A NOVEL TREATM ENT FOR HEPATIC HYDXTID CYSTSCOM BINATION THERAPY OF PM ZIQUANTEL ORM ETH O TR EX ATE W ITH A LBEN DA ZO LE .

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I!!ik -'i.;tJ-'. Al Iollillj.:l to lilll.l it tll-tlg tllklt lligllt ellllallce tllt: iîctioll ol- kllbellkl' azole or be al1 alternative il1 treatlllttllt ofllellitt ic I kytlcltid cysts il) l11;k: p.. tlte ttl-fkcts ot- 1... - aziqtlalllel 0,. l'lletllolrexatc alolle or in colllbillatiol) Mvitllktlbtlltkfklzk) le Nvel'e lklslctl . -I-lt ' t'ty-ttigldl kttltl It j);) z'ellts svitll llytlêltid cysts of tlle l iver colllplettzd tlpe sitldyklj-lttl' llc-illg sejl:ll'ltf t.'t1 1':I;)t!. !' lljy ilhli) 6 ll'ekjl 'tlktJlt gl'otllls receivillg itlbelldazole oI- prazitjualltel orlllel llïtpël'k...xtlte u1' tllc iI' ctllkll-lil'ii, l i()I). l'ttsjlccti vcly. 11 tsîlily doses lk)l' 4 xvettks. zï.t tlle elld of lrcallllelll, tll'ugse ll-ttc î s h.h'kll't! t-tvil l tlitl es $ 1'12$, :

INTRODU CTION tlttty al'e ciltlstld b' y illjttction

PAT IENTS ''l-lle writtenGellerkll ! lospitala t Nass i riyah C i ty ;.. @I' .gr.'' ''(j:)p'r , MR THOE S

J . F ac' , I3agl )tl ad :. ()t)0, Vt) l .-1 2, N t? . 3

l l ïtt gcrlllillal lkkJ c 1' t:kl tisckl 1..,,), c()1 l 11 ) i ! lcd tl lel'tîl ')y f.j t' tl 11,y 2 t) 1- t l lcsc tlrtlgs ïvas grcatcr 11:a11 tllktt l'lrotltlced byI 11 (.) l1t) t llerapy . ( I ''' l 'ktjt tlgrkt 1) I1s l t t.t 7 ) .It sllould be staletl 111:1! l'llally ()1* llltt lllodktl'llttl- kizt!tl (...1- slllall cysts sllrinkttd nlalkedlys alld sonletilnescolupletely, whicl) precltlded s' lrgery. Large cysts lnore tllall 8cln in dialueter, cspecially those w, ithdaugllter cysts, ditl llot slloNv a good rcgressiol) il) a large 'llroportion of thenl. (F ig. I ). Cysts outside theliver. as in oluellttlll), k idlley o!- spleell. sllrillktttl lkltll-e lllall llçpat ic cysts. (-I-able2).

' ' . wl-jkcts Nvere illsigili licallt cl illical ly atld trallsiellt -l-lley Nvere luostly gastrointestitlal QccurringI ) l t l x.,.,. . s l d t. t,

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in 9 patients for tlle first lebv days of- treatlnellt. , . .t .4 patient had lleadaclle alld dl-oTvsi lless fbr tlle lirst 2 days o f' trktatnlellt il1 praziqualltel or praziquantel andalbenklazole grotlp .011e patitlllt il1 albendazulc grotlp' llktd î11 ild elevation of- SCPT' that .reversed at cnd oftreatlnent .Ol1e pkttiellt il1 llletlllltl-exate-ttlbclldflzole grutlp hatl mild letlcopcn ia that reversçd after

j . ' ' . ' . . .- * ,colllplet l1g tlle tl ttittlllellt.ltable 3 ) ' . , , .

13 . 17 ro ') yl; l c t i c s t t l dy. :Tlle use of dil-ikrellt dl'tlg tl-eatnlttllts fbr one nlolltll folloNvillg llydatid surgery prevented tlle forn'lation ofneyv cysts in liver or pdl-itolltlulll or elsesvhere Nvllen paticllts vvere exalnilletl çlinically and by abdoluinalultrasound 6 nlontlls aj-ter stlrgery. Tlle only esceptioll was tlle recurrence of a single cyst locally at the

- - i i 1 t)lle I)klt ittltf, o 1* :1 l belldazol t.t llltsllolllelnyjy' group (table 4). S ide t! l-fects Nvere ln i rlor ands i te o f opcl at ol1 I- i

ll'llllsittllt. No clllïllge iJl livttr 1 Slllctiol) oI- blood illdices qvlîs sttttl).

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l 1) t)tll- prttset) t .$v() I'lx . e l 1 etlt i vcrless o 1- plntzitltltlllte l or llltttlltltrexate lllollotllet-apy t)l) llydatid cysts i 1-1 nlanilltl icllttlst llklt tllkr ir l i l)i ti so l tlb i i i t y ellotlgl) ttè pltss auross tlle cyst Nva l l itlto tlle llydatid tlu id tlltlstlk: l 'k l

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ts nloretllall :1 lbe lldazo 1e& btlt llliltilctrexate 'svas i 11 lbriot' to botll. l losvever, tlle usc o f nletllotrexate Nvith eitherdrtlg I'lrod tlced potellt iat i()l'1 tr()1'13. pared to rttspect i vtz lllfnnotllerapy.1).1 ut tlle Lcst e I'tkct Tvas obtptil'led '$v i t i'l c(.)l'1ll) i llatitln o 1- prazitluallte l antl albendazoltl. Clur present vvork istlltt slltlyv albelltfazfr-) Ic by praziqtla kltt.'t l or l'ncthotl-cxate. svitl) (lle fornlcrcoll'l b i llat i o 1) )) rt, :t tl c i l)g-1*11 i s llal-as i t ic Jktlllktgtl tly tl ï'lsc drtlgs yvkts I'e lltrcted i 11 l'ed tlet itlll () 1- cyst size ol'! tl I ! l'asotllltl tlxal'll i natioll,retltzcting the danlage to tlle pltlx-asite gernlillal lllelubralle and by loss of protoscöl ices viabi l ity il) l'lydatidtltl id sanlples, f aken jlrior to F, tlrgical relnoval of large cysts. The scolicidal action of tllese drugs in vitrois rttported, but took sttvera! Clays to occur, tllus nlak ing tlleln ullsuitable scolicidal agents tbr stlrgcry of-

( tl l Q ) ' h ,.Ilytltttid cysts ' i'1 collljlkll isoll to tlle rklpitkly act i l'lg scolicidal clleluicals sucll as l'orlllitlin, etllanol.Ilyptlrtoltic sal ille alltl cetl-îl'hlide t 'S' 19) 'I-I1e dalniigillg el-lkct of praziquantel or albendazole nligllt bc dueto lllctir e I-lkct t)l1 I lyktlly v i tk. l jlrtlcesses stlcll l1s k 11.11.1:1 i 1.1) Iellt (1 1- tlnlllsport o f nutrie Ilts espttc ia l ly glucosc by

(7j . . (a())1.1 lbclldazo le ol to i llcl ttklscd ca lc itlll) ioll i 11 t'ltlx by praziquantc l illto tllc gerllli llal laydr orprotoscolices. Tllis is il1 addition to their inh ibitory act ion on ATP f'ornlation as a source of energy for the

- i l layer allt.l protoseolices $21-22)gel n) l1a .

Metllotrexate, Ilowever. nlay act by inhibitillg tlle forlnation ot- DNA by its dillydrofolate reductaseillllibitory actitll). tlytss illlïFbit ilpg l'llitosis allt.l gl-ovvtlt 01- gerlllillal layer and protoscolices-, tlle

l t iol) o1* illtrkkctllltllktl' ptllygltltktltllttes bj? tllis drttg also colltribtltes to its cytotosic action (231 Theîl C C tlll 1 tl 11 .llttjlatic fiblxlsis ckttlscd by Ihletllotrexate is klltl',spll il1 11,!1111 but tllis librotic ruactioll seelns to be enhancedby 1 l)e dl-ug-intltlcu.d tlegcneration of lllc llarat ile. In tlle presellt work snlall alld Illoderate' -, siwpd cystssltovved renlktrkable responss), Nvitll solne of the ;)1 shrink ing colllpletely as seen on ultrasonography whiletlle retltlctitlll ily cyst size v/as lttss Nvitll largel- uysts. partictllarly tllostt svitl) daughter cysts, as seen Nvhenstll'gery Nvkls dolle .' l t llligllt 1' kl tllal tllktse large f-'./st reqtlire longer period of treatnlellt Ol- repeated Cotlrseso f ll-ttlttlllktllt. llalvtictl l:1l'Iy ïviti' nletilotrexate oI' a ' beltdazole Inollotllerapy or their conlbined treatiuent.I Iolxtlvei- Ngitll I'Jl'klzitlt.lalltel or its conlbillatioll it seelns that tllese large cysts are unl ikely to'grow furtllerdtlc to coinlllete ltlss t)l- Ill'tv'--osccolices alld due to lllarkcd daluagc to gerlnillal layer Svitll nlonentlclearil) llklllllnatory cel l il) filtlutitkn. lt Ilas been st3ggested tllat al1 illllalllnlatory al'tt.l inlnlulle reaction is

- - i 1- tlp..: paras i te by prazi:luante I tllerapy $:-1)essc 11 t i q l (

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kt t k) 11 o .-I'1te greatcr slll.illkttge oI- eh: Jrallepatic cysts. as colnpared to cysts il1 liver, lnay be attribuled to tllinnercyst u/al I f!) tllcslz orgalls (it '. conlpared to flle tplick. advelltitia ofllepatfc cysts) alloqving greater alnotlntsof tll'tl-tjs t() I'eacll tlle llyd. l .1 . 111.1 id o (- tlles.a. 'Jysts, tllus exertillg greater anti- parasitic action. It isI-ulllétrkablc ik'l ottl' svlll-k tllat u t?(l,1 witll colllbi:letl tllerapy, lcak of- hydat id fluid 11-01,1 dalnaged cysts was

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-l-able 4 : ltate ef reci. f rellce or llydatid cyst: afler siz 1,,1/14111.$ inIlalicnîs lreated Iposlc ). erativcly b)' six prophyfaclic lreatlllcnt: for

ypne loçllltll .

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Gx l - A lbttldtl :lztlle 2 Nlild trallsient abdolnillal pain .

-' '''* 4. !. 'N = 6 . ( l luale , I fenlJlle) &vltl, llausea or diarrhea for t' f

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2. . . . k: J,' . I (l1Iale) . N1lltl E levatlon In SG PT and , .j'.

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è rt.norlnal at end of treatnlent. .' ïk'.. . . li f ': '

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Figure 1 : Histology of hepatic hydatid cyst of untreated patient

showed tbe normal structure of the cyst (H & E stain X 400) .

Figure 2 : Histology of hepatic hydatid cyst in patient treated

with albendazol 400 mg x 2/day for one month , showeddegeration of germinal layer ( EX ) , vaculation ( EEX )

and calcification (*) ( H & E stain x 400 )

Figure 4 : Histology of hepatic hydatid cyst in patient treated with

albendazole 400 mg x2 and praziquantel 600 mg x 3 for one month

howed degeneration of germinal Iayer ( EX ) vaculation andAShigh cellular infilteration ( EX ) ( H & E stain x 400 ) .

Figure 6 : Histology of hepatic hydatid cyst in patient treated

with methotrexate 2.5 mg/day and albendazole 400 mg x 2/day

Figure 5 : Histology of hepatic hydatid cyst in patient treated

with methotrexate 2.5 mg/day for one month showedion of germinal Iayer ( EX ) vaculation and fibrosisdegenerat

f the cyst ( ::::h )O ( H &E stain x 400 ) .

Figure 3 : Histology of hepatic hydatid cyst in patient treated

with praziquantel 600 mg x 3/day for one month , showedd flattening of germinal Iayer ( EEY ) , cellulardestruction an

infliteration ( ZX ) and vaculation of the cyst tissue (*) (H &E stain x 400 ) .

Figure 7 : Histology of hepatid cyst in patient treated with.- am k w*...-..a+ .. o r .- .. IA ..... ..k .- mI .a. ..a -:.. . . .- -+..1 r nn ..... .. *, '.> #