U M M NG TIU HA

GIST (Gastro-Intestinal Stromal Tumour)

Trng Hi PGS.TS. Ngoi khoa i hc Y Dc TP.HCM

Lch s

Trc ay a so GIST c chan oan u co nguon goc c trn hay u co nguon goc than kinh.

1983 : Mazur va Clark xac nh ro ban chat nhng u nay xuat nguon t te bao mo em ke Cajal [9], [33], [34], [37].

M ra hng iu tr mi

GIST : ot bien gen c- kit hoat ong nh men tyrosine kinase Lieu phap ngam trung ch (target therapy) thuoc c che men tyrosin kinase (Imatinib)

Tnh thi s

02/2002: FDA cua My phe chuan Imatinib trong ieu tr GIST vi CD117 (+) khong mo c hoac a co di can

05/2003:

Cong ong chung Chau Au thong qua Nhat Ban phe chuan trong ieu tr GIST [3], [10], [12],

07/2003: Imatinib [24].

Dch t hc
S ca mc thm/nm Xut / 1.000.000 dn

4.500-6.000

16-20

Php
Anh Thy in H Lan i Loan
Phn Lan

150-300
16-20 14,5 14,5 14,5 10-20

Tui v gii

Thng xay ra BN ln tuoi Trung bnh 40-60 tuoi. Tuoi <40 5-20% Tre em <1%. Trong nhom tuoi <40, nhom 10-20 tuoi thng gap nht, n > nam thng gap da day, loai thng mo khc ngi ln v khong co ot bien Kit

Tan suat mac benh cua nam = n tuy nhien, GIST ac tnh thng gap nam hn.

Thc t Vit Nam

Hien nay ky thuat hoa mo mien dch phat trien manh. Ch nh nhuom HMMD / dau an CD117 oi vi u trung mo ng tieu hoa GIST co xu hng tang. GIST bat au c e cap va nghien cu trong nhieu lnh vc t LS, CHA, GPB

Bang phan loai u trung mo ng tieu hoa theo AFIP nam 2003 [33]
U mo em ng tieu hoa: lanh va ac Nhom u c trn: lanh va ac Nhom u co nguon goc than kinh: lanh va ac Polp viem dang si Nhom u te bao m Nhom u mo bao si U c van - Sarcom c van va u dang c van U te bao noi mo mach mau/u mach mau

GIST

GIST la loai u trung mo cua ng tieu hoa chiem t le cao nhat U mo em ng tieu hoa con co cac ten khac : U te bao mo em ke cua Cajal, u te bao tao nhp Co nguon goc t te bao mo em ke Cajal, vi ac trng bieu hien qua mc thu the tyrosine kinase KIT. oi khi giong te bao c trn hoc te bao than kinh C khi u trong o bung va khong lien quan vi ng tieu hoa

Sinh bnh hc

80%-95% GIST co ot bien KIT KIT: thu the tang trng xuyen mang, san pham cua tien gen sinh ung c-kit nam tren nhiem sac the so 4. Trong s GIST khng c ot bien KIT, 35% c t bin gen PDGFRA Ngoai ra, con cac bien oi gen khac, ma quan trong nhat la mat chc nang cua cac gen e nen u nam tren nhanh dai cua nhiem sac the 14q va 22q.

T bo Cajal

1911 Santiago Ramon y Cajal ngun gc c trn tiu ha 1982 Thuneberg nguon goc than kinh. Hien nay t bo Cajal c nguon goc t trung mo co kha nang biet hoa va theo hng c, va theo hng than kinh.

T bo Cajal
rut, t bo Cajal co nhieu trong am roi than kinh Auerbach, xung quanh cac te bao hach than kinh va cho cac nhanh noi vao cac te bao c trn hoac nam trong lp c hoat ong nh mot te bao tao nhp, kch thch co bop ruot. cn ong vai tro trung gian dan truyen than kinh cua he than kinh t ong ruot

Tan suat tao nhp cua te bao Cajal

V tr Tn sut hot ng to nhp (ln/pht)

D dy T trng

3 12

Hi trng
i trng

10
3

Cac te bao mo em ke Cajal trong lp c cua ruot tha dng tnh vi CD117 (pAb A4502). Cac te bao c trn am tnh vi CD117

Cc hoi chng u mo em ng tieu hoa

Benh a u si than kinh typ 1 Tam chng Carmey

gom u mo em ng tieu hoa da day ket hp vi u te bao can hach hoac u lanh sun phoi, hoac ket hp ca hai

Hoi chng u mo em ng tieu hoa gia nh

U mo em ng tieu hoa vach da day, oi niem mac ben tren cho hnh anh giong polp
(Nguon Rosai and Ackermans Surgical Pathology 9e)

i th

U thng gap di niem mac, trong lp c hoac di thanh mac. U co gii han ro, n oc hoac nhieu thuy, tron hoac bau duc, co lp vo bao, khong lien quan vi lp c niem va c bao quanh bi lp c niem. Mot so u co khuynh hng nho vao long ruot. Niem mac tren u co the b loet. U co the pha lp c niem va lan tran ra mo ke can, oi khi khong the phan biet u t ruot xam lan ra sau phuc mac hay ngc lai.

i th

Mat o mem, b cac u ac tnh. Dien cat u khong ong nhat. Mau sac u thay oi t mau xam en nau o, co the co vung xuat huyet, hoai t, thoai hoa nang. Tren noi soi, u thng co hnh vom, hnh nam oi lp niem mac len tren, lp niem mac thng co loet sau trung tam u.

Vi th

U gom co 2 loai te bao chnh: te bao hnh thoi (70%) va dang thng mo( 30%). Phan bao trong u mo em ng tieu hoa thay oi t 0-20PB/ 50 quang trng ln va hiem khi co t le phan bao cao

U mo em ng tieu hoa co dang te bao hnh thoi xep xoay loc

(Nguon Rosai and Ackermans Surgical Pathology 9e)

U mo em ng tieu hoa co dang te bao hnh thoi xep dang hang rao
(Nguon Rosai and Ackermans Surgical Pathology 9e)

U mo em ng tieu hoa dang thng mo

(Nguon Rosai and Ackermans Surgical Pathology 9e)

HMMD: T le dng tnh cua te bao u vi cac dau an mien dch

Cac KT CD117 T le (+) 81-100%

CD34
SMA h-Caldesmon, Calponin Desmin Cytokeratins

47-100%
0-47% # 25% > 20% nho

Dau an mien dch trong chan oan u trung mo ng tieu hoa

CD117 CD34 SMA Desmin S100 GFAP

U mo em ng tieu hoa U c trn

+ -/+ -

+/-/+ -/+ -

-/+ + + -/+

-/+ + -/+ -

-/+ + -

+ -

Sarcom c trn
U vo bao than kinh Sarcom khong biet hoa

U mo em ng tieu hoa dng tnh manh vi CD117 (Nguon Rosai and Ackermans Surgical Pathology 9e)

Kch thc u, so lng phan bao va tiem nang di can cua u mo em ng tieu hoa
So lng PB/50 QTL <5 < 5 Tiem nang di can Rat thap hoac khong Thap

Kch thc u < 2 cm 2 5 cm

5 10 cm
> 10 cm

5 10
> 10

Trung bnh
Cao

Trieu chng lam sang

khong ac hieu, tuy thuoc vao kch thc, v tr cua u. co khuynh hng gay ra cac trieu chng tac nghen, chen ep. ng tieu hoa di thng gay ra tao bon, roi loan thoi quen ruot.

V tr khi u

< 5%
< 50-70%

< 5%

< 25-40% < 5%

ngoi tiu ha 6,7%

Triu chng lm sng

u nho khong co trieu chng, phat hien tnh c trong m, noi soi tieu hoa hoac XQ do mot benh khac hoac qua t thiet (1/3 trng hp) u ln au bung , XHTH ( 50%), tac ruot, oi ma, s c u bung hoac u trc trang, u v gay thung ruot, gay tac mat. 10% co di can xa tai thi iem phat hien u. ( di can gan, gieo rac o bung, hiem di can hach)

iu tr

Phau thut chu yeu neu u cha lan rong lay i toan bo khoi u. nu u a lan rong sang cac c quan khac cung co gang lay u

khong can phai nao hach

Ha tr X tr

t p ng gim triu chng au

ieu tr nham trung ch

2001 - Imatinib mesylate (Gleevec) ieu tr GIST co CD117 (+) khong mo c hoac a di can. Thuoc tan cong vao protein kit hay protein PDGFRA c che te bao phat trien va phan chia. Tac dung phu t: ay bung, tang nhu ong ruot, phu quanh mat. Hiu qu:
59% BN khoi u giam ang ke. 15% BN cam thay kho chu do co bien oi trong viec ot bien gen ckit.

Nhc iem: at tien.

ieu tr u mo em ng tieu hoa di can

Phau thuat lay u gan di can Pha huy khoi u di can gan /CT, SA.
Phau thuat ong lanh (cryosurgery) RFA TACE Bm alcohol.

Tin lng

Tien lng phu thuoc vao v tr, kch thc u, ch so phan bao, tuoi benh nhan. Thi gian song phu thuoc vao v tr u: tien lng tot theo th t thc quan, da day va ruot gia, ruot non.

Tin lng
Sng them 5 nm
sau mo lay het u 34% 10%

Thi gian song trung bnh

46 th 21 th

khong lay het u