Ca Co|orecta|

Colon and recLal cancer lncldence was negllglble before 1900 1he lncldence of colorecLal cancer has been rlslng
dramaLlcally followlng economlc developmenL and lndusLrlallzaLlon CurrenLly colorecLal cancer ls Lhe Lhlrd leadlng
cause of cancer deaLhs ln boLh males and females ln Lhe unlLed SLaLes
12


Adenocarclnomas comprlse Lhe vasL ma[orlLy (98) of colon and recLal cancers CLher rare recLal cancers lncludlng
carclnold (04) lymphoma (13) and sarcoma (03) are noL dlscussed ln Lhls arLlcle Squamous cell carclnomas
may develop ln Lhe LranslLlon area from Lhe recLum Lo Lhe anal verge and are consldered anal carclnomas very rare
cases of squamous cell carclnoma of Lhe recLum have been reporLed
13


ApproxlmaLely 20 of colon cancers develop ln Lhe cecum anoLher 20 ln Lhe recLum and an addlLlonal 10 ln Lhe
recLoslgmold [uncLlon ApproxlmaLely 23 of colon cancers develop ln Lhe slgmold colon
1


1he lncldence and epldemlology eLlology paLhogenesls and screenlng recommendaLlons are common Lo boLh colon
cancer and recLal cancer 1hese areas are addressed LogeLher

athophys|o|ogy
1he mucosa ln Lhe large lnLesLlne regeneraLes approxlmaLely every 6 days CrypL cells mlgraLe from Lhe base of Lhe
crypL Lo Lhe surface where Lhey undergo dlfferenLlaLlon and maLuraLlon and ulLlmaLely lose Lhe ablllLy Lo repllcaLe

1he slgnlflcanL porLlons of colorecLal carclnomas are adenocarclnomas 1he adenomacarclnoma sequence ls well
descrlbed ln Lhe medlcal llLeraLure
14
Colonlc adenomas precede adenocarclnomas ApproxlmaLely 10 of adenomas
wlll evenLually develop lnLo adenocarclnomas 1hls process may Lake up Lo 10 years
1


1hree paLhways Lo colon and recLal carclnoma have been descrlbed
O Lhe adenomaLous polyposls coll (Alc) gene adenomacarclnoma paLhway
O Lhe heredlLary nonpolyposls colorecLal cancer (PnCC) paLhway
O ulceraLlve collLls dysplasla
1he Alc adenoma carclnoma paLhway lnvolves several geneLlc muLaLlons sLarLlng wlLh lnacLlvaLlon of Lhe Alc gene
whlch allows unchecked cellular repllcaLlon aL Lhe crypL surface WlLh Lhe lncrease ln cell dlvlslon furLher muLaLlons
occur resulLlng ln acLlvaLlon of Lhe ktos oncogene ln Lhe early sLages and p5J muLaLlons ln laLer sLages 1hese
cumulaLlve losses ln Lumor suppressor gene funcLlon prevenL apopLosls and prolong Lhe cells llfespan lndeflnlLely lf
Lhe Alc muLaLlon ls lnherlLed lL wlll resulL ln famlllal adenomaLous polyposls syndrome
PlsLologlcally adenomas are classlfled ln Lhree groups Lubular Lubulovlllous and vlllous adenomas ktos muLaLlons
and mlcrosaLelllLe lnsLablllLy have been ldenLlfled ln hyperplasLlc polyps 1herefore hyperplasLlc polyps may also have
mallgnanL poLenLlal ln varylng degrees
3


1he oLher common carclnogenlc paLhway lnvolves muLaLlon ln unA mlsmaLch repalr genes Many of Lhese mlsmaLched
repalr genes have been ldenLlfled lncludlng bMln1 bM5n2 blM51 blM52 and bM5n6 MuLaLlon ln mlsmaLched
repalr genes negaLlvely affecLs Lhe unA repalr 1hls repllcaLlon error ls found ln approxlmaLely 90 of PnCC and 13
of sporadlc colon and recLal cancers
16
A separaLe carclnogenlc paLhway ls also descrlbed ln lnflammaLory bowel
dlsease (l8u) Chronlc lnflammaLlon such as ln ulceraLlve collLls can resulL ln geneLlc alLeraLlons whlch Lhen lead lnLo
dysplasla and carclnoma formaLlon
1

requency
Un|ted States
Colon and recLal cancer ls Lhe Lhlrd mosL common cancer ln boLh females and males 1he Amerlcan Cancer SocleLy
esLlmaLes LhaL 106100 new cases of colon cancer and 40870 new cases of recLal cancer wlll occur ln 2009 73390
cases of colorecLal cancers are expecLed ln men and 71380 ln women
2
ApproxlmaLely 34090 deaLhs from colon
cancer and 17290 deaLhs from recLal cancer are expecLed Lo occur ln 2009

8oLh colon and recLal cancer lncldences as well as morLallLy raLes have been decreaslng for Lhe lasL Lwo decades from
663 per 100000 populaLlon ln 1983 Lo 464 ln 2003
2
1he raLe of decrease acceleraLed from 19982003 (Lo 28 per
year ln men and 22 per year ln women) ln parL because of lncreased screenlng allowlng Lhe deLecLlon and removal
of colorecLal polyps before Lhey progress Lo cancer 1he llfeLlme rlsk of developlng a colorecLal mallgnancy ls
approxlmaLely 6 ln Lhe general uS populaLlon 1hls decrease ls due Lo a decllnlng lncldence and lmprovemenLs ln boLh
early deLecLlon and LreaLmenL
nternat|ona|
AlLhough Lhe lncldence of colon and recLal cancer varles conslderably by counLry an esLlmaLed 944717 cases were
ldenLlfled worldwlde ln 2000 Plgh lncldences of colon and recLal cancer cases are ldenLlfled ln Lhe uS Canada !apan
parLs of Lurope new Zealand lsrael and AusLralla Low colorecLal cancer raLes are ldenLlfled ln Algerla and lndla 1he
ma[orlLy of colorecLal cancers sLlll occur ln lndusLrlallzed counLrles 8ecenL rlses ln colorecLal cancer lncldence have
been observed ln many parLs of Lhe !apan Chlna (Shanghal) and ln several LasLern Luropean counLrles
1

Morta||ty]Morb|d|ty
1he Amerlcan Cancer SocleLy esLlmaLes LhaL colorecLal cancer wlll accounL for 9 of all cancer deaLhs (49920) ln 2009
ln Lhe uS morLallLy raLes have been decreaslng ln boLh sexes for Lhe pasL 2 decades (1he 1 and 3year raLe for
paLlenLs wlLh colon and recLal cancer ls 83 and 64 respecLlvely) When colorecLal cancers are deLecLed early and
locallzed Lhe 3year survlval raLe ls 90
2

A revlew of 8 Lrlals by 8oLhwell eL al found allocaLlon Lo asplrln reduced deaLh caused by cancer lndlvldual paLlenL daLa
were avallable from 7 of Lhe 8 Lrlals 8eneflL was apparenL afLer 3 years of followup 1he 20year rlsk of cancer deaLh
was also lower ln Lhe asplrln group for all solld cancers A laLenL perlod of 3 years was observed before rlsk of deaLh was
decreased for esophageal pancreaLlc braln and lung cancers A more delayed laLenL perlod was observed for sLomach
colorecLal and prosLaLe cancer 8eneflL was only seen for adenocarclnomas ln lung and esophageal cancers 1he overall
effecL on 20year rlsk of cancer deaLh was greaLesL for adenocarclnomas
7

kace
1he lncldence of colorecLal cancer Lends Lo be hlgher ln WesLern naLlons Lhan ln Aslan and Afrlcan counLrles however
wlLhln Lhe unlLed SLaLes mlnor dlfferences ln lncldence exlsL among whlLes Afrlcan Amerlcans and Aslan Amerlcans
llveyear survlval raLes are lower among blacks (33) Lhan whlLes (66) Among rellglous denomlnaLlons colorecLal
cancer occurs more frequenLly ln Lhe !ewlsh populaLlon
2

Sex
1he lncldence of colorecLal mallgnancy ls sllghLly hlgher ln males Lhan ln females 1he overall agesLandardlzed
lncldence of colorecLal cancer was 63/100000 for males and 47/100000 for females beLween 1993 and 1999 1he
malefemale raLlo ls 137 MorLallLy raLes for colorecLal cancer were also hlgher ln males (234 per 100000) Lhan ln
females (18 per 100000) ln 1999 LefL colon carclnomas were more llkely Lo be observed ln males and rlghL colon
carclnomas were more llkely Lo be observed ln females
2

Age
1he lncldence of colorecLal cancer sLarLs Lo lncrease afLer age 33 and rlses rapldly afLer age 30 peaklng ln Lhe sevenLh
decade More Lhan 90 of colon cancers occur afLer age 30 Powever cases have been reporLed ln young chlldren and
adolescenLs
1

C||n|ca|
n|story
All paLlenLs should undergo a compleLe hlsLory (lncludlng a famlly hlsLory) and assessmenL of rlsk facLors for Lhe
developmenL of recLal cancer Many recLal cancers produce no sympLoms and are dlscovered durlng dlglLal or
procLoscoplc screenlng examlnaLlons

8leedlng ls Lhe mosL common sympLom of recLal cancer occurrlng ln 60 of paLlenLs 8leedlng ofLen ls aLLrlbuLed Lo
oLher causes (eg hemorrholds) especlally lf Lhe paLlenL has a hlsLory of oLher recLal problems rofuse bleedlng and
anemla are rare 8leedlng may be accompanled by Lhe passage of mucus whlch warranLs furLher lnvesLlgaLlon

Change ln bowel hablLs ls presenL ln 43 of paLlenLs change ls noL evldenL ln some cases because Lhe capaclLy of a
recLal reservolr can mask Lhe presence of small leslons When change does occur lL ls ofLen ln Lhe form of dlarrhea
parLlcularly lf Lhe Lumor has a large vlllous componenL 1hese paLlenLs may have hypokalemla as shown ln laboraLory
sLudles Some paLlenLs experlence a change ln Lhe callber of Lhe sLool Large Lumors can cause obsLrucLlve sympLoms
1umors locaLed low ln Lhe recLum can cause a feellng of lncompleLe evacuaLlon and Lenesmus

CcculL bleedlng ls deLecLed vla a fecal occulL blood LesL (lC81) ln 26 of all cases Abdomlnal paln ls presenL ln 20 of
Lhe cases arLlal largebowel obsLrucLlon may cause collcky abdomlnal paln and bloaLlng 8ack paln ls usually a laLe slgn
caused by a Lumor lnvadlng or compresslng nerve Lrunks urlnary sympLoms may also occur lf Lhe Lumor ls lnvadlng or
compresslng Lhe bladder or prosLaLe

Malalse ls a nonspeclflc sympLom and presenL ln 9 of recLal cancer cases 8owel obsLrucLlon due Lo a hlghgrade recLal
leslon ls rare occurrlng ln 9 of all cases elvlc paln ls a laLe sympLom usually lndlcaLlng nerve Lrunk lnvolvemenL and
ls presenL ln 3 of all cases CLher manlfesLaLlons lnclude emergencles such as perlLonlLls from perforaLlon (3) or
[aundlce whlch may occur wlLh llver meLasLases (1)
hys|ca|
hyslcal examlnaLlon ls performed wlLh speclflc aLLenLlon Lo slze and locaLlon of recLal cancer ln addlLlon Lo posslble
meLasLaLlc leslons lncludlng enlarged lymph nodes or hepaLomegaly 1he remalnder of Lhe colon ls also evaluaLed

ulglLal recLal examlnaLlon (u8L) provldes an opporLunlLy Lo readlly deLecL abnormal leslons 1he average flnger can
reach approxlmaLely 8 cm above Lhe denLaLe llne 8ecLal Lumors can be assessed for slze ulceraLlon and presence of
any pararecLal lymph nodes llxaLlon of Lhe Lumor Lo surroundlng sLrucLures (eg sphlncLers prosLaLe vaglna coccyx
and sacrum) also can be assessed u8L also permlLs a cursory evaluaLlon of Lhe paLlenLs sphlncLer funcLlon 1hls
lnformaLlon ls necessary when deLermlnlng wheLher a paLlenL ls a candldaLe for a sphlncLersparlng procedure 8lgld
procLoscopy ls also performed Lo ldenLlfy Lhe exacL locaLlon of Lhe Lumor ln relaLlon Lo Lhe sphlncLer mechanlsm
Causes
1he eLlology of colorecLal cancer ls unknown buL colorecLal cancer appears Lo be mulLlfacLorlal ln orlgln and lncludes
envlronmenLal facLors and a geneLlc componenL uleL may have an eLlologlc role especlally dleL wlLh hlgh faL conLenL
ApproxlmaLely 73 of colorecLal cancers are sporadlc and develop ln people wlLh no speclflc rlsk facLors 1he remalnlng
23 of cases occur ln people wlLh slgnlflcanL rlsk facLorsmosL commonly a famlly hlsLory or personal hlsLory of
colorecLal cancer or polyps whlch are presenL ln 1320 of all cases CLher slgnlflcanL rlsk facLors are cerLaln geneLlc
predlsposlLlons such as heredlLary nonpolyposls colorecLal cancer (PnCC 47 of all cases) and famlllal adenomaLous
polyposls (lA 1) and lnflammaLory bowel dlsease (l8u 1 of all cases)
Lnv|ronmenta| actors
D|et

A hlghfaL lowflber dleL ls lmpllcaLed ln Lhe developmenL of colorecLal cancer Speclflcally people who lngesL a dleL
hlgh ln unsaLuraLed anlmal faLs and hlghly saLuraLed vegeLable olls (eg corn safflower) have a hlgher lncldence of
colorecLal cancer 1he mechanlsm by whlch Lhese subsLances are relaLed Lo Lhe developmenL of colorecLal cancer ls
unknown

SaLuraLed faLs from dalry producLs do noL have Lhe same carclnogenlc effecL nor do olls conLalnlng olelc acld (eg ollve
coconuL flsh olls) Cmega3 monounsaLuraLed faLLy aclds and omega6 monounsaLuraLed faLLy aclds also appear Lo be
less carclnogenlc Lhan unsaLuraLed or polyunsaLuraLed faLs ln facL recenL epldemlologlc daLa suggesL LhaL hlgh flsh
consumpLlon may provlde a proLecLlve effecL agalnsL developmenL of colorecLal cancer LongLerm dleLs hlgh ln red
meaL or processed meaLs appear Lo lncrease Lhe rlsk of dlsLal colon and recLal cancers
48


1he lngesLlon of a hlghflber dleL may be proLecLlve agalnsL colorecLal cancer llber causes Lhe formaLlon of a sofL bulky
sLool LhaL dlluLes carclnogens lL also decreases colonlc LranslL Llme allowlng less Llme for harmful subsLances Lo
conLacL Lhe mucosa 1he decreased lncldence of colorecLal cancer ln Afrlcans ls aLLrlbuLed Lo Lhelr hlghflber low
anlmalfaL dleL 1hls favorable sLaLlsLlc ls reversed when Afrlcan people adopL a wesLern dleL MeLaanalysls of case
conLrolled sLudles found LhaL reducLlon ln colorecLal cancer rlsk occurs wlLh lncreaslng lnLake of dleLary flber
4


lncreased dleLary lnLake of calclum appears Lo have a proLecLlve effecL on colorecLal mucosa by blndlng wlLh blle aclds
and faLLy aclds 1he resulLlng calclum salLs may have anLlprollferaLlve effecLs decreaslng crypL cell producLlon ln Lhe
mucosa A doublebllnd placeboconLrolled sLudy showed a sLaLlsLlcally slgnlflcanL reducLlon ln Lhe lncldence of
meLachronous colorecLal adenomas
9
CLher dleLary componenLs such as selenlum caroLenolds and vlLamlns A C and
L may have proLecLlve effecLs by scavenglng freeoxygen radlcals ln Lhe colon

A|coho|

Alcohol lnLake of more Lhan 30 g dally has been assoclaLed wlLh lncreased rlsk of developlng colorecLal carclnoma wlLh
rlsk of recLal cancer greaLer Lhan LhaL of colon cancer 8lsk appears greaLer wlLh beer Lhan wlLh wlne
10
Speclflcally
kabaL eL al found LhaL dally beer consumpLlon of 32 ounces or more lncreases Lhe rlsk of recLal cancer ln men (odds
raLlo 33)
11


1obacco

Smoklng parLlcularly when sLarLed aL a young age lncreases Lhe rlsk of colorecLal cancer
12
osslble mechanlsms for
Lumor developmenL lnclude Lhe producLlon of Loxlc polycycllc aromaLlc amlnes and Lhe lnducLlon of anglogenlc
mechanlsms due Lo Lobacco smoke
Cho|ecystectomy
lollowlng cholecysLecLomy blle aclds flow freely lncreaslng exposure Lo Lhe degradlng acLlon of lnLesLlnal bacLerla
1hls consLanL exposure lncreases Lhe proporLlon of carclnogenlc blle acld byproducLs A meLaanalysls by Clovannuccl eL
al revealed an lncreased rlsk of proxlmal colon carclnoma followlng cholecysLecLomy AlLhough a large number of
sLudles suggesL Lhe lncreased rlsk of proxlmal colon cancer ln paLlenLs followlng cholecysLecLomy Lhe daLa are noL
compelllng enough Lo warranL enhanced screenlng ln Lhls paLlenL populaLlon
1

nered|tary actors
1he relaLlve rlsk of developlng colorecLal cancer ls lncreased ln Lhe flrsLdegree relaLlves of affecLed paLlenLs lor
offsprlng Lhe relaLlve rlsk ls 242 (93 Cl 220263) when more Lhan one famlly member ls affecLed Lhe relaLlve rlsk
lncreases Lo 423 (93 Cl 301608) lf Lhe flrsLdegree famlly member ls younger Lhan 43 years aL Lhe Llme of
dlagnosls Lhe rlsk lncrease ls even hlgher
13


8egardlng Lhe personal hlsLory of colorecLal cancer or polyps Cf paLlenLs wlLh colorecLal cancer 30 have synchronous
leslons usually adenomaLous polyps ApproxlmaLely 4030 of paLlenLs have polyps on a followup colonoscopy Cf all
paLlenLs who have adenomaLous polyps dlscovered vla a colonoscopy 29 of Lhem have addlLlonal polyps dlscovered
on a repeaL colonoscopy one year laLer Mallgnancy develops ln 23 of paLlenLs 1he rlsk of cancer ln people who have
had polyps removed ls 2777 Llmes LhaL of Lhe general populaLlon
14

Genet|c D|sorders
am|||a| adenomatous po|ypos|s (A)

lA ls an auLosomal domlnanL lnherlLed syndrome LhaL resulLs ln Lhe developmenL of more Lhan 100 adenomaLous
polyps and a varleLy of exLralnLesLlnal manlfesLaLlons 1he defecL ls ln Lhe Alc gene whlch ls locaLed on chromosome 3
aL locus q21 1he dlsease process causes Lhe formaLlon of hundreds of lnLesLlnal polyps osLeomas of bone desmold
Lumors and occaslonally braln Lumors lndlvldually Lhese polyps are no more llkely Lo undergo mallgnanL
LransformaLlon Lhan are polyps ln Lhe general populaLlon 1he lncreased number of polyps however predlsposes
paLlenLs Lo a greaLer rlsk of cancer lf lefL unLreaLed colorecLal cancer develops ln nearly 100 of Lhese paLlenLs by age
40 Whenever Lhe heredlLary llnk ls documenLed approxlmaLely 20 of lA cases are found Lo be caused by
sponLaneous muLaLlon


nered|tary nonpo|ypos|s co|orecta| cancer

PnCC ls an auLosomal domlnanL lnherlLed syndrome LhaL occurs because of defecLlve mlsmaLch repalr genes locaLed
on chromosomes 2 3 and 7 aLlenLs have Lhe same number of polyps as Lhe general populaLlon buL Lhelr polyps are
more llkely Lo become mallgnanL 1hese paLlenLs also have a hlgher lncldence of endomeLrlal gasLrlc Lhyrold and braln
cancers

1he revlsed AmsLerdam crlLerla are used Lo selecL aLrlsk paLlenLs (all crlLerla musL apply)
O 1hree or more relaLlves who are dlagnosed wlLh an PnCCassoclaLed cancer (colorecLal endomeLrlum small
bowel ureLer or renal pelvls)
O Cne affecLed person ls a flrsLdegree relaLlve of Lhe oLher 2
O Cne or more cases of cancer are dlagnosed before age 30 years
O AL leasL 2 generaLlons are affecLed
O lA has been excluded
O 1umors have undergone a paLhology revlew
nf|ammatory 8owe| D|sease
1he mallgnanL paLhway ln Lhese paLlenLs does noL lnvolve any adenomacarclnoma sequence Cancer rlsk lncreases
wlLh duraLlon of dlsease AfLer 10 years Lhe lncldence of colorecLal cancer ln ulceraLlve collLls (uC) ls approxlmaLely 1
per year aLlenLs should be evaluaLed for dysplasLlc changes vla an annual colonoscopy uysplasla ls a precursor of
cancer and when presenL Lhe rlsk of cancer ls 30

1he lncldence of colorecLal cancer ln paLlenLs wlLh Crohn's dlsease ls 420 Llmes greaLer Lhan LhaL of Lhe general
populaLlon Cancer occurs ln paLlenLs wlLh dlsease of aL leasL 10 years duraLlon 1he average age aL cancer dlagnosls
4633 years ls younger Lhan LhaL of Lhe general populaLlon Cancers ofLen develop ln areas of sLrlcLures and ln de
funcLlonallzed segmenLs of lnLesLlne ln paLlenLs wlLh perlanal Crohn's dlsease mallgnancy ls ofLen presenL ln flsLulous
LracLs aLlenLs wlLh Crohn's collLls should undergo Lhe same survelllance reglmen as Lhose wlLh uC
Workup
Laboratory Stud|es
8ouLlne laboraLory sLudles should lnclude a compleLe blood counL serum chemlsLrles lncludlng llver and renal funcLlon
LesLs and a carclnoembryonlc anLlgen (CLA) LesL A cancer anLlgen (CA) 199 assay lf avallable may also be useful Lo
monlLor Lhe dlsease

Screenlng C8C may demonsLraLe a hypochromlc mlcrocyLlc anemla suggesLlng lron deflclency 1he comblned presence
of vlLamln 812 or folaLe deflclency may resulL ln a normocyLlc or macrocyLlc anemla All men and posLmenopausal
women wlLh lron deflclency anemla requlre a Cl evaluaLlon

Llver funcLlon LesLs are usually parL of Lhe preoperaLlve workup 1he resulLs are ofLen normal even ln paLlenLs wlLh
meLasLases Lo Lhe llver

erform a CLA LesL ln all paLlenLs wlLh recLal cancer A basellne level ls obLalned before surgery and a followup level ls
obLalned afLer surgery lf a prevlously normallzed CLA beglns Lo rlse ln Lhe posLoperaLlve perlod Lhls suggesLs posslble
recurrence A CLA level hlgher Lhan 100 ng/mL usually lndlcaLes meLasLaLlc dlsease and warranLs a Lhorough
lnvesLlgaLlon 1he sLeps of Lhe workup are ouLllned ln llgure 1

ther 1ests
Screen|ng for Co|on and kecta| Cancer

1he process of mallgnanL LransformaLlon from adenoma Lo carclnoma Lakes several years 1he purpose of screenlng ls
Lo eradlcaLe poLenLlal cancers whlle Lhey are sLlll ln Lhe benlgn sLage of Lhe adenomacarclnoma sequence Screenlng
also lncreases Lhe llkellhood of dlscoverlng exlsLlng cancers whlle Lhey are sLlll ln Lhe early sLage
O Averagerlsk screenlng (see below) eople who are asympLomaLlc younger Lhan 30 years and have no oLher
rlsk facLors are consldered aL average rlsk for developlng colorecLal cancer Screenlng of Lhe averagerlsk
populaLlon should begln aL age 30 years and end aL age 73 years
13

O Cualacbased fecal occulL blood LesL (lC81) erform lC81 yearly by LesLlng 2 samples from each of 3
consecuLlve sLools lf any of Lhe 6 sample flndlngs ls poslLlve recommend LhaL Lhe paLlenL have Lhe enLlre colon
sLudled vla colonoscopy or flexlble slgmoldoscopy lC81 has slgnlflcanL falseposlLlve and falsenegaLlve raLes
O SLool unA screenlng (SunA) SunA screenlng ls done uslng polymerase chaln reacLlon of sloughed mucosal cells
ln sLool 1hls LesL evaluaLes for geneLlc alLeraLlons LhaL lead Lo Lhe cancer formaLlon Compared wlLh no LesLlng
SunA LesLlng ls cosL effecLlve and has hlgh senslLlvlLy for lnvaslve cancer
O lecal lmmunochemlcal LesL (ll1) lecal lmmunochemlcal LesLlng uses a monoclonal anLlbody assay Lo ldenLlfy
human hemoglobln 1hls LesL ls more speclflc for lower Cl LracL leslons 1he presence of Lhe globln molecule ls
lndlcaLlve of bleedlng ln Lhe colon and recLum because Lhe globln molecule ls broken down durlng passage
Lhrough Lhe upper Cl LracL
O 8lgld procLoscopy 8lgld procLoslgmoldoscopy can be performed wlLhouL an anesLheLlc allows dlrecL
vlsuallzaLlon of Lhe leslon and provldes an esLlmaLlon of Lhe slze of Lhe leslon and degree of obsLrucLlon 1hls
procedure ls used Lo obLaln blopsles of Lhe leslon assess ulceraLlon and deLermlne Lhe degree of flxaLlon 1he
rlgld procLoscopy ls proven Lo be a hlghly reproduclble meLhod of deLermlnlng Lhe level of recLal cancer and
does noL depend on Lhe operaLor and on Lhe Lechnlque 1herefore lL glves an accuraLe measuremenL of Lhe
dlsLance of Lhe leslon from Lhe anal verge Lhe laLLer ls crlLlcal ln decldlng whlch operaLlon ls approprlaLe 1he
anal verge should be used as preferred landmark because Lhe lowesL edge of Lhe recLal cancer and Lhe anal
verge can be vlsuallzed slmulLaneously durlng rlgld procLoscopy evaluaLlon ln concluslon Lhe level of recLal
cancer musL be conflrmed by rlgld procLoscopy
16

O llexlble slgmoldoscopy (lSlC) erform Lhls LesL every 3 years 8lopsy any leslons ldenLlfled and perform a full
colonoscopy WlLh flexlble slgmoldoscopy leslons beyond Lhe reach of Lhe slgmoldoscope may be mlssed lSlC
lnLroduces slgnlflcanL varlablllLy for Lhe level of recLal cancer and level of recLum lLself 1herefore lSlC should
noL be used Lo deLermlne Lhe level of Lhe recLal cancer
16

O Comblned glucosebased lC81 and flexlble slgmoldoscopy 1heoreLlcally Lhe comblnaLlon of Lhese 2 LesLs may
overcome Lhe llmlLaLlons of each LesL
O uoubleconLrasL barlum enema (uC8L) AlLhough barlum enema ls Lhe LradlLlonal dlagnosLlc LesL for colonlc
polyps and cancer Lhe unlLed SLaLes revenLlve Servlces 1ask lorce (uSS1l) dld noL conslder barlum enema ln
lLs 2008 updaLe of colorecLal cancer screenlng recommendaLlons 1he uSS1l noLed LhaL barlum enema has
subsLanLlally lower senslLlvlLy Lhan modern LesL sLraLegles and has noL been sLudled ln Lrlals of screenlng Lrlals
lLs use as a screenlng LesL for colorecLal cancer ls decllnlng
13

O C1 colonography (C1C) vlrLual colonoscopy (C1C) was lnLroduced ln 1994 AfLer bowel preparaLlon Lhe LhlncuL
axlal colonlc lmages are gaLhered ln boLh prone and suplne poslLlons wlLh hlghspeed hellcal C1 scanner 1hen
Lhe lmages are reconsLlLuLed lnLo a 3dlmenslonal repllca of Lhe enLlre colon and recLum 1hls provldes a good
vlsuallzaLlon of Lhe enLlre colon lncludlng Lhe anLegrade and reLrograde vlews of Lhe flexures and hausLral
folds 8ecause Lhls ls a dlagnosLlc sLudy paLlenLs wlLh poslLlve flndlngs should undergo colonoscoplc evaluaLlon
Lhe same day
O llberopLlc flexlble colonoscopy (llC) llC ls recommended every 310 years Colonoscopy allows full
vlsuallzaLlon of Lhe colon and exclslon and blopsy of any leslons 1he llkellhood ls exLremely low LhaL a new
leslon could develop and progress Lo mallgnancy beLween examlnaLlons
Slgns and sympLoms ln paLlenLs wlLh average rlsk for colon and recLal cancer who should be screened lnclude Lhe
followlng
O no sympLoms and age 3073 years
O no sympLoms requesLlng screenlng
O Change ln bowel hablLs
O 8ecLal and anal bleedlng
O unclear abdomlnal paln
O unclear lrondeflclency anemla
1he uS MulLlSocleLy 1ask lorce on ColorecLal Cancer (uSMS1l) has endorsed varlous cosLeffecLlve screenlng
reglmens Screenlng opLlons for Lhe deLecLlon of adenomaLous polyps and cancer for asympLomaLlc adulLs 30 years and
older lnclude lSlC every 3 years colonoscopy every 10 years uC8L every 3 years or C1C every 3 years 1esLlng opLlons
LhaL prlmarlly deLecL cancer ln asympLomaLlc adulLs 30 years and older lnclude annual glucosebased lC81 wlLh hlgh
LesL senslLlvlLy for cancer annual ll1 wlLh hlghLesL senslLlvlLy for cancer or SunA wlLh hlghLesL senslLlvlLy for cancer
alLhough Lhe opLlmal lnLerval for SunA ls uncerLaln

Lach screenlng LesL has unlque advanLages 1hey have been shown Lo be cosLeffecLlve and have assoclaLed rlsks and
llmlLaLlons ulLlmaLely paLlenL preferences and avallablllLy of LesLlng resources gulde Lhe selecLlon of screenlng LesLs
1he maln dlsadvanLage of Lhe sLrucLural LesLs ls Lhelr requlremenL for bowel preparaLlon 1he prlmary advanLage of
sLrucLural LesLs ls LhaL Lhey can deLecL polyps as well as cancer Consclous sedaLlon ls usually used for colonoscopy lSlC
ls uncomforLable and screenlng beneflL ls llmlLed Lo slgmold colon and recLum 8lsks for colonoscopy uC8L and C1C
may rarely lnclude perforaLlon colonoscopy may also be assoclaLed wlLh bleedlng oslLlve flndlngs on lSlC uC8L and
C1C usually resulL ln referral for colonoscopy 1he advanLages of Lhe sLool LesLs are LhaL Lhey are nonlnvaslve do noL
requlre bowel preparaLlon can be done ln Lhe prlvacy of Lhe paLlenLs home and are more readlly avallable Lo paLlenLs
wlLhouL adequaLe lnsurance coverage or local resources

ln Lhe unlLed SLaLes colon and recLal cancer screenlng raLes have been averaglng beLween 30 and 60 8rounLs and
colleagues sLudled colorecLal cancer screenlng ln Lhe MlllLary PealLhcare SysLem ln Lhls sLudy overall screenlng raLes
were lower ln mlnorlLy groups Lhan ln whlLes Also overall lower screenlng raLes were ldenLlfled ln paLlenLs younger
Lhan 63 years AlLhough eLhnlclLyrelaLed genderrelaLed and agerelaLed dlsparlLles were observed screenlng raLes
were lmproved ln Lhls equalaccess healLh care sysLem when compared wlLh naLlonal averages
17

Screen|ng of h|ghr|sk pat|ents
eople aL lncreased rlsk for colorecLal cancer lnclude Lhose wlLh affecLed flrsLdegree relaLlves Lhose wlLh a famlly
hlsLory of lA or PnCC and Lhose wlLh a personal hlsLory of adenomaLous polyps colorecLal cancer or l8u
O llrsLdegree relaLlve affecLed Cffer famlly members Lhe same screenlng LesLs as Lhe general populaLlon
however begln Lhe screenlng aL age 40 years raLher Lhan age 30 years 1hese people ofLen undergo
colonoscopy as Lhelr lnlLlal screenlng LesL parLlcularly lf Lhe relaLlve was dlagnosed wlLh cancer aL a young age
O lamlly hlsLory of lA CeneLlc counsellng and geneLlc LesLlng are recommended Lo deLermlne wheLher Lhe
person ls a gene carrler CurrenL LesLs are approxlmaLely 80 accuraLe ln Lhe remalnlng 20 Lhe muLaLlon
cannoL be ldenLlfled CeneLlc LesLlng ls useful only lf Lhe LesL resulL ls poslLlve or lf Lhe LesL ls a Lrue negaLlve (le
muLaLlon presenL ln oLher famlly members are noL ldenLlfled ln Lhe paLlenL belng LesLed) llexlble
slgmoldoscopy should be offered Lo known gene carrlers and persons wlLh an lndeLermlnaLe carrler sLaLus
every year Lo look for polyps When polyposls develops conslder colecLomy
O lamlly hlsLory of PnCC CeneLlc counsellng and geneLlc LesLlng should be offered Lo lndlvlduals whose famlly
hlsLorles meeL Lhe AmsLerdam crlLerla (see Causes above) aLlenLs wlLh documenLed PnCC should undergo
colonoscopy every 12 years when 2040 years of age and every year when older Lhan 40 years Slnce Lhese
cancers Lend Lo be locaLed on Lhe rlghL slde of Lhe colon flexlble slgmoldoscopy ls noL recommended
O ersonal hlsLory of adenomaLous polyps aLlenLs who have adenomaLous polyps removed durlng colonoscopy
should have a repeaL examlnaLlon aL 1 Lo 3 years lf Lhe flndlngs of Lhls examlnaLlon are normal follow up aL 3
years
O ersonal hlsLory of colorecLal cancer aLlenLs who have colorecLal cancer and undergo resecLlon for cure
should have a repeaL colonoscopy afLer 1 year lf Lhls examlnaLlon reveals no abnormallLles follow up aL 3
years ln Lhe absence of dlsease perform colonoscopy every 3 years LhereafLer
O ersonal hlsLory of l8u Survelllance colonoscopy ls performed Lo look for dysplasla as a marker for colorecLal
cancer ln paLlenLs wlLh longsLandlng l8u 1hese paLlenLs should undergo colonoscopy every 12 years afLer 8
years of dlffuse dlsease or afLer 13 years of locallzed dlsease 8andom blopsles are performed aL speclflc
lnLervals LhroughouL Lhe colon and recLum ColecLomy ls recommended when dysplasla ls presenL
Slgns and sympLoms ln paLlenLs aL hlghrlsk for colon and recLal cancer due Lo famlly hlsLory who should be lncluded ln
survelllance programs lnclude Lhe followlng
O lamlly hlsLory of colon and recLal cancer
O llrsLdegree relaLlve wlLh adenoma aged younger Lhan 60 years
O CeneLlc famlly syndromes
O PnCC
O lA
Slgns and sympLoms ln paLlenLs aL hlghrlsk for colon and recLal cancer due Lo personal hlsLory who should be lncluded
ln survelllance programs lncludes Lhe followlng
O ersonal hlsLory of lnflammaLory bowel dlsease
O ersonal hlsLory of adenomas
O ersonal hlsLory of colon and recLal cancer
O ersonal hlsLory of geneLlc famlly syndromes
n|sto|og|c |nd|ngs
PlsLopaLhologlc feaLures such as poor dlfferenLlaLlon lymphovascular and/or perlneural lnvaslon 14 Lumor sLage and
cllnlcal flndlngs such as obsLrucLlon or perforaLlon and elevaLed preoperaLlve CLA levels are all assoclaLed wlLh
lncreased recurrence raLes and worse survlval
18

Stag|ng
Dukes C|ass|f|cat|on
ln 1932 CuLhberL L uukes a paLhologlsL aL SL Mark PosplLal ln Lngland lnLroduced a sLaglng sysLem for recLal cancer
Pls sysLem dlvlded Lumor classlflcaLlon lnLo 3 sLages as follows
O 1hose llmlLed Lo Lhe recLal wall (uukes A)
O 1hose LhaL exLended Lhrough Lhe recLal wall lnLo exLrarecLal Llssue (uukes 8)
O 1hose wlLh meLasLases Lo reglonal lymph nodes (uukes C)
1hls sysLem was modlfled by oLhers Lo lnclude subdlvlslons of sLages 8 and C as follows
SLage 8 was dlvlded lnLo 81 (le Lumor peneLraLlon lnLo muscularls proprla) and 82 (le Lumor peneLraLlon Lhrough
muscularls proprla)
SLage C was dlvlded lnLo C1 (le Lumor llmlLed Lo Lhe recLal wall wlLh nodal lnvolvemenL) and C2 (le Lumor peneLraLlng
Lhrough Lhe recLal wall wlLh nodal lnvolvemenL)
SLage u was added Lo lndlcaLe dlsLanL meLasLases
1umor Node Metastas|s (1NM) System
1hls sysLem was lnLroduced ln 1934 by Lhe Amerlcan !olnL CommlLLee on Cancer (A!CC) and Lhe lnLernaLlonal unlon
AgalnsL Cancer (luAC) 1he 1nM sysLem ls a unlversal sLaglng sysLem for all solld cancers LhaL ls based on cllnlcal and
paLhologlc lnformaLlon Lach caLegory ls lndependenL
nelLher Lhe uukes nor Lhe 1nM sysLem lncludes prognosLlc lnformaLlon such as hlsLologlc grade vascular or perlneural
lnvaslon or Lumor unA ploldy 1nM sLaglng of recLal cancer correlaLes well wlLh 3year survlval raLes of paLlenLs wlLh
recLal cancer (see Lhe 1nM sLagedependenL 3year survlval raLe for recLal carclnomas)
1NM c|ass|f|cat|on for cancer of the co|on and rectum (AICC)
rlmary Lumor (1) lncludes Lhe followlng
O 1x rlmary Lumor cannoL be assessed or depLh of peneLraLlon noL speclfled
O 10 no evldence of prlmary Lumor
O 1ls Carclnoma ln slLu (mucosal) lnLraeplLhellal or lnvaslon of Lhe lamlna proprla
O 11 1umor lnvades submucosa
O 12 1umor lnvades muscularls proprla
O 13 1umor lnvades Lhrough Lhe muscularls proprla lnLo Lhe subserosa or lnLo nonperlLoneallzed perlcollc or
perlrecLal Llssue
O 14 1umor dlrecLly lnvades oLher organs or sLrucLures and/or perforaLes Lhe vlsceral perlLoneum
8eglonal lymph nodes (n) lnclude Lhe followlng
O nx 8eglonal lymph nodes cannoL be assessed
O n0 no reglonal lymph node meLasLasls
O n1 MeLasLasls ln 13 perlcollc or perlrecLal lymph nodes
O n2 MeLasLasls ln 4 or more perlcollc or perlrecLal lymph nodes
O n3 MeLasLasls ln any lymph node along Lhe course of a named vascular Lrunk
ulsLanL meLasLasls (M) lnclude Lhe followlng
O Mx resence of meLasLasls cannoL be assessed
O M0 no dlsLanL meLasLasls
O M1 ulsLanL meLasLasls
1able 1 Comparlson of A!CC ueflnlLlon of 1nM SLaglng SysLem Lo uukes ClasslflcaLlon
8ecLal Cancer SLages 1nM SLaglng uuke
SLaglng
3?ear
Survlval
SLage l 1
12
n
0
M
0
A 90
SLage ll A 1
3
n
0
M
0
8 6083
8 1
4
n
0
M
0
6083
SLage l A 1
12
n
1
M
0
C 3360
8 1
34
n
1
M
0
3342
C 1
14
n
2
M
0
2327
SLage lv 1
14
n
02
M
1
37

1he 1nM sLage dependenL 3year survlval raLe for recLal carclnomas ls as follows
18

O SLage l 90
O SLage ll 6083
O SLage lll 2760
O SLage lv 37
1reatment
Med|ca| Care
1he surglcal deflnlLlon of Lhe recLum dlffers from Lhe anaLomlcal deflnlLlon surgeons deflne Lhe recLum as sLarLlng aL
Lhe level of Lhe sacral promonLory whlle anaLomlsLs deflne Lhe recLum as sLarLlng aL Lhe level of Lhe 3
rd
sacral verLebra
1herefore Lhe measured lengLh of Lhe recLum varles from 12 cm Lo 13 cm 1he recLum ls dlfferenL Lhan Lhe resL of Lhe
colon ln LhaL Lhe ouLer layer ls made of longlLudlnal muscle 1he recLum conLalns 3 folds namely valves of PousLon
1he superlor (10 cm Lo 12 cm) and lnferlor (4 cm Lo 7 cm) folds are locaLed on Lhe lefL slde and mlddle fold (8 cm Lo 10
cm) ls locaLed aL Lhe rlghL slde

naLlonal Comprehenslve Cancer neLwork guldellnes deflne recLal cancer as cancer locaLed wlLhln 12 cm of Lhe anal
verge by rlgld procLoscopy 1hls deflnlLlon was developed by Lhe uuLch ColorecLal Cancer Croup sLudy whlch found
LhaL Lhe rlsk of recurrence of recLal cancer depends on Lhe locaLlon of Lhe cancer unlvarlaLe subgroup analyses
showed LhaL Lhe LreaLmenL effecL for surgery alone vs preoperaLlve radloLherapy plus surgery was noL slgnlflcanL ln
paLlenLs whose cancer (1nM sLage l Lo lv) was locaLed beLween 101 cm and 13 cm from Lhe anal verge
19


ueLermlnaLlon of opLlmal LreaLmenL plan for paLlenLs wlLh recLal cancer lnvolves a complex declslonmaklng process
SLrong conslderaLlons should be glven Lo Lhe lnLenL of surgery posslble funcLlonal ouLcome and preservaLlon of anal
conLlnence and genlLourlnary funcLlons 1he flrsL sLep lnvolves achlevemenL of cure because Lhe rlsk of pelvlc
recurrence ls hlgh ln paLlenLs wlLh recLal cancer and locally recurrenL recLal cancer has a poor prognosls luncLlonal
ouLcome of dlfferenL LreaLmenL modallLles lnvolves resLoraLlon of bowel funcLlon wlLh accepLable anal conLlnence and
preservaLlon of genlLourlnary funcLlons reservaLlon of boLh anal and recLal reservolr funcLlon ln LreaLmenL of recLal
cancer ls hlghly preferred by paLlenLs SphlncLersavlng procedures for recLal cancer are now consldered Lhe sLandard of
care
20


lacLors lnfluenclng sphlncLer and organ preservaLlon ln paLlenLs wlLh recLal cancer can be descrlbed as follows
20

actors |nf|uenc|ng sph|ncter preservat|on
O Surgeon Lralnlng
O Surgeon volume
O neoad[uvanL chemoradloLherapy
actors assoc|ated w|th d|ff|cu|t sph|ncter preservat|on
O Male sex
O Morbld obeslLy
O reoperaLlve lnconLlnence
O ulrecL lnvolvemenL of anal sphlncLer muscles wlLh carclnoma
O 8ulky Lumors wlLhln 3 cm from Lhe anal verge
at|ent se|ect|on for |oca| exc|s|on
O Leslons locaLed ln low recLum (wlLhln 810 cm)
O Leslons occupylng less Lhan one Lhlrd of Lhe recLal clrcumference
O Moblle exophlLlc or polypold leslons
O Leslons less Lhan 3 cm ln slze
O 11 leslons
O Low grade Lumor (well or moderaLely dlfferenLlaLed)
O negaLlve nodal sLaLus (cllnlcal and radlographlc)
D|sadvantages of Ak
O need for permanenL colosLomy
O SlgnlflcanLly hlgher shorLLerm morbldlLy and morLallLy
O SlgnlflcanLly hlgher longLerm morbldlLles
O Plgher raLe of sexual and urlnary dysfuncLlon

Surg|ca| Care
aLlenLrelaLed LumorrelaLed LreaLmenL and surgeonrelaLed facLors lnfluence Lhe ablllLy Lo resLore lnLesLlnal
conLlnulLy ln paLlenLs wlLh recLal cancer
1ransana| Lxc|s|on
1he local Lransanal exclslon of recLal cancer ls reserved for earlysLage cancers ln a selecL group of paLlenLs 1he leslons
amenable for local exclslon are small ( 3 cm ln slze) occupylng less Lhan a Lhlrd of a clrcumference of Lhe recLum
preferably exophyLlc/polypold superflclal and moblle (1
1
and 1
2
leslons) lowgrade Lumors (well or moderaLely
dlfferenLlaLed) LhaL are locaLed ln low ln Lhe recLum (wlLhln 8 cm of Lhe anal verge) 1here should also be no palpable or
radlologlc evldence of enlarged mesenLerlc lymph nodes 1he llkellhood of lymph node lnvolvemenL ln Lhls Lype of
leslon ranges from 012
2021


reoperaLlve L8uS should be performed lf nodes are ldenLlfled as suggesLlve of cancer do noL perform Lransanal
exclslon 1he leslon ls exclsed wlLh Lhe full Lhlckness of Lhe recLal wall leavlng a 1cm margln of normal Llssue 1he
defecL ls usually closed however some surgeons leave lL open unfavorable paLhologlc feaLures such as poslLlve
resecLlon marglns lymphovascular lnvaslon lymph node meLasLasls perlneural lnvaslons and recurrenL leslon aL
followup evaluaLlons mandaLe salvage resecLlon usually an abdomlnal perlneal resecLlon or procLoslgmoldecLomy
wlLh coloanal anasLomosls ls performed as a salvage resecLlon followlng fallure of local exclslon
21


1he advanLages of local exclslon lnclude rapld recovery mlnlmal effecL on sphlncLer funcLlon and relaLlvely low
perloperaLlve morbldlLy and morLallLy 8ecovery ls usually rapld 1he 3year survlval raLe afLer Lransanal exclslon ranges
from 63100 (Lhese flgures lnclude some paLlenLs wlLh 1
2
leslons) 1he local recurrence raLe ranges from 040
aLlenLs wlLh leslons LhaL dlsplay unfavorable hlsLologlc feaLures buL are exclsed compleLely may be LreaLed wlLh
ad[uvanL radlaLlon Lherapy

Cancer recurrence followlng Lransanal exclslon of early recLal cancer has been sLudled by Welser eL al
22
lallures due Lo
Lransanal exclslon are mosLly advanced local dlsease and are noL unlformly salvageable wlLh radlcal pelvlc exclslon
1hese paLlenLs may requlre exLended pelvlc dlssecLlon wlLh en bloc resecLlon of ad[acenL pelvlc organs such as Lhe
pelvlc slde wall wlLh auLonomlc nerves coccyx prosLaLe semlnal veslcle bladder vaglna ureLer ovary and uLerus 1he
longLerm ouLcome ln paLlenLs wlLh recurrenL recLal carclnoma who undergo radlcal resecLlon ls less favorable Lhan
expecLed relaLlve Lo Lhe early sLage of Lhelr lnlLlal recLal carclnoma
22


ln summary Lhe LreaLmenL of 1
1
and 1
2
recLal cancers conLlnues Lo be challenglng Local exclslon ls assoclaLed wlLh
hlgher raLe of recurrence especlally ln 1
2
leslons ulLlmaLely 1320 of paLlenLs may experlence recurrence When
local recurrence ls deLecLed paLlenLs usually have advanced dlsease requlrlng exLenslve pelvlc exclslons 1herefore
sLrlcL selecLlon crlLerla are essenLlal when conslderlng local exclslon All paLlenLs should be lnformed of Lhe rlsk of local
recurrence and lower cure raLes assoclaLed wlLh recurrence
222023

Lndocav|tary kad|at|on
1hls radloLherapy meLhod dlffers from exLernalbeam radlaLlon Lherapy ln LhaL a larger dose of radlaLlon can be
dellvered Lo a smaller area over a shorLer perlod SelecLlon crlLerla for Lhls procedure are slmllar Lo Lhose for Lransanal
exclslon 1he leslon can be as far as 10 cm from Lhe anal verge and no larger Lhan 3 cm LndocavlLary radlaLlon ls
dellvered vla a speclal procLoscope and ls performed ln an operaLlng room wlLh sedaLlon 1he paLlenL can be dlscharged
on Lhe same day

A LoLal of 6 appllcaLlon of hlghdose (20Cy Lo 30 Cy) lowvolLage radlaLlon (30kv) ls glven over Lhe course of 6 weeks
Lach radloLherapy sesslon produces a rapld shrlnkage of Lhe recLal cancer leslon An addlLlonal boosLer dose can be
glven Lo Lhe Lumor bed 1he overall survlval raLe ls 83 alLhough Lhe local recurrence raLe as hlgh as 30
21

1ransana| Lndoscop|c M|crosurgery (1LM)
1ransanal endoscoplc mlcrosurgery ls anoLher form of local exclslon LhaL uses a speclal operaLlng procLoscope LhaL
dlsLends Lhe recLum wlLh lnsufflaLed carbon dloxlde and allows Lhe passage of dlssecLlng lnsLrumenLs 1hls meLhod can
be used on leslons locaLed hlgher ln Lhe recLum and even ln Lhe dlsLal slgmold colon 1ransanal endoscoplc
mlcrosurgery has noL come lnLo wlde use yeL because of a slgnlflcanL learnlng curve and a lack of avallablllLy
Sph|ncterSpar|ng rocedures
rocedures are descrlbed LhaL use Lhe LradlLlonal open Lechnlque All of Lhese procedures excepL Lhe perlneal porLlons
can also be performed uslng laparoscoplc Lechnlques wlLh excellenL resulLs 1he nuances of Lhe laparoscoplc Lechnlque
used are beyond Lhe scope of Lhls dlscusslon

Low anter|or resect|on (LAk)

LA8 ls generally performed for leslons ln Lhe mlddle and upper Lhlrd of Lhe recLum and occaslonally for leslons ln Lhe
lower Lhlrd 8ecause Lhls ls a ma[or operaLlon paLlenLs who undergo LA8 should be ln good healLh 1hey should noL
have any preexlsLlng sphlncLer problems or evldence of exLenslve local dlsease ln Lhe pelvls

aLlenLs wlll noL have a permanenL colosLomy buL should be lnformed LhaL a Lemporary colosLomy or lleosLomy may be
necessary 1hey also musL be wllllng Lo accepL Lhe posslblllLy of sllghLly lessLhanperfecL conLlnence afLer surgery
alLhough Lhls ls noL usually a ma[or problem
CLher posslble dlsLurbances ln funcLlon lnclude LranslenL urlnary dysfuncLlon secondary Lo weakenlng of Lhe deLrusor
muscle 1hls occurs ln 313 of paLlenLs Sexual dysfuncLlon ls more promlnenL and lncludes reLrograde e[aculaLlon and
lmpoLence ln Lhe pasL Lhls has occurred ln 370 of men buL recenL reporLs lndlcaLe LhaL Lhe currenL lncldence ls
lower
24


1he operaLlon enLalls full moblllzaLlon of Lhe recLum slgmold colon and usually Lhe splenlc flexure MoblllzaLlon of
Lhe recLum requlres a Lechnlque called LoLal mesorecLal exclslon (1ML) 1ML lnvolves sharp dlssecLlon ln Lhe avascular
plane LhaL ls creaLed by Lhe envelope LhaL separaLes Lhe enLlre mesorecLum from Lhe surroundlng sLrucLures 1hls
lncludes Lhe anLerlor perlLoneal reflecLlon and uenonvllllers fascla anLerlorly and preserves Lhe lnferlor hypogasLrlc
plexus posLerlorly and laLerally 1ML ls performed under dlrecL vlsuallzaLlon MesorecLal spread can occur by dlrecL
Lumor spread Lumor exLenslon lnLo lymph nodes or perlneural lnvaslon of Lumor
162423


1ML ylelds a lower local recurrence raLe (4) Lhan Lransanal exclslon (20) buL lL ls assoclaLed wlLh a hlgher raLe of
anasLomoLlc leak (11) lor Lhls reason 1ML may noL be necessary for leslons ln Lhe upper Lhlrd of Lhe recLum 1he
dlsLal resecLlon margln varles dependlng on Lhe slLe of Lhe leslon A 2cm margln dlsLal Lo Lhe leslon musL be achleved
lor Lhe Lumors of Lhe dlsLal recLum less Lhan 3 cm from Lhe anal verge Lhe mlnlmally accepLed dlsLal margln ls 1 cm ln
Lhe fresh speclmen ulsLal lnLramural spread beyond 1 cm occurs rarely ulsLal spread beyond 1 cm ls assoclaLed wlLh
aggresslve Lumor behavlor or advanced Lumor sLage
16


1he procedure ls performed wlLh Lhe paLlenL ln Lhe modlfled llLhoLomy poslLlon wlLh Lhe buLLocks sllghLly over Lhe edge
of Lhe operaLlng Lable Lo allow easy access Lo Lhe recLum
23
(See Lhe Lable below) A clrcular sLapllng devlce ls used Lo
creaLe Lhe anasLomosls A doublesLapled Lechnlque ls performed 1hls enLalls LransecLlon of Lhe recLum dlsLal Lo Lhe
Lumor from wlLhln Lhe abdomen uslng a llnear sLapllng devlce 1he proxlmal resecLlon margln ls dlvlded wlLh a purse
sLrlng devlce

AfLer slzlng Lhe lumen Lhe deLached anvll of Lhe clrcular sLapler ls lnserLed lnLo Lhe proxlmal margln and secured wlLh
Lhe pursesLrlng suLure 1he clrcular sLapler ls lnserLed carefully lnLo Lhe recLum and Lhe cenLral shafL ls pro[ecLed
Lhrough or near Lhe llnear sLaple llne 1hen Lhe anvll ls engaged wlLh Lhe cenLral shafL and afLer compleLely closlng Lhe
clrcular sLapler Lhe devlce ls flred 1wo rlngs of sLaples creaLe Lhe anasLomosls and a clrcular rlm or donuL of Llssue
from Lhe proxlmal and dlsLal marglns ls removed wlLh Lhe sLapllng devlce

1able 2 AccepLable Mlnlmal ulsLal and roxlmal 8esecLlonal Marglns for 8ecLal Cancer
16

kesect|on Marg|ns rox|ma| kesect|on Marg|n
(cm)
D|sta| kesect|on Marg|n (cm)
dea| Marg|ns 3 cm or more 2 cm or more
M|n|ma||y acceptab|e marg|ns 3 cm or more 1 cm or more

1he anasLomoLlc leak raLe wlLh Lhls Lechnlque ranges from 311 for mlddleLhlrd and upperLhlrd anasLomosls and Lo
20 for lowerLhlrd anasLomosls lor Lhls reason some surgeons choose Lo proLecL Lhe lowerLhlrd anasLomosls by
creaLlng a Lemporary dlverLlng sLoma 1hls ls especlally lmporLanL when paLlenLs have recelved preoperaLlve radlaLlon
Lherapy 1he raLe of sLenosls ls approxlmaLely 320 A handsewn anasLomosls may be performed lf preferred Lhe
anasLomosls ls performed as a slnglelayer Lechnlque 1he leak and sLenosls raLes are Lhe same

ln 80 resecLlon Lhe lnferlor mesenLerlc arLery (lMA) should be exclsed aL lLs orlgln buL Lhls rule ls noL mandaLed by
avallable supporLlve evldence aLlenLs wlLh nonenbloc resecLlon poslLlve radlal marglns poslLlve proxlmal and dlsLal
margln resldual lymph node dlsease and lncompleLe preoperaLlve and lnLraoperaLlve sLaglng would noL be consldered
Lo have compleLe resecLlon of cancer (80 resecLlon)
16
aLlenLs wlLh 81 and 82 resecLlon are consldered Lo have an
lncompleLe resecLlon for cure lncompleLe 81 and 82 resecLlon does noL change Lhe 1nM sLage buL affecLs Lhe
curablllLy
16

Co|oana| anastomos|s (CAA)

very dlsLal recLal cancers LhaL are locaLed [usL above Lhe sphlncLer occaslonally can be resecLed wlLhouL Lhe need for a
permanenL colosLomy 1he procedure ls as already descrlbed however Lhe pelvlc dlssecLlon ls carrled down Lo below
Lhe level of Lhe levaLor anl muscles from wlLhln Lhe abdomen A sLralghLLube coloanal anasLomosls (CAA) can be
performed uslng Lhe doublesLapled Lechnlque or a handsewn anasLomosls can be performed Lransanally
24


1he funcLlonal resulLs of Lhls procedure have been poor ln some paLlenLs who experlence lncreased frequency and
urgency of bowel movemenLs as well as some lnconLlnence Lo flaLus and sLool An alLernaLlve Lo Lhe sLralghLLube CAA
ls creaLlon of a colonlc ! pouch 1he pouch ls creaLed by foldlng a loop of colon on lLself ln Lhe shape of a ! A llnear
sLapllng or cuLLlng devlce ls lnserLed lnLo Lhe apex of Lhe ! and Lhe sLapler creaLes an ouLer sLaple llne whlle dlvldlng Lhe
lnner sepLum 1he !pouch anal anasLomosls can be sLapled or hand sewn

An alLernaLlve Lo dolng Lhe enLlre dlssecLlon from wlLhln Lhe abdomen ls Lo begln Lhe operaLlon wlLh Lhe paLlenL ln Lhe
prone [ackknlfe poslLlon 1he perlneal porLlon of Lhls procedure lnvolves an lnLersphlncLerlc dlssecLlon vla Lhe anus up
Lo Lhe level of Lhe levaLor anl muscles AfLer Lhe perlneal porLlon ls compleLe Lhe paLlenL ls Lurned Lo Lhe modlfled
llLhoLomy poslLlon and Lhe abdomlnal porLlon ls performed LlLher a sLralghLLube or colonlc !pouch anal anasLomosls
can be creaLed however boLh musL be hand sewn
24


1he advanLages of Lhe ! pouch lnclude decreased frequency and urgency of bowel movemenLs because of Lhe lncreased
capaclLy of Lhe pouch A Lemporary dlverLlng sLoma ls performed rouLlnely wlLh any coloanal anasLomosls
Abdom|na| per|nea| resect|on (Ak)

A8 ls performed ln paLlenLs wlLh lowerLhlrd recLal cancers A8 should be performed ln paLlenLs ln whom negaLlve
margln resecLlon wlll resulL ln loss of anal sphlncLer funcLlon 1hls lncludes paLlenLs wlLh lnvolvemenL of Lhe sphlncLers
preexlsLlng slgnlflcanL sphlncLer dysfuncLlon or pelvlc flxaLlon and someLlmes ls a maLLer of paLlenL preference

A 2Leam approach ls ofLen used wlLh Lhe paLlenL ln modlfled llLhoLomy poslLlon 1he abdomlnal Leam moblllzes Lhe
colon and recLum LransecLs Lhe colon proxlmally and creaLes an endslgmold colosLomy 1he perlneal Leam beglns by
closlng Lhe anus wlLh a pursesLrlng suLure and maklng a generous elllpLlcal lnclslon 1he lnclslon ls carrled Lhrough Lhe
faL uslng elecLrocauLery 1he lnferlor recLal vessels are llgaLed and Lhe anococcygeal llgamenL ls dlvlded 1he dlssecLlon
plane conLlnues posLerlorly anLerlor Lo Lhe coccyx Lo Lhe level of Lhe levaLor anl muscles

1hen Lhe surgeon breaks Lhrough Lhe muscles and reLrleves Lhe speclmen LhaL has been placed ln Lhe pelvls 1he
speclmen ls broughL ouL Lhrough Lhe posLerlor openlng and Lhe anLerlor dlssecLlon ls conLlnued carefully Care musL be
Laken Lo avold Lhe prosLaLlc capsule ln Lhe male and Lhe vaglna ln Lhe female (unless posLerlor vaglnecLomy was
planned) 1he speclmen ls removed Lhrough Lhe perlneum and Lhe wound ls lrrlgaLed coplously A closedsucLlon draln
ls lefL ln place and Lhe perlneal wound ls closed ln layers uslng absorbable suLures uurlng Lhls Llme Lhe abdomlnal
Leam closes Lhe pelvlc perlLoneum (Lhls ls noL mandaLory) closes Lhe abdomen and maLures Lhe colosLomy
24


ln paLlenLs who have recLal cancer wlLh ad[acenL organ lnvaslon en bloc resecLlon should be performed ln order Lo noL
compromlse cure 1hls slLuaLlon ls encounLered ln 13 of recLal cancer paLlenLs 8ecLal carclnoma mosL commonly
lnvades Lhe uLerus adnexa posLerlor vaglnal wall and bladder 1he urlnary bladder ls Lhe organ mosL commonly
lnvolved ln locally advanced recLal carclnoma LxLended en bloc resecLlon may lnvolve parLlal or compleLe
cysLecLomy
1624


lnadequaLe sampllng of lymph nodes may reflecL nononcologlc resecLlon or lnadequaLe lnspecLlon of paLhologlc
speclmens 1he use of more exLended pelvlc lymphadenecLomy has been sLudled for recLal cancer LxLended
lymphadenecLomy lnvolves removal of all lymph nodes along Lhe lnLernal lllac and common lllac arLerles 1hls
procedure has been assoclaLed wlLh slgnlflcanLly hlgher sexual and urlnary dysfuncLlon wlLhouL any addlLlonal beneflL ln
local recurrence especlally ln paLlenLs wlLh ad[uvanL radloLherapy
18


1reatment of co|orecta| cancer w|th ||ver metastas|s

ChemoLherapeuLlc reglmens for llver meLasLasls lncludlng sysLemlc and lnLrahepaLlc admlnlsLraLlon have only had
llmlLed beneflL SysLemlc chemoLherapy had 1828 response raLes lL ls well accepLed LhaL llver resecLlons ln selecLed
paLlenLs are beneflclal Cverall 3year survlval raLes followlng surglcal resecLlon of llver meLasLasls vary from 20 40
Ad[uvant Med|ca| Care
A mulLldlsclpllnary approach LhaL lncludes colorecLal surgery medlcal oncology and radlaLlon oncology ls requlred for
opLlmal LreaLmenL of paLlenLs wlLh recLal cancer 1he Llmlng of surglcal resecLlon ls dependenL on Lhe slze locaLlon
exLenL and grade of Lhe recLal carclnoma 1he number of lymph nodes removed (12 or more mlnlmum 10) aL Lhe Llme
of surgery lmpacLs sLaglng accuracy and prognosls

AlLhough radlcal resecLlon of recLum ls Lhe malnsLay of Lherapy surgery alone has a hlgh recurrence raLes 1he local
recurrence raLe for recLal cancers LreaLed wlLh surgery alone ls 3030 8ecLal adenocarclnomas are senslLlve Lo
lonlzlng radlaLlon 8adlaLlon Lherapy can be dellvered preoperaLlvely lnLraoperaLlvely or posLoperaLlvely and wlLh or
wlLhouL chemoLherapy

1umor sLage grade number of lymph node meLasLasls lymphovascular lnvolvemenL slgneL cell appearance
achlevemenL of negaLlve radlal marglns and dlsLance from Lhe radlal margln are lmporLanL prognosLlc lndlcaLors of
local and dlsLanL recurrences Low anLerlor (LA8) or abdomlnalperlneal resecLlon (A8) ln con[uncLlons wlLh LoLal
mesorecLal exclslon (1ML) should be performed for opLlmal surglcal Lherapy

Ad[uvant rad|at|on therapy

reoperaLlve radlaLlon Lherapy has many poLenLlal advanLages lncludlng Lumor downsLaglng an lncrease ln
resecLablllLy posslbly permlLLlng Lhe use of a sphlncLersparlng procedure and a decrease ln Lumor vlablllLy whlch may
decrease Lhe rlsk of local recurrence reoperaLlve radlaLlon Lherapy works beLLer ln welloxygenaLed Llssues prlor Lo
surgery osLoperaLlvely Llssues are relaLlvely hypoxlc as a resulL of surgery and may be more reslsLanL Lo radloLherapy
lf paLlenLs have posLoperaLlve compllcaLlons Lhere may be delay ln lnlLlaLlng ad[uvanL Lherapy reoperaLlve radlaLlon
Lherapy also mlnlmlzes Lhe radlaLlon exposure of small bowel loops due Lo pelvlc dlsplacemenL and adheslons followlng
surgery
2423


1he dlsadvanLages of preoperaLlve radlaLlon Lherapy lnclude delay ln deflnlLlve resecLlon posslble loss of accuraLe
paLhologlc sLaglng posslble overLreaLmenL of earlysLage (sLage l and ll) recLal cancer and lncreased posLoperaLlve
compllcaLlons and morbldlLy and morLallLy raLes secondary Lo radlaLlon ln[ury reoperaLlve radlaLlon Lherapy
decreases Lhe rlsk of Lumor recurrence ln paLlenLs wlLh sLage ll or lll dlsease however Lhls does noL LranslaLe lnLo a
decrease ln dlsLanL meLasLases or an lncrease ln survlval raLe Some recenL reporLs clLe an lncrease ln survlval however
Lhls ls sLlll Lhe mlnorlLy oplnlon

ln sum preoperaLlve radloLherapy may be effecLlve ln lmprovlng local conLrol ln locallzed recLal cancer buL ls only of
marglnal beneflL ln aLLalnmenL of lmproved overall survlval lL does noL dlmlnlsh Lhe need for permanenL colosLomles
and lL may lncrease Lhe lncldence of posLoperaLlve surglcal lnfecLlons lL also does noL decrease Lhe lncldence of long
Lerm effecLs on recLal and sexual funcLlon
26
1he auLhors recommend preoperaLlve chemoradlaLlon Lherapy ln paLlenLs
wlLh large bulky cancers and wlLh obvlous nodal lnvolvemenL
24


1he advanLages of posLoperaLlve radlaLlon Lherapy lnclude lmmedlaLe deflnlLlve resecLlon and accuraLe paLhologlc
sLaglng lnformaLlon before beglnnlng lonlzlng radlaLlon 1he dlsadvanLages of posLoperaLlve radlaLlon Lherapy lnclude
posslble delay ln ad[uvanL radlaLlon Lherapy lf posLoperaLlve compllcaLlons ensue no effecL on Lumor cell spread aL Lhe
Llme of surgery and decreased effecL of radlaLlon ln Llssues wlLh surglcallylnduced hypoxla ubllshed randomlzed
Lrlals suggesL LhaL preoperaLlve or posLoperaLlve radlaLlon Lherapy appears Lo have a slgnlflcanL lmpacL on local
recurrence buL does noL lncrease survlval raLes
24


ntraoperat|ve rad|at|on therapy

lnLraoperaLlve radlaLlon Lherapy ls recommended ln paLlenLs wlLh large bulky flxed unresecLable cancers 1he dlrecL
dellvery of hlghdose radloLherapy ls belleved Lo lmprove local dlsease conLrol lnLraoperaLlve radlaLlon Lherapy
requlres speclallzed expenslve operaLlng room equlpmenL llmlLlng lLs use

Ad[uvant chemotherapy

ChemoLherapy opLlons for colon and recLal cancer have greaLly expanded ln recenL years buL Lhe efflcacy of
chemoLherapy remalns lncompleLe and lLs LoxlclLles remaln subsLanLlal ComblnaLlon Lherapy wlLh use of as many drugs
as posslble ls needed for maxlmal effecL agalnsL recLal cancer

1he mosL useful chemoLherapeuLlc agenL for colorecLal carclnoma ls 3fluorouracll (3lu) an anLlmeLabollLe 1he
prodrug 2deoxy3floxurldlne (3luu8) ls rapldly converLed Lo 3lu and ls used for meLasLaLlc llver dlsease by
conLlnuous lnLrahepaLlc lnfuslon lluorouracll ls a fluorlnaLed pyrlmldlne whlch blocks Lhe formaLlon of Lhymldyllc acld
and unA synLhesls Cllnlcally lL offers good radlosenslLlzaLlon wlLhouL severe slde effecLs alLhough dlarrhea can be
dose llmlLlng and lf severe llfeLhreaLenlng 3lu has been used ln con[uncLlon wlLh radlaLlon (comblned modallLy)
Lherapy before surgery (neoad[uvanL) as well as afLer surgery

SLage l (1
12
n
0
M
0
) recLal cancer paLlenLs do noL requlre ad[uvanL Lherapy due Lo Lhelr hlgh cure raLe wlLh surglcal
resecLlon Plghrlsk paLlenLs lncludlng Lhose wlLh poorly dlfferenLlaLed Lumor hlsLology and Lhose wlLh lymphovascular
lnvaslon should be consldered for ad[uvanL chemoLherapy and radloLherapy 1he new nCCn guldellnes recommend
comblnaLlon Lherapy wlLh lnfuslonal fluorouracll follnlc acld and oxallplaLln (lCLlCx) as reasonable for paLlenLs wlLh
hlghrlsk or lnLermedlaLerlsk sLage ll dlsease however lCLlCx ls noL lndlcaLed for good or averagerlsk sLage ll recLal
cancer
2728


aLlenLs wlLh locally advanced recLal cancer (1
34
n
0
M
0
or 1
any
n
12
M
0
) should recelve prlmary chemoLherapy and
radloLherapy 1he comblnaLlon of preoperaLlve radlaLlon Lherapy and chemoLherapy wlLh fluorouracll lmproves local
conLrol dlsLanL spread and survlval 1he basls of Lhls lmprovemenL ls belleved Lo be Lhe acLlvlLy of fluorouracll as a
radlosenslLlzer Surglcal resecLlon can be done 4 Lo 10 weeks afLer compleLlon of chemoLherapy and radloLherapy

use of lCLlCx or Lhe comblnaLlon of follnlc acld fluorouracll and lrlnoLecan (lCLll8l) ls recommended ln LreaLmenL of
paLlenLs wlLh sLage lll or lv dlsease CeLuxlmab should noL be used ln paLlenLs wlLh Lhe kkA5 muLaLlon
29
ln recenL
randomlzed phase lll sLudles panlLumumab a monoclonal anLlbody for LCl8 comblned wlLh lCLlCx4 (fluorouracll
leucovorln and oxallplaLln) or lCLll8l (fluorouracll leucovorln and lrlnoLecan) slgnlflcanLly lmproved progresslonfree
survlval when compared Lo lCLlCx4 or lCLll8l alone ln paLlenLs wlLh meLasLaLlc colorecLal cancer and wlldLype k8AS
sLaLus
3031


Stag|ng and treatment kecta| cancer treatment a|gor|thm (Surgery fo||owed by ad[uvant chemotherapy and
rad|otherapy) n|t|a| stages are Lndorecta| u|trasound stag|ng (u1)


1able 3 ColorecLal ChemoLherapeuLlc 8eglmens
CLN AND kLC1AL CANCLk
CMMN CnLM1nLkA kLGMLNS
LO
(every 2 weeks)
CxallplaLln 83 mg/m
2
day 1
Leucovorln 200 mg/m
2
day 1
3lu 400 mg/m
2
lv 8olus day 1 and 2
3lu 600 mg/m
2
lv lnfuslon day 1 and 2 (22 hours)
LO 4
(every 2 weeks)
(4 cyc|es)
CxallplaLln 83 mg/m
2
day 1
Leucovorln 200 mg/m
2
day 1
3lu 400 mg/m
2
lv 8olus day 1 and 2
3lu 2400 mg/m
2
lv lnfuslon day 1 (46 hours)
mLO 6
(Lvery 2 weeks)
(4 cyc|es)
CxallplaLln 83 mg/m
2
day 1
Leucovorln 400 mg/m
2
day 1
3lu 400 mg/m
2
lv 8olus day 1 and 2
3lu 1200 mg/m
2
lv lnfuslon day 2 days
CapeO
(1w|ce da||y x 14 days)
(every 3 weeks)
CxallplaLln 130 mg/m
2
day 1
CapeclLablne 830 mg/m
2
C 8lu for 14 days
Lk
(every 2 weeks)
lrlnoLecan 163 mg/m
2
day 1
Leucovorln 200 mg/m
2
day 1
3lu 400 mg/m
2
lv 8olus day 1 and 2
3lu 600 mg/m
2
lv lnfuslon day 1 and 2 (22 hours)
LOk
(every 2 weeks)
lrlnoLecan 180 mg/m
2
day 1
CxallplaLln 83 mg/m
2
day 1
Leucovorln 200 mg/m
2
day 1
3lu 3200 mg/m
2
lv lnfuslon day (48 hours)
8evac|zumab 310 mg/kg lv every 2 weeks wlLh chemoLherapy
Cetux|mab 400 mg/m
2
lv day 1 Lhen 230 mg/m
2
lv weekly

Ad[uvant chemorad|at|on therapy

ln paLlenLs wlLh r sLage ll and lll resecLable recLal cancer preoperaLlve chemoradlaLlon enhances Lhe paLhologlcal
response and lmproves local conLrol however lL does noL lmprove elLher dlseasefree or overall survlval
32


kad|oembo||zat|on

A prospecLlve mulLlcenLer randomlzed phase lll sLudy by Pendllsz eL al compared Lhe addlLlon of yLLrlum90 resln Lo a
LreaLmenL reglmen of fluorouracll 300 mg/m
2
lv lnfuslon (days 114 q8wk) wlLh fluorouracll lv alone ?yLrlum90 was
ln[ecLed lnLraarLerlally lnLo Lhe hepaLlc arLery llndlngs showed LhaL Lhe addlLlon of radloembollzaLlon wlLh yyLrlum90
slgnlflcanLly lmproved Llme Lo llver progresslon and medlan Llme Lo Lumor progresslon
33

Med|cat|on
1he goals of pharmacoLherapy are Lo downsLage Lhe Lumor lnduce remlsslon reduce morbldlLy and prevenL
compllcaLlons
Ant|neop|ast|c agents
1he recommendaLlons from naLlonal Comprehenslve Cancer neLwork 13Lh Annual Conference are ouLllned as follows
1he use of as many chemoLherapy drugs as posslble ls recommended Lo maxlmlze Lhe effecL of ad[uvanL Lheraples for
colon and recLal cancer 8evaclzumab ln comblnaLlon wlLh chemoLherapy ls lndlcaLed ln paLlenLs wlLh poslLlve or
negaLlve resecLable synchronous meLasLases lor colon and recLal cancer bevaclzumab ln comblnaLlon wlLh
chemoLherapy ls also lndlcaLed ln paLlenLs wlLh unresecLable synchronous meLasLases lCLlCx a comblnaLlon of
follnlc acld fluorouracll and oxallplaLln ls reasonable Lo use for hlghrlsk or lnLermedlaLerlsk sLage ll paLlenLs (see
1able 3)

lCLlCx ls noL lndlcaLed for goodrlsk or averagerlsk sLage ll paLlenLs ln paLlenLs ln whom 3fluorouracll LreaLmenL has
falled capeclLablne should be avolded aLlenLs who experlence no beneflL from bevaclzumab reglmens should avold
conLlnulng Lhe Lherapy CeLuxlmab should noL be replaced wlLh panlLumumab aLlenLs wlLh kkA5 muLaLlons should
noL be LreaLed wlLh ceLuxlmab or panlLumumab as Lhese muLaLlons confer reslsLance Lo epldermal growLh facLor
recepLor (LCl8) lnhlblLors
|uorourac|| (SU |uorourac|| Adruc||)
8locks meLhylaLlon of deoxyurldyllc acld Lo Lhymldyllc acld Lhereby lnLerferlng wlLh unA synLhesls uose ls bodywelghL
dependenL and varles wlLh speclflc proLocol ln whlch paLlenL ls lnvolved
Dos|ng
Adu|t
noL Lo exceed 800 mg/d lv
ed|atr|c
noL esLabllshed
nteract|ons
AnLlcoagulanLs nSAlus plaLeleL lnhlblLors and LhrombolyLlc agenLs lncrease rlsk of bleedlng oLher
lmmunosuppresslve agenLs exacerbaLe bone marrow LoxlclLy
Contra|nd|cat|ons
uocumenLed hypersenslLlvlLy bone marrow suppresslon serlous lnfecLlon Loplcal admlnlsLraLlon pregnancy
recaut|ons
regnancy
u unsafe ln pregnancy
recaut|ons
nausea oral and Cl ulcers depresslon of lmmune sysLem and hemopolesls fallure (bone marrow suppresslon) may
occur ad[usL dosage ln renal lmpalrmenL

V|ncr|st|ne (V|ncasar S ncov|n)
Mechanlsm of acLlon uncerLaln May lnvolve decrease ln reLlculoendoLhellal cell funcLlon or lncrease ln plaLeleL
producLlon lL ls mlLoLlc splndle lnhlblLor
Dos|ng
Adu|t
uose deLermlned by oncologlsL lnvolved noL rouLlnely used Lo LreaL recLal cancer
ed|atr|c
noL esLabllshed
nteract|ons
MlLomyclnC may cause acuLe pulmonary reacLlon
Contra|nd|cat|ons
uocumenLed hypersenslLlvlLy
recaut|ons
regnancy
u unsafe ln pregnancy
recaut|ons
CauLlon ln paLlenLs wlLh severe cardlopulmonary or hepaLlc lmpalrmenL or preexlsLlng neuromuscular dlsease

Leucovor|n (We||covor|n)
oLenLlaLes effecLs of fluorouracll 8educed form of follc acld LhaL does noL requlre enzymaLlc reducLlon reacLlon for
acLlvaLlon Allows for purlne and pyrlmldlne synLhesls boLh of whlch are needed for normal eryLhropolesls
Clven [usL prlor Lo fluorouracll
Dos|ng
Adu|t
uose deLermlned by predeLermlned doslng reglmen of fluorouracll
ed|atr|c
noL esLabllshed
nteract|ons
none reporLed
Contra|nd|cat|ons
uocumenLed hypersenslLlvlLy pernlclous anemla vlLamlndeflclenL megaloblasLlc anemlas
recaut|ons
regnancy
C SafeLy for use durlng pregnancy has noL been esLabllshed
recaut|ons
uo noL admlnlsLer lnLraLhecally or lnLravenLrlcularly

r|notecan (Camptosar Camptothec|n11 C111)
lnhlblLs Lopolsomerase l lnhlblLlng unA repllcaLlon and consequenLly cell prollferaLlon
Dos|ng
Adu|t
uose depends on proLocol ln whlch paLlenL ls lnvolved
ed|atr|c
noL esLabllshed
nteract|ons
ConcomlLanL admlnlsLraLlon wlLh oLher anLlneoplasLlcs may resulL ln prolonged neuLropenla LhrombocyLopenla and
lncreased morbldlLy/morLallLy raLes
Contra|nd|cat|ons
uocumenLed hypersenslLlvlLy bone marrow suppresslon renal funcLlon lmpalrmenL
recaut|ons
regnancy
u unsafe ln pregnancy
recaut|ons
Adverse effecLs lnclude myelosuppresslon dermaLlLls nausea and vomlLlng monlLor bone marrow funcLlon

xa||p|at|n (L|oxat|n)
A plaLlnumbased anLlneoplasLlc agenL used ln comblnaLlon wlLh an lnfuslon of 3fluorouracll (3lu) and leucovorln for
Lhe LreaLmenL of meLasLaLlc colorecLal cancer ln paLlenLs wlLh recurrence or progresslon followlng lnlLlal LreaLmenL wlLh
lrlnoLecan 3lu and leucovorln lL forms lnLersLrand and lnLrasLrand LunA crossllnks LhaL lnhlblL unA repllcaLlon and
LranscrlpLlon 1he cyLoLoxlclLy ls cellcycle nonspeclflc
Dos|ng
Adu|t
uay 1 83 mg/m
2
lv over 2 h admlnlsLer slmulLaneously wlLh leucovorln 200 mg/m
2
followed by 3lu 400 mg/m
2
lv
bolus over 24 mln Lhen 3lu 600 mg/m
2
lv conLlnuous lnfuslon ln 300 mL u3W over 22 h
uay 2 Leucovorln 200 mg/m
2
lv over 2 h followed by 3lu 400 mg/m
2
lv bolus over 24 mln Lhen 3lu 600 mg/m
2
lv
as a conLlnuous lnfuslon ln 300 mL u3W over 22 h
ed|atr|c
noL esLabllshed
nteract|ons
May lncrease 3lu serum concenLraLlon by approxlmaLely 20
Contra|nd|cat|ons
uocumenLed hypersenslLlvlLy Lo oxallplaLln or oLher plaLlnum compounds
recaut|ons
regnancy
u unsafe ln pregnancy
recaut|ons
Anaphylaxls may occur wlLhln mlnuLes of admlnlsLraLlon may cause neuropaLhy pulmonary flbrosls bone marrow
suppresslon Cl LracL sympLoms (eg nausea vomlLlng sLomaLlLls) renal or hepaLlc LoxlclLy (decrease dose) or
Lhromboembollsm dlluLe lv only ln dexLroseconLalnlng soluLlon

Cetux|mab (Lrb|tux)
8ecomblnanL human/mouse chlmerlc monoclonal anLlbody LhaL speclflcally blnds Lo Lhe exLracellular domaln of human
epldermal growLh facLor recepLors (LCl8 PL81 cLrb81) CeLuxlmabbound LCl recepLor lnhlblLs acLlvaLlon of
recepLorassoclaLed klnases resulLlng ln lnhlblLlon of cell growLh lnducLlon of apopLosls and decreased producLlon of
maLrlx meLalloproLelnase and vascular endoLhellal growLh facLor lndlcaLed for LreaLlng lrlnoLecanrefracLory LCl8
expressed meLasLaLlc colorecLal carclnoma 1reaLmenL ls preferably comblned wlLh lrlnoLecan May be admlnlsLered as
monoLherapy lf lrlnoLecan ls noL LoleraLed
Dos|ng
Adu|t
llrsL dose 400 mg/m
2
lv lnfused over 2 h
Weekly malnLenance doses 230 mg/m
2
lv lnfused over 1 h
noL Lo exceed lnfuslon raLe of 10 mg/mln (le 3 mL/mln) musL admlnlsLer wlLh lowproLelnblndlng 022 m lnllne
fllLer premedlcaLlon wlLh an P1 anLagonlsL (eg dlphenhydramlne 30 mg lv) recommended
ed|atr|c
noL esLabllshed
nteract|ons
LlmlLed daLa exlsL none reporLed
Contra|nd|cat|ons
none reporLed
recaut|ons
regnancy
C SafeLy for use durlng pregnancy has noL been esLabllshed
recaut|ons
CauLlon wlLh documenLed hypersenslLlvlLy lncludlng allergy Lo murlne proLelns may cause lnfuslonrelaLed
hypoLenslon and alrway dlsLress (eg bronchospasm sLrldor hoarseness) parLlcularly wlLh Lhe flrsL lnfuslon (90)
premedlcaLe wlLh dlphenhydramlne 30 mg lv decrease dose wlLh mlld or moderaLe (grade 1 or 2) lnfuslon reacLlon and
lmmedlaLely and permanenLly dlsconLlnue wlLh severe (grade 3 or 4) lnfuslon reacLlon common adverse effecLs lnclude
acnellke rash dry skln Llredness or weakness fever consLlpaLlon and abdomlnal paln may rarely cause lnLersLlLlal
lung dlsease do noL shake or dlluLe soluLlon sunllghL can exacerbaLe any skln reacLlons

8evac|zumab (Avast|n)
lndlcaLed as a flrsLllne LreaLmenL for meLasLaLlc colorecLal cancer Murlnederlved monoclonal anLlbody LhaL lnhlblLs
anglogenesls by LargeLlng and lnhlblLlng vascular endoLhellal growLh facLor (vLCl) lnhlblLlng new blood vessel
formaLlon denles blood oxygen and oLher nuLrlenLs needed for Lumor growLh used ln comblnaLlon wlLh sLandard
chemoLherapy
Dos|ng
Adu|t
3 mg/kg lv q2wk unLll dlsease progresslon deLecLed
ed|atr|c
noL esLabllshed
nteract|ons
CoadmlnlsLraLlon wlLh 3fluorouracll lncreases frequency (2fold) of serlous and faLal arLerlal Lhromboembollc evenLs
(le CvA Ml 1lAs anglna)
Contra|nd|cat|ons
none reporLed
recaut|ons
regnancy
C SafeLy for use durlng pregnancy has noL been esLabllshed
recaut|ons
Anglogenesls ls crlLlcal Lo feLal developmenL and use of bevaclzumab durlng pregnancy llkely resulLs ln adverse feLal
effecLs common adverse effecLs lnclude hyperLenslon faLlgue Lhrombosls dlarrhea leukopenla proLelnurla
headache anorexla and sLomaLlLls may cause serlous or faLal (buL rare) evenLs lncludlng gasLrolnLesLlnal LracL
perforaLlon lnLraabdomlnal lnfecLlons lmpalred wound heallng hemopLysls (parLlcularly wlLh lung cancers) and
lnLernal bleedlng lncreases rlsk of serlous and faLal arLerlal LhromboLlc evenLs wlLh 3fluorouracll do noL lnlLlaLe
LreaLmenL for aL leasL 28 d afLer ma[or surgery (Lhe surglcal lnclslon should be fully healed) breasLfeedlng should be
dlsconLlnued durlng and for aL leasL 20 d afLer LreaLmenL wlLh bevaclzumab


an|tumumab (Vect|b|x)
8ecomblnanL human lgC2 kappa monoclonal anLlbody LhaL blnds Lo human epldermal growLh facLor recepLor (LCl8)
lndlcaLed Lo LreaL colorecLal cancer LhaL has meLasLaslzed followlng sLandard chemoLherapy
Dos|ng
Adu|t
6 mg/kg lv lnfused over 60 mln q2wk
ed|atr|c
noL esLabllshed
nteract|ons
uaLa llmlLed none reporLed
Contra|nd|cat|ons
none known
recaut|ons
regnancy
C SafeLy for use durlng pregnancy has noL been esLabllshed
recaut|ons
Common adverse effecLs lnclude rash faLlgue abdomlnal paln nausea and dlarrhea serlous adverse effecLs lnclude
pulmonary flbrosls severe rash compllcaLed by lnfecLlons lnfuslon reacLlons (for grade l or ll reacLlon reduce lnfuslon
raLe by 30 for grade lll or lv reacLlon lmmedlaLely dlsconLlnue permanenLly) ocular LoxlclLy abdomlnal paln
vomlLlng and consLlpaLlon admlnlsLer uslng lowproLelnblndlng fllLer
Vacc|ne
Pv ls assoclaLed wlLh abouL 90 of anal cancer ln a sLudy of homosexual males Pv vacclne was shown Lo be 78
effecLlve ln prevenLlon of Pv 16 and 18relaLed anal lnLraeplLhellal neoplasms

ap|||omav|rus vacc|ne
CuadrlvalenL human paplllomavlrus (Pv) recomblnanL vacclne vacclne efflcacy medlaLed by humoral lmmune
responses followlng lmmunlzaLlon serles lndlcaLed for prevenLlon of anal cancer and assoclaLed precancerous leslons
caused by Pv Lypes 6 11 16 and 18 people aged 926 years
Dos|ng
Adu|t
26 years 03 mL lM admlnlsLered as 3 separaLe doses admlnlsLer second and Lhlrd doses 2 and 6 mo afLer flrsL dose
respecLlvely
26 years noL esLabllshed
ed|atr|c
9 years noL esLabllshed
9 years AdmlnlsLer as ln adulLs
nteract|ons
lmmunosuppresslve Lheraples (eg lrradlaLlon anLlneoplasLlc agenLs corLlcosLerolds) may decrease lmmune response
Lo vacclne
Contra|nd|cat|ons
uocumenLed hypersenslLlvlLy
recaut|ons
regnancy
8 leLal rlsk noL conflrmed ln sLudles ln humans buL has been shown ln some sLudles ln anlmals
recaut|ons
Shake well before admlnlsLerlng admlnlsLer ln delLold reglon of upper arm or ln hlgher anLerolaLeral Lhlgh lndlvlduals
wlLh lmpalred lmmune responslveness (eg Plv lnfecLlon neoplasLlc dlsease currenLly Laklng lmmunosuppresslve
drugs) may noL ellclL anLlbody response because of lM admlnlsLraLlon do noL admlnlsLer Lo lndlvlduals wlLh bleedlng
dlsorders (eg LhrombocyLopenla coagulaLlon dlsorders anLlcoagulanL Lherapy) common adverse effecLs lnclude paln
swelllng eryLhema and/or prurlLus aL ln[ecLlon slLe and fever
o||owup
Deterrence]revent|on
Cn uecember 22 2010 Lhe uS lood and urug AdmlnlsLraLlon approved Lhe use of quadrlvalenL human papllloma vlrus
(Pv) vacclne (Cardasll) for prevenLlon of anal cancer and assoclaLed precancerous leslons ln people aged 926 years
Pv ls assoclaLed wlLh abouL 90 of anal cancer ln a sLudy of homosexual males Pv vacclne was shown Lo be 78
effecLlve ln prevenLlon of Pv 16 and 18relaLed anal lnLraeplLhellal neoplasms
rognos|s
Cverall 3year survlval raLes for recLal cancer are as follows
O SLage l 90
O SLage ll 60 Lo 83
O SLage lll 27 Lo 60
O SLage lv 3 Lo 7
llfLy percenL of paLlenLs develop recurrence whlch may be local dlsLanL or boLh
Local recurrence ls more common ln recLal cancer Lhan ln colon cancer
O ulsease recurs ln 330 of paLlenLs usually ln Lhe flrsL year afLer surgery
O lacLors LhaL lnfluence Lhe developmenL of recurrence lnclude surgeon varlablllLy grade and sLage of Lhe
prlmary Lumor locaLlon of Lhe prlmary Lumor and ablllLy Lo obLaln negaLlve marglns
O Surglcal Lherapy may be aLLempLed for recurrence and lncludes pelvlc exenLeraLlon or A8 ln paLlenLs who had
a sphlncLersparlng procedure
O 8adlaLlon Lherapy generally ls used as palllaLlve LreaLmenL ln paLlenLs who have locally unresecLable dlsease