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Evaluation of the Accuracy of Diagnostic Tests for
,2ῌ - ῌ P+,1ῌP+-- *Med. Bull. Fukuoka Univ.6 ,2*-6, +,1῎+--, ,**+ Evaluation of the Accuracy of Diagnostic Tests for Helicobacter Pylori Infection Hirokatsu N>H=>BJG6, Mitsuru S:D, Mitsuo O@696, Motonobu K6C96, Motoko K6L6H=>B6 and Kazuo T6BJG6 Department of The First Internal Medicine, School of Medicine, Fukuoka University Abstract : The aim of this study was to evaluate the accuracy of five diagnostic tests for H. pylori. Each gastric specimen underwent PCR, culture and histological examinations. Serology and +-C῎UBT analyses were also performed before or after endoscopy. The sensitivity and specificity were as follows ; for PCR : 3240 and +**, for culture : 3*4- and +**, for the histological examination : 204+ and +**, for +C῎UBT : 3-4+ and 3/42, and for serology : 3240 and 114+. These results suggest that a combination of the above diagnostic tests would likely improve the accuracy of detecting H. pylori infection. Key words : Helicobacter pylori, diagnostic test, PCR, +- CῌUBT Helicobacter pylori ῍῍PCR +- C῎UBT ῍῍ H. pylori !"# / $%&'() *PCR ) +,) -./01'( +-C῎UBT 2345)6 &78 9:;<='>?@A +,*B&CD EFGHIJKLM? PCR ) +,) -./01'(&@NOPQRSTU5VRWXYZ - [\9]'? @A EFGHIJ&P^?_`a +-C῎UBT STU2345)&@N&b2KMc@A Y'(&d8ῌef8`ghih PCR ) j 3240ῌ+** +,) j 3*4-ῌ+** -./0 1'( j 204+ῌ+** +-C῎UBT j 3-4+ῌ3/42 2345) j 3240ῌ114+klc @A H. pylori mnopa&qrKm:;st?@uv 2345)&ef8`224+ Ew? @A 2345)`mna&qrKxN#yef8z{^|_ mna& H. pylori &}~ S :;`kl#yXh@A mnopK1y?@ H. pylori d &}~ `+,)z kl#z }~&78K"@N'(y&/vzkl#yzh@A Helicobacter pylori, diagnostic test, PCR, 2+.῎*+2* 1῎./῎+ +- CῌUBT ῍ 128 ῍ Table + ῍ ῌ +32- Warren Marshall+ Helicobacter pylori H. pylori H. pylori H. pylori MALT ! "#$%&'( ) H. pylori *+, -. MALT !"#$/0123,῎/ 4 H. pylori 56789:, ;89 Polymerase chain reaction PCR %<=0>+- C῎Urea Breath Test +-C῎UBT .? @!%<=0 4">: A89#$5 :45;890 gold standard %BC&D: Thijs )0 5 PCR 0E1'(890FGHI H. pylori Endoscopic diagnosis and the incidence of H. pylori infection in +,* study patients Diagnosis Normal Gastritis Duodenitis Gastro῎duodenitis Peptic ulcer Gastric ulcer ¸ Duodenal ulcer ¸ Combind ulcer ¸ Malignant tumor Gastric cancer Malignant lymphoma Others All patients n H. pylori positive ++ .1 1 ,14- /-4, 0041 ,240 +2 +3 , 1142 1243 +** / , 0 +** /*4* /*4* +,* 0*4* ¸ Includes ulcer scar. 0 A89#$08) 4 *+J4 5 PCR 0E1 H. pylori #$0 KL8) 35MNODF) 4 21 Dtm PCR 5 Agglutination Partition method Sepa- P75 H. pylori , / 6-89 PCR geneῌ : wxyE *+ 0F4 DNA 0Gzt ;89 Clayton )1 ureA {H|0}b~ c +- C῎UBT ? @! # $Q4%B8) b HPU῎+ HPU῎, 0F4m DNA polymerase 5 Ampli Taqῌ #b" b USA 0 ῏ ῎ F4 3. +*rc"bt IJ 3. +331++RS)+333+*ROD.T/;U0C + r b!" ., 1, + r KLM + r 0-/m4 t1, +* VJ4W1X<=890YZ([ in- ra"b"0l b formed consent 2) +,*3([0,\ b5 PJ,*** #b" b USA 0F <=54]++3 -33 .13 PCR NOP5 , b~DQR ^5_6 - 3 ^5_6 1 3 / 3 ` t ¡¢S0m4 .++bp £"¢ !"#$ , 3 78 + 3 a!bc . 3 ^5_ 1) s0T Figure + 6a!bc + 3D: Table + 9d:eSD 5 8 ! 5 8 9 m H O D Hanks ¤ .3e+1f +3g2,f D;0-3 h/13D: GIBCO, BRL, USA + g - *rUV ¥¦ H. pylori *+i<jk:([5 0 3 jk §¨b¥¦§© t Skirrow WX 4([5++.3D: Y "b}b ASTEC, BL῎+0**, * + 0F4 -1 Zª«¬ / [ +*5 ῐ ῑ \[ 2/][ D / g 1 *r ®b¯ ^ S°Db±²³ ´}b± W1X<=lmn PCR ;891=>1/?Jo!@1/?S) A7 - pqQA8 ²³ µ¶b±²³TD:s0 H. pylori T 2 C῎UBT 5<=89=*: ;895· ¨S H. pylori +! 45<=89 + nr=s 589t , nr Jo H. pylori _ZAP1) s0T +- m ? @!uBC1v?5 C῎UBT +- ;89`89s=>1/ Diagnosis of H. pylori E«¬ῌ¡Q ῎ 129 ῎ n]urs) H. pylori uSv w H. pylori n]xy z{y |}mV u|}mV ++- )~ wn]y)@ C῏UBT !"#!$%&'()*+ C ,-./ +**mg )0 +**ml !123456 7! 0809:);<!=>56 34?,*< ' ( ) * + ' ( +- EABCA῏G F GHIJKLMN OPQ RS ,*< 1,/+,* E0*4*Q H. pylori .2/+,* TUV ED+-CQ ,4/WXY)3Q Z[\] enzyme C @)AB<CD linked E.*4*Q H. pylori u H. pylori x y 134/ E-+/-3Q +** immuno῏sorbent assay EJ^_`a῍ F GHIJKLMNQ !$\ H. /* /-4, ;0041 pylori IgG \)RS ELISA value ,4-XY ;,240 ,14, ETable b)+*Q +Q Thijs 0Q ]!cde PCR ] fg] hij klmn C῏UBT Z[\] , opXY ETable , -Q +- n]qrs) H. pylori . tXY PCR ] H. pylori 1+/1, Exy 3240 3/ CI 3/43῏+**Q H. pylori u .2/.2u Ez{y+** CI 3,43῏+**Q + u ¡ . tn ] fg]xyῌz{y ECIQ ¢£3*4- E2-4/῏ 314+Q +** E3,43῏+**Q u 1 0 ¡ . n¤$ + PCR ] C῏UBT Z[\] +- h i j k l m n x y ῌ z { y ECIQ 314, E3-4.῏+**Q +** E3,43῏+**Q u , + ¡ . n¤$ + PCR ] C῏UBT Z[\] +- ETable .Q ¥¦q + §hi¨©zShi¨r sxyῌz{y¢£314, +**204+ +** Figure + +- Detection of H. pylori DNA Elane +, ,, .Q Table , C῏UBT x y ῌ z { y ECIQ 3-4+ E214,῏ 334*Q 3/42 E3*῏+**Q u Comparison of detection of H. pylori among diagnostic tests EQ Sensitivity PCR Culture Histological examination +C῏urea breath test Serological test 3240 3*4314, 3-4+ 3240 Specificity E3/43῏+**Q +** E2-4/῏314+Q +** E3-4.῏+**Q +** E214,῏334*Q 3/42 E3/43῏+**Q 114+ E3,43῏+**Q E3,43῏+**Q E3,43῏+**Q E3*4+῏+**Q E0/4,῏234*Q PPV +** +** +** 314+ 2040 PPVªpositive predictive value ; NPVªnegative predictive value E Q 3/ Confidence Intervals NPV E3.43῏+**Q 324* E3.4+῏+**Q E3.4/῏+**Q 214- E124/῏304+Q E3.4,῏+**Q 304* E3*40῏+**Q E3-4+῏+**Q 3*4, E2,4*῏324.Q E134,῏3.4*Q 314- E3,4+῏+**Q ῍ 130 ῍ / . , H. pylori 0 Table / ῌ CI 3240 3/43῎ . 0 !"#$%& +** 114+ 0/4,῎234* + ++ '( 114+()224+ *+# Table - PCR Cul HP Result of H. pylori infection in +,* study patients positive negative His UBT Ser n H. pylori ,-.*/012345 gold standard 6#789:5 8 # ² ² ² ² ² ³ ² ² ² ² ² ³ ² ³ ² ² ³ ² ² ² ³ ² ² ² ³ ² ² ² ² ³ ² ² ² ² ² /1 + + / 0 + + .14/ *42 *42 .4, /4* *42 *42 ³ ³ ³ ³ ³ ³ ³ ³ ³ ³ ² ³ ² ³ ³ ++ , -/ 34, +41 ,34, lmnXmS+/+0 $op qr#78 PCR +,* +** 8 d PCR }] H. pylori -.~ Total (# H. pylori ;<=>#$?*@8$ '% AB9*;<C8D6++ EF G HIJKC8D6 LM&E;<C8NO HEPQ'7D6+, ()D , RS TUSVWXYEZ8[\ 8 D] ^I 2_`@a H. pylori , -.C8D6 6C8b0+-+. $ c defghYijk s<tu9:v5*wxp7'7 Crayton1 )by z]{|76xp7 {*7*#b'7] PCR HP : H. pylori, Cul : culture, His : histological examination, Ser : serological test, ² : positive, ³ : negative } / H. pylori -.~*7o-. \{*# PCR 3240 +** c Table . # / G$p H. pylori Accuracy of Histological detection of H. pylori ῌ ῍ Sensitive Spcificity 314, 3-4.῎+** 204+ 124+῎3.4+ +** 3,43῎+** +** 3,43῎+** \ #7 PCR *|7{ b01+1+2 69#7 + _ # D6# PCR F0xp*%7 DNA ; <'+3 )p PCR * ¡ 8 ῌ : One experienced pathologist examined all matearials ῍ : Some pathologists examined matearials 3/ Confidence Intervals Table / ]*¢£¤0E¥*¦(*§¨#H$xp c+3,* PCR ©ª«S¬®Y¯°SEZ8 [\ 8 #(#') H. pylori !H± *fc Comparison of detection of H. pylori among diagnostic tests exclude eradicated patients Sensitivity PCR Culture Histological examination +C῎urea breath test Serological test 3240 3*4314, 3-4+ 3240 Specificity 3/43῎+** +** 2-4/῎314+ +** 3-4.῎+** +** 214,῎334* 3/4, 3/43῎+** 224+ 3+4,῎+** 3+4,῎+** 3+4,῎+** 2241῎+** 124-῎3143 PPV +** +** +** 314+ 3-4, PPV´positive predictive value ; NPV´negative predictive value 3/Confidence Intervals NPV 3.43῎+** 3141 3-4,῎+** 3.4/῎+** 2/41 1/43῎3/4/ 3.43῎+** 3/4/ 234.῎+** 3-4+῎+** 2243 1341῎324+ 214/῎3243 314- 3,4+῎+** Diagnosis of H. pylori "z{ῌ* H. pylori coccoid form ,, PCR H. pylori ῍ 131 ῍ BL# b=Jc d67( U1N H. pylori &[e\5NbUf5 1 PCR ! "RFLP CD$R=J2<-.-/ SP/ # H. pylori $%,/,0 & CD$%E + ZgR %.*M ' ()*+,-./0% PId5B)O%8-. CD$R 1 2342567( hi j-Y#Z 89:; <5 {!+/+0 %k5 UVW 25& ,-,. H. pylori !=">&?@A "3240M Id5]114+M / .\l 5B # H. pylori CD$% %d1Q SP Q++./R 0 /CD E&F'G(H,1 8 CD$IJ $I?X H. pylori &#=J BK L & 25`aNb K CD$I?X 0 mI 3*4-M Thijs N)O0 P02</1Q C50U 5]114+M1N224+Mn *)O+2 + Q Xia N,2 CD$R ¡ "Table / *+,8 H. pylori ! ST,2</UI)O5 =I¢=">D$I?X,omC -VW CD$I?X./IC50 fb0 U1N £ / /%SP %Y#Z1234[.\&ῌ5]6 /Q1%b/5 1 K,o=" /1QU# H. pylori CD$7.\ >IT51 o Q &¤<¥¦ 89^_`aNb/1Q 1 2[oY#Zpd§,o b=JST" PCR &&#:+*M;b5 kU+* -VW ST Q + /* U# ST/% H. pylori .\¨P ©ª/%Z U1N&¤ c<5defb gR <¥¦q«`aNb CD$=h>5'G(?ijC@A CD$IF H. pylori & "k fNl/Q<UBCf r ^I?8*.\3 b ¬® Udefb C 1234[.\m34 nD12[opAH 0,3 qrVW stuDI5 v!wx!y z{ %E./ H. pylori 58 1234[.\ *.\<N¨S T"k25 K H. pylori CRp IE|F GHIJI , }~1N".I ¯I¬VW j&#%js25f JQ K12[o&204+M b5,2 H. pylori &^2<1 Q pA + LMN12 c dX/t2C -VW / &314,M Q UU1N%123 .\u°1N 4[.\12[opAHU aNb C῎UBT %h5` +- defb +- C῎UBT *)O-*῎-- O& "3-4+Mῌ ῌ ῍ 5] "3/42M %21Q SPId , / *.\QT Q C῎UBT RS H. pylori ±7(² r :/v~w~ #SPI"k ¬Nb PCR &ῌ5]%%2< H. 8 @'TRRI0UVU pylori & 9 /5 fb5 UBT PCR ³5 ^2< WX +- U , ./RUV 0 -*῎-- SP"k`aNb C῎ +- C῎UBT WX U# H. pylori & /.\ Y5Z[\ ].\ H. pylori 'G(.´/8 C +- ^%2< QJ _I`U1N H. pylori Ca -*῎-- 1 C῎UBT 67(255 +- D$Iµxyb H. pylori &I ¶-K.\I5 ¨· ῍ 132 ῍ ῎ ῍ ῏ ῌ + Warren J. R, Marshall B. 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