w w w . e l s e v i e r . e s / e i m c
Consensus statement
Executive Summary of the Consensus Statement of the Spanish Society of Infectious Diseases and Clinical Microbiology (SEIMC), the Spanish Society of Tropical Medicine and International Health
(SEMTSI), the Spanish Association of Surgeons (AEC), the Spanish Society of Pneumology and Thoracic Surgery (SEPAR), the Spanish Society of Thoracic Surgery (SECT), the Spanish Society of Vascular and Interventional Radiology (SERVEI), and the Spanish Society of Paediatric Infectious Diseases (SEIP), on the Management of Cystic Echinococcosis 夽
Moncef Belhassen-Garcia
a,∗, Óscar Balboa Arregui
b, Eva Calabuig-Mu˜noz
c, David Carmena
d, Maria del Carmen Esteban Velasco
e, Marta Fuentes Gago
f, Victoria Fumado Pérez
g,
Jesús García Alonso
h, Milagros García López Hortelano
i, Luis Miguel González Fernández
e, Juan María Herrero Martínez
j, Manuel José Iglesias Iglesias
e, Marcelo Jiménez López
f, Rogelio López-Vélez
k, Luis Mu˜noz-Bellvis
l, Antonio Muro
m, Javier Pardo-Lledías
n, Maria Pe˜naranda-Vera
o, Maria Jesús Perteguer-Prieto
p, Albert Picado
q,
Jose Edecio Qui˜nones Sampedro
e, Azucena Rodríguez-Guardado
r, ͘nigo Royo Crespo
s,
Fernando Salvador
t, Adrian Sánchez-Montalvá
u, Diego Torrús Tendero
v, Luis Velasco Pelayo
haServiciodeMedicinaInterna,SeccióndeEnfermedadesInfecciosas,ComplejoAsistencialUniversitariodeSalamanca(CAUSA),InstitutodeInvestigaciónBiomédicadeSalamanca (IBSAL),CentrodeInvestigaciónenEnfermedadesTropicalesdelaUniversidaddeSalamanca(CIETUS),UniversidaddeSalamanca,Salamanca,Spain
bServiciodeRadiodiagnóstico,HospitalClínicoUniversitariodeSantiagodeCompostela,Spain
cUnidaddeEnfermedadesInfecciosasdelHospitalUniversitarioyPolitécnicoLaFe,Valencia,Spain
dLaboratoriodeReferenciaeInvestigaciónenParasitología,CentroNacionaldeMicrobiología,Majadahonda,Madrid,Spain
eServiciodeCirugía,CAUSA,IBSAL,UniversidaddeSalamanca,Salamanca,Spain
fServiciodeCirugíaTorácica,CAUSA,IBSAL,UniversidaddeSalamanca,Salamanca,Spain
gSantJoandeDéu,Barcelona,Spain
hServiciodeRadiodiagnóstico,CAUSA,IBSAL,UniversidaddeSalamanca,Spain
iServiciodePediatría,EnfermedadesInfecciosayTropicales,UnidaddeVacunaciónInternacionalyNi˜noViajero,HospitalUniversitarioInfantilLaPaz-HospitalCarlosIII,Madrid, Spain
jServiciodeMedicinaInterna,HospitalUniversitarioLaPaz,Madrid,Spain
kUnidaddeReferenciaNacionalparaEnfermedadesTropicales,ServiciodeEnfermedadesInfecciosas,HospitalUniversitarioRamónyCajal,IRYCIS,Madrid,Spain
lServiciodeCirugía,CAUSA,IBSAL,CentrodeInvestigaciónBiomédicaenReddeCáncer,InstitutoSaludCarlosIII(CIBERONC),UniversidaddeSalamanca,Spain
mGrupodeInvestigaciónEnfermedadesInfecciosasyTropicales(e-INTRO),IBSAL,CIETUS,FacultaddeFarmacia,UniversidaddeSalamanca,Salamanca,Spain
nServiciodeMedicinaInterna,HospitalUniversitarioMarquésdeValdecilla,UniversidaddeCantabria,IDIVAL,Santander,Spain
oHospitalSonEspases,PalmadeMallorca,Spain
pCentroNacionaldeMicrobiología,Madrid,Spain
qFoundationforInnovativeNewDiagnostics-FIND,Geneva,Switzerland
rUnidaddeEnfermedadesTropicales,HospitalUniversitariodeCabue˜nes,Gijón,Spain
Abbreviations: AE,alveolarechinococcosis;CE,cysticechinococcosis;CRP,C-reactiveprotein;CT,computedtomography;DALY,disability-adjustedlifeyear;DNA, deoxyribonucleicacid;ERCP,endoscopicretrogradecholangiopancreatography;FDG,fluorodeoxyglucose;HF,hydatidfluid;LAMP,loop-mediatedisothermalamplification ofnucleicacid;MoC,aTmodifiedcatheterisationtechnique;MR,magneticresonance;PAIR,puncture,aspiration,injectionandreaspiration;PAIRD,puncture,aspiration,injec- tion,reaspirationanddrainage;PET,positronemissiontomography;PEVAC,modifiedpercutaneousevacuation;RFA,radiofrequencyablation;Sen,sensitivity;Spe,specificity;
VATS,video-assistedthoracoscopicsurgery;W&W,watchandwait;WHO,WorldHealthOrganization;WHO-IWGE,WHOInformalWorkingGrouponEchinococcosis.
夽ThecompleteconsensusstatementisavailableasAppendixA.Supplementarydata.
∗Correspondingauthor.
E-mailaddress:[email protected](M.Belhassen-Garcia).
https://doi.org/10.1016/j.eimc.2019.10.015
0213-005X/©2019PublishedbyElsevierEspa˜na,S.L.U.
2529-993X
sServiciodeCirugíaTorácica,HospitalUniversitarioMiguelServet,HospitalClínicoUniversitarioLozanoBlesa,IIS,Aragón,Zaragoza,Spain
tServicioEnfermedadesInfecciosas,HospitalUniversitarioValld’Hebron,PROSICS,Barcelona,Spain
uServiciodeEnfermedadesInfecciosas,HospitalUniversitarioValld’Hebron,PROSICSBarcelona,UniversidadAutónomadeBarcelona,Barcelona,Spain
vUnidaddeEnfermedadesInfecciosas,HospitalGeneralUniversitariodeAlicante,InstitutodeInvestigaciónSanitariayBiomédicadeAlicante,ISABIAL–FISABIO,Alicante,Áreade Parasitología,UniversidadMiguelHernández,Spain
a r t i c l e i n f o
Keywords:
Hydatidosis Cysticechinococcosis Echinococcusgranulosus Guidelines
a b s t r a c t
TheSpanishSocietyofInfectiousDiseasesandClinicalMicrobiology(SEIMC),theSpanishSocietyof TropicalMedicineandInternationalHealth(SEMTSI),theSpanishAssociationofSurgeons(AEC),the SpanishSocietyofPneumologyandThoracicSurgery(SEPAR),theSpanishSocietyofThoracicSurgery (SECT),theSpanishSocietyofVascularandInterventionalRadiology(SERVEI),andtheSpanishSociety ofPaediatricInfectiousDiseases(SEIP)considereditpertinenttoissueaconsensusstatementonthe managementofcysticechinococcosis(CE)toguidehealthcareprofessionalsinthecareofpatientswith CE.
Specialistsfromseveralfields(clinicians,surgeons,radiologists,microbiologists,andparasitologists) identifiedthemostclinicallyrelevantquestionsanddevelopedthisConsensusStatement,evaluating theavailableevidence-baseddatatoproposeaseriesofrecommendationsonthemanagementofthis disease.ThisConsensusStatementisaccompaniedbythecorrespondingreferencesonwhichthese recommendationsarebased.
Priortopublication,themanuscriptwasopenforcommentsandsuggestionsfromthemembersofthe SEIMCandthescientificcommitteesandboardsofthevarioussocietiesinvolved.
©2019PublishedbyElsevierEspa˜na,S.L.U.
Resumen ejecutivo de la Declaración de consenso de la Sociedad Espa ˜ nola de Enfermedades Infecciosas y Microbiología Clínica (SEIMC), la Sociedad Espa ˜ nola de Medicina Tropical y Salud Internacional (SEMTSI), la Asociación Espa ˜ nola de Cirujanos (AEC), la Sociedad Espa ˜ nola de Neumología y Cirugía Torácica (SEPAR), la Sociedad Espa ˜ nola de Cirugía Torácica (SECT), la Sociedad Espa ˜ nola de Radiología Vascular e Intervencionista (SERVEI) y la Sociedad Espa ˜ nola de Infectología Pediátrica (SEIP) sobre el tratamiento de la equinococosis quística
Palabrasclave:
Hidatidosis
Equinococosisquística Echinococcusgranulosus Declaracióndeconsenso
r e s u m e n
LaSociedadEspa˜noladeEnfermedadesInfecciosasyMicrobiologíaClínica(SEIMC),laSociedadEspa˜nola deMedicinaTropicalySalud Internacional(SEMTSI),laAsociación Espa˜noladeCirujanos(AEC),la SociedadEspa˜noladeNeumologíayCirugíaTorácica(SEPAR),laSociedadEspa˜noladeCirugíaTorácica (SECT),laSociedadEspa˜noladeRadiologíaVasculareIntervencionista(SERVEI)ylaSociedadEspa˜nola deInfectologíaPediátrica(SEIP)hanconsideradopertinentelaelaboracióndeunadeclaracióndecon- sensosobreeltratamientodelaequinococosisquística(EQ)quesirvadeayudaalpersonalsanitarioen laatencióndepacientesconEQ.
Variostiposdeprofesionales(médicos,cirujanos,radiólogos,microbiólogosyparasitólogos)hanselec- cionadolaspreguntasmásclínicamenterelevantesyhandesarrolladoestaDeclaracióndeconsenso,en laqueevalúanlosdatosbasadosenlaevidenciadisponiblesparaproponerunaseriederecomendaciones sobreeltratamientodeestaenfermedad.EstaDeclaracióndeconsensoseacompa˜nadelabibliografía correspondientequefundamentaestasrecomendaciones.
Antesdesupublicación,elmanuscritoestuvoabiertoacomentariosysugerenciasdelosmiembrosde laSEIMCydeloscomitéscientíficosyjuntasdirectivasdelasdiferentessociedadesimplicadas.
©2019PublicadoporElsevierEspa˜na,S.L.U.
Introductionandrationale
Cystic echinococcosis (CE) or hydatid disease is a zoonosis causedbythetapewormEchinococcusgranulosussensulato;dogs arethedefinitivehosts,andhumansareanaccidentalintermediate host.Duetoitsimpactinterms ofmorbidity,itshigher preva- lenceindevelopingareas,andthelackofinvestmentinresearch, echinococcosis is includedon the World Health Organization’s (WHO)listofNeglectedTropicalDiseases.AlthoughCEhasaworld- widedistribution,mosthumancasesareconcentrated inSouth America, North and East Africa, theMiddle East, and countries inCentral andWesternAsia.In Europe,it isparticularlypreva- lentinMediterraneancountriessuchasGreece,ItalyandPortugal.
Spainisconsideredahighlyendemicarea;therateoftransmis- sionremainshighbutthereisavariablegeographicaldistribution.
ThediagnosisofCEshouldbemadeaccordingtotheWHO cri- teria. ThemanagementofCEiscomplex,and currently,despite WHOrecommendations,thereisnoconsensusonitsmanagement.
Essentially,therearethreecategoriesoftreatment,whichareoften usedincombination:(i)surgery,(ii)percutaneoustechniques,and (iii)antiparasiticdrugs.
The management varies considerably depending on (i) the patientcharacteristics,(ii)thefeatures ofthecyst,and (iii) the resourcesavailableatthehealthcarefacility.Currently,thetreat- mentofchoiceissurgery,althoughseveralalternativetechniques areavailable.ThePAIRtechnique(puncture,aspiration,injection
andreaspiration)hasbeenintroducedandcanbeusedinsteadof surgeryinselectedcases.Theusefulnessofothermethodssuch asmodifiedcatheterisation(MoCaT),modifiedpercutaneousevac- uation(PEVAC),immunetherapies,chemo-radioisotopetherapy, andradiofrequencyablation(RFA)mustbecomparedinthefuture.
Antiparasiticdrugs,mainlybenzimidazolesasmonotherapyorin combinationwithotherdrugssuchaspraziquantel,generallyhave secondaryrole:theyaremainlyusedinpatientswhoarenotcandi- datesforsurgery,toreducetheriskofanaphylaxis,dissemination, and/orpostoperativerecurrence,althoughtheyhavealsoshown promisingresultsasaninitialcurativetherapyinspecificsitua- tions.Inrecentyears,thewatchandwait(W&W)approachhasbeen analysedinselectedpatients.
CEthereforeremainsanongoingproblemthatgeneratesintense debateregardingitsoptimaltreatment.
Aimsoftheconsensusstatement
The aimof this Consensus Statement is toprovide thebest possible evidenceon themanagement of CE. Numerousdiffer- entspecialistsinvolvedin themanagementof patientswithCE evaluatedtheavailableevidence-baseddataandmaderecommen- dationsonthevariousaspectsofthedisease.
Methods
Overallmethodologyofthestatement
Asystematicreviewoftheliteraturewascarriedouttoeval- uate data on theepidemiology, clinical features, diagnosis and treatmentoptions of CE. Twenty-three PICO (patient, interven- tion, comparison and outcome) questions were identified, as wellas17additionalquestions.Thesequestionsweredistributed among the different members of the group for evaluation. A PubMed search was performed for the dates 1968 to Decem- ber 2018 for articlesin English or Spanish with the following search terms: “Hydatidosis”, “Hydatid cyst”, “Hydatid disease”,
“CysticEchinococcosis”and“Echinococcusgranulosus”associated witheachoftheitemsexplored(e.g.“surgery”,“treatment”,“cure”,
“relapse”,“recurrence”,“albendazole”,“praziquantel”).Thissearch wascomplementedwitha reviewofMedlineandtheCochrane DatabaseofSystematicReviewsusingthekeyterms“Hydatido- sis”,“Hydatidcyst”,“Hydatiddisease”,“CysticEchinococcosis”and
“Echinococcusgranulosus”. The search wasperformed according to thePRISMA criteria. It was first reviewed by the collabora- torsandthenbythetextcoordinator.Atotalof438publications wereselected,withduplicateorirrelevantpublicationsbeingelim- inated.Queriesregardingtheselectionofspecificreferencesfor eachquestionmaybedirectedtotheauthorsresponsible.Therec- ommendationsarebasedontheSEIMCinternationalcriteriafor consensusguidelinesand theAGREEstandards.Thecoordinator and theauthors ofthe articleissued an editionof theconsen- susstatement,whichwasmadeavailableontheSEIMC website from9-30May2019forexternalreview.Thedocumentwasalso reviewedbythescientificcommitteesofthevariousscientificsoci- etiesinvolved.Alltheauthorshaveapprovedthecontentofthe documentandthefinalrecommendations.
Definitions
CurereferstotheeradicationofanE.granulosusinfectionand mayoccurspontaneouslyorwithtreatment.Giventherecurrent natureoftheinfection,thetermcureisonlyusedincasesinwhich thereisnorecurrenceofinfectionafteralongfollow-upperiod.
Thisfollow-upperiodshouldbeatleast5–10years.
ComplicatedCEisCEthatpresentswithsymptomscausedbythe CE,oftensecondarytoamechanical,infectiousorallergicprocess oracombinationthereof.
Multi-organCEaffectsmorethanoneorgansimultaneously.
MultipleCEisthepresenceoftwoormorelesionsinthesame organ.
SecondaryCEreferstonewcyststhatoccuraftertheruptureofa cyst(primarycyst),spontaneouslyorfollowingsurgeryortrauma.
AtypicallocationreferstoCEoutsidetheliverorlungs.
Persistencereferstothenon-eradicationofE.granulosusinfec- tioninrelationtoanon-eradicationtherapyorawatchandwait (W&W)approach.
Localrecurrenceistherecurrenceofaprimarycystatthesame siteaftertreatmentwithacurativeintention.Thiscanoccurmonths toyearslaterduetoprimarydisseminationoftheprotoscolecesor secondarytocystrupture,whichmaybespontaneous,traumatic, oraccidentalduringsurgery.
Distalrecurrenceistheoccurrenceofcystsinnewsitesafter treatmentwithacurativeintention.Thiscanoccurmonthstoyears laterduetoprimarydisseminationofprotoscolecesorsecondaryto cystrupture,whichmaybespontaneous,traumatic,oraccidental duringsurgery.
Reinfectionreferstoanewcystthatisunrelatedtotheoriginal infection.
Watchandwait,asimplied,thestrategyofwaitingandobserving thepatient.
1.Whatserologicalmethodsareavailableandhowaccuratearethey inthediagnosisofCE?
Recommendations
•Currently,conventionalandrapiddiagnostictestshavealow sensitivityinthecaseofinactivecysts(A-I).
•Classicaltechniquesareprogressivelybeingreplacedwith theuseofpurified,recombinantantigensand/orpeptides.At present,mainlypurifiedorsyntheticantigensderivedmostly fromE.granulosusAg5andAgBareused(A-I).
•Mostrecombinantantigenandpurifiedantigentechniques arehighlyspecific.However,theycanshowcross-reactivity withalveolarechinococcosisandcysticercosis.Theyareusu- allymoresensitiveinmultipleCE(A-I).
2.AremolecularmethodsusefulinthediagnosisofCE?Dothenew parasitologicaltoolshelpinthediagnosis?
Recommendations
•Moleculartechniquesmaybehelpfulinthefuture forthe diagnosisofCE,buttheyarestillintheprocessofoptimisation (A-I).
•GenotypingcanhelpinthemanagementofpatientswithCE andisessentialinthestandardisationandvalidationofthe newserologicaltoolsthatuserecombinantantigens(A-I).
•Inthefuture,minimallyinvasivetechniquessuchasexhaled breathtestsmaybeusedtoassistinthediagnosis(C-III).
3.Whatisthebestfollow-upscheduleforCE?
Recommendations
•Theoptimalfollow-upscheduleforCEhasnotyetbeenestab- lished(C-III).
•Theoretically,follow-upshouldbelong:atleast3–5years, withnoestablishedmaximumduration;insomepatients, follow-upshouldbeindefinite(B-III).
4.SurgicalindicationsinhepaticCE:whenandhow?
Recommendations
•Surgicalisgenerallythetreatmentofchoiceandshouldbe assessedonanindividualbasis(A-II).
•Opensurgeryisthemostacceptedprocedureforthetreat- mentofhepaticCE,especiallyincomplicatedcases(B-II).
•Surgeryisthemainstayoftreatmentforlarge,active,symp- tomaticorcomplicatedcysts:(i)CE2-CE3bcysts,(ii)cysts
>5cm,(iii)cystswithmultipledaughtercysts,(iv)infected cysts,(v)cyststhatcommunicatewiththebiliarytree,and (vi)cyststhatexertamasseffectonadjacentorgans(B-II).
•The relative contraindications for surgery are (i) patients whoareunsuitableforsurgeryduetotheirgeneralstatusor associatedcomorbidities,(ii)multiplecysts,(iii)verysmall, difficult-to-accesscyststhatarepartiallyorcompletelycal- cified(B-II).
5.Whatarethebestandmostfrequentlyusedtechniquesinhepatic CE?Areclassicalsurgicaltechniquesstillthetechniquesofchoice?
WhatisthepreferredstrategyinhepaticCE:radicalsurgeryor conservativetreatment?
Recommendations
•Thesurgicaltechniquesusedshouldbethosethatareappro- priateforthepatient,theirdisease,andthesettinginwhich theoperationwillbeperformed.Asfaraspossible,surgery shouldaimtominimisecomplicationsandrecurrences(B-II).
•Whereverpossible,radicaltechniquesarepreferabletocon- servativetechniques(B-II).
•Anatomical liver resection, total cystopericystectomy and openorpartialcystectomywithorwithoutomentoplastyare themostfrequentlyusedsurgicaltechniques(B-II).
•Theidealapproachshouldbesimple,withcompleteresection ofthecystwithoutrupture.Alleffortsshouldbemadeto protecttheperitonealcavity andavoidintraoperativecyst leakage(B-II).
•Conservativeproceduresaresafeandlesscomplexthanradi- calprocedures,althoughtheassociatedriskofmorbidityand recurrencemaybehigher(B-II).
6.InhepaticCE,howeffectivearesurgicaltechniquesandwhatare theircomplications?Doeslaparoscopicsurgeryhaveanybene- fitovertraditionalsurgicaltechniques?Arethereanydifferences betweenurgentsurgeryandelectivesurgeryintermsofcompli- cationsorrecurrencerate?
Recommendations
•Appropriate patient selection is essential for successful laparoscopic surgery. Alaparoscopic approach is safeand technicallyfeasible(C-III).
•Laparoscopicsurgeryhassomeadvantagessuchas(i)shorter hospitalstay,(ii)lesspostoperativepain,and(iii)lowerrate ofsurgicalsiteinfection,andcanbeusedinselectedcasesof hepaticCE(C-III).
•Patientswithdeepcysts,cystsinposteriorlobes,nearthe venacava,multiple(>3)cystsorcalcifiedcystsmaynotbe candidatesforlaparoscopicsurgery(C-III).
7.What arethemostfrequently usedsurgicaltechniquesinpul- monaryCE?
Recommendations
•Cystopericystectomyisthesurgicaltechniqueofchoicein pulmonaryCE(C-II).
•In cases with associated lung damage or non-viable parenchyma (complicated cysts and abscesses), the mini- mumpulmonaryresectionnecessaryshouldbeperformed (C-II).
•Capitonnage associated withcystopericystectomy hasnot beendemonstratedtoreducepostoperativeleakage(C-II).
•Surgical approaches via thoracotomy and VATS have comparable outcomes, although VATS has a lower mor- bidity, and is therefore the recommended technique (B-II).
•Patientswithcysticdiseaseinboththerightlowerlobeandin upperhepaticlobesmaybetreatedviaindependentthoracic andabdominalapproachesorviathoracophrenolaparotomy (D-III).
•Percutaneous techniques are not recommended in pul- monaryCEduetothehighriskofcystruptureandsecondary dissemination(B-II).
8. InpulmonaryCE,howeffectivearesurgicaltechniquesandwhat arethepossiblecomplications?
Recommendations
•Surgeryisoneofthebesttreatmentoptionsforpulmonary CE.Ithasalowrateofassociatedmorbidityandmortality (C-II).
•Patientswhoundergosurgeryforcomplicatedcystshavea higherincidenceofpostoperativecomplications(C-II).
9. Whatisthebestapproachfordifficult-to-accesshepaticandpul- monarysites?
Recommendations
•Fromasurgicalperspective,allhepaticsegmentsaretheo- reticallyaccessible(C-III).
•Hepatobiliaryfistulaswiththoracicspreadcanbemanaged surgicallyviaalowthoracotomywithresectionoftheareaof bile-damagedlungandreconstructionwithbiologicalmate- rials (C-III).Theycan alsobe managedconservatively, by drainingthebile,whichencouragesspontaneousclosureof thefistula(C-III).
•VATSorthoracotomyallowsaccesstothewholelung(C-III).
•MostcasesofcardiacCEaretreatedsurgicallyviaamidline sternotomyandusingextracorporealcirculation(C-III).
10. Whatisthemanagementofpatientswithmulti-organCE?
Recommendations
•For any patient with CE, the possibility of multi-organ involvement,especiallyhepatopulmonary,mustbebornein mind.PatientswithhepaticCEshouldhaveasimplechest X-rayorachestCT,andpatientswithpulmonaryCEshould haveanabdominalultrasoundorCT(B-II).
•Astandardisedmedicaltreatmentregimenhasnotyetfully established.Whenmedicaltreatmentistheonlyoption,it shouldbeprolonged,orevenindefinite(avoidingstopping treatment)(B-III).
•Ifthediseaseisveryextensiveandthereisreasonabledoubt about the possibility of complete resection, PAIR and/or chemotherapymaybeconsidered(C-III).
•Inpatientswithmultiplebilateralcysts,asequentialbilateral approachoramidlinesternotomymaybeused(D-III).
•If theupper hepatic segmentsand rightpulmonary lobes areaffected,thesurgicalteammayconsiderthoracophreno- laparotomy, or a sequential independent approach via thoracotomyorVATSandlaparotomyorlaparoscopy(C-II).
11. HowshouldpatientswithatypicallocationCEbemanaged?
Recommendations
•Inpatientsfromendemicareaswithcysticlesions,CEmust beconsideredinthedifferentialdiagnosis(A-I).
•AllpatientswithsuspicionofextrahepaticCEshouldhavea CTofthechestandabdomen(A-III).
•Wherever surgical techniques allow it, the treatment of choiceforatypicallocationCEissurgery(B-I).
•InsplenicCE,althoughsplenectomyiscurative,conservative surgery is preferable;splenectomy shouldbereservedfor patientswithlargecystsinthecentreorclosetothesplenic hilum(A-II).
•Anthelminthictreatmentmustbegivenforatleast2weeks beforeandforupto3monthsaftersurgery(B-III).
•InrenalCE,laparoscopicsurgerycanbeasafeandeffective option(B-III).
•Ifnephrectomyisperformed,thelargestpossibleamountof parenchymashouldbepreserved;totalnephrectomyshould bereservedforcystsonnon-functioningkidneys,largecysts
(occupying theentireparenchyma)or thosewithsignsof infection(B-II).
•Echocardiographyisthetechniqueofchoiceforthediagno- sisofcardiacCE,duetoitswideavailability,highsensitivity, highresolutionanditsabilitytosimultaneouslyanalysethe haemodynamiceffects(B-II).
•In cardiacCE, antiparasitictreatmentprior tosurgerycan increasetheriskofdamagetothecystwallandofcystrupture (B-I).
•ThetreatmentofchoiceincerebralCEisexcisionofthecyst intact,usingtheDowlingtechnique(B-I).
•InCEofthebone,surgeryshouldremovetheaffectedbone andatleast1–2cmofsurroundinghealthybone;intraopera- tiveirrigationshouldbeperformedwithascolicidalsolution ofhypertonicsaline(B-I).
12.What type ofimage-guided interventional techniques arecur- rentlyused?
Recommendations
•PAIRisasafeandeffectivetechniqueinselectedpatients(CE1 andCE3a)(B-II).
•ForCE1andCE3acystslargerthan10cm,aPAIRDdrainage catheterisrequired(B-III).
•Percutaneous techniquesareeffectivefor unilocularcysts, buttheydonothavethesameefficacyinmultilocularcystsor thosewithsolidcomponents.Forsuchcysts,techniquessuch asPEVAC,MoCaTandDMFThavebeendeveloped(C-III).
•Thereis insufficient evidenceonthe modified techniques forthetreatmentofCE2andCE3bcysts,whichalsohavea highermorbidityandmortality;therefore,theyareindicated inpatientswhoarenotsuitablefororrefusesurgery(C-III).
13.Whatistheusualprocedureforimage-guidedinterventionaltech- niques?
Recommendations
•Percutaneous techniquesmust be performedin an inter- ventionsuitewithlifesupport,anaestheticsedation,anda surgicalteamonstand-by(C-III).
•Toavoidcomplications,communicationbetweenthecysts andthebiliary,renal,orbronchialtreemustbeexcluded(C- III).
14.Whatisthebestscolicidalsolution?
Recommendations
•Currentlythereisnoperfectscolicidalagent.Ethanol(95%) andhypertonicsalinesolution(minimum20%concentration) arethescolicidalagentsofchoice,sincetheyarewidelyavail- able,havegoodscolicidalactivity,andarecheap.Theiruse islimited bytheirsideeffectssuchaschemicalsclerosing cholangitisandanaphylacticreactions(B-III).
•Beforeusingethanolorhypertonicsalinesolutionasscolici- dalagents,thepresenceofcysto-biliaryfistulasmustberuled out(B-III).
15.Whataretheindicationsforeachoftheimage-guidedinterven- tionaltechniques?Howeffectiveispercutaneousinterventional treatment?
Recommendations
•PAIRisindicatedforcystsbetween5and10cmthatarestage CL,CE1orCE3a,andforaccessiblemultiplecysts,infected cysts,postsurgicalrecurrenceorafterfailedmedicaltreat- ment(B-III).
•Themodifiedtechniquewithinsertionofadrainagecatheter (PAIRD)canbeperformedinCL,CE1andCE3acystsgreater than10cm(B-III).
•In typeCE2and CE3bcysts, surgeryisindicated,although modified techniques(MoCaTor PEVAC)can beperformed if the patient is not suitable for or refuses surgery (C-III).
•Percutaneoustechniquescanbeusedinpregnantwomenand inchildrenolderthan3years(B-III).
16. What factors influence the choice of antiparasitic treatment?
Which,when,howandforhowlong?Assessmentofsafetyand efficacy.
Recommendations
•Pharmacologicaltreatmentisrecommendedforinoperable ormulti-organCEandasanadjuncttopercutaneoustreat- mentorsurgery(B-II).
•Pharmacological treatmentisnotrecommendedforCE4–5 (B-III).
•Thereareinsufficientdatatoestablishtheoptimumdose, frequency,anddurationoftreatment(B-II).
•BenzimidazolesareusefuldrugsinCE,albendazolebeingthe drugofchoice(A-I).
•BetterresultsareachievedwhensurgeryorPAIRarecom- bined with anthelminthics given before and/or after the procedure(A-I).
•Recommendationsondurationoftreatmentpriortointer- vention range from 1 dayto 3 months,and for after the intervention,from1to3months(B-II).
•Theadditionalbenefitobtainedfrommorethan6months of anthelminthic treatmentis marginal for mostpatients, althoughitisoftengiveninpatientswithmultipleorinoper- ableCE(B-II).
17. Iscombinedanthelminthictreatmentwithalbendazoleandpraz- iquantelbetterthantreatmentwithalbendazolealone?
Recommendations
•Combinedtreatmentwithalbendazoleandpraziquantelmay beconsideredinthethreemedicalsituationsinwhichphar- macological treatment is used: (i) prior to interventional treatment,(ii)afterinterventionaltreatment,and(iii)asan alternativetosurgery(C-II).
•Combined treatment with albendazole and praziquantel beforeaninterventionalprocedurereducestheviabilityof thecysts.Thesterilisingeffectofthecombinationmaybe superiortothatofmonotherapy(C-II).
•Alongerdurationofcombinedtreatmentappearstobeasso- ciatedwithagreaterreductionintheviabilityofthecysts (C-II).
•Treatmentdoseanddurationarenotwelldefined,butitis recommendedtogiveatleast4weeksofcombinedtreatment priortointervention(C-II).
•Combined anthelminthic treatment after an intervention mayreducetheriskofdisseminationandrecurrence,espe- ciallyifleakagehasoccurred(C-II).
•Theuseofcombinedmedicaltreatmentmayhavesomeben- efitin patientswith(i)disseminateddisease,(ii)previous treatmentfailure,(iii)poordiseasecontrolonmonotherapy, or(iv)whensurgeryiscontraindicated.Thedoseandduration ofcombinationtherapyarenotwellestablished(C-II).
18. Arethereanyothersafeandeffectiveanthelminthictreatments?
Recommendation
•Inadditiontoalbendazoleandpraziquantel,otherdrugshave beenusedinthetreatmentofCE,allwithanacceptablesafety profile(B-III).
•Drugs such as nitazoxanide and thiabendazole may have someefficacyinCE(B-III).
19. Inwhichpatientsisawatchandwaitstrategyrecommended?
Recommendations
•The W&W strategy is suggested for the management of patientswithasymptomaticuncomplicatedhepaticcystsin stagesCE4andCE5(B-III).
•Thefollow-upofthesepatientsisimportantandshouldbe long-term,foratleast3–5years(C-III).
20.Whatfollow-upisneededafteratherapeuticprocedure:which patients,how,andforhowlong?Whatarethemostusefultools?
Recommendations
•Initialfollow-upshouldassessearlycomplicationsofsurgery orpercutaneousintervention;latecomplicationsandrecur- renceshouldbeassessedatalaterdate(B-II).
•Thedurationoffollow-upshouldbeindividualisedaccording tothepatient,disease,andtheavailableresources.Itshould lastatleast3years,althoughincertainpatientsismaybe extendedindefinitely(B-II).
•InhepaticCE,follow-upshouldroutinelyinvolveultrasound (B-II).Inotherlocations,CTand/orMRmaybeuseddepend- ingonavailability(B-II).
21.Isserologyusefulinpost-treatmentfollow-up?
Recommendation
•Serology results must be interpreted with cautionin the follow-upofpatientswithCE.Occasionally,areductionin thetitrescanbeassociatedwithcure,andanincreasecanbe associatedwitharecurrence(B-III).
•Inpatientswhohaveundergoneintervention,completeanti- gendetectiontechniquesarenotusefulforfollow-up(C-II).
•InpatientswithstageCE1–CE3acystswhohaveundergone intervention with curativeintent, detection of antibodies againstAgB2tandAg2B2tcanbeusefulforfollow-up,asit candifferentiateactiveinfectionfromcure(B-II).
22.Areradiologicalmethodsusefulinpost-treatmentfollow-up?
Recommendations
•Ultrasoundisthetechniqueofchoiceforthefollow-upofdis- easeintheliver,abdomen,soft-tissues,andlungswithcysts incontactwiththepleura,andanylocationthatisaccessible withultrasound(B-II).
•Iftherearelimitationstoultrasound,CTandMRcanbeused forfollow-up,particularlyMRasitlimitsradiationdoses(C- III).
•Whenitisdifficulttodeterminetheactivityofthecyst,imag- ingtechniquesshould becomplemented withblood tests (C-III).
23. WhatmeasurescanbetakentopreventCE?
Recommendations
•Any measure against CE should be aimed at interrupt- ing the life cycle of the parasite. Interventions can be aimedatthedefinitivehost and/ortheintermediate host (A-I).
•Interventionsaimedatthedefinitivehostareessential,asthe mainriskfactorsinacquiringCEarelinkedtodogs,which representthemostcommonprimarysourceofinfectionin humans(A-III).
Funding
SpanishSocietyofTropicalMedicineandInternationalHealth (SEMTSI).
Conflictsofinterest
Theauthorsdeclarenoconflictofinterest.
Acknowledgements
JuanHerrero-Martinez,JoaquinSalasCoronas,VirginaVelasco Tirado,AmparoLopezBernusandJaraLlenasGarcia,fortheircon- tributiontothecreationoftheseguidelines.
AppendixA. Supplementarydata
Supplementarydataassociatedwiththisarticlecanbefound,in theonlineversion,atdoi:10.1016/j.eimc.2019.10.015.
