UNG TH GAN NGUYN PHT

Mc tiu

1. K c cc yu t bnh nguyn v yu t nguy c ca ung th gan nguyn pht.

2. Trnh by c cc triu chng lm sng v cn lm sng ca ung th gan nguyn pht.

3. K c cc phng php iu tr ngoi khoa v khng phi ngoi khoa ca ung th gan nguyn pht 4. Trnh by c ch nh, c ch v nguyn tc iu tr ung th gan nguyn pht bng cch tim cn tuyt i v gy tc mch bng ha cht Ni dung

I. I CNG ng hng th 4 trong cc loi ung th trn th gii.

Trung quc, ng nam : ng hng u nam gii.

Min Bc VN: ng th 3 trong cc loi ung th.

TP H Ch Minh: ng th 1 nam v th 5 n. ng nam : c tn sut cao, lin quan nhim virus vim gan B.

Tin lng xu, t l sng st sau 5 nm di 3%. Cc th t chc hc thng gp l:

Ung th biu m t bo gan (Hepato-cellular Carcinoma) Ung th biu m ng mt (Cholangio-cellular Carcinoma).

Cc loi khc: Ung th nguyn bo gan, Angiosarcome

II. BNH NGUYN V YU T NGUY C 1. Virus vim gan B

Tn sut UTG ngi HBsAg (+) > 200 ln so vi ngi HBsAg(-). Tn sut HBsAg UTG > 6-20 ln dn s ni chung (Chu : 60-80%).

Protein X trn genome virus B c l c vai tr trong t bin gy ung th. Vng dch t nhim virus vim gan B cao th cng c tn sut ung th gan cao.

Gy ung th gan qua 2 c ch: trc tip v gin tip qua trung gian x gan

2. Virus vim gan C Cc nghin cu v sinh hc phn t, s dng RT-PCR, cho php pht hin ARN ca virus C trong 50-70% huyt thanh v trong 55-100% t chc gan nhng bnh nhn UTBMTBG v khng c HBsAg.

90% ung th gan lin quan vi virus C xut hin trn mt nn gan x Nhng bnh nhn ung th gan c Anti-HCV dng tnh (c hoc khng c HBsAg) thng c cc thng tn gan nng hn (70% x gan, trong 60-70% thuc Child B hoc C) so vi nhng bnh nhn ch c HBsAg dng tnh (50% x gan, trong 65% thuc Child A) v gan thng c nhiu khi u hn

3. X gan: do bt k nguyn nhn no. 4. Aflatoxin B1: c t nm mc (Aspergillus), thng gp trong u phng mc; c chng minh l cht gy ung th gan chut, gia cm Vai tr sinh ung th c l qua trung gian cht chuyn ha l Epoxide gn vo cc acid nucleic v thay i s sao m ADN.

Tng tc vi protein 53 t bin. 5. Cc yu t khc

5.1. Ru: c l thc y qu trnh sinh ung th

5.2. Ni tit t nam Androgen, thuc nga thai ung. 5.3. Ha cht (Thorotrast),

5.4. K sinh trng (Schistosoma japonicum, Sch. mansoni, clonorchis sinensis) 5.5. Thiu alpha 1-antitrypsin, thng gp cc kiu hnh ZZ v MZ.

5.6. Nhim huyt thit t (Hmechromatose), H/c Budd-Chiari. III.TRIU CHNG

1. Triu chng c nng v ton thn

1.1. au bng: thng gp, cm gic nng tc h sn phi, lan sau lng, him khi au d di.

1.2. Ri lon tiu ha: chn n, bun nn, nn, i chy. 1.3. St: lin tc, dao ng.

1.4. Gy st r giai on mun. 2. Triu chng thc th

2.1. Gan ln: nhn thy hoc s thy di b sn phi, cng, b mt khng u, au nhiu hoc t, c khi c nh khng di ng theo nhp th. C khi gan ln vt qu ng gia.

2.2. Vng da: ch yu do chn p ng mt trong gan. 2.3. Bng: t hoc nhiu, c th gp bng mu, ti to nhanh sau chc tho.

2.4. Nghe: ting thi trn vng gan 3. Sinh hc

3.1. Cng thc mu: thiu mu, c bit c khi c a hng cu.

3.2. Tc lng mu tng tng 3.3. Chc nng gan: ch ri lon trong ung th gan trn nn x gan hoc khi khi U chim trn 75% th tch gan. Enzyme gan: Phosphatase kim, gamma GT, 5 Nuclotidase, Alpha-2 Globulin, SGOT thng cao hn SGPT. 3.4. Cc cht ch im ung th

3.4.1. Alpha Foeto Protein (AFP)

L mt Glycoprotein do gan phi sn xut, gim 3 tun sau sinh, nng ngi trng thnh khong 4-10 ng/ml. khi AFP > 1000ng/ml: hu nh chc chn ung th gan nguyn pht.

Tng nh trong u qui bung trn g, tinh hon, mt s ung th tiu ha, vim gan hoi t

AFP c i lc Lectin (AFP - L3) mi c tm ra, c hiu hn AFP nhng k thut xt nghim phc tp.

Nu khng c iu kin nh lng, c th nh tnh AFP bng phng php min dch khuch tn (Ouchterlony). 3.4.2. DCP (Descarboxy Prothrombin hay PIVKA-II) dng tnh 70% bnh nhn ung th gan nguyn pht v khong 50% nhng bnh nhn ung th gan c AFP bnh thng.

3.4.3. Alpha L-Fucosidase: enzyme ny tng cao trong ung th gan nguyn pht, vi c hiu 90% v nhy khong 75%, cng tng trong u gan lnh tnh.

4. Thm d hnh nh

4.1.Siu m Mt hoc nhiu khi (nodule) trong gan.

Echo giu, ngho, hn hp, dng khm

X y mch mu, ng mt (bending sign), vin gim m chung quanh Tng sinh mch mu trong u, thng c huyt khi trong tnh mch ca.

4.2. Chp ct lp t trng: mt /nhiu khi gim mt (hypodense), bt thuc khng u, gip hng dn chc ht, sinh thit.

4.3. Chp ng mch Xt nghim c bn tin phu, gip xc nh v tr, ti mu, kh nng ct b u qua trung gian mt Catheter lun vo vo ng mch thn tng

Hnh nh bi tng sinh mch mu (th ng mch) Ti mu t chc ln xn, h mch mu (th nhu m)

lung mu tnh mch v sm (th tnh mch) 5. Gii phu bnh

5.1. Sinh thit: sinh thit di s hng dn ca siu m, CT scan hoc soi bng Sinh thit: chnh xc nhng d chy mu.

5.2. Chc ht kim nh: t bin chng, nhng chnh xc v nhy thp hn sinh thit.

IV. CC HI CHNG CN UNG TH 1. H ng mu: do t bo u tit yu t c hot tnh tng t Insulin. 2. Tng Calci mu: do u tit yu t ging hormon cn gip.

3. a hng cu: do u tit yu t tng t Erythropoietine 4. Yu t V bnh thng nghch l

V. TIN TRIN & BIN CHNG 1. Tin trin: thng l nng, tin lng xu, t vong 6-12 thng

2. Cc bin chng:

2.1.Bng ung th: 2.2.Vng da: chn p ng mt trong gan

2.3.Xut huyt - Xut huyt tiu ha cao: huyt khi ca

- Phc mc: v nhn ung th 2.4.Chn p tnh mch trn gan hoc tnh mch ch di

2.5.Di cn: trong gan, phi, mng phi, xng, hch, no.

VI. CHN ON PHN BIT 1. Gan au km st

1.1. p xe gan

1.2. Sn l gan: yu t dch t + tng bch cu i toan + huyt thanh chn on

2. Vng da

2.1. Do u chn p: Gan v ti mt ln, phn bit nh siu m. 2.2. Vim gan: giai on tin vng da, SGPT tng rt cao, cc ch im huyt thanh ca virus vim gan v thm d hnh nh.

3. U h sn phi 3.1. Vim gan mn

3.2. Kn gan, Adenome, lymphosarcome, 3.3. K gan th pht: Tm ung th nguyn pht, Alpha FP bnh thng, t chc hc

VII. IU TR 1. iu tr ngoi khoa

1.1. Phu thut ct b khi u

Phu thut ct gan vn l phng php iu tr trit nht i vi ung th gan nguyn pht. * Ch nh Thng ch nh phu thut c p dng cho cc bnh nhn ung th gan giai on I, II v IIIA. - Mt s tiu chun thng c xt trong ch nh ct gan

+ Kch thc di 5 cm + Mt thu

+ Khi u c v

* Chng ch nh phu thut -Chc nng gan km do x gan

-Khi u xm ln c hai thy gan -Khi u xm ln hoc lm tc ng gan chung

-Khi u xm ln tnh mch ch di -Huyt khi tnh mch ca

-Xm ln hch lympho

-Di cn xa (thng gp l phi v xng)

Ngay sau phu thut, s ti pht khi u l c th xy ra, c khi cn ct b ln 2 hoc thm ch ln 3. Khong cch an ton cn c ti thiu l 1 cm cch t chc u.

Vit Nam, GS Tn tht Tng thc hin t nhng nm 70, phu thut nhng u nh n c, sau nng min dch bng LH1 cho kt qu tt. K thut n y thng p dng cho u n c c kch thc di 5cm, tui di 70. Chc nng gan cn li l yu t chnh quyt nh tin lng, thng ct theo thy hoc phn thy.

Nht, t vong sau m l 3 - 11%, sng trn 3 nm l 46%. Kt qu tt nht khi u di 2cm, t l sng trn 5 nm l 60, 5%.

Php, Bismuth thc hin 35 trng hp t 1970-1984 t l sng trn 2 nm l 32%. Thi gian sng cn ty thuc vo ch s Child-Pudg trn 3 nm l 51% cho Child A, 12% cho B v C. Bin chng: Cc bin chng thng gp sau m ct gan l chy mu, nhim khun, bng v suy gan. Him hn l d ng mt.

1.2. Ghp gan Li ch chnh ca phng php ny l loi b tt c phn ung th v cc tn thng trc n, loi b nguy c do tng p lc ca, vn cn nguy c ti pht

vim gan trn gan ghp. Kt qu Hannover cho thy thi gian sng trn 3 nm l 15%, Pittsburgh vi u nh n c th sng trn 5 nm l 45%. Cc trng hp ch c mt u di 5 cm hoc c di 3 u nh hn 3 cm th tin lng sau ghp rt tt, gn ging nh cc bnh nhn ghp tng khc do cc l do khng phi ung th.

2. iu tr khng ngoi khoa 2.1.Tim cn tuyt i qua da trc tip vo khi u di s hng dn ca siu m

Nm 1982, ln u tin Nht bn, cc tc gi Ebara M v Okuda K... nghin cu phng php iu tr UTBMTBG bng phng php tim Ethanol vo khi u gan v thu c kt qu kh quan. Sau c nhiu nghin cu Php, , Trung Quc...vi cc kt qu tt. * C ch: Ethanol gy ra huyt khi ng mch trong u, t gy ra mt s hoi t ng khi u v tnh trng thiu mu cc b khi u. * Ch nh

Cc bnh nhn c chn on xc nh l UTBMTBG

S lng khi u khng qu 3 khi, tt c u l u c v bc

Kch thc u thng nh di 5 cm, thc t kch thc tu thuc s lng

khi u (1 u 12 cm, 2 u 6 cm, 3 u 4 cm). Phn Child-Pugh A v B; T Prothrombin trn 60%.

* Phng php Phng tin, dng c:

K thut tim ethanol c thc hin di s hng dn ca siu m hoc

CT Scan.

Kim tim Chiba hoc Terumo: 0, 7-0, 9 X 7-15 cm.

Ethanol tuyt i: 99, 8 %, ng ng 5 cc. Lidocain 1%, thuc gim au, dng c st trng.

* K thut Xc nh khi u gan cn chc di siu m hoc CT Scan

Xc nh v tr chc kim, gy t Chc kim qua da vo trung tm khi u di s hng dn ca siu m hoc

CT scan

Tim chm Ethanol vo khi u, va tim va quan st s khuch tn Ethanol

ti ch Rt kim ra st v gan, thay ng tim c lidocain gy t v gan

Rt kim, bng ti ch. Liu lng: 1-2 v tr tim/mt ln x 2 ln mi tun; Mi ln tim 2-12 cc.

Tng liu Ethanol phi tim c tnh theo cng thc Sugiura N (Nht Bn) 1983 V = 4/3 (r + 0.5)3.

Trong : V l tng liu Ethanol

R: bn knh khi u Kt qu s b ca mt s nghin cu: theo nhiu nghin cu ca nhiu tc gi ngoi nc (Livraghi, Ebara...) v trong nc (Mai Hng Bng) th kt qu rt kh quan, t l sng thm sau 3 nm l 71% (Child A), v 41% (Child B), mt s bnh nhn sng trn 7 nm. Phn ln bnh nhn ci thin tt v lm sng, AFP gim r, t l khi u hoi t hon ton trn siu m l hn 60%. K thut ny cn c th gip iu tr cm mu trong trng hp v khi ung th gan.

2.2. Phng php gy tc mch

Phng php gy tc mch c s dng ln u tin vo nm 1975 ti M. Nakamura iu tr gy tc mch cho 200 bnh nhn ung th gan nguyn pht v cho t l sng thm 2 thng, 12 thng v 24 thng tng ng l 71%, 48, 1% v 20, 8%. Nhm gy tc mch c phi hp vi lipiodol c thi gian sng thm di hn c ngha

* C ch Bnh thng, gan nhn 2 ngun mu cung cp l ng mch gan v tnh mch ca, trong cc khi u nhn mu ch yu t ng mch gan, do vic gy tc mch bng cch tim vo nhnh ng mch chn lc nui dng khi u s gp phn gy hoi t khi u nhng khng gin on s ti mu i vi gan lnh. Vic phi hp tc dng gy thiu mu hoi t vi tc dng ca cc ha cht chng ung th s lm tng tc dng iu tr.

* Cc k thut gy tc mch + Bt tt ng mch gan chn lc bng mnh bt b gelatin, a vo nhnh ng mch nui dng u thng qua ng mch i v ng mch thn tng.

+ Bt tc ng mch gan siu chn lc + Bt tc ng mch gan kt hp tim ha cht chng u (TACE), cc ho cht thng dng l doxorubicine, cisplatin...

+ Bt tc ng mch gan bng ha du (TOCE)

Tc dng ph sau bt tt l: st, au bng, nn, bng, hn m gan, tng transaminase.

Ngoi ra c th gy bin chng tt mch ngoi gan hoc gy p xe ha. Cc k thut ny c th lp li sau mt khong thi gian t 3-6 thng.

* Ch nh + Cc khi u gan khng phu thut ct b c

+ iu tr cp cu xut huyt phc mc do v khi u gan

+ Gy tc mch trc m lm gim bt kch thc khi u v tng thi gian sng thm sau m.

+ Trong mi trng hp, tnh mch ca khng c c huyt khi 2.3. Cc iu tr tm thi khc

* Phng x tr liu Trc y iu tr phng x ngo i cho bnh nhn ung th gan nguyn pht c s dng. Nhng do kt qu hn ch nn hin nay t c ch nh. Nhng cht phng x c s dng l I131-antiferritin, khng th n cln gn I 131-anti

HCC. Hin nay chu u cng c nghin cu iu tr tia x chn lc vo khi u vi kt qu ban du c ko di hi gian sng thm ca bnh nhn. * Ha tr liu

Cc ha cht thng c s dng l 5 FU, cisplatin, doxorubicin, Mitomycine C...

ng s dng phong ph: ung, tim tnh mch, tim vo dy chng trn, tnh mch ca...

* Min dch tr liu

Cc phng tin min dch thng c s dng l phng tin c ngun gc vi sinh vt (BCG, corynebacterrium, ..), ha cht (levamizole, Isoprinosin...) hoc nhm Cytokin (IL2, IFN-beta, IFN-gamma...). Tuy nhin khng c phng php no hon ton c hiu.

Mt s tc gi ngh tim BCG di v gan sau khi ct b khi u vi hy vng tng min dch khng c hiu. Lai v cng s s dng phi hp Doxorubicine + IFN-alpha 2 cho thy c gim kch hc u, gim cc bin chng so vi nhm chng. K thut chuyn gen: a cc gen tr liu c hiu n tiu dit cc t bo c tnh nhng khng lm thng tn t chc gan lnh. Cc vect virus nh adenovirus

thng c s dng. Cc khng th n dng phn ng vi khi u cng dc s dng phn b cc gen n cc t bo ung th.

* Tamoxifene

S ph thuc kch dc t v s hin din ca th th ni tit trong ung th gan, gi cho s pht trin ca u l do kch thch t, tuy nhin nghin cu s b vi Tamoxifen cho kt qu cn tranh ci. * Nhit tr liu

Thng dng sng cao tn (radio frequence ablation:RFA) pht ra nhit nng thng qua mt cy kim cm sn trong lng khi u, nhit cao s gip tiu hu t bo ung th. Kt qu bc u kh tt.

VIII. KT LUN Ung th gan nguyn pht kh ph bin nc ta, triu chng a dng v thng khi pht m thm, chn on phn ln giai on mun nn iu tr kh khn, tin lng thng rt xu.

D phng ung th gan ch yu da vo tim chng phng virus vim gan B v iu tr cc bnh vim gan mn do virus.