Musculoskeletal Tumor Society

Complete removal of all tumor tissue with a wide surgical margin is essential for the treatment of osteosarcoma (OS). However, it's difficult, sometimes impossible, to achieve due to the invisible small satellite lesions and blurry tumor boundaries. Besides, intraoperative frozen-section analysis of resection margins of OS is often restricted by the hard tissues around OS, which makes it impossible to know whether a negative margin is achieved. Any unresected small tumor residuals will lead to local recurrence and worse prognosis. Herein, based on the high expression of B7H3 in OS, a targeted probe B7H3-IRDye800CW is synthesized by conjugating anti-B7H3 antibody and IRDye800CW. B7H3-IRDye800CW can accurately label OS areas after intravenous administration, thereby helping surgeons identify and resect residual OS lesions (<2mm) and lung metastatic lesions. The tumor-background ratio reaches 4.42± 1.77 at day 3. After incubating fresh human OS specimen with B7H3-IRDye800CW, it can specifically label the OS area and even the microinvasion area (confirmed by hematoxylin-eosin [HE] staining). The probe labeled area is consistent with the tumor area shown by magnetic resonance imaging and complete HE staining of the specimen. In summary, B7H3-IRDye800CW has translational potential in intraoperative resection guidance and rapid pathological diagnosis of OS.

High-energy extremity trauma rates can be difficult to precisely state given the complexity of contributing combined mechanisms; however, the rate of open fractures in the United States is 11.5 to 13 per 100,000 people. The management of high-energy extremity fractures presents many challenges for treating surgeons, including elevated risk of surgical site infections (SSIs). In recent studies, higher risk closed injuries are associated with deep SSI rates as high as 19% after surgical treatment and for severe open injuries, which rate surpasses 30%. Fracture-related infections are associated with notable costs and decreased long-term functional outcomes. Identified risk factors for the development of deep SSIs are primarily related to the severity of injury and its location. The quality of the vast literature identifying available interventions to decrease the risk of developing SSIs is highly variable, and it is unclear how consistently these interventions are applied.

Aspirin, as a routine venous thromboembolism (VTE) prophylaxis, is approved along with pneumatic compression pumps by the American College of Chest Physicians. We assessed compliance of aspirin and pump use after total joint arthroplasty. A randomized trial of aspirin alone or aspirin/mobile compression pumps after total joint arthroplasty was performed. Aspirin and pump compliance, VTE events, and satisfaction with pump use were collected. Compliance was assessed through an internal device monitor and drug log book. Patients were also contacted 90 days postoperatively for reported symptomatic VTEs. Each group had 40 patients and greater than 94% compliance with aspirin use, with no difference between groups (P = 0.55). Overall pump compliance during the first 14 days after hospital discharge was 51% (SD ± 33), which was significantly worse than aspirin compliance at 99% (SD ± 4.1) (P < 0.0001). Only 10 patients were compliant (>20 hr/d) with recommended pump use throughout the entire recommended period. There was no notable association between aspirin compliance and VTE within 90 days. There was no notable association between pump compliance and VTE at 90 days. However, average pump use compliance was 20% in patients with VTE and 54% in patients without VTE within 90 days. With the numbers available in this compliance study, there was no significant difference (P = 0.11). Aspirin compliance was notably greater than pump compliance. In this study, we found that pump compliance was not associated with lower VTE risk. In fact, no increased risk was recognized in patients with an average pump usage of >50%. Further study is warranted to define the duration of pump use required for clinical significance. The recommended use of compression pumps should continue to be examined.

ObjectivesThis study aims to: (i) evaluate the outcome of patients with Harrington class III lesions who were treated according to Harrington classification; (ii) propose a modified surgical classification for Harrington class III lesions; and (iii) assess the efficiency of the proposed modified classification.MethodsThis study composes two phases. During phase 1 (2006 to 2011), the clinical data of 16 patients with Harrington class III lesions who were treated by intralesional excision followed by reconstruction of antegrade/retrograde Steinmann pins/screws with cemented total hip arthroplasty (Harrington/modified Harrington procedure) were retrospectively reviewed and further analyzed synthetically to design a modified surgical classification system. In phase 2 (2013 to 2019), 62 patients with Harrington class III lesions were classified and surgically treated according to our modified classification. Functional outcome was assessed using the Musculoskeletal Tumor Society (MSTS) 93 scoring system. The outcome of local control was described using 2‐year recurrence‐free survival (RFS). Owing to the limited sample size, we considered P < 0.1 as significant.ResultsIn phase 1, the mean surgical time was 273.1 (180 to 390) min and the mean intraoperative hemorrhage was 2425.0 (400.0 to 8000.0) mL, respectively. The mean follow‐up time was 18.5 (2 to 54) months. Recurrence was found in 4 patients and the 2‐year RFS rate was 62.4% (95% confidence interval [CI] 31.6% to 93.2%). The mean postoperative MSTS93 score was 56.5% (20% to 90%). Based on the periacetabular bone destruction, we categorized the lesions into two subgroups: with the bone destruction distal to or around the inferior border of the sacroiliac joint (IIIa) and the bone destruction extended proximal to inferior border of the sacroiliac joint (IIIb). Six patients with IIIb lesions had significant prolonged surgical time (313.3 vs 249.0 min, P = 0.022), massive intraoperative hemorrhage (3533.3 vs 1760.0 mL, P = 0.093), poor functional outcome (46.7% vs 62.3%, P = 0.093), and unfavorable local control (31.3% vs 80.0%, P = 0.037) compared to the 10 patients with IIIa lesions. We then modified the surgical strategy for two subgroup of class III lesions: Harrington/modified Harrington procedure for IIIa lesions and en bloc resection followed by modular hemipelvic endoprosthesis replacement for IIIb lesions. Using the proposed modified surgical classification, 62 patients in the phase 2 study demonstrated improved surgical time (245.3 min, P = 0.086), intraoperative hemorrhage (1466.0 mL, P = 0.092), postoperative MSTS 93 scores (65.3%, P = 0.067), and 2‐year RFS rate (91.3%, P = 0.002) during a mean follow‐up time of 19.9 (1 to 60) months compared to those in the phase 1 study.ConclusionThe Harrington surgical classification is insufficient for class III lesions. We proposed modification of the classification for Harrington class III lesions by adding two subgroups and corresponding surgical strategies according to the involvement of bone destruction. Our proposed modified classification showed significant improvement in functional outcome and local control, along with acceptable surgical complexity in surgical management for Harrington class III lesions.

Background:Overexpression of cyclin-dependent kinase 7 (CDK7) is a well-known pathogenic feature of various malignancies and a sign of a more dismal prognosis. As relatively little is known about CDK7 in osteosarcoma, we elected to evaluate its expression, prognostic value, and function.Methods:We began by analyzing the publicly available data sets on CDK7 expression, including RNA sequencing data from the Therapeutically Applicable Research to Generate Effective Treatments on Osteosarcoma (TARGET-OS) and the Gene Expression database of Normal and Tumor tissues 2 (GENT2). The correlation between patient tissue CDK7 expression and their clinicopathological features and prognosis was assessed via immunohistochemical staining of a unique tissue microarray constructed from osteosarcoma specimens. Furthermore, we analyzed CDK7 expression in osteosarcoma cell lines and tissues by Western blot. CDK7-specific siRNA and a highly-selective CDK7 inhibitor, BS-181, were applied to determine the function of CDK7 on osteosarcoma cell growth and proliferation. In addition, the effect of CDK7 inhibition on clonogenicity was evaluated using a clonogenic assay, and a 3D cell culture model was used to mimic CDK7 effects in an in vivo environment.Results:Our results demonstrate that higher CDK7 expression significantly correlates with recurrence, metastasis, and shorter overall survival in osteosarcoma patients. Therapeutically, we show that CDK7 knockdown with siRNA or selective inhibition with BS-181 decreases proliferation and induces apoptosis of osteosarcoma cells.Conclusion:This study supports CDK7 overexpression as an independent predictor of poor prognosis and promising therapeutic target for osteosarcoma.

The purpose of this systematic review and meta-analysis (PROSPERO ID: CRD42021250467) was to evaluate the effects of exercise on low-trauma overall and major osteoporotic fractures (hip, spine, forearm, or humerus fractures) and to determine the corresponding effect of supervision of the exercise program. Our systematic search of six literature databases according to the PRISMA guideline was conducted from January 1, 2013 (ie, date of our last search) to May 22, 2021, and included controlled clinical exercise trials with (i) individuals aged ≥45 years, (ii) cohorts without therapies/diseases related to fractures, (iii) observation periods of ≥3 months, and (iv) the number of low-trauma fractures listed separately for the exercise (EG) and control (CG) groups. We included 20 intervention studies with 21 EGs and 20 CGs comprising a pooled number of participant-years of n= 11.836 in the EG and n= 11.275 in the CG. The mixed-effects conditional Poisson regression revealed significant effects of exercise on low-trauma overall incidence (rate) ratio (IR 0.67, 95% confidence interval [95% CI] 0.51-0.87) and major osteoporotic fractures IR (0.69, 95% CI 0.52-0.92). Heterogeneity between the trials was moderate for low-trauma overall (I2=40%) and negligible (I2 < 1%) for major osteoporotic fractures. Supervision of the exercise program plays a significant role in the reductions of overall and major osteoporotic fractures with IR about twice as favorable in the predominately supervised (IR 0.44; 95% CI 0.27-0.73 and 0.38; 0.19-0.76) versus the predominately non-supervised exercise trials (IR 0.83; 95% CI 0.60-1.14 and 0.82; 0.64-1.05). In summary, the present study provides evidence for the positive effect of exercise on low-trauma overall and major osteoporotic fractures in middle aged to older adults. Supervision of the exercise program is a crucial aspect in exercise programs on fracture reduction. Thus, home-based exercise protocols should increasingly implement online classes to ensure widely consistent supervision and monitoring of the exercise program. © 2022 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).

We retrospectively report our experience of managing 30 patients with a primary malignant tumour of the distal tibia; 25 were treated by limb salvage surgery and five by amputation. We compared the clinical outcomes of following the use of different methods of reconstruction. There were 19 male and 11 female patients. The mean age of the patients was 19 years (6 to 59) and the mean follow-up was 5.1 years (1.25 to 12.58). Massive allograft was used in 11 patients, and autograft was used in 14 patients. The time to union, the survival time of the reconstruction, complication rate, and functional outcomes following the different surgical techniques were compared. The overall patient survival was also recorded. Out of 14 patients treated with an autograft, 12 (86%) achieved union at both the proximal and distal junctions. The time to union at both junctions of the autograft was significantly shorter than in those treated with an allograft (11.1 vs 17.2 months, p = 0.02; 9.5 vs 16.2 months, p = 0.04). The complication rate of allograft reconstruction was 55%. The five patients treated with an amputation did not have a complication. Out of the 25 patients who were treated with limb salvage, three (12%) developed local recurrence and underwent amputation. The mean functional Musculoskeletal Tumor Society (MSTS) score after autograft reconstruction was higher than after allograft reconstruction (81% vs 67%; p = 0.06), and similar to that after amputation (81% vs 82%; p = 0.82). The two- and five-year overall rates of survival were 83% and 70%, respectively. This consecutive case series supports the safety of limb salvage and the effectiveness of biological reconstruction after the resection of a primary tumour of the distal tibia. Autograft might be a preferable option. In some circumstances, below-knee amputation remains a valid option.

Where Are We Now? The improving survival of patients with metastatic bone disease translates into increased disease prevalence that has resulted in a rising cost of care. Our goals as physicians should be to not only alleviate the burden on our patients but also to minimize any unnecessary burden on the healthcare system. In the United States, caring for the more than 250,000 patients who have metastatic bone disease comes at an annual cost of USD 12 billion [1]. Hence, as orthopaedic surgeons, when we consider surgical treatment of these patients, we must do so with an increasing eye on the precise indications for prophylactic fixation as well as the potential morbidity of any surgical intervention. We should strive to only operate prophylactically on patients who truly have impending fractures and on those who are likely to have a better result with prophylactic treatment compared to treating the fracture after the fact. One area of increased scrutiny during the last several years has been the delineation of precise imaging-based indications for prophylactic fixation of impending fractures. Newer techniques, such as CT-based structural rigidity analysis (CTRA), finite element modeling (FEM), and fluorodeoxyglucose positron emission tomography (FDG-PET) CT have been shown to be more accurate in predicting impending fractures than the traditional Harrington and Mirels methods [2, 3, 5-7]. But generally, these techniques are not financially feasible, which limit their availability. Of course, using imaging to identify bone lesions that are biomechanically impending fractures is only part of the equation. Other important variables include patient’s level of pain, disease prognosis, expected response to alternate therapies, comorbidities, and personal goals. Moreover, the risk of treatment complications, as illustrated in the current study [4], should be considered to ensure that prophylactic treatment is at the least not worse than treating the fracture after the fact. In the current study, McLynn and colleagues [4] present their National Surgical Quality Improvement Program (NSQIP)-based complication analysis for the femoral shaft and more distal femur. They found that when controlled for differences in patient characteristics, patients who underwent prophylactic stabilization benefited only in terms of a lower likelihood of transfusion compared to patients treated after a pathologic fracture occurred. The high overall complication (18%), major complication (14%), and death rates (7%) of the prophylactically treated group showed that the risks of prophylactic stabilization are not worse than that of treatment after fracture, and that the advantages are minimal [4]. Obviously, there are some situations where, owing to debilitating pain or failure of other treatments, prophylactic treatment is reasonable even with an equivalent risk compared to postfracture treatment. However, I would contend that the prophylactic treatment outcomes should be clearly safer than that of treatment after the fact. Otherwise, why would we recommend prophylactic treatment in the first place in most patients? Where Do We Need To Go? The current study leaves two questions unanswered. First, are we operating on too many patients for lesions that are not truly impending pathologic fractures? The NSQIP analysis data set does not provide details as to how the decision for prophylactic fixation was made, so we don’t know what percentage of the patients who were prophylactically stabilized actually had impending fractures by well-defined imaging indications. The likelihood of fracture may not be as high as we think. In the prospective Musculoskeletal Tumor Society (MSTS) study evaluating patients with bone lesions for possible impending pathologic fracture using CTRA, 32 patients with 40 lesions underwent prophylactic stabilization [2]. Of the remaining 78 patients (94 lesions) followed prospectively without prophylactic stabilization to endpoints of either 1 year or death, only six patients (six lesions) sustained fractures [2]. It seems that with a more-precise definition of impending pathologic fracture, most patients with lesions would not need operative treatment to prevent fracture since they are not at increased risk. Second, is the patient reported pain and functional outcome, risk profile, and cost-effectiveness of our prophylactic surgical treatment better in terms of pain relief, improved function, lower complications, and better cost-effectiveness than if we had simply treated them nonoperatively? In the current study, the authors compared prophylactically surgically treated patients to those treated surgically after the fracture, but the third undiscussed group is those with possible impending fractures who were treated nonoperatively. Again, the NSQIP database does not provide access to any of the aforementioned details of that group, and the authors acknowledge this. Since nonoperative treatment of patients with possible impending pathologic fractures by other modalities such as radiotherapy, bisphosphonates, chemotherapy, hormonal therapies, or immunomodulation may obviate the need for surgery, it may also eliminate the risks associated with surgery that McLynn and colleagues [4] have documented. With an apparently low risk of overall fracture in this group, as suggested in the MSTS study [2], it is concerning that the risk of complications following prophylactic stabilization is comparable to that of those who already had fractures. For those patients who have not yet fractured, it would seem logical that we should carefully select a treatment—operative or nonoperative—that is not just equivalent to that of operative treatment after fracture but rather superior to such treatment. How Do We Get There? Prophylactic stabilization for patients with metastatic disease to bone can be gratifying both for patient and physician when pain is severe and/or recalcitrant to other treatments, but we must make sure that these prophylactic procedures are both effective and safe. Continued work is needed in this area. The focus moving forward should be on: (1) Using precise impending fracture pathologic imaging definitions and (2) exploring not only the operatively treated patients (prophylactic and postfracture) but also the nonoperatively treated group in our research. With respect to the former, these newer technologies will evolve with time and hopefully become widely available and accepted. Regarding the latter, three possibilities come to mind. First, those patients enrolled in the CTRA study and treated nonoperatively may be compared to those treated prophylactically in terms of complications in the operative group versus fracture and similar complications in the initially nonoperatively treated group, matching for patients deemed to be high or low risk by CTRA. The second will require more time, but as the more precise imaging techniques of CTRA, FEM, and FDG PET/CT are employed, parallel longitudinal data collection should include operative and nonoperative complications, patient-reported outcome measures, survival, cost, and fracture occurrence in the nonoperatively treated group. But it’s not easy to get the major funding necessary to adequately evaluate and employ these techniques on a widespread basis. From the standpoint of developing the individual techniques, CTRA is closest to being thoroughly evaluated and made widely available. The third will require cooperation with radiation and medical oncologists; together we should create longitudinally maintained databases not only of our surgical patients with metastatic disease, but also of those treated without surgery.

To investigate the surgical characteristics and preliminary effectiveness of Orthofix unilateral external fixator in the treatment of musculoskeletal tumors. Twenty-two patients received Orthofix unilateral external fixator treatment for bone defect after tumor excision or complications after limb salvage surgery between June 2011 and March 2016. There were 11 males and 11 females with a median age of 23.5 years (range, 4-57 years). The bone defect or limb length discrepancy after tumor resection was at proximal femur in 6 cases, distal femur in 8 cases, diaphysis of femur in 3 cases, proximal tibia in 2 cases, and diaphysis of tibia in 3 cases. The external fixation was used for temporary fixation after reconstruction of bone defect in 10 cases [the length of bone defect was 6-19 cm (mean, 12.3 cm); using vascularized fibular graft in 2 cases, allograft bone and free fibular graft in 2 cases, allograft bone and autogenous bone graft in 5 cases, allograft bone reconstruction in 1 case]; bone distraction lengthening for limb length discrepancy in 5 cases [the length of shortening was 6.5-8.5 cm (mean, 7.5 cm)]; temporary fixation after open biopsy in 3 cases; bone transportation over locking plate in 1 case (the length of bone defect was 7.5 cm); fixation for preoperatively pathology fracture in 1 case; and joint distraction for dislocation after tumor ablation in 2 cases. All the patients were followed up 12-72 months (mean, 36 months). In 10 patients with bone defect reconstruction, the wearing external fixator time was 3-8 months (mean, 4.8 months); all got bone union with the healing time of 3-16 months (mean, 6.4 months); the Musculoskeletal Tumor Society 93 (MSTS 93) score was 73.3-93.3 (mean, 87.2); and no complication occurred during wearing external fixator. In 5 patients with bone distraction lengthening for limb length discrepancy, the wearing external fixator time was 7-15 months; 2 patients had axial deviation during distraction and2 had greenstick fracture after apparatus removal; pin site infection was observed in 2 cases with grade 1 and 1 case with grade 2 according to Checketts-Otterburn classification system; the MSTS 93 score was 80.0-96.7 (mean, 89.2). The remaining patients had no complications, the knee and ankle joint movement was normal. Orthofix unilateral external fixator can be used in fixation for complex bone defect after tumor resection and to correct limb length discrepancy after limb salvage surgery.