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1.
Clin Cancer Res ; 30(4): 849-864, 2024 02 16.
Article in English | MEDLINE | ID: mdl-37703185

ABSTRACT

PURPOSE: Models to study metastatic disease in rare cancers are needed to advance preclinical therapeutics and to gain insight into disease biology. Osteosarcoma is a rare cancer with a complex genomic landscape in which outcomes for patients with metastatic disease are poor. As osteosarcoma genomes are highly heterogeneous, multiple models are needed to fully elucidate key aspects of disease biology and to recapitulate clinically relevant phenotypes. EXPERIMENTAL DESIGN: Matched patient samples, patient-derived xenografts (PDX), and PDX-derived cell lines were comprehensively evaluated using whole-genome sequencing and RNA sequencing. The in vivo metastatic phenotype of the PDX-derived cell lines was characterized in both an intravenous and an orthotopic murine model. As a proof-of-concept study, we tested the preclinical effectiveness of a cyclin-dependent kinase inhibitor on the growth of metastatic tumors in an orthotopic amputation model. RESULTS: PDXs and PDX-derived cell lines largely maintained the expression profiles of the patient from which they were derived despite the emergence of whole-genome duplication in a subset of cell lines. The cell lines were heterogeneous in their metastatic capacity, and heterogeneous tissue tropism was observed in both intravenous and orthotopic models. Single-agent dinaciclib was effective at dramatically reducing the metastatic burden. CONCLUSIONS: The variation in metastasis predilection sites between osteosarcoma PDX-derived cell lines demonstrates their ability to recapitulate the spectrum of the disease observed in patients. We describe here a panel of new osteosarcoma PDX-derived cell lines that we believe will be of wide use to the osteosarcoma research community.


Subject(s)
Bone Neoplasms , Cyclic N-Oxides , Indolizines , Osteosarcoma , Pyridinium Compounds , Humans , Animals , Mice , Disease Models, Animal , Drug Evaluation, Preclinical , Xenograft Model Antitumor Assays , Osteosarcoma/drug therapy , Osteosarcoma/genetics , Osteosarcoma/metabolism , Cell Line, Tumor , Bone Neoplasms/drug therapy , Bone Neoplasms/genetics , Bone Neoplasms/metabolism
2.
Skeletal Radiol ; 2023 Dec 01.
Article in English | MEDLINE | ID: mdl-38036751

ABSTRACT

Botryomycosis is a rare granulomatous response to chronic bacterial infection most frequently associated with Staphylococcus aureus. This disease, which predominantly affects immunocompromised patients, may present with cutaneous, visceral, or soft tissue manifestations. Soft tissue involvement typically has an aggressive mass-like appearance on imaging which can be concerning for malignancy. In immunocompromised patients, botryomycosis can resemble fungal infection both clinically and histologically; therefore, definitive diagnosis requires tissue sampling along with histological and microbiological analysis. Presented here is a 25-year-old man with an enlarging intramuscular soft tissue mass of the right forearm as his first presentation of undiagnosed acquired immunodeficiency syndrome (AIDS). MR imaging showed a mildly T2 hyperintense and enhancing mass with infiltrative margins extending through tissue planes. Biopsy of the mass revealed Staphylococcus aureus-associated botryomycosis, which improved with nonsurgical treatment employing antibiotics. Unfortunately, the patient subsequently expired from other manifestations of his new AIDS diagnosis. This case describes the MR and PET-CT appearance of botryomycosis and also underscores that infection can mimic sarcoma, particularly in the setting of immunodeficiency.

3.
J Bone Joint Surg Am ; 105(Suppl 1): 49-56, 2023 07 19.
Article in English | MEDLINE | ID: mdl-37466580

ABSTRACT

BACKGROUND: Although there is evidence suggesting that postoperative infection confers a survival benefit in osteosarcoma treated with resection and endoprosthetic reconstruction, there have been no prospective studies to date to support these findings. This secondary analysis of Prophylactic Antibiotic Regimens in Tumor Surgery (PARITY) study data examines the relationship between surgical site infection (SSI) and disease progression within 12 months after limb salvage surgery. METHODS: The PARITY trial was an international, multicenter, prospective randomized controlled trial of 604 patients who underwent resection of a lower-extremity bone tumor and endoprosthetic reconstruction. Our primary outcome was progression-free survival (PFS) at 1 year following surgery among the patients with osteosarcoma. Subgroup analyses by disease stage at presentation and infection severity were also performed. Cox proportional hazard models were employed to examine the association between clinical and tumor characteristics, SSI, and PFS. Kaplan-Meier analysis was used to determine the effect of SSI on PFS. RESULTS: The 274 PARITY patients with osteosarcoma were included in this secondary analysis. Thirty-two (11.7%) of the patients presented with metastasis at baseline; 53 (19.3%) of the patients developed an SSI. There was no difference in 1-year PFS between patients with and without SSI. There was no decreased risk of disease progression at 1 year in patients with localized disease at baseline who developed an SSI (hazard ratio [HR] = 1.21; 95% confidence interval [CI] = 0.64 to 2.28). Infection was associated with increased disease progression at 1 year in patients with baseline metastases (HR = 4.26; 95% CI = 1.11 to 16.3). CONCLUSIONS: No positive association was detected between postoperative infection and PFS at 1 year following surgery in this secondary analysis of prospective data. However, this analysis suggests infection could be a risk factor for early disease progression in patients with baseline metastases, and future investigations may better elucidate the association between disease burden and the host immune response to advance immunotherapeutic strategies for osteosarcoma. LEVEL OF EVIDENCE: Prognostic Level II. See Instructions for Authors for a complete description of levels of evidence.


Subject(s)
Bone Neoplasms , Osteosarcoma , Humans , Disease Progression , Limb Salvage , Lower Extremity/surgery , Progression-Free Survival , Retrospective Studies , Surgical Wound Infection/etiology , Surgical Wound Infection/surgery
4.
bioRxiv ; 2023 Jan 20.
Article in English | MEDLINE | ID: mdl-36711882

ABSTRACT

Models to study metastatic disease in rare cancers are needed to advance preclinical therapeutics and to gain insight into disease biology, especially for highly aggressive cancers with a propensity for metastatic spread. Osteosarcoma is a rare cancer with a complex genomic landscape in which outcomes for patients with metastatic disease are poor. As osteosarcoma genomes are highly heterogeneous, a large panel of models is needed to fully elucidate key aspects of disease biology and to recapitulate clinically-relevant phenotypes. We describe the development and characterization of osteosarcoma patient-derived xenografts (PDXs) and a panel of PDX-derived cell lines. Matched patient samples, PDXs, and PDX-derived cell lines were comprehensively evaluated using whole genome sequencing and RNA sequencing. PDXs and PDX-derived cell lines largely maintained the expression profiles of the patient from which they were derived despite the emergence of whole-genome duplication (WGD) in a subset of cell lines. These cell line models were heterogeneous in their metastatic capacity and their tissue tropism as observed in both intravenous and orthotopic models. As proof-of-concept study, we used one of these models to test the preclinical effectiveness of a CDK inhibitor on the growth of metastatic tumors in an orthotopic amputation model. Single-agent dinaciclib was effective at dramatically reducing the metastatic burden in this model.

5.
J Surg Oncol ; 127(1): 148-158, 2023 Jan.
Article in English | MEDLINE | ID: mdl-36112398

ABSTRACT

BACKGROUND: Expandable endoprostheses can be used to equalize limb length for pediatric patients requiring reconstruction following large bony oncologic resections. Outcomes of the Compress® Compliant Pre-Stress (CPS) spindle paired with an Orthopedic Salvage System expandable distal femur endoprosthesis have not been reported. METHODS: We conducted a multi-institutional retrospective study of pediatric patients with distal femoral bone sarcomas reconstructed with the above endoprostheses. Statistical analysis utilized Kaplan-Meier survival technique and competing risk analysis. RESULTS: Thirty-six patients were included from five institutions. Spindle survivorship was 86.3% (95% confidence interval [CI], 67.7-93.5) at 10 years. Two patients had a failure of osseointegration (5.7%), both within 12 months. Twenty-two (59%) patients had 70 lengthening procedures, with mean expansions of 3.2 cm (range: 1-9) over 3.4 surgeries. The expandable mechanism failed in eight patients with a cumulative incidence of 16.1% (95% CI, 5.6-31.5) at 5 years. Twenty-nine patients sustained International Society of Limb Salvage failures requiring 63 unplanned surgeries. Periprosthetic joint infection occurred in six patients (16.7%). Limb preservation rate was 91% at 10 years. CONCLUSIONS: There is a high rate of osseointegration of the Compress® spindle among pediatric patients when coupled with an expandable implant. However, there is a high rate of expansion mechanism failure and prosthetic joint infections requiring revision surgery. LEVEL OF EVIDENCE: Level IV, therapeutic study.


Subject(s)
Bone Neoplasms , Femoral Neoplasms , Child , Humans , Femoral Neoplasms/surgery , Prosthesis Design , Retrospective Studies , Prosthesis Implantation/methods , Prosthesis Failure , Osteotomy , Treatment Outcome , Risk Factors , Femur/surgery , Reoperation , Bone Neoplasms/surgery
6.
J Natl Compr Canc Netw ; 20(11): 1204-1214, 2022 11.
Article in English | MEDLINE | ID: mdl-36351335

ABSTRACT

Gastrointestinal stromal tumors (GIST) are the most common type of soft tissue sarcoma that occur throughout the gastrointestinal tract. Most of these tumors are caused by oncogenic activating mutations in the KIT or PDGFRA genes. The NCCN Guidelines for GIST provide recommendations for the diagnosis, evaluation, treatment, and follow-up of patients with these tumors. These NCCN Guidelines Insights summarize the panel discussion behind recent important updates to the guidelines, including revised systemic therapy options for unresectable, progressive, or metastatic GIST based on mutational status, and updated recommendations for the management of GIST that develop resistance to specific tyrosine kinase inhibitors.


Subject(s)
Gastrointestinal Stromal Tumors , Humans , Gastrointestinal Stromal Tumors/diagnosis , Gastrointestinal Stromal Tumors/genetics , Gastrointestinal Stromal Tumors/therapy , Receptor, Platelet-Derived Growth Factor alpha/genetics , Proto-Oncogene Proteins c-kit/genetics , Mutation
7.
J Natl Compr Canc Netw ; 20(7): 815-833, 2022 07.
Article in English | MEDLINE | ID: mdl-35830886

ABSTRACT

Soft tissue sarcomas (STS) are rare malignancies of mesenchymal cell origin that display a heterogenous mix of clinical and pathologic characteristics. STS can develop from fat, muscle, nerves, blood vessels, and other connective tissues. The evaluation and treatment of patients with STS requires a multidisciplinary team with demonstrated expertise in the management of these tumors. The complete NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Soft Tissue Sarcoma provide recommendations for the diagnosis, evaluation, and treatment of extremity/superficial trunk/head and neck STS, as well as retroperitoneal/intra-abdominal STS, desmoid tumors, and rhabdomyosarcoma. This portion of the NCCN Guidelines discusses general principles for the diagnosis and treatment of retroperitoneal/intra-abdominal STS, outlines treatment recommendations, and reviews the evidence to support the guidelines recommendations.


Subject(s)
Sarcoma , Soft Tissue Neoplasms , Extremities/pathology , Humans , Medical Oncology , Sarcoma/drug therapy , Sarcoma/therapy , Soft Tissue Neoplasms/diagnosis , Soft Tissue Neoplasms/pathology , Soft Tissue Neoplasms/therapy
8.
Pediatr Emerg Med Pract ; 18(7): 1-20, 2021 Jul.
Article in English | MEDLINE | ID: mdl-34196516

ABSTRACT

Musculoskeletal pain is a common chief complaint of children in the emergency department. Although nonspecific and typically benign, musculoskeletal pain should be investigated thoroughly with consideration for an underlying bone tumor, especially when it is a recurrent visit for pain. This issue reviews the specific signs, symptoms, and unique presentations the emergency clinician should know when evaluating a pediatric patient with musculoskeletal pain. Additionally, assessment of relevant radiographic findings to assist in differentiating bone tumors and guide further management are discussed.


Subject(s)
Bone Neoplasms/diagnosis , Bone Neoplasms/therapy , Emergency Service, Hospital , Adolescent , Chest Pain/diagnosis , Child , Child, Preschool , Female , Histiocytosis, Langerhans-Cell/diagnosis , Histiocytosis, Langerhans-Cell/therapy , Humans , Infant , Male , Musculoskeletal Pain/diagnosis , Osteosarcoma/diagnosis , Osteosarcoma/therapy , Pediatric Emergency Medicine/methods , Practice Guidelines as Topic , Radiography/methods , Sarcoma, Ewing/diagnosis , Sarcoma, Ewing/therapy
9.
Cancer Immunol Immunother ; 70(10): 3031-3040, 2021 Oct.
Article in English | MEDLINE | ID: mdl-33864502

ABSTRACT

BACKGROUND: Soft-tissue sarcomas (STS) are a rare group of mesenchymal malignancies that account for approximately 1% of adult human cancer. Undifferentiated pleomorphic sarcoma (UPS) is one of the most common subtypes of adult STS. Clinical stratification of UPS patients has not evolved for decades and continues to rely on tumor-centric metrics including tumor size and depth. Our understanding of how the tumor microenvironment correlates to these clinicopathologic parameters remains limited. METHODS: Here, we performed single-cell flow cytometric immune-based profiling of 15 freshly resected UPS tumors and integrated this analysis with clinical, histopathologic, and outcomes data using both a prospective and retrospective cohort of UPS patients. RESULTS: We uncovered a correlation between physiologic and anatomic properties of UPS tumors and the composition of immune cells in the tumor microenvironment. Specifically, we identified an inverse correlation between tumor-infiltrating CD8 + T cells and UPS tumor size; and a positive correlation between tumor-infiltrating CD8 + T cells and overall survival. Moreover, we demonstrate an association between anatomical location (deep or superficial) and frequency of CD4 + PD1hi infiltrating T cells in UPS tumors. CONCLUSIONS: Our study provides an immune-based analysis of the tumor microenvironment in UPS patients and describes the different composition of tumor infiltrating lymphocytes based on size and tumor depth.


Subject(s)
Sarcoma/physiopathology , Soft Tissue Neoplasms/physiopathology , Aged , Aged, 80 and over , Cohort Studies , Female , Humans , Male , Middle Aged , Prospective Studies , Retrospective Studies , Tumor Microenvironment
10.
Skeletal Radiol ; 50(4): 821-825, 2021 Apr.
Article in English | MEDLINE | ID: mdl-32944815

ABSTRACT

Fibroma-like perivascular epithelioid cell (PEComa) tumor is an extremely rare family of mesenchymal tumors composed of cells co-expressing melanocytic and myogenic markers. To date, 13 cases of primary bone PEComa have been reported in the literature and five reported fibroma-like PEComas were found in the soft tissues of patients with tuberous sclerosis (TSC). However, no fibroma-like PEComa has been reported in bone, either sporadic or TSC-associated. Here we report the case of a 22-year-old man with known TSC, who presented for evaluation of an asymptomatic mass in his left fibula diaphysis that had been present for 5 years. He had no activity-related pain, numbness, weakness, or limitations in range of motion. Both 3-T MRI and CT demonstrated a tumor originating from the midshaft middiaphyseal fibula. Axial T1-weighted and fat-saturated T2-weighted fast spin echo images showed a well-defined lesion in the fibula with extension into the surrounding soft tissues. Whole body bone scan was negative for metastasis using technetium-99m. Renal ultrasound was unremarkable with no evidence of angiomyolipoma. Histopathology demonstrated isolated spindle cells in a dense collagenous matrix. By immunohistochemical staining, tumor cells were positive for HMB-45 and MiTF and partially positive for alpha-smooth muscle actin supporting a diagnosis of fibroma-like PEComa of the midshaft fibula. Although fibroma-like PEComa of bone is very rare, a bone tumor in the setting of TSC should raise suspicion for the diagnosis, in particular if histology demonstrates rare epithelioid cells in a densely fibrotic stroma.


Subject(s)
Bone Neoplasms , Fibroma , Kidney Neoplasms , Perivascular Epithelioid Cell Neoplasms , Tuberous Sclerosis , Biomarkers, Tumor , Bone Neoplasms/diagnostic imaging , Fibroma/diagnostic imaging , Fibroma/surgery , Humans , Male , Perivascular Epithelioid Cell Neoplasms/diagnostic imaging , Perivascular Epithelioid Cell Neoplasms/surgery , Young Adult
11.
J Natl Compr Canc Netw ; 18(12): 1604-1612, 2020 12 02.
Article in English | MEDLINE | ID: mdl-33285515

ABSTRACT

The NCCN Guidelines for Soft Tissue Sarcoma provide recommendations for the diagnosis, evaluation, treatment, and follow-up for patients with soft tissue sarcomas. These NCCN Guidelines Insights summarize the panel discussion behind recent important updates to the guidelines, including the development of a separate and distinct guideline for gastrointestinal stromal tumors (GISTs); reconception of the management of desmoid tumors; inclusion of further recommendations for the diagnosis and management of extremity/body wall, head/neck sarcomas, and retroperitoneal sarcomas; modification and addition of systemic therapy regimens for sarcoma subtypes; and revision of the principles of radiation therapy for soft tissue sarcomas.


Subject(s)
Sarcoma , Soft Tissue Neoplasms , Extremities , Gastrointestinal Stromal Tumors , Humans , Practice Guidelines as Topic , Retroperitoneal Neoplasms , Sarcoma/diagnosis , Sarcoma/therapy , Soft Tissue Neoplasms/diagnosis , Soft Tissue Neoplasms/therapy
12.
J Bone Jt Infect ; 4(1): 40-49, 2019.
Article in English | MEDLINE | ID: mdl-30755847

ABSTRACT

Cutibacterium (formerly Propionibacterium) acnes13, 16 is a slow growing, gram-positive bacteria that is naturally found in higher concentrations as skin flora on the chest and back, as well as in other areas with greater numbers of hair follicles.25, 37 Most of the reported cases of C. acnes shoulder girdle infection follow arthroplasty surgery,18, 20, 26, 27, 32, 35 which then often requires debridement, administration of intravenous antibiotics, and surgical revision of the implanted device.12, 15, 21, 28-30 In a recent study, 56% of 193 shoulder revisions had a positive culture, 70% of which grew C. acnes.30 Despite the relatively common presumed association of C. acnes humeral osteomyelitis with prosthetic infection, infection of the scapula or clavicle secondary to C. acnes is rare.4, 23, 36 Osteomyelitis of the clavicle involving any organism is also an uncommon event that can arise spontaneously via presumed hematogenous spread, or secondary to open fractures or internal fixation.6, 33 The most commonly found organism in clavicular osteomyelitis is Staphylococcus aureus.9 We here report two cases of clavicular infection secondary to C. acnes that were not associated with implants.

13.
Orthop J Sports Med ; 6(7): 2325967118785854, 2018 Jul.
Article in English | MEDLINE | ID: mdl-30046634

ABSTRACT

BACKGROUND: The underlying cause of glenohumeral arthritis is poorly understood. Glenohumeral arthrosis patterns have been classified and described, and differential contact stresses within the joint have been implicated as a cause of joint degeneration, but the intrinsic cause of degeneration patterns in the glenohumeral joint (GHJ) remains largely unknown. PURPOSE/HYPOTHESIS: The purpose of this study was to assess morphological and mechanical differences in articular cartilage (AC) and subchondral bone (SCB) of the glenoid and humeral head in matched cadaveric specimens. We hypothesized that there would be significant zone-dependent differences between the intrinsic characteristics (AC thickness, SCB thickness, compressive forces) of the glenoid and humeral head. STUDY DESIGN: Descriptive laboratory study. METHODS: Ten human cadaveric GHJs (mean age, 60.2 years) were dissected to expose articular surfaces to facilitate biomechanical testing. A 2-mm and 6-mm osteochondral plug was harvested at 5 zones (central, anterior, posterior, inferior, superior) on the glenoid and humeral head (N = 200 plugs). Each 2-mm core was histologically sectioned and stained with hematoxylin and eosin. AC thickness measurements were taken using light microscopy. The 6-mm plugs were imaged using micro-computed tomography to measure SCB thickness. After imaging, AC specimens were removed from the SCB and tested in confined compression. The compressive aggregate modulus (HA0), compressive stiffening coefficient (ß), and compressive modulus at 16% strain (HA0.16) and at 50% strain (HA0.50) were calculated. RESULTS: The overall AC thickness was significantly greater on the glenoid. The glenoid also had significantly thicker AC at the inferior, posterior, and superior zones as well as significantly higher SCB thickness overall and significantly greater SCB thickness at the anterior and central zones. The glenoid had significantly greater overall HA0.50 and HA0.50 values at the superior zone and had a significantly greater overall compressive stiffening coefficient (ß). CONCLUSION: The glenoid had thicker AC, thicker SCB, and greater compressive stiffness at high strain. CLINICAL RELEVANCE: These intrinsic differences may help better elucidate the cause of differential degeneration patterns between the glenoid and humeral head.

14.
Indian J Orthop ; 52(1): 77-80, 2018.
Article in English | MEDLINE | ID: mdl-29416174

ABSTRACT

Sarcomas are primary malignancies of the connective tissues. They are exceedingly rare in adults, but much more common in children. The historically recent advent of cytotoxic chemotherapy for pediatric sarcomas has revolutionized the treatment of these diseases and dramatically improved their prognoses. There is thus a population of pediatric sarcoma survivors that are "coming of age" as adults. However, this progress is not without consequences. Due to aggressive treatment protocols that include various combinations of surgery, chemotherapy, and radiation therapy, pediatric sarcoma survivors are at risk of myriad physical, medical, and psychological difficulties as they enter adulthood. These include but are not limited to physical disabilities, chemotherapy-induced cardiac issues, second malignancies, and anxiety. These patients pose unique challenges to their adult primary care physicians. One possible solution to these challenges is multidisciplinary sarcoma survivorship clinics. By paying greater attention to the unique issues of pediatric sarcoma survivors, involved physicians can maximize the physical and emotional health of pediatric sarcoma survivors.

15.
Mol Cancer Ther ; 16(12): 2701-2710, 2017 Dec.
Article in English | MEDLINE | ID: mdl-28830983

ABSTRACT

Polymeric nanocarriers such as N-(2-hydroxypropyl) methacrylamide (HPMA) copolymers deliver drugs to solid tumors and avoid the systemic toxicity of conventional chemotherapy. Because HPMA copolymers can target sites of inflammation and accumulate within innate immune cells, we hypothesized that HPMA copolymers could target tumor-associated macrophages (TAM) in both primary and metastatic tumor microenvironments. We verified this hypothesis, first in preliminary experiments with isolated bone marrow macrophage cultures in vitro and subsequently in a spontaneously metastatic murine breast cancer model generated from a well-established, cytogenetically characterized 4T1 breast cancer cell line. Using our standardized experimental conditions, we detected primary orthotopic tumor growth at 7 days and metastatic tumors at 28 days after orthotopic transplantation of 4T1 cells into the mammary fat pad. We investigated the uptake of HPMA copolymer conjugated with Alexa Fluor 647 and folic acid (P-Alexa647-FA) and HPMA copolymer conjugated with IRDye 800CW (P-IRDye), following their retroorbital injection into the primary and metastatic tumor-bearing mice. A significant uptake of P-IRDye was observed at all primary and metastatic tumor sites in these mice, and the P-Alexa647-FA signal was found specifically within CD11b+ TAMs costained with pan-macrophage marker CD68. These findings demonstrate, for the first time, a novel capacity of a P-Alexa647-FA conjugate to colocalize to CD11b+CD68+ TAMs in both primary and metastatic breast tumors. This underscores the potential of this HPMA nanocarrier to deliver functional therapeutics that specifically target tumor-promoting macrophage activation and/or polarization during tumor development. Mol Cancer Ther; 16(12); 2701-10. ©2017 AACR.


Subject(s)
Breast Neoplasms/genetics , Macrophages/metabolism , Methacrylates/metabolism , Animals , Breast Neoplasms/metabolism , Disease Models, Animal , Female , Humans , Mice , Neoplasm Metastasis , Polymers
16.
Cancer Metastasis Rev ; 35(2): 333-46, 2016 Jun.
Article in English | MEDLINE | ID: mdl-27067726

ABSTRACT

The skeleton is frequently a secondary growth site of disseminated cancers, often leading to painful and devastating clinical outcomes. Metastatic cancer distorts bone marrow homeostasis through tumor-derived factors, which shapes different bone tumor microenvironments depending on the tumor cells' origin. Here, we propose a novel insight on tumor-secreted Galectin-3 (Gal-3) that controls the induction of an inflammatory cascade, differentiation of osteoblasts, osteoclasts, and bone marrow cells, resulting in bone destruction and therapeutic failure. In the approaching era of personalized medicine, the current treatment modalities targeting bone metastatic environments are provided to the patient with limited consideration of the cancer cells' origin. Our new outlook suggests delivering individual tumor microenvironment treatments based on the expression level/activity/functionality of tumor-derived factors, rather than utilizing a commonly shared therapeutic umbrella. The notion of "Gal-3-associated bone remodeling" could be the first step toward a specific personalized therapy for each cancer type generating a different bone niche in patients afflicted with non-curable bone metastasis.


Subject(s)
Bone Neoplasms/metabolism , Bone Neoplasms/pathology , Galectin 3/metabolism , Tumor Microenvironment , Bone Neoplasms/genetics , Bone Neoplasms/secondary , Bone Remodeling , Carrier Proteins/metabolism , Cell Communication , Cell Differentiation , Cell Transformation, Neoplastic/genetics , Cell Transformation, Neoplastic/metabolism , Cytokines/metabolism , Female , Galectin 3/genetics , Humans , Male , Myeloid Cells/cytology , Myeloid Cells/metabolism , Osteoblasts/metabolism , Osteoclasts/metabolism , Protein Binding , Signal Transduction , Tumor Microenvironment/genetics
17.
Clin Orthop Relat Res ; 474(2): 528-36, 2016 Feb.
Article in English | MEDLINE | ID: mdl-26394638

ABSTRACT

BACKGROUND: Patients with failed distal femoral megaprostheses often have bone loss that limits reconstructive options and contributes to the high failure rate of revision surgery. The Compress(®) Compliant Pre-stress (CPS) implant can reconstruct the femur even when there is little remaining bone. It differs from traditional stemmed prostheses because it requires only 4 to 8 cm of residual bone for fixation. Given the poor long-term results of stemmed revision constructs, we sought to determine the failure rate and functional outcomes of the CPS implant in revision surgery. QUESTIONS/PURPOSES: (1) What is the cumulative incidence of mechanical and other types of implant failure when used to revise failed distal femoral arthroplasties placed after oncologic resection? (2) What complications are characteristic of this prosthesis? (3) What function do patients achieve after receiving this prosthesis? METHODS: We retrospectively reviewed 27 patients who experienced failure of a distal femoral prosthesis and were revised to a CPS implant from April 2000 to February 2013. Indications for use included a minimum 2.5 mm cortical thickness of the remaining proximal femur, no prior radiation, life expectancy > 10 years, and compliance with protected weightbearing for 3 months. The cumulative incidence of failure was calculated for both mechanical (loss of compression between the implant anchor plug and spindle) and other failure modes using a competing risk analysis. Failure was defined as removal of the CPS implant. Followup was a minimum of 2 years or until implant removal. Median followup for patients with successful revision arthroplasty was 90 months (range, 24-181 months). Functional outcomes were measured with the Musculoskeletal Tumor Society (MSTS) functional assessment score. RESULTS: The cumulative incidence of mechanical failure was 11% (95% confidence interval [CI], 4%-33%) at both 5 and 10 years. These failures occurred early at a median of 5 months. The cumulative incidence of other failures was 18% (95% CI, 7%-45%) at 5 and 10 years, all of which were deep infection. Three patients required secondary operations for cortical insufficiency proximal to the anchor plug in bone not spanned by the CPS implant and unrelated to the prosthesis. Median MSTS score was 27 (range, 24-30). CONCLUSIONS: Revision distal femoral replacement arthroplasty after a failed megaprosthesis is often difficult as a result of a lack of adequate bone. Reconstruction with the CPS implant has an 11% failure rate at 10 years. Our results are promising and demonstrate the durable fixation provided by the CPS implant. Further studies to compare the CPS prosthesis and other reconstruction options with respect to survival and functional outcomes are warranted. LEVEL OF EVIDENCE: Level IV, therapeutic study.


Subject(s)
Bone-Implant Interface , Device Removal , Femoral Neoplasms/surgery , Femur/surgery , Prosthesis Design , Prosthesis Failure , Adolescent , Adult , Biomechanical Phenomena , Disability Evaluation , Female , Femoral Neoplasms/diagnostic imaging , Femoral Neoplasms/physiopathology , Femur/diagnostic imaging , Femur/physiopathology , Humans , Knee Prosthesis , Male , Middle Aged , Osteotomy , Radiography , Recovery of Function , Reoperation , Retrospective Studies , Risk Factors , Stress, Mechanical , Time Factors , Treatment Outcome , Young Adult
18.
Skeletal Radiol ; 44(9): 1317-25, 2015 Sep.
Article in English | MEDLINE | ID: mdl-25982252

ABSTRACT

OBJECTIVE: This study assessed whether radiolucent carbon fiber reinforced-polyetheretherketone (CFR-PEEK) intramedullary nails decreased hardware artifact on magnetic resonance imaging (MRI) and computed tomography (CT) in vitro and in an oncologic patient population. MATERIALS AND METHODS: In vitro and clinical evaluations were done. A qualitative assessment of metal artifact was performed using CFR-PEEK and titanium nail MRI phantoms. Eight patients with a femoral or tibial prophylactic CFR-PEEK nail were retrospectively identified. All patients had postoperative surveillance imaging by MRI, CT, and were followed for a median 20 months (range, 12-28 months). CFR-PEEK images were compared to images from a comparative group of patients with titanium femoral intramedullary nails who had a postoperative MRI or CT. A musculoskeletal-trained radiologist graded visualization of the cortex, corticomedullary junction, and bone-muscle interface, on T1-weighted (T1W), STIR, and contrast-enhanced T1-weighted fat-saturated (T1W FS) sequences of both groups with a five-point scale, performing independent reviews 4 months apart. Statistical analysis used the Wilcoxon rank-sum test and a weighted kappa. RESULTS: Substantially less MRI signal loss occurred in the CFR-PEEK phantom than in the titanium phantom simulation, particularly as the angle increased with respect to direction of the static magnetic field. CFR-PEEK nails had less MRI artifact than titanium nails on scored T1W, STIR, and contrast-enhanced T1W FS MRI sequences (p ≤ 0.03). The mean weighted kappa was 0.64, showing excellent intraobserver reliability between readings. CONCLUSIONS: CFR-PEEK intramedullary nail fixation is a superior alternative to minimize implant artifact on MRI or CT imaging for patients requiring long bone fixation.


Subject(s)
Bone Nails , Carbon/chemistry , Fractures, Bone/diagnosis , Fractures, Bone/surgery , Magnetic Resonance Imaging/methods , Tomography, X-Ray Computed/methods , Adult , Aged , Aged, 80 and over , Benzophenones , Carbon Fiber , Equipment Failure Analysis , Female , Fracture Fixation, Intramedullary/instrumentation , Humans , Image Enhancement/methods , Ketones/chemistry , Male , Middle Aged , Models, Biological , Observer Variation , Polyethylene Glycols/chemistry , Polymers , Postoperative Care/methods , Prognosis , Prosthesis Design , Reproducibility of Results , Retrospective Studies , Sensitivity and Specificity , Titanium , Treatment Outcome
19.
J Shoulder Elbow Surg ; 22(6): 739-44, 2013 Jun.
Article in English | MEDLINE | ID: mdl-23021901

ABSTRACT

BACKGROUND: Patients undergoing revision shoulder arthroplasty frequently have deficient proximal humeral bone stock. Proximal humeral allograft has been recommended to augment reverse total shoulder arthroplasty (RTSA) to improve stability and function. This study reports the results of RTSA without proximal humeral allograft in patients with proximal humeral bone loss secondary to failed shoulder arthroplasty. MATERIALS AND METHODS: From 2005 to 2008, 251 patients were enrolled in a prospective RTSA cohort study. Significant humeral bone loss was demonstrated in 15 of 56 undergoing revision for failed arthroplasty. Average age was 67 years. Average bone loss measured 38.4 mm (range, 26-72 mm). Patients were followed up for a minimum of 2 years with American Shoulder and Elbow Surgeons (ASES), Subjective Shoulder Value (SSV), Constant Score (CS), and visual analog scale (VAS) pain scores, as well as self-reported satisfaction and radiographs. RESULTS: Patients demonstrated significant improvement in mean CS (23.0 to 44.2), ASES (38.2 to 68.3), ASES activities of daily living (7.0 to 15.9), SSV (19.2 to 75.8), and VAS pain (4.6 to 1.6) scores. Thirteen of 15 patients reported satisfaction (87%). Range of motion improved in forward flexion (38.3° to 103.2°) and external rotation (-0.5° to 11.9°). Radiographs demonstrated notching in 3 patients (20%), no humeral subsidence or loosening, and prosthetic fracture of 1 modular humeral stem. CONCLUSIONS: Use of RTSA for failed shoulder arthroplasty and deficient humeral bone stock provides a significant clinical benefit without the need for allograft augmentation. Monoblock humeral component use may diminish risk for prosthetic fracture.


Subject(s)
Arthroplasty, Replacement/methods , Humerus/transplantation , Shoulder Joint/surgery , Activities of Daily Living , Aged , Aged, 80 and over , Allografts , Female , Humans , Joint Instability/prevention & control , Male , Middle Aged , Pain Measurement , Prospective Studies , Prosthesis Design , Range of Motion, Articular , Reoperation , Shoulder Joint/physiopathology , Treatment Failure
20.
Clin Orthop Relat Res ; 467(11): 2813-24, 2009 Nov.
Article in English | MEDLINE | ID: mdl-19662462

ABSTRACT

UNLABELLED: Although functionally appealing in preserving the native knee, the condyle-sparing intercalary allograft of the distal femur may be associated with a higher risk of tumor recurrence and endoprosthetic replacement for malignant distal femoral bone tumors. We therefore compared the risk of local tumor recurrence between patients in these two types of reconstruction groups. We retrospectively reviewed 85 patients (mean age, 22 years; range, 4-82 years), 38 (45%) of whom had a condyle-sparing allograft and 47 (55%) of whom had endoprostheses. The minimum followup for both groups was 2 years (mean, 7 years; range, 2-19 years). Local recurrences occurred in 11% (five of 47) of the patients having implants versus 18% (seven of 38) of the patients having allografts. Using time to local recurrence as an end point, the Kaplan-Meier survivorship of the implant group was similar to that of the condyle-sparing allograft group at 2, 5, and 10 years (93% versus 87% at 2 years, 87% versus 81% at 5 years, and 87% versus 81% at 10 years, respectively). The condyle-sparing allograft procedure offers the potential advantage of retaining the native knee in a young patient population while incurring no greater risk of local recurrence as those offered the endoprosthetic procedure. LEVEL OF EVIDENCE: Level IV, therapeutic study. See Guidelines for Authors for a complete description of levels of evidence.


Subject(s)
Bone Neoplasms/surgery , Bone Transplantation/methods , Femur/surgery , Neoplasm Recurrence, Local/epidemiology , Osteosarcoma/surgery , Prosthesis Implantation/methods , Adolescent , Adult , Aged , Aged, 80 and over , Bone Neoplasms/diagnostic imaging , Bone Neoplasms/mortality , Bone Neoplasms/pathology , Bone Transplantation/adverse effects , Child , Child, Preschool , Cohort Studies , Confidence Intervals , Female , Femur/diagnostic imaging , Femur/pathology , Follow-Up Studies , Humans , Incidence , Kaplan-Meier Estimate , Male , Middle Aged , Neoplasm Recurrence, Local/diagnosis , Odds Ratio , Osteosarcoma/diagnostic imaging , Osteosarcoma/mortality , Osteosarcoma/pathology , Predictive Value of Tests , Prostheses and Implants , Prosthesis Design , Prosthesis Failure , Prosthesis-Related Infections/diagnostic imaging , Prosthesis-Related Infections/epidemiology , Radiography , Plastic Surgery Procedures/methods , Retrospective Studies , Risk Assessment , Survival Analysis , Transplantation, Homologous , Treatment Outcome , Young Adult
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