Effectiveness of immune checkpoint inhibitor therapy on bone metastases in non-small-cell lung cancer.

Background: Bone metastases (BoMs) are prevalent in patients with metastatic non-small-cell lung cancer (NSCLC) however, there are limited data detailing how BoMs respond to immune checkpoint inhibitors (ICIs). The purpose of this study was to compare the imaging response to ICIs of BoMs against visceral metastases and to evaluate the effect of BoMs on survival. Materials and methods: A retrospective, multicentre cohort study was conducted in patients with NSCLC treated with nivolumab or pembrolizumab in Alberta, Canada from 2015 to 2020. The primary endpoint was the real-world organ specific progression free survival (osPFS) of bone versus visceral metastases. Visceral metastases were categorized as adrenal, brain, liver, lung, lymph node, or other intra-abdominal lesions. The secondary outcome was overall survival (OS) amongst patients with and without BoMs. Results: A total of 573 patients were included of which all patients had visceral metastases and 243 patients (42.4%) had BoMs. High PD-L1 expression was identified in 268 patients (46.8%). No significant difference in osPFS was observed between bone, liver, and intra-abdominal metastases (p=0.20 and p=0.76, respectively), with all showing shorter osPFS than other disease sites. There was no difference in the osPFS of extra-thoracic sites of disease in patients with high PD-L1 expression. There was significant discordance between visceral disease response and bone disease response to ICI (p=0.047). The presence of BoMs was an independent poor prognostic factor for OS (HR 1.26, 95%CI: 1.05-1.53, p=0.01). Conclusion: Metastatic bone, liver, and intra-abdominal lesions demonstrated inferior clinical responses to ICI relative to other sites of disease. Additionally, the presence of bone and liver metastases were independent poor prognostic factors for overall survival. This real-world data suggests that BoMs respond poorly to ICI and may require treatment adjuncts for disease control.

Emerging innovations and advancements in the treatment of extremity and truncal soft tissue sarcomas.

In this special edition update on soft tissue sarcomas (STS), we cover classifications, emerging technologies, prognostic tools, radiation schemas, and treatment disparities in extremity and truncal STS. We discuss the importance of enhancing local control and reducing complications, including the role of innovative imaging, surgical guidance, and hypofractionated radiation. We review advancements in systemic and immunotherapeutic treatments and introduce disparities seen in this vulnerable population that must be considered to improve overall patient care.

What are the indications and survivorship of tumor endoprosthetic reconstructions for patients with extremity metastatic bone disease?

BACKGROUND AND OBJECTIVES: Given advances in therapies, endoprosthetic reconstruction (EPR) in metastatic bone disease (MBD) may be increasingly indicated. The objectives were to review the indications, and implant and patient survivorship in patients undergoing EPR for MBD. METHODS: A review of patients undergoing EPR for extremity MBD between 1992 and 2022 at two centers was performed. Surgical data, implant survival, patient survival, and implant failure modes were examined. RESULTS: One hundred fifteen patients were included with a median follow-up of 14.9 months (95% confidence interval [CI]: 9.2-19.3) and survival of 19.4 months (95% CI: 13.6-26.1). The most common diagnosis was renal cell carcinoma (34/115, 29.6%) and the most common location was proximal femur (43/115, 37.4%). Indications included: actualized fracture (58/115, 50.4%), impending fracture (30/115, 26.1%), and failed fixation (27/115, 23.5%). Implant failure was uncommon (10/115, 8.7%). Patients undergoing EPR for failed fixation were more likely to have renal or lung cancer (p = 0.006). CONCLUSIONS: EPRs were performed most frequently for renal cell carcinoma and in patients with a relatively favorable survival. EPR was indicated for failed previous fixation in 23.5% of cases, emphasizing the importance of predictive survival modeling. EPR can be a reliable and durable surgical option for patients with MBD.

Heightened Procoagulation after Post-Operative Thromboprophylaxis Completion in Patients with Metastatic Bone Disease from Primary Colorectal Cancer.

BACKGROUND: Platelets play a role in venous thromboembolism (VTE) and in mediating colorectal cancer (CRC) progression. Still, platelets' role in hypercoagulability after surgical intervention for metastatic bone disease (MBD) is ill-defined. METHODS: In this quantitative observational study, we utilized a high-resolution imaging approach to temporally examine platelet procoagulant membrane dynamics (PMD) in four patients with MBD from primary CRC (CRC/MBD), before and after surgical intervention, over a 6-month period. We coupled this investigation with thrombelastography, quantitative plasma shotgun proteomics, and biochemical analysis. RESULTS: The plasma of CRC/MBD patients was enriched in ADAM1a, ADAMTS7, and physiological ligands for platelet glycoprotein-VI/spleen tyrosine kinase (GPVI/Syk) activation. Thromboprophylaxis attenuated procoagulation upon its initial prescription (post-operative day one, POD1); however, all patients experienced rebound procoagulation between POD3 and POD14, which was associated with Syk activation (Y525/Y526) in all patients, and a VTE event in two patients. Plasma levels of DNA-histone complexes increased steadily after surgery and remained elevated throughout the study period. Additionally, we increasingly sighted both homotypic and heterotypic platelet microaggregates after surgery in CRC/MBD patients, but not in healthy control participants' plasma. CONCLUSIONS: Our data elucidates the cell biology of a prothrombo-inflammatory state caused by disease and vascular injury, and recalcitrant to thromboprophylaxis. New mechanistic insights into hypercoagulability in CRC/MBD patients may identify novel drug targets for effective thromboprophylaxis type and duration after orthopaedic surgery.

MDM2 analysis in the management of benign lipomas versus atypical lipomatous tumors/well-differentiated liposarcomas: A useful prognostication tool?

INTRODUCTION: Well-differentiated liposarcomas (WDLS) are low-grade lipomatous tumors with low malignant potential. Previous review identified controversy on whether upfront wide resection is necessary when they occur on the trunk or the extremities. MDM2 amplification is a genetic mutation typically present in WDLS and absent in benign lipomas (BL). We aimed to study the influence of MDM2 status on the management/recurrences of lipomatous tumors in the trunk or the extremities. METHODS: All patients with lipomatous tumors with MDM2 testing in the Province of Alberta between 2015 and 2020 were identified from the Cancer Cytogenetics Laboratory dataset. High grade sarcomas, retroperitoneal, head/neck, or groin tumors were excluded. Primary outcome measures including MDM2 status, surgical margin, local recurrence, reoperation rate, dedifferentiation, and metastasis were abstracted from chart review. Descriptive statistics were used to analyse treatment patterns and recurrence rates according to MDM2 status. RESULTS: Total of 764 charts were retrieved, and 282 were included for analysis. 33 showed MDM2 amplification (11.7%), and 2 of them had local recurrence (6.1%). Two patients with recurrent tumors underwent limb-salvaging reoperation (6.1%), but no dedifferentiation or metastasis was seen. CONCLUSION: Findings in this study confirmed the benign behaviour of truncal/extremities lipomas with no MDM2 amplification. Given we found a 6.1% recurrence rate in MDM2 amplified tumors, a prolong follow up of this subset of patients is warranted. Overall, regardless of the MDM2 status, we believe an initial marginal excision is a reasonable surgical approach as recurrences are rare, and they can be managed with re-excision when they occur.

Does surgical technique influence the burden of lung metastases in patients with pathologic long bone fractures?

BACKGROUND: The aims of this study are to (1) determine whether fixation of metastatic long bone fractures with an intramedullary nail (IMN) influences the incidence of lung metastasis in comparison to arthroplasty or ORIF (Arthro/ORIF); and (2) assess this relationship in primary tumor types; and (3) to assess survival implications of lung metastasis after surgery. METHODS: Retrospective cohort study investigating 184 patients (107 IMN, and 77 Arthro/ORIF) surgically treated for metastatic long bone fractures. Patients were required to have a single surgically treated impending or established pathologic fracture of a long bone, pre-operative lung imaging (lung radiograph or computed tomography) and post-operative lung imaging within 6 months of surgery. Primary cancer types included were breast (n = 70), lung (n = 43), prostate (n = 34), renal cell (n = 37). Statistical analyses were conducted using two-tailed Fisher's exact tests, and Kaplan-Meier survival analyses. RESULTS: Patients treated with IMN and Arthro/ORIF developed new or progressive lung metastases following surgery at an incidence of 34 and 26%, respectively. Surgical method did not significantly influence lung metastasis (p = 0.33). Furthermore, an analysis of primary cancer subgroups did not yield any differences between IMN vs Arthro/ORIF. Median survival for the entire cohort was 11 months and 1-year overall survival was 42.7% (95% CI: 35.4-49.8). Regardless of fixation method, the presence of new or progressive lung metastatic disease at follow up imaging study was found to have a negative impact on patient survival (p < 0.001). CONCLUSIONS: In this study, development or progression of metastatic lung disease was not affected by long bone stabilization strategy. IM manipulation of metastatic long bone fractures therefore may not result in a clinically relevant increase in metastatic lung burden. The results of this study also suggest that lung metastasis within 6 months of surgery for metastatic long bone lesions is negatively associated with patient survival. LEVEL OF EVIDENCE: III, therapeutic study.

What Are the Long-term Surgical Outcomes of Compressive Endoprosthetic Osseointegration of the Femur with a Minimum 10-year Follow-up Period?

BACKGROUND: Endoprosthetic reconstruction after oncologic resection of bone tumors requires stable fixation between the prosthesis and residual host bone. Compressive osseointegration has been developed as an alternative to traditional stemmed implants to address the challenges and complications of achieving this fixation. Sufficient time has now passed from the advent of compressive implants to allow for an assessment of the intermediate-term and long-term results of this form of fixation. QUESTIONS/PURPOSES: At a minimum follow-up of 10 years after implantation of a compressive osseointegration device for oncologic reconstruction: (1) What is the risk of periprosthetic fracture, aseptic loosening, or implant breakage resulting in revision surgery for endoprosthesis removal? (2) What is the long-term cortical response at the host-endoprosthesis interface as visualized on plain radiographs? METHODS: A single-center, retrospective study was performed between 2002 and 2010, in which 110 patients with primary bone sarcoma of the proximal or distal femur were considered for oncologic resection and reconstruction. Patients were considered for a compressive osseointegration endoprosthesis if they were 50 years of age or younger, had not previously received femoral radiation, had no metabolic disease impairing bone healing, were not diagnosed with metastatic disease, and had life expectancy greater than six months. Of the 110 patients, 25 were treated with a compressive osseointegration implant of the proximal or distal femur, and 85 patients were treated with conventional stemmed implants or amputation because of older age, advanced disease, metabolic comorbidities, inability to tolerate a nonweightbearing postoperative period, or in the case of rotationplasty, patient preference. All patients who received this device during the period of study were considered eligible for inclusion in this review. The median (range) age was 18 years (7 to 50), and 13 of 25 patients were men. Five patients died of disease before the minimum follow-up duration of 10 years; two underwent amputation due to local recurrence and three died with the implant in situ, leaving 20 patients for complete analysis. Median follow-up was 144 months, and all 20 surviving patients had a minimum follow-up of 10 years (121 to 230 months). The primary endpoint was reoperation and implant removal for periprosthetic fracture, aseptic loosening, or mechanical breakage of any component of the compressive device in the endoprosthesis. In final analysis, death was considered a competing event to revision surgery, and cumulative incidence was reported after competing-event analysis. A secondary aim was radiographic evaluation of the host-implant interface to assess the long-term cortical response to compressive osseointegration. RESULTS: Spindle fracture or loosening was noted in three patients, and the remaining 17 patients maintained the compression device until the final follow-up. The risk of reoperation for aseptic loosening, periprosthetic fracture, or mechanical breakage of the implant using a competing risks estimator was 12% at 10 years (95% CI 0% to 26%). These complications occurred within 29 months of the index surgery; no patients had implant loosening or mechanical breakdown after this initial period. On radiographic assessment, 14 patients demonstrated cortical hypertrophy of the bone-implant interface, six patients had maintenance of the native cortical contour, and no patients had cortical atrophy or narrowing at the implant interface.Conclusion Long-term follow-up in patients with compressive osseointegrative endoprosthetic devices demonstrated no late revisions because of periprosthetic fracture, aseptic loosening, or implant breakage in this cohort with a minimum 10-year follow-up. There was no evidence of late-onset cortical atrophy or stress shielding at the host-implant interface. This study supports the long-term stability of the interface between host bone and the endoprosthesis in compressive osseointegration devices. LEVEL OF EVIDENCE: Level IV, therapeutic study.

Intratumoral STING activation causes durable immunogenic tumor eradication in the KP soft tissue sarcoma model.

Introduction: Soft tissue sarcomas (STS) are highly metastatic, connective-tissue lineage solid cancers. Immunologically, sarcomas are frequently characterized by a paucity of tumor infiltrating lymphocytes and an immune suppressive microenvironment. Activation of the STING pathway can induce potent immune-driven anti-tumor responses within immunogenic solid tumors; however, this strategy has not been evaluated in immunologically cold sarcomas. Herein, we assessed the therapeutic response of intratumoral STING activation in an immunologically cold murine model of undifferentiated pleomorphic sarcoma (UPS). Materials and Results: A single intratumoral injection of the murine STING agonist, DMXAA resulted in durable cure in up to 60% of UPS-bearing mice. In mice with synchronous lung metastases, STING activation within hindlimb tumors resulted in 50% cure in both anatomic sites. Surviving mice all rejected UPS re-challenge in the hindlimb and lung. Therapeutic efficacy of STING was inhibited by lymphocyte deficiency but unaffected by macrophage deficiency. Immune phenotyping demonstrated enrichment of lymphocytic responses in tumors at multiple timepoints following treatment. Immune checkpoint blockade enhanced survival following STING activation. Discussion: These data suggest intratumoral activation of the STING pathway elicits local and systemic anti-tumor immune responses in a lymphocyte poor sarcoma model and deserves further evaluation as an adjunctive local and systemic treatment for sarcomas.

Longitudinal survival trends of patients with cancer with surgically managed appendicular metastatic bone disease: systematic review.

BACKGROUND: Advances in systemic cancer therapies have improved survival for patients with metastatic carcinoma; however, it is unknown whether these advances have translated to improved survival for patients with appendicular metastatic bone disease (A-MBD) after orthopedic interventions. We conducted a study to evaluate the trend in overall survival for patients who underwent orthopedic surgery for A-MBD between 1968 and 2018. METHODS: A systematic search of Embase and Medline to identify studies published since 1968 evaluating patients treated with orthopedic surgery for A-MBD was conducted for a previously published scoping review. We used a meta-regression model to assess the longitudinal trends in 1-, 2- and 5-year overall survival between 1968 and 2018. The midpoint year of patient inclusion for each study was used for analysis. We categorized primary tumour types into a tumour severity score according to prognosis for a further meta-regression analysis. RESULTS: Of the 5747 studies identified, 103 were retained for analysis. Meta-regression analysis showed no significant effect of midpoint study year on survival across all time points. There was no effect of the weighted average of tumour severity scores for each study on 1-year survival over time. CONCLUSION: There was no significant improvement in overall survival between 1968 and 2018 for patients with A-MBD who underwent orthopedic surgery. Orthopedic intervention remains a poor prognostic variable for patients with MBD. This finding highlights the need for improved collection of prospective data in this population to identify patients with favourable survival outcomes who may benefit from personalized oncologic surgical interventions.

Thromboembolic complications after surgical fixation of bone metastases: A systematic review.

BACKGROUND: Patients undergoing a major orthopedic surgery for metastatic bone disease (MBD) are at high risk of developing venous thromboembolic (VTE) complications. Despite concerns, there is no consensus on the most effective strategy to prevent VTE in these patients. The purpose of this systematic review was to determine the VTE rate following the surgical management of MBD. METHODS: The databases MEDLINE, EMBASE, and CENTRAL were searched using keywords related to VTE and MBD requiring surgical management. Included studies reported VTE rates in patients with surgically managed MBD. Descriptive statistics and weighted mean totals were calculated. RESULTS: In total, 2082 abstracts were screened, and 29 studies were included. The overall VTE rate was 4.7%. Patients receiving surgery for impending pathologic fracture had a higher rate of VTE (5.6%) compared to patients with acute pathologic fractures (4.2%). Low-molecular-weight heparin was the most used chemoprophylaxis. CONCLUSIONS: Relative to other cancer and orthopedic patients, the VTE rate is extremely high in patients with MBD. The discordant recommendations of thromboprophylaxis, and absence of research in this distinct and more granular surgical oncology subgroup, underpins the challenges associated with developing guidelines to lessen the VTE risks in the MBD patient population.

The KrasG12D;Trp53fl/fl murine model of undifferentiated pleomorphic sarcoma is macrophage dense, lymphocyte poor, and resistant to immune checkpoint blockade.

Sarcomas are rare, difficult to treat, mesenchymal lineage tumours that affect children and adults. Immunologically-based therapies have improved outcomes for numerous adult cancers, however, these therapeutic strategies have been minimally effective in sarcoma so far. Clinically relevant, immunologically-competent, and transplantable pre-clinical sarcoma models are essential to advance sarcoma immunology research. Herein we show that Cre-mediated activation of KrasG12D, and deletion of Trp53, in the hindlimb muscles of C57Bl/6 mice results in the highly penetrant, rapid onset undifferentiated pleomorphic sarcomas (UPS), one of the most common human sarcoma subtypes. Cell lines derived from spontaneous UPS tumours can be reproducibly transplanted into the hindlimbs or lungs of naïve, immune competent syngeneic mice. Immunological characterization of both spontaneous and transplanted UPS tumours demonstrates an immunologically-'quiescent' microenvironment, characterized by a paucity of lymphocytes, limited spontaneous adaptive immune pathways, and dense macrophage infiltrates. Macrophages are the dominant immune population in both spontaneous and transplanted UPS tumours, although compared to spontaneous tumours, transplanted tumours demonstrate increased spontaneous lymphocytic infiltrates. The growth of transplanted UPS tumours is unaffected by host lymphocyte deficiency, and despite strong expression of PD-1 on tumour infiltrating lymphocytes, tumours are resistant to immunological checkpoint blockade. This spontaneous and transplantable immune competent UPS model will be an important experimental tool in the pre-clinical development and evaluation of novel immunotherapeutic approaches for immunologically cold soft tissue sarcomas.

Venous thromboembolism rates in patients with bone and soft tissue sarcoma of the extremities following surgical resection: A systematic review.

BACKGROUND: Patients undergoing an orthopedic surgery for bone or soft tissue sarcoma are at increased venous thromboembolism (VTE) risk. Unfortunately, there is a lack of thromboprophylaxis guidelines in this population. The purpose of this systematic review was to determine the soft tissue and bone sarcoma VTE rate and to explore the thromboprophylaxis regimens used. METHODS: The databases MEDLINE, EMBASE, and CENTRAL were queried using keywords related to VTE and long bone malignancy requiring surgical intervention to 2020. Included studied reported VTE rate in patients with surgically managed extremity sarcoma. Descriptive statistics and weighted mean totals were calculated. RESULTS: A total of 2082 studies were screened and 23 studies were included. The overall VTE rate was 2.9%, with a rate of 3.7% and 1.4% in patients with bone and soft tissue sarcomas, respectively. Low-molecular-weight heparin was the most commonly used chemoprophylaxis. CONCLUSIONS: There is a high VTE rate following sarcoma surgery. The VTE rate is higher in bone sarcoma surgery, which may be attributed to differences in surgery and postoperative recovery. There was no consensus on the duration or type of thromboprophylaxis used. Future research is needed to determine the most effective thromboprophylaxis regimen in patients with sarcoma and whether individualized thromboprophylaxis is required.

Communication in surgical decision-making while managing metastatic bone disease: matching patient expectations with surgical goals.

BACKGROUND: There is a paucity of research examining how surgical decision-making for metastatic bone disease (MBD) can be optimized to improve quality of life (QOL) and functional outcomes, while accurately aligning with patient goals and expectations. The objective of this study was to survey and interview patients with MBD and support persons (PS), physicians, and allied health care providers (HCP) with the goal of identifying (1) important surgical issues related to MBD management, (2) discordance in perioperative expectations, and (3) perceived measures of success in the surgical management of MBD. METHODS: Utilizing a custom survey developed by HCP and patients with MBD, participants were asked to (1) identify important issues related to MBD management, (2) rank perceived measures of success, and (3) answer open-ended questions pertaining to the management of MBD. RESULTS: From the survey, increased life expectancy, minimizing disease progression, removal of local tumour, timely surgery after diagnosis, increased length of hospitalization, and physiotherapy access were all identified as significant discordant goals between PS and physicians/HCP. Conversely, there was an agreement between physicians and HCP who considered improved QOL and functional outcomes as most important goals. Structured homogenous-group workshops identified the need for (1) improved discussions of prognosis, surgical options, expectations, timelines, and resources, (2) the use of a care team "quarterback", and (3) an increased use of multi-disciplinary treatment planning. CONCLUSIONS: We feel this data highlights the importance of improved communication and coordination in treating patients with MBD. Further research evaluating how surgical techniques influence survival and disease progression in MBD is highly relevant and important to patients.

Is Use of BMP-2 Associated with Tumor Growth and Osteoblastic Differentiation in Murine Models of Osteosarcoma?

BACKGROUND: The putative benefit of rhBMP-2 is in the setting of limb reconstruction using structural allografts, whether it be allograft-prosthetic composites, osteoarticular allografts, or intercalary segmental grafts. There are also potential advantages in augmenting osseointegration of uncemented endoprosthetics and in reducing infection. Recombinant human BMP-2 might mitigate nonunion in structural allograft augmented osteosarcoma limb salvage surgery; however, its use is limited because of concerns about the prooncogenic effects of the agent. QUESTIONS/PURPOSES: (1) To assess if BMP-2 signaling influences osteosarcoma cell line growth. (2) To characterize degree of osteosarcoma cell line osteoblastic differentiation in response to BMP-2. (3) To assess if BMP-2 signaling has a consistent effect on local or systemic tumor burden in various orthotopic murine models of osteosarcoma. METHODS: In this study, 143b, SaOS-2 and DLM8-M1 osteosarcoma cell lines were transfected with BMP-2 cDNA controlled by a constitutive promoter (experimental) or an empty vector (control) using a PiggyBac transposon system. Cellular proliferation was assessed using a quantitative MTT colorimetric assay. Osteoblastic differentiation was compared between control and experimental cell lines using quantitative real-time polymerase chain reaction of the osteoblastic markers connective tissue growth factor, Runx-2, Osterix, alkaline phosphatase and osteocalcin. Experimental and control cell lines were injected into the proximal tibia of either NOD-SCID (143b and SaOS-2 xenograft model), or C3H (DLM8-M1 syngeneic model) mice. Local tumor burden was quantitatively assessed using tumor volume caliper measurements and bioluminescence, and qualitatively assessed using post-mortem ex vivo microCT. Lung metastasis was qualitatively assessed by the presence of bioluminescence, and incidence was confirmed using histology. rhBMP-2 soaked absorbable collagen sponges (experimental) and sterile-H2O soaked absorbable collagen sponges (control) were implanted adjacent to 143b proximal tibial cell line injections to compare the effects of exogenous BMP-2 application with endogenous upregulation. RESULTS: Constitutive expression of BMP-2 increased the in vitro proliferation of 143b cells (absorbance values 1.2 ± 0.1 versus 0.89 ± 0.1, mean difference 0.36 [95% CI 0.12 to 0.6]; p = 0.01), but had no effect on SaOS-2 and DLM8-M1 cell proliferation. In response to constitutive BMP-2 expression, 143b cells had no differences in osteoblastic differentiation, while DLM8-M1 cells downregulated the early marker connective tissue growth factor (mean ΔCt 0.2 ± 0.1 versus 0.6 ± 0.1; p = 0.002) and upregulated the early-mid range marker Runx-2 (mean ΔCt -0.8 ± 0.1 versus -1.1 ± 0.1; p = 0.002), and SaOS-2 cells upregulated the mid-range marker Osterix (mean ΔCt -2.1 ± 0.6 versus -3.9 ± 0.6; p = 0.002). Constitutive expression of BMP-2 resulted in greater 143b and DLM8-M1 local tumor volume (143b: 307.2 ± 106.8 mm versus 1316 ± 387.4 mm, mean difference 1009 mm [95% CI 674.5 to 1343]; p < 0.001, DLM8-M1 week four: 0 mm versus 326.1 ± 72.8 mm, mean difference 326.1 mm [95% CI 121.2 to 531]; p = 0.009), but modestly reduced local tumor growth in SaOS-2 (9.5 x 10 ± 8.3x10 photons/s versus 9.3 x 10 ± 1.5 x 10 photons/s, mean difference 8.6 x 10 photons/s [95% CI 5.1 x 10 to 1.2 x 10]; p < 0.001). Application of exogenous rhBMP-2 also increased 143b local tumor volume (495 ± 91.9 mm versus 1335 ± 102.7 mm, mean difference 840.3 mm [95% CI 671.7 to 1009]; p < 0.001). Incidence of lung metastases was not different between experimental or control groups for all experimental conditions. CONCLUSIONS: As demonstrated by others, ectopic BMP-2 signaling has unpredictable effects on local tumor proliferation in murine models of osteosarcoma and does not consistently result in osteosarcoma cell line differentiation. Further investigations into other methods of safe bone and soft tissue healing augmentation and the use of differentiation therapies is warranted. CLINICAL RELEVANCE: Our results indicate that BMP-2 has the potential to stimulate the growth of osteosarcoma cells that are poorly responsive to BMP-2 mediated osteoblastic differentiation. As this differentiation potential is unpredictable in the clinical setting, BMP-2 may promote the growth of microscopic residual tumor burden after resection. Our study provides further support for the recommendation to avoid the use of BMP-2 after limb-salvage surgery in patients with osteosarcoma.

Proximal Hamstring Tendon Avulsion Resulting in Acute Posterior Thigh Compartment Syndrome: A Case Report.

CASE: A healthy 36-year-old man developed compartment syndrome of the posterior thigh with an associated sciatic nerve palsy secondary to an acute proximal hamstring tendon avulsion injury. CONCLUSION: Compartment syndrome of the thigh is rare and is usually associated with high-energy trauma. Atraumatic causes have been described, typically involving the anterior compartment. Posterior thigh compartment syndrome is especially uncommon. This case highlights the potential occurrence of posterior thigh compartment syndrome after proximal hamstring tendon rupture. Given the morbidity associated with compartment syndrome, it is important to recognize the risk factors and injury patterns that can cause thigh compartment syndrome.

Intraoperative Near-infrared Spectroscopy Correlates with Skin Flap Necrosis: A Prospective Cohort Study.

BACKGROUND: Skin flap necrosis (SFN) is a morbid complication that is disfiguring, leads to acute and chronic wound issues, often requires further surgery, and can delay adjuvant chemotherapy. Although most surgeons rely on the clinical examination, near-infrared (NIR) spectroscopy can extrapolate tissue oxygenation and may serve as an important tool to assess flap perfusion intraoperatively. This cohort study was undertaken to evaluate the capacity of NIR spectroscopy to detect clinically relevant differences in tissue perfusion intraoperatively. METHODS: Patients undergoing oncologic resection of breast cancer, sarcomas, and cutaneous tumors requiring flap reconstruction (local, regional, or free) between January 2018 and January 2019 were analyzed in this study. Clinicians were blinded to device tissue oxygen saturation (StO2) measurements taken intraoperatively after closure and at follow-up appointments in the first 30 days. Measurements were categorized as (1) control areas not affected by the procedure, (2) areas at risk, and (3) areas of necrosis. These areas were retrospectively demarcated by 2 blinded assessors on follow-up images and transposed onto anatomically correlated intraoperative StO2 measurements. Mean StO2 values were compared using a single-sample t test and analysis of variance (ANOVA) to determine differences in oxygenation. RESULTS: Forty-two patients were enrolled, and 51 images were included in the analysis. Oncologic procedures were predominantly breast (22), postextirpative melanoma (13), and sarcoma (3) reconstructions. Flap reconstruction involved 30 regional skin flaps, 3 pedicled flaps, and 3 free flaps. Nine patients (20.9%) and 11 surgical sites developed SFN. Mean intraoperative StO2 measurements for control areas, areas at risk, and areas of SFN were 74.9%, 71.1%, and 58.3%, respectively. Relative to control areas, mean intraoperative StO2 measurements were lower by 17.5% (P = 0.01) in ultimate areas of SFN and in areas at risk by 5.8% (P = 0.003). Relative to areas at risk, mean StO2 measurements from areas of ultimate SFN were lower by 8.3% (P = 0.04). CONCLUSION: These preliminary data suggest that measuring skin flap tissue oxygenation intraoperatively, with NIR spectroscopy, can differentiate objective variations in perfusion that are associated with clinical outcomes.

Acute Disseminated Intravascular Coagulation After Prophylactic Nailing of the Femur in a Patient with Metastatic Prostate Cancer: A Case Report.

CASE: We present a case of acute disseminated intravascular coagulation (DIC) after prophylactic femoral intramedullary stabilization in a patient with metastatic prostate cancer. Preoperative international normalized ratio of 1.4 was attributed to malnutrition, and the patient was not medically optimized. DIC developed 1 hour postoperatively and was managed with blood product resuscitation. At the 4-month follow-up, the patient presented with bilateral pulmonary emboli and was transitioned to palliative care. CONCLUSIONS: DIC after intramedullary stabilization in patients with metastatic bone disease is a rare condition with high mortality rate. Early recognition, blood product resuscitation, and involvement of appropriate subspecialty services are imperative in DIC management.