Y HOC VIET NAM THANG 10 - SO 2/2010
NHAN XET KET QUA BLf6C DAU VE HIEU QUA GHEP TE GOC TLf THAN TRONG DIEU TRj MAT DOAN Xl/ONG VA NGAN CHI
, i ^ J ^ Nguyin Van Lugng, D6 Tien Dung, Nguyin The Binh Nguyin Vii Tuan Anh, Nguyin Viet Hiing*
; ^ l i t i ; n U
T O M T A T ; , , „ , ;
Ket xu'dng cang dan trong keo dai chi hoac l<et xu'dng hai d thudng yeu cau thdi gian dai dieu tri. Chung tdi da phat trien mdt ky thuat mdi ghep te bao gdc (TBG) tuy xu'dng tg than vao o ket xu'dng cang dan ciia xUdng chay. Tir thang 3/2008 den thang 7/2010, 22 benh nhan (BN) (vdi 32 xUdng chay) du'dc keo dai chi hoac ket xu'dng hai d tai benh vien ciia chung tdi va ghep te bao gdc tuy xu'dng tii than khi het giai doan cang dan. Tudi trung binh cua benh nhan la 29,77 tudi (19-45 tud'i). Do dai trung binh ciia d cang dan la 6,96± 2,33cm. 18 BN vdi 26 xu'dng chay da lien xUdng va da du'dc thao bd cd dinh ngoai ma khdng cd bien chiing. Thdi gian lien xu'dng trung binh la 27,5 ±2,5ngay/lcm d nhdm keo dai chi va 35,1±4,2 ngay/lcm d nhdm ket xu'dng hai d; 4 BN dang trong qua trinh dieu tn.
Thdi gian lien xu'dng trung binh du'dc rut ngan hdn so vdi cac nghien cu'u khdng sii dung te bao goc.
Mac du, day chi la ket qua bu'dc dau, ghep khdi te bao gdc tii than vao 6 ket xu'dng cang dan da rut ngan du'dc thdi gian lien xu'dng cung nhu' thdi gian dieu trj bang each thuc day qua trinh hinh thanh xu'dng mdi tai 6 ket xu'dng cang dan.
Tli khoa: Mat doan xu'dng, ngan chi, Te bao gdc tuy xu'dng, keo dai chi, ket xu'dng hai 6.
or bone transport require long treatment period.
We developed a new technique of transplantation of autologus bone marrow stem cells in distraction osteogenesis of tibia. From March, 2008 to July, 2010, 32 tibias (22 patients) were lengthening or transported in our hospital and were transplanted cutanuos autologus bone marrow stem cells when distraction period was finish. The average age was 29,77 years (19-45 years). The average amount of tibia lengthening was 6,96± 2,33cm. 26 tibias (18 patients) were consolidation and were removed external fixation without complications. The average healing index was 27,5±2,5 days/lcm in the leg lengthening group and 35,1±4,2 days/lcm in the bone transport group, 4 patients was during treatment. The average healing index was shorterned than that of other research without using stem cells.
Although these result are still preliminary, transplantation of autologus bone marrow stem cells in distraction osteogenesis of tibia could shortened the consolidation and the treatment period, by accelerating new bone formation in distraction osteogenesis.
Keyword:Bone defect, short limb, bone marrow stem cells, leg lengthening,bone transport
SUMMARY 'iO
The preliminary result of transplantation of autologus bone marrow stem cells in treatment of bone defect and short limb.
Distraction osteogenesis in leg lengthening
I. OAT VAN OE
Phuong phap ket xuong cang dan, dugc Ilizarov thuc hien tir nam 1952, dl dilu tri cho nhiing BN bi ngan chi va mat doan xuong d than xuong dai. Nhd nhiing uu diem ciia phuong phap ket xuong cang dan ma nd
' Vien Chdn thuang chinh hinh, BV Trung uang Qudn doi 108
da dugc ap dung rdng rai tren the gidi va da dem lai kit qua rat kha quan. Tuy nhien, keo dai chi va kit xuong hai d theo phuong phap kit xuong cang dan cdn ban che do la thdi gian mang khung cd dinh ngoai dai, gay khdng it khd chiu va phien toai cho ngudi benh (1,3).
Tir nam 1990 den nay, tai Vien chan thuong chinh hinh, Benh vien Trung uong Quan dgi 108, chiing tdi da ap dung phuong phap kit xuong cang dan ciia Ilizarov de keo dai chi cho hon 300 BN bi ngan chi va ket xuong hai d cho hon 100 BN bi mat doan xuong. Qua ket qua dat dugc da chiing td tinh uu viet ciia phuong phap. Tuy nhien, chung tdi ciing ludn dat suy nghT lam sao riit ngan dugc thdi gian lien xuong tai d cang dan de bd khung cd dinh ngoai sdm hon.
Trong nhiing nam gan day, nghien ciiu ve TBG la mdt trong nhiing chu de dugc quan tam nhieu nhat va dat dugc nhirng ket qua kha quan trong nghien ciiu y sinh hgc.
TBG, mdt loai te bao dac biet cd kha nang tu tai tao mdi va biet hda thanh nhiing te bao chuyen biet trong nhiing dieu kien nhat dinh.
Cac nghien ciiu iing dung vai trd cua TBG trong dieu tri cham lien xuong, khdp gia, mat doan xuong, hoai tir vd khuan chdm xuong diii, tren ddng vat thuc nghiem va tren ngudi budc dau da cd ket qua rat kha quan (2,5,6).
Tren co sd nhiing thanh cdng trong nghien ciiu ve te bao gdc tai benh vien 108, chiing tdi da tien hanh nghien ciiu de tai nay nham muc dich: "Ddnh gid hiiu qud lien xuang cua ghep ti bdo goc ldy tie mdu tdy xuang tu thdn vdo 6 kit xuang cdng ddn trong keo ddi chi vd kit xuang hai 6".
II. Ddl TUONG VA PHUONG PHAP NGHIEN COU L Doi tugng nghien cuu.
22 BN dugc phau thuat keo dai chi hoac kit xuong hai d (IBN bi ngin chi tren 3 cm
va 8 BN dugc keo dai chi nang chieu cao, 11 BN mit doan xuong chay tren 3cm). Nhirng BN nay sau khi hit giai doan cang dan keo dai xuong dugc ghep khdi TBG lay tir mau tuy xuong tu than vao d cang dan. Thdi gian nghien eim tir thang 3/2008 din 7/2010.
2. Phuotig phap nghien cuu. Thuc hien theo phuong phap tien eiiu, theo ddi dgc.
2.1. Khdm lua chon benh nhdn
Chgn nhimg BN mat doan xuong va ngan chi da dugc lam phau thuat ket xuong hai d hoac keo dai chi, vira bet giai doan cang dan, ma khdng cd bien chiing nhu: nhiim triing ehan dinh, bien dang true chi, long khung cd dinh...
2.2. Ky thudt thuc hien
- BN sau khi dugc gay te tuy sdng dugc nam sap tren ban md. Kip lay mau tuy xuang ciia khoa huyet hgc tien hanh lay mau tuy xuong d xuong chau bang kim cd ndng, dudng kinh 2,4 mm va hiit ra bing bom tiem 20 ml,
- 250- 300 ml mau tuy xuong lay dugc, sau dd dugc tach bang phuong phap ly tam vdi may tu ddng ASTEC 204 de loai bd cac thanh phan nhu: mo, hdng cau, tieu cau...;
cdn lai khoang 30 ml chiia khdi TBG, gom:
te bao gdc CD 34+, te bao don nhan,...(Lay mau tuy xuong va tach te bao gdc do khoa huylt hgc, Benh vien TWQD 108 thuc hien).
- Sau chgn TBG, BN dugc ghep khIi TBG vao d cang dan. Ky thuat ghep: Duoi man tang sang, dam kim vao khoang trong xuong do qua trinh cang dan tao ra, tiem 30ml dung dich chiia te bao gdc vao d cang dan xuong. Vi tri tiem 2 hoac 3 diem hiy theo doan xuong cang dan dai hay ngan (day la each tiem nhdm nghien cuu dl ra). Vdi nhiing BN keo dai chi dl nang chilu cao, 6 cang dan de keo dai d ca hai cing chan nen chiing tdi tiem cho moi d cang dan la 15 ml dung dich chira TBG.
Y HOC VIET NAM THANG 1 0 - 8 0 2/2010
2.3. Chdm soc, theo doi sau ghep khoi te bdo gdc, ddnh gid kit qud..
- Sau ghep TBG, benh nhan dugc dimg khang sinh du phdng va ra vien sau 3- 5 ngay. Sau ghep TBG 4-6 tuin, BN dugc tap ty nen tren chi benh dl tranh gay vd co hgc ciia qua trinh lien xuong va tai tao md.
- Dinh ky mdi thang cac BN den kiem tra danh gia dien bien lien xuong bang chup Xquang va kiem tra lam sang den khi lien xuong va thao bd cd dinh ngoai.
- Danh gia lien xuong d d ket xuong cang dan bang thdi gian lien xuong trung binh cho 1cm keo dai theo tieu chuan ciia Ilizarov. Thdi gian lien xuong trung binh cho 1cm keo dai tinh bang sd ngay tir khi elt xuang dat cd dinh ngoai de keo dai cho den thdi diem lien xuong chia cho sd cm ciia doan xuong dugc keo dai them. Thdi diem lien xuong dugc xac dinh khi: BN thay d can xuong khdng dau khi di lai, tren phim chup XQ quy udc xuong chay cd it nhat 3 thanh xuong da lien vdi mat do can xuong ldn hon mat do tai dng tuy d hai dau xuong lanh d phia tren va phia dudi d can xuong.. Thdi gian nay dugc so sanh vdi thdi gian lien xuong trung binh cua tac gia Dd Tien Diing, Nguyen Van Tin da tdng ket trong luan an tien sy cua minh (Day la hai nghien ciiu ket xuang cang dan vdi ky thuat gidng ky thuat ciia chiing tdi tai khoa ciia chiing tdi nhung khdng su dimg TBG) va mdt sd tac gia khac tren the gidi.
- Cac bien chiing xay ra trong va sau khi ghep tl bao gdc va sau khi thao cd dinh ngoai.
III. KET QUA NGHIEN CCfU / Dac diim s6 li$u thdng ki.
1.1. Tudi cua binh nhdn.
Tudi trung binh la 29,77 tudi (19-45 tudi); trong dd tudi trung binh cua nhdm keo
dai chi la 25,64 tudi va ciia nhdm ket xuong 2 d la 33,9 tudi. Nam: 12 BN, nir 9: BN.
1.2. Do ddi trung binh cua 6 cdng ddn.
Do dai trung binh ciia d cang dan ciia nhdrri nghien ciiu la 6,96±2,33cm, trong dd do dai tmng binh ciia d cang dan ciia nhdm keo dai chi va nhdm ket xuong hai d lln lugt la 7,29±l,73cm va 6,27±3,47cm. Sd d cang dan dai 6cm-10cm chiem 23/32 d, sd d cang dan dai tren 15cm la 1 d (1/32 d), cdn lai la 8 d cd chieu dai 3-5 cm.
1.3. Nguyen nhdn gdy ngdn chi
Nhdm ket xuong hai d deu cd nguyen nhan gay ngan chi la do di chiing chan thuong. Nhdm keo dai chi cd 1 BN ngan 1 chi do di chiing bai liet tir nhd, cdn lai 10 BN dugc keo dai chi de nang chieu cao.
1.4. Thai diem ghep ti bdo goc trung binh sau thai diem hit cdng ddn Id 6,2 ngdy.
1.5. Thai gian ndm viin trung binh la 3,7 ngay (3-5 ngay).
2. Kit qud liin xuang trong keo ddi chi vd kit xuang 2 6.
2.1. Thai gian liin xuang trung binh.
Ket qua lien xuong dugc danh gia tren 26 d ket xuong cang dan (cua 9 BN keo dai chi va 9 BN ket xuong hai d) da lien xuong da dugc thao cd dinh ngoai, cdn 6 d cang dan (ciia 2BN keo dai chi va 2 BN ket xuong hai d) chua du thdi gian theo ddi de danh gia ket qua.
Thdi gian lien xuong trung binh cila d ket xuong cang dan cua ca nhdm benh nhan nghien ciiu la 31,1 ±3,9 ngay, trong dd cua nhdm keo dai chi la 27,5±2,5ngay/lcm va ciia nhdm ket xucmg hai d la 35,1 ngay/lcm.
Cd su khac biet giiia thdi gian lien xuong trung binh cua nhdm keo dai chi va nhdm ket xuong hai d cd y nghia thdng ke vdi p<0,05.
2.2. Moi lien quan giiea thai gian liin xuang trung binh vd chieu ddi 6 cdng ddn.
Thdi gian lien xuong trung binh cua cac nhdm d cang dan dai 3-5cm, 6-10cm, tren 15 cm lan lugt la 36 ngay/cm, 30 ngay/cm, 27,06 ngay/cm. Su khac biet nay khdng cd y nghia thdng ke.
2.3. Moi lien quan giua thai gian lien xuang trung binh theo thdi diem ghep te bdo goc
Thdi gian lien xuong trung binh ciia nhdm dugc ghep TBG sau 3-4 ngay, 5-7 ngay, 8-10 ngay lan lugt la 29,1 ngay, 30,2 ngay, 31,6 ngay. Khdng cd su khac biet ve thdi gian lien xuong trung binh theo thdi diem tiem te bao gdc.
2.4. Cdc bien chung vd cdch khac phuc.
Chiing tdi khdng gap trudng hgp nao bi tu mau, nhiem khuan tai d cang dan hoac chen ep khoang tai cang chan ciing nhu dau keo dai tai noi lay mau tuy xuong. Bieu hien ret run sau tiem, ban dat san, man ngiia sau tiem cd 8 benh nhan. Nhiing benh nhan nay deu dn dinh sau xir tri bang cac thudc thdng thudng. Khdng cd trudng hgp nao bi gay lai d ket xuong cang dan sau thao cd dinh ngoai.
III. BAN LUAN
1. Hieu qua lien xuotig ciia khoi te bao goc khi ghep vao 6 cang dan.
1.1. Hiiu qud liin xuang cda khoi TBG khi ghep vdo o cdng dan trong keo ddi chi
Thdi gian lien xuong trung binh ciia nhdm keo dai chi la 27,5±2,5 ngay/ cm.
*So sdnh vai cdc tdc gid trong nuac: Do Tien Dung (1) da keo dai chi cho 101 BN vdi ky thuat gidng chung tdi nhung khdng tiem te bao gdc, mire keo trung binh la 5,8cm; thdi gian lien xuong trung binh la 39 ngay/cm keo dai. Nhu vay thdi gian lien xuong trung binh ciia d cang dan giam di cd y nghia thdng ke khi ghep te bao gdc vao d cang dan.
Vi trong giai doan cang dan, mdi cm xuong cang dan cin 10 ngay, nen neu so sanh thdi gian liln xuong trung binh tir khi ghep TBG thi thdi gian liln xuong da dugc riit ngan dang kl (17,5 ngay/cm so vdi 29 ngay/cm)
* So sdnh vai cdc tdc gid tren the giai:
Dasin J.P. (1) keo dai chi d cang chan cho 57 BN, miic keo trung binh la 6,7cm, thdi gian lien xuong trung binh la 42 ngay/cm.
Pouliquen (1) keo dai chi d 57 xuong chay.
Miic keo dai trung binh la 5,23cm; thdi gian lien xuong trung binh la 40 ngay/cm. Tre T.
(1) keo dai chi d 45 BN, miic keo dai trung binh 5,4cm; thdi gian lien xuong trung binh la 45 ngay/1 cm. So sanh vdi cac tac gia tren the gidi cho thay, thdi gian lien xuong trung binh nhdm keo dai chi ciia chiing tdi thap hon.
* So sdnh vai tdc gid Kitoh H. Tac gia nay ghep TBG tmng md lay tir tuy xuong tu than sau khi nudi cay vao d cang dan trong keo dai chi. Thdi gian lien xuong tmng binh la 28,6±7,07 ngay/ 1cm vdi do dai tmng binh ciia d cang dan la 8,3 ±1,23 cm (6). Nhu vay thdi gian lien xuong tmng binh ciia nhdm keo dai chi trong nghien ciiu cua chiing tdi tuong duong vdi ket qua nghien ciru cua Kitoh H.
1.2. Hiiu qud liin xuang cua khoi te bdo gdc trong kit xuang hai o.
Thdi gian lien xuong trung binh trong ket xuong hai d la 35,1± 4,2 ngay/cm.
* So sanh vdi cac tac gia trong nudc.
Nguyen Van Tin (3) ket xuong hai d vdi ky
thuat gidng chiing tdi cho 30BN, ket qua la
thdi gian lien xuong trung binh cho 1 cm
xuong cang dan la 45 ngay. Nhu vay, thdi
gian lien xuong tmng binh trong nghien ciiu
ciia chiing tdi ngan hon so vdi nghien ciiu
ciia tac gia Nguyin Van Tin vdi p<0,05. NIU
so sanh thdi gian lien xuong tinh tir khi ghep
TBG thi thdi gian liln xuong da dugc riit
ngin dang ke (25,lngay/cm so vdi 35 ngay cm)
Y HOC VIET NAM THANG 10 - 5 0 2/2010
So sanh vdi cac tac gia tren the gidi. " - -
Bdng 1. So sdnh thai gian liin xuang trung binh vai cdc tdc gid khde.
Tac gia Sen Cierny Dagher
Green Pa ley Chiing tdi
Do dai 6 cang dan (cm) 5
6,4 6,3 5 10 6,27
Thdi gian lien xu'dng trung binh (thang/cm)
1,4 1,6 1,8 1,9 2,1 1,16
Bang 1 cho thay thdi gian lien xuong trung binh trong nghien ciiu cua chung tdi ciing thap hon dang ke so vdi ket qua ciia cac tac gia khac.
Nhu vay, khdi TBG khi dugc ghep vao d cang dan trong ket xuong hai d cd vai trd lam tang nhanh qua trinh lien xuong ciia d cang dan.
1.3. So sdnh hiiu qud liin xuang cda khoi ti bdo goc doi v&i o cdng ddn trong kit xuang hai o vd trong keo ddi chi.
Thdi gian lien xuong trung binh d nhdm keo dai chi thap hon so vdi nhdm ket xuong hai d, su khac biet nay cd y nghia thdng ke.
Dieu nay cd the giai thich la do nhdm ket xuong hai d cd vi tri d cang dan tuy thudc vao tinh trang xuong va vi tri khuyet xuong, phan mem quanh d cang dan thudng xau anh hudng den nudi duong ciia d cang dan (cd 3 BN dugc tao hinh bang vat vi phau).
2. Cach ghep khoi te bao goc va vai tro cac thanh phan cua khoi te bao goc.
Theo nhiing tai lieu ma chung tdi cd dugc, chung tdi la nhdm nghien ciiu duy nhat thuc hien ghep khdi te bao gdc lay tir mau tuy xuong tu than theo phucmg phap ly tam vao d kit xuong cang dan. Ngoai ra, tac gia Kitoh. H. (6) ghep TBG tmng md liy tir tuy xuong tu than sau khi nudi ciy va plasma giau tilu clu vao d cang dan trong keo dai chi.
Da cd nhilu tac gia ghep TBG tuy xuong sau khi dugc ly tam giong chiing tdi va diu cho ring day la phuong phap an toan va khoi
TBG sau khi tach dugc cd mat do sd lugng cac TBG duoc tang len nhieu lan (2,4,5).
Chiing tdi tien hanh tiem TBG vao d cang dan ngay sau khi ngimg cang dan. Ket qua cho thay khdng cd su khac biet ve thdi gian lien xuong tmng binh khi ghep TBG d cac thdi diem sau ngimg cang dan 3-4 ngay, 5-7 ngay, 8-10 ngay. Chiing tdi cho rang d cang dan d thdi diem ngay sau ngimg cang dan cd cac cau tnic nang do lam noi cu tni cho te bao gdc phat trien sau khi dugc ghep, ddng thdi day ciing la thdi diem d can xucmg cd nhieu cytokin va cac yeu td kich thich qua trinh lien xuong.
Chung tdi cQng nhat tri vdi Kitoh H. ve
each ghep TBG true tiep. vao d cang dan
bang each tiem true tiep khdi TBG vao d
cang dan. Tuy theo do dai cua d cang dan ma
ta cd the tiem 2-3 diem dgc theo mat tmdc
mao chay dudi hudng dan ciia man XQ tang
sang, d thdi diem ngay khi ngimg qua trinh
cang dan, khi tiem qua vd xuong d cang dan
ta cd cam giac nhu xuyen qua 1 vd triing. Vi
vay, ky thuat ghep khdi TBG vao d cang dan
la don gian, nhanh chdng, an toan. Do sd
lugng TBG dao ddng tuy timg ca the va hien nay cd rit it nghien ciiu ve sd lugng TBG can thilt phai ghep nen chiing tdi ap dung chung cho tit ca BN thi tich tuy xuong liy va ghep la nhu nhau. Chiing tdi khdng thiy cd su khac biet vl thdi gian liln xuong tmng binh d cac BN cd do dai d cang dan khac nhau.
Cach ghep khdi TBG ciia chiing tdi da cho kit qua liln xuong cua d cang dan rit kha quan. Tuy nhien, chiing tdi thiy rang trong nhiing nghien ciiu tiep theo can nghien cuu sau hon vl mdi lien quan giiia mat do/ sd lugng TBG dugc ghep vdi ket qua lien xuong ciia d ket xuong cang dan de tim ra mat dd/sd lugng tdi uu TBG cin ghep vao d ket xuong cang dan.
* Vai tro cua cdc thdnh phdn cua khoi ti bdo goc tu thdn.
Khdi t l bao gdc tuy xuong cd cac thanh phin cd kha nang kich thich qua trinh lien xuong: TBG tnmg mu, TBG tao mau, te bao don nhan khac ma mdt sd te bao nay la ngudn gdc ciia cac cytokin kich thich qua trinh tao mach mau va tao xuong (2,5).TBG trung md thudng dugc nen vao cac vat mang nhu hydroxyapatid va tricancium phosphate hoac xii xdp... de dieu tri cac khuyet xuong ldn tren ddng vat (2,5). Tren ngudi, TBG tmng md sau khi nudi cay dugc Quarto R nen vao xir xdp de dieu tri thanh cdng 3 BN khuyet xuong ldn tir 4-7cm. Mastumoto T bang nghien ciiu thuc nghiem cho rang TBG tao mau tiiy xuong CD34-I- cd vai trd tang cudng qua trinh lien xuong bang thdng qua vai trd hinh thanh vi mach mau mdi ciia d gay va qua trinh tao xuong tai d gay. Nhu vay ca TBG tao mau va TBG trung md diu tham gia thiic day qiia trinh lien xuong cua d cang dan trong keo dai chi va kit xuong hai 6.
IV. KET LUAN
Ghep khdi t l bao gdc tu than cd hieu qua lam tang kha nang liln xuong cua d ket xuong cang dan trong keo dai chi va ket xuong hai d. Thdi gian liln xuong tmng binh ciia nhdm keo dai chi la 27,5±2,5 ngdy/cm, cua nhdm kit xuong hai d la 35,1 ± 4,2 ngay/cm.
Day la mdt phuong phap dieu tri cd ky thuat don gian, an toan, de thuc hien.
TAI U E U THAM K H A O .
1. Do Tien Dung. Dieu chinh sir chenh lech dp dai hai chi dudi bang phau thuat keo dai chi theo nguyen ly cua Ilizarov. Luan an tien sy y hgc, 2001, Hgc vien quan y.
2. Nguyen Manh Khanh, Nguyen Tien Binh, Nguyen Thj Thu Ha. Ghep te bao goc tuy xuong tu than dieu trj khdp gia than xuong chay. Tap chi Y dugc hgc quan sir, 2008 (1).
3. Nguyen Van Tin. Dilu trj mat doan xuomg- khdp gia cd ngan chi d chi dudi bang phuong phap kit xuong hai 6 theo nguyen ly cua Ilizarov. Luan an tien sy y hgc, 1995, Hgc vien quan y
4. Nguyen Thj Thu Ha, Te bao gdc va kha nang sir dung te bao gdc trong dieu tri, Y hoc Viet nam, so dac bift, 2004, 302 (9), U 3-20.
5. Hernigou P, Poignard A, Beaujean F, Rouard H (2005), "Percutaneous autologous bone-marrow grafting for nonunions.
Influence of the number and concentration of progenitor cells", J^owe Joint Surg, 87A, pp
1430-1437.
6. Kitoh.H, Kltokoji.T, Tsuchiya. (2007) Transplantation of culture expanded bone marrow cells and platelet rich plasma in distraction osteogenesis of the long bones.
Bone, 40, pp 522-528.
