Intraoperative Evaluation of Soft Tissue Sarcoma Surgical Margins with Indocyanine Green Fluorescence Imaging.

Soft tissue sarcomas (STS) are rare malignant tumors often associated with poor outcomes and high local recurrence rates. Current tools for intraoperative and definitive margin assessment include intraoperative frozen section and permanent pathology, respectively. Indocyanine green dye (ICG) is a historically safe fluorophore dye that has demonstrated efficacy for intraoperative margin assessment in the surgical management of both breast and gastrointestinal cancers. The utility of ICG in the surgical management of sarcoma surgery has primarily been studied in pre-clinical mouse models and warrants further investigation as a potential adjunct to achieving negative margins. This study is a prospective, non-randomized clinical study conducted on patients with confirmed or suspected STS. Patients younger than 18 years, with a prior adverse reaction to iodine or fluorescein, or with renal disease were excluded from the study. Intravenous ICG was infused approximately three hours prior to surgery at a dosage of 2.0-2.5 mg/kg, and following tumor resection, the excised tumor and tumor bed were imaged for fluorescence intensity. When scanning the tumor bed, a threshold of 77% calibrated to the region of maximum intensity in the resected tumor was defined as a positive ICG margin, according to published protocols from the breast cancer literature. ICG results were then compared with the surgeon's clinical impression of margin status and permanent pathology results. Out of 26 subjects recruited for the original study, 18 soft tissue sarcomas (STS) were included for analysis. Three subjects were excluded for having bone sarcomas, and five subjects were excluded due to final pathology, which was ultimately inconsistent with sarcoma. The average age of patients was 64.1 years old (range: 28-83), with an average ICG dose of 201.8 mg. In 56% (10/18) of patients, ICG margins were consistent with the permanent pathology margins, with 89% specificity. The use of ICG as an intraoperative adjunct to obtaining negative margins in soft tissue sarcoma surgery is promising. However, studies with larger sample sizes are warranted to further delineate the accuracy, optimal dosage, timing, and types of sarcoma in which this diagnostic tool may be most useful.

Residual limb shear strain during gait is correlated with patient reported outcomes for persons with transfemoral amputation.

The purpose of this study was to measure residual limb skin strain and strain rate within the socket during gait in individuals with a transfemoral amputation and to determine if skin strain during gait is related to patient-reported comfort and function. It was hypothesized that greater skin strain and skin strain rate would correlate to worse patient-reported outcomes. It was also hypothesized that skin strain would progressively increase from the distal to the proximal end of the residuum and maximum strain would occur shortly after heel strike. Dynamic biplane radiography (DBR), combined with conventional motion capture, was used to measure skin deformation within the socket during treadmill walking for 10 persons with unilateral transfemoral amputation. The questionnaire for persons with a transfemoral amputation (Q-TFA) was administered to assess prosthetic use, mobility, health problems, and global health. Q-TFA Prosthetic Use score and Problem score were negatively correlated with the peak shear strains in the proximal and distal regions of the residuum, respectively. Maximum shear strain increased progressively from proximal to distal regions of the residual limb. Within-subject variability in shear strain waveforms during gait was 0.7% or less, but between-subject variability was 3.3% to 5.0% shear. This study demonstrates that skin shear within the socket of persons with transfemoral amputation can be measured during gait using DBR and the results suggest that greater skin shear in the proximal region of the socket is related to decreased prosthetic use.

Novel MEAF6-SUZ12 fusion in ossifying fibromyxoid tumor with unusual features.

Ossifying fibromyxoid tumor (OFMT) is a rare soft tissue neoplasm of uncertain differentiation that has the capacity for local recurrence and metastasis. Many OFMTs, including typical, atypical, and malignant tumors, have demonstrated recurrent gene fusions. The fusion partners reported to date share a common core function in that they play either a direct or indirect role in processes influencing histone modification. Herein, we report an OFMT with unusual morphology and non-specific immunoprofile harboring a novel MEAF6-SUZ12 fusion. A 34-year-old male presented with a slowly growing mass in the right antecubital fossa. Excision demonstrated a 6.9 cm partially encapsulated, tan-white, lobulated, and calcified lesion. Microscopic evaluation demonstrated cytologically bland spindle to ovoid cells arranged in a haphazard manner within a fibromyxoid background containing dense collagen, often with sclerotic nodules, and randomly distributed ossification. The tumor cells were diffusely positive for CD34 while essentially negative for S100, desmin, MUC4, SOX10, AE1/3, SMA, and EMA. Next-generation sequencing studies (sarcoma gene fusion next-generation sequencing panel with subsequent Sanger confirmation) performed on formalin-fixed paraffin-embedded tissue detected a fusion product between MEAF6 exon 4 (NM_001270875) and SUZ12 exon 2 (NM_001321207.1). The proposed mechanism of pathogenesis in OFMT, namely epigenetic dysregulation, is reinforced by the fact that both of these partner genes are involved in histone modification.

Motion of the residual femur within the socket during gait is associated with patient-reported problems in transfemoral amputees.

The purpose of this study was to provide a quantitative description of residual femur motion within the socket during gait and to explore the relationship between residual femur motion and patient-reported comfort and function. It was hypothesized that increased residual bone movement would correlate to worse patient-reported comfort and function. The secondary goals were to assess within-subject step-to-step variability and between-subject variability in residual femur motion within the socket during gait. Dynamic biplane radiography, combined with conventional motion capture, was used to measure residual femur motion within the socket during treadmill walking for 10 unilateral transfemoral amputees. The questionnaire for persons with a transfemoral amputation (Q-TFA) was administered to assess prosthetic use, mobility, health problems, and global health. Increased femur pistoning (proximal-distal translation relative to the socket) correlated with worsening Q-TFA problem and global scores (ρ = 0.741, p = 0.04 and ρ = -0.783, p = 0.02, respectively). Average residual femur rotation ROMs were 7.3°±3.7°, 10.8°±4.4°, and 7.7°±4.8° for anterior tilt, internal-external rotation, and varus-valgus, respectively. Average residual femur translation ROMs were 8.6 mm ± 3.0 mm, 28.4 mm ± 13.9 mm, and 20.4 mm ± 7.2 mm for medial-lateral, pistoning, and anterior-posterior directions, respectively. Within-subject rotational and translational variability during gait averaged 2.8° and 2.0 mm or less, whereas the between-subject variability was up to 9.4° and 18.6 mm, which demonstrates residual femur motion relative to the socket is repeatable within subjects, but inconsistent across subjects during gait. The results suggest residual bone motion within the socket is a potential mechanism behind patient-reported problems and suggests a target for intervention aimed at improving transfemoral amputee quality of life.

Evaluating the reoperation rate and hardware durability of three stabilizing implants for 105 malignant pathologic humerus fractures.

INTRODUCTION: Many patients sustaining a malignant pathologic humerus fracture (MPHF) elect for surgical stabilization. Complications prompting reoperation can occur, leading to additional quality of life and financial cost. One common event preceding reoperation is a broken implant (BI). The purpose of this study was to identify the rate of reoperation following surgical stabilization of MPHF with three techniques - photodynamic bone stabilization (PBS), intramedullary nail (IMN), and cemented plate fixation (CPF) - and estimate to what extent improved implant durability might prevent reoperation. MATERIALS AND METHODS: Retrospective data collection was performed, identifying 105 procedures (100 patients) who underwent non-articular MPHF surgery from 2010-2016: 19 PBS, 65 IMN, 21 CPF. All patients were followed for at least two years or until death. RESULTS: Reoperation rates were similar at one year (10.5%,6.2%,4.8%, p = 737), two years (15.8%,6.2%,9.5%, p = 375), and final evaluation (15.8%,7.7%,14.3%, p = 248). The rate of BI for PBS, IMN, and CPF was 10.5%,0%, and 4.8% (p = 049 PBS/IMN) at one year, 15.8%,0%, and 9.5% (p = 010 PBS/IMN) at two years, and 15.8%,0%, and 14.3% (p = 010 IMN/PBS, p = 013 IMN/CPF) at final evaluation. CONCLUSIONS: Reoperation rate was not significantly different at any time point. However, IMN surgery resulted in the lowest rate of broken implants (zero), statistically significant versus PBS at all time periods and versus CPF at final follow-up. PBS may eventually offer selected advantages for MPHF management, but current data suggests fragility must be thoughtfully considered.

Tumor-to-Tumor Metastasis: Prostate Carcinoma Metastatic to Soft Tissue Sarcoma, a Previously Unreported Event.

Tumor-to-tumor metastasis is an unusual phenomenon wherein one distinct malignancy is present within the substance of another independent tumor. This event is rare, difficult to detect with imaging, and, due to conflicting terminology in the literature, can be challenging to classify. This article reports the first documented case of tumor-to-tumor metastasis involving prostatic adenocarcinoma and myxoid liposarcoma, reviews the available literature for carcinoma metastatic to sarcoma, and discusses the current situation within the context of the established criteria for the classification of combination tumors.

Radical resection of a giant rib osteosarcoma with complex chest wall reconstruction.

INTRODUCTION: Primary rib osteosarcoma is a rare chest wall tumor with variable presentation. Large tumors greater than 10 cm are even rarer and present a challenge for surgical management. PRESENTATION OF CASE: A 61-year-old male with a giant osteosarcoma of the left 2nd rib underwent multidisciplinary management including induction therapy with doxorubicin and cisplatin, followed by en bloc resection with left ribs 1-5, spinous processes of ribs 2-5, small volume lung resection, and chest wall reconstruction with polypropylene mesh and poly methyl methacrylate (PMMA or bone cement). There were no perioperative complications. At 6 months follow-up, the patient remains disease-free. Functional and cosmetic outcome are excellent. DISCUSSION: This 20 cm mass and resection of ribs 1-5 with resulting 25 cm chest wall defect is the largest primary rib osteosarcoma reported in literature. An R0 resection and chest wall reconstruction using polypropylene mesh and bone cement was feasible and safe. CONCLUSION: Giant chest wall defects involving multi-rib resection can be effectively reconstructed with commonly available and inexpensive polypropylene mesh and PMMA to achieve good cosmetic and functional outcomes.

Atypical Lipomatous Tumors: Does Our Inconsistent Terminology Have Patient Repercussions? Results of a Meta-Analysis.

OBJECTIVES: Misnaming low-grade lipomatous tumors poses a clinical and medicolegal challenge, potentially subjecting patients to expensive and unnecessary surgeries. The terms atypical lipomatous tumor (ALT) and "well-differentiated" liposarcoma (WDL) have been used interchangeably in pathology reports, scholarly works and consensus recommendations, creating vagaries between low-virulence extremity tumors and retroperitoneal disease with metastatic potential. METHODS: A systematic review was performed on all studies that reported on the local recurrence rate and metastasis of ALTs and WDLs in living human subjects. Local recurrence and metastases were compared using Fisher's Exact Test. RESULTS: In total, 20 studies evaluated ALTs (n=936), whereas 13 studied WDLs (n=626). Mean follow-up was 6.6±2.0 years (median, 7.0 y). No metastatic disease was observed among ALTs, whereas 15 patients with WDLs (2.7%, P<0.0001) had metastases. The local recurrence rate of ALTs was significantly lower than WDLs after both marginal (15.1%, 141/936 vs. 46.0%, 288/626, P<0.0001) and wide excisions (3.3%, 2/59 in ALT vs. 17.4%, 19/109, P=0.007). CONCLUSIONS: ALT should be reserved for extremity lesions meeting appropriate histopathologic criteria that represent nonmetastatic disease, reducing over-diagnosis, over-treatment, and patient risk.

Pseudomyogenic hemangioendothelioma of skin, bone and soft tissue-a clinicopathological, immunohistochemical, and fluorescence in situ hybridization study.

Pseudomyogenic hemangioendothelioma (PHE) is an uncommon neoplasm with propensity for local recurrence. The tumor mimics epithelioid hemangioendothelioma and epithelioid sarcoma, representing a possible diagnostic pitfall. We investigated the clinicopathological, immunohistochemical, and fluorescence in situ hybridization features of PHEs. Eight cases of PHE were retrieved from our pathology archives. The clinical and outcome information was available in 6 patients. In 6 cases, the tumors were located in the lower limb, whereas the upper limb was involved in 2 cases. Three patients had exclusively bone involvement, and 2 patients had cutaneous tumor only. The tumor was multifocal in 5 cases, of which 2 patients had simultaneous bone and soft tissue involvement. Immunohistochemical stains revealed all tumors to be positive for AE1/AE3 (8/8), ERG (7/7), and FLI-1 (7/7) with preserved INI1 (7/7) expression. Most of the tumors were variably positive for CD31 (7/8), CAM5.2 (2/3), and SMA (4/6). t(7;19)(q22;q13) fusion pattern was detected in 3 cases (5 tumors) with cutaneous and multifocal PHE. In 3 cases, a translocation pattern was detected in a few nuclei but did not meet our laboratory cutoff value. MYC amplification was not detected in any of the 5 cases examined, aiding in ruling out the possibility of angiosarcoma. Four patients underwent excision, and 2 with multifocal tumor required below-knee amputation. Six patients with outcome information were alive and free of disease after a median follow-up of 35 months. We conclude that ancillary techniques can be helpful in differentiating this unusual indolent tumor from potentially aggressive epithelioid hemangioendothelioma, epithelioid sarcoma, and epithelioid angiosarcoma. Long-term follow-up is warranted.

What's Wrong With the Bone? An Overview of Metabolic and Neoplastic Bone Conditions.

The evaluation of any orthopaedic condition often begins with obtaining plain radiographs. Fortuitously, plain radiographs provide surgeons with direct information on the biologic activity and, therefore, the aggressiveness of any bone lesion. More advanced imaging modalities may fail to elucidate the problem and may even obscure the diagnosis. The accurate interpretation of the aggressiveness of a bone lesion on plain radiographs is the first step in establishing a differential diagnosis for any bone lesion and, often, may result in a correct diagnosis without the need for additional imaging studies. A thorough understanding of the radiographic classification of bone lesions will allow surgeons to accurately diagnose and manage metabolic bone disease, benign bone lesions, and malignant bone lesions.

Ossifying fibromyxoid tumor: a study of 6 cases of atypical and malignant variants.

Ossifying fibromyxoid tumors (OFMT) of soft parts are rare, slow-growing tumors that have potential for local recurrence and may metastasize. While OFMT originally was considered benign, several cases of malignant OFMT have been documented. There is no universally accepted risk stratification, although this study emphasizes the importance of utilizing histology, immunohistochemistry and FISH in establishing the diagnosis. Herein, we describe six cases of atypical and malignant OFMT with differences in morphologic features, 5 of which display the proposed morphological criteria for malignancy. The patients were mostly male (M=5, F=1) with an age range of 33-69 years. The tumors arose from the extremities (3 cases), the shoulder (1 case), the head and neck area (1 case), and the paraspinal area (1 case). One tumor had high grade and overtly sarcomatous changes, while another invaded the underlying clavicle. Two cases showed cytological atypia and necrosis. Fluorescence in situ hybridization (FISH) detected rearrangement of the PHF1 gene in 5 cases. All cases were positive for EAAT4 and actin by immunohistochemistry, while negative for desmin. Three tumors were immunoreactive for S100 protein. INI-1 immunohistochemical staining was conserved in all but 2 cases in which a mosaic loss of expression was noted. All but two patients are currently alive and free of disease.

ALDH Activity Correlates with Metastatic Potential in Primary Sarcomas of Bone.

Osteosarcoma (OS), chondrosarcoma (CSA), and Ewings sarcoma (ES) are the most common primary malignancies of bone, and are rare diseases. As with all sarcomas, the prognosis of these diseases ultimately depends on the presence of metastatic disease. Survival is therefore closely linked with the biology and metastatic potential of a particular bone tumor's cells. Here we describe a significant correlation of aldehyde dehydrogenase (ALDH) activity and the presence/absence of distant metastases in ten consecutive cases of human bone sarcomas. Additionally, cultured human CSA cells, which are historically chemo- and radio-resistant, may be sensitive to the ALDH inhibitor, disulfiram. While it is premature to draw broad conclusions from such a small series, the importance of ALDH activity and inhibition in the metastatic potential of primary bone sarcomas should be investigated further.

Does metastasectomy improve survival in skeletal melanoma?

UNLABELLED: Melanoma metastatic to bone carries a poor prognosis with overall median survival in the 4-6 months range. Others have published data that suggest resection of isolated visceral organ metastases improves survival. We conducted a retrospective analysis of 130 cases of stage IV melanoma with pathologically confirmed bony disease. We used Cox regression survival analysis to compare a group of patients who underwent wide resection of metastases with those who received other surgery or were treated nonoperatively. We also compared the three groups against matched historical stage IV melanoma controls to determine differences between expected and observed 1-year overall survival. Median overall survival for the nonoperative (N=80), intralesional (N=32), and resection (N=18) groups was 4.8, 5.1, and 11.8 months, respectively. Cox regression survival analysis confirmed the overall survival benefit resulting from wide resection (hazard ratio 0.53) after correcting for independent predictors of worse survival, such as pathologic spinal compression fracture (hazard ratio 1.68). The observed 1-year overall survival rate in the resection group was nearly double that of matched historical controls (50.0 vs. 24.8%). We present the largest known series of bony melanoma, along with data which suggest that overall survival may be improved in carefully selected patients where all known macroscopic disease can be resected. LEVEL OF EVIDENCE: level III.

Immunohistochemical analysis of expressions of RB1, CDK4, HSP90, cPLA2G4A, and CHMP2B is helpful in distinction between myxofibrosarcoma and myxoid liposarcoma.

The role and diagnostic efficacy of gene and protein products RB1, CDK4, CHMP2B, HSP90, and cPLA2G4A, all previously shown to be involved in tumor genesis and cell proliferation, were examined by immunohistochemical techniques in 32 cases of myxofibrosarcomas and 29 myxoid liposarcomas (all diagnosis had been confirmed by fluorescence in situ hybridization). HSP90 demonstrated strong nuclear and cytoplasmic positivity in all myxoid liposarcoma cases, while only 4 myxofibrosarcomas showed scattered HSP90 positivity. All but 4 cases of myxofibrosarcoma displayed strong positivity for cPLA2G4A, while only 2 myxoid liposarcoma cases were cPLA2G4A positive and both were CHMP2B negative. Overexpression of both cPLA2G4A and CHMP2B also suggested higher tumor grade. In conclusion, HSP90 and cPLA2G4A immunohistochemical stains are useful markers to distinguish myxofibrosarcoma from myxoid liposarcoma.

Proximal femoral replacement in the management of acute periprosthetic fractures of the hip: a competing risks survival analysis.

To examine the mortality and implant survivorship of proximal femoral replacement (PFR), revision total hip arthroplasty (REV) and open reduction internal fixation (ORIF) in the treatment of acute periprosthetic fractures of the proximal femur, we retrospectively reviewed 97 consecutive acute periprosthetic proximal femoral fractures from 2000 to 2010. Three groups were defined: PFR (n=21), REV (n=19), and ORIF (n=57). Outcome measures were all-cause mortality, implant failure, and reoperation. Competing Risks survival analysis of overall mortality during the mean 35-month follow-up showed no statistical difference between the three groups (P=0.65; 12 and 60 month mortality for PFR: 37%, 45%; REV: 16%, 46%; ORIF: 14%, 100%). Implant survival was worse for the PFR group (P=0.03, 12 and 60-month implant failure rate for PFR: 5%, 39%; REV: 7%, 7%; ORIF 2%, 2%). We conclude that PFR as compared with REV or ORIF may have worse medium-term implant survival, primarily due to instability and dislocation.

Inpatient procedures in elderly women: an analysis over time.

OBJECTIVES: To describe inpatient surgical and diagnostic/therapeutic procedures in women ≥65 years old and assess procedure trends over time. STUDY DESIGN: Procedure data for all women ≥65 years was collected using the National Hospital Discharge Survey, a federal dataset drawn from a representative sampling of U.S. inpatient hospitals which includes patient and hospital demographics and ICD-9-CM diagnosis and procedure codes for admissions from 1979 to 2006. MAIN OUTCOME MEASURES: Age-adjusted rates (AAR) per 1000 women were created using 1990 U.S. Census data to compare trends over time. RESULTS: Over 96 million procedures were performed in women age≥65 years from 1979 to 2006. Women age≥65 years constituted 17% of women with ≥1 inpatient procedure in 1979, rising to 32% in 2006. The most common surgical procedures were lower extremity joint replacement, open reduction internal fixation, and cholecystectomy. The most common concurrent diagnosis was femoral neck fracture. Women with femoral neck fracture were more likely to undergo open reduction internal fixation compared to joint replacement. AARs for ORIF fell from 4.3 to 3.2 (p=.02) from 1979 to 2006, while AARs for joint replacement increased from 0.2 to 3.4 (p≤.001, 1979-1988; p=.14, 1990-2006). CONCLUSIONS: The rate of women age≥65 years undergoing inpatient procedures has increased dramatically in the last 30 years. Hip fracture was the most common diagnosis for elderly women, highlighting the impact of osteoporosis and falls and the importance of prevention strategies and optimization of peri-operative care in this population. Further comparative study of hip fracture treatment strategies in this population is needed.

Primary versus secondary distal femoral arthroplasty for treatment of total knee arthroplasty periprosthetic femur fractures.

Current methods of fixing periprosthetic fractures after total knee arthroplasty (TKA) are variable, and include open reduction and internal fixation (ORIF) via plating, retrograde nailing, or revision using standard revision TKA components or a distal femoral arthroplasty (DFA). The purpose of this study is to compare patients who failed plating techniques requiring subsequent revision to DFA to patients who underwent primary DFA. Of the 13 patients (9.2%) who failed primary ORIF, causes included nonunion (53.8%), infection (30.8%), loosening (7.7%), and refracture (7.7%). There were significantly more surgical procedures for ORIF revision to DFA compared to primary DFA. Complications for patients who underwent primary reconstruction with DFAs included extensor mechanism disruption (8.3%), infection (5.6%), and dislocation (2.8%). Primary reconstruction via ORIF is beneficial for preserving bone stock, but primary DFA may be preferred in osteopenic patients, or those at high risk for nonunion.

Treatment solutions are unclear for perimegaprosthetic infections.

BACKGROUND: Infection about a megaprosthesis is a dreaded complication. Treatment options vary from débridement alone to staged revisions, arthrodesis, and amputation. Indications for how to treat this complication are unclear. QUESTIONS/PURPOSES: We therefore determined (1) the incidence of perimegaprosthetic infections, (2) the methods of treatment, (3) the number of patients who failed their original treatment plan, and (4) the characteristics of the infection. METHODS: We retrospectively identified 291 patients who had megaprostheses implanted between 2001 and 2011 and identified all those surgically treated for a perimegaprosthetic infection during that time. We defined a treatment failure as any unplanned reoperation or death due to uncontrolled infection. All patients with failure had a minimum followup of 1 year (mean, 3.3 years; range, 1-8 years). RESULTS: Of the 291 patients, 31 (11%) had subsequent infections. Surgical management varied among irrigation and débridement (n=15), single-stage revisions (n=11), two-stage revisions (n=4), and amputations (n=1). Sixteen patients failed their original treatment plan: 13 required additional surgery and three died. Infections were mostly chronic and single organism with five being methicillin-resistant Staphylococcus aureus. CONCLUSIONS: An 11% incidence of perimegaprosthetic infections is consistent with the increased risk of infection seen in other studies. A variety of surgical methods were employed at our institution and by those contributing to the literature without clear evidence of superiority of one method over another. Given the complicated medical and surgical histories of these patients, individualization in decision making is necessary. LEVEL OF EVIDENCE: Level III, therapeutic study. See Instructions for Authors for a complete description of levels of evidence.