Are Skin Fiducials Comparable to Bone Fiducials for Registration When Planning Navigation-assisted Musculoskeletal Tumor Resections in a Cadaveric Simulated Tumor Model?

BACKGROUND: To improve and achieve adequate bony surgical margins, surgeons may consider computer-aided navigation a promising intraoperative tool, currently applied to a relatively few number of patients in whom freehand resections might be challenging. Placing fiducials (markers) in the bone, identifying specific anatomical landmarks, and registering patients for navigated resections are time consuming. To reduce the time both preoperatively and intraoperatively, skin fiducials may offer an efficient and alternative method of navigation registration. QUESTIONS/PURPOSES: (1) Does preoperative navigation using skin fiducials for registration allow the surgeon to achieve margins similar to those from bone fiducial registration in a simulated lower extremity tumor resection model in cadavers? (2) Does the use of preoperative navigation using skin fiducials for registration allow the surgeon to achieve similar bony margins in pelvic resections of simulated tumors as those achieved in long-bone resections using only skin fiducials for navigation in a cadaver model? METHODS: Simulated bone tumor resections were performed in three fresh-frozen cadavers with intact pelvic and lower-extremity anatomy using navigation guidance. We placed 5-cm intraosseous cement simulated bone tumors in the proximal/distal femur (n = 12), and proximal/distal tibia (n = 12) and pelvis (supraacetabular; n = 6). After bone tumor implantation, CT images of the pelvis and lower extremities were obtained. Each planned osseous resection margin was set at 10 mm. Navigation registration was performed for each simulated tumor using bone and skin markers that act as a point of reference (fiducials). The simulated bone tumor was resected based on a resection line that was established with navigation, and the corresponding osseous margins were calculated after resection. These margins were determined by an orthopaedic surgeon who was blinded to resection planning by the removal of cancellous bone around the cement simulated tumor. The shortest distance was measured from the cement to the resection line. Smaller mean differences between planned and postoperative margins were considered accurate. Independent t-tests were conducted to assess measurement differences between planned and postoperative margins at the 95% CI. Bland-Altman analyses were conducted to compare the deviation in margin difference between planned and postoperative margins in skin and bone fiducial registration, respectively. RESULTS: In all, 84 total resection margins were measured with 48 long bone and 20 pelvic obtained with skin fiducials and 16 long bone obtained with bone fiducials. The planned mean margin was 10 mm for all long bone and pelvic resections. We found that skin fiducial and bone fiducial postoperative margins had comparable accuracy when resecting long bones (10 ± 2 mm versus 9 ± 2 mm, mean difference 1 [95% CI 0 to 2]; p = 0.16). Additionally, skin fiducial long bone postoperative margins were comparable in accuracy to pelvic supraacetabular postoperative margins obtained with skin fiducials (10 ± 2 mm versus 11 ± 3 mm, mean difference -1 mm [95% CI -3 to 1]; p = 0.22). When comparing the deviation in margin difference between planned and postoperative margins in skin and bone fiducial registration, 90% (61 of 68) of skin fiducial and 100% (16 of 16) bone fiducial postoperative margins fell within 2 SDs. CONCLUSIONS: In this pilot study, skin fiducial markers were easy to identify on the skin surface of the cadaver model and on CT images used to plan margins. This technique appears to be an accurate way to plan margins in this model, but it needs to be tested thoroughly in patients to determine if it may be a better clinical approach than with bone fiducials. CLINICAL RELEVANCE: The margins obtained using skin fiducials and bone fiducials for registration were similar and comparable in this pilot study with a very small effect size. Boundaries of the simulated tumors were not violated in any resections. Skin fiducials are easier to identify than bone fiducials (anatomic landmarks). If future clinical studies demonstrate that margins obtained using skin fiducials for registration are similar to margins obtained with anatomical landmarks, the use of navigation with skin fiducials instead of bone fiducials may be advantageous. This technique may decrease the surgeon's time used to plan for and localize registration points and offer an alternative registration technique, providing the surgeon with other registration approaches.

MRI Identification of the Osseous Extent of Pediatric Bone Sarcomas.

BACKGROUND: The quantitative accuracy of MRI in predicting the intraosseous extent of primary sarcoma of bone has not been definitively confirmed, although MRI is widely accepted as an accurate tool to plan limb salvage resections. Because inaccuracies in MRI determination of tumor extent could affect the ability of a tumor surgeon to achieve negative margins and avoid local recurrence, we thought it important to assess the accuracy of MR-determined tumor extent to the actual extent observed pathologically from resected specimens in pediatric patients treated for primary sarcomas of bone. QUESTIONS/PURPOSES: (1) Does the quantitative pathologic bony margin correlate with that measured on preoperative MRI? (2) Are T1- or T2-weighted MRIs most accurate in determining a margin? (3) Is there a difference in predicting tumor extent between MRI obtained before or after neoadjuvant chemotherapy and which is most accurate? METHODS: We retrospectively studied a population of 211 potentially eligible patients who were treated with limb salvage surgery between August 1999 and July 2015 by a single surgeon at a single institution for primary sarcoma of bone. Of 131 patients (62%) with disease involving the femur or tibia, 107 (51%) were classified with Ewing's sarcoma or osteosarcoma. Records were available for review in our online database for 79 eligible patients (37%). Twenty-six patients (12%) were excluded because of insufficient or unavailable clinical or pathology data and 17 patients (8%) were excluded as a result of inadequate or incomplete MR imaging, leaving 55 eligible participants (26%) in the final cohort. The length of the resected specimen was superimposed on preresection MRI sequences to compare the margin measured by MRI with the margin measured by histopathology. Arithmetic mean differences and Pearson r correlations were used to assess quantitative accuracy (size of the margin). RESULTS: All MR imaging types were positively associated with final histopathologic margin. T1-weighted MRI after neoadjuvant chemotherapy and final histopathologic margin had the strongest positive correlation of all MR imaging and time point comparisons (r = 0.846, p < 0.001). Mean differences existed between the normal marrow margin on T1-weighted MRI before neoadjuvant chemotherapy (t = 8.363; mean, 18.883 mm; 95% confidence interval [CI], 14.327-23.441; p < 0.001), T2-weighted MRI before neoadjuvant chemotherapy (t = 8.194; mean, 17.204 mm; 95% CI, 12.970-21.439; p < 0.001), T1-weighted after neoadjuvant chemotherapy (t = 10.808; mean, 22.178 mm; 95% CI, 18.042-26.313; p < 0.001), T2-weighted after neoadjuvant chemotherapy (t = 10.702; mean, 20.778 mm; 95% CI, 16.865-24.691; p < 0.001), and the final histopathologic margin. T1-weighted MRI after neoadjuvant chemotherapy compared with the final histopathologic margin had the smallest mean difference in MRI-measured versus histopathologic margin size (mean, 5.9 mm; SD = 4.5 mm). CONCLUSIONS: T1 MRI after neoadjuvant chemotherapy exhibited the strongest positive correlation and smallest mean difference compared with histopathologic margin. When planning surgical resections based on MRI obtained after neoadjuvant chemotherapy, for safety, one should account for a potential difference between the apparent margin of a tumor on an MRI and the actual pathologic margin of that tumor of up to 1 cm. LEVEL OF EVIDENCE: Level III, diagnostic study.

Can a Made-for-Consumer Activity Monitor Assess Physical Activity in Adolescents and Young Adults After Lower Extremity Limb Salvage for Osseous Tumors?

BACKGROUND: The purpose of this study was to test the validity of a consumer-oriented activity monitor in adolescents and young adults undergoing limb salvage for primary bone malignancies. METHODS: A cross-sectional population of participants with an average age of 16 (range 12 to 22) years produced 472 days of activity monitoring during 25 evaluations periods alongside patient-reported outcome measures. RESULTS: Average daily steps ranged from 557 to 12,756 (mean=4711) and was moderately associated with the short-form (SF) 36 physical component subscale (r=0.46, P=0.04) as well as the SF6D health state utility measure (r=0.48, P=0.04), but not the SF36 mental component subscale (P=0.66) or Toronto extremity salvage score (P=0.07). Time from surgery was strongly correlated with average daily steps (r=0.7, P<0.001). CONCLUSIONS: A made-for-consumer activity monitor provided real-world data regarding the outcome of adolescent and young adult limb salvage, and evidence of validity in this population. Such lower cost, user-friendly devices may facilitate assessment of free-living activity and allow novel comparisons of treatment strategies. LEVEL OF EVIDENCE: Level II-diagnostic.

Soft Tissue Sarcoma, Version 2.2016, NCCN Clinical Practice Guidelines in Oncology.

Soft tissue sarcomas (STS) are rare solid tumors of mesenchymal cell origin that display a heterogenous mix of clinical and pathologic characteristics. STS can develop from fat, muscle, nerves, blood vessels, and other connective tissues. The evaluation and treatment of patients with STS requires a multidisciplinary team with demonstrated expertise in the management of these tumors. The complete NCCN Guidelines for Soft Tissue Sarcoma (available at NCCN.org) provide recommendations for the diagnosis, evaluation, and treatment of extremity/superficial trunk/head and neck STS, as well as intra-abdominal/retroperitoneal STS, gastrointestinal stromal tumor, desmoid tumors, and rhabdomyosarcoma. This manuscript discusses guiding principles for the diagnosis and staging of STS and evidence for treatment modalities that include surgery, radiation, chemoradiation, chemotherapy, and targeted therapy.

The effect of surgery with radiation on pelvic Ewing sarcoma survival.

BACKGROUND: Pelvic Ewing sarcoma (ES) has poorer outcomes than extremity-based lesions and the method of local control is controversial. METHODS: A retrospective review was performed of 40 primary pelvic or sacral ES treated by a single surgeon. All received modern chemotherapy and those that received radiation were treated with modern dosages. RESULTS: Fifty-five percent were disease-free at latest follow-up (median, 83.1 mos). Sixty-one percent had ≥ 99% necrosis, which was associated with 65% disease-free survival. Larger size (P = 0.016) and the absence of metastatic disease (P = 0.005) was predictive of survival. Eighty-three percent of relapsed patients were DOD. Half of patients who received surgery alone or RT alone have NED while 57% of those who received S/RT have NED. Complication rates were 69% (S/RT), 75% (surgery alone), 10% (RT alone). Functional outcomes were similar. CONCLUSION: Primary pelvic ES is localized at presentation in 50% and the absence of metastases is the strongest predictor for survival. Chemotherapy is key, but excellent histologic response is neither a guarantee nor a necessity for survival. More than one-third die despite an excellent histologic response and at least one-third with lung metastases survive. With chemotherapy, radiation, and surgery, reasonable control of disease can be achieved. LEVEL OF EVIDENCE III: Case-control or retrospective cohort study.

Soft tissue sarcoma, version 2.2014.

These NCCN Guidelines Insights highlight the important updates to the NCCN Guidelines for Soft Tissue Sarcoma (STS) specific to the role of radiation therapy in the management of patients with retroperitoneal/intra-abdominal STS. The guidelines have also included recommendations for genetic testing and counseling for patients with a clinical and/or family history of genetic cancer syndromes associated with a predisposition for the development of STS.

Gastrointestinal stromal tumors, version 2.2014.

Gastrointestinal stromal tumors (GIST) are the most common soft tissue sarcoma of the gastrointestinal tract, resulting most commonly from KIT or platelet-derived growth factor receptor α (PDGFRα)-activating mutations. These NCCN Guideline Insights highlight the important updates to the NCCN Guidelines for Soft Tissue Sarcoma specific to the management of patients with GIST experiencing disease progression while on imatinib and/or sunitinib.

NY-ESO-1 is a ubiquitous immunotherapeutic target antigen for patients with myxoid/round cell liposarcoma.

BACKGROUND: Myxoid/round cell liposarcoma (MRCL) is the second most common liposarcoma subtype, accounting for >33% of liposarcomas and approximately 10% of all soft tissue sarcomas. Although MRCL is a chemosensitive subtype, patients with metastatic disease have a poor outcome. NY-ESO-1 is a cancer-testis antigen (also known as cancer germ cell antigen) that has been successfully targeted in vaccine trials and in adoptive T-cell therapy trials for the treatment of several solid tumors. METHODS: The authors investigated the feasibility of targeting NY-ESO-1 in patients with MRCL by evaluating the prevalence of NY-ESO-1 expression in tumors using immunohistochemistry and quantitative reverse transcriptase-polymerase chain reaction analysis. NY-ESO-1-specific tumor recognition by NY-ESO-1-specific T-cells also was analyzed using a chromium release assay. RESULTS: A search of the University of Washington Sarcoma Tissue Bank identified paraffin-embedded tumor samples from 25 patients with MRCL. NY-ESO-1 expression was observed in every MRCL tumor assessed (100%); in 18 tumors (72%), staining was homogenous. In all but 2 tumors, staining was sufficiently robust (2+) that such patients would be eligible for clinical trials of NY-ESO-1-directed therapy. By using NY-ESO-1 specific, CD8-positive T-cells, the in vitro sensitivity of myxoid liposarcoma cell lines to antigen-specific lysis was demonstrated. CONCLUSIONS: The current results establish NY-ESO-1 as an important target antigen for the treatment of patients with MRCL.

Physical activity assessment in adolescents with limb salvage.

OBJECTIVES: To evaluate ambulatory activity differences between youth with limb salvage procedures and typically developing youth (TDY) and assess differences in self-reported activity levels in the 2 groups, to provide a basis for physical activity assessment in patients who had undergone limb salvage surgery and treatment planning that incorporates regaining normal physical and daily living activities. STUDY DESIGN: In this cohort comparison study, we compared ambulatory and self-reported activity levels in 20 youth (aged 11.7-20.8 years) who had undergone limb salvage surgery and a sex- and age-matched comparison cohort of 20 TDY. StepWatch activity monitor and Activity Scale for Kids data were used to answer these questions. RESULTS: Significant differences were found between the youth who had undergone limb salvage surgery and the TDY in total time active each day (43% vs 48%; P = .03), median total strides per day (4487 vs 7671; P = .001), and amount of time per day at high activity levels (20 minutes vs 47 minutes; P = .001). Self-reported overall physical activity, locomotion, and standing Activity Scale for Kids subscale scores were significantly lower in the youth undergoing limb salvage surgery compared with the TDY (summary score, 88.3 vs 97.7; P = .001). CONCLUSION: Patients undergoing limb salvage surgery exhibit reduced physical activity compared with normal age-matched controls.

Soft tissue sarcoma, version 2.2012: featured updates to the NCCN guidelines.

The major changes to the 2012 and 2011 NCCN Guidelines for Soft Tissue Sarcoma pertain to the management of patients with gastrointestinal stromal tumors (GISTs) and desmoid tumors (aggressive fibromatosis). Postoperative imatinib following complete resection for primary GIST with no preoperative imatinib is now included as a category 1 recommendation for patients with intermediate or high risk of recurrence. The panel also reaffirmed the recommendation for preoperative use of imatinib in patients with GISTs that are resectable with negative margins but associated with significant surgical morbidity. Observation was included as an option for patients with resectable desmoid tumors that are small and asymptomatic, not causing morbidity, pain, or functional limitation. Sorafenib is included as an option for systemic therapy for patients with desmoid tumors.

Body mass index (BMI) at diagnosis is associated with surgical wound complications in patients with localized osteosarcoma: a report from the Children's Oncology Group.

BACKGROUND: Malnutrition is common at diagnosis and during treatment for sarcoma patients. Poor nutritional status is associated with increased risk of complications, particularly infections. We investigated the role of body mass index (BMI) on the incidence of surgical wound complications in patients with localized osteosarcoma treated on the Children's Oncology Group (COG) legacy trial, INT-0133. PROCEDURE: Patients considered in this report had localized osteosarcoma, enrolled on COG trial INT-0133, remained on protocol therapy to have definitive surgery 6-16 weeks after study entry, and had adequate height, weight, and surgical complication data for analysis. By protocol design, definitive surgical resection was planned for 10 weeks after induction chemotherapy. Wound complications within 30 days after definitive surgery were considered post-operative. BMI was calculated at the start of neoadjuvant chemotherapy and expressed as age- and gender-adjusted percentile. The incidence of wound complications was evaluated by logistic regression or Fisher's exact test. RESULTS: A total of 498 patients met criteria for analysis. Low BMI (≤10th percentile) was seen in 73 (14.7%), middle BMI (11th-94th percentile) in 382 (76.7%), and high BMI (≥95th percentile) in 43 (8.6%) patients. Wound infection or slough was seen in low BMI patients (OR = 2.0, P = 0.07) although the results did not reach statistical significance. Arterial thrombosis was more common in high BMI patients (OR = 9.4, P = 0.03). CONCLUSIONS: Abnormal BMI at the start of treatment for localized osteosarcoma is associated with increased risk of post-operative wound complications such as arterial thrombosis. Future studies should evaluate whether maintenance of age-appropriate BMI reduces the risk of surgical complications.

Multiple myeloma: diagnosis and orthopaedic implications.

Multiple myeloma is a hematologic malignancy that commonly affects the skeletal system. The disease is primarily managed medically with chemotherapeutic agents. Pathologic fractures are common in patients with diagnosed and undiagnosed disease. The number of patients diagnosed with multiple myeloma is increasing, as is the incidence of associated pathologic fractures. Novel chemotherapeutic agents and radiation therapy protocols have been used to extend the average life span of patients with this disease. Various methods that allow for restoration of function and pain reduction can be used to stabilize and manage fractures associated with multiple myeloma. The orthopaedic surgeon and oncology team must work together to develop an individualized treatment plan to improve patient quality of life and provide pain relief.

Malignant progression in two children with multiple osteochondromas.

Multiple Osteochondromas (MO) is a disease of benign bony growths with a low incidence of malignant transformation. Secondary chondrosarcoma in children is rare even in children with MO. Making a diagnosis of malignancy in low-grade cartilage tumors is challenging and requires consideration of clinical, radiographic, and histopathological factors. We report two cases of skeletally immature patients with MO who presented with rapidly enlarging and radiographically aggressive lesions consistent with malignant transformation. Both underwent allograft reconstruction of the involved site with no signs of recurrence or metastatic disease at a minimum of four-year follow-up.

Histiocyte predominant myocarditis resulting from the addition of interferon gamma to cyclophosphamide-based lymphodepletion for adoptive cellular therapy.

BACKGROUND: Adoptive cellular therapy (ACT) is a promising treatment for synovial sarcoma (SS) with reported response rates of over 50%. However, more work is needed to obtain deeper and more durable responses. SS has a 'cold' tumor immune microenvironment with low levels of major histocompatibility complex (MHC) expression and few T-cell infiltrates, which could represent a barrier toward successful treatment with ACT. We previously demonstrated that both MHC expression and T-cell infiltration can be increased using systemic interferon gamma (IFN-γ), which could improve the efficacy of ACT for SS. CASE PRESENTATION: We launched a phase I trial incorporating four weekly doses of IFN-γ in an ACT regimen of high-dose cyclophosphamide (HD Cy), NY-ESO-1-specific T cells, and postinfusion low-dose interleukin (IL)-2. Two patients were treated. While one patient had significant tumor regression and resultant clinical benefit, the other patient suffered a fatal histiocytic myocarditis. Therefore, this cohort was terminated for safety concerns. CONCLUSION: We describe a new and serious toxicity of immunotherapy from IFN-γ combined with HD Cy-based lymphodepletion and low-dose IL-2. While IFN-γ should not be used concurrently with HD Cy or with low dose IL-2, IFN-γ may still be important in sensitizing SS for ACT. Future studies should avoid using IFN-γ during the immediate period before/after cell infusion. TRIAL REGISTRATION NUMBERS: NCT04177021, NCT01957709, and NCT03063632.

Risk assessment based on FDG-PET imaging in patients with synovial sarcoma.

UNLABELLED: Synovial sarcoma generally is associated with poor prognosis. With recent advances in molecular biology, it has become apparent not all synovial sarcomas share the same tumor biology. (18)F-fluorodeoxyglucose positron emission tomography (FDG-PET) is useful for risk assessment in several types of sarcomas. We therefore assessed the clinical value of (18)F-FDG-PET-derived maximum standard uptake value (SUV(max)) for predicting survival in patients with synovial sarcoma. (18)F-FDG-PET was performed in 44 patients with synovial sarcoma before therapy and resection. SUV(max) was calculated for each tumor and then evaluated for prognostic usefulness along with metastasis at presentation, tumor grade, histopathologic subtype, age, gender, postsurgical margins, anatomic location, and tumor size for overall survival and progression-free survival. SUV(max) ranged from 1.2 to 13.0 (median, 4.35). Pretherapy tumor SUV(max) predicted overall survival and progression-free survival. Patients presenting with a SUV(max) greater than 4.35 had a decreased disease-free survival and were therefore at high risk for having local recurrences and metastatic disease. LEVEL OF EVIDENCE: Level I, diagnostic study. See the Guidelines for Authors for a complete description of levels of evidence.

Megaprosthesis versus Condyle-sparing intercalary allograft: distal femoral sarcoma.

UNLABELLED: Although functionally appealing in preserving the native knee, the condyle-sparing intercalary allograft of the distal femur may be associated with a higher risk of tumor recurrence and endoprosthetic replacement for malignant distal femoral bone tumors. We therefore compared the risk of local tumor recurrence between patients in these two types of reconstruction groups. We retrospectively reviewed 85 patients (mean age, 22 years; range, 4-82 years), 38 (45%) of whom had a condyle-sparing allograft and 47 (55%) of whom had endoprostheses. The minimum followup for both groups was 2 years (mean, 7 years; range, 2-19 years). Local recurrences occurred in 11% (five of 47) of the patients having implants versus 18% (seven of 38) of the patients having allografts. Using time to local recurrence as an end point, the Kaplan-Meier survivorship of the implant group was similar to that of the condyle-sparing allograft group at 2, 5, and 10 years (93% versus 87% at 2 years, 87% versus 81% at 5 years, and 87% versus 81% at 10 years, respectively). The condyle-sparing allograft procedure offers the potential advantage of retaining the native knee in a young patient population while incurring no greater risk of local recurrence as those offered the endoprosthetic procedure. LEVEL OF EVIDENCE: Level IV, therapeutic study. See Guidelines for Authors for a complete description of levels of evidence.

Intraosseous malignant peripheral nerve sheath tumor of the sacrum in a patient with neurofibromatosis type I.

Malignant intraosseous peripheral nerve sheath tumor is a very rare malignancy most commonly seen in patients with neurofibromatosis type 1. This tumor almost exclusively occurs in the maxillofacial region, with manifestation of this tumor in other regions of the skeleton infrequently reported. We describe a 23-year-old female with previously undiagnosed neurofibromatosis type 1 presenting with lower extremity weakness, paresthesias, and bowel/bladder symptoms. The patient had an aneurysmal lytic bone lesion centered in the upper sacrum with invasion of the L5 vertebral body. On MRI, the lesion was homogeneously isointense to muscle on T1, heterogeneously hyperintense to muscle on T2, and demonstrated homogeneously avid contrast enhancement. Multiple additional small lesions with similar imaging characteristics were identified in the paraspinal soft tissues. Low grade malignant peripheral nerve sheath tumor of the sacrum was diagnosed on biopsy. The patient was treated with sacral resection and radiation therapy for local disease control.

Spatial heterogeneity in sarcoma 18F-FDG uptake as a predictor of patient outcome.

UNLABELLED: (18)F-FDG PET images of tumors often display highly heterogeneous spatial distribution of (18)F-FDG-positive pixels. We proposed that this heterogeneity in (18)F-FDG spatial distribution can be used to predict tumor biologic aggressiveness. This study presents data to support the hypothesis that a new heterogeneity-analysis algorithm applied to (18)F-FDG PET images of tumors in patients is predictive of patient outcome. METHODS: (18)F-FDG PET images from 238 patients with sarcoma were analyzed using a new algorithm for heterogeneity analysis in tumor (18)F-FDG spatial distribution. Patient characteristics, tumor histology, and patient outcome were compared with image analysis results using univariate and multivariate analysis. Cox proportional hazards models were used to further analyze the significance of the data associations. RESULTS: Statistical analyses show that heterogeneity analysis is a strong independent predictor of patient outcome. CONCLUSION: The new (18)F-FDG PET tumor image heterogeneity analysis method is validated for the ability to predict patient outcome in a clinical population of patients with sarcoma. This method can be extended to other PET image datasets in which heterogeneity in tissue uptake of a radiotracer may predict patient outcome.

Accuracy and Precision of a Surgical Navigation System: Effect of Camera and Patient Tracker Position and Number of Active Markers.

INTRODUCTION: Surgical navigation systems are increasingly used to aid resection and reconstruction of osseous malignancies. In the process of implementing image-based surgical navigation systems, there are numerous opportunities for error that may impact surgical outcome. This study aimed to examine modifiable sources of error in an idealized scenario, when using a bidirectional infrared surgical navigation system. MATERIALS AND METHODS: Accuracy and precision were assessed using a computerized-numerical-controlled (CNC) machined grid with known distances between indentations while varying: 1) the distance from the grid to the navigation camera (range 150 to 247cm), 2) the distance from the grid to the patient tracker device (range 20 to 40cm), and 3) whether the minimum or maximum number of bidirectional infrared markers were actively functioning. For each scenario, distances between grid points were measured at 10-mm increments between 10 and 120mm, with twelve measurements made at each distance. The accuracy outcome was the root mean square (RMS) error between the navigation system distance and the actual grid distance. To assess precision, four indentations were recorded six times for each scenario while also varying the angle of the navigation system pointer. The outcome for precision testing was the standard deviation of the distance between each measured point to the mean three-dimensional coordinate of the six points for each cluster. RESULTS: Univariate and multiple linear regression revealed that as the distance from the navigation camera to the grid increased, the RMS error increased (p<0.001). The RMS error also increased when not all infrared markers were actively tracking (p=0.03), and as the measured distance increased (p<0.001). In a multivariate model, these factors accounted for 58% of the overall variance in the RMS error. Standard deviations in repeated measures also increased when not all infrared markers were active (p<0.001), and as the distance between navigation camera and physical space increased (p=0.005). Location of the patient tracker did not affect accuracy (0.36) or precision (p=0.97). CONCLUSION: In our model laboratory test environment, the infrared bidirectional navigation system was more accurate and precise when the distance from the navigation camera to the physical (working) space was minimized and all bidirectional markers were active. These findings may require alterations in operating room setup and software changes to improve the performance of this system.

Malignant Transformation of Synovial Chondromatosis: A Systematic Review.

BACKGROUND: Synovial chondromatosis (SCh) can undergo malignant transformation. Pathologic diagnosis of secondary synovial chondrosarcoma (SChS) is challenging and misdiagnosis may result in over- or undertreatment. METHOD: A systematic review revealed 48 cases of SChS published in 27 reports since 1957. Data was collected to identify findings indicative of SChS and outcomes of treatment. RESULTS: At median follow-up of 18 months, patients were reported as alive (10%), alive without disease (22%), alive with disease (15%), dead of disease (19%), dead of pulmonary embolism (4%), and unknown (29%). Initial diagnosis of SChS (grade: low/unknown 48%, intermediate/high 52%) was after biopsy in 58%, local resection in 29%, and amputation in 13%. Seventy-four percent of patients underwent 1.8 (mean) resections. Patients treated prior to 1992 were managed with amputation in 79% of cases compared to 48% after 1992. Symptoms were present for 72 mos prior to diagnosis of SChS. Synovial chondrosarcoma demonstrated symptom progression over several months (82%), rapid recurrence after complete resection (30%), and medullary canal invasion (43%). The SChS tumor dimensions were seldom quantified. CONCLUSION: Malignant degeneration of synovial chondromatosis is rare but can necessitate morbid surgery or result in death. Pathognomonic signs for SChS including intramedullary infiltration are present in the minority of cases. Progression of symptoms, quick local recurrence, and muscle infiltration are more suggestive of SChS. Periarticular cortical erosion, extra-capsular extension, and metaplastic chondroid features are non-specific. Although poorly documented for SChS, tumor size is a strong indicator of malignancy. Biopsy and partial resection are prone to diagnostic error. Surgical decisions are frequently based on size and clinical appearance and may be in conflict with pathologic diagnosis.