Can a Liquid Biopsy Detect Circulating Tumor DNA With Low-passage Whole-genome Sequencing in Patients With a Sarcoma? A Pilot Evaluation.

BACKGROUND: A liquid biopsy is a test that evaluates the status of a disease by analyzing a sample of bodily fluid, most commonly blood. In recent years, there has been progress in the development and clinical application of liquid biopsy methods to identify blood-based, tumor-specific biomarkers for many cancer types. However, the implementation of these technologies to aid in the treatment of patients who have a sarcoma remains behind other fields of cancer medicine. For this study, we chose to evaluate a sarcoma liquid biopsy based on circulating tumor DNA (ctDNA). All human beings have normal cell-free DNA (cfDNA) circulating in the blood. In contrast with cfDNA, ctDNA is genetic material present in the blood stream that is derived from a tumor. ctDNA carries the unique genomic fingerprint of the tumor with changes that are not present in normal circulating cfDNA. A successful ctDNA liquid biopsy must be able to target these tumor-specific genetic alterations. For instance, epidermal growth factor receptor (EGFR) mutations are common in lung cancers, and ctDNA liquid biopsies are currently in clinical use to evaluate the status of disease in patients who have a lung cancer by detecting EGFR mutations in the blood. As opposed to many carcinomas, sarcomas do not have common recurrent mutations that could serve as the foundation to a ctDNA liquid biopsy. However, many sarcomas have structural changes to their chromosomes, including gains and losses of portions or entire chromosomes, known as copy number alterations (CNAs), that could serve as a target for a ctDNA liquid biopsy. Murine double minute 2 (MDM2) amplification in select lipomatous tumors or parosteal osteosarcoma is an example of a CNA due to the presence of extra copies of a segment of the long arm of chromosome 12. Since a majority of sarcomas demonstrate a complex karyotype with numerous CNAs, a blood-based liquid biopsy strategy that searches for these CNAs may be able to detect the presence of sarcoma ctDNA. Whole-genome sequencing (WGS) is a next-generation sequencing technique that evaluates the entire genome. The depth of coverage of WGS refers to how detailed the sequencing is, like higher versus lower power on a microscope. WGS can be performed with high-depth sequencing (that is, > 60×), which can detect individual point mutations, or low-depth sequencing (that is, 0.1× to 5×), referred to as low-passage whole-genome sequencing (LP-WGS), which may not detect individual mutations but can detect structural chromosomal changes including gains and losses (that is, CNAs). While similar strategies have shown favorable early results for specific sarcoma subtypes, LP-WGS has not been evaluated for applicability to the broader population of patients who have a sarcoma. QUESTIONS/PURPOSES: Does an LP-WGS liquid biopsy evaluating for CNAs detect ctDNA in plasma samples from patients who have sarcomas representing a variety of histologic subtypes? METHODS: This was a retrospective study conducted at a community-based, tertiary referral center. Nine paired (plasma and formalin-fixed paraffin-embedded [FFPE] tissue) and four unpaired (plasma) specimens from patients who had a sarcoma were obtained from a commercial biospecimen bank. Three control specimens from individuals who did not have cancer were also obtained. The paired and unpaired specimens from patients who had a sarcoma represented a variety of sarcoma histologic subtypes. cfDNA was extracted, amplified, and quantified. Libraries were prepared, and LP-WGS was performed using a NextSeq 500 next-generation sequencing machine at a low depth of sequencing coverage (∼1×). The ichorCNA bioinformatics algorithm, which was designed to detect CNAs from low-depth genomic sequencing data, was used to analyze the data. In contrast with the gold standard for diagnosis in the form of histopathologic analysis of a tissue sample, this test does not discriminate between sarcoma subtypes but detects the presence of tumor-derived CNAs within the ctDNA in the blood that should not be present in a patient who does not have cancer. The liquid biopsy was positive for the detection of cancer if the ichorCNA algorithm detected the presence of ctDNA. The algorithm was also used to quantitatively estimate the percent ctDNA within the cfDNA. The concentration of ctDNA was then calculated from the percent ctDNA relative to the total concentration of cfDNA. The CNAs of the paired FFPE tissue and plasma samples were graphically visualized using aCNViewer software. RESULTS: This LP-WGS liquid biopsy detected ctDNA in 9 of 13 of the plasma specimens from patients with a sarcoma. The other four samples from patients with a sarcoma and all serum specimens from patients without cancer had no detectable ctDNA. Of those 9 patients with positive liquid biopsy results, the percent ctDNA ranged from 6% to 11%, and calculated ctDNA quantities were 0.04 to 5.6 ng/mL, which are levels to be expected when ctDNA is detectable. CONCLUSION: In this small pilot study, we were able to detect sarcoma ctDNA with an LP-WGS liquid biopsy searching for CNAs in the plasma of most patients who had a sarcoma representing a variety of histologic subtypes. CLINICAL RELEVANCE: These results suggest that an LP-WGS liquid biopsy evaluating for CNAs to identify ctDNA may be more broadly applicable to the population of patients who have a sarcoma than previously reported in studies focusing on specific subtypes. Large prospective clinical trials that gather samples at multiple time points during the process of diagnosis, treatment, and surveillance will be needed to further assess whether this technique can be clinically useful. At our institution, we are in the process of developing a large prospective clinical trial for this purpose.

Extremity Soft Tissue Sarcoma: A Multi-Institutional Validation of Prognostic Nomograms.

BACKGROUND: Prognostic nomograms for patients with resected extremity soft tissue sarcoma (STS) include the Sarculator and Memorial Sloan Kettering (MSKCC) nomograms. We sought to validate these two nomograms within a large, modern, multi-institutional cohort of resected primary extremity STS patients. METHODS: Resected primary extremity STS patients from 2000 to 2017 were identified across nine high-volume U.S. institutions. Predicted 5- and 10-year overall survival (OS) and distant metastases cumulative incidence (DMCI), and 4-, 8-, and 12-year disease-specific survival (DSS) were calculated with Sarculator and MSKCC nomograms, respectively. Predicted survival probabilities stratified in quintiles were compared in calibration plots to observed survival assessed by Kaplan-Meier estimates. Cumulative incidence was estimated for DMCI. Harrell's concordance index (C-index) assessed discriminative ability of nomograms. RESULTS: A total of 1326 patients underwent resection of primary extremity STS. Common histologies included: undifferentiated pleomorphic sarcoma (35%), fibrosarcoma (13%), and leiomyosarcoma (9%). Median tumor size was 8.0 cm (IQR 4.5-13.0). Tumor grade distribution was: Grade 1 (13%), Grade 2 (9%), Grade 3 (78%). Median OS was 172 months, with estimated 5- and 10-year OS of 70% and 58%. C-indices for 5- and 10-year OS (Sarculator) were 0.72 (95% CI 0.70-0.75) and 0.73 (95% CI 0.70-0.75), and 0.72 (95% CI 0.69-0.75) for 5- and 10-year DMCI. C-indices for 4-, 8-, and 12-year DSS (MSKCC) were 0.71 (95% CI 0.68-0.75). Calibration plots showed good prognostication across all outcomes. CONCLUSIONS: Sarculator and MSKCC nomograms demonstrated good prognostic ability for survival and recurrence outcomes in a modern, multi-institutional validation cohort of resected primary extremity STS patients. External validation of these nomograms supports their ongoing incorporation into clinical practice.

A multi-institutional validation study of prognostic nomograms for retroperitoneal sarcoma.

BACKGROUND AND OBJECTIVES: Prognostic nomograms for patients undergoing resection of retroperitoneal sarcoma (RPS) include the Sarculator and Memorial Sloan Kettering (MSK) sarcoma nomograms. We sought to validate the Sarculator and MSK nomograms within a large, modern multi-institutional cohort of patients with primary RPS undergoing resection. METHODS: Patients who underwent resection of primary RPS between 2000 and 2017 across nine high-volume US institutions were identified. Predicted 7-year disease-free (DFS) and overall survival (OS) and 4-, 8-, and 12-year disease-specific survival (DSS) were calculated from the Sarculator and MSK nomograms, respectively. Nomogram-predicted survival probabilities were stratified in quintiles and compared in calibration plots to observed survival outcomes assessed by Kaplan-Meier estimates. Discriminative ability of nomograms was quantified by Harrell's concordance index (C-index). RESULTS: Five hundred and two patients underwent resection of primary RPS. Histologies included leiomyosarcoma (30%), dedifferentiated liposarcoma (23%), and well-differentiated liposarcoma (15%). Median tumor size was 14.0 cm (interquartile range [IQR], 8.5-21.0 cm). Tumor grade distribution was: Grade 1 (27%), Grade 2 (17%), and Grade 3 (56%). Median DFS was 31.5 months; 7-year DFS was 29%. Median OS was 93.8 months; 7-year OS was 51%. C-indices for 7-year DFS, and OS by the Sarculator nomogram were 0.65 (95% confidence interval [CI]: 0.62-0.69) and 0.69 (95%CI: 0.65-0.73); plots demonstrated good calibration for predicting 7-year outcomes. The C-index for 4-, 8-, and 12-year DSS by the MSK nomogram was 0.71 (95%CI: 0.67-0.75); plots demonstrated similarly good calibration ability. CONCLUSIONS: In a diverse, modern validation cohort of patients with resected primary RPS, both Sarculator and MSK nomograms demonstrated good prognostic ability, supporting their ongoing adoption into clinical practice.

Genomic alterations and clinical outcomes in patients with dedifferentiated liposarcoma.

PURPOSE: Patients with unresectable dedifferentiated liposarcoma (DDLPS) have poor overall outcomes. Few genomic alterations have been identified with limited therapeutic options. EXPERIMENTAL DESIGN: Patients treated at Levine Cancer Institute with DDLPS were identified. Next generation sequencing (NGS), immunohistochemistry (IHC), and fluorescence in situ hybridization (FISH) testing were performed on tumor tissue collected at diagnosis or recurrence/progression. Confirmation of genomic alterations was performed by orthologous methods and correlated with clinical outcomes. Univariate Cox regression was used to identify genomic alterations associated with clinical outcomes. RESULTS: Thirty-eight DDLPS patients with adequate tissue for genomic profiling and clinical data were identified. Patient characteristics included: median age at diagnosis (66 years), race (84.2% Caucasian), and median follow-up time for the entire cohort was 12.1 years with a range from approximately 3.5 months to 14.1 years. Genes involved in cell cycle regulation, including MDM2 (74%) CDK4 (65%), and CDKN2A (23%), were amplified along with WNT/Notch pathway markers: HMGA2, LGR5, MCL1, and CALR (19%-29%). While common gene mutations were identified, PDE4DIP and FOXO3 were also mutated in 47% and 34% of patients, respectively, neither of which have been previously reported. FOXO3 was associated with improved overall survival (OS) (HR 0.37; p = 0.043) along with MAML2 (HR 0.30; p = 0.040). Mutations that portended worse prognosis included RECQL4 (disease-specific survival HR 4.67; p = 0.007), MN1 (OS HR = 3.38; p = 0.013), NOTCH1 (OS HR 2.28, p = 0.086), and CNTRL (OS HR 2.42; p = 0.090). CONCLUSIONS: This is one of the largest retrospective reports analyzing genomic aberrations in relation to clinical outcomes for patients with DDLPS. Our results suggest therapies targeting abnormalities should be explored and confirmation of prognostic markers is needed. Dedifferentiated liposarcoma is one of the most common subtypes of soft tissue sarcoma yet little is known of its molecular aberrations and possible impact on outcomes. The work presented here is an evaluation of genetic abnormalities among a population of patients with dedifferentiated liposarcoma and how they corresponded with survival and risk of metastases. There were notable gene mutations and amplifications commonly found, some of which had interesting prognostic implications.

Evaluation of a simulated pivot shift test: a biomechanical study.

PURPOSE: Double-bundle anterior cruciate reconstructions have led to an increased interest in quantifying anterolateral rotatory stability. The application of combined internal rotation and valgus torques to the knee can more nearly recreate the anterolateral subluxation that occurs in the pivot shift test in vitro compared to coupled internal rotation torque and anterior tibial loads. METHODS: Twelve non-paired cadaveric knees were biomechanically tested with the ACL intact and sectioned. For each test state, six-degree-of-freedom positional data were collected for two simulated pivot shift loads consisting of a 5-Nm internal rotation torque coupled with either a 10-Nm valgus torque or an 88 N anterior tibial load at 0°, 20°, 30°, 60°, and 90° of knee flexion. RESULTS: The coupled internal rotation and valgus torques produced a significant increase in anterolateral subluxation between the ACL intact and sectioned states at all tested angles except 90º (5.9 ± 0.4 mm at 0°, 4.3 ± 0.6 mm at 20°, 3.5 ± 0.6 mm at 30°, 2.1 ± 0.6 mm at 60°). The coupled internal rotation and an anterior tibial load produced significant increases between the ACL intact and sectioned states at all tested angles except 30º (5.4 ± 0.5 mm at 0°, 3.7 ± 0.5 mm at 20°, 2.1 ± 0.8 mm at 60°, 1.4 ± 0.3 mm at 90°). CONCLUSIONS: We found that the coupled internal rotation and valgus torques best recreated the anterolateral subluxation that occurs in the pivot shift in vitro. This study describes an anterolateral subluxation test for ACL integrity in the laboratory setting.

Radiographic landmarks for tunnel positioning in double-bundle ACL reconstructions.

PURPOSE: The purpose of this study was to establish quantitative and qualitative radiographic landmarks for identifying the femoral and tibial attachment sites of the AM and PL bundles of the native ACL and to assess the reproducibility of identification of these landmarks using intraclass correlation coefficients. It was hypothesized that the radiographic positions of the AM and PL bundles could be defined in relation to anatomic landmarks and radiographic reference lines. METHODS: The femoral and tibial attachment sites of the AM and PL bundles on twelve cadaveric knees were labeled with radio-opaque markers. The positions of the AM and PL bundle attachment sites were quantified on radiographs by three independent examiners. RESULTS: On the lateral femoral view, the AM bundle was located at 21.6 ± 5.6% of the sagittal diameter of the femur drawn along Blumensaat's line and 14.2 ± 7.7% distal to the notch roof along the maximum notch height. The PL bundle was located at 28.9 ± 4.6% of the sagittal diameter and 42.3 ± 6.0% of the notch height. The knee flexion angle at which the AM and PL bundle attachment sites were horizontally oriented was 115 ± 7.1°. On the tibial AP view, the AM and PL bundles were located at 44.2 ± 3.4 and 50.1 ± 2.1%, respectively, from the medial aspect of the tibia along its coronal diameter. On the lateral view, the distances from the AM and PL bundles to the anterior tibial margin measured along the tibial sagittal diameter were 36.3 ± 3.8 and 51.0 ± 4.0%, respectively. The center of the PL bundle attachment was located almost precisely at the center of the tibial plateau in both the coronal and sagittal planes. CONCLUSIONS: This study defines the radiographic locations of the femoral and tibial bundle attachment sites of the native ACL and a reliable and transferrable protocol for identifying these sites on radiographs in relation to surrounding landmarks and digitally projected reference lines. In addition, it was found that the femoral attachments of the AM and PL bundles were horizontally aligned at 115° of knee flexion and the PL bundle tibial attachment was located essentially at the center of the tibia.

Survival and NF1 Analysis in a Cohort of Orthopedics Patients with Malignant Peripheral Nerve Sheath Tumors.

Neurofibromatosis type 1 (NF1) is an autosomal dominant tumor syndrome in which benign plexiform neurofibromas are at risk of transforming into malignant peripheral nerve sheath tumors (MPNSTs), a very rare soft-tissue sarcoma. The prognosis of patients with MPNSTs is poor, with most studies reporting <50% survival at five years. However, studies evaluating MPNSTs are limited and report heterogeneous results. Because no MPNST-specific evidence-based treatment guideline exists, individual institutional experiences are very informative to the field. The main objective of this study was to investigate and report MPNST prognostic clinical and genetic biomarkers from our institution's Orthopedics service experience treating 20 cases from 1992 to 2017. Most patients were treated with resection and adjuvant radiation. Extended follow-up, averaging 11.4 years (ranging 1.1 to 25.1), revealed excellent five-year survival rates: 70% for overall and 60% for metastatic disease. An S100 B immunonegative tumor phenotype was associated with a significantly worse outcome than MPNSTs with positive S100 B stain. In addition, NF1 gene mutation analysis was performed on 27 families with NF1 in which at least one affected family member developed MPNSTs. Of the 27 NF1 germline mutations, five were large deletions spanning (or nearly spanning) the gene (18.5%), substantially more than such deletions in NF1 in general, consistent with increased risk of MPNSTs in such cases.

Phase II Study of Pembrolizumab in Combination with Doxorubicin in Metastatic and Unresectable Soft-Tissue Sarcoma.

PURPOSE: Doxorubicin is standard therapy for advanced soft-tissue sarcoma (STS) with minimal improvement in efficacy and increased toxicity with addition of other cytotoxic agents. Pembrolizumab monotherapy has demonstrated modest activity and tolerability in previous advanced STS studies. This study combined pembrolizumab with doxorubicin to assess safety and efficacy in frontline and relapsed settings of advanced STS. PATIENTS AND METHODS: This single-center, single-arm, phase II trial enrolled patients with unresectable or metastatic STS with no prior anthracycline therapy. Patients received pembrolizumab 200 mg i.v. and doxorubicin (60 mg/m2 cycle 1 with subsequent escalation to 75 mg/m2 as tolerated). The primary endpoint was safety. Secondary endpoints included overall survival (OS), objective response rate (ORR), and progression-free survival (PFS) based on RECIST v1.1 guidelines. RESULTS: Thirty patients were enrolled (53.3% female; median age 61.5 years; 87% previously untreated) with 4 (13.3%) patients continuing treatment. The study met its primary safety endpoint by prespecified Bayesian stopping rules. The majority of grade 3+ treatment-emergent adverse events were hematologic (36.7% 3+ neutropenia). ORR was 36.7% [95% confidence interval (CI), 19.9-56.1%], with documented disease control in 80.0% (95% CI, 61.4-92.3%) of patients. Ten (33.3%) patients achieved partial response, 1 (3.3%) patient achieved complete response, and 13 (43.3%) patients had stable disease. Median PFS and OS were 5.7 months (6-month PFS rate: 44%) and 17 months (12-month OS rate: 62%), respectively. Programmed cell death ligand-1 (PD-L1) expression was associated with improved ORR, but not OS or PFS. CONCLUSIONS: Combination pembrolizumab and doxorubicin has manageable toxicity and preliminary promising activity in treatment of patients with anthracycline-naive advanced STS.

Clinical Care Guideline for Improving Pediatric Acute Musculoskeletal Infection Outcomes.

BACKGROUND: Acute pediatric musculoskeletal infections are common, leading to significant use of resources and antimicrobial exposure. In order to decrease variability and improve the quality of care, Children's Hospital Colorado implemented a clinical care guideline (CCG) for these infections. The purpose of this study is to evaluate clinical and resource outcomes PRE and POST this CCG. METHODS: Retrospective chart review evaluated patients admitted to a large pediatric quaternary referral center (CHCO) diagnosed with acute osteomyelitis, septic arthritis, pyomyositis, and/or musculoskeletal abscess prior to and after guideline implementation. Primary outcomes included length of stay and overall antibiotic use, with additional secondary clinical, process, and therapeutic outcomes examined. RESULTS: 82 patients were identified in both the pre-CCG and post-CCG cohorts. There was a reduction in the median of all primary outcomes, including length of stay (0.6 median days decrease, P = .04), length of IV antibiotic therapy (4.9 median days decrease, P < .0001), and days of IV antibiotic therapy (6.4 median days decrease, P = .0004). Our median length of stay post-CCG was 4.9 days, the shortest reported length of stay for pediatric acute musculoskeletal infections to date. Additionally, there was a 24.5 hour reduction in median length of fever (P = .02), faster CRP normalization (P < .0001), 50% decrease in the number of related readmissions (P = .02), 34% decrease in central venous catheters placed (P < .0001), decreased time to first culture (P = .02), and 79% pathogen identification post-CCG (P = .056). CONCLUSIONS: Implementation of a CCG for acute musculoskeletal infections improves patient, process and resource outcomes.

A technique for pediatric chest wall reconstruction using custom-designed titanium implants: description of technique and report of two cases.

PURPOSE: We present a surgical technique for chest wall reconstruction using custom-designed titanium implants developed for two female patients to provide both chest wall symmetry and adequate stability for staged breast reconstruction. METHODS: A retrospective review was performed for two adolescent female patients with large chest wall defects who underwent the described technique. The etiology of the chest wall deficiency was secondary to Poland's syndrome in one patient, and secondary to surgical resection of osteosarcoma in the other patient. For each patient, a fine-cut computed tomography scan was obtained to assist with implant design. After fabrication of the prosthesis, reconstruction was performed though a curvilinear thoracotomy approach with attachment of the implant to the adjacent ribs and sternum. Wound closure was obtained with use of synthetic graft material, local soft tissue procedures, and flap procedures as necessary. RESULTS: The two patients were followed post-operatively for 35 and 38 months, respectively. No intra-operative or post-operative complications were identified. Mild scoliosis that had developed in the patient following chest wall resection for osteosarcoma did not demonstrate any further progression following reconstruction. CONCLUSIONS: We conclude that this technique was successful at providing a stable chest wall reconstruction with satisfactory cosmetic results in our patients.

Radiographic landmarks for tunnel positioning in posterior cruciate ligament reconstructions.

BACKGROUND: Consistent radiographic guidelines for tunnel placement in single- or double-bundle posterior cruciate ligament (PCL) reconstructions are not well defined. Quantitative guidelines reporting the location of the individual PCL bundle attachments would aid in intraoperative tunnel placement and postoperative assessment of a PCL reconstruction. HYPOTHESIS: Consistent and reproducible measurements in relation to radiographic landmarks for the entire PCL and its individual bundle attachments are achievable. STUDY DESIGN: Controlled laboratory study. METHODS: The femoral and tibial PCL bundle attachment centers of 20 nonpaired fresh-frozen cadaveric knees were labeled using radio-opaque spheres and the attachment areas were labeled using barium sulfate. Anteroposterior (AP) and lateral radiographs of the femur and tibia were obtained, and measurements of the distances between the PCL bundle centers and landmarks were acquired. RESULTS: On the AP femur view, the anterolateral bundle (ALB) and posteromedial bundle (PMB) centers were 34.1 ± 3.0 mm and 29.2 ± 3.0 mm lateral to the most medial border of the medial femoral condyle, respectively. The lateral femur images revealed that the ALB center was 17.4 ± 1.7 mm and the PMB center was 23.9 ± 2.7 mm posteroproximal to a line perpendicular to the Blumensaat line that intersected the anterior margin of the medial femoral condyle cortex. Anteroposterior tibia images revealed that the ALB and PMB centers were located 0.2 ± 2.1 mm proximal and 4.9 ± 2.9 mm distal to the proximal joint line, respectively. The PCL attachment center was 1.6 ± 2.5 mm distal to the proximal joint line. On the lateral tibia view, the ALB center was 8.4 ± 1.8 mm, the PCL attachment center was 5.5 ± 1.7 mm, and the PMB center was 2.5 ± 1.5 mm superior to the champagne glass drop-off of the posterior tibia. CONCLUSION: Radiographic measurements from several clinically relevant views of the femur and tibia were reproducible with regard to the anatomic locations of the ALB and PMB centers. The measurements from the lateral femur and tibia views provided the most clinically pertinent radiographic measurements intraoperatively. CLINICAL RELEVANCE: This study established a set of clinically relevant radiographic guidelines for anatomic reconstruction of the PCL. The parameters set forth in this study can be used in both the intraoperative and postoperative settings for both single- and double-bundle PCL reconstructions.

Arthroscopically pertinent anatomy of the anterolateral and posteromedial bundles of the posterior cruciate ligament.

BACKGROUND: The clock-face method to identify the femoral posterior cruciate ligament (PCL) attachment has poor accuracy and reproducibility. Measurements of clinically relevant anatomic structures would provide more useful surgical guidance. The purpose of the present study was to describe the attachments of the anterolateral and posteromedial bundles of the PCL relative to relevant landmarks to assist with arthroscopic anatomic PCL reconstructions. METHODS: Dissections were performed on twenty nonpaired fresh-frozen cadaveric knees. RESULTS: The distal articular cartilage margin of the intercondylar notch had a consistent shape conforming to the attachments of the anterolateral and posteromedial bundles. The mean distance (and standard deviation) between the femoral centers of the anterolateral and posteromedial bundles was 12.1 ± 1.3 mm. The distal margins of the anterolateral and posteromedial bundles were a mean of 1.5 ± 0.8 mm and 5.8 ± 1.7 mm proximal to the notch articular cartilage, respectively. On the tibia, the lateral plateau articular cartilage, the medial meniscus attachment, and an osseous ridge ("bundle ridge") separating the anterolateral and posteromedial bundles were important arthroscopic landmarks. The mean distance between the tibial centers of the anterolateral and posteromedial bundles was 8.9 ± 1.2 mm. CONCLUSIONS: The pertinent landmarks identified during arthroscopic PCL reconstruction consistently marked the borders of the attachments of the anterolateral and posteromedial bundles. To guide femoral tunnel placement, the centers of both bundles should be triangulated relative to the reported landmarks. Furthermore, the distal edge of the femoral anterolateral bundle should be placed adjacent to the articular cartilage, whereas the posteromedial bundle should be centered, on average, 8.6 mm proximal to the cartilage margin, just distal to the medial intercondylar ridge. On the tibia, the PCL tunnel should be placed just anterosuperior to the bundle ridge, with use of the lateral articular cartilage and medial meniscus attachment to guide placement. CLINICAL RELEVANCE: The results of the present study can assist with more anatomic tunnel placement during single and double-bundle PCL reconstructions. The results also suggest that two reconstruction tunnels are needed to reconstruct the broad femoral attachment, whereas one reconstruction tunnel should be investigated further for the compact tibial attachment.

Arthroscopically pertinent landmarks for tunnel positioning in single-bundle and double-bundle anterior cruciate ligament reconstructions.

BACKGROUND: Quantification of the overall anterior cruciate ligament (ACL) and anteromedial (AM) and posterolateral (PL) bundle centers in respect to arthroscopically pertinent bony and soft tissue landmarks has not been thoroughly assessed. HYPOTHESIS: A standardized anatomical measurement method can quantitate the locations of the ACL and AM and PL bundle centers in reference to each other and anatomical landmarks. STUDY DESIGN: Descriptive laboratory study. METHODS: Quantification of the ACL and its bundle attachments was performed on 11 cadaveric knees using a radio frequency-tracking device. RESULTS: The tibial ACL attachment center was 7.5 mm medial to the anterior horn of the lateral meniscus, 13.0 mm anterior to the retro-eminence ridge, and 10.5 mm posterior to the ACL ridge. The femoral ACL attachment center was 1.7 mm proximal to the bifurcate ridge and 6.1 mm posterior to the lateral intercondylar ridge. The tibial AM attachment center was 8.3 mm medial to the anteromedial aspect of the lateral meniscus anterior horn, 17.8 mm anterior to the retro-eminence ridge, and 5.6 mm posterior to the ACL ridge. The femoral AM attachment center was 4.8 mm proximal to the bifurcate ridge and 7.1 mm posterior to the lateral intercondylar ridge. The tibial PL bundle attachment center was 6.6 mm medial to the posteromedial aspect of the lateral meniscus anterior horn, 10.8 mm anteromedial to the root attachment of the lateral meniscus posterior horn, and 8.4 mm anterior to the retro-eminence ridge. The femoral PL bundle attachment center was 5.2 mm distal to the bifurcate ridge and 3.6 mm posterior to the lateral intercondylar ridge. CONCLUSION: The authors developed a comprehensive compilation of measurements of arthroscopically pertinent bony and soft tissue landmarks that quantitate the ACL and its individual bundle attachment centers on the tibia and femur. CLINICAL RELEVANCE: These clinically relevant arthroscopic landmarks may enhance single- and double-bundle ACL reconstructions through improved tunnel placement.

Kinematic impact of anteromedial and posterolateral bundle graft fixation angles on double-bundle anterior cruciate ligament reconstructions.

BACKGROUND: Currently in double-bundle anterior cruciate ligament (ACL) reconstructions, the range of knee flexion angles that surgeons use for anteromedial (AM) and posterolateral (PL) bundle graft fixation spans from 0 degrees to 90 degrees for both bundle grafts. Despite the recent popularity of this procedure, no consensus exists on an optimal set of AM and PL graft fixation angles. HYPOTHESIS: Graft fixation angles that simulate the native tensioning relationship of the AM and PL bundles will produce kinematic results similar to the intact knee, while graft fixation angles that do not simulate this relationship will under- or overconstrain the knee. STUDY DESIGN: Controlled laboratory study. METHODS: Twelve cadaveric knees were biomechanically tested in the intact state, ACL-sectioned state, and a randomized order of 7 double-bundle ACL reconstructed states at multiple graft fixation angle combinations. For each test state, data were collected for 88 N anterior tibial loads, 10 N.m valgus torques, 5 N.m internal rotation torques, and 2 simulated pivot shift loads consisting of a 5 N.m internal rotation torque coupled with either a 10 N.m valgus torque or an 88 N anterior tibial load at 0 degrees, 20 degrees, 30 degrees, 60 degrees, and 90 degrees of knee flexion. RESULTS: The AM and PL graft fixation angle combinations of 0 degrees /0 degrees (AM graft fixation angle/PL graft fixation angle), 60 degrees /0 degrees, 45 degrees /15 degrees, and 75 degrees /15 degrees restored normal laxity to the reconstructed knee in all of the biomechanical tests. The 30 degrees /30 degrees, 60 degrees /60 degrees, and 90 degrees /90 degrees graft fixation angle combinations significantly restricted knee laxity compared with the intact state in various biomechanical tests. CONCLUSION: We found that as long as the PL bundle graft was fixed between 0 degrees and 15 degrees , the AM graft could be fixed up to 75 degrees without restricting knee laxity. However, fixation of the PL graft at 30 degrees of knee flexion and above significantly overconstrained the knee. CLINICAL RELEVANCE: This study provides a range of angles that can be used in double-bundle ACL reconstructions to restore normal knee stability without causing overconstraint.