Systematic Review

Meniscal Allograft Transplantation: How Should We Be Doing It? A Systematic Review Peter Myers, M.B.B., F.R.A.C.S. (Orth.), F.A.Orth.A., and Francois Tudor, M.B.B.S., M.Sc., F.R.C.S. (Tr & Orth)

Purpose: We undertook a systematic review to assess a number of the technical aspects of meniscal allograft transplantation (MAT) that have not been covered in other reviews. Specific variables studied included the indications for MAT, graft fixation method, rehabilitation protocols, outcome scores, and definition of failure. Methods: We performed a systematic literature review of the PubMed, EMBASE, and Cochrane databases to determine the outcomes of meniscal transplantation at greater than 2 years postoperatively. PRISMA (Preferred Reporting for Systematic Reviews and MetaAnalyses) guidelines were followed with a PRISMA checklist. The search was completed on January 5, 2014. Results: These queries returned 629 results from which 41 articles were identified as meeting the inclusion criteria. No studies in this review were randomized or controlled. Conclusions: MAT is a worthwhile procedure, with evidence that it provides pain relief and improved function, and good results reported in mid- to long-term studies. The procedure should be considered only in a patient with localized pain and a stable (or stabilized) and well-aligned (or realigned) knee. The controversial areas studied in this review include the following: there is no evidence to support fixation with either bone plugs or soft tissue; there is no standardized rehabilitation program, but it appears that full weight bearing by 6 weeks is not detrimental; and a clear and uniform definition of failure and use of consistent outcome scores would aid future reporting and analysis of the results of meniscal transplantation. Level of Evidence: Level IV, systematic review of Level II to IV studies.

T

he loss of a meniscus in a young and active person can lead to progressive pain, loss of function, and arthrosis in the involved knee compartment.1-3 The risk of the development of osteoarthritis seen on radiography and knee pain after total meniscectomy has been reported to be as much as 14 times higher in comparison with controls.4 The intact meniscus has a role in load distribution, joint congruity, stability, lubrication, and proprioception.5,6 An improved understanding of these important functions has led to a move toward meniscal preservation with arthroscopic repair whenever possible, generally with excellent results.7,8 However, despite the improved repair techniques available,

From Brisbane Orthopaedic & Sports Medicine Centre, Brisbane, Queensland, Australia. The authors report that they have no conflicts of interest in the authorship and publication of this article. Received July 12, 2014; accepted November 13, 2014. Address correspondence to Dr Peter Myers, M.B.B., F.R.A.C.S. (Orth.), F.A.Orth.A., Brisbane Orthopaedic & Sports Medicine Centre, Level 5, Specialist Centre, 259 Wickham Terrace, Brisbane Qld 4000, Australia. E-mail: [email protected] Ó 2015 by the Arthroscopy Association of North America 0749-8063/14601/$36.00 http://dx.doi.org/10.1016/j.arthro.2014.11.020

some meniscal tears are irreparable, resulting in total or subtotal meniscectomy. The advent of meniscal allograft transplantation (MAT) in 1984 meant that there was a viable treatment option available for patients with symptomatic knees after meniscectomy. A number of recent reviews have focused on the survival and failure rate of MAT.9-11 These report good mid- to long-term results that provide patients with improvement in pain and function. However, many review articles and original articles present results of MAT combined with other procedures, such as surgical correction of limb malalignment, ligamentous instability, and treatment of cartilage defects. Most describe huge variations in surgical technique, graft type, rehabilitation protocols, and surgeon/patient expectations. Finally, many authors accept different definitions of failure. Although there are many different techniques for MAT, we question whether it is possible to determine from the literature which methods produce the best results. Most of the literature on MAT reports on graft survival, but we have chosen to focus on issues that appear undecided, such as patient selection, graft type and operative techniques, rehabilitation protocols, and surgeon/patient expectation. The purpose of this

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systematic review was to assess a number of the technical aspects of MAT that have not been covered in other reviews. Specific variables studied include the indications for MAT, graft fixation method, rehabilitation protocols, outcome scores, and definition of failure.

Methods Search Strategy and Criteria We performed a systematic literature review to determine the outcomes of meniscal transplantation at greater than 2 years postoperatively. PRISMA guidelines (Preferred Reporting for Systematic reviews and MetaAnalyses) were followed with a PRISMA checklist. The search was completed on January 5, 2014. PubMed (January 1, 1966 to January 1, 2014), EMBASE (January 1, 1974 to January 1, 2014), and Cochrane databases (February 1, 1995 to January 1, 2014) were queried with use of the terms ([meniscus OR meniscal] AND allograft AND transplant). Disagreements among authors regarding study inclusion were decided by the senior author (P.M.). The references of all included articles were reviewed to ensure that there were no articles missed by the initial search. The most recent report was used in the case of multiple publications studying the same participant population unless different variables or outcomes were reported. Inclusion criteria included human data only, primary outcome of meniscal transplant status, minimum of 2 years’ mean follow-up, primarily adult patients, cohort size of greater than 10 patients, less than 30% loss to follow-up, and English-language publications. Exclusion criteria included non-Englishelanguage articles; less than 2 years’ mean follow-up; review articles; Level V evidence; articles discussing basic science, biomechanics, and anatomy; surgical technique articles; and letters to the editor. All inclusion and exclusion criteria were defined before the literature search was performed. To assess the methodological quality of the collected data, the Coleman methodology score (CMS)12 and the modified Coleman methodology score (MCMS) according to Kon and Verdonk,13 were determined for each study by one independent reviewer (F.T.).

Results These queries returned 304 results from PubMed, 227 results from MEDLINE, and 98 results from EMBASE. The Cochrane database yielded no other studies. Fortyone articles were identified as meeting the inclusion criteria.14-54 Table 1 provides further details of these articles. No studies in this review were randomized or controlled. Twenty-six of the included studies were prospective cohort studies or prospective case series, and 15 were retrospective case series.

The follow-up period ranged between 24 months41-52 and 14 years,50 with an overall average of 4.8 years. Mean patient age in single trials ranged between 19.8 years and 48 years, with an overall mean of 33.7 years. Indications All articles report unicompartmental pain after previous total or subtotal meniscectomy as one of the main indications for MAT. Earlier studies excluded patients with malalignment or instability, but recent advances in surgical techniques allow most authors to consider correcting these problems during transplantation and to include these patients in their research. Three authors included persistent swelling or effusions with activity in their indications. Chondral damage is an area of controversy, with one study excluding any patients with greater than Outerbridge grade II34; however, a number of authors performed MAT in any patient with Outerbridge III or less,27,30,38,42 and some reported MAT in patients with lesions up to Outerbridge grade IV.32,36,37,41,53 Marcacci and Zaffagnini reported that they perform MAT only in patients with a healthy contralateral knee.15,23 Many authors included age in their indications for transplantation, with 4 just commenting “young” patients and others defining an actual age range: 15 to 55 years,15,23 20 to 45 years,25 less than 45 years,16,49 less than 50 years,38,44 and less than 55 years.33,35 Some authors offered MAT to patients only after an acceptable period of conservative treatmentdusually greater than 6 months.25,26,29,40,53 One article included only patients with a body mass index less than 30.20 Most authors considered previous infection in the knee, inflammatory arthritis, neuropathy, and evidence of osteonecrosis along with uncorrected malalignment or instability as contraindications to MAT. In summary, it seems reasonable to perform MAT in patients after meniscectomy who have continued pain in the affected compartment and are too young to consider arthroplasty in a stable normally aligned limb after a satisfactory trial of nonoperative management. Graft Type Graft preservation is an area that has become more consistent over time. Initial experience with lyophilized grafts resulted in higher failure rates, and they are no longer used. The most commonly used grafts are fresh frozen and nonirradiated or noneantigen matched, with 29 articles reporting the use of this graft preservation for all or most of their menisci. Eight reported a combination of fresh frozen and cryopreserved grafts, and only 2 used irradiated fresh frozen grafts. Verdonk reported the use of viable grafts in 2 articles.43,45 One article did not report the type of preservation used for the grafts. Irradiation is no longer used because it was found to be unnecessary and hazardous to graft survival resulting from detrimental effects on the mechanical structure of the meniscus.55

Table 1. Description of Articles Included in the Study Including Data on Number of Cases, Graft Type, Sizing Method, and Fixation Technique, Outcome Measures Used, and MRI Findings if Reported First Author

Level of Evidence

No. of MAT Procedures

14

Yoon

III

91

15

Marcacci

IV

12

16

Roumazeille

IV

22

17

Chalmers

IV

14

18

Abat

II

88

19

Saltzman

20

Abat

22

II

88

Surgical Technique

Associated Procedures

Lateral: soft-tissue ACL, cartilage fixation Medial: repair bone plug IOS No bone plugs ACL, AIS (UltraBraid/Ultra osteochondral Fast-Fix [Smith & scaffold Nephew, Andover, insertion, ACI MA]), anterior horn to remnant of native meniscus OIS No bone plugs 5 ACL AIS (Fast-Fix)

Outcome Scores

Indications/Inclusion Criteria

Sizing

Graft Type

VAS, IKDC, Pain
instability Lysholm, Tegner

MRI

VAS, IKDC, Lysholm, Tegner, WOMAC

Pain after meniscus loss > 75%, stable knee or ACL reconstruction already done, age 15-55 yr, healthy contralateral knee

Radiograph Fresh frozen (80 C), not irradiated, (Pollard) and not antigen anthropometric matched, donors parameters 15-35 yr

KOOS, IKDC

Pain/functional sequelae Radiography and caused by previous total/ patient weight subtotal meniscectomy, < 45 yr

Fresh frozen (80 C)

Fresh frozen (80 C), not irradiated, not antigen matched

MRI Findings Absolute extrusion in 6 of 24 (25%) lateral cases and 4 of 11 (36%) medial cases Not reported

Average 3.6 mm and percentage graft extrusion 46% at final follow-up Total extrusion in 2 patients No correlation between extrusion and outcome Not reported

KOOS, IKDC, Pain, normal alignment, Radiography and Fresh frozen (80 C), not irradiated, Lysholm, Tegner stable knee or correction patient weight not antigen to stable knee matched Preoperative participation in high-level sports and motivation to return to similar level 2 groups: bone plugs ACL, microfracture VAS, Lysholm, Pain, concomitant ACL Radiography and Fresh frozen (80 Not reported and no bone plugs Tegner reconstruction if anthropometric C), not irradiated, IOS and AIS (Fastnecessary parameters not antigen Fix) matched Not reported Lateral: 5 keyhole, 1 ACI ACL: SF-12, Lysholm, Pain Radiography Fresh frozen bridge-in-slot microfracture, IKDC, KOOS (Pollard) (80 C) Medial: 12 double osteochondral plug, 1 bridge-inallograft, PCL: slot thermal IOS shrinkage Suture only: 72.7% of cases 2 groups: bone plugs ACL, microfracture Lysholm Pain, BMI < 30 Radiography Fresh frozen had major extrusion and no plugs IOS (Pollard) (80 C), not irradiated, not Bone plug: 30.9% of cases and AIS (Fast-Fix) antigen matched had major extrusion (P < .001) No correlation with extrusion and Lysholm score Bridge-in-slot and double bone plug

ACL, osteochondral graft, microfracture, DFO

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Table 1. Continued First Author

Level of Evidence

No. of MAT Procedures

21

Kim

IV

110

22

Koh

IV

99

23

Marcacci

IV

32

No bone plugs 8 ACL, 6 HTO, AIS (UltraBraid/Ultra 6 DFO Fast-Fix), anterior horn to anterior capsule with AIS and OIS

24

Kim

IV

29

2 trough, 27 keyhole method IOS

25

Ha

IV

22

Bone plugs (smaller 2 osteotomies, 15 posterior to allow ACL, 2 PCL, passing) 4 PLC IOS

Surgical Technique

Associated Procedures

Lateral: 2 bony trough, 81 keyhole method Medial: 3 trough, 9 keyhole, 15 bone plugs IOS Lateral: keyhole 15 ACL, 9 Medial: double bone osteochondral plug autografts IOS

None

Outcome Scores Lysholm, Knee Society pain score

Indications/Inclusion Criteria Swelling and pain during ADL

Sizing Radiography (Pollard)

Graft Type

MRI Findings

5 cryopreserved, 105 Almost all grafts showed fresh frozen some degree of extrusion: mean 3.7 mm, 42.6% graft extrusion

Lateral menisci extruded: mean 4.7 mm (percent extrusion 52.0%), medial 2.9 mm (percent extrusion 31.2%) (P < .001 for measure and percent) Lysholm not correlated to extrusion distances 69% of all grafts extruded VAS, IKDC, Pain, stable knee or ACL Radiography Fresh frozen (8 medial [50%], 14 Lysholm, reconstruction already (Pollard) and (80 C), not irradiated, not lateral [87%]) Tegner, done, age 15-55 yr, anthropometric antigen matched, No significant difference in WOMAC, SF-36 healthy contralateral knee parameters donors 15-35 yr outcome scores MRI showed a significant decrease of femoral and tibial cartilage degeneration from baseline to 36-mo follow-up Lysholm, HSS Swelling and pain during Radiography 2 cryopreserved 27 Some degree of extrusion in score ADL (Pollard) fresh frozen all cases Mean extrusion: 4 mm, percentage graft extrusion: 45.4% Mean extrusion: 4.35 mm Lysholm, IKDC Pain > 6 mo, age 20-45 yr, Radiography Fresh frozen and percent extrusion active lifestyle, acceptable (Pollard) (80 C) 43% limb alignment Arthrosis progression seen in 4 of 18 (22.2%) No significant correlation with Lysholm/IKDC/ degenerative arthritis, and extrusion Lysholm

Not reported

Radiography (Pollard)

Fresh frozen (80 C)

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Table 1. Continued First Author

Level of Evidence

No. of MAT Procedures

26

Jang

III

36

Lateral: keyhole Medial: modified double bone plug

27

Zhang

IV

18

Double bone plug Inside-out, AIS and OIS

28 Gonzalez-Lucena

IV

33

No bone plugs. Inside-out sutures

29

Ha

IV

60

Lateral: keyhole Medial: modified double bone plug

30

Vundelinckx

IV

50

2 bone plug fixation 2 HTO, 2 Lysholm, Tegner, 48 soft tissue fixation microfracture, 1 VAS, KOOS, AIS posteriorly, Ilizarov varus SF-36 middle part IOS, correction (5 anteriorly OIS ACL, 1 PCL at separate operations)

Surgical Technique

Associated Procedures ACL reconstruction, microfracture, PCL reconstruction

7 ACL

8 ACL recon, 8 microfrac, 9 chondroplasty

11 ACL, 3 PLC, 2 PCL, 2 microfracture, 2 ACI

Outcome Scores Lysholm

Lysholm, IKDC, KOOS, VAS

Lysholm, Tegner, VAS Pain

Lysholm

Indications/Inclusion Criteria

Sizing

Graft Type

Fresh frozen Moderate to severe pain for Group 1: (80 C) > 6/12 mo Radiography (Pollard). Group 2: Radiography (Pollard) decreased by 5%

MRI Findings Group 1 (conventional Pollard): mean extrusion, 4.05 mm, 46.68% Group 2 (Pollard, 5%): mean extrusion 3.68 mm (P > .05), 35.18% (P ¼ .037) 15 major extrusions in group 1, 12 in group 2 No correlation between extrusion and outcome scores Partial extrusion in 11 (65%), normal in 6 No complete extrusion seen

Radiography Fresh frozen (80 Pain or osteoarthritis, C), low-dose (Pollard) articular cartilage irradiation (1.5 Outerbridge grade III or mrad), donor less, normal alignment < 40 yr and stable or reconstructed ligaments, young patient Well-aligned knee, ACL X-ray (Pollard) and Fresh-frozen (80 Meniscal extrusion was a could be reconstructed at anthropometric C) non-irradiated, constant finding, with a time of transplant parameters non-antigen mean of 36.3% of the total matched meniscus extruded in either lateral or medial menisci 3.87 mm, 42.1% extrusion, Moderate to severe pain for Radiography Fresh frozen 7 cases (19.4%) minor and 27 > 6/12 mo (Pollard) (80 C) (75%) major extrusion No cartilage degeneration in 28 (77.8%), but 8 showed further degeneration No correlation between extrusion and outcome Pain, stable knee, no Calibrated Cryopreserved, Not reported malalignment, articular computed donors < 45 yr cartilage Outerbridge III tomographic or less, young patient scan

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Table 1. Continued First Author

Level of Evidence

No. of MAT Procedures

31

LaPrade

IV

40

Lateral: bone trough Medial: double bone plugs IOS

32

Stone

IV

119

33

Alentorn-Geli

IV

37

34

Lee

III

43

Lateral: 3-tunnel Osteochondral technique, bone graft, block in both microfracture, horns HTO, ACL Medial: 3-tunnel technique, no bone blocks No bone plugs AIS (Fast-Fix) posterior horn, rest IOS Lateral: keyhole Medial: double bone plug IOS

35

Van der Wal

IV

63

Open, no bone plugs, multiple sutures

36

Rue

IV

31

37

Farr

IV

36

ACI, osteochondral Lysholm, IKDC, Initially: Lateral: keyhole graft, HTO SF-12 Medial: double bone plug Then all with bridgein-slot Slot-technique ACI, HTO, ACL Lysholm, modified Pain and focal chondrosis, Radiography (Pollard) IOS Cincinnati, VAS ligamentous stability and alignment normal or corrected at time of surgery

Surgical Technique

Associated Procedures

Outcome Scores IKDC, Modified Cincinnati

Tegner

Lysholm, IKDC, VAS

Lysholm

Lysholm, IKDC, KOOS

Indications/Inclusion Criteria

Sizing

Graft Type

MRI Findings

Fresh frozen (80 C), donors 12-40 yr

Not reported

Fresh frozen (80 C) 94, cryopreserved 24, irradiated 1

Not reported

Pain, good alignment, stable ? Radiography knee ligaments, age < 50(Pollard) 55 yr

Fresh frozen and cryopreserved.

Not reported

Pain, chondral damage, Outerbridge II or less, joint stability, normal alignment

Fresh frozen (80 C)

Pain; effusion after activity, skeletal maturity Ligament stability or reconstruction at time of surgery Pain, Outerbridge III or IV Donor/recipient sex, height, changes in the respective weight compartment, ROM at least 90

Radiography (Pollard)

Disabling compartmental No matching OA after meniscectomy; patients < 55 yr, mixture of normal alignment/ malaligned and ACL deficient/stable knees Pain with combined articular Not reported cartilage injury, normal alignment (or correction) and stable knee

Cryopreserved

Mean extrusion at 1 yr 3.03 mm 26 (60%) had no extrusion, 17 (40%) had extruded grafts No relationship between extrusion and poor outcome Not reported

Cryopreserved, fresh frozen

Not reported

Fresh frozen, not irradiated

Not reported

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Table 1. Continued First Author

Level of Evidence

No. of MAT Procedures

38

Hommen

IV

22

39

Kim

IV

14

40

Sekiya

IV

32

41

Stone

IV

47

42

Cole

IV

44

Lateral: keyhole 19 (47.5%) Medial: double bone articular plug cartilage repair IOS

43

Verdonk

IV

42

No bone plugs, 11 HTO, 3 ACL, 1 KOOS, HSS score anteriorly and DFO posteriorly sutured to remnant horns on tibia LCL/MCL femoral insertion osteotomy AIS

Surgical Technique

Associated Procedures

Outcome Scores

Indications/Inclusion Criteria

Sizing

If indicated, medial epicondyle osteotomy Lateral: trough or bone plug, 5 suture only Medial: 3 double bone plug, 8 allsuture technique IOS 2 trough method, 12 3 osteochondral autografts keyhole IOS

Lysholm, modified Pain, age < 50 yr, mild to Radiography pain score advanced arthrosis and > 2 (Pollard) mm joint space on radiography, surgically correctable malalignment or instability included

5 double bone plugs, 12 bone bridge/ trough, 8 no bone plugs IOS No bone plugs ACL, IOS microfracture, HTO

Pain during ADL, failed trial of Radiography conservative therapy (Pollard)

Lysholm

Not reported

Lysholm, Tegner, IKDC, Noyes score, VAS, KOOS, SF-36

Pain and swelling during ADL

Radiograph (Pollard)

Not reported Pain, ROM at least 90 , articular cartilage damage, degenerative changes, Outerbridge III or IV Pain with relatively wellRadiography preserved articular cartilage (Pollard) < grade III change, normal alignment, and stable knee (or correction at time of grafting) Pain, young/middle-aged Not reported patient, Malalignment or instability corrected at the time of MAT

Graft Type

MRI Findings

Cryopreserved

Not reported

Cryopreserved, fresh Mean extrusion 2.6 mm frozen No gross extrusion All showed sound peripheral healing Cryopreserved no Not reported irradiation

29 (62%) cryopreserved, 18 (38%) fresh frozen Cryopreserved, fresh frozen (< 20%)

Not reported

Viable graft, donor age < 45 yr, no corticosteroids or cytostatic drugs given

12 (70%) partial extrusion, normal in 4 (24%) No change in graft position over 10 yr in 6 of 17 (35%), progressive extrusion in 10 of 17 (59%) 2 knees had tearing of graft

Not reported

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Table 1. Continued First Author

Level of Evidence

No. of MAT Procedures

44

Noyes

III

40

Lateral: keyhole 16 osteochondral Medial: double bone graft, 4 ACL, 1 plug PCL IOS

45

Verdonk

IV

100

46

Sekiya

III

28

47

Yoldas

IV

34

48

Ryu

III

29

No bone blocks, 15 HTO, 2 DFO, 3 Survival analysis anteriorly and was based on ACL, 4 posteriorly sutured osteochondral specific clinical to remnant horns plug, 3 end points, with on tibia failure of the microfracture LCL/MCL femoral allograft defined insertion as moderate osteotomy occasional or AIS persistent pain or as poor function Lateral: trough All ACL IKDC, SF-36 Medial: no bone plugs IOS Lateral: trough 20 ACL Lysholm, SF-36, activities of daily Medial: bone plugs IOS living/sports assessment, radiological findings, and stability Lateral: trough 12 ACL Lysholm, Tegner, Medial: initial medial IKDC, VAS femoral epicondyle osteotomy, then deep MCL release Bone blocks IOS

Surgical Technique

Associated Procedures

Outcome Scores

Indications/Inclusion Criteria

Rating system that Pain, age < 50 yr, no combined radiographic evidence of subjective, advanced arthrosis, > 2 clinical, and mm joint space on MRI factors radiography

Pain, young patient (not old enough to consider joint replacement), with good alignment and stable joint (or corrected at surgery)

Sizing Radiography (Pollard)

Not reported

Pain with symptomatic Radiograph instability caused by ACL (Pollard) injury during ADL or sports Pain
symptomatic Radiograph instability caused by ACL (Pollard) injury during ADL or sports

Not reported

Not reported

Graft Type Cryopreserved

Viable graft, donor age < 45 yr, no corticosteroids or cytostatic drugs given

MRI Findings Mean extrusion in coronal plane 2.2 mm 17 (59%) had no displacement, 11 had minor displacement Sagittal plane mean extrusion 1.1 mm 25 (86%) had no displacement, 3 had minor displacement, 1 had major displacement (9 mm) Not reported

Cryopreserved (80 C), not irradiated

Not reported

Fresh frozen (80 C)

Not reported

Not reported

Not reported

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Table 1. Continued First Author

Level of Evidence

No. of MAT Procedures

49

Van Arkel

III

63

No bone blocks IOS

50

Wirth

III

23

51

Rath

III

23

52

Stollsteimer

IV

23

53

Cameron

IV

67

54

Van Arkel

III

23

Open All ACL Not reported Not reported No bone plugs, multiple sutures Radiography SF-36 Pain, instability or Lateral: bone trough 11 ACL, 3 partial malalignment addressed (Pollard) Medial: double bone meniscectomies, plugs 1 tibial tubercle at or before transfer transplantation IOS Double bone plugs Lysholm, Tegner, Pain Radiography IOS IKDC Open, distraction 5 ACL, 34 HTO or Modified Lysholm, Pain after conservative Not reported device, no bone DFO (valgus or Tegner treatment, unicompartmental OA blocks, sutures varus), 7 ACL (Outerbridge II/IV) and with HTO too young/active for arthroplasty Malalignment or instability treated at time of transplantation Open, no bone Not reported Not reported blocks, sutures

Surgical Technique

Associated Procedures

Outcome Scores Survival analysis used persistent pain or mechanical damage as clinical criteria of failure Lysholm

Indications/Inclusion Criteria Pain, < 45 yr, normal alignment, stable joint

Sizing

Graft Type

MRI Findings

None used

Cryopreserved

Not reported

17 lyophilized, gamma sterilized, 6 deep frozen all grafts were deep frozen and cryopreserved

Not reported

Not reported

Cryopreserved, not irradiated Gamma irradiation and frozen 70 C

Not reported

Fresh frozen- 80 C

Not reported

Not reported

ACI, autologous chondrocyte implantation; ACL, anterior cruciate ligament (reconstruction); ADL, activities of daily living; AIS, all-inside sutures; BMI, body mass index; DFO, distal femoral osteotomy; HSS, Hospital for Special Surgery; HTO, high tibial osteotomy; IKDC, International Knee Documentation Committee; IOS, inside-out sutures; KOOS, Knee Injury and Osteoarthritis Outcome Score; LCL, lateral collateral ligament; MAT, meniscal allograft transplantation; MCL, medial collateral ligament; MRI, magnetic resonance imaging; OA, osteoarthritis; OIS, outside-in suture; PCL, posterior cruciate ligament (reconstruction); PLC, posterolateral corner (reconstruction); ROM, range of motion; SF-12, Short Form-12; SF-36, Short Form 36; VAS, visual analog scale; WOMAC, Western Ontario and McMaster Universities Osteoarthritis Index.

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Graft sizing, initially considered unnecessary, is now recognized to be important to the successful outcome of MAT. Twenty-one authors reported using the method of Pollard et al.56 for radiographic sizing. In an effort to reduce meniscal extrusion, Jang et al.26 reduced the Pollard measurements by 5%. Other authors combined radiographic measurements and recipient anthropometric parameters in an attempt to improve graft sizing. One article reported the use of magnetic resonance imaging (MRI),14 and one used calibrated computed tomographic scans30 for sizing. One article reported the use of recipient anthropometric parameters alone,32 and 2 studies used no matching.35,49 Nine articles did not report the sizing method used. In summary, the graft of choice would be fresh frozen and not irradiated, unless viable menisci are available. Graft sizing should be performed, and most commonly the Pollard method is used with successful results. Surgical Techniques Originally performed through an open approach35,50,53,54 with femoral condyle osteotomy including the collateral ligaments44,45,49 or the use of distraction devices,54 MAT is now performed as an arthroscopically assisted procedure requiring a miniarthrotomy for graft insertion; this is supported by the literature, with 37 authors reporting the use of this approach. Graft fixation varies, with some surgeons using bone blocks and some using soft tissueeonly fixation. Typically, fixation on the medial side is with double bone plugs through tunnels drilled to the anterior and posterior horns of the residual native meniscus. This was reported in 21 articles. The use of soft tissueeonly fixation on the medial side was reported in 15 articles. On the lateral side, because the anterior and posterior horns are physically closer, often only a single bone block is required. A number of different configurations may be useddincluding a slot key, trough, or dovetaildall without tunnels; these methods were used in 20 studies. Soft tissueeonly fixation on the lateral side was also reported in 15 articles. Surgeons may differ their approach to fixation, often depending on concomitant procedures being performed at the time of transplantation; 4 articles reported a mixture of both bone and soft tissue fixation (Fig 1). Cadaveric studies have shown that bony fixation of the meniscal horns is required to restore near-normal tibial contact forces and recreate the meniscal hoop stresses and that this is not achieved adequately in suture-only fixation.57,58 However, this does not appear to be confirmed in all the human studies identified in this review because either type of graft fixation results in similar improvements in patient symptoms and good mid- to long-term graft and knee survival.

Fig 1. Lateral and medial meniscus transplants in preparation preoperatively. The lateral transplant with a single bone block prepared for a “slot” technique and the medial transplant with separate anterior and posterior bone blocks. There are 4 sutures on the lateral meniscus allograft; the 2 on the bone block (open arrows) are to facilitate adaption of the bone block into the slot; these are passed through tunnels extending from the anterior of the tibia and into the anterior and posterior areas of the slot. The posterolateral suture (solid white arrow) is used to aid bringing the graft into the joint in the correct position; both limbs of the suture are passed separately through the posterolateral aspect and are retrieved through the incision used for the other inside-out sutures. The last suture is on the allograft attachment of the ligament of Wrisberg, (black solid arrow). This is not always present but when it is, the senior author (P.M.) prefers to attach it to the recipient’s ligament of Wrisberg to aid fixation.

One study compared 2 matched groups with bone fixation or soft tissueeonly fixation,18 finding that the suture-only group had a meniscectomy rate of 9% (3 of 33 patients), whereas the bone plug meniscectomy rate was 3.6% (2 of 55 patients). This was not found to be statistically significant, although the authors commented that it may have reached significance if study numbers had been higher. There was no significant difference in the rate of failure of fixation. MRI examination of bone plug and soft tissue fixation techniques showed extrusion with both techniques. Five authors reported extrusion in their cohorts of soft tissueeonly fixation, and 8 authors reported extrusion in their bone plug fixation cohorts. One author compared the degree of extrusion in 2 groups: one with bone plug fixation and the other with suture-only fixation.20 The study found that 72.7% of the suture-only cases had major extrusion, whereas only 30.9% of the bone plugeonly cases had major extrusion (P < .001). However, there was no correlation with extrusion and Lysholm score in this study, and other authors reported that when extruded grafts were compared with nonextruded grafts, extrusion did not adversely affect patient outcomes.14,16,22,23,26,29

MENISCAL ALLOGRAFT TRANSPLANTATION

Traditional open suture techniques have been replaced with inside-out arthroscopic sutures, the use of which was reported in 29 articles. Newer techniques of repair using all-inside sutures were reported in 10 articles. At present, the data do not appear to support one technique of meniscal transplantation over another. If graft extrusion is identified as a risk factor for long-term failure, it would appear that bone plug fixation, with its lower rate of extrusion, may become the fixation method of choice. Associated Surgical Procedures Meniscal transplantation is commonly carried out with other procedures, and only 11 articles reported the results of MAT alone, either as a cohort receiving MAT in isolation or in comparison with other patients undergoing combined procedures. Most frequently, anterior cruciate ligament (ACL) or revision ACL reconstruction is performed during MAT, and this was reported in 28 articles. Procedures to repair or regenerate cartilage or grafting of defects were reported in 17 articles, and osteotomies around the knee were reported in 12 articles. Some patients may have undergone multiple procedures at the same time as transplantation. We believe that the results of isolated transplantation would be most indicative of the success of the procedure, because it is impossible to differentiate the benefit that patients may gain from MAT when combined with the pain relief, improved stability, offloading, and chondral longevity achieved from the associated operations. Unfortunately, it is difficult to determine the results of any isolated transplantation procedures from most of the studies. Many authors found no difference between patients who underwent isolated procedures and those who underwent combined surgery22,23,36,37,49; however, a recent publication with medium-term results reported that visual analog scale (VAS) (P ¼ .039) and Lysholm (P ¼ .022) scores were significantly better in the isolated group of patients compared with the group undergoing combined procedures, although the Tegner and International Knee Documentation Committee (IKDC) scores and range of motion were not.14 Other authors only reported the results of isolated meniscal transplantation procedures, with good improvement in symptoms and function.24,40 Verdonk et al.48 went as far as reporting the mean survival of isolated lateral and medial meniscal transplants as 11.4 years and 10.7 years, respectively. The results of isolated and combined procedures appear similar, suggesting that concomitant joint stabilization, correction of malalignment, and cartilage regeneration procedures may be carried out with no detrimental effect on the long-term result of MAT.

11

Rehabilitation The fine details of rehabilitation programs followed in each study differed. However, 28 of the articles had their patients fully bearing weight and 29 aiming for a range of motion greater than 0 to 90 by the end of 6 weeks. Chalmers et al.17 allowed full weight bearing to progress after the second postoperative week, but 5 study authors kept their patients at less than full weight bearing for longer than 6 weeks. Twelve authors prescribed the use of a removable brace during the rehabilitation period. Return to running and other training was not clearly reported in many articles but was allowed before the fourth month in 10 of the studies and after this period in 11 studies. Five studies did not report a rehabilitation protocol. Although rehabilitation protocols vary greatly between institutions, it appears that patients can safely bear full weight and aim for a range of motion around 0 to 90 by 6 weeks, depending on concomitant procedures. Return to running and other sports should be dependent on an individual patient achieving milestones defined by muscle strength, control and endurance, and adequate healing of the graft and any other procedures performed. Clinical Outcomes All but one of the studies reported the use of validated scoring systems to measure patients’ clinical outcomes. In all, 10 different scoring systems were identified in the MAT literature, with many authors using more than one score. The Lysholm score (modified) was used in 30 studies, the IKDC score was used in 17 studies, the Tegner activity score was used in 13 studies, the pain VAS was used in 12 studies, the Knee Injury and Osteoarthritis Outcome Score (KOOS) was used in 8 studies, either the Short Form (SF)-12 or SF-36 was used in 8 studies, the modified Cincinnati score was used in 3 studies, and the Western Ontario and McMaster Universities (WOMAC) and Hospital for Special Surgery (HSS) scores were used in 2 studies each. All studies reported improvements in pain, function, and activity, although this improvement tended to decay with time,35 a finding confirmed in a recently published meta-analysis,9 and some showed improvements in pain and function but not in the Tegner activity score.30,32 Standardization of outcome scores would enable easier comparison of the published results of meniscal transplantation. Because there are no outcome scores validated for use in these patients, until one is developed we must consider the most frequently used scores. These are the Lysholm, IKDC, VAS, and Tegner scores, all of which are acceptable for evaluation of MAT outcomes. We would urge authors to consider the reporting of these scores alongside any other scores

12

P. MYERS AND F. TUDOR

they prefer in future publications of meniscal transplantation outcomes. Radiological Outcomes Most authors reported the use of radiography or MRI, or both, as part of their follow-up. Comparison of the postoperative radiographs with the contralateral knee or preoperative radiographs was used to determine loss of joint space and thus can be extrapolated to confirm progression of osteoarthritis in the transplanted knee. Measurements of joint space and the use of the IKDC or Fairbank’s radiological criteria were reported in 9 articles. Medium- to long-term surveillance of patients undergoing MAT showed only slight or no progressive loss of joint space in most of the patients.43,46,47,51 MRI or MR arthrography was used most commonly, with 17 studies reporting such use. MRI regularly showed good healing and graft incorporation,16,25 and correlation with secondlook arthroscopy confirmed the accuracy of MRI at detecting meniscal tears.20,21 Many authors reported graft extrusion, although this was not correlated with any difference in function in comparison with nonextruded grafts14,15,20,22,26,29,34 and did not appear to have a detrimental effect on medium- and long-term survival. Two studies used MRI to confirm cessation of articular cartilage degeneration after MAT in most of their study participants.23,25 MRI was shown by many of the studies to be accurate for identifying meniscal healing as well as the presence of tears, and we would recommend its use for routine follow-up of meniscal transplantation, as well as for investigation of symptomatic patients. Expectations Meniscal transplantation was introduced as a salvage procedure for patients with symptomatic knees after meniscectomy. As such, surgeon and patient expectations in the early stages of MAT were focused on pain-free living and gentle activities in an effort to protect the graft and knee from future deterioration. Active individuals, however, will want to return to previous sports if possible. Increasingly, authors have been pushing the indications for MAT, with 2 groups expecting and achieving a return to high-level sports.15,17 However, the data reported in these studies was for the short term only (mean follow-up, 36 and 39.4 months, respectively). Other authors allow a return to noncontact sports but prohibit strenuous cutting and twisting; this was reported in 11 studies. There remains a concern in some groups that the longevity of the meniscus will be affected by strenuous activities, and longer term follow-up is required to determine if any return to sports is advisable. Failures and Complications Seven authors did not report failure rates or complications. The search identified a total of 1,849 meniscal

allografts with a total 104 reported partial or subtotal meniscectomies (5.6%), with total graft removal required in 36 (1.95%) and revision MAT in 13 (0.7%) cases. Meniscal repair or refixation was required in 39 (2.1%) patients. Conversion to joint arthroplasty was reported in 14 patients (0.8%). Authors defined graft failure in many different ways, but if we accept subtotal or total removal of the graft, graft revision, or conversion to arthroplasty as failure, the total failure rate was 9.0%. Manipulation or arthrolysis for postoperative stiffness was required in 35 (1.9%) patients and synovectomy was needed in 3 patients (0.2%). Infection was reported in 13 patients, with an overall infection rate of 0.7%, which was mostly treated with arthroscopic washout, and the majority of grafts were retained. In total, complications or failures were reported in 486 patients (26.3%). What Is Graft Failure? As discussed, many authors used grossly different findings to define failure, some calling structural graft damage alone failure. Others reported failure as irreparable graft damage or poor patient-reported outcomes scores, or both. The latter would potentially give higher failure rates than would the former. These differences make it extremely difficult to analyze results accurately. Because meniscal transplantation is a procedure for active patients experiencing pain and functional disability after meniscectomy, patient-reported outcome and pain and activity scores are undeniably linked to the perceived success or failure of the operation. However, in follow-up studies, the structural integrity of the graft is as important as patient symptoms and must also be reported clearly. This review has revealed that some patients may remain symptomatic despite a fully healed and functional graft and some may be entirely asymptomatic in the presence of graft failure. We suggest that in future studies reporting on MAT survival, the terms “symptomatic” and “mechanical” failure could be used. A graft achieving patient-reported scores equal to or less than preoperative scores should be defined as a symptomatic failure. Mechanical failure should be defined as a lack of graft healing, graft tearing, or failure of fixation seen on MRI or at arthroscopy; progression to KellgrenLawrence grade 4 osteoarthritis59 on weight-bearing radiographs; removal of the transplant; revision meniscal transplantation; or conversion to arthroplasty. Study Quality Assessment Of the 41 studies evaluated, 6 were retrospective case series and 35 were prospective cohort studies or prospective case series. The Coleman Methodology Score (CMS) is a method of analyzing the quality of studies reviewed and is accepted as both accurate and reproducible.12 The CMS produces a score of between 0 and 100, with a perfect score of 100 representing a study

MENISCAL ALLOGRAFT TRANSPLANTATION

design that avoids the influence of chance, various biases, and confounding factors. The modified CMS (MCMS) was described by Kon et al.13 to better assess cartilage-related studies. The average original CMS was 46.1
9.0 (range, 28 to 59). The average MCMS was 43.5
9.4 (range, 25 to 58).

Discussion MAT has been shown by previous systematic reviews to be a safe and successful operation for most patients. A recent systematic review concluded that more than 60% of patients undergoing isolated MAT had a successful result (with more recent literature reporting better success rates resulting from advances in techniques) and graft survival of up to 76% at 10 years.60 Other reviews have similar conclusions, with improvement in patient symptoms and function.9,10 However, the addition of other procedures complicates analysis of the results. It would be expected that performing concomitant joint alignment and stabilization procedures would improve the survival of grafts. It is reasonable to presume that performing MAT on knees with chondral defects requiring repair or regenerative techniques may be more likely to lead to functional deterioration with time because the knee was in worse condition before transplantation. However, this is not supported by the literature in this review, with short-term studies showing improvement in patient symptoms and function,36,37 and one study reporting a 79.9% success rate with a mean Kaplan-Meier estimated survival time of 9.9 years in patients undergoing MAT and articular cartilage repair.32 The question about graft storage appears to have been answered, with most authors using fresh frozen grafts without irradiation or antigen matching. Viable grafts produce results similar to those of fresh frozen grafts, but availability of viable tissues is an issue stopping many authors from using this type of graft preparation. Controversy remains over which technique of graft fixation should be used, with the option of bony or soft tissue fixation. Cadaveric studies have shown bone plugs to more closely replicate normal meniscal function.58 However, this has not been borne out by human studies, with similar patient outcomes, graft survival, and progression of osteoarthritis in a direct comparison of both types of graft fixation.18 This review identified multiple studies reporting improved function and symptoms in patients receiving either bony fixation or soft tissue fixation. The protagonists for soft tissue fixation argue that it allows more accurate and easier placement of the graft and quicker insertion. Studies have shown good improvement in knee function and symptoms in patients receiving this type of fixation,23,28,33 and histologic comparison of menisci fixed with and without bone plugs has also shown better cellularity, predominant cell types, and collagen organization in nonebone plug grafts.61 Suture-only fixation does lead to greater graft extrusion and although the

13

long-term result of this is unknown, it is a cause for concern. At present, the literature does not clearly support one fixation technique over another. Rehabilitation protocols must strike a balance between maintaining joint motion and muscle strength and protecting the graft to allow full healing of the meniscus and any associated procedures. To achieve this, most authors limit weight bearing and range of motion for up to 6 weeks before progressing activities. Return to contact sports, although controversial, has now been reported with excellent short-term results; however medium- and long-term studies are required before this should be recommended as standard practice. Many of the publications reported patient outcome scores, but there is great variability in which scores were chosen. Although all the scoring systems will give a reasonable approximation of patient pain and function, they need to be validated for use with meniscal transplantation to be truly indicative of the results, and consistent use of the same scoring system would allow results to be compared and meta-analyzed. Meniscal transplant surgeons must reach a consensus over which scoring systems should be reported in the future. There remains a lack of knowledge about the progression of osteoarthritis and longevity of symptom relief after meniscal transplantation, but with time we can expect more long-term follow-up studies to confirm or refute the benefit of MAT. Further research into meniscal transplantation in isolation will help us to truly understand the various issues related to this procedure. The only method to truly determine the benefit of MAT would be a long-term randomized trial versus meniscectomy in symptomatic patients, but with the literature already strongly in favor of MAT, this is unlikely to ever gain ethical approval. The ultimate aims of meniscal transplant are both short termdimprovement in pain and functiondand long termdprevention of onset or progression of joint degeneration. With this in mind, judging success or failure cannot be undertaken simply by analysis of patient outcomes or assessing the viability of the meniscal graft alone. For this reason, we suggest the use of the terms “symptomatic” and “mechanical” failure when reporting MAT results in future studies. Symptomatic failure is defined as patient-reported outcome scores less than or equal to preoperative scores. Mechanical failure is defined as failure of the graft, progression of osteoarthritis, requirement for meniscectomy, or revision transplantation or arthroplasty. Limitations The greatest limitation of this study is a lack of highquality evidence surrounding the art of MAT. Identified articles were often heterogeneous, reporting the use of many different methods of meniscal sizing, fixation techniques, rehabilitation protocols. and outcome

14

P. MYERS AND F. TUDOR

scores, making it impossible to adequately contrast results and outcomes. Despite this, review of the literature has allowed us to identify areas for further research in the field of MAT.

12.

Conclusions MAT is a worthwhile procedure, with evidence that it provides pain relief and improved function, and good results being reported in mid- to long-term studies. The procedure should be considered only in a patient with localized pain and a stable (or stabilized) and wellaligned (or realigned) knee. The controversial areas that were studied in this review include the following: there is no evidence to support either type of fixation, i.e. bone plugs or soft tissues; there is no standardized rehabilitation program, but it appears that full weight bearing by 6 weeks is not detrimental; and a clear and uniform definition of failure and the use of consistent outcome scores would aid future reporting and analysis of the results of meniscal transplantation.

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