Y H p c VigT NAM T H A N G 4 • SO 2/2013
PHAT HIEN DOT BIEN GEN KRAS VA BUAC DAU DANH GIA HIEU QUA DIEU TRj DiCH Of BENH NHAN UNG THIT DAI TRUC TRANG
Nguyen Kien D u \ Tran VSn KhanhS Pham Huy T'an\
N g u y i n T u y e t M a i ^ Nguyen Tlii V a n HongS Tran Huy ThjnhS Ta Thanh Vdn^
mutation at codon 12 and 13, type of mutation was Glyl2Asp, Glyl2Val and Glyl3Asp. After three months, treatment responses: partial response, stable disease and progress disease In the group using Cetuximab combination with chemotherapy was 1, 5 and 1 patients; In the group using chemotherapy only was:
1, 2 and 3 patients, respectively. After six months, treatment responses in the group using Cetuximab combination with chemotherapy was 1, 2 and 3 patients; in the group using chemotherapy only was:
0, 1 and 4 patients, respectively. Conclusion: using direct sequencing and Scorpions ARMS methods, the frequency of KRAS mutation in colorectal cancer patients was detected at 33.3%. Primarily evaluation of effective treatment showed tJiat Cetuximab contributed to improvement of effective treatment in patients with late-stage colorectal cancer.
Keyvirords: Colorectal cancer, KRAS mutation, targeted therapy
1. OAT V A N OE
Ung thu" dai trtfc trang la loai ung thtf dtfdng tieu hoa pho bien tren the gidi va d Viet Nam. Tai ntfdc ta UTDTT ia can nguyen gay ttf vong dtfng hang thtf hai sau ung thtf phoi [ 1 ] . So ngtfdi mac UTDTT cd xu htfdng ngay cang gia tang, nam 1991 ty le mac UTDTT la 4,3/100 000 dan, nam 1999 ty le nay la 13,3/100 000 dan [ 2 ] . 6 giai doan sdm, benh nhan khong co cac trieu chtfng dien hinh va thtfdng kho phat hien, khi da cd nhtfng trieu chtfng lam sang lam ngtfdi benh phai di kham thi benh da d giai doan muon. Phtfdng phap dieu trj ehii yeu hien nay la phau thuat ket hdp vdi hoa tri tuy theo giai doan ciia benh. Tuy nliien hieu qua dieu t n van cdn thap.
Trong nhtfng nam gan day, viec lam sang to cd che benh hpe ung thtf d mtfc dp phan ttf cung vdi nhtfng tien bp cua nganh cong nghe dtfdc pham da giiip eae nha khoa hpc ap dung thanh cong lieu phap dieu tri ung thtf tning dieh (LPDTTD) cho benh nhan UTOTT di can hoac tai phat. Thude dieu trj triing dfch trong UTDTT ed ban chat la khang the ddn ddng Cetuximab, la loai thuoc tfc ehe stf tang trtfdng va ian tran ciia ung thtf mot each dae hieu bang each tac dpng TOM T A T
Nghien ctfu nliy dUdc thUc hien vdi muc di'ch xac dinh dot bien gen KRAS d benh nhan ung thu" dai trUc trang (UTDTT) bSng phu'dng phap giai trinh tu" gen tnic tiep va Scorpions ARMS; Bu'dc dSu danh gia hi|u qua dieu tr| Cetuximab ket hpp vdi hoa chat d benh nhan UTDTT khong co dot bien gen KRAS. 24 benh nhan UTDTT du'dc xet nghiem tinh trang gen KRAS bang phUdng piiap giai trinh tU gen va Scorpions ARMS. Ket qua cho thay 8/24 benh nhan UTDTT co dot bien gen KRAS tai codon 12 va 13, dang dot bien tim thay la Glyl2Asp, Glyl2Val va GlylSAsp, 16/24 benh nhan khong co dot bien gen KRAS, Cac benh nhan khong co dot bien gen KRAS dupc lUa chpn de so sanh hieu qua stf dap irtig thuoc tai thdi diem 3 thang, 6 thang theo 2 nhom stf dung Cetuximab ket hdp hoa chat va stf dung hoa chat. Sau 3 thang, ket qua dap tfng dieu tri: dap tfng mot phan, benh on 6mh, benh tien tnen fan Iu'dt la 1/7, 5/7 va 1/7 benh nhan tren nhom stf dung Cetuximab ket hdp va 1/6, 2/6, va 3/6 benh nhan tren nhom chi stf dung hoa chat. Sau 6 thang, ket qua dap tfng dieu trj ian lUpt la;
1/6, 2/6 va 3/6 benli nhan tren nhom stf dung Cetiximab ket hdp va 0/5, 1/5, va 4/S tienh nhan tren nhom chi stf dung hoa chat.
Ttf khoa: Ung thU dai tn/c trang, dot bien gen KF^AS, lieu phap dieu tn dich
SUMMARY
DETECTION OF KRAS GENE MUTATION AND PRIMARILY EVALUATION OF EFFECTIVE TREATMENT FOR TARGETED THERAPY IN
COLORECTAL CANCER PATIENTS Objective: determine KRAS mutahon frequency in colorectal cancer patents using direct sequencing and Scorpions ARMS methods; pnmanly evaluate effective treatment of Cetuximab combinabon with chemotherapy in colorectal cancer patients without KRAS mutation. Patients and methods: 24 colorectal cancer patients were determined KRAS gene mutation using direct sequencing and Scorpions ARMS methods; compare effective treatment responses between seven-patent group using Cetuximab combination with chemotherapy and six-patent group using chemotherapy only. Results: 8/24 colorectal cancer patients, account for 33,3%, had KRAS
^Trwdng Dal hgc YHa Noi, ^ Benh vien K, ^Benh vien Daih Phan biSn khoa hpc: PGS.TS. Nguyin Thj Ha
Y HQC VigT NAM THANG 4 • SO 2/2013 len cac thu the dac hieu cho stf sinh trtfdng ciia
te bao ung thtf. Oieu nay da mang lai nhutig hy vpng rat Idn eho benh nhan UTBTT. Cac nghien ctfu thtf nghiem lam sang cho thay nhtfng benh nhan ung thtf dtfdc ap dung LPDTTD ed tien trien benh rat tdt: kieh thtfdc khoi u giam dang ke, thdi gian song keo dai hdn, stfc khde khong bj suy kiet so vdi ket qua dieu trj bang hda chat ha^
xa tri. Tuy nhien hieu qua ciia LPDTTD tren moi benh nhan la hoan toan khac nhau. Cac eong trinh nghien ctfu tren the gidi ehi ra r i n g dot bien tren gen KRAS tai vung ma hoa eho chtfc nang GTPase va dot bien gen BRAF gay nen hien ttfdng khang thudc Cetuximab trong UTDTT di can. Chinh vi vay, viec xae djnh tinh trang dot bien tren cac gen KRAS ddng vai tro quyet djnh trong viec ap dung LPDTTD, chi ed nhtfng benh nhan cd gen KRAS khdng dot bien mdi dap tfng vdi dieu t n Cetuximab. Phtfdng phap xet nghiem gen KRAS pho bien hien nay tren the gidi la ky thuat giai trinh ttf gen va Scorpions ARMSva ty le dot bien gen KF^AS dao dong ttf 35 den 42 % [3][4][6].
Tai Viet Nam, chtfa ed cong bo ve ty le dot bien gen KRAS va danh gia hieu qua dieu t n eiia eiia Cetuximab d benh nhan UTDTT. Nghien ctfu nay dtfdc tien hanh vdi muc tieu: (1) Xae djnh dot bien gen KRAS d benh nhan UTDTT bang phtfdng phap giai trinh ttf gen trtfc tiep va Scorpions ARMS; (2) Btfdc dau danh gia hieu qua dieu trj Cetuximab ket hdp vdi hoa chat d benh nhan UTDTT khong ed dot bien gen K I ^ S .
II. o6\ TUpNG VA PHaONG P H A P NGHIEN ClJTU 2.1. £>di tu'dng nghien cii'u: 24 benh nhan ung thtf bieu mo tuyen dai trtfc trang dieu tn tai cac benh vien K Ha Npi, Benh vien Baeh Mai, Benh vien Htfu Nghi.
Cac benh nhan nay dMc chan doan xae djnh dtfa vao ket qua md b^nh hpc va khong mae ung thtf nao khac.
Cae mau mo ung thtf dai trtfc trang trong parafin dtfdc xac dinh dot liien gen KRAS tai Trung Tam Nghien Ctfu Gen-Protein, Trtfdng Dai hpc Y Ha Npi.
2.2. Phu'dng p h a p n g h i e n cu'u 2.2.1. Xacdjnh dot bien gen KRAS - Ky thuat taeh ehiet DNA: Mau mo dtfdc cat lat va 6\S(ic ltfa chpn chinh xac vung te bao ung thtf du^ vao hinh anh mo benh hpc. Parafin diic
trong mau mo dtfdc loai bd bang xylen. DNA dtfdc tach ehiet theo qui trinh phenol/chloroform.
Nong dp va do tinh sach DNA dtfdc do tr£n may Nano-Drop, nhtfng mau DNA dat dp tinh sach OD 260/280 1.8-2 dtfdc stf dung de phan tich.
Ky thuat giai trinh ttf g e n : Sau khi khuyech dai exon 12, 13 ciia gen KRAS bang ky thuat nested PCR, san pham PCR dtfdc tinh sach ttf gel agarose bSng Promega Wizard SV gel clean-up system (Promega, USA), sau do dtfdc dtfa vao giai trinh ttf bang phtfdng phap BigDye terminator sequencing (Applied Bi9systems/
Foster city, USA). Trtnh ttf gen dtfdc doi ehieu va so sanh vdi trinh ttf ciia KRAS kieu hoang dai tren GeneBank (National center for biotechnology information, NCBI).
- Ky thuat Scorpions ARMS (Scorpions - Amplification Refractory Mutation System): Day la ky thuat ket hdp ciia ky thuat khuyech dai dac hieu alen dot bien (ARMS) va cong nghe Scorpions trong phan tfng Real time PCR de phat hien cac dot bien. Quy trinh ky thuat thtfc hien theo kit ciia h=ng QIAGEN.
2.2.2. C- nh gia dap u'ng dieu tri - Danh gia dap tfng dieu t r j :
Danh gia hieu qua dieu trj dtfa vao kham iam sang va can lam sang (Chup CT, MRI, PET/CT, nong dp CEA, sieu a m , npi soi...) tiiu thap dtfdc d thdi diem trtfdc khi dieu tri, sau Sm tri 3 thang va 6 thang.
Danh gia dap tfng dieu tri theo REQST 1.1:
gom 4 mtfc d p : i) Dap tfng hoan toan: cac ton thtfdng bien mat. il) Dap tfng mpt phan: giam tren 3 0 % tong dtfdng ki'nh ton thtfdng. iii) Benh gitf nguyen: khong dii tieu chuan danh gia dap tfng mpt phan hay tien trien. iv) Benh tien trien:
tang it nhat 2 0 % tong dtfdng kinh tfin thtfdng.
- Phae do FOLFOX 4 :
Oxaliplatn 85 mg/m2 titryen tinh madi ngay 1,15.
Folinic acid 200 m g / m 2 truyen tmh macli ngay 1, 2, 15, 16.
5 FU 400 mg/m2 tiem Unh madi ngay 1,2,15,16, 5 FU 600 m g / m 2 tiem tmh mach ngay 1,2, 15, 15 (22 gid).
Moi chu ky 4 tuan.
- Phac do FOLFOX 4 ket hdp Cetuximab:
Benh nhan dtfdc dieu tri phac do FOLFOX 4 ket hdp Cetuximab tiem tTnh mach lieu ban dSu 400 m g / m ^ 250 mg/m^ cho moi tuan tiep theo.
Y HOC VIET NAM THANG 4 - S 6 2/2013 III. KET QUA NGHIEN COU
3 . 1 . Ket qua x e t n g h i S m g e n KRAS.
Bang 1 . Cac danq dot bien qen KRAS Gidi
Nam Nii-
Tong n
Tile
0 $ t bien codon 12
3 2 5 5/24
Dot bien Codon 13
1 2 3 3/24
Khong dot bi£n
12 4 16 16/24
Tong n 16 8 24
Trong 8/24 benh nhan co dot bien gom 4 nam va 4 nu* (chiem ty le 33,3%); 16/24 benh nhan khong dot bien gen KRAS. 5 benh nhan dot bien is codon 12 va 3 tru'dng fiop dot bien 6 codon 13.
3.2. K i e u d o t b i e n g e n KRAS v d i v i t r i cua u t r e n d a i t r a n g . Bang 2 . Danq dot bien vdi vi trf UTDTT
Vi t r i u Oai tranq Sigma Tn/c tranq
Tong n
Tvie
B p t bien Glvl2Asp
2 1 1 4 4/8
Dot bien Glyl2Val
0 0 1 1 1/8
Dpt bien GlylSAsp
1 1 1 3 3/8
Tong n 3 2 3 8
T y l e 3/8 2/8 3/8 8/8
Tnang so 8 trtfdng hdp dot bien gen KFRAS co 4 trtfdng hdp dot bien dang Glyl2Asp, 1 trtfdng hdp ddt bien dang Glyl2Val va 3 trtfdng hpp dot bien dang Glyl3Asp; Ve vj tri cd 4 trtfdng hdp ung thtf dai trang, 2 trtfdng hdp d dai trang sigma, 2 trtfdng hidp d trtfc trang.
3.3. Oanh gia dap u'ng dieu trj Sau 3 thang dieu tri:
- ^ m M
Hoiin to^n Mot phiin dn dmh Khong x^c dinh Bleu do 1. Dap tfng sau 3 thang dieu trj
Khong cd benh nhan nao dap utig hoan toan d ea hai nhdm, nhdm ed stf dung Cetuxinrrab cd 1/7 benh nhan dap litig mpt phan, 5/7 benh nhan on djnh, 1/7 benh nhan ben trien; nhom khong stf dung Cetuximab CO 1/6 b&ih nhan dap litig mot phan, 2/6 benh nhan on djnh va 3/ benh nhan tien trien.
Sau € tiling dieu tri: Qac b§nh nhan tiep tuc dtfdc so sanh hieu qua dieu trj thudc, tuy nhien
nhom stf dung Cetuximab ket hdp hda chat chi cdn 6 benh nhan va nhdm stf dung hda chat ehi eon 5 benh nhan stf dung thuoc dii 6 thang.
Bieu dd 2. Dap tfng sau 6 thang dieu tri
Y HQC VigT NAM THANG 4 - S6" 2/2013
Khong CO benh nhan nao dap utig hoan to^n phan con lai ciJa dai trang. Chu'a thay co sii khac cf ca hai nhom, nhom co sCr dung Cetuximab co biet ro ret ve ty le dpt bien gen KRAS 6 nhiilig 1/6 tri/dng hop dap utig mpt phan, 2/6 tru'dng ngu'di benh ung thu' tn/c trang va ung thu' dai hdp on dinh, 3/6 tru'dng h(?p tien trien; nhom trang nhu'ng neu ti'nh tren tong chieu dai giai khong sif dung Cetuximab co 1/5 tn/dng hdp on phau cua rupt gla thi t / le dot bien gen KfWS i dinh, 4/5 tru'dng hdp tien trien va 1/5 tru'dng hdp nhu'ng ngu'di benh ung thu' tn/c trang co cao hcfn den thdi gian theo doi deft 2. nhffng doan khac.
Cac nghien cu'u tren the gidl du'dc cong bo
IV. BAN LUAN "^eu cho thay thuoc dieu trj dich co tac dyng roNhUng nSm gan day, LPDTTD dang ia niem ret_ tren nhom b^nh nhan UTDTT cd gen KRAS hy vpng mdi cho nhO'ng benh nhan UTDTT d gial khong dpt bien con tren nhdm benh nhan ung thi/
doan mupn. Nhieu cpng trinh nghien cii'u tren the ^?' ^"f^ ' ^ n g cd gen KRAS dot bien thuoc nay gldl da chirng minh thuoc dieu tri dich chl mang ^*^"9 m tac dung [3][2]. O nu'dc ta, thuoc nay iai idi ich cho benh nhan cd gen KRAS the khong f"* ''"'9^ sir dung de dieu trj benh nhan UTBTT dot bien. Viec xac djnh tinh trang gen KRAS trd ^'°"9 "'^^ "^i "Sm gan day. Van de gia thanh, tac thanh mpt hu'dng dan quan trong cho thay thuoc ''^hg phu cua thuoc va hieu qua dieu tri tren tru'dc khi cd chi djnh cho benh nhan diing thuoc ^"^ "^^" UTOTT Viet Nam chuS du'dc kiem dieu tri dich. Ty ie dot bien gen KRAS dao dong TiJ'ng nen cac thay thuoc cdn chua chi tJinli tir 35% den 43% [3][4][7], dot bien d codon 12 "^'^''- Trong nghien ciJu nay chiing toi bu'dc dau va codon 13 chlem chii yeu [7]. Van Cutsem va ''f"*' 9'^ ^^P "^9 ""eu trj ciia benh nhan UTOTT cpng 5/ nghien cu'u tren 540 benh nhan thay ty le ™ Sen KRAS khong dot bien vdl thuoc dieu tri dot bien gen KRAS la 35,6% [4]. Nghien cu'u ciia * ' * Cetuximab ket hdp hda chat sau 3 thang va Tejpar va Livere phat hien ty ie dot bien ia gen ^^ ^ thang dieu trj. Ket qua sau 3 thang va 6 KRAS lan Iu'dt la 37,2% va 43% [3][5]. Ket qua thang: khong co benh nhan nao dap utig hoan nghien cii'u nay cho thay co 8/24 tru'dng hdp dot toan d ca hai nhdm, nhdm cd sir dyng Cetuximab bien chia deu cho ca hai gidi, chlem ty le 33,3%, <:° tV '? benh nhan dap Otig mpt phSn va benh on thap hdn cac cong bo tru'dc day. Dot bien codon '^inh cao hdn so vdl nhdm khdng sil dung 12 la 5/8 benh nhan va dot bien codon 13 la 3/8 Cetuximab. Trong nghien cuU CRYSTAL va 01=115 benh nhan. Nghien ciru nay phat hien hai dang ^^ chutig minh rang them cetuximab ket hdp vdi dot bien codon 12 ia Giyl2Asp va Giy 12Vai dang hda chat (FOLHRI hoac F0LF0X4, tu'dng ijtig) dot bien codon 13 la Glyl3Asp trong so cac dang '^."^ 9iam nguy cd tien trien ciia benh va tang al dot bien thu'dng gap. Nghien ciru nay sir dyng ca ^9< phan img, so vdi hda chat mpt minh, doi iS hai phu'dng phap giai trinh tU tryc tiep va nhffng ngu'di benh cd gen KRAS khong dot bien.
Scorpions AMRS de xac djnh dot bien gen KRAS. Nghien cffu ciia chung tdl vdi thdl glan theo doi Vdl u'u diem ciia phu'dng phap Scorpions AMRS ™n ngan va so lu'dng benh nhan chffa nhieu cho phep phat hien chi'nh xac dot bien gen trong nhffng vdi ket qua sd bp bffdc dau cho thay cac mau mo phan tich cd ty le te bao ung thff Cetuximab phoi hpp vdl hda chat gdp phan cai thap va alen dot bien chiem t/ ie rat nhd (khoang thien hieu qua dap img trong dieu trj ung thff dai 1%) va cho ket qua chinh xac, cd do tin cay cao. ^'<f'^ 'rang tal phat hoac di can ma khdng the clii Ket qua ve ty ie dot bien gen KRAS ciia chiing toi t'inh phau thuat dffdc.
thap hdn nhii'ng cong bo tren the gidi cd the la
mot thong tin tich cffc doi vdi ngffdi Viet Nam neu V. KET lUAN
Jli,l^™^"Sl"^^''"'v'"'''^"3 ainh vdi cdmau idn Sff dung ky thuat glai trinh tff gen va hdn trongthdi gian tdl. _ Scorpions ARMS, nghien cffu da phat hiin duBc ty
Sff hen quan cua yi tri khoi u vdl dot bien le dot bien gen KRAS d ngffdi benh ung thff dai
?hn S i ™ ^ " 'Z^^f- ^i'""^""'' '^ "^^"9 "f ^'^'^ '^^"9 1= 33,3%. Banh gla hieu qu5 dfeu tri hdn uno t h T f l l - ? - ^ ' f j ^ " ? - " " 9.^" '^'^S '^° <^"= *"°'<: hffdc dau cho tha-y Cetuximab gop cia n t ^ r r, ri?'" ^rl^Il-^^'^ " ' ' "^'"^" ^^" P*''^" « i *ien hieu qua dap ulig dieu tri d nguS benh Jno ?h ? tr r^ ' ' ' "-!?»" ? ' K - ^ ' ^ ^ '^ ^'^ * "^"^ ^"9 ^ ' ^ ' ^ ' ^ ^ ' ^ trang giai doan muon.
benh ung thff trffc trang, 2/8 d benh nhan ung . . a » . .
thff dai trang sigma va 3/8 benh nlian ung thff d
Y HQC VigT NAM T H A N G 4 - S 6 2/2013
TAI u e u T H A M KHAO
1. Doan Hu\i Nghj. (1993) Nghi§n ctfu xSy dung
• phac dS dieu tn ung thu" dai tru'C trang. Dai Hoc Y Ha Noi, (2-4),
2. Pham Hoang Anh va cpng stf (1993), "Ung thu" tren ngtfdi Ha Noi 1991-2000" Tap chi y hoc 7, (2-24).
3. Lievre A, Bachet JB, Le Corre D, et., al. (2006) KRAS mutation status is predictive of response to cetuximab therapy in colorectal cancer. Cancer Res. 66(8)13992-5.
4. Van Cutsem E, Lang I, D'haens G, et., al. (2008) K-FV\S Status and efficacy in the first-line treatment of patiens with metastatc colorectal cancer (mCRC) with roUURI with or without Cetuximab: The CRYSTAL experience. J Oin Onool. 26:2
5. Tajpar S, Peeters M, Humbler Y, et., al.
(2008) Relationship of efficacy with K-RAS status (wild type versus mutant) in patients with innotecan-refactory metastatic colorectal cancer (mCRC), treated witj irinotecan (q2w) and escalating doses of cetuximab (qlw): The EVEREST expenence (preliminary data). J Clm Oncol. 26:4001.
Bokemeyer C, Bondarenko I , Hartmann 31, et., al. (2008) K-RAS status and efficacy of first- line treatment of patiens with metastatic colorectal cancer (mCRC) with FOLFOX with or without Cetuximab: The OPUS experience. J Clm Oncol. 26:4000.
Brink M, de Goeij AF, Weijenberg MP, et., al.
(2003) K-ras oncogene mutations m sporadic colorectal cancer in The Netherlands Cohod Study.
Carcinogenesis. 24(4):703-10.
NGHIEN CiKU GIA TRj CUA CAC TEST Bi VOTI Dj NGUYEN DERMATQPHAGOIDES PTERONYSSINUS O T B I N H NHAN VIEM M O I Dj IJfNG
Pham Van Manh**, Nguyin Xuan Bai*, Pham Van Thu'c**
TOM TAT
Dat van tfe: Cac test bi la phUdng phap de iam, CO hieu qua cao thUdng du'dc phoi hdp vdi test in vivo Ichac frong chan doan xac dinh dj nguyen D.pte gay benh VMDl/. Myc tieu: Oanh gia gia tn cua cac test bi trong chan doan dac hieu benh VMDU" do di nguyen D.pte; So sanh do nhay va do dac hi§u cua 2 test nay de khang dinh them gia tn neng cua moi test. Ooi tu'dng va phifdng phap nghien ctfu: Gom 120 benh nhan VMOU* vdi D.pte nghien ctfu mo ta cat ngang, tien ctfu tai Benh vien DHY Hai phdng. Ket qua: Test lay da: do nhay 71,67%, do dSc hieu 93,3%. Test noi bi: do nhay 95%, dp dac hieu 90%.
So sanii 2 test: test npi bi vdi di nguyen D.pte cho dp nhay cao hdn test lay da (p<0,001). Dp dac hieu cua 2 test nay khong co sii khac biet. Ket luan: Phoi hop giij^ 2 test lay da va test npi bi trong chan doan VI^^DU*
vdi di nguyen lam tang dp chinh xac cua chan doan.
SUMMARY
STUDYING THE VAUDIY OF SKIN TESTS IN PATIENTS WITH ALLERGIC RHINITIS SENSITIZED TO DERMATOPHAGOIDES
PTERONYSSINUS
Introduction: Skin test that is easy and
effective usually coordinated with other in vivo test to make diagnosis of allergic immunologic diseases to Dermatophagoides pteronyssinus (Dp). Objective: to evaluate the validity of skin test in the specific diagnosis of allergic rhinitis to Dp, compare sensitivity and specificity of 2 tests to enhance the validity of eacii test. Patients and Method: 120 patients with allergic rlimitis to Dp were enrolled in the descnptive and prospective study at Haiphong Medical University Hospital. Results: Pnck test: sensibility was 71.67%
and specificity 93.3%. Intracutaneous test: sensibility was 95%, specificity 90%. Sensibility of intracutaneous test was greater than that of prick test. No difference can be found in the companson specificity of both tests. Conclusion: The combination of intracutaneous test and prick test to make specific diagnosis of allergic rhinitis revealed highly effective.
I.
OAT V&N OETrong may chuc nam gan day, stf phoi hdp gitfa cac chuyen Ichoa trong nghien ctfu viem mui di tfng (VMOU") da mang lai nhtfng thanh cong Ithong nhtfng ve chan doan dac hieu, ma con ve ket qua dieu tri. De chan doan mpt benh di tfng nhat thiet phai qua cac btfcic: khai thac tien stf dj
* Tnfdhg DH Y Thai Binh; ** TrWdng DH Y Hal Phong Phan bien khoa hgc: GS.TS. Vu Thj Minh Thyc