Exploring the Diagnostic Dilemma of Indeterminate Pulmonary Nodules in Patients with Primary Sarcoma of Bone.

Introduction: Bone sarcomas are known to have a predilection for pulmonary metastasis. Surveillance protocols are thus focused on periodic chest imaging, typically with CT scan. Pulmonary nodules can be easily identified with this modality, but smaller nodules are not readily biopsied and may not represent metastatic disease. These are called indeterminate. The natural history of indeterminate nodules in a bone sarcoma population and factors associated with progression to true metastatic disease are not clearly defined. Methods: All bone sarcoma patients treated at a single institution from 2010 to 2020 were eligible for inclusion. We treated 327 patients over this period; 119 were excluded for age less than 16 years, 31 were excluded for evident metastatic disease at presentation, and 60 were excluded for incomplete clinical follow-up or CT chest imaging either at staging or in surveillance. We assessed chest CT images for presence of pulmonary nodules and selected variables both at the staging and on surveillance images. Nodules were considered metastatic if proven histologically with a biopsy or by clinical interpretation by the multidisciplinary sarcoma team. Clinical and imaging factors were assessed for the association of indeterminate nodule progression to true metastatic disease. Results: Seventy three of the 117 patients had indeterminate nodules on their staging CT scan; 41.1% of those patients progressed to metastatic disease compared to 43.2% of the patients that did not have indeterminate nodules on staging CT. Fifty eight of the 117 patients developed indeterminate nodules on surveillance chest CT, and 55.2% of those patients progressed to metastatic disease. There were no clinical or imaging factors that predicted the development of metastatic disease in the group that had indeterminate nodules at presentation; however, the number and size of nodules did correlate with progression to metastasis in those that developed indeterminate nodules on surveillance. Conclusion: Indeterminate pulmonary nodules are common on staging CT scans in patients with a bone sarcoma. The presence or absence of these indeterminate nodules was not predictive of progression to true metastatic disease in this cohort. However, the development of indeterminate nodules on surveillance imaging was associated with progression to metastatic disease with the size and number of nodules being important factors.

ASPSCR1-TFE3 reprograms transcription by organizing enhancer loops around hexameric VCP/p97.

The t(X,17) chromosomal translocation, generating the ASPSCR1::TFE3 fusion oncoprotein, is the singular genetic driver of alveolar soft part sarcoma (ASPS) and some Xp11-rearranged renal cell carcinomas (RCCs), frustrating efforts to identify therapeutic targets for these rare cancers. Here, proteomic analysis identifies VCP/p97, an AAA+ ATPase with known segregase function, as strongly enriched in co-immunoprecipitated nuclear complexes with ASPSCR1::TFE3. We demonstrate that VCP is a likely obligate co-factor of ASPSCR1::TFE3, one of the only such fusion oncoprotein co-factors identified in cancer biology. Specifically, VCP co-distributes with ASPSCR1::TFE3 across chromatin in association with enhancers genome-wide. VCP presence, its hexameric assembly, and its enzymatic function orchestrate the oncogenic transcriptional signature of ASPSCR1::TFE3, by facilitating assembly of higher-order chromatin conformation structures demonstrated by HiChIP. Finally, ASPSCR1::TFE3 and VCP demonstrate co-dependence for cancer cell proliferation and tumorigenesis in vitro and in ASPS and RCC mouse models, underscoring VCP's potential as a novel therapeutic target.

ASPSCR1-TFE3 reprograms transcription by organizing enhancer loops around hexameric VCP/p97.

The t(X,17) chromosomal translocation, generating the ASPSCR1-TFE3 fusion oncoprotein, is the singular genetic driver of alveolar soft part sarcoma (ASPS) and some Xp11-rearranged renal cell carcinomas (RCC), frustrating efforts to identify therapeutic targets for these rare cancers. Proteomic analysis showed that VCP/p97, an AAA+ ATPase with known segregase function, was strongly enriched in co-immunoprecipitated nuclear complexes with ASPSCR1-TFE3. We demonstrate that VCP is a likely obligate co-factor of ASPSCR1-TFE3, one of the only such fusion oncoprotein co-factors identified in cancer biology. Specifically, VCP co-distributed with ASPSCR1-TFE3 across chromatin in association with enhancers genome-wide. VCP presence, its hexameric assembly, and its enzymatic function orchestrated the oncogenic transcriptional signature of ASPSCR1-TFE3, by facilitating assembly of higher-order chromatin conformation structures as demonstrated by HiChIP. Finally, ASPSCR1-TFE3 and VCP demonstrated co-dependence for cancer cell proliferation and tumorigenesis in vitro and in ASPS and RCC mouse models, underscoring VCP's potential as a novel therapeutic target.

Thermal necrosis in orthopedic bone tumors: experimental research.

Introduction: The extent of surgical resection in orthopedic oncology differs according to tumor biology. While malignant bone tumors are operatively managed with wide resection, benign bone tumors and metastatic carcinomas are often treated through intralesional excision and adjuvant modalities, including the elimination of residual neoplastic cells through thermal necrosis. This study investigates in vitro temperature thresholds for thermal necrosis in common orthopedic bone tumors. Methodology: Eleven cell lines, including metastatic carcinomas to bone (A549, A498, FU-UR-1, PC3, MDA-MB-231, TT, MCF7, and K1), giant cell tumor of bone, osteosarcoma (HG-63), and control non-neoplastic cells (HEK293) were cultured. Cells were exposed to thermal stress at varying times and temperatures and evaluated for survival and viability with crystal violet and MTT assays. Results: Both the MTT and crystal violet assay demonstrated statistically superior rates of viability and survival for A549 (lung carcinoma), FU-UR-1 (renal carcinoma), K1 (thyroid carcinoma), and MG-63 (osteosarcoma) cell lines compared to control (HEK293 cells) at 60°C. Additionally, the MTT assay demonstrated superior viability for PC3 (prostate carcinoma), MCF7 (breast carcinoma), and A498 (renal carcinoma) compared to control. All cell lines demonstrated significantly decreased survival and viability in temperatures more than 90°C. Conclusion: This study demonstrated in vitro thresholds for thermal necrosis for cell lines of common orthopedic tumors of bone. The A549 (lung carcinoma), K1 (thyroid carcinoma), and FU-UR-1 (renal carcinoma) cell lines demonstrated greater resistance to heat stress compared to non-neoplastic control cells. Temperatures in excess of 90°C are necessary to reliably reduce cell survival and viability to less than 10%.

Thermal properties of polymethyl methacrylate vary depending on brand and type.

Polymethyl methacrylate (PMMA) is commonly used in orthopedic surgery and has several applications, most often for fixation of arthroplasty components. While its overall safety and tolerance are well described, less is known regarding the thermal properties of PMMA as it sets from a liquid to solid state, as well as the potential for osseous thermal necrosis. This study addresses potential variations in the setting time and maximum temperature of PMMA formulations in common use and explores the potential clinical implications of this variability. Seven commercially available formulations of PMMA that varied by brand and/or viscosity were obtained and prepared according to manufacturer's instructions. Peak temperature and duration were measured in controlled settings for each type and compared to previously described thresholds for thermal bone necrosis. Depuy SmartSet (HV), Zimmer Palacos R (HV), and Zimmer Palacos (LV) exceeded the 56°C threshold reported to potentially induce immediate osseous thermal necrosis. Additionally, Biomet Cobalt (MV) and Stryker Simplex P (MV) had lower peak temperatures but exceeded thermal necrosis thresholds due to curing duration. The lowest peak temperature was observed for Smith & Nephew Versabond (MV), which was significantly lower than all types except Depuy SmartSet (MV). Setting time was not significantly different among groups. There are significant differences in the thermal properties of PMMA formulations in current use. Selection of specific PMMA formulations represents an additional route of procedural optimization depending on the needs of the treating surgeon.

Ewing sarcoma of the pelvis: Clinical features and overall survival.

INTRODUCTION: Primary Ewing Sarcoma of Bone is a malignancy whose treatment requires both systemic chemotherapy and local control through surgical resection and/or radiation. Ewing Sarcoma of the pelvis has been noted to confer a worse prognosis relative to other anatomic sites of Ewing Sarcoma. This study explores the presenting features, treatment modalities for local control, and overall survival of primary Ewing sarcoma of the pelvis in comparison to other commonly affected anatomic sites. METHODS: The National Cancer Institute Surveillance, Epidemiology, and End-Results (SEER) database was used to identify cases of pelvic Ewing sarcoma diagnosed between years 2004 and 2015. Demographic variables including sex, race, and age at diagnosis were described for each case, as well as therapeutic modalities including surgery and radiation. Bone-specific Collaborative Staging variables, including tumor size, tumor extension, and metastasis at diagnosis, were described for the same cohort. Univariate and multivariate assessments were performed for statistical comparison between presenting factors, treatment modalities, and between anatomic locations of presentation. RESULTS: Within the database, 296 patients with Ewing sarcoma of the pelvic bones were available for review, which represented 25.7% of the 1152 cases surveyed across all anatomic sites. In the subset of patients with Ewing Sarcoma of the pelvis, 63.5% were male; the median age of diagnosis was 17 years; extra-compartmental tumor extension was noted in 82.1%; average tumor size was 9.7 cm; and metastasis at diagnosis was noted in 46.1% of the cohort. Only 28.6% of the pelvis sarcoma patients received surgical resection as part or all of their local control treatment, while 67.6% received some form of radiation therapy. When compared to the presenting features of Ewing Sarcoma from other anatomic sites, patients with pelvic tumors had larger tumors at time of diagnosis, higher rates of metastatic disease, and were less likely to undergo surgical intervention. The 2-, 5-, and 10-year overall survival rates for the patients presenting with Ewing Sarcoma of the pelvis was 70.3%, 49.7%, and 41.9%, respectively, which were significantly lower across all time-points than any other anatomic site. DISCUSSION AND CONCLUSION: Ewing Sarcoma of the pelvis is an aggressive malignancy that presents with relatively large tumors and a high rate of metastatic dissemination. Surgical intervention is less frequent when Ewing Sarcoma presents in the pelvis than when it presents in other anatomic locations. These factors may contribute to the worse overall survival of Ewing Sarcoma when compared to the same diagnosis originating in other anatomic sites. Prospective, randomized study is required to determine the true causal effects of these factors on survival.

Radiation Therapy in Conjunction With Surgical Stabilization of Impending or Pathologic Fractures Secondary to Metastasis: Is There a Difference Between Single and Multifraction Regimens?

PURPOSE: Patients who undergo surgical stabilization for impending or pathologic fractures secondary to metastasis are often treated with radiation therapy to the involved site. We sought to retrospectively analyze outcomes from single versus multifraction regimens of radiation therapy in this setting. METHODS AND MATERIALS: From our institutional radiation database, we identified 87 patients between 2004 and 2016 who had an impending or pathologic fracture from metastatic disease and who underwent surgical fixation in conjunction with either neoadjuvant (within 5 weeks before surgery) or adjuvant (within 10 weeks after surgery) radiation therapy, representing 99 total treatment sites. Patients were included on the basis of intention to treat with bimodality therapy. Baseline patient characteristics were compared using 2-sided t tests and Fisher's exact tests. Cumulative incidence of local failure, reirradiation, and reoperation were calculated using the Fine-Gray method for competing risks. Freedom from complication was calculated using the Kaplan-Meier method. RESULTS: Baseline characteristics between the single (n = 52) and multifraction (n = 47) cohorts were similar with the exception of higher rates of synchronous bony metastasis (83% vs 60%, P = .01) and female patients (71% vs 43%, P = .004) in the single fraction cohort. There was no significant difference in overall survival between treatment groups. After a median follow-up of 13 months, there was no significant difference in the single and multifraction cohorts, respectively, in the 1-year cumulative incidence rates of local failure (4% vs 7%, P = .58), reirradiation (5% vs 4%, P = .95), reoperation (4% vs 0%, P = .30), or 1-year freedom from complication (90% vs 95%, P = .40). CONCLUSIONS: This is the first study comparing outcomes between single and multifraction radiation therapy in conjunction with surgical stabilization of an impending or pathologic fracture. We found no difference in outcomes between single and multifraction regimens in this setting. Given these findings, single fraction perioperative radiation therapy may be a viable treatment option in appropriately selected patients pending prospective validation of these findings.

Presenting features and overall survival of chondrosarcoma of the pelvis.

INTRODUCTION: Chondrosarcoma is the second most common sarcoma of bone. This sarcoma is generally unresponsive to chemotherapy and radiation and is primarily managed through surgical excision. Pelvic chondrosarcoma presents a distinct therapeutic challenge due the complexity of resection, frequent recurrence and metastasis, and high post-operative morbidity. METHODS: The SEER database was queried for pelvic chondrosarcoma diagnosed between 2004 and 2015. Cases were described by age, sex, tumor size, extension, grade, metastasis, and therapeutic intervention. These same variables were assessed for the upper extremities, lower extremities, skull and facial bones, thoracic bones, and vertebral column. RESULTS: In total, 472 cases of pelvic chondrosarcoma were identified, representing 18.4% out of 2571 cases of chondrosarcoma distributed throughout the skeletal system. Among pelvic cases, 288 were male and 184 were female, with a median age of diagnosis of 54. Median tumor size was 96 mm, 64.9% of tumors were considered extracompartmental, and 11.3% of tumors were metastatic at time of diagnosis. The 2, 5, and 10-year survival rates for all cases of primary chondrosarcoma of the pelvis are 76.7%, 61.8%, and 52.2%, respectively. Survival was worse for patients with metastasis, male sex, age >60, tumor size >8 cm, dedifferentiated histology, and no surgical resection. On multivariate assessment high grade and metastasis most significantly predicted worse overall survival. CONCLUSION: Pelvic chondrosarcoma commonly presents with high-risk features including larger tumor size, extracompartmental extension, and metastatic disease at diagnosis, predicting worse overall survival compared to non-pelvic tumors, and were the least amenable to surgical resection.

What Are the Long-term Surgical Outcomes of Compressive Endoprosthetic Osseointegration of the Femur with a Minimum 10-year Follow-up Period?

BACKGROUND: Endoprosthetic reconstruction after oncologic resection of bone tumors requires stable fixation between the prosthesis and residual host bone. Compressive osseointegration has been developed as an alternative to traditional stemmed implants to address the challenges and complications of achieving this fixation. Sufficient time has now passed from the advent of compressive implants to allow for an assessment of the intermediate-term and long-term results of this form of fixation. QUESTIONS/PURPOSES: At a minimum follow-up of 10 years after implantation of a compressive osseointegration device for oncologic reconstruction: (1) What is the risk of periprosthetic fracture, aseptic loosening, or implant breakage resulting in revision surgery for endoprosthesis removal? (2) What is the long-term cortical response at the host-endoprosthesis interface as visualized on plain radiographs? METHODS: A single-center, retrospective study was performed between 2002 and 2010, in which 110 patients with primary bone sarcoma of the proximal or distal femur were considered for oncologic resection and reconstruction. Patients were considered for a compressive osseointegration endoprosthesis if they were 50 years of age or younger, had not previously received femoral radiation, had no metabolic disease impairing bone healing, were not diagnosed with metastatic disease, and had life expectancy greater than six months. Of the 110 patients, 25 were treated with a compressive osseointegration implant of the proximal or distal femur, and 85 patients were treated with conventional stemmed implants or amputation because of older age, advanced disease, metabolic comorbidities, inability to tolerate a nonweightbearing postoperative period, or in the case of rotationplasty, patient preference. All patients who received this device during the period of study were considered eligible for inclusion in this review. The median (range) age was 18 years (7 to 50), and 13 of 25 patients were men. Five patients died of disease before the minimum follow-up duration of 10 years; two underwent amputation due to local recurrence and three died with the implant in situ, leaving 20 patients for complete analysis. Median follow-up was 144 months, and all 20 surviving patients had a minimum follow-up of 10 years (121 to 230 months). The primary endpoint was reoperation and implant removal for periprosthetic fracture, aseptic loosening, or mechanical breakage of any component of the compressive device in the endoprosthesis. In final analysis, death was considered a competing event to revision surgery, and cumulative incidence was reported after competing-event analysis. A secondary aim was radiographic evaluation of the host-implant interface to assess the long-term cortical response to compressive osseointegration. RESULTS: Spindle fracture or loosening was noted in three patients, and the remaining 17 patients maintained the compression device until the final follow-up. The risk of reoperation for aseptic loosening, periprosthetic fracture, or mechanical breakage of the implant using a competing risks estimator was 12% at 10 years (95% CI 0% to 26%). These complications occurred within 29 months of the index surgery; no patients had implant loosening or mechanical breakdown after this initial period. On radiographic assessment, 14 patients demonstrated cortical hypertrophy of the bone-implant interface, six patients had maintenance of the native cortical contour, and no patients had cortical atrophy or narrowing at the implant interface.Conclusion Long-term follow-up in patients with compressive osseointegrative endoprosthetic devices demonstrated no late revisions because of periprosthetic fracture, aseptic loosening, or implant breakage in this cohort with a minimum 10-year follow-up. There was no evidence of late-onset cortical atrophy or stress shielding at the host-implant interface. This study supports the long-term stability of the interface between host bone and the endoprosthesis in compressive osseointegration devices. LEVEL OF EVIDENCE: Level IV, therapeutic study.

Osteosarcoma of the Pelvis: Clinical Presentation and Overall Survival.

INTRODUCTION: Osteosarcoma is the most common sarcoma of bone. Pelvic osteosarcoma presents a significant therapeutic challenge due to potential late symptom onset, metastatic dissemination at diagnosis, and inherent difficulties of wide surgical resection secondary to the complex and critical anatomy of the pelvis. The rates of survival are well reported for osteosarcoma of the appendicular skeleton, but specific details regarding presentation and survival are less known for osteosarcoma of the pelvis. METHODS: The Surveillance, Epidemiology, and End Results (SEER) program was queried for primary osteosarcoma of the bony pelvis from 2004 to 2015. Cases with Collaborative Staging variables (available after 2004) were analyzed by grade, histologic subtype, surgical intervention, tumor size, tumor extension, and presence of metastasis at diagnosis. The 2-, 5-, and 10-year survival rates were assessed with respect to these variables. The SEER database was then queried for age, tumor size, surgical intervention, metastasis at time of presentation, and survivorship data for patients with primary osteosarcoma of the upper extremity, lower extremity, vertebrae, thorax, and face/skull, and rates for all anatomic locations were then compared to patients with primary pelvic osteosarcoma. RESULTS: A total of 292 cases of pelvic osteosarcoma were identified from 2004 to 2015 within the database, representing 9.8% of cases among all surveyed primary sites. The most common histologic subtype was osteoblastic osteosarcoma (69.9%), followed by chondroblastic osteosarcoma (22.3%). The majority of cases were high-grade tumors (94.3%), of size >8 cm (72.0%), and with extension beyond the originating bone (74.0%). For the entire pelvic osteosarcoma group, the 2-, 5-, 10-year survival rates were 45.6%, 26.5%, and 21.4%, respectively, which were the poorest among surveyed anatomic sites. The 5-year overall survival was an abysmal 5.3% for patients with metastatic disease at diagnosis, and 37.0% for non-metastatic pelvic osteosarcoma treated with surgery and chemotherapy. When compared to other locations, pelvic osteosarcoma had higher rates of metastatic disease at presentation (33.5%), larger median tumor size (11.0 cm), and older median age at diagnosis (47.5 years). While over 85% of patients with tumors at the extremities received surgery, only 47.4% of pelvic osteosarcomas in this cohort received surgical resection-likely influenced by larger tumor size, sacral involvement, frequency of metastasis, older age, or delayed referral to a sarcoma center. CONCLUSION: This study clarifies presenting features and clinical outcomes of pelvic osteosarcomas, which often present with large, high-grade tumors with extracompartmental extension, high likelihood of metastatic disease at diagnosis, and a potential limited ability to be addressed surgically. The survival rates of primary osteosarcoma of the pelvis are poor and are lower than osteosarcomas from other anatomic locations. While acknowledging the influence of metastasis, tumor characteristics, and advanced age on the decision to undergo surgical excision of a pelvic osteosarcoma, the rates of surgical resection are low and highlight the importance of understanding appropriate conditions for oncologic resection of pelvic sarcomas.

Metastasis of Osteosarcoma to the Abdomen: A Report of Two Cases and a Review of the Literature.

Two cases of primary distal femur osteosarcoma with subsequent metastasis to the abdomen are presented. In both cases, the development of abdominal metastasis was quickly followed by patient decline and death. A review of the literature was performed, assessing the presentation and survival of patients with osteosarcoma metastasized to the abdomen. As illustrated by the current cases and the literature review, abdominal metastasis in osteosarcoma is often a late manifestation and terminal prognostic indicator. Nonetheless, early detection and prompt intervention of this less common site of disease metastasis may improve patient care and palliative therapy.

Is osseous reattachment of the greater trochanter necessary compared to soft-tissue-only abductor repair in proximal femoral megaprosthesis reconstruction?

BACKGROUND: One of the challenges to surgical reconstruction following oncologic proximal femur resection is reliable re-establishment of the abductor mechanism. Surgical and functional outcomes following re-approximation of the abductor mechanism to a metallic endoprosthetic after tumor resection of the proximal femur have not been well established in the literature. METHODS: A retrospective review was performed, inclusive of patients who received a proximal femur replacement with a metallic endoprosthesis following tumor resection. Patients were divided into two groups: (1) those that received an abductor repair involving a trochanteric osteotomy and osseous fixation of the greater trochanter/abductor mechanism to the endoprosthesis, and (2) those that did not have a trochanteric osteotomy and therefore had an abductor repair consisting of only soft tissue reattachment to the endoprosthesis. The two groups were assessed for demographic characteristics, diagnosis, surgical outcomes including rates of complication and failure, radiographic evidence of trochanteric failure, and functional outcomes. Descriptive statistics, comparative statistics, and logistic regression analyses were performed to discern differences between the two study groups. RESULTS: Fifty-three patients were included in the analysis, 29 had abductor reconstructions involving reattachment of the greater trochanter to the metallic endoprosthesis and 24 had soft tissue reconstruction of the abductor mechanism without bony fixation. There were no differences between the two groups for demographic data, cancer diagnosis, follow up, or survivorship. Radiographic evidence of trochanteric dissociation from the endoprosthesis was observed in 45% of osteotomy cases. Only 10% of patients in the trochanter osteotomy group and 38% of the soft tissue only group were able to resume a normal, non-Trendelenburg gait at final postoperative visit (p = .024). Need for an assistive ambulatory device was seen in 83% and 67% of the osteotomy and soft-tissue-only patients, respectively (p = .21). CONCLUSION: Re-establishing the abductor mechanism following proximal femur oncologic resection remains a challenge to orthopedic oncologists. Even when possible, salvage of the greater trochanter for reattachment to the endoprosthesis did not lead to improved function in this series, when compared to a similar cohort that received a soft-tissue-only abductor repair. Abductor mechanism reconstruction with a greater trochanteric osteotomy and subsequent fixation to the proximal femur endoprosthesis had a high rate of radiographic failure. Additionally, reattachment of the greater trochanter to the proximal femur endoprosthesis demonstrated no improvement in Trendelenburg gait or reliance on an assistive ambulatory device when compared to a soft-tissue-only abductor repair.

Ischial osteoid osteoma: A cause of persistent hip pain in an adolescent patient with bilateral femoroacetabular impingement.

A 15-year-old boy presented with left-sided hip pain and imaging consistent with the diagnosis of femoroacetabular impingement. Following hip arthroscopy, which included an osteochondroplasty, labral repair, and capsular repair, the patient's anterior hip pain improved. However, his deep aching hip pain persisted until an ischial osteoid osteoma was identified and treated with radiofrequency ablation. At 3 years follow-up, the patient reports high satisfaction and minimal pain. We present this case to illustrate the importance of considering all potential causes of persistent hip pain following hip arthroscopy, including benign bone tumors which may be difficult to visualize on plain radiographs.

Nonmechanical Revision Indications Portend Repeat Limb-Salvage Failure Following Total Femoral Replacement.

BACKGROUND: There is scant evidence to guide decision-making for patients considering total femoral replacement (TFR). We aimed to identify the indication, patient, disease, and surgical technique-related factors associated with failure. We hypothesized that failure occurs more frequently in the setting of revision surgical procedures, with infection as the predominant failure mode. METHODS: We performed a retrospective cohort study of patients receiving total femoral endoprostheses for oncological and revision arthroplasty indications; 166 patients met these criteria. Our primary independent variable of interest was TFR for a revision indication (arthroplasty or limb salvage); the primary outcome was failure. Analyses were performed for patient variables (age, sex, diagnosis group, indication), implant variables (model, decade, length, materials), and treatment variables. We analyzed TFR failures with respect to patient factors, operative technique, and time to failure. We conducted bivariate logistic regressions predicting failure and used a multivariate model containing variables showing bivariate associations with failure. RESULTS: Forty-four patients (27%) had treatment failure. Failure occurred in 24 (23%) of 105 primary TFRs and in 20 (33%) of 61 revision TFRs; the difference was not significant (p = 0.134) in bivariate analysis but was significant (p = 0.044) in multivariate analysis. The mean age at the time of TFR was 37 years in the primary group and 51 years in the revision group (p = 0.0006). Of the patients who had mechanical failure, none had reoccurrence of their original failure mode, whereas all 8 patients from the nonmechanical cohort had reoccurrence of the original failure mode; this difference was significant (p = 0.0001). CONCLUSIONS: TFR has a high failure rate and a propensity for deep infection, especially in the setting of revision indications and prior infection. All failed TFRs performed for revision indications for infection or local recurrence failed by reoccurrence of the original failure mode and resulted in amputation. LEVEL OF EVIDENCE: Therapeutic Level IV. See Instructions for Authors for a complete description of levels of evidence.

Free tibia and fibula-fillet-of-leg flap for pelvic ring reconstruction: A case report.

Pelvic sarcoma resections present large and complex defects, which are a challenge to reconstruct. At times, these cancers are treated with external hemipelvectomy, and both the soft tissue and bony framework of the pelvic ring must be addressed. The purpose of this case report is to describe the use of a free tibia and fibula-fillet-of-leg flap for pelvic ring reconstruction, performed to enhance the quality of life of a patient following hemipelvectomy. A 50-year-old female with advanced stage undifferentiated pleomorphic sarcoma of the left thigh and pelvis underwent free vascularized tibia and fibula-fillet-of-leg flap, including 21 cm of bone length and 21 cm long and full circumferential soft tissues of the leg, accompanying the bone, for the reconstruction of the bony pelvis and soft tissue. Postoperatively, the patient had no surgical complications, was followed for 6 months and went on to have bony healing, and was able to sit prior to disease progression and eventual death from metastatic disease. In the reported case, we have shown that composite tibia-fibula free flap with lower leg soft tissues may be a viable option for the reconstruction of massive external hemipelvectomy defects.

Comparison of 3 Methods for Maintaining Inter-Fragmentary Compression After Fracture Reduction and Fixation.

OBJECTIVES: It is recommended that the intra-articular component of a supracondylar distal femoral fracture be stabilized by a lag screw to create interfragmental compression. Generally, it is thought that lag screw fixation should precede any positional screw or locking screw application. This study compared 3 methods of maintaining interfragmentary compression after fracture reduction with a reduction clamp. METHODS: Intra-articular vertical split fractures were created in synthetic femora. A force transducer was interposed between the medial and lateral condyles and 20 lbs of compression was applied to the fracture with a reduction clamp. 3.5-mm cortical lag screws (group 1), 3.5-mm cortical position screws (group 2), and 5.4-mm distal locking screws through a distal femur locking plate (group 3) were placed across the fracture (n = 4/group). After screw placement, the clamp was removed and the amount of residual interfragmentary compression was recorded. After 2 minutes, a final steady-state force was measured and compared across groups. RESULTS: Locking screws placed through the plate (group 3) maintained 27% of the initial force applied by the clamp (P = 0.043), whereas positional screws (group 2) maintained 90% of the initial force applied by the clamp (P = 0.431). The steady-state compression force measured with lag screws (group 1) increased by 240% (P = 0.030) relative to the initial clamp force. The steady-state force in the lag screw group was significantly greater than groups 1 and 2 (P = 0.012). CONCLUSIONS: When reducing intra-articular fractures and applying interfragmentary compression with reduction clamps, additional lag screws increase the amount of compression across the fracture interface. Compressing a fracture with reduction clamps and relying on locking screws to maintain the compression result in a loss of interfragmentary compression and should be avoided. This study lends biomechanical support that lag screws placed outside of the plate before locking screws for fracture fixation help maintain optimal interfragmentary compression.

Surgical and Functional Outcomes After Limb-Preservation Surgery for Tumor in Pediatric Patients: A Systematic Review.

BACKGROUND: Limb-salvage surgery and segmental reconstruction for the treatment of lower extremity osseous tumors in the pediatric population have been described in the literature, but there is little consensus regarding the optimal surgical treatment for this patient population. METHODS: A systematic review of the literature was performed to identify studies focusing on limb-salvage procedures in pediatric patients who were managed with one of three reconstructions with use of a metallic endoprosthesis, allograft, or allograft-prosthesis composite. Data were segregated according to the excised and reconstructed anatomical location (proximal part of the femur, total femur, distal part of the femur, proximal part of the tibia) and were collated to assess modes of failure and functional outcomes of each reconstruction type for each anatomic location. RESULTS: Sixty articles met the inclusion criteria; all were Level-IV evidence, primarily consisting of small, retrospective case series. Infection was a primary mode of failure across all reconstruction types and locations, whereas allograft reconstructions were susceptible to structural failure as well. The rate of failure in the pediatric population correlated well with previously published results for adults. The incidence of subsequent amputation was lower in the pediatric population (5.2%) than has been reported in adults (9.5%) (p = 0.013). Meaningful growth of expandable metallic endoprostheses was reported in the literature, with an overall rate of leg-length discrepancy of 13.4% being noted at the time of the latest follow-up. The Musculoskeletal Tumor Society (MSTS) questionnaire was the most consistently used outcome measure in the literature, with average scores ranging from 71.0% to 86.8%, depending on reconstruction type and anatomic location. CONCLUSIONS: The current state of the literature detailing the surgical and functional outcomes of segmental reconstruction for the treatment of pediatric bone tumors is limited to Level-IV evidence and is complicated by under-segregation of the data by age and anatomical location of the reconstruction. Despite these limitations, pediatric limb-salvage surgery demonstrates satisfactory initial surgical and functional outcomes. LEVEL OF EVIDENCE: Therapeutic Level IV. See Instructions for Authors for a complete description of levels of evidence.

Reconstruction After Tumor Resection in the Growing Child.

Limb preservation surgery has gained acceptance as a viable alternative to amputation for the treatment of extremity bone tumors in the growing child. There are several options for reconstructing the potential loss of a physis and the defect created by tumor excision. Metallic endoprosthesis, massive allograft, and allograft-prosthesis composites have been described in the skeletally immature population. With the development of expandable prostheses, even those far from skeletal maturity may be candidates for limb salvage. However, improvements in the literature are needed, including reporting surgical and functional outcomes in a rigorous manner, specific to age, anatomic location, and reconstruction.

Expandable Total Humeral Replacement in a Child with Osteosarcoma.

Case. A right-handed 8-year-old female patient presented with a conventional, high-grade osteosarcoma involving her right humerus; through-shoulder amputation was recommended. After consultation, total humerus resection with expandable, total humeral endoprosthesis reconstruction was performed with a sleeve to encourage soft-tissue ingrowth. At three-year follow-up she has received one lengthening procedure and her functional scores are excellent. Conclusion. Total humeral resection and replacement in the pediatric population are rare and although early reports of expandable total humeral endoprosthesis outcomes demonstrate high failure rates, this patient's success indicates that expandable total humeral replacement is a viable option.

Advances in segmental endoprosthetic reconstruction for extremity tumors: a review of contemporary designs and techniques.

BACKGROUND: Improved understanding and advances in treatment regimens have led to increased longevity among patients diagnosed with extremity soft tissue sarcomas. Limb salvage techniques and implants have improved and continue to evolve to accommodate the increasing demands and survival of these patients. METHODS: The current report is a review of the literature for recent advancements in techniques, implant design, and outcomes in the field of limb salvage therapy using segmental megaprostheses for the treatment of extremity sarcomas. We report on our experience in this field utilizing a classification system of failure mechanisms to outline to discuss current controversies in management. RESULTS: Five mechanisms of failure have been identified: soft-tissue failure, aseptic loosening, structural failure, infection, and tumor progression. Infection was the most common mode of failure in our series, accounting for 34% of cases. Soft-tissue failure occurred most commonly in the joints that depend heavily on periarticular muscles and ligaments for stability due to their high degree of functional range of motion. We observed a 28% soft-tissue failure rate about the shoulder and hip, aseptic loosening accounted for 19% of implant failures, and structural failure was seen in 17% of cases. Seventeen percent of cases failed due to tumor progression, an etiology that is defined by biological factors, surgical technique, and adjuvant therapies. CONCLUSIONS: Surgical techniques and megaprosthesis designs are constantly changing in order to meet the challenge of increasing functional demands and longevity in this unique patient population. A classification system defined by treatment failure etiologies provides the framework for discussion of current controversies in limb salvage therapy as well as a guide for advancement and potential solutions in this challenging arena.