Abstract:
BACKGROUND:MicroRNAs are small, noncoding RNAs that regulate the expression of posttranslational genes. The presence of some specific microRNAs has been associated with increased risk of both local recurrence and metastasis and worse survival in patients with osteosarcoma. Pathologic fractures in osteosarcoma are considered to be more the manifestation of a neoplasm with a more aggressive biological behavior than the cause itself of worse prognosis. However, this has not been proved at the biological or molecular level. Currently, there has not been a microRNA profiling study of patients who have osteosarcoma with and without pathologic fractures that has described differences in terms of microRNA profiling between these two groups and their correlation with biologic behavior. QUESTIONS/PURPOSES:(1) In patients with osteosarcoma of the extremities, how do the microRNA profiles of those with and without pathologic fractures compare? (2) What relationship do microRNAs have with local recurrence, risk of metastasis, disease-specific survival, and overall survival in osteosarcoma patients with pathologic fractures? METHODS:Between 1994 and 2013, 217 patients were diagnosed and treated at our institution for osteosarcoma of the extremities. Patients were excluded if (1) they underwent oncologic resection of the osteosarcoma at an outside institution (two patients) or (2) they were diagnosed with an extraskeletal osteosarcoma (29 patients) or (3) they had less than 1 year of clinical follow-up and no oncologic outcome (local recurrence, metastasis, or death) (four patients). A total of 182 patients were eligible. Of those, 143 were high-grade osteosarcomas. After evaluation of tumor samples before chemotherapy treatment, a total of 80 consecutive samples were selected for sequencing. Demographic and clinical comparison between the sequenced and non-sequenced patients did not demonstrate any differences, confirming that both groups were comparable. Diagnostic samples from the extremities of 80 patients with high-grade extremity osteosarcomas who had not yet received chemotherapy underwent microRNA sequencing for an ongoing large-scale osteosarcoma genome profiling project at our institution. Six samples were removed after a second look by a musculoskeletal pathologist who verified cellularity and quality of samples to be sequenced, leaving a total of 74 patients. Of these, two samples were removed as they were confirmed to be pelvic tumors in a second check after sequencing. The final study sample was 72 patients (11 patients with pathologic fractures and 61 without). Sequencing data were correlated with fractures and local recurrence, risk of metastasis, disease-specific survival, and overall survival through Kaplan-Meier analyses. RESULTS:Several microRNAs were expressed differently between the two groups. Among the markers with the highest differential expression (edgeR and DESeq algorithms), Hsa-mIR 656-3p, hsa-miR 493-5p, and hsa-miR 381-3p were upregulated in patients with pathologic fractures, whereas hsa-miR 363, hsa-miR 885-5p, and has-miR 20b-5p were downregulated. The highest differential expression fracture and nonfracture-associated microRNA markers also distinguished groups of patients with different metastasis risk, a well as different disease-specific and overall survival. Furthermore, the profile of pathologic fractures demonstrated a higher differential expression for microRNA markers that were previously associated with a higher risk of metastasis and lower survival rates in patients with osteosarcoma. CONCLUSIONS:In patients who have osteosarcoma, the microRNA profiles of those with pathologic fractures are different than of patients without pathologic fractures. The highest differential expression mircroRNA molecules in patients with pathologic fractures predict also higher risk of metastatic disease as well as worse disease-specific survival and overall survival. Furthermore, we found higher differential expression of microRNAs in the pathologic fracture group previously associated with poor prognosis. The higher risk of metastasis and poorer overall survival in patients with pathologic fractures is inherent to tumor aggressive biologic behavior. It is plausible that the fracture itself is not the direct cause of worse prognosis but another manifestation of tumor biologic aggressiveness. Identification of these molecules through liquid biopsies may help to determine which patients may benefit from surgery before fractures occur. The same technology can be applied to identify patterns of response to conventional chemotherapy, assisting in more specific and accurate systemic therapy. LEVEL OF EVIDENCE LEVEL:III, prognostic study.
journal_name
Clin Orthop Relat Resjournal_title
Clinical orthopaedics and related researchauthors
Lozano Calderón SA,Garbutt C,Kim J,Lietz CE,Chen YL,Bernstein K,Chebib I,Nielsen GP,Deshpande V,Rubio R,Wang YE,Quackenbush J,Delaney T,Raskin K,Schwab J,Cote G,Spentzos Ddoi
10.1097/CORR.0000000000000867subject
Has Abstractpub_date
2019-09-01 00:00:00pages
2114-2126issue
9eissn
0009-921Xissn
1528-1132journal_volume
477pub_type
杂志文章abstract:BACKGROUND:Earlier results with porous tantalum acetabular cups in revision THA generally have been favorable. Recently there has been some evidence presented that porous tantalum cups might decrease the risk of rerevision in the setting of revision hip surgery performed owing to prosthetic joint infection (PJI). As th...
journal_title:Clinical orthopaedics and related research
pub_type: 杂志文章,多中心研究
doi:10.1007/s11999-017-5417-3
更新日期:2017-12-01 00:00:00
abstract::Paget's disease of bone in 51 patients was treated with ethane-1, hydroxy-1,1 diphosphonate (EHDP) for six months at a dosage of 5 mg/kg/day. Clinically, the analgesic effect on bone pain is clear, with parallel reduction in radioisotope uptake observed by quantitative bone scintigraphy. There is also a reduction of a...
journal_title:Clinical orthopaedics and related research
pub_type: 杂志文章
doi:
更新日期:1983-04-01 00:00:00
abstract:BACKGROUND:Cancer and spinal surgery are both considered risk factors for venous thromboembolism (VTE). However, the risk of symptomatic VTE for patients undergoing surgery for spine metastases remains undefined. QUESTIONS/PURPOSES:The purposes of this study were to: (1) identify the proportion of patients who develop...
journal_title:Clinical orthopaedics and related research
pub_type: 杂志文章
doi:10.1097/CORR.0000000000000733
更新日期:2019-07-01 00:00:00
abstract::In a retrospective study, 14,731 menisci were examined to determine the incidence of discoid medial and lateral menisci. Of 8040 medial menisci, ten (0.12%) were discoid. Of 6691 lateral menisci, 102 (1.5%) were discoid. Only 22 discoid medial menisci have been reported in the medical literature. The previously report...
journal_title:Clinical orthopaedics and related research
pub_type: 杂志文章
doi:
更新日期:1982-08-01 00:00:00
abstract::Surgical fusion may be indicated to stabilize deformed or painful hindfoot joints. Although more commonly performed in children or adolescents, it is the salvage procedure available for adults. Twenty-six patients (30 feet; 20 women, six men) followed for an average of 44.1 months after hindfoot arthrodesis were inves...
journal_title:Clinical orthopaedics and related research
pub_type: 杂志文章
doi:
更新日期:1990-08-01 00:00:00
abstract:BACKGROUND:Bone quality should play an important role in decision-making for orthopaedic treatment options, implant selection, and affect ultimate surgical outcomes. The development of decision-making tools, currently typified by clinical guidelines, is highly dependent on the precise definition of the term(s) and the ...
journal_title:Clinical orthopaedics and related research
pub_type: 杂志文章,评审
doi:10.1007/s11999-011-1838-6
更新日期:2011-08-01 00:00:00
abstract::A long-term review of 272 resections of the metatarsal heads and bases of the phalanges in 128 patients with severe rheumatoid feet is presented. The longest follow-up is 11 years and the average follow-up was 4.7 years. Recurrent deformity and callus formation was usually due to a long metatarsal shaft. The operation...
journal_title:Clinical orthopaedics and related research
pub_type: 杂志文章
doi:10.1097/00003086-197505000-00036
更新日期:1975-05-01 00:00:00
abstract:BACKGROUND:There is growing interest in value-based health care in the United States. Statistical analysis of large databases can inform us of the factors associated with and the probability of adverse events and unplanned readmissions that diminish quality and add expense. For example, increased operating time and hig...
journal_title:Clinical orthopaedics and related research
pub_type: 杂志文章
doi:10.1007/s11999-016-5147-y
更新日期:2017-12-01 00:00:00
abstract::Glucocorticoid injection is widely used in tendon disorders. Despite previous studies on the histologic and biomechanical changes in tendons after glucocorticoid injections, the role of glucocorticoid in tendon rupture still is controversial. It was hypothesized that glucocorticoid has a direct deleterious effect on h...
journal_title:Clinical orthopaedics and related research
pub_type: 杂志文章
doi:10.1097/01.blo.0000118184.83983.65
更新日期:2004-04-01 00:00:00
abstract:BACKGROUND:Arthroplasty for shoulder fractures is a technically challenging and unpredictable procedure and its use is controversial. QUESTIONS/PURPOSES:We therefore asked (1) to what degree function would be restored, (2) whether tuberosity healing would reliably occur, and (3) whether stem design would influence fun...
journal_title:Clinical orthopaedics and related research
pub_type: 杂志文章
doi:10.1007/s11999-011-1919-6
更新日期:2011-12-01 00:00:00
abstract:BACKGROUND:Osteosarcoma is the most common type of bone cancer in adolescents. There have been no significant improvements in outcomes since chemotherapy was first introduced. Bupivacaine and lidocaine have been shown to be toxic to certain malignancies. This study evaluates the effect of these medications on two osteo...
journal_title:Clinical orthopaedics and related research
pub_type: 杂志文章
doi:10.1097/CORR.0000000000001510
更新日期:2021-01-01 00:00:00
abstract:UNLABELLED:Because of improvements in surgical technique, anesthesia, and rehabilitation, mortality after hip arthroplasty may be on the decline. The purpose of this study was to determine the 90-day mortality rate after uncemented total hip arthroplasty (THA) performed under regional anesthesia. We retrospectively rev...
journal_title:Clinical orthopaedics and related research
pub_type: 杂志文章
doi:10.1007/s11999-008-0528-5
更新日期:2009-01-01 00:00:00
abstract::This study evaluates the role of magnetic resonance imaging in assessing the factors affecting the rate and healing time in scaphoid nonunions after surgery. Nineteen patients were assessed before surgery by radiographs, tomography, and magnetic resonance imaging. Fifteen had viable bone marrow and 4 patients had nonv...
journal_title:Clinical orthopaedics and related research
pub_type: 杂志文章
doi:10.1097/00003086-199703000-00032
更新日期:1997-03-01 00:00:00
abstract::The acute and repetitive impact and torsional joint loading that occurs during participation in sports can damage articular surfaces causing pain, joint dysfunction, and effusions. In some instances, this articular surface damage leads to progressive joint degeneration. Three classes of chondral and osteochondral inju...
journal_title:Clinical orthopaedics and related research
pub_type: 杂志文章,评审
doi:10.1097/00003086-200209000-00004
更新日期:2002-09-01 00:00:00
abstract::Bone tumors occurring in periarticular locations may cause a substantial risk of subchondral fracture and collapse. Poly-methylmethacrylate has been used for reconstruction in these instances because of its immediate structural stability. Allogeneic graft allows for biologic incorporation and remodeling, but it takes ...
journal_title:Clinical orthopaedics and related research
pub_type: 杂志文章
doi:10.1097/blo.0b013e31804e8470
更新日期:2007-08-01 00:00:00
abstract:BACKGROUND:In clinical trials of THA, model-based radiostereometric analysis (RSA) techniques may be less precise than conventional marker-based RSA for measurement of femoral stem rotation. We verified the accuracy and clinical precision of RSA based on computer-aided design models of a cementless tapered wedge femora...
journal_title:Clinical orthopaedics and related research
pub_type: 临床试验,杂志文章
doi:10.1007/s11999-016-4930-0
更新日期:2016-10-01 00:00:00
abstract:BACKGROUND:As a generic measure of health-related quality of life among patients awaiting THA or TKA, the three-level version of the EQ-5D (EQ-5D-3L), which has three response levels of severity (no problems, some problems, and extreme problems/unable) to five questions, is widely used. Previous studies indicated that ...
journal_title:Clinical orthopaedics and related research
pub_type: 杂志文章
doi:10.1097/CORR.0000000000000662
更新日期:2019-07-01 00:00:00
abstract::Patients with shoulder arthritis present to the orthopedic surgeon due to joint pain and loss of shoulder motion. A differential diagnosis is established, based on the history and physical examination and selected laboratory tests and roentgenograms. Synovial fluid analysis is often very helpful in the diagnosis of sh...
journal_title:Clinical orthopaedics and related research
pub_type: 杂志文章
doi:
更新日期:1983-03-01 00:00:00
abstract::The Short Form 36, The Toronto Extremity Salvage Score, and the 1987 and 1993 Musculoskeletal Tumor Society Rating Scales were compared as measures of functional status for patients with lower extremity sarcoma. The study included 97 patients with lower extremity sarcoma and evaluated each measure on the following mea...
journal_title:Clinical orthopaedics and related research
pub_type: 杂志文章
doi:
更新日期:1999-01-01 00:00:00
abstract::The treatment program after anterior cruciate ligament (ACL) injury or reconstruction at the United States Military Academy embraces the four cornerstones of rehabilitation--strength, aerobic fitness, coordination, and confidence. It is divided into six phases--presurgery, to prepare the patient for postoperative reha...
journal_title:Clinical orthopaedics and related research
pub_type: 杂志文章
doi:
更新日期:1983-01-01 00:00:00
abstract:BACKGROUND:Cementless fixation remains controversial in TKA due to the challenge of achieving consistent skeletal attachment. Factors predicting durable fixation are not clearly understood, but we presumed bone ingrowth could be enhanced by the quantity of host bone and application of autograft bone chips. QUESTIONS/P...
journal_title:Clinical orthopaedics and related research
pub_type: 杂志文章
doi:10.1007/s11999-011-2214-2
更新日期:2012-07-01 00:00:00
abstract:BACKGROUND:Radial head alignment is the key to determine elbow reduction after treatment of subluxations or Monteggia fractures. The radiocapitellar ratio (RCR) quantifies the degree of subluxation, by evaluating radial head alignment with the capitellum of the humerus; this ratio is reproducible when measured on true ...
journal_title:Clinical orthopaedics and related research
pub_type: 杂志文章
doi:10.1007/s11999-013-3027-2
更新日期:2013-08-01 00:00:00
abstract::Femoral head collapse occurred in a 20-year-old ballet dancer with anorexia nervosa. The patient developed anorexia nervosa at the age of 11 years and had short stature. The condition never resolved, and she developed pain and stiffness in the right hip at the age of 18 years, with documentation of femoral head collap...
journal_title:Clinical orthopaedics and related research
pub_type: 杂志文章
doi:
更新日期:1990-02-01 00:00:00
abstract::Intramedullary nailing after reaming of the medullary cavity according to Küntscher, provides a rigid fixation and makes early mobilization possible, and is even applicable to infected non-unions. Experience with 150 cases of fresh femoral fractures and more than 80 cases of non-union of the femur, the tibia, the hume...
journal_title:Clinical orthopaedics and related research
pub_type: 杂志文章
doi:
更新日期:1976-03-01 00:00:00
abstract::After reviewing a series of 220 patients operated upon between 1975 and 1985 for traumatic brachial plexus injuries, the authors present the results of 103 myelographies, 48 computed tomographies (CT scans) combined with standard myelography, and 25 series of images obtained by magnetic resonance imaging (MRI). To eva...
journal_title:Clinical orthopaedics and related research
pub_type: 杂志文章
doi:
更新日期:1988-12-01 00:00:00
abstract::The treatment of osteonecrosis of the hip remains a dilemma. Contemporary basic science research focuses on establishing the molecular etiology of this disease with the hope of identifying targets for pharmacologic intervention. Researchers have identified specific genetic polymorphisms that may predispose its develop...
journal_title:Clinical orthopaedics and related research
pub_type: 杂志文章,评审
doi:10.1097/BLO.0b013e3181591c92
更新日期:2007-12-01 00:00:00
abstract::Both total knee alignment methods, the anatomic and classic, seek to achieve stability in flexion and extension. However, posterior femoral condyle referencing (anatomic alignment) combined with perpendicular tibial resection (classic alignment) results in a 3 degree relative internal rotation of the femoral component...
journal_title:Clinical orthopaedics and related research
pub_type: 杂志文章
doi:10.1097/00003086-200201000-00029
更新日期:2002-01-01 00:00:00
abstract::Successful placement of the distal interlocking screws into the Grosse-Kempf nail is a demanding procedure due in part to deformation of the nail during insertion and to inaccuracy of the targeting device supplied with the system. The authors suggest an alternative approach. After placement of the nail in a tibia or f...
journal_title:Clinical orthopaedics and related research
pub_type: 杂志文章
doi:
更新日期:1989-01-01 00:00:00
abstract::The magnetic resonance (MR) signal behavior of freshly excised pig femoral heads undergoing ischemic necrosis in vitro was evaluated. Ten femoral heads removed from skeletally immature pigs were stored at 37 degrees in a sealed, sterile container during the observation period. Imaging was initially performed 40 minute...
journal_title:Clinical orthopaedics and related research
pub_type: 杂志文章
doi:
更新日期:1989-07-01 00:00:00
abstract::Seventy-five adults who sustained 76 tibial plateau fractures were treated according to a prospective protocol using instability in extension as the principal indication for operative fixation. Patients showing instability underwent closed manipulative reduction under fluoroscopic guidance. If significant joint depres...
journal_title:Clinical orthopaedics and related research
pub_type: 杂志文章
doi:10.1097/00003086-199706000-00007
更新日期:1997-06-01 00:00:00