The American Journal of Sports Medicine

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1 The American Journal of Sports Medicine Long-term Survivorship and Function of Meniscus Transplantation Frank R. Noyes and Sue D. Barber-Westin Am J Sports Med : 2330 originally published online May 20, 2016 DOI: / The online version of this article can be found at: Published by: On behalf of: American Orthopaedic Society for Sports Medicine Additional services and information for The American Journal of Sports Medicine can be found at: Alerts: Subscriptions: Reprints: Permissions: >> Version of Record - Sep 1, 2016 OnlineFirst Version of Record - May 20, 2016 What is This? Downloaded from ajs.sagepub.com at UNIV OF PITTSBURGH on September 15, 2016

2 Long-term Survivorship and Function of Meniscus Transplantation Frank R. Noyes,* y MD, and Sue D. Barber-Westin, y BS Investigation performed at the Cincinnati Sportsmedicine and Orthopaedic Center Mercy Health, Cincinnati, Ohio, USA Background: Clinical outcomes and survivorship of meniscus transplants remain unclear, especially when magnetic resonance imaging (MRI) and weightbearing radiographic findings are included as endpoints. Many studies calculate survivorship based only on subsequent operative procedures. Purpose: We prospectively determined long-term survivorship and functional outcomes of 72 consecutive meniscus transplants. The effects of articular cartilage damage, concurrent osteochondral autograft transfer (20 knees), patient age, and tibiofemoral compartment were evaluated. Study Design: Case series; Level of evidence, 4. Methods: The long-term function and survival rates of 69 of 72 consecutive medial and lateral bone-meniscus-bone transplants (96% follow-up) were determined. Survival endpoints of reoperations, MRI failure (grade 3 signal intensity, extrusion.50% of meniscal width), meniscal tear on examination, and radiographic loss of joint space provided a worst-case outcome. Longterm functional analysis was performed in 58 transplants a mean of years postoperatively. The Cincinnati and International Knee Documentation Committee rating systems were used to evaluate outcomes. Results: For all transplants, the estimated probability of survival was 85% at 2 years, 77% at 5 years, 69% at 7 years, 45% at 10 years, and 19% at 15 years. There were significant improvements for pain, swelling, walking, stair climbing, and patient knee rating (P \.05). Further surgery was performed in 37 cases. Knees that had concurrent osteochondral autograft transfer had significantly lower survival rates beginning at the seventh postoperative year; however, there was no significant difference in the long-term symptom, function, and patient perception scores between these knees and the rest of the cohort. The factors of articular cartilage damage (grade 2B/3 vs none), patient age (\30 years vs years), and tibiofemoral compartment (medial vs lateral) had no significant effect on the survival, symptom, or functional analyses. Conclusion: A survival analysis that includes reoperations, MRI, radiographs, and a comprehensive examination provides a worst-case but realistic analysis of transplant function. Many patients experienced a short- and long-term benefit of reduced symptoms and improved function. However, meniscus transplants undergo a deleterious remodeling process and eventually fail. Patients should be advised that the procedure is not curative in the long term, and additional surgery will likely be required. Keywords: meniscus; allograft; meniscus transplantation; survivorship Meniscus transplantation has been performed for more than 20 years with the goals of decreasing patient symptoms and providing load-bearing function and chondroprotective effects in younger active patients after meniscectomy. 8 The reported clinical outcomes vary between studies, and few long-term investigations with adequate cohort sizes have been *Address correspondence to Frank R. Noyes, MD, Cincinnati Sportsmedicine Research and Education Foundation, Montgomery Road, 1st Floor, Cincinnati, OH ( sbwestin@csmref.org). y Cincinnati Sportsmedicine and Orthopaedic Center Mercy Health and the Noyes Knee Institute, Cincinnati, Ohio, USA. One or more of the authors has declared the following potential conflict of interest or source of funding: Funding was received from the Jewish Hospital Foundation and the Noyes Knee Institute. The American Journal of Sports Medicine, Vol. 44, No. 9 DOI: / Ó 2016 The Author(s) published to date. 15,41,43,45 Differences in tissue processing, surgical technique, concomitant operative procedures, articular cartilage status, and outcome measurement instruments make comparisons between studies difficult. The survivorship of meniscus transplantation is frequently based on the need for subsequent surgery. However, magnetic resonance imaging (MRI) and weightbearing radiographic findings provide added important information regarding meniscus size, position, and expected function. The primary purpose of this study was to determine the long-term functional outcomes and survivorship rates in a consecutive series of 72 meniscus transplants. In addition, the effects of articular cartilage damage, concurrent osteochondral autograft transfer procedures, patient age, and affected tibiofemoral compartment on these outcomes were determined. Survivorship was determined using a worstcase scenario that included multiple endpoints of reoperation, MRI, radiographic, and knee examination criteria. 2330

3 AJSM Vol. 44, No. 9, 2016 Long-term Survivorship of Meniscus Transplantation 2331 METHODS Patients Institutional review board approval was obtained for this study, and all patients (or their legal guardians) provided signed informed consent. From November 1995 to May 2005, a total of 72 cryopreserved meniscus transplants were implanted into 69 patients (Table 1). Bilateral transplants were performed in 2 patients, and 1 patient underwent a revision lateral meniscus transplant 10 months after the first failed; both operations were included in this study. The indications for meniscus transplantation were prior meniscectomy, age 50 years or younger, pain in the involved compartment, at least 2 mm of retained tibiofemoral joint space on 45 weightbearing posteroanterior (PA) radiographs, no or only minimal bone exposure on tibiofemoral surfaces, and normal axial alignment. Contraindications included advanced arthrosis (flattening of the femoral condyles, concavity of the tibial plateau, and osteophytes that prevented anatomic seating of the transplant), bipolar lesions with bone exposed on both tibia and femur, uncorrected axial malalignment or knee ligament deficiency, arthrofibrosis, prior joint infection, obesity, symptomatic patellofemoral cartilage deterioration, and prophylaxis in asymptomatic patients. Patients with knee ligament deficiency (anterior cruciate ligament [ACL], grade 2 or 3 pivot shift; posterior cruciate ligament [PCL], 10 mm increased posterior tibial displacement; posterolateral ligament deficiency,.10 mm increased lateral joint opening and.15 increased external tibial rotation) who were willing to undergo staged or concurrent ligament reconstruction were considered candidates. Patients with varus osseous lower limb malalignment who were willing to undergo staged high tibial osteotomy (HTO) were also considered for the transplant procedure. Surgical Technique The meniscus transplantation techniques (all performed by F.R.N.) and rehabilitation program followed previous methods. 22,24 Diagnostic arthroscopy performed just before the transplant confirmed the preoperative diagnosis and articular cartilage damage. There was noteworthy articular cartilage damage in the affected tibiofemoral compartment (Cincinnati Knee Rating 2B or 3, 25 indicating extensive fissuring and fragmentation or subchondral bone exposed) documented at the time of transplantation in 51 knees (71%). Bone-meniscus-bone transplants were used in all cases with arthroscopic inside-out techniques. All transplants were obtained from Cryolife; immune response was not assessed. Intraoperative meniscus sizing and use of templated measurements at the time of surgery have been previously described and were important to limit transplant extrusion, which was documented with postoperative MRI and radiographs. 23 Anteroposterior and lateral radiographs were used to obtain approximate width and length TABLE 1 Patient Demographics Meniscus transplants/patients, n 72/69 Mean age (range), y 30 (14-49) Male/female, n 33/36 Left/right knee, n 36/33 Medial/lateral meniscus transplant, n 41/31 Mean time from injury to transplant (range), y 10.3 (0.9-31) Prior operations, n procedures Meniscectomy 117 Meniscus repair 14 Arthroscopy, debridement 53 Anterior cruciate ligament reconstruction 30 Posterior cruciate ligament reconstruction 6 Medial collateral ligament repair 3 Fibular collateral ligament reconstruction 1 Meniscus transplant, irradiated 2 Osteochondral autograft transfer 3 Other 11 measurements for the meniscus transplant (based on tibial plateau measurements), as described by Pollard et al. 26 It is important to note that there is no consensus regarding the best method to determine transplant sizing, and other methods have been investigated to determine these dimensions, including MRI, 7,29 3-dimensional computed tomography, 18 photographs of the transplant, 3 and calculations to predict transplant size based on patient height, weight, and sex. 36 At the time of surgery, adjustments were made to the transplant to allow implantation in the correct anatomic position, without extrusion, as previously described. 23 Thirty-two knees (44%) underwent an isolated meniscus transplant, and 40 (56%) underwent either concurrent or staged operative procedures. Concurrent procedures (see Appendix Table A1, available in the online version of this article and at included 20 osteochondral autograft transfers on the femoral condyle (10 with medial transplants and 10 with lateral transplants), 6 primary knee ligament reconstructions, and 2 revision knee ligament reconstructions. Four patients underwent staged knee ligament reconstructions a mean 6 SD of months before the meniscus transplant (6 ACL and 1 PCL reconstruction). Four other patients underwent staged ACL revision reconstructions a mean of months after the transplant; none of these patients had full giving way during daily activities, and all transplants were fully intact at the time of the ligament reconstruction. Thirteen patients presented with varus osseous lower limb malalignment and underwent staged HTO (8 closing-wedge and 5 openingwedge) a mean of months before the meniscus transplant. One other patient underwent a staged distal femoral opening-wedge osteotomy for valgus malalignment. The postoperative rehabilitation involved protected weightbearing for 6 weeks in a long-leg brace. 24 Range of knee motion exercises from 0 to 90 were begun the first day postoperatively; the range of flexion was increased each week to allow 135 after the fourth week. Muscle strengthening and flexibility exercises were also begun immediately postoperatively and advanced to allow balance, proprioception, and closed kinetic chain exercises at

4 2332 Noyes and Barber-Westin The American Journal of Sports Medicine 6 weeks. Stationary bicycling was allowed at the 8th week and swimming between the 9th and 12th weeks. Light recreational sports were not permitted for at least 12 months, and patients were advised not to return to strenuous highimpact athletics. Clinical Evaluation The follow-up knee examinations included assessment of tibiofemoral joint pain on palpation and during joint motion, palpable meniscus displacement during joint compression and distraction, and rotation and flexion tests (McMurray). 9,17,20 The examination also evaluated the patellofemoral joint, knee stability, and gait abnormalities. The results were rated according to the International Knee Documentation Committee (IKDC) objective evaluation form. The assessment of knee function was performed using the Cincinnati Knee Rating System 2 to determine knee function, symptoms, sports, and occupational activity levels. Patients rated the overall condition of their knee on a scale from 1 to 10 (1-2 = poor, 3-4 = fair, 5-6 = good, 7-8 = very good, and 9-10 = normal). Imaging Evaluation The tibiofemoral joint space was evaluated in all knees before surgery and at follow-up with 45 weightbearing PA radiographs. Axial alignment was measured with full-length hip-knee-ankle standing radiographs in knees that demonstrated varus or valgus malalignment. MRI was performed in all knees preoperatively to determine the status of the articular cartilage and prior meniscectomy. At follow-up, MRI evaluations were routinely performed 1 to 2 years postoperatively or any other time that the surgeon believed that patient symptoms warranted the examination. A subset of 29 transplants underwent research MRIs under full or partial weightbearing conditions a mean of 2.9 years (range, years) postoperatively, as previously described. 22 In these knees, 17 had no transplant midbody extrusion, 11 had minor extrusion (\3 mm), and 1 could not be rated. There was no extrusion of the anterior horn in all but one, and there was no extrusion in the posterior horn in all but one transplant. In all knees, transplant size, extrusion, and signal intensity were determined and failure assigned to those that had major extrusion (.50% of meniscus width), grade 3 signal intensity, or a tear. 22 We used the method described by Stoller et al, 34 in which grade 1 represented a nonarticular focal or globular intrasubstance increased signal; grade 2, a horizontal, linear intrasubstance increased signal that extended from the capsular periphery of the meniscus but did not involve an articular meniscal surface; and grade 3, an area of increased signal intensity that communicated or extended to at least 1 articular surface. Statistical Analysis Kaplan-Meier survivorship analysis was performed by an independent statistician to estimate time-defined probabilities for survival of the meniscus transplants at 2, 5, 7, 10, Factor and 15 years postoperatively. The endpoints were reoperations related to the transplant (transplant removal or revision, total knee arthroplasty, unicompartmental knee arthroplasty, or osteotomy), MRI failure (grade 3 signal intensity or extrusion.50% of the meniscus transplant width), signs of meniscal tear on clinical examination, or loss of joint space in the involved tibiofemoral compartment on 45 weightbearing PA radiographs (IKDC grade D). Comparisons of survivorship and long-term knee function between several subgroups were also made (Table 2). Log-rank tests for equality of survival curves were conducted to compare survivorship analyses between subgroups. The long-term functional data were analyzed with paired and unpaired 2-tailed Student t tests and contingency table analyses. The level of significance was set at P \.05. RESULTS TABLE 2 Meniscus Transplant Subgroup Comparisons a Survivorship Survivorship Subgroup Long-term Function Subgroup Articular cartilage damage b Yes 51 (28 MMT, 23 LMT) 43 (23 MMT, 20 LMT) No 21 (13 MMT, 8 LMT) 15 (9 MMT, 6 LMT) Concurrent osteochondral autograft procedure Yes 20 c 18 No 52 c 40 Age, y \ Tibiofemoral compartment of transplant MMT d LMT d Reoperations required Yes 26 d No 32 d No reoperations required (MRI or radiographic failure criteria) Failed 19 Intact 13 a LMT, lateral meniscus transplant; MMT, medial meniscus transplant; MRI, magnetic resonance imaging. b In the affected tibiofemoral compartment, extensive fissuring and fragmentation (grade 2B) or subchondral bone exposed (grade 3A). c Significant difference (P \.0001). See Appendix Tables A5 and A6 (available online at d Significant differences. See Appendix Table A13 (available online). For all transplants, the estimated probability of survival was 85% at 2 years, 77% at 5 years, 69% at 7 years, 45% at 10 years, and 19% at 15 years (Appendix Table A2, available online). The log-rank tests revealed no significant differences in all of the subgroup analyses shown in Table 2, with the exception of concurrent osteochondral autograft transfer (Figure 1). Knees that did not require this

5 AJSM Vol. 44, No. 9, 2016 Long-term Survivorship of Meniscus Transplantation 2333 TABLE 3 Early and Later Reoperations in 37 Cases Postoperative Time Period, y Operative Procedure No. of Cases Early Transplant removed Transplant revised Total knee arthroplasty 3 Later Transplant removed Transplant revised Osteotomy Total knee arthroplasty Unicompartmental knee arthroplasty 4 Figure 1. There was a statistically significant difference in the estimated survival time probabilities between knees that required a concurrent osteochondral autograft transfer and knees that did not require this procedure (P \.05). 1 Censored (removed, lost to follow-up). examination at 17.3 years after transplantation was entirely normal. Twenty-one other transplants were rated as failed according to MRI or radiographic criteria but did not require furthersurgery(table4).themeantimetofailureforthese cases was years postoperatively, and the mean time to the latest follow-up evaluation was years postoperatively. At follow-up, 15 were participating in light recreational sports activities, and all but 1 had no problems or limitations. The patient perception ratings were fair or poor in 5, good or very good in 12, and normal in 4. Functional Outcome Figure 2. Flowchart of the 72 meniscus transplants entered into the study. See also Tables 3 and 4. p.o., postoperative. concurrent procedure had significantly higher survival probability estimates (P \.05). The life tables for all of the subgroups are shown in online Appendix Tables A3 to A10. Meniscus Transplant Failures and Reoperations Reoperations related to failure of the transplants were performed in 37 cases; 11 of these were done from 0.2 to 3.5 years postoperatively and 26 were done later (Figure 2 and Table 3). The mean time for failure was years for medial transplants and years for lateral transplants. In 1 patient (not shown in Table 3), a repair of a tear in the right lateral meniscus transplant was successfully performed 10 years postoperatively. The latest Three transplants (in 3 patients) were lost to follow-up between 1.2 and 2.7 years postoperatively, and 11 transplants (in 9 patients) failed before 4 years postoperatively and required subsequent operations (Figure 2). This left 58 transplants that were included in the analysis of the long-term functional outcome a mean of years postoperatively. Twenty-six of these failed and required later reoperations; these patients completed the functional evaluation just before their subsequent operation a mean of years postoperatively. Thirty-two transplants did not require further surgery and were evaluated a mean of years postoperatively. For all 58 transplants, statistically significant improvements were found at long-term follow-up for pain, swelling, the patient perception of the overall knee condition, walking, and stair climbing (Table 5). Before the operation, 72% had moderate to severe pain with daily activities; at follow-up, 23% had such pain (Figure 3). The patient ratings of the overall knee condition preoperatively and at long-term follow-up are shown in Figure 4. Before the operation, 78% had given up sports, and the remainder were participating with noteworthy symptoms and limitations. At follow-up, 70% were participating in mostly low-impact recreational activities, 7% were participating in these activities with symptoms, and the remainder were not participating.

6 2334 Noyes and Barber-Westin The American Journal of Sports Medicine TABLE 4 Timing of Failure in 21 Cases That Did Not Require Reoperations a No. of Failures MMT, Years Postoperative LMT, Years Postoperative Failure Factor \ \ MRI Standing PA radiograph MRI and radiograph 1 a LMT, lateral meniscus transplant; MMT, medial meniscus transplant; MRI, magnetic resonance imaging; PA, posteroanterior. TABLE 5 Cincinnati Knee Rating Pain and Function Scores: 58 Transplants With Long-term Follow-up a Score, mean 6 SD Factor Point Scale Preoperative Follow-up P Value b Pain \.0001 Swelling Full giving way NS Patient perception \.0001 Walking \.0001 Stair climbing \.0001 Squatting, kneeling NS Running NS Jumping NS Twisting or turning NS a NS, not significant. b As determined with a paired t test. Figure 3. The pain scale shows the highest level of activity possible without the patient experiencing knee pain. The difference between preoperative and follow-up scores was statistically significant (P \.0001). Mod, moderate; Sev, severe. Figure 4. Distribution of the patients according to their perception of the overall knee condition. The difference between preoperative and follow-up scores was statistically significant (P \.0001).

7 AJSM Vol. 44, No. 9, 2016 Long-term Survivorship of Meniscus Transplantation 2335 There were no significant differences at follow-up in the Cincinnati symptom, function, or patient perception scores between patients who had a concomitant osteochondral autograft transfer and those who did not (Appendix Table A11, available online), between patients younger than 30 years of age and those 30 to 49 years of age, or between patients with articular cartilage damage in the affected tibiofemoral compartment and those without joint damage (Appendix Table A12). Patients who received lateral meniscus transplants had higher scores for walking, stair climbing, and squatting-kneeling compared with those who received medial transplants (Appendix Table A13). Patients who did not require further operations had higher scores for all symptoms, the patient perception scale, walking, and stair climbing compared with those who underwent further surgery (Appendix Table A13). Radiographic Evaluation Radiographic evaluation was conducted in the 58 patients in whom the long-term functional analysis was also completed. There was no change in the IKDC radiographic grade in 23 patients; the ratings were A (normal) in 5 patients, B (mild) in 7 patients, C (moderate) in 7 patients, and D (severe) in 4 patients (1 of whom underwent subsequent knee arthroplasty). In 22 patients, the grade decreased 1 level: from A to B in 2 patients, from B to C in 8 patients, and from C to D in 12 patients (5 of whom underwent subsequent knee arthroplasty). In 13 patients, the grade decreased 2 levels: from A to C in 6 patients and from B to D in 7 patients (3 of whom underwent subsequent knee arthroplasty). Therefore, progression of osteoarthritis as measured on standing PA radiographs was noted in 33 cases (57%), and retention of joint space was noted in 21 cases (36%). Four cases (7%) were rated as D before surgery. There was no significant difference in the mean time to failure for patients in whom the preoperative IKDC radiograph grades were A and B (9.9 years), C (8.5 years), or D (10.8 years). Complications Two patients developed infections postoperatively. In one, an arthroscopy and debridement was performed (with retention of the transplant) 4 weeks postoperatively, and the infection resolved. This patient was last seen 2.7 years postoperatively, at which time the examination was completely normal. The second patient was diagnosed with methicillin-resistant staphylococcus aureus and required debridement and synovectomy at 3 and 5 weeks postoperatively, with graft removal at 8 weeks postoperatively with resolution of the infection. One patient developed early arthrofibrosis that was treated with arthroscopic debridements at 3 and 6 months postoperatively, which restored normal knee motion. This patient was last seen 12 years postoperatively and reported no problems with daily activities; however, the transplant was rated as failed according to MRI criteria. Six patients required manipulation under anesthesia for limitations of knee motion, which were performed 3 to 10 weeks postoperatively. Two of these patients underwent concomitant ligament reconstructions, and 2 others had concomitant osteochondral autograft transfer procedures. All 6 patients achieved normal knee motion. DISCUSSION This study reports the long-term analysis of symptoms and functional limitations and survival rates of 69 of 72 consecutive medial and lateral bone-meniscus-bone transplants (96% follow-up rate). The major purpose was to determine survivorship of the transplants based on multiple endpoints, not just patient symptoms or the need for subsequent major surgery. The transplant survival rates for the entire cohort were 85% at 2 years, 77% at 5 years, 69% at 7 years, 45% at 10 years, and 19% at 15 years. Knees that did not require a concurrent osteochondral autograft transfer had significantly higher survival probability estimates than did those that underwent this concurrent procedure. The factors of articular cartilage damage (grade 2B/3 vs none), patient age (\30 vs years), and affected tibiofemoral compartment (medial vs lateral) had no significant effect on the survival rates or analyses of symptoms and functional limitations. Long-term survivorship probability estimates of meniscus transplants have been reported by others. 15,21,35,37,41,42,46 It is difficult to compare studies because of differences in graft processing and fixation, concomitant or staged operative procedures, knee rating systems, and endpoints chosen for survival. Our previous 21 and current studies used multiple endpoints of not only major reoperations but also MRI, clinical examination, and standing PA radiographs to define failure as a worst-case analysis. We included MRI and radiographic criteria as endpoints because we question whether transplants that are extruded more than 50% of the meniscus width or have a grade 3 signal alteration are functional, as well as those that are in knees with no remaining joint space in the affected tibiofemoral compartment. In addition, it is well known clinically that knees with advanced arthrosis and loss of a meniscus may undergo successful nonoperative treatment for years before requiring operative intervention. In our study, 21 transplants were rated as failed according to MRI or radiographic criteria; however, 16 of these patients rated their knee condition as good to normal a mean of years postoperatively. In our opinion, the use of the reoperation rate alone to determine survivorship may result in a major positive bias. If MRI and radiographic criteria endpoints had not been included in our study, the estimated probability of transplant survival rates would have increased to 90% at 2 years, 84% at 5 years, 79% at 7 years, 64% at 10 years, and 50% at 15 years. Other investigations that used only knee arthroplasty and/or transplant removal reported 10-year survival rates of 85%, 46 55%, 35 and 52.5%. 41 The ability to simultaneously perform articular cartilage procedures with meniscus transplantation has expanded the indications for this operation. 31 Rue et al 32 reported the initial outcomes of 31 patients who underwent meniscus transplants (cryopreserved or fresh-frozen) combined with

8 2336 Noyes and Barber-Westin The American Journal of Sports Medicine Figure 5. A medial meniscus transplant in a right knee at the latest follow-up evaluation, 14.3 years postoperative. This male patient was 41 years old at the time of surgery. (A) Radiograph shows good retention of the joint space. (B) Coronal and (C) sagittal MRI views show a small cyst adjacent to the medial collateral ligament and a decrease in transplant size. The patient rated the overall condition of his knee as very good and was asymptomatic with recreational activities. MRI, magnetic resonance imaging. either osteochondral allografts (15) or autologous chondrocyte implantation (16). At a mean of 3.1 years postoperatively, the group as a whole showed significant improvements in Lysholm, Tegner, Cincinnati, IKDC, Knee injury and Osteoarthritis Outcome, and Short Form 12 scores. In our cohort, at a mean of 10.7 years postoperatively, 18 patients who had a concurrent osteochondral autograft transfer had significant improvements in the scores for pain, patient perception of the knee condition, and walking (P \.001). In this subgroup of complex knees, 6 patients had other operative procedures, including a knee ligament reconstruction (3 patients), a staged HTO (2 patients), and a staged HTO and a knee ligament reconstruction (1 patient). There was a significant decline in survival rates beginning at the seventh postoperative year between knees that received an osteochondral autograft transfer and the rest of the cohort. It is important to note that, in the osteochondral autograft subgroup, 8 of the 17 knees in whom the transplant was rated as failed received this rating based on MRI, radiographic, or clinical examination findings. At the time of the final follow-up, 5 in this subgroup had undergone knee arthroplasty, 2 had undergone osteotomy, 2 had the transplant revised, and 3 had the transplant removed. Thirteen patients presented to our center with varus osseous lower limb malalignment after medial meniscectomy. Untreated lower limb malalignment has been associated with failed meniscus transplantation in historical studies. 6,39 For instance, van Arkel and de Boer 39 noted uncorrected varus or valgus malalignment in 8 of 23 patients resulted in poorer Lysholm scores (mean, 65 points) compared with those of patients with neutral alignment (mean, 81 points) a mean of 3 years postoperatively. Therefore, osteotomy is frequently performed either staged or with meniscal transplantation. z In our study, all 13 patients recovered fully from the osteotomy, but medial compartment symptoms continued that necessitated the transplants that z References 1, 4, 5, 10, 11, 14, 16, 19, 35, 38, 43. were done an average of 1 year later (range, 4-23 months). Five of these 13 patients required other procedures with the transplant of either osteochondral autograft transfer (3 patients) or ACL reconstructions (3 patients). The estimated probability of transplant survival for these 13 cases was 85% at 2 years, 54% at 5 years, 46% at 7 years, 38% at 10 years, and 15% at 15 years. The limited number of patients in this subgroup does not allow for definitive conclusions. Kazi et al 16 performed meniscus transplantation in 86 cases, 27 of which were done in conjunction with HTO. There was no difference in the median survival times between the combined cases and those done without HTO. Overall, 15 transplants were debrided a mean of 5.6 years postoperatively, and 24 had a total knee arthroplasty a mean of 12.4 years postoperatively. It is unknown how many of these 39 cases underwent a concomitant HTO. Verdonk et al 43 reported on 42 meniscus transplant cases, 11 of which were done with an HTO. Two of these 11 went on to total knee arthroplasty a mean of 6.5 years postoperatively. Seventeen patients in our study had chronic knee ligament deficiency that required a concurrent or staged reconstruction. Uncorrected knee joint instability has been associated with poor clinical outcomes after meniscus transplantation, 40 and these 17 patients had giving-way symptoms with activities. Eight represented revision ligament reconstructions. Four patients underwent HTO first. The survival of these transplants was encouraging; the estimated probability rates were 88% at 2, 5, and 7 years; 61% at 10 years; and 20% at 15 years. Simultaneous ACL reconstruction and meniscus transplantation has been reported by many other investigators. 15,30,33 A systematic review of 55 studies by Rosso et al 31 reported 334 associated ACL reconstructions were done in 1623 patients. We implanted 32 transplants (44%) in patients 30 years of age or younger and 40 transplants (55%) in patients aged 30 to 49 years (Figure 5). There were no significant differences between these 2 subgroups in the estimated probability of transplant survival rates or in any of the functional analyses. This demonstrates that age alone

9 AJSM Vol. 44, No. 9, 2016 Long-term Survivorship of Meniscus Transplantation 2337 (\50 years) should not be an inclusionary or exclusionary criterion in the appropriately indicated patient. There were no significant differences in the estimated probability of transplant survival rates or in the functional outcomes between patients with articular cartilage damage in the involved tibiofemoral compartment and those without joint damage We note that no transplants were used in knees that had advanced arthrosis as indicated by flattening of the femoral condyles, concavity of the tibial plateau, and osteophytes that would prevent anatomic seating of the transplant. A limitation of this study is the use of cryopreserved meniscus transplants and the inability to directly compare the results with those of fresh-frozen transplants. However, there exists a question of whether viable meniscal chondrocytes survive either cryopreservation (done with an agent, dimethyl sulfoxide) or deep-freezing procedures. Investigational studies have demonstrated significant differences in mean cellularity between fresh human menisci (retrieved from knee arthroplasty patients) and cryopreserved menisci of cells and cells, respectively, 44 and wide variability in the percentage of cell survival in cryopreserved menisci (4%-54%). 13 In a study that ascertained the effects of freezing on meniscus collagen architecture, Gelber et al 12 reported significant decreases in fibril collagen diameter and a higher degree of deleterious architectural changes in frozen human menisci compared with control specimens. CONCLUSION Meniscus transplantation is recommended after total meniscectomy in symptomatic patients younger than 50 years in whom articular cartilage deterioration is demonstrated either at arthroscopy or through MRI. 27,28 In patients in whom prior operations failed to alleviate tibiofemoral compartment symptoms, limited options exist. It is important to note that the majority (if not all) meniscus transplants will undergo a deleterious remodeling process at different time periods postoperatively, resulting in altered mechanical properties and eventual failure. In this study, continued radiographic progression of joint deterioration was detected in 57% of the 58 patients who completed the long-term functional analysis. Patients should be advised that the procedure is not curative in the long-term and that the goal is to buy time before further major surgery is required. 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