Minimally invasive stabilization of pelvic metastatic bone disease: A review of an emerging technique.

Percutaneous pelvic stabilization is an emerging technique that provides mechanical stability to pathologic fractures of the pelvic ring and acetabulum. Variability exists in procedural technique among institutions; however, early case series consistently demonstrate an acceptable complication profile and significant improvement in patients' pain and function. This minimally invasive approach is less morbid than traditional, open acetabular and pelvic reconstructions. Therefore, this procedure is an encouraging palliative intervention for a growing patient population in need.

Minimally invasive management of pathologic fractures of the pelvis and sacrum: Tumor ablation and fracture stabilization.

BACKGROUND: Pathologic fractures of the pelvis/sacrum due to metastatic bone disease (MBD) cause pain and dysfunction due to mechanical instability of the pelvic ring. This study presents our multi-institutional experience with percutaneous stabilization of pathologic fractures and osteolytic lesions from MBD throughout the pelvic ring. METHODS: The records of patients undergoing this procedure from 2018 to 2022 were reviewed retrospectively from two institutions. Surgical data and functional outcomes were recorded. RESULTS: Fifty-six patients underwent percutaneous stabilization, with a median operative duration of 119 min (interquartile range [IQR]: 92.8, 167) and median estimated blood loss of 50 mL (IQR: 20, 100). The median length of stay was 3 days (IQR: 1, 6), and 69.6% (n = 39) of patients were discharged home. Early complications included one partial lumbosacral plexus injury, three acute kidney injuries, and one case of intra-articular cement extravasation. Late complications included two infections and one revision stabilization procedure for hardware failure. Mean Eastern Cooperative Oncology Group (ECOG) scores improved from 3.02 (SD 0.8) preoperatively to 1.86 (SD 1.1) postoperatively (p < 0.001). Ambulatory status also improved (p < 0.001). CONCLUSIONS: Percutaneous stabilization of pathologic fractures and osteolytic defects of the pelvis and sacrum is a procedure that improves patient function, ambulatory status and is associated with a limited complication profile.

A Novel Method to Prevent Terminal Appositional Overgrowth Following Pediatric Below Knee Amputations A Case Series and Review of the Literature.

The terminal overgrowth of the tibia following pediatric transtibial amputation is a common problem leading to pain, disability, and repeat surgical procedures. We present three patients who underwent transtibial amputation due to sarcoma of the lower extremity followed by compress osseointegration prosthesis fixation. The minimum follow-up was 1 year. The average age of patients was 10.8 years. There were no complications that required surgical revision. To date, there has been no evidence of terminal appositional overgrowth in this series. The application of an end-cap implant utilizing compressive osseointegration fixation can prevent terminal bone overgrowth in pediatric transtibial amputations.

PROMIS® scores in operative metastatic bone disease patients: A multicenter, prospective study.

BACKGROUND: The prevalence of metastatic bone disease (MBD) grows each year as treatments improve. Little has been published about functional and pain outcomes in this group after surgery. Patient-Reported Outcomes Measurement Information System (PROMIS® ) can collect information, in just minutes, about patient's physical, mental, and social health. This study evaluated PROMIS® pain and functional scores in surgically treated patients with MBD. METHODS: Basic demographics and PROMIS® scores were recorded from a total of 13 patients at 9 periods of time over 6 months. RESULTS: The average change in physical function at week 1 was -2.5 (standard deviation [SD] = 5.4), at 2 weeks 1.7 (SD = 7.6), after 4 weeks 6.9 (SD = 10), after 6 weeks 6.4 (SD = 10.9), after 10 weeks 15.3 (SD = 3.1), and after 3 months 8.6 (SD = 7.6). The average change in pain inference at week 1 was -1.2 (SD = 7.3), at 2 weeks -2.1 (SD = 9.5), after 4 weeks -12.6 (SD = 4.5), after 6 weeks -8.3 (SD = 10.2), after 10 weeks -16.6 (SD = 4.3), and after 3 months -11.4 (SD = 8.2). CONCLUSIONS: PROMIS® provides a feasible means to collect data in this population. Trends of improved function and decreased pain were seen after surgery. Continuing this study will hopefully elucidate more insight into the surgical treatment of MBD.

Limb Salvage Versus Amputation in Conventional Appendicular Osteosarcoma: a Systematic Review.

The overall survivorship in patients with appendicular osteosarcoma has increased in the past few decades. However, controversies and questions about performing an amputation or a limb salvage procedure still remain. Using three peer-reviewed library databases, a systematic review of the literature was performed to evaluate all studies that have evaluated the outcomes of appendicular osteosarcoma, either with limb salvage or amputation. The mean 5-year overall survivorship was 62% for salvage and 58% for amputation (p > 0.05). At mean 6-year follow-up, the local recurrence rates were 8.2% for salvage and 3.0% for amputation (p > 0.05). Additionally, at mean 6-year follow-up, the rate for metastasis was 33% for salvage and 38% for amputation (p > 0.05). The revision rates were higher with salvage (31 vs. 28%), and there were more complications in the salvage groups (52 vs. 34%; p > 0.05). Despite the heterogeneity of studies available for review, we observed similar survival rates between the two procedures. Although there was no significant statistical difference between rates of recurrence and metastasis, the local recurrence rate and risk of complications were higher for limb salvage as compared to amputation. Cosmetic satisfaction is often higher with limb salvage, whereas long-term expense is higher with amputation. Overall, current literature supports limb salvage procedures when wide surgical margins can be achieved while still retaining a functional limb.

The Impact of Microenvironment on the Synovial Sarcoma Transcriptome.

Synovial sarcoma (SS) is initiated by a t(X;18) chromosomal translocation and resultant SS18-SSX fusion oncogene. Only a few SS cell lines exist. None has been compared to its source tumor. In order to compare matched tumor and cell line pairs, we performed RNAseq on 3 tumor/cell line pairs from a genetically engineered mouse model of SS, as well as 2 pairs from human SS tumors. Transcriptomes of mouse tumors and derivative cell lines deviated significantly. Differentially expressed genes highlighted inflammatory infiltrates and metabolism. The same was found for the human tumor and cell line pairs. More was shared between different tumors than between any tumor and its cell line. Direct xenografting generated transcriptomes that more closely resembled the primary tumor than did its derivative cell line. SS tumor transcriptomes are powerfully impacted by the environment wherein they reside, especially with regard to immune interaction and metabolism.

Use of Compressive Osseointegration Endoprostheses for Massive Bone Loss From Tumor and Failed Arthroplasty: A Viable Option in the Upper Extremity.

BACKGROUND: Endoprostheses using principles of compressive osseointegration have shown good survivorship in several studies involving the lower extremity; however, no series to our knowledge have documented the use of this technology in the management of massive bone loss in the upper limb. QUESTIONS/PURPOSES: (1) What proportion of upper extremity implants using compressive osseointegration fixation principles achieved durable short-term fixation, and what were the modes of failure? (2) What surgical complications resulted from reconstruction using this technique? METHODS: A multiinstitutional retrospective review identified nine patients (five women; four men) who underwent 13 endoprosthetic replacements between 2003 and 2014 using compressive osseointegration (Compliant® Pre-stress Device [CPS]; Biomet Inc, Warsaw, IN, USA) in the upper extremity, including two proximal humeri, two humeral diaphyses, seven distal humeri, and two proximal ulna. During the early part of that period, the indication for use of a compressive prosthesis in our centers was revision of a previous tumor reconstruction (allograft-prosthetic composite or stemmed endoprosthetic reconstruction) (three patients; five implants), or revision arthroplasty with massive bone loss (three patients, four implants); more recently, indications became somewhat more permissive and included posttraumatic bone loss (one patient, one implant), primary bone sarcoma, and resections with very short remaining end segments after diaphyseal resections (two patients, three implants). Minimum followup was 24 months; one patient (one implant) was lost to followup before that time with the implant intact at 14 months and no patients have died. The mean age of the patients was 45 years (range, 21-62 years). Mean followup was 68 months (range, 24-141 months). Implant revision for any cause and for failure of the CPS mechanism was recorded. Modes of failure were categorized as soft tissue, aseptic loosening, structural, infection, and tumor progression; CPS modes of failure were defined as lack of fixation, with or without bone or implant fracture. RESULTS: Of the 12 implants accounted for beyond 2 years, six had undergone revision of any kind. Only two revisions in two patients were attributable to lack of CPS fixation at the bone-implant interface; one of the patients also had periprosthetic and implant fracture develop through the traction bar. Other modes of failure were aseptic loosening of the standard ulnar component (two patients, two implants), bushing wear (one patient; one implant) and infection resulting in two-stage exchange and free soft tissue transfer with retention of the CPS spindle (one patient, one implant). Complications for all nine patients included one transient radial nerve palsy, one ulnar nerve sensory neurapraxia, one superficial infection, and two glenohumeral subluxations, one underwent revision surgery with implantation of a constrained liner. CONCLUSIONS: A compressive osseointegration endoprosthesis is an option for very difficult revisions or sarcoma resection in the upper extremity in which the remaining segment of host bone is too short for a conventional prosthesis. However, surgeons must inform patients that these are salvage operations, and revision surgery is common. Long-term followup of more patients is necessary to further document the survivorship of these implants in the upper extremity. LEVEL OF EVIDENCE: Level IV, therapeutic study.

Has the Level of Evidence of Podium Presentations at the Musculoskeletal Tumor Society Annual Meeting Changed Over Time?

BACKGROUND: Level of evidence (LOE) framework is a tool with which to categorize clinical studies based on their likelihood to be influenced by bias. Improvements in LOE have been demonstrated throughout orthopaedics, prompting our evaluation of orthopaedic oncology research LOE to determine if it has changed in kind. QUESTIONS/PURPOSES: (1) Has the LOE presented at the Musculoskeletal Tumor Society (MSTS) annual meeting improved over time? (2) Over the past decade, how do the MSTS and Orthopaedic Trauma Association (OTA) annual meetings compare regarding LOE overall and for the subset of therapeutic studies? METHODS: We reviewed abstracts from MSTS and OTA annual meeting podium presentations from 2005 to 2014. Three independent reviewers evaluated a total of 1222 abstracts for study type and LOE; there were 577 abstracts from MSTS and 645 from OTA. Changes in the distributions of study type and LOE over time were evaluated by Pearson chi-square test. RESULTS: There was no change over time in MSTS LOE for all study types (p = 0.13) and therapeutic (p = 0.36) study types during the reviewed decade. In contrast, OTA LOE increased over this time for all study types (p < 0.01). The proportion of Level I therapeutic studies was higher at the OTA than the MSTS (3% [14 of 413] versus 0.5% [two of 387], respectively), whereas the proportion of Level IV studies was lower at the OTA than the MSTS (32% [134 of 413] versus 75% [292 of 387], respectively) during the reviewed decade. The proportion of controlled therapeutic studies (LOE I through III) versus uncontrolled studies (LOE IV) increased over time at OTA (p < 0.021), but not at MSTS (p = 0.10). CONCLUSIONS: Uncontrolled case series continue to dominate the MSTS scientific program, limiting progress in evidence-based clinical care. Techniques used by the OTA to improve LOE may be emulated by the MSTS. These techniques focus on broad participation in multicenter collaborations that are designed in a comprehensive manner and answer a pragmatic clinical question.

Is Prophylactic Intervention More Cost-effective Than the Treatment of Pathologic Fractures in Metastatic Bone Disease?

BACKGROUND: Metastatic bone disease is a substantial burden to patients and the healthcare system as a whole. Metastatic disease can be painful, is associated with decreased survival, and is emotionally traumatic to patients when they discover their disease has progressed. In the United States, more than 250,000 patients have metastatic bone disease, with an estimated annual cost of USD 12 billion. Prior studies suggest that patients who receive prophylactic fixation for impending pathologic fractures, compared with those treated for realized pathologic fractures, have decreased pain levels, faster postoperative rehabilitation, and less in-hospital morbidity. However, to our knowledge, the relative economic utility of these treatment options has not been examined. QUESTIONS/PURPOSES: We asked: (1) Is there a cost difference between a cohort of patients treated surgically for pathologic fractures compared with a cohort of patients treated prophylactically for impending pathologic lesions? (2) Do these cohorts differ in other ways regarding their utilization of healthcare resources? METHODS: We performed a retrospective study of 40 patients treated our institution. Between 2011 and 2014, we treated 46 patients surgically for metastatic lesions of long bones. Of those, 19 (48%) presented with pathologic fractures; the other 21 patients (53%) underwent surgery for impending fractures. Risk of impending fracture was determined by one surgeon based on appearance of the lesion, subjective symptoms of the patient, cortical involvement, and location of the lesion. At 1 year postoperative, four patients in each group had died. Six patients (13%) were treated for metastatic disease but were excluded from the retrospective data because of a change in medical record system and inability to obtain financial records. Variables of interest included total and direct costs per episode of care, days of hospitalization, discharge disposition, 1-year postoperative mortality, and descriptive demographic data. All costs were expressed as a cost ratio between the two cohorts, and total differences between the groups, as required per medical center regulations. All data were collected by one author and the medical center's financial office. RESULTS: Mean total cost was higher in patients with pathologic fractures (cost unit [CU], 642 ± 519) than those treated prophylactically without fractures (CU, 370 ± 171; mean difference, 272; 95% CI, 19-525; p = 0.036). In USD, this translates to a mean of nearly USD 21,000 less for prophylactic surgery. Mean direct cost was 41% higher (nearly USD 12,000) in patients with a pathologic fracture (CU, 382 ± 300 versus 227 ± 93; mean difference, 155; 95% CI, 9-300; p = 0.038). Mean length of stay was longer in patients with pathologic fractures compared with the group treated prophylactically (8 ± 6 versus 4 ± 3 days; mean difference, 4; 95% CI, 1-7; p = 0.01). CONCLUSIONS: These findings show economic and clinical value of prophylactic stabilization of metastatic lesions when performed for patients with painful lesions compromising the structural integrity of long bones. Patients sustaining a pathologic fracture may represent a more severe, sicker demographic than patients treated for impending pathologic lesions. LEVEL OF EVIDENCE: Level IV, economic and decision analysis.

Identification of Risk Factors for Acute Surgical Site Infections in Musculoskeletal Tumor Patients Using CDC/NHSN Criteria.

BACKGROUND: Acute surgical site infections (SSI) are well-recognized postoperative complications, representing a significant source of patient morbidity and cost to the healthcare system. This study is among the first to use standardized criteria for the diagnosis of acute SSI in orthopaedic oncology. METHODS: The medical records of 165 patients were retrospectively reviewed for the occurrence of superficial or deep SSI as defined by the Center for Disease Control's National Healthcare Safety Network (CDC/NHSN) criteria. Patient, disease, and procedure-specific variables were evaluated as potential risk factors for infection. RESULTS: The overall rate of acute SSI was 10.3%. Univariate analysis demonstrated the significance of malignant pathology (p < 0.001), ASA classification (p = 0.009), operative duration (p < 0.001), intraoperative RBC transfusions (p = 0.03), the performance of an amputation (p = 0.016), and race (p = 0.008) on the incidence of SSI. Prolonged operative duration (p = 0.014) and race (p = 0.005) were found to be independent risk factors with odds ratios of 1.89 (95%, CI: 1.14 to 3.14) and 0.047 (95%, CI: 0.006 to 0.387), respectively. CONCLUSIONS: By using the CDC/NHSN guidelines for the diagnosis of acute SSI, we identified prolonged operative time and non-Caucasian race as independent risk factors for infection in musculoskeletal tumor patients.

Minimizing Blood Loss in Orthopaedic Surgery The Role of Antifibrinolytics.

Many common orthopaedic procedures are associated with a large volume of blood loss. Antifibrinolytics have a well-elucidated mechanism of action and a long history of clinical use. By inhibiting the enzymatic breakdown of fibrin, there has been a demonstrated ability to decrease total blood loss and reduce postoperative transfusion requirements. Despite substantial use in cardiac surgery, antifibrinolytic use in orthopaedic surgery has been limited due to concerns over the potential for venous thromboembolism. A growing body of evidence demonstrates the medications' efficacy and safety in arthroplasty and spine surgery. Due to the risks associated with allogenic blood transfusions and the limitations of alternative blood conservation strategies, antifibrinolytics are a reasonable strategy in blood conservation programs for patients undergoing major orthopaedic procedures.

Tumoral TP53 and/or CDKN2A alterations are not reliable prognostic biomarkers in patients with localized Ewing sarcoma: a report from the Children's Oncology Group.

BACKGROUND: A growing collection of retrospective studies have suggested that TP53 mutations and/or CDKN2A deletions have prognostic significance in Ewing sarcoma. We sought to evaluate these variables in patients with localized disease treated prospectively on a single Children's Oncology Group protocol. PROCEDURE: Of the 568 patients enrolled on Children's Oncology Group protocol AEWS0031 (NCT00006734), 112 had tumor specimens of sufficient quality and quantity to allow for analysis of TP53 mutations status by DNA sequencing, and CDKN2A deletion by dual color fluorescent in situ hybridization. RESULTS: Eight of 93 cases (8.6%) were found to have TP53 point mutations and 12 of 107 cases (11.2%) demonstrated homozygous CDKN2A deletion. Two cases were found to have an alteration in both genes. There was no significant difference in event-free survival of patients with TP53 mutations and/or CDKN2A deletions compared to patients with normal TP53/CDKN2A gene status, as demonstrated by log rank test (p = 0.58). CONCLUSIONS: Although previous retrospective studies suggest their significance, TP53 mutation and/or CDKN2A deletion are not reliable prognostic biomarkers in localized Ewing sarcoma.

Novel applications of osseointegration in orthopedic limb salvage surgery.

Osseointegration is a biologic process vital to modern endoprosthetic fixation in orthopedic surgery. Numerous engineering advancements have improved the utilization of this technology in orthopedics; however, issues such as stress shielding, aseptic loosening, and bone loss remain an ongoing challenge. These host responses are especially problematic in limb salvage surgery. Novel applications of osseointegration have been developed to address some of these fixation issues with massive tumor endoprostheses. This articles reviews osseointegration and emerging novel applications of this technology in limb salvage surgery and future prosthetics for amputees.

Local control of metastatic sarcoma.

PURPOSE OF REVIEW: Survival rates for children with metastatic sarcoma have remained dismal despite intensified multiagent chemotherapy protocols. The local treatment of metastatic disease has been promoted as a way to eliminate colonies of genetically unstable, heterogeneous metastatic cells in an attempt to improve survival amongst this most unfortunate patient population. RECENT FINDINGS: The survival benefit offered by pulmonary metastasectomies in patients with metastatic osteosarcoma is well substantiated. Utilization of other local treatment modalities, such as radiation therapy and percutaneous thermal ablation, offers the opportunity to intervene in a wide range of pulmonary and extrapulmonary metastatic disease. Patients who have the entirety of their identifiable disease addressed by local control modalities consistently demonstrate improved survival compared with patients who are treated with systemic therapy in isolation. SUMMARY: The current state of the literature prevents a definitive conclusion about the utility of local control for metastatic sarcoma. The retrospective trials are clouded by selection bias and the prospective studies are designed to address alternative questions. However, the techniques utilized for local control impart minimal risk to the patient and, in amenable cases, have been shown to provide an opportunity to effect a cure in children with an otherwise dismal prognosis.

Identification of a novel membrane-associated gene product that suppresses toxicity of a TrfA peptide from plasmid RK2 and its relationship to the DnaA host initiation protein.

The toxicity of a peptide derived from the amino-terminal portion of 33-kDa TrfA, one of the initiation proteins encoded by the broad-host-range plasmid RK2, was suppressed by a host protein related to DnaA, the initiation protein of Escherichia coli. The newly identified 28.4-kDa protein, termed a DnaA paralog (Dp) because it is similar to a region of DnaA but likely has a different function in initiation of plasmid RK2 replication, interacts physically with the 33-kDa TrfA initiation protein, including the initiation-active monomeric form. The Dp has a cellular distribution similar to that of the 33-kDa TrfA initiation protein, being found primarily in the inner membrane fraction, with lesser amounts detected in the outer membrane fraction and almost none in the soluble fraction of E. coli. Maintenance and inner membrane-associated replication of plasmid RK2 were enhanced in a Dp knockout strain and inhibited in strains containing extra copies of the Dp gene or in membrane extracts to which a tagged form of Dp was added. Recently, the Dp was independently shown to help prevent overinitiation in E. coli and was termed Hda (S. Kato and T. Katayama, EMBO J. 20:4253-4262, 2001).