Paul W. Clarkson

Combined Cementoplasty and Radiofrequency Ablation in the Treatment of Painful Neoplastic Lesions of Bone

PURPOSE To assess the safety and effectiveness of combined radiofrequency (RF) ablation and cementoplasty in the treatment of painful neoplastic lesions of bone. MATERIALS AND METHODS The authors performed a retrospective analysis of 25 combined treatments comprising RF ablation followed by injection of polymethylmethacrylate cement performed in 19 patients during a 22-month period. Patients ranged in age from 42 to 82 years (mean, 58.9 years) and included five women and 14 men. Eleven vertebrae (eight lumbar and three thoracic), nine acetabulae, three sacra, one pubis, and one humerus were treated with a total of 36 RF ablations (in several instances, overlapping ablations were used). The location of the primary neoplasm, lesion size, pain before and after the procedure (as determined with a 10-point visual analog scale [VAS]), number of RF treatments, type of device used for cementoplasty, RF time, cement volume, and extravasation were documented. RESULTS A total of 25 combined RF ablations and cementoplasties were performed. The technical success rate was 100% (25 of 25 treatments). There were seven minor complications: six limited cement extravasations and a transient thermal nerve injury. The mean RF time was 9.1 minutes (range, 6-12 minutes). The mean cement volume injected was 6.1 mL (range, 0.8-16 mL). The mean preprocedure pain (as measured with a VAS) was 7.9 (range, 7.0-9.0) and the mean posttreatment pain was 4.2 (range, 0-6); the difference was statistically significant (mean score, 4.08; 95% confidence interval: 3.92, 4.87; P < .0001) using a paired t test. CONCLUSIONS Combined RF ablation and cementoplasty appears to be safe and effective in the treatment of painful neoplastic lesions of bone.

Surgical Management of Primary Bone Tumors of the Spine: Validation of an Approach to Enhance Cure and Reduce Local Recurrence

Study Design. Multicenter ambispective cohort analysis. Objective. The purpose of this study is to determine whether applying Ennekings principles to surgical management of primary bone tumors of the spine significanti decreases local recurrence and/or mortality. Summary of Background Data. Oncologic management of primary tumors of spine has historically been inconsistent, controversial, and open to individual interpretation. Methods. A multicenter ambispective cohort analysis from 4 tertiary care spine referral centers was done. Patients were analyzed in 2 cohorts, “Enneking Appropriate” (EA), surgical margin as recommended by Enneking, and “Enneking Inappropriate” (EI), surgical margin not recommended by Enneking. Benign tumors were not included in mortality analysis. Results. Two cohorts represented an analytic dataset with 147 patients, 86 male, average age 46 years (range: 10-83). Median follow-up was 4 (2–7) years in the EA and 6 (5.5–15.5) years in the EI. Seventy-one patients suffered at least 1 local recurrence during the study, 57 of 77 in the EI group and 14 of 70 in the EA group. EI surgical approach caused higher risk of first local recurrence (P < 0.0001). There were 48 deaths in total; 29 in the EI group and 19 in the EA. There was a strong correlation between the first local recurrence and mortality with an odds ratio of 4.69, (P < 0.0001). EI surgical approach resulted in a higher risk of mortality with a hazard ratio of 3.10, (P = 0.0485) compared to EA approach. Conclusion. Surgery results in a significant reduction in local recurrence when primary bone tumors of the spine are resected with EA margins. Local recurrence has a high concordance with mortality in resection of these tumors. A significant decrease in mortality occurs when EA surgery is used.

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.

Epineural dissection is a safe technique that facilitates limb salvage surgery.

Epineural dissection has been used in our center for the past 19 years as a means of preserving the sciatic nerve when it is closely applied to a soft tissue sarcoma. Our aim in doing this study was to establish if this technique resulted in increased local or systemic recurrence of the tumor. In addition, we assessed functional outcomes. Forty-three patients had an epineural dissection done during primary resection of a malignant thigh tumor. These patients were compared with 44 patients with tumors that were of similar size and grade but distant from the nerve. We also analyzed seven patients who required nerve resection. There was no difference in local or systemic recurrence rates or functional outcomes when epineural dissection was done. Those with nerve resection had worse Musculoskeletal Tumor Society scores but equivalent Toronto Extremity Salvage Scores to those with an epineural dissection. We conclude that epineural dissection (when combined with radiotherapy in a planned multidisciplinary approach to limb salvage) is both a safe and effective procedure to preserve the sciatic nerve and that nerve resection should be limited to situations where the nerve is completely encased in tumor. Level of Evidence: Prognostic study, Level II-2 (retrospective cohort study). See the Guidelines for Authors for a complete description of levels of evidence.

Therapeutic Antibodies Targeting CSF1 Impede Macrophage Recruitment in a Xenograft Model of Tenosynovial Giant Cell Tumor

Tenosynovial giant cell tumor is a neoplastic disease of joints that can cause severe morbidity. Recurrences are common following local therapy, and no effective medical therapy currently exists. Recent work has demonstrated that all cases overexpress macrophage colony-stimulating factor (CSF1), usually as a consequence of an activating gene translocation, resulting in an influx of macrophages that form the bulk of the tumor. New anti-CSF1 drugs have been developed; however there are no preclinical models suitable for evaluation of drug benefits in this disease. In this paper, we describe a novel renal subcapsular xenograft model of tenosynovial giant cell tumor. Using this model, we demonstrate that an anti-CSF1 monoclonal antibody significantly inhibits host macrophage infiltration into this tumor. The results from this model support clinical trials of equivalent humanized agents and anti-CSF1R small molecule drugs in cases of tenosynovial giant cell tumor refractory to conventional local therapy.

Expression and stability of hypoxia inducible factor 1α in osteosarcoma

Hypoxia contributes to both physiological and pathological processes and its effects are mainly mediated through the transcription factors hypoxia‐inducible factor 1α and 2α (HIF1α and HIF2α). The purpose of this study was to examine the role of these proteins in osteosarcoma progression.

CT-Guided Percutaneous Cryoablation for Osteoid Osteoma: Initial Experience in Adults

OBJECTIVE The purpose of this study was to investigate the safety and efficacy of CT-guided percutaneous cryoablation for the treatment of osteoid osteoma in adults. MATERIALS AND METHODS A retrospective case series over a 30-month period involved 10 consecutive adult patients (nine male and one female patients; mean age, 27.9 years; age range, 16-49 years) who underwent CT-guided percutaneous cryoablation for management of osteoid osteoma. Clinical and technical success was evaluated with postprocedure MRI at 4-5 weeks and with digital numeric pain scores taken before and immediately after the procedure, as well as at primary follow-up (4-10 weeks; average, 5 weeks) and secondary follow-up (23-29 weeks; average, 24 weeks). RESULTS Clinical and technical success rates were 100%. Average digital numeric pain scores were 7.4 before the procedure, 1.5 after procedure, 0.5 at the primary follow-up, and 0.3 at secondary follow-up. No minor or major complications were noted during the procedure, recovery period, primary follow-up, or secondary follow-up. CONCLUSION CT-guided percutaneous cryoablation is safe and effective in the treatment of osteoid osteoma in adults.

Functional Results Following Vascularized Versus Nonvascularized Bone Grafts for Wrist Arthrodesis Following Excision of Giant Cell Tumors

PURPOSE Wrist arthrodesis after resection of a giant cell tumor of the distal radius can be performed using a vascularized free fibular transfer (VFFT) or a nonvascularized structural iliac crest transfer (NICT). The purpose of this study was to compare the union times, functional outcomes, and complications after these procedures. METHODS We identified 27 patients at 2 centers: 14 underwent VFFT, and 13 NICT. The 2 groups were comparable for age, sex, and tumor grade. We assessed functional outcomes of the wrist with the Toronto Extremity Salvage Score, Musculoskeletal Tumor Society 1987 and 1993 scores, and Disabilities of the Arm, Shoulder, and Hand scores. RESULTS Two local recurrences occurred in the VFFT group and 1 in the NICT group. The VFFT group had 3 patients who had already undergone or were planning to undergo surgery for improved appearance, hardware removal, or tendon release. In the NICT group, 2 infections required debridement, one of which went on to free fibular transfer, but there were no reoperations for nonunion or donor site morbidity. The surgical time was significantly shorter for NICT. Functional scores showed no differences between groups on any of the parameters studied for the upper limb. CONCLUSIONS Both VFFT and NICT were effective surgical techniques for wrist fusion after distal radial resection for giant cell tumor. Vascularized free fibular transfer should be considered when a major skin defect is anticipated, because it allows the inclusion of a vascularized skin paddle, or when the osseous defect is too long (> 10 cm) for NICT. We were unable to demonstrate a difference in upper limb functional scores between VFFT and NICT. Because the surgical time is significantly shorter and the reoperation rate is lower for NICT, we recommend NICT whenever possible. TYPE OF STUDY/LEVEL OF EVIDENCE Therapeutic III.

Small blue round cell tumor of the interosseous membrane bearing a t(2;22)(q34;q12)/EWS-CREB1 translocation: a case report

BackgroundThe group of small blue round cell tumors encompasses a heterogeneous group of neoplasms characterized by primitive appearing round cells with few distinguishing histologic features.ResultsWe report the case of a small blue round cell tumor with an EWS gene rearrangement detected by fluorescent in situ hybridization (FISH) analysis that mimicked Ewing sarcoma, but with unusual histology and immunohistochemical features. Multi-color karyotyping identified the presence of a t(2;22)(q34;q12) that was initially expected to represent a variant EWSR1-FEV translocation. After an extensive workup, the lesion is considered to represent a clear cell sarcoma harboring an EWSR1-CREB1 fusion transcript.ConclusionsThis case appears to represent a rare variant of clear cell sarcoma arising in peripheral soft tissues with unusual histology and unique immunophenotype. In this circumstance, FISH for all EWSR1 translocation partners or RT- PCR for a spectrum of possible transcript variants is critically important for diagnosis, since cytogenetic analysis or clinical FISH assay using only commercial EWSR1 probes will be misleading.

Tumor Endoprosthesis Revision Rates Increase With Peri-Operative Chemotherapy But Are Reduced With the Use of Cemented Implant Fixation

Chemotherapy may reduce osseointegration of tumor endoprosthesis, while delaying chemotherapy may reduce survival. We studied the effects of chemotherapy and cemented fixation on tumor endoprosthesis survivorship with a retrospective analysis of 50 consecutive patients receiving lower limb salvage surgery. We compared rates of radiographic loosening/revision and effect of cement fixation between chemotherapy/no chemotherapy cohorts. Chemotherapy increased the total revision rate (HR = 3.8 [1-14], P = 0.033), but did not affect aseptic loosening. Cement fixation reduced revision for loosening (HR = 0.09 (0.008-0.98), P = 0.012) and showed less radiographic loosening (HR = 0.09 (0.02-0.51), P = 0.00066). Cement fixation had lower rates of revision for loosening and radiographic loosening regardless of whether chemotherapy was given. We conclude that for these implants, cement fixation provides superior results to uncemented fixation.