Esp i No Celular

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JEADVDOI: 10.1111/j.1468-3083.2011.04296.x Bonerandi et a.1

! 2011 "#e A$t#or%

Jo$rna o& t#e E$ro'ean A(ade)* o& Der)atoo+* and Venereoo+*! 2011 E$ro'ean A(ade)* o& Der)atoo+* and Venereoo+*JEADV 2011, 2 $''. , 11! 2011 "#e A$t#or%

Jo$rna o& t#e E$ro'ean A(ade)* o& Der)atoo+* and Venereoo+*! 2011 E$ro'ean A(ade)* o& Der)atoo+* and Venereoo+*JEADV 2011, 2 $''. , 11

IDEI5E

$ideine% &or t#e dia+no%i% and treat)ent o& ($taneo$%

%$a)o$% (e (ar(ino)a and 're($r%or e%ion%

J.J. Bonerandi,7 . Bea$iain, . a$ant,; J.. ae?re,77

. De%o$(#e%, a%ti( $r+er*, "o$o$%e nier%it* o%'ita, "o$o$%e, aradoxi(a*, a% t#e* are not +enera* re(orded in (an(er

re+i%ter%, t#eir i)'ortan(e in ter)% o& '$i( #eat# and t#eir

e(ono)i( i)'a(t on #eat#(are %*%te)% are Gide*

$ndere%ti)ated.

"#e%e 'ro&e%%iona re(o))endation% #ae re(eied t#e joint I5A-

A +$arantee o& $ait*, G#i(# %i+ni&ie% t#at t#e +$ideine% #ae een

(reated a((ordin+ to t#e 'ro(ed$re% and )et#odoo+i(a r$e% re(o)-

)ended * t#e I5A and t#e A. An* $erie% re+ardin+ t#e (ontent

%#o$d e addre%%ed to t#e %'on%or.

"#e%e +$ideine% #ae een draGn $' at t#e re$e%t o& t#e


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a((ordin+ to G#et#er t#era'* #a% een %'e(i&i(a* (odi&ied or

not. In addition, t#e ter)inoo+* $%ed to de%(rie t#e%e e%ion%

arie%, G#i(# )a* ead to (on&$%ion and 'reent $%e o& a (ear

de(i%ion- )aHin+ tree.

"#e "5@ (a%%i&i(ation, deeo'ed * AJL IA L

I, G#i(# i% $%ed &or a %Hin (an(er% ex(e't )eano)a, i% not

%$itae &or . It doe% not taHe into a((o$nt t#e )$ti'e

'ro+no%ti( (riteria identi&ied in t#e iterat$re.

@an* treat)ent% are ($rrent* aaiae, in 'arti($ar, &or

're($r%or e%ion%, $t t#e (riteria o& (#oi(e and t#e

)et#od% o& a''i(ation are +enera* &ar &ro) (ear &or

'ra(titioner%. "#i% re%$t% in )ajor di%'aritie% in ter)% o&

t#era'e$ti( )ana+e)ent.

"#e 're%ent +$ideine% dea Git# t#e treat)ent o& and

're- ($r%or e%ion% in i))$no(o)'etent ad$t% in ra(ti(e in a((ordan(e Git# t#e ADA>"E

)et#od.2

A% it% na)e %$++e%t%, t#i% )et#od ado(ate% t#e

ada'tation to a 'arti($ar %it$ation in t#i% (a%e, )edi(a

'ra(ti(e in

er%'e(tie%

%e(tion.

I.2. Detai% o& t#e dra&tin+ 'ro(e%% &or t#e +$ideine%

I.2.1. ADA>"E )et#od "#i% ri+oro$% and ex'i(it )et#od,

re(ent* de%(ried and '$i%#ed * an internationa +ro$',2,3

i% de%i+ned to enae t#e ada'tation o& exi%tin+ +$ideine%, and

to red$(e t#e ti)e, e&&ort and (o%t re$ired to (reate a &re%# %et

o& +$ideine%. @et#odoo+i(a +$ideine% (on(ernin+ t#e $%e o&

t#i% )et#od Gere '$i%#ed onine * A in @ar(# 200R.3

I.2.2. #oi(e o& )et#od &or dra&tin+ +$ideine% In t#e %'rin+

o& 200R, t#e "E )et#od (o$d e $%ed to dra&t


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$ideine% &or ($taneo$% and 're($r%or e%ion% 3Bonerandi et a.3

od, Gere aread* HnoGn, and ADA>"E (ontext$aiKation Ga%

entire* 'o%%ie, a% t#e%e +$ideine% #ad een '$i%#ed *

a+en- (ie% or )edi(a %o(ietie% &or 'o'$ation% and ee% o&

#eat# in&ra- %tr$(t$re and or+aniKation (o)'arae Git# t#o%e in

"E

)et#od 're- %ented a n$)er o& i)itation%. In addition to t#i%,

%eera $e%- tion% t#at #ae %$%e$ent* (o)e to t#e &ore e.+.

t#e nat$re o& A or t#e 'a(e o& neG )edi(a treat)ent%

o(($'ied itte or no 'a(e in t#e exi%tin+ +$ideine%. "#ere&ore,

in addition to ada'tation, $'datin+ o& t#e iterat$re 'roed

ne(e%%ar*.

I.2.3. De&inition o& t#e %(o'e o& t#e +$ideine% "#e i)it% o&

t#e to'i( Gere di%($%%ed in (on&eren(e (a% etGeen

)e)er% o& t#e O in J$* 200R. "#e >I>O (#e(Hi%t3

$%ed to

de&ine t#e %(o'e and tar+et a$dien(e o& t#e +$ideine% Ga% a%

&ooG%:

M > 'atient 'o'$ation S %, o(($'ationa t#era'i%t% a% Ge a% %'e(iai%t%

inoed in t#e %(reenin+ and &ooG-$'N

M O o$t(o)e%, t#e ea$ation (riteria $%ed &or t#e re(o)-

)endation% S ee% o& treat)ent re%'on%e in ter)% o&

re)i%%ion, o(a rea'%e, re)ote )eta%ta%i% and )ortait*,

G#en t#e%e 'ara)eter% Gere aaiaeN

M #eat#(are %ettin+ S a)$ator* or #o%'ita.

In addition to dia+no%i% and ($ratie treat)ent o& , it

Ga% de(ided to in($de:

M %(reenin+ o& %$je(t% identi&ied a% at ri%H &or ex($d-

in+ +enoder)ato%i% and i))$node're%%ionN

M ($taneo$% or ($taneo$%-)$(o%a %ite% on t#e orderine

o& der)atoo+*: e*eid% and er)iion order o& t#e i'%N

M e%ion% (on%idered 're(an(ero$% and Heratoa(ant#o)a.

"#e%e e%ion% are #i%to+eneti(a* reated to and #ae

een deat Git# in %eera re(ent %t$die% o& )edi(a and

%$r+i(a t#era'ie%.

oGeer, +enita and ana %ite% in ot# +ender% Gere r$ed

o$t a% t#e%e are nor)a* deat Git# * +*nae(oo+i(a %$r+eon%,

$roo- +i%t%, +a%troenteroo+i%t% or di+e%tie %$r+eon%. n+$a

%ite% Gere %i)iar* r$ed o$t. In addition, it Ga% de(ided not toin($de o%ered in i))$no%$''re%%ed or+an tran%'ant

re(i'ient%, a% +$ideine% &or t#e )ana+e)ent o& t#e%e 'atient%

Gere ein+ draGn $' $nder t#e a$%'i(e% o& t#e A.4

I.2.4. Do($)entar* re%ear(# In ate J$ne to ear* J$* 200R,

@r% J. Br$+nea$x 'er&or)ed a iterat$re %ear(# &or 'ra(ti(a

+$ideine% on and 're($r%or e%ion% $%in+ %*%te)ati(

%$re*% o& )edi(a iio+ra'#* dataanH% Annex 3 and

ooHin+ o$t &or +$ideine%, (on%en%$% (on&eren(e%, arti(e% on

de(i%ion-)aHin+ 'ro(e%%, %*%te)ati( reieG%, )eta-ana*%e% and

ot#er nationa and

internationa ea$ation %t$die%. Ceeant Ge%ite% +oern)ent

a+en(ie%, )edi(a %o(ietie%, et(. Gere a%o ex'ored. Do($)ent%

not a((e%%ie * t#e %tandard di&&$%ion (ir($it% T+re*

iterat$re Gere (on%$ted $%in+ eer* aaiae )ean%. e+a

and re+$ator* text% on t#i% %$je(t Gere a%o (on%$ted. On*

En+i%#- and a%ti( $r+eon%. 2002 BADL BA>,

3 $ideine% &or )ana+e)ent o& BoGen% di%ea%e: 2006 $'date.

Briti%# A%%o(iation o& Der)atoo+i%t%. 2006 BAD, .

4 $ideine% &or t#e )ana+e)ent o& a(tini( Herato%i%.

Briti%# A%%o(iation o& Der)atoo+i%t%. 200R BAD, .

Ba%a (e and %$a)o$% (e %Hin (an(er%.

5ationa o)'re#en%ie an(er 5etGorH. 200R 55,

.

6 @$ti'ro&e%%iona +$ideine% &or t#e )ana+e)ent o& t#e'atient Git# 'ri)ar* %$a)o$% (e (ar(ino)a.

5ationa $ideine earin+#o$%e. 200R 5, .

R reen A, @arH% C. $a)o$% (e (ar(ino)a o& t#e %Hin

non-)eta%tati(. in Eid 200N 4: 20862090.

I.2.6. ee(tion o& +$ideine% &or ada'tation "#e %$itaiit* o&

t#e%e %een +$ideine% &or ada'tation in di&&erent area% o&

'ra(ti(e Ga% a%%e%%ed * &ie Q, $%in+ t#e %i)'i&ied ACEE

a''rai%a in%tr$)ent

Annex 4.

"#e 5 +$ideine% and t#e ini(a Eiden(e arti(e

Gere not $%ed, a% t#e &or)er i% a retran%(ri'tion o& t#e BAD

2002


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+$ideine%, G#erea% t#e atter +ie% no indi(ation o& t#e

)et#od $%ed &or t#e iio+ra'#* %ear(#, and Ga% t#$% dee)ed

in(on%i%- tent Git# t#e %(o'e o& t#e 're%ent +$ideine%.

"#e &ooGin+ t#ree +$ideine% Gere $ti)ate* %ee(ted:

M Ba%a (e and %$a)o$% (e %Hin (an(er%, 200R 55N

M @$ti'ro&e%%iona +$ideine% &or t#e )ana+e)ent o& t#e

'atient Git# 'ri)ar* ($taneo$% %$a)o$% (e (ar(ino)a,

2002 BAD 2002N

M 5on-)eano)a %Hin (an(er: +$ideine% &or treat)ent and

)ana+e)ent in A$%traia, 2002 5@C, to+et#er Git#

$ideine% &or t#e )ana+e)ent o& a(tini( Herato%e%, 200R

BAD 200R and $ideine% &or )ana+e)ent o& BoGen%

di%ea%e: 2006 BAD 2006.

I.2.R. a*o$t o& t#e +$ideine%, He* 'oint% and re(o))en-

dation% Ea(# %e(tion Ga% diided into Tite)%J, %o)e o& G#i(#

(ontained one or )ore THe* 'oint% or Tre(o))endation%. An

ite) Ga% (o)'ri%ed o& a to'i( (on(ernin+ e'ide)ioo+*,

dia+no%i% or treat)ent a)enae to tar+eted do($)entar*re%ear(# e.+. 'reaen(e o& a)on+ t#e ": d*na)i( '#otot#era'*N A:

V:

#$)an 'a'io)air$%N ID: interdi%(i'inar* (on%$tationN

IE":

'o%itron e)i%%ion to)o+ra'#*N >5I: 'erine$ra ina%ionN

C": radiot#era'*N


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"ae 1 *no'%i%: ite)% in($ded in ada'ted +$ideine%

ini(a &eat$re% o& A W W

i%too+* o& A W W

5o%oo+* o& A

E'ide)ioo+* o& A W W

ini(a &eat$re% o& BD W W

i%too+* o& BD W W

5o%oo+* o& BD W

E'ide)ioo+* o& BD W

>reention o& A and BD W W W

$r+er* &or A and BD W W

r*ot#era'* W W W W

$retta+e W W W W

a%er O2 W W W

-#otod*na)i( t#era'* >D" W W W W

Cetinoid% W W W

Cadiot#era'* &or A, BD W W

E'ide)ioo+* o& W W

ini(a &eat$re% o& W W

Variant% o& W

ini(a'ro+no%i% o& W W W

i%too+i(a 'ro+no%i% o& W W W

>ro+no%ti( (a%%i&i(ation W

@eta%ta%e% o& W W

>reention o& W W W

$r+er* &or W W W

@i(ro+ra'#i( %$r+er* &or W W W

$retta+e &or W W

$r+er* &or )eta%ta%e% W W W

Cadiot#era'* &or W W W

#e)ot#era'* &or W

(reenin+ &or A, BD, and W W W

i%to'at#oo+* o& W W

tandardiKed #i%too+* re'ort W

i%to'at#oo+* o& *)'# node%

Initia %ta+in+ o& W

Ine%ti+ation )et#od%

@onitorin+ o& W W

"reat)ent o& a((ordin+ to 'ro+no%i%

"reat)ent o& *)'# node )eta%ta%i% W

"reat)ent o& re)ote )eta%ta%i% W

eratoa(ant#o)a W

i%too+* o& Heratoa(ant#o)a W

5o%oo+* o& Heratoa(ant#o)a W

E'ide)ioo+* o& Heratoa(ant#o)a

$r+er* &or Heratoa(ant#o)a W

@edi(a treat)ent &or Heratoa(ant#o)a W

Biio+ra'#i(a re&eren(e% BAD 2002 5@C 2002 55 200R BAD 2006 BD BAD 200R A

194R2001 1912001 19642006 1961200 19682006


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ada'ted +$ideine%, i.e. t#e t#ree +$ideine% dedi(ated to

5@C,R

558

and BAD9 and t#o%e %'e(i&i(a* &o($%ed

on A and BD,10,11

re%tri(t t#e)%ee% to a %$))ar*

de%(ri'tion o& t#e%e entitie% Git#o$t di%($%%in+ (ini(o-

anato)i(a &or)% and no)en(at$re. "#e Q &et it Ga%

ne(e%%ar* to ado't a 'o%ition on t#i% %$je(t and t#ere&ore, t#e

ADA>"E )et#od Ga% not $%ed in dra&tin+ t#i% (#a'ter, &or

G#i(# a %'e(i&i( iio+ra'#i(a ana*- %i% Ga% 'er&or)ed. "#i%

(#a'ter (ontain% e'ide)ioo+i(a oer- ieG% and 'ro'o%a% Git#

re+ard to ter)inoo+* and (a%%i&i(ation. It a%o de%(rie% t#e

'o'$ation% tar+eted * t#e%e +$ideine%.

II.1. Ci%H &a(tor% &or and 're($r%or e%ion%

II.1.1. Eniron)enta &a(tor% Ex'o%$re to %$n $ni+#t i% t#e

'rin(i'a eniron)enta &a(tor, and eiden(e &or it% roe in

reie% on t#e a''earan(e o& e%ion% on t#e area% o& %Hin )o%t

ex'o%ed to %$n, a +reater 'reaen(e o& e%ion% a)on+ &air-

%Hinned %$je(t%, a atit$de +radient &or 'o'$ation% Git# t#e%a)e %Hin '#otot*'e and a #i+#er in(iden(e o& t#e di%ea%e

a)on+ 'atient% GorHin+ o$tdoor%.12

"#e o(($rren(e o& i%

a%%o(iated Git# tota ($)$atie i&eti)e V do%e. "#e )o%t

(o))on* a&&e(ted %ite% in($de t#e &a(e, a(H o& t#e #and% and

&orear)%. In a 'ani%# %t$d*, )ore t#an 92X o& (a%e%

o(($rred in t#e%e area%.13

VB 290320 n) and VA 320400 n) 'a* a roe in

(ar(i- no+ene%i%. 3 +ene.14

Arti&i(ia %o$r(e% o& V #ae a%o een in(ri)inated.1 >VA

t#era'* in ex(e%% o& 200 %e%%ion% i% a%%o(iated Git# t#e on%et

o& . o$r(e% o& t#i% t*'e o& radiation in tannin+ %aon% are

not #ar)e%% and )$%t e added to ot#er ri%H &a(tor%.16

A((ordin+ to t#e 200 re'ort * t#e V

a%o o(($r% in extra+enita re+ion% in t#e (a%e o& BD, in area%

t#at are


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ot# ex'o%ed and $nex'o%ed to %$ni+#t and in

i))$node're%%ed and i))$no(o)'etent 'atient% aiHe.2023

oGeer, t#e 're%en(e o& >V aone i% in%$&&i(ient to ind$(e

(e$ar 'roi&eration. "#ree ri%H &a(tor% are &o$nd in or+an

+ra&ted 'atient%: %$n ex'o%$re, i)- )$node're%%ion and >V.

e* 'oint%

M $a)o$% (e (ar(ino)a %$%$)e% a n$)er o& )ai+nant

'ri)ar* e'it#eia %Hin t$)o$r% Git# )a'i+#ian di&&erentia-tion, and i% di%tin(t &ro) B.

M "#e He* &a(tor &ao$rin+ on%et o& , BoGen% di%ea%e

BD or a(tini( Herato%i% A i% t#e tota i&eti)e do%e o&

V re(eied, G#et#er nat$ra or arti&i(ia.

M "#e ri%H o& deeo'in+ A, BD or i% a&&e(ted * %Hin

'#otot*'e, G#i(# i% +eneti(a* deter)ined.

M A n$)er o& (o-(ar(ino+en%, G#i(# )a* e %'e(i&i( to 'ar-

ti($ar %ite%, #ae een identi&ied, %$(# a% toa((o &or a(tini(

(#eiiti% and o& t#e oGer i', a% Ge a% >V &or +enita

or ana .

M ertain )edi(a di%ea%e% a%o 'redi%'o%e to : (#roni(

in&a))ation, (#roni( Go$nd% and i))$node're%%ion.

II.2. >re($r%or% o&

II.2.1. A(tini( Herato%i%

II.2.1.1. ini(a, #i%too+i(a, e'ide)ioo+i(a a%'e(t% and nat$ra

#i%tor*

ini(a a%'e(t%

A(tini( Herato%i% (on%i%t% o& (o))on e%ion%, 'arti($ar* a)on+

i+#t-%Hinned %$je(t%, &o$nd in area% ex'o%ed to t#e %$n %$(# a%

t#e &a(e, t#e a(H o& t#e #and% and t#e %(a' in adin+

%$je(t%, and i% o&ten a%%o(iated Git# ot#er %i+n% o& #eioder)a

e.+. Grin- He%, &re(He%, et(.. Dia+no%i% i% $%$a* a%ed on t#e

(ini(a %ettin+, and i% %$++e%ted * &at, ro$+# e%ion% o&ar*in+ t#i(Hne%%, o((a%iona* )ore a''arent to t#e e*e t#an to

t#e to$(#, Git# a dia)eter o& aro$nd 1 () or e%%, Git#

ar*in+ de+ree% o& er*t#e)a, o((a%iona* 'i+)ented and

ad#e%ie *eoGi%# orroGni%# Heratin (oatin+.

In 'ra(ti(e, i%oated A or %)a n$)er% o& A are di%tin-

+$i%#ed &ro) )$ti'e A, G#i(# o((a%iona* (o)e to+et#er

to &or) 'a$e% %(a'. On t#e oGer i', a(tini( (#eiiti% i% t#e

aia e$iaent o& A. "#i% 'arti($ar di%order i% (#ara(teriKed

* t#e're%en(e o& toa((o %)oHin+ a% a %e(ond (ar(ino+eni(

&a(tor and* t#e )arHed )eta%tati( 'otentia o& in t#i% area.

i%too+i(aa%'e(t%

"#ere i% no %in+e #i%too+i(a a%'e(t o& A. "#ere )a* e

t#innin+ or #*'er'a%ia o& t#e e'ider)i%. "#e (ornea a*er i%

'ro'ortiona to e'ider)a t#i(Hne%%, and i% o((a%iona* er*

t#i(H (orn or (ao$%. An in&a))ator* rea(tion deeo'% on

(onta(t Git# t#e e'ider)i%, and t#ere i% &re$ent* a i(#enoid

a''earan(e.


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Dia+no%i% i% a%ed on t#e 're%en(e o& ario$% Heratino(*ti(

anor)aitie%: o%% o& 'oarit* a((o)'anied * (#an+e% in t#e

e'ider)a ar(#ite(t$re, at*'i(a (*ton$(ear &eat$re%, d*%Heratoti(

(e%, a(ant#o*%i% or a(ant#oHerato*%i%. In A, t#e%e

anor)aitie% o(($r in i%oation and do not inoe t#e entire

e'ider)i% or t#e %Hin a''enda+e%. "#e ter) (ar(ino)a in %it$ i%

on* $%ed G#en t#e%e anor)aitie% o(($r to+et#er in a

'rono$n(ed &a%#ion and a&&e(t t#e entire e'ider)a inin+. @o%t

re&eren(e GorH% )ention )or'#oo+i(a ariant% o& A:

'i+)ented, atro'#i(, #*'ertro'#i(, a(ant#o*ti( and i(#enoid.

"#e Q (on%ider% t#at t#e%e ariant% are %i)'* )inor

ariation% o& t#e %a)e entit* and, a% %$(#, do not )erit

(a%%i&i(ation a% di%tin(t &or)%.

>reaen(e, in(iden(e and nat$ra #i%tor*

"#e%e &i+$re% are not HnoGn &or V in t#eir

aetio'at#o- +ene%i%.

A Geat# o& +*nae(oo+i(a iterat$re #a% e%tai%#ed t#e (on(e't

o& $ar and %$%e$ent* 'enie intrae'it#eia neo'a%ia

VI5 and >I5 a% Ge a% (eri(a intrae'it#eia neo'a%ia I5.

At*'i- (a (a%e% o%ered are %e)i-$anti&ied $nder t#e ter)

VI5 or >I5 or I5 I, II or III, a((ordin+ to G#et#er t#e*

inoe t#e oGer t#ird, tGo-t#ird% or )ore t#an tGo-t#ird% o&

t#e e'it#eia t#i(Hne%%. Q#en t#e entire e'it#ei$) i% inoed,

t#e ter) intra- e'it#eia or BoGen% di%ea%e i% $%ed.

o(Here et a.2,26

%tre%% t#e anao+* etGeen A and

(eri(a

d*%'a%ia e%ion% and %$++e%t t#at t#e no)en(at$re o&

e'ider)a e%ion% A and BD %#o$d e #anded in t#e %a)e

Ga* a% t#eir (o$nter'art% in t#e +enita )$(o%a or %e)i-

)$(o%a, $%in+ t#e ter) I5 i.e. Heratino(*ti( intrae'ider)a

neo'a%ia.

"#e Q &et t#at t#ere Ga% itte a$e in %eeHin+ to $ni&*

#i%to- 'at#oo+i(a (riteria &or entitie% Git# dier+ent

aetio'at#o+ene%i% and (ini(a a%'e(t%. It t#ere&ore (on%idered

t#at t#ere Gere no +ro$nd% &or re'a(in+ t#e (ini(a na)e o&

A, re(o+niKed * t#e entire )edi(a (o))$nit*, Git# a

#i%to'at#oo+i(a na)e t#at i% e%% (ear to 'ra(titioner%.

i%to'at#oo+i%t% )a* neert#ee%% (ontin$e to +rade t#e eeo& e'it#eia d*%'a%ia% in t#eir re'ort%.

A:'re($r%or or %$a)o$% (e (ar(ino)aYR,8,10,2-28

"#i% di%tin(tion )i+#t a''ear to e '$re* a(ade)i(, Gere it not

&or it% %i+ni&i(ant i)'a(t in ter)% o& treat)ent and #eat#

in%$ran(e %o(ia %e($rit* rei)$r%e)ent, i&e in%$ran(e 're)i$)%,

et(..

>ro'onent% o& a $ni&ied ter)

29

(on%ider t#at a &or)% o& Aare in &a(t , to+et#er Git# BD, BoGenoid 'a'$o%i%, +iant

(on- d*o)a, err$(o$% (ar(ino)a, Heratoa(ant#o)a and

'roi&eratin+ tri(#ie))a (*%t%. A)on+ ot#er %#ared &eat$re%,

t#e%e entitie% are (#ara(teriKed * t#e exi%ten(e o& )$tation% in

on(o+ene >3.

oGeer, a n$)er o& e'ide)ioo+i(a %t$die% #ae e%tai%#ed

t#at t#e (o$r%e o& A )a* taHe t#ree di&&erent &or)%: %'ontaneo$%

di%a''earan(e, 'er%i%ten(e, or 'ro+re%%ion to . "#e 'ro+re%-

%ion rate &or A i% oG: In t#e A$%traian (o#ort %t$d* * @arH%

et a., (ited in t#e 5@C, t#e 'ro+re%%ion rate oer a -*ear &o-

oG-$' 'eriod Ga% oGer t#an 1L1000 'er *ear.30

"#e 55 +$ideine% (on%ider A a% '#otoind$(ed 're(an(er-

o$% e%ion%. oGeer, t#e 5@C and BAD +$ideine% do not

ado't a 'o%ition (on(ernin+ t#e nat$re o& A, %i)'* notin+ t#at

)o%t a''ear %$%e$ent to A,$t t#at t#e ri%H o& 'ro+re%-

%ion o& A to i% oG, t#$% j$%ti&*in+ t#e (#oi(e o& non-

ina- %ie to'i(a t#era'* &or )o%t A (a%e%.

an(eriKation &ied

Initia* de%(ried in reation to (ar(ino)a% o& t#e ora (ait*, a

(an(eriKation &ied denote% a re+ion (ontainin+ 'ret$)o$ra

anor)aitie%, and %$(ini(a and )$ti&o(a +eneti( )$tation%

(on%tit$tin+ t#e %ite o& neG 'ri)ar* t$)o$r% and o& o(a rea'%e.

Ce+ardin+ t#e %Hin, it #a% een (ear* e%tai%#ed t#at V

radiation i% a%%o(iated Git# t#e initiation, 'ro)otion and

'roi&eration %ta+e% o& (ar(ino+ene%i%. On(o+eneti(anor)aitie% #ae een %#oGn to e )ore (o))on in %$n-

ex'o%ed area% t#an in non- ex'o%ed area%.


9/56

er*t#ro'a%ia o& t#e 'eni% or e$Ho'a%ti(. enita &or)% are (o-

%e* a%%o(iated Git# >V.

i%to'at#oo+*

"#e e'ider)i% i% #*'er'a%ti(, Git# a di%or+aniKed ar(#ite(t$re

and at*'i(a Heratino(*te% o%% o& nor)a 'oarit*,

#*'er(#ro)at- i( n$(ei, ani%on$(eo%i%, )ito%e% and

d*%Herato%i%, 're%ent at a ee%, at#o$+# * de&inition, t#e*

do not (ro%% t#e a%a )e)-rane. Variant% o& BD Git# (ear,

'a+etoid or 'i+)ented (e% #ae een de%(ried, and

i))$no#i%to(#e)i%tr* )a* e re$ired to deter)ine G#et#er

t#e* are )a'i+#ian.

In t#e 'erinea area%, di&&erentia dia+no%i% Git# BoGenoid

'a'- $o%i% VI5 3, >I5 3 i% a%ed 'ri)ari* on ti)e o& on%et,

(ini(a a''earan(e, )edi(a #i%tor*, 're%en(e o& #i%too+i(a

%i+n% o& ira (*to'at#o+eni( e&&e(t and, in (ertain (a%e%,

identi&i(ation o& an* a%%o(iated >V.

Ci%H o& 'ro+re%%ion o& BD to ina%ie

"#i% ri%H o& 'ro+re%%ion #a% een (a($ated in a er* a''roxi)ate

and ne(e%%ari* ia%ed &a%#ion a%ed on %eera retro%'e(tie%t$die%. "#e ri%H a''ear% to e etGeen 3X and X &or ($taneo$%

BD, and aro$nd 10X &or Z$e*rat% er*t#ro'a%ia.R

>ro+re%%ion

o(($r% a&ter ar*in+ ti)e%, and (ini(a 're%entation inoe% t#e

a''earan(e on t#e &at 'a$e o& an o&ten $(erated t$)o$r. "#e

)eta%tati( ri%H %ee)% to e +reater t#an t#at o& t#e (o))on

&or).34,3

e* 'oint%

M A i% an e'ider)ad*%'a%ia.

M On%et o& A i% a%%o(iated Git# (#roni( ex'o%$re to V.

M "#e 'reaen(e o& A i% e%ti)ated at 112X in ad$t% oer

40 *ear% in t#e nort#ern #e)i%'#ere, and in(rea%e% Git# a+e.

M A i% (on%idered to e a 're(an(ero$% e%ion Git# a oG ri%H

o& 'ro+re%%ion to )ai+nan(* and a #i+# 'roaiit* o&

%'ontaneo$% re+re%%ion.

M "#e Q (on%ider% t#at A )eet% t#e (ini(a de&inition o& a

're($r%or o& , Git# G#i(# it %#are% a n$)er o& '#*%io-

'at#oo+i(a &a(tor%, $t a% t#ere i% no oi+ator* tran%ition

&ro) one to t#e ot#er, t#e di%tin(tion etGeen A and

%#o$d e )aintained.

M BD i% an intrae'ider)a in %it$ )o%t (o))on* %een

in t#e oGer i)%.

M "#e 'reaen(e o& BD i% $nHnoGn.

M "#e rate o& 'ro+re%%ion o& BD to ina%ie #a% not eena(($rate* deter)ined.

M A and BD )a* e iHened to oG-+rade and #i+#-+rade in-

trae'it#eia neo'a%ia% or % in %it$, re%'e(tie*, &o$nd

at ot#er %ite%. oGeer, t#eir (ini(a and aetioo+i(a &ea-

t$re% are %$&&i(ient* di%tin(t &ro) t#e%e e%ion% &or t#e) to

e (on%idered a% %e'arate.

M "o date, no %t$die% #ae de)on%trated t#e a$e o& treat-

)ent a%ed on t#e notion o& (an(eriKation &ied%.

II.3. Ina%ie ($taneo$% %$a)o$% (e (ar(ino)a%

"#e adje(tie% Tin&itratin+ and Tina%ie $%ed Git# are

%*n- on*)o$% and re&er to an* (ro%%in+ t#e a%a a*er o&

t#e e'i- t#ei$) and inadin+ t#e der)i%, re+arde%% o& t#e

de't# o& ina%ion.

II.3.1. De&inition, e'ide)ioo+* and nat$ra #i%tor* "#e a%t

)ajorit* o& (a%e% are &o$nd in %$n-ex'o%ed area%, %tartin+

&ro) an A, Git# G#i(# t#e* %#are n$)ero$% ri%H &a(tor%. "#e

'reaen(e o& in(rea%e% a% atit$de de(rea%e%. "#e ri%H

o& deeo'in+ i% a%o in&$en(ed * %Hin '#otot*'e, G#i(#

i% +eneti(a* deter)ined.

A n$)er o& (o-(ar(ino+en%, G#i(# )a* e &air* %ite-

%'e(i&i(, #ae een identi&ied, e.+. toa((o and o& t#e oGer

i'N +enita or ana >V and . @ore rare*, o(($r% in

BD, (#roni( $(eration, %(ar%, (#roni( ($taneo$% in&a))ation

e.+. #idradeniti% %$''$ritia radioder)atiti% or de noo.

$a)o$% (e (ar(ino)a i% a%o )ore (o))on in i))$-

node're%%ed 'atient% e.+. tran%'ant 'atient%, AID 'atient%,et(. and in t#e (o$r%e o& (ertain +enoder)ato%e%. "#e%e 'ar-

ti($ar %it$ation% are o$t%ide t#e %(o'e o& t#e 're%ent +$ide-

ine%.

"#e 'reaen(e and in(iden(e o& in


10/56

e* 'oint%

M "#e i)'ortan(e o& in ter)% o& '$i( #eat# i% do$t-

e%%* $ndere%ti)ated.

M In ieG o& t#e a+ein+ o& t#e V in&e(tion, %oG 'ro+re%%ion, e+etatie,

exo'#*ti( (ini- (a 're%entation and %oG in&itratin+ %'read.


11/56

"ae 2 ini(o-anato)i(a &or)% o& %$a)o$% (e (ar(ino)a: iterat$re ana*%i%

5o. '$i%#ed %erie%= ar+e%t no. (a%e% Qeedon @(ee Eder QO a%%arino @a+$ire ane

@etat*'i(a 2 49,0P 3 49P [; [; [; [; 0 0 0

Verr$(o$% 4 39,14P 46 4P [ [ [ [ [ [ [

A(ant#o*ti( L adenoidL'%e$doa%($ar 4 38,RP 1 6P[ [ [ [ [ [ [

i+)ented 1 61P [ 0 0 [ 0 [

De%)o'a%ti( 1 40P 44 [ [ 0 0 [ 0 [

@$(oe'ider)oid 1 39P 10 [ [ [ [ [ 0 0

ear (e== 0 5E [ [ 0 0 [ [ 0

i+net rin+ (e% 0 5E [ 0 0 [ 0 0

"ri(#ie))a 3 O6264P 13 O64P [ 0 0 [ 0 0

In&a))ator* 0 5E [ 0 0 0 0 0 0

*)'#oe'it#eio)a-iHe 4 O668P 40 O6RP [ 7 0 0 [ 0 0

Ba%aoid 1 20 O69P [ 0 0 0 0 0 0

ar(ino%ar(o)aL )eta'a%ti( 1 4 R0P [ [ 0 0 0 0 0

>a'iar* 1 3 R1P 0 0 0 0 [ 0 0

Ina%ie BoGen% di%ea%e 0 0 0 0 [ 0 0

=On* %t$die% Git# a )ini)$) o& t#ree (a%e% Gere (on%idered a% %erie%.

7"#i% &or) i% )entioned, $t i% not (on%idered* t#e a$t#or a% a /88 ariant.

@(ee +ro$'ed to+et#er (ear (e , %i+net rin+ /88 and tri(#ie))a /88 a% a %in+e entit*.

;In t#e%e re&eren(e%, )etat*'i(a (ar(ino)a Ga% a%%o(iated Git# B.

A%%o(iated )eano(*ti(-dendriti( (ontin+ent.

==etero+eneo$% &or) (o)'ri%in+ t$)o$r% Git# tri(#ie))a di&&erentiation and (a%e% in G#i(# (e$ar (ari&i(ation Ga% (a$%ed * de+eneratie '#e-

no)ena #*dro'i( a''earan(e o& (*to'a%) or a(($)$ation o& i'id a($oe%0.

5E, 5ot ea$ae.

i%too+i(a*, t#e%e a''ear a% a Ge-di&&erentiated

'roi&- eration o& (e% oer a on+ 'eriod, (o)inin+ a(ant#o%i%

and 'a'- io)ato%i%, Git# no (*too+i(a or ar(#ite(t$ra

ano)aie%. "#eir 'roi&eration %ee)% to '$%# a(H rat#er t#an

inade $nder*in+ ti%- %$e. At t#i% 'oint, t#e (ini(a 're%entation

and %ite )a* 'ro)'t a dia+no%i% o& .

"#i% %ta+e i% &ooGed * )arHed dee' in&itration, $t Git#

none o& t#e nor)a (riteria o& )ai+nan(*. "#e atter are %een

on* ater and in (ertain (a%e%, t#$% a((o$ntin+ &or o((a%iona*

exten- %ie o(a ina%ion at t#e ti)e o& dia+no%i%. "#e ri%H o&

)eta%ta%i% i% oG ee o& eiden(e 4.

"#e%e (a%e% are %i)iar to o(($rrin+ in err$(i&or)

e'ider- )a d*%'a%ia, a #ereditar* di%ea%e a%%o(iated Git# >V

in&e(tion. "#e ri%H o& %$(# e%ion% 'ro+re%%in+ to i% er*

#i+#, $t t#e e%ion% a++re%%iene%% doe% not a''ear to e +reater

t#an t#at o& (o))on .4R

@etat*'i(a or inter)ediate (ar(ino)a and )ixed

(ar(ino)a

"#e%e a)i+$o$% na)e% are $%ed &or rare t$)o$r%, de%(ried&or

t#e )o%t 'art in +$ideine% and re&eren(e ooH% $nder t#e

%e(tion on B. "#e* )a* e de%(ried %e'arate* or in

%o)e (a%e% to+et#er. One (o))on &eat$re i% t#eir a%%o(iation

Git# e'ider)a and a%aoid 'roi&eration, ot# o& G#i(# (arr*

)eta%tati( ri%H. In t#e Q% o'inion, t#i% j$%ti&ie% t#eir

a%%o(iation Git# .1

"#e

ter) )etat*'i(a or inter)ediate re&er% to a%aoid t$)o$r%,

$t t#e t$)o$r% do not 're%ent %tandard 'eri'#era 'ai%adin+

and are (o)'o%ed o& ar+er (e% t#at are (earer t#an t#o%e %eenin (o)- )on B.

1

@ixed (ar(ino)a a%o%$a)o$% (ar(ino)a, 'ro'o%ed in t#e

5@C +$ideine%R

a% a ariant o& , i% de&ined a% a &or) o&

B Git# %$a)o$% (ar(ino)ato$% di&&erentiation, (o)'ri%in+

t#ree (e t*'e%: a%aoid, %$a)o$% and inter)ediate, Git# ea(#

(o)'onent ein+ (ear* identi&iae.


12/56

Ge-(#ara(teriKed in t#e iterat$re in a n$)er o&

%i+ni&i(ant 'atient %erie%, and e(a$%e o& t#e i)'ortan(e o&

di%tin+$i%#in+ a++re%%ie %, radio-ind$(ed and

reatie* $ndi&&erentiated and non-di&&erentiated

to+et#er Git# t#e a%%o(iated 'roe)% o& #i%too+i(a

di&&erentia dia+no%i%, t#e Q de(ided to )aintain t#i% ariant

a% a di%tin(t &or) o& .

II.3.2.3. Variant% o& iHe* to #ae +reater )eta%tati( ri%H

Q#ie t#e%e &or)% )erit di&&erentiation in ter)% o& )or'#oo+*,

it i% di&&i($t to a%%e%% t#eir ee o& a++re%%iene%% a(($rate*,

+ien t#e %)a n$)er o& %t$die% aaiae and t#e retro%'e(tie

nat$re o& '$i%#ed %erie% ee o& eiden(e 4.

A(ant#o*ti( e'ider)oid (ar(ino)a

"#i% &or) a((o$nt% &or 24X o& ,'arti($ar* o& t#e #ead and

ne(H, G#ere it +enera* a''ear% &ooGin+ a(ant#o*ti( A.39,68

A% a re%$t o& &o(a or exten%ie a(ant#o*%i%, t$)o$ra

o$e% (reate '%e$do+and$ar adenoid %tr$(t$re%. "#e%e

(aitie% )a* (ontain a)or'#o$%, a%o'#ie )atter o& %e(retor*a''earan(e, $t do not (ontain an* )$(ino$% %e(retion

identi&iae $%in+ t#e $%$a %tainin+ )et#od% 'eriodi( a(id-

(#i&&, a(ian $e, )$(i(ar)ine, et(.. "#e $)en% o& t#e%e

(aitie% (ontain at*'i(a and o((a%ion- a* )$tin$(eate

d*%Heratoti( (e%.

In %o)e (a%e%, t#e &or)ation o& intrat$)ora (aitie% i% %$(#

t#at t#e t$)o$r )a* %$++e%t an+io%ar(o)a at t#e #i%too+i(a

ee. Dia+no%i% o& t#i% '%e$doa%($ar &or) )a* re$ire

i))$no- #i%to(#e)i(a ana*%i%.

"#e tGo )ain %erie%'$i%#ed ee o& eiden(e 4 *ieded (on-

tradi(tor* re%$t% re+ardin+ 'ro+no%i%.R,8

In t#e ode%t %erie%

(o)- 'ri%in+ 1 'atient%, t#ere Gere &ie (a%e% o& deat#a%%o(iated Git# di%tant )eta%ta%e% or o(a ina%ion. In t#e

)o%t re(ent %erie% inoin+ (a%e% in 49 'atient%, )eta%ta%e%

Gere o%ered in 19X o& (a%e% and &ooGed * deat#, t#e atter

o$t(o)e (orreatin+ Git# a t$)o$r %iKe in ex(e%% o& 1. ().

Adeno%$a)o$% (ar(ino)a40,R6

"#i% e%ion i% (#ara(teriKed * t#e (o-exi%ten(e o& -t*'e

'roi&- eration ex're%%in+ Heratin R and )$(o%e(retor* t$$ar

%tr$(t$re% Git# a (ontent 'o%itie &or )$(i(ar)ine and a(ian

$e. "#e t$$ar %tr$(t$re% are ordered * at*'i(a ($oida

(e% ex're%%- in+ (ar(inoe)r*oni( anti+en.

Di&&erentia dia+no%i% )$%t e )ade Git# a '%e$do+and$ar

a(ant#o*ti( and )eta%ta%e%, 'arti($ar* )$(oe'ider)oid

(ar(ino)a o& t#e %aiar* +and%.

In a reieG o& 13 (a%e%, t$)o$r dia)eter Ga% etGeen 0.

and

() )ean: 2.2 () Git# )arHed a++re%%iene%% and a #i+#

rate o& rea'%e 6 L13 and deat# ee o& eiden(e 4 a&ter a

&ooG- $' ran+in+ &ro) 2 )ont#% to 6 *ear% )ean: 32 )ont#%.

on%e- $ent*, t#e Q de(ided to (a%%i&* t#i% entit* a% a

%e'arate ariant o& .

De%)o'a%ti( e'ider)oid (ar(ino)a

"#i% &or) i% de&ined #i%too+i(a* * t#e &ooGin+ (riteria:

t$)o$r (e% (o)'ri%in+ %$a)o$% di&&erentiation and &or)in+

)ore or e%% ran(#ed (#ain% Git#in an a$ndant Tde%)o'a%ti(

&iro$% %tro)a, G#i(# * de&inition o(($'ie% at ea%t 30X o& t#e

entire t$)o$r. "#e 'ro%'e(tie %t$d* * Bre$nin+er et a.41

inoin+ 94 (a%e%, Git# a &ooG-$' ran+in+ &ro) 4 to

10 *ear% )edian: .3 *ear%, (o)'ri%ed 44 (a%e% )eetin+

t#e%e (riteria. 5o di&&eren(e% Gere o%ered etGeen

de%)o'a%ti( and (o))on re+ardin+ +ender, a+e or

di%tri$tion in %$n- ex'o%ed area%, $t t#e n$)er o& (a%e% o&

)eta%tati( 'ro+re%%ion Ga% %ix ti)e% #i+#er and Ga% de'endent

on t$)o$r t#i(Hne%% ee o& eiden(e 4. "#i% %t$d* ed t#e Q

to (on%ider t#e entit* a% a ariant o& .

II.3.3. I))$no#i%to(#e)i(a )arHer% At#o$+# t#ere are a%

*et no 'ro+no%ti( )arHer% or )oe($ar )arHer% tran%o(ation or

re($rrent +eneti( ano)a* %'e(i&i( &or and 're($r%or

e%ion%, i))$no#i%to(#e)i(a )arHer% o& di&&erentiation (an e

$%ed to re%oe %eera 'roe)% re+ardin+ di&&erentia dia+no%i%

"ae 3.

"#e $%e o& i))$no#i%to(#e)i(a )arHer% i% at t#e di%(retion

o& t#e 'at#oo+i%t, a%ed on t#e a''earan(e o& t#e indiid$ae%ion. 5o indiid$a )arHer% )a* e re(o))ended &or ro$tine

'ra(ti(e. I))$no#i%to(#e)i%tr* (an aid t#e di&&erentia dia+no%i%

etGeen &$%i&or) , at*'i(a &iroxant#o)a, ($taneo$% %ar-

(o)a or &$%i&or) )eano)a * de)on%tratin+ t#e ex're%%ion*

t$)o$r (e% o& e'it#eia )arHer%: (*toHeratin% , nota*

#i+# )oe($ar Gei+#t (*toHeratin% -6, 34aE12 and

@5


13/56

"ae 3 Di&&erentia dia+no%i% etGeen and 're($r%or

e%ion%: i))$no#i%to(#e)i(a )arHer%"#ere are no ioo+i(a )arHer% aoGin+ &or t#e tGo &or)% to

e di%tin+$i%#ed. ertain anti+en% a''ear to e ex're%%ed

di&&erent*

Di&&erentia

dia+no%i%

eratoa(ant#o)a Qe-di&&erentiated

%e&$ #i%to(#e)i(a)arHer%=

5one

in Heratoa(ant#o)a% and , %$''ortin+ t#e notion t#at

Hera- toa(ant#o)a %#o$d e (on%idered a% a %e'arate entit*.R981

5one o& t#e%e )arHer%, #oGeer, i% %$&&i(ient* %en%itie or%'e(i&i( to

A(tini( Herato%i% D$re$i# )eano)a @eano(*ti( )arHer%

eorr#ei( Herato%i% 5one

BoGen% di%ea%e In %it$ )eano)a *toHeratin[

@eano(*ti( )arHer%

>a+et% di%ea%e *toHeratin 20\N(*toHeratin R0

er o& t$)o$r%, initia* eieed to e Heratoa(ant#o)a%, %$%e-

$ent* 'ro+re%%ed in t#e %a)e Ga* a% , in %'ite o& #ain+ a

%ee)in+* (#ara(teri%ti( (ini(o-anato)i(a a''earan(e.29,82

Q#ie t#e%e &a(t% re)ain too rare to r$e o$t t#e exi%ten(e o&

Heratoa(ant#o)a and it% &ao$rae 'ro+no%i%, a n$)er o& ar+$-

>oor*

di&&erentiated

&$%i&or)

At*'i(a

&iroxant#o)a

E'it#eia )arHer%[

-6, 34E12,

@5116, and '63

)ent% )$%t e taHen into a((o$nt &or t#era'e$ti( )ana+e)ent:

M %'ontaneo$% re+re%%ion )a* taHe )ore t#an 4 )ont#%N

M exten%ie $(ero$% 'ro+re%%ion i% 'o%%ie, 'arti($ar* on$taneo$% %ar(o)a E'it#eia )arHer%[

-6, 34E12,

@5116, and '63

100, @eanA

t#e no%e and e*eid%N

M %(ar% t#at re)ain &ooGin+ %'ontaneo$% re+re%%ion are&re$ent* $n%i+#t*N

M #i%too+i(a di%tin(tion etGeen Heratoa(ant#o)a and t#e

(rateri&or) ar(#ite(t$re o& )a* e di&&i($t or een

i)'o%%ie,81

a% &ar a% io'%ie% or 'artia re%e(tion% are

(on(erned.

Verr$(o$% E'ider)a 5one "#e Q t#$% re(o))end% t#at 'at#oo+i%t% %#o$d on* )aHe #*'er'a%ia a dia+no%i% o& Heratoa(ant#o)a G#en t#e* are ae to a%%e%% t#eA(ant#o*ti(

An+io%ar(o)a E'it#eia )arHer% [

Va%($ar )arHer%0ar(#ite(t$re o& t#e entire e%ion in t#e io'%* %a)'e. "#e Q

(on%ider% t#at, in at*'i(a (a%e%, ex(i%ion o& t#e (ar(ino)a i% Gar-

Adenoid-

e'ider)oid

Adeno(ar(ino)a

I or II

Adeno(ar(ino)aI adnexa or II

>ro&ie o& (*toHeratin

ex're%%ion

5one

ranted. In t*'i(a (a%e%, %$r+i(a ex(i%ion i% 're&erae to t#e

%tandard TGait and %ee a''roa(# %ee %e(tion V.6.

@ixed B 5one e* 'oint%De%)o'a%ti( (eroder)i&or) 5one eratoa(ant#o)a %#o$d e (on%idered a% a %e'arate entit* &ro) B

="#e re%$t% %#oGn are t#o%e nor)a* &o$nd in /88 and 're($r%or

e%ion%.

I S 'ri)ar* t$)o$r, II S %e(ondar* t$)o$r.

II.4. eratoa(ant#o)a

Dia+no%i% o& Heratoa(ant#o)a i% (a%%i(a* a%ed on t#e

a%%o(iation o& (ini(a and #i%to'at#oo+i(a (riteria:

M t$)o$r o& ra'id on%et, (entred aro$nd a Heratoti( (raterN

M %*))etri(a +enera or+aniKation o& t#e e%ion aro$nd t#e(entra (rater o(($'ied * HeratinN

M t$)o$r T#ooHed to %$rro$ndin+ e'ider)i% on eit#er %ide

o& t#e (raterN

M ar+e Heratino(*te% Git# (ear (*to'a%)N

M oG )itoti( indexN

M %'ontaneo$% re+re%%ion Git#in 24 )ont#%.

"#e nat$re o& Heratoa(ant#o)a and it% reation%#i' Git#

#ae een deated * n$)ero$% a$t#or%, in($din+ 5@C

ex'ert%, G#o (on%ider Heratoa(ant#o)a to e a +enera*

re+re%%ie &or) o& .6,R

"#e tGo t$)o$r &or)% %#are a n$)er

o& e'ide- )ioo+i(a &a(tor%, in addition to a+e at on%et and

to'o+ra'#*.

.

"#e (ini(a and #i%too+i(a &eat$re% o& Heratoa(ant#o)a, a%

Ge a% it% 'ro+re%%ion, aoG it to e di%tin+$i%#ed &ro) ,

'roided t#e ar(#ite(t$re o& t#e entire e%ion (an e ea$ated

on t#e io'%* %a)'e. >artia io'%* doe% not nor)a* enae

&or)a di&- &erentiation etGeen Heratoa(ant#o)a and .

III. >ro+no%ti( &a(tor% &or

>ro+no%i% i% +ood &or t#e )ajorit* o& . "#e )eta%tati( ri%H

ro$+#* e%ti)ated in t#e iterat$re $%in+ t#e ratio o& n$)er o&

)eta%ta%e%L n$)er o& (a%e% de%(ried i% 2.3X at *ear%

and

.2X a&ter &ooG-$' o& oer *ear% &or on %$n-ex'o%ed %Hin.

"#e &re$en(* o& rea'%e or )eta%ta%i% and o& )ortait* a%%o(i-

ated Git# i% +enera* d$e to ate or ina''ro'riate initia

treat)ent o& t#e t$)o$r or to t#e exi%ten(e o& a++re%%ie (ini(o-

anato)i(a &or)%.

Q#ie t#e ada'ted +$ideine% 'roide a n$)er o& &air*

(o#erent ee)ent% (on(ernin+ 'ro+no%ti( &a(tor% &or , t#e

eiden(e i% rare* o& ee 2 and +enera* o& ee 4. "#e

ario$% 'ro+no%ti( &a(tor% #ae een ine%ti+ated )ain* in

retro%'e(tie %t$die%, G#i(# di&&ered in ter)% o& ot# ana*ti(a)et#od% and


14/56

(riteria $%ed, and o& 'ra(ti(e and re(r$it)ent o& tea)%. "#e t#ree

ada'ted 'ra(ti(e +$ideine%83

'roide detai% o& t#e ar+e

reieG * CoGe,83

G#i(# (oer% a %ee(tion o& retro%'e(tie

%t$die%'$-

"ae 4 >ro+no%ti( &a(tor% &or a((ordin+ to 55

oG ri%H i+# ri%H

i%#ed etGeen 1940 and 1992, a% Ge a% %eera )ore re(ent

retro%'e(tie %erie%, t#ree (o#ort %t$die%, a 'ro%'e(tie %t$d*

ea$atin+ t#e de&inition o& at-ri%H 'atient%848R

and anot#er

%t$d* de%i+ned to a%%e%% t#e #i%to'ro+no%ti( a$e o& t$)o$r

t#i(Hne%%.88

"#e 5@C +$ideine%83 i%t %een ri%H &a(tor%:

ini(a

ite L %iKe ]one B ^20 )) ]one B 20 ))

]one I ^10 )) ]one I 10 ))]one ^6 )) ]one 6 ))

Ed+e% Qe de&ined >oor* de&ined

>ri)ar* %. re($rren(e >ri)ar* (ar(ino)a Ce($rren(e

I))$node're%%ion 5o e%

1 "5@ (a%%i&i(ation %ta+e. "#i% i% $%ed in t#e a%en(e o& an* on radioe%ion or 5o e%

etter (a%%i&i(ation, at#o$+# 'oor %$itaiit* &or #a%

een 'ointed o$t. Qit# re+ard to ", 'riorit* i% +ien to

in&a))ator* e%ion

Ca'id-+roGi n+ 5o e%

externa dia)eter to de&ine %ta+e% "1 to "3, irre%'e(tie o&

t#e de+ree o& der)a and #*'oder)a ina%ion, G#erea% "4

i% de&ined a% ina%ion o& dee' )$%(e and one a*er%.

2 >re%en(e o& o(a *)'#ati( )eta%ta%e% or 'erine$ra 'ro'a-

5e$roo+i(a

%*)'to)%

i%too+i(a

De+ree o&

di&&erentiation

5o e%

Qe di&&erentiated @oderate* or

'oor*

+ation. di&&erentiated

3 o(a re($rren(e or in(o)'ete treat)ent, +ro$'ed to+et#er

a% t#e* are interde'endent.

4 i%too+i(a +rade Ge di&&erentiated, &air* Ge di&&erenti-

erine$ra or a%($ar

ina%ion

I, II, III or ^4 )) IV, V or 4 ))

5o e%

are t#o%e &o$nd on t#e %(a', ear and er)iion order o&

t#e i'N

6 5on-'#oto-ind$(ed in i))$no(o)'etent 'atient%

on (#roni( o%teo)*eiti% &i%t$a%, $rn %(ar% or radio-

t#era'* area%N

R in i))$node're%%ed %$je(t% not deat Git# in t#e%e+$ideine%.

M "#e BAD +$ideine%83

&$rt#er add tGo (riteria &or 'oor

'ro+no%i%: )i(ro%(o'i( )ea%$re)ent o& t$)o$r t#i(Hne%%

+reater t#an 4 )) and ee V #*'oder)i( ina%ion, Git#

re&eren(e to arH% )eano)a (a%%i&i(ation.

M "#e 55 +$ideine%83

di%tin+$i%# t#e (ini(a and 'at#-

oo+i(a ri%H% i%ted in t#e &ooGin+ tae.

In reait*, G#ie t#e )ajorit* o& (riteria i%ted in t#i% tae

re&er to , t#e de&inition o& ri%H a%%o(iated Git# %ite in t#ree

area%: , I and B (annot e a((e'ted, a% t#e 55

ex'ert% #ae de&ined t#e%e ri%H &a(tor% a%ed on rea'%e rate%

in a %erie% o& B. "#e &o$r arti(e% '$i%#ed * t#e %a)e

tea) ier)an et a. Gere a%ed on a retro%'e(tie %t$d*

inoin+ ,R B (a%e%, 2,314 o& G#i(# Gere treated *

($retta+e and (a$ter*, 862 * radiot#era'* and on* 88 *

%$r+er*. ite Ga% a ri%H &a(tor inde'endent o& rea'%e, on* in t#e

B +ro$' treated * ($retta+e and (a$ter*. In t#e %$r+er*

+ro$', t#e on* ri%H &a(tor% inde- 'endent o& re($rren(e Gere

o(ation in t#e (e'#ai( extre)it* in t#e a%en(e o& an* &$rt#er

in&or)ation and )ae +ender. on%e- $ent*, t#e Q de(ided

not to &ooG t#e 55 'ro'o%a o& di%tin+$i%#in+ t#ree

($taneo$% area% Git# di&&erent ri%H ee% &or "ae 4.

oG-ri%H area B0: tr$nH and i)%.

Inter)ediate-ri%H area I0: (#eeH%, &ore#ead, %(a', and ne(H.

i+#-ri%H area 0: (entra &a(ia re+ion e*eid%, e*eroG%, 'eriorita

re+ion, no%e, i'%, (#in and jaG, ear and 'eria$ri($ar re+ion, te)'e%,

+enita re+ion% a% Ge a% #and% and &eet.

III.1. ini(a 'ro+no%ti( &a(tor% in 'ri)ar*

III.1.1. "$)o$r %ite "#e ri%H o& o(a re($rren(e and )eta%ta%i%

arie% a((ordin+ to t#e initia t$)o$r %ite, $t t#i% ri%H i%

di&&i($t to ea$ate a% t#e (ond$(ted %t$die% eit#er inoe %)a

n$)er% o& (a%e% or do not re'ort (orreation% Git# t$)o$r

t#i(Hne%% and de't# o& ina%ion.R,9,83

e%ion% o(($rrin+ in %$n-ex'o%ed area% ot#er t#an t#e i'% and

ear% (arr* t#e oGe%t ri%H o& re($rren(e.

ite% re'orted a% (arr*in+ t#e #i+#e%t ri%H o& rea'%e or

)eta%ta- %i% are:

0 'eriori&i(ia area% no%e, i'%, o$ter ear and e*eid% and

%(a'N

0 (ar(ino)a% ori+inatin+ in non-%$n-ex'o%ed area% 'eri-

ne$), %a(r$) and %oe% o& t#e &eet or on radioder)ati-

ti%, $rn %(ar%, (#roni( in&a))ation or (#roni( $(er%

ee o& eiden(e 4.

III.1.2. e%ion dia)eter At#o$+# t#i% 'ara)eter )a* e (on%id-

ered to e an i)'re(i%e re&e(tion o& a(t$a t$)o$r o$)e, it i%

're%ented a% a 'ro+no%ti( &a(tor in t#e 5@C, 2002 BAD

and 55 +$ideine%. It i% t#e %oe (riterion e)'o*ed in t#e

"5@


15/56

%Hin (an(er (a%%i&i(ation, G#i(# $%e% tGo t#re%#od% to

(a%%i&* t$)o$r dia)eter: 2 and () "1 to "3. "#i%

(a%%i&i(ation )aHe% no re&eren(e to de't# o& ina%ion ot#er

t#an &or t#e )o%t adan(ed t$)o$r% "4: in&itration o&

)$%(e, one or (artia+e.

In t#e reieG * CoGe,83

t$)o$r% Git# a dia)eter o& 2 () or

)ore are (on%idered to (arr* a tGo&od ri%H o& o(a rea'%e and a

t#ree&od ri%H o& di%tant )eta%ta%e% at *ear% in (o)'ari%on

to t$)o$r% Git# a dia)eter o& e%% t#an 2 (). "#e -*ear rea'%e

and )eta%ta%i% rate% &or t#e atter are neert#ee%% R.4X and

9.1X, re%'e(tie*, G#i(# i% &ar &ro) ne+i+ie. eera )ore

re(ent retro%'e(tie %t$die% and one 'ro%'e(tie %t$d* %#oG

%i)iar &ind- in+%8493

e9e o& e9iden(e 2.

A t$)o$r %iKe o& 2 () )a* t#$% e (on%idered a% a

%i+ni&i(ant 'ro+no%ti( &a(tor, $t t#e a&ore)entioned rea'%e

&i+$re% %$++e%t t#at in ter)% o& t$)o$r %iKe, t#e %a&et* t#re%#od

i% in &a(t oGer, 'arti($ar* at-ri%H %ite% ee o& eiden(e 4.

A% Ge %#a %ee at at-ri%H %ite%, ot#er %t$die% %$++e%t t#at

e%ion dia)eter i% 'roa* not t#e )o%t reeant 'redi(tie&a(tor, and t#at ot#er &a(tor% )$%t e taHen into a((o$nt.

III.1.3. o(a re($rren(e o(a re($rren(e i% a %i+ni&i(ant ri%H

&a(tor &or *)'# node or di%tant )eta%ta%e%. It i% t#e re%$t

o& eit#er non-(o)'ian(e Git# t#e r$e% (on(ernin+ ex(i%ion

)ar+in% or #i%too+i(a eri&i(ation o& t#e%e )ar+in% or, )ore

rare*, o(a *)'#otro'i( )i(ro)eta%ta%e%. In a 'ro%'e(tie

%t$d* inoin+

193 'atient% Git# #ead and ne(H , a %i+ni&i(ant (orreation

Ga% o%ered etGeen *)'# node )eta%ta%e% and rea'%e.8

Ot#er %t$die% indi(ate #i+# rate% o& )eta%ta%i% &ooGin+ rea'%e,

ran+in+ &ro) 2X to 4X a((ordin+ to t#e re+ion.83,89,92

"#eri%H o& o(a re($rren(e, #oGeer, i% not inde'endent o& t$)o$r

%iKe or initia t$)o$r %'read, a% t#e atter &a(tor% deter)ine

t#e di&&i($t* o& ex(i%ion in %ano, and t#$% o& %ati%&a(tor* o(a

(ontro ee o& eiden(e 4.

III.1.4. I))$node're%%ion In(rea%ed in(iden(e o& &ooG-

in+ or+an tran%'antation #a% een Gide* de)on%trated,94

at#o$+# o'inion% on t#i% %$je(t di&&er. In a (o#ort %t$d*

inoin+ ,36 tran%'ant 'atient%, t#e ri%H o& %Hin (an(er

non-)eano)a and non-B Ga% 100 ti)e% +reater t#an in

t#e +enera 'o'$ation94

ee o& eiden(e 2.

In addition, t#e ri%H o& a tran%'ant 'atient deeo'in+

i% a%%o(iated Git# t#e de+ree o& on+-ter) iatro+eni(

i))$no- %$''re%%ion. A&ter a+e adj$%t)ent, rena tran%'ant

'atient% re(eiin+ (*(o%'orine, aKat#io'rine and 'redni%oone

are at %i+- ni&i(ant* #i+#er _2.8 ri%H t#an t#o%e re(eiin+

d$a t#era'* Git# aKat#io'rine and 'redni%oone. erine$ra ina%ion ne$rotro'i%) >erine$ra ina%ion

>5I o& o(($r% o((a%iona*, Git# an e%ti)ated 'reaen(eo&

2.14X. Q#en a%%o(iated Git# &a(ia t$)o$r%, it re%$t% in a

ri%H o& %*)'to)ati( intra(rania (ar(ino)ato$% ne$ro'at#*,

G#i(# i% +enera* o%ered at t#e tri+e)ina nere V and

&a(ia nere VII, a% Ge a% at ot#er %ite%, Git# #i+# ee% o&

rea'%e and


16/56

)eta%ta%i%. In a %t$d* inoin+ 96R (a%e% in 20 'atient%,

>5I Ga% dete(ted in 14X o& 'atient%. In t#e atter +ro$', an

in(rea%e in rate% o& ot# *)'# node )eta%ta%i% 3X %. 1XN

> ^ 0.000 and di%tant )eta%ta%i% 1X %. 3XN > ^ 0.000

Ga% o%ered in (o)'ari%on Git# 'atient% Git#o$t >5I.99

A

re(ent A$%traian %t$d* in($ded 1,1RR 'atient% $nder+oin+ @o#%

%$r+er* &or , 336 o& G#o) Gere &ooGed oer a -*ear

'eriod. >5I Ga% re'orted in R0 (a%e% .9X, 2 o& G#i(#

Gere &ooGed oer *ear%, t#e 'er(enta+e rea'%e rate in t#e

>5I +ro$' ein+

8X %. 3.RX in t#e +ro$' Git#o$t >5I > S 0.0298

ee o&ei-

den(e 2.

III.2.3. De+ree o& (*too+i(a di&&erentiation a%%i&i(ation o&

a((ordin+ to t#e de+ree o& di&&erentiation Ga% taHen a% a

'ro+no%ti( &a(tor in t#e t#ree ada'ted +$ide%. "#e &o$r roade%t

(a%%i&i(ation +rade%, a%ed on t#e ratio o& di&&erentiated to

$ndi&- &erentiated (e% +rade 1 S 3:1, +rade 2 S 1L1, +rade 3 S1L 3 and +rade 4 S no tenden(* toGard% di&&erentiation are

rare* $%ed in 'ra(ti(e. "#e )ajorit* o& 'at#oo+i%t% neert#ee%%

$%e a %i)'i&ied (a%%i&i(ation inoin+ de%(ri'tion o& t$)o$r

di&&erentiation a%

TGe di&&erentiatedJ, T%i+#t* di&&erentiatedJ orT$ndi&&erentiatedJ.

In t#e reieG * CoGe, in t#e eent o& ot# reatie*

$ndi&&erentiated or $ndi&&erentiated t$)o$r%, (arrie% a

tGo&od ri%H o& o(a rea'%e and a t#ree&od ri%H o& )eta%ta%i% in

(o)'ari%on to Ge-di&&erentiated t$)o$r%83,88,89

ee o& eiden(e

4.

III.2.4. i%too+i(a t*'e Di%tin(tion etGeen (ertain#i%too+i(a &or)% o& Ga% )ade on* in t#e 55

+$ideine%, G#i(# di&- &erentiate etGeen )ixed, a(ant#o*ti(,

)$(oe'ider)oid and de%- )o'a%ti( &or)%.8

"#e %t$d* o& #i%to'ro+no%ti( (a%%i&i(ation *

a%%arino et a.46,4R

Ga% a%ed $'on a ar+e iterat$re reieG.

It $%ed t#e 'er(enta+e o& )eta%ta%i% (a%e% in reation to t#e

n$)er o& '$- i%#ed (a%e%, Git#o$t %'e(i&*in+ t#e d$ration

o& o%eration. A((ordin+ to t#i% )et#od o& (a($ation, t#e

+ro$' o& oG-ri%H

"ae ini(a "5@ (a%%i&i(ation o& non-)eano)a %Hin

(an(er%

>ri)ar* t$)o$r "

"W: 'ri)ar* t$)o$r (annote ea$ated

"0: no identi&iae 'ri)ar* t$)o$r

"i%: (ar(ino)a in %it$

"1: t$)o$r 2 () a(ro%% ar+e%t dia)eter

"2: t$)o $r2 () " () a(ro%% ar+e%tdia)eter

"3: t$)o$r ` () a(ro%% ar+e%t dia)eter

"4: t$)o$r inadin+ dee' %tr$(t$re%: (artia+e,one or %triated )$%(e

5B: )$ti'e %i)$taneo$% t$)o$r% are (a%%i&ied $nder t#e

#i+#e%t " Git# t#e n$)er o& t$)o$r% indi(ated inra(Het%

Ce+iona *)'# node% 5

5W: re+iona *)'# node% (annote ea$ated

50: no re+iona *)'# node )eta%ta%i%

51: re+iona *)'# node )eta%ta%i%

a )i(ro)eta%ta%i%

%in+e )a(ro)eta%ta%i% in t#e #o)oatera area,

dia)eter ^3 ()52:

a %in+e )eta%ta%i% in t#e #o)oatera area,

dia)eter `3 () ^6 ()

)$ti'e )eta%ta%e% in t#e #o)oatera area, dia)eter 6 ()

( re+iona intra*)'#ati( )eta%ta%e% in-tran%it or %ateite

53:

a iatera or (ontraatera )eta%ta%e%

*)'# node )eta%ta%e% Git# ina%ion o& t#e &a(ia re+ion or a%e o& %H$

Di%tant )eta%ta%e% @

@W: di%tant )eta%ta%e% (annote ea$ated

@0: no di%tant )eta%ta%e%

@1:di%tant )eta%ta%e%

ta+in+

ta+e 0 "i% 50 @0

ta+e I "1 50 @0

ta+e II "2 50 @0

"3 50 @0

)eta%tati( ri%H 2X in($ded t#e (o))on &or),ta+e III "4 50 @0

err$(o$% (ar(ino)a%, &$%i&or) ex(e't &or &$%i&or)

in irradiated area%, a% Ge a% )ixed and )etat*'i(a (ar(ino-ta+e IV

a "

a "

51

a5

@0

@1)a%. "#e inter)ediate-ri%H +ro$' 310X ri%H o&)eta%ta%i%

(on%i%ted o& t#e a(ant#o*ti( &or), G#erea% t#e #i+#-ri%H +ro$'

)eta%tati( ri%H `10X (o)'ri%ed t#e ina%ie &or) o&

BoGenJ% di%ea%e and de%)o'a%ti( and )$(oe'ider)oid

ee o& eiden(e 4.

III.3. >ro+no%ti( (a%%i&i(ation o& 'ri)ar*

"o date, no %ati%&a(tor* 'ro+no%ti( (a%%i&i(ation exi%t% &or

'ri)ar* . "#e "5@ (a%%i&i(ation deeo'ed * AJ L

IA L I "ae and a''ied to a &or)% o& non-

)eano)a %Hin (an(er, i% not %$itae &or . It $%e% t$)o$r

%iKe at it% +reate%t dia)eter a% t#e %oe (riterion &or "1 to "3,

Git# t#re%#od% at 2 and (), and de&ine% %ta+e "4 in ter)% o&

ina%ion o& dee' %$der)a %tr$(- t$re%: (artia+e, %triated )$%(e

orone.


17/56

i%to'at#oo+i(a (a%%i&i(ation '"5@.

"#e (ate+orie%'", '5 and '@ (orre%'ond to (ate+orie% ", 5 and @.

'50: i%too+i(a exa)ination o& *)'# node ($retta+e %a)'e% )$%t

in($de %ix or )ore *)'# node%.

Q#ie t#e%e %#ort(o)in+% Gere re+retted * t#e a$t#or% o& t#e

ada'ted +$ideine%, no aternatie% Gere %$++e%ted. A )ore 're-

(i%e 'ro+no%ti( (a%%i&i(ation Go$d 'er)it etter ea$ation o&

ri%H ee, identi&i(ation o& 'atient +ro$'% Git# (o)'arae ri%H

and i)'roed %ee(tion o& t#era'e$ti( o'tion%. $(# a (a%%i&i(a-

tion Go$d re$ire re%$t% &ro) a 'ro%'e(tie %t$d* inoin+ a

ar+e 'atient (o#ort, Git# )$tiariate ana*%i% o& )$ti'e 'oten-

tia &a(tor%.


18/56

"#e Q &et t#at e(a$%e retro%'e(tie %t$die% o& 'atient%erie%

"ae 6 >ro+no%ti( (a%%i&i(ation o&

'roided no indi(ation a% to G#et#er )or'#oo+i(a ariant% Gerero$ 2: %i ni&i(ant

a di%(ri)inatin+ 'ro+no%ti( 'ara)eter, inde'endent* o& t$)o$r riteria ro$' 1: oG ri%H ri%H

t#i(Hne%% and de't# o& ina%ion in 'arti($ar, it Go$d e di&&i($t ini(a

to ado't t#i% (a%%i&i(ation a% it %tand%. >ri)ar* %. >ri)ar* Ce($rren(e

"#e e%t e%tai%#ed ariant% )a* neert#ee%% e (a%%i&ied into re($rren(e

tGo +ro$'%:

M &o$r ariant% o& Git# oG )eta%tati( ri%H: (o))on,

err$(o$%, &$%i&or) ex(e't &or t#o%e inoin+ irradiated

De+ree o& (ini(a

in&itration

5e$roo+i(a

%*)'to)% o&

A%en(e Ad#e%ion to dee'

%tr$(t$re%

5o e%

area% a% Ge a% )ixed and )etat*'i(a N

M t#ree &or)% t#at are iHe* to e )ore a++re%%ie: a(ant#o-

ina%ion

I))$ne %tat$% I))$no(o)'ete nt I))$node're%%ed

*ti( , de%)o'a%ti( and )$(oe'ider)oid .

Ce(o))endation%

iKe dia)eter

de'endin+ on

%ite

i%to'at#oo+i(a

^10 )) in area C[7

^20 )) in area C0=

10 )) in area C[=

20 )) in area C07

"#e Q %$++e%t% $%in+ a 'ro+no%ti( (a%%i&i(ation t#at di%tin- >erine$ra ina%ion 5o e%+$i%#e% etGeen tGo +ro$'% on t#e a%i% o& %ix (ini(aand

De+ree o& (e$ar ood @oderate to

&ie #i%too+i(a (riteria 'ro&e%%iona(on%en%$%.

di&&erentiation $ndi&&erentiated

"Go o& t#e%e (riteria, (ini(a %iKe and %ite, are reated: t$)o$r

%iKe t#re%#od i% de'endent on %ite "ae 6.

ro$' 1: Git# oG ri%H o& re($rren(e andLor )eta%ta%i%

i%too+i(a &or)% o))on, err$(o$%,

&$%i&or) o$t%ideirradiated area%,

)ixed or

De%)o'a%ti( `

)$(oe'ider)oid `

a(ant#o*ti(

"#i% (o)'ri%e% on* Git# +ood 'ro+no%ti( (riteria. "reat- )etat*'i(a

)ent &or t#e%e i% ea%* to (odi&* and )a* e de(ided

$'on Git#o$t needin+ a )$tidi%(i'inar* (on%$tation ID.

ro$' 2: ot#er Git# %i+ni&i(ant ri%H o& re($rren(e andLor

"$)o$r de't#

arH ee

"#i(Hne%%

ee IIIt#i(Hne%% 3 ))

ee IV

t#i(Hne%% `3 ))

)eta%ta%i%

A %in+e (riterion in t#e Tat %i+ni&i(ant ri%H (o$)n i%

%$&&i(ient &or to e in($ded in t#i% +ro$', $t it )$%t e

%tre%%ed t#at t#i% +ro$' i% #i+#* #etero+eneo$% in ter)% o&'ro+no%i% &or t#e &ooGin+ rea%on%:

M


19/56

(#a'ter to )eta%ta%e%. *)'# node area %tat$% #a% a

%tron+earin+ on 'ro+no%i%, a% t#e 'roaiit* o& -*ear %$ria

&or *)'# node )eta%ta%i% i% o& t#e order o& 40X, G#erea% rea'%e

at a *)'# node %ite &ooGin+ radi(a *)'#ati( ($retta+e i% &ata

in )o%t (a%e%. "#e A$%traian a$t#or% %tre%% t#e oer-%i)'i&ied

nat$re o& t#e "5@ (a%%i&i(ation o& %Hin (an(er%, G#i(#

di%tin+$i%#e% on*etGeen 50 and 51, Git#o$t taHin+ into

(on%ideration t#e tGo %i+ni&i(ant #i%to'at#oo+i(a &a(tor%

'redi(tie &or ri%H o& re+iona re($rren(e &ooGin+ radi(a

*)'#adene(to)*, na)e* t#e n$)-er o& )eta%tati( *)'#

node% and 'erinoda ina%ion (a'%$e

r$'t$re.R

"#e%e (riteria )a* e ea$ated to %o)e extent $%in+ i)a+in+

)et#od% d$rin+ t#e 'reo'eratie GorH-$', $t t#e* are

eent$a* a%ed $'on #i%to'at#oo+i(a exa)ination o& t#e

%$r+i(a ($retta+e ti%%$e %a)'e.

noGed+e o& t#e%e &a(tor% (an e $%ed to )ore

a(($rate* deter)ine t#e 'ro+no%i% o& *)'# node inoe)ent.

5$)er o& 5 inaded $ria

at *ear%

1 49X

2 30X

3 or )ore 13X

Extra(a'%$ar exten%ion

A%ent 4RX

>re%ent 23X

"#e 2002 BAD +$ideine%, dedi(ated to 'ri)ar* t$)o$r%, do

not dea Git# t#i% to'i(.

"#e 55 +$ideine% a((e't t#e "5@ (a%%i&i(ation

(ontent and re(o))end )ana+e)ent * a %'e(iaiKed tea) at

t#e )eta- %tati( %ta+e.

>$i%#ed iterat$re on #ead and ne(H a%o ado't% t#e

AJ "5@ (a%%i&i(ation &or %Hin (an(er%.

"#$%, a%ed on a 'ro%'e(tie %t$d* inoin+ 8R 'atient% Git#

'arotid )eta%ta%i% o& &ooGed $' &or a )ini)$) o& 2

*ear%, OJBrien100

'er&or)ed a )$tiariate ana*%i%

de)on%tratin+ t#at 'atient% Git# (eri(a and 'arotid >

)eta%ta%e% #ad a Gor%e 'ro+no%i% t#an t#o%e Git# 'arotid

)eta%ta%e% aone, t#at 'arotid ina%ion Ga% an inde'endent

'redi(tie (riterion &or o(a re($r- ren(e, and t#at %ta+e 5 Ga%

an inde'endent 'redi(tie'ara)eter

&or %$ria ee o& eiden(e 2.OBrien 'ro'o%ed t#e &ooGin+ (a%%i&i(ation, taHin+ into

a((o$nt 'arotid +and %tat$%:

>arotid: >1 node )eta%tati( 3 () in dia)eterN

M >2: 3 () ^)eta%tati( node 6 () in dia)eterN

M >3: )eta%tati( node `6 (), 'ara*%i% o& &a(ia nere, or

ina%ion o& a%e o& %H$.

5e(H: 50: no (eri(a %iteN

M 51: #o)oatera )eta%tati( *)'# node 3 () in dia)eterN

M 52: )eta%tati( *)'# node `3 () in dia)eter or )$ti'e

or (ontraatera.

Ce(o))endation%

>ro+no%ti( ea$ation o& *)'# node %tat$% )$%t taHe into

a((o$nt:

M t#e n$)er and %iKe o& *)'# node% inadedN

M t#e 're%en(e or a%en(e o& extra(a'%$ar ina%ion.

A% t#e )ajorit* o& *)'# node )eta%ta%e% %een area%%o(iated Git# #ead and ne(H , t#e Q 'ro'o%e% to

ado't, in t#e%e (a%e%, t#e (a%%i&i(ation (riteria n$)er, %iKe and

%ite o& )eta%ta- %e% &or #ead and ne(H (ar(ino)a%.

III.4.3. Di%tant )eta%ta%e% "#e on%et o& di%tant )eta%ta%e% (ar-

rie% a &ata 'ro+no%i% in t#e %#ort- to )edi$)-ter).

IV. "reat)ent )et#od% &or and 're($r%or

e%ion%

IV.1. "reat)ent )et#od% &or 're($r%or e%ion% o&

IV.1.1. $r+er* In t#eor*, %$r+i(a treat)ent o& 're($r%or%

)a* e eni%a+ed, and i% a%ed on %tandard %$r+er* Git# )ini)a

)ar+in%. It i% $%ed exten%ie* in BoGenJ% di%ea%e, G#ere it #a%

t#e adanta+e o& enain+ #i%to'at#oo+i(a eri&i(ation o& t#e

dia+no- %i% and t#e a%en(e o& ina%ion. oGeer, t#ere i% a

%tron+ 're&eren(e in %o)e $arter% &or )edi(a and '#*%i(a

)et#od%, 'arti($ar* in t#e treat)ent o& A. "#e a$e o&

%$r+er* #a% not een ea$ated in (o)'ari%on Git# t#e atter

)et#od%.

IV.1.2. De%(ri'tion o& )edi(a and '#*%i(a treat)ent

)et#od%

IV.1.2.1. r*ot#era'* and (r*o%$r+er*

"#e%e )et#od% inoe ti%%$e de%tr$(tion * a''i(ation o&

extre)e (od $%in+ i$id nitro+en. In t#e En+i%# %(ienti&i(

itera- t$re, t#e ter)% T(r*ot#era'* and T(r*o%$r+er* are o&ten

$%ed inter(#an+ea* Git#o$t %'e(i&*in+ t#e a(t$a )et#od $%ed.

r*ot#era'* inoe% a'oriKin+ i$id nitro+en on a e%ion to

&reeKe it. "#i% a''roa(# de%tro*% %$'er&i(ia ti%%$e. r*ot#era'*

i% a %i)'e, ra'id and inex'en%ie )et#od, 'roided t#ere i%

ea%* a((e%% to a 'ra(titioner in +enera, a der)atoo+i%t. "#e

o'ti- )$) d$ration o& &reeKin+ i% not HnoGn, $t t#e oGe%t

rate% o& re($rren(e are otained $%in+ Ta++re%%i9e 'roto(o%.

eera (r*o- t#era'* %e%%ion% )a* e needed.r*ot#era'* re$ire% ro$tine (ontro o& t#era'e$ti( e&&i(a(*,

and (arrie% a ri%H o& dee' 'i+)ented %(ar%.

r*o%$r+er* i% $%ed &or dee'er e%ion%. "o t#i% end, (od i% di&-

&$%ed a(ro%% t#e t#i(Hne%% o& t#e %Hin &ooGin+ a''i(ation o& a

(od ee(trode $nder o(a anae%t#e%ia. "#e de+ree o& &reeKin+ i%

(ontroed $%in+ an i)'edan(e )etre. oGeer, t#ere are er*

&eG %t$die% in G#i(# t#e a$e o& t#i% t#era'e$ti( a''roa(# &or

A and BD #a% een a%%e%%ed.


20/56

IV.1.2.2. $retta+e and (a$ter*

"#i% de%tr$(tie te(#ni$e, 'er&or)ed $nder o(a

anae%t#e%ia, (o)ine% ($retta+e o& t#e e%ion and (oa+$ation

Git# an ee(tri( %(a'e. "#e te(#ni$e i% ra'id and aoG% &or

#ae)o%ta%i%, een in'atient% on anti(oa+$ant dr$+%. In


21/56

inoed in e'it#eia t$)o$r +roGt#. Di(o&ena(, $%ed in t#e

treat)ent o& A a% tGo a''i(ation% 'er da* &or 23 )ont#%,

i% Ge toerated.

IV.1.2.R. >#otod*na)i( t#era'* >D"

>D" inoe% ad)ini%tration o& a '#oto%en%itiKin+ 'rod$(t *

t#e to'i(a ro$te. "#i% re%$t% in t#e a(($)$ation o&

'#otorea(tie 'or'#*rin% in t$)o$r (e%. >#otoa(tiation o&

t#e%e (e%, $%in+ a %$itae i+#t %o$r(e, ead% to a'o'to%i% and%ee(tie ne(ro%i% o& t$)o$r (e%, Git# %'arin+ o& #eat#*

adja(ent ti%%$e.

One t$e o& -)et#*a)inoe$inate @A @etixia

168 )+ L+ (rea) i% %$&&i(ient to treat an area o& aro$nd 22 ()2.

In 'ra(ti(e, t#e to'i(a (rea) i% $%ed a&ter ($retta+e. "#e

'#oto%en%i- tiKin+ 're'aration i% a''ied to t#e re+ion to e

treated 3 #o$r% 'rior to irradiation and t#en 'a(ed $nder

o(($%ie anda+in+. Irradiation )a* e ad)ini%tered $%in+

ario$% t*'e% o& a)', )o%t (o))on* a red a%er at 63 n).


22/56

Ga% in&erior, and t#e 1-*ear rea'%e rate Ga% #i+#er in t#e (r*ot#er-

a'* +ro$' ee o& eiden(e 2.

e* 'oint%

r*ot#era'* i% t#e re&eren(e treat)ent &or A in der)atoo+i(a

'ra(ti(e, de%'ite t#e exi%ten(e o& er* &eG (o)'aratie %t$die%

on t#i% to'i(.

r*ot#era'* i% a %i)'e, ra'id and inex'en%ie )et#od, 'ro-

ided a %'e(iai%t i% at #and.

It )a* e $%ed a% &ir%t-ine treat)ent, de%'ite t#e &a(t t#at it%

e&&i(a(*, G#i(# i% ar+e* o'erator-de'endent, )a* e in&erior to

t#at o& (#e)i(a treat)ent%.

O2 a%er

A((ordin+ to t#e 200R BAD +$ideine%, O2 a%er, iHe ot#er

%o$r(e% o& de%tr$(tie ener+*, (an e $%ed &or A treat)ent,

at#o$+# t#ere i% itte data a% to t#e e&&i(a(* o& t#i% treat)ent

ee o& e9iden(e 4.

In a retro%'e(tie %t$d* inoin+ 31 'atient%, 8X 're%ented no

re($rren(e d$rin+ a )ean &ooG-$' 'eriod o& 2 *ear%.120

C 3

LGHL16GH

3LGHL4GH2nd

%e%%ion4GH

8GH

"aDeR

I)i$i)

od%t$d*re%$t%

/t$d*t*'e

5tota

5

L+ro$'

44

C/%.>B

C/%.>B

)$ti(entre

C/%.>B

)$ti(entre

nS29

L130

>B

A$t#or

ear

04

eDGo#

2004

anAo)ar

200R


23/56

%L GeeH doe% not di)ini%# e&&i(a(*. raGt(#enHo et a.,112

(o)-'arin+ i)i$i)od a''ied t#ree ti)e% 'er GeeH &or 4

GeeH%, (r*o%$r+er* 2040 % 'er e%ion and -atient% Gere &ooGed $'

at 1, 4 and 24 GeeH%. D"

"#e 5@C and BAD +$ideine%, '$i%#ed in 2002,

're%ent

>D" a% a treat)ent 'ro)i%in+ +ood ae%t#eti( re%$t%, G#i(#i%

A (a%e% o& t#e &a(e and %(a' in 119 'atient% Gere treated, and

intra-indiid$a @A->D" Ga% (o)'ared Git# (r*ot#era'*.

"#e 'er(enta+e rate o& (o)'ete A re+re%%ion at 12 GeeH% in

t#e 'er 'roto(o >> 'o'$ation Ga% etter &or >D" 86.9X

t#an &or (r*ot#era'* R6.2X, Git# %i)iar re%$t% o%ered at

24 GeeH% 89.1X %. 86.1X. o%)eti( re%$t% &or >D" in t#e >>

'o'$ation Gere a%o etter a((ordin+ to 'atient% and a%%e%%or%

aiHe re%$t% Gere Tex(eentJ at 12 and 24 GeeH%: R0.8X and

RR.2X %. R.4X and 49.RX &or (r*ot#era'*. a&et* Ga%

(on%idered +ood &orot# treat)ent% "ae 8.

e* 'oint%

"#e e&&i(a(* o& >D" i% +oa* (o)'arae Git# t#at o& (r*ot#er-

a'* and -


24/56

"ae 8 Di(o&ena( %t$d* re%$t%

A$t#or *ear t$d* t*'e 5o. %$je(t%L +ro$' "reat)ent )odait* >C: di(o L >B or ot#er a&et*

Qo& 2001 C %. >B 96 46 di(o L 2 >B 2_L d &or 90 d 4R L 19X at 4 )ont#% o)'arae

B 20 2_L d &or 3 )ont#% 9 L 0X at 3 )ont#%

Cier% 2002 C %.>B,

)$ti(entre 19 2_L d &or 30 d:49 >B L 49 di(o2_L d &or 60 d:

49 >B L 48 di(o

1R L X at 30 d31 L 10X at 60 d

ea$er 2003 C %. >B 11 0 di(o L 6 'a(eo 2_L d &or 90 d 38 L 10X at 4 )ont#%

)it# 200R o)'aratie

di(o L -


25/56

Bar+)an121

de)on%trated t#e on+-ter) e&&i(a(* o& o(a -

D"

A((ordin+ to t#e 2006 BAD +$ideine%,121

>D" *ied%

e$iaent or %$'erior re%$t% to (r*ot#era'* and -


26/56

Ce(o))endation%

-D" )a* e 'ro'o%ed in BD G#en %$r+er* i% (o)'i-

(ated d$e to exten%ie or )$ti'e e%ion%, or G#en e%ion %ite%

are in area% Git# 'oor Go$nd #eain+ +rade B.

"#ere i% in%$&&i(ient data to re(o))end (r*ot#era'*,

'arti($- ar* a% &ar a% area% Git# 'oor Go$nd #eain+ are

(on(erned.

5o re(o))endation% (an e &or)$ated re+ardin+ t#e $%e o&

a%er, ($retta+e and (a$ter* in BD.

IV.2. $r+i(a treat)ent o& in&itratin+

$r+er* i% $nani)o$%* re(o+niKed in t#e ada'ted BAD, 55

and 5@C +$ideine% a% t#e treat)ent o& (#oi(e &or

t#e%e t$)o$r%. It #a% t#e adanta+e o& 'roidin+ ex(i%ion ti%%$e,

G#i(# enae% #i%too+i(a (on&ir)ation o& dia+no%i% and

eri&i(ation o& ex(i%ion $ait*, a% Ge a% a(#iein+ extre)e*

#i+# rate% o& o(a (ontro and ($re in t#e a%t )ajorit* o&

'atient%.

It re)ain% t#e +od %tandard a+ain%t G#i(# a non-%$r+i(a

treat)ent% &or )$%t e (o)'ared.12

IV.2.1. tandard %$r+er*

IV.2.1.1. Ai)% o& treat)ent

"#e )ain ai) o& %$r+i(a treat)ent &or i% to otain

(o)'ete and #i%too+i(a* (on&ir)ed t$)o$r ex(i%ion.

"#ere are tGo ot#er reeant +oa%:

M )aintenan(e o& nor)a &$n(tion a% &ar a% 'o%%ieN

M %ati%&a(tor* (o%)eti( re%$t%.

"#i% re$ire)ent o& re%e(tion in %ano &ooGed * &$n(tiona

and (o%)eti( re(on%tr$(tion i% 'arti($ar* i)'ortant &or t#e

&a(e, e%'e(ia* &or e%ion% near nat$ra ori&i(e%.

>ri)ar* ex(i%ion, G#en 'er&or)ed 'ro'er*, re%$t% in ($re rate%

in ex(e%% o& 90X.83,126

IV.2.1.2. enera 'rin(i'e% o& %$r+i(a treat)ent

"#e%e are %et o$t in detai * t#e 5@C,12

and t#e Q

ado'ted t#e &ooGin+re(o))endation%:

M >atient% )$%t e &$* in&or)ed 'rior to a %$r+i(a a(t%. "#i%

in&or)ation (o)'ri%e% t#era'e$ti( o'tion%, ot# %$r+i(a

and non-%$r+i(a, t#e ri%H% and 'otentia %e$eae inoed,

a% Ge a% t#e ene&it% and re%$t% ex'e(ted in t#e %#ort- and

on+-ter) Git# re%'e(t to &$n(tiona and (o%)eti( o$t-

(o)e%. "#e 'atient )$%t e in&or)ed t#at ti%%$e re)oed

d$rin+ ex(i%ion Gi $nder+o #i%to'at#oo+i(a ana*%i%, and

t#at &$rt#er %$r+er* )a* e ne(e%%ar* de'endin+ on t#e

re%$t% o& t#i% ana*%i% in t#e eent o& in(o)'ete ex(i%ion.M I& t#ere are (ini(a do$t% ao$t t#e dia+no%i%, #i%too+i-

(a (on&ir)ation i% ne(e%%ar*. "#i% Gi re$ire a io'%*

* '$n(# io'%* or %$r+er* e&ore t#e )ain ex(i%ion, or

(o)'ete ex(i%ion in t#e (a%e o& %)a e%ion% t#at are ea%*

to re)oe and re'air.


27/56

M B* de&inition, io'%ie% on* aoG &or 'artia %t$d* o&

e%ion%, and an* data )$%t e (o)'eted * ana*%i% o&

ti%%$e re)oed d$rin+ %$r+er*.

M "#e %$r+i(a 'ro(ed$re )$%t e 'anned in a((ordan(e

Git# t$)o$r 'ara)eter%. "#e atera and dee' order%

de+ree o& in&itration o& t#e e%ion )$%t $nder+o (are&$

(ini(a ea$ation. Ex(i%ion )ar+in% )$%t e )arHed'rior

to t#e inje(tion o& o(a anae%t#eti( a+ent%, a% t#e atter

(o$d )aHe t$)o$r )ar+in% )ore di&&i($t to di%(ern.

M Exten%ie t$)o$r re%e(tion inoin+ (o%)eti(a* or

&$n(tiona* %en%itie area% 'artia %a(ri&i(e o& an e*eid

or tear d$(t, o'eration% inoin+ t#e &a(e, i'%, na%a '*r-

a)id and +enera* an* o'eration re%$tin+ in exten%ie

o%% o& &e%# &ooGed * re(on%tr$(tion re$ire% %$r+i(a

ex'erti%e in %Hin (an(er )ana+e)ent.

M $r+er* on 'eriori&i(ia o& t#e &a(e, i'% and ear%, a%

Ge a% Git# 'erine$ra ina%ion %#o$d e $nder-

taHen &ooGin+ ID, G#eneer it i% di&&i($t to en%$re

%'arin+ o& t#e %tandard )ar+in% Git#o$t a&&e(tin+ (o%-)eti( or &$n(tiona 'ro+no%i% 'ro&e%%iona (on%en%$%.

M >o%to'eratie radiot#era'* i% o((a%iona* ne(e%%ar* %ee

eoG.

IV.2.1.3. Ex(i%ion )ar+in%

"#e )ar+in o& #eat#* %Hin t#at need% to e re)oed to en%$re

(o)'ete t$)o$r eradi(ation i% t#e (r$(ia $e%tion in %$r+i(a

treat)ent and t#e )ain to'i( o& di%($%%ion.12,12R

"#e 2002 BAD and 55 +$ideine% re&er to Brodand and

]itei12

G#o, a%ed on a 'ro%'e(tie %t$d* inoin+ 141 (a%e%

o& 'ri)ar* re)oed * @o#% %$r+er*, noted t#at:

Ma 4-)) )ar+in i% %$&&i(ient to eradi(ate 9X o&

t$)o$r%

)ea%$rin+ e%% t#an 2 () in dia)eterN

M a )ar+in `6 )) i% ne(e%%ar* to otain t#e %a)e re%$t

&or t$)o$r% o& dia)eter `2 () or &or t$)o$r% a%%o(iated

Git# ri%H &a(tor%, %$(# a% 'oor* di&&erentiated ,

inadin+ %$($taneo$% ti%%$e or o(ated in area% at

ri%H ee o& eiden(e 2.

It i% i)'ortant to note t#at t#e ex(i%ion )ar+in %#o$d e

in(rea%ed to 10 )) or )ore to otain %i)iar ee% o& o(a

(ontro $nder (ertain (ir($)%tan(e%: &$rt#er ex(i%ion &ooGin+

'o%i- tie 'o%to'eratie (ontro o& t#e )ar+in% or t$)o$r

(#ara(teri%ti(% a%%o(iated Git# ri%H o& %$(ini(a exten%ion, %$(#

a% #i+# #i%too+i- (a +rade, ina%ion o& t#e #*'oder)i%,

o(ation in area% at ri%H and, a &ortiori, in (a%e% o& 'erine$raina%ion.


28/56

t#ere are no &$rt#er t$)o$ra &o(i, t#e )ar+in% are (on%idered to

e #eat#*. Ot#erGi%e, t#e re%id$a t$)o$r i% )arHed to aoG

&or &$rt#er ex(i%ion, G#i(# i% (arried o$t in 'arae to t#e area

&ro) G#i(# ti%%$e #a% een re)oed. $(# ex(i%ion in %$((e%%ie

%i(e% re$ire% (o%e (o-ordination etGeen %$r+er*, %e(tion

're'aration and #i%too+i(a ana*%i%. oGeer, it in(rea%e%

o'eratin+ ti)e% and inoe% )ore %ta&&, t#ere* in(rea%in+

treat)ent (o%t%.

Qit# ot#er t*'e% o& )i(ro+ra'#i( %$r+er*, @o#%

@i(ro+ra'#i( $r+er* @@ Git# in($%ion in a 'ara&&in o(H

%oG @o#% or %i)iar a''roa(#e% Bre$nin+er and ot#er%,

#i%too+* re%$t% are not i))ediate* aaiae, a% t#e ti%%$e i%

in($ded in 'ara&&in. At#o$+# t#e a%en(e o& exte)'oraneo$%

#i%too+i(a ana*%i% red$(e% t#e (o%t, t#i% re)ain% a (o)'ex

o'eration inoin+ )in- $te exa)ination o& t#e ex(i%ed ti%%$e *

t#e #i%to'at#oo+i%t.

IV.2.2.2. Biio+ra'#i(a ana*%i%

BAD +$ideine%9

@@ en%$re% (o)'ete ex(i%ion o& a t$)o$r ex'andin+ &ro) a

%in+e %ite * adj$%tin+ ti%%$e re)oa in a((ordan(e Git#

%$(ini- (a %'read. @@ %#o$d e (on%idered in t#e treat)ent

o& #i+#- ri%H . It i% 'arti($ar* re(o))ended in (a%e%

G#ere t#e $naoidae (reation o& road ex(i%ion )ar+in% (o$d

(a$%e &$n(- tiona i)'air)ent. "#e e%t ($re rate% &or #i+#-

ri%H #ae een otained in 'atient %erie% treated Git#

@@.82

I& @@ i% not aaiae in t#e%e indi(ation%, t#e %$r+i(a

aternatie i% %tandard ex(i%ion Git# a )ar+in 6 )), Git#

#i%to'at#o- o+i(a (ontro o& t#e 'erit$)ora ed+e%.129

oGeer, t#ere are no 'ro%'e(tie rando)iKed %t$die%(o)'arin+ t#e re%$t% o& %tandard ex(i%ion to t#o%e o& @@.

55 +$ideine%8

@@ )$%t e (arried o$t * a trained tea). It i% indi(ated

in ot# #i+#-ri%H , G#ere it i% t#e treat)ent o& (#oi(e, and

oG- ri%H , G#en t#e )ar+in te%t% 'o%itie a&ter %tandard

ex(i%ion o&

46 )). "#e aternatie% to @@ are %$r+i(a ex(i%ion

&ooGed * (o)'ete (ir($)&erentia, 'eri'#era and dee'

)ar+in a%%e%%- )ent, or %tandard %$r+er* Git# %tandard )ar+in%

o& 10 )).5@C +$ideine%R

@@ i% e%'e(ia* %$itae in (a%e% G#ere (o)'ete ex(i%ion i%

di&- &i($t to a(#iee, and in (a%e% Git# a #i+#er t#an nor)a

ri%H o& re($rren(e. "#e indi(ation% ado'ted are o(ated on

t#e (entra &a(ia re+ion or 'eriori&i(ia area%, a% Ge a%

re($rren(e or in(o)'ete ex(i%ion, Git# (ini(a and #i%too+i(a

(#ara(teri%ti(% o& #i+#-ri%H t$)o$r.

"#e adanta+e% o& @@ ie in t#e %'arin+ o& #eat#* ti%%$e,

it% er* #i+# ($re rate, t#e (ertaint* o& (o)'ete ex(i%ion aoGin+

&or (on&ident re(on%tr$(tion a% Ge a% t#e o'tion o& o'eratin+

$nder o(a anae%t#e%ia.

"#e draGa(H% o& @@ in($de t#e d$ration and (o%t o& t#e

'ro(ed$re, a% Ge a% t#e need &or trained and ex'erien(ed %ta&&.

Ana*%i% o& additiona'$i(ation%

eioit(# I et a.131

re'orted t#e re%$t% o& a 'ro%'e(tie

)$ti(en-tre %t$d* inoin+ 1,263 (a%e% 19932002, o& G#i(#

61.1X

Gere 'ri)ar* and 38.9X re($rren(e%.


29/56

t$)o$r ti%%$e and nor)a adja(ent ti%%$e re%i%tant to ($retta+e. It

(o)'ri%e% one or )ore (*(e% o& %(ra'in+ $%in+ a ($rette, $nder

o(a anae%t#e%ia, &ooGed * &reeKin+ Git# an ee(tri( %(a'e.

"#e 'ro(ed$re i% ra'id, %'are% %Hin ti%%$e, enae% #ae)o%ta%i%,

een in'atient% on anti(oa+$ant t#era'* and i% inex'en%ie.

A %t$d* o& ($retta+e %#ain+% (an 'roide #i%too+i(a

(on&ir)a- tion o& dia+no%i%, $t doe% not aoG &or )ar+in

(ontro. "#i% a''roa(# re$ire% (ertaint* o& (ini(a dia+no%i%,

Ge-deineated t$)o$r ed+e%, %$r&a(e exten%ion a% Ge a% a

trained o'erator.

"#e 55 +$ideine% i%t tGo 'roi%o% &or $%in+ t#i%

te(#ni$e: >iar re+ion% are not %$itae a% t$)o$r% %'readin+

aon+ 'iar %#eat#% are not aGa*% (a$+#t * t#e ($retteN t#e

te(#ni$e i% ina'- 'ro'riate &or e%ion% inoin+ t#e

#*'oder)i%, e(a$%e in t#i% area, t#e o'erator i% $nae to

di%tin+$i%# etGeen t#e (on%i%ten(* o& t$)o$r% and t#at o&

#eat#* ti%%$e.

"#e 5@C +$ideine% %i)'* note t#at itte data are

aaiae in t#e iterat$re (on(ernin+ t#e a$e o& t#i% )et#od,$t 'oint o$t Git#o$t 'ro'o%in+ an* re(o))endation% on

t#i% %$je(t t#at t#e te(#ni$e i% $%ed in t#e treat)ent o& ,

BD and Hera- toa(ant#o)a.

In re%entation o& t#e te(#ni$e Cadiot#era'* C" (on-

%i%t% o& t#e $%e o& ioniKin+ radiation in t#e treat)ent o& (an(er

ia tGo )ain )odaitie%: externa radiot#era'* and inter%titia

($rie- t#era'*.

IV.3.1.1. Externa radiot#era'*

"#i% )odait* $%e% oG-ener+* W '#oton% (onta(t W-ra* t#era'*,

#i+#-ener+* W '#oton%, +a))a ra*% tee(oat or ee(tron

ea)% inear a((eerator%. It i% a non-ina%ie &or) o&

treat)ent t#at )a* e $%ed in irre%'e(tie o& %iKe or de't#. A

n$)er o& %e%- %ion% )ean: 1030 are re$ired oer a 'eriod o&

36 GeeH%. Do%e &ra(tionation a(#iee% etter (o%)eti( re%$t%

G#ie in(rea%in+ treat)ent ti)e. "#i% &a(tor )$%t e taHen into

a((o$nt in eder*


30/56

'atient% or 'atient% iin+ &ar &ro) t#e treat)ent (entre. "#e'ra(-

titioner )$%t taHe into (on%ideration t#e radiation ($re re+ardin+

de't# and &or t#e 'en$)ra aro$nd t#e a(t$a radiation

&ied, de'endin+ on t#e t*'e o& ener+* $%ed.

A %a&et* )ar+in o& 11. () aro$nd t#e t$)o$r i%

re(o)- )ended e(a$%e o& t#e ri%H o& )i(ro%(o'i(

di%%e)ination and $n(ertaint* ao$t 'atient )oe)ent

t#ro$+#o$t deier*.

A($te %e(ondar* e&&e(t% %$(# a% e'ider)iti% o(($r 23

GeeH% a&ter t#e %tart o& treat)ent %e%%ion% and are reer%ie

Git#in %e- era da*% to %eera GeeH%.

ate %ide-e&&e(t% o(($rrin+ %eera )ont#% or *ear% a&ter

treat- )ent are irreer%ie and in($de ($taneo$% atro'#* Git#

#air o%%, red$(tion o& %Geat and %ea(eo$% %e(retion, d*%(#ro)ia

#*'o'i+- )entation or #*'er'i+)entation, tean+e(ta%ia a%

Ge a% der)a or #*'oder)a %(ero%i%. "#e%e e&&e(t% are

(ontin$a* eoin+,$t d$e to (o)'$teriKed do%e (a($ation,

it %#o$d e 'o%%ie to aert t#e '#eno)enon o& radione(ro%i%.

Cadiot#era'* ex'o%e% 'atient% to t#e ri%H o& a %e(ond(ar(ino)a in t#e irradiated area, and i% (ontraindi(ated in er*

rare (a%e% o& +enoder)ato%i% 'redi%'o%in+ to %Hin (an(er.


31/56

IV.3.2.2 Indi(ation% &or radiot#era'* a((ordin+ to (ini(a %it$ation

>reio$%* $ntreated

Externa radiot#era'*R9,138141

and inter%titia ($riet#era'*14214

*ied re%$t% (o)'arae Git# t#o%e o& %$r+er*, Git# ee% o&

o(a (ontro at *ear% o&:

M 929RX &or "1 t$)o$r%N

M 68X &or "2 t$)o$r%N

M 060X &or "3-4 t$)o$r% on t#e "5@ (a%%i&i(ation.

5I or exten%ie (ini(a rea'%e are R8

8RX and

0Xre%'e(tie*.

R,1

Adj$ant radiot#era'* )a* e eni%a+ed in t#e (a%e o& exten%ie

>5I, 'rin(i'a* aro$nd t#e a%e o& t#e

%H$.R,8,1


32/56

@eta%tati(

In t#e (a%e o& *)'# node inoe)ent, %$r+i(a re%e(tion )a*

e 'ro'o%ed a% &ir%t-ine treat)ent BAD 2002, 5C@,

55. "#e ee o& o(a (ontro &ooGin+ (o)ined treat)ent

%$r+er* adj$ant externa C" in t#e eent o& 'arotid *)'#

node ina%ion i% aro$nd 80X %. 300X &ooGin+ %in+e-

)odait* treat)ent %$r+er* or externa C" Git# rea'%e-&ree

%$ria at *ear% o&

R0X %. 0X.

16161

Ce(o))endation%

i%too+i(a (on&ir)ation o& dia+no%i% i% re$ired e&ore e+in-

nin+ C" )ana+e)ent o& .

Cadiot#era'* %#o$d e $%ed on* &or a )inorit* o& 'ri)ar*

G#i(# 'o%e %'e(ia 'roe)% Git# re+ard to %tandard

%$r+er*, and &or Git# 'oor 'ro+no%i% re($rrin+ or

adan(ed , G#ere %$r+i(a treat)ent )a* e (o)ined Git#

radiot#er- a'* to i)'roe t$)o$r (ontro +rade B.

Q#en radiot#era'* i% indi(ated, it )$%t e adj$%ted and

)od$- ated in a((ordan(e Git#:

M 'atient a+e, a$tono)* and di%tan(e &ro) treat)ent (entreN

M %ite and %iKeN

M aaiaiit* and t*'e o& te(#ni(a e$i')ent 'roided *

t#e radiot#era'* $nit.

Cadiot#era'* i% not re(o))ended a% &ir%t-ine treat)ent in

t#e &ooGin+ (a%e% 'ro&e%%iona (on%en%$%:

M G#ere %$r+i(a ex(i%ion i% 'o%%ieN

M in (ertain area% %$(# a% #and%, &eet, e+% or +enita or+an%

Git# t#e %oe ex(e'tion o& ($riet#era'* &or 'enie .

Cadiot#era'* )a* e di%($%%ed in d$e (o$r%e and 'ro'o%ed a%

&ir%t-ine treat)ent in t#e &ooGin+ (a%e% +radeB:

M G#ere %$r+er* i% not 'o%%ie (ontraindi(ation, 'atient

re&$%aN

M G#ere %$r+er* (o$d (a$%e )ajor &$n(tiona or )or'#o-o+i(a 'roe)% na%a a)'$tation, %$r+er* o& t#e inter-

na o($ar (ant#$%, aia re%e(tion, (o))i%%$ra aia

re%e(tion and exten%ie &a(ia Git# o%% o& %$%tan(e

or %a(ri&i(e o& &a(ia nere, a&ter t#e 'atient #a% een

in&or)ed, and t#e adanta+e% and di%adanta+e% o& ea(#

)et#od #ae een di%($%%ed in ter)% o& on(oo+i(a,

&$n(tiona and )or'#oo+i(a re%$t%.

Adj$ant radiot#era'* i% indi(ated in t#e &ooGin+ (a%e%

+rade B:

M in(o)'ete )i(ro%(o'i( ex(i%ion Git# no 'o%%iiit* o&

&$rt#er %$r+er*N

M Git# exten%ie 'erine$ra ina%ionN

M )eta%tati( *)'# node ina%ion.

IV.4. *%te)i( (#e)ot#era'* in

#e)ot#era'* i% o& i)ited a$e, ein+ $%ed on* in

(a%e% o& &aied %$r+er* or radiot#era'*, G#ere t#e%e

treat)ent% are


33/56

inade$ate or #ae een $ndertaHen too ate. In t#e 5C@

+$ideine%, (i%'atin i% t#e re&eren(e (#e)ot#era'*. "#e

iterat$re on t#i% %$je(t i% er* %(ant and (ontain% on* a &eG

%)a %erie% aon+ Git# n$)ero$% i%oated (a%e%.162163

"#e

on* (ontroed %t$die% (on(ern #ead and ne(H )o$t#,

'#ar*nx and ar*nx, $t t#e%e (annot e &$* a%%i)iated to

.

eera di&&erent t*'e% o& (#e)ot#era'* o'tion% exi%t.

IV.4.1. >reo'eratie .neoadj$ant0 (#e)ored$(tion 5eoadj$ant

(#e)ot#era'* #a% een $%ed in er* ar+e t$)o$r% to render

t#e) a)enae to %$r+er*. A% t#e )ajorit* o& %t$die% #ae

%#oGn no i)'roe)ent in t$)o$r (ontro or %$ria, t#i%

treat)ent )et#od i% rare* $%ed.

"#er)o(#e)ot#era'* o& an i%oated i) #a% een 'ro'o%ed a%

neoadj$ant t#era'* in%tead o& 'aiatie %*%te)i( (#e)ot#era'*

in adan(ed (ar(ino)a% o& t#e i)%. "#e %$%tan(e% $%ed are

)e-'#aan and doxor$i(in, eit#er aone or in (o)ination Git#

(i%- 'atin. "#i% )et#od, t#at i% te(#ni(a* er* de)andin+, i%'o%%ie on* &or #i+#* trained tea)%, a% it inoe% non-

ne+i+ie re+iona ri%H% *)'#oede)a, '#eiti% t#at )a* on

o((a%ion e %erio$% arteria di%%e(tion, exten%ie ($taneo$%

ne(ro%i% or %$'er-in&e(- tion. o)ination o& "5aiatie (#e)ot#era'* and (#e)o-radiot#era'*

>aiatie (#e)ot#era'* i% re%ered &or &or)% o& t#e di%ea%e

G#i(# are ino'erae &ro) t#e o$t%et d$e to o(o-re+iona

exten%ion, and

&or )eta%tati( &or)%. It )a* a%o e $%ed in (o)ination Git#

radiot#era'*, 'roided t#e 'atient% +enera #eat#, G#i(# i% o&ten

#i+#* (o)'ro)i%ed, aoG% &or t#i%.

Dr$+% (on%idered a(tie in t#i% (a%e are (i%'atin,164

eo)*(in,

-&$oro$ra(i, )et#otrexate and adria)*(in. "#e #i+#e%t re%'on%e

rate% aro$nd 80X #ae een otained Git# (o)ined treat)ent%

%$(# a% (o)ined (i%'atin D1, 100 )+L )2, -&$oro$ra(i

D1 to D, 60 )+ L)2L d and eo)*(in D1 to D, 16 )+ L

)2

L d. o)'arae re%$t% #ae een otained * (o)inin+

(i%'atin or (aro'atin Git# taxane%, +e)(itaine or

i&o%&a)ide. o)'ete re)i%%ion i% rare and &re$ent* tran%ient.

5o %t$die% #ae de)on- %trated in(rea%ed %$ria &or

'o*(#e)ot#era'* (o)'ared Git# (i%'atin aone.

eera %t$die% and )eta-ana*%e% o& (o)ined t#era'* ino-

in+ 'aiatie (#e)ot#era'*-radiot#era'* in )$(o%a o& t#e

#ead and ne(H #ae ex#iited %$'erior %$ria rate% in reation

to radiot#era'* aone, $t at t#e 'ri(e o& in(rea%ed toxi(it*

)$(o%a, ne$roo+i(a, +a%trointe%tina, )ed$a and rena. "#e

dr$+% $%ed Gere (i%'atin aone, -


34/56

It )a* e 'ro'o%ed in ID &or ino'erae &or)% &ro) t#e o$t%et

d$e to o(o-re+iona %'read, and in )eta%tati( &or)%, 'o%%i*

in (o)ination Git# radiot#era'*, 'roided t#e 'atientJ% +enera

#eat#, G#i(# i% $%$a* #i+#* (o)'ro)i%ed, 'er)it% t#i%

'ro&e%- %iona (on%en%$%.

"#e $%e o& )ono(ona antiodie% )a* (on%tit$te an intere%tin+t#era'e$ti( o'tion, $t t#i% a''roa(# i% ($rrent* $nder ea$a-

tion.

V. @ana+e)ent o& and 're($r%or e%ion%

V.1. >reention

V.1.1. >ri)ar* 'reention On%et o& i% dire(t* a%%o(iated

Git# %$n ex'o%$re and i% t#ere&ore de'endent on atit$de and

i&e- %t*e. "#e %t$d* o& A$%traian i))i+rant% %#oGed t#at

ex'o%$re d$rin+ (#id#ood and adoe%(en(e 'a*ed an i)'ortantroe in t#e e)er+en(e o& . "#i% $nder%(ore% t#e %i+ni&i(an(e

o&'rote(tion a+ain%t %$n ex'o%$re at t#e%e %ta+e% o& i&e, at#o$+#

it i% %ti ne(e%- %ar* to i)it %$n ex'o%$re in ad$t%. >reention

'ro+ra))e% )$%t tar+et %(#oo (#idren and adoe%(ent% Git#

e)'#a%i% on da)a+e (a$%ed to t#e %Hin rat#er t#an on t#e ri%H o&

(an(er.

A% &or t#e 'reention o& )eano)a, in&or)ation and adi(e

ai) to 'ro)ote rea%onae e#aio$r Git# re+ard to %$n

ex'o%$re aon+ Git# %$itae'#oto'rote(tion,101,102

G#i(# %#o$d

e (ontin- $ed t#ro$+#o$t i&e, 'arti($ar* in 'atient% at ri%H

i+#t %Hin '#o- tot*'e, and 'ro&e%%iona or re(reationa %$n

ex'o%$re, *:

M aoidin+ ex'o%$re to t#e )idda* %$n etGeen 11.00 a)

and 3.00 '): 60X o& t#e %$n% dai* ener+* rea(#e% t#e

eart# d$rin+ t#e%e ti)e%N

M re)ainin+ in t#e %#ade a% )$(# a% 'o%%ieN

M Gearin+ 'rote(tie (ot#in+ %$(# a% road-ri))ed #at%,

"-%#irt%, %$n+a%%e%, et(.

$n%(reen% (on%tit$te a a%t ine o& 'rote(tion: index #i+#er t#an

20, road-%'e(tr$), Gater-re%i%tant and a''ied eer* 2 #o$r%.

$n%(reen% do not aoG &or ex'o%$re ti)e% to e in(rea%ed.

QindoG +a%% o& a t#i(Hne%% o& 3 )) 'roide% a 'rote(tie

index o& 14 &or VB,$t not a+ain%t VA.

"#e $%e o& %$n a)'% and tannin+ (ain% %#o$d e i)ited, a%

t#i% doe% not red$(e t#e ri%H, $t rat#er in(rea%e% t#e a)o$nto& radiation re(eied.

V.1.2. e(ondar* 'reention "#ere i% no (on%en%$% on ro$tine

%(reenin+ in t#e +enera 'o'$ation, a% t#i% %trate+* #a% not een

%#oGn to red$(e )oridit* or )ortait*.

>atient% Git# &or) a +ro$' at #i+# ri%H &or &$rt#er .

reention o& and 're($r%or e%ion% inoe% t#e

&ooGin+ )ea%$re%:

M 'rote(tion o& t#e %Hin * $%e o& a''ro'riate (ot#in+ and

%$n%(reen% d$rin+ o$tdoor a(tiitie%N

M %'endin+ a% )$(# ti)e a% 'o%%ie in t#e %#ade at )idda*

11.00 a) to 3.00')N

M Gearin+ o& road-ri))ed #at% o$tdoor%N

M aoidan(e o& %$ned%, a)'% and (ain%N

M $%e o& %$n%(reen% doe% not aoG &or in(rea%ed %$n ex'o-

%$re ti)e%.

V.2. (reenin+ and (ini(a dia+no%i%

D$e to t#e &re$en(* o& , do(tor% %#o$d e &a)iiar Git#

t#e (ini(a 're%entation% o& t#e%e t$)o$r% and %#o$d e atten-

tie to t#eir 'o%%ie on%et. Qe #ae no &i+$re% (on(ernin+ a(($-

ra(* o& dia+no%i% *


35/56

M in&or) t#e 'atient t#at t#e 're%en(e o& t#i% A indi(ate%

a ri%H o& %Hin (an(er at t#e %a)e %ite or on ot#er %Hin

area%, and t#at it i% (on%e$ent* ne(e%%ar* to exa)ine t#e

entire %Hin %$r&a(e to en%$re t#at t#ere are no &$rt#er %$%-

'e(t e%ion%N

M adi%e t#e 'atient to e attentie to t#e (ondition o& t#eir%Hin and to t#e a''earan(e o& an* neG e%ion%.

Ce(o))endation%

(reenin+ &or i% re(o))ended a&ter t#e a+e o& 0,

'arti($ar* in 'atient% at ri%H a% de&ined * t#e &ooGin+

(riteria: i+#t %Hin, #i+# ee o& %$n ex'o%$re, #eioder)a,

'reio$% #i%tor* o& %Hin (an(er, radiot#era'*, (#roni(

$(eration, od %(ar%, #idradeniti% %$''$ritia, et(. 'ro&e%%iona

(on%en%$%.

"#e %Hin (an e exa)ined at an* )edi(a (on%$tation, $t t#e

o'ti)a &re$en(* o& %$(# exa)ination i% not HnoGn.

ini(a dia+no%i% o& in(i'ient i% di&&i($t: A A%#oGin+ %i+n% o& exten%ion or 'er%i%ten(e &ooGin+ ade$ate

treat)ent %#o$d e ine%ti+ated * #i%to'at#oo+i(a

exa)ination 'ro&e%- %iona (on%en%$%.

V.3. Coe o& io'%*

A((ordin+ to t#e 5@C +$ideine%,R'rior io'%* i% $%e&$ in

(a%e% o& (ini(a* $n(ertain dia+no%i% G#ere t#e (#oi(e o&

treat- )ent )a* e +$ided * #i%too+i(a %$t*'e or de't# o&

ina%ion, and 'rior to exten%ie %$r+er* in area% o& (o%)eti(

(on(ern, to deter)ine t#e %'read o& a (ini(a* 'oor*

dei)ited t$)o$r )$ti'e io'%ie%.

(a'e or '$n(# io'%* %#o$d e 'er&or)ed to a%%e%% t$)o$rde't# 'arti($ar* e&ore radiot#era'*.


36/56

"ae 9 $))ar* o& indi(ation% &or A treat)ent

atient &ar &ro) )onitorin+

treat)ent (entre

r*ot#era'* -ara)edi(a de%irae

@edi(o-e(ono)i( (on%ideration%

o%t L e&&i(a(* ratio * $nit (o%t

r*ot#era'*, -D" a%%i&i(ation * $nit (o%t

"#i% tae %$))ariKe% t#e t#era'e$ti( o'tion% a% a &$n(tion o& di%ea%e (#ara(teri%ti(% and e%ion%.

In t#e a%en(e o& (o)'aratie %t$die% on t#e di&&erent treat)ent%, t#e (#oi(e% 'ro'o%ed eoG are a%ed on t#e %ettin+ and on

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