77 research outputs found
Recurrent Chromosomal Copy Number Alterations in Sporadic Chordomas
The molecular events in chordoma pathogenesis have not been fully delineated, particularly with respect to copy number changes. Understanding copy number alterations in chordoma may reveal critical disease mechanisms that could be exploited for tumor classification and therapy. We report the copy number analysis of 21 sporadic chordomas using array comparative genomic hybridization (CGH). Recurrent copy changes were further evaluated with immunohistochemistry, methylation specific PCR, and quantitative real-time PCR. Similar to previous findings, large copy number losses, involving chromosomes 1p, 3, 4, 9, 10, 13, 14, and 18, were more common than copy number gains. Loss of CDKN2A with or without loss of CDKN2B on 9p21.3 was observed in 16/20 (80%) unique cases of which six (30%) showed homozygous deletions ranging from 76 kilobases to 4.7 megabases. One copy loss of the 10q23.31 region which encodes PTEN was found in 16/20 (80%) cases. Loss of CDKN2A and PTEN expression in the majority of cases was not attributed to promoter methylation. Our sporadic chordoma cases did not show hotspot point mutations in some common cancer gene targets. Moreover, most of these sporadic tumors are not associated with T (brachyury) duplication or amplification. Deficiency of CDKN2A and PTEN expression, although shared across many other different types of tumors, likely represents a key aspect of chordoma pathogenesis. Sporadic chordomas may rely on mechanisms other than copy number gain if they indeed exploit T/ brachyury for proliferation
Malignant Lymphoma of Bone: A Review of 119 Patients
BACKGROUND: Lymphoma of bone is uncommon. As a result of this, many aspects of primary lymphoma of bone (PLB) are controversial: the definition, treatment strategies, response criteria, and prognostic factors. QUESTIONS/PURPOSES: We sought to determine the following in an analysis from a single center over a four-decade period: (1) 5-year disease-free survival of patients with PLB as well as those with systemic lymphoma with bone involvement; and (2) whether prognostic factors (sex, site of tumor, age) were associated with 5-year survival. METHODS: A total of 119 patients with lymphoma involving the musculoskeletal system were retrospectively evaluated. Among these, 94 patients who had a minimum followup of 6 months (mean, 67 months; range, 6 months to 34 years) were further analyzed for the skeletal site of involvement, the orthopaedic intervention(s) needed, and survival. The overall median age was 45 years (range, 7–87 years). The female-to-male ratio was 1:1.53. There were 70 (65 unifocal, five multifocal) patients with PLB. The femur was the most frequent site involved. Appendicular skeleton involvement was substantially higher in patients with PLB. Thirty-four (36%) patients had at least one surgical intervention. Fourteen patients (41%) needed more than one major surgical intervention. RESULTS: The disease-free 5-year survival for patients with PLB was 81% and for the patients with systemic lymphoma with bone involvement, it was 44%. The disease-free 5-year survival of the patients with PLB younger than 60 years old and 60 years old or older was 90% and 62%, respectively. Age was the only prognostic factor on survival of patients with PLB. CONCLUSIONS: Orthopaedic intervention was usually needed for pathologic fractures, avascular necrosis, spinal cord compression, or for the lesions of the weightbearing bones compromising stability or joint motion. The potential for long-term survival suggests the use of implants and techniques that have the best chance of long-term success. LEVEL OF EVIDENCE: Level IV, therapeutic study. See Guidelines for Authors for a complete description of levels of evidence
Clinical Features and Pathobiology of Chordoma
Chordoma is the most common primary malignant bone tumor found in the spine and sacrum. While these tumors are relatively slow growing, they do have the potential to recur and metastasize. Chordoma was described histologically long before it was realized that they were probably derived from notochordal precursor cells. Early reports dating back to Virchow in 1857 describe a vacuolated cell type seen in these tumors. These cells were described as physaliferous, from Greek for “having bubbles.” It was thought at that early time that they were a cartilaginous tumor, which may have been a result of evaluation of a chondroid variant tumor. By 1923, Burrow and Stewart recognized that chordomas were a “lowly malignant tumor of slow growth, locally invasive and destructive, and only rarely giving rise to metastases.” By then, the location at either end of the spine correlated well with contemporary descriptions of the location of vestigial notochordal remnants by Muller. These observations led to the hypothesis that chordomas were not tumors of the intervertebral disc but rather malignant transformation of these notochordal remnants. In 1858, Muller coined the current name by proposing the following hypothesis: “A direct relation of these growths to the chorda dorsalis cannot be overlooked and I consider them to be excessively growing remnants of the chorda. Whosoever likes the name may designate these masses as chordoid tumors, or chordomas.” Since these early descriptions, this concept has been supported by significant indirect evidence, although there is a paucity of direct proof
Abstract 2315: Inhibition of cyclin-dependent kinase 4 as a potential therapeutic strategy for treatment of synovial sarcoma
Abstract Synovial sarcoma is a rare and aggressive form of soft tissue cancer that affects the extremities of the arms or legs, for which current chemotherapeutic agents have not been proven to be very effective. The cyclin-dependent kinase 4/6-retinoblastoma protein (CDK4/6-Rb) pathway is aberrant in a large proportion of cancer. Recent evidences on pre-clinical application of CDK4 inhibitors have been implicated in many types of human cancers, and the FDA has approved the CDK4 selective inhibitor for the treatment of breast cancer. However, the expression and therapeutic potential of CDK4 in synovial sarcoma remain unclear. In the present study, we examined the expression of CDK4 in synovial sarcoma cell lines by western blot and immunofluorescence assay, and in synovial sarcoma tissue microassays by immunohistochemical analysis. Cell viabilities were determined by MTT assay after exposure to different dosages of the selective CDK4 inhibitor. Flow cytometry analysis and wound healing assay were conducted to determine the mechanisms underlying the cytotoxic effects of the selective CDK4 inhibitor. CDK4 specific small interference RNA was used to validate the effect of targeting CDK4 by the selective CDK4 inhibitor in synovial sarcoma cells. We found that CDK4 was highly expressed in human synovial sarcoma, and was related to clinical stage and TNM grade in synovial sarcoma patients and poor prognosis in sarcoma patients. Cell viabilities determined by MTT assay after exposure to different dosages of the selective CDK4 inhibitor showed that this selective CDK4 inhibitor repressed synovial sarcoma cell proliferation and growth in a dose- and time- dependent manner. The selective CDK4 inhibitor inhibited the CDK4/6-Rb signaling pathway and promoted cell apoptosis without influence on the expression of CDK4/6, suggesting that the selective CDK4 inhibitor only repressed the hyperactivation, not the production of CDK4/6. The inhibition effect of the selective CDK4 inhibitor was confirmed by knockdown of CDK4 with specific small interference RNA. Flow cytometry analysis revealed that the selective CDK4 inhibitor induced G1 cell-cycle arrest by targeting CDK4/6-Rb pathway in synovial sarcoma cells. Furthermore, the wound healing assay exhibited that inhibition of CDK4/6-Rb pathway with the use of the selective CDK4 inhibitor significantly decreased synovial sarcoma cell migration in vitro. Our data highlight the role of dysregulated CDK4/6-Rb pathway and current selective CDK4/6 inhibitor may be a potential promising therapeutic agent in the targeted treatment of human synovial sarcoma. Citation Format: Xiaoyang Li, Cassandra Garbutt, Francis John Hornicek, Zhenfeng Duan. Inhibition of cyclin-dependent kinase 4 as a potential therapeutic strategy for treatment of synovial sarcoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 2315
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Upper-extremity infections in patients seropositive for human immunodeficiency virus
The records of 74 human immunodeficiency virus (HIV)-seropositive patients who were treated for upper-extremity infections were retrospectively reviewed. Intravenous drug use was the most common risk factor for HIV infection as well as the most common cause of the infection necessitating admission. These patients were admitted a total of 97 times for the treatment of 89 different infections and underwent 120 surgical procedures. Twenty-six infections (29%) required more than 1 operation, and 11 (12%) resulted in amputation. Twenty-seven patients who met criteria for the diagnosis of acquired immunodeficiency syndrome (AIDS) were found to be no more likely than their HIV-seropositive counterparts to be readmitted for the same diagnosis, to be treated for more than 1 infection, or to require more than 1 oopration or amputation to eradicate their infection. Patients with AIDS were significantly more likely to present with spontaneous onset of infection in the absence of penetrating injury than were those who were HIV seropositive
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Osteoid osteoma: elevation of cardiac and respiratory rates at biopsy needle entry into tumor in 10 patients
To evaluate changes in cardiac and respiratory rates in a consecutive series of patients who underwent percutaneous treatment for lesions presumed to be osteoid osteoma in whom general anesthesia was established.
Changes in cardiac and respiratory rates were evaluated after establishment of stable general anesthesia in 14 patients who underwent needle biopsy and radio-frequency treatment. Cardiac and respiratory rates were recorded at penetration of skin, muscle, periosteum, cortex, and tumor. Treatment was performed before the biopsy report was available.
Biopsy results revealed osteoid osteoma in 10 patients, chondroblastoma in one, and a herniation pit in one. Results in the two remaining patients were nondiagnostic and were excluded. Puncture of skin, muscle, and periosteum caused no detectable change. However, in the 10 patients with biopsy-proved osteoid osteoma, puncture of the tumor caused the mean cardiac rate to increase an average of 26 beats per minute (40%) to 91 (range, 62-114; P <.001) and the mean respiratory rate to increase an average of 12 breaths per minute (50%) to a mean of 37 (range, 25-52; P <.001). These changes occurred within seconds of tumor puncture and were often the first indication to the surgeon that the tumor had been entered. In the two patients with other diagnoses at biopsy, no such change was apparent.
Mean cardiac and respiratory rates increase significantly at needle puncture of osteoid osteoma
Short-term outcomes of cementless modular endoprostheses in lower extremity reconstruction
Background
Modular endoprostheses can be used to reconstruct large osseous defects resulting from tumor resection, trauma, revision arthroplasty, or other causes. They historically have used polymethylmethacrylate cement for fixation to host bone. Newer designs incorporating stems that use cementless bone-ingrowth surfaces have become available, but it is not clear how these compare with cemented designs.
Methods
We performed a retrospective review of all patients treated at our institutions who have had endoprosthetic reconstruction of the proximal femur, distal femur, or proximal tibia using cementless fixation and a single-stem type. The primary outcome was considered to be loosening or reoperation. Thirty-seven cementless modular endoprostheses were implanted in as a subset of endoprostheses used for reconstruction from 2002 through 2007. The decision to use cementless implants and particular stem choice was made by the primary surgeon based upon patient age, diagnosis, prognosis, bone quality, and surgeon experience.
Results
Twenty-two distal femoral, 12 proximal tibial, and two proximal femoral prostheses were implanted, as well as one combined distal femoral and proximal tibial prosthesis, all with the same stem and technique. Kaplan Meier estimated implant survival was 89% at 4 years. Three patients developed loosening of their prosthesis that required revision. There were no periprosthetic fractures or implant breakage in our study.
Conclusions
We demonstrated good short-term outcome of cementless fixation for modular endoprostheses with straight 127-mm stem. The complication rate was relatively low similar to previously reported results of cemented implants
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Introducing and Prospective Efficacy Comparison of an Innovative and Affordable Technique for the Treatment of Distal Radius Fractures
BackgroundThere are different treatments as well as controversies surrounding the adequate treatment for Distal Radius Fractures (DRF). In the absence of enough evidence[HYPHEN]base data regarding clinical effectiveness of available treatments, cost should be considered as an essential factor in selecting the surgical technique for DRF treatment. The goal of this study is introducing an improved and modified pin[HYPHEN]and[HYPHEN]plaster (MP&P) technique as an affordable alternative for treatment of DRF. This study also assesses and compares the outcomes of DRF treatment by using the introduced method versus external fixation (EF) technique.MethodsIn this clinical cohort study, 98 patients presenting with closed DRF Types III or IV, randomly were classified into two modified P&P (50 patients) and EF (48 patients) groups and assessed for functional, clinical, radiographic and overall outcome at the time, 2, 10 and 22 months after surgery. They were also followed[HYPHEN]up for up to 3 years to determine the rate of complications.ResultsEighty one percent of EF and 86% of MP&P group were female. The average ages in the EF and MP&P groups were 44.9 ± 12.4 and 46.1 ± 5.4, respectively. Around 70% of the patients in each group had a Type III fracture, and 30% had Type IV. The rate of complications was higher among EF group patients (seven major and seven minor complications) compared to the MP&P (only 4 minor complications), however the difference between two groups regarding the complications and treatment outcome were insignificant, except in extension ROM and the quick[HYPHEN]dash score (only in two and four months follow up visits) and also returning to work (only in two month follow up visit).ConclusionThis study introduces a modified P&P technique that protects the transverse palmar curvature, prevents the collapse of the distal radius, and simplifies casting, thereby obviating a full arm cast and mitigating elbow stiffness in patient outcomes. This modified technique could be considered as a more cost[HYPHEN]conscious alternative to external fixation for patients with distal radius fractures
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