60yrs: s/o 10 yrs span forprogression ofadenomatous polyp tocancer 14. Haggits and colleagues have proposed classification for polypscontaining cancer acc to depth of invasion as:Level 0: Carcinoma does not invade themuscularis mucosa (ca in-situ)Level 1: carcinoma invades head ofpedunculated polyp(invades throughmuscularis mucosae)Level 2:invasion into neckLevel 3:invasion into stalkLevel 4:invasion into base.(invadessubmucosa)By defination ,all sessile polyps withinvasive carcinoma are level 4. 15. Depth of submucosal invasion in sessilemalignant polyps.Sm1: invasion into upper thirdSm2: invasion into middle thirdSm3:invasion into lower third. 16. Polyposis syndromes Familial adenomatous polyposis (FAP).-Gardner syndrome.-Turcot syndrome. Hereditary nonpolyposis colorectal cancer (HNPCC). Peutz-Jeghers syndrome. Juvenile polyposis syndome. Cowden disease. Hyperplastic polyposis syndrome. Cronkite-Canada syndrome. Bannayan-Riley-Ruvalcaba Syndrome. 17. AdenomatousFAP HNPCCPolyposis syndromes 18. Hamartomatous polyposissyndromesJuvenilepolyposissyndome.Peutz-Jegherssyndrome.Cowdendisease.Bannayan-Riley-RuvalcabaSyndrome.Cronkite-Canadasyndrome. 19. 1.Familial adenomatous polyposis (FAP)Prototypical hereditarypolyposis syndrome.Autosomal dominant.Frequency about1:10,000.Account for about 1% ofall colorectal cancers. 20. The APC gene:The adenomatous polyposis coli (APC) gene is atumour suppressor gene located on chromosome5q21. Mutation in APC gene is genetic basis attributed toa truncating mutation in the germ-line APC gene.The gene expression is 100% in patients with themutation.GENETICS 21. The presentation and severityof disease is related to the siteof the APC gene mutation.Proximal APC mutations(proximal to codon 1249)produce a milder attenuatedphenotype with sparsepolyposis.APC mutations betweencodons 1250 and 1330 presentwith tremendous degrees ofpolyposis. 22. APC is universally expressed but mRNA is found inparticularly high levels in normal colonic mucosaWeighs 300-KDa: found in cytoplasmAPC binds and down regulates cytoplasmic b-catenin,preventing its translocation to nucleus.Abnormal APC protein fails to do this, so that b-catenin is free to enter the nucleus and form acomplex which results in specific transcription of cellcycle stimulating DNA sequences, and henceproliferation.The APC protein 23. Common expression of syndrome is: Multiple colonic polyps(>100) Polyps start after age 1020, cancer in100% at age 40.All patients will develop cancer of colonif left untreated. 24. Extra colonic manifestations 25. Gastric polyp :mostly are fundic glandhyperplasia and have limited malignantpotential.Duodenal polyp: adenomatous thuspremalignant.Duodenal cancer and desmoid disease are majorsources of morbidity and mortality.Increased risk of adenocarcinoma in theperiampullary region in 310% of patients 26. Interesting marker isCHRPE( congenitalhypertrophy of retinalpigment cells).It is a patchy fundusdiscoloration.Detected by indirectophthalmoscopy in 75% ofpatients. 27. Colonoscopicview ofhundreds ofpolyps in apatient ofFAP 28. A portion of a colectomy specimenthat shows complete carpeting ofthe mucosal surface byadenomatous polyps. 29. Polyposis syndromes recognized tobelong to general disorder of FAPinclude Gardners syndrome. Turcots syndrome. 30. Gardner syndrome (GS)Characterized byColonic adenomatous polyposis Osteomas: usually present in skull, mandible,and tibia They are virtually always benign.Soft tissue tumours like epidermoid cysts,fibromas, desmoid tumors. 31. Desmoid tumors canpresent in theretroperitoneum andabdominal wall of affectedpatients These tumors seldommetastasize but are oftenlocally invasive, and directinvasion of the mesentericvessels, ureters, or walls ofthe small intestine canresult in death. 32. Extra oralosteomas 33. Mandibular osteoma in apatient with Gardnerssyndrome.Radiograph of a mandibledemonstrating mandibularosteoma. 34. Turcot syndromeIncludes polypsMedulloblastomaCongenitalhypertrophy of theretinal pigmentedepithelium[CHRPE]Glioblastomamultiforme. 35. MYH POLYPOSISAn autosomal recessive form of FAP.Caused by mutation in the MutY homolog(MYH) gene.Individuals have fewer than 100 polypsColonic microadenomas and duodenal adenomasare present.Diagnosis is considered in families where No APC mutation have been identified The mode of inheritance is not clearly autosomal dominant Polyp numbers are low. 36. Attenuated familial adenomatous polyposis(AFAP).Approximately 25% of FAP patients remain withoutan identified APC mutationHave lower polyp number(1-50)Later age at diagnosisTendency to spare the rectum.Lower extra colonic manifestations. 37. DiagnosisGenetic testing:DNA from an individual with FAP is analysed to identifya mutation in APC, which is successful in about 80% ofcases.Failure to detect an APC mutation does not exclude adiagnosis of FAP, and may occur for a variety of reasonsincluding gene deletion AND some missense mutation. 38. Polyposis registries Aim: to provide counseling, support and clinical services forfamilies with FAP. This includesi. Thorough pedigree analysis and identification of at-riskfamilyii. Members, who are offered clinical surveillance and genetictesting so that those affected can be offered prophylacticsurgery Studies suggest that the introduction of registries, togetherwith the use of prophylactic surgery, has led to increased lifeexpectancy and a dramatic reduction in the incidence ofcolorectal cancer in FAP 39. Surveillance Colonoscopy every 12 months starting at aroundage 10 to 12 and continuing until age 35 to 40 ifnegative. Flexible proctosigmoidoscopy at age 10-12 year;repeat every 1-2 yr until age 35; after age 35 repeatevery 3 yr Upper GI endoscopy every 1-3 yr starting whenpolyps first identified 40. Familial Adenomatous Polyposis (FAP)SCREENINGRECOMMENDATIONSColorectal cancer 100% Colonoscopy annually, beginningage 10-12 yrDuodenal orperiampullary cancer5%-10% Upper GI endoscopy every 1-3 yr,beginning age 20-25 yrPancreatic cancer 2% Possible periodic abdominalultrasoundThyroid cancer 2% Annual thyroid examinationGastric cancer