patellar and achilles tendinopathy - diva...

Department of Surgical and Perioperative Sciences, Sports Medicine

Umeå University SE-901 87 Umeå

Patellar and Achilles tendinopathy

Sclerosing injections and ultrasound guided arthroscopic shaving

Lotta Willberg

Copyright © Lotta Willberg 2013

Cover and cover sheets, photo is published with the kind permission of the JK patient

and dancer Robin “Tumpum” Peters Fernström. Original photo taken by Ida Nyström.

Layout and processing of the photo made by the author and Anneli Falck, TMG Stockholm

All MRI, US/CD images are provided and processed by the author and are published with

the permission of the patients included in the studies of this thesis.

Figure 2 and 3 on page 19, Anneli Falck, TMG Stockholm

Photos 1-3 on page 21, taken by the author

Photos 4-6 on page 43-44, taken by Dan Friberg at the Capio Artroclinic AB, Stockholm,

Sweden

All previously published papers were reproduced with the kind permission of the publishers.

Responsible publisher under Swedish law: the Dean of the Medical Faculty

This work is protected by the Swedish Copyright Legislation (Act 1960:729)

ISSN: 0346-6612

New series no: 1585

ISBN 978-91-7459-696-0

Electronic version available at http://umu.diva-portal.org/

Printed by: TMG Sthlm AB, Bromma 2013

Stockholm, Sweden 2013

Capio Artroclinic AB, Stockholm, Sweden provided all clinical resources throughout

the whole process of this thesis.

Study V was partially funded by the Swedish National Centre for Research in Sports.

To conquer oneself is a greater victory than to conquer thousands in a battle

Dalai Lama

To my beloved family; Tommy, Emil and Fia.

And to my mother and my late father.

4 Lotta Willberg | Patellar and Achilles tendinopathy

Table of Contents

Abstract 7List of original papers 8Abbreviations 9Summary of thesis in Swedish 10Introduction 13 The normal tendon 14 The Achilles tendon 17 The patellar tendon 19 TheHoffa’sfatpad 21Background 23 Epidemiology 24 Aetiology 25 Histopathology 25 Clinicalsymptomsandfindings 26 X-rayandMRI 27 UltrasoundandcolourDoppler 28 Treatmentmethods 29Definitions 33Aims and hypothesis 37Materials and methods 39 Subjects 40 Inclusion and exclusion criterias 41 Diagnostics in this thesis 41 Treatmentmethodsinthisthesis 42 Outcomemeasures 46 Ethicalconsiderations 46 Statistics 47Summary of papers 49

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Discussion 59 Generaldiscussionandclinicalconsiderations 60 MidportionAchillestendinopathy 61 Patellartendinopathy 62 Genderandtendons 65 US/CDfindings 66 Finalreflections 68 Strengthsandlimitations 69Conclusion 71Acknowledgements 73References 76Papers I-V 89

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AbstractChronic painful tendinopathy is a common cause for elite- and recreational athletes tostopordecreasetheleveloftheirsportsactivity.Recentresearchoninnervationpatterns,histopathology and possible pain mechanisms in tendons has led to an increased knowledge aboutthechronicpainfultendon.Ultrasound(US)andcolourDoppler(CD)examinationshowing localized high blood flow, inside and outside regions with structural tendonabnormalities,hasbeenshowntobeofimportancefortendonpain.Immunohistochemicalanalysesofbiopsieshaveshownsensoryandsympatheticnervesincloserelationtothehighbloodflowinthepainfulregionofthetendon.Thesefindingshaveledtonewideasaboutdevelopmentofnewtreatmentmethodsforchronicpainfultendinopathy.In study I, we evaluated the already in use, US-guided sclerosing polidocanol injectiontreatmentofmidportionAchillestendinopathy,usingtwodifferentconcentrationsofthesubstance.Thisstudyaimedtofindoutiftherewasafasterreturntopainlessactivitybyusingtheconcentration10mg/mlcomparedtotheformerlyused5mg/ml.Therewerenosignificantdifferencesintheclinicalresultsbetweenthegroups.InstudyII-technicalnote,weaimedtodevelopanewone-stagesurgicaltreatmentmethodforpatellartendinopathy.ThismethodwasbasedonresearchconcerningtheinnervationpatternsandUS/CDfindingsinpatellar tendinopathy/ “jumper’sknee”.Technicallyweaddedultrasoundguidance tokneearthroscopytoidentifyandvisualizetheregionofinterestduringasurgicalshavingprocedure.InstudyIII,wetestedthenewlyinventedUS/CD-guidedarthroscopicshavingtechniqueinapilotstudy.Theshort-termclinicalresultswerepromisingandthemajorityof thepatients returned topainless activity after a short rehabilitationperiod. In studyIV,wecomparedtheUS/CD-guidedartrhroscopicshavingmethodwiththealreadyinusesclerosingpolidocanolinjectiontreatmentinarandomizedstudy.Atshort-termfollow-up,the patients treatedwithUS/CD-guided arthroscopic shavinghad significantly less painduring rest and activity,were significantlymore satisfiedwith the treatment, andhad afasterreturntosports,comparedto thepatients in thesclerosing injectiongroup.Therewerenocomplications.InstudyV,at longer-termfollow-up(endpoint46months)therewasasignificantdecreaseinpainduringactivityinbothgroups.Therewerenoremainingsignificantdifferences in thepain levelsduring activitybetween the groups.The tendonstructurehad improvedsignificantly inbothgroups. Therewasasignificantdecrease intheanteroposteriorthicknessoftheproximalpatellartendoninpatientstreatedwithUS/CD-guidedarthroscopicshaving,butnotinthesclerosinginjectiongroup.TheCDflowhaddiminishedsignificantlyinbothgroups,andtherewasacorrelationbetweenlowCDflowandhighpatientsatisfactioninbothgroups.TheCDflowdecreasedfasterinthesurgicalgroup than in the injection group. In conclusion, this newly invented US/CD-guidedarthroscopicshavingtreatment,focusingontreatmentoutsidethetendon,hasshowngoodclinicalresultswithpainreliefandafastreturntosportsactivity,inpatientswithpatellartendinopathy.

Keywords:arthroscopy,jumper’sknee,sclerosinginjection,tendinopathy,ultrasound


LIST OF ORIGINAL PAPERS Thisthesisisbasedonthefollowingstudies

I. Sclerosing injections to treat midportion Achilles tendinosis: arandomisedcontrolledstudyevaluatingtwodifferent concentrations of Polidocanol WillbergLotta,SundingKerstin,ÖhbergLars,ForssbladMagnus, FahlströmMartin,AlfredsonHåkan Knee Surg Sports Traumatol Arthrosc (2008) 16:859–864

II. Ultrasound- and Doppler-guided arthroscopic shaving to treat Jumper’s knee: a technical note WillbergLotta,SundingKerstin,ForssbladMagnus,AlfredsonHåkan Knee Surg Sports Traumatol Arthrosc (2007) 15:1400–1403

III. Treatment of Jumper´s knee: promising short-term results in a pilot study using a new arthroscopic approach based on imagingandhistologicalfindings WillbergLotta,SundingKerstin,ÖhbergLars,ForssbladMagnus, AlfredsonHåkan Knee Surg Sports Traumatol Arthrosc (2007) 15:676–681

IV. Sclerosing polidocanol injections or arthroscopic shaving to treat patellar tendinopathy/jumper´s knee? A randomised controlled study WillbergLotta,SundingKerstin,ForssbladMagnus,FahlströmMartin, AlfredsonHåkan Br J Sports Med 2011;45:411–415

V. Treatment of patellar tendinopathy with sclerosing injections or ultrasound-guided arthroscopic shaving -alongtermfollow-upofultrasoundfindingsand clinical results SundingKerstin,WillbergLotta,WernerSuzanne,AlfredsonHåkan, ForssbladMagnus,FahlströmMartin Manuscript submitted 2013

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Abbreviations

ADL activityofdailylivingAP anteroposteriorBMI body mass indexCD colourDopplercm centimetersCSA cross sectional areaESWT extracorporeal shock wave therapyGAG glucose amino glycanesGS greyscaleHFP Hoffa’sfatpadIFP infrapatellarfatpadJK jumper’skneeKg kilogramskN kiloNewtonm. musculusMRI magnetic resonance imagingNP neuropeptidesNSAID nonsteroidalanti-inflammatorydrugPD power DopplerPGP9.5 proteingeneproduct9.5PRP platelet-rich plasma injectionPT patellar tendonRCT randomized controlled trialROM rangeofmotionSD standard deviationSP substance PSPSS StatisticalPackagefortheSocialScienceUS ultrasoundVAS visual analogue scaleVMO vastus medialis obliquusX-ray plainfilmradiography


Kronisk smärtande patellar- och Achillessena Skleroserande injektioner och ultraljudsvägledd artroskopisk kirurgi

Bakgrund Den kroniskt smärtande senan är en vanlig orsak till att motionärer och elitaktiva idrottare tvingas minska eller avsluta sitt idrottande. Kronisktsmärtande patellarsena (knäskålssena), sk hopparknä, är en diagnos som ärsvårbehandladochiblandävensvårattdiagnosticera.IAchillessenan(hälsenan)är sk kroniskt smärtande mittportions tendinos en relativt vanlig åkomma,vilkenkanomöjliggöramotionsutövandepgasmärta.Påsenaretidharforskninggenomförtsavseendehursenorärinnerverade(nervförsörjda)ochhurdebetersigmikrosokopiskt (på cellnivå).Detta har förtydligat och ökat förståelsen fördenkronisktsmärtandesenan.Ökatblodflödeutanförochinutidetsmärtandeområdetverkarvaraavbetydelseförsmärtaochfunktion.DettakansynliggörasmedultraljudochfärgDoppler.Sensoriskaochsympatiskanerverharåterfunnitsinärhetenavdetsmärtandeområdetisenan,somvidanalyseruppvisarettökatblodflöde.DessaupptäckterharletttilltankaromattutvecklabättrediagnostiskametoderochnyamerspecifiktriktadebehandlingsmetoderavsåvälAchillessenasom patellarsena. Det finns också ett behov av att utvärdera behandlingarnagenom att studera hur senan, smärta och funktion förändras över tid efterbehandling.

Mål I delstudie I ville vi utvärdera den ultraljudsledda injektionsbehandlingen,gällande mittportions tendinos i hälsenan, genom att jämföra två olikakoncentrationeravdenskleroserandesubstansenpolidocanol.Avsiktenvarattundersökaomdubblakoncentrationenavsubstansen,jämförtmeddentidigareanvända,kundemedföraenhalveringavantaletbehövdainjektioner.Delstudie2syftadetillattutförasimultantultraljudvidknäartroskopi(titthålskirurgi)förattkunna synliggöra det smärtande området i senan och precisera den artroskopiska åtgärdensålångtdetärmöjligtvidskhopparknä.Vidnormalknäartroskopikanman inte se det smärtande området i patellarsenan. Vidareutveckling av denultraljudsvägledda artroskopin skulle kunna möjliggöra kirurgisk behandling vid skhopparknäochdärmedsannoliktunderlättaförsnabbareåtergångiidrottänvadtidigarebehandlingsmetoderkunnattillåta(delstudie3).Avslutningsvis, var vår föresats att jämföra behandlingsresultaten mellan

denheltnyametoden,ultraljudsvägleddartroskopiochdentidigareexisterandebehandlingsmetoden, skleroserande injektioner med läkemedlet polidocanolhos patientermed sk hopparknä. Avsikten var attmed hjälp av ultraljud och

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färgDopplerstuderahurdensmärtandesenanförändrasövertidefterrespektivebehandlingsmetodochtidentillåtergångismärtfriidrottsutövning(delstudie4,delstudie5).

Metoder I den första delstudien randomiserades (lottades) 47 patienter med 52kroniskt smärtande hälsenor till två grupper. Båda grupperna fick identiskultraljudsvägledd injektionsbehandling med den enda skillnaden att den ena gruppenfick5mg/mlavläkemedletpolidocanolochdenandragruppen10mg/ml.Maximalttrebehandlingargavsibådagrupperna,innanviutvärderadeomdet fanns någon skillnad mellan grupperna avseende effekt på smärta. Såvälpatienten,ortopedspecialistensomultraljudsteknikernvarovetandesomvilkenkoncentrationsomgavsvidolikabehandlingstillfällen.I den tredje delstudien (pilotstudie), fick 15 patienter med hög idrottslig

aktivitetsnivåochmeddiagnosenhopparknä,möjlighetenattgenomgåenriktadkirurgisk behandling med ultraljudsvägledd artroskopi. En helt ny kirurgiskmetoddärvilätultraljudguidaknäartroskopin.Operationenbeskrivsidenandradelstudien. Dessa 15 patienter följdes noggrant efter den ultraljudsvägleddaartroskopiska metoden tills de återgick till smärtfri idrott. I den fjärdedelstudien lottades 45 patienter med 52 kroniskt smärtande patellarsenor,till antingen behandling med ultraljudsvägledd artroskopi eller skleroserande injektionsbehandling med läkemedlet polidocanol. Efter behandlingen följdesdessa patienter över tid. Såväl patienterna från delstudie 4 (45 patienter)som patienterna från delstudie 3 (15 patienter) kallades sedan tillbaka för enlångtidsuppföljningmedutvärderingavsenansutseende(blodflöde,tjocklekochstruktur)medhjälpavultraljudochfärgDopplerundersökningochutvärderingavkliniskabehandlingsresultat(delstudie5).

Resultat i korthet Uppföljningenavpatienterna iden förstadelstudiengjordes igenomsnittefter 14månaderochingasignifikantaskillnaderpåvisadesmellandetvågruppernaavseendesmärta,antalgivnainjektionerellertotaltinjiceradvolymavpolidocanolellerantalnöjdaochsmärtfriapatienter.Eftersomvi ienlighetmedvårhypotes idenandradelstudienkundeidentifieradetsmärtandeområdetmedökatblodflödeipatellarsenan,närvianvändeultraljudsamtidigtmedartroskopi,gickvividaremedpilotstudien(delstudie3).Avde15opereradepatienternahade13efterca6-8veckoråtergåtttillsinidrottmedgottresultatavseendesmärta.Idenfjärdedelstudienvisadedetsigatt de patienter som hade opererats med den ultraljudsledda artroskopiska metoden måddesignifikantbättreochvarsignifikantnöjdarevidkorttidsuppföljningenändepatientersomhadegenomgåttskleroserandeinjektionsbehandling.

12LottaWillberg| Patellar and Achilles tendinopathy

Vid långtidsuppföljningen, efter i genomsnitt 46 månader, uppvisade bådagruppernagodaresultat jämförtmedförestartavbehandling. Däremot fannsinte några kvarvarande skillnader i behandlingsresultat mellan grupperna avseendesmärtavidaktivitet.Senstrukturensågfinareutochdettidigareökadeblodflödethademinskatibådagrupperna.Denendaskillnadenmellangruppernavarsentjockleken,somhademinskatbetydligthosdepatientersomgenomgåttkirurgisk behandling jämfört med de patienter som hade behandlats medskleroserande injektioner.Även sambandsberäkningargjordes, vilka visadeattdettycksfinnasenvisskorrelationmellanlågtblodflödeochhögpatientnöjdhet.

Slutsats Vid behandling av patienter med kroniskt smärtande mittportions tendinos i Achillessenan verkar ultraljudsledda skleroserande polidocanol injektioner vara en framgångsrikmetod förbehandlingavsmärtan.Det tycks intefinnasnågraskillnaderieffektpåsmärtanmellandetvåkoncentrationerna,5och10mg/ml. Vårrekommendationärdärförattvidbehandlingmedskleroserandeinjektionermed polidocanol använda den lägre styrkan och att strikt hålla sig till den ursprungliga metoden, där enbart mycket små volymer (max 2 ml) ges perbehandlingstillfälle.Vidkronisktsmärtandepatellarsena,skhopparknävisasattbådebehandling

med ultraljudsledda skleroserande injektioner med polidocanol samt ultraljudsledd artroskopi kan ge goda kliniska resultat. Den ultraljudsleddaartroskopin leder dock till mindre smärta, snabbare återgång till smärtfriidrottsaktivitetsamtnöjdarepatienter.

En intressant iakttagelse är att båda metoderna var associerade med en förbättringavsenstrukturenochminskatblodflödeövertid.Detvaremellertidbaradenkirurgiskametoden somgav enultraljudsverifieradnormalisering avsenans tjocklek. Det tycks också finnas en korrelationmellan lågt blodflöde idetpatologiska (sjukliga)områdetochhögpatientnöjdhet samt lågsmärtavidaktivitet.Dennaiakttagelseärmycketintressantmenbehöverundersökasvidareistörrestudier.Resultatet av studierna i föreliggande avhandling visar att ultraljudsledd

artroskopisk shaving kan rekommenderas vid behandling av patienter med kronisktsmärtandehopparknäförattuppnåtidigsmärtfrihetochsnabbåtergångtillidrottsaktivitet.Avseendekronisksmärtandemittportionstendinosihälsenanvisas att ultraljudsledda skleroserande injektioner med polidocanol enligt ursprungsmetodengergodeffektpåsmärtan.

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INTR

OD

UC

TIO

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The normal tendon Tendons connect muscles and bones. They transmit the force created in themuscletothebonewhichenablesjointmovement.Healthytendonsareglisteningandivorywhiteincolourandfibroelasticintextureandtheyshowgreatresistancetomechanicalloads(Kannus2000).InthenormalpainlesstendontherearenovisiblebloodflowvisualizedwithUS/CD(Öhbergetal.2001).Tendonsarenotverytoleranttoshearingorcompressiveforces(Hessetal.1989),buttheyhaveagreatcapacitytowithstandtensileandstretchingforces.Atendonwithanareaof1 cm2iscapableofresistingaweightof500–1,000kg(Józsaetal.1997).Eccentricmuscle contractions - such as landing a jump produces the highest stress in the tendon(O’Brien1992;Kirkendalletal.1997;Ishikawaetal.2005).Toexemplify;involleyball,thepatellartendonisexposedtohighforcesandupto8kNhavebeencalculatedwhenlandingajump.Walkingonflatgroundgenerates0.5-2.6kNload(Komi1992).

Structure of the tendonTheextracellular tendonmatrix iscomposedofcollagenfibers,elastin,groundsubstance and anorganic components (Kannus 2000). Collagen,mainly type Iandelastinareembeddedintheproteoglycan-watergroundsubstance.Collagenaccountsfor65-80%ofthedryweightandelastinforabout1-2%.Thetendongroundsubstanceconsistsof60-80%water,proteoglycans,glucose-aminoglycans(GAGs) and structural glyco-proteins (e.g. Kannus 2000). Tenoblasts andtenocytes,areelongatedfibroblastsandfibrocytesthatliebetweenthecollagenfibers in a complexmanner (Hess et al. 1989). About 90-95% of the cellularelements consist of tenoblasts and tenocytes which produce collagen (Kannus2000).There are two steps in the synthesis of collagenfibrils, an intracellularandanextracellularstep.Primarilyprocollagen is formedand in thenextstepthe procollagen is converted to tropocollagen. Five tropocollagen molecules(microfibrils)arecross-linkedtocreatetheinsolublecollagenmolecule,collagenfibrils(O´Brienetal.1997).Multiplecollagenfibrilsthenprogressivelyaggregatetoformdefinablegroups–collagenfibers,whichisthebasicandsmallestvisible(lightmicroscopy) unit of the tendon (Hess et al. 1989;Kannus 2000). Thereisgreatvariationintermsofcollagencontentandtypeofcollagendistributionfrom“tendon-to-tendon”(Fanetal.1997).Itiswelldocumentedthatthecollagenfibrilsareorientednotonlylongitudinally,butalsotransverselyandhorizontallyandthelongitudinalfibrilsalsocrosseachotherformingspiralsandplaits.Thecomplex collagen structure with its crosslinks provides the tendon with tensile strength and enables the tendon to withstand high loads, while the groundsubstanceprovides structural support for the collagenfibers and regulates theextracellularassemblyofprocollagen intomature collagen (Åström1997).The

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complexstructureofcollagenandtheelastinmaycontributetotherecoveryaftertendonstretch(Butleretal.1978).

Thetendonisorganizedinprimary,secondaryandtertiarybundles(Kannus2000).Thenomenclaturemightvaryintheliterature.Thebasicunitsofatendonarethefibrils,andthesmallestcollagenousstructuresarethecollagenfibers(Hessetal.1989;Józsaetal.1997).Seefigure1.Thelengthofthecollagenfibersvariesbuttheycanbeas longasthetendon.Afineandlooseconnectivetissuesheetsurrounds the tendon; the epitenon,which contains blood vessels, lymphaticsand nerves. The epitenon is surrounded by the paratenon. The paratenon iscomposedoflooserandomlyorganizedcollagenfibrils,essentiallytypeIandtypeIII.Thesepermitfreemovementofthetendonagainstthesurroundingtissues,i.eworkingasanelasticsleeve(Hessetal.1989;Józsaetal.1997;Kirkendalletal.1997).Theendotenonisthesheetthatsurroundsthecollagenfibrilsinprimaryfibrebundles.Bloodvesselsandnervesruninsidetheendotenon.Thevascularsysteminsidethetendonconsistsoflongitudinallyorientedvesselslocalizedintheendotenon togetherwithveinsand lymphatics (Schatzkeretal. 1969).Thelongitudinaldirectionoftheintratendinousvesselsinthenormaltendonwillbefurtherdiscussed.

MetabolismHistoricallytendontissuewasthoughttobemetabolicallyinert,buttendoncells(tenoblasts and tenocytes) have been demonstrated to be more metabolicallyactivethanpreviouslybelieved.Thesyntheticactivitylessenswithincreasingagethough(Józsaetal.1997).Thetendonhasabalancebetweencollagensynthesisand degradation when healthy (O’Brien 1997). There are clear circulatoryresponsesandcollagen turnoverchanges related toactivity (Vailasetal. 1978;Langbergetal. 1998,2001,2007). Itappears that it takes48-72hours for thecollagentypeIformationtopeakafterexercise(Milleretal.2005).Thetendonhasaslowmetabolicrateandtheoxygenconsumptionis7.5timeslowerthaninskeletalmuscle(Józsaetal.1997;O’Brien1997).Ofclinical importance is that

Figure 1The hierarchial organisation of the tendon structure.(Józsa et al. 1997)


the tendon isallowed tocarry loadsandmaintain tension fora long time,butithasarelativelyslowhealingresponseandadaptationtochange.Thehealingafterarupturecantakeyears(Sharmaetal.2006)duetothelowmetabolicrate.Itislikelytobelievethatthesefactsareofimportancefortreatingpatientswithchronicpainfultendons.

General innervationTendons have been described to have innervation deriving partly from theparatenon. Paratenon nerves form rich plexuses that send a few branchespenetrating the epitenon, branches that inside the tendon anastomose withbranches originating from neighboring muscles and is described to cross themyotendinousjunction(Józsaetal.1997).Thenumberofnervesinsidethetendonisrelativelyfew.Theyfollowthebloodvesselsthatrunalongtheaxisofthetendonand anastomose via obliquely and transversally oriented nerve endings.Mostofthenervefibersaresensorynerveendingsonthesurfaceofthetendon.Themechanoreceptors seem to be concentrated to the myotendinous junction and tendoninsertions(Józsaetal.1997).Fourcategoriesofnerveendingsaremainlyseenintendons,ligamentsandjointcapsules.ThesearetypelRuffinicorpuscles(pressure receptors); type ll Vater-Pacini corpuscles (activated bymovement);type lll Golgi tendon organs (mechanoreceptors); and type lV receptors (freenerveendingsfunctioningaspainreceptors)(Józsaetal.1993).Concerningsensoryinnervationofthetendon,ithasbeenconcludedthatlarge

tendonsarerelativelyhyponeural.Inrecentyearstherehasbeenabigfocusinresearch in termsof the innervationof tendontissue.TheAchilles tendonandpatellartendonseemtohavesimilarpatternsofinnervation.Thesefindingsareofutmost importance when addressing the pathology and pain when treating patients withchronicpainfultendinopathywhichisthefocusofthisthesis.Informationand knowledge about the sensory and autonomous innervation has increased (Danielsson 2007; Bjur et al. 2005; Andersson et al. 2007). The innervationfoundinthetendonismainlyseeninnarrowzonesoflooseconnectivetissueandbloodvessels,zonesinterspersedbetweenthecollagenbundles(Danielssonetal.2006a).Ofthesethinnervefasciclesandperivascularnervefibersonlyveryfewdisplaypositivereactionsforthesensorynervemarkers.Mostofthenervesarelocated in the loose paratendinous connective tissue that surrounds the tendon (e.g.Danielssonetal.2006a).Inthistissue,largenervefascicles,aswellasthewallsofsomeofthelargerarteriesandafewofthesmallerbloodvessels,displaydistinct immunohistochemical reactions for the general nerve marker proteingeneproduct 9.5 (PGP9.5) (Danielson et al. 2006a).Parts of thenervefibersofthefasciclesandperivascularinnervationhavebeenshowntocorrespondtosensoryafferents,thesensorynervemarkerssubstanceP(SP)andcalcitoningene-

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relatedpeptide(CGRP)(e.g.Danielsonetal.2006a).Italsocontainsmarkersoftheautonomousnervoussystem,bothparasympathetic(vesicularacetylcholinetransporter) (Danielson et al. 2006b) and sympathetic neuropeptide Y (NPY)and tyrosine hydroxylase (TH) (Danielson 2007). These findings suggest theoccurrenceofbothasensoryandanautonomousinnervation.Thisobservation,puttogetherwithfindingsofautonomousnervemarkers(Danielsonetal.2006a,2008)seemstoindicatethattheinnervationofthedeeppartsofthetendonismainlyautonomousandnotsensoryinitstype.The general, sensory, sympathetic and parasympathetic (Danielson et al.

2006b,2007)innervationsinthechronicpainfultendinotictendondonotdifferparticularly from the corresponding innervations of the normal tendon. SP-positive nerve fibers, seen as free nerve endings, have been observed betweenthe collagen fibers in tendons of athletes with or without pain symptomsindicatingpatellartendinopathy(Lianetal.2006).Alocalproductionofsignalsubstanceswithin the tenocytes themselveshasbeenshown, signal substancesthataretraditionallyfoundintheneuronalsystem.Thisphenomenonseemstobeparticularlypronouncedintendinotictendons(Danielsonetal.2006a,2008).Evidenceofanoccurrenceofbothanacetylcholineproductionandmuscarinicreceptors(Danielsonetal.2006b),aswellasofacatecholamineproductionandadrenergicreceptors(Danielson2007),havebeenshownforthetendontissueinnormaltendonsbutinparticularwithintendinotictendons.Neurokinin-1(NK-1)receptor (theprimarySP receptor) immunoreactionhasbeendemonstrated inthewallsofbloodvesselsandnervefascicles/nervefibers(Forsgrenetal.2005).

The Achilles tendon – gross anatomyTheAchillestendonisthestrongestandlongesttendoninthehumanbody(Komietal.1992).Thegastrocnemiusandthesoleusmuscles(tricepssuraemuscles)mergetoformtheAchillestendon.Thetendonofgastrocnemiusis11–26cmlongandthelengthofthesoleustendonportionis3–11cm(Curvinetal.1984).Thecrosssectionalarea(CSA)ofthetendonis0.8–1.4cm2(Koivunen-Niemalaetal.1995)anditmayvaryaccordingtoactivity(Magnussonetal.2003).Themostproximalpartisratherflatbutduringitsdescenttowardsitsinsertionintothecalcaneus,itbecomesnarrowerandmorecircularuntilitinsertsintheformofadeltaintothecalcaneus(Reynoldsetal.1991).Theplantaristendon,ifpresent,normally runs between the triceps surae muscles and does not normally merge with theAchilles tendon (Josza et al. 1997;Doherty et al. 2006).TheAchillestendonmay rotate up to 90 degrees laterally during the descent. Thismeansthatfibersoriginallyposteriorbecomelateral,thelateralfibersbecomeanteriorandsoon.Thedegreeofrotationhasbeenfoundtocorrelatewiththedescribedvariationinfibersfromgastrocnemiusandsoleusrespectivelyandatwhatlevel


the fibers from soleus fuses with the fibers from gastrocnemius (Józsa et al.1997).Thisfacilitateselongationandelasticrecoilwithinthetendonandstoredenergy can be released during locomotion (McNeill 2002).Another importantfactoroftherotationisthatconcentratedstressmightoccurwhenthefibersfromsoleusandgastrocnemiusmerge.Thisismostprominentat2–5cmproximaltothecalcaneusinsertion,andcorrespondswellwiththeregionofthetendonthataccordingtosomeauthorshasthepoorestvascularsupply(Reynoldsetal.1991).IntheliteraturetheventralaspectsoftheAchillestendonisunclearbutdorsally,laterallyandmediallythereisaparatenon(looseconnectivetissue)(Kvistetal.1987;Franklyn-Milleretal.2009).InthisthesistheventralaspectoftheAchillestendonisofutmost interest.Weknowthatthedorsalboundaryof“Kager’sfatpad” (Kager’s triangle) is theAchilles tendon (Ly et al. 2004).Kager’s fat padconsistsprimarilyofadiposecells,butalsosomeelasticfibersandtypeIcollagen(Shawetal.2007).Kager’sfatpadissaidtoprotectandstabilizethebloodvesselsenteringthetendon(Theobaldetal.2006).Instudiesonrats,theKager’sfatpadhasbeenshowntobesuppliedbysensorynervefibers(Ackermannetal.2003,Shawetal2007).Whetherthereisa“paratenonlikestructure”ornotventraltotheAchillestendonstillneedstobeclarified.

The Achilles tendon – blood supplyBy some authors, themain blood supply of theAchilles tendon is considered,to be the paratendinous network of blood vessels, which originates from theanterior andposterior tibial arteries, aswell as theperoneal arteries.But it isalsoconsideredtocomemainlyfromthemusclesandisusuallydividedintothefollowingthreeregions,themusculotendinousjunction,thelengthofthetendon,andthetendonbonejunction.Themainbloodsupplyofthemidportionofthetendontakesplacethroughtheparatenon(O'Brien1997;Chenetal.2009).Mostoftheparatendinousvesselscanbefoundontheventralsideofthetendon,andlessareseenonthedorsalsideofthetendon(Zantopetal.2003).

The Achilles tendon – innervationThenervesupplytotheAchillestendonoriginatesmainlyfromthesuralnerve,vianervefasciclesthatoccursubcutaneously.Theinnervationisquitesparseinsidethetendontissue,withjustafewsmallnervefibersfollowingtheendotenonsepta(Józsaetal.1997).ThemainpartoftheinnervationoftheAchillestendonisfoundin theparatenon (Stilwell 1957;Andres et al. 1985).Formerly, the innervationwithintheAchillestendonhasbeensparselystudiedalthoughithasbeenofgreatinterestinrecentstudies.Theinnervationpatternhasbeensomewhatclarifiedbyfindingsofageneral(PGP9.5),asensory(SP/CGRP)andanautonomicnervoussystemintheAchillestendon(Bjuretal.2005;Anderssonetal.2007).

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The patellar tendon – gross anatomyThe patellar tendon is sometimes referred to as the ‘patellar ligament’ whendefinitionsareusedcorrectly.Butitissuggestedtorefertoitasatendonsinceits macroscopical and microscopical appearance more resembles tendon tissue and its function is directly controlled by the quadriceps muscle (Peers et al.2005).Thepatellar tendon is an extension of the quadriceps tendon inwhichthepatellaisembeddedasasesamoidbone(Mooreetal.1999).Seefigure2.Thequadricepsmuscleconsistingof,m.rectusfemoris,m.vastusmedialis,m.vastuslateralisandm.vastus intermedius, is thestrongestextensor intheknee joint.The vastusmuscleshave their origins at different sites of the femur, and theyinsertatthetibiaviathepatellaandthepatellartendon.Theyalsofunctionasflexorsofthehipjoint.Them.rectusfemoris,originatesinspinailiacaanteriorinferior and inserts into tuberositas tibiae. It has been shown that the tendonfibersofm.rectusfemorisgenerallyaretheonlytendonfibersofthequadricepsmusclethatactuallycontinueovertheanteriorsurfaceofthepatellatoformthepatellartendon(Reideretal.1981).Thepatellartendonisaflattendonandthenormalwidth isapproximately30mm(frontalplane) (Peersetal.2005),andthethickness4-5mm(sagittal/crosssectionalplane). Thepatellartendoncanbebroaderatitsattachmenttothetipofthepatellathanattheinsertiontothetibialtubercle(Andrikoulaetal.2006).Theaveragelengthofthepatellartendonisreportedtobe46mm(range35-55mm)(Reideretal.1981).

The patellar tendon – blood supplyThearterialbloodsupplyhasbeenthoroughlymappedinastudyof20specimensof humanpatellar tendons (Soldado et al. 2002). The arterial blood supply tothemedialpatellar tendonoriginates from thedescendingand inferiormedial

quadriceps muscle

quadriceps tendon

patella

patellar tendon

Figure 2 Figure 3


genicular arteries, branches of the femoral andpopliteal arteries, respectively.The lateral side is supplied by the lateral genicular arterioles from the mainanastomoticarches.Italsoobtainsbloodsupplydirectlyfromthemedialandlateralarteries(Soldadoetal.2002).Thelevelofbloodvesselsseenwithinthetendontissueislowandconsistsofbranchesofthepoplitealarteryandtherecurrenttibialanteriorartery;abranchofthetheanteriortibialartery.Forsimplicity;thepatellartendoncanbedividedintotwopartsconcerningthebloodsupply,thelowerandthe upper segment. The lower segment is supplied by superficial vessels fromthesupratuberculararchandtheuppersegmentreceivingdeepvesselsfromtheretropatellararch.Inthemiddlethirdofthetendontheseintratendinousvesselsanastomoseresultinginabipolarpatternoftendinousarterialsupply(Soldadoetal.2002;Andrikoulaetal.2006).Seefigure3.Incontrasttothetendon,whichis only supplied by blood in theway described above, the loose paratendinousconnective tissue (paratenon), receives arterioles from the main anastomoticarchesandalsoobtainsbloodsupplydirectlyfromthemedialandlateralarteries(Soldadoetal.2002).Thelevelofbloodvesselsseenwithinthetendontissueislowerthanthatseenintheparatendinoustissue(Soldadoetal.2002).

The patellar tendon – innervationThenervoussystemofthepatellartendonandsurroundinglooseconnectivetissueconsistsofsensoryandautonomicnervefibers(Ackermannetal.1999;Bjuretal.2005;Danielsonetal.2006a,b;Lianetal.2006).Theyderivefromneighbouringmuscular,cutaneous,peritendinousanddeepnerve trunks(Stillwell 1957).Thelooseparatendinousconnectivetissueofthepatellartendonisrichlyinnervated,but the tendon itselfhasa limited innervation.However,recently the tenocytesthemselveswere shown toproduce signal substances,normally associatedwithneurons(Danielson2007).Ofspecial interest in this thesis is theproximalanddorsalpartofthetendinotictendinopathicpatellartendon.Inastudyofpatientswith chronic patellar tendinosis, it was shown that there was an existence offreemyelinatednervefibersintheproximalosteotendinouszoneofthepatellartendon, and a periadventitial innervation of arteries, particularly in the IFP(Hoffa’s fatpad)adjacent to the inferiorpoleof thepatella (Sanchis-Alfonsoetal.2001).Furthermore,sympatheticfreenerveendingswerefoundtobepresentinthetendontissue,amajorityofthese,incontrasttothesensoryfibers,beingclearlyrelatedtobloodvessels(Lianetal.2006).

Autonomic innervation is mainly related to the blood vessels and both sympathetic and parasympathetic neuropeptides are implicated in the dynamic regulation of blood flow during exercise (Hannukainen et al. 2005). Thesympathetic NP mediate vasoconstriction (decreased blood flow) and theparasympatheticNPmediatevasodilatation(increasedbloodflow).

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TheHoffa’sfatpad–infrapatellarfatpadDorsaltothepatellartendontheinfrapatellarfatpad(IFP)islocated.AlsoknownasHoffa'sfatpad,namedbytheorthopedicprofessorAlbertHoffa,1859-1907.IFPisanintracapsular,extrasynovialstructurethatfillstheanteriorkneecompartment,andisrichlyvascularizedandinnervated.AlthoughtheprecisefunctionoftheIFPisunknown,studieshaveshownthatitmayplayaroleinthebiomechanicsofthekneeoractasastoreforreparativecellsafterinjury.Itsdegreeofinnervation,theproportionofsubstance-P-containingfibersandcloserelationshiptoitsposteriorsynovial lining implicatesIFPpathologiesasasourceof infrapatellarkneepain(Dragooetal.2012).Avarietyoftraumaticmechanismscanleadtohaemorrhageandinflammationincludingacute injury,repetitivemicrotraumaandiatrogenicinjury (Murakami et al. 1997; Ellen et al. 1999; Steadman et al. 2008). AcuteinjuryormicrotraumatotheIFPmayoccurfrombluntimpact,shearinjurywithcruciateligamenttearingpatellardislocation,torsionandimpingement.(Ogilvieetal.1994;Tangetal.2000;Kumaretal.2007;Abreuetal.2008,vonEngelhartet al. 2010). Examples of iatrogenic injury include fibrosis due to the creationof arthroscopy portals, scarring due to tendon harvest during anterior cruciateligamentreconstructionandfatpadresection(Rosenbergatal.1992;Paulosetal.1994;Murakamietal.1995;Bayaretal.2008).

Photos showing size and location of the Hoffa’s fat pad. At top left, patellar tendon released from its insertion at the tibial tuberosity. To the right, patellar tendon with Hoffa’s fat pad, view from the dorsal aspect. At bottom left, Hoffa’s fat pad resected from its insertion at the patella, view of the patellar tendon from the dorsal aspect.

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Epidemiology

Midportion Achilles tendinopathyAll patients in this thesis, paper I, were diagnosed as “midportion Achillestendinotictendinopathy”.Thistypeofpathologyisconsideredtobeinvolvedin55-65%ofallAchillestendoninjuries(Järvinenetal.1997,2005).Despitealloverusetheories,Achillestendinopathyhasrecentlybeenfoundin

peoplewithrelativelysedentary lifestyles.Somestudiesreportinguptoalmosta third of the patients not participating in any sports/physical activity on aregularbasis (Rolfetal. 1997;Alfredsonetal.2000).SomecommonactivitiesthatcanleadtoAchillestendinopathyincludemiddle-orlongdistancerunning,badminton,trackandfieldactivitiesetc(Fahlströmetal.2002).Itisconsideredthat 7-9% of professional athletes participating in sports consisting of a highfrequencyofrunningandjumpingpresentwithAchillestendinopathy(Lysholmet al. 1987; Almekinders et al. 1998; Cook et al. 2002; van Gent 2007). Forrecreationalrunnerstheconditionisfoundinup6-18%oftherunners(Alfredsonetal.2000;Schepsisetal.2002).Studieshaveshownthatupto30%sufferfrombilateralsymptoms(Paavolaetal.2002;Öhbergetal.2004).MidportionAchillestendinopathyismostcommonintheagegroupfrom30to60years(Paavolaetal.2000).Thedistributionofmalesandfemalesvariesinstudies.Arangebetween45%and89%ofmaleshasbeenreportedintheliterature(Paavolaetal.2000;Öhbergetal.2002;Alfredsonetal2005b).

Patellar tendinopathyInoneofthefewepidemiologicalstudiesoneliteathletesindifferentsports,theoverallprevalenceofpatellartendinopathywasreportedtobe14%.Theprevalencewaslowerinfemales5.6%,comparedto13.5%inmales(Lianetal.2005).Otherclinicalstudiesalsoshowthattheconditionismorecommoninmales(Myllymäkietal. 1990). However,nodifferencebetweenmalesand femaleswas found inaprospecticestudyon138physicaleducationstudents(Witvrouwetal.2001).Thehighestprevalence(40–50%)hasbeenreported inmalevolleyballplayers(Ferrettietal.1984;Gisslénetal.2005).Patellartendinopathyismostcommonlyseen in sportswithhighdemandson speed andpower from the leg extensors(Lianetal.2005).Othersportsthanvolleyball,wheretheconditionisseenareforinstancebasketball,soccer,footballandtrackandfield(Blazinaetal.1973).Thelong-termprognosisformaleathleteshasbeenshowntobepoorand53%oftheathletesabandonedtheirsportscareerduetopainsymptoms(Kettunenetal.2002).Patellartendinopathyisrarely,ifeverseen,inphysicallyinactivepeopleincontrasttomidportionAchillestendinopathy.

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AetiologyTheaetiologyandpathogenesisofchronicpainfultendinopathyisstillunclear.Theaetiologyisbelievedtobemultifactorial,involvingbothintrinsicandextrinsicriskfactors.Itshouldbestressedthatscientificevidenceoftheroleofintrinsicandextrinsicriskfactorsisstilllacking.Severaldifferenttheorieshavebeenpresented(Åström1997;Kannusetal.1997;Khanetal.1998b).Theknowledgeaboutthepain mechanisms is scarce and the condition in many ways still constitutes a pathologicalmystery(Cooketal.2004a;Hamiltonetal.2004;Alfredson2005b;Peersetal.2005;Danielsson2009).Chronicpainfultendinopathyisconsideredtobeadegenerativecondition,oratleastonewithafailedhealingresponsewithalackofatrueinflammatoryinfiltrateandresponse.Insummarytendonoverload/overuse is themost commonly accepted hypothesis concerning the etiology oftendinosis(Józsaetal.1997;Cooketal.2004a;Hamiltonetal.2004;Alfredson2005b;Peersetal.2005).

HistopathologyThehistopathologicalchangescanbecorrelatedtothoseofanincompletehealingofthetendon,whichverywellcorrespondstothewidelyacceptedtheorythatanincompletehealingcouldbethebasisfortendinosis.Thelackofinflammatorylesionsandgranulationtissuehasbecomeahallmark

in the tendinosis field (Denstad et al. 1979). It is, however considered thatinflammationmaybe an important first step in development of tendinosis. Inanimalstudiesontendonhealing,theinflammatoryinfiltratesappeartodisappearafter 18 days post tenotomy with suturing of the Achilles tendon (Enwemeka1989).Whenpatientsseekmedicalcareafteralongtimeofpainsymptoms,theyarenotlikelytobeinaprimaryinflammatoryphaseanymore,buttheconditionhasentereda“chronic”stage(Khanetal.1999).Tendinotictendonsshowadegenerationoftheextracellularmatrix(Riley2005)

withdisorderedarrangementofcollagenfibers,increasedvascularity(Khanetal.1999)andanincreaseoftendoncells,especiallycellswithroundednuclei(Åströmetal. 1995).Thevessels,whichareconsideredneovessels, areby someauthorsdescribedtoberandomlyoriented(e.g.Khanetal.1999),whileothershavenotedanincreasealsointhenumberofvesselsalignedparallelwiththetendonfibers(Maffullietal.2000).Thesecontradictoryfindingsconcerningbloodvesselsareofimportancewhendevelopingnewtreatmentmethods.Iwouldliketochallengethelaterfindinginthediscussionofthisthesis.Thecollagencomponentoftendinotictendons,alsodisplaychangescomparedtothenormaltendon.Thereisanincreasein collagen type III (Jarvinen et al. 1997;Riley 2005). Accumulation ofGAG:sandlipidsaswellascalcificationofthetendontissuehasalsobeendescribedintendinopathictendons(Riley2005).


Midportion Achilles tendinopathy – Clinical symptomsPatients commonly have a history of a gradual onset of tendon pain, oftenrelated toa change inactivity levelor recurrentepisodesofpain. Initially, thepatients often experience stiffness, pain or discomfort at the beginning of anactivity, followedby lesspainduringactivity,anda returnof thestiffnessandpainafterwards(Rogers1996).Whenbecomingchronic,pain increasesduringactivityandbecomesfunctionallyimpairing.Thepatientsoftencomplainaboutpostfunctionalandmorningstiffnessandsharpintolerableimpairingpainduringactivity,sometimesalsoatrest.ThischaracterizeschronicAchillestendinopathy.Itissuggested;themorepainduringactivityandstiffness,thepoorerstageofthetendoncondition(Cooketal.2002).Thelaterisalsodiscussablesincesometimesincreasedstiffnessisseenwhenthesharppainisdecreased.

MidportionAchillestendinopathy–ClinicalfindingsInspectionandpalpationwillrevealaswellinginthemidportionofthetendon.When palpating the thickening a remarkable sharp tenderness will be found.Theremaybesomepainduringpalpationevenifthereisnoinjury(Cooketal.2001b).Thetonusof thetendonwillbenormalandThompson’stestnegative.Rangeofmotionintheanklejointshouldalsobechecked.

Patellar tendinopathy – Clinical examinationTheclinicalsymptomsofpatellartendinosisischronictendonpain,onsetoforincreasedpainduringtendon-loadingactivityandimpairedfunction(Alfredsonet al. 2005b). Sometimes the patients also describe a feeling of instability ofthekneejointandmusclefatigueofthelowerextremity.Symptomsoftenstartgradually, and relate to changes in sports activity; duration and/or intensityand/orfrequency(Peersetal.2005).Mostoften,patientscomplainofpainafterstrenuousactivity,leadingtoimpairedperformanceandsometimesaugmentedby prolonged knee flexion, for example driving a car or going to the movies.Severecasespresentwithpainduringactivityofdailylivingand/oratrest(Cooketal.1998).Theareaofthepatellartendonmostfrequentlyaffectedbytendinosisis theproximalpart, involvingthe tendon-bone junctionat the inferiorpoleofthepatella,andthepainsymptomsaredescribedtobewelllocalizedtothisarea(Peersetal.2005)

Patellartendinopathy–ClinicalfindingsIntensetenderness,whenpalpatingtheproximalpatellartendonattheapexofpatella,isalwayspresentinpatientswithpatellartendinopathy.Palpationshouldbeperformedwiththekneefullyextendedandthequadricepsmusclesrelaxed.Whenthekneeisflexedto900,thetensioninthetendonincreasesandtenderness

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oftendecreases.Keepinmindthatatendonmaybetendereventhoughnoinjuryexists(Cooketal.2001b).Theonlyfindingwhenexaminingthetendonshouldbe the sharp pain, if crepitus or swelling is found, another diagnosis shouldbe suspected. Atrophy and hypotonia of the quadricepsmuscles is a commonclinicalsign.Asuddenandfastcontractionofthequadricepswiththekneejointin extensionwill oftenprovokepainwhich the patient often recognizes as thepainexperiencedduringatendonloadingactivity.Intrarticularfindingsshouldbeabsent.

Radiographs – x-ray and Magnetic Resonance Imaging – MRIHistorically,x-rayandMRIhavebeenusedasdiagnostictoolsascomplementsto thepatienthistoryandclinicalfindings inpatientswithanteriorkneepain.Duringrecentyears,imagingisusedinacutetrauma,andfortheassessmentofcasesofanteriorkneepainresistanttonon-operativemeasures.Theroleoftheradiographisnowlargelyrestrictedtocasesofsuspectedfracture.USisthemostrecommendedtechniqueforsuspectedtendonandbursalpathology(Soilaetal.1999;Ostlere2013).WhenusingMRIacommonfindingintendinopathiesisalocalwideningofthetendonandhighsignalintensityintheaffectedregionofthetendon(Johnsonetal.1996;Schmidetal.2002).Theseimagingfindingsmightsometimesbedifficulttodistinguishfrompartialrupturesinthetendon.Anotherdifficulty could be the variability of the normal/asymptomatic tendon inMRI,whichcouldbeapotentialsourceofdiagnosticinterpretation(Soilaetal.1999).

MRI images showing the same knee sagittal view. To the left normal findings, to the right tendinotic findings in the patellar tendon at the apex with oedema dorsally in the central part.


Ultrasound and colourDoppler – US/CDUShasbeenusedforclinicalmusculoskeletalexaminationsforalongtime(Fornage1986)butnot focusedon tendonpathology. In thepast,USwasconsideredacomplement toMRI for the imaging of tendons.ModernhighresolutionUS ishighly competitive, and it is today the preferred choice when imaging tendoninjuries(Rasmussen2000).Itisproventobeaccurate,cost-effective(Jacobson1999)andavalidmethod(Martinolietal.1993).Itisrecommendedtobethemostsuitablemethodwhen it comes to investigating superficially located structuressuch as tendons, for example Achilles and patellar tendons (Soila et al. 1999;Ostlere 2013).US is a dynamic examinationwhich is an important advantagecomparedtoMRI.TherearestudiescomparingtheaccuracyofMRIandUSwhenconfirmingclinicallydiagnosedpatellartendinopathy.US/CDandinterestinglyalsogreyscale(GS)ultrasoundprovedtobemoreaccuratethanMRI(Wardenetal.2007;Garricketal.2008).Intendinosis,GS/USrevealsathickeningofthetendon,irregularorganisation

ofcollagenfibersandalsohypoechoicareas(Khanetal.1996)InthemidportiontendinoticAchillestendinopathy,thehypoechoicareasare

seenontheventralsideofthetendonwherethetendinotictendonisthethickest.Inthetendinoticpatellartendinopathytheseareasareseeninthedorsalsideofthetendonneartheapexpatella.ColourDoppler is another advantage of ultrasound. CD shows visible blood

flow and this gives us a possibility to study the blood flowwithin the tendon(Weinbergetal.1998;Öhbergetal.2001).

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Treatment mehods of the chronic painful tendonThere is a large variety of different treatments. However, very few have beenadequatelyscientificallystudied.Thisfield isadvancingvery fast trying tofindnew treatmentmethods,whichmight explainwhy there is so sparse scientificevidence for many of the existing treatment methods used today. Eccentrictrainingisthemostevidencebasedtreatmenttoday(Bahretal.2006;Gaidaetal.2011;Nilsson-Helanderetal.2012).

RestRestandavoidanceofpainful activities areusually recommended.Hence, thiscan be adequate in an acute injury (Angermann et al. 1999). But it is not thecaseinchronicpainfultendinopathy.Itissaidthatsincewearedealingwithanoveruse“injury”(Józsaetal.1997)activitycouldworsenthecondition.However,patientswhohavetriedtoreststillseekhelpfortheirchronicpainfulcondition.Immobilization of the tendon may cause tissue athrophy (Peers et al. 2005).Restmayreducethesymptoms.While,recoveryisnottobeexpectedsincethesymptomsusuallyreoccur(Ferretti1986;Colosimoetal.1990).Therearesomerecommendations but no clear protocol in the literature about partially resting fromtendonloadingactivityandadjustingactivitywhenexperiencingpaininthetendon (Wilson et al. 2005;Rees et al. 2009).This hasnot been scientificallyinvestigatedinpatientswithchronicpainfulpatellartendinopathy,though.

Nonsteroidalanti-inflammatorydrugsandsteroidinjectionsConsideringthemodernresearchfindingsthata“traditionalinflammation”isnotpresentinthesetendons,itseemscontradictorytotreatthechronicpainfultendonaddressedinthisthesiswithanyNSAIDorinjection.Intheliterature,NSAIDshavebeen shown to reduce pain during medication but have not being able to heal this chronicpainfulcondition(Almekindersetal.1998,1999).Steroidinjectionsseemtogivepainreliefintheshortrunbutthenthesymptomsoftenreoccur(Almekindersetal.1998).Therearestudiessuggestingthatsteroidinjectionsmaypredisposeforspontaneoustendonruptures(Józsaetal.1997;Wilsonetal.2005).Theinjectionofsteroidsareheavilyquestionednowadays(Andresetal.2008).

Extracorporeal shockwave treatmentTheuseofextracorporealshockwavehasexplodedinpopularityduringtherecentyearsand isoftenusedasa complement toeccentric training.Mostoften, thediagnosisisobtainedsolelybyclinicalexamination.Thereissparseevidenceandnotreatmentprotocolhasbeensuggestedintheliterature.ItisconcludedthatfurtherstudiesareneededwhenusingESWTasatreatment inpatientswithachronicpainfultendon(Rompeetal.2008;Foldageretal.2012).


PhysiotherapyPainful eccentric muscle training has shown good long term results whentreatingthechronicpainfultendon.Eccentriccontractionsseemtobesuperiortoconcentricones(Mafietal.2001;Jonssonetal.2005).Moreover,itissuggestedthateccentrictrainingshouldbecarriedoutwithpain/somediscomfortandwithaheavyload(Stanishetal.1986).ForthemidportionAchillestendinopathythereare a lot of studies and importantly the results are reproducible (Alfredson etal. 1998,Fahlströmetal.2003;Rompeetal2007).When itcomes topatellartendinopathythestudiesarefewerandtheyoftenhavesmallsamplesizesandrelativelyshortfollow-uptimes(Cannelletal.2001;Jonssonetal.2005;Youngetal.2005;Bahretal.2006).Betterresultsareachievedifaddingadeclineboard(Purdametal.2004;Jonssonetal.2005;Youngetal.2005).Duringtheperiodofrehabilitationthepatientsshouldavoidsportingactivities(Purdametal.2004;Visnesetal.2005).

Sclerosing injectionsSclerosing therapy is widely used for treating varicose veins of the lowerextremities and oesophagus, haemorrhoids and teleangiectases of the skin.Polidocanol(aethoxysclerol)wasfirstdevelopedasalocalanaesthetic.Itisusedas a sclerosing agentwith very few side effects (Conrad et al. 1995;Winter etal. 2000;Öhberg et al. 2002). Polidocanol is used in different concentrations5, 10and30mg/ml.Theactivesubstance isanaliphaticnonionisednitrogen-freesurfaceanaesthetic.Polidocanolhasaselectiveeffectonthevascularintimacausing thrombosis of the vessel (Guex et al. 1993). It can act indirectly bycompressiveeffectsonvesselsbytissueexpansion.Itisusedbothforintravasalandperivascularinjection.Theperivasculareffectisanimportantpropertywhenverysmallvesselsarebeingtargeted.Itisplausiblethatthesclerosingeffectofpolidocanol on the vessels alsomight affectnerves adjacent to theneovessels,either directly (by destruction) or indirectly (by ischaemia). Polidocanol has asclerosingeffectandalocalanaestheticeffect.

The hypothesis behind the treatment is to target the areas in the tendon with increasedbloodflowassociatiedwithpain(Öhbergetal.2002;Alfredsonetal.2003b; Alfredson et al. 2005a; Cook et al. 2004b). Treatmentwith injectionsofthesclerosingsubstancepolidocanol5and10mg/mlhaveshownpromisingclinicalresultsandnosideeffects(Öhbergatal.2002;Alfredsonetal.2005a,c;Hoksrudetal.2006;Hoksrudetal.2011).

Other injection treatmentsThere are a variety ofmodels of injectionswith different theories about theirmechanisms. Most injections are given blindly; without US guidance. Both

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extratendinous and intratendinous injections are given. Injecting platelet richplasma (PRP) as well as ESWT has become very popular. However, a recentrandomized study showed no differences between saline injections and PRPinjections(deVosetal.2010).Othersubstancesinusearehyperosmolardextrose,autologousbloodandMMP-inhibitors(Maxwelletal.2007;Orchardetal.2008;deAlmeidaetal.2012;Pascual-GarridoCetal.2012;Wileyetal.2013).

Surgery in generalWhenreviewingtheliteratureitisstrikinghowdifficultitistocomparedifferentstudies,accordingtothemethodusedandclinicaloutcome,sinceitisdifficulttotellwhatconditionsofthepatientsthatreallyhavebeenincluded.Thediagnosticsandindicationsforsurgerydifferconsiderably.Ifnon-operativetreatmentfails,surgeryisoftenrecommended,althoughitis

the“lastattemptoftreatment”(Colosimoetal.1990;Maffullietal.1999;Pannietal.2000;Alfredsonetal.2007a).Asurgicalapproachisalsousuallyonlytobeconsideredafteratleast3-6monthsnon-operativetreatment(Angermannetal.1999;Khanetal.1998;Bahretal.2006).Therearenumerousdifferentsurgicalmethodsdescribed in the literature,whichmay reflect the lack of randomizedclinical trials comparing different procedures (Khan et al. 1998b; Peers et al.2005). Concerning surgical treatment of Achilles tendinopathy and patellartendinopathy critical reviews show that studies with a poor scientific designgenerallyhavereportedgoodclinicalresults,whereasstudieswithagooddesignhavereportedpoorclinicalresults(Colemanetal.2000;Tallonetal.2001;Bahretal.2006).Inconclusion,itseemsasiftheresultsaftersurgeryarevaryingandunpredictable.

Surgery in Achilles tendinopathyThe variety of surgical approaches to treat chronic Achilles tendinopathy hasbeen grouped into four different approaches. These are (1) open tenotomywith removal of abnormal tissue, paratenon not stripped; (2) open tenotomywith removal of abnormal tissue, paratenon stripped; (3) open tenotomywithlongitudinaltenotomy,withorwithoutparatenonstripping;and(4)percutaneouslongitudinaltenotomy(Tallonetal.2001).Surgicalresectioninvolvesexcisionofwhatismacroscopicallyfoundtobepathologicaltissueandisanintratendinousprocedure. The result of surgical treatment is reported to have a success ratearound70%orbetter (Schepsis et al. 1994;Morberget al. 1997).However, asdiscussed above this success rate may be doubtful since the diagnoses andindicationsvaryandsometimesincludepartialruptures.Recently,aminimallyinvasivesurgicalprocedurehasbeendescribed,basedon thesame ideaas thesclerosinginjections,wherethenewlyformedvesselsandaccompanyingnerves,


ventral to the Achilles tendon, are targeted and no tendon tissue is excised(Alfredsonetal.2007b).

Surgery in patellar tendinopathyMethods available are either open surgery or arthroscopic surgery. Surgicaltechniques involve forexample;osteotomy,resectionof thedistalpatellarpole(Pecinaetal.2010),openpatellartenotomytoremovemacroscopicallyabnormaltissue, arthroscopic patellar tenotomywith orwithout removing the tip of thepatella, and US-guided percutaneous longitudinal tenotomy (Coleman et al.2000a).Thereisalongrecoveryforthedifferentsurgicalmethodsusedtotreatchronicpainful patellar tendinopathy. In one retrospective study, “traditional”opensurgery,renderedamediantimetoreturntopreinjurylevelofactivityofabout10monthsandforarthroscopictenotomyaboutsixmonths.Thesuccessratewithbothtreatmentswasabout50%andtherewerenosignificantdifferencesbetweentheopenandthearthroscopicprocedure(Colemanetal.2000b).Inareviewof23studies,Colemanetal. (2000a)evaluatedthesuccessrate

of surgical outcome, showing varying results, 46–100% good results. Whencomparing the non-operative treatment eccentric training with “traditional”open tenotomy, no benefits were shown with surgery (Bahr et al 2006). In arecent systematic review comparing minimally invasive arthroscopically assisted procedures and open surgery in the treatment of chronic proximal patellartendinopathy(Mucciolietal.2013),theydidnotseeanystatisticallysignificantdifferences in the treatment results according pain. Nor were any differencesshownconcerningpainless(orwithminorpain)returntopreinjuryactivitylevel.Themethodologyofstudiesinthisfieldhasimprovedoverthepast15years,butwell-designed RCTs using validated patient-based outcome measures are still lacking(Mucciolietal.2013).

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GeneraldefinitionsThereisalackofconsistentterminologyrelatingtochronicpainfulconditionsintendonsandtheterminologycanbeconfusingwiththeconsequencesthatscientificstudies aredifficult to compare. In thepast different termshavebeenused inordertodescribethechronicpainfultendon.Theseare,forinstance,tendinitis,tendonitis, tendinosis, tendinopathy, peritendinitis, paratendinitis, insertionalandnon-insertionaltendinopathy,partialrupture,calcifiedtendinopathy,apicitisandchronicpainfultendon.

Tendinitis and tendonitishavebeenwidelyused,assumingthattherewasatrueinflammationwithinthetendon.Tendinitisisprimarilyinvolvingthetendonshowing an inflammatory response within the tendon and is often associatedwithreactiveparatendinitis(Józsaetal.1997).Researchinthisareahasevolvedduring the years, several observations, including histological and biochemicalstudies(Khanetal.1996)andintratendinousmicrodialysis(Alfredsonetal.1999;Alfredsonetal.2001),haveshownanabsenceofatrueprostaglandin-mediatedinflammatory process inside the chronic painful tendon (Kannus et al. 1991;Åströmetal.1995;Alfredsonetal.1999;Alfredsonetal.2003a).Thisiswhythistermwillnotbeusedinthepresentthesis.

Tendinosis has been proposed to describe the findings interpreted as beingdegenerativeinthischronicallypainfulstateofthetendon(Khanetal.1999;Peersetal.2005).ThetermtendinosiscanbeusedregardlessofpainorsymptomsanditreferstointratendinoushistopathologicalchangeswhichcanbevisualizedandobjectivelyverifiedbyUS,MRIorbiopsies(Maffullietal.1998;Alfredsonetal.2005b).

Tendinopathy is widely recommended to describe a condition with tendon pain,swellingandimpairedfunction,therebynotassuminganyinformationoftheunderlyingpathology(Khanetal.1998;Maffullietal.1998;Peersetal.2005;Riley2005).

Peritendinitis is characterized by a true inflammation in the paratenon (Åström1997).

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Midportion Achilles tendinopathyThemostcommontendinopathicconditionsintheAchillestendoncanbefoundatthreedifferentlocationsalongitslength,(1)insertional–atthecalcanealinsertion(Carmontetal.2007),(2)midportion–at2-6cmabovetheinsertion,and(3)myotendinous–atthemuscle-tendonjunction(Movin1998).InpaperIofthisthesis,allpatientsincludedhadachronicpainfulmidportiontendinoticAchillestendinopathy,locationnumber2accordingtoabove.Subjectively,allpatientshadtohaveexperienceddisturbingpainduringactivityforalongerperiodthanthreemonths,(toconsideritchronic)(Kettunenetal.2002).Noacuteonsetofpainwasallowed.Objectively,adistinctandsharptendernessinthemidportionoftheAchilles tendon,anoticeablemidportionswellingwasnecessary,butanormaltonusandanegativeThompson’stest.PathologicalGS/USfindingsintheventralpartofthethickenedmidportionAchillestendonwithhypoechoicareashadtobepresent.CDfindingsofincreasedbloodflowinatransversaldirectionwasalsomandatory.TheseUS/CDfindingshadtostrictlycorrespondtothetenderandpainfulareaofthetendon.IfanyoftheabovementionedsignsweremissingwechoosenottocallitmidportionAchillestendinopathy,andthosepatientswerenotconsideredforinclusioninanystudyofthepresentthesis.Tofollowallthedefinitionsintheliteraturewecoulddescribeourincludedpatientstosufferfrom“chronicpainfulimpairingtendinoticmidportionAchillestendinopathy”.

Patellar tendinopathy/jumpers kneeIntheliteraturetherearemanydefinitionsofpatellartendinopathyandjumper’sknee.Sincethenomenclatureandsuggestedtreatmentsoftenvariesconsiderablyitisdifficulttomakecomparisonsbetweendifferentstudies.Jumper’s knee isusually a clinically verified conditionwith exercise related

painandtendernesstopalpationinthepatellartendonattheinferiorpoleofthepatella (Blazinaetal. 1973;Khanetal. 1998;Maffullietal. 1998).Theclinicaldiagnosisofjumper’skneedoesnotrequireverificationbyimagingfindings.For inclusion inallstudiesof this thesis thedefinitionof jumper’skneehas

been narrowed. A very strict definition of tendinopathy has been used whenincludingthepatientsinordertomakesurethatthesamesortofconditionwastreatedinallpathologicalpatellartendons.Subjectively,allpatientshadtoexperiencedisturbingpainduringactivity,and

they had to have experienced the sharp typical pain during a longer period than threemonths,toconsideritchronic(Kettunenetal.2002).Noacuteonsetofpainwas allowed nor any subjective intra articular symptoms. Objectively, distincttendernessattheapexofthepatellawasnecessary,butnoswellingorothersignsofintraarticularpathologywhenexaminingthekneewasallowed.Pathologicalgreyscale US findings in the proximal, dorsal part of the tendon with tendon


thickeningandhypoechoicareashadtobepresent,CDfindingsofincreasedbloodflowinatransversaldirectionwasalsomandatory.TheseUS/CDfindingshadtostrictly correspond to the tender andpainful area of the tendon. If any of theabovementionedsignsweremissingwedidnotdefinetheconditionasjumper’sknee,andthosepatientswerenotincludedinanyofthestudiespresentedinthisthesis.Tofollowallthedefinitionsintheliteraturewecoulddescribeourincludedpatients to suffer from“chronicpainful impairing tendinoticproximalpatellartendinopathy”. In summary, in the present thesis, jumper’s knee, consists ofmultiplefindingsbothsubjectiveandobjectiveandwillbereferredtoasPT/JK.

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Aims and hypothesis

I. Theaimofthisdouble-blindrandomizedcontrolledtrialwastoevaluate whethertherewereanydifferencesintheclinicaleffectsbetweeninjections of polidocanol in the two different concentrations, 5 and 10mg/ml, in patientswithchronicpainfulmidportionAchillestendinopathy/tendinosis. The hypothesis was that the use of higher concentration (polidocanol 10mg/ml)wouldleadtoalessnumberoftreatmentsandlowervolumes neededforgoodclinicalresults.

II. The aimwas to visualize the areawith increased blood flow in patients with jumper’s knee/proximal patellar tendinopathy during arthroscopic surgery. Therefore, we wanted to evaluate the possibility of performing knee arthroscopy with simultaneous ultrasound and colourDoppler guidanceandpresentitinatechnicalnote.

III. The aimof thispilot studywas to evaluate the effects of amore radical destructionoftheareawithneovesselsandnervesonthedorsalsideofthe tendonbyusingUSguidedarthroscopicshaving.

IV. Theaimofthisrandomizedstudywastocomparetheclinicalresultsafter treatment with ultrasound and colour Doppler-guided sclerosing polidocanolinjectionsandUS-guidedarthroscopicshavingtotrytoclarify whether either treatment, both performed outside the tendon, is significantlysuperiortotheother.Theprimaryoutcomemeasurewasto evaluatetheclinicaleffectofthetreatmentbyhavingthepatientstoscore thelevelofpatellartendonpainduringtheirspecificsportorrecreational activity,andatrest,andevaluatepatientsatisfactionwiththeresultsofthe treatment.

V. The aim of this study was to compare the US/CD findings, pain and clinical outcome, before and after treatment between US/CD guided sclerosing injections and US/CD-guided arthroscopic shaving, in a longertermfollow-up.Ourhypothesiswasthatatendinotictendontreated with US/CD-guided arthroscopic surgery, including shaving outside the dorsal side of the tendon,would sonographically show signs of a better recovery than a tendon treated with US/CD-guided sclerosing polidocanolinjections.

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SubjectsAllpatientsinthisthesiswerereferredtotheCapioArtroClinicAB,Stockholm,Swedenforpossibletreatmentoftheirchronicpainfultendinopathy,i.epainformorethanthreemonthsandnoacuteonset.

Study IForty-seven patients (52 tendons) were consecutively referred to the CapioArtroClinicwithchronicpainfulmidportionAchilles tendinopathy.Theywererandomizedtotreatmentwithpolidocanol5mg/mlor10mg/ml.Themajorityofthepatientswererecreationalathletesbuthadarathersedentarylifestyle.BMIwasintheupperlevelofnormal(>25).Formoreinformationaboutthepatients,pleaseseesummaryofpapers(Table1).

Studies III-V,Allpatientswereactive,rangingfromrecreationaltocompetitionlevelandtheyall had painful proximal patellar tendinopathy. They were younger than thepatientssufferingfromAchillestendinopathyandtheyweredominantlymales.Theywere all examinedwithUS/CD to confirm the tendon changesdescribedaboveindefinitionsforthisthesis.Theyallhadalongdurationoftendonpainduringactivity.Formoreinformation,pleaseseesummaryofpapers.

Study IIIFifteeneliteandrecreationalathleteswithalongdurationofpainsymptomsfrom15patellartendonswereincluded.AllpatientswerereferredtotheCapioArtroClinicinStockholm,Sweden,ortheSportsMedicineUnitinUmea,Sweden,forevaluation(Table2).

Study IVForty-fivepatients(52tendons)wereincluded.AllpatientswerereferredtotheCapio Artro Clinic in Stockholm, Sweden, with the diagnosis chronic painfulpatellar tendinopathyanda longdurationofpain.Sevenpatientshadbilateraltendonchanges(Table3).

Study VPatientsincludedinthisstudywerethe45formerparticipantsinstudyIVandanadditional9patients fromthepilotstudy–studyIII.Atotalof43patients (41males/2females)with57treatedtendonschosetoparticipate.Formorebasicdataseetable2,table3andtable5.

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General inclusion and exclusion criteriaAll patients referred to the Capio Artro Clinic AB, Stockholm, Sweden withchronicpainful tendinopathy ineithermidportionAchilles tendonorproximalpatellartendonwereconsideredforinclusion.

Study I, inclusion criteria, midportion Achilles tendinopathy • ChronicpainduringactivityintheAchillestendonformorethanthree months,noacuteonsetofpain• Clinically noticable swelling and tenderness when palpating midportion Achilles tendon• Thompson’stestnegativeandnormaltonus• US/CDfindingsinformofhypoechoicareasintheventralpartofthetendon andhypervascularityenteringthetendonfromtheventralside corresponding to the tender area

Study III-V, inclusion criteria, patellar tendinopathy• Painduringactivityattheapexpatelladuringactivityformorethanthree months,noacuteonset• Clinicallytendernessatthemostproximalpartofthepatellartendon, withthekneeinfullextensionandquadricepsrelaxed,andnootherfindings suggesting intra articular pathology• US/CDfindingsinformofhypoechoicareasinthedorsalpartofthetendon andhypervascularityenteringthetendonfromthedorsalsidecorresponding tothetenderareaintheproximalpartofthetendon

Exclusion criteria• Previous surgery or injection treatment• Chronicinflammatorydisease• Medicationwithwarfarine,anantithromboticmedicament• Allergy to localanestetic• Neurologicaldisorderscausingpainintheaffectedlimb

Diagnostics in this thesis

Patient historyAllpatientswereinterviewedandthefollowingparameterswererecorded;• Durationofpainduringactivity(>3months)• Onsetofsymptoms,acuteorgradual?• Thecharacterofpain;sharpandintolerable?Impairing?• Medication


• Earlier treatments• Height and weight• Allergies or systemic diseases or medical issues• Previous injuries

ClinicalfindingsAchilles tendon – examined in a prone position with gastrocnemius relaxedand feet hanging outside the bench. Swelling (0-3), tenderness (0-3), locationofswellingandtenderness;midportionordistaltendon,tonus,rangeofmotion(ROM)andThompson’ssignwasnoted.Patellartendonandkneejoint–examinedinasupinepositionwithquadriceps

relaxed and the knee extended.We always startedwith an inspection in ordertonotemuscular tonusand to see if there isanyatrophyorany intraarticularswelling.Thenwecontinuedwithastandardexaminationtoruleoutothersignsofintraarticularpathology.Concerningthetendonwepalpatedthepatellartendonandnoteifthereisanytenderness(0-3)intheproximalpartattheapexpatellae.

Ultrasound and colourDopplerInallstudiesinthisthesisthediagnosisatbaselinewasconfirmedwithUS/CD.All tendonswereexaminedwithhigh resolutionGS/US/CDusingaWSX13-5linearmultifrequencyprobe(Siemens-AcusonAntaresSonoline),atagreyscalefrequencyof11.4MHzandaCDfrequencyof8.9MHz.Thesameequipmentwasusedforallexaminations,andthesameexperiencedsonographerperformedallUS/CDevaluationsatbaseline,atshorttermfollow-upsandatendpoint.Intra-observerreliabilityforevaluationofthetendonstructureandneovascularization(localizedhighbloodflow)hadbeentested,aswellasreproducibilityformeasuresofthickness(forvaluesplease,seeStudyV).

Treatment methods in this thesis

Sclerosing injectionsBefore the injection treatment, the skin was disinfected with a solution ofchlorhexidine. The skin was draped with a sterile paper-cover exposing onlytheareaforinjection.Theinjectionwasperformedwithaø0.7x50mmneedleconnectedtoa2mlsyringe.Thedecisiontotreatwasmadebytheorthopedicspecialist and the same experienced ultrasonographer performed all US/CDexaminations. The injection was performed dynamically, with the aid of real-time GS/US/CD technique. Two different concentrations of polidocanol wereused for treatment, 5mg/mland 10mg/ml.Very small volumes0.1–0.2ml amaximumof2ml/treatmentsessionofpolidocanolwasinjectedintotheareas

43

oflocalincreasedbloodflow.Needletipwasaimedattheentranceofthevesselsintothetendon.PolidocanolwasinjecteduntilthevesselswerenolongervisibleatallwithUS/CD.Thevesselsapproachedhadtocorrespondwiththepalpablepre-injectiontenderness.Apressurebandagewasthenappliedfor24hoursandthepatientswereinformedabouttheregimenaftertheinjectiontreatment.Thepatientswereallowedcarefulwalkingrightafterthetreatmentandfull tendonloading-activitywas allowed 14days after the treatment.Amaximumof threetreatmentswithatleast6–8weeksinbetweenweregivenbeforeevaluation.US/CDimagesweretakenbeforeandaftertheprocedure.

Injecting midportion tendinotic Achilles tendinopathyAllpatientslayinaproneposition,theUSprobewasheldonthedorsalsideoftheAchillestendon,parallelwiththefibers,longitudinalplane.Theinjectionwasalwaysdonefromthemedialsideofthetendontominimizetheriskofcontactwith the suralnerve. Injectionsweremadeonlywhere the vessels entered theventralpartofthetendonandonlythevesselsthatraninatransversedirectionwereapproached.ImagesshowingUS/CDfindingsbeforeandafterinjections.

Injecting tendinotic patellar-tendinopathy/jumper`s kneeAll patients lay in supine position with their knee joint in extension,quadriceps totally relaxed. The USprobewasheldontheventralsideofthepatellartendon,parallelwiththefibersin a longitudinal plane. To confirmthe position of the needle the probewas sometimes also held transverse to the fibers. Injections were made onlywhere the vessels entered the dorsal partofthetendonandonlythevesselsthat ran in a transverse direction were approached.


US-guided arthroscopy – patellar tendinopathyArthroscopywasperformedinlocalanaesthesia.Localanaesthesialidocainwasinfiltrated into the anteromedial, anterolateral portals and also injected thejoint. The patients were in supine positionwith straight knee and quadricepsrelaxed.Thestandardanteromedialandanterolateralportalswereused.Wehadapressure-controlledpump.US/CDwasusedper-operatively.

Sterile US gel was used and the US probe wasdraped.Whensurgery isperformedin general anaesthesia, or when usinglocal anaesthesiawithout adrenalin, theincreasedbloodflow(neovessels)canbeseen per-operatively using CD-technique (ifthejointpressureiskeptlow).GS/USclearly visualizes the tendon structure pre-andper-operatively.First, a standard arthroscopical

evaluation of the whole knee joint wasperformed. Then the patellar tendoninsertion into thepatellawas identified.For shaving, we used a 4.5 mm fullradius blade. Simultaneous US guidedthe procedure. It is important thatthe shaverblade and the tube of thearthroscope is inserted into the joint as perpendicular as possible to the proximal partof the tendon,allowing forabetterultrasoundview.Careful shaving was performed in

order to diminish the increased blood flow (neo-vessels) corresponding to thetendinotic area on the dorsal side ofthe tendon. We used the US monitor,preferably with the transducer showingthe cross sectional view of the tendon.We carefully avoided from resectingtendon tissue and we only loosened the Hoffa’s fat pad (IFP) from the centralpart of its attachment to the patella.We tried to avoid resection of the IFP

45

asmuchaspossible.Theprecisionoftheprocedurewasincreasedcomparedtowhenonlyusingthearthroscopymonitor.Thewholeprocedureofshavingwasclearly visualized and we had the impression that there was less tissue trauma this way with simultaneous US/CD-guidance. The portals were closed with atape.Abandagewasusedfor24h.US/CDimagesweretakenbeforeandaftertheprocedure.Sinceevaluatingandcomparingnewtreatmentmethods,nospecificrehabilitationprotocolwasgiven.

US/CD findings directly after surgery with no pressure in the joint, no remaining high blood flow in the tendinotic area of the tendon.

GS/US images showing US findings when finishing the procedure, still pressure and fluid in the joint. Hoffa’s fat pad separated in its central attachment from the patellar tendon.

GS/US showing the tip of the shaver during arthroscopy, longitudinal plane and cross sectional plane.

US/CD findings before surgery in a tendinotic patellar tendon with increased blood flow.


Outcome measures

Visual analogue scale for pain rating Thevisualanaloguescale(VAS)wasusedandthepatientsratedtheamountofpaininthetendon.VASisa100mmlongscale,wherethepatientsestimatetheirpain.0-equals“painless”and100equals“worstimaginablepain”.Theyestimatedbothpainduringtheirownchosentendonloadingactivityandpainatrest.Thisestimationwascarriedoutatbaselineandatallfollow-ups.AllVASratingswererecordedbythesameandindependentpersonandsavedinadatabase.VASisavalid,reliableandprecisescale(Williamsonetal.2005).Thetest-retestreliabilityis very high (intraclass correlation coefficient 0,97) for acute pain (Bijur et al.2001).A30-35%reductioninpainintensitywasconsideredtorepresentclinicalrelevance(Rowbothham2001).

Satisfaction with treatmentOn a similar scale as VAS, 0-100mm long the patients recorded if theywere“satisfied”or“notsatisfied”with their treatmentatevery follow-up.“Satisfied”meantpainlessreturntotheir,atbaseline,chosentendonloadingactivityequaled100,and“notsatisfiedatall”equaled0onthescale.If“notsatisfied”therewasno return to previous tendon loading activity or still pain in the tendon during tendonloadingactivityindifferentdegrees.

US/CDfindingsInallstudiesinthisthesisthediagnosisatbaselinewasconfirmedwithgreyscaleUSandCD.InstudyV,theUS/CDfindingswereoneoftheprimaryoutcomes.TheUSinvestigationswereperformedaccordingtoaroutineprotocol.Tendonthickness(anteroposteriordistance)wasmeasured in the longitudinalplaneatthemostproximalpartofthetendoninthecentreofthemosttendinoticregion,representingthewidest/thickestpart.Tendonstructureandneovascularisation(localizedhighbloodflow)wereevaluatedwiththesamecriteriathatwereusedatbaselineandatshorttermfollow-ups,accordingtoamodifiedÖhbergmodel(Öhbergetal.2002;Abateetal.2012).

Ethical considerationsAllstudiesinthepresentthesiswereconductedwiththeapprovaloftheEthicalCommittee at the Medical Faculty of the Karolinska Institutet, Stockholm,Sweden, No 2005/1246-31/2 (study I-IV) and No 2011-929-32 (study V). Allpatientswereinformedbothverballyandinwritingpriortoconsent.

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Statistics

Power analysisA power analysis was based on the results from two previous pilot studies(Alfredson et al. 2005; Hoksrud et al. 2006). The analysis showed that 20individualsineachgroupwereneededtogiveapowerof80%tofindadifferenceof50mminVASbetweenthegroups,ona5%significancelevel.Weestimatedahigherdifference(50mmbeforeandaftertreatment)thannormallysatisfactory,adifference inVASof30-35mm, (Rowbothham2001), tomake sure that thegroupswouldnotbecometoosmall.

Calculations

In study I, theSPSSpackage(version11.5,SPSSInc.,Chicago,Illinois,USA)wasusedforallstatisticalcalculations.Meanandstandarddeviationswereusedtodescribedata.Differencesbetweengroupswerecalculatedusinganonparametrictestforindependentsamples(MannWhitneyU-test).Whendatawerecategorical,Chi-squaretestandFisher’sexacttestwereusedtoevaluatedifferencesbetweenthegroups.DifferencesbeforeandaftertreatmentwerecalculatedwithWilcoxonsignedranktest.P<0.05wasconsideredsignificant.

In study III,thepilotstudyconcerningultrasoundguidedarthroscopicshaving,the SPSS package (version 11.5) was used for all statistical calculations. TheWilcoxonsignedranktestwasusedtostudydifferencesinpatellartendonpainduringactivity, recordedby thepatientsonaVAS,beforeandafter treatment.P<0.05wasconsideredsignificant.

In study IV, the SPSS package (version 18.0) was used for all statisticalcalculations.MeanandSDwereusedtodescribedata.Differencesbetweenthegroups were calculated using a non-parametric test for independent samples(MannWhitneyU-test).P<0.05wasconsideredsignificant.

In study V,thelongtermfollowup,SPSSpackage(version21)wasusedforallstatisticalcalculations.Patientcharacteristicsaswellasdescriptivefrequenciesare presented as mean and range. The statistical analysis for paired tests ofboth continuous and ordinal variables was calculated with the non-parametric Wilcoxonsigned-ranktest.Differencesbetweengroupswerecalculatedusinganon-parametrictestforindependentsamples,MannWhitneyU-test.Spearmancorrelationwasusedforcorrelationanalysis.P<0.05wasconsideredsignificant.

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Paper ISclerosing injections to treat midportion Achilles tendinosis:arandomizedcontrolledstudyevaluatingtwodifferentconcentrationsof Polidocanol

Two to three ultrasound (US) and colour Doppler (CD)-guided injections ofthesclerosingsubstancepolidocanol(5mg/ml)hadbeendemonstratedtogivegoodclinicalresultsinpatientswithchronicmidportionAchillestendinopathy.Thisstudyaimedtoinvestigateifahigherconcentrationofpolidocanol(10mg/ml)would leadtoa lessnumberof treatments,and lowervolumes,neededforgood clinical results.Fifty-two consecutiveAchilles tendons (48patients)withchronicpainfultendinoticmidportionAchillestendinopathy,wererandomizedtotreatmentwithpolidocanol5mg/ml(groupA)or10mg/ml(groupB).

For basic data see table 1below(5mg/mlgroupA,10mg/mlgroupB)

Number

of Durationofsymptoms

VAS pain activity

tendons Male Female Age BMI in months at start

A 26 15 11 47.4±7.8 25.1±3.4 25.5±17.1 66.3±14.5 B 26 20 6 51.8±12.4 26.8±4.2 28.0±31.6 66.0±21.7

ns ns ns ns ns ns

All patients had structural tendon changes and neovascularisation corresponding tothetenderareaintheAchillesmidportion.US/CD-guidedsclerosinginjectionsweregiven,amaximumofthreetreatmentswith6–8weeksbetweentreatmentsessions before final evaluation. Patients who were not satisfied after threetreatmentsweregivenadditional treatmentswithpolidocanol10mg/ml,uptofive injections in totalwith6-8weeks inbetween.For evaluation, thepatientsrecordedtheseverityofAchillestendonpainduringactivityonavisualanaloguescale(VASforpain)andsatisfactionwiththeresultoftreatmentwasalsoassessed.

Clinical outcomes Group A, polidocanol(5mg/ml),meanVASpainafteronetothreetreatmentsdecreasedsignificantlyfrom66±14to25±28(P<0.05).

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Group B,polidocanol10mg/ml,meanVASpainafteronetothreetreatmentsdecreasedsignificantlyfrom66±21to24±31(P<0.05).At follow-up,mean 14months (range 2-35months) after three treatments,

18/26patientsingroupA(5mg/ml)and19/26patientsingroupB(10mg/ml)weresatisfiedwiththetreatmentandhadasignificantlyreducedleveloftendonpain(P<0.05).TherewasnosignificantdifferencebetweenthetwogroupsinVASpainduring

activity after treatment. Nor were any significant differences shown betweenthegroupsconcerningthenumberoftreatmentsgiven;groupA,2.6treatmentsandgroupB,2.5 treatmentsorconcerning the totalvolume injected;groupA,mean3.2±1.6mlandgroupBmean3.1±1.3mlbeforeagoodclinicalresultwasachieved—satisfiedpatient.

Additional outcome afteramaximumoffivesclerosinginjectionsGroupA;sixpatientswerenotsatisfiedafterthreetreatments.Theywereofferedand accepted treatment with additional injections of polidocanol (10mg/ml).After one additional injection therewere two patientswhowere not satisfied.ThesetwopatientsweresatisfiedafterafifthinjectionGroup B; seven patients were not satisfied after three treatments. They

were offered and accepted treatmentwith additional injections of polidocanol (10mg/ml). After one additional treatment, three patients were not satisfied.Thesethreepatientsweresatisfiedafterafifthinjection.Afterfiveinjectionsallpatients(groupAandgroupB)weresatisfiedwiththe

resultoftreatmentandtherewerenosignificantdifferencesbetweenthegroups.

ConclusionTheresultsindicatethattheeffectsbyinjectingpolidocanolwhenaimingattheentranceofthevesselsontheventralsideoftheAchillestendonmidportion,arenotrelatedtotheconcentration5mg/mlor10mg/mlofpolidocanol.Itseemsthatsmallvolumesofalowconcentrationofpolidocanol(5mg/ml),

injected under US/CD guidance are enough to cure the tendon pain in a high proportionofpatientswithmidportionAchillestendinopathy.Forclinicaluse,werecommendtheuseofpolidocanol5mg/mlwhentreating

chronicpainfulmidportionAchillestendinopathy.Furthermore,itappearsthatsmallvolumesofpolidocanolcouldbeusedforagoodclinicalresultwhentreatingmidportionAchillestendinopathywithUS/CDguidedsclerosinginjections.


Paper IIUltrasound – and Doppler-guided arthroscopic shaving to treat Jumper’s knee: a technical note

Inthistechnicalnotewepresentanewtechniqueforarthroscopictreatmentofchronicpainfulpatellar tendinopathy– jumper’sknee.Arthroscopicshaving isperformedwiththesimultaneousguidanceofUS/CD.Usingthistechnique,thetendon and the areaswith structural tendon changes and high blood flow arecontinuouslydemonstratedintheoperatingfield.Bythis,theshavingprocedurecanbemoreexactlyaddressedtotheareaofinterestonthedorsalsurfaceofthepatellartendonandthetraumatotheHoffa’sfatpadandthetendonisminimized.WewantedtofindaprocedurethatpermittedthesamepostoperativeregimenaspermittedafterUS/CD-guidedtreatmentwithsclerosinginjections.During development of this technique, standard knee arthroscopy was

performedexceptforthatweworkedwithtwomonitorsandUS/CD-guidancesimultaneously. We operated on altogether 39 patients with the diagnosisjumper’sknee–patellar tendinosis (37malesand2 females)withameanageof27yearsrange17–51).Therewerenosideeffectsorcomplicationsusingthisprocedure,andtheshort-termclinicalresultswerepromising.Nooutcomedataispresentedinthisnote.Theexactprocedureisdescribedin“treatmentmethodsinthisthesis”.Inconclusion,we foundthecombinedmethod,usingsimultaneousUS/CD-

guidanceduringthearthroscopicshavingtobepracticalandreliable.Itrendershigh precision and less tissue trauma, compared to performing arthroscopicshavingalone.

Paper III Treatment of Jumper’s knee: promising short-term results in a pilot studyusinganewarthroscopicapproachbasedonimagingfindings

Sclerosing injections targeting the area with neovessels and nerves on the dorsal sideofthepatellartendonhasbeendemonstratedshowpromisingclinicalresultsin patients with chronic painful jumper’s knee – patellar tendinopathy (PT).However,atimeconsumingandpainfultreatmentmethodwithameannumberofthreetreatmentswith6–8weeksinbetweenwereneededforagoodclinicalresult. This study aimed to evaluate amore radical approach to the areawithneovesselsandnervesbyusingUS/CD-guidedarthroscopicshaving.Wewantedtoseeifwecouldusethesameregimenaftersurgeryasweuseaftersclerosinginjection treatment. Two weeks after treatment allowing maximum patellartendonloadingactivity.Fifteeneliteandrecreationalathletes,12malesandthree

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femaleswithalongdurationofpainsymptomsfromtheirpatellartendonswereincluded.Allpatientshadtriedrestastreatmentwithoutanyeffectonthepainfulcondition.Forfurtherbasicdatasee table 2 below.

Basic data Mean(range)Age(years) 30(18-49)Height(cm) 184(172-200)Weight(kg) 81(62-96)Durationofsymptoms(months) 27(9-78)VAS pain activity at start 81(62-96)

In all patients US/CD examinations showed structural tendon changes with hypoechoic areas and a neovascularization on the dorsal side of the tendonwith vessels entering the tendon transversally. The increased blood flow wascorrespondingtothepainfulandtenderarea.AllpatientsweretreatedwithUS/CD-guidedarthroscopicshaving.Postoperativeregimeninstructedtothepatientswasasfollows.Day 1:Partialweight bearingwith crutches if needed. Start full non-weight

bearing rangeofmotionexercises.Days2–7:Startwalkingand lightbicyclingactivity. Light concentric and eccentric strength training for the quadricepsmuscleswasinstituted.Days8–14:Duringthesecondweekaftertreatment,thepatients were told to gradually increase their tendon loading activity with more sport specific training. No maximum jumping-, running-, or weight trainingactivity was allowed during the first two weeks. Two weeks postoperatively:Maximumpatellartendonloadingactivitycouldbestartediftherewasnomarkedmuscleatrophy.

OutcomesAtthefollow-up(mean6months)aftertreatment,therewasagoodclinicalresultin13/15tendons(6/8eliteathletes).Thesatisfiedpatientswerebacktoprevious(beforeonsetofsymptoms)sportactivitylevel,andtheamountofpainrecordedona visual analogue scale (VAS forpain)haddecreased significantly.VAS forpainhaddecreasedfrombeforesurgery;mean79(range35-100)toaftersurgery;mean12(range0-50),P<0.05.Anadditionaltelephonefollow-up13months(mean)postoperativelyshowed

thatthesame13/15werestillsatisfiedandactiveintheirsports,andthatthe2/15poorcaseswerestillnotsatisfiedwiththetreatment.


ConclusionIntheshort-termperspective,itseemsthatUS/CD-guidedarthroscopicshavingoftheareawithneovesselsandnervesonthedorsalsideofthetendoninpatientswith PT/JK can reduce the tendon pain during tendon loading activity and allowforthemajorityofpatientstorelativelyquicklyreturntopatellartendonloadingsportsactivityatcompetinglevel.Inthisstudythepatientswereallowedmaximumpatellartendonloadingacivityaftertwoweeks,iftheywanted.Therewerenopatientswithseverequadricepsatrophypre-operatively,butofcourse,suchpatientsmostlikelyneedalongerrehabilitationperiodbeforereturningtotheirsport.Theresultsmotivate furtherstudieswith largermaterialsand longtermfollow-up.

Paper IVSclerosing polidocanol injections or arthroscopic shaving to treat patellar tendinopathy/jumper’s knee? A randomised controlled study

Wewanted to compare the clinical effects after treatmentwithUS/CD-guidedsclerosing polidocanol injections and US/CD-guided arthroscopic shaving proximalpatellartendinopathy/jumper’sknee(PT/JK).Forty-five patients (52 tendons in 43males and two females) with US/CD

verifieddiagnosisofPT/JKwererandomlyassignedtotreatmentwithUS/CD-guidedsclerosingpolidocanol(10mg/ml)injections(groupA)orUS/CD-guidedarthroscopic shaving (group B). All patients were involved in patellar tendonloadingsportsorrecreationalactivities,andhadalongdurationofpainsymptomsfromtheproximalpatellartendonandsevenpatientshadbilateralPT/JK.

Nopatienthadanacuteonsetofpain.Thepatientshadtrieddifferenttypesoftreatmentbeforereferral,suchas;restformorethan3months(n=45),eccentrictraining (n=33) and NSAIDs (n=11). All patients were active, ranging fromrecreational (n=19) to competition level (n=26). All patients were diagnosed(clinicallyandbyUS/CDexamination)beforeinclusiontohavechronicpainfulPT/JKintheproximalpatellartendon.Inbothgroupsthepatientswereallowedfull weight bearing walking immediately after the treatment. Twoweeks aftertreatment the patients were told to gradually increase the patellar tendon load uptofullloading.Inthisstudytwofairlynewtreatmentmethodswerecomparedwhytherewasnospecificrehabilitationprotocol,orsettimeframes,precedingfulltendonloadingactivity.Follow-upsweredoneattwoweeks(GroupB),every6-8weeks(GroupAandB)andfurtherfollow-upsinbothgroupswerealsodoneat6and12months.Iftherewasremainingtendonpainduringsportactivityandaremaininghighbloodflowinatransversaldirectionintheregionwithstructural

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tendonchangesatfollow-upinthetendonstreatedwithsclerosingpolidocanolinjections,anotherinjectionwasgiven.Ifthepatientwasnotsatisfied6-8weeksaftercompletingthreeinjectionsessionsitwasconsideredasafailure.

Table 3 BasicdataforgroupAandgroupB(meanandSD).

Number of Follow-up

timeDurationofsymptoms

VAS pain activity

Group tendons Age in months in months at start A 26 27(7,6) 13,7(6,9) 20(10,4) 69(17,3) B 26 26,6(7,6) 12,9(7,8) 23,8(15,5) 76(13,6) ns ns ns ns

OutcomesIngroupA,onepatientdidnotcontinuethestudybecauseofpregnancy.IngroupB,allbutonepatientreceivedthe intendedtreatment.Before treatment, therewere no significant differences between the groups regarding age, duration ofsymptomsorpainatrestorduringpatellartendonloadingactivity.Atthefinalfollow-up,thepatientsinGroupA,meanfollow-uptime13,7months(SD6,9)hadsignificantlylowerVASscoresforpainatrestandduringpatellartendonloadingactivity,andweresignificantlymoresatisfiedwiththetreatmentresult,comparedtothepatientsin,GroupB,meanfollow-uptimeinmonths12,9(SD7,8).Therewerenosignificantdifferencesinthefollow-uptimebetweenthegroups.

Table 4,resultsatendpoint,meanandSD,significancep-value.

VAS pain rest VAS pain activity Satisfactionwithresult Group atfollow-up atfollow-up oftreatment(0-100) A 19.2(23.2) 41.1(28.5) 52.9(32.6)

B 5.0(8.3) 12.8(19.3) 86.8(20.8)

p/0.004 p/0.001 p/0.000


ConclusionTreatment outside the dorsal tendon alone is in strong contrast to the invasivemethods usedworldwide inwhich there is intratendinous excision ofmacroscopicallyabnormal tendontissue througha longitudinal tenotomy. It isinteresting that US-guided treatment outside the dorsal tendon seems to produce markedly better clinical results than have been reported from intratendinoussurgery. Also, considering the rehabilitation after treatment, extratendinousproceduresareassociatedwithapossibilityofaveryquick(6–8weeks)returntofulltendonloadingactivity,whereasintratendinousproceduresoftenrequireaverylong(4–12months)rehabilitationperiod.Thecurrentstudyonlypresentsshort-termresults,butitseemspromising.However,thereisaneedforfurtherstudies.In conclusion, both treatment with US/CD-guided sclerosing polidocanol

injections and US/CD-guided arthroscopic shaving showed good clinical results inpatientswithchronicpainfulpatellartendinopathy.Patientstreatedwiththenew surgical procedure US/CD-guided arthroscopic shaving had significantlyless pain and they were more satisfied with the treatment results. Since thearthroscopicprocedure isaone-stage treatment, return tosportswas faster inthisgroup.

Paper V – manuscript

Treatment of patellar tendinopathy with sclerosing injections or ultrasound-guided arthroscopic shaving – a long term follow-up ofultrasoundfindingsandclinicalresults

Treatment of PT/JK knee with US-guided sclerosing injections or US-guidedarthroscopic shaving has shown good clinical short-term results. Formerstudiesindicatethatthetendonstayssonographicallyabnormalaftersuccessfultreatment.In this follow-up study a total of 43 patients (41 males/2 females) with

57 treated tendons chose to participate. They were former participants in aprospective randomized trial evaluating treatment with US/CD-guided sclerosing injections (Group A) and US/CD-guided arthroscopic shaving (group B), andanadditionalninepatients fromapreviouspilot studyevaluating theUS/CD-guidedarthroscopic shavingmethod (GroupB), forchronicpainfulPT/JK.Allpatients included in this study came for an evaluationwithUS/CD.They alsoscoredtheirlevelofpatellartendonpainduringtheirspecificsportorrecreationalactivity,andatrest,ona100mmVAS-scale.Self-reportedsatisfactionwiththeresultoftreatmentwasalsoscored(0-100).Allscoreswerecomparedwiththe

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correspondingscoresatbaseline,beforetreatmentandattheshorttermfollow-up(mean12months).

Table 5 BasicdataGroupA–sclerosinginjections,GroupB–arthroscopicprocedure.Durationandtimepresentedinmonths.

p - valueGroup A Group B

Age(years) 27,6(9,7) 27,3(7,8) 0,456Length(cm) 182(6,3) 182(5,1) 0,252Weight(kg) 77,5(8,1) 79,6(8,5) 0,213Durationofsymptoms 21,1(11,8) 22,7(17,4) 0,37Timetofollow-up 14,2(7,5) 10,7(6,4) 0,111Time to endpoint 43,7(8,3) 48,8(9,9) 0,065

mean(SD) mean(SD) significance

Thesameequipmentwasusedforallexaminations,andthesameexperiencedsonographerperformedallUS/CDevaluationsatbaseline,atshorttermfollow-up and at final follow-up. Intra observer reliability for evaluation of tendonstructure and neovascularization (localized high blood flow) had been tested,as well as reproducibility for measures of thickness. US investigations wereperformedaccordingtoaroutineprotocolforinvestigationofthepatellartendon.Patientswere ina supinepositionwithknees stretchedand fully relaxed.US/CDregistrationsweretakeninbothlongitudinalandtransversalplane.Tendonthickness(APdistance)wasmeasuredatthewidestpartoftheproximalpatellartendon; in the centre of themost tendinotic region, in the longitudinal plane.Tendon structure and neovascularisation (localized high blood flow) wereevaluated with the same criteria that were used at baseline and at short term follow-up,accordingtoamodifiedÖhbergmodel.Tendonstructure;0–normalstructure(homogenousechogenicity),1–light

structural changes (discrete hypo-echogenic areas), 2 – moderate structuralchanges(somewelldefinedhypo-echogenicareas),3–severestructuralchanges(extendedhypo-echogenicareas).Neovascularisation (high blood flow); 0 – no visible vessels, 1 – mild

neovascularisation (solitary transversal vessels in the proximal/ventral part),2–moderateneovascularisation(moderatequantity,mostly transversal in theproximalpart),3–severeneovascularization(several,mostlyhorizontal,vesselsspreadinthewholedepthandmoredistallyinthetendon).


OutcomesAtfinalfollow-up(endpoint),inbothgroupstherewasasignificantdecreaseinVASduringactivity,amongpatientstreatedwithsclerosinginjections,from64to17and74%weresatisfied,andamongpatientstreatedwitharthroscopicshavingfrom 77 to 13 and 80% were satisfied. There were no longer any significantdifferencesinpainaccordingtoVASbetweenthegroups.Asignificantcorrelation,bothatfollow-upandatendpoint,betweenlowlocal

bloodflowandlowpainmeasuredwithVASduringactivity(FU0,40p=0,01;EP0,48p<0,01)andhighpatient-satisfaction(FU0,45p<0,01;EP0,56p<0,001)wasfound.IngroupB,acorrelationwasfoundatfollow-upbetweenlargetendonthicknessandhighVASforpainatrest(0,66p<0,01).

At endpoint tendon structure had improved and CD detectable local blood flow had diminished significantly in both groups. Therewas also a significantdecreaseinAPthicknessoftheproximalpatellartendoningroupBbutnot ingroupA.Sonographically,amorenormal tendonstructure,wasseenearlier ingroupB.Interestingly,initiallyasignificantincreaseinproximalpatellartendonAPthicknesswasseen inGroupA,butat thefinal follow-upAPthicknesswassimilarasbeforetreatment.

ConclusionsTherewere good, and similar, clinical resultswith bothmethods at endpoint.Bothtreatmentsshowedgoodresultsconcerningpainreductionduringactivity.However,theUS/CD-guidedarthroscopicprocedurerenderedaquickerreturntofullactivityandsports.ThelongtermresultsinGroupBwerethesameasintheshorttermfollow-upstudy.InGroupAclinicalresultshadimprovedcomparedwiththeresultspresentedintheshorttermfollow-upstudy,tothesamelevelastheresultsofGroupB.AttheendpointtheonlyfactorwithremainingdifferencebetweenthetwomethodswastheAPthicknessinthetendon,wherethetendonwas significantly thinnerandsongraphically “morenormalised” in the surgicalgroup.Aninterestingobservationwasthefactthattheamountofincreasedbloodflow

wasthefirstandquickestparametertochangeinthesurgicalgroupwhoreturnedtofullandpainlessactivityfastestofthetwogroups.Thisfactamongothersinthisstudyleavesalotofquestionsunsolved,buttherearesomeindicationsthatthestructuralchangesandtheamountofneovascularizationwithinthetendontissuemightcorrelatewithclinicaloutcomeandopensforfurtherinvestigationsinthisdirection.

59 59

DIS

CU

SSIO

NVII


General discussion and clinical considerationsIt has been said that “treatment effectiveness is inversely proportional to thenumber of available treatment choices”. In my opinion this is very true forchronic painful tendinopathy. The present thesis has focused on two differentnew treatment methods for chronic painful tendinotic midportion Achillestendinopathyandchronicpainfultendinoticproximalpatellartendinopathywithaspecialinterestinthelaterofthetwo.Tendinopathies are amajor problem in sportsmedicine. The prevalence of

Achillestendinopathyinrunnershasbeenestimatedtobe11%(Jamesetal.1978)and20%of knee injuriespresentingat a sports clinichavebeendiagnosedaspatellartendinopathy(Kannusetal.1987).Fiftypercentofpatientswithpatellartendinopathy have been reported to give up their sports career due to their knee problem(Kettunenetal.2002).InaretrospectivestudybyCooketal.(1997)theyshowed thatoneoutof threeathletesvisitingsportsmedicineclinicswith thisdiagnosiswasunabletoreturntotheirsportswithinsixmonths.In general, it is very important to establish the underlying pathology of a

disease.Lackofscientificinformationmakesthedevelopmentofevidence-basedtreatmentmoreorlessimpossible.The pathology of tendinopathy is still relatively poorly understood. It is

generally accepted though that in the chronically injured tendon the repair capacityofthetendonisexceeded.Chronicpainfultendinopathyisconsideredtobeadegenerativecondition,oratleastonewithafailedhealingresponsewithalackofatrueinflammatoryinfiltrateandresponse.Consequentlyithasbecomeincreasinglyrecognisedthatanti-inflammatorystrategiesare largely ineffectiveinthemanagementofchronictendonconditions.Supportingthehypothesisthattendinopathydevelopsduetoafailedchemicalhealingresponsecouldinducinganewchemicalreactionbesufficienttoinduceahealing?Anincreasedinterestinthedevelopmentandresultsofbasicscienceoftendinopathieshasbeenseenamongstclinicians.However,thereisstillaneedforfurtherresearch.Radiologically, both US andMRI are being reported to correspond well to

histopathologicalfindings(Khanetal.1998;Alfredson2005b;Peersetal.2005).In close relation to the high blood flow outside the tendinotic chronic painfulAchillesandpatellartendons,sensoryandsympatheticnerveshavebeenfoundinimmunohistochemicalanalysesofbiopsies(Danielsson2007).Regionswithlocalizedhighbloodflow,shownwithCD,correspondingtothe

painfulandtenderareainthechronicpainfultendonmaybeofimportanceoratleasttosomeextentexplainthereasonforpainandimpairedfunction.However,the total diagnostic picture is even more complicated, especially concerningthepatellar tendon.For example, in a studybasedon320patellar tendons inasymptomatic elite athletes representing different sportsUS hypoechoic areas

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were present in 22 % of these pain less tendons. In a control group of non-athletic individuals, only 4% of asymptomatic tendons showed these changes(Cooketal.1998).ConcerningtheAchillestendontherearealsosomereportsonintratendinouschangesverifiedwithUSandMRIinpatientswithoutcomplaints(Haimsetal.2000;Emersonetal.2010).However,inonestudybyPeersetal.(2003) theydiscuss and evaluate the correlationbetweenPDfindings and theclinicalseverityinAchillestendinopathy.Thepathologicalfindingsarenotalwaysclearly described though. For example in cadaveric studies it is impossible toevaluatetheexistenceofhighbloodflowandCDisnotusedinallstudies.Whenreviewingtheliteratureoneproblemisthelackofconsistentterminologyrelatingtothechronicpainfulconditionsintendons.Theterminologycanbeconfusingleadingtodifficultieswhencomparingdifferentscientificstudies.

Midportion Achilles tendinopathyAnabundantamountofdifferent treatmentmodalitieshasbeendeveloped fortreatment of chronic midportion Achilles tendinopathy. Concerning injectiontreatmentsdifferentsubstancesandtechniquesareinuse.Therationalebehindthesetreatmentsmostoftenlackscientificevidence,andtheexactlocationoftheinjection isnotalwaysclearlydescribed.Ingeneral, thegoalof treatment is torelievesymptoms.

In this thesis we evaluated the injection treatment with the sclerosing substance polidocanol for chronic painful tendinotic midportion Achilles tendinopathy(studyI).Apilotstudyhadshownpromisingresults(Öhbergetal.2002).Twoto threeUS/CD-guided injectionsofpolidocanol (5mg/ml)wasdemonstratedtogivegoodclinicalresultsinahighproportionofthepatients.Thetreatmentispainfulandinmanycasesittakesarelativelylongtimetorecover,sincetherewas 6-8 weeks between the treatment sessions. It seemed logical to questionwhethertreatmentwithahigherconcentrationofpolidocanol,10mg/mlthanthepreviouslyused5mg/mlcouldleadtoalessnumberoftreatmentsneededforgoodclinicalresults.We very strictly followed the initial method description and we were very

strictwithourinclusioncriteria.Weinjectedatthemost2mlofpolidocanolpertreatmentsessionaimingattheentranceofthevesselsontheventralsideofthetendon.Patientswerenotconsideredfortreatment,ifanyoftheformerdescribedcriteriawasmissing,whichmeansthatatendoncouldshowUS/CDfindingsbutifthepatientdidnotexperienceanyremainingpainortendernesswerefrainedfromfurther injectionsand justprospectively followed thepatient.Thegoodresultsinourstudy indicate that smallvolumesofa lowconcentrationofpolidocanol(5 mg/ml) injected under US/CD-guidance seem to be an alternative to curethetendonpaininamanypatientswithchronicpainfultendinoticmidportion


Achillestendinopathy.Noadverseeffectswerefound.Thedesignofthestudyhasafewlimitationsthatwillbediscussedlateron.Duringtheyearstheinjectionofpolidocanolhasbeenasubjectfordebatein

manycontexts.Unfortunately,thereisalackofprospectiverandomizedcontrolledstudies.However,inoneretrospectivefollow-upstudyusingtheinitiallydescribedtreatment method the authors reported sclerosing injections to be a promising alternative for treating patients with chronic painful tendinotic midportionAchillestendinopathy(Clementsonetal.2008).Inanotherretrospectivestudyrelativelypoorresultsweredemonstratedaftersclerosingpolidocanolinjections.Unfortunately, these authors did not follow the initial treatment methoddescribedforUS-guidedsclerosingpolidocanolinjections.Basedontheirresultstheydebate“thebeneficialvalueofsclerosingtheneovascularizationinpatientswithmidportionAchillestendinopathy”(vanSterkenburgetal.2010).Concerning the sclerosing polidocanol injection treatment method, it is of

utmost importance to make sure that the original method description is properly followed.Itisnoteasytoperform.Anotherdrawbackofthemethodisthatyouneedtobetwopersonstoperformtheinjectionsandevaluations.Preferablyonewith orthopedic expertise and one US technician or radiologist to enable a correct interpretationoftheUS/CDfindingsandtoaccuratelymanagingtopositiontheinjectionneedlewithUS/CD-guidance.Thelearningcurveisnotverylongfromatechnicalpointofview.Howtojudgeandhandletheclinicalaspectsthoughtakesfairlylongtimeandalargenumberofpatientsareneeded.Italsoseemstobeofutmostimportancetohavestrictindicationsfortreatment.

Wehaveseenpatientswhere“togetridofthevessels”wastheindication,patientswhere largevolumeswere injected (5–10mlper treatment), andpatientswhowereinjectedeverysecondweek.Underthesecircumstancesitisnotpossibletocomparetheresultswiththoseoftheoriginalmethod.Moreover,thismaygivethetechnique“badreputation”,sincetheresultshavebeenunsatisfactoryduetonotfollowingtheoriginaldescriptionofhowtoperformsclerosingpolidocanolinjections.Itisimportanttobeawareofthatpolidocanolcanspreadintothesofttissueandcommunicantveinsinthelowerlegmightbeatinjuryrisk.There has to be a focus on future randomized controlled trials to further

evaluate this method. Preferably using eccentric training in a control groupsince eccentric training today has the most evidence concerning non-operative treatmentsofAchilles tendinopathy (Wasielewski2007).Wefind the injectiontreatmentmethodofpolidocanolverygood,though,ifperformedcorrectly.

Patellar tendinopathyPatellar tendinopathy/Jumper’sknee is themainfocusof this thesis.Hitherto,there is no golden standard in the treatment of patients with jumper´s knee.

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Surgical methods vary considerably between different clinics and scientificevidence is lacking for both non-operative and operative treatments (Khan etal. 1998; Cook et al. 2001a). During recent years a number of review articlesconcerning the injection treatment (vanArketal.2011;Wileyetal.2013)andacritical reviewof treatmentoptions (Gaidaetal.2011)aswellasa reviewofrandomizedcontrolledtrials(Nilsson-Helanderetal.2012)havebeenpublished,though. All these publications conclude that eccentric training still appears tobe the treatment of choice for patients suffering from patellar tendinopathy.However, the type of exercise, the frequency, load anddosage still need to befurtheranalyzed.Othertreatmentmethods,suchassurgicaltreatment,sclerosinginjections and shockwave therapy also need to be further investigated beforeoptimal recommendations can be made about the treatment of choice. Thismeans that the situation today is almost the same as some ten years ago despite moreknowledgeaboutthebasicsinthepainfultendon.Allexistingtreatmentmodelsaretimeconsuming,oftenpainfulandleadsto

varyingclinicalresults.Ourfocuswastofindatreatmentmethodaddressingthenewknowledgeabout thepathology in theproximaldorsalpartof thechronicpainful impairingtendinoticpatellartendon.Aonestageprocedurewithafastreturntopatellarloadingactivitywasourgoal.We invented a new method, US/CD-guided arthroscopic shaving, and

believed that with simultaneous US/CD there could be a more exact localization of the pain producing tissue.We believed that this new arthroscopic shavingwith simultaneousguidanceofUS/CDcouldbeanalternative to treatpatellartendinopathy(studyII).ThetraumatotheHoffa´sfatpadandthetendonwouldbeminimized.Arthroscopyitselfleadstogreatadvantages.Itiscosteffectiveandeasy to perform in local anesthesia. It permits an evaluation of the knee jointinanoutstandingway.Anotheradvantageoftheintraarticularevaluationisthefact thatMRI,which iscostlyand inferior toarthroscopy indiagnosticaspectsconcerning for example plicaes, cartilage injuries etc, might not be needed.Technically,ournewsurgicalmethodwasfairlyeasytoperformandthevisibilitywasreallygoodintheUSmonitor.TheDopplerfunctioncould,ofcourse,onlybeusedintermittently,sinceitdetectsallmovements–liketheoscillationoftheshaver.Duringtheevaluationofthemethodwefoundgoodresultsinthepilotstudyandnoadverseeffectsof theUS/CD-guidedarthroscopy (study III).Wecouldletthepatientsgobacktofull tendonloadingactivityapproximately6-8weeksaftertheprocedure.Onthenegativeside,youhavetobepreparedtobeguidedsolelybytheUSoncestartingtheshavingprocedure,sincetherewillbeableedinginthejointobstructingthearthroscopicvisibility.Thereisaneedforanextrapairofhands,anassistant,handlingtheUSprobe.Pilotstudieshasshownpromisingresultsofsclerosinginjections(Alfredson


etal.2005a;Hoksrudetal.2006).InourstudyIVandVwewantedtocomparetheresultsof these twofairlynewtreatmentmethods.InstudyIV,as instudyIII, we were very strict about the clinical findings and symptoms as with theUS/CD findings for inclusion. One big problem in research on PT/JK is thedifferentnomenclaturethatisusedintheliterature.WhengivingthesclerosinginjectionswewereasstrictinindicationsaswiththeAchillestendons.Onlysmallvolumes,amaximumof2mlpertreatmentsessionaddressingtheentranceofthetransversalvesselsintothetendononthedorsalproximalpartofthetendonwereinjected.Inthepilotstudymentionedabove(Hoksrudetal.2006),therewas only 3-5 weeks between the treatments, which is not in accordance withthe initialmethod described.We choose to follow the initial description with6-8weeksbetween treatment sessions.Whenusing this treatment forpatellartendinosis,highvolumesmightleadtointraarticulardeposition,causingsynovitisandfibrosis.Italsoseemstobecrucialtobeveryspecificwhenitcomestotheinjectiontechnique,whiledepositinginjectionsintotheIFPcancauseintolerableaccentuatedpain(Bennelletal.2004;Hodgesetal.2009).US/CD-guidanceisanecessity.InstudyIVwefoundthatbothtreatmentwithUS/CD-guidedsclerosingpolidocanol injections and arthroscopic shaving showed good clinical results.Interestinglyenough,instudyV,thelong-termfollow-up,showedsimilarlygoodclinical resultswith bothmethods at endpoint. The only remaining differencebetweenthetwomethodswastheAPthicknessofthetendon.Thetendonwassignificantlythinnerandsongraphically“morenormalised”inthesurgicalgroup.Anotherinterestingobservationisthefactthattheamountofincreasedblood

flowwasthefirstparametertochangeinthesurgicalgroup.Theyalsoreturnedto full and painless activity fastest of the two groups. This fact among othersin studyV leaves a lot of questionsunsolved.There are some indications thatthe structural changes and amount of neovascularization within the tendontissuemightcorrelatewithclinicaloutcomeoftreatment.Thesefindings,beingcontradictorytothoseofformerresearchopensforanewthinkingandaneedforfurtherinvestigationsinthisdirection.A recent study from Hoksrud et al. evaluating sclerosing treatment with

polidocanol in 101patientswithpatellar tendinopathy showed that only a fewpatientswerecured,andthemajorityofpatientsstillreportedsubstantialpainandshowedreducedfunctionaftera24monthfollow-up(Hoksrudetal.2012).Inourstudieswedidnotobjectivelymeasurefunctionthough,butwemeasuredreturntopainlessactivity.Intheirstudy,theytreatedthepatientswithintervalsof 4-6weeks and injected the vessels entering from the ventral side.One canspeculate whether their result really is comparable with sclerosing injections targetingthevesselsandpathologyonthedorsalsideof thetendon.Theyalsostate thatabout two thirdsof thepatientswith jumper'skneecanbeexpected

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tohave structural tendon changeswithneovascularization, and that therewasno relationshipbetween changes inUS characteristics andknee function aftersclerosing treatment (Hoksrud et al. 2008). This enhances the importance ofusingthesamenomenclature.Theauthorsrecruitedpatientsamongeliteathleteswithaclinicaldiagnosisofjumper'skneeforthisstudy,whichmayexplainthatonethirdofthepatientsdidnothaveanydetectableUSchangesinthepatellartendon.PatientswereexaminedwithUS/CDatbaseline.Patientswithstructuralchanges and neovascularization received sclerosing injections, the US/CDexaminationswereperformed12-15monthsafterthesclerosingtreatment,whichmaybetooearlytodetectthepossiblechangesthatwefoundinstudyV.ForchronicpainfultendinoticpatellartendinopathytheonestageUS-guided

arthroscopicprocedureseemstobeagoodalternative.Itneedsfurtherstudiesforevaluation,ofcourse.Thearthroscopicprocedureisavaluableoption,despitetheeffectivenessshownwithsclerosinginjectionsinthestudybyHoksrudetal(2011).Onethirdoftheirpatientschosetoseekadditionaltreatment,arthroscopicsurgeryduringthe44-monthfollow-upperiod,though.Sclerosinginjectiontreatmentmightbeanoption,butitisimportanttokeepin

mindthatitisapainfultreatmentmethodoftentakingalongtimebeforesatisfactoryresultsareachieved.ForchronicpainfultendinoticpatellartendinopathytheonestageUS-guidedarthroscopicprocedurethereforemaybeabetteroption.

Gender and tendonsIn females the collagen synthesis rate is reported to be lower than in males(Milleretal.2007).ThesynthesisofcollagentypeIalsoseemstobeaffectedbymeno-pausal hormone alterations with a decrease in collagen type I leading to lesstensilestrength(Moallietal.2004).Aftersurgeryfemalesgenerallyhaveaprolongedperiodofcomplicationsandrecovery,comparedtomalesundergoingthe same surgical treatment (Maffulli et al. 2008). Interestingly in one studyevaluatingeccentrictraininginpatientswithmidportionAchillestendinosis,thefemalesshowedpoorerresults thanthemales(Fahlströmetal.2003).ForthemidportionAchillestendinopathyitisnowadaysdiscussedwhetheritisapartofsomemetabolicsyndromeinsteadofbeingprimarilyanoveruseinjury.InpatientswithasymptomaticAchillestendonpathologyadifferenceinfatdistributionwasfoundbetweenmalesandfemales.Thisrecentcohortstudyreportedthatmaleshadpredominantlyacentralfatdistributionandfemalesaperipheraldistributionof fat. These findingsmight point in a direction to a relation between tendonpathologyandfatmetabolism,orinsulinresistanceinmales(Gaidaetal.2010).


US and Doppler changes in the tendon correlatingtoclinicalfindingsandsymptomsTendinotictendonsshowadegenerationoftheextracellularmatrix(Riley2005)with disordered arrangement of collagen fibers, increased vascularity (Khanet al. 1999). Changes in vascularity have been suggested to be involved in thedevelopmentofpatellartendinosis(Khanetal.1998).Structuralabnormalitiesin patellar tendons seen in US can be detected in painless individuals in high riskpopulations.ThepresenceofUSchangescanbethreetimeshigherthanthepresenceofclinicalsymptoms.Eveninathletes,notregularlyphysicallyactive,asymptomaticcontrols,suchstructuralchangeswereshownin10%ofallpainlesspatellartendons(Gisslenetal.2005).Inthesecontrols,Dopplertechniquedidnotshowanincreaseinvascularity(Gisslenetal.2005).However,anincreaseinvascularitycanbedetectedinasymptomaticindividualsinhighrisksports(Cooketal.2005). Studiesonpatellar tendonsusingUS/CD/PDhavedemonstratedanincreasedvascularity,interpretedasneovascularization,withinanddorsaltotheareawithstructuraltendinoticchanges(Cooketal.2004b;Alfredsonetal.2005;Gisslenetal.2005).Anassociationhasbeennotedbetweenthedegreeofsuchpathologicalvascularityand the levelofpain inpatellar tendinosis (Cooketal.2005).Incasesofclinicallydiagnosed“Jumper’sknee”itseemsthatthisincreasedvascularityinCDisfoundinthemajorityofindividuals(Gisslenetal.2005;Hoksrudetal.2008).Thelinkbetweenpainsymptomsandincreasedbloodflowhasnotyetbeenfound.Thevessels,whichareconsideredneovessels,arebysomeauthorsdescribedtoberandomlyoriented(Khanetal.1999),whileothershavenotedanincreasealsointhenumberofvesselsalignedinparallelwiththetendonfibers(Maffullietal.2000).Thesecontradictoryfindingsconcerningthebloodvesselsarehighlydiscussable.BasedonclinicalexperienceIwouldliketosuggestthatthetransversevesselscouldhaveacorrelationtotheseverityofpain,functionandtheneurogeniccomponent,whilstthevesselsparalleltothetendonfibersarecorrelatedwithstiffnessbeingacomponentofahealingprocess.The importance of blood flow in terms of pain is puzzling. However, the

treatmentmethodsinthisthesisonlytargettheareawithincreasedbloodflow.The sclerosing injections and the US-guided arthroscopic shaving immediately reducethe increasedbloodflow(Alfredsonetal.2005a;Hoksrudetal. 2006)and the effect of treatment is immediate concerning the CD findings. Whenyou study the treated tendon, directly after treatment, after some time youcan often visualize formerly not detectable vessels with CD, intratendinouslyin a longitudinal direction in the full thickness of the tendon. There is sparseinformationinallstudiesconcerningtendonpathologyandabouttheactualCDfindings,mostlyonlytheexistenceofbloodflowornot,isdiscussed.Itcouldbeproposedthatthereisaneedforthequalityofbloodflow(intermsofdirection,

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extent,severityandentrancesiteofthevessels)tobedescribedinstudieswhentreatingtendinotictendinopathy.Toourknowledgethereisonlyonestudysuggestingthatincreasedbloodflow

after treatment could indicate a healing response (Alfredson et al. 2006) and.Furthermore,thereisapilotstudyonpatientswithchronicmidportionAchillestendinopathy.Itshowsthatpatientswithgoodclinicalresultsafter12weeksofeccentrictrainingshowamorenormalizedtendonanddecreasedbloodflowinUS/CDthanbeforetreatment(Öhbergatal.2004).TheresultsinstudyVinthisthesissuggestthatfurtherresearchinthisdirectioncouldleadusforwardtoabetterunderstandingofthetreatmentresponsesfromaclinicalpointofview.The patients often complain about postfunctional and morning stiffness,

alsosharpintolerableimpairingpainduringactivity,andsometimesalsosharppain at rest. This is a characteristic sign of chronicAchilles tendinopathy and“Jumper’sknee”.Itissuggested,themorepainduringactivityandstiffness,thepoorerstageofthetendoncondition(Cooketal.2002,Peersetal.2003).Thisisalsodiscussable,sincesometimesincreasedstiffnessisseenwhenthesharppainisdecreased.Whensharppainlessensinfrequencyandstiffnessincreasesonecouldspeculatewhetherthiscouldbeasignofahealingprocess.Iwouldliketoseparatesharppainfromstiffnessinfuturestudies,sinceinmyexperiencethestiffnessappearswhenthetendonisfilledwithlongitudinalvesselsinitswholedepthandthetendoniswiderinitswholelength.

Sonographically,thestructurenormallylookslesspathologicalatthisstageofsymptoms.Ifthetreatmentof“tendonpain”inthetendinotictendonissuccessful,the tendonseems tonormalize inbothwidthand structure if the treatment isstrictly extratendinous. If the treatment is intratendinous, maybe the tendonnever normalizes. A long-term follow-up study revealed persistent structural

US/CD findings in the same tendinotic midportion Achilles tendon before and three months after sclerosing injection. To the left, transversal blood vessels, entering the ven-tral side of the painful tendon, the patient experiences sharp impairing pain during ADL. To the right blood vessels, in the whole depth of the tendon in an unorganized fashion, patient experiencing stiffness during ADL but no sharp impairing pain.


abnormalitiesandthickeningofthetendon13yearsafterintratendinoussurgeryforAchillestendinopathy,whereasallpatientsweresatisfiedwiththeresultsandwentbacktoAchillestendonloadingactivitieswithoutrestrictions(Alfredsonetal.2009).

SomefinalclinicalreflectionsIn midportion Achilles tendinopathy US/CD-guided sclerosing injections with polidocanolseemstobeanoptionifnon-operativetreatmentfails.Performingsclerosinginjectionsaccordingtotheinitialmethoddescribedis,however,crucial.“Toomuchtoosoon”isnottheidea.Still,eccentrictrainingshouldbetriedasaprimaryinterventionaccordingtotheliterature.Iffailureafter3-4monthsandUS/CDfindings indicate a picture of ventral hypoechoic areas and transversalvessels corresponding with the tenderness in the Achilles tendon, and if thepatient still experience sharp pain during activity or at rest sclerosing injections couldbe tried.However, let the tendonget3-4monthsbetweenthe treatmentsessions. If there is a lack of sharp pain, though, and an increase in stiffness,despitepathologicalUS/CDfindings,bepatient,thetendonwillprobablyheal.Wesuggestnottomixdifferenttreatments.InchronicpainfultendinoticpatellartendinopathyIwouldsuggestanUS/CD

examinationinordertoconfirmthediagnosis.Startthetreatmentwitheccentrictrainingincludingadeclineboard,andtakethepatientawayfromtheirsportfor6-8weeks.Makea follow-upwithanUS/CDexaminationafter8-10weeks. Ifnon-operativetreatmentfails,ifthereisalackofa“healingresponse”accordingtoUS/CD,andifthereisstillasharppainduringactivityIwouldsuggestthenewUS-guidedarthroscopicshavingapproach.Inourlargermaterialitisshownthattwothirdsofthepatientshaveassociated

pathologyintraarticularlynotvisibleonMRI(unpublisheddata),whichmakesthearthroscopyevenmoreappealing.Notonlycanyoutreatthetendon,youcanalsogetaproperviewoftheintraarticularstate.

Both treatment with US/CD-guided sclerosing polidocanol injections and US/CD-guided arthroscopic shaving have shown good clinical results in patients with chronicpainfulpatellartendinopathy.Inathletesthatareduringtheircompetitiveseasoninjectiontreatmentcouldbeanoptiontoreducepain.Ifproceedingwithsurgicaltreatment,beawarenottoresecttoomuchofthe

Hoffa´sfatpad,sinceventralimpingementshouldbeavoided.TheIFPisaverypotentstructure.Forexample,IFPpainhasbeenexperimentallymodelledwithinjection of hypertonic saline into the fat pad. The induced pain peaked 2–3minutesafterinjectionatanaverageintensitybetween5.5and5.8outof10,andgradually declined over 15minutes (Bennell et al. 2004;Hodges et al. 2009).Reportedpainwasnotonlyinferiorpatellabutalsodeepandretropatellarwith

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somereportingmedial thighpain.During theperiodofpain, thecoordinationof thequadricepswasalteredwithadelayedonsetofvastusmedialisobliquus(VMO) activity (Hodges et al. 2009). The EMG activity of both the VMO andthevastus lateralismusclesdecreasedinmagnitude.Thismaysupportthefactthat patients experiencing long-term anterior knee pain are weak and slow in theirquadricepsmuscle,especiallyVMO.Even ifwedidnothavea specificrehabilitation protocol after surgery this is recommendable and should bemandatorywhentreatingpatientsandnotperformingcomparingstudies.Mostofthepatientsareveryweakintheirquadricepsandshowimpairedkneejointcontrol.Fullpatellartendonloadingseemstobealright6-8weeksaftersurgicalinterventionconcerningthepatellartendon.Inordertoperformintheirsports,though,muscularstrengthandmuscularcontrolhavetobeinfocusaftersurgery,whichcanbetimeconsuming.Studiesconcerningrehabilitationprotocols,asacomplementtotheUS-guided

shavingprocedure,havetobeperformed.

Strengths and limitationsOnemajorstrengthinthesestudiesisthefactthatthesameUStechnicianhasconducted all US/CD examinations. Studies using US, in the field of tendonresearch, often refers to tendon thickness, structural changes and amount ofvisiblebloodflow.However,thereliabilityofthesemeasurementsandthequalityof the evaluations are not always reported. Intraobserver reliability have beenaddressedinourstudies.WeconsistenlyhaveusedtheÖhbergscoretodescribetheUS/CDfindingsandalsoall imageshavebeendocumented in thepatientsregularchartinourjournalsystem.Furthermore,thesameorthopaedicsurgeon(LW) has seen all the patients at inclusion, operated on and injected all thepatientstogetherwiththesameUStechnician.Thefollow-upshavebeencarriedoutindependentlyoftheorthopaedicsurgeon.Another strength is the fact thatwewere very strict to followour inclusion

criterias and definitions of pathological findings. We also followed the initialdescriptionofhowtoperformthesclerosinginjectionstothepoint.Developingatotallynewtreatmentmethod,US/CDguidedkneearthroscopyI

believealsocanbeconsideredasastrengthinthisthesis.The“cross-overdesign”instudyIandIVmaybeseenasstudylimitations.If

these studies should be repeated today I would probably avoid the “cross-over design”.However,fromanethicalpointofviewitmaybedoubtfulifitwouldbefair to thepatients,especiallywhen itcomestostudyIV,whereonetreatmentseemedmuchmoresuperiorintimeandpainduringtreatment.Therefore,itmaybemoreappropriatetohavethepatientsinfocus.Inotherstudies,patientswithpatellartendinopathyreceivingsclerosinginjectionshavesoughtotherclinicsfor


anarthroscopicinterventionthemselvesbeforeafinalfollow-upiftheinjectiontreatmentfails.Bythe“cross-overdesign”instudyIVwewereableto“keepthepatientsunderourwings”andprospectivelyfollowthemoveralongerperiodoftime.Another study limitation could be thatwe did not use a specific activity or

functionalscoresuchastheVISA-AorVISA-Pscore(VictorianInstituteofSportAssessment),forinstance.FortheAchillestendonsinstudyIourintentionwastousetheVISA-Ascore,butthefunctionofthepatientsweresopoorthattheydidnotunderstandthequestionnaireandmostofthemrefrainedfromfillingitin.ThiswasthereasonfornotusingtheVISA-Ascore.Instead,wefocusedonevaluating Achilles tendon pain during each patient´s specific recreational orsportactivityaswellasatrest.ItislikelytobelievethattheuseofVASforpainratingsandpatientreportsabouthowsatisfiedtheyarewiththeirtreatmentmaybe appropriate tools for evaluating clinical outcomeof the injection treatmentwithpolidocanolinstudyI.IntermsofthepatientswithPT/JK,itwasamistakenottousetheVISA-P

score. Itwouldhavebeengood tobeable to easier compare the resultsof thetreatmentstootherstudies.However,alsoforthisgroupofpatientswebelievethat evaluating patellar tendon pain during their chosen specific recreationalor sport activity together with satisfaction with the treatment results may beappropriatetoolswhenevaluatingtheclinicaloutcomeofthetreatments.A possible limitationmay be that the sample sizes of our groups are fairly

small.However,whencalculatingthepowerofthestudieswefound20patientstobeenoughineachtreatmentgroup(studyIandIV).Inthepilotstudy,whereournewtreatmentmethod,US/CD-guidedarthroscopy,wasevaluatedwelimitedthenumberofpatients,sincewedidnotfinditethicallydefendabletooperateontoomanycases.Wedidnotknowifthetendonortheoperatedkneewouldreactnegativelyontheloadthatweallowedverysoonafterthesurgicalprocedure.InstudyI,thefollow-uptimediffersalotintermsofrange,mean14months

(range 2-35 months). Some of the patients, who only needed one injectiontreatment,wereveryearlybacktofulltendonloadingactivitywithoutpain.Theydidnotshowupforthefollow-ups,sincetheyweresatisfied.Theywereallofferedvisittimes,butwhencallingtodeclineavisittheyreportedviatelephonethattheywerepainless.

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S VIII


Conclusions

For clinical use, we recommend polidocanol 5mg/ml forUS-guided injectiontreatmentofchronicpainfulmidportionAchillestendinopathy,sincetherewasno difference in results when using polidocanol 10mg/ml. It is important tostrictlyfollowtheinitialmethoddescription.Smallvolumescanbeused.

Wefindthenewlyinventedsurgicalmethod,US/CD-guidedarthroscopicshaving,practical and reliable for treatment of proximal patellar tendinopathy (PT)/jumper´sknee(JK).Thereisabetterprecisionandlesstissuetraumacomparedtousingarthroscopicshavingalone.

ItseemsthatUS-guidedarthroscopicshavingoftheregionwithhighbloodflowandnervesonthedorsalsideofthetendon,canreducethetendonpainduringtendonloadingactivityandallowforamajorityofpatientswithPT/JKarelativelyquick(6-8weeks)returntopatellartendonloadingactivity.

Treatment with US/CD-guided sclerosing polidocanol injections and US/CD-guidedarthroscopicshavingshowgoodclinicalresultsfortreatmentofpatientswith PT/JK. Patients treatedwith arthroscopic shaving had a faster return toactivity,significantly lesspainandtheyweremoresatisfiedwiththetreatmentresult.

Ina longtermfollow-upbothmethodsshowedan improvementof thetendonstructureingreyscaleUS.AdecreasedbloodflowwasseenwithCD,intheregionwithtendonchanges.Therewasasignificantpainreductionduringactivitywithbothtreatments.InthegrouptreatedwithUS/CD-guidedsclerosing injectionsthe clinical results had improved to the same level as the early results in the arthroscopic shaving group. The only remaining difference between the twomethods concerned the anteroposterior (AP) thickness of the tendon. The APthicknesswas significantly reduced and the tendon structurewas improved intheUS-guidedarthroscopicshavinggroup,butnotinthegrouptreatedwithUS/CD-guidedsclerosinginjections.

Werecommendthenewlyinventedmethod,US/CD-guidedarthroscopicshavingmethodforpatientswithPT/JKbecauseitallowsforafastreturntosports,andit´spositiveeffectsontendonthicknessandstructureinthelongerperspective.

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Acknowledgements

This thesis was completed through a co-operation between the Capio Artro Clinic AB,StockholmSportsTraumaResearchCenter,KarolinskaInstitutet,StockholmandtheSportsMedicineUnitatUmeåUniversity,Umeå.Iwishtothankallofyouwhohavebeeninvolvedintheprocessofcompletingmywork.Therearesomepersons though I want to mention in particular:

Mysupervisor,professorHåkan Alfredson,youalwayssupportedtheideasandalwayscamewithnewones.Fearlessandcheerfulguidancethroughthediscoveryofanewterritory,andallyoursupportduringtheprocess!

Myassistant supervisor,Magnus Forssblad,MDPhD, thankyou foralwaystrustingmewhenwantingtotrynewapproachesinarthroscopyandfortakingthetimetositdowntotalkanddiscusswhenneeded.Givingmespace,freedom,supportandthetimetodothiswork.Thankyouboss!

Myassistantsupervisor,Martin Fahlström,MDPhD,thankyouforyourfirm,gentle, focusedand joyfulguidance through theworldof statisticsandwritingamongmanythings.Alwayslookingatmyworkfromanotherangle,leadingmythoughtsforward.Youare“myrock”!

My assistant supervisor, professor Suzanne Werner, thank you for alwayshavingsomethingpositivetosayandforcaringwhenthingshavebeenroughandbumpy.Youarealsotheonewhoistheexpertinfindingallthesmallmistakeswhenblindedtothemmyself.

Mywingmate,Kerstin Sunding,PhDstudentbiomed tech,without you thisthesis would not have been possible. You know it! All the time sharing yourknowledgeaboutultrasound,copingwithmycrazy ideas inaconstructivewayandall the luncheswith fruitfuldiscussions.My friend,bestof luckwithyourcomingthesisandIhopetobeabletobethereforyouasyouhavebeenforme,thankyouKerstin.

ProfessorEmeritus Ejnar Eriksson,whatcanIsay?YouaretheOne.Youhavetaught thedoctorswho then taughtmeall Iknowaboutarthroscopy.Withoutyou Iwouldnever have beenwhere I am today. Thank you for always caring,takingcareofmeatmeetingsandcoursesthroughtheyearsandforgivingmetheopportunitytopresentmywork.Youarelike“mygrandfather”andyouwillalwaysstayinmyheartandmind.


Maria Wiker,PTand Åsa Lönnqvist,PT,thankyouforallyourfriendlyandjoyful support and all the discussions about tendinopathy and rehabilitation.WithoutyouIwouldneverhavesomuchknowledgeaboutthe“rehabthinking”asIhavetoday.Youhavebeeninvaluabletome.

Lars Öhberg,MDPhD,co-authorandmentorinultrasound,alwayssocalmandpositive.Thankyouforallguidanceinthefieldofultrasound.

Sonia Johansson and Marianne Åström, OR nurses at Capio ArtroClinic,withoutyourpatienceandopenmindswhenIwantedtodoultrasoundsimultaneously with the arthroscopy I would never been able to complete my work.Thankyouforcheeringmeon,supportingmeandalwaysbeingsopositiveaboutdevelopingthisnewmethod.Youhelpedmetokeepmyfeetonthegroundduringtheprocess.

Many thanks toall thepresentand formerpersonnelatCapioArtroClinic forbelievinginmeandmakingmelaughwhenthingshavebeenstressful."A special thanks" to Dan Friberg, forpatientlymeasuringall theVASscalesandtakingphotographs.ToSusanne Johansson,forbookingallthepatientsand keeping my things organized and not the least taking the time whenever I haveneededtotalktoafriend.Ofcoursealsoawarmthankyou for thesupport Ihavegotten fromallofyoucolleguesattheCapioArtroClinic,no-onenamed–no-oneforgotten.

ToallpersonnelattheSportsMedicineUnitinUmeå,alwaystakingsogoodcareofmewhenIhavebeen“upnorth”,speciallyGunilla Solander,withoutyouIwould have been lost in space with all administrative work regarding courses and endlesspaperstofillin.

IwanttogivemyformercolleguesMats Caap, Jonas Sjögren och Michael Widmark inHallandcountya special thought forbeingmy friendsand ”youarealwaysinmymind”whenIamintheOR.WithoutyouIwouldneverhavebecomeanorthopedicsurgeonneitheranarthroscopist–thankyouforall thelaughs duringmy residency and for every Thursday when you putme in OR2“toget ridofme”withabunchofknees toscope.Heartfelt thoughtsalso toKarin GerdemarkattheHospitalinVarbergforalwaysbeingthereduringmyresidency,andImeanalways.

All the athletes and patients chosing to participate in my studies also need to be mentioned,thankyouforthetrustandpatience.

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Thomas Johansson and Anneli FalckatTMGStockholm,bothofyouneedtobementioned!Withoutyouthebookwouldneverhavebecomeasnice.

Mydearfriends,thankyouforhelpingmetofocusonwhatisimportantinlifeand not always having to think about work. For supporting me through therollercoasterthatlifesometimestendstobe.Theysaythereisareasonwhywehavetwoearsandonlyonemouth.TheartoflisteningandsupportingishardbutyouhavesucceededinthatartformandIfeelgratefultohavefriendslikeyou“girls”;Anna-Karin Frick, Anna Pappas, Josephine Halvorsen and Anna Lindberg-Steen.Youmakebaddayslessbadandgooddaysevenbetter.

Andatlastbutdefinitelynottheleast,myfamily;My sisters Cissi and Anna,forjustbeingmysisterswhoIlove.Despiteallourdifferenceswe always seem to find away to laughter. Through thick and thinsisters!

My dear mother Marie-Louice, thank you for being just the way you are, abit likePippiLongstocking, strongbut fragile, kind, supportive andallergic toinjustice. You have an enormous drive forward with strong ambitions and astrongtemper.Sometimestoomuchofaperfectionistthough,beingahindranceto yourself. Every single feature needed to go through the process of researchendingupwithathesis.IsupposeImighthavegottensomeofyourgenes.....Youarethebest,doneverchange.

MydearlatefatherUlf,allthewaythroughmylifeyouhavesupportedme.Totheendyoualwaysasked“howareYou”andyoualwayslistenedtotheanswer.Thankyouforteachingmetheimportanceofbeinghappy,followingthevoiceofmyheartandguidingme inthe importanceofreallyseeingthepeoplearoundme.Theimportanceofsometimesjusttakingabreak,breatheandnoticethelittlethings,awaveatsea,aflowerorjusttosmellthesaltybreeze,alltobeabletoperformattopwhenneeded.Momanddad–Iloveyou!IamgratefultohaveyouasmyparentsandIdedicatethisthesistoyou.

Tommy and Emil, you are the stars inmylife.Iloveyoutotheuniverseandback,thankyou forbeingmy joyand forbeingmylargestssupport.


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