Physeal Bystander Effects in Rhabdomyosarcoma Radiotherapy: Experiments in a New Xenograft Model

Radiotherapy used in the treatment of pediatric musculoskeletal sarcomas may result in crippling defects of skeletal growth. Several radioprotective strategies have shown potential for preserving function of the irradiated epiphysis but have not been evaluated in a tumor-bearing animal model. We developed two bioluminescent human rhabdomyosarcoma cell lines that were used to establish xenograft tumors in skeletally immature mice. Bioluminescence imaging and radiography allowed serial evaluation of tumor growth and tibial elongation following localized radiotherapy. High-dose (10 Gy) radiotherapy significantly reduced tumor growth velocity and prolonged the median survival of tumor-bearing mice but also resulted in a significant 3.3% shortening of the irradiated limb. Exposure to a lower, 2 Gy dose resulted in 4.1% decrease in limb length but did not extend survival. This new model provides a clinically relevant means to test the efficacy and safety of novel radioprotectant and radiorecovery strategies for use in this context

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

IntroductionLimb 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 analysisThis 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 disseminationThis 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

Proximal humerus reconstruction in orthopedic oncology

Proximal humeral reconstructive options following radical resection of proximal humeral primary and metastatic bone malignancies have evolved over time. With the relatively recent advent of the reverse total shoulder (RTSA), this technique has been increasingly employed in this setting over hemiarthroplasty techniques. An array of options, including proximal humeral allograft-prosthetic composites (including both RTSA and hemiarthroplasty), megaprostheses, and osteoarticular allografts, is reviewed from the perspective of their indications, techniques, complications, and published results. An extensive case-based pictorial presentation illustrates these options

Evidence of Negative Effects of Defect Size and Older Patient Age by Quantitative CT-Based 3D Image Analysis in Ultraporous Beta-Tricalcium Phosphate Grafted Extremity Bone Defects at One Year

Introduction. Synthetic bone graft materials are commonly used to fill defects after curettage of benign bone lesions. Ultraporous beta tricalcium phosphate (TCP) is a popular synthetic compound used in this situation. Prior clinical studies based on plain X-ray analysis suggest incorporation of TCP is incomplete, even when combined with bone marrow (BMA). Purpose. The purpose was to analyze volumetric CT-based changes in defects grafted with TCP with/without BMA in a completed prospective RCT to objectively determine (1) relationship between size and age versus TCP incorporation and (2) whether there is an advantage to addition of BMA. Methods. Twenty-one patients with CT scans at ≥1 year follow-up available for digital analysis (TCP=10, TCP w/BMA =11) form the study population. CT image stacks were evaluated by creating volumetric masks using MIMICS imaging software for total defect, graft remaining, and graft incorporated volumes graft incorporation endpoints. Results. Overall, there was significant (p=0.0029) negative correlation (r2 = 0.38) between defect size and ratio of incorporated bone to defect size. This relationship remained strong (r2 = 0.56) particularly for defects > 20 cc but not for smaller defects. Bone width was also a significantly related factor (r2 = 0.94), with less graft incorporation in larger bone sites, in part likely due to the linear relationship between defect size and bone width. Relationship with age was complex and closely tied to defect volume. For larger defect volumes, younger patients were more successful at graft incorporation. Although age itself was not an independently significant factor, as defect volume increased, advanced age more negatively impacted new bone formation. Conclusions. Larger size defect and affected bone and advancing age appear to be important negative factors in synthetic graft incorporation. Results showed no advantage to addition of BMA to TCP

Atypical Enostoses—Series of Ten Cases and Literature Review

Bone islands (BI; enostoses) may be solitary or occur in the setting of osteopoikilosis (multiple bone islands) and are sometimes associated with Gardner’s Syndrome (osteopoikilosis and colonic polyposis). Characteristic features of bone islands are (1) absence of pain or local tenderness, (2) typical radio dense central appearance with peripheral radiating spicules (rose thorn), (3) Mean CT (computerized tomography) attenuation values above 885 Hounsfield units (HU) (4) absence of uptake on bone scan and (5) radiographic stability over time. However, when enostoses display atypical features of pain, unusual radiographic appearance, aberrant HU, increased radiotracer uptake, and/or enlargement, they can be difficult to differentiate from more sinister bony lesions such as osteoblastic metastasis, low grade central osteosarcoma, osteoid osteoma and osteoblastoma. In this retrospective case series, the demographic, clinical, radiographic, treatment and outcome for ten patients with eleven atypical bone islands (ABI) are presented, some showing associated pain (5), some with atypical radiographic appearance (3), some with increased activity on BS (4), some with documented enlargement over time (7), one with abnormal CT attenuation value, some in the setting of osteopoikilosis (2), one in the setting of Gardner’s Syndrome and one osteoid osteoma simulating a bone island. This series represents the spectrum of presentations of ABI. Comprehensive review of the literature reveals that the previous largest series of ABI showing enlargement as the atypical feature was in younger patients with jaw BI. Hence, this represents one of the largest series reported of ABI of all types in adults

Right Biceps Pseudo-Tumor from COVID-19 Vaccination

Delayed hypersensitivity reactions (DHRs) have been reported in association with COVID-19 vaccines, particularly those that are mRNA-based. Classic DHRs result in induration, erythema, tenderness, and urticaria. However, soft tissue mass is an uncommon complication of a COVID-19 vaccination-associated DHR and is rarely reported in the literature. We present a case of a 49-year-old male who recognized a mildly painful, firm soft tissue mass within the biceps mimicking neoplasm six months after receiving the booster dose of the Moderna vaccine. Non-operative conservative treatment modalities, including heating pads, ice packs, acetaminophen, and ibuprofen, failed to improve the patient’s mass. The mass, which proved histologically to be an inflammatory pseudo-tumor, did not recur after complete excision. While there have been many reported cases of DHRs following COVID-19 vaccinations, we present this case to raise awareness of the development of pseudo-tumors as a possible, yet rare, clinical manifestation of DHRs following vaccination