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.
POLYPS WITH LARGER MASS HAVEGREATER VOLUME OF NEOPLASTICCELLS ,HENCE A HIGHERLIKELIYHOOD OF HARBORINGCANCER.POLYP SIZE(mm)<56-1516-2516-3637-42>42NUMBER513735811069516219677% WITH INVASIVECARCINOMA02.218.642.863.978.9
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.
Adenomatous polyps:Are commonThese 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)Tubulovillous10%-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 dischargeCan harbor carcinoma in situ or invasivecarcinoma more frequently than otheradenomas.
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.
Advanced pathologic risk factorsAdenomatous polyps >1 cm in diameterAdenomatous polyps with high-gradedysplasiaAdenomatous polyps with >25 percentvillous histology
Adenoma carcinomasequencePeak 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 thirdSm2: invasion into middle thirdSm3:invasion into lower third.
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 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
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.
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 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.
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.
Mandibular osteoma in apatient with Gardnerssyndrome.Radiograph of a mandibledemonstrating mandibularosteoma.
Turcot syndromeIncludes polypsMedulloblastomaCongenitalhypertrophy of theretinal pigmentedepithelium[CHRPE]Glioblastomamultiforme.
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.
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.
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 bowelOnce FAP has been diagnosed, the aim is toperform prophylactic surgeryPatients 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 anastamosisProctocolectomy 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 ofCutaneous cystsSymptomatic dental anomalies and osteomasBiopsy and resection for malignancies, includinghepatoblastoma, thyroid carcinoma, osteocarcinoma,gastric carcinoma, periampullary carcinoma, and biliarytract carcinomaLiver transplantation may be required in patients withhepatoblastomaPatients with Turcot syndrome requiresurgical intervention for diagnosis and management ofCNS lesions, gastric lesions and hepatic lesions.
Postop surveillanceAfter IRA, the retained rectum should be examinedusing a flexible sigmoidoscope, every 6–12 months.Polyps larger than 5 mm should be removedIf 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.
ChemopreventionHave 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 syndromeAutosomal dominant. It also known as Lynch I and II syndromes.The Lynch I variants describe patients withpredominantly colorectal cancer at a young ageLynch II: those with both colorectal andextracolonic cancers.
Accounts for 3–5% of all colorectal cancers withpredominance of mucinous or poorly differentiated(signet cell) adenocarcinomaDespite 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
MANAGEMENTWhen 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 syndromeThe combination ofhamartomatous polyps of theintestinal tractGermline 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 GynecomastiaThe 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.
Peutz-Jeghers Syndrome surveillanceUpper 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 syndromeInherited 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 screeningScreening by age 12 yr if symptoms havenot yet arisenColonoscopy with multiple randombiopsies every several years
5.Cowden syndrome Also known as multiple hamartoma-neoplasia syndrome.It is an autosomal dominant conditionComplete 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 DiseaseAnnual physical exam with specialattention to thyroidMammography at age 30 or 5 yrbefore earliest breast cancer case inthe family
6.Hyperplastic polyposis syndromeHyperplastic 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 conditionCharacterized 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 polyposissyndromeMode 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 SyndromeRare autosomal dominant conditionIncludes 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)