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    polyposis syndromes polyposis syndromes Presentation Transcript

    • Department Of General And Minimal Invasive Surgery .“POLYPOSIS SYNDROMES INCOLORECTUM”Presenter: Dr. Muzzain Iqbal Khateeb.Moderator: Dr. Fazl .Q .Parray.Postgraduate Seminar Presentation
    • 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.
    • 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.
    • Polyp architectureAdenomatousTubularTubulovillousVillousNon adenomatousHyper plasticHamartomatousInflammatory polyps
    • Adenomatous polyps:Are commonThese lesions are dysplastic, so shouldbe treated as premalignant.Based on extent to which dysplasticepithelium is organized these can be
    • 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
    • 2)Tubulovillous10%-25% of adenomatous polyps Commonly found in the rectalarea.Are at intermediate risk (22%)of malignancy
    • 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.
    • Associated with the highest morbidity andmortality rates of all polyps.Can cause hyper secretory syndromes :hypokalemia and profuse mucous dischargeCan harbor carcinoma in situ or invasivecarcinoma more frequently than otheradenomas.
    • Clinical presentation andnatural history of AdenomasAdenomas are generally asymptomaticand are most often detected by coloncancer screening tests.Small adenomas do not typically bleedAdvanced adenomas are more likely tobleed and cause a positive fecal occultblood test.
    • Advanced pathologic risk factorsAdenomatous polyps >1 cm in diameterAdenomatous polyps with high-gradedysplasiaAdenomatous polyps with >25 percentvillous histology
    • Adenoma carcinomasequencePeak incidence fordiscovery of benigncolorectal polyp is 50yrs an development ofcolorectal cancer is60yrs: s/o 10 yrs span forprogression ofadenomatous polyp tocancer
    • 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.
    • Depth of submucosal invasion in sessilemalignant polyps.Sm1: invasion into upper thirdSm2: invasion into middle thirdSm3:invasion into lower third.
    • 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.
    • AdenomatousFAP HNPCCPolyposis syndromes
    • Hamartomatous polyposissyndromesJuvenilepolyposissyndome.Peutz-Jegherssyndrome.Cowdendisease.Bannayan-Riley-RuvalcabaSyndrome.Cronkite-Canadasyndrome.
    • 1.Familial adenomatous polyposis (FAP)Prototypical hereditarypolyposis syndrome.Autosomal dominant.Frequency about1:10,000.Account for about 1% ofall colorectal cancers.
    • 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
    • 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.
    • APC is universally expressed but mRNA is found inparticularly high levels in normal colonic mucosaWeighs 300-KDa: found in cytoplasmAPC 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
    • Common expression of syndrome is: Multiple colonic polyps(>100) Polyps start after age 10–20, cancer in100% at age 40.All patients will develop cancer of colonif left untreated.
    • Extra colonic manifestations
    • 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 3–10% of patients
    • Interesting marker isCHRPE( congenitalhypertrophy of retinalpigment cells).It is a patchy fundusdiscoloration.Detected by indirectophthalmoscopy in 75% ofpatients.
    • Colonoscopicview ofhundreds ofpolyps in apatient ofFAP
    • A portion of a colectomy specimenthat shows complete carpeting ofthe mucosal surface byadenomatous polyps.
    • Polyposis syndromes recognized tobelong to general disorder of FAPinclude Gardners syndrome. Turcots syndrome.
    • Gardner syndrome (GS)Characterized byColonic adenomatous polyposis Osteomas: usually present in skull, mandible,and tibia They are virtually always benign.Soft tissue tumours like epidermoid cysts,fibromas, desmoid tumors.
    •  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.
    • Extra oralosteomas
    • Mandibular osteoma in apatient with Gardnerssyndrome.Radiograph of a mandibledemonstrating mandibularosteoma.
    • Turcot syndromeIncludes polypsMedulloblastomaCongenitalhypertrophy of theretinal pigmentedepithelium[CHRPE]Glioblastomamultiforme.
    • MYH POLYPOSISAn autosomal recessive form of FAP.Caused by mutation in the MutY homolog(MYH) gene.Individuals have fewer than 100 polypsColonic 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.
    • Attenuated familial adenomatous polyposis(AFAP).Approximately 25% of FAP patients remain withoutan identified APC mutationHave lower polyp number(1-50)Later age at diagnosisTendency to spare the rectum.Lower extra colonic manifestations.
    • 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.
    • 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
    • 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
    • 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 <1% Upper GI endoscopy as forduodenal and periampullaryCentral nervous systemcancer<1% Annual physical examination
    • Management of large bowelOnce FAP has been diagnosed, the aim is toperform prophylactic surgeryPatients with severe polyposis or those peoplewho are symptomatic, should have surgery as soonas possible.In those individuals with milder disease, it canusually be delayed until a convenient time family. In these circumstances, annual colonoscopy isrecommended to monitor disease.
    • Choice of operationThe surgical options for the management of thiscondition are Proctocolectomy with end ileostomy (with or withoutileal pouch) Colectomy with ileoanal anastamosisProctocolectomy with ileal pouch anal anastamosis(IPAA).
    • Because few patients desire a permanentileostomy, proctocolectomy with endileostomy is rarely done.In most cases, however, the choice is betweencolectomy with IRA or proctocolectomy withileoanal pouch (IPAA) .Surgical treatment of patients with FAP isdirected at removal of all affected colonic andrectal mucosa.
    •  Restorative proctocolectomy withIPAA has become the mostcommonly recommendedoperation. The procedure is usuallyaccompanied by a distal rectalmucosectomy to ensure that allpremalignant colonic mucosa isremoved, and the IPAA is fashionedbetween the ileal pouch and thedentate line of the anal canal.
    • An alternative approach is total abdominalcolectomy with ileorectal anastomosis: hascertain advantages. Technically a simpler operation to perform Pelvic dissection is avoided. Theoretically less risk for anastomotic leak from the relatively simpleileorectal anastomosis An additional argument : sulindac and celecoxib have been observed tocause the regression of adenomatous polyps in some patients with FAP.The disadvantages are that the rectum remainsat high risk for the formation of newprecancerous polyps 12-29% after 20-25 years
    • Patients with Gardner syndromerequire surgical treatment ofCutaneous cystsSymptomatic dental anomalies and osteomasBiopsy and resection for malignancies, includinghepatoblastoma, thyroid carcinoma, osteocarcinoma,gastric carcinoma, periampullary carcinoma, and biliarytract carcinomaLiver transplantation may be required in patients withhepatoblastomaPatients with Turcot syndrome requiresurgical intervention for diagnosis and management ofCNS lesions, gastric lesions and hepatic lesions.
    • Postop surveillanceAfter IRA, the retained rectum should be examinedusing a flexible sigmoidoscope, every 6–12 months.Polyps larger than 5 mm should be removedIf severe dysplasia or uncontrolled polyposis develops,completion proctectomy with or without ileoanalpouch formation is indicated.In patients who have had IPAA, the pouch should beexamined by flexible endoscopy annually, and a carefuldigital examination of the anorectal transition zoneshould be performed.
    • ChemopreventionHave reduced the number and size of colorectaladenomasTHESE AREi. (NSAID) –sulindacii. The COX-2 inhibitor celecoxib
    • 2.Hereditary non-polyposis colon cancer(HNPCC)HNPCC is the most frequently occurringhereditary colorectal cancer syndromeAutosomal dominant. It also known as Lynch I and II syndromes.The Lynch I variants describe patients withpredominantly colorectal cancer at a young ageLynch II: those with both colorectal andextracolonic cancers.
    • Accounts for 3–5% of all colorectal cancers withpredominance of mucinous or poorly differentiated(signet cell) adenocarcinomaDespite its name, these cancers typically arisefrom colonic polyps, but a diffuse polyposis is notpresent. The penetrance of the HNPCC predisposition ishigh and results in an 80–85% lifetime risk ofcolorectal cancer and a 40–50% risk ofendometrial cancer
    • Characterized by an early onset of colorectalcancers predominantly but not exclusively onthe right side of the colon with synchronous andmetachronous cancers.HNPCC patients are at increased risk ofdeveloping extracolonic malignancies :• Cancer of the small bowel• Stomach• Hepatobiliary tract• Urinary tract• Ovary• Brain
    •  Mutations in Mismatch repairgenes (MMR ) result in theHNPCC syndrome (includinghMLH1, hMSH2, hMSH3,hPMS1, hPMS2, and hMSH6) Mutations in hMSH2 or hMLH1account for more than 90% ofcases. These mutations producemicrosatellite instability whichresult in errors in S phase whenDNA is newly synthesized andcopied. Patients with hMSH2 mutationtend to develop extracoloniccancers, in particular endometrialcancer, as compared with hMLH1mutation carriers.
    • To facilitate the clinical diagnosis of HNPCC,the International Collaborative Group onHNPCC (ICG-HNPCC) proposed theAmsterdam Criteria in 1990.
    • Amsterdam Criteria I (1990)At least three relatives with colorectal cancer,one of whom should be a first-degree relativeof the other two.At least two successive generations should beaffected.At least one colorectal cancer should bediagnosed before the age 50 years.
    • Colorectal cancer cannot beconsidered an obligate requisite todefine HNPCC , AmsterdamCriteria II, which now better weighextra colonic manifestations as part ofthe family history came intoconsidration.
    • Amsterdam Criteria II (1999)There should be at least three relatives with HNPCC-associated cancer(colorectal cancer, cancer of the endometrium, small bowel, and ureter),of which one should be a first-degree relative of the other two.At least two successive generations should be affected.At least one colorectal cancer should be diagnosed before the age 50years.
    • Further liberalization foridentifying patients with HNPCCoccurred with the introduction ofthe Bethesda criteria
    • Revised Bethesda Guidelines (2002) for TestingColorectal Tumours for MSICriterion CommentColorectal cancer diagnosed in a patient lessthan 50 years of agePresence of synchronous, metachronouscolorectal cancer, or other HNPCC-associatedtumor, regardless of ageStomach, ovarian, pancreas, ureter and renalpelvis, biliary tract, and brain, sebaceousgland adenomas and keratoacanthomas, andsmall bowelColorectal cancer with MSI-high histologydiagnosed in a patient less than 60 years ofageTumor infiltrating lymphocytes, Crohns-likelymphocytic reaction, mucinous/signet-ringdifferentiation, or medullary growth patternColorectal cancer diagnosed in at least onfirst-degree relative with an HNPCC-relatedtumor diagnosed under age 50Colorectal cancer diagnosed in two or morefirst or second-degree relatives with HNPCC-related tumors, regardless of age.
    • The mainstay of the diagnosis of HNPCC is adetailed family history.20% of newly discovered cases of HNPCC arecaused by spontaneous germline mutations, so afamily history may not accurately reflect thegenetic nature of the syndrome.Colorectal cancer, or an HNPCC-related cancer,arising in a person younger than 50 years shouldraise the suspicion of this syndrome.
    • SurveillanceHereditary Nonpolyposis Colorectal Cancer (HNPCC)Colorectal cancer 80% Colonoscopy, every 2 yrbeginning age 20 yr, annuallyafter age 40 yr or 10 yearsyounger than earliest case infamilyEndometrial cancer 40%-60% Pelvic exam, transvaginalultrasound, endometrialaspirate every 1-2 yr, beginningage 25-35 yrUpper urinary tract cancer 4%-10% Ultrasound and urinalysisevery 1-2 yr; start at age 30-35yrGallbladder and biliarycancer2%-18% No recommendationCentral nervous systemcancer<5% No recommendationSmall bowel cancer <5% No recommendation
    • MANAGEMENTWhen colon cancer is detected in a patientwith HNPCC, an abdominal colectomy andileorectal anastomosis is the procedure ofchoice.If the patient is a woman with no further plansfor childbearing, prophylactic total abdominalhysterectomy and bilateral salpingo-oophorectomy are recommended. The rectum remains at risk for developmentof cancer, and annual proctoscopicexaminations are mandatory after abdominalcolectomy.
    • Other forms of cancer associated with HNPCCare treated according to the same criteria as innonhereditary cases.The role of prophylactic colectomy for patientswith HNPCC has been considered in someinstances, but this concept has not receiveduniversal acceptance.It is an interesting but well-documented factthat the prognosis is better for cancer patientswith HNPCC than for non-HNPCC patientswith cancer of the same stage.
    • 3.Peutz-Jeghers syndrome.Autosomal dominant syndromeThe combination ofhamartomatous polyps of theintestinal tractGermline defects in the tumorsuppressor serine/threoninekinase 11 (STK11) gene areimplicated in this rare disease.
    •  Symptoms include: GI bleeding Intussusception Rectal prolapse Nasal polyposis (chronic sinusitis) Pigmented macules on thelips and digits GynecomastiaThe most common location of Peutz-Jeghers polyps is inthe upper gastrointestinal tract, specifically the upperjejunum.
    • There is also an increased risk for extraintestinalmalignancies including cancer of the breast ovary Cervix fallopian tubes Thyroid Lung Gallbladder bile ducts pancreas testicles.
    •  Mucocutaneoushyperpigmentationpresents as dark blueto dark brownmucocutaneousmacules around themouth, eyes, andnostrils, in theperianal area, on thebuccal mucosa, andon the fingers
    • PJS Diagnostic Criteria (WHO, 2010)1.3 or more histologically confirmed PJ polyps, or2. Any number of PJ polyps with a family history ofPJS,3.Characteristic prominent mucocutaneouspigmentation with a family history of PJS, or4.Any number of PJ polyps and characteristicprominent mucocutaneous pigmentation.
    • Duodenal Peutz-Jeghers polyp
    • Peutz-Jeghers Syndrome surveillanceUpper GI endoscopy 2 yearly.Small bowel radiography 2 yearly.Colonoscopy every 2 yr.Ultrasound.Haemoglobin levels annually.Gynaecologic examination, cervicalsmear, and pelvic ultrasound annually.
    • Clinical breast exam and mammography at age25 yr.Clinical testicular exam and testicularultrasound in males with feminizing features.Nasal endoscopy :to exclude the presence ofnasal polyps.Potassium titanyl phosphate (KTP) laser hasbeen used to treat mucocutaneous melanosis ofthe lips and hands in a patient with PJS
    • 4.Juvenile polyposis syndrome (JPS)Most common hamartomatous syndromeInherited as an autosomal dominant trait.A germ-line mutation in the SMAD-4 gene(18q21) accounts for approximately 50% ofthe reported cases of the syndrome.The term "juvenile" refers to the type ofpolyp, not the age of onset of polyps.
    • Characterized by predisposition forhamartomatous polyps in the (GI) tract,specifically in the stomach, small intestine,colon, and rectum.The average age of onset is approximately 18years.Associated with congenital birth defects (15%-20%) of patients including malrotation,hydrocephalus, cardiac lesions, Meckelsdiverticulum, and mesenteric lymphangioma
    •  Although the diagnostic criteriafor juvenile polyposis syndromeare somewhat controversial, themost commonly used criteriaincludei. 3 or more juvenile polyps of thecolon,ii. polyposis involving the entiregastrointestinal tract,iii. or any number of polyps in amember of a family with aknown history of juvenilepolyps.JUVENILE POLYP
    • In infancy, patients may present with acute orchronic gastrointestinal bleeding,intussusception, rectal prolapse, or a protein-losing enteropathy. In adulthood, patients commonly present witheither acute or chronic gastrointestinal bloodloss. Polyps are located most frequently in the rectosigmoid region.
    • Some individuals may only have four or fivepolyps over their lifetimes, whereas others inthe same family may have over a hundred.Most juvenile polyps are benign; however,malignant transformation can occur.Estimates of developing GI cancers in familieswith JPS range from 9-50%.
    • Juvenile Polyposis screeningScreening by age 12 yr if symptoms havenot yet arisenColonoscopy with multiple randombiopsies every several years
    • 5.Cowden syndrome Also known as multiple hamartoma-neoplasia syndrome.It is an autosomal dominant conditionComplete penetrance by the age 20.Germ-line mutations in the PTEN tumorsuppressor gene located at 10q22. Polyps arise more commonly fromectodermal rather than endodermalelements.
    • 80% of patients present with benign tumorof the hair shaft.CNS is the second most involved system,with approx 40% having macrocephaly.The majority of patients with Cowdensdisease suffer from benign thyroid or breastdisease- projected lifetime risk of 10% forthyroid cancer and of 30–50% for breastcancer.
    • Cowdens DiseaseAnnual physical exam with specialattention to thyroidMammography at age 30 or 5 yrbefore earliest breast cancer case inthe family
    • 6.Hyperplastic polyposis syndromeHyperplastic polyps are found commonly inthe large bowel, predominantly in the rectumand sigmoid.Because of their small size, hyperplasticpolyps rarely cause symptoms.However, large or multiple hyperplastic polypsoccasionally can be responsible forgastrointestinal symptoms.
    • HPS is a rare conditionCharacterized by numerous hyperplasticpolyps throughout the large bowel that givethe mucosa a "studded" look.The endoscopic and radiologic appearanceof the mucosal abnormalities closelyresembles FAP, but hyperplastic polyposisis not heritable and does not have anyextraintestinal manifestations.
    • 7.Hereditary mixed polyposissyndromeMode of inheritance is unknown.The syndrome is characterized by atypical juvenilepolyps, polyps containing mixed histology, ormultiple polyps of more than one histologic type inan individual.Neurofibromatosis type 1 (NF1)Individuals with NF1 may exhibit multipleintestinal polypoid neurofibromas organglioneuromas in the small bowel, stomach, andcolon
    • 7.Cronkite-Canada syndrome Characterized by diffuse hamartomatouspolyposis The polyps are Ectodermal abnormalities suchas alopecia, onychodystrophy, and skinhyperpigmentation. The syndrome can be distinguished by thediffuse distribution of polyps throughout theentire gastrointestinal tract with exception ofthe esophagus, which is spared.
    • Symptoms include diarrhea, weight loss, nausea,vomiting, and anorexia, as well as paresthesias,seizures, and tetany related to electrolyteabnormalities.Cancer occurs in the stomach, colon, and rectum, butit remains controversial whether polyps in Cronkite-Canada syndrome possess malignant potential.As many as 15% of patients with Cronkite-Canadasyndrome have a malignant tumor at the time ofdiagnosis
    • Five-year mortality rates as high as 55percent have been reported with mostdeaths due to gastrointestinal bleeding,sepsis, and congestive heart failure.Treatment has included nutritionalsupport, corticosteroids, acid suppression,and antibiotics
    • 8.Bannayan-Riley-Ruvalcaba SyndromeRare autosomal dominant conditionIncludes two other syndromes, both of which, likeCowdens disease, are associated with geneticalterations in the PTEN gene on chromosome 10q23 ,may be considered a variant of juvenile polyposis coli.No increased risk of colorectal carcinoma, othergastrointestinal malignancies, or extraintestinalmalignancy has been documented in these patients.
    • It is characterized by hamartomatous polyps of the gastrointestinal tract macrocephaly mental retardation,delayed psychomotor development lipid storage myopathy,Hashimotos thyroiditis,hyperpigmentation of the skin of the penis.
    • Research testing of PTEN geneavailable No known publishedrecommendations for screening
    • Gorlin syndrome (GS), Also termed nevoid basal cell carcinoma syndrome commonly presents with Hamartomatous gastric polyps, Palmar pits, Short metacarpals, Odontogenic keratocysts, Intracranial calcifications, Skeletal malformations, Neoplasia (basal cellcarcinoma, ovarian carcinoma, medulloblastoma). (GS) may present in infancy with congenital hydrocephalus, cleft lip and palate, lungcysts, rib and vertebral anomalies, and palmar pits. Children with GS may present with symptoms of medulloblastoma when youngerthan 5 years. Dental anomalies and basal cell carcinoma can appear in adolescents.
    •  Patients with GS may require surgicalmanagement for the following: Craniofacial lesions (cleft lip and palate, jaw cysts,other mandibular lesions) Abdominal masses (mesenteric cysts, lymphaticcysts, ovarian fibromas) Diagnostic and therapeutic interventions forpotential neoplasia within the CNS(medulloblastoma), skin (basal cell carcinoma),jaw (fibrosarcoma), ovaries (fibrosarcoma), andendometrium (adenocarcinoma)