Colon TumoursColon Tumours

Cengiz Pata, M.DCengiz Pata, M.D

Gastroenterology Department, Yeditepe Gastroenterology Department, Yeditepe UniversityUniversity

IstanbulIstanbul

“ “ Colon TumoursColon Tumours””                                

Benign%.....Benign%.....MalignMalign

Pathogenesis of ProgressionPathogenesis of Progression from Adenoma to Carcinoma from Adenoma to Carcinoma

AdenomaAdenoma Neoplastic transformationNeoplastic transformationof one cell !of one cell !

MutationMutation APC, DCC, k, RASAPC, DCC, k, RAS

DeletionDeletion 5q, 17b5q, 17b

ActivationActivation c, mycc, myc MILD MILD MODERATE MODERATE SEVERE DYSPLASIA SEVERE DYSPLASIA

> > 2 cm – Villous components 2 cm – Villous components MalignancyMalignancy

Road of carcinomaRoad of carcinoma

Benign Benign TumoursTumours

= POLYPS (mostly) = POLYPS (mostly)

but may be malign !but may be malign !

Mucosal protrusions (= projections) Mucosal protrusions (= projections)

into the lumen of the GI – tract.into the lumen of the GI – tract.

Premalign disease of Premalign disease of the colonthe colon

PolypsPolyps Hereditary and nonhereditary Hereditary and nonhereditary

polyposis syndromepolyposis syndrome Hereditary nonpolyposis Hereditary nonpolyposis

syndromesyndrome İnflamatuar bowel diseaseİnflamatuar bowel disease

The Polyposis Syndrom’sThe Polyposis Syndrom’s

  Rarely singleRarely single

  Often multipleOften multiple

> 100 Polyps = Polyposis> 100 Polyps = Polyposis

ClassificationClassification“ There is no unique classification ““ There is no unique classification “

A.A. FORMFORM

B.B. SIZESIZE

C.C. HISTOLOGYHISTOLOGY

D.D. DYSPLASIA (Degree !)DYSPLASIA (Degree !)

E.E. Hereditary X Non-hereditaryHereditary X Non-hereditary

F.F. NEOPLASTIC X NON-NEOPLASTICNEOPLASTIC X NON-NEOPLASTIC

FORMFORM

Sessile (broad based)Sessile (broad based)

Pedunculated (stalk)Pedunculated (stalk)

Semi-pedunculatedSemi-pedunculated

SIZE SIZE + (correlation to Ca-Risk)+ (correlation to Ca-Risk)

<< 1 cm1 cm (( 1 - 2 %) 1 - 2 %)

1-2 cm1-2 cm (( 10 %) 10 %)

>> 2 cm2 cm (( 40 - 50 %) 40 - 50 %)

HISTOLOGYHISTOLOGY

Tubular Tubular : inf. > 75 % in Histology : inf. > 75 % in Histology

is from a complex is from a complex

network of branching network of branching

adenomatous adenomatous architecturearchitecture VillousVillous : > 75 % : > 75 % in Histology in Histology

ffront like surfaceront like surface Tubulo-villousTubulo-villous : : 50 : 5050 : 50 % %

(not easy to distinguish)(not easy to distinguish)

Tubulo-adenomaTubulo-adenoma

DYSPLASIA (= DEGREE)DYSPLASIA (= DEGREE)

Mild:Mild: 5 % 5 %

Moderate: Moderate: 20 20%%

Severe: > 30 %Severe: > 30 %

Polyposis SyndromePolyposis Syndrome

HereditaryHereditary FAPFAP

  Gardner SyndromeGardner Syndrome

  Turcot SyndromeTurcot Syndrome   PEUTZ-JEGHERS PEUTZ-JEGHERS

SyndromeSyndrome JUVENILE (Fam) JUVENILE (Fam)

POLYPOSİSPOLYPOSİS COWDEN SyndromeCOWDEN Syndrome

Non-hereditaryNon-hereditary

   CRONKHITE – CRONKHITE –

CANADA SyndromeCANADA Syndrome

HYPERPLASTIC (= HYPERPLASTIC (=

METAPLASTIC)METAPLASTIC)

INFLAMMATORYINFLAMMATORY

EASY – SIMPLIFIED EASY – SIMPLIFIED CLASSIFICATIONCLASSIFICATION

NEOPLASTICNEOPLASTIC

AdenomasAdenomas

CarcinomasCarcinomas

NON-NEOPLASTICNON-NEOPLASTIC

HamartomatousHamartomatous HyperplasticHyperplastic JuvenileJuvenile InflammatoryInflammatory

MMoreore Simplified Simplified ClassificationClassification

            Four main typesFour main types

A ) AdenomasA ) Adenomas

B ) HamartomatousB ) Hamartomatous

C ) HyperplasticC ) Hyperplastic

D ) InflammatoryD ) Inflammatory

                Rare TypesRare Types

LipomaLipoma

FibromaFibroma

NeurofibromaNeurofibroma

LeiomyomaLeiomyoma

Nodular Lymphoid Nodular Lymphoid

HyperplasiaHyperplasia

SymptomsSymptoms

Most cases are asymptomaticMost cases are asymptomatic

Bleeding (increases with increased Bleeding (increases with increased

polyp size)polyp size) Abdominal discomfort (rare)Abdominal discomfort (rare)

ObstructionObstruction

DiagnosisDiagnosis

Barium-studiesBarium-studies

Endoscopically (Endoscopy is Endoscopically (Endoscopy is

preferredpreferred

polypectomypolypectomy

histologic examinationhistologic examination

Hereditary Polyposis Hereditary Polyposis SyndromesSyndromes

 

TYP LOCATION GENETICS

HISTO ASSOC.FINDINGS

Ca-Risk

           

Familial Juvenile Polyposis

Colonrectum AD Ham. ( - )

8-10 %

           

Peutz-Jeghers Syndrome

Stomach, small bowel

AD Ham. Pigmentation

2-3%

  Colon        

           

FamilialAdenoma-tous Polyposis

Stomach Colonrectum

AD Adenoma CHRP> 90 %

         

TYPES OF FAPTYPES OF FAP

GARDNER S.GARDNER S. + Osteoma, Fibroma, + Osteoma, Fibroma,

Lipoma +Epidermoid-cystsLipoma +Epidermoid-cysts

TURCOT S.TURCOT S. + Glio-, and Medulloblastoma+ Glio-, and Medulloblastoma

AAPLAAPL (= before hereditary flat (= before hereditary flat

Adenomas) = Adenomas) =

(Attenuated Adenomatous P.)(Attenuated Adenomatous P.)

High Grade Dysplasia High Grade Dysplasia 5. Deka 5. Deka

Ca Risk > 100% !Ca Risk > 100% !

FAP ve Gardner SFAP ve Gardner S

Peutz-Jeghers SyndromePeutz-Jeghers Syndrome

Recent findingsRecent findings

GITGIT ++PigmentationPigmentation MouthMouth

HandsHands

FeetFeet

Tumours :Tumours : ovarianovarian

testistestis

Peutz Jeghers S.Peutz Jeghers S.

Peutz Jeghers S.Peutz Jeghers S.

CCronkhite-ronkhite-CCanada anada SyndromeSyndrome

Acquired, nonfamilialAcquired, nonfamilial Middle aged adultsMiddle aged adults Hamartomas + AdenomasHamartomas + Adenomas Stomach, small bowel, colonStomach, small bowel, colon Associated findings :Associated findings : Alopecia Alopecia

cutaneous pigmentation cutaneous pigmentation dystrophic nails dystrophic nails

DiarrhoeaDiarrhoea Weight lossWeight loss Abdominal painAbdominal pain

Ca-RiskCa-Risk 5%5%

MANAGEMENTMANAGEMENT

Colorectal polypColorectal polyp

Tubular orTubular or VillousVillous OtherOther

TubulovillousTubulovillous < 1 cm< 1 cm > 1 cm> 1 cm no no

investigationinvestigation

< 5 polyps < 5 polyps > 5 polyps> 5 polyps

in totalin total Repeat in 1 yearRepeat in 1 year

Repeat in 3 yearsRepeat in 3 years

All clearAll clear Repeat in 5 yearsRepeat in 5 years

PolypectomyPolypectomy

SizeSize < 1 cm< 1 cm

< 2-3 cm< 2-3 cm

Total < 5 polypsTotal < 5 polyps

OperationOperationSize >3-5 cmSize >3-5 cm

FAP :FAP : Prophylactic Colectomy !Prophylactic Colectomy !

Colorectal CancerColorectal Cancer

POLYP POLYP DYSPLASIA DYSPLASIA CANCER CANCER

sequencesequence

is now generally acceptedis now generally accepted

Colorectal CancerColorectal Cancer

– Second most common Second most common cancer in USA , Germany, cancer in USA , Germany, UK, France !UK, France !

– After age 40 to age 80 the After age 40 to age 80 the incidence doubles !!!incidence doubles !!!

Colon Ca Colon Ca

RISC FACTORSRISC FACTORS

Low-fiber, high fat dietLow-fiber, high fat diet Age > 40Age > 40 Personal History : Colorectal adenomasPersonal History : Colorectal adenomas Family History : Polyps SyndromesFamily History : Polyps Syndromes Inflammatory Bowel Disease ( CD, UC)Inflammatory Bowel Disease ( CD, UC) Genital tract cancer in womenGenital tract cancer in women Lynch Syndrome : Hereditary Lynch Syndrome : Hereditary

NonpolyposeNonpolypose Colon Carcinoma (HNPCC)Colon Carcinoma (HNPCC)

Lynch Syndrome :Lynch Syndrome : Hereditary Nonpolyposis Hereditary NonpolyposisColon Carcinoma (HNPCC)Colon Carcinoma (HNPCC)

Autosomal dominantAutosomal dominant

Amsterdam criteria:3,2,1 rulesAmsterdam criteria:3,2,1 rules

(3 relative, 2 generation,1 person<50(3 relative, 2 generation,1 person<50

DNA mismatch repairDNA mismatch repair

6% of colorectal carcinoma6% of colorectal carcinoma

Typ 2:Endometrium, stomach, hepatobiliary CaTyp 2:Endometrium, stomach, hepatobiliary Ca

HMSA %60 (+)HMSA %60 (+)

SymptomsSymptoms

Bleeding (Gross or occult)Bleeding (Gross or occult)

Change in bowel habit ; constipation, Change in bowel habit ; constipation,

diarrhoea, decreased caliber of stooldiarrhoea, decreased caliber of stool

AnemiaAnemia

Weight lossWeight loss

AnorexiaAnorexia

Classification/LocalizationClassification/Localization

RectumRectum 60%60%

SigmaSigma 20%20%

Rest colonRest colon 20%20%

Most Common Most Common PresentationPresentation

Left sided :Left sided : BleedingBleeding

ObstructionObstruction

DiarrhoeaDiarrhoea

Right sided :Right sided : FatiqueFatique

WeaknessWeakness

Occult blood lossOccult blood loss

Obstruction (late)Obstruction (late)

Staging - SystemsStaging - Systems

TNM :TNM : Tumor / Nodes / MetastasisTumor / Nodes / Metastasis

UICC :UICC : Union Internationale Contra Le Union Internationale Contra Le CancerCancer

ASTLER-COLLER :ASTLER-COLLER : DEPTH OF İNVASİONDEPTH OF İNVASİON

DUKEDUKE ++

Lymph node Lymph node metastasismetastasis

00 TT1s1s N Noo M Moo Carcinoma in situ (Basal Carcinoma in situ (Basal membrane intact)membrane intact)

I aI a Dukes ADukes A TT11 N Noo M Moo Tumor involves Tumor involves mucosa+submucosamucosa+submucosa

I bI b TT22 N Noo M Moo Tumor invades to Tumor invades to muscularis muscularis propriapropria (but not true it !!!) (but not true it !!!)

IIII Dukes Dukes B1B1

TT33NNoo M Moo Tumor penetrates Tumor penetrates through the through the bowel wallbowel wall

IIII Dukes Dukes B2B2

TT44 N Noo M Moo Tumor involves Tumor involves viscerales viscerales peritoneumperitoneum

IIIIII Dukes CDukes C TTanyany N N1-21-2 M Moo + Regional positive lymph + Regional positive lymph nodesnodes

IVIV Dukes DDukes D TTanyany N Nanyany M M11 Distant metastatic spreadDistant metastatic spread

Colon Ca-SurviColon Ca-Survi

Prognosis by DUKE’s Prognosis by DUKE’s StagingStaging

5 year survival rate :5 year survival rate :A :A : 80%80%

B1 :B1 : 65%65%

B2 :B2 : 43%43%

C1 :C1 : 53%53%

C2 :C2 : 15%15%

D :D : 0% 0%

Negative Prognostic Negative Prognostic FactorsFactors

High-grade tumorHigh-grade tumor

ObstructionObstruction

PerforationPerforation

Diagnostic Procedures Diagnostic Procedures and Presurgical and Presurgical EvaluationEvaluation

Detailed History Detailed History

(including family (including family

history)history)

Physical examination Physical examination

(including (including

breast+pelvicbreast+pelvic

ovary+endometrium)ovary+endometrium)

Laboratory : Laboratory :

CEA, CA 19-9CEA, CA 19-9

TBC, Liver TBC, Liver

profileprofile

ColonoscopyColonoscopy

RadiographsRadiographs

TherapyTherapy

For cure in Duke’s For cure in Duke’s A, B, CA, B, C

For palliation in Duke’sFor palliation in Duke’s DD

SurgicalSurgical

Adjuvant Chemotherapy Adjuvant Chemotherapy ( 5-FU / Folinasid)( 5-FU / Folinasid)

Palliative ( Stenosis Palliative ( Stenosis anus-praeterminalis)anus-praeterminalis)

SURGİCALSURGİCAL

Radical tumor-resection Radical tumor-resection

+ regional lymph node extripation+ regional lymph node extripation

ColonColon HemicolectomyHemicolectomy

SigmaSigma

TransversumTransversum > > resectionresection

RectumRectum Distance “Linea ANOCUTANEA “Distance “Linea ANOCUTANEA “ cure + maintanencecure + maintanence of fecal of fecal

continencecontinence

SCREENING of PatientsSCREENING of Patients

After age 40 annual rectal examinationAfter age 40 annual rectal examination

Annual fecal occult blood testAnnual fecal occult blood test every year after every year after

age 50age 50

After age 50 Sigmoidoscopy every 5 yearsAfter age 50 Sigmoidoscopy every 5 years, ,

colonoscopy every ten yearscolonoscopy every ten years

Today: colonoscopy every 5 year after 50 Today: colonoscopy every 5 year after 50

yearsyears

Follow up in patients with Follow up in patients with positive family historypositive family history

HNPCC’ da İzlemHNPCC’ da İzlem

Ulcerative colitis Ulcerative colitis followingfollowing