Serum amylase and lipase and urinary trypsinogen and amylase for diagnosis of acute pancreatitis

142 Pages·2017·1.52 MB·English

CochraneDatabaseofSystematicReviews
Serum amylase and lipase and urinary trypsinogen and
amylase for diagnosis of acute pancreatitis (Review)
RompianesiG,HannA,KomolafeO,PereiraSP,DavidsonBR,GurusamyKS
RompianesiG,HannA,KomolafeO,PereiraSP,DavidsonBR,GurusamyKS.
Serumamylaseandlipaseandurinarytrypsinogenandamylasefordiagnosisofacutepancreatitis.
CochraneDatabaseofSystematicReviews2017,Issue4.Art.No.:CD012010.
DOI:10.1002/14651858.CD012010.pub2.
www.cochranelibrary.com
Serumamylaseandlipaseandurinarytrypsinogenandamylasefordiagnosisofacutepancreatitis(Review)
Copyright©2017TheCochraneCollaboration.PublishedbyJohnWiley&Sons,Ltd.
TABLE OF CONTENTS
HEADER . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1
ABSTRACT . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1
PLAINLANGUAGESUMMARY . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2
BACKGROUND . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3
Figure1. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 6
OBJECTIVES . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 7
METHODS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 8
RESULTS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 11
Figure2. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 12
Figure3. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 14
Figure4. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 15
Figure5. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 16
Figure6. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 17
DISCUSSION . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 25
AUTHORS’CONCLUSIONS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 27
ACKNOWLEDGEMENTS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 27
REFERENCES . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 27
CHARACTERISTICSOFSTUDIES . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 49
DATA . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 97
Test1.Serumamylase>3timesnormal. . . . . . . . . . . . . . . . . . . . . . . . . . . . 98
Test2.Serumamylase>3timesnormal(sensitivityanalysisexcludingstudieswithincorporationbias). . . . . . 99
Test3.Serumamylase>3timesnormal(sensitivityanalysisexcludingChang2011). . . . . . . . . . . . 99
Test4.Serumamylase>twicenormal. . . . . . . . . . . . . . . . . . . . . . . . . . . . 100
Test5.Serumamylase>twicenormal(sensitivityanalysisexcludingChang2011). . . . . . . . . . . . . 100
Test6.Serumamylase>twicenormal(2to3days). . . . . . . . . . . . . . . . . . . . . . . . 100
Test7.Serumamylase>twicenormal(4to5days). . . . . . . . . . . . . . . . . . . . . . . . 101
Test8.Serumamylase>normal. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 101
Test9.Serumamylase>normal(sensitivityanalysisexcludingstudieswithincorporationbias). . . . . . . . . 102
Test10.Serumamylase>normal(2to3days). . . . . . . . . . . . . . . . . . . . . . . . . 102
Test11.Serumamylase>normal(4to5days). . . . . . . . . . . . . . . . . . . . . . . . . 102
Test12.Serumlipase>3timesnormal. . . . . . . . . . . . . . . . . . . . . . . . . . . . 103
Test13.Serumlipase>3timesnormal(sensitivityanalysisexcludingstudieswithincorporationbias). . . . . . 103
Test14.Serumlipase>3timesnormal(sensitivityanalysisexcludingChang2011). . . . . . . . . . . . . 104
Test15.Serumlipase>twicenormal. . . . . . . . . . . . . . . . . . . . . . . . . . . . . 104
Test16.Serumlipase>twicenormal(sensitivityanalysisexcludingChang2011). . . . . . . . . . . . . 105
Test17.Serumlipase>twicenormal(2to3days). . . . . . . . . . . . . . . . . . . . . . . . 105
Test18.Serumlipase>twicenormal(4to5days). . . . . . . . . . . . . . . . . . . . . . . . 105
Test19.Serumlipase>normal. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 106
Test20.Serumlipase>normal(2to3days). . . . . . . . . . . . . . . . . . . . . . . . . . 106
Test21.Serumlipase>normal(4to5days). . . . . . . . . . . . . . . . . . . . . . . . . . 107
Test22.Urinarytrypsinogen-2>50ng/mL(ActimPancreatitis). . . . . . . . . . . . . . . . . . . 107
Test23.Urinarytrypsinogen-2>50ng/mL(ActimPancreatitis-sensitivityanalysis). . . . . . . . . . . . 108
Test24.Urinarytrypsinogen-2>50ng/mL(quantitativemethod). . . . . . . . . . . . . . . . . . 108
Test25.Urinarytrypsinogen-2onlypositiveormostpositive(thresholdforthisnotavailable). . . . . . . . . 109
Test26.Urinaryamylase>normal(quantitative). . . . . . . . . . . . . . . . . . . . . . . . . 109
Test27.Urinaryamylase1+(qualitative). . . . . . . . . . . . . . . . . . . . . . . . . . . 109
Test28.Urinaryamylase2+(qualitative). . . . . . . . . . . . . . . . . . . . . . . . . . . 110
ADDITIONALTABLES . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 110
APPENDICES . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 121
CONTRIBUTIONSOFAUTHORS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 138
DECLARATIONSOFINTEREST . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 138
Serumamylaseandlipaseandurinarytrypsinogenandamylasefordiagnosisofacutepancreatitis(Review) i
Copyright©2017TheCochraneCollaboration.PublishedbyJohnWiley&Sons,Ltd.
SOURCESOFSUPPORT . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 138
DIFFERENCESBETWEENPROTOCOLANDREVIEW . . . . . . . . . . . . . . . . . . . . . 139
Serumamylaseandlipaseandurinarytrypsinogenandamylasefordiagnosisofacutepancreatitis(Review) ii
Copyright©2017TheCochraneCollaboration.PublishedbyJohnWiley&Sons,Ltd.
[DiagnosticTestAccuracyReview]
Serum amylase and lipase and urinary trypsinogen and
amylase for diagnosis of acute pancreatitis
GianlucaRompianesi1,AngusHann2,OluyemiKomolafe3,StephenPPereira4,BrianRDavidson5,KurinchiSelvanGurusamy5
1International Doctorate SchoolinClinical andExperimentalMedicine, University of Modena andReggio Emilia,Modena, Italy.
2RoyalFreeHospital,London,UK.3UniversityCollegeLondon,London,UK.4UCLInstituteforLiverandDigestiveHealth,Royal
FreeHospitalCampus,London,UK.5DepartmentofSurgery,RoyalFreeCampus,UCLMedicalSchool,London,UK
Contactaddress:KurinchiSelvanGurusamy,DepartmentofSurgery,RoyalFreeCampus,UCLMedicalSchool,PondStreet,London,
NW32QG,[email protected].
Editorialgroup:CochraneUpperGIandPancreaticDiseasesGroup.
Publicationstatusanddate:New,publishedinIssue4,2017.
Citation: Rompianesi G, Hann A,Komolafe O, Pereira SP,Davidson BR, Gurusamy KS.Serumamylase and lipase and urinary
trypsinogenandamylasefordiagnosisofacutepancreatitis.CochraneDatabaseofSystematicReviews2017,Issue4.Art.No.:CD012010.
DOI:10.1002/14651858.CD012010.pub2.
Copyright©2017TheCochraneCollaboration.PublishedbyJohnWiley&Sons,Ltd.
ABSTRACT
Background
The treatment of people with acute abdominal pain differs if they have acute pancreatitis. It is important to know the diagnostic
accuracyofserumamylase,serumlipase,urinarytrypsinogen-2,andurinaryamylaseforthediagnosisofacutepancreatitis,sothatan
informeddecisioncanbemadeastowhetherthepersonwithabdominalpainhasacutepancreatitis.ThereiscurrentlynoCochrane
reviewofthediagnostictestaccuracyofserumamylase,serumlipase,urinarytrypsinogen-2,andurinaryamylaseforthediagnosisof
acutepancreatitis.
Objectives
Tocompare thediagnostic accuracyofserumamylase,serumlipase,urinary trypsinogen-2, andurinary amylase,eitheraloneorin
combination,inthediagnosisofacutepancreatitisinpeoplewithacuteonsetofapersistent,severeepigastricpainordiffuseabdominal
pain.
Searchmethods
WesearchedMEDLINE,Embase,ScienceCitationIndexExpanded,NationalInstituteforHealthResearch(NIHRHTAandDARE),
and other databases until March 2017. We searched the references of the included studies to identify additional studies. We did
notrestrictstudiesbasedonlanguage orpublicationstatus,orwhetherdatawerecollectedprospectivelyorretrospectively.Wealso
performeda’relatedsearch’and’citingreference’searchinMEDLINEandEmbase.
Selectioncriteria
Weincludedallstudiesthatevaluatedthediagnostictestaccuracyofserumamylase,serumlipase,urinarytrypsinogen-2,andurinary
amylaseforthediagnosisofacutepancreatitis.Weexcludedcase-controlstudiesbecausethesestudiesarepronetobias.Weaccepted
anyofthefollowingreferencestandards:biopsy,consensusconferencedefinition,radiologicalfeaturesofacutepancreatitis,diagnosis
ofacutepancreatitisduringlaparotomyorautopsy,andorganfailure.Atleasttworeviewauthorsindependentlysearchedandscreened
thereferenceslocatedbythesearchtoidentifyrelevantstudies.
Serumamylaseandlipaseandurinarytrypsinogenandamylasefordiagnosisofacutepancreatitis(Review) 1
Copyright©2017TheCochraneCollaboration.PublishedbyJohnWiley&Sons,Ltd.
Datacollectionandanalysis
Tworeviewauthorsindependentlyextracteddatafromtheincludedstudies.Thethresholdsusedforthediagnosisofacutepancreatitis
variedinthetrials,resultinginsparsedataforeachindextest.Becauseofsparsedata,weused-2loglikelihoodvaluestodetermine
which model touse for meta-analysis. We calculatedand reportedthesensitivity, specificity, post-test probability of apositive and
negativeindextestalongwith95%confidenceinterval(CI)foreachcutoff,buthavereportedonlytheresultsoftherecommended
cutoffofthreetimesnormalforserumamylaseandserumlipase,andthemanufacturer-recommendedcutoffof50mg/mLforurinary
trypsinogen-2intheabstract.
Mainresults
Tenstudiesincluding 5056 participantsmettheinclusion criteriaforthisreviewandassessedthediagnostic accuracy oftheindex
testsinpeoplepresentingtotheemergencydepartmentwithacuteabdominalpain.Theriskofbiaswasunclearorhighforallofthe
includedstudies.Thestudythatcontributedapproximatelytwo-thirdsoftheparticipantsincludedinthisreviewwasexcludedfrom
theresultsoftheanalysispresentedbelowduetomajorconcernsabouttheparticipantsincludedinthestudy.Wehavepresentedonly
theresultswhereatleasttwostudieswereincludedintheanalysis.
Serumamylase,serumlipase,andurinarytrypsinogen-2atthestandardthresholdlevelsofmorethanthreetimesnormalforserum
amylaseandserumlipase,andathresholdof50ng/mLforurinarytrypsinogen-2appeartohavesimilarsensitivities(0.72(95%CI
0.59to0.82);0.79(95%CI0.54to0.92);and0.72(95%CI0.56to0.84),respectively)andspecificities(0.93(95%CI0.66to0.99);
0.89(95%CI0.46to0.99);and0.90(95%CI0.85to0.93),respectively).Atthemedianprevalenceof22.6%ofacutepancreatitis
inthestudies,outof100peoplewithpositivetest,serumamylase(morethanthreetimesnormal),serumlipase(morethanthreetimes
normal),andurinarytrypsinogen(morethan50ng/mL),74(95%CI33to94);68(95%CI21to94);and67(95%CI57to76)
peoplehaveacutepancreatitis,respectively;outof100peoplewithnegativetest,serumamylase(morethanthreetimesnormal),serum
lipase(morethanthreetimesnormal),andurinarytrypsinogen(morethan50ng/mL),8(95%CI5to12);7(95%CI3to15);and8
(95%CI5to13)peoplehaveacutepancreatitis,respectively.Wewerenotabletocomparethesetestsformallybecauseofsparsedata.
Authors’conclusions
Asaboutaquarterofpeoplewithacutepancreatitisfailtobediagnosedashavingacutepancreatitiswiththeevaluatedtests,oneshould
havealowthresholdtoadmitthepatientandtreatthemforacutepancreatitisifthesymptomsaresuggestiveofacutepancreatitis,even
ifthesetestsarenormal.About1in10patientswithoutacutepancreatitismaybewronglydiagnosedashavingacutepancreatitiswith
thesetests,thereforeitisimportanttoconsiderotherconditionsthatrequireurgentsurgicalintervention,suchasperforatedviscus,
evenifthesetestsareabnormal.
The diagnostic performance of thesetestsdecreasesevenfurtherwith theprogression of time,and one should havean evenlower
thresholdtoperformadditionalinvestigationsifthesymptomsaresuggestiveofacutepancreatitis.
PLAIN LANGUAGE SUMMARY
Bloodandurinetestsforthediagnosisofacutepancreatitis(suddeninflammationofpancreas)
Background
Thepancreasisanorganintheabdomen(tummy)thatsecretesseveraldigestiveenzymes(substancesthatbreakdownthefoodweeat)
intothepancreaticductalsystem,whichemptiesintothesmallbowel.ThepancreasalsocontainstheisletsofLangerhans,whichsecrete
severalhormonessuchasinsulin(whichhelpsregulatebloodsugar).Acutepancreatitisissuddeninflammationofthepancreas,which
canleadtodamageoftheheart,lungs,andkidneysandcausethemtofail.Acutepancreatitisusuallymanifestsasupperabdominal
painradiatingtotheback.However,thereareseveralpotentialcausesofupperabdominalpain.Itisimportanttodetermineifsomeone
withabdominalpainhasacutepancreatitisoranotherillnessinordertostartappropriatetreatment.Bloodtestssuchasserumamylase
andserumlipase,aswellasurinetestssuchasurinarytrypsinogen-2andurinaryamylase,canbeusedtodetermineifsomeonewith
abdominalpainhasacutepancreatitis.Itisusuallythecasethatapatientisconsideredtohaveacutepancreatitisonlywhenamylase
orlipaselevelsarethreetimestheupperlimitof normal.Withregardtourinary trypsinogen-2, alevelofmorethan50ng/mLof
trypsinogen-2intheurineisconsideredanindicationofacutepancreatitis.Withregardtourinaryamylase,thereisnoclear-cutlevel
beyondwhichsomeonewithabdominalpainisconsideredtohaveacutepancreatitis.Atpresentitisunclearwhetherthesetestsare
equallyeffectiveorifoneofthetestsisbetterthantheotherinthediagnosisofacutepancreatitisinpeoplewithsudden-onsetabdominal
Serumamylaseandlipaseandurinarytrypsinogenandamylasefordiagnosisofacutepancreatitis(Review) 2
Copyright©2017TheCochraneCollaboration.PublishedbyJohnWiley&Sons,Ltd.
pain.Wedeterminedtoresolvethisquestionbyperformingaliteraturesearchforstudiesreportingtheaccuracyoftheabovementioned
bloodandurinetests.Weincludedstudiesreporteduntil20March2017.
Studycharacteristics
We identified 10 studies reporting information on 5056 people with abdominal pain that started suddenly. The studies included
pancreatitisduetoallcauses.
Qualityofevidence
Allofthestudieswereofunclearorlowmethodologicalquality,whichmayresultinarrivingatfalseconclusions. Weexcludedthe
studythatcontributedapproximatelytwo-thirdsoftheparticipantsincludedinthisreviewfromtheresultsoftheanalysispresented
belowduetoconcernsaboutwhethertheparticipantsincludedinthestudyaretypicalofthoseseenintheemergencydepartment.
Keyresults
Theaccuracy ofserumamylase,serumlipase, andurinary trypsinogen-2 inmaking thediagnosis ofacute pancreatitis wassimilar.
Aboutaquarterofpeoplewithacutepancreatitisfailtobediagnosedashavingacutepancreatitiswiththesetests.Thepatientshould
beadmittedandtreatedashavingacutepancreatitis,evenifthesetestsarenormal,ifthereisasuspicionofacutepancreatitis.Asabout
1in 10 patients without acute pancreatitis may be wrongly diagnosed ashaving acute pancreatitis with thesetests, itis important
toconsider otherconditions thatrequireurgentsurgery,evenifthesetestsareabnormal.Thediagnostic performanceofthesetests
decreasesevenfurtherwiththeprogressionoftime,andadditionalinvestigationsshouldbeperformedifthereisasuspicionofacute
pancreatitis.
• Acuteonsetofapersistent,severeepigastricpainoften
BACKGROUND
radiatingtotheback.
Thepancreasisanabdominalorganthatsecretesseveraldigestive
• Serumlipaseactivity(oramylaseactivity)atleastthree
enzymes into the pancreatic ductal system, which empties into
timesgreaterthantheupperlimitofnormal.
the small bowel. It also houses the islets of Langerhans, which
secreteseveralhormonesincluding insulin(NCBI2014).Acute • Characteristicfindingsofacutepancreatitisoncontrast-
pancreatitisisasuddeninflammatoryprocessinthepancreas,with enhancedcomputedtomography(CECT)and,lesscommonly,
variable involvement of adjacent organs or other organ systems magneticresonanceimaging(MRI)ortransabdominal
(Bradley1993).Theannualincidenceofacutepancreatitisranges ultrasonography.
from5to30per100,000population(Roberts2013;Yadav2006).
Inthelastone totwodecadestherehasbeenanincreaseinthe Acute pancreatitis can be classified into interstitial oedematous
incidenceofacutepancreatitisintheUKandUSA(Roberts2013; pancreatitis (diffuseoroccasionally localisedenlargementof the
Yang2008).Acutepancreatitisisthemostcommongastrointesti- pancreasduetoinflammatoryoedemaasseenonCECT)ornecro-
nal(digestivetract)causeofhospitaladmissionintheUSA(Peery tisingpancreatitis(necrosisinvolvingeitherthepancreasorperi-
2012).Gallstonesand alcoholare thetwo maincauses of acute pancreatictissues,orboth)(Banks2013).Approximately90%to
pancreatitis.Approximately50%to70%ofcasesofacutepancre- 95% of people with acute pancreatitis have interstitial oedema-
atitisarecausedbygallstones(Roberts2013;Yadav2006).Increas- touspancreatitis,whiletheremainderhavenecrotisingpancreati-
ingage,malegender,andlowersocioeconomicclassareassociated tis (Banks 2013). Necrotising pancreatitis may be sterile or in-
withahigherincidenceofacutepancreatitis(Roberts2013). fected(Banks2013).Varioustheoriesexistastohowpancreatic
and peripancreatic tissues become infected, including spreading
Accordingtoaconsensusconferenceontheclassificationofacute oftheinfectionfrombloodcirculation,lymphatics,bile,fromthe
pancreatitis,thediagnosisofacutepancreatitisisgenerallymade smallbowel(duodenum)throughthepancreaticduct,andmigra-
whenatleasttwoofthefollowingthreefeaturesarepresent(Banks tionthroughthelargebowelwall(translocation)(Schmid1999).
2013).
Localcomplications ofacutepancreatitisincludeacuteperipan-
creaticfluidcollection,pancreaticpseudocyst,acutenecroticcol-
Serumamylaseandlipaseandurinarytrypsinogenandamylasefordiagnosisofacutepancreatitis(Review) 3
Copyright©2017TheCochraneCollaboration.PublishedbyJohnWiley&Sons,Ltd.
lection,andwalled-offnecrosis(Banks2013).Thesystemiccom- normallevelsoverthenext5to7days(Vissers1999).Acommon
plicationsofacutepancreatitisincludeworseningofpre-existing thresholdusedisthreetimesthenormallimit(Banks2013).
illnesses,suchasheartorchroniclungdisease(Banks2013).The
mortalityratefollowinganattackofacutepancreatitisisbetween
6% and 20% (Roberts 2013; Yadav 2006). The mortality rate Serumlipase
dependsupontheseverityofacutepancreatitisandthepresence Lipaseisanotherenzymesecretedbythepancreas.Acutepancre-
ofinfection.Acutepancreatitiscanbeclassifiedasmild,moder- atitisisthemainreasonforanincreaseinlipase,althoughanum-
ate,orsevere,dependinguponthepresenceoflocalorsystemic berofotherconditionssuchaschronicpancreatitis,acutechole-
complications, transient organ failure involving one of more of cystitis,andbowelobstructioncanincreaselipaseactivity(Vissers
lungs,kidneys,andcardiovascularsystem(heartandbloodvessels) 1999).Inacutepancreatitis,serumlipaselevelsusuallyrisewithin
lasting up to 48 hours, or persistent failure of the same organs 4to8hours, peakat24hours, and decreasetonormal or near
mentionedabovelastingbeyond48hours.Inmildpancreatitis, normal levelsover the next 8 to 14 days. Serumlipase remains
therearenolocalcomplications,systemiccomplications,ororgan elevated for a longer period of time compared to the period of
failure.Inmoderatelysevereacutepancreatitis,theremaybelo- elevationofserumamylaseafteracutepancreatitis(Vissers1999).
calorsystemiccomplicationsortransientorganfailure.Insevere Acommonthresholdusedisthreetimesthenormallimit(Banks
acutepancreatitis,thereispersistentorganfailure(Banks2013). 2013).
(See summary in Table 1.) Acute severe pancreatitis carries the
worstprognosisintermsofmortality,whilemildpancreatitishas
thebestprognosis(Banks2013).Infectednecrotisingpancreatitis Urinarytrypsinogenlevel
carriesasignificantlyworseprognosisthansterilenecrotisingpan-
Autodigestion because of trypsinogen activation is one of the
creatitis,withanaveragein-hospitalmortalityofmorethan30%
mechanismsbelievedtoresultinacutepancreatitis.Sincetrypsino-
forpeoplewithinfectednecrotisingpancreatitis,whichincreases
gen levels are elevated in acute pancreatitis, measurement of
tomorethan40%inthesubgroupofpeoplewithorganfailurein
urinary trypsinogen-2 (an isoenzyme of trypsinogen) has been
additiontoinfection(Petrov2010).
proposed as a test for diagnosing pancreatitis (Hedstrom 1994;
SeeAppendix1foraglossaryofterms. Hedstrom1996;Hedstrom1996c).Inacutepancreatitis,urinary
trypsinogen levelsusually rise to high levelswithin afew hours
anddecreaseinthreedays(Matull2006).Acommonthreshold
Targetconditionbeingdiagnosed usedis50ng/mL(Chang2012).
Acutepancreatitisinpeoplewithacuteepigastricpainordiffuse
abdominalpain.
Urinaryamylase
Urinaryamylaseabove2000IU/Lisconsideredabnormal.Mea-
surementofurinary amylasehasbeenproposedasatestforthe
Indextest(s)
diagnosisofpancreatitis(Hedstrom1996c;Kemppainen1997c).
Alloftheindextestsevaluatedinthisreviewareperformedbythe
laboratorytechnicianandinterpretedbytheclinician.
Clinicalpathway
Serumamylase Forpeoplewithacuteonsetofapersistent,severeepigastricpain
Amylaseisanenzymesecretedbythepancreas.Variousothertis- or with diffuse abdominal pain starting in the epigastric region
suesincludingsalivaryglands,smallintestine,ovaries,adiposetis- (orifthepersonisunsureabouttheregioninwhichdiffuseab-
sue, and skeletal muscles secrete amylase. There are two major dominalpainbegan),clinicalexaminationincludingrecordingof
isoformsofamylase:pancreaticamylaseandsalivaryamylase.The bloodpressure,pulserate,andoxygensaturations(whenavailable)
normalrangeofamylasevariesbetweenlaboratories,butisusu- areperformed.Routinebloodtestssuchasfullbloodcount,urea,
allybetween100internationalunits(IU)/Lto300IU/L(Vissers creatinine,andelectrolytesarealsoperformed.Bloodtestssuchas
1999).Acutepancreatitisisonecauseofincreasedamylase(hyper- amylaseandlipase(indextestsbeingevaluatedinthisreview)are
amylasaemia). Thereasonforthiselevationisunclear,although performedtoconfirm(orruleout)thediagnosisofacutepancre-
capillary leakage due to obstruction of venous and lymphatic atitis.Radiologicalfindingsofacutepancreatitisevolveoverafew
drainage of pancreatic and peripancreatic tissues, and transperi- daysandtheradiologicalfeaturesmaynotbeapparentintheearly
tonealabsorptionofamylasemayberesponsible(Vissers1999). stages,ormayevenbenormal(Banks2013;Vissers1999),thus
In acute pancreatitis, serum amylase levelsusually rise within 6 onecannotrelyonradiologicalteststodiagnoseacutepancreatitis,
to 24 hours, peak at 48 hours, and decrease to normal or near atleastintheearlystages.RadiologicalexaminationwithCTscan
Serumamylaseandlipaseandurinarytrypsinogenandamylasefordiagnosisofacutepancreatitis(Review) 4
Copyright©2017TheCochraneCollaboration.PublishedbyJohnWiley&Sons,Ltd.
or MRI is not routinely performedif a diagnosis of acute pan- tive protein routinely todetermine whetherpatients require ra-
creatitisissuspected.Ifacutepancreatitiscanberuledout,other diologicalinvestigationstodiagnosenecrotisingpancreatitis.Fre-
causesofacuteepigastricpainshouldbeconsidered.Pepticulcer, quently,therising trendinC-reactiveprotein,procalcitonin, or
functionaldyspepsia,andgallstonescanpresentwithacuteepigas- lactate dehydrogenase, ratherthana single test,may be usedto
tricpain(Gurusamy2014;Moayyedi2006).Allofthesealterna- determinewhetherpatientsrequireradiologicalinvestigationsto
tivecausesofepigastricpainaregenerallyinvestigatedandtreated diagnosenecrotisingpancreatitis.ItmustbenotedthatCTscan
afterdischargeofthepatientunlessthereisastrongsuspicionof or MRI is not routinely performed during the initial stages of
perforatedpepticulcer,usuallybecauseoffeaturesofperitonitis acutepancreatitis,butusuallyinthepresenceoforganfailureor
orbecausepaincontrolcouldnotbeachieved.Insuchinstances, becauseoftheresultsoftheserumC-reactiveprotein.Thevarious
eithera plain X-ray of theabdomen or emergency CT scan, or treatmentstrategiesforacutenecrotisingpancreatitisincludenon-
bothmaybeperformedtoidentifythepresenceoffree-intraperi- surgical (conservative) treatment, percutaneous drainage, endo-
tonealgas(Ghekiere2007;Grassi2004).Theusualtreatmentfor scopictransluminaldrainage,earlysurgicaldebridement(necro-
perforatedpepticulcerisemergencysurgical closure,whichcan sectomy, which can be performed by open surgery or by min-
beperformedbyopenorlaparoscopicsurgery(Sanabria2013). imally invasive retroperitoneal debridement), delayed necrosec-
Ifadiagnosisofacutepancreatitiscanbeestablished,usuallybased tomy(delayingthesurgerybyaboutfourweeks),orastep-upap-
ontheconsensuscriteria,thepatientisadmittedtohospitaland proachthatconsistsofendoscopicorpercutaneousdrainagefol-
theseverityofpancreatitisisassessed.Thetreatmentofacutepan- lowedby laparoscopicnecrosectomy ifrequired, and non-surgi-
creatitisisgenerallysupportivetreatment,thatismaintenanceof cal(conservative)treatment(Bakker2012;Mouli 2013;Tenner
fluid and electrolyte imbalance. Despite various pharmacologi- 2013; vanBrunschot 2014; van Santvoort 2010;van Santvoort
cal interventions being evaluated in acute pancreatitis, none is 2011).ArecentCochranesystematicreviewfoundthatastep-up
currentlyrecommendedastreatment.Abdominalultrasoundand approachmaybepreferabletodirectsurgeryinparticipantswith
magneticresonancecholangiopancreatographyorendoscopicul- acutenecrotisingpancreatitis(Gurusamy2016).Allofthesetreat-
trasoundmaybeperformedtoinvestigatetheaetiologyofacute mentsaresupportedbyappropriatefluidtherapyandnutritional
pancreatitis.Inthepresenceofgallstones,cholecystectomyisper- support.Thisisincomparisonwithsevereacuteoedematouspan-
formed. The timing of cholecystectomy in acute pancreatitis is creatitis,wherethemaintreatmentissupportivetreatmentforsys-
controversial, and different factors must be considered depend- temiccomplications,includingorganfailureandtreatmentoflocal
ingupontheseverityofacutepancreatitis(Gurusamy2013).En- complicationssuchaspseudocystifsymptomatic(Cannon2009;
doscopicsphincterotomyorcommonbileductexplorationmay Cheruvu2003;Johnson2009;Varadarajulu2008;Varadarajulu
havetobeperformedinthepresenceofcommonbileductstones 2013). Ifpatients haveinfectedpancreatic necrosis, appropriate
(Ayub2004;Larson2006).Intheabsenceofgallstones,investi- antibioticsareadministeredinadditiontothetreatmentoutlined
gation of other causes of acute pancreatitis is required. Patients abovefornon-infectedpancreaticnecrosis.Ifpatientshaveacute
are generally monitored clinically. If the patient improves clini- peripancreaticcollectionsorpseudocystsontheradiologicaltests,
callywith supportive treatment, the patientwith gallstone pan- clinicalandradiologicalfollow-uparerequiredtoensureresolu-
creatitisisdischargedaftercholecystectomyorafterschedulinga tionofthesecollections.
cholecystectomyoronaplannedlist,withintwoweeks.Forthose Ifthediagnosisofacutepancreatitiscannotberuledoutontheba-
patientswithsevereacutepancreatitis,cholecystectomyisunder- sisoftheclinicalpresentationandserumamylaseorlipase,thepa-
takenwhenclinicallyappropriateafterresolutionofpancreatitis. tientisadmittedtohospitalandtheevolutionofsignsandsymp-
Ifthepatientdeterioratesclinically,thepatientundergoesaCT tomsisnoted.Serumamylaseandlipasemayberepeatedorradi-
scan and may require high-dependency or intensive care in the ologicalexaminationsmaybeperformedtoestablishorruleout
presenceoforganfailureorinfectedpancreaticnecrosis. acutepancreatitiswithareasonableamountofcertainty.Testsfor
Inthepresenceoforgan failure,patientsundergo aCTscan or organfailure(e.g.ureaandcreatinineforidentifyingrenalfailure,
MRItoidentifyanylocalcomplications.C-reactiveprotein,pro- bloodpressure,pulserate,respiratoryrate,urineoutput,andarte-
calcitonin,andlactatedehydrogenasemightdistinguishbetween rialbloodgases)mayalsobeperformedtoensurethatthepatient
oedematousandnecrotisingpancreatitis(Alfonso2003;Khanna doesnothavemoderatelysevereorseverepancreatitisirrespective
2013; Rau 1998), andcould potentially be used asatriage test of theresultsof serumamylaseandlipase. Thepossible clinical
to identify patients who need furtherradiological tests in those pathwayinthediagnosisandmanagementofacutepancreatitisis
withoutorgan failure(Alfonso2003).Somecentresuse C-reac- showninFigure1.
Serumamylaseandlipaseandurinarytrypsinogenandamylasefordiagnosisofacutepancreatitis(Review) 5
Copyright©2017TheCochraneCollaboration.PublishedbyJohnWiley&Sons,Ltd.
Figure1. Clinicalpathway.Footnotes:Acutepancreatitisisusuallyconfirmedbyconsensuscriteria(Banks
2013).Irrespective oftheCTscanfindingsandpresenceorabsenceofnecrosis,patientswithorganfailurewill
requireorgansupportandwillreceiveaCTscan.CTscanmayalsobeperformedinpeoplewithoutorgan
failureifthereisclinicaldeterioration(notamountingtoorganfailure)orinsomecentresbasedonan
elevatedCRP.NecrotisingpancreatitisisusuallyconfirmedbythefindingsontheCTscanandby
histopathologicalexaminationofthebiopsyobtainedduringnecrosectomyifearlynecrosectomyis
performed.InfectednecrotisingpancreatitisisusuallyconfirmedbythefindingsontheCTscanandby
microbiologicalexaminationoffluidaspiratedunderradiologicalguidanceorfromthetissuebiopsyobtained
duringnecrosectomyifearlynecrosectomyisperformed.Organfailureisdiagnosedonthebasisofclinical
examinationandbloodtests(urea,creatinine,bloodpressure,pulserate,respiratoryrate,arterialbloodgas
analysis).Abbreviations:CRP:C-reactiveproteinCT:computedtomographyEUS:endoscopicultrasoundMRCP:
magneticresonancecholangiopancreatography
Serumamylaseandlipaseandurinarytrypsinogenandamylasefordiagnosisofacutepancreatitis(Review) 6
Copyright©2017TheCochraneCollaboration.PublishedbyJohnWiley&Sons,Ltd.
Priortest(s)
usedinthediagnosisofacutepancreatitis.Itisimportanttoun-
Theminimumpriortestthatisperformedbeforethesetestsare derstandthediagnosticaccuracyofthesetests.Urinarytrypsino-
conductedisclinicalhistoryandclinicalexamination,whichin- genandamylasehavebeeninvestigatedasalternatetests,anditis
cludesobtainingthebodytemperature,heartrate,bloodpressure, importanttounderstandwhethertheycanreplaceserumamylase
respiratoryrate,andpulseoximetry(whenavailable). andlipaseinthediagnosisofacutepancreatitis.Ifoneormoreof
thetestsbeingassessedhasahighdegreeofaccuracy,patientswith
acute pancreatitis can be identified and managed appropriately.
Roleofindextest(s) Atthesametime,unnecessaryhospitaladmissionforobservation
Theindextestsareusedforthediagnosisofacutepancreatitisin canbeavoidedinpatientswithoutacutepancreatitis,resultingin
peoplewithacuteonsetofapersistent,severeepigastricpainor considerableresourcesavings.Therehasbeennosystematicreview
withdiffuseabdominalpainthatstartedintheepigastricregion andmeta-analysisofthediagnosticaccuracyofserumlipaseand
(orifthepersonisunsureabouttheregioninwhichdiffuseab- amylaseactivityorurinaryamylaseinthediagnosisofacutepan-
dominal pain began). The current testsused are serumamylase creatitis.Thecurrentconsensuscriteriaaboutdiagnosisofacute
and serum lipase. Urinary trypsinogen and urinary amylase are pancreatitisincludedserumlipaseoramylaseactivityatleastthree
beingevaluatedasreplacementtestsforserumamylaseandserum times greater than the upper limit of normal as one of the cri-
lipase. teriafordiagnosis ofacutepancreatitis(twoofthethreecriteria
mustbemet,theothertwobeingacuteabdominalpainandimag-
ing characteristic of acute pancreatitis) (Banks 2013). However,
Alternativetest(s) these criteria are based on consensus rather than on systematic
reviews.Inaddition,thethresholdforamylaseorlipasemayneed
Other tests used in the diagnosis of acute pancreatitis include
toberevisedfromthreetimesnormaltoadifferentthresholdif
serumtrypsinogen-2(Hedstrom1994),andradiologicaltestssuch
thesetestsare accurate atdifferentthresholds.Ifthissystematic
ascontrast-enhancedcomputedtomography(CECT),magnetic
review found thaturinary amylase or trypsinogen-2 werebetter
resonance imaging (MRI), or transabdominal ultrasonography
thanserumamylaseorlipase,thecriteriaforthediagnosisofacute
(Banks2013).Otherbiomarkerssuchasserumtrypsin-2-alpha1-
pancreatitiswouldneedtobealtered.Therehavebeentwosystem-
antitrypsincomplex,carboxypeptidaseBactivationpeptide(CA-
aticreviewsonthediagnostictestaccuracyofurinarytrypsinogen-
PAP), and urinary trypsinogen activation peptide (TAP) have
2inthediagnosisofacutepancreatitis(Chang2012;Jin2013).
beenevaluatedasdiagnostictestsforacutepancreatitis(Hedstrom
Inbothreviews,languagerestrictions(EnglishandChinese)were
1996d;Saez2005),butthesearenotinroutineuseforthediag-
present.Thesearcheswereperformedin2011and2012,respec-
nosisofthiscondition.
tively.Onlyoneofthereviewsusedappropriatestatisticalanalysis
(Chang2012).TherehasbeennoCochranereviewontheroleof
Rationale urinarytrypsinogen-2inthediagnosisofacutepancreatitis.The
change in diagnostic accuracy of these tests with different time
Inadditiontoacutepancreatitis,thereareseveralothercausesof
intervalsfrompresentationhasnotbeenpreviouslyassessedina
epigastricpainincluding pepticulcer,functional dyspepsia,and
systematicreview.ACochranesystematicreviewofthediagnostic
gallstones (Gurusamy 2014; Moayyedi 2006). Of these various
test accuracy of serumand urine tests in the diagnosis of acute
causes,peoplewithacutepancreatitisandperforatedpepticulcer
pancreatitiswas,therefore,necessary.
need emergency admission and treatment, while others may be
discharged if pain control can be achieved. Itis thusimportant
to make a diagnosis of acute pancreatitis. Radiological findings
ofacutepancreatitisevolveoverafewdays,andtheradiological
examination may not demonstrate characteristic features in the
earlystages,ormayevenbenormal(Banks2013;Vissers1999),
thusradiologicaltestsarenotroutinelyperformedfordiagnosing OBJECTIVES
thiscondition. In addition, acute pancreatitis can mimic perfo-
rated peptic ulcer (Kuzmich 2012), which is usually treated by Tocomparethediagnosticaccuracyofserumamylase,serumli-
surgery.Correctdiagnosisofacutepancreatitiscanavoidunneces- pase,urinarytrypsinogen-2,andurinaryamylase,eitheraloneor
sarysurgery.Hence,anaccuratediagnostictestforthediagnosisof incombination, in thediagnosis of acute pancreatitis in people
acutepancreatitisisessentialinpeoplewithsuspectedacutepan- withacuteonsetofapersistent,severeepigastricpainordiffuse
creatitis.Serumamylaseandlipasearethetestsmostcommonly abdominalpain.
Serumamylaseandlipaseandurinarytrypsinogenandamylasefordiagnosisofacutepancreatitis(Review) 7
Copyright©2017TheCochraneCollaboration.PublishedbyJohnWiley&Sons,Ltd.