JHepatobiliaryPancreatSci(2013)20:1–7 DOI10.1007/s00534-012-0566-y GUIDELINE TG13: Updated Tokyo Guidelines for acute cholangitis and acute cholecystitis TG13: Updated Tokyo Guidelines for the management of acute cholangitis and cholecystitis TadahiroTakada • StevenM.Strasberg • JosephS.Solomkin • HenryA.Pitt • HarumiGomi • MasahiroYoshida • Toshihiko Mayumi • Fumihiko Miura • Dirk J. Gouma • O. James Garden • Markus W. Bu¨chler • Seiki Kiriyama • Masamichi Yokoe • Yasutoshi Kimura • Toshio Tsuyuguchi • Takao Itoi • Toshifumi Gabata • Ryota Higuchi • Kohji Okamoto • Jiro Hata • Atsuhiko Murata • Shinya Kusachi • John A. Windsor • Avinash N. Supe • SungGyu Lee • Xiao-Ping Chen • Yuichi Yamashita • Koichi Hirata • Kazuo Inui • Yoshinobu Sumiyama Publishedonline:11January2013 (cid:2)JapaneseSocietyofHepato-Biliary-PancreaticSurgeryandSpringer2012 Abstract In 2007, the Tokyo Guidelines for the man- presence of divergence between severity assessment and agementofacutecholangitisandcholecystitis(TG07)were clinical judgment for acute cholangitis. In June 2010, we firstpublishedintheJournalofHepato-Biliary-Pancreatic set up the Tokyo Guidelines Revision Committee for the Surgery. The fundamental policy of TG07 was to achieve revision of TG07 (TGRC) and started the validation of the objectives of TG07 through the development of con- TG07. We also set up new diagnostic criteria and severity sensusamongspecialistsinthisfieldthroughouttheworld. assessment criteria by retrospectively analyzing cases of Consideringsuchasituation,validationandfeedbackfrom acutecholangitisandcholecystitis,includingcasesofnon- the clinicians’ viewpoints were indispensable. What had inflammatory biliary disease, collected from multiple been pointed out from clinical practice was the low diag- institutions. TGRC held meetings a total of 35 times as nostic sensitivity of TG07 for acute cholangitis and the well as international email exchanges with co-authors abroad.OnJune9andSeptember6,2011,andonApril11, T.Takada(&)(cid:2)F.Miura D.J.Gouma DepartmentofSurgery,TeikyoUniversitySchoolofMedicine, DepartmentofSurgery,AcademicMedicalCenter,Amsterdam, 2-11-1Kaga,Itabashi-ku,Tokyo173-8605,Japan TheNetherlands e-mail:[email protected] O.J.Garden S.M.Strasberg ClinicalSurgery,TheUniversityofEdinburgh,Edinburgh,UK SectionofHepatobiliaryandPancreaticSurgery,Washington UniversityinSaintLouisSchoolofMedicine,SaintLouis, M.W.Bu¨chler MO,USA DepartmentofSurgery,UniversityofHeidelberg, Heidelberg,Germany J.S.Solomkin DepartmentofSurgery,UniversityofCincinnatiCollegeof S.Kiriyama Medicine,Cincinnati,OH,USA DepartmentofGastroenterology,OgakiMunicipalHospital, Ogaki,Japan H.A.Pitt DepartmentofSurgery,IndianaUniversitySchoolofMedicine, M.Yokoe Indianapolis,IN,USA GeneralInternalMedicine,NagoyaDainiRedCrossHospital, Nagoya,Japan H.Gomi CenterforClinicalInfectiousDiseases,JichiMedicalUniversity, Y.Kimura Tochigi,Japan DepartmentofSurgicalOncologyandGastroenterological Surgery,SapporoMedicalUniversitySchoolofMedicine, M.Yoshida Sapporo,Japan ClinicalResearchCenterKakenHospital,International UniversityofHealthandWelfare,Ichikawa,Japan T.Tsuyuguchi DepartmentofMedicineandClinicalOncology,Graduate T.Mayumi SchoolofMedicineChibaUniversity,Chiba,Japan DepartmentofEmergencyandCriticalCareMedicine, IchinomiyaMunicipalHospital,Ichinomiya,Japan 123 2 JHepatobiliaryPancreatSci(2013)20:1–7 2012, weheldthreeInternationalMeetingsfortheClinical Keywords Acute cholangitis (cid:2) Acute cholecystitis (cid:2) Assessment and Revision of Tokyo Guidelines. Through Charcot’s triad (cid:2) Biliary infection (cid:2) GRADE thesemeetings,thefinaldraftoftheupdatedTokyoGuide- lines(TG13)waspreparedonthebasisoftheevidencefrom Background before Tokyo Guidelines 2007 retrospective multi-center analyses. To be specific, discus- siontookplaceinvolvingtherevisednewdiagnosticcriteria, Acute cholangitis and cholecystitis require appropriate andthenewseverityassessmentcriteria,newflowchartsof treatmentinthe acute phase. Severeacute cholangitis may themanagementofacutecholangitisandcholecystitis,rec- result in early death if no appropriate medical care is ommendedmedicalcareforwhich newevidencehadbeen provided in the acute phase. Before the publication of the added, new recommendations for gallbladder drainage and TokyoGuidelinesforthemanagementofacutecholangitis antimicrobialtherapy,andtheroleofsurgicalintervention. andcholecystitis(TG07)inJanuary2007[1],therewereno Managementbundlesforacutecholangitisandcholecystitis practical guidelines throughout the world primarily tar- wereintroducedforeffectivedisseminationwiththelevelof geting acute cholangitis and cholecystitis. evidence and the grade of recommendations. GRADE sys- TG07 had substantial influence on medical care for temswereutilizedtoprovidethelevelofevidenceandthe biliary infections throughout the world in that they clearly grade of recommendations. TG13 improved the diagnostic defined the diagnostic criteria and severity assessment sensitivity for acute cholangitis and cholecystitis, and pre- criteria for acute cholangitis and cholecystitis, the defini- sented criteria with extremely low false positive rates tion of which had until then been ambiguous. TG07 has adapted for clinical practice. Furthermore, severity assess- providedinternationalstandardsfordiagnosticandseverity mentcriteriaadaptedforclinicaluse,flowcharts,andmany assessment criteria. This has enabled the comparison and new diagnostic and therapeutic modalities were presented. integration of multiple studies (i.e., meta-analysis or sys- The bundles for the management of acute cholangitis and tematic reviews). cholecystitisarepresentedinaseparatesectioninTG13. TG07 was initially developed through the following Free full-text articles anda mobile application ofTG13 processes. An international consensus meeting was held in areavailableviahttp://www.jshbps.jp/en/guideline/tg13.html. Tokyo on April 1 and 2, 2006. A total of 29 experts from T.Itoi A.N.Supe DepartmentofGastroenterologyandHepatology,Tokyo DepartmentofSurgicalGastroenterology,SethGSMedical MedicalUniversity,Tokyo,Japan CollegeandKEMHospital,Mumbai,India T.Gabata S.Lee DepartmentofRadiology,KanazawaUniversityGraduate HepatoBiliarySurgeryandLiverTransplantation,AsanMedical SchoolofMedicalScience,Kanazawa,Japan Center,UlsanUniversity,Seoul,Korea R.Higuchi X.-P.Chen DepartmentofSurgery,InstituteofGastroenterology,Tokyo DepartmentofSurgery,HepaticSurgeryCentre, Women’sMedicalUniversity,Tokyo,Japan TongjiHospital,TongiMedicalCollege, HuazhongUniverstyofScience&Technology, K.Okamoto Wuhan,China DepartmentofSurgery,KitakyushuMunicipalYahataHospital, Kitakyushu,Japan Y.Yamashita DepartmentofGastroenterologicalSurgery,FukuokaUniversity J.Hata SchoolofMedicine,Fukuoka,Japan DepartmentofEndoscopyandUltrasound,KawasakiMedical School,Okayama,Japan K.Hirata DepartmentofInternalMedicine,SecondTeachingHospital, A.Murata FujitaHealthUniversitySchoolofMedicine,Nagoya,Aichi, DepartmentofPreventiveMedicineandCommunityHealth, Japan SchoolofMedicine,UniversityofOccupationaland EnvironmentalHealth,Kitakyushu,Japan K.Inui DepartmentofSurgeryI,SapporoMedicalUniversityHospital, S.Kusachi Sapporo,Hokkaido,Japan DepartmentofSurgery,TohoUniversityMedicalCenterOhashi Hospital,Tokyo,Japan Y.Sumiyama TohoUniversitySchoolofMedicine,Tokyo,Japan J.A.Windsor DepartmentofSurgery,TheUniversityofAuckland,Auckland, NewZealand 123 JHepatobiliaryPancreatSci(2013)20:1–7 3 22countriesandJapaneseexpertsinthisfieldattended the Table1 Summary of citations of TG07 (from January 2007 to meeting. To obtain consensus, a voting system was used. December2011) As the final product of this international consensus meet- NumberofpapersinTG07citedatleastonce 14 ing, TG07 [2] was published in 2007. Totalnumberoftimesofcitation 209 Theprocessofpreparationwasbynomeanseasy.TG07 NumberofarticlescitingpapersinTG07 122 was the world’s first clinical practice guidelines on the NumberofjournalspublishingarticlescitingpapersinTG07 77 management of acute cholangitis and cholecystitis. There were many obstacles to overcome. The preparation of TG07 started according to the principle of evidence-based medicine. However, due to the absence of diagnostic cri- teria and severity assessment criteria, studies available at that time were very few in number, and even if there was extracted evidence, the criteria lacked unity and the con- tents were often ambiguous. Furthermore, items to be discussed included diagnostic methods and clinical deci- sion-making such as the selection of antimicrobial agents andtheirbiliarypenetration,therouteandtimingofbiliary drainage, the timing of surgical intervention, and health- care-associated (e.g., postoperative) cholangitis and cho- lecystitis. It took an enormously long time to cover the Fig.1 AnnualnumberofcitationsofTG07 overall guidelines. 5.2 3.9 Citation analysis 2007–2011 of TG07 6.5 33.8 11.7 TG07 has been cited widely since its publication. The numberofpaperscitingTG07[1,3–5]hasbeenincreasing 14.3 everyyear[6]andhasreachedapproximately209treatises. Those treatises have been cited in textbooks of surgery, internal medicine, and guidelines of abdominal infections [7–9]. The significance of this is that TG07 has had sub- stantial influence on medical education and has become Fig.2 Categoriesofthejournalspublishingarticlescitingpapersin disseminated throughout the world as a global standard. TG07(n=77) The results of the survey that examined the number of citationsofTG07 untilDecember 2011 showthat the total 1.6 number of citations of TG07 was 209 in 2009 (Table 1). 1.6 The number of citations occurring each year since 2007 is 11.5 presented in Fig. 1. 32.8 23.8 The number of journals that cited TG07 was 77. Figure 2providesabreakdownofthefieldsofthejournals that cited TG07. 28.7 Therewere112treatisesthathadbeencitedfromTG07. Figure 3 provides a breakdown of the residential areas of theauthors.Table 2showsthetypesofarticleswhichcited TG07. Of the 76 original treatises, 20 (26.3 %) were cited Fig.3 Geographical origin of authors citing papers in TG07 (n=122) in method sections (Fig. 4). The citation of original trea- tises inmethod sectionshas been onarapidincreasesince 2011(Fig. 5).Ofthetreatisescitedinthemethodsections, Need for revision of TG07 studies had been conducted in 17 titles concerning diag- nostic criteria and/or severity assessment criteria (Fig. 4). 1. The development of evidence-based guidelines, clinical In summary, TG07 has been cited in journals in various practice and assessment fields throughout the world, although only 5 years’ cita- ThepublicationofTG07enabledthepresentationofthe tions were totaled. firstinternationaldiagnosticcriteriaandseverityassessment 123 4 JHepatobiliaryPancreatSci(2013)20:1–7 Table2 TypesofarticlescitingTG07 Develop Clinical Guidelines Typesofarticles No.ofarticles Evidence and consensus based Originalarticle 76(62.3%) Review 20(16.4%) Publication and assessment distribution Casereport 11(9.0%) Guideline 7(5.7%) Others 8(6.6%) Use Guidelines Total 122 Fig.6 Evidence–practicecycle In 17 articles, patients were diagnosed according to the diagnostic criteria and severity assessment of TG. and therapeutic methods. Therefore clinical practice guidelinesrequireregularupdateandrevision[12].Inview ofthesecircumstances,anevidence-basedrevisionprocess is also required for TG07. After its publication, an appraisal from clinicians has been taking place concerning dissemination/useand the results are being made good use of for future revision (Fig. 6). 2. Validity of TG07 GiventhecriticalappraisalofTG07,thereareproblems in applying it in clinical settings. First, the sensitivity of Fig.4 Sectionwherecitedinoriginalarticles(n=76) acute cholangitis is low. Second, there are impractical aspects in the severity assessment criteria for moderate acute cholangitis such as deciding the timing of biliary drainage. There were discordances between clinical judgement by clinicians and the level of severity utilizing TG07 severity assessment criteria. Process of the development of Tokyo Guidelines 2013 (TG13) 1. The First International Meeting for the development of TG13 On June 9, 2011, the first International Meeting for Fig.5 AnnualnumberoforiginalarticlescitingpapersinTG07 ClinicalAssessmentandRevisionoftheTokyoGuidelines washeld.Inthismeeting,itwasmadeclearthat:(1)TG07 criteria [1, 3–6] and, at the same time, the presentation of should be updated due to the presence of divergence those criteria improved the quality of medical care betweenTG07andrealclinicalsettings;(2)thevalidityof throughout the world, and the usefulness of TG07 has the diagnostic criteria for acute cholangitis was to be become a target of appraisal from clinical viewpoints [10, investigated on the basis of retrospective analysis of 11]. TG07 should have been prepared primarily on the patients with acute cholangitis collected from multiple basisofevidence.However,duetothepaucityofevidence, institutions; (3) there was divergence between severity it was completed through combining ‘‘best available evi- assessment and clinical judgement for acute cholangitis. dence’’ and the worldwide knowledge cultivated at the 2. The Second International Meeting for the develop- international consensus meeting. Therefore, a test by cli- ment of TG13 nicians for its usefulness is indispensable. TG07 has now On September 6, 2011, the Second International Meet- reached the stage when it can be further improved on the ing for Clinical Assessment and Revision of the Tokyo basis of evidence and consensus as well as feedback from Guidelines was held. At the meeting, the overall action clinical practice. plansforthenewguidelinesweredeterminedwiththedraft Ingeneral,followingthepublicationofclinical practice revision of the TG07 and the newly introduced Grades of guidelines, newfindingsare reportedconcerningdiagnosis Recommendation,Assessment,DevelopmentandEvaluation 123 JHepatobiliaryPancreatSci(2013)20:1–7 5 (GRADE) systems to provide the levels of evidence and the quality of the study was re-assessed based on the lim- grade of recommendations. In this meeting, antimicrobial itations and the body of evidence was re-classified as therapy was mainly discussed. Using the two international ‘‘moderate’’ evidence. Observational studies (a non-ran- meetings mentioned above as a basis, the revision work of domizedstudy,acohortstudy,oracase–controlstudy)are TG07 started in 2011. classified as having low-level evidence in general. The 3. The validation study for acute cholangitis was pre- bodyofevidencemaybeupgradedto‘‘highlevel’’ifithas sented in Kiriyama et al.’s paper [13]. significant influences in clinical practice. Case series or 4. The clinical study for Charcot’s triad was also case reports are classified as having very low evidence, in described in Kiriyama et al.’s paper [13]. general. It is extremely rare that the body of evidence is 5. The validation study for acute cholecystitis was pre- re-classifiedtoahigherlevel.However,reportsofcasesof sented in Yokoe et al.’s paper [14]. deaths due to complications or cases of significant side 6. Third International Meeting for the development of effects may be considered as a higher level. TG13 The strength of recommendations was classified as On April 11, 2012, the Third International Meeting for ‘‘high (strong)’’ (recommendation 1) and ‘‘low (weak)’’ the Clinical Assessment and Revision of Tokyo Guide- (recommendation 2). Four factors that determine the lines was held. In this meeting, the final draft of the strength of recommendations are: (1) the quality of evi- updated Tokyo Guidelines was prepared on the basis of dence; (2) sense of value and patient’s preference (less the evidence from the validation studies of TG07. To burden on staff members and patients); (3) net profits and begin with, a discussion took place involving the updated cost/source(costsaving);and(4)benefitsandharmburden new diagnostic criteria for which sensitivity and speci- (benefits and risks). The general decision was made by ficity had been improved, the new severity assessment taking into account these four factors. Strong and weak criteria adapted for practical medical care, new flowcharts recommendations were then determined by the Tokyo prepared for reducing divergence between evidence and GuidelinesRevisionCommittee.Astrongrecommendation clinical care, recommended medical care to which new suggests that desirable effects clearly exceed undesirable evidence had been added, the new idea of gallbladder effects and is applied to recommendations on which more drainage and biliary drainage methods in clinical use, than 70 % of the members of the Tokyo Guidelines antimicrobial therapy, and the role of surgical Revision Committee have agreed. The use of ‘‘We rec- intervention. ommend …’’ has been adopted for the style of the The concept and methodology of management bundles expression. A weak recommendation shows that desirable was introduced and discussed as tools for the effective effects probably exceed undesirable effects and the use of dissemination and implementation of clinical practice ‘‘We suggest …’’ has been adopted. guidelines by utilizing the GRADE systems for evidence The recommendation 1 level A (strong recommenda- assessment, and the concept of the grade of recommenda- tion;evidencelevelhigh),1B,1C,1D,2A,2B,2C,and2D tion. As the results of the Third International Meeting for (weak recommendation; evidence level very low) are theClinicalAssessmentandRevisionofTokyoGuidelines, shown at the end of recommendations. However, cases the final draft was prepared through an international email with strong recommendation (recommendation 1) may conference with overseas co-authors. Thus TG13 was include those cases for which ‘‘to perform …’’ is strongly formulated. recommended and those for which ‘‘not to perform …’’ is strongly recommended. The GRADE systems Introduction of bundles for the management of acute The assessment of the evidence and the grading of rec- cholangitis and cholecystitis ommendations in TG13 are based on the GRADE systems reported in 2004 and 2008 by the working team for the Wepresentedanddiscussedtheconceptandthemethodof GRADE [15–17]. The assessment of the quality of evi- management bundles in TG13. Concrete objectives and dence and the strength of recommendation are shown in anticipated effects of the bundles are as follows: (1) to Figs. 7 and 8), respectively. achieve improved prognosis by using bundles of treatment Intheassessmentofthequalityofevidence,thelevelof methodswithevidencepresentedintheguidelines(TG13); evidence is classified as ‘‘high’’ (level A), ‘‘moderate’’ (2) to achieve higher compliance and remove barriers (level B), ‘‘low’’ (level C), or ‘‘very low’’ (level D). A among institutions by presenting a list of guidelines in the randomized trial is, in general, classified as having high- form of bundles; (3) to carry out a survey involving com- level evidence. However, due to limitations in each study, pliancewiththeitemsofthemedicalcarerecommendedby 123 6 JHepatobiliaryPancreatSci(2013)20:1–7 Fig.7 GRADEsystem(quality Initial quality of Study design Lower if Higher if ofevidence)[15–17] evidence High RCT, systematic Study limitations: Magnitude of effect: review, meta- 1 Serious 2 Very strong analysis 2 Very serious 1 Strong Inconsistency: Moderate 1 Serious Dose-response 2 Very serious gradient Low Observational Indirectness: 1 study 1 Serious (cohort study, case 2 Very serious All plausible control study Impression: confounders would Very low Any other 1 Serious have reduced the evidence 2 Very serious effect (case series, case Publication bias 1 study) 1 likely 2 Very likely Definition: Overall quality of evidence across studies for the outcome level A High level B Moderate level C Low level D Very low 1. How to judge a Grade of recommendation References Totally judgment with evidence, harm and benefit Level of evidence A, B, C, D 1. Takada T, Kawarada Y, Nimura Y, Yoshida M, Mayumi T, SekimotoM,etal.Background:TokyoGuidelinesfortheman- Patient’spreference Yes, No agement of acute cholangitis and cholecystitis. J Hepatobiliary Harm and benefit Yes, No PancreatSurg.2007;14:1–10. Cost effectiveness Yes, No 2. Tokyo Guidelines for the management of acute cholangitis and 2. How to show a Grade of recommendation 2steps cholecystitis. Proceedings of a consensus meeting, April 2006, Recommendation 1: Strong recommendation(Do it, Don’t do it): Tokyo,Japan.JHepato-BiliaryPancreatSurg.2007;14:1–121. 3. MiuraF,TakadaT,KawaradaY,NimuraY,WadaK,HirotaM, Over 70 of clinical practitioners will agree et al. Flowcharts for the diagnosis and treatment of acute cho- = We recommend langitis and cholecystitis: Tokyo guidelines. J Hepatobiliary Recommendation 2 Weak recommendation (probably do it, PancreatSurg.2007;14:27–34. probably don’t do it) 4. Wada K, Takada T, Kawarada Y, Nimura Y, Miura F, Yoshida Less than 70 will agree = We suggest M, et al. Diagnostic criteria and severity assessment of acute cholangitis: Tokyo guidelines. J Hepatobiliary Pancreat Surg. Fig.8 GRADEsystem(gradeofrecommendation)[15–17] 2007;14:52–8. 5. HirotaM,TakadaT,KawaradaY,NimuraY,MiuraF,HirataK, et al. Diagnostic criteria and severity assessment of acute cho- the guidelines and to provide guidelines for conducting a lecystitis: Tokyo guidelines. J Hepatobiliary Pancreat Surg. surveyconcerningchangesinmedicalcarebeforeandafter 2007;14:78–82. 6. Strasberg SM. Acute calculous cholecystitis. N Engl J Med. publication of TG13. 2008;358:2804–11. 7. Cameron JL, Cameron AM. Current surgical therapy. 10th ed. ElsevierMosby:Philadelphia.2011;p.345–348. Summary 8. DooleyJS,LokA,BurroughsA,HeathcoteJ.Sherlock’sdiseases of the liver and biliary system, 12th ed. Blackwell: Hoboken; 2011. This paper presents the background of TG07, its clinical 9. Solomkin JS, Mazuski JE, Bradley JS, Rodvold KA, Goldstein impact since publication, the clinical appraisal emerging EJ, Baron EJ, et al. Diagnosis and management of complicated fromclinicalresearch,theprocessofrevisionofTG07,and intra-abdominal infection in adults and children: guidelines by theSurgicalInfectionSocietyandtheInfectiousDiseasesSociety thedevelopmentofTG13.Theguidelinesneedcontinuous ofAmerica.ClinicalInfectDis.2010;50(2):133–64. evaluation and revision. TG13 has been developed to 10. Murata A, Matsuda S, Kuwabara K, Fujino Y, Kubo T, et al. improvethequalityofmedicalcareforpatientswithacute Evaluation of compliance with the Tokyo Guidelines for the cholangitis and cholecystitis. The guidelines should be management of acute cholangitis based on the Japanese admin- istrative database associated with the Diagnosis Procedure widely utilized and prospective clinical studies are needed Combinationsystem.JHepatobiliaryPancreatSci.2010;18:53–9. for further improvement in the near future. 11. Yokoe M, Takada T, Mayumi T, Yoshida M, Hasegawa H, Norimizo S, et al. Accuracy of the Tokyo Guidelines for the Conflictofinterest None. diagnosis of acute cholangitis and cholecystitis taking into 123 JHepatobiliaryPancreatSci(2013)20:1–7 7 consideration the clinical practice patternin Japan. JHepatobil- 15. Atkins D, Eccles M, Flottorp S, Guyatt GH, Henry D, Hill S, iaryPancreatSci.2011;18:250–7. etal.Systemsforgradingthequalityofevidenceandthestrength 12. Shekelle PG, Ortiz E, Rhodes S, Morton SC, Eccles MP, of recommendations I: critical appraisal of existing approaches. GrimshawJM,WoolfSH.ValidityoftheAgencyforHealthcare The GRADE Working Group. BMC Health Serv Res. 2004; ResearchandQualityclinicalpracticeguidelines:howquicklydo 4(1):38. guidelinesbecomeoutdated?JAMA.2001;286:1461–7. 16. Guyatt GH, Oxman AD, Vist GE, Kunz R, Falck-Ytter Y, 13. Kiriyama S,Takada T,Strasberg SM, SolomkinJS,Mayumi T, Alonso-CoelloP,etal.Ratingqualityofevidenceandstrengthof PittHA,etal.Newdiagnosticcriteriaandseverityassessmentof recommendations. GRADE: an emerging consensus on rating acute cholangitis in revised Tokyo guidelines. J Hepatobiliary quality of evidence and strength of recommendations. BMJ. PancreatSci.2012;19:548–56. 2008;336:924–6. 14. Yokoe M, Takada T, Strasberg SM, Solomkin JS, Mayumi T, 17. Guyatt GH, Oxman AD, Kunz R, Vist GE, Falck-Ytter Y, GomiH,etal.Newdiagnosticcriteriaandseverityassessmentof Schu¨nemannHJ,etal.Ratingqualityofevidenceandstrengthof acute cholesystitis in revised Tokyo guidelines. J Hepatobiliary recommendations. What is ‘‘quality of evidence’’ and why is it PancreatSci.2012;19:578–85. importanttoclinicians?BMJ.2008;336:995–8. 123 JHepatobiliaryPancreatSci(2013)20:8–23 DOI10.1007/s00534-012-0564-0 GUIDELINE TG13: Updated Tokyo Guidelines for acute cholangitis and acute cholecystitis TG13 current terminology, etiology, and epidemiology of acute cholangitis and cholecystitis YasutoshiKimura • TadahiroTakada • StevenM.Strasberg • HenryA.Pitt • DirkJ.Gouma • O.JamesGarden • Markus W. Bu¨chler • John A. Windsor • Toshihiko Mayumi • Masahiro Yoshida • Fumihiko Miura • Ryota Higuchi • Toshifumi Gabata • Jiro Hata • Harumi Gomi • Christos Dervenis • Wan-Yee Lau • Giulio Belli • Myung-Hwan Kim • Serafin C. Hilvano • Yuichi Yamashita Publishedonline:11January2013 (cid:2)JapaneseSocietyofHepato-Biliary-PancreaticSurgeryandSpringer2012 Abstract While referring to the evidence adopted in the cholecystitis is the presence of stones. Next to stones, the Tokyo Guidelines 2007 (TG07) as well as subsequently most significant etiology of acute cholangitis is benign/ obtained evidence, further discussion took place on ter- malignant stenosis of the biliary tract. On the other hand, minology,etiology,andepidemiologicaldata.Inparticular, there is another type of acute cholecystitis, acute acalcu- new findings have accumulated on the occurrence of lous cholecystitis, in which stones are not involved as symptoms in patients with gallstones, frequency of severe causative factors. Risk factors for acute acalculous chole- cholecystitis and cholangitis, onset of cholecystitis cystitis include surgery, trauma, burn, and parenteral and cholangitis after endoscopic retrograde cholangiopan- nutrition.After2000,themortalityrateofacutecholangitis creatography and medications, mortality rate, and recur- has been about 10 %, while that of acute cholecystitis has rence rate. The primary etiology of acute cholangitis/ generally been less than 1 %. After the publication of TG07, diagnostic criteria and severity assessment criteria were standardized, and the distribution of cases according Electronicsupplementarymaterial Theonlineversionofthis to severity and comparison of clinical data among target article(doi:10.1007/s00534-012-0564-0)containssupplementary populations have become more subjective. The concept of material,whichisavailabletoauthorizedusers. Y.Kimura(&) M.W.Bu¨chler DepartmentofSurgicalOncologyandGastroenterological DepartmentofSurgery,UniversityofHeidelberg,Heidelberg, Surgery,SapporoMedicalUniversitySchoolofMedicine, Germany S-1,W-16,Chuo-ku,Sapporo060-8543,Japan e-mail:[email protected] J.A.Windsor DepartmentofSurgery,TheUniversityofAuckland,Auckland, T.Takada(cid:2)F.Miura NewZealand DepartmentofSurgery,TeikyoUniversitySchoolofMedicine, Tokyo,Japan T.Mayumi DepartmentofEmergencyandCriticalCareMedicine, S.M.Strasberg IchinomiyaMunicipalHospital,Ichinomiya,Japan SectionofHepatobiliaryandPancreaticSurgery,Washington UniversityinSaintLouisSchoolofMedicine, M.Yoshida SaintLouis,MO,USA ClinicalResearchCenterKakenHospital,International UniversityofHealthandWelfare,Ichikawa,Japan H.A.Pitt DepartmentofSurgery,IndianaUniversitySchoolofMedicine, R.Higuchi Indianapolis,IN,USA DepartmentofSurgery,InstituteofGastroenterology, TokyoWomen’sMedicalUniversity,Tokyo,Japan D.J.Gouma DepartmentofSurgery,AcademicMedicalCenter,Amsterdam, T.Gabata TheNetherlands DepartmentofRadiology,KanazawaUniversityGraduate SchoolofMedicalScience,Kanazawa,Japan O.J.Garden ClinicalSurgery,TheUniversityofEdinburgh,Edinburgh,UK 123 JHepatobiliaryPancreatSci(2013)20:8–23 9 healthcare-associated infections is important in the current mortality rate, and recurrence rate are introduced along treatment of infection. The treatment of acute cholangitis with epidemiological data. and cholecystitis substantially differs from that of com- munity-acquired infections. Cholangitis and cholecystitis as healthcare-associated infections are clearly described in Terminology the updated Tokyo Guidelines (TG13). Free full-text articles anda mobile application ofTG13 Acute cholangitis are available via http://www.jshbps.jp/en/guideline/tg13. html. Definition Keywords Terminology (cid:2) Etiology (cid:2) Epidemiology (cid:2) Acute cholangitis is a morbid condition with acute Acute cholangitis (cid:2) Acute cholecystitis inflammation and infection in the bile duct [1, 2]. Pathophysiology Introduction The onset of acute cholangitis involves two factors: (1) Acute biliary infection comprises manifold disease con- increased bacteria in the bile duct, and (2) elevated intra- cepts and is mostly separated into [1] acute cholangitis, a ductal pressure in the bile duct allowing translocation of systemic infectious disease that is occasionally life-threat- bacteria or endotoxin into the vascular and lymphatic ening and requires immediate treatment, and [2] acute system(cholangio-venous/lymphaticreflux).Becauseofits cholecystitis, frequently presentinga mild clinical course. anatomicalcharacteristics,thebiliarysystemislikelytobe The definition, pathophysiology, and epidemiology of affected by the elevated intraductal pressure. In acute acutecholangitisarepresentedintheTokyoGuidelinesfor cholangitis, bile ductules tend to become more permeable the management of acute cholangitis and chlecystitis 2007 tothetranslocationofbacteriaandtoxinswiththeelevated (TG07) [1], while the updated Tokyo Guidelines (TG13) intraductal biliary pressure. This process results in serious present more subjective data acquired throughout the and fatal infections such as hepatic abscess and sepsis [1]. revisionofTG07.Asforthedataofcurrentclinicaltrialsin particular, the data concerning frequency of severe cases, Historical aspect of terminology J.Hata Signs of hepatic fever Hepatic fever was a term used for DepartmentofEndoscopyandUltrasound,KawasakiMedical thefirsttimebyCharcotinhisreportpublishedin1887[3]. School,Okayama,Japan Intermittent fever accompanied by chills, right upper H.Gomi quadrant abdominal pain, and jaundice have been estab- CenterforClinicalInfectiousDiseases,JichiMedicalUniversity, lished as Charcot’s triad. Tochigi,Japan Acute obstructive cholangitis Acute obstructive cholan- C.Dervenis FirstDepartmentofSurgery,AgiaOlgaHospital,Athens, gitiswasdefinedbyReynoldsandDargan[4]in1959asa Greece syndrome consisting of lethargy or mental confusion and shock, as well as fever, jaundice, and abdominal pain W.-Y.Lau caused by biliary obstruction. They indicated that emer- FacultyofMedicine,TheChineseUniversityofHongKong, HongKong,HongKong gency surgical biliary decompression was the only effec- tive procedure for treating the disease. These five G.Belli symptoms were thus called Reynold’s pentad. GeneralandHPBSurgery,LoretoNuovoHospital,Naples,Italy M.-H.Kim Longmire’s classification Longmire classified patients DepartmentofInternalMedicine,AsanMedicalCenter, withthreecharacteristicsofintermittentfeveraccompanied UniversityofUlsan,Seoul,Korea by chills and shivering, right upper quadrant abdominal pain, and jaundice as acute suppurative cholangitis, and S.C.Hilvano DepartmentofSurgery,CollegeofMedicine-PhilippineGeneral those with lethargy or mental confusion and shock along Hospital, UniversityofthePhilippines,Manila,Philippines with the triad as acute obstructive suppurative cholangitis (AOSC). He also reported that the latter corresponded to Y.Yamashita themorbidityofacuteobstructivecholangitisasdefinedby DepartmentofGastroenterologicalSurgery,FukuokaUniversity SchoolofMedicine,Fukuoka,Japan Reynolds [5]. 123 10 JHepatobiliaryPancreatSci(2013)20:8–23 However, terms such as acute obstructive cholangitis Pathological classification and acute obstructive suppurative cholangitis (AOSC) are not appropriate as current clinical terminology because (1) Edematous cholecystitis: 1st stage (2–4 days) The their definition is conceptual and ambiguous. gallbladder has interstitial fluid with dilated capillar- ies and lymphatics. The gallbladder wall is edema- Acute cholangitis/cholecystitis as healthcare-associated tous. Gallbladder tissue is intact histologically with infections edema in the subserosal layer [1]. (2) Necrotizing cholecystitis: 2nd stage (3–5 days) The In the US IDSA/SIS guidelines on abdominal infection, gallbladder has edematous changes with areas of acute cholangitis/cholecystitis refers to biliary tract infec- hemorrhage and necrosis. When the gallbladder wall tion that has developed in any of the following patients: issubjecttoelevatedinternalpressure,thebloodflow patientswithahistoryoflessthan12 monthshospitalstay, is obstructed with histological evidence of vascular patients undergoing dialysis, patients staying at nursing thrombosisandocclusion.Thereareareasofscattered home/rehabilitation facility, and patients in an immune- necrosis but they are superficial and do not involve compromised state [6]. the full thickness of the gallbladder wall [1] (Fig. 1). That concept has been extrapolated, and acute cho- langitis/cholecystitisasahealthcare-associatedinfection inJapanreferstoinfectionthathasdevelopedinpatients a (long-term recumbency, admission to nursing home, gastrostomy, tracheostomy, repeated aspiration pneu- monia,bedsore,uretheralcatheterplacement,historyof recent postoperative infection, or undergoing antimi- crobial therapy due to other diseases) at risk of having resistant bacteria (bacteria with a high minimum inhib- itory concentration, MIC). Those infections should be treated independently from community-required infections. Acute cholecystitis Definition b Acute inflammatory disease of the gallbladder, often attributable to gallstones, but many factors, such as ische- mia, motility disorders, direct chemical injury, infections by microorganism, protozoon and parasites, collagen dis- ease, and allergic reaction are also involved [1]. Pathophysiology In the majority of patients, gallstones are the cause of acute cholecystitis. The process is one of physical obstruction of the gallbladder at the neck or in the cystic duct by a gallstone. This obstruction results in increased pressure in the gallbladder. There are two factors which determine the progression to acute cholecystitis—the degree of obstruction and the duration of the obstruction. Fig.1 Necrotizing cholecystitis. a Contrast-enhanced CT images If the obstruction is partial and of short duration, the show discontinuity of the gallbladder wall, suggesting possible patient experiences biliary colic. If the obstruction is presence of necrosis in a portion of the wall. b Resected specimen complete and of long duration, the patient develops acute showing extensive falling-off of the gallbladder membrane, erosion, ulcer,andexposedfascia.Histologically,necrosisofthegallbladder cholecystitis. If the patient does not receive early treat- wall and suppurative inflammation accompanying abscess (data not ment, the disease becomes more serious and complica- shown)wereobservedwithfibrillationandregeneratinghyperplastic tions can occur [1]. epitheliumasbackground 123