A Prospective Study of the IlluminOss Photodynamic Nail System for Pelvic Stabilization: Treatment of Impending and Actual Fractures from Metastatic Bone Disease, Multiple Myeloma, and Primary Bone Lymphoma.

Background: The stabilization of metastatic lesions in the periacetabular region can be successfully performed using percutaneous techniques. Photodynamic nails (PDNs) are among the available tools for stabilization. Data on postoperative complications and functional outcomes are, however, scarce. Methods: Patients undergoing percutaneous stabilization using PDNs (IlluminOss Medical) for impending or actual minimally displaced pathological fractures of the pelvis from metastatic bone disease, multiple myeloma, or primary bone lymphoma were enrolled prospectively. Outcomes were assessed preoperatively and postoperatively at the 2-day, 2-week, 6-week, 3-month, 6-month, and 1-year time points. Functional outcomes assessed included the Patient-Reported Outcomes Measurement Information System (PROMIS) Physical Function, PROMIS Pain Interference, Combined Pain and Ambulatory Function (CPAF), EuroQol-Visual Analogue Scale (EQ-VAS), and Musculoskeletal Tumor Society (MSTS) scores. Pain was assessed using a VAS. Results: A total of 30 patients treated with PDNs were included. The median VAS pain score dropped from 60 points preoperatively to 30 at 6 weeks postoperatively (p = 0.004). The median CPAF score improved from 6 preoperatively to 7 postoperatively at the 6-week mark. The median EQ-VAS score showed significant improvement at 6 weeks (70 versus 50; p = 0.006). The median 2-week PROMIS Pain Interference score was significantly lower than preoperatively (64.1 versus 66.9; p = 0.03). An improvement in the median PROMIS Physical Function score was seen at 6 weeks following surgery compared with preoperatively (37 versus 30.1; p = 0.001). A significant improvement in the MSTS score was seen as soon as 2 days after surgery (77% versus 40%; p < 0.0001). Conclusions: Among patients with pelvic bone metastases, multiple myeloma, or primary bone lymphoma, we found that treatment using PDNs resulted in immediate return to ambulation and rapid functional outcome improvement, with low complication rates. In this population, this technique represents a safe alternative to open surgery. Level of Evidence: Therapeutic Level IV. See Instructions for Authors for a complete description of levels of evidence.

A dynamic microRNA profile that tracks a chemotherapy resistance phenotype in osteosarcoma. Implications for novel therapeutics.

Osteosarcoma is a rare primary bone tumor for which no significant therapeutic advancement has been made since the late 1980s despite ongoing efforts. Overall, the five-year survival rate remains about 65%, and is much lower in patients with tumors unresponsive to methotrexate, doxorubicin, and cisplatin therapy. Genetic studies have not revealed actionable drug targets, but our group, and others, have reported that epigenomic biomarkers, including regulatory RNAs, may be useful prognostic tools for osteosarcoma. We tested if microRNA (miRNA) transcriptional patterns mark the transition from a chemotherapy sensitive to resistant tumor phenotype. Small RNA sequencing was performed using 14 patient matched pre-chemotherapy biopsy and post-chemotherapy resection high-grade osteosarcoma frozen tumor samples. Independently, small RNA sequencing was performed using 14 patient matched biopsy and resection samples from untreated tumors. Separately, miRNA specific Illumina DASL arrays were used to assay an independent cohort of 65 pre-chemotherapy biopsy and 26 patient matched post-chemotherapy resection formalin fixed paraffin embedded (FFPE) tumor samples. mRNA specific Illumina DASL arrays were used to profile 37 pre-chemotherapy biopsy and five post-chemotherapy resection FFPE samples, all of which were also used for Illumina DASL miRNA profiling. The National Cancer Institute Therapeutically Applicable Research to Generate Effective Treatments dataset, including PCR based miRNA profiling and RNA-seq data for 86 and 93 pre-chemotherapy tumor samples, respectively, was also used. Paired differential expression testing revealed a profile of 17 miRNAs with significantly different transcriptional levels following chemotherapy. Genes targeted by the miRNAs were differentially expressed following chemotherapy, suggesting the miRNAs may regulate transcriptional networks. Finally, an in vitro pharmacogenomic screen using miRNAs and their target transcripts predicted response to a set of candidate small molecule therapeutics which potentially reverse the chemotherapy resistance phenotype and synergize with chemotherapy in otherwise treatment resistant tumors. Importantly, these novel therapeutic targets are distinct from targets identified by a similar pharmacogenomic analysis of previously published prognostic miRNA profiles from pre chemotherapy biopsy specimens.

Debridement, Antibiotics, and Implant Retention (DAIR) Plus Offers Similar Periprosthetic Joint Infection Treatment Success Rates to Two-Stage Revision in Oncologic Megaprosthesis.

BACKGROUND: Prosthetic joint infections (PJIs) after megaprosthesis implantation are associated with high rates of treatment failure and amputation. Our study analyzed PJI treatment success rates by surgical strategy and assessed risks of reinfection and amputation. METHODS: We retrospectively analyzed the outcomes of patients diagnosed with PJI after undergoing megaprosthesis implantation for oncologic indications. The 2011 Musculoskeletal Infection Society criteria were used to define PJI. Reinfection, reoperation, and amputation for PJI recurrence were assessed. A total of 67 patients with megaprosthesis PJIs were included. There were fourteen patients who were treated with debridement, antibiotics, and implant retention (DAIR), 31 with DAIR plus (DAIR with modular component exchange and stem retention), and 21 with two-stage revisions. Kaplan-Meier estimates were used for survival analyses and Cox proportional hazards for risk factor analyses. RESULTS: The two-year reinfection-free survival was 25% for DAIR and 60% for DAIR plus or two-stage revision (P = .049). The five-year amputation-free survival was 84% for DAIR plus or two-stage revision, and 48% for DAIR (P = .13). Reinfection-free, reoperation-free, and amputation-free survival were similar between DAIR plus and two-stage revision at the 2- and 5-year marks. Body mass index ≥30 (hazard ratio [HR] = 2.65) and chronic kidney disease (HR = 11.53) were risk factors for reinfection. Treatment with DAIR plus or two-stage revision (HR = 0.44) was a protective factor against reinfection. CONCLUSIONS: A DAIR was associated with high rates of treatment failure and higher amputation rates than DAIR plus or 2-stage surgery. A DAIR plus was not inferior to 2-stage revision clearing a PJI and might be performed in patients who cannot withstand two-stage revision surgery.

Prediction of 5-year survival in soft tissue leiomyosarcoma using a machine learning model algorithm.

BACKGROUND AND OBJECTIVES: Leiomyosarcoma (LMS) is associated with one of the poorest overall survivals among soft tissue sarcomas. We sought to develop and externally validate a model for 5-year survival prediction in patients with appendicular or truncal LMS using machine learning algorithms. METHODS: The Surveillance, Epidemiology, and End Results (SEER) database was used for development and internal validation of the models; external validation was assessed using our institutional database. Five machine learning algorithms were developed and then tested on our institutional database. Area under the receiver operating characteristic curve (AUC) and Brier score were used to assess model performance. RESULTS: A total of 2209 patients from the SEER database and 81 patients from our tertiary institution were included. All models had excellent calibration with AUC 0.84-0.85 and Brier score 0.15-0.16. After assessing the performance indicators according to the TRIPOD model, we found that the Elastic-Net Penalized Logistic Regression outperformed other models. The AUCs of the institutional data were 0.83 (imputed) and 0.85 (complete-case analysis) with a Brier score of 0.16. CONCLUSION: Our study successfully developed five machine learning algorithms to assess 5-year survival in patients with LMS. The Elastic-Net Penalized Logistic Regression retained performance upon external validation with an AUC of 0.85 and Brier score of 0.15.

Prognostic Significance of Percentage and Size of Dedifferentiation in Dedifferentiated Chondrosarcoma.

Dedifferentiated chondrosarcoma is rare, aggressive, and microscopically bimorphic. How pathologic features such as the amounts of dedifferentiation affect prognosis remains unclear. We evaluated the percentages and sizes of dedifferentiation in a consecutive institutional series of dedifferentiated chondrosarcomas from 1999 to 2021. The statistical analysis included cox proportional hazard models and log-rank tests. Of the 67 patients (26 women, 41 men; age, 39 to >89 [median 61] years; 2 with Ollier disease), 58 presented de novo; 9 were identified with conventional chondrosarcomas 0.6-13.2 years (median, 5.5 years) prior. Pathologic fracture and distant metastases were noted in 27 and 7 patients at presentation. The tumors involved the femur (n = 27), pelvis (n = 22), humerus (n = 7), tibia (n = 4), scapula/ribs (n = 4), spine (n = 2), and clivus (n = 1). In the 56 resections, the tumors ranged in size from 3.5 to 46.0 cm (median, 11.5 cm) and contained 1%-99.5% (median, 70%) dedifferentiated components that ranged in size from 0.6 to 24.0 cm (median, 7.3 cm). No correlation was noted between total size and percentage of dedifferentiation. The dedifferentiated components were typically fibrosarcomatous or osteosarcomatous, whereas the associated cartilaginous components were predominantly grade 1-2, rarely enchondromas or grade 3. The entire cohort's median overall survival and progression-free survival were 11.8 and 5.4 months, respectively. In the resected cohort, although the total size was not prognostic, the percentage of dedifferentiation ≥20% and size of dedifferentiation >3.0 cm each predicted worse overall survival (9.9 vs 72.5 months; HR, 3.76; 95% CI, 1.27-11.14; P = .02; 8.7 vs 58.9 months; HR, 3.03; 95% CI, 1.21-7.57; P = .02, respectively) and progression-free survival (5.3 vs 62.1 months; HR, 3.05; 95% CI, 1.13-8.28; P = .03; 5.3 vs 56.6 months; HR, 2.50; 95% CI, 1.06-5.88; P = .04, respectively). In conclusion, both the percentages and sizes of dedifferentiation were better prognostic predictors than total tumor sizes in dedifferentiated chondrosarcomas, highlighting the utility of their pathologic evaluations.

What Are the Functional and Surgical Outcomes of Tibial Turnup-plasty for Salvage in Patients With Chronic Lower Extremity Infection?

BACKGROUND: Tibial turnup-plasty is a rarely performed surgical option for large bone defects of the distal or entire femur and can serve as an alternative to hip disarticulation or high above-knee amputation. It entails pedicled transport of the ipsilateral tibia with or without the proximal hindfoot for use as a vascularized autograft. It is rotated 180° in the coronal or sagittal plane to the remaining proximal femur or pelvis, augmenting the functional length of the thigh. Prior reports consist of small case series with heterogeneous surgical techniques. Patient-reported outcome measures after the procedure have not been reported, and ambulatory status after the procedure is also unknown. QUESTIONS/PURPOSES: (1) What proportion of patients underwent reoperation after tibial turnup-plasty? (2) What is the ambulatory status and what proportion of patients used a prosthesis after tibial turnup-plasty? (3) What are the Patient-Reported Outcome Measurement Information System (PROMIS) Global-10 mental and physical function scores after tibial turnup-plasty? METHODS: A retrospective analysis was performed of 11 patients who underwent tibial turnup-plasty between 2003 and 2021 by a single orthopaedic oncology division in collaboration with a reconstructive plastic surgery team. Nine patients were men, with a median age of 55 years (range 34 to 75 years). All had chronic infections after arthroplasty or oncologic reconstructions, with a median number of 13 surgeries before turnup-plasty. All were considered to have no other surgical options other than hip disarticulation or high transfemoral amputation. All patients who were offered this possibility accepted it. Data of interest included patient demographics and comorbidities, surgical history that led to limb compromise, medical and surgical perioperative complications, date of prosthesis fitting, and functional capacity at the most recent follow-up interval based on ambulatory status and PROMIS Global-10 mental and physical function scores. The statistical analysis was descriptive. RESULTS: The median number of reoperations after turnup-plasty was one (range 0 to 11). Of the six patients who underwent at least one reoperation, indications for surgery included wound infection (four patients), nonunion of the osteosynthesis site (two), heterotopic ossification (one), tumor recurrence (one), and flap hypoperfusion treated with local tissue revision (one). One patient underwent conversion to external hemipelvectomy for tumor recurrence. Ten of the 11 patients were ambulatory at the final follow-up interval with standard above-knee amputation prostheses. Two ambulated unassisted, four used a single crutch or cane, and four used two crutches or a walker. Of the nine patients for whom scores were available, the median PROMIS Global-10 physical and mental health scores were 48 (range 30 to 68) and 53 (range 41 to 68), both within the standard deviation of the population mean of 50. CONCLUSION: The tibial turnup-plasty is a complex surgical option for patients with large bone defects of the femur for whom there are no alternative surgeries capable of producing residual extremities with acceptable functional length. This should be viewed as a procedure of last resort to avoid a hip disarticulation or a high transfemoral amputation in patients who have typically undergone numerous prior operations. Although ambulation with a prosthesis within 1 year can be expected, almost all patients will require an assistive device to do so, and reoperations are frequent. LEVEL OF EVIDENCE: Level IV, therapeutic study.

The impact of radiotherapy on survival after surgical resection of chordoma with minimum five-year follow-up.

BACKGROUND CONTEXT: Local control remains a vexing problem in the management of chordoma despite advances in operative techniques and radiotherapy (RT) protocols. Existing studies show satisfactory local control rates with different treatment modalities. However, those studies with minimum follow-up more than 4 years demonstrate increasing rates of local failure. Therefore, mid-term local survival rates may be inadvertently elevated by studies with less than 4 years follow-up. PURPOSE: The purpose of this study is to report the mid-term results of primary spinal chordoma treated with en bloc resection and proton-based RT with minimum 5 years of follow-up. STUDY DESIGN/SETTING: Retrospective, single-center, cohort study. PATIENT SAMPLE: Patients undergoing primary surgical excision of a spine or sacral chordoma tumor between 1990 and 2016 at a single-institution were included. Patients were included if they had a local failure at any time, or they had a minimum of 5 years of follow up with no local failure. Patients were excluded if a prior surgical excision was performed or metastases were present at the time of referral. OUTCOME MEASURES: The outcome measures were local recurrence-free interval (LRFI) and overall survival (OS). METHODS: Demographic, clinical, oncologic and surgical variables, including margin status, as well as radiation doses and schedule (neoadjuvant, adjuvant, or both) were compared using Wilcoxon rank-sum or chi-squared testing. The goal RT dose was 70 Gray (total) and patients were stratified based on completing (C70) or receiving incomplete (I70) dosing. Overall survival (OS) and local-recurrence free interval (LRFI) were calculated using the Kaplan-Meier method. FUNDING STATEMENT: No funding was obtained for this work. RESULTS: Seventy-six patients were included in the final analysis. All patients had a minimum of 5-year follow-up (median 9.3 years, range 5.1-24.7 years). There were no significant clinical differences between the C70 and I70 RT groups. OS was greater for the C70 RT group (5-year OS 82% vs. 63%, p=.001). There was similar OS for the positive margin group (5-year OS 70% vs. 61%, p=.266). LRFI was greater for the C70 RT group (5-year OS 93% vs. 78%, p=.017). There was similar LRFI for the positive margin group (5-year OS 90% versus 87%, p=.810). CONCLUSION: Chordoma outcomes trend towards diminishing LRFI rates in the literature. Here we report the results of the operative management of primary spinal chordoma with minimum five year follow-up, the addition of C70 RT to surgical excision conferred a benefit to OS and local recurrence.

Metastatic Uterine Leiomyosarcoma With Rhabdomyosarcomatous Heterologous Differentiation.

Heterologous differentiation has only been previously reported twice in metastatic uterine leiomyosarcomas. We report herein the first case of metastatic uterine leiomyosarcoma with rhabdomyosarcomatous differentiation. A 67-yr-old woman presented with femur, abductor magnus, and lymph node metastases 9 yr after the primary diagnosis. The metastatic sites showed rhabdomyosarcomatous morphologic features, and immunohistochemical studies confirmed skeletal muscle differentiation. Molecular testing revealed the same loss-of-function TP53 mutation in the uterine leiomyosarcoma and metastatic sites supporting heterologous differentiation of the primary tumor. Our case highlights the morphologic shifts metastatic tumors may manifest and the potential diagnostic problems that may arise.

Trabecular metal augments in severe malignancy-associated acetabular bone loss.

INTRODUCTION: Acetabular reconstruction is a challenging problem in orthopaedic oncology, especially in extended defects (Paprosky Type 3A and Type 3B). In revision total hip arthroplasty (THA), 1 option is trabecular metal (TM) augments with a porous metal acetabular component. This study evaluated the use of TM augments in periacetabular malignant bone disease. METHODS: 15 patients were identified from our institutional database from 2000 to 2020 with either Paprosky Type 3A or Type 3B acetabular bone loss due to periacetabular malignancies that underwent at least 1 complex THA reconstruction with TM augments. Postoperative complications were documented, and clinical and radiographic outcomes were analysed. Radiological loosening or revision of the acetabular component were defined as endpoints. RESULTS: There were 7 primary and 8 metastatic cancer patients. 5 were Type 3A and 10 were Type 3B defects after tumour resection. The average follow-up time was 23.8 (range 1.5-47) months. 1 patient required revision for acetabular component loosening after 7 months from the initial implantation. An additional 4 patients required surgical intervention for infection, they had stable TM augments at latest follow-up. CONCLUSION: TM augments with a porous metal acetabular component may be an alternative to the traditional cemented constructs.

Comparison of carbon fibre and titanium intramedullary nails in orthopaedic oncology.

AIMS: Due to their radiolucency and favourable mechanical properties, carbon fibre nails may be a preferable alternative to titanium nails for oncology patients. We aim to compare the surgical characteristics and short-term results of patients who underwent intramedullary fixation with either a titanium or carbon fibre nail for pathological long-bone fracture. METHODS: This single tertiary-institutional, retrospectively matched case-control study included 72 patients who underwent prophylactic or therapeutic fixation for pathological fracture of the humerus, femur, or tibia with either a titanium (control group, n = 36) or carbon fibre (case group, n = 36) intramedullary nail between 2016 to 2020. Patients were excluded if intramedullary fixation was combined with any other surgical procedure/fixation method. Outcomes included operating time, blood loss, fluoroscopic time, and complications. Fisher's exact test and Mann-Whitney U test were used for categorical and continuous outcomes, respectively. RESULTS: Patients receiving carbon nails as compared to those receiving titanium nails had higher blood loss (median 150 ml (interquartile range (IQR) 100 to 250) vs 100 ml (IQR 50 to 150); p = 0.042) and longer fluoroscopic time (median 150 seconds (IQR 114 to 182) vs 94 seconds (IQR 58 to 124); p = 0.001). Implant complications occurred in seven patients (19%) in the titanium group versus one patient (3%) in the carbon fibre group (p = 0.055). There were no notable differences between groups with regard to operating time, surgical wound infection, or survival. CONCLUSION: This pilot study demonstrates a non-inferior surgical and short-term clinical profile supporting further consideration of carbon fibre nails for pathological fracture fixation in orthopaedic oncology patients. Given enhanced accommodation of imaging methods important for oncological surveillance and radiation therapy planning, as well as high tolerances to fatigue stress, carbon fibre implants possess important oncological advantages over titanium implants that merit further prospective investigation. Level of evidence: III, Retrospective study Cite this article: Bone Jt Open 2022;3(8):648-655.

Primary and Metastatic Bone Tumors of the Patella: Literature Review and Institutional Experience.

Background: Patellar tumors are rare but certainly must be considered in the differential diagnosis in patients with knee pain. Diagnosis can be challenging as often patellar neoplasms are confused with benign conditions and their clinical presentation is usually not specific. We performed an institutional and a literature review to determine what are the most common tumors affecting the patella and what is the best management. Methods: This is a case series from our institution including all patients with benign, malignant, and metastatic patellar neoplasms. Charts were reviewed for patient demographics, clinical presentation, pathology characteristics, radiographic classification, and oncologic and functional outcomes. Results: Twenty-four patients were identified; twelve patients had benign lesions, 10 metastatic and 2 primary malignant tumors. Chondroblastoma and Giant Cell Tumor were the most common tumors. Management of benign lesions with intralesional curettage and packing with bone graft or cement demonstrated excellent results with no local recurrence. In terms of malignant tumors, the spectrum of treatment is variable; it could range from medical management alone or in combination with surgical procedures to total patellectomy with reconstruction of the extensor mechanism. Conclusion: Patellar tumors should be part of the differential in patients with chronic knee pain that does not respond to initial conservative interventions. Recurrence rate with intralesional curettage and bone grafting or cement packing is very low and therefore should be the treatment of choice for benign intraosseous neoplasms. Resection with negative margins in malignant neoplasms or bone metastasis decreases local recurrence but only in the former group there is a potential impact in survival.

Sclerostin immunohistochemical staining in surgically treated giant cell tumor of bone.

BACKGROUND: Giant cell tumor of bone (GCTB) is a destructive lesion with a high potential for recurrence. RANK-ligand targeted therapy has provided promising, yet mixed results. Sclerostin (SOST) inhibition results in a net anabolic response and is currently used in the treatment of osteoporosis. The application to GCTB is unknown. OBJECTIVES: We sought to determine if GCTB stained for SOST on immunohistochemistry and correlate its expression with predictor variables. METHODS: All patients at a single institution undergoing surgery for GCTB between 1993 and 2008 with a minimum of 6 months follow-up were included. Primary outcomes included the presence of SOST staining, secondary outcomes included the correlation of patient and tumor-specific predictor variables. RESULTS: SOST antibody staining of any cell type was present in 47 of 48 cases (97.9%). Positivity of the stromal cells was present in 39 of 48 cases (81.3%) and was associated with radiographic aggressiveness (p = 0.023), symptomatic presentation (p = 0.032), prior surgery (p = 0.005), and patient age (p = 0.034). Positivity of giant cells was present in 41 of 48 cases (85.4%) and was not significant with predictive factors. CONCLUSIONS: Sclerostin staining in GCTB is a novel finding and warrants further research to define the role of sclerostin as a prognostic factor and therapeutic target.

Genome-wide DNA methylation patterns reveal clinically relevant predictive and prognostic subtypes in human osteosarcoma.

Aberrant methylation of genomic DNA has been reported in many cancers. Specific DNA methylation patterns have been shown to provide clinically useful prognostic information and define molecular disease subtypes with different response to therapy and long-term outcome. Osteosarcoma is an aggressive malignancy for which approximately half of tumors recur following standard combined surgical resection and chemotherapy. No accepted prognostic factor save tumor necrosis in response to adjuvant therapy currently exists, and traditional genomic studies have thus far failed to identify meaningful clinical associations. We studied the genome-wide methylation state of primary tumors and tested how they predict patient outcomes. We discovered relative genomic hypomethylation to be strongly predictive of response to standard chemotherapy. Recurrence and survival were also associated with genomic methylation, but through more site-specific patterns. Furthermore, the methylation patterns were reproducible in three small independent clinical datasets. Downstream transcriptional, in vitro, and pharmacogenomic analysis provides insight into the clinical translation of the methylation patterns. Our findings suggest the assessment of genomic methylation may represent a strategy for stratifying patients for the application of alternative therapies.

Tumors and Tumorlike Conditions of Which Every Orthopaedic Surgeon Should Be Aware.

All orthopaedic surgeons during the course of their career will likely encounter both benign and malignant musculoskeletal neoplasms. Given the rarity of these entities and the stress conferred by diagnosing a tumor or tumorlike condition, many orthopaedic surgeons may benefit from a review of the contemporary treatment of such patients. Whether in the outpatient clinic or following a high-energy trauma, special attention should be given to concerning signs and symptoms that will aid in the workup of children and adults with a possible tumor. A thorough and logical workup in this manner will often lead to a definitive diagnosis such as metastatic bone disease or perhaps a benign lesion. In these instances, the informed general orthopaedic surgeon or subspecialist may choose to treat the patient independently. However, if the workup is inconclusive or if the diagnosis is even questionably malignant, referral to an orthopaedic oncologist should be sought as to avoid pitfalls in diagnosis and treatment.

Tubercle-Sparing Proximal Tibial Reconstruction in Patients with Primary and Metastatic Bone Disease: A Case Report.

CASE: Two patients with cancer involving their proximal tibia required proximal tibial replacement (PTR). One had a soft-tissue sarcoma that involved her posterior cortex, and the other had extensive metaphyseal destruction from metastatic breast cancer. Their anterolateral cortex and tibial tubercle were uninvolved, permitting tubercle-sparing PTR. A plate was applied to the bone bridge in the latter patient in anticipation of radiotherapy. Both healed uneventfully and had minimal extensor lag 2 weeks postoperatively. CONCLUSION: Tubercle-sparing PTR preserves extensor mechanism function with minimal lag. It should be considered in patients with cancer when sparing the anterolateral cortex is oncologically safe.

Assessing the Safety and Utility of Wound VAC Temporization of the Sarcoma or Benign Aggressive Tumor Bed Until Final Margins Are Achieved.

BACKGROUND: Local recurrence of microinvasive sarcoma or benign aggressive pathologies can be limb- and life-threatening. Although frozen pathology is reliable, tumor microinvasion can be subtle or missed, having an impact on surgical margins and postoperative radiation planning. The authors' service has begun to temporize the tumor bed after primary tumor excision with a wound vacuum-assisted closure (VAC) pending formal margin analysis, with coverage performed in the setting of final negative margins. METHODS: This retrospective analysis included all patients managed at a tertiary referral cancer center with VAC temporization after soft tissue sarcoma or benign aggressive tumor excision from 1 January 2000 to 1 January 2019 and at least 2 years of oncologic follow-up evaluation. The primary outcome was local recurrence. The secondary outcomes were distant recurrence, unplanned return to the operating room for wound/infectious indications, thromboembolic events, and tumor-related deaths. RESULTS: For 62 patients, VAC temporization was performed. The mean age of the patients was 62.2 ± 22.3 years (median 66.5 years; 95% confidence interval [CI] 61.7-72.5 years), and the mean age-adjusted Charlson Comorbidity Index was 5.3 ± 1.9. The most common tumor histology was myxofibrosarcoma (51.6%, 32/62). The mean volume was 124.8 ± 324.1 cm3, and 35.5% (22/62) of the cases were subfascial. Local recurrences occurred for 8.1% (5/62) of the patients. Three of these five patients had planned positive margins, and 17.7% (11/62) of the patients had an unplanned return to the operating room. No demographic or tumor factors were associated with unplanned surgery. CONCLUSIONS: The findings showed that VAC-temporized management of microinvasive sarcoma and benign aggressive pathologies yields favorable local recurrence and unplanned operating room rates suggestive of oncologic and technical safety. These findings will need validation in a future randomized controlled trial.

Clinical Outcome Differences in the Treatment of Impending Versus Completed Pathological Long-Bone Fractures.

BACKGROUND: The outcome differences following surgery for an impending versus a completed pathological fracture have not been clearly defined. The purpose of the present study was to assess differences in outcomes following the surgical treatment of impending versus completed pathological fractures in patients with long-bone metastases in terms of (1) 90-day and 1-year survival and (2) intraoperative blood loss, perioperative blood transfusion, anesthesia time, duration of hospitalization, 30-day postoperative systemic complications, and reoperations. METHODS: We retrospectively performed a matched cohort study utilizing a database of 1,064 patients who had undergone operative treatment for 462 impending and 602 completed metastatic long-bone fractures. After matching on 22 variables, including primary tumor, visceral metastases, and surgical treatment, 270 impending pathological fractures were matched to 270 completed pathological fractures. The primary outcome was assessed with the Cox proportional hazard model. The secondary outcomes were assessed with the McNemar test and the Wilcoxon signed-rank test. RESULTS: The 90-day survival rate did not differ between the groups (HR, 1.13 [95% CI, 0.81 to 1.56]; p = 0.48), but the 1-year survival rate was worse for completed pathological fractures (46% versus 38%) (HR, 1.28 [95% CI, 1.02 to 1.61]; p = 0.03). With regard to secondary outcomes, completed pathological fractures were associated with higher intraoperative estimated blood loss (p = 0.03), a higher rate of perioperative blood transfusions (p = 0.01), longer anesthesia time (p = 0.04), and more reoperations (OR, 2.50 [95% CI, 1.92 to 7.86]; p = 0.03); no differences were found in terms of the rate of 30-day postoperative complications or the duration of hospitalization. CONCLUSIONS: Patients undergoing surgery for impending pathological fractures had lower 1-year mortality rates and better secondary outcomes as compared with patients undergoing surgery for completed pathological fractures when accounting for 22 covariates through propensity matching. Patients with an impending pathological fracture appear to benefit from prophylactic stabilization as stabilizing a completed pathological fracture seems to be associated with increased mortality, blood loss, rate of blood transfusions, duration of surgery, and reoperation risk. LEVEL OF EVIDENCE: Prognostic Level III. See Instructions for Authors for a complete description of levels of evidence.

Sclerostin Immunohistochemical Staining in Aggressive Maxillofacial Giant Cell Lesions: Initial Results and Potential Therapeutic Target.

INTRODUCTION: Maxillofacial (MF) giant cell lesions (GCLs) are benign, often locally aggressive lesions with potential for recurrence. Systemic treatments have included interferon alpha, calcitonin, bisphosphonates, and denosumab. Sclerostin (SOST) is typically thought to be a negative regulator of bone metabolism and anti-SOST agents have been used to treat osteoporosis; however, its role in central giant cell granuloma is unknown. The purpose of this study was to evaluate the expression of SOST in MF GCLs. MATERIALS AND METHODS: This was a retrospective study of patients with MF GCLs treated at a single institution between 1993 and 2008 with a minimum follow-up of 6 months. Representative tissue was used to create a tissue microarray and SOST immunohistochemical (IHC) staining and grading was performed. The primary outcomes were IHC staining of the stromal cells and giant cells. The secondary outcomes included correlation of IHC staining and patient predictor variables including clinically benign and aggressive lesions. All analyses were completed using univariate statistical tests. RESULTS: A total of 37 subjects were included (29 clinically aggressive and 8 clinically benign). Sclerostin staining was present in 30 of 37 subjects (81%). Of these, 22 (60%) had stromal cell staining and 28 (76%) had giant cell staining. The presence or absence of staining, of either cell type, was not associated with aggressiveness, presence of clinical symptoms, tumor size, previous interferon therapy, previous surgery, or the race or age of the patient. DISCUSSION: Maxillofacial GCLs have an overall high level of SOST staining; however, the role of SOST in treatment and prognosis is unknown and warrants further study.

Pseudoprogression of Malignant Peripheral Nerve Sheath Tumor in Patient with Neurofibromatosis Type 1, a Case Report.

Pseudoprogression, defined as the radiographic false appearance of disease progression, is not frequently observed in patients with malignant peripheral nerve sheath tumor (MPNST). We report on a case of a patient with neurofibromatosis type 1 (NF1) MPNST pseudoprogression that presented as suspected local recurrence 9.5 years after last treatment. The patient underwent surgical resection following growth of a mass on sequential MRI imaging; surgical pathology, however, showed skeletal muscle with atrophy, fibroadipose tissue, and fat necrosis, without any evidence of tumor. As MPNST survival rates increase, physicians should consider pseudoprogression as a potential presentation after prior treatment.