Robert K. Heck

Cytoplasmic and/or nuclear accumulation of the β‐catenin protein is a frequent event in human osteosarcoma

The molecular events that precede the development of osteosarcoma, the most common primary malignancy of bone, are unclear, and concurrent molecular and genetic alterations associated with its pathogenesis have yet to be identified. Recent studies suggest that activation of β‐catenin signaling may play an important role in human tumorigenesis. To investigate the potential role of β‐catenin deregulation in human osteosarcoma, we analyzed a panel of 47 osteosarcoma samples for β‐catenin accumulation using immunohistochemistry. Potential activating mutations were investigated by sequencing exon 3 of the β‐catenin gene in genomic DNA isolated from tumor samples. Our findings revealed cytoplasmic and/or nuclear accumulation of β‐catenin in 33 of 47 samples (70.2%); however, mutation analysis failed to detect any genetic alterations within exon 3, suggesting that other regulatory mechanisms may play an important role in activating β‐catenin signaling in osteosarcoma. In our survival analysis, β‐catenin deregulation conferred a hazard ratio of 1.05, indicating that β‐catenin accumulation does not appear to be of prognostic value for osteosarcoma patients. When analyzed against other clinicopathologic parameters, β‐catenin accumulation correlated only with younger age at presentation (26.4 vs. 39.8 years). Nevertheless, our results demonstrate that the deregulation of β‐catenin signaling is a common occurrence in osteosarcoma that is implicated in the pathogenesis of osteosarcoma.

The incidence and prognosis of osteosarcoma skip metastases.

The poor prognosis for patients with osteosarcoma skip metastases has been established in the literature; however, most of the data in the literature concerning osteosarcoma skip metastases were collected before routine use of magnetic resonance imaging and before the use of modern multiagent chemotherapy regimens. This retrospective multiinstitutional study was done to evaluate the efficacy of magnetic resonance imaging to detect skip metastases and to evaluate the prognosis for these patients when treated with modern multiagent chemotherapy protocols. In a group of 155 patients who were younger than 26 years when diagnosed and treated for high-grade osteosarcoma of the long bones, 10 (6.5%) patients with skip metastases were identified. Eight of the 10 lesions were detected on pretreatment magnetic resonance imaging scans and two were detected only from the surgical pathology specimens. Five patients had concomitant pulmonary metastases at presentation and five patients had no other known site of diseases. All 10 patients died, with an average survival of 32.5 months (range 11–71 months). The five patients with only skip metastases at presentation survived an average of 27.2 months (range 15–44 months). Despite advances in the treatment of patients with osteosarcomas, those with skip metastases continue to have a poor prognosis, and they should be counseled regarding the limitations of current therapies.

Staging of Primary Malignancies of Bone

Staging of bone sarcomas is the process whereby patients are evaluated with regard to histology, as well as the local and distant extent, of disease. Bone sarcomas are staged based on grade, size, and the presence and location of metastases. The system is designed to help stratify patients according to known risk factors. Proper staging helps define the prognosis for patients and helps guide their treatment. Furthermore, staging allows meaningful comparisons to be done among groups of patients.

A Comparison Study of Staging Systems for Bone Sarcomas

A retrospective study of 250 patients treated at one institution was done to evaluate the prognostic significance of the new American Joint Committee on Cancer staging system compared with the Musculoskeletal Tumor Society staging system for patients with sarcomas of bone. Regarding the Musculoskeletal Tumor Society system, there were significant differences in survival among patients with Stage I, Stage II, and Stage III disease. There were no significant differences between patients with Stages I-A and I-B disease, nor between patients with Stages II-A and II-B disease. Similarly, regarding the new American Joint Committee on Cancer staging system, there were significant differences among patients with Stage I, Stage II, and Stage IV disease. No significant differences were seen between patients with Stages I-A and I-B disease, between patients with Stages II-A and II-B disease, nor between patients with Stages IV-A and IV-B disease. A significant advantage in the ability to predict prognosis for one staging system over the other staging system was not shown with the relatively small number of patients in this study.

Reconstruction of Noncontained Distal Femoral Defects with Polymethylmethacrylate and Crossed-Screw Augmentation: A Biomechanical Study

BACKGROUND Curettage and cementation with polymethylmethacrylate are frequently used in the treatment of aggressive benign bone lesions such as giant-cell tumors, but strength and stiffness of the reconstructed bone have been concerns. This biomechanical study was undertaken to determine whether augmenting the cement with crossed screws would result in a stronger reconstruction. METHODS Large noncontained defects were created in the medial femoral condyles of twenty matched pairs of human cadavera. Four groups were organized to compare three types of reconstruction: (1) polymethylmethacrylate alone, (2) polymethylmethacrylate and intramedullary Steinmann pins, and (3) polymethylmethacrylate with crossed screws engaging the opposite cortex. The specimens were subjected to 2000 compressive cycles and were subsequently monotonically loaded to failure under a controlled displacement rate. Failure load and stiffness were determined for each femur that survived the cycling process. RESULTS Femora reconstructed with crossed screws and cement failed at higher loads and had greater stiffness than those reconstructed with cement alone (p = 0.025 and p = 0.0007) or cement augmented with intramedullary Steinmann pins (p = 0.019). Failure of femora reconstructed with cement and crossed screws occurred through an extra-articular transverse fracture, while failure in those with cement alone and cement with Steinmann pins occurred through an intra-articular (intercondylar) fracture. CONCLUSIONS In this in vitro cadaver study, augmentation of polymethylmethacrylate cement with crossed screws resulted in a stronger reconstruction of distal femoral tumor defects than that obtained with cement alone or with cement and intramedullary Steinmann pins.

Use of a smooth press-fit stem preserves physeal growth after tumor resection

We conducted this study to determine whether the small-diameter, press-fit stem of a novel, noninvasive expandable endoprosthetic device implanted in the limbs of 6 pediatric patients with Stage IIB osteosarcoma affected the growth of the physis through which the stem was inserted. Local control of the tumor necessitated resection of the involved growth plate, and implantation of the device required penetration of the adjacent uninvolved bone, through the growth plate, by the stem of the device. We measured longitudinal growth and the rate of growth of the adjacent uninvolved bone in the salvaged limb and of the equivalent bone in the unoperated contralateral limb. In all cases but one (in which the patient’s growth in the contralateral limb appeared complete), longitudinal growth continued in the limb into which the device was implanted: the adjacent uninvolved bone in the salvaged limb grew by an average of 2.4 cm, and the equivalent bone in the unoperated contralateral limb grew by an average of 2.3 cm. We conclude that implantation of a smooth, press-fit stem through the central portion of the uninvolved adjacent physis does not result in growth retardation or arrest.

Histoplasma Osteomyelitis Simulating Giant-Cell Tumor of the Distal Part of the Radius: A Case Report

Histoplasmosis is a ubiquitous fungal infection endemic to many regions in North America. Mild pulmonary infection with Histoplasma capsulatum is common, but musculoskeletal involvement is rare. We report a case of isolated Histoplasma osteomyelitis presenting as giant-cell tumor of the distal part of the radius. We found no other reported case of histoplasmosis masquerading as giant-cell tumor or of isolated Histoplasma osteomyelitis in a young, healthy patient. The patient was informed that data concerning the case would be submitted for publication, and he consented; our institutional review board exempts case reports from the approval process. A thirty-three-year-old, right-hand-dominant, otherwise healthy man presented to the orthopaedic clinic with an approximately three-month history of pain in the left wrist. The patient denied any history of recent trauma to the extremity and reported no respiratory or systemic illness preceding the wrist pain. The medical history was notable only for an uneventful recovery following a gunshot wound to the left second metacarpal years earlier. He reported no fever, chills, or other constitutional symptoms and had recently screened negative for the human immunodeficiency virus (HIV). He had moved back to Memphis, Tennessee, six years before presentation after having lived in Dallas, Texas, for several years. Physical examination revealed that the patient was afebrile and that the vital signs were within normal limits. Examination of the left wrist revealed tenderness to palpation over the distal part of the radius but no palpable masses or overlying skin changes. The patient had full range of motion of the wrist. He was neurologically intact and had a palpable radial pulse. The white blood-cell count was 3600 μL (3.6 × 109/L), and the hematocrit was 39%. Radiographs of the wrist demonstrated a radiolucent lesion in the lateral aspect of the distal radial epiphysis, with sharp borders and mild …

Errors in the MRI evaluation of musculoskeletal tumors and tumorlike lesions

Interpretation of an MRI of a suspected musculoskeletal neoplasm can be extremely difficult. Fifty-six MRIs originally evaluated by outside radiologists were independently evaluated by an expert panel consisting of three specialized musculoskeletal radiologists. The outside reports were then graded based upon accuracy and completeness of the differential diagnosis. We compared the expert opinions with those of the outside radiologists. According to the expert panel, only 30 of the 56 (54%) outside reports listed the most likely diagnosis as such and only 35 (63%) listed it at all. A complete appropriate differential diagnosis was listed in only 22 (39%) of the outside reports. Furthermore, 18 (32%) of the outside reports listed diagnoses judged to be extremely unlikely by the experts. In a subset of 15 patients with images that the expert panel had judged diagnostic of specific entities, only nine of the outside reports listed the correct diagnosis as such and only 10 listed it at all. Furthermore, 11 (73%) of the outside reports listed extremely unlikely possibilities for these diagnostic images. We found a substantial difference between the expert and the outside opinions.Level of Evidence: Level III, diagnostic study. See Guidelines for Authors for a complete description of levels of evidence.

Reconstruction of noncontained proximal tibial defects with divergent screws and cement.

Postoperative fracture is a well described complication following curettage and cementation of aggressive benign bone tumors. We asked whether: (1) the addition of diverging screws that engage the opposite cortex increase the strength and rigidity of the construct in the proximal tibia compared with (a) cement alone and (b) would cement with intramedullary Steinmann pins; and (2) the modes of failure be different for those constructs. The average load to failure for tibias reconstructed with cement augmented with diverging screws (6321 ± 681 N) was higher than for tibias reconstructed with cement alone (2343 ± 222 N). The average load to failure for tibias reconstructed with cement augmented with diverging screws (6885 ± 445 N) was higher than for tibias reconstructed with cement and intramedullary Steinmann pins (5218 ± 941 N). Furthermore, constructs with cement augmented with diverging screws were less likely to fail by an intraarticular fracture than other types of constructs. Our data support the use of diverging screws that engage the opposite cortex to augment the strength of the construct when using acrylic cement to fill noncontained defects after curettage of the proximal tibia. This more stable, stronger construct might allow earlier mobilization and rehabilitation after curettage, with a decreased risk of fracture.

Distal femoral replacement for acute distal femoral fractures in elderly patients

Objectives: To evaluate outcomes and complications using cemented modular distal femoral replacement in elderly patients with distal femoral fractures. Design: Retrospective chart review, case series. Setting: A Level 1 and Level 2 trauma center, both tertiary referral hospitals. Patients/Participants: Eighteen patients older than 60 years (average age 77 years) who had cemented distal femoral replacement for distal femoral fractures (comminuted, intraarticular, osteoporotic, arthritic) between 2005 and 2013. Patients with previous knee surgery were excluded. Intervention: Cemented modular distal femoral replacement. Main Outcome Measures: Implant status, complications, Knee Society Score, Musculoskeletal Tumor Society score, and Western Ontario and McMaster Osteoarthritis Index. Results: All patients were extremely or very satisfied with their outcomes. For patients with functional outcome data, Knee Society Score averaged 85.7 with a functional score of 35, Musculoskeletal Tumor Society score averaged 19.2, and Western Ontario and McMaster Osteoarthritis Index score averaged 23.1 at an average follow-up of 2.3 years. Range of motion was 1–99 degrees. Implant-related complications occurred in 2 patients (11%); one required revision to total femoral replacement because of periprosthetic fracture and the other had a deep infection that required exchange of the components. No patient had aseptic loosening or patellar maltracking. There were no perioperative deaths or late amputations. Conclusions: Cemented modular distal femoral replacement is a viable treatment option in elderly patients that permits immediate full weight-bearing, with most patients returning to preoperative functional status. Level of Evidence: Therapeutic Level IV. See Instructions for Authors for a complete description of levels of evidence.