Evaluation of muscle size and fatty infiltration with MRI nine to eleven years following hamstring harvest for ACL reconstruction.

BACKGROUND: The long-term effect of hamstring tendon harvest for anterior cruciate ligament (ACL) reconstruction on muscle morphology is not well documented. Our hypothesis was that harvest of the hamstring tendons for ACL reconstruction would result in persistent loss of volume and cross-sectional area of the gracilis and semitendinosus muscles. METHODS: Magnetic resonance images were made of both limbs of ten patients nine to eleven years after they had ACL reconstruction with ipsilateral hamstring autograft. The volume of the individual thigh muscles bilaterally was calculated. The peak cross-sectional area and the cross-sectional area 7 cm proximal to the joint line was measured for the gracilis and semitendinosus muscles. Data were evaluated with use of the paired t test and Wilcoxon signed-rank test. The gracilis and semitendinosus muscles on the operatively treated side were evaluated for fatty infiltration and tendon regeneration. RESULTS: The mean volume on the operatively treated side was 54.2% of that on the noninvolved side for the gracilis muscle and 58.5% for the semitendinosus muscle. A 7% decrease in quadriceps volume and an 8% increase in the volume of the long head of the biceps on the operatively treated extremity were noted. The semimembranosus muscle and short head of the biceps muscle showed no difference in volume. The gracilis and semitendinosus muscles also showed a decrease in peak cross-sectional area, a decrease in the cross-sectional area 7 cm proximal to the joint line, and evidence of fatty infiltration. There was variable evidence of tendon or scar formation within the tendon bed, with most patients having some tissue that blended into either the sartorius muscle or medial gastrocnemius fascia at a level proximal to the joint line. CONCLUSIONS: At nine to eleven years after ACL reconstruction with ipsilateral hamstring autograft, the gracilis and semitendinosus muscles showed persistent atrophy on the operatively treated side with evidence of fatty infiltration and variability in tendon regeneration. There was also persistent atrophy of the quadriceps muscles and compensatory hypertrophy of the long head of the biceps. LEVEL OF EVIDENCE: Therapeutic Level IV. See Instructions for Authors for a complete description of levels of evidence.

Does landmark selection affect the reliability of tibial tubercle-trochlear groove measurements using MRI?

BACKGROUND: A lateralized tibial tubercle is one potential cause of patellar instability. The tibial tubercle-trochlear groove (TT-TG) distance using CT is a reliable measure and considered the gold standard. Using MRI for this purpose has increased, although the reliability of doing so is not well studied. QUESTIONS/PURPOSES: We sought to (1) determine variability in the insertion of the patellar tendon relative to the tibial tubercle and whether this affects the measurement on MRI of the traditional TT-TG distance versus the functional patellar tendon-trochlear groove (PT-TG) distance, (2) determine the reliability of measuring the osseous TT-TG distance, (3) determine the reliability of measuring the soft tissue PT-TG distance, and (4) compare the reliabilities of using osseous (TT-TG) versus soft tissue (PT-TG) landmarks. METHODS: Four observers measured the TT-TG and the PT-TG distances of 50 MR images of knees obtained for any reason. Each observer repeated these measurements 30 days later. The interobserver and intraobserver reliabilities, measurements per observer that varied from the group mean by greater than 2 mm, and the limit of agreement were calculated. RESULTS: The TT-TG and PT-TG differed by as little as 0.11 mm and by as much as 4.18 mm with an average difference of 1.37 mm. The interobserver and intraobserver reliabilities were greater than 90% for the PT-TG and TT-TG distances. The PT-TG distance was less variable in that this measurement showed interobserver and intraobserver reliabilities of 0.977 and 0.972 respectively, versus 0.913 and 0.961 for the TT-TG measurement. Additionally, the PT-TG measurements resulted in a lower average difference to the mean for each observer, less number of knees per observer where the difference to the mean was greater than 2 mm, and improved limit of agreement. CONCLUSIONS: The TT-TG and the PT-TG distances were not identical and differed by as much as 4.18 mm; as such they are not interchangeable when measuring this distance. Both methods are reliable for measuring lateral offset of the extensor mechanism, but the use of soft tissue landmarks is less variable and thus would provide a more reliable measurement for surgical planning. LEVEL OF EVIDENCE: Level III, diagnostic study. See the Guidelines for Authors for a complete description of levels of evidence.

EWS/FLI1 suppresses retinoblastoma protein function and senescence in Ewing's sarcoma cells.

Ewing's Family Tumors (EFTs) most commonly harbor a specific t(11;22) translocation that generates the EWS/FLI1 fusion protein responsible for malignant transformation. Many potential downstream targets of EWS/FLI1 have been identified but a detailed mechanism by which the fusion protein brings about transformation remains unknown. In this report, we show that depletion of EWS/FLI1 in Ewing's cell lines results in a senescence phenotype, a marked increase in expression of the G1/S regulatory proteins p27(kip1) and p57(kip2), and a significant decrease in cyclin D1 and CDK2. We also demonstrate for the first time, to our knowledge, that knockdown of EWS/FLI1 leads to hypophosphorylation and functional activation of the retinoblastoma (pRb) family of proteins. Consistent with activation of the pRb proteins, E2F-responsive genes such as cyclin A are repressed in EWS/FLI1-depleted cells. Together, these results support the role of EWS/LI1 as an inhibitor of cellular senescence and implicate the retinoblastoma family of proteins as key mediators of this inhibition.