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Tap chi GAN MAT VIBT NAM so 16&17-2011 147

Nghien cmi mo benh hoc va hoa mo mien dich ung thu bieu mo tui mat

Histopathology and Immunohistochemistry of the gallbladder carcinoma

TRAN VAN HOP*, HA THI THU HIEN**

Summary

Background: In our daily work, we have found that almost all patients with the gall-

bladder carcinomas came to the medical serv- ices in the late stage. In order to be better treated for the patients we have to have the detailed prognosis and the histopathological typing, grade and the expansion level of the tumor play an important role to assess the dis- ease. Objectives: to study the histopathologi- cal typing, grade and the expansion level of the gallbladder carcinoma. Materials and Meth- ods: 111 patients operated with the gallbalad- der diseases and diagnosed definitely as carcinomas by histopathology. We have applied the WHO-2000 classification to study the histopathological typing, grade and the infiltration of the tumor to the gallbladder wall, liver and lymph node metastasis. The cases difficult to diagnose and classify the type by HE, we then have used the immunohisto- chemistry staining. Results: Histopathologi- cally, the most frequent type is

adenocarcinoma accounting for 63.1%, then the papillary type 16.2%, the others are rare.

The histopathological grading, we'have found that the dominant grades are moderate and well differentiation, 55.9% and 36.9% respec- tively. Among the 9 difficult cases to classify by HE, after the IHC, 2 cases classified as small cell carcinoma, 1 case as clear cell carcinoma, 6 cases as poor differentiated carcinoma.

The stage level: the late stage with T2, T3 are high, accounting for 74.7%. The propor- tion infiltration of the lymphatic and hematic vessel 59.5%, nerve 26.1%, liver 22.5% and lymph node metastasis 19.8%.

Conclusions: The most frequent type of the gallbladder carcinoma is adenocarcinoma and the moderate and well differentiation are dom- inant. The proportion infiltration of the lym- phatic and hematic vessel, liver and lymph

node metastasis related to the tumor stage and the histopathological grade.

Tdm t5t:

M& ddu: ung thu bilu md hii mat thudng dugc chin doin mugn v i cd tien lugng xau.

Trong dinh gii tien lugng thi tip md hgc, dg md hgc v i do xim lin cua md u li nhiing ylu to quan trgng. M«c tieu: xic djnh cic tip md hpc, do md hgc va muc dg xam lin ciia ung thu bilu md tiii mat. Ddi upmg vd phuong phdp nghiin curu-.ddi tupmg - 111 benh nhan cd bpnh ly hii mat dugc phlu thuat pit tiii m|t, md benh hgc xic djnh l i ung thu bilu md; phuong

phdp - tiln hinh phin loai md hgc, do md md hgc theo phin loai cua WHO-2000 vi xic djnh miic dg xam lin cua md u vio thinh tiii mat, xim lin gan, di cin bach. Nhimg trudng hgp khd dinh tip bing phuang phip nhudm H.E se dugc nhugm hda md miln djch. Kit qud nghiin cum: Vl tip md hgc- ung thu bilu md hiyin chilm ti le cao nhit- 63,1%, sau dd l i ung thu tuyln nhii-16,2%, cic tip khic it gap.

Md u chu ylu cd do biet hda vua v i cao

* Dai hoc Y Hi Npi, ** Benh vien Hihi Nghj Viet - Diic

(2)

148 Tap chi GAN MAT VI$T NAM so 16& 17-2011

(55,9% vi 36,9%). Cd 9 hirdng hgp khd djnh tip, hda md mien djch da xic djnh 2 trudng hgp li ung thu bilu md tl bio nhd, 1 li ung thu bilu md tl bio sing, 6 li ung thu bilu md tuyln kem bipt hda.Vl dg xam lin, u d giai doan mugn f2, T3 chilm ti 1? cao (74,7%), xim nhap mach miu, mach bach huylt - 59,5%, xam nhap thin kinh- 26,1%, gan - 22,5%, di

cin h^ch- 19,8%. Xam nhap mach miu, mach b^cb huylt, gan vi di cin bach cd lien quan tdi dd xim lin vi dO md hgc cua u. Kit lugn: ung thu bilu md tiii mat chii ylu li tip tuyln, dp bipt hda viia vi cao. Ti Ip xam nhap mach miu- m^ch b^ch huylt, thin kinh, gan vi di cin hach cd lien quan din muc dg xam lin vi dg md hpc

ciiau.

\. Dat van de

Ung thu bilu md tiii mat li u ic tinh phit trien tir niem mac tiii mat, ti le mic bpnh cd sy khic bipt giiia cic khu vyc tren the gidi th|m chi giiia cic vung trong mgt quoc gia.(5 cic nude My La tinh nhu Chile, Mexico,Bolivia cd ti Ip mic bpnh cao 5,1/100000 doi vdi nam vi 21,1/100000 ddi vdi nir. 6 nude My ung thu tiii mat chilm 0,17% cic loai ung thu doi vdi nam vi 0,49% ddi vdi nir. CJ Phip theo thong ke ciia Hdi Ngoai khoa ung thu tiii m|t chiem 2,16% cic phiu thu|t ve dudng mat, ti le nam/

nir Ii 3/5. CJ Viet Nam ung thu tui m|t li bpnh

* r y

khdng phd bien, nhung cac nghien ciiu gin diy cho thay benh cd xu hudng ngiy cing tang vi phan ldn cd kit hgp vdi sdi tiii mat (3,4).

Cic nghien ciiu deu nh|n thiy benh gap d nu

nhilu ban nam tii 3 den 5 lan vi d ngudi cao tuoi chilm ti le cao( 1,2,10, 11). Ngiy nay nhd cd cic phuomg ti^n hipn dai trong chin doin hinh inh da gdp phin phit hien nhilu trudng hgp bpnh, trong dd cd nhiing u cdn nhd. Tuy nhien ung thu tiii m|t vin li bpnh cd tiln triln ning nl vi tien lugng xiu. Cd nhilu ylu td inh hudng tdi thdi gian sdng them sau phlu thu|t ciia ngudi bpnh, trong dd cd tip md hgc, dg md hgc vi sy xim lin ciia md u. Nghien ciiu vl phin loai tip md, do md hgc vi dinh

f ' r X X

gii sy xim lan ciia md u ludn li van de cin thilt, nhung nhihig nghien cuu niy d nude ta cdn it. Muc tieu nghien cihi: tim hiiu mpt so dgc mo hpc,hda mo mien dich vd suxdm ldn cda ung thu bieu mo tdi mgt ".

n . Doi tugng v^ phuong ph^p nghien cihi

r

2.1 Doi tupmg nghiin ciru

Nhiing bpnh nhan cd benh ly tiii mat cd chi djnh phlu thu|t cit toin bg hii m|t vi dugc md bpnh hgc chin doin xic dinh li ung thu bieu md hii m|t. Trong thdi gian tii nam 2002 den 2009 cd 113 trudng hgp dim bio yeu ciu tren dugc dua vio nghien ciiu.

2.2 Phuong phdp nghiin cdm.

Tat ci cic hii m|t sau phau thu|t dugc cit 3 minh, trong dd 1 minh liy vio viing xam lin sau nhat cua md u, 2 minh liy d viing ranh gidi md u vi md linh.Cic bach nao vet trong phlu thuat, phin nhu md gan cd xam nh|p md u diu

dugc cat minh lim xet nghipm md bpnh hgc Cic minh dugc co dinh trong formol 10%, chuyin vui nIn, cit minh diy 4|j., nhugm H.E.

Cic tieu bin dugc dgc dudi kinh hiln vi quang hgc d cic do phdng dai 100, 200 vi 400 lan.Nhihig hudng hgp tren H.E khd khin hong djnh tip md bpnh hgc dugc nhugm hda md mien djch theo phuang phap phii mgt Idp vdi cac diu in cda hang Dako.

Phan loai md bpnh hgc vi dg md hgc theo

phan loai cua WHO 2000, ddng thdi xic djnh

do xam lin ciia u vio thanh tui m|t, thin kinh,

mach miu,xam nhap gan, di can bach.

(3)

Tap chi GAN MAT VIET NAM s6 16& 17-2011 149

HL Ket qua nghi§n cihi

3.1 Cdc tip mo hpc vd dp mo hpc

Bdng 3.1. Cdc tip mo benh hpc

Tip md benh hpc Ung thu bieu md tuyen Ung thu bieu md tuyen nhii Ung thu bieu mo tuyen nhay Ung thu bieu md tuyln viy Ung thu bieu md tl bio viy Ung thu bieu md tl bio nhd Ung thu bieu md tl bao sing Cpng

n 70

18 8 7 5 2 1 111

%

63,1 16,2 7,3 6,2 4,5 1,8 0,9 100

f r f f

Nhdn xet: Ung thu bieu md tiii mat chii yeu li tip tuyen,sau dd li tip tuyen nhii, cic tip khic chiem ti le thip.

Bdng 3.2. Dp mo hpc

Do mo hoc

• • n

%

Biet hoi cao 41 36,9

Bipt hoi vira 62 55,9

Biet hoa kem 6 5,5

Khong biet hoa 2

1,8

Cong 111 100

Nhdn xefJJng thu bilu md hii mat chii ylu d do biet hda viia vi bipt hda cao Bdng 3.3. Kit qud hod mo miin dich mot sd tieong hpp kho

SoTT 1 2 3 4 5 6 7 8 9

Cac dau an mien dich CK

- -

+ + + +

-1-

+

-1-

CK7

+

CK20

-

NSE ++

++

Chromo.

+ +

Synap.

+

Ket luin

Ung thu bieu md te bio nhd Ung thu bieu mo

tl bao sang

Ung thu bieu mo tuyln kem biet. hoa

Nhdn xet: Nhd hda md miln djch da djnh dugc tip cho cic tiirdng hgp khd

(4)

150 T^p chi GAN MAT VI$T NAM so 16&17-2011 3.2. Cdc mirc dp xdm ldn vd mpt sd mdi liin quan

Bdng 3.4. Mirc dp xdm ldn cua mo u

T

n

%

Tia 6 5,5

Tib 22 19,8

T2 58 52,3

T3 25 22,4

T4 0 0

COng 111 100

Nhdn xet: Phan ldn u d giai do^n mugn T2, T3

Bdng 3.5. Xdm nhgp mgch mdu, mgch bgch huyet,

Bieu hi^n n

%

Xim nhip m^ch miu, mach bach huylt

66 59,5

Xim nhip thin kinh

29 26,1

Xim nh|p gan

25 22,5

Di cin hach 22 19,8

Nhgn xet: U xim nh|p m^ch miu vi m^icb b?ich huylt chiem ti Ip cao, sau dd Ii xim nh|p tiian kinh d thinh hii mat.

Bdng 3.6. Lien quan giira dp xdm lan u v&i xdm nhgp mgch mdu, mgch bgch huyet, thdn kinh

Dg xam lin (T) Tia Tib T2 T3 N = l l l

Xim nh|p mach miu mach bach huyet n

0 6 38 22 66

%

0 27,3 65.5 88,0 59.5

Xim nh|p thin kinh N

0 2 16 11 29

%

0 9.1 27.6 44,0 26,1

Nhdn xet: U d giai doan mugn T2,T3 cd ti 1? xam nh|p m?ich miu, mach bach huyet vi xam nhip thin kinh d thinh tiii mat cao

Bdng 3.7. Lien quan giua dp xdm lan v&i miec dp bipt hod mo u

DO xam lan

(T) Tia Tib T2 T3 COng

DO bift hoi Bi^t hoi cao

2 9 21

9 41

Bipt hoi vira 4 12 32 14 62

Bi^t hoi k£m 0 1 5 0 6

Khdng bipt hoi 0

0 0 2 2

COng 6 22 58 25 111

Nhdn xet: U cd do biet hda kem vi khdng biet tiiudng gap d T2 , T3

(5)

Tap chi GAN MAT VIET NAM so 16&17-2011 151

la

- • . S i ' * * - n ^ //)

Z T i ^ •<»-

Hinhl: L'ng line hieu mo tuven biet hoa kem a: HE xlOO: b: HMMDCK (+) x 100

2b

Hinh2: Ung thu bieu mo ti bdo nho a: HE x 200; b: HMMNSE (+) x 200

(6)

152 Tap chi GAN MAT VI$T NAM s6 16& 17-2011

Bdng 3.8. Lien quan giira dp bipt hod mo u vd xdm nhdp mgch mdu, mgch bgch huyet. thdn kinh

Dg bipt hoa

Bipt hoa CAO

n = 41 Biet hoi viia

n = 62 Biet hoa kcni

n = 6 Khong bipt hoa

n = 2 n = l l l

Xam n h | p ni^ch miu, mach bach huyet n

11 48 5 2 66

%

26,8 77,4 83,3 100 59,5

X i m nhap thin kinh N

6 16

5 2 29

%

14,6 25,8 83,3 100 26,1

Nhdn .xet: U bipt hda kem vi khdng bipt hda xam nh|p m^cb miu, mach bach huyet, xim nhip

i.

thin kinh thanh tiii mat chiem ti 1? cao ban d dg bipt hda viia vi bipt hda cao

Bdng 3.9. Lien quan giira dp bipt hod mo u vd di cdn hgch, xdm nhdp gan

Do biet hoa Biet hoa cao

n = 41 Biet hoa vira

n = 62 Biet hoa kem

n = 6 Khong biet hoa

n = 2 n = l l l

Di cin hach n

4 14

3 1 22

%

9,8 22,6 50,0 50,0 19,8

X i m n h | p gan N

2 21

1 1 25

%

4,9 33,9

16,7 50,0 22,5

Nhtin xet: U biet hda cao cd ti le di can hach vi xim nhap gan thip horn so vdi bipt hda vua, biet hda kem vi khdng biet hda.

rV. Ban luan

4.1. Tip mo hpc, dp mo hpc, hda mo miin dich.

- Tip mo hpc: phan loai md hgc ung thu bieu md tiii mat rit cd y nghia trong viec dinh gii tien lugng benh ciing nhu trong dilu tri.

Bdi vay da cd nhieu phan loai md hgc da dugc de xuit cho loai u nay nhu phan loai cua Td chiic Y tl thl gidi (WHO) nam 1978, nim 1991 va ciia Vien Giai phlu benh hgc Hoa ky nam 2004 (AFIP)(11)... D I cd sy thdng nhit cho cac nha benh hgc tren toan ciu, nam 2000

WHO da dua ra bing phan loai md benh hoc

mdi cho ung thu bilu md tiii mat. Bing phin

loai niy chi tiet ban vi thuan Igi ban khi ddi

chieu giii phlu bpnh- lim sing, djch te hoc,

phuang phip dilu trj, dong thdi neu len dugc

nhirng tien bg mdi vl sinh hgc phan hi vl gene,

hda md mien djch. Day li phan loai mdi nhit

vi dugc Sli dyng rgng rai d nhilu nude tren

the gidi (13). Ve vi the phan loai niy gdm cic

tip:

(7)

Tap chi GAN MAT VIET NAM s6 16& 17-2011 153

Ung thu bilu md tai cho - Ung thu bieu md tl bio nhin

t r

- Ung thu bieu md tuyen

- Ung thu bilu md tuyln tip rugt

- Ung thu bieu md tuyen tip nang da diy Ung thu bieu md te bio sing

Ung thu bieu md tuyen nhiy

Theo phin loai cua WHO - 2000, qua phan tich 111 trudng hgp ung thu bilu md tiii mat chiing tdi nhin thiy mig thu bilu md tuyln li tip hay gap nhit vdi 70 trudng hgp chiem 63,1% sau dd li ung thu bilu md tuyen nhu - 18 trudng hgp chiem 16,2%), cic tip khic it gap. Die biet chiing tdi gap 2 trudng hgp te bio nhd vi 1 trudng hgp te bio sing, diy li nhimg the hiem cua ung thu bieu md hii m|t. Kit qui cua chiing tdi ciing tuomg ty vdi nghien ciiu ciia Catanzano nghien ciiu 134 trudng hgp ung thu bieu md tiii mat. Trong dd ung thu bieu md

r r ^ f

tuyen chiem 67,9%, ung thu bieu md tuyen nhii -10,7%. Mdt nghien ciiu khic vdi 2893 trudng hgp ung thu bieu md tiii mat, trong dd cbii yeu li

f f /

ung thu bieu md tuyen vdi 76,43%), tuyen nhu

r f y

CO ti le thip chi cd 4,39%), tuyen nhiy 5,18%),

r f

tuyen viy 3,25% cdn cic tip khic ciing rit it gap (11).

- Dp mo hpc

Phin loai WHO 2000 phin cic miic do biet hoa cao, bipt hda vua, bipt hda kem vi khdng

f

biet hda. Bipt hda cao li khi md u cd ciu tnic hiyln chilm 95%, biet hda vira md u cd ciu tnic hiyin chilm 40 - 94%, biet hda kem ciu tnic hiyin chilm 5 - 39%, tip khdng biet hda tuyln <

5%. Theo phan do niy, kit qui ciia chung tdi cho tiiiy ung tiiu bilu md tui mat chu ylu d do bipt hda vua v i biet hda cao (47,8 vi 45,9%), loai kem biet hda chi chilm 4,5%) vi tip khdng biet hda cd ti le thip nhit - 1,8%. Theo nghien ciiu cua mdt sd tic gii ung tiiu hii m|t chu ylu li loai tuyln biet hda cao v i biet hda vija(l 1, 14).

Cac nghien ciiu ciing nhan thiy ring viec djnh tip md hgc v i do md hgc cd y nghia ddi vdi danh gia tien lugng benh (11)

=Hda mo miin dich

Trong nghien ciiu cua chiing tdi cd 9 trudng hgp chilm 8,2%) tren nhudm H&E khd xac

Ung thu bilu md tuyln viy Ung thu bilu md tuyln nhii Ung thu bilu md tl bio viy

- Ung thu bieu md tl bio nhd - Ung thu bieu md tl bio ldn - Ung thu bilu md khdng biet hda - Ung thu bieu md tuyln nang

djnh tip md hgc da dugc nhudm hda md mien djch. Trong sd niy 6 trudng cd ciu tnic hiyin it ya khdng rd ring vdi nhilu hinh thai tl bio bieu md khic nhau kem xim nhip viem ning, sau nhugm CK duomg tinh da xic djnh li ung

f f

thu bieu md tuyen kem bipt hda. 2 trudng hgp tren nhudm H &E thiy tl bio u biet hda theo hudng tl bio nhd dugc nhudm cic diu in mien djch vdi cic khang thl cd ngudn goc thin kinh nhu NSE, Chromogranin,Synaptophysin. Kit qua ci 2 deu duomg tinh manh vdi NSE, vdi Chromogranin vi duomg tinh yeu vdi Synap- tophysin, am tinh vdi CKvi da dugc xac djnh li ung thu bieu md te bio nhd.Diet biet cd 1 truong hgp tren tieu bin nhudm H&E te bio u cd bio tuomg sing nhudm PAS duomg tinh nhp, xanh Alcian (-), chiing tdi cho nhudm CK vi CK7 diu duomg tinh vi dugc chin doan la

t r f

ung thu bieu md te bio sing. Qua diy cho thiy phuomg phap nhudm H&E thdng thudng d mdt sd trudng hap khd xic djnh chinh xac dugc tip md hgc, cin phii cd su bo trg cua hda md mien djch.

2. Cdc miec dp xdm ldn vd mpt so moi lien quan

-Cdc mirc dp xdm ldn

+ Sy xim lin ciia md u vio thinh tiii mat vi cic tang cd y nghia quan trgng trong xep giai doan bpnh v i dinh gii tien lugng bpnh. Kit qui nghien ciiu cua chiing tdi cho thiy u d giai doan T2 chilm ti le cao 52,3% - hie li u da xim lin vio Idp ca ra din thanh mac tiii mat, sau dd li u d giai doan T3-22,4% - u phit triln vugt qua thanh mac xim nhap vio gan, cic co quan lan c|n nhu da day, ti- tuy, dai tring, dudng mat ngoii gan, mac ndi ldn. Dilu nay cho thiy phin ldn ung thu bilu md tui mat dugc chin doin va phau thuit ttiet dh cat bd u da d giai doan mudn. Ben canh dd cdn khdng it

(8)

1 5 4 Tap chi GAN MAT V1$T NAM so 16«fe 17-2011

trudng hgp benh d giai doan qui mudn klidng cd chi djnh mo hoac md ra nhung khdng cd khi nang cit bd u. Theo nghien ciiu ciia mgt so tic gii ciing cd ti le tuang ty (6, 8).

+Xam nhap mach miu vi mgch bgch huyet:

kit qui ngien ciiu ciia chiing tdi cho thay md u xam nhip nignh iiiau,niach bach huyet chiem ti le cao 59,5%.Chiing tdi ngliT ring phii ching do die diem ciu tnic md hgc ciia Idp dudi niem mac va Idp ca thanh thanh tiii mat Idng leo va giiu mach miu ciing nhu mach bach huylt nen dd la dilu kipn thuan Igi cho md u xam nhap. Tim hilu qua y vin chiirig tdi chua nhan dugc tii lieu nao de cap tdi vin de nay.

+ Xam nhap md thin kinh d thinh tiii mat:

quan sit ky ludng tren kinh hien vi quang hgc cic tieu ban chiing tdi phit hipn dugc 26/111 trudng hgp (26,1 %) md u cd xim nhip vio cic bd diy thin kinh d thinh tiii m|t. Cd phii vi vay mi ung thu tiii mat thudng dugc phit hipn mudn do it cd tripu chiing dau ?

+ Di can bach: tit ci cic bach dugc liy ra khi phlu thuit chiing tdi deu cit minh lim xet nghiem md bpnh hgc, ket qui cho thay chi cd 19,8%) cd di cin bach. Sd dT ti le di cin hach thip cd thl giii thieh do nhieu trudng hgp ung thu bilu md tiii mat chi dugc chin doin sau khi cd kit qui md benh hgc, trong khi trudc md thudng li tinh trang bpnh ly khic nhu sdi hay poip tiii mat nen cac phiu thuat vien it chii y den vipc nao vet bach. Theo mdt sd tic gii thi ung thu bilu md tiii mat chin doin trudc md chi khoing 10%, cdn da sd (50 - 70%) dugc

chin doin trong md v i sau md (7).

+ Xam nh|p gan: chiing tdi chin doin xam nh|p gan tren cic minh cit dugc phlu thu|t vien lay trong khi md thiy cd tdn thuang d gan, ti Ip niy li 22,5%). Nghien ciiu cua Kinjiro Sumiyoshi li 30,8%) v i hay g|p u d vung thin tiii m|t (9)

Mpt sd mdi lien quan dp xdm ldn vd dp bipt hoa cua mo u

+ Lien quan giua dg xam lin cua u vdi xim nh|p vio mgch miu, mach bach huylt, thin kinh

Chiing tdi nh|n thiy md u xim nhip mach miu, mach bach huylt, thin kinh cd ti Ip ting dan vdi giai doan cua u tu Tl din T3. Vdi xam nhap mach miu, mach bach huyet d Tl li 27,3%, d T2 ting len 65,5% v i T3 len tdi 88,0%); xim nhip thin kinh d Tl - 9,1%, T2 - 27,6% v i T 3 1 i 44,0%.

Tuomg ty xim lin cua u vio thinh hii m|t cing sau thi dg bipt hda cua md u cing giim (bing, 3.7).

+ Lien quan giira do bipt hda cua md u vdi xam nh|p mach miu, mach bach huyet, than kinh, di cin hach, gan.

Bing 3.8 cho thiy dd biet hda cua md cd lien quan rd rpt tdi sy xim nhip mach miu, mach bach huylt, xim nh|p thin kinh. Ti le xim nh|p mach miu, mach bach huyet, thin kinh ting din len khi dg bipt hda ciia md u cing giim. Dieu niy ciing nhan thiy d di cin hach vi xam nh|p gan (bang 3.9).

V. Ket luan.

1. Ung thu bilu md tiii mat chii yeu li tip tuyen(63,l%)), d do biet hda vua v i cao(55,9 va 36,9%)), u d giai doan mugn T2 - T3 (74,7%)). U xim nh|p mach miu, mach bach huylt vdi ti le cao (59,5%)), xim nh|p gan vi di cin hach chilm ti Ip ding ke (12,5% vi 19,8%)) Trong djnh tip md benh hgc can phii cd sy hd trg ciia hda md mien djch d nhihig trudng hgp klid.

2. Sy xam nhap mach miu,mach bach huylt, thin kinh cd lien quan rd ret tdi sy xim lin v i dg bipt hda cua md u. Dg xim lin ciia md u cing sau vao thanh tui mat v i do bipt hda ciia md u cing thip thi ti le xam nhap mach miu, bach bach huyet, xam nhap than kinh, xam nhap gan v i di can bach cing tang.

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Tap chi GAN MAT VIET NAM s6 16«fe 17-2011 155

Tai lieu tham khao.

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