Rationale and design of the HIP fracture Accelerated surgical TreaTment And Care tracK (HIP ATTACK) Trial: a protocol for an international randomised controlled trial evaluating early surgery for hip fracture patients.

INTRODUCTION: Annually, millions of adults suffer hip fractures. The mortality rate post a hip fracture is 7%-10% at 30 days and 10%-20% at 90 days. Observational data suggest that early surgery can improve these outcomes in hip fracture patients. We designed a clinical trial-HIP fracture Accelerated surgical TreaTment And Care tracK (HIP ATTACK) to determine the effect of accelerated surgery compared with standard care on the 90-day risk of all-cause mortality and major perioperative complications. METHODS AND ANALYSIS: HIP ATTACK is a multicentre, international, parallel group randomised controlled trial (RCT) that will include patients ≥45 years of age and diagnosed with a hip fracture from a low-energy mechanism requiring surgery. Patients are randomised to accelerated medical assessment and surgical repair (goal within 6 h) or standard care. The co-primary outcomes are (1) all-cause mortality and (2) a composite of major perioperative complications (ie, mortality and non-fatal myocardial infarction, pulmonary embolism, pneumonia, sepsis, stroke, and life-threatening and major bleeding) at 90 days after randomisation. All patients will be followed up for a period of 1 year. We will enrol 3000 patients. ETHICS AND DISSEMINATION: All centres had ethics approval before randomising patients. Written informed consent is required for all patients before randomisation. HIP ATTACK is the first large international trial designed to examine whether accelerated surgery can improve outcomes in patients with a hip fracture. The dissemination plan includes publishing the results in a policy-influencing journal, conference presentations, engagement of influential medical organisations, and providing public awareness through multimedia resources. TRIAL REGISTRATION NUMBER: NCT02027896; Pre-results.

An evaluation of TAZ and YAP crosstalk with TGFß signalling in canine osteosarcoma suggests involvement of hippo signalling in disease progression.

BACKGROUND: Osteosarcoma (OSA) is the most common bone cancer in canines. Both transforming growth factor beta (TGFß) and Hippo pathway mediators have important roles in bone development, stemness, and cancer progression. The role of Hippo signalling effectors TAZ and YAP has never been addressed in canine OSA. Further, the cooperative role of TGFß and Hippo signalling has yet to be explored in osteosarcoma. To address these gaps, this study investigated the prognostic value of TAZ and YAP alone and in combination with pSmad2 (a marker of active TGFß signalling), as well as the involvement of a TGFß-Hippo signalling crosstalk in tumourigenic properties of OSA cells in vitro. An in-house trial tissue microarray (TMA) which contained 16 canine appendicular OSA cases undergoing standard care and accompanying follow-up was used to explore the prognostic role of TAZ, YAP and pSmad2. Published datasets were used to test associations between TAZ and YAP mRNA levels, metastasis, and disease recurrence. Small interfering RNAs specific to TAZ and YAP were utilized in vitro alone or in combination with TGFß treatment to determine their role in OSA viability, proliferation and migration. RESULTS: Patients with low levels of both YAP and pSmad2 when evaluated in combination had a significantly longer time to metastasis (log-rank test, p = 0.0058) and a longer overall survival (log rank test, p = 0.0002). No similar associations were found for TAZ and YAP mRNA levels. In vitro, TAZ knockdown significantly decreased cell viability, proliferation, and migration in metastatic cell lines, while YAP knockdown significantly decreased viability in three cell lines, and migration in two cell lines, derived from either primary tumours or their metastases. The impact of TGFß signaling activation on these effects was cell line-dependent. CONCLUSIONS: YAP and pSmad2 have potential prognostic value in canine appendicular osteosarcoma. Inhibiting YAP and TAZ function could lead to a decrease in viability, proliferation, and migratory capacity of canine OSA cells. Assessment of YAP and pSmad2 in larger patient cohorts in future studies are needed to further elucidate the role of TGFß-Hippo signalling crosstalk in canine OSA progression.

Long-term Follow-up of the Use of a Synthetic Bone Graft Composite in the Surgical Management of Primary Bone Tumors.

The surgical management of benign and benign aggressive bone tumors typically involves intralesional curettage and reconstruction of the resulting defect with cement or bone graft material. At the authors' institution, an injectable synthetic calcium sulfate-calcium phosphate composite is now the standard graft material for these cases. This study reports the long-term follow-up, specifically the stability of bone regeneration, for the use of the synthetic graft material for oncologic reconstruction. Fourteen patients who underwent intralesional curettage of a primary bone tumor followed by cavitary reconstruction with synthetic graft material who had at least 4-year follow-up were identified from an institutional orthopedic oncology database. Clinical outcome data, focusing on long-term clinical and radiographic features of the reconstruction, were extracted from electronic and paper medical records. Seven females and 7 males were included (mean age at surgery, 28.1 years; range, 13-64 years). Follow-up ranged from 50 to 105 months (mean, 68 months). Most surgical reconstructions were done for the lower limb (n=11), and giant cell tumor of bone was the most common tumor treated. The mean amount of synthetic graft material used was 18.6 cm3. Complete radiographic resorption and new bone incorporation was observed within the first year, and bone remodeling was complete in all patients. Bone remodeling remained stable throughout the longer-term follow-up (ie, up to 9 years). The use of an injectable synthetic calcium sulfate-calcium phosphate composite is a viable option in the reconstruction of cavitary bone defects following intralesional curettage of primary benign bone tumors. This reconstruction technique was safe, with no long-term complications, and led to complete radiographic resorption and new bone incorporation with long-lasting stability. [Orthopedics. 2018; 41(6):e868-e875.].

Getting fit for hip and knee replacement: a protocol for the Fit-Joints pilot randomized controlled trial of a multi-modal intervention in frail patients with osteoarthritis.

BACKGROUND: Joint replacement provides significant improvements in pain, physical function, and quality of life in patients with osteoarthritis. With a growing body of evidence indicating that frailty can be treated, it is important to determine whether targeting frailty reduction in hip and knee replacement patients improves post-operative outcomes. OBJECTIVES: The primary objective is to examine the feasibility of a parallel group RCT comparing a preoperative multi-modal frailty intervention to usual care in pre-frail/frail older adults undergoing elective unilateral hip or knee replacements. The secondary objectives areTo explore potential efficacy of the multi-modal frailty intervention in improving frailty and mobility between baseline and 6 weeks post-surgery using Fried frailty phenotype and short performance physical battery (SPPB) respectively.To explore potential efficacy of the multi-modal frailty intervention on post-operative healthcare services use. METHODS/DESIGN: In a parallel group pilot RCT, participants will be recruited from the Regional Joint Assessment Program in Hamilton, Canada. Participants who are (1) ≥ 60 years old; (2) pre-frail (score of 1 or 2) or frail (score of 3-5; Fried frailty phenotype); (3) having elective unilateral hip or knee replacement; and (4) having surgery wait times between 3 and 10 months will be recruited and randomized to either the intervention or usual care group. The multi-modal frailty intervention components will include (1) tailored exercise program (center-based and/or home-based) with education and cognitive behavioral change strategies; (2) protein supplementation; (3) vitamin D supplementation; and (4) medication review. The main comparative analysis will take place at 6 weeks post-operative. The outcome assessors, data entry personnel, and data analysts are blinded to treatment allocation. Assessments: feasibility will be assessed by recruitment rate, retention rate, and data collection completion. Frailty and healthcare use and other clinical outcomes will be assessed. The study outcomes will be collected at the baseline, 1 week pre-operative, and 6 weeks and 6 months post-operative. DISCUSSION: This is the first study to examine the feasibility of multi-modal frailty intervention in pre-frail/frail older adults undergoing hip or knee replacement. This study will inform the planning and designing of multi-modal frailty interventional studies in hip and knee replacement patients. TRIAL REGISTRATION: ClinicalTrials.gov NCT02885337.

Chronology of the Radiographic Appearances of the Calcium Sulfate-Calcium Phosphate Synthetic Bone Graft Composite Following Resection of Bone Tumors: A Follow-up Study of Postoperative Appearances.

PURPOSE: The objective of the study was to characterize the radiographic appearance of graft resorption and new bone incorporation into a postresection defect of the calcium-sulfate calcium-phosphate synthetic bone graft composite following resection of benign bone tumours. METHODS: Twenty-five patients who underwent treatment with the CaSO4/CaPO4 synthetic graft following bone tumour resection were retrospectively identified from our oncology database. Postoperative radiographs were assessed for: 1) combined partial graft resorption and ingrowth at the graft site; 2) complete graft resorption with complete incorporation of new bone into the defect. After chronologically grouping radiographs, the volume of graft material used to fill bony defects, radiographic evidence of complications, and patterns of resorption were recorded. RESULTS: Partial resorption of graft material/partial ingrowth of new bone was seen in 21 patients at 2.5 months postoperatively. Complete resorption of graft with complete new bone incorporation at the graft site was seen in 94% of cases (15 of 16) by 10 months after surgery. Mean time to complete incorporation of new bone was 6.7 months. Time to resorption of the graft with new bone ingrowth was found to be related to the volume of graft used with smaller volumes showing earlier resorption. For all cases demonstrating resorption (21 of 21), the pattern observed was peripheral to central. Five patients developed complications, including tumour recurrence, cyst formation, and graft site infection. CONCLUSION: Our study suggests a characteristic time and volume related radiographic pattern of resorption and new bone ingrowth with the CaSO4/CaPO4 synthetic graft. Findings that deviate from this pattern may represent complication and warrant additional follow-up.

Atypical hip pain: coexistence of femoroacetabular impingement (FAI) and osteoid osteoma.

The objective of this article was to emphasize the importance of including less common causes of hip pain in a differential diagnosis, particularly when clinical and radiographic variables are atypical. This article presents the case of a 52-year-old patient with a history of progressive hip pain resulting from the coexistence of both a femoroacetabular impingement (FAI) and an intraarticular osteoid osteoma. The intraarticular osteoid osteoma was initially overlooked due to its unremarkable features on radiographic and resonance imaging. Consequently, the patient was surgically treated for FAI with only partial relief. An osteolytic nidus characteristic of osteoid osteoma was discovered only 1.5 years following surgery. The patient was subsequently treated for osteoid osteoma with anti-inflammatories, after which his pain began to resolve. The patient was completely pain free after 7 months. Level of evidence V.

Surgical management of bone metastases: quality of evidence and systematic review.

BACKGROUND: Surgical management of metastatic bone disease (MBD) is typically reserved for lesions with the highest risk of fracture. However, the high risk of perioperative complications associated with surgery may outweigh the benefits of improved pain and/or function. The goal of this study was to (1) assess the quality of current evidence in this domain; (2) confirm that surgical management of metastases to the long bones and pelvis/acetabulum provides pain relief and improved function; and (3) assess perioperative morbidity and mortality rates. METHODS: We conducted a systematic review of the literature for clinical studies that reported pain relief and function outcomes, as well as perioperative complications and mortality, in patients with MBD to the long bones and/or pelvis/acetabulum treated surgically. Multiple databases were searched up to January 2012. Pooled weighted proportions are reported. RESULTS: Forty-five studies were included in the final analysis, with 807 patients. All included studies were level IV with 'moderate' overall quality of evidence using the Methodological Index for Non-Randomized Studies scale. Pain relief following surgical management of metastases was 93, 91, and 93 % in the humerus, femur, and pelvis/acetabulum, respectively. Maintained or improved function after surgery was seen in 94, 89, and 94 % in the humerus, femur, and pelvis/acetabulum, respectively. Perioperative complications and mortality were 17 and 4 %, respectively. CONCLUSIONS: Despite the inherent limitations of the current evidence, a benefit for the surgical management of bone metastases to the long bones and pelvis/acetabulum is evident; however, there is still substantial risk of perioperative morbidity and mortality that should be considered.

A Systematic Review and Meta-Analysis of En-Bloc vs Intralesional Resection for Giant Cell Tumor of Bone of the Distal Radius.

INTRODUCTION: Surgical management of Giant Cell Tumor of Bone of the distal radius (GCTDR) remains controversial due to risk of local recurrence (LR) offset by functional limitations which result from en-bloc resection. This study aims to determine the oncologic and functional outcomes of wide excision (WE) vs intralesional curettage (IC) of GCTDR. METHODS: A complete search of the applicable literature was done. Included studies reported on patients from the same cohort who were surgically treated for GCTDR with WE or IC. Two reviewers independently assessed all papers. The primary outcome measure was LR. RESULTS: One-hundred-forty-one patients from six studies were included: 60 treated with WE, and 81 with IC. Five WE patients (8%) suffered LR whereas 25 IC patients (31%) did. The odds of LR were three times less in the WE group vs the IC group. MSTS1993 scores, where available, were on average 'good' with WE and 'excellent' with IC. CONCLUSIONS: Within statistical limitations the data support an attempt, where feasible, at wrist joint preservation and superior function with IC. Intralesional curettage is reasonable when the functional benefit outweighs the risk of recurrence as is the case in many cases of GCT of the distal radius.

Radiology-pathology conference: cutaneous angiosarcoma of the leg.

Cutaneous angiosarcoma is a rare aggressive vascular neoplasm with a poor prognosis, seen usually in the elderly population in a background of chronic lymphedema. We present a case of cutaneous angiosarcoma of the leg without any chronic lymphedema with clinicoradiological and histological correlation.

Use of a calcium sulfate-calcium phosphate synthetic bone graft composite in the surgical management of primary bone tumors.

Benign primary bone tumors are commonly treated with intralesional curettage with or without the use of surgical adjuvants. The reconstructive approach to the resulting contained bone defects is controversial, and clinical practice is varied. Synthetic bone substitutes may provide early mechanical support while minimizing the risks of disease transmission, nonunion, infection, and donor-site morbidity. Limited data exists regarding the use of calcium sulfate-calcium phosphate composite bone substitute for this purpose. The authors retrospectively reviewed the clinical outcomes of 24 patients with benign primary bone tumors who underwent intralesional curettage followed by reconstruction with a calcium sulfate-calcium phosphate composite bone substitute. Mean follow-up was 23 months. The most common diagnosis was giant cell tumor of bone. Six patients had upper-extremity tumors and 18 had lower-extremity tumors. Mean preoperative radiographic tumor volume was 41.0 cm(3). Mean volume of PRO-DENSE (Wright Medical Technology, Arlington, Tennessee) used in each patient was 15.6 cm(3). Mean time to full weight bearing for all patients was 7.3 weeks. Two patients sustained local tumor recurrences. No postoperative fractures occurred, and no complications occurred related to the use of the calcium sulfate-calcium phosphate composite. One case of deep infection occurred secondary to wound breakdown. The use of a calcium sulfate-calcium phosphate composite was associated with rapid biological integration and an early return to activities of daily living, with no composite-related complications. This technique is a viable option in the reconstruction of cavitary bone defects following intralesional curettage of primary benign bone tumors.

High infection rate outcomes in long-bone tumor surgery with endoprosthetic reconstruction in adults: a systematic review.

BACKGROUND: Limb salvage surgery (LSS) with endoprosthetic replacement is the most common method of reconstruction following bone tumor resection in the adult population. The risk of a postoperative infection developing is high when compared with conventional arthroplasty and there are no appropriate guidelines for antibiotic prophylaxis. QUESTIONS/PURPOSES: We sought to answer the following questions: (1) What is the overall risk of deep infection and the causative organism in lower-extremity long-bone tumor surgery with endoprosthetic reconstruction? (2) What antibiotic regimens are used with endoprosthetic reconstruction? (3) Is there a correlation between infection and either duration of postoperative antibiotics or sample size? METHODS: We conducted a systematic review of the literature for clinical studies that reported infection rates in adults with primary bony malignancies of the lower extremity treated with surgery and endoprosthetic reconstruction. The search included articles published in English between 1980 and July 2011. RESULTS: The systematic literature review yielded 48 studies reporting on a total of 4838 patients. The overall pooled weighted infection rate for lower-extremity LSS with endoprosthetic reconstruction was approximately 10% (95% CI, 8%-11%), with the most common causative organism reported to be Gram-positive bacteria in the majority of cases. The pooled weighted infection rate was 13% after short-term postoperative antibiotics and 8% after long-term postoperative antibiotics. There was no correlation between sample size and infection rate. CONCLUSIONS: Infection rates of 10% are high when compared with rates for conventional arthroplasty. Our results suggest that long-term antibiotic prophylaxis decreases the risk of deep infection. However, the data should be interpreted with caution owing to the retrospective nature of the studies.

Phase 2 study of preoperative image-guided intensity-modulated radiation therapy to reduce wound and combined modality morbidities in lower extremity soft tissue sarcoma.

BACKGROUND: This study sought to determine if preoperative image-guided intensity-modulated radiotherapy (IG-IMRT) can reduce morbidity, including wound complications, by minimizing dose to uninvolved tissues in adults with lower extremity soft tissue sarcoma. METHODS: The primary endpoint was the development of an acute wound complication (WC). IG-IMRT was used to conform volumes to avoid normal tissues (skin flaps for wound closure, bone, or other uninvolved soft tissues). From July 2005 to June 2009, 70 adults were enrolled; 59 were evaluable for the primary endpoint. Median tumor size was 9.5 cm; 55 tumors (93%) were high-grade and 58 (98%) were deep to fascia. RESULTS: Eighteen (30.5%) patients developed WCs. This was not statistically significantly different from the result of the National Cancer Institute of Canada SR2 trial (P = .2); however, primary closure technique was possible more often (55 of 59 patients [93.2%] versus 50 of 70 patients [71.4%]; P = .002), and secondary operations for WCs were somewhat reduced (6 of 18 patients [33%] versus 13 of 30 patients [43%]; P = .55). Moderate edema, skin, subcutaneous, and joint toxicity was present in 6 (11.1%), 1 (1.9%), 5 (9.3%), and 3 (5.6%) patients, respectively, but there were no bone fractures. Four local recurrences (6.8%, none near the flaps) occurred with median follow-up of 49 months. CONCLUSIONS: The 30.5% incidence of WCs was numerically lower than the 43% risk derived from the National Cancer Institute of Canada SR2 trial, but did not reach statistical significance. Preoperative IG-IMRT significantly diminished the need for tissue transfer. RT chronic morbidities and the need for subsequent secondary operations for WCs were lowered, although not significantly, whereas good limb function was maintained.

Prophylactic antibiotic regimens in tumour surgery (PARITY): protocol for a multicentre randomised controlled study.

INTRODUCTION: Limb salvage with endoprosthetic reconstruction is the standard of care for the management of lower-extremity bone tumours in skeletally mature patients. The risk of deep postoperative infection in these procedures is high and the outcomes can be devastating. The most effective prophylactic antibiotic regimen remains unknown, and current clinical practice is highly varied. This trial will evaluate the effect of varying postoperative prophylactic antibiotic regimens on the incidence of deep infection following surgical excision and endoprosthetic reconstruction of lower-extremity bone tumours. METHODS AND ANALYSIS: This is a multicentre, blinded, randomised controlled trial, using a parallel two-arm design. 920 patients 15 years of age or older from 12 tertiary care centres across Canada and the USA who are undergoing surgical excision and endoprosthetic reconstruction of a primary bone tumour will receive either short (24 h) or long (5 days) duration postoperative antibiotics. Exclusion criteria include prior surgery or infection within the planned operative field, known colonisation with methicillin-resistant Staphylococcus aureus or vancomycin-resistant Enterococcus at enrolment, or allergy to the study antibiotics. The primary outcome will be rates of deep postoperative infections in each arm. Secondary outcomes will include type and frequency of antibiotic-related adverse events, patient functional outcomes and quality-of-life scores, reoperation and mortality. Randomisation will be blocked, with block sizes known only to the methods centre responsible for randomisation, and stratified by location of tumour and study centre. Patients, care givers and a Central Adjudication Committee will be blinded to treatment allocation. The analysis to compare groups will be performed using Cox regression and log-rank tests to compare survival functions at α=0.05. ETHICS AND DISSEMINATION: This study has ethics approval from the McMaster University/Hamilton Health Sciences Research Ethics Board (REB# 12-009). Successful completion will significantly impact on clinical practice and enhance patients' lives. More broadly, this trial will develop a network of collaboration from which further high-quality trials in Orthopaedic Oncology will follow.

Effects of neoadjuvant chemotherapy on image-directed planning of surgical resection for distal femoral osteosarcoma.

BACKGROUND: Standard therapy for localized osteosarcoma includes neoadjuvant chemotherapy preceding local control surgery, followed by adjuvant chemotherapy. When limb-salvage procedures were being developed, preoperative chemotherapy allowed a delay in definitive surgery to permit fabrication of custom endoprosthetic reconstruction implants. One rationale for its continuation as the care standard has been the perception that it renders surgery easier and safer. Our objective was to compare surgical procedures planned on the basis of magnetic resonance images (MRIs) of distal femoral osteosarcomas acquired before neoadjuvant chemotherapy with surgical procedures planned on the basis of MRIs acquired after neoadjuvant chemotherapy as a measure of the surgically critical anatomic effects of the chemotherapy. METHODS: Twenty-four consecutive patients with distal femoral osteosarcoma had available digital MRIs preceding and following neoadjuvant chemotherapy. Thorough questionnaires were used to catalogue surgically critical anatomic details of MRI-directed surgical planning. Four faculty musculoskeletal oncologic surgeons and two musculoskeletal radiologists evaluated the blinded and randomly ordered MRIs. Interrater and intrarater reliabilities were calculated with intraclass correlation coefficients. The Student t test and chi-square test were used to compare pre-chemotherapy and post-chemotherapy continuous and categorical variables on the questionnaire. Mixed-effect regression models were employed to compare surgical procedures planned on the basis of pre-chemotherapy MRIs and with those planned on the basis of post-chemotherapy MRIs. RESULTS: The blinded reviews generated strong intraclass correlation coefficients for both interrater (0.772) and mean intrarater (0.778) reliability. The MRI-planned resections for the majority of tumors changed meaningfully after chemotherapy, but in inconsistent directions. On the basis of mixed-effect regression modeling, it appeared that more amputations were planned on the basis of post-chemotherapy MRIs. No other parameters differed in a significant and clinically meaningful fashion. Surgeons demonstrated their expectation that neoadjuvant chemotherapy would improve resectability by planning more radical surgical procedures on the basis of scans that they predicted had been obtained pre-chemotherapy. CONCLUSIONS: Surgeons can reliably record the anatomic details of a planned resection of an osteosarcoma. Such methods may be useful in future multi-institutional clinical trials or registries. The common belief that neoadjuvant chemotherapy increases the resectability of extremity osteosarcomas remains anecdotally based. Rigorous assessment of this phenomenon in larger cohorts and at other anatomic sites as well as re-evaluation of other arguments for neoadjuvant chemotherapy should be considered.

Prophylactic antibiotic regimens in tumor surgery (PARITY) survey.

BACKGROUND: Deep infection following endoprosthetic limb reconstruction for sarcoma of the long bones is a devastating complication occurring in 15% of sarcoma patients. Optimizing infection protocols and conducting definitive surgical trials are critical to improving outcomes. In this study, the PARITY (Prophylactic Antibiotic Regimens in Tumor Surgery) investigators aimed to examine surgeon preferences in antibiotic prophylaxis and perceptions about current evidence, as well as to ascertain interest in resolving uncertainty in the evidence with clinical trials. METHODS: We used a cross-sectional survey to examine current practice in the prescription of prophylactic antibiotics in Musculoskeletal Tumor Surgery. The survey was approved by our institution's Ethics Board and emailed to all Active Members of the Musculoskeletal Tumor Society (MSTS) and Canadian Orthopaedic Oncology Society (CANOOS). Survey answers were collected using an anonymous online survey tool. RESULTS: Of the 96 surgeons who received the questionnaire, 72 responded (75% response rate (% CI: 65.5, 82.5%)). While almost all respondents agreed antibiotic regimens were important in reducing the risk of infection, respondents varied considerably in their choices of antibiotic regimens and dosages. Although 73% (95% CI: 61, 82%) of respondents prescribe a first generation cephalosporin, 25% favor additional coverage with an aminoglycoside and/or Vancomycin. Of those who prescribe a cephalosporin, 33% prescribe a dosage of one gram for all patients and the reminder prescribe up to 2 grams based on body weight. One in three surgeons (95% CI: 25, 48%) believes antibiotics could be discontinued after 24 hours but 40% (95% CI: 30, 53%) continue antibiotics until the suction drain is removed. Given the ongoing uncertainty in evidence to guide best practices, 90% (95% CI: 81, 95%) of respondents agreed that they would change their practice if a large randomized controlled trial showed clear benefit of an antibiotic drug regimen different from what they are currently using. Further support for a clinical trial was observed by an overwhelming surgeon interest (87%; 95% CI: 77, 93%) in participating in a multi-center randomized controlled study. CONCLUSION: The current lack of guidelines for the prescription of prophylactic antibiotics in Musculoskeletal Tumor Surgery has left Orthopaedic Oncologists with varying opinions and practices. The lack of current evidence and strong surgeon support for participating in a definitive study provides strong rationale for clinical trials.

Myxoid\round cell liposarcoma (MRCLS) revisited: an analysis of 418 primarily managed cases.

BACKGROUND: Objectives of this study were to evaluate oncologic outcomes and to provide guidelines for the management of primary myxoid (MLS) and round cell liposarcoma (RCLS). METHODS: A multicenter, retrospective study of 418 cases of MRCLS primarily managed by Canadian multidisciplinary sarcoma teams. RESULTS: Study included 418 cases (MLS: 311 patients and RCLS: 107; >5% round cell) with a median age of 45 years and a median follow-up of 5.2 years. Median tumor size was 10 cm, and 81% were deep and 90% were in lower limb. The majority of patients underwent surgical resection and radiotherapy, with a small percentage (6%) receiving chemotherapy. The overall 10-year local control rate was 93% with no differences between MLS and RCLS. Radiotherapy was significant in preventing local relapse and reducing tumor diameter (median=18%) and improving microscopic margin status, but did not impact survival. Radiotherapy and the margin status were independent predictors of local recurrence. The 5- and 10-year metastatic-free survivals were 84 and 77% respectively for MLS and 69 and 46% for RCLS. The initial site of metastasis was found in multiple locations (34%) and bone involvement was frequent (40%) with predilection for spine (79%). Round cell percent (>5%) and tumor diameter (>10 cm) correlated with increased risk for metastasis and death. CONCLUSIONS: MLS and RCLS showed different metastatic risk but equally good local control. Radiotherapy was effective in preventing local recurrence and should be delivered as neoadjuvant. New staging strategies are to be defined to account for the unusual metastatic pattern.

Patient-oriented functional results of total femoral endoprosthetic reconstruction following oncologic resection.

BACKGROUND AND OBJECTIVES: Functional outcomes following oncologic total femoral endoprosthetic reconstruction (TFR) are lacking. We compared patient-oriented functional results of TFRs to proximal femur and distal femur reconstructions (PFR and DFR). We also compared function and complications with regard to knee and hip componentry. METHODS: Fifty-four TFR patients were identified from three institutional prospective databases. Forty-one had fixed- and 13 had rotating-hinge knees, 37 hemiarthroplasty and 17 total hip arthroplasty componentry. Toronto Extremity Salvage Scores (TESS) for n = 27 were compared between groups and to cohorts of PFR (n = 31) and DFR (n = 85) patients using the Mann-Whitney U-test. RESULTS: Follow-up averaged 4 years. Mechanical complications included five hip dislocations and one femoral malrotation. Four dislocations were in fixed-hinge implants, all in those lacking abductor reattachment. TESS averaged 69.3 ± 17.8, statistically decreased from DFR (P = 0.002) and PFR patients (P = 0.036). No significant differences were detected between patients in the fixed-hinge (n = 18) and rotating-hinge (n = 9) groups (P = 0.944), or total hip (n = 8) and hemiarthroplasty (n = 19) groups (P = 0.633). CONCLUSIONS: TFR is reserved for extreme cases of limb salvage, portending a poor prognosis overall. Function reflects additive impairments from PFR and DFR. TFR outcomes differ little with rotating- or fixed-hinge, total hip or hemiarthroplasty implants.

A biomechanical evaluation of press-fit stem constructs for tumor endoprosthetic reconstruction of the distal femur.

This study was designed to assess the biomechanical parameters of the older Kotz Modular Femur Tibia Reconstruction (Stryker Inc, Mahwah, NJ) stem and the newer Restoration and the unfluted Global Modular Replacement System (Stryker Inc, Mahwah, NJ) uncemented stems for use with tumor endoprostheses as well as to assess the optimal reaming technique for insertion of these stems. Fresh-frozen adult femora or composite distal femora were implanted with the uncemented stems. Separate experiments were performed to compare reaming technique and bone resection level. All constructs were mechanically tested for axial compression, lateral bending, and torsional stiffness and torque to failure. Results showed that the biomechanical performance of all the stems were similar with respect to each parameter. Cylindrical reaming was associated with a significantly higher torque to failure than flexible reaming in the diaphysis (P = .006). Newer uncemented stems provide adequate initial biomechanical stability for implantation in the distal femur.

Soft tissue sarcoma presenting with metastatic disease: outcome with primary surgical resection.

BACKGROUND: The objective of this study was to assess patient, tumor, and treatment factors that affected overall survival in a group of patients who underwent surgery for soft tissue sarcoma (STS) and presented with American Joint Commission on Cancer stage IV disease. METHODS: A retrospective review was undertaken of a single institution's database from the years 1986 to 2006 in all patients who met the following inclusion criteria: 1) surgical management of the primary tumor was undertaken, and 2) metastatic disease was present at the time of initial presentation. In total, 112 patients were identified who met the inclusion criteria. RESULTS: The 5-year survival rate for the entire group was 17%. In univariate analysis, the variables that were identified as statistically significant for predicting improved overall survival were resection of metastatic disease (P = .003), <4 pulmonary metastases (P = .05), and the presence of lymph node metastases versus pulmonary metastases (P = .0002). In multivariate analysis, only the presence of lymph node metastases versus pulmonary metastases retained statistical significance (P = .05). The 5-year survival rate for patients who had lymph nodes metastases at diagnosis was 59%, whereas it was only 8% for patients who presented with pulmonary metastases. CONCLUSIONS: Patients who presented with metastatic STS had a very poor prognosis despite aggressive surgical management of their primary tumor. The current results indicated that, although patients with isolated lymph node metastases may be cured by surgical resection, patients with pulmonary metastases are unlikely to be cured even with aggressive surgical management and should be treated with palliation of symptoms as the main objective.

Clinical and functional outcomes of patients with a pathologic fracture in high-grade osteosarcoma.

BACKGROUND AND OBJECTIVES: There have been variable reports of outcomes of patients with osteosarcoma and pathologic fractures. The purpose of this study was to document outcomes after management of this clinical entity at a single large oncology center. METHODS: A retrospective review was undertaken of our database between 1989 and 2006. We compared oncologic and functional outcomes of 201 patients with high-grade osteosarcoma without pathologic fractures to 31 patients with pathologic fractures. RESULTS: The rate of amputation in the group with pathologic fracture was significantly higher than the group without fracture (39% vs. 14%, P = 0.001). There was no difference in the rate of local recurrence between groups. The 5-year survival was superior in the group without pathologic fracture (60% vs. 41%, P = 0.0015). For patients with localized disease, 5-year survival was higher in patients without fracture (68% vs. 52%, P = 0.006). Disability as measured by the Toronto Extremity Salvage Score was no different between the groups. Impairment as measured by the Musculoskeletal Tumor Society scores was lower in the group without fracture. CONCLUSIONS: Presentation with a pathologic fracture in osteosarcoma did not preclude limb salvage surgery in a majority of patients, did not increase the risk of local recurrence, but was associated with poorer overall survival.