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Systematic review| Volume 1, ISSUE 1, P10-15, January 2016

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Early ACL reconstruction in children leads to less meniscal and articular cartilage damage when compared with conservative or delayed treatment

      Background

      Anterior cruciate ligament (ACL) tears are being seen and treated with increasing frequency in children and adolescent athletes. The superiority of treating ACL tears in children and adolescents with acute reconstruction, delayed reconstruction or non-operative treatment remains controversial.

      Objectives

      To perform a systematic literature review to investigate for any associations between progressive intra-articular joint damage (increasing rates of meniscal and cartilage injury) with delayed or non-operative treatment of ACL tears in children and adolescents under age 18 when compared with acute ACL reconstruction (ACLR).

      Data sources

      PubMed, EMBASE and Cochrane computerised databases.

      Study eligibility criteria

      Inclusion criteria: (1) paediatric patient population (defined as <18 years of age), (2) investigated association between operative or non-operative treatment and consequent meniscal/chondral injury rates, (3) original research article, rather than a review, case report or meta-analysis. Exclusion criteria: (1) revision ACL cohort, (2) full-text article in a language other than English and (3) not a human clinical study.

      Participants

      Youth aged <18 years with ACL tears.

      Interventions

      Acute ACLR, delayed ACLR, non-operative management.

      Synthesis methods

      Qualitative synthesis.

      Results

      17 studies were included in the final analysis, all of which reported on medial meniscal injuries, of which 8 (47%) favoured acute reconstruction. 10 of 17 reported on cartilage injuries, of which 4 (40%) favoured acute ACLR. No study concluded that delayed reconstruction or non-operative management was associated with fewer cartilage or meniscus injuries.

      Limitations

      While the included studies provided patient age data, not all provided details about distribution of skeletal maturity. Furthermore, the majority of studies were retrospective and subject to selection bias, measurement bias and design bias (eg, surgical decision-making may have accounted for intra-articular pathology sustained at the time of injury). Constituent study heterogeneity with regard to ACLR techniques, definitions of surgical delay and variable length of follow-up precluded combining results in quantitative meta-analysis.

      Conclusions and implications of key findings

      On the basis of the available published literature which is largely retrospective, acute reconstruction for ACL tears appears to be associated with fewer medial meniscal injuries and articular cartilage lesions when compared with delayed or non-operative management. Several studies that were equivocal showed clinically relevant effect sizes but were underpowered to detect statistical differences between groups. Future prospective research in a large uniform cohort of skeletally immature patients with ACL tears may provide more answers to this important clinical question.

      Trial registration number

      CRD42015027614.

      Introduction

      Intrasubstance tears of the anterior cruciate ligament (ACL) were once considered a rare injury in children and adolescents; however, they are now observed with increasing frequency. This has been attributed to multiple factors including an increase in youth sports specialisation and competition, and increased awareness of ACL injuries in children. A recent epidemiological study revealed that the rate of ACL reconstruction (ACLR) in children under age 20 had increased nearly threefold over a 20-year period from 1990 to 2009, and indicated that adolescents and teenagers represent the largest per capita demographic of ACLRs.
      • Dodwell ER
      • Lamont LE
      • Green DW
      • et al.
      20 years of pediatric anterior cruciate ligament reconstruction in New York State.
      In light of the increasing frequency and awareness of ACL injuries in children, treatment strategies have evolved, catering to the unique anatomy of the skeletally immature patient. While non-operative or delayed surgical management until skeletal maturity was a historically ubiquitous treatment for complete ACL rupture due to the risk of physeal damage inherent to surgical treatment,
      • Woods GW
      • O'Connor DP
      Delayed anterior cruciate ligament reconstruction in adolescents with open physes.
      newer surgical techniques and instrumentation have expanded the options for acute physeal-respecting ACLR and there are many techniques with an acceptable safety profile for patients with growth remaining.
      • Lawrence JTR
      • Bowers AL
      • Belding J
      • et al.
      All-epiphyseal anterior cruciate ligament reconstruction in skeletally immature patients.
      ,
      • Anderson AF
      Transepiphyseal replacement of the anterior cruciate ligament in skeletally immature patients. A preliminary report.
      ,
      • Kocher MS
      • Garg S
      • Micheli LJ
      Physeal sparing reconstruction of the anterior cruciate ligament in skeletally immature prepubescent children and adolescents.
      ,
      • McCarthy MM
      • Graziano J
      • Green DW
      • et al.
      All-epiphyseal, all-inside anterior cruciate ligament reconstruction technique for skeletally immature patients.
      ,
      • Micheli LJ
      • Rask B
      • Gerberg L
      Anterior cruciate ligament reconstruction in patients who are prepubescent.
      ,
      • Gausden EB
      • Calcei JG
      • Fabricant PD
      • et al.
      Surgical options for anterior cruciate ligament reconstruction in the young child.
      ,
      • Fabricant PD
      • Jones KJ
      • Delos D
      • et al.
      Reconstruction of the anterior cruciate ligament in the skeletally immature athlete: a review of current concepts: AAOS exhibit selection.
      ,
      • Kocher MS
      • Smith JT
      • Zoric BJ
      • et al.
      Transphyseal anterior cruciate ligament reconstruction in skeletally immature pubescent adolescents.
      The superiority of treating ACL tears in children and adolescents with acute reconstruction, delayed reconstruction or non-operative treatment remains controversial in the orthopaedic literature.
      • Reider B
      It takes more than timing: response.
      ,
      • Reider B
      A matter of timing.
      ,
      • Moksnes H
      • Engebretsen L
      It takes more than timing: letter to the editor.
      The potential for increased risk of further irreparable cartilage and/or meniscal damage in the unreconstructed knee is germane to the arguments for and against acute reconstruction in children and adolescents.
      • Funahashi KM
      • Moksnes H
      • Maletis GB
      • et al.
      Anterior cruciate ligament injuries in adolescents with open physis: effect of recurrent injury and surgical delay on meniscal and cartilage injuries.
      This is of particular concern in patients who do not modify their postinjury activity levels, as is often the case in active children and adolescents.
      While recent quantitative synthesis of the available literature has been performed evaluating recurrent instability, pathological laxity and return to activity,
      • Ramski DE
      • Kanj WW
      • Franklin CC
      • et al.
      Anterior cruciate ligament tears in children and adolescents: a meta-analysis of nonoperative versus operative treatment.
      no such study has been performed evaluating the effect of surgical delay on further intra-articular damage. The purpose of this study was therefore to perform a systematic review of the orthopaedic surgery literature to investigate for any associations between progressive intra-articular joint damage (increasing rates of cartilage and meniscal injury) with delayed or non-operative treatment of ACL tears in children and adolescents under age 18 when compared with acute ACLR. We hypothesised that those patients who underwent initial non-operative management or experienced a surgical delay would have a greater risk of cartilage and meniscal injury than those who underwent acute ACLR.

      Methods

      Study design and search strategy

      The current study was registered with the International Prospective Register of Systematic Reviews (PROSPERO), registration number CRD42015027614. A systematic review was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines.
      • Moher D
      • Liberati A
      • Tetzlaff J
      • PRISMA Group
      • et al.
      Preferred Reporting Items for Systematic Reviews and Meta-Analyses: the PRISMA statement.
      An electronic search of the PubMed, EMBASE and Cochrane computerised databases was conducted by two independent reviewers (NL and ES) on 8 June 2015. The final sequence of the employed search terms is as follows: (‘ACL’ OR 'Anterior Cruciate Ligament') AND ('delay' OR ‘conservative’ OR 'non-operative') AND ('pediatric' OR ‘adolescent’ OR ‘physes’ OR ‘physis’ OR 'immature') AND ('cartilage' OR ‘meniscus’ OR ‘meniscal’ OR ‘chondral‘). A complete search strategy and results are presented in table 1. A filter was utilised in order to limit the search to studies that were published after 1 January 2000. The references of each unique full-text article were subsequently examined in order to identify additional articles that could potentially be relevant to the study. Since this study uses the existing literature and does not involve human subjects, Institutional Review Board (IRB) approval was not required.
      Table 1Search terms utilised in the systematic review
      Search termsReference databaseNumber of identified studies
      (1) ‘ACL’ OR ‘Anterior Cruciate Ligament‘PubMed12 298
      EMBASE15 741
      Cochrane1212
      (2) #1 AND (‘delay’ OR ‘conservative’ OR ‘nonoperative‘)PubMed360
      EMBASE612
      Cochrane52
      (3) #2 AND (‘pediatric’ OR ‘adolescent’ OR ‘physes’ OR ‘physis’ OR ‘immature‘)PubMed117
      EMBASE151
      Cochrane10
      (4) #3 AND (‘cartilage’ OR ‘meniscus’ OR ‘meniscal’ OR ‘chondral‘)PubMed54
      EMBASE75
      Cochrane5
      Search performed on 8 June 2015. Search limited to articles published on or after 1 January 2000.

      Study selection

      The titles and abstract sections of each of the unique studies identified via the electronic database and bibliography searches were then examined for relevance to the study question. A full-text review was subsequently performed for potentially relevant studies and final inclusion was determined on the basis of the following criteria: (1) paediatric patient population (defined as <18 years of age), (2) investigated association between operative or non-operative treatment and consequent meniscal/chondral injury rates and (3) original research article, rather than a review, case report or meta-analysis. Exclusion criteria included: (1) revision ACL cohort, (2) full-text article in a language other than English and (3) not a human clinical study.

      Data extraction

      Three authors (PDF, NL and AIC) independently extracted data from each of the studies that met the established inclusion/exclusion criteria, with discrepancies resolved unanimously through discussion of each included study. General information including the name of the first author, journal, year of publication, level of evidence and intervention was collected for each investigation. When available, the definition for delayed treatment, average follow-up time, and incidence of medial meniscal injury and cartilage lesions along with the corresponding comparative analyses and p values were recorded. Post hoc analyses were performed from original tabular study data, when possible, using χ2 and Fisher's exact tests as appropriate. A full list of the included articles along with the corresponding data is depicted in table 2.
      Table 2Characteristics of studies comparing ACLR with non-operative treatment
      AuthorNJournalLOEDelayed treatment definition (weeks)Intervention technique(s)Follow-up (months)Medial meniscal damage†Chondral injuriesNotes
      Acute (%)Delayed or non-operative (%)p ValueAcute (%)Delayed or non-operative (%)p Value
      Newman et al
      • Newman JT
      • Carry PM
      • Terhune EB
      • et al.
      Factors predictive of concomitant injuries among children and adolescents undergoing anterior cruciate ligament surgery.
      272AJSMIII12Unspecified ACLR techniques1212.344.40.001*10.348.10.002*Post hoc χ2 analysis performed to generate p values. Included patients represent a subcohort of patients under 14 years of age
      Anderson et al
      • Anderson AF
      • Anderson CN
      Correlation of meniscal and articular cartilage injuries in children and adolescents with timing of anterior cruciate ligament reconstruction.
      135AJSMIII12AE

      TP
      24500.007*7280.005*
      Funahashi et al
      • Funahashi KM
      • Moksnes H
      • Maletis GB
      • et al.
      Anterior cruciate ligament injuries in adolescents with open physis: effect of recurrent injury and surgical delay on meniscal and cartilage injuries.
      71AJSMIII52 and 104Unspecified ACLR18NRNR0.11NRNR0.5327.7% of the general operative cohort had documented medial meniscal injuries

      57.4% presented with chondral injury. (Study gave p values but no point estimate or distributional data)
      Guenther et al
      • Guenther ZD
      • Swami V
      • Dhillon SS
      • et al.
      Meniscal injury after adolescent anterior cruciate ligament injury: how long are patients at risk?.
      112CORRIV52Unspecified ACLR1120510.001*Follow-up is the time from injury to surgery (meniscal tears diagnosed at arthroscopy)
      Lawrence et al
      • Lawrence JTR
      • Argawal N
      • Ganley TJ
      Degeneration of the knee joint in skeletally immature patients with a diagnosis of an anterior cruciate ligament tear: is there harm in delay of treatment?.
      70AJSMIII12AE1215450.011*10450.001*Reported chondral injuries were all in the lateral compartment
      Streich et al
      • Streich NA
      • Barié A
      • Gotterbarm T
      • et al.
      Transphyseal reconstruction of the anterior cruciate ligament in prepubescent athletes.
      28KSSTAIIIn/aNon-operative vs TP7031.333.3>0.99Meniscal injury rates calculated from tabular data, post hoc Fisher's exact test performed to generate p value for meniscal injury. Operative group mean time to surgery 84 weeks
      Millett et al
      • Millett PJ
      • Willis AA
      • Warren RF
      Associated injuries in pediatric and adolescent anterior cruciate ligament tears: does a delay in treatment increase the risk of meniscal tear?.
      39ArthroscopyIII6Various techniques‡1511360.022*
      Moksnes et al
      • Moksnes H
      • Engebretsen L
      • Risberg MA
      Prevalence and incidence of new meniscus and cartilage injuries after a nonoperative treatment algorithm for ACL tears in skeletally immature children: a prospective MRI study.
      40AJSIVn/aNon-operative only4628.57.1Time from injury to final MRI follow-up

      19.5% eventually required surgery for meniscus injuries

      32% eventually required ACLR
      Woods et al
      • Woods GW
      • O'Connor DP
      Delayed anterior cruciate ligament reconstruction in adolescents with open physes.
      129AJSMIII26TP8.730.8>0.056.811.5>0.05Those with open physes were delayed until skeletal maturity
      Aichroth et al
      • Aichroth PM
      • Patel DV
      • Zorrilla P
      The natural history and treatment of rupture of the anterior cruciate ligament in children and adolescents. A prospective review.
      60BJJIIIn/aNon-operative vs TP4919.134.80.2612.813>0.99Meniscal injury rates calculated from tabular data; post hoc χ2 analyses performed to generate p values for cartilage and meniscal injuries

      3 of the 8 (37.5%) meniscal tears in the non-operative group required surgical treatment in the observation period
      Henry et al
      • Henry J
      • Chotel F
      • Chouteau J
      • et al.
      Rupture of the anterior cruciate ligament in children: early reconstruction with open physes or delayed reconstruction to skeletal maturity?.
      56KSSTAIIIn/aPTP

      TP
      2710.340.70.01*
      McIntosh et al
      • McIntosh AL
      • Dahm DL
      • Stuart MJ
      Anterior cruciate ligament reconstruction in the skeletally immature patient.
      16ArthroscopyIVn/aTP2425New meniscal injury diagnosed at a mean of 6.9 weeks after injury
      Gebhard et al
      • Gebhard F
      • Ellermann A
      • Hoffmann F
      • et al.
      Multicenter-study of operative treatment of intraligamentous tears of the anterior cruciate ligament in children and adolescents: comparison of four different techniques.
      68KSSTAIV8ITB

      TP
      3215.630.60.25Meniscal injury rates calculated from tabular data. Post hoc χ2 analysis performed to generate p value for meniscal injuries
      Cohen et al
      • Cohen M
      • Ferretti M
      • Quarteiro M
      • et al.
      Transphyseal anterior cruciate ligament reconstruction in patients with open physes.
      26ArthroscopyIV24TP4521.171.40.028*5.328.60.167Meniscal injury rates calculated from tabular data. Post hoc Fisher's exact tests performed to generate p values for cartilage and meniscal injuries. 1 (14%) patient in the delayed group had a lateral meniscal tear
      Calvo et al
      • Calvo R
      • Figueroa D
      • Gili F
      • et al.
      Transphyseal anterior cruciate ligament reconstruction in patients with open physes: 10-year follow-up study.
      27AJSMIV24TP1272571.40.065Meniscal injury rates calculated from tabular data. Post hoc Fisher's exact test performed to generate p value for meniscal injuries. No differentiation was made between lateral and medial menisci. 2 (7.4%) patients sustained chondral injury, but surgical timing was NR
      Dumont et al
      • Dumont GD
      • Hogue GD
      • Padalecki JR
      • et al.
      Meniscal and chondral injuries associated with pediatric anterior cruciate ligament tears: relationship of treatment time and patient-specific factors.
      370AJSMIII21.4ITB

      AE
      Mean NR37.853.50.014*52.776.7<0.001*Although the journal characterised this study as representing level III evidence, the investigation was a retrospective chart review. Lateral meniscus tears reported as well: early vs delayed (56.0% vs 57.4%). Post hoc χ2 analysis used to generate p value for cartilage injuries
      Ralles et al
      • Ralles S
      • Agel J
      • Obermeier M
      • et al.
      Incidence of secondary intra-articular injuries with time to anterior cruciate ligament reconstruction.
      252AJSMIII12TP

      PTP

      AE
      2.627.436.40.3922.33.00.573Subcohort data obtained from study authors. Time to follow-up equals mean time to surgery for the cohort. Post hoc χ2/Fisher's exact analyses performed to generate p values. Authors reported time to surgery cut-offs of 12 and 52 weeks in the original article
      *p<0.05.
      †All studies examined the risk of medial meniscal tears; few examined lateral meniscal tears, and no investigation reported a statistically significant correlation between operative delay and risk of lateral meniscal injury.
      ‡Various Techniques included: primary repair, primary repair with hamstring augmentation (autograft and allograft), ACLR with hamstring autograft, ACLR with BTB autograft. Both open and arthroscopically assisted techniques were used.
      ACL, anterior cruciate ligament; ACLR, ACL reconstruction; AE, all-epiphyseal ACLR; BTB, bone-patellar tendon-bone; ITB, iliotibial band extra-articular and intra-articular reconstruction; LOE, level of evidence; n/a, not applicable; NR, not reported; PTP, partial transphyseal (hybrid) ACLR (all-epiphyseal femur, transphyseal tibia); TP, transphyseal ACLR.

      Results

      Study inclusion

      The original electronic database search yielded 91 unique articles, 7 of which were identified via a manual search of the references of those identified through electronic database search. Twenty-eight of these were deemed to be not relevant to the research topic based on title and abstract review, resulting in 63 full-text articles being assessed for inclusion/exclusion criteria. A total of 46 studies were excluded because they were: not examining outcome variables of interest (N=18), adult-focused (N=13), review articles (N=12), not clinical studies (N=2) or case reports (N=1). Seventeen studies were included in the final qualitative synthesis, as demonstrated in the PRISMA flow diagram (figure 1).
      Figure thumbnail gr1
      Figure 1Preferred reporting items for systematic reviews and meta-analyses flow diagram.

      General study characteristics

      Of the 17 included studies, 14 involved solely surgical reconstruction of the torn ACL while 3 incorporated non-operative treatment cohorts. Out of the investigations that included non-operative groups, two
      • Streich NA
      • Barié A
      • Gotterbarm T
      • et al.
      Transphyseal reconstruction of the anterior cruciate ligament in prepubescent athletes.
      • Aichroth PM
      • Patel DV
      • Zorrilla P
      The natural history and treatment of rupture of the anterior cruciate ligament in children and adolescents. A prospective review.
      compared operative and non-operative approaches in the context of concomitant injury while one
      • Moksnes H
      • Engebretsen L
      • Risberg MA
      Prevalence and incidence of new meniscus and cartilage injuries after a nonoperative treatment algorithm for ACL tears in skeletally immature children: a prospective MRI study.
      assessed the outcomes of conservative treatment alone. One of the studies that evaluated operative versus non-operative treatment provided the rates of both meniscal and chondral injury
      • Aichroth PM
      • Patel DV
      • Zorrilla P
      The natural history and treatment of rupture of the anterior cruciate ligament in children and adolescents. A prospective review.
      while the second only reported the incidence of medial meniscal damage for the two groups.
      • Streich NA
      • Barié A
      • Gotterbarm T
      • et al.
      Transphyseal reconstruction of the anterior cruciate ligament in prepubescent athletes.
      Out of the studies comparing acute and delayed operative treatment, eight
      • Woods GW
      • O'Connor DP
      Delayed anterior cruciate ligament reconstruction in adolescents with open physes.
      • Funahashi KM
      • Moksnes H
      • Maletis GB
      • et al.
      Anterior cruciate ligament injuries in adolescents with open physis: effect of recurrent injury and surgical delay on meniscal and cartilage injuries.
      • Newman JT
      • Carry PM
      • Terhune EB
      • et al.
      Factors predictive of concomitant injuries among children and adolescents undergoing anterior cruciate ligament surgery.
      ,
      • Anderson AF
      • Anderson CN
      Correlation of meniscal and articular cartilage injuries in children and adolescents with timing of anterior cruciate ligament reconstruction.
      ,
      • Lawrence JTR
      • Argawal N
      • Ganley TJ
      Degeneration of the knee joint in skeletally immature patients with a diagnosis of an anterior cruciate ligament tear: is there harm in delay of treatment?.
      ,
      • Cohen M
      • Ferretti M
      • Quarteiro M
      • et al.
      Transphyseal anterior cruciate ligament reconstruction in patients with open physes.
      ,
      • Dumont GD
      • Hogue GD
      • Padalecki JR
      • et al.
      Meniscal and chondral injuries associated with pediatric anterior cruciate ligament tears: relationship of treatment time and patient-specific factors.
      ,
      • Ralles S
      • Agel J
      • Obermeier M
      • et al.
      Incidence of secondary intra-articular injuries with time to anterior cruciate ligament reconstruction.
      included data for both meniscal and chondral injury while six
      • Guenther ZD
      • Swami V
      • Dhillon SS
      • et al.
      Meniscal injury after adolescent anterior cruciate ligament injury: how long are patients at risk?.
      ,
      • Millett PJ
      • Willis AA
      • Warren RF
      Associated injuries in pediatric and adolescent anterior cruciate ligament tears: does a delay in treatment increase the risk of meniscal tear?.
      ,
      • Henry J
      • Chotel F
      • Chouteau J
      • et al.
      Rupture of the anterior cruciate ligament in children: early reconstruction with open physes or delayed reconstruction to skeletal maturity?.
      ,
      • McIntosh AL
      • Dahm DL
      • Stuart MJ
      Anterior cruciate ligament reconstruction in the skeletally immature patient.
      ,
      • Gebhard F
      • Ellermann A
      • Hoffmann F
      • et al.
      Multicenter-study of operative treatment of intraligamentous tears of the anterior cruciate ligament in children and adolescents: comparison of four different techniques.
      ,
      • Calvo R
      • Figueroa D
      • Gili F
      • et al.
      Transphyseal anterior cruciate ligament reconstruction in patients with open physes: 10-year follow-up study.
      only reported information regarding medial meniscal damage. All studies reporting meniscal injury data examined the risk of medial meniscal tears while few examined lateral meniscal tears. Furthermore, since medial meniscal tears represent the majority of repetitive traumatic tears noted in unstable knees while lateral meniscal tears occur more commonly in the acute setting,
      • Lawrence JTR
      • Argawal N
      • Ganley TJ
      Degeneration of the knee joint in skeletally immature patients with a diagnosis of an anterior cruciate ligament tear: is there harm in delay of treatment?.
      medial meniscal injuries were investigated for this study. This analysis included 6
      • Moksnes H
      • Engebretsen L
      • Risberg MA
      Prevalence and incidence of new meniscus and cartilage injuries after a nonoperative treatment algorithm for ACL tears in skeletally immature children: a prospective MRI study.
      • Cohen M
      • Ferretti M
      • Quarteiro M
      • et al.
      Transphyseal anterior cruciate ligament reconstruction in patients with open physes.
      • Guenther ZD
      • Swami V
      • Dhillon SS
      • et al.
      Meniscal injury after adolescent anterior cruciate ligament injury: how long are patients at risk?.
      • McIntosh AL
      • Dahm DL
      • Stuart MJ
      Anterior cruciate ligament reconstruction in the skeletally immature patient.
      ,
      • Gebhard F
      • Ellermann A
      • Hoffmann F
      • et al.
      Multicenter-study of operative treatment of intraligamentous tears of the anterior cruciate ligament in children and adolescents: comparison of four different techniques.
      ,
      • Calvo R
      • Figueroa D
      • Gili F
      • et al.
      Transphyseal anterior cruciate ligament reconstruction in patients with open physes: 10-year follow-up study.
      studies of level IV evidence and 11
      • Woods GW
      • O'Connor DP
      Delayed anterior cruciate ligament reconstruction in adolescents with open physes.
      • Funahashi KM
      • Moksnes H
      • Maletis GB
      • et al.
      Anterior cruciate ligament injuries in adolescents with open physis: effect of recurrent injury and surgical delay on meniscal and cartilage injuries.
      • Streich NA
      • Barié A
      • Gotterbarm T
      • et al.
      Transphyseal reconstruction of the anterior cruciate ligament in prepubescent athletes.
      • Aichroth PM
      • Patel DV
      • Zorrilla P
      The natural history and treatment of rupture of the anterior cruciate ligament in children and adolescents. A prospective review.
      • Newman JT
      • Carry PM
      • Terhune EB
      • et al.
      Factors predictive of concomitant injuries among children and adolescents undergoing anterior cruciate ligament surgery.
      ,
      • Anderson AF
      • Anderson CN
      Correlation of meniscal and articular cartilage injuries in children and adolescents with timing of anterior cruciate ligament reconstruction.
      ,
      • Lawrence JTR
      • Argawal N
      • Ganley TJ
      Degeneration of the knee joint in skeletally immature patients with a diagnosis of an anterior cruciate ligament tear: is there harm in delay of treatment?.
      • Dumont GD
      • Hogue GD
      • Padalecki JR
      • et al.
      Meniscal and chondral injuries associated with pediatric anterior cruciate ligament tears: relationship of treatment time and patient-specific factors.
      • Ralles S
      • Agel J
      • Obermeier M
      • et al.
      Incidence of secondary intra-articular injuries with time to anterior cruciate ligament reconstruction.
      • Millett PJ
      • Willis AA
      • Warren RF
      Associated injuries in pediatric and adolescent anterior cruciate ligament tears: does a delay in treatment increase the risk of meniscal tear?.
      • Henry J
      • Chotel F
      • Chouteau J
      • et al.
      Rupture of the anterior cruciate ligament in children: early reconstruction with open physes or delayed reconstruction to skeletal maturity?.
      of level III evidence. Studies included in the final analysis along with corresponding characteristics and their comparative analyses are presented in table 2.

      Delayed versus acute ACLR

      A total of 14 studies examined the rates of concomitant injury following acute or delayed ACLR in children. Of these, five studies demonstrated a statistically significant (p<0.05) association between delayed ACLR and the presence of new meniscal or chondral injuries at the time of surgery.
      • Funahashi KM
      • Moksnes H
      • Maletis GB
      • et al.
      Anterior cruciate ligament injuries in adolescents with open physis: effect of recurrent injury and surgical delay on meniscal and cartilage injuries.
      • Newman JT
      • Carry PM
      • Terhune EB
      • et al.
      Factors predictive of concomitant injuries among children and adolescents undergoing anterior cruciate ligament surgery.
      ,
      • Anderson AF
      • Anderson CN
      Correlation of meniscal and articular cartilage injuries in children and adolescents with timing of anterior cruciate ligament reconstruction.
      ,
      • Lawrence JTR
      • Argawal N
      • Ganley TJ
      Degeneration of the knee joint in skeletally immature patients with a diagnosis of an anterior cruciate ligament tear: is there harm in delay of treatment?.
      • Dumont GD
      • Hogue GD
      • Padalecki JR
      • et al.
      Meniscal and chondral injuries associated with pediatric anterior cruciate ligament tears: relationship of treatment time and patient-specific factors.
      A large investigation performed by Dumont et al,
      • Dumont GD
      • Hogue GD
      • Padalecki JR
      • et al.
      Meniscal and chondral injuries associated with pediatric anterior cruciate ligament tears: relationship of treatment time and patient-specific factors.
      which defined a treatment delay to be 21.4 weeks from the onset of injury, reported that 53.5% of children in the delayed cohort sustained medial meniscal injuries, compared with 37.8% of those treated acutely (p=0.014). Likewise, 76.7% of paediatric patients treated after 21.4 weeks presented with cartilage injuries, compared with 52.7% of their counterparts receiving acute reconstruction (p<0.001). However, two large studies reported no differences in the rates of chondral or medial meniscal injuries between patients treated acutely or with a delay.
      • Woods GW
      • O'Connor DP
      Delayed anterior cruciate ligament reconstruction in adolescents with open physes.
      • Ralles S
      • Agel J
      • Obermeier M
      • et al.
      Incidence of secondary intra-articular injuries with time to anterior cruciate ligament reconstruction.
      One of these investigations considered a delay to be 12 weeks following the initial injury while the second used 26 weeks as the definition for delay. The rest of the studies examining the outcomes of surgically treated ACL tears, which reported data regarding only meniscal damage, demonstrated that children who experience a delay to treatment develop medial meniscal injuries at significantly greater rates than those treated acutely (p<0.05).
      • Guenther ZD
      • Swami V
      • Dhillon SS
      • et al.
      Meniscal injury after adolescent anterior cruciate ligament injury: how long are patients at risk?.
      ,
      • Millett PJ
      • Willis AA
      • Warren RF
      Associated injuries in pediatric and adolescent anterior cruciate ligament tears: does a delay in treatment increase the risk of meniscal tear?.
      ,
      • Henry J
      • Chotel F
      • Chouteau J
      • et al.
      Rupture of the anterior cruciate ligament in children: early reconstruction with open physes or delayed reconstruction to skeletal maturity?.

      Operative versus non-operative treatment

      Only two studies directly compared children whose ACL tears were treated via operative reconstruction with those who received conservative treatment. Streich et al
      • Streich NA
      • Barié A
      • Gotterbarm T
      • et al.
      Transphyseal reconstruction of the anterior cruciate ligament in prepubescent athletes.
      retrospectively compared the outcomes of 16 paediatric patients who underwent transphyseal ACLR with 12 who were treated non-operatively. The authors reported rates of medial meniscal injury to be 31.3% and 33.3% (p>0.99; post hoc Fisher's exact test) for the operative and non-operative cohorts, respectively. Similarly, Aichroth et al
      • Aichroth PM
      • Patel DV
      • Zorrilla P
      The natural history and treatment of rupture of the anterior cruciate ligament in children and adolescents. A prospective review.
      examined post-treatment differences between 47 children who underwent transphyseal reconstruction and 23 who received non-operative treatment. Calculations from the authors' tabular data demonstrated medial meniscal injury rates to be 19.1% and 34.8% for the reconstruction and non-operative groups, respectively. While this difference appears to be clinically relevant, the study was most likely underpowered to detect a statistically significant difference between the two groups (p=0.26; post hoc χ2 analysis). The Aichroth et al
      • Aichroth PM
      • Patel DV
      • Zorrilla P
      The natural history and treatment of rupture of the anterior cruciate ligament in children and adolescents. A prospective review.
      study noted similar rates of cartilage injury between groups (p>0.99; post hoc χ2 analysis).

      Non-operative treatment

      One study examined the rates of meniscal and chondral injuries for patients whose ACL tears were treated non-operatively. Moksnes et al
      • Moksnes H
      • Engebretsen L
      • Risberg MA
      Prevalence and incidence of new meniscus and cartilage injuries after a nonoperative treatment algorithm for ACL tears in skeletally immature children: a prospective MRI study.
      prospectively evaluated children with ACL tears who received non-operative therapy. The authors reported 28.5% of their conservatively treated patients developing medial meniscal damage and 7.1% sustaining a cartilage injury, suggesting that these injury rates are similar to those of other studies in which patients received operative treatment. However, 19.5% of their initial non-operative cohort sustained new meniscal pathology requiring surgery and 32% necessitated subsequent ACLR for symptomatic instability.

      Discussion

      The superiority of treating ACL tears in children and adolescents with acute reconstruction, delayed reconstruction or non-operative treatment remains controversial in the orthopaedic literature.
      • Reider B
      It takes more than timing: response.
      ,
      • Reider B
      A matter of timing.
      ,
      • Moksnes H
      • Engebretsen L
      It takes more than timing: letter to the editor.
      While some authors secondarily reported a possible effect between surgical delay and cartilage and meniscus damage in clinical reports investigating other primary outcomes, Millett et al
      • Millett PJ
      • Willis AA
      • Warren RF
      Associated injuries in pediatric and adolescent anterior cruciate ligament tears: does a delay in treatment increase the risk of meniscal tear?.
      and subsequently Lawrence et al
      • Lawrence JTR
      • Argawal N
      • Ganley TJ
      Degeneration of the knee joint in skeletally immature patients with a diagnosis of an anterior cruciate ligament tear: is there harm in delay of treatment?.
      directly investigated the association between delayed ACLR and irreparable intra-articular joint damage in youth athletes. Subsequently, several studies have been performed to further investigate this topic.
      • Funahashi KM
      • Moksnes H
      • Maletis GB
      • et al.
      Anterior cruciate ligament injuries in adolescents with open physis: effect of recurrent injury and surgical delay on meniscal and cartilage injuries.
      • Moksnes H
      • Engebretsen L
      • Risberg MA
      Prevalence and incidence of new meniscus and cartilage injuries after a nonoperative treatment algorithm for ACL tears in skeletally immature children: a prospective MRI study.
      ,
      • Newman JT
      • Carry PM
      • Terhune EB
      • et al.
      Factors predictive of concomitant injuries among children and adolescents undergoing anterior cruciate ligament surgery.
      ,
      • Anderson AF
      • Anderson CN
      Correlation of meniscal and articular cartilage injuries in children and adolescents with timing of anterior cruciate ligament reconstruction.
      • Dumont GD
      • Hogue GD
      • Padalecki JR
      • et al.
      Meniscal and chondral injuries associated with pediatric anterior cruciate ligament tears: relationship of treatment time and patient-specific factors.
      ,
      • Ralles S
      • Agel J
      • Obermeier M
      • et al.
      Incidence of secondary intra-articular injuries with time to anterior cruciate ligament reconstruction.
      ,
      • Guenther ZD
      • Swami V
      • Dhillon SS
      • et al.
      Meniscal injury after adolescent anterior cruciate ligament injury: how long are patients at risk?.
      • Calvo R
      • Figueroa D
      • Gili F
      • et al.
      Transphyseal anterior cruciate ligament reconstruction in patients with open physes: 10-year follow-up study.
      The large majority of studies support the notion of acute treatment of ACL tears in children and adolescents given the noted associations between delay or non-operative management and cartilage
      • Newman JT
      • Carry PM
      • Terhune EB
      • et al.
      Factors predictive of concomitant injuries among children and adolescents undergoing anterior cruciate ligament surgery.
      ,
      • Anderson AF
      • Anderson CN
      Correlation of meniscal and articular cartilage injuries in children and adolescents with timing of anterior cruciate ligament reconstruction.
      ,
      • Lawrence JTR
      • Argawal N
      • Ganley TJ
      Degeneration of the knee joint in skeletally immature patients with a diagnosis of an anterior cruciate ligament tear: is there harm in delay of treatment?.
      • Dumont GD
      • Hogue GD
      • Padalecki JR
      • et al.
      Meniscal and chondral injuries associated with pediatric anterior cruciate ligament tears: relationship of treatment time and patient-specific factors.
      or meniscal
      • Newman JT
      • Carry PM
      • Terhune EB
      • et al.
      Factors predictive of concomitant injuries among children and adolescents undergoing anterior cruciate ligament surgery.
      ,
      • Anderson AF
      • Anderson CN
      Correlation of meniscal and articular cartilage injuries in children and adolescents with timing of anterior cruciate ligament reconstruction.
      ,
      • Lawrence JTR
      • Argawal N
      • Ganley TJ
      Degeneration of the knee joint in skeletally immature patients with a diagnosis of an anterior cruciate ligament tear: is there harm in delay of treatment?.
      ,
      • Cohen M
      • Ferretti M
      • Quarteiro M
      • et al.
      Transphyseal anterior cruciate ligament reconstruction in patients with open physes.
      ,
      • Dumont GD
      • Hogue GD
      • Padalecki JR
      • et al.
      Meniscal and chondral injuries associated with pediatric anterior cruciate ligament tears: relationship of treatment time and patient-specific factors.
      • Guenther ZD
      • Swami V
      • Dhillon SS
      • et al.
      Meniscal injury after adolescent anterior cruciate ligament injury: how long are patients at risk?.
      ,
      • Millett PJ
      • Willis AA
      • Warren RF
      Associated injuries in pediatric and adolescent anterior cruciate ligament tears: does a delay in treatment increase the risk of meniscal tear?.
      ,
      • Henry J
      • Chotel F
      • Chouteau J
      • et al.
      Rupture of the anterior cruciate ligament in children: early reconstruction with open physes or delayed reconstruction to skeletal maturity?.
      pathology.
      Of the 17 studies included in this review, all reported on medial meniscal injuries, of which 8 (47%) favoured acute ACLR. Ten of the 17 reported on cartilage injuries, of which 4 (40%) favoured acute reconstruction. For meniscal and cartilage injuries, those that did not favour acute treatment either showed no difference in outcomes or did not provide comparisons between groups. Despite the lack of study homogeneity and thus the inability to calculate weighted summary statistics in meta-analysis, these summary data seem to favour acute reconstruction of ACL injuries in patients aged under 18 years, as this was associated with a lower incidence of medial meniscal injury and global cartilage lesions.
      One study strongly advocated a trial of non-operative management in skeletally immature children with ACL tears.
      • Moksnes H
      • Engebretsen L
      • Risberg MA
      Prevalence and incidence of new meniscus and cartilage injuries after a nonoperative treatment algorithm for ACL tears in skeletally immature children: a prospective MRI study.
      It rigorously evaluated 40 skeletally immature patients with longitudinal MRI scans in order to determine new intra-articular pathology, and concluded that the risk of subsequent pathology was low. However, arthroscopy remains the gold standard for intra-articular evaluation, and MRI may be subject to false-negative reporting. In fact, non-contrast MRI techniques have been recently reported to have variable sensitivity, some as low as 42% for cartilage lesions and 62–78% for meniscus lesions, indicating that an MRI study of intra-articular pathology may underestimate the prevalence of disease through false-negative reporting.
      • Nikolaou VS
      • Chronopoulos E
      • Savvidou C
      • et al.
      MRI efficacy in diagnosing internal lesions of the knee: a retrospective analysis.
      • Magee T
      Accuracy of 3-Tesla MR and MR arthrography in diagnosis of meniscal retear in the post-operative knee.
      Furthermore, the clinical outcomes reported in the Moksnes et al
      • Moksnes H
      • Engebretsen L
      • Risberg MA
      Prevalence and incidence of new meniscus and cartilage injuries after a nonoperative treatment algorithm for ACL tears in skeletally immature children: a prospective MRI study.
      study revealed that during the 4 years postinjury, one in three required ACLR for persistent instability and one in five required arthroscopy for newly sustained meniscal pathology. While this may suggest that universally performing ACL reconstructions in active skeletally immature patients may subject some to unnecessary surgery, it is up to treating surgeons and their patients and families to weigh the risks and benefits of acute ACLR versus controlled rehabilitation, understanding the significant risk of developing irreparable meniscal and/or chondral pathology as well as prolonged activity reduction due to a period of rehabilitation. Patients and families should also be aware that in one-third of patients initially treated non-operatively, surgery for persistent instability despite controlled rehabilitation may be necessary.
      It is important to note the limitations inherent to this systematic review and its included investigations. First, the heterogeneity of ACLR techniques, definitions of surgical delay and variable length of follow-up precluded quantitative meta-analysis of the included studies. This is unfortunate because meta-analysis is able to combine similar study cohorts in order to gain statistical power and draw conclusions that may not have existed previously. Several studies evaluated in this review indicated statistical equivalence between surgical delay or non-operative treatment and intra-articular pathology,
      • Woods GW
      • O'Connor DP
      Delayed anterior cruciate ligament reconstruction in adolescents with open physes.
      • Funahashi KM
      • Moksnes H
      • Maletis GB
      • et al.
      Anterior cruciate ligament injuries in adolescents with open physis: effect of recurrent injury and surgical delay on meniscal and cartilage injuries.
      • Streich NA
      • Barié A
      • Gotterbarm T
      • et al.
      Transphyseal reconstruction of the anterior cruciate ligament in prepubescent athletes.
      • Aichroth PM
      • Patel DV
      • Zorrilla P
      The natural history and treatment of rupture of the anterior cruciate ligament in children and adolescents. A prospective review.
      • Ralles S
      • Agel J
      • Obermeier M
      • et al.
      Incidence of secondary intra-articular injuries with time to anterior cruciate ligament reconstruction.
      • Gebhard F
      • Ellermann A
      • Hoffmann F
      • et al.
      Multicenter-study of operative treatment of intraligamentous tears of the anterior cruciate ligament in children and adolescents: comparison of four different techniques.
      • Calvo R
      • Figueroa D
      • Gili F
      • et al.
      Transphyseal anterior cruciate ligament reconstruction in patients with open physes: 10-year follow-up study.
      though it may have been underpowered to demonstrate an effect. For example, post hoc analysis of the adolescent subcohort in the Ralles et al
      • Ralles S
      • Agel J
      • Obermeier M
      • et al.
      Incidence of secondary intra-articular injuries with time to anterior cruciate ligament reconstruction.
      study revealed a difference in the incidence of medial meniscal tears of 10% between those who had surgery within 3 months and those who had delayed treatment, a finding that was not statistically significant. Gebhard et al
      • Gebhard F
      • Ellermann A
      • Hoffmann F
      • et al.
      Multicenter-study of operative treatment of intraligamentous tears of the anterior cruciate ligament in children and adolescents: comparison of four different techniques.
      noted a twofold increase in meniscal pathology in the delayed cohort and Calvo et al
      • Calvo R
      • Figueroa D
      • Gili F
      • et al.
      Transphyseal anterior cruciate ligament reconstruction in patients with open physes: 10-year follow-up study.
      noted a threefold increase in meniscal pathology but neither demonstrated statistical significance, most likely because they were underpowered. The same may be true of the 5.4-times risk of cartilage injury in the delayed cohort in the Cohen et al
      • Cohen M
      • Ferretti M
      • Quarteiro M
      • et al.
      Transphyseal anterior cruciate ligament reconstruction in patients with open physes.
      study which did not demonstrate statistical significance.
      Second, one cannot infer causation from the associations between intra-articular injury and surgical delay noted by several studies. All comparative studies were retrospective and subject to selection bias, measurement bias and design bias. Specifically, surgical decision-making may have accounted for intra-articular pathology sustained at the time of injury. Furthermore, patients who were treated non-operatively and had subsequent surgery to address ACL, meniscus or cartilage pathology may have been more likely to be included in a retrospective study compared with asymptomatic patients who may not have returned for follow-up. Also, activity level during the interval between injury and surgery may have affected the rate of meniscal and/or cartilage damage noted at the time of arthroscopy, however, was not reported in the constituent studies.
      Third, many studies provided aggregate patient age but did not specifically mention skeletal maturity. It is possible that parts of some cohorts included in this study are skeletally mature despite being in the paediatric/adolescent age range. Finally, while an association between surgical delay and the development of subsequent intra-articular pathology might best be studied using a randomised clinical design, this may not be feasible. In addition to the large amount of funding and healthcare resources required for any randomised control trial (RCT), the associations between surgical delay and intra-articular degenerative changes noted in the included studies eliminate clinical equipoise and may make a prospective experimental design ethically unfeasible.
      In conclusion, while the majority of studies either provided sufficient data for post hoc analysis or directly reported significant associations between surgical delay and increased rates of intra-articular pathology, there still exists controversy in the orthopaedic literature regarding this effect. Future prospective research in a uniform cohort of skeletally immature patients with ACL tears may provide more answers to this question, as a randomised experimental design may be financially and ethically unfeasible.

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