Polyps and Polyposis

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    Colorectal polyps and

    polyposis syndromes

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    Colorectal polyps

    • visible protrusion

    above the surface of

    the surrounding

    normal large bowel

    mucosa

    • Detected by

    endoscopy or by DCBE

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    Classication of colorectalpolyps

    Histologicalclassication

    Polyp type Malignant potential

    on!neoplastic Hyperplastic o

    Hamartomatous

    "#uvenile$ Peut%!&eghers'

    (ymphoid

    )n*ammatory

    eoplastic "adenoma' +ubular adenoma",!-./ villous tissue'

     0es

     +ubulovillousadenoma

    "-.!1./ villous tissue'

    2illous adenoma"1.!3,,/ villous tissue'

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    Hyperplastic polyps

    • Ma#ority of non!neoplastic polyps

    • Prevalence rates of -,!45/ "autopsy

    and screening colonoscopy studies'

    • Predominantly located in the distal

    colon and rectum

    • 6enerally small "7,8.cm' in si%e

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    9denomas : facts andgures

    • 1,/ of all colorectal polyps

    • )ncrease with age "44/ of population by .,yr$ and in .,/ by 1,yr'

    • 1,/ located in the left colon

    • 1,/ are solitary "4,/ synchronous'

    • 1,/ are small "73cm in si%e'

    • 1/ have severe dysplasia$ 4!./ have invasive cancer

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    9denoma!carcinomase;uence

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    =actors determining ris> of malignanttransformation within adenomas

    High ris> (ow ris>

    (arge si%e " ?38.cm' @mall si%e " 73cm'

    @essile or *at Pedunculated

    @evere dysplasia Mild dysplasia

    2illous architecture +ubular architecture

    Polyposis syndrome "multiple polyps' @ingle polyp

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    Percent of adenomas containinginvasive cancer by si%e and histology

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    Malignant colorectal polyp

    • Polyp that contains invasive cancer

    • Malignant cells that have invadedthrough the mucularis mucosa into the

    submucosa

    mm

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    Management of colorectal polyps "3'

    =actors

    Location: colon or rectum

    Morphology: pedunculated or sessile

    Histology: benign or malignant

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    Management of colorectal polyps "-'

    EAcision

    Pedunculated

    Colonoscopic polypectomy usually possible

    @essile

    Colonoscopic polypectomy if possible "larger polyps may re;uire piecemeal removal'

    Endoscopic removable not possible  operative removal

    • Colon colectomy

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    Management of colorectal polyps "4'

    Denitive MA "histology'

    Benign

    @urveillance

    colonoscopy

    Malignant

    Depends onhistological

    characteristics

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    @urveillance after polypectomyBenign polyps

    Characteristics of polypseAt =

    colonoscopy

    small rectal hyperplasic polyps "Faverage ris>' 3, years

    one or two small "73cm' tubular adenomas .!3, years

    4 to 3, adenomas$ or adenoma G 3cm$ or villous features$ or

    high!grade dysplasia4 years

    ?3, adenomas 74 years

    sessile adenomas removed piecemeal -! months

    6uidelines for colonoscopy surveillance after polypectomy a consensus

    update by the @ Multi!@ociety +as> =orce on Colorectal Cancer and the

    9merican Cancer @ociet -,,

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    Malignant Polyp=actors determining need of radical

    surgeryHistology

    • Poorly diIerentiated

    • Margin 7-mm

    • @tal> invasion

    • (ymphovascular invasion

    )ncrease ris> of recurrence and ( -o

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    =amilial Colorectal Cancer

    @yndromes

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    =amilial adenomatous polyposis"=9P'

    • 3/ of all C

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    =9P

    • ?3,, adenomas

    • Patients develop adenomas

    by the mean age of 3

    years$ and Ces -,!4, years to

    develop C

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    Molecular genetics of =9P

    • Caused by mutations of 9PC gene "tumour suppressor gene' on chromosome

    .;-3

    • Encodes for a protein$ which functions in cell adhesion and signal transduction

    • Mutations will result in truncated protein and aIect cell growth

    9PC t >

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    9PC as gate>eeper geneadenoma!carcinoma

    se;uence

    Loeb 1991

    Mechanisms of Carcinogenesis

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    Mechanisms of Carcinogenesisin =9P

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    6enotype vs8 phenotype

     ClinicalPresentation

    Extracolonic

    manifestations

     Affected part of gene

    Cell adhesion and structural

    molecules

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    EAtracolonic manifestations

    • Congenital hypertrophy of retinalpigmented epithelium "CH

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    6ardnerLs syndrome

    Desmoid

    Chest broma

    Mandibular osteoma @>ull osteoma

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    9ttenuated =9P "9=9P'

    • 2ariant of =9P

    • 73,, adenomas

    • (ate age!of!onset  "adenomas at 55 C

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    Cancer ris>s in =9P

    Cancer Cancer ris>s

    Colon Near 100%

    Duodenal or periampullary .!3,/

    Pancreatic 9bout -/

     +hyroid 9bout -/

    6astric 9bout ,8./

    C@$ usually cerebellarmedulloblastoma "+urcotOs

    syndrome'73/

    Hepatoblastoma 38/ of children 7. years of age

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    Diagnosis of =9P

    Mutation 

    Protein truncation test

    D9 se;uencing

    6enetic testsEndoscopy

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    @creening of =9P

    • Genetic screening  of family members for 9PC mutations

    •  Annual fexible sigmoioscopy  beginning at age 3,!3-

    until age 5,$ then every 4!. years

    !"# polyposis is present$ colectomy shoul be consiere

    • G& every 3!4 years is also recommended to evaluate

    for upper 6) adenomas

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    Prophylactic colectomy for=9P

    •  +he aim of surgical treatment of =9P is to

    intervene in the adenoma!carcinoma se;uence by

    removing the adenomas before the

    transformation to malignancy occurs

    =9P C

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     +iming of surgery

    Clinical presentation +iming of surgery

    9symptomatic patient with

    modest number of small

    adenomas

    9ble to wait for a few years for

    surgery$ as long as colonoscopic

    surveillance is performed yearly

    @ymptomatic patient with large

    number of adenomasEarly surgery

    @uspicious of C

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    @tandard surgical treatment

    'estorati(e proctocolectomy )ith ileal pouch*analanastomosis

    @uitable for most patients with=9P

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    ther surgical options

    +otal colectomy )ith ileorectal

    anastomosis ,"'A-.roctocolectomy )ith ileostomy 

    9ttenuated =9P

    low rectal cancers

    poor sphincters

    Desmoid tumors

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    Medical treatment of =9P• @ulindac "@9)D' and celecoAib "CQ!- inhibitor' shown to

    control and reduce the number of colorectal adenomas in =9P

    • ot denitive treatment

    •  +empori%ing treatment "eg when surgery needs to be delayed'

    • May control pouch and rectal polyposis after initial

    prophylactic surgery

    Hereditary nonpolyposis

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    Hereditary nonpolyposiscolorectal cancer "HPCC'

    Dr8 98 @8 Rarthin and the rst

    HPCC pedigree$ Sthe family

    6L 3JK.

    Dr8 Henry (ynch rst described the term

    Scancer family syndromeL in 3K "later

    renamed as (ynch syndrome and

    HPCC'

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    HPCC

    • -!./ of all Ces only 4!. years todevelop C

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    HPCC (ynch syndromes

    (ynch syndrome ) (ynch syndrome ))

    Early onset of C

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    HPCC related eAtracolonictumors

    Endometrial cancer is the most common eAtracolonic malignancy

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    Diagnosis 9msterdamcriteria 3

    Due to lac> of phenotypic mar>ers li>e polyps

    Diagnosis is based on family history of C

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    Diagnosis 9msterdamcriteria -

    Same as Amsterdam 1 but

    includes all HNPCC

    related tumors

    Molecular genetics of

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    Molecular genetics ofHPCC

    HPCC is caused by mutations of  

    &NA mismatch repair ,MM'- genes

    Survey NA forreplication errors

    Molecular genetics of

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    Molecular genetics ofHPCC

    • Mutations of these MM< genes will result in replication errors during

    D9 synthesis ,microsatellite instability- leading to  acceleration o#

    genetic mutations

    • HPCC patients develop adenomas at the same rate as the general

    population

    • nce these adenomas develop$ however$ defective D9 repair ensues

    and mismatches accumulates

    •  +hus$ it ta>es only 4!. years to develop C

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    Molecular genetics ofHPCC

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    Demonstration of M@)

    MicrosatelliteMar>ers

    9mplify by Polymerase Chain

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    M@@ +umor

    D2S123D17S250BAT 25BAT 26

    D5S346

    NORMA

    L

    MUCOS

    A

    TUMOR

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    M@) +umor

    NORMA

    L

    TUMOR

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    Microsatellite

    instability testing

    egative

    @top

    )mmunohistochemistry

    M(H3

    M@H-@e;uence M(H3 o protein

    @e;uence M@H- o protein

    ormal

    @top

    Positive

    HPCCMutation detection for M(H3 and M@H-

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    @creening of HPCC

    • Colonoscopy every - years starting at ages -,!-.

    or

    . years younger than the earliest diagnosis of C

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    @urgical treatment ofHPCC

    •  +otal colectomy with ileorectal anastomosis

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    Hamartomatous polyposissyndromes

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    Peut%!&eghers syndrome

    • )ncidence 3 in -,,$,,, persons

    9utosomal dominant

    • Mutations of the @+U33 gene onchromosome 3K

    • Characteri%ed by perioral

     pigmentations and hamartomatous polyps throughout the 6) tract

    • G" an non*G" cancers are common

    @ite of polyps =re;uency

    @tomach 4J/

    @mall bowel 1J/

    Colon 5-/

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    Cancer ris> in P!& syndrome

    6) cancers Cancer ris>s

    Colon 4K/

    Pancreatic 4/

    @tomach -K/

    @mall bowel 34/

    Esophagus ,8./on!6) cancers Cancer ris>s

    Breast .5/

    varian -3/

    terine K/

    @eA cord tumour with annular tubules"@C+9+' -,/ become malignant

    @ertoli cell tumour 3,!-,/ become malignant

    (ung 3./

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     &uvenile polyposis

    • Presence of ≥3, #uvenile polyps in

    the 6) tract

    • )ncidence 3 in 3,,$,,, persons

    • 9utosomal dominant

    • Mutation of @M9D5 gene on

    chromosome 3J

    • Polyps are most commonly found

    in colon

    • Colon cancer ris> .,/

    • of gastric$ duodenal$ and

    pancreatic cancers

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