Surgical Margins in Musculoskeletal Sarcoma.

¼ Negative margin resection of musculoskeletal sarcomas is associated with reduced risk of local recurrence.¼ There is limited evidence to support an absolute margin width of soft tissue or bone that correlates with reduced risk of local recurrence.¼ Factors intrinsic to the tumor, including histologic subtype, grade, growth pattern and neurovascular involvement impact margin status and local recurrence, and should be considered when evaluating a patient's individual risk after positive margins.¼ Appropriate use of adjuvant therapy, critical analysis of preoperative advanced cross-sectional imaging, and the involvement of a multidisciplinary team are essential to obtain negative margins when resecting sarcomas.

3D Specimen Scanning and Mapping in Musculoskeletal Oncology: A Feasibility Study.

BACKGROUND: Surgical resection is the primary treatment for bone and soft tissue tumors. Negative margin status is a key factor in prognosis. Given the three-dimensional (3D) anatomic complexity of musculoskeletal tumor specimens, communication of margin results between surgeons and pathologists is challenging. We sought to perform ex vivo 3D scanning of musculoskeletal oncology specimens to enhance communication between surgeons and pathologists. METHODS: Immediately after surgical resection, 3D scanning of the fresh specimen is performed prior to frozen section analysis. During pathologic grossing, whether frozen or permanent, margin sampling sites are annotated on the virtual 3D model using computer-aided design (CAD) software. RESULTS: 3D scanning was performed in seven cases (six soft tissue, one bone), with specimen mapping on six cases. Intraoperative 3D scanning and mapping was performed in one case in which the location of margin sampling was shown virtually in real-time to the operating surgeon to help achieve a negative margin. In six cases, the 3D model was used to communicate final permanent section analysis. Soft tissue, cartilage, and bone (including lytic lesions within bone) showed acceptable resolution. CONCLUSIONS: Virtual 3D scanning and specimen mapping is feasible and may allow for enhanced documentation and communication. This protocol provides useful information for anatomically complex musculoskeletal tumor specimens. Future studies will evaluate the effect of the protocol on positive margin rates, likelihood that a re-resection contains additional malignancy, and exploration of targeted adjuvant radiation protocols using a patient-specific 3D specimen map.

Utility of iliac crest tetracycline-labelled bone biopsy in osteoporosis and metabolic bone disease: An evaluation of 95 cases over a period of 25 years.

Background: Metabolic bone diseases (MBD) are typically diagnosed by non-invasive imaging and clinical biomarkers. However, imaging does not provide structural information, and biomarkers can be transiently affected by many systemic factors. Bone biopsy and pathologic evaluation is the gold standard for diagnosis of MBD, however, it is rarely utilized. We describe our technique for iliac crest tetracycline-labelled bone using a cannulated drill and assess the utility of bone biopsies to provide diagnostic and therapeutic guidance. Methods: In the 25-year period between March 1998 and January 2023, a total of 95 bone biopsies were performed on 94 patients for an osteological indication at Vanderbilt University Medical Center (VUMC). Patient demographics, bone biopsy indications, complications, diagnostic utility, and subsequent therapeutic guidance were retrospectively reviewed and analyzed. Results: The procedure had minimal complications and was well tolerated by patients. This technique provided good quality specimens for pathology, which helped establish a diagnosis and treatment change in most patients. Patients that had biopsy-guided treatment alterations showed significant increases in Dual-Energy X-ray Absorptiometry (DEXA) bone mineral density (BMD) scores post-biopsy and subsequent treatment. Conclusion: Despite scientific and technological progress in non-invasive diagnostic imaging, clinical biomarkers, and procedures for MBD, there remains a small but significant subset of patients who may benefit from inclusion of tetracycline-labelled bone biopsy into the diagnostic and therapeutic picture. Future prospective comparison studies are warranted. Mini abstract: Tetracycline-labelled bone biopsies are under-utilized. Biopsy led to a histological diagnosis and ensuing treatment alteration in most patients with significant increases in bone mineral density. The biopsy procedure used herein provided good specimens with low pain/adverse events. Bone biopsy remains a valuable tool in a small, though significant, subset of patients.

Accuracy of Time to Treatment Initiation Data in Musculoskeletal Soft Tissue Sarcoma.

Background: Time to treatment initiation (TTI) is a quality metric in cancer care. The purpose of this study is to determine the accuracy of TTI data from a single cancer center registry that reports to the National Cancer Database (NCDB) for sarcoma diagnoses. Methods: A retrospective analysis of a single Commission on Cancer (CoC)-accredited cancer center's tumor registry between 2006 and 2016 identified 402 patients who underwent treatment of a musculoskeletal soft tissue sarcoma and had TTI data available. Registry-reported TTI was extracted from the tumor registry. Effective TTI was manually calculated by medical record review as the number of days from the date of tissue diagnosis to initiation of first effective treatment. Effective treatment was defined as oncologic surgical excision or initiation of radiation therapy or chemotherapy. Registry-reported TTI and effective TTI values were compared for concordance in all patients. Results: In the entire cohort, 25% (99/402) of patients had TTI data discordance, all related to surgical treatment definition. For patients with a registry-reported value of TTI = 0 days, 74% (87/118) had a diagnostic surgical procedure coded as their first treatment event, with 73 unplanned incomplete excision procedures and 14 incisional biopsies. In these patients, effective TTI was on average 59 days (P < 0.001). For patients with a registry-reported value of TTI >0 days, only 4% (12/284) had discordant TTI values. Conclusions: Nearly three-fourths of patients with a registry-reported value of TTI = 0 days in a large, CoC-accredited cancer center registry had a diagnostic procedure coded as their first treatment event, though their effective treatment had not yet started. These data suggest that TTI is likely longer than what is reported to the NCDB. Redefinition of what constitutes surgical treatment should be considered to improve the accuracy of data used in measuring TTI in sarcoma.

Surgical Fixation Method in Lower Extremity Intercalary Allograft Reconstruction After Oncologic Resection: A Comparison of Plates and Nails.

INTRODUCTION: Fixation in intercalary allograft reconstruction includes plates and intramedullary nails. The purpose of this study was to examine rates of nonunion, fracture, the overall need for revision surgery, and allograft survival based on the surgical fixation method in lower extremity intercalary allografts. METHODS: A retrospective chart review was performed on 51 patients with intercalary allograft reconstruction in the lower extremity. Fixation methods compared were intramedullary fixation with nails (IMN) and extramedullary fixation with plates (EMP). Complications compared were nonunion, fracture, and wound complications. The alpha was set at 0.05 for statistical analysis. RESULTS: Nonunion incidence at all allograft-to-native bone junction sites was 21% (IMN) and 25% (EMP) ( P = 0.8). Fracture incidence was 24% (IMN) and 32% (EMP) ( P = 0.75). Median fracture-free allograft survival was 7.9 years (IMN) and 3.2 years (EMP) ( P = 0.04). Infection was seen in 18% (IMN) and 12% (EMP) ( P = 0.7). The overall need for revision surgery was 59% (IMN) and 71% (EMP) ( P = 0.53). Allograft survival at the final follow-up was 82% (IMN) and 65% (EMP) ( P = 0.33). When the EMP group was subdivided into single plate (SP) and multiple plate (MP) groups and compared with the IMN groups, fracture rates were 24% (IMN), 8% (SP), and 48% (MP) ( P = 0.04). Rates of revision surgery were 59% (IMN), 46% (SP), and 86% (MP) ( P = 0.04). Allograft survival at the final follow-up was 88% (IMN), 92% (SP), and 52% (MP) ( P = 0.05). DISCUSSION: Median fracture-free allograft survival was notably longer for the IMN group than the EMP group; otherwise, there were no notable differences between the intramedullary and extramedullary groups. When the EMP group was subdivided into the SP and MP groups, patients with MPs had higher rates of fracture, higher rates of revision surgery, and lower overall allograft survival. LEVEL OF EVIDENCE: III, Therapeutic Study, Retrospective Comparative Study.

Chronic Recurrent Multifocal Osteomyelitis: A Review of the Noninfectious Inflammatory Bone Disease and Lessons for More Timely Diagnosis.

Chronic recurrent multifocal osteomyelitis (CRMO) is an idiopathic autoinflammatory disease of the bone that typically occurs in children and adolescents. CRMO is characterized by recurrent periods of exacerbation and remission of symptomatic, osteolytic/sclerotic sterile bone lesions and is often a diagnosis of exclusion. Treatment consists of multimodal anti-inflammatory medication management by rheumatology and rarely involves surgery. This review summarizes the clinical presentation, pathophysiology, diagnosis, and management of this disease and highlights the role of the orthopedic surgeon. With increased familiarity with CRMO, clinicians will be able to diagnose and treat the condition in a more timely manner. [Orthopedics. 2023;46(3):e149-e155.].

Is the Number of National Database Research Studies in Musculoskeletal Sarcoma Increasing, and Are These Studies Reliable?

BACKGROUND: Large national databases have become a common source of information on patterns of cancer care in the United States, particularly for low-incidence diseases such as sarcoma. Although aggregating information from many hospitals can achieve statistical power, this may come at a cost when complex variables must be abstracted from the medical record. There is a current lack of understanding of the frequency of use of the Surveillance, Epidemiology, and End Results (SEER) database and the National Cancer Database (NCDB) over the last two decades in musculoskeletal sarcoma research and whether their use tends to produce papers with conflicting findings. QUESTIONS/PURPOSES: (1) Is the number of published studies using the SEER and NCDB databases in musculoskeletal sarcoma research increasing over time? (2) What are the author, journal, and content characteristics of these studies? (3) Do studies using the SEER and the NCDB databases for similar diagnoses and study questions report concordant or discordant key findings? (4) Are the administrative data reported by our institution to the SEER and the NCDB databases concordant with the data in our longitudinally maintained, physician-run orthopaedic oncology dataset? METHODS: To answer our first three questions, PubMed was searched from 2001 through 2020 for all studies using the SEER or the NCDB databases to evaluate sarcoma. Studies were excluded from the review if they did not use these databases or studied anatomic locations other than the extremities, nonretroperitoneal pelvis, trunk, chest wall, or spine. To answer our first question, the number of SEER and NCDB studies were counted by year. The publication rate over the 20-year span was assessed with simple linear regression modeling. The difference in the mean number of studies between 5-year intervals (2001-2005, 2006-2010, 2011-2015, 2016-2020) was also assessed with Student t-tests. To answer our second question, we recorded and summarized descriptive data regarding author, journal, and content for these studies. To answer our third question, we grouped all studies by diagnosis, and then identified studies that shared the same diagnosis and a similar major study question with at least one other study. We then categorized study questions (and their associated studies) as having concordant findings, discordant findings, or mixed findings. Proportions of studies with concordant, discordant, or mixed findings were compared. To answer our fourth question, a coding audit was performed assessing the concordance of nationally reported administrative data from our institution with data from our longitudinally maintained, physician-run orthopaedic oncology dataset in a series of patients during the past 3 years. Our orthopaedic oncology dataset is maintained on a weekly basis by the senior author who manually records data directly from the medical record and sarcoma tumor board consensus notes; this dataset served as the gold standard for data comparison. We compared date of birth, surgery date, margin status, tumor size, clinical stage, and adjuvant treatment. RESULTS: The number of musculoskeletal sarcoma studies using the SEER and the NCDB databases has steadily increased over time in a linear regression model (ß = 2.51; p < 0.001). The mean number of studies per year more than tripled during 2016-2020 compared with 2011-2015 (39 versus 13 studies; mean difference 26 ± 11; p = 0.03). Of the 299 studies in total, 56% (168 of 299) have been published since 2018. Nineteen institutions published more than five studies, and the most studies from one institution was 13. Orthopaedic surgeons authored 35% (104 of 299) of studies, and medical oncology journals published 44% (130 of 299). Of the 94 studies (31% of total [94 of 299]) that shared a major study question with at least one other study, 35% (33 of 94) reported discordant key findings, 29% (27 of 94) reported mixed key findings, and 44% (41 of 94) reported concordant key findings. Both concordant and discordant groups included papers on prognostic factors, demographic factors, and treatment strategies. When we compared nationally reported administrative data from our institution with our orthopaedic oncology dataset, we found clinically important discrepancies in adjuvant treatment (19% [15 of 77]), tumor size (21% [16 of 77]), surgery date (23% [18 of 77]), surgical margins (38% [29 of 77]), and clinical stage (77% [59 of 77]). CONCLUSION: Appropriate use of databases in musculoskeletal cancer research is essential to promote clear interpretation of findings, as almost two-thirds of studies we evaluated that asked similar study questions produced discordant or mixed key findings. Readers should be mindful of the differences in what each database seeks to convey because asking the same questions of different databases may result in different answers depending on what information each database captures. Likewise, differences in how studies determine which patients to include or exclude, how they handle missing data, and what they choose to emphasize may result in different messages getting drawn from large-database studies. Still, given the rarity and heterogeneity of sarcomas, these databases remain particularly useful in musculoskeletal cancer research for nationwide incidence estimations, risk factor/prognostic factor assessment, patient demographic and hospital-level variable assessment, patterns of care over time, and hypothesis generation for future prospective studies. LEVEL OF EVIDENCE: Level III, therapeutic study.

Adjuvant Radiation after Primary Resection of Atypical Lipomatous Tumors of the Extremity Reduces Local Recurrence but Increases Complications: A Multicenter Evaluation.

Background: Radiation after resection of an atypical lipomatous tumor (ALT) is controversial. This study evaluates local control and complications after the first resection of ALTs of the extremity with or without adjuvant radiation. Methods: A dual institution, retrospective review of patients treated from 1995 to 2020 with first-time resection of an ALT in the extremity was performed. In total, 102 patients underwent adjuvant radiation (XRT group) and 68 patients were treated with surgery alone (no-XRT group). The median follow-up time was 4.6 years (interquartile range (IQR) 2.0-7.3 years). The median radiation dose was 60 Gy (IQR 55-66 Gy). Univariable and multivariable analyses evaluated the association of patient, tumor, and treatment variables with recurrence and complications. Kaplan-Meier analysis evaluated local recurrence-free survival (LRFS) and time to complication. Results: The overall incidence of local recurrence was 1% (1/102) in the XRT group and 24% (16/68) in the no-XRT group (p < 0.001). The median time-to-recurrence was 8.2 years (IQR 6.5-10.5 years). In the XRT and the no-XRT groups, 5-yr LRFS was 98% and 92% (p=0.21) and 10-yr LRFS was 98% and 41% (p < 0.001), respectively. The absence of radiation (HR = 23.63, 95% CI (3.09-180.48); p < 0.001) and R2 surgical resection margins (HR = 11.04, 95% CI (2.07-59.03); p < 0.001) incurred a 23-fold and 11-fold increased risk of local recurrence, respectively, while tumor size, depth, location, and neurovascular involvement were not found to be independent predictors of recurrence. The complication rate was 37% (38/102) in the XRT group and 10% (7/68) in the no-XRT group (p < 0.001). Eight patients (8/102, 8%) required surgical management for complication in the XRT group compared with two patients (2/68, 3%) in the no-XRT group (p=0.10). Higher radiation dose had a modest correlation with increased severity of complication (ρ=0.24; p=0.02). Conclusions: Adjuvant radiation after first-time resection of an ALT of the extremity was associated with a significantly reduced risk of local recurrence but a three-fold increase in complication rate. These data support a 10-year follow-up for these patients and inform a notable clinical trade-off if considering adjuvant radiation for this tumor with recurrent potential.

Multicenter, retrospective comparison of implant survival, complications and cost between plate and screw and intramedullary nail fixation for metastatic lesions of the diaphyseal humerus.

Background: The humerus is a common site of metastatic disease that can be fixated with either plate and screw or intramedullary nail (IMN) constructs. A multicenter retrospective comparison study was undertaken to compare implant survival, complication rate and cost between the two constructs. No prior studies have included a cost comparison. Methods: Databases of two academic practices were queried retrospectively to identify patients with metastases of the humerus. Inclusion criteria were a lesion in the proximal metaphysis to distal diaphysis and amenable to both implant options with available cost data. Follow-up was at least 6 months barring death or discharge to hospice sooner. Demographic, clinical and outcome data was recorded. Costs were estimated based on contract pricing. Operating room (OR) costs were estimated using per minute OR costs proposed by other investigators. Results: One hundred and one humeri in 96 patients were included (72 plates and 29 nails). The most common malignancies were renal cell, myeloma and lung. Half presented with a displaced fracture. Demographics were similar in both groups. Lesions were larger in the plate group. Surgical times were longer in the plate group, 146 vs. 75 min, P<0.001. Estimated blood loss (EBL) was higher in the plate group, 510 vs. 221 mL, P<0.001. A trend toward increased failure was seen in the plate group, 12.5% vs. 0% (P=0.056). The most common complications in the plate group were pain, stiffness and swelling compared to pain, refracture and PE in the nail group. Local disease progression was equivalent. Implant costs were higher in the IMN group ($2,753 vs. $1,553, P<0.001), while OR costs were lower ($2,349 vs. $4,395, P<0.001). Overall cost of implantation was lower in the IMN group ($5,102 vs. $5,949, P=0.005). Conclusions: IMN of metastases of the humerus offers a faster, potentially more durable construct with lower blood loss, faster OR times and decreased cost of implantation.

Telemedicine in Orthopedic Oncology During COVID-19: Patient Satisfaction, Reimbursement, and Physical Examination Competency.

The coronavirus disease 2019 (COVID-19) pandemic forced many institutions to implement telemedicine to facilitate continued patient care at a distance. The quality of patient care with telemedicine in orthopedic oncology has not been assessed. Between March and June 2020, a telephone survey of 64 patients was conducted in an academic orthopedic oncology practice. Patient satisfaction was assessed with a Likert scale metric, open-ended feedback, and direct comparisons between telemedicine and in-office visits. Billing and collection financial data of the telemedicine cohort and of a separate cohort of in-office visits during the same time period were compared. The clinical competency of telemedicine visits was measured by delayed or missed diagnoses and surgical site infections that may be attributable to lack of an in-person physical examination. Overall, patients were largely satisfied with their telemedicine experience. More than 90% of patients described telemedicine as equal to or better than in-office visits regarding convenience, time, privacy, and overall quality. Patients reported that better assessment of their physical condition may be indicated, particularly in early postoperative and early sarcoma surveillance visits. Two of 64 patients had adverse events (both local recurrences) potentially attributable to lack of an in-person physical examination. Institutional financial reimbursement of telemedicine visits was comparable to that of in-office visits. These findings have supported continued use of telemedicine in our practice, particularly for patients traveling significant distance and those returning for sarcoma surveillance. However, the limitations of lack of an in-person physical examination should be considered on a case-by-case basis. [Orthopedics. 2021;44(5):274-279.].

Inadvertent Inguinal Sarcoma Excision during Hernia Surgery: Outcomes, Gender Analysis, and Prevention.

INTRODUCTION: Inadvertent excision of a soft tissue sarcoma during hernia surgery is a preventable clinical scenario that leads to unnecessary patient morbidity. Prior series are few, which only include male patients with little focus on prevention. The purpose of this study is to report the presenting features and outcomes of both male and female patients who underwent inadvertent inguinal sarcoma excision during hernia surgery. METHODS: A retrospective analysis of a single sarcoma referral center identified 33 patients who were referred for definitive treatment. Patients were divided into three clinically relevant groups based on intraoperative diagnosis, sex, and location of the mass relative to the inguinal ligament. T-tests and Fisher's exact tests were performed to compare continuous and categorical variables, respectively. Kaplan-Meier modeling was performed to assess sarcoma-specific survival. RESULTS: Females were younger (47 years vs. 61 years, p=0.003) and had smaller sarcomas (6.7 cm vs. 11 cm, p=0.012) compared to males. Only two sarcomas (2/33, 6%) were <4 cm in size. The majority of sarcomas in females were above the inguinal ligament (12/14, 86%). Twenty-nine (88%) underwent definitive R0 excision. The mean number of surgeries per patient was three (range 1-13), with nineteen (58%) patients requiring flap reconstruction and six (18%) requiring vascular bypass. Five patients locally recurred (15%) at a mean of 38 months after definitive excision (range 5-128 months). Overall sarcoma-specific disease-free survival was 64%, with no difference between males (80 ± 11%) and females (59 ± 17%) (p=0.885). Mean follow-up was 75 months (range 5-212). CONCLUSION: This is the second largest study regarding inadvertent inguinal sarcoma excision and the first to include females. When a suspected hernia is >4 cm, irreducible, firm, and is growing, especially in females, consider obtaining preoperative advanced three-dimensional imaging (CT or MRI) that can differentiate a neoplasm from a hernia.

The Size of Intramedullary Fixation Affects Endochondral-Mediated Angiogenesis During Fracture Repair.

OBJECTIVES: To explore the effect of intramedullary pin size on the biology of a healing fracture, specifically endochondral angiogenesis. We hypothesized that fracture fixation with a smaller pin would permit greater interfragmentary strain resulting in increased total amount of vascular endothelial growth factor within the callus and greater angiogenesis compared to fixation with a larger pin. METHODS: Transverse mid-shaft femur fractures in 8-week-old mice were fixed with either a 23-gauge (G) or 30-G pin. Differences in interfragmentary strain at the fracture site were estimated between cohorts. A combination of histology, gene expression, serial radiography, and microcomputed tomography with and without vascular contrast agent were used to assess fracture healing and vascularity for each cohort. RESULTS: Larger soft-tissue callus formation increased vascular endothelial growth factor-A expression, and a corresponding increase in vascular volume was observed in the higher strain, 30-G cohort. Radiographic analysis demonstrated earlier hard callus formation with greater initial interfragmentary strain, similar rates of union between pin size cohorts, yet delayed callus remodeling in mice with the larger pin size. CONCLUSIONS: These findings suggest that the stability conferred by an intramedullary nail influences endochondral angiogenesis at the fracture.

Trauma-Induced Nanohydroxyapatite Deposition in Skeletal Muscle is Sufficient to Drive Heterotopic Ossification.

Heterotopic ossification (HO), or the pathologic formation of bone within soft tissues, is a significant complication following severe injuries as it impairs joint motion and function leading to loss of the ability to perform activities of daily living and pain. While soft tissue injury is a prerequisite of developing HO, the exact molecular pathology leading to trauma-induced HO remains unknown. Through prior investigations aimed at identifying the causative factors of HO, it has been suggested that additional predisposing factors that favor ossification within the injured soft tissues environment are required. Considering that chondrocytes and osteoblasts initiate physiologic bone formation by depositing nanohydroxyapatite crystal into their extracellular environment, we investigated the hypothesis that deposition of nanohydroxyapatite within damaged skeletal muscle is likewise sufficient to predispose skeletal muscle to HO. Using a murine model genetically predisposed to nanohydroxyapatite deposition (ABCC6-deficient mice), we observed that following a focal muscle injury, nanohydroxyapatite was robustly deposited in a gene-dependent manner, yet resolved via macrophage-mediated regression over 28 days post injury. However, if macrophage-mediated regression was inhibited, we observed persistent nanohydroxyapatite that was sufficient to drive the formation of HO in 4/5 mice examined. Together, these results revealed a new paradigm by suggesting the persistent nanohydroxyapatite, referred to clinically as dystrophic calcification, and HO may be stages of a pathologic continuum, and not discrete events. As such, if confirmed clinically, these findings support the use of early therapeutic interventions aimed at preventing nanohydroxyapatite as a strategy to evade HO formation.

Unexpected timely fracture union in matrix metalloproteinase 9 deficient mice.

Immediately following a fracture, a fibrin laden hematoma is formed to prevent bleeding and infection. Subsequently, the organized removal of fibrin, via the protease plasmin, is essential to permit fracture repair through angiogenesis and ossification. Yet, when plasmin activity is lost, the depletion of fibrin alone is insufficient to fully restore fracture repair, suggesting the existence of additional plasmin targets important for fracture repair. Previously, activated matrix metalloproteinase 9 (MMP-9) was demonstrated to function in fracture repair by promoting angiogenesis. Given that MMP-9 is a defined plasmin target, it was hypothesized that pro-MMP-9, following plasmin activation, promotes fracture repair. This hypothesis was tested in a fixed murine femur fracture model with serial assessment of fracture healing. Contrary to previous findings, a complete loss of MMP-9 failed to affect fracture healing and union through 28 days post injury. Therefore, these results demonstrated that MMP-9 is dispensable for timely fracture union and cartilage transition to bone in fixed femur fractures. Pro-MMP-9 is therefore not a significant target of plasmin in fracture repair and future studies assessing additional plasmin targets associated with angiogenesis are warranted.

Surgical Outcomes After Limb-Sparing Resection and Reconstruction for Pelvic Sarcoma: A Systematic Review.

BACKGROUND: Limb-sparing resection and reconstruction for pelvic sarcomas in multiple small studies have been fraught with complications, reoperations, and impaired patient function. However, the non-oncologic complication and reoperation rates and functional outcomes for patients have never been rigorously compiled, to our knowledge. A systematic review was undertaken to more accurately determine the non-oncologic complication and reoperation rates and functional outcomes for patients after pelvic sarcoma resection and reconstruction. METHODS: The review was performed in accordance with PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines. PubMed and Cochrane database searches of English-only studies using the terms "pelvis AND sarcoma" and "pelvis AND sarcoma AND surgery" were performed. Study inclusion criteria were ≥10 patients enrolled, at least 12 months of follow-up, utilization of comparable functional outcome measure(s), and the majority of the resections treating primary bone sarcoma. RESULTS: In this study, 2,350 studies were reviewed, of which 22 Level-IV studies with a total of 801 patients met inclusion criteria. Reconstructive techniques varied widely and included allografts, allograft-prosthesis composites, saddle prostheses, custom endoprostheses, and irradiated autografts. Pooled means showed a mean 5-year patient survival of 55%. The mean non-oncologic complication rate was 49%. The mean non-oncologic reoperation rate was 37%. The mean Musculoskeletal Tumor Society score was 65%. CONCLUSIONS: The non-oncologic complication and reoperation rates for pelvic reconstructions are remarkably high and 5-year survival is poor. Functional outcomes are acceptable but may not be better than a resection of the same Enneking and Dunham type without reconstruction. Consideration should be given to forgoing pelvic reconstruction, especially in patients with poor overall prognosis. Further studies comparing non-oncologic complication rates, reoperation rates, and functional outcomes in patients with equivalent resections treated with or without reconstruction are needed to further elucidate the utility of pelvic reconstruction. LEVEL OF EVIDENCE: Therapeutic Level IV. See Instructions for Authors for a complete description of levels of evidence.

Development of a modular fluorescence overlay tissue imaging system for wide-field intraoperative surgical guidance.

Fluorescence imaging is a well-established optical modality that has been used to localize and track fluorophores in vivo and has demonstrated great potential for surgical guidance. Despite the variety of fluorophores currently being researched, many existing intraoperative fluorescence imaging systems are specifically designed for a limited number of applications. We present a modular wide-field fluorescence overlay tissue imaging system for intraoperative surgical guidance that is comprised of commercially available standardized components. Its modular layout allows for the accommodation of a broad range of fluorophores, fields of view (FOV), and spatial resolutions while maintaining an integrated portable design for intraoperative use. Measurements are automatic and feature a real-time projection overlay technique that intuitively displays fluorescence maps directly onto a [Formula: see text] FOV from a working distance of 35 cm. At a 20-ms exposure time, [Formula: see text] samples of indocyanine green could be measured with high signal-to-noise ratio and was later tested in an in vivo mouse model before finally being demonstrated for intraoperative autofluorescence imaging of human soft tissue sarcoma margins. The system's modular design and ability to enable naked-eye visualization of wide-field fluorescence allow for the flexibility to adapt to numerous clinical applications and can potentially extend the adoption of fluorescence imaging for intraoperative use.

Autologous chondrocyte grafting promotes bone formation in the posterolateral spine.

BACKGROUND CONTEXT: Pseudarthrosis following spinal fusion remains problematic despite modern surgical and grafting techniques. In surgical spinal fusion, new bone forms via intramembranous and endochondral ossification, with endochondral ossification occurring in the hypoxic zones of the fusion bed. During bone development and fracture healing, the key cellular mediator of endochondral ossification is the hypertrophic chondrocyte given its ability to function in hypoxia and induce neovascularization and ossification. We therefore hypothesize that hypertrophic chondrocytes may be an effective bone graft alternative. PURPOSE: Spinal fusion procedures have increased substantially; yet 5% to 35% of all spinal fusions may result in pseudoarthrosis. Pseudoarthrosis may occur because of implant failure, infection, or biological failure, among other reasons. Advances in surgical techniques and bone grafting have improved fusion; however pseudarthrosis rates remain unacceptably high. Thus, the goal of this study is to investigate hypertrophic chondrocytes as a potential biological graft alternative. METHODS: Using a validated murine fracture model, hypertrophic chondrocytes were harvested from fracture calluses and transplanted into the posterolateral spines of identical mice. New bone formation was assessed by X-ray, microcomputed tomography (µCT), and in vivo fluorescent imaging. Results were compared against a standard iliac crest bone graft and a sham surgery control group. Funding for this work was provided by the Department of Orthopaedics and Rehabilitation, the OREF (Grant #16-150), and The Caitlin Lovejoy Fund. RESULTS: Radiography, µCT, and in vivo fluorescent imaging demonstrated that hypertrophic chondrocytes promoted bone formation at rates equivalent to iliac crest autograft. Additionally, µCT analysis demonstrated similar fusion rates in a subset of mice from the iliac crest and hypertrophic chondrocyte groups. CONCLUSIONS: This proof-of-concept study indicates that hypertrophic chondrocytes can promote bone formation comparable to iliac crest bone graft. These findings provide the foundation for future studies to investigate the potential therapeutic use of hypertrophic chondrocytes in spinal fusion.

Cost-utility of osteoarticular allograft versus endoprosthetic reconstruction for primary bone sarcoma of the knee: A markov analysis.

BACKGROUND: The most cost-effective reconstruction after resection of bone sarcoma is unknown. The goal of this study was to compare the cost effectiveness of osteoarticular allograft to endoprosthetic reconstruction of the proximal tibia or distal femur. METHODS: A Markov model was used. Revision and complication rates were taken from existing studies. Costs were based on Medicare reimbursement rates and implant prices. Health-state utilities were derived from the Health Utilities Index 3 survey with additional assumptions. Incremental cost-effectiveness ratios (ICER) were used with less than $100 000 per quality-adjusted life year (QALY) considered cost-effective. Sensitivity analyses were performed for comparison over a range of costs, utilities, complication rates, and revisions rates. RESULTS: Osteoarticular allografts, and a 30% price-discounted endoprosthesis were cost-effective with ICERs of $92.59 and $6 114.77. One-way sensitivity analysis revealed discounted endoprostheses were favored if allografts cost over $21 900 or endoprostheses cost less than $51 900. Allograft reconstruction was favored over discounted endoprosthetic reconstruction if the allograft complication rate was less than 1.3%. Allografts were more cost-effective than full-price endoprostheses. CONCLUSIONS: Osteoarticular allografts and price-discounted endoprosthetic reconstructions are cost-effective. Sensitivity analysis, using plausible complication and revision rates, favored the use of discounted endoprostheses over allografts. Allografts are more cost-effective than full-price endoprostheses.

Plasmin Prevents Dystrophic Calcification After Muscle Injury.

Extensive or persistent calcium phosphate deposition within soft tissues after severe traumatic injury or major orthopedic surgery can result in pain and loss of joint function. The pathophysiology of soft tissue calcification, including dystrophic calcification and heterotopic ossification (HO), is poorly understood; consequently, current treatments are suboptimal. Here, we show that plasmin protease activity prevents dystrophic calcification within injured skeletal muscle independent of its canonical fibrinolytic function. After muscle injury, dystrophic calcifications either can be resorbed during the process of tissue healing, persist, or become organized into mature bone (HO). Without sufficient plasmin activity, dystrophic calcifications persist after muscle injury and are sufficient to induce HO. Downregulating the primary inhibitor of plasmin (α2-antiplasmin) or treating with pyrophosphate analogues prevents dystrophic calcification and subsequent HO in vivo. Because plasmin also supports bone homeostasis and fracture repair, increasing plasmin activity represents the first pharmacologic strategy to prevent soft tissue calcification without adversely affecting systemic bone physiology or concurrent muscle and bone regeneration. © 2016 American Society for Bone and Mineral Research.