Lee R. Leddy

Chondrosarcoma of bone.

Chondrosarcoma is a cartilage forming neoplasm, which is the second most common primary malignancy of bone. Clinicians who treat chondrosarcoma patients must determine the grade of the tumor, and must ascertain the likelihood of metastasis. Acral lesions are unlikely to metastasize, regardless of grade, whereas axial, or more proximal lesions are much more likely to metastasize than tumors found in the distal extremities with equivalent histology. Chondrosarcoma is resistant to both chemotherapy and radiation, making wide local excision the only treatment. Local recurrence is frequently seen after intralesional excision, thus wide local excision is sometimes employed despite significant morbidity, even in low-grade lesions. Chondrosarcoma is difficult to treat. The surgeon must balance the risk of significant morbidity with the ability to minimize the chance of local recurrence and maximize the likelihood of long-term survival.

The role of sentinel lymph node biopsy in select sarcoma patients: a meta-analysis.

BACKGROUND Sentinel lymph node (SLN) biopsy is a staging technique for occult lymph node disease. SLN biopsy has been applied to select patients with sarcoma, although the clinical utility remains uncertain. METHODS A PubMed/MEDLINE literature search was performed, and SLN biopsy outcomes were analyzed using a Bayesian meta-analytic approach to obtain point and interval estimates of rates of interest. RESULTS Sixteen studies involving SLN biopsy in patients with sarcoma were identified. Of 114 patients reported, 14 patients had positive SLNs (crude estimate, 12%; meta-analysis estimate, 17%). The meta-analysis false-negative rate was 29% (95% credible interval, 5%-59%). Recurrence and death rates in the SLN-positive group were higher than in the SLN-negative group. CONCLUSIONS This investigation highlights the current role of SLN biopsy in select patients with sarcoma for tumor staging. Questions regarding the high false-negative rate and management of micrometastatic lymphatic disease in patients with sarcoma still exist.

Rationale for reduced pressure reaming when stabilizing actual or impending pathological femoral fractures: a review of the literature

Surgical treatment for impending or actual pathologic femoral fractures due to metastatic carcinoma has been shown to improve pain and quality of life. Surgery usually involves manipulation of the intramedullary (IM) portion of the femur to provide adequate stability and to restore function. IM nailing is generally considered the preferred treatment over plate osteosynthesis for most areas of the femur due to load sharing capabilities. Several reports have shown a high incidence of oxygen desaturation, hypotension, fat or air embolism, and mortality in the surgical treatment of femoral metastatic disease. The patient with a metastatic lesion in the femur is at risk for cardiopulmonary complications associated with entering the IM canal. Complications and mortality reported in the literature are varied. Benefits of IM nailing of femoral lesions and associated complications in the literature are discussed. The theoretical benefit of aspiration and irrigation while reaming is also reviewed. Reaming while irrigating under negative pressure provided through suction may potentially minimize cardiopulmonary and oncologic complications.

The impact of race on the development of severe heterotopic ossification following acetabular fracture surgery

OBJECTIVES To determine the association between race on severe heterotopic ossification (HO) following acetabular fracture surgery. DESIGN Retrospective case control study. SETTING Level I university trauma centre. METHODS Two hundred and fifty-three patients who were surgically treated for acetabular fractures were retrospectively evaluated. Postoperative radiographs were evaluated for HO by a blinded musculoskeletal radiologist, and classified based on a modified Brooker classification. RESULTS Of the 253 patients that met inclusion and exclusion criteria, 175 (69%) were male and 78 (31%) were female. One hundred and fifty-four (61%) patients were Caucasian, and 99 (39%) were African American (AA). Fifty-five (21%) patients developed severe HO. Of those who developed severe HO, 25 were Caucasian (45%), 30 were African American (55%). Forty-one patients (75%) with severe HO were male, and 14 (25%) were female. No statistical differences (p>0.05) were found between groups in terms of age, days to surgery, GCS at presentation, surgical approach, perioperative HO prophylaxis, or AO/OTA fracture classification. The patient population was then stratified by race, gender, and race/gender. AA were more likely than Caucasians to develop severe HO (odds ratio [OR], 2.24; confidence interval [CI], 1.22-4.11). When gender was considered independent of race, no statistical differences (p>0.05) were observed (OR, 1.40; CI, 0.71-2.75). AA males were much more likely to develop severe HO when compared to Caucasian females (OR, 4.4; CI, 1.38-14.06). CONCLUSION Race is associated with different rates of severe HO formation following acetabular fracture surgery. AA patients are significantly more likely to develop severe HO following acetabular fracture surgery when compared to Caucasian patients.

How much tumor surgery do early-career orthopaedic oncologists perform?

BackgroundThere are few data on the types of procedures orthopaedic oncologists perform in their first years of practice. Because fellowships are graduating fellows each year and the number of tumor patients is limited, defining the practice patterns of early-career orthopaedic oncologists may help diminish early employment discontent and enhance workforce discussions.Questions/purposesThe aim of the study was to use the objective case log volumes of a cross-section of early career orthopaedic oncologists to describe (1) the number of operations performed annually; (2) the proportion of tumor, trauma, adult reconstruction, and other operations for individual participants, (3) individual practice characteristics that were associated with the number of tumor procedures; and (4) the sources of satisfaction and challenges in each individual’s career and surgical practice.MethodsFifteen fellowship-trained orthopaedic oncologists out of a potential pool of 33 (45%) in their first 4 years of practice responded to a survey by submitting complete operative case lists for a 2-year period. We recorded the type of procedure and determined associations between the annual number of tumor operations and total operative caseload, years in practice, and some details of individual practice patterns. Each participant completed a survey regarding practice-related sources of stress and satisfaction. A total of 5611 surgical cases were available for review. For the entire cohort, there were 3303 (59%) tumor procedures, 973 (17%) trauma, 890 (16%) adult reconstruction, and 445 (8%) other.ResultsThe median annual number of total operations was 214 (range, 63–356) and median annual number of tumor operations was 135 (range, 47–216). The median proportion of tumor operations in an individual practice was 56% (range, 43%–94%). The annual number of tumor operations correlated with the total annual number of operations (r = 0.73, p < 0.001). Sources of stress and satisfaction were similar to the general membership of the Musculoskeletal Tumor Society (MSTS), apart from more early-career surgeons regarding case volume as important (29 of 104 [28%] of MSTS versus 11 of 15 [73%] of early-career, p < 0.001).ConclusionsThe typical early-career orthopaedic tumor surgeon had fewer than 60% of his or her operative procedures directly related to the subject of his or her fellowship training in orthopaedic oncology. Overall, the challenges and rewards of clinical practice are similar to oncologic surgeons later in their career. This study is a first step in assessing early practice characteristics and may be of value to the prospective orthopaedic oncologist, fellowship educators, and the society in workforce discussions. Early-career practice patterns have not been previously presented, to our knowledge, for any subspecialty of orthopaedic surgery, and we hope that this study will stimulate similar efforts throughout the field.Level of EvidenceLevel IV, economic and decision analyses. See Guidelines for Authors for a complete description of levels of evidence.

Insufficiency Fracture Associated With Oncogenic Osteomalaciar

Oncogenic osteomalacia is a rare paraneoplastic syndrome of systemic bone demineralization secondary to a tumor-induced dysregulation of phosphorus metabolism. The tumors low prevalence, small size, and variable location often result in years of muscular weakness and bone pain before diagnosis. With complete treatment, patients symptoms swiftly dissipate. We report the case of a 63-year-old previously healthy man with a 20-month course of musculoskeletal symptoms before diagnosis and resection of a posterior tibial tumor. Postoperatively, the patient had returned to his previous lifestyle when an insufficiency fracture required prophylactic stabilization.

Abstract A46: The role of circulating fibroblast precursors in promoting metastatic sarcoma

Soft tissue sarcomas are malignant tumors that develop in connective tissue. Treatment with standard chemotherapeutic agents is often minimally effective and approximately half of all patients with soft tissue sarcoma experience disease recurrence and die of metastatic cancer. Therefore, the purpose of this study is to gain a better understanding of the soft tissue sarcoma metastatic environment in order to lead to the development of more effective therapies. Studies have shown that the tumor microenvironment plays a pivotal role in promoting tumor metastasis and one of the most prominent cell types of the tumor microenvironment is the carcinoma associated fibroblast (CAF). Our studies, based upon a murine single hematopoietic stem cell transplantation model have demonstrated that hematopoietic stem cells (HSCs) are a novel source for CAFs and their circulating fibroblast precursors (CFPs). Our research has also shown that murine CFPs are present in the peripheral blood, increase with tumor burden, and contribute to tumor growth. In vitro studies have shown that HSC-derived CFPs enhance tumor cell proliferation, migration, and invasion, processes critical to tumor metastasis in vivo. The role of human CFPs in metastasis of soft tissue sarcoma, however, has yet to be determined. It is our hypothesis that HSC derived CFPs promote sarcoma cell proliferation, migration, and invasion. In order to determine the role of CFPs in sarcoma metastasis, we established a method for culturing fibroblasts from peripheral blood obtained from patients diagnosed with metastatic sarcoma. These cultured cells were then characterized by immunohistochemistry to profile fibroblast and hematopoietic markers. In order to address the functional role of CFPs during sarcoma metastasis, we examined the ability of conditioned media from cultured CFPs from patients with metastatic sarcoma to influence the proliferation, migration, and invasion of HT-1080 cells, a human sarcoma line. Our immunohistochemical findings demonstrate that fibroblasts can be isolated from the circulation of patients with metastatic sarcoma and results from our functional assays indicate that cultured CFPs from patients with metastatic sarcoma promote the proliferation, migration, and invasion of HT-1080 cells. Given that proliferation, migration, and invasion of tumor cells are essential steps in the metastatic cascade, these findings suggest that CFPs promote tumor progression. Ongoing studies involve analysis of CFPs at various time points based upon chemotherapeutic treatment in order to evaluate differences in numbers of CFPs, marker expression, growth factor production, and ability to promote metastasis. Long term, these studies may identify novel biomarkers for disease progression as well as treatment efficacy, potentially leading to the development of more effective therapies for soft tissue sarcomas. Citation Format: Dayvia A. Laws, Andrew S. Kraft, Lee R. Leddy, Amanda C. LaRue. The role of circulating fibroblast precursors in promoting metastatic sarcoma. [abstract]. In: Abstracts: AACR Special Conference on Cellular Heterogeneity in the Tumor Microenvironment; 2014 Feb 26-Mar 1; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2015;75(1 Suppl):Abstract nr A46. doi:10.1158/1538-7445.CHTME14-A46

Total Hip Arthroplasty in a Patient with a Left Ventricular Assist Device

Left ventricular assist devices (LVADs) augment the cardiac function of patients with severe left-sided cardiac disease. These devices are typically used as a bridge to transplantation and have proven effective at improving longevity and overall quality of life1. Improved longevity results in increased numbers of noncardiac surgical procedures for other medical conditions2. Although these procedures carry obvious risk, they have been performed with favorable outcomes1-6. Infection is of utmost concern with noncardiac surgery in a patient with an LVAD. While infection rates have improved with the use of second-generation LVADs, the infection rate remains at 30% to 50%, with 20% to 27% classified as bloodstream infections7. The concerns regarding infection are especially important with arthroplasty procedures because implants are susceptible to biofilms, and complications from infection can be devastating. Also of concern is the nonpulsatile flow that the LVADs deliver, which can have serious implications when a patient is under general anesthesia and placed in the lateral position because preload and systemic vascular resistance are affected. Despite these risks, a literature search revealed two total knee arthroplasties that were performed in patients with LVADs4. Both patients developed postoperative infections related to the LVAD, but neither total knee arthroplasty became infected. In terms of cardiac function, total hip arthroplasty has been shown to be extremely effective at playing a role in improving cardiac function, with postarthroplasty patients showing substantial improvements in exercise duration, maximum workload, peak oxygen consumption, and percentage of predicted maximum oxygen uptake achieved by six months postsurgery8. We present a case of a total hip arthroplasty in a patient with a HeartMate II LVAD (Thoratec Corporation, Pleasanton, California). To the best of our knowledge, there are no previous reports in the literature of a …

Metachronous Aneurysmal Bone Cysts in a Fourteen-Year-Old Girl

Aneurysmal bone cysts (ABCs) were first described by Jaffe and Lichtenstein in 19421. Eighty percent of these lesions occur during the first two decades of life2; the most common location is the metaphysis of long bones. To the best of our knowledge, only four cases of individuals with multiple ABCs occurring over a period of time (metachronous ABCs) have been described to date3-6 (Table I). The cases all have been similar in presentation, imaging, and pathology to solitary ABCs; the only difference has been regarding the sex of the patient. While solitary ABCs have been shown to be predominant in females (62%)7, the reported cases of metachronous ABCs have all occurred in males. We report the case of an adolescent girl with multiple ABCs presenting separately in the proximal part of the femur and the distal part of the humerus over a five-month period. The patient and her parents were informed that data concerning the case would be submitted for publication, and they provided consent. View this table: TABLE I Reported Cases of Metachronous Aneurysmal Bone Cysts A healthy and active fourteen-year-old girl presented to the sports medicine clinic with unilateral hip pain. She had no history of trauma or an activity-related injury. Radiographs demonstrated a well-defined (5.4 × 2.8 cm) oval lucent geographic lesion in the proximal part of the femur, which initially was thought to be consistent with a unicameral bone cyst. At the short interval follow-up, the pain had worsened, and a new palpable mass was noted. Additional radiographs revealed substantial interval progression of the lesion with extension into the adjacent soft tissues with expansion of the bone (Fig. 1). Fig. 1 Anteroposterior radiograph demonstrates a lucent geographic lesion with a well-defined border (black arrow) in the right hip. However, there is focal extension …