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Wxhؕ="6 3ZlZF~fu-ԙՍh9 `aMD/`u8kpHvbp.H#Iy[ )V+qki,N*k,a{]GK:oO#KtZզ|1o1NR7pI+ad6Y>f+WM:\YX/(ԁTHedCLe!ʿ^6B L Z2_]ѶY)SE ЈMP}*Twjf-Yҕo ΎcF8+:ELpDž $V)Q Ua?SE'pehp+0P*F hLh{Ye_C朥aN~ꀆHP؏T$هdbl$YFDTI\ZG䐰zoPnIV dYBͩ!ks|l2Rn6 MnBĊ]ծ7󽷬Y<+Yi+hei"skAf.xqQc,.~>_):P[|t l iG8AL5m:iw֒4vќ\Hcgvlmǖ<{2Eahdc(>zށ)S|_ZρH~, PK! ѐ'theme/theme/_rels/themeManager.xml.relsM 0wooӺ&݈Э5 6?$Q ,.aic21h:qm@RN;d`o7gK(M&$R(.1r'JЊT8V"AȻHu}|$b{P8g/]QAsم(#L[PK-![Content_Types].xmlPK-!֧6 +_rels/.relsPK-!kytheme/theme/themeManager.xmlPK-! 9\theme/theme/theme1.xmlPK-! ѐ' theme/theme/_rels/themeManager.xml.relsPK]   (  %   x`0e0e?Rectangle 2p  YHelicobacter Pylori ( <   x0 0e0e?Rectangle 3 @ P pHilary Suzawa January 2008     F?Text Box 4 m ( 2    zA??Hpylori1Picture 5Hpylori1ZP  zA??Hpylori2Picture 6Hpylori2 Y   zA??Hpylori3Picture 7Hpylori3  zA??Hpylori4Picture 8Hpylori4 .   zA??Hpylori5Picture 9Hpylori5    xA??HpyloriPicture 10Hpylori0H  0޽h ? ZXdbmo___PPT10u.>H+D=' n= @B +"U PH0 (      xП@ 0e0e?Rectangle 2 `}  ` M Nobel Prize      x@ 0e0e?Rectangle 3 `  } The 2005 Nobel Prize in Physiology or Medicine 3 October 2005 The Nobel Assembly at Karolinska Institutet has today decided to award The Nobel Prize in Physiology or Medicine for 2005 jointly to Barry J. Marshall and J. Robin Warren for their discovery of "the bacterium Helicobacter pylori and its role in gastritis and peptic ulcer disease" }0 Z2 Z0  9  $$((E+}EpH  0޽h ? ZXdbmo___PPT10u.p+D=' n= @B +"d _W@(  #   xA 0e0e?Rectangle 2 `}  Ġ WHelicobacter Pylori     xA 0e0e?Rectangle 3 ` / 4What is it? A spiral-shaped gram-negative bacterium Found in colonized gastric mucosa or adherent to the epithelial lining of the stomach Causes continuous gastric inflammation in virtually all infected persons Urease hydrolyzes urea into CO2 and ammonia and allows H. pylori to survive in acidic environment^ (   (   " 5H  0޽h ? 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ZXdbmo___PPT10.P-6+qZD|' lP= @B D7' = @BA?%,( < +O%,( < +Dn' =%(D' =%(D' =4@BBBB%(D' =1:Bvisible*o3>+B#style.visibility<*=N%(D' =+4 8?\CB#ppt_xBCB#ppt_xB*Y3>B ppt_x<*=ND' =+4 8?dCB1+#ppt_h/2BCB#ppt_yB*Y3>B ppt_y<*=N+" p(     x`ZE 0e0e?Rectangle 2 `}  6 QWhy do we care?  %   x^E 0e0e?Rectangle 3 `  \  YH. pylori is the cause of most cases of Peptic Ulcer Disease (PUD) Increases risk of both duodenal and gastric ulcers 95% of pt with duodenal ulcers and 80% of pt with gastric ulcers are infected Lifetime risk of peptic ulcer in pt with H. pylori is ~3%. H. pylori causes chronic gastritis H. pylori is a primary risk factor for gastric cancer (4th most common CA worldwide) Categorized as a group I carcinogen Increased risk if H. pylori infxn for >10 yrs. H. pylori increases risk of MALT lymphoma8C  x S *        $$(( ,,004488< <S    H  0޽h ? ZXdbmo___PPT10u.v+D=' n= @B +". )! (      x0{G 0e0e?Rectangle 2 `}  v O When to test?  ^   xPVE 0e0e?Rectangle 3 ` 00 American College of Gastroenterology Guidelines Previously in 1998 Revised in August 2007 and published in American Journal of Gastroenterology Diagnostic testing for H. pylori should only be performed if tx is intended0 Z` Z ZL Z0`     H  0޽h ? ZXdbmo___PPT10u.&+D=' n= @B +" $(  $ $  pG 0e0e?Title 1 `}   U2007 ACG Guidelines  ( $  G 0e0e?,Content Placeholder 2 `  BEstablished indications for eradication of H pylori include PUD: active PUD, a h/o documented peptic ulcer gastric mucosa-associated lymphoid tissue (MALT) lymphoma uninvestigated dyspepsia:  test and treat strategy \=   +$$ $  $ H  0޽h ? ZXdbmo___PPT10u.OM+D=' n= @B +" (M(  ( (  pH 0e0e?Title 1 `}   =Test and Treat Strategy   (  H 0e0e?,Content Placeholder 2P   &Uninvestigated dyspepsia (ie, unknown if pt has PUD) <55 years age No  alarm features Bleeding Anemia Early satiety Unexplained weight loss Progressive dysphagia Odynophagia Recurrent vomiting FMH GI CA Previous esophagogastric CA*WW H  0޽h ? ZXdbmo___PPT10u.PP+D=' n= @B +" ,(  , ,  ppI 0e0e?Title 1 `}   U2007 ACG Guidelines   ,  I 0e0e?,Content Placeholder 2 `   :Still controversy regarding whether to test for H pylori in functional dyspepsia a subset of patients with functional dyspepsia benefit from H pylori eradication gastroesophageal reflux disease (GERD) nonsteroidal anti-inflammatory drug (NSAID) use iron-deficiency anemia recent evidence suggests a link between H pylori infection and unexplained iron-deficiency anemia. risk factors for developing gastric cancerv< b 0Q  ^ H  0޽h ? ZXdbmo___PPT10u.O7K+D=' n= @B +" 03(  0' 0  x0I 0e0e?Rectangle 2 `}  0 [What tests are available?   0  xI 0e0e?Rectangle 3 ` ` |Non-invasive Diagnostic Tests Serologic tests Urea breath tests Stool antigen Endoscopic Tests Urease Histology Culture PCRV 1   1  }H  0޽h ? ZXdbmo___PPT10u.U+D=' = @B +"U PH4(  4 4  p`J 0e0e?Title 1 `}    4Gold Standard?  4  J 0e0e?,Content Placeholder 2 `   nAccording to 2007 ACG Guidelines  there is no single test that can be considered the gold standard for the diagnosis of H. pylori Most appropriate test depends on clinical situation&x 7 H  0޽h ? ZXdbmo___PPT10u.PA+D=' n= @B +" 8E(  8 8  xsJ 0e0e?Rectangle 2 `}   QSerologic Tests   8  xyJ 0e0e?Rectangle 3` `P u ELISA to detect IgG or IgA antibodies IgG Ab appear 2-3 weeks following infxn and slowly decrease after eradication Inexpensive and widely available Sensitivity and specificity Sensitivity 85% and specificity ~80% (from meta-analysis) Lower than in previous reports If pretest probability is low, a negative test excludes dz. If test is positive it may be a false + so recheck with a confirmatory testX PZ P PZ=L   H  0޽h ? ZXdbmo___PPT10u.?+D=' n= @B +"y tl<(  < <  pxK 0e0e?Title 1 `}  ` QSerologic Tests   <  K 0e0e?,Content Placeholder 2 `  QFalse + are more common in elderly and pt w/ cirrhosis Also, may underestimate infxn in elderly b/c lack of Ab response (false -) Not reliable in young children Poor PPV in low prevalence populations Limited use for F/U of therapy Takes a long time for serology to become negative In pt cured of infection, titers are at ~50% at 3 mthsJ Pi P' i   RH  0޽h ? ZXdbmo___PPT10u.O@Ą+D=' n= @B +" @!(  @ @  pLL 0e0e?Title 1 `}   T2007 ACG Guideline   @  RL 0e0e?,Content Placeholder 2 ` NP eFor populations with a low pretest probability of H pylori infection, the nonendoscopic urea breath and fecal antigen tests have a better positive predictive value than do antibody tests. Antibody testing identifies an immunologic reaction to the infection, whereas the urease tests and fecal antigen test identify the presence of active H pylori infection.Pf 2p    fH  0޽h ? ZXdbmo___PPT10u.Oz+D=' n= @B +" D"(  D D  xL 0e0e?Rectangle 2 `}   RUrea Breath Test   D  xL 0e0e?Rectangle 3 `  ` @Hydrolysis of urea CO2 and NH3. Measures labeled carbon. Sensitivity and specificity typically >95% in most studies False negatives with PPI, Abx, bismuth Off Abx and bismuth for >4 weeks Off PPI for > 2 weeks Used for both initial dx and F/U Wait 4 weeks before repeat for follow-up Z8 Z! Z) Z)c7  !) !H  0޽h ? ZXdbmo___PPT10u.Ф+D=' n= @B +"a \T H(  H H  p0aM 0e0e?Title 1 `}  F 6Urea Breath Test  H  @XM 0e0e?,Content Placeholder 2 ` G |Reliable in kids >6 yrs Best test in elderly population Most reliable non-endoscopic test to document eradication after tx"9 ZD}$ }H  0޽h ? ZXdbmo___PPT10u.P+D=' = @B +"  0L(  L  L  xM 0e0e?Rectangle 2 `}  Ͱ TStool Antigen Test  ( L  xM 0e0e?Rectangle 3 `P  \Sensitivity and specificity ~90% False positive (decreased specificity) in pt with acute UGI bleed False negative tests (decreased sensitivity) with abx, bismuth, PPI but not with H2 blocker Useful for documenting whether eradication has been successful Wait 4-8 weeks before repeat  H  0޽h ? ZXdbmo___PPT10u.+D=' M = @B +"  @P(  P P  xDN 0e0e?Rectangle 2 `}   K Endoscopy    P  xIN 0e0e?Rectangle 3 ` F` When to choose endoscopy Alarm sx such as anemia, GI bleeding, weight loss >50 yrs age 4 methods of testing: biopsy urease test, histology, bacterial culture, PCR According to AAFP article (2002) Steiner s stain for microscopic exam is gold standard According to ACG (1998), first choice is urease test on an antral biopsyF >  > DH  0޽h ? ZXdbmo___PPT10u.6+D=' n= @B +"l  g_PT(  T  T  xN 0e0e?Rectangle 2 `}   TBiopsy Urease Test   T  xN 0e0e?Rectangle 3` `  Sensitivity >90% and Specificity >95% Biopsy urease testing is less expensive than histology If biopsy urease test is negative, consider histology or serology Biopsy urease tests have decreased sensitivity in pt on PPI and in pt with recent or active bleeding False negatives: recent bleed, PPI, H2 blocker, Abx, bismuth Stop PPI and other meds that may interfere 4 wks prior to endoscopy Z H  0޽h ? ZXdbmo___PPT10u.+D=' Np= @B +"P KC`X(  X X  ppHP 0e0e?Title 1 `}  ( 82007 ACG Guideline  X  P 0e0e?,Content Placeholder 2 ` r QIn pt who have not been on PPI within 1-2 wk OR Abx or bismuth within 4 wk of EGD, the rapid urease test provides an accurate, inexpensive means of identifying H. pylori For pt who have been taking a PPI, Abx, or bismuth, EGD testing for H. pylori should include bx from the gastric body and antrum for histology +/- rapid urease testing:R D   Z RH  0޽h ? ZXdbmo___PPT10u.P+D=' n= @B +"e  `Xp\(  \ \  xP 0e0e?Rectangle 2 `}  x QCulture and PCR   \  xP 0e0e?Rectangle 3 `  Primary means by which Abx sensitivities can be determined Neither is widely available for clinical use Not routinely recommended Z H  0޽h ? ZXdbmo___PPT10u.0&S+D=' P= @B +"?  :2`(  `" `  x@Q 0e0e?Rectangle 2 `}  @ VWhy should we treat?  h `  xP$Q 0e0e?Rectangle 3" PK!Zf[Content_Types].xmlMO &2WR=cJ`F0iK`#̼vLw 9uSq:w`G ^i ½KI)c/ $oVjTMRc|}042ҥCƔM̏P~*ka/8^DkHbL8e i"K\XN\6rco4y@_;oPK!1_a _rels/.relsj0 ѽqCNo^K [ILcX&m߾0XFo;>0xM e`|X}đ I`߽N4aG2$RKIZ)4(M9`ctB{m:f@`3n|O,ܗr޾jxR0T ,0@}WBLǬ5vPK!Hbdrs/shapexml.xmlXn7}/ Z8um඀>.em%$W%=C.mI3Μruf](F')gR&c=ܝ\pЙPF˄ooav2 a҅,{eJ![}V:بPN!rͯaJR/}Xg;pEme 'd=ީ?&])dVsdrUJ\ȴ་ݕv%*FFdNa5ឳy:5E)XO˔):EؒQڿ5Ӆ(ePnFȈr~7gBmZ FBq{H)b>V@ p~hv)29s5R]Fd&% ѵKlN*b"=WԳYx"» r~ >0ոC$j) Ϫs۽C$,E~C/f!@eU50#K}n,{Y>U5./AMmRZ)֢S)MK0$UNe/&֘ygs))EXij˕jgTdP,ɯcq9В9^N55d3)'Gh8H;>$6Lj8h t* >P[*u/qnjJ|A*u/T:b" Q$#I_HRsd˕=|ޖ$¥{wnoXBEbZQZ/GGo{zm_gq~󱐽x!mZҴ#bÎ: o۪[ U;ig/ο쓱n0EZ!(S$@B+8<[SS/cR`mG28~%`nw9gj9(%2Z 66E t2A8 S9}C0u|fYKժ](/jc/x~2K89 bg(ע~.l[SP’]FˈJs*`ZR9?1I)h@t[aVFENX~L2<. S(4Wh]XCT %Xv R(݊Jb(;@d5} kN m `D8󮁁 )y$/?@Ƙ =D_bnt/bnCS;qkzz_[z}ҙPK!Vdrs/downrev.xmlDN@EM͘& Z>`m;[wW(}ɹ9`:q$[ QZ|Ycgrq}5\XZD 4!jȠٞ8uC<]-SN'Ƀ4r\huCWcq5fs27no D!?c.?zѱ%1õz>Sbm PK-!Zf[Content_Types].xmlPK-!1_a /_rels/.relsPK-!Hb*drs/shapexml.xmlPK-!Vdrs/downrev.xmlPK ` V`~v___PPT9XP <Eradication Results in ulcer healing Decreases risk of ulcer recurrence more than a 30% reduction in the risk for recurrent ulcer at 1 year Reduces risk for serious ulcer complications (perforation or bleeding) Leads to regression of MALT lymphoma Eradication of H pylori is less robust in reducing rates of dyspepsia and gastric cancer.j  Z ZZ " Z 1O{ C SH  0޽h ? ZXdbmo___PPT10u.@c+D=' = @B +" df(  d d  xPFR 0e0e?Rectangle 2 `}   K Treatment    d  x0Q 0e0e?Rectangle 3 `  CH. pylori regimens should have cure rates of at least 80% (desirable) Dual therapy (PPI + one abx) regimens have eradication rates of 60-85% and are not recommended Triple therapy: combination of antibiotics and PPI or H2 blocker or bismuth" Z  H  0޽h ? ZXdbmo___PPT10u.Y+D=' n= @B +"0 +#h(  h% h  xS 0e0e?Rectangle 2 `}  0 YTriple Therapy Regimens  V h  xS 0e0e?Rectangle 3 `  Previously 3 regimens consistently eradicated H. pylori with rates >90% now may be dropping to ~75-80% b/c of clarithromycin resistance First Line (ACG and Maastricht Consensus European) PPI (lansoprazole 30 mg po BID), amoxicillin 1 gram po BID, clarithromycin 500 mg po BID x 14 days (Prevpac) Above but change amoxicillin to metronidazole 500 mg po BID for PCN allergic Alternative: PPI or H2, bismuth 525 mg po QID, 2 antibiotics (metronidazole 500 mg po QID, tetracycline 500 mg po QID) x10-14 daysf Z.   t H  0޽h ? ZXdbmo___PPT10u.+D=' n= @B +" l(  l# l  x0tT 0e0e?Rectangle 2 `}  F0 WDuration of Treatment   l  x\U 0e0e?Rectangle 3 ` ` Course of 7-14 days 7-day course more common in Europe 10-14-day course recommended in US Triple therapy: 14 days Quadruple therapy: 10-14 days*\ 8 \8 H  0޽h ? ZXdbmo___PPT10u.0W+D=' TQ= @B +"2 -%p(  p p  pU 0e0e?Title 1 `}  ^ N New Regimens   k p  PU 0e0e?,Content Placeholder 2 `  Trial of quadruple therapy for non-responsive cases (ie, salvage) Regimens with levofloxacin instead of clarithromycin Sequential therapy 5 days of one regimen (PPI + amoxicillin) followed by 5 days of a second regimen (PPI, clarithromycin, tinidazole) Lactoferrin and Probiotics@ s  s H  0޽h ? ZXdbmo___PPT10u.O _+D=' n= @B +" t(  t  t  pU 0e0e?Title 1 `}   \Lactoferrin and Probiotics  H t   V 0e0e?,Content Placeholder 2 `  b New studies adding these agents to triple therapy De Bortoli et al in Italy 206 patients Esomeprazole 20 mg, amoxicillin 1000 mg, and clarithromycin 500 mg, all twice daily for 7 days +/- bovine lactoferrin 200 mg and probiotic Probinul (Cadigroup) tablets twice daily(  ! H  0޽h ? ZXdbmo___PPT10u.O$+D=' n= @B +" x (  x  x  poV 0e0e?Title 1 `}  g \Lactoferrin and Probiotics   x  uV 0e0e?,Content Placeholder 2 ` o fMain study outcome was negative 13C-urea breath testing at 8 wks after completion Eradication of H pylori in 88.6% of intervention group vs. 72.5% of control group. Rates of adverse events were 9.5% in the intervention group vs 40.6% in the control group. Side effects of nausea, diarrhea, glossitis, and abdominal pain were more common in the control group.F g a g   gH  0޽h ? ZXdbmo___PPT10u.OPCg+D=' = @B +"" |      !"#$%&'()*+,-./0123456789=>?@ABCDEFGHIJKLMNOPQRSTUVWXYZ[\]^_`abcdefghijklmnopqrstuvwxyz{|}~(  | |  xV 0e0e?Rectangle 2 `}  ` SPossible Outcomes  N |  x@V 0e0e?Rectangle 3 ` p Eradication Pt is treated but H. pylori remains positive (Failure of initial treatment) Pt is treated and follow-up tests are initially negative at 4 weeks (Eradication) but then become positive later (Recurrence) Recurrence can be caused by either Recrudescence or Re-infection> A  A  H  0޽h ? ZXdbmo___PPT10u.etGC+D=' n= @B +": 5-(     pJW 0e0e?Title 1 `}  I T2007 ACG Guideline  m   POW 0e0e?,Content Placeholder 2 ` J To confirm eradication of H pylori infection, testing should be performed in patients with PUD persistent dyspeptic symptoms following the test-and-treat strategy H pylori-associated MALT lymphoma status post resection of early gastric cancerfN  , DH H  0޽h ? ZXdbmo___PPT10u.O0F+D=' n= @B +"t og(     xW 0e0e?Rectangle 2 ``   ISummary     x@W 0e0e?Rectangle 3  `    rH. pylori infection increases risk of PUD, chronic gastritis, gastric CA, and MALT lymphoma Check for H. pylori in pt with PUD, MALT lymphoma, undifferentiated dyspepsia Serology less reliable test; urea breath test and fecal antigen testing preferred Consider EGD for alarm sx or age >50 yrs Triple therapy for treatment has decreasing efficacy now ~75-80% Test for eradication if PUD, persistent sx, MALT lymphoma, s/p gastric CA resection> Z ] K   H  0޽h ? ZXdbmo___PPT10u.fY+D=' n= @B +"   (     x UX 0e0e?Rectangle 2 `}  9` N Bibliography   >   xpW 0e0e?Rectangle 3 `P U r`Chey WD, Wong BC et al. American College of Gastroenterology Guideline on the Management of Helicobacter pylori Infection. Am J Gastroenterol 2007 Aug; 102(8):1808-25. De Bortoli N, Leonardi G, Ciancia E, et al. Helicobacter pylori Eradication: A Randomized Prospective Study of Triple Therapy Versus Triple Therapy Plus Lactoferrin and Probiotics. Am J Gastroenterol. 2007; 102: 951-956. Fisschbach L and Evans E. Meta-analysis: The Effect of Antibiotic Resistance Status on the Efficacy of Triple and Quadruple First-line Therapies for Helicobacter pylori. Aliment Pharmacol Ther 2007; 26(3): 343-357.  Z\2   6v  $$((,,0044 88"|,H  0޽h ? ZXdbmo___PPT10u.Vpᵵ+D=' n= @B +" 0(     pD[ 0e0e?Title 1 `}  , N Bibliography   W   Z 0e0e?,Content Placeholder 2 ` q qGisbert J. The Recurrence of Helicobacter pylori Infection: Incidence and Variables Influencing It. A Critical Review. Am J Gastroenterol 2005; 100: 2083-2099. Meurer L et al. Management of Helicobacter pylori Infection. American Family Physician 2002; 65 (7): 1327-1336. Salles N and Megraud F. Current Management of Helicobacter pylori Infections in the Elderly. Expert Rev Anti Infect Ther. 2007; 5(5): 845-856. Suerbaum S and Michetti P. 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PrevalenceWhy do we care?When to test?2007 ACG GuidelinesTest and Treat Strategy2007 ACG GuidelinesWhat tests are available?Gold Standard?Serologic TestsSerologic Tests2007 ACG GuidelineUrea Breath TestUrea Breath TestStool Antigen Test EndoscopyBiopsy Urease Test2007 ACG GuidelineCulture and PCRWhy should we treat? TreatmentTriple Therapy RegimensDuration of Treatment New RegimensLactoferrin and ProbioticsLactoferrin and ProbioticsPossible Outcomes2007 ACG GuidelineSummary Bibliography Bibliography  Fonts UsedDesign Template Slide Titles"$ 8@ _PID_HLINKS'A http://www.mednobel.ki.se/http://www.mednobel.ki.se/*_8BDAnoop Agrawal UserAnoop Agrawal User